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WO2007070021A1 - Detection of calcifying nano-particles, and associated proteins thereon - Google Patents

Detection of calcifying nano-particles, and associated proteins thereon Download PDF

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Publication number
WO2007070021A1
WO2007070021A1 PCT/US2005/044589 US2005044589W WO2007070021A1 WO 2007070021 A1 WO2007070021 A1 WO 2007070021A1 US 2005044589 W US2005044589 W US 2005044589W WO 2007070021 A1 WO2007070021 A1 WO 2007070021A1
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Prior art keywords
proteins
particle
calcifying nano
factor
disease
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French (fr)
Inventor
E. Olavia Kajander
Katja Aho
Neve Ciftioglu
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Nanobac Pharmaceuticals Inc
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Nanobac Pharmaceuticals Inc
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Priority to PCT/US2005/044589 priority Critical patent/WO2007070021A1/en
Publication of WO2007070021A1 publication Critical patent/WO2007070021A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5082Supracellular entities, e.g. tissue, organisms
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5091Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing the pathological state of an organism
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/54346Nanoparticles
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/52Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Definitions

  • the disclosed invention is generally in the field of calcification and calcifying bodies and specifically in the area of calcifying nano-particles.
  • the present invention discloses methods and compositions for the identication of calcifying nano- particles and protein/calcifying nanoparticles complexes and the correlation of said particles to various diseases. BACKGROUND OF THE INVENTION
  • Calcifying nano-particles are approximately 200 nm in size and appear to multiply in the biological mode, meaning their growth curve has the same characteristics as that of a life form, i.e., certain doubling time (typically around 3 days), plus a lag, a logarithmic, a stationary and even a death phase.
  • the particles are passageable apparently indefinitely in cell culture media (Kajander and Ciftcioglu, Proc. Natl. Acad. Sci. USA 95, 8274 (1998)).
  • the main structural component identified, without question, is bonelike apatite (Kajander and Ciftcioglu, Proc. Natl. Acad. Sci.
  • CNPs have been isolated from kidney stones (Ciftcioglu et al., Kidney Int. 56, 1893 (1999); Khullar et al., Urol. Res. 32, 190 (2004)), gall stones (Wen et al., Chin Med.
  • CNPs have been clearly differentiated from known biological entities: eubacteria, archaea, virus, prions and eukaryotes (Aho and Kajander, J. Clin. Microbiol. 41, 3460 (2003)).
  • CNPs have been shown to form mineral calcium or hydroxy apatite coatings on their surfaces.
  • the hydroxy apatite surface acts an a mineral calcium substrate for the binding of calcium binding proteins (CaBP). Proteins that associate with the CNP
  • CNP/HA complex Hydroxy apatite complex
  • CNP/HA CaBP complex may undergo a conformational change. Subsequently, the CNP/HA CaBP complex may attract or bind proteins that have an affinity to the aforementioned bound CaBPs.
  • Neoeopitope formation is causal for multiple binding by host proteins.
  • Crosslink formation is causal for multiple binding of host protein and stabilizes the structure so that it is stable and can withstand washing steps, for example, detergents, freeze thawing, etc., step involved in assays and storage functions.
  • Copending applications 11/102,798 , 11/180,921, and 11/182,076 disclose methods and compositions for the treatment of CNPs and are incorporated by reference hererin.
  • Commonly assigned patents 6,706,290 (Eradication of Nanobacteria) and 5,135,851 (Culture and Detection Methods for the Sterile Filterable autonomously replicating biological particles) are incorporated by reference herein.
  • the disclosed methods and compositions generally involve detecting one or more proteins present on a calcifying nano-particle. It has been discovered that particular proteins become associated with calcifying nano- particles. This association provides a means for detecting, classifying, analyzing, categorizing, and assessing calcifying nano-particles. Detecting particular proteins while associated with a calcifying nano-particle can be used to indicate the presence and type of calcifying nano-particle, which can be used to indicate the presence of, or disposition to, diseases or conditions. Multiple proteins on a calcifying particle can be detected. The presence or absence of particular proteins and the pattern of the presence and absence of particular proteins can be used to indicate the presence and type of calcifying nano- particle.
  • the disclosed method can involve detecting calcifying particles by detecting one or more proteins on the calcifying particle.
  • the method generally can involve detecting at least one protein on the calcifying particle by binding at least one compound to the protein and detecting the bound compound.
  • Binding a compound to the protein can involve, for example, an antibody.
  • the antibody can be the compound and also can be the means of specific binding of the compound to the protein.
  • a compound can be associated with an antibody with the antibody mediating binding of the compound to the protein. Detecting the bound compound can be accomplished by, for example, detecting the compound directly or indirectly.
  • the compound can be detected using, for example, a microarray, coded beads, flow cytometry, ELISA, mass spectrometry, fluorescence, chemiluminescence, spectrophotometry, chromatography, electrophoresis, or a combination.
  • a microarray coded beads
  • flow cytometry cytometry
  • ELISA electrophoresis
  • fluorescence chemiluminescence
  • spectrophotometry chromatography
  • electrophoresis electrophoresis
  • particular proteins and other components are found on calcifying nano-particles and that detection of such proteins and components can serve to detect, classify, analyze, categorize, and assess calcifying nano-particles.
  • detection of two or more particular proteins in association is indicative and/or characteristic of calcifying nano- particles.
  • detection of a particular protein on a calcifying nano- particle is indicative and/or characteristic of calcifying nano-particles.
  • the presence of the protein on the calcifying nano-particle and/or the identity of combinations of particular proteins serve as identifying characteristics of calcifying nano-particles.
  • Said proteins can undergo a conformational change as result of being associated with calcifying nano-particles.
  • calcium binding proteins will bind to the mineral calcium or hydroxy apaptite coating that surrounds calcifying nano-particles in the circulatory sytem of a mammal.
  • This speficity of conformational changed proteins on the surface of the calcifying nano-particles provides for the specific discovery, detection, classification, analysis, categorization, and assessment of calcifying nano-particles as described herein is useful for diagnosing, assessing, and/or monitoring diseases associated with calcification and calcifying nano- particles, the progress of such diseases, and the progress of treatment of such diseases.
  • Calcifying nano-particles are implicated in and represent a risk factor for disease. For example, as described in Example 1, calcifying nano-particles can stimulate a novel blood coagulation mechanism. This mechanism can explain why thrombosis occurs in diseases associated with calcification and calcifying nano-particles. Because of this discovery, detection, classification, analysis, categorization, and assessment of calcifying nano-particles as described herein is useful for diagnosing, assessing, and/or monitoring diseases associated with calcification and calcifying nano-particles, the progress of such diseases, and the progress of treatment of such diseases.
  • Disclosed is a method for detecting calcifying nano-particles where the method comprises detecting calcifying nano-particles by detecting one or more proteins on the calcifying nano-particles.
  • Also disclosed is a method for detecting one or more proteins where the method comprises detecting one or more proteins on a calcifying nano-particle.
  • the identified proteins identify a disease or condition with which calcifying nano-particles having the identified proteins are related or associated.
  • Also disclosed is a method of assessing the prognosis of a disease or condition where the method comprises identifying one or more proteins on a calcifying nano-particle from a subject.
  • the identified proteins identify calcifying nano-particles that are related to or associated with the prognosis of the disease or condition.
  • Also disclosed is a method of identifying a subject at risk of a disease or condition where the method comprises identifying one or more proteins on a calcifying nano-particle from a subject.
  • the identified proteins identify calcifying nano-particles that are related to or associated with a risk of developing a disease or condition.
  • calcifying nano-particle comprises one or more of the proteins selected from the group consisting of proteins with a Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor XfXa, CDl 4, Prothrombin, Factor DC, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18, Larninin, Antitrypsin, Notch-1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamm
  • proteins that bind to calcium binding proteins may bind to said calcium binding protein/calcifying nano-particles complex including but not limited to Fetuin binding proteins, Thrombin binding proteins, Troponin binding proteins, Tropomyosin binding proteins, GLA Matric binding proteins, Fibrin binding proteins, Kallikrein binding proteins, Factor binding proteins, Matrix metalloprotinease binding proteins, Platelet glycol binding proteins, NF Kappa B binding protein, Factor X binding protein.
  • Table 9 shows representative proteins.
  • compositions comprising a calcifying nano-particle and one or more compounds bound to one or more proteins on the calcifying nano-particle. Also disclosed is a composition of a calcifying nano-particle comprising a hydroxy apatite (mineral calcium phosphate) coating.
  • composition of a calcifying nano-particle comprising said calcifying nanoparticle and a mineral calcium hydroxy apatite coating containing bound proteins that may be conformationally changed. Also disclosed is a method of determining the progress of treatment of a subj ect having calcifying nano-particles, where the method comprises detecting one or more proteins on calcifying nano-particles in a sample from the subject, and repeating the detection in another sample from the subject following treatment. A change in the level, amount, concentration, or a combination of calcifying nano-particles in the subject indicates the progress of the treatment of the subject.
  • compositions comprising apatite and a coating material, where, for example, the coating material limits exposure of the blood of a subject when the composition is in a subject.
  • the present applications may provide for testing of implants of other devices for the detection of CNPs, for example, stents, prosthetics, articificial valves, etc. Artificial devices are commonly covered with calcific biofilms.
  • Also disclosed is a method of testing biocompatibility comprising testing blood coagulation in the absence of anticoagulants. Also disclosed is a method of testing materials that will be exposed to circulating blood for formation of calcific biofilm formation.
  • the term "protein” is meant to include both proteins in there natural state or proteins that have undergone a conformational change, be it primary or primary and secondary hereafter.
  • Calcifying nano-particles can be detected by detecting one or more of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A 5 Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kap ⁇ a B, Osteopontin, Factor X/Xa, CD 14, Prothrombin, Factor IX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin- 1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch- 1, B
  • proteins that bind to calcium binding proteins may bind to said calcium binding protein/calcifying nano-particles complex including but not limited to Fetuin binding proteins, Thrombin binding proteins, Troponin binding proteins, Tropomyosin binding proteins, GLA Matric binding proteins, Fibrin binding proteins, Kallikrein binding proteins, Factor binding proteins, Matrix metalloprotinease binding proteins, Platelet glycol binding proteins, NF Kappa B binding protein, Factor X binding protein.
  • Table 9 shows representative proteins.
  • Calcifying nano-particles can be detected by detecting two or more proteins on the calcifying nano-particles.
  • Calcifying nano-particles can be detected by detecting one or more proteins with a GLA-containing domain.
  • Calcifying nano-particles can be detected by detecting one or more proteins with a calcium binding domain. Calcifying nano-particles can be captured, identified, or both prior to, simultaneous with, or following detection of one or more of the proteins. Capture or identification of the calcifying nano- particle can indicate that the detected proteins are on the calcifying nano-particles. Calcifying nano-particles can be captured by binding at least one compound to one or more of the proteins, wherein the compound is or becomes immobilized. Calcifying nano- particles can be identified by binding at least one compound to one or more of the proteins, wherein the calcifying nano-particles are separated based on the compound. Calcifying nano-particles can be separated by fluorescence activated sorting.
  • One or more of the proteins can be detected by binding at least one compound to the protein and detecting the bound compound. Detection of two or more bound compounds can indicate that the proteins to which the compounds are bound are on the calcifying nano-particle. The two or more compounds can be detected in the same location or at the same time.
  • the compounds can be an antibody, where the antibody is specific for the protein.
  • the calcifying nano-particles can comprise calcium phosphate and one or more of the proteins.
  • the proteins can be detected by detecting any combination of 100 or fewer of the proteins selected from the group consisting of proteins with a Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor X/Xa, CD14, Prothrombin, Factor IX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch- 1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamma-Gla residues, TF
  • the proteins can be detected by detecting any combination of 75 or fewer of the proteins.
  • the proteins can be detected by detecting any combination of 50 or fewer of the proteins.
  • the proteins can be detected by detecting any combination of 25 or fewer of the proteins.
  • the proteins can be detected by detecting any combination of 10 or fewer of the proteins.
  • the proteins can be detected by detecting any combination of 7 or fewer of the proteins.
  • the proteins can be detected by detecting any combination of 3 or fewer of the proteins.
  • the combination of proteins can be detected in the same assay.
  • the combination of proteins can be detected simultaneously.
  • the combination of proteins can be detected on the same calcifying nano-particle.
  • the combination of proteins can be detected on or within the same device.
  • the combination of proteins detected can constitute a pattern of proteins.
  • the pattern can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination.
  • the pattern can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles.
  • the pattern can identify the type of calcifying nano-particles detected.
  • the proteins can be detected by detecting the presence or absence of any combination of 100 or fewer of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-ka ⁇ a B, Osteopontin, Factor XZXa, CD 14, Prothrombin, Factor IX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain,
  • the pattern of the presence or absence of the proteins can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination.
  • the pattern of the presence or absence of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles.
  • the pattern of the presence or absence of the proteins can identify the type of calcifying nano- particles detected.
  • the presence of one or more of the proteins can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination.
  • the presence of one or more of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles.
  • the presence of one or more of the proteins can identify the type of calcifying nano-particles detected.
  • the absence of one or more of the proteins indicates or identifies a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination.
  • the absence of one or more of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles.
  • the absence of one or more of the proteins can identify the type of calcifying nano-particles detected.
  • the proteins can be detected using any suitable composition, apparatus, or technique, for example, a microarray, coded beads, flow cytometry, ELISA, mass spectrometry, fluorescence, chemiluminescence, spectrophotometry, chromatography, electrophoresis, or a combination.
  • the proteins on the calcifying nano-particle can be detected by (a) capturing the calcifying nano-particle, (b) binding a detection compound to one or more of the proteins, and (c) detecting the detection compound.
  • the proteins on the calcifying nano-particle can be detected by (a) binding a detection compound to one or more of the proteins, (b) capturing the calcifying nano-particle, and (c) detecting the detection compound.
  • the calcifying nano-particle can be captured by binding a capture compound to one or more of the proteins, where the capture compound is or becomes immobilized.
  • the proteins to which capture compounds bind can mediate capture, where the detection compound can be bound to one of the proteins, where the calcifying nano-particle can be characterized by determining which proteins mediate capture of the calcifying nano-particle to which the detected detection compound is bound.
  • the capture compound can be bound to one of the proteins, where the detection compounds detected can indicate which of the proteins is present on the calcifying nano-particle, where the calcifying nano-particle can be characterized by which proteins are present on the calcifying nano-particle.
  • the identified proteins can identify the type of calcifying nano-particle.
  • the identified type of calcifying nano-particle can be related to or associated with a disease or condition.
  • the identified proteins can identify a disease or condition with which calcifying nano-particles having the identified proteins are related or associated.
  • the identified proteins can identify a disease or condition that is caused by calcifying nano- particles having the identified proteins.
  • the identified proteins can identify a disease or condition in which calcifying nano-particles having the identified proteins are produced.
  • Subjects in which pathological thrombosis can occur via apatite-mediated clotting are useful targets for the disclosed methods.
  • Such subjects can include (1) Patients with vulnerable plaque rupture exposing atheroma calcification; (2) Patients undergoing angioplasty or heart-lung machine perfusion; (3) Patients with massive bone fractures or dislocated implants releasing potentially apatite particles; (4) Patients with implants, catheters, wires or stents subject to calcium encrustation; (5) Cancer patients with soft tissue calcification; and (6) Healthy or sick people with CNPs in their blood or positive calcification scores in arteries.
  • the composition can comprise a calcifying nano-particle and one or more compounds bound to two or more proteins on the calcifying nano-particle.
  • the compound can comprise an antibody, where the antibody is specific for the protein.
  • the compound can block the calcifying nano-particle.
  • FIGS. IA- IE are diagrams showing an example of Surface Antigen Pattern Immunoassay (SAPIA).
  • SAPIA Surface Antigen Pattern Immunoassay
  • Figures 2A and 2B are graphs of levels of signal generated for various proteins in SAPIA performed on positive ( Figure 2A) and negative ( Figure 2B) serum and plasma samples showing same levels in serum and plasma.
  • Figure 3 is a scatterplot of SAPIA results for clotting matrix GLA proteins, fibrinogen and tissue factor, and CNP capture ELISA results.
  • Figure 4 is a graph of levels of signal generated for various proteins in SAPIA showing the presence of pro-thrombin fragments and oesteocalcin in CNPsas measured by sepia.
  • Figures 5 A and 5B are graphs of prothrombin activation on apatite using bovine ( Figure 5A) and human ( Figure 5B) prothrombin.
  • Figure 6 is a graph of whole blood clotting times for various materials using glass slide test.
  • Figure 7 is a diagram of apatite-mediated clotting pathway.
  • Figure 8 is a diagram of a model for conformational changes caused by apatite/blood calcium binding as exemplified by prothrombin.
  • Figure 9 is a diagram of formation of fibrin in response to thrombotic event due to CNPs how thrombin bound to apatite surface activates formation of fibrin.
  • Figures 1OA shows boxplots of individual disease states.
  • Figures 1OB shows boxplots of individual proteins correlating with disease.
  • Figure 1OC shows protein stip plots.
  • Figure 11 is a graph of clinomics samples for 15 diseases associated with CNPs. Marker values can be obtained from the disease.
  • Figure 12 is a graph depicting urine expression showing physiological differentiations of various CNP isolates 99m Tc.
  • Figure 13 is a graph of CNP antigen (U/niL) for Pacreatitis, Rheumatoid Arthritis and Cholecystitis.
  • Figure 14 is a boxplot of biomarkers for negative endometrioid adenocarcinoma.
  • Figure 15 is a boxplot for biomarkers for positive endometrioid adenocarcinoma.
  • Figure 16 is scatterplot of markers for aortic data.
  • Figure 17 is a scatterplot of markers for arthritis data.
  • Figure 18 is a scatterplot of markers for cholecystitis data.
  • Figure 19 is a scatterplot of markers for endometrioid data.
  • Figure 20 is a- scatterplot of markers for kidney stones data.
  • Figure 21 is a scatterplot of markers for Parkinson's data.
  • Figure 22 is a scatterplot of markers for prostate data.
  • Figure 23 is a scatterplot of markers for prostatitis data.
  • the disclosed method and compositions may be understood more readily by reference to the following detailed description of particular embodiments and the Example included therein and to the Figures and their previous and following description.
  • the disclosed methods and compositions generally involve detecting one or more proteins present on a calcifying nano-particle. It has been discovered that particular proteins become associated with calcifying nano- particles. This association provides a means for detecting, classifying, analyzing, categorizing, and assessing calcifying nano-particles.
  • Detecting particular proteins while associated with a calcifying nano-particle can be used to indicate the presence and type of calcifying nano-particle, which can be used to indicate the presence of, or disposition to, diseases or conditions.
  • Multiple proteins on a calcifying particle can be detected. Proteins may experience a conformational change resultant from association and/or binding to the califying nano-particle. Proteins associated with calcifying nano-particles may undergo secondary conformational changes. Proteins may bind to proteins associated to calcifying nanoparticles.
  • the presence or absence of particular proteins and the pattern of the presence and absence of particular proteins can be used to indicate the presence and type of calcifying nano-particle.
  • the disclosed method can involve detecting calcifying particles by detecting one or more proteins on the calcifying particle.
  • the method generally can involve detecting at least one protein on the calcifying particle by binding at least one compound to the protein and detecting the bound compound.
  • Binding a compound to the protein can involve, for example, an antibody.
  • the antibody can be the compound and also can be the means of specific binding of the compound to the protein.
  • a compound can be associated with an antibody with the antibody mediating binding of the compound to the protein.
  • Detecting the bound compound can be accomplished by, for example, detecting the compound directly or indirectly.
  • the compound can be detected using, for example, a microarray, coded beads, flow cytometry, ELISA, mass spectrometry, fluorescence, chemiluminescence, spectrophotometry, chromatography, electrophoresis, or a combination.
  • compositions and methods are known for the detection of analytes and such can be used in and with the disclosed compositions and methods for the detection of calcifying nano-particles and proteins on calcifying nano- particles. Some such compositions and methods are described herein and others are known to those of skill in the art.
  • Detection of two or more proteins associated with calcifying nanoparticles enables the generation of a patterns that are useful for diagnosing, assessing, and/or monitoring diseases.
  • the origin and activity of said detected proteins is usefull in the determination of a potential or active disease state in the host.
  • Calcifying nano-particles are implicated in and represent a risk factor for disease. For example, as described in the Example, calcifying nano-particles can stimulate a novel blood coagulation mechanism. This mechanism can explain why thrombosis occurs in diseases associated with calcification and calcifying nano-particles. Because of this discovery, detection, classification, analysis, categorization, and assessment of calcifying nano-particles as described herein is useful for diagnosing, assessing, and/or monitoring diseases associated with calcification and calcifying nano-particles, the progress of such diseases, and the progress of treatment of such diseases.
  • calcifying nano-particle comprises one or more of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kap ⁇ a B, Osteopontin, Factor XIXa, CDU, Prothrombin, Factor JX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin- 1 5 B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch-1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer Factor V, gamma
  • composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that collects said calcium binding proteins.
  • a compositon comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that has calcium binding proteins associated thereon and proteins that bind to said calcium binding proteins.
  • compositions comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that has calcium binding proteins associated thereon wherein said calcium binding proteins undergo a primary conformation change as a result of said association
  • composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating containing bound calcium binding binding proteins that may experience conformational changes and wherein secondary bound proteins thereon experience conformational changes.
  • composition comprising a calcifying nano-particle and one or more compounds bound to one or more proteins on the calcifying nano-particle.
  • compositions comprising apatite and a coating material, where, for example, the coating material limits exposure of the blood of a subject when the composition is in a subj ect.
  • the composition can comprise a calcifying nano-particle and one or more compounds bound to two or more proteins on the calcifying nano-particle.
  • the compound can comprise an antibody, where the antibody is specific for the protein.
  • the compound can block the calcifying nano-particle.
  • the disclosed method can make use of compounds that can bind to calcifying nano-particles, such as compounds that can bind proteins on calcifying nano-particles.
  • Detection compounds and capture compounds are examples of such compounds.
  • Compounds for use in the disclosed methods can be any compound, molecule, material or substance that can bind to a calcifying nano-particle and/or a protein on a calcifying nano- particle. It is preferred that the compound bind specifically to the calcifying nano-particle or protein. Such specificity allows detection and identification of calcifying nano-particles and proteins.
  • Useful compounds include antibodies and molecules that can bind to proteins on calcifying nano-particles such as ligands, substrates, proteins, cofactors, coenzymes.
  • Useful compounds include compounds, such as antibodies, that can bind to proteins with a Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor XJXa, CD 14, Prothrombin, Factor IX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch-1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamma-Gla residues, TF-VIIa, Complement 3c3, Comp
  • the disclosed compounds can be used for detection and capture of calcifying nano-particles and/or proteins on calcifying nano-particles.
  • detecting compounds can be used for detection and capture compounds can be used for capture of calcifying nano-particles and/or proteins on calcifying nano-particles.
  • Detection and identification of calcifying nano-particles and proteins on calcifying nano-particles can be facilitated by including labels on the disclosed compounds. Useful labels and their use are described elsewhere herein. Detection of compounds bound to calcifying nano-particles and/or proteins on calcifying nano-particles indicates the presence of the bound calcifying nano-particles and/or proteins on calcifying nano-particles.
  • the disclosed compounds can be detected, for example, via labels on the compounds, by direct detection of the compounds (via an intrinsic feature of the compounds, for example), or by binding a secondary compound to the primary compound and detecting the secondary compound.
  • the secondary compound can include a label.
  • labels can be used.
  • labels can be incorporated into, coupled to, or associated with, compounds, detection compound, capture compound (such as compounds to be bound to proteins).
  • a label can include, for example, a fluorescent dye, a member of binding pair, such as biotin/streptavidin, a metal (e.g., gold), or an epitope tag that can specifically interact with a molecule that can be detected, such as by producing a colored substrate or fluorescence.
  • labels can be detected using nuclear magnetic resonance, electron paramagnetic resonance, surface enhanced raman scattering, surface plasmon resonance, fluorescence, phosphorescence, chemiluminescence, resonance raman, microwave, photometry, mass spectrometry, or a combination.
  • Substances suitable for detectably labeling proteins include, for example, fluorescent dyes (also known herein as fluorochromes and fluorophores), chromophores, and enzymes that react with colorometric substrates (e.g., horseradish peroxidase).
  • fluorescent dyes also known herein as fluorochromes and fluorophores
  • chromophores and enzymes that react with colorometric substrates (e.g., horseradish peroxidase).
  • colorometric substrates e.g., horseradish peroxidase
  • each protein can be associated with a distinct label compound for simultaneous and/or multiplex detection.
  • Labels can be detected using a detection device or apparatus suitable for the label to be detected, such as a fluorimeter, spectrophotomer, or mass spectrometer, the presence of a signal indicating the presence of the corresponding protein.
  • Fluorophores are compounds or molecules that luminesce. Typically fluorophores absorb electromagnetic energy at one wavelength and emit electromagnetic energy at a second wavelength. Representative fluorophores include, but are not limited to, 1,5 IAEDANS; 1,8-ANS; 4- Methylumbelliferone; 5-carboxy-2,7-dichlorofluorescein; 5- Carboxyfluorescein (5-FAM); 5-Carboxynapthofluorescein; 5- Carboxytetramethylrhodamine (5-TAMRA); 5 -Hydroxy Tryptamine (5-HAT); 5-ROX (carboxy-X-rhodamine); 6-Carboxyrhodamine 6G; 6-CR 6G; 6- JOE; 7-Amino-4- methylcoumarin; 7-Aminoactmomycm D (7 -AAD); 7-Hydroxy-4- 1 methylcoumariii; 9- Amino-6-chloro-2-methoxyacridine (ACMA
  • Ethidium homodimer-1 (EthD-1); Euchrysin; EukoLight; Europium (111) chloride; EYFP; Fast Blue; FDA; Feulgen (Pararosaniline); FIF (Formaldehyd Induced Fluorescence); FITC; Flazo Orange; Fluo-3; Fluo-4; Fluorescein (FITC); Fluorescein Diacetate; Fluoro- Emerald; Fluoro-Gold (Hydroxystilbamidine); Fluor-Ruby; FluorX; FM 1-43TM; FM 4-46; Fura RedTM (high pH); Fura RedTM/Fluo-3 ; Fura-2; Fura-2/BCECF; Genacryl Brilliant Red B; Genacryl Brilliant Yellow 10GF; Genacryl Pink 3G; Genacryl Yellow 5GF; GeneBlazer; (CCF2); GFP (S65T); GFP red shifted (rsGFP); GFP wild type' non-UV excitation (wtGFP); GFP wild type, UV excitation (wtGF
  • labels include molecular or metal barcodes, mass labels, and labels detectable by nuclear magnetic resonance, electron paramagnetic resonance, surface enhanced raman scattering, surface plasmon resonance, fluorescence, phosphorescence, chemiluminescence, resonance raman, microwave, photometry, mass spectrometry, or a combination.
  • Mass labels are compounds or moieties that have, or which give the labeled component, a distinctive mass signature in mass spectroscopy. Mass labels are useful when mass spectroscopy is used for detection.
  • Preferred mass labels are peptide nucleic acids and carbohydrates.
  • Combinations of labels can also be useful. For example, color- encoded microbeads having, for example, 256 unique combinations of labels, are useful for distinguishing numerous components. For example, 256 different ligator-detectors can be uniquely labeled and detected allowing multiplexing and automation of the disclosed method.
  • Metal barcodes a form of molecular barcode, can be, for example, 30-300 nm diameter by 400-4000 nm multilayer multi metal rods. These rods can be constructed by electrodeposition into an alumina mold, then the alumina is removed leaving these small multilayer objects behind.
  • the system can have multiple zones encoded using multiple different metals where the metals have different reflectivity and thus appear lighter or darker in an optical microscope depending on the metal. For example, up to 12 zones can be encoded in up to 7 different metals. This allows practically unlimited identification codes.
  • the metal bars can be coated with glass or other material, which can facilitate attachment of the bars to compounds to be labeled. The bars can be identified from the light dark pattern of the barcode.
  • Epitopes can be used as labels.
  • Epitopes (that is, a portion of a molecule to which an antibody binds) can be composed of sugars, lipids or amino acids.
  • Epitope tags are useful for the labeling and detection of proteins when an antibody to the protein is not available. Due to their small size, they are unlikely to affect the tagged protein's biochemical properties.
  • Epitope tags generally range from 10 to 15 amino acids long and are designed to create a molecular handle for the protein.
  • An epitope tag can be placed anywhere within the protein, but typically they are placed on either the amino or carboxyl terminus to minimize any potential disruption in tertiary structure and thus function of the protein. Any short stretch of amino acids known to bind an antibody could become an epitope tag.
  • Useful epitope tags include c-myc (a 10 amino acid segment of the human protooncogene myc), haemoglutinin (HA) protein, His ⁇ , Green flourescent protein (GFP), digoxigenin (DIG), and biotin. Flourescent dyes, such as those described herein, can also be used as epitope tags.
  • Calcifying nano-particles and proteins on calcifying nano-particles can be any from any source, such as an animal.
  • the disclosed method is performed using a sample that contains (or is suspected of containing) calcifying nano-particles.
  • a sample can be any sample of interest.
  • the source, identity, and preparation of many such samples are known.
  • the sample can be, for example, a sample from one or more cells, tissue, or bodily fluids such as blood, urine, semen, lymphatic fluid, cerebrospinal fluid, or amniotic fluid, or other biological samples, such as tissue culture cells, buccal swabs, mouthwash, stool, tissues slices, and biopsy aspiration.
  • Types of useful samples include blood samples, urine samples, semen samples, lymphatic fluid samples, cerebrospinal fluid samples, amniotic fluid samples, biopsy samples, needle aspiration biopsy samples, cancer samples, tumor samples, tissue samples, cell samples, cell lysate samples, and/or crude cell lysate samples.
  • the sample can be from any organism of interest that contains or is suspected of containing calcifying nano-particles.
  • the sample can be animal, non-human animals, vertebrate, non-human vertebrate, invertebrate, insect, amphibian, avian, reptilian, fish, mammalian, non-human mammalian, rodent, farm animal, domesticated animal, bovine, porcine, murine, feline, canine, or human.
  • the term subject can refer to any animal or any member of any subgroup or classification of animal, including those listed above and elsewhere herein.
  • patient can refer to any animal under care or treatment, such as a veterinary patient or human patient. D. Solid Supports
  • Solid supports are solid-state substrates or supports with which molecules, such as analytes and analyte binding molecules, can be associated.
  • Analytes such as calcifying nano-particles and proteins, can be associated with solid supports directly or indirectly.
  • analytes can be directly immobilized on solid supports.
  • Analyte capture agents such a capture compounds, can also be immobilized on solid supports.
  • a preferred form of solid support is an array.
  • Another form of solid support is an array detector.
  • An array detector is a solid support to which multiple different capture compounds or detection compounds have been coupled in an array, grid, or other organized pattern.
  • Solid-state substrates for use in solid supports can include any solid material to which molecules can be coupled.
  • Solid-state substrates can have any useful form including thin film, membrane, bottles, dishes, fibers, woven fibers, shaped polymers, particles, beads, microparticles, or a combination.
  • Solid-state substrates and solid supports can be porous or non-porous.
  • a preferred form for a solid-state substrate is a microtiter dish, such as a standard 96-well type.
  • a multiwell glass slide can be employed that normally contain one array per well. This feature allows for greater control of assay reproducibility, increased throughput and sample handling, and ease of automation.
  • Different compounds can be used together as a set.
  • the set can be used as a mixture of all or subsets of the compounds used separately in separate reactions, or immobilized in an array.
  • Compounds used separately or as mixtures can be physically separable through, for example, association with or immobilization on a solid support.
  • An array can include a plurality of compounds immobilized at identified or predefined locations on the array. Each predefined location on the array generally can have one type of component (that is, all the components at that location are the same). Each location will have multiple copies of the component.
  • the spatial separation of different components in the array allows separate detection and identification of calcifying nano-particles and proteins. Although preferred, it is not required that a given array be a single unit or structure.
  • the set of compounds may be distributed over any number of solid supports.
  • each compound may be immobilized in a separate reaction tube or container, or on separate beads or microparticles.
  • Different modes of the disclosed method can be performed with different components (for example, different compounds specific for different proteins) immobilized on a solid support.
  • Some solid supports can have capture compounds, such as antibodies, attached to a solid-state substrate.
  • capture compounds can be specific for calcifying nano- particles or a protein on calcifying nano-particles. Captured calcifying nano-particles or proteins can then be detected by binding of a second, detection compound, such as an antibody.
  • the detection compound can be specific for the same or a different protein on the calcifying nano-particle.
  • Immobilization can be accomplished by attachment, for example, to aminated surfaces, carboxylated surfaces or hydroxylated surfaces using standard immobilization chemistries.
  • attachment agents are cyanogen bromide, succinimide, aldehydes, tosyl chloride, avidin-biotin, photocrosslinkable agents, epoxides and maleimides.
  • a preferred attachment agent is the heterobifimctional cross-linker N-[ ⁇ - Maleimidobutyryloxy] succinimide ester (GMBS).
  • Antibodies can be attached to a substrate by chemically cross-linking a free amino group on the antibody to reactive side groups present within the solid-state substrate.
  • antibodies may be chemically cross-linked to a substrate that contains free amino, carboxyl, or sulfur groups using glutaraldehyde, carbodiimides, or GMBS, respectively, as cross-linker agents.
  • aqueous solutions containing free antibodies are incubated with the solid-state substrate in the presence of glutaraldehyde or carbodiimide.
  • a preferred method for attaching antibodies or other proteins to a solid-state substrate is to functionalize the substrate with an amino- or thiol-silane, and then to activate the functionalized substrate with a homobifunctional cross-linker agent such as (Bis-sulfo-succinimidyl suberate (BS 3 ) or a heterobifunctional cross-linker agent such as GMBS.
  • a homobifunctional cross-linker agent such as (Bis-sulfo-succinimidyl suberate (BS 3 ) or a heterobifunctional cross-linker agent such as GMBS.
  • Thiol- derivatized slides are activated by immersing in a 0.5 mg/ml solution of GMBS in 1% dimethylformamide, 99% ethanol for 1 hour at room temperature. Antibodies or proteins are added directly to the activated substrate, which are then blocked with solutions containing agents such as 2% bovine serum albumin, and air-dried. Other standard immobilization chemistries are known by those of skill in the art.
  • Each of the components (compounds, for example) immobilized on the solid support preferably is located in a different predefined region of the solid support.
  • Each of the different predefined regions can be physically separated from each other of the different regions.
  • the distance between the different predefined regions of the solid support can be either fixed or variable. For example, in an array, each of the components can be arranged at fixed distances from each other, while components associated with beads will not be in a fixed spatial relationship. In particular, the use of multiple solid support units (for example, multiple beads) will result in variable distances.
  • Components can be associated or immobilized on a solid support at any density. Components preferably are immobilized to the solid support at a density exceeding 400 different components per cubic centimeter.
  • Arrays of components can have any number of components. For example, an array can have at least 1,000 different components immobilized on the solid support, at least 10,000 different components immobilized on the solid support, at least 100,000 different components immobilized on the solid support, or at least 1,000,000 different components immobilized on the solid support.
  • kits for detecting calcifying nano-particles the kit comprising one or more detection compounds, one or more capture compounds, and one or more solid supports.
  • the kits also can contain one or more buffers.
  • mixtures formed by performing or preparing to perform the disclosed method For example, disclosed are mixtures comprising a calcifying nano-particle, a detection compound, and a capture compound.
  • performing the method creates a number of different mixtures. For example, if the method includes 3 mixing steps, after each one of these steps a unique mixture is formed if the steps are performed separately.
  • a mixture is formed at the completion of all of the steps regardless of how the steps were performed.
  • the present disclosure contemplates these mixtures, obtained by the performance of the disclosed methods as well as mixtures containing any disclosed reagent, composition, or component, for example, disclosed herein.
  • Systems useful for performing, or aiding in the performance of, the disclosed method.
  • Systems generally comprise combinations of articles of manufacture such as structures, machines, devices, and the like, and compositions, compounds, materials, and the like. Such combinations that are disclosed or that are apparent from the disclosure are contemplated.
  • systems comprising a calcifying nano-particle, a detection compound, and a solid support.
  • Data structures used in, generated by, or generated from, the disclosed method.
  • Data structures generally are any form of data, information, and/or objects collected, organized, stored, and/or embodied in a composition or medium.
  • the disclosed method, or any part thereof or preparation therefor, can be controlled, managed, or otherwise assisted by computer control.
  • Such computer control can be accomplished by a computer controlled process or method, can use and/or generate data structures, and can use a computer program. These include such techniques as neural network that may quickly analyze and interpret data for clinical diagnosis and interpreations to indicated a disease state.
  • Such computer control, computer controlled processes, data structures, and computer programs are contemplated and should be understood to be disclosed herein. Uses
  • the disclosed methods and compositions are applicable to numerous areas including, but not limited to, detecting, analyzing and assessing the significance of calcifying nano-particles.
  • Other uses include, for example, detecting one or more proteins on a calcifying nano-particle, characterizing a calcifying nano-particle, diagnosing a disease or condition, assessing the prognosis of a disease or condition, identifying a subject at risk of a disease or condition, determining the progress of treatment of a subject having calcifying nano-particles, testing biocompatibility comprising testing blood coagulation in the absence of anticoagulants, and testing materials that will be exposed to circulating blood for formation of calcific biofilm formation.
  • Other uses are disclosed, apparent from the disclosure, and/or will be understood by those in the art.
  • the disclosed methods generally involve detecting one or more proteins present on a calcifying nano-particle. It has been discovered that particular proteins become associated with calcifying nano-particles. This association provides a means for detecting, classifying, analyzing, categorizing, and assessing calcifying nano- particles. Detecting particular proteins while associated with a calcifying nano-particle can be used to indicate the presence and type of calcifying nano-particle, which can be used to indicate the presence of, or disposition to, diseases or conditions. Multiple proteins on a calcifying particle can be detected. The presence or absence of particular proteins and the pattern of the presence and absence of particular proteins can be used to indicate the presence and type of calcifying nano-particle.
  • the disclosed method can involve detecting calcifying particles by detecting one or more proteins on the calcifying particle.
  • the method generally can involve detecting at least one protein on the calcifying particle by binding at least one compound to the protein and detecting the bound compound.
  • Binding a compound to the protein can involve, for example, an antibody.
  • the antibody can be the compound and also can be the means of specific binding of the compound to the protein.
  • a compound can be associated with an antibody with the antibody mediating binding of the compound to the protein. Detecting the bound compound can be accomplished by, for example, detecting the compound directly or indirectly.
  • the compound can be detected using, for example, a microarray, coded beads, coated beads, flow cytometry, ELISA, mass spectrometry, fluorescence, chemiluminescence, spectrophotometry, chromatography, electrophoresis, or a combination.
  • Detection and identification of calcifying nano-particles and proteins on calcifying nano-particles can be facilitated by including labels on the disclosed compounds. Useful labels and their use are described elsewhere herein. Detection of compounds bound to calcifying nano-particles and/or proteins on calcifying nano-particles indicates the presence of the bound calcifying nano-particles and/or proteins on calcifying nano- particles.
  • the disclosed compounds can be detected, for example, via labels on the compounds, by direct detection of the compounds (via an intrinsic feature of the compounds, for example), or by binding a secondary compound to the primary compound and detecting the secondary compound.
  • the secondary compound can include a label.
  • Disclosed is a method for detecting calcifying nano-particles where the method comprises detecting calcifying nano-particles by detecting one or more proteins on the calcifying nano-particles.
  • composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that collects said calcium binding proteins.
  • a compositon comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that has calcium binding proteins associated thereon and proteins that bind to said calcium binding proteins.
  • a hydroxy apatite calcium phosphate mineral
  • composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that has calcium binding proteins associated thereon wherein said calcium binding proteins undergo a primary conformation change as a result of said association
  • a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that has calcium binding proteins associated thereon wherein said calcium binding proteins undergo a primary conformation change as a result of said association
  • composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating containing bound calcium binding binding proteins that may experience conformational changes and s secondary bound proteins thereon that experience conformational changes.
  • a hydroxy apatite calcium phosphate mineral
  • Also disclosed is a method for detecting one or more proteins comprising detecting one or more proteins on a calcifying nano-particle. Also disclosed is a method of characterizing a calcifying nano-particle, where the method comprises identifying one or more proteins on a calcifying nano-particle.
  • Also disclosed is a method of diagnosing a disease or condition where the method comprises identifying one or more proteins on a calcifying nano-particle from a subject.
  • the identified proteins identify a disease or condition with which calcifying nano-particles having the identified proteins are related or associated.
  • Also disclosed is a method of assessing the prognosis of a disease or condition where the method comprises identifying one or more proteins on a calcifying nano-particle from a subject.
  • the identified proteins identify calcifying nano-particles that are related to or associated with the prognosis of the disease or condition.
  • Also disclosed is a method of identifying a subject at risk of a disease or condition where the method comprises identifying one or more proteins on a calcifying nano-particle from a subject.
  • the identified proteins identify calcifying nano-particles that are related to or associated with a risk of developing a disease or condition.
  • a method of determining the progress of treatment of a subj ect having calcifying nano-particles where the method comprises detecting one or more proteins on calcifying nano-particles in a sample from the subject, and repeating the detection in another sample from the subject following treatment.
  • a change in the level, amount, concentration, or a combination of calcifying nano-particles in the subject indicates the progress of the treatment of the subj ect.
  • Also disclosed is a method of testing biocompatibility comprising testing blood coagulation in the absence of anticoagulants.
  • Calcifying nano-particles can be detected by detecting one or more of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kap ⁇ a B, Osteopontin, Factor X/Xa, CD 14, Prothrombin, Factor IX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin- 1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch- 1, BSA, LBP, PTX3, Complement C5, Fibrin
  • Calcifying nano-particles can be detected by detecting two or more proteins on the calcifying nano-particles. Calcifying nano-particles can be detected by detecting one or more proteins with a GLA-containing domain. Calcifying nano-particles can be detected by detecting one or more proteins with a calcium binding domain. Calcifying nano- particles can be captured, identified, or both prior to, simultaneous with, or following detection of one or more of the proteins. Capture or identification of the calcifying nano- particle can indicate that the detected proteins are on the calcifying nano-particles. Calcifying nano-particles can be captured by binding at least one compound to one or more of the proteins, wherein the compound is or becomes immobilized. Calcifying nano- particles can be identified by binding at least one compound to one or more of the proteins, wherein the calcifying nano-particles are separated based on the compound. Calcifying nano-particles can be separated by fluorescence activated sorting.
  • One or more of the proteins can be detected by binding at least one compound to the protein and detecting the bound compound. Detection of two or more bound compounds can indicate that the proteins to which the compounds are bound are on the calcifying nano-particle. The two or more compounds can be detected in the same location or at the same time.
  • the compounds can be an antibody, where the antibody is specific for the protein.
  • the calcifying nano-particles can comprise calcium phosphate and one or more of the proteins.
  • the proteins can be detected by detecting any combination of 10 or fewer of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappaB, Osteopontin, Factor X/Xa, CD 14, Prothrombin, Factor FX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch- 1 , BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamma-Gla residues, TF-VI
  • Said proteins may or may not undergo conformational changes.
  • the proteins can be detected by detecting any combination of 7 or fewer of the proteins.
  • the proteins can be detected by detecting any combination of 5 or fewer of the proteins.
  • the proteins can be detected by detecting any combination of 3 or fewer of the proteins.
  • the combination of proteins can be detected in the same assay.
  • the combination of proteins can be detected simultaneously.
  • the combination of proteins can be detected on the same calcifying nano-particle.
  • the combination of proteins can be detected on or within the same device.
  • the combination of proteins detected can constitute a pattern of proteins.
  • the pattern can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination.
  • the pattern can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles.
  • the pattern can identify the type of calcifying nano-particles detected.
  • Disease associated with patholical clarification include, but are not limited to for example, heart or circulatory diseases such as Arteriosclerosis, Atherosclerosis, Coronary Heart Disease, Chronic Heart Failure, Valve Calcifications, Arterial Aneurysms, Calcific Aortic Stenosis, Transient Cerebral Ischemia, Stroke, Peripheral Vascular Disease, Monckeberg's Disease, Vascular Thrombosis; Dental Diseases such as Dental Plaque, Gum Disease (dental pulp stones), calcification of the dentinal papilla, and Salivary Gland Stones; Chronic Infection Syndromes such as Chronic Fatigue Syndrome; Kidney and Bladder Stones, Gall Stones, Pancreas and Bowel Diseases such as Pancreatic Duct Stones, Crohn's Disease, Colitis Ulcerosa; Blood disorders
  • Ear Diseases such as Otosclerosis, Degeneration of Otoliths and Symptoms from the Vestibular Organ and Inner Ear (Vertigo and Tinnitus); Thyroglossal cysts, Thyroid Cysts, Ovarian Cysts; Cancer such as Meningiomas, Breast Cancer, Prostate Cancer, Thyroid Cancer, Serous Ovarian Adenocarcinoma; Skin diseases such as Calcinosis Cutis, Skin Stones, Calciphylaxis, Psoriasis, Eczema, Lichen Ruber Planus or Lichen Simple Cysts;, Choroid Plexus Calcification, Neuronal Calcification, Calcification of the FaIx Cerebri, Calcification of the Intervertebral Cartilage or Disc, Intercranial or Cerebral Calcification, Rheumatoid Arthritis, Calcific Tenditis, Oseoarthritis, Fibromyalg
  • the proteins can be detected by detecting the presence or absence of any combination of 10 or fewer of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor X/Xa, CDU, Prothrombin, Factor FX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch- 1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamma-Gla residues,
  • proteins that bind to calcium binding proteins may bind to said calcium binding protein/calcifying nano-particles complex including but not limited to Fetuin binding proteins, Thrombin binding proteins, Troponin binding proteins, Tropomyosin binding proteins, GLA Matric binding proteins, Fibrin binding proteins, Kallikrein binding proteins, Factor binding proteins, Matrix metalloprotinease binding proteins, Platelet glycol binding proteins, NF Kappa B binding protein, Factor X binding protein.
  • Table 9 shows representative proteins. Said proteins may or may not undergo conformational changes.
  • the pattern of the presence or absence of the proteins can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination.
  • the pattern of the presence or absence of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles.
  • the pattern of the presence or absence of the proteins can identify the type of calcifying nano- particles detected.
  • the presence of one or more of the proteins can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination.
  • the presence of one or more of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles.
  • the presence of one or more of the proteins can identify the type of calcifying nano-particles detected.
  • the absence of one or more of the proteins indicates or identifies a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination.
  • the absence of one or more of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles.
  • the absence of one or more of the proteins can identify the type of calcifying nano-particles detected.
  • Diseases associated with CNPs and pathological calcification include, but are not limimted to, for example, heart or circulatory diseases such as Arteriosclerosis, Atherosclerosis, Coronary Heart Disease, Chronic Heart Failure, Valve Calcifications, Arterial Aneurysms, Calcific Aortic Stenosis, Transient Cerebral Ischemia, Stroke, Peripheral Vascular Disease, Monckeberg's Disease, Vascular Thrombosis; Dental
  • Ear Diseases such as Otosclerosis, Degeneration of Otoliths and Symptoms from the Vestibular Organ and Inner Ear (Vertigo and Tinnitus); Thyroglossal cysts, Thyroid Cysts, Ovarian Cysts; Cancer such as Meningiomas, Breast Cancer, Prostate Cancer, Thyroid Cancer, Serous Ovarian Adenocarcinoma; Skin diseases such as Calcinosis Cutis, Skin Stones, Calciphylaxis, Psoriasis, Eczema, Lichen Ruber Planus or Lichen Simple Cysts;, Choroid Plexus Calcification, Neuronal Calcification, Calcification of the FaIx Cerebri, Calcification of the Intervertebral Cartilage or Disc, Intercranial or Cerebral Calcification, Rheumatoid Arthritis, Calcific Tenditis, Oseoarthritis, Fibromyalgia, Bone Spurs, Diff
  • the proteins can be detected using any suitable composition, apparatus, or technique, for example, a microarray, coded beads, flow cytometry, ELISA, mass spectrometry, fluorescence, chemiluminescence, spectrophotometry, chromatography, electrophoresis, or a combination.
  • the disclosed method can use an immunassy detecting approximagtely 100 or fewer difrrerent antigens on the same particles using only one tracer antibody for all of said detected target antigens or epitopes. Thereby utilitizing only one standard curve to provide quantitation of the target antigens and/or epitopes (focused on the use of the antibody).
  • the disclosed method is especially suitable for biogenic particles, such as CNPs, due to stable surface structure due to crosslinking of proteins and binding to the HA.
  • the disclosed method is not limited to CNPs.
  • the disclosed method can be utilitzed with viruses, spores, bacteria with stable capsules or similar stable substrate, microparticles in blood, plasma, and the like.
  • the particles may be captured using antibodies from any source or based on chemical regions from any source.
  • the proteins on the calcifying nano-particle can be detected by (a) capturing the calcifying nano-particle, (b) binding a detection compound to one or more of the proteins, and (c) detecting the detection compound.
  • the proteins on the calcifying nano-particle can be detected by (a) binding a detection compound to one or more of the proteins, (b) capturing the calcifying nano-particle, and (c) detecting the detection compound.
  • the calcifying nano-particle can be captured by binding a capture compound to one or more of the proteins, where the capture compound is or becomes immobilized.
  • the proteins to which capture compounds bind can mediate capture, where the detection compound can be bound to one of the proteins, where the calcifying nano-particle can be characterized by determining which proteins mediate capture of the calcifying nano-particle to which the detected detection compound is bound.
  • the capture compound can be bound to one of the proteins, where the detection compounds detected can indicate which of the proteins is present on the calcifying nano-particle, where the calcifying nano-particle can be characterized by which proteins are present on the calcifying nano-particle.
  • the identified proteins can identify the type of calcifying nano-particle.
  • the identified type of calcifying nano-particle can be related to or associated with a disease or condition.
  • the identified proteins can identify a disease or condition with which calcifying nano-particles having the identified proteins are related or associated.
  • the identified proteins can identify a disease or condition that is caused by calcifying nano- particles having the identified proteins.
  • the identified proteins can identify a disease or condition in which calcifying nano-particles having the identified proteins are produced.
  • Subjects in which pathological thrombosis can occur via apatite-mediated clotting are useful targets for the disclosed methods.
  • Such subjects can include (1) Patients with vulnerable plaque rupture exposing atheroma calcification; (2) Patients undergoing angioplasty or heart-lung machine perfusion; (3) Patients with massive bone fractures or dislocated implants releasing potentially apatite particles; (4) Patients with implants, catheters, wires or stents subject to calcium encrustation; (5) Cancer patients with soft tissue calcification; and (6) Healthy or sick people with CNPs in their blood or positive calcification scores in arteries.
  • Some forms of the disclosed methods involve detection and/or identification of calcifying nano-particles and/or proteins on calcifying nano-particles.
  • Molecules of interest including calcifying nano-particles, proteins, and/or proteins in or on a calcifying nano-particle— can be detected using any suitable technique.
  • Molecules of interest to be detected can be in any sample, any composition or any other context.
  • Detection and identification of calcifying nano-particles and proteins on calcifying nano-particles can be facilitated by including labels on the disclosed compounds. Useful labels and their use are described elsewhere herein.
  • Detection of compounds bound to calcifying nano-particles and/or proteins on calcifying nano-particles indicates the presence of the bound calcifying nano-particles and/or proteins on calcifying nano-particles.
  • the disclosed compounds can be detected, for example, via labels on the compounds, by direct detection of the compounds (via an intrinsic feature of the compounds, for example), or by binding a secondary compound to the primary compound and detecting the secondary compound.
  • the secondary compound can include a label.
  • Molecules that interact with or bind to the disclosed calcifying nano-particles and proteins, such as antibodies to a protein can be detected using known techniques.
  • the detecting molecule (the compound that binds the protein of interest such as a detecting compound or capture compound) can include a label. Calcifying nano- particles and/or proteins can be contacted with the labeled molecules (such as detection compounds and capture compounds) under conditions effective and for a period of time sufficient to allow the formation of complexes. The complexes can then be generally washed to remove any non-specifically bound labeled molecules, and the remaining label in the complexes can then be detected. Detection of the label indicates the presence of the detecting molecule which in turn indicates the presence of the protein of interest or other analyte.
  • the labeled molecules such as detection compounds and capture compounds
  • an additional molecule or moiety is brought into contact with, or generated at the site of, the complex of the protein of interest and the detecting molecule.
  • a signal-generating molecule or moiety such as an enzyme can be attached to or associated with the detecting molecule.
  • the signal-generating molecule can then generate a detectable signal at the site of the immunocomplex.
  • an enzyme when supplied with suitable substrate, can produce a visible or detectable product at the site of the immunocomplex.
  • ELISAs use this type of indirect labeling.
  • an additional molecule (which can be referred to as a binding agent) that can bind to the protein of interest can be contacted with the protein complex.
  • the additional molecule can have a label or signal-generating molecule or moiety.
  • the additional molecule can be termed a secondary molecule or compound. If the secondary molecule is an antibody it can be termed a secondary antibody.
  • the complexes can be contacted with the labeled molecules under conditions effective and for a period of time sufficient to allow the formation of secondary complexes. The secondary complexes can then be generally washed to remove any non- specifically bound labeled secondary molecules, and the remaining label in the secondary complexes can then be detected.
  • the additional molecule can also be or include one of a pair of molecules or moieties that can bind to each other, such as the biotin/avidin pair.
  • the detecting molecule can include the other member of the pair.
  • Other modes of indirect labeling include the detection of primary complexes by a two step approach.
  • a molecule which can be referred to as a first binding agent, such as an antibody, that has binding affinity for the protein of interest can be used to form secondary complexes, as described above.
  • the secondary complexes can be contacted with another molecule (which can be referred to as a second binding agent) that has binding affinity for the first binding agent, again under conditions effective and for a period of time sufficient to allow the formation of complexes (thus forming tertiary complexes).
  • the second binding agent can be linked to a detectable label or signal-generating molecule or moiety, allowing detection of the tertiary complexes thus formed.
  • This system can provide for signal amplification. Methods for detecting and measuring signals generated by labels are known.
  • radioactive isotopes can be detected by scintillation counting or direct visualization; fluorescent molecules can be detected with fluorescent spectrophotometers; phosphorescent molecules can be detected with a spectrophotometer or directly visualized with a camera; enzymes can be detected by measurement or visualization of the product of a reaction catalyzed by the enzyme; antibodies can be detected by detecting a secondary detection label coupled to the antibody.
  • detection molecules are molecules which interact with a molecule of interest (such as a calcifying nano-particle and/or proteins) and to which one or more detection labels are coupled.
  • labels can be distinguished temporally via different fluorescent, phosphorescent, or chemiluminescent emission lifetimes. Multiplexed time-dependent detection is described in Squire et al., J. Microscopy 197(2):136-149 (2000), and WO 00/08443.
  • Quantitative measurement of the amount or intensity of a label can be used. For example, quantitation can be used to determine if a given label, and thus the labeled component, is present at a threshold level or amount.
  • a threshold level or amount is any desired level or amount of signal and can be chosen to suit the needs of the particular form of the method being performed.
  • Methods that involve the detection of a substance, such as a protein or an antibody to a specific protein include label-free assays, protein separation methods (i.e., electrophoresis), solid support capture assays, or in vivo detection.
  • Label-free assays are generally diagnostic means of determining the presence or absence of a specific protein, or an antibody to a specific protein, in a sample.
  • Protein separation methods are additionally useful for evaluating physical properties of the protein, such as size or net charge.
  • Capture assays are generally more useful for quantitatively evaluating the concentration of a specific protein, or antibody to a specific protein, in a sample.
  • in vivo detection is useful for evaluating the spatial expression patterns of the substance, i.e., where the substance can be found in a subject, tissue or cell.
  • Assay and detection techniques described herein use various terms, such as antigen, substance, molecule, analyte, etc., to refer molecules of interest that are to be bound or detected. Use of particular terms is not intended to be limiting. Unless the context clearly indicates otherwise, the assays and detection techniques described herein can be used to assay and detect calcifying nano-particles and proteins, such as proteins on calcifying nano-particles and/or proteins on or associated with the proteins on the calcifying nano-particles. As such, the calcifying nano-particles and proteins can be considered the antigen, substance, molecule, analyte, etc. that is bound and/or detected in the assay or detection technique.
  • Assay and detection techniques described herein refer, at various times, to the use of antibodies, such as antibodies that bind to or are specific for antigens, proteins, molecules, etc. Although many forms of the described assays and detection techniques are typically performed using antibodies, the assays and techniques for use in the disclosed methods is not intended to be limiting. Unless the context clearly indicates otherwise, the assays and detection techniques described herein that are described as using (or that commonly used) antibodies can be used with any suitable compound that can bind to the disclosed calcifying nano-particles and proteins. 1. SAPIA
  • SAPIA Surface Antigen Pattern Immunoassay
  • Said components can include, but are not limited to, proteins, peptides, isopeptide bonds, carbohydrates, lipids (fatty acids, phospholipids), endotoxin, heparin sulfate, calcium phosphate, and or nucleic acids (nucleic acid binding proteins associated with HA, amyloid protein P, etc. as associated on the particles.).
  • stable particles include spores, virus, certain bateria, any colloidal size mineral, metal biological or synthetic material particles (capable of binding antigens to its surface) and calcifying nanoparticles.
  • SAPIA calcifying nano-particles and/or components on calcifying nano-particles.
  • SAPIA allows detection of the presence of multiple proteins on CNPs ( Figures 1 A-IE).
  • An example and demonstration of SAPIA is described in the Example 1.
  • capture compounds such as antibodies specific for one or more proteins on calcifying nano-particles, are immobilized on a solid support.
  • capture compounds specific for multiple proteins on calcifying nano-particles can be situated on a single solid support and/or in an array.
  • SAPIA generally involves capture of calcifying nano-particles on a solid support via binding of one or more proteins on the calcifying nano-particles to capture compounds on the solid support.
  • the captured calcifying nano-particles can then be detected and/or identified by binding a detection compound to the calcifying nano-particles and/or one or more proteins on the calcifying nano-particles and/or one or more of proteins bound to said proteins.
  • a detection compound to the calcifying nano-particles and/or one or more proteins on the calcifying nano-particles and/or one or more of proteins bound to said proteins.
  • an array of capture compounds specific for different proteins on calcifying nano-particles is used, thus capturing calcifying nano- particles at each array location where a capture compound is present that can bind a protein on the calcifying nano-particles.
  • each type of calcifying nano-particle can bind to multiple locations where multiple different capture compounds are present in the array, hi this way detection of the presence of calcifying nano-particles at a given array location can identify a protein on the calcifying nano-particle. Such detection can be accomplished with detection compounds that bind to a single type of protein on calcifying nano-particles because only the presence of calcifying nano-particles needs to be detected.
  • capture of calcifying nano-particles can be via a single type of protein on calcifying nano- particles and detection can be via multiple types of proteins on calcifying nano-particles or capture and detection can each be via multiple types of proteins on calcifying nano- particles.
  • Immunodetection methods can be used for detecting, binding, purifying, removing and quantifying various molecules including the disclosed proteins. Further, antibodies and ligands to the disclosed calcifying nano-particles and proteins can be detected. For example, the disclosed proteins can be employed to detect antibodies having reactivity therewith. This is useful, for example, to detect whether a subject has been exposed to or has developed antibodies against a protein. Standard immunological techniques are described, e.g., in Hertzenberg, et al., Weir's Handbook of Experimental Immunology, vols. 1-4 (1996); Coligan, Current Protocols in Immunology (1991); Methods in Enzymology, vols.
  • immunoassays are enzyme linked immunosorbent assays (ELISAs), radioimmunoassays (RIA), radioimmune precipitation assays (RIPA), immunobead capture assays, Western blotting, dot blotting, gel-shift assays, Flow cytometry, protein arrays, multiplexed bead arrays, magnetic capture, in vivo imaging, fluorescence resonance energy transfer (FRET), and fluorescence recovery/localization after photobleaching (FRAP/ FLAP).
  • ELISAs enzyme linked immunosorbent assays
  • RIA radioimmunoassays
  • RIPA radioimmune precipitation assays
  • immunobead capture assays Western blotting
  • dot blotting dot blotting
  • gel-shift assays Flow cytometry
  • protein arrays multiplexed bead arrays
  • magnetic capture in vivo imaging
  • FRET fluorescence resonance energy transfer
  • FRAP/ FLAP fluorescence recovery/
  • immunoassays involve contacting a sample suspected of containing a molecule of interest (such as the disclosed calcifying nano-particles and proteins) with an antibody to the molecule of interest or contacting an antibody to a molecule of interest (such as antibodies to the disclosed proteins) with a molecule that can be bound by the antibody, as the case may be, under conditions effective to allow the formation of immunocomplexes.
  • a molecule of interest such as the disclosed calcifying nano-particles and proteins
  • an antibody to a molecule of interest such as antibodies to the disclosed proteins
  • the sample-antibody composition such as a tissue section, ELISA plate, dot blot or Western blot, can then be washed to remove any non-specifically bound antibody species, allowing only those antibodies specifically bound within the primary immune complexes to be detected.
  • the sample used can be any sample that is suspected of containing a molecule of interest (or an antibody to a molecule of interest).
  • the sample can be, for example, one or more cells, tissue, or bodily fluids such as blood, urine, semen, lymphatic fluid, cerebrospinal fluid, or amniotic fluid, or other biological samples, such as tissue culture cells, buccal swabs, mouthwash, stool, tissue slices, tissue sections, homogenized tissue extract, cell membrane preparation, biopsy aspiration, archeological samples such as bone or mummified tissue, infection samples, nosocomial infection samples, production samples, drug preparation samples, biological molecule production samples, protein preparation samples, lipid preparation samples, and/or carbohydrate preparation samples, and separated or purified forms of any of the above.
  • tissue or bodily fluids
  • tissue culture cells such as blood, urine, semen, lymphatic fluid, cerebrospinal fluid, or amniotic fluid
  • other biological samples such as tissue culture cells, buccal swabs, mouthwash, stool, tissue slices, tissue sections, homogenized tissue extract, cell membrane preparation, biopsy aspiration, archeological samples such as bone or mummified tissue,
  • Immunoassays can include methods for detecting or quantifying the amount of a molecule of interest (such as the disclosed proteins or their antibodies) in a sample, which methods generally involve the detection or quantitation of any immune complexes formed during the binding process.
  • a molecule of interest such as the disclosed proteins or their antibodies
  • the detection of immunocomplex formation is well known in the art and can be achieved through the application of numerous approaches. These methods are generally based upon the detection of a label or marker, such as any radioactive, fluorescent, biological or enzymatic tags or any other known label. See, for example, U.S.
  • Immunoassays that involve the detection of a substance, such as a protein or an antibody to a specific protein, include label-free assays, protein separation methods (i.e., electrophoresis), solid support capture assays, or in vivo detection.
  • Label-free assays are generally diagnostic means of determining the presence or absence of a specific protein, or an antibody to a specific protein, in a sample.
  • Protein separation methods are additionally useful for evaluating physical properties of the protein, such as size or net charge.
  • Capture assays are generally more useful for quantitatively evaluating the concentration of a specific protein, or antibody to a specific protein, in a sample.
  • in vivo detection is useful for evaluating the spatial expression patterns of the substance, i.e., where the substance can be found in a subject, tissue or cell.
  • the molecular complexes can be visible to the naked eye, but smaller amounts may also be detected and measured due to their ability to scatter a beam of light.
  • the formation of complexes indicates that both reactants are present, and in immunoprecipitation assays a constant concentration of a reagent antibody can be used to measure specific antigen and reagent antigens can be used to detect specific antibody. If the reagent species is previously coated onto cells (as in hemagglutination assay) or very small particles (as in latex agglutination assay),
  • clumping of the coated particles is visible at much lower concentrations.
  • assays based on these elementary principles are in common use, including Ouchterlony immunodiffusion assay, rocket Immunoelectrophoresis, and immunoturbidometric and nephelometric assays.
  • the main limitations of such assays are restricted sensitivity (lower detection limits) in comparison to assays employing labels and, in some cases, the fact that very high concentrations of analyte can actually inhibit complex formation, necessitating safeguards that make the procedures more complex.
  • a variety of instruments can directly detect molecular interactions (binding, for example). Many are based on an evanescent wave on a sensor surface with immobilized ligand, which allows continuous monitoring of binding.
  • Detection of calcifying nano-particles and/or proteins can involve the separation of the calcifying nano-particles and/or proteins by electophoresis.
  • proteins are fractionated first on the basis of one physical property, and, in a second step, on the basis of another.
  • isoelectric focusing can be used for the first dimension, conveniently carried out in a tube gel, and SDS electrophoresis in a slab gel can be used for the second dimension.
  • One example of a procedure is that of O'Farrell, P.H., High Resolution Two-dimensional Electrophoresis of Proteins, J. Biol. Chem.
  • Western Blot analysis allows the determination of the molecular mass of a protein and the measurement of relative amounts of the protein present in different samples. Detection methods include chemiluminescence and chromagenic detection. Standard methods for Western Blot analysis can be found in, for example, D.M. Bollag et al., Protein Methods (2d edition 1996) and E. Harlow & D. Lane, Antibodies, a Laboratory Manual (1988), U.S. Patent 4,452,901, each herein incorporated by reference in their entirety for their teaching regarding Western Blot methods. Generally, proteins are separated by gel electrophoresis, usually SDS-PAGE.
  • the proteins are transferred to a sheet of special blotting paper, e.g., nitrocellulose, though other types of paper, or membranes, can be used.
  • the proteins retain the same pattern of separation they had on the gel.
  • the blot is incubated with a generic protein (such as milk proteins) to bind to any remaining sticky places on the nitrocellulose.
  • An antibody is then added to the solution which is able to bind to its specific protein
  • chromogem ' c substrate e.g. alkaline phosphatase or horseradish peroxidase
  • chemiluminescent substrates e.g. alkaline phosphatase or horseradish peroxidase
  • Other possibilities for probing include the use of fluorescent or radioisotope labels (e.g., fluorescein, T).
  • Probes for the detection of antibody binding can be conjugated anti-immunoglobulins, conjugated staphylococcal Protein A (binds IgG), or probes to biotinylated primary antibodies (e.g., conjugated avidin/ streptavidin).
  • the power of the technique lies in the simultaneous detection of a specific protein by means of its antigenicity, and its molecular mass: proteins are first separated by mass in the SDS-PAGE, then specifically detected in the immunoassay step.
  • protein standards (ladders) can be run simultaneously in order to approximate molecular mass of the protein of interest in a heterogeneous sample.
  • Calcifying nano-particles and proteins can be detecting when captured or bound to a solid support (e.g., tube, well, bead, or cell).
  • a solid support e.g., tube, well, bead, or cell.
  • capture assays include Radioimmunoassay (RIA), Enzyme-Linked Immunosorbent Assay (ELISA), Flow cytometry, protein array, multiplexed bead assay, and magnetic capture.
  • RIA Radioimmunoassay
  • Radioimmunoassay is a quantitative assay for detection of binding complexes using a radioactively labeled substance (radioligand), either directly or indirectly, to measure the binding of the unlabeled substance to a specific antibody or other compound that can bind to the substance.
  • RIA involves mixing a radioactive substance (because of the ease with which iodine atoms can be introduced into tyrosine residues in a protein, the radioactive isotopes 125 I or 131 I are often used) with antibody or other compound that can bind to the substance.
  • the antibody or other compound is generally linked to a solid support, such as the tube or beads.
  • Unlabeled or "cold" substance is then adding in known quantities and the amount of labeled substance displaced is measured. Initially, the radioactive substance is bound. When cold substance is added, the two compete for binding sites - and at higher concentrations of cold substance, more binds to the antibody or compound, displacing the radioactive variant. The bound substance is separated from the unbound in solution and the radioactivity of each used to plot a binding curve. The technique is both extremely sensitive, and specific. ii. ELISAs Enzyme-Linked Immunosorbent Assay (ELISA), or more generically termed EIA (Enzyme ImmunoAssay), is an immunoassay that can detect an antibody specific for a protein.
  • ELISA Enzyme-Linked Immunosorbent Assay
  • EIA Enzyme ImmunoAssay
  • a detectable label bound to either an antibody-binding or antigen-binding reagent is an enzyme. When exposed to its substrate, this enzyme reacts in such a manner as to produce a chemical moiety which can be detected, for example, by spectrophotometric, fluorometric or visual means.
  • Enzymes which can be used to detectably label reagents useful for detection include, but are not limited to, horseradish peroxidase, alkaline phosphatase, glucose oxidase, /3-galactosidase, ribonuclease, urease, catalase, malate dehydrogenase, staphylococcal nuclease, asparaginase, yeast alcohol dehydrogenase, alpha.-glycerophosphate dehydrogenase, triose phosphate isomerase, glucose-6-phosphate dehydrogenase, glucoamylase and acetylcholinesterase.
  • ELISA procedures see Voller, A. et al.. J.
  • ELISA techniques are know to those of skill in the art.
  • antibodies that can bind to proteins can be immobilized onto a selected surface exhibiting protein affinity, such as a well in a polystyrene microtiter plate. Then, a test composition suspected of containing a marker antigen can be added to the wells. After binding and washing to remove non-specifically bound immunocomplexes, the bound antigen can be detected. Detection can be achieved by the addition of a second antibody specific for the target protein, which is linked to a detectable label.
  • ELISA is a simple "sandwich ELISA.” Detection also can be achieved by the addition of a second antibody, followed by the addition of a third antibody that has binding affinity for the second antibody, with the third antibody being linked to a detectable label.
  • competition ELISA Another variation is a competition ELISA.
  • test samples compete for binding with known amounts of labeled antigens or antibodies.
  • the amount of reactive species in the sample can be determined by mixing the sample with the known labeled species before or during incubation with coated wells. The presence of reactive species in the sample acts to reduce the amount of labeled species available for binding to the well and thus reduces the ultimate signal.
  • ELISAs have certain features in common, such as coating, incubating or binding, washing to remove non-specifically bound species, and detecting the bound immunecomplexes.
  • Antigen or antibodies can be linked to a solid support, such as in the form of plate, beads, dipstick, membrane or column matrix, and the sample to be analyzed applied to the immobilized antigen or antibody.
  • a solid support such as in the form of plate, beads, dipstick, membrane or column matrix
  • any remaining available surfaces of the wells can then be "coated" with a nonspecific protein that is antigenically neutral with regard to the test antisera.
  • a nonspecific protein that is antigenically neutral with regard to the test antisera.
  • These include bovine serum albumin (BSA), casein and solutions of milk powder.
  • BSA bovine serum albumin
  • the coating allows for blocking of nonspecific adsorption sites on the immobilizing surface and thus reduces the background caused by nonspecific binding of antisera onto the surface.
  • Such coating and blocking can be used with other capture assays and with other forms of the disclosed methods involving capture and/or solid supports.
  • a secondary or tertiary detection means rather than a direct procedure can also be used.
  • the immobilizing surface is contacted with the control sample to be tested under conditions effective to allow immunecomplex (antigen/antibody) formation. Detection of the immunecomplex then requires a labeled secondary binding agent, or a secondary binding agent in conjunction with a labeled third binding agent.
  • Under conditions effective to allow immunecomplex (antigen/antibody) formation means that the conditions include diluting the antigens and antibodies with solutions such as BSA, bovine gamma globulin (BGG) and phosphate buffered saline (PBS)/Tween. These added agents can also assist in the reduction of nonspecific background.
  • solutions such as BSA, bovine gamma globulin (BGG) and phosphate buffered saline (PBS)/Tween.
  • suitable conditions also mean that the incubation is at a temperature and for a period of time sufficient to allow effective binding. Incubation steps can typically be from about 1 minute to twelve hours, at temperatures of about 20° to 30° C, or can be incubated overnight at about 0° C to about 10° C.
  • the contacted surface can be washed so as to remove non-complexed material.
  • a washing procedure can include washing with a solution such as PBS/Tween, or borate buffer. Following the formation of specific immunecomplexes between the test sample and the originally bound material, and subsequent washing, the occurrence of even minute amounts of immunecomplexes can be determined.
  • the second or third antibody can have an associated label to allow detection, as described elsewhere herein.
  • This can be an enzyme that can generate color development upon incubating with an appropriate chromogenic substrate.
  • one can contact and incubate the first or second immunecomplex with a labeled antibody for a period of time and under conditions that favor the development of further immunecomplex formation (e.g., incubation for 2 hours at room temperature in a PBS-containing solution such as PBS-Tween).
  • the amount of label can be quantified, e.g., by incubation with a chromogenic substrate such as urea and bromocresol purple or 2,2'-azido-di-(3-ethyl- benzthiazoline-6-sulfonic acid [ABTS] and H 2 O 2 , in the case of peroxidase as the enzyme label. Quantitation can then be achieved by measuring the degree of color generation, e.g., using a visible spectra spectrophotometer. iii.
  • Flow Cytometry Flow Cytometry, fluorescent activated cell sorting (FACS), fluorescence activated sorting, and flow microfluorometry provide a means of scanning individual cells or particles for the presence of a molecule of interest. Although commonly used for analysis of cells, these techniques can be used in the disclosed method to detect, analyze and identify calcifying nano-particles and/or proteins on calcifying nano-particles.
  • Flow Cytometry is the characterization of single cells or particles as they pass at high speed through a laser beam. While a hematologist can count 200 cells in less than a minute by hand (hemocytometer) on a stage microscope, a flow cytometer can discriminate cells at speeds up to 50,000 cells/second.
  • the Flow component is a fluidics system that precisely delivers the cells at the intersection of the laser beam and light gathering lens by hydrodynamic focusing (a single stream of cells is injected and confined within an outer stream at greater pressure).
  • the laser acting as a light source develops parameters of light scatter as well as exciting the fluorescent molecules used to label the cell.
  • Cells are characterized individually by their physical and/or chemical properties (Kohler, G. and Milstein, C. (1975) Continuous Cultures of Fused Cells Secreting Antibody of Predefined Specificity. Nature 256: p. 495-49) which provide analytical parameters capable of accurate quantitation of the number of molecules/cell through Quantitative Flow Cytometry (QFCM).
  • QFCM Quantitative Flow Cytometry
  • the physical (morphological) profile of a cell or particle can be observed by combining forward light scatter (FS) and orthogonal or side light scatter (SSC).
  • FS forward light scatter
  • SSC side light scatter
  • FS forward light scatter
  • SSC side light scatter
  • This measurement is an indication of the cell's or particle's unique refractive index.
  • Side scatter is the light that is reflected 90° to the laser beam (all fluorescence is emitted and therefore collected at this angle) and is an indication of density or surface granularity.
  • a short list of some of the information that can be discerned by multiparameter (multi-color) Flow Cytometry includes; Apoptosis (programmed cell death), Cell Type, DNA Content, Enzyme Activity, Intracellular Proteins, Cell Surface Antigens,
  • Cytoplasmic Granularity Surface Membrane Integrity
  • Intracellular [Ca++]-Signal Transduction DNA Synthesis-Proliferation
  • Cell Surface Receptors Intracellular Cytokines
  • Oxidative Metabolism Intracellular pH, RNA Content, and Cell Size.
  • Antibodies can provide a useful tool for the analysis and quantitation of markers of individual cells.
  • flow cytometric analyses are described in Melamed, et al., Flow Cytometry and Sorting (1990); Shapiro, Practical Flow Cytometry (1988); and Robinson, et al., Handbook of Flow Cytometry Methods (1993), each herein incorporated by reference in its entirety for their teaching regarding FACS.
  • proteins are detected with antibodies that have been conjugated to fluorescent molecules such as FITC, PE, Texas Red, APC, etc. Molecules on the cell or particle surface can be detected.
  • the width of the laser beam maximum peak fluorescence is achieved within approximately 10 nsec as the excited outer orbital electrons return to their more stable ground state and emit a photon of light at a longer wavelength (e.g., 520 nm for FITC) than that at which they were excited.
  • Photomultiplier tubes PMT's detect these faint fluorescent signals and their sole role is to change discrete packets of light called photons (hv) into electrons and amplify them by producing as much as 10 million electrons for every photon captured.
  • Fluorescence-activated cell sorting and fluorescence-activated sorting are types of flow cytometry.
  • FACS is a method for sorting a suspension of biologic cells into two or more containers, one cell at a time.
  • FACS can also be performed on particles such as calcifying nano-particles (in which case it can be referred to as fluorescence-activated sorting).
  • Fluorescence-activated cell sorting is based upon specific light scattering and fluorescence characteristics of each cell or particle.
  • the cell or particle suspension is entrained in the center of a narrow, rapidly flowing stream of liquid. The flow is arranged so that there is a large separation between cells and particles relative to their diameter.
  • a vibrating mechanism causes the stream of cells and particles to break into individual droplets.
  • the system is adjusted so that there is a low probability of more than one cell or particle being in a droplet.
  • the flow passes through a fluorescence measuring station where the fluorescence character of interest of each cell or particle is measured.
  • An electrical charging ring is placed just at the point where the stream breaks into droplets.
  • a charge is placed on the ring based on the immediately prior fluorescence intensity measurement and the opposite charge is trapped on the droplet as it breaks from the stream.
  • the charged droplets then fall through an electrostatic deflection system that diverts droplets into containers based upon their charge.
  • Protein arrays are solid-phase ligand binding assay systems using immobilised proteins on surfaces which include glass, membranes, microtiter wells, mass spectrometer plates, and beads or other particles.
  • the assays are highly parallel (multiplexed) and often miniaturised (microarrays, protein chips). Their advantages include being rapid and automatable, capable of high sensitivity, economical on reagents, and giving an abundance of data for a single experiment. Bioinformatics support is important; the data handling demands sophisticated software and data comparison analysis. However, the software can be adapted from that used for DNA arrays, as can much of the hardware and detection systems.
  • Such systems and techniques of protein arrays can be used to detect calcifying nano-particles and/or proteins on calcifying nano-particles.
  • capture array in which ligand-binding reagents, which are usually antibodies but can also be alternative protein scaffolds, peptides or nucleic acid aptamers, are used to detect target molecules in mixtures such as plasma or tissue extracts.
  • ligand-binding reagents which are usually antibodies but can also be alternative protein scaffolds, peptides or nucleic acid aptamers, are used to detect target molecules in mixtures such as plasma or tissue extracts.
  • capture arrays can be used to carry out multiple immunoassays in parallel, both testing for several analytes in individual sera for example and testing many serum samples simultaneously.
  • proteomics capture arrays are used to quantitate and compare the levels of proteins in different samples in health and disease, i.e. protein expression profiling.
  • Proteins other than specific ligand binders are used in the array format for in vitro functional interaction screens such as protein-protein, protein- DNA, protein-drug, receptor-ligand, enzyme-substrate, etc. They may also be used to correlate the polymorphic changes resulting from SNPs with protein function.
  • the capture reagents themselves are selected and screened against many proteins, which can also be done in a multiplex array format against multiple protein targets. Analysis of multiple proteins on calcifying nano-particles can be performed using such techniques.
  • sources of proteins include cell-based expression systems for recombinant proteins, purification from natural sources, production in vitro by cell-free translation systems, and synthetic methods for peptides. Many of these methods can be automated for high throughput production.
  • Protein arrays have been designed as a miniaturisation of familiar immunoassay methods such as ELISA and dot blotting, often utilizing fluorescent readout, and facilitated by robotics and high throughput detection systems to enable multiple assays to be carried out in parallel.
  • Commonly used physical supports include glass slides, silicon, microwells, nitrocellulose or PVDF membranes, and magnetic and other microbeads.
  • microdrops of protein delivered onto planar surfaces are the most familiar format
  • alternative architectures include CD centrifugation devices based on developments in microfluidics [Gyros] and specialised chip designs, such as engineered microchannels in a plate [The Living ChipTM, Biotrove] and tiny 3D posts on a silicon surface [Zyomyx].
  • Particles in suspension can also be used as the basis of arrays, providing they are coded for identification; systems include color coding for microbeads [Luminex, Bio-Rad] and semiconductor nanocrystals [QDotsTM, Quantum Dots], and barcoding for beads [UltraPlexTM, Smartbeads] and multimetal microrods [NanobarcodesTM particles, Nanoplex Technologies]. Beads can also be assembled into planar arrays on semiconductor chips [LEAPS technology, Bio Array Solutions].
  • Immobilization of proteins involves both the coupling reagent and the nature of the surface being coupled to.
  • a good protein array support surface is chemically stable before and after the coupling procedures, allows good spot morphology, displays minimal nonspecific binding, does not contribute a background in detection systems, and is compatible with different detection systems.
  • the immobilization method used are reproducible, applicable to proteins of different properties (size, hydrophilic, hydrophobic), amenable to high throughput and automation, and compatible with retention of fully functional protein activity.
  • Orientation of the surface-bound protein is recognized as an important factor in presenting it to ligand or substrate in an active state; for capture arrays the most efficient binding results are obtained with orientated capture reagents, which generally require site-specific labeling of the protein.
  • Both covalent and noncovalent methods of protein immobilization are used and have various pros and cons. Passive adsorption to surfaces is methodologically simple, but allows little quantitative or orientational control; it may or may not alter the functional properties of the protein, and reproducibility and efficiency are variable.
  • Covalent coupling methods provide a stable linkage, can be applied to a range of proteins and have good reproducibility; however, orientation may be variable, chemical derivatization may alter the function of the protein and requires a stable interactive surface.
  • Biological capture methods utilizing a tag on the protein provide a stable linkage and bind the protein specifically and in reproducible orientation, but the biological reagent must first be immobilized adequately and the array may require special handling and have variable stability.
  • Substrates for covalent attachment include glass slides coated with amino- or aldehyde-containing silane reagents.
  • VersalinxTM system [Prolinx]
  • reversible covalent coupling is achieved by interaction between the protein derivatised with phenyldiboronic acid, and salicylhydroxamic acid immobilized on the support surface. This also has low background binding and low intrinsic fluorescence and allows the immobilized proteins to retain function.
  • Noncovalent binding of unmodified protein occurs within porous structures such as HydroGelTM [PerkinElmer], based on a 3- dimensional polyacrylamide gel; this substrate is reported to give a particularly low background on glass microarrays, with a high capacity and retention of protein function.
  • Widely used biological coupling methods are through biotin/streptavidin or hexahistidine/Ni interactions, having modified the protein appropriately.
  • Biotin may be conjugated to a poly-lysine backbone immobilised on a surface such as titanium dioxide [Zyomyx] or tantalum pentoxide [Zeptosens].
  • Array fabrication methods include robotic contact printing, ink-jetting, piezoelectric spotting and photolithography.
  • a number of commercial arrayers are available [e.g. Packard Biosience] as well as manual equipment [V & P Scientific].
  • Bacterial colonies can be robotically gridded onto PVDF membranes for induction of protein expression in situ.
  • Fluorescence labeling and detection methods are widely used. The same instrumentation as used for reading DNA microarrays is applicable to protein arrays.
  • capture (e.g. antibody) arrays can be probed with fluorescently labeled proteins from two different cell states, in which cell lysates are directly conjugated with different fluorophores (e.g. Cy-3, Cy-5) and mixed, such that the color acts as a readout for changes in target abundance.
  • Fluorescent readout sensitivity can be amplified 10-100 fold by tyramide signal amplification (TSA) [PerkinElmer Lifesciences].
  • TSA tyramide signal amplification
  • Planar waveguide technology [Zeptosens] enables ultrasensitive fluorescence detection, with the additional advantage of no intervening washing procedures.
  • High sensitivity can also be achieved with suspension beads and particles, using phycoerythrin as label [Luminex] or the properties of semiconductor nanocrystals [Quantum Dot].
  • Luminex phycoerythrin
  • Quantum Dot the properties of semiconductor nanocrystals
  • Capture arrays form the basis of diagnostic chips and arrays for expression profiling. They employ high affinity capture reagents, such as conventional antibodies, single domains, engineered scaffolds, peptides or nucleic acid aptamers, to bind and detect specific target ligands in high throughput manner.
  • Antibody arrays have the required properties of specificity and acceptable background, and some are available commercially [BD Biosciences Clontech, BioRad, Sigma]. Antibodies for capture arrays are made either by conventional immunisation (polyclonal sera and hybridomas), or as recombinant fragments, usually expressed in E. coli, after selection from phage or ribosome display libraries [Cambridge Antibody Technology, Biolnvent, Aff ⁇ tech, Biosite]. In addition to the conventional antibodies, Fab and scFv fragments, single V-domains from camelids or engineered human equivalents [Domantis] may also be useful in arrays.
  • 'scaffold' refers to ligand-binding domains of proteins, which are engineered into multiple variants capable of binding diverse target molecules with antibody-like properties of specificity and affinity.
  • the variants can be produced in a genetic library format and selected against individual targets by phage, bacterial or ribosome display.
  • Such ligand-binding scaffolds or frameworks include 'Affibodies' based on Staph, aureus protein A [Affibody], 'Trinectins' based on fibronectins [Phylos] and 'Anticalins' based on the lipocalin structure [Pieris]. These can be used on capture arrays in a similar fashion to antibodies and may have advantages of robustness and ease of production.
  • Non-protein capture molecules notably the single-stranded nucleic acid aptamers which bind protein ligands with high specificity and affinity, are also used in arrays [SomaLogic].
  • Aptamers are selected from libraries of oligonucleotides by the SelexTM procedure and their interaction with protein can be enhanced by covalent attachment, through incorporation of brominated deoxyuridine and UV-activated crosslinking (photoaptamers). Photocrosslinking to ligand reduces the crossreactivity of aptamers due to the specific steric requirements.
  • Aptamers have the advantages of ease of production by automated oligonucleotide synthesis and the stability and robustness of DNA; on photoaptamer arrays, universal fluorescent protein stains can be used to detect binding.
  • Protein analytes binding to antibody arrays may be detected directly or via a secondary antibody in a sandwich assay. Direct labeling is used for comparison of different samples with different colors. Where pairs of antibodies directed at the same protein ligand are available, sandwich immunoassays provide high specificity and sensitivity and are therefore the method of choice for low abundance proteins such as cytokines; they also give the possibility of detection of protein modifications. Label- free detection methods, including mass spectrometry, surface plasmon resonance and atomic force microscopy, avoid alteration of ligand.
  • An alternative to an array of capture molecules is one made through 'molecular imprinting' technology, in which peptides (e.g.
  • ProteinChip® array [Ciphergen]
  • Solid phase chromatographic surfaces bind proteins with similar characteristics of charge or hydrophobicity from mixtures such as plasma or tumour extracts
  • SELDI-TOF mass spectrometry is used to detection the retained proteins.
  • This technology differs from the protein arrays under discussion here since, in general, it does not involve immobilization of individual proteins for detection of specific ligand interactions.
  • protein arrays can be in vitro alternatives to the cell-based yeast two-hybrid system and may be useful where the latter is deficient, such as interactions involving secreted proteins or proteins with disulphide bridges.
  • a multiplexed bead assay such as for example the BDTM Cytometric Bead Array, is a series of spectrally discrete particles that can be used to capture and quantitate soluble analytes. The analyte is then measured by detection of a fluorescence-based emission and flow cytometric analysis. Multiplexed bead assay generates data that is comparable to ELISA based assays, but in a "multiplexed" or simultaneous fashion. Concentration of unknowns is calculated for the cytometric bead array as with any sandwich format assay, i.e. through the use of known standards and plotting unknowns against a standard curve.
  • Magnetic Capture Antibody-coated magnetic particles can be used to capture and selectively separate analytes, such as calcifying nano-particles, from solution.
  • target-specific antibody is bound to a magnetic particle (often termed an immunobead). After reaction time to allow binding of immunobead and target, a strong magnetic field is applied to selectively separate the captured target-particle complexes from the milieu. 7.
  • Imunocytochemistry and immunohistochemistry are techniques for identifying cellular or tissue constituents, respectively, by means of antigen-antibody interactions.
  • the methods generally involve administering to an animal or subject an imaging-effective amount of a detectably-labeled protein-specific antibody or fragment thereof, and then detecting the location of the labeled antibody in the sample cell or tissue.
  • An "imaging effective amount” is an amount of a detectably-labeled antibody, or fragment thereof, that when administered is sufficient to enable later detection of binding of the antibody or fragment in the specific cell or tissue.
  • the effective amount of the antibody-marker conjugate is allowed sufficient time to come into contact with reactive antigens that are present within the tissues of the subject, and the subject is then exposed to a detection device to identify the detectable marker.
  • Antibody conjugates or constructs for imaging thus have the ability to provide an image of the tissue, for example, through fluorescence microscopy, laser scanning confocal microscopy (LSCM), magnetic resonance imaging (MRT), SEM, TEM, x-ray imaging, computerized emission tomography and the like.
  • Fluorescence microscopy and laser scanning confocal microscopy (LSCM) involve the detection of fluorochrome labels, such as those provided herein.
  • Wide-field fluorescence microscopy is a very widely used technique to obtain both topographical and dynamic information. It relies on the simultaneous illumination of the whole sample.
  • the source of light is usually a mercury lamp, giving out pure white light.
  • Optical filters are then used in order to select the wavelength of excitation light (the excitation filter).
  • Excitation light is directed to the sample via a dichroic mirror (i.e., a mirror that reflects some wavelengths but is transparent to others) and fluorescent light detected by a camera (usually a CCD camera).
  • a dichroic mirror i.e., a mirror that reflects some wavelengths but is transparent to others
  • fluorescent light detected by a camera usually a CCD camera.
  • LSCM differs from wide-field fluorescence microscopy in a number of ways.
  • the light source in LSCM is one or more laser(s). This has two consequences. Firstly, the excitation light bandwidth is determined by the source, not the excitation filter and thus is much narrower than in fluorescence microscopy (2-3 nm rather than 20 - 30 nm).
  • the laser beam has to be rapidly scanned across the area in a series of lines, much like a TV image is generated.
  • the fluorescence detected at each point is measured in a photomultiplier tube (PMT) and an image built up.
  • PMT photomultiplier tube
  • the major difference between fluorescence microscopy and LSCM, however, is the pinhole, which is a device that removes unwanted, out-of-focus fluorescence, giving an optical slice of a 3-dimensional image. This "optical slicing" allows the observer to see inside the object of interest and gives clearer images, with more fine detail observable.
  • This method of illumination also has advantages in that it is possible to illuminate selected regions of the visual field allowing complex photobleaching protocols to be carried out to investigate the rates of lateral travel of fluorophores, etc. and for the excitation of different fluorophores in different regions of the same cell.
  • images can be obtained at different depths. Each image is called a z-section, and can be used to reconstruct an image of the 3- dimensional object.
  • Multi-Photon LSCM is a variation of LSCM that involves the generation of high energy fluorescence using low energy incident light. This is achieved by delivering multiple photons of excitation light to the same point in space in a sufficiently short time that the energy effectively is summed and so acts as a higher energy single photon.
  • multiphoton LSCM is innately confocal, i.e., no pinhole is required. Excitation of the fluorophore can only occur where the two photons can interact. Given the quadratic nature of the probability of two photons interacting with the fluorophore in the necessary timescale, excitation only occurs in the focal plane of the objective lens, which provides cleaner images.
  • Elements particularly useful in MPJ include the nuclear magnetic spin-resonance isotopes 157 Gd, 55 Mn, 162 Dy, 52 Cr, and 56 Fe, with gadolinium often being preferred. Radioactive substances, such as technicium 99 " 1 or indium ⁇ , that can be detected using a gamma scintillation camera or detector, also can be used. Further examples of metallic ions suitable for use in the current methods are 123 1, 131 I, 97 Ru, 67 Cu, 67 Ga, 1251, 68 Ga, 72 As, 89 Zr, and 201 Tl. A radionuclide can be bound to an antibody either directly or indirectly by using an intermediary functional group.
  • Intermediary functional groups which are often used to bind radioisotopes which exist as metallic ions to antibody are diethylenetriaminepentaacetic acid (DTPA) and ethylene diaminetetracetic acid (EDTA).
  • DTPA diethylenetriaminepentaacetic acid
  • EDTA ethylene diaminetetracetic acid
  • Administration of the antibodies can be done as disclosed herein.
  • Nucleic acid approaches for antibody delivery also exist.
  • Antibodies and antibody fragments can also be administered to patients or subjects as a nucleic acid preparation (e.g., DNA or RNA) that encodes the antibody or antibody fragment, such that the patient's or subject's own cells take up the nucleic acid and produce and secrete the encoded antibody or antibody fragment.
  • the delivery of the nucleic acid can be by any means, as disclosed herein, for example.
  • Administration of the antibody can be local or systemic and accomplished intravenously, intra-arterially, via the spinal fluid or the like. Administration also can be intradermal or intracavitary, depending upon the body site under examination. After a sufficient time has lapsed for the labeled antibody or fragment to bind to the diseased tissue, for example 30 minutes to 48 hours, the area of the subject under investigation can then be examined by an imaging technique, such as those described herein.
  • the distribution of the bound radioactive isotope and its increase or decrease with time can be monitored and recorded. By comparing the results with data obtained from studies of clinically normal individuals, the presence and extent of the diseased tissue can be determined.
  • the exact imaging protocol will necessarily vary depending upon factors specific to the subject, and depending upon the body site under examination, method of administration, type of label used and the like. One of ordinary skill in the art will be able to determine which imaging protocol to use based on these factors.
  • Effective dosages and schedules for administering the compositions can be determined empirically, and making such determinations is within the skill in the art.
  • the dosage ranges for the administration of the compositions are those large enough to produce the desired effect in which the symptoms of the disorder are affected.
  • the dosage should not be so large as to cause adverse side effects, such as unwanted cross-reactions, anaphylactic reactions, and the like.
  • the dosage will vary with the age, condition, sex and extent of the disease in the patient, route of administration, or whether other drugs are included in the regimen, and can be determined by one of skill in the art.
  • the dosage can be adjusted by the individual physician in the event of any counterindications. Dosage can vary, and can be administered in one or more dose administrations daily, for one or several days. Guidance can be found in the literature for appropriate dosages for given classes of pharmaceutical products.
  • a typical daily dosage of the antibody used alone might range from about 1 ⁇ g/kg to up to 100 mg/kg of body weight or more per day, depending on the factors mentioned above.
  • FRET Fluorescence resonance energy transfer
  • a prerequisite for this phenomenon is the very close proximity of both chromophores.
  • a result of FRET is the decrease/loss of emission by the donor chromophore while at the same time emission by the acceptor chromophore is observed.
  • a further result of FRET is shortening of the duration of the donor excited state as detected by a reduction in the fluorescence lifetime.
  • a pair of 2 chromophores which can interact in the above described manner is called a "donor-acceptor-pair" for FRET.
  • FRET fluorophore
  • This transfer is due to dipole-dipole interactions between the emission dipole of the donor and the absorption dipole of the acceptor and depends on the separation distance, the orientation between the dipoles, and the extent of overlapping energy levels (the overlap integral).
  • the inverse sixth order dependence of FRET on separation distance produces an extremely steep decline of the FRET efficiency over a couple of nanometers.
  • the typical distance for most pairs at which 50% of the molecules engage in FRET lies in the order of magnitude of average protein diameter (4-6 nm), giving rise to detectable FRET at a maximum distance of about 10 nm.
  • FRET is a very popular method to assess (fluorescently labeled) protein-protein interactions and protein conformational changes.
  • FRET can be used to detect calcifying nano-particles and/or proteins on calcifying nano-particles.
  • FRET fluorescence emission intensity-based methods that are based on the loss of donor emission and concomitant gain of acceptor emission. These are: sensitized acceptor emission, ratio imaging, acceptor photobleaching-induced donor unquenching, and anisotropy microscopy. 2) Fluorescence decay kinetics-based methods that are based on the reduced donor photobleaching phenomenon and reduced donor fluorescence lifetime (or duration of the excited state) in the presence of FRET. These are: donor photobleaching kinetics and fluorescence lifetime imaging microscopy (FLEVl).
  • FLEVl fluorescence lifetime imaging microscopy
  • FRAP (Reits andNeefjes (2001) Nat Cell Biol,Jwi;3(6) :E145-7) is a technique that reports on diffusion of fluorescently labeled biomolecules in living cells.
  • a high-power laser beam is used to photodestruct labeled biomolecules in a defined area of the cell. Diffusion (and transport) of molecules from neighboring non- illuminated areas can then repopulate the illuminated area, leading to a time-dependent recovery of fluorescence in this area. For the recovery kinetics, the diffusional recovery can be determined.
  • FLIP fluorescence loss in photobleaching
  • the high-power laser illuminates the same area in the cell for a longer period. Diffusionally connected areas in the cell, outside of the illuminated area will loose total fluorescence intensity due to continuous delivery and photodestruction in the illuminated area.
  • FRAP and FLIP can be used to detect and follow the movements of calcifying nano- particles.
  • FLAP fluorescence localization after photobleaching
  • Disclosed is a method for detecting calcifying nano-particles comprising detecting calcifying nano-particles by detecting one or more proteins on the calcifying nano-particles.
  • Also disclosed is a method for detecting one or more proteins the method comprising detecting one or more proteins on a calcifying nano-particle.
  • Also disclosed is a method of diagnosing a disease or condition comprising identifying one or more proteins on a calcifying nano-particle from a subject, wherein the identified proteins identify a disease or condition with which calcifying nano- particles having the identified proteins are related or associated.
  • Also disclosed is a method of assessing the prognosis of a disease or condition comprising identifying one or more proteins on a calcifying nano-particle from a subject, wherein the identified proteins identify calcifying nano-particles that are related to or associated with the prognosis of the disease or condition.
  • Also disclosed is a method of identifying a subject at risk of a disease or condition comprising identifying one or more proteins on a calcifying nano-particle from a subject, wherein the identified proteins identify calcifying nano-particles that are related to or associated with a risk of developing a disease or condition.
  • the calcifying nano- particle comprises one or more of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor X/Xa, CD14, Prothrombin, Factor IX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CPvP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch-1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamm
  • composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that collects said calcium binding proteins.
  • a compositon comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that has calcium binding proteins associated thereon and proteins that bind to said calcium binding proteins .
  • a hydroxy apatite calcium phosphate mineral
  • composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that has calcium binding proteins associated thereon wherein said calcium binding proteins undergo a primary conformation change as a result of said association
  • a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that has calcium binding proteins associated thereon wherein said calcium binding proteins undergo a primary conformation change as a result of said association
  • composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating containing bound calcium binding binding proteins that may experience conformational changes and wherein secondary bound proteins thereon experience conformational changes.
  • a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating containing bound calcium binding binding proteins that may experience conformational changes and wherein secondary bound proteins thereon experience conformational changes.
  • composition comprising a calcifying nano-particle and one or more compounds bound to one or more proteins on the calcifying nano-particle.
  • a method of determining the progress of treatment of a subj ect having calcifying nano-particles comprising detecting one or more proteins on calcifying nano-particles in a sample from the subject, and repeating the detection in another sample from the subject following treatment, wherein a change in the level, amount, concentration, or a combination of calcifying nano-particles in the subject indicates the progress of the treatment of the subject.
  • compositions comprising apatite and a coating material, where, for example, the coating material limits exposure of the blood of a subject when the composition is in a subject.
  • Also disclosed herein is a method of testing biocompatibility comprising testing blood coagulation in the absence of anticoagulants and a method of testing materials that will be exposed to circulating blood for formation of calcific biofilm formation.
  • the calcifying nano-particles can be detected by detecting one or more of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor X/Xa, CD 14, Prothrombin, Factor IX, Fetuin B, CD40,
  • the calcifying nano-particles can be detected by detecting two or more proteins on the calcifying nano-particles.
  • the calcifying nano-particles can be detected by detecting one or more proteins with a GLA-containing domain.
  • the calcifying nano-particles can be detected by detecting one or more proteins with a calcium binding domain.
  • the calcifying nano-particles can be captured, identified, or both prior to, simultaneous with, or following detection of one or more of the proteins. Capture or identification of the calcifying nano-particle can indicate that the detected proteins are on the calcifying nano- particles.
  • the calcifying nano-particles can be captured by binding at least one compound to one or more of the proteins, wherein the compound is or becomes immobilized.
  • the calcifying nano-particles can be identified by binding at least one compound to one or more of the proteins, wherein the calcifying nano-particles are separated based on the compound.
  • the calcifying nano-particles can be separated by fluorescence activated sorting.
  • One or more of the proteins can be detected by binding at least one compound to the protein and detecting the bound compound. Detection of two or more bound compounds can indicate that the proteins to which the compounds are bound are on the calcifying nano-particle.
  • the two or more compounds can be detected in the same location or at the same time.
  • At least one of the compounds can be an antibody, wherein the antibody is specific for the protein.
  • the calcifying nano-particles can comprise calcium phosphate and one or more of the proteins.
  • the proteins can be detected by detecting any combination of 10 or fewer of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor X/Xa, CD14, Prothrombin, Factor IX, Fetuin B, CD40,
  • the proteins can be detected by detecting any combination of 100 or fewer of the proteins.
  • the proteins can be detected by detecting any combination of 5 or fewer of the proteins.
  • the proteins can be detected by detecting any combination of 3 or fewer of the proteins.
  • the combination of proteins can be detected in the same assay.
  • the combination of proteins can be detected simultaneously.
  • the combination of proteins can be detected on the same calcifying nano-particle.
  • the combination of proteins can be detected on or within the same device.
  • the combination of proteins detected can constitute a pattern of proteins.
  • the pattern can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination including but not limited to for example, heart or circulatory diseases such as Arteriosclerosis, Atherosclerosis, Coronary Heart Disease, Chronic Heart Failure, Valve Calcifications, Arterial Aneurysms, Calcific Aortic Stenosis, Transient Cerebral Ischemia, Stroke, Peripheral Vascular Disease, Monckeberg's Disease, Vascular Thrombosis; Dental Diseases such as Dental Plaque,
  • Gum Disease (dental pulp stones), calcification of the dentinal papilla, and Salivary Gland Stones; Chronic Infection Syndromes such as Chronic Fatigue Syndrome; Kidney and Bladder Stones, Gall Stones, Pancreas and Bowel Diseases such as Pancreatic Duct Stones, Crohn's Disease, Colitis Ulcerosa; Blood disorders; Adrenal Calcification; Liver Diseases such as Liver Cirrhosis and Liver Cysts; Testicular Microliths, Chronic
  • Adenocarcinoma Skin diseases such as Calcinosis Cutis, Skin Stones, Calciphylaxis, Psoriasis, Eczema, Lichen Ruber Planus or Lichen Simple Cysts;, Choroid Plexus Calcification, Neuronal Calcification, Calcification of the FaIx Cerebri, Calcification of the Intervertebral Cartilage or Disc, Mercranial or Cerebral Calcification, Rheumatoid Arthritis, Calcific Tenditis, Oseoarthritis, Fibromyalgia, Bone Spurs, Diffuse Interstitial Skeletal Hyperostosis, Intracranial Calcifications such as Degenerative Disease Processes and Dementia; Erythrocyte-Related Diseases involving Anemia, Intraerythrocytic Nanobacterial Infection and Splenci Calcifications; Chronic Obstructive Pulmonary Disease, Broncholiths, Bronchial Stones, Neuro
  • the proteins can be detected by detecting the presence or absence of any combination of 10 or fewer of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor X/Xa, CD14, Prothrombin, Factor IX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18,
  • the pattern of the presence or absence of the proteins can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination.
  • the pattern of the presence or absence of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles.
  • the pattern of the presence or absence of the proteins can identify the type of calcifying nano- particles detected.
  • the presence of one or more of the proteins can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination.
  • the presence of one or more of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles.
  • the presence of one or more of the proteins can identify the type of calcifying nano-particles detected.
  • the absence of one or more of the proteins indicates or identifies a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination.
  • the absence of one or more of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles.
  • the absence of one or more of the proteins can identify the type of calcifying nano-particles detected.
  • the proteins can be detected using a microarray, coded beads, coated beads, flow cytometry, ELISA, mass spectrometry, fluorescence, chemiluminescence, spectrophotometry, chromatography, electrophoresis, or a combination.
  • the proteins on the calcifying nano-particle can be detected by (a) capturing the calcifying nano-particle, (b) binding a detection compound to one or more of the proteins, and (c) detecting the detection compound.
  • the proteins on the calcifying nano-particle can be detected by (a) binding a detection compound to one or more of the proteins, (b) capturing the calcifying nano-particle, and (c) detecting the detection compound.
  • the calcifying nano-particle can be captured by binding a capture compound to one or more of the proteins, where the capture compound is or becomes immobilized.
  • the proteins to which capture compounds bind can mediate capture, where the detection compound can be bound to one of the proteins, where the calcifying nano-particle can be characterized by determining which proteins mediate capture of the calcifying nano-particle to which the detected detection compound is bound.
  • the capture compound can be bound to one of the proteins, where the detection compounds detected can indicate which of the proteins is present on the calcifying nano-particle, where the calcifying nano-particle can be characterized by which proteins are present on the calcifying nano-particle.
  • the identified proteins can identify the type of calcifying nano-particle.
  • the identified type of calcifying nano-particle can be related to or associated with a disease or condition.
  • the identified proteins can identify a disease or condition with which calcifying nano-particles having the identified proteins are related or associated.
  • the identified proteins can identify a disease or condition that is caused by calcifying nano- particles having the identified proteins.
  • the identified proteins can identify a disease or condition in which calcifying nano-particles having the identified proteins are produced.
  • Subjects in which pathological thrombosis can occur via apatite-mediated clotting are useful targets for the disclosed methods.
  • Such subjects can include (1) Patients with vulnerable plaque rupture exposing atheroma calcification; (2) Patients undergoing angioplasty or heart-lung machine perfusion; (3) Patients with massive bone fractures or dislocated implants releasing potentially apatite particles; (4) Patients with implants, catheters, wires or stents subject to calcium encrustation; (5) Cancer patients with soft tissue calcification; and (6) Healthy or sick people with CNPs in their blood or positive calcification scores in arteries.
  • Such people in the last category can be identified using the disclosed compositions and methods.
  • the composition can comprise a calcifying nano-particle and one or more compounds bound to two or more proteins on the calcifying nano-particle.
  • the compound can comprise an antibody, wherein the antibody is specific for the protein.
  • the compound can block the calcifying nano-particle.
  • Example 1 In this example evidence is presented of host molecules involving two families of calcium binding Gla-proteins, calcification-defense system and clotting Gla-proteins, simultaneously binding to apatite surfaces and calcifying nano-particles. Thus, it was discovered that both Gla-systems participate in the body's calcification-defense by spatially blocking apatite surfaces. It was also realized that this creates a novel clotting mechanism. Thrombosis (the clotting of blood within an artery or vein) is a major cause of death and serious illness. Patients with circulatory, autoimmune and renal diseases, diabetes and cancers have abnormal ongoing coagulation often leading to thrombosis.
  • a clotting test was developed to measure effects of various surfaces, including apatite and calcifying nano-particles (CNPs), on blood clotting in vitro.
  • CNPs calcifying nano-particles
  • a multiplex surface antigen pattern test was also developed to demonstrate the pattern of clotting factors and their activators on the surface of CNPs isolated from human plasma and serum. This multiplex surface antigen pattern test is an example of the disclosed method for detecting calcifying nano- particles. The significance of this novel calcium mediated clotting mechanism is far- reaching since many diseases have a thrombotic component which may cause death.
  • Clinical experience in cardiovascular medicine suggested that contact of blood with exposed calcified surface leads to thrombi (Halloran and Bekavac, Neuroimaging. 2004 Oct;14(4):385-7; Demer, Int. J.
  • CAC coronary artery calcification
  • Vitamin- K-dependent, gamma-carboxyglutamic acid (Gla)-containing domains of clotting proteins in this family are homologous and are responsible for phospholipid membrane association considered to be the substratum for clotting activation cascades (Nelsestuen, Trends Cardiovasc. Med. 9, 162 (1999)). Normal hemostasis results in platelet activation, aggregation and more thrombin generation (Dumas et al., Science 301, 222 (2003)) leading to a clot covering the damaged area. Clot growth is stopped by anticoagulation cascades activating inhibitors of clotting.
  • Ga gamma-carboxyglutamic acid
  • factor Xa and thrombin are assumed to diffuse through the developing clot, filled with their specific inhibitors, to the surface of the growing clot. Formation of a large thrombus blocking a blood vessel is difficult to explain with this hypothesis, and has been experimentally shown to be insufficient (Hathcock and Nemerson, Blood 104, 123
  • clotting factors acting as proteolytic executors of the clotting cascade are calcium-binding proteins also known to bind to apatite/calcium phosphate via their calcium binding GIa domains.
  • the classical models imply that the Gla-domains undergo calcium dependent conformation changes before or concomitant with binding to phospholipid membrane. It was discovered that calcium phosphate surfaces serve the dual function as a suitable substratum (replacing phospholipid membrane) and as activators in normal and pathological blood clotting.
  • CNPs are controversial in their content and genetic characterization, critics and proponents alike agree that CNPs have a calcium phosphate mineral surface (Kajander and Ciftcioglu, Proc. Natl. Acad. Sci. U S A. 95, 8274 (1998); Cisar et al., Proc. Natl. Acad. Sci. U S A. 97, 11511 (2000); VaIi et al, Geochim. Cosmochim. Acta 65, 63 (2001); Miller et al., Am. J. Physiol. Heart Circ. Physiol. 287, Hl 115 (2004); Ciftcioglu et al., Kidney Int. 67, 483 (2005)). 1. Materials and Methods
  • CNPs Calcifying nano-particles
  • Tissues were processed to paraffin blocks, sectioned, deparaffmized and stained with H&E and with TUNEL assay for apoptotic changes with In situ Cell Death Detection Kit, AP (Roche) according to the manufacturer's instructions. Tissues were pretreated for TUNEL staining with 20 ⁇ g/ml proteinase K (Sigma, molecular biology grade) in 10 mM Tris/HCl, pH 7.4 for 15 min at room temperature. Apoptotic changes were evaluated with light microscopy.
  • the method used detected apoptosis based on labeling of DNA strand-breaks using modified nucleotide labeling by terminal deoxynucleotidyl transferase visualized with enzymic reaction using Fast Red substrate (Roche). No changes were observed in control rats exposed to sterile PBS. The study was approved by the Ethics Committee of the University of Kuopio. iii. Thrombosis detection after i.v. injection of 99m Tc-labeled apatite or CNPs in rabbits
  • Clotting induced by apatite was detected initially by using standard whole blood clotting time tube tests, with added glass beads, incubated at +37°C water bath with or without apatite.
  • the clotting times were of the order of 2 minutes and did not allow precise evaluation of subtle changes by extraneous materials on clotting time due to need of sample preparation time, such as mixing the extraneous minerals.
  • This could not be amended by using anti-coagulated blood samples (citrate or EDTA), reconstituted with 25 to 50 mM CaCl 2 at start of the test, because such samples clotted poorly indicating irreversible interference by the anticoagulant to some important player(s) in clotting.
  • a novel test platform was developed using glass slides (Menzel-Glaser, Braunschweig, Germany) incubated at room temperature. The method allows for measuring changes in the clotting time induced by contact with foreign surfaces, i.e. plain glass or coated glass, and for studying the effects of drugs on the clotting induced by foreign surface. Glass slides were coated with synthetic apatite (Poser and Price, J. Biol. Chem. 254, 43 (1979)) and controlled by TEM and EDX analysis (Kajander and giftcioglu, Proc. Natl. Acad. Sci. USA 95, 8274 (1998)).
  • apatite colloidal suspension (10% pellet containing suspension) was pipetted to each slide, and slides were dried +37°C overnight.
  • Commercial heat-fixed CNP-coated slides were obtained from Nanobac Oy, Kuopio, Finland. Plain glass slides without further processing were used as a foreign surface.
  • Effect of Calcium EDTA, disodium EDTA, and clodronate on blood clotting time was investigated by adding 10 ⁇ l solution to a plain glass slide immediately before addition of blood. Calcium EDTA and disodium EDTA were from Fluka. Clodronate was a gift from Professor Jouko Vepsalainen (University of Kuopio).
  • Venous blood was collected with venipuncture from 19 random volunteers participating in CNP epidemiological study (Ethical Committee Approval, Kuopio University). Volunteers signed an informed consent. Blood was collected with venipuncture in siliconized glass serum tubes, EDTA plasma tubes or citrate plasma tubes (Terumo), and was tested immediately after collection for whole blood clotting time on different test platforms.
  • Proteomics on proteins bound to apatite particles Protein-free apatite particles in DMEM (Gibco) without any additives were suspended into 10% FBS-DMEM and were immediately centrifuged at 14 000 rpm, 30 rain at +4°C. The pellet was washed two times by suspending with sterile PBS followed by centrifugation at 13,200 rpm, 20 min at room temperature. Pellet was frozen prior to analysis. Proteomics analysis was provided by Protana, Montreal, Canada. The SDS- boiled samples were subjected to ID SDS-PAGE under reducing conditions. Protein bands were detected by Coomassie staining, excised and processed following standard procedures including: 1. The proteins in the gel plug were reduced with DTT.
  • the peptides produced were extracted in neutral, acidic and basic conditions. vi. Mass Spectrometry Analysis The peptide mixtures were separated by C 18 reverse phase chromatography into a
  • Thermo-Finnigan LTQ-FT ion trap/FTICR hybrid mass spectrometer coupled with a nano- spray interface.
  • the mass spectrometer was operated in data-dependent mode to obtain tandem (ms/ms) spectra of each peptide above an intensity threshold as it emerged from the chromatography column.
  • the raw data files were processed using LCQ-DTA to generate peak lists of the tandem spectra.
  • the processed data was searched with Mascot (Matrix Sciences, London UK) using the NCBI non-redundant database.
  • the Mascot results were curated by mass spectrometry scientists to correlate the results with the raw data (Table 2). vii. Nanocapture and SAPIA ELISA Methods
  • Nanocapture ELISA kit Nabac Oy
  • the test measures presence of CNPs in human serum or plasma, with a measurement range from 0 to 640 units (Pretorius et al., HIV Med. 5, 391 (2004)).
  • the capture kit uses separate step-wise capture and detection reactions involving two monoclonal antibodies targeted on different surface epitopes on the CNPs.
  • SAPIA Surface Antigen Pattern Immunoassay
  • SAPIA plates were made by coating high binding polystyrene ELISA plates (Coming, USA) with antibodies against anti-calcification proteins and GIa clotting factors and control antibodies. SAPIA was controlled by using antibodies against human serum albumin, D-Dimer, NF- ⁇ B and fibronectin as these proteins were not expected to be specifically bound on particle surface ( Figure IA). Monoclonal antibodies were diluted at a final concentration of 1 ⁇ g/ml with IX PBS, pH 7.4, 100 ⁇ l/well to ELISA plates and incubated at +4°C overnight. Polyclonal antibodies were diluted to a concentration of 10 ⁇ g/ml and plates were coated as above.
  • prothrombin Activation of prothrombin by apatite in vitro Human prothrombin >95 % pure (Calbiochem) and two samples of bovine prothrombin >98 % pure (ICN, Aurora, OH and American Diagnostica, Stamford, CT) were diluted to a concentration of 10 ⁇ g/ml, 1 ⁇ g/ml and 0.1 ⁇ g/ml in 25 niM Tris, 150 mM NaCl and 5 mM CaCl 2 , pH 7.4 (which is the substrate buffer for thrombin). 20 ⁇ l of prothrombin solution was mixed with 20 ⁇ l apatite (Poser and Price, J. Biol. Chem.
  • Serum and plasma samples from 6 healthy volunteers were used for measurement of thrombin and FXa activity in particles captured with SAPIA using plates coated with antibodies against CNPs, thrombin and Factor XJXa.
  • 50 ⁇ l of serum or plasma samples were pipetted onto plates and 50 ⁇ l of Assay Buffer (0.05 M Tris, 0.15 M NaCl, 0,05% Proclin 300, pH 7.5 with 1% mouse serum) was added. Plates were incubated 1 hour at room temperature with moderate shaking. Plates were washed 4 times, before 100 ⁇ l specific substrate was added.
  • Assay Buffer 0.05 M Tris, 0.15 M NaCl, 0,05% Proclin 300, pH 7.5 with 1% mouse serum
  • Three substrates were used for thrombin: Bx-Phe-Val-Arg- pNA HCl (Bachem), Sar-Pro-Arg-pNA (Bachem) and /33-Ala-Gly-Arg-pNA-acetate (Sigma, St. Louis, MI).
  • One substrate was used for Factor Xa, CH 3 -D-CHA-GIy- Arg- pNA-AcOH (Sigma).
  • Thrombin substrates Bx-Phe-Val-Arg-pNA HCl (0.136 mg/ml) and Sar-Pro-Arg-pNA (0.25 mg/ml) were in 25 mM Tris, 150 mM NaCl, 5 mM CaCI2, pH 7.4; and /3-Ala-Gly-Arg-pNA-acetate (1 mM) in 50 mM Tris, 100 mM NaCl, 5 mM CaCl 2 , pH 7.4.
  • Factor Xa substrate was CH 3 -D-CHA-Gly-Arg-pNA-AcOH (0.5 mM) in 50 mM Tris, 100 mM NaCl, 5 mM CaCl 2 , pH 7.4.
  • Thrombin substrates Bx-Phe-Val-Arg-pNA HCl and /3-Ala-Gly-Arg-pNA-acetate failed to give positive signals.
  • Factor Xa substrate CH 3 -D-CHA-GIy- Arg-pNA- AcOH gave weak positive results for serum samples after 18 hours incubation. Results did not correlate with the presence of CNPs. Thus, the results indicate only non-specific binding of thrombin and Factor Xa activity to ELISA plate which was present only in serum samples.
  • the CNP-bound antigens must have been in an inactive form, as is expected in blood samples of healthy people.
  • Immunohistochemical staining for antigen pattern analysis Paraffin-embedded arterial tissue blocks representing various forms of severe atherosclerotic lesions were obtained from commercial sources (Clinomics BioSciences, Inc., Pittsfield MA 01201. Tissue samples were collected from New York area and processed under Institutional Review Board permit). Thin sections were cut using standard techniques. Sections were deparaffinized without decalcification and stained with monoclonal antibodies for antigen pattern analysis mapping calcification defense proteins, clotting factors and CNPs. The staining protocol was tailored for each antibody,
  • apatite formation includes several metastable calcium phosphate intermediate phases (NancoUas, Pure & Appl. Chem,l 1, 1673 (1992)).
  • BCP Basic calcium phosphate
  • Synthetic colloidal apatite was used as a control while performing acute toxicity studies for calcifying nano-particles (CNPs).
  • CNPs nano-particles
  • both iv injected apatite and CNPs caused ischemia-type tissue damage in the kidneys of rats.
  • the pathognomic feature in ischemia-reperfusion kidney damage is that glomeruli are saved whereas tubuli die (Park et al., Am. J. Physiol. Renal Physiol. 282, F352 (2002)).
  • the kidney damage was dose-dependent, and did not occur when two microliter or less apatite was injected.
  • Control animals receiving only phosphate buffered saline (PBS) did not show histological changes in kidneys. There were also signs of thrombotic events in large blood vessels and cardiac chamber walls.
  • PBS phosphate buffered saline
  • Standard blood coagulation tests e.g., activated partial thromboplastin time, prothrombin time
  • thromboplastin time e.g., activated partial thromboplastin time, prothrombin time
  • apatite surface Counteracting the anticoagulants with high calcium chloride concentrations, as is required in the tests, creates non-physiological competition for binding between free calcium (tens of times higher than the physiological) and calcium phosphate surface.
  • the apatite surface would be modified by a solution high in calcium, forming other forms of calcium minerals on the surface (e.g., octacalcium phosphate) (Boskey, J. Phys. Chem. 93, 1628 (1989)).
  • Apatite is stable under physiological calcium and phosphate concentrations. Therefore, to study the effects of apatite on clotting, a whole blood clotting slide test was developed.
  • plain objective glass, or objective glass coated with various forms of apatite, or test drugs were used as test platforms. 200 ⁇ L of freshly collected human blood was applied on the slides, which were tilted ⁇ 30°, 15 tilts per minute, at room temperature. Clotting time was established at the time when droplet contents stopped moving. The test indicated that clotting was two times faster on apatite coating compared to the control slide. CNP coating also decreased clotting time significantly (Figure 6; Table 1).
  • the method was controlled by using EDTA or citrate plasma samples, which never clotted, even when exposed to apatite coated test platforms.
  • Calcium EDTA and a small concentration of the calcium binding drug etidronate did not affect the clotting time. Therefore the test appropriately measured clotting triggered by a foreign surface, glass. It was surprising that the apatite surface was superior at inducing clotting over the untreated glass, the traditionally used foreign surface in clotting tests. ii. How does apatite cause clotting?
  • tissue factor which is a 40 kD membrane-spanning protein expressed normally by almost all cells, except the endothelium. Endothelial damage exposes tissue factor, which binds and allosterically activates a serine protease, factor Vila (FVIIa), in the presence of calcium.
  • the intrinsic pathway commences upon exposure to a foreign negatively charged surface, activating calcium-dependent conformational changes of clotting factors resulting in binding to a platelet or other phospholipid membrane, and leading to an activation-amplification cascade which eventually activates FX resulting in thrombin release.
  • Proteomics analysis revealed prothrombinase complex on apatite surface together with players of complement, antibodies and protease inhibitors. Although the use of serum to test clotting factors is not preferred, this proved the ability of apatite surface to bind clotting factors and provided information about what proteins can bind in biological situations, for instance on CNPs.
  • SAPIA profiles of CNPs using plasma and serum samples were practically identical ( Figure 3). These results indicated that serum samples can be used for the test. The results also indicated that particles with this specific antigen surface pattern can be isolated from human blood without any culturing steps. SAPIA results were stable after freeze-thawing, detergent (Tween20), EDTA or citrate application. Evidence was found that the detected proteins are cross- linked (very little protein released by SDS boiling). The stability of CNPs makes them amenable to surface antigen mapping with SAPIA technique which involves extended step-wise incubations separated by numerous washings before the detection. This feature of CNPs also allows the use of harsh treatments, when useful or desired, in other assays and detection methods.
  • SAPIA indicated that clotting factors V, VII, IX, X, tissue factor-FVIIa complex, fibrin, fibrinogen, FXIIIa, fragments of factor II, thrombin and prothrombin Fragment 1, but not prothrombin Fragment 2 are on CNPs (Tables 2 and 3; Figure 2). Both matrix
  • thrombin is retained in the particle. There may be mechanism(s) to retain it, such as crosslinking, or complex formation.
  • thrombin is known to make a complex with FXIII and fibrin (Aliens et al., Blood 100, 743 (2002)), which were also found on the particle.
  • FXIII and fibrin Aliens et al., Blood 100, 743 (2002)
  • apatite binds clotting factors and their activators, concentrating them in close proximity, thus providing the necessary players for clotting on a suitable substratum ( Figures 7-9).
  • GIa residues in the GIa domain are known to bind to apatite. Free blood calcium completes the activation by binding to the rest of Gla-residues ( Figure 8).
  • Calcium phosphate the key element in apatite, is a normal body constituent, therefore cannot be regarded as foreign surface that activates the intrinsic pathway of clotting.
  • tissue factor the key player in the extrinsic pathway
  • FVIIa FVIIa
  • the diagram depicts a novel platform, formation of complexes and activation of a clotting cascade on apatite surfaces. It was also shown that apatite itself can contribute to conformational changes leading to activation of prothrombin on apatite surfaces to release active thrombin. This non-enzymatic activation was much less rapid without the added clotting cascade players, yet proves the essential role that apatite plays. Prothrombin activation involves initial reactions with calcium, followed by a membrane prothrombinase complex formation leading to a thrombin release (Borowski et al, J. Biol. Chem. 261, 14969 (1986)).
  • apatite-mediated clotting cascade as with other clotting cascades, would have to be meticulously controlled by anti-thrombin, Protein S and C, heparin and other anti- clotting mechanisms and fibrinolytic systems to maintain a fine balance between activation and inhibition.
  • Tissue factor found on CNPs shows that apatite particles can activate clotting using extrinsic pathway players. This process could be controlled by inhibitors, for example, by tissue factor inhibitor pathway (TFIP), which is likely since CNPs were not more active than apatite, which lacked the presence of the tissue factor.
  • TFIP tissue factor inhibitor pathway
  • This example shows for two forms of apatite that sudden circulatory exposure leads to thrombotic events, indicating that exposure of blood to apatite can have catastrophic results.
  • Thrombosis was found when blood in a vessel was suddenly exposed to apatite pellet (colloidal) volume in excess of two microliters.
  • Apatite exposure of this magnitude could take place as a consequence of, for example, bone fracture, rapture of vulnerable plaque revealing pathological vascular calcification, or in any situation where circulatory apatite particle counts would become locally high, for example, after rapture of a cyst filled with them.
  • Apatite-mediated clotting can have an important physiological function in bone physiology.
  • Large bones have cancellous surface compartments with a diameter larger than largest blood vessels.
  • bone fracture often leads to clots up to 10 centimeters in diameter that must be made relatively rapidly to prevent the victim from bleeding to death.
  • Exposed apatite could serve as the platform, providing booster power for clotting, since the hollow bone cannot reduce its diameter as damaged blood vessels do via vasoconstriction, and the bone has few tissue factor sources.
  • Bone trabeculae are covered with only a monocellular layer, endostium, and the cortical bone has very low cell density (no subendothelial cells available with cell tissue factor carrying membranes as present in other tissues).
  • tissue factor-mediated clotting could take place in bone, but based on the results in this example it can be seen that the exposed bone could allow apatite-mediated clotting.
  • bone contains significant amounts of clotting GIa proteins. Those proteins are present at 1 - 2 % level of the non-collagen proteins in bone They could act with the bone Gla-protein osteocalcin, which was also found on CNPs, to control bone mineralization and/or provide protection against bleeding after bone fracture, where large areas of calcified surface are exposed. Gla-proteins are also found in kidney stones, suggesting a role in stone formation via both mineralization and thrombin production via thrombotic events or other mechanisms.
  • Prothrombin Fl is the most common protein associated with kidney stones, and thrombin has been detected in urine in kidney diseases. Thrombogenic mechanisms have been proposed for kidney stone formation (Stoller et al., J. Urol. 171, 1920 (2004)). There is a very high incidence of calcifying nano-particles in disease processes known to be associated with calcification/thrombosis, for example, 97.5% associated with carotid stenosis, whereas only 10% association in Crohn's disease.
  • CNPs are detectable just below the endothelium, they can contribute to thrombotic clotting together with the circulating CNPs when the endothelium lining is damaged.
  • the results in this example indicate a role for an apatite-mediated clotting system in thrombotic events.
  • Studies on thrombogenicity of biomaterials have examined heparin stabilized apatite, or heparinized animals. Since heparin is an anticoagulant, such studies do not reveal thrombotic potential adequately. Thus, biocompatible materials may not be hemocompatible. Apatite coated implants are widely used due to their bone biocompatibility.
  • compositions comprising apatite and a coating material, where, for example, the coating material limits exposure of the blood of a subject when the composition is in a subject.
  • results in this example may be due to the ISO 10993-4. It requires the use of citrate or hirudin blood, or plasma and allows their application on implant materials while performing hemocompatibility testing (Seyfert et al., Biomolecular Engineering 19, 91 (2002)).
  • the results in this example indicate that ISO 10993-4 required conditions cannot be used to detect blood clotting on apatite.
  • Such subject include (1) Patients with vulnerable plaque rupture exposing atheroma calcification; (2) Patients undergoing angioplasty or heart-lung machine perfusion; (3) Patients with massive bone fractures or dislocated implants releasing potentially apatite particles; (4) Patients with implants, catheters, wires or stents subject to calcium encrustation; (5) Cancer patients with soft tissue calcification; and (6) Healthy or sick people with CNPs in their blood or positive calcification scores in arteries.
  • Such people in the last category can be identified using the disclosed compositions and methods.
  • This example describes a newly discovered pathophysiological mechanism linking pathological calcification to thrombosis.
  • Blood anti-calcification Gla-proteins and GIa- clotting factor proteins were shown to bind to calcium phosphate surfaces creating a novel clotting mechanism capable of causing thrombosis where blood is in contact with apatite or CNPs. This was shown by detecting thrombosis after IV injections of apatite and CNPs in vivo in rats and rabbits, leading to thrombotic events, including ischemia- reperfusion damage.
  • a whole blood coagulation slide test was developed to measure effects of various surfaces, including apatite and CNP, on blood clotting in vitro.
  • Tables 11 and 12 illustrate the results of SAPIA testing.
  • Table 11 shows raw absorbance data in the upper half of the table for 97 proteins and components measured in 16 human serum pools. The lower half illustrates units per ml. The pools were obtained by mixing the serum from 1-5 donors for each pool, pooled according to capture ELISA results that showed similar antigen levels.
  • Table 12 shows the statistical analysis as generated from the raw data of Table 11.
  • the table shows correlation between the markers (100x100). Correlation coefficients greater than 0.5 indicate positive correlation (with low p values) and those values approaching 0.0 indicate a negative correlation. Therefore, statistical review via the generation of, for example, of box plots or scatter plots enables one skilled in the art to visualize data patterns that may be useful in the assessment, diagnosis, and therapeutic selection for certain diseases and/or conditions.
  • Various algorithmic methods may be applied, for example, by multiplying, dividing, addition, or subtraction for various antigen values. These algorithms may be used in the diagnosis of diseases and/or conditions. Data may be further analyzed via more sophisticated techniques, for instance, cluster analysis, neural network, or multivariate loigistic regression techniques.
  • Neural networks are a well-established technology for solving prediction and classification problems, using training and testing data to build a model.
  • the data involves historical data sets containing input variables, or data fields, which correspond to an output.
  • the network uses the training data to "learn" the solution to the problem by example. Since the network learns in this way, no complex models need to be created. Also, it is not necessary for your data to be complete or show a clear trend - neural networks can still converge to a solution under these conditions.
  • Logistic regression is part of a category of statistical models called generalized linear models. This broad class of models includes ordinary regression and ANOVA, as well as multivariate statistics such as ANCOVA and loglinear regression. An excellent treatment of generalized linear models is presented in Agresti (1996).
  • Logistic regression allows one to predict a discrete outcome, such as group membership, from a set of variables that maybe continuous, discrete, dichotomous, or a mix of any of these.
  • the dependent or response variable is dichotomous, such as presence/absence or success/failure.
  • Discriminant analysis is also used to predict group membership with only two groups. However, discriminant analysis can only be used with continuous independent variables. Thus, in instances where the independent variables are a categorical, or a mix of continuous and categorical, logistic regression is preferred.
