WO2008038149A2 - Process for production of cytidine 5'-monophosphate - Google Patents

Abstract

Disclosed is a protein having an activity of producing cytidine 5'-monophosphate (CMP) from cytosine. Specifically disclosed is: a protein having an amino acid sequence depicted in SEQ ID NO:1, 2 or 30; or a protein which has an amino acid sequence having the substitution of at least one amino acid residue selected from amino acid residues at the 36th, 46th, 94th, 102nd, 121st, 141st, 143rd, 167th and 198th positions in an amino acid sequence depicted in SEQ ID NO:1, 2 or 30 by a different amino acid residue.

Description

 [Document Name] Statement

 Patent application title: Method for producing cytidine 5, monomonophosphate

 【Technical field】

 [0001]

 The present invention relates to a method for producing a novel protein having an activity of producing cytidine 5, monomonophosphate (CMP) from cytosine, the protein, a DNA encoding the protein, a recombinant DNA containing the DNA, the assembly The present invention relates to a microorganism having a recombinant DNA, and a method for producing CMP using a culture of the microorganism.

 [Background]

 [0002]

 CMP is used with other nucleotides, adenosine 5'-monophosphate (AMP), guanosine 5'-monophosphate (GMP), and uridine 5'-monophosphate (UMP) as an additive to infant milk. Conventionally, CMP has been produced by enzymatic degradation of yeast RNA (Non-patent Document 1). However, this RNA degradation method has the disadvantage that four nucleotides are produced at the same time, resulting in a surplus in the product due to the difference between production and demand. For this reason, development of an inexpensive method for producing individual nucleotides is desired.

 [0003]

 Among the four types of nucleotides described above, an industrial individual production method has been established that can replace the RNA degradation method for GMP (Patent Document 1). On the other hand, inexpensive individual manufacturing methods for CMP, A MP, and UMP have not yet been established. As an individual method for producing these nucleotides, there is a method using a salvage synthesis route and using the corresponding base produced by the chemical synthesis method as a substrate. As a specific example using this route, adenosine with adenine as a substrate 5 '— An industrial production method of triphosphoric acid (ATP) is mentioned (Patent Document 2).

 0004

 Enzymes involved in the salvage synthesis pathway include nucleotides corresponding to bases such as uracil phosphoribosyltransferase (UPRTase), which catalyzes the reaction of UMP and pyrophosphate from uracil and phosphoribosylpyrophosphate (PRPP). Enzymes that produce in one step are known. However, the enzymes of the salvage synthesis pathway that produce CMP are not known across all species.

 [Non-Patent Document 1] J. Gen. Appl. Microbiol., 3, 55 (1957)

 [Patent Document 1] Japanese Patent Laid-Open No. 62-285797

 [Patent Document 2] JP-A-2-134394

DISCLOSURE OF THE INVENTION [Problems to be solved by the invention]

 [0005]

 An object of the present invention is to provide a method for producing a novel protein having an activity of generating CMP from cytosine, the protein, a DNA encoding the protein, a recombinant DNA containing the DNA, and the recombinant DNA. It is an object of the present invention to provide a method for producing CMP using a microorganism and a culture of the microorganism.

 [Means for Solving the Problems]

 [0006]

 The present invention relates to the following (1) to (14).

 (1) A protein having an amino acid sequence represented by SEQ ID NO: 1, 2, or 30, which has an activity of generating cytidine 5′-monophosphate (CMP) from cytosine.

 (2) In the amino acid sequence represented by SEQ ID NO: 1, 2, or 30, one or more amino acid residues selected from the 36th, 94th, 102th, 141st, 143rd and 198th amino acid residues A protein having an amino acid sequence in which an amino acid residue is substituted with another amino acid residue, and having an activity of generating CMP from cytosine.

(3) 36th amino acid residue is cysteine, 94th amino acid residue is tyrosine, 102nd amino acid residue is cysteine, 141st amino acid residue is leucine, 143rd amino acid residue is valine, or The protein according to (2) above, which has an amino acid sequence in which the 198th amino acid residue is substituted with glycine.

 [0007]

 (4) In the amino acid sequence represented by SEQ ID NO: 1, 2, or 30, the 36th, 46th, 94th, 102th, 121st, 141st, 143rd, 167th and 198th amino acids A protein having an amino acid sequence in which one or more amino acid residues selected from residues are substituted with other amino acid residues, and having an activity of generating CMP from cytosine.

 (5) In the amino acid sequence of the protein of any one of (1) to (4) above, amino acids other than the 36th, 94th, 102th, 141st, 143rd, 198th, 201st, 204th and 205th amino acids A protein having an amino acid sequence in which one or more amino acid residues selected from residues are substituted with other amino acid residues, and having an activity of generating CMP from cytosine.

 [0008]

(6) In the amino acid sequence of any one of the proteins (1) to (4) above, the 36th, 46th, 94th, 102th, 121st, 141st, 143rd, 167th, 198th, 201 One or more amino acid residues selected from amino acid residues other than No. 204, No. 205 and No. 205 are replaced with other amino acid residues. A protein having an amino acid sequence and having an activity of generating CMP from cytosine.

 (7) The DNA according to [1] or [2] below.

 [1] DNA encoding any of the proteins (1) to (4) above

 [2] DNA having the base sequence represented by any of SEQ ID NOs: 3 to 5

 (8) A recombinant DNA comprising the DNA of (7) above.

 [0009]

 (9) A microorganism having the recombinant DNA of (8) above.

 (10) The microorganism according to (9) above, wherein the microorganism belongs to the genus Escherichia, Corynebacterium, or Brevibaterium.

 (1 1) The microorganism culture of (9) or (10) above or a treated product thereof, cytosine, a phosphate group donor and an energy donor are present in an aqueous medium, and CMP is added to the medium. A method for producing CMP, characterized in that it is generated, accumulated, and CMP is collected from the medium.

 [0010]

 (12) The microorganism culture of (9) or (10) above or a treated product thereof, a culture of a microorganism belonging to the genus Corynepacteria or a treated product thereof, cytosine, phosphate group donation A method for producing CMP, comprising: a body and an energy donor in an aqueous medium, producing and accumulating CMP in the medium, and collecting CMP from the medium.

 (13) The production method according to (12) above, wherein the microorganism belonging to the genus Corynebataterium is Corynebataterum anemones.

 (14) The microbial culture of (9) or (10) above or a treated product thereof, cytosine, a phosphate donor and an energy donor are present in an aqueous medium, and CMP produced in the medium A method for producing a useful substance, characterized in that

 [001 1]

 The present invention also relates to the following (15) to (24).

 (15)

A method for producing a protein having an activity of producing cytidine 5, monomonophosphate (CMP) from cytosine, comprising the following steps:

[1] Uridine 5 'from uracil — The UMP binding site in UPRTa se on a computer using part or all of the three-dimensional structural information of the protein (UPRTa se) that has the activity to generate monophosphate (UMP) Selecting one or more amino acid deletions, substitutions and / or additions in the amino acid sequence of UPRTase to stabilize the complex model of UPRTase and CMP produced by adapting CMP to [2] A step of producing a mutant protein of UP RTase containing the deletion, substitution and / or addition selected in step [1].

 [0012]

 (16)

A method for producing a protein having an activity of producing cytidine 5′-monophosphate (CMP) from cytosine, comprising the following steps:

 [1 1] Uridine 5 '— Urine binding site in UPRTa se on the computer using part or all of the 3D structure information of protein (UPRTa se) that has the activity to generate monophosphate (UMP) Selecting one or more amino acid deletions, substitutions and Z or additions in the amino acid sequence of UPRTase, which stabilizes a complex model of UPRTase and CMP produced by adapting CMP to

 [12] Amino acid deletion, substitution and / or in the amino acid sequence of UPRTase that stabilizes a multimeric model of the complex that is created on a computer using a part or all of the complex model Selecting one or more additions;

[13] A step of producing a UPRTase mutant protein comprising the deletion, substitution and / or addition selected in the steps [11] and [12].

 (17)

 (15) A protein obtained by the method according to (16).

 [0013]

 (18)

In the amino acid sequence described in SEQ ID NO: 15, the amino acid sequence has one to several amino acids deleted, substituted and / or added,

Has the activity of generating CMP from cytosine, and

Proteins containing one or more of the following amino acid substitutions:

A part of the three-dimensional structural information of a protein (UP RTase) comprising the amino acid sequence of SEQ ID NO: 15 represented by the three-dimensional coordinate atomic coordinates described in Table 1 and having an activity of generating UMP from uracil, or In the complex model of UPRT ase and UMP created on the computer using the whole, substitution of amino acid in which the constituent atom exists in the range of 1 OA from the oxygen atom of the oxo group at the 4-position of pyrimidine ring of UMP There,

Substitution with an amino acid that stabilizes the complex model of UPRT as and CMP produced on a computer by converting the UMP group of UMP of the complex model to an amino group.

(19) The protein according to (18), wherein the amino acid substitution is a substitution of dalysin at position 205 of the amino acid sequence represented by SEQ ID NO: 15.

 [0014]

 (20)

The protein according to (18), wherein the amino acid substitution is substitution of dalicin at position 205 of the amino acid sequence represented by SEQ ID NO: 15 with aspartic acid or glutamic acid. (twenty one)

The protein according to (18), wherein the amino acid substitution is a substitution of tyrosin at position 201 and proline at position 204 of the amino acid sequence shown in SEQ ID NO: 15.

 (twenty two)

The protein according to (18), wherein the amino acid substitution is substitution of tyrosine at position 201 with lysine and substitution of proline at position 204 with leucine in the amino acid sequence shown in SEQ ID NO: 15.

 (twenty three)

In the above complex model of UPRTase and UMP, substitution of an amino acid having a constituent atom within the range of 1 OA from any atom constituting UMP (however, from the oxygen atom of the oxo group at the 4-position of the pyrimidine ring of UMP) 1) Excluding amino acid substitutions where the constituent atoms are in the range of OA), including one or more amino acid substitutions that stabilize the complex model of UPRTase and CMP (18) to

(22) The protein according to any one of (22).

 [0015]

 (twenty four)

A part of the three-dimensional structural information of a protein (UP RT ase) comprising the amino acid sequence of SEQ ID NO: 15 represented by the three-dimensional coordinate atomic coordinates described in Table 1 and having an activity of generating UMP from uracil, or An amino acid having a constituent atom in the range of 1 OA to any one of the constituents of PR PP in a complex model of UP RTase and phosphoribosyl pyrophosphate (PRP P) created on a computer using the whole The protein according to any one of (18) to (22), which is an acid substitution, and comprises one or more amino acid substitutions that stabilize the complex model.

 (twenty five)

In a multimer model of a complex created on a computer using a part or all of the complex model of UPRTase and CMP, 5 A from any atom of the adjacent UP RTase monomer. Of amino acids in which the constituent atoms are present within the range of any one of the constituent atoms of the 66 position Trp of the adjacent UPRTase monomer and the amino acids in which the constituent atoms are present within 5 A. A substitution to an amino acid that stabilizes the multimeric model. (18) The protein according to any one of (18) to (24), which contains one or more.

 The present invention further includes a protein obtained by any one of the above-described methods for producing CP RTase; DNA encoding the protein; recombinant DNA containing the DNA; microorganism containing the recombinant DNA; The present invention relates to CMP used and a method for producing useful substances produced using CMP as a substrate or via CMP.

 [Brief description of the drawings]

 0016

 FIG. 1 is a diagram showing the alignment results of amino acid sequences of various UPRTase.

 FIG. 2 is a diagram showing a complex model of a mutant Escherichia coli iUPRTase having an amino acid substitution of G205D, M141 and A143V and CMP.

 FIG. 3 is a diagram showing a tetramer model of a complex of Escherichia coli UPRTase and CMP.

 BEST MODE FOR CARRYING OUT THE INVENTION

 [001 7]

 The protein (CPRTa se) having the activity of producing cytidine 5′-monophosphate (CMP) from cytosine of the present invention is a protein (UPRTa se) having the activity of producing uridine 5′—monophosphate (UMP) from uracil. It can be obtained as a mutant protein. The UPRTase mutated protein is a protein having an amino acid sequence in which one to several amino acids are deleted, substituted and / or added in the amino acid sequence of UPRTase. Note that the term “several” means that 30 may be sufficient, 20 is preferable, and 5 is more preferable.

 [0018]

 In the present specification, the activity of generating cytidine 5′-monophosphate (CMP) from cytosine (CPRTase activity) means the activity of synthesizing CMP and pyrophosphate from cytosine and PRPP. In this specification, CPRTase may have the activity to synthesize UMP from uracil and PRP P (UPRTase activity) at the same time, but when compared by a method that can be confirmed by the method performed in the examples described later, etc. Furthermore, it is preferable that the CPRTase activity is higher than the UPRTase activity, more preferable that the CPRTase activity is 10 times higher than the UPRTase activity, and it is further preferable that the CPRTase activity does not substantially have the UPRTase activity. [0019]

For the selection of amino acid mutations to be added to UPRTase for the production of CPRTase, it is possible to create mutant proteins at random and perform screening after confirming the activity of these mutant proteins by the method described below. Amino acid mutation or The mutation means an amino acid deletion, substitution and / or addition added to the amino acid sequence of UP RTase.

 The screening method is not particularly limited. For example, Py r G (CTP synthetase), co dA (cytosine deaminase) are used by using recombinant DNA containing DNA encoding a protein having an arbitrary mutation. ), Cdd (cytidine deaminase) Escherichia coli that has lost the three enzyme activities, and the method of performing the transformation using the obtained transformant as an indicator whether or not it grows in a cytosine-containing minimal medium I can give you. It is also possible to prepare a protein having an arbitrary mutation, quantify the amount of CMP produced, and confirm the CPRTase activity.

 [0020]

 Another method for selecting amino acid mutations to be added to UPRTase for the production of CPRTase is a method using a computer model created based on the three-dimensional structural information of UPRTase. .

 [0021]

 As the 3D structure information of UPRTase, any information available to those skilled in the art may be used. Structure information obtained by crystal structure analysis or structure information that can be acquired from a database such as PDB (Protein Data Bank) Alternatively, the structure information created using a protein homology model creation program such as Insight 97 using the structure as a model may be used. Further, the three-dimensional structure information may be information on UP RT as monomers, or information on multimers such as dimers or tetramers. Further, the three-dimensional structure information may relate to a part of the UP RT as monomer or multimer, but preferably includes information on the UMP binding site described later. In addition, when the above three-dimensional information is used for creating a multimer model, it is preferable to include information on a boundary portion between monomers.

 [0022]

 In order to select amino acid mutations to be added to UPRTase, for example, a composite model of UPRTase and CMP can be created using the above-described three-dimensional structural information of UPRTase. The entire 3D structure information or a part of it may be used to create this model. When using a part, it is preferable to select a site containing at least the UMP binding site described below. Alternatively, a site considered to be involved in stabilization of the complex of UPRTase and CMP may be selected in advance, and a complex model including the site may be created.

 [0023]

UPRT ase, which uses three-dimensional structural information and is the basis for mutation, is a protein that has the activity of generating uridine 5'-monophosphate (UMP) from uracil. There is no particular limitation on the organism from which it is derived. Examples of derived microorganisms include Acholeplasma laidlawiiQ Bacteriol. (1983) 156: 192-7.), Crithidia luciliae (Comp Biochem Physiol B. (1990) 95: 159-63., Escherichia coli

(BiochimBiophys Acta. (1986) 881: 268-75., Genbank Accession No.X57104), Bacillus caldolyticus (J Bacteriol. (1994) 176: 3698-707., Genbank Accession No.X99545), Toxoplasma gondii (Proc Natl Acad Sci US A. (1995) 92: 5749-53, Genbank Accession No. U10246), Sulfolobus shibatae

(Biochim Biophys Acta. (1996) 1296: 16-22.).

-[0024]

As for the UMP binding site in UPRTa se, UPRTa se derived from Toxoplasma gondii has already been reported (EMBO J. (1998) 17: 3219-3232) _(In this UP RTase derived from Toxoplasma gondii, The carbonyl group oxygen atom at the 2-position of the pyrimidine ring in the amide hydrogen atom of phenylalanine, the hydrogen atom at the 3-position of the pyrimidine ring at the carbonyl group oxygen atom of the 234th glycine, and the amide hydrogen atom of the 229th isoleucine The pyrimidine ring stabilizes the UMP bond with the pyrimidine ring by forming a hydrogen bond with the 4-position carbonyl oxygen atom.

 [0025]

 Based on the information on the UMP binding site described in the above document, the UMP binding site can also be determined for other types of UPRTase. Specifically, the alignment of the amino acid sequence of UPRTase from Toxop lasma gondii and the amino acid sequence of UPRTase using three-dimensional structural information was performed (ClustalW [Nuceli c Acids Research 22, 4673, (1994)] European Bioinformatics Institute website http: 〃 丽 .ebi.ac.uk (available from lustalw), gene analysis software included in Genetyx (Software Development Co., Ltd.) 3D structure information UMP The binding site can be determined. As one of the analysis software parameters for alignment, you can use the Deno Retoi Direct. Figure 1 shows an example of alignment of amino acid sequences of various UPRTases including UPRTases derived from Toxoplasma gondii and Escherichia coli. From these results, it is considered that in the UPRTase derived from Escherichia coli, isoleucine at position 202, glycine at position 207, alanine at position 209, etc. are involved in the binding of the pyrimidine ring of UMP.

 [0026]

In order to create a complex model of UPRTase and CMP, it is possible to adapt the CMP to the above UMP binding site on a computer. Examples of methods for adapting CMP to the UMP binding site include the following methods. UMP is docked to the UPRT ase derived from Escherichia coli, and the structure that has been reported for the UPRT ase derived from Toxoplasma gondii has a conformation that maintains the hydrogen bond of the UPRT ase and the pyrimidine ring of UMP. After selection, use the UMP complex model created by minimizing the energy of the complex. In the above complex model, UMP is converted to CMP as CMP by substituting oxygen at the 4-position force of the pyrimidine ring of the UMP with an amino group and removing hydrogen at the 3-position of the pyrimidine ring. Furthermore, the energy minimization calculation is performed again for the model.

 In this way, a complex model of UPRT as and CMP can be created by adapting CMP to the UMP binding site. ·

 [0027]

 Selection of amino acid mutations in UPRT ase for production of CPRT ase using the complex model of UPRT ase and CMP created as described above is to select amino acid mutations in UPRT ase that stabilize the model. This can be done with

 In this specification, “stabilizing the model” means, for example, reducing ΔAG. Here, AG (free energy change) means the energy of the complex of UPRTase and UMP minus the energy of the protein alone and the energy of UMP alone, and Δ Δΰ is the value of UPRTase and CMP here. This means the AG force calculated from the complex structure minus the AG calculated from the complex structure of the mutant UPRTase and CMP. For example, when selecting mutations such as amino acid substitutions that stabilize the model, the difference between the AG of the model before and after the mutation is calculated on the computer, and the energy level after the amino acid mutation is 5 kJ / mo 1, It can be carried out by selecting a mutation that preferably decreases 20 kJ / mo 1, more preferably 50 kJ / mo 1 or more. Such calculations can be performed with the docking program Glide.

 [0028]

 In addition, selection of mutations such as amino acid substitutions that stabilize the model can be made between model components (between UPRT ase and CMP in a complex model of UPRT ase and CMP, or between monomers in a multimeric model). Etc.) can be used as indicators. In other words, a mutation that increases the affinity between components may be selected.

 [0029]

Selection of a mutation that increases affinity can be performed, for example, by visual observation of the model. Between components in the model (UPRT ase and CMP, between monomers Hydrophobic interaction, · electrostatic interaction · hydrogen bonding · π / π interaction (interaction between magnetic fields generated by ring currents of aromatic rings) · 01 / π interaction (ring current and ring of aromatic rings) Magnetic field interaction generated by electrons of the chill group) Select a mutation that increases the force S, increases, or enhances.

 [0030]

 In the complex model of UPRT as and CMP, specifically, to stabilize the model, mutations can be selected by focusing on the structural differences between UMP and CMP. UMP and CMP differ in the 4-position of the pyrimidine ring, except that UMP is an oxo group and CMP is an amino group. Therefore, for example, the center of the constituent atom exists in the vicinity of the 4-position amino group of the pyrimidine ring of CMP (about 1 OA, preferably about 8 A, more preferably about 5 A from the center of the nitrogen atom of the amino group). Affinity between UPRT ase and CMP can be increased by changing the amino acid residue of ase to an amino acid residue that interacts with the CMP amino group. In this specification, when the distance between atoms is indicated, the distance between the centers of atoms is indicated. The distance between atoms can be measured by clicking and selecting two atoms to be measured in the model displayed on graphics by Insight97. UMP and CMP differ in whether the nitrogen atom at the 3-position of the pyrimidine ring has a hydrogen atom or not. Thus, for example, a UP RT ase in which the center of the constituent atom exists in the vicinity of the nitrogen atom at the 3-position of the CMP pyrimidine ring (about 1 OA, preferably about 8 A, more preferably about 5 A from the center of the nitrogen atom). The affinity between UPRTase and CMP can be increased by changing the amino acid residue to an amino acid residue that interacts with the CMP amino group. Furthermore, it is also preferable to select a mutation by comprehensively judging the amino acid residues of UPRT as near the 4th and 3rd positions of the pyrimidine ring. This is because UMP and CMP can be thought that the relationship between the 2- and 3-position hydrogen bond donors and acceptors of the pyrimidine ring is reversed.

 Mutations selected by focusing on the structural differences between UMP and CMP are most likely to contribute to the stabilization of the complex model of UPRTase and CMP, and are the key to the change in UPRTase activity. It is thought that.

 [0031]

For example, in Escherichia coli UPRTase, the 205 position Gly is changed to, for example, Asp or Glu. As a result, an electrostatic interaction occurs between this Asp or Glu residue and the amino group of cytosine, thereby stabilizing the complex model. sell. In addition, by using 201-position Tyr as Lys, the shape of the binding site becomes a flat shape suitable for the binding of the pyrimidine ring, and the complex model can be stabilized. In the present specification, for example, substitution of Gly at position 205 with Asp is G205D, In some cases, a single letter abbreviation is used to indicate the amino acid before mutation, followed by the amino acid after mutation.

 [0032]

 A complex model of UPRT a s e and UMP can also be used to select mutations that stabilize the complex model of UP R a s e and CMP. Since the binding position of UMP and CMP is considered to be almost the same, by using the complex model of UMP and UP RT ase created directly from the above three-dimensional structure information, CMP and CMP are substantially This is because the amino acid involved in the UPRTase interaction can be selected. In this model, for example, an amino acid residue in the vicinity of the 4-position oxo group of the pyrimidine ring of UMP (1 from the center of the oxygen atom of the oxo group)

An amino acid residue in which the center of the constituent atom is present at about 0 A, preferably about 8 A, more preferably about 5 A can be selected. The amino acid after mutation may be selected assuming that the 4-position oxo group of the pyrimidine ring is replaced with an amino group. In addition, an amino acid residue in the vicinity of the nitrogen atom at the 3-position of the pyrimidine ring of UMP (an amino acid residue in which the center of the constituent atom exists about 10 A, preferably about 8 A, more preferably about 5 A from the center of the nitrogen atom) ) Can be selected. The amino acid after mutation may be selected on the assumption that the hydrogen atom bonded to the nitrogen atom at the 3-position of the pyrimidine ring disappears.

 0033

 A complex model of UPRTase and cytosine or uracil can also be used to select a mutation that stabilizes the complex model of UPRTase and CMP. In EMBO J. (1998) 17: 3219-3232 mentioned above, the uracil bond in U P R T a s e is reported. Create a complex model of UPRTa se and cytosine or uracil in the same manner as the complex model of UPRTa se and CMP, or the complex model of UPRT ase and UMP. A mutation that stabilizes can be selected.

 [0034]

 For the production of CPRTase, a complex model of the mutation UPRTase and CMP having the mutation selected as described above is prepared in the same manner as described above, and additional amino acid mutations that stabilize the model are prepared. You may choose. Alternatively, based on the amino acid sequence of the mutation UPRTase having a mutation selected using any one of the above complex models, random screening can be performed to obtain CPRTase with higher activity.

For example, in accordance with the screening method described above, DNA having a mutation selected as described above is used as a saddle type DNA encoding the mutation UPRTase, and DNA having random mutations is prepared by the error-prone PC method. Recombination including Screening can be carried out using transformants prepared using body DNA.

 [0035]

 In addition to the mutations selected by focusing on the structural differences between UMP and CMP using the complex model of UP RT ase and CMP or the complex model of UPRT ase and UMP, other models Mutation that stabilizes can be selected. It is preferable that other mutations coexist with mutations selected by focusing on the structural differences between UMP and CMP. As another selection, for example, in the complex model of UP RTase and CMP, within the range of about 1 OA, preferably about 8 A, more preferably about 5 A from the center of any atom constituting CMP For example, the amino acid residue of UP RTase in which the center exists can be changed to an amino acid residue that interacts with the CMP amino group. Similarly, in the complex model of UPRTase and UMP, the center of the constituent atom exists in the range of about 10 A, preferably about 8 A, more preferably about 5 A from the center of any atom constituting UMP. An amino acid residue of UP RTase can be selected as an amino acid residue to be mutated.

 [0036]

 For selection of other mutations, it is also possible to create a complex model of PRPP and UPRTase, another substrate of CPRTase, and select a mutation that stabilizes the model. . It is preferable that the mutations selected in this way coexist with the mutations selected by focusing on the structural differences between the above UMP and CMP.

 [0037]

 It is known that UPRTase usually has a dimer-forming force S and GTP, which binds to form a tetramer, increasing the number of amino acids that interact with PRP P and increasing UPRTase activity (Proc Natl. Acad. Sci. USA (2002) 99: 78-83.). A similar trend can be predicted for CPRT a s e, so it can be predicted that CPRT a s e activity is also increased by mutations that stabilize multimers. Therefore, amino acid mutations added to UPRTase for the production of CPRTase can be performed by selecting mutations that stabilize UPRTase or any of the aforementioned multimeric models of the complex. it can.

 [0038]

Mutations that stabilize the multimeric model include examining the amino acid at the boundary between each monomer on computer graphics and energeticly unstable elements between them (for example, electrostatic repulsion, three-dimensionality). Mutations that remove unstable elements or enhance interactions. Example For example, an amino acid having a center of a constituent atom in the range of about 1 OA, preferably about 8 A, more preferably about 5 A from any atom of the adjacent UP RTase monomer is added to the adjacent atom. It can be changed to an amino acid residue that interacts with the UP RTase monomer.

 [0039]

 Also, as described in EMBO J. (1998) 17: 3219-3232, the i3 arm consisting of the second and third strands (Β2, Β3) and the second of the other monomer The dimer is formed by the interaction between the third and fourth α-helices (Α2, A3, Α4). Therefore, these areas including the J3 arm

 It may be possible to select mutations focusing on (B2, B3, A2, A3, A4).

 The multimer model may be created based on the three-dimensional structure information of UPRTase or preferably one of the complex models described above. In particular, since the multimeric structure is thought to contribute to increasing the binding site with the substrate, it is also preferable to create the multimeric model using all or part of the complex model of UPRTase and PRPP.

 [0040]

 Random screening can be performed based on the UPRTase mutant protein having the mutation selected as described above to obtain CPRT ase having higher activity.

 In addition to the mutations selected as described above, the mutant protein of UPRTase obtained as CPRTa se is introduced as a secondary mutation, as well as substitution with mutually convertible amino acids as described below. Other mutations may be included. The production method of the variant protein is not particularly limited, but it can be produced by a method using genetic recombination described in the production of a specific protein described later.

 [0041]

 1. Protein of the present invention (CPRTa s e)

 Examples of CP RT as of the present invention include the proteins described in the following (a) to (d).

 (a) a protein having an amino acid sequence represented by SEQ ID NO: 1, 2, or 30 having an activity of generating CMP from cytosine,

 (b) selected from the 36th, 94th, 102th, 141st, 143rd and 198th amino acid residues in the amino acid sequence represented by SEQ ID NO: 1, 2, or 30—one or more A protein having an amino acid sequence in which an amino acid residue is substituted with another amino acid residue, and having an activity of generating CMP from cytosine;

(c) The 36th amino acid residue is cysteine, the 94th amino acid residue is tyrosin, the 102nd amino acid residue is cysteine, and the 141st amino acid residue is Leucine, a protein of (b) above having an amino acid sequence in which the 1st to 3rd amino acid residues are substituted with valine, or the 1st to 8th amino acid residues of glycine, and (d) the above (a) to (c) 3 6th, 9 4th, 1 0 2nd, 1 4 1st, 1 4 3rd, 1 9 8th, 2 0 1st, 2 0 4th and 2 0 A protein having an amino acid sequence in which one or more amino acid residues selected from amino acid residues other than the fifth amino acid residue are substituted with other amino acid residues, and having an activity of generating CMP from cytosine;

Etc.

 [0 0 4 2]

 The “other amino acid residue” in (b) and (d) above may be either a natural amino acid or a non-natural amino acid. Natural amino acids include L-alanine, L-asparagine, L-aspartic acid, L-glutamine, L monoglutamic acid, glycine, L-histidine, L-isoleucine, L-leucine, L-lysine, L-arginine, L -Methionine, L-phenylalanine, L-proline, L-serine, L-threonine, L-tryptophan, L-tyrosine, L-valine, L-cysteine, etc.

 [0 0 4 3]

 Preferably, as the other amino acid residues in (b) above, the 36th amino acid residue is cysteine, the 94th amino acid residue is tyrosine or phenylalanine, and the 102nd amino acid residue is cysteine. 1 4 The first amino acid residue is derived from oral isine, isoleucine, norleucine, valine, norpaline, alanine, 2-aminobutanoic acid, methionine, O-methylserine, t-butylglycine, t-butylalanine and cyclohexanalanalanin Selected amino acids, 1 4 3rd amino acid residue is valine, leucine, isoleucine, norleucine, norpaline, alanine, 2_aminobutanoic acid, methionine, 0-methylserine, t-butylglycine, t-butylalanine and cyclohe Amino acid selected from xylalanin, 1 9 8th amino acid residue is glycine Can.

 [0 0 4 4]

 Examples of amino acids that can be substituted for each other in the protein (d) are shown below. Amino acids included in the same group can be substituted for each other.

 Group A: Leucine, Isoleucine, Norleucine, Norrin, Norpaline, Alanine, 2-Aminobutanoic acid, Methionine, O-Methylserine, t-Butylglycine, t-Butylalanin, Cyclohexylalanin

 Group B: aspartic acid, gnoretamic acid, isoaspartic acid, isodartamic acid, 2-aminoadipic acid, 2-aminosuberic acid

Group C: Asparagine, glutamine Group D: Lysine, Arginine, Ornitine, 2,4-Diaminobutanoic acid, 2,3-Diaminopropionic acid

 Group E: Proline, 3-hydroxyproline, 4-hydroxyproline

 Group F: serine, threonine, homoserine

 Group G: Phenylalanin, tyrosine

 The fact that the proteins (b) and (d) above have the activity of generating CMP from cytosine is that Pyr G (CTP synthetase) is used using recombinant DNA containing DNA encoding the protein. , Co dA (cytosine deaminase), cdd (cytidine deaminase) E. coli lacking three enzyme activities are transformed, and the resulting transformant grows in a cytosine-containing minimal medium. This can be confirmed by being able to do so.

 2. DNA of the present invention

 The DNA of the present invention includes the DNAs described in the following (e) and (f)

 (e) DNA encoding the protein of the present invention of 1 above, and

 (f) DNA having the base sequence represented by any of SEQ ID NOs: 3 to 5

Etc.

 3. Preparation of DN A of the present invention

 The DNA of the present invention can be obtained by introducing a mutation into DNA encoding UPR T ase derived from Escherichia coli.

 (1) Acquisition of DNA encoding UP RT ase derived from Escherichia coli Escherichia's method of obtaining DNA encoding UPRT ase derived from E. coli is the method of Saito et al. From E. coli [Biochim. Biophys. , 72, 619 (1963)] using a primer DNA that can be designed and synthesized based on the nucleotide sequence represented by SEQ ID NO: 5 using a chromosomal DNA that can be prepared according to SEQ ID NO: 5, etc. Can give.

 [0045]

 Specifically, chromosomal DNA is prepared from Escherichia coli W3110 strain, and DNA having the nucleotide sequences represented by SEQ ID NOs: 6 and 7, for example, is chemically synthesized using the DNA as a cage, and the DNA is used as a primer set. It can be obtained by PCR. Specific DNA that can be obtained by the above method includes DNA having the base sequence represented by SEQ ID NO: 5.

 [0046]

In addition, DNA encoding UP RT ase derived from Escherichia coli is also obtained by a hybridization method using a part or all of the DNA consisting of a base sequence complementary to the base sequence represented by SEQ ID NO: 5 as a probe. Can get it can. The hybridization method can be performed in accordance with the method described in Molecular Cloning, A Laboratory Manual, Third Edition, Cold Spring Harbor Laboratory Press _x 2001 (hereinafter abbreviated as molecular cloning). .

 [0047]

 Furthermore, DNA encoding UP RT ase derived from Escherichia coli can also be obtained by chemically synthesizing DNA having the base sequence by a known method based on the base sequence represented by SEQ ID NO: 5.

 (2) Preparation of DN A of the present invention

 The DNA of the present invention can be obtained by adding molecular cloning and Current Protocols in Molecular Biology, John Wiley & Sons (1987-1997) (hereinafter referred to as “DNA” encoding UP RTase derived from Escherichia coli obtained in (1) above). It can be obtained by introducing a site-specific mutation according to the method described in Current Protocols' In Molecular Biology and Abbreviations, etc. In addition, the error-prone PCR method [Proc. Sci. USA, 90, 5618 (1 982)] can also be obtained by introducing a random mutation into DNA having the base sequence represented by SEQ ID NO: 5.

 [0048]

 In addition, a complex structure of UPRT ase and UMP such as Toxoplasma gondii and Bacillus caldolyticus derived from various organisms is used as a model, and a homology model of Escherichia coli is created based on this model. Extract amino acid residues in the vicinity of the UMP binding site, select amino acid residues presumed to play an important role in converting substrate specificity from the original substrate uracil to cytosine, and site-specific It is also possible to select a protein having an activity of converting cytosine to CMP by introducing a genetic mutation. For details, refer to the description of “CP RT as design” above.

4. Production of the protein of the present invention

 The protein of the present invention of 1 above is obtained by using the method described in Molecular Cloning Current Protocols 'In' Molecular Biology etc., for example, by It can be made to express in.

 [0049]

That is, based on the DNA that can be obtained by the above method 3, a DNA fragment of an appropriate length containing a portion encoding the protein of the present invention is prepared as necessary, and the DNA fragment is used as an appropriate expression vector. A recombinant DNA inserted downstream of the promoter of To make. A transformant can be prepared by introducing the silkworm recombinant DNA into a host cell suitable for the expression vector.

 [0 0 5 0]

 In addition, the protein of the present invention can also be efficiently produced by preparing DNA in which the base sequence of the DNA fragment is substituted so that it is an optimal codon for host cell expression.

 Any host cell can be used as long as it can express the target gene. As the expression vector, a vector that can replicate autonomously in the above-described host cell and contains a promoter at a position where the DNA encoding the polypeptide of the present invention can be transcribed is used.

 [0 0 5 1]

 When a prokaryotic organism such as a bacterium is used as a host cell, the recombinant vector containing the DNA encoding the protein of the present invention is capable of autonomous replication in a prokaryotic organism, and at the same time a promoter, a ribosome binding sequence, A vector composed of the DNA of the present invention and a transcription termination sequence is preferred. It may contain a gene that controls the promoter.

For example, when a microorganism belonging to the genus Escherichia is used as a host cell, pBTrp2, pBTacl, pBTac2 (all available from Boehringer Mannheim), pTrc99A (Pharmacia), pSE280 (Invitrogen), pGEM EX-1 (Promega), QE82L (QIAGEN), pKYPIO (JP-A 58-110600), pKYP200 [Agric. Biol. Chem., 48, 669 (1984)], pLSAl [Agric. Bi ol. Chem., 53, 277 (1989)], pGELl (Proc. Natl. Acad. Sci. USA, 82, 430 6 (1985)), pBluescript II SK (-) (Stratagene), pTrs30 [Escherichia E. coli JM109 / pTrS30 (FERM BP-5407)], pTrs32 (Escherichia coli i Prepared from JM109 / pTrS32 (FERM BP-5408)), pGHA2 [Escherichia coli IGHA2 (FERM BP-400), No. 221091), pGKA2 (prepared from Escherichia coli IGKA2 (FERM BP-6798), JP 60-221091), pTerm2 (US 4686191, US4939094, US5160735), pSupex, pUB110, pTP5, pC194, pEG400 [J. Bacteriol., 172, 2392 (1990)], pGEX (Pharmacia), pET system (Novagen), etc., and the host cell belongs to the genus Corynebacterium In the case of using microorganisms, pCGl (Japanese Unexamined Patent Publication No. 57-134500), pCG2 (Japanese Unexamined Patent Publication No. 58-35197), pCG4 (Japanese Unexamined Patent Publication No. 57-183799), pCGll (Japanese Unexamined Patent Publication No. 57-134500). 134500 JP), pCG116, pCE54, pCBlOl (both JP 58-105999 discloses), pRIl 09 (re Table 2000- 44886 discloses: WOOO / 44886), pCE51, P CE52, pCE53 [ both M Olecular and General Genetics, 196, 175 (1984)]. [0 0 5 2]

Any promoter can be used as long as it functions in the host cell. For example, trp promoter (P _TRD), lac promoter, P _L promoter, P _R promoter, can be mentioned promoter one terpolymer derived from such T7 promoter, E. coli or phage, or the like. In addition, artificially designed and modified promoters such as two promoters in series (PX 2), tac promoter, lacT7 promoter, let I promoter, and the like can also be used.

 [0 0 5 3]

 It is preferable to use a plasmid in which the distance between the Shine-Dalgarno sequence, which is a ribosome binding sequence, and the start codon is adjusted to an appropriate distance (eg, 6 to 18 bases). In the recombinant vector of the present invention, a transcription termination sequence is not necessarily required for the expression of the DNA of the present invention, but it is preferable to arrange the transcription termination sequence immediately below the structural gene.

Host cells include microorganisms belonging to Escherichia, Corynebacterium, or Brevibacterium, such as Escnerichia coli, Gorynebacterium ammoniagenes ^ Corvneo acterium glutamicum ^ Brevibacterium iramariophilum, Brevibacterium iramariophilum sacch arolyticum ^ Brevibacterium f lavum and Brevibacterium lactofermentum and the like can be mentioned, more preferably Escherichia coli XL1- Blue, Escheri chia coli X and 2 - Blue, Escherichia coli DH1, Escherichia coli DH5 CK, Esche richia coli MCI 000 Λ Escherichia coli MM294, Escherichia coli W1485, Esc herichia coli JM109, Escherichia coli HB101, Escherichia coli No. 49, Es cherichia coli W3110, Escherichia coli NY49, Escherichia coli GI698, Corynebacterium ammoniagenes ATCC6872, Corynebacterium ammoniagenes ATCC2 1170, Corynebacteriummicv glutamicum ATCC21171, B revibacterium immariophilum ATCC 14068 _¾ Brevibacterium sacch arolyticum ATC 14066, Brevibacterium f lavum ATCC14067, Brevibacterium 1 actofermentum ATCC13869, etc., more preferably Corynebacterium ammoniagenes ATCC21170, Corvnebacterium glutamicum ATCC21171.

 [0 0 5 4]

As a method for introducing a recombinant vector, any method can be used as long as it is a method for introducing DNA into the host cell. For example, a method using calcium ions [Proc. Natl. Acad. Sci. USA, 69, 2110 ( 1972)], protoplast method (JP-A 57-186492, JP-A 57-18649), electroporation [for example, Journa 1 of Bacteriology, 175, 4096 (1993), Appl. Microbiol. Biotechnol. , 52. 541 (1999)], Gene, 17, 107 (1982) and Molecular & General Genetics, 168, 111 (1979).

 [0 0 5 5]

 As a form of production of the protein of the present invention, in addition to producing it as it is, it can be produced as a secreted production or fusion protein according to the method described in Molecular Cloning.