  • the most important biomarkers are the presence or absence or MHC-I, Macrophage Scavenger Receptor, Osteocalcin, PGRP-I, PSA 5 Aquaporin-4.
  • the results may be better analyzed by comparison of specific marker values to the capture results.
  • the ratio of marker Macrophage 1:1.5 to (or and approximate 30 fold difference) capture whereas in prostatitis the ratio is 1:0.5.
  • the ratio result (prostate cancer) MHC-I to capture is about 5% whereas the ratio in Prostatitis is almost 1.0 or a 20 fold difference.
  • Osteocalcin shows importance as either a presence and absence value as it is not present in Cancer.
  • PSA shows a value of approximately 0.076 in Prostatitis and 0.03 in prostate cancer, or approximately 2 fold differences. This is a very small factor in favor of prostate cancer. In TG2 (labvision) the difference is .0009 in Prostatitis and approximately 0.15 in prostate cancer, a difference of approximately 166 fold.
  • Psammoma Endometrioid adenocarecenoma the most important biomarkers that are present or absent are MHC-I, Cystatin A, osteocalcin, PGRP-I Beeta, PSA, Labvisoin TG-2, Aquaporin-4.
  • Psammoma Endometrioid adenocarecenoma had 8 groups with extremely high calcification that may be, for instance, easily separated by the correlation of the presence or absence MSR and PGRP-I Beeta and Aquaporin-4. Notable is that some normal positive high value had high PSA.
  • disease specific marker tests results indicate that since the measurements were made using human blood samples different patterns of antigens on CNP may be explained only by assuming that those markers were bound on the surface of the CNP at the specific location of the pathological process. Therefore, these markers as associated with the CNP may be used to diagnose pathological processes, diseases, and ongoing processes leading to pathological problems (risk analysis and therapy follow up). This is due to the fact that different tissue and cells contain different (and the same) types of specific markers. It is well known that markers for diseases can be present YEARS before the onset of disease.
  • biomarkers can detectable prior to clinical diagnosis of disease and may be used as risk factor analysis or early detection of diseases including, but are not limited to, for example, heart or circulatory diseases such as Arteriosclerosis, Atherosclerosis, Coronary Heart Disease, Chronic Heart Failure, Valve Calcifications, Arterial Aneurysms, Calcific Aortic Stenosis, Transient Cerebral Ischemia, Stroke, Peripheral Vascular Disease, Monckeberg's Disease, Vascular Thrombosis; Dental Diseases such as Dental Plaque, Gum Disease (dental pulp stones), calcification of the dentinal papilla, and Salivary Gland Stones; Chronic Infection Syndromes such as Chronic Fatigue Syndrome; Kidney and Bladder Stones, Gall Stones, Pancreas and Bowel Diseases such as Pancreatic Duct Stones, Crohn's Disease, Colitis Ulcerosa; Blood disorders; Adrenal Calcification; Liver Diseases such as Liver Cirrhosis and Liver Cyst
  • Figure 12 shows the excretion in urine from a RAT.
  • the excretion kinetics in the urine were very different. The most pronounced differentiation was shown with the Kindey stone isolate.
  • Table 8 is a list of some proteins that can be on CNPs.
  • Table 9 is a list of proteins and compounds that can be associated with CNPs and proteins on CNPs.
  • Table 10 shows calculated unit per ml data from 8 diseases using 14 markers and 10 patient samples for each disease.
  • Table 11 shows the use of SAPIA technique to map Proteins associated with CNPS (Raw Data plus units per ml data).
  • Table 12 shows a table on correlation on SAPIA results for various proteins and antigens on CNPs (coefficients and significances).
  • Nontreat - Clodrona -38.68 -158.69 81.34
  • Nontreat - CaIEDTA -35.68 -155.69 84.34
  • Nontreat - Nanobact 133.00 33.33 232.67 ***
  • Apolipoprotein A-II (antimicrobial peptide 21 21.00 1
  • Alpha-2-antiplasmin precursor 2 13.28 1 Table 3. List of antibodies used in the SAPIA test and immunohistochemical staining (IHS).
  • Testican-3 precursor SPARC/osteonectin, CWCV, and Kazal-like domains
  • TM Thrombomodulin precursor (Fetomodulin) (CD141 antigen).
  • TM Thrombomodulin precursor (Fetomodulin) (CD141 antigen).
  • TRBM HUMAN P07204
  • Name THBD
  • Synonyms THRM ⁇ - Homo sapiens (Human)
  • Uromodulin precursor (Tamm-Horsfall urinary glycoprotein) (THP).
  • THP Tamm-Horsfall urinary glycoprotein
  • VILIP Visinin-like protein 1
  • HLP3 Hippocalcin-like protein 3
  • VISL1 HUMAN P62760
  • Name VSNL1
  • Synonyms VISL1 ⁇ - Homo sapiens (Human)
  • Nan-04-294 343.062 640.000 40.458 25.798 1.954 43.247 1.087 3.206 1.118 1.118
  • Nan-04-315 14.989 0.200 11.784 5.908 0.653 14.396 0.435 0.191 0.093 0.093
  • Nan-04-315 14.989 1.950 0.036 4.712 0.000
  • RhO O Number of Observations var8 var9 varlO varll
  • RhO O Number of Observations varl2 varl3 varl4 varl5
  • RhO O Number of Observations var24 var25 var26 var27
  • RhO O Number of Observations var32 var33 var34 var35
  • Rho 0 Number of Observations var69 var70 var71 var72

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Abstract

Disclosed are methods and compositions for detecting, analyzing and assessing the significance of calcifying nano-particles. The disclosed methods and compositions generally involve detecting one or more proteins present on a calcifying nano-particle. It has been discovered that particular proteins become associated with calcifying nano-particles. This association provides a means for detecting, classifying, analyzing, categorizing, and assessing calcifying nano-particles. Detecting particular proteins while associated with a calcifying nano-particle can be used to indicate the presence and type of calcifying nano-particle, which can be used to indicate the presence of, or disposition to, diseases or conditions. Multiple proteins on a calcifying particle can be detected. The presence or absence of particular proteins and the pattern of the presence and absence of particular proteins can be used to indicate the presence and type of calcifying nano-particle.

Description

METHODS AND COMPOSITIONS FOR THE DETECTION OF CALCIFYING
NANO-PARTICLES, IDENTIFICATION AND QUANTIFICATION OF ASSOCIATED PROTEINS THEREON, AND CORRELATION TO DISEASE
FIELD OF THE INVENTION The disclosed invention is generally in the field of calcification and calcifying bodies and specifically in the area of calcifying nano-particles. For example, the present invention discloses methods and compositions for the identication of calcifying nano- particles and protein/calcifying nanoparticles complexes and the correlation of said particles to various diseases. BACKGROUND OF THE INVENTION
Calcifying nano-particles (CNPs) are approximately 200 nm in size and appear to multiply in the biological mode, meaning their growth curve has the same characteristics as that of a life form, i.e., certain doubling time (typically around 3 days), plus a lag, a logarithmic, a stationary and even a death phase. The particles are passageable apparently indefinitely in cell culture media (Kajander and Ciftcioglu, Proc. Natl. Acad. Sci. USA 95, 8274 (1998)). The main structural component identified, without question, is bonelike apatite (Kajander and Ciftcioglu, Proc. Natl. Acad. Sci. USA 95, 8274 (1998); Miller et al., Am. J. Physiol. Heart Circ. Physiol. 287, Hl 115 (2004); Cisar et al., Proc. Natl. Acad. Sci. USA. 97, 11511 (2000); VaIi et al, Geochim. Cosmochim. Acta 65, 63 (2001); Ciftcioglu et al., Kidney Int. 67, 483 (2005)). CNPs have been isolated from kidney stones (Ciftcioglu et al., Kidney Int. 56, 1893 (1999); Khullar et al., Urol. Res. 32, 190 (2004)), gall stones (Wen et al., Chin Med. J. 118, 421 (2005)), calcific cancer (Sedivy and Battistutti, APMIS 111,951 (2003); Hudelist et al., Histopathology 45, 633 (2004)) and pathological calcifications (Miller et al., Am. J. Physiol. Heart Circ. Physiol. 287, Hl 115 (2004)). CNPs have been clearly differentiated from known biological entities: eubacteria, archaea, virus, prions and eukaryotes (Aho and Kajander, J. Clin. Microbiol. 41, 3460 (2003)).
CNPs have been shown to form mineral calcium or hydroxy apatite coatings on their surfaces. The hydroxy apatite surface acts an a mineral calcium substrate for the binding of calcium binding proteins (CaBP). Proteins that associate with the CNP
Hydroxy apatite complex (CNP/HA complex) may undergo a conformational change. Subsequently, the CNP/HA CaBP complex may attract or bind proteins that have an affinity to the aforementioned bound CaBPs. Neoeopitope formation is causal for multiple binding by host proteins. Crosslink formation is causal for multiple binding of host protein and stabilizes the structure so that it is stable and can withstand washing steps, for example, detergents, freeze thawing, etc., step involved in assays and storage functions.
Copending applications 11/102,798 , 11/180,921, and 11/182,076 disclose methods and compositions for the treatment of CNPs and are incorporated by reference hererin. Commonly assigned patents 6,706,290 (Eradication of Nanobacteria) and 5,135,851 (Culture and Detection Methods for the Sterile Filterable autonomously replicating biological particles) are incorporated by reference herein.
BRIEF SUMMARY OF THE INVENTION Disclosed are methods and compositions for detecting, analyzing and assessing the significance of calcifying nano-particles. The disclosed methods and compositions generally involve detecting one or more proteins present on a calcifying nano-particle. It has been discovered that particular proteins become associated with calcifying nano- particles. This association provides a means for detecting, classifying, analyzing, categorizing, and assessing calcifying nano-particles. Detecting particular proteins while associated with a calcifying nano-particle can be used to indicate the presence and type of calcifying nano-particle, which can be used to indicate the presence of, or disposition to, diseases or conditions. Multiple proteins on a calcifying particle can be detected. The presence or absence of particular proteins and the pattern of the presence and absence of particular proteins can be used to indicate the presence and type of calcifying nano- particle.
The disclosed method can involve detecting calcifying particles by detecting one or more proteins on the calcifying particle. The method generally can involve detecting at least one protein on the calcifying particle by binding at least one compound to the protein and detecting the bound compound. Binding a compound to the protein can involve, for example, an antibody. The antibody can be the compound and also can be the means of specific binding of the compound to the protein. As another example, a compound can be associated with an antibody with the antibody mediating binding of the compound to the protein. Detecting the bound compound can be accomplished by, for example, detecting the compound directly or indirectly. For example, the compound can be detected using, for example, a microarray, coded beads, flow cytometry, ELISA, mass spectrometry, fluorescence, chemiluminescence, spectrophotometry, chromatography, electrophoresis, or a combination. It should be understood that myriad compositions and methods are known for the detection of analytes and such can be used in and with the disclosed compositions and methods for the detection of calcifying nano-particles and proteins on calcifying nano- particles. Some such compositions and methods are described herein and others are known to those of skill in the art. It has also been discovered that particular proteins and other components are found on calcifying nano-particles and that detection of such proteins and components can serve to detect, classify, analyze, categorize, and assess calcifying nano-particles. For example, the detection of two or more particular proteins in association (in the same location or on the same particle, for example) is indicative and/or characteristic of calcifying nano- particles. As another example, the detection of a particular protein on a calcifying nano- particle is indicative and/or characteristic of calcifying nano-particles. The presence of the protein on the calcifying nano-particle and/or the identity of combinations of particular proteins serve as identifying characteristics of calcifying nano-particles.
Said proteins can undergo a conformational change as result of being associated with calcifying nano-particles. For example, calcium binding proteins will bind to the mineral calcium or hydroxy apaptite coating that surrounds calcifying nano-particles in the circulatory sytem of a mammal. There may be primary or primary and secondary changes that occur to the calcium binding protein. Secondary conformational changes involve crosslink formation between peptides or modification of amino acids in peptides by enzymes, oxidation, and chemical reactions. The conformational changes may result in neoepitopes which are specific to these conformationally changed proteins. This speficity of conformational changed proteins on the surface of the calcifying nano-particles provides for the specific discovery, detection, classification, analysis, categorization, and assessment of calcifying nano-particles as described herein is useful for diagnosing, assessing, and/or monitoring diseases associated with calcification and calcifying nano- particles, the progress of such diseases, and the progress of treatment of such diseases.
Calcifying nano-particles are implicated in and represent a risk factor for disease. For example, as described in Example 1, calcifying nano-particles can stimulate a novel blood coagulation mechanism. This mechanism can explain why thrombosis occurs in diseases associated with calcification and calcifying nano-particles. Because of this discovery, detection, classification, analysis, categorization, and assessment of calcifying nano-particles as described herein is useful for diagnosing, assessing, and/or monitoring diseases associated with calcification and calcifying nano-particles, the progress of such diseases, and the progress of treatment of such diseases.
Disclosed is a method for detecting calcifying nano-particles, where the method comprises detecting calcifying nano-particles by detecting one or more proteins on the calcifying nano-particles.
Also disclosed is a method for detecting one or more proteins, where the method comprises detecting one or more proteins on a calcifying nano-particle.
Also disclosed is a method of characterizing a calcifying nano-particle, where the method comprises identifying one or more proteins on a calcifying nano-particle. Also disclosed is a method of charactering a calcifying nano-particle, where the method comprises identifying one or more protein on a calcifying nano-partilce where said identification forms a pattern.
Also disclosed is a method using said pattern to diagnose a disease or condition.
Also disclosed is a method of diagnosing a disease or condition, where the method comprises identifying one or more proteins on a calcifying nano-particle from a subject.
The identified proteins identify a disease or condition with which calcifying nano-particles having the identified proteins are related or associated.
Also disclosed is a method of assessing the prognosis of a disease or condition, where the method comprises identifying one or more proteins on a calcifying nano-particle from a subject. The identified proteins identify calcifying nano-particles that are related to or associated with the prognosis of the disease or condition.
Also disclosed is a method of identifying a subject at risk of a disease or condition, where the method comprises identifying one or more proteins on a calcifying nano-particle from a subject. The identified proteins identify calcifying nano-particles that are related to or associated with a risk of developing a disease or condition.
Also disclosed is an isolated calcifying nano-particle, where the calcifying nano- particle comprises one or more of the proteins selected from the group consisting of proteins with a Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor XfXa, CDl 4, Prothrombin, Factor DC, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18, Larninin, Antitrypsin, Notch-1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamma-Gla residues, TF-VIIa, Complement 3c3, Complement C4, Antichymotrypsin, Annexin V, Lipid A, Isopeptide bond, Vitronectin, Thrombin, Osteocalcin, Troponin T, Vimentin, Tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, Kallikrein 6, Prothrombin Fl, Antithrombin III, Thrombin, Factor VIII, Heparan Sulphate, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c- Jun, TGase3, alpha fetoprotein, Prostate Specific Antigen, erbB2, VEGF, alpha synuclein, Mucin-1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Tgase 2, Ubiquitin, TLR 4, Cathepsin D, GFAP, RAGE, CD 9, Prostate Acid Phosphatase, Smith Antigen, PRGP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C Macrophage Scavenger Receptor Type I, Antithrombin, Protein S, BAFF on the calcifying nano-particle. Additionally, proteins that bind to calcium binding proteins may bind to said calcium binding protein/calcifying nano-particles complex including but not limited to Fetuin binding proteins, Thrombin binding proteins, Troponin binding proteins, Tropomyosin binding proteins, GLA Matric binding proteins, Fibrin binding proteins, Kallikrein binding proteins, Factor binding proteins, Matrix metalloprotinease binding proteins, Platelet glycol binding proteins, NF Kappa B binding protein, Factor X binding protein. Table 9 shows representative proteins.
Also disclosed is a composition comprising a calcifying nano-particle and one or more compounds bound to one or more proteins on the calcifying nano-particle. Also disclosed is a composition of a calcifying nano-particle comprising a hydroxy apatite (mineral calcium phosphate) coating.
Also disclosed is a composition of a calcifying nano-particle comprising said calcifying nanoparticle and a mineral calcium hydroxy apatite coating containing bound proteins that may be conformationally changed. Also disclosed is a method of determining the progress of treatment of a subj ect having calcifying nano-particles, where the method comprises detecting one or more proteins on calcifying nano-particles in a sample from the subject, and repeating the detection in another sample from the subject following treatment. A change in the level, amount, concentration, or a combination of calcifying nano-particles in the subject indicates the progress of the treatment of the subject.
Also disclosed are compositions comprising apatite and a coating material, where, for example, the coating material limits exposure of the blood of a subject when the composition is in a subject. The present applications may provide for testing of implants of other devices for the detection of CNPs, for example, stents, prosthetics, articificial valves, etc. Artificial devices are commonly covered with calcific biofilms.
Also disclosed is a method of testing biocompatibility comprising testing blood coagulation in the absence of anticoagulants. Also disclosed is a method of testing materials that will be exposed to circulating blood for formation of calcific biofilm formation.
For purposes of explanation, the term "protein" is meant to include both proteins in there natural state or proteins that have undergone a conformational change, be it primary or primary and secondary hereafter. Calcifying nano-particles can be detected by detecting one or more of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A5 Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kapρa B, Osteopontin, Factor X/Xa, CD 14, Prothrombin, Factor IX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin- 1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch- 1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamma-Gla residues, TF-VIIa, Complement 3c3, Complement C4, Antichymotrypsin, Annexin V, Lipid A, Isopeptide bond, Vitronectin, Thrombin, Osteocalcin, Troponin T, Vimentin, Tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, Kallikrein 6, Prothrombin Fl, Antithrombin III, Thrombin, Factor VIII, Heparan Sulphate, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c-Jun, TGase3, alpha fetoprotein, Prostate Specific Antigen, erbB2, VEGF, alpha synuclein, Mucin- 1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Tgase 2, Ubiquitin, TLR 4, Cathepsin D, GFAP, RAGE, CD 9, Prostate Acid Phosphatase, Smith Antigen, PRGP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C, Macrophage Scavenger Receptor Type I, Antithrombin, Protein S, BAFFon the calcifying nano-particle. Additionally, proteins that bind to calcium binding proteins may bind to said calcium binding protein/calcifying nano-particles complex including but not limited to Fetuin binding proteins, Thrombin binding proteins, Troponin binding proteins, Tropomyosin binding proteins, GLA Matric binding proteins, Fibrin binding proteins, Kallikrein binding proteins, Factor binding proteins, Matrix metalloprotinease binding proteins, Platelet glycol binding proteins, NF Kappa B binding protein, Factor X binding protein. Table 9 shows representative proteins. Calcifying nano-particles can be detected by detecting two or more proteins on the calcifying nano-particles. Calcifying nano-particles can be detected by detecting one or more proteins with a GLA-containing domain. Calcifying nano-particles can be detected by detecting one or more proteins with a calcium binding domain. Calcifying nano-particles can be captured, identified, or both prior to, simultaneous with, or following detection of one or more of the proteins. Capture or identification of the calcifying nano- particle can indicate that the detected proteins are on the calcifying nano-particles. Calcifying nano-particles can be captured by binding at least one compound to one or more of the proteins, wherein the compound is or becomes immobilized. Calcifying nano- particles can be identified by binding at least one compound to one or more of the proteins, wherein the calcifying nano-particles are separated based on the compound. Calcifying nano-particles can be separated by fluorescence activated sorting.
One or more of the proteins can be detected by binding at least one compound to the protein and detecting the bound compound. Detection of two or more bound compounds can indicate that the proteins to which the compounds are bound are on the calcifying nano-particle. The two or more compounds can be detected in the same location or at the same time. The compounds can be an antibody, where the antibody is specific for the protein. The calcifying nano-particles can comprise calcium phosphate and one or more of the proteins. The proteins can be detected by detecting any combination of 100 or fewer of the proteins selected from the group consisting of proteins with a Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor X/Xa, CD14, Prothrombin, Factor IX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch- 1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamma-Gla residues, TF-VIIa, Complement 3c3, Complement C4, Antichymotrypsin, Annexin V, Lipid A, Isopeptide bond, Vitronectin, Thrombin, Osteocalcin, Troponin T, Vimentin, Tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, Kallikrein 6, Prothrombin Fl, Antithrombin III, Thrombin, Factor VIII, Heparan Sulphate, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c-Jun, TGase3, alpha fetoprotein, Prostate Specific Antigen, erbB2, VEGF, alpha synuclein, Mucin- 1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Tgase 2, Ubiquitin, TLR 4, Cathepsin D, GFAP, RAGE, CD 9, Prostate Acid Phosphatase, Smith Antigen, PRGP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C, Macrophage Scavenger Receptor Type I, Antithrombin, Protein S, BAFF on the calcifying nano-particle. The proteins can be detected by detecting any combination of 75 or fewer of the proteins. The proteins can be detected by detecting any combination of 50 or fewer of the proteins. The proteins can be detected by detecting any combination of 25 or fewer of the proteins. The proteins can be detected by detecting any combination of 10 or fewer of the proteins. The proteins can be detected by detecting any combination of 7 or fewer of the proteins. The proteins can be detected by detecting any combination of 3 or fewer of the proteins. The combination of proteins can be detected in the same assay. The combination of proteins can be detected simultaneously. The combination of proteins can be detected on the same calcifying nano-particle. The combination of proteins can be detected on or within the same device. The combination of proteins detected can constitute a pattern of proteins. The pattern can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination. The pattern can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles. The pattern can identify the type of calcifying nano-particles detected. The proteins can be detected by detecting the presence or absence of any combination of 100 or fewer of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kaρρa B, Osteopontin, Factor XZXa, CD 14, Prothrombin, Factor IX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain,
Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch-1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer Factor V, gamma-Gla residues, TF-VIIa, Complement 3c3, Complement C4, Antichymotrypsin, Annexin V, Lipid A, Isopeptide bond, Vitronectin, Thrombin, Osteocalcin, Troponin T, Vimentin, Tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, Kallikrein 6, Prothrombin Fl, Antithrombin III, Thrombin, Factor VIII, Heparan Sulphate, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c- Jun, TGase3, alpha fetoprotein, Prostate Specific Antigen, erbB2, VEGF, alpha synuclein, Mucin- 1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Tgase 2, Ubiquitin, TLR 4, Cathepsin D, GFAP, RAGE, CD 9, Prostate Acid Phosphatase, Smith Antigen, PRGP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C, Macrophage Scavenger Receptor Type I, Antithrombin, Protein S, BAFF on the calcifying nano- particle. The pattern of the presence or absence of the proteins can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination. The pattern of the presence or absence of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles. The pattern of the presence or absence of the proteins can identify the type of calcifying nano- particles detected. The presence of one or more of the proteins can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination. The presence of one or more of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles. The presence of one or more of the proteins can identify the type of calcifying nano-particles detected. The absence of one or more of the proteins indicates or identifies a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination. The absence of one or more of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles. The absence of one or more of the proteins can identify the type of calcifying nano-particles detected. The proteins can be detected using any suitable composition, apparatus, or technique, for example, a microarray, coded beads, flow cytometry, ELISA, mass spectrometry, fluorescence, chemiluminescence, spectrophotometry, chromatography, electrophoresis, or a combination.
The proteins on the calcifying nano-particle can be detected by (a) capturing the calcifying nano-particle, (b) binding a detection compound to one or more of the proteins, and (c) detecting the detection compound. The proteins on the calcifying nano-particle can be detected by (a) binding a detection compound to one or more of the proteins, (b) capturing the calcifying nano-particle, and (c) detecting the detection compound. The calcifying nano-particle can be captured by binding a capture compound to one or more of the proteins, where the capture compound is or becomes immobilized. The proteins to which capture compounds bind can mediate capture, where the detection compound can be bound to one of the proteins, where the calcifying nano-particle can be characterized by determining which proteins mediate capture of the calcifying nano-particle to which the detected detection compound is bound. The capture compound can be bound to one of the proteins, where the detection compounds detected can indicate which of the proteins is present on the calcifying nano-particle, where the calcifying nano-particle can be characterized by which proteins are present on the calcifying nano-particle. The identified proteins can identify the type of calcifying nano-particle. The identified type of calcifying nano-particle can be related to or associated with a disease or condition. The identified proteins can identify a disease or condition with which calcifying nano-particles having the identified proteins are related or associated. The identified proteins can identify a disease or condition that is caused by calcifying nano- particles having the identified proteins. The identified proteins can identify a disease or condition in which calcifying nano-particles having the identified proteins are produced.
Subjects in which pathological thrombosis can occur via apatite-mediated clotting are useful targets for the disclosed methods. Such subjects can include (1) Patients with vulnerable plaque rupture exposing atheroma calcification; (2) Patients undergoing angioplasty or heart-lung machine perfusion; (3) Patients with massive bone fractures or dislocated implants releasing potentially apatite particles; (4) Patients with implants, catheters, wires or stents subject to calcium encrustation; (5) Cancer patients with soft tissue calcification; and (6) Healthy or sick people with CNPs in their blood or positive calcification scores in arteries. The composition can comprise a calcifying nano-particle and one or more compounds bound to two or more proteins on the calcifying nano-particle. The compound can comprise an antibody, where the antibody is specific for the protein. The compound can block the calcifying nano-particle.
Additional advantages of the disclosed method and compositions will be set forth in part in the description which follows, and in part will be understood from the description, or may be learned by practice of the disclosed method and compositions. The advantages of the disclosed method and compositions will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed. BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments of the disclosed method and compositions and together with the description, serve to explain the principles of the disclosed method and compositions.
Figures IA- IE are diagrams showing an example of Surface Antigen Pattern Immunoassay (SAPIA). CNP refers to calcifying nano-particles.
Figures 2A and 2B are graphs of levels of signal generated for various proteins in SAPIA performed on positive (Figure 2A) and negative (Figure 2B) serum and plasma samples showing same levels in serum and plasma.
Figure 3 is a scatterplot of SAPIA results for clotting matrix GLA proteins, fibrinogen and tissue factor, and CNP capture ELISA results.
Figure 4 is a graph of levels of signal generated for various proteins in SAPIA showing the presence of pro-thrombin fragments and oesteocalcin in CNPsas measured by sepia.
Figures 5 A and 5B are graphs of prothrombin activation on apatite using bovine (Figure 5A) and human (Figure 5B) prothrombin.
Figure 6 is a graph of whole blood clotting times for various materials using glass slide test. Figure 7 is a diagram of apatite-mediated clotting pathway.
Figure 8 is a diagram of a model for conformational changes caused by apatite/blood calcium binding as exemplified by prothrombin.
Figure 9 is a diagram of formation of fibrin in response to thrombotic event due to CNPs how thrombin bound to apatite surface activates formation of fibrin. Figures 1OA shows boxplots of individual disease states.
Figures 1OB shows boxplots of individual proteins correlating with disease.
Figure 1OC shows protein stip plots.
Figure 11 is a graph of clinomics samples for 15 diseases associated with CNPs. Marker values can be obtained from the disease. Figure 12 is a graph depicting urine expression showing physiological differentiations of various CNP isolates 99mTc.
Figure 13 is a graph of CNP antigen (U/niL) for Pacreatitis, Rheumatoid Arthritis and Cholecystitis. Figure 14 is a boxplot of biomarkers for negative endometrioid adenocarcinoma. Figure 15 is a boxplot for biomarkers for positive endometrioid adenocarcinoma. Figure 16 is scatterplot of markers for aortic data. Figure 17 is a scatterplot of markers for arthritis data. Figure 18 is a scatterplot of markers for cholecystitis data.
Figure 19 is a scatterplot of markers for endometrioid data. Figure 20 is a- scatterplot of markers for kidney stones data. Figure 21 is a scatterplot of markers for Parkinson's data. Figure 22 is a scatterplot of markers for prostate data. Figure 23 is a scatterplot of markers for prostatitis data.
DETAILED DESCRIPTION OF THE INVENTION The disclosed method and compositions may be understood more readily by reference to the following detailed description of particular embodiments and the Example included therein and to the Figures and their previous and following description. Disclosed are methods and compositions for detecting, analyzing and assessing the significance of calcifying nano-particles. The disclosed methods and compositions generally involve detecting one or more proteins present on a calcifying nano-particle. It has been discovered that particular proteins become associated with calcifying nano- particles. This association provides a means for detecting, classifying, analyzing, categorizing, and assessing calcifying nano-particles. Detecting particular proteins while associated with a calcifying nano-particle can be used to indicate the presence and type of calcifying nano-particle, which can be used to indicate the presence of, or disposition to, diseases or conditions. Multiple proteins on a calcifying particle can be detected. Proteins may experience a conformational change resultant from association and/or binding to the califying nano-particle. Proteins associated with calcifying nano-particles may undergo secondary conformational changes. Proteins may bind to proteins associated to calcifying nanoparticles. The presence or absence of particular proteins and the pattern of the presence and absence of particular proteins can be used to indicate the presence and type of calcifying nano-particle. The disclosed method can involve detecting calcifying particles by detecting one or more proteins on the calcifying particle. The method generally can involve detecting at least one protein on the calcifying particle by binding at least one compound to the protein and detecting the bound compound. Binding a compound to the protein can involve, for example, an antibody. The antibody can be the compound and also can be the means of specific binding of the compound to the protein. As another example, a compound can be associated with an antibody with the antibody mediating binding of the compound to the protein. Detecting the bound compound can be accomplished by, for example, detecting the compound directly or indirectly. For example, the compound can be detected using, for example, a microarray, coded beads, flow cytometry, ELISA, mass spectrometry, fluorescence, chemiluminescence, spectrophotometry, chromatography, electrophoresis, or a combination. It should be understood that myriad compositions and methods are known for the detection of analytes and such can be used in and with the disclosed compositions and methods for the detection of calcifying nano-particles and proteins on calcifying nano- particles. Some such compositions and methods are described herein and others are known to those of skill in the art.
It has been discovered that particular proteins and other components are found on calcifying nano-particles and that detection of such proteins and components can serve to detect, classify, analyze, categorize, and assess calcifying nano-particles. For example, the detection of two or more particular proteins in association (in the same location or on the same particle, for example) is indicative and/or characteristic of calcifying nano-particles. As another example, the detection of a particular protein on a calcifying nano-particle is indicative and/or characteristic of calcifying nano-particles. The presence of the protein on the calcifying nano-particle and/or the identity of combinations of particular proteins serve as identifying characteristics of calcifying nano-particles.
Detection of two or more proteins associated with calcifying nanoparticles enables the generation of a patterns that are useful for diagnosing, assessing, and/or monitoring diseases. The origin and activity of said detected proteins is usefull in the determination of a potential or active disease state in the host.
Calcifying nano-particles are implicated in and represent a risk factor for disease. For example, as described in the Example, calcifying nano-particles can stimulate a novel blood coagulation mechanism. This mechanism can explain why thrombosis occurs in diseases associated with calcification and calcifying nano-particles. Because of this discovery, detection, classification, analysis, categorization, and assessment of calcifying nano-particles as described herein is useful for diagnosing, assessing, and/or monitoring diseases associated with calcification and calcifying nano-particles, the progress of such diseases, and the progress of treatment of such diseases. It is to be understood that the disclosed method and compositions are not limited to specific synthetic methods, specific analytical techniques, or to particular reagents unless otherwise specified, and, as such, may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.
Materials
Disclosed are materials, compositions, and components that can be used for, can be used in conjunction with, can be used in preparation for, or are products of the disclosed method and compositions. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds may not be explicitly disclosed, each is specifically contemplated and described herein. For example, if a protein is disclosed and discussed and a number of modifications that can be made to a number of molecules including the protein are discussed, each and every combination and permutation of the protein and the modifications that are possible are specifically contemplated unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A-D is disclosed, then even if each is not individually recited, each is individually and collectively contemplated. Thus, in this example, each of the combinations A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are specifically contemplated and should be considered disclosed from disclosure of A, B, and C; D, E, and F; and the example combination A-D. Likewise, any subset or combination of these is also specifically contemplated and disclosed. Thus, for example, the sub-group of A-E, B-F, and C-E are specifically contemplated and should be considered disclosed from disclosure of A, B, and C; D, E, and F; and the example combination A-D. This concept applies to all aspects of this application including, but not limited to, steps in methods of making and using the disclosed compositions. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific embodiment or combination of embodiments of the disclosed methods, and that each such combination is specifically contemplated and should be considered disclosed. Disclosed is an isolated calcifying nano-particle, where the calcifying nano-particle comprises one or more of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kapρa B, Osteopontin, Factor XIXa, CDU, Prothrombin, Factor JX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin- 15 B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch-1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer Factor V, gamma-Gla residues, TF-VIIa, Complement 3c3, Complement C4, Antichymotrypsin, Annexin V, Lipid A, Isopeptide bond, Vitronectin, Thrombin,
Osteocalcin, Troponin T, Vimentin, Tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, Kallikrein 6, Prothrombin Fl, Antithrombin III, Thrombin, Factor VIII, Heparan Sulphate, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c- Jun, TGase3, alpha fetoprotein, Prostate Specific Antigen, erbB2, VEGF, alpha synuclein, Mucin-1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Tgase 2, Ubiquitin, TLR 4, Cathepsin D, GFAP, RAGE, CD 9, Prostate Acid Phosphatase, Smith Antigen, PRGP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C Macrophage Scavenger Receptor Type I, Antithrombin, Protein S, BAFF on the calcifying nano-particle. In addition, binding proteins to the aforementioned protein list can bind to the associated proteins. Proteins may or may not undergo a primary and/or secondary conformational change.
Also disclosed is a composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that collects said calcium binding proteins. Also disclosed is a compositon comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that has calcium binding proteins associated thereon and proteins that bind to said calcium binding proteins.
Also disclosed is a composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that has calcium binding proteins associated thereon wherein said calcium binding proteins undergo a primary conformation change as a result of said association Also disclosed is a composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating containing bound calcium binding binding proteins that may experience conformational changes and wherein secondary bound proteins thereon experience conformational changes.
Also disclosed is a composition comprising a calcifying nano-particle and one or more compounds bound to one or more proteins on the calcifying nano-particle.
Also disclosed are compositions comprising apatite and a coating material, where, for example, the coating material limits exposure of the blood of a subject when the composition is in a subj ect.
The composition can comprise a calcifying nano-particle and one or more compounds bound to two or more proteins on the calcifying nano-particle. The compound can comprise an antibody, where the antibody is specific for the protein. The compound can block the calcifying nano-particle. A. Compounds
The disclosed method can make use of compounds that can bind to calcifying nano-particles, such as compounds that can bind proteins on calcifying nano-particles. Detection compounds and capture compounds are examples of such compounds. Compounds for use in the disclosed methods can be any compound, molecule, material or substance that can bind to a calcifying nano-particle and/or a protein on a calcifying nano- particle. It is preferred that the compound bind specifically to the calcifying nano-particle or protein. Such specificity allows detection and identification of calcifying nano-particles and proteins. Useful compounds include antibodies and molecules that can bind to proteins on calcifying nano-particles such as ligands, substrates, proteins, cofactors, coenzymes.
Useful compounds include compounds, such as antibodies, that can bind to proteins with a Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor XJXa, CD 14, Prothrombin, Factor IX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch-1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamma-Gla residues, TF-VIIa, Complement 3c3, Complement C4, Antichymotrypsin, Annexin V, Lipid A, Isopeptide bond, Vitronectin, Thrombin, Osteocalcin, Troponin T, Vimentin, Tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, Kallikrein 6, Prothrombin Fl, Antithrombin III, Thrombin, Factor VIII, Heparan Sulphate, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c- Jun, TGase3, alpha fetoprotein, Prostate Specific Antigen, erbB2, VEGF, alpha synuclein, Mucin-1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Tgase 2, Ubiquitin, TLR 4, Cathepsin D, GFAP, RAGE, CD 9, Prostate Acid Phosphatase, Smith Antigen, PRGP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C Macrophage Scavenger Receptor Type I, Antithrombin, Protein S, BAFF. The disclosed compounds can be used for detection and capture of calcifying nano-particles and/or proteins on calcifying nano-particles. Although not limited to such uses, detecting compounds can be used for detection and capture compounds can be used for capture of calcifying nano-particles and/or proteins on calcifying nano-particles. Detection and identification of calcifying nano-particles and proteins on calcifying nano-particles can be facilitated by including labels on the disclosed compounds. Useful labels and their use are described elsewhere herein. Detection of compounds bound to calcifying nano-particles and/or proteins on calcifying nano-particles indicates the presence of the bound calcifying nano-particles and/or proteins on calcifying nano-particles. The disclosed compounds can be detected, for example, via labels on the compounds, by direct detection of the compounds (via an intrinsic feature of the compounds, for example), or by binding a secondary compound to the primary compound and detecting the secondary compound. For this purpose, the secondary compound can include a label. B. Labels
To aid in detection, identification, and/or quantitation of calcifying nano-particles and proteins on calcifying nano-particles, labels can be used. For example, labels can be incorporated into, coupled to, or associated with, compounds, detection compound, capture compound (such as compounds to be bound to proteins). A label can include, for example, a fluorescent dye, a member of binding pair, such as biotin/streptavidin, a metal (e.g., gold), or an epitope tag that can specifically interact with a molecule that can be detected, such as by producing a colored substrate or fluorescence. Many other types of labels and signals, and many other principals of signal detection and known and can also be used, some of which are described herein. For example, labels (and other compounds and components) can be detected using nuclear magnetic resonance, electron paramagnetic resonance, surface enhanced raman scattering, surface plasmon resonance, fluorescence, phosphorescence, chemiluminescence, resonance raman, microwave, photometry, mass spectrometry, or a combination.
Substances suitable for detectably labeling proteins include, for example, fluorescent dyes (also known herein as fluorochromes and fluorophores), chromophores, and enzymes that react with colorometric substrates (e.g., horseradish peroxidase). The use of fluorescent dyes is useful as they can be detected at very low amounts. Furthermore, in the case where multiple proteins are to be detected in a single assay, array, and/or system, each protein can be associated with a distinct label compound for simultaneous and/or multiplex detection. Labels can be detected using a detection device or apparatus suitable for the label to be detected, such as a fluorimeter, spectrophotomer, or mass spectrometer, the presence of a signal indicating the presence of the corresponding protein.
Fluorophores are compounds or molecules that luminesce. Typically fluorophores absorb electromagnetic energy at one wavelength and emit electromagnetic energy at a second wavelength. Representative fluorophores include, but are not limited to, 1,5 IAEDANS; 1,8-ANS; 4- Methylumbelliferone; 5-carboxy-2,7-dichlorofluorescein; 5- Carboxyfluorescein (5-FAM); 5-Carboxynapthofluorescein; 5- Carboxytetramethylrhodamine (5-TAMRA); 5 -Hydroxy Tryptamine (5-HAT); 5-ROX (carboxy-X-rhodamine); 6-Carboxyrhodamine 6G; 6-CR 6G; 6- JOE; 7-Amino-4- methylcoumarin; 7-Aminoactmomycm D (7 -AAD); 7-Hydroxy-4- 1 methylcoumariii; 9- Amino-6-chloro-2-methoxyacridine (ACMA); ABQ; Acid Fuchsin; Acridine Orange; Acridine Red; Acridine Yellow; Acriflavin; Acriflavin Feulgen SITSA; Aequorin (Photoprotein); AFPs - AutoFluorescent Protein - (Quantum Biotechnologies) see sgGFP, sgBFP; Alexa Fluor 350™; Alexa Fluor 430™; Alexa Fluor 488™; Alexa Fluor 532™; Alexa Fluor 546™; Alexa Fluor 568™; Alexa Fluor 594™; Alexa Fluor 633™; Alexa Fluor 647™; Alexa Fluor 660™; Alexa Fluor 680™; Alizarin Complexon; Alizarin Red; Allophycocyanin (APC); AMC, AMCA-S; Ammomethylcoumarin (AMCA); AMCA-X; Aminoactinomycin D; Ammocoumarin; Anilin Blue; Anthrocyl stearate; APC-Cy7; APTRA-BTC; APTS; Astrazon Brilliant Red 4G; Astrazon Orange R; Astrazon Red 6B; Astrazon Yellow 7 GLL; Atabrine; ATTO- TAG™ CBQCA; ATTO-TAG™ FQ; Auramine; Aurophosphine G; Aurophosphine; BAO 9 (Bisaminophenyloxadiazole); BCECF (high pH); BCECF (low pH); Berberine Sulphate; Beta Lactamase; BFP blue shifted GFP (Y66H); Blue Fluorescent Protein; BFP/GFP FRET; Bimane; Bisbenzemide; Bisbenzimide (Hoechst); bis- BTC; Blancophor FFG; Blancophor SV; BOBO™ -1; BOBO™-3; Bodipy492/515; Bodipy493/503; Bodipy500/510; Bodipy; 505/515; Bodipy 530/550; Bodipy 542/563; Bodipy 558/568; Bodipy 564/570; Bodipy 576/589; Bodipy 581/591 ; Bodipy 630/650-X; Bodipy 650/665-X; Bodipy 665/676; Bodipy Fl; Bodipy FL ATP; Bodipy Fl-Ceramide; Bodipy R6G SE; Bodipy TMR; Bodipy TMR-X conjugate; Bodipy TMR-X5 SE; Bodipy TR; Bodipy TR ATP; Bodipy TR-X SE; BO-PRO™ -1; BO- PRO™ -3; Brilliant Sulphoflavin FF; BTC; BTC-5N; Calcein; Calcein Blue; Calcium Crimson - ; Calcium Green; Calcium Green- 1 Ca2+ Dye; Calcium Green-2 Ca2+; Calcium Green-5N Ca2+; Calcium Green-C18 Ca2+; Calcium Orange; Calcofluor White; Carboxy- X-rhodamine (5-ROX); Cascade Blue™; Cascade Yellow; Catecholamine; CCF2 (GeneBlazer); CFDA; CFP (Cyan Fluorescent Protein); CFP/YFP FRET; Chlorophyll; Chromomycin A; Chromomycin A; CL-NERF; CMFDA; Coelenterazine; Coelenterazine cp; Coelenterazine f; Coelenterazine fcp; Coelenterazine h; Coelenterazine hep; Coelenterazine ip; Coelenterazine n; Coelenterazine O; Coumarin Phalloidin; C- phycocyanine; CPM I Methylcoumarin; CTC; CTC Formazan; Cy2™; Cy3.1 8; Cy3.5™; Cy3™; Cy5.1 8; Cy5.5™; Cy5™; Cy7™; Cyan GFP; cyclic AMP Fluorosensor (FiCRhR); Dabcyl; Dansyl; Dansyl Amine; Dansyl Cadaverine; Dansyl Chloride; Dansyl DHPE; Dansyl fluoride; DAPI; Dapoxyl; Dapoxyl 2; Dapoxyl 31DCFDA; DCFH (Dichlorodihydrofluorescein Diacetate); DDAO; DHR (Dihydorhodamine 123); Di-4- ANEPPS; Di-8-ANEPPS (non-ratio); DiA (4-Di 16-ASP); Dichlorodihydrofluorescein Diacetate (DCFH); DiD- Lipophilic Tracer; DiD (DilC18(5)); DE)S; Dihydorhodamine 123 (DHR); DiI (DiICl 8(3)); I Dinitrophenol; DiO (DiOC18(3)); DiR; DiR (DilC18(7)); DM-NERF (highpH); DNP; Dopamine; DsRed; DTAF; DY-630-NHS; DY-635-NHS; EBFP; ECFP; EGFP; ELF 97; Eosin; Erytihrosin; Erythrosin ITC; Ethidium Bromide;
Ethidium homodimer-1 (EthD-1); Euchrysin; EukoLight; Europium (111) chloride; EYFP; Fast Blue; FDA; Feulgen (Pararosaniline); FIF (Formaldehyd Induced Fluorescence); FITC; Flazo Orange; Fluo-3; Fluo-4; Fluorescein (FITC); Fluorescein Diacetate; Fluoro- Emerald; Fluoro-Gold (Hydroxystilbamidine); Fluor-Ruby; FluorX; FM 1-43™; FM 4-46; Fura Red™ (high pH); Fura Red™/Fluo-3 ; Fura-2; Fura-2/BCECF; Genacryl Brilliant Red B; Genacryl Brilliant Yellow 10GF; Genacryl Pink 3G; Genacryl Yellow 5GF; GeneBlazer; (CCF2); GFP (S65T); GFP red shifted (rsGFP); GFP wild type' non-UV excitation (wtGFP); GFP wild type, UV excitation (wtGFP); GFPuv; Gloxalic Acid; Granular blue; Haematopoφhyrin; Hoechst 33258; Hoechst 33342; Hoechst 34580; HPTS; Hydroxycoumarin; Hydroxystilbamidine (FluoroGold); Hydroxytryptamine; Indo- 1, high calcium; Indo-1 low calcium; hidodicarbocyanine (DiD); Indotricarbocyanine (DiR); Intrawhite Cf; JC-I; JO JO-I; JO-PRO-I; LaserPro; Laurodan; LDS 751 (DNA); LDS 751 (RNA); Leucophor PAF; Leucophor SF; Leucophor WS; Lissamine Rhodamine; Lissamine Rhodamine B; Calcein/Ethidium homodimer; LOLO-I; LO-PRO-I; ; Lucifer Yellow; Lyso Tracker Blue; Lyso Tracker Blue- White; Lyso Tracker Green; Lyso Tracker Red; Lyso Tracker Yellow; LysoSensor Blue; LysoSensor Green; LysoSensor Yellow/Blue; Mag Green; Magdala Red (Phloxin B); Mag-Fura Red; Mag-Fura-2; Mag- Fura-5; Mag-lndo-1 ; Magnesium Green; Magnesium Orange; Malachite Green; Marina Blue; I Maxilon Brilliant Flavin 10 GFF; Maxilon Brilliant Flavin 8 GFF; Merocyanin; Methoxycoumarin; Mitotracker Green FM; Mitotracker Orange; Mitotracker Red; Mitramycin; Monobromobimane; Monobromobimane (niBBr-GSH); Monochlorobimane; MPS (Methyl Green Pyronine Stilbene); NBD; NBD Amine; Nile Red; Nitrobenzoxedidole; Noradrenaline; Nuclear Fast Red; i Nuclear Yellow; Nylosan
Brilliant lavin E8G; Oregon Green™; Oregon Green™ 488; Oregon Green™ 500; Oregon Green™ 514; Pacific Blue; Pararosaniline (Feulgen); PBFI; PE-Cy5; PE-Cy7; PerCP; PerCP-Cy5.5; PE-TexasRed (Red 613); Phloxin B (Magdala Red); Phorwite AR; Phorwite BKL; Phorwite Rev; Phorwite RPA; Phosphine 3R; PhotoResist; Phycoerythrin B [PE]; Phycoerythrin R [PE] ; PKH26 (Sigma); PKH67; PMIA; Pontochrome Blue Black; POPO- 1; POPO-3; PO-PRO-I; PO- 1 PRO-3; Primuline; Procion Yellow; Propidium lodid (Pl); PyMPO; Pyrene; Pyronine; Pyronine B; Pyrozal Brilliant Flavin 7GF; QSY 7; Quinacrine Mustard; Resorufin; RH 414; Rhod-2; Rhodamine; Rhodamine 110; Rhodamine 123; Rhodamine 5 GLD; Rhodamine 6G; Rhodamine B; Rhodamine B 200; Rhodamine B extra; Rhodamine BB; Rhodamine BG; Rhodamine Green; Rhodamine Phallicidine; Rhodamine: Phalloidine; Rhodamine Red; Rhodamine WT; Rose Bengal; R- phycocyanine; R-phycoerythrin (PE); rsGFP; S65A; S65C; S65L; S65T; Sapphire GFP; SBFI; Serotonin; Sevron Brilliant Red 2B; Sevron Brilliant Red 4G; Sevron I Brilliant Red B; Sevron Orange; Sevron Yellow L; sgBFP™ (super glow BFP); sgGFP™ (super glow GFP); SITS (Primuline; Stilbene Isothiosulphonic Acid); SNAFL calcein; SNAFL-I ; SNAFL-2; SNARF calcein; SNARFl; Sodium Green; SpectrumAqua; SpectrumGreen; SpectrumOrange; Spectrum Red; SPQ (6-methoxy- N-(3 sulfopropyl) quinolinium); Stilbene; Sulphorhodamine B and C; Sulphorhodamine Extra; SYTO 11; SYTO 12; SYTO 13; SYTO 14; SYTO 15; SYTO 16; SYTO 17; SYTO 18; SYTO 20; SYTO 21; SYTO 22; SYTO 23; SYTO 24; SYTO 25; SYTO 40; SYTO 41; SYTO 42; SYTO 43; SYTO 44; SYTO 45; SYTO 59; SYTO 60; SYTO 61; SYTO 62; SYTO 63; SYTO 64; SYTO 80; SYTO 81; SYTO 82; SYTO 83; SYTO 84; SYTO 85; SYTOX Blue; SYTOX Green; SYTOX Orange; Tetracycline; Tetramethylrhodamine (TRITC); Texas Red™; Texas Red- X™ conjugate; Thiadicarbocyanine (DiSC3); Thiazine Red R; Thiazole Orange; Thioflavin 5; Thioflavin S; Thioflavin TON; Thiolyte; Thiozole Orange; Tinopol CBS (Calcofhior White); TIER; TO-PRO-I; TO-PRO-3; TO-PRO-5; TOTO-I; TOTO-3; Tricolor (PE-Cy5); TRITC TetramethylRodaminelsoThioCyanate; True Blue; Tru Red; Ultralite; Uranine B; Uvitex SFC; wt GFP; WW 781 ; X-Rhodamine; XRITC; Xylene Orange; Y66F; Y66H; Y66W; Yellow GFP; YFP; YO-PRO-I; YO- PRO 3; YOYO- l;Y0Y0-3; Sybr Green; Thiazole orange (interchelating dyes); semiconductor nanoparticles such as quantum dots; or caged fluorophore (which can be activated with light or other electromagnetic energy source), or a combination thereof. Other labels include molecular or metal barcodes, mass labels, and labels detectable by nuclear magnetic resonance, electron paramagnetic resonance, surface enhanced raman scattering, surface plasmon resonance, fluorescence, phosphorescence, chemiluminescence, resonance raman, microwave, photometry, mass spectrometry, or a combination. Mass labels are compounds or moieties that have, or which give the labeled component, a distinctive mass signature in mass spectroscopy. Mass labels are useful when mass spectroscopy is used for detection. Preferred mass labels are peptide nucleic acids and carbohydrates. Combinations of labels can also be useful. For example, color- encoded microbeads having, for example, 256 unique combinations of labels, are useful for distinguishing numerous components. For example, 256 different ligator-detectors can be uniquely labeled and detected allowing multiplexing and automation of the disclosed method.
Examples of useful labels are described in de Haas et al., "Platinum porphyrins as phosphorescent label for time-resolved microscopy," J. Histochem. Cytochem. 45(9):1279-92 (1997); Karger and Gesteland, "Digital chemiluminescence imaging of DNA sequencing blots using a charge-coupled device camera," Nucleic Acids Res.
20(24):6657-65 (1992); Keyes et al., "Overall and internal dynamics of DNA as monitored by five-atom-tethered spin labels," Biophys. J. 72(l):282-90 (1997); Kirschstein et al., "Detection of the DeltaF5O8 mutation in the CFTR gene by means of time- resolved fluorescence methods," Bioelectrochem. Bioenerg. 48(2):415-21 (1999); Kricka, "Selected strategies for improving sensitivity and reliability of immunoassays," Clin. Chem. 40(3):347-57 (1994); Kricka, "Chemiluminescent and bioluminescent techniques," CHn. Chem. 37(9):1472-81 (1991); Kumke et al., "Temperature and quenching studies of fluorescence polarization detection of DNA hybridization," Anal. Chem. 69(3):500-6
(1997); McCreery, "Digoxigenin labeling," MoI. Biotechnol. 7(2):121-4 (1997); Mansfield et al., "Nucleic acid detection using non-radioactive labeling methods," MoI. Cell Probes 9(3): 145-56 (1995); Nurmi et al., "A new label technology for the detection of specific polymerase chain reaction products in a closed tube," Nucleic Acids Res. 28(8):28 (2000); Oetting et al. "Multiplexed short tandem repeat polymorphisms of the Weber 8 A set of markers using tailed primers and infrared fluorescence detection," Electrophoresis 19(18):3079-83(1998); Roda et al., "Chemiluminescent imaging of enzyme-labeled probes using an optical microscope-videocamera luminograph," Anal. Biochem. 257(l):53-62 (1998); Siddiqi et al., "Evaluation of electrochemiluminescence- and bioluminescence- based assays for quantitating specific DNA," J. Clin. Lab. Anal. 10(6):423-31 (1996); Stevenson et al., "Synchronous luminescence: a new detection technique for multiple fluorescent probes used for DNA sequencing," Biotechniques 16(6): 1104-11 (1994); Vo- Dinh et al., "Surface-enhanced Raman gene probes," Anal. Chem. 66(20):3379-83 (1994); Volkers et al., "Microwave label detection technique for DNA in situ hybridization," Eur. J Morphol. 29(l):59-62 (1991).
Metal barcodes, a form of molecular barcode, can be, for example, 30-300 nm diameter by 400-4000 nm multilayer multi metal rods. These rods can be constructed by electrodeposition into an alumina mold, then the alumina is removed leaving these small multilayer objects behind. The system can have multiple zones encoded using multiple different metals where the metals have different reflectivity and thus appear lighter or darker in an optical microscope depending on the metal. For example, up to 12 zones can be encoded in up to 7 different metals. This allows practically unlimited identification codes. The metal bars can be coated with glass or other material, which can facilitate attachment of the bars to compounds to be labeled. The bars can be identified from the light dark pattern of the barcode.
Epitopes can be used as labels. Epitopes (that is, a portion of a molecule to which an antibody binds) can be composed of sugars, lipids or amino acids. Epitope tags are useful for the labeling and detection of proteins when an antibody to the protein is not available. Due to their small size, they are unlikely to affect the tagged protein's biochemical properties. Epitope tags generally range from 10 to 15 amino acids long and are designed to create a molecular handle for the protein. An epitope tag can be placed anywhere within the protein, but typically they are placed on either the amino or carboxyl terminus to minimize any potential disruption in tertiary structure and thus function of the protein. Any short stretch of amino acids known to bind an antibody could become an epitope tag. Useful epitope tags include c-myc (a 10 amino acid segment of the human protooncogene myc), haemoglutinin (HA) protein, Hisβ, Green flourescent protein (GFP), digoxigenin (DIG), and biotin. Flourescent dyes, such as those described herein, can also be used as epitope tags. C. Samples
Calcifying nano-particles and proteins on calcifying nano-particles can be any from any source, such as an animal. In general, the disclosed method is performed using a sample that contains (or is suspected of containing) calcifying nano-particles. A sample can be any sample of interest. The source, identity, and preparation of many such samples are known. The sample can be, for example, a sample from one or more cells, tissue, or bodily fluids such as blood, urine, semen, lymphatic fluid, cerebrospinal fluid, or amniotic fluid, or other biological samples, such as tissue culture cells, buccal swabs, mouthwash, stool, tissues slices, and biopsy aspiration. Types of useful samples include blood samples, urine samples, semen samples, lymphatic fluid samples, cerebrospinal fluid samples, amniotic fluid samples, biopsy samples, needle aspiration biopsy samples, cancer samples, tumor samples, tissue samples, cell samples, cell lysate samples, and/or crude cell lysate samples.
The sample can be from any organism of interest that contains or is suspected of containing calcifying nano-particles. For example, the sample can be animal, non-human animals, vertebrate, non-human vertebrate, invertebrate, insect, amphibian, avian, reptilian, fish, mammalian, non-human mammalian, rodent, farm animal, domesticated animal, bovine, porcine, murine, feline, canine, or human. The term subject can refer to any animal or any member of any subgroup or classification of animal, including those listed above and elsewhere herein. The term patient can refer to any animal under care or treatment, such as a veterinary patient or human patient. D. Solid Supports
Solid supports are solid-state substrates or supports with which molecules, such as analytes and analyte binding molecules, can be associated. Analytes, such as calcifying nano-particles and proteins, can be associated with solid supports directly or indirectly. For example, analytes can be directly immobilized on solid supports. Analyte capture agents, such a capture compounds, can also be immobilized on solid supports. A preferred form of solid support is an array. Another form of solid support is an array detector. An array detector is a solid support to which multiple different capture compounds or detection compounds have been coupled in an array, grid, or other organized pattern. Solid-state substrates for use in solid supports can include any solid material to which molecules can be coupled. This includes materials such as acrylamide, agarose, cellulose, nitrocellulose, glass, polystyrene, polyethylene vinyl acetate, polypropylene, polymethacrylate, polyethylene, polyethylene oxide, polysilicates, polycarbonates, teflon, fluorocarbons, nylon, silicon rubber, polyanhydrides, polyglycolic acid, polylactic acid, polyorthoesters, polypropylfumerate, collagen, glycosaminoglycans, and polyamino acids. Solid-state substrates can have any useful form including thin film, membrane, bottles, dishes, fibers, woven fibers, shaped polymers, particles, beads, microparticles, or a combination. Solid-state substrates and solid supports can be porous or non-porous. A preferred form for a solid-state substrate is a microtiter dish, such as a standard 96-well type. In preferred embodiments, a multiwell glass slide can be employed that normally contain one array per well. This feature allows for greater control of assay reproducibility, increased throughput and sample handling, and ease of automation.
Different compounds can be used together as a set. The set can be used as a mixture of all or subsets of the compounds used separately in separate reactions, or immobilized in an array. Compounds used separately or as mixtures can be physically separable through, for example, association with or immobilization on a solid support. An array can include a plurality of compounds immobilized at identified or predefined locations on the array. Each predefined location on the array generally can have one type of component (that is, all the components at that location are the same). Each location will have multiple copies of the component. The spatial separation of different components in the array allows separate detection and identification of calcifying nano-particles and proteins. Although preferred, it is not required that a given array be a single unit or structure. The set of compounds may be distributed over any number of solid supports. For example, at one extreme, each compound may be immobilized in a separate reaction tube or container, or on separate beads or microparticles. Different modes of the disclosed method can be performed with different components (for example, different compounds specific for different proteins) immobilized on a solid support.
Some solid supports can have capture compounds, such as antibodies, attached to a solid-state substrate. Such capture compounds can be specific for calcifying nano- particles or a protein on calcifying nano-particles. Captured calcifying nano-particles or proteins can then be detected by binding of a second, detection compound, such as an antibody. The detection compound can be specific for the same or a different protein on the calcifying nano-particle.
Methods for immobilizing antibodies (and other proteins) to solid-state substrates are well established. Immobilization can be accomplished by attachment, for example, to aminated surfaces, carboxylated surfaces or hydroxylated surfaces using standard immobilization chemistries. Examples of attachment agents are cyanogen bromide, succinimide, aldehydes, tosyl chloride, avidin-biotin, photocrosslinkable agents, epoxides and maleimides. A preferred attachment agent is the heterobifimctional cross-linker N-[γ- Maleimidobutyryloxy] succinimide ester (GMBS). These and other attachment agents, as well as methods for their use in attachment, are described in Protein immobilization: fundamentals and applications, Richard F. Taylor, ed. (M. Dekker, New York, 1991), Johnstone and Thorpe, Immunochemistry In Practice (Blackwell Scientific Publications, Oxford, England, 1987) pages 209-216 and 241-242, and Immobilized Affinity Ligands, Craig T. Hermanson et al., eds. (Academic Press, New York, 1992). Antibodies can be attached to a substrate by chemically cross-linking a free amino group on the antibody to reactive side groups present within the solid-state substrate. For example, antibodies may be chemically cross-linked to a substrate that contains free amino, carboxyl, or sulfur groups using glutaraldehyde, carbodiimides, or GMBS, respectively, as cross-linker agents. In this method, aqueous solutions containing free antibodies are incubated with the solid-state substrate in the presence of glutaraldehyde or carbodiimide.
A preferred method for attaching antibodies or other proteins to a solid-state substrate is to functionalize the substrate with an amino- or thiol-silane, and then to activate the functionalized substrate with a homobifunctional cross-linker agent such as (Bis-sulfo-succinimidyl suberate (BS3) or a heterobifunctional cross-linker agent such as GMBS. For cross-linking with GMBS, glass substrates are chemically fimctionalized by immersing in a solution of mercaptopropyltrimethoxysilane (1% vol/vol in 95% ethanol pH 5.5) for 1 hour, rinsing in 95% ethanol and heating at 120 0C for 4 hrs. Thiol- derivatized slides are activated by immersing in a 0.5 mg/ml solution of GMBS in 1% dimethylformamide, 99% ethanol for 1 hour at room temperature. Antibodies or proteins are added directly to the activated substrate, which are then blocked with solutions containing agents such as 2% bovine serum albumin, and air-dried. Other standard immobilization chemistries are known by those of skill in the art. Each of the components (compounds, for example) immobilized on the solid support preferably is located in a different predefined region of the solid support. Each of the different predefined regions can be physically separated from each other of the different regions. The distance between the different predefined regions of the solid support can be either fixed or variable. For example, in an array, each of the components can be arranged at fixed distances from each other, while components associated with beads will not be in a fixed spatial relationship. In particular, the use of multiple solid support units (for example, multiple beads) will result in variable distances.
Components can be associated or immobilized on a solid support at any density. Components preferably are immobilized to the solid support at a density exceeding 400 different components per cubic centimeter. Arrays of components can have any number of components. For example, an array can have at least 1,000 different components immobilized on the solid support, at least 10,000 different components immobilized on the solid support, at least 100,000 different components immobilized on the solid support, or at least 1,000,000 different components immobilized on the solid support. E. Kits
The materials described above as well as other materials can be packaged together in any suitable combination as a kit useful for performing, or aiding in the performance of, the disclosed method. It is useful if the kit components in a given kit are designed and adapted for use together in the disclosed method. For example disclosed are kits for detecting calcifying nano-particles, the kit comprising one or more detection compounds, one or more capture compounds, and one or more solid supports. The kits also can contain one or more buffers. F. Mixtures
Disclosed are mixtures formed by performing or preparing to perform the disclosed method. For example, disclosed are mixtures comprising a calcifying nano-particle, a detection compound, and a capture compound. Whenever the method involves mixing or bringing into contact compositions or components or reagents, performing the method creates a number of different mixtures. For example, if the method includes 3 mixing steps, after each one of these steps a unique mixture is formed if the steps are performed separately. In addition, a mixture is formed at the completion of all of the steps regardless of how the steps were performed. The present disclosure contemplates these mixtures, obtained by the performance of the disclosed methods as well as mixtures containing any disclosed reagent, composition, or component, for example, disclosed herein.
G. Systems
Disclosed are systems useful for performing, or aiding in the performance of, the disclosed method. Systems generally comprise combinations of articles of manufacture such as structures, machines, devices, and the like, and compositions, compounds, materials, and the like. Such combinations that are disclosed or that are apparent from the disclosure are contemplated. For example, disclosed and contemplated are systems comprising a calcifying nano-particle, a detection compound, and a solid support. . H. Data Structures and Computer Control
Disclosed are data structures used in, generated by, or generated from, the disclosed method. Data structures generally are any form of data, information, and/or objects collected, organized, stored, and/or embodied in a composition or medium. A pattern of proteins present on a calcifying nano-particle stored in electronic form, such as in RAM or on a storage disk, is a type of data structure.
The disclosed method, or any part thereof or preparation therefor, can be controlled, managed, or otherwise assisted by computer control. Such computer control can be accomplished by a computer controlled process or method, can use and/or generate data structures, and can use a computer program. These include such techniques as neural network that may quickly analyze and interpret data for clinical diagnosis and interpreations to indicated a disease state. Such computer control, computer controlled processes, data structures, and computer programs are contemplated and should be understood to be disclosed herein. Uses
The disclosed methods and compositions are applicable to numerous areas including, but not limited to, detecting, analyzing and assessing the significance of calcifying nano-particles. Other uses include, for example, detecting one or more proteins on a calcifying nano-particle, characterizing a calcifying nano-particle, diagnosing a disease or condition, assessing the prognosis of a disease or condition, identifying a subject at risk of a disease or condition, determining the progress of treatment of a subject having calcifying nano-particles, testing biocompatibility comprising testing blood coagulation in the absence of anticoagulants, and testing materials that will be exposed to circulating blood for formation of calcific biofilm formation. Other uses are disclosed, apparent from the disclosure, and/or will be understood by those in the art.
Method
Disclosed are methods for detecting, analyzing and assessing the significance of calcifying nano-particles. The disclosed methods generally involve detecting one or more proteins present on a calcifying nano-particle. It has been discovered that particular proteins become associated with calcifying nano-particles. This association provides a means for detecting, classifying, analyzing, categorizing, and assessing calcifying nano- particles. Detecting particular proteins while associated with a calcifying nano-particle can be used to indicate the presence and type of calcifying nano-particle, which can be used to indicate the presence of, or disposition to, diseases or conditions. Multiple proteins on a calcifying particle can be detected. The presence or absence of particular proteins and the pattern of the presence and absence of particular proteins can be used to indicate the presence and type of calcifying nano-particle.
The disclosed method can involve detecting calcifying particles by detecting one or more proteins on the calcifying particle. The method generally can involve detecting at least one protein on the calcifying particle by binding at least one compound to the protein and detecting the bound compound. Binding a compound to the protein can involve, for example, an antibody. The antibody can be the compound and also can be the means of specific binding of the compound to the protein. As another example, a compound can be associated with an antibody with the antibody mediating binding of the compound to the protein. Detecting the bound compound can be accomplished by, for example, detecting the compound directly or indirectly. For example, the compound can be detected using, for example, a microarray, coded beads, coated beads, flow cytometry, ELISA, mass spectrometry, fluorescence, chemiluminescence, spectrophotometry, chromatography, electrophoresis, or a combination.
Detection and identification of calcifying nano-particles and proteins on calcifying nano-particles can be facilitated by including labels on the disclosed compounds. Useful labels and their use are described elsewhere herein. Detection of compounds bound to calcifying nano-particles and/or proteins on calcifying nano-particles indicates the presence of the bound calcifying nano-particles and/or proteins on calcifying nano- particles. The disclosed compounds can be detected, for example, via labels on the compounds, by direct detection of the compounds (via an intrinsic feature of the compounds, for example), or by binding a secondary compound to the primary compound and detecting the secondary compound. For this purpose, the secondary compound can include a label.
Disclosed is a method for detecting calcifying nano-particles, where the method comprises detecting calcifying nano-particles by detecting one or more proteins on the calcifying nano-particles.
Also disclosed is a composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that collects said calcium binding proteins.
Also disclosed is a compositon comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that has calcium binding proteins associated thereon and proteins that bind to said calcium binding proteins.
Also disclosed is a composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that has calcium binding proteins associated thereon wherein said calcium binding proteins undergo a primary conformation change as a result of said association
Also disclosed is a composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating containing bound calcium binding binding proteins that may experience conformational changes and s secondary bound proteins thereon that experience conformational changes.
Also disclosed is a method for detecting one or more proteins, where the method comprises detecting one or more proteins on a calcifying nano-particle. Also disclosed is a method of characterizing a calcifying nano-particle, where the method comprises identifying one or more proteins on a calcifying nano-particle.
Also disclosed is a method of diagnosing a disease or condition, where the method comprises identifying one or more proteins on a calcifying nano-particle from a subject. The identified proteins identify a disease or condition with which calcifying nano-particles having the identified proteins are related or associated.
Also disclosed is a method of assessing the prognosis of a disease or condition, where the method comprises identifying one or more proteins on a calcifying nano-particle from a subject. The identified proteins identify calcifying nano-particles that are related to or associated with the prognosis of the disease or condition.
Also disclosed is a method of identifying a subject at risk of a disease or condition, where the method comprises identifying one or more proteins on a calcifying nano-particle from a subject. The identified proteins identify calcifying nano-particles that are related to or associated with a risk of developing a disease or condition. Also disclosed is a method of determining the progress of treatment of a subj ect having calcifying nano-particles, where the method comprises detecting one or more proteins on calcifying nano-particles in a sample from the subject, and repeating the detection in another sample from the subject following treatment. A change in the level, amount, concentration, or a combination of calcifying nano-particles in the subject indicates the progress of the treatment of the subj ect.
Also disclosed is a method of testing biocompatibility comprising testing blood coagulation in the absence of anticoagulants.
Also disclosed is a method of testing materials that will be exposed to circulating blood for formation of calcific biofilm formation. Calcifying nano-particles can be detected by detecting one or more of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kapρa B, Osteopontin, Factor X/Xa, CD 14, Prothrombin, Factor IX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin- 1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch- 1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamma-Gla residues, TF-VIIa, Complement 3c3, Complement C4, Antichymotrypsin, Annexin V, Lipid A, Isopeptide bond, Vitronectin, Thrombin, Osteocalcin, Troponin T, Vimentin, Tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, Kallikrein 6, Prothrombin Fl , Antithrombin III, Thrombin, Factor VIII, Heparan Sulphate, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c-Jun, TGase3, alpha fetoprotein, Prostate Specific Antigen, erbB2, VEGF, alpha synuclein, Mucin-1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Tgase 2, Ubiquitin, TLR 4, Cathepsin D, GFAP, RAGE, CD 9, Prostate Acid Phosphatase, Smith Antigen, PRGP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C, Macrophage Scavenger Receptor Type I, Antithrombin, Protein S, BAFF on the calcifying nano-particle. Additionally, proteins that bind to the aforementioned protein list may also become associated with the calcifying nanoparticles. Said proteins may or may not undergo conformational changes.
Calcifying nano-particles can be detected by detecting two or more proteins on the calcifying nano-particles. Calcifying nano-particles can be detected by detecting one or more proteins with a GLA-containing domain. Calcifying nano-particles can be detected by detecting one or more proteins with a calcium binding domain. Calcifying nano- particles can be captured, identified, or both prior to, simultaneous with, or following detection of one or more of the proteins. Capture or identification of the calcifying nano- particle can indicate that the detected proteins are on the calcifying nano-particles. Calcifying nano-particles can be captured by binding at least one compound to one or more of the proteins, wherein the compound is or becomes immobilized. Calcifying nano- particles can be identified by binding at least one compound to one or more of the proteins, wherein the calcifying nano-particles are separated based on the compound. Calcifying nano-particles can be separated by fluorescence activated sorting.
One or more of the proteins can be detected by binding at least one compound to the protein and detecting the bound compound. Detection of two or more bound compounds can indicate that the proteins to which the compounds are bound are on the calcifying nano-particle. The two or more compounds can be detected in the same location or at the same time. The compounds can be an antibody, where the antibody is specific for the protein. The calcifying nano-particles can comprise calcium phosphate and one or more of the proteins.
The proteins can be detected by detecting any combination of 10 or fewer of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappaB, Osteopontin, Factor X/Xa, CD 14, Prothrombin, Factor FX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch- 1 , BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamma-Gla residues, TF-VIIa, Complement 3c3, Complement C4, Antichymotrypsin, Annexin V, Lipid A, Isopeptide bond, Vitronectin, Thrombin, Osteocalcin, Troponin T, Vimentin, Tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, Kallikrein 6, Prothrombin Fl, Antithrombin III, Thrombin, Factor VIII, Heparan Sulphate, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c-Jun, TGase3, alpha fetoprotein,
Prostate Specific Antigen, erbB2, VEGF, alpha synuclein, Mucin- 1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Tgase 2, Ubiquitin, TLR 4, Cathepsin D, GFAP, RAGE, CD 9, Prostate Acid Phosphatase, Smith Antigen, PRGP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C, Macrophage Scavenger Receptor Type I, Antithrombin, Protein S, BAFF on the calcifying nano-particle. Additionally, proteins that bind to the aforementioned protein list may also become associated with the calcifying nanoparticles. Said proteins may or may not undergo conformational changes. The proteins can be detected by detecting any combination of 7 or fewer of the proteins. The proteins can be detected by detecting any combination of 5 or fewer of the proteins. The proteins can be detected by detecting any combination of 3 or fewer of the proteins. The combination of proteins can be detected in the same assay. The combination of proteins can be detected simultaneously. The combination of proteins can be detected on the same calcifying nano-particle. The combination of proteins can be detected on or within the same device. The combination of proteins detected can constitute a pattern of proteins. The pattern can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination. The pattern can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles. The pattern can identify the type of calcifying nano-particles detected. Disease associated with patholical clarification include, but are not limited to for example, heart or circulatory diseases such as Arteriosclerosis, Atherosclerosis, Coronary Heart Disease, Chronic Heart Failure, Valve Calcifications, Arterial Aneurysms, Calcific Aortic Stenosis, Transient Cerebral Ischemia, Stroke, Peripheral Vascular Disease, Monckeberg's Disease, Vascular Thrombosis; Dental Diseases such as Dental Plaque, Gum Disease (dental pulp stones), calcification of the dentinal papilla, and Salivary Gland Stones; Chronic Infection Syndromes such as Chronic Fatigue Syndrome; Kidney and Bladder Stones, Gall Stones, Pancreas and Bowel Diseases such as Pancreatic Duct Stones, Crohn's Disease, Colitis Ulcerosa; Blood disorders; Adrenal Calcification; Liver Diseases such as Liver Cirrhosis and Liver Cysts; Testicular Microliths, Chronic Calculous Prostatitis, Prostate Calcification, Calcification in Hemodialysis Patients, Malacoplakia; Autoimmune Diseases such as Lupus Erythematosous, Scleroderma, Dermatomyositis, Cutaneous polyarteritis, Panniculitis (Septal and Lobular), Antiphospholipid Syndrome, Arteritis Nodosa, Thrombocytopenia, Hemolytic Anemia, Myelitis, Livedo Reticularis, Chorea, Migraine, Junvenile Dermatomyositis, Graves Disease, Chronic Thyroiditis, Hypothyreoidism, Type 1 Diabetes Mellitis, Addison's Disease, and Hypopituitarism; Placental and Fetal Disorders, Polycystic Kidney Disease, Glomerulopathies; Eye Diseases such as Corneal Calcifications, Cataracts, Macular Degeneration and Retinal Vasculature-derived Processes and other Retinal Degenerations; Retinal Nerve
Degeneration, Retinitis, and Iritis; Ear Diseases such as Otosclerosis, Degeneration of Otoliths and Symptoms from the Vestibular Organ and Inner Ear (Vertigo and Tinnitus); Thyroglossal cysts, Thyroid Cysts, Ovarian Cysts; Cancer such as Meningiomas, Breast Cancer, Prostate Cancer, Thyroid Cancer, Serous Ovarian Adenocarcinoma; Skin diseases such as Calcinosis Cutis, Skin Stones, Calciphylaxis, Psoriasis, Eczema, Lichen Ruber Planus or Lichen Simple Cysts;, Choroid Plexus Calcification, Neuronal Calcification, Calcification of the FaIx Cerebri, Calcification of the Intervertebral Cartilage or Disc, Intercranial or Cerebral Calcification, Rheumatoid Arthritis, Calcific Tenditis, Oseoarthritis, Fibromyalgia, Bone Spurs, Diffuse Interstitial Skeletal Hyperostosis, Intracranial Calcifications such as Degenerative Disease Processes and Dementia;
Erythrocyte-Related Diseases involving Anemia, Intraerythrocytic Nanobacterial Infection and Splenci Calcifications; Chronic Obstructive Pulmonary Disease, Broncholiths, Bronchial Stones, Neuropathy, Calcifications and Encrustations of Implants, Mixed Calcified Biofϊlms, and Myelodegenerative Disorders such as Multiple Sclerosis, Lou Gehrig's, and Alzheimer's Disease.
The proteins can be detected by detecting the presence or absence of any combination of 10 or fewer of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor X/Xa, CDU, Prothrombin, Factor FX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch- 1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamma-Gla residues, TF-VIIa, Complement 3c3, Complement C4, Antichymotrypsin, Annexin V, Lipid A, Isopeptide bond, Vitronectin, Thrombin, Osteocalcin, Troponin T, Vimentin, Tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, Kallikrein 6, Prothrombin Fl, Antithrombin III, Thrombin, Factor VIII, Heparan Sulphate, Factor XI, c-jun, Fra-2, Fra- 1 , Jun B, P-c- Jun, TGase3, alpha fetoprotein, Prostate Specific Antigen, erbB2, VEGF, alpha synuclein, Mucin-1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Tgase 2, Ubiquitin, TLR 4, Cathepsin D, GFAP, RAGE, CD 9, Prostate Acid Phosphatase, Smith Antigen, PRGP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C, Macrophage Scavenger Receptor Type I, Antithrombin, Protein S, BAFF on the calcifying nano- particle. Additionally, proteins that bind to calcium binding proteins may bind to said calcium binding protein/calcifying nano-particles complex including but not limited to Fetuin binding proteins, Thrombin binding proteins, Troponin binding proteins, Tropomyosin binding proteins, GLA Matric binding proteins, Fibrin binding proteins, Kallikrein binding proteins, Factor binding proteins, Matrix metalloprotinease binding proteins, Platelet glycol binding proteins, NF Kappa B binding protein, Factor X binding protein. Table 9 shows representative proteins. Said proteins may or may not undergo conformational changes.
The pattern of the presence or absence of the proteins can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination. The pattern of the presence or absence of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles. The pattern of the presence or absence of the proteins can identify the type of calcifying nano- particles detected. The presence of one or more of the proteins can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination. The presence of one or more of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles. The presence of one or more of the proteins can identify the type of calcifying nano-particles detected. The absence of one or more of the proteins indicates or identifies a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination. The absence of one or more of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles. The absence of one or more of the proteins can identify the type of calcifying nano-particles detected.
Diseases associated with CNPs and pathological calcification include, but are not limimted to, for example, heart or circulatory diseases such as Arteriosclerosis, Atherosclerosis, Coronary Heart Disease, Chronic Heart Failure, Valve Calcifications, Arterial Aneurysms, Calcific Aortic Stenosis, Transient Cerebral Ischemia, Stroke, Peripheral Vascular Disease, Monckeberg's Disease, Vascular Thrombosis; Dental
Diseases such as Dental Plaque, Gum Disease (dental pulp stones), calcification of the dentinal papilla, and Salivary Gland Stones; Chronic Infection Syndromes such as Chronic Fatigue Syndrome; Kidney and Bladder Stones, Gall Stones, Pancreas and Bowel Diseases such as Pancreatic Duct Stones, Crohn's Disease, Colitis Ulcerosa; Blood disorders; Adrenal Calcification; Liver Diseases such as Liver Cirrhosis and Liver Cysts; Testicular Microliths, Chronic Calculous Prostatitis, Prostate Calcification, Calcification in Hemodialysis Patients, Malacoplakia; Autoimmune Diseases such as Lupus Erythematosous, Schleroderma, Dermatomyositis, Cutaneous polyarteritis, Panniculitis (Septal and Lobular), Antiphospholipid Syndrome, Arteritis Nodosa, Thrombocytopenia, Hemolytic Anemia, Myelitis, Livedo Reticularis, Chorea, Migraine, Junvenile
Dermatomyositis, Graves Disease, Chronic Thyroiditis, Hypothyreoidism, Type 1 Diabetes Mellitis, Addison's Disease, and Hypopituitarism; Placental and Fetal Disorders, Polycystic Kidney Disease, Glomerulopathies; Eye Diseases such as Corneal Calcifications, Cataracts, Macular Degeneration and Retinal Vasculature-derived Processes and other Retinal Degenerations; Retinal Nerve Degeneration, Retinitis, and
Iritis; Ear Diseases such as Otosclerosis, Degeneration of Otoliths and Symptoms from the Vestibular Organ and Inner Ear (Vertigo and Tinnitus); Thyroglossal cysts, Thyroid Cysts, Ovarian Cysts; Cancer such as Meningiomas, Breast Cancer, Prostate Cancer, Thyroid Cancer, Serous Ovarian Adenocarcinoma; Skin diseases such as Calcinosis Cutis, Skin Stones, Calciphylaxis, Psoriasis, Eczema, Lichen Ruber Planus or Lichen Simple Cysts;, Choroid Plexus Calcification, Neuronal Calcification, Calcification of the FaIx Cerebri, Calcification of the Intervertebral Cartilage or Disc, Intercranial or Cerebral Calcification, Rheumatoid Arthritis, Calcific Tenditis, Oseoarthritis, Fibromyalgia, Bone Spurs, Diffuse Interstitial Skeletal Hyperostosis, Intracranial Calcifications such as Degenerative Disease Processes and Dementia; Erythrocyte-Related Diseases involving Anemia, Intraerythrocytic Nanobacterial Infection and Splenci Calcifications; Chronic Obstructive Pulmonary Disease, Broncholiths, Bronchial Stones, Neuropathy, Calcifications and Encrustations of Implants, Mixed Calcified Biofilms, and Myelodegenerative Disorders such as Multiple Sclerosis, Lou Gehrig's, and Alzheimer's Disease.
The proteins can be detected using any suitable composition, apparatus, or technique, for example, a microarray, coded beads, flow cytometry, ELISA, mass spectrometry, fluorescence, chemiluminescence, spectrophotometry, chromatography, electrophoresis, or a combination.
Specifically, the disclosed method can use an immunassy detecting approximagtely 100 or fewer difrrerent antigens on the same particles using only one tracer antibody for all of said detected target antigens or epitopes. Thereby utilitizing only one standard curve to provide quantitation of the target antigens and/or epitopes (focused on the use of the antibody). The disclosed method is especially suitable for biogenic particles, such as CNPs, due to stable surface structure due to crosslinking of proteins and binding to the HA. However, the disclosed method is not limited to CNPs. The disclosed method can be utilitzed with viruses, spores, bacteria with stable capsules or similar stable substrate, microparticles in blood, plasma, and the like. Noteably, the particles may be captured using antibodies from any source or based on chemical regions from any source.
The proteins on the calcifying nano-particle can be detected by (a) capturing the calcifying nano-particle, (b) binding a detection compound to one or more of the proteins, and (c) detecting the detection compound. The proteins on the calcifying nano-particle can be detected by (a) binding a detection compound to one or more of the proteins, (b) capturing the calcifying nano-particle, and (c) detecting the detection compound. The calcifying nano-particle can be captured by binding a capture compound to one or more of the proteins, where the capture compound is or becomes immobilized. The proteins to which capture compounds bind can mediate capture, where the detection compound can be bound to one of the proteins, where the calcifying nano-particle can be characterized by determining which proteins mediate capture of the calcifying nano-particle to which the detected detection compound is bound. The capture compound can be bound to one of the proteins, where the detection compounds detected can indicate which of the proteins is present on the calcifying nano-particle, where the calcifying nano-particle can be characterized by which proteins are present on the calcifying nano-particle.
The identified proteins can identify the type of calcifying nano-particle. The identified type of calcifying nano-particle can be related to or associated with a disease or condition. The identified proteins can identify a disease or condition with which calcifying nano-particles having the identified proteins are related or associated. The identified proteins can identify a disease or condition that is caused by calcifying nano- particles having the identified proteins. The identified proteins can identify a disease or condition in which calcifying nano-particles having the identified proteins are produced. Subjects in which pathological thrombosis can occur via apatite-mediated clotting are useful targets for the disclosed methods. Such subjects can include (1) Patients with vulnerable plaque rupture exposing atheroma calcification; (2) Patients undergoing angioplasty or heart-lung machine perfusion; (3) Patients with massive bone fractures or dislocated implants releasing potentially apatite particles; (4) Patients with implants, catheters, wires or stents subject to calcium encrustation; (5) Cancer patients with soft tissue calcification; and (6) Healthy or sick people with CNPs in their blood or positive calcification scores in arteries. A. Protein Detection and Identification
Some forms of the disclosed methods involve detection and/or identification of calcifying nano-particles and/or proteins on calcifying nano-particles. Molecules of interest— including calcifying nano-particles, proteins, and/or proteins in or on a calcifying nano-particle— can be detected using any suitable technique. Molecules of interest to be detected can be in any sample, any composition or any other context. Detection and identification of calcifying nano-particles and proteins on calcifying nano-particles can be facilitated by including labels on the disclosed compounds. Useful labels and their use are described elsewhere herein. Detection of compounds bound to calcifying nano-particles and/or proteins on calcifying nano-particles indicates the presence of the bound calcifying nano-particles and/or proteins on calcifying nano-particles. The disclosed compounds can be detected, for example, via labels on the compounds, by direct detection of the compounds (via an intrinsic feature of the compounds, for example), or by binding a secondary compound to the primary compound and detecting the secondary compound. For this purpose, the secondary compound can include a label. Molecules that interact with or bind to the disclosed calcifying nano-particles and proteins, such as antibodies to a protein, can be detected using known techniques. Many suitable techniques—such as techniques generally known for the detection of proteins, peptides and other analytes and antigens— are known, some of which are described herein. These techniques can involve, for example, direct imaging (for example, microscopy), immunoassays, or functional determination. By "functional determination" is meant that a given protein such as a protein that has a function can be detected by the detection of the function. For example, an enzyme can be detected by evaluating its activity on its substrate. Labeling of proteins and calcifying nano-particles can be either direct or indirect.
In direct labeling, the detecting molecule (the compound that binds the protein of interest such as a detecting compound or capture compound) can include a label. Calcifying nano- particles and/or proteins can be contacted with the labeled molecules (such as detection compounds and capture compounds) under conditions effective and for a period of time sufficient to allow the formation of complexes. The complexes can then be generally washed to remove any non-specifically bound labeled molecules, and the remaining label in the complexes can then be detected. Detection of the label indicates the presence of the detecting molecule which in turn indicates the presence of the protein of interest or other analyte. In indirect labeling, an additional molecule or moiety is brought into contact with, or generated at the site of, the complex of the protein of interest and the detecting molecule. For example, a signal-generating molecule or moiety such as an enzyme can be attached to or associated with the detecting molecule. The signal-generating molecule can then generate a detectable signal at the site of the immunocomplex. For example, an enzyme, when supplied with suitable substrate, can produce a visible or detectable product at the site of the immunocomplex. ELISAs use this type of indirect labeling.
As another example of indirect labeling, an additional molecule (which can be referred to as a binding agent) that can bind to the protein of interest can be contacted with the protein complex. The additional molecule can have a label or signal-generating molecule or moiety. The additional molecule can be termed a secondary molecule or compound. If the secondary molecule is an antibody it can be termed a secondary antibody. The complexes can be contacted with the labeled molecules under conditions effective and for a period of time sufficient to allow the formation of secondary complexes. The secondary complexes can then be generally washed to remove any non- specifically bound labeled secondary molecules, and the remaining label in the secondary complexes can then be detected. The additional molecule can also be or include one of a pair of molecules or moieties that can bind to each other, such as the biotin/avidin pair. In this mode, the detecting molecule can include the other member of the pair. Other modes of indirect labeling include the detection of primary complexes by a two step approach. For example, a molecule (which can be referred to as a first binding agent), such as an antibody, that has binding affinity for the protein of interest can be used to form secondary complexes, as described above. After washing, the secondary complexes can be contacted with another molecule (which can be referred to as a second binding agent) that has binding affinity for the first binding agent, again under conditions effective and for a period of time sufficient to allow the formation of complexes (thus forming tertiary complexes). The second binding agent can be linked to a detectable label or signal-generating molecule or moiety, allowing detection of the tertiary complexes thus formed. This system can provide for signal amplification. Methods for detecting and measuring signals generated by labels are known. For example, radioactive isotopes can be detected by scintillation counting or direct visualization; fluorescent molecules can be detected with fluorescent spectrophotometers; phosphorescent molecules can be detected with a spectrophotometer or directly visualized with a camera; enzymes can be detected by measurement or visualization of the product of a reaction catalyzed by the enzyme; antibodies can be detected by detecting a secondary detection label coupled to the antibody. Such methods can be used directly in the disclosed methods. As used herein, detection molecules are molecules which interact with a molecule of interest (such as a calcifying nano-particle and/or proteins) and to which one or more detection labels are coupled. In another form of detection, labels can be distinguished temporally via different fluorescent, phosphorescent, or chemiluminescent emission lifetimes. Multiplexed time-dependent detection is described in Squire et al., J. Microscopy 197(2):136-149 (2000), and WO 00/08443.
Quantitative measurement of the amount or intensity of a label can be used. For example, quantitation can be used to determine if a given label, and thus the labeled component, is present at a threshold level or amount. A threshold level or amount is any desired level or amount of signal and can be chosen to suit the needs of the particular form of the method being performed. Methods that involve the detection of a substance, such as a protein or an antibody to a specific protein, include label-free assays, protein separation methods (i.e., electrophoresis), solid support capture assays, or in vivo detection. Label-free assays are generally diagnostic means of determining the presence or absence of a specific protein, or an antibody to a specific protein, in a sample. Protein separation methods are additionally useful for evaluating physical properties of the protein, such as size or net charge. Capture assays are generally more useful for quantitatively evaluating the concentration of a specific protein, or antibody to a specific protein, in a sample. Finally, in vivo detection is useful for evaluating the spatial expression patterns of the substance, i.e., where the substance can be found in a subject, tissue or cell.
Assay and detection techniques described herein use various terms, such as antigen, substance, molecule, analyte, etc., to refer molecules of interest that are to be bound or detected. Use of particular terms is not intended to be limiting. Unless the context clearly indicates otherwise, the assays and detection techniques described herein can be used to assay and detect calcifying nano-particles and proteins, such as proteins on calcifying nano-particles and/or proteins on or associated with the proteins on the calcifying nano-particles. As such, the calcifying nano-particles and proteins can be considered the antigen, substance, molecule, analyte, etc. that is bound and/or detected in the assay or detection technique. Assay and detection techniques described herein refer, at various times, to the use of antibodies, such as antibodies that bind to or are specific for antigens, proteins, molecules, etc. Although many forms of the described assays and detection techniques are typically performed using antibodies, the assays and techniques for use in the disclosed methods is not intended to be limiting. Unless the context clearly indicates otherwise, the assays and detection techniques described herein that are described as using (or that commonly used) antibodies can be used with any suitable compound that can bind to the disclosed calcifying nano-particles and proteins. 1. SAPIA
Surface Antigen Pattern Immunoassay (SAPIA) can be used to detect and/or identify stable particles from biological sources and/or components associated thereof. Said components can include, but are not limited to, proteins, peptides, isopeptide bonds, carbohydrates, lipids (fatty acids, phospholipids), endotoxin, heparin sulfate, calcium phosphate, and or nucleic acids (nucleic acid binding proteins associated with HA, amyloid protein P, etc. as associated on the particles.). Examples of stable particles include spores, virus, certain bateria, any colloidal size mineral, metal biological or synthetic material particles (capable of binding antigens to its surface) and calcifying nanoparticles. For example, SAPIA calcifying nano-particles and/or components on calcifying nano-particles. SAPIA allows detection of the presence of multiple proteins on CNPs (Figures 1 A-IE). An example and demonstration of SAPIA is described in the Example 1. In SAPIA, capture compounds, such as antibodies specific for one or more proteins on calcifying nano-particles, are immobilized on a solid support. In some forms, capture compounds specific for multiple proteins on calcifying nano-particles can be situated on a single solid support and/or in an array. SAPIA generally involves capture of calcifying nano-particles on a solid support via binding of one or more proteins on the calcifying nano-particles to capture compounds on the solid support. The captured calcifying nano-particles can then be detected and/or identified by binding a detection compound to the calcifying nano-particles and/or one or more proteins on the calcifying nano-particles and/or one or more of proteins bound to said proteins. In preferred forms of SAPIA, an array of capture compounds specific for different proteins on calcifying nano-particles is used, thus capturing calcifying nano- particles at each array location where a capture compound is present that can bind a protein on the calcifying nano-particles. Because calcifying nano-particles contain a number of proteins, each type of calcifying nano-particle can bind to multiple locations where multiple different capture compounds are present in the array, hi this way detection of the presence of calcifying nano-particles at a given array location can identify a protein on the calcifying nano-particle. Such detection can be accomplished with detection compounds that bind to a single type of protein on calcifying nano-particles because only the presence of calcifying nano-particles needs to be detected. In other forms of SAPIA, capture of calcifying nano-particles can be via a single type of protein on calcifying nano- particles and detection can be via multiple types of proteins on calcifying nano-particles or capture and detection can each be via multiple types of proteins on calcifying nano- particles.
2. Immunoassays Immunodetection methods can be used for detecting, binding, purifying, removing and quantifying various molecules including the disclosed proteins. Further, antibodies and ligands to the disclosed calcifying nano-particles and proteins can be detected. For example, the disclosed proteins can be employed to detect antibodies having reactivity therewith. This is useful, for example, to detect whether a subject has been exposed to or has developed antibodies against a protein. Standard immunological techniques are described, e.g., in Hertzenberg, et al., Weir's Handbook of Experimental Immunology, vols. 1-4 (1996); Coligan, Current Protocols in Immunology (1991); Methods in Enzymology, vols. 70, 73, 74, 84, 92, 93, 108, 116, 121, 132, 150, 162, and 163; and Paul, Fundamental Immunology (3d ed. 1993) each incorporated herein by reference in its entirety and specifically for its teaching regarding immunodetection methods.
The steps of various useful immunodetection methods have been described in the scientific literature, such as, e.g., Maggio et al., Enzyme-Immunoassay, (1987) and Nakamura, et al., Enzyme Immunoassays: Heterogeneous and Homogeneous Systems, Handbook of Experimental Immunology, Vol. 1 : Immunochemistry, 27.1-27.20 (1986) each incorporated herein by reference in its entirety and specifically for its teaching regarding immunodetection methods. Immunoassays, in their most simple and direct sense, are binding assays involving binding between antibodies and antigen. Many types and formats of immunoassays are known and all are suitable for detecting the disclosed proteins. Examples of immunoassays are enzyme linked immunosorbent assays (ELISAs), radioimmunoassays (RIA), radioimmune precipitation assays (RIPA), immunobead capture assays, Western blotting, dot blotting, gel-shift assays, Flow cytometry, protein arrays, multiplexed bead arrays, magnetic capture, in vivo imaging, fluorescence resonance energy transfer (FRET), and fluorescence recovery/localization after photobleaching (FRAP/ FLAP).
In general, immunoassays involve contacting a sample suspected of containing a molecule of interest (such as the disclosed calcifying nano-particles and proteins) with an antibody to the molecule of interest or contacting an antibody to a molecule of interest (such as antibodies to the disclosed proteins) with a molecule that can be bound by the antibody, as the case may be, under conditions effective to allow the formation of immunocomplexes. Contacting a sample with the antibody to the molecule of interest or with the molecule that can be bound by an antibody to the molecule of interest under conditions effective and for a period of time sufficient to allow the formation of immune complexes (primary immune complexes) is generally a matter of simply bringing into contact the molecule or antibody and the sample and incubating the mixture for a period of time long enough for the antibodies to form immune complexes with, i.e., to bind to, any molecules (e.g. antigens) present to which the antibodies can bind, hi many forms of immunoassay, the sample-antibody composition, such as a tissue section, ELISA plate, dot blot or Western blot, can then be washed to remove any non-specifically bound antibody species, allowing only those antibodies specifically bound within the primary immune complexes to be detected. The sample used can be any sample that is suspected of containing a molecule of interest (or an antibody to a molecule of interest). The sample can be, for example, one or more cells, tissue, or bodily fluids such as blood, urine, semen, lymphatic fluid, cerebrospinal fluid, or amniotic fluid, or other biological samples, such as tissue culture cells, buccal swabs, mouthwash, stool, tissue slices, tissue sections, homogenized tissue extract, cell membrane preparation, biopsy aspiration, archeological samples such as bone or mummified tissue, infection samples, nosocomial infection samples, production samples, drug preparation samples, biological molecule production samples, protein preparation samples, lipid preparation samples, and/or carbohydrate preparation samples, and separated or purified forms of any of the above. Such samples can come from subjects or patients.
Immunoassays can include methods for detecting or quantifying the amount of a molecule of interest (such as the disclosed proteins or their antibodies) in a sample, which methods generally involve the detection or quantitation of any immune complexes formed during the binding process. In general, the detection of immunocomplex formation is well known in the art and can be achieved through the application of numerous approaches. These methods are generally based upon the detection of a label or marker, such as any radioactive, fluorescent, biological or enzymatic tags or any other known label. See, for example, U.S. Patents 3,817,837; 3,850,752; 3,939,350; 3,996,345; 4,277,437; 4,275,149 and 4,366,241, each incorporated herein by reference in its entirety and specifically for its teaching regarding immunodetection methods and labels.
Immunoassays that involve the detection of a substance, such as a protein or an antibody to a specific protein, include label-free assays, protein separation methods (i.e., electrophoresis), solid support capture assays, or in vivo detection. Label-free assays are generally diagnostic means of determining the presence or absence of a specific protein, or an antibody to a specific protein, in a sample. Protein separation methods are additionally useful for evaluating physical properties of the protein, such as size or net charge. Capture assays are generally more useful for quantitatively evaluating the concentration of a specific protein, or antibody to a specific protein, in a sample. Finally, in vivo detection is useful for evaluating the spatial expression patterns of the substance, i.e., where the substance can be found in a subject, tissue or cell.
3. Label-free Assays
Provided that the concentrations are sufficient, the molecular complexes can be visible to the naked eye, but smaller amounts may also be detected and measured due to their ability to scatter a beam of light. The formation of complexes indicates that both reactants are present, and in immunoprecipitation assays a constant concentration of a reagent antibody can be used to measure specific antigen and reagent antigens can be used to detect specific antibody. If the reagent species is previously coated onto cells (as in hemagglutination assay) or very small particles (as in latex agglutination assay),
"clumping" of the coated particles is visible at much lower concentrations. A variety of assays based on these elementary principles are in common use, including Ouchterlony immunodiffusion assay, rocket Immunoelectrophoresis, and immunoturbidometric and nephelometric assays. The main limitations of such assays are restricted sensitivity (lower detection limits) in comparison to assays employing labels and, in some cases, the fact that very high concentrations of analyte can actually inhibit complex formation, necessitating safeguards that make the procedures more complex. A variety of instruments can directly detect molecular interactions (binding, for example). Many are based on an evanescent wave on a sensor surface with immobilized ligand, which allows continuous monitoring of binding.
4. Protein Separation
Detection of calcifying nano-particles and/or proteins can involve the separation of the calcifying nano-particles and/or proteins by electophoresis. In two-dimensional electrophoresis, proteins are fractionated first on the basis of one physical property, and, in a second step, on the basis of another. For example, isoelectric focusing can be used for the first dimension, conveniently carried out in a tube gel, and SDS electrophoresis in a slab gel can be used for the second dimension. One example of a procedure is that of O'Farrell, P.H., High Resolution Two-dimensional Electrophoresis of Proteins, J. Biol. Chem. 250:4007-4021 (1975), herein incorporated by reference in its entirety for its teaching regarding two-dimensional electrophoresis methods. Other examples include but are not limited to, those found in Anderson, L and Anderson, NG, High resolution two- dimensional electrophoresis of human plasma proteins, Proc. Natl. Acad. Sci. 74:5421- 5425 (1977), Ornstein, L., Disc electrophoresis, L. Ann. N.Y. Acad. Sci. 121:321349 (1964), each herein incorporated by reference in its entirety for its teaching regarding electrophoresis methods. 5. Western Blot
One example of an immunoassay that uses electrophoresis is Western Blot analysis. Western blotting or immunoblotting allows the determination of the molecular mass of a protein and the measurement of relative amounts of the protein present in different samples. Detection methods include chemiluminescence and chromagenic detection. Standard methods for Western Blot analysis can be found in, for example, D.M. Bollag et al., Protein Methods (2d edition 1996) and E. Harlow & D. Lane, Antibodies, a Laboratory Manual (1988), U.S. Patent 4,452,901, each herein incorporated by reference in their entirety for their teaching regarding Western Blot methods. Generally, proteins are separated by gel electrophoresis, usually SDS-PAGE. The proteins are transferred to a sheet of special blotting paper, e.g., nitrocellulose, though other types of paper, or membranes, can be used. The proteins retain the same pattern of separation they had on the gel. The blot is incubated with a generic protein (such as milk proteins) to bind to any remaining sticky places on the nitrocellulose. An antibody is then added to the solution which is able to bind to its specific protein
The attachment of specific antibodies to specific immobilized antigens can be readily visualized by indirect enzyme immunoassay techniques, usually using a chromogem'c substrate (e.g. alkaline phosphatase or horseradish peroxidase) or chemiluminescent substrates. Other possibilities for probing include the use of fluorescent or radioisotope labels (e.g., fluorescein, T). Probes for the detection of antibody binding can be conjugated anti-immunoglobulins, conjugated staphylococcal Protein A (binds IgG), or probes to biotinylated primary antibodies (e.g., conjugated avidin/ streptavidin). The power of the technique lies in the simultaneous detection of a specific protein by means of its antigenicity, and its molecular mass: proteins are first separated by mass in the SDS-PAGE, then specifically detected in the immunoassay step. Thus, protein standards (ladders) can be run simultaneously in order to approximate molecular mass of the protein of interest in a heterogeneous sample. 6. Capture Assays
Calcifying nano-particles and proteins can be detecting when captured or bound to a solid support (e.g., tube, well, bead, or cell). Examples of such capture assays include Radioimmunoassay (RIA), Enzyme-Linked Immunosorbent Assay (ELISA), Flow cytometry, protein array, multiplexed bead assay, and magnetic capture. i. Radioimmunoassay (RIA)
Radioimmunoassay (RIA) is a quantitative assay for detection of binding complexes using a radioactively labeled substance (radioligand), either directly or indirectly, to measure the binding of the unlabeled substance to a specific antibody or other compound that can bind to the substance. RIA involves mixing a radioactive substance (because of the ease with which iodine atoms can be introduced into tyrosine residues in a protein, the radioactive isotopes 125I or 131I are often used) with antibody or other compound that can bind to the substance. The antibody or other compound is generally linked to a solid support, such as the tube or beads. Unlabeled or "cold" substance is then adding in known quantities and the amount of labeled substance displaced is measured. Initially, the radioactive substance is bound. When cold substance is added, the two compete for binding sites - and at higher concentrations of cold substance, more binds to the antibody or compound, displacing the radioactive variant. The bound substance is separated from the unbound in solution and the radioactivity of each used to plot a binding curve. The technique is both extremely sensitive, and specific. ii. ELISAs Enzyme-Linked Immunosorbent Assay (ELISA), or more generically termed EIA (Enzyme ImmunoAssay), is an immunoassay that can detect an antibody specific for a protein. In such an assay, a detectable label bound to either an antibody-binding or antigen-binding reagent is an enzyme. When exposed to its substrate, this enzyme reacts in such a manner as to produce a chemical moiety which can be detected, for example, by spectrophotometric, fluorometric or visual means. Enzymes which can be used to detectably label reagents useful for detection include, but are not limited to, horseradish peroxidase, alkaline phosphatase, glucose oxidase, /3-galactosidase, ribonuclease, urease, catalase, malate dehydrogenase, staphylococcal nuclease, asparaginase, yeast alcohol dehydrogenase, alpha.-glycerophosphate dehydrogenase, triose phosphate isomerase, glucose-6-phosphate dehydrogenase, glucoamylase and acetylcholinesterase. For descriptions of ELISA procedures, see Voller, A. et al.. J. Clin. Pathol. 31:507-520 (1978); Butler, J. E., Meth. Enzymol. 73:482-523 (1981); Maggio, E. (ed.), Enzyme Immunoassay, CRC Press, Boca Raton, 1980; Butler, J. E., In: Structure of Antigens, Vol. 1 (Van Regenmortel, M., CRC Press, Boca Raton, 1992, pp. 209-259; Butler, J. E., In: van Oss, C. J. et al., (eds), Immunochemistry, Marcel Dekker, Inc., New York, 1994, pp. 759- 803; Butler, J. E. (ed), Immunochemistry of Solid-Phase Immunoassay, CRC Press, Boca Raton, 1991); Crowther, "ELISA: Theory and Practice," In: Methods in Molecule Biology, Vol. 42, Humana Press; New Jersey, 1995. ;U.S. Patent 4,376,110, each incorporated herein by reference in its entirety and specifically for its teaching regarding ELISA methods. ELISA techniques can also be adapted to use compounds, other than antibodies, that bind to molecules of interest.
Variations of ELISA techniques are know to those of skill in the art. In one variation, antibodies that can bind to proteins can be immobilized onto a selected surface exhibiting protein affinity, such as a well in a polystyrene microtiter plate. Then, a test composition suspected of containing a marker antigen can be added to the wells. After binding and washing to remove non-specifically bound immunocomplexes, the bound antigen can be detected. Detection can be achieved by the addition of a second antibody specific for the target protein, which is linked to a detectable label. This type of ELISA is a simple "sandwich ELISA." Detection also can be achieved by the addition of a second antibody, followed by the addition of a third antibody that has binding affinity for the second antibody, with the third antibody being linked to a detectable label.
Another variation is a competition ELISA. In competition ELISA' s, test samples compete for binding with known amounts of labeled antigens or antibodies. The amount of reactive species in the sample can be determined by mixing the sample with the known labeled species before or during incubation with coated wells. The presence of reactive species in the sample acts to reduce the amount of labeled species available for binding to the well and thus reduces the ultimate signal.
Irrespective of the format employed, ELISAs have certain features in common, such as coating, incubating or binding, washing to remove non-specifically bound species, and detecting the bound immunecomplexes. Antigen or antibodies can be linked to a solid support, such as in the form of plate, beads, dipstick, membrane or column matrix, and the sample to be analyzed applied to the immobilized antigen or antibody. In coating a plate with either antigen or antibody, one will generally incubate the wells of the plate with a solution of the antigen or antibody, either overnight or for a specified period of hours. The wells of the plate can then be washed to remove incompletely adsorbed material. Any remaining available surfaces of the wells can then be "coated" with a nonspecific protein that is antigenically neutral with regard to the test antisera. These include bovine serum albumin (BSA), casein and solutions of milk powder. The coating allows for blocking of nonspecific adsorption sites on the immobilizing surface and thus reduces the background caused by nonspecific binding of antisera onto the surface. Such coating and blocking can be used with other capture assays and with other forms of the disclosed methods involving capture and/or solid supports.
In ELISAs, a secondary or tertiary detection means rather than a direct procedure can also be used. Thus, after binding of a protein or antibody to the well, coating with a non-reactive material to reduce background, and washing to remove unbound material, the immobilizing surface is contacted with the control sample to be tested under conditions effective to allow immunecomplex (antigen/antibody) formation. Detection of the immunecomplex then requires a labeled secondary binding agent, or a secondary binding agent in conjunction with a labeled third binding agent.
"Under conditions effective to allow immunecomplex (antigen/antibody) formation" means that the conditions include diluting the antigens and antibodies with solutions such as BSA, bovine gamma globulin (BGG) and phosphate buffered saline (PBS)/Tween. These added agents can also assist in the reduction of nonspecific background.
The "suitable" conditions also mean that the incubation is at a temperature and for a period of time sufficient to allow effective binding. Incubation steps can typically be from about 1 minute to twelve hours, at temperatures of about 20° to 30° C, or can be incubated overnight at about 0° C to about 10° C.
Following all incubation steps in an ELISA, the contacted surface can be washed so as to remove non-complexed material. A washing procedure can include washing with a solution such as PBS/Tween, or borate buffer. Following the formation of specific immunecomplexes between the test sample and the originally bound material, and subsequent washing, the occurrence of even minute amounts of immunecomplexes can be determined.
To provide a detecting means, the second or third antibody can have an associated label to allow detection, as described elsewhere herein. This can be an enzyme that can generate color development upon incubating with an appropriate chromogenic substrate. Thus, for example, one can contact and incubate the first or second immunecomplex with a labeled antibody for a period of time and under conditions that favor the development of further immunecomplex formation (e.g., incubation for 2 hours at room temperature in a PBS-containing solution such as PBS-Tween).
After incubation with the labeled antibody, and subsequent to washing to remove unbound material, the amount of label can be quantified, e.g., by incubation with a chromogenic substrate such as urea and bromocresol purple or 2,2'-azido-di-(3-ethyl- benzthiazoline-6-sulfonic acid [ABTS] and H2O2, in the case of peroxidase as the enzyme label. Quantitation can then be achieved by measuring the degree of color generation, e.g., using a visible spectra spectrophotometer. iii. Flow Cytometry Flow cytometry, fluorescent activated cell sorting (FACS), fluorescence activated sorting, and flow microfluorometry provide a means of scanning individual cells or particles for the presence of a molecule of interest. Although commonly used for analysis of cells, these techniques can be used in the disclosed method to detect, analyze and identify calcifying nano-particles and/or proteins on calcifying nano-particles. Flow Cytometry is the characterization of single cells or particles as they pass at high speed through a laser beam. While a hematologist can count 200 cells in less than a minute by hand (hemocytometer) on a stage microscope, a flow cytometer can discriminate cells at speeds up to 50,000 cells/second. The Flow component is a fluidics system that precisely delivers the cells at the intersection of the laser beam and light gathering lens by hydrodynamic focusing (a single stream of cells is injected and confined within an outer stream at greater pressure). The laser acting as a light source develops parameters of light scatter as well as exciting the fluorescent molecules used to label the cell. Cells are characterized individually by their physical and/or chemical properties (Kohler, G. and Milstein, C. (1975) Continuous Cultures of Fused Cells Secreting Antibody of Predefined Specificity. Nature 256: p. 495-49) which provide analytical parameters capable of accurate quantitation of the number of molecules/cell through Quantitative Flow Cytometry (QFCM). The physical (morphological) profile of a cell or particle can be observed by combining forward light scatter (FS) and orthogonal or side light scatter (SSC). In forward light scatter the laser beam is interrupted by the cell or particle and the light that passes around the cell or particle is measured. Comparable to casting shadow puppets on a wall with a flashlight. This measurement is an indication of the cell's or particle's unique refractive index. Side scatter is the light that is reflected 90° to the laser beam (all fluorescence is emitted and therefore collected at this angle) and is an indication of density or surface granularity.
A short list of some of the information that can be discerned by multiparameter (multi-color) Flow Cytometry includes; Apoptosis (programmed cell death), Cell Type, DNA Content, Enzyme Activity, Intracellular Proteins, Cell Surface Antigens,
Cytoplasmic Granularity, Surface Membrane Integrity, Intracellular [Ca++]-Signal Transduction, DNA Synthesis-Proliferation, Cell Surface Receptors, Intracellular Cytokines, Oxidative Metabolism, Intracellular pH, RNA Content, and Cell Size.
Antibodies can provide a useful tool for the analysis and quantitation of markers of individual cells. Such flow cytometric analyses are described in Melamed, et al., Flow Cytometry and Sorting (1990); Shapiro, Practical Flow Cytometry (1988); and Robinson, et al., Handbook of Flow Cytometry Methods (1993), each herein incorporated by reference in its entirety for their teaching regarding FACS. Generally, proteins are detected with antibodies that have been conjugated to fluorescent molecules such as FITC, PE, Texas Red, APC, etc. Molecules on the cell or particle surface can be detected.
By tagging antibodies with a colored fluorochrome, it is easy to distinguish the presence and quantity of antigens on particles or cells. Employing dichroic splitting mirrors, band pass filters and compensation, the colors can be resolved where each color is associated with a single antibody. As each cell or particle, tagged with a fluorescently labeled antibody, enters the laser light outer orbital electrons in the fluorochrome are excited at a specific excitation wavelength (e.g., 494 nm for FITC). As it transitions the width of the laser beam maximum peak fluorescence is achieved within approximately 10 nsec as the excited outer orbital electrons return to their more stable ground state and emit a photon of light at a longer wavelength (e.g., 520 nm for FITC) than that at which they were excited. Photomultiplier tubes (PMT's) detect these faint fluorescent signals and their sole role is to change discrete packets of light called photons (hv) into electrons and amplify them by producing as much as 10 million electrons for every photon captured.
Fluorescence-activated cell sorting (FACS) and fluorescence-activated sorting are types of flow cytometry. FACS is a method for sorting a suspension of biologic cells into two or more containers, one cell at a time. FACS can also be performed on particles such as calcifying nano-particles (in which case it can be referred to as fluorescence-activated sorting). Fluorescence-activated cell sorting is based upon specific light scattering and fluorescence characteristics of each cell or particle. In FACS, the cell or particle suspension is entrained in the center of a narrow, rapidly flowing stream of liquid. The flow is arranged so that there is a large separation between cells and particles relative to their diameter. A vibrating mechanism causes the stream of cells and particles to break into individual droplets. The system is adjusted so that there is a low probability of more than one cell or particle being in a droplet. Just before the stream breaks into droplets the flow passes through a fluorescence measuring station where the fluorescence character of interest of each cell or particle is measured. An electrical charging ring is placed just at the point where the stream breaks into droplets. A charge is placed on the ring based on the immediately prior fluorescence intensity measurement and the opposite charge is trapped on the droplet as it breaks from the stream. The charged droplets then fall through an electrostatic deflection system that diverts droplets into containers based upon their charge. iv. Protein Arrays
Protein arrays are solid-phase ligand binding assay systems using immobilised proteins on surfaces which include glass, membranes, microtiter wells, mass spectrometer plates, and beads or other particles. The assays are highly parallel (multiplexed) and often miniaturised (microarrays, protein chips). Their advantages include being rapid and automatable, capable of high sensitivity, economical on reagents, and giving an abundance of data for a single experiment. Bioinformatics support is important; the data handling demands sophisticated software and data comparison analysis. However, the software can be adapted from that used for DNA arrays, as can much of the hardware and detection systems. Such systems and techniques of protein arrays can be used to detect calcifying nano-particles and/or proteins on calcifying nano-particles.
One of the chief formats is the capture array, in which ligand-binding reagents, which are usually antibodies but can also be alternative protein scaffolds, peptides or nucleic acid aptamers, are used to detect target molecules in mixtures such as plasma or tissue extracts. In diagnostics, capture arrays can be used to carry out multiple immunoassays in parallel, both testing for several analytes in individual sera for example and testing many serum samples simultaneously. In proteomics, capture arrays are used to quantitate and compare the levels of proteins in different samples in health and disease, i.e. protein expression profiling. Proteins other than specific ligand binders are used in the array format for in vitro functional interaction screens such as protein-protein, protein- DNA, protein-drug, receptor-ligand, enzyme-substrate, etc. They may also be used to correlate the polymorphic changes resulting from SNPs with protein function. The capture reagents themselves are selected and screened against many proteins, which can also be done in a multiplex array format against multiple protein targets. Analysis of multiple proteins on calcifying nano-particles can be performed using such techniques. For construction of arrays, sources of proteins include cell-based expression systems for recombinant proteins, purification from natural sources, production in vitro by cell-free translation systems, and synthetic methods for peptides. Many of these methods can be automated for high throughput production. For capture arrays and protein function analysis, it is important that proteins should be correctly folded and functional; this is not always the case, e.g. where recombinant proteins are extracted from bacteria under denaturing conditions. Nevertheless, arrays of denatured proteins are useful in screening antibodies for cross-reactivity, identifying autoantibodies and selecting ligand binding proteins.
Protein arrays have been designed as a miniaturisation of familiar immunoassay methods such as ELISA and dot blotting, often utilizing fluorescent readout, and facilitated by robotics and high throughput detection systems to enable multiple assays to be carried out in parallel. Commonly used physical supports include glass slides, silicon, microwells, nitrocellulose or PVDF membranes, and magnetic and other microbeads. While microdrops of protein delivered onto planar surfaces are the most familiar format, alternative architectures include CD centrifugation devices based on developments in microfluidics [Gyros] and specialised chip designs, such as engineered microchannels in a plate [The Living Chip™, Biotrove] and tiny 3D posts on a silicon surface [Zyomyx]. Particles in suspension can also be used as the basis of arrays, providing they are coded for identification; systems include color coding for microbeads [Luminex, Bio-Rad] and semiconductor nanocrystals [QDots™, Quantum Dots], and barcoding for beads [UltraPlex™, Smartbeads] and multimetal microrods [Nanobarcodes™ particles, Nanoplex Technologies]. Beads can also be assembled into planar arrays on semiconductor chips [LEAPS technology, Bio Array Solutions].
Immobilization of proteins involves both the coupling reagent and the nature of the surface being coupled to. A good protein array support surface is chemically stable before and after the coupling procedures, allows good spot morphology, displays minimal nonspecific binding, does not contribute a background in detection systems, and is compatible with different detection systems. The immobilization method used are reproducible, applicable to proteins of different properties (size, hydrophilic, hydrophobic), amenable to high throughput and automation, and compatible with retention of fully functional protein activity. Orientation of the surface-bound protein is recognized as an important factor in presenting it to ligand or substrate in an active state; for capture arrays the most efficient binding results are obtained with orientated capture reagents, which generally require site-specific labeling of the protein.
Both covalent and noncovalent methods of protein immobilization are used and have various pros and cons. Passive adsorption to surfaces is methodologically simple, but allows little quantitative or orientational control; it may or may not alter the functional properties of the protein, and reproducibility and efficiency are variable. Covalent coupling methods provide a stable linkage, can be applied to a range of proteins and have good reproducibility; however, orientation may be variable, chemical derivatization may alter the function of the protein and requires a stable interactive surface. Biological capture methods utilizing a tag on the protein provide a stable linkage and bind the protein specifically and in reproducible orientation, but the biological reagent must first be immobilized adequately and the array may require special handling and have variable stability.
Several immobilization chemistries and tags have been described for fabrication of protein arrays. Substrates for covalent attachment include glass slides coated with amino- or aldehyde-containing silane reagents. In the Versalinx™ system [Prolinx], reversible covalent coupling is achieved by interaction between the protein derivatised with phenyldiboronic acid, and salicylhydroxamic acid immobilized on the support surface. This also has low background binding and low intrinsic fluorescence and allows the immobilized proteins to retain function. Noncovalent binding of unmodified protein occurs within porous structures such as HydroGel™ [PerkinElmer], based on a 3- dimensional polyacrylamide gel; this substrate is reported to give a particularly low background on glass microarrays, with a high capacity and retention of protein function. Widely used biological coupling methods are through biotin/streptavidin or hexahistidine/Ni interactions, having modified the protein appropriately. Biotin may be conjugated to a poly-lysine backbone immobilised on a surface such as titanium dioxide [Zyomyx] or tantalum pentoxide [Zeptosens].
Array fabrication methods include robotic contact printing, ink-jetting, piezoelectric spotting and photolithography. A number of commercial arrayers are available [e.g. Packard Biosience] as well as manual equipment [V & P Scientific]. Bacterial colonies can be robotically gridded onto PVDF membranes for induction of protein expression in situ.
At the limit of spot size and density are nanoarrays, with spots on the nanometer spatial scale, enabling thousands of reactions to be performed on a single chip less than lmm square. BioForce Laboratories have developed nanoarrays with 1521 protein spots in 85 sq microns, equivalent to 25 million spots per sq cm, at the limit for optical detection; their readout methods are fluorescence and atomic force microscopy (AFM).
Fluorescence labeling and detection methods are widely used. The same instrumentation as used for reading DNA microarrays is applicable to protein arrays. For differential display, capture (e.g. antibody) arrays can be probed with fluorescently labeled proteins from two different cell states, in which cell lysates are directly conjugated with different fluorophores (e.g. Cy-3, Cy-5) and mixed, such that the color acts as a readout for changes in target abundance. Fluorescent readout sensitivity can be amplified 10-100 fold by tyramide signal amplification (TSA) [PerkinElmer Lifesciences]. Planar waveguide technology [Zeptosens] enables ultrasensitive fluorescence detection, with the additional advantage of no intervening washing procedures. High sensitivity can also be achieved with suspension beads and particles, using phycoerythrin as label [Luminex] or the properties of semiconductor nanocrystals [Quantum Dot]. A number of novel alternative readouts have been developed, especially in the commercial biotech arena. These include adaptations of surface plasmon resonance [HTS Biosystems, Intrinsic Bioprobes], rolling circle DNA amplification [Molecular Staging], mass spectrometry [Ciphergen, Intrinsic Bioprobes], resonance light scattering [Genicon Sciences] and atomic force microscopy [BioForce Laboratories]. Capture arrays form the basis of diagnostic chips and arrays for expression profiling. They employ high affinity capture reagents, such as conventional antibodies, single domains, engineered scaffolds, peptides or nucleic acid aptamers, to bind and detect specific target ligands in high throughput manner.
Antibody arrays have the required properties of specificity and acceptable background, and some are available commercially [BD Biosciences Clontech, BioRad, Sigma]. Antibodies for capture arrays are made either by conventional immunisation (polyclonal sera and hybridomas), or as recombinant fragments, usually expressed in E. coli, after selection from phage or ribosome display libraries [Cambridge Antibody Technology, Biolnvent, Affϊtech, Biosite]. In addition to the conventional antibodies, Fab and scFv fragments, single V-domains from camelids or engineered human equivalents [Domantis] may also be useful in arrays.
The term 'scaffold' refers to ligand-binding domains of proteins, which are engineered into multiple variants capable of binding diverse target molecules with antibody-like properties of specificity and affinity. The variants can be produced in a genetic library format and selected against individual targets by phage, bacterial or ribosome display. Such ligand-binding scaffolds or frameworks include 'Affibodies' based on Staph, aureus protein A [Affibody], 'Trinectins' based on fibronectins [Phylos] and 'Anticalins' based on the lipocalin structure [Pieris]. These can be used on capture arrays in a similar fashion to antibodies and may have advantages of robustness and ease of production.
Non-protein capture molecules, notably the single-stranded nucleic acid aptamers which bind protein ligands with high specificity and affinity, are also used in arrays [SomaLogic]. Aptamers are selected from libraries of oligonucleotides by the Selex™ procedure and their interaction with protein can be enhanced by covalent attachment, through incorporation of brominated deoxyuridine and UV-activated crosslinking (photoaptamers). Photocrosslinking to ligand reduces the crossreactivity of aptamers due to the specific steric requirements. Aptamers have the advantages of ease of production by automated oligonucleotide synthesis and the stability and robustness of DNA; on photoaptamer arrays, universal fluorescent protein stains can be used to detect binding.
Protein analytes binding to antibody arrays may be detected directly or via a secondary antibody in a sandwich assay. Direct labeling is used for comparison of different samples with different colors. Where pairs of antibodies directed at the same protein ligand are available, sandwich immunoassays provide high specificity and sensitivity and are therefore the method of choice for low abundance proteins such as cytokines; they also give the possibility of detection of protein modifications. Label- free detection methods, including mass spectrometry, surface plasmon resonance and atomic force microscopy, avoid alteration of ligand. An alternative to an array of capture molecules is one made through 'molecular imprinting' technology, in which peptides (e.g. from the C-terminal regions of proteins) are used as templates to generate structurally complementary, sequence-specific cavities in a polymerisable matrix; the cavities can then specifically capture (denatured) proteins which have the appropriate primary amino acid sequence [ProteinPrint™, Aspira Biosystems].
Another methodology which can be used diagnostically and in expression profiling is the ProteinChip® array [Ciphergen], in which solid phase chromatographic surfaces bind proteins with similar characteristics of charge or hydrophobicity from mixtures such as plasma or tumour extracts, and SELDI-TOF mass spectrometry is used to detection the retained proteins. This technology differs from the protein arrays under discussion here since, in general, it does not involve immobilization of individual proteins for detection of specific ligand interactions. For detecting protein-protein interactions, protein arrays can be in vitro alternatives to the cell-based yeast two-hybrid system and may be useful where the latter is deficient, such as interactions involving secreted proteins or proteins with disulphide bridges. High- throughput analysis of biochemical activities on arrays has been described for yeast protein kinases and for various functions (protein-protein and protein-lipid interactions) of the yeast proteome, where a large proportion of all yeast open-reading frames was expressed and immobilised on a microarray. v. Multiplexed Bead Assay
A multiplexed bead assay, such as for example the BD™ Cytometric Bead Array, is a series of spectrally discrete particles that can be used to capture and quantitate soluble analytes. The analyte is then measured by detection of a fluorescence-based emission and flow cytometric analysis. Multiplexed bead assay generates data that is comparable to ELISA based assays, but in a "multiplexed" or simultaneous fashion. Concentration of unknowns is calculated for the cytometric bead array as with any sandwich format assay, i.e. through the use of known standards and plotting unknowns against a standard curve. Further, multiplexed bead assay allows quantification of soluble analytes in samples never previously considered due to sample volume limitations, hi addition to the quantitative data, powerful visual images can be generated revealing unique profiles or signatures that provide the user with additional information at a glance. vi. Magnetic Capture Antibody-coated magnetic particles can be used to capture and selectively separate analytes, such as calcifying nano-particles, from solution. In the technique, target-specific antibody is bound to a magnetic particle (often termed an immunobead). After reaction time to allow binding of immunobead and target, a strong magnetic field is applied to selectively separate the captured target-particle complexes from the milieu. 7. Imunocytochemistry/ immunohistochemistry
Also provided are methods of detecting a substance of interest such as a protein in vivo or in situ using antibody conjugates. Imunocytochemistry and immunohistochemistry are techniques for identifying cellular or tissue constituents, respectively, by means of antigen-antibody interactions. The methods generally involve administering to an animal or subject an imaging-effective amount of a detectably-labeled protein-specific antibody or fragment thereof, and then detecting the location of the labeled antibody in the sample cell or tissue. An "imaging effective amount" is an amount of a detectably-labeled antibody, or fragment thereof, that when administered is sufficient to enable later detection of binding of the antibody or fragment in the specific cell or tissue. The effective amount of the antibody-marker conjugate is allowed sufficient time to come into contact with reactive antigens that are present within the tissues of the subject, and the subject is then exposed to a detection device to identify the detectable marker.
Antibody conjugates or constructs for imaging thus have the ability to provide an image of the tissue, for example, through fluorescence microscopy, laser scanning confocal microscopy (LSCM), magnetic resonance imaging (MRT), SEM, TEM, x-ray imaging, computerized emission tomography and the like. Fluorescence microscopy and laser scanning confocal microscopy (LSCM) involve the detection of fluorochrome labels, such as those provided herein. Wide-field fluorescence microscopy is a very widely used technique to obtain both topographical and dynamic information. It relies on the simultaneous illumination of the whole sample. The source of light is usually a mercury lamp, giving out pure white light. Optical filters are then used in order to select the wavelength of excitation light (the excitation filter).
Excitation light is directed to the sample via a dichroic mirror (i.e., a mirror that reflects some wavelengths but is transparent to others) and fluorescent light detected by a camera (usually a CCD camera). Thus both the illumination and detection of light covering the whole visual field of the chosen microscope objective is achieved simultaneously. LSCM differs from wide-field fluorescence microscopy in a number of ways. The light source in LSCM is one or more laser(s). This has two consequences. Firstly, the excitation light bandwidth is determined by the source, not the excitation filter and thus is much narrower than in fluorescence microscopy (2-3 nm rather than 20 - 30 nm). Secondly, in order to illuminate the whole visual field, the laser beam has to be rapidly scanned across the area in a series of lines, much like a TV image is generated. The fluorescence detected at each point is measured in a photomultiplier tube (PMT) and an image built up. The major difference between fluorescence microscopy and LSCM, however, is the pinhole, which is a device that removes unwanted, out-of-focus fluorescence, giving an optical slice of a 3-dimensional image. This "optical slicing" allows the observer to see inside the object of interest and gives clearer images, with more fine detail observable. This method of illumination also has advantages in that it is possible to illuminate selected regions of the visual field allowing complex photobleaching protocols to be carried out to investigate the rates of lateral travel of fluorophores, etc. and for the excitation of different fluorophores in different regions of the same cell. In addition, by altering the focus of the microscope, images can be obtained at different depths. Each image is called a z-section, and can be used to reconstruct an image of the 3- dimensional object. Multi-Photon LSCM is a variation of LSCM that involves the generation of high energy fluorescence using low energy incident light. This is achieved by delivering multiple photons of excitation light to the same point in space in a sufficiently short time that the energy effectively is summed and so acts as a higher energy single photon. The lasers required for this technique are very specialized and very expensive; however, there are a number of advantages of using multiphoton LSCM over conventional techniques. Firstly, high intensity red light scatters less than low intensity blue light, so objects of interest can be imaged in thicker sections of tissue than in conventional LSCM. Thicker slices are likely to be healthier, and the cells being observed are less likely to have been damaged in the preparation of the sample. Secondly, the lower overall energy of the excitation light means that less phototoxic damage is caused during viewing and less photobleaching is seen, extending the time that cells can be observed. Thirdly, multiphoton LSCM is innately confocal, i.e., no pinhole is required. Excitation of the fluorophore can only occur where the two photons can interact. Given the quadratic nature of the probability of two photons interacting with the fluorophore in the necessary timescale, excitation only occurs in the focal plane of the objective lens, which provides cleaner images.
Elements particularly useful in MPJ include the nuclear magnetic spin-resonance isotopes 157Gd, 55Mn, 162Dy, 52Cr, and 56Fe, with gadolinium often being preferred. Radioactive substances, such as technicium99"1 or indium π, that can be detected using a gamma scintillation camera or detector, also can be used. Further examples of metallic ions suitable for use in the current methods are 1231, 131I, 97Ru, 67Cu, 67Ga, 1251, 68Ga, 72As, 89Zr, and 201Tl. A radionuclide can be bound to an antibody either directly or indirectly by using an intermediary functional group. Intermediary functional groups which are often used to bind radioisotopes which exist as metallic ions to antibody are diethylenetriaminepentaacetic acid (DTPA) and ethylene diaminetetracetic acid (EDTA). Administration of the antibodies can be done as disclosed herein. Nucleic acid approaches for antibody delivery also exist. Antibodies and antibody fragments can also be administered to patients or subjects as a nucleic acid preparation (e.g., DNA or RNA) that encodes the antibody or antibody fragment, such that the patient's or subject's own cells take up the nucleic acid and produce and secrete the encoded antibody or antibody fragment. The delivery of the nucleic acid can be by any means, as disclosed herein, for example. Administration of the antibody can be local or systemic and accomplished intravenously, intra-arterially, via the spinal fluid or the like. Administration also can be intradermal or intracavitary, depending upon the body site under examination. After a sufficient time has lapsed for the labeled antibody or fragment to bind to the diseased tissue, for example 30 minutes to 48 hours, the area of the subject under investigation can then be examined by an imaging technique, such as those described herein.