 The protein of the present invention can be obtained by culturing the transformant obtained by the above method in a medium, producing and accumulating the protein of the present invention in the culture, and collecting the protein of the present invention from the culture. Can do.

 [0 0 5 6]

 The transformant can be cultured by a normal culture method.

 As a medium for culturing, a natural medium or a synthetic medium may be used as long as it contains a carbon source, a nitrogen source, and an inorganic salt that can be assimilated by the transformant, and can efficiently culture the transformant. Any of these may be used.

 As the carbon source, for example, sugars such as glucose, fructose, sucrose, maltose and starch hydrolysate, alcohols such as ethanol, and organic acids such as acetic acid, lactic acid and succinic acid can be used. The concentration is preferably 5 to 400 g / l.

 [0 0 5 7]

 Nitrogen sources include ammonia, ammonium chloride, ammonium sulfate, ammonium carbonate, ammonium acetate, various inorganic and organic ammonium salts, urea, other nitrogen-containing compounds, meat extract, yeast extract, corn steep liquor, Nitrogen-containing organic substances such as soybean hydrolyzate can be used. The concentration is preferably 1-100 g / l.

 Examples of inorganic salts include primary hydrogen phosphate lithium, secondary hydrogen phosphate lithium, ammonium sulfate, sodium chloride, magnesium sulfate, calcium carbonate, and the like.

 [0 0 5 8]

 In addition, trace nutrient sources such as piotin and thiamine can be added as needed. These micronutrient sources can be substituted with natural products such as meat extract, yeast extract, corn 'steep' liquor and casamino acids.

Cultivation is performed under aerobic conditions such as shaking culture and deep aeration stirring culture. Culture temperature is 20 ° (:. ~ 50 ° C, preferably preferably 30 ° C~42 ° C, pH of the medium is 4 to 10, good Mashiku is maintained at 5-8 Adjustment of _P H is , Using inorganic or organic acid, alkaline solution, urea, calcium carbonate, ammonia, etc. Culturing time is 12 to 6 days, preferably 1 to 3 days. Antibiotics such as may be added to the medium. [0 0 5 9]

 When cultivating microorganisms transformed with a recombinant vector using an inducible promoter as a promoter, an inducer may be added to the medium if necessary. For example, when cultivating a microorganism transformed with a recombinant vector using a promoter, when culturing a microorganism transformed with isopropyl-β-D-thiogalatatoviranoside, etc. Indoleacrylic acid or the like may be added to the medium.

 [0 0 6 0]

 As a method for producing the protein of the present invention, there are a method of producing in the host cell, a method of secreting it outside the host cell, and a method of producing it on the host cell outer membrane.

 When the protein of the present invention is produced in the host cell or on the host cell outer membrane, the method of Paulson et al. [J. Biol. Chem., 264, 17619 (1989)], the method of Lou et al. [Proc. Natl Acad. Sci. USA, 86, 8227 (1989), Genes Develop., 4, 1288 (199 0)], or by applying the method described in JP-A-5-336963, W094 / 23021, etc. The protein can be actively secreted outside the host cell.

 [0 0 6 1]

 That is, by using a gene recombination technique, the protein of the present invention can be actively expressed outside the host cell by expressing in a form in which a signal peptide is added in front of the polypeptide containing the active site of the protein of the present invention. Can be secreted.

 Further, according to the method described in Japanese Patent Application Laid-Open No. 2-227075, the production amount can be increased using a gene amplification system using a dihydrofolate reductase gene or the like.

 [0 0 6 2]

 In order to isolate and purify the protein produced by the transformant of the present invention, a usual enzyme isolation and purification method can be used.

For example, when the protein of the present invention is expressed in a dissolved state in cells, the cells are collected by centrifugation after culturing, suspended in an aqueous buffer solution, an ultrasonic crusher, a French press, Manton Gaurin. Crush the cells with a homogenizer, dynomill, etc. to obtain a cell-free extract. From the supernatant obtained by centrifuging the cell-free extract, an ordinary enzyme isolation and purification method, that is, a solvent extraction method, a salting-out method using ammonium sulfate, a desalting method, a precipitation method using an organic solvent, Jetylaminoethyl (DEAE) — Sepharose, DIAION HPA-75 (manufactured by Mitsubishi Kasei Co., Ltd.) and other anion-exchange chromatography using a resin, S- Sepharose FF (Pharmacia) etc. Cation exchange chromatography, hydrophobic chromatography using resins such as butyl sepharose and phenycephalose, gel filtration using molecular sieves, affinity chromatography, chromatofocusing, isoelectric A purified product can be obtained by using a method such as electrophoresis such as point electrophoresis alone or in combination.

 [0 0 6 3]

 In addition, when the protein is expressed in an insoluble form in the cell, the insoluble form of the protein can be recovered as a precipitate fraction by similarly collecting the cell, crushing, and centrifuging. . Solubilize the recovered protein insolubles with a protein denaturant. The protein can be returned to a normal three-dimensional structure by diluting or dialyzing the solubilized solution and reducing the concentration of the protein denaturant in the solubilized solution. After the operation, a purified sample of the protein can be obtained by the same isolation and purification method as described above.

 [0 0 6 4]

 When the protein of the present invention or a derivative such as a protein having a sugar chain added to the protein is secreted extracellularly, the protein or the protein derivative can be recovered in the culture supernatant. That is, a culture supernatant is obtained by treating the culture by a method such as centrifugation as described above, and a purified sample is obtained from the culture supernatant by using an isolation purification method similar to the above. Can be obtained.

 [0 0 6 5]

 As the protein thus obtained, the above protein 1 can be mentioned.

 5. Manufacturing method of CMP of the present invention

 A culture of the transformant obtained by the above method 4 or a treated product of the culture, cytosine, a phosphate group donor and an energy donor are present in an aqueous medium, and CMP is produced in the medium; The CMP can be acquired by accumulating and collecting the CMP from the medium.

 [0 0 6 6]

 Further, a culture of a transformant obtained by the above method 4, a treated product of the culture, a culture of a microorganism belonging to the genus Corynepacteria, or a treated product of the culture, cytosine, a phosphate group donor CMP can also be obtained by allowing the energy donor to be present in an aqueous medium, generating and storing CMP in the medium, and collecting CMP from the medium.

 As a method for culturing the transformant, a method similar to the method for culturing the transformant described in 4 above may be used. The transformant is used as wet cells at a concentration of 0.5 to 500 g / l, preferably 5 to 200 g / l.

 [0 0 6 7]

The cytosine used as a substrate may be synthetic or natural. In addition, if it contains cytosine, refined products, cytosine-containing crude products obtained from natural products, etc. Either is acceptable. Cytosine is used at a concentration of 1 to 100 g / l, preferably about 1 to 50 g / l.

 Energy donors include glucose, fructose, sucrose, molasses, starch hydrolyzed carbohydrates, pyruvic acid, lactic acid, acetic acid, organic acids such as ketoglutaric acid, amino acids such as glycine, alanine, aspartic acid, and glutamic acid. Any substance can be used as long as it can metabolize the above-described transformant and produce ATP in the cell. These are used at a concentration of 5 to 200 g / l.

 [0 0 6 8]

 Phosphoric acid group donors include orthophosphoric acid, pyrophosphoric acid, tripolyphosphoric acid, tetrapolyphosphoric acid, tetrapolymetaphosphoric acid, etc., polymetaphosphoric acid, monopotassium phosphate, dipotassium phosphate, monosodium phosphate, phosphoric acid Inorganic phosphates such as disodium can be listed. These are used at a concentration of 1-50 g / l.

 Examples of microorganisms belonging to the genus Corynebacterium include Corynebacterium ammoniagenes and Corynebacterium glutamicum, and more preferable examples include Corynebacterium ammonia¾enes ATCC6872, Corynebacterium aramoniagenes ATCC21170, Corynebacterium glutamicum ATCC13032, Corynebacterium glutamic icum ATCC21171 and the like. Microorganisms belonging to the genus Corynebacterium can be cultured in the same manner as in 4 above. Microorganisms belonging to the genus Corynebatarum are used as wet cells at a concentration of 0.5 to 500 g / l, preferably 5 to 200 g / l.

 [0 0 6 9]

 Examples of the aqueous medium include aqueous solutions containing salts and salts that do not inhibit the CMP production reaction, such as water, phosphate buffer, tris buffer, and borate buffer. In addition, the supernatant of a culture obtained by culturing a transformant or a microorganism belonging to the genus Corynebataterium can be used as an aqueous medium as it is.

 Further, a surfactant or an organic solvent may be added to the aqueous medium as necessary. By adding a surfactant or an organic solvent, the production efficiency of CMP can be increased.

 [0 0 7 0]

Examples of surfactants include cationic surfactants such as polyethylene glycol stearylamine (eg, Nimine S-215, manufactured by Nippon Oil & Fats Co., Ltd.) and alkyldimethylbenzyl ammonium mucolide (eg, Sanizol B-50, manufactured by Kao Corporation). Anionic surfactants such as sodium lauryl sulfate (for example, Persoft SL, manufactured by NOF Corporation), polyethylene glycol sorbitan monostearate (for example, Nonionic surfactants such as nonionic ST221 (manufactured by NOF Corporation) and amphoteric surfactants such as dimethyllauryl betaine (eg NISSAN ANON BL, manufactured by NOF Corporation), etc. It is used at a concentration of ˜20 g, preferably 1 to 10 g / l.

 [0 0 7 1]

 Examples of the organic solvent include toluene, xylene, aliphatic alcohol, acetone, ethyl acetate and the like, and these are usually used at a concentration of 0.1 to 50 ml / l, preferably 1 to 20 ml / l.

 The production reaction of CMP is carried out under aerobic conditions such as by aeration stirring. The reaction temperature is maintained at 20 ° C to 50 ° C, preferably 30 ° C to 42 ° C, and the pH in the medium is maintained at 4 to 10, preferably 5 to 8. The pH is adjusted using inorganic or organic acids, alkaline solutions, urea, calcium carbonate, ammonia, etc. The reaction time is usually 1 to 48 hours.

 [0 0 7 2]

 After completion of the reaction, CMP can be isolated and purified from the reaction solution obtained by removing precipitates such as bacterial cells by using a known method such as activated carbon treatment or ion exchange resin treatment.

 In addition, in the method for producing useful substances produced by using CMP as a substrate or via CMP, it was collected from CMP or aqueous medium produced and accumulated in an aqueous medium by the CMP production method of the present invention. CMP can be used.

 Examples of useful substances produced as described above include cytidine mono 5′-triphosphoric acid, CMP-sialic acid, C D P-choline and the like.

 Examples of a method for producing cytidine 15,5 tritriphosphate using CMP as a substrate include the methods described in JP-A-2002-085087 and JP-A-2000-217593, and CMP-sialic acid. As a method for producing CDP-choline, for example, methods described in JP-A-5-276973, W02004009830 and JP-A-2002-085087 can be mentioned. -313 The method described in 594 gazette and Japanese Patent Publication No. 48-2358 gazette can be mentioned. 【Example】

 Examples of the present invention are shown below, but the present invention is not limited to these Examples.

 [0 0 7 3]

Example 1

Construction of host bacteria for activity detection

The host strain MC1000 A codA Acdd A pyrG:: Km was constructed as follows to detect the enzymatic activity to produce CMP from cytosine and phosphoribosyl pyrophosphate (PRPP). (1) Preparation of a strain deficient in the gene encoding cytosine deaminase (codA gene) and the gene encoding cytidine deaminase

 A strain lacking the codA gene and cdd gene on the chromosomal DNA of Escherichia coli MC1000 can be obtained by a method using the homologous recombination system of lambda phage (Proc. Natl. Acad. Sci. USA, 97, 6640-6645 (2000)) It produced according to.

 [0 0 7 4]

The chromosomal DNA of Escherichia coli MCI 000 was cultivated by a known method, and isolated and purified by the method described in “Rent Protocols” in ”Molecular Biology after cultivation. Plasmid _P KD46, pKD3, 'pKD4 and pC P20 were obtained from the Escherichia coli strain carrying the plasmid from the Escherichia coli Collagenetic Stock Center (Yale University, USA) and extracted from the Escherichia coli. Was used.

 [0 0 7 5]

 Of the nucleotide sequence containing the Escherichia coli codA gene represented by SEQ ID NO: 6, the nucleotide sequences represented by nucleotide numbers 1-1031 and 2094-3105 were amplified by PCR reaction. These amplified fragments have pKD4 as a saddle and have FRT (FLP recognition target) sites at both ends obtained by amplifying DNA consisting of the nucleotide sequences represented by SEQ ID NOs: 7 and 8 as a primer set. (ami nog lycoside phosphotransferase) Ligated with iiis fragment.

 [0 0 7 6]

 The ligated fragment was introduced by electroporation into Escherichia coli MC1000 strain into which pKD46 had been introduced in advance and λ Red recombinase was induced and expressed. A transformant was selected using kanamycin resistance as an index, and a strain in which the L gene was inserted into the codA gene on the chromosome to destroy the gene was obtained.

 Next, of the base sequence containing the Escherichia coli cdd gene represented by SEQ ID NO: 9, the base sequence portions represented by the base numbers 1-1011 and 1656-2572 were amplified by PCR reaction. These amplified fragments were obtained by amplifying pKD3 as a saddle, using the DNA consisting of the nucleotide sequences represented by SEQ ID NOs: 10 and 11 as a primer set, and having FRT sites at both ends. The (chloramphenicol acetyltrans ferase) gene fragment was ligated.

 [0 0 7 7]

The ligated fragment was introduced by the electroporation method into the kanamycin resistant strain obtained as described above in which λ Red recombinase was inducibly expressed. Transformants were selected using kanamycin and kulam lamfenicol resistance as indicators, and a strain in which the cat gene was disrupted by insertion of the cat gene into the gene on the chromosome was obtained. After removing pKD46 from the kanamycin and chloramphenicol resistant strains obtained above, pCP20 was introduced, FLP recombinase was induced and cultured, and then the strain from which the gene was removed from the chromosomal DNA After selecting Ramfenicol sensitivity as an index, pCP20 was removed.

 [00 78]

 The strain obtained by the above operation is the 1032-2093 in the nucleotide sequence represented by SEQ ID NO: 6 on the chromosomal DNA of Escherichia coli MC1000 strain, and 1012-1655 in the nucleotide sequence represented by SEQ ID NO: 9. The Escherichia coli iMC1000 strain lacking the portion corresponding to the nucleotide sequence represented by No. 1, ie, lacking the codA gene and the cdd gene, was named Escherichia coli MClOOOAcodAAcdd.

(2) Preparation of CTP synthase-encoding gene (pyrG gene) disrupted strain

 From the chromosomal DNA of Escherichia coli strain MM294, a DNA consisting of the nucleotide sequence represented by the IJ number 12 that is part of the yrG gene was prepared according to a conventional method. Connected between.

 [00 79]

 The resulting recombinant plasmid DNA was digested with and then smoothed, and PUC4K (purchased from Amersham Biosciences) digested with ^ πΗΙ and smoothed, containing about 1.3 kb containing the gene derived from PUC4K. And ligated with the DNA fragment.

 The obtained plasmid DNA was digested with ΠΐΗΙ and ^ nl and purified to obtain a defective eiil gene fragment in which the aph gene was inserted into the gene and the gene was destroyed.

 [0080]

 The DNA fragment was introduced into Escherichia coli JC7623 by electroporation, a transformant was selected using kanamycin resistance as an indicator, and a strain exhibiting cytidine requirement was isolated.

 According to a conventional method, PI lysate is prepared from the isolated strain, infected with 294 Escherichia coli strains, and a strain exhibiting resistance to kanamycin is selected. A strain in which the above gene was disrupted was obtained, and the strain was named Escherichia coli MM294ApyrG :: Km.

 (3) Preparation of Escherichia coli MC1000 AcodA Acdd Δ pyrG :: Km strain

 According to a conventional method, PI lysate was prepared from the Escherichia coli MM294 pyrG :: Km strain obtained in (2) above, infected with the MClOOOAcodAAcdd strain obtained in (1) above, and the transduced strain was selected using kanamycin resistance as an indicator. Selected. The obtained transduced strain was a strain in which the codA gene and the cdd gene were deleted and the pyrG gene was disrupted, and the strain was named Escherichia coli MClOOOAcodAAcddApyrG :: Km.

[008 1] Escherichia coli MC1000 AcodA Acdd ApyrG:: Km strain is Cytidine-required, M 9 minimal agar medium containing 50 mg / l cytosine [glucose 1.8 g, sodium monohydrogen phosphate 6 g, dihydrogen phosphate 3 g, salt Contains 11 g of sodium chloride 0.5 g, ammonium chloride lg, magnesium sulfate heptahydrate 0.25 g, calcium chloride dihydrate 15 mg, thiamine hydrochloride 10 mg, Agar-Noble (Difco) 20 g] It was confirmed that it could not grow. That is, a transformant obtained by introducing a plasmid expressing a mutant UPRTase into Escherichia coli MCI 000 厶 codA Acdd ApyrG:: Km strain has the activity that the mutant enzyme generates CMP from cytosine. Can grow on M9 minimal medium containing cytosine only if

 [0082]

Example 2

 Cloning of wild-type UP RT as from Escherichia coli

 First, a chromosomal DNA of Escherichia coli W3110 strain is prepared by a known method, and then the chromosomal DNA is used as a saddle and DNA comprising the nucleotide sequence represented by SEQ ID NOs: 13 and 14 is used as a primer set. PCR was performed using Pyrobest DNA polymerase (Takara Shuzo).

 [0083]

 The approximately 0.7 kb amplification product obtained by PCR was purified using Qiagen PCR Purificatin Kit (manufactured by Qiagen) and cleaved with 1 and ίΗΙ. The restriction enzyme-treated product was subjected to agarose gel electrophoresis, and then extracted and purified using Qiagen Gel Extraction Kit (manufactured by Qiagen).

 The DNA fragment was ligated with the expression vector pTrc99A (manufactured by Pharmacia), which was also cleaved with EcoRI and BamHI, using DNA Ligatin Kit ver.2.0 (manufactured by Takara Shuzo). DH5a (Toyobo Co., Ltd.) was transformed.

 [0084]

 A transformant was selected using ampicillin resistance as an indicator, and the obtained transformant was cultured overnight in an LB medium containing 10 Ο / g / ml ampicillin. From the obtained culture, plasmid DNA is prepared using Qiagen Plasmid Miniprep Kit (Qiagen), and the nucleotide sequence is analyzed, so that the plasmid contains the target Escherichia coli UPRTase gene. It was confirmed that the plasmid had a structure in which a DNA fragment of about 0.7 kb was inserted, and the plasmid was named pEUPl.

 [0085]

Example 3

Example of 3D structure information of UPRTa se Crystal structure analysis of wild-type UPRTase derived from Escherichia coli was performed as shown below.

 <Preparation of recombinant wild-type UPRTase for crystallization>

 Recombinant wild-type UPRTase used for crystal preparation for X-ray crystal structure analysis was prepared as follows. The reading frame of the upp gene that encodes UPRTase (open re- reading frame) is assumed to start with Met-10, and Cys-160 is expected to be located on the surface of the molecule, causing aggregation when the purified enzyme is concentrated. This was replaced with Ser. In order to amplify the gene region corresponding to the above shape, fusion PCR was performed using the following four types of primers and the wild-type upp gene cloned in plasmid pQE82L (Qiagen) as a mirror type.

 [0 0 8 6]

 PQE_C160S_Nl and pQE—C160S—N2 having the nucleotide sequences represented by SEQ ID NOs: 3 and 4 and pQE_C160S_Cl and pQE—C160S—C2 having the nucleotide sequences represented by SEQ ID NOs: 3 and 3 and 7 were used as primers, respectively. PCR was performed separately and each product was purified by agarose electrophoresis. Subsequently, PCR was performed by mixing them into a cage and using pQE_C160S_Nl and pQE_C160S_C2 as primers. The amplified fragment was digested with the restriction enzyme BamHI, purified by agarose electrophoresis, then previously quenched with the restriction enzyme BamHI, and then ligated with plasmid pQE82L treated with alkaline phosphatase. Escherichia E. coli DH5α strain was transformed. By isolating the plasmid from the transformant and conducting base sequence analysis, it was confirmed that the UPRTase having the amino acid sequence represented by SEQ ID NO: 38 was expressed as a fusion protein having a histidine tag at the amino terminal. did. Using this plasmid, Escherichia coli BL21 strain was transformed, and the obtained transformant was used as the following UPRTase expression strain. Substitution of C160S had little effect on the specific activity of the enzyme (data not shown).

 [0 0 8 7]

250 mL of Terrific medium containing 50 mg / L ampicillin in a 2 L baffled flask (12 g / L tryptone, 24 g / L yeast extract, 9.4 g / L hydrogen phosphate strength, 2.2 g / L After incubating 4 hours / 37 ° C for 4 hours after 0D660 reaches approximately 2.0, the final concentration is reached. IPTG was added to obtain 1 mM, and the cells were further cultured at 25 ° C for 12 hours. The resulting culture is collected by centrifugation, and the precipitated cells are disrupted with a disruption buffer (50 raM Na-phosphate pH 7.0, 300 raM NaCl, 10 mM 2-mercaptoethanol). The cells were disrupted by ultrasonication while being cooled in an ice bath. This was centrifuged at lOOOOrpm for 1 hour to obtain a cell extract in the supernatant. TAL0N resin (Clonetech) was used for purification of the histidine tag fusion protein. 200 / L TAL0N resin was used per 50 mL of culture medium. After washing with washing buffer (50 raM Na-phospha'te pH 7.0, 15 raM imidazole, 10 mM 2-mercaptoethanol), elution buffer (50 mM Na-phosphate pH 7.0, 150 mM imidazole, Elution with 10 mM 2-mercaptoethanol). The above operation was performed at room temperature. The following operations were performed at 4 ° C. The collected fraction was dialyzed against anion chromatography equilibration buffer (20 mM Tris-HCl, pH 8.5) for 1 hour. The dialyzed solution was centrifuged at lOOOOrpm for 10 minutes, and only the supernatant fraction was collected. Added to an anion exchange column (monoQ ram, GE Healthcare Bioscience). After sufficiently equilibrating with the above buffer solution, elution was performed with a linear concentration gradient of 0 → 0.5M NaCl using UV absorption at a wavelength of 280 nm as an index. The active fraction eluted in the range of 250-350 mM NaCl. To this active fraction, a stock solution was added to a concentration of 0.5 mM DTT and 0.5 mM GTP, followed by concentration using ami con ultra-15, and further concentration buffer (20 raM Tris- HCl pH 8.5, 20 mM NaCl, 0.5 mM DTT, 0.5 mM GTP) was added, and the solution was concentrated to a concentration of 18 mg / mL while exchanging the original buffer.

 [0 0 8 8]

<X-ray crystal structure analysis of UPRTase>

Crystallization was performed by a sitting drop vapor diffusion method. The recombinant UPRTase concentrated solution prepared above and a solution containing 0.2 raM di-ammonium tartrate and 15-20% (w / v) PEG3350 are mixed in equal amounts and left to stand for about 1 week. 05 X 0. 05 X 0. 15 About ³ columnar crystals were precipitated.

 [0 0 8 9]

X-ray diffraction data was collected using the Quantum 315 detector manufactured by ADSC at the Beamline BL5A of the Synchrotron Radiation Research Laboratory, Institute for Materials Structure Science, High Energy Accelerator Research Organization. The wavelength was set to 1.0000 A and the distance from the crystal to the detector was set to 352.4 mm. The measurement temperature was 100K. The exposure was performed for 20 seconds at a vibration angle of 1 ° per frame. As a result of processing data using the CCP4 package program Mosflm, the Emerge value was 10.8% at 100-2. 3A resolution, and 2.4.2-2. 3θΑ resolution at the outermost shell was 61.1%. became. The completeness of the data was 92.9 at 100-2.3 A resolution and 99.6% at 2.42-2.30 A resolution of the outermost shell. Crystal belongs to trigonal system, spatial group £ 3 ₂ 21, the lattice constant Dan = 73. LA, c = 279 . 9A, a _ = _ ^ _ = 90. OA, upper = 120. OA der ivy. The asymmetric unit of the crystal contained 4 UPRTase molecules, and the solvent content of the crystal was about 45%.

[0 0 9 0] <Determination of 3D structure>

The structure was determined by a molecular replacement method using the monomer structure of Thermotoga maritima UPRTase (PDB code 1050) as a search model. MolRep (CCP4 package) was used as the structural analysis program, CNX (Accelrys) was used as the structural refinement program, and Coot (CCP4 package) was used as the structural display program. After repetitive refinement work, a refined structure with 2.3 A resolution including water and GTP molecules was determined, and the Rf actor was 21.0% (Rfree 28.3%). When a ramachand lamp lot was created using the program PR0CHECK, 90.6% of the residues other than glycine were located in the most preferred region, and 99.9% of the total residues were acceptable. It has been shown to have a bond dihedral angle.

Table 1 shows the obtained three-dimensional structure information (structure coordinates).

 [0 0 9 1]

 【table 1】

 CRYST1 73. 070 73. 070 279. 920 90. 00 90. 00 120. 00 P 32 2 1

 ATOM 1 CB SER A 9-34. 044 -3. 317 -15. 005 1. 00 66. 85 C

ATOM 2 0G SER A 9 -34. 150 -2. 021 -15. 567 1. 00 67. 98 0

ATOM 3 C SER A 9 -35. 070 -4. 992 -13. 455 1. 00 65. 61 C

ATOM 4 0 SER A 9 -36. 118 -5. 637 -13. 357 1. 00 66. 62 0

ATOM 5 N SER A 9 -34. 847-2. 595 -12. 774 1. 00 66. 45 N

ATOM 6 CA SER A 9 -35. 094 -3. 531 -13. 908 1. 00 66. 28 C

ATOM 7 N MET A 10 -33. 877 -5. 509 -13. 177 1. 00 63. 16 N

ATOM 8 CA MET A 10 -33. 726-6. 907 -12. 790 1 00 60. 56 C

ATOM 9 CB MET A 10 -32. 245 -7. 306 -12. 806 1 00 65. 40 C

ATOM 10 CG MET A 10 -31. 731 -7. 769 one 14. 176 1 00 69. 91 C

ATOM 11 SD MET A 10 -32. 514-9. 303 -14. 784 1 00 75. 03 S

ATOM 12 CE MET A 10 -31. 081 -10. 203 -15. 451 1 00 73. 23 C

ATOM 13 C MET A 10 -34. 332 -7. 197 -11. 419 1 00 56. 40 C

ATOM 14 0 MET A 10 -34. 450-6. 310 -10. 571 1 00 54. 73 0

ATOM 15 N LYS A 11 -34. 711-8. 453 -11. 212 1 00 51. 72 N

ATOM 16 CA LYS A 11 -35. 626 -8. 812 -10. 137 1 00 46. 71 C

ATOM 17 CB LYS A 11 -36. 390 -10. 087 -10. 516 1 00 46. 56 C

ATOM 18 CG LYS A 11 -35. 491 -11. 278 -10. 820 1 00 48. 22 C

ATOM 19 CD LYS A 11 -36. 254 -12. 430 -11. 461 1 00 48 86 C

ATOM 20 CE LYS A 11 -37. 453 -12. 844 -10. 621 1 00 51 11 C

ATOM 21 NZ LYS A 11 -37. 918 -14 228-10. 932 1 00 49 91 N

ATOM 22 C LYS A 11 -34. 953 -8 991 -8. 775 1 00 42 84 C ooooooooooooooooooooo ooooooooooooooo en cn nnn cn en ^ cccccccchhhhsorhr oo --- 1 σ> n -f ^ ho oo --- i o> oi ^ co i oo oo --- 1 σ on -p *. cozoooooozoooooozoooo zoooo ^ o

 C5 o co> rn m σο 5 o co 3 o GO ^

I

 c 3 en

C CO

r oo h po σ¾ oo

 o z o o o o z o o o o z o o o z o o o o z o

LYS A042.47 0 """""""" 一 一 ェ 一 ェ 工 工 工---""-<"-<"-<"-<— — "1 1 1 1 1 1 1 1 1 1

One — ^ — (

 1

 C I I I I I I I I I I I I I I I I I I I I I I 1 I I I I I I I I I I I I I One ^ 4 1

 1 1 1 1 1

 1 «1 1 1 1 1 1

i oo 7 — — 1

o o σο> · i m o σο> · m m σ σ σσ> · h ^ j m o σσ · o — ^ h — * ■ — ^ h

 rn rn rn rn m m m-<-<-<-<-<-<-<-<-<

 CZ CCC CI CCOGOOCG OO OO C GO C CO CO GO — O ―C —C -G -O -O <O -O <-C <-O <-O-<O -G ^ cccccccccoo ho hrrrrr ^ 1 1 1 1 1 1 ooc ho hr rsD 1 1 1 1 >> 1 1 1 h AAA ai oi σ¾ σ¾ σ¾ σ¾ αι σ ^ 1 ο οο οο σ¾ σ¾

-»-J co oo co oo --jc o> o ri ai one c -o oi ho oo oi cnj ^ one-« (^ one OIIIIIIIIIIIIIIII! IIIIIIIIIIIIIIII r one one " ¹ " Nj rrrhrrrhrrr ho ho ohr ro rsD rr ro one r one hrrhho — ^ h oo-^ i 7 o -t ^ -t ^ -p ^ c ^. oo-«j ι · ^ σ οι · ^ ο one co coco one one one one r> co 1 o AA oo * «J Oo oo o¾ co o> ho ho co 1 rsa co oc oi cn ho ci ^^ rc 1 o 1 ^ J en σ —> 1 oi-c― o -¾-o― o- -One ^ r One oo-r One o One> r― -One ^ c '^ One j — ^ o o5 — »-o ^ o rND Oo-^-^ cy rs3 0o o>-^ o — ^ r co

 ≥k '-O One <o ― ο One σ One One One One One — One σ¾ — ^ n co o <oo ^ n is3 h -t ^ oi ι σ¾ cn c ι one oor ro o one cc oo oi ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο

OC --J 00 <r ji o¾ --- irohoo oo o> nrr oo-(^ o> c cji o o¾ — ^ oo oi rsa oo ^ JI — »-00 4 ^ CJ O C0 Cri -J Cn 0> C 00 I CO-^. CO C ^ | —. O iND -J n 3 O¾ <OC 3 4 ^ zozzozzoozozoozo

σ σ> σ> σ> σ> σϊ σ ·^ «ρ*· c c c Ai c c c^ oo o o z o z z z z o o o o ^ o o z o o o s: ATMO

σ σ>σ>σ>σ> σϊ σ · ^ «ρ * · ccc Ai ccc ^ oo oozozzzzoooo ^ oozooos:

 σσ 3 Γ Γπ σ ο οσ> m o c¾ 3 σ o σσ 3 3

 i> o ro — *

 CD C¾ C¾ CT>>> 3>>>>>: »:» SSSSSSSS C¾ C¾ C5 CD i— (— i— i— ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ mmmmmmmmmmmmmmmm i- r ~ i— r " mc <= c = c c5 C75 cr5 c¾ c¾ c¾ cr> c¾ — ii czi (= <= zc: cc: cz-<-<-<-<d

IIIIIIIIIIIIIIIIII f IIIIIIIIIIIIIIIII rrhcrcc AD C cccccrrrrr ro chcccccccnl oo o oo o — *-* -J n oo ro-*-J Co ^k cn oo — ^ — ^ σ¾ σ>

 tO O OO

 o oo co ro oo-^ j — ^ ho o c — ^-^. σ¾ CO o co co A o o oi a o oo o o oo oo

CO CO

 ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ooooooooooooooooooooo oooooooooooooooij oo oo j oo jjn ι oo

• ^ h oo co cc ^ ^ ^ JC ro ^ r OAA Na ccrc oo hr oi o oo c os "-^ ι oo oo co> CJi ho oaoco> o¾ oo o oi 4 ^ h oo 3 --j ho r < o oo ZOZZZ 2E OOOCZOZZO

M ATO 3>·> · 3 * 3>>>>>>>>>>>>>>>>>>> ooooooooooooooooooooo oooooooooooooor ro ho 1 """ ¹ 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

 o o o co co co co o o o o oo oo oo oo oo oo oo oo oo oo ^

 h one o <oo-»J O¾ cri c ho one o co oo --j a¾ cn one o o oo

 0 0 0 0 0 Z 0 0 0 0 0 0 0 0

 CD 3> σ OD ΓΠ

一1 h

one

c c c c c c c c c c c c c c c c c c c h r r r r c c c c c h r r r r h h 一 一 一 ー ー ー 一 一 o o o o o o o o o co co < o CO GO CO GO CO GO OO ― ― 1 1 1 1 1 3 3 3 3> 3 3 3 3 OO C¾ C¾ C5 C¾ C¾ mmmmmm """""""cooooooo"""""""""""""Cccccc

ccccccccccccccccccchr rrrccccchrrrrhh One-one --- One ooooooooo co co <o CO

 o

ooO oo cj o ji

oo

C

 T ^ ^ o> o one [ss ^ jo o co one c co o>-ic — ^ co cc oo to ^ c -j — »-o ^. I ho oo oo-^ o> c — ^ o¾ o¾ n — ^

 ^-^ ー ^

on one <o 4 ^ one one h ~ *> h one joc one ai h oo one n <co> o ho c ^ oo cn one one one one one one one one one one one one one one one one rrrr one one rr ro hr 1 1 1 1 1 1 c ^ ⁰ ; ^-1 ";^;- ¹ ";- ¹ "! ^ ^ ⁰ ^ ⁰ ; ^! ^;- ¹ "! ^;-^ ^ ^ ^; ^ "^ ^ o co one ai oo o DO co i σ¾ one o oo oo yi DO co o ai ^ j oo o>o> o one co co« -jo oi o> coj ^ oo-«i-^ o — ^ onc oo oi — *-oo n oo r --J cD C »noocooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooo en in-^ j" ^ jo ho — »-ooo <ro n <^ ι ^ iooo co — ^ oc — * -cr — ^ o oi oi n ^ — ^ c oo c on o) ^ i ro ¾ »o — ^k no ro o oo oo — ^ ^ i ro js ^ o — *-ο ^ ^ ι ο οο ο ^ ι ο-^ ζ

0 Ο Ο Ο Ζ Ο Ο Ο Ο Ο Ζ 0 0 0 0 0 0 3 Ο Ζ Ζ 0 0 0 2ί Ο Ο Ο

Debate

 h ho 3 io o o o o o o o o o oo 1 σ> en -t ^

O O O O O O O O Z O O Z Z O Z O O O O Z O O Z O O O O C5 Z O O O O O O Z r i rn m o oD 3 Ν Γπ σ ο σσ> m σ c¾ 3 co 3> ro — »■ r — ^ h — ^ h

 "

ェ ェ ί ^ ^: ^; ^

mmmmmmmmm C5 co oo ccccccccccccccccccccr hr Na rh ro rsa rrrr ro hrrrrhrhrr one one one h one one ro co oo oo> o> o> o> rcho — *--^. ri co oo o> o ""-« i

en one oo one I co co en σ¾ — »■ no> ro o> <cn ho> oho co o o¾ o¾ o — ^ ro — * 4 ^ cji n ^ c oi oo ^ — ^ <ooh I — ^ co o ¾ »I-^ 4 ^ co ^ o ^ ι ι ο οο σ> o ∞ one one one srrh ho rrrorrrrrhrr isj cccr ho hrrhorr ho ro oo oo oo ooo DC -tSfc nn o¾ o¾ 1 oo oo oo σ> σ> σ> σ> ι one o co oo in ^ -i ^ crcc one "-^ I OO CO — ^ Ι Γ Γ ^ ΟΊ ΟΊ Ο Ο Ο Ο Γ Γ ΟΟ I OO OOO) ^ 0 ^ J-^ h O 71 00 ^ 0) 0> --JO One ""--ι ο σ> οι co ir on ο σ¾ to io ^ J n «^ ^ l oo r cn oi One *« One σ¾ — '• no-"ih oo to one ^-«ι o"-"« ι one c <orccoo> one oo --- <oor σ¾ oo one o one one o one o one ri AJ ^ A Coc one ro one co o one ho rc one r rsa j ^ cc A c "-j ro one o --joo one" ^> one one ro ^ o¾-^ ι oo σ> oo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooo

^ ro on i rs3 ^ ^ ^ 4 ^ ^ ^ oo ji o rs3 0¾ jn rs3 co ji ^ ^ -j to h ^ joc oo o¾-^. o¾ cn oo <o J1 CJ1 OO 1 00 0¾ 00 DOO 01 0 O 01 --J One O One 01 0¾ 0 0> 0 | \ 0 00 r _ ^ o ^ oozzzozozozoooz:

M ATO ATOM 27ER A 42434 N S23.7823.66.33600.760--

ATOM 2723 ALA A 4124.721.8282 0019.82013.521-

ATOM 272 ALA A 414.22, 476311602282.481 00.6--

ATOMLA AB A23.093 0023.04 C-

ATOM 270LA A 414A A24.40921.939. 0023.08 C906--

AM 2A A 41TO69 N AL24.82122.99854 022.02.810--

AMTO 268 LEU A 4026.70823.42442.460. 003--

ATOM 267 LEU A 402.523.6605. C595607 0023.05 -—

 ATOM 2662 LEU A 402.7. CD28.9205838907 00.30—-

ATOM 2651 LEU A 404424.10. CD28.1693S5 00.04—-

ATOM 26 LEU A 402.28 ・ 4 CG27568665 00.06--

ATOM 263 LEU A 407.424.177. CB2039799 0020.42—-

ATOM 262A LEU A 40.424 7646. C2628592 0011.72—-

ATOM N LEU A 40.772.4427 · 2505036 0023.13—-

ATOM 260 GLU A 394 · 726 · 3335 · 70253024 0025.9 -—

 AM 2TO59 GLU A 394,126.2546 · C23923 002428--

AM 2TO580E2 GLU A 392.26730,659..73303 009--

ATM 257O GLU A 39229.995.2 65478 0035—-

ATOM 256 CD GLU A 3923.93430.so 9.2.5470 0066--

ATOM 255 CG GLU A 3923.20329, 2068.27.25406 00--

ATOM 254 CB GLU A24,29287.U 024.99090--

ATOM 253. CA GLU A 3923.33127.091627 0025.579--

ATOM 2527 N GLU A 392226 0023.34--o z o z o o o z o z z z z o

 ATOM24. ARG A 38245830 0023.201

 ATOM 25025.0946. C ARG A 38.976996 00.79-T AOM 249 N A823.360H2 On ARG 3 4. 0023.38-TOM 24 A8 AR A 3825.9 .. G on 969 002080-

On ATOM 247Z AR A8 24224.2.4 CG 3 0040-

ATOM 246 NE AR A 3829723.75892.57G 003-

On ATOM 245 CD AR A 38 7.32724.8.22.95G 5 00-

ATOM 244.8 CG AR A 3818.64623879.22.25G 4 00--

ATOM 2432.7 CB AR A 38 Over 48823.40G 00-T AOM 242247. CA AR A 3822.89G802 001

M ATO 2411.42.1 N AR A 382623919.23.38G132 001-TM AO 2402.2.70 PHE A 3733802158.24.59384 001— M ATO 23922.72. C PHE A 378532569.23, 70303 00-- >>>>> ooooooooooooooooooooo oooooooooooooooo one o

o o o o z o o o o o z o o o z o o o o o o z o o o o o o o o z o o o o o Uniform s s

 <^

Ichiichi ~

One one one

 One one

1 ' ^1_ ~ 1 1 o 1 1 1 1 1 1 1

. 1 1 1 1 1> 1 1-ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο 一 一 · "-zoozozozooozooo

ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο c c c c c c c c c c c c c c c c c

 ^ 4 ^ ccccccc co ho ho r ho ho ro ho r rv r one to one one one one one one cn n -f ^ cr — ^ c oo-· ■ i cn n -p *> c ro — ^ o oo lo ^ ncr one oc oo r one

O O O O Z O O O O O O O O O O O Z! O O O O O Z O O O O Z O O O m σ σσ> · Ν Γπ σ πι σ ο οσ> 3> o σ σσ-σ one r r one ro — ^ h one ro

O C¾ C5 CD O — I — 1 — I — I — I — I — I — I — I — I — I — t — I — t — I — I — 1 — H -HI ~ l ~ (~ ί ~ Γ "Γ" |-I- I- I- I-

"" "" "" Be "Be Be" ye ye ye ye m m m m m m m m m rn m n n n cn n ai ui n on n n n

 OOOOOOOOOOO O. <O <O <O CO CD CD CO 00 00 00 00 00 00 CX3 CO ^ J -J -J σ¾ οι cch ro one en co J o one ooooo> no> oo oo oo one oo co oo one O --- iw ai ^ r <ooo ri o ^ o ro oo oo o¾ —> 4

oc — * ■ c | S e ^ n S ^ po ^ ³ -H i " ¹ :!" ^

oo o ^ ³ -"^ ⁰ " ¹

CO t IIIIIII t III t IIIIIIIIIIIIIIIIIIII 1 II 00 o One oo One hr-«en> ri ai ^ --- l ai Oi A c One ro One ro One One o cn oi h οο <σ> σ αι οο αι οο οο One O o cn o One o> ai o One r oo ^ i ji ho o ro-* J 3 — ^ r ^ o oo oo — * oo <o ^ i cn oo cr co — '■ cnc ^ ooh oo ooocoo ι — »· <c σ¾-• ^ jccc an ^ id — 3> i o ^ J ho i ^ j to oo co oo hoho

^ j oi o oi ri c oo a¾ oo co — ^ σ> — * * ^ <ο ο ρ ^ <ο ο-^ — ^ ο οο σ> οο σ n ^ ι ^ — ^ cn σ> ooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooo ro ho cccrcccrrhhrhhrrrhr 1 h ~ * "r D hrrh 1 1 ^ I an hi <ro ^. oo — ^t rh o> ^ cor r oo" * j o¾ or cji — *-oo oo o> ri r ^ ι ^ o> ^ -JO ^ J o> oo o — * oo oo oo -P *. r oo --- i ^ n one co rcc ι o 1 oo one ocn

OZ 0 0 0 0 0 0 0 0 2 = OOOOZ 0 0 0 2: 0 0

ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο C CJ C C C C C C C C C C C

 oo oo oo-«« io> o> o> o¾ o> o> o a¾ crt Ji ji ji cn cji n ri ji ji n ^ ooooozoooooozoooo ^ ooooozoooozoooo οσ ooo σσ c> c>> σο ϊ> m ro — »· hr ">>>>>>>>>>>>> ~ l ~ l ~ l ~ l ~ l ~ l>>>>> cr> C¾ C3 mm rn mmmmmcccooooc ai cn cn ri nnn cn cn cn cri cn oi cri ai an ji Ti ai n ji cn ai cn nn oi cn ji oi ai n oi cri ji ji ji o> o¾ 05 0¾ CT o¾ o> ai n oi nn ji ji cccc co co co rhor

IIII t IIIIIIIIII t IIIIIIIIIIIIII t I t ro hhhrhcccccccccc ho hhrc ho cr cj ccc σ> σ> ^ l oo oo O — ^ ohhcccroo ^ J oo oooo to o — »· ο 3 σ> no> cji <ococo — 'θ σ¾ ϋΐ απ ο σ¾ οο 1 oo oo-«jo —-"-i rs3 nc * -jo> ^ r ^ oo ro oo

CO I l I I I I I t I I I I I I I I I I I I I I I I I I I

 fs r — ^

CO o o o o o oo co o o O O h o

co¾ <o oo oo • pfc ho co cno

c

I I I I I I I t I I I! I I I I I I I I I I I I I I I I I I I I I I I I

 c <ο σ en 0 oo co i o¾ n o¾ o¾ o¾ ji o> ji ccc ^ c — *-rr «o — ^ o oo o oo o cn —»-cor> o¾ o¾ C7i roo> oo cji — »- Γ> ο οο ο οο ^ ^ ^ Γ αΊ Γ 1 to oo ooc cj5 ^. C cn c »oo cD T5 — ^ o oo ^ — ir — ^ on <0 4 ^ oo cr> co j¾ ^ o ri cn- -1 o oo cn ~-CT> ir ^ co oo ^ — ^ o-^ j ro ^ ji — »-i oo ho-^ oo j5 *« J 3 C ^ J oo ι o cn ^ co co ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooo co a) -f ^> oo l oo os cn n — ^ oo oo o ^ cn choo ^ i to ^ j ^ j o¾ o¾ o> h o¾

 on 1 o n r "-1 —-^ co — ^ n oo o o oo cn o r T> c o ji-^ an — ^

ooooozoooooozoooozooo zooozoo

 ^ 4 ^ 4 ^ 4 ^ 4 ^ 4 ^.

 o o o o o o o o oo

 c r one

o z o o z o o o o o z o o o o o z o o o o ^ o o o o z

> N ΓΠ C7 C "> CD> ΓΠ ΓΠ CD J * C" 5 C "> DO> ΓΠ ΓΠ ϋ CD CO 3> ro ro i r —» ■

 「「 「「 「「 「「 「「

 「「 「「 「「 「「 「

—>-—>-O o o o o o o o o co o c co oo oo oo oo oo oo oo

I I I I I I I I t t I I I I I I I I I I I I I I I I I I I I I I I I I ro ro

 > o σ¾ h r — »■ <oo oo-1 i r c cri n ** j ^ J Oo oo cD O c oo c ^ J Oo o> o> o> a¾ oo <oo

^ cji oo o ri cnrror -i ^ to n · "-iro ^ i c --j i oo ncorcno co o co i rvj oo ro co oo i-i co ai c i co c —> · ^ ϋ αΐ ϋΊ σ¾ σ> one co co (c oi oo ri oooco ^ c one rvo rcj ^ orr a¾ o oo oo cn oi o oo oo one ji co o oo one n-^ r ""-«ic one σ¾ one o¾ n oo ho <Iichi ^ j ji cc ho ho i i ci> oncchn i

! IIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIII oo oo co oo cj> i oo <o oo ^ j o¾ o οι σ> σ σ> · ^ ϋΐ one chrh one one • ^ pc rva h one oo o¾-* j-^ oo co c — 1 ai σ¾ --- iro> i> oo — ^ ^ o -P ^ no ai ^ o -J co-^ ji oo oo j ^-ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooonn cn oi cn n ji oi i cri σ σ> σ> ^> ^ · ^ ^ · (^ Ο ~ * · ο one-"-J Oi AJ ^ r one oo hcj \ 3 0o jv3 0 o ^ -jp> ch ri ai ro> o> nr o¾ c one n cn 00 5 C --JOO ^ one coo one oc cTi one oo co ro one an o ~ * 4 ^ a¾ po oo ro σ> ςο σ> οο σ> one c one ο σ> one cn c one one cco oo onooo-» j cn ho oco One O h A roc ZOZOOOZOOOOOOOZ! OOOZOOOOOOZ

謹

 ^ ^ 4 ^ ^ 4 ^ <^ ^ ^ ^ ^> ^ ^> <^ ^ ^> ο ζ ο ο ο ζ ο ο ο ο ο ο ζ ο ο ο ο ο ο ^ ο ο ο ο ζ ο ο ο ο

CO ^> ΓΠ ΓΠ CO ^ ^ α ΌΟ ΌΟ CD

~ I "-1-Ι Ω Ω ^ Ω Ω Every one one-one one ~ I ~ I ~ I ~ I ~ I ~ I ~! <<<<<

; "厂" "" "" "" "" "" "" "" "" ""-"" ~~ ""-~~~ "cc = c : cc: c cz c = = mmm rn mmmm ； ^ ^: ^; σ: = ο = σ "" "" "> ¾

a¾ a¾ a n an n an> ^ c c c c c c c oo r r r h r r ro h ro ro ro ro ro ro N3 r ro

 i o) o> ^ Ji cj> cn c _ ^ c co c r h c c an c ro co c c 4 ^ oi o> 7i ui a> n c ^> co -p ^ cn

oi o oi oo r oo o^ O CO oo n ςο ri ri --Jo> ι co cn co o

oi o oi oo r oo o

I I I I I I I I I I I I I I I I I I I I I I I

co -P¾> cn CJ n n i cji oi o o o co o oo oo ^ oo ^ ^ o ^ oi oo oo o co — ^ — ^ o o --- 1 oo σ> "-1

-«J one • ^ oo oo o ^ o to oo ai r one σ¾ Γοone an ai o"-i o »oo cj¾ <o o cji o --j oo r> co n-^ o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

Z O ^ O O O O Z O O Z 0 0 0 0 0 0 2T O

basket >>>>>>>>>>> ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο ο ^ ^^ ^ 4 ^ J ^ AAA ^> * ^ ^> 4 ^ ooozoooooos: oooz: oozooozooooozooo CO D> DO O σ OD 3 Ν Ν ΓΠ σ ΓΠ ΓΠ σ θ

 ~ D "0 -D T3" D "D" D C¾ C C CD 3 3> 3 3 3 '3>' '— I — I — l -H — I — ί — I — I — 1 — 1 — (

-—J · — j j j j jo) σ> o> σ>> σ¾ σ¾ σ¾ σ¾ σ¾ ο¾ ο¾ ο¾ ο¾ σ¾ ¾ο σ¾ σ¾ σ¾ ο¾ ¾> σ¾ σ¾

IIIIII f IIIIIIII 1 IIIIIIIIII, I t IIIIIIII oo co o to oo co ι σ σ¾ σ>σ> σ¾ σ¾ σ> σ¾ "-<ο οο θ Γ * — ^t O oo oo o¾-* j —-- oh — »-* · <Ο οο σ> ^ I ro ^ loo —» · σ> — »· σ¾ — * ·»-o -p *. O oo σ οο <ο αι ο ο i o oo coo oo oo oo < o σ> co oo ■ "-oo — ^ n ο σ>

 IO OO OO CO OO ^ O ^ D 3 3 C ^ T1 0¾ 0¾ J1 0> 0 --J ^ J O¾ 00-*-JO tD OO O> 0 D --- 1 -J σ> oo σ> oo ^ r> o σ> ^ i co oo nc co oo un ji oo ^ no-^-^ oo co o ^ ^ loo oo ncoc one co> ο σ> ι ι co ^ c co co ro co ho —

IIIIIII 1 IIII 1 IIIIIIIIII f IIIIIIIIIIII rsD orrrrcccccccccchcrrrr ro rrhrrphhhr ro hr oo σ i oo ooocr-* ho-»-oo ooo co ^ J Oo oo oo oo o¾ a¾ o¾ ri ri ^ co c ai ^ ^ co o> ai" «J oo 00 3 o ji one to one" ^ hcn co — ^ o — *-cn hr ^ o ji o rs3 Ai oo

o> croc co ^ o — ^ to -j oo oo h ho oo o • ^ j 4 ^> ^ i on ϋΐ σ¾ <ο <ο σ¾ ϋΐ oo oo O OO hO h0 ^ 00 00 0) 0) <OC 7> 00 — ^ O>-J CO ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooo 01 oi oi n ji n ai ji ji on n ai oi oi cn o>o> o¾ o¾ cji n ai n ai cn oi ci oo oo oo t — »■ —»-o> o¾ ji o¾ * «-J Oo oo ^ i oo oo-^>^> ro oo co oo ji 7i ^. a) ^ j ^. cn no) rcr --o ^ 00 01 01 One <o One "^ hc One ^ j ^ jo oo oo ri * -j One co o — *"<0<0 0¾-»^ rcoocc-^ j oo c oo rhoh co oo co on- -One ^ ""--co ozoooozoozozoozozo

ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο s s s s ≡ s s s s s s s s s s s s s s

 1 ^ 1 1 1 1 1 n ^ 4 ^ ^ oo c c o o r r r r r r

One one one —

 One

 One one one

I I I I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 3 1 «·; 3 οο σο οο

 1 1 1 1

<^ <^ <^> ^>> ^> ^> ^>

 1 1 1 1 1 1 1 1 4 ^

1 ^ 1 c en oc 1 1

〗

 Up

 Up

 Up

 丄

丄 丄 丄 丄 一 一 一 一 一 一 一 一 一 一 一 一 一 一 一 一 一

一 丄 丄 丄 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

 1 1 ^ 1 1 1 << 1

 One << one 謹

 .

Up

 丄

 丄

 Top

丄

 Up

Up up up 0 SS ZZ 00 I ε- £ 90 • Ll- S8fr 'S n V Odd 00 869 W01V

0 30 ZZ 00 I 'τ-s 91- 09fr • 91- n V Odd 90 O 6S WI01V

0 36 ZZ 00 l εοοε-968 "5 L- 631 l- n V Odd VO 969 W01V

0 SS ZZ 00 l 0L8 m • 91- I I I '91-V Odd αο 969 ■ V

N ZZ 00 i V- 0L9 "91- ZIO L l- n V Odd N 176 1 / IIOiV

0 IZ "93 00 I 966 'G 606 τι- S • 8 L- 98 V ΐνΛ 0 G69 I / IIOIV

0 36 ZZ 00 L εε '9- 09 O n- 909 a- S8 V 1VA 0 36S I / IIOIV

0 09 ZZ 00 l 680 • 6-6 ι- OS a- S8 V 1VA 2D0 169 麵

0 0 '6 L 00 L B-339 369 • 91- S8 V 1VA 069 W01V

0 9C ZZ 00 • I 909 B-ζι- • Ll- 88 V 1VA ao 689 隱

0 OS ZZ 00 l ■ 9-996 n- 633 Ll- £ 8 V HVA VO 889 ■ V

N SZ 00 l οιε B-LLQ • 91- B 86 Ll- £ 8 V ΠΥΛ N ■ V

0 179 LZ 00 l 9 ^ 6 B-ZZZ Ll- 191 91- 28 V 1VA 0 989 INOIV

0 99 Ll 00 l 106 L- 860 Ll- m Ll- 38 V UK 0 989V

0 Ll ZZ 00 l • 8-LZ9 oz- 688 • 8 G 28 V 1VA 390 INOIV

0 8fr 83 00 L see '9-III • 61-60 B • 8 G 38 V 1VA L90 C89 WOIV

0 817 LZ 00 L w L- 6 61- L i • 8 G 38 V UK ao 289 mioiv

0 83 00 L • 8-S l 81- 963 • 8 G 38 V UK VO 189 WOIV

N IZ 00 l 216 ∎6-118 ∎81-CC6 ΊΛ- 38 V 1VA N 089 WO 丄 V

0 B S 83 00I S B 9 01- 098 '91-9 ^ 61- 18 V i 0 6 WOIV

0 01 6Z 00 l 6 B 8 01- B l-• 81- 18 V dHl 0 8 WOIV

0 89 6Z 00 I εο9 U- 90S • 91- L91 • 91-18 V yHi 390 LLS WOIV

0 U ZZ 00 I 916 ΖΙ-908 • 91- S39 • 91-18 V dHl 190 9 ■ V

0 S9 6Z 00 I 699 Ζ [-869 • 91- 86 L ΊΛ-18 V ¾JH 丄 ao WOIV

0 £ 6 '83 00 l 183 '-S98 Ll- 666 Ll- 18 V ¾JH 丄 VO ^ 9 隱

N 08 9Z 00 I Z9Z ε ι- 903 ∎81- no • 61-18 V ^ 丄 N ε S WOIV

0 n "83 00 I 386 'ε ι-010 03- 06 L l- 08 V 311 0 ZL WOIV

0 19 LZ 00 • I 900 • w-ζοε • 61-916 • 81-08 V, 1 0 9 WOIV

0 99 LZ 00 "l 89" 91- 9 oz- 096 zz- 08 V 311 LOO 0L9 WOIV

0 91 LZ 00 l 391 "91- ΛΖ- 930 11- 08 V 3, l 190 699 I / IIOIV

0 10 LZ 00 l 196 ζι- ^ 60 02- 909 ΛΖ- 08 V 3Ί 390 390 899 WO 丄 V

0 9B 9Z 00 l ζοζ η-60 QZ- 996 02- 08 V 311 ao B 9S WOIV

0 89 82 00 l η- 899 • 61- 380 02- 08 V 311 VO 999 WOIV

N ZZ 63 00 l on ■ 91- m oz- L09 ■ 6 G 08 V 311 N 999 WOIV

0 91 00 l ILV L l- ■ 81- 266 • 61-6 6 V S person 99 0 99 WOIV

0 99 OZ 00 I 9LZ a- 91 ^ 9 • 61— OOfr '61 -6 V SAT 0 G99 WOIV C00 / .00Zai / X3d 6 8 £ 0 / 800Z OAV

OZOZOZ 2E ZOOOZOOOS: OOOS: O

ο) ο

7> l oo c — »- o n c ro — *· ο ο ο οο οο ι ι r c σ> o oo 1 o o σ> o o o o

7> l oo c — »-onc ro — * · ο ο οο οο ι ι rc σ> o oo 1 oo σ> oooo

 o <oo σ¾ o o OS o <y> o ro o oo o oo o h o oo o

 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 r ro ro ro ti ro t ro ro ro ro ro fi

o¾ n <j> n cn ro ro o oo o o o o O <o CO CO oo oo oo σ> to o o o o oo oo ro cn

 oo h o σ¾ ro oo σ> o oo o oo o oo o o σ> OO σ> cn h oo o o o O o oo h

 1 1 1 1 1 1 1 1 1 1 1 1

ooo ro ro O CO ro ro 丄 oo one oo ro ro one o one ro one one ooo oo oo <y> O o ∞ on CO o CO o oo oo oo cn cn oo oo o ro ro oo σσ ro oo cn oooo oo oo o σ> σ> oo O oooooooo O oo O oooooooooooooooooo oooooooooo ooooooooooooooooor ro oh ro ro ro ro ro ro ro ro ro ro ro ro h ro h ro ro ro rr ro ro CO ro ro ho oo σ> <y > o cn σ> ro oo σ> o ro o ho ro oo ro oo oo oo ooo σ¾ oon σ> σ n cn o

o o o z o z o o z o o z o o o o z o

ATOMLY A 89 0 G

ATOMLY A 8 C G9

 ¾>> o>> o>>> CT> o> ¾>

 o¾ n h o o oo> oi 4 ^ c ro co oo ι σ¾ n ^ ro — »· o -P *. CO hO

Z O O O O Z O O O O O O O O Z O O O O O O O Z O O O O O CD Z O O O Z O C5 σ ϋ c¾ m m ϋ σ σ o σσ c¾ σο?>

 h h — ^ ro ho — ^

 >>>>>> C¾ C¾ C5 C C¾ C¾ C5 C¾ C¾ Ω

 GO 3 GO CO CO GO I ~ I ~ I ~ I ~ I ~ I ~ I ~ Γ ~ ΓΠ ΓΠ ΓΠ ΓΠ Γπ ΓΠ ΓΠ m

 ---<-<-a -o <o

<

 I

oo n

 cn

i

 IIIIIIIIIIIII t IIIIIIIIIIIIIIIIIII n-^ i — I oo oo ^ — II icccn ji oo n σ¾ σ¾ ι ρ¾ ρ¾; ^ j cn nj ^ j ^ orcrcoo <o — ^ o oo ""--l oo o oi c ^ -j ^ -j co cn — ^ o oi oo no oi c oi ^-»ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ooooooooooooooooooooo ooooooooooooooo co co noo --J --J r ri o> T> ^ c co oj> 0 "> chccj ^ cn c-« ι ^ oo co σ¾ oo -t ^

ζ ο ο ζ: ο ο ο ο ο ο ζ ο ο ο ζ ο ο ο ζ ο ο ζ ο

o o o o o o o o o o^ c c c c c c oo c c ro ro r h r h r o o o z z o z o o o o z o o o o z o o o o o z o o o o cs z o o o o o o z o o N rn C7 0 0D > 0D > CD CD 3 CD · C¾ C3 0D > ATOM ooooooooooooooooooooo ooooo

oooooooooo ^ cccccc oo cc ro ro rhrhrooozzozoooozoooo zooooozoooo cs zoooooozoo N rn C7 0 0D>0D> CD CD 3 CD · C¾ C3 0D>

h — * ho

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o co c

 C C C C C r o o o o o o o co ho h r h ho n ro ^ o o

oi Oi ^ F ^ oJ o oi c oo o5 A o¾-»j o¾ ro n ~ *" 0 <0 ^ j> * »j« ^ o ji

IIIIIIIII ttt IIIIIIIIIII l IIIIIIIIIII Iji o¾ o¾ --j oo coocrc "P ^" f ^ c oo "-» JO>"-j --- 1 ot oo oo 1 oi ^-^. Σ 1 \ ro rc on 00 ro n-1 nc ""--1 i ^ j co ^ oo ^ to cj cji oi oo ^ oo -jn -i ^ n os oo r ^ os — ¹ o ^ "-l oo h --- ij ^ o¾ hc co 0 h ai oo o> cn co oo co ~ ^ r --jno ji oor ~ ^ nccoo oo c ο hr cn oo o O hc T o> ro nrc "» j cn o> oo c o¾ co ~ c ^ j ^ oo ji ^ j-»j cy> c ji c cn oi <ocrr" ^ 3 0o o> ooo ^ J ho oooo tn oo ^ oo oo> oo oo h 00 co oi n oo oi oi nr 00 00 οο ~ »· ■ ι co σ to co cri o — ^ oo oi —»-n -i ^ c — ^ — o — '■ co — ^ c — ^ ho o ^ ihr co ooooooooooooooooooooo oooooooooooooooo 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 io <-»jc ji 'c co cTs oi o ^ -j ji rhcrf fsa o ^ to en o σ>σ> οο — ^ co — »-<^ c --jrc rsj cji ai o ι ο or o¾ ai o¾ σ¾ οο co 1 co o oo o σ) co σ 1 ic ^ ooh oo <oo-« jr oo o-^ oo ooo-^ J Ji 3 cn -i ^ co ji — *-co oo -P ^

ζ: ζ ^ ζ ζ: ο ο ζ σ ο ζ ο ζ σ

z o z o o z z o o o o z o o o z o

zozoozzoooozooozo

>>>>>>>>>>>>>>>>>>>>>>> o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o s s s s s s s s s s

 00 00 00 00 00 00 00 00 00 00 00 00 1 1 1

 — ^ O O O O O O O O O <O <O O O O-* J z o o o z o z z z o z o o o o z o o σ o c¾ ro ■: N m c3 C¾ cn: r σ m σ ro ■ m σ oo r one o one h h one

 s s s s s s m rn rn rn m m> c c o o o o o o

I one I

oo co oo on cco) c one co <oo oo no) co one h — ^t ro ro <oh o¾ oo oo oo o-1 co on

ϋΐ 1 1 1 1 1 1 1 1 IIIIIIIIII 1 1 I 1 1 1 1 1 I 1 II> II One O One oooo rvo One nc ^ isj jLn i CJi Ln ai e an One rs o co ji t co o oi r cn cn oio --J oo ^ --j-^ o> a cji CA ^ c 7) — 1 σ> co σ> en σ> σ¾ one ^ ic co oo one one-one ^ ho one ι oo on co- -1 en c an σ¾ j ^.

(s oo one oo a¾ ji ^ rc -JO one oi n oo cj ji ro rN3 0 one o¾ o¾ ch co one oo <o oo-»J 4 ^ h --- 1 ^ σ) — ^ ro --- i co oo-^ co o — '■ co-^ j ^ -i ^ D Oo ^-^ oo c on r i on ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo oooooooo

 ^ i ^ ^ o> oo> o> o> o> o¾ o¾ o> o> o> oi i ji ji ji ji ji n ri oi oi cji cji ^ ^ ^ ^-^. ^ ^ ー ； ^ ； ^ ^ ";! ^. ^; ^ ^! ^) ^ ^) ^ ^ ^^ coo cri co oo r-^ on oi r oo ri — ^ ι σ¾ αι one n o¾ o cji cn c o¾ o co c σ¾ One oo ^ c <ro ch oi -f ^ rs3 0 -f ^ "-J oo> — * ■ ι One o One <οο ο σ¾ σ¾ σ> One a¾ to o

ο ζ ο ζ ο ζ ζ ζ ζ ο ο ο ό ζ ο

o GO

o co ^ n n oo co oo i o¾ n o¾ cri r ~^ c i i p¾ jji j\3 c j^ j^ ro h ro o c ^ oo ^. cji o o> — ^t ^j oo o r o oo oo ^j ^j oo i^s cn -p^ oo o> o rs3 ^j o ^ r — »■ en en -i^ — * n co ""- - i cn o r o < ro n oo 3 0o oo ^ ^ ^ c oo oo o oo — -- ^j o o rs3 0o 一 r ro r oi >f^ c c 一 r ro o 一 r D C*3 c oi ^J 05 0¾ cn ji o¾ o¾ 一 一 ο ο οο σ> σ> oo - 1 <o ¾o 一 o¾ o¾ oo n c c — »■ 一 一 ■ ^ 一 oo 一 co c 一 h oo o¾ o o 0 "P*> o ro o co o i c co — ^ — ^ — ^ 4^ o n r n n n o j3 --J n h ^— i c ^ n "-j cn n oo o n c — ^ n r o> CA3 C c ai «^ o ji o ai ^-j ^j r a¾ oi r ^J Oi r <o *»J oo ー 一 一 o - O5 o

o co ^ nn oo co oo i o¾ n o¾ cri r ~ ^ cii p¾ jji j \ 3 cj ^ j ^ ro h ro oc ^ oo ^. cji o o> — ^t ^ j oo oro oo oo ^ j ^ j oo i ^s cn -p ^ oo o> o rs3 ^ jo ^ r — »■ en en -i ^ — * n co""--i cn oro <ro n oo 3 0o oo ^ ^ ^ c oo oo o oo —- -^ joo rs3 0o one r ro r oi> f ^ cc one r ro o one r DC * 3 c oi ^ J 05 0¾ cn ji o¾ o¾ one ο ο οο σ>σ> oo-1 <o ¾o one o¾ o¾ oo ncc — »■ one one ■ ^ one oo one co c one h oo o¾ oo 0" P *> o ro o co oic co — ^ — ^ — ^ 4 ^ onrnnno j3 --J nh ^ — ic ^ n "-j cn n oo onc — ^ nr o> CA3 C c ai« ^ o ji o ai ^ -j ^ jr a¾ oi r ^ J Oi r <o * »J oo ー one o-

0 O O O O O 0 O O 0 0 0 0 0 0 0 0 0 0 0 0 0 O O O 0 0 0 0 0 O 0 0 O 0 o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

j5 7¾ an z o o o o o o z o o o o z o o o o z o o o o z o -»J σ¾ co cc co

j5 7¾ an zoooooozoooozoooozooo ozo

ATMO ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ oo oo co oo oo oo oo oo oo oo oo oo oo oo oo oo oo co oo oo co co co oo oo oo co oo oo co co oo oo oo oo oo 00 00 00 00 00 C0 00 --J --J --- 1 i-"j-" j ^ jo> o > o¾ o> a¾ crt a¾ o c7> o cn nn ai cn ninnc> cn -F ^ cr — ^ co -— i cn n -P ^ cr — ^ oc --- io cn-^ ro — ^ o <o oo --j o¾ cn-^ r — »■ oooooozoooozoooo ^ ozooooom σ m c¾ co 3> σσ ϊ σ oo ro 3 3 * rn m

 r one r one h

"<~ <~ <~ <" <What? O ^ 0: ¾; 0? 0>: 1> ">>>; 0 ^ 0? 0; ^; 0 70" "" "" ""

^ σ? σ; Ό; ^ = Ό: = ο; σ; 33 θ θ ο ο ο ο ο '' '' 'oooooooccccccchocho io hrhr> rN3 r ho ho ho ho 3 N3 ho or ro ro r> 1 1 1 1 1 1 1 1

rr ho rrrrh — * — ^ — ^l — ^ ooooooo to oo oo co

 t I 1 t I I I I I I I I I I I I I I I I t 1 I I I I I

c oo --- ι σ¾ «-σ σ σ-^ 4 ^ € ^ 4 ^ Γ οο οο Γ ο ο ο — *-o o o o —

or co i ο σ> 3 · ^ ~ * · ^ ο αι ο i cji ho oo oi o cn co i 1 co co --- 1 ho o co co 4 ^ (--jor ^ — ^ ho ^ "*" One h oo o ji con oi one one inni oo oo rsj h one — »■ cr co co oo o ^ jo" ^ "-jc on oorr o¾ oo o one crno one ¾ one one cc oo oo one ho ooooooooooooooooooooo ooooooooocc co cnnnnn on n cn a5 a> o¾ 7> TJ

 ^ co r co n ^ ι o co c l os n oo ^ j h; — »

oo c co co o one o --J i -JO O5 0o oo oco co one r cn oi oo one o one one chhj ^ <o cj o

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o <o o <c o <o oo oo oo oo oo oo oo oo oo oo oo oo co h o h

h — ^ o oo i o¾ cri -p ». co ro — ^ o <o

 2: O Z C5 0 Z O ^ O Z O Z O O

DD> si in o en> · m m σ on D N m m o o c¾ OT> N

 ro ro one

 "" "" "" "" C¾ cc ^ CTi C ^ c ^ C -σ ~ Ό -α -σ "α" Ό -σ -σ -ο -H — I — I mmm ~ <~ <~ <~ <"Be ~ <Be-<" "" "" "" "" "" "" "" ""

 cz ci o o oo o o o c G c z z z z z z z z z m m m m m m rn m m m rn o o> o¾ cn n n ji i co o c co c c c c r

-"Four

n■ t ^ o ro co ^ j σ> «* j oo σ¾ cn σ> co cx) oo r --j one r one οο ^

n

¾ο o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o ο ~»· < ο οο ο 一 h h oo po po ；^ ；^ ^ ；—^ ；—^ ；^ ^ ^！ I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 I 1 II 1 III III co o 1 rN o oi Oi ai j ^ ho hrcc ^ r i o oo o oo o oo io o co oo oo oo c ^ oo o> cc-«j ro c-» J 4 ^ mr one ro one co ronco one o co cr one on "» »joocj ^ oo one one one one one one one 1 II II III III III III 1 1 1 I 1 III 1 III to o

¾ο ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooo ο ~ »· <ο οο ο hh oo po po; ^; ^ ^; — ^; — ^; ^ ^ ^!

oo J ^ co co co ji ro — »-c — ^ or —»-oo> ooooooj ^ c ri oo oo oo oo o¾ ^ ι an ro oo σ¾ CT ho o oo o ro c one-"J Co o¾ cn r o¾ cO "-J Ji o¾ ^ co σ> o ι ^ c""--co co co -F ^ o cn zoo sr ooooozoozoooozooooooz oooo

 <c <o co oooc <<c co co <cooo <c cn n ji in ai nn cn cccccccro ho or ro o oo i crj n -c ^ r — ^ oc oo --- i o¾ ri ^ c oo-»jo> oi ichi oo oo ^ ι σ> on 4 ^ c

O Z 0 2: 0 2i O O Z O O O Z O Z O

 > σ c¾ c¾ σσ! ^ * o o o co> c¾ co ^

¾>. ― ― 1 1 1 1 1>-> 3 3> 3 3 · Ο € Λ 0 Ο Ο Ο "" "" oo I "~ I- I ~ ~ I ~ I ~ I ~ I ~ occc G oc G m rn rn mmm ΓΠ ΓΠ ΓΠ ΓΠ ΓΠ 一-^ ooooooooc co <ooc <oo oo oo oo oo oo oo "" j "* j-» -ί ^ ι * · »» ι · ^ ι σ> σ σ¾ σ¾ σ>

I I I

 Ichi I (I I I I I I I

1 1 1 1 1 1 _ 1 1 1 1 1 1 1 1 1 1 I I 1 I I I

o¾ oi "-J 05 CJi cj ai" ^ ri O5 n oi «^ ri 4 ^ c r r o one o o co

h o¾ r> c o — »-cri ri <o oo n-^ ho o n --- 4 ^

 r ― ^ n oo σ> c σ> ~~ · ■ "-^ <n ro ― '-p --- i r-^ o¾ oo o co 3 — *-

^. ^. n c oo ^ j oo r co

I 丄 I 丄 I I

 ^ do L 1 1 1 1 1 oo 1 ^ j 1 oi cn oo one oi co oo os hhorc one oo> o oi to one cn _p ^ c "* j oo oo or rs3 ho hh rsD or one one one one one 1 1 1 1 1 1 1 1 1 1 1 1

 One

oo <to cn rc ^ ji ^ t one hh one ^ JOO one << ^ οο οο Α ^-Γ oo oo cn one · >>-θ c one oo o¾ c one h ^ J ho> oo cr A ^ jr 1 ο 1 cn o¾ c o5 0i o o¾ oc o¾ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο oo oo oo oo oooooo ooooooooooooooo

 0 ^ _ ^> ^ <^ <^ <^ 4 ^ * ^ ~ ^ 4 ^> 0 0 0 00 01

O Z O O O O O Si O O Z O O O O Z O O O O Z O Z O O O O

AMTO ooooooooooooooo

 ATOM O CO CO tO CD CO CO CD COo o co hiding o co co oo oo oo oo oo oo oo oo oo <> o> o> o> ¾> r> n ^ r i oo co σ> n ^ C ro — ^ o one o

 > AM rTOn σ o co 3 zc Ν Γπ σ £> σα> m m σ. Ca> ■ σ σ οσ

 h one r one h one

h h ro r o h rND 一 一 一 一 一 一 E mmm M ATOm mmmm iu 「「 「「 「「 「「 cc co occ on ri

hh ro roh rND 1 1 1 1 1 1 E

h o h r r h r r rsa r r h r h r r r r ho 1 1 1 1 1 1 1 1 1 1

1 1 o 1 lj ^ co o ho corhh co hr 1 1 oo c σ¾ αι on oo I —> ■ oo ^-<oo --- 1 o — »· cn <o ji o I on one l oo ror —- · ^ Oi o -t ^ ji oo rsD ^ o¾ oo o — * ^ "-^ i-^-* JOOO o> ch co co« -jr ji o — ¹ 1 1 1 1 1 1 1 rrr 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ~ ... j ^ ^ ^ ^ CT> cio c>> ^ -C ^ c — ^ oc)-^ — ^ rrrr oo oo ^ in — — jcoc oo r cn oo oo j ^ oo OA r cn oo cn o Na co j ^ one-one one oc ι σ> c

 1

1 1 1 1 1 1 1 1 ~ * 1 1 hh ho hro 1 "1 1 1 1 1 1 1 1 rrrh ro J ho rc ^ n oj cnn o> oo co c cn cc ~ ^ ~ ^ cj> ji cn ¾ ^ ~ jj> j rcrj ^ jj c ^ -P ^ O no ro TJ Oo — ^ ooo — ι — — ι — ^ — i fNO Oo ^ ^ ri>-^ — ^ n rs co o — ^k -C ^ co l oi oo hn — ^ oo ji cro ro ci a¾ nnno -t ^. crco — ^ oo cc — ι — »· cr cn co o <oc one""jn oi oco one c ro rr one oo ^ J trrr One ^ j co r one co-«J Ji O hc 4 ^ ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooo

^ O ^ oo o> c c ^ o¾ ji ji o <o o <j> c <o¾ o> ^ r c c r ^ rsj co ^ ^ ts3 ^ ^

ZOGZOS! ZOZZOOOZOOO

o o o o o o o o o o o o o o o o o o o o o o o o o o, o o o o o o o o o o

z o o o o o z o o o o z o o o o o o z o o o o z o o

zooooozoooozoooooozoo oozoo

oo

Ο Ζ Ζ Ο Ο Ο Ο Ο Ο Ϊ 2Ϊ Ο Ο Ο Ο Ο Ο Ο Ο Ο 0 Ο Ζ Ο Ο Ο Ο Ο Ο

 _ ». 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 OOOCC (OOO CO CO CO CO OO OO OO OO OO OO OO OO OO OO 1 · — I ^ II 1 ^ I ^ — I CD T5 J5 oooozoooozooooooozooo ooozo cs ooozooozo CD ϊ CD> O C73 CD DO> £ 5 £ 5 CD> 00 J

 ho r

 -H — I — I — I — Ι ϊ 3> 3> 3>> · ― 1 1 1 1 1 1 C C <C <<<«=: O O O C G C C¾

 >>>>>: t> m m rn m m m

O O O O O tO tO tO O CO CO O O OO OO OO OO OO OO OO ^ ^ ^ ^ ^ --- J CJ¾ 0> 0> 0> CTl

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

 ho h ho ho ho rrrrrrhrrr ~> * rrrr ho -j I oo oo σ) i ^ oo to oo-^ ch — »· ο — *-rch — *-o oo to oo co co o <oo — *-rh co cr DO n ~ -J r> co cn oc rvo oo oo nrr c7i co an ai "-j oo cj5 0 σ> σ> ^ ro an o <oO IIII

 o o ro n r _ ^ r> n cji ~ c ^ co> c ^ r o r T> oo o o ""-^ i n n n oo o r oo ai o¾ h <o> h

 o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

o o o o z o o o o z o o o o o o z o o o o o o z o o o o o z o o o z o

膽

ATOM >>>>>> ooooooooooooooooooooo ooooooooooooooo co ccccccc rND rsj rNo r rsj hh rsj ho r ^ ^ ^ ^ ^ ^ ^ ^-^ — »-oooooo

一 I 一 I 一 I

One I One I One I

CO o oo ^ oo CO oo o <ro CO o "■ J CO σ CO CO O CTI o

 o cn CO CO oo CO σ¾ o cr> oo CO CO oo CO o ro O oo cn CO CO CO O TI TI — 1 oo o CO C σ> cn o oo σ> cn cn ^ 1 cn -j cn CO CO> oo ^ -J ^. CO cn o --j O CO oo CO o

 1 1

 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 (1 1 1 1

 σ> oo σ¾ cn o O or ^ σ> <J> cn cn oo CO h CO -P ^ r> σ> oo OO oo O o σ¾ oo CO <y> CJl Jl C> σ> CO n CO CO oo CO O h oo o ho ho cn oo oo CO O CJl cn cn ro σ> CO ro oo ο CO σ> <oo 4 ^ σ O ho oo oo σ> o rsa Jl <y> CO oo cn σ Ol CO CO ho oo cn o ro

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

CO CO ooor> ro O ^ 1 oo <o CO CO oo o CO CO ""--1 oo o oo oo «» «-1 oo n σ¾ O CJl <> oo CO CO cn CTI CO ro ro CO oo OO ooo ro o oo -jh oo <σ¾

 OO cn cn h CD o¾ cn O CO σ -JO CO σ¾ -J o CO CO-^. Oo oo ro CO CO o CO CO ΟΊ oo CO ho σ> σ¾ O σ> O o σ> hho ro o cn CO σ > o ho CO CO CO CO o oo ooo O ooo O o O o O ο oooooooooooooo ο ooo O oooooo O ooo O ooooooooooooooooooooo ooooo

CO O CO ro C CO CO O CO CO CO O

oo cn CJl o oo oh CO r * o CO CO oo

r CO oo O <y> o¾ oo o oo o O o o O CO O oo σ¾ CO 05 CO CTI

CO oo OO -j CO o o oo o O Jl CO h CO o CO ro OO oo o 1

oooooooooooooozoooooo oooooooo

ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooo ^ ^ CC ^ CCCCCCCCC ^ C ^ ^ ^ ^ ^ CTl On CJl 4 ^ ^ ^ CCC Co rnco one no> o <one ro o ho oo one nt cn cc ai c « o rsD «^ c one oo c ^ OJ ^ co oi h one c one cn one co O" »« JO --- irr one or one "-1 <y> — *. — ^ OZOZO SE O Si OZ Si OZ

ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο σ ο ο ο ο ο ο sssssssssssssssss 1 1 1 ¹

 One one one

 o z o s: o z: z o o z o o z o σ c¾ CD 3 c> CD CD 3 · Ν Γπ ο ο σσ> σ σο> ■ Ω ΟΟ> one r one one t