The distribution of the bound radioactive isotope and its increase or decrease with time can be monitored and recorded. By comparing the results with data obtained from studies of clinically normal individuals, the presence and extent of the diseased tissue can be determined. The exact imaging protocol will necessarily vary depending upon factors specific to the subject, and depending upon the body site under examination, method of administration, type of label used and the like. One of ordinary skill in the art will be able to determine which imaging protocol to use based on these factors. Effective dosages and schedules for administering the compositions can be determined empirically, and making such determinations is within the skill in the art. The dosage ranges for the administration of the compositions are those large enough to produce the desired effect in which the symptoms of the disorder are affected. The dosage should not be so large as to cause adverse side effects, such as unwanted cross-reactions, anaphylactic reactions, and the like. Generally, the dosage will vary with the age, condition, sex and extent of the disease in the patient, route of administration, or whether other drugs are included in the regimen, and can be determined by one of skill in the art. The dosage can be adjusted by the individual physician in the event of any counterindications. Dosage can vary, and can be administered in one or more dose administrations daily, for one or several days. Guidance can be found in the literature for appropriate dosages for given classes of pharmaceutical products. For example, guidance in selecting appropriate doses for antibodies can be found in the literature on therapeutic uses of antibodies, e.g., Ferrone et al., Handbook of Monoclonal Antibodies, (1985) ch. 22 and pp. 303-357; Haber et al., Antibodies in Human Diagnosis and Therapy, (1977) pp. 365-389. A typical daily dosage of the antibody used alone might range from about 1 μg/kg to up to 100 mg/kg of body weight or more per day, depending on the factors mentioned above.
As used herein, "FRET" relates to the phenomenon known as "fluorescence resonance energy transfer". The principle of FRET has been described for example in J.R. Lakowicz, "Principles of Fluorescence Spectroscopy", 2 (nd) Ed. Plenum Press, New York, 1999. Briefly, FRET can occur if the emission spectrum of a first chromophore (donor chromophore or FRET-donor) overlaps with the absorption spectrum of a second chromophore (acceptor chromophore or FRET-acceptor), so that excitation by lower- wavelength light of the donor chromophore is followed by transfer of the excitation energy to the acceptor chromophore. A prerequisite for this phenomenon is the very close proximity of both chromophores. A result of FRET is the decrease/loss of emission by the donor chromophore while at the same time emission by the acceptor chromophore is observed. A further result of FRET is shortening of the duration of the donor excited state as detected by a reduction in the fluorescence lifetime. A pair of 2 chromophores which can interact in the above described manner is called a "donor-acceptor-pair" for FRET.
In FRET, the energy stored in the excited state of a fluorophore (the donor) upon absorption of a photon, is transferred non-radiatively to a second fluorophore (or chromophore), the acceptor. This transfer is due to dipole-dipole interactions between the emission dipole of the donor and the absorption dipole of the acceptor and depends on the separation distance, the orientation between the dipoles, and the extent of overlapping energy levels (the overlap integral). The inverse sixth order dependence of FRET on separation distance produces an extremely steep decline of the FRET efficiency over a couple of nanometers. Furthermore, the typical distance for most pairs at which 50% of the molecules engage in FRET (the Foerster or RO distance) lies in the order of magnitude of average protein diameter (4-6 nm), giving rise to detectable FRET at a maximum distance of about 10 nm.
For the latter reason, FRET is a very popular method to assess (fluorescently labeled) protein-protein interactions and protein conformational changes. Thus, FRET can be used to detect calcifying nano-particles and/or proteins on calcifying nano-particles.
A number of techniques are available at present to detect and quantify the occurrence of FRET. These fall into two categories: 1) Spectral, i.e. fluorescence emission intensity-based methods that are based on the loss of donor emission and concomitant gain of acceptor emission. These are: sensitized acceptor emission, ratio imaging, acceptor photobleaching-induced donor unquenching, and anisotropy microscopy. 2) Fluorescence decay kinetics-based methods that are based on the reduced donor photobleaching phenomenon and reduced donor fluorescence lifetime (or duration of the excited state) in the presence of FRET. These are: donor photobleaching kinetics and fluorescence lifetime imaging microscopy (FLEVl). The latter technique is especially useful for FRET as the fluorescence lifetime is relatively independent of trivial non-FRET related events and is furthermore independent of fluorophore concentration and light path, both of which are difficult to control in a microscope. Different, functionally equivalent implementations of FLBVI exist (Szmacinski et al. (1994) "Fluorescence lifetime imaging microscopy: homodyne technique using high- speed gated image intensifier." Methods
Enzymol, 240:723-48; Wang et al. (1992) Crit Rev Anal Chem, 23 (5): 369-395; Clegg et al. (2003) Methods Enzymol, 360:509-42; Theodoras et al (1993) Biophys. Chem. Volume 48, Issue 2, Dec.1993, pp. 221-239. )
FRAP (Reits andNeefjes (2001) Nat Cell Biol,Jwi;3(6) :E145-7) is a technique that reports on diffusion of fluorescently labeled biomolecules in living cells. In this technique, a high-power laser beam is used to photodestruct labeled biomolecules in a defined area of the cell. Diffusion (and transport) of molecules from neighboring non- illuminated areas can then repopulate the illuminated area, leading to a time-dependent recovery of fluorescence in this area. For the recovery kinetics, the diffusional recovery can be determined. In another implementation called fluorescence loss in photobleaching (FLIP), the high-power laser illuminates the same area in the cell for a longer period. Diffusionally connected areas in the cell, outside of the illuminated area will loose total fluorescence intensity due to continuous delivery and photodestruction in the illuminated area. FRAP and FLIP can be used to detect and follow the movements of calcifying nano- particles.
A recent implementation of FRAP called fluorescence localization after photobleaching (FLAP) (Dunn et al. (2002) J Microsc, Jan;205(Pt 1): 109-12) uses two spectrally separated fluorescently labeled forms of the same biomolecule where only one of the fluorescent species is photodestructed, either in the short-term FRAP or long-term FLIP mode. The non-destructed fluorescent species now acts as reference and diffusion/transport of the biomolecule can be assessed by simple division of the two fluorescent emission bands. The loss of the photodestructed species leads to a detectable change in the image ratio and provides, in addition to diffusional velocity parameters, information on the directionality of the diffusion/transport process. The same effect can be achieved when using photoconvertible or photoactivatable fluorescent protein tags (Zhang et al. (2002) Nat Rev MoI Cell Biol, Dec;3(12):906-18). This technique is particularly suited to detection of calcifying nano-particles. Specific Embodiments
Disclosed is a method for detecting calcifying nano-particles, the method comprising detecting calcifying nano-particles by detecting one or more proteins on the calcifying nano-particles.
Also disclosed is a method for detecting one or more proteins, the method comprising detecting one or more proteins on a calcifying nano-particle.
Also disclosed is a method of characterizing a calcifying nano-particle, the method comprising identifying one or more proteins on a calcifying nano-particle.
Also disclosed is a method of diagnosing a disease or condition, the method comprising identifying one or more proteins on a calcifying nano-particle from a subject, wherein the identified proteins identify a disease or condition with which calcifying nano- particles having the identified proteins are related or associated.
Also disclosed is a method of assessing the prognosis of a disease or condition, the method comprising identifying one or more proteins on a calcifying nano-particle from a subject, wherein the identified proteins identify calcifying nano-particles that are related to or associated with the prognosis of the disease or condition.
Also disclosed is a method of identifying a subject at risk of a disease or condition, the method comprising identifying one or more proteins on a calcifying nano-particle from a subject, wherein the identified proteins identify calcifying nano-particles that are related to or associated with a risk of developing a disease or condition.
Also disclosed is an isolated calcifying nano-particle, wherein the calcifying nano- particle comprises one or more of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor X/Xa, CD14, Prothrombin, Factor IX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CPvP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch-1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamma-Gla residues, TF-VIIa, Complement 3c3, Complement C4, Antichymotrypsin, Annexin V, Lipid A, Isopeptide bond, Vitronectin, Thrombin, Osteocalcin, Troponin T, Vimentin, Tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, Kallikrein 6, Prothrombin Fl, Antithrombin III, Thrombin, Factor VIII, Heparan Sulphate, Factor XI, c-jun, Fra-2, Fra- 1 , Jun B, P-c- Jun, TGase3, alpha fetoprotein, Prostate Specific Antigen, erbB2, VEGF, alpha synuclein, Mucin-1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Tgase 2, Ubiquitin, TLR 4, Cathepsin D, GFAP, RAGE, CD 9, Prostate Acid Phosphatase, Smith Antigen, PRGP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C, Macrophage Scavenger Receptor Type I5 Antithrombin, Protein S, BAFF on the calcifying nano- particle. In addition, binding proteins to the aforementioned protoein list can bind to the associated proteins. Proteins may or may not undergo a primary and/or secondary conformational change.
Also disclosed is a composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that collects said calcium binding proteins.
Also disclosed is a compositon comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that has calcium binding proteins associated thereon and proteins that bind to said calcium binding proteins .
Also disclosed is a composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating that has calcium binding proteins associated thereon wherein said calcium binding proteins undergo a primary conformation change as a result of said association
Also disclosed is a composition comprising a calcifying nano-particle where the calcifying nano-particle is covered in a hydroxy apatite (calcium phosphate mineral) coating containing bound calcium binding binding proteins that may experience conformational changes and wherein secondary bound proteins thereon experience conformational changes.
Also disclosed is a composition comprising a calcifying nano-particle and one or more compounds bound to one or more proteins on the calcifying nano-particle. Also disclosed is a method of determining the progress of treatment of a subj ect having calcifying nano-particles, the method comprising detecting one or more proteins on calcifying nano-particles in a sample from the subject, and repeating the detection in another sample from the subject following treatment, wherein a change in the level, amount, concentration, or a combination of calcifying nano-particles in the subject indicates the progress of the treatment of the subject.
Also disclosed herein are compositions comprising apatite and a coating material, where, for example, the coating material limits exposure of the blood of a subject when the composition is in a subject.
Also disclosed herein is a method of testing biocompatibility comprising testing blood coagulation in the absence of anticoagulants and a method of testing materials that will be exposed to circulating blood for formation of calcific biofilm formation.
The calcifying nano-particles can be detected by detecting one or more of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor X/Xa, CD 14, Prothrombin, Factor IX, Fetuin B, CD40,
Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch- 1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamma-Gla residues, TF-VTIa, Complement 3c3, Complement C4, Antichymotrypsin, Annexin V, Lipid A, Isopeptide bond, Vitronectin, Thrombin, Osteocalcin, Troponin T, Vimentin, Tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, Kallikrein 6, Prothrombin Fl, Antithrombin III, Thrombin, Factor VIII, Heparan Sulphate, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c-Jun, TGase3, alpha fetoprotein, Prostate Specific Antigen, erbB2, VEGF, alpha synuclein, Mucin- 1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Tgase 2, Ubiquitin, TLR 4, Cathepsin D, GFAP, RAGE, CD 9, Prostate Acid Phosphatase, Smith Antigen, PRGP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C Macrophage Scavenger Receptor Type I, Antithrombin, Protein S, BAFF on the calcifying nano-particles.
The calcifying nano-particles can be detected by detecting two or more proteins on the calcifying nano-particles. The calcifying nano-particles can be detected by detecting one or more proteins with a GLA-containing domain. The calcifying nano-particles can be detected by detecting one or more proteins with a calcium binding domain. The calcifying nano-particles can be captured, identified, or both prior to, simultaneous with, or following detection of one or more of the proteins. Capture or identification of the calcifying nano-particle can indicate that the detected proteins are on the calcifying nano- particles. The calcifying nano-particles can be captured by binding at least one compound to one or more of the proteins, wherein the compound is or becomes immobilized. The calcifying nano-particles can be identified by binding at least one compound to one or more of the proteins, wherein the calcifying nano-particles are separated based on the compound. The calcifying nano-particles can be separated by fluorescence activated sorting. One or more of the proteins can be detected by binding at least one compound to the protein and detecting the bound compound. Detection of two or more bound compounds can indicate that the proteins to which the compounds are bound are on the calcifying nano-particle. The two or more compounds can be detected in the same location or at the same time. At least one of the compounds can be an antibody, wherein the antibody is specific for the protein. The calcifying nano-particles can comprise calcium phosphate and one or more of the proteins.
The proteins can be detected by detecting any combination of 10 or fewer of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor X/Xa, CD14, Prothrombin, Factor IX, Fetuin B, CD40,
Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin- 1, B2 microglobulin, CD 18, Laminin, Antitrypsin, Notch- 1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer, Factor V, gamma-Gla residues, TF-VIIa, Complement 3c3, Complement C4, Antichymotrypsin, Annexin V, Lipid A, Isopeptide bond, Vitronectin, Thrombin, Osteocalcin, Troponin T, Vimentin, Tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, Kallikrein 6, Prothrombin Fl , Antithrombin III, Thrombin, Factor VIII, Heparan Sulphate, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c-Jun, TGase3, alpha fetoprotein, Prostate Specific Antigen, erbB2, VEGF, alpha synuclein, Mucin- 1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Tgase 2, Ubiquitin, TLR 4, Cathepsin D, GFAP, RAGE, CD 9, Prostate Acid Phosphatase, Smith Antigen, PRGP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C Macrophage Scavenger Receptor Type I, Antithrombin, Protein S, BAFF on the calcifying nano-particle. The proteins can be detected by detecting any combination of 100 or fewer of the proteins. The proteins can be detected by detecting any combination of 5 or fewer of the proteins. The proteins can be detected by detecting any combination of 3 or fewer of the proteins. The combination of proteins can be detected in the same assay. The combination of proteins can be detected simultaneously. The combination of proteins can be detected on the same calcifying nano-particle. The combination of proteins can be detected on or within the same device.
The combination of proteins detected can constitute a pattern of proteins. The pattern can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination including but not limited to for example, heart or circulatory diseases such as Arteriosclerosis, Atherosclerosis, Coronary Heart Disease, Chronic Heart Failure, Valve Calcifications, Arterial Aneurysms, Calcific Aortic Stenosis, Transient Cerebral Ischemia, Stroke, Peripheral Vascular Disease, Monckeberg's Disease, Vascular Thrombosis; Dental Diseases such as Dental Plaque,
Gum Disease (dental pulp stones), calcification of the dentinal papilla, and Salivary Gland Stones; Chronic Infection Syndromes such as Chronic Fatigue Syndrome; Kidney and Bladder Stones, Gall Stones, Pancreas and Bowel Diseases such as Pancreatic Duct Stones, Crohn's Disease, Colitis Ulcerosa; Blood disorders; Adrenal Calcification; Liver Diseases such as Liver Cirrhosis and Liver Cysts; Testicular Microliths, Chronic
Calculous Prostatitis, Prostate Calcification, Calcification in Hemodialysis Patients, Malacoplakia; Autoimmune Diseases such as Lupus Erythematosous, Schleroderma, Dermatomyositis, Cutaneous polyarteritis, Panniculitis (Septal and Lobular), Antiphospholipid Syndrome, Arteritis Nodosa, Thrombocytopenia, Hemolytic Anemia, Myelitis, Livedo Reticularis, Chorea, Migraine, Junvenile Dermatomyositis, Graves Disease, Chronic Thyroiditis, Hypothyreoidism, Type 1 Diabetes Mellitis, Addison's Disease, and Hypopituitarism; Placental and Fetal Disorders, Polycystic Kidney Disease, Glomerulopathies; Eye Diseases such as Corneal Calcifications, Cataracts, Macular
Degeneration and Retinal Vasculature-derived Processes and other Retinal Degenerations; Retinal Nerve Degeneration, Retinitis, and Iritis; Ear Diseases such as Otosclerosis, Degeneration of Otoliths and Symptoms from the Vestibular Organ and Inner Ear (Vertigo and Tinnitus); Thyroglossal cysts, Thyroid Cysts, Ovarian Cysts; Cancer such as Meningiomas, Breast Cancer, Prostate Cancer, Thyroid Cancer, Serous Ovarian
Adenocarcinoma; Skin diseases such as Calcinosis Cutis, Skin Stones, Calciphylaxis, Psoriasis, Eczema, Lichen Ruber Planus or Lichen Simple Cysts;, Choroid Plexus Calcification, Neuronal Calcification, Calcification of the FaIx Cerebri, Calcification of the Intervertebral Cartilage or Disc, Mercranial or Cerebral Calcification, Rheumatoid Arthritis, Calcific Tenditis, Oseoarthritis, Fibromyalgia, Bone Spurs, Diffuse Interstitial Skeletal Hyperostosis, Intracranial Calcifications such as Degenerative Disease Processes and Dementia; Erythrocyte-Related Diseases involving Anemia, Intraerythrocytic Nanobacterial Infection and Splenci Calcifications; Chronic Obstructive Pulmonary Disease, Broncholiths, Bronchial Stones, Neuropathy, Calcifications and Encrustations of Implants, Mixed Calcified Biofilms, and Myelodegenerative Disorders such as Multiple Sclerosis, Lou Gehrig's, and Alzheimer's Disease. The pattern can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles. The pattern can identify the type of calcifying nano-particles detected.
The proteins can be detected by detecting the presence or absence of any combination of 10 or fewer of the proteins selected from the group consisting of proteins Bovine CaBP-HA complex, Fetuin A, Calmodulin, Tissue Transglutaminase II, MMP-9, MMP-3, CD 42b, NF-kappa B, Osteopontin, Factor X/Xa, CD14, Prothrombin, Factor IX, Fetuin B, CD40, Myeloperoxidase, Fibronectin, Factor VII, Tissue factor, Human complement 5b-9, Human CRP, Matrix GLA protein, CD61, Kappa Light Chain, Macrophage Ll Protein, Factor XIIIA, hsp 60, Fibrillin-1, B2 microglobulin, CD 18,
Laminin, Antitrypsin, Notch-1, BSA, LBP, PTX3, Complement C5, Fibrinogen, D-Dimer Factor V, gamma-Gla residues, TF-VIIa, Complement 3c3, Complement C4, Antichymotrypsin, Annexin V, Lipid A, Isopeptide bond, Vitronectin, Thrombin, Osteocalcin, Troponin T, Vimentin, Tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, Kallikrein 6, Prothrombin Fl, Antithrombin III, Thrombin, Factor VIII, Heparan Sulphate, Factor XI, c-jun, Fra-2, Fra-1, Jim B, P-c- Jun, TGase3, alpha fetoprotein, Prostate Specific Antigen, erbB2, VEGF, alpha synuclein, Mucin- 1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Tgase 2, Ubiquitin, TLR 4, Cathepsin D, GFAP, RAGE, CD 9, Prostate Acid Phosphatase, Smith Antigen, PRGP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C Macrophage Scavenger Receptor Type I, Antithrombin, Protein S, BAFF on the calcifying nano- particle. The pattern of the presence or absence of the proteins can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination. The pattern of the presence or absence of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles. The pattern of the presence or absence of the proteins can identify the type of calcifying nano- particles detected. The presence of one or more of the proteins can indicate or identify a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination. The presence of one or more of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles. The presence of one or more of the proteins can identify the type of calcifying nano-particles detected. The absence of one or more of the proteins indicates or identifies a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination. The absence of one or more of the proteins can indicate or identify a treatment to inhibit, remove or prevent the calcifying nano-particles. The absence of one or more of the proteins can identify the type of calcifying nano-particles detected.
The proteins can be detected using a microarray, coded beads, coated beads, flow cytometry, ELISA, mass spectrometry, fluorescence, chemiluminescence, spectrophotometry, chromatography, electrophoresis, or a combination.
The proteins on the calcifying nano-particle can be detected by (a) capturing the calcifying nano-particle, (b) binding a detection compound to one or more of the proteins, and (c) detecting the detection compound. The proteins on the calcifying nano-particle can be detected by (a) binding a detection compound to one or more of the proteins, (b) capturing the calcifying nano-particle, and (c) detecting the detection compound. The calcifying nano-particle can be captured by binding a capture compound to one or more of the proteins, where the capture compound is or becomes immobilized. The proteins to which capture compounds bind can mediate capture, where the detection compound can be bound to one of the proteins, where the calcifying nano-particle can be characterized by determining which proteins mediate capture of the calcifying nano-particle to which the detected detection compound is bound. The capture compound can be bound to one of the proteins, where the detection compounds detected can indicate which of the proteins is present on the calcifying nano-particle, where the calcifying nano-particle can be characterized by which proteins are present on the calcifying nano-particle.
The identified proteins can identify the type of calcifying nano-particle. The identified type of calcifying nano-particle can be related to or associated with a disease or condition. The identified proteins can identify a disease or condition with which calcifying nano-particles having the identified proteins are related or associated. The identified proteins can identify a disease or condition that is caused by calcifying nano- particles having the identified proteins. The identified proteins can identify a disease or condition in which calcifying nano-particles having the identified proteins are produced. Subjects in which pathological thrombosis can occur via apatite-mediated clotting are useful targets for the disclosed methods. Such subjects can include (1) Patients with vulnerable plaque rupture exposing atheroma calcification; (2) Patients undergoing angioplasty or heart-lung machine perfusion; (3) Patients with massive bone fractures or dislocated implants releasing potentially apatite particles; (4) Patients with implants, catheters, wires or stents subject to calcium encrustation; (5) Cancer patients with soft tissue calcification; and (6) Healthy or sick people with CNPs in their blood or positive calcification scores in arteries. Such people in the last category can be identified using the disclosed compositions and methods.
The composition can comprise a calcifying nano-particle and one or more compounds bound to two or more proteins on the calcifying nano-particle. The compound can comprise an antibody, wherein the antibody is specific for the protein. The compound can block the calcifying nano-particle.
Examples A. Example 1 In this example evidence is presented of host molecules involving two families of calcium binding Gla-proteins, calcification-defense system and clotting Gla-proteins, simultaneously binding to apatite surfaces and calcifying nano-particles. Thus, it was discovered that both Gla-systems participate in the body's calcification-defense by spatially blocking apatite surfaces. It was also realized that this creates a novel clotting mechanism. Thrombosis (the clotting of blood within an artery or vein) is a major cause of death and serious illness. Patients with circulatory, autoimmune and renal diseases, diabetes and cancers have abnormal ongoing coagulation often leading to thrombosis. However the principle clotting pathways, intrinsic and extrinsic, do not fully explain how or why thrombosis blocks blood vessels. It has been discovered that exposed calcium phosphate mineral surfaces (such as on calcifying nano-particles) simultaneously bind clotting and mineral-defense proteins creating a clotting mechanism that combines both intrinsic and extrinsic factors to the common factor X (FX) and prothrombin activation. This is the first direct proof of a link between calcification, which is widespread in disease, and pathological clotting. It was discovered that this novel physiological clotting mechanism can be activated when apatite is injected intravenously in vivo. A clotting test was developed to measure effects of various surfaces, including apatite and calcifying nano-particles (CNPs), on blood clotting in vitro. A multiplex surface antigen pattern test was also developed to demonstrate the pattern of clotting factors and their activators on the surface of CNPs isolated from human plasma and serum. This multiplex surface antigen pattern test is an example of the disclosed method for detecting calcifying nano- particles. The significance of this novel calcium mediated clotting mechanism is far- reaching since many diseases have a thrombotic component which may cause death. Clinical experience in cardiovascular medicine suggested that contact of blood with exposed calcified surface leads to thrombi (Halloran and Bekavac, Neuroimaging. 2004 Oct;14(4):385-7; Demer, Int. J. Epidemiol. 31, 737 (2002); Bini et al., Arterioscler. Tromb. Vase. Biol. 19, 1852 (1999); Lahey and Horton, Am J Kidney Dis. 40, 416 (2002)). Recent coronary artery calcification (CAC) scoring data supports that view, because positive CAC scores are a biomarker to predict future atherosclerotic thrombotic events, such as myocardial infarcts and strokes (Demer, Int. J. Epidemiol. 31, 737 (2002)). Many studies have also shown that patients with calcification-associated diseases such as atherosclerosis, kidney and autoimmune diseases, diabetes and cancer often have abnormal ongoing blood coagulation and thrombosis (Doherty et al., Endocrine Reviews 25, 629 (2004); Caine et al., Neoplasia 4, 465 (2002); Chambers and Laurent, Biochem.
Soc. Transact. 30, 194 (2002)). Yet, prior to the present discoveries, there was an absence of experimental studies that link calcification directly to thrombus formation. Current theories on blood clotting involve the binding of tissue factor to factor Vila to provide for an enzymatically active complex which then activates factors IX and X, leading to thrombin generation and clot formation (Banner et al., Nature 380, 41 (1996)). Injury that exposes tissue factor under the endothelium is the key activator resulting in production of factor Xa. Vitamin- K-dependent, gamma-carboxyglutamic acid (Gla)-containing domains of clotting proteins in this family are homologous and are responsible for phospholipid membrane association considered to be the substratum for clotting activation cascades (Nelsestuen, Trends Cardiovasc. Med. 9, 162 (1999)). Normal hemostasis results in platelet activation, aggregation and more thrombin generation (Dumas et al., Science 301, 222 (2003)) leading to a clot covering the damaged area. Clot growth is stopped by anticoagulation cascades activating inhibitors of clotting. Furthermore, factor Xa and thrombin are assumed to diffuse through the developing clot, filled with their specific inhibitors, to the surface of the growing clot. Formation of a large thrombus blocking a blood vessel is difficult to explain with this hypothesis, and has been experimentally shown to be insufficient (Hathcock and Nemerson, Blood 104, 123
(2004)). Therefore, other explanations have been sought, e.g. the existence of a small pool of circulating tissue factor, factor X, or thrombin, as microvesicles, has been proposed (Del Conde et al., Blood 106, 1604 (2005)).
Four clotting factors (Factor II, Factor VII, Factor IX, Factor X) acting as proteolytic executors of the clotting cascade are calcium-binding proteins also known to bind to apatite/calcium phosphate via their calcium binding GIa domains. The classical models imply that the Gla-domains undergo calcium dependent conformation changes before or concomitant with binding to phospholipid membrane. It was discovered that calcium phosphate surfaces serve the dual function as a suitable substratum (replacing phospholipid membrane) and as activators in normal and pathological blood clotting. The significance of this for human (patho)physiology is high because there are many situations where calcium phosphate minerals can have contact with blood/clotting factors: (1) Acutely during bone fracture, bone surgery, and dental surgery; (2) Artificially with the introduction of uncoated implants, fillers and apatite adjuvants; (3) Chronically with the growth of calcium phosphate deposits in atherosclerotic vessels, catastrophically with rupture of vulnerable plaque, and via cell death, exposing pathological calcification (e.g. Randall's plaque) and stones; (4) Hematologically with calcium phosphate macromolecular complexes with matrix Gla-protein and fetuin that were detected by Price in blood of animals suffering massive bone degradation (Price et al., J. Biol. Chem. 278, 22153 (2003))--Price (Price et al., J. Biol. Chem. 279, 1594 (2004)) showed that blood calcium phosphate macromolecular complexes lead to rapid arterial calcification in vivo; and (5) Systemically with calcifying nano-particles (CNPs), known until now as nanobacteria. CNPs have been found circulating in blood and implicated in pathological calcification (Kajander and Ciftcioglu, Proc. Natl. Acad. Sci. U S A. 95, 8274 (1998)). Although CNPs are controversial in their content and genetic characterization, critics and proponents alike agree that CNPs have a calcium phosphate mineral surface (Kajander and Ciftcioglu, Proc. Natl. Acad. Sci. U S A. 95, 8274 (1998); Cisar et al., Proc. Natl. Acad. Sci. U S A. 97, 11511 (2000); VaIi et al, Geochim. Cosmochim. Acta 65, 63 (2001); Miller et al., Am. J. Physiol. Heart Circ. Physiol. 287, Hl 115 (2004); Ciftcioglu et al., Kidney Int. 67, 483 (2005)). 1. Materials and Methods
L Preparation of Apatite and CNPs Hydroxyapatite was prepared according to Poser and Price (Poser and Price, J.
Biol. Chem. 254, 43 (1979)) using sterile solutions. Calcifying nano-particles (CNPs) were isolated from fetal bovine serum (FBS) obtained from several manufacturers (Seralab, UK; Gibco, Paisley, Scotland; HyClone, Logan, UT and Biological Industries, Israel) using methods described earlier (Kajander and Ciftcioglu, Proc. Natl. Acad. Sci. USA 95, 8274 (1998)). ii. Acute toxicity
Colloidal solutions of synthetic apatite (Poser and Price, J. Biol. Chem. 254, 43 (1979)) or CNPs in sterile phosphate buffered saline (PBS; 0.14M NaCl, 2.7 mM KCl, 8 mM Na2HPO4, 1.5 mM KH2HPO4, pH 7.4) were injected (at a dose of 0-50 μ\ wet pellet) into tail vein of Wistar rats. Rats were euthanized with phenobarbital 48 hours later and tissue samples were excised and placed to a fixative, 4 % paraformaldehyde, within 2 minutes from start of anesthesia. Tissues were processed to paraffin blocks, sectioned, deparaffmized and stained with H&E and with TUNEL assay for apoptotic changes with In situ Cell Death Detection Kit, AP (Roche) according to the manufacturer's instructions. Tissues were pretreated for TUNEL staining with 20 μg/ml proteinase K (Sigma, molecular biology grade) in 10 mM Tris/HCl, pH 7.4 for 15 min at room temperature. Apoptotic changes were evaluated with light microscopy. The method used detected apoptosis based on labeling of DNA strand-breaks using modified nucleotide labeling by terminal deoxynucleotidyl transferase visualized with enzymic reaction using Fast Red substrate (Roche). No changes were observed in control rats exposed to sterile PBS. The study was approved by the Ethics Committee of the University of Kuopio. iii. Thrombosis detection after i.v. injection of 99mTc-labeled apatite or CNPs in rabbits
Biodistribution study data on 99mTc-radiolabeled CNPs and apatite by Akerman et al. (Akerman et al., Proc. SPIE Int. Soc. Opt. Eng. 3111, 436 (1997)) was re-evaluated to detect thrombotic changes after i.v. injection. Dynamic imaging data (1 frame/minute) revealed thrombosis associated with radiolabeled material. Thrombus formation was observed in pulmonary artery on first pass through pulmonary circulation, and was Verified at autopsy at 48 hours. iv. Whole blood clotting slide test
Clotting induced by apatite was detected initially by using standard whole blood clotting time tube tests, with added glass beads, incubated at +37°C water bath with or without apatite. The clotting times were of the order of 2 minutes and did not allow precise evaluation of subtle changes by extraneous materials on clotting time due to need of sample preparation time, such as mixing the extraneous minerals. This could not be amended by using anti-coagulated blood samples (citrate or EDTA), reconstituted with 25 to 50 mM CaCl2 at start of the test, because such samples clotted poorly indicating irreversible interference by the anticoagulant to some important player(s) in clotting.
A novel test platform was developed using glass slides (Menzel-Glaser, Braunschweig, Germany) incubated at room temperature. The method allows for measuring changes in the clotting time induced by contact with foreign surfaces, i.e. plain glass or coated glass, and for studying the effects of drugs on the clotting induced by foreign surface. Glass slides were coated with synthetic apatite (Poser and Price, J. Biol. Chem. 254, 43 (1979)) and controlled by TEM and EDX analysis (Kajander and giftcioglu, Proc. Natl. Acad. Sci. USA 95, 8274 (1998)). 250 μ\ of apatite colloidal suspension (10% pellet containing suspension) was pipetted to each slide, and slides were dried +37°C overnight. Commercial heat-fixed CNP-coated slides were obtained from Nanobac Oy, Kuopio, Finland. Plain glass slides without further processing were used as a foreign surface. Effect of Calcium EDTA, disodium EDTA, and clodronate on blood clotting time was investigated by adding 10 μl solution to a plain glass slide immediately before addition of blood. Calcium EDTA and disodium EDTA were from Fluka. Clodronate was a gift from Professor Jouko Vepsalainen (University of Kuopio).
Venous blood was collected with venipuncture from 19 random volunteers participating in CNP epidemiological study (Ethical Committee Approval, Kuopio University). Volunteers signed an informed consent. Blood was collected with venipuncture in siliconized glass serum tubes, EDTA plasma tubes or citrate plasma tubes (Terumo), and was tested immediately after collection for whole blood clotting time on different test platforms.
200 μl of freshly drawn blood was added to pre-coated or plain glass slides which were put on a tilting shaker 15 tilts/minute at room temperature until formation of a solid clot was observed as "frozen droplet". Experiments were carried out usually in triplicate to determine reproducibility of tests. CV% for the triplicate tests were less than 6.81% (CNP-coated slide, n = 13), 8.79% (apatite-coated slide, n = 15) and 10.37% (non-treated control slide, n = 15). Clotting time results were analyzed by Bonferroni (Dunn) t Test (Table 1). v. Proteomics on proteins bound to apatite particles Protein-free apatite particles in DMEM (Gibco) without any additives were suspended into 10% FBS-DMEM and were immediately centrifuged at 14 000 rpm, 30 rain at +4°C. The pellet was washed two times by suspending with sterile PBS followed by centrifugation at 13,200 rpm, 20 min at room temperature. Pellet was frozen prior to analysis. Proteomics analysis was provided by Protana, Montreal, Canada. The SDS- boiled samples were subjected to ID SDS-PAGE under reducing conditions. Protein bands were detected by Coomassie staining, excised and processed following standard procedures including: 1. The proteins in the gel plug were reduced with DTT.
2. The free cysteine residues were alkylated with iodoacetamide.
3. The proteins were digested with the endoprotease trypsin.
4. The peptides produced were extracted in neutral, acidic and basic conditions. vi. Mass Spectrometry Analysis The peptide mixtures were separated by C 18 reverse phase chromatography into a
Thermo-Finnigan LTQ-FT ion trap/FTICR hybrid mass spectrometer coupled with a nano- spray interface. The mass spectrometer was operated in data-dependent mode to obtain tandem (ms/ms) spectra of each peptide above an intensity threshold as it emerged from the chromatography column. The raw data files were processed using LCQ-DTA to generate peak lists of the tandem spectra. The processed data was searched with Mascot (Matrix Sciences, London UK) using the NCBI non-redundant database. The Mascot results were curated by mass spectrometry scientists to correlate the results with the raw data (Table 2). vii. Nanocapture and SAPIA ELISA Methods
Presence of CNPs was first detected with commercially available Nanocapture ELISA kit (Nanobac Oy). The test measures presence of CNPs in human serum or plasma, with a measurement range from 0 to 640 units (Pretorius et al., HIV Med. 5, 391 (2004)). The capture kit uses separate step-wise capture and detection reactions involving two monoclonal antibodies targeted on different surface epitopes on the CNPs.
Surface Antigen Pattern Immunoassay (SAPIA) test was developed to detect presence of multiple proteins on CNPs (Figures 1 A-IE). The SAPIA test here used specific commercial antibodies against designated targets (Table 3), in this case against clotting and anti-calcification Gla-proteins (Figure IA). SAPIA method was first tested using plasma and serum samples from 8 persons. Human plasma and serum samples were first tested to determine if they are comparable samples (Figure 2). Note that the results of positive sample shown are exceptionally high for clotting factors (Figure 2A). Based on the results obtained with these 8 samples, both serum and plasma samples could be used to test the specified parameters. Thereafter, a random panel (n = 16, each sample was combined from 1-5 human serum samples of similar CNP unit values to make up the necessary volume needed to run many tests, done in duplicate) with Nanocapture results ranging from 0-640 Units was selected for the SAPIA test.
SAPIA plates were made by coating high binding polystyrene ELISA plates (Coming, USA) with antibodies against anti-calcification proteins and GIa clotting factors and control antibodies. SAPIA was controlled by using antibodies against human serum albumin, D-Dimer, NF-κB and fibronectin as these proteins were not expected to be specifically bound on particle surface (Figure IA). Monoclonal antibodies were diluted at a final concentration of 1 μg/ml with IX PBS, pH 7.4, 100 μl/well to ELISA plates and incubated at +4°C overnight. Polyclonal antibodies were diluted to a concentration of 10 μg/ml and plates were coated as above. After coating procedure, plates were washed once with TBS-Tween 20 and blocked by adding TBS-Tween 20 300 μl/well and incubated 2 hours at room temperature. Thereafter, blocking solution was removed and storage solution 0.05% NaN3-TBS was added 200 μl/well, and the plates were stored sealed with tape in a refrigerator.
Before use, storage solution was removed and plates were washed once with TBS- Tween. 50 μl/well of Assay Buffer (0.05 M Tris, 0.15 M NaCl, 0,05% Proclin 300, pH 7.5 with 1% mouse serum) was added in duplicates and 50 μl/well serum sample was added (Figure IB). Plate was sealed with tape and incubated 1 hour at room temperature with moderate shaking (Figure 1C). Plates were washed four times using TBS-T ween and detection antibody HRP-8D10 (Nanobac Oy) was added 100 μl/well. Plates were incubated 1 hour at room temperature with moderate shaking (Figure ID). Plates were washed four times using TBS-T ween and TMB substrate (Moss Inc., Pasadena, MD
21123) was added 100 μl/well. Plates were sealed and protected from light with foil and incubated 20 min at room temperature with moderate shaking (Figure IE). Absorbance at 630 nm was read with microplate reader (Biohit BP 808). Blank values were subtracted and unit values were calculated from standard curve of Nanocapture ELISA test using TableCurve 2D program (Systat, Point Richmond, CA). Pearson Correlation Coefficients (N=I 6, Prob > |r| under HO: Rho=0) were calculated (Tables 4 and 5). Anti-calcification proteins and coagulation GIa factors were found to be present in CNPs (Figures 3 and 4). viii. Activation of prothrombin by apatite in vitro Human prothrombin >95 % pure (Calbiochem) and two samples of bovine prothrombin >98 % pure (ICN, Aurora, OH and American Diagnostica, Stamford, CT) were diluted to a concentration of 10 μg/ml, 1 μg/ml and 0.1 μg/ml in 25 niM Tris, 150 mM NaCl and 5 mM CaCl2, pH 7.4 (which is the substrate buffer for thrombin). 20 μl of prothrombin solution was mixed with 20 μl apatite (Poser and Price, J. Biol. Chem. 254, 43 (1979)) and incubated 30 minutes with moderate shaking at room temperature. As control reactions, prothrombins at above mentioned concentrations were incubated with buffer only. Thereafter, thrombin substrate Sar-Pro-Arg-pNA (Bachem, Bubendorf, Switzerland) 0.5 mg/ml (in substrate buffer solution, first solubilized in acetone) was added (100 μl) to all wells and plate was transferred to +37°C. Reaction was monitored with Elisa reader at 405 nm. Control absorbances were subtracted to produce data shown in Figure 5. No thrombin generation was found to take place in prothrombin wells without hydroxyapatite addition. ix. Thrombin and FXa activity measurements from SAPIA tests
Serum and plasma samples from 6 healthy volunteers were used for measurement of thrombin and FXa activity in particles captured with SAPIA using plates coated with antibodies against CNPs, thrombin and Factor XJXa. 50 μl of serum or plasma samples were pipetted onto plates and 50 μl of Assay Buffer (0.05 M Tris, 0.15 M NaCl, 0,05% Proclin 300, pH 7.5 with 1% mouse serum) was added. Plates were incubated 1 hour at room temperature with moderate shaking. Plates were washed 4 times, before 100 μl specific substrate was added. Three substrates were used for thrombin: Bx-Phe-Val-Arg- pNA HCl (Bachem), Sar-Pro-Arg-pNA (Bachem) and /33-Ala-Gly-Arg-pNA-acetate (Sigma, St. Louis, MI). One substrate was used for Factor Xa, CH3 -D-CHA-GIy- Arg- pNA-AcOH (Sigma). Thrombin substrates Bx-Phe-Val-Arg-pNA HCl (0.136 mg/ml) and Sar-Pro-Arg-pNA (0.25 mg/ml) were in 25 mM Tris, 150 mM NaCl, 5 mM CaCI2, pH 7.4; and /3-Ala-Gly-Arg-pNA-acetate (1 mM) in 50 mM Tris, 100 mM NaCl, 5 mM CaCl2, pH 7.4. Factor Xa substrate was CH3 -D-CHA-Gly-Arg-pNA-AcOH (0.5 mM) in 50 mM Tris, 100 mM NaCl, 5 mM CaCl2, pH 7.4. Plates were sealed with tape and parafϊlm to avoid evaporation and incubated at +37°C. Absorbance was measured at 405 nm using Microplate Reader (BP-808, Biohit). Measured sample values were compared to a standard curve made using thrombin from Terumo. Only thrombin substrate Sar-Pro- Arg-pNA gave weak positive results with serum samples after 18 hours incubation. The results did not correlate with the presence of CNPs, based upon Capture ELISA results.
Thrombin substrates Bx-Phe-Val-Arg-pNA HCl and /3-Ala-Gly-Arg-pNA-acetate failed to give positive signals. Factor Xa substrate CH3 -D-CHA-GIy- Arg-pNA- AcOH gave weak positive results for serum samples after 18 hours incubation. Results did not correlate with the presence of CNPs. Thus, the results indicate only non-specific binding of thrombin and Factor Xa activity to ELISA plate which was present only in serum samples.
Therefore, the CNP-bound antigens must have been in an inactive form, as is expected in blood samples of healthy people. x. Immunohistochemical staining for antigen pattern analysis Paraffin-embedded arterial tissue blocks representing various forms of severe atherosclerotic lesions were obtained from commercial sources (Clinomics BioSciences, Inc., Pittsfield MA 01201. Tissue samples were collected from New York area and processed under Institutional Review Board permit). Thin sections were cut using standard techniques. Sections were deparaffinized without decalcification and stained with monoclonal antibodies for antigen pattern analysis mapping calcification defense proteins, clotting factors and CNPs. The staining protocol was tailored for each antibody,
TM see Table 3. Power Vision+ PoIy-HRP IHC kit (Irnrnuno Vision Technologies, Brisbane CA 94005) was used according to manufacturer's instructions. Color was developed using 3,3'-diaminobenzidine substrate. Sections were counterstained using Mayer's
Hematoxylin (Reagena, Siiilinjarvi, Finland), mounted and staining results were evaluated with light microscopy. Calcium deposits were stained with von Kossa staining. Dehydrated slides were immersed into 5% silver nitrate (BDH) solution for 1 hour under IOOW lamp. Slides were rinsed shortly with distilled water and further immersed into 5% sodium thiosulphate (Merck) for 2 minutes. Slides were washed three times with distilled water before staining with Kernetchrot solution (Reagena) for 5 minutes. Slides were rinsed with distilled water, dehydrated and mounted with Depex (BDH). Samples were microscoped with Nikon FXA microscope. Antigen patterns in soft plaque and hard plaque were compared. A specific pattern was observed that involved strongest intensity of staining in calcifications, followed by focal necrotic areas, and individual areas in media and intima layers. The pattern was comparable for all studied GIa protein antigens and CNPs. Patterns of Factor XIIIA and tissue factor showed a more universal presence, albeit also indicated accumulations of these antigens in the atherosclerotic lesions. Stainings carried out omitting primary antibody were negative. Calcification staining with von Kossa method matched with large macroscopic calcifications and some of the microscopic areas where CNP and GIa protein stainings revealed positivity. This can be interpreted to mean that although the tissue staining pattern was comparable, the sensitivity of von Kossa staining is inferior to immunostainings in detecting CNPs and nanoscopic calcifications. 2. Results
This example various forms of apatite were studied, including inorganic synthetic (Poser and Price, J. Biol. Chem. 254, 43 (1979)) and organic form built on calcifying nano-particles, referred to previously as nanobacteria (Kajander and Ciftcioglu, Proc. Natl. Acad. Sci. USA 95, 8274 (1998)). Hydroxyapatite formation includes several metastable calcium phosphate intermediate phases (NancoUas, Pure & Appl. Chem,l 1, 1673 (1992)). Brushite (dicalcium phosphate dihydrate) and octacalcium phosphate are considered initial phases that are transformed to hydroxyapatite, which is the most insoluble calcium phosphate mineral phase forming under neutral or basic conditions (Johnsson and Nancollas, Crit. Rev. Oral, Biol. Med. 3, 61 (1992)). Basic calcium phosphate (BCP) is a term that includes various calcium phosphate minerals, i.e. hydroxyapatite, carbonate- apatite, octacalcium phosphate and brushite. hi this example the general name apatite is used for the calcium phosphate mineral. Synthetic colloidal apatite was used as a control while performing acute toxicity studies for calcifying nano-particles (CNPs). Surprisingly, it was found that both iv injected apatite and CNPs caused ischemia-type tissue damage in the kidneys of rats. The pathognomic feature in ischemia-reperfusion kidney damage is that glomeruli are saved whereas tubuli die (Park et al., Am. J. Physiol. Renal Physiol. 282, F352 (2002)). The kidney damage was dose-dependent, and did not occur when two microliter or less apatite was injected. Control animals receiving only phosphate buffered saline (PBS) did not show histological changes in kidneys. There were also signs of thrombotic events in large blood vessels and cardiac chamber walls.
99m
To verify thrombotic events after iv injection, bio-distribution of Tc-labeled colloidal apatite and CNPs was reexamined by using Single Photon Emission Computed Tomography (SPECT) after iv-injection in rabbits (Akerman et al., Proc SPIE Int Soc Opt Eng 3111, 436 (1997)). Thrombosis was observed in left pulmonary artery starting within one minute of the injection and was stable and could still be detected 48 h after injection. i. How was thrombosis activated? Standard blood coagulation tests (e.g., activated partial thromboplastin time, prothrombin time) were inappropriate to measure calcium phosphate mineral surface- mediated clotting because those tests require use of anticoagulants, which would interact with an apatite surface. Counteracting the anticoagulants with high calcium chloride concentrations, as is required in the tests, creates non-physiological competition for binding between free calcium (tens of times higher than the physiological) and calcium phosphate surface. Furthermore, the apatite surface would be modified by a solution high in calcium, forming other forms of calcium minerals on the surface (e.g., octacalcium phosphate) (Boskey, J. Phys. Chem. 93, 1628 (1989)). Apatite is stable under physiological calcium and phosphate concentrations. Therefore, to study the effects of apatite on clotting, a whole blood clotting slide test was developed. In this test, plain objective glass, or objective glass coated with various forms of apatite, or test drugs, were used as test platforms. 200 μL of freshly collected human blood was applied on the slides, which were tilted ±30°, 15 tilts per minute, at room temperature. Clotting time was established at the time when droplet contents stopped moving. The test indicated that clotting was two times faster on apatite coating compared to the control slide. CNP coating also decreased clotting time significantly (Figure 6; Table 1). The method was controlled by using EDTA or citrate plasma samples, which never clotted, even when exposed to apatite coated test platforms. Calcium EDTA and a small concentration of the calcium binding drug etidronate did not affect the clotting time. Therefore the test appropriately measured clotting triggered by a foreign surface, glass. It was surprising that the apatite surface was superior at inducing clotting over the untreated glass, the traditionally used foreign surface in clotting tests. ii. How does apatite cause clotting?
Calcium is a major player throughout the clotting process. The extrinsic clotting pathway is activated by tissue factor, which is a 40 kD membrane-spanning protein expressed normally by almost all cells, except the endothelium. Endothelial damage exposes tissue factor, which binds and allosterically activates a serine protease, factor Vila (FVIIa), in the presence of calcium. This complex then proteolytically activates two serine protease zymogens, factor IX (FIX) and factor X (FX) (Banner et al, Nature 380, 41 (1996)), again in the presence of calcium, resulting in formation of factor Xa (FXa), which splits prothrombin to thrombin, again in the presence of calcium, which is the final coagulation executor proteolytically insolublizing fibrinogen as fibrin. The clot is further stabilized by cross-linking by factor XIIIa (FXIIIa) (activated by thrombin in the presence of calcium). The intrinsic pathway commences upon exposure to a foreign negatively charged surface, activating calcium-dependent conformational changes of clotting factors resulting in binding to a platelet or other phospholipid membrane, and leading to an activation-amplification cascade which eventually activates FX resulting in thrombin release.
Proteomics analysis revealed prothrombinase complex on apatite surface together with players of complement, antibodies and protease inhibitors. Although the use of serum to test clotting factors is not preferred, this proved the ability of apatite surface to bind clotting factors and provided information about what proteins can bind in biological situations, for instance on CNPs.
The same proteomics method was not preferred for CNPs because 1-D or 2 -D electrophoresis can not be run without extracting proteins from the particles, which is difficult. Difficulty in extracting proteins form CNPs indicates that the proteins on CNPs are cross-linked. Therefore, the surface protein patterns of CNPs were mapped using Surface Antigen Pattern Immuno- Assay (SAPIA; Figure 1), which is an example of a specific embodiment of the disclosed method of detecting proteins on calcifying nano- particles. In this technique specific antibodies directed against clotting and anti- mineralization proteins were used (the 5/2 capture antibody from the Nanocapture Elisa kit can be used to form the standard curve for any of the assays. The results can be used for calculation of algorithims for specificy disease diagnosis). SAPIA profiles of CNPs using plasma and serum samples were practically identical (Figure 3). These results indicated that serum samples can be used for the test. The results also indicated that particles with this specific antigen surface pattern can be isolated from human blood without any culturing steps. SAPIA results were stable after freeze-thawing, detergent (Tween20), EDTA or citrate application. Evidence was found that the detected proteins are cross- linked (very little protein released by SDS boiling). The stability of CNPs makes them amenable to surface antigen mapping with SAPIA technique which involves extended step-wise incubations separated by numerous washings before the detection. This feature of CNPs also allows the use of harsh treatments, when useful or desired, in other assays and detection methods.
SAPIA indicated that clotting factors V, VII, IX, X, tissue factor-FVIIa complex, fibrin, fibrinogen, FXIIIa, fragments of factor II, thrombin and prothrombin Fragment 1, but not prothrombin Fragment 2 are on CNPs (Tables 2 and 3; Figure 2). Both matrix
GLA-protein and osteocalcin were present on CNPs as well. The pattern of these factors was positively correlated with results using the Nanocapture kit with a high confidence level, indicating that the particles are composed of these surface antigens. SAPIA did not give positive results with capture antibodies specific for fibronectin (Figure 3) nor for human serum albumin, D-Dimer or NF-kB. The results prove that the particle surface contains players of the intrinsic and the extrinsic pathway (Table 2). Much of the CNP prothrombin has been activated to release thrombin and prothrombin Fragment 1. Prothrombin fragment 1 has 10 GIa residues whereas fragment 2 has none, which can explain why fragment 2 is released. However, it was surprising that the thrombin is retained in the particle. There may be mechanism(s) to retain it, such as crosslinking, or complex formation. For example, thrombin is known to make a complex with FXIII and fibrin (Aliens et al., Blood 100, 743 (2002)), which were also found on the particle. It was discovered that apatite binds clotting factors and their activators, concentrating them in close proximity, thus providing the necessary players for clotting on a suitable substratum (Figures 7-9). GIa residues in the GIa domain are known to bind to apatite. Free blood calcium completes the activation by binding to the rest of Gla-residues (Figure 8). Interaction of prothrombin with hydroxyapatite mineral has been shown by Romberg (Romberg et al., Arterioscler. Thromb. Vase. Biol. 18, 33 (1998)) to be comparable to anti-mineralization Gla-proteins. The clotting cascade has Gla-containing factors II, VII, IX, and X, and their levels have been linked to hypercoagulability and as risk factors for atherosclerosis and its thrombotic complications (Xu et al., Arterioscler. Thromb. Vase. Biol. 18, 33 (1998); Carlsson et al., Eur. J. Biochem 270, 2576 (2003)). Calcium phosphate, the key element in apatite, is a normal body constituent, therefore cannot be regarded as foreign surface that activates the intrinsic pathway of clotting. The key player in the extrinsic pathway, tissue factor, is not a calcium binding protein but might act as a player on the apatite after complex with FVIIa (Table 2; Figure 7). To find out whether particle-bound thrombin was active, chromogenic thrombin substrate incubations were made after capture of the CNPs. Very slight conversion of thrombin substrate was observed after 3 hours incubation at 20°C in the most positive samples, but this could have been due to other proteolytic activity on CNPs. Therefore, most if not all of particle immunologically detected thrombin must have been inactive, as was expected, because active thrombin would otherwise lead to dire consequences. The body has an efficient anti-thrombin system to inactivate the thrombin. SAPIA for detecting Anti-thrombin III gave only 2/16 high positive results (for the samples with the highest Nanocapture results). The test may have failed to detect less positive cases due to the use of an antibody that binds to an epitope known to block the thrombin-anti-thrombin complex formation, which means that its epitope was inside the inactive complex. Factor Xa activity chromogenic substrate test revealed no activity. This factor is also inactivated by anti-thrombin.
It was also tested whether non-enzymatic activation of thrombin could take place on apatite. The results presented in this example indicate that a tiny amount of thrombin activity, measurable with the chromogenic substrate, was generated on the apatite but not on the ELISA plate surface exposed with purified human or bovine prothrombin.
Using SAPIA, matrix Gla-protein and osteocalcin were identified on the CNPs. The presence of calcification-defense GIa proteins and blood clotting factors of the extrinsic and intrinsic pathways were identified on the same particle. To def ermine if the two classes of GIa proteins could be associated with calcification in atherosclerotic lesions in humans, immunohistochemical stainings on human atherosclerotic lesions were made. Immunohistochemical staining showed CNPs were concentrated in both soft plaque and overt calcifications or hard plaque areas. The same type of localization was found for several members of both GIa protein families. It is noteworthy that von Kossa staining could detect only large calcific areas whereas the CNPs were found as almost nanoscopic calcifications. 3. Discussion The results in this example show that apatite surfaces lead to rapid activation of the clotting cascade. Among other implications, this provides support for long-established clinical evidence suggesting that calcified lesions participate in formation of atherothrombi. It was proven that apatite surfaces simultaneously bind multiple GIa proteins, some of which are clotting proteins. This creates a platform for a clotting mechanism that combines both intrinsic and extrinsic factors to the common FX and prothrombin activation. This clotting mechanism is shown in Figures 7-9. The diagram depicts a novel platform, formation of complexes and activation of a clotting cascade on apatite surfaces. It was also shown that apatite itself can contribute to conformational changes leading to activation of prothrombin on apatite surfaces to release active thrombin. This non-enzymatic activation was much less rapid without the added clotting cascade players, yet proves the essential role that apatite plays. Prothrombin activation involves initial reactions with calcium, followed by a membrane prothrombinase complex formation leading to a thrombin release (Borowski et al, J. Biol. Chem. 261, 14969 (1986)). The players in this complex and their activators were shown in this example to be bound on apatite surfaces. It was also shown that the apatite-mediated clotting was twice as fast as clotting mediated by contact with a foreign surface, in this case glass, activating the intrinsic pathway.
The apatite-mediated clotting cascade, as with other clotting cascades, would have to be meticulously controlled by anti-thrombin, Protein S and C, heparin and other anti- clotting mechanisms and fibrinolytic systems to maintain a fine balance between activation and inhibition. Tissue factor found on CNPs shows that apatite particles can activate clotting using extrinsic pathway players. This process could be controlled by inhibitors, for example, by tissue factor inhibitor pathway (TFIP), which is likely since CNPs were not more active than apatite, which lacked the presence of the tissue factor. However, for the reasons shown above, processes required to control apatite-mediated clotting break down, leading to massive thrombosis.
This example shows for two forms of apatite that sudden circulatory exposure leads to thrombotic events, indicating that exposure of blood to apatite can have catastrophic results. Thrombosis was found when blood in a vessel was suddenly exposed to apatite pellet (colloidal) volume in excess of two microliters. Apatite exposure of this magnitude could take place as a consequence of, for example, bone fracture, rapture of vulnerable plaque revealing pathological vascular calcification, or in any situation where circulatory apatite particle counts would become locally high, for example, after rapture of a cyst filled with them.
Apatite-mediated clotting can have an important physiological function in bone physiology. Large bones have cancellous surface compartments with a diameter larger than largest blood vessels. Thus bone fracture often leads to clots up to 10 centimeters in diameter that must be made relatively rapidly to prevent the victim from bleeding to death. Exposed apatite could serve as the platform, providing booster power for clotting, since the hollow bone cannot reduce its diameter as damaged blood vessels do via vasoconstriction, and the bone has few tissue factor sources. Bone trabeculae are covered with only a monocellular layer, endostium, and the cortical bone has very low cell density (no subendothelial cells available with cell tissue factor carrying membranes as present in other tissues). It had not been clear how tissue factor-mediated clotting could take place in bone, but based on the results in this example it can be seen that the exposed bone could allow apatite-mediated clotting. Intriguingly, bone contains significant amounts of clotting GIa proteins. Those proteins are present at 1 - 2 % level of the non-collagen proteins in bone They could act with the bone Gla-protein osteocalcin, which was also found on CNPs, to control bone mineralization and/or provide protection against bleeding after bone fracture, where large areas of calcified surface are exposed. Gla-proteins are also found in kidney stones, suggesting a role in stone formation via both mineralization and thrombin production via thrombotic events or other mechanisms. Prothrombin Fl is the most common protein associated with kidney stones, and thrombin has been detected in urine in kidney diseases. Thrombogenic mechanisms have been proposed for kidney stone formation (Stoller et al., J. Urol. 171, 1920 (2004)). There is a very high incidence of calcifying nano-particles in disease processes known to be associated with calcification/thrombosis, for example, 97.5% associated with carotid stenosis, whereas only 10% association in Crohn's disease. Furthermore, the faster whole blood clotting time observed with calcium phosphate (bio)films supports the hypothesis from cardiology that rupture of unstable plaque endothelium exposing calcific plaque can cause clotting and lead to thrombosis and myocardial infarction or stroke. CNPs were shown to be present in atherosclerotic calcification and in soft plaque as nanoscopic calcific particles. This is consistent with a pathological role for any sized calcification in the vasculature. Calcification can be the driving force for atherothrombosis. The connection between apatite particles in the wrong part(s) of the body and inflammation and immunological activation has been shown (Morgan et al., Arthritis Rheum. 50, 1642 (2004); Nadra et al., Circ. Res. 96, 1248 (2005)).
Immunohistochemical stainings revealed the accumulation of clotting and anti- mineralization Gla-proteins on the CNPs. This evidence directly shows that GIa proteins have particular accumulations in atherosclerotic lesions associated with calcifications of all sizes. Thus, calcification is linked to both clotting factors and anti-mineralization Gla- proteins. Both clotting factors and anti-mineralization Gla-proteins have been separately shown to co-localize with calcification in atheromas and similar types of lesions (Bini et al., Arterioscler. Tromb. Vase. Biol. 19, 1852 (1999); Mullins et al., FASEB J. 14, 835 (2000); McKee Nature, but not in the same lesions prior to the results in this example.
Since CNPs are detectable just below the endothelium, they can contribute to thrombotic clotting together with the circulating CNPs when the endothelium lining is damaged. The results in this example indicate a role for an apatite-mediated clotting system in thrombotic events. Studies on thrombogenicity of biomaterials have examined heparin stabilized apatite, or heparinized animals. Since heparin is an anticoagulant, such studies do not reveal thrombotic potential adequately. Thus, biocompatible materials may not be hemocompatible. Apatite coated implants are widely used due to their bone biocompatibility. Many new medical applications for apatite have been proposed including drug delivery systems to blood, lung airways, or tissue; as a vaccine adjuvant; a vehicle for DNA transfer; and even as stent material for blood vessels. However, the effects of implants or injected apatite outside of bone and teeth have not been widely studied. Biocompatibility studies for calcium phosphate mineral particles or surfaces do nox seem to nave reported thrombotic events. Aoki et al reported vascular collapse as the cause of death in rats injected i.v. with colloidal apatite. Although Aoki reported severe hypoxia and elevation of infarct enzymes, above a threshold dose, the intravenous administration to humans was suggested to be feasible while using dosage less than LD50 for rats (Aoki et al., J. Mater. Sci. Mater. Med. 11, 67 (2000)). However, thrombi in rats injected with apatite i.v. were observed as descrubed in this example. Therefore, the biocompatibility of apatite, when exposed to circulation, is now seriously in question. This does not suggest that apatite use in implants should be discontinued, but rather that it must be separated from the blood in biocompatible ways with, for example resilient coatings, just as the body separates natural bone from blood via endostium. Thus, disclosed herein are compositions comprising apatite and a coating material, where, for example, the coating material limits exposure of the blood of a subject when the composition is in a subject.
The contrast between results in this example and apatite biocompatibility published earlier may be due to the ISO 10993-4. It requires the use of citrate or hirudin blood, or plasma and allows their application on implant materials while performing hemocompatibility testing (Seyfert et al., Biomolecular Engineering 19, 91 (2002)). The results in this example indicate that ISO 10993-4 required conditions cannot be used to detect blood clotting on apatite. The following improvements in biomaterial testing were devised: (1) Complementing ISO 10993-4 with tests for whole blood clotting in the absence of anticoagulants; and (2) Stents, catheters and materials exposed to circulation should repel calcific biofϊlm formation, because calcifying particles have been found to bind and coat such surfaces (Kajander et al., NASA/CP-2002-210786, 51 (2002)). Thus, disclosed herein is a method of testing biocompatibility comprising testing blood coagulation in the absence of anticoagulants and a method of testing materials that will be exposed to circulating blood for formation of calcific biofilm formation. Subjects in which pathological thrombosis can occur via apatite-mediated clotting are useful targets for these and other method disclosed herein. Such subject include (1) Patients with vulnerable plaque rupture exposing atheroma calcification; (2) Patients undergoing angioplasty or heart-lung machine perfusion; (3) Patients with massive bone fractures or dislocated implants releasing potentially apatite particles; (4) Patients with implants, catheters, wires or stents subject to calcium encrustation; (5) Cancer patients with soft tissue calcification; and (6) Healthy or sick people with CNPs in their blood or positive calcification scores in arteries. Such people in the last category can be identified using the disclosed compositions and methods.
This example describes a newly discovered pathophysiological mechanism linking pathological calcification to thrombosis. Blood anti-calcification Gla-proteins and GIa- clotting factor proteins were shown to bind to calcium phosphate surfaces creating a novel clotting mechanism capable of causing thrombosis where blood is in contact with apatite or CNPs. This was shown by detecting thrombosis after IV injections of apatite and CNPs in vivo in rats and rabbits, leading to thrombotic events, including ischemia- reperfusion damage. A whole blood coagulation slide test was developed to measure effects of various surfaces, including apatite and CNP, on blood clotting in vitro. Avid binding of Gla-clotting factors to apatite was detected by proteomics. A novel SAPIA test was developed to demonstrate the pattern of clotting factors and their activators on the surface of CNPs isolated from human plasma or serum. The apatite prothrombin interaction resulted in a small amount of thrombin activity detected by chromogenic substrate, despite the absence of other clotting factors. B. Example 2
The SAPIA method described in Example 1 was utilized to detect CNP components in 16 serum samples. Tables 11 and 12 illustrate the results of SAPIA testing. Table 11 shows raw absorbance data in the upper half of the table for 97 proteins and components measured in 16 human serum pools. The lower half illustrates units per ml. The pools were obtained by mixing the serum from 1-5 donors for each pool, pooled according to capture ELISA results that showed similar antigen levels.
The results show, with few exceptions, that each protein or component was detected on CNPs. Significant patterns are realized via intpretation of the data. Observations showed that certain proteins and/or components exhibit high and low values. Trends were realized and, for example in Table 11, different patterns are shown by anti- thrombin and anti-osteocalcin. At least 6-12 patterns are able to be visualized (qualitatively) by those skilled in the art.
Table 12 shows the statistical analysis as generated from the raw data of Table 11. The table shows correlation between the markers (100x100). Correlation coefficients greater than 0.5 indicate positive correlation (with low p values) and those values approaching 0.0 indicate a negative correlation. Therefore, statistical review via the generation of, for example, of box plots or scatter plots enables one skilled in the art to visualize data patterns that may be useful in the assessment, diagnosis, and therapeutic selection for certain diseases and/or conditions. Various algorithmic methods may be applied, for example, by multiplying, dividing, addition, or subtraction for various antigen values. These algorithms may be used in the diagnosis of diseases and/or conditions. Data may be further analyzed via more sophisticated techniques, for instance, cluster analysis, neural network, or multivariate loigistic regression techniques.
Cluster analysis is a multivariate statistical technique which assesses the similarities between units or assemblages, based on the occurrence or non-occurrence of specific artifact types or other components within them. Neural networks are a well-established technology for solving prediction and classification problems, using training and testing data to build a model. The data involves historical data sets containing input variables, or data fields, which correspond to an output. The network uses the training data to "learn" the solution to the problem by example. Since the network learns in this way, no complex models need to be created. Also, it is not necessary for your data to be complete or show a clear trend - neural networks can still converge to a solution under these conditions.
Logistic regression is part of a category of statistical models called generalized linear models. This broad class of models includes ordinary regression and ANOVA, as well as multivariate statistics such as ANCOVA and loglinear regression. An excellent treatment of generalized linear models is presented in Agresti (1996).
Logistic regression allows one to predict a discrete outcome, such as group membership, from a set of variables that maybe continuous, discrete, dichotomous, or a mix of any of these. Generally, the dependent or response variable is dichotomous, such as presence/absence or success/failure. Discriminant analysis is also used to predict group membership with only two groups. However, discriminant analysis can only be used with continuous independent variables. Thus, in instances where the independent variables are a categorical, or a mix of continuous and categorical, logistic regression is preferred.
These selected markers (biomarkers) are well known in the art to be indicative of or risk factors for disease. C. Example 3
Disease specific sera was obtained from Clinomics Bioscience Inc. for 15 diseases, n=40 per disease. Nano capture results are shown in Figures 11 and 13. The data indicated that CNPs were detectable in each disease, however at quite different percentages and levels. To understand the meaning of the biomarkers present in said CNPs, 10 samples showing the highest values for CNPs were selected for further analysis of biomarkers on the CNPs.
The data show clearly evident disease patterns easily recognized to the trained eyes of those skilled in the art. Especially prominent patterns were seen in prostatitis and prostate cancer. The establishment of these ratios and scatter graphs (see Figures 11 and 13 respectively) offer substantial improvements to the diagnosing of these diseases.
In prostate cancer and prostatitis, the most important biomarkers are the presence or absence or MHC-I, Macrophage Scavenger Receptor, Osteocalcin, PGRP-I, PSA5 Aquaporin-4. The results may be better analyzed by comparison of specific marker values to the capture results. In prostate cancer, the ratio of marker Macrophage 1:1.5 to (or and approximate 30 fold difference) capture, whereas in prostatitis the ratio is 1:0.5.
Similarly, the ratio result (prostate cancer) MHC-I to capture is about 5% whereas the ratio in Prostatitis is almost 1.0 or a 20 fold difference. Significantly, Osteocalcin shows importance as either a presence and absence value as it is not present in Cancer.
For PGRP-I, the difference is approximately 0.15 in Prostate Cancer and 0.8 in prostatitis, meaning approximately 5.5 fold.
PSA shows a value of approximately 0.076 in Prostatitis and 0.03 in prostate cancer, or approximately 2 fold differences. This is a very small factor in favor of prostate cancer. In TG2 (labvision) the difference is .0009 in Prostatitis and approximately 0.15 in prostate cancer, a difference of approximately 166 fold.
For Aquaporin, values show 0.8 in Prostatitis and 0.05 in prostate cancer, approximately a 20 fold increase in prostatitis.
Therefore, levels of these different markers are very important in the diagnosis of disease. For example, analysis via custer analysis that may involved sophisticated methods such as multivariate logistic regression.
In Psammoma Endometrioid adenocarecenoma, the most important biomarkers that are present or absent are MHC-I, Cystatin A, osteocalcin, PGRP-I Beeta, PSA, Labvisoin TG-2, Aquaporin-4. Psammoma Endometrioid adenocarecenoma had 8 groups with extremely high calcification that may be, for instance, easily separated by the correlation of the presence or absence MSR and PGRP-I Beeta and Aquaporin-4. Notable is that some normal positive high value had high PSA. Therefore, disease specific marker tests results indicate that since the measurements were made using human blood samples different patterns of antigens on CNP may be explained only by assuming that those markers were bound on the surface of the CNP at the specific location of the pathological process. Therefore, these markers as associated with the CNP may be used to diagnose pathological processes, diseases, and ongoing processes leading to pathological problems (risk analysis and therapy follow up). This is due to the fact that different tissue and cells contain different (and the same) types of specific markers. It is well known that markers for diseases can be present YEARS before the onset of disease. Therefore these biomarkers can detectable prior to clinical diagnosis of disease and may be used as risk factor analysis or early detection of diseases including, but are not limited to, for example, heart or circulatory diseases such as Arteriosclerosis, Atherosclerosis, Coronary Heart Disease, Chronic Heart Failure, Valve Calcifications, Arterial Aneurysms, Calcific Aortic Stenosis, Transient Cerebral Ischemia, Stroke, Peripheral Vascular Disease, Monckeberg's Disease, Vascular Thrombosis; Dental Diseases such as Dental Plaque, Gum Disease (dental pulp stones), calcification of the dentinal papilla, and Salivary Gland Stones; Chronic Infection Syndromes such as Chronic Fatigue Syndrome; Kidney and Bladder Stones, Gall Stones, Pancreas and Bowel Diseases such as Pancreatic Duct Stones, Crohn's Disease, Colitis Ulcerosa; Blood disorders; Adrenal Calcification; Liver Diseases such as Liver Cirrhosis and Liver Cysts; Testicular Microliths, Chronic Calculous Prostatitis, Prostate Calcification, Calcification in Hemodialysis Patients, Malacoplakia; Autoimmune Diseases such as Lupus Erythematosous, Schleroderma, Dermatomyositis, Cutaneous polyarteritis, Panniculitis (Septal and Lobular), Antiphospholipid Syndrome, Arteritis Nodosa, Thrombocytopenia, Hemolytic Anemia, Myelitis, Livedo Reticularis, Chorea, Migraine, Junvenile Dermatomyositis, Graves Disease, Chronic Thyroiditis, Hypothyreoidism, Type 1
Diabetes Mellitis, Addison's Disease, and Hypopituitarism; Placental and Fetal Disorders, Polycystic Kidney Disease, Glomerulopathies; Eye Diseases such as Corneal Calcifications, Cataracts, Macular Degeneration and Retinal Vasculature-derived Processes and other Retinal Degenerations; Retinal Nerve Degeneration, Retinitis, and Iritis; Ear Diseases such as Otosclerosis, Degeneration of Otoliths and Symptoms from the Vestibular Organ and Inner Ear (Vertigo and Tinnitus); Thyroglossal cysts, Thyroid Cysts, Ovarian Cysts; Cancer such as Meningiomas, Breast Cancer, Prostate Cancer, Thyroid Cancer, Serous Ovarian Adenocarcinoma; Skin diseases such as Calcinosis Cutis, Skin Stones, Calciphylaxis, Psoriasis, Eczema, Lichen Ruber Planus or Lichen Simple Cysts;, Choroid Plexus Calcification, Neuronal Calcification, Calcification of the FaIx Cerebri, Calcification of the Intervertebral Cartilage or Disc, Intercranial or Cerebral Calcification, Rheumatoid Arthritis, Calcific Tenditis, Oseoarthritis, Fibromyalgia, Bone Spurs, Diffuse Interstitial Skeletal Hyperostosis, Intracranial Calcifications such as Degenerative Disease Processes and Dementia; Erythrocyte-Related Diseases involving Anemia, Intraerythrocytic Nanobacterial Infection and Splenci Calcifications; Chronic Obstructive Pulmonary Disease, Broncholiths, Bronchial Stones, Neuropathy, Calcifications and Encrustations of Implants, Mixed Calcified Biofilms, and Myelodegenerative Disorders such as Multiple Sclerosis, Lou Gehrig's, and Alzheimer's Disease. D. Example 4
Evidence of various type of CNP
Biomarker patterns found indicate that various types of CNPs exist in the body of animal. The presence of different "types" has been verified by testing biodistribution in rats. Test results showed very different bio-distributions for the CNPs. It was determined that CNPs vary depending upon where they are harvested.
For example, CNPs taken from hosts and passage several times in various growth media, then injected into the tails of rats still showed specific characteristics depending upon original location of harvesting. Figure 12 shows the excretion in urine from a RAT. The excretion kinetics in the urine were very different. The most pronounced differentiation was shown with the Kindey stone isolate.
Table 8 is a list of some proteins that can be on CNPs. Table 9 is a list of proteins and compounds that can be associated with CNPs and proteins on CNPs. Table 10 shows calculated unit per ml data from 8 diseases using 14 markers and 10 patient samples for each disease. Table 11 shows the use of SAPIA technique to map Proteins associated with CNPS (Raw Data plus units per ml data). Table 12 shows a table on correlation on SAPIA results for various proteins and antigens on CNPs (coefficients and significances). Table 1. Bonferroni (Dunn) t Tests for Clotting Time
Difference Type Between Simultaneous 95% Comparison Means Confidence Limits
Clodrona- CaIEDTA 3.00 -134.38 140.38 Clodrona - Nontreat 38.68 -81.34 158.69 Clodrona - Nanobact 171.68 51.66 291.69 ***
Clodrona - Hydroxya 283.31 163.30 403.33 ***
CaIEDTA - Clodrona -3.00 -140.38 134.38 CaIEDTA - Nontreat 35.68 -84.34 155.69 CaIEDTA - Nanobact 168.68 48.66 288.69 ***
CaIEDTA - Hydroxya 280.31 160.30 400.33 ***
Nontreat - Clodrona -38.68 -158.69 81.34 Nontreat - CaIEDTA -35.68 -155.69 84.34 Nontreat - Nanobact 133.00 33.33 232.67 ***
Nontreat - Hydroxya 244.63 144.96 344.30 Nanobact - Clodrona -171.68 -291.69 -51.66 φ*φ
Nanobact - CaIEDTA -168.68 -288.69 -48.66 ***
Nanobact - Nontreat -133.00 -232.67 -33.33 H=**
Nanobact - Hydroxya 111.63 11.96 211.30 ***
Hydroxya - Clodrona -283.31 -403.33 -163.30 ***
Hydroxya - CaIEDTA -280.31 -400.33 -160.30 ***
Hydroxya - Nontreat -244.63 -344.30 -144.96 ***
Hydroxya - Nanobact -111.63 -211.30 -11.96 ***
Comparisons significant at the 0.05 level are indicated by ***. Table 2. Proteomic analysis of proteins on apatite particles briefly exposed to fetal bovine serum.
Protein name in the database %AA coverage Distinct Summed MS/MS Distinct
Search Score peptides
Serum albumin precursor 72 912.08 52
Apolipoprotein A-I precursor 52 321.51 18
Alpha- 1-antiproteinase precursor 39 261.59 14
IgGl heavy chain constant region 62 251.72 15
Alpha-2-HS-glycoprotein precursor 47 234.91 13
Vitamin K-dependent protein S precursor 22 221.73 13
Coagulation factor II 14 144.06 9
Endopin 1 27 131.14 8
Serotransferrin precursor 13 128.21 8
Anti-testosterone antibody 30 92.71 5
Hemoglobin alpha chain 22 78.07 5
Immunoglobulin light chain variable region 60 74.94 5
Hemoglobin beta fetal chain 30 73.16 4
Alpha-macroglobulin precursor 3 65.05 4
Ceruloplasmin 5 59.91 4
Inter-alpha-trypsin inhibitor H4 precursor 3 54.06 3
Beta-2-glycoprotein I 13 48.78 3
Immunoglobulin heavy chain constant region 10 48.58 3
C4b-binding protein alpha chain precursor 6 47.06 3
Vitronectin precursor 3 43.03 2
Ig lambda chain C region 18 33.32 2
Complement C3 precursor 1 32.27 2
IgG3 heavy chain constant region 5 28.10 2
Complement 9 2 21.00 1
Apolipoprotein A-II (antimicrobial peptide 21 21.00 1
BAMP-I)
Complement component C3 4 20.75 1
Coagulation factor V 0 19.47 1
RIKEN CDNA 2210010C04 4 19.14 1
Vitronectin precursor 2 16.83 1
Complement component 3 10 15.33 1
Alpha- 1-antichymotrypsin isoform pHHK12 3 14.65 1
Lipoprotein CIII 20 14.33 1
Adiponectin 6 13.71 1
Alpha-2-antiplasmin precursor 2 13.28 1 Table 3. List of antibodies used in the SAPIA test and immunohistochemical staining (IHS).
Antibody Supplier Clone Specificity Cross-reactivity ms Ref
Dilution α-prothrombin Biodesign 2A Human Not known 1:100 prothrombin, prethrombin 1 and fragment 2 α-prothrombin Cedarlane Affinity Fragment 1 region ND fragment 1 purified of human sheep prothrombin polyclonal α-thrombin Biodesign BDI905 Human thrombin Not known 1:100 α-Factor V American V237 Epitope on the Bovine factor V ND (20) Diagnostica light chain of and Va. human factor V. Binds to both factor V and factor Va. α-Factor VII USBiological 8.H.3 Human Factor VII, ND VHa, BFPRck Factor Vila α-Factor IX Biodesign 9D Human Factor IX Not known. 1:500 α-Factor X/Xa R&D Systems 156106 Human Factor X 1:100 and Xa. α-Factor XIIIA Labvision AC-IAl Human Factor Not known 1:100
XIΠA α-TF Calbiochem TF9- Human TF epitope 1:1000 (21) 10H10 locus I.
Recognized native, non-reduced and reduced human TF. α-TF-Vϋa American TF8-5G9 Human non- Not known ND (21).
Diagnostica reduced native TF and TF-VIIa complex. α-Fibrin(ogen) American Fl 3 Human fibrinogen No reactivity ND Diagnostica fragments D & for human DD, α, β, γ chains, fibrinogen early plasmin fragment E digestion fragments of fibrinogen α-chain α-Matrix GIa Alexis 52.1C5D Human Rat l:500a (22)
Biochemicals carboxylated and carboxylated non-carboxylated and non- matrix GIa protein carboxylated matrix GIa protein α-Osteocalcin Biodesign OCl Human/bovine Not known 1:51 (23) osteocalcin α-Fibronectin Labvision TV-I Human Pig, mouse and ND fibronectin. rat fibronectin. α-Human Biodesign 15C7 Human serum Not known. ND serum albumin albumin.
α-D-Dimer American DD- Human D-Dimer No cross ND Diagnostica 3B6/22 and cross-linked reactivity with fibrin derivatives human (DD-E). fibrinogen or fibrinogen degradation products.
CC-NF-KB ρ65 Labvision Rabbit Human Internal Rat and rabbit ND polyclonal domain of NF-κB Internal domain p65 of NF-KB p65 α-CNPs Nanobac Oy 8D10 Human CNPs Bovine CNPs 1:2° (2)
ND = not done a = pretreated by heating in microwave in 0.2% citric acid pH 6.0 for 15 minutes. Cooled at room temperature 15 minutes followed by washing three times with PBS. b = pretreated by heating in microwave in 0.01 M citric acid pH 6.0 for 20 minutes. Cooled at room temperature 1 h.
0 = culture supernatant
ATTORNEY DOCKET NO. 14151.0001P1
Table 4. Correlation between SAPIA and Nanocapture Elisa results. Pearson Correlation Coefficients (N = 16 Prob > |r| under HO: Rho=0) indicate presence of all clotting Gla-proteins and matrix-Gla protein in CNPs. Correlation coefficients are given,/? values in italics.
Capture a-FX/Xa a-FIX a-FVII a-mGLA p. a-FXIIIa a-fibrinogen a-FV a-TF-VIIa
Capture 1 0,62185 0,57671 0,67705 0,88105 0,61302 0,69009 0,59148 0,88746
0,0101 0,0194 0,0040 <,0001 0,0116 0,0031 0,0158 <,0001 a-FX/Xa 0,62185 1,00000 0,99729 0,98883 0,60706 0,97139 0,96756 0,99848 0,83422
0,0101 <,0001 <,0001 0,0126 <,0001 <,0001 <,0001 <,0001
a-FIX 0,57671 0,99729 1,00000 0,98139 0,58712 0,97522 0,96202 0,99792 0,81505
0,0194 <,0001 <,0001 0,0168 <,0001 <,0001 <,0001 0,0001 a-FVII 0,67705 0,98883 0,98139 1,00000 0,65116 0,97890 0,98065 0,98502 0,86068
0,0040 <,0001 <,0001 0,0063 <,0001 <,0001 <,0001 <,0001 a-mGLA p. 0,88105 0,60706 0,58712 0,65116 1,00000 0,64331 0,67566 0,57268 0,92621
<,0001 0,0126 0,0168 0,0063 0,0072 0,0041 0,0204 <,0001 a-FXIIIa 0,61302 0,97139 0,97522 0,97890 0,64331 1,00000 0,98412 0,97309 0,84151
0,0116 <,0001 <,0001 <,0001 0,0072 <,0001 <,0001 <,0001
a-fϊbrinogen 0,69009 0,96756 0,96202 0,98065 0,67566 0,98412 1,00000 0,96519 0,87082
0,0031 <,0001 <,0001 <,0001 0,0041 <,0001 <,0001 <,0001
a-FV 0,59148 0,99848 0,99792 0,98502 0,57268 0,97309 0,96519 1,00000 0,81100
0,0158 <,0001 <,0001 <,0001 0,0204 <,0001 <,0001 0,0001
a-TF-VIIa 0,88746 0,83422 0,81505 0,86068 96 0,92621 0,84151 0,87082 0,81100 1,00000
<,0001 <,0001 0,0001 <,0001 <,0001 <,0001 <,0001 0,0001
ATTORIsIEY DOCKET NO. 14151.0001P1
Table 5. Correlation for prothrombin fragments and osteocalcin in SAPIA and Nanocapture Elisa results. Pearson Correlation Coefficients (N = 16, Prob > |r[ under HO: Rho=0) indicate presence of prothrombin fragments, including thrombin, and osteocalcin in CNPs. Correlation coefficients are given,/? values in italics.
Capture a-Thrombin a-Prothr. Frag.l a-Prothr. Frag.2 a-Osteocalcin
i. Capture 1,00000 0,94414 0,66731 0,70832 0,72244 <,0001 0,0047 0,0021 0,0016
a-Thrombin 0,94414 1,00000 0,58615 0,74985 0,56848 <,0001 0,0170 0,0008 0,0216
a-Prothr. Frag.l 0,66731 0,58615 1,00000 0,38848 0,66931 0,0047 0,0170 0,1370 0,0046 a-Prothr. Frag.2 0,70832 0,74985 0,38848 1,00000 0,51525 0,0021 0,0008 0,1370 0,0411 a-Osteocalcin 0,72244 0,56848 0,66931 0,51525 1,00000 0,0016 0,0216 0,0046 0,0411
ATTORNEYDOCKETNO.14151.0001P1
Table 6. List of Antibodies.
Figure imgf000099_0001
ATTORNEYDOCKETNO.14151.0001P1
Figure imgf000100_0001
ATTORNEYDOCKETNO.14151.0001P1
Figure imgf000101_0001
ATTORNEYDOCKETNO.14151.0001P1
Figure imgf000102_0001
ATTORNEYDOCKETNO.14151.0001P1
Figure imgf000103_0001
ATTORNEYDOCKETNO.14151.0001P1
Figure imgf000104_0001
ATTORNEYDOCKETNO.14151.0001P1
Figure imgf000105_0001
ATTORNEYDOCKETNO.14151.0001P1
Figure imgf000106_0001
Table 7. Marker-Disease Correlations
Figure imgf000107_0001
Figure imgf000108_0001
Figure imgf000109_0001
Figure imgf000110_0001
Figure imgf000111_0001
Figure imgf000112_0001
Ill
Figure imgf000113_0001
Figure imgf000114_0001
Figure imgf000115_0001
Figure imgf000116_0001
Figure imgf000117_0001
Figure imgf000118_0001
Figure imgf000119_0001
Figure imgf000120_0001
Figure imgf000121_0001
Figure imgf000122_0001
Figure imgf000123_0001
Figure imgf000124_0001
Figure imgf000125_0001
Figure imgf000126_0001
Figure imgf000127_0001
Figure imgf000128_0001
Figure imgf000129_0001
Figure imgf000130_0001
Figure imgf000131_0001
Figure imgf000132_0001
Figure imgf000133_0001
Figure imgf000134_0001
Figure imgf000135_0001
Figure imgf000136_0001
Figure imgf000137_0001
Figure imgf000138_0001
Figure imgf000139_0001
Figure imgf000140_0001
Figure imgf000141_0001
Figure imgf000142_0001
Figure imgf000143_0001
Testican-3 precursor (SPARC/osteonectin, CWCV, and Kazal-like domains
TIC3 HUMAN (Q9BQ16) proteoglycan 3). {GENE: Name=SPOCK3; Synonyms=TICN3; ORFNames=UNQ409/PRO771} - Homo sapiens (Human)
Thrombomodulin precursor (TM) (Fetomodulin) (CD141 antigen). {GENE:
TRBM HUMAN (P07204) Name=THBD; Synonyms=THRM} - Homo sapiens (Human)
Uromodulin precursor (Tamm-Horsfall urinary glycoprotein) (THP). {GENE:
UROM HUMAN (P07911) Name=UMOD} - Homo sapiens (Human)
Visinin-like protein 1 (VILIP) (Hippocalcin-like protein 3) (HLP3). {GENE:
VISL1 HUMAN (P62760) Name=VSNL1 ; Synonyms=VISL1} - Homo sapiens (Human)
Table 9: Proteins that bind to Calcium Binding Proteins (CaBP-BP 's)
Figure imgf000145_0001
Figure imgf000146_0001
Figure imgf000147_0001
Figure imgf000148_0001
Figure imgf000149_0001
Figure imgf000150_0001
Figure imgf000151_0001
Figure imgf000152_0001
Figure imgf000153_0001
Figure imgf000154_0001
Figure imgf000155_0001
Figure imgf000156_0001
Figure imgf000157_0001
Figure imgf000158_0001
Figure imgf000159_0001
Figure imgf000160_0001
Figure imgf000161_0001
Figure imgf000162_0001
Figure imgf000163_0001
Figure imgf000164_0001
Figure imgf000165_0001
Figure imgf000166_0001
Figure imgf000167_0001
Figure imgf000168_0001
Figure imgf000169_0001
Figure imgf000170_0001
Figure imgf000171_0001
Figure imgf000172_0001
Figure imgf000173_0001
Figure imgf000174_0001
Figure imgf000175_0001
Figure imgf000176_0001
Figure imgf000177_0001
Figure imgf000178_0001
Figure imgf000179_0001
Figure imgf000180_0001
Figure imgf000181_0001
Figure imgf000182_0001
Figure imgf000183_0001
Figure imgf000184_0001
Figure imgf000185_0001
Figure imgf000186_0001
Figure imgf000187_0001
Figure imgf000188_0001
Figure imgf000189_0001
Figure imgf000190_0001
Figure imgf000191_0001
Figure imgf000192_0001
Figure imgf000193_0001
Figure imgf000194_0001
Figure imgf000195_0001
Figure imgf000196_0001
Figure imgf000197_0001
Figure imgf000198_0001
Figure imgf000199_0001
Figure imgf000200_0001
Figure imgf000201_0001
Myeloperoxidase
Figure imgf000201_0002
FIBRONECTIN
Figure imgf000202_0001
Figure imgf000203_0001
Figure imgf000204_0001
Figure imgf000205_0001
Figure imgf000206_0001
Figure imgf000207_0001
BSA
Figure imgf000207_0002
LBP
Figure imgf000207_0003
Figure imgf000208_0001
Figure imgf000209_0001
COMPLEMENT C5
Figure imgf000209_0002
Figure imgf000210_0001
Figure imgf000211_0001
Human gamma GIa
Figure imgf000211_0002
Figure imgf000212_0001
Figure imgf000212_0002
Annexin
Figure imgf000212_0003
Figure imgf000213_0001
Figure imgf000214_0001
Figure imgf000215_0001
Figure imgf000216_0001
Figure imgf000217_0001
Figure imgf000218_0001
Figure imgf000219_0001
Figure imgf000220_0001
Figure imgf000221_0001
Figure imgf000222_0001
Figure imgf000223_0001
Figure imgf000224_0001
Figure imgf000225_0001
gamma-carboxy glutamate
Figure imgf000225_0002
ATTORNEYDOCKETNO.14151.0001P1
90 Table 10
O O Cholecystitis
H U
O O r-- o
O O
Figure imgf000226_0001
O
ATTORNEYDOCKETNO.14151.0001P1
90 IΛ rr
O O rs Cholecystitis
U
O O
(-- (--
Figure imgf000227_0001
O O
O
ATTORNEYDOCKETNO.14151.0001P1
Kidney Stones
Figure imgf000228_0001
O O o
O O
O
Figure imgf000228_0002
ATTORNEYDOCKETNO.14151.0001P1
ft
O O Kidney Stones hi U
O O
O l~-
Figure imgf000229_0001
O O
O
ATTORNEY DOCKET NO. 14151.0001P1
90
5 Psommoma Endometrioid adenocarcinoma
O O
CΛ Macrophage Abeam
U scavenger Kallikrein Alpha- Troponin Transglutaminase
Capture MHC-I receptor Cystatin A 6 synuclein Osteonectin Osteocalcin C 2
Nan-04-289 511.902 640.000 39.515 26.824 1.954 45.569 0.808 3.206 1.211 0.093
Nan-04-290 482.080 640.000 49.795 24.256 2.880 43.601 1.459 3.842 1.490 0.187
Nan-04-291 477.375 640.000 46.383 23.139 2.880 39.601 1.273 3.842 1.304 0.466
Nan-04-292 394.152 640.000 44.134 23.913 2.418 37.551 0.994 3.630 1.211 0.093
Nan-04-293 470.192 640.000 45.208 25.456 2.880 43.601 2.387 3.206 1.490 0.839
Nan-04-294 343.062 640.000 40.458 25.798 1.954 43.247 1.087 3.206 1.118 1.118
Nan-04-295 482.237 640.000 76.910 28.189 1.304 46.656 1.459 3.630 0.653 0.373
Nan-04-296 413.482 640.000 48.215 29.382 0.932 42.018 0.901 2.352 0.932 0.093
Nan-04-315 14.989 0.200 11.784 5.908 0.653 14.396 0.435 0.191 0.093 0.093
Nan-04-316 14.936 0.107 13.005 2.973 0.093 10.908 0.342 0.000 0.000 0.000
Mean 360.441 512.031 41.541 21.584 1.795 36.715 1.114 2.710 0.950 0.336
SD 188.930 269.783 18.596 9.260 1.009 12.979 0.586 1.446 0.537 0.373
O Median 441.837 640.000 44.671 24.856 1.954 42.633 1.040 3.206 1.165 0.140 O
O O
O
ATTORNEY DOCKET NO. 14151.0001P1
ft
O O
hi
U
Psommoma Endometrioid adenocarcinoma
Labvision Aquaporin-
Capture PGRP-1 Beeta PSA Tgase 2 4
Nan-04-289 511.902 640.000 46.261 0.000 640.000
Nan-04-290 482.080 640.000 42.206 4.921 640.000
Nan-04-291 477.375 640.000 41.984 2.806
Nan-04-292 394.152 640.000 40.658 0.871 640.000
Nan-04-293 470.192 640.000 43.546 0.871 640.000
Nan-04-294 343.062 640.000 43.434 8.645 640.000
Nan-04-295 482.237 640.000 44.898 7.209
Nan-04-296 413.482 640.000 41.984 0.218 640.000
Nan-04-315 14.989 1.950 0.036 4.712 0.000
Nan-04-316 14.936 0.000 0.036 2.593 0.000
O O
O l~-
O O Mean 360.441 512.195 34.504 3.285 480.000
O SD 188.930 269.437 18.236 3.007 296.262
Median 441.837 640.000 42.095 2.700 640.000
ATTORNEYDOCKETNO.14151.0001P1
90
Prostate cancer
O O
U
O O
Figure imgf000232_0001
O
O O
O
ATTORNEYDOCKETNO.14151.0001P1
90 IΛ rr
O O rs
U
Prostate cancer
o
O
(--
O O
O
Figure imgf000233_0001
ATTORNEY DOCKET NO. 14151.0001P1
90
5 Prostatitis
O O
U
O O
Figure imgf000234_0001
O O
O
ATTORNEY DOCKET NO. 14151.0001P1
90
O O
U a.
Prostatitis
O O
O O
O
Figure imgf000235_0001
ATTORNEYDOCKETNO.14151.0001P1
so
Rheumatoid
© © arthritis
1*1
S3
© ©
©_
© ©
Figure imgf000236_0001
O
ATTORNEYDOCKETNO.14151.0001P1
90
O O
U a. Rheumatoid arthritis
O O
O O
O
Figure imgf000237_0001
ATTORNEYDOCKETNO.14151.0001P1
Aortic valve stenosis
Figure imgf000238_0001
O O r--
Figure imgf000238_0002
o
O O
O
ATTORNEYDOCKET NO. 14151.0001P1
90
O
Aortic valve stenosis
H u eh
O O r-- o
Figure imgf000239_0001
O O
O
ATTORNEYDOCKETNO.14151.0001P1
Parkinsons
Figure imgf000240_0001
O
Figure imgf000240_0002
O t~
O r-- o
O
O
ATTORNEYDOCKETNO.14151.0001P1
90
SM Parkinsons
Figure imgf000241_0001
© ©
Table 11. Use of SAPIA Technique to map proteins assocatied with CNPs (raw data plus units per ml data)
Capture Time DATA: Summary table of Data by MARKERS
Variable Label
Capture varl anti-Fetuin A var2 anti-calmodulin var3 anti-Tgase II var4 anti-MMP-9 var5 anti-MMP-3 var6 anti-CD 42b var7 NF-kappa B var8 anti-osteopontin var9 anti-Factor X/Xa varlO anti CD14 varll anti-prothrombin varl2 anti-Factor IX varl3 anti-Fetuin B varl4 anti-CD40 varl5 anti-myeloperoxidase varl6 vanti-Fibronectin varl7 anti-Factor VII varl8 anti-tissue factor varl9 anti-human complement 5b-9 var20 anti-human CRP var21 anti-matrix GLA var22 anti-CD61 var23 anti-Kappa Light Chain var24 anti-Macrophage var25 anti-factor XIIIA var26 anti-hsp 60 var27 anti-fibrillin-1 var28 anti-B2 microgl var29 anti-CD 18 var30 anti-laminin var31 anti-antitrypsin var32 anti-Notch-1 var33 anti-BSA var34 anti-LBP var35 anti-PTX3 var36 anti-complement C5 var37 anti-fibrinogen var38 anti-D-Dimer var39 anti-factor V var40 anti-human gamma-Gla var41 anti-TF-VIIa var42 anti-complement C3c var43 anti-Complement C4 var44 anti-antichymotrypsin var45 anti-Annexin V var46 anti-Lipid A var47 anti-isopeptide bond var48 anti-vitronectin var49 anti-thrombin var50 anti-osteocalcin var51 anti-Troponin T var52 anti-vimentin var53 a-tropomyosin var54 anti-HSA var55 Troponin I cardiac var56 anti-Apo Al var57 MHC class I var58 Amyloid P protein var59 anti-sCD40 L var60 anti-kallikrein var61 Anti-Prothr Fl var62 goat-ATIII var63 anti-Thrombin var64 anti-Factor VIII var65 anti-heparan Sulph var6S anti-Factor XI var67 anti-c-jun var68 anti-Fra-2 var69 anti-Fra-1 var70 anti-Jun B var71 anti-P-c-Jun var72 anti-TGase3 var73 anti-alpha fetoprotein var74 anti-PSA var75 anti-erbB2 var76 anti-VEGF var77 anti-alpha synuclein var78 anti-mucin-1 var79 anti-Cystatin A var80 anti-Cystatin S var81 Prostein var82 Aquaporin 4 var83 Trypsin var84 Osteonectin var85 RAGE var86 PGRP-I Beeta var87 PGRP-S var88 Gram positive bacteria var89 Troponin C Cardiac var90 Protein C var91 Macrophage Scavenger Receptor Type I var92 anti-anti-Thrombin var93 Protein S var94 BAFP
Figure imgf000243_0001
(Continued)
Figure imgf000244_0001
(Continued)
Figure imgf000244_0002
_ - - - Var52 16.00 4.06 0.00 34.41 0.00 0.00 4.08
Var53 IS. OO 1.04 0.00 9.61 0.00 0.00 0.00
Var54 16.00 0.54 0.00 5.03 0.00 0.00 0.00
VarS5 16.00 0.21 0.00 1.22 0.00 0.00 0.00
Var5S 16.00 14.45 0.00 125.7 0.00 0.00 0.S7
Var57 16.00|202.7 0.58 640.0 17.66 115.5 319.7
VarΞ8 16.00 4.28 0.10 8. SS 1.96 3.52 7.22
VarS9 16.00 23.01 0.12 110.2 1.33 6.61 32.00
Var6 16.00 65.25 1.03 156.5|l8.50 66.58 108.7
Var60 16.00 14.93 0.00 125.7 0.04 0.59 3.32
Varδl 16.00 10.00 0.00 80.84 0.00 0.49 7.68
Var62 16.00 10.27 0.00 49.02 1.19 3.33 11.75
(Continued)
values
Medi¬
N Mean Min Max Ql an Q3 markers
Var63 16.00 117.2 0.48 640.0 15.40 77.92 148.7
Var64 16.00 1.38 0.00 17.44 0.00 0.00 0.39
Var65 16.00|22.85 0.00 113.8 1.70 10.14 39.35
Var66 16.00 15.36 0.00 100.3 0.64 3.97 16.72
Var67 16.00 0.86 0.00 3.10 0.32 0.57 0.98
Var68 16.00 0.98 0.20 2.22 0.66 1.01 1.21
Var69 16.00 0.46 0.00 3.54 0.15 0.30 0.35
Var7 16.00 0.27 0.00 2.70 0.00 0.00 0.02
Var70 16.00 2.70 0.00 7.07 0.66 2.07 4.90
Var71 16.00 9.47 0.25 28.37 1.06 7.68 16.21
Var72 16.00 1.34 0.00 5.05 0.35 0.96 2.07
__ __ Var73 16.00 0.00 0.00 0.00 0.00 0.00 0.00
Var74 16.00 43.54 0.03|l03.9 12.06|40.71 76.21 _ _ __ Var75 16.00 3.80 0.00 11.18 0.96 3.09 5.60
Var76 16.00 5.63 0.00|l6.46 1.22 4.71 8.47
Var77 16.00 39.21 1.89 80.77 16.3l|38.95 64.15
Var78 16.00 0.79 0.00 4.47 0.06 0.11 0.76
Var79 16.00 10.32 0.00 34.51 2.40 10.54 16.56
Var8 16.00 0.93 0.00 3.56 0.00 0.68 1.54 Var80 16.00 9.41 0.00|22.97 1.98 8.50 15.98| I 1
(Continued) __ _ l values
__ _ _ _ _
Medi¬
N Mean Min Max Ql an Q3 markers
__ _ __ _ __ Var81 12.00 0.63 0.00 2.84 0.26 0.36 0.80
Var82 12.00 153.8 0.94 640.0 8.84 65.15 208.2
Var83 12.00 105.8 0.51 529.4 8.37 44.11 106.6
I
Var84 12.00 22.14 0.07 239.8 0.29 1.21 2.50
Var85 12.00 3.58 0.00 12.18 0.42 2.57 5.01
Var86 16.00 302.7 0.47 640.0 17.40 127.1 640.0
Var87 14.00 250.0 0.00 640.0 11.14 83.15 574.3
I
Var88 14.00 0.36 0.00 2.92 0.00 0.05 0.32
Var89 14.00 27.09 0.00|241.9 0.00 0.87 6.52
Var9 16.00 12.07 0.00 124.1 0.00 1.97 6.80
Var90 14.00 0.16 0.00 1.91 0.00 0.00 0.00
Var91 14.00 27.05 1.4B|l52.3 3.32 14.78 27.53
Var92 IS.00 7.81 0.00 50.66 0.00 1.49 7.46
Var93 16.00 1.47 0.00|20.10 0.00 0.00 0.40
Var94 16.00 0.00 0.00 0.00 0.00 0.00 0.00
Simple Statistics
Variable N Mean Std Dev Sum Minimum Maximum
Capture 16 253.06400 217.10056 4049 0 640.00000 varl 16 42.39131 36.97189 678.26100 1.17000 130.51800 var2 16 2.87156 5.25100 45.94500 0.08500 21.84000 var3 16 6.87844 14.85900 110.05500 0.34200 60.35300 var4 16 5.62819 12.59201 90.05100 0 51.61700 var5 16 0.89450 1.04024 14.31200 0 3.13200 var6 16 65.25106 50.53021 1044 1.02700 156.47900 var7 16 0.26788 0.73790 4.28600 0 2.70200 var8 16 0.93481 1.12028 14.95700 0 3.56300 var9 16 12.06594 30.70712 193.05500 0 124.10700 varlO 16 4.57550 11.25589 ' 73.20800 0 45.74200 varll 16 0.91200 1.57184 14.59200 0 4.72800 varl2 16 11.52425 30.57534 184.38800 0 124.50100 varl3 16 57.37475 64.84223 917.99600 0.25600 253.52800 varl4 16 0.20106 0.58191 3.21700 0 2.32400 varl5 16 2.74681 2.10943 43.94900 0.32100 9.43600 varl6 16 7.23081 12.24811 115.69300 0.06400 48.90700 varl7 16 8.48956 14.43197 135.83300 0.83000 59.36700 varl8 16 6.82150 14.44434 109.14400 0 58.26500 varl9 16 0.69163 2.22119 11.06600 0 8.90200 var20 16 0.77719 2.28338 12.43500 0 8.51500 var21 16 126.07219 108.26025 2017 2.92400 342.73900 var22 16 4.26063 5.96719 68.17000 0 22.51500 var23 16 1.63538 1.71553 26.16600 O 6.59400 var24 IS 3.62650 4.37522 58.02400 0.06400 17.94700 var25 16 1.72625 3.28336 27.62000 O 13.38700 var26 16 1.54344 2.50923 24.69500 O 10.29700 var27 16 4.08681 8.85404 65.38900 0.07100 36.23900 var28 16 O .76188 1.09194 12.19000 O 2.82900 var29 16 1.86238 4.14488 29.79800 0.04600 16.69300 var30 16 0.68919 1.17260 11.02700 O 4.59700 var31 16 0.64381 0.87088 10.30100 O 3.49800 var32 16 5.45506 4.48899 87.28100 O 12.28800 var33 16 11.60594 25.43922 185.59500 0.29600 101.52500 var34 16 4.93469 13.56550 78.95500 O 52.46400 var35 16 0.01056 0.02338 0.16900 O 0.07000 var3S 16 0.36519 1.07551 5.84300 O 4.35900 var37 16 4.64031 7.83236 74.24500 O 31.41500 var38 16 O .11931 0.30392 1.90900 O 1.10900 var39 16 7.39944 19.88615 118.39100 O 80.24500 var40 16 0.74363 1.43253 11.89800 O 4.43100 var41 16 20.46100 21.12955 327.37600 O 80.53500 var42 16 0.34069 0.68747 5.45100 O 2.67800 var43 16 0.33200 0.99070 5.31200 O 3.88600 var45 16 0.32513 0.68749 5.20200 O 2.02500 var46 16 0.51231 0.72217 8.19700 O 2.92600 var47 16 0.41181 0.46771 6.58900 O 1.69300 var48 16 4.27238 3.81834 68.35800 0.21700 13.13000 var49 16 274.29412 260.86792 4389 1.88300 640.00000 var50 16 85.43369 197.39999 1367 O 602.03800 var51 16 6.01763 6.88874 96.28200 O 26.83800 var52 16 4.05869 8.84811 64.93900 O 34.40900 var53 16 1.03713 2.58091 16.59400 O 9.61100 var54 16 0.54319 1.45735 8.69100 O 5.02500 var55 16 0.20763 0.44867 3.32200 O 1.22200 var5S 16 14.45100 38.87846 231.21600 O 125.71300 var57 16 202.73894 238.71781 3244 0.58400 640.00000 var58 16 4.27713 2.96205 68.43400 0.09700 8.64500 var59 16 23.00694 34.06665 368.11100 0.12000 110.20800 var60 16 14.93225 38.02049 238.91600 O 125.74400 var61 16 10.00131 22.36333 160.02100 O 80.84200 var62 16 10.27450 14.95231 164.39200 O 49.02000 var63 16 117.18013 158.07018 1875 0.48100 640.00000 var64 16 1.38181 4.33492 22.10900 O 17.44400 var65 16 22.85213 30.42459 365.63400 O 113.78900 var66 16 15.36038 26.24358 245.76600 O 100.25900 var67 16 0.86044 0.91891 13.76700 O 3.09800 var68 16 0.98475 0.50500 15.75600 0.20200 2.22200 var69 16 0.46081 0.83284 7.37300 O 3.53500 var70 16 2.69563 2.28526 43.13000 O 7.07100 var71 16 9.46619 9.10550 151.45900 0.25300 28.36700 var72 ■ 16 1.34463 1.29190 21.51400 O 5.05100 var74 16 43.54356 34.96082 696.69700 0.02500 103.90400 var75 16 3.80356 3.51674 60.85700 O 11.17900 var76 16 5.63056 5.29653 90.08900 O 16.45900 var77 16 39.21356 27.55760 627.41700 1.89300 80.76600 var78 16 0.78650 1.32865 12.58400 O 4.46600 var79 16 10.31588 9.45851 165.05400 O 34.50600 var80 16 9.41475 8.02499 150.63600 O 22.97200 varδl 13 0.78431 0.90546 10.19600 O 2.84200 var82 13 191.17715 242.13190 2485 0.94300 640.00000 var83 13 146.36031 210.81152 1903 0.50900 633.40600 var84 13 38.64208 88.67047 502.34700 0.07300 239.77100 var85 13 4.07300 4.12665 52.94900 O 12.17500 var86 16 302.69400 307.07168 4843 0.46800 640.00000 var87 15 237.47640 265.70065 3562 O 640.00000 var88 15 0.33900 0.75763 5.08500 O 2.92300 var89 15 25.40413 66.59440 381.06200 O 241.92100 var90 15 0.18747 0.50593 2.81200 O 1.91100 var91 15 27.10693 38.25447 406.60400 1.47800 152.32500 var92 16 7.80681 14.72424 124.90900 O 50.65800 var93 16 1.47194 4.98897 23.55100 O 20.10300 Correlation Analysis Results:
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations
Capture varl var2 var3
Capture 1.00000 0.93991 0.63286 0.56886
<.0001 0.0085 0.0215
16 16 16 16 varl 0.93991 1.00000 0.76597 0.69788 anti-Fetuin A <.0001 0.0005 0.0026
16 16 16 16 var2 0.63286 0.76597 1.00000 0.98310 anti-calmodulin 0.0085 0.0005 <.0001
16 16 16 16 var3 0.56886 0.69788 0.98310 1.00000 anti-Tgase II 0.0215 0.0026 <.0001
16 16 16 16 var4 0.58481 0.72299 0.99419 0.99522 anti-MMP-9 0.0173 0.0016 <.0001 <.0001
16 16 16 16 var5 0.58183 0.63641 0.40855 0.31555 anti-MMP-3 0.0181 0.0080 0.1162 0.2338
16 16 16 IS var6 0.90051 0.93484 0.62866 0.55540 anti-CD 42b <.0001 <.0001 0.0091 0.0255
16 16 16 16 var7 0.17190 0.31429 0.49314 0.47198
NF-kappa B 0.5244 0.2358 0.0523 0.0649
16 16 16 16 var8 0.65029 0.72953 0.65846 0.61872 anti-osteopontin 0.0064 0.0013 0.0055 0.0106
16 16 16 16 var9 0.62185 0.74939 0.98142 0.97553 anti-Factor X/Xa 0.0101 0.0008 <.0001 <.0001
16 16 16 16 varlO 0.57969 0.71543 0.99201 0.99590 anti CD14 0.0186 0.0018 ■c.OOOl <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var4 var5 var6 var7
Capture 0.58481 0.58183 0.90051 0.17190
0.0173 0.0181 <.0001 0.5244
16 16 16 16 varl 0.72299 0.63641 0.93484 0.31429 anti-Fetuin A 0.0016 0.0080 <.0001 0.2358
16 16 16 16 var2 0.99419 0.40855 0.62866 0.49314 anti-calmodulin <.0001 0.1162 0.0091 0.0523 16 16 16 16 var3 0.99522 0.31555 0.55540 0.47198 anti-Tgase II <.0001 0.2338 0.0255 0.0649
16 16 16 16 var4 1.00000 0.34598 0.58010 0.48042 anti-MMP~9 0.1893 0.0185 0.0596
16 16 16 16 var5 0.34598 1.00000 0.59898 0.63782 anti-MMP-3 0.1893 0.0142 0.0079
16 16 16 16 var6 0.58010 0.59898 1.00000 0.23898 anti-CD 42b 0.0185 0.0142 0.3727
16 16 16 16 var7 0.48042 0.63782 0.23898 1.00000 NF-kappa B 0.0596 0.0079 0.3727
16 16 16 16 var8 0.62453 0.82557 0.69888 0.81215 anti-osteopontin 0.0097 <.0001 0.0026 0.0001
16 16 16 16 var9 0.98511 0.32463 0.56932 0.41401 anti-Factor X/Xa <.0001 0.2199 0.0213 0.1109
16 16 16 16 varlO 0.99928 0.33104 0.56695 0.48624 anti CD14 <.0001 0.2104 0.0220 0.0562
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var8 var9 varlO varll
Capture 0.65029 0.62185 0.57969 0.70832
0.0064 0.0101 0.0186 0.0021
16 16 16 16 varl 0.72953 0.74939 0.71543 0.63724 anti-Fetuin A 0.0013 0.0008 0.0018 0.0079
16 16 16 16 var2 0.65846 0.98142 0.99201 0.22354 anti-calmodulin 0.0055 <.0001 <.0001 0.4053
16 16 16 16 var3 0.61872 0.97553 0.99590 0.11153 anti-Tgase II 0.0106 <.0001 <.0001 0.6809
16 16 16 16 var4 0.62453 0.98511 0.99928 0.14631 anti-MMP-9 0.0097 <.0001 <.0001 0.5887
16 16 16 16 var5 0.82557 0.32463 0.33104 0.69878 anti-MMP-3 <.0001 0.2199 0.2104 0.0026
16 16 16 16 var6 0.69888 0.56932 0.56695 0.55757 anti-CD 42b 0.0026 0.0213 0.0220 0.0248
16 16 16 16 var7 0.81215 0.41401 0.48624 0.01608 NF-kappa B 0.0001 0.1109 ' 0.0562 0.9529
16 16 16 16 var8 1.00000 0.56718 0.62165 0.42121 anti-osteopontin 0.0219 0.0101 0.1042
IS 16 16 16 var9 0.56718 1 .00000 0 -98625 0.20805 anti-Factor X/Xa 0.0219 <.0001 0.4394
16 16 16 16 varlO 0.62165 0 .98625 1 -00000 0.13315 anti CD14 0.0101 <.0001 0.6230
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations varl2 varl3 varl4 varl5
Capture 0.57671 0.88442 0.05923 0.28195
0.0194 <.0001 0.8275 0.2901
16 16 16 16 varl 0.71641 0.96367 0.15111 0.34949 anti-Fetuin A 0.0018 <.0001 0.5764 0.1845
16 16 16 16 var2 0.98449 0.89303 0.23225 0.41062 anti-calmodulin <.0001 <.0001 0.3867 0.1141
16 16 16 16 var3 0.98157 0.84782 0.20211 0.35023 anti-Tgase II <.0001 <.0001 0.4529 0.1836
16 16 16 16 var4 0.99094 0.86772 0.20835 0.36891 anti-MMP-9 <.0001 <.0001 0.4387 0.1597
16 16 16 16 var5 0.29848 0.52688 0.63685 0.80332 anti-MMP-3 0.2615 0.0360 0.0080 0.0002
16 16 16 16 var6 0.54529 0.86044 0.13309 0.32601 anti-CD 42b 0.0289 <.0001 0.6232 0.2179
16 16 16 16 var7 0.42396 0.34154 0.94828 0.90119 NF-kappa B 0.1017 0.1954 <.0001 <.0001
16 16 16 16 var8 0.55314 0.68982 0.74645 0.81846 anti-osteopontin 0.0262 0.0031 0.0009 0.0001
16 16 16 16 var9 0.99729 0.89231 0.13080 0.29691 anti-Factor X/Xa <.0001 <.0001 0.6292 0.2641
16 16 16 16 varlO 0.99154 0.86294 0.21406 0.36585 anti CD14 <.0001 <.0001 0.4260 0.1635
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations varl6 varl7 varl8 varl9
Capture 0 .51899 0 .67705 0 .64129 0 .49770
0.0394 0.0040 0.0074 0.0498
16 16 16 16 varl 0 .61993 0 .79587 0 .76742 0 .65791 anti-Fetuin A 0.0104 0.0002 0.0005 0.0056
16 16 16 16 var2 0.92951 0.98452 0.98947 0.97407 anti-calmodulin <.0001 <.0001 <.0001 <.0001
16 16 16 16 var3 0.94957 0.97122 0.98767 0.95984 anti-Tgase II <.0001 <.0001 <.0001 <.0001
16 16 16 16 var4 0.94567 0.97960 0.99139 0.97578 anti-MMP-9 <.0001 <.0001 <.0001 <.0001
16 16 16 16 varΞ 0.30536 0.44636 0.38813 0.29682 anti-MMP-3 0.2501 0.0831 0.1374 0.2643
16 16 16 16 var6 0.47516 0.61878 0.61754 0.51326 anti-CD 42b 0.0629 0.0106 0.0108 0.0420
16 16 16 16 var7 0.47331 0.48916 0.42528 0.53231 NP-kappa B 0.0641 0.0545 0.1006 0.0338
16 16 16 16 var8 0.59266 0.66521 0.62493 0.59215 anti-osteopontin 0.0155 0.0049 0.0096 0.0157
16 16 16 16 var9 0.92467 0.98883 0.98468 0.96146 anti-Factor X/Xa <.0001 <.0001 <.0001 <.0001
16 16 16 16 varlO 0.94549 0.97991 0.98848 0.97778 anti CD14 ■c.OOOl <.0001 <-0001 <.0001
16 16 16 IS
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var20 var21 var22 var23
Capture 0.47936 0.88105 0.21537 0.41533
0.0603 <.0001 0.4231 0.1096
16 16 16 16 varl 0.60423 0.93081 0.25789 0.46120 anti-Fetuin A 0.0132 <.0001 0.3349 0.0722
16 16 16 16 var2 0.91784 0.67281 0.39993 0.52797 anti-calmodulin <.0001 0.0043 0.1248 0.0355
16 16 16 16 var3 0.96775 0.58348 0.37305 0.48608 anti-Tgase II <.0001 0.0177 0.1547 0.0563
16 16 16 16 var4 0.94614 0.61876 0.38151 0.49693 anti-MMP-9 <.0001 0.0106 0.1448 0.0502
16 16 15 16 var5 0.17637 0.61698 0.36635 0.74506 anti-MMP-3 0.5135 0.0109 0.1628 0.0009
16 16 16 16 vars 0.49394 0.98125 0.26629 0.40273 anti-CD 42b 0.0518 <.0001 0.3188 0.1220
16 16 16 16 var7 0.34426 0.23612 0.24225 0.90335 NF-kappa B 0.1917 0.3786 0.3660 <.0001 16 16 16 16 var8 0.51585 0.68745 0.25991 0.86217 anti-osteopontin* 0.0408 0.0033 0.3310 <-0001
16 16 16 16 var9 0.91038 0.60706 0.35075 0.44674 anti-Factor X/Xa <.0001 0.0126 0.1829 0.0828
16 16 16 16 varlO 0.94551 0.60270 0.37088 0.50100 anti CD14 ■c.0001 0.0135 0.1573 0.0481
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var24 var25 var26 var27
Capture 0.46976 0.61302 0.66343 0.58715
0.0664 0.0116 0.0051 0.0168
16 16 16 16 varl 0.58079 0.74598 0.80077 0.72483 anti-Fetuin A 0.0183 0.0009 0.0002 0.0015
16 16 16 16 var2 0.89027 0.99224 0.99203 0.98986 anti-calmodulin <.0001 <.0001 <.0001 <.0001
16 16 16 16 var3 0.88540 0.99314 0.96453 0.99690 anti-Tgase II <.0001 <.0001 <.0001 <.0001
16 16 16 16 var4 0.89062 0.99360 0.97699 0.99862 anti-MMP-9 <.0001 <.0001 <.0001 <.0001
15 16 16 16 var5 0.34946 0.40201 0.49105 0.33755 anti-MMP-3 0.1846 0.1227 0.0534 0.2010
16 16 16 16 var6 0.47073 0.61145 0.66429 0.58375 anti-CD 42b 0.0657 0.0118 0.0050 0.0176
16 16 16 16 var7 0.41264 0.51384 0.53450 0.47275 NF-kappa B 0.1122 0.0417 0.0329 0.0644
16 16 16 16 var8 0.49953 0.68161 0.71667 0.62376 anti-osteopontin 0.0488 0.0036 0.0018 0.0098
16 16 16 16 var9 0.87154 0.97139 0.96222 0.98317 anti-Factor X/Xa <.0001 <.0001 <.0001 <.0001
16 16 16 16 varlO 0.88663 0.99240 0.97365 0.99802 anti CD14 <.0001 <.0001 <.0001 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var28 var29 var30 var31
Capture 0.54689 0.57128 0.29338 0.35605
0.0284 0.0208 0.2701 0.1759
16 16 16 16 varl 0.53057 0.49230 0.39162 0.43030 anti-Fetuin A 0.0345 0.0527 0.1336 0.0962
16 16 16 16 var2 0.21140 0.10049 0.46122 0.42276 anti-calmodulin 0.4319 0.7112 0.0722 0.1028
IS 16 16 16 var3 0.08364 0.04146 0.42606 0.38843 anti-Tgase II 0.7581 0.8788 0.0999 0.1371
16 16 16 16 var4 0.12816 0.05860 0.43513 0.39298 anti-MMP-9 0.6362 0.8293 0.0921 0.1321
16 16 16 16 var5 0.89012 0.55910 0.73362 0.79589 anti-MMP-3 <.0001 0.0243 0.0012 0.0002
16 16 16 16 var6 0.52671 0.30744 0.34039 0.39268 anti-CD 42b 0.0361 0.2467 0.1970 0.1324
16 16 16 16 var7 0.43907 0.01747 0.97764 0.93324 NF-kappa B 0.0889 0.9488 <.0001 <.0001
16 16 16 16 var8 0.67164 0.26612 0.87649 0.91061 anti-osteopontin 0.0044 0.3191 <.0001 <.0001
16 16 16 16 var9 0.12094 0.17435 0.37080 0.32715 anti-Factor X/Xa 0.6555 0.5184 0.1574 0.2161
16 16 16 16 varlO 0.11438 0.05671 0.43926 0.39483 anti CD14 0.6732 0.8348 0.0887 0.1302
16 16 16 16
Pearson Correlation Coefficients Prob > |r] under HO: RhO=O Number of Observations var32 var33 var34 var35
Capture -0.06698 0.65841 0.60363 0.07772
0.8053 0.0056 0.0133 0.7748
16 16 16 16 varl 0.06560 0.77003 0.70955 0.25857 anti-Fetuin A. 0.8093 0.0005 0.0021 0.3336
16 16 16 16 var2 -0.06241 0.96906 0.95087 0.57869 anti-calmodulin 0.8184 <-0001 <.0001 0.0188
16 16 16 16 var3 -0.16035 0.96654 0.92782 0.60340 anti-Tgase II 0.5530 <.0001 <.0001 0.0133
16 16 16 16 var4 -0.11793 0.97197 0.94046 0.61061 anti-MMP-9 0.6636 <.0001 <.0001 0.0120
16 16 . 16 16 var5 0.44092 0.36622 0.26377 -0.09396 anti-MMP-3 0.0874 0.1630 0.3236 0.7293
16 16 16 16 var6 0.05534 0.57620 0.59200 0.08403 anti-CD 42b 0.8387 0.0195 0.0157 0.7570
16 16 16 16 var7 0.30892 0.39922 0.36591 0.20732
NF-kappa B 0.2443 0.1256 0.1634 0.4410
16 16 16 16 var8 0.26533 0.58095 0.55675 0.12530 anti-osteopontin 0.3206 0.0183 0.0251 0.6438
16 16 16 16 var9 0.14116 0.99365 0.92864 0.62035 anti-Factor X/Xa 0.6021 <.0001 <.0001 0.0104
16 16 16 16 varlO 0.12839 0.97282 0.94101 0.61538 anti CD14 0.6356 <.0001 <.0001 0.0112
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var36 var37 var38 var39
Capture 0.50372 0.69009 0.37031 0.59148
0.0467 0.0031 0.1580 0.0158
16 16 16 16 varl 0.66261 0.79671 0.52970 0.71951 anti-Fetuin A 0.0052 0.0002 0.0348 0.0017
16 16 16 16 var2 0.97807 0.97580 0.49388 0.97935 anti-calπiodulin <-0001 <.0001 0.0519 <.0001
16 16 16 16 var3 0.96763 0.97655 0.41161 0.98118 anti-Tgase II <.0001 <.0001 0.1132 <.0001
16 16 16 16 var4 0.98091 0.97352 0.46439 0.98705 anti-MMP-9 <.0001 <.0001 0.0700 <.0001
16 16 16 16 var5 0.27642 0.41830 0.54893 0.29504 anti-MMP-3 0.3000 0.1069 0.0277 0.2673
16 16 16 16 var6 0.51641 0.64895 0.52695 0.53743 anti-CD 42b 0.0406 0.0065 0.0360 0.0318
16 16 16 16 var7 0.50034 0.41141 0.14459 0.42224 NF-kappa B 0.0484 0.1134 0.5932 0.1033
16 16 16 16 var8 0.57206 0.65306 0.35461 0.55581 anti-osteopontin 0.0206 0.0061 0.1778 0.0254
16 16 16 16 var9 0.96882 0.96756 0.44673 0.99848 anti-Factor X/Xa ■c.OOOl <.0001 0.0828 <.0001
16 16 16 16 varlO 0.98274 0.97110 0.43407 0.98936 anti CD14 <.0001 <.0001 0.0930 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var40 var41 var42 var43 Capture 0.71298 0.88746 0.47842 0.41587
0.0019 <.0001 0.0608 0.1091
16 16 16 16 varl 0.82790 0.97162 0.62818 0.56614 anti-Fetuin A <.0001 <.0001 0.0092 0.0222
16 16 16 16 var2 0.76182 0.85852 0.86629 0.91864 anti-calmodulin 0.0006 <.0001 <-0001 <.0001
16 16 16 16 var3 0.70055 0.80681 0.86555 0.92626 anti-Tgase II 0.0025 0.0002 <.0001 <.0001
16 16 16 16 var4 0.73614 0.82823 0.87736 0.93376 anti-MMP-9 0.0011 <.0001 <.0001 <.0001
16 16 IS 16 var5 0.60405 0.54333 0.20110 0.19627 anti-MMP-3 0.0132 0.0296 0.4552 0.4663
16 16 IS 16 var6 0.65865 0.92353 0.45404 0.42876 anti-CD 42b 0.005S <-0001 0.0773 0.0975
16 16 16 IS var7 0.24298 0.32507 0.35220 0.39611
NF-kappa B 0.3645 0.2193 0.1809 0.1288
16 16 16 16 var8 0.52423 0.70764 0.40104 0.43000 anti-osteopontin 0.0371 0.0022 0.1237 0.0964
16 16 16 16 var9 0.78834 0.83422 0.90526 0.92716 anti-Factor X/Xa 0.0003 <.0001 <.0001 <.0001
16 16 16 16 varlO 0.72223 0.82004 0.88148 0.93429 anti CD14 0.0016 0.0001 <.0001 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var45 var46 var47 var48
Capture 0.03495 0.21956 0.55360 0.79115
0.8977 0.4139 0.0261 0.0003
16 16 16 16 varl 0.15964 0.26315 0.67480 0.83565 anti-Fetuin A 0.5548 0.3248 0.0041 <.0001
16 16 16 16 var2 0.29020 0.23719 0.76636 0.41706 anti-calmodulin 0.2756 0.3764 0.0005 0.1080
16 16 16 IS var3 0.30545 0.19732 0.70764 0.31431 anti-Tgase II 0.2500 0.4639 0.0022 0.2358
16 16 16 16 var4 0.31538 0.20853 0.74546 0.35799 anti-MMP-9 0.2341 0.4383 0.0009 0.1734
16 16 16 16 var5 -0.14667 0.73822 0.43452 0.69951 anti-MMP-3 0.5878 0.0011 0.0926 0.0026
16 16 16 16 var6 0.10421 0.25282 0.57691 0.87166 anti-CD 42b 0.7009 0.3448 0.0193 <,0001
16 IS 16 16 var7 0.06172 0.86477 0.19175 0.09382
NF-kappa B 0.8204 <.O001 0.4768 0.7296
16 16 16 16 var8 0.03383 0.78915 0.44063 0.55368 anti-osteopontin 0.9010 0.0003 0.0876 0.0261
16 16 16 16 var9 0.32514 0.14419 0.75133 0.37987 anti-Factor X/Xa 0.2191 0.5942 0.0008 0.1467
16 16 16 16 varlO 0.31803 0.20798 0.72932 0.33594 anti CD14 0.2300 0.4396 0.0013 0.2033
16 16 16 IS
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var49 var50 var51 var52
Capture 0.94414 0.72244 0.57268 0.63099
<.0001 0.0016 0.0204 0.0088
16 16 16 16 varl 0.91683 0.75733 _ 0.64825 0.75103 anti-Fetuin A <.0001 0.0007 0.0066 0.0008
IS 16 16 16 var2 0.52135 0.75291 0.87832 0.96176 anti-calmodulin 0.0384 0.0008 <.0001 <.0001
16 16 16 16 var3 0.42238 0.73235 0.90882 0.97582 anti-Tgase II 0.1031 0.0013 <.0001 <.0001
16 IS 16 16 var4 0.46083 0.74009 0.89003 0.97125 anti-MMP-9 0.0724 0.0010 <.0001 ■=.0001
16 16 16 16 var5 0.60215 0.42892 0.46340 0.36698 anti-MMP-3 0.0136 0.0974 0.0706 0.1621
16 16 16 16 var6 0.93105 0.49309 0.50840 0.61073 anti-CD 42b <.0001 0.0523 0.0443 0.0120
16 16 16 16
var7 0.08564 0.28445 0.56279 0.37175 NF-kappa B 0.7525 0.2856 0.0232 0.1562
16 16 16 16 var8 0.57969 0.48975 0.68347 0.60284 anti-osteopontin 0.0186 0.0542 0.0035 0.0134
16 16 16 16 var9 0.49640 0.82780 0.86965 0.95951 anti-Factor X/Xa 0.0505 <.0001 <.0001 <.0001
16 16 16 16 varlO 0.44806 0.74625 0.89152 0.96673 anti CD14 0.0818 0.0009 <.0001 <-0001
16 16 16 16
Pearson Correlation Coefficients Prob > I rI under HO : Rho=0 Number of Observations var53 var54 var55 var56
Capture 0.43379 0.48395 0.64933 0.69446
0.0932 0.0575 0.0065 0.0028
16 16 16 16 varl 0.59600 0.36530 0.74974 0.75106 anti-Fetuin A 0.0148 0.1641 0.0008 0.0008
16 16 16 16 var2 0.92297 0.10316 0.62637 0.79709 anti-calmodulin <.0001 0.7038 0.0094 0.0002
16 16 16 16 var3 0.94925 0.15254 0.54707 0.77993 ant±-Tgase II <.0001 0.5728 0.0283 0.0004
IS 16 16 16 var4 0.93901 0.10624 0.59234 0.78983 anti-MMP-9 <.0001 0.6954 0.0156 0.0003
16 16 16 16 var5 0.39691 0.30313 0.63205 0.38871 anti-MMP-3 0.1280 0.2538 0.0086 0.1368
16 16 16 16 varβ 0.47832 0.21445 0.59726 0.48720 anti-CD 42b 0.0609 0.4251 0.0146 0.0556
16 16 16 16 var7 0.69094 -0.07686 0.16578 0.29890 NF-kappa B 0.0030 0.7772 0.5395 0.2608
16 16 16 16 var8 0.73244 0.23078 0.43852 0.47836 anti-osteopontin 0.0013 0.3898 0.0893 0.0609
16 16 16 16 var9 0.88444 0.17287 0.65086 0.87310 anti-Factor X/Xa <.0001 0.5220 0.0063 <.O001
16 16 16 16 varlO 0.94098 0.11055 0.57397 0.79596 anti CD14 <.0001 0.6836 0.0201 0.0002
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var57 var58 var59 var60
Capture 0.80940 0.87903 0.81297 0.70252
0.0001 <.0001 0.0001 0.0024
16 16 16 16 varl 0.81508 0.84176 0.85281 0.70978 anti-Fetuin A 0.0001 <.0001 <.0001 0.0021
16 16 16 16 var2 0.61271 0.58190 0.80618 0.63399 anti-calmodulin 0.0116 0.0180 0.0002 0.0084
16 16 16 16 var3 0.50427 0.50814 0.72366 0.61426 anti-Tgase II 0.0464 0.0445 0.0015 0.0114
16 16 16 16 var4 0.55305 0.53091 0.75251 0.62090 anti-MMP-9 0.0263 0.0343 0.0008 0.0103
16 16 16 16 var5 0.57313 0.76733 0.58350 0.41865 anti-MMP-3 0.0203 0.0005 0.0177 0.1065
16 16 16 16 var6 0.85634 0.86073 0.76827 0.43998 anti-CD 42b <.0001 <.0001 0.0005 0.0881
16 16 16 16 var7 0.15782 0.40620 0.31165 0.21638 NF-kappa B 0.5594 0.1185 0.2400 0.4209
16 16 16 16 var8 0.57779 0.77801 0.67238 0.42431 anti-osteopontin 0.0191 0.0004 0.0043 0.1014
16 16 16 16 var9 0.54194 0.51938 0.75615 0.72579 anti-Factor X/Xa 0.0301 0.0392 0.0007 0.0015
16 16 16 16 varlO 0.53467 0.51875 0.74441 0.62790 anti CD14 0.0329 0.0395 0.0009 0.0092
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations varδl var62 var63 var64
Capture 0.66731 0.74555 0.78627 0.52532
0.0047 0.0009 0.0003 0.0367
16 16 16 16 varl 0.74929 0.82864 0.90029 0.66836 anti-Fetuin A 0.0008 <.O001 <.0001 0.0047
16 16 16 16 var2 0.89920 0.78790 0.95060 0.97252 anti-calmodulin <.0001 0.0003 <.0001 <.0001
16 16 16 16 var3 0.84440 0.69336 0.90188 0.98407 anti-Tgase Il <.0001 0.0029 <.0001 <.0001
16 16 16 16 var4 0.86675 0.73329 0.92769 0.98742 anti-MMP-9 <.0001 0.0012 <.0001 <.0001
16 16 15 16 var5 0.39770 0.53435 0.51241 0.22030 anti-MMP-3 0.1271 0.0330 0.0424 0.4123
16 16 16 16 varδ 0.63590 0.80429 0.80973 0.50244 anti-CD 42b 0.0081 0.0002 0.0001 0.0473
16 16 16 16 var7 0.41933 0.33497 0.38471 0.39449 NF-kappa B 0.1059 0.2047 0.1412 0.1305
16 16 16 16 var8 0.63326 0.65936 0.68114 0.50997 anti-osteopontin 0.0085 0.0055 0.0037 0.0436
16 16 16 16 var9 0.8S002 0.71780 0.92693 0.98805 anti-Factor X/Xa <.0001 0.0017 <.0001 <.0001
16 16 16 16 varlO 0.86704 0.72304 0.91901 0.98909 anti CD14 <-0001 0.0016 <.0001 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var65 var66 varS7 var68
Capture 0.7567S 0.71633 0.42853 0.53166
0.0007 0.0018 0.0977 0.0340
16 16 16 16 varl 0.80573 0.84745 0.41157 0.54156 anti-Fetuin A 0.0002 <.0001 0.1132 0.0303
16 16 16 16 var2 0.84106 0.91876 0.S9364 0.68922 anti-calmodulin <.0001 <.0001 0.0153 0.0031
16 16 16 16 var3 0.78745 0.84891 0.61915 0.65043 anti-Tgase II 0.0003 <.0001 0.0105 0.0064
16 16 16 16 var4 0.817S3 0.88468 0.61710 0.66543 anti-MMP-9 0.0001 <.0001 0.0109 0.0049
16 16 16 16 var5 0.39117 0.47963 0.00427 0.25592 anti-MMP-3 0.1341 0.0601 0.9875 0.3387
16 16 16 16 var6 0.75314 0.77155 0.37975 0.42827 anti-CD 42b 0.0008 0.0005 0.1468 0.0979
16 16 16 16 var7 0.33425 0.38685 0.13357 0.13663 NF-kappa B 0.2058 0.1388 0.6219 0.6139
16 16 16 16 var8 0.60958 0.65038 0.22358 0.28187 anti-osteopontin 0.0122 0.0064 0.40B2 0.2902
16 16 16 16 var9 0.82108 0.87679 0.61173 0.68536 anti-Factor X/Xa <.0001 <.0001 0.0118 0.0034
16 16 16 16 varlO 0.81349 0.87627 0.62043 0.66200 anti CD14 0.0001 <.0001 0.0103 0.0052
16 16 16 16
Pearson Correlation Coefficients Prob > |r] under HO: Rho=0 Number of Observations var69 var70 var71 var72
Capture 0.02274 0.92490 0.90084 0.83004
0.9334 <.0001 <.0001 <.0001
16 16 16 16 varl 0.05661 0.93068 0.92293 0.90725 anti-Fetuin A 0.8350 <.0001 <.0001 <.0001
16 16 16 16 var2 -0.00684 0.64023 0.66398 0.89004 anti-calmodulin 0.9799 0.0076 0.0050 <.0001
16 16 16 16 var3 0.00385 0.58421 0.58842 0.84504 anti-Tgase II 0.9887 0.0175 0.0165 <.0001
16 16 16 16 var4 0.00753 0.60531 0.62415 0.85751 anti-MMP-9 0.9779 0.0130 0.0098 <.0001
16 16 16 16 varS -0.11547 0.54221 0.55053 0.63843 anti-MMP-3 0.6702 0.0300 0.0271 0.0078 ie 16 16 16 var6 0.10750 0.95539 0.947J.1 0.79704 anti-CD 42b 0.6919 <.0001 ■=.0001 0.0002
16 16 16 16 var7 0.08661 0.18542 0.19951 0.39437
NF-kappa B 0.7498 0.4918 0.4588 0.1306
16 16 16 16 var8 0.02999 0.63683 0.62878 0.71910 anti-osteopontin 0.9122 0.0080 0.0091 0.0017
IS 16 16 iε var9 0.02069 0.61494 0.63529 0.86242 anti-Factor X/Xa 0.9394 0.0112 0.0082 <.0001
16 16 16 16 varlO 0.00619 0.59467 0.61156 0.84872 anti CD14 0.9819 0.0151 0.0118 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RIiO=O Number of Observations var74 var75 var76 var77
Capture 0.91067 0.93923 0.93867 0.80153
<.0001 <.0001 <.0001 0.0002
16 16 16 16 varl 0.91469 0.94447 0.94841 0.74495 anti-Fetuin A <.0001 ■c.OOOl <.0001 0.0009
16 16 16 16 var2 0.52639 0.61580 0.61244 0.50938 anti-calmodulin 0.0362 0.0111 0.0117 0.0439
16 16 16 16 var3 0.43266 0.53344 0.53225 0.47936 anti-Tgase II 0.0942 0.0333 0.0338 0.0603
16 16 16 16 var4 0.46552 0.56283 0.56005 0.48453 anti-MMP-9 0.0692 0.0232 0.0241 0.0572
16 16 16 16 var5 0.70436 0.73158 0.73956 0.59036 anti-MMP-3 0.0023 0.0013 0.0011 0.0161
16 16 16 16 varδ 0.96401 0.86383 0.87890 0.79045 anti-CD 42b <.0001 <.0001 <.0001 0.0003
16 16 16 16 var7 0.17992 0.22001 0.22946 0.31338 NF-kappa B 0.5049 0.4129 0.3926 0.2372
16 16 16 16 var8 0.66374 0.65906 0.66896 0.69043 anti-osteopontin 0.0051 0.0055 0.0046 0.0031
16 16 16 16 var9 0.47162 0.61180 0.60457 0.46893 anti-Factor X/Xa 0.0651 0.0118 0.0131 0.0669
16 16 16 16 varlO 0.44842 0.55131 0.54822 0.47549 anti CD14 0.0815 0.0269 0.0279 0.0627
16 16 16 16 Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var78 var79 var80 varδl
Capture 0.52692 0.77586 0.92726 0.40299
0.0360 0.0004 <.0001 0.1721
16 16 16 13 varl 0.62008 0.81681 0.94615 0.40855 anti-Fetuin A 0.0104 0.0001 <.0001 0.1657
16 16 16 13 var2 0.84333 0.41588 0.60073 0.69511 anti-calmodulin <.0001 0.1091 0.0139 0.0084
16 16 16 13 var3 0.88376 0.31976 0.51284 0.77714 anti-Tgase II <.0001 0.2273 0.0422 0.0018
16 16 16 13 var4 0.85582 0.35929 0.54530 0.72543 anti-MMP-9 <.0001 0.1717 0.0289 0.0050
16 16 16 13 varS 0.49980 0.72880 0.71339 0.18341 anti-MMP-3 0.0487 0.0014 0.0019 0.5487
16 16 16 13 varβ 0.52267 0.88030 0.95302 0.39801 anti-CD 42b 0.0378 <.0001 <.0001 0.1780
16 16 16 13 var7 0.68430 0.13304 0.20478 0.32499 NF-kappa B 0.0035 0.6233 0.4468 0.2786
16 16 16 13 var8 0.81845 0.58860 0.67966 0.52456 anti-osteopontin 0.0001 0.0165 0.0038 0.0657
16 16 16 13 var9 0.79248 0.36059 0.56088 0.64036 anti-Factor X/Xa 0.0003 0.1700 0.0238 0.0184
16 16 16 13 varlO 0.85780 0.33502 0.52908 0.72315 anti CD14 <.0001 0.2046 0.0351 0.0052
16 16 16 13
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var82 var83 var84 var85
Capture 0.68495 0.93635 0.83437 0.96109
0.0098 <.0001 0.0004 <.0001
13 13 13 13 varl 0.77161 0.93032 0.78479 0.93519 anti-Fetuin A 0.0020 <.0001 0.0015 <.0001
13 13 13 13 var2 0 .61683 0 .79740 0 .73270 0 .58442 anti-calmodulin 0 . 0247 0 . 0011 0. 0044 0. 0359
13 13 13 13 var3 0 .53139 0 .73836 0 .70511 0 .50913 anti-Tgase II 0. 0616 0 . 0039 0. 0071 0. 0756
13 13 13 13 var4 0 .58096 0 .76321 0 .71362 0 .53623 anti-MMP-9 0.0373 0.0024 0.0062 0.0589
13 13 13 13 var5 0.52732 0.62196 0.41579 0.73554 anti-MMP-3 0.0640 0.0232 0.1576 0.0042
13 13 13 13 varβ 0.80693 0.77498 0.54191 0.87345 anti-CD 42b 0.0009 0.0019 0.0557 <.0001
13 13 13 13 var7 0.18374 0.28352 0.23791 0.22248 NF-kappa B 0.5479 0.3479 0.4338 0.4650
13 13 13 13 var8 0.50253 0.61969 0.47941 0.63289 anti-osteopontin 0.0801 0.0239 0.0974 0.0203
13 13 13 13 var9 0.58738 0.82489 0.80677 0.59061 anti-Factor X/Xa 0.0348 0.0005 0.0009 0.0336
13 13 13 13 varlO 0.55925 0.75638 0.72029 0.52326 anti CD14 0.0469 0.0028 0.0055 0.0665
13 13 13 13
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var86 var87 var88 var89
Capture 0.83523 0.73230 0.20993 0.65948
<-0001 0.0019 0.4527 0.0075
16 15 15 15 varl 0.80522 0.81257 0.19853 0.75658 anti-Fetuin A 0.0002 0.0002 0.4781 0.0011
16 15 15 15 var2 0.38817 0.47010 0.29036 0.91093 anti-calmodulin 0.1374 0.0770 0.2938 <.0001
16 15 15 15 var3 0.29482 0.39007 0.41067 0.89759 anti-Tgase II 0.2677 0.1506 0.1284 <.0001
16 15 15 15 var4 0.33832 0.43573 0.33465 0.90955 anti-MMP-9 0.1999 0.1045 0.2228 <.0001
16 15 15 15 var5 0.44373 0.42901 0.02229 0.33604 anti-MMP-3 0.0851 0.1106 0.9372 0.2207
16 15 15 15 var6 0.86399 0.79661 0.20360 0.52020 anti-CD 42b ■=.0001 0.0004 0.4667 0.0468
16 15 15 15 var7 0.03687 0.04733 -0.02347 0.35640 NF-kappa B 0.8922 0.8670 0.9338 0.1923
16 15 15 15 var8 0.46995 0.38155 0.24761 0.51022 anti-osteopontin 0.0662 0.1605 0.3736 0.0520
16 15 15 15 var9 0.37861 0.49897 0.26989 0.96468 anti-Factor X/Xa 0.1482 0.0583 0.3306 ■=.0001
16 15 15 15 varlO 0.32913 0.42311 0.33066 0.91407 anti CD14 0.2132 0.1161 0.2287 <.0001 16 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var90 var91 var92 var93
Capture 0.39089 0.75647 0.75787 0.49591
0.1497 0.0011 0.0007 0.0508
15 15 16 16 varl 0.56636 0.84200 0.79912 0.65320 anti-Fetuin A 0.0277 <.0001 0.0002 0.0061
15 15 16 16 var2 0.92862 0.96143 0.82839 0.97719 anti-calmodulin <.0001 <.0001 <.0001 <.0001
15 15 16 16 var3 0.92091 0.91769 0.82862 0.97947 anti-Tgase II <.0001 <.0001 <.0001 <.0001
15 15 16 16 var4 0.93604 0.93836 0.82857 0.98817 anti-MMP-9 <.0001 <.0001 <.0001 <.0001
15 15 16 16 var5 0.33069 0.44561 0.39380 0.24174 anti-MMP-3 0.2286 0.0960 0.1312 0.3671
15 15 16 16 var6 0.41406 0.71031 0.57954 0.50233 anti-CD 42b 0.1249 0.0030 0.0186 0.0474
15 15 16 16 var7 0.65986 0.44826 0.29249 0.45812
NF-kappa B 0.0074 0.0938 0.2716 0.0743
15 15 16 16 var8 0.62900 0.68505 0.53943 0.54033 anti-osteopontin 0.0120 0.0048 0.0310 0.0307
15 15 16 16 var9 0.91107 0.94536 0.89165 0.97842 anti-Factor X/Xa <.0001 <.0001 <.0001 <.0001
15 15 16 16 varlO 0.93905 0.93775 0.83272 0.98963 anti CD14 <.0001 <.0001 <.0001 <.0001
15 15 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations
Capture varl var2 var3 varll 0.70832 0.63724 0.22354 0.11153 anti-prothrombin 0.0021 0.0079 0.4053 0.6809
16 16 16 16 varl2 0.57671 0.71641 0.98449 0.98157 anti-Factor IX 0.0194 0.0018 <.0001 <.0001
16 16 16 16 varl3 0.88442 0.96367 0.89303 0.84782 anti-Fetuin B <.0001 <.0001 <.0001 <.0001
16 16 16 16 varl4 0.05923 0.15111 0.23225 0.20211 anti-CD40 0.8275 0.5764 0.3867 0.4529
16 16 16 16 varl5 0.28195 0.34949 0.41062 0.35023 anti-myeloperoxidase 0.2901 0.1845 0.1141 0.1836
16 16 16 16 varl6 0.51899 0.61993 0.92951 0.94957 vanti-Fibronectin 0.0394 0.0104 <.0001 <.0001
16 16 16 16 varl7 0.67705 0.79587 0.98452 0.97122 anti-Factor VII 0.0040 0.0002 ■c.OOOl <.0001
16 16 16 16 varl8 0.64129 0.76742 0.98947 0.98767 anti-tissue factor 0.0074 0.0005 <.0001 <.0001 ie 16 16 16 varl9 0.49770 0.65791 0.97407 0.95984 anti-human complement 5b-9 0.0498 0.0056 <.0001 <.0001
16 16 16 16 var20 0.47936 0.60423 0.91784 0.96775 anti-human CRP 0.0603 0.0132 <.0001 <.0001
16 16 16 16 var21 0.88105 0.93081 0.67281 0.58348 anti-rαatrix GLA <.0001 <.0001 0.0043 0.0177
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var4 var5 var6 var7 varll 0.14631 0.69878 0.55757 0.01608 anti-prothrombin 0.5887 0.0026 0.0248 0.9529
16 16 16 16 varl2 0.99094 0.29848 0.54529 0.42396 anti-Factor IX <.0001 0.2615 0.0289 0.1017
16 16 16 16 varl3 0.86772 0.52688 0.86044 0.34154 anti-Fetuin B <.0001 0.0360 <.0001 0.1954
16 16 16 16 varl4 0.20835 0.63685 0.13309 0.94828 anti-CD40 0.4387 0.0080 0.6232 <.0001
16 16 16 16 varlS 0.36891 0.80332 0.32601 0.90119 anti-myeloperoxidase 0.1597 0.0002 0.2179 <.0001
16 16 16 16 varlδ 0.94567 0.30536 0.47516 0.47331 vanti-Fibronectin <.0001 0.2501 0.0629 0.0641
16 16 16 16 varl7 0.97960 0.44636 0.61878 0.48916 anti-Factor VII <.0001 0.0831 0.0106 0.0545
16 16 16 16 varl8 0.99139 0.38813 0.61754 0.42528 anti-tissue factor <.0001 0.1374 0.0108 0.1006
16 16 16 16 varl9 0.97578 0.29682 0.51326 0.53231 anti-human complement 5b-9 <.0001 0.2643 0.0420 0.0338
16 16 16 16 var20 0.94614 0.17637 0.49394 0.34426 anti-human CRP <.0001 0.5135 0.0518 0.1917
16 16 16 16 var21 0.61876 0.61698 0.98125 0.23612 anti-matrix GLA 0.0106 0.0109 <-0001 0.3786 ie 16 ie 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var8 var9 varlO varll varll 0.42121 0.20805 0.13315 1.00000 anti-prothrombin 0.1042 0.4394 0.6230
16 16 16 16 varl2 0.5S314 0.99729 0.99154 0.15400 anti-Factor IX 0.0262 <.0001 <-0001 0.5691
16 16 16 16 varl3 0.68982 0.89231 0.86294 0.49017 anti-Fetuin B 0.0031 <.0001 <.0001 0.0539
16 16 16 16 varl4 0.74645 0.13080 0.21406 0.04468 anti-CD40 0.0009 0.6292 0.4260 0.8695
16 16 16 16 varl5 0.81846 0.29691 0.36585 0.26620 anti-myeloperoxidase 0.0001 0.2641 0.1635 0.3190
16 16 16 16 varl6 0.59266 0.92467 0.94549 0.10198 vanti-Fibronectin 0.0155 <.0001 <.0001 0.7070
16 16 16 16 varl7 0.66521 0.98883 0.97991 0.29676 anti-Factor VII 0.0049 <.0001 <.0001 0.2644
16 16 16 16 varl8 0.62493 0.98468 0.98848 0.24073 anti-tissue factor 0.0096 <.0001 <.0001 0.3691
16 16 16 16 varl9 0.59215 0.96146 0.97778 0.07752 anti-human complement 5b-9 0.0157 <-0001 <.0001 0.7754
16 16 16 16 var20 0.51585 0.91038 0.94551 -0.00345 anti-human CRP 0.0408 <.0001 <.0001 0.9899
16 16 16 16 var21 0.68745 0.60706 0.60270 0.60155 anti-matrix GLA 0.0033 0.0126 0.0135 0.0137
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations varl2 varl3 varl4 varl5 varll 0.15400 0.49017 0.04468 0.26620 anti-prothrombin 0.5691 0.0539 0.8695 0.3190
16 16 16 16 varl2 1.00000 0.86912 0.13767 0.29887 anti-Factor IX <.0001 0.6111 0.2608
16 16 16 16 varl3 0.86912 1.00000 0.11729 0.32196 anti-Fetuin B <-0001 0.6653 0.2240
16 16 16 16 varl4 0.13767 0.11729 1.00000 0.90962 anti-CD40 0.6111 0.6653 <.0001 16 16 16 16 varl5 0.29887 0.32196 0.90962 1.00000 anti-myeloperoxidase 0.2608 0.2240 <.0001
16 16 16 16 varl6 0.93094 0.78148 0.21579 0.36323 vanti-Fibronectin <.0001 0.0004 0.4222 0.1667
16 16 16 16 varl7 0.98139 0.91466 0.22709 0.40116 anti-Factor VII <.0001 <.0001 0.3977 0.1236
16 16 16 16 varl8 0.98447 0.89730 0.15507 0.34192 anti-tissue factor <.0001 <.0001 0.5663 0.1949
16 16 16 16 varl9 0.97340 0.81081 0.26937 0.39480 anti-human complement 5b~9 <.0001 0.0001 0.3130 0.1302
IS 16 16 16 var20 0.92313 0.76474 0.07706 0.20469 anti-human CRP <.0001 0.0006 0.7767 0.4470
IS IS IS IS var21 0.58712 0.86712 0.12158 0.34046 anti-matrix GLA 0.0168 <.0001 0.6538 0.1969
16 IS 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations varl6 varl7 varl8 varl9 varll 0.10198 0.29676 0.24073 0.07752 anti-prothrombin 0.7070 0.2644 0.3691 0.7754
16 16 16 16 varl2 0.93094 0.98139 0.98447 0.97340 anti-Factor IX <.0001 <.0001 <.0001 <.0001
16 16 16 16 varl3 0.78148 0.91466 0.89730 0.81081 anti-Fetuin B 0.0004 <.0001 <.0001 0.0001
16 16 16 16 varl4 0.21579 0.22709 0.15507 0.26937 anti-CD40 0.4222 0.3977 0.5663 0.3130
16 16 16 16 varl5 0.36323 0.40116 0.34192 0.39480 anti-myeloperoxidase 0.1667 0.1236 0.1949 0.1302
16 16 16 16 varl6 1.00000 0.91890 0.93681 0.90876 vanti-Fibronectin <.0001 <.0001 <.0001
16 16 16 16 varl7 0.91890 1.00000 0.98544 0.94721 anti-Factor VII <.0001 <.0001 <.0001
16 16 16 16 varl8 0.93681 0.98544 1.00000 0.94518 anti-tissue factor <.0001 <.0001 <.0001
16 16 16 16 varl 9 0.90876 0.94721 0.94518 1.00000 anti-human complement 5b-9 <.0001 <.0001 <.0001
16 16 16 16 var20 0.91937 0.89281 0.94476 0.88332 ant i- human CRP <.0001 ■=.0001 <.0001 <.0001
16 16 16 16 var21 0.51007 0.65116 0.65549 0.56744 anti-matrix GLA 0.0435 0.0063 0.0058 0.0219
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var20 var21 var22 var23 varll 0.00345 0.60155 0.15682 0.26293 anti-prothrombin 0.9899 0.0137 0.5619 0.3252
16 16 16 16 varl2 0.92313 0.58712 0.36071 0.43977 anti-Factor IX <.0001 0.0168 0.1699 0.0883
16 16 16 16 varl3 0.76474 0.86712 0.31378 0.46081 anti-Fetuin B 0.0006 <.0001 0.2366 0.0724
16 16 16 16 varl4 0.07706 0.12158 0.16735 0.87312 anti-CD40 0.77S7 0.6538 0.5356 <.0001
16 16 16 16 varlδ 0.20469 0.34046 0.37312 0.91216 anti-myeloperoxidase 0.4470 0.1969 0.1546 <.0001
16 16 16 16 varl6 0.91937 0.51007 0.33273 0.45662 vanti-Fibronectin <.0001 0.0435 0.2079 0.0754
16 16 16 16 varl7 0.89281 0.65116 0.39401 0.54324 anti-Factor VII <.0001 0.0063 0.1310 0.0297
16 16 16 16 varl8 0.94476 0.65549 0.37584 0.46279 anti-tissue factor <.0001 0.0058 0.1514 0.0711
16 16 16 16 varl9 0.88332 0.56744 0.38078 0.52607 anti-human complement 5b-9 <.0001 0.0219 0.1457 0.0363
16 16 16 16 var20 1.00000 0.51003 0.30351 0.32727 anti-human CRP 0.0436 0.2531 0.2160
16 16 16 16 var21 0.51003 1.00000 0.29536 0.40286 anti-matrix GLA 0.0436 0.2667 0.1218
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var24 var25 var26 var27 varll 0.12901 0.18856 0.29769 0.13348 anti-prothrombin 0.6340 0.4843 0.2628 0.6221
16 16 16 16 varl2 0.88227 0.97522 0.96218 0.98860 anti-Factor IX <.0001 <.0001 <.0001 <.0001
16 16 16 16 varl3 0.73338 0.87530 0.90334 0.86957 anti-Fetuin B 0.0012 <.0001 <.0001 <.0001
16 16 16 16 varl4 0.17368 0.25680 0.29098 0.19812 anti-CD40 0.5200 0.3370 0.2742 0.4620
16 16 IS 16 varl5 0.37979 0.41191 0.46862 0.35540 anti-myeloperoxidase 0.1468 0.1129 0.0671 0.1767
16 16 16 16 varl6 0.79898 0.93930 0.90979 0.94775 vanti-Fibronectin 0.0002 •=.0001 <.0001 <.0001
16 16 16 16 varl7 0.87614 0.97890 0.98003 0.97691 anti-Factor VII <.O001 <.0001 <.0001 <.0001
16 16 16 16 var!8 0.88430 0.99054 0.97832 0.99207 anti-tissue factor <.0001 <.0001 <.0001 <.0001
16 16 16 16 varl9 0.87265 0.95941 0.95390 0.96645 anti-human complement 5b-9 <.0001 <.0001 <.0001 <.0001
16 16 16 16 var20 0.83034 0.94827 0.89075 0.95630 anti-human CRP <.0001 <.0001 <.0001 <.0001
16 16 16 16 var21 0.51509 0.64331 0.70702 0.61519 anti-matrix GLA 0.0412 0.0072 0.0022 0.0112
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var28 var29 var30 var31 varll 0.82693 0.79726 0.15830 0.26228 anti-prothrombin <.0001 0.0002 0.5582 0.3264
16 16 16 16 varl2 0.08805 0.10882 0.37052 0.31991 anti-Factor IX 0.7457 0.6883 0.1577 0.2271
16 16 16 16 varl3 0.37279 0.38861 0.37669 0.38391 anti-Fetuin B 0.1550 0.1369 0.1504 0.1421
16 16 16 16 varl4 0.52514 0.00164 0.95814 0.93780 anti-CD40 0.0367 0.9952 <.0001 <.0001
16 16 16 16 varlS 0.67260 0.13611 0.92988 0.92070 anti-myeloperoxidase 0.0043 0.6152 <.0001 <.0001
16 16 16 16 varl6 0.07964 0.06183 0.42521 0.37951 vanti-Fibronectin 0.7694 0.8200 0.1006 0.1471
16 16 16 16 varl7 0.23914 0.24512 0.46595 0.43651 anti-Factor VII 0.3724 0.3602 0.0689 0.0909
16 16 16 16 varl8 0.17162 0.15208 0.39338 0.36798 anti-tissue factor 0.5251 0.5739 0.1317 0.1608
16 16 16 16 varl9 0.12142 -0.03540 0.46982 0.40176 anti-human complement 5b-9 0.6542 0.8964 0.0663 0.1229
16 16 16 16 var20 -0.07436 -0.07019 0.28790 0.26105 anti-human CRP 0.7843 0.7962 0.2796 0.3288 16 16 16 16 var21 0.5B061 0.28654 0.33086 0.37979 anti-matrix GLA 0.0184 0.2819 0.2107 0.1468
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var32 var33 var34 var35 varll 0.32157 0.27248 0.22301 -0.13829 anti-prothrombin 0.2245 0.3073 0.4064 0.6095
16 IS 16 16 varl2 -0.13910 0.98495 0.93321 0.63897 anti-Factor IX 0.6074 ■=.0001 <.0001 0.0077
16 16 16 16 varl3 -0.07111 0.90296 0.83381 0.39639 anti-Fetuin B 0.7936 <.0001 <.0001 0.1285
16 16 16 16 varl4 0.40537 0.12098 0.13351 -0.00392 anti-CD40 0.1193 0.6554 0.6220 0.9885
16 16 16 16 varl5 0.34295 0.29782 0.29197 0.00390 anti-myeloperoxidase 0.1935 0.2626 0.2725 0.9886
16 16 16 16 varl6 -0.23721 0.91899 0.86813 0.53005 vanti-Fibronectin 0.3764 <.0001 <.0001 0.0347
16 16 16 16 varl7 -0.08381 0.99141 0.91958 0.56212 anti-Factor VII 0.7576 <.0001 <.0001 0.0234
16 16 16 16 varl8 -0.11789 0.98356 0.92746 0.57768 anti-tissue factor 0.6637 <.0001 <.0001 0.0191
16 16 16 16 varl9 -0.05027 0.92935 0.95168 0.65004 anti-human complement 5b-9 0.8533 <.0001 <.0001 0.0064
16 16 16 16 var20 -0.24971 0.90342 0.86670 0.58044 anti-human CRP 0.3510 <.0001 <.0001 0.0184
16 .16 16 16 var21 0.14430 0.60755 0.65640 0.14383 anti-matrix GLA 0.5939 0.0125 0.0057 0.5951
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var36 var37 var38 var39 varll 0.07474 0.30097 0.42187 0.16455 anti-prothrombin 0.7833 0.2573 0.1036 0.5425
16 16 16 16 varl2 0.98050 0.96202 0.45428 0.99792 anti-Factor IX <.0001 <.0001 0.0771 <.0001
16 16 16 16 varl3 0.81799 0.90874 0.52545 0.87162 anti-Fetuin B 0.0001 <.0001 0.0366 <.0001
16 16 16 16 varl4 0.23153 0.15683 0.00683 0.13734 anti-CD40 0.3882 0.5619 0.9800 0.6120
16 16 16 16 varl5 0.36299 0.34273 0.27770 0.29281 anti-myeloperoxidase 0.1S70 0.1938 0.2977 0.2711
16 16 16 16 varl6 0.91241 0.92033 0.39490 0.93118 vanti-Fibronectin <.0001 <.0001 0.1301 <.0001
16 16 16 16 varl7 0.95236 0.98065 0.45461 0.98502 anti-Factor VII ■=.0001 <-0001 0.0769 <.0001
16 16 16 16 varlδ 0.95380 0.99114 0.51036 0.98262 anti-tissue factor <.0001 <.0001 0.0434 <,0001
16 16 16 16 varl9 0.99820 0.91303 0.41354 0.96490 anti-human complement 5b-9 <.0001 <.0001 0.1113 <.0001
16 16 16 16 var20 0.89933 0.93873 0.37579 0.92196 anti-human CRP <.0001 <.0001 0.1514 <.0001
16 16 16 16 var21 0.56697 0.67566 0.62267 0.57268 anti-matrix GLA 0.0220 0.0041 0.0100 0.0204
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var40 var41 var42 var43 varll 0.60398 0.48652 0.08540 -0.01204 anti-prothrombin 0.0132 0.0560 0.7532 0.9647
16 16 IS 16 varl2 0.76375 0.81505 0.90646 0.94230 anti-Factor IX 0.0006 0.0001 <.0001 <.0001
16 16 16 16 varl3 0.85893 0.98466 0.77665 0.74645 anti-Fetuin B <.0001 <.0O01 0.0004 0.0009
16 16 16 16 varl4 0.02003 0.12320 0.07917 0.11691 anti-CD40 0.9413 0.6494 0.7707 0.6663
16 16 16 16 varl5 0.27707 0.33588 0.20781 0.27490 anti-myeloperoxidase 0.2989 0.2034 0.4399 0.3028
16 16 16 16 varl6 0.66993 0.73280 0.79247 0.86661 vanti-Fibronectin 0.0045 0.0012 0.0003 <.0001
16 16 16 16 varl7 0.80773 0.86068 0.88242 0.90233 anti-Factor VII 0.0002 <.0001 <.0001 <.0001
16 16 16 16 varl8 0.79686 0.85753 0.86085 0.90742 anti-tissue factor 0.0002 <.0001 <.0001 <.0001
16 16 16 16 varl9 0.66042 0.76957 0.88585 0.94065 anti-human complement 5b-9 0.0054 0.0005 <.0001 <.0001
16 16 16 16 var20 0.61439 0.73685 0.78852 0.87232 anti-human CRP 0.0113 0.0011 0.0003 <-0001 16 IS 16 16 var21 0. 70797 0.92621 0. 47473 0.46987 anti-matrix GLA 0.0021 <.0001 0.0632 0.0663 16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var45 var46 var47 var48 varll -0.16726 0.22172 0.43601 0.75698 anti-prothrombin 0.5358 0.4092 0.0914 0.0007
16 16 16 16 varl2 0.33641 0.138S3 0.75109 0.34627 anti-Factor IX 0.2027 0.6086 0.0008 0.1889
16 16 16 16 varl3 0.22438 0.20930 0.74007 0.71016 anti-Fetuin B 0.4035 0.4366 0.0010 0.0021
16 16 16 16 varl4 -0.06278 0.91176 -0.00820 0.03253 anti-CD40 0.8173 <.0001 0.9759 0.9048
16 16 16 16 varl5 -0.21443 0.87709 0.25678 0.23233 anti-myeloperoxidase 0.4252 <.0001 0.3370 0.3866
16 16 16 16 varl6 0.23453 0.30727 0.63315 0.26150 vanti-Fibronectin 0.3819 0.2470 0.0085 0.3279
16 16 16 16 varl7 0.27476 0.24720 0.74875 0.43840 anti-Factor VII 0.3031 0.3560 0.0008 0.0894
16 16 16 16 varl8 0.28198 0.18215 0.77357 0.42833 anti-tissue factor 0.2900 0.4996 0.0004 0.0979
16 16 16 16 varl9 0.35948 0.22513 0.72003 0.28133 anti-human complement 5b-9 0.1715 0.4018 0.0017 0.2912
16 16 16 16 var20 0.30347 0.07759 0.64043 0.23912 anti-human CRP 0.2532 0.7752 0.0075 0.3724
16 16 16 16 var21 0.14157 0.24338 0.67953 0.89086 anti-matrix GIA 0.6010 0.3637 0.0038 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var49 var50 varSl var52 varll 0.74985 0.51525 0.16622 0.22668 anti-prothrombin 0.0008 0.0411 0.5384 0.3985
16 16 16 16 varl2 0.45538 0.78830 0.86583 0.95919 anti-Factor IX 0.0763 0.0003 <.0001 <.0001
16 16 16 16 varl3 0.81796 0.82512 0.77849 0.87891 anti-Fetuin B 0.0001 <.0001 0.0004 <.0001
IS 16 16 16 varl4 0.00259 0.06330 0.33714 0.10145 anti-CD40 0.9924 0.8158 0.2016 0.7085
16 16 16 16 varl5 0.23144 0.21895 0.49767 0.28965 anti-myeloperoxidase 0.3884 0.4152 0.0498 0.2765
16 16 16 16 varlS 0.36389 0.69980 0.89864 0.92978 vanti-Fibronectin 0.1659 0.0025 <.0001 <.0001
16 16 16 16 varl7 0.54486 0.84959 0.90391 0.95897 anti-Factor VII 0.0291 <.O001 <.0001 ■c.OOOl
16 16 16 16 varl8 0.51891 0.78341 0.89368 0.98978 anti-tissue factor 0.0394 0.0003 <.0001 <.0001
16 16 16 16 varl9 0.39417 0.68151 0.82222 0.89904 anti-human complement 5b-9 0.1309 0.0036 <.0001 <.0001
16 16 16 16 var20 0.32529 0.62551 0.86467 0.96273 anti-human CRP 0.2189 0.0096 <.0001 <.0001
16 16 16 16 var21 0.93764 0.49789 0.49407 0.64028 anti-matrix GIA <.0001 0.0497 0.0517 0.0075
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var53 var54 var55 var56 varll -0.00729 0.51270 0.66477 0.44546 anti-prothrombin 0.9786 0.0423 0.0050 0.0838
16 16 16 16 varl2 0.89977 0.11732 0.62440 0.83955 anti-Factor IX <.0001 0.6652 0.0097 <.0001
16 16 16 16 varl3 0.73528 0.31116 0.75163 0.84071 anti-Fetuin B 0.0012 0.2408 0.0008 <.0001
16 16 16 16 varl4 0.45892 -0.10351 -0.02055 0.05527 anti-CD40 0.0738 0.7028 0.9398 0.8389
16 16 16 16 varlS 0.53804 -0.03914 0.25511 0.21003 anti-myeloperoxidase 0.0316 0.8856 0.3403 0.4349
16 16 16 16 varl6 0.91169 0.16219 0.52854 0.74659 vanti-Fibronectin <.0001 0.5484 0.0353 0.0009
16 16 16 16 varl7 0.89930 0.23649 0.67429 0.88291 anti-Factor VII <.0001 0.3779 0.0042 <.0001
16 16 16 16 varlδ 0.91148 0.20430 0.66347 0.82448 anti-tissue factor <.0001 0.4479 0.0051 <.0001
16 16 16 16 varl9 0.91950 -0.06604 0.51565 0.74048 anti-human complement 5b-9 <.0001 0.8080 0.0409 0.0010 is 16 16 IS var20 0.91554 0.18158 0.45481 0.67681 anti-human CRP <.0001 0.5009 0.0767 0.0040
IS 16 16 16 var21 0.49335 0.13307 0.65958 0.49753 anti-matrix GLA 0.0521 0.6232 0.0054 0.0499
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var57 var58 var59 var60 varll 0.62708 0.61759 0.67062 0.55119 anti-prothrombin 0.0093 0.0108 0.0045 0.0269
16 16 16 16 varl2 0.52562 0.48868 0.73594 0.67821 anti-Factor IX 0.0365 0.0548 0.0012 0.0039
16 16 16 16 varl3 0.76332 0.77498 0.85378 0.75491 anti-Fetuin B O.OOOS 0.0004 <.0001 0.0007
16 16 16 16 varl4 0.06398 0.32614 0.17704 0.02053 anti-CD40 0.8139 0.2177 0.5119 0.9399
16 16 16 16 varl5 0.34104 0.56383 0.40781 0.16203 anti-myeloperoxidase 0.1961 0.0229 0.1169 0.5488
16 16 16 16 variε 0.45311 0.47465 0.66951 0.59197 vanti-Fibronectin 0.0780 0.0632 0.0046 0.0157
16 16 16 16 varl7 0.57520 0.59516 0.80243 0.75149 anti-Factor VII 0.0197 0.0150 0.0002 0.0008
16 16 16 16 varl8 0.58563 0.57377 0.78448 0.67462 anti-tissue factor 0.0171 0.0201 0.0003 0.0041
16 16 16 16 varl9 0.52259 0.44263 0.73373 0.55135 anti-human complement 5b-9 0.0378 0.0860 0.0012 0.0268
16 16 16 16 var20 0.41117 0.40976 0.61897 0.50703 anti-human CRP 0.1136 0.1150 0.0106 0.0450
16 16 16 16 var21 0.93372 0.84607 0.84044 0.43133 anti-matrix GIiA <.0001 <.0001 <-0001 0.0953
16 16 16 16
Pearson Correlation Coefficients Prob > |r] under HO: Rho=0 Number of Observations var61 var62 var63 var64 varll 0.38848 0.55262 0.41270 0.07530 anti-prothrombin 0.1370 0.0264 0.1121 0.7817
16 16 16 16 varl2 0.85565 0.70974 0.91899 0.99501 anti-Factor IX <.0001 0.0021 <.0001 <.0001
16 16 16 16 varl3 0.825S5 0.82780 0.96728 0.83476 anti-Fetuin B <-0001 <.0001 <.0001 <.0001
16 16 16 16 varl4 0.23724 0.20422 0.14700 0.10338 anti-CD40 0.37S3 0.4481 0.5870 0.7032
16 16 16 16 varl5 0.40091 0.41789 0.37340 0.24730 anti-myeloperoxidase 0.1238 0.1072 0.1543 0.3558
16 16 16 IS varl6 0.78682 0.64443 0.83962 0.93208 vanti-Fibronectin 0.0003 0.0070 <.0001 <.0001
16 16 16 16 varl7 0.87694 0.75035 0.93913 0.96279 anti-Factor VII <.0001 0.0008 <.0001 <.0001
16 16 16 16 varl8 0.85881 0.74488 0.94442 0.97633 anti-tissue factor <.0001 0.0009 <.0001 <.0001
16 IS 16 16 varl9 0.89284 0.74650 0.88991 0.96930 anti-human complement 5b- <.0001 0.0009 <.0001 <.0001
16 16 16 16 var20 0.74284 0.59106 0.82516 0.94536 anti-human CRP 0.0010 0.0159 <.0001 <.0001
16 16 16 16 var21 0.70785 0.87662 0.85304 0.54132 anti-matrix GLA 0.0022 <.0001 <.0001 0.0303
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var65 var66 var67 var68 varll 0.32148 0.41788 -0.12295 0.28796 anti-prothrombin 0.2247 0.1073 0.6501 0.2795
16 16 16 16 varl2 0.81185 0.87477 0.61679 0.68076 anti-Factor IX 0.0001 <.0001 0.0109 0.0037
16 16 16 16 varl3 0.86723 0.90574 0.54280 0.63080 anti-Fetuin B <.0001 <.0001 0.0298 0.0088
16 16 16 16 varl4 0.13009 0.17852 -0.07247 -0.04889 anti-CD40 0.6311 0.5083 0.7897 0.8573
16 16 16 16 varl5 0.28841 0.39021 0.13983 0.25971 anti-myeloperoxidase 0.2787 0.1351 0.6055 0.3314
16 16 16 16 varl6 0.72328 0.78802 0.53706 0.512S0 vanti-Fibronectin 0.0015 0.0003 0.0319 0.0423
16 16 16 16 varl7 0.82242 0.88724 0.57283 0.68478 anti-Factor VII <.0001 <-0001 0.0204 0.0034
16 16 16 16 varl8 0.81097 0.88911 0.59441 0.68035 anti-tissue factor 0.0001 <.0001 0.0152 0.0037
16 16 16 16 varl9 0.81231 0.88985 0.57943 0.63805 anti-human complement 5b-9 0.0001 <.0001 0.0187 0.0078
16 16 16 16 var20 0.S9255 0.75683 0.59244 0.56903 anti-human CRP 0.0029 0.0007 0.0156 0.0214
16 16 16 16 var21 0.80335 0.83926 0.36744 0.47412 anti-matrix GlA 0.0002 <.0001 0.1615 0.0635
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var69 var70 var71 var72 varll -0.14467 0.52735 0.53343 0.56131 anti-prothrombin 0.5929 0.0358 0.0333 0.0237
16 16 16 16 varl2 0.02136 0.58554 0.60999 0.84298 anti-Factor IX 0.9374 0.0172 0.0121 <.0001
16 16 16 16 varl3 0.05276 0.88222 0.88359 0.93997 anti-Fetuin B 0.8461 <.0001 <.0001 <.0001
16 16 16 16 varl4 -0.12048 0.04499 0.05231 0.19567 anti-CD40 0.6567 0.8686 0.8474 0.4677
16 16 16 16 varl5 -0.30785 0.27441 0.28576 0.44217 anti-myeloperoxidase 0.2461 0.3037 0.2833 0.0864
16 16 16 16 varlδ -0.04334 0.50985 0.52495 0.77323 vanti-Fibroneσtin 0.8734 0.0436 0.0368 0.0004
16 16 16 16 varl7 -0.00357 0.64988 0.66178 0.91075 anti-Factor VII 0.9895 0.0064 0.0052 <.0001
16 16 16 16 varlδ -0.01090 0.64786 0.65806 0.89750 anti-tissue factor 0.9680 0.0067 0.0056 <.0001
16 16 16 16 varl9 0.02177 0.51604 0.56163 0.78679 anti-human complement 5b-9 0.9362 0.0407 0.0236 0.0003
16 16 16 16 var20 0.02165 0.52308 0.50688 0.76413 anti-human CRP 0.9366 0.0376 0.0451 0.0006
16 16 16 16 var21 0.10728 0.92718 0.95053 0.81840 anti-matrix GLA 0.6925 <.0001 <.0001 0.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var74 var75 var76 var77 varll 0.73061 0.80934 0.79478 0.42272 anti-prothrombin 0.0013 0.0001 0.0002 0.1028
16 16 16 16 varl2 0.43762 0.56604 0.55961 0.44101 anti-Factor IX 0.0900 0.0223 0.0242 0.0873 is 16 16 16 varl3 0.80426 0.87246 0-87311 0.69810 anti-Fetuin B 0.0002 <.0001 <-0001 0.0026
16 16 16 16 varl4 0.11001 0.10048 0.11127 0.22494 anti-CD40 0.6851 0.7112 0.6816 0.4023
16 16 16 16 varl5 0.34622 0.34367 0.35154 0.36223 anti-myeloperoxidase 0.1890 0.1925 0.1818 0.1680
16 16 16 16 varlδ 0.36799 0.48110 0.47763 0.43650 vanti-Fibronectin 0.1608 0.0592 0.0613 0.0909
16 16 16 16 varl7 0.53769 0.67662 0.67179 0.52593 anti-Factor VII 0.0317 0.0040 0.0044 0.0364
16 16 16 16 varl8 0.52524 0.63523 0.63172 0.51696 anti-tissue factor 0.0367 0.0082 0.0087 0.0403
16 16 16 16 varl9 0.38440 0.47099 0.46544 0.38149 anti-human complement 5b-9 0.1415 0.0656 0.0692 0.1448
16 16 16 16 var20 0.35149 0.42577 0.42849 0.42877 anti-human CRP 0.1819 0.1001 0.0977 0.0975
16 16 16 16 var21 0.95978 0.86533 0.87340 0.75787 anti-matrix GIA <.0001 <.0001 <.0001 0.0007
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var78 var79 var80 var81 varll 0.11622 0.71412 0.73756 -0.06200 anti-prothrombin 0.6682 0.0019 0.0011 0.8405
16 16 16 13 varl2 0.79527 0.33210 0.52599 0.65660 anti-Factor IX 0.0002 0.2089 0.0364 0.0148
16 16 16 13 varl3 0.71497 0.69272 0.85821 0.52857 anti-Fetuin B 0.0019 0.0029 <.0001 0.0633
16 16 16 13 varl4 0.50326 0.07602 0.10254 0.15805 anti-CD40 0.0469 0.7796 0.7055 0.6061
16 16 16 13 varl5 0.59035 0.30459 0.35054 0.29365 anti-myeloperoxidase 0.0161 0.2514 0.1831 0.3302
16 16 16 13 varl6 0.85528 0.27119 0.44790 0.79691 vanti-Fibronectin <.0001 0.3096 0.0819 0.0011
16 16 16 13 varl7 0.84006 0.42274 0.62217 0.65764 anti-Factor VII <.0001 0.1028 0.0101 0.0146
16 16 16 13 varl8 0.85031 0.42984 0.60672 0.73338 anti-tissue factor <.0001 0.0966 0.0127 0.0043
16 16 16 13 varl9 0.78820 0.2S669 0.46019 0.61900 anti-human complement 5b-9 0.0003 0.3181 0.0729 0.0241
16 16 16 13 var20 0.867S2 0.26034 0.42630 0.86955 anti-human CRP <.0001 0.3301 0.0996 0.0001
16 16 16 13 var21 0.50976 0.89180 0.95676 0.38922 anti-matrix GLA 0.0437 <-0001 <.0001 0.1887
16 16 16 13
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var82 var83 var84 var85 varll 0.48047 0.74094 0.62320 0.84541 anti-prothrombin 0.0965 0.0038 0.0229 0.0003
13 13 13 13 varl2 0.58147 0.78973 0.76447 0.54763 anti-Factor IX 0.0371 0.0013 0.0023 0.0527
13 13 13 13 varl3 0.74321 0.93526 0.83087 0.85037 anti-Petuin B 0.0036 <.0001 0.0004 0.0002
13 13 13 13 varl4 0.01497 0.06883 0.02500 0.08346 anti-CD40 0.9613 0.8232 0.9354 0.7863
13 13 13 13 varl5 0.18582 0.31994 0.20383 0.32036 anti-myeloperoxidase 0.5433 0.2866 0.5042 0.2859
13 13 13 13 varlδ 0.47235 0.69515 0.67323 0.46406 vanti-Fibronectin 0.1031 0.0083 0.0117 0.1102
13 13 13 13 varl7 0.59570 0.86010 0.82954 0.65197 anti-Factor VII 0.0317 0.0002 0.0005 0.0157
13 13 13 13 varl8 0.61132 0.82209 0.75999 0.61289 anti-tissue factor 0.0264 0.0006 0.0026 0.0259
13 13 13 13 varl9 0.54441 0.68372 0.65436 0.43053 anti-human complement 5b-9 0.0544 0.0100 0.0152 0.1420
13 13 13 13 var20 0.47022 0.63508 0.59523 0.41630 anti-human CRP 0.1049 0.0197 0.0319 0.1571
13 13 13 13 var21 0.88600 0.81126 0.55610 0.87178 anti-matrix GLA <.0001 0.0008 0.0484 0.0001
13 13 13 13
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var86 var87 var88 var89 varll 0 .56056 0 .44995 -0 .04510 0 .30534 anti-prothrombin 0.0239 0.0924 0.8732 0.2684
16 15 15 15 varl2 0 .34180 0 .46955 0 .27249 0 .94643 anti-Factor Ix 0.1951 0.0774 0.3258 <.0001
16 15 15 15 varl3 0.70S10 0.76052 0.24316 0.88401 anti-Fetuin B 0.0022 0.0010 0.3825 <.0001
16 15 15 15 varl4 0.03169 -0.11296 -0.10412 0.07838 anti-CD40 0.9073 0.6885 0.7119 0.7813
16 15 15 15 varl5 0.10780 0.05410 -0.06559 0.24146 anti-myeloperoxidase 0.6911 0.8481 0.8163 0.3860
16 15 15 15 varl6 0.23497 0.32721 0.38832 0.85475 vanti-Fibronectin 0.3810 0.2339 0.1526 <.0001
16 15 15 15 varl7 0.40447 0.50226 0.28902 0.95925 anti-Factor VII 0.1202 0.0564 0.2961 <.0001
16 15 15 15 varl8 0.37087 0.48021 0.38347 0.92392 anti-tissue factor 0.1573 0.0700 0.1583 <.0001
16 15 15 15 varl9 0.30424 0.37976 0.16249 0.87793 anti-human complement 5b-9 0.2519 0.1627 0.5629 <.0001
16 15 15 15 var20 0.19825 0.31319 0.58513 0.80639 anti-human CRP 0.4617 0.2557 0.0219 0.0003
16 15 15 15 var21 0.85636 0.77212 0.14609 0.54597 anti-matrix GLA <.0001 0.0007 0.6034 0.0352
16 15 15 15
Pearson Correlation Coefficients Prob > I r I under HO : RhO=O Number of Observations var90 var91 var92 var93 varll -0.01375 0.35659 0.40558 0.04830 anti-prothrombin 0.9612 0.1920 0.1191 0.8590
15 15 16 16 varl2 0.92726 0.93549 0.85985 0.99001 anti-Factor IX <.0001 <.0001 <.0001 <.0001
15 15 16 16 varl3 0.72997 0.93149 0.88703 0.81880 anti-Fetuin B 0.0020 <.0001 <.0001 0.0001
15 15 16 16 varl4 0.40661 0.21533 0.04224 0.17569 anti-CD40 0.1326 0.4409 0.8766 0.5151
15 15 16 16 varl5 0.49882 0.39060 0.20077 0.30888 anti-myeloperoxidase 0.0584 0.1500 0.4559 0.2444
15 15 16 16 varl6 0.92471 0.86142 0.78859 0.92812 vanti-Fibronectin <.0001 <.0001 0.0003 ■c.OOOl
15 15 16 16 varl7 0.90355 0.95866 0.90290 0.95522 anti-Factor VII <.0001 <.0001 <.0001 <.0001
15 15 16 16 varl8 0.89337 0.93764 0.86536 0.96613 anti-tissue factor <.0001 <.0001 <.0001 <.0001 15 15 16 16 varl9 0.96844 0.92907 0.74990 0.98995 anti-human complement 5b-9 <.0001 <.0001 0.0008 <.0001
15 15 16 16 var20 0.83621 0.81715 0.75626 0.92874 anti-human CRP 0.0001 0.0002 0.0007 <.0001
IS 15 16 16 var21 0.46146 0.75722 0.57468 0.54815 anti-matrix GIA 0.0834 0.0011 0.0199 0.0279
15 15 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations
Capture varl var2 var3 var22 0.21537 0.25789 0.39993 0.37305 anti-CD61 0.4231 0.3349 0.1248 0.1547
16 16 16 16 var23 0.41533 0.46120 0.52797 0.48608 anti-Kappa Light Chain 0.1096 0.0722 0.0355 0.0563
16 16 16 16 var24 0.46976 0.58079 0.89027 0.88540 anti-Macrophage 0.0664 0.0183 <.0001 <.0001
16 16 16 16 var25 0.61302 0.74698 0.99224 0.99314 anti-factor XIIIA 0.0116 0.0009 <.0001 <.0001
16 16 16 16 var26 0.66343 0.80077 0.99203 0.96453 anti-hsp 60 0.0051 0.0002 <.0001 <.0001
16 16 16 16 var27 0.58715 0.72483 0.98986 0.99690 anti-fibrillin-1 0.0168 0.0015 <.0001 <.0001
16 16 16 16 var28 0.54689 0.53057 0.21140 0.08364 anti-B2 microgl 0.0284 0.0345 0.4319 0.7581
16 16 16 16 var29 0.57128 0.49230 0.10049 0.04146 anti-CD 18 0.0208 0.0527 0.7112 0.8788
16 16 16 16 var30 0.29338 0.39162 0.46122 0.42606 anti-1aminin 0.2701 0.1336 0.0722 0.0999
16 16 16 16 var31 0.35605 0.43030 0.42276 0.38843 anti-antitrypsin 0.1759 0.0962 0.1028 0.1371
16 16 16 16 var32 -0.06698 0.06560 -0.06241 -0.16035 anti-Notch-1 0.8053 0.8093 0.8184 0.5530
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var4 var5 var6 var7 var22 0.38151 0.36635 0.26629 0.24225 anti-CD61 0.1448 0.1628 0.3188 0.36S0
16 16 16 16 var23 0.49693 0.74506 0.40273 0.90335 anti-Kappa Light Chain 0.0502 0.0009 0.1220 <.0001
16 16 16 16 var24 0.89062 0.34946 0.47073 0.41264 anti-Macrophage <.0001 0.1846 0.0657 0.1122
16 16 16 16 var25 0.99360 0.40201 0.61145 0.51384 anti-factor XIIIA <.0001 0.1227 0.0118 0.0417
16 16 16 16 var26 0.97699 0.49105 0.66429 0.53450 anti-hsp 60 ■c.OOOl 0.0534 0.0050 0.0329
16 16 16 16 var27 0.99862 0.33755 0.58375 0.47275 anti-fibrillin-1 <.0001 0.2010 0.0176 0.0644
16 16 16 16 var28 0.12816 0.89012 0.52671 0.43907 anti-B2 microgl 0.6362 <.0001 0.0361 0.0889
16 16 16 16 var29 0.05860 0.55910 0.30744 0.01747 anti-CD 18 0.8293 0.0243 0.2467 0.9488
16 16 16 16 var30 0.43513 0.73362 0.34039 0.97764 anti-laminin 0.0921 0.0012 0.1970 <.0001
16 16 16 16 var31 0.39298 0.79589 0.39268 0.93324 anti-antitrypsin 0.1321 0.0002 0.1324 <.0001
16 16 16 16 var32 0.11793 0.44092 0.05534 0.30892 anti-Notch-1 0.6636 0.0874 0.8387 0.2443
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var8 var9 varlO varll var22 0.25991 0.35075 0.37088 0.15682 anti-CD61 0.3310 0.1829 0.1573 0.5619
16 16 16 16 var23 0.86217 0.44674 0.50100 0.26293 anti-Kappa Light Chain <.0001 0.0828 0.0481 0.3252
16 16 16 16 var24 0.49953 0.87154 0.88663 0.12901 anti-Macrophage 0.0488 <.0001 <.0001 0.6340
16 16 16 16 var25 0.68161 0.97139 0.99240 0.18856 anti-factor XIIIA 0.0036 <.0001 <.0001 0.4843
16 16 16 16 var26 0.71667 0.96222 0.97365 0.29769 anti-hsp 60 0.0018 <.0001 <.0001 0.2628
16 16 16 16 var27 0.62376 0.98317 0.99802 0.13348 anti-fibrillin-1 0.0098 <.0001 <.0001 0.6221
16 16 16 16 var28 0.67164 0.12094 0.11438 0.82693 anti-B2 microgl 0.0044 0.6555 0.6732 •=.0001
16 16 16 16 var29 0.26612 0.17435 0.05671 0.79726 anti-CD 18 0.3191 0.5184 0.8348 0.0002
16 16 16 IS var30 0 .87649 0 .37080 0 .43926 0 .15830 anti-laminin <.0001 0.1574 0.0887 0.5582
16 16 16 16 var31 0 .91061 0 .32715 0 .39483 0 .26228 anti-antitrypsin <.0001 0.2161 0.1302 0.3264
16 16 16 16 var32 0 .26533 -0 .14116 -0 .12839 0 .32157 anti-Notch-1 0.3206 0.6021 0.6356 0.2245
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations varl2 varl3 varl4 varlδ var22 0.36071 0.31378 0.16735 0.37312 anti-CD61 0.1699 0.2366 0.5356 0.1546
16 16 16 16 var23 0.43977 0.46081 0.87312 0.91216 anti-Kappa Light Chain 0.0883 0.0724 <.0001 <.0001
16 16 16 16 var24 0.88227 0.73338 0.17368 0.37979 anti-Macrophage <.0001 0.0012 0.5200 0.1468
16 16 16 16 var25 0.97522 0.87530 0.25680 0.41191 anti-factor XIIIA <.0001 <.0001 0.3370 0.1129
16 16 16 16 var26 0.96218 0.90334 0.29098 0.46862 anti-hsp 60 <.0001 <-0001 0.2742 0.0671
16 16 16 16 var27 0.98860 0.86957 0.19812 0.35540 anti-fibrillin-1 <.0001 <.0001 0.4620 0.1767
16 16 16 16 var28 0.08805 0.37279 0.52514 0.67260 anti-B2 microgl 0.7457 0.1550 0.0367 0.0043
16 16 16 16 var29 0.10882 0.38861 0.00164 0.13611 anti-CD 18 0.6883 0.1369 0.9952 0.6152
16 16 16 16 var30 0.37052 0.37669 0.95814 0.92988 anti-laminin 0.1577 0.1504 <.0001 <.0001
16 16 16 16 var31 0.31991 0.38391 0.93780 0.92070 anti-antitrypsin 0.2271 0.1421 <.0001 <.0001
16 16 16 16 var32 -0.13910 -0.07111 0.40537 0.34295 anti-Notch-1 0.6074 0.7936 0.1193 0.1935
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations varlS varl7 varlδ varl9 var22 0.33273 0.39401 0.37584 0.38078 anti-CD61 0.2079 0.1310 0.1514 0.1457
16 16 16 16 var23 0.45662 0.54324 0.46279 0.52607 anti-Kappa Light Chain 0.0754 0.0297 0.0711 0.0363
16 16 16 16 var24 0.79898 0.87614 0.88430 0.87265 anti-Macrophage 0.0002 ■=.0001 <.0001 <.0001
16 16 16 16 var25 0.93930 0.97890 0.99054 0.95941 anti-factor XIIIA <.0001 <.0001 <.0001 <.0001
16 16 16 16 var26 0.90979 0.98003 0.97832 0.95390 anti-hsp 60 <.0001 <.0001 <.0001 <.0001
16 16 16 16 var27 0.94775 0.97691 0.99207 0.96645 anti-fibrillin-1 <.0001 <-0001 ■ς.0001 <.0001
16 16 16 16 var28 0.07964 0.23914 0.17162 0.12142 anti-B2 microgl 0.7694 0.3724 0.5251 0.6542
16 16 16 16 var29 0.06183 0.24512 0.15208 -0.03540 anti-CD 18 0.8200 0.3602 0.5739 0.8964
16 16 16 16 var30 0.42521 0.46595 0.39338 0.46982 anti-laminin 0.1006 0.0689 0.1317 0.0663
16 16 16 16 var31 0.37951 0.43651 0.36798 0.40176 anti-antitrypsin 0.1471 0.0909 0.1608 0.1229
16 16 16 16 var32 0.23721 -0.08381 -0.11789 -0.05027 anti-Notch-1 0.3764 0.7576 0.6637 0.8533
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var20 var21 var22 var23 var22 0.30351 0.29536 1.00000 0.41255 anti-CD61 0.2531 0.2667 0.1123
16 16 16 16 var23 0.32727 0.40286 0.41255 1.00000 anti-Kappa Light Chain 0.2160 0.1218 0.1123
16 16 16 16 var24 0.83034 0.51509 0.66760 0.51163 anti-Macrophage <.0001 0.0412 0.0047 0.0428
16 16 16 16 var25 0.94827 0.64331 0.37370 0.53359 anti-factor XIIIA <.0001 0.0072 0.1539 0.0333
16 16 16 16 var26 0.89075 0.70702 0.39789 0.56801 anti-hsp 60 <.0001 . 0.0022 0.1269 0.0217
16 16 16 16 var27 0.95630 0.61519 0.35949 0.48217 anti-fibrillin-1 <.0001 0.0112 0.1715 0.0586
16 16 16 16 var28 -0.07436 0.58061 0.24475 0.62876 anti-B2 microgl 0.7843 0.0184 0.3609 0.0091
16 16 16 16 var29 0.07019 0.28654 -0.01121 0.17911 anti-CD 18 0.7962 0.2819 0.9671 0.5069
IS 16 16 16 var30 0.28790 0.33086 0.24651 0.94210 anti-laminin 0.2796 0.2107 0.3574 ■c.OOOl
16 16 16 16 var31 0.26105 0.37979 0.22491 0.93636 anti-antitrypsin 0.3288 0.1468 0.4023 <.0001
16 16 16 16 var32 0.24971 0.14430 -0.08537 0.23586 anti-Notch-1 0.3510 0.5939 0.7533 0.3792
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var24 var25 var26 var27 var22 0.66760 0.37370 0.39789 0.35949 anti-CD61 0.0047 0.1539 0.1269 0.1715
16 16 16 16 var23 0.51163 0.53359 0.56801 0.48217 anti-Kappa Light Chain 0.0428 0.0333 0.0217 0.0586
16 16 16 16 var24 1.00000 0.87973 0.86309 0.88120 anti-Macrophage <.0001 <.0001 <.0001
16 16 16 16 var25 0.87973 1.00000 0.98636 0.99368 anti-factor XIIIA <.0001 <.0001 <.0001
16 16 16 16 var26 0.86309 0.98636 1.00000 0.97210 anti-hsp 60 <.0001 <.0001 <-0001
16 16 16 16 var27 0.88120 0.99368 0.97210 1.00000 anti-fibrillin-1 <.0001 <.0001 <.0001
16 16 16 16 var28 0.14267 0.18091 0.29753 0.10606 anti-B2 microgl 0.5981 0.5025 0.2631 0.6959
16 16 16 16 var29 0.01606 0.08426 0.15491 0.06273 anti-CD 18 0.9529 0.7564 0.5668 0.8175
16 16 16 16 var30 0.36284 0.48089 0.51630 0.42673 anti-laminin 0.1672 0.0593 0.0406 0.0993
16 16 16 16 var31 0.31905 0.44961 0.48647 0.38661 anti-antitrypsin 0.2284 0.0806 0.0560 0.1391
16 16 16 16 var32 -0.19289 -0.08228 0.01862 -0.14179 anti-Notch-1 0.4741 0.7620 0.9454 0.6004
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var28 var29 var30 var31 var22 0.24475 -0.01121 0.24651 0.22491 anti-CD61 0.3609 0.9671 0.3574 0.4023
16 16 16 16 var23 0.62876 0.17911 0.94210 0.93636 anti-Kappa Light Chain 0.0091 0.5069 <.0001 <.0001
16 16 16 16 var24 0.14267 0.01606 0.36284 0.31905 anti-Macrophage 0.5981 0.9529 0.1672 0.2284
16 16 16 16 var25 0.18091 0.08426 0.48089 0.44961 anti-factor XIIIA 0.5025 0.7564 0.0593 0.0806
16 16 16 IS var26 0.29753 0.15491 0.51630 0.48647 anti-hsp 60 0.2631 0.5668 0.0406 0.0560
16 16 16 16 var27 0.10606 0.06273 0.42673 0.38661 anti-fibrillin-1 0.6959 0.8175 0.0993 0.1391
16 16 16 16 var28 1.00000 0.53483 0.57063 0.65267 anti-B2 microgl 0.0328 0.0210 0.0061
16 16 16 16 var29 0.53483 1.00000 0.12037 0.19633 anti-CD 18 0.0328 0.6570 0.4662
16 16 16 16 var30 0.57063 0.12037 1.00000 0.98338 anti-laminin 0.0210 0.6570 <.0001
16 16 16 16 var31 0.65267 0.19633 0.98338 1.00000 anti-antitrypsin 0.00S1 0.4662 <.0001
16 16 16 16 var32 0.55190 0.09054 0.36006 0.39789 anti-Notch-1 0.0267 0.7388 0.1707 0.1269
16 16 16 16
Pearson Correlation Coefficients Prob :> I r I under HO : RhO=O Number of Observations var32 var33 var34 var35 var22 -0.08537 0.34704 0.39055 0.082S4 anti-CD61 0.7533 0.1879 0.1348 0.7612
16 16 16 16 var23 0.23586 0.44914 0.44007 0.14353 anti-Kappa Light Chain 0.3792 0.0809 0.0880 0.5959
16 16 16 16 var24 -0.19289 0.86026 0.84110 0.43600 anti-Macrophage 0.4741 <.0001 <.0001 0.0914
16 16 16 16 var25 -0.08228 0.96413 0.93306 0.57323 anti-factor XIIIA 0.7620 <.0001 <.0001 0.0203
16 16 16 16 var26 0.01862 0.95517 0.93686 0.54811 anti-hsp 60 0.9454 <.0001 <.0001 0.0279
16 16 16 16 var27 -0.14179 0.97225 0.92755 0.60544 anti-fibrillin-1 0.6004 <.0001 <.0001 0.0129
16 16 16 16 var28 0.55190 0.15417 0.18694 -0.18905 anti-B2 microgl 0.0267 0.5686 0.4882 0.4832
16 16 16 16 var29 0.09054 0.26345 -0.01452 -0.14470 anti-CD 18 0.7388 0.3242 0.9574 0.5929
16 16 16 16 var30 0.36006 0.36737 0.34083 0.11391 anti-laminin 0.1707 0.1616 0.1964 0.6745
16 16 16 16 var31 0.39789 0.33736 0.30279 0.05073 anti-antitrypsin 0.1269 0.2013 0.2543 0.8520
IS 16 16 16 var32 1.00000 -0.15118 -0.05345 0.06710 anti-Notch-1 0.5762 0.8441 0.8050
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var36 var37 var38 var39 var22 0.38364 0.38385 0.27271 0.34896 anti-CD61 0.1424 0.1422 0.3068 0.1853
16 16 16 16 var23 0.49407 0.47127 0.15488 0.44512 anti-Kappa Light Chain 0.0518 0.0654 0.5668 0.0840
16 16 16 16 var24 0.87830 0.86531 0.45692 0.87408 anti-Macrophage <.0001 <.0001 0.0752 <.0001
16 16 16 16 var25 0.96503 0.98412 0.45509 0.97309 anti-factor XIIIA <.0001 <.0001 0.0765 <.0001
16 16 16 16 var26 0.95738 0.97468 0.50708 0.95756 anti-hsp 60 <.0001 <.0001 0.0450 <.0001
16 16 16 16 var27 0.97301 0.97556 0.46042 0.98571 anti-fibril1in-1 <-0001 <.0001 0.0727 <.0001
16 16 16 16 var28 0.09271 0.20770 0.43198 0.08346 anti-B2 microgl 0.7327 0.4402 0.0947 0.7586
16 16 16 16 var29 -0.03140 0.20438 0.20193 0.14173 anti-CD 18 0.9081 0.4477 0.4533 0.6006
16 16 16 16 var30 0.43686 0.39787 0.13902 0.37286 anti-laminin 0.0907 0.1270 0.6076 0.1549
16 16 16 16 var31 0 .36980 0.38696 0.16325 0.32490 anti-antitrypsin 0.1586 0.1387 0.5458 0.2195
16 16 16 16 var32 -0 .07404 -0.11429 0.25820 -0.15869 anti-Notch-1 0.7852 0.6734 0.3343 0.5572
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var40 var41 var42 var43 var22 0.27382 0.32330 0.51333 0.58487 anti-CD61 0.3048 0.2219 0.0420 0.0173
16 16 16 16 var23 0.31802 0.44440 0.39253 0.41908 anti-Kappa Light Chain 0.2300 0.0846 0.1326 0.1062
16 16 16 16 var24 0.65172 0.69826 0.83966 0.93812 anti-Macrophage 0.0062 0.0026 <.0001 <.0001
16 16 16 16 var25 0.73285 0.84151 0.84762 0.90312 anti-factor XIIIA 0.0012 ■=.0001 ■c.OOOl <.0001
16 16 16 16 var26 0.77735 0.87401 0.83824 0.87982 anti-hsp 60 0.0004 <.0001 ς.OOOl <.0001
16 16 16 16 var27 0.73723 0.83100 0.87163 0.92579 anti-fibrillin-1 0.0011 ■=.0001 ς.OOOl <.0001
16 16 16 16 var28 0.42984 0.40174 -0.00173 -0.02820 anti-B2 microgl 0.0966 0.1230 0.9949 0.9174
16 16 16 16 var29 0.58575 0.31503 0.10311 -0.06297 anti-CD 18 0.0171 0.2347 0.7039 0.8168
16 16 16 16 var30 0.25350 0.36940 0.28943 0.31844 anti-laminin 0.3435 0.1591 0.2769 0.2294
16 16 16 16 var31 0.27059 0.38484 0.21567 0.24384 anti-antitrypsin 0.3108 0.1410 0.4224 0.3628
16 16 16 16 var32 0.05325 -0.04759 -0.20127 -0.21857 anti-Notch-1 0.8447 0.8S11 0.4548 0.4161
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var45 var46 var47 var48 var22 -0.02318 0.12040 0.37343 0.22206 anti-CD61 0.9321 0.6569 0.1542 0.4085
16 16 16 16 var23 0.03432 0.81032 0.31643 0.26387 anti-Kappa Light Chain 0.8996 0.0001 0.2325 0.3234
16 16 16 16 var24 0.18753 0.10917 0.73097 0.29990 anti-Macrophage 0.4868 0.6873 0.0013 0.2591
16 16 16 16 var25 0.29354 0.25829 0.72439 0.38558 anti-factor XIIIA 0.2698 0.3341 0.0015 0.1402
16 16 16 16 var26 0.26701 0.30156 0.75436 0.46756 anti-hsp 60 0.3175 0.2564 0.0007 0.0678
16 16 16 16 var27 0.30991 0.20321 0.73183 0.35658 anti-fibrillin-1 0.2428 0.4503 0.0013 0.1752 16 16 16 16 var28 0.16207 0.62380 0.37651 0.67969 anti-B2 microgl 0.5487 0.0098 0.1505 0.0038
16 16 16 16 var29 0.15529 0.19585 0.18601 0.53903 anti-CD 18 0.5658 0.4673 0.4904 0.0312
16 16 16 16 var30 0.03930 0.91040 0.17721 0.20989 anti-1aminin 0.8851 <-0001 0.5115 0.4353
16 16 16 16 var31 0.00522 0.91505 0.19549 0.29548 anti-antitrypsin 0.9847 <.000l 0.4681 0.2665
16 16 16 16 var32 0.21549 0.327S2 0.09473 0.26500 anti-Notch-1 0.4228 0.2156 0.7271 0.3213
IS 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var49 varSO var51 var52 var22 0.17383 0.21688 0.52676 0.33094 anti-CD61 0.5197 0.4198 0.0360 0.2106
16 16 16 16 var23 0.31423 0.39226 0.61892 0.40017 anti-Kappa Light Chain 0.2359 0.1329 0.0106 0.1246
16 16 16 16 var24 0.35097 0.62911 0.86729 0.85371 anti-Macrophage 0.1826 0.0090 <.0001 <.0001
16 16 16 16 var25 0.48041 0.74082 0.90336 0.97463 anti-factor XIIIA 0.0596 0.0010 <.0001 <.0001
16 16 16 16 var26 0.55695 0.76214 0.87233 0.94907 anti-hsp 60 0.0250 0.0006 <.0001 <.0001
16 16 16 16 var27 0.45813 0.74109 0.89602 0.97795 anti-fibrillin-1 0.0743 0.0010 •=.0001 <.0001
16 16 16 16 var28 0.62362 0.27241 0.16820 0.12842 anti-B2 microgl 0.0098 0.3074 0.5335 0.6355
16 16 16 16 var29 0.53210 0.66159 0.20016 0.15670 anti-CD 18 0.0339 0.0053 0.4573 0.5622
16 16 16 16 var30 0.21456 0.29931 0.53798 0.34163 anti-laminin 0.4249 0.2601 0.0316 0.1953
16 16 16 16 var31 0.28601 0.29635 0.51459 0.33011 anti-antitrypsin 0.2829 0.2651 0.0414 0.2118
16 16 16 16 var32 0.10982 -0.11374 -0.29282 -0.15691 anti-Notch-1 0.6856 0.6749 0.2711 0.5617
16 16 16 16
Pearson Correlation Coefficients Prob > | r| under HO : RhO=O Number of Observations var53 var54 var55 var5β var22 0.34213 -0.09464 0.24944 0.22494 anti-CDSl 0.1946 0.7274 0.3515 0.4023
16 16 16 16 var23 0.63373 0.04480 0.25135 0.38417 anti-Kappa Light Chain 0.0084 0.8691 0.3477 0.1418
16 16 16 16 var24 0.82281 0.02942 0.54073 0.67551 anti-Macrophage <.0001 0.9139 0.0306 0.0041
16 16 16 16 var25 0.95139 0.15948 0.58716 0.78264 anti-factor XIIIA <.0001 0.5552 0.0168 0.0003
16 16 16 16 var2S 0.91751 0.14194 0.64760 0.79702 anti-hsp 60 <.0001 0.6000 0.0067 0.0002
16 16 16 16 var27 0.94240 0.13294 0.59109 0.79080 anti-fibrillin-1 <.0001 0.6236 0.0159 0.0003
16 16 16 16 var28 0.12246 0.17927 0.49238 0.21602 anti-B2 microgl 0.6514 0.5065 0.0527 0.4217
16 16 16 16 var29 -0.06106 0.76639 0.64050 0.59164 anti-CD 18 0.8223 0.0005 0.0075 0.0158
16 16 16 16 var30 0.63377 0.01292 0.18810 0.29522 anti-1aminin 0.0084 0.9621 0.4854 0.2670
16 16 16 16 var31 0.58898 0.11505 0.21661 0.27810 anti-antitrypsin 0.0164 0.6714 0.4204 0.2970
16 16 16 16 var32 -0.05715 -0.20487 0.13109 -0.14091 anti-Notch-1 0.8335 0.4466 0.6284 0.6027
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var57 var58 var59 var60 var22 0.29462 0.21692 0.40463 0.14342 anti-CD61 0.2680 0.4197 0.1200 0.5962
16 16 16 16 var23 0.37058 0.60158 0.50236 0.33199 anti-Kappa Light Chain 0.1577 0.0137 0.0474 0.2090
16 16 16 16 var24 0.48215 0.44511 0.67769 0.51345 anti-Macrophage 0.0586 0.0840 0.0039 0.0419
16 16 16 16 var25 0.55904 0.56862 0.77415 0.62279 anti-factor XIIIA 0.0244 0.0215 0.0004 0.0100
16 16 16 16 var26 0.63228 0.62135 0.83905 0.64657 anti-hsp 60 0.0086 0.0102 <.0001 0.0068
16 16 16 16 var27 0.53890 0.53531 0.73388 0.62478 anti-fibrillin-1 0.0312 0.0326 0.0012 0.0097
16 16 16 16 var28 0.62S45 0.66042 0.61188 0.27318 anti-B2 microgl 0.0094 0.0054 0.0118 0.3060
16 16 16 16 var29 0.24026 0.47712 0.32020 0.76254 anti-CD 18 0.3701 0.0617 0.2266 0.0006
16 16 16 16 var30 0.25531 0.52320 0.37758 0.24385 anti-laminin 0.3399 0.0376 0.1494 0.3628
16 16 16 16 var31 0.30454 0.58180 0.40682 0.25247 anti-antitrypsin 0.2515 0.0181 0.1179 0.3455
16 16 16 16 var32 0.19535 0.06370 0.17611 -0.12495 anti-Notch-1 0.4684 0.8147 0.5141 0.6447
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var61 var62 var63 var64 var22 0.40634 0.40248 0.38460 0.33089 anti-CD61 0.1183 0.1222 0.1413 0.2106
16 16 16 16 var23 0.53714 0.47376 0.47851 0.39220 anti-Kappa Light Chain 0.0319 0.0638 0.0608 0.1330
16 16 16 16 var24 0.77604 0.65030 0.81767 0.87107 anti-Macrophage 0.0004 0.0064 0.0001 <.0001
16 16 16 16 var25 0.87119 0.74619 0.92749 0.96934 anti-factor XIIIA <.0001 0.0009 <.0001 <.0001
16 16 16 16 var26 0.90743 0.81597 0.95255 0.94312 anti-hsp 60 <.0001 0.0001 <.0001 <-0001
16 16 16 16 var27 0.84650 0.71363 0.92365 0.98718 anti-fibrillin-1 <.0001 0.0019 <.0001 <.0001
16 16 16 16 var28 0.38825 0.56782 0.36179 0.00400 anti-B2 microgl 0.1373 0.0218 0.1685 0.9883
16 16 16 16 var29 0.09001 0.14421 0.22794 0.03748 anti-CD 18 0.7403 0.5942 0.3959 0.8904
16 16 16 16 var30 0.42825 0.38008 0.39461 0.32971 anti-laminin 0.0979 0.1465 0.1304 0.2124
16 16 16 16 var31 0.40472 0.38601 0.38756 0.27582 anti-antitrypsin 0.1200 0.1397 0.1380 0.3011
16 16 16 16 var32 0.08377 0.17657 -0.01028 -0.17696 anti-Notch-1 0.7577 0.5130 0.9698 0.5121
16 16 16 16 Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var65 varS6 var67 varδβ var22 0.28951 0.40822 0.28597 0.47689 anti-CD61 0.2768 0.1165 0.2829 0.0618
16 IS 16 16 var23 0.4757S 0.47283 0.25046 0.32901 anti-Kappa Light Chain 0.0625 0.0644 0.3495 0.2134
IS 16 -16 16 var24 0.69820 0.78845 0.58568 0.72257 anti-Macrophage 0.0026 0.0003 0.0171 0.0016
16 16 16 16 var25 0.80563 0.88287 0.57325 0.64678 anti-factor XIIIA 0.0002 <.0001 0.0203 0.0068
16 16 16 16 var26 0.82757 0.92672 0.52746 0.67135 anti-hsp εo <.0001 ■c.OOOl 0.0358 0.0044
16 16 16 16 var27 0.80614 0.87102 0.62351 0.65394 anti-fibrillin-1 0.0002 <.0001 0.0099 0.0060
16 16 16 16 var28 0.32674 0.40956 -0.17081 0.16420 anti-B2 microgl 0.2168 0.1152 0.5271 0.5434
16 16 16 16 var29 0.13972 0.12485 -0.08778 0.16111 anti-CD 18 0.6058 0.6450 0.7465 0.5511
16 16 16 16 var30 0.37485 0.38881 0.11340 0.13694 anti-laminin 0.1526 0.1367 0.6758 0.6131
16 16 16 16 var31 0.37037 0.36939 0.07338 0.11746 anti-antitrypsin 0.1579 0.1591 0.7871 0.6648
16 16 16 16 var32 0.05781 0.07932 -0.40034 -0.09636 anti-Notch-1 0.8316 0.7703 0.1244 0.7226
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var69 var70 var71 var72 var22 -0.04982 0.20565 0.21673 0.50831 anti-CD61 0.8546 0.4448 0.4201 0.0444
16 16 16 16 var23 -0.07514 0.36143 0.37019 0.54559 anti-Kappa Light Chain 0.7821 0.1690 0.1581 0.0288
16 16 16 16 var24 -0.01632 0.47125 0.49907 0.80477 anti-Macrophage 0.9522 0.0654 0.0491 0.0002
16 16 16 16 var25 -0.00277 0.62094 0.62795 0.88124 anti-factor XIIIA 0.9919 0.0103 0.0092 <.0001
16 16 16 16 var26 -0.02433 0.S5707 0.67456 0.91710 anti-hsp 60 0.9287 0.0057 0.0042 <.0001
16 16 16 16 var27 0.00476 0.61487 0.62615 0.85460 anti-fibrillin-1 0.9860 0.0113 0.0095 <.0001
16 16 16 16 var28 0.11775 0.43094 0.47471 0.47191 anti-B2 microgl 0.6641 0.0956 0.0632 0.0650
16 16 16 16 var29 0.07612 0.38816 0.35087 0.40126 anti-CD 18 0.7793 0.1374 0.1827 0.1235
16 16 16 16 var30 0.05449 0.27936 0.28579 0.43645 anti-1aminin 0.8411 0.2947 0.2833 0.0910
16 16 16 16 var31 0.03480 0.32948 0.32729 0.45442 anti-antitrypsin 0.8982 0.2127 0.2159 0.0770
16 16 16 16 var32 0.19049 -0.07057 0.00714 0.00418 anti-Notch-1 0.4798 0.7951 0.9791 0.9878
16 • 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var74 var75 var76 var77 var22 0.27408 0.25279 0.28089 0.12496 anti-CD61 0.3043 0.3449 0.2920 0.6447
16 16 16 16 var23 0.38757 0.42549 0.42965 0.49909 anti-Kappa Light Chain 0.1380 0.1004 0.0967 0.0491
16 16 16 16 var24 0.39007 0.47632 0.47975 0.38345 anti-Macrophage 0.1353 0.0622 0.0600 0.1426
16 16 16 16 var25 0.49981 0.59027 0.58972 0.51624 anti-factor XIIIA 0.0487 0.0161 0.0162 0.0406
16 16 16 16 var26 0.57436 0.66022 0.65849 0.52604 anti-hsp 60 0.0200 0.0054 0.0055 0.0363
16 16 16 16 var27 0.46607 0.56387 0.56222 0.49485 anti-fibrillin-1 0.0688 0.0229 0.0234 0.0513
16 16 16 16 var28 0.67016 0.65566 0.64894 0.46085 anti-B2 microgl 0.0045 0.0058 0.0065 0.0724
16 16 16 16 var29 0.48158 0.70844 0.69568 0.36963 anti-CD 18 0.0589 0.0021 0.0028 0.1588
16 16 16 16 var30 0.30589 0.32558 0.33665 0.43507 anti-laminin 0.2492 0.2185 0.2023 0.0921
16 16 16 16 var31 0.38207 0.39411 0.40391 0.50848 anti-antitrypsin 0.1442 0.1309 0.1208 0.0443
16 16 16 16 var32 0.13563 0.08541 0.08062 0.02011 anti-Notch-1 0.6165 0.7531 0.7666 0.9411
16 16 16 16 Pearson Correlation Coefficients Prob > I r I under HO : RhO=O Number of Observations var78 var79 var80 varδl var22 0.31054 0.203S3 0.28317 0.30684 anti-CD61 0.2418 0.4496 0.2879 0.3079
16 16 16 13 var23 0.68348 0.28704 0.40430 0.32168 anti-Kappa Light Chain 0.0035 0.2811 0.1204 0.2838
16 16 16 13 var24 0.73429 0.30063 0.45887 0.64069 anti-Macrophage 0.0012 0.2579 0.0738 0.0183
16 16 16 13 var25 0.89379 0.39160 0.57354 0.75980 anti-factor XIIIA <.0001 0.1336 0.0202 0.0026
16 16 16 13 var26 0.85524 0.46587 0.64315 0.69004 anti-hsp 60 <.0001 0.0690 0.0072 0.0090
16 16 16 13 var27 0.86565 0.36281 0.54586 0.74362 anti-fibrillin-1 <.0001 0.1672 0.0287 0.0036
16 16 16 13 var28 0.22928 0.67326 0.65255 -0.08034 anti-B2 microgl 0.3930 0.0043 0.0061 0.7942
16 16 16 13 var29 0.06561 0.48866 0.52424 -0.16507 anti-CD 18 0.8092 0.0548 0.0371 0.5900
16 16 16 13 var30 0.67583 0.24523 0.31718 0.30240 anti-laminin 0.0041 0.3600 0.2313 0.3153
16 16 16 13 var31 0.67640 0.33280 0.39030 0.30984 anti-antitrypsin 0.0040 0.2078 0.1350 0.3029
16 16 16 13 var32 0.07247 0.22819 0.12247 -0.35933 anti-Notch-1 0.7897 0.3953 0.6514 0.2279
16 16 16 13
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var82 var83 var84 var85 var22 0.22772 0.26621 0.19408 0.22301 anti-CD61 0.4543 0.3793 0.5252 0.4640
13 13 13 13 var23 0.25043 0.42017 0.37841 0.36884 anti-Kappa Light Chain 0.4092 0.1529 0.2023 0.2149
13 13 13 13 var24 0.50640 0.65650 0.59977 0.44385 anti-Macrophage 0.0774 0.0148 0.0303 0.1287
13 13 13 13 var25 0.57854 0.77360 0.71544 0.56577 anti-factor XIIIA 0.0383 0.0019 0.0060 0.0439
13 13 13 13 var26 0.63416 0.82640 0.74754 0.63719 an.ti-b.sp 60 0.0199 0.0005 0.0033 0.0192
13 13 13 13 var27 0.57667 0.76547 0.71446 •0.54498 anti-fibrillin-1 0.0391 0.0023 0.0061 0.0541
13 13 13 13 var28 0.47768 0.52272 0.32356 0.65713 anti-B2 microgl 0.0988 0.0668 0.2809 0.0147
13 13 13 13 var29 0.24791 0.64874 0.67284 0.73526 anti-CD 18 0.4141 0.0165 0.0117 0.0042
13 13 13 13 var30 0.22648 0.32738 0.26638 0.31167 anti-laminin 0.4568 0.2749 0.3790 0.2999
13 13 13 13 var31 0.25167 0.34773 0.26635 0.36828 anti-antitrypsia 0.4068 0.2443 0.3791 0.2157
13 13 13 13 var32 0.30626 0.01168 -0.13013 0.08622 anti-Notch-1 0.3088 0.9698 0.6718 0.7794
13 13 13 13
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var86 var87 var88 var89 var22 0.05963 0.07123 -0.01943 0.28179 anti-CD61 0.8264 0.8009 0.9452 0.3089
16 15 15 15 var23 0.23780 0.10912 -0.04305 0.40914 anti-Kappa Light Chain 0.3751 0.6987 0.8789 0.1299
16 15 15 15 var24 0.21783 0.31953 0.23308 0.79133 anti-Macrophage 0.4177 0.2457 0.4031 0.0004
16 15 15 15 var25 0.34017 0.42678 0.38751 0.89479 anti-factor XIIIA 0.1973 0.1126 0.1536 <.0001
16 15 15 15 var26 0.40451 0.48423 0.29364 0.89956 anti-hsp 60 0.1202 0.0674 0.2881 <.0001
16 15 15 15 var27 0.33571 0.44580 0.36860 0.90855 anti-fibrillin-1 0.2037 0.0958 0.1764 <.0001
16 15 15 15 var28 0.48755 0.29018 -0.20129 0.13548 anti-B2 microgl 0.0554 0.2941 0.4719 0.6302
16 15 15 15 var29 0.40572 0.48447 -0.03521 0.38106 anti-CD 18 0.1190 0.0672 0.9009 0.1611
16 15 15 15 var30 0.15923 0.09587 -0.01090 0.32655 anti-laminin 0.5558 0.7340 0.9692 0.2349
16 15 15 15 var31 0.21697 0.10963 0.06935 0.28539 anti-antitrypsin 0.4196 0.6973 0.8060 0.3025 16 15 15 15 var32 0.09605 0.00141 -0.26377 -0.13603 anti-Notch-1 0.7235 0.9960 0.3422 0.6288
16 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var90 var91 var92 var93 var22 0.34787 0.35555 0.21047 0.35786 anti-CD61 0.2039 0.1934 0.4340 0.1735
15 15 16 16 var23 0.59281 0.55086 0.38958 0.44471 anti-Kappa Light Chain 0.0199 0.0333 0.1358 0.0844
15 15 16 16 var24 0.81509 0.81524 0.69475 0.88083 anti-Macrophage 0.0002 0.0002 0.0028 <.0001
15 15 16 16 var25 0.92104 0.93846 0.82751 0.96984 anti-factor XIIIA <.0001 <.0001 <.0001 <.0001
15 15 16 16 var26 0.91406 0.96348 0.82293 0.94976 anti-hsp 60 <.0001 <.0001 <.0001 <.0001
15 15 16 16 var27 0.92859 0.92813 0.83603 0.98437 anti-fibrillin-1 <.0001 <.0001 <.0001 <.0001
15 15 16 16 var28 0.10430 0.32557 0.18775 0.03568 anti-B2 microgl 0.7114 0.2364 0.4862 0.8956
15 15 16 16 var29 -0.05699 0.20112 0.53809 -0.02353 anti-CD 18 0.8401 0.4723 0.0315 0.9311
15 15 16 16 var30 0.58160 0.45893 0.30412 0.38924 anti-laminin 0.0230 0.0853 0.2521 0.1362
15 15 16 16 var31 0.49631 0.43517 0.30531 0.32536 anti-antitrypsin 0.0599 0.1050 0.2502 0.2188
15 15 16 16 var32 -0.03387 0.03050 -0.18950 -0.12895 anti-Notch-1 0.9046 0.9141 0.4821 0.6341
15 15 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations
Capture varl var2 var3 var33 0.65841 0.77003 0.96906 0.96654 anti-BSA 0.0056 0.0005 <.0001 <.0001
16 16 16 16 var34 0.60363 0.70955 0.95087 0.92782 anti-LBP 0.0133 0.0021 <.0001 <.0001
16 16 16 16 var35 0.07772 0.25857 0.57869 0.60340 anti-PTX3 0.7748 0.3336 0.0188 0.0133
16 16 16 16 var3S 0.50372 0.66261 0.97807 0.96763 anti-complement C5 0.0467 0.0052 <.0001 <.0001
16 16 16 16 var37 0.69009 0.79671 0.97580 0.97655 anti-fibrinogen 0.0031 0.0002 <.0001 <.0001
16 16 16 16 var38 0.37031 0.52970 0.49388 0.41161 anti-D-Dimer 0.1580 0.0348 0.0519 0.1132
16 16 16 16 var39 0.59148 0.71951 0.97935 0.98118 anti-factor V 0.0158 0.0017 <.0001 <.0001
16 16 16 16 var40 0.71298 0.82790 0.75182 0.70055 anti-human gamma-Gla 0.0019 <.0001 0.0006 0.0025
16 16 16 16 var41 0.88746 0.97162 0.85852 0.80681 anti-TF-VIIa <.0001 <.0001 <.0001 0.0002
16 16 16 16 var42 0.47842 0.62818 0.86629 0.86555 anti-complement C3c 0.0608 0.0092 <.0001 <.0001
16 16 IS 16 var43 0.41587 0.56614 0.91864 0.92626 anti-Complement C4 0.1091 0.0222 <.0001 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var4 var5 var6 var7 var33 0.97197 0.36622 0.57620 0.39922 anti-BSA <.0001 0.1S30 0.0195 0.1256
16 16 16 16 var34 0.94046 0.26377 0.59200 0.36591 anti-LBP <.0001 0.3236 0.0157 0.1634
16 16 16 16 var35 0.61061 -0.0939S 0.08403 0.20732 anti-PTX3 0.0120 0.7293 0.7570 0.4410
16 16 16 16 var36 0.98091 0.27642 0.51641 0.50034 anti-complement C5 <.0001 0.3000 0.0406 0.0484
16 16 16 16 var37 0.97352 0.41830 0.64895 0.41141 anti-fibrinogen <.0001 0.1069 0.0065 0.1134
16 16 16 16 var38 0.46439 0.54893 0.52695 0.14459 anti-D-Dimer 0.0700 0.0277 0.0360 0.5932
16 16 16 16 var39 0.98705 0.29504 0.53743 0.42224 anti-factor V <.0001 0.2673 0.0318 0.1033
16 16 16 16 var40 0.73614 0.60405 0.65865 0.24298 anti-human gamma-Gla 0.0011 0.0132 0.0055 0.3645
16 16 16 16 var41 0.82823 0.54333 0.92353 0.32507 anti-TF-VIIa <.0001 0.0296 <.0001 0.2193
16 16 16 16 var42 0.87736 0.20110 0.45404 0.35220 anti-complement C3c <.0001 0.4552 0.0773 0.1809
16 16 16 16 var43 0.9337S 0.19627 0.42876 0.39611 anti-Complement C4 <.0001 0.4663 0.0975 0.1288
16 16 16 ie
Pearson Correlation Coefficients Prob > I r I under HO : RhO=O Number of Observations var8 var9 varlO varll var33 0.58095 0.99365 0.97282 0.27248 anti-BSA 0.0183 <.0001 <-0001 0.3073
16 16 16 16 var34 0.55675 0.92864 0.94101 0.22301 anti-LBP 0.0251 <.0001 <.0001 0.4064
16 16 16 16 var35 0.12530 0.62035 0.61538 -0.13829 anti-PTX3 0.6438 0.0104 0.0112 0.6095
16 16 16 16 var36 0.57206 0.96882 0.98274 0.07474 anti-complement CS 0.0206 <.O001 <.0001 0.7833
16 16 16 16 var37 0.65306 0.96756 0.97110 0.30097 anti-fibrinogen 0.0061 <.0001 <.0001 0.2573
16 16 16 16 var38 0.35461 0.44673 0.43407 0.42187 anti-D-Dimer 0.1778 0.0828 0.0930 0.1036
16 16 16 16 var39 0.55581 0.99848 0.98936 0.16455 anti-factor V 0.0254 <.0001 <.0001 0.5425
16 16 16 16 var40 0.52423 0.78834 0.72223 0.60398 anti-human gamma-Gla 0.0371 0.0003 0.0016 0.0132
16 16 16 16 var41 0.70764 0.83422 0.82004 0.48652 anti-TF-VIIa 0.0022 <.0001 0.0001 0.0560
16 16 16 16 var42 0.40104 0.90526 0.88148 0.08540 anti-complement C3c 0.1237 <.0001 <.0001 0.7532
16 16 16 16 var43 0.43000 0.92716 0.93429 -0.01204 anti-Complement C4 0.0964 <.0001 <.O001 0.9647
16 16 16 16
Pearson Correlation Coefficients Prob > I rI under HO : Rho=0 Number of Observations varl2 varl3 varl4 varl5 var33 0.98495 0.90296 0.12098 0.29782 anti-BSA <.0001 <.0001 0.6554 0.2626
16 16 16 16 var34 0.93321 0.83381 0.13351 0.29197 anti-LBP <.0001 <.0001 0.6220 0.2725
16 16 16 16 var35 0.63897 0.39639 -0.00392 0.00390 anti-PTX3 0.0077 0.1285 0.9885 0.9886 16 16 16 16 var36 0.98050 0.81799 0.23153 0.36299 anti-complement C5 ■c.OOOl 0.0001 0.3882 0.1670
16 16 16 16 var37 0.96202 0.90874 0.15683 0.34273 anti-fibrinogen <.0001 ■c.OOOl 0.5619 0.1938
16 16 16 16 var38 0.45428 0.52545 0.00683 0.27770 anti-D-Dimer 0.0771 0.0366 0.9800 0.2977
16 16 16 16 var39 0.99792 0.87162 0.13734 0.29281 anti-factor V <.0001 <.0001 0.6120 0.2711
16 16 IS 16 var40 0.76375 0.85893 0.02003 0.27707 anti-human gamma-Gla 0.0006 <.0001 0.9413 0.2989
16 16 16 16 var41 0.81505 0.98466 0.12320 0.33588 anti-TF-VIIa 0.0001 <.0001 0.6494 0.2034
16 16 16 16 var42 0.90646 0.77S65 0.07917 0.20781 anti-complement C3c <.0O01 0.0004 0.7707 0.4399
16 16 16 16 var43 0.94230 0.74645 0.11691 0.27490 anti-Complement C4 <.0001 0.0009 0.6663 0.3028
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations varl6 varl7 varl8 varl9 var33 0.91899 0.99141 0.98356 0.92935 anti-BSA e.OOOl ■=.0001 <.0001 <.0001
16 16 16 16 var34 0.86813 0.91958 0.92746 0.95168 anti-LBP <.0001 <-0001 <.0001 <-0001
16 16 16 16 var35 0.53005 0.56212 0.57768 0.65004 anti-PTX3 0.0347 0.0234 0.0191 0.0064
16 16 16 16 var36 0.91241 0.95236 0.95380 0.99820 anti-complement C5 <.0001 <.0001 <.0001 <.0001
16 16 16 16 var37 0.92033 0.98065 0.99114 0.91303 anti-fibrinogen <.0001 <.0001 <.0001 <.0001
16 16 16 16 var38 0.39490 0.45461 0.51036 0.41354 anti-D-Dimer 0.1301 0.0769 0.0434 0.1113
16 16 16 16 var39 0.93118 0.98502 0.98262 0.96490 anti-factor V <.0001 <.0001 ^.0001 <.0001
16 16 16 16 var40 0.66993 0.80773 0.79686 0.66042 anti-human gamma-Gla 0.0045 0.0002 0.0002 0.0054
16 16 16 16 var41 0.73280 0.86068 0.85753 0.76957 anti-TF-VIIa 0.0012 <.0001 <.0001 0.0005
16 16 16 16 var42 0.79247 0.88242 0.86085 0.88585 anti-complement C3c 0.0003 <.0001 <-0001 <-0001
16 IS 16 16 var43 0.86S61 0.90233 0.90742 0.94065 anti-Complement C4 <.0001 <.0001 <-0001 <.0001
IS 16 16 16
Pearson Correlation Coefficients Prob > ]r| under HO: Rho=0 Number of Observations var20 var21 var22 var23 var33 0.90342 0.60755 0.34704 0.44914 anti-BSA <.0001 0.0125 0.1879 0.0809
16 16 16 16 var34 0.8S670 0.65640 0.39055 0.44007 anti-LBP <.0001 0.0057 0.1348 0.0880
16 16 16 16 var35 0.58044 0.14383 0.08254 0.14353 anti-PTX3 0.0184 0.5951 0.7612 0.5959
16 16 16 16 var36 0.89933 0.56697 0.38364 0.49407 anti-complement C5 <.0001 0.0220 0.1424 0.0518
16 16 16 16 var37 0.93873 0.67566 0.38385 0.47127 anti-fibrinogen <.0001 0.0041 0.1422 0.0654
16 16 16 16 var38 0.37579 0.62267 0.27271 0.15488 anti-D-Dimer 0.1514 0.0100 0.3068 0.5668
16 16 16 16 var39 0.92196 0.57268 0.34896 0.44512 anti-factor V <.0001 0.0204 0.1853 0.0840
16 16 16 16 var40 0.61439 0.70797 0.27382 0.31802 anti-human gamma-Gla 0.0113 0.0021 0.3048 0.2300
16 16 16 16 var41 0.73685 0.92621 0.32330 0.44440 anti-TF-VIIa 0.0011 <.0001 0.2219 0.0846
16 16 16 16 var42 0.78852 0.47473 0.51333 0.39253 anti-complement C3c 0.0003 0.0632 0.0420 0.1326
16 16 16 16 var43 0.87232 0.46987 0.58487 0.41908 anti-Complement C4 ■c.OOOl 0.0663 0.0173 0.1062
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var24 var25 var26 var27 var33 0 .8602S 0 .96413 0 .95517 0 .97225 anti-BSA <.0001 <.0001 <-0001 <.0001
16 16 16 16 var34 0 .84110 0 .93306 0 .93686 0 .92755 anti-LBP <.0001 <.0001 <-0001 <.0001
16 16 16 16 var35 0 .43600 0 .57323 0 .54811 0 .60544 anti-PTX3 0.0914 0.0203 0.0279 0.0129
16 16 16 16 var3S 0.87830 0.96503 0.95738 0.97301 anti-complement C5 <.0001 <.0001 <.0001 <.0001
IS 16 16 16 var37 0.86531 0.98412 0.97468 0.97556 anti- fibrinogen <.0001 <.0001 <.0001 <.0001
16 16 16 16 var38 0.45692 0.45509 0.50708 0.46042 anti-D-Dimer 0.0752 0.0765 0.0450 0.0727
16 16 16 16 var39 0.87408 0.97309 0.95756 0.98571 anti-factor V <.0001 <.0001 <.0001 <.0001
16 16 16 16 var40 0.65172 0.73285 0.77735 0.73723 anti-human gamma-Gla 0.0062 0.0012 0.0004 0.0011
16 16 16 16 var41 0.69826 0.84151 0.87401 0.83100 anti-TF-VIIa 0.0026 <.0001 <.0001 <.0001
16 16 16 16 var42 0.83966 0.84762 0.83824 0.87163 anti-complement C3c <.0001 <.0001 <-0001 <.0001
16 16 16 16 var43 0.93812 0.90312 0.87982 0.92579 anti-Complement C4 <.0001 <.0001 <.0001 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var28 var29 var30 var31 var33 0.15417 0.26345 0.36737 0.33736 anti-BSA 0.5686 0.3242 0.1616 0.2013
16 16 16 16 var34 0.18694 -0.01452 0.34083 0.30279 anti-LBP 0.4882 0.9574 0.1964 0.2543
16 16 16 16 var35 -0.18905 -0.14470 0.11391 0.05073 anti-PTX3 0.4832 0.5929 0.6745 0.8520
16 16 ' 16 16 var36 0.09271 -0.03140 0.43686 0.36980 anti-complement C5 0.7327 0.9081 0.0907 0.1586
16 16 16 16 var37 0.20770 0.20438 0.39787 0.38696 anti-fibrinogen 0.4402 0.4477 0.1270 0.1387
16 16 16 16 var38 0.43198 0.20193 0.13902 0.16325 anti-D-Dimer 0.0947 0.4533 0.6076 0.5458
16 16 16 16 var39 0.08346 0.14173 0.37286 0.32490 anti-factor V 0.7586 0.6006 0.1549 0.2195
16 16 16 16 var40 0.42984 0.58575 0.25350 0.27059 anti-human gamma-Gla 0.0966 0.0171 0.3435 0.3108
16 16 16 16 var41 0.40174 0.31503 0.36940 0.38484 anti-TF-VIIa 0.1230 0.2347 0.1591 0.1410 16 16 IS 16 var42 0.00173 0.10311 0 .28943 0.21567 anti-complement C3c 0.9949 0.7039 0.2769 0.4224
16 16 16 16 var43 0.02820 -0.06297 0 .31844 0.24384 anti-Complement C4 0.9174 0.8168 0.2294 0.3628
IS 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var32 var33 var34 var35 var33 -0.15118 1.00000 0.90263 0.58931 anti-BSA 0.5762 <.0001 0.0163
16 16 16 16 var34 -0.05345 0.90263 1.00000 0.59678 anti-LBP 0.8441 <.0001 0.0147
16 16 IS 16 var35 0.06710 0.58931 0.59678 1.00000 anti-PTX3 0.8050 0.0163 0.0147
16 16 16 16 var36 -0.07404 0.93879 0.95493 0.65301 anti-complement C5 0.7852 <.0001 <.0001 0.0061
16 IS 16 16 var37 -0.11429 0.97600 0.91889 0.53575 anti-fibrinogen 0.6734 <.0001 <.0001 0.0324
16 16 16 16 var38 0.25820 0.44657 0.37895 0.23044 anti-D-Dimer 0.3343 0.0829 0.1478 0.3905
16 16 16 16 var39 -0.15869 0.99072 0.92735 0.63144 anti-factor V 0.5572 <.0001 <-0001 0.0087
16 16 16 16 var40 0.05325 0.82049 0.63486 0.37297 anti-human gamma-Gla 0.8447 <.0001 0.0082 0.1548
16 16 16 16 var41 -0.04759 0.83869 0.80805 0.34345 anti-TF-VIla 0.8611 <.0001 0.0002 0.1928
16 16 16 16 var42 -0.20127 0.88805 0.83457 0.71507 anti-complement C3c 0.4548 <.0001 <.0001 0.0018
16 16 16 16 var43 -0.21857 0.90006 0.88567 0.S2157 anti-Complement C4 0.4161 <.0001 <.0001 0.0102
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var36 var37 var38 var39 var33 0.93879 0.97600 0.44657 0.99072 anti-BSA <.0001 <.0001 0.0829 <.0001
16 16 16 16 var34 0.95493 0.91889 0.37895 0.92735 anti-LBP <.0001 <.0001 0.1478 <.0001
16 16 16 16 var35 0.65301 0.53575 0.23044 0.63144 anti-PTX3 0.0061 0.0324 0.3905 0.0087
16 16 16 16 var3S 1.00000 0.92501 0.40936 0.97279 anti-complement C5 <.0001 0.1154 <.0001
16 16 16 16 var37 0.92501 1.00000 0.46319 0.96519 anti-fibrinogen <.0001 0.0708 <.0001
16 16 16 16 var38 0.40936 0.46319 1.00000 0.41347 anti-D-Dimer 0.1154 0.0708 0.1114
16 16 16 16 var39 0.97279 0.96519 0.41347 1.00000 anti-factor V <.0001 <.0001 0.1114
16 16 16 16 var40 0.66664 0.78659 0.76874 0.75882 anti-human gamma-Gla 0.0048 0.0003 0.0005 0.0007
16 16 16 16 var41 0.77644 0.87082 0.56678 0.81100 anti-TF-VIIa 0.0004 <.0001 0.0221 0.0001
16 16 16 16 var42 0.89334 0.83816 0.32588 0.90737 anti-complement C3c <.0001 <.0001 0.2180 <.0001
16 16 16 16 var43 0.94822 0.87484 0.38901 0.93446 anti-Complement C4 <.0001 <.0001 0.1364 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var40 var41 var42 var43 var33 0.82049 0.83869 0.88805 0.90006 anti-BSA <.0001 <.0001 <.0001 <.0001
16 16 16 16 var34 0.63486 0.80805 0.83457 0.88567 anti-LBP 0.0082 0.0002 <.0001 <.0001
IS 16 16 16 var35 0.37297 0.34345 0.71507 0.62157 anti-PTX3 0.1548 0.1928 0.0018 0.0102
16 16 16 16 var36 0.66664 0.77644 0.89334 0.94822 anti-complement C5 0.0048 0.0004 <.0001 <.0001
16 16 16 16 var37 0.78659 0.87082 0.83816 0.87484 anti-fibrinogen 0.0003 <.0001 <.0001 <.0001
16 16 16 16 var38 0.76874 0.56678 0.32588 0.38901 anti-D-Dimer 0.0005 0.0221 0.2180 0.1364
16 16 16 16 var39 0.75882 0.81100 0.90737 0.93446 anti-factor V 0.0007 0.0001 <.0001 <.0001
16 16 16 16 var40 1.00000 0.81907 0.66389 0.62722 anti-human gamma-Gla 0.0001 0.0050 0.0093
16 16 16 16 var41 0.81907 1.00000 0.71902 0.70038 anti-TF-VIIa 0.0001 0.0017 0.0025
16 16 16 16 var42 0.66389 0.71902 1.00000 0.93856 anti-complement C3c 0.0050 0.0017 <.0001
16 16 16 16 var43 0.62722 0.70038 0.93856 1.00000 anti-Complement C4 0.0093 0.0025 <-0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var45 var46 var47 var48 var33 0.29072 0.15395 0.74772 0.40864 anti-BSA 0.2747 0.5692 0.0009 0.1161
16 16 16 16 var34 0.33018 0.11132 0.74813 0.35477 anti-LBP 0.2117 0.6815 0.0009 0.1775
16 16 16 16 var35 0.64927 -0.13045 0.47584 -0.04070 anti-PTX3 0.0065 0.6301 0.0625 0.8810
16 16 16 16 var36 0.35092 0.18793 0.72153 0.27949 anti-complement C5 0.1826 0.4858 0.0016 0.2945
16 16 16 16 var37 0.25301 0.19027 0.74263 0.45342 anti-fibrinogen 0.3444 0.4803 0.0010 0.0777
16 16 16 16 var38 0.05855 0.13297 0.78013 0.69611 anti-D-Dimer 0.8295 0.6235 0.0004 0.0027
16 16 16 16 var39 0.33041 0.14029 0.72774 0.33326 anti-factor V 0.2113 0.6043 0.0014 0.2072
16 16 16 16 var40 0.14194 0.16294 0.81138 0.73448 anti-human gamma-Gla 0.6000 0.5466 0.0001 0.0012
16 16 16 16 var41 0.18511 0.21452 0.73364 0.75968 anti-TF-VIIa 0.4925 0.4250 0.0012 0.0006
16 16 16 16 var42 0.45420 0.02325 0.60691 0.26575 anti-complement C3c 0.0772 0.9319 0.0127 0.3198
16 16 16 16 var43 0.33075 0.06114 0.68956 0.21478 anti-Complement C4 0.2108 0.8220 0.0031 0.4244
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var49 var50 var51 var52 var33 0.51992 0.87200 0.88837 0.96626 anti-BSA 0.0390 <.0001 <.0001 <.0001
16 16 16 16 var34 0.50441 0.67004 0.76379 0.88412 anti-LBP 0.0463 0.0045 0.0006 <.0001
16 16 16 16 var35 0.02163 0.41198 0.37998 0.55529 anti-PTX3 0.9366 0.1128 0.1466 0.0256
16 16 16 16 var36 0.3945S 0.69268 0.83013 0.91143 anti-complement C5 0.1305 0.0029 <.0001 <.0001
16 16 16 16 var37 0.55054 0.80532 0.90522 0.98500 anti-fibrinogen 0.0271 0.0002 < .0001 <.0001
16 16 16 16 var38 0.52600 0.27626 0.31320 0.52780 anti-D-Dimer 0.0364 0.3003 0.2375 0.0356
16 16 16 16 var39 0.45470 0.81565 0.87686 0.95830 anti-factor V 0.0768 0.0001 <.0001 <.0001
16 16 16 16 var40 0.70812 0.82143 0.65610 0.79740 anti-human gamma-Gla 0.0021 <.0001 0.0058 0.0002
16 16 16 16 var41 0.85142 0.72116 0.73042 0.84353 anti-TF-VIIa <.0001 0.0016 0.0013 <.0001
16 16 16 16 var42 0.35818 0.74354 0.79008 0.81693 anti-complement C3c 0.1731 0.0010 0.0003 0.0001
16 16 16 16 var43 0.29904 0.65150 0.84862 0.86974 anti-Complement C4 0.2605 0.0063 <-0001 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var53 var54 var55 var56 var33 0.86924 0.27755 0.68824 0.90785 anti-BSA <.0001 0.2980 0.0032 <.0001
16 16 16 16 var34 0.83244 -0.00919 0.49047 0.71342 anti-LBP <.0001 0.9731 0.0537 0.0019
16 16 16 16 var35 0.54976 -0.13650 0.27710 0.46757 anti-PTX3 0.0274 0.6142 0.2988 0.0678
16 16 16 16 var36 0.91756 -0.04132 0.51887 0.75117 anti-complement C5 <.0001 0.8792 0.0395 0.0008
16 16 16 16 var37 0.89672 0.29448 0.64850 0.83431 anti-fibrinogen <.0001 0.2682 0.0066 <.0001
16 16 16 16 var38 0.35954 -0.06781 0.82753 0.30705 anti-D-Dimer 0.1714 0.8030 <.0001 0.2474
16 16 16 16 var39 0.89666 0.16567 0.61518 0.86289 anti-factor V <.0001 0.5398 0.0112 <.0001
16 16 16 16 var40 0.57876 0.37474 0.97648 0.83307 anti-human gamma-Gla 0.0188 0.1527 <.0001 < .0001 IS 16 16 16 var41 0.70S35 0.24541 0.71788 0. 73718 anti-TF-VIIa 0.0022 0.359S 0.0017 0.0011 16 16 16 16 var42 0.76970 0.05806 0.53149 0. 79380 anti-complement C3c 0.0005 0.8309 0.0341 0.0002 16 16 16 16 var43 0.85358 -0.05149 0.48969 0. 71406 anti-Complement C4 <.0001 0.8498 0.0542 0.0019 16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var57 var58 var59 var60 var33 0.53527 0.55006 0.76222 0.78201 anti-BSA 0.0326 0.0273 0.0006 0.0003
16 16 16 16 var34 0.63251 0.46316 0.85748 0.53727 anti-LBP 0.0086 0.0708 <.0001 0.0319
16 16 IS 16 var35 0.14443 0.00484 0.33119 0.32035 anti-PTX3 0.5936 0.9858 0.2102 0.2264
16 16 16 16 var36 0.51398 0.43449 0.73186 0.56303 anti-complement C5 0.0417 0.0926 0.0013 0.0232
16 16 16 16 var37 0.58502 0.59883 0.81129 0.70232 anti-fibrinogen 0.0173 0.0142 0.0001 0.0024
16 16 16 16 var38 0.67649 0.52808 0.50116 0.22336 anti-D-Dimer 0.0040 0.0355 0.0480 0.4057
16 16 16 16 var39 0.50527 0.49004 0.73235 0.71110 anti-factor V 0.0459 0.0540 0.0013 0.0020
16 16 16 16 var40 0.66543 0.67605 0.72507 0.78878 anti-human gamma-Gla 0.0049 0.0040 0.0015 0.0003
16 16 16 16 var41 0.81656 0.80244 0.85369 0.64375 anti-TF-VIIa 0.0001 0.0002 <.O001 0.0071
16 16 16 16 var42 0.38580 0.34488 0.62033 0.64691 anti-complement C3c 0.1400 0.1908 0.0104 0.0068
16 16 16 16 var43 0.41863 0.33310 0.62800 0.52844 anti-Complement C4 0.1066 0.2074 0.0092 0.0353
16 16 16 16
Pearson Correlation Coefficients Prob > I rI under HO : RhO=O Number of Observations var61 var62 var63 var64 var33 0.83940 0.69824 0.92123 0.97208 anti-BSA <.0001 0.0026 <.0001 <.0001
16 16 16 16 var34 0.96884 0.85277 0.90374 0.92853 anti-LBP <.0001 <.0001 <.0001 •=.0001
IS 16 16 16 var35 0.50614 0.32331 0.47699 0.66418 anti-PTX3 0.0455 0.2219 0.0617 0.0050
16 16 16 16 var36 0.88936 0.74073 0.89294 0.97863 anti-complement C5 <.0001 0.0010 < .0001 <.0001
16 16 16 16 var37 0.86365 0.75267 0.93591 0.95190 anti-fibrinogen <.0001 0.0008 <.0001 <.0001
16 16 16 16 var38 0.35988 0.54910 0.63356 0.41726 anti-D-Dimer 0.1710 0.0276 0.0084 0.1078
16 16 16 16 var39 0.85172 0.69290 0.90927 0.99274 anti-factor V <.0001 0.0029 <.0001 <.0001
16 16 16 16 var40 0.6227S 0.66267 0.85403 0.71603 anti-human gamma-Gla 0.0100 0.0052 <.O001 0.0018
16 16 16 16 var41 0.80547 0.86123 0.96038 0.78161 anti-TF-VIIa 0.0002 <.0001 <.0001 0.0003
16 16 16 16 var42 0.76154 0.60829 0.80195 0.89754 anti-complement C3c 0.0006 0.0124 0.0002 <.0001
16 16 16 16 var43 0.79138 0.63190 0.82545 0.94416 anti-Complement C4 0.0003 0.0086 <.0001 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var65 var66 var67 var68 var33 0.80125 0.85449 0.59336 0.68759 anti-BSA 0.0002 <.0001 0.0154 0.0032
16 16 16 16 var34 0.84070 0.93263 0.53830 0.67100 anti-LBP <.0O01 <.0001 0.0315 0.0044
16 16 16 16 var35 0.39887 0.48178 0.46208 0.49240 anti-PTX3 0.1259 0.0588 0.0715 0.0527
16 16 16 16 var36 0.80627 0.88826 0.58688 0.65348 anti-complement C5 0.0002 <.0001 0.0169 0.0060
16 16 16 16 var37 0.79624 0.87719 0.55732 0.67599 anti-fibrinogen 0.0002 <.0001 0.0249 0.0040
16 16 16 16 var38 0.45336 0.60729 0.22510 0.38560 anti-D-Dimer 0.0778 0.0126 0.4019 0.1402
16 16 16 16 var39 0.80551 0.85819 0.61853 0.67970 anti-factor V 0.0002 <.0001 0.0106 0.0038
16 16 16 16 var40 0.67051 0.77183 0.37484 0.57783 anti-human garama-Gla 0.0045 0.0005 0.1526 0.0191
16 16 16 16 var41 0.84864 0.91304 0.52505 0.60023 anti-TF-VIIa <.0001 <.0001 0.0368 0.0140