 "" "" "1 1 1 1 1 11 1 <» Ο 00 CO CO G 00 rn m m rn rn "" "" "" "m m m m m m m

 ΓΠ ΓΠ ΓΠ ΓΠ ΓΠ ΓΠ ΓΠ ΓΠ ^ σ ^ σ ^ ο ^ ο τσ ^ ο))))))) Ο) Ο>

o> o> o> a¾ a o one o¾ oi j

 I Ο> · Ι ^ Γ \ 3 o

 CO o

— »IS3 CO σ

 One o o o

 One one 4. 290 one> o one one ^ o

 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1

 Ο ο One 50 00 0 ； —

ο ζ ο ζ ζ ζ σ ζ σ ο ζ ο

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

 : ≡ ≡ ≡ ≡ ≡ ≡ ≡ ≡ o an ^ c r 3 ^ o o oo-^ o¾ cri ^ o — ^ o oo ^ J os ^ C rsa — ^ o o

 z o o o o z o o o o z o o o o o o z o o o o o o o z o o o o o o z o o o

 00 j OD

 r one

 I

IIIIIIIIIIIIIIIIII tt IIIIIIIIII t II c — »-ho o — ^ or —»-oo oo co oo oooooon "-^ ι oo oo oo ι cn σ¾ --J o> r <0" »j co o¾ ~ ^ to cri ^ j oi ^ j oo h one o one ^ J cn oo 3 r o¾ no> oo cn one "* oo one

 c — * ■ σ¾ io> h oo o oo cri ai co ri o> co oi ^ -j co — ^ och ai cn o-^. cn r one oc σ ο οοοσ> ο σ one "" << J- -J coco ji c oo ro σ> i o ^ ^ -J oo ^ A oi ccr

 I I I I I I I I I! I I I I I I I I I I I I I I I I I I I I I I I I I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

CO ^ ^-^ J ^ ri o> oo ^ J oo oo oo — ^ -P ^ r ro c ^ ^ ^ j oo ι σ> αι an one r co j ^ A j ^ o¾ rs <o oo ^ j oo c co ooclo co on oi o oi os o cn ji oo o o¾ oo ai c oo o ai 4 ^ r to — * co — ^ orc co-^ joco ^ ι ro oo o ι "-ic o¾ ^ a¾ One o> oo oo o> o¾ c ai oco rsa --- ic one ro r to one o ji oi oi c co one * · θ3 · ^ 3 ο l oo co ho j ^ ο σ> οι one--J OO OC oo oo rc one hc ~ *> oc oo one o

CO — ^ Jl Cn O> ^ O> OO 00 ^ ^ h 00 ^ O CJ 00 J ^-^ oon co ¾D cn oo r> ^ o — ^ cn cj <^ co I cn σ> cn cc 4 ^. Ooooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooor rsD rrrr rsa one r ho rrr one rrr rsj i ^ hror ho one one one ">> · Γ Γ Γ 3

»« »J oi h 0 ^ ^ J O co co rvj O5 c o oo r« »j o> oo one oo c h h o¾ o one σ>

Ζ Ο Ζ Ζ Ο Ο Ο Ζ Ζ Ο Ο Ο Ο Ο Ο Ζ Ο Ο

o o o o o o o o o o o o o

一 一

One

 o o z o o o o z o o o z o z o o o o o o o o z o o o o

 ο ο ο ο ~ σ ~ σ "σ" Ό ~ ϋ ~ σ>>>>> j>>> m m m m m m m m ~ <~ ~ <~ <c: c: c c c cz cz: c = c o o o o o o

1 1 1 \ D c r> 1 1 o 1

one

 ^-One one one i one

 ^ o ¾. —

 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

o o o o o o o o one r>>-* one r ho o r c

 One

一 一 一

One one one

— — Ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooo -P ο one co o¾ oo one αι ο ο ο ζ ο ο ο ο ζ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο

0 16 "63 00 ■ ι 9 '6- z- 009 Π- V SIH 90 8 ΐει WOIV

0 80 3δ 00 Λ m '6- O z- O 06 93- 381 V SIH 90 O ιει WO 丄 V

0 38 ZZ 00 ι O 61 ΌΙ- m Λ- S68 "92- 381 V SIH νο 9ΐει WOIV

N 60 εε 00 ι 88 to 6- • o- 066 9Ζ- 281 V SIH Ν 9ΐει

0 8ε εε 00 ι ιοζ · οι- m .0 9CS S3- m V V1V 0 i WOIV

0 fri · εε 00 ■ ι ι · 6- o • 0 982 9Ζ- V v, v 0 mi WOIV

0 09 zz 00 ι 100 L- S 8 • 0 193 '92-m V V1V ζιζ ι WOIV

0 90 3C 00 ι 200 8− Λ 083 '92 — 181 V V1V νο \ m WOIV

N 6 00 ι ε6ε L- Λ 909 LZ- m V v, v Ν om WOIV

0 £ 6 38 00 ι 090 "6- 339 Z" 82- 081 V S people Ί 0 6οει WOIV

0 οε 'εε 00 ι 8 ^ 6 O-9 O 6 l 9 "83-081 V S people Ί 0 8οει WOIV

N 08 '6S 00 • ι 08 O 808 L 060 "63-081 V S person Ί ΖΝ WOIV

0 B 8 '8ε 00 • ι B 69 S- 918 9 9ZL 6Ζ- 08 L V S people Ί 30 9οει WOIV

0 93 '9S 00 Ί L9Z 9- 99C S 819 "62-081 V S person Ί 00 SOS ι WOIV

0 83 Π 00 Ί ZLZ 9- 816 62- 081 V SAl DO WOIV

0 η · ιε 00 ι 乙 96 9- 096 I 308 "63- 081 V S people Ί ao εοει WOIV

0 36 ΖΖ 00 ι L- 166 696 "63-081 V S person, νο ζοζι WOIV

N 93 ΖΖ 00 ι 999 9-9S9 Ό οε- 081 V SAl Ν ιοει WOIV

0 00 ∎ι ε 9 8-9 9S0 o- 6ΐο ιε-6 V fl, 9 0 οοει 隱

0 LZ 'εε 00 ∎ι L- 093 o- οΐ8' οε- 6 V fl, 9 0 663 L 隱

0 62 00 ι 3S9 '9- ε-εε ^ ss- 6 V fl, 9 330 8631 隱

0 9ε 00 ι 0 ^ 9 V- S9 • τ-m ε- 6 V fl, 9 130 WOIV

0 00 'ι m "9- 830 • ε-η-6a V mo αο 9631 WOIV

0 68 '00 ι L iZ 9- 030 • ε-931' εε- V fl, 9 90 9621 WOIV

0 O 9 Έε 00 • ι 6lfr, 9- LZ9-^ 69 ζε-6 O l l V mD 90 mi WOIV

0 00 ■ ι m '9-809-οη ιε- 6a V mo νο WOIV

N 00 ι 99 O S- 0fr6 Λ- ε93 οε- 6 O l V ma Ν 3621 WOIV

0 89 'οε 00 ι 8Z0 L- S08 \-90fr 82-8 V Π Ί 0 1631 IN01V

0 39 ιε 00 ι "9- 666 Λ- 886 2Ζ- V Π, 0 063 L 隱

0 66 82 00 ■ ι "9- 602 • 9-frSfr 83-8 8 l V Π31 ζαο 683 L WOIV

0 ZL 2Ζ 00 ι 9C8 "9- 9-m '92-V Π3Ί 8821 WOIV

0 10 83 00 ■ ι S "9- m-LLZ" 82-8 Otsul V Πyo, 90 腦 WOIV

0 18 62 00 ∎ι m 乙 18 ε- ILZ '82-V Π3Ί 90 9831 ■ V

0 6 ^ ιε 00 c tn O ZZZ ζ- εοι "83- sa V Π3Ί νο 5831 WOIV

N W IS 00 989 ε- 66fr ι- 96fr 82- 8 O l V nan Ν 腦 WOIV

0 9ε 00 • ι 63S Ό 96fr LZ- LL \ V νπν 0 983 L WOIV C00 / .00Zai / X3d 6 8 £ 0 / 800i OAV ooooooooooooooooooooo ooooooooooooo

m rn σ σο S C¾ CD CD> ο σ ο σο> ο οσ> ϋ m rn σ o r one h — * ro one r — ^ — * ho

 <<C <C <CC <<> '->->'->-> '>' "D" D "0 -D -0 -U -O IC ^ ^ IE IE ^" "" "" "" r ~>>>>>>> OOCCCC 0 C; ¾3; ^? D ^ D iO ^ D; O — one by one one c cz cz ci cc cz cz r "" "" "" "" " "σ" σ "σ" σ "Ό ~ σ ο ο ο ο ο ο ο ο ο ο οο οο οο οο οο οο οο οο οο οο οο οο οο οο οο ο ο οο οο οοοοο οο ∞ οο οο ∞ οο οο οο οο oο o> o a¾ o¾ o¾ o> o> n ji cri ri ri ji n 00 00 00 0 0 0 00 ^ ^ (\ 0 ^ 3

II! IIIIIIIIIIIIIIIIIIIII IIIIIIIIIIII ohr — »· — ^ o co o co oi o ^-« ι oo oo o co σ>""-— ^ oo — ^ o oo oo oo r ^ rsD Co co i oo-»jo o> o > oo co o¾ one «* j oo o ^ jh one αΐ Α Α σι αι ο one" ^ οο one oi rnn ^ · "-1 one <<-j one o one o> cri ^ one nh" o ^— o one rro A o o o o o co oo o οο 4¾ · OC 'Ti cri-"-io co c ^— a — one * n -——- j one nr -oh

ο 一

ο one

ro or one oo one oo one r oo "" * "<*» j rs3 0 one oo o¾ oco oo o ro nr co <oo ^ c7 cji co cnc ι οο one one oo noor cn ー ^ one on — ^ οο <σ> r oo oo oo oo hc co — »· οο — ^ ho noij ^ oi o one c to o to-» j one c co j ^ oo o ^ ^ J nh one oo ho oo ^ J ^ JO o¾ o ^ i co ch o¾ one "^ ^ 1 —» ■ O ^ ocn oo cj ^ ^ ^ cno oo ^ -j on «ι —»-* -j ro oo cr> oo co ro 1 — ^ oo to co ro — »-4i. Cnnj ^. Ji oo ^ J h cn oo one on o 1 cc oi one one ^ ^ ι cn ^ o ^ h>--« ι σ¾ — ^-^. — ^ Oo

- 二6 I o o o o o z o o o o o o z o o o o z o o o o z o o z o z o 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 occcchccccccccccccccccc cccccccc oo ooo One co one; One ^! ^^! ! ^! ^ ； — ^ ； 一 ^ ^ ー ^! ^ ー ー! ^ oo 1 no oo

-Two 6 I ooooozoooooozoooozooo ozoozozo

cccccccccccccccccc co ccccc co cccoo oo i o> n -c ^ co r — ⁴ -o <oo --J o¾ Ti-^ cr — ^ o oo --- ι σ> οι h one oc oo --- 1 σ¾ en zoozoo ^ oozoozo

 One one one

 <<<<

c "pk r 3 C r c 1 1 1 \ 3 1 1 1 1 1 1 1 1

 One

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1; ~ *>

 1 ^ ο ο

1 1 1 1 O CO O D OO O

^ o ο o σ¾ on 05 o ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο

h 0¾ O * -J <n C Cn «^ 1 JI t OOAO ri Oi O Ol 0> 1 — * <CD 1 ΟΊ 3 Γ ^""--1 or 1 ^ ^ rs3 j ¾ -Fs-*-J o rs3 — * ■

0 oo 'οε 00' W8 'm ζ- m 2Z- 961 V n Ί 90 9zn V

0 06 "62 00 'I 6a' 6 m ez- 961 V n Ί ao W01V

0 SO 00 'I 6 B 0 01 9ΖΖ Ζ- oi οε- 961 V n Ί vo nn 隱

N εε 'εε 00 I m' 6 ζ- 'ιε-961 V Π31 N u I / JOIV

0 00 Λ 061 01 O 9 O ιε- 961 V AID 0 zzn W01V

0 z.8 'εε 00 Λ 96 6 339 ε- 901 zz- S61 V 9 9 izn

0 LO ZZ 00 l "9 '8 Ζ89 ε-38ε εε-961 V kid vo o V

N zo zz 00 Λ 100, 6 90 .fr- η- 961 V people, 9 N 6in WOIV

0 99 38 00 t B 6L, 8 9S9 ε-990 9ε- V N, 9 0 W01V

0 n zz 00 l 9 8 m m 9ε- ηι V N19 0 WOIV

N 6 Ofr 00 Λ B 96 21 UZ '8- ISO' 8ε- V N19 33N 9lfrl IN01V

0 19 00 Λ 913 ει S60 '9- LZ- πι V NID 130 WOIV

0 91 00 Λ 98 0 L-is LZ- V NID ao WOIV

0 3i O ε 00 Λ 9 O 6 01 m '9- 189 LZ- V NID DO i WOIV

0 16 εε 00 Λ 9S9 01 s- ss B 9ε- V N19 90 IfllOlV

0 so ιε 00 Λ 190 '6 998 S- 9ε- V N19 vo i WOIV

N 0 63 00 l 931 L-91 O 9ε- V N19 No om IN01V

0 CS "83 00 l 099 9 810-9 l9ε- V dSV 0 mi I / IIOIV

0 0 LI 00I 929 399 L- 6ZL 861 V dSV 0 I / IIOIV

0 68 "93 00 l 2ΖΖ '6 m u-10 B-86 L V dSV ZQO Thigh WOIV

0 98 83 00 l 916 O 99ε w- V dSV mo 9o WOIV

0 63 "93 00 l 8 LZ9 'εε- V dSV DO WOIV

0 s O n 00 Λ ZL1 2 Z9Z 6- 068 'εε- £ 61 V dSV ao Simplified INOIV

0 00 Λ LH L 6-991 9ε- Z61 V dSV vo WOIV

N LZ 9Z 00 Λ m S εοε 6-968 m V dSV N WOIV

0 00 Λ s ηο · οι- · 9ε- Z6l V 311 0 Yang WOIV

0 88 '93 00 • I 991 S L · 6- LZ9 "98- 361 V 3, l 0 00 隱

0 8G "93 00 I 19C Ό '8- 9ε- 361 V 3, l ιαο 66C 1 WOIV

0 08 "82 00 • I LZZ i 999, 6- m9ε-361 V 3, l LDO 86ε ι WOIV

0 60 93 00 l 130 ε m L- 99ε 9ε- 261 V 311 390 Expansion WOIV

0 88 3 00 l L2L Z L £, 6- 6 9ε- 361 V 311 90 96CL IlilOlV

0 91 9Z 00 l ILO 01- 9ε- 361 V 311 VO S6SI WOIV

N IZ LZ 00I m ε frlQ U- 919 ss- 361 V 311 N mi

0 20 6Z 00 I 918 ·-863 εε- 161 V y s 0 mi WOIV

0 n LZ 00I 9Z9εZLZ Zl- 9 κ- 161 V ms 0 meta WOIV

0 00 l 9C0 9 068 ει- L9Z 161 V 90 i WOIV C00 / Z, 00iai / X3d 61-T8C0 / 8001 OAV 3>. 3>>. 3>

c ho h ho ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο ο ο σ ο ο σ ο ο ο

c ho h ho

 59 — * ο o ζ ο ζ ο ζ ζ ο ο ο ο ο ο ο ^ ο ο ζ ο

 3 58 m m σ 3> 3

 One r r — »■ ro —» ■ ho — * ·

~ I C5 C¾ C¾ C¾ Z

 ■ <"" "" 457C

 1-1-1-1-1-1-1-1-1-1-I-i--1-1-1-1 "" "" " "" Co oc GG ooommmmr ho rrr 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 <~> oooo <45 <<co cc < co ooc co tccoottc <co otc <co c — ^ ooooc 5c co co co (occ oo oo oo oo oo oo oo oo oo σ¾ σ¾

co cc '-j oo -p ^ ro o oo oo o ^ oiorir oo — ^ ^ c oo croo —>-oo ^ c ι no oo co ^ · i oo «-jo — •• oi co oc — ^ o oi h oo to oo ^ ^ o cAi co co ccoh — ^ O

 0

 oo co oo ic ^ JO) ro) 0) 0 o one ro AA o ^ nrr co ji oo one roocc oo oo o oo oo) oo co oi or ^ oo oo cA3 0o oo) 0) 0) 0) 0- J ^ r co c oo <o 4 ^ one n one or ho co one 49 co one o one <o one oo cn o ts3 C «" »J ¾ o> oo * -j one 0 00

 48

 to oo oo oo one σ¾ ο οΐ ο ο ~~ »· οο oi o

 h o¾ oo oc one ο σ¾ one ι nno 47o rchc one co cn o¾ oo> oo r co o o¾ «^ o — *" O oo n ^ I ^ CCOO ^ J 1 o oo noooooooooooooooooooooooooooooooooooooooooooooooooooc nnncrhr ro cccooi> ^ x> occ oo oo oo ^ ^ ^ wooj> r O "« J Oo cri i o¾ oo ro — ^ oo oo oo — »-cn c oo o> -j-^ co-* j 1 — *--* J-^ J Oo oo> ho oo> ^ <oo oo cn rs3 c 1-^. O 1 i oh o¾ -jo> i oo ji "-I OO ^ J ^ ι οο σ> i co oo oo co cj> <occr oo o (0 ^ one ro r

zooozoozozoooozoooooo oozoozoooozoooo

ooooooooooooooooooooo ooooooooooooooo

 ζ ο ο ο ο ζ ο ο ο ο ο ^ ο ο ζ ο ο ο ο ο ο ο> c¾ σσ 3 ϋ ο οσ 3> ο m N m o m o c5 0D>

― ^ — ^ Ro — ^ ― ^ h h r

o o o o o o o o o o o o o o o o n A c c c c co c c h rsj rNo r* h r 一 一 一 一 一 一 一 一 一 一 一 I I I 1 1 I t I 1 I -<-<ooooooo TO TO ooooooooooooooooo

oooooooooooooooon A cccc co cch rsj rNo r * hr 1 1 1 1 1 1 1 1 1 1 III 1 1 I t I 1 I

 o 1 o 1 1 c ND 1 co co ^ j oo o to <o -j oo «-j 1 ro h 4 ^ c« p ^ 4 ^ o> o> rc oo co co σ> "-1 cn- -io> ch ~ »> o¾ c o¾ co co co o> ~ p >> 4 ^ h oo one no ^ c oo cn r one o I

 One o o o One o o Ol

 r <o¾ cn c ho oor * o «^ oi --jr" ro co c oo on o¾ "^ o oo ai ro oo ri r> oo co ^ ^> ho oi" -J OO-«J οο σ> ^ i ^ oo cnco ^ ho oo nci co oo 一 ji ro c oo ■ «cji O n i) o o no ro coro co oo i; i ^ I Ι ^ θ i) OO C OO CO C0 4 ^-^ 0) <OO ri 7l ^> O> OO CC OO OO C <0 ci ^ o ji on ^ oo o> ^ o> <to — »-co cri h ri ^ * -j <ooico <o co ¾ o¾ r one c oi c one cD o co o — ^ nc oo — ^ oo h co ho> o¾ o¾ rs3 ^ jooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooor one co one ^ j oi one co one o-"* ho ^" J ^ c i oi OO ^ J t oo r co i r 1 n oo o¾ on

O Z O Z O O Z O Z O O O O

n h — * oBox ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο sssssssssssssssnn en oooooooo

nh — * o

O O O O Z O O O Z O O O O Z O O O O O O O Z 0 0 0 2 0 0 C5 0 0 0 0 Z O O σ o> σσ> σ σ> σ c¾ σσ>-One ro — »■ h

 >>>: ">>>> C5 C¾ CD>" "" "" "C5 C¾" "" o o o c c c o "" "m m m m m m m m"

 ">> -υ -σ -υ -υ -ϋ -σ -σ -υ-<-<--<cc: cz: cc cz c: c:-<-<ooooooooooooooooooooo oooooo ····· 1 hhrh ro rrhrhh ho ro ro rrrhrr ho

-^ ^ ⁰ ! ^ ! ^ ； — ¹ "； — ¹ " ； ^; ^; ^! ^! ^! ^ ： — ¹ "!. ^{3. 0} P ^ i ^" ¹ ! ^? ⁰ ; ^ ¹ ? "^ ⁰⁵ "- ^ ^{1 00 0} * ⁰

I OO «« JO> 3 _P ^ One 00 h ** JOC 7l 01 0 Or O One 01 01 00 0 01 ^ 3 00 One oo oo One c — ^ σ io> c oo o> o¾ co oooo One o¾ c cn o>-»j oo ^ j o¾ ichi ^ ι σ¾ ο σ¾ cn οο oo cca ^ co co o ^ jc oo oi oo one no> oo <c o¾ oo one σ> ι« ^ ι σ> r — *-Cn o

 I I I I 丄 I I 丄 I 丄 I 丄 I I 丄 I 丄 丄 I I 丄 I 丄 I 丄 I 丄 丄 I 丄 i 丄 I 丄 I 丄 I

• ^ c jSfc oi ichi js »" one co one n ^ rc * 3 0> o> O "^ ~ * c ^ J ^ JO rco cji <o ^ jn ro one o oo oi co ji one ro o¾ one 3 0 ~ * ^ 1 co o> oo c 1 n oo 1 ^ cr> h 1 oo co ho 1 σ¾ 1 00 ^ 0 "" "Ji c 1 oo ^ CT> *" joo 1 ο οΐ ϋπ ccj ^ ； 0 <Ρ τ ^ ί? ° One r oo oo o¾-^ co ro —-ji oo to o co o ^ -jr — »-co <oo ι <—» · <ο — »-CA3 oo r-^ o> «-jo cri c ^ ι h -t ^-h oo oo cn σ¾ ico oi oo h o¾ co — ^ co oo to oj ^ n — ^ o¾ n ro r oi cn ro --J o 3 o O o o o o o o oo ho> cD or cn o¾ o¾ n ai ^ -j to hc oo o oo co oo ooooooooooooooooooooo ooooooooooooooooooooooooooooooooooooooooooooo ooooooooo oo ai ccc one r co ^ i ^ ^ o ^ oi ^ ^ in ^ ri-i ji -p ^ co n cn oo-«-4 --jf« "^ co cn oo o> oo ^ j one oo oo h oi o> cji ^ one o oo c oo ^ ic to oo h co oco oo n one o> co oo co o5 0 co one co one oo co c one os one oo co o one to co

oozozozoooozozozo

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o n n ai d ji n n n oi n oi cn n ji ji ji ai ji ai ji ai ji ri n ai ji ai n ai n n on n n

Z O O O Z O O O O O O O O O O Z O C5 C3 C3 0 0 0 Z O O Z 0 0 0 0 0 2 0 0 0

 > Π ΓΠ Γπ σ σ σ¾ σσ> σ σσ

 1>-rim σ c¾ TO 3 σ h 1 1 1 1 1 1 1 1 ““ ““ ““ ““ 5 3 3 é ”“ ェ 工 ェ ェ 「” "" "" "" ■ ■ <"

"<~ <Rn mmmmmmmmmmmmmmmmmmooo o oo ooo co" D "o ^_ o σ¾ αΐ υιυπ απ 4 ^ ^ · ^ << ^ cccccccchrrrh ho rrr one one one one one one one one one one one one 1 r 1 1 1 1 1 1 1 rrhh 1 1 1 1 o ^ jj ^ o¾ oo oo to oon -jccc o> or ο οο σ οο — * oc ^ -j cn cn-^ ι -t ^ «ι oo ni o¾ hor — »-o> on 1 co o one c co oi OA oo one i co o <hoo ^. ^ — ^ h

One οο ο οο · * »ϋ ο οο αΐ ο οο οι ο οο ο οο θ Γ ο ο ο οι ^ αι-» · ϋ οο One σ¾ One hco One oo a¾ ^ jo One cch 4 ^ o> oo c oo 4 ^ oo cn ~ ^ h oo one co co c one i cn-«-JC n cri oo o> _ ^ ^ (ο οο το υΊ θΊ θ <ο σ <ο ο ο ^ οο ο <^ ο ο ο οο οο ^ σ> 4 ^ οο οο ο ο ο "" >> J

 oo r

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o oo 一 r 一 r 一 r h r ro o r r r h h h h 一 一 一 o r r c c ho r ho r h h c oo n **j c h o¾ o — ^k C a¾ "-- 1 o o> oo h co c

一 oo One oc co oo one

ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooo oo one r one r one rhr ro orrrhhhh one one orrcc ho r ho rhhc oo n ** jch o¾ o — ^k C a¾ "-1 o o> oo h co c

One oo

zozoooozoooozozoozoo

CO

o co c C C A JI c r o 一 o 一 00 00 ー O «-J «^J 一 o c c oo --- 1 σ> ΟΊ ΟΊ co ro co ^> cn co co co 1 co --- 1 1 cn 05 cn co o --- 1 -J -^. "-- i o¾ -ts. — ^ n oo -j oo oo — ^ co o oo σ> ^*. oo ^ -«J n o c n 一 c to 一 ro O¾ 00 rs3 ^ CO O> O C — ^ rsD C7 Jl --J — -- oo σ I ro 一 o ^ ji c h ai -*J 4^. o> to o ro j^ o -^ o o¾ o c cn o ji ji cj c o co o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o c c c c c c c c c ^ ^k. ^ ^ c ^ >^ <r^ an ai j^ c h h ho r r roo

o co c CCA JI cro o o 00 00 ー O «-J« ^ J i occ oo --- 1 σ> ΟΊ ΟΊ co ro co ^> cn co co co 1 co --- 1 1 cn 05 cn co o --- 1 -J-^. "-i o¾ -ts. — ^ n oo -j oo oo — ^ co o oo σ> ^ *. oo ^-« J nocn one c to one ro O¾ 00 rs3 ^ CO O> OC — ^ rsD C7 Jl --J —-oo σ I ro i o ^ ji ch ai-* J 4 ^. O> to o ro j ^ o-^ o o¾ oc cn o ji ji cj co co ooooooooooooooooooooooooooooooooooooooooooo ooooooooooooooooooooo ooooooccccccccccc ^ ^ k. ^ ^ c ^> ^ <r ^ an ai j ^ chh ho rr ro

^ co co ^ ic one o «^ oo o> one oo o¾ co ^ J os oo ri cD o ji ji rr — *-co oi ^ ι-^ ^ JO><o oo oi O" -J cri c <o co — * r-^ oo co one coc one σ · ^ one oo one oi <oo o> ζ ο ο ο ζ ζ ο ^ ο ο ζ ο ο ο ζ ο ο ο ο ο ο

>>>>>>>>>>>>>>>>>>>>>>>>>>>>

 Three

 One

 -<-------<-<"" "" "" "" "^!

 One

One one

 1-> 1 1 1

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

«^ O¾ ^ J n cji o¾ 1 1 1 1 — 1 1 1 1 1 '1 1 1-

匪 0025.

CT> σ> σ¾ ο¾ σ¾ σ¾ σ¾ ¾ ¾ ¾ σ¾ ¾ ¾ ο¾> ο> ο ο) ο> ο>>) σ¾ ο) ο> ο¾ ο σ> ι> ο — »· ο οο io> oi ^ ch O oo io> ji 4¾ »c —»-oo oo * -J o¾ ri-^ c ζ ο ο ζ ο ο ζ ο ο ζ ο ο ο ^ ο ζ ο ^

 N m o c cr> cr> σ σ ro 3> σσ 3 σ m m t one r one

 "" "" "" "M rn rn rn rn rn rn rn? D iD iD ^? O io ^ o

 1 o 1 o o o o o o o

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I t I I r r ho c c c c c c c c c c c c r r r r r h r ro c c c c c c c c co o oi co co one o one r rsD one o oo c p>-

0-^ oo ^ co nr ^ jc cji o> — ¹ ^ ι o ι oo »-j oi ^ i <i o" oh oo c o¾ j ^ oo i rc <cn co co-^ p ^ rncc ^ jinrn o¾ ooo r> cn --j one h --j-«J h co o¾ oo ji c ~""C ~ ^ o> cn one ooc oo co o oo ^ o oo ¾» --j--j

IIII f IIIIIIIIIIIIIIIIIIIII IIIIIIII 1 I cccor ro ho cccccrcr ro rhrr ho ho rrrhhrrao ro or one--j oo oo co o one or one oo one o co o ¾ "ΐ ¾;-ΐ ρ¾ σ> | ^ σ> n oo cr> ^ on cn oo i <o — '■ ^ -J Ji -T ^ n-^. o oo j ^ o — ^L r "-1 o ro i oo o¾ oo oo oo oo oo on oo ^ joh cji onrc —-co o¾ — ^ ο σ¾ --- — i co <3¾ c rN 4 ^ r cj>T> ri — ^ oo r -— i co n — ^ rso c — »· en n co io 3 CJ oc <o oo hcho — ^ cn c --jc one oo oo one one r ro

 ^ I to oo — »■ o o ^ ^ n -J

orn C 4 ^ CTi s3 rs3 00 O 00 C O¾ i0 4 ^ ^ O> Jl Jl C 00 O CJl 3-^ J '-* J r rO ^ O 00 00 O5 ro oo oo n oo <o one ""- «I fsD Oo r> c — ^ ro ^ — in« ir o¾ oo j> j¾ ^ — i ^ — ^ -p ^ oo c ro

^ <0 i o> ji ro co oo c one oi oc one ι οο one rc

z o z o z o sr o z o o z o z o

27.00

 --j --j ^ o> o) σ¾ σ¾ σ¾ σ¾> σ> σ ο> σ¾ σ¾ x>> ο>> σ¾ ο> ο ζ ο ζ ο ο ζ ο ζ ζ ο ο ζ ζ

σ σσ 3>> σ σ C σσ>-ι ι m ο σσ ∎ m m ϋ σ σσ>-r one r one h one one

 "" "" "" "C3 G> o o" "" "" "m m m rn m m m m ι ~~ ι" ~ "ι" ~ m m rn m m m m m

c en o¾ -»j 一 σ> --^ οο ο σ> σ¾ ο:> ο οο ςο Γ ο ^— j c o r r n cn c oo ri σ cn σ> — »■ 一 cn cji 4^ (o ->j o co oo <o _^ n o) "-j 一 fa ro ro ro h ro ro 3 ro hhrc cj

c en o¾-»j One σ>-^ οο ο σ> σ¾ ο:> ο οο ςο Γ ο ^ — jcorrn cn c oo ri σ cn σ> —» ■ One cn cji 4 ^ (o-> jo co oo <o _ ^ no) "-j one

o-«j 1 t 1 1 ol 1 r ho o to 1 n-» j oo cj c co o r h

I I I I f I I I I I I I I I I I I I I I t I I I I I I I I I I I I I I I c c c c c c c c c c c c c o c c c c c c c c o c r ro r ro c ^. C ^ cri o cn o o> ri r »--j o» oo-^ i c7 cjn o

 no σ¾ en roo -i ^ oo ^ ^ h oo ooco-*-JO c cji no> <-*. -P ^. en --- ro σ — ^ ^ co oon c7 nno> — ^ o oo ^. en oo n 1 1 1 1 1 1 rhr 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1-^ 1 1 1 1 1

■ j ^ o ho o i "^ i co ^ j co ^ jo ji ichiichi h oi O" ^ o ji hO 3 0i i cji ^ A n i ^ oc i ohc oi oo> n cn c ho oo ^ ~ ^ o> "^ io oo c oo c ri one <o oi o> ^ oi co one ^ o j¾ cr co one cji ho one σ> ίο σ¾ σ¾ one cj — ^ --j ho a¾ oo hro rs o cj ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooco-k. h oo i o¾ r 4 ^ n o¾ o> ^ j 0 ^ co — ^ οο οσ¾ σ>-^ — ^ aro co ri CTi O r 3 0> c «^ o 4 ^ oo oo one h oo one σ¾ one isj oo ho oo one o co co o ^ "-1 r 1 o σ¾ ro on zosoozozozozzoo

膽 ΟΊ · ^ _Ρ ^ ^ · ^ cccccccchhhrrhhrhh ~

o o o o o z o o o o o o o o z o o z z o z o o o o z o o o c o o o z o o> οσ> rn σ οα

 to occcccrrr ro rrrr rN r ro rrhrrr ^ hr ro rrrrrrrroooooot to oo co co c <<oo oo oo oo oo oo oo oo oo oo oo ^ ^ ^-«j-» j-«« j σ> cr> rrhr po ro or ro rsD r ro rorhrpco co o rNj r ^ f ^ ji oi crho <

c ^ — »■ --j ^ <ooo σ> ^ — lo — ^ Ai ji oo -j oi Oi-^ c — ^ o oo o oi — ^ ho cri co 1 o <σ¾-on oo o¾ ho *- J Oo 3 n "-" «i co n ^ oo ~ ^-^ j-^ c NJ CJi oo o oo ai cj cn oi oo-^ ooh-^ j

 CO CO CCCCCC cccc co c σ> oo oo oo o oo o oo oo oo cooo — ^ OO CO OO OC OO OO-^ J r cx5 J> ho cj ho o cri o oo — ^ iho cn co — »-ro r co ro <00 0¾ OO J1 C-* JO OO J1 ^ — ^ Ol ^ J ^ jc ^ cn oo c oi O — *-o oi o — ^ οο σ¾ — »-c ro — * oo c

--O c t * -j 00 Γ "θ σ> ο σ¾ οπ αι

 I I I I I I I I I I I I I 1 I I I I I I I I I I I I I I I I I I I i 1 I r p h r h r h i \ o h r r> h r rN r h r r r h h po h r

CD oi j ^ j ^ c c O o r o r Γ *; ~ ^ [a jva ^ o lO pJ j ^ j ^ i A Oi Oi ^ -j po c oo

— ^ O cT5 4 ^. — ^ Oo onn ^ — ^ r> rnoo-^ or-«j ^ i ro c —»-oo o> rn oo oo chocoi ho oc ri ro-^ -p ^ 7i ji) c ^ c oo- ^L oo oo --- J ^ 7> oo --- 1 — * — »■ o cn cno ~ ^ cror -p ^ n —> ^ — ^ n oo ji — ^ T>r> — ^ o cr <o — ^ rc ^ nor — ^ ι ooooooooooooooooooooo ooooooooooooooooooooooooooooo ooooooonn cn nnnncc co rcc cJ CJ J oro ho rh ^ ^ ^ oo c? iccc ^ co ^ ri c a¾ w ^ oco ^ ^ oo oo oo ^ ch cn co cn o¾ rsD C o¾ co> o oo coo ^><o^> 0 1 \ 3 «^ <<cn hor oo oo

OO OO ^ J tO OO O O "-J O C-* J C 3 0¾ -P ^ 1 Cn O> l Ol O C C Oi CO C« -J C 0O "-J

籠

 謹

隨 麵 ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ^ oozoozozoooozoz DO Ci O—> Ό3 ^ CD 7 οσ ^ ^ 00 ^> ΓΠ one one j> or one h

I— I— I— I— — I — I — I — I — 1 — I — I C C O O O G 1 1 1 1 1 1 3 ·> · ·> 3 5 ·

_ _ _ _ _ _ _ _ | 11 111 111 111 111 1 "?" 1 """""""0 0 0 00 0 6 0""" cn ai cn ai J ^ J ^ C cccccoo rsa r ro ro ro h one one one one one one one one oooo ro

 ■ ** j <^ n o¾ o¾ — ^-^ n oi oo oo ""--1 an-»iro> ro oo oo --j oo o¾ oo one ooo one ^ o cn cj> — ^ o cn ho to cn co ^ — ^ c <oo> ooc ^ — ^ --- cooc-r --- — * · — »■ ro σ> <

00 A ^

 4 ^ c one co

oi cn co co o> c one oi co no-^ o — ^t ^ jo> hooo o¾ c oo <— ^ ο σ¾ — '■ ai hoo oi o¾ h oi one oo oo ro ^ j one an oo oi c oo -^ j oi o ai oo to ^ oo ^ i on ^ ""-c co o i o cj c i ^ J Oi os ai nc oo <o cn i cn oo c o¾ o> ~ »" h o¾ i a¾ co oo ro ai ji one

IIIIIIIIIIIIIIIIIIIII IIIIIIII 1 II 1 I 1 I 1 1 1 1 1 1 1 1 1 1 — — · 1 1 1 1 — · * 1 1 1 1 1 1 roprrh ro rso ND orcoo 1 1 o co oo ji n oi --- i-** J o>-*-j ^ J oo oo ooccc ho — * r> — ^ rsa os

4 ^ 1 ^ — ^ oo ro ooo ^ — »--« J ri ^ ri ^ o-^ ^ -j ai-^. C 4 ^ *-J co a¾ o ^ ι n — ro oo n ^. Co One oo c one one to o one ooo oo one oooo cn co> one oo oc on oo o one co one oi ^ oi hoooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooooooooooooooo

CCCCCCCCCCC> ^ CC ΟΊ ΟΊ ΟΊ ΟΊ · ^ ^ o oo o rsD One o rr o¾ co o oo o5 ^ j "^ o One n cn to co One o cn rno ^ 1 One" -jnrco — ^ o oi to oni ^ to o co ^-^ rr — *-oo co — ^ r co ^ ^ ai ro o -t ^ cri -t ^ oo zooozoozozooooozoz

N IS οο ■ Λ 869 L- 69 '9 • 6 to 88 g ZHN 3381 ■ V

N 33 L9 00 'I 990 O-119 "^-991 ■ 61- g LHN 1381 ■ V

0 06 19 00 'I m L- 6' 6 G βε 9 ZO 038 L W01V

N 9609 οο ■ I m 9- 6817 S-893 ιζ-8C 9 3N 6181 WOIV

0 90 P 00 I '9- ιζζ n- εΐβ ΛΖ- 8S 9 9dV ao 8181 隱

0 00 I ε ε L- 19-zz- 89 a Dyv 90 18L 隱

0 IP 9 £ 00 I Z9L, 8- 90fr-zz- 8δ goav 90 9L8L

0 89 ε 00 l 0L96- 699 '-zz- 88 g VO 9L81 隱

N οι ιε 00 l 89601- 6-11- 8ε 9 oyv NV

0 οε 00 1 9ε B-06C lfr- zu n- LZ 9 Hd 0 9181 W01V

0 39 'οε 00 Ί 936 U- 998 Ifr- 89-LZ 8o Hd 0 3181 IftlOiV

0 S3 'οε 00 Ί 996η- LZ- LZ gyo Hd ZO 81 WOIV

0 66 '乙 Ζ 00 t OlL Zl- 88ε 9Z- Li g Hd 330 0181 WOIV

0 92 'οε 00 l 936 "91- 139 ε ^-m" 93- B ε 9 Hd 130 6081 1 / ilOlV

0 ΖΖ 92 00 l 6ifr ει-ii 90 η-izv "93- LZ 9 3Hd 300 awakening WOIV

0 \ L Z 00 l m "9i- ΖΟΖ-εει-LZ g 3Hd ιαο 匪 W01V

0 00 l B 9ε 卜 'ε G 909 n- LZ g 3Hd 90 9081 WOIV

0 9962 00 L 131-u- LZ g 3Hd 90 9081 W01V

0 00 • I ει- ε8-910 Zl- LZ 8 3Hd VD

N 00 l 931 et- m ΪΖ- LZ s 3Hd N ■ WOIV

0 00 I LLZ Zl- o '6ε- 990 zz- 98 g oav 0

0 w εε 00 l 639 Zl- 693 ΛΖ- 98 9 0 隱 WOIV

N 186ε 00 I 006 21- IL £ "9S-099 • si-9S g 3HN 0081 W01V

N 8 00 i 9 -B 8s B ε-Ol B l- 98 g LHN 66Π W01V

0 S9.6S 00 I I 0921-B 8B "99-m '91 -98g 9MV ZO 86 1 IN01V

N ο '乙 00 I 6 ει- 019 9 9ε- 998 1- 9C 9 DdV 3N 6 1 1 WOIV

0 ε9 · 9ε 00 l 993 ει- o Li • 6 G 9δ 9 9dV ao 96 B 1 W01V

0 89 9ε 00I on, 8ε- m 61-9 9 9dV 90 96U WOIV

0 98 SS 00 l 608 · ει- 6096ε- ■ 61-9 9 9 9dV ao mi ■ V

0 66 Ρΐ 00 • I S8fr Zl- frlO'Of- • 61-9ε g 9dV vo W01V

N εο 9ε 00 I 890 ΖΙ- 812 1 ^-∎ 61-9 ε g 9dV N z 隱

0 08 i 00 l 6 001- ΌΖ-9C g S people, 0 16 I 隨

0 39 ε 00 l 99801- 6ε-L9Z 61-98 9 ki 0 06 O I WOIV

N 03 00 l 96901- 909 '6ε- m n-9ε g S people, ZN 68 I WOIV

0 8 to 00 • I Otsuto 9 · 6-C6fr 0 639 n- ε g S people, 30 88 隨

0 00 l 0886- 9εε ofr- 601 91-9 9ε g S people Ί ao Lm WOIV C00 / .00Z3I / X3d 6 8 £ 0 / 800Z ΟΛ 丄 ΌΜ