16 16 16 16 var42 0.67643 0.77315 0.61100 0.66437 anti-complement C3c 0.0040 0.0004 0.0119 0.0050
16 16 16 16 var43 0.72399 0.80300 0.64056 0.68247 anti-Complement C4 0.0015 0.0002 0.0075 0.0036
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var69 var70 var71 var72 var33 0.00431 0.63168 0.63974 0.88551 anti-BSA 0.9874 0.0087 0.0076 <.0001
16 16 16 16 var34 0.00817 0.56866 0.60927 0.82439 anti-LBP 0.9760 0.0215 0.0122 <.0001
16 16 16 16 var35 -0.01213 0.16099 0.15738 0.40197 anti-PTX3 0.9644 0.5514 0.5605 0.1227
16 16 16 16 var36 0.01906 0.52190 0.56091 0.79553 anti-complement C5 0.9441 0.0381 0.0238 0.0002
16 16 16 16 var37 -0.01488 0.66884 0.66114 0.92486 anti-fibrinogen 0.9564 0.0046 0.0053 <.0001
16 16 16 16 var38 -0.06376 0.52937 0.60600 0.55741 anti-D-Dimer 0.8145 0.0350 0.0128 0.0249
16 16 16 16 var39 0.01856 0.58468 0.60159 0.84468 anti-factor V 0.9456 0.0174 0.0137 <.0001
16 16 16 16 var40 -0.03795 0.71784 0.74462 0.84932 anti-human gamma-Gla 0.8890 0.0017 0.0009 <.0001
16 16 16 16 var41 0.03180 0.92170 0.92003 0.92626 anti-TF-VIIa 0.9069 •s.OOOl <.0001 <.0001
16 16 16 16 var42 0.00912 0.49813 0.49451 0.77917 anti-complement C3c 0.9732 0.0496 0.0515 0.0004
16 16 16 16 var43 0.03521 0.45243 0.48240 0.75966 anti-Complement C4 0.8970 0.0785 0.0584 0.0006
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var74 var75 var76 var77 var33 0.49700 0.65905 0.65121 0.49786 anti-BSA 0.0502 0.0055 0.0063 0.0497 16 16 16 16 var34 0.47641 0.53106 0.52236 0.39315 anti-LBP 0.0621 0.0343 0.0379 0.1319
16 16 16 16 var35 0.00462 0.10186 0.08856 -0.03366 anti-PTX3 0.9864 0.7074 0.7443 0.9015
16 16 16 16 var36 0.38484 0.47475 0.46956 0.37564 anti-complement C5 0.1411 0.0631 0.0665 0.1516
16 16 16 16 var37 0.56197 0.67289 0.67125 0.54232 anti-fibrinogen 0.0235 0.0043 0.0044 0.0300
16 16 16 16 var38 0.59716 0.57319 0.56879 0.38141 anti-D-Dimer 0.0146 0.0203 0.0215 0.1449
16 16 16 16 var39 0.43122 0.57358 0.56694 0.44786 anti-factor V 0.0954 0.0202 0.0220 0.0819
16 16 16 16 var40 0.70504 0.85909 0.84900 0.54431 anti-human gamma-Gla 0.0023 <.0001 <.0001 0.0293
16 16 16 16 var41 0.86168 0.86838 0.87437 0.71124 anti-TF-VIIa <.0001 <.0001 <.0001 0.0020
16 16 16 16 var42 0.35303 0.47794 0.48662 0.27216 anti-complement C3c 0.1798 0.0611 0.0559 0.3079
16 16 16 16 var43 0.30614 0.40103 0.40507 0.29781 anti-Complement C4 0.2488 0.1237 0.1196 0.2626
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var78 var79 var80 varδl var33 0.80448 0.38975 0.58989 0.65310 anti-BSA 0.0002 0.1356 0.0162 0.0155
16 16 16 13 var34 0.73783 0.32359 0.53765 0.66785 anti-LBP 0.0011 0.2215 0.0317 0.0126
16 16 16 13 var35 0.39892 -0.06996 0.06518 0.29302 anti-PTX3 0.1259 0.7968 0.8105 0.3313
16 16 16 13 var36 0.78821 0.26490 0.46234 0.63759 anti-complement C5 0.0003 0.3214 0.0714 0.0191
16 16 16 13 var37 0.86844 0.45077 0.63870 0.76235 anti- fibrinogen <.0001 0.0797 0.0077 0.0024
16 16 16 13 var38 0.28150 0.74801 0.63416 0.19901 anti-D-Dimer 0.2909 0.0009 0.0083 0.5145
16 16 16 13 var39 0.80386 0.31572 0.52141 0.66136 anti- factor V 0.0002 0.2336 0.0383 0.0138
16 16 16 13 var40 0.53796 0.72491 0.78562 0.34493 anti-human gamma-Gla 0.0316 0.0015 0.0003 0.2484
16 16 16 13 var41 0.69320 0.75803 0.89735 0.53899 anti-TF-VIIa 0.0029 0.0007 <.0001 0.0573
16 16 16 13 var42 0.S3578 0.22022 0.42259 0.48653 anti-complement C3c 0.0081 0.4125 0.1030 0.0918
16 16 16 13 var43 0.71350 0.19494 0.38563 0.62413 anti-Complement C4 0.0019 0.4694 0.1402 0.0226
16 16 16 13
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var82 var83 var84 var85 var33 0.58045 0.86594 0.85353 0.64343 anti-BSA 0.0375 0.0001 0.0002 0.0177
13 13 13 13 var34 0.55573 0.71543 0.69032 0.45952 anti-LBP 0.0486 0.0060 0.0090 0.1142
13 13 13 13 var35 0.19015 0.32627 0.37546 0.07151 antl-PTX3 0.5338 0.2766 0.2062 0.8164
13 13 13 13 var36 0.54224 0.69328 0.66693 0.44041 anti-complement C5 0.0556 0.0086 0.0128 0.1320
13 13 13 13 var37 0.58882 0.83978 0.78811 0.64893 anti-fibrinogen 0.0342 0.0003 0.0014 0.0164
13 13 13 13 var38 0.78195 0.57381 0.24142 0.59641 anti-D-Dxmer 0.0016 0.0403 0.4268 0.0314
13 13 13 13 var39 0.55451 0.79934 0.79374 0.55462 anti-factor V 0.0492 0.0010 0.0012 0.0492
13 13 13 13 var40 0.77606 0.96451 0.81173 0.89335 anti-human gamma-Gla 0.0018 <.0001 0.0008 <.0001
13 13 13 13 var41 0.76995 0.89006 0.73386 0.84841 anti-TF-VIIa 0.0021 <.0001 0.0043 0.0002
13 13 13 13 var42 0.44387 0.69609 0.71876 0.47375 anti-complement C3c 0.1287 0.0082 0.0056 0.1020
13 13 13 13 var43 0.48573 0.63333 0.61974 0.38410 anti-Complement C4 0.0924 0.0201 0.0239 0.1951
13 13 13 13
Pearson Correlation Coefficients Prob > J 271 under HO: Rho=0 Number of Observations var86 var87 var88 var89 var33 0.38276 0.50955 0.31852 0.97706 anti-BSA 0.1434 0.0524 0.2473 <.0001
16 15 15 15 var34 0.38397 0.35263 0.21694 0.83898 anti-LBP 0.1420 0.1974 0.4374 <.0001
16 15 15 15 var35 0.04561 0.08464 0.09773 0.56450 anti-PTX3 0.8668 0.7642 0.7290 0.0284
16 15 15 IS var36 0.29887 0.38895 0.19603 0.88780 anti-complement C5 0.2608 0.1519 0.4838 <.0001
16 15 15 15 var37 0.38401 0.47218 0.44464 0.91610 anti-fibrinogen 0.1420 0.0755 0.0968 <.0001
16 15 15 15 var38 0.40341 0.58521 0.05425 0.37059 anti-D-Dimer 0.1213 0.0219 0.8477 0.1739
16 15 15 15 var39 0.33880 0.46107 0.28806 0.95906 anti-factor V 0.1993 0.0837 0.2978 <.0001
16 15 15 15 var40 0.54724 0.75446 0.15603 0.82665 anti-human gamma-Gla 0.0282 0.0012 0.5787 0.0001
16 15 15 15 var41 0.74193 0.77645 0.25603 0.79502 anti-TF-VIIa 0.0010 0.0007 0.3570 0.0004
16 15 15 15 var42 0.26176 0.43135 0.08840 0.88031 anti-complement C3c 0.3274 0.1084 0.7541 <.0001
16 15 15 15 var43 0.21049 0.34784 0.18804 0.84804 anti-Complement C4 0.4339 0.2039 0.5022 <.0001
16 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var90 var91 var92 var93 var33 0.87849 0.93609 0.92807 0.95257 anti-BSA <.0001 <.0001 <.0001 <.0001
15 15 16 16 var34 0.86538 0.94676 0.72969 0.94057 anti-LBP <.0001 <.0001 0.0013 <.0001
15 15 16 16 var35 0.60007 0.49530 0.43441 0.66225 anti-PTX3 0.0180 0.0605 0.0927 0.0052
15 15 16 16 var36 0.96074 0.92961 0.76278 0.99433 anti-complement C5 <.0001 <.0001 0.0006 <.0001
15 15 16 16 var37 0.85235 0.93565 0.87988 0.93529 ant i - f ibr inogen <.0001 <.0001 <-0001 <.0001
15 15 16 16 var38 0.37928 0.42820 0.33103 0.42358 anti-D-Dimer 0.1632 0.1113 0.2104 0.1021
15 15 16 16 var39 0.91863 0.93554 0.88277 0.98343 anti- factor V ■=.0001 <.0001 <.0001 <.0001 15 15 ie 16 var40 0.S0794 0.75267 0.83115 0.68543 anti-human gamma-Gla 0.0152 0.0012 <.0001 0.0034
15 15 16 16 var41 0.68118 0.89318 0.79922 0.77315 anti-TF-VIIa 0.0052 <.0001 0.0002 0.0004
15 15 IS 16 var42 0.83233 0.81371 0.77212 0.89769 anti-complement C3c 0.0001 0.0002 0.0005 <.0001
15 15 16 16 var43 0.89750 0.84086 0.72378 0.95311 anti-Complement C4 <.0001 <.0001 0.0015 <.0001
15 15 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
Capture varl var2 var3 var45 0.03495 0.15964 0.29020 0.30545 anti-Annexin V 0.8977 0.5548 0.2756 0.2500
16 16 16 16 var46 0.21956 0.26315 0.23719 0.19732 anti-Lipid A 0.4139 0.3248 0.3764 0.4639
16 16 16 16 var47 0.55360 0.67480 0.76636 0.70764 anti-isopeptide bond 0.0261 0.0041 0.0005 0.0022
16 16 16 16 var48 0.79115 0.83565 0.41706 0.31431 anti-vitronectin 0.0003 <.0001 0.1080 0.2358
16 16 16 16 var49 0.94414 0.91683 0.52135 0.42238 anti-thrombin <.0001 <-0001 0.0384 0.1031
16 16 16 16 var50 0.72244 0.75733 0.75291 0.73235 anti-osteocalcin 0.0016 0.0007 0.0008 0.0013
16 16 16 16 var51 0.57268 0.64825 0.87832 0.90882 anti-Troponin T 0.0204 0.0066 <.0001 <.0001
16 16 16 16 var52 0.63099 0.75103 0.96176 0.97582 anti-vimentin 0.0088 0.0008 <.0001 <.0001
16 16 16 16 var53 0.43379 0.59600 0.92297 0.94925 a-tropomyosin 0.0932 0.0148 <.0001 <.0001
16 16 16 16 var54 0.48395 0.36530 0.10316 0.15254 anti-HSA 0.0575 0.1641 0.7038 0.5728
16 16 16 16 var55 0.64933 0.74974 0.62637 0.54707
Troponin I cardiac 0.0065 0.0008 0.0094 0.0283
16 16 16 16
Pearson Correlation Coefficients Prob > I rI under HO : Rho=0 Number of Observations var4 var5 var6 var7 var45 0.31538 -0.14667 0.10421 0.06172 anti-Annexin V 0.2341 0.5878 0.7009 0.8204
16 16 iε 16 var4S 0.20853 0.73822 0.25282 0.86477 anti-Lipid A 0.4383 0.0011 0.3448 ■c.OOOl
16 16 16 16 var47 0.74546 0.43452 0.57691 0.19175 anti-isopeptide bond 0.0009 0.0926 0.0193 0.4768
16 16 16 16 var48 0.35799 0.69951 0.87166 0.09382 anti-vitronectin 0.1734 0.0026 <.0001 0.7296
16 16 16 16 var49 0.46083 0.60215 0.93105 0.08564 anti-thrombin 0.0724 0.0136 <.0001 0.7525
16 16 16 16 var50 0.74009 0.42892 0.49309 0.28445 anti-osteocalcin 0.0010 0.0974 0.0523 0.2856
16 16 16 16 varSl 0.89003 0.46340 0.50840 0.56279 anti-Troponin T <.0001 0.0706 0.0443 0.0232
16 16 16 16 var52 0.97125 0.36698 0.61073 0.37175 anti-vimentin <.0001 0.1621 0.0120 0.1562
16 16 16 16 var53 0.93901 0.39691 0.47832 0.69094 a-tropomyosin <.0001 0.1280 0.0609 0.0030
16 16 16 16 var54 0.10624 0.30313 0.21445 -0.07686 anti-HSA 0.6954 0.2538 0.4251 0.7772
16 16 16 16 var55 0.59234 0.63205 0.59726 0.16578
Troponin I cardiac 0.0156 0.0086 0.0146 0.5395
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rh.o=0 Number of Observations var8 var9 varlO varll var45 0.03383 0.32514 0.31803 -0.16726 anti-Annexin V 0.9010 0.2191 0.2300 0.5358
16 16 16 16 var46 0.78915 0.14419 0.20798 0.22172 anti-Lipid A 0.0003 0.5942 0.4396 0.4092
16 16 16 16 var47 0.44063 0.75133 0.72932 0.43601 anti-isopeptide bond 0.0876 0.0008 0.0013 0.0914
16 16 16 16 var48 0.55368 0.37987 0.33594 0.75698 anti-vitronectin 0.0261 0.1467 0.2033 0.0007
16 16 16 16 var49 0.57969 0.49640 0.44806 0.74985 anti-thrombin 0.0186 0.0505 0.0818 0.0008
16 16 16 16 var50 0.48975 0.82780 0.74625 0.51525 anti-osteocalcin 0.0542 <.0001 0.0009 0.0411
16 16 16 16 var51 0.68347 0.86965 0.89152 0.16622 anti-Troponin T 0.0035 <.0001 <.0001 0.5384
16 16 16 16 var52 0.S0284 0.959Ξ1 0.96673 0.22668 ant i - vitnent in 0.0134 <.0001 ■=.0001 0.3985
16 16 16 16 var53 0.73244 0.88444 0.94098 -0.00729 a-tropomyosin 0.0013 <.0001 <.0001 0.9786
16 16 16 16 varS4 0.23078 0.17287 0.11055 0.51270 anti-HSA 0.3898 0.5220 0.6836 0.0423
IS 16 16 16 var55 0.43852 0.65086 0.57397 0.66477
Troponin I cardiac 0.0893 0.0063 0.0201 0.0050
IS 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations varl2 varl3 varl4 varlδ var45 0.33641 0.22438 -0.06278 -0.21443 anti-Annexin V 0.2027 0.4035 0.8173 0.4252
16 16 16 16 var46 0.13863 0.20930 0.91176 0.87709 anti-Lipid A 0.6086 0.4366 <.0001 <.0001
16 16 16 16 var47 0.75109 0.74007 -0.00820 0.25678 anti-isopeptide bond 0.0008 0.0010 0.9759 0.3370
16 16 16 16 var48 0.34627 0.71016 0.03253 0.23233 anti-vitronectin 0.1889 0.0021 0.9048 0.3866
16 16 16 16 var49 0.45538 0.81796 0.00259 0.23144 anti-thrombin 0.07S3 0.0001 0.9924 0.3884
16 16 16 16 var50 0.78830 0.82512 0.06330 0.21895 anti-osteocalσin 0.0003 <.0001 0.8158 0.4152
16 16 16 16 var51 0.86583 0.77849 0.33714 0.49767 anti-Troponin T <.0001 0.0004 0.2016 0.0498
16 16 16 16 var52 0.95919 0.87891 0.10145 0.28965 anti-vimentin <.0001 <.0001 0.7085 0.2765
16 16 16 16 var53 0.89977 0.73528 0.45892 0.53804 a-tropomyosin <.0001 0.0012 0.0738 0.0316
16 16 16 16 var54 0.11732 0.31116 -0.10351 -0.03914 anti-HSA 0.6652 0.2408 0.7028 0.8856
16 16 16 16 var55 0.62440 0.75163 -0.02055 0.25511
Troponin I cardiac 0.0097 0.0008 0.9398 0.3403
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rh.o=0 Number of Observations varl6 varl7 varlδ varl9 var45 0.23453 0.27476 0.28198 0.35948 anti-Annexin V 0.3819 0.3031 0.2900 0.1715
16 16 16 16 var46 0.30727 0.24720 0.18215 0.22513 anti-Lipid A 0.2470 0.3560 0.4996 0.4018
16 16 16 16 var47 0.63315 0.74875 0.77357 0.72003 anti-isopeptide bond 0.0085 0.0008 0.0004 0.0017
16 16 16 16 var48 0.26150 0.43840 0.42833 0.28133 anti-vitronectin 0.3279 0.0894 0.0979 0.2912
16 16 16 16 var49 0.36389 0.54486 0.51891 0.39417 anti-thrombin 0.1659 0.0291 0.0394 0.1309
16 16 16 16 var50 0.69980 0.84959 0.78341 0.68151 anti-osteocalcin 0.0025 <.0001 0.0003 0.0036
16 16 16 16 var51 0.89864 0.90391 0.89368 0.82222 anti-Troponin T <.0001 <.0001 <.0001 <.0001
16 16 16 16 var52 0.92978 0.95897 0.98978 0.89904 ant i - viiπent in <.0001 <.0001 <.0001 <.0001
16 16 16 16 var53 0.91169 0.89930 0.91148 0.91950 a-tropomyosin <-0001 <.0001 <.0001 <.0001
16 16 16 16 var54 0.16219 0.23649 0.20430 -0.06604 anti-HSA 0.5484 0.3779 0.4479 0.8080
16 16 16 16 var55 0.52854 0.67429 0.66347 0.51565
Troponin I cardiac 0.0353 0.0042 0.0051 0.0409
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var20 var21 var22 var23 var45 0.30347 0.14157 -0.02318 0.03432 anti-Annexin V 0.2532 0.6010 0.9321 0.8996
16 16 16 16 var46 0.07759 0.24338 0.12040 0.81032 anti-Lipid A 0.7752 0.3637 0.6569 0.0001
16 16 16 16 var47 0.64043 0.67953 0.37343 0.31643 anti-isopeptide bond 0.0075 0.0038 0.1542 0.2325
16 16 16 16 var48 0.23912 0.89086 0.22206 0.26387 anti-vitronectin 0.3724 <.0001 0.4085 0.3234
16 16 16 16 var49 0.32529 0.93764 0.17383 0.31423 anti-thrombin 0.2189 <.0001 0.5197 0.2359
16 16 16 16 var50 0.62551 0.49789 0.21688 0.39226 anti-osteocalcin 0.0096 0.0497 0.4198 0.1329
16 16 16 16 var51 0.86467 0.49407 0.52676 0.61892 anti-Troponin T <.0001 0.0517 0.0360 0.0106
16 16 16 16 var52 0.96273 0.64028 0.33094 0.40017 anti-vimentin <.0001 0.0075 0.2106 0.1246
16 16 16 16 var53 0.91554 0.49335 0.34213 0.63373 a-tropomyosin <.0001 0.0521 0.1946 0.0084
16 16 16 16 var54 0.18158 0.13307 -0.09464 0.04480 anti-HSA 0.5009 0.6232 0.7274 0.8691
16 16 16 16 var55 0.45481 0.65958 0.24944 0.25135
Troponin I cardiac 0.0767 0.0054 0.3515 0.3477
16 16 16 16
Pearson Correlation Coefficients Prob > |r] under HO: Rho=0 Number of Observations var24 var25 var26 var27 var45 0.18753 0.29354 0.26701 0.30991 anti-Annexin V 0.4868 0.2698 0.3175 0.2428
16 16 16 16 var46 0.10917 0.25829 0.30156 0.20321 anti-Lipid A 0.6873 0.3341 0.2564 0.4503
16 16 16 16 var47 0.73097 0.72439 0.75436 0.73183 anti-isopeptide bond 0.0013 0.0015 0.0007 0.0013
16 16 16 16 var48 0.29990 0.38558 0.46756 0.35658 anti-vitronectin 0.2591 0.1402 0.0678 0.1752
16 16 16 16 var49 0.35097 0.48041 0.55695 0.45813 anti-thrombin 0.1826 0.0596 0.0250 0.0743
16 16 16 16 var50 0.62911 0.74082 0.76214 0.74109 anti-osteocalcin 0.0090 0.0010 0.0006 0.0010
16 16 16 16 var51 0.86729 0.90336 0.87233 0.89602 anti-Troponin T <.0001 <.0001 <.0001 <.0001
16 16 16 16 var52 0.85371 0.97463 0.94907 0.97795 anti-vimentin <.0001 <.0001 <.0001 <.0001
16 16 16 16 var53 0.82281 0.95139 0.91751 0.94240 a-tropomyosin <.0001 <.0001 <.0001 <.0001
16 16 16 16 var54 0.02942 0.15948 0.14194 0.13294 anti-HSA 0.9139 0.5552 0.6000 0.6236
16 16 16 16 var55 0.54073 0.58716 0.64760 0.59109
Troponin I cardiac 0.0306 0.0168 0.0067 0.0159
16 16 16 16 Pearson. Correlation Coefficients Prob > |r| under HO: Rho=0 ' Number of Observations var28 var29 var30 var31 var45 -0.16207 -0.15529 0.03930 0.00522 anti-Annexin V 0.5487 0.5658 0.8851 0.9847
16 16 16 16 var46 0.62380 0.19585 0.91040 0.91505 anti-Lipid A 0.0098 0.4673 <.0001 <.0001
16 16 16 16 var47 0.37651 0.18601 0.17721 0.19549 anti-isopeptide bond 0.1506 0.4904 0.5115 0.4681
16 16 16 16 var48 0.67969 0.53903 0.20989 0.29548 anti-vitronectin 0.0038 0.0312 0.4353 0.2665
16 16 16 16 var49 0.62362 0.53210 0.21456 0.28601 anti-thrombin 0.0098 0.0339 O.4249 0.2829
16 16 16 16 varSO 0.27241 0.66159 0.29931 0.29635 anti-osteocalcin 0.3074 0.0053 0.2601 0.2651
16 16 16 16 var51 0.16820 0.20016 0.53798 0.51459 anti-Troponin T 0.5335 0.4573 0.0316 0.0414
16 16 16 16 var52 0.12842 0.15670 0.34163 0.33011 anti-vimentin 0.6355 0.5622 0.1953 0.2118
16 16 16 16 var53 0.12246 -0.06106 0.63377 0.58898 a-tropomyosin 0.6514 0.8223 0.0084 0.0164
16 16 16 16 var54 0.17927 0.76639 0.01292 0.11505 anti-HSA 0.5065 0.0005 0.9621 0.6714
16 16 16 16 var55 0.49238 0.64050 0.18810 0.21661
Troponin I cardiac 0.0527 0.0075 0.4854 0.4204
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var32 var33 var34 var35 var45 0.21549 0.29072 0.33018 0.64927 anti-Annexin V 0.4228 0.2747 0.2117 0.0065
16 16 16 16 var46 0.32752 0.15395 0.11132 -0.13045 anti-Lipid A 0.2156 0.5692 0.6815 0.6301
16 16 16 16 var47 0.09473 0.74772 0.74813 0.47584 anti-isopeptide bond 0.7271 0.0009 0.0009 0.0625
16 16 16 16 var48 0.26500 0.40864 0.35477 -0.04070 anti-vitronectin 0.3213 0.1161 0.1775 0.8810
16 16 16 16 var49 0.10982 0.51992 0.50441 0.02163 anti-thrombin 0.6856 0.0390 0.0463 0.9366
16 16 16 16 var50 0.11374 0.87200 0.67004 0.41198 anti-osteocalcin 0.6749 < .0001 0.0045 0.1128
IS 16 16 16 var51 0.29282 0.88837 0.76379 0.37998 anti-Troponin T 0.2711 <.0001 0.0006 0.1466
16 16 16 16 var52 0.15691 0.96626 0.88412 0.55529 anti-vimentin 0.5617 <.0001 <.0001 0.0256
16 16 16 16 var53 0.05715 0.86924 0.83244 0.54976 a-tropomyosin 0.8335 <.0001 <.0001 0.0274
16 16 16 16 var54 0.20487 0.27755 -0.00919 -0.13650 anti-HSA 0.4466 0.2980 0.9731 0.6142
16 16 16 16 var55 0.13109 0.68824 0.49047 0.27710
Troponin I cardiac 0.6284 0.0032 0.0537 0.2988
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var36 var37 var38 var39 var45 0.35092 0.25301 0.05855 0.33041 anti-Annexin V 0.1826 0.3444 0.8295 0.2113
16 16 16 16 var46 0.18793 0.19027 0.13297 0.14029 anti-Lipid A 0.4858 0.4803 0.6235 0.6043
16 16 16 16 var47 0.72153 0.74263 0.78013 0.72774 anti-isopeptide bond 0.0016 0.0010 0.0004 0.0014
16 16 16 16 var48 0.27949 0.45342 0.69611 0.33326 anti-vitronectin 0.2945 0.0777 0.0027 0.2072
16 16 16 16 var49 0.39455 0.55054 0.52600 0.45470 anti-thrombin 0.1305 0.0271 0.0364 0.0768
16 16 16 16 var50 0.69268 0.80532 0.27626 0.81565 anti-osteocalcin 0.0029 0.0002 0.3003 0.0001
16 16 16 16 varδl 0.83013 0.90522 0.31320 0.87686 anti-Troponin T <-0001 <.0001 0.2375 <.0001
16 16 16 16 var52 0.91143 0.98500 0.52780 0.95830 anti-vimentin <.0001 <.0001 0.0356 <.0001
16 16 16 16 var53 0.91756 0.89672 0.35954 0.89666 a-tropomyosin <.0001 <.0001 0.1714 <.0001
16 16 16 16 var54 -0.04132 0.29448 -0.06781 0.16567 anti-HSA 0.8792 0.2682 0.8030 0.5398
16 16 16 16 var55 0.51887 0.64850 0.82753 0.61518
Troponin I cardiac 0.0395 0.0066 <.0001 0.0112
16 16 16 16 Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var40 var41 var42 var43 var45 0.14194 0.18511 0.45420 0.33075 anti-Annexin V O.SOOO 0.4925 0.0772 0.2108
16 16 16 16 var46 0.16294 0.21452 0.02325 0.06114 anti-Lipid A 0.5466 0.4250 0.9319 0.8220
16 16 16 16 var47 0.81138 0.73364 0.60691 0.68956 anti-isopeptide bond 0.0001 0.0012 0.0127 0.0031
16 16 16 16 var48 0.73448 0.75968 0.26575 0.21478 anti-vitronectin 0.0012 0.0006 0.3198 0.4244
16 16 16 16 var49 0.70812 0.85142 0.35818 0.29904 anti-thrombin 0.0021 <.0001 0.1731 0.2605
16 16 16 16 var50 0.82143 0.72116 0.74354 0.65150 anti-osteocalcin <.0001 0.0016 0.0010 0.0063
16 16 16 16 var51 0.65610 0.73042 0.79008 0.84862 anti-Troponin T 0.0058 0.0013 0.0003 <.0001
16 16 16 16 var52 0.79740 0.84353 0.81693 0.86974 anti-vimentin 0.0002 <-0001 0.0001 <.0001
16 16 IS 16 var53 0.57876 0.70635 0.76970 0.85358 a-tropomyosin 0.0188 0.0022 0.0005 <.0001
IS 16 IS 16 var54 0.37474 0.24541 0.05806 -0.05149 anti-HSA 0.1527 0.3596 0.8309 0.8498
IS IS 16 16 var55 0.97648 0.71788 0.53149 0.48969
Troponin I cardiac <.0001 0.0017 0.0341 0.0542
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var45 var46 var47 var48 var45 1.00000 -0.12563 0.12452 0.09626 anti-Annexin V 0.6429 0.6459 0.7229
16 16 16 16 var46 -0.12563 1.00000 0.02688 0.22142 anti-Lipid A 0.6429 0.9213 0.4099
16 16 16 16 var47 0.12452 0.02688 1.00000 0.59404 anti-isopeptide bond 0.6459 0.9213 0.0152
16 16 16 16 var48 0.09626 0.22142 0.59404 1.00000 anti-vitronectin 0.7229 0.4099 0.0152
16 16 16 16 var49 0.05695 0.17708 0.59518 0.91522 anti-thrombin 0.8341 0.5118 0.0150 <.0001 is 16 16 16 var50 0.18778 0.14749 0.56697 0.44630 anti-osteocalcin 0.4862 0.5857 0.0220 0.0831
16 16 16 16 var51 0.08085 0.36982 0.56831 0.28973 anti-Troponin T 0.7660 0.1586 0.0216 0.2764
16 16 16 16 var52 0.26721 0.15026 0.75770 0.43249 anti-vimentin 0.3171 0.5786 0.0007 0.0943
16 16 16 16 var53 0.27179 0.41915 0.58532 0.22018 a-tropomyosin 0.3085 0.1061 0.0172 0.4125
16 16 16 16 var54 0.16048 0.06397 0.00095 0.28226 anti-HSA 0.5527 0.8139 0.9972 0.2895
16 IS 16 16 var55 0.08578 0.14572 0.77735 0.76198
Troponin 1 cardiac 0.7521 0.5902 0.0004 0.0006
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var49 var50 varδl var52 var45 0.05695 0.18778 0.08085 0.26721 anti-Annexin V 0.8341 0.4862 0.7660 0.3171
16 16 16 16 var46 0.17708 0.14749 0.36982 0.15026 anti-Lipid A 0.5118 0.5857 0.1586 0.5786
16 16 16 16 var47 0.59518 0.56697 0.56831 0.75770 anti-isopeptide bond 0.0150 0.0220 0.0216 0.0007
16 16 16 16 var48 0.91522 0.44630 0.28973 0.43249 anti-vitronectin <.0001 0.0831 0.2764 0.0943
16 16 16 16 var49 1.00000 0.56848 0.37016 0.50507 anti-thrombin 0.0216 0.1582 0.0460
16 16 16 16 var50 0.56848 1.00000 0.74202 0.76126 anti-osteocalcin 0.0216 0.0010 0.0006
16 16 16 16 var51 0.37016 0.74202 1.00000 0.88880 anti-Troponin T 0.1582 0.0010 <.0001
16 16 16 16 var52 0.50507 0.76126 0.88880 1.00000 anti-vimentin 0.0460 0.0006 <.0001
16 16 16 16 var53 0.28425 0.60012 0.89967 0.89882 a-tropomyosin 0.2860 0.0140 <.0001 <.0O01
16 16 16 16 var54 0.31134 0.57724 0.34221 0.27318 anti-HSA 0.2405 0.0192 0.1945 0.3060
16 16 16 16 var55 0.69199 0.73051 0.51562 0.66712
Troponin I cardiac 0.0030 0.0013 0.0409 0.0048
16 16 16 16 Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var53 var54 var55 var56 var45 0.27179 -0.16048 0.08578 0.22451 anti-Annexin V 0.3085 0.5527 0.7521 0.4032
16 16 16 16 var46 0.41915 0.06397 0.14572 0.12790 anti-Lipid A 0.1061 0.8139 0.5902 0.6369
16 16 16 16 var47 0.58532 0.00095 0.77735 0.60112 anti-isopeptide bond 0.0172 0.9972 0.0004 0.0138
16 16 16 16 var48 0.22018 0.28226 0.76198 0.42181 anti-vltronectin 0.4125 0.2895 0.0006 0.1037
16 16 16 16 var49 0.28425 0.31134 0.69199 0.54438 anti-thrombin 0.2860 0.2405 0.0030 0.0292
16 16 16 16 var50 0.60012 0.57724 0.73051 0.99383 anti-osteocalcin 0.0140 0.0192 0.0013 <.0001
16 16 16 16 var51 0.89967 0.34221 0.51562 0.76602 anti-Troponin T <-0001 0.1945 0.0409 0.0005
16 16 16 16 var52 0.89882 0.27318 0.66712 0.80044 anti-vimentin <.0001 0.3060 0.0048 0.0002
16 16 16 16 var53 1.00000 0.07559 0.42358 0.64886 a-tropomyosin 0.7808 0.1021 0.0065
16 16 16 16 var54 0.07559 1.00000 0.35216 0.50657 anti-HSA 0.7808 0.1810 0.0452
16 16 16 16 var55 0.42358 0.35216 1.00000 0.73409
Troponin I cardiac 0.1021 0.1810 0.0012
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var57 var58 var59 var60 var45 0.09029 -0.03494 0.14438 0.14086 anti-Annexin V 0.7395 0.8978 0.5937 0.6028
16 16 16 16 var46 0.19281 0.47730 0.24193 0.12904 anti-Lipid A 0.4743 0.0615 0.3667 0.6339
16 16 16 16 var47 0.74525 0.52047 0.76952 0.47664 anti-isopeptide bond 0.0009 0.0387 0.0005 0.0620
16 16 16 16 var48 0.82139 0.77267 0.67235 0.44203 anti-vitronectin <.0001 0.0005 0.0043 0.0865
16 16 16 16 var49 0.90037 0.85767 0.77875 0.55361 anti-thrombin <.0001 <.0001 0.0004 0.0261
16 16 16 16 var50 0.41239 0.54216 0.67755 0.98509 anti-osteocalcin 0.1124 0.0300 0.0039 <.0001
IS 16 16 16 var51 0.37751 0.55753 0.62568 0.65645 anti-Troponin T 0.1494 0.0248 0.0095 0.0057
16 16 16 16 var52 0.55998 0.57185 0.74075 0.65942 anti-vimentin 0.0241 0.0206 0.0010 0.0055
IS 16 16 16 var53 0.38928 0.47978 0.61047 0.47741 a-tropomyosin 0.1361 0.0600 0.0120 0.0615
16 16 16 16 var54 0.00485 0.34553 0.17747 0.66249 anti-HSA 0.9858 0.1899 0.5108 0.0052
16 16 16 16 var55 0.65616 0.65347 0.S5002 0.71871
Troponin I cardiac 0.0058 0.0060 0.0064 0.0017
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : RhO=O Number of Observations var61 var62 var63 var64 var45 0.26632 0.13746 0.25776 0.35195 anti-Annexin V 0.3188 0.6117 0.3351 0.1813
16 16 16 16 var46 0.22113 0.25363 0.21299 0.09194 anti-Lipid A 0.4105 0.3432 0.4284 0.7349
16 16 16 16 var47 0.72819 0.75958 0.83471 0.72862 anti-isopeptide bond 0.0014 0.0006 <.0001 0.0014
16 16 16 16 var48 0.43197 0.67371 0.65991 0.28297 anti-vitronectin 0.0947 0.0042 0.0054 0.2883
16 16 16 16 var49 0.58615 0.76213 0.74300 0.39656 anti-thrombin 0.0170 0.0006 0.0010 0.1283
16 16 16 16 var50 0.66931 0.53327 0.74455 0.75026 anti-osteocalcin 0.0046 0.0334 0.0009 0.0008
16 16 16 16 var51 0.70345 0.56034 0.78936 0.85461 anti-Troponin T 0.0024 0.0240 0.0003 <.0001
16 16 16 16 var52 0.79713 0.69132 0.92184 0.95719 anti-vimentin 0.0002 0.0030 <.0001 <-0001
16 16 16 16 var53 0.75866 0.60527 0.80495 0.90426 a-tropomyosin 0.0007 0.0130 0.0002 <.0001
16 16 16 16 var54 0.00430 -0.04395 0.13738 0.09619 anti-HSA 0.9874 0.8716 0.6119 0.7230
16 16 16 16 var55 0.49752 0.58590 0.75189 0.56752
Troponin I cardiac 0.0499 0.0171 0.0008 0.0219 16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var65 var66 var67 var68 var45 0.40772 0.23719 0.15609 0.03199 anti-Annexin V 0.1170 0.3764 0.5638 0.9064
16 16 16 16 var46 0.19440 0.20832 -0.11290 -0.14114 anti-Lipid A 0.4706 0.4388 0.6772 0.6021
16 16 16 16 var47 0.72196 0.83543 0.44538 0.68313 anti-isopeptide bond 0.0016 <.0001 0.0838 0.0035
16 16 16 16 var48 0.59588 0.61899 0.09024 0.25463 anti-vitronectin 0.0149 0.0106 0.7396 0.3412
16 16 16 16 var49 0.73715 0.70252 0.32675 0.44265 anti-thrombin 0.0011 0.0024 0.2167 0.0860
16 16 16 16 var50 0.64325 0.65150 0.40296 0.58801 anti-osteocalcin 0.0072 0.0063 0.1217 0.0166
16 16 16 16 var51 0.63022 0.69992 0.54828 0.57999 anti-Troponin T 0.0089 0.0025 0.0279 0.0185
16 16 16 16 var52 0.77181 0.84369 0.58958 0.64506 anti-vimentin 0.0005 <.0001 0.0162 0.0070
16 16 16 16 var53 0.68533 0.75791 0.52193 0.50456 a-tropomyosin 0.0034 0.0007 0.0381 0.0462
16 16 16 16 var54 0.01617 -0.02660 -0.01937 0.08509 anti-HSA 0.9526 0.9221 0.9432 0.7540
16 16 16 16 var55 0.57327 0.67219 0.28581 0.51984
Troponin I cardiac 0.0203 0.0043 0.2832 0.0390
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var69 var70 var71 var72 var45 0.61706 0.09202 0.12469 0.17306 anti-Annexin V 0.0109 0.7346 0.6454 0.5215
16 16 16 16 var46 -0.08724 0.18374 0.19963 0.25847 anti-Lipid A 0.7480 0.4958 0.4585 0.3337
16 16 16 16 var47 -0.01994 0.59535 0.67700 0.74752 anti-isopeptide bond 0.9416 0.0150 0.0040 0.0009
16 16 16 16 var48 0.20353 0.81952 0.85037 0.67561 anti-vitronectin 0.4496 0.0001 <.0001 0.0041
16 16 16 16 var49 0.10389 0.92782 0.94463 0.73885 anti-thrombin 0.7018 <.0001 <-0001 0.0011
16 16 16 16 var50 0.00506 0.58111 0.56372 0.80211 anti-osteocalcin 0.9852 0.0182 0.0230 0.0002
16 16 16 16 var51 0.09538 0.54414 0.50852 0.83541 anti-Troponin T 0.7253 0.0293 0.0443 <.0001
16 16 16 IS var52 0.00870 0.65303 0.64939 0.88081 anti-vimentin 0.9745 0.0061 0.0065 <.0001
16 16 16 16 var53 0.01548 0.47787 0.47727 0.75281 a-tropomyosin 0.9546 0.0612 0.0616 0.0008
16 16 16 16 var54 0.07009 0.30717 0.18028 0.35546 anti-HSA 0.7965 0.2472 0.5040 0.1767
16 16 16 16 var5S 0.05479 0.65955 0.69882 0.75765
Troponin I cardiac 0.8403 0.0054 0.0026 0.0007
16 IS 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var74 var75 var76 var77 var45 0.01481 0.01809 0.02818 0.16908 anti-Annexin V 0.9566 0.9470 0.9175 0.5313
16 16 16 16 var46 0.2S942 0.26907 0.27840 0.38657 anti-Lipid A 0.3129 0.3136 0.2964 0.1391
16 16 16 16 var47 0.58474 0.65180 0.62342 0.41490 anti-isopeptide bond 0.0174 0.0062 0.0099 0.1100
16 16 16 16 var48 0.942S2 0.88988 0.89675 0.70586 anti-vitronectin <.0001 <.0001 <.O001 0.0022
16 16 16 16 var49 0.9S775 0.93214 0.93101 0.77642 anti-thrombin <.0001 <.0001 <.0001 0.0004
16 16 16 16 var50 0.49822 0.75929 0.74504 0.47244 anti-osteocalcin 0.0495 0.0006 0.0009 0.0646
16 IS 16 16 var51 0.42540 0.55778 0.56584 0.50537 anti-Troponin T 0.1004 0.0248 0.0223 0.0458
16 16 16 16 var52 0.52156 0.62885 0.62684 0.53718 anti-vimentin 0.0383 0.0091 0.0094 0.0319
16 16 16 16 var53 0.34116 0.41420 0.41974 0.45260 a-tropomyosin 0.1960 0.1107 0.1055 0.0783
16 16 16 16 var54 0.30294 0.51025 0.50961 0.36926 anti-HSA 0.2541 0.0434 0.0438 0.1593
16 16 16 16 var55 0.69171 0.83699 0.82510 0.50350 Troponin I cardiac 0.0030 <.0001 <.0001 0.0468 16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var78 var79 var80 varδl var45 0.15344 -0.00012 0.02275 0.00114 anti-Annexin V 0.5705 0.9996 0.9334 0.9970
16 16 16 13 var46 0.50589 0.26566 0.26363 0.20119 anti-Lipid A 0.0456 0.3200 0.3239 0.5098
16 16 16 13 var47 0.49555 0.59261 0.66792 0.38017 anti-isopeptide bond 0.0509 0.0156 0.0047 0.2001
16 16 16 13 var48 0.26571 0.97884 0.93991 0.07649 anti-vitronectin 0.3199 <.0001 <.0001 0.8039
16 16 16 13 var49 0.34132 0.89570 0.9S959 0.18516 anti-thrombin 0.1957 <.0001 <.0001 0.5448
16 16 16 13 var50 0.59779 0.38623 0.59303 0.36874 anti-osteocalcin 0.0145 0.1395 0.0155 0.2150
16 16 16 13 var51 0.90986 0.31123 0.49975 0.80630 anti-Troponin T <.0001 0.2406 0.0487 0.0009
16 16 16 13 var52 0.86032 0.44672 0.60360 0.78560 anti-vimentin <-0001 0.0828 0.0133 0.0015
16 16 16 13 var53 0.94832 0.25123 0.41006 0.79761 a-tropomyosin <.0001 0.3480 0.1147 0.0011
16 16 16 13 var54 0.29946 0.27107 0.34418 0.27684 anti-HSA 0.2598 0.3099 0.1918 0.3598
16 16 16 13 var5S 0.38861 0.75701 0.76376 0.19666
Troponin I cardiac 0.1369 0.0007 0.0006 0.5196
16 16 16 13
Pearson Correlation Coefficients Prob > I rI under HO : Rho=0 Number of Observations var82 var83 var84 var85 var45 0.35636 0.12338 0.14713 0.00784 anti-Annexin V 0.2320 0.6880 0.6315 0.9797
13 13 13 13 var46 0.14974 0.19926 0.11299 0.26233 anti-Lipid A 0.6254 0.5140 0.7132 0.3866
13 13 13 13 var47 0.73157 0.73000 0.55574 0.58086 anti-isopeptide bond 0.0045 0.0046 0.0486 0.0374
13 13 13 13 var48 0.87007 0.73518 0.45914 0.90005 anti-vitronectin 0.0001 0.0042 0.1145 <.0001
13 13 13 13 var49 0.83489 0.87109 0.67201 0.96497 anti-thrombin 0.0004 0.0001 0.0119 <.0001
13 13 13 13 var50 0.45841 0.92359 0.99926 0.76211 anti-osteocalcin 0.1152 <.0001 <.0001 0.0025
13 13 13 13 varSl 0.39339 0.72892 0.71723 0.56361 anti-Troponin T 0.1836 0.0047 0.0058 0.0449
13 13 13 13 var52 0.60780 0.81278 0.73689 0.61991 anti-vimentin 0.0276 0.0007 0.0041 0.0238
13 13 13 13 var53 0.45228 0.61157 0.56042 0.40991 a-tropomyosin 0.1207 0.0263 0.0464 0.1642
13 13 13 13 var54 0.00322 0.49093 0.58324 0.55211 anti-HSA 0.9917 0.0885 0.0364 0.0504
13 13 13 13 varSS 0.76988 0.90512 0.72051 0.87658
Troponin I cardiac 0.0021 <.0001 0.0055 <.0001
13 13 13 13
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var86 var87 var88 var89 var45 0.16030 0.13726 -0.03433 0.29108 anti-Annexin V 0.5531 0.6257 0.9033 0.2925
16 15 15 15 var46 0.13209 0.03988 -0.04472 0.11229 anti-Lipid A 0.6258 0.8878 0.8743 0.6903
16 15 15 15 var47 0.46762 0.51893 0.14043 0.68753 anti-isopeptide bond 0.0678 0.0475 0.6177 0.0046
16 15 15 15 var48 0.84744 0.83109 0.05417 0.38535 anti-vitronectin ■c.OOOl 0.0001 0.8479 0.1561
16 15 15 15 var49 0.93391 0.82339 0.04889 0.51636 anti-thrombin <.0001 0.0002 0.8626 0.0488
16 15 15 15 varSO 0.42658 0.55534 0.17754 0.93840 anti-osteocalcin 0.0994 0.0316 0.5267 <.0001
IS 15 15 15 var51 0.21207 0.33082 0.45285 0.82998 anti-Troponin T 0.4304 0.2284 0.0901 0.0001
16 15 15 15 var52 0.34963 0.47719 0.49315 0.89537 anti-vimentin 0.1844 0.0721 0.0618 <.0001
16 15 15 15 var53 0.17138 0.26804 0.41280 0.77965 a-tropomyosin 0.5257 0.3341 0.1262 0.0006
16 15 15 15 var54 0.15341 0.22091 0.54954 0.32346 anti-HSA 0.5706 0.4288 0.0338 0.2396
16 15 15 15 var55 0.53294 0 74251 0.06021 0.70362
Troponin I cardiac 0.0335 0 .0015 0.8312 0.0034
16 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var90 var91 var92 var93 var45 0.30716 0.31161 0.24657 0.36594 anti-Annexin V 0.2654 0.2582 0.3573 0.1633
15 15 16 16 var46 0.38427 0.24404 0.13869 0.146S0 anti-Lipid A 0.1573 0.3807 0.6085 0.5880
15 15 16 16 var47 0.62082 0.75377 0.61455 0.72193 anti-isopeptide bond 0.0135 0.0012 0.0113 0.0016
15 15 16 16 var48 0.18671 0.51452 0.47584 0.27292 anti-vitronectin 0.5052 0.0497 0.0625 0.3065
15 15 16 16 var49 0.27383 0.66294 0.60380 0.38026 anti-thrombin 0.3234 0.0071 0.0133 0.1463
15 15 16 16 var50 0.63228 0.79051 0.96543 0.70399 anti-osteocalcin 0.0114 0.0005 <.0001 0.0023
15 15 16 16 var51 0.83371 0.80112 0.81250 0.84266 anti-Troponin T 0.0001 0.0003 0.0001 <.0001
15 15 16 16 var52 0.84705 0.89373 0.86154 0.93617 anti-vimentin <.0001 <.0001 <.0001 <.0001
15 15 16 16 var53 0.93877 0.82827 0.70344 0.92101 a-tropomyosin <.0001 0.0001 0.0024 ■c.OOOl
15 15 16 16 var54 -0.09653 0.12604 0.54381 0.00237 anti-HSA 0.7319 0.6544 0.0294 0.9931
15 15 16 16 var55 0.4S724 0.62452 0.71998 0.53740
Troponin I cardiac 0.0791 0.0128 0.0017 0.0318
15 15 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
Capture varl var2 var3 var56 0.69446 0.75106 0.79709 0.77993 anti-Apo Al 0.0028 0.0008 0.0002 0.0004
IS 16 16 16 var57 0.80940 0.81508 0.61271 0.50427
MHC class I 0.0001 0.0001 0.0116 0.0464
16 16 16 16 var58 0.87903 0.84176 0.58190 0.50814
Amyloid P protein <.0001 <.0001 0.0180 0.0445
16 16 16 16 var59 0.81297 0.85281 0.80618 0.72366 anti-sCD40 L 0.0001 <.0001 0.0002 0.0015 16 IS lβ 16 var60 0.70252 0.7097B 0.63399 0.61426 anti-kal1ikrein 0.0024 0.0021 0.0084 0.0114
16 16 16 16 varSl 0.66731 0.74929 0.89920 0.84440 Anti-Prothr Fl 0.0047 0.0008 <.0001 <.0001
16 16 16 16 var62 0.74555 0.82864 0.78790 0.69336 goat-ATIII 0.0009 <.0001 0.0003 0.0029
16 16 16 16 var63 0.78627 0.90029 0.95060 0.90188 anti-Throπibin 0.0003 ■=.0001 <.0001 <.0001
16 16 16 16 var64 0.52532 0.66836 0.97252 0.98407 anti-Factor VIII 0.0367 0.0047 <.0001 <.0001
16 16 16 16 var65 0.75676 0.80573 0.84106 0.78745 anti-heparan Sulph 0.0007 0.0002 <.0001 0.0003
16 16 16 16 var66 0.71633 0.84745 0.91876 0.84891 anti-Factor XI 0.0018 <.0001 <.0001 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var4 var5 var6 var7 var56 0.78983 0.38871 0.48720 0.29890 anti-Apo Al 0.0003 0.1368 0.0556 0.2608
16 16 16 16 var57 0.55305 0.57313 0.86634 0.15782 MHC class 0.0263 0.0203 <.0001 0.5594
16 16 16 16 var58 0.53091 0.76733 0.86073 0.40620
Amyloid P protein 0.0343 0.0005 <.0001 0.1185
16 16 16 16 var59 0.75251 0.58350 0.76827 0.31165 anti-sCD40 L 0.0008 0.0177 0.0005 0.2400
16 16 16 16 var60 0.62090 0.41865 0.43998 0.21638 anti-kallikrein 0.0103 0.1065 0.0881 0.4209
16 16 16 16 var61 0.86675 0.39770 0.63590 0.41933 Anti-Prothr Fl <.0001 0.1271 0.0081 0.1059
16 16 16 16 var62 0.73329 0.53435 0.80429 0.33497 goat-ATIII 0.0012 0.0330 0.0002 0.2047
16 16 16 16 var63 0.92769 0.51241 0.80973 0.38471 anti-Thrombin <.0001 0.0424 0.0001 0.1412
16 16 16 16 var64 0.98742 0.22030 0.50244 0.39449 anti-Factor VIII <.0001 0.4123 0.0473 0.1305
16 16 16 16 var65 0.81763 0.39117 0.75314 0.33425 anti-heparan Sulph 0.0001 0.1341 0.0008 0.2058
16 16 16 16 var66 0.88468 0.47963 0.77155 0.38685 anti-Factor XI <.0001 0.0601 0.0005 0.1388
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var8 var9 varlO varll var56 0.47836 0.87310 0.79596 0.44546 anti-Apo Al 0.0609 <.0001 0.0002 0.0838
16 16 16 16 var57 0.57779 0.54194 0.53467 0.62708
MHC class I 0.0191 0.0301 0.0329 0.0093
16 16 16 16 var58 0.77801 0.51938 0.51875 0.61759
Amyloid P protein 0.0004 0.0392 0.0395 0.0108
16 16 16 16 var59 0.67238 0.75615 0.74441 0.67062 anti-sCD40 L 0.0043 0.0007 0.0009 0.0045
16 16 16 16 var60 0.42431 0.72579 0.62790 0.55119 anti-kallikrein 0.1014 0.0015 0.0092 0.0269
16 16 16 16 var61 0.63326 0.86002 0.86704 0.38848 Anti-Prothr Fl 0.0085 <.0001 <.0001 0.1370
16 16 16 16 var62 0.65936 0.71780 0.72304 0.55262 goat-ATIII 0.0055 0.0017 0.0016 0.0264
16 16 16 16 var63 0.68114 0.92693 0.91901 0.41270 anti-Thrombin 0.0037 <.0001 <.0001 0.1121
16 16 16 16 var64 0.50997 0.98805 0.98909 0.07530 anti-Factor VIII 0.0436 <.0001 <.0001 0.7817
16 16 16 16 var65 0.60958 0.82108 0.81349 0.32148 anti-heparan Sulph 0.0122 <.0001 0.0001 0.2247
16 16 16 16 var66 0.65038 0.87679 0.87627 0.41788 anti-Factor XI 0.0064 ς.0001 <.0001 0.1073
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : RhO=O Number of Observations varl2 varl3 varl4 varl5 var56 0.83955 0.84071 0.05527 0.21003 anti-Apo Al <-0001 <.0001 0.8389 0.4349
16 16 16 16 var57 0.52562 0.76332 0.06398 0.34104
MHC class I 0.0365 0.0006 0.8139 0.1961
16 16 16 16 var58 0.48868 0.77498 0.32614 0.56383 Amyloid P protein 0.0548 0.0004 0.2177 0.0229
16 16 16 16 var59 0.73594 0.85378 0.17704 0.40781 anti-sCD40 L 0.0012 <.0001 0.5119 0.1169
16 16 16 16 varδO 0.67821 0.75491 0.02053 0.16203 anti-kallikrein 0.0039 0.0007 0.9399 0.5488
16 16 16 16 varSl 0.85565 0.82565 0.23724 0.40091 Anti-Prothr Fl ■=.0001 <.0001 0.3763 0.1238
16 16 16 16 var62 0.70974 0.82780 0.20422 0.41789 goat-ATIII 0.0021 <.0001 0.4481 0.1072
16 16 16 16 varS3 0.91899 0.9S728 0.14700 0.37340 anti-Thrombin <.0001 <.0001 0.5870 0.1543
16 16 16 16 var64 0.99501 0.83476 0.10338 0.24730 anti-Factor VIII <.0001 <.0001 0.7032 0.3558
16 16 16 16 var65 0.81185 0.86723 0.13009 0.28841 anti-heparan Sulph 0.0001 •=.0001 0.6311 0.2787
16 16 16 16 var66 0.87477 0.90574 0.17852 0.39021 anti-Factor XI <.0001 <-0001 0.5083 0.1351
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations varlβ varl7 varlδ var!9 var56 0.74659 0.88291 0.82448 0.74048 anti-Apo Al 0.0009 <.0001 <.0001 0.0010
16 16 16 16 var57 0.45311 0.57520 0.58563 0.52259
MHC class I 0.0780 0.0197 0.0171 0.0378
16 16 16 16 var58 0.47465 0.59516 0.57377 0.44263
Amyloid P protein 0.0632 0.0150 0.0201 0.0860
16 16 16 16 var59 0.66951 0.80243 0.78448 0.73373 anti-sCD40 L 0.0046 0.0002 0.0003 0.0012
16 16 16 16 var60 0.59197 0.75149 0.67462 0.55135 anti-kallikrein 0.0157 0.0008 0.0041 0.0268
16 16 16 16 var61 0.78682 0.87694 0.85881 0.89284 Anti-Prothr Fl 0.0003 <.0001 <.0001 .= .0001
16 16 16 16 var62 0.64443 0.75035 0.74488 0.74650 goat-ATIII 0.0070 0.0008 0.0009 0.0009
16 16 16 16 var63 0.83962 0.93913 0.94442 0.88991 anti-Thrombin <.0001 ■=.0001 <.0001 <.0001
16 16 16 16 var64 0.93208 0.96279 0.97633 0.96930 anti-Factor VIII <.0001 <.0001 <.0001 <.0001 16 16 16 IS var65 0.72328 0.82242 0.81097 0. 81231 anti-heparan Sulph 0.0015 •=.0001 0.0001 0 .0001
16 16 16 16 varS6 0.78802 0.88724 0.88911 0. 88985 anti-Factor XI 0.0003 <.0001 <.0001 < .0001
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : RhO=O Number of Observations var20 var21 var22 var23 var56 0.67681 0.49753 0.22494 0.38417 anti-Apo Al 0.0040 0.0499 0.4023 0.1418
16 16 16 16 var57 0.41117 0.93372 0.29462 0.37058
MHC class I 0.1136 <.0001 0.2680 0.1577
16 16 16 16 var58 0.40976 0.84607 0.21692 0.60158
Amyloid P protein 0.1150 <.0001 0.4197 0.0137
16 16 16 16 var59 0.61897 0.84044 0.40463 0.50236 anti-sCD40 L 0.0106 <.0001 0.1200 0.0474
16 16 16 16 var60 0.50703 0.43133 0.14342 0.33199 anti-kallikrein 0.0450 0.0953 0.5962 0.2090
16 16 16 16 varδl 0.74284 0.70785 0.40634 0.53714 Anti-Prothr Fl 0.0010 0.0022 0.1183 0.0319
16 16 16 16 var62 0.59106 0.87662 0.40248 0.47376 goat-ATIII 0.0159 <.0001 0.1222 0.0638
IS 16 16 16 var63 0.82516 0.85304 0.38460 0.47851 anti-Throitibin <.0001 <.0001 0.1413 0.0608
16 IS 16 16 var64 0.94536 0.54132 0.33089 0.39220 anti-Factor VIII <.0001 0.0303 0.2106 0.1330
16 16 16 16 var65 0.69255 0.80335 0.28951 0.47575 anti-heparan Sulph 0.0029 0.0002 0.2768 0.0625
16 16 16 16 var66 0.75683 0.83926 0.40822 0.47283 anti-Factor XI 0.0007 <.0001 0.1165 0.0644
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var24 var25 var26 var27 var56 0.67551 0.78264 0.79702 0.79080 anti-Apo Al 0.0041 0.0003 0.0002 0.0003
16 16 16 16 var57 0.48215 0.55904 0.63228 0.53890
MHC class I 0.0586 0.0244 0.0086 0.0312
16 16 16 16 var58 0.44511 0.56862 0.62135 0.53531
Amyloid P protein 0.0840 0.0215 0.0102 0.0326
16 16 16 16 var59 0.67769 0.77415 0.83905 0.73388 anti-sCD40 L 0.0039 0.0004 <.0001 0.0012
16 16 16 16 varβO 0.51345 0.62279 0.64657 0.62478 anti-kal1ikrein 0.0419 0.0100 0.0068 0.0097
16 16 16 16 varSl 0.77604 0.87119 0.90743 0.84650 Anti-Prothr Fl 0.0004 <.0001 <.0001 ■=.0001
16 16 16 16 var62 0.65030 0.74619 0.81597 0.71363 goat-ATIII 0.0064 0.0009 0.0001 0.0019
16 16 16 16 var63 0.81767 0.92749 0.95255 0.92365 anti-Thrombin 0.0001 <.0001 <.0001 <.0001
IS 16 16 16 var64 0.87107 0.96934 0.94312 0.98718 anti-Factor VIII <.0001 <.0001 <.0001 < .0001
16 16 16 16 var65 0.69820 0.805S3 0.82757 0.80614 anti-heparan Sulph 0.0026 0.0002 <-0001 0.0002
16 16 16 16 var66 0.78845 0.88287 0.92672 0.87102 anti-Factor XI 0.0003 <.0001 <.0001 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var28 var29 var30 var31 var56 0.21602 0.59164 0.29522 0.27810 anti-Apo Al 0.4217 0.0158 0.2670 0.2970
16 16 16 16 var57 0.62645 0.24026 0.25531 0.30454
MHC class I 0.0094 0.3701 0.3399 0.2515
16 16 16 16 var58 0.66042 0.47712 0.52320 0.58180
Amyloid P protein 0.0054 0.0617 0.0376 0.0181
16 16 16 16 var59 0.61188 0.32020 0.37758 0.40682 anti-sCD40 L 0.0118 0.2266 0.1494 0.1179
16 16 16 16 var60 0.27318 0.76254 0.24385 0.25247 anti-kallikrein 0.3060 0.0006 0.3628 0.3455
16 16 16 16 var61 0.38825 0.09001 0.42825 0.40472 Anti-Prothr Fl 0.1373 0.7403 0.0979 0.1200
16 16 16 16 var62 0.56782 0.14421 0.38008 0.38601 goat-ATIII 0.0218 0.5942 0.1465 0.1397
16 16 16 16 var63 0.36179 0.22794 0.39461 0.38756 anti-Thrombin 0.1685 0.3959 0.1304 0.1380
16 16 16 16 var64 0.00400 0.03748 0.32971 0.27582 ant x- Fact or VIII 0.9883 0.8904 0.2124 0.3011
IS 16 16 16 var65 0.32674 0.13972 0.37485 0.37037 anti-heparan Sulph 0.2168 0.6058 0.1526 0.1579
16 16 16 16 varS6 0.40956 0.12485 0.38881 0.36939 anti-Factor XI 0.1152 0.6450 0.1367 0.1591
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var32 var33 var34 var35 var56 -0.14091 0.90785 0.71342 0.46757 anti-Apo Al 0.6027 <.0001 0.0019 0.0678
16 16 16 16 var57 0.19535 0.53527 0.63251 0.14443
MHC class I 0.4684 0.0326 0.0086 0.5936
16 16 16 16 var58 0.06370 0.55006 0.46316 0.00484
Amyloid P protein 0.8147 0.0273 0.0708 0.9858
16 16 16 16 var59 0.17611 0.76222 0.85748 0.33119 anti-sCD40 L 0.5141 0.0006 ■=.0001 0.2102
16 16 16 16 var60 -0.12495 0.78201 0.53727 0.32035 anti-kailikrein 0.6447 0.0003 0.0319 0.2264
16 16 16 16 var61 0.08377 0.83940 0.96884 0.50614 Anti-Prothr Fl 0.7577 <.0001 <.0001 0.0455
16 16 16 16 var62 0.17657 0.69824 0.85277 0.32331 goat-ATIII 0.5130 0.0026 <.0001 0.2219
16 16 16 16 var63 -0.01028 0.92123 0.90374 0.47699 anti-Thrombin 0.9698 <.0001 <.0001 0.0617
16 16 16 16 var64 -0.17696 0.97208 0.92853 0.66418 anti-Factor VIII 0.5121 <.0001 <.0001 0.0050
16 IS 16 16 var65 0.05781 0.80125 0.84070 0.39887 anti-heparan Sulph 0.8316 0.0002 <.0001 0.1259
16 16 16 16 var66 0.07932 0.85449 0.93263 0.48178 anti-Factor XI 0.7703 <.0001 <.0001 0.0588
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var36 var37 var38 var39 var56 0.75117 0.83431 0.30705 0.86289 anti-Apo Al 0.0008 <.0001 0.2474 <.0001
16 16 16 16 var57 0.51398 0.58502 0.67649 0.50527
MHC class I 0.0417 0.0173 0.0040 0.0459
16 16 16 16 var58 0.43449 0.59883 0.52808 0.49004
Amyloid P protein 0.0926 0.0142 0.0355 0.0540
16 16 16 16 var59 0.73186 0.81129 0.50116 0.73235 anti-sCD40 L 0.0013 0.0001 0.0480 0.0013
16 16 16 16 var60 0.56303 0.70232 0.22336 0.71110 anti-kallikrein 0.0232 0.0024 0.4057 0.0020
16 16 16 16 varSl 0.88936 0.86365 0.35988 0.85172 Anti-Prothr Fl <.0001 <.0001 0.1710 <.0001
16 16 16 16 var62 0.74073 0.75267 0.54910 0.69290 goat-ATIII 0.0010 0.0008 0.0276 0.0029
16 16 16 16 var63 0.89294 0.93591 0.63356 0.90927 ant i - Thr oπib in <.0001 <.0001 0.0084 <.0001
16 16 16 16 var64 0.97863 0.95190 0.41726 0.99274 anti-Factor VIII <.0001 <.0001 0.1078 <-0001
16 16 16 16 var65 0.80627 0.79624 0.45336 0.80551 anti-heparan Sulph 0.0002 0.0002 0.0778 0.0002
16 16 16 16 var6S 0.88826 0.87719 0.60729 0.85819 anti-Factor XI <.0001 <.0001 0.0126 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var40 var41 var42 var43 var56 0.83307 0.73718 0.79380 0.71406 anti-Apo Al <.0001 0.0011 0.0002 0.0019
16 16 16 16 var57 0.66543 0.81656 0.38580 0.41863
MHC class I 0.0049 0.0001 0.1400 0.1066
16 16 16 16 var58 0.67605 0.80244 0.34488 0.33310
Amyloid P protein 0.0040 0.0002 0.1908 0.2074
16 16 16 16 var59 0.72507 0.85369 0.62033 0.62800 anti-sCD40 L 0.0015 <.0001 0.0104 0.0092
16 16 16 16 varδo 0.78878 0.64375 0.64691 0.52844 anti-kallikrein 0.0003 0.0071 0.0068 0.0353
16 16 16 16 var61 0.62276 0.80547 0.76154 0.79138 Anti-Prothr Fl 0.0100 0.0002 0.0006 0.0003
16 16 16 16 var62 0.66267 0.86123 0.60829 0.63190 goat-ATIII 0.0052 <.0001 0.0124 0.0086
16 16 16 16 var63 0.85403 0.96038 0.80195 0.82545 anti-Thrombin <.0001 <.0001 0.0002 <.0001
16 16 16 16 varS4 0.71503 0.78161 0.89754 0.94416 anti-Factor VIII 0.0018 0.0003 <.0001 <.0001
16 16 16 16 var65 0.67051 0.84864 0.67643 0.72399 anti-heparan Sulph 0.0045 <.0001 0.0040 0.0015
16 16 16 16 var66 0.77183 0.91304 0.77315 0.80300 anti-Factor XI 0.0005 <.0001 0.0004 0.0002
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var45 var46 var47 var48 var56 0.22451 0.12790 0.60112 0.42181 anti-Apo Al 0.4032 0.6369 0.0138 0.1037
16 16 16 16 var57 0.09029 0.19281 0.74525 0.82139
MHC class I 0.7395 0.4743 0.0009 <.0001
16 16 16 16 var58 -0.03494 0.47730 0.52047 0.77267
Amyloid P protein 0.8978 0.0615 0.0387 0.0005
16 16 16 16 var59 0.14438 0.24193 0.76952 0.67235 anti-sCD40 L 0.5937 0.3667 0.0005 0.0043
16 16 16 16 var60 0.14086 0.12904 0.47664 0.44203 anti-kallikrein 0.6028 0.6339 0.0620 0.0865
16 16 16 16 var61 0.26632 0.22113 0.72819 0.43197 Anti-Prothr Fl 0.3188 0.4105 0.0014 0.0947
16 16 16 16 var62 0.13746 0.25363 0.75958 0.67371 goat-ATIII 0.6117 0.3432 0.0006 0.0042
16 16 16 16 var63 0.25776 0.21299 0.83471 0.65991 anti-Thrombin 0.3351 0.4284 <.0001 0.0054
16 16 16 16 var64 0.35195 0.09194 0.72862 0.28297 anti-Factor VIII 0.1813 0.7349 0.0014 0.2883
16 16 16 16 var65 0.40772 0.19440 0.72196 0.59588 anti-heparan Sulph 0.1170 0.4706 0.0016 0.0149
16 16 16 16 var66 0.23719 0.20832 0.83543 0.61899 anti-Factor XI 0.3764 0.4388 <.0001 0.0106
16 15 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var49 var50 var51 var52 var56 0 .54438 0 .99383 0 .76602 0 .80044 anti-Apo Al 0.0292 <.0001 0.0005 0.0002
16 16 16 16 var57 0 .90037 0 .41239 0 .37751 0 .55998 MHC class I <.0001 0.1124 0.1494 0.0241
16 16 16 16 var58 0.85767 0.54216 0.55753 0.57185
Amyloid P protein <.0001 0.0300 0.0248 0.0206
16 16 16 16 var59 0.77875 0.67755 0.62568 0.74075 anti-sCD40 L 0.0004 0.0039 0.0095 0.0010
16 16 16 16 varSO 0.55361 0.98509 0.65645 0.65942 anti-kallikrein 0.0261 <.0001 0.0057 0.0055
16 16 16 16 varβl 0.58615 0.66931 0.70345 0.79713 Anti-Prothr Fl 0.0170 0.0046 0.0024 0.0002
16 16 16 16 var62 0.76213 0.53327 0.56034 0.69132 goat-ATIII O.O006 0.0334 0.0240 0.0030
16 16 16 16 varS3 0.74300 0.74455 0.78936 0.92184 anti-Thrombin O.OOIO 0.0009 0.0003 <.0001
16 16 16 16 var64 0.39656 0.75026 0.85461 0.95719 anti-Factor VIII 0.1283 0.0008 <.0001 <.0001
16 16 16 16 var65 0.73715 0.64325 0.63022 0.77181 anti-heparan Sulph 0.0011 0.0072 0.0089 0.0005
16 16 16 16 varS6 0.70252 0.65150 0.69992 0.84369 anti-Factor XI 0.0024 0.0063 0.0025 •=.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var53 var54 var55 var56 var56 0.64886 0.50657 0.73409 1.00000 anti-Apo Al 0.0065 0.0452 0.0012
16 16 16 16 var57 0.38928 -0.00485 0.65616 0.41510
MHC class I 0.1361 0.9858 0.0058 0.1099
16 16 16 16 var58 0.47978 0.34553 0.65347 0.52135
Amyloid P protein 0.0600 0.1899 0.0060 0.0384
16 16 16 16 var59 0.61047 0.17747 0.65002 0.67330 anti-sCD40 L 0.0120 0.5108 0.0064 0.0043
16 16 16 16 var60 0.47741 0.66249 0.71871 0.96717 anti-kallikrein 0.0615 0.0052 0.0017 <.0001
16 16 16 16 var61 0.75866 0.00430 0.49752 0.69367 Anti-Prothr Fl 0.0007 0.9874 0.0499 0.0029
16 16 16 16 var62 0.60527 -0.04395 0.58590 0.54758 goat-ATIII 0.0130 0.8716 0.0171 0.0281
16 16 16 16 var63 0.80495 0.13738 0.75189 0.77718 anti-Thrombin 0.0002 0.6119 0.0008 0.0004 16 16 16 IS var64 0.90426 0.09S19 0.56752 0.80673 anti-Factor VIII <.0001 0.7230 0.0219 0.0002
16 16 16 16 var65 0.68533 0.01617 0.57327 0.67354 anti-heparan Sulph 0.0034 0.9526 0.0203 0.0042
16 16 16 IS var66 0.75791 -0.02660 0.67219 0.68702 anti-Factor XI 0.0007 0.9221 0.0043 0.0033
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var57 var58 var59 var60 var56 0.41510 0.52135 0.67330 0.96717 anti-Apo Al 0.1099 0.0384 0.0043 <.0001
16 16 16 16 var57 1.00000 0.81416 0.84170 0.34311 MHC class 0.0001 <.0001 0.1932
16 16 lβ 16 var58 0.81416 1.00000 0.68754 0.51769
Amyloid P protein 0.0001 0.0032 0.0400
16 16 16 16 var59 0.84170 0.68754 1.00000 0.58632 anti-sCD40 L <.0001 0.0032 0.0170
16 16 16 16 var60 0.34311 0.51769 0.58632 1.00000 anti-kallikrein 0.1932 0.0400 0.0170
16 16 16 16 var61 0.69993 0.52850 0.93308 0.54622 Anti-Prothr Fl 0.0025 0.0353 <.0001 0.0286
16 16 16 16 var62 0.8S798 0.64905 0.95836 0.42345 goat-ATIII <.0001 0.0065 <.0001 0.1022
16 16 16 16 var63 0.79845 0.72849 0.87892 0.64372 anti-Thrombin 0.0002 0.0014 <.0001 0.0071
16 16 16 IS var64 0.47672 0.42968 0.69157 0.63566 anti-Factor VIII 0.0619 0.0967 0.0030 0.0081
16 16 IS 16 var65 0.80566 0.69091 0.80340 0.55196 anti-heparan Sulph 0.0002 0.0030 0.0002 0.0266
16 16 16 16 var66 0.80840 0.63199 0.92093 0.53321 anti-Factor XI 0.0002 0.0086 <.0001 0.0334
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : RhO=O Number of Observations var61 var62 var63 var64 var56 0.69367 0.54758 0.77718 0.80673 anti-Apo Al 0.0029 0.0281 0.0004 0.0002
16 16 16 16 var57 0.69993 0.86798 0.79845 0.47672 MHC class 0.0025 <.0001 0.0002 0.0619
16 16 16 16 var58 0.52850 0.64905 0.72849 0.42968
Amyloid P protein 0.0353 0.0065 0.0014 0.0967
16 16 16 16 var59 0.93308 0.95836 0.87892 0.69157 anti-sCD40 L <.0001 <.0001 <.0001 0.0030
16 16 16 16 varSO 0.54622 0.42345 0.64372 0.63566 anti-kallikrein 0.0286 0.1022 0.0071 0.0081
16 16 16 16 varδl 1.00000 0.92034 0.88109 0.83254 Anti-Prothr Pl ■=.0001 <.0001 <.0001
IS 16 16 16 var62 0.92034 1.00000 0.87693 0.67017 goat-ATIII <.0001 <.0001 0.0045
16 16 16 16 var63 0.88109 0.87693 1.00000 0.89101 anti-Thrombin <.0001 <.0001 <.0001
16 16 16 16 var64 0.83254 0.67017 0.89101 1.00000 anti-Factor VIII <.0001 0.0045 <.0001
16 16 16 16 var65 0.83324 0.79258 0.89485 0.78724 anti-heparan Sulph <.0001 0.0003 <-0001 0.0003
16 16 16 16 var66 0.94053 0.95546 0.96495 0.84577 anti-Factor XI <.0001 <.0001 <.0001 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var65 var66 var67 var68 var56 0.67354 0.68702 0.45138 0.60675 anti-Apo Al 0.0042 0.0033 0.0793 0.0127
16 16 16 16 var57 0.80566 0.80840 0.42942 0.55575
MHC class I 0.0002 0.0002 0.0969 0.0254
16 16 16 16 var58 0.69091 0.63199 0.46419 0.49802
Amyloid P protein 0.0030 0.0086 0.0701 0.0496
16 16 16 16 var59 0.80340 0.92093 0.32669 0.63146 anti-sCD40 Ii 0.0002 <.0001 0.2168 0.0087
16 16 16 16 var60 0.55196 0.53321 0.33378 0.50861 anti-kallikrein 0.0266 0.0334 0.2064 0.0442
16 16 16 16 var61 0.83324 0.94053 0.43060 0.65134 Anti-Prothr Fl <.0001 <.0001 0.0959 0.0063
16 16 16 16 var62 0.79258 0.95546 0.31603 0.55917 goat-ATIII 0.0003 <.0001 0.2331 0.0243
16 16 16 16 var63 0.89485 0.96495 0.57403 0.67873 anti-Thrombin <.0001 <.0001 0.0201 0.0038
16 16 16 16 var64 0.78724 0.84577 0.62785 0.66180 anti-Factor VIII 0.0003 <-0001 0.0092 0.0052
16 16 16 16 var65 1.00000 0.85733 0.59657 0.59293 anti-heparan Sulph ■c.OOOl 0.0147 0.0155
16 16 16 16 var6S 0.85733 1.00000 0.46452 0.64405 anti-Factor XI <.0001 0.0699 0.0071
IS 16 16 16
Pearson Correlation Coefficients
Prob under HO : Rho=0
Number of Observations var69 var70 var71 var72 var56 0.00325 0.57872 0.57067 0.80475 anti-Apo Al 0.9905 0.0188 0.0210 0.0002
16 16 16 16 var57 0.02781 0.84444 0.90991 0.73000 MHC class 0.9186 <.0001 <.0001 0.0013
16 16 16 16 var58 -0.06297 0.89584 0.87850 0.76428
Amyloid P protein 0.8168 <.0001 <.0001 0.0006
16 16 16 16 var59 -0.05854 0.70912 0.74740 0.89142 anti-sCD40 L 0.8295 0.0021 0.0009 <.0001
16 16 16 16 var60 0.00376 0.54484 0.51836 0.72224 anti-kallikrein 0.9890 0.0291 0.0397 0.0016
16 16 16 16 var61 -0.02920 0.58184 0.62968 0.83652 Anti-Prothr Fl 0.9145 0.0181 0.0089 <.0001
16 ie 16 16 var62 -0.06574 0.71290 0.76943 0.82913 goat-ATIII 0.8089 0.0019 0.0005 <.0001
16 16 16 16 var63 0.02782 0.81662 0.84772 0.93618 anti-Thrombin 0.9185 0.0001 <.0001 <.0001
16 16 16 16 var64 0.03215 0.54616 0.56677 0.80233 anti-Factor VIII 0.9059 0.0286 0.0221 0.0002
16 16 16 16 var65 0.33185 0.76280 0.83777 0.77382 anti-heparan Sulph 0.2092 0.0006 <.0001 0.0004
16 16 16 16 var66 -0.02559 0.72691 0.78142 0.88560 anti-Factor XI 0.9251 0.0014 0.0004 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > I rI under HO : Rho=0 Number of Observations var74 var75 var76 var77 var56 0.47378 0.72972 0.71552 0.45613 anti-Apo Al 0.0638 0.0013 0.0018 0.0758
16 16 16 16 var57 0.88747 0.79198 0.78583 0.70117
MHC class I <.0001 0.0003 0.0003 0.0025
16 16 16 16 var58 0.89351 0.86957 0.87507 0.89094
Amyloid P protein < .0001 <.0001 <.0001 < .0001
16 16 16 16 var59 0.76310 0.79359 0.78309 0.53380 anti-sCD40 L 0.0006 0.0002 0.0003 0.0332
16 16 16 16 varβO 0.47301 0.75358 0.73853 0.45899 anti-kallikrein 0.0643 0.0007 0.0011 0.0737
16 16 16 16 varβl 0.55563 0.60228 0.59142 0.41005 Anti-Prothr Fl 0.0254 0.0136 0.0158 0.1147
IS 16 16 16 var62 0.76474 0.71996 0.71531 0.47354 goat-ATIII 0.0006 0.0017 0.0018 0.0639
16 16 16 16 var63 0.74494 0.78812 0.78625 0.63812 anti-Thrombin 0.0009 0.0003 0.0003 0.0078
16 16 16 16 varS4 0.37788 0.50088 0.49419 0.40403 anti-Factor VIII 0.1490 0.0481 0.0517 0.1206
16 16 16 16 var65 0.67201 0.68335 0.67505 0.74450 anti-heparan Sulph 0.0044 0.0035 0.0041 0.0009
16 16 16 16 var66 0.70205 0.71249 0.70754 0.49117 anti-Factor XI 0.0024 0.0020 0.0022 0.0534
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : RhO=O Number of Observations var78 var79 var80 var81 var56 0.61788 0.36530 0.57287 0.39541 anti-Apo Al 0.0107 0.1641 0.0204 0.1811
16 16 16 13 var57 0.39071 0.83187 0.88875 0.32083
MHC class I 0.1346 <.0001 <.0001 0.2852
16 16 16 13 var58 0.58729 0.83022 0.89423 0.41410
Amyloid P protein 0.0168 <.0001 <.0001 0.1595
16 16 16 13 var59 0.61025 0.63506 0.79736 0.54952 anti-sCD40 L 0.0121 0.0082 0.0002 0.0517
16 16 16 13 var60 0.49864 0.37741 0.56517 0.26307 anti-kallikrein 0.0493 0.1496 0.0225 0.3852
16 16 16 13 var61 0.69006 0.38815 0.60344 0.60123 Anti-Prothr Fl 0.0031 0.1374 0.0133 0.0297
16 16 16 13 var62 0.55469 0.64833 0.78111 0.49617 goat-ATIII 0.0257 0.0066 0.0004 0.0846
16 16 16 13 var63 0.74530 0.65661 0.80276 0.58786 anti-Thrombin 0.0009 0.0057 0.0002 0.0346
16 16 16 13 varS4 0.79500 0.27214 0.46783 0.68834 anti-Factor VIII 0.0002 0.3079 0.0676 0.0093
16 16 16 13 var65 0.62433 0.55984 0.72023 0.45312 anti-heparan Sulph 0.0097 0.0241 0.0017 0.1200
16 16 16 13 var66 0.66492 0.60025 0.74791 0.53304 anti-Factor XI 0.0049 0.0140 0.0009 0.0607
16 16 16 13
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var82 var83 var84 var85 var56 0.48432 0.92253 0.99179 0.73830 anti-Apo Al 0.0935 <.0001 <.0001 0.0040
13 13 13 13 var57 0.92573 0.81050 0.53060 0.81822
MHC class I <.0001 0.0008 0.0621 0.0006
13 13 13 13 var58 0.71118 0.83827 0.62366 0.91534
Amyloid P protein 0.0064 0.0003 0.0227 <.0001
13 13 13 13 var59 0.74624 0.94484 0.82593 0.80785 anti-sCD40 L 0.0034 <.0001 0.0005 0.0008
13 13 13 13 var60 0.40728 0.89769 0.99065 0.77195 anti-kallikrein 0.1672 <.0001 <.0001 0.0020
13 13 13 13 var61 0.58827 0.78438 0.75388 0.54583 Anti-Prothr Fl 0.0344 0.0015 0.0029 0.0537
13 13 13 13 var62 0.78204 0.82710 0.64553 0.72327 goat-ATIII 0.0016 0.0005 0.0172 0.0052
13 13 13 13 var63 0.77616 0.88286 0.74148 0.75261 anti-Thrombin 0.0018 <.0001 0.0037 0.0030
13 13 13 13 var64 0.54320 0.73909 0.72522 0.48394 anti-Factor VIII 0.0551 0.0039 0.0050 0.0938
13 13 13 13 var65 0.84130 0.79524 0.69809 0.64623 anti-heparan Sulph 0.0003 0.0012 0.0080 0.0170
13 13 13 13 var66 0.74952 0.81911 0.67479 0.66844 anti-Factor XI 0.0032 0.0006 0.0114 0.0125
13 13 13 13
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var86 var87 var88 var89 var56 0.41392 0.56501 0.16775 0.96775 anti-Apo Al 0.1110 0.0282 0.5501 < .0001
16 15 15 15 var57 0.81703 0.65221 0.00616 0.47210
MHC class I 0.0001 0.0084 0.9826 0.0756 ie 15 15 15 var58 0.74754 0.67305 0.18205 0.51410
Amyloid P protein 0.0009 0.0060 0.5161 0.0499
16 15 15 15 var59 0.60014 0.47145 0.12895 0.71475 anti-sCD40 L 0.0140 0.0761 0.6469 0.0027
16 15 15 15 varδO 0.42452 0.56156 0.14615 0.87270 anti-kallikrein 0.1012 0.0294 0.6032 <.0O01
IS 15 15 15 varSl 0.44975 0.34650 0.09980 0.78971 Anti-Prothr Fl 0.0805 0.2058 0.7234 0.0005
16 15 15 15 var62 0.62512 0.51250 0.02517 0.63146 goat-ATIII 0.0096 0.0508 0.9290 0.0116
16 15 IS 15 var63 0.61964 0.67057 0.22992 0.86846 anti-Thrombin 0.0105 0.0062 0.4097 <-0001
16 15 15 15 var64 0.29243 0.42358 0.31938 0.92509 anti-Factor VIII 0.2717 0.1156 0.2459 <.0001
16 15 15 15 var65 0.73620 0.61551 0.09691 0.77124 anti-heparan Sulph 0.0011 0.0146 0.7312 0.0008
16 15 15 15 var66 0.57573 0.57814 0.09622 0.79402 anti-Factor XI 0.0196 0.0240 0.7330 0.0004
16 15 15 15
Pearson Correlation Coefficients Prob > I rI under HO : RhO=O Number of Observations var90 var91 var92 var93 var56 0.69417 0.81900 0.97314 0.76502 anti-Apo Al 0.0041 0.0002 <.0001 0.0006
15 15 16 16 var57 0.40616 0.71517 0.47773 0.49011
MHC class I 0.1330 0.0027 0.0613 0.0539
15 15 16 16 var58 0.40490 0.65629 0.60988 0.42569
Amyloid P protein 0.1344 0.0079 0.0121 0.1002
15 15 16 16 var59 0.62380 0.88281 0.67717 0.69832 anti-sCD40 L 0.0130 <.0001 0.0040 0.0026
15 15 16 16 var60 0.50800 0.68568 0.93325 0.57932 anti-kallikrein 0.0532 0.0048 <.0001 0.0187
15 15 16 16 var61 0.80517 0.94055 0.68708 0.85432 Anti-Prothr Fl 0.0003 <.0001 0.0033 <.0001
15 15 16 16 varS2 0.64852 0.84910 0.55244 0.69887 goat-ATIII 0.0089 ■c.OOOl 0.0265 0.0026
15 15 16 16 var63 0.81434 0.95644 0.82220 0.89091 anti-Thrombin 0.0002 <.0001 <.0001 <.0001
15 15 16 16 var64 0.92181 0.90994 0.83509 0.99289 anti-Factor VIII <.0001 <.0001 <.0001 <.0001
15 15 16 16 var65 0.72665 0.93190 0.74705 0.79661 anti-heparan Sulph 0.0022 <.0001 0.0009 0.0002
15 15 16 16 var66 0.80575 0.93380 0.69840 0.86555 anti-Factor XI 0.0003 <.0001 0.0026 <.0001
15 15 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations
Capture varl var2 var3 var67 0.42853 0.41157 0.59364 0.61915 anti-c-jun 0.0977 0.1132 0.0153 0.0105
16 16 16 16 var68 0.53166 0.54156 0.68922 0.65043 anti-Fra-2 0.0340 0.0303 0.0031 0.0064
16 16 16 16 var69 0.02274 0.05661 -0.00684 0.00385 anti-Fra-1 0.9334 0.8350 0.9799 0.9887
16 16 16 16 var70 0.92490 0.93068 0.64023 0.58421 anti-Jun B <-0001 <.0001 0.0076 0.0175
16 16 16 16 var71 0.90084 0.92293 0.66398 0.58842 anti-P-c-Jun <.0001 ■=.0001 0.0050 0.0165
16 16 16 16 var72 0.83004 0.90725 0.89004 0.84504 anti-TGase3 <.0001 <.O001 <.0001 <.0001
16 16 16 16 var74 0.91067 0.91469 0.52639 0.43266 anti-PSA <.0001 <.0001 0.0362 0.0942
16 16 16 16 var75 0.93923 0.94447 0.61580 0.53344 anti-erbB2 <.0001 <.0001 0.0111 0.0333
16 16 16 16 var76 0.93867 0.94841 0.61244 0.53225 anti-VEGF <.0001 <.0001 0.0117 0.0338
16 16 16 16 var77 0.80153 0.74495 0.50938 0.47936 anti-alpha synuclein 0.0002 0.0009 0.0439 0.0603
16 16 16 16 var78 0.52692 0.62008 0.84333 0.88376 anti-mucin-1 0.0360 0.0104 <.0001 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var4 var5 varS var7 var67 0.61710 0.00427 0.37975 0.13357 anti-c-jun 0.0109 0.9875 0.1468 0.6219
IS 16 16 16 varS8 0.66543 0.25592 0.42827 0.13663 anti-Fra-2 0.0049 0.3387 0.0979 0.6139
IS 16 16 16 var69 0.00753 -0.11547 0.10750 -0.08661 anti-Fra-1 0.9779 0.6702 0.6919 0.7498
16 16 16 16 var70 0.60531 0.54221 0.95539 0.18542 anti-Jun B 0.0130 0.0300 <.0001 0.4918
16 16 16 16 var71 0.62415 0.55053 0.94711 0.19951 anti-P-c-Juti 0.0098 0.0271 <.0001 0.4588
16 16 16 16 var72 0.85751 0.63843 0.79704 0.39437 anti-TGase3 <.0001 0.0078 0.0002 0.1306
16 16 16 16 var74 0.46552 0.70436 0.96401 0.17992 anti-PSA 0.0692 0.0023 <.0001 0.5049
16 16 16 16 var75 0.56283 0.73158 0.86383 0.22001 anti-erbB2 0.0232 0.0013 <-0001 0.4129
16 16 16 16 var76 0.56005 0.73956 0.87890 0.22946 anti-VEGF 0.0241 0.0011 <.0001 0.3926
16 16 16 16 var77 0.48453 0.59036 0.79045 0.31338 anti-alpha synuclein 0.0572 0.0161 0.0003 0.2372
16 16 16 16 var78 0.85582 0.49980 0.52267 0.68430 anti-mucin-1 <.0001 0.0487 0.0378 0.0035
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var8 var9 varlO varll var67 0.22358 0.61173 0.62043 -0.12295 anti-c-jun 0.4052 0.0118 0.0103 0.6501
16 16 16 16 var68 0.28187 0.68536 0.66200 0.28796 anti-Fra-2 0.2902 0.0034 0.0052 0.2795
16 16 16 16 var69 -0.02999 0.02069 0.00619 -0.14467 anti-Fra-1 0.9122 0.9394 0.9819 0.5929
16 16 16 16 var70 0.63683 0.61494 0.59467 0.52735 anti-Jun B 0.0080 0.0112 0.0151 0.0358
16 16 16 16 var71 0.62878 0.63529 0.61156 0.53343 anti-P-c-Jun 0.0091 0.0082 0.0118 0.0333
16 16 16 16 var72 0.71910 0.86242 0.84872 0.56131 anti-TGase3 0.0017 <.0001 <.0001 0.0237
16 16 16 16 var74 0.6S374 0.47162 O .44842 0.73061 anti-PSA 0.005α 0.0651 0.0815 0.0013
16 16 16 16 var75 0.65906 0.61180 0.55131 0.80934 anti-erbB2 0.0055 0.0118 0.0269 0.0001
16 16 16 16 var76 0.66896 0.60457 0.54822 0.79478 anti-VEGP O.0046 0.0131 0.0279 0.0002
16 16 16 16 var77 0.69043 0.46893 0.47549 0.42272 anti-alpha synuclein 0.0031 0.0669 0.0627 0.1028
16 16 16 16 var78 0.81845 0.79248 0.85780 0.11622 anti-mucin-1 0.0001 0.0003 <.0001 0.6682
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations varl2 varl3 varl4 varl5 var67 0.61679 0.54280 -0.07247 0.13983 anti-c-jun 0.0109 0.0298 0.7897 0.6055
16 16 16 16 var68 0.68076 0.63080 -0.04889 0.25971 anti-Fra-2 0.0037 0.0088 0.8573 0.3314
16 16 16 16 var69 0.02136 0.05276 -0.12048 -0.30785 anti-Fra-1 0.9374 0.8461 0.6567 0.2461
16 16 16 16 var70 0.58554 0.88222 0.04499 0.27441 anti-Jun B 0.0172 <.0001 0.8686 0.3037
16 16 16 16 var71 0.60999 0.88359 0.05231 0.28576 anti-P-c-Jun 0.0121 <.0001 0.8474 0.2833
16 16 16 16 var72 0.84298 0.93997 0.19567 0.44217 anti-TGase3 <.0001 <.0001 0.4677 0.0864
16 16 16 16 var74 0.43762 0.80426 0.11001 0.34622 anti-PSA 0.0900 0.0002 0.6851 0.1890
16 16 16 16 var75 0.56604 0.87246 0.10048 0.34367 anti-erbB2 0.0223 <.0O01 0.7112 0.1925
16 16 16 16 var76 0.55961 0.87311 0.11127 0.35154 anti-VEGF 0.0242 <.0001 0.6816 0.1818
16 16 16 16 var77 0.44101 0.69810 0.22494 0.36223 anti-alpha synuclein 0.0873 0.0026 0.4023 0.1680
16 16 16 16 var78 0.79527 0.71497 0.50326 0.59035 anti-mucin-1 0.0002 0.0019 0.0469 0.0161
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations varlδ varl7 varlβ varl9 var67 0.53706 0.57283 0.59441 0.57943 anti-c-jun 0.0319 0.0204 0.0152 0.0187
16 16 16 16 varS8 0.51260 0.68478 0.68035 0.63805 anti-Fra-2 0.0423 0.0034 0.0037 0.0078
16 16 16 16 varS9 0.04334 -0.00357 -0.01090 0.02177 anti-Fra-1 0.8734 0.9895 0.9680 0.9362
16 16 16 16 var70 0.50985 0.64988 0.64786 0.51604 anti-Jun B 0.0436 0.0064 0.0067 0.0407
16 16 16 16 var71 0.52495 0.66178 0.65806 0.56163 anti-P-c-Jun 0.0368 0.0052 0.0056 0.0236
16 16 16 16 var72 0.77323 0.91075 0.89750 0.78679 anti-TGase3 0.0004 <.00Ol <-0001 0.0003
16 16 16 16 var74 0.36799 0.53769 0.52524 0.38440 anti-PSA 0.1608 0.0317 0.0367 0.1415
16 16 16 16 var75 0.48110 0.67662 0.63523 0.47099 anti-erbB2 0.0592 0.0040 0.0082 0.0656
16 16 IS 16 var76 0.47763 0.67179 0.63172 0.46544 anti-VEGF 0.0613 0.0044 0.0087 0.0692
16 16 16 16 var77 0.43650 0.52593 0.51696 0.38149 anti-alpha synuclein 0.0909 0.0364 0.0403 0.1448
16 16 16 16 var78 0.85528 0.84006 0.85031 0.78820 anti-mu.cin-1 <.00Ol <.0001 <.0001 0.0003
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var20 var21 var22 var23 var67 0.59244 0.36744 0.28597 0.25046 anti-c-jun 0.0156 0.1615 0.2829 0.3495
16 16 16 16 var68 0.56903 0.47412 0.47689 0.32901 anti-Fra-2 0.0214 0.0635 0.0618 0.2134
16 16 16 16 var69 0.02165 0.10728 -0.04982 -0.07514 anti-Fra-1 0.9366 0.6925 0.8546 0.7821
16 16 16 16 var70 0.52308 0.92718 0.20565 0.36143 anti-Jun B 0.0376 <.0001 0.4448 0.1690
16 16 16 16 var71 0.50688 0.95053 0.21673 0.37019 anti-P-c-Jun 0.0451 <.0001 0.4201 0.1581
16 16 16 16 var72 0.76413 0.81840 0.50831 0.54559 anti-TGase3 0.0006 0.0001 0.0444 0.0288 is 16 16 16 var74 0.35149 0.95978 0.27408 0.38757 ant i- PSA 0.1819 <.0001 0.3043 0.1380 16 16 16 16 var75 0.42577 0.86533 0.25279 0.42549 anti-erbB2 0.1001 <-0001 0.3449 0.1004 16 16 16 16 var76 0.42849 0.87340 0.28089 0.42965 anti-VEGF 0.0977 <.0001 0.2920 0.0967 16 16 16 16 var77 0.42877 0.75787 0.12496 0.49909 anti-alpha synuclein 0.0975 0.0007 0.6447 0.0491 16 16 16 16 var78 0.86762 0.50976 0.31054 0.68348 anti-mucin-1 <.0001 0.0437 0.2418 0.0035 16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var24 var25 var26 var27 var67 0.58568 0.57325 0.52746 0.62351 anti-c-jun 0.0171 0.0203 0.0358 0.0099
16 16 16 16 var68 0.72257 0.64678 0.67135 0.65394 anti-Fra-2 0.0016 0.0068 0.0044 0.0060
16 16 16 16 var69 -0.01632 -0.00277 -0.02433 0.00476 anti-Fra-1 0.9522 0.9919 0.9287 0.9860
16 16 16 16 var70 0.47125 0.62094 0.65707 0.61487 anti-Jun B 0.0654 0.0103 0.0057 0.0113
16 16 16 16 var71 0.49907 0.62795 0.67456 0.62615 anti-P-c-Jun 0.0491 0.0092 0.0042 0.0095
16 16 16 16 var72 0.80477 0.88124 0.91710 0.85460 anti-TGase3 0.0002 <.0001 <.0001 <.0001
16 16 16 16 var74 0.39007 0.49981 0.57436 0.46607 anti-PSA 0.1353 0.0487 0.0200 0.0688
16 16 16 16 var75 0.47632 0.59027 0.66022 0.56387 anti-erbB2 0.0622 0.0161 0.0054 0.0229
16 16 16 16 var76 0.47975 0.58972 0.65849 0.56222 anti-VEGF 0.0600 0.0162 0.0055 0.0234
16 16 16 16 var77 0.38345 0.51624 0.52604 0.49485 anti-alpha synuclein 0.1426 0.0406 0.0363 0.0513
16 16 16 16 var78 0.73429 0.89379 0.85524 0.86565 anti-mucin-1 0.0012 <.0001 •s.OOOl <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var28 var29 var30 var31 var67 -0.17081 -0.08778 0.11340 0.07338 anti-c-jun 0.5271 0.7465 0.6758 0.7871
16 16 16 16 var68 0.16420 0.16111 0.13694 0.11746 anti-Fra-2 0.5434 0.5511 0.6131 0.6648
16 16 16 16 varS9 -0.11775 -0.07612 -0.05449 -0.03480 anti-Fra-1 0.6641 0.7793 0.8411 0.8982
16 16 16 16 var70 0.43094 0.38816 0.27936 0.32948 anti-Jun B 0.0956 0.1374 0.2947 0.2127
16 16 16 16 var71 0.47471 0.35087 0.28579 0.32729 anti-P-c-Jun 0.0632 0.1827 0.2833 0.2159
16 16 16 16 var72 0.47191 0.40126 0.43645 0.45442 anti-TGase3 0.0650 0.1235 0.0910 0.0770
16 16 16 16 var74 0.67016 0.48158 0.30589 0.38207 anti-PSA 0.0045 0.0589 0.2492 0.1442
16 16 16 16 var75 0.65566 0.70844 0.32558 0.39411 anti-erbB2 0.0058 0.0021 0.2185 0.1309
16 16 16 16 var76 0.64894 0.69568 0.33665 0.40391 anti-VEGF 0.0065 0.0028 0.2023 0.1208
16 16 16 16 var77 0.46085 0.36963 0.43507 0.50848 anti-alpha synuclein 0.0724 0.1588 0.0921 0.0443
16 16 16 16 var78 0.22928 0.06561 0.67583 0.67640 anti-mucin-1 0.3930 0.8092 0.0041 0.0040
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var32 var33 var34 var35 var67 -0.40034 0.59336 0.53830 0.46208 anti-c-jun 0.1244 0.0154 0.0315 0.0715
16 16 16 16 var68 -0.09636 0.68759 0.67100 0.49240 anti-Fra-2 0.7226 0.0032 0.0044 0.0527
16 16 16 16 var69 0.19049 0.00431 0.00817 -0.01213 anti-Fra-1 0.4798 0.9874 0.9760 0.9644
16 16 16 16 var70 -0.07057 0.63168 0.56866 0.16099 anti-Jun B 0.7951 0.0087 0.0215 0.5514
16 16 16 16 var71 0.00714 0.63974 0.60927 0.15738 anti-P-c-Jun 0.9791 0.0076 0.0122 0.5605
16 16 16 16 var72 0.00418 0.88551 0.82439 0.40197 anti-TGase3 0.9878 <.0001 <.0001 0.1227
16 16 16 16 var74 0.13563 0.49700 0.47641 -0.00462 anti-PSA 0.6165 0.0502 0.0621 0.9864
16 16 16 16 var7S 0.08541 0.65905 0.53106 0.10186 anti-erbB2 0.7531 0.0055 0.0343 0.7074
16 16 16 16 var76 0.08062 0.65121 0.52236 0.08856 anti-VEGF 0.7666 0.0063 0.0379 0.7443
16 16 16 16 var77 0.02011 0.49786 0.39315 -0.03366 anti-alpha synuclein 0.9411 0.0497 0.1319 0.9015
16 16 16 16 var78 0.07247 0.80448 0.73783 0.39892 anti-mucin-1 0.7897 0.0002 0.0011 0.1259
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var36 var37 var38 var39 var67 0.58688 0.55732 0.22510 0.61853 anti-c-jun 0.0169 0.0249 0.4019 0.0106
16 16 16 16 var68 0.65348 0.67599 0.38560 0.67970 anti-Fra-2 0.0060 0.0040 0.1402 0.0038
16 16 16 16 var69 0.01906 -0.01488 -0.06376 0.01856 anti-Fra-1 0.9441 0.9564 0.8145 0.9456
16 16 16 16 var70 0.52190 0.66884 0.52937 0.58468 anti-Jun B 0.0381 0.0046 0.0350 0.0174
16 16 16 16 var71 0.56091 0.66114 0.60600 0.60159 anti-P-c-Jun 0.0238 0.0053 0.0128 0.0137
16 16 16 16 var72 0.79553 0.92486 0.55741 0.84468 anti-TGase3 0.0002 <.0001 0.0249 <.0001
16 16 16 16 var74 0.38484 0.56197 0.59716 0.43122 anti-PSA 0.1411 0.0235 0.0146 0.0954
16 16 16 16 var75 0.47475 0.67289 0.57319 0.57358 anti-erbB2 0.0631 0.0043 0.0203 0.0202
16 16 16 16 var76 0.46956 0.67125 0.56879 0.56694 anti-VEGF 0.0665 0.0044 0.0215 0.0220
16 16 16 16 var77 0.37564 0.54232 0.38141 0.44786 anti-alpha synuclein 0.1516 0.0300 0.1449 0.0819
16 16 16 16 var78 0.78821 0.86844 0.28150 0.80386 anti-tnucin-1 0.0003 <.O001 0.2909 0.0002
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var40 var41 var42 var43 var67 0.37484 0.52505 0.61100 0.64056 anti-c- jun 0.1526 0.0368 0.0119 0.0075
16 16 16 16 var68 0.57783 0.60023 0.66437 0.68247 anti-Fra-2 0.0191 0.0140 0.0050 0.0036
16 16 16 16 var69 -0.03795 0.03180 0.00912 0.03521 anti-Fra-1 0.8890 0.9069 0.9732 0.8970
16 16 16 16 var70 0.71784 0.92170 0.49813 0.45243 ant i -Jun B 0.0017 <.0001 0.0496 0.0785
16 16 16 16 var71 0.74462 0.92003 0.49451 0.48240 ant i- P- c -Jun 0.0009 <.0001 0.0515 0.0584
16 16 16 16 var72 0.84932 0.92626 0.77917 0.75966 anti-TGase3 <.0001 <.0001 0.0004 0.0006
16 16 16 16 var74 0.70504 0.86168 0.35303 0.30614 ant i- PSA 0.0023 <.0001 0.1798 0.2488
16 16 16 16 var75 0.85909 0.86838 0.47794 0.40103 anti-erbB2 <.0001 <.0001 0.0611 0.1237
16 16 16 16 var7S 0.84900 0.87437 0.48662 0.40507 anti-VEGF <.0001 <.0001 0.0559 0.1196
16 16 16 16 var77 0.54431 0.71124 0.27216 0.29781 anti-alpha synuclein 0.0293 0.0020 0.3079 0.2626
16 16 16 16 var78 0.53796 0.69320 0.63578 0.71350 anti-mucin-1 0.0316 0.0029 0.0081 0.0019
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var45 var46 var47 var48 var67 0.15609 -0.11290 0.44538 0.09024 anti-c-jun 0.5638 0.6772 0.0838 0.7396
16 16 16 16 var68 0.03199 -0.14114 0.68313 0.25463 anti-Fra-2 0.9064 0.6021 0.0035 0.3412
16 16 16 16 var69 0.61706 -0.08724 -0.01994 0.20353 anti-Fra-1 0.0109 0.7480 0.9416 0.4496
16 16 16 16 var70 0.09202 0.18374 0.59535 0.81952 anti-Jun B 0.7346 0.4958 0.0150 0.0001
16 16 16 16 var71 0.12469 0.19963 0.67700 0.85037 anti-P-c-Jun 0.6454 0.4585 0.0040 <.0001
16 16 16 16 var72 0.1730S 0.25847 0.74752 0.67561 anti-TGase3 0.5215 0.3337 0.0009 0.0041
16 16 16 16 var74 0.01481 0.26942 0.58474 0.94262 anti-PSA 0.9566 0.3129 0.0174 <.0001
16 16 16 16 var75 0.01809 0.26907 0.65180 0.88988 anti-erbB2 0.9470 0.3136 0.0062 <.0001
16 16 16 16 var76 0.02818 0.27840 0.62342 0.89675 anti-VEGF 0.9175 0.2964 0.0099 <.0001
16 16 16 16 var77 0.16908 0.38657 0.41490 0.70586 anti-alpha synuclein 0.5313 0.1391 0.1100 0.0022
16 16 16 16 var78 0.15344 0.50589 0.49555 0.26571 anti-mucin-1 0.5705 0.045S 0.0509 0.3199
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var49 var50 var51 var52 var67 0.32675 0.40296 0.54828 0.58958 anti-c-jun 0.2167 0.1217 0.0279 0.0162
16 16 16 16 var68 0.44265 0.58801 0.57999 0.64506 anti-Fra-2 0.0860 0.0166 0.0185 0.0070
16 16 16 16 var69 0.10389 -0.00506 -0.09538 -0.00870 anti-Fra-1 0.7018 0.9852 0.7253 0.9745
16 16 16 16 var70 0.92782 0.58111 0.54414 0.65303 anti-Jun B <.0001 0.0182 0.0293 0.0061
16 16 16 16 var71 0.944S3 0.56372 0.50852 0.64939 anti-P-c-Jun <.0001 0.0230 0.0443 0.0065
16 16 16 16 var72 0.73885 0.80211 0.83541 0.88081 anti-TGase3 0.0011 0.0002 <.0001 •=.0001
16 16 16 16 var74 0.96775 0.49822 0.42540 0.52156 anti-PSA <.0001 0.0495 0.1004 0.0383
16 16 16 16 var75 0.93214 0.75929 0.55778 0.62885 anti-erbB2 <-0001 0.0006 0.0248 0.0091
16 16 16 16 var76 0.93101 0.74504 0.56584 0.62684 anti-VEGF <.0001 0.0009 0.0223 0.0094
16 16 16 16 var77 0.77642 0.47244 0.50537 0.53718 anti-alpha synuclein 0.0004 0.0646 0.0458 0.0319
16 16 16 16 var78 0.34132 0.59779 0.90986 0.86032 anti-mucin-1 0.1957 0.0145 <.0O01 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : RhO=O Number of Observations var53 var54 var55 varSβ var67 0.52193 -0.01937 0.28581 0.45138 anti-c-jun 0.0381 0.9432 0.2832 0.0793
16 16 16 16 var68 0.50456 0.08509 0.51984 0.60675 anti-Fra-2 0.0462 0.7540 0.0390 0.0127
16 16 16 16 var69 -0.01548 -0.07009 -0.05479 0.00325 anti-Fra-1 0.9546 0.7965 0.8403 0.9905
16 16 16 16 var70 0.47787 0.30717 0.65955 0.57872 anti-Jun B 0.0612 0.2472 0.0054 0.0188
16 16 16 16 var71 0.47727 0.18028 0.69882 0.57067 anti-P-c-Jun 0.0616 0.5040 0.0026 0.0210
16 16 16 16 var72 0.75281 0.35546 0.75765 0.80475 anti-TGase3 0.0008 0.1767 0.0007 0.0002
16 16 16 16 var74 0.34116 0.30294 0.69171 0.47378 anti-PSA 0.1960 0.2541 0.0030 0.0638
16 16 16 16 var75 0.41420 0.51025 0.83699 0.72972 anti-erbB2 0.1107 0.0434 <.0001 0.0013
16 16 16 16 var76 0.41974 0.50961 0.82510 0.71552 anti-VEGF 0.1055 0.0438 <-0001 0.0018
16 16 16 16 var77 0.45260 0.36926 0.50350 0.45613 anti-alpha synuclein 0.0783 0.1593 0.0468 0.0758
16 16 16 16 var78 0.94832 0.29946 0.38861 0.61788 anti-mucin-1 <.0001 0.2598 0.1369 0.0107
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var57 var58 var59 var60 var67 0.42942 0.46419 0.32669 0.33378 anti-c-jun 0.0969 0.0701 0.2168 0.2064
16 16 16 16 var68 0.55575 0.49802 0.63146 0.50861 anti-Fra-2 0.0254 0.0496 0.0087 0.0442
16 16 16 16 var69 0.02781 -0.06297 -0.05854 0.00376 anti-Fra-1 0.9186 0.8168 0.8295 0.9890
16 16 16 16 var70 0.84444 0.89584 0.70912 0.54484 anti-Jun B <.0001 <.0001 0.0021 0.0291
16 16 16 16 var71 0.90991 0.87850 0.74740 0.51836 anti-P-c-Jun <.0001 <.0001 0.0009 0.0397
16 16 16 16 var72 0.73000 0.76428 0.89142 0.72224 anti-TGase3 0.0013 0.0006 ■=.0001 0.0016
16 16 16 16 var74 0.88747 0.89351 0.76310 0.47301 anti-PSA <.0001 ■=.0001 0.0006 0.0643
16 16 16 16 var75 0.79198 0.86957 0.79359 0.75358 anti-erbB2 0.0003 <.0001 0.0002 0.0007
16 16 16 16 var76 0.78583 0.87507 0.78309 0.73853 anti-VEGF 0.0003 <.0001 0.0003 0.0011
16 16 16 16 var77 0.70117 0.89094 0.53380 0.45899 anti-alpha synuclein 0.0025 ■=.0001 0.0332 0.0737
16 16 16 16 var78 0.39071 0.58729 0.61025 0.49864 anti-mucin-1 0.1346 0.0168 0.0121 0.0493
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var61 var62 var63 var64 var67 0.43060 0.31603 0.57403 0.62785 anti-c-jun 0.0959 0.2331 0.0201 0.0092
16 16 16 16 var68 0.65134 0.55917 0.67873 0.66180 anti-Fra-2 0.0063 0.0243 0.0038 0.0052
16 16 16 16 var69 -0.02920 -0.06574 0.02782 0.03215 anti-Fra-1 0.9145 0.8089 0.9185 0.9059
16 16 16 16 var70 0.58184 0.71290 0.81662 0.54616 anti-Jun B 0.0181 0.0019 0.0001 0.0286
16 16 16 16 var71 0.62968 0.76943 0.84772 0.56677 anti-P-c-Jun 0.0089 0.0005 ■=.0001 0.0221
16 16 16 16 var72 0.83652 0.82913 0.93618 0.80233 anti-TGase3 <.0001 <.0001 <.0001 0.0002
16 16 16 16 var74 0.55563 0.76474 0.74494 0.37788 anti-PSA 0.0254 0.0006 0.0009 0.1490
16 16 16 16 var75 0.60228 0.71996 0.78812 0.50088 anti-erbB2 0.0136 0.0017 0.0003 0.0481
16 16 16 16 var76 0.59142 0.71531 0.78625 0.49419 anti-VEGF 0.0158 0.0018 0.0003 0.0517
16 16 16 16 var77 0.41005 0.47354 0.63812 0.40403 anti-alpha synuclein 0.1147 0.0639 0.0078 0.1206
16 16 16 16 var78 0.69006 0.55469 0.74530 0.79500 anti-mucin-1 0.0031 0.0257 0.0009 0.0002
16 16 16 16 Pearson Correlation Coef ficients Prob > | r] under HO : Rho=0 Number of Observations varθ5 varbb var67 var68 var67 0.59S57 0.46452 1.00000 0.76676 anti-c-jun 0.0147 0.0699 0.0005
IS 16 16 16 varS8 0.59293 0.64405 0.76676 1.00000 anti-Fra-2 0.0155 0.0071 0.0005
16 16 IS 16 var69 0.33185 -0.02559 -0.13175 -0.29226 anti-Fra-1 0.2092 0.9251 0.62S7 0.2720
16 16 16 16 var70 0.7S280 0.72691 0.56617 0.53562 anti-Jun B 0.0006 0.0014 0.0222 0.0325
16 16 16 16 var71 0.83777 0.78142 0.54104 0.52181 anti-P-c-Jun <.0001 0.0004 0.0305 0.0382
16 16 IS 16 var72 0.77382 0.88560 0.48876 0.70922 anti-TGase3 0.0004 <.0001 0.0547 0.0021
16 16 16 16 var74 0.67201 0.70205 0.29295 0.42164 anti-PSA 0.0044 0.0024 0.2708 0.1038
16 16 IS 16 var75 0.68335 0.71249 0.30795 0.51000 anti-erbB2 0.0035 0.0020 0.2459 0.0436
16 16 16 16 var76 0.67505 0.70754 0.31035 0.49665 anti-VEGF 0.0041 0.0022 0.2420 0.0504
16 16 IS 16 var77 0.74450 0.49117 0.46114 0.33127 anti-alpha synuclein 0.0009 0.0534 0.0722 0.2101
16 16 16 16 var78 0.62433 0.66492 0.47954 0.46075 anti-mucin-1 0.0097 0.0049 0.0602 0.0725
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var69 var70 var71 var72 var67 -0.13175 0.56617 0.54104 0.48876 anti-c-jun 0.S267 0.0222 0.0305 0.0547
16 16 IS 16 var68 -0.29226 0.53562 0.52181 0.70922 anti-Fra-2 0.2720 0.0325 0.0382 0.0021
16 16 16 16 var69 1.00000 0.03601 0.11862 -0.07256 anti-Fra-1 0.8947 0.6617 0.7894
16 16 16 16 var70 0.03601 1.00000 0.97573 0.79618 anti-Jun B 0.8947 <.0001 0.0002
16 16 16 16 var71 0.11862 0.97573 1.00000 0.77619 anti-P-c-Jun 0.6617 <.0001 0.0004
16 16 16 16 var72 0.07256 0.79618 0.77619 1.00000 anti-TGase3 0.7894 0.0002 0.0004
IS 16 16 16 var74 0.03758 0.93345 0.92860 0.77729 anti-PSA 0.8901 <.0001 <.0001 0.0004
16 16 16 16 var75 0.00172 0.88568 0.87650 0.85269 anti-erbB2 0.9949 <.0001 <.0001 <.0001
16 16 16 16 var7S 0.00322 0.89535 0.87933 0.85869 anti-VEGF 0.9905 <.0001 <.0001 <.0001
16 16 16 16 var77 0.33185 0.83178 0.82926 0.62902 anti-alpha synuclein 0.2092 <-0001 <.0001 0.0090
16 16 16 16 var78 0.06278 0.52984 0.48846 0.76618 anti-mucin-1 0.8173 0.0348 0.0549 0.0005
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var74 var75 var76 var77 var67 0.29295 0.30795 0.31035 0.46114 anti-c-jun 0.2708 0.2459 0.2420 0.0722
16 16 16 16 var68 0.42164 0.51000 0.49665 0.33127 anti-Fra-2 0.1038 0.0436 0.0504 0.2101
16 16 16 16 var69 0.03758 -0.00172 0.00322 0.33185 anti-Fra-1 0.8901 0.9949 0.9905 0.2092
16 16 16 16 var70 0.93345 0.88568 0.89535 0.83178 anti-Jun B < .0001 <.0001 <.0001 <.0001
16 16 16 16 var71 0.92860 0.87650 0.87933 0.82926 anti-P-c-Jun <.0001 <.0001 <.0001 <.0001
16 16 16 16 var72 0.77729 0.85269 0.85869 0.62902 anti-TGase3 0.0004 <.0001 <.0001 0.0090
16 16 16 16 var74 1.00000 0.92707 0.93747 0.77992 anti-PSA <.0001 <.0001 0.0004
16 16 16 16 var75 0.92707 1.00000 0.99715 0.74590 anti-erbB2 <.0001 <.0001 0.0009
16 16 16 16 var76 0.93747 0.99715 1.00000 0.75325 anti-VEGF <.0001 <-0001 0.0008
16 16 16 16 var77 0.77992 0.74590 0.75325 1.00000 anti-alpha synuclein 0.0004 0.0009 0.0008
16 16 16 16 var78 0.41634 0.48545 0.49410 0.57147 anti-mucin-1 0.1087 0.0566 0.0517 0.0207
16 16 16 16 Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var78 var79 var80 varδl var67 0.47954 0.15778 0.33688 0.64166 anti-c-jun 0.0602 0.5595 0.2020 0.0181
IS 16 16 13 var68 0.46075 0.28408 0.48120 0.44750 anti-Fra-2 0.0725 0.2863 0.0591 0.1252
16 16 16 13 var69 -0.06278 0.08902 0.04308 -0.17828 anti-Fra-1 0.8173 0.7430 0.8741 0.5601
16 16 16 13 var70 0.52984 0.84617 0.94222 0.41560 anti-Jun B 0.0348 <-0001 <-0001 0.1578
16 16 16 13 var71 0.48846 0.86254 0.94450 0.34463 anti-P-c-Jun 0.0549 <.0001 <.0001 0.2489
16 16 16 13 var72 0.7S618 0.67008 0.82634 0.61774 anti-TGase3 0.0005 0.0045 <.0001 0.0245
16 16 16 13 var74 0.41634 0.95065 0.98876 0.27095 anti-PSA 0.1087 <.0001 ■=.0001 0.3706
16 16 16 13 var75 0.48545 0.87365 0.96072 0.26561 anti-erbB2 0.0566 <.0001 <.0001 0.3804
16 16 16 13 var76 0.49410 0.88261 0.96496 0.27819 anti-VEGF 0.0517 <.0001 <.0001 0.3574
16 16 16 13 var77 0.57147 0.73498 0.78772 0.42677 anti-alpha synuclein 0.0207 0.0012 0.0003 0.1458
16 16 16 13 var78 1.00000 0.31464 0.47320 0.86681 anti-mucin-1 0.2353 0.0641 0.0001
16 16 16 13
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var82 var83 var84 var85 var67 0.37159 0.61402 0.59378 0.39210 anti-c-jun 0.2112 0.0256 0.0324 0.1851
13 13 13 13 var68 0.37430 0.70749 0.67924 0.50449 anti-Fra-2 0.2077 0.0068 0.0107 0.0787
13 13 13 13 var69 0.45195 -0.02502 -0.02988 0.01338 anti-Fra-1 0.1210 0.9353 0.9228 0.9654
13 13 13 13 var70 0.77554 0.85275 0.65090 0.91975 anti-Jun B 0.0018 0.0002 0.0160 <.0001
13 13 13 13 var71 0.88482 0.85897 0.63550 0.90123 cuiuj.- f-c-uun <-0001 0.0002 0.0196 <.0001
13 13 13 13 var72 0.6S781 0.92509 0.80877 0.83565 anti-TGase3 0.0126 <-0001 0.0008 0.0004
13 13 13 13 var74 0.80487 0.81050 0.55723 0.94751 anti-PSA 0.0009 0.0008 0.0479 <.0001
13 13 13 13 var75 0.73352 0.94321 0.79128 0.99619 anti-erbB2 0.0043 <.0001 0.0013 <.0001
13 13 13 13 var76 0.73188 0.93182 0.77244 0.99832 anti-VEGF 0.0045 <.0001 0.0020 <.0001
13 13 13 13 var77 0.78437 0.73055 0.55244 0.81040 anti-alpha synuclein 0.0015 0.0046 0.0503 0.0008
13 13 13 13 var78 0.37276 0.61204 0.56517 0.46888 anti-raucin-1 0.2097 0.0262 0.0441 0.1060
13 13 13 13
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var86 var87 var88 var89 var67 0.30616 0.32378 0.18520 0.55294 anti-c-jun 0.2488 0.2391 0.5087 0.0325
16 15 15 15 varS8 0.26966 0.32604 0.12252 0.68480 anti-Fra-2 0.3125 0.2356 0.6636 0.0049
16 15 15 15 var69 0.34950 0.22719 0.00424 0.02419 anti-Fra-1 0.1845 0.4155 0.9880 0.9318
16 15 15 15 var70 0.86006 0.83933 0.23505 0.59769 anti-Jun B <.0001 <.0001 0.3991 0.0186
16 15 15 15 var71 0.90804 0.86254 0.11790 0.60951 anti-P-c-Jun <.0001 <.0001 0.6756 0.0159
16 15 15 15 var72 0.53956 0.59748 0.31152 0.83985 anti-TGase3 0.0310 0.0187 0.2584 <.0001
16 15 15 15 var74 0.86642 0.79718 0.13236 0.45863 anti-PSA <.0001 0.0004 0.6382 0.0855
16 15 15 15 var75 0.79197 0.80613 0.14755 0.67165 anti-erbB2 0.0003 0.0003 0.5997 0.0061
16 15 15 15 var76 0.79127 0.81229 0.15681 0.65948 anti-VEGF 0.0003 0.0002 0.5768 0.0075
16 15 15 15 var77 0.78131 0.64579 0.32006 0.45934 anti-alpha synuclein 0.0004 0.0093 0.2448 0.0850
16 15 15 15 var78 0.19213 0.21806 0.58223 0.70499 anti-mucin-1 0.4759 0.4350 0.0228 0.0033 16 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var90 var91 var92 var93 varS7 0.5069S 0.55416 0.53638 0.61175 anti-c-jun 0.0538 0.0321 0.0322 0.0118
15 15 16 16 var68 0.53034 0.69375 0.60305 0.64438 anti-Fra-2 0.0420 0.0041 0.0134 0.0071
15 15 16 16 varS9 -0.01252 0.09838 0.08803 0.03360 anti-Fra-1 0.9647 0.7272 0.7458 0.9017
15 15 16 16 var70 0.41728 0.71321 0.67887 0.52584 anti-Jun B 0.1217 0.0028 0.0038 0.0364
15 15 16 16 var71 0.46588 0.75622 0.65157 0.55874 anti-P-c-Jun 0.0801 0.0011 0.0053 0.0245
15 15 16 16 var72 0.70872 0.89462 0.83460 0.78943 anti-TGase3 0.0031 <.0001 <.0001 0.0003
15 15 16 16 var74 0.28355 0.62473 0.54461 0.36999 anti-PSA 0.3058 0.0128 0.0292 0.1584
15 15 16 16 var75 0.38415 0.70883 0.76073 0.47032 anti-erbB2 0.1575 0.0031 0.0006 0.0660
15 15 16 16 var76 0.38121 0.70037 0.75113 0.46559 anti-VEGF 0.1609 0.0036 0.0008 0.0S91
15 15 16 16 var77 0.33650 0.60770 0.60732 0.38812 anti-alpha synuclein 0.2201 0.0163 0.0126 0.1374
15 15 16 16 var78 0.80854 0.76806 0.70411 0.79565 anti-mucin-1 0.0003 0.0008 0.0023 0.0002
15 15 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
Capture varl var2 var3 var79 0.77586 0.81681 0.41588 0.31976 anti-Cystatin A 0.0004 0.0001 0.1091 0.2273
16 16 16 16 var80 0.92726 0.94615 0.60073 0.51284 anti-Cystatin S <.0001 <.0001 0.0139 0.0422
16 16 16 16 var81 0.40299 0.40855 0.69511 0.77714 Prostein 0.1721 0.1657 0.0084 0.0018
13 13 13 13 var82 0.68495 0.77161 0.61683 0.53139 Aquaporin 4 0.0098 0.0020 0.0247 0.0616
13 13 13 13 var83 0.93635 0.93032 0.79740 0.73836 Trypsin •=.0001 <.0001 0.0011 0.0039
13 13 13 13 var84 0.83437 0.78479 0.73270 0.70511 Osteonectin 0.0004 0.0015 0.0044 0.0071
13 13 13 13 var85 0.96109 0.93519 0.58442 0.50913 RAGE ■=.0001 <.0001 0.0359 0.0756
13 13 13 13 var86 0.83523 0.80522 0.38817 0.29482 PGRP-I Beeta <.0001 0.0002 0.1374 0.2677
16 16 16 16 var87 0.73230 0.81257 0.47010 0.39007 PGRP-S 0.0019 0.0002 0.0770 0.1506
15 15 15 15 var88 0.20993 0.19853 0.29036 0.41067
Gram positive bacteria 0.4527 0.4781 0.2938 0.1284
15 15 15 15 var89 0.65948 0.75658 0.91093 0.89759
Troponin C Cardiac 0.0075 0.0011 .= .0001 <.0001
15 15 15 15
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var4 var5 varδ var7 var79 0.35929 0.72880 0.88030 0.13304 anti-Cystatin A 0.1717 0.0014 <.0001 0.6233
16 16 16 16 var80 0.54530 0.71339 0.95302 0.20478 anti-Cystatin S 0.0289 0.0019 ■=.0001 0.4468
16 16 16 16 var81 0.72543 0.18341 0.39801 0.32499 Prostein 0.0050 0.5487 0.1780 0.2786
13 13 13 13 var82 0.58096 0.52732 0.80693 0.18374 Aquaporin 4 0.0373 0.0640 0.0009 0.5479
13 13 13 13 var83 0.76321 0.62196 0.77498 0.28352 Trypsin 0.0024 0.0232 0.0019 0.3479
13 13 13 13 var84 0.71362 0.41579 0.54191 0.23791 Osteonectin 0.0062 0.1576 0.0557 0.4338
13 13 13 13 var85 0.53623 0.73554 0.87345 0.22248 RAGE 0.0589 0.0042 <.0001 0.4650
13 13 13 13 var86 0.33832 0.44373 0.86399 0.03687 PGRP-I Beeta 0.1999 0.0851 •=.0001 0.8922
16 16 16 16 var87 0.43573 0.42901 0.79661 0.04733 PGRP-S 0.1045 0.1106 0.0004 0.8670
15 15 15 15 var88 0.33465 0.02229 0.20360 -0.02347
Gram positive bacteria 0.2228 0.9372 0.4667 0.9338
15 15 15 15 var89 0.90955 0.33604 0.52020 0.35640 Troponin C Cardiac <.0001 0.2207 0.04S8 0.1923
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var8 var9 varlO varll var79 0.588S0 0.36059 0.33502 0.71412 anti-Cystatin A 0.0165 0.1700 0.2046 0.0019
16 16 16 16 var80 0.57966 0.56088 0.52908 0.73756 anti-Cystatin S 0.0038 0.0238 0.0351 0.0011
16 16 16 16 var81 0.52456 0.64036 0.72315 -0.06200 Prostein 0.0657 0.0184 0.0052 0.8405
13 13 13 13 var82 0.50253 0.58738 0.55925 0.48047 Aquaporin 4 0.0801 0.0348 0.0469 0.0965
13 13 13 13 var83 0.61969 0.82489 0.75638 0.74094 Trypsin 0.0239 0.0005 0.0028 0.0038
13 13 13 13 var84 0.47941 0.80677 0.72029 0.62320 Osteonectin 0.0974 0.0009 0.0055 0.0229
13 13 13 13 var85 0.63289 0.59061 0.52326 0.84541 RAGE 0.0203 0.0336 0.0665 0.0003
13 13 13 13 var86 0.46995 0.37861 0.32913 0.56056 PGRP-I Beeta 0.0662 0.1482 0.2132 0.0239
16 16 16 16 var87 0.38155 0.49897 0.42311 0.44995 PGRP-S 0.1605 0.0583 0.1161 0.0924
15 15 15 15 var88 0.24761 0.26989 0.33066 -0.04510
Gram positive bacteria 0.3736 0.3306 0.2287 0.8732
15 15 15 15 var89 0.51022 0.96468 0.91407 0.30534
Troponin C Cardiac 0.0520 <.0001 <.0001 0.2684
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations varl2 varl3 varl4 varl5 var79 0.33210 0.69272 0.07602 0.30459 anti-Cystatin A 0.2089 0.0029 0.7796 0.2514
16 16 16 16 var80 0.52599 0.85821 0.10254 0.35054 anti-Cystatin S 0.0364 <.0001 0.7055 0.1831
16 16 16 16 varδl 0.65660 0.52857 0.15805 0.29365 Prostein 0.0148 0.0633 0.6061 0.3302
13 13 13 13 var82 0.58147 0.74321 0.01497 0.18582 Aquaporin 4 0.0371 0.0036 0.9613 0.5433
13 13 13 13 var83 0.78973 0.93526 0.06883 0.31994 Trypsin 0.0013 <.0001 0.8232 0.2866
13 13 13 13 var84 0.7S447 0.83087 0.02500 0.20383 Osteonectin 0.0023 0.0004 0.9354 0.5042
13 13 13 13 var85 0.54763 0.85037 0.08346 0.32036 RAGE 0.0527 0.0002 0.78S3 0.2859
13 13 13 13 var86 0.34180 0.70610 -0.03169 0.10780 PGRP-I Beeta 0.1951 0.0022 0.9073 0.6911
16 16 16 16 var87 0.46955 0.76052 -0.11296 0.05410 PGRP-S 0.0774 0.0010 0.6885 0.8481
15 15 15 15 var88 0.27249 0.24316 -0.10412 -0.06559
Gram positive bacteria 0.3258 0.3825 0.7119 0.8163
15 15 15 15 var89 0.94643 0.88401 0.07838 0.24146
Troponin C Cardiac <.0001 <.O001 0.7813 0.3860
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations varl6 varl7 varl8 varl9 var79 0.27119 0.42274 0.42984 0.26669 anti-Cystatin A 0.3096 0.1028 0.0966 0.3181
16 16 16 16 var80 0.44790 0.62217 0.60672 0.46019 anti-Cystatin S 0.0819 0.0101 0.0127 0.0729
16 16 16 16 var81 0.79691 0.65764 0.73338 0.61900 Prostein 0.0011 0.0146 0.0043 0.0241
13 13 13 13 var82 0.47235 0.59570 0.61132 0.54441 Aquaporin 4 0.1031 0.0317 0.0264 0.0544
13 13 13 13 var83 0.69515 0.86010 0.82209 0.68372 Trypsin 0.0083 0.0002 0.0006 0.0100
13 13 13 13 var84 0.67323 0.82954 0.75999 0.65436 Osteonectin 0.0117 0.0005 0.0026 0.0152
13 13 13 13 var85 0.46406 0.65197 0.61289 0.43053 RAGE 0.1102 0.0157 0.0259 0.1420
13 13 13 13 var86 0.23497 0.40447 0.37087 0.30424 PGRP-I Beeta 0.3810 0.1202 0.1573 0.2519
16 16 16 16 var87 0.32721 0.50226 0.48021 0.37976 PGRP-S 0.2339 0.0564 0.0700 0.1627
15 15 15 15 var88 0.38832 0.28902 0.38347 0.16249
Gram positive bacteria 0.1526 0.29S1 0.1583 0.5629
15 15 15 15 var89 0.85475 0.95925 0.92392 0.87793
Troponin C Cardiac <.0001 <.0001 <.0001 <.0001 15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var20 var21 var22 var23 var79 0.26034 0.89180 0.20353 0.28704 anti-Cystatin A 0.3301 <.0001 0.4496 0.2811
16 16 16 16 var80 0.42630 0.95676 0.28317 0.40430 anti-Cystatin S 0.0996 <.0001 0.2879 0.1204
16 16 16 16 var81 0.86955 0.38922 0.30684 0.32168 Prostein 0.0001 0.1887 0.3079 0.2838
13 13 13 13 var82 0.47022 0.88600 0.22772 0.25043 Aquaporin 0.1049 <.0001 0.4543 0.4092
13 13 13 13 var83 0.63508 0.81126 0.26621 0.42017 Trypsin 0.0197 0.0008 0.3793 0.1529
13 13 13 13 var84 0.59523 0.55610 0.19408 0.37841 Osteonectin 0.0319 0.0484 0.5252 0.2023
13 13 13 13 var85 0.41630 0.87178 0.22301 0.36884 RAGE 0.1571 0.0001 0.4640 0.2149
13 13 13 13 var86 0.19825 0.85636 0.05963 0.23780 PGRP-I Beeta 0.4617 <.0001 0.8264 0.3751
16 16 16 16 var87 0.31319 0.77212 0.07123 0.10912 PGRP-S 0.2557 0.0007 0.8009 0.6987
15 15 15 15 var88 0.58513 0.14609 -0.01943 -0.04305
Gram positive bacteria 0.0219 0.6034 0.9452 0.8789
15 15 15 15 var89 0.80639 0.54597 0.28179 0.40914
Troponin C Cardiac 0.0003 0.0352 0.3089 0.1299
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var24 var25 var26 var27 var79 0.30063 0.39160 0.46587 0.36281 anti-Cystatin A 0.2579 0.1336 0.0690 0.1672
16 16 16 16 var80 0.45887 0.57354 0.64315 0.54586 anti-Cystatin S 0.0738 0.0202 0.0072 0.0287
16 16 16 16 varδl 0.64069 0.75980 0.69004 0.74362 Prostein 0.0183 0.0026 0.0090 0.0036
13 13 13 13 var82 0.50640 0.57854 0.63416 0.57667 Aquaporin 4 0.0774 0.0383 0.0199 0.0391 13 13 13 13 var83 0.65650 0.77360 0.82640 0.76547 Trypsin 0.0148 0.0019 0.0005 0.0023
13 13 13 13 var84 0.59977 0.71544 0.74754 0.71446 Osteonectin 0.0303 0.0060 0.0033 0.0061
13 13 13 13 var85 0.44385 0.56577 0.63719 0.54498 RAGE 0.1287 0.0439 0.0192 0.0541
13 13 13 13 var86 0.21783 0.34017 0.40451 0.33571 PGRP-I Beeta 0.4177 0.1973 0.1202 0.2037
16 16 16 16 var87 0.31953 0.42678 0.48423 0.44580 PGRP-S 0.2457 0.1126 0.0674 0.0958
15 15 15 15 var88 0.23308 0.38751 0.29364 0.36860
Gram positive bacteria 0.4031 0.1536 0.2881 0.1764
15 15 15 15 var89 0.79133 0.89479 0.89956 0.90855
Troponin C Cardiac 0.0004 <.0001 <.0001 <.0001
15 15 15 15
Pearson Correlation Coefficients Prob > I r I under HO : RhO=O Number of Observations var28 var29 var30 var31 var79 0.67326 0.48866 0.24523 0.33280 anti-Cystatin 0.0043 0.0548 0.3600 0.2078
16 16 16 16 var80 0.65255 0.52424 0.31718 0.39030 anti-Cystatin 0.0061 0.0371 0.2313 0.1350
16 16 16 16 varδl -0.08034 -0.16507 0.30240 0.30984 Prostein 0.7942 0.5900 0.3153 0.3029
13 13 13 13 var82 0.47768 0.24791 0.22648 0.25167 Aquaporin 4 0.0988 0.4141 0.4568 0.4068
13 13 13 13 var83 0.52272 0.64874 0.32738 0.34773 Trypsin 0.0668 0.0165 0.2749 0.2443
13 13 13 13 var84 0.32356 0.67284 0.26638 0.26635 Osteonectin 0.2809 0.0117 0.3790 0.3791
13 13 13 13 var85 0.65713 0.73526 0.31167 0.36828 RAGE 0.0147 0.0042 0.2999 0.2157
13 13 13 13 var86 0.48755 0.40572 0.15923 0.21697 PGRP-I Beeta 0.0554 0.1190 0.5558 0.4196
16 16 16 16 var87 0.29018 0.48447 0.09587 0.10963 PGRP-S 0.2941 0.0672 0.7340 0.6973
15 15 15 15 var88 -0.20129 -0.03521 -0.01090 0.06935
Gram positive bacteria 0.4719 0.9009 0.9692 0.8060
15 15 15 15 var89 0.13548 0 38106 0.32655 0.28539
Troponin C Cardiac 0.6302 0 .1611 0.2349 0.3025
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var32 var33 var34 var35 var79 0.22819 0.38975 0.32359 -0.06996 anti-Cystatin A 0.3953 0.1356 0.2215 0.7968
16 16 16 16 var80 0.12247 0.58989 0.53765 0.06518 anti-Cystatin S 0.6514 0.0162 0.0317 0.8105
16 16 16 16 varδl -0.35933 0.65310 0.66785 0.29302 Prostein 0.2279 0.0155 0.0126 0.3313
13 13 13 13 var82 0.30626 0.58045 0.55573 0.19015 Aquaporin 4 0.3088 0.0375 0.0486 0.5338
13 13 13 13 var83 0.01168 0.86594 0.71543 0.32627 Trypsin 0.9698 0.0001 0.0060 0.2766
13 13 13 13 var84 -0.13013 0.85353 0.69032 0.37546 Osteonectin 0.6718 0.0002 0.0090 0.2062
13 13 13 13 var85 0.08622 0.64343 0.45952 0.07151 RAGE 0.7794 0.0177 0.1142 0.8164
13 13 13 13 var86 0.09605 0.38276 0.38397 -0.04561 PGRP-I Beeta 0.7235 0.1434 0.1420 0.8668
16 16 16 16 var87 0.00141 0.50955 0.35263 0.08464 PGRP-S 0.9960 0.0524 0.1974 0.7642
15 15 15 15 var88 -0.26377 0.31852 0.21694 0.09773
Gram positive bacteria 0.3422 0.2473 0.4374 0.7290
15 15 15 15 var89 -0.13603 0.97706 0.83898 0.56450
Troponin C Cardiac 0.6288 <.0001 <-0001 0.0284
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var36 var37 var38 var39 var79 0.26490 0.45077 0.74801 0.31572 anti-Cystatin A 0.3214 0.0797 0.0009 0.2336
16 16 16 16 var80 0.46234 0.63870 0.63416 0.52141 anti-Cystatin S 0.0714 0.0077 0.0083 0.0383
16 16 16 16 var81 0.63759 0.76235 0.19901 0.66136 Prostein 0.0191 0.0024 0.5145 0.0138
13 13 13 13 var82 0.54224 0.58882 0.78195 0.55451 Aquaporin 4 0.0556 0.0342 0.0016 0.0492
13 13 13 13 var83 0.69328 0.83978 0.57381 0.79934 Trypsin 0.0086 0.0003 0.0403 0.0010
13 13 13 13 var84 0.S6693 0.78811 0.24142 0.79374 Osteonectin 0.0128 0.0014 0.4268 0.0012
13 13 13 13 var85 0.44041 0.64893 0.59641 0.55462 RAGE 0.1320 0.0164 0.0314 0.0492
13 13 13 13 var86 0.29887 0.38401 0.40341 0.33880 PGRP-I Beeta 0.2608 0.1420 0.1213 0.1993
16 16 16 16 var87 0.38895 0.47218 0.58521 0.46107 PGRP-S 0.1519 0.0755 0.0219 0.0837
15 15 15 15 var88 0.19603 0.44464 0.05425 0.28806
Gram positive bacteria 0.4838 0.0968 0.8477 0.2978
15 15 15 15 var89 0.88780 0.91610 0.37059 0.95906
Troponin C Cardiac <.0001 <.0001 0.1739 <.0001
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var40 var41 var42 var43 var79 0.72491 0.75803 0.22022 0.19494 anti-Cystatin A 0.0015 0.0007 0.4125 0.4694
16 16 16 16 var80 0.78562 0.89735 0.42259 0.38563 anti-Cystatin S 0.0003 <.0001 0.1030 0.1402
16 16 16 16 var81 0.34493 0.53899 0.48653 0.62413 Prostein 0.2484 0.0573 0.0918 0.0226
13 13 13 13 var82 0.77606 0.76995 0.44387 0.48573 Aquaporin 4 0.0018 0.0021 0.1287 0.0924
13 13 13 13 var83 0.96451 0.89006 0.69609 0.63333 Trypsin <.0001 <.0001 0.0082 0.0201
13 13 13 13 var84 0.81173 0.73386 0.71876 0.61974 Osteonectin 0.0008 0.0043 0.0056 0.0239
13 13 13 13 var85 0.89335 0.84841 0.47375 0.38410 RAGE <.0001 0.0002 0.1020 0.1951
13 13 13 13 var86 0.54724 0.74193 0.26176 0.21049 PGRP-I Beeta 0.0282 0.0010 0.3274 0.4339
16 16 16 16 var87 0.75446 0.77645 0.43135 0.34784 PGRP-S 0.0012 0.0007 0.1084 0.2039
15 15 15 15 var88 0.15603 0.25603 0.08840 0.18804
Gram positive bacteria 0.5787 0.3570 0.7541 0.Ξ022 15 15 15 15 var89 0.826S5 0.79502 0.88031 0.84804
Troponin C Cardiac 0.0001 0.0004 <.0001 <.0001
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var45 var46 var47 var48 var79 -0.00012 0.26566 0.59261 0.97884 anti-Cystatin A 0.9996 0.3200 0.0156 <-0001
16 16 16 16 var80 0.02275 0.26363 0.66792 0.93991 anti-Cystatin S 0.9334 0.3239 0.0047 <.0001
16 16 16 16 var81 0.00114 0.20119 0.38017 0.07649 Prostein 0.9970 0.5098 0.2001 0.8039
13 13 13 13 var82 0.35636 0.14974 0.73157 0.87007 Aquaporin 4 0.2320 0.6254 0.0045 0.0001
13 13 13 13 var83 0.12338 0.19926 0.73000 0.73518 Trypsin 0.6880 0.5140 0.0046 0.0042
13 13 13 13 var84 0.14713 0.11299 0.55574 0.45914 Osteonectin 0.6315 0.7132 0.0486 0.1145
13 13 13 13 var85 0.00784 0.26233 0.58086 0.90005 RAGE 0.9797 0.3866 0.0374 <.0001
13 13 13 13 var86 0.16030 0.13209 0.46762 0.84744 PGRP-I Beeta 0.5531 0.6258 0.0678 <.0001
16 16 16 16 var87 0.13726 0.03988 0.51893 0.83109 PGRP-S 0.6257 0.8878 0.0475 0.0001
15 15 15 15 var88 -0.03433 -0.04472 0.14043 0.05417
Gram positive bacteria 0.9033 0.8743 0.6177 0.8479
15 15 15 15 var89 0.29108 0.11229 0.68753 0.38535
Troponin C Cardiac 0.2925 0.6903 0.0046 0.1561
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var49 var50 var51 var52 var79 0.89570 0.38623 0.31123 0.44672 anti-Cystatin A <.0001 0.1395 0.2406 0.0828
16 16 16 16 var80 0.96959 0.59303 0.49975 0.60360 anti-Cystatin S <.0001 0.0155 0.0487 0.0133
16 16 16 16 varδl 0.18516 0.36874 0.80630 0.78560 Prostein 0.5448 0.2150 0.0009 0.0015
13 13 13 13 var82 0.83489 0.45841 0.39339 0.60780 Aquaporin 4 0.0004 0.1152 0.1836 0.0276
13 13 13 13 var83 0.87109 0.92359 0.72892 0.81278 Trypsin 0.0001 <.0001 0.0047 0.0007
13 13 13 13 var84 0.67201 0.99926 0.71723 0.73689 Osteonectin 0.0119 <.0001 0.0058 0.0041
13 13 13 13 var85 0.96497 0.76211 0.56361 0.61991 RAGE <.0001 0.0025 0.0449 0.0238
13 13 13 13 var86 0.93391 0.42658 0.21207 0.34963 PGRP-I Beeta <.0001 0.0994 0.4304 0.1844
16 16 16 16 var87 0.82339 0.55534 0.33082 0.47719 PGRP-S 0.0002 0.0316 0.2284 0.0721
15 15 15 15 var88 0.04889 0.17754 0.45285 0.49315
Gram positive bacteria 0.8S26 0.5267 0.0901 0.0618
15 15 15 15 var89 0.51636 0.93840 0.82998 0.89537
Troponin C Cardiac 0.0488 <-0001 0.0001 <.0001
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var53 var54 var55 var56 var79 0.25123 0.27107 0.75701 0.36530 anti-Cystatin A 0.3480 0.3099 0.0007 0.1641
16 16 16 16 var80 0.4100S 0.34418 0.76376 0.57287 anti-Cystatin S 0.1147 0.1918 0.0006 0.0204
16 16 16 16 varδl 0.79761 0.27684 0.19666 0.39541 Prostein 0.0011 0.3598 0.5196 0.1811
13 13 13 13 var82 0.45228 0.00322 0.76988 0.48432 Aquaporin 4 0.1207 0.9917 0.0021 0.0935
13 13 13 13 var83 0.61167 0.49093 0.90512 0.92253 Trypsin 0.0263 0.0885 <.0001 <.0001
13 13 13 13 var84 0.56042 0.58324 0.72051 0.99179 Osteonectin 0.0464 0.0364 0.0055 <.0001
13 13 13 13 var85 0.40991 0.55211 0.87658 0.73830 RAGE 0.1642 0.0504 <.0001 0.0040
13 13 13 13 var86 0.17138 0.15341 0.53294 0.41392 PGRP-I Beeta 0.5257 0.5706 0.0335 0.1110
16 16 16 16 var87 0.26804 0.22091 0.74261 0.56501 PGRP-S 0.3341 0.4288 0.0015 0.0282
15 15 15 15 var88 0.41280 0.54954 0.06021 0.16775 Gram positive bacteria 0.1262 0.0338 0.8312 0.5501
15 15 15 15 var89 0.77965 0.32346 0.70362 0.96775
Troponin C Cardiac 0.0006 0.2396 0.0034 <.0001
15 15 IS 15
Pearson Correlation Coefficients Prob > I r I under HO : Rho=0 Number of Observations var57 var58 var59 var60 var79 0.83187 0.83022 0.S350S 0.37741 anti-Cystatin A <.0001 <.0001 0.0082 0.1496
16 16 16 16 var80 0.88875 0.89423 0.7973S 0.56517 anti-Cystatin S <.0001 <.0001 0.0002 0.0225
16 16 16 16 varδl 0.32083 0.41410 0.54952 0.26307 Prostein 0.2852 0.1595 0.0517 0.3852
13 13 13 13 var82 0.92573 0.71118 0.74624 0.40728 Aquaporin 4 <.0001 0.0064 0.0034 0.1672
13 13 13 13 var83 0.81050 0.83827 0.94484 0.89769 Trypsin 0.0008 0.0003 <.0001 <.0001
13 13 13 13 var84 0.53060 0.62366 0.82593 0.99065 Osteonectin 0.0621 0.0227 0.0005 <.0001
13 13 13 13 var85 0.81822 0.91534 0.80785 0.77195
RAGE 0.0006 <.0001 0.0008 0.0020
13 13 13 13 var86 0.81703 0.74754 0.60014 0.42452 PGRP-I Beeta 0.0001 0.0009 0.0140 0.1012
16 16 IS 16 var87 0.65221 0.67305 0.47145 0.56156 PGRP-S 0.0084 0.0060 0.0761 0.0294
15 15 15 15 var88 0.00616 0.18205 0.12895 0.14615
Gram positive bacteria 0.9826 0.5161 0.6469 0.6032
15 15 15 15 var89 0.47210 0.51410 0.71475 0.87270
Troponin C Cardiac 0.0756 0.0499 0.0027 <.0001
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var61 var62 var63 var64 var79 0.38815 0.64833 0.65661 0.27214 anti-Cystatin A 0.1374 0.0066 0.0057 0.3079
16 16 16 16 var80 0.60344 0.78111 0.80276 0.46783 anti-Cystatin S 0.0133 0.0004 0.0002 0.0676
16 16 16 16 var81 0.60123 0.49617 0.58786 0.68834 Prostein 0.0297 0.0846 0.0346 0.0093
13 13 13 13 var82 0.58827 0.78204 0.77616 0.54320 Aquaporin 4 0.0344 0.0016 0.0018 0.0551
13 13 13 13 var83 0.78438 0.82710 0.88286 0.73909 Trypsin 0.0015 0.0005 <.0001 0.0039
13 13 13 13 var84 0.75388 0.64553 0.74148 0.72522 Osteonectin 0.0029 0.0172 0.0037 0.0050
13 13 13 13 var85 0.54583 0.72327 0.75261 0.48394 RAGE 0.0537 0.0052 0.0030 0.0938
13 13 13 13 var8S 0.44975 0.62512 0.61964 0.29243 PGRP-I Beeta 0.0805 0.0096 0.0105 0.2717
IS 16 16 16 var87 0.34650 0.51250 0.67057 0.42358 PGRP-S 0.2058 0.0508 0.0062 0.1156
15 15 15 15 var88 0.09980 0.02517 0.22992 0.31938
Gram positive bacteria 0.7234 0.9290 0.4097 0.2459
15 15 15 15 var89 0.78971 0.63146 0.86846 0.92S09
Troponin C Cardiac 0.0005 0.0116 <.0001 <.0001
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var65 var66 var67 var68 var79 0.55984 0.60025 0.15778 0.28408 anti-Cystatin A 0.0241 0.0140 0.5595 0.2863
16 16 16 16 var80 0.72023 0.74791 0.33688 0.48120 anti-Cystatin S 0.0017 0.0009 0.2020 0.0591
16 16 16 16 varδl 0.45312 0.53304 0.64166 0.44750 Prostein 0.1200 0.0607 0.0181 0.1252
13 13 13 13 var82 0.84130 0.74952 0.37159 0.37430 Aquaporin 4 0.0003 0.0032 0.2112 0.2077
13 13 13 13 var83 0.79524 0.81911 0.61402 0.70749 Trypsin 0.0012 0.0006 0.0256 0.0068
13 13 13 13 var84 0.69809 0.67479 0.59378 0.67924 Osteonectin 0.0080 0.0114 0.0324 0.0107
13 13 13 13 var85 0.64623 0.66844 0.39210 0.50449 RAGE 0.0170 0.0125 0.1851 0.0787
13 13 13 13 var86 0.73620 0.57573 0.30616 0.26966 PGRP-I Beeta 0.0011 0.0196 0.2488 0.3125
16 16 16 16 var87 0.61551 0.57814 0.32378 0.32604 PGRP-S 0.0146 0.0240 0.2391 0.2356
15 15 15 15 var88 0.09591 0.09622 0.18520 0.12252
Gram positive bacteria 0.7312 0.7330 0.5087 0.6636
15 15 15 15 var89 0.77124 0.79402 0.55294 0.68480
Troponin C Cardiac 0.0008 0.0004 0.0325 0.0049
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var69 var70 var71 var72 var79 0.08902 0.84617 0.86254 0.S7O08 anti-Cystatin A 0.7430 <.0001 <.0001 0.0045
16 16 16 16 var80 0.04308 0.94222 0.94450 0.82634 anti-Cystatin S 0.8741 <.0001 <.0001 <.0001
16 16 16 16 varδl -0.17828 0.41560 0.34463 0.61774 Prostein 0.5601 0.1578 0.2489 0.0245
13 13 13 13 var82 0.45195 0.77554 0.88482 0.6S781 Aquaporin 4 0.1210 0.0018 <.0001 0.0126
13 13 13 13 var83 -0.02502 0.85275 0.85897 0.92509 Trypsin 0.9353 0.0002 0.0002 <.0001
13 13 13 13 var84 -0.02988 0.65090 0.63550 0.80877 Osteonectin 0.9228 0.0160 0.0196 0.0008
13 13 13 13 var85 0.01338 0.91975 0.90123 0.83565 RAGE 0.9654 <.0001 <.0001 0.0004
13 13 13 13 var86 0.34950 0.86006 0.90804 0.53956 PGRP-I Beeta 0.1845 <.0001 <.0001 0.0310
16 16 16 16 var87 0.22719 0.83933 0.86254 0.59748 PGRP-S 0.4155 <.0001 <.0001 0.0187
15 15 15 15 var88 0.00424 0.23505 0.11790 0.31152
Gram positive bacteria 0.9880 0.3991 0.6756 0.2584
15 15 15 15 var89 0.02419 0.59769 0.60951 0.83985
Troponin C Cardiac 0.9318 0.0186 0.0159 <.0001
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var74 var75 var76 var77 var79 0.95065 0.87365 0.88261 0.73498 anti-Cystatin A <.0001 <.0001 <.0001 0.0012
16 16 16 16 var80 0.98876 0.96072 0.96496 0.78772 anti-Cystatin S <.0001 <.0001 <.0001 0.0003
16 16 16 16 varδl 0.27095 0.26561 0.27819 0.42677 Prostein 0.3706 0.3804 0.3574 0.1458 13 13 13 13 var82 0.80487 0.73352 0.73188 0.78437 Aquaporin 4 0.0009 0.0043 0.0045 0.0015
13 13 13 13 var83 0.81050 0.94321 0.93182 0.73055 Trypsin 0.0008 <.0001 <.0001 0.0046
13 13 13 13 var84 0.55723 0.79128 0.77244 0.55244 Osteonectin 0.0479 0.0013 0.0020 0.0503
13 13 13 13 var85 0.94751 0.99619 0.99832 0.81040 RAGE <.0001 <.0001 <.0001 0.0008
13 13 13 13 var86 0.86542 0.79197 0.79127 0.78131 PGRP-I Beeta <.0001 0.0003 0.0003 0.0004
IS 16 16 16 var87 0.79718 0.80613 0.81229 0.64579 PGRP-S 0.0004 0.0003 0.0002 0.0093
15 15 15 15 var88 0.13236 0.14755 0.15681 0.32006
Gram positive bacteria 0.6382 0.5997 0.5768 0.2448
15 15 15 15 var89 0.45863 0.671S5 0.65948 0.45934
Troponin C Cardiac 0.0855 0.0061 0.0075 0.0850
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var78 var79 var80 var81 var79 0.31464 1.00000 0.94281 0.15784 anti-Cystatin A 0.2353 <.0001 0.6066
16 16 16 13 var80 0.47320 0.94281 1.00000 0.30607 anti-Cystatin S 0.0641 <.0001 0.3091
16 16 16 13 var81 0.86681 0.15784 0.30607 1.00000 Prostein 0.0001 0.6066 0.3091
13 13 13 13 var82 0.37276 0.83045 0.82337 0.18530 Aquaporin 4 0.2097 0.0004 0.0005 0.5445
13 13 13 13 var83 0.61204 0.70372 0.87067 0.39375 Trypsin 0.0262 0.0073 0.0001 0.1831
13 13 13 13 var84 0.56517 0.39409 0.63937 0.35047 Osteonectin 0.0441 0.1827 0.0186 0.2404
13 13 13 13 var85 0.46888 0.88071 0.96645 0.25094 RAGE 0.1060 <.0001 <.0001 0.4083
13 13 13 13 var86 0.19213 0.80751 0.85976 -0.01466 PGRP-I Beeta 0.4759 0.0002 <.0001 0.9621
16 16 16 13 var87 0.21806 0.81081 0.82333 0.02490 PGRP-S 0.4350 0.0002 0.0002 0.9356
15 15 15 13 vara8 0.58223 0.12S25 0.16569 0.79652
Gram positive bacteria 0.0228 0.6539 0.5551 0.0011
15 15 15 13 var89 0.70499 0.34280 0.55916 0.50989
Troponin C Cardiac 0.0033 0.2110 0.0302 0.0751
15 15 15 13
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var82 var83 var84 var85 var79 0.83045 0.70372 0.39409 0.88071 anti-Cystatin A 0.0004 0.0073 0.1827 <.0001
13 13 13 13 var80 0.82337 0.87067 0.63937 0.96645 anti-Cystatin S 0.0005 0.0001 0.0186 <.0001
13 13 13 13 var81 0.18530 0.39375 0.35047 0.25094 Prostein 0.5445 0.1831 0.2404 0.4083
13 13 13 13 var82 1.00000 0.70084 0.44332 0.72579 Aguaporin 4 0.0076 0.1292 0.0050
13 13 13 13 var83 0.70084 1.00000 0.91879 0.92161 Trypsin 0.0076 <.0001 <.0001
13 13 13 13 var84 0.44332 0.91879 1.00000 0.76145 Osteonectin 0.1292 <.0001 0.0025
13 13 13 13 var85 0.72579 0.92161 0.76145 1.00000 RAGE 0.0050 <.0001 0.0025
13 13 13 13 var86 0.85694 0.70150 0.51983 0.82418 PGRP-I Beeta 0.0002 0.0075 0.0686 0.0005
13 13 13 13 var87 0.82189 0.76185 0.56874 0.86854 PGRP-S 0.0006 0.0025 0.0425 0.0001
13 13 13 13 var88 0.05410 0.18930 0.15744 0.17584
Gram positive bacteria 0.8607 0.5357 0.6075 0.5656
13 13 13 13 var89 0.55202 0.89433 0.92821 0.67189
Troponin C Cardiac 0.0505 <.0001 <.0001 0.0119
13 13 13 13
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var86 var87 var88 var89 var79 0.80751 0.81081 0.12625 0.34280 anti-Cystatin A 0.0002 0.0002 0.6539 0.2110
16 15 15 15 var80 0.85976 0.82333 0.16569 0.55916 anti-Cystatin S <.0001 0.0002 0.5551 0.0302
16 15 15 15 varδl 0.01466 0.02490 0.79652 0.50989 Prostein 0.9621 0.9356 0.0011 0.0751
13 13 13 13 var82 0.85694 0.82189 0.05410 0.55202 Aquaporin 4 0.0002 0.0006 0.8607 0.0505
13 13 13 13 var83 0.70150 0.76185 0.18930 0.89433 Trypsin 0.0075 0.0025 0.5357 <.0O01
13 13 13 13 var84 0.51983 0.56874 0.15744 0.92821 Osteonectin 0.0686 0.0425 0.6075 <.0O01
13 13 13 13 var85 0.82418 0.86854 0.17584 0.67189 RAGE 0.0005 0.0001 0.5656 0.0119
13 13 13 13 var86 1.00000 0.85133 -0.09081 0.39731 PGRP-I Beeta <.0001 0.7476 0.1425
16 15 15 15 var87 0.85133 1.00000 -0.03480 0.55209 PGRP-S <.0001 0.9020 0.0328
15 15 15 15 var88 0.09081 -0.03480 1.00000 0.19550
Gram positive bacteria 0.7476 0.9020 0.4850
15 15 IS 15 var89 0.39731 0.55209 0.19550 1.00000
Troponin C Cardiac 0.1425 0.0328 0.4850
15 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var90 var91 var92 var93 var79 0.18730 0.48182 0.43874 0.26314 anti-Cystatin A 0.5039 0.0690 0.0891 0.3248
15 15 16 16 var80 0.36078 0.69165 0.63886 0.45250 anti-Cystatin S 0.1865 0.0043 0.0077 0.0784
15 15 16 16 varβl 0.61938 0.58318 0.51539 0.6S757 Prostein 0.0240 0.0364 0.0715 0.0127
13 13 13 13 var82 0.48371 0.68835 0.55887 0.54800 Aquaporin 4 0.0940 0.0093 0.0471 0.0525
13 13 13 13 var83 0.62546 0.85621 0.93306 0.70198 Trypsin 0.0222 0.0002 <.0001 0.0075
13 13 13 13 var84 0.59980 0.80843 0.96761 0.67539 Osteonectin 0.0302 0.0008 <.0001 0.0113
13 13 13 13 var85 0.38074 0.66193 0.77204 0.44669 RAGE 0.1993 0.0137 0.0020 0.1260
13 13 13 13 var86 0.19127 0.56243 0.49232 0.28596 PGRP-I Beeta 0.4947 0.0291 0.0527 0.2830
15 15 16 16 var87 0.31719 0.54130 0.61012 0.40117 PGRP-S 0.2493 0.0372 0.0157 0.1383
15 15 15 15 var88 0.13040 0.18053 0.32210 0.25384
Gram positive bacteria 0.6432 0.5197 0.2417 0.3613
15 15 15 15 var89 0.83106 0.90625 0.96099 0.89939
Troponin C Cardiac 0.0001 <.0001 <.0001 <.0001
15 15 IS 15
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
Capture varl var2 var3 var90 0.39089 0.56636 0.92862 0.92091 Protein C 0.1497 0.0277 <.0001 <.0001
15 15 15 15 var91 0.75S47 0.84200 0.96143 0.91769
Macrophage Scavenger Receptor Type I 0.0011 <.0001 <.0001 <.0001
15 15 15 15 var92 0.75787 0.79912 0.82839 0.82862 anti-anti-Thrombin 0.0007" 0.0002 <.0001 <.0001
16 16 16 16 var93 0.49591 0.65320 0.97719 0.97947 Protein S 0.0508 0.0061 <-0001 <.0001
16 " 16 16 16
Pearson Correlation Coefficients Prob > I rI under HO : Rho=0 Number of Observations var4 var5 var6 var7 var90 0.93604 0.33069 0.41406 0.65986 Protein C <-0001 0.2286 0.1249 0.0074
15 15 15 15 var91 0.93836 0.44561 0.71031 0.44826
Macrophage Scavenger Receptor Type • I <.0001 0.0960 0.0030 0.0938
15 15 15 15 var92 0.82857 0.39380 0.57954 0.29249 anti-anti-Thrombin <.0001 0.1312 0.0186 0.2716
16 16 16 16 var93 0.98817 0.24174 0.50233 0.45812 Protein S <.0001 0.3671 0.0474 0.0743
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : RhO=O Number of Observations var8 var9 varlO varll var90 0.62900 0 .91107 0 .93905 -0. 01375 Protein C 0.0120 <.0001 <.0001 0.9612 15 15 15 15 var91 0.68505 0 .94536 0 .93775 0. 35659
Macrophage Scavenger Receptor Type I 0.0048 ■c.OOOl <.0001 0.1920 15 15 15 15 var92 0.53943 0 .89165 0 .83272 0. 40558 anti-anti-Thrombin 0.0310 <.0001 <.0001 0.1191 16 16 16 16 var93 0.54033 0.97842 0.989S3 0.04830 Protein S 0.0307 <.0001 <.0001 0.8590
IS 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations varl2 varl3 varl4 varlδ var90 0.92726 0.72997 0.40661 0.49882 Protein C <.0001 0.0020 0.132S 0.0584
15 15 15 15 var91 0.93549 0.93149 0.21533 0.39060
Macrophage Scavenger Receptor Type I <.0001 <.0001 0.4409 0.1500
15 15 15 15 var92 0.85985 0.88703 0.04224 0.20077 anti-anti-Thrombin <-0001 <.0001 0.8766 0.4559
16 16 16 16 var93 0.99001 0.81880 0.17569 0.30888 Protein S <-0001 0.0001 0.5151 0.2444
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : RhO=O Number of Observations varl6 varl7 varlβ varl9 var90 0.92471 0.90355 0.89337 0.96844 Protein C <.0001 <.0001 <-0001 <.0001
15 15 15 15 var91 0.86142 0.95866 0.93764 0.92907
Macrophage Scavenger Receptor Type I <.0001 <.0001 <.0001 <.0001
15 15 15 15 var92 0.78859 0.90290 0.86536 0.74990 anti-anti-Thrombin 0.0003 <.0001 <.0001 0.0008
16 16 16 16 var93 0.92812 0.95522 0.96613 0.98995 Protein <.0001 <.0001 <.0001 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : RhO=O Number of Observations var20 var21 var22 var23 var90 0.83621 0.46146 0.34787 0.59281 Protein C 0.0001 0.0834 0.2039 0.0199
15 15 15 15 var91 0.81715 0.75722 0.35555 0.55086
Macrophage Scavenger Receptor Type I 0.0002 0.0011 0.1934 0.0333
15 15 15 15 var92 0.75626 0.57468 0.21047 0.38958 anti-anti-Thrombin 0.0007 0.0199 0.4340 0.1358
16 16 16 16 var93 0.92874 0.54815 0.35786 0.44471 Protein S <.0001 0.0279 0.1735 0.0844
16 16 16 16
Pearson Correlation Coefficients .Prob > |r| under HO: Rho=0 Number of Observations var24 var25 var26 var27 var90 0.81509 0.92104 0.91406 0.92859 Protein C 0.0002 <.0001 <.0001 <.0001 15 15 15 15 var91 0.81524 0.93846 0.95348 0.92813
Macrophage Scavenger Receptor Type I 0.0002 <.0001 <.0001 <.0001
15 15 15 15 var92 0.69475 0.82751 0.82293 0.83603 anti-anti-Thrombin 0.0028 <.0001 <.0001 <.0001
15 16 16 16 var93 0.88083 0.96984 0.94976 0.98437 Protein S <-0001 <.0001 <.0001 <.0001
IS 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var28 var29 var30 var31 var90 0.10430 -0.05699 0.58160 0.49631 Protein C 0.7114 0.8401 0.0230 0.0599
15 15 15 15 var91 0.32557 0.20112 0.45893 0.43517
Macrophage Scavenger Receptor Type I 0.2364 0.4723 0.0853 0.1050
15 15 15 15 var92 0.18775 0.53809 0.30412 0.30531 anti-anti-Thrombin 0.4862 0.0315 0.2521 0.2502
16 16 16 16 var93 0.03568 -0.02353 0.38924 0.32536 Protein S 0.8956 0.9311 0.1362 0.2188
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var32 var33 var34 var35 var90 -0.03387 0.87849 0.86538 0.60007 Protein C 0.9046 <.0001 <.0001 0.0180
15 15 15 15 var91 0.03050 0.93609 0.94676 0.49530
Macrophage Scavenger Receptor Type I 0.9141 <.0001 <.0001 0.0605
15 15 15 15 var92 -0.18950 0.92807 0.72969 0.43441 anti-anti-Thrombin 0.4821 <.0001 0.0013 0.0927
16 16 16 16 var93 -0.12895 0.95257 0.94057 0.66225 Protein S 0.6341 <.0001 <.0001 0.0052
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var36 var37 var38 var39 var90 0.96074 0.85235 0.37928 0.91863 Protein C <.0001 <.0001 0.1632 <.0001
15 15 15 15 var91 0.92961 0.93565 0.42820 0.93554
Macrophage Scavenger Receptor Type I <.0001 <.0001 0.1113 <.0001
15 15 15 15 var92 0.76278 0.87988 0.33103 0.88277 anti-anti-Thrombin 0.0006 ■=.0001 0.2104 <.0001 16 16 16 16 var93 0.99433 0 .93529 0.42358 0.98343 Protein S <.0001 <.0001 0.1021 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var40 var41 var42 var43 var90 0.60794 0.68118 0.83233 0.89750 Protein C 0.0162 0.0052 0.0001 <.0001
15 15 15 15 var91 0.75267 0.89318 0.81371 0.84086
Macrophage Scavenger Receptor Type I 0.0012 <.0001 0.0002 <.0001
15 15 15 15 var92 0.83115 0.79922 0.77212 0.72378 anti-anti-Thrombin <.0001 0.0002 0.0005 0.0015
16 16 16 16 var93 0.68543 0.77315 0.89769 0.95311 Protein S 0.0034 0.0004 <.0001 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > I r I under HO : RhO=O Number of Observations var45 var46 var47 var48 var90 0.30716 0.38427 0.62082 0.18671 Protein C 0.2654 0.1573 0.0135 0.5052
15 15 15 15 var91 0.31161 0.24404 0.75377 0.51452
Macrophage Scavenger Receptor Type I 0.2582 0.3807 0.0012 0.0497
15 15 15 15 var92 0.24657 0.13869 0.61455 0.47584 anti-anti-Thrombin 0.3573 0.6085 0.0113 0.0625
16 16 16 16 var93 0.36594 0.14660 0.72193 0.27292 Protein S 0.1633 0.5880 0.0016 0.3065
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var49 var50 var51 var52 var90 0.27383 0.63228 0.83371 0.84705 Protein C 0.3234 0.0114 0.0001 <.0001
15 15 15 15 var91 0.66294 0.79051 0.80112 0.89373
Macrophage Scavenger Receptor Type I 0.0071 0.0005 0.0003 <.0001
15 15 15 15 var92 0.60380 0.96543 0.81250 0.86154 anti-anti-Thrombin 0.0133 <.0001 0.0001 <.0001
16 16 16 16 var93 0.38026 0.70399 0.84266 0.93617 Protein S 0.1463 0.0023 <.0001 <.0001
16 16 16 16 Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var53 var54 var55 var56 var90 0.93877 -0.09663 0.46724 0.69417 Protein C <.0001 0.7319 0.0791 0.0041
15 15 15 15 var91 0.82827 0.12604 0.62452 0.81900
Macrophage Scavenger Receptor Type I 0.0001 0.6544 0.0128 0.0002
15 15 15 15 var92 0.70344 0.54381 0.71998 0.97314 anti-anti-Thrombin 0.0024 0.0294 0.0017 <.0001
IS 16 16 16 var93 0.92101 0.00237 0.53740 0.76502 Protein S <.0001 0.9931 0.0318 0.0006
IS 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var57 var58 var59 var60 var90 0.40616 0.40490 0.62380 0.50800 Protein C 0.1330 0.1344 0.0130 0.0532
15 15 15 15 var91 0.71517 0.65629 0.88281 0.68568
Macrophage Scavenger Receptor Type I 0.0027 0.0079 <.0001 0.0048
15 15 15 15 var92 0.47773 0.60988 0.67717 0.93325 anti-anti-Thrombin 0.0613 0.0121 0.0040 <.0001
16 16 16 16 var93 0.49011 0.42569 0.69832 0.57932 Protein S 0.0539 0.1002 0.0026 0.0187
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var61 var62 var63 var64 var90 0.80517 0.64852 0.81434 0.92181 Protein C 0.0003 0.0089 0.0002 <.0001
15 15 15 15 var91 0.94055 0.84910 0.95644 0.90994
Macrophage Scavenger Receptor Type I <.0001 <.0001 <.0001 <.0001
15 15 15 15 var92 0.68708 0.55244 0.82220 0.83509 anti-anti-Thrombin 0.0033 0.0265 <.0001 <.0001
16 16 16 16 var93 0.85432 0.69887 0.89091 0.99289 Protein S <.0001 0.0026 <.0001 <.0001
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var65 var66 var67 var68 var90 0.72665 0.80575 0.50696 0.53034 Protein C 0.0022 0.0003 0.0538 0.0420
15 15 15 15 var91 0.93190 0.93380 0.55416 0.69375
Macrophage Scavenger Receptor Type I <.0001 <.0001 0.0321 0.0041
IS 15 15 15 var92 0.74705 0.69840 0.53S38 0.60305 anti-anti-Thrombin 0.0009 0.0026 0.0322 0.0134
16 16 16 16 var93 0.79661 0.86555 0.61175 0.64438 Protein S 0.0002 <.0001 0.0118 0.0071
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var69 var70 var71 var72 var90 -0.01252 0.41728 0.46588 0.70872 Protein C 0.9647 0.1217 0.0801 0.0031
15 15 15 15 var91 0.09838 0.71321 0.75622 0.89462
Macrophage Scavenger Receptor Type I 0.7272 0.0028 0.0011 <.0001
15 IS 15 15 var92 0.08803 0.67887 0.66157 0.83460 anti-anti-Thrombin 0.7458 0.0038 0.0053 <.0001
16 16 16 16 var93 0.03360 0.52584 0.55874 0.78943 Protein S 0.9017 0.0364 0.0245 0.0003
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var74 var75 var76 var77 var90 0.28355 0.38415 0.38121 0.33650 Protein C 0.3058 0.1575 0.1609 0.2201
15 15 15 15 var91 0.62473 0.70883 0.70037 0.60770
Macrophage Scavenger Receptor Type I 0.0128 0.0031 0.0036 0.0163
15 15 15 15 var92 0.54461 0.76073 0.75113 0.60732 anti-anti-Thrombin 0.0292 0.0006 0.0008 0.0126
16 16 16 16 var93 0.36999 0.47032 0.46559 0.38812 Protein 0.1584 0.0660 0.0691 0.1374
16 16 16 16
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations var78 var79 var80 var81 var90 0.80854 0.18730 0.36078 0.61938 Protein C 0.0003 0.5039 0.1865 0.0240
15 15 15 13 var91 0.76806 0.48182 0.69165 0.58318
Macrophage Scavenger Receptor Type I 0.0008 0.0690 0.0043 0.0364
15 15 15 13 var92 0.70411 0.43874 0.63886 0.51539 anti-anti-Thrombin 0.0023 0.0891 0.0077 0.0715
16 16 16 13 var93 0.79565 0.26314 0.45250 0.66757 Protein S 0.0002 0.3248 0.0784 0.0127 16 16 \6 13
Pearson Correlation Coefficients fit) Prob > |r| under HO: Rho=0 Number of Observations var82 var83 var84 var85 var90 0.48371 0.6254S 0.59980 0.38074 Protein C 0.0940 0.0222 0.0302 0.1993
13 13 13 13 var91 0.68835 0.85S21 0.80843 0.66193
Macrophage Scavenger Receptor Type I 0.0093 0.0002 0.0008 0.0137
13 13 13 13 var92 0.55887 0.93306 0.96761 0.77204 anti-anti-Throinbin 0.0471 <.0001 <.0001 0.0020
13 13 13 13 var93 0.54800 0.70198 0.67539 0.44669 Protein S 0.0525 0.0075 0.0113 0.1260
13 13 13 13
Pearson Correlation Coefficients Prob > I rI under HO : RhO=O Number of Observations var86 var87 var88 var89 var90 0.19127 0.31719 0.13040 0.83106 Protein C 0.4947 0.2493 0.6432 0.0001
15 15 15 15 var91 0.56243 0.54130 0.18053 0.90625
Macrophage Scavenger Receptor Type I 0.0291 0.0372 0.5197 <.0001
15 15 15 15 var92 0.49232 0.61012 0.32210 0.96099 anti-anti-Thrombin 0.0527 0.0157 0.2417 <.O0Ol
16 15 15 15 var93 0.28596 0.40117 0.25384 0.89939 Protein S 0.2830 0.1383 0.3613 <.0001
16 15 15 15
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations var90 var91 var92 var93 var90 1.00000 0.86141 0.69682 0.95200 Protein C <.0001 0.0039 <.0001
15 15 15 15 var91 0.86141 1.00000 0.84966 0.91518
Macrophage Scavenger Receptor Type I <.0001 <.0001 <.O0Ol
15 15 15 15 var92 0.69682 0.84966 1.00000 0.78758 anti-anti-Thrombin 0.0039 <.0001 0.0003
15 15 16 16 var93 0.95200 0.91518 0.78758 1.00000 Protein S <.0001 <.0001 0.0003
15 15 16 16 Table 12. Marker Versus Capture Data
Statistical Analysis: Comparisons of Disease for a given Biomarker
Variable Label
Cap Capture
MHCI MHC-I
MaSR Macrophage scavenger receptor
CysA Cystatin A
Kalβ Kallikrein 6
AIpS Alpha synuclein
Onctin Osteonectin
Olcin Osteocalcin
TroC Troponin C
AbT Abeam Transglutaminase 2
PGRP PGRP-I Beeta
PSA PSA
Lab Labvision Tgase 2
Aqua Aquaporin-4
Capture Time DATA: Summary table of Cap by Disease
Figure imgf000379_0001
Capture Time DATA: Summary table of MHCI by Disease
Figure imgf000379_0002
Capture Time DATA: Summary table of MaSR by Disease
Macrophage scavenger receptor
I I I I |Medi-| I Mean I Min I Max I Ql I an Q3
I Disease
II - . _-
Aortic 110.00 I 26.64111.43 I 59.90114.92) 20.97 37.38
Arthriti 110.00 I 215.2 j 33.89 I 288.31183.9 | 249.5 | 269.6
Ostitis 110.001158.9112.40 I 320.9119.771143.91269.2 Endoaden 110.00 I 41.54 J 11.78 I 76.91139.52 I 44.67 I 48.22
KidSton 110.00 I 38.40 I 22.02 I 45.21136.36 I 40.20 I 43.42 J I I Parkinso 110.00 ) 20.94117.26 I 24.60 I 20.46 I 21.07 I 21.50
Prostate I 9.00112.90110.21116.39110.65111.96115.61 Prostati 110.00 I 25.42113.18 I 40.89 J 15.61123.95 I 34.32
Capture Time DATA: Summary table of CysA by Disease
Cystatin A
I I I I |Medi-| N ] Mean | Min | Max | Ql | an | Q3
Disease
-- -
Aortic 10.00 22.33 20.03 25.03 20.98 21.76 24.00
Arthriti 10.00 8.72 2.33 13.35 3.43 12.09 12.22
Ostitis 10.00 8.63 4.26 13.18 4.45 8.19|l2.92
Endoaden 10.00|21.58 2.97 29.38 23.14 24.86 26.82
KidSton 10.00 3.96 1.58 7.00 2.42 3.48 5.09
Parkinso |l0.00 3.44 2.97 3.90 3.25 3.34 3.62
Prostate 10.00 4.49 0.19 13.70 0.47 0.93 8.43
Prostati |l0.00 25.47|22.36 31.76 23.91 24.08|26.48
Capture Time DATA: Summary table of Kal6 by Disease
Kallikrein 6
I Medi¬
N Mean Min I Max I Ql an Q3
_ __ _ _ . Disease I I I Aortic 10.00 0.05 II o.oo I| 0.28 I| 0.00 0.00 0.00 -_ - Arthriti 10.00 1.27| o.oo| 2.42| 0.00 1.81 2.23
_ Ostitis 10.00 1.65 I 0.5S I 3.07| 0.75 1.16 2.79
_ __ --
Endoaden 10.00 1.79| 0.09 I 2.88 J 0.93 1.95 2.88
KidSton 10.00 0.2l| o.oo| 0.47| 0.09 0.19 0.28 __ _ j Parkinso 110.001 2.60| 2.42| 3.43| 2.42| 2.5l| 2.60 I Prostate I XO .00 I 0.25| 0.09 I 0.56| 0.19 | 0.19| 0.37 j
I I
I Prostati I XO .00 I 0.82| 0.09 I 1.58| 0.56 | 0.79 | 1.12J
Capture Time DATA: Summary table of Alps by Disease
Alpha synuclein
I I I I lMedi-1 N I Mean | Min | Max | Ql j an | Q3
Disease Aortic J 10.00 j 14.27 J 12. S6115.78 j 13.53 14.31115.09 j
Arthriti llO.OO 37.24 23.57 44.40 35.68 I 37.30 I 42.54 Ostitis 110.00 I 26.04 J 5.73 I 34.49 I 22.54 I 30.91133.21
Endoaden 110.00 J 36.71110.91146.66 I 37.55 I 42.63 I 43.60 KidSton 110.00115.75 I 9.85 I 21.67 I 13.01115.52118.64
Parkinso 110.00 I 24.57 I 23.74 I 28.19 I 23.91124.26 I 24.43 Prostate |10.00| 5.74| 0.00|10.2l| 2.42| 6.90 | 9.15 Prostati 110.00 I 35.10 I 22.71147.94 I 30.91 J 32.87 J 42.90
Capture Time DATA: Summary table of Onctin by Disease
Osteonectin
|Medi-
N Mean Min Max Ql an Q3
Disease __ Aortic 110.00 0.89 0.72 1.18 0.72 0.81 1.09
Arthriti 10.00 1.72 0.62 3.13 0.81 1.74 2.20
Ostitis 10.00 1.09 0.25 3.03| 0.44 0.58 1.46
Endoaden 10.00 1.11 0.34 2.39 0.81 1.04 1.46
KidSton 10.00 0.32 0.25 0.53 0.25 0.25 0.44
Parkinso 10.00 2.89 2.20 4.05| 2.48 2.53 3.77
Prostate 10.00 0.44 0.25 0.72 0.34 0.39 0.53
Prostati 10.00 0.97 0.53 1.65 0.81 0.95 1.09
Capture Time DATA: Summary table of Olcin by Disease
Osteocalcin
I I I I |Medi-| N I Mean | Min | Max | Ql | an | Q3
Disease
Aortic 10 .00 4 .35 3 .52 6 .04 3 .73 4- 10 I 4 .78
Arthriti 10 .oo|io .71 1 .38 16 .76 6 .14 12. 37 16 .29
Cstitis 10 .00 10 .12 3 .63 19 .84 4 .05 ' 51118 .77 ] j 10.001 2.7l| 0.00| 3.84| 2.35| 3.2l| 3.63 IEndoaden
I KidSton 110.00 I 0.14 I 0.00 I 0.4l| 0.00| 0.19| 0.19
I IP-a—rkinso 110.00 I 2.57| 1.59| 3.2θ| 1.811 2.82 | 2.98
I
I Prostate 110.001 0.00] 0.00| O.OO] 0.00| 0.00| O.OO
_. _ _-
Prostati 110.001 2. ll| 1.17| 3.42| 1.4δ| 1.87| 2.78
Capture Time DATA: Summary table of TroC by Disease
Figure imgf000382_0001
Capture Time DATA: Summary table of AbT by Disease 10
Abeam Transglutaminase 2
I 1 I I |Medi-| N ]Mean | Min | Max | Ql | an | Q3
Disease Aortic jlθ.00 3.81 j 0.65|l6.74| 1.2l| 1.4θj 1.68
Arthriti 110.001 2.56| 1.30| 4.17] 1.4θ| 3.021 3.16 Cstitis 110.00 I 0.50 I 0.09| 1.03| 0.09| 0.42] 0.84
Endoaden J 10.00 ] 0.34] O.OO] 1.12| 0.091 0.141 0.47 KidSton 110.00 I 0.05 I 0.0θ| 0.28 I 0.00| 0.00| 0.09 j
Parkinso 110.001 3.07| 2.70| 4.17] 2.79] 2.97] 3.16 Prostate 110.001 0.07] O.OO] 0.281 O.Oθ| 0.09| 0.09 Prostati 110.00 ] 0.5l| 0.00| 1.77| 0.09| 0.14| 0.75
Capture Time DATA: Summary table of PGRP by Disease 11
PGRP-I Beeta
I I I I |Medi-| N IMean | Min | Max | Ql | an | Q3
Disease Aortic 110.00 j 308.21127.6 I 640.01164.8 j 195.9 441.2
Figure imgf000383_0001
Capture Time DATA: Summary table of PSA by Disease 12
PSA
I I I I |Medi-|
I Mean I Min 1 Max | Ql I an Q3
Disease Aortic jl0.00|41.65 20.41 49.16 j 39.69 j 43.12 | 46.17
Arthriti 110.00 I 24.62 I 4.45 I 41.01112.00 I 25.67 I 38.81 Ostitis 110.00 I 24.02111.69 I 38.02112.08 I 21.46 I 36.69 I I
Endoaden 110.00 I 34.50 I 0.04 I 46.26 J 40.66 I 42.10 I 43.55 I KidSton 110.00 I 4.34| 3.27| 4.96 | 4.12 | 4.33| 4.75| __ι
I
Parkinso 110.00112.41112.00113.82112.10 I 12.14112.58 I Prostate 110.00 I 0.25 J 0.04| 0.47| 0.04 | 0.2S | 0.47 Prostati 10.00 I 40.42 I 35.13 I 45.14 I 38.46 J 40.77 I 43.34
Capture Time DATA: Summary table of Lab by Disease 13
Labvision Tgase 2
I I I I |Medi-| N I Mean | Min | Max | Ql | an | Q3
Disease
Aortic 110.00 I 1.04J 0.80 j 1.45) 0.80 1.02 j 1.23
Arthriti 110.001 0.441 0.04 I 0.801 0.261 0.471 0.58
Cstitis I XO .001 9.10| 0.22|25.64| 0.44| 5.74|14.53
Endoaden 110.00 I 3.28 I O.OOl 8.65| 0.871 2.70 I 4.92
I KidSton I 9.00| 2.651 0.00|l4.34| 0.221 0.44| 2.38
Parkinso ] 10.00 I 0.46| 0.3S I 0.69| 0.36 | 0.42J 0.58
Prostate 110.001 1.121 0.00| 3.66| O.Oθ| 0.33| 2.81 Prostati 110.001 0.461 O.OOl 1.30| 0.151 0.401 0.65
Capture Time DATA: Summary table of Aqua by Disease 14
Figure imgf000383_0002
I N I Mean | Min | Max | Ql | an | Q3 |
Disease I I I I I '"] ϊ" Aortic I 110.00II 344.611119.8II 640.0I1129.6II 203.2II 636.7
|Arthriti 110.00 I 506.9 I 87.57 I 640.0 I 434.0 I 640.0 I 640.0 I Ostitis I 9.00]285.9| 7.83|640.0|91.18|l46.4|640.0
I Endoaden I 8.00|480.0| 0.00|640.0|320.0|640.0|640.0
II
I KidSton 110.00 J 54.24 I 33.69 I 65.62 I 44.02 I 57.34 I 62.22
Parkinso 110 .00 I 88.73 I 83 .44 I 96 .42 I 84 .111 88.01191.77 j Prostate I XO . 00 1 0 . 49 | 0 . 00 | 1 . 32 | O . Oθ | 0 . 47 | 0 . 81
Prostati 1 10 . 00 I 413 . 8 I 107 . 0 | 640 . 0 1 180 . 7 | 486 .4 | 640 . 0
Capture Time DATA: Summary table of Aqua by Disease Disease=Aortic
The CORR Procedure
14 Variables : Cap MHCI MaSR CysA KaI 6 AIpS Onctin Olcin TroC
AbT PGRP PSA Lab Aqua
Simple Statistics
Variable N Mean Std Dev Sum Minimum Maximum
Cap 10 193.35880 57.46218 1934 126.40200 284.26200
MHCI 10 316.51770 178.59011 3165 129.75100 640.00000
MaSR 10 26.63810 15.80507 266.38100 11.43400 59.90200
CysA 10 22.33410 1.87045 223.34100 20.02900 25.02800
KaI 6 10 0.04670 0.10086 0.46700 0 0.28000
AIpS 10 14.27370 1.00644 142.73700 12.65700 15.78400
Onctin 10 0.89170 0.18831 8.91700 0.71500 1.18000
Olcin 10 4.34790 0.82234 43.47900 3.51500 6.03500
TroC 10 0.23310 0.22508 2.33100 0 0.55900
AbT 10 3.81430 5.54836 38.14300 0.65300 16.73700
PGRP 10 308.20130 194.39359 3082 127.58400 640.00000
PSA 10 41.64730 8.06573 416.47300 20.41200 49.15800
Lab 10 1.03670 0.22155 10.36700 0.79800 1.44800
Aqua 10 344.57210 250.47222 3446 119.83200 640.00000
Capture Time DATA: Summary table of Aqua by Disease Disease=Aortic
The CORR Procedure Pearson Correlation Coefficients 10
Prob > |r| under HO: RhO=O
Cap MHCI CysA KaI6
Cap 1.00000 0.77937 0.91001 0.88507 0.28388 Capture 0.0079 0.0003 0.0007 0.4267
MHCI 0.77937 1.00000 0.74390 0.60917 0.45890 MHC-I 0.0079 0.0136 0.0616 0.1822
MaSR 0.91001 0.74390 1.00000 0.91742 0.38707 Macrophage scavenger receptor 0.0003 0.0136 0.0002 0.2692
CysA 0.88507 0.60917 0.91742 1.00000 0.08807 Cystatin A 0.0007 0.0616 0.0002 0.8088
Kal6 0.28388 0.45890 0.38707 0.08807 1.00000 Kallikrein 6 0.4267 0.1822 0.2692 0.8088
AIpS 0.61478 0.40868 0.57675 0.63386 -0.00844 Alpha synuclein 0.0586 0.2410 0.0809 0.0491 0.9815
Onctin 0.63957 0.81997 0.69384 0.48709 0.78761 Osteonectin 0.0464 0.0037 0.0260 0.1S33 0.0068
Olcin 0.81900 0.68190 0.95162 0.80644 0.58545 Osteocalcin 0.0038 0.0299 ■=.0001 0.0048 0.0754
TroC 0.06893 0.29550 0.22927 -0.02898 0.57466 Troponin C 0.8499 0.4071 0.5240 0.9367 0.0823
AbT -0.02341 0.24309 0.05379 0.08844 -0.21895 Abeam Transglutaminase 2 0 94SS 0 4986 0 8827 0 8080 0 5434
PGRP 0 91946 0 79173 0 95391 0 92665 0 20306
PGRP 1 Beeta 0 0002 0 0063 < 0001 0 0001 0 5737
PSA 0 S3188 0 40037 0 56966 0 58485 0 23093
PSA 0 1136 0 2516 0 0856 0 0758 0 5209
Lab 0 77213 0 66404 0 89974 0 72932 0 50397
Labvision Tgase 2 0 0089 0 0363 0 0004 0 0167 0 1375
Aqua 0 92857 0 65337 0 90041 0 94063 0 10228
Aquaporin-4 0 0001 0 0405 0 0004 < 0001 0 7786
Capture Time DATA Summary table of Aqua by Disease 1
The CORR Procedure
Pearson Correlation Coefficients, N = 10
Prob > | r| under HO Rho=0
AIpS Onctm 01cm TroC AbT
Cap 0 61478 0 63957 0 81900 0 06893 -0 02341
Capture 0 0586 0 0464 0 0038 0 8499 0 9488
MHCI 0 40868 0 81997 0 68190 0 29550 0 24309
MHC-I 0 2410 0 0037 0 0299 0 4071 0 4986
MaSR 0 57675 0 69384 0 95162 0 22927 0 05379
Macrophage scavenger receptor 0 0809 0 0260 < 0001 0 5240 0 8827
CysA 0 63386 0 48709 0 80644 -0 02898 0 08844
Cystatin A 0 0491 0 1533 0 0048 0 9367 0 8080
Kal6 -0 00844 0 78761 0 58545 0 57466 -0 21895
Kallikrem 6 0 9815 0 0068 0 0754 0 0823 0 5434
AIpS 1 00000 0 25886 0 50408 -0 19435 -0 10261
Alpha synuclem 0 4702 0 1374 0 5906 0 7779
Onetin 0 25886 1 00000 0 80654 0 66999 0 15630
Osteonectin 0 4702 0 0048 0 0340 0 6663
01cm 0 50408 0 80654 1 00000 0 44482 0 00008
Osteocalcin 0 1374 0 0048 0 1977 0 9998
TroC -0 19435 0 66999 0 44482 1 00000 0 39567
Troponin C 0 5906 0 0340 0 1977 0 2577
AbT -0 10261 0 15630 0 00008 0 39567 1 00000
Abeam TransglutammaE >e 2 0 7779 0 6663 0 9998 0 2577
PGRP 0 61786 0 65572 0 86128 0 21545 0 25927
PGRP-I Beeta 0 0570 0 0395 0 0014 0 5500 0 4695
PSA 0 55543 0 51852 0 63095 0 32187 0 19342
PSA 0 0955 0 1247 0 0505 0 3644 0 5924
Lab 0 40713 0 78408 0 94621 0 56328 0 09840
Labvision Tgase 2 0 2429 0 0073 < 0001 0 0900 0 7868
Aqua 0 61658 0 55396 0 80621 0 14018 0 21783
Aquaporin-4 0 0576 0 0966 0 0048 0 6993 0 5455
Capture Time DATA Summary table of Aqua by Disease 18
The CORR Procedure
Pearson Correlation Coefficients, N = 10 Prob > |r| under HO RhO=O
PGRP PSA Lab Aqua
Cap 0 91946 0 53188 0 77213 0 92857 Capture 0 0002 0 1136 0 0089 0 0001
MHCI 0 79173 0 40037 0 66404 0 65337 MHC-I 0 0063 0 2516 0 0363 0 0405
MaSR 0 95391 0 56966 0 89974 0 90041 Macrophage scavenger receptor < 0001 0 0856 0 0004 0 0004
CysA 0 92665 0 58485 0 72932 0 94063 Cystatm A 0 0001 0 0758 0 0167 < 0001
Kal6 0 20306 0 23093 0 50397 0 10228 Kallikrem 6 0.5737 0 5209 0.1375 0.7786
AIpS 0.61786 0.55543 0.40713 0.61S58
Alpha synuclem 0.0570 0 0955 0.2429 0 0576
Onctin 0.65572 0.51852 0.78408 0.55396 Osteonectin 0.0395 0 1247 0.0073 0.0966
Olcin 0.86128 0 63095 0 94621 0.80621 Osteocalcin 0.0014 0 0505 <.0001 0.0048
TroC 0.21545 0.32137 0 56328 0.14018 Troponin C 0.5500 0.3644 0.0900 0.6993
AbT 0.25927 0.19342 0.09840 0.21783
Abeam Transglutaminase 2 0.4695 0.5924 0.7868 0.5455
PGRP 0.56921 0.85486 0.95877
PGRP-I Beeta 0.0859 0.0016 <.0001
PSA 0.56921 0.47426 0.59432 PSA 0.0859 0.1661 0.0700
Lab 0.85486 0.47426 1.00000 0.79552
Labvision Tgase 2 0.0016 0.1661 0.0059
Aqua 0.95877 0.59432 0.79552 1.00000 Aquaporm-4 <.0001 0.0700 0 0059
Capture Time DATA: Summary table of Aqua by Disease 19
-- Disease=Arthriti
The CORR Procedure
14 Variables: Cap MHCI MaSR CysA Kal6 AIpS Onctin Olcin TroC AbT PGRP PSA Lab Aqua
Simple Statistics
Variable N Mean Std Dev Sum Minimum Maximum
Cap 10 273.44670 105.74732 2734 99.29800 376.80300
MHCI 10 433.06410 268.22001 4331 61.32000 640.00000
MaSR 10 215.18610 78.01752 2152 33.89000 288.26300
CysA 10 8.71720 4.81053 87.17200 2.32500 13.35300
KaI6 10 1 26510 1.10598 12.65100 0 2.41800
AIpS 10 37.23840 6.17773 372.38400 23.56900 44.40200
Onctin 10 1.71790 0.88313 17.17900 0.62200 3.12700
01cm 10 10.71290 6.18346 107.12900 1.37600 16.76200
TroC 10 0.96820 0.84432 9.68200 0 1.86100
AbT 10 2.56350 1.10726 25.63500 1 30400 4.17000
PGRP 10 449.03710 249.41922 4490 59.38500 640.00000
PSA 10 24.61580 15.83829 246.15800 4 44900 41.00700
Lab 10 0.43950 0.26663 4.39500 0.03600 0.79800
Aqua 10 506.91800 200.50050 5069 87.57400 640.00000
Simple Statistics Variable Label
Cap Capture
MHCI MHC-I
MaSR Macrophage scavenger receptor
CysA Cystatm A
Kal6 Kallikrein 6
Alps Alpha synuclem
Onctm Osteonectin
01cm Osteocalcin
TroC Troponin C
AbT Abeam Transglutaminase 2
PGRP PGRP-I Beeta
PSA PSA
Lab Labvision Tgase 2
Aqua Aquaporm-4
Capture Time DATA: Summary table of Aqua by Disease 20 Disease=Arthriti
The CORR Procedure
Pearson Correlation Coefficients, N = 10 Prob > |r| under HO: RhO=O
Cap MHCI MaSR CysA KaI6
Cap 1.00000 0.98634 0.91859 0.98662 0.9S744 Capture <.0001 0.0002 <.0001 <.0001 MHCI 0.98634 1.00000 0.87162 0.99673 0.98057 MHC-I <-0001 0.0010 <.0001 <-0001
MaSR 0.91859 0.87162 1.00000 0.86645 0.82802
Macrophage scavenger receptor 0.0002 0.0010 0.0012 0.0031
CysA 0.98662 0.99673 0.86645 1.00000 0.99016 Cystatin A <.0001 <.0001 0.0012 <.0001
Kal6 0.96744 0.98057 0.82802 0.99016 1.00000 Kallikrein 6 <.0001 <.0001 0.0031 <.0001
AIpS 0.00025 -0.11970 0.32917 -0.13513 -0.18165
Alpha synuclein 0.9995 0.7419 0.3530 0.7097 0.6155
Onctin 0.81068 0.81629 0.67695 0.81476 0.84096 Osteonectin 0.0044 0.0040 0.0316 0.0041 0.0023
Olcin 0.89121 0.91872 0.87741 0.91072 0.87232 Osteocalcin 0.0005 0.0002 0.0008 0.0002 0.0010
TroC 0.97069 0.98302 0.81928 0.98987 0.99690 Troponin C <.0001 <-0001 0.0037 <.0001 <.0001
AbT 0.95182 0.94049 0.81726 0.96321 0.97608
Abeam Transglutaminase 2 <.0001 <.0001 0.0039 <.0001 <.0001
PGRP 0.99210 0.99654 0.90516 0.99146 0.97038
PGRP-I Beeta <.0001 <.0001 0.0003 <.0001 •=.0001
PSA 0.72508 0.77606 0.73763 0.76786 0.71640 PSA 0.0177 0.0083 0.0149 0.0095 0.0198
Lab 0.71789 0.77911 0.72889 0.76173 0.73877
Labvision Tgase 2 0.0194 0.0079 0.0168 0.0105 0.0147
Aqua 0.92572 0.89410 0.96586 0.88054 0.84360 Aquaporin-4 0.0001 0.0005 ■=.0001 0.0008 0.0022
Capture Time DATA: Summary table of Aqua by Disease Disease=Arthriti
The CORR Procedure
Pearson Correlation Coefficients, N = 10 Prob > |r| under HO: Rho=0
AIpS Onctin Olcin TroC AbT
Cap -0.00025 0.81068 0.89121 0.97069 0.95182 Capture 0.9995 0.0044 0.0005 <.0001 <.0001
MHCI -0.11970 0.81629 0.91872 0.98302 0.94049 MHC-I 0.7419 0.0040 0.0002 <.0001 <.0001
MaSR 0.32917 0.67695 0.87741 0.81928 0.81726
Macrophage scavenger receptor 0.3530 0.0316 0.0008 0.0037 0.0039
CysA -0.13513 0.81476 0.91072 0.98987 0.96321 Cyatatin A 0.7097 0.0041 0.0002 <.0001 <.0001
KaI6 -0.18165 0.84096 0.87232 0.99690 0.97608 Kallikrein 6 0.6155 0.0023 0.0010 <.0001 <.0001
Alps 1.00000 -0.09078 -0.04573 -0.17474 -0.13800
Alpha synuclein 0.8031 0.9002 0.6292 0.7038
Onctin -0.09078 1.00000 0.60931 0.84182 0.80392 Osteonectin 0.8031 0.0615 0.0023 0.0051
Olcin -0.04573 0.60931 1.00000 0.85904 0.81453 Osteocalcin 0.9002 0.0615 0.0015 0.0041
TroC -0.17474 0.84182 0.85904 1.00000 0.97251 Troponin C 0.6292 0.0023 0.0015 <.0001
AbT -0.13800 0.80392 0.81453 0.97251 1.00000
Abeam Transglutaminase 2 0.7038 0.0051 0.0041 <.0001
PGRP -0.04653 0.80340 0.92675 0.97286 0.93163
PGRP-I Beeta 0.8984 0.0051 0.0001 <.oooi <.0001
PSA -0.08985 0.40653 0.94475 0.69442 0.64698 PSA 0.8050 0.2437 <.0001 0.0259 0.0432
Lab -0.11203 0.52083 0.92626 0.71582 0.62879
Labvision Tgase 2 0.7580 0.1227 0.0001 0.0199 0.0515 Aqua 0 24S81 0 S6186 0 89157 0 84571 0 81053 Aquaporm 4 0 4936 0 0371 0 0005 0 0020 0 0045
Capture Time DATA Summary table of Aqua by Disease 22 Disease=Arthπti
The CORR Procedure
Pearson Correlation Coefficients N Prob > |r| under HO RhO=O
PGRP PSA Lab Aqua
Cap 0 99210 0 72508 0 71789 0 92572 Capture < 0001 0 0177 0 0194 0 0001
MHCI 0 99654 0 77606 0 77911 0 89410 MHC-I < 0001 0 0083 0 0079 0 0005
MaSR 0 90516 0 73763 0 72889 0 96586
Macrophage scavenger receptor 0 0003 0 0149 0 0168 < 0001
CysA 0 99146 0 76786 0 76173 0 88054 Cystatm A < 0001 0 0095 0 0105 0 0008
KaIS 0 97038 0 71640 0 73877 0 84360 Kallikrem 6 < 0001 0 0198 0 0147 0 0022
AIpS -0 04653 -0 08985 -0 11203 0 24581
Alpha synuclem 0 8984 0 8050 0 7580 0 4936
Onctin 0 80340 0 40653 0 52083 0 65186 Osteonectin 0 0051 0 2437 0 1227 0 0371
01cm 0 92675 0 94475 0 9262S 0 89157 Osteocalcin 0 0001 < 0001 0 0001 0 0005
TroC 0 97286 0 69442 0 71582 0 84571 Troponin C < 0001 0 0259 0 0199 0 0020
AbT 0 93163 0 64698 0 62879 0 81053
Abeam Transglutaminase 2 < 0001 0 0432 0 0515 0 0045
PGRP 1 00000 0 77887 0 78734 0 92678
PGRP-I Beeta 0 0079 0 0069 0 0001
PSA 0 77887 1 00000 0 90065 0 72263 PSA 0 0079 0 0004 0 0182
Lab 0 78734 0 90065 1 00000 0 78082
Labvision Tgase 2 0 0069 0 0004 0 0077
Aqua 0 92678 0 72263 0 78082 1 00000 Aquaporin-4 0 0001 0 0182 0 0077
Capture Time DATA Summary table of Aqua by Disease 23
- Disease=Cstitis -- The CORR Procedure
14 Variables Cap MHCI MaSR CysA KaIS AIpS Onctm 01cm AbT PGRP PSA Lab Aqua
Simple Statistics
Variable N Mean Std Dev Sum Minimum Maximum
Cap 10 256 00540 123 82985 2560 106 70700 414 54800
MHCI 10 329 35080 271 41116 3294 42 20500 640 00000
MaSR 10 158 90600 116 541S8 1589 12 39500 320 93000
CysA 10 8 63020 4 04581 86 30200 4 26200 13 17900
KaI6 10 1 64630 0 99759 16 46300 0 55900 3 06500
AIpS 10 26 03880 10 98058 260 38800 5 72600 34 48500
Onctm 10 1 085S0 0 96504 10 85600 0 24900 3 03400
01cm 10 10 12300 6 95485 101 23000 3 63000 19 84400
TroC 10 0 71S90 0 85S40 7 16900 0 1 95400
AbT 10 0 50330 0 37848 5 03300 0 09300 1 02500
PGRP 10 190 69570 123 63813 1907 41 94700 408 02100
PSA 10 24 01950 12 28713 240 19500 11 68900 38 01900
Lab 10 9 09740 9 79116 90 97400 0 21800 25 63600
Aqua 9 285 87011 273 88971 2573 7 83300 S40 00000
Simple Statistics Varxable Label
Cap Capture
MHCI MHC-I
MaSR Macrophage scavenger receptor
CysA Cystatin A
KaI 6 Kallikrem 6
AlpS Alpha synuclem
Onctm Osteonectin
01cm Osteocalcin
TroC Troponin C
AbT Abeam Transglutaminase 2
PGRP PGRP-I Beeta
PSA PSA
Lab Labvision Tgase 2
Aqua Aquapoπn-4
Capture Time DATA: Summary table of Aqua by Disease 24 Disease=Cstitis
The CORR Procedure
Pearson Correlation Coefficients Prob > ]r| under HO: Rho=0 Number of Observations
Cap MHCI MaSR CysA KaI6
Cap 1.00000 0.95641 0.82670 0.91453 0 87827 Capture <.0001 0.0032 0.0002 0.0008 10 10 10 10 10
MHCI 0.95641 1.00000 0.90941 0.90916 0.93626 MHC-I ■=.0001 0.0003 0.0003 <.0001 10 10 10 10 10
MaSR 0.82670 0.90941 1.00000 0.67233 0.74594 Macrophage scavenger receptor 0.0032 0.0003 0.0332 0.0132 10 10 10 10 10
CysA 0.91453 0.90916 0.67233 1.00000 0.91639 Cystatm A 0.0002 0.0003 0.0332 0.0002 10 10 10 10 10
Kalβ 0.87827 0.93626 0.74594 0.91639 1.00000 Kallikrem 6 0.0008 <.0001 0.0132 0 0002 10 10 10 10 10
AIpS 0.52544 0.50601 0.70078 0.23659 0.22053 Alpha synuclem 0.1188 0.1356 0.0240 0 5105 0.5404 ' 10 10 10 10 10
Onctm 0.83571 0.83203 0.64072 0.77838 0.91815 Osteonectin 0.0026 0.0028 0.0459 0.0080 0.0002 10 10 10 10 10
01cm 0.87317 0.88057 0.63830 0.91800 0.92637 Osteocalcin 0.0010 0.0008 0.0470 0.0002 0.0001 10 10 10 10 10
TroC 0.80609 0.87799 0.71275 0.81031 0.96820 Troponin C 0.0049 0.0008 0.0207 0.0045 <.0001 10 10 10 10 10
AbT 0.88232 0.92304 0.80190 0.83333 0.91686 Abeam Transglutaminase 2 0.0007 0.0001 0.0053 0.0027 0.0002 10 10 10 10 10
Capture Time DATA: Summary table of Aqua by Disease 25 Disease=Cstitis
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
AIpS Onctm 01cm TroC AbT
Cap 0.52544 0.83571 0.87317 0.80609 0.88232 Capture 0.1188 0.0026 0.0010 0.0049 0.0007
10 10 10 10 10 MHCI 0.50601 0.83203 0.88057 0.87799 0.92304 MHC-I 0.135S 0.0028 0.0008 0.0008 0.0001 10 10 10 10 10
MaSR 0.70078 0.64072 0.63830 0.71275 0.80190 Macrophage scavenger receptor 0.0240 0.0459 0.0470 0.0207 0.0053 10 10 10 10 10
CysA 0.23659 0.77838 0.91800 0.81031 0.83333 Cystatin A 0.5105 0.0080 0.0002 0.0045 0.0027 10 10 10 10 10
KaIS 0.22053 0.91815 0.92637 0.96820 0.91686 Kallikrein 6 0.5404 0.0002 0.0001 <.0001 0.0002 10 10 10 10 10
AIpS 1.00000 0.27066 0.31775 0.21856 0.41225 Alpha synuclein 0.4494 0.3709 0.5441 0.2365 10 10 10 10 10
Onctin 0.27066 1.00000 0.88355 0.93315 0.86389 Osteonectin 0.4494 0.0007 ■=.0001 0.0013 10 10 10 10 10
Olcin 0.31775 0.88355 1.00000 0.89458 0.85062 Osteocalcin 0.3709 0.0007 0.0005 0.0018 10 10 10 10 10
TroC 0.21856 0.93315 0.89458 1.00000 0.88674 Troponin C 0.5441 <.0001 0.0005 0.0006 10 10 10 10 10
AbT 0.41225 0.86389 0.85062 0.88674 1.00000 Abeam Transglutaminase 2 0.2365 0.0013 0.0018 0.0006
10 10 10 10 10
Capture Time DATA: Summary table of Aqua by Disease 26 -~—- Diseasp=(
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations
PGRP PSA Lab Aqua
Cap 0.80845 0.95426 0.31939 0.90753 Capture 0.0046 <.0001 0.3683 0.0007 10 10 10 9
MHCI 0.72160 0.94363 0.19241 0.98088 MHC-I 0.0185 <-0001 0.5944 <.0001 10 10 10 9
MaSR 0.62576 0.75191 0.26245 0.91647
Macrophage scavenger receptor 0.0530 0.0121 0.4638 0.0005 10 10 10 9
CysA 0.59826 0.98627 0.14071 0.82478 Cystatin A 0.0677 <.0001 0.6982 0.0062 10 10 10 9
KaI6 0.68144 0.90268 0.01507 0.92033 Kallikrein 6 0.0300 0.0003 0.9670 0.0004 10 10 10 9
AIpS 0.60121 0.37831 0.41294 0.52221
Alpha synuclein 0.0660 0.2811 0.2356 0.1492 10 10 10 9
Onctin 0.86313 0.77187 0.03567 0.87980 Osteonectin 0.0013 0.0089 0.9221 0.0018 10 10 10 9
Olcin 0.76370 0.91520 0.12575 0.90739 Osteocalcin 0.0101 0.0002 0.7292 0.0007 10 10 10 9
TroC 0.71226 0.80076 0.03652 0.92019 Troponin C 0.0208 0.0054 0.9202 0.0004 10 10 10 9
AbT 0.72102 0.85941 -0.01474 0.95450 Abeam Transglutaminase 2 0.0186 0.0014 0.9578 < .0001 10 10 10 9
Capture Time DATA: Summary table of Aqua by Disease 27 Disease=Cstitis
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
Cap MHCI CysA KaIS
PGRP 0.80845 0.72160 0.62576 0.59826 0.68144
PGRP-I Beeta 0.0046 0.0185 0.0530 0.0677 0.0300 10 10 10 10 10
PSA 0.95426 0.94363 0.75191 0.98627 0.90268 PSA <.0001 <.0001 0.0121 <.0001 0.0003 10 10 10 10 10
Lab 0.31939 0.19241 0.26245 0.14071 0.01507
Labvision Tgase 2 0.3683 0.5944 0.4638 0.6982 0.9670 10 10 10 10 10
Aqua 0.90753 0.98088 0.91647 0.82478 0.92033 Aquaporin-4 0.0007 <.0001 0.0005 0.0062 0.0004 9 9 9 9 9
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
AIpS Onctin Olcin TroC AbT
PGRP 0.60121 0.86313 0.76370 0.71226 0.72102
PGRP-I Beeta 0.0660 0.0013 0.0101 0.0208 0.0186 10 10 10 10 10
PSA 0.37831 0.77187 0.91520 0.80076 0.85941 PSA 0.2811 0.0089 0.0002 0.0054 0.0014 10 10 10 10 10
Lab 0.41294 0.03567 0.12575 0.03652 -0.01474
Labvision Tgase 2 0.2356 0.9221 0.7292 0.9202 0.9678 10 10 10 10 10
Aqua 0.52221 0.87980 0.90739 0.92019 0.95450 Aquaporin-4 0.1492 0.0018 0.0007 0.0004 <.0001 9 9 9 9 9
Capture Time DATA: Summary table of Aqua by Disease Disease=Cstitis
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
PGRP PSA Lab Aqua
PGRP 1.00000 0.65447 0.34242 0.80585
PGRP-I Beeta 0.0400 0.3328 0.0087 10 10 10 9
PSA 0.65447 1.00000 0.20387 0.87132 PSA 0.0400 0.5721 0.0022 10 10 10 9
Lab 0.34242 0.20387 1.00000 0.10452
Labvision Tgase 2 0.3328 0.5721 0.7890 10 10 10 9
Aqua 0.80585 0.87132 0.10452 1.00000 Aquaporin-4 0.0087 0.0022 0.7890 9 9 9 9
Capture Time DATA: Summary table of Aqua by Disease 29 - Disease=Endoaden - The CORR Procedure
14 Variables: Cap MHCI MaSR CysA KaIS AIpS Onctin Olcin TroC AbT PGRP PSA Lab Aqua
Simple Statistics
Variable N Mean Std Dev Sum Minimum Maximum
Cap 10 360.44070 188.93038 3604 14.93600 511.90200
MHCI 10 512.03070 269.78297 5120 0.10700 640.00000
MaSR 10 41.54070 18.59603 415.40700 11.78400 76.91000
CysA 10 21.58380 9.26001 215.83800 2.97300 29.38200
KaI6 10 1.79480 1.00869 17.94800 0.09300 2.88000
AIpS 10 36.71480 12.97864 367.14800 10.90800 46.65600
Onctin 10 1.11450 0.58642 11.14500 0.34200 2.38700
Olcin 10 2.71050 1.44573 27.10500 0 3.84200
TroC 10 0.95020 0.53733 9.50200 0 1.49000
AbT 10 0.33550 0.37329 3.35500 0 1.11800
PGRP 10 512.19500 269.43699 5122 0 640.00000
PSA 10 34.50430 18.23594 345.04300 0.03600 46.26100
Lab 10 3.28460 3.00742 32.84600 0 8.64500
Aqua S 480.00000 296.26243 3840 0 640.00000
Simple Statistics
Variable Label
Cap Capture
MHCI MHC-I
MaSR Macrophage scavenger receptor
CysA Cystatin A
KaI6 Kallikrein 6
AIpS Alpha synuclein
Onctin Osteonectin
Olcin Osteocalcin
TroC Troponin C
AbT Abeam Transglutaminase 2
PGRP PGRP-I Beeta
PSA PSA
Lab Labvision Tgase 2
Aqua Aquaporin-4
Capture Time DATA: Summary table of Aqua by Disease 30
- Disease=Endoaden
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations
Cap MHCI MaSR CysA KaI6
Cap 1.00000 0.96376 0.84037 0.93959 0.75633 Capture <.0001 0.0023 <.0001 0.0114 10 10 10 10 10
MHCI 0.96376 1.00000 0.82606 0.97574 0.74291 MHC-I <.0001 0.0032 ■=.0001 0.0138 10 10 10 10 10
MaSR 0.84037 0.82606 1.00000 0.85034 0.46638 Macrophage scavenger receptor 0.0023 0.0032 0.0018 0.1742 10 10 10 10 10
CysA 0.93959 0.97574 0.85034 1.00000 0.61080 Cystatin A <.0001 <.0001 0.0018 0.0607 10 10 10 10 10
KaI6 0.75633 0.74291 0.46638 0.61080 1.00000 Kallikrein 6 0.0114 0.0138 0.1742 0.0607 10 10 10 10 10
AIpS 0.96541 0.97717 0.85665 0.98239 0.68743 Alpha synuclein ■=.0001 <-0001 0.0015 <.0001 0.0280 10 10 10 10 10
Onctin 0.68432 0.65249 0.62803 0.60834 0.73335 Osteonectin 0.0291 0.0409 0.0519 0.0620 0.0158 10 10 10 10 10 Olcin 0.94440 0.95331 0.82627 0.88595 0.84359
Osteocalcin <.O001 <.0001 0.0032 0.0006 0.0022
10 10 10 10 10
TroC 0.87441 0.88642 0.55715 0.79901 0.93146
Troponin C 0.0009 0.0006 0.0943 0.0056 <.0001
10 10 10 10 10
AbT 0.29201 0.40805 0.26835 0.37351 0.44274
Abeam Transglutaminase 2 0.4130 0.2418 0.4535 0.2877 0.2001
10 10 10 10 10
Capture Time DATA: Summary table of Aqua by Disease 31 Disease=Endoaden ->
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
AIpS Onctin Olcin AbT
Cap 0.96541 0.68432 0.94440 0.87441 0.29201 Capture <.0001 0.0291 <.0001 0.0009 0.4130 10 10 10 10 10
MHCI 0.97717 0.65249 0.95331 0.88642 0.40805 MHC-I <.0001 0.0409 <.0001 0.0006 0.2418 10 10 10 10 10
MaSR 0.85665 0.62803 0.82627 0.55715 0.26835 Macrophage scavenger receptor 0.0015 0.0519 0.0032 0.0943 0.4535 10 10 10 10 10
CysA 0.98239 0.60834 0.88595 0.79901 0.37351 Cystatin A <.0001 0.0620 0.0006 0.0056 0.2877 10 10 10 10 10
KaI6 0.68743 0.73335 0.84359 0.93146 0.44274 Kallikrein 6 0.0280 0.0158 0.0022 <.0001 0.2001 10 10 10 10 10
AIpS 1.00000 0.67143 0.92545 0.83936 0.42979 Alpha synuclein 0.0335 0.0001 0.0024 0.2151 10 10 10 10 10
Onctin 0.67143 1.00000 0.67134 0.71616 0.59940 Osteonectin 0.0335 0.0335 0.0198 0.0670 10 10 10 10 10
Olcin 0.92545 0.67134 1.00000 0.88669 0.39437 Osteocalcin 0.0001 0.0335 0.0006 0.2594 10 10 10 10 10
TroC 0.83936 0.71616 0.88S69 1.00000 0.42242 Troponin C 0.0024 0.0198 0.0006 0.2239 10 10 10 10 10
AbT 0.42979 0.59940 0.39437 0.42242 1.00000 Abeam Transglutaminase 2 0.2151 0.0670 0.2594 0.2239 10 10 10 10 10
Capture Time DATA: Summary table of Aqua by Disease 32 Disease=Endoaden
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
PGRP PSA Lab Aqua
Cap 0. 96376 0 .97122 -0.14327 0 .96445 Capture < .0001 ■=.0001 0.6929 0.0001
10 10 10 8
MHCI 1. 00000 0 .99619 -0.06446 1 .00000 MHC-I < .0001 •=.0001 0.8596 <.0001
10 10 10 8
MaSR 0. 82603 0 .83295 0.18383 0 .97386 Macrophage scavenger receptor 0 0032 0.0028 0 6112 < 0001 10 10 10 8
Cy sA 0.97S8S 0.98012 -0.05370 0 98303 Cystatm A <.0001 <.0001 0.8829 < 0001 10 10 10 8
Kal6 0.74312 0.72410 -0.08313 0.79327 Kallikrem 6 0.0138 0 0179 0.8194 0.0188 10 10 10 8
AIpS 0.97727 0.98881 0.01686 0.98434 Alpha synuclem .= .0001 <.0001 0.9631 <.0001 10 10 10 8
Onctxn 0.65255 0.65235 0.00868 0.63375 Osteonectin 0.0408 0.0409 0.9810 0.0916 10 10 10 8
01cm 0.9533S 0.94703 0.04880 0.95813 Osteocalcin <.0001 .= .0001 0.8935 0.0002 10 10 10 8
TroC 0.88S48 0.87231 -0.19613 0.94818 Troponin C 0.0006 0.0010 0.5871 0.0003 10 10 10 8
AbT 0.40814 0.41668 0.47827 0.39427 Abeam Transglutaminase 2 0.2416 0.2310 0.1620 0.3338 10 10 10 8
Capture Time DATA: Summary table of Aqua by Disease 33
Tin α£»a eρ»=TϋnHr>ΛrIρ
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO: Rho=0 Number of Observations
Cap MHCI MaSR CysA Kal6
PGRP 0.96376 1.00000 0 82603 0.97586 0.74312
PGRP-I Beeta ■=.0001 <.0001 0.0032 <.0001 0.0138
10 10 10 10 10
PSA 0.97122 0.99619 0.83295 0.98012 0.72410 PSA ■=.0001 <.0001 0.0028 <.0001 0.0179 10 10 10 10 10
Lab -0.14327 -0.06446 0.18383 -0.05370 -0.08313
Labvision Tgase 2 0.6929 0.8596 0.6112 0.8829 0.8194 10 10 10 10 10
Aqua 0.96445 1.00000 0.97386 0.98303 0.79327 Aquaporm-4 0.0001 <.0001 <.0001 ■=.0001 0.0188 8 8 8 8 8
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
AIpS Onctm 01cm TroC AbT
PGRP 0.97727 0.65255 0.95336 0.88648 0.40814
PGRP-I Beeta ■=.0001 0.0408 <.0001 0.0006 0.2416 10 10 10 10 10
PSA 0.98881 0.65235 0.94703 0.87231 0.41668 PSA <.0001 0.0409 ■=.0001 0.0010 0.2310 10 10 10 10 10
Lab 0.01686 0.00868 0.04880 -0.19613 0.47827
Labvision Tgase 2 0.9631 0.9810 0.8935 0.5871 0.1620 10 10 10 10 10
Aqua 0.98434 0.6337S 0.95813 0.94818 0.39427 Aquaporin-4 <.0001 0.0916 0.0002 0.0003 0.3338 8 8 8 8 8
Capture Time DATA: Summary table of Aqua by Disease 34
Disease=Endoaden The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO Rho=0 Number of Observations
PGRP PSA Lab Aqua
PGRP 1 00000 0 99618 -0 06419 1 00000
PGRP-I Beeta < 0001 0 8602 < 0001
10 10 10
PSA 0 99618 1 00000 -0 05250 0 99672 PSA < 0001 0 8855 < 0001
10 10 10
Lab -0 06419 -0 05250 1 00000 -0 16265
Labvision Tgase 2 0 8602 0 8855 0 7004
10 10 10 8
Aqua 1 00000 0 99672 -0 16265 1 00000 Aquaporin-4 < 0001 < 0001 0 7004
8
Capture Time DATA Summary table of Aqua by Disease 35
- Disease=KidSton -- The CORR Procedure 4 Variables Cap MHCI MaSR CysA KaIS AIpS Onctin 01cm AbT PGRP PSA Lab Aqua
Simple Statistics
Variable N Mean Std Dev Sum Minimum Maximum
Cap 10 95 16090 17 20700 951 60900 64 14100 118 40900
MHCI 10 41 84380 8 74930 418 43800 24 44000 51 97800
MaSR 10 38 40090 6 94747 384 00900 22 01900 45 20800
CysA 10 3 96070 1 84093 39 60700 1 58300 6 99600
KaI6 10 0 20520 0 15723 2 05200 0 0 46600
AIpS 10 15 75160 3 69162 157 51600 9 85300 21 67400
Onctm 10 0 32340 0 10558 3 23400 0 24900 0 52800
01cm 10 0 13640 0 13484 1 36400 0 0 40900
TroC 10 0 06530 0 13940 0 65300 0 0 37300
AbT 10 0 04660 0 09067 0 4S600 0 0 28000
PGRP 10 55 48600 11 25769 554 86000 31 53500 68 32000
PSA 10 4 33550 0 51775 43 35500 3 26800 4 95600
Lab 9 2 64822 4 61973 23 83400 0 14 34200
Aqua 10 54 23880 10 56889 542 38800 33 69100 65 62000
Simple Statistics
Variable Label
Cap Capture
MHCI MHC-I
MaSR Macrophage scavenger receptor
CysA Cystatm A
Kal6 Kallikrem 6
AIpS Alpha synuclem
Onctm Osteonectin
Olcin Osteocalcin
TroC Troponin C
AbT Abeam Transglutaminase 2
PGRP PGRP-I Beeta
PSA PSA
Lab Labvision Tgase 2
Aqua Aquaporin-4
Capture Time DATA Summary table of Aqua by Disease 36 Disease=KidSton
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO RhO=O Number o£ Observations
Cap MHCI MaSR CysA KaI6 Cap 1.00000 0.S9283 0.61847 0 42444 -0 21123 Capture 0.0263 0.056S 0 2215 0 5580 10 10 10 10 10
MHCI 0.69283 1.00000 0.75367 0.09322 0.22823 MHC-I 0.0263 0 0118 0.7979 0.5260 10 10 10 10 10
MaSR 0.61847 0.75367 1 00000 0 34193 -0.02822 Macrophage scavenger receptor 0.0566 0 0118 0.3335 0.9383 10 10 10 10 10
CysA 0.42444 0.09322 0.34193 1.00000 0.19813 Cystatin A 0.2215 0 7979 0.3335 0.5832 10 10 10 10 10
KaI6 -0.21123 0 22823 -0.02822 0.19813 1.00000 Kallikrem S 0.5580 0.5260 0.9383 0.5832 10 10 10 10 10
AIpS 0.77161 0.36158 0.60763 0.76271 -0.15288 Alpha synuclein 0.0089 0.3046 0.0624 0.0103 0.6733 10 10 10 10 10
Onetin -0.54737 -0.43340 -0.71135 -0.26351 0.31459 Osteonectin 0.1015 0.2108 0.0211 0.4620 0.3760 10 10 10 10 10
01cm -0.23124 0.22114 0.01920 0.23146 0.74621 Osteocalcin 0.5203 0.5392 0.9S80 0.5200 0.0132 10 10 10 10 10
TroC -0.01212 -0.25605 -0.01617 -0.11260 -0.32568 Troponin C 0.9735 0.4752 0.9646 0.7568 0.3584 10 10 10 10 10
AbT -0.40960 -0 55546 -0.79005 0.03998 0.06800 Abeam Transglutaminase 2 0.2398 0.0955 0.0065 0.9127 0.8519 10 10 10 10 10
Capture Time DATA: Summary table of Aqua by Disease 37
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of observations
AIpS Onctm 01cm TroC AbT
Cap 0.77161 -0.54737 -0.23124 0.01212 -0.40960 Capture 0.0089 0.1015 0.5203 0.9735 0.2398
10 10 10 10 10
MHCI 0.36158 -0.43340 0.22114 0.25605 -0.55546 MHC-I 0.3046 0.2108 0.5392 0.4752 0.0955
10 10 10 10 10
MaSR 0.60763 -0.71135 0.01920 0.01617 -0.79005
Macrophage scavenger receptor 0.0624 0.0211 0.9580 0.9646 0.0065
10 10 10 10 10
CysA 0.76271 -0.26351 0.23146 0.11260 0.03998 Cystatin A 0.0103 0.4620 0.5200 0.7568 0.9127
10 10 10 10 10
KaI6 -0.15288 0.31459 0.74621 0.32568 0.06800 Kallikrein 6 0.6733 0.3760 0.0132 0.3584 0.8519
10 10 10 10 10
Alps 1.00000 -0.67662 -0.03392 0.13684 -0.45005
Alpha synuclein 0.0317 0.9259 0.7062 0.1919
10 10 10 10 10
Onctm -0.67662 1.00000 0.03978 0.15699 0.70510 Osteonectin 0.0317 0.9131 0.6649 0.0228
10 10 10 10 10
01cm -0.03392 0.03978 1.00000 0.52651 0.06981 Osteocalcin 0.9259 0.9131 0.1179 0.8480
10 10 10 10 10
TroC 0.13684 0.15699 -0.52651 1.00000 -0.26752 Troponin C 0.7062 0.6649 0.1179 0.4549 10 10 10 10 10
AbT -0.4S005 0.70510 0.06981 -0.267S2 1.00000 Abeam Tr;msglutaminase 2 0.1919 0.0228 0.8480 0.4549 10 10 10 10 10
Capture Time DATA: Summary table of Aqua by Disease 38 fnrtRhnπ -.
The CORR procedure
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
PGRP PSA Lab Aqua
Cap 0.75S49 0.65187 0.55551 0.86384 Capture 0.0113 0.0411 0.1205 0.0013 10 10 9 10
MHCI 0.93S17 0.84620 -0.10550 0.91965 MHC-I <.0001 0.0020 0.7871 0.0002 10 10 9 10
MaSR 0.77649 0.57646 0.10460 0.76161 Macrophage scavenger receptor 0.0083 0.0811 0.7888 0.0105 10 10 9 10
CysA 0.18204 -0.20022 0.46254 0.33460 Cystatin A 0.6147 0.S791 0.2100 0.3446 10 10 9 10
KaIS 0.16819 0.03654 -0.50114 0.08297 Kallikrein 6 0.6423 0.9202 0.1693 0.8197 10 10 9 10
AIpS 0.52134 0.24395 0.79340 0.62853 Alpha synuclein 0.1223 0.4970 0.0107 0.0516
10 10 9 10
Onctin -0.50342 -0.41605 -0.39573 -0.57265 Osteonectin 0.1380 0.2317 0.2918 0.0836 10 10 9 10
Olcin 0.21775 -0.00988 -0.27813 0.17747 Osteocalcin 0.5456 0.9784 0.4687 0.6238 10 10 9 10
TroC -0.13991 -0.13071 0.42422 -0.26905 Troponin C 0.6999 0.7189 0.2551 0.4522 10 10 9 10
AbT -0.66677 -0.64255 -0.24182 -0.53312 Abeam Transglutaminase 2 0.0352 0.0451 0.5307 0.1126 10 10 9 10
Capture Time DATA: Summary table ooff AAqαuuaa bbyv Disease Disease=KidSton
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
Cap MHCI MaSR CysA KaI6
PGRP 0.75649 0.93617 0.77649 0.18204 0.16819
PGRP-I Beeta 0.0113 •=.0001 0.0083 0.6147 0.6423 10 10 10 10 10
PSA 0.65187 0.84620 0.57646 -0.20022 0.03654 PSA 0.0411 0.0020 0.0811 0.5791 0.9202 10 10 10 10 10
Lab 0.55551 -0.10550 0.10460 0.46254 -0.50114
Labvision Tgase 2 0.1205 0.7871 0.7888 0.2100 0.1693 9 9 9 9 9
Aqua 0.86384 0.91965 0.76161 0.33460 0.08297 Aquaporin-4 0.0013 0.0002 0.0105 0.3446 0.8197 10 10 10 10 10 Pearson Correlation Coefficients Prob > |r] under HO. Rho=0 Number of Observations
AIpS Onctm Olcin TroC AST
PGRP 0.52134 -0.50342 0.21775 -0.13991 -0.66677
PGRP-I Beeta 0.1223 0.1380 0.5456 0.6999 0.0352 10 10 10 10 10
PSA 0.24395 -0.41605 -0.00988 -0.13071 -0.64255 PSA 0.4970 0 2317 0.9784 0.7189 0.0451 10 10 10 10 10
Lab 0.79340 -0 39573 -0.27813 0.42422 -0.24182
Labvision Tgase 2 0.0107 0.2918 0.4687 0.2551 0.5307 9 9 9 9 9
Aqua 0.62853 -0 57265 0.17747 -0.26905 -0.53312 Aquapoπn-4 0.0516 0.0836 0.6238 0.4522 0.1126 10 10 10 10 10
Capture Time DATA: Summary table of Aqua by Disease Disease=KidSton
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
PGRP PSA Lab Aqua
PGRP 1 00000 0.88435 0.17987 0.95761
PGRP-I Beeta 0.0007 0.6433 •c.OOOl 10 10 9 10
PSA 0 88435 1.00000 0.09052 0.81472 PSA 0.0007 0.8168 0.0041 10 10 9 10
Lab 0.17987 0.09052 1.00000 0.23673
Labvision Tgase 2 0.6433 0.8168 0.5397 9 9 9 9
Aqua 0.95761 0.81472 0.23673 1.00000 Aquaponn-4 •=.0001 0.0041 0.5397 10 10 9 10
Capture Time DATA: Summary table of Aqua by Disease 41
- Disease=Parkmso - The CORR Procedure
14 Variables : Cap MHCI MaSR CysA KaI6 AIpS Onctm 01cm TroC
AbT PGRP PSA Lab Aqua
Simple Statistics
Variable N Mean Std Dev Sum Minimum Maximum
Cap 10 140.76800 4.79112 1408 132.68700 149.97200
MHCI 10 75.27820 2.40413 752.78200 72.06000 78.48000
MaSR 10 20.93600 1.93571 209.36000 17.25600 24.59900
CysA 10 3.44330 0.28307 34.43300 2.97300 3.89500
KaI6 10 2.60260 0.30483 26.02600 2.41800 3.43400
AIpS 10 24.57190 1.30393 245.71900 23.74100 28.18900
Onctm 10 2.88520 0.72984 28.85200 2.20100 4.04800
01cm 10 2.56660 0.61919 25.66600 1.59100 3.19700
TroC 10 2.54700 0.30273 25.47000 2.23200 3.15700
AbT 10 3.07390 0.42222 30.73900 2.69500 4.17000
PGRP 10 83.54920 6.30202 835.49200 71.95300 92.86900
PSA 10 12.41210 0.57932 124.12100 11.99800 13.82000
Lab 10 0.46160 0.11950 4.61600 0.36400 0.69000
Aqua 10 88.73120 4.65456 887.31200 83.43500 96.41800
Simple Statistics
Variable Label Cap Capture
MHCI MHC-I
MaSR Macrophage scavenger receptor
CysA Cystatm A
Kal6 Kallikrem 6
AIpS Alpha synuclem
Onctm Osteonectin
01cm Osteocalcin
TroC Troponin C
AbT Abeam Transglutaminase 2
PGRP PGRP-I Beeta
PSA PSA
Lab Labvision Tgase 2
Aqua Aquapoπn-4
Capture Time DATA: Summary table of Aqua by Disease 42
Figure imgf000399_0001
The CORR Procedure
Pearson Correlation Coefficients, N = 10 Prob > I r1 under HO : Rho=
Cap MHCI MaSR CysA KaI 6
Cap 1.00000 0.40729 0.32739 0.13402 0.11594
Capture 0.2427 0.3558 0.7120 0.7498
MHCI 0.40729 1.00000 0.59675 0.36542 0.41736
MHC-I 0.2427 0.0686 0.2991 0.2301
MaSR 0.32739 0.59675 1.00000 0.49821 0.70498
Macrophage scavenger receptor 0.3558 0.0686 0.1428 0.0228
CysA 0.13402 0.36542 0.49821 1.00000 -0.08738
Cystatm A 0.7120 0.2991 0.1428 0.8103
KaI 6 0.11594 0.41736 0.70498 -0.08738 1.00000
Kallikrein 6 0.7498 0 2301 0.0228 0.8103
Alps 0.11346 0.52543 0.69683 -0.06779 0.93627
Alpha synuclein 0.7550 0.1188 0.0251 0.8524 ■c.OOOl
Onctm 0.05742 -0.14166 0.28106 -0.30809 0.65152
Osteonectin 0.8748 0.6963 0.4315 0.3865 0.0413
01cm 0.37458 0.61922 0.05486 0.15567 0.14529
Osteocalcin 0.28S2 0.0563 0.8804 0.6676 0.6888
TroC 0.30886 0.75048 0.73720 0.22803 0.66836
Troponin C 0.3852 0.0124 0.0150 0.5263 0.0346
AbT 0.48667 0.54392 0.29415 -0.15789 0.18430
Abeam Transglutaminase 2 0.1537 0.1041 0.4094 0.6631 0.6103
PGRP 0.38247 -0.23058 -0.19406 -0.30086 -0.31852
PGRP-I Beeta 0.2754 0.5216 0.5911 0.3983 0.3697
PSA -0.10871 0.49744 0.75491 0.27017 0.81303
PSA 0.7650 0.1435 0.0116 0.4503 0.0042
Lab -0.10739 -0.43033 -0 12240 0.10362 -0.12164
Labvision Tgase 2 0.7678 0.2145 0.7362 0.7758 0.7378
Aqua -0.26871 -0.29200 -0.42779 -0.44809 0.08336
Aquapoπn-4 0.4528 0.4130 0.2175 0.1940 0.8189
Capture Time DATA: Summary table of Aqua by Disease 43 Disease=Parkmso
The CORR Procedure
Pearson Correlation Coefficients, N = 10 Prob > |r| under HO: Rho=o
AIpS Onctm 01cm TroC AbT
Cap 0.11346 0.05742 0.37458 0.30886 0.48667 Capture 0.7550 0.8748 0.2862 0.3852 0.1537
MHCI 0.52543 -0.14166 0.61922 0.75048 0.54392 MHC-I 0.1188 0.6963 0.0563 0.0124 0.1041 MaSR 0.69683 0 28106 0 05486 0 73720 0 29415 Macrophage scavenger receptor 0.0251 0 431S 0.8804 0.0150 0.4094
CysA -0.06779 -0.30809 0.15567 0.22803 -0.15789 Cystatm A 0.8524 0.3865 0.6676 0.5263 0.6631
KaIS 0.93627 0.65152 0.14529 0.66336 0.18430 Kallikrem 6 <.oooi 0.0413 0.6888 0.0346 0.6103
AIpS 1 00000 0 46561 0.21582 0.73704 0.24337 Alpha synuclem 0 1750 0.5493 0.0150 0.4981
Onctxn 0.46561 1 00000 0.01110 0.34165 0 15943 Osteonectin 0.1750 0.9757 0.3339 0.6600
01cm 0 21582 0.01110 1.00000 0.56110 0.22243 Osteocalcin 0.5493 0.9757 0.0915 0.5368
TroC 0.73704 0.34165 0.56110 1.00000 0 54689 Troponin C 0.0150 0.3339 0.0915 0.1019
AbT 0.24337 0.15943 0.22243 0.54689 1.00000 Abeam Transglutaminase 2 0.4981 0.6600 0.5368 0.1019
PGRP -0.31801 -0.10663 -0 38152 -0.47197 0.15215 PGRP-I Beeta 0.3705 0.7694 0.2767 0.1684 0.6748
PSA 0.83712 0.38239 0.28814 0.80194 0.02259 PSA 0.0025 0.2755 0.4195 0.0053 0.9506
Lab -0.20676 0.10686 -0.38236 -0.23383 -0.06547 Labvision Tgase 2 0.5666 0.7689 0.2755 0.5156 0.8574
Aqua 0.14421 0.25295 0.37833 -0.02862 -0.42585 Aquaporm-4 0.6910 0.4807 0.2810 0.9374 0.2198
Capture Time DATA: Summary table of Aqua by Disease 44 Disease=Parkmso
The CORR Procedure
Pearson Correlation Coefficients, N = 10 Prob > |r| under HO: Rho=0
PGRP PSA Lab Aqua
Cap 0.38247 -0.10871 -0.10739 -0.26871
Capture 0.2754 0.7650 0.7678 0.4528
MHCI -0.23058 0.49744 -0.43033 -0.29200
MHC-I 0.5216 0.1435 0.2145 0.4130
MaSR -0.19406 0.75491 -0.12240 -0.42779
Macrophage scavenger receptor 0.5911 0.0116 0.7362 0.2175
CysA -0.30086 0.27017 0.10362 -0.44809
Cystatm A 0.3983 0.4503 0.7758 0.1940
Kal6 -0.31852 0.81303 -0.12164 0.08336
Kallikrein 6 0.3697 0.0042 0.7378 0.8189
Alps -0.31801 0.83712 -0.20676 0.14421
Alpha synuclem 0.3705 0.0025 0.5666 0.6910
Onctin -0.10663 0.38239 0.10686 0.25295
Osteonectin 0.7694 0.2755 0.7689 0.4807
01cm -0.38152 0.28814 -0.38236 0.37833
Osteocalcin 0.2767 0.4195 0.2755 0.2810
TroC -0.47197 0.80194 -0.23383 -0.02862
Troponin C 0.1684 0.0053 0.5156 0.9374
AbT 0.15215 0.02259 -0.06547 -0.42585
Abeam Transglutaminase 2 0.6748 0.9506 0.8574 0.2198
PGRP 1.00000 -0.64289 -0.30951 -0.22524
PGRP-I Beeta 0.0450 0.3842 0.5315
PSA -0.64289 1.00000 -0.17663 0.14115
PSA 0.0450 0.6254 0.6973
Lab -0.30951 -0.17663 1.00000 -0.24482 Labvision Tgase 2 0 3842 0 6254 0 4954
Aqua -0.22524 0.14115 -0.24482 1 00000 Aquaponn-4 0.5315 0.6973 0.4954
Capture Time DATA: Summary table of Aqua by Dxsease 45
- Disease=Prostate - The CORR Procedure
14 Variables - Cap MHCI MaSR CysA Kal6 AIpS Onctm 01cm TroC AbT PGRP PSA Lab Aqua
Simple Statistics
Variable N Mean Std Dev Sum Minimum Maximum
Cap 10 7.29580 5.26111 72.95800 2.85800 17.34900
MHCI 10 0.37690 0.32405 3.76900 0.01300 1.03800
MaSR 9 12.90044 2.60770 116.10400 10.20500 16.39000
CysA 10 4 49120 5.30736 44.91200 0.18700 13.70100
KaI 6 10 0.25190 0.14597 2.51900 0.09300 0.55900
Alps 10 5.73920 3.94053 57.39200 0 10.20500
Onctm 10 0.43520 0.14576 4.35200 0.24900 0.71500
01cm 10 0 0 0 0 0
TroC 10 0.11190 0.22335 1.11900 0 0.65300
AbT 10 0.07450 0.08573 0.74500 0 0.28000
PGRP 10 1.03370 1.64244 10.33700 0 5.13100
PSA 10 0.25420 0.20553 2.54200 0.03S00 0.47200
Lab 10 1.12160 1.52791 11.21600 0 3.65700
Aqua 10 0.49200 0.50196 4.92000 0 1.32300
Simple Statistics
Variable Label
Cap Capture
MHCI MHC-I
MaSR Macrophage scavenger receptor
CysA Cystatm A
Kal6 Kallikrem 6
AIpS Alpha synuclem
Onctm Osteonectin
01cm Osteocalcin
TroC Troponin C
AbT Abeam Transglutaminase 2
PGRP PGRP-I Beeta
PSA PSA
Lab Labvision Tgase 2
Aqua Aquaponn-4
Capture Time DATA: Summary table of Aqua by Disease 46 Disease=Prostate
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
Cap MHCI MaSR CysA KaI 6
Cap 1.00000 0.17724 -0.33618 -0.48848 0.42208 Capture 0.6242 0.3764 0.1520 0.2244 10 10 9 10 10
MHCI 0.17724 1.00000 0.69645 -0.10621 0.54427
MHC-I 0.6242 0.0371 0.7703 0.1038 10 10 9 10 10
MaSR -0.33618 0.69645 1.00000 0.12921 -0.50955 Macrophage scavenger receptor 0.3764 0.0371 0.7404 0.1611 9 9 9 9 9
CysA -0.48848 -0.10621 0.12921 1.00000 -0.34519 Cystatm A 0.1520 0.7703 0.7404 0.3286 10 10 9 10 10
Kal6 0.42208 0.54427 -0.50955 -0.34519 1.00000 Kallikrem 6 0.2244 0.1038 0.1611 0.3286 10 10 9 10 10 AIpS -0 49137 -0 07041 0 S7993 0 02676 -0 76164 Alpha synuclein 0 1492 0 8467 0 0439 0 9415 0 0105 10 10 9 10 10
Onetin -0 11502 -0 02118 0 38860 -0 16763 0 49858 Osteonectin 0 7517 0 9537 0 3013 0 6434 0 1424 10 10 9 10 10
01cm Osteocalcin
10 10 9 10 10
TroC 0 39425 -0 18410 0 30405 -0 05819 -0 22025 Troponin C 0 2596 0 SlOS 0 4263 0 8731 0 5409 10 10 9 10 10
AbT 0 03154 0 58396 0 44987 0 05112 0 03146 Abeam Transglutaminase 2 0 9311 0 07S3 0 2244 0 8885 0 9312 10 10 9 10 10
Capture Time DATA Summary table of Aqua by Disease Disease=Prostate
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO Rho=0 Number of Observations
AIpS Onctm Olciix TroC AbT
Cap -0 49137 -0 11502 -0 39425 0 03154 Capture 0 1492 0 7517 0 2596 0 9311 10 10 10 10
MHCI -0 07041 0 02118 -0 18410 0 58396 MHC I 0 8467 0 9537 0 6106 0 0763 10 10 10 10
MaSR 0 67993 -0 38860 0 30405 0 44987 Macrophage scavenger receptor 0 0439 0 3013 0 4263 0 2244 9 9 9 9
CysA 0 02676 0 16763 -0 05819 0 05112 Cystatin A 0 9415 0 6434 0 8731 0 8885 10 10 10 10
Kal6 0 76164 0 49858 -0 22025 0 03146 Kallikrein 6 0 0105 0 1424 0 5409 0 9312 10 10 10 10 10
AIpS 1 00000 -0 33057 0 12742 0 26730 Alpha synuclein 0 3509 0 7257 0 4553 10 10 10 10 10
Onctin -0 33057 1 00000 0 11890 -0 15514 Osteonectin 0 3509 0 7435 0 6687 10 10 10 10
01cm Osteocalcin
10 10 10 10
TroC 0 12742 0 11890 1 00000 -0 33266 Troponin C 0 7257 0 7435 0 3476
10 10 10 10 10
AbT 0 26730 -0 15514 -0 33266 1 00000
Abeam Transglutaminase 2 0 4553 0 6687 0 3476
10 10 10 10
Capture Time DATA Summary table of Aqua by Disease 48 Disease=Prostate
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO RhO=O Number of Observations
PGRP PSA Lab Aqua
Cap -0 29751 -0 31933 0 .13579 -0 35832 Capture 0.4038 0.3685 0.7084 0.3093 10 10 10 10
MHCI 0.33086 0.60982 -0.45848 -0.20438 MHC-I 0.3504 0.0612 0.1826 0.5711 10 10 10 10
MaSR 0.S9740 0.59381 -0.26097 0.03778
Macrophage scavenger receptor 0.0368 0.0918 0.4976 0.9231 9 9 9 9
CysA 0.37478 -0.06584 0.13492 -0.57072 Cystatin A 0.2859 0.8566 0.7102 0.0849 10 10 10 10
KaI6 -0.43377 -0.00002 -0.25307 0.04596 Kallikrein S 0.2104 1.0000 0.4805 0.8997 10 10 10 10
AIpS 0.45679 0.57981 -0.06024 0.21474
Alpha synuclein 0.1845 0.0789 0.8687 0.5513 10 10 10 10
Onctin -0.40936 0.14970 -0.41988 0.27743 Osteonectin 0.2401 0.6798 0.2270 0.4377 10 10 10 10
Oloin Osteocalcin
10
TroC 0.26471 -0.14670 -0.35569 0.45394 Troponin C 0.4598 0.6859 0.3131 0.1876
10 10 10 10
AbT 0.63779 0.64027 -0.41866 -0.21907
Abeam Transglutaminase 2 0.0473 0.0461 0.2285 0.5431
10 10 10 10
Capture Time DATA: Summary table of Aqua by Disease 49
- Disease=Prostate - The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
Cap MHCI MaSR CysA KaI6
PGRP -0.29751 0.33086 0.69740 0.37478 -0.43377
PGRP-I Beeta 0.4038 0.3504 0.0368 0.2859 0.2104 10 10 9 10 10
PSA -0.31933 0.60982 0.59381 -0.06584 -0.00002 PSA 0.3685 0.0612 0.0918 0.8566 1.0000 10 10 9 10 10
Lab 0.13579 -0.45848 -0.26097 0.13492 -0.25307
Labvision Tgase 2 0.7084 0.1826 0.4976 0.7102 0.4805 10 10 9 10 10
Aqua -0.35832 -0.20438 0.03778 -0.57072 0.04596 Aquaporin-4 0.3093 0.5711 0.9231 0.0849 0.8997 10 10 9 10 10 son Correlation Coefficients rob > r| under HO: RhO=O
Number of Observations
AIpS Onctin Olcin TroC AbT
PGRP 0.45679 -0.40936 0.26471 0.63779
PGRP-I Beeta 0.1845 0.2401 0.4598 0.0473
10 10 10 10 10
PSA 0.57981 0.14970 0.14670 0.64027 PSA 0.0789 0.6798 0.6859 0.0461
10 10 10 10 10
Lab -0.06024 -0.41988 0.35569 -0.41866
Labvision Tgase 2 0.8687 0.2270 0.3131 0.2285
10 10 10 10 10
Aqua 0.21474 0.27743 0.45394 -0.21907 Aquapoπn-4 5513 0 4377 0.1876 0 5431 10 10 10 10
Capture Time DATA: Summary table of Aqua by Disease 50 Disease=Prostate
The CORR Procedure
Pearson Correlation Coefficients Prob > |r| under HO: RhO=O Number of Observations
PGRP PSA Lab Aqua
PGRP 1.00000 0 3839B -0.28960 -0.29585
PGRP-I Beeta 0.2733 0.4170 0.4066
10 10 10 10
PSA 0.38398 1.00000 -0.58122 0.08793 PSA 0.2733 0.0780 0 8091
10 10 10 10
Lab -0.289SO -0.S8122 1.00000 -0.17247
Labvision Tgase 2 0.4170 0.0780 0.6337
10 10 10 10
Aqua -0.29585 0.08793 -0.17247 1.00000 Aquapoπn-4 0.4066 0.8091 0.6337
10 10 10 10
Capture Time DATA: Summary table of Aqua by Disease
- Disease=Prostati - The CORR Procedure
14 Variables : Cap MHCI MaSR CysA KaI6 AIpS Onctin 01cm TroC
AbT PGRP PSA Lab Aqua
Simple Statistics
Variable N Mean Std Dev Sum Minimum Maximum
Cap 10 521.09460 128.07561 5211 359.19200 640.00000
MHCI 10 468.35620 198.75867 4684 161.30300 640.00000
MaSR 10 25.42470 9.46639 254. 24700 13.17900 40.88900
CysA 10 25.46760 2.74424 254. 67600 22.36400 31.76400
KaI6 10 0.81990 0.47641 8. 19900 0.09300 1.58300
AIpS 10 35.09740 8.17385 350. 97400 22.70900 47.93900
Onetin 10 0.96590 0.32558 9. 65900 0.52800 1.64500
01cm 10 2.11220 0.81542 21. 12200 1.16900 3.41800
TroC 10 0.64320 0.28267 6. 43200 0.28000 1.21100
AbT io 0.51210 0.69392 5. 12100 0 1.76800
PGRP 10 387.16540 267.57223 3872 96.45500 640.00000
PSA 10 40.41940 3.35955 404. 19400 35.13200 45.14300
Lab 10 0.46470 0.41452 4. 64700 0 1.30400
Aqua 10 413.84040 245 35230 4138 107.04900 640.00000
Simple Statistics
Variable Label
Cap Capture
MHCI MHC-I
MaSR Macrophage scavenger receptor
CysA Cystatin A
KaI6 Kallikrein 6
AIpS Alpha synuclem
Onctm Osteonectin
01cm Osteocalcin
TroC Troponin C
AbT Abeam Transglutaminase 2
PGRP PGRP-I Beeta
PSA PSA
Lab Labvision Tgase 2
Aqua Aquapoπn-4
Capture Time DATA: Summary table of Aqua by Disease 52
Disease=Prostati The CORR Procedure
Pearson Correlation Coefficients, N = 10 Prob > |r| under HO RhO=O
Cap MHCI MaSR CysA KaI6
Cap 1 00000 0 91434 0 72694 0 03555 0 78486 Capture 0 0002 0 0172 0 9223 0 0072
MHCI 0 91434 1 00000 0 73538 0 16379 0 78355 MHC-I 0 0002 0 0154 0 6512 0 0073
MaSR 0 72694 0 73538 1 00000 0 45348 0 86737
Macrophage scavenger receptor 0 0172 0 0154 0 1881 0 0012
CysA 0 03555 0 16379 0 45348 1 00000 0 29975 Cystatm A 0 9223 0 S512 0 1881 0 4001
KaI6 0 78486 0 78355 0 86737 0 29975 1 00000 Kallikrem S 0 0072 0 0073 0 0012 0 4001
AIpS 0 78187 0 83427 0 88609 0 45560 0 73854
Alpha synuclem 0 0075 0 0027 0 0006 0 1858 0 0147
Onctm 0 70996 0 57386 0 48744 0 39636 0 45550 Osteonectin 0 0214 0 0828 0 1530 0 2568 0 1859
01cm 0 89045 0 86870 0 88859 0 37656 0 88636 Osteocalcin 0 0006 0 0011 0 0006 0 2835 0 0006
TroC 0 43436 0 31430 0 47835 0 64809 0 58499 Troponin C 0 2097 0 3764 0 1620 0 0427 0 0757
AbT -0 22819 0 28518 -0 56752 -0 30728 -0 66100
Abeam Transglutaminase 2 0 5260 0 4245 0 0870 0 3878 0 0374
PGRP 0 97503 0 94115 0 79501 0 10705 0 87024
PGRP-I Beeta < 0001 < 0001 0 0060 0 7685 0 0011
PSA 0 38693 0 38415 0 22525 0 24452 0 05800 PSA 0 2693 0 2731 0 5315 0 4960 0 8736
Bab 0 58722 0 71291 0 69512 0 32085 0 78473
Labvision Tgase 2 0 0743 0 0207 0 0257 0 3660 0 0072
Aqua 0 95162 0 97871 0 79088 0 14776 0 85849 Aquaponn-4 < 0001 < 0001 0 0064 0 6837 0 0015
Capture Time DATA Summary table of Aqua by Disease 53 Disease=Prostati - -
The CORR Procedure
Pearson Correlation Coefficients, N = 10 Prob > |r| under HO Rho=0
AIpS Onctm 01cm TroC AbT
Cap 0 78187 0 70996 0 89045 0 43436 -0 22819
Capture 0 0075 0 0214 0 0006 0 2097 0 5260
MHCI 0 83427 0 57386 0 86870 0 31430 -0 28518
MHC-I 0 0027 0 0828 0 0011 0 3764 0 4245
MaSR 0 88S09 0 48744 0 88859 0 47835 -0 56752
Macrophage scavenger receptor 0 0006 0 1530 0 0006 0 1620 0 0870
CysA 0 45560 0 39636 0 37656 0 64809 -0 30728
Cystatm A 0 1858 0 2568 0 2835 0 0427 0 3878
KaI6 0 73854 0 45550 0 88636 0 58499 -0 66100
Kallikrem 6 0 0147 0 1859 0 0006 0 0757 0 0374
AIpS 1 00000 0 61101 0 93571 0 44771 -0 25825
Alpha synuclem 0 0606 < 0001 0 1945 0 4713
Onctm 0 61101 1 00000 0 68591 0 70842 0 16024
Osteonectin 0 0606 0 0285 0 0218 0 6583
01cm 0 93571 0 68591 1 00000 0 59115 -0 35623
Osteocalcin < 0001 0 0285 0 0719 0 3123
TroC 0 44771 0 70842 0 59115 1 00000 -0 32611 Troponin C 0.1945 0.0218 0.0719 0.3578
AbT 0.25825 0.16024 -0.35623 -0.32611 1.00000
Abeam Transglutaminase 2 0.4713 0.6583 0.3123 0.3578
PGHP 0.78471 0.62351 0.89608 0.44221 -0.41191
PGRP-I Beeta 0.0072 0.0541 0.0004 0.2007 0.2369
PSA 0.59808 0.65048 0.46557 0.25207 0.57498 PSA 0.0678 0.0417 0.1751 0.4823 0.0821
Lab 0.77545 0.35711 0.80455 0.39314 -0.27253
Labvision Tgase 2 0.0084 0.3111 0.0050 0.2610 0.4462
Aqua 0.81176 0.58657 0.89310 0.39068 -0.40354 Aquaporin-4 0.0043 0.0747 0.0005 0.2643 0.2475
Capture Time DATA: Summary table of Aqua by Disease 54 Disease=Prostati
The CORR Procedure
Pearson Correlation Coefficients, N = 10 Prob > |r| under HO: RhO=O
PGRP PSA Lab Aqua
Cap 0.97503 0.38693 0.58722 0.95162
Capture <.0001 0.2693 0.0743 <.0001
MHCI 0.94115 0.38415 0.71291 0.97871
MHC-I <.oooi 0.2731 0.0207 <.0001
MaSR 0.79501 0.22525 0.69512 0.79088
Macrophage scavenger receptor 0.0060 0.5315 0.0257 0.0064
CysA 0.10705 0.24452 0.32085 0.14776
Cystatin A 0.7685 0.4960 0.3660 0.6837
KaI6 0.87024 0.05800 0.78473 0.85849
Kallikrein 6 0.0011 0.8736 0.0072 0.0015
AIpS 0.78471 ' 0.59808 0.77545 0.81176
Alpha synuclein 0.0072 0.0678 0.0084 0.0043
Onctin 0.62351 0.65048 0.35711 0.58657
Osteonectin 0.0541 0.0417 0.3111 0.0747
Olcin 0.89608 0.46557 0.80455 0.89310
Osteocalcin 0.0004 0.1751 0.0050 0.0005
TroC 0.44221 0.25207 0.39314 0.39068
Troponin C 0.2007 0.4823 0.2610 0.2643
AbT -0.41191 0.57498 -0.27253 -0.40354
Abeam Transglutaminase 2 0.2369 0.0821 0.4462 0.2475
PGRP 1.00000 0.24166 0.62520 0.98838
PGRP-I Beeta 0.5012 0.0532 <.0001
PSA 0.24166 1.00000 0.42169 0.26843
PSA 0.5012 0.2248 0.4533
Lab 0.62520 0.42169 1.00000 0.67312
Labvision Tgase 2 0.0532 0.2248 0.0329
Aqua 0.98838 0.26843 0.67312 1.00000
Aquaporin-4 <.0001 0.4533 0.0329
Comparison in CaDture for Cstitis and KidSton 55
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Ξtd Dev Std Dev Std Dev Std Err
Cap Cstitis 10 167.42 256.01 344. 59 85 .175 123 .83 226 .07 39.158
Cap KidSton 10 82.852 95.161 107. 47 11 .836 17. 207 31. 413 5.4413
Cap Diff (1-2) 77.785 160.84 243 .9 66 .798 88. 402 130 .73 39.535 T-Tests
Variable Method Variances DF t Value Pr |t|
Cap Pooled Equal 18 4.07 0.0007
Cap Satterthwaite Unequal 9 35 4.07 0.0026
Equality of Variances
Variable Method NUm DF Den DF F Value Pr > F
Cap Folded F 9 9 51 79 <.0001
Comparison xn Capture for Cstitis and Endoaden 56
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Cstitis 10 167 42 256.01 344.59 85.175 123.83 226.07 39.158
Cap Endoaden 10 225. 29 360.44 495.59 129.95 188.93 344.91 59.745
Cap Diff (1-2) -254 .5 -104.4 45.642 120.7 159.73 236.22 71.434
T-Tests
Variable Method Variances t Value Pr > |t|
Cap Pooled Equal 18 -1.46 0.1610 Cap Satterthwaite Unequal 15.5 -1.46 0.1637
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 2.33 0.2241
Comparison m Capture for Cstitis and Prostate
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Cstitis 10 167.42 256.01 344.59 85.175 123.83 226.07 39.158 Cap Prostate 10 3.5322 7.2958 11.059 3.6188 5.2611 9.6047 1.6637 Cap Diff (1-2) 166.37 248.71 331.05 66.222 87.64 129.6 39.194
T-Tests
Variable Method Variances DF t Value Pr > |t|
Cap Pooled Equal 18 6.35 <.0001 Cap Satterthwaite Unequal 9.03 S.35 0.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 553.98 <.0001
Comparison in Capture for Cstitis and Prostati 58
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Cstitis 10 167.42 256.01 344. .59 85, .175 123 .83 226 .07 39 .158 Cap Prostati 10 429.47 521.09 612..71 88..095 128.08 233.82 40.501 Cap Diff (1-2) -383.4 -265.1 -14«5.7 95.,185 125.97 186.29 56.336 T-Tests
Variable Method Variances DF t Value Pr > |t|
Cap Pooled Equal 18 -4 71 0 .0002 Cap Satterthwaite Unequal 18 -4.71 0.0002
Equality of Variances
Variable Method Nutn DF Den DF F Value Pr > F
Cap Folded F 9 9 1.07 0.9216
Comparison in Capture for Cstitis and Arthπti
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Arthπti 10 197.8 273.45 349 .09 72 .737 105 .75 193.05 33 .44 Cap Cstitis 10 167.42 256.01 344.59 85.175 123.83 226.07 39.158 Cap Diff (1-2) -90.74 17.441 125.63 87.004 115 .14 170.28 51.494
T-Tests
Variable Method Variances DF t Value Pr > |t|
Cap Pooled Equal 18 0 .34 0 .7388 Cap Satterthwaite Unequal 17.6 0 .34 0.7388
Equality of Variances
Variable Method Nutn DF Den DF F Value Pr > F
Cap Folded F 9 9 1.37 0.6457
Comparison m Capture for Cstitis and Aortic 60
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Aortic 10 152.25 193.36 234.46 39. .525 57. 462 104.9 18. 171 Cap Cstitis 10 167.42 256.01 344.59 85,.175 123.83 226.07 39.158 Cap Diff (1-2) -153.3 -62.65 28.048 72..939 96.529 142.75 43.169
T-Tests
Variable Method Variances DF t Value Pr > |t|
Cap Pooled Equal 18 -1.45 0.1639 Cap Satterthwaite Unequal 12.7 -1.45 0.1710
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 4.64 0.0319
Comparison m Capture for Cstitis and Parkmso 61
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Cstitis 10 167.42 256.01 344.59 85.175 123.83 226.07 39.158 Cap Parkmso 10 137.34 140.77 144.2 3.2955 4.7911 8.7467 1.5151 Cap Diff (1-2) 32.907 115.24 197.57 66.212 87.626 129.58 39.188 T-Tests
Variable Method Variances DF t Value Pr > |t|
Cap Pooled Equal 18 2.94 0.0087 Cap Satterthwaite unequal 9.03 2.94 0.0164
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
Cap Folded F 9 9 668.00 <.0001
Comparison in Capture for KidSton and Endoaden 62
The TTEST Procedure Statistics
Lower CL Dpper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Endoaden 10 225 .29 360.44 49S .59 129 .95 188 .93 344.91 59.745 Cap KidSton 10 82.1352 95 161 107.47 11.836 17.207 31.413 5.4413 Cap Diff (1-2) 139.24 265.28 391.32 101.36 134 .15 198.38 59.992
T-Tests
Variable Method Variances DF t Value
Cap Pooled Equal 18 4.42 0.0003 Cap Satterthwaite Unequal 9 .15 4.42 0.0016
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 120 56 <.0001
Comparison in Capture for KidSton and Prostate 63
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap KidSton 10 82.852 95.161 107.47 11.836 17.207 31.413 5.4413
Cap Prostate 10 3.5322 7.2958 11.059 3.6188 5.2611 9.6047 1.6637
Cap Diff (1-2) 75.911 87.865 99.819 9.6138 12.723 18.815 5.69
T-Tests
Variable Method Variances DF t Value Pr |t|
Cap Pooled Equal 18 15.44 <.0001 Cap Satterthwaite Unequal 10.7 15.44 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 10.70 0.0016
Comparison in Capture for KidSton and Prostati 64
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev std Dev Std Dev Std Err
Cap KidSton 10 82.852 95.161 107.47 11 .836 17. 207 31. 413 5. 4413 Cap Prostati 10 429.47 521.09 612.71 88 .095 128 .08 233 .82 40 .501 Cap Diff (1-2) -511.8 -425.9 -340.1 69 .045 91. 377 135 .13 40 .865 T-Tests
Variable Method Variances DF t Value Pr > |t|
Cap Pooled Equal 18 -10 42 <.0001 Cap Satterthwaite Unequal 9.32 -10 42 <.0001
Equality of Variances
Variable Method Nura DF Den DP F Value Pr =■ F
Cap Folded F 9 9 55.40 < 0001
Comparison in Capture for KidSton and Arthnti
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Arthnti 10 197.8 273.45 349 .09 72.737 1OS .75 193.05 33 .44 Cap KidSton 10 82.852 95.161 107 .47 11.836 17. 207 31.413 5.4413 Cap Diff (1-2) 107.11 178.29 249 .47 57.244 75. 758 112.03 33 .88
T-Tests
Variable Method Variances DF t Value Pr > |t|
Cap Pooled Equal 18 5. .26 < .0001 Cap Satterthwaite Unequal 9 .48 5 .26 0 .0004
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
Cap Folded F 9 9 37.77 <.0001
Comparison in Capture for KidSton and Aortic 66
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Aortic 10 152.25 193 .36 234 .46 39 .525 57 .462 104.9 18 .171 Cap KidSton 10 82.852 95.161 107.47 11.836 17.207 31.413 5.4413 Cap Diff (1-2) 58.347 98.198 138.05 32.049 42.415 62.724 18.968
T-Tests
Variable Method Variances DF t Value Pr > |t|
Cap Pooled Equal 18 5.18 < .0001 Cap Satterthwaite Unequal 10.6 5.18 0.0003
Equality o£ Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 11.15 0.0014
Comparison m Capture for KidSton and Parkmso 67
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap KidSton 10 82.852 95.161 107. 47 11 .836 17.207 31 .413 5 .4413 Cap Parkmso 10 137.34 140.77 144 .2 3. 2955 4.7911 8. 7467 1 .5151 Cap Diff (1-2) -57.47 -45.61 -33. 74 9. 5434 12.63 18 .678 5 .6483 T-Tests
Variable Method Variances DF t Value Pr > |t|
Cap Pooled Equal 18 -8.07 <.0001 Cap Satterthwaite unequal 10.4 -8.07 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 12.90 0.0008
Comparison in Capture for Endoaden and Prostate 68
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Endoaden 10 225.29 360.44 495.59 129.95 188.93 344.91 59.745 Cap Prostate 10 3.5322 7.2958 11.059 3.6188 5.2611 9.6047 1.6637 Cap Diff (1-2) 227.58 353.14 478.71 100.98 133.65 197.64 59.768
T-Tests
Variable Method Variances t Value Pr > |t|
Cap Pooled Equal 18 5.91 <.0001 Cap Satterthwaite Unequal 9.01 5.91 0.0002
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 1289.58 <.0001
Comparison in Capture for Endoaden and Prostati 69
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Endoaden 10 225.29 360.44 495 .59 129 .95 188. 93 344.91 59.745 Cap Prostati 10 429.47 521.09 612.71 88.095 128.08 233.82 40.501 Cap Diff (1-2) -312.3 -160.7 -9.011 121.95 161.4 238.68 72.179
T-Tests
Variable Method Variances DF t Value Pr > |t|
Cap Pooled Equal 18 -2.23 0.0390 Cap Satterthwaite Unequal 15.8 -2.23 0.0409
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 2.18 0.2623
Comparison in Capture for Endoaden and Arthriti
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev std Dev Std Err
Cap Arthriti 10 197.8 273.45 349 .09 72. 737 105. 75 193. 05 33 .44 Cap Endoaden 10 225.29 360.44 495 .59 129 .95 188. 93 344. 91 59. 745 Cap Diff (1-2) -230.8 -86.99 56 .85 115 .68 153 .1 226 .4 68. 467 T-Tests
Variable Method Variances DF t Value Pr >
Figure imgf000412_0001
Cap Pooled Equal 18 -1 27 0 2200 Cap Satterthwaite Unequal 14.1 -1.27 0 2244
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
Cap Folded F 9 9 3 19 0.0989
Comparison in Capture for Endoaden and Aortic
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Aortic 10 152.25 193.36 234. .46 39.525 57. 462 104.9 18 .171 Cap Endoaden 10 225.29 360.44 495..59 129.95 188.93 344.91 59.745 Cap Diff (1-2) -298.3 -167.1 -35..89 105.51 139.64 206.5 62.447
T-Tests
Variable Method Variances DF t Value Pr > |t|
Cap Pooled Equal 18 -2 .68 0.0154 Cap Satterthwaite Unequal 10.7 -2.68 0.0221
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
Cap Folded F 9 9 10.81 0.0015
Comparison in Capture for Endoaden and Parkmso
The TTEST Procedure Statistics
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Endoaden 10 225.29 360.44 495. .59 129.95 188. .93 344 91 59 .745
Cap Parkmso 10 137.34 140.77 144.2 3.2955 4.7911 8.7467 1. 5151
Cap Diff (1-2) 94.113 219.67 345. .23 100.98 133 .64 197.63 59 .764
T-Tests
Variable Method Variances DF t Value Pr > |t|
Cap Pooled Equal 18 3 .68 0 .0017
Cap Satterthwaite Unequal 9 .01 3 .68 0 .0051
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 1555.00 <.0001
Comparison m Capture for Prostate and Prostati
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Prostate 10 3.5322 7.2958 11.059 3.6188 5.2611 9.6047 1.6637 Cap Prostati 10 429.47 521.09 612.71 88.095 128.08 233.82 40.501 Cap Diff (1-2) -599 -513.8 -428.6 68.488 90.64 134.04 40.535 T-Tests
Variable Method Variances DF t Value Pr > |t|
Cap Pooled Equal 18 -12.68 <.0001 Cap Satterthwaite Unequal 9.03 -12.68 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr =. F
Cap Folded F 9 9 592.62 <.0001
Comparison in Capture for Prostate and Arthriti
The TTEST Procedure Statistics
Lower CJj Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Arthriti 10 197.8 273.45 349.09 72 .737 105.75 193.05 33.44 Cap Prostate 10 3.5322 7.2958 11.059 3.6188 5.2611 9.6047 1.6S37 Cap Diff (1-2) 195.81 266.15 336.49 56.571 74.867 110.72 33.482
T-Tests
Variable Method Variances DF t Value Pr > It
Cap Pooled Equal 18 7.95 <.0001 Cap Satterthwaite Unequal 9.04 7.95 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 404.00 <.0001
Comparison in Capture for Prostate and Aortic 75
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Aortic 10 152.25 193.36 234.46 39.525 57 .462 104.9 18 .171 Cap Prostate 10 3.5322 7.2958 11.059 3.6188 5.2611 9.6047 1.SS37 Cap Diff (1-2) 147.73 186.06 224.4 30.83 40.802 60.339 18.247
T-Tests
Variable Method Variances DF t Value Pr » |t|
Cap Pooled Equal 18 10.20 < .0001 Cap Satterthwaite Unequal 9.15 10.20 < .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 119.29 <.0001
Comparison in Capture for Prostate and Parkinso 76
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev std Err
Cap Parkinso 10 137.34 140.77 144.2 3.2955 4.7911 8.7467 1.5151
Cap Prostate 10 3.5322 7.2958 11.059 3.6188 5.2611 9.6047 1.6637
Cap Diff (1-2) 128.74 133.47 138.2 3.8019 5.0316 7.4409 2.2502 T-Tests
Variable Method Variances DF t Value Pr > |t|
Cap Pooled Equal 18 59 .32 < .0001 Cap Satterthwaite Unequal 17.8 59.32 < .0001
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
Cap Folded F 9 9 1.21 0.7850
Comparison in Capture for Prostati and Arthriti
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Arthriti 10 197.8 273.45 349.09 72.737 105.75 193.05 33.44
Cap Prostati 10 429.47 521.09 612.71 88.095 128.08 233.82 40.501
Cap Diff (1-2) -358 -247.6 -137.3 88.742 117.44 173.68 52.522
T-Tests
Variable Method Variances t Value Pr > |t|
Cap Pooled Equal 18 -4.72 0.0002 Cap Satterthwaite Unequal 17.4 -4.72 0.0002
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
Cap Folded F 9 9 1.47 0.5773
Comparison in Capture for Prostati and Aortic 78
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean std Dev Std Dev std Dev Std Err
Cap Aortic 10 152.25 193.36 234. 46 39 .525 57. 462 104.9 18 .171
Cap Prostati 10 429.47 521.09 612. 71 88 .095 128 .08 233.82 40 .501
Cap Diff (1-2) -421 -327.7 -234 .5 75 .002 99 .26 146.79 44 .391
T-Tests
Variable Method Variances DF t Value Pr > |t|
Cap Pooled Equal 18 -7.38 < .0001
Cap Satterthwaite Unequal 12.5 -7.38 < .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 4.97 0.0256
Comparison m Capture for Prostati and Parkmso 79
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev std Dev Std Dev Std Err
Cap Parkmso 10 137.34 140.77 144.2 3. 2955 4.7911 8.7467 1. 5151 Cap Prostati 10 429.47 521.09 612.71 88 .095 128.08 233.82 40 .501 Cap Diff (1-2) -465.5 -380.3 -295.2 68 .479 90.626 134.02 40 .529 T-Tests
Variable Method Variances DF t Value Pr > |t
Cap Pooled Equal 18 -9.38 ■=.0001 Cap Satterthwaite Unequal 9.03 -9.38 <.0001
Equality of Variances
Variable Method Num DF Den DP F Value Pr > F
Cap Folded F 9 9 714.59 <.0001
Comparison in Capture for Arthriti and Aortic
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Aortic 10 152.25 193.36 234.46 39.525 57.462 104.9 18.171
Cap Arthriti 10 197.8 273.45 349.09 72.737 105.73 193.05 33.44
Cap Diff (1-2) -160 -80.09 -0.13 64.303 85.101 125.85 38.058
T-Tests
Variable Method Variances t Value Pr > |t|
Cap Pooled Equal 18 -2.10 0.0497 Cap Satterthwaite Unequal 13.9 -2.10 0.0541
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 3.39 0.0836
Comparison in Capture for Arthriti and Parkinso
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Arthriti 10 197.8 273.45 349.09 72.737 105.75 193.05 33.44 Cap Parkinso 10 137.34 140.77 144.2 3.2955 4.7911 8.7467 1.5151 Cap Diff (1-2) 62.351 132.68 203.01 56.559 74.851 110.69 33.475
T-Tests
Variable Method Variances DF t Value
Cap Pooled Equal 18 3 .96 0.0009 Cap Satterthwaite Unequal 9.04 3.96 0.0033
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 487.15 <.0001
Comparison in Capture for Aortic and Parkinso 82
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Cap Aortic 10 152 .25 193 .36 234.46 39 .525 57 .462 104.9 18.171
Cap Parkinso 10 137 .34 140 .77 144.2 3. 2955 4. 7911 8.7467 1.5151
Cap Diff (1-2) 14. 282 52. 591 90.899 30 .809 40 .773 60.296 18.234 T-Tests
Variable Method Variances DF t Value Pr > ItI
Cap Pooled Equal 18 2.88 0 .0099 Cap Satterthwaite Unequal 9.13 2.88 0.0178
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Cap Folded F 9 9 143-84 <.0001
Comparison in MHC-I for Cstitis and KidSton
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev std Dev Std Dev Std Err
MHCI Cstitis 10 135.19 329.35 523.51 186.69 271.41 495.49 85.828
MHCI KidSton 10 35.585 41.844 48.103 6.0181 8.7493 15.973 2.7668
MHCI Diff (1-2) 107.1 287.51 467.92 145.09 192.02 283.96 85.872
T-Tests
Variable Method Variances t Value Pr lt|
MHCI Pooled Equal 18 3.35 0.0036 MHCI Satterthwaite Unequal 9.02 3.35 0.0085
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 962.30 <.0001
Comparison in MHC-I for Cstitis and Endoaden
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Cstitis 10 135.19 329.35 523 .51 186 .69 271.41 495.49 85. 828
MHCI Endoaden 10 319.04 512.03 705 .02 185. .57 269.78 492.52 85. 313
MHCI Diff (1-2) -436.9 -182.7 71.564 204, .47 270.6 400.17 121 .02
T-Tests
Variable Method Variances DF t ' Value Pr > |t|
MHCI Pooled Equal 18 -1.51 0.1485
MHCI Satterthwaite Unequal 18 -1.51 0.1485
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 1.01 0.9860
Comparison in MHC-I for Cstitis and Prostate
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Cstitis 10 135.19 329.35 523.51 186.69 271.41 495.49 85.828
MHCI Prostate 10 0.1451 0.3769 0.6087 0.2229 0.3241 0.5916 0.1025
MHCI Diff (1-2) 148.66 328.97 509.29 145.01 191.92 283.81 85.828 T-Tests
Variable Method Variances DF t Value Pr > |t]
MHCI Pooled Equal 18 3.83 0.0012
MHCI Satterthwaite Unequal 9 3.83 0.0040
Equality of Variances
Variable Method Num DP Den DF F Value Pr > F
MHCI Folded F 9 9 701503 < 0001
Comparison in MHC-I for Ostitis and Prostati 86
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev std Err
MHCI Cstltis 10 135. 19 329.35 523.51 186.69 271.41 495.49 85.828 MHCI Prostati 10 326. 17 468.36 610.54 136.71 198.76 362.86 62.853 MHCI Diff (1-2) -362 .5 -139 84.493 179.74 237.87 351.78 106.38
T-Tests
Variable Method Variances DF t Value Pr > |t|
MHCI Pooled Equal 18 -1.31 0.2078 MHCI Satterthwaite Unequal 16.5 -1.31 0.2092
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 1.86 0.3670
Comparison m MHC-I for Cstitis and Arthriti
The TTEST Procedure Statistics
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Arthriti 10 241.19 433.06 624. .94 184.49 268 .22 489.67 84. 819
MHCI Cstitis 10 135.19 329.35 523. .51 186.69 271 .41 495.49 85. 828
MHCI Diff (1-2) -149.8 103.71 357. .23 203.88 269 .82 399.02 120 .67
T-Tests
Variable Method Variances DF t Value Pr > ItI
MHCI Pooled Equal 18 0.86 0 .4014
MHCI Satterthwaite Unequal 18 0.86 0 .4014
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 1.02 0.9725
Comparison in MHC-I for Cstitis and Aortic 88
The TTEST Procedure
Statistics
Lower CL Upper CL jower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Aortic 10 188.76 316.52 444.27 122.84 178.59 326.04 56.475
MHCI Cstitis 10 135.19 329.35 523.51 186.69 271.41 495.49 B5.828
MHCI Diff (1-2) -228.7 -12.83 203.02 173.59 229.74 339.74 102.74 T-Tests
Variable Method Variances DF t Value Pr > It]
MHCI Pooled Equal 18 -0 12 0. 9020
MHCI Satterthwaite Unequal 15.6 -0.12 0. 9022
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 2.31 0.2283
Comparison m MHC-I for Cstitis and Parkmso 89
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Cstitis 10 135.19 329.35 523.51 186. .69 271. .41 495.49 85 .828
MHCI Parkmso 10 73.558 75.278 76.998 1.6536 2.4041 4.389 0. 7603
MHCI Diff (1-2) 73.748 254.07 434.4 145 .02 191. .92 283.82 85 .831
T-Tests
Variable Method Variances DF t Value Pr >
Figure imgf000418_0001
MHCI Pooled Equal 18 2.96 0 .0084
MHCI Satterthwaite Unequal 9 2.96 0 .0160
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 12745.0 <.0001
Comparison m MHC-I for KidSton and Endoaden 90
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean std Dev Std Dev Std Dev Std Err
MHCI Endoaden 10 319 .04 512 .03 705 .02 185 .57 269.78 492.52 85.313
MHCI KidSton 10 35. 585 41. 844 48. 103 6.0181 8.7493 15.973 2.7668
MHCI Diff (1-2) 290 .86 470 .19 649 .52 144. .22 190.87 282.26 85.358
T-Tests
Variable Method Variances DF t Value Pr > | t |
MHCI Pooled Equal 18 5.51 <.0001 MHCI Satterthwaite Unequal 9.02 5.51 0.0004
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 950.79 <.0001
Comparison in MHC-I for KidSton and Prostate 91
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI KidSton 10 35.585 41 .844 48.103 6 .0181 8 .7493 15.973 2.7668
MHCI Prostate 10 0.1451 0. 3769 0.6087 0 .2229 0 .3241 0.5916 0.1025
MHCI Diff (1-2) 35.65 41 .467 47.284 4 .6779 6 .1909 9.1553 2.7687 T-Tests
Variable Method Variances DP t Value Pr > |t|
MHCI Pooled Equal 18 14.98 <.0001
MHCI Satterthwaite Unequal 9.02 14.98 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 728.99 <.0001
Comparison in MHC-I for KidSton and Prostati 92
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Ston 10 35.585 41.844 48.103 S.0181 8.7493 15.973 2.7668 MHCI stati 10 326.17 468.36 610.54 136.71 198 .76 3S2.86 62.853 MHCI f (1-2) -558.7 -426.5 -294.3 106.3 140 .68 208.04 62.914
T-Tests
Variable Method Variances DF t Value Pr > |t|
MHCI Pooled Equal 18 -6.78 <.0001
MHCI Satterthwaite Unequal 9 .03 -6.78 <-0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 516.07 <.0001
Comparison m MHC-I for KidSton and Arthπti 93
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI hπti 10 241 .19 433.06 624 .94 184 .49 268.22 489.67 84 .819 MHCI Ston 10 35.585 41.844 48. 103 6.0181 8.7493 15.973 2. 7668 MHCI f (1-2) 212 .93 391.22 569 .51 143 .39 189.76 280.62 84 .864
T-Tests
Variable Method Variances DF t Value Pr >
Figure imgf000419_0001
MHCI Pooled Equal 18 4.61 0 .0002
MHCI Satterthwaite Unequal 9 .02 4.61 0 .0013
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 939.80 <.0001
Comparison in MHC-I for KidSton and Aortic
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Aortic 10 188 .76 316 .52 444 .27 122.84 178.59 326 .04 S6 .475
MHCI KidSton 10 35. 585 41. 844 48. 103 6.0181 8.7493 15. 973 2. 7668
MHCI Diff (1-2) 155 .88 274 .67 393 .47 95.535 126.43 186 .97 56 .543 T-Tests
Variable Method Variances DF t Value Pr > |t|
MHCI Pooled Equal 18 4.86 0. 0001
MHCI Satterthwaite Unequal 9.04 4.86 0 0009
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 416 65 <.0001
Comparison m MHC-I for KidSton and Parkmso 95
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI KidSton 10 35.585 41. 844 48.103 6.0181 8.7493 15.973 2.7668
MHCI Parkmso 10 73.558 75. 278 76.998 1.6536 2.4041 4.389 0.7603
MHCI Diff (1-2) -39.46 -33 .43 -27.41 4.848 6.416 9.4881 2.8693
T-Tests
Variable Method Variances t Value Pr > |t|
MHCI Pooled Equal 18 -11.65 <.0001 MHCI Satterthwaite Unequal 10.4 -11.65 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 13.24 0.0007
Comparison in MHC-I for Endoaden and Prostate 96
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Endoaden 10 319.04 512 03 705.02 185.57 269.78 492.52 85.313 MHCI Prostate 10 0.1451 0.3769 0.6087 0.2229 0.3241 0.5916 0.1025 MHCI Diff (1-2) 332.42 511.65 690.89 144.14 190.77 282.11 85.313
T-Tests
Variable Method Variances DF t Value Pr |t|
MHCI Pooled Equal 18 6.00 <.0001 MHCI Satterthwaite Unequal 9 6.00 0.0002
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 693112 <.0001
Comparison m MHC-I for Endoaden and Prostati 97
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Endoaden 10 319.04 512 .03 705. 02 185 .57 269 .78 492. 52 85. 313
MHCI Prostati 10 326.17 468.36 610. 54 136 .71 198 .76 362. 86 62. 853
MHCI Diff (1-2) -179 43 .675 266 .3 179 .04 236 .95 350 .4 105 .97 T-Tests
Variable Method Variances DF t Value Pr > |t|
MHCI Pooled Equal 18 0.41 0.6851 MHCI Satterthwaite Unequal 16 5 0.41 0.6855
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 1.84 0.3762
Comparison in MHC-I for Endoaden and Arthπti 98
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Arthπti 10 241. 19 433 .06 624.94 184.49 268.22 489.67 84.819
MHCI Endoaden 10 319. 04 512 .03 705.02 185.57 269.78 492.52 85.313
MHCI Diff (1-2) -331 .7 -78 .97 173.78 203.26 269 397.81 120.3
T-Tests
Variable Method Variances t Value Pr > |t|
MHCI Pooled Equal 18 -0.66 0.5199 MHCI Satterthwaite Unequal 18 -0.66 0.5199
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 1.01 0.9865
Comparison in MHC-I for Endoaden and Aortic
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Aortic 10 188.76 316.52 444.27 122 .84 178 .59 326.04 56.475
MHCI Endoaden 10 319.04 512.03 705.02 185 .57 269 .78 492.52 85.313
MHCI Diff (1-2) -410.5 -195.5 19.436 172 .87 228 .78 338.32 102.31
T-TeStS
Variable Method Variances DF t Value Pr > |t|
MHCI Pooled Equal 18 -1.91 0.0721
MHCI Satterthwaite Unequal 15.6 -1.91 0.0745
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 2.28 0.2349
Comparison in MHC-I for Endoaden and Parkinso 100
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Endoaden 10 319.04 512.03 705.02 185.57 269.78 492 .52 85.313
MHCI Parkinso 10 73.558 75.278 76.998 1.6536 2.4041 4.389 0.7603
MHCI Diff (1-2) 257.51 436.75 616 144.15 190.77 282 .12 85.316 T-Tests
Variable Method Variances DF t Value Pr > |t|
MHCI Pooled Equal 18 5.12 <.0001
MHCI Satterthwaite Unequal 9 5.12 0.0006
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 12592.5 <.0001
Comparison in MHC-I for Prostate and Prostatl 101
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Prostate 10 0 1451 0.3769 0.6087 0.2229 0.3241 0.5916 0.1025
MHCI Prostatl 10 326.17 468.36 610.54 136.71 198.76 362.86 62.853
MHCI Dlff (1-2) -600 -468 -335.9 106.2 140.54 207.84 62.853
T-Tests
Variable Method Variances DF t Value Pr > |t|
MHCI Pooled Equal 18 -7.45 ■c.OOOl MHCI Satterthwaite Unequal 9 -7.45 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 376207 <.0001
Comparison m MHC-I for Prostate and Arthriti
The TTEST Procedure Statistics
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Arthriti 10 241.19 433.06 624.94 184.49 268.22 489.67 84 .819 MHCI Prostate 10 0 1451 0.3769 0.6087 0.2229 0.3241 0.5916 0. 1025 MHCI Diff (1-2) 254.49 432.69 610.88 143.31 189.56 280.47 84 .819
T-TestS
Variable Method Variances DF t Value Pr > |t|
MHCI Pooled Equal 18 5.10 < .0001
MHCI Satterthwaite Unequal 9 5.10 0 .0006
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 685104 <.0001
Comparison in MHC-I for Prostate and Aortic 103
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Aortic 10 188.76 316.52 444.27 122.84 178.59 326.04 56.475
MHCI Prostate 10 0.1451 0.3759 0.6087 0.2229 0.3241 0.5915 0.1025
MHCI Diff (1-2) 197.49 316.14 434.79 95.421 126.28 186.75 56.475 T-Tests
Variable Method Variances DF t Value Pr > |t|
MHCI Pooled Equal 18 5.S0 < 0001 MHCI Satterthwaite Unequal 9 5 60 0.0003
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F MHCI Folded F 9 9 303731 <.0001
Comparison m MHC-I for Prostate and Parkmso 104
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Parkmso 10 73.5S8 75.278 76 .998 1 .6536 2.4041 4.389 0 .7603
MHCI Prostate 10 0.14S1 0.3769 0. 6087 0 .2229 0.3241 0.5916 0 .1025
MHCI Diff (1-2) 73.29 74.901 76 .513 1 .2961 1.7154 2.5367 0 .7671
T-Tests
Variable Method Variances DF t Value Pr > |t|
MHCI Pooled Equal 18 97. .64 < .0001
MHCI Satterthwaite Unequal 9 .33 97 .64 < .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 55.04 <.0001
Comparison in MHC-I for Prostati and Arthnti 105
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Arthπti 10 241.19 433.06 624.94 184 .49 268 .22 489.67 84. 819
MHCI Prostati 10 326.17 468.36 610.54 136, .71 198 .76 362.86 62. 853
MHCI Diff (1-2) -257.1 -35.29 186.5 178. .37 236 .06 349.09 105 .57
T-Tests
Variable Method Variances DF t Value Pr > |t|
MHCI Pooled Equal 18 -0 .33 0.7420
MHCI Satterthwaite Unequal 16.6 -0. .33 0.7423
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F MHCI Folded F 9 9 1.82 0.3852
Comparison in MHC-I for Prostati and Aortic 1
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std : Dev Std Dev Std Err
MHCI Aortic 10 188.76 316.52 444.27 122 .84 178 .59 326.04 56.475
MHCI Prostati 10 326.17 468.36 610.54 136 .71 198 .76 362.86 62.853
MHCI Diff (1-2) -329.4 -151.8 2S.686 142 .77 188 .94 279.41 84.498 T-Tests
Variable Method Variances DF t Value Pr > ]t|
MHCI Pooled Equal 18 -1 80 0.0891 MHCI Satterthwaite Unequal 17.8 -1.80 0.0893
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 1.24 0 7551
Comparison in MHC-I for Prostati and Parkmso 107
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev std Dev Std Dev Std Err
MHCI Parkmso 10 73.558 75.278 76.998 1.6536 2.4041 4.389 0.7603
MHCI Prostati 10 326.17 468.36 610.54 136.71 198.76 362.86 62.853
MHCI Diff (1-2) -525.1 -393.1 -261 106.2 140.55 207.85 62.858
T-Tests
Variable Method Variances DF t Value Pr > |t|
MHCI Pooled Equal 18 -6.25 ■c.OOOl MHCI Satterthwaite Unequal 9 -6.25 0.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 6834.95 <.0001
Comparison m MHC-I for Arthriti and Aortic 108
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Aortic 10 188.76 316.52 444.27 122.84 178.59 326.04 56.475
MHCI Arthriti 10 241.19 433.06 624.94 184.49 268.22 489.67 84.819
MHCI Dlff (1-2) -330.6 -116.5 97.538 172.17 227.86 336.96 101.9
T-Tests
Variable Method Variances DF t Value Pr >
MHCI Pooled Equal 18 -1.14 0.2677 MHCI Satterthwaite Unequal 15.7 -1.14 0.2699
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 2.26 0.2414
Comparison m MHC-I for Arthriti and Parkmso 109
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Arthriti 10 241 .19 433.06 624.94 184.49 268 .22 489.67 84 .819
MHCI Parkmso 10 73.558 75.278 76.998 1.6536 2.4041 4.389 0. 7603
MHCI Dlff (1-2) 179. .58 357.79 535.99 143.32 189. .67 280.49 84 .822 T-Tests
Variable Method Variances DF t Value Pr > |t]
MHCI Pooled Equal 18 4.22 0.0005 MHCI Satterthwaite Unequal 9 4.22 0.0022
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 12447.0 <.0001
Comparison in MHC-I for Aortic and Parkinso
The TTEST Procedure Statistics
Lower CIi Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MHCI Aortic 10 188.76 316.52 444.27 122.84 178.59 326.04 56.475 MHCI Parkinso 10 73.558 75.278 76.998 1.653S 2.4041 4.389 0.7603 MHCI Diff (1-2) 122.58 241.24 359.9 95.429 126.29 186.77 56.48
T-Tests
Variable Method Variances DF t Value Pr > |t|
MHCI Pooled Equal 18 4.27 0.0005 MHCI Satterthwaite Unequal 9 4.27 0.0021
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MHCI Folded F 9 9 5518.21 <.0001
Comparison in Macrophage scavenger receptor for Cstitis and Kidston 111
The TTEST Procedure Statistics
Lower CB Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Cstitis 10 75.537 158.91 242.27 80 .161 116.54 212.76 36 .854 MaSR KidSton 10 33.431 38.401 43.371 4.7787 6.9475 12.683 2.197 MaSR Diff (1-2) 42.941 120.51 198.07 62.379 82.554 122.08 36.919
T-Tests
Variable Method Variances DF t Value Pr > |t)
MaSR Pooled Equal 18 3.26 0.0043 MaSR Satterthwaite Unequal 9.06 3.26 0.0097
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 281.39 <.0001
Comparison in Macrophage scavenger receptor for Cstitis and Endoaden 112
The TTEST Procedure Statistics
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Cstitis 10 75 .537 158.91 242.27 80.161 116 .54 212 .76 36.854
MaSR Endoaden 10 28 .238 41.541 S4.844 12.791 18. 596 33. 949 5.8806
MaSR Diff (1-2) 38 .959 117.37 195.77 63.056 83 .45 123 .41 37.32 T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 18 3.14 0. 0056
MaSR Satterthwaite Unequal 9.46 3.14 0. 0111
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 39 28 <.0001
Comparison in Macrophage scavenger receptor for Cstitis and Prostate 113
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev std Dev Std Dev Std Err
MaSR Cstitis 10 75.537 158.91 242.27 80.161 116.54 212.76 36.854
MaSR Prostate 9 10.896 12.9 14.905 1.7614 2.6077 4.9957 0.8692
MaSR Diff (1-2) 63.786 146.01 228.23 63.644 84.81S 127.15 38.97
T-Tests
Variable Method Variances DF t Value Pr > ]t|
MaSR Pooled Equal 17 3.75 0 0016 MaSR Satterthwaite Unequal 9.01 3.96 0.0033
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 8 1997.33 <.0001
Comparison m Macrophage scavenger receptor for Cstitis and Prostati 114
The TTEST Procedure Statistics
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Cstitis 10 75.537 158.91 242 .27 80 .161 116 .54 212.76 36 .854
MaSR Prostati 10 18.653 25.425 32. 197 6. 5113 9.4664 17.282 2. 9935
MaSR Diff (1-2) 55.8 133.48 211 .16 62 .473 82. 679 122.27 36 .975
T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 18 3.61 0 .0020
MaSR Satterthwaite Unequal 9 .12 3.61 0 .0055
Equality of Variances
Variable Method Mum DF Den DF F Value Pr > F
MaSR Folded F 9 9 151.56 <.0001
Comparison in Macrophage scavenger receptor for Cstitis and Arthriti 115
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Arthriti 10 159.38 215.19 271 53 .663 78. .018 142 .43 24. 671
MaSR Cstitis 10 75.537 158.91 242.27 80 .161 116.54 212 .76 36. 854
MaSR Diff (1-2) -36.89 56.28 149.45 74. .933 99. .168 146. .65 44. 349 T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 18 1.27 0.2206
MaSR Satterthwaxte Unequal 15.7 1.27 0.2229
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 2 23 0.2476
Comparison in Macrophage scavenger receptor for Cstitis and Aortic HS
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Aortic 10 15.332 26.638 37.944 10.871 15 805 28.854 4.998
MaSR Cstitis 10 75.537 158.91 242.27 80.161 116.54 212.76 35.854
MaSR Dlff (1-2) -210.4 -132.3 -54.13 62.838 83.162 122.98 37.191
T-Tests
Variable Method Variances t Value Pr > |t|
MaSR Pooled Equal 18 -3.56 0.0023 MaSR Satterthwaite Unequal 9.33 -3.56 0.0058
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 54 37 <.0001
Comparison in Macrophage scavenger receptor for Cstitis and Parkmso 117
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Cstitis 10 75.537 158.91 242.27 80. .161 116.54 212.76 36 .854
MaSR Parkmso 10 19.551 20.936 22.321 1.3314 1.9357 3.5339 0. 6121
MaSR Diff (1-2) 60 533 137.97 215.41 62, .277 82. .419 121.88 36 .859
T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 18 3.74 0.0015
MaSR Satterthwaite Unequal 9 3.74 0.0046
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 3624.78 <.0001
Comparison m Macrophage scavenger receptor for KidSton and Endoaden 118
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev std Dev Std Dev Std Err
MaSR Endoaden 10 28.238 41.541 54 .844 12. .791 18 .596 33 .949 5.8806
MaSR KidSton 10 33.431 38.401 43 .371 4.7787 6. 9475 12 .683 2.197
MaSR Dlff (1-2) -10.05 3.1398 16 .329 10. .607 14 .037 20 .758 6.2776 T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 18 0.50 0 .6230 MaSR Satterthwaite Unequal 11.5 0.50 0.6264
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
MaSR Folded F 9 9 7.16 0.0072
Comparison in Macrophage scavenger receptor for KidSton and Prostate 119
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev std Dev Std Dev Std Err
MaSR KidSton 10 33 .431 38.401 43.371 4.7787 6.9475 12.683 2.197
MaSR Prostate 9 10 .896 12.9 14.905 1.7614 2.6077 4.9957 0.8692
MaSR Diff (1-2) 20 .302 25.5 30.699 4.0237 5.3622 8.0387 2.4638
T-Tests
Variable Method Variances t Value Pr > |t|
MaSR Pooled Equal 17 10.35 <.0001 MaSR Satterthwaite Unequal 11.7 10.79 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 8 7.10 0.0111
Comparison in Macrophage scavenger receptor for KidSton and Prostati
The TTEST Procedure Statistics
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR KidSton 10 33 .431 38 .401 43 .371 4.7787 6. 9475 12.683 2.197
MaSR Prostati 10 18. .653 25 .425 32 .197 6.5113 9. 4664 17.282 2.9935
MaSR Diff (1-2) 5. .175 12 .976 20 .777 6.2739 8 .303 12.279 3.7132
T-Tests
Variable Method Variances DF t Value Pr > It=I
MaSR Pooled Equal 18 3.49 0.0026
MaSR Satterthwaite Unequal 16.5 3.49 0.0029
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 1.86 0.3703
Comparison in Macrophage scavenger receptor for KidSton and Arthriti
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Arthriti 10 159 .38 215 .19 271 53.663 78.018 142.43 24.671
MaSR KidSton 10 33. 431 38. 401 43. 371 4.7787 6.9475 12.683 2.197
MaSR Diff (1-2) 124 .75 176 .79 228 .82 41.85 55.385 81.905 24.769 T-Tests
Variable Method Variances DF t Value Pr > ]t|
MaSR Pooled Equal 18 7 14 < 0001
MaSR Satterthwaite Unequal 9.14 7.14 <-0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 126 10 < 0001
Comparison in Macrophage scavenger receptor for KidSton and Aortic 122
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Aortic 10 15. 332 26. 638 37 944 10.871 15 805 28.854 4.998
MaSR KidSton 10 33. 431 38 401 43 371 4.7787 6 9475 12.683 2.197
MaSR Diff (1-2) -23 23 -11 .76 -0.293 9.2245 12.208 18.053 5.4596
T-Tests
Variable Method Variances t Value Pr > |t|
MaSR Pooled Equal 18 -2.15 0.0450 MaSR Satterthwaite Unequal 12.4 -2.15 0.0516
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 5 18 0.0224
Comparison m Macrophage scavenger receptor for KidSton and Parkmso 123
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Ston 10 33 431 38 .401 43 371 4 .7787 6.9475 12.683 2.197 MaSR kmso 10 19 551 20 .936 22 321 1 .3314 1.9357 3.5339 0 .6121 MaSR f (1-2) 12 .673 17 .465 22 .256 3 .8534 5.0997 7.5416 2 .2807
T-Tests
Variable Method Variances DF t Value Pr > It|
MaSR Pooled Equal 18 7.66 < .0001
MaSR Satterthwaite Unequal 10.4 7 66 < .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 12.88 0 0008
Comparison in Macrophage scavenger receptor for Endoaden and Prostate 124
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Endoaden 10 28. 238 41.541 54 .844 12 .791 18.596 33 .949 S .8806
MaSR Prostate 9 10. 896 12 9 14 .905 1. 7614 2.6077 4. 9957 0 .8692
MaSR Diff (1-2) 15 .41 28.64 41 .871 10 242 13.648 20 .461 6.271 T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 17 4.57 0.0003
MaSR Satterthwaite Unequal 9.39 4.82 o.oooa
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 8 50.85 c.OOOl
Comparison in Macrophage scavenger receptor for Endoaden and Prostati 125
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev std Dev Std Dev Std Err
MaSR Endoaden 10 28 .238 41 .541 54.844 12.791 18.596 33.949 5.8806 MaSR Prostati 10 18 .653 25.425 32.197 6.5113 9.4664 17.282 2.9935 MaSR Diff (1-2) 2. 2527 16 . HS 29.979 11.149 14.755 21.82 6.5987
T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 18 2 44 0.0251 MaSR Satterthwaite Unequal 13.4 2.44 0.0292
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 3.86 0.0569
Comparison m Macrophage scavenger receptor for Endoaden and Arthπti 126
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR hriti 10 159.38 215.19 271 53 .663 78 .018 142.43 24 .671 MaSR oaden 10 28.238 41.541 54. 844 12 .791 18 .596 33.949 5. 8806 MaSR f (1-2) 120.36 173.65 226 .93 42 .852 56 .712 83.867 25 .362