Μ Ό

οο οο ΌΜοο οο οο οο οο οο οο οο οο οο οο οο οο οο οο οο οο οο οο οο οο οο οο οο ο οο οο ο οοο

 ΌΜ Two Μ

Top ΌΜ. Up

 丄 Up σ ο σ ο ο ο ο ο σ ο ο ο ο ο ζ σ

Up

 Two

ΌΜ 18

0 00 '62 00 'I 899 9- 668 IZ-19 LZ- 8 g n, 0 Awake I / IIOIV

0 89 '62 00 I m 9- 103 'εε-9999ε-8fr g n Ί 0 8681 1 / UOlV

0 89 3 00 I 62i n- 9LZ 9S-8fr g Π3Ί ZQ Awakening 隱

0 63 ZZ 00 I L98 01- 919 9ε- 099 ss- 8fr a Π3Ί ιαο 1681 隱

0 n LI 00 I S86 "6- 6εο 9ε- S 8fr 9 Π31 DO 0681 IN01V

0 8Z. ■ 9Z 00 l m 8- 96Ζ. Η-386 '9ε-8fr a Π o ao 6881 隱

0 28 '83 00 I 680 '8-ge' εε— ^ 8 "9S- 817 g n o Ί o 匪 WOIV

N 03 LZ 00 l 886 L- 988 2ε- 68fr G- 8fr g nan N 匪 V

0 ε O LI 00 I m L- 69 Oοε- 280 '9G- g n o Ί 0 9881 WOIV

0 S B LZ 00 I m L- 819 IS- m G- LP g Π3Ί 0 988 L mioiv

0 ZZ ZZ 00 I 80 "8-931-OG- LV g Π3Ί ZQO 匪 IN01V

0 98 '00 L 083 01- 961' οε- ll \ • οε-g n Ί ιαο S881 WOIV

0 88 00 l 888 '8-ο οε- • οε- g ηo Ί DO ■ WOIV

0 91 '00 996' 8-6 'οε- \ L g η ョ 90 隱 WOiV

0 00 LZ 00 I 8S L- LIL-L g ηo, vo 088 L WOIV

N 69 LZ 00 ■ I L "9- οε ζζ-6S6 • ιε- LV g πo, N 6 B 81 WOIV

0 31 93 00 ■ I 386 fr- ζζ- 866 ζζ-9 g 0 ■ WOIV

0 31 93 00 ■ I 869, S- ι 乙 9 ζζ- S9l ζζ-9 g y s 0 "81 · WOIV

0 09 dZ 00 l LZZ 031 38- CZ8 "62-9 g s DO 9 O 81 WOiV

0 IS 9Z 00 l 066 3 ie xc- 898 6Ζ-9fr g d3S 90 S B 81 隱

0 S8 2Z 00 • I 891 S- cos c- 063 ιε-9fr 9 VO WOIV

N 9Z 00 • I 190 9-ε96 η-B οειε-9fr 9 ms N i 隱

0 93 00 • I 896 9- 689 εε- fr 9 people 9 0 zm WOIV

0 38 9Z 00 l 068 "9- 199 S8- ζζ- fr People Έ 0 im IIUOIV

0 IL ZZ 00 l 9S 'O-HL 9Z- 008 ■ ζε- Sfr 9 people "19 O o WOIV

N εο ZZ 00 l 60fr "8- '9ε- 6 ^ 8 ιε- g people, 9 N 698 L WOIV

0 36 ZZ 00 l 0 B 6, 8, 6 Π- L £ £ ί- g 1VA 0 898 L WOIV

0 00 ■ I 601 · 6- 993 "9δ-98fr • ιε-g 1VA 0 WOIV

0 83 00 l LZ Zl- οι se- 889 g 1VA 390 9981 WOIV

0 8 O ZZ 00 l C98 U- 689 SS- 900-g ΠΥΛ S981 WOIV

0 LL n 00 l 6½ U- 628 SS- 08S οε- g 1VA ao 霞 WOIV

0 OV n 00 I B 01 ΌΙ-6fr6 ε- 98 £ 'οε- g 1VA VO ε981 WOIV

N LI '00 I' 6- 391 SS- 980 6Ζ-8 1VA N ■ 謹

0 Ofr 83 00 I 93 L '8-8βε εε- oee 63- g PHD 0 198 L WOIV

0 83 93 00 I 8S9 "8-ιεε κ- 199" 83- g mo 0 0981 IN01V

0 92 00 I εB 6 "8-οΐ8 'εε- 9SS ιι- g niD 330 6981 WOIV C00 / .00Zai / X3d 6 8 £ 0 / 800Z OAV

 CO C to OO CO CO o to o to to co oo co co oc co oo oo oo oo oo rh ^ rso rrh ho — ^ ooo 0 0 0 0 0 <0 <<CO o oo ATM-Oj o¾ cn-^ c ho — *-o co 一

o o z o o o o z o o o o o o o o z o o o o o o o o o o z o o o o o o z σσ> AOMT com m m σ σσ 5

 3 3> ·>-0 0 0 — I — I — f — l -H -H

 "" "" "" "" "" "■" ■ <· <cri cn ji n cn n cn ai oi oi ji ai ri ri ri cn cn cri cn ri cri cri cn cn ai n ai _ ^ cc ca rNj hr rNa h — *-— ^ — *-— *--^-*-— ^ oooooooooooo <ooo to <occ ca cc co o one — * · oo σ> ""--1 co-^ oo in cn nn cn nn cri o¾ c7 1 σ> en en σ

 ATMO oo co r co oo

co oi oi oo oon-«-J 3 0

co oi oi oo o

I I I I I I I I I I I I I I I I I I I I I I I I I I I I f I I I I I I I

I I I I I I I I I I I One I I I I I I ί I I I I I I I I I I I I I I I I I One ^ 1 01 0) <0 <0 90 7> ー

oo co ^ ^ n 4 ^ rc --- 1 ^ nhn 1 co ho <o 4 ^ 0)-«ι ichi-to o ho occ oo o co D o ai c o¾ — ^-(^ ^ J ro — »·· ^ ι i —oo co oo h co cn --j <oo) oo o> --jcooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo oooooooooo

一 o o oo 一 oo o o o < co 一 一 o> o ο ζ ο ο ο ζ ο ο ο ο ο ο ο =ζ ο ο ο ο ο ο 2: ο ο ζ ccccccchcrhhhhoo oo oo oo ro o> oo r — »-on o>o> cji

One oo oo One oo ooo <co One o> o ο ζ ο ο ο ζ ο ο ο ο ο ο ο = ζ ο ο ο ο ο ο ο 2: ο ο ζ

SE O O O Z O O O O O Z O O O O O Z O O Z O O O O TM AO

SE OOOZOOOOOZOOOOOZOOZOO OO

 o o o z o o o o o z o o z o o o o o z o o o o o o sr o o o o

. ¾ π 58

ο ο ο ζ ο ο ζ ο ο ζ ο ο ο ο ο ζ ο ο ο ο ο ο ζ σ

ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο ο ο ο σ ο ο sss ≡ ssss Miichi

 m m σ σο ο οσ> σ σ σ ο

 r one h

i f t

 ""; One ^;-^;-^; One

 1 1 1 1 1

 One

oo

ο 1 o — ^l 1 1 mo 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 oo

1 5 oo 1 1 1 1 1

z o o o z o o z o o z o o z o z o z

two

o o

 — ^ O o o o o o o o o o oo oo

 0 00-^ J C) Jl ^ CO h —

 ― '' One 'One' One 'One' One 'One' One '' '' '' '' 'One' One 'One' One 'One' One 'One' One 'One'

 z z zE; s si 3Z Z Z "O" D "D" 0 "o ~ o" o m m m m rn rn rn

1 1 1

C CO CO CO O

 — ^ O <o o <o to o <o — *-— ^ o o c o co <>

 β 1 CO CO CO

 o o <o o CO

One one three one

 1 1 ^ o 1 1 1

 1 1 1 1 1

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

Ii ii Mi 00

ζ σ ο ζ ο ζ ζ ο ο ζ ο ζ ο ζ ο ζ

oo oo oo "-- « i ^ o¾ o¾ o¾ o¾ o¾ o¾ o cj> cj o> n oi ri ri ri ri i cri n cri ^ 4^ 4^. 一 o — ^ o co oo ji ^ c h — ^ o co oo -*J o¾ ri ^. oo h — ^

oo oo oo "-« i ^ o¾ o¾ o¾ o¾ o¾ o¾ o cj> cj o> n oi ri ri ri i cri n cri ^ 4 ^ 4 ^. One o — ^ o co oo ji ^ ch — ^ o co oo-* J o¾ ri ^. oo h — ^

^ o o o z o o z o o o z o ^ o o

 on ^ n ^ c¾ σσ c¾ c¾ σσ

 One fs ro one r one rs3 one

 ~ Ό Ό ~ Ό ~ Ό ~ Ό

 rn \ — Γ― ~ ― Ό-Ϊ— One ~ 0 ~

 Ϊ— One r ~ One T— One r ~ One -0

 i— ^ σ ^ ο ^ σ τ τ τ τ

 cz mm rn rn m rn mmooooooo oo oo oo oo oo oo oo oo oo oo oo co oo oo oo oo oo oo oo oo oo oo oo oo co co oo co oo oo oo oo oo oo oo oo c ^ ai nnoi n oi ji ji-^ j ^ A ^ c ^ AJ ^ ^ cccccrrhhhr ho

IIIIIIIIIIIIIIIIIIIII IIIIIIIIIIIIIIICC OO CCCC CO OJ CCCCCCCCCCCC) C OO CCC 4 ^ C 4 ^ _ ^ to po-«jj cj n ji oc cn o¾ --- 1 ο <° ^ ° °°> ι i -t ^ n ι o oo co ooc en oo ichi ichi o ^ j oi to oo hhoocr oo cn ooc cj oo

ro 0 1 3 3 σ¾-J ri o O " ¹ "--JOO ho

I 1 I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

00 CJi ^ ^ ^ 4 ^

O oc to oo oo occi oo "-J o o¾ o¾ no cn oi 0 0 ー ^ | ~« "ー ー 0 ー 0 ^ ^ 0 to irc ^^ O i--J cn ~ ^ o i cn oi cc oi Oi ^ o oi o one hor o¾ "^ to-" kn one — * o one oo oo-»j oi o oo h oo c cn oo one ho> ^ J Ji" ^ o> o cor one oo oo ro o ai tD oi O "^ oo cn o i o¾ cn co *»-jhoc oi o ji i oi A oi c — * · i o> coo>

ο ο ο σ ο ο ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o ro σ> i ^ w — ^ OT r ji ^ o oo c oi r r oi Oo co o ri oo oo r oo cri i co r 一 c _^>

ο ο ο σ ο ο ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ooooooooooooooooooooo ooooooooooooooo ro σ> i ^ wo oo c oi rr oi Oo co o ri oo oo r oo cri i co r one c _ ^>

^ o o z o sr o z o z o o

i ooooooooooooooooooooo ooooooooooooooo

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o C C C C C C C C C C C C C C C C OJ C 3 C C CO CO

 »-R co —-^ oo oo oi cr oo —»-<oo o — ^ oo ^ -j oo n — ^ oo n oo co — »· σ¾ οο <ο ^ οο οο ο o oo roo oo c — * -noo — ^ h oo hc ^ j ^ os oi h — »-h" "--1« ■ «■ ^ ι one h to one ι οο

Ο Ο Ο Ο Ο Ζ Ο Ο Ζ Ζ Ζ Ζ Ζ Ο Ο Ο Ο Ο

oo ai c o io r o n n r r> 一 o oo on ai c to 一 co o o c ^j ^J O Ji oo oo ai r 一 c oo D c ai co co co o oo 一 ai o¾ r r o> r ro a¾ "^ oo a> c oo 3 ~*" ^j oi 一 σ¾ oo ^ *»j a> co c o c o> oo 一 c o r cT> co ai c o ~«" 4^ 7i 3 一 a¾ ho 一 ro --- 1 4^ on o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o σ> oo oo -^ σ> oo i ^j **J n ^j -^ <o — ^ <ο σ> σ "-ο οο ο οΐ ο ^ οο ο <ο -^ΐ ύ θ ο ο οο ο n o ^J Oi 一 r »- <o — ^ to -^ oo r o ^ co o rsa ji oo oo n co oo co ri o o oi — *- cn o o oo σ 一 oo r n j^ 一 oo cn < cn oo ^ o oo a¾ c oi 一 一 r cn co c oo c c n 一 oo 一 o i 3 o¾ an o o o z o o z o o o o o o z o o o o z o o c o o o z o o

oo ai co io ronnr r> i o oo on ai c to i co ooc ^ j ^ JO Ji oo oo ai r i c oo D c ai co co co o oo i ai o¾ rr o> r ro a¾ "^ oo a > c oo 3 ~ * "^ j oi one σ¾ oo ^ *» ja> co coc o> oo one cor cT> co ai co ~ «" 4 ^ 7i 3 one a¾ ho one ro --- 1 4 ^ on ooooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo oooooo σ> oo oo-^ σ> oo i ^ j ** J n ^ j-^ <o — ^ <ο σ> σ "-ο οο ο οΐ ο ^ οο ο <ο-^ ΐ ύ θ ο ο οο ο no ^ J Oi i r »-<o — ^ to-^ oo ro ^ co o rsa ji oo oo n co oo co ri oo oi — *-cn oo oo σ i oo rnj ^ i oo cn <cn oo ^ o oo a¾ c oi one one r cn co c oo ccn one oo one oi 3 o¾ an ooozoozoooooozoooozoo cooozoo

 z o o z o z o o z o o o o z o o o z o o σ C5 £ 75 CO 3 C7 C3 C5 CD 3 ΓΠ ΓΠ O £ 75 00> ■ C3 σ £ 75 CO 3 »

 3 — 'r <h —'

 -a -D &> 3 3>> 3>>>> £> £> 0 £} 0 £> 0 £ ^

 oococ c3 / rn mmmmmmm ο ο ooooooooo OO XD O CO CD CD CO CD O CO D CO CO CO O CD CO DDO CO t CO CO ooooooo (0 £> £> <0 O CO CO CO »OO Ce 00 00 03 00 00 00 -J 1 I ■ »I ~-1 ~» I ~ «J Oi en

>

<o ~> i to oo ^ ho Ns oi oo o — ^ ω — * o5 c tn oo c — 'r rva ^ aj o ι σ> 1 at — * ch 1 r ~-i cji cn -J ^ oo oi — '^ Cn ~~ i oo ^ io ji ^ ts3 jn oo 4 ^ e> cn j ^ <o oi-ι αι οι · ^

--One ■-― One ∞ ο One — ― ― One ― ― One ― ― One-One o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

co o -j <ooojj ^ r en jyn rsa cn tsa ^ oj ^ ι σ> oo oo oo oo cji i \ 3 σ> — ¹ I ~ »I o oo c» co ^ io ^ 1 ~~ I to oo co i \ 3 ir oo ior cn to co to σ — ¹ oo oo oo IJ; * — '05 ^' to n cn oi oo cn «oho — '~~ JC is3 0o oi is3« oc ζ ο ο ο ζ ο ζ σ ο ζ ο ο σ ο ο ζ ο ο ο ο ζ ο

謹 2257

AMTO

 z o o o z o z z o z o o o z o o z o o z o o σ en o CD 3 »N m c3 C oo:« cn> m oo 3

 1 r r- c 1 1 1 1 1 1 1> ·--1--> 3-· 3 3> 3 3 3 3> ο ο ο ο & τ> & -α -α -α -α -σ m "r ~" i ~ I ~ I ~ ~ I ~; σ; σ 5θ; 3 "" ~ ~ I ~ m rn mmmm ¾5 a3 33 ^ 3 35 ^ mmmmmmmmo c¾ o c¾ c¾ i75 C5 C5 C> c > £ r 3 »j 3- 3» 3 ^ a5 33 33 33 a3 0 0 0 ooooooooooooooooooooo ooooooooooooooo> oi cn oi cri ri n oi oi jsk _ kj ^ j ^ _p ^ _pk 4 ^ s »c co cowh ho S N3 rs3 N3 1 1 1 1 1

C C C C C C C

cjj cn tn — 'hc co cn cn cn σ> n oi n-1-l oo -j oi oi j ^ cn n oi cn j ^ j ^ A c rsa one o to one cn 1 one 1 rsa o ^{- 1 - 1 o - ic oo} J ^ n rva ^ cji oi oi tNa n on - ^ ^ οο - 'cn tn to o oo cn ccc one h rva c to o co one oo o oo ivs o rsa oo or -oo o cn o-ico exs rvs ja ^ c — ^ cn ocs oj rvj O io oo no oj oo ~-i cn n co co cn o oo rvs cn c

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

 c

 CO cri a CJi ccn ^ -t} | \ 3 r co oor — 'OO to oo oo ~ j-1-icno> cn ej> n rs3-^ oi co -t' Or-^ on o-> -ot D rj ji js r ts3 ~-icoo> o — 'c3 »o to oo 4 ^ oo co or —' 1 cn one 1 r -t ^-lo iva j ^ — 'Oo oo ji ho to h ^ — ^ Co — ^ to-i co o co c ^ co iva oo o — '

> ^ I l oo one o ooo to c one one one cn rc co ri ι «Λ σ> οι ο ^. ^ — — 'To j ^ Oi CJI one one one o to oo

 co rh ~> i co-~ JO h-^> r co ~-1 ^ co ~> ij ^ co rr oo cn oi co — 'OO n to oo o co <* · ~ * · "» ·-"J ~ k 1 0 00 0 0 0 ~ J CT O OO O tO CTJ O-1 Ol CO C3¾ CO — '

— ^ S cn rsi oo -J lva cc tn cj ^ oi oo io ^ r ~-1 co σ> σ> o -ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooo oo aa roccc — ^ o to — 'oo ^' cojs o -JC cD-iooo one c ~-1 σ co O) oo co-i oo oo oo h co -j cn co 4 ~ «i oo oj n <o« o — ^ oo — 'to o —' 4 ^. Oo to o-io s3 cr>-~ j

z o o o o o z o z z z o o z o o o o z o o z o

2291 ATOM

 圖 z o cs z o o o z o o z o o z o

 σ C> CD 3> ΓΠ C3 CT3 CC 3> C5 C5 00> CD £ 73 OO> CD 3D 3> One

 m m m m m m m m `` `` i ~ m m m m m

SO X3-^ O Every single o o o o o o o o o o o o o o o o o o o o o o o

~ OOOO CO 0 CO (£ 9 00 00 00 00 00 00 00-~ J -J-1-1-1 -J "― \ <S) cy> at <s>σ> ooo co <o — ix ) — ^ — 'Co oo oo ~ -j co-σ>σ> J oo <o -J σ¾ —- l aj cc ^ cn un -j cTi us oo'-^ ι i rsD One cTi eo oi co — 'Rh op A oo en-o rsa one O

~

co o> o> 05 CT ji n n cn oi oi oi n cn n cji oi

rs3 — ' cn — ' -- 1 ι 1 co 一 一 一 一 一 一 1 OO 00 00 ~ -J ^ ^ 1 0 CJ1 ^ CTI> tk C 1 N3 0 1 O 1 O 1 O t £> 1 O CD CO--■ I oo tv3-ic — 'rv3 0i oo cn o is3 f> i \ 3 c en c oo o — --- l ui tva one to one one-j-oo oo

rs3 — 'cn —'-1 ι 1 co

 on i ~-io c7i oo ^ .C3> oo co ai 3 (7> oo-i co — ^ ooc co j ^ n cn ^ co j ^ i-1 co co ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ooooooooooooooooooooo oooooooooooooo

 A is M;

 ^. oo h jsk oo oo r — 'Co -— j cn cn h cn ~> ι σ> r en oo tn co-~ J i co o cn one o oo c c one

膽

2327 : 2398 »>>>>>>>>>>>>>>>>>>>>>>>>>>>> ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο ο ο ο ο

s = o o o z o o z o ^ ^ 2 = o s: o o

 m 2394 rn σ c¾ οσ>-ο ο σσ> éc N m c? c¾ oa> Ν Γπ σ Γπ — ^ t

"O C¾ C5 C3 C3 2393C¾ C5 C5 0 D" "" "" ": 1>>>>>: t> ~ l ~ H ~ l ~ i —l ~ H ~ l

4 ^ ^ 4 ^ · ^ * ^ ^ 0 4 ^ 0 0 0 0 0 0 4 ^ 0 0 ^ 0 (1 0 ^ i o one <o one on 2388 o o ro

to rj c c c —> ■-«j

r CTs ho c One one "-j

r CTs ho c

 I I I I t I I I I I I I I I I I I I I I I I I I I I I (I I I I I I I I

 > oo cn cA 3 * »

 —

 One 2385 One One

 I I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 I I I I I

 1 1 1 1 1 1 1 jsD 1 1 1 i ；-^

^ -j — i- oo co o — ^fc p o¾ r cri rr --j --j '* -j oi o co o5 ho 1 -p ^ an co σ> --- IC ^ OO J-^ J OO O OO σ> οο ο one cn o ^ hc oo oo> oc co 4 ^ «t ^ a¾ one * ·" · ί ο ο ο ο ο ο ο ϋΐ ϋΐ 3 ~ · Γο one no one ooooooooooooooooooooo ooooooooooooooooooooooooooooooooooooo ooooooooooooooo

^ j oo r A r one an h oo c oo c ^ i ^ c o oo <oo r ^ J one r oo o o one σ> one 3 0

ζ σ ο σ ζί ο ζ ο ζ ζ ζ ζ ο ο

2633 B

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o s s s s s ≡ s ≡: ≡ s s s ≡ ≡ s s s s s s s s s s s s s s s s s s B

 B

 : ^: ^ ^ ^ · ^ ^ ^ 4 ^ 4 ^ 4 ^ ^ · ^

 C ~ O C "O C" Ai C 'ho h rsa ho h r r r r r r One O O O O O O O O O One O CO

Oo oo --- 1 σ> cn ^ cr — ¹ o ^ — »-o oo -i *-o B --J 05 n

 B

 B

ro ro ro h ro ro ro h ro ro h ho | \ 3 ro ro ro ro h ro

 O CO O O ro r r ro ho ro h r h ro h h o O o o o o o CO CO CO CO CO CO

 B

 1 1 1 1 1 1 1 1 1 1 t 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 O CO CO CO CO CO B 1

 O O CO oo

 ooo CO o CJl σ> σ¾ «-j 00 CO o CO CO ro CO CO C CO rsj h C cn oo σ¾ r ro Jl σ> 00 <B> oo o O o ro 1 CD h CJl ^ 1 O ro Jl ΟΊ o --- 1 cn hr-^ j -JO CO cn cn oo cn CO oo OS 1 oo ■ 1 OO CO oo ^ 1 σ> O oo oo oo CO h σ> CO oo tn o ro o ro oo ^ 1 ho ro h CJl O> σ> O oo

 B

 I 1 1 1 1 1 1 tt 1 1 1 1 1 1 1 1 1! 1 1 1 1 1 1 1 cn CT! Cn CJl cn CJl Jl nnn cn cn cn! N cn Jl CJl CJl CJl CJl cn CJl CJl ai cn an on cn

CO CO CJl "-1 ^ -j oo 1 σ¾ cn <> n -t ^ cn σ σ> oo CO o CO oo oo CO r σ> oo -J

 B

 ""-«1 o oo --- 1 CO o CD CJl CO ro oo" "--1 h Jl oo" "--1 o CO o oo o CO GO CO CO cn ro CO on cn σ> σ cn cn C7 o CO O oo σ> ho oo ho C CD CO σ> cn o CO OO

CO ^ -J n 4 ^ r> o 00 o ro — 1 CJl ro r -j> CO σ σ> ro cn Jl Jl σ> σ¾-»j o CO CD

 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1

 -f ^ CO h o o o o o B o o CO CO ro ro CO CO 4 ^-| L 1 1

 ro σ¾ 1 o OO OO o

CO σ> oo PO o σ> CO CO o σ¾ O oo cn O ro σ> OO oo r ro ho oo 71 σ> h O CO cn CO oo cn ΟΊ C h σ> oo oo O CJl ^ ro o σ> oo O σ en Jl o Jl -j CO ro σ¾ OO o σ-^ j oo cn oo OO ^ CO cn CO CO oo σ¾ CO CO

 B

o o o o o o o o o o o o o ο o o o o o o o o o O o O ο o o o o o o o o o o o o o o o o o o o o o ο o o o o B o o o o o o o o o o o o o o o o o O o o o o o o o O

 -^. CJl cn cn cn ai Ol ai σ> CJl σ> σ> CD σ> σ> σ σ¾ σ> σ¾

CO CO CO Jl CO ho h σ B> Jl CJl oo σ O CO to h O σ¾ o CO oo on CO CO O oo cn 1 oo oo 1 o CO CO O O ro O Jl ""--1 σ> TO CO cnn CO CO CO σ> oo cn cn o cn o CO CO O on cn ro CO ai CO

 B B B

 B

o o o o o o o o ο o o o o o o o

 B B B B B B B B B B

CD PRO B >>> ooooooooooooooooooooo ooooooooooooooo

 z o z o o

r* ~*" h 一 一 一 一 ι— ι— ( 2465― ι— r- ^ ^ r^ r^ r- !- Γ~ Γ" Γ~ Ι— ι— ο ο -σ -σ -σ -ο -σ -σ -σ 「 「 「 m m m m m m m m ~< ~< ~< ~ ~< - < ■< ベ べ 「 「 「 「 「 「 r~ 「 「 ェ ェ ェ ェ ェ 工 ェ o o o o> o¾ o> o> o¾ o¾ 05 0> oi n i oi oi cn cn cn ^ "^ co c c c DD> 2466 σ σ σσ · Ν ΓΠ Γπ σ σ r

r * ~ * "h one one one one ι— ι— (2465― ι— r- ^ ^ r ^ r ^ r-!-Γ ~ Γ" Γ ~ Ι— ι— ο ο -σ -σ -σ- ο -σ -σ -σ "" mmmmmmmm ~ <~ <~ <~ ~ <-<■ <Be """""" r ~ "" ェ o ooo o> o¾ o> o > o¾ o¾ 05 0> oi ni oi oi cn cn cn ^ "^ co ccc

I I I I I I I I I 2461 I I I I I I I I I I I I I I t I I I I I I I I I I I

 * ^ 4 ^ 4 ^ ^ J ^ 4 ^ co oo 1 o * — *-o co o — ^ o co o oo o ^ o ^ I σ σ> 1 cr> r> c ho cri o)-^ j oo oo cr ^> — ^ c

 2460 ^ o --j ^ »-j o r 4 ^ oo cn cj5 o c o

O 3 0 o ro n CT> o "-1 _ ^ c cn oi i o απ αΐ ^ -p * .r h h co« l oi o n oi c i

 oo --- 1 co — ^ ^. c ro σ¾ ι σ ο one co o> one

I I I I I I I t I I I I I I I I t I I I I I I I I I I I I I I I I I I I

 One crcr 2458c o one c co cri A cn oi oi c cn j ^ oo one ono> rsD O> -t ^ — '-^ cn oj ^ h — ^ Oi-^ J to co c oo -.j ^ i ^ J Ji CJi nc -J n <o o¾ nco o¾ co n σ σ¾ o oo n co o ― — ^ co h-^ j-^-^ j -t ^-^ co 1 σ> ro ^ i <o — »--« «¾ σ¾ οο Γ ο σ οο <ο <ο ^ σ> ο <θ 3 1 245 r -j — * cni ^ o ri oo nh --- -i ^ <o — ^ r co o <o

co co ΓΝ3 ςο 245 00

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4 250 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ji ji cn AAAAA oc

Z O ZE O Z O Z O Z O O Z O O 245c oc oo oo oo oo oo one o one

ZO ZE OZOZOZOOZOO

2435 3>

 o o o o o o o o o o o o o o o o s s o o o o z o o o σο 3

 r> One — 'o—' 3 · ϊ ·> · · ·-c c c c o o o o One 'One' One 'One' ― 'tJ tJ ti -O TJ T -o m m m rn m C C C C C C C C C

c ^ i oo -j -i^ n — ^ οο σ> οο οι — ^l O¾1 o 1 o 1 ooooo ~ 1 oi-»j oi 05 0¾ co cn oo c o¾ o> oo cT>

c ^ i oo -j -i ^ n — ^ οο σ> οο οι — ^l O¾

CD I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

oo 0 0 0 ^ 0 00 0 0 0 ^ 0 0 0 0 ^ 0 ^ 0 0 0 4 ^ 0 0 ^ σ one hc> ^ an o¾ oo co <3 ro one oo oo co r;- oo | \ 3 One c σ> co ^ o-^ n — ^-^ ri oo -P ^ — ^ r — ^ ccr — i-^ jo o¾ r r5 ""--1 σ¾ GJ r · — ι co- -1 hn ^-o co onr ""--1 o co nr> o -J c I OO CO OC ^ T oo cnoc ^ j ^ cr>

4 ^ O t — i- oo cri o ^ oi ^ a D h co — ^ ^ ^ h — ^ σι — »-ri ro c o c o ji oo oo o oo ^

<ji 4 ^ cri o¾ ^ oo <ooor cj p N3 — »-0 <0 — ^ — ¹

^ I co oo ro o O 1 oi h-«J ^ -JA rND h i n os n cn i ^ oo oo no-^ <o¾ ^ J o>-^ oo oo noo-« jn ~ »" 0i oo c * 3 0o o5 co o ai oo> cji h o¾ o 4 ^ cji tr »» »j * ^ j ^ j cn —»-oo o ¾o co Γ Γ σ¾ ο σ σ — »-oo co — ^ o ^ ro cn oo os — ^ h oo n cn oi-^ hoooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooo

O OO --J one one one one oo oi one o one c ^ n * -j <h o¾ oo ^ jnc one! ^ Rrcc co one i Go o — ^ y 0 -C ^ r -P> »1 απ αι no> oo "-ion ro oc oo o>o> h oo ^ o — ^ -P ^ Γ ο one o> rc oi c one to co o 1 co co co io> hh ^ j ^ J oo -p ^ r o¾ oo co or 3 0 oo o¾ ozozzzooozoooozoooooz o

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

o o z o o o o z o o o o o o o ^ o o o o o o z o o o o z o o o co σσ 3 en ^ σ 3 σ o σο j σσ 3 m o

>>> s s s s s m m rn rn rn m rn m m rn c c c c d>>>>>

ccccccccccccccccccccc cccccccc co <o <oo oo oo oo oo oo oo --- 1 "-1"-1 · I --- ι σ> σ> σ σ¾ σ5 σ 4 ^ ^ CC ^ CCCCCCC ^ J ^ J ^ 4 ^ C> ^ CJ CC ccP ^ AJ ^ A 4 ^ ^ ^

"^ coc oo on oo --j an r oo oo n one h ~ ^ oi co --J ^ ι" "--1 c ^" «j cy one cn o> ch" f ^ "-i-^ c oo c ai o -t ^ orn-^ — ^ c ≥ ». r — ^ c ^ —

 I

c --- 1

 O o i oo σ> --- i oo ^ o c o a¾ 05 c n o ho o ^-«* j ho oo — ^ r r c o"-"-1 —»--^^ ι ο οο ο <ο σ> Γ

CO CD OO I Oi O 0-* J OO Jl O Jl "-J 05 COO OO tO O O> ^ J <O ^ CC-^ C ^ — ^ tO — ^k OO ^ J h-1 oo — n oo ISD" -1 o oo "-1 an oo — '-^ ι ro co or> n ^ i * -jcch oo hncr

OZOOOOOOZOOOO SE OOZOOOZOC

1

 ο ζ σ ζ ο

 | — I- I- | — I- I- I- I- 3 SSS 3 SS 3 -0 -D -0 -0 -0 -0 -0 3 »>->-3»->-·> · ·

P ^ A c c co c oo f r p r iNj rsa isi o o o o o o o o o to to o

 twenty one

 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

 J ^ £> ^ <^ 4 ^ C CJ CJ C C C & C C C O C C C C OJ i a o cri r cn o oo —> to * »*» * »

 4 ^. Θ θ σ> — »c ^. ^ Oj oo <oo oo o to — *-1 οι oo σ> <o (o <o ~ 'ho -— ι σ> ο οο ο & <ο σι <ο ~~ ι os ι tn o oo oo ho c «o ^. c <o oi r CO

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

o ^ 4 ^

 CO ~-\ 3 0 00 3 — ^ CO -I ^ O Oi ^ OI ~> I CR — 'tO hr O CO <£ OJ ^ 00 01 0¾ 0> Ji-1 o ^ oc 3> i σ>- ~ j σ> σ> σ> nc 0 ι ού θ ^ οο <ο σ> σ> ο οο σ> oi o to oo cn — 'σ>-^ co o-~ l Oi — ^ — ^ to cn oo io ^ or oi rsa io ^ oi o iva -l ^ o oo oo σ> ~-i cn -j ^ r -i ^ -P ^-(^-(^ c ^ no) n ji ^. ccror — ^ ooooo co o cn ihn oo cx> o) r — oon cn o oo j ^ ^ c oo rrc-oo "-~ ι tss ciroo cn cn — ^ o oo sk oo · ~ ι ο — ^ c oi oo o — ' O co I cn 4 ^ cn — 'cn ~~ ι rsj o ^ i io ai rc cn ji oo o oo ~~ ι ai oo j ^ on cn o to i ^ ccc co ro c co ro rvs rccc

o z o z o z o o o ^ o z o o z o o ο ο ζ ο ο ο ο ζ ο ζ ο ο ο ο ο ο ζ ο ο ο ο ο ζ σ ο ο ο ο 贿 贿

ozozozooo ^ ozoozoo

 1 1 1 1 "" "" "" ""

Cn CJ1 C 4 ^> ^ 4 ^> ^ 4 ^ 4 ^ ~ 1 ^ ~ ^ ~ ^> ^ ~ ^ ^> 4 ^ 4 ^ 4 ^ 4 ^ ^ 4 ^ _> ^ 4 ^ ^ oooo co o <o co o <oo oo co oo oo oo oo oo ι σ σ> σ> σ · ^ -Ρ ^-^ 4 ^ · ^ ^ ^ 4 ^

 4 ^

o oo — »-o¾ o cr! -t ^ oo co o¾-^ ^ ri a> c ^ ^ o¾ cr o> c --j ^, --JO" --j- ^t J ~ ^ o¾ en oo 1 h 1 r o¾ o> co oi o>cT> or-«jo ^ σ ^ ο ο ι oj ^ ho j ^ o ϋη αι υι · ^ 4 ^"*>"P ^ ii ri n an

 o

 roo ^ oontno oo t rs3 -F ^ <"-j <o — ^-^ r-^-—»-^ n --- 1 i ji j ^ oor oo ^ jc A-^ j J ^ o ai oo · * »« Ι one onch ^ JO o «« -j ^ j one co oo> oo one ca co oo oo --JO i cj> r oo no one hr one oj one OJ h r¾ oo co ro> o one a ^ OA OJ oo r D

 I I I 1 1 1 1) 1 1 1 1 1 1 1 1

IIIII 1 1 IIIIIII — * · IIIII * II 1 1 1 1 1 1 1 1 1 1 o o¾ ^ o> ^ io <o oo oo o oo oo oo oo o ^ oo o to co ooo ^ w —> σ¾ Οθ σ> o oo

ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooo one one zoozoozooosoz: ozooo

ooooo

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o z o z o o o z o z z o o z o o o z o

o o o m o o o 「 「 「

ooomooo """

 m m m m '' 2681 '' m

 33 ^ J 33 33--<-<-<3 3> 5 coo o¾ CT> o iJ »oi cji oi cn oi tn tn oi oi oi Ji oi oi oi oi oi cn oi oi cji cri cri cri ai cn n oi n cn nn cn oooo co o co co oo oo cx> cx> oo 1 i ^-~ j ~ j-~ j-~ j-~ j <35 0> cn cn cn ai Oi <3> ej> n cji cn cji ri

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

 4 ^ oi n ji A J ^ j ^ j ^ j ^ A Oi n un ji i ji ji j cn ji on n n oi m ji j ^ A

 --J OO OOOO CO OO OO "-l oo o one oo one o ~ one o one o one o one o one o oo ∞-1 ccn CX3 one« 5 <£> one <3> C one OI C one 00 00 One Oi l OO Oi-I tO OO — 'M OO — ^ «> cn co * k

— ^ Cn oo-^ j ^ o -p ^ r co — ^ n c. ^ C ^. O -l ^ o a)-1 σ> co oo iss o-1 c-i to one co cn o

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

 ^ ^ · (^ ■ ^ ■ ^ ■ l ^ ji ai un oi ri ui cn ^ ^ 4 ^ 4 ^

CO 4 ^ c cn -c ^ n cr> i oo £> £> co oo c7i-^ chho co oo oo ^ j ^ cn cn-1 »j σ cr to one oj to c I cr> o oo N3 One co en r oo oo one n cji i — 'cn cn <o ^ oo rs3 0> o

CO — 'Jl — ^ J! K OO CJl CO Ol C iO Cn ^ o ho j ^ ~ J Ji o ^ cn CT ^ <o is3-~ JOO — ^ co co co oo ∞ I o--1 co σ> co co co o C7>en>-1 o oo I oo — ¹ oo -jc-1 cn ri one co

CO CO I I icocrc c7> c 4 ^ .- c ^ 1 r cn o O tso la ^ co oo oh co co cs ncr oo cn co ~-i j5k On oo o-~ J c — 'to j ^ o 2671 σ> o ~-1 o oo ¹ ~~ I σ> ^ · σ¾ cn o σ> N3 "-1 o-~ ι co oo one co o-~ i oo o a¾ o <o — 'isa j! ko £> -jc 4 ^ cn <o * k -j eo ro co ro oo oo — 'h rsa ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooo cn oo "-o I 1 00 00 00 00 0 0 0 ^ 0 | ^ | 0 530 53> ^ 00 01 01 | ^ 1 0 0 ー ー> ^ 03 0¾ ai σ> oo oo n co --- ir "« ~ J Oo one cn cji n oo one nor one o oi r one co co co co rooc

o o o z o o o z o o o o z o o z o o o o o z o or o z o o o o o z o o o o o

 Ma

 Ma 1

2651

 z o z z o z o o z o o z o

C5 C5 03> r l ΓΠ C5 00> ■ C3 £ 75 £ 75 03CD CD> C5 00 3>

 One

<<<<<"! ~ I ~ I ~ I ~ I ~ I ~ I ~ I ~ 1 1 1 1 1 1 1 oo oo occoococoo 3>>>> ~ <~ <~ <"<~<~< ~ <~ <~ <"""""" Mmmmmmmmmmmmmm | — | — I ~ I ~ I ~ occocc & o &mmmmmmmm;o;o;o;o;i3;a;o;o;o;o;o;o;o; a 5 C 3 0 O) CD O) 0 0 C> Oi Oi O)) O) O) O) 0) O))) O)>σ> σ¾ cn tn oi nnccccccc co rh rsj r one one one one one one oo AA n A n to — ¹ i ho oh

 oo-1 oo — * — 'an r rs3 cn ^ ^-^ CJ1

 co ^. — 'en oi' C 1 1 σ>-One

 co oo o -l ^ n cri o n 3 o

 I I I I I I I I I I I I I I I I I I

o

 O (£> o co rs3 -c ^ -p ^ cn ι oo o oo co oo r <r <£> CO (O 0> I OO (O O O CO (0 0 — ^ c c

o a¾ j! k C o co cji o cx5 Ji oo c ^ Oi 4 ^. c 'or —' cn to o-^ to ~-1 co c-4 ^ · -— ¹ σ> n oo ^-— 'o -J ^ o 4 ^ —'-i co cn -i ^ n cn cn ncr co — ^ oc co oo co con cn co ho ~-h — ^ oo oo c cn <r> to ts3 — 'θ 4 ^ — ^ ji cn oc — 'Ji oo is3 00 05 0 a¾ o oo — ^-1 ~-i <r> co o —' On c cn ^ ai o ~~ c »n co ~-ich * k io cc — ^ σ> —-i oo cn a> — 'C o oo nr os to oi oo oo cri oo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo oooooooh} & 3 CCCCC hhr CCCCCCOOO & J ^ <_ ^ _ ^ _ ^