T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 18 6 85 < .0001
MaSR Satterthwaite Unequal 10 6.85 < .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 17.60 0.0002
Comparison in Macrophage scavenger receptor for Endoaden and Aortic 127
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Aortic 10 15.332 26.638 37 .944 10.871 15 .805 28. 854 4.998 MaSR Endoaden 10 28.238 41.541 54 .844 12.791 18 .596 33. 949 5 .8806 MaSR Diff (1-2) -31.12 -14.9 1. 3115 13.04 17 .257 25 .52 7 .7176 T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 18 -1 93 0 0694
MaSR Satterthwaite Unequal 17 5 -1.93 0 0S98
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 1.38 0 6359
Comparison in Macrophage scavenger receptor for Endoaden and Parkmso 128
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Endoaden 10 28 238 41 .541 54.844 12.791 18.596 33.949 5. 8806
MaSR Parkmso 10 19 551 20 .936 22.321 1.3314 1 9357 3 5339 0 6121
MaSR Diff (1-2) 8.1833 20 .605 33.026 9.9895 13.22 19.551 5. 9124
T-Tests
Variable Method Variances DP t Value Pr > |t|
MaSR Pooled Equal 18 3.49 0 0026
MaSR Satterthwaite Unequal 9.2 3.49 0 0067
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 92 29 <.0001
Comparison m Macrophage scavenger receptor for Prostate and Prostati 129
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Prostate 9 10.896 12 9 14.905 1 7614 2 6077 4.9957 0.8692
MaSR Prostati 10 18 653 25.425 32 197 6.5113 9.4664 17.282 2.9935
MaSR Diff (1-2) -19 42 -12.52 -5.626 5.34 7.1163 10 668 3.2697
T-Tests
Variable Method Variances t Value Pr > |t|
MaSR Pooled Equal 17 -3.83 0.0013 MaSR Satterthwaite Unequal 10.5 -4.02 0.0022
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 8 13.18 0.0013
Comparison m Macrophage scavenger receptor for Prostate and Arthriti 130
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Arthriti 10 159 .38 215. 19 271 53 .663 78 .018 142.43 24.671
MaSR Prostate 9 10. 896 12 .9 14. 905 1. 7614 2. 6077 4.9957 0.8692
MaSR Diff (1-2) 147 .23 202. 29 257 .34 42 .618 56 .794 85.143 26.095 T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 17 7.75 < oooi
MaSR Ξatterthwaite Unequal 9.02 8.19 <-0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 8 895.10 <.0001
Comparison in Macrophage scavenger receptor for Prostate and Aortic 131
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR tic 10 15 .332 26 .638 37. 944 10 .871 15 .805 28.854 4.998 MaSR state 9 10 .89S 12.9 14. 90S 1. 7614 2. 5077 4.9957 0 .8692 MaSR f (1-2) 2.4S57 13 .738 25 .02 8. 7331 11 .638 17.447 5 .3474
T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 17 2.57 0 .0199
MaSR Satterthwaite Unequal 9 .54 2.71 0 .0229
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 8 36.73 <.0001
Comparison m Macrophage scavenger receptor for Prostate and Parkinso
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Parkmso 10 19.551 20.936 22. 321 1 .3314 1.9357 3.5339 0. .6121
MaSR Prostate 9 10.896 12.9 14. 905 1 .7614 2.6077 4.9957 0, .8692
MaSR Diff (1-2) 5.8285 8.0356 10. 243 1 .7085 2.2768 3.4132 1. .0461
T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 17 7.68 <.oooi
MaSR Satterthwaite Unequal 14.7 7.56 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F MaSR Folded F 8 9 1.81 0.3927 Comparison m Macrophage scavenger receptor for Prostati and Arthπti 133
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Arthriti 10 159.38 215.19 271 53.663 78.018 142.43 24.671
MaSR Prostati 10 18.653 25.425 32.197 6.5113 9.4664 17.282 2.9935
MaSR Diff (1-2) 137.55 189.76 241.97 41.99 55.571 82.18 24.852 T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 18 7 64 ■=.0001 MaSR Satterthwaite Unequal 9.26 7.64 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 67.92 <.0001
Comparison m Macrophage scavenger receptor for Prostati and Aortic 134
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Aortic 10 15. 332 26 .638 37. 944 10 .871 15 .805 28.854 4 .998
MaSR Prostati 10 18. 653 25 .425 32. 197 6. 5113 9. 4664 17.282 2. 9935
MaSR Diff (1-2) -11 .03 1. 2134 13. 453 9. 8435 13 .027 19.265 5. 8259
T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 18 0.21 0 .8374
MaSR Satterthwaite Unequal 14.7 0.21 0 .8379
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 2.79 0.1427
Comparison in Macrophage scavenger receptor for Prostati and Parkmso 135
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Parkmso 10 19.551 20.936 22.321 1.3314 1.9357 3.5339 0.6121 MaSR Prostati 10 18.653 25.425 32.197 6.5113 9.4664 17.282 2.9935 MaSR Diff (1-2) -10.91 -4.489 1.9306 5.1625 6.8323 10.104 3.0555
T-Tests
Variable Method Variances t Value Pr > |t|
MaSR Pooled Equal 18 -1.47 0.1591
MaSR Satterthwaite Unequal 9.75 -1.47 0.1733
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 23.92 <.0001
Comparison in Macrophage scavenger receptor for Arthnti and Aortic 136
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Aortic 10 15.332 26.638 37.944 10 .871 15 .805 28. 854 4 .998 MaSR Arthnti 10 159.38 215 .19 271 53 .663 78 .018 142 .43 24 .671 MaSR Diff (1-2) -241.4 -188.5 -135.7 42 .531 56 .287 83. 239 25 .172 T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 18 -7.49 <.0001 MaSR Satterthwaite Unequal 9.74 -7.49 <.O001
Equality of Variances
Variable Method Nutn DF Den DF F Value Pr > F
MaSR Folded F 9 9 24.37 <-0001
Comparison in Macrophage scavenger receptor for Arthriti and Parkinso 137
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Arthriti 10 159.38 215.19 271 53.663 78 .018 142.43 24.671
MaSR Parkinso 10 19.551 20.935 22.321 1.3314 1. 9357 3.5339 0.6121
MaSR Diff (1-2) 142.4 194.25 246.1 41.697 55 .184 81.607 24.679
T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 18 7.87 <.0001
MaSR Satterthwaite Unequal 9 .01 7.87 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 1624.44 <.0001
Comparison in Macrophage scavenger receptor for Aortic and Parkinso 138
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
MaSR Aortic 10 15.332 26 .638 37 .944 10.871 15 .805 28.854 4.998
MaSR Parkinso 10 19.551 20 .936 22 .321 1.3314 1. 9357 3.5339 0.6121
MaSR Diff (1-2) -4.877 5. 7021 16 .281 8.5077 11 .259 16.651 5.0353
T-Tests
Variable Method Variances DF t Value Pr > |t|
MaSR Pooled Equal 18 1.13 0.2723
MaSR Satterthwaite Unequal 9 .27 1.13 0.2859
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
MaSR Folded F 9 9 66.67 <.0001
Comparison in Cystatin A for Cstitis and KidSton 139
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Cstitis 10 5.736 8 .6302 11.524 2 .7829 4 .0458 7.3861 1.2794
CysA KidSton 10 2 .6438 3 .9607 5.2776 1 .2663 1 .8409 3.3608 0.5822
CysA Diff (1-2) 1 .7164 4 .6595 7.6226 2 .3749 3 .1431 4.648 1.4056 T-Tests
Variable Method Variances DF t Value Pr > |t|
CysA Pooled Equal 18 3.32 0. 0038 CysA Satterthwaite Unequal 12.6 3.32 0. O0S7
Equality of Variances
Variable Method Num DF Den DP F Value Pr > F
CysA Folded F 9 9 4.83 0.0281
Comparison in Cystatin A for Cstitis and Endoaden 140
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Cstitis 10 5.736 8.6302 11.524 2.7829 4.0458 7.3861 1.2794
CysA Endoaden 10 14.96 21.584 28.208 6.3694 9.26 16.905 2.9283
CysA Diff (1-2) -19.67 -12.95 -6.24 5.3992 7.1455 10.567 3.1956
T-Tests
Variable Method Variances DF t Value Pr > |t|
CysA Pooled Equal 18 -4.05 0.0007 CysA Satterthwaite Unequal 12.3 -4.05 0.0015
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 5.24 0.0215
Comparison in Cystatin A for Cstitis and Prostate
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean std Dev Std Dev Std Dev Std Err
CysA Cstitis 10 5.736 8.6302 11.524 2.7829 4.0458 7.3861 1.2794
CysA Prostate 10 0.6945 4.4912 8.2879 3.6506 5.3074 9.6892 1.6783
CysA Diff (1-2) -0.295 4.139 8.5727 3.5657 4.7189 6.9785 2.1104
T-Tests
Variable Method Variances t Value Pr > )t|
CysA Pooled Equal 18 1.96 0.0655 CysA Satterthwaite Unequal 16.8 1.96 0.0666
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 1.72 0.4311
Comparison in Cystatin A for Cstitis and Prostati 142
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Cstitis 10 5. 736 8.6302 11.524 2 .7829 4 .0458 7.3861 1.2794
CysA Prostati 10 23. 504 25.468 27.431 1 .8876 2 .7442 5.0099 0.8678
CysA Diff (1-2) -20 .09 -16.84 -13.59 2.612 3 .4568 5.1121 1.5459 T-Tests
Variable Method Variances DF t Value Pr > ItI
CysA Pooled Equal 18 -10 89 < 0001 CysA Satterthwaite Unequal 15.8 -10 89 < 0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 2 17 0 2630
Comparison m Cystatm A for Ostitis and Arthriti 143
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Arthriti 10 5 276 8 7172 12. 158 3 .3089 4.8105 8.7821 1 5212 CysA Ostitis 10 5 .736 8 6302 11. 524 2 7829 4.0458 7.3861 1 .2794 CysA Diff (1-2) -4. .089 0 087 4. 263 3 .3584 4.4446 6.5729 1 .9877
T-TestS
Variable Method Variances DF t Value Pr > |t|
CysA Pooled Equal 18 0. .04 0 9656 CysA Satterthwaite Unequal 17.5 0 .04 0 .9656
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 1.41 0 6143
Comparison in Cystatm A for Ostitis and Aortic 144
The TTEST Procedure Statistics
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Aortic 10 20 996 22 334 23 .672 1. 2866 1.8705 3 4147 0.5915 CysA Ostitis 10 5 736 8.6302 11 524 2.7829 4.0458 7.3861 1 2794 CysA Diff (1-2) 10.743 13 704 16 665 2.3815 3.1518 4.6609 1.4095
T-Tests
Variable Method Variances DF t Value Pr > |t|
CysA Pooled Equal 18 ( 3.72 < 0001 CysA Satterthwaite Unequal 12.7 3.72 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 4.68 0.0311
Comparison m Cystatm A for Cstitis and Parkmso 145
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Ostitis 10 5.736 8.6302 11 .524 2 .7829 4 .0458 7 .3861 1 .2794 CysA Parkinso 10 3 2408 3.4433 3. 6458 0 .1947 0 .2831 0 .5168 0 .0895 CysA Diff (1-2) 2.4924 5.18S9 7. 8814 2.167 2 .8678 4.241 1 .2825 T-Tests
Variable Method Variances DF t Value Pr > |t|
CysA Pooled Equal 18 4.04 0.0008 CysA Satterthwaite Unequal 9.09 4.04 0.0029
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 204.28 <.0001
Comparison in Cystatin A for KidSton and Endoaden 146
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Endoaden 10 14.96 21.584 28.208 6.3694 9.26 16.905 2.9283
CysA KidSton 10 2.6438 3.9S07 5.2776 1.2663 1.8409 3.3608 0.5822
CysA Diff (1-2) 11.351 17.623 23.896 5.0444 6.676 9.8726 2.9856
T-Tesfcs
Variable Method Variances t Value |t|
CysA Pooled Equal 18 5.90 <.0001 CysA Satterthwaite Unequal 9.71 5.90 0.0002
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 25.30 <.0001
Comparison in Cystatin A for KidSton and Prostate 147
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA KidSton 10 2.6438 3. 9607 5.2776 1.2663 1.8409 3.3608 0.5822
CysA Prostate 10 0.6945 4. 4912 8.2879 3.6506 5.3074 9.6892 1.6783
CysA Diff (1-2) -4.263 -0 .531 3.2016 3.0015 3.9722 5.8742 1.7764
T-Tests
Variable Method Variances t Value Pr > |t|
CysA Pooled Equal 18 -0.30 0.7686 CysA Satterthwaite Unequal 11.1 -0.30 0.7707
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 8.31 0.0042
Comparison in Cystatin A for KidSton and Prostati 148
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA. KidSton 10 2.6438 3.9607 5.2776 1 .2663 1 .8409 3 .3508 0.5822 CysA Prostati 10 23.504 25.468 27.431 1 .8876 2 .7442 5 .0099 0.8678 CysA Diff (1-2) -23.7 -21.51 -19.31 1 .7656 2 .3366 3 .4555 1.045 T-Tests
Variable Method Variances DF t Value Pr > |t|
CysA Pooled Equal 18 -20.58 <.0001 CysA Satterthwaite Unequal 15.7 -20.58 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 2.22 0.2500
Comparison in Cystatm A for KidSton and Arthriti
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Arthriti 10 5.276 8 .7172 12.158 3.3089 4.810Ξ 8.7821 1.5212
CysA KidSton 10 2 .6438 3 .9507 5.2776 1.2663 1.8409 3.3608 0.5822
CysA Diff (1-2) 1 .3345 4 .7565 8.1785 2.752 3.6421 5.3861 1.6288
T-Tests
Variable Method Variances t Value Pr > |t]
CysA Pooled Equal 18 2.92 0.0091 CysA Satterthwaite Unequal 11.6 2.92 0.0133
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 S .83 0.0086
Comparison in Cystatm A for KidSton and Aortic 150
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Aortic 10 20.996 22 .334 23 .672 1 .2866 1. 8705 3.4147 0 .5915 CysA KidSton 10 2 6438 3. 9607 5. 2776 1 .2663 1. 8409 3.3608 0 .5822 CysA Diff (1-2) 16.63 18 .373 20 .117 1 .4022 1. 8558 2.7443 0 .8299
T-Tests
Variable Method Variances DF t Value Pr » |t|
CysA Pooled Equal 18 22.14 < 0001 CysA Satterthwaite Unequal 18 22.14 < .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 1.03 0.9630
Comparison in Cystatm A for KidSton and Parkmso 151
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA KidSton 10 2 .6438 3 .9607 5 .2776 1 .2663 1 .8409 3.3608 0.5822
CysA Parkinso 10 3 .2408 3 .4433 3 .6458 0 .1947 0 .2831 0.5168 0.0895
CysA Diff (1-2) -0.72 0 .5174 1 .7548 0 .9952 1.317 1.9477 0.589 T-Tests
Variable Method Variances DF t Value Pr > |t|
CysA Pooled Equal 18 0.3913 CysA Satterthwaite Unequal 9.43 0.4015
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 42.30 <.0001
Comparison in Cystatin A for Endoaden and Prostate 152
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Endoaden 10 14.96 21 .584 28 .208 6 .3694 9.26 16.905 2 .9283 CysA Prostate 10 0.6945 4. 4912 8. 2879 3 .6506 5. 3074 9.6892 1 .6783 CysA Diff (1-2) 10.002 17 .093 24 .184 5 .7026 7 .547 11.161 3 .3751
T-Tests
Variable Method Variances DF t Value Pr > |t|
CysA Pooled Equal 18 5.06 < .0001 CysA Satterthwaite Unequal 14.3 5.06 0 .0002
Equality of Variances
Variable Method Num DP Den DF F Value Pr > F
CysA Folded F 9 9 3.04 0.1127
Comparison in Cystatin A for Endoaden and Prostati 153
The TTEST Procedure
Statistics
Lower CL Upper CL jower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Endoaden 10 14.96 21 .584 28.208 6.3694 9.26 16.905 2.9283
CysA Prostati 10 23.504 25 .468 27.431 1.8876 2.7442 5.0099 0.8678
CysA Diff (1-2) -10.3 -3 .884 2.5327 5.1603 6.8293 10.099 3.0542
T-Tests
Variable Method Variances DF t Value Pr > |t|
CysA Pooled Equal 18 -1.27 0.2197 CysA Satterthwaite Unequal 10.6 -1.27 0.2308
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 11.39 0.0013
Comparison in Cystatin A for Endoaden and Arthriti 154
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Arthriti 10 5.276 8.7172 12 .158 3 .3089 4 .8105 8. 7821 1.5212 CysA Endoaden 10 14.96 21.584 28 .208 6 .3694 9.26 16 .905 2.9283 CysA Diff (1-2) -19.8 -12.87 -5 .934 5 .5754 7 .3787 10 .912 3.2998 T-Tests
Variable Method Variances DF t Value Pr > |t|
CysA Pooled Equal 18 -3 90 0.0011 CysA Satterthwaxte Unequal 13.5 -3.90 0.0017
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 3.71 0 0643
Comparison in Cystatm A for Endoaden and Aortic 155
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev std Dev Std Dev Std Err
CysA Aortic 10 20.99β 22.334 23.672 1.2866 1.8705 3.4147 0.5915
CysA Endoaden 10 14.96 21.584 28.208 6.3694 9.26 16.905 2.9283
CysA Diff (1-2) -5.526 0.7503 7 0266 5.0475 6.6801 9.8786 2.9874
T-Tests
Variable Method Variances t Value Pr > |t|
CysA Pooled Equal 18 0.25 0.8045 CysA Satterthwaite Unequal 9.73 0.25 0.8069
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 24.51 <.0001
Comparison m Cystatm A for Endoaden and Parkmso 156
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Endoaden 10 14.96 21.584 28.208 6.3694 9.26 16.905 2.9283 CysA Parkmso 10 3.2408 3.4433 3.6458 0.1947 0.2831 0.5168 0.0895 CysA Diff (1-2) 11.986 18.141 24.295 4.9499 6.5509 9.6876 2.9296
T-Tests
Variable Method Variances t Value Pr > |t|
CysA Pooled Equal 18 6.19 <.0001 CysA Satterthwaite Unequal 9.02 6.19 0.0002
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 1070.13 <.0001
Comparison m Cystatm A for Prostate and Prostati
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Prostate 10 0.6945 4.4912 8.2879 3 .6506 5 .3074 9 .6892 1 .6783 CysA Prostati 10 23.504 25.468 27.431 1 .8876 2 .7442 5 .0099 0 .8678 CysA Diff (1-2) -24.95 -20.98 -17.01 3 .1924 4 .2249 6 .2478 1 .8894 T-Tests
Variable Method Variances DF t Value Pr > |t|
CysA Pooled Equal 18 -11 10 0001 CysA Satterthwaite Unequal 13.5 -11 10 < 0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 3 74 0 0625
Comparison m Cystatm A for Prostate and Arthriti 158
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev std Dev Std Dev Std Err
CysA Arthriti 10 5 276 8.7172 12.158 3.3089 4.8105 8 7821 1.5212
CysA Prostate 10 0 6945 4.4912 8 2879 3.6506 5.3074 9.6892 1 6783
CysA Diff (1-2) -0 533 4.226 8.9849 3.8272 5.065 7.4903 2.2652
T-Tests
Variable Method Variances DF t Value Pr > |t|
CysA Pooled Equal 18 1 87 0 0785 CysA Satterthwaite Unequal 17.8 1.87 0.0786
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 1 22 0 7744
Comparison in Cystatm A for Prostate and Aortic 159
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Aortic 10 20 .996 22.334 23.672 1 2866 1.8705 3.4147 0.5915 CysA Prostate 10 0 6945 4.4912 8 2879 3.6506 5 3074 9 6892 1.6783 CysA Diff (1-2) 14 104 17.843 21.582 3.0067 3.9791 5 8844 1.7795
T-Tests
Variable Method Variances DF t Value |t|
CysA Pooled Equal 18 10 03 <.0001 CysA Satterthwaite Unequal 11.2 10.03 ■=.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 8 05 0 0047
Comparison m Cystatm A for Prostate and Parkmso 160
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Parkmso 10 3. 2408 3. 4433 3.6458 0 .1947 0 .2831 0 .5168 0 .0895
CysA Prostate 10 0. 6945 4. 4912 8.2879 3 .6506 5 .3074 9 .6892 1 .6783
CysA Diff (1-2) -4 579 .048 2.4832 2 .8397 3 .7582 5 .5577 1 .6807 T-Tests
Variable Method Variances DF t Value Pr > It]
CysA Pooled Equal 18 -0.S2 0 .5408 CysA Satterthwaite Unequal 9.05 -0 62 0.5484
Equality of Variances
Variable Method Num DP Den DP F Value Pr > p
CysA Folded F 9 9 351.54 < 0001
Comparison in Cystatm A for Prostati and Arthriti 161
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Arthriti 10 5.276 8.7172 12.158 3.3089 4.8105 8.7821 1.5212
CysA Prostati 10 23.504 25.468 27.431 1.8876 2.7442 5.0099 0 8678
CysA Diff (1-2) -20.43 -16.75 -13.07 2.9591 3.9161 5.7913 1.7513
T-Tests
Variable Method Variances t Value Pr > |t|
CysA Pooled Equal 18 -9.56 <.0001 CysA Satterthwaite Unequal 14.3 -9.56 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 3.07 0.1099
Comparison m Cystatm A for Prostata, and Aortic 162
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Aortic 10 20. .996 22.334 23 .672 1 .2866 1.8705 3.4147 0. 5915 CysA Prostati 10 23. ,504 25.468 27 .431 1 .8876 2.7442 5.0099 0. 8678 CysA Diff (1-2) -5.34 -3.134 -0 .927 1 .7744 2 3483 3.4728 1. 0502
T-Tests
Variable Method Variances DF t Value Pr > |t|
CysA Pooled Equal 18 -2.98 0 .0080 CysA Satterthwaite Unequal 15.9 -2.98 0 .0088
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 2.15 0.2689
Comparison in Cystatm A for Prostati and Parkmso 163
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Parkmso 10 3.2408 3.4433 3.6458 0 .1947 0 .2831 0.5168 0.0895
CysA Prostati 10 23.504 25.468 27.431 1 .8876 2 .7442 5.0099 0.8678
CysA Diff (1-2) -23.86 -22.02 -20.19 1.474 1 .9508 2.8848 0.8724 T-Tests
Variable Method Variances DF t Value Pr > |t]
CysA Pooled Equal 18 -25.25 < 0001 CysA Satterthwaite Unequal 9.19 -25.25 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 93.98 <.0001
Comparison m Cystatm A for Arthriti and Aortic 1S4
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Aortic 10 20 .996 22 .334 23 .672 1 .2866 1 .8705 3.4147 0.5915 CysA Arthriti 10 S .276 8. 7172 12 .158 3 .3089 4 .8105 8.7821 1.5212 CysA Diff (1-2) 10 .188 13 .617 17 .046 2 .7577 3 .6496 5.3972 1.6322
T-Tests
Variable Method Variances DF t Value Pr |t|
CysA Pooled Equal 18 3.34 < 0001 CysA Satterthwaite Unequal 11.7 8.34 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
CysA Folded F 9 9 6.61 0.0096
Comparison in Cystatm A for Arthriti and Parkmso
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
CysA Arthriti 10 5.276 8 .7172 12.158 3.3089 4.8105 8.7821 1.5212
CysA Parkmso 10 3 .2408 3 .4433 3.6458 0.1947 0.2831 0.5168 0.0895
CysA Diff (1-2) 2 .0724 5 .2739 8.4754 2.5747 3.4074 5.039 1.5239
T-Tests
Variable Method Variances DF t Value Pr > |t|
CysA Pooled Equal 18 3.46 0.0028 CysA Satterthwaite Unequal 9.06 3.46 0.0071
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
CysA Folded F 9 9 288.80 <.0001
Comparison in Cystatm A for Aortic and Parkmso 166
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev std Dev Std Err
CysA Aortic 10 20 .996 22.334 23 .672 1 .2866 1 .8705 3.4147 0.5915
CysA Parkinso 10 3. 2408 3.4433 3. 6458 0 .1947 0 .2831 0.5168 0.0895
CysA Diff (1-2) 17 .634 18.891 20 .148 1 .0108 1 .3377 1.9782 0.5982 T-Tests
Variable Method Variances DP t Value Pr > t|
CysA Pooled Equal 18 31.58 < .0001 CysA Unequal 9 .41 31.58 < .0001
Equality of Variances
Variable Method Mum DF Den DF F Value Pr > F
CysA Folded F 9 9 43.66 <.0001
Comparison in Kallikrem 6 for Cstitis and KidSton 167
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 Cstitis 10 0. .9327 1 .6453 2.3599 0 .6862 0.997S 1.8212 0 .3155
KaI6 KidSton 10 0. .0927 0 .2052 0.3177 0 .1081 0.1572 0.287 0 .0497
Kale Diff (1-2) 0, .7701 1 .4411 2.1121 0 .5396 0.7141 1.056 0 .3194
T-Tests
Variable Method Variances DF t Value Pr > |t|
KaI6 Pooled Equal 18 4.51 0 .0003
Kal6 Satterthwaite Unequal 9 .45 4.51 0 .0013
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 40.26 <.0001
Comparison in Kallikrem 6 for Cstitis and Endoaden 168
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Kal6 Cstitis 10 0.9327 1.6463 2.3599 0.6862 0.9976 1.8212 0.3155
KaI6 Endoaden 10 1.0732 1.7948 2.5164 0.6938 1.0087 1.8415 0.319
Kal6 Diff (1-2) -1.091 -0.148 0.794 0.758 1.0032 1.4835 0.4486
T-Tests
Variable Method Variances DF t Value Pr > ]t|
Kal6 Pooled Equal 18 -0.33 0.7445 Kal6 Satterthwaite Unequal 18 -0.33 0.7445
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
KaIS Folded F 9 9 1.02 0.9742
Comparison in Kallikrem 6 for Cstitis and Prostate 169
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Kal6 Cstitis 10 0 .9327 1 .6463 2 .3599 0 .6862 0 .9976 1.8212 0.3155
Kal6 Prostate 10 0 .1475 0 .2519 0 .3563 0 .1004 0.146 0.2665 0.0462
Kal6 Diff (1-2) 0 .7246 1 .3944 2 .0642 0 .5387 0 .7129 1.0543 0.3188 T-Teεts
Variable Method Variances DF t Value Pr > |t|
Kal6 Pooled Equal 18 4 37 0.0004
KaI6 Satterthwaite Unequal 9.39 4 37 0.0016
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kalδ Folded F 9 9 46 70 < 0001
Comparison in Kallikrem 6 for Ostitis and Prostati 170
The TTEST Procedure Statistics
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 Ostitis 10 0 .9327 1 .6463 2 3599 0 6862 0.9976 1 8212 0. 3155
KaI6 Prostati 10 0 .4791 0 8199 1 1607 0 3277 0.4764 0 8697 0 1507
KaI6 Diff (1-2) 0 .0919 0 8264 1. 5609 0 5907 0.7817 1.156 0 3496
T-Tests
Variable Method Variances DF t Value Pr > |t|
Kal6 Pooled Equal 18 2 36 0 0295
KaI6 Satterthwaite Unequal 12 9 2 36 0 .0345
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 4.38 0.0383
Comparison in Kallikrem 6 for Cstitis and Arthπti 1
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 hriti 10 0 .4739 1. 2S51 2.0563 0 7607 1 106 2.0191 0 .3497 KaI6 ItIS 10 0 .9327 1. 6463 2.3599 0 .6862 0.9976 1.8212 0 .3155 KaI6 f (1-2) - 1 371 -0 .381 0.6083 0 .7958 1.0532 1.5575 0.471
T-Tests
Variable Method Variances DF t Value Pr > It|
KaI6 Pooled Equal 18 -0 81 0 4289
KaI6 Satterthwaite Unequal 17.8 -0 81 0 .4290
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F Kal6 Folded F 9 9 1.23 0.7636
Comparison in Kallikrem 6 for Cstitis and Aortic 1
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Kal6 Aortic 10 -0 .025 0 .0467 0. 1189 0 .0694 0 .1009 0 .1841 0 .0319
Kal6 Cstitis 10 0. 9327 1 .6463 2. 3599 0 .6862 0 .9976 1 .8212 0 .3155
Kal6 Diff (1-2) -2 .266 -1.6 -0 .933 0 .5357 0.709 1 .0485 0 .3171 T-Tests
Variable Method Variances DF t Value Pr > |t|
KaI6 Pooled Equal 18 -5 04 < 0001
Kal6 Satterthwaite U Unneeqquuaall 9 18 -5 04 0 0007
Equality of Variances
Variable Method Num DP Den DP F Value Pr > F
Kal6 Folded F 9 9 97 82 < 0001
Comparison m Kallikrem 6 for Ostitis and Parkmso
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Kal6 Cstitis 10 0 9327 1 6463 2 3599 0 6862 0 9976 1 8212 0 3155
KaI6 Parkmso 10 2 3845 2 602S 2 8207 0 2097 0 3048 0 5565 0 0964
KaI6 Diff (1-2) -1 649 0 956 -0 263 0 5573 0 7376 1 0908 0 3299
T Tests
Variable Method Variances t Value Pr > |t|
KaI6 Pooled Equal 18 -2 90 0 0096
Kal6 Satterthwaite Unequal 10 7 2 90 0 0149
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 10 71 0 0016
Comparison in Kallikrein 6 for Kidston and Endoaden 174
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 Endoaden 10 1 0732 1 7948 2 5164 0 6938 1 0087 1 8415 0 319
KaI6 KidSton 10 0 0927 0 2052 0 3177 0 1081 0 1572 0 287 0 0497
KaI6 Diff (1-2) 0 9114 1 5896 2 2678 0 5455 0 7219 1 0675 0 3228
T-Tests
Variable Method Variances t Value Pr > |t|
KaI6 Pooled Equal 18 4 92 0 0001 Kal6 Satterthwaite Unequal 9 44 4 92 0 0007
Equality of Variances
Variable Method Num DF Den DF F Value Pr > P
Kal6 Folded F 9 9 41 16 < 0001
Comparison m Kallikrem 6 for KidSton and Prostate 175
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 KidSton 10 0 0927 0 2052 0 3177 0 1081 0 1572 0 287 0 0497
KaI6 Prostate 10 0 1475 0 2519 0 3563 0 1004 0 146 0 2665 0 0462
KaI6 Diff (1-2) -0 189 -0 047 0 0958 0 1146 0 1S17 0 2243 0 0678 T-Tests
Variable Method Variances DF t Value Pr > ItI
Kal6 pooled Equal 18 -0.69 0.5000
KaIS Satterthwaite Unequal 17.9 -0.69 0.5001
Equality of Variances
Variable Method Num DP Den DP P Value Pr > F
Kal6 Folded P 9 9 1 16 0.8285
Comparison m Kallikrem 6 for KidSton and Prostati 17S
The TTEST Procedure Statistics
Lower CL upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 KidSton 10 0.0927 0. 2052 0.3177 0 .1081 0.1572 0.287 0. 0497
KaI6 Prostati 10 0.4791 0. 8199 1 1607 0 .3277 0.4764 0.8697 0. 1507
KaI6 Diff (1-2) -0.948 -0 .615 -0.281 0 .2681 0.3547 0.5246 0. 15S6
T-Tests
Variable Method Variances DF t Value Pr > |t|
KaI6 Pooled Equal 18 -3.87 0.0011
Kal6 Satterthwaite unequal 10.9 -3.87 0.0026
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 9.18 0.0029
Comparison in Kallikrem 6 for KidSton and Arthriti
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Kal6 Arthriti 10 0 .4739 1 .2651 2 .0563 0 .7607 1.106 2.0191 0.3497
Kal6 KidSton 10 0 .0927 0 .2052 0 .3177 0 .1081 0 .1572 0.287 0.0497
Kal6 Diff (1-2) 0 .3177 1 .0599 1 .8021 0 .5969 0 .7899 1.1681 0.3533
T-Tests
Variable Method Variances DF t Value Pr > |t|
Kal6 Pooled Equal 18 3.00 0.0077 KaI6 Satterthwaite Unequal 9.36 3 00 0.0143
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 49.48 <.0001
Comparison in Kallikrem 6 for KidSton and Aortic 178
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 Aortic 10 -0.025 0.0467 0.1189 0 .0694 0 .1009 0.1841 0 .0319
KaI6 KidSton 10 0.0927 0.2052 0.3177 0 .1081 0 .1572 0.287 0 .0497
KaI6 Diff (1-2) -0.283 -0.159 -0.034 0 .0998 0 .1321 0.1953 0 .0591 T-Tests
Variable Method Variances DF t Value Pr > 1 t1
KaI6 Pooled Equal 18 -2 68 0.0152 Kal6 Satterthwaite Unequal IS.3 -2.68 0.0168
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded P 9 9 2.43 0.2021
Comparison in Kallikrem 6 for KidSton and Parkinso 179
The TTEST Procedure Statistics
Lower CL Upper CB Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev std Dev Std Err
KaI6 Ston 10 0.0927 0.2052 0.3177 0 1081 0.1572 0.287 0 .0497 Kal6 kmso 10 2.3845 2.6026 2.8207 0 .2097 0.3048 0.5565 0 .0964 KaIS f (1-2) -2.625 -2.397 -2.17 0 .1833 0 2425 0.3587 0 .1085
T-Tests
Variable Method Variances DF t Value Pr > |t|
KaI6 Pooled Equal 18 -22 .10 < .0001
Kal6 Satterthwaite Unequal 13.5 -22 .10 < .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 3 76 0.0616
Comparison in Kallikrem 6 for Endoaden and Prostate 180
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Kal6 Endoaden 10 1 .0732 1 .7948 2 .5164 0 .6938 1 .0087 1.8415 0.319
Kal6 Prostate 10 0 .1475 0 .2519 0 .3563 0 .1004 0.146 0.2665 0.0462
Kalδ Diff (1-2) 0 .8658 1 .5429 2.22 0 .5446 0 .7207 1.0658 0.3223
T-Tests
Variable Method Variances t Value Pr |t|
KaI6 Pooled Equal 18 4.79 0.0001 KaI6 Satterthwaite Unequal 9.38 4.79 0.0009
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 47.75 <.0001
Comparison in Kallikrem 6 for Endoaden and Prostati 181
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 Endoaden 10 1.0732 1.7948 2.5164 0.6938 1 .0087 1 .8415 0.319
Kal6 Prostati 10 0.4791 0 .8199 1.1607 0.3277 0 .4764 0 .8697 0 .1507
Kal6 Diff (1-2) 0.2338 0.9749 1.716 0.596 0 .7888 1 .1665 0 .3528 T-Tests
Varxable Method Variances DP t Value Pr > ]t|
Kal6 Pooled Equal 18 2 76 0 0128 Kalδ Satterthwaite Unequal 12 8 2 76 0 0163
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 4 48 0 0357
Comparison m Kallikrem 6 for Endoaden and Arthriti 182
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Kal6 Arthriti 10 0 4739 1 2651 2 0563 0 7607 1 106 2 0191 0 3497
KaI6 Endoaden 10 1 0732 1 7948 2 5164 0 6938 1 0087 1 8415 0 319
KaI6 Diff (1-2) -1 524 -0 53 0 4648 0 7998 1 0585 1 5653 0 4734
T-Tests
Variable Method Variances DF t Value Pr |t|
KaI6 Pooled Equal 18 -1 12 0 2778 Kal6 Satterthwaite Unequal 17 8 -1 12 0 2780
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 1 20 0 7883
Comparison in Kallikrem 6 for Endoaden and Aortic 183
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 Aortic 10 -0 025 0 0467 0 1189 0 0694 0 1009 0 1841 0 0319
KaI6 Endoaden 10 1 0732 1 7948 2 5164 0 6938 1 0087 1 8415 0 319
Kal6 Diff (1-2) -2 422 -1 748 -1 075 0 5416 0 7168 1 06 0 3206
T-Tests
Variable Method Variances t Value Pr > |t|
KaI6 Pooled Equal 18 -5 45 < 0001 KaI6 Satterthwaite Unequal 9 18 -5 45 0 0004
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 100 01 < 0001
Comparison in Kallikrem 6 for Endoaden and Parkinso 184
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Kal6 Endoaden 10 1 0732 1 7948 2 5164 0 6938 1 0087 1 8415 0 319
Kal6 Parkinso 10 2 3845 2 6026 2 8207 0 2097 0 3048 0 5565 0 0964
KaI6 Diff (1-2) -1 508 -0 808 -0 108 0 563 0 7451 1 1019 0 3332 T-Tests
Variable Method Variances DF t Value Pr > |t|
Kal6 Pooled Equal 18 -2.42 0.0261 KaIS Satterthwaite Unequal 10.6 -2.42 0.0345
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 10.95 0.0015
Comparison in Kallikrein 6 for Prostate and Prostati 185
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 Prostate 10 0.1475 0. 2519 0.3563 0.1004 0.146 0.2665 0.0462
Kal6 Prostati 10 0.4791 0. 8199 1.1607 0.3277 0.4764 0.8697 0.1507
KaI6 Diff (1-2) -0.899 -0 .568 -0.237 0.2662 0.3523 0.521 0.1576
T-Tests
Variable Method Variances t Value Pr > |t|
KaI6 Pooled Equal 18 -3.60 0.0020 Kal6 Satterthwaite- Unequal 10.7 -3.60 0.0043
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 10.65 0.0016
Comparison in Kallikrein 6 for Prostate and Arthriti 186
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 Arthriti 10 0.4739 1 .2651 2.0563 0.7607 1.106 2.0191 0.3497
KaI6 Prostate 10 0.1475 0 .2519 0.3563 0.1004 0.146 0.2665 0.0462
Kal6 Diff (1-2) 0.272 1 .0132 1.7544 0.596 0.7888 1.1665 0.3528
T-Tests
Variable Method Variances DF t Value Pr > |t|
KaI6 Pooled Equal 18 2.87 0.0101 Kal6 Satterthwaite Unequal 9.31 2.87 0.0178
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 57.40 <.0001
Comparison in Kallikrein 6 for Prostate and Aortic 187
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 Aortic 10 -0 .025 0. 0467 0.1189 0 .0694 0 .1009 0.1841 0.0319
KaI6 Prostate 10 0. 1475 0. 2519 0.3563 0 .1004 0.146 0.2665 0.0462
Kal6 Diff (1-2) -0 .323 -0 .205 -0.087 0 .0948 0 .1255 0.1855 0.0561 T-Tests
Variable Method Variances DF t Value Pr > |t|
KaIS Pooled Equal 18 -3.66 0 .0018 KaIS Satterthwaite Unequal 16 -3.66 0 0021
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
KaIS Folded F 9 9 2 09 0.2859
Comparison in Kallikrem S for Prostate and Parkmso 188
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaIS kmso 10 2 384S 2 .6026 2.8207 0 .2097 0. 3048 0 5565 0 .0964 KaI6 state 10 0 1475 0 .2519 0.3563 0 .1004 0 .146 0.2665 0 .0462 Kal6 f (1-2) 2 1262 2 .3507 2.5752 0 .1806 0 239 0.3534 0 1069
T-TeStS
Variable Method Variances DF t Value Pr > |t|
KaIS Pooled Equal 18 21 99 < .0001
KaIS Satterthwaite Unequal 12 9 21.99 < .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 4.36 0.0390
Comparison m Kallikrem 6 for Prostati and Arthriti
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaIS Arthriti 10 0. 4739 1 .2651 2.0563 0 7607 1.106 2.0191 0.3497
KaI6 Prostati 10 0 4791 0 .8199 1 1607 0 3277 0.47S4 0.8697 0.1507
KaI6 Diff (1-2) -0 .355 0 .4452 1 2453 0.6434 0.8515 1.2592 0.3808
T-Tests
Variable Method Variances t Value Pr > |t|
KaIS Pooled Equal 18 1.17 0.2576 KaI6 Satterthwaite Unequal 12.2 1.17 0 2S47
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
KaIS Folded F 9 9 5.39 0.0195
Comparison in Kallikrem 6 for Prostati and Aortic 190
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 Aortic 10 -0.025 0. 0467 0 .1189 0 .0694 0 .1009 0.1841 0.0319
KaIS Prostati 10 0.4791 0. 8199 1 .1607 0 .3277 0 .4764 0.8697 0.1507
KaIS Diff (1-2) -1.097 -0 .773 -0.45 0 .2602 0 .3443 0.5092 0.154 T-Tests
Variable Method Variances DF t Value Pr > jt|
Kal6 Pooled Equal 18 -5.02 <.oooi
KaIS Satterthwaite Unequal 9.Bl -5.02 0.0006
Equality of Variances
Variable Method Num DF Den DF P Value Pr > F
Kal6 Folded F 9 9 22.31 <.0001
Comparison in Kallikrein 6 for Prostati and Parkinso 191
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 Parkinso 10 2 .3845 2 .602S 2.8207 0.2097 0.3048 0.5565 0.09S4
KaIS Prostati 10 0 .4791 0 .8199 1.1607 0.3277 0.4764 0.8697 0.1507
KaI6 Diff (1-2) 1 .4069 1 .7827 2.1585 0.3022 0.3999 0.5914 0.1789
T-Tests
Variable Method Variances DF t Value Pr > |t|
KaI6 Pooled Equal 18 9.97 <.0001 Kal6 Satterthwaite Unequal 15.3 9.97 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kalδ Folded F 9 9 2.44 0.1995
Comparison in Kallikrein S for Arthriti and Aortic 192
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 Aortic 10 -0 .025 0.04S7 0.1189 0.0694 0.1009 0.1841 0.0319
KaIS Arthriti 10 0. 4739 1.2651 2.0563 0.7607 1.106 2.0191 0.3497
KaI6 Diff (1-2) —1 .956 -1.218 -0.481 0.5934 0.7853 1.1613 0.3512
T-Tests
Variable Method Variances t Value Pr > |t|
Kal6 Pooled Equal 18 -3.47 0.0027 KaIS Satterthwaite Unequal 9.15 -3.47 0.0069
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 120.24 <.0001
Comparison in Kallikrein 6 for Arthriti and Parkinso 193
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 Arthriti 10 0.4739 1. 2651 2.05S3 0.7607 1.106 2.0191 0.3497
KaI6 Parkinso 10 2.3845 2. 6026 2.8207 0.2097 0.3048 0.5565 0.0964
KaI6 Diff (1-2) -2.1 -1 .338 -0.575 0.613 0.8112 1.1996 0.3628 T-Tests
Variable Method Variances DF t Value Pr > | t |
Kal6 Pooled Equal 18 -3 .69 0 .0017 Kal6 Satterthwaite Unequal 10.4 -3 .69 0 .0040
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F Kal6 Folded F - 9 9 13.16 0.0007
Comparison in Kallikrein 6 for Aortic and Parkinso 1
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
KaI6 Aortic 10 -0 .025 0. 0467 0.1189 0 .0694 0.1009 0 .1841 0 .0319
Kal6 Parkinso 10 2.384S 2. 6026 2.8207 0 .2097 0.3048 0 .5565 0 .0964
KaI6 Diff (1-2) -2 .769 -2 .556 -2.343 0 .1716 0.227 0 .3358 0 .1015
T-Tests
Variable Method Variances DF t Value Pr > |t|
Kal6 Pooled Equal 18 -25 .17 < .0001
KaI6 Satterthwaite Unequal 10.9 -25 .17 < .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Kal6 Folded F 9 9 9.13 0.0029
Comparison in Alpha synuclein for Ostitis and KidSton 195
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS Ostitis 10 18 .184 26.039 33.894 7.5528 10.981 20.046 3.4724
AIpS KidSton 10 13 .111 15.752 18.392 2.5392 3.6916 6.7395 1.1674
Alps Diff (1-2) 2. 5908 10.287 17.984 6.1896 8.1915 12.114 3.6633
T-Tests
Variable Method Variances DF t Value Pr > |t|
AIpS Pooled Equal 18 2.81 0.0116 AIpS Satterthwaite Unequal 11 2.81 0.0170
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AIpS Folded F 9 9 8.85 0.0033
Comparison in Alpha synuclein for Ostitis and Endoaden 196
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Alps Ostitis 10 18.184 26.039 33 .894 7. 5528 10 .981 20 .046 3 .4724 Alps Endoaden 10 27.43 36.715 45 .999 8. 9272 12 .979 23 .694 4 .1042 Alps Diff (1-2) -21.97 -10.68 0. 6186 9. 0834 12 .021 17 .777 5.376 T-Tests
Variable Method Variances DF t Value Pr > ]t|
AIpS Pooled Equal 18 -1.99 0 0625 AIpS Satterthwaite Unequal 17 5 -1.99 0.0629
Equality of Variances
Variable Method Num DF Den DP F Value Pr > F AIpS Folded F 9 9 1.40 0.6265
Comparison m Alpha synuclem for Cstitis and Prostate 197
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL Variable Disease N Mean Mean Mean Std Dev Std Dev std Dev Std Err
AIpS CstitlS 10 18.184 26.039 33.894 7.5528 10.981 20.046 3.4724 AIpS Prostate 10 2.9203 5.7392 8.5581 2.7104 3.9405 7.1939 1.2461 AIpS Dlff (1-2) 12.549 20.3 28.05 6.2333 8.2493 12.199 3.6892
T-Tests Variable Method Variances DF t Value Pr > 111
AIpS Pooled Equal 18 5.50 <.0001
AIpS Satterthwaite Unequal 11.3 5.50 0.0002
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F AIpS Folded F 9 9 7.76 0.0054
Comparison xn Alpha synuclem for Cstitis and Prostati 198
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS Cstitis 10 18.184 26.039 33.894 7.5528 10.981 20.046 3.4724 AIpS Prostati 10 29.25 35.097 40.945 5.6223 8.1739 14.922 2.5848 AIpS Dlff (1-2) -18.15 -9.059 0.0359 7.3139 9.6795 14.314 4.3288
T-Tests Variable Method Variances DF t Value Pr > |t|
Alps Pooled Equal 18 -2.09 0.0508
Alps Satterthwaite Unequal 16.6 -2.09 0.0520
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F Alps Folded F 9 9 1.80 0.3923
Comparison in Alpha synuclem for Cstitis and Arthπti 199
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL Variable Disease N N M Meeaann M Meeaann Mean Std Dev Std Dev Std Dev Std Err
AIpS Arthriti 10 32.819 37 .238 41. 658 4 .2493 6. 1777 11 .278 1 .9536 AIpS Cstitis 10 18.184 26 .039 33. 894 7 .5528 10 .981 20 .046 3 .4724 Alps Dlff (1-2) 2.8291 11.2 19 .57 6 .7317 8. 9089 13 .175 3 .9842 T-Tests
Variable Method Variances DP t Value Pr ^ |t|
AIpS Pooled Equal 18 2.81 0.0116 AIpS Satterthwaite Unequal 14.2 2.81 0.0137
Equality of Variances
Variable Method Nura DF Den DP F Value Pr > F AIpS Folded F 9 9 3.16 0.1017
Comparison m Alpha synuclem for Ostitis and Aortic 2
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL Variable Disease N N M Meeaann M Meeaann Mean Std Dev Std Dev Std Dev Std Err
AIpS Aortic 1 100 1 133..555544 1 144.. 227744 14.994 0.6923 1.0064 1.8374 0.3183
AIpS Cstitis 1 100 1 188..118844 2 266.. 003399 33.894 7.SS28 10.981 20.046 3.4724
AIpS Diff (1-2) - -1199..0099 - -1111 ..7777 -4.439 5.8915 7.797 11.53 3.4869
T-Tests
Variable Method Variances DF t Value Pr > | t |
Alps Pooled Equal 18 -3.37 0.0034 AIpS Satterthwaite Unequal 9.15 -3.37 0.0080
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Alps Folded F 9 9 119.03 <.0001
Comparison in Alpha synuclem for Cstitis and Parkinso 201
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N M Meeaann M Meeaann Mean Std Dev Std Dev Std Dev Std Err
AIpS Cstitis 1100 1188..118844 2266 ..003399 33.894 7.5528 10.981 20.046 3.4724 AIpS Parkmso 1100 2233..663399 2244 ..557722 25.505 0.8969 1.3039 2.3805 0.4123 AIpS Dlff (1-2) --55..8888 11.. 44666699 8.8133 5.9081 7.819 11.563 3.4968
T-Tests Variable Method Variances DF t Value Pr > | t|
AIpS Pooled Equal 18 0.42 0.6798
AIpS Satterthwaite Unequal 9.25 0.42 0.6844
Equality o£ Variances
Variable Method Nura DF Den DF F Value Pr > F Alps Folded F 9 9 70.92 <.0001
Comparison in Alpha synuclem for KidSton and Endoaden 202
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS Endoaden 10 27.43 36.715 45 .999 8 .9272 12 .979 23.694 4 .1042 AIpS KidSton 10 13.111 15.752 18 .392 2 .5392 3. 6916 6.7395 1 .1674 AIpS Dlff (1-2) 11.999 20.963 29 .928 7 .2095 9. 5413 14.11 4.267 T-Tests
Variable Method Variances DF t Value Pr > It|
AIpS Pooled Equal 18 4 91 0 0001 AIpS Satterthwaite Unequal 10.4 4.91 0 0005
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AIpS Folded F 9 9 12 36 0 0009
Comparison m Alpha synuclem for KidSton and Prostate 203
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS KidSton 10 13.111 15.752 18.392 2.5392 3.S916 6.7395 1.1S74
AIpS Prostate 10 2.9203 5.7392 8 5581 2.7104 3.9405 7 1939 1.2461
AIpS Diff (1-2) 6.4251 10.012 13.6 2 885 3.8181 5.6463 1 7075
T-Tests
Variable Method Variances t Value Pr > |t|
AIpS Pooled Equal 18 5.86 <-0001 AIpS Satterthwaite Unequal 17 9 5.86 < 0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AIpS Folded F 9 9 1 14 0.8490
Comparison in Alpha synuclem for KidSton and Prostati 204
The TTEST Procedure Statistics
Lower CB Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS KidSton 10 13.111 15.752 18.392 2.5392 3.6916 6 7395 1 1674
AIpS Prostati 10 29.25 35.097 40 945 5.6223 8.1739 14.922 2.5848
AIpS Diff (1-2) -25.3 -19.35 -13 39 4.792 6.3419 9.3786 2.8362
T-Tests
Variable Method Variances t Value Pr > |t|
AIpS Pooled Equal 18 -6.82 <.0001 AIpS Satterthwaite Unequal 12.5 -6.82 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AIpS Folded F 9 9 4.90 0 0267
Comparison m Alpha synuclein for KidSton and Arthriti 205
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS Arthriti 10 32.819 37.238 41.658 4 .2493 6 .1777 11 .278 1 .9536 AIpS KidSton 10 13.111 15.752 18.392 2 .5392 3 .6916 6. 7395 1 .1674 AIpS Diff (1-2) 16.706 21.487 26.268 3 .8452 5 .0888 7. 5255 2 .2758 T-Tests
Variable Method Variances DF t Value Pr > |t|
AIpS Pooled Equal 18 9 44 <-0001 AIpS Satterthwaite Unequal 14 7 9.44 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr =■ F AIpS Folded F 9 9 2.80 0.1410
Comparison in Alpha synuclem for KidSton and Aortic 2
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS tic 10 13, .554 14 .274 14.994 0 .6923 1.0064 1.8374 0 .31B3 AIpS Ston 10 13. .111 15 .752 18.392 2 .5392 3.6916 6.7395 1 .1674 AIpS f (1-2) -4.02 -1 .478 1.0642 2 .0444 2.7056 4.0012 1.21
T-Tests
Variable Method Variances DF t Value Pr > |t|
AIpS Pooled Equal 18 -1.22 0 .2377
AIpS Satterthwaite Unequal 10.3 -1.22 0 .2491
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F AIpS Folded F 9 9 13.45 0.0007
Comparison m Alpha synuclem for KidSton and Parkmso 207
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS KidSton 10 13.111 15.752 18.392 2.5392 3.6916 6.7395 1.1674 AIpS Parkmso 10 23.639 24.572 25.505 0.8969 1.3039 2.3805 0.4123 AIpS Dlff (1-2) -11.42 -8.82 -6.219 2.0919 2.7684 4.094 1.2381
T-Tests Variable Method Variances DF t Value Pr > |t|
Alps Pooled Equal 18 -7.12 <.0001
AIpS Satterthwaite Unequal 11.2 -7.12 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F AIpS Folded F 9 9 8.02 0.0048
Comparison m Alpha synuclem for Endoaden and Prostate 208
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL Variable Disease N N M Meeaann M Meeaann Mean Std Dev Std Dev Std Dev Std Err
AIpS Endoaden 10 27.43 36.715 45.999 8 .9272 12 .979 23 .694 4 .1042 Alps Prostate 10 2.9203 5.7392 8.5581 2 .7104 3. 9405 7. 1939 1 .2461 AIpS Diff (1-2) 21.964 30.976 39.987 7.247 9 .591 14 .183 4 .2892 T-Tests
Variable Method Variances DF t Value Pr >
AIpS Pooled Equal 18 7.22 <.0001 AIpS Satterthwaite Unequal 10.6 7.22 <.0001
Equality of Variances
Variable Method Num DP Den DF F Value Pr > F
AIpS Folded F 9 9 10.85 0.0015
Comparison in Alpha synuclein for Endoaden and Prostati 209
The TTEST Procedure
Statistics
Lower CL Upper CL jower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS Endoaden 10 27.43 36. .715 45.999 8.9272 12.979 23.694 ■, 4.1042
AIpS Prostati 10 29.25 35. .097 40.945 5.6223 8.1739 14.922 ' 2.5848
AIpS Diff (1-2) -8.573 l-r6174 11.808 8.1951 10.846 16.039 4.8503
T-Tests
Variable Method Variances DF t Value Pr |t|
AIpS Pooled Equal 18 0.33 0.7426 rAlpS Satterthwaite Unequal 15.2 0.33 0.7434
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AIpS Folded F 9 9 2.52 0.1845
Comparison in Alpha synuclein for Endoaden and Arthriti
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS hriti 10 32. .819 37 .238 41. S58 4. 2493 6. 1777 11.278 1 .9536 AIpS oaden 10 27.43 36 .715 45. 999 8. 9272 12 .979 23.694 4 .1042 AIpS f (1-2) -9. .026 0. 5236 10. 073 7.58 10 .164 15.031 4 .5454
T-Tests
Variable Method Variances DF t Value Pr > |t|
AIpS Pooled Equal 18 0.12 0 .9096
AIpS Satterthwaite Unequal 12.9 0.12 0 .9101
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F AIpS Folded F 9 9 4.41 0.0375
Comparison in Alpha synuclein for Endoaden and Aortic 211
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS Aortic 10 13.554 14.274 14. 994 0 .6923 1. 0064 1. 8374 0 .3183 AIpS Endoaden 10 27.43 36.715 45. 999 8 .9272 12 .979 23 .694 4 .1042 AIpS Diff (1-2) -31.09 -22.44 -13 .79 6 .9553 9. 2048 13 .612 4 .1165 T-Tests
Variable Method Variances DF t Value Pr > |t|
Alps Pooled Equal 18 -5.45 <.0001 Alps Satterthwaite Unequal 9.11 -S.45 0.0004
Equality of Variances
Variable Method Num DF Den DP F Value Pr > F
AIpS Folded F 9 9 ISS.30 <.0001
Comparison in Alpha synuclein for Endoaden and Parkinso 212
The TTEST Procedure Statistics
Lower CL upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Alps Endoaden 10 27.43 36.715 45.999 8. .9272 12 .979 23.694 4.1042 Alps Parkinso 10 23.S39 24.572 25.505 0..8969 1.3039 2.3805 0.4123 AIpS Diff (1-2) 3.4769 12.143 20.809 ε..9694 9.2235 13.64 4.1249
T-Tests
Variable Method Variances DF t Value Pr > |t|
AIpS Pooled Equal 18 2.94 0.0087 Alps Satterthwaite Unequal 9.18 2.94 0.0160
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F AIpS Folded F 9 9 99.07 <-0001
Comparison in Alpha synuclein for Prostate and Prostati 213
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N N M Meeaann M Meeaann Mean Std Dev Std Dev Std Dev Std Err
AIpS Prostate 1100 22..99220033 55..77339922 8.5581 2.7104 3.9405 7.1939 1.2461 AIpS Prostati 1100 2299..2255 3355..009977 40.945 5.6223 8.1739 14.922 2.5848 AIpS Diff (1-2) --3355..3399 --2299..3366 -23.33 4.8483 S.4164 9.4887 2.8695
T-Tests Variable Method Variances DF t Value Pr > | t |
AIpS Pooled Equal 18 -10.23 <.0001 AIpS Satterthwaite Unequal 13 -10.23 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F AIpS Folded F 9 9 4.30 0.0407
Comparison in Alpha synuclein for Prostate and Arthriti 214
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS Arthriti 10 32.819 37.238 41.658 4 .2493 6 .1777 11 .278 1 .9536 AIpS Prostate 10 2.9203 5.7392 8.5581 2 .7104 3 .9405 7. 1939 1 .24Sl AIpS Diff (1-2) 26.631 31.499 36.367 3 .9151 S .1813 7. 6623 2 .3172 T-Tests
Variable Method Variances DF t Value Pr > |t|
AIpS Pooled Equal 18 13.59 <.0001 AIpS Satterthwaite Unequal 15.3 13.59 <.0001
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
AIpS Folded F 9 9 2.46 0 1965
Comparison in Alpha synuclem for Prostate and Aortic 215
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Alps Aortic 10 13.554 14 .274 14.994 0.6923 1.0064 1.8374 0.3183
Alps Prostate 10 2.9203 5. 7392 8.5581 2.7104 3.9405 7.1939 1.2461
Alps Diff (1-2) 5.8325 8. 5345 11 237 2.173 2.8758 4.2528 1.2861
T-Tests
Variable Method Variances t Value Pr > |t|
AIpS Pooled Equal 18 6.64 <.0001 AIpS Satterthwaite Unequal 10.2 6.64 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AIpS Folded F 9 9 15.33 0.0004
Comparison in Alpha synuclem for Prostate and Parkmso
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Alps Parkinso 10 23.639 24 .572 25.505 0.8969 1.3039 2.3805 0.4123
AIpS Prostate 10 2.9203 5 7392 8.5581 2.7104 3.9405 7.1939 1.2461
AIpS Diff (1-2) 16.075 18 833 21.59 2.2177 2.935 4.3403 1.3126
T-Tests
Variable Method Variances t Value Pr > | t |
AIpS Pooled Equal 18 14.35 <.0001 AIpS Satterthwaite Unequal 10.9 14.35 ■=.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AIpS Folded F 9 9 9.13 0.0029
Comparison in Alpha synuclein for Prostati and Arthnti 217
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Alps Arthπti 10 32.819 37.238 41.658 4.2493 6. mi 11.278 1.9536
Alps Prostati 10 29.25 35.097 40.945 5.6223 8.1739 14.922 2.5848
AIpS Diff (1-2) -4.666 2.141 8.948 5.4743 7.2449 10.714 3.24 T-Tests
Variable Method Variances DP t Value Pr > ItI
AIpS Pooled Equal 18 0.66 0 5171 AIpS Satterthwaite Unequal 16.8 0.S6 0 5177
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AIpS Folded F 9 9 1.75 0 4168
Comparison in Alpha synuclem for Prostati and Aortic 218
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS Aortic 10 13.554 14.274 14.994 0. .6923 1.0064 1.8374 0. 3183 AIpS Prostati 10 29.25 35.097 40.945 5 6223 8.1739 14.922 2.5848 AIpS Dlff (1-2) -26.3 -20.82 -15.35 4..4003 5.8234 8.6118 2.6043
T-Tests
Variable Method Variances DF t Value Pr > |t|
AIpS Pooled Equal 18 -i 3.00 <.0001 AIpS Satterthwaite Unequal 9.27 -i3.00 <.0O01
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AIpS Folded F 9 9 65.96 <.0001
Comparison in Alpha synuclem for Prostati and Parkmso 219
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS Parkmso 10 23.639 24.572 25.505 0.8969 1.3039 2.3805 0.4123
AIpS Prostati 10 29.25 35.097 40.945 5.6223 8.1739 14.922 2.5848
AIpS Dlff (1-2) -16.02 -10.53 -5.02S 4.4225 5.8529 8.6554 2.6175
T-Tests
Variable Method Variances t Value Pr > |t|
AIpS Pooled Equal 18 -4.02 0.0008 AIpS Satterthwaite Unequal 9.46 -4.02 0 0027
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AIpS Folded F 9 9 39.30 <.0001
Comparison in Alpha synuclem for Arthriti and Aortic 220
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Alps Aortic 10 13.554 14.274 14. 994 0 .6923 1 .0064 1. 8374 0 .3183 AIpS Arthriti 10 32.819 37.238 41. 658 4 .2493 6 .1777 11 .278 1 .9536 AIpS Diff (1-2) -27.12 -22.96 -18 .81 3 .3443 4 .4259 6. 5451 1 .9793 T-Tests
Variable Method Variances DF t Value Pr > |t|
AIpS Pooled Equal 18 -11.60 <.0001 AIpS Satterthwaite unequal 9.48 -11.60 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F AIpS Folded F 9 9 37.68 <.0001
Comparison in Alpha synuclein for Arthriti and Parkinso 221
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS Arthriti 10 32.819 37.238 41.6S8 4.2493 6.1111 11.278 1.9536 AIpS Parkinso 10 23.639 24.572 25.505 0.8969 1.3039 2.3805 0.4123 AIpS DiEf (1-2) 8.4718 12.667 16.861 3.3735 4.4646 6.6023 1.99S6
T-Tests Variable Method Variances DF t Value Pr > |t|
AIpS Pooled Equal 18 6.34 <.0001 AIpS Satterthwaite Unequal 9.8 6.34 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F AIpS Folded F 9 9 22.45 <.0001
Comparison in Alpha synuclein for Aortic and Parkinso 222
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AIpS Aortic 10 13.554 14.274 14.994 0.6923 1.0064 1.8374 0.3183
AIpS Parkinso 10 23.639 24.572 25.505 0.8969 1.3039 2.3805 0.4123 AIpS Diff (1-2) -11.39 -10.3 -9.204 0.8801 1.1647 1.7224 0.5209
T-Tests Variable Method Variances DF t Value Pr > | t |
Alps Pooled Equal 18 -19.77 <.0001 AIpS Satterthwaite Unequal 16.9 -19.77 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F AIpS Folded F 9 9 1.68 0.4523
Comparison in Osteonectin for Cstitis and KidSton 223
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease K Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctin Cstitis 10 0 .3953 1 .0856 1.7759 0.6638 0.965 1 .7618 0.3052
Onctin KidSton 10 0 .2479 0 .3234 0.3989 0.0726 0.1056 0 .1928 0.0334
Onctin Diff (1-2) 0 .1172 0 .7622 1.4072 0.5187 0.6865 1 .0152 0.307 T-Tests
Variable Method Variances DF t Value Pr > |t|
Onctm Pooled Equal 18 2.48 0 0231
Onctm Satterthwaite Unequal 9 22 2.48 0 0343
Equality of Variances
Variable Method Num DP Den DF F Value Pr > F
Onctm Folded F 9 9 83.54 <.0001
Comparison in Osteonectin for Ostitis and Endoaden 224
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctm Cstitis 10 0.3953 1.0856 1 7759 0.S638 0.965 1 7618 0.3052
Onctm Endoaden 10 0.695 1.1145 1 534 0.4034 0.5864 1.0706 0.1854
Onctm Diff (1-2) -0.779 -0.029 0.7213 0.6034 0.7985 1.1808 0.3571
T-Tests
Variable Method Variances DF t Value Pr > |t|
Onctm Pooled Equal 18 -0 08 0 9364 Onctm Satterthwaite Unequal 14.8 -0.08 0.9366
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctm Folded F 9 9 2 71 0 1539
Comparison in Osteonectin for Cstitis and Prostate
The TTEST Procedure '
Statistics
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctm Cstitis 10 0 .3953 1 .0856 1.7759 0 .6638 0 965 1.7618 0 .3052
Onctm Prostate 10 0 .3309 0 .4352 0.5395 0 .1003 0. 1458 0.2661 0 .0461
Onctm Diff (1-2) 0.002 0 .6504 1.2988 0 .5215 0. 6901 1.0206 0 .3086
T-Tests
Variable Method Variances DF t Value Pr » |t|
Onctm Pooled Equal 18 2.11 0 .0494
Onctm Satterthwaite Unequal 9 .41 2.11 0 .0630
Equality of Variances
Variable Method Num DF Den DF F Value Pr > P
Onctin Folded F 9 9 43.84 <.0001
Comparison m Osteonectin for Cstitis and Prostati
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctm Cstitis 10 0.3953 1 .0856 1 .7759 0 .6638 0 965 1.7618 0.3052
Onctm Prostati 10 0.733 0 .9659 1 .1988 0 .2239 0 .3256 0.5944 0.103
Onctm Diff (1-2) -0.557 0 .1197 0 .7963 0 .5442 0 .7202 1.065 0.3221 T-Tests
Variable Method Variances DF t Value Pr > 111
Onctin Pooled Equal 18 0 37 0 .7145
Onctm Satterthwaite Unequal 11 0 37 0 7172
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctin Folded F 9 9 8 79 0.0034
Comparison in Osteonectin for Ostitis and Arthriti 227
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctin Arthriti 10 1 0861 1.7179 2.3497 0 6074 0.8831 1.6122 0 2793 Onetin Cstitis 10 0.3953 1.0856 1.7759 0 6638 0.965 1.7618 0.3052 Onctin Diff (1-2) -0.237 0.6323 1.5014 0.6989 0.925 1 3679 0.4137
T-Tests
Variable Method Variances DF t Value Pr > |t|
Onctm Pooled Equal 18 1.53 0.1438
Onctin Satterthwaite Unequal 17.9 1 53 0.1439
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctin Folded F 9 9 1.19 0.7959
Comparison in Osteonectin for Cstitis and Aortic
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctin Aortic 10 0.757 0.8917 1 02S4 0.1295 0.1883 0.3438 0 0595
Onctm Cstitis 10 0 3953 1.0856 1.7759 0.6638 0 965 1.7618 0.3052
Onctm Diff (1-2) -0 847 -0.194 0.4593 0.5253 0.6953 1.0282 0 3109
T-Tests
Variable Method Variances t Value Pr > |t|
Onctin Pooled Equal 18 -0.62 0.5407
Onctin Satterthwaite Unequal 9.68 -0.62 0.5473
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctm Folded F 9 9 26.26 <.0001
Comparison m Osteonectin for Cstitis and Parkmso 229
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctm Cstitis 10 0.3953 1 .0856 1.7759 0 .6638 0.965 1.7618 0.3052
Onctin Parkmso 10 2.3631 2 .8852 3.4073 0.502 0 .7298 1.3324 0.2308
Onctm Diff (1-2) -2 603 -1.8 -0.996 0 .6465 0 .8556 1.2652 0.3826 T-Tests
Variable Method Variances DP t Value Pr > |t|
Onctm Pooled Equal 18 -4.70 0.0002
Onetin Satterthwaite Unequal 16.8 -4.70 0.0002
Equality of Variances
Variable Method Num DF Den DP F Value Pr > F
Onctm Folded F 9 9 1.75 0 4179
Comparison in Osteonectin for KidSton and Endoaden
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev std Dev Std Err
Onctm Endoaden 10 0.695 1.1145 1.534 0.4034 0.5864 1 0706 0.1854 Onctm KidSton 10 0.2479 0.3234 0.3989 0.0726 0.1056 0.1928 0.0334 Onctm Diff (1-2) 0.3952 0.7911 1.187 0.3184 0.4213 0.6231 0.1884
T-Tests
Variable Method Variances t Value Pr > |t|
Onctm Pooled Equal 18 4.20 0.0005 Onctm Satterthwaite Unequal 9.58 4.20 0.0020
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctm Folded F 9 9 30.85 <-0001
Comparison m Osteonectin for KidSton and Prostate
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctm KidSton 10 0.2479 0. 3234 0.3989 0 .0726 0.1056 0 .1928 0 .0334
Onctm Prostate 10 0.3309 0. 4352 0.5395 0 .1003 0.1458 0 .2661 0 .0461
Onctm Diff (1-2) -0.231 -0 .112 0.0078 0 .0962 0.1273 0 .1882 0 .0569
T-Tests
Variable Method Variances DF t Value Pr > |t|
Onctm Pooled Equal 18 -1.96 0 .0651 Onctm Satterthwaite Unequal 16.4 -1.96 0 .0667
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctm Folded F 9 9 1.91 0.3507
Comparison m Osteonectin for KidSton and Prostati
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctm KidSton 10 0.2479 0. 3234 0. 3989 0 .0726 0 .1056 0.1928 0.0334
Onctin Prostati 10 0.733 0. 9659 1. 1988 0 .2239 0 .3256 0.5944 0.103
Onctin Diff (1-2) -0.87 -0 .643 -0 .415 0 .1829 0.242 0.3579 0.1082 T-Tests
Variable Method Variances DF t Value Pr > |t|
Onctin Pooled Equal 18 -5.94 <.0001
Onctin Satterthwaite Unequal 10.9 -5.94 0.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctin Folded F 9 9 9.51 0.0025
Comparison in Osteonectin for KidSton and Arthriti 233
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctm Arthriti 10 1. .08Sl 1 .7179 2.3497 0 .6074 0.8831 1.6122 0.2793
Onctin KidSton 10 0. .2479 0 .3234 0.3989 0 .0726 0.1056 0.1928 0.0334
Onctin Diff (1-2) 0. .8036 1 .3945 1.9854 0 .4752 0.6289 0.9301 0.2813
T-Tests
Variable Method Variances DF t Value Pr
Figure imgf000466_0001
Onctin Pooled Equal 18 4.96 0.0001
Onctin Satterthwaite Unequal 9 .26 4.96 0.0007
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctin Folded F 9 9 69.96 <.0001
Comparison in Osteonectin for KidSton and Aortic 234
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev std Err
Onctm Aortic 10 0.757 0 .8917 1.0264 0 .1295 0.1883 0.3438 0.0595
Onctin KidSton 10 0.2479 0 .3234 0.3989 0 .0726 0.1056 0.1928 0.0334
Onctin Diff (1-2) 0.4249 0 .5683 . 0.7117 0 .1153 0.1527 0.2258 0.0683
T-Tests
Variable Method Variances DF t Value
Onctin Pooled Equal 18 8.32 <.0001
Onctin Satterthwaite Unequal 14 .1 8.32 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctin Folded F 9 9 3.18 0.0998
Comparison in Osteonectin for KidSton and Parkinso 235
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctin KidSton 10 0. 2479 0.3234 0. 3989 0. 0726 0 .1056 0.1928 0.0334
Onctin Parkinso 10 2. 3631 2.8852 3. 4073 0 .502 0 .7298 1.3324 0.2308
Onctin Diff (1-2) -3 .052 -2.562 —2 .072 0 .394 0 .5214 0.7711 0.2332 T-Tests
Variable Method Variances DF t Value Pr > |t|
Onctin Pooled Equal 18 -10.99 <.0001
Onctin Satterthwaite Unequal 9.38 -10.99 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctin Folded F 9 9 47.78 <.0001
Comparison in Osteonectin for Endoaden and Prostate 236
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctin Endoaden 10 0.695 1.1145 1.534 0.4034 0.5864 1.0706 0.1854
Onctin Prostate 10 0.3309 0.4352 0.5395 0.1003 0.1458 0.2661 0.0461
Onctin Diff (1-2) 0.2778 0.6793 1.0808 0.3229 0.4273 0.6319 0.1911
T-Tests
Variable Method Variances DF t Value Pr > |t|
Onctin Pooled Equal 18 3.55 0.0023 Onctin Satterthwaite Unequal 10.1 3.55 0.0051
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctin Folded F 9 9 16.19 0.0003
Comparison in Osteonectin for Endoaden and Prostati 237
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctin Endoaden 10 0.695 1 .1145 1.534 0.4034 0.5864 1.0706 0.1854
Onctin Prostati 10 0.733 0 .9659 1.1988 0.2239 0.3256 0.5944 0.103
Onctin Diff (1-2) -0.297 0 .1486 0.5942 0.3584 0.4743 0.7014 0.2121
T-Tests
Variable Method Variances t Value Pr > |t|
Onctin Pooled Equal 18 0.70 0.4925 Onctin Satterthwaite Unequal 14.1 0.70 0.4950
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctin Folded F 9 9 3.24 0.0945
Comparison in Osteonectin for Endoaden and Arthriti 238
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctin Arthriti 10 1.0861 1 .7179 2.3497 0.6074 0 .8831 1.6122 0.2793
Onctin Endoaden 10 0.695 1 .1145 1.534 0.4034 0 .5864 1.0706 0.1854
Onctin Diff (1-2) -0.101 0 .6034 1.3077 0.5664 0 .7496 1.1085 0.3352 T-Tests
Variable Method Variances DF t Value Pr > |t|
Onctm Pooled Equal 18 1 80 0 0887
Onctin Satterthwaite Unequal 15 6 1 80 0 0912
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctin Folded F 9 9 2 27 0 2384
Comparison m Osteonectin for Endoaden and Aortic 239
The TTEST Procedure Statistics
Lower CIJ Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onetin tic 10 0 757 0 8917 1 0264 0 1295 0 1883 0 3438 0 0595 Onctin oaden 10 0 695 1 1145 1 534 0 4034 0 5864 1 0706 0 1854 Onctm f (1-2) -0 632 -0 223 0 1864 0 3291 0 4355 0 6441 0 1948
T-Tests
Variable Method Variances DF t Value Pr > |t|
Onctm Pooled Equal 18 -1 14 0 2676
Onctm Satterthwaite Unequal 10 8 -1 14 0 2773
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctm Folded F 9 9 9 70 0 0023
Comparison in Osteonectin for Endoaden and Parkmso 240
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctm Endoaden 10 0 695 1 1145 1 534 0 4034 0 5864 1 0706 0 1854
Onctm Parkmso 10 2 3631 2 8852 3 4073 0 502 0 7298 1 3324 0 2308
Onctm Diff (1-2) -2 393 -1 771 -1 149 0 5002 0 662 0 979 0 2961
T-Tests
Variable Method Variances t Value Pr > |t|
Onctm Pooled Equal 18 -5 98 0001 Onctm Satterthwaite Unequal 17 2 -5 98 0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctm Folded F 9 9 1 55 0 5248
Comparison in Osteonectin for Prostate and Prostati 241
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctm Prostate 10 0 3309 0 4352 0 5395 0 1003 0 1458 0 2661 0 0461
Onctin Prostati 10 0 733 0 9659 1 1988 0 2239 0 3256 0 5944 0 103
Onctm Diff (1-2) -0 768 -0 531 -0 294 0 1906 0 2522 0 373 0 1128 T-Tests
Variable Method Varxances DF t Value Pr > |t|
Onctm Pooled Equal IS -4 70 0 .0002
Onctm Satterthwaite Unequal 12.5 -4 70 0 0005
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctm Folded F 9 9 4 99 o 0252
Comparison in Osteonectin for Prostate and Arthriti 242
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctm Arthriti 10 1 0851 1.7179 2.3497 0.6074 0.8831 1.6122 0 2793 Onctm Prostate 10 0.3309 0.4352 0.S395 0.1003 0.14S8 0.2661 0.0461 Onctm Diff (1-2) 0.688 1.2827 1.8774 0.4782 0.6329 0 93S 0 283
T-Tests
Variable Method Variances DF t Value Pr > |t|
Onctin Pooled Equal 18 4.53 0 0003 Onctm Satterthwaite Unequal 9 49 4.53 0 0012
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctm Folded F 9 9 36 71 <.0001
Comparison in Osteonectin for Prostate and Aortic 243
The TTEST Procedure Statistics
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctm Aortic 10 0.757 0 .8917 1. .0264 0 1295 0.1883 0.3438 0 .0595
Onctm Prostate 10 0.3309 0 .4352 0. .5395 0 1003 0.1458 0 2661 0 .0461
Onctm Diff (1-2) 0.2983 0 .4565 0. .6147 0 .1272 0.1684 0 249 0 .0753
T-Tests
Variable Method Variances DF t Value Pr > |t|
Onctm Pooled Equal 18 6.06 < .0001
Onctm Satterthwaite Unequal IS.9 6.06 < 0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctm Folded F 9 9 1.67 0.4572
Comparison xn Osteonectin for Prostate and Parkmso 244
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctin Parkmso 10 2 .3631 2 8852 3 .4073 0.502 0. 7298 1.3324 0.2308
Onctm Prostate 10 0 .3309 0 .4352 0 .5395 0.1003 0. 1458 0.2661 0.0461
Onctm Diff (1-2) 1 .9555 2.45 2 .9445 0.3977 0. 5263 0.7783 0.2354 T-Tests
Variable Method Variances DF t Value Pr > |t|
Onehin Pooled Equal 18 10.41 <.0001 Onctin Satterthwalte Unequal 9.72 10.41 <-0001
Equality of Variances
Variable Method Nutn DF Den DF F Value Pr > F
Onctin Folded F 9 9 25.07 <.0001
Comparison in Osteonectin for Prostati and Arthriti
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctin Arthriti 10 1.08S1 1 .7179 2.3497 0.S074 0.8831 1.S122 0.2793
Onctin Prostati 10 0.733 0 .9659 1.1988 0.2239 0.3256 0.5944 0.103
Onctin Diff (1-2) 0.12S7 0.752 1.3773 0.5029 0.6655 0.9842 0.297S
T-Tests
Variable Method Variances t Value Pr > |t|
Onctin Pooled Equal 18 2.53 0.0211 Onctin Satterthwaite Unequal 11.4 2.53 0.0275
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctin Folded F 9 9 7.36 O.OOSS
Comparison in Osteonectin for Prostati and Aortic 246
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctin Aortic 10 0.757 0. 8917 1.0264 0.1295 0. 1883 0.3438 0.0595
Onctin Prostati 10 0.733 0. 9659 1.1988 0.2239 0. 3256 0.5944 0.103
Onctin Diff (1-2) -0.324 -0 .074 0.1757 0.201 0 .266 0.3933 0.1189
T-Tests
Variable Method Variances DF t Value Pr > |t|
Onctin Pooled Equal 18 -0 .62 0.5405
Onctin Satterthwaite Unequal 14.4 -0 .62 0.5425
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctin Folded F 9 9 2.99 0.1185
Comparison in Osteonectin for Prostati and Parkinso
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev std Err
Onctm Parkmso 10 2 .3631 2 .8852 3 .4073 0 .502 0 .7298 1.3324 0.2308
Onctin Prostati 10 0.733 0 .9659 1 .1988 0. 2239 0 .3256 0.5944 0.103
Onctin Diff (1-2) 1 .3884 1 .9193 2 .4502 0 .427 0 .5651 0.8357 0.2527 T-Tests
Variable Method Variances DF t Value Pr > |t|
Onctin Pooled Equal 18 7 59 <.0001
Onctm Satterthwaite Unequal 12 4 7.59 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctm Folded F 9 9 5 03 0.0247
Comparison in Osteonectin for Arthriti and Aortic 248
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctm tic 10 0.757 0. 8917 1 0264 0 .1295 0.1883 0.3438 0 .0595 Onctm hπti 10 1.08S1 1. 7179 2.3497 0 .6074 0.8831 1 6122 0 .2793 Onctm f (1-2) 1 426 -0 .826 -0 226 0 .4825 0.6385 0 9442 0 .2855
T-Tests
Variable Method Variances DF t Value Pr > |t|
Onctm Pooled Equal 18 -2.89 0 .0097
Onctm Satterthwaite Unequal 9 82 -2.89 0 .0163
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctin Folded F 9 9 21.99 < 0001
Comparison in Osteonectin for Arthriti and Parkmso 249
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctin hnti 10 1 0861 1.7179 2.3497 0 .6074 0. 8831 1.6122 0 2793 Onctm kmso 10 2. .3631 2.8852 3 4073 0.502 0. 7298 1.3324 0 .2308 Onctm f (1-2) -: L.928 -1.167 -0 406 0 .6121 0. 8101 1.198 0 .3623
T-Tests
Variable Method Variances DF t Value Pr > ]t|
Onctin Pooled Equal 18 -3.22 0 0047
Onctm Satterthwaite Unequal 17.4 -3 22 0 .0049
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctm Folded F 9 9 1.46 0.5791
Comparison in Osteonectin for Aortic and Parkmso 250
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Onctm Aortic 10 0.757 0.8917 1. 0264 0 .1295 0 .1883 0 .3438 0 .0595
Onctm Parkmso 10 2.3631 2.8852 3. 4073 0.502 0 .7298 1 .3324 0 .2308
Onctm Diff (1-2) -2.494 -1.994 -1 .493 0 .4027 0.533 0 .7882 0 .2384 T-Tests
Variable Method Variances DF t Value Pr > |t|
Onctin Pooled Equal 18 -S.36 <.0001
Onctin Satterthwaite Unequal 10.2 -S.3S <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Onctin Folded F 9 9 15.02 0.0004
Comparison in Osteocalcin for Cstitis and KidSton 251
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcin Cstitis 10 5 .1478 10 .123 15.098 4 .7838 6 .9549 12.697 2.1993 Olcin KidSton 10 0 .0399 0. 1364 0.2329 0 .0927 0 .1348 0.2462 0.0426 Olcin Diff (1-2) 5 .3651 9. 9866 14.608 3 .7167 4 .9187 7.274 2.1997
T-Tests
Variable Method Variances t Value Pr > |t|
Olcin Pooled Equal 18 4.54 0.0003 Olcin Satterthwaite Unequal 9.01 4.54 0.0014
Equality of Variances
Variable Method Num DE Den DF F Value Pr > F
Olcin Folded F 9 9 2660.35 <.0001
Comparison in Osteocalcin for Cstitis and Endoaden
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev std Err
Olcin itis 10 5 .1478 10.123 15 .098 4 .7838 6.9549 12.697 2 .1993 Olcin oaden 10 1 .6763 2.7105 3. 7447 0 .9944 1.4457 2.6393 0 .4572 Olcin f (1-2) 2 .6931 7.4125 12 .132 3 .7954 5.023 7.4281 2 .2463
T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcin Pooled Equal 18 3.30 0 .0040
Olcin Satterthwaite Unequal 9 .78 3.30 0 .0083
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcin Folded F 9 9 23.14 <.0001
Comparison in Osteocalcin for Cstitis and Prostate
The TTEST Procedure
Statistics
Lower CL Upper CL jower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcin Cstitis 10 5.1478 10 .123 15.098 4.7838 6.9549 12.697 2.1993
Olcin Prostate 10 0 0 0 0 0
Olcin Diff (1-2) 5.5024 10 .123 14.744 3.716 4.9178 7.2726 2.1993 T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcm Pooled Equal 18 4 60 0 0002 Olcm Satterthwaite Unequal 9 4 60 0 0013
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > P
Olcin Folded F 9 9 Infty < 0001
Comparison in Osteocalcin for Cstitis and Prostati
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Cstitis 10 5. .1478 10 .123 15 098 4 7838 6.9549 12.697 2 1993
Olcm Prostati 10 1 5289 2 1122 2. 6955 0 5609 0.8154 1.4886 0 2579
Olcm Dlff (1-2) 3. .3586 8. 0108 12 663 3 .7414 4.9515 7 3224 2.2144
T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcm Pooled Equal 18 3. .62 0.0020
Olcm Satterthwaite Unequal 9 25 3. .62 0.0053
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcm Folded F 9 9 72 75 < 0001
Comparison m Osteocalcin for Cstitis and Arthriti 255
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Arthriti 10 6.2895 10 713 15 .136 4 2532 6.1835 11.289 1 .9554
Olcin Cstitis 10 5.1478 10 123 15 .098 4 .7838 6.9549 12 697 2 .1993
Olcin Diff (1-2) -5.593 0. 5899 6. 7727 4 .9723 6.5805 9.7314 2 .9429
T-Tests
Variable Method Variances DF t Value Pr » It
Olcin Pooled Equal 18 0 20 0 .8434
Olcm Satterthwaite Unequal 17 8 0.20 0 8434
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcm Folded F 9 9 1.27 0.7319
Comparison m Osteocalcin for Cstitis and Aortic 256
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Aortic 10 3.7596 4.3479 4 9362 0.5656 0.8223 1.5013 0.26 Olcm Cstitis 10 5.1478 10.123 15.098 4.7838 6.9549 12.697 2.1993 Olcin Dlff (1-2) -10.43 -5.775 -1.122 3.7419 4.9521 7.3233 2.2146 T-Tests
Variable Method Variances DF t Value Pr > ItI
Olcin Pooled Equal 18 -2.61 0 .0178 Olcin Satterthwaite Unequal 9.25 -2.Sl 0.0278
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcin Folded F 9 9 71.53 <.0001
Comparison in Osteocalcin for Ostitis and Parkinso 257
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcin Ostitis 10 5 .1478 10 .123 15 .098 4 .7838 S.9549 12.697 2.1993 Olcin Parkinso 10 2.1237 2.5S6S 3.0095 0.4259 0.6192 1.1304 0.1958 Olcin Diff (1-2) 2.9175 7.5564 12.195 3.7307 4.9373 7.3014 2.208
T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcin Pooled Equal 18 3.42 0.0030 Olcin Satterthwaite Unequal 9.14 3.42 0.0074
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcin Folded F 9 9 126.16 <.0001
Comparison in Osteocalcin for KidSton and Endoaden 258
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcin Endoaden 10 1 .6763 2 .7105 3.7447 0 .9944 1.4457 2.6393 0.4572 Olcin KidSton 10 0.0399 0.1364 0.2329 0.0927 0.1348 0.2462 0.0426 Olcin Diff (1-2) 1.6094 2.5741 3.5388 0.7758 1.0267 1.5183 0.4592
T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcin Pooled Equal 18 5.61 <,0001 Olcin Satterthwaite Unequal 9.16 5.61 0.0003
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcin Folded F 9 9 114.96 <.0001
Comparison in Osteocalcin for KidSton and Prostate 259
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev std Dev Std Err
Olcin KidSton 10 0 .0399 0 .1364 0.2329 0.0927 0 .1348 0.2462 0 .0426
Olcin Prostate 10 0 0 0 0 0
Olcin Diff (1-2) 0 .0468 0 .1364 0.226 0.072 0 .0953 0.141 0 .0426 T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcm Pooled Equal 18 3 20 0.0050
Olcm Satterthwaite Unequal 9 3.20 0.0109
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcin Folded F 9 9 Infty <.0001
Comparison in Osteocalcin for KidSton and Prostati
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm KidSton 10 0.0399 0. 1364 0. 2329 0 .0927 0. 1348 0 2462 0 .0426 Olcm Prostati 10 1.5289 2. 1122 2. 5955 0 .5509 0. 8154 1.4886 0 .2579 Olcm Diff (1-2) -2.525 -1 .97S -1 .427 0 .4416 0. 5844 0.8643 0 .2614
T-Tests
Variable Method Variances DF t Value Pr » It
Olcm Pooled Equal 18 -7.56 < .0001 Olcm Satterthwaite Unequal 9 .49 -7.56 < .0001
Equality of Variances
Variable Method Num DF Den DF P Value Pr > F
Olcin Folded F 9 9 36.57 <.0001
Comparison in Osteocalcin for KidSton and Arthπti 261
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Arthriti 10 6. 2895 10 .713 15.136 4.2532 6.1835 11.289 1.9554
Olcin KidSton 10 0. 0399 0. 1364 0.2329 0.0927 0.1348 0.2462 0.0426
Olcm Diff (1-2) 6. 4674 10 .577 14.686 3.3046 4.3734 6.4675 1.9558
T-Tests
Variable Method Variances t Value Pr >
Olcm Pooled Equal 18 5.41 <.0001 Olcin Satterthwaite Unequal 9.01 5.41 0.0004
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcin Folded F 9 9 2102.94 <.0001
Comparison m Osteocalcin for KidSton and Aortic 262
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcin Aortic 10 3.7596 4.3479 4 .9362 0 .5656 0 .8223 1 .5013 0.26 Olcin KidSton 10 0.0399 0.1364 0 .2329 0 .0927 0 .1348 0 .2462 0 .0426 Olcin Diff (1-2) 3 .6579 4 .2115 4 .7651 0 .4452 0 .5892 0 .8714 0 .2635 T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcm Pooled Equal 18 15 98 ■=.0001
Olcm Satterthwaite Unequal 9 48 15.98 < 0001
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
Olcm Folded F 9 9 37 19 < 0001
Comparison in Osteocalcin for Kidston and Parkmso 263
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm KidSton 10 0.0399 0.13S4 0.2329 0 .0927 0.1348 0 2462 0 0426 Olcm Parkmso 10 2 1237 2 SS66 3.0095 0.4259 0.6192 1 1304 0 1958 Olcm Diff (1-2) -2 851 -2 43 -2.009 0.3386 0.4481 0 6627 0 2004
T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcm Pooled Equal 18 -12 .13 < 0001 Olcm Satterthwaite Unequal 9.85 -12.13 <.0001
Equality of Variances
Variable Method Num DF Den DP F Value Pr > F
Olcm Folded F 9 9 21 09 0 0001
Comparison in Osteocalcin for Endoaden and Prostate
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Endoaden 10 1 .6763 2 .7105 3.7447 0 9944 1.4457 2.6393 0.4572
Olcm Prostate 10 0 0 0 0 0
Olcm Diff (1-2) 1.75 2 .7105 3 671 0.7725 1.0223 1.5118 0.4572
T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcm Pooled Equal 18 5 93 <.0001 Olcm Satterthwaite Unequal 9 5 93 0.0002
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcm Folded F 9 9 Infty <.0001
Comparison in Osteocalcin for Endoaden and Prostati 265
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Endoaden 10 1.6763 2.7105 3 .7447 0 .9944 1 .4457 2 .6393 0 .4572
Olcm Prostati 10 1.5289 2.1122 2 .6955 0 .5609 0 .8154 1 .4886 0 .2579
Olcm Diff (1-2) -0.504 0.5983 1.701 0 .8868 1 .1737 1 .7357 0 .5249 T-Tests
Variable Method Variances DF t Value Pr > lt|
Olcm Pooled Equal 18 1.14 0 .2693
Olcm Satterthwaite Unequal 14.2 1 14 0 .2732
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
Olcm Folded F 9 9 3 14 0.1032
Comparison in Osteocalcin for Endoaden and Arthriti 266
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Arthriti 10 6 .2895 10.713 15.136 4 2532 6.1835 11.289 1. 9554
01cm Endoaden 10 1 .6763 2.7105 3.7447 0 .9944 1.4457 2.6393 0. 4572
01cm Diff (1-2) 3 .7835 8.0024 12.221 3 .3929 4.4903 6.6403 2. 0081
T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcm Pooled Equal 18 3.99 0.0009
Olcm Satterthwaite Unequal 9 .98 3.99 0.0026
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcm Folded F 9 9 18.29 0.0002
Comparison in Osteocalcin for Endoaden and Aortic 267
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Aortic 10 3 .7596 4.3479 4.9362 0.5656 0.8223 1.5013 0.26 Olcm Endoaden 10 1 .6763 2.7105 3.7447 0.9944 1.4457 2.6393 0.4572 Olcin Diff (1-2) 0 .5324 1.6374 2.7424 0.8887 1.1761 1.7392 0.526
T-Tests
Variable Method Variances DF t Value Pr |t|
Olcm Pooled Equal 18 3.11 0.0060 Olcm Satterthwaite Unequal 14.3 3.11 0.0075
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcin Folded F 9 9 3.09 0.1081
Comparison in Osteocalcin for Endoaden and Parkmso 268
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Endoaden 10 1. 6763 2 .7105 3 .7447 0 .9944 1 .4457 2 .6393 0 .4572
Olcm Parkmso 10 2. 1237 2 .5666 3 .0095 0 .4259 0 .6192 1 .1304 0 .1958
Olcm Diff (1-2) -0 .901 0 .1439 1 .1888 0 .8403 1 .1121 1 .6446 0 .4973 T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcm Pooled Equal 18 0.29 0 7756 Olcm Satterthwaite Unequal 12 2 0 29 0.7772
Equality of Variances
Variable Method Nurn DF Den DF F Value Pr > F
Olcm Folded F 9 9 5.45 0 0188
Comparison m Osteocalcin for Prostate and Prostati 269
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Prostate 10 0 0 0 0 0 Olcm Prostati 10 1.5289 2.1122 2.6955 0 5609 0 8154 1.4886 0.2579 Olcm Dlff (1-2) -2.654 -2.112 -1.57 0 4357 0 5766 0.8527 0 2579
T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcm Pooled Equal 18 -! 3 19 <.0001 Olcm Satterthwaite Unequal 9 -S3.19 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcm Folded F 9 9 Infty <.0001
Comparison m Osteocalcin for Prostate and Arthriti 270
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Arthriti 10 6 2895 10.713 15. .136 4.2532 6.: L835 11 289 1 9554
Olcin Prostate 10 0 0 0 0 0
Olcm Dlff (1-2) 6 S048 10.713 14 821 3.3038 4.3724 6.466 1. 9554
T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcm Pooled Equal 18 5.48 <.0001
Olcm Satterthwaite Unequal 9 5.48 0.0004
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcm Folded F 9 9 Infty <.0001
Comparison m Osteocalcin for Prostate and Aortic 271
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Aortic 10 3 .7596 4 .3479 4 9362 0.5656 0 .8223 1 .5013 0 .26
Olcm Prostate 10 0 0 0 0 0
Olcm Dlff (1-2) 3 .8016 4 .3479 4 .8942 0.4394 0 .5815 0 .8599 0 .26 T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcm Pooled Equal 18 IS 72 0001
Olcin Satterthwaxte Unequal 9 16 72 < 0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcm Folded F 9 9 Infty <.0001
Comparison m Osteocalcin for Prostate and Parkmso
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Parkmso 10 2 1237 2 5666 3 0095 0.4259 0 6192 1 1304 0.1958
Olcm Prostate 10 0 0 0 0 0
Olcm Dlff (1-2) 2 .1552 2 .5666 2.978 0.3308 0 4378 0.6475 0.1958
T-Tests
Variable Method Variances DF t Value Pr > It
Olcm Pooled Equal 18 13 .11 < .0001 Olcm Satterthwaite Unequal 9 13 .11 < .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcm Folded F 9 9 Infty < 0001
Comparison m Osteocalcin for Prostati and Arthπti 273
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Arthπti 10 6.2895 10 .713 15 .136 4 .2532 6 .1835 11 289 1.9554 Olcm Prostati 10 1.5289 2. 1122 2 6955 0 5609 0 .8154 1.4886 0 2579 Olcm Diff (1-2) 4 457 8. 6007 12 .744 3 .3324 4 .4102 6.5219 1.9723
T-Tests
Variable Method Variances DF t Value Pr |t|
Olcm Pooled Equal 18 4.36 0.0004 Olcm Satterthwaite Unequal 9.31 4.36 0.0017
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcm Folded F 9 9 57.50 <.0001
Comparison m Osteocalcin for Prostati and Aortic 274
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcin Aortic 10 3 .7596 4 .3479 4 .9362 0 .5656 0 8223 1.5013 0.26 Olcin Prostati 10 1 .5289 2 .1122 2 .6955 0 .5609 0 8154 1.4886 0.2579 Olcm Diff (1-2) 1 .4663 2 .2357 3 .0051 0 .6188 0 .8189 1.211 0.3662 T-Tests
Variable Method Variances DF t Value Pr > 11
Oicin Pooled Equal 18 S.10 <-0001
01cm Satterthwaite Unequal 18 6.10 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
01cm Folded F 9 9 1.02 0.9803
Comparison in Osteocalcin for Prostati and Parkmso 275
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
01cm Parkmso 10 2 .1237 2 .5666 3.0095 0 .4259 0. 6192 1.1304 0 .1958
01cm Prostati 10 1 .5289 2 .1122 2.6955 0 .5609 0. 8154 1.4886 0 .2579
Olcm Diff (1-2) - 0.226 0 .4544 1.1346 0 .5471 0 .724 1.0706 0 .3238
T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcm Pooled Equal 18 1.40 0 .1775
Olcm Satterthwaite Unequal 16.8 1.40 0 .1787
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcm Folded F 9 9 1.73 0.4246
Comparison m Osteocalcin for Arthπti and Aortic 276
The TTEST Procedure
Statistics
Lower CL Upper CL jower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Aortic 10 3.7596 4.3479 4.9362 0.5656 0.8223 1.5013 0.26
Olcm Arthriti 10 6.2895 10.713 15.136 4.2532 6.1835 11.289 1.9554
Olcm Diff (1-2) -10.51 -6.3S5 -2.221 3.3329 4.4109 6.5229 1.9726
T-Tests
Variable Method Variances t Value Pr > |t|
Olcm Pooled Equal 18 -3.23 0.0047 Olcm Satterthwaite Unequal 9.32 -3.23 0.0099
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Olcm Folded F 9 9 56.54 <.0001
Comparison in Osteocalcin for Arthriti and Parkmso
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Std Dev Std Dev Std Dev Std Err
Olcm Arthriti 10 6. .2895 10 .713 15.136 4 .2532 6.1835 11 .289 1 .9554 Olcm Parkmso 10 2. .1237 2 .5666 3 .0095 0 .4259 0 .6192 1 .1304 0 .1958 Olcm Diff (1-2 ) 4 .0176 8 .1463 12 .275 3 .3203 4 .3942 6 .4983 1 .9652 T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcxn Pooled Equal 18 4.15 0 .0006
01cm Ξatterthwaite Unequal 9.18 4.15 0 .0024
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
01cm Folded F 9 9 99.73 -=.0001
Comparison m Osteocalcin for Aortic and Parkmso 278
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
01cm Aortic 10 3 .7595 4 .3479 4.9362 0 .5656 0.8223 1.50 0.2S
Olcin Parkmso 10 2 .1237 2 .5666 3.0095 0 .4259 0.6192 1.13 0.1958
01cm Diff (1-2) 1 .0974 1 .7813 2.4652 0.55 0.7279 1.07 0.3255
T-Tests
Variable Method Variances DF t Value Pr > |t|
Olcin Pooled Equal 18 5 47 < .0001
01cm Satterthwaite Unequal 16.7 5.47 < .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
01cm Folded F 9 9 1.76 0.4107
Comparison in Troponin C for Cstitis and KidSton 279
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Cstitis 10 0.1043 0 .7169 1.3295 0.5891 0.8564 1.5635 0.2708
TroC KidSton 10 -0.034 0 .0653 0.165 0.09S9 0.1394 0.2545 0.0441
TroC Diff (1-2) 0.0751 0 .6516 1.2281 0.4636 0.6135 0.9073 0.2744
T-Tests
Variable Method Variances t Value Pr > |t|
TroC Pooled Equal 18 2.37 0.0289 TroC Satterthwaite Unequal 9.48 2.37 0.0403
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 37.74 <.0001
Comparison m Troponin C for Cstitis and Endoaden 280
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Cstitis 10 0.1043 0. 7169 1 .3295 0 .5891 0 .8564 1.5635 0.2708
TroC Endoaden 10 0.5658 0. 9502 1 .3346 0 .3696 0 .5373 0.9809 0.1699
TroC Diff (1-2) -0.905 -0 .233 0 .4384 0 .5402 0 .7149 1.0572 0.3197 T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 -0.73 0.4749 TroC Satterthwaite Unequal 15.1 -0.73 0.4767
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 2.54 0.1811
Comparison in Troponin C for Ostitis and Prostate 281
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Cstitis 10 0.1043 0.7169 1.3295 0.5891 0.8564 1.5635 0.2708
TroC Prostate 10 -0.048 0.1119 0.2717 0.1536 0.2234 0.4078 0.0706
TroC Diff (1-2) 0.017 0.605 1.193 0.4729 0.6258 0.9255 0.2799
T-Tests
Variable Method Variances t Value Pr > |t|
TroC Pooled Equal 18 2.16 0.0444 TroC Satterthwaite Unequal 10.2 2.16 0.0554
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 14 70 0.0005
Comparison in Troponin C for Cstitis and Prostati
The TTEST Procedure Statistics
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Cstitis 10 0.1043 0 .7169 1.3295 0. 5891 0.8564 1.5635 0. 2708
TroC Prostati 10 0.441 0 .6432 0.8454 0. 1944 0.2827 0.5161 0. 0894
TroC Diff (1-2) -0.525 0 .0737 0.6729 0. 4819 0.6377 0.943 0. 2852
T-Tests
Variable Method Variances DF t Value Pr > It=I
TroC Pooled Equal 18 0.26 0 .7990
TroC Satterthwaite Unequal 10.9 0.26 0 .8009
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 9.18 0.0029
Comparison in Troponin C for Cstitis and Arthriti
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Arthriti 10 0.3642 0.9682 1 .5722 0 .5807 0 .8443 1 .5414 0.267
TroC Cstitis 10 0.1043 0.7169 1 .3295 0 .5891 0 .8564 1 .5635 0 .2708
TroC Diff (1-2) -0.548 0.2513 1 .0503 0 .6426 0 .8504 1 .2576 0 .3803 T-Tests
Variable Method Variances DF t Value Pr > ItI
TroC Pooled Equal 18 0.66 0 5171
TroC Satterthwaite Unequal 18 0.66 0 5171
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 1.03 0 9669
Comparison m Troponin C for Ostitis and Aortic 284
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC tic 10 0, .0721 0. 2331 0.3941 0. 1548 0 2251 0.4109 0.0712 TroC ltlS 10 0 1043 0 7169 1.3295 0 5891 0 8564 1 5635 0.2708 TroC f (1-2) -1.072 -0 484 0.1045 0 4731 0 6261 0.9259 0.28
T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 -1.73 0 .1011
TroC Satterthwaite Unequal 10.2 -1.73 0 .1140
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 14 48 0.0005
Comparison in Troponin C for Ostitis and Parkmso 285
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Ostitis 10 0 1043 0 7169 1.3295 0 .5891 0.8564 1.5635 0.2708 TroC Parkmso 10 2 3304 2 547 2 7636 0.2082 0.3027 0.5527 0.0957 TroC Dlff (1-2) Ϊ.434 -1.83 -1.227 0 4853 0.6423 0.9498 0.2872
T-TestS
Variable Method Variances DF t Value
TroC Pooled Equal 18 -6 37 <.0001 TroC Satterthwaite Unequal 11.2 -6..37 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 8.00 0.0048
Comparison in Troponin C for KidSton and Endoaden 286
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Endoaden 10 0. 5658 0 .9502 1 .3346 0 .3696 0 .5373 0 .9809 0 .1699
TroC KidSton 10 -0 .034 0 .0653 0.165 0 .0959 0 .1394 0 .2545 0 .0441
TroC Dlff (1-2) 0. 5161 0 .8849 1 .2537 0 .2966 0 .3925 0 .5805 0 .1755 T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 S.04 <.0001
TroC Satterthwaite Unequal 10.2 5.04 0.0005
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 14.86 0.0004
Comparison in Troponin C for KidSton and Prostate
The TTEST Procedure Statistics
Lower CL . Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC KidSton 10 -0.034 0. 0S53 0.165 0. .0959 0.1394 0.2545 0. 0441
TroC Prostate 10 -0.048 0. 1119 0.2717 0. .1536 0.2234 0.4078 0. 0706
TroC Diff (1-2) -0.222 -0 .047 0.1283 0 .1407 0.1862 0.2753 0. 0833
T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 -0.56 0.5826
TroC Satterthwaite Unequal 15.1 -0.56 0.5839
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 2.57 0.1764
Comparison in Troponin C for KidSton and Prostati 288
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC KidSton 10 -0 .034 0. 0653 0.165 0.0959 0.1394 0.2545 0.0441
TroC Prostati 10 0 .441 0. 6432 0.8454 0.1944 0.2827 0.5161 0.0894
TroC Diff (1-2) -0 .787 -0 .578 -0.369 0.1684 0.2229 0.3296 0.0997
T-Tests
Variable Method Variances DP t Value
TroC Pooled Equal 18 -5.80 <-0001 TroC Satterthwaite Unequal 13.1 -5.80 ■=.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 4.11 0.0468
Comparison in Troponin C for KidSton and Arthriti
The TTEST Procedure Statistics
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Arthriti 10 0. 3642 0 .9682 1.5722 0 .5807 0. 8443 1. 5414 0.267
TroC KidSton 10 -0 .034 0 .0653 0.165 0 .0959 0. 1394 0. 2545 0.0441
TroC Diff (1-2) 0. 3344 0 .9029 1.4714 0, .4572 0. 6051 0. 8948 0.2706 T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 3.34 0.0037
TroC Satterthwaite Unequal 9.49 3.34 0.0081
Equality of Variances
Variable Method Num DP Den DF F Value Pr > F
TroC Folded F 9 9 36.69 <.0001
Comparison in Troponin C for KidSton and Aortic 290
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Aortic 10 0. 0721 0 .2331 0.3941 0.1548 0.2251 0.4109 0.0712
TroC KidSton 10 -0 .034 0 .0653 0.165 0.0959 0.1394 0.2545 0.0441
TroC Diff (1-2) -0 .008 0 .1678 0.3437 0.1415 0.1872 0.27S8 0.0837
T-Tests
Variable Method Variances t Value Pr > |t|
TroC Pooled Equal 18 2.00 0.0603 TroC Satterthwaite Unequal 15 2.00 0.0634
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 2.61 0.1697
Comparison in Troponin C for KidSton and Parkinso
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC KidSton 10 -0.034 0.0653 0.165 0.0959 0.1394 0.2545 0.0441
TroC Parkinso 10 2.3304 2.547 2.7636 0.2082 0.3027 0.5527 0.0957
TroC Diff (1-2) -2.703 -2.482 -2.26 0.1781 0.2357 0.3485 0.1054
T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 -23.55 < .0001 TroC Satterthwaite Unequal 12.7 -23.55 .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 4.72 0.0303
Comparison in Troponin C for Endoaden and Prostate 292
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Endoaden 10 0. 5S58 0 .9502 1 .3346 0.3696 0 .5373 0 .9809 0 .1699
TroC Prostate 10 -0 .048 0 .1119 0 .2717 0.1536 0 .2234 0 .4078 0 .0706
TroC Diff (1-2) 0. 4517 0 .8383 1 .2249 0.3109 0 .4115 0 .6085 0.184 T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 4.56 0.0002
TroC Satterthwaite Unequal 12 4.56 0.0007
Equality of Variances
Variable Method Num DF Den DF F.Value Pr > F
TroC Folded F 9 9 5.79 0.0153
Comparison in Troponin C for Endoaden and Prostati 293
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Endoaden 10 0.5658 0 .9502 1. 3346 0 .3696 0.5373 0.9809 0.1699
TroC Prostati 10 0.441 0 .6432 0. 8454 0 .1944 0.2827 0.5161 0.0894
TroC Diff (1-2) -0.096 0.307 0. 7104 0 .3244 0.4293 0.6349 0.192
T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 1.60 0 .1272
TroC Satterthwaite Unequal 13.6 1.60 0 .1327
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 3.61 0.0692
Comparison in Troponin C for Endoaden and Arthriti 294
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Arthriti 10 0.3642 0.9682 1.5722 0.5807 0.8443 1.5414 0.267
TroC Endoaden 10 0.5658 0.9502 1.3346 0.3696 0.5373 0.9809 0.1699
TroC Diff (1-2) -0.647 0.018 0.6829 0.5347 0.7077 1.0465 0.3165
T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 0.06 0.9553
TroC Satterthwaite Unequal 15.3 0.06 0.9554
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 2.47 0.1943
Comparison in Troponin C for Endoaden and Aortic 295
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Aortic 10 0.0721 0.2331 0 .3941 0 .1548 0 .2251 0 .4109 0 .0712
TroC Endoaden 10 0.5658 0.9502 1 .3346 0 .3696 0 .5373 0 .9809 0 .1699
TroC Diff (1-2) -1.104 -0.717 -0.33 0 .3113 0 .4119 0 .6092 0 .1842 T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 -3 89 0 0011 TroC Satterthwaite Unequal 12.1 -3.89 0 0021
Equality of Variances
Variable Method Nura DF Den DP F Value Pr > F
TroC Folded F 9 9 S.70 0.0162
Comparison in Troponin C for Endoaden and Parkmso 29S
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Endoaden 10 0. 5658 0. 9502 1.3346 0.3S96 0 5373 0.9809 0.1699
TroC Parkmso 10 2. 3304 2 S47 2.7636 0.2082 0.3027 0 5527 0.0957
TroC Dlff (1-2) -2 007 -1 .597 -1.187 0.3295 0.43S1 0.6449 0.195
T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 -8.19 <.0001 TroC Satterthwaite Unequal 14.2 -8.19 <.0001
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
TroC Folded F 9 9 3.15 0.1025
Comparison m Troponin C for Prostate and Prostati 297
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Prostate 10 -0 048 0. 1119 0.2717 0.1536 0.2234 0.4078 0.0706
TroC Prostati 10 0 .441 0. 6432 0 8454 0 1944 0.2827 0.5161 0.0894
TroC Dlff (1-2) -0 .771 -0 531 -0 292 0.1925 0.2547 0.3767 0.1139
T-Tests
Variable Method Variances t Value Pr > |t|
TroC Pooled Equal 18 -4.66 0.0002 TroC Satterthwaite Unequal 17.1 -4.66 0 0002
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 1.60 0.4938
Comparison m Troponin C for Prostate and Arthriti 298
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Arthriti 10 0.3642 0 .9682 1. 5722 0 .5807 0 .8443 1.5414 0.267
TroC Prostate 10 -0.048 0 .1119 0. 2717 0 .1536 0 .2234 0.4078 0.0706
TroC Dlff (1-2) 0.2761 0 .8563 1. 4365 0 .4666 0 .6176 0.9133 0.2762 T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 3.10 0 .00S2
TroC Satterthwaite Unequal 10.3 3.10 0 .0109
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 14.29 0.0005
Comparison in Troponin C for Prostate and Aortic
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Aortic 10 0.0721 0 .2331 0.3941 0.1548 0.2251 0.4109 0.0712
TroC Prostate 10 -0.048 0 .1119 0.2717 0.1536 0.2234 0.4078 0.0706
TroC Diff (1-2) -0.089 0 .1212 0.3319 0.1694 0.2242 0.3316 0.1003
T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 1.21 0.2424
TroC Satterthwaite Unequal 18 1.21 0.2424
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 1.02 0.9821
Comparison in Troponin C for Prostate and Parkinso 300
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Parkinso 10 2.3304 2 .547 2.7636 0.2082 0.3027 0.5527 0.0957
TroC Prostate 10 -0.048 0. 1119 0.2717 0.1536 0.2234 0.4078 0.0706
TroC Diff (1-2) 2.1852 2. 4351 2.685 0.201 0.266 0.3934 0.119
T-Tests
Variable Method Variances DF t Value Pr |t|
TroC Pooled Equal "* 18 20.47 <.0001 TroC Satterthwaite Unequal 16.6 20.47 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F TroC Folded F 9 9 1.84 0.3784
Comparison in Troponin C for Prostati and Arthriti 3
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev std Dev Std Err
TroC Arthriti 10 0.3642 0 .9682 1 .5722 0 .5807 0 .8443 1 .5414 0.267
TroC Prostati 10 0.441 0 .6432 0 .8454 0 .1944 0 .2827 0 .5161 0 .0894
TroC Diff (1-2) -0.267 0.325 0 .9165 0 .4757 0 .6296 0 .9311 0 .2816 T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 1.15 0 .2635 TroC Satterthwaite Unequal 11 1.15 0.2729
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 8.92 0.0032
Comparison in Troponin C for Prostati and Aortic 302
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Aortic 10 0.0721 0.2331 0.3941 0.1548 0.2251 0.4109 0.0712 TroC Prostati 10 0.441 0.6432 0.8454 0.1944 0.2827 0.5161 0.0894 TroC Diff (1-2) -0.65 -0.41 -0.17 0.1931 0.2555 0.3778 0.1143
T-Tests
Variable Method Variances t value Pr > |t|
TroC Pooled Equal 18 -3.59 0.0021 TroC Satterthwaite Unequal 17.1 -3.59 0.0022
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 1.58 0.5079
Comparison in Troponin C for Prostati and Parkinso 303
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Parkinso 10 2.3304 2.547 2.7S36 0. .2082 0.3027 0.5527 0.0957
TroC Prostati 10 0.441 0.6432 0.8454 0. .1944 0.2827 0.5161 0.0894
TroC Diff (1-2) 1.6286 1.9038 2.179 0. .2213 0.2929 0.4331 0.131
T-TeStS
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 14.54 <.0001
TroC Satterthwaite Unequal 17.9 14.54 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 1.15 0.8415
Comparison in Troponin C for Arthriti and Aortic 304
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Aortic 10 0.0721 0.2331 0.3941 0.1548 0.2251 0.4109 0.0712 TroC Arthriti 10 0.3642 0.9682 1.5722 0.5807 .0.8443 1.5414 0.267 TroC Diff (1-2) -1.316 -0.735 -0.155 0.4669 0.6179 0.9137 0.2763 T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 -2.66 0.0159
TroC Satterthwaite Unequal 10.3 -2.66 0.0234
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 14.07 0.0005
Comparison in Troponin C for Arthriti and Parkinso 305
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Arthriti 10 0.3642 0.9682 1.5722 0 .5807 0 .8443 1 .5414 0.267 TroC Parkinso 10 2.3304 2.547 2.7636 0 .2082 0 .3027 0 .5527 0.0957 TroC Diff (1-2) -2.175 -1.579 -0.983 0 .4792 0 .6342 0 .9379 0.2836
T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 -5.57 <.0001 TroC Satterthwaite Unequal 11.3 -5.57 0.0002
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
TroC Folded F 9 9 7.78 0.0054
Comparison in Troponin C for Aortic and Parkinso 306
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
TroC Aortic 10 0.0721 0. 2331 0.3941 0 .1548 0.2251 0.4109 0 .0712
TroC Parkinso 10 2.3304 2 .547 2.7636 0 .2082 0.3027 0.5527 0 .0957
TroC Diff (1-2) -2.565 -2 .314 -2.063 0 .2016 0.2667 0.3945 0 .1193
T-Tests
Variable Method Variances DF t Value Pr > |t|
TroC Pooled Equal 18 -19 .40 < .0001
TroC Satterthwaite Unequal 16.6 -19 .40 < .0001
Equality of Variances
Variable Method , Num DF Den DF F Value Pr > F TroC Folded F 9 9 1.81 0.3904 Comparison in Abeam Transglutaminase 2 for Cstitis and KldSton 307
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Cstitxs 10 0. 2326 0 .5033 0.774 0 .2603 0 .3785 0 .691 0.1197
AbT KidSton 10 -0 .018 0 .0466 0 .1115 0 .0624 0 .0907 0. 1655 0.0287
AbT Diff (1-2) 0. 1981 0 .4567 0 .7153 0 .2079 0 .2752 0 .407 0.1231 T-Tests
Variable Method Variances DF t Value Pr > M
AbT Pooled Equal 18 3.71 0 .0016 AbT Satterthwaite Unequal 10 3.71 0.0040
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AbT Folded F 9 9 17.43 0.0002
Comparison, in Abeam Transglutaminase 2 for Cstitis and Endoaden 308
The TTEST Procedure Statistics
Lower CB Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Cstitis 10 0.232S 0.5033 0.774 0.2603 0.3785 0.691 0.1197
AbT Endoaden 10 0.0S85 0.3355 0.6025 0.2568 0.3733 0.S815 0.118
AbT Diff (1-2) -0.185 0.1678 0.521 0.284 0.3759 0.5559 0.1681
T-Tests
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 1.00 0.3314 AbT Satterthwaite Unequal 18 1.00 0.3314
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AbT Folded F 9 9 1.03 0.9679
Comparison in Abeam Transglutaminase 2 for Cstitis and Prostate
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Cstitis 10 0.2326- 0 .5033 0.774 0.2603 0.3785 0.691 0.1197 AbT Prostate 10 0.0132 0.0745 0.1358 0.059 0.0857 0.1565 0.0271 AbT Diff (1-2) 0.171 0.4288 0.68S6 0.2073 0.2744 0.4058 0.1227
T-Tests
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 3.49 0.0026 AbT Satterthwaite Unequal 9.92 3.49 0.0059
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AbT Folded F 9 9 19.49 0.0001
Comparison in Abeam Transglutaminase 2 for Cstitis and Prostati 310
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Cstitis 10 0. 2326 0. 5033 0.774 0 .2603 0 .3785 0.691 0.1197
AbT Prostati 10 0. 0157 0. 5121 1 .0085 0 .4773 0 .6939 1.2668 0.2194
AbT Diff (1-2) -0 .534 -0 .009 0 .5163 0 .4223 0 .5589 0.8265 0.25 T-Tests
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 -0 04 0 9723
AbT Satterthwaite Unequal 13.9 -0 04 0. 9724
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F AbT Folded F 9 9 3 36 0.0854 Comparison in Abeam Transglutaminase 2 for Cstitis and Arthπti 311
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N N M Meeaann M Meeaann Mean Std Dev Std Dev Std Dev Std Err
AbT Arthrαti 1 100 11 . .77771144 2 2 . .55663355 3 3556 0 7616 1.1073 2 0214 0 .3501
AbT Cstitis 1 100 00 . .22332266 0 0 . .55003333 0 774 0 2603 0.3785 0 691 0 .1197
AbT Diff (1-2) 1 1 . .22882288 2 2 . .00660022 2.8376 0 6252 0.8274 1.2236 0.37
T-Tests
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 5.57 < 0001
AbT Satterthwaite Unequal 11.1 5.57 0 0002
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F AbT Folded F 9 9 8 56 0.0038 Comparison m Abeam Transglutaminase 2 for Cstitis and Aortic 312
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Aortic 10 -0 155 3.8143 7.7834 3.8164 5 5484 10 129 1 7545
AbT Cstitis 10 0.2326 0.5033 0.774 0 2603 0.3785 0.691 0.1197
AbT Diff (1-2) -0.384 3.311 7.0057 2 9714 3.9324 5.8153 1 7586
T-Tests
Variable Method Variances DF t Value Pr > ItI
AbT Pooled Equal 18 1.88 0 0760
AbT Satterthwaite Unequal 9.08 1.88 0 .0921
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AbT Folded F 9 9 214.91 <.0001
Comparison in Abeam Transglutaminase 2 for Cstitis and Parkinso 313
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Cstitis 10 0. 2326 0. 5033 0 .774 0.2603 0.3785 0.691 0.1197
AbT Parkinso 10 2. 7719 3. 0739 3. 3759 0.2904 0.4222 0.7708 0.1335
AbT Diff (1-2) -2 .947 -2 .571 -2 .194 0.303 0.4009 0.5929 0.1793 T-Tests
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 -14.34 <.0001
AbT Satterthwaite Unequal 17.8 -14.34 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AbT Folded F 9 9 1.24 0.7499
Comparison in Abeam Transglutaminase 2 for Kidston and Endoaden
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Endoaden 10 0. 0S85 0 .3355 0.6025 0.2568 0.3733 0.6815 0.118
AbT KidSton 10 -0 .018 0 .0466 0.1115 0.0624 0.0907 0.1655 0.0287
AbT Diff (1-2) 0. 0337 0 .2889 0.5441 0.2052 0.2716 0.4017 0.1215
T-Tests
Variable Method Variances t Value Pr > ] t |
AbT Pooled Ec[UaI 18 2.38 0.0287 AbT Satterthwaite Unequal 10.1 2.38 0.0386
Equality of Variances
Variable Method Num DF Den DF P Value Pr > F
AbT Folded F 9 9 16.95 0.0003
Comparison in Abeam Transglutaminase 2 for KidSton and Prostate 315
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT KidSton 10 -0 .018 0. 0466 0. 1115 0. 0624 0. 0907 0 .1655 0 .0287 AbT Prostate 10 0.0132 0. 0745 0. 1358 0 .059 0. 0857 0 .1565 0 .0271 AbT Diff (1-2) -0 .111 -0 .028 0 .055 0. 0667 0. 0882 0 .1305 0 .0395
T-Tests
Variable Method Variances DF t Value Pr > ItI
AbT Pooled Equal 18 -0 .71 0 .4886 AbT Satterthwaite Unequal 17.9 -0 .71 0 .4886
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AbT Folded F 9 9 1.12 0.8702
Comparison in Abeam Transglutaminase 2 for KidSton and Prostati 316
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT KidSton 10 -0.018 0. 0466 0.1115 0 .0624 0 .0907 0.1655 0.0287
AbT Prostati 10 0.0157 0. 5121 1.0085 0 .4773 0 .6939 1.2668 0.2194
AbT Diff (1-2) -0.93 -0 .466 -57E-5 0 .3739 0 .4948 0.7318 0.2213 T-Tests
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 -2.10 0.0498 AbT Satterthwaite Unequal 9.31 -2.10 0.0637
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AbT Folded F 9 9 58.58 <.0001
Comparison in Abeam Transglutaminase 2 for KidSton and Arthriti 317
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Arthriti 10 1. 7714 2 .5635 3.355S 0.7616 1.1073 2.0214 0.3501
AbT KidSton 10 -0 .018 0 .046S 0.1115 0.0624 0.0907 0.1655 0.0287
AbT Diff (1-2) 1. 7788 2 .5169 3.255 0.5936 0.785S 1.1617 0.3513
T-Tests
Variable Method Variances DF t Value Pr > ]t|
AbT Pooled Equal 18 7.16 c.0001 AbT Satterthwaite Unequal 9.12 7.16 .= .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F AbT Folded F 9 9 149.15 <.0001 Comparison in Abeam Transglutaminase 2 for KidSton and Aortic 318
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Aortic 10 -0 .155 3 .8143 7.7834 3.8164 5.5484 10.129 1.7545
AbT KidSton 10 -0 .018 0 .0466 0.1115 0.0624 0.0907 0.1655 0.0287
AbT Diff (1-2) 0 .081 3 .7677 7.4544 2.9649 3.9238 5.8026 1.7548
T-Tests
Variable Method Variances t Value Pr > |t|
AbT Pooled Equal 18 2.15 0.0457 AbT Satterthwaite Unequal 9 2.15 0.0603
Equality of Variances
Variable Method Num DF Den DF P Value Pr > F
AbT Folded F 9 9 3744.92 <.0001
Comparison in Abeam Transglutaminase 2 for KidSton and Parkinso 319
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Std Dev Std Dev Std Dev Std Err
AbT KidSton 10 -0.018 0.0466 0 .1115 0 .0624 0 .0907 0 .1655 0 .0287 AbT Parkinso 10 2.7719 3.0739 3 .3759 0 .2904 0 .4222 0 .7708 0 .1335 AbT Diff (1-2) -3.314 -3.027 -2.74 0 .2307 0 .3054 0 .4516 0 .1366 T-Tests
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 -22 17 ■c.OOOl
AbT Satterthwaite Unequal 9.83 -22.17 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AbT Folded F 9 9 21.69 <.0001
Comparison in Abeam Transglutaminase 2 for Endoaden and Prostate 320
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Endoaden 10 0.0685 0.335S 0.6025 0.2568 0.3733 0.6815 0.118 AbT Prostate 10 0.0132 0.074S 0.1358 0.059 0.0857 0.1565 0.0271 AbT Diff (1-2) 0.006S 0.261 0.5155 0.2046 0.2708 0.4005 0.1211
T-Tests
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 2 .15 0.0450 AbT Satterthwaite Unequal 9.95 2 .15 0.0567
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AbT Folded F 9 9 18.96 0.0002
Comparison in Abeam Transglutaminase 2 for Endoaden and Prostati
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Endoaden 10 0.0685 0 .3355 0. 6025 0 .2568 0.3733 0.6815 0.118
AbT Prostati 10 0.0157 0 .5121 1. 0085 0 .4773 0.6939 1.2668 0 .2194
AbT Diff (1-2) -0.7 - 0.177 0. 3469 0.421 0.5572 0.8239 0 .2492
T-Tests
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 -0 .71 0 .4876 AbT Satterthwaite unequal 13.8 -0 .71 0 .4903
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AbT Folded F 9 9 3.46 0.0789
Comparison in Abeam Transglutaminase 2 for Endoaden and Arthriti 322
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Arthriti 10 1 .7714 2 .5635 3 .3556 0 .7616 1 .1073 2.0214 0.3501
AbT Endoaden 10 0 .0685 0 .3355 0 .6025 0 .2568 0 .3733 0.6815 0.118
AbT Diff (1-2) 1 .4517 2.228 3 .0043 0 .6243 0 .8262 1.2219 0.3695 T-Tests
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 6 03 < 0001
AbT Satterthwaite Unequal 11 6.03 <.0001
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F AbT Folded F 9 9 8.80 0.0034 Comparison in Abeam Transglutaminase 2 for Endoaden and Aortic 323
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Aortic 10 -0.1S5 3 .8143 7.7834 3.8164 5.5484 10.129 1.7545
AbT Endoaden 10 0.0685 0 .3355 0.6025 0.2568 0.3733 0.6815 0.118
AbT Diff (1-2) -0.216 3 .4788 7.1733 2.9712 3.9321 5.815 1.7585
T-Tests
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 1.98 0.0634 AbT Satterthwaite Unequal 9.08 1.98 0.0790
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AbT Folded F 9 9 220.92 <.0001
Comparison in Abeam Transglutaminase 2 for Endoaden and Parkmso 324
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Endoaden 10 0. 0685 0. 3355 0.6025 0.2568 0.3733 0.6815 0.118