 I ~~ ^ ^ o <o »~ i cn oi ~ P ^ ncra> oo co oo oo r _ ^ hir O Na tO iO to ron isa n oo c tri is3 o to ^ a¾ oo oo o cj> o ^ J r ri to cn oo n ~-1-l oo c Nj to o — 'rso o 1 oo ozo zr zoozoooozoooozoo

o ^ o z o o z o o o o z o o o z o87 Resolution 26

o ^ ozoozoooozooozo

CD 3> CT5 C75 CO 3CD 5> C CT CD 5 O CT3 D 3

 t one r one ro —> ■ r — * ■

 m m m m rn rn rn rn> rn m m m m in m m

^ ^ ^ ^

 j --j> <> y> o> o> o>>> o¾) σ¾ σ¾ σ¾) r> o¾>>> o>> o>

 O O O O O O C CO CO OO OO OO OO OO OO CO --- 1 — I 1 --- l »^ J-* J O> 0¾ CT 0> 0> <3¾ CJ> a¾ Cri Xl

I I I I I I I f I I I I I I I I I I I I I I I I I I I I I I I I I I I 4 c c c c c co c c

o O o oo "-^ i -jo ai cn an ¾ OO OO"-1 CO 1 οο <σ> σ¾ αι 1 oc ro oj c ho 1 oi oon 1 ocoo rj — ^ rj ^ no co o ji r co co rh oo — ^ j ^ c oo xD O ""--1 — ^ ^ -f ^ 05 n o¾ oo hoo to

One

* ^ i

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1, IIIIIIIII oo σ> ^ I σ o> oo <oi o¾ cn nn one cccrroc one ro one o oo co o5 ai o¾ "* J oo oo oo o>-^ ji N3 0o rro <oo> o¾ —» «ι oo o co l oo oi r one"-* · one ο ^> σ> one one r cn r os oo r co co oo --- i oo ^ oo one ο οο οο σ ^ one r one o one ^ o oo ro --j one oo o ■ ^ <ο σ¾ σ> · ^ <ο σ σ ο ο oo 1 《^ o cy> co σ¾ o ι — »-oo r oo c * ^ j — ^ ooooooooooooooooooooo ooooooooooooooooooooo oooooooooooooooooooooooooooooohc ro rrrc ro rrcc ro ro ro rrr ro hr ho hcc ro r ro r ho

^ 00 0 00 <D OO ^ O OO OO OO rsJ CO ^ C tN3 CO 0 ^ ^ a¾ ^ Jl J1 0 00 ^ ^ OOO CD 0 00 * ^ 1 00 n ro oo h ■ --- ι σ¾ one σ> σ> One ">> One oo One co One One ■" -jc ai r oo One 0 One oo o cji roo oo cn ccc --- One σ> οο oo ch co o-«icoc oo ncorr> Ο Ζ Ο Ο Ο Ζ Ο Ο Ο Ο Ο Ο Ο Ο Ζ Ο Ο Ο Ο Ζ Ζ Ο Ο Ο Ο Ζ Ο Ο Ο

o co麵 ooooooooooooooooooooo ooooooo

o co

0 2 0 0 0 0 0 0 0 Z O O O Z O O O O O O O O Z O O O C3 0 0 Z O O O O Z O

3 σ co 3> m m σ c¾ σσ 5 oa σ σ οσ>

 O C5 C¾ C¾ C5 C5 0 C5 C¾ O C5 0 C5 "D" 0 ~ 0 "0" 0 ~ D -O>>>>>> α: ^; σ; ο

i> mmmmmmmm ~ <~ <~ <CT C CZ CI CZ CCCC: OOOOOOO: J>>>>> oo oo oo oo-^ ^-«J o c7 no> ri cri cn ι σ> · ^ ο · ^ οΐ ϋΐ σ ^ σ¾ ^ nccccoo σ¾ oo c oo ho cj) co> — ^ hc ι σ> σ¾ σ¾ σϊ ι --- icc co oo ho o oo o -P ^-. 4 ^ o one oo—¾ one or ^ -^ o―o 1 co co 4 ^-"-1 en oo ι co — ^ 1 '—»-^ -j ^ r D oo o ^ o --j <oo-^. r ho -J "" " ~ CO O

 (I I I I I (I I I I I I I I I I I I I I I I 1 I I I I I I I I I I I I 4 ^ C 4 ^ ^ · ^^

CAi chroo-^ o cn-^ nno> o>-(^ oo> o>-»icj ^ chhrcj ^ ^ c en co o Ο σ> ι ^ co io cri ho -ϊ ^ οο — ^ oi oi o — ^ <ο <ο σ-^. ςπ ο οο --- i ho n co

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

 r "-* r r h 3 o r r r

c o c h ho < o o o o can σ¾ "-1 σ σ"-ι σ¾ --- 1 n σ¾ l oo oo c

coch ho <ooooc

<o σ>->>> i ^ ^ c ji c c7> ccoccc ^ an o oo o3 Ji --- jrr cn c fs3 1 <co r ^ hr O ^ J 00 O Jl ^ C0 O> 01 C 0> 0 00 0 0 "| ^ 0 0« ^ ~ * "^ 0 ^ 0-» ^ 00-»0 ¾0 co c on ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooo a¾ oo oo o¾ o> i oo oo o oo <o <oo <oo > ro co oo oo c jJi cn rccoon o¾ ro <o oo oc a¾ ai r ^ j ^ j oo o oo co oi <o oo ho ohoocc co c oo 0 0¾ 0 00 01

zozozooozozozo

o O

I

o¾ oo o> o oo 1 oo co oo o c c σ ο o oo ««-j

CT> oo r o --J O o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o ooc o> o

o¾ oo o> o oo 1 oo co oo occ σ ο o oo «« -j

CT> oo ro --JO ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooo

 ccc co ccccccc co ι ρ ^-^ ^-ο jji o> n oo ri co to ji r oi oo oo c ^ ^ oo-^ oi oi ca ^ ro co co oo oi — '■ ri ^ oi oo r ι οο h o¾ oo oo oo c ai hoho oo oo oo o 1 co <ooo>

ο ζ ο ο ζ ο ο ο ο ο ο ο ο ο ο ο ο ο ζ ο ο ο ο ο ο ο ζ ο ο ο ο ο ζ ο ο ο ο

279544-

 Z 0 0 Z 0 C5 0 0 0 0 Z 0 0 0 Z 0 Z 0 Z 0 Z 0 0 0

cs 3> oon co ΐ σ C5 C5 oa s oo 3 »σ mm σ

cs 3> oo

[<1 r> 1 1

 £> <<<<<<<>> 3 3 3> 3> "0" 0 "0" 0 "0" 0 "0 Yeah I Ye: Yeah: E>>:» I ~ 3 »3 »3>» 3 »3 3» C «<y5 CJCO CJ O a3 3i ^ 3 ^ 3 3O 33 a3 One-one-one-one-one-one-one I ~ I ~ I ~ c = I-" r ~ I- I ~ I ~ I ~ I ~ -σ -σ -α -π -α -Ό -Ό -Ό θ θ θ θ θ ο ο ο ο ζΛ ο-3 »· ϊ»

∞ οο ∞ ∞ ∞ ∞ ∞ ∞ ∞ ∞ ∞ ∞ οο ∞ ∞ ∞ οο ∞ ∞ οο ∞ οο οο ∞ ∞ ∞ οο ∞ ∞ ∞ οο οο οο ∞ ∞ ∞

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

1 oo oo to i oo <oo ^ ^ www co co ccco »cri ^ ui c — ^ rsa o — ^l O — ^l iv3 r ^ c rs3

CO 0 1 C-1 OJ OO o

co <o oj <35 -ti. Ti 7) C ej> CT> —J cri rs3 0¾ oo oo o

co <o oj <35 -ti.Ti 7) C ej>

 oo ω co O CO oo C C CO C • I ^ A <pk ^ ^ (^

 00 — I co oo r CO o OO CO to to o CO O o rsa h \ σ> a> (Jl 4 ^-n σ> σ> -J

 oo co ho rr oo to oo oo co oi — 'cn ~ j «-j ~ j oo oo —' 0» cn rs3 0o ~-1 ^ — 'o σ> to j ^. hro 1 ~' en o oo o¾ en ~-i rva oo ^ o rsD co co oo — »o-lo cn r co —

 — '0 »0 0« 3 01 <3> 05 00 —' OO — 'tn — i

 O O * k CO J ^ ^ ~-1 One H OO OO One C One ~-1 05 00 00 0 One tO O

~ J 03 ^ J n 05 0i OJ O> Cn O> Jl C J ^ J ^ CJ> ^ J OO OO OO CO CO OO tO OO OO Oi 01 CJ> «3 O

O —J tn-1 -J-i ri cn jik on -P ^ oi (o rv3 C o ji co oo un 1 o oo-i cn -JO n — 'Oi c cn j ^ ^ Ji ~- ι σ> θΊ θ one en-J tn io oi c one-ir ~ j oo ^ j> j ^ oo — ^ cn ~-l oo en o oi r tn o one isa ~-1

01 0 0 One O O OO O C CO O Na O On OJ A J ^ Oi CO iO Cn C OO One iO ~ J CT> 0 00 ^ 0 00 tO One o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

CCJ ^ A 4 ^ ^> ^ ^ 4 ^ A> ^ CCCCC ^ CCO r O-l OOO t \ S 4 ^ 0n O N3 £ 3 C3-I OO ^ ^ Jl <^ <^ 0> * k JI C CTI tn <3> --- Ι ΟΪ ΟΟ O O iO C OO o — '— ¹ -^--1 ro co oo co o -— 一一 Ni oi co rso oi tn cn to h to r co oi oo en to to n -P ». c oo coo o5 ~~ I n oo o oo oj *" One o> to One ■-icor co -i ^ -t ^ cn 1 oo -jo — J

z o z o o o o z o o z o z: z o c3 z o

謹 2836

1 IIIII f III 1 IIIIIIIIIIIIIIIIIIIII IIII 0 CC ^ CCCC C0 4 ^ 4 ^ 4 ^ <^ 4 ^ 4 ^ 4 ^> o> oo ^ o oo cD oo o co o ^ c rs3 ^ cr ^ o ^ rcc oo hc- ^ ^ cji noo> oo 1 --- 1 σ> σ> O cn oo C cn cn y> ro ro O cn σ> CO σ¾ CO 4 ^ o 4 ^ on O oo TO σ> ο σ> h ho ohh < y> O an n OO o cn σ> σ> roo cn -t ^ h ro o --j CO h CO »-j-» j oo O CO o oo o cn -J n O CO CO

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1

CO C O CO CO CO CO CO O CO CO CO CO O CO CO CO O O C CO CO CO CO CO CO O CO O CO CO O O CO

σ> <y> oo σ> σ> ro O CO n cn σ> O o oo -J oo CO OO cn n -j oo PO cn oo CO CO h ΟΪ n OO -J σ¾ σ> σ> σ¾ o oo O on CO oo o-^ jo

Ο oo <> CO CO cn CO O oo r> o oo CO CO ro rr σ CO cn οο -J ro oo O CO CO CO CO σ¾ o o σ¾ CO CI CO r cn σ> 05 <o o σ> O CO

1 1

 σ¾ CO cn σ¾ oo h 1 <y> ro O n ho σ> CO oo cn o cn r oo oo CO CO CO ho CO σ σ> ro ho o σ¾ ro o ^ ho r —J αι oo σ ro oo o cn o O ro OO σ> oo o oo cn cn <Ji OO no ο o O ooooooooooo O oooooooooooooooo O ο oo ο o Ooooooooooooooooooooo ooooooo O oo ro rh ro ro ro ro ro ro hh CO r CO O ro ro O CO OO CO OOO CO o CO oo σ> σ> oo CO CO o oo O oo CD CO CO CO CO CO oo σ> O oo oo σ> o oo oo oo σ> o CO o¾ ro oo ro o OO σ h oo cn o OO σ >

CO oo oo n on CO CO CO CO CO O 1 ro CO cn 4 ^ n o oo σ¾ h ro cn cn CO

o o o o o o o o o o

MA GL ATO 2. UB 186867 OOOOOOOOOOOOOOOOOOOOO OOOOOOOOOOOOOOO

 CO O O O CO <to to O O CO CO CO CO O O CO CO O CO CO CO O CO CO O O CO CO <o cn -P ^ .- P ^ CO C C CO CO CO CO CO h ho r> 3 h ho o o o

1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

 CO CO CO CO CO CO CO-^. CO CO CO CO CO C CO CO CO CO CO CO CO O CO O CO CO CO CO CO o ho ""--1 oo o O o CO n cn OS oo CO <£> O CO ro o O oo oo σ¾ -J σ¾ CJl σ¾ cn

<y> CO CO CO h CO • ^ l C σ¾ r cn n cn h Γ CJl n o ro oo 1 o CO

 CO 1 σ> C CO CO cn C CO ro cn oo ΓΟ CO O o O '1 h o oo o ho o CO ho cn ro σ> CO CO cn CO CO ho oo 3 cn ^

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

CO ^ O CO CO C CO CO CO O O CO CO CO CO CO O CO CO O CO O

CO CO oo O oooo oo <y> "-1 σ¾ --- 1 σ> oo" "--1 σ> σ> σ> σ> ^ CJl no oo o CO ro ro oo σ¾ CO CO CO cn O CO ho σ¾ oo CO oo ro cn cn ro ro ro ro

 OO ho CD on ro CJ1 σ> ro CO o σ¾ O CO CO o σ> CO ro ""-«1 o CO CO ro oo cn O <> o --- 1 σ> ooo CO CO ^ σ¾ oo σ h CO cn

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 3 ΓΟ ro r ro ro r ro ho h h h h h h ro ro ro

CJ1 σ O CO 1-«j cn O ro ro ro ro oo oo O oo oo o oo σ¾ 1 σ> O r CO σ> o CO cn ro CO ro oo ro CO σ¾ cn CO oo ro cn CO n cn oo o oo oo σ> n CO ho CO oo oo oo σ> CO cn CO o ro oo o σ¾ ro o O o ho oo σ¾ 1 Ol oo a> o ^ oo oo σ> o CO CO cn oo CO CO σ¾ o "- j Ol oo Jl 4 ^ CO CO cn

O oo O ooooooooo O oo OO oooooooooooooooooo O ooooooooooooooooooooo ooooooooooooo oO cn J1 CO CO CO CO CO CO OO CO CO CO CO OO CO CO h C CO CO CO CO ro o CO ho o cn CO o ho o ΟΊ ^ 1 i CJl σ oo CO CO CO CO O o CO <O o CO

CO oo o o CO o J1 CO CO o CO CO CO to 1 ro ro ro cn oo OO o O ro 1 oo cn cn h cn no o CJl oo CO CO cn O O

o o z o o o z o o o z o o o o z o o o o z o o o

2903 CA ALA B

 Z O Z O 5 30 Z O O O O O O O O Z O O Z O O O O Z O O O O O O O Z O O O m rn o o CD 3 mm o CD 3> c c cr> CXJ 5> σ σ c¾ CD ^: t r one r r one ho one r one

o r o¾ 一ji oi n oi n an on ai ji ui ji n ji n ji un ji ji on n ^ 4^ 4^ --J OO i o¾ o> oi ^ c 一 co c c 一 一 一 o o o o co o oo oo oo oo oo --j o> n cri 4^ oo 一 -«j n n ^ ι oo ·■ l o co r o o oo — *· ο ο oo co cr o 一 o c c ·■ οο r ^ 一n c 一 c ^ i oo ^ ji co c r r ^ oo o> oo n σ> en oo σ> ^ i oo n -^i o ^ ^. ^> — *- co > ι on o oo oo -^J O¾ cri o¾ — ^ -^ o oi oo »■ ι οο -— i ^ o n n r> -«j oo r> o — ι -p^ oo c σ) oo oC-¾ O "C"7> O "C" O "C" ¾ C "n C"¾>>>>>>>>" 「「 「「 「C C¾ C¾ oooo oo ccmmmmmm rn m「 「「 O CO CO CO O CO CD CO CO tO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CO CD OOOO o to CO co co co o co cc oo oo oo oo oo oo oo oo oo --- ι σ¾ σ¾ σ> σ¾ σ¾ σ¾ σ¾ σ> ϋΊ θπ θΊ n one r <o

or o¾ one ji oi n oi n an on ai ji ui ji n ji n ji un ji ji on n ^ 4 ^ 4 ^ --J OO i o¾ o> oi ^ c one co cc one one oooo co o oo oo oo oo oo --jo> n cri 4 ^ oo one-«jnn ^ ι oo · ■ lo co roo oo — * · ο ο oo co cr o one occ co crr ^ oo o> oo n σ> en oo σ> ^ i oo n-^ io ^ ^. ^> — *-co> ι on o oo oo-^ J O¾ cri o¾ — ^-^ o oi oo » ■ ι οο -— i ^ onn r>-«j oo r> o — ι -p ^ oo c σ) oo o

-jr> oojro to — *-r ^ n ^ -— incn oo o oo oo c --j cj¾ ri one en o> ohooooooooooooooooooooooooooooooooooooooooooooooo oooooooooo ^ i-I σ> σ σ> σ σ> σ σ lo ^ n oi n oi n ji n ji ^ cc o o <o 4 ^ o> <co ^ ^ o> c <o oo ^ ^ o ^ o> o> ji c ^ o¾ o o¾ cho> oo cc oo r > c ^ j

z z z o o o z o z o z o z o

9 ATOM 293 ooooooooooooooooooooo ooooooooooooooo

 z o o o o o z o o z o o o o o o o o o o o z o o o z o o

― ^ — ^ Ro r ho — ^ — ^

1 1 1 0 1 '305 1'-'' 1 '1' 1 'e''''1' 1 '1' 1 '1' 1 '1' Be Be Be '<<Be Be Be' ~ <''"" One ommm rn mmmmmmmmmmmm ^ ^ ooooooooooooooooooooo ooooooooooooooj ^ cccccc 3003 ccr ro r ro ho rr one " ¹ " one one one one one one one one oooo co co c co αι en i-»j an ai ri o« ^ cri * »j" * j-»j o¾ o¾ o¾-» j o¾ ccnj ^ n --- 1 oo oo co ooo — 7> -F ^ — 3000 i co ri --jo oo or> ro oo oo — ^ orio oo ro ji o¾ ji n --jn ισ¾ c o¾ j ^ — * cj> cn — ^ co o>-«i oo o> ^ o ^ noc ^ J oo o co co> ^-^ c oo ^ c7 ^> c ^ ^ 4 ^ 4 ^ ^ 4 ^> ^ ^ ^ ^ ji ai ni ai j ui n ji <^ i ji C7i oi n oi σ¾ one o> oo oo ji onroohh 1 co oo o 1 — * ■ — ^ "-ih — '■ r cn c co — *-c oi r — * ro-^ oo oo o rs3 i — *. ^ J oo n rs3 — ^ rco oo oo ι σ> co oo on co "-1 4 ^ oo co --- ic one-"-jh co — ^ cn n — * σ>σ> σ¾ ο — 2997 ^ n oo ^ ji nc co h --- 1 oo co ^ onn ι o one

IIIIIIIIIIIIIIIII 1 1 IIIIIII 1 IIIIIIIII One 2995 One oo ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο 2993 ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο οn --- 1 --- 1 oo --- i oo oo oo oo -"« J oo oro one «ι t σ> i-^ jo> *« jo> nr ji <oo oc co 4¾.oor ^ oo ^ o> n ^ oo rs3 ^ ^ r oo o — ^ oo cri ro co ooo — *-<oo oo o ^ J oo r> oo tri σ> -p ^. oo cn — · ■ io> ~ * ^ jo> c ho ro an one co one o¾ oc one oo oo> oi c cn One on co on one

o z o o o o o o z o o o o o z o o o o o o o o o sr o o z o o

2759

 o 3042 o o o o z o o o o o o z o o o o o

3> CD 5 O O CO> ■ 3 σ σ 3 3 ro — ^ r

 "" "" "" G G c c o c c o c "" "" m m m m m m m m "" ""; ；; ^: ^

-<-3> 3>>-· 3 -σ -σ -σ -α -σ -α -σ -σ-<---<c = c <= ccccc-<-<-<-<ο σ ο ο σ

— ^ Ο ο ο ο ο 9ο 303 ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο 7 303,,, hhhrc ro rrrrcr ho hhcrcccc co cccccoo -"-J oo o <o co-^ J oo co o cD oo co to one o to o oo oo one oo one" ^ ccccrc 0 "P *> 3036

C7> CO "-1 o σ> 1 σ> c cn oo --- one o one --- one one oni

 CJi A ^> 4 ^> ^ αΊ ΟΊ ΟΊ αΊ ΟΊ 4 ^ 4 ^ · ^ 4 ^ ^ ^> 4 ^ ^

CO

 co σ> o cn o 1 ^ ι cn on c cn ^ ι oo — »■ oo co oo" "--1 σι oo cn n oo σ> --- one cn

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

 1 1 ^ · 1 1 1 1 1 1 1 1 1 2 303 1 1 r r 1 1 1 1 1 1 1 h r o ho h r r o r

 αι σ¾ one o¾ cco co c cn oo o¾ c ^ j one oh --- ir oo o one o ^ -j σ> oro "-i oo ¾.-^ jo« r-^ oo — »-ci oo oo cy> ^ j> cn o <o ^ j ^ j D cy> oo r * oh <o -i ^ co o — «« jc ai o¾ o¾ <o <o one hO A o> oo ”ho A h * »J cri c one N3 n one o> A oco one oi oo oi ho one ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο

ζ ο ο ο ζ ο ο ο ζ ο ζ ο ζ ο ζ ο ο

 0 0 0 0 0 0 0 0 Z 0 0 0 0 C3 0 0 Z 0 0 Z 0 0 0 0 0 Z 0 0 0 0 0 0 0 Z 0 0 ij rn rn ^ o oo 3 ο 3 Γ Γπ σ ο ασ > ο ϋ οσ 3

 r one o one one one h

 -τ3 -Ό -Ό -Ό ~ Ό -Ό -Ό ~ Ό ~ Ό ~ Ό

m m m m m m m m m m m m m m m m m oo o o o o c o G ^ a ^ O -O -D ^ D tJ -o ^ ^

 I I I I I I I I I I I I I I I I I I I l I I I I n ^ ai oi n n ai ot ^ »^ cn ji n ji n oi oi ji n n oo co oo o r« »»--»» ■ σ¾ o

 cn oo oo co ^ CO i o c co c o ^ oo cn o o <o o cn --- co cn σ¾ cji

I I I I I I I I I I I 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

^ J 0 ^ 0 "^" -J "^ JO <0 one oo one nj ^ oo> <o cn oo i oo ^ n one r one Γ σ¾ σ> σ> ^ ι οο οι one co cn c one θ 4 ^> σ¾ one ooo oo c ho co one "<< j" "J Cji o oo o¾ o¾ ji o ~ *" O h one--j co co o co ^-o — ^ oo co oo l oo oj) One co oo cn oo oo One on One One One oo _c ^ oo co ^ ""-«ι ο One-ooooooooooooooooooooo ooooooooooooooooooooooooooooooo ooooooo oo —»-co ri ^ <οο <ο — »-oo -i ^ o o oo -jrrir oo one--jco oo jj ri o 0 co ooc one _ ^ o * »j one one o one o oo ^ ic oo a¾ oo c ho oo j ^ ο ο ο ο ζ ο ο ο ο ο ο ζ ο ζ ο ο ζ ο ο ο σ ο ζ ο

47 ATOM 30 ooooooooooooooooo ≡: ss

 ^ 4 4 ^ 4 ^

 1 1

 ^ j o oo o n h n oo 4 4

 ^> ι ι cn c3

i

g

nnn oi ji ^^ ccccc ^ ccc co rrhrrr D rr _ <oo --- 1 cr> n -pk cr ~> ■ o oo σ> ncr ~ ^ t oo ι r> ncr ~ »■ o < ozzozooozo ^ orj rn ϋ CD 3> c "5 cr> oo> mm σ c¾ CD cc> cn j- σ

 r one ro one r one one one r

05

 s: o o o o z: o o z o o o o o o z o o o o z o o o

Country

麵 >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ooooooooooooooooooooooo oooooooooooooo

o o z o o o o o o z o o o o o o o z o o o o p o z o o z o z o o o o z o One r> o ro — ^ — ^ ho

 ^ σ ^ σ ^ σ 1 1 1 1 1 1 1 1 1 t

「Ο Ο" "" "" "C C CZ C C CZ C C O O O O O O O C O O C C D O O O O C r h r r r r ro NJ ho r 1 1 1 1 1 1 1 1 1 1 1 1 11 11

 ^ 0 0 0 0 0 <<0 0 <0 <0 <0 <0 00 00 00 00 00 00 00

O O O One o One One * ■ One O O r r 3 h

c o¾ co r cn — ^ 一 h oo 一

o oo --j oo — »■ ho o ^.-^ — ^-« jn-^ joch oo io ^ oo c cri CA5 tD o oo oo o ji <to no

c o¾ co r cn — ^ one h oo one

 I I I I I 1 I I I I I I I I I I I I I I I I I I I I I I I I I I I I! I n o5 ^ l oo oo one o o o o o o one co one 0 <0 "-J" * «J 1 σ¾ σ¾ --- I ^ J OO OO

- oi - * oo oh - ^ io o> - ^ -. ^ - one ^{- - ^ - - ■ - -} - - - - eleven ooooooooooooooooooooo ooooooooooooooo

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

 One "" "-l oo o cp one or one <o one one <rh one jo ^ co r rsa ho c A ^ J — ^ r oo oc oi n 1 co c cn c oo l oi hc ro o oo 1 o oo h ^ ι ^ c — * ■ ^ c

<oo cr -j ^ — ^ ooo oi oo ono 1 σ> oo oo oo i cn oo c oo o oo nzoozozoozoozzzo

>>> o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

O O Z O O O O O O O Z O O Z O O O O O Z O O Z O Z O O D O Z O CD Z O O O

 One

 (— R- i- m m m m m rn rn rn-<-<-<-<-<-<-<-<-<

一 一 一 一 一 一

1 1 1 1 1 1

 I I I I I I I 丄 I 丄 I 丄 I I 丄 I 丄 I 丄 I 丄 丄 I 丄 I 丄 I 丄 I I I I I I ι ι

00 ro co co one jO; — · ■; — «· | ^ [\ 3 o¾ cji o 1 one <o oo

 1 1 1 1 1 "-1« «J ho 1 1 1 1 1 1 1

 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

 One

 D O Oo o <^ o rs3 C o ^ D 00 ^ o ^ o

 o <ooo oo oo oo <o oi n -two o o¾ o¾ ^ r <rsD cri ^ ^ c oo ^ ji cj ^ oo c7> oh (^ jioi <o> <ι o σ> o oo ooooooooooooooooooooo ooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooo One one one

oozooooooozoozooooozo ozozoooozoozooo

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o s s s s s s s s s s s s s s s s s ≡

O

o o z o z z z o o o z o o o z o o z o

oozozzzooozooozoozo

o o o z o o o z o o o o o 'C5 Z O O O O Z O Z O O O Z O 00

1 1 1 ΓΝ5 1 1

 00 One "One Ω" One "One" One "One" One "One">>>>>>>>

 ^ 3291 1 1 1 1 1 1 1 rr 1 ho 1 ^ cchcocor A oi n oi ch 1 ho ^ h 1 ooo 1 ¾ 1> ooca) e)) oo --- j σ> σ¾ ο — ι ^ o σ¾ or ri ^ <n CT5 — ^-^.

 One ^ One o — »■ o ro -p>» --- »-o o o — ^ O OO-^ J

 o> rsj n cj> o n o r n oo 45fc c o h oo Uniform ai oo o 4 4 o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o 3 o o o o o o o o o o o o o o

 I O ** J "-J <OO — ^ JI

 1 1 1 1 1

0 0 0 Ζ 0 0 0 0 0 2Γ 0 0 0 0 0 0 0 Ζ 0 0 0 0 0 0 0 Ζ 0 0 Ζ 0 0 0 0 0 2 0

 ιο — ^ h — ^ h one h

 Five

 ェ: ^ ο; ^: ^; Ό; σ; σ ίσ? Σ: ^: ϋ

CO CO C C C O C C C C C C C C C C C C C C C C OJ C C C C C C C CO oo

_ ^ o c ^ σ¾ 4 ^ οο σ> οο one r o> one o¾ o> one one at one one oo * »j« pk c o oi c5> co ai o

 ^ -J JI oo

 One σ o One one — ^ o ro I o

 I

c — ^ o ji oo o> ^ --J Ji oc-«-j --jo ji ro r — * icr one co r one cn r ^ -jn oo co c ϋΊ 3 θ οο-^ ι <θ"- ^ 3-^ οι — ^ n oo co ^ n oo c3> io> ^ "-j oo ^ jc ^ rs3 — ^ 1 c cn σ> σ> oo ccccccccccccccccccccc ccccccc

o o> o o cn to <o o¾ o z o o o o o z o o z: z z z o o z z o o O ^ c oo ^ c oo rs3 0 oo c ji oo ji 05 co o¾ c ^ io <ooo «o-^ — ^ co to oh a¾ — ^ ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo oooooo oo σ> co cn 1¾ ao c cn c one a¾ oo r

o o> oo cn to <o o¾ ozooooozooz: zzzoozzoo

ATOM 3299 ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο

 5 0 0 0 Z O O O O Z O O O O O O O Z O O O O O O O O Z O O Z Z O Z 3 0 0

 3366 σσ> σ σ ο σσ> m m σ σσ N N o c¾ ro

 h one r one r one

 3365 「「 「「 「「 「「

"" "" "rn m m rn rn m m m" "" "" "" "";

3363 <^ ^ ^ ^ c c c c c c c c c c c c c c ^ — ^ — ^ 0 0 0 0 0 0 0 0 0 0 o o

no * -J ro ro oc 3360n ri -p ^ — ^ — ^ co o oo o — ^ co — ^ o — — ro — ^ ja. σ> en o en o>-»JO> one σ θ" ^ one "^ I oi oi -J Oo o> o oo o co j ^ c» <o ri ri — ^ ri o — ^ O ho> ri <oh «-j — ^ c ¾. Ri oo <--j cn h 1 1 "^ 1 1 1 1 I i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i III III III 1 1 1 ooo oo <oh 1 1 ro 1; 1 >> 1 ro 1 ^ cr One co co oo one coc A Ji oi oo cn --- io cji h o¾ rh -p * .n -P ^ o -P *> oo c cji i one o¾ o oo one o¾ ro oo one ^ j cn oc oo coci oo crc-»JO one to one oo oo o jsfc one r co o¾ *" »JO" ^ ~ »" C Oi o¾ r ai 0 4 ^ ι -j oo c cn ho to cn oo io — ^ 3357 ι co icor ho -i ^ ^ -j — ^ ¾ »σ> — ^ ^ — ^ oo

IIIII t IIIIIIIIIIIIIIIIIIIII IIIIII oo — * o oo --jooo> n ri -p *. -P ». — * · Γ 3356 ο-^ ςτι-^ ι ooo <o oo oo oo ^ jo oi o one oj ^ oo h oo o one oc 3355o h oi one hc one o oo o oo one one ji co one o¾ o one o¾ oo ro oo crc oo i <co> h oo cj co cJ 05 0 o ai o ai σ ζ> οο ι σ> οο οο ο oooooooooooooooooo 3353 ooooooooooooooooooooo ooooooooooooooooooooo oooooooooooo

 3352 ； ~ ^ jx o¾ jji jcoolo cri ^ -J Oo ji rva ro co o ji cn co A oc one o oo o cn c one o¾ ro one co> ho one σ¾ ~ ^ ic oo co ro> c co o> ~ f ^ o one one ro co one co one oo> one <ο σ¾ σ> οο one ίο οο οο αΐ σ σι ο ^ ο ζ ο ζ ο ο ο ζ ο ζ ζ ζ

3335

zoozooozo zr oozoooozo

N 96 LI 00 I S9S LZ- 0S-039 "6- 39 0 v, v N zm MI01V

0 39 '63 00 I Ι ΌΖ- 198 01- IS 0 mo 0 im 匪

0 19 '63 00 I B 8 `` 98-189,61-m 6-19 0 mD 0 om W01V

0 οε 6S 00 I εβε 'εε- ^ 9 12- 938' 9- 19 0 mo 230

0 39 00 l ^ LZ 'εε- 2917 11- εε8' 8- 19 0 HID 130

0 ZZ • 6S 00 l L fr εε- 28fr 13- 9 O 0 8- 19 0 ΠΊ9 ao

0 B 9 LZ 00 I L9Z., Εε- οζ-60 60- 19 0 ΠΊ9 90 9tn V

0 9Z IZ 00 l 6 6 η- 909 61- 901 8-19 19 go19 goV

0 36 00 l 383 '9S- 002 03- m, 8- IS 0 n, 9 V. KKV

N fr9 92 00 l Lz- 60 60- m O- 19 0 ma N ZZKV

0 99 92 00 L m '8ε- ε03 13- Olfr' 8- 09 0 ¾ 丄 0V

0 0 LI 00 L o '8ε- 8S 02- εε ^ L- OS 0 y

0 08 09 00 l 691 '6ε- ZZL 9Ζ- 9 9- 09 0 m HO OZK W01V

0 U 00 l οζ.0 '6ε- 998-69fr "9- OS 0 y human zo 6 εV

0 ZZ 00 l ε ^ 8 'B ε- L Π- 609 S- 09 0 y Human 丄 330 8 ε mioiv

0 9t 83 00 ■ I S9 B LZ- ζζ- 99ε s- OS 0 y People 3G0 ίΖΠ ■ V

0 69 00 l 089 η-883 9- 09 0 y Human 130 130 εV

0 6Z 00 ■ I 931 Ofr-Lsz τζ- 091 S- 09 0 y Human 丄 Lao s ε 隱

0 LL 9Z 00 I 668 '8S-9'-981 S- 09 0 y

0 66 LZ 00 I 608 '8S- iz- 910 S- 09 0 ϋ 人 丄 90 W01V

0 Z6 "93 00 I οοε '6ε- 9 LS O3- IZZ" 9- 09 0 a person VO WOIV

N 82 '93 00 I 632 6ε-168 '81-'9- 09 0 N ιζ W01V

0 39 ZZ 00 ∎ I QZZ 8i-8 'O- 6fr 0 mL 0 ο ε V

0 ZZ 00 ■ I εεB, 6ε-B 86 B B 9SZ 9- 617 0 yHi 0 z IftlOlV

0 10 ZZ 00 I '-8 '91-931 9-6fr 0 yHi 300 隱

0 LL 00 l 916 Ofr- O 06-966 V- 6fr 0 yHi L90 W01V

0 18 00 l 888 Ofr- m 91- S8S S- 6fr 0 ao 隨

0 03 zz 00Im6ε-8 8 "91-ZLZ" 9-6fr 0 VO s ε WOIV

N 99 zz 00 • I οε ^ 8ε- 83S 91-8SS "9-6fr 0 ¾ Hi NV

0 C8 zz 00 ■ I ε-S8 · 9 卜 3οε L- 8fr 0 Π3Ί 0 t in

0 zz 00 l ΖΠ LZ- 39fr '91-乙 '9 1 817 0 Π 3 Ί 0 z m W01V

0 6 '61 00 ■ I Ζ9Ζ 'εε- οε ι "91- 909 s- 8fr 0 Π3Ί ZQ imoiv

0 93 zz 00 l 990 ε- 368 l \-6SZ. 8 0 Π31 ιαο IN01V

0 99 zz 00 l 162 06-06S,-8 O 9-817 0 n, 60 WOIV

0 30 zz 00I 689 SS- ZZL '-zoz s- 8fr 0 Π3Ί ao 80frS WOIV

0 t? 9 zz 00 l 830 '9ε- ι ιζ-933 S- 8fr 0 Π3Ί VO LOK 匪 COO / Z, OOi8I / X3d 61-T8C0 / 800Z OAV

I I 丄 I 丄 I 丄

 4 ^ oo o r one o o

CO O 4 ^ cn O oo CO oo ro oo oo o cn O CO oo cn CJl CO oo σ> to oo ro CO CJl CO cn ro oo o C oo-«j • ^ j <> CO oo o oo <o σ > <oh CO n oo ΟΊ ^ oo oo ΟΊ o

1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 r ro ro ro t ro ro ro ro> ro r ro ro ro ro t

r ro CO ro C ro CO ro ro o O ro ro CO CO o CO oo σ> 1 ho ro cn CO <y> o σ> σ> ro ro CO o σ oo O o σ> o ro σ>

1 CO oo σ> cn CO C CO CO CO oo oo cn O h CO O n σ> o σ> cn cn CJl CO ro O O h σ> cn o O σ C oo

 1 1 1 1 1 1 1 1 1 1 1 1 I I t 1 1 1 1 1 1 1 1 1 1 1 1 1

 CO CO CO C CO CO CO CO C

CJl CJl n ^ CO 3 O O o o o o o oo O CO ro D O CO CO oo OO

CJl σ> o ro oo ro oo ro CO o 4 ^ o oo CO o O o oo σ> h ro 1 O o> CO CO h CO ""--1 CO o

<> ro oo <n ro CJl OO Ol cn cn oo oo O h ro oo ho ooh oo Jl 4 ^ o CJl ooo σ αι oo oo r CO oo oo oo --- 1 CO CO CO σ> o oo OO CJl ro cn CO ooooooooo O oooooooooo O oooooooo O ooooooooooooooo O ooooooooooooooooooo o ooooon CO O oo OO oo OOOO CO ro ro ro ro ro h ro ro ho hh ro

CO O cn CO σ oo CO CO CO oo oo h oo CO o σ oo cn Ol n cn Ol cn cn ho σ> CO CO CO Jl O> o O CO oo σ> oo o σ¾ oo CO C ho O o σ> oo CO CO σ¾ h oo CO o CD cn> oo o CO CO CJl σ> CO O oo Jl oo σ¾ O CO CJl

o o ◦ o o o 2: o o o o o o z o o O o o o o σ o o

ATM445 0 ALA 2O 3 CA AL AM43 CA 0 sTO 34

z o z o o z o o o o o z o o o z o o o o

zozoozooooozooozoooo

m m en> · m ο CD σσ?> ο on

c o r h — ^ one p r one

 ~ 1 ~ I ~ I ~ 1 ~ I ~ I ~

 ^ σ? ο; σ: σ: ^ 3 = Ό "" "" "" "" "" "One" One "One" One "One" One "One" One "One ~ I ~ \ ~ II ~ I ~ I ~ I <

33 ι è ェ ェ> ο¾ ο>> σ¾ ο> ο>) θ) ο> ο>> ο> ο> ο CD Ο) Ο) θ) θ) ο σ> ¾ σ> ο> ο¾ > ο> ο

σ¾ σ¾ --- 1 οο οο ι οο οο <ο ο —-^ Aa c ro c isa o r rva o o o c ro c αι O ho ~ * o i σ¾ o ^ on oi o o r cn 05 <0 ^

 I I I I I I I I I I I I I I 1 I! I I I I I I I I I t I I I I I I I I I

4 ^ 4 ^ c c c c c c o c c c c c c c c c c c c c c c c c c c One O QO OO OO "-J --J --- ι σ σ 4 ^--» J a¾ ji c c r h o one r one r j ^ c h-^ one

^ 4 ^ ^ i c r — ^-— ^ c o o o o — ^ ri o n

i ^ oo oσ¾¾ n 4 ^ oo r — »-"-«j ¾ r

 ^. n h O O "o o c7> h cn» oo ji cj> — ^ ho o c cn ^ -j n oo

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

o oo co co ^ o rsa one o one rh cn ai cri cri "p¾ | ij 3;-^ one oo c co jO;-one oor jo o ^ --- oo one oo one en co o¾ oi ~ * r ^ I-- i oo ji c oo-^ co>-«j oo oo oo o ri 4 ^ ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo oooooooo ai ji o Ti ai ai ■ ^ on 4 ^ 4 ^

1 ^ 0 oo o> cn oo r o a¾ o¾ o-»j r r o c ai j ^ oo

ο ζ ο ζ σ ο ο ο ζ ο ζ ο ο ο ζ ο

脑

Αϊ h oo

0050.02 C. ATM 3622056023O-1.401649 0050 ATM CG2 00020.7O 0--

0047.73 C AT2B 38211.04850OM 360 C C--

0046.17 C AA 057TOM 3619 C 0

 43. N 46323.88551 0098 ATM 3618 N 0O--0 41924.1452 0045.63 ATM 3617 0 GLN 09O -—

 1424.2 0043.49 C AT616 C GLN C98865OM 31—

 N274 0042.88 AT15 NE2 GLN 2805OM 36 C—-^. -Ι ^ -r ^ -ι ^ -r ^

 2.0042.8014 GLN 6965394558 ATOM 36 C--. 04.013 CD GLN 09026332550396 ATOM 36 C--I I I

 I

 o o one one one o one co o one

 2. 043.0 CG GLN 547676655095 ATOM C--.4 042.1 C11 CB GLN 46025826506 ATOM 360--22 0042, 85 CM CA GLN 42865 ATO C -—

 27.3152 0042.31 N AM9 N GLN 0 9865TO 360—-2.31752 0041.300 Stroke 68 0 A 0 9838301-One o oi io co j ^ c tsa One c oi ro oo ^ — 'cxj co to io rnc ~-ih c28.36952 0041.96 C ATM607 0 AS 0O 31-cn & n cn -j — 'tS3 COOC 1 OO OC ~ J CT OO ~ -JO ~ J ^ I oo .—jnc 4 ^ no co ^ <o-co co> oo oj (£> -~ jo oo-~ j

 130.97550 0042.840 ATM 3606 0D2 ASP 088O--7732.18749 0046.410 ATOM 3605 ASP C 3--50 0043.69 C ATOM 3604 CG ASP 0-7229.90750 0043.07 C ATOM 3603 CB ASP 0 0--C 93929.67652 0041.81 ATOM 3602 CA ASP 0--N 23830.789 0040.56 ATOM N AS C--4.0 67630.9345 003859 ATOM 3600 0 C--4540.08 C 0 65631.313 00 ATOM 3599 C--556 0036.83 CM59 C 89029.60 ATO 38 CD1--4356 0037.32 CTM 3597 87230 7 AO--72.3355 0036 20 C ATOM 359 CG C 503862--1.77054 0038200 ATOM 3595 CB C 5053--0 7832. 0038.58 ATOM 3594 CA C8-. N033.15455 0039 ATOM 3593 NC 50--.700 00391 ATOM 3592 0 GLU

47.30MC 60334.655 00393 ATO 3591 0 GLU--714 00.00TOM 3U C 19435.55488 A590 0E2 GL--91047.720 TOMLU C 93634, 956 0 A 3589 G--046.0TOM 3 GLU 0 096 A588 CD 044TOM GLU 0 63634.55 05.3 CA 3587 00- - ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ζ ο ο ζ ο ο ζ ο ο ζ ο ο ζ ζ σ ο ζ ο ο ζ ο ο oooa \ ~ I ~ I ~ i ~ I ~ I ~ I ~ ι ~ ι

 I- I- I- I---<-<-<-<-<--<-<1ι—one i—one r—m m-<-<-<-<o <o o o rn m m

o o 1 ~> ·-1 r j — j c ho co 1 <o n oo

cn o -Pk 3> <o o o co — ' c n n — <·

cn o -Pk 3><ooo co — 'cnn — <·

 CO 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 r r rss h 1 1 h rsa rva

 C C C CO J ^ Ol CTJ Cn tJl J ^ f C CTl n Ol JI n 1 OO ~-1 00 — 'O O O OO tO O —' h

— ^ Co -l ^ -t ^ σ> σ>-io j¾ —joo> c to — '^ θ 4¾ · ο-l OJ to ^ oo-^ os oi nc-1 c one rcc AJ ^ to -J oi oi cn one ^ ^ icoo one oi eo -j oi oo one

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

 (o o o — ^ n -t ^ -l ^-^ 3 ^ o c c c (o oo ^ isa rsa r isa iva oo-1 cn -i ^. ^ co r co ι

C 0 CO tS3 OOO CT> 01 — '<3¾ -J ~~ I OO 03-l <O-^ (O 00 C3) C (O — ^ OO -t ^ O — ¹ 1 O ΟΠ ΟΪ -P ^ Oi CT>

 O O ~ J o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o c c c c ri n ^ ^ A C c c A n cn ^ n n n n n

4 ^ σ¾ σ¾ — ^t cj o ji cc o¾ oo o -P *> ^ co c o>-^ c — ^ ir ro n -f ^ cji o o> — * * ο ο ο οο σ> ^

One one << one one one zozozozzozozzo

0 93 ΛΙ 00 ι 098 m • o- 812 '9-98 0 311 VO 廳 W01V

Ν 66 \ ι 00Ifr- m z- 996 '9- S8 0 3 1 N S69S I / II01V

0 Ofr 00 ■ ι ε ^-669 l- • 9-178 0 Odd 0 369δ I / II01V

0 98 ιζ 00 'ι ε ^ 9 z-z- L96 "9- ^ 8 0 OMd 0 169S I / II01V

0 • 61 00 L ^ 66 n-9 B 8 ε--8 0 Odd 90 069ε 隱

0 6 03 00 • ι m • ε-391-η 0 Odd ao 689C WO 丄 V

0 S6 • 61 00 ι '-L68 • ε- 839 9- η 0 Odd VO ■ W01V

0 S B • 81 00 ι 609-08 B 9- η 0 Odd QO pulse W01V

Ν 99 ΟΖ 00 ■ ι LC8 6-ZZ 9-η 0 Odd N 989S WOiV

0 9fr 11 00 ιι C9C-218-8 O 0 ■ 8-0 1 VA 0 989δ W01V

0 38 QZ 00ιι 909-198 899 L- ε8 0 1VA 0 霞 W01V

0 ■ 81 00 ■ ι £ 99 "9- 968 • 01- £ 8 0" IVA 3D0 C89S W01V

0 99 ΟΖ 00 ■ ι 896-£ 99 • ε-m • 01- S8 0 ΠΥΛ 190 W01V

0 09 11 00 ■ ι 683 9S I "9-610 0 G" S8 0 IVA 90 Conceal W01V

0 19 QZ 00 ιιεε9 m "9- LZ9 • 8-S8 0 HVA VO 0898 INOIV

Ν 06 ΐΖ 00 ■ ι 988 n- 808 • 9-L2Z • 8-C8 0 IVA N 6B 9ε IN01V

0 Η ζ 00 ■ ι 630 O 19 19 9-Z6L L- 38 0 IVA 0 INOiV

0 68 ΐΖ 00, ι 9εο ε B-810 '8-38 0 "IVA 0 W01V

0 LI 00 ι S69 8 9 01-16S • 9-0 "IVA 390 9 9εV

0 30 9Ζ 00 ι 10B n- 6 0 • 6-ZL6 S-38 0 IVA L90 隱

0 38 9Ζ 00 ι 乙 01 ■ 9fr- 693 • 6-LZ ^ • 9-38 0 "IVA 90 WOIV

0 18 ίΖ 00 ι 931 ■ 917- ■ 8-686 B-38 0 IVA VO ε 9ε 隱

Ν C9 ΖΖ 00 ι βεε LP- ■ 6-0 ii 9 • 8-28 0 IVA N ZL9Z WOIV

0 9 L η 00 ι m 9P- 6 B 9 • 6-309 0L- 18 0 ^ 丄 0 WOIV

0 93 00 ι 9 LS L-s 6-0 B 6 • 6-18 0 H 丄 D ο B 9ε I / IIOIV

0 \ Ζ 11 00 'ι 868 8P- ZL [L- O ^ L 01- 18 0 H 丄 390 699C I / IIOIV

0 86 LZ 00 'ι WO 09- 6 ^ 9' 8- 9S 21- 18 0 H 丄 L90 899S WOIV

0 99 00 ι 088 8P- • 8- C89-18 0 ¾JH 丄 ao 乙 99εV

0 02 00 1 699 8fr-6 B 9 • 6-IL9 0L- 18 0 丄 VO 999S mioiv

Ν LZ 00 ι 8-636 • 01- 6 11- 18 0 ¾IH 丄 N 999C WOIV

0 36 'οε 00 ι 09- 098 u- 661 01- 08 0 311 0 籠 V

0 IS 00 ι CSS ■ 617- ZZ6 U-860 • 11-08 0 311 0 WOIV

0 69 83 00 ι 96S L-919 • 91- 921 ■ 1 G 08 0 3, l IGO 399C 陋

0 1 'οε 00 Λ 9 • 8 m "9 L- 9 ^ 8 U- 08 0 311 I DO 199C I / IIOIV

0 60 00 ι 6LZ ■ ί ει- 109 • 01- 08 0 311 390 0998 隱

z o z o z o z z z z o z o 0 68 ■ οε 00 ■ ι 839, 8 η-6C0 ■ 11— 08 0 J \ 80 6998 WOIV C00 / .00Zai / X3d 6 8 £ 0 / 800Z OAV

zozozozzzzozo

ο ο ο ο ο ο ο σ σ σ ο ο ο ο ο ο σ ο ο σ σ σ ο ο ο ο ο ο σ ο σ σ ο o σ> σ> σ¾ σ> σ> σ> σ ^^ ^ 0 00 0 0 0 0 0 0 0 cr cri ^ cr — ^ oo oo "-inn ^ cr — ^ oo co-ι σ> οι cr one o <o oo --j o¾ cri cr one

o

ro

CO CO r cn I

n z o o o o o z o o o c z o o o o o z o z o o o o co σ>

nzooooozoooczooooozoz oooo

.E CBU 00 — — — ■ — — ■ — ■ ■ — ■ — ooooooooooooooooooooo ooooooooooooooossssss s ≡ sssssssssss

> σ σ Ω σσ> rn m σσ 3> ασ 3

 ί> ― h 一 ― »■

co co co ooc <<<<cccccoooo co <co o co coo CO OO <OC <C OO OO OO OO OO OO OO OO OO --J --- 1 --- J-»j-^ J"- i o¾ cs¾ o> o> o> o o¾ nn

I I I I I I I I I I I I I I I I

 o o r o 1 1 1 1 1 ho c ^ ■ tfc 1 o o — *-c »r o o * -J o oo o5 l oo o o ro o co j ^ r co —»-o r <o — ^

 I oo-»j oi o> o --j ai-« j oi o i ο ϋΐ ϋΐ Α θο αι · *-! O i c co to r co r oi r cn ^ "^ o i oo ncih oi i o ho ^ oc oo co co oo n oo oocr ho i oi oo "^ onro oi cor

C

 oo oo co o oo οι · ΐ¾ * σ i r --j a¾ ro co ~ pk h i to j ^ h i cn ^ j --- i o¾ nn ro <o oo o oo-o-^ o oi-^ jr ^ cn ccc ^ 1 en o σ> — »■ co cn ^ i ^ oo ^ ^ j -JO Oo o¾ cnoo-&.

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

 _ ^ 4 ^ 4 ^ 4 ^ ^ 4 ^ ~ ^ ~ ^ ~ ^ ~ ^ ^ ~ ^> 1 ^> ^ ^ One o o oo "" j o c r r i 4 ^ o oo O o> One oo o One> ^> ^

 oo one ^ oo c one r oo ^ i ^ c oo — ^ c — ^ c r c o oi o> oo c oo r ^ oo c c 4 ^-^ n ^ ^ o

sr o z o o o z o o o z o o z o o o o z o o

two

ο

 o o o o o o o o o o o o o o o o o o o o o o o o o o o o oi cn ~ t ^ A C c c c c c r r r h rND h one-on-one "· * one-on-one o o o o o

I

 1 o o CO

h oi rt ji — '- σΐ ο 1 σ> co

One co o¾ --J to co one n cn o¾ c co hr -j co r --- 1 oo en on

h oi rt ji — '-σΐ ο 1 σ> co

 ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo oooooooo one h oi n one ^ 1 ^ io> —J 4 ^ --J Oo o cD OO h one "-J Oo ai ji o> c oi h 1 co ^ ι σ¾ σ> — o tn-«ic ji coo oo-^ c — * <— *-—" "--io — '■ oo oo ^ j co-^ r ^ ι-en ^ one oo one to« -j «no > One oo ro oo ^ «ι αι σ> οο οο σ¾ <ο ο One oo One ro oo o¾ One oo o¾ cn

O Z O O Z Z O Z O O O O Z 0 0 0 0 2 0 0 0 0 0 Z O C3 0 0 0 0 Z O O O O O

VAL803 CB 3 ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο co ^ ooozoozoooooozooozoooo o

ΓΠ C7 DD 3>> CD 3> C C¾ TO 3> C7 CD 3 O CO

 h one ro — — ^ m ΓΠ mmmm I ~ ι ~ ι ~ ι ~>>>>>>>>>>::: tmmmmmm one i ~ one ι ~ one ι ~ one ι ~ one ι ~ one ι— ~ ι ~ Η ~ ί ~ ι ~ ι → Be "<■ <■ <" "" "" "" "" ""; D ^ o ^ o ^ o: ^ mmmmmmooooooooooooooo oooooooooooooooooo

I I —-l l l l l l l l l l l l — ^ l l

 — »O CD Oi -J O O <D OO -J OO -J ^ -tfc n 05 CJ¾ 00 00 0 0 00 -J

 I \ D ^ J-^ i ro <o oo

 4 ^ · <0 σ-^ 1 »<o

 I — I n r D --- o c — ·

 οσ o r o o ro o co ^ co o o o o c o c j ^ oo r j ^ a> o en r

CO I I

σ> ^

 CJl CJ ^ 00 C0 0 ^ ^ ^ ^ ^ ^ ^ J C7> r 0 0) OCO> CO 0C) 00 OOCC 0) ^ — ^ oo> ^ ro O "-J r oo ~ ^ oo> ro oo oo ho oo> oo one h one ochco cA5 ** J o O 3 cr> ho oo mn one c ro r oo i ji ^ ocr ui ^ o ^ o ^ oo ^ ι tο-t

IIIII t IIIIIIII t IIIIIIIIIIII t IIIIIII cccc _i ^ 4 ^ 4 ^> ^ A ^> ■ ^ ■ ^ cn A o ^ cn cn n cn cn-^ io oo to o one rocoj ^ ccn 1 σ¾ σ¾ 1 οο σ> ^ lo co co co one ooooo oo one oo o ji ro one oo oo oo one ^ ^! 0 one oo o c one ro c c h one o r o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

— Lo oo oo cno jj jj nn ro — ^ or --j 4 ^ c o¾ — ij ^ r co T5 --JC oo c — ^ oo oo o-^ j oo oo <o <o ro oo oo-* j cr> n cji ^ j --- 1 co oo oo "-JOO) on h — ^

^ a>r-^> c ^ ro oozooozooooozooozoooo zoooooo

ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooo oo ^ a¾ oo on c oo on o ^ oo oo o> oo ^ c o5 ji o¾ oo> a¾ a¾ ^ o rv3 --J CJi ^ oo ja.cx3 C3 0 0 I oo oo * «~ J to oo to o5 oco i en ~-ioo on cn -— ι — ^ o oo ζ σ ζ σ ζ ο ζ ζί ο ζ ο ο ο ζ ο ο ο ο ο ο ζ ο

o o o o z: o o o o o z o o o z o o o o o o z o o o o o m c "> OCJ> o σ σσ ^ o D j> m rn C co 3 · m m ϋ c¾ one h one r —» ■

 "" "" "—

 "" "" "" M m m m m m m m ee ye ye "" "" 厂 "" "" "" "

o one o

 »· Ο Λ ΐ -ΐ

 05 o c o cn oo

 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ho 1 oo

 1 1 1 1 1

 1 1 1 1 1 ^ ^ ^ j o5 oo o

 One one one h c an c7 one

 -J -J

 1 1 1 1

 1 1 1 1

 <0 0o ^ c7 c7 o o

oooozooooozoozooooooo zoooooo

 ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo oooooooo σ> oo i oo o> ^ to> ^ o ^ oo ^ o ^ ri on o> o oo <^ co o ^ oo oo r 3 cjir co ji co oo n ^ rso ^ oo ji o ^ oo r> ^ o¾ co ^ r ^ ^ o ^ cji — »■ one oo cji h oo to j ^ oj ^ one 00 00 one << one" "-i oi o« ^ o> ho r <o ^ j one o> o¾ ai ¾ ho>

oooooooozooooozooozoo zooo

ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο

m m m m m m m

7> C-. ^ C — ^ o o co co oo co oo o oo

en — »-oo oo r — ⁱ -oo oo --J 400n oo cJ) C7> -c ^ cT> io oo co no r> cn oo o) oo-*-J-^ J oo tn σ¾ r -jo — * ■ o σ> r — ^ — ^ h COO 71-^ O r O) U ron o> — ^ to o> rr oo c cn o5 05 — »· OO CO""--l O CD O rS3 h O CO OO rS3 J1 ** J CO — ^ oc-^-^ CO o σ¾ r — ^ σ ι C OO A 400ji ho --j ri c7><3> — * ^ ^ ^ — ^ chn ji cn oo ooo

IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII co • ^ cc od on oo cor 400-"i oo? Nc ri ho — ^ o to oc cji oo — ^ ι ο r ^ o cn-i co ro o> oo ji ro-^ c — *-c oo ho> oo — *--p *. ro ι σ> rc «« -j oo ro --- 1 ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο ooooooooooooooooooooo ooooooooo, oooooocc co cccccccc co crhr oo-^ I co --- i ^ ho c oo oo c ^ o ^ cc oi oo-^ j cri croo — ^ ho — ^ O oo o oo co co--jhn oo-«J cr" -J-»J o σ ο ο i CT¾ oo>« -J co cri cr

ο ο ο ο ο ζ ο ο 2: ο ο ο ζ: ο ο ζ ο ο 399 ο ζ ο ο ο ο ο ζ

8 39

o o z o o z o z o z o ^ o ^ o

 CO 3 C7 CD CD OD> C7 ϋ CD 3> CD CD> CD C5 0D> h 1 ^ ro h h 1

 > GO> CO> CO>> O> CO 「「 「「 「「 「coo cj oco oo mmmmmm ΓΠ" D "D" U ~ σ "3 -ommm rn mmmmcccc co co ccc ro rrrrrrrrrrrrh _ *-oooooo to to ooo co o oo cx> oo cx> oo oo one> one _k rhrrrrr one one one one one one one one one one one one one one one one one one one oo nc cji r oi o

-&. OO 0O — * ■ — * r <o

oo _ oo <o ro --- J

 1 —> ■) — ^ ttllllllttllttltlllll ltllllll co o co o co o co ji n --- io> p¾ ^ J O¾ o ^ ^ ^ I ^ ^ O ^ JSO OO one o one oo ^ ~ * οο <ο "^ --- ι οο --- 1 ^) co co oo ο --- ihj ^ j ^. ^. — *-non 3 0¾ o co rh ^ r ^ ^ oo ^ ri c ^ o) ^ o ^ oo oo ^ oo cri o rs3 o> corca ^ o ^ rco oo-^ ^ j ^ h — ». o σ¾"-I --J-"-1 — ^-^ oo-» «j-^ oo oc ^ 05 n ι rsa oo in oo oo oo or -j oo o¾ o

IIIIIIII 1 IIIIIIIIIIIIIIII f IIIIIIIII Iji n ji cjn ji cri cji cji n ji crt cji cji ri n ji 4 ^ ri ^ ji ji ji ji n cri ri ri n ji ji cn ri ri ai oi ji o¾ <o oo -J o ^ J — *--^. Nro oo ji o¾ ^ ji — iro ji o oo co ^ J h cji ji n oo o cAS. — ^ Ichi c ^ * -jo> <to o ai rs3 0i h * -j an oo o ro oo oo ^ j co 4 ^ <o ~ »" ai ^ jcc --j «ι on 4 ^ co roo oo cj) ^ n-^ — ^ --JOT> i an oooooh oo o> ^ j — »-Oo oo ocn ^ 4 Ji oo cn ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo oooooooo

0O h

0O

ο ο ο ζ ο ζ ο ζ σ ζ ο ο ζ ο ζ ο

謹 4020 >>>>>>>>>>>>>>>>>>>>>>>

 o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

Z O ^ O O Z O Z Z Z Z O O O O ^ O

 C3 C73 C3D D N m C7 C¾ 03> O CD>-m i- i— r— i— i— mmmmmmmm ^ ^ ^ ^ ^ ^ ^? O ^ 3? O? D r- | — r— I — I— i— i— i— i— co co c>>>> ^ —i ~ I ~ I ~ I ~ I — 1 — l OOG ^ CC CZ CC CZ CCC "Ό" O ccccccccccccccccccccc ccccccccc

— ^ C 3 4 ^ c ^ 4 ^-^ 4 ^ n cn o> oo ^ j ^ ι co oo oo 1 oo σ> n σ¾

 σ> O) o σ ι oo ^ co 1 co 45 *. ΐ *. ""-«ι -p *. — ^ 1 oo ^ ι o¾ oo o σ¾ — ^ — ^ ^ ι 3 cji r oo oo o ^ -J cn oo — ^ co oo oo ""--1 — ^ oo — ^ oo r o¾ oo> — ^ oo o oo c cn ri oi co oo one oo o oo co one oon A Oo oo a¾ o one co n one cj ^ ch cn ο · -ο ςο σ · ^ οο one o

 Three

h ο ο ο ο One Jifc One ο ο

 ο r ο 4 ^ co οο σ 1 o ο θ) ο ι one <oo> o¾ o o¾ oo co ai oo oo σ> οο σ> οο · ^ one "· ■> ^> ^> t ^ j ^ j ^ ^ ^> nnn oi nn ai A Cji oi n ui nn σ¾ απ σ> <¾ο ο ο ο — *-c oo ho-^ "-i o¾ o co n one o crt ho n one h cn c οο ο σ ai r one rc DOO> an <c oo o¾ one ο οο οο ο οο · *! * · ooooooooooooooooooooo ooooooooooooooooooooooooooooooooooooooooooooooo oooooooo oo occ on one 0 * -J c oo o oo co one ho o cn co oo one ≥ *> o

zoooozooooooozoozzozo ooozoooooooozoo

0 39 "9200 ι 90fr ΖΖ- m '9- 299 ε- 0 0 Odd 0 92 117 ■ V

0 n 00 913 '9S-B ss to LZZ ι- 0 0 Odd 00

0 B S 11 00 ι Z9L 'εε- 109-f- LLP l- on 0 Odd 90 I / IIOIV

0 οε n 00 ι 9εζ., Εε- 982 • s-8C8 τ-on 0 O d V. £ ΖΙΡ 隨 V

0 6332 00 ι 06 B SS- 800 ε ^ 9 'Ζ- O 0 Odd αο zV

N O 6 ZZ 00 ι ι 6 ε-To m ■ ε-OH 0 Odd Ν \ m ■ V

0 00 ι 999 Κ- m • s-6ε s- 6ε ι 0 dSV 0 cm

0 69 ζ 00 ι ILZ SS- • s-m 6ε ι 0 dSV 0 6Ufr

0 zz 00 ι 099 "9S-LOZ • l-m • 9-6 I 0 dSV ZQO 8Llfr ■ V

0 οε 'εε 00 ι 903 "9-696 l-G 0 dSV IQO LllV WOIV

0 66 οε 00 ι 9009ε- 8 z- 098S-6ε i 0 dSV 00 911VV

0 τι 00 ι ζζί '9ε— • ε-ZIP • 9-0 dSV ao 9Ufr ■ V

0 η η 00 ι S89 '9ε- 689 6οεS-D dSV νο

N τγττ 00 ι 063 LZ- "9-" 9- 0 dSV Ν woiv

0 οι ζ 00 ■ ι L6Z 6ε- ZZL "9- 0 ΊΥΛ 0 zn 1N01V

0 C9 13 00 ι 969 "8ε-B 69" 9- OLO • 9-891 0 1VA 0 ■ V

0 68 '91 00 ι 386 Total 996 • 9-ε B 8 'G 891 0 1VA 390 OLLfrV

0 O 0.61 00 ι m • 6-9 O 0 ■ 9-8SI 0 1VA 190 60 ■ V

0 £ 8 ΟΖ 00 ι m '6ε- m O-21 ■ S- 8SL 0 "IVA ao 80 It- ■ V

0 C6 ΟΖ 00 Ί 161 '6ε-z% • 9-■ 9-8 £ l 0 1VA νο Rising WOIV

N 1 ΌΖ 00 ι I-099 • 9-ε L- 8SI 0 "IVA ΝV

0 ΖΖ 00 ι 968 '8S— 09 O L- 983' 6-O ει 0 3, l 0 90 If WOIV

0 10 00 ι W6 6ε- 811 L- 986 '8-n ει 0 311 0 歸 V

0 ^ 811 00 • ι 086 '8ε- m-989 ■ 6-LZl 0 3, l ιαο WOIV

0 89 13 00 • ι 891 '6S- m' 9- LZL 01- ει 0 311 ■ WOIV

0 03 τι 00 • ι 838 Ofr- n \ • 9-LLZ ZI- O ει 0 311 ΖΘΟ ■ Drawing

0 ε w 00 • ι U9O17-B 69 9- 396 • 01-B ει 0 311 90 00 WOIV

0 00 ι UO Ifr- 098 ■ 9-• 6 -B ει 0 311 νο 66017 WOIV

N 9911 00 ι 160 • 8-• 0 G ^ ει 0 311 WO Request WOIV

0 00 ι-OS B • 8-no '6-9ε ι 0 Π ょ, 0 WOIV

0 π η 00 ι 091-096 '8-680 01- 9ε L 0 0, 0 960fr 隨

0 B 9 "92 00 • ι 390 Gfr- ει- 0 • 6-0 Π31 ZQO 960fr WOIV

0 frO 63 00 ι ε sfr- 636 ZZL-9ε ι 0 Π3Ί ιαο 60fr

0 0 2 2 00 00 ι LZ5-988 ζι- • 0 to 9ε ι 0 Π3Ί 00 860fr

0 99 η 00 ι 89 'ichi u-8 8 8 • 6-9ει 0 Π3Ί WOIV

0 6B η 00 ι ωι ζ-6ZZ • οι- 898 • 01— 0 fl Ί νο 隱 WOIV C00 / .00Zai / X3d 6 8 £ 0 / 800i ΟΛ \ 0 00 I 228 • εε- Ί 016 Zi- 0 person, 9 0 z IN01V

0 16 ZZ 00 ■ I zz- 388 Z 9εε • ει- 0 people, 9 VO i WOIV

N 96 zz 00 l 9fr l εοβ m 0, 9 N o V

0 98 oz 00 L 889 zz- ηζ • 0 ει- 0 people 9 0 WOIV

0 ΪΖ ZZ 00 l 8 B 9 ΛΖ- 189 • 0 ο ζ • ει- 0 people, 9 0 隱

0 6L ZZ 00 I 909 • οε- Ό- ζι- 9fr l 0 people, 9 VO WOIV

N 9Z 00 ■ I ZL9 63- ZLl ■ 0 666 0 people, 9 N WOIV

0 89 Z 00 l B 01 82- 08ε Ό 869εε m 0 «Η1 0 9 117 WOIV

0 frS 83 00 I B 6ε "82- εε Ό WS ΊΙ- m 0 dHl 0 WOIV

0 IZ • οε 00 l B 19 9Z- ε 9 ^ 9 οι- 0 dHl ZOO 1 / IIOiV

0 ZO ZZ 00 I 088-990 • ε u-m 0 dHl 190 WOIV

0 S8 6Z 00 I S LZ- 89 I m '-0 dHl ao WOIV

0 LI 6Z 00 I B 6ε LZ- 891 Λ 399 is-0 VO WOIV

N 09 6Z 00 l 909 LZ- 389 0 881 • 01- 0 N 6 fr WOIV

0 S8 OS 00 ■ I 898-9ZL • 0-9 B2 ■ 01-zn 0 V1V 0 8 fr WOIV

0 96 U 00 i 918 9Z- m • 0- 999 ■ 6-zn 0 v, v 0 LH) f 隱

0 UV LZ 00 • I Ll l LZ- εε ^ • 0 ZLZ B-zn 0 V1V 90 9 fr WOIV

0 93 83 00 l 991 LZ- 乙 Ό- • 8-zn 0 v, v VO WOIV

N 91 92 00 2Z- 9 ^ ε Λ- LZZ • 8-zn 0 v, v N ni WOIV

0 00 00 l 069 LZ- • ε- 038 • 8-in 0 0, 0 WOIV

0 29 "93 00 l 819 Z- H9 z- • 8-in 0 Π3Ί 0 WOIV

0 SS 00 L m 'οε- 899 s- 99fr is in 0 Π3Ί 200 WOIV

0 91 • ιε 00 • I 18- 60 ε-0 6 01- zn 0 Π3Ί ιαο WOIV

0 εε 6Z 00 I 08- m-2ZL 01- zn 0 Π3Ί DO WOIV

0 96 00 I 022 ■ οε- m-ZZZ ■ 6-zn 0 Π3Ί ao WOIV

0 89 LZ 00 I 630 οε- m • ε- • 8-zn 0 fl 1 1 VO WOIV

N 08 LZ 00 I LLl • οε-0 0 9 • ε- 336 ■ 9-zn 0 Π, N 9CLfr WOIV

0 99 οε 00 I O OS ιε- 6 ι- ■ 9-0 丄 W 0 WOIV

0 89 LZ 00 I 6 B 8 'οε- 386 ζ- ^ εο 9-in 0 丄 W 0 WOIV

0 11 LZ 00 • I 338 63- 993 Ό- 869 1-0 丄 31111 o WOIV

S 09 00 l SO 63- Λ- z 1-in 0 丄 as WOIV

0 ει 92 00 l 090 • οε- • τ- L9Z Ζ- in 0 丄 W 90 WOIV

0 38 9Z 00 l S61 'οε- 009 ζ- 989' ε- in 0 丄 il ao WOIV

0 9 O LZ 00 l 398 οε-O IS ε- 909-in 0 丄 VO 6Z WOIV

N 8fr 9Z 00 I 6 I ζζ- 698 • ε- 8 0 0 丄 W N WOIV

0 30 9Z 00 l 289 ιε- 086 9- ε-on 0 Odd 0 LZI I / IIOIV C00 / .00Zai / X3d 6 8 £ 0 / 800Z OAV ooooo

o <o <o <o t c o oo oo oo oo oo oo oo oo oo oo 1

^ OOO ^ OQZOZO f ^ ZOOZO ¾ OD 3 CD 3 σ OD C5 C¾ CD J * CO 3

 2! O O O Z O Z O O Z O O Z O O O Z O

o o o o o z o o o o o o o z o o o o o o o z o o o o o o o z o o o o o o 。 G

ooooozooooooozooooooo zooooooozoooooo.

 One one one

"" "" "" "" "" "">>>>>>>> 1. tn ai ji Ji cTi cri jn nn ji ai ri ri ji ji ji ji oi cn oi cn nn ai cn cn cn cn i oi cn cri cn ji a¾ 05 CT¾ a¾ o¾ o> oi oi cn oi cn cn cncc «t ^ cccccccr ho orrh one one one r

r oo o one --- co σ> oo "-to o cg ^ CC ^ CC oo | Ji | Ji oo io jO! ^ ^! ^-" ¹ ? ⁰ ? ^{0 00}

I

I

 Two

Awakening

4199 ATOM 3> 3 »

ooooo

 Z O O O O O Z O O O O O Z O O O O O Z O O O Z O O O O Z O 3 C5 0 Z O O Z

 C5 O0> C5 CO> O OO 3 »3 00 3» 00 3 »N 1 0 C / 5 C 0 0 C C & C C C C C & & & 0 0 C5 C5 C3 C5

 I ~ m m m m rn m m m m m m m m m m m m m r ι ι r o r <h i> iv3 3 1 1 1 1 1 O O O O O O co co to to oo oo oo oo oo-1 1 I 1-1 σ> σ> σ>

I I I I I 4216 I I I I I I I I I I I I I I I I I I I I I I I I I I I I o h one iv3 ~ * o one o o one o o o one o o o o o h one one one r one r

CO CO — J ^ JI — ^ O 00 0> C0 00 — J 03 C ~~ jr-1-~ jo — ¹ c 3 i rss cnc »rn σ> n

^ ho> o -l ^ cn o ji oo cn oo o cn — j ^ nc — ^ cn oc ^ i rsa oo-en-~ j σ>-1-1 — 'on — ^ co h co co o oo -j-ι σ) ∞ ο o-en lon

 I I I I I I I I I I I

1 1 1 1 1 1 1 1 1 1 lllllllllllllllllll 1 1 1 1 OO ^ C — 'OOO — ^l O C0 00 0>-~ J 0¾ 0¾ C3i jn O> ri ^ C r <J —' ― 'OOO — 'OOS Isa tTI l io o oo —' cn oo cji c rva isa j ^ CTJ cn c — 'tsa-1 cn ~-1 o¾ co — ^ oo —' — ¹ ~-ic cji — '

cri cji oo oo rsa oi oo oj hr ji — 'θο i cn cn co o O) <o o> oo ~> j (o ¹ ^ 1 ^ 1 0-1 4 ^

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

 4 ^ J ^ 4 ^ _ ^ _P ^ J ^ 4 ^> (^ ^ ^ ^ ^ CO

— I c c h c c ^ oJ 4 ^ o> ai n cn n (7> (7> n n ~ «i oo c» <o oo o o co co ~~ ι oo ~ »ι σι oj cn cn on oo

>■> I co o ~~ I ~-icj ^ rvj h co cco ai — 'n to <o oi ~~ i ji r oo oo oi r <is3 co cn-1 o co co o co en £> cn <3¾ cn <3> cn — 'O h jik Cn c rsa rj rsj ι one O 4 ^ o rvs one c to o one ¹ 1 ^-1 co oo n ro cn one one co one o> r one cn 1 to oi oi ~ · ι 1 ■ ^ lono-^ ocrc oo-^ jor co cn u ai co r ^ ooooooooooooooooooooo oooooooooooooooo ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο οοο ο ο σ ο ο ο ο ο ο ο ο ο ο

oo cn o io rsa r to (^ ー ー & ^ ^！ ^ o σ¾ oo cn ai oi ~-i oo r

oo cn o io rsa r to

zoozoozooozoozoozozoz

0 28 • 61 00 'I LZZ • ιε- 603 8- W9 O-L91 0 1VA 390 90Sfr I / U01V

0 ZZ • 61 00 I ε • εε- 080 L- • 8- 91 0 1VA 190 隱

0 91 Ζ 00 I-8SS L- m B-B 91 0 1VA ao 隱

0 16 OZ 00 I 'εε-999 2-LOZ • 9-B 91 0 1VA V. εοε ^ 隱

N 88 OZ 00 L 880 ε-99fr 6- L80 N-B 91 0 1VA N W01V

0 9fr OZ 00 1 286 ■ gs-8 8 ε • 8-99 B • 9-. 991 0 Π31 0 ■ ■ V

0 36 Z 00 9178 • gs- 90S • 6-193 L-991 0 n, 0 cm 隱

0 96 Π 00 I 089 LZ- 118 ζ ι- 66 ∎ 8-991 0 n ZQ 66 II1I01V

0 89 Π 00 I 600 6ε- m 900 L- 991 0 n Ί ιαο 86 IIU01V

0 6S ZZ 00 I LZl 8ε- LL2 u- B 66 L- 991 0 Π31 90 6 ΙΝΟ 丄 V

0 2L OZ 00 I LZO LZ- u- L- 991 0 Π31 ao 96 W01V

0 9fr Zl 00 l 690, 9ε- • 01- • 8-991 0 n Ί vo 1N01V

N 19 n 00 ■ I L IL ■ 9ε- 069 '6- LZZ' 6- 991 0 fl, N i WOlV

0 0 9Z 00 ■ I "98-189 • 01- LSL port 991 0 1VA 0 S6 WOIV

0 Ifr 9Z 00 I L6Z "98-988" 6-m ΌΙ-991 0 1VA 0 W01V

0 31 OZ 00 l 8fr9 9S- 992 L- 993 'ει-991 0 1VA 390 16 I / UOIV

0 86 '6 L 00 • I 939 9ε- m L- 186' 0 G S91 0 1VA 190 06 I / UOIV

0 09 £ Z 00 I 210 9ε- 010 "8- 601 Ι Ι- S91 0 1VA ao 68 I / IIOIV

0 \ L ZZ 00 • I 986 '9ε-B 80 • 6-Z69 11-991 0 1VA vo

N 80 ZZ 00 l 898 LZ- 986 6-0 9 ΖΪ-S91 0 1VA N 8 WO 丄 V

0 B ε ZZ 00 ί U9 ■ 6ε- 8 ^ 9 6-G W l 0 S people, 0 98 WOIV

0 82 ZZ 00 L 639, 8ε- m ■ 01- 010 ε m 0 S people, 0 WOlV

N 89 83 00 l 8 L I, 6ε- 993 L [-IS l '91-m 0 S person, ZN WOIV

0 00 "93 00 I 88 6ε- ^ 6 [-6is '91-m 0 S 30 S8 WOIV

0 01 "92 00 I L L9 6ε- 886 n- 081 η- m 0 S person, GO 隱

0 9Z 00 • I ag ■ 6ε- .SS • ει- 60 η- m 0 S people, DO 18 IN01V

0 16 ZZ 00I 899 z \-099 'ει- m 0 SA1 90 08 隨

0 εε n 00 ■ I 698 · 8ε- 881 'Ha-8 O ι n- m 0 S people, VO 6 O I / UOIV

N 99 00 ■ I 890 O IL ■ οι- 268-m 0 S people, N WOIV

0 B 8 00 l 9L \ • 6S- m 01- £ 96 "91- 891 0 311 0 IN01V

0 Sfr "92 00 l 901 017- OL- 313" 91- 0 311 0 9 O I / UOIV

0 88 00 L ζ-• 9-LOZ 81- 0 311 ιαο 9LZ I / IIOIV

0 S8 00 I '-8 8 L- 9 9 L [-0 3ΊΙ 190 HZV 隨

0 9fr 00 L 3 L9 w- L- 996 "91- m 0 311 3D0 εV

0 Z \ ZZ 00 l OH 117- U9 '8- O 91 LI- 0 311 90 ZLZ17 I / IIOIV

0 00 Z 00 l 068 C86 • 6-8 O '91-0 311 VO 1 O WOIV

r> 一 Γ· 一 L08 £ 00 / L00Zm / ∑ d 6M8 £ 0 / 800Z OAV

r> One Γ · One

 £ 7> β5

* -j ■ "-1 '^ I ■ 1 σ> σ>>> o>> r>> σ¾ cn cn cr> cr> ¾ σ>

OOOO U3 (OC (£><O C0 C0 CX> CO 00 00 00 C »00 00 ~~ l I c OJ one ivo o one one o oo to oo oo oo oo-i CT5 0" i O "i CJ r D C0 ^ co co i o i oo j ^ on n rsa c en nc-i ji 4 ^ ^ c <35 <£> — ^l 05 0 r to oo cn tC) --j --j eo oj ^ oc cn rs3 cn-1-~ J oonr ~ j en O-1-1 ^ co c-\ tn σ>-i to -jro -Pk Cn oJ iva c cji-ia> or ao oc (0 (or <^

^. 4 ^ — ¹ ~~ I co-i on co o-ι ο — ^ o co co ~-1 one ^ one rsa co co c oj c -jcc to one o><oo to o5 one 05 " 1 ^ 0) 0 00 i oo A hoh ^ J i oo tn co or OJ j ^ r i c i h ~-1 o i

c tva croo rva — 'isa j ^ ccc ri j ^ ri-^ j en oj oo oo ai ~-1 i oo o to co co c N3 one r> h 3 cc oo cn c as o to n cn c ji ^ ir oo r cn oo co -t ^ o cn -i ^ co-in one one to oi co one