AbT Parkmso 10 2. 7719 3. 0739 3.3759 0.2904 0.4222 0.7708 0.1335
AbT Diff (1-2) —3 .113 -2 .738 -2.364 0.3011 0.3985 0.5893 0.1782
T-Tests
Variable Method Variances t Value Pr > |t|
AbT Pooled Equal 18 -15.37 <.0001 AbT Satterthwaite Unequal 17.7 -15.37 <.0001
Equality of Variances
Variable Method Num DF Den DF P Value Pr > F
AbT Folded F 9 9 1.28 0.7196
Comparison in Abeam Transglutaminase 2 for Prostate and Prostati 325
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Prostate 10 0. 0132 0. 0745 0 .1358 0.059 0 .0857 0.1565 0 .0271
AbT Prostati 10 0. 0157 0. 5121 1 .0085 0 .4773 0 .6939 1.2668 0 .2194
AbT Diff (1-2) -0 .902 -0 .438 0 .0269 0 .3736 0 .4944 0.7311 0 .2211 T-Tests
Variable Method Variances DF t Value Pr > It=I
AbT Pooled Equal 18 -1.98 0 .0633
AbT Satterthwaite Unequal 9.27 -1.98 0 .0782
Equality of Variances
Variable Method Nura DP Den DP F Value Pr > F
AbT Folded F 9 9 65.52 <.0001
Comparison in Abeam Transglutaminase 2 for Prostate and Arthriti 326
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Arthriti 10 1. .7714 2 .5635 3.3556 0 .7616 1.1073 2 .0214 0 .3501
AbT Prostate 10 0. .0132 0 .0745 0.1358 0.059 0.0857 0 .1565 0 .0271
AbT Diff (1-2) 1. .7512 2.489 3.2268 0 .5934 0.7853 1 .1613 0 .3512
T-Tests
Variable Method Variances DF t Value Pr >
Figure imgf000497_0001
AbT Pooled Equal 18 7.09 < .0001
AbT Satterthwaite Unequal 9 .11 7.09 < .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F AbT Folded F 9 9 166.83 <.0001 Comparison in Abeam Transglutaminase 2 for Prostate and Aortic 327
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Aortic 10 -0.155 3 .8143 7.7834 3.8164 5.5484 10.129 1.7545
AbT Prostate 10 0.0132 0 .0745 0.1358 0.059 0.0857 0.1565 0.0271
AbT Diff (1-2) 0.0532 3 .7398 7.4264 2.9648 3.9237 5.8025 1.7548
T-TeStS
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 2.13 0.0471
AbT Satterthwaite Unequal 9 2.13 0.0619
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AbT Folded F 9 9 4188.81 <.0001
Comparison in Abeam Transglutaminase 2 for Prostate and Parkinso 328
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Parkinso 10 2.7719 3.0739 3 .3759 0 .2904 0 .4222 0 .7708 0 .1335 AbT Prostate 10 0.0132 0.0745 0 .1358 0.059 0 .0857 0 .1565 0 .0271 AbT Diff (1-2) 2.7132 2. 9994 3 .2856 0 .2302 0 .3046 0 .4505 0 .1362 T-Tests
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 22.02 <.0001 AbT Satterthwaite Unequal 9.74 22.02 <.0001
Equality of Variances
Variable Method Nutn DF Den DF F Value Pr > F
AbT Folded F 9 9 24.25 <.0001
Comparison in Abeam Transglutaminase 2 for Prostati and Arthriti 329
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Arthriti 10 1 .7714 2 .5635 3.3556 0 .7616 1.1073 2.0214 0 .3501
AbT Prostati 10 0 .0157 0 .5121 1.0085 0 .4773 0.6939 1.2668 0 .2194
AbT Diff (1-2) 1 .1832 2 .0514 2.9196 0 .6982 0.924 1.3664 0 .4132
T-Tests
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 4.96 0 .0001
AbT Satterthwaite Unequal 15.1 4.96 0 .0002
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F AbT Folded F 9 9 2.55 0.1801
Comparison in Abeam Transglutaminase 2 for Prostati and Aortic 330
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Aortic 10 -0.155 3 .8143 7.7834 3.8164 5.5484 10.129 1.7545
AbT Prostati 10 0.0157 0 .5121 1.0085 0.4773 0.6939 1.2668 0.2194
AbT Diff (1-2) -0.413 3 .3022 7.0171 2.9876 3.9538 5.847 1.7682
T-Tests
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 1.87 0.0782 AbT Satterthwaite Unequal 9.28 1.87 0.0937
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AbT Folded F 9 9 63.93 <.0001
Comparison in Abeam Transglutaminase 2 for Prostati and Parkinso 331
The TTEST Procedure Statistics
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Parkinso 10 2 .7719 3 .0739 3 .3759 0.2904 0.4222 0. 7708 0.1335
AbT Prostati 10 0 .0157 0 .5121 1 .0085 0.4773 0.6939 1. 2668 0.2194
AbT Diff (1-2) 2 .0221 2 .5618 3 .1015 0.434 0.5744 0. 8494 0.2569 T-τests
Variable Method Variances DF t Value Pr > 11 J
AbT Pooled Equal 18 9.97 <.0001
AbT Satterthwaite Unequal 14.9 9.97 <=.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F AbT Folded F 9 9 2.70 0.1549 Comparison in Abeam Transglutaminase 2 for Arthriti and Aortic 332
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Aortic 10 -0 .155 3 .8143 7.7834 3.8164 5.5484 10.129 1.7545
AbT Arthriti 10 1. 7714 2 .5635 3.355S 0.7616 1.1073 2.0214 0.3501
AbT Diff (1-2) -2 .508 1 .2508 5.0096 3.0229 4.0006 5.9162 1.7891
T-Tests
Variable Method Variances DF t Value Pr > |t|
AbT Pooled Equal 18 0.70 0.4934 AbT Satterthwaite Unequal 9.72 0.70 0.5009
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AbT Folded F 9 9 25.11 <.0001
Comparison in Abeam Transglutaminase 2 for Arthriti and Parkinso 333
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Arthriti 10 1. 7714 2 .5635 3.3556 0.7616 1.1073 2.0214 0.3501
AbT Parkinso 10 2. 7719 3 .0739 3.3759 0.2904 0.4222 0.7708 0.1335
AbT Diff (1-2) -1 .298 -0.51 0.2769 0.6332 0.8379 1.2392 0.3747
T-Tests
Variable Method Variances t Value Pr > |t|
AbT Pooled Equal 18 -1.36 0.1900 AbT Satterthwaite Unequal 11.6 -1.36 0.1991
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F AbT Folded F 9 9 6.88 0.0084 Comparison in Abeam Transglutaminase 2 for Aortic and Parkinso 334
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
AbT Aortic 10 -0.155 3.8143 7.7834 3.8164 5.5484 10.129 1.7545 AbT Parkinso 10 2.7719 3.0739 3.3759 0.2904 0.4222 0.7708 0.1335 AbT Diff (1-2) -2.956 0.7404 4.4372 2.9731 3.9346 5.8186 1.7596 T-Tests
Variable Method Variances DF t Value Pr > ItI
AbT Pooled Equal 18 0.42 0 .6789
AbT Satterthwaite Unequal 9.1 0.42 0 .5837
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
AbT Folded F 9 9 172.68 <.0001
Comparison in PGRP-I Beeta for Cstitis and KidSton 335
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Cstitis 10 102.25 190.7 279 .14 85 .043 123 .64 225. 39.098
PGRP KidSton 10 47.433 55.486 63. 539 7. 7434 11. 258 20.5 3.56
PGRP Diff (1-2) 52.728 135.21 217 .69 66 .333 87. 787 129. 39.26
T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 3.44 0 .0029
PGRP Satterthwaite Unequal 9 .15 3.44 0 .0072
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 120.62 <.0001
Comparison in PGRP-I Beeta for Cstitis and Endoaden 336
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Cstitis 10 102.25 190.7 279.14 85.043 123.64 225.72 39.098 PGRP Endoaden 10 319.45 512.2 704.94 185.33 269.44 491.89 85.203 PGRP Diff (1-2) -518.5 -321.5 -124.5 158.39 209.62 309.99 93.746
T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 -3.43 0.0030 PGRP Satterthwaite Unequal 12.6 -3.43 0.0047
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 4.75 0.0297
Comparison in PGRP-I Beeta for Cstitis and Prostate 337
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Cstitis 10 102.25 190.7 279.14 85.043 123.64 225.72 39.098
PGRP Prostate 10 -0.141 1.0337 2.2086 1.1297 1.6424 2.9985 0.5194
PGRP Diff (1-2) 107.51 189.66 271.81 66.066 87.433 129.3 39.101 T-Tests
Variable Method Variances DP t Value Pr > |t|
PGRP Pooled Equal 18 4.85 0.0001 PGRP Satterthwaite Unequal 9 4.85 0.0009
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 5666.64 <.0001
Comparison in PGRP-I Beeta for Cstitis and Prostati 338
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Cstitis 10 102.25 190.7 279 .14 85. 043 123 .64 225.72 39. 098
PGRP Prostati 10 195.76 387.17 578 .58 184 .05 267 .57 488.48 84. 614
PGRP Diff (1-2) -392.3 -196.5 -0. 642 157 .49 208 .42 308.22 93 .21
T-Tests
Variable Method Variances DF t Value Pr > It|
PGRP Pooled Equal 18 -2.11 0 .0493
PGRP Satterthwaite Unequal 12.7 -2.11 0 .0556
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 4.68 0.0310
Comparison in PGRP-I Beeta for Cstitis and Arthriti 339
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Arthriti 10 270.61 449.04 627 .46 171 .56 249 .42 455.34 78. 873
PGRP Cstitis 10 102.25 190.7 279. .14 85. 043 123. .64 225.72 39. 098
PGRP Diff (1-2) 73.393 258.34 443. .29 148 .74 196. .85 291.1 88. 032
T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 2.93 0.0089
PGRP Satterthwaite Unequal 13 .2 2.93 0.0115
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 4.07 0.0484
Comparison in PGRP-I Beeta for Cstitis and Aortic
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Aortic 10 169.14 308.2 447 .26 133 .71 194. 39 354 .89 61.473
PGRP Cstitis 10 102.25 190.7 279 .14 85. 043 123. 64 225 .72 39.098
PGRP Diff (1-2) -35.55 117.51 270 .56 123 .09 162 .9 240 .91 72.853 T-Tests
Variable Method Variances DF t Value Pr > It]
PGRP Pooled Equal 18 1.61 0 .1242 PGRP Satterthwaite Unequal IS.3 1.Sl 0.1273
Equality of Variances
Variable Method Num DF Den DP F Value Pr > F
PGRP Folded F 9 9 2.47 0.1938
Comparison in PGRP-I Beeta for Cstitis and Parkmso 341
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean std Dev Std Dev Std Dev Std Err
PGRP Ostitis 10 102.25 190.7 279.14 85.043 123.54 225.72 39.098
PGRP Parkmso 10 79.041 83.549 88.057 4.3348 S.302 11.505 1.9929
PGRP Diff (1-2) 24.898 107.15 189.39 6S.145 87.539 129.45 39.149
T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 2.74 0.0135 PGRP Satterthwaite Unequal 9.05 2.74 0.0229
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 384.90 <.0001
Comparison in PGRP-I Beeta for Kidston and Endoaden 342
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Endoaden 10 319 .45 512.2 704.94 185.33 269.44 491.89 85.203
PGRP KidSton 10 47. 433 55.486 63.539 7.7434 11.258 20.552 3.56
PGRP Diff (1-2) 277 .55 456.71 635.87 144.09 190.69 281.99 85.278
T-Tests
Variable Method Variances DF t Value Pr >
PGRP Pooled Equal 18 5.36 <.oooi PGRP Satterthwaite Unequal 9.03 5.36 0.0005
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 572.82 <.0001
Comparison in PGRP-I Beeta for Kidston and Prostate 343
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP KidSton 10 47 .433 55.486 63 .539 7 .7434 11.258 20.552 3.56
PGRP Prostate 10 -0 .141 1.0337 2. 2086 1 .1297 1.6424 2.9985 0.5194
PGRP Diff (1-2) 46 .894 54.452 62 .011 6 .0786 8.0447 11.897 3.5977 T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 15.14 <.0001
PGRP Satterthwaite unequal 9.38 15.14 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 46 98 <.0001
Comparison in PGRP-I Beeta for KidSton and Prostati 344
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP KidSton 10 47.433 55.486 63.539 7.7434 11.258 20.552 3.56 PGRP Prostati 10 195.76 387.17 578.58 184.05 267.57 488.48 84.614 PGRP Diff (1-2) -509.6 -331.7 -153.8 143.09 189.37 280.04 84.689
T-Tests
Variable Method Variances t Value Pr >
PGRP Pooled Equal 18 -3.92 0.0010 PGRP Satterthwaite Unequal 9.03 -3.92 0.0035
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 564.92 <.0001
Comparison m PGRP-I Beeta for KidSton and Arthπti 345
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Arthnti 10 270 .61 449 .04 627 .46 171.56 249.42 455.34 78.873
PGRP KidSton 10 47. 433 55. 486 63 .539 7.7434 11.258 20.552 3.56
PGRP Diff (1-2) 227 .68 393 .55 559.43 133.4 176.55 261.08 78.954
T-Tests
Variable Method Variances t Value Pr > |t|
PGRP Pooled Equal 18 4.98 <.0001 PGRP Satterthwaite Unequal 9.04 4.98 0.0007
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 490.86 <.0001
Comparison in PGRP-I Beeta for KidSton and Aortic 346
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Aortic 10 169. .14 308.2 447 .26 133.71 194 .39 354 .89 61 .473
PGRP KidSton 10 47.433 55.486 63. 539 7.7434 11. 258 20. 552 3.56
PGRP Diff (1-2) 123, .35 252.72 382 .08 104.04 137 .69 203 .62 61 .576 T-Tests
Variable Method Variances DF t Value Pr > ItI
PGRP Pooled Equal 18 4.10 0 0007
PGRP Satterthwaite Unequal 9.06 4.10 0 .002S
Equality of Variances
Variable Method Num DF Den DP F Value Pr > F
PGRP Folded F 9 9 298.17 <.0001
Comparison in PGRP-I Beeta for KidSton and Parkmso 347
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Ston 10 47. .433 55. 486 63. 539 7 .7434 11 .258 20.552 3.56 PGRP kmso 10 79. .041 83. 549 88. 057 4 .3348 6 .302 11.505 1 .9929 PGRP f (1-2) -35.63 -28 .06 -19 .49 6 .8933 9. 1228 13.491 4 .0798
T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 -6.88 < .0001
PGRP Satterthwaite Unequal 14.1 -6.88 < .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 3.19 0.0989
Comparison m PGRP-I Beeta for Endoaden and Prostate 348
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Endoaden 10 319.45 512.2 704.94 185.33 269.44 491.89 85.203
PGRP Prostate 10 -0.141 1.0337 2.2086 1.1297 1.6424 2.9985 0.5194
PGRP Diff (1-2) 332.15 511.16 690.17 143.96 190.52 281.75 85.205
T-Tests
Variable Method Variances t Value Pr > |t|
PGRP Pooled Equal 18 6.00 <-0001 PGRP Satterthwaite Unequal 9 6.00 0.0002
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 26911.4 <.0001
Comparison m PGRP-I Beeta for Endoaden and Prostati 349
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Endoaden 10 319.45 512.2 704 .94 185 .33 269 .44 491 .89 85. 203 PGRP Prostati 10 195.76 387.17 578 .58 184 .05 267 .57 488 .48 84. 614 PGRP Diff (1-2) -127.2 125.03 377 .31 202 .89 268 .51 397 .07 120 .08 T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 1.04 0.3116
PGRP Satterthwaite Unequal 18 1.04 0.3116
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 1.01 0.9838
Comparison in PGRP-I Beeta for Endoaden and Arthriti 350
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Arthriti 10 270. 61 449. 04 627.46 171.56 249.42 455.34 78.873
PGRP Endoaden 10 319. 45 512 .2 704.94 185.33 269.44 491.89 85.203
PGRP Diff (1-2) -307 .1 -63. IS 180.77 196.17 259.62 383.93 116.11
T-Tests
Variable Method Variances t Value Pr > |t|
PGRP Pooled Equal 18 -0.54 0.5931 PGRP Satterthwaite Unequal 17.9 -0.54 0.5932
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 1.17 0.8219
Comparison in PGRP-I Beeta for Endoaden and Aortic 351
The TTEST Procedure Statistics
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Aortic IQ 169.14 308.2 447.26 133 .71 194 .39 354.89 61. 473
PGRP Endoaden 10 319.45 512.2 704.94 185. .33 269 .44 491.89 85. 203
PGRP Diff (1-2) -424.7 -204 16.738 177. .52 234 .93 347.42 105 .06
T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 -1.94 0.0680
PGRP Satterthwaite Unequal 16.4 -1.94 0.0696
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 1.92 0.3449
Comparison in PGRP-I Beeta for Endoaden and Parkinso
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Endoaden 10 319.45 512.2 704.94 185.33 269.44 491.89 85.203
PGRP Parkinso 10 79.041 83.549 88.057 4.3348 6.302 11.505 1.9929
PGRP Diff (1-2) 249.59 428.65 607.7 144 190.57 281.82 85.227 T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 5.03 <.0001
PGRP Satterthwaite Unequal 9.01 5.03 0 0007
Equality of Variances
Variable Method Nura DF Den DP F Value Pr > F
PGRP Folded F 9 9 1827.91 <.0001
Comparison in PGRP-I Beeta for Prostate and Prostati 353
The TTEST Procedure Statistics
Variable Disease N Mean Mean Mean Stα Dev Std Dev Std Dev Std Err
PGRP Prostate 10 -0.141 1.0337 2.2086 1.1297 1.6424 2.9985 0. 5194
PGRP Prostati 10 195.76 387.17 578.58 184.05 267.57 488.48 84 .614
PGRP Diff (1-2) -563.9 -38S.1 -208.4 142.97 189.21 279.8 84 .615
T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 -4.56 0.0002
PGRP Satterthwaite Unequal 9 -4.56 0.0014
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 26540.1 <-0001
Comparison in PGRP-I Beeta for Prostate and Arthriti 354
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL upper CL
Variable Disease K Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Arthriti 10 270.61 449.04 627.46 171. .56 249. .42 455.34 78 .873
PGRP Prostate 10 -0.141 1.0337 2.2086 1.1297 1.6424 2.9985 0.5194
PGRP Diff (1-2) 282.29 448 613.71 133 .27 176, .37 260.82 78 .875
T-TestS
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 5.68 <.0001
PGRP Satterthwaite Unequal 9 5.68 0.0003
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
PGRP Folded F 9 9 23061.1 <.0001
Comparison in PGRP-I Beeta for Prostate and Aortic 355
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Aortic 10 169 .14 308.2 447.26 133.71 194.39 354.89 61.473
PGRP Prostate 10 -0. 141 1.0337 2.2086 1.1297 1.6424 2.9985 0.5194
PGRP Diff (1-2) 178 .01 307.17 436.32 103.87 137.46 203.28 61.475 T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 5.00 <.0001
PGRP Satterthwaite Unequal 9 5.00 0.0007
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 1400B.3 <.0001
Comparison in PGRP-I Beeta for Prostate and Parkmso 356
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease K Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Parkmso 10 79.041 83 .549 88. .057 4 .3348 6.302 11.505 1 .9929
PGRP Prostate 10 -0.141 1. 0337 2.2086 1 .1297 1.6424 2.9985 0 .5194
PGRP Dlff (1-2) 78.189 82 .516 86 .842 3 .4796 4.6051 6.8101 2 .0594
T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 40.07 < :.0001
PGRP Satterthwaite Unequal 10.2 40.07 < :.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 14.72 0.0005
Comparison in PGRP-I Beeta for Prostati and Arthriti
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP hπti 10 270.61 449.04 627 .46 171 .56 249 .42 455. 34 78. 873 PGRP statl 10 195.76 387.17 578 .58 184 .05 267 .57 488. 48 84. 614 PGRP f (1-2) -181.2 61.872 304 .89 195 .44 258 .66 382. 51 115 .67
T-Tests
Variable Method Variances DF t Value Pr > ItI
PGRP Pooled Equal 18 0.53 0 .5993
PGRP Satterthwaite Unequal 17.9 0.53 0 .5993
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 1.15 0.8376
Comparison m PGRP-I Beeta for Prostati and Aortic 358
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Aortic 10 169.14 308.2 447.26 133.71 194.39 354.89 61.473
PGRP Prostati 10 195.76 387.17 578.58 184.05 267.57 488.48 84.614
PGRP Diff (1-2) -298.7 -78.96 140.76 176.71 233.86 345.84 104.59 T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 -0.76 0 .4600
PGRP Satterthwaite Unequal 16.4 -0.76 0 .4609
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 1.89 0.35S1
Comparison in PGRP-I Beeta for Prostati and Parkinso 359
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Parkinso 10 79.041 83.549 88.057 4.3348 6.302 11.505 1.9929
PGRP Prostati 10 195.76 387.17 578.58 184.05 267.57 488.48 84.614
PGRP Diff (1-2) -481.4 -303.6 -125.8 143 189.25 279.87 84.637
T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 -3.59 0.0021 PGRP Satterthwaite Unequal 9.01 -3.59 0.0059
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 1802.70 <.0001
Comparison in PGRP-I Beeta for Arthriti and Aortic 360
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Aortic 10 169. 14 308 .2 447.26 133.71 194.39 354.89 61.473
PGRP Arthriti 10 270. 61 449. 04 627.46 171.56 249.42 455.34 78.873
PGRP Diff (1-2) -350 .9 -140 .8 69.255 168.96 223.61 330.67 99.999
T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 -1.41 0.1761 PGRP Satterthwaite Unequal 17 -1.41 0.1771
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PGRP Folded F 9 9 1.65 0.4692
Comparison in PGRP-I Beeta for Arthriti and Parkinso 361
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PGRP Arthriti 10 270 .61 449 .04 627 .46 171.56 249.42 455.34 78.873
PGRP Parkinso 10 79. 041 83. 549 88. 057 4.3348 6.302 11.505 1.9929
PGRP Diff (1-2) 199 .73 365 .49 531 .25 133.31 176.42 260.9 78.898 T-Tests
Variable Method Variances DF t Value Pr > |t|
PGRP Pooled Equal 18 4.63 0 0002 PGRP Satterthwaite Unequal 9 01 4.63 0 0012
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
PGRP Folded F 9 9 1566.39 <.0001
Comparison in PGRP-I Beeta for Aortic and Parkmso 362
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev std Dev Std Dev Std Err
PGRP Aortic 10 169 .14 308.2 447.26 133 .71 194 .39 354.89 61.473 PGRP Parkmso 10 79. 041 83.549 88.057 4.3348 6. 302 11.505 1.9929 PGRP Diff (1-2) 95. 435 224.65 353.87 103 .92 137 .53 203.38 61.505
T-Tests
Variable Method Variances DF t Value Pr > ]t|
PGRP Pooled Equal 18 3.65 0.0018 PGRP Satterthwaite Unequal 9.02 3.65 0.0053
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
PGRP Folded F 9 9 951.49 <.0001
Comparison in PSA for Cstitis and KidSton 363
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Cstitis 10 15.23 24.02 32.809 8.4515 12 .287 22.432 3.8855 PSA KidSton 10 3.9651 4.3355 4.7059 0.3561 0.5178 0.9452 0.1637 PSA Diff (1-2) 11.514 19.684 27.854 6.5708 8.696 12.86 3.889
T-Tests
Variable Method Variances DF t Value Pr > |t|
PSA Pooled Equal 18 5.06 <:.0001 PSA Satterthwaite Unequal 9.03 5.06 0.0007
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
PSA Folded F 9 9 563.19 <.0001
Comparison in PSA for Cstitis and Endoaden 364
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Cstitis 10 15.23 24.02 32.809 8. 4515 12.287 22 .432 3 .8855 PSA Endoaden 10 21.459 34.504 47.55 12 .543 18.236 33 .292 5 .7667 PSA Diff (1-2) -25.09 -10.48 4.1241 11 .749 15.549 22 .994 6 .9536 T-Tests
Variable Method Variances DF t Value Pr > |t|
PSA Pooled E Eqquuaall 18 -1 .Sl 0 .1489 PSA Satterthwaite Unequal 15.8 -1 .51 0 .1514
Equality of Variances
Variable Method Num DF Den DF F Value Pr > P
PSA Folded F 9 9 2.20 0.2551
Comparison in PSA for Ostitis and Prostate 3S5
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Ostitis 10 15.23 24.02 32.809 8.4515 12.287 22.432 3.8855
PSA Prostate 10 0.1072 0.2542 0.4012 0.1414 0.2055 0.3752 0.065
PSA Diff (1-2) 15.601 23.765 31.93 6.5659 8.6895 12.85 3.8861
T-Tests
Variable Method Variances DF t Value Pr > |t|
PSA Pooled Equal 18 6.12 <.0001 PSA Satterthwaite Unequal 9.01 6.12 0.0002
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PSA Folded F 9 9 3573.87 <.0001
Comparison in PSA for Ostitis and Prostati 366
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Ostitis 10 15.23 24.02 32 .809 8.4515 12 .287 22.432 3. 8855 PSA Prostati 10 38.016 40.419 42.823 2.3108 3.3595 6.1332 1.0624 PSA Diff (1-2) -24.86 -16.4 -7.937 6.806 9.0072 13.32 4.0282
T-Tests
Variable Method Variances DF t Value Pr > |t|
PSA Pooled Equal 18 -4.07 0.0007 PSA Satterthwaite Unequal 10.3 -4.07 0.0021
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PSA Folded F 9 9 13.38 0.0007
Comparison in PSA for Cstitis and Arthriti 367
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Arthriti 10 13.286 24.616 35 .946 10.894 15 .838 28.915 5.0085
PSA Cstitis 10 15.23 24.02 32 .809 8.4515 12 .287 22.432 3.8855
PSA Diff (1-2) -12.72 0.5963 13 .914 10.71 14 .174 20.961 6.339 T-Tests
Variable > Method Variances DF t Value Pr > |t|
PSA Pooled Equal 18 0.09 0.92S1 PSA Satterthwaite Unequal 17 0.09 0.92S2
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
PSA Folded F 9 9 1.66 0.4611
Comparison in PSA for Ostitis and Aortic 368
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Aortic 10 35.877 41. .647 47 .417 5 .5479 8. 0657 14.725 2 .5506
PSA Ostitis 10 15.23 24.02 32 .809 8 .4515 12 .287 22.432 3 .8855
PSA Diff (1-2) 7.8629 17. .628 27 .393 7 .8531 10 .393 15.369 4 .6479
T-Tests
Variable Method Variances DF t Value Pr > |t|
PSA Pooled Equal 18 3.79 0 .0013
PSA Satterthwaite Unequal 15.5 3.79 0 .0017
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
PSA Folded F 9 9 2.32 0.2258
Comparison in PSA for Ostitis and Parkinso 369
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Cstitis 10 15.23 24 .02 32.809 8.4515 12.287 22.432 3.8855
PSA Parkinso 10 11.998 12. 412 12.827 0.3985 0.5793 1.0576 0.1832
PSA Diff (1-2) 3.4351 11. 607 19.78 6.5723 8.698 12.863 3.8898
T-Tests
Variable Method Variances t Value Pr > |t|
PSA Pooled Equal 18 2.98 0.0080 PSA Satterthwaite Unequal 9.04 2.98 0.0153
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PSA Folded F 9 9 449.84 <.0001
Comparison in PSA for KidSton and Endoaden 370
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Endoaden 10 21.459 34.504 47.55 12 .543 18 .236 33.292 5 .7667
PSA KidSton 10 3.9651 4.3355 4.7059 0. 3561 0. 5178 0.9452 0 .1637
PSA Diff (1-2) 18.049 30.169 42.289 9. 7474 12.9 19.077 5.769 T-Tests
Variable Method Variances DF t Value Pr > |t|
PSA Pooled Equal 18 5.23 <.0001 PSA Satterthwaite Unequal 9.01 5.23 0.0005
Equality of Variances
Variable Method Nura DP Den DF F Value Pr > F
PSA Folded F 9 9 1240.55 c.OOOl
Comparison in PSA for KidSton and Prostate 371
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA KidSton 10 3. .9651 4.3355 4.7059 0.3561 0.5178 0.9452 0.1637 PSA Prostate 10 0. .1072 0.2542 0.4012 0.1414 0.2055 0.3752 0.065 PSA Diff (1-2) 3. .7112 4.0813 4.4514 0.2976 0.3939 0.5825 0.1762
T-Tests
Variable Method Variances DF t Value Pr > |t|
PSA Pooled Equal 18 23.17 <.0001 PSA Satterthwaite Unequal 11.8 23.17 <.0001
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
PSA Folded F 9 9 6.35 0.0111
Comparison in PSA for KidSton and Prostati 372
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA KidSton 10 3.9651 4.3355 4.7059 0 .3561 0.5178 0.9452 0.1637 PSA Prostati 10 38.016 40.419 42.823 2.3108 3.3595 6.1332 1.0624 PSA Diff (1-2) -38.34 -36.08 -33.83 1.8162 2.4036 3.5545 1.0749
T-Tests
Variable Method Variances DF t Value Pr > |t|
PSA Pooled Equal 18 -33. .57 <.0001 PSA Satterthwaite Unequal 9.43 -33..57 <.0001
Equality of Variances
Variable Method Hum DF Den DP F Value Pr > F
PSA Folded F 9 9 42.10 <:.0001
Comparison in PSA for KidSton and Arthriti 373
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Arthriti 10 13 .286 24.616 35 .946 10 .894 15.838 28.915 5.0085
PSA KidSton 10 3. 9651 4.3355 4. 7059 0. 3561 0.5178 0.9452 0.1637
PSA Diff (1-2) 9. 7522 20.28 30 .808 8. 4669 11.205 16.571 5.0112 T-Tests
Variable Method Variances DF t Value Pr > |t|
PSA Pooled Equal 18 4.05 0 .0008
PSA Satterthwaite U Unneeqσuuaall 9.02 4.05 0 .0029
Equality of Variances
Variable Method Num DF Den DF P Value Pr > F
PSA Folded F 9 9 935.78 <.0001
Comparison in PSA for KidSton and Aortic 374
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Aortic 10 35 .877 41.547 47 .417 5 .5479 8 .0657 14.725 2.5506 PSA KidSton 10 3. 9651 4.3355 4. 7059 0 .3561 0 .5178 0.9452 0.1637 PSA Diff (1-2) 31 .942 37.312 42 .681 4 .3184 5 .7151 8.4516 2.5559
T-Tests
Variable Method Variances DF t Value Pr > |t]
PSA Pooled Equal 18 14.60 <.0001
PSA Satterthwaite Unequal 9.07 14.60 <-0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PSA Folded F 9 9 242.69 <.0001
Comparison in PSA for KidSton and Parkinso 375
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA KidSton 10 3. 9651 4.3355 4.7059 0.3561 0.5178 0.9452 0.1637
PSA Parkinso 10 11 .998 12.412 12.827 0.3985 0.5793 1.0576 0.1832
PSA Diff (1-2) -8 .593 -8.077 -7.56 0.4151 0.5494 0.8125 0.2457
T-Tests
Variable Method Variances t Value Pr > |t|
PSA Pooled Equal 18 -32.87 <.0001 PSA Satterthwaite Unequal 17.8 -32.87 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PSA Folded F 9 9 1.25 0.7432
Comparison in PSA for Endoaden and Prostate 376
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Endoaden 10 21 .459 34.504 47.55 12 .543 18 .236 33.292 5.7667
PSA Prostate 10 0. 1072 0.2542 0.4012 0. 1414 0. 2055 0.3752 0.065
PSA Diff (1-2) 22 .134 34.25 46.366 9. 7441 12 .896 19.07 5.7671 T-Tests
Variable Method Variances DF t Value Pr > |t|
PSA Pooled Equal 18 5.94 <.0001
PSA Satterthwaite Unequal 9 S.94 0.0002
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PSA Folded F 9 9 7872.16 <.0001
Comparison m PSA for Endoaden and Prostati 377
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Endoaden 10 21. 459 34. 504 47.55 12.543 18.236 33.292 5.7667
PSA Prostati 10 38. 016 40. 419 42.823 2.3108 3.3595 6.1332 1.0S24
PSA Diff (1-2) -18 .23 -5. 915 6.4042 9.9074 13.112 19.39 5.8638
T-Tests
Variable Method Variances t Value Pr > |t|
PSA Pooled Equal 18 -1.01 0.3265 PSA Satterthwaite Unequal 9.61 -1.01 0.3378
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PSA Folded F 9 9 29.46 <.0001
Comparison in PSA for Endoaden and Arthriti 378
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Arthriti 10 13.286 24 .616 35.946 10.894 15.838 28.915 5.0085
PSA Endoaden 10 21.459 34 .504 47.55 12.543 18.236 33.292 5.7667
PSA Diff (1-2) -25.94 -9 .889 6.1585 12 905 17.079 25.257 7.6381
T-Tests
Variable Method Variances t Value
PSA Pooled Equal 18 -1.29 0.2118 PSA Satterthwaite Unequal 17.7 -1.29 0.2121
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PSA Folded F 9 9 1.33 0.6813
Comparison in PSA for Endoaden and Aortic 379
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Aortic 10 35 .877 41. 647 47.417 5. 5479 8. 0657 14.725 2.5506
PSA Endoaden 10 21 .459 34. 504 47.55 12 .543 18 .236 33.292 5.7667
PSA Diff (1-2) -6 .105 7. 143 20.391 10 .654 14.1 20.851 6.3056 T-Tests
Variable Method Variances DF t Value Pr > ItI
PSA Pooled Equal 18 1 13 0 2722
PSA Satterthwaite Unequal 12 4 1 13 0 2787
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PSA Folded F 9 9 S 11 0 0233
Comparison m PSA for Endoaden and Parkmso 380
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Endoaden 10 21 4S9 34 504 47 55 12 543 18 236 33 292 5 7667
PSA Parkmso 10 11 998 12 412 12 827 0 3985 0 5793 1 0576 0 1832
PSA Diff (1-2) 9 9707 22 092 34 214 9 7484 12 901 19 079 5 7696
T-Tests
Variable Method Variances DF t Value Pr » |t|
PSA Pooled Equal 18 3 83 0 0012
PSA Satterthwaite Unequal 9 02 3 83 0 0040
Equality of Variances
Variable Method Num DF Den DF F Value Pr > P
PSA Folded F 9 9 990 86 < 0001
Comparison m PSA for Prostate and Prostati 381
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Prostate 10 0 1072 0 2542 0 4012 0 1414 0 2055 0 3752 0 065
PSA Prostati 10 38 016 40 419 42 823 2 3108 3 3595 6 1332 1 0624
PSA Diff (1-2) -42 4 -40 17 -37 93 1 7984 2 38 3 5196 1 0644
T Tests
Variable Method Variances t Value Pr > |t|
PSA Pooled Equal 18 37 74 0001 PSA Satterthwaite Unequal 9 07 37 74 0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PSA Folded F 9 9 267 18 < 0001
Comparison m PSA for Prostate and Arthriti 382
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Arthriti 10 13 286 24 616 35 946 10 894 15 838 28 915 5 0085 PSA Prostate 10 0 1072 0 2542 0 4012 0 1414 0 2055 0 3752 0 065 PSA Diff (1-2) 13 838 24 362 34 885 8 4631 11 2 IS 563 5 0089 T-Tests
Variable Method Variances DF t Value Pr >
PSA Pooled Equal 18 4.86 0. 0001 PSA Satterthwaite Unequal 9 4.86 0.ooos
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
PSA Folded F 9 9 5938.19 <.0001
Comparison in PSA for Prostate and Aortic 383
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Aortic 10 35 .877 41 .647 47.417 5 .5479 8 .0657 14.725 2.5506 PSA Prostate 10 0. 1072 0. 2542 0.4012 0 .1414 0 .2055 0.3752 0.065 PSA Diff (1-2) 35 .033 41 .393 46.753 4 .3109 5 .7052 8.437 2.5514
T-Tests
Variable Method Variances t Value Pr >
PSA Pooled Equal 18 16.22 ■c.OOOl PSA Satterthwaite Unequal 9.01 16.22 <.oooi
Equality of Variances -
Variable Method Num DF Den DF F Value Pr > F
PSA Folded F 9 9 1540.02 <.0001
Comparison in PSA for Prostate and Parkinso 384
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Parkinso 10 11.998 12.412 12.827 0.3985 0.5793 1.0576 0.1832
PSA Prostate 10 0.1072 0.2542 0.4012 0.1414 0.2055 0.3752 0.065
PSA Diff (1-2) 11.75 12.158 12.566 0.3284 0.4347 0.6428 0.1944
T-Tests
Variable Method Variances t Value Pr > |t|
PSA Pooled Equal 18 62.54 <.0001 PSA Satterthwaite Unequal 11.2 62.54 <.oooi
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PSA Folded F 9 9 7.94 0.0050
Comparison in PSA for Prostati and Arthriti 385
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Arthriti 10 13. 286 24.616 35 .946 10.894 15 .838 28.915 5.0085
PSA Prostati 10 38. 016 40.419 42 .823 2.3108 3. 3595 6.1332 1.0624
PSA Diff (1-2) -26 .56 -15.8 -5 .047 8.6507 11 .449 16.93 5.1199 T-Tests
Variable Method Variances DF t Value Pr =. |t|
PSA Pooled Equal 18 -3.09 0.0064 PSA Satterthwaite Unequal 9.81 -3.09 0.0118
Equality of Variances
Variable Method Num DF Den DF F Value Pr > P
PSA Folded F 9 9 22.23 <.0001
Comparison in PSA for Prostati and Aortic 386
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Aortic 10 35 .877 41 .547 47.417 5.5479 8.0657 14.725 2.5506
PSA Prostati 10 38 .016 40 .419 42.823 2.3108 3.3395 6.1332 1.0S24
PSA Diff (1-2) -4 .577 1. 2279 7.0328 4.6684 6.1783 9.1366 2.763
T-Tests
Variable Method Variances DF t Value Pr > |t|
PSA Pooled Equal 18 0.44 0.6620 PSA Satterthwaite Unequal 12 0.44 0.6646
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F
PSA Folded F 9 9 5.76 0.0155
Comparison in PSA for Prostati and Parkinso 387
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Parkmso 10 11 .998 12.412 12. 827 0 .3985 0.5793 1.0576 0.1832 PSA Prostati 10 38 .016 40.419 42. 823 2 .3108 3.3595 6.1332 1.0624 PSA Diff (1-2) -30.27 -28.01 -25 .74 1 .8215 2.4106 3.5649 1.0781
T-TeStS
Variable Method Variances DF t Value Pr > |t|
PSA Pooled Equal 18 -25 .98 «.0001
PSA Satterthwaite Unequal 9 .53 -25 .98 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PSA Folded F 9 9 33.63 <.0001
Comparison in PSA for Arthriti and Aortic 388
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Aortic 10 35.877 41.647 47.417 5. 5479 8. 0657 14.725 2.5506 PSA Arthriti 10 13.286 24.616 35.946 10 .894 15 .838 28.915 5.0085 PSA Diff (1-2) 5.2231 17.032 28.84 9. 4965 12 .568 18.586 5.6206 T-Tests
Variable Method Variances DF t Value Pr > |t|
PSA Pooled Equal 18 3.03 0.0072
PSA Satterthwaite Unequal 13.4 3.03 0.0094
Equality of Variances
Variable Method Num DF Den DF P Value Pr > F
PSA Folded F 9 9 3.8S 0.0570
Comparison in PSA for Arthriti and Parkinso 389
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Arthriti 10 13 .286 24 .61S 35.946 10.894 15.838 28.915 5.0085
PSA Parkinso 10 11 .998 12 .412 12.827 0.3985 0.5793 1.0576 0.1832
PSA Diff (1-2) 1. S742 12 .204 22.733 8.468 11.207 16.573 5.0119
T-Tests
Variable Method Variances DF t Value Pr > ]t|
PSA Pooled Equal 18 2.43 0.0255 PSA Satterthwaite Unequal 9.02 2.43 0.0376
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PSA Folded F 9 9 747.43 <.0001
Comparison in PSA for Aortic and Parkinso 390
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
PSA Aortic 10 35. .877 41 .647 47 .417 5 .5479 8.0657 14.725 2 .5506 PSA Parkinso 10 11.998 12.412 12.827 0.3985 0.5793 1.0576 0.1832 PSA Diff (1-2) 23.863 29.235 34.608 4.3206 5.718 8.456 2.5572
T-Tests
Variable Method Variances DF t Value Pr > |t|
PSA Pooled Equal 18 11. .43 < .0001 PSA Satterthwaite Unequal 9.09 11.43 < .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
PSA Folded F 9 9 193.84 <.0001
Comparison in Labvision Tgase 2 for Cstitis and Kidston 391
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Cstitis 10 2.0932 9 .0974 16.102 6.7347 9 .7912 17.875 3.0962
Lab KidSton 9 -0.903 2 .6482 6.1993 3.1204 4 .6197 8.8503 1.5399
Lab Diff (1-2) -1.109 6 .4492 14.008 5.8509 7 .7972 11.689 3.5826 T-Tests
Variable Method Variances DF t Value Pr > |t|
Lab Pooled Equal 17 1.80 0 .0896 Lab Ξatterthwaite Unequal 13.1 1.86 0.0847
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F Lab Folded F 9 8 4.49 0.0458
Comparison in Labvision Tgase 2 for Ostitis and Endoaden 392
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Cstitis 10 2.0932 9.0974 16.102 6.7347 9.7912 17.875 3.09S2 Lab Endoaden 10 1.1332 3.2846 5.436 2.0686 3.0074 5.4904 0.951 Lab Diff (1-2) -0.992 5.8128 12.618 5.4726 7.2426 10.711 3.239
T-Tests Variable Method Variances DF t Value Pr > 111
Lab Pooled Equal 18 1.79 0.0895
Lab Satterthwaite Unequal 10.7 1.79 0.1010
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F Lab Folded F 9 9 10.60 0.0017
Comparison in Labvision Tgase 2 for Cstitis and Prostate 393
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N N M Meeaann M Meeaann Mean Std Dev std Dev Std Dev Std Err
Lab Cstitis 1 100 22.. . .00993322 9 9 . .00997744 16 .102 6 .7347 9.7912 17.8 3.0962
Lab Prostate 1 100 00 . .00228866 1 1 . .11221166 2. 2146 1.051 1.5279 2.78 0.4832
Lab Diff (1-2) 1 1.. . .33992211 7 7 . .99775588 14 .559 5 .2947 7.0072 10.3 3.1337
T-Tests
Variable Method Variances DF t Value Pr » ItI
Lab Pooled Equal 18 2.55 0 .0203
Lab Satterthwaite Unequal 9 .44 2.55 0 .0304
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 9 9 ' 41.06 <.0001
Comparison in Labvision Tgase 2 for Cstitis and Prostati 394
The TTEST Procedure
Statistics
Lower CL Upper CL jower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Cstitis 10 2.0932 9.0974 1 166. .110022 6 .7347 9 .7912 17 .875 3 .0962
Lab Prostati 10 0.1682 0.4647 0 0..7 7661122 0 .2851 0 .4145 0. 7568 0 .1311
Lab Diff (1-2) 2.1219 8.6327 1 155. .114433 5 .2361 6 .9296 10 .248 3.099 T-Tests
Variable Method Variances DF t Value Pr > It=I
Lab Pooled Equal 18 2.79 0. 0122
Lab Satterthwaite Unequal 9.03 2.79 0.0211
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 9 9 557.92 <.0001
Comparison in Labvision Tgase 2 for Ostitis and Arthriti 395
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev std Dev Std Dev Std Err
Lab Arthriti 10 0.2488 0 .4395 0.S302 0.1834 0.266S 0.4868 0.0843
Lab Cstitis 10 2.0932 9 .0974 15.102 6.7347 9.7912 17.875 3.0962
Lab Diff (1-2) -15.17 _ 8.658 -2.151 5.2333 6.926 10.242 3.0974
T-Tests
Variable Method Variances DF t Value Pr > |t|
Lab Pooled Equal 18 -2.80 0.0120 Lab Satterthwaite Unequal 9.01 -2.80 0.0208
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 9 9 1348.45 <.0001
Comparison in Labvision Tgase 2 for Cstitis and Aortic 396
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab tic 10 0.8782 1. 0367 1. 1952 0 .1524 0.2216 0.4045 0 .0701 Lab itis 10 2.0932 9. 0974 16 .102 6 .7347 9.7912 17.875 3 .0962 Lab f (1-2) -14.57 -8 .061 -1 .554 5 .2327 6.9252 10.241 3.097
T-Tests
Variable Method Variances DF t Value Pr » |t|
Lab Pooled Equal 18 -2.60 0 .0180
Lab Satterthwaite Unequal 9 .01 -2.60 0 .0286
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 9 9 1953.05 <.0001
Comparison in Labvision Tgase 2 for Cstitis and Parkinso 397
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Cstitis 10 2 .0932 9.0974 16.102 6.7347 9.7912 17.875 3.0962 Lab Parkinso 10 0. .3761 0.4616 0.5471 0.0822 0.1195 0.2182 0.0378 Lab Diff (1-2) 2 .1304 8.6358 15.141 5.2318 6.9239 10.239 3.0965 T-Tests
Variable Method Variances DF t Value Pr > |t|
Lab Pooled Equal 18 2 79 0 0121
Lab Satterthwaite Unequal 9 2 79 0 0211
Equality of Variances
Variable Method Num DP Den DF F Value Pr > F
Lab Folded F 9 9 6713 13 < 0001
Comparison in Labvision Tgase 2 for KidSton and Endoaden 398
The TTEST Piocedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Sta Dev Std Dev Std Err
Lab Endoaden 10 1 1332 3 2845 S 436 2 0686 3 0074 S 4904 0 951 Lab KidSton 9 0 903 2 6482 6 1993 3 1204 4 6197 8 8503 1 5399 Lab Diff (1-2) -3 097 0 6364 4 3697 2 8899 3 8512 S 7735 1 7695
T-Tests
Variable Method Variances DF t Value Pr > ItI
Lab Pooled Equal 17 0 36 0 7235 Lab Satterthwaite Unequal 13 5 0 35 0 7306
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 8 9 2 36 0 2228
Comparison m Labvision Tgase 2 for KidSton and Prostate 399
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab KidSton 9 -0 903 2 6482 6 1993 3 1204 4 6197 8 8503 1 5399 Lab Prostate 10 0 (3286 1 1216 2 2146 1 051 1 5279 2 7894 0 4832 Lab Diff (1-2) -1 129 1 5266 4 7823 2 5201 3 3584 5 0348 1 5431
T-Tests
Variable Method Variances DF t Value Pr > lt|
Lab Pooled Equal 17 0 99 0 3364 Lab Satterthwaite Unequal 9 57 0 95 0 3675
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 8 9 9 14 0 0032
Comparison in Labvision Tgase 2 for KidSton and Prostati 400
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab KidSton 9 -0 903 2 6482 6 1993 3 1204 4 6197 8 8503 1 5399 Lab Prostati 10 0 1682 0 4647 0 7612 0 2851 0 4145 0 7568 0 1311 Lab Diff (1-2) -0 902 2 1835 5 2695 2 3888 3 1834 4 7724 1 4627 T-Tests
Variable Method Variances DF t Value Pr > ItI
Lab Pooled Equal 17 1.49 0 .1538 Lab Satterthwaite Unequal 8.12 1.41 0.1949
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 8 9 124.20 < 0001
Comparison in Labvision Tgase 2 for KidSton and Arthriti 401
The TTEST Procedure
Statistics
Lower CL Upper CL jower CL Upper CL
Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Arthriti 10 0. 2488 0. 4395 0.6302 0.1834 0.2666 0.4868 0.0843 Lab KidSton 9 -0 .903 2. 6482 6.1993 3.1204 4.6197 8.8503 1.5399 Lab Diff (1-2) -5 .287 -2 .209 0.8691 2.3825 3.175 4.7598 1.4588
T-Tests
Variable Method Variances t Value Pr > |t|
Lab Pooled Equal 17 -1.51 0.1484 Lab Satterthwaite Unequal 8.05 -1.43 0.1898
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 8 9 300.19 <.0001
Comparison m Labvision Tgase 2 for KidSton and Aortic 402
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Aortic 10 0. 8782 1. 0367 1.1952 0.1524 0.2216 0.4045 0.0701
Lab KidSton 9 -0 .903 2. 6482 6.1993 3.1204 4.6197 8.8503 1.5399
Lab Diff (1-2) -4 .688 -1 .612 1.4646 2.3811 3.1732 4.7571 1.458
T-Tests
Variable Method Variances t Value Pr > |t|
Lab Pooled Equal 17 -1.11 0.2844 Lab Satterthwaite Unequal 8.03 -1.05 0.3263
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 8 9 434.79 <.0001
Comparison m Labvision Tgase 2 for KidSton and Parkmso 403
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab KidSton 9 -0 .903 2 .6482 6 .1993 3 .1204 4 .6197 8.8503 1.5399
Lab Parkmso 10 0. 3761 0 .4616 0 .5471 0 .0822 0 .1195 0.2182 0.0378
Lab Diff (1-2) -0 .887 2 .1866 5 .2599 2.379 3 .1703 4.7527 1.4567 T-Tests
Variable Method Variances DF t Value Pr > |t|
Lab Pooled Equal 17 1.50 0.1517
Lab Satterthwaite Unequal 8.01 1.42 0.1935
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 8 9 1494.48 <.0001
Comparison in Labvision Tgase 2 for Endoaden and Prostate 404
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Endoaden 10 1.1332 3.2846 5.436 2.0686 3.0074 5.4904 0.951
Lab Prostate 10 0.0286 1.1216 2.2146 1.051 1.5279 2.7894 0.4832 Lab Diff (1-2) -0.078 2.163 4.4041 1.8023 2.3853 3.5274 1.0667
T-Tests
Variable Method Variances DP t Value Pr > |t|
Lab Pooled Equal 18 2.03 0.0577 Lab Satterthwaite Unequal 13.4 2.03 0.0630
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 9 9 3.87 0.0562
Comparison in Labvision Tgase 2 for Endoaden and Prostati 405
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev- Std Dev Std Dev Std Err
Lab Endoaden 10 1 .1332 3 .2846 5.436 2 .0686 3.0074 5. .4904 0.951
Lab Prostati 10 0 .1682 0 .4647 0.7612 0 .2851 0.4145 0 .7568 0.1311
Lab Diff (1-2) 0.803 2 .8199 4.8368 1 .6221 2.1467 3 .1745 0.96
T-Tests
Variable Method Variances DF t Value Pr > |t|
Lab Pooled Equal 18 2.94 0 .0088
Lab Satterthwaite Unequal 9 .34 2.94 0 .0159
Equality of Variances
Variable Method Num DF Den DF F Value Pr > P
Lab Folded F 9 9 52.64 <.0001
Comparison in Labvision Tgase 2 for Endoaden and Arthriti 406
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Arthriti 10 0.2488 0.4395 0.6302 0 .1834 0 .2666 0 .4868 0.0843 Lab Endoaden 10 1.1332 3.2846 5.436 2 .0686 3 .0074 5 .4904 0.951 Lab Diff (1-2) -4.851 -2.845 -0.839 1 .6132 2 .1349 3 .1572 0.9548 T-Tests
Variable Method Variances DF t Value Pr > 111
Lab Pooled Equal 18 -2.98 0 0080 Lab Satterthwaite Unequal 9.14 -2.98 0 0152
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 9 9 127.22 <.0001
Comparison m Labvision Tgase 2 for Endoaden and Aortic 407
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Aortic 10 0.8782 1.03S7 1.1952 0.1524 0.2216 0.4045 0.0701
Lab Endoaden 10 1.1332 3.2846 5.436 2.0686 3.0074 5.4904 0.951
Lab Diff (1-2) -4.251 -2.248 -0.244 1.6112 2.1323 3.1533 0.9536
T-Tests
Variable Method Variances DF t Value Pr > |t|
Lab Pooled Equal 18 -2.36 0.0299 Lab Satterthwaite Unequal 9.1 -2.36 0.0425
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 9 9 184.26 <.0001
Comparison in Labvision Tgase 2 for Endoaden and Parkmso 408
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab oaden 10 1 .1332 3 .2846 5.436 2 .0586 3.0074 5.4904 0 .951 Lab kmso 10 0 .3761 0 .4616 0.5471 0 .0822 0.1195 0.2182 0. 0378 Lab f (1-2) 0 .8234 2.823 4.8226 1 .6081 2.1282 3.1473 0. 9518
T-Tests
Variable Method Variances DF t Value Pr > |t|
Lab Pooled Equal 18 2 .97 0 .0083
Lab Satterthwaite Unequal 9 .03 2 .97 0 .0158
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 9 9 633.35 <.0001
Comparison m Labvision Tgase 2 for Prostate and Prostati 409
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Prostate 10 0. 0286 1 .1216 2 .2146 1.051 1 .5279 2 .7894 0 .4832
Lab Prostati 10 0. 1682 0 .4647 0 .7612 0 .2851 0 .4145 0 .7568 0 .1311
Lab Diff (1-2) -0 .395 0 .6569 1 .7087 0 .8459 1 .1195 1 .6555 0 .5006 T-Tests
Variable Method Variances DF t Value Pr > |t|
Lab Pooled Equal 18 1.31 0.2060
Lab Satterthwaite Unequal 10.3 1.31 0.2179
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 9 9 13.59 0.0006
Comparison in Labvision Tgase 2 for Prostate and Arthriti 410
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab hriti 10 0.2488 0. 4395 0.6302 0 .1834 0.2666 0.4868 0 .0843 Lab ■state 10 0.0286 1. 1216 2.2146 1.051 1.5279 2.7894 0 .4832 Lab f (1-2) -1.713 -0 .682 0.3483 0 .8287 1.0967 1.6219 0 .4905
T-Tests
Variable Method Variances DF t Value Pr > |t|
Lab Pooled Equal 18 -1.39 0 .1813
Lab Satterthwaite Unequal 9 .55 -1.39 0 .1959
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 9 9 32.84 <.0001
Comparison in Labvision Tgase 2 for Prostate and Aortic 411
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Aortic 10 0.8782 1.0367 1.1952 0.1524 0.2216 0.4045 0.0701
Lab Prostate 10 0.0286 1.1216 2.2146 1.051 1.5279 2.7894 0.4832
Lab Diff (1-2) -1.111 -0.085 0.9408 0.8249 1.0917 1.6144 0.4882
T-Tests
Variable Method Variances DF t Value Pr > |t|
Lab Pooled Equal 18 -0.17 0.8639 Lab Satterthwaite Unequal 9.38 -0.17 0.8656
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 9 9 47.56 <.0001
Comparison in Labvision Tgase 2 for Prostate and Parkinso 412
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Parkinso 10 0. 3761 0 .4616 0 .5471 0.0822 0 .1195 0 .2182 0 .0378
Lab Prostate 10 0. 0286 1 .1216 2 .2146 1.051 1 .5279 2 .7894 0 .4832
Lab Diff (1-2) -1 .678 -0.66 0 .3582 0.8189 1 .0837 1 .6026 0 .4846 T Tests
Variable Method Variances DF t Value Pr > |t|
Lab Pooled Equal 18 -1 36 0 1901
Lab Satterthwaite Unequal 9 11 -1 36 0 2060
Equality of Variances
Variable Method Num DP Den DF F Value Pr > F
Lab Folded F 9 9 163 48 < 0001
Comparison m Labvision Tgase 2 for Prostati and Arthnti 413
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Arthnti 10 0 2488 0 4395 0 6302 0 1834 0 2666 0 4868 0 0843
Lab Prostati 10 0 1682 0 4647 0 7612 0 2851 0 4145 0 7568 0 1311
Lab Diff (1-2) -0 353 -0 025 0 3022 0 2633 0 3485 0 5154 0 1559
T-Tests
Variable Method Variances DF t Value Pr > ]t|
Lab Pooled Equal 18 -0 16 0 8734 Lab Satterthwaite Unequal 15 4 -0 16 0 8737
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 9 9 2 42 0 2048
Comparison m Labvision Tgase 2 for Prostati and Aortic
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Aortic 10 0 8782 1 0367 1 1952 0 1524 0 2216 0 4045 0 0701 Lab Prostati 10 0 1682 0 4647 0 7612 0 2851 0 4145 0 7568 0 1311 Lab DiEf (1-2) 0 2597 0 572 0 8843 0 2511 0 3324 0 4915 0 1486
T-Tests
Variable Method Variances DF t Value Pr > t
Lab Pooled Equal 18 3 85 0 0012 Lab Satterthwaite Unequal 13 8 3 85 0 0018
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 9 9 3 50 0 0760
Comparison in Labvision Tgase 2 for Prostati and Parkmso 415
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Parkmso 10 0 3761 0 4616 0 5471 0 0822 0 1195 0 2182 0 0378
Lab Prostati 10 0 1682 0 4647 0 7612 0 2851 0 4145 0 7568 0 1311
Lab Diff (1-2) -0 29 -0 003 0 2835 0 2305 0 305 0 4511 0 1364 T-Tests
Variable Method Variances DF t Value Pr > |t|
Lab Pooled Equal 18 -0.02 0.9821
Lab Satterthwaite Unequal 10.5 -0.02 0.9823
Equality of Variances
Variable Method Num DP Den DF F Value Pr > F
Lab Folded F 9 9 12.03 0.0010
Comparison in Labvision Tgase 2 for Arthriti and Aortic 41S
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Aortic 10 0 .8782 1 .0367 1 .1952 0 .1524 0 .2216 0.4045 0.0701 Lab Arthriti 10 0 .2488 0 .4395 0 .6302 0 .1834 0 .2666 0.4868 0.0843 Lab Diff (1-2) 0 .3669 0 .5972 0 .8275 0 .1852 0 .2451 0.3625 0.1096
T-Tests
Variable Method Variances t Value Pr > |t|
Lab Pooled Equal 18 5.45 <.oooi Lab Satterthwaite Unequal 17.4 5.45 <.0001
Equality of Variances
Variable Method Num DF Den DF P Value Pr > F
Lab Folded F 9 9 1.45 0.5899
Comparison in Labvision Tgase 2 for Arthriti and Parkinso
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Arthriti 10 0.2488 0. 4395 0.6302 0. .1834 0.2666 0.4868 0. 0843 Lab Parkinso 10 0.3761 0.4616 0.5471 0..0822 0.1195 0.2182 0.0378 Lab Diff (1-2) -0.216 -0.022 0.172 0..1561 0.2066 0.3055 0.0924
T-Tests
Variable Method Variances DF t Value Pr > |t|
Lab Pooled Equal 18 -0.24 0.8137 Lab Satterthwaite Unequal 12.5 -0.24 0.8148
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 9 9 4.98 0.0254
Comparison in Labvision Tgase 2 for Aortic and Parkinso 418
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Lab Aortic 10 0 .8782 1 .0367 1 .1952 0 .1524 0 .2216 0 .4045 0 .0701
Lab Parkinso 10 0 .3761 0 .4616 0 .5471 0 .0822 0 .1195 0 .2182 0 .0378
Lab Diff (1-2) 0 .4079 0 .5751 0 .7423 0 .1345 0.178 0 .2632 0 .0796 T-Tests
Variable Method Variances DF t Value Pr > |t|
Lab Pooled Equal 18 7.22 < .0001
Lab Satterthwaite Unequal 13.8 7.22 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Lab Folded F 9 9 3.44 0.0801
Comparison in Aquaponn-4 for Cstitis and Kidston 419
The TTEST Procedure Statistics
Lower CL Upper CL Lower CIJ Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Cstitis 9 75.34 285.87 496.4 185 273 .89 524.71 91.297
Aqua KidSton 10 46.678 54.239 61.799 7.2697 10. 569 19.295 3.3422
Aqua Diff (1-2) 49.343 231.63 413.92 141.11 188 .04 281.91 86.4
T-Tests
Variable Method Variances t Value Pr >
Aqua Pooled Equal 17 2.68 0.0158 Aqua Satterthwaite Unequal 8.02 2.54 0.0349
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 8 9 671.57 <.0001
Comparison in Aquapoπn-4 for Cstitis and Endoaden 420
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Cstitis 75.34 285.87 496.4 185 273.89 524.71 91.297 Aqua Endoaden 232.32 480 727.68 195.88 296.26 602.97 104.74 Aqua Diff (1-2) -488.8 -194.1 100.58 210.2 284.55 440.39 138.27
T-Tests
Variable Method Variances t Value Pr > |t|
Aqua Pooled Equal 15 -1.40 0.1807 Aqua Satterthwaite Unequal 14.4 -1.40 0.1835
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 7 8 1.17 0.8225
Comparison in Aquaporin-4 for Cstitis and Prostate 421
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Cstitis 9 75.34 285 .87 496.4 185 273 .89 524.71 91.297
Aqua Prostate 10 0.1329 0. 492 0.8511 0.3453 0. 502 0.9164 0.1587
Aqua Diff (1-2) 103.24 285 .38 467.51 140.99 187 .89 281.67 86.328 T-Tests
Variable Method Variances DF t Value Pr > |t|
Aqua Pooled Equal 17 3 31 0 0042 Aqua Satterthwaite Unequal 8 3 13 0 0141
Equality of Variances
Variable Method Mum DF Den DF F Value Pr > F
Aqua Folded F 8 9 297721 <.0001
Comparison m Aquaporm-4 for Ostitis and Prostati
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev std Dev Std Dev Std Err
Aqua Ostitis 9 75.34 285 87 496 4 185 273.89 524 71 91 297
Aqua Prostati 10 238.33 413.84 589.35 168.76 245 35 447.92 77 587
Aqua Diff (1-2) -379.2 -128 123 27 194.48 259 17 388.54 119.08
T-Tests
Variable Method Variances t Value Pr > |t|
Aqua Pooled Equal 17 -1.07 0 2976 Aqua Satterthwaite Unequal 16.2 -1.07 0.3011
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 8 9 1.25 0 7452
Comparison in Aquaporm-4 for Cstitis and Arthriti 423
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Arthriti 10 363.49 506 92 650 35 137.91 200.5 366.04 63.404 Aqua Ostitis 9 75.34 285.87 496.4 185 273 89 524.71 91.297 Aqua Diff (1-2) -9.546 221.05 451.64 178.5 237.87 356.61 109.3
T-Tests
Variable Method Variances t Value Pr > |t|
Aqua Pooled Equal 17 2.02 0.0592 Aqua Satterthwaite Unequal 14.6 1.99 0 0659
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 8 9 1.87 0.3715
Comparison m Aquaporm-4 for Cstitis and Aortic 424
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Aortic 10 165.4 344 .57 523.75 172.28 250 .47 457.26 79.206
Aqua Cstitis 9 75.34 285 .87 496.4 185 273 .89 524.71 91.297
Aqua Diff (1-2) -195 58. 702 312.44 196.42 261 .75 392.41 120.27 T Tests
Variable Method Variances DF t Value Pr » ItI
Aqua Pooled Equal 17 0 49 0 S317 Aqua Satterthwaite Unequal 16 3 0 49 0 S336
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 8 9 1 20 0 7898
Comparison m Aquaporm-4 for Ostitis and Parkmso 425
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Cstitis 9 75 34 285 87 496 4 185 273 89 524 71 91 297
Aqua Parkmso 10 85 402 88 731 92 061 3 2016 4 6546 8 4974 1 4719
Aqua Diff (1-2) 14 973 197 14 379 3 141 01 187 92 281 72 86 342
T-Tests
Variable Method Variances DF t Value Pr > |t|
Aqua Pooled Equal 17 2 28 0 0356 Aqua Satterthwaite Unequal 2 16 0 0S29
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 8 9 3462 53 < 0001
Comparison in Aquaponn 4 for KidSton and Endoaden 426
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Endoaden 8 232 32 480 727 68 195 88 296 26 602 97 104 74 Aqua KidSton 10 46 678 54 239 61 799 7 2697 10 569 19 295 3 3422 Aqua Diff (1-2) 228 55 425 76 622 97 146 06 196 12 298 48 93 028
T-Tests
Variable Method Variances DF t Value Pr > |t|
Aqua Pooled Equal 16 4 58 0 0003 Aqua Satterthwaite Unequal 7 01 4 06 0 0048
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 7 9 785 77 < 0001
Comparison in Aquaporm-4 for KidSton and Prostate 427
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua KidSton 10 46 678 54 239 61 799 7 2697 10 569 19 295 3 3422
Aqua Prostate 10 0 1329 0 492 0 8511 0 3453 0 502 0 9164 0 1587
Aqua Diff (1-2) 46 717 53 747 60 776 5 6533 7 4818 11 064 3 3459 T-Tests
Variable Method Variances DF t Value Pr >
Aqua Pooled Equal 18 16.06 «.0001 Aqua Satterthwaite Unequal 9.04 16.06 <.oooi
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 9 9 443.32 <.0001
Comparison in Aquaponn-4 for KidSton and Prostati 42S
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua KidSton 10 46.678 54.239 61.799 7.2697 10. 569 19.295 3. 3422 Aqua Prostati 10 238.33 413.84 589 35 168.76 245 .35 447.92 77 .587 Aqua Diff (1-2) -522.8 -359.6 -196.4 131.21 173 .65 256.8 77 .659
T-Tests
Variable Method Variances DF t Value Pr > ItI
Aqua Pooled Equal 18 -4.63 0 .0002 Aqua Satterthwaite Unequal 9 .03 -4.63 0 .0012
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 9 9 538.92 <.0001
Comparison m Aquaponn-4 for KidSton and Arthriti 429 r r
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Arthriti 10 363.49 506 .92 650.35 137.91 200.5 366.04 63.404
Aqua KidSton 10 46.678 54. 239 61.799 7.2697 10.569 19.295 3.3422
Aqua Diff (1-2) 319.29 452 .68 586.07 107.28 141.97 209.95 63.492
T-Tests
Variable Method Variances DF t Value Pr > |t]
Aqua Pooled Equal 18 7.13 <.0001 Aqua Satterthwaite Unequal 9.05 7.13 <.0001
Equality of Variances
Variable Method Num DF Den DP F Value Pr > F
Aqua Folded F 9 9 359.89 <.0001
Comparison m Aquaporm-4 for KidSton and Aortic 430
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Aortic 10 165.4 344.57 523 .75 172.28 250.47 457 .26 79 .206 Aqua KidSton 10 46.678 54.239 61. 799 7.2697 10.569 19. 295 3. 3422 Aqua Diff (1-2) 123.78 290.33 456 .89 133.95 177.27 262 .15 79 .277 T-Tests
Variable Method Variances DF t Value Pr > |t]
Aqua Pooled Equal 18 3.66 0.0018 Aqua Satterthwaite Unequal 9.03 3.66 0.0052
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 9 9 561.64 <.0001
Comparison in Aquaporin-4 for KidSton and Parkinso 431
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua KidSton 10 46.678 54.239 61.799 7.2697 10.569 19.295 3.3422
Aqua Parkinso 10 85.402 88.731 92.061 3.2016 4.6546 8.4974 1.4719
Aqua Diff (1-2) -42.16 -34.49 -26.82 6.1703 8.166 12.076 3.6519
T-Tests
Variable Method Variances t Value Pr > |t|
Aqua Pooled Equal 18 -9.44 <.0001 Aqua Satterthwaite Unequal 12.4 -9.44 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 9 9 5.16 0.0226
Comparison in Aquaporin-4 for Endoaden and Prostate 432
The TTEST Procedure
Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Endoaden 8 8 223322..3322 4 48800 772277. .6688 1 19955.. .8888 2 29966 . .2266 602.97 104.74
Aqua Prostate 1 100 00..11332299 0 0..449922 00..88551111 0 0..33445533 0 0.. 5 50022 0.9164 0.1587
Aqua Diff (1-2) 2 28822..4466 4 47799..5511 667766. .5566 1 14455., .9944 1 19955 . .9966 298.24 92.952
T-Tests
Variable M Meetthhoodd VVaarriiaanncceess DDFF tt VVaalluuee Pr > |t|
Aqua PPoooolleedd EEqquuaall 1166 55..1166 <.0001
Aqua SSaatttteerrtthhwwaaiittee UUnneeqquuaall 77 44..5588 0.0026
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F Aqua Folded F 7 9 348347 <.0001
Comparison in Aquaporin-4 for Endoaden and Prostati 433
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Endoaden 8 232.32 480 727.68 195. 88 296 .26 602 .97 104 .74 Aqua Prostati 10 238.33 413.84 589.35 168. 76 245 .35 447 .92 77. 587 Aqua Diff (1-2) -204.1 66.16 336.47 200 .2 268 .81 409 .12 127 .51 T Tests
Variable Method Variances DF t Value Pr > |t|
Aqua Pooled Equal 16 0 52 0 6110 Aqua Satterthwaxte Unequal 13 6 0 51 0 6199
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F Aqua Folded F 7 9 1 46 0 5854
Comparison m Aquaporm 4 for Endoaden and Arthriti 434
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL Variable Disease N Mean Mean Mean Std Dev Std Dev std Dev Std Err
Aqua Arthriti 10 363 49 506 92 650 35 137 91 200 5 366 04 63 404 Aqua Endoaden 8 232 32 480 727 68 195 88 296 26 602 97 104 74 Aqua Dlff (1-2) -221 5 26 918 275 3 183 96 247 01 375 93 117 17
T Tests Variable Method Variances DF t Value Pr > 111
Aqua Pooled Equal 16 0 23 0 8212 Aqua Satterthwaite Unequal 11 8 0 22 0 8297
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F Aqua Folded F 7 9 2 18 0 2731
Comparison in Aquapoπn-4 for Endoaden and Aortic 435
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Aortic 10 165 4 344 57 523 75 172 28 250 47 457 26 79 206 Aqua Endoaden 8 232 32 480 727 68 195 88 296 26 602 97 104 74 Aqua Dlff (1-2) 408 4 -135 4 137 54 202 17 271 46 413 14 128 76
T-Tests Variable Method Variances DF t Value Pr > |t|
Aqua Pooled Equal 16 -1 OS 0 3085
Aqua Satterthwaite Unequal 13 8 -1 03 0 3202
Equality of Variances
Variable Method Nura DF Den DF F Value Pr > F Aqua Folded F 7 9 1 40 0 6249
Comparison in Aquaporm-4 for Endoaden and Parkmso 436
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Endoaden 8 232 32 480 727 68 195 88 296 26 602 97 104 74 Aqua Parkmso 10 85 402 88 731 92 061 3 2016 4 6546 8 4974 1 4719 Aqua Dlff (1-2) 194 19 391 27 588 35 145 97 195 99 298 28 92 966 T-Tests
Variable Method Variances DF t Value Pr > |t|
Aqua Pooled Equal 16 4.21 0 0007 Aqua Satterthwaite Unequal 7 3 74 0 0073
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 7 9 4051 31 < 0001
Comparison m Aquaponn-4 for Prostate and Prostati 437
The TTEST Procedure Statistics
Lower CL Upper CL Lower CD Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Prostate 10 0.1329 0.492 0.8511 0.3453 0.502 0.9164 0.1587 Aqua Prostati 10 238.33 413 84 589.35 168 76 245.35 447.92 77.587 Aqua Diff (1-2) -576.4 -413 3 -250.3 131.09 173.49 256.56 77.587
T-Tests
Variable Method Variances DF t Value Pr > |t|
Aqua Pooled Equal 18 -5.33 <.0001 Aqua Satterthwaite Unequal 9 -5 33 0.0005
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 9 9 238912 <.0001
Comparison m Aquapoπn-4 for Prostate and Arthriti 438
The TTEST Procedure Statistics
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Arthriti 10 363.49 506.92 650.35 137.91 200 5 356 04 63.404 Aqua Prostate 10 0.1329 0.492 0 8511 0.3453 0.502 0.9164 0.1587 Aqua Diff (1-2) 373.22 506.43 639.63 107.13 141.78 209.66 63 404
T-Tests
Variable Method Variances DF t Value Pr > |t|
Aqua Pooled Equal 18 7.99 < 0001 Aqua Satterthwaite Unequal 9 7.99 < .0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 9 9 159547 <.0001
Comparison in Aquaponn-4 for Prostate and Aortic 439
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Aortic 10 165.4 344 .57 523.75 172.28 250 .47 457.26 79.206
Aqua Prostate 10 0.1329 0. 492 0.8511 0.3453 0. 502 0.9164 0.1587
Aqua Diff (1-2) 177.67 344 .08 510.49 133.83 177 .11 261 92 79.206 T-Tests
Variable Method Variances DF t Value Pr > 1t1
Aqua Pooled Equal 18 4.34 0.0004 Aqua Satterthwaite Unequal 9 4.34 0.0019
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 9 9 248988 <.0001
Comparison in Aquaporin-4 for Prostate and Parkinso
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Parkinso 10 85.402 88 .731 92 .061 3 .2016 4.6S46 8.4974 1.4719 Aqua Prostate 10 0.1329 0.492 0.8511 0.3453 0.502 0.9164 0.1587 Aqua Diff (1-2) 85.129 88.239 91.349 2.5013 3.3104 4.8954 1.4804
T-Tests
Variable Method Variances DF t Value Pr ^ |t|
Aqua Pooled Equal 18 59.60 <.0001 Aqua Satterthwaite Unequal 9.21 59.60 <.0001
Equality of Variances
Variable Method Num DF Den DF ' F Value Pr > F
Aqua Folded F 9 9 85.98 <.0001
Comparison in Aquaporin-4 for Prostati and Arthriti 441
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std En
Aqua Arthriti 10 3S3.49 506.92 650. .35 137.91 200 .5 366.04 63.404 Aqua Prostati 10 238.33 413.84 589..35 168.76 245.35 447.92 77.587 Aqua Diff (1-2) -117.4 93.078 303..59 169.3 224.05 331.33 100.2
T-Tests
Variable Method Variances DF t Value Pr > |t|
Aqua Pooled Equal 18 0.93 0.3652 Aqua Satterthwaite Unequal 17.3 0.93 0.3657
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 9 9 1.50 0.5571
Comparison in Aquaporin-4 for Prostati and Aortic 442
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Aortic 10 165.4 344.57 523 .75 172 .28 250 .47 457 .26 79. 206
Aqua Prostati 10 238.33 413.84 589 .35 168 .7S 245 .35 447 .92 77. 587
Aqua Diff (1-2) -302.2 -69.27 163 .67 187 .34 247 .93 366 .64 110 .88 T-Tests
Variable Method Variances DF t Value Pr > |t|
Aqua Pooled Equal 18 -0 62 0.5400
Aqua Satterthwaite Unequal 18 -0.S2 0.S400
Equality of Variances
Variable Method Num DF Den DF P Value Pr > F Aqua Folded F 9 9 1.04 0.9519
Comparison in Aquaponn-4 for Prostati and Parkmso 443
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Parkmso 10 85.402 88.731 92.061 3.2016 4.6546 8.4974 1.4719 Aqua Prostati 10 238.33 413.84 589.35 168.76 245.35 447.92 77.587 Aqua Dlff (1-2) -488.1 -325.1 -162.1 131.12 173.52 256.61 77.601
T-Tests Variable Method Variances DF t Value Pr > | t |
Aqua Pooled Equal 18 -4.19 0.0006
Aqua Satterthwaite Unequal 9.01 -4.19 0.0023
Equality of Variances
Variable Method Hum DF Den DF F Value Pr > F Aqua Folded F 9 9 2778.58 -=.0001
Comparison in Aquapoπn-4 for Arthπti and Aortic 444
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Aortic 10 165.4 344.57 523.75 172.28 250.47 457.26 79.206 Aqua Arthritl 10 363.49 506.92 650.35 137.91 200.5 366.04 63.404 Aqua Dlff (1-2) -375.5 -162.3 50.809 171.42 226.87 335.5 101.46
T-Tests Variable Method Variances DF t Value Pr > \t\
Aqua Pooled Equal 18 -1.60 0.1270
Aqua Satterthwaite Unequal 17.2 -1.60 0.1278
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F Aqua Folded F 9 9 1.56 0.5178
Comparison m Aquaporm-4 for Arthπti and Parkmso 445
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N N M Meeaann M Meeaann Mean Std Dev Std Dev Std Dev Std Err
Aqua Arthriti 10 363.49 506 .92 650.35 137 .91 200.5 366 .04 63 .404 Aqua Parkmso 10 85.402 88. 731 92.061 3.2016 4.6546 8.4974 1. 4719 Aqua Diff (1-2) 284.94 418 .19 551.43 107 .16 141.81 209 .72 63 .421 T-Tests
Variable Method Variances DF t Value Pr > |t|
Aqua Pooled Equal 18 6.59 <.0001 Aqua Satterthwaite Unequal 9.01 6.59 <.0001
Equality of Variances
Variable Method Num DF Den DF F Value Pr > F
Aqua Folded F 9 9 1855.55 <.0001
Comparison in Aquaporm-4 for Aortic and Parkmso 446
The TTEST Procedure Statistics
Lower CL Upper CL Lower CL Upper CL
Variable Disease N Mean Mean Mean Std Dev Std Dev Std Dev Std Err
Aqua Aortic 10 165.4 344 .57 523 .75 172.28 250.47 457.26 79.206
Aqua Parkmso 10 85.402 88. 731 92.061 3.2016 4.6546 8.4974 1.4719
Aqua Diff (1-2) 89.406 255 84 422 .28 133.85 177.14 261.96 79.22
T-Tests
Variable Method Variances DF t Value Pr > |t|
Aqua Pooled Equal 18 3.23 0.0047 Aqua Satterthwaite Unequal 9.01 3.23 0.0103
Equality of Variances
Variable Method Num DF Den DF F Value Pr > P Aqua Folded F 9 9 2895.75 <.0001
It is understood that the disclosed method and compositions are not limited to the particular methodology, protocols, and reagents described as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims.
It must be noted that as used herein and in the appended claims, the singular forms "a ", "an", and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, reference to "a calcifying nano-particle" includes a plurality of such calcifying nano-particles, reference to "the calcifying nano-particle" is a reference to one or more calcifying nano-particles and equivalents thereof known to those skilled in the art, and so forth.
"Optional" or "optionally" means that the subsequently described event, circumstance, or material may or may not occur or be present, and that the description includes instances where the event, circumstance, or material occurs or is present and instances where it does not occur or is not present.
Ranges may be expressed herein as from "about" one particular value, and/or to "about" another particular value. When such a range is expressed, also specifically contemplated and considered disclosed is the range from the one particular value and/or to the other particular value unless the context specifically indicates otherwise. Similarly, when values are expressed as approximations, by use of the antecedent "about," it will be understood that the particular value forms another, specifically contemplated embodiment that should be considered disclosed unless the context specifically indicates otherwise. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint unless the context specifically indicates otherwise. Finally, it should be understood that all of the individual values and sub-ranges of yalues contained within an explicitly disclosed range are also specifically contemplated and should be considered disclosed unless the context specifically indicates otherwise. The foregoing applies regardless of whether in particular cases some or all of these embodiments are explicitly disclosed. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of skill in the art to which the disclosed method and compositions belong. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present method and compositions, the particularly useful methods, devices, and materials are as' described. Publications cited herein and the material for which they are cited are hereby specifically incorporated by reference. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such disclosure by virtue of prior invention. No admission is made that any reference constitutes prior art. The discussion of references states what their authors assert, and applicants reserve the right to challenge the accuracy and pertinency of the cited documents. It will be clearly understood that, although a number of publications are referred to herein, such reference does not constitute an admission that any of these documents forms part of the common general knowledge in the art.
Throughout the description and claims of this specification, the word "comprise" and variations of the word, such as "comprising" and "comprises," means "including but not limited to," and is not intended to exclude, for example, other additives, components, integers or steps. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the method and compositions described herein. Such equivalents are intended to be encompassed by the following claims.

Claims

CLAIMSWe claim: '
1. A method for detecting calcifying nano-particles, the method comprising detecting calcifying nano-particles by detecting one or more proteins or components on the calcifying nano-particle.
2. The method of claim 1, wherein the calcifying nano-particles are detected by detecting one or more of the proteins selected from the group consisting of the proteins anti- Fetuin A, calmodulin, Tgase II, MMP-9, MMP-3, CD 42b, NF-kappa B5 osteopontin, Factor X/Xa, CD 14, prothrombine, Factor DC, Fetuin B, CD40, anti-myeloperoxidase, Fibronectin, Factor VII, tissue factor, human complement 5b-9, human CRP, matrix GLA5 CD61, Kappa Light Chain, Macrophage, factor XIIIA, hsp 60, fibrillin- 1, B2 micro gl, CD 18, laminin, trypsin, Notch-1, BSA, LBP, PTX3, complement C5, fibrinogen, D-Dimer, factor V, human gamma-Gla, TF-VIIa, complement C3c, Complement C4, antichymotrypsin, Annexin V, Lipid A, isopeptide bond, vitronectin, thrombin, osteocalcin, Troponin T, vimentin, tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, kallikrein, Prothr Fl, goat- ATIII, Thrombin, Factor VIII, heparan Sulph, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c- Jun, TGase3, alpha fetoprotein, PSA, erbB2, VEGF, alpha synuclein, mucin-1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Osteonectin, RAGE, PGRP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C, Macrophage Scavenger Receptor Type I, anti-Thrombin, Protein S, BAFF on the calcifying nano-particle.
3. The method of claim 1, wherein the calcifying nano-particles are detected by detecting two or more proteins or components on the calcifying nano-particle.
4. The method of claim 1, wherein the calcifying nano-particles are detected by detecting one or more proteins or components with a GLA-containing domain.
5. The method of claim 1, wherein the calcifying nano-particles are detected by detecting one or more proteins or components with a calcium binding domain.
6. The method of claim 1, wherein the calcifying nano-particle is captured, identified, or both prior to, simultaneous with, or following detection of one or more of the proteins or components.
7. The method of claim 6, wherein capture or identification of the calcifying nano- particle indicates that the detected proteins or components are on the calcifying nano-particle.
8. The method of claim 6, wherein the calcifying nano-particle is captured by binding at least one compound to one or more of the proteins or components, wherein the compound is or becomes immobilized.
9. The method of claim 6, wherein the calcifying nano-particle is identified by binding at least one compound to one or more of the proteins or components, wherein the calcifying nano-particle is separated based on the compound.
10. The method of claim 9, wherein the calcifying nano-particle is separated by fluorescence activated sorting.
11. The method of claim 1 , wherein one or more of the proteins are detected by binding at least one compound to the protein and detecting the bound compound.
12. The method of claim 11, wherein detection of two or more bound compounds indicates that the proteins to which the compounds are bound are on the calcifying nano- particle.
13. The method of claim 12, wherein the two or more compounds are detected in the same location or at the same time.
14. The method of claim 11, wherein at least one of the compounds is an antibody, wherein the antibody is specific for the protein.
15. The method of claim 1, wherein the calcifying nano-particles comprise calcium phosphate and one or more of the proteins.
16. The method of claim 1, wherein the proteins are detected by detecting any combination of 100 or fewer of the proteins selected from the group consisting of proteins with a GLA-containing domain, clotting factor V, clotting factor VII, clotting factor IX, clotting factor X, tissue factor-clotting factor Vila complex, fibrin, fibrinogen, factor XIIIa, fragments of factor II, thrombin, prothrombin Fragment 1, matrix GLA-protein and osteocalcin on the calcifying nano-particle.
17. The method of claim 16, wherein the proteins are detected by detecting any combination of 75 or fewer of the proteins.
18. The method of claim 17, wherein the proteins are detected by detecting any combination of 50 or fewer of the proteins.
19. The method of claim 18, wherein the proteins are detected by detecting any combination of 10 or fewer of the proteins.
• 20. The method of claim 16, wherein the combination of proteins is detected in the same assay.
21. The method of claim 16, wherein the combination of proteins is detected simultaneously.
22. The method of claim 16, wherein the combination of proteins is detected on the same calcifying nano-particle.
23. The method of claim 16, wherein the combination of proteins is detected on or within the same device.
24. The method of claim 16, wherein the combination of proteins detected constitutes a pattern of proteins.
25. The method of claim 24, wherein the pattern indicates or identifies a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination.
26. The method of claim 24, wherein the pattern indicates or identifies a treatment to inhibit, remove or prevent the calcifying nano-particles.
27. The method of claim 24, wherein the pattern identifies the type of calcifying nano- particles detected.
28. The method of claim 1, wherein the proteins are detected by detecting the presence or absence of any combination of 10 or fewer of the proteins selected from the group consisting of proteins anti-Fetuin A, calmodulin, Tgase II, MMP-9, MMP-3, CD 42b, NF- kappa B, osteopontin, Factor X/Xa, CD 14, prothrombine, Factor DC, Fetuin B, CD40, anti- myeloperoxidase, Fibronectin, Factor VII, tissue factor, human complement 5b-9, human CRP, matrix GLA, CD61, Kappa Light Chain, Macrophage, factor XIIIA, hsp 60, fibrillin- 1, B2 microgl, CD 18, laminin, trypsin, Notch-1, BSA, LBP, PTX3, complement C5, fibrinogen, D- Dimer, factor V, human gamma-Gla, TF-VIIa, complement C3c, Complement C4, antichymotrypsin, Annexin V, Lipid A, isopeptide bond, vitronectin, thrombin, osteocalcin, Troponin T, vimentin, tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, kallikrein, Prothr Fl, goat- ATIII, Thrombin, Factor VIII, heparan Sulph, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c-Jun, TGase3, alpha fetoprotein, PSA, erbB2, VEGF, alpha synuclein, mucin- 1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Osteonectin, RAGE, PGRP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C, Macrophage Scavenger Receptor Type I, anti-Thrombin, Protein S, BAFF on the calcifying nano-particle.
29. The method of claim 28, wherein the pattern of the presence or absence of the proteins indicates or identifies a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination.
30. The method of claim 28, wherein the pattern of the presence or absence of the proteins indicates or identifies a treatment to inhibit, remove or prevent the calcifying nano- particles.
31. The method of claim 28, wherein the pattern of the presence or absence of the proteins identifies the type of calcifying nano-particles detected.
32. The method of claim 28, wherein the presence of one or more of the proteins indicates or identifies a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination.
33. The method of claim 28, wherein the presence of one or more of the proteins indicates or identifies a treatment to inhibit, remove or prevent the calcifying nano-particles.
34. The method of claim 28, wherein the presence of one or more of the proteins identifies the type of calcifying nano-particles detected.
35. The method of claim 28, wherein the absence of one or more of the proteins indicates or identifies a disease or condition, a risk of a disease or condition, the severity of a disease or condition, or a combination.
36. The method of claim 28, wherein the absence of one or more of the proteins indicates or identifies a treatment to inhibit, remove or prevent the calcifying nano-particles.
37. The method of claim 28, wherein the absence of one or more of the proteins identifies the type of calcifying nano-particles detected.
38. The method of claim 1, wherein at least one of the proteins is detected using a microarray, coded beads, coated beads, flow cytometry, ELISA, mass spectrometry, fluorescence, chemiluminescence, spectrophotometry, chromatography, electrophoresis, or a combination.
39. The method of claim 1, wherein the proteins on the calcifying nano-particle are detected by
(a) capturing the calcifying nano-particle,
(b) binding a detection compound to one or more of the proteins or components of said particle, and
(c) detecting the detection compound.
40. The method of 39, wherein the calcifying nano-particle is captured by binding a capture compound to one or more of the proteins or components of said particle, wherein the capture compound is or becomes immobilized.
41. The method of claim 40, wherein the proteins to which capture compounds bind mediate capture, wherein the detection compound is bound to one of the proteins or components of said particle, wherein the calcifying nano-particle is characterized by determining which proteins mediate capture of the calcifying nano-particle to which the detected detection compound is bound.
42. The method of claim 40, wherein the capture compound is bound to one of the proteins or components of said particle, wherein the detection compounds detected indicate which of the proteins is present on the calcifying nano-particle, wherein the calcifying nano- particle is characterized by which proteins are present on the calcifying nano-particle.
43. The method of claim 1, wherein the proteins on the calcifying nano-particle are detected by
(a) binding a detection compound to one or more of the proteins,
(b) capturing the calcifying nano-particle, and
(c) detecting the detection compound.
44. A method for detecting one or more proteins, the method comprising detecting one or more proteins on a calcifying nano-particle.
45. The method of claim 44, wherein the proteins are selected from the group consisting of proteins anti-Fetuin A, calmodulin, Tgase II, MMP-9, MMP-3, CD 42b, NF- kappa B, osteopontin, Factor X/Xa, CD 14, prothrombine, Factor DC, Fetuin B, CD40, anti- myeloperoxidase, Fibronectin, Factor VII, tissue factor, human complement 5b-9, human CRP, matrix GLA, CD61, Kappa Light Chain, Macrophage, factor XIIIA, hsp 60, fibrillin- 1, B2 microgl, CD 18, laminin, trypsin, Notch-1, BSA, LBP, PTX3, complement C5, fibrinogen, D- Dimer, factor V, human gamma-Gla, TF-VIIa, complement C3c, Complement C4, antichymotrypsin, Annexin V, Lipid A, isopeptide bond, vitronectin, thrombin, osteocalcin, Troponin T, vimentin, tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, kallikrein, Prothr Fl, goat- ATIII, Thrombin, Factor VIII, heparan Sulph, Factor XI, c-jun, Fra-2, Fra-1, JunB, P-c-Jun, TGase3, alpha fetoprotein, PSA, erbB2, VEGF, alpha synuclein, mucin- 1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Osteonectin, RAGE, PGRP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C, Macrophage Scavenger Receptor Type I, anti-Thrombin, Protein S, BAFF on the calcifying nano-particle.
46. The method of claim 44, wherein two or more proteins are detected on the calcifying nano-particle.
47. The method of claim 44, wherein one or more of the proteins are detected by binding at least one compound to the protein and detecting the bound compound.
48. The method of claim 47, wherein at least one of the compounds is an antibody, wherein the antibody is specific for the protein.
49. The method of claim 44, wherein the calcifying nano-particles comprise calcium phosphate and one or more of the proteins.
50. A method of characterizing a calcifying nano-particle, the method comprising identifying one or more proteins on a calcifying nano-particle.
51. The method of claim 50, wherein the proteins are selected from the group consisting of proteins anti-Fetuin A, calmodulin, Tgase II, MMP-9, MMP-3, CD 42b, NF- kappa B, osteopontin, Factor XIXa, CD14, prothrombine, Factor IX, Fetuin B, CD40, anti- myeloperoxidase, Fibronectin, Factor VII, tissue factor, human complement 5b-9, human CRP, matrix GLA, CD61, Kappa Light Chain, Macrophage, factor XIIIA, hsp 60, fibrillin- 1, B2 microgl, CD 18, larninin, trypsin, Notch-1, BSA, LBP, PTX3, complement C5, fibrinogen, D- Dimer, factor V, human gamma-Gla, TF-VIIa, complement C3c, Complement C4, antichymotrypsin, Annexin V, Lipid A, isopeptide bond, vitronectin, thrombin, osteocalcin, Troponin T, vimentin, tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, kallikrein, Prothr Fl, goat- ATIII, Thrombin, Factor VIII5 heparan Sulph, Factor XI, c-jun, Fra-2, Fra-1, JunB, P-c-Jun, TGase3, alpha fetoprotein, PSA, erbB2, VEGF, alpha synuclein, mucin-1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Osteonectin, RAGE, PGRP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C, Macrophage Scavenger Receptor Type I, anti-Thrombin, Protein S, BAFF on the calcifying nano-particle.
52. The method of claim 50, wherein the calcifying nano-particles are characterized by identifying two or more proteins on the calcifying nano-particle.
53. The method of claim 50, wherein the identified proteins identify the type of calcifying nano-particle.
54. The method of claim 53, wherein the identified type of calcifying nano-particle is related to or associated with a disease or condition.
55. The method of claim 50, wherein the identified proteins identify a disease or condition with which calcifying nano-particles having the identified proteins are related or associated.
56. The method of claim 50, wherein one or more of the proteins are identified by binding at least one compound to the proteins or components of said particle and detecting the bound compound.
57. The method of claim 56, wherein at least one of the compounds is an antibody, wherein the antibody is specific for the proteins or components of said particle.
58. The method of claim 50, wherein the calcifying nano-particles comprise calcium phosphate and one or more of the proteins or components of said particle.
59. A method of diagnosing a disease or condition, the method comprising identifying one or more proteins or components on a calcifying nano-particle from a subject, wherein the identified proteins identify a disease or condition with which calcifying nano-particles having the identified proteins are related or associated.
60. The method of claim 59, wherein the proteins are selected from the group consisting of proteins anti-Fetuin A, calmodulin, Tgase II, MMP-9, MMP-3, CD 42b, NF- kappa B, osteopontin, Factor X/Xa, CD 14, prothrombine, Factor DC, Fetuin B, CD40, anti- myeloperoxidase, Fibronectin, Factor VII, tissue factor, human complement 5b-9, human CRP, matrix GLA, CD61, Kappa Light Chain, Macrophage, factor XIIIA, hsp 60, fibrillin- 1, B2 microgl, CD 18, laminin, trypsin, Notch-1, BSA, LBP, PTX3, complement C5, fibrinogen, D- Dimer, factor V, human gamma-Gla, TF-VIIa, complement C3c, Complement C4, antichymotrypsin, Annexin V, Lipid A, isopeptide bond, vitronectin, thrombin, osteocalcin, Troponin T, vimentin, tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, kallikrein, Prothr Fl, goat- ATIII, Thrombin, Factor VIII, heparan Sulph, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c-Jun, TGase3, alpha fetoprotein, PSA, erbB2, VEGF, alpha synuclein, mucin-1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Osteonectin, RAGE, PGRP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C, Macrophage Scavenger Receptor Type I, anti-Thrombin, Protein S, BAFF on the calcifying nano-particle.
61. The method of claim 59, wherein the disease or condition is diagnosed by identifying two or more proteins or components on the calcifying nano-particle.
62. The method of claim 59, wherein the identified proteins identify a disease or condition that is caused by calcifying nano-particles having the identified proteins or components of said particle.
63. The method of claim 59, wherein the identified proteins identify a disease or condition in which calcifying nano-particles having the identified proteins or components of said particle are produced.
64. The method of claim 59, wherein one or more of the proteins are identified by binding at least one compound to the proteins or components of said particle and detecting the bound proteins or components therein.
65. The method of claim 64, wherein at least one of the compounds is an antibody, wherein the antibody is specific for the protein.
66. The method of claim 59, wherein the calcifying nano-particles comprise calcium phosphate and one or more of the proteins or components of said particle.
67. A method of assessing the prognosis of a disease or condition, the method comprising identifying one or more proteins or components on a calcifying nano-particle from a subject, wherein the identified proteins identify calcifying nano-particles that are related to or associated with the prognosis of the disease or condition.
68. The method of claim 67, wherein the proteins are selected from the group consisting of proteins anti-Fetuin A, calmodulin, Tgase II, MMP-9, MMP-3, CD 42b, NF- kappa B, osteopontin, Factor X/Xa, CD 14, prothrombine, Factor IX, Fetuin B, CD40, anti- myeloperoxidase, Fibronectin, Factor VII, tissue factor, human complement 5b-9, human CRP, matrix GLA, CD61, Kappa Light Chain, Macrophage, factor XIIIA, hsp 60, fibrillm-l, B2 microgl, CD 18, laminin, trypsin, Notch-1, BSA, LBP, PTX3, complement C5, fibrinogen, D- Dimer, factor V, human gamma-Gla, TF-VIIa, complement C3c, Complement C4, antichymotrypsin, Annexin V, Lipid A, isopeptide bond, vitronectin, thrombin, osteocalcin, Troponin T, vimentin, tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, kallikrein, Prothr Fl, goat- ATIII, Thrombin, Factor VIII, heparan Sulph, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c-Jun, TGase3, alpha fetoprotein, PSA, erbB2, VEGF, alpha synuclein, mucin-1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Osteonectin, RAGE, PGRP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C, Macrophage Scavenger Receptor Type I, anti-Thrombin, Protein S5 BAFF on the calcifying nano-particle.
69. The method of claim 67, wherein the prognosis of a disease or condition is assessed by identifying two or more proteins or components on the calcifying nano-particle.
70. The method of claim 67, wherein one or more of the proteins or components of said particle are identified by binding at least one compound to said proteins or components and detecting the bound compound.
71. The method of claim 70, wherein at least one of the compounds is an antibody, wherein the antibody is specific for the proteins or components of said particle.
72. The method of claim 67, wherein the calcifying nano-particles comprise calcium phosphate and one or more of the proteins or components of said particle.
73. A method of identifying a subject at risk of a disease or condition, the method comprising identifying one or more proteins or components on a calcifying nano-particle from a subject, wherein the identified proteins or components identify calcifying nano-particles that are related to or associated with a risk of developing a disease or condition.
74. The method of claim 73, wherein the proteins are selected from the group consisting of proteins anti-Fetuin A, calmodulin, Tgase II, MMP-9, MMP-3, CD 42b, NF- kappa B, osteopontin, Factor XfXa, CD 14, prothrombine, Factor IX, Fetuin B, CD40, anti- myeloperoxidase, Fibronectin, Factor VII, tissue factor, human complement 5b-9, human CRP, matrix GLA, CD61, Kappa Light Chain, Macrophage, factor XIIIA, hsp 60, fibrillin- 1, B2 microgl, CD 18, laminin, trypsin, Notch-1, BSA, LBP, PTX3, complement C5, fibrinogen, D- Dimer, factor V, human gamma-Gla, TF-VIIa, complement C3c, Complement C4, antichymotrypsin, Annexin V, Lipid A, isopeptide bond, vitronectin, thrombin, osteocalcin, Troponin T, vimentin, tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, kallikrein, Prothr Fl, goat- ATIII, Thrombin, Factor VIII, heparan Sulph, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c-Jun, TGase3, alpha fetoprotein, PSA, erbB2, VEGF, alpha synuclein, mucin-1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Osteonectin, RAGE, PGRP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C, Macrophage Scavenger Receptor Type I, anti-Thrombin, Protein S, BAFF on the calcifying nano-particle.
75. The method of claim 73, wherein the subject is identified by identifying two or more proteins on the calcifying nano-particle.
76. The method of claim 73, wherein one or more of the proteins or components are identified by binding at least one compound to the proteins or component and detecting the bound compound.
77. The method of claim 76, wherein at least one of the compounds is an antibody, wherein the antibody is specific for the protein or component.
78. The method of claim 73, wherein the calcifying nano-particles comprise calcium phosphate and one or more of the protein or components of said particle.
79. An isolated calcifying nano-particle, wherein the calcifying nano-particle comprises one or more of the proteins selected from the group consisting of proteins anti- Fetuin A, calmodulin, Tgase II, MMP-9, MMP-3, CD 42b, NF-kappa B, osteopontin, Factor X/Xa, CD 14, prothrombine, Factor DC, Fetuin B, CD40, anti-myeloperoxidase, Fibronectin, Factor VII, tissue factor, human complement 5b-9, human CRP, matrix GLA, CD61, Kappa Light Chain, Macrophage, factor XIIIA, hsp 60, fibrillin- 1, B2 microgl, CD 18, laminin, trypsin, Notch- 1, BSA, LBP, PTX3, complement C5, fibrinogen, D-Dimer, factor V, human gamma-Gla, TF-VIIa, complement C3c, Complement C4, antichymotrypsin, Annexin V, Lipid A, isopeptide bond, vitronectin, thrombin, osteocalcin, Troponin T, vimentin, tropomyosin, HAS, Troponin I cardiac, Apo Al, MHC class I, Amyloid P protein, sCD40 L, kallikrein, Prothr Fl, goat- ATIII, Thrombin, Factor VIII, heparan Sulph, Factor XI, c-jun, Fra-2, Fra-1, Jun B, P-c- Jun, TGase3, alpha fetoprotein, PSA, erbB2, VEGF, alpha synuclein, mucin- 1, Cystatin A, Cystatin S, Prostein, Aquaporin 4, Trypsin, Osteonectin, RAGE, PGRP-I Beeta, PGRP-S, Gram positive bacteria, Troponin C Cardiac, Protein C, Macrophage Scavenger Receptor Type I, anti-Thrombin, Protein S, BAFF on the calcifying nano-particle.
80. A composition comprising a calcifying nano-particle and one or more compounds bound to one or more proteins or components on the calcifying nano-particle.
81. The composition of claim 80, wherein the composition comprises a calcifying nano-particle and one or more compounds bound to two or more proteins or components on the calcifying nano-particle.
82. The composition of claim 80, wherein at least one of the compounds is an antibody, wherein the antibody is specific for the protein or components.
83. The composition of claim 80, wherein the calcifying nano-particles comprise calcium phosphate and one or more of the proteins or components.
84. The composition of claim 80, wherein at least one of the compounds blocks the calcifying nano-particle.
85. A method of detecting a particle wherein proteins on the particle are detected by (a) capturing the particle, (b) binding a detection compound to one or more of the proteins or components of said particle, and
(c) detecting the detection compound.
86. The method of claim 85, wherein said particle is a stable particle, such as a microparticle, virus, spore, bacteria, prion, mineral, metal, or synthetic particle as introduced into the circulation of an animal.
87. The method of claim 85 wherein said proteins or compounds are quantitated using a single standard curve.
88. The method of claim 87, wherein said curve is created by including, as the standard, at least one protein or other component of said particle as a standard for the assay
89. The method of claim 87, wherein said curve is created by including various concentrations of CNPs or at least one of the CNP antigen into the assay format.
90. The method of claim 1, wherein said proteins or components may be any of those that adhere to the surface of said particle.
91. The method of claim 1 , wherein said proteins may be any calcium binding protein.
92. The method of claim 1, wherein said proteins may be any proteins that bind to calcium binding proteins.
93. The method of claim 39, wherein said detector antibody is directed against conformationally changed or chemically modified epitope.
94. The method of claim 39, wherein said proteins or compounds are quantitated using a single standard curve.
95. The method of claim 39, wherein said curve is created by including various concentrations of CNPs or at least one of the CNP antigen into the assay format.
96. The method of claim 39, wherein said proteins or components may be any of those that adhere to the surface of said particle.
97. The method of claim 39, wherein said proteins may be any calcium binding protein.
98. The method of claim 39, wherein said proteins may be any proteins that bind to calcium binding proteins.
99. A kit comprising one or more detection compounds, one or more capture compounds, and one or more solid supports for the detection of calcifying nanoparticles and assessment or quantification of the proteins or components associated thereupon.
100. The method of claim 59, wherein said pattern of said proteins indicate or identify a disease or condition, or a combination of said diseases or conditions including but not limited to heart or circulatory diseases such as Arteriosclerosis, Atherosclerosis, Coronary Heart Disease, Chronic Heart Failure, Valve Calcifications, Arterial Aneurysms, Calcific Aortic Stenosis, Transient Cerebral Ischemia, Stroke, Peripheral Vascular Disease, Monckeberg's Disease, Vascular Thrombosis; Dental Diseases such as Dental Plaque, Gum Disease (dental pulp stones), calcification of the dentinal papilla, and Salivary Gland Stones; Chronic Infection Syndromes such as Chronic Fatigue Syndrome; Kidney and Bladder Stones, Gall Stones, Pancreas and Bowel Diseases such as Pancreatic Duct Stones, Crohn's Disease, Colitis Ulcerosa; Blood disorders; Adrenal Calcification; Liver Diseases such as Liver Cirrhosis and Liver Cysts; Testicular Microliths, Chronic Calculous Prostatitis, Prostate Calcification, Calcification in Hemodialysis Patients, Malacoplakia; Autoimmune Diseases such as Lupus Erythematosous, Scleroderma, Dermatomyositis, Cutaneous polyarteritis, Panniculitis (Septal and Lobular), Antiphospholipid Syndrome, Arteritis Nodosa, Thrombocytopenia, Hemolytic Anemia, Myelitis, Livedo Reticularis, Chorea, Migraine, Junvenile Dermatomyositis, Graves Disease, Chronic Thyroiditis, Hypothyreoidism, Type 1 Diabetes Mellitis, Addison's Disease, and Hypopituitarism; Placental and Fetal Disorders, Polycystic Kidney Disease, Glomerulopathies; Eye Diseases such as Corneal Calcifications, Cataracts, Macular Degeneration and Retinal Vasculature-derived Processes and other Retinal Degenerations; Retinal Nerve Degeneration, Retinitis, and Iritis; Ear Diseases such as Otosclerosis, Degeneration of Otoliths and Symptoms from the Vestibular Organ and Inner Ear (Vertigo and Tinnitus); Thyroglossal cysts, Thyroid Cysts, Ovarian Cysts; Cancer such as Meningiomas, Breast Cancer, Prostate Cancer, Thyroid Cancer, Serous Ovarian Adenocarcinoma; Skin diseases such as Calcinosis Cutis, Skin Stones, Calciphylaxis, Psoriasis, Eczema, Lichen Ruber Planus or Lichen Simple Cysts;, Choroid Plexus Calcification, Neuronal Calcification, Calcification of the FaIx Cerebri, Calcification of the Intervertebral Cartilage or Disc, Mercranial or Cerebral Calcification, Rheumatoid Arthritis, Calcific Tenditis, Oseoarthritis, Fibromyalgia, Bone Spurs, Diffuse Interstitial Skeletal Hyperostosis, Intracranial Calcifications such as Degenerative Disease Processes and Dementia; Erythrocyte-Related Diseases involving Anemia, Intraerythrocytic Nanobacterial Infection and Splenci Calcifications; Chronic Obstructive Pulmonary Disease, Broncholiths, Bronchial Stones, Neuropathy, Calcifications and Encrustations of Implants, Mixed Calcified Biofilms, and Myelodegenerative Disorders such as Multiple Sclerosis, Lou Gehrig's, and Alzheimer's Disease.
101. The method of claim 67, wherein said pattern of said proteins indicate prognosis of a disease or condition including, but not limited to heart or circulatory diseases such as Arteriosclerosis, Atherosclerosis, Coronary Heart Disease, Chronic Heart Failure, Valve Calcifications, Arterial Aneurysms, Calcific Aortic Stenosis, Transient Cerebral Ischemia, Stroke, Peripheral Vascular Disease, Monckeberg's Disease, Vascular Thrombosis; Dental Diseases such as Dental Plaque, Gum Disease (dental pulp stones), calcification of the dentinal papilla, and Salivary Gland Stones; Chronic Infection Syndromes such as Chronic Fatigue Syndrome; Kidney and Bladder Stones, Gall Stones, Pancreas and Bowel Diseases such as Pancreatic Duct Stones, Crohn's Disease, Colitis Ulcerosa; Blood disorders; Adrenal Calcification; Liver Diseases such as Liver Cirrhosis and Liver Cysts; Testicular Microliths, Chronic Calculous Prostatitis, Prostate Calcification, Calcification in Hemodialysis Patients, Malacoplakia; Autoimmune Diseases such as Lupus Erythematosous, Scleroderma, Dermatomyositis, Cutaneous polyarteritis, Panniculitis (Septal and Lobular), Antiphospholipid Syndrome, Arteritis Nodosa, Thrombocytopenia, Hemolytic Anemia, Myelitis, Livedo Reticularis, Chorea, Migraine, Junvenile Dermatomyositis, Graves Disease, Chronic Thyroiditis, Hypothyreoidism, Type 1 Diabetes Mellitis, Addison's Disease, and Hypopituitarism; Placental and Fetal Disorders, Polycystic Kidney Disease, Glomerulopathies; Eye Diseases such as Corneal Calcifications, Cataracts, Macular Degeneration and Retinal Vasculature-derived Processes and other Retinal Degenerations; Retinal Nerve Degeneration, Retinitis, and Iritis; Ear Diseases such as Otosclerosis, Degeneration of Otoliths and Symptoms from the Vestibular Organ and Inner Ear (Vertigo and Tinnitus); Thyroglossal cysts, Thyroid Cysts, Ovarian Cysts; Cancer such as Meningiomas, Breast Cancer, Prostate Cancer, Thyroid Cancer, Serous Ovarian Adenocarcinoma; Skin diseases such as Calcinosis Cutis, Skin Stones, Calciphylaxis, Psoriasis, Eczema, Lichen Ruber Planus or Lichen Simple Cysts;, Choroid Plexus Calcification, Neuronal Calcification, Calcification of the FaIx Cerebri, Calcification of the Intervertebral Cartilage or Disc, Intercranial or Cerebral Calcification, Rheumatoid Arthritis, Calcific Tenditis, Oseoarthritis, Fibromyalgia, Bone Spurs, Diffuse Interstitial Skeletal Hyperostosis, Intracranial Calcifications such as Degenerative Disease Processes and Dementia; Erythrocyte-Related Diseases involving Anemia, Intraerythrocytic Nanobacterial Infection and Splenci Calcifications; Chronic Obstructive Pulmonary Disease, Broncholiths, Bronchial Stones, Neuropathy, Calcifications and Encrustations of Implants, Mixed Calcified Biofilms, and Myelodegenerative Disorders such as Multiple Sclerosis, Lou Gehrig's, and Alzheimer's Disease.
102. The method of claim 73, wherein said pattern of said proteins indicates risk of a disease or condition, or combination of diseases or conditions, including but not limited to heart or circulatory diseases such as Arteriosclerosis, Atherosclerosis, Coronary Heart Disease, Chronic Heart Failure, Valve Calcifications, Arterial Aneurysms, Calcific Aortic Stenosis, Transient Cerebral Ischemia, Stroke, Peripheral Vascular Disease, Monckeberg's Disease, Vascular Thrombosis; Dental Diseases such as Dental Plaque, Gum Disease (dental pulp stones), calcification of the dentinal papilla, and Salivary Gland Stones; Chronic Infection Syndromes such as Chronic Fatigue Syndrome; Kidney and Bladder Stones, Gall Stones, Pancreas and Bowel Diseases such as Pancreatic Duct Stones, Crohn's Disease, Colitis Ulcerosa; Blood disorders; Adrenal Calcification; Liver Diseases such as Liver Cirrhosis and Liver Cysts; Testicular Microliths, Chronic Calculous Prostatitis, Prostate Calcification, Calcification in Hemodialysis Patients, Malacoplakia; Autoimmune Diseases such as Lupus Erythematosous, Schleroderma, Dermatomyositis, Cutaneous polyarteritis, Panniculitis (Septal and Lobular), Antiphospholipid Syndrome, Arteritis Nodosa, Thrombocytopenia, Hemolytic Anemia, Myelitis, Livedo Reticularis, Chorea, Migraine, Junvenile Dermatomyositis, Graves Disease, Chronic Thyroiditis, Hypothyroidism, Type 1 Diabetes Mellitis, Addison's Disease, and Hypopituitarism; Placental and Fetal Disorders, Polycystic Kidney Disease, Glomerulopathies; Eye Diseases such as Corneal Calcifications, Cataracts, Macular Degeneration and Retinal Vasculature-derived Processes and other Retinal Degenerations; Retinal Nerve Degeneration, Retinitis, and Iritis; Ear Diseases such as Otosclerosis, Degeneration of Otoliths and Symptoms from the Vestibular Organ and Inner Ear (Vertigo and Tinnitus); Thyroglossal cysts, Thyroid Cysts, Ovarian Cysts; Cancer such as Meningiomas, Breast Cancer, Prostate Cancer, Thyroid Cancer, Serous Ovarian Adenocarcinoma; Skin diseases such as Calcinosis Cutis, Skin Stones, Calciphylaxis, Psoriasis, Eczema, Lichen Ruber Planus or Lichen Simple Cysts;, Choroid Plexus Calcification, Neuronal Calcification, Calcification of the FaIx Cerebri, Calcification of the Intervertebral Cartilage or Disc, Intercranial or Cerebral Calcification, Rheumatoid Arthritis, Calcific Tenditis, Oseoarthritis, Fibromyalgia, Bone Spurs, Diffuse Interstitial Skeletal Hyperostosis, Intracranial Calcifications such as Degenerative Disease Processes and Dementia; Erythrocyte-Related Diseases involving Anemia, Intraerythrocytic Nanobacterial Infection and Splenci Calcifications; Chronic Obstructive Pulmonary Disease, Broncholiths, Bronchial Stones, Neuropathy, Calcifications and Encrustations of Implants, Mixed Calcified Biofϊlms, and Myelodegenerative Disorders such as Multiple Sclerosis, Lou Gehrig's, and Alzheimer's Disease.
103. A method of identifying a treatment to inhibit, remove or prevent the calcifying nano-particles or monitor response to said treatment, the method comprising identifying one or more proteins or components on a calcifying nano-particle from a subject, wherein the identified proteins are related to or associated with the selection of therapy or for predicting response to treatment.
104. A method for detecting calcifying nanoparticles on or in foreign devices implanted or to be implanted, or introduced into body cavities including, but not limited to stents, scopes, tubes, endoscopes, catheters, pumps, pace makers, dental appliances, and other implants by detecting one ore more proteins or components on the calcifying nano-particle.
105. A method for detecting calcifying nano-particles in biological materials or donors thereof including, but not limited to blood, tissues, organs, cells, and biopharmaceutical products by detecting one ore more proteins or components on the calcifying nano-particle.
106. A method for detecting calcifying nano-particles in biological materials or donors thereof including but not limited to dairy products, meats, water, and other food stuffs by detecting one or more proteins or components on the calcifying nano-particle.
107. A method for determining risk of future severe adverse health events for individuals to be placed in extreme, demanding, or solitary environments including, but not limited to astronauts, military personnel, and explorers or for aiding in the determination of insurance risk by detecting one ore more proteins or components, or patterns thereof, on the calcifying nano-particle.
PCT/US2005/044589 2005-12-09 2005-12-09 Detection of calcifying nano-particles, and associated proteins thereon Ceased WO2007070021A1 (en)

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