~~ J h> CT) ^ 00 0 Ichi I Cn O> tO OO rs3 J1 C CO Or> OC CO CX5 0 0 rv3 00 CO r> 0-~ J OO O CJ> £ 5 ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooo 0 — 'O OO OO OO tO «S 0-I OO 3 01 ^ ^ ^ rs3 ^ 4 ^ N3 ~ J 00 ^ 4 ^ 0 CO CO O —' O — ^ tss tsa oo — 'Co o ji co — ^ c »o -C ^ oo cn-ic cn oi ^ ooo oo n ^ n-1 one rsa ^. a¾ o>« 0 ^ -ti. «oo — ^ oo yi c cn cn ~~ ι ο one ao cn one n co-^ one one 0 one Oi O one zooozozoooozooooozoso oozo

CD

c: C5

c:

• co r oo c cn -tfc — ~ cn oo co O ~ ^L o ~ ^L σ oo ~ ^L — * · c σ> ~ »■ σ oi oo oo O cri oo nio ro o --JO o o¾ ro co cnc — ^ ^ 1 c

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

n oo o o cn r — 'Oo co c CTi CO — »-0" «-ι oo <o¾ o co o" ^ c n o c c

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I o t \ 3 ts3 0 0 <o o to * -j --- 1 sσ

* »» J cri r ^s oo O "^ J O¾ o --J c oo ho oi *"j-"j o¾ oo co o> ~ * · σ> ^k n --- r oo ι co or ~ *" -»J co n o¾ i ji oo oo oh oo o¾ 0 ^. 0 h ^. O ts3 0o c oo — ^ ^ oo on-^ jh ^ ι σ¾ — *-f \ 3 C o oo -t ^-" chc oi o oo co o-«joc * -j ro ooooooooooooooooooooo ooooooooooooooooooooooooooooooooooooooooooo oooooon o¾ co c o¾ 05 J rhrc AO Oi — * ^ ο οο ~ ^ οο σ5 · Ρ ^ ο o 0¾

z o o z o z o z o z o o o o

4343 ATOM 5 3 »--3>->-3>3>3>3>3>3>3>-3>->->>>> 3» ooooooooooooooooooooo ooooooooooooooo

σ m ϋichi σ σσ 5 σσ> h i m σ σσ · m m ϋ c¾ θ3 3

 r one r ro — »·

 G <-G <-O -O ■ G <-O <-O -O-<"" "" "" "" "m

一cji 1 o

Cji

I I I I I I I I I I I I I I I I I I I I I I I I I I One I I I I I I I

<o o c3> o tD C i oo oo ^ co o> ho o¾ oo-^ — ^ oo n n o ji <o-o — »■ ι

IIIIIIIIIIIIIIIIIII 1 f IIIIIIIIII! III I I c c «-j-^ j * -j ^ 0" -jocccc cji hoi rsj o -P> .cri <o oo o -p¾.o> o o¾ oo o rs3 n ri <3¾ co h oo c -i ^-«jto — *-o> oo-* J Oo ^ CT o ι οο ο ^ ο ο οο — ^ o> ooh ^ n ji <oc cji oo one co ji cn ocr σ nio o¾ nooor ^ p oo -j ^ oo n ι oo 1 o σ¾ ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooi cji r — »-co cn ji h — ^ or

 o h oi h r ot h c ro i — *-O c o n i o> n ji oo oo o) C oo

 h n oo c oo c co O h o o> "P one o ho cri c ro co o oo o D Oon to o> 0" * j n co one o one

ozoozozoooozoooozoozo oooozoooooooozo

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

o σ σσ> ■ rn rn o 3 o crs> o 3 c¾ oo> 3 r 3

 C¾ C5 C3 £ 73 C5 C¾ C¾ O C> <<<<<<<>> "0" 0 "0 to 0 rn m m m m m m>>>>>>> o o c c G o c c iO ^ σ; σ; ϋ

o> o CCCCC CI C CZ C CZ C c CCCC "O -D TS ^ D ^ D ^ OOOOOO oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo cxa oo oo oo oo oo oo oo rhr ro ho rso r an o o¾ oh-■ j

o> o

ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooro ho hrrhhcrrro ro rhcccc co cccc <T oi --J Ji ai o¾ o> n oj <"-jo oo oo *" »JO o ο <ο ¾ · ro oo ooooo σ¾ oo oo o

ozooooooozoooooozoooo ozoooo

ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο

 O O O Z O O O O O Z O O O O Si O O O O O Z O O O O O O Z O

00

 0 0 Z 0 0 0 0 0 0 0 Z 0 0 0 2 0 0 Z 0 0 0 0 0 Z 0 0 0 0 0 0 0

£ 75 οσ> σ ϋ c¾ 5> rn m ϋ σσ 3 σ σ ο σσ> σ —

 -<o c o oo c c o o

CO O O <CO to CO CO CO CO <o co <o <o <o <o <<o <CO c t to CO O c <<C CO <CO CO

I I

 4 ^

"" -jo rs r co oo co ^ a¾ ocono a¾ co ai --jo oo ai hn oo oo "-1 on co · = ^ i ^ oi co rsa oc ¹ ) c cr>j" i ho oo> ι ^ ι αι σϊ

oo o o ho o σ oo ro — * oo O O h h D O ^ oo σ¾ — ^ o oo ro oo o o o o oo c ji r cn ai o¾ cr> o co — o r to σ

oo oo ho o σ oo ro — * oo OO hh DO ^ oo σ¾ — ^ o oo ro oo oooo oo c ji r cn ai o¾ cr> o co — or to σ

 o oo — ^ co ro o oo o o oo o cn 1 σ σ> — *

 I I I

 p OO

to o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o .o o o o o o o o o o o o o o o o o o o co c oo o *-j "»-j oo Ji c co co i ho o o¾ co n co -p*. <D O cn ai — »■ --- 1 Oi oo co o co c cji — * · o co

to ooooooooooooooooooooo ooooooooooooooooooooo oooooooooo .ooooooooooooooooooo co c oo o * -j "» -j oo Ji c co i ho o o o¾ co n co -p *. <DO cn ai — »■ --- 1 Oi oo

o o o z o o o o o o o z o o o z o o z o o o o o z o o o o o o o z o o o

ATOM 4487 0 00 'I 290 S2- 06ε εεε ι ιοζ 0 y people zo 89Sfr 1 / ilOlV

0 '6ε 00' t 9Z9 '93-6980 \ oz 0 no 隱

0 S'9S 00, I ZOO 0 10Z 0 999fr IftlOlV

0 Π 8G 00 'I 008 τζ- OLL 836 10Z 0 dAl 130 999fr W01V

0 99 9ε 00 I 960 ZZ- m z 190 Ό 103 0 dAl ιαο W01V

0 s ε 00 L 9S9 τι- z 'ο-103 0 dAl 90V

0 39 Π 00 L 8 11-B 98I Iει-102 0 yAi 90 399frV

0 00 L 90ε zz- i 09 Otsu-103 0 y I99fr WOIV

N 00 I m zz- z 009 ε- 102 0 y

0 ZL '9ε 00 l 829 Π-6 B i ε 68 B 002 0 kid 0 WOIV

0 ss' ε 00 l m zz- s ε 98fr 002 0 people, 9 0 WOIV

0 30 'βε 00 l ZZQ 11- "9 9- 002 0 people, 9 V. WOIV

N s 00 L iz-6½ "9 m fr- 003 0 people, 9 N 9 WOIV

0 686ε 00 l LZZ τι- ILZ 9 ui ε- 661 0 SIH 0

0 00 • I 80 ZZ-10Z 9 21S 8- 661 0 SIH 0 WOIV

N 00 • I 90 '6 卜 ZOL' 6 931 Ό 661 0 SIH 33N WOIV

0 99 Sfr 00 • I 083 "81-299 '8 ΖΖΖ Ό 661 0 SIH L30 Sfr WOIV

N B S '9fr 00 I 98 '81 — 0697. 691 Ό-661 0 SIH LON 隱

0 90'9fr 00I 661 OZ- Z 6 3S9 Ό- 661 0 SIH 200 o 隱

0 00 l 080 OZ-6 L 61 Otsuji 661 0 SIH 90 WOIV

0 00 l 966 QZ- 696 '9 ZLZ l- 661 0 SIH ao WOIV

0 zo 00 l 236 OZ- 286 '9 306 Ζ- 661 0 SIH V. WOIV

N 00 l W9'6l- 119 '9 ε- 661 0 SIH N WOIV

0 9 00 • I '61-81 O 633 '9- 861 0 mo 0 WOIV

0 S0'9fr 00 l 190 '61-096 '9 3917 861 0 ma 0V

0 1639 00 l οε ι- e 989 861 0 ni9 330 隱

0 0339 00 L C9i η-961 '8 LLS Ζ-861 0 ma L30 zz ^ WOIV

0 88 X9 00 l 662 n- m 8 ΖΖ2 ε- 861 0 mo ao IIU01V

0 S S 00 l 6L3 91- L9Z L 309-861 0 n, 9 90 WOIV

0 lS'8fr 00 l 9C9 91- ZQZ L ε-861 0 fl, 9 90V

0 99'9fr 00 l m L-m '9 861 0 niD VO 839fr WOIV

N 98 00 919 a- '9 m-861 0 niD N LZ ^ WOIV

0 00 I 898 '61 -ε v εB s' 9-B 61 0 NSV 0 939fr WOIV

0 ZL 00Im 8i- 898-61 0 NSV 0 WOIV

N 61 8ε 00 l 8 '61 — 9S9 Z m 乙-61 61 0 NSV ZQH 隱

0 ZL 0 00I ZZ OZ- 039 ε Z08 Z- 0 NSV iao WOIV £ 00 / Z.00Zai / X3d 6 8C0 / 800Z OAV 2 ATOM 4594 CD2 LE 1.004.U08 o

one

o

 I

r

crt

_ t

one

0 0 0 3E OZOZOOZOOZOO

ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο

ooooooooooooooooooooo o oo σ> --j-

 t I i I I I I I I I I I I I I I I I I I I I t I I I I I I I 1 I I I I I co o> t eleven - -J Oi o ri 4 ^ C7i c oo one οο οΐ ΓΝ3 θΐ οι one <oo r> o¾ ** j c c oo <o a¾ o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o one

1>"^ 1 1 0 2T OOOZOZOOOOZOOOOZOOZOO

0 S8 '6fr 00 I in xc- 6 • L 9S9 • 8 LIZ 0 s person, VO 9 ■ V

N L 00 I 396 '9 909 • 8 L iZ 0 s, N 99917 ■ V

0 99 6ε 00 I 08S • εε- 380 9 6 • 6 nz 0 丄 0 潘 W01V

0 69 6ε 00 l ε- g 090 • 6 913 0 ¾JH 丄 0 隱

0 S 00 III 8ε- g 131 • 8 913 0 丄 2DD z W01V

0 O 8 ε 00 I \ \ z 9ε- 910 s S9 O • 9 912 0 ^ 丄 L90 隱 J01V

0 00 I 6ZL '9S- LU' 9 226 L 912 0 丄 aoV

0 09 00 ■ I z "98-m" 9 8 ■ 6 91Z 0 yH 丄 VO 699 ^ W01V

N 09 ■ ιε 00 l 630 "9G- ε 993 ■ 6 913 0 yH 丄 N 899fr WIOIV

0 93 00 l 8S 9ε- m • ε m U 913 0 people ”19 0 W01V

0 83 00 l LL • 9S- 003 ■ ε • 01 913 0 people, 9 0 999fr 隱

0 93 00 ■ I L99 • 9S- 669 ι 2LZ 01 913 0 people, 9 VO 999fr 隱

N 36 ΛΖ 00 • I 080 B ε- 893 L 996 • 8 913 0 people, 9 N WOIV

0 29 OZ 00 I zoz6ε- 696 l ZZZ6 nz 0 3Hd 0 隱

0 ZZ 00 I m 8ε- l • 8 nz 0 3Hd 0 隱

0 fr9 LZ 00 I Ifr- 019 Ό S 8 Z z 0 3Hd ZO 隱 隱

0 O 9 LZ 00 I no • Ofr- 301 • 0 210 Z nz 0 3Hd 330 隱

0 L I 92 00 I 268 • Ifr- 668 • l 88 B ε nz 0 3Hd 130 em W01V

0 Π LZ 00 I m • 6S- 069 • 0 0 nz 0 ° Hd ZQO 2m ■ V

0 16 9Z 00 I L l lIfr- 088 l 9 ^ 8 nz 0yo Hd ιαο L

0 8 O 9Z 00 I L 6ε- Ϊ 666 nz 0 H Hd 90

0 ZZ n 00 I 986 8ε-znI 3819 nz 0 3Hd 90 9m

0 Z l ZZ 00 I m 8ε-238 • 0 981 • L nz 0 3Hd VO

N LZ ZZ 00 I m B ε- m • 0-899 • 9 nz 0 3Hd N zm 隱

0 89 ZZ 00 • I m '8ε- 168 l- 009 • L z iz 0 311 0 zm 隱

0 ^ 6 ZZ 00 l Z.99 O ε- ½ε • l- 8 • 9 ziz 0 311 0 im 隱

0 LZ 61 00 l 9ε- 19 B 8- 889 Z ziz 0 311 Lao om W01V

0 8fr ZZ 00I 291 "99-9S9 8- 9U 0 311 190 6S9 W01V

0 89 ΛΖ 00I m8S- z- OIL ziz 0 311 390 8S9 W01V

0 εε Zl 00 I IZO ε- zn z- 9 £ L nz 0 311 90 S9fr W01V

0 6 O ZZ 00 I 9ε- 8 O l τ-281 • 9 ziz 0 311 VO W01V

N IL 00 I m ι- • 9 z \ z 0 311 N 隱

0 n ■ οε 00 ■ I ε- 092 z- • 8 z iz 0 S, 0 ΙΛΙ0 丄 V

0 68 93 00 l 899 IS9 l- 998L ziz 0 S Ί 0 IN01V

N \ L ZZ 00 l 8 z- 90S 9 l \ l 0 S person Ί ZN ZZ9V W01V

0 89 OZ 00 l 96ε "83- 319 i- 961 L l \ l 0 S person Ί 30 隱 W01V

L08 £ 00 / LOOim / 13d 6 8 £ 0 / 800Z OAV 6QL

0 8 οε 00 ι 6 LZ- 868 • L- n Q mo 90 W01V

0 SI ιε 00 ι 9U • Ofr- '9ε- 136 • 9-na mo VO WOIV

N 6P "63 00 ι L9L • 8S- 386 9ε-808 • 9-n a niD N 00 W01V

0 6 82 00 ι 189 8ε- L09 9ε-189 ει a VA 0 669fr

0 39 LZ 00 ι 001 8C- 988 '98-99S-ει a VA 0 869 ^ IN01V

0 S 9Ζ 00 ι ζζζ ε- LLZ '9S- 963 9- 91 a 1VA 390 O 69fr I / IIOIV

0 οε 00 ι O 61 · 9ε- 108 ε- 930 • 9-ει a i L90 969frV

0 91 9Ζ 00 ι L38 98- 6109ε- 903 "9- ει a i 90 969fr WO 丄 V

0 69 LZ 00 ι 9 9ε- Ζ9Ζ O ε- 669 s- ει a 1VA VO) f ΙΛΙΟ 丄 V

N PL LZ 00 ■ ι ιοε ■ 9ε- 9 8ε- m-ει a ΊΥΛ N W01V

0 01 ΖΖ 00 • ι • gs- Z9L'6Z- 999 • 9-ζι a 311 0 z W01V

0 03 LZ 00 • ι • SS-εB s 6ε- "9- ζι a 311 0 ■ 隱

0 OP 00 • ι m "98-6-z- ζι a 311 ιαο 069fr 隱

0 68 ■ ιε 00 ■ ι 299 98- · ε LOO V- ζι a 311 IDO 689fr 隱

0 60 6Ζ 00 ι 929 O ε- 18 O-8 S-31 a 311 390 889fr 隱

0 88 LZ 00 ■ ι in 896 ·--ζι a 311 go L WO 丄 V

0 PL LZ 00 ■ ι 08ε 9ε- 999 Ό m-ζι a 311 VO 隱

N 83 "63 00 ι 196 εε- 198 Ό-Ζϊ a 311 N 989fr IN01V

0 96 • εε 00 • ι εε9 • ιε- m i ^-066 ε-11 a S people, VO 爾 W01V

N ζζ 00 ι 'ιε- 010-1 ^ 96 Ζ- u a S people, N IN01V

0 S • εε 00 ι ss Έε-6S6 "6S- ^ 69 Ζ- a S people, 0 zm 隱

0 90 ζζ 00 ι 890 S8- 8 0 G 81 B • ε- a S people Ί 0 隱 W01V

N 00 • ι 881 'οε- 680'-8lfr ■ S- a S people, ZN W01V

0 90 00 ■ ι ■ οε- 0 9C- 098 ■ g- η a S people, 30 69fr W01V

0 LZ 00 ι 6S O ■ οε- LOfr O ε- 69-11 a S person, ao 89fr W01V

0 εε 6ε 00 • ι ζζι ■ ιε- 618 8S- • s-u a S people Ί 90 LL ^ W01V

0 B 6 9ε 00 • ι 80 B, οε- Sfr8 '6S- 380-LL a S Ί 90 9 B 9fr WOiV

 LIZ 0 S person 乙 S second 9fr y

0 LG 39 00 i 89ε εε- 869 8 m '9 LIZ 0 S person, 1X0 V

0 6 39 00 ι 08ε ιε- 6 L • L LIZ 0 S, 0 隨

0 L9 00 ι 069 ζζ- S '8 [LZ L LIZ 0 S people, 0 zm 隨

N 9 O 9 00 ι O 69 • ss- 8 9 9 699 "3L LIZ 0 S Ί ZN i WOIV

0 S9 00 L £ 83 9ε- 8 O 0 8 6 ^ 6 • 11 LIZ 0 S Ί 30 o O WOIV

0 98 2S 00 ι 109 9ε- LLP, 8 0 ^ 9 01 LIZ 0 SAT ao 699 ^ WOIV

0 18 39 00 ι 960 ε- 389 '8 0C8 ■ 01 LIZ 0 S people, 90 隱

0 'L9 00 ι O 8S' εε- 096 8 909 ∎6 LIZ 0 S, 90 匪 V C00 / .00Zai / X3d 6 8 £ 0 / 800Z OAV

 4 ^ ≥ »_ ^ ^

 — ^ O o o o o o o o o o z o o z o z o o o o z o o z o o o o o z o o o o o z o o o o o o οο> σ ATOM m m σ c¾ σσ> ■ r i m σ c¾ σσ ■ c¾ σσ 3 rn m σ o — ^ — ^ ho h — ^ One

 "

 -D -D "D o o a o o o

TO ATMO 「「 「「 「「

O O O

 籠

 麵

"^ ??? ^ f ^ ^! ?? ^! ?? ^ / ⁰ ^ ^? ^ O ^ o? ^? ^ ³ ^ ¹ ^ ^£ ?? ^> One ^? One o O

 I I I I I I I I I I I ATOM I I I I I I I I I I I I I I I I I I I I f I I I I en I σ¾ cn σ --- n o¾-»j co <<o> n« ^ c h one h r h o one ^ p ^ cn »» -j oo-»j o>

A --j <o o> oo oo *-jOne ho cn

A --j <o o> oo oo * -j

IIIIIIIIIIIIIIIIIIIII I f IIIIII 1 1 IIIII ji cn rcoo One o one one A ro one o one one O h one oo oooooocoo O ¾ 3 h o¾ oro one — ¹ "^ 1 01-^ 0 0¾ ー 0> 01 0 00 00 co O "*" — * "h * -jo cj¾ one c oo ^ ^ ^ cc ^ on oo ooh oo i co c-^ j ^ — ^ σ> — ^ c to o> c oo σ¾ one σ¾ · ρ ^ ^ ^ o to j ^ h --j <oo ^> * -j oo o <hhc oo co ι — * co as to 1 io cr ro ri ** j -j <o o¾ ooooooooooooooooooooo ooooooooooooooooooooooooooooooooooooooooooooooo oooooooo

0 2! O Z Z O Z O Z O Z ATOM O O Z O O O

籠

ATOM

 ^ 4 ^ · A A f ^ _ ^ 4 ^ 4 ^ 4 ^

 --- 1-^ j-^ j 1-ι σ) σ> σ> σ) σ> σ> σ> σ> σ 4 ^ CO oo ζ ζ ο ο ζ ο ο ζ ζ σ ο ο ζ ο ζ ο mm σ σ σο> · Ν Γπ σ θ ϋσ>>-σ σ σσ 5 ah one one ho ho — ^ r one

 --<-"" "" "" ~ ~ ~ ~ ~ ~ ~ M rn rn m m rn rn m

O O -O <O -C <-O -O <-O -G <-O rsD ho h h isj r h 1 1 1 1 1 1 1 o o o o o o o co co o co c co

I one co oo oo ai c

 0> 1 \ 3 00 0 01 0¾-^ <0 00 ー;; 0 0 0 | £> 00 | £> 90 90; 3 90 --1 0¾ 01 | ^ 1; ~ *; ~ »" 1 0 4 ^ 01 01

** j-^ j r — '■ c ro — ^ CTi C c ι ο oi n ≪ »J O c o o"-i oo o¾-»j o¾ ai

 I I I I I I 1 I I I I I I 1 I I I I I I I I I I 1 I I I I I I I I I I Iji ji cn c n ji m an A Oi A A ^ A 4 ^ <t ^> r ^ _P ^

0 ^ 3 0 ^ 0 ー ー 0 0 ¾0 0 01 0> 0¾;-1; 3¾; »"-1; 3¾ 01 01 ^> 0> ^ ^ 01 01 01 01 0

• ^^ i ji o o ro — '■ O h o o — ^ r ^-n ι σ¾ 4 ^ αΐ ο · ^ ο ο ~ «· 一一 一 oo o oo ONE O OO-» J

^ j <^ jco ^ j ji ui n 4 ^ oc oo — * ro ^ ι co ncnio oo o co o-^ oo c 4 ^ — ·-conoocco o¾ rN3 ho i ^ co oo ji ji h oo o oo co oo ^. r co co o an · "-1 ro n-^ J σ¾ — ^ ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo oooooooo ri cocj ^ A nnn fva fND j ^ pi jsD jvD pi jDo jo one 3 CC one one rj ^ cc o o¾ _ ^ <r oo cn one c ^ j ^ i ^ jrrrr one j ^ oo o> o one οο <οο σ¾ one ji o «^ co oi co o>

 4 ^ "-One o¾ c o5 One oo n o o r One r h c o n oo o

o z o z o o o o z o o z o o o o o z o o o o ATMoO o z o o o o o o o z o o o

ATOM ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο σ

 O O Z O O ^ O Z O Z O Z Z O m σ DO 3 σ a?> ·> Σ o CD> · N m c3 c¾ co>

 4806 h one ro one

ssssss "" "" "" "c¾ c¾ c¾" "" "" "" "" "" IE mmmmmm 4805 mmmmmmmmi ~ ι ~ ι ~~ ι ~ ΓΠ ΓΠ ΓΠ ΓΠ ΓΠ ΓΠ ΓΠ ΓΠ -<-<-<-<-<--<-<

I I I I

ooo — ¹ ro rc on o -Ρ> · oo ro 4800 σ¾ en <o »■ i ro c —-^ or ro c — * ho co oo n-^. — ^ o ^ oooco

--- l oo c oo co oi ^ oi one σ¾ οπ co one o> ^ o> c-«jn one αι σ> σ> ^ one c --j ai cn oo oi o> CT> crh one oo oj ^ on a> c ~ »" Oo o oi oo oo one co one * -jc --j ^ ho <o

I I I I I I I I I I 4799

c c r c co rsj r ro ho ho

oo <one o co o <oi

οο 4 ^ <ο ο σ οο Ν3 — »-cji cri oo oo o oo o> o ji h-ι D 1 co o ro o-^ ι -J — ^ σ¾ — * σ> σ¾ oo -p ^ o σ¾ --- 1 — * ■ σ¾ σ> "-1 — ^ ο-^."-ih to ichi cri cn »ι oo« -J 4 ^. co en ""--ionr --jo- P ^ o¾ ^ o ri O O¾-* J <— »-^ o — * · — ^ c oo ^ — *-o¾ co oo an co o¾ I 4 ^ co ro ro-iro ^ -JOO

IIIIIIIIIIIIIIIIIIIII IIIIIIIIIIII 1 1 I One co o ^ a¾ ri o¾ 4 ^ nn oi 4796 One rsa One o oo oooo One o oo "-j * -j oo to o <One non-"-i o¾ oo o¾ ncoocr <o _ ^ o¾ o> c oi N3 C <o «* JO> or ji o — *" o oo o oo ho oo rsD c ho — ^ σ¾ ο ο οι — * ""-«ι οο — ^ oot oo — ^ c co 3¾ — »· 4 ^ — ^ <ο σϊ σ> σ σ¾ ο σ¾»-^ ^ ooooooooooooooooooooo oooooooooooooooooooooooooooooooo 4793 oooooooooooooooooo oo oo ~ * oi co co co oo o¾ c o¾ c ai oo one or oo o>-»joh oo j ^ Ji o A οο σ>-«-ι or co ^ J OJ c ho oo-^ oo oo ri ai c co ooh A oo cn oo ooh

O C O O O Z O O O O O O O Z O O O 2T O O O O 4788O O O Z O O Z O O 5 O O Z O

4777

I I I I I I I I I I I I I

 ο ο one ο o one c one en en n

o O CO rs3 --- 1 ΓΟ CO oo h ■ ""--1 oo OS σ> CO OO o O CD CO -J cn OO CO CO ro CO h ro CO O h CO oo ho ro CO ISO o¾- -1 oo CJl oo O o σ¾ CO oo cn CD CO σ¾ <y> CO o CO oo σ>-»j OO ho O CO oo ro OO n CO o CO σ> CO ro CO an σ> σ>

1 ί 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 r ro CO CO OO CO CO CO C CO CO CO O CO CO h ro ho ro CO CO CO CO C CO C CO CO CO CO O CO CO CO O oo O oor CJl CO CO ro oo O o O σ>-»j <> cn cn • F ^ ^ CO rr

CD oo oo CJl O CO o ro n oo ro ro CO CO nn Coan CO cn CO o oo CO O o Jl σ¾ o to oo oo o cn CO an o O o oo oo CJl h oo o C oh oo CO o CJl CO cn o σ> oo CO ro cn CO an oo σ> on ^ 1 oo

1 1 1 1 I 1 1 1 1 1 1 1 1 \ 1 1 1 1 1 1 1 (1 1 1 1 1 1 1 1 σ> σ> σ> σ σ> σ σ¾ r> σ¾ σ> σ> cn cn cn ln cn cn cn n cn h ro σ> cn ai CO ro ooo to CO oo oo o ro h ^ Jl cn cn σ¾ ro OO h σ> σ¾ "-1 cn hh cn CO OO CO 1 CO σ> oo o σ> oo CO σ> σ> o CO o CO CO CO ^ oo o cn cn CO ∞ oo oo oo o ro r CJl o CO cn σ> cn CO CO oo CD r CO CO ο O cn o CO ho σ> ooooooo ο ο O oooo O o O o O ooooo O ooooooo O oooooooo ο ο ooooooooooooooooooooo ooo O oon on n ai cn CJl cn n Jl CJl n ai CJl Jl CO CO h CO OO ro ro ro CO h ro o oo ooo j CO CO O CO σ> h CO oo oo CO CO o CO 00 ^ 1

CJl σ n o CO σ> CO oo ro cn oo CO CO o cn Jl oo O CO O oo o o O CO Jl cn o o O o CO oo o o oo o oo CO oo CO cn CO ro on

o o o o z o o o o o

ATOM II MT 48 CE D 27 >2488>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο

o z o o z o o o ^ o o o o o o z: o o o o o ^ o o o z o o o

CD I J ΓΠ σ DO 00 ^> CD 3 Ω CD

 7 488 r one one one r ho

 "

 3 GO CO 00 CO CO G One ― One One One One One ―---

ZX3 TO 77 48 m m m m m m "" "" "" "" 0 0 0

 GO 00 CO 7Ό ^ σ ^ σ ^ ^ ^ ^ ΓΠ ΓΠ ΓΠ ΓΠ ΓΠ ΓΠ ΓΠ Γπ ~ σ "Ό -σ

C C C C C C C C C C C OO OJ OO OJ OJ OJ OJ J CO OO C C C C C C C O C C C C C

o¾ o¾ CT> ai oi oi n 4875n ji ai oi ai co c oo crhrh ho N3 or

oocnn xj oc οο 4872 --- 1 οο οο οο — »■ ο co co — ^ o oo — ^ ro jj co r — ^ a ^ ^. cn oo oo oo r — ^ <ο <ο — ^ <ο" -1 ^ cn en n-«« ^ I σ¾ οο One r One ^ ― One ^ —> ■ ro r --- 1 iconn-«« ^^ ι o cn σ>

 n 1-. h-― ― ― CJ> <ο 1 1 ― ^ _p ^ o 1 c 4 ^ n --JO) 1 oo oo 1 ι 1 I ^ CTI-«-J-* JO OO OO" ^ JOO OO OO <O cji ri o¾ c ^ o> cji oo to ^ ^ an — »-oo o <r <n ri ^ oo cn o co o¾ o> o co co o"-ι οο n o¾ _pk-«j ho oo oo h o¾ "-jocc — ^ oo cch one co co"-i ce one cT r o¾ co to n * -j <o one --jro -t ^ c —>-σ> οο — ^ · — io — ^ o <T5 cr <o ^ — io -t ^ c — ^ r — »-— ^ rsj — ^

 I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

 I <ji cji σ¾ n σ¾ ι oo --- ι οο σ¾ ic oo o oo o oo oo one one one one--J OO DO one oc ^ ^ ^. —>-R -p *. ^ Oo cr> — ^ O rvo r ji i cn-^ ho oo o oo ccn ro — ^ ^ h-^ oo r-^ j — * · ο οο ο-^. 1 Α ΟΟ ζΟ ί Ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο 4ο865 ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο o ο οο οο ο One h ho one o¾ chr one i 4 ^. c rN3 ^ o¾ oo D <oo o> co — ^ — ^ <o

■ ^ σ¾ _ρ »> σ> Γ-» ^ οο ο σ θ Ν3 θο σ5 θο αΊ αΐ Γ <ο ο one o> ~ * "one n 1 <co n o co r

-^ jc * -j oo o-»j" f ^-"j one <one" one oo co c oo oO "^ ^ --- 1 en en — ^l 1 — * ■ — ^ σ> c 1 o co en zozozoozooozoozoo

4847 ο ο ο ο ο ο ο ο ο ο ο ο σ σ σ σ σ ο ο ο ο ο σ σ σ ο ο ο ο ο ο ο ο σ ο ο ο ο

m σ C5 ro 3 »N N o c> co> i im m o a c3 D0 3

One one i one r> one ι «one

"" "" ""; Ye ye ye ye: ye ye;

^ o o

 o ι one o -ι ^ σ> -ι ^ to o one one one one one one o o ai 4 one one

 1 <o o o 1 1 1 1

 1 -t ^ 1 1 1 oo 1 o 1 1 1 1 o

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o 49so o o o o o o o o o o o o o o o • ^

ro o> r "« j-^ j-* j oo -pfc. n oo ** jo> o — ^ "-co co"-icoh — »■ —»-ji co ho no — ^ oo ^- o ji

一 O O

One OO

o O one r r — ¹ h one one ooo

 -J oo i oo ro ^ CO CO cn CJl CO n ro CO o CJl CO ro o o

1 <J> oo o¾ O CO h ςο CO CJl ""--1 o o 1 σ¾ CO o ro oo CO oo CD o σ> CO <o σ¾ cn σ> o o o ro CO σ¾ CO cn

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

Γ ro ro ho o ro h ro ro ro ro ro ro ro ro h ro ro ro ho 3 ho ro ro ro ro ro ho ro h ro ho roO CO oo --- 1 <y> ϋΐ cn ho ro On CJl CJl ΟΊ Ji 1 oo oo CO oo --j Jl n σ> cn-^.

CD 00 CO cn 4 ^ on cn CO CJl ro CO CO CO CD O ho O σ¾ oo o σ CO σ> CO oo O CO t σ¾ O ro cn O oo CO cn oo σ¾ CO o CO oo CO CO CO CO Jl » ■ 1 oo ho CO CO O 00 cn CO oo σ> σ> -j σ σ> CO

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 ^ Jl cn ΟΊ Jl cn cn cn OH σ n n cn cn to oo σ> cn --- 1 <J> ^ 1 o oo CO O ho CO o oo h ro O -J CO O o CO o O oo o oo <j> oo CO O Ol CJl o O o 1 CO O oo CO CO σ¾ σ¾ cn CO oo CO cn ^ r> σ> σ> oo O cn CO CO cn σ o oo CO o oo o cn CO Jl CO oo cn O no OO ooooooooooooooooooo O ooooooo O ooooooooooooooooooooo oooooooooooooo o ooooooor CO h ro ro ro ro ro ro ho ro ro ro ro ro ro ro ro ro ro ro ro ro ro ro h CO ro o> cn ^ oo ^ o oo O ho o¾ σ> cn cn cn "-^ 1 o --- 1 ro CJl CO CO O oo hn ro cn ^ o -J oo CJl O ro ro o <> cn CD cn --- 1 oo ro oroh O σ> O oo CO oo O oo σ> cn CO CO oo CO

o o o o o O o o z o o o o o o o o o o o o o o

M ATO 4919 0E2 GLU D 39

 Z O O O O O O Z O O O O O O O Z O C5 C3 0 0 0 0 Z O O O O O Z O C3 0 Z O O en oo> ο σ ο σο> σ σ σα ■ ci oo>> rvs

 —I ~ I ~ I —I —I —I ~ I ~ I I ~ I ~ I ~ "" "" "! ~ I ~ I ~ I ~ I ~ I ~ I ~ & 0 & C C O CS C5 C5

 ~ <Ee ye 3: m rn m m m m m m rn m m rn m rn m m m m m m rn i ~ ι ~ ι ~ ι ~

O tO eO CO <O CO tO t0 00 00 00 00 00 03 CO OO I 1 -— I-1-1 ~-1-1-) CT> r> r> J> CJl J1 J1 n ^- Ci.o 1 1 4ϋ cr 1 oo 1 ooooo 1 o 1 r 1 1 oo 1 1 orr co cc co rsa o 1

~ j οο σ> οι οι σ> n-1 1 1 1 hon — 'r <o — ¹ CTJ -— J CO tsJ TJ tO Ol C —' OO OO n OJ n 71 0 -t ». N3 00 CT> O n CT> -pi. O ^

 -i o cn c -J n c ^ cn-1 co-i cn j ^ eo one o cn o ~~ J one c one--i on

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

o> oo-1 —- 1 oo-1 oo oo o «o — ~ ^ o to 1-ic cD-^ o> o> 7i m cn c .r ^ no oo-~ i oo oo oo oo0 O-1 — '— ^ Jl -P ^ — J —' CJI OO — '― to oo 1 on -P ^ -ta.-1 o <o — ^ to-I OO hhe> e7> C CO O ^ J1 i \ 3 C a> --J OO — ^ cho -t ^ — ^ -P ^ co o ^ occoo co o-1 oo io -t ^ cr cji ^ -l ^ 3 (£> r ( otjn <otjo σ> -t ^.-\ o -t ^-— ^ co ra-1 r <or oo σ> oo 1 one oo tva oo n to oi-1 1 one co ~ 'oo

I I I I I I I I I I C C C C C C & C Ol C

σ> ji.on θ5 oo-i cn oo -j oo

O JI C O C — ' 1 O O ΟΊ OO t D o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ σ σ ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο r isa r isa ho rva iva rsa iva r rss rsa iva rva 一 一 一 一 r> 一 一 一 一 一 一 一 一 rva r iss Ns rsa r tn cn cn c ^-j cn c tss tvi c cn n — ^ co o cn ^j o 1 oo ' ^ ι ~- 1 oo ~- l oo oo o o 一 r c oo -^ 4^ o r> rs3 n c cn h ^ 0 -^ cn c -- ι οο — ^ ^-J C J O Oi r -J n oj c r Na -t^ n o oo-~ JO 00 CO 01 1 <0 7> CO n CO ~-1

O JI COC — '1 OO ΟΊ OO t D ooooooooooooooooooooo ooooooooooooooo ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ σ σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο r isa ho rva iva rsa iva r rss rsa iva rva 1 1 1 1 r> 1 1 1 1 1 1 1 rva r iss Ns rsa r tn cn cn c ^ -j cn c tss tvi c cn n — ^ co o cn ^ jo 1 oo '^ ι ~-1 oo ~-l oo oo oo rc oo-^ 4 ^ or> rs3 nc cn h ^ 0-^ cn c-ι οο — ^ ^ -JCJO Oi r -J n oj cr Na -t ^ no oo

CO --- 1 h O CO OI CT5 O — 'O -P ^ Oi -P ^ O OO r- n — ^ O OO n O OO C rO CJJ —' ■ O — I CTJ — 'ΟΊ ΟΊ ~-1

O O O O SI O O Z O O O Z O O O Z O Z O

95 45

 ^^^^^ i— i— i— i— i— i— i— | — r ~

 ^ ^ ^ ^>>>: J> oi ji ri ai cn ai nnn ai nnn ji oi n ji ri cn ai an an ri ri cji n ji ji ji ai ri ai ri nn ji _ ^ _f ^ ccccccchhhh 1 1 1 1 1 OOOOOOOOOOO ι

 One c one o o o one o one o one o h c ro one o o

— ». Oo ^ ^ i co cn c h oo r r ai h ^ j o o¾ r co o oi o¾ r o r ^ o o one c oo o one -b.o o -P ^ r r o> o n

 σ> ^ I i o oi co oo oi i σ¾ ^ ι σ> ^ o i n ho o — ^ ο ο — *-co oo — *-o oo oo cn ho — »■ ι

III 1 IIIIIIIIIIIIIIIIIIIII IIIII t IIIII oo co oo-«oo --- — — ^k — ^ ooo --- io oo o oo ^ -j ^ j ^ rchc ^ n o>

— O »ro ji —» ■ r σ¾ i "ccco oo — * ■ <oo —» ■ — »■ ^ in o¾ -P». R ro — ^ rr> o ri -p ^ oo O "» -J a¾ co c »oco — · ■ --- ^ h o¾ o¾ -t ^ on -F ^ oo c --- One-σ> ro oo con oo <o —» ■ n --- ir oo — ^ ^ cnj ^ — ^ Cn rr co cj ^ -t ^ oo ocoor one-to-one r "p ^ o> no jLn i ^ ij j ^ nc cn o¾ nn oo o¾ h-« «J Ji o oo cT5 Co o> -i ^ o -"-^ i o¾ one oo one ¾ · 4 = * ^ 3 0 · ¾ ^ · ^ one an ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo oooooo one oozooozoozooooooozooo oooooo

1 1 1 ~ * ・ 1 o ≥k.o o o o o o

 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 o o

 o

 1 1 1 1 1 1 1 1 1 1 1 1 1! 1 1 1 1 1 1 1 1 1 1 1! 1 1 1 1 1 1 1 1 1

 1

 o

 o o o o o o

o

 o o o

 o o o o o

z

2

 o o o o o s o o o o z o o o o o z o o z o o o z o o o o o o σ σο ο οσ ΐ> c> m ο ο οσ> m σ c¾ one r h one ro one ho

 CT> C "> C"> CT CD C73

"" "" "" "Yeah ye ye" "" ""

ΓΠ ΓΠ ΓΠ ΓΠ ΓΠ ΓΠ ΓΠ ^ Ο ^ Ο ^ ίΟ ^ Ο ^ ^ o¾ σ> σ ¾ σ¾ σ> σ¾ ο οο σ> ο) ο>> ο> ο> ο θ) ο> n en nnn co occr rsj ho h rva iN one ~ * one one one one ooooooooo co co co ccoo oo oo ooooo oo oo oo oo ooo oo "-io> oo ro ro -i ^ nn cri cri oo <oo o ^ j oo n ro rr oo oi "-ir oi no o¾ ro one one oo r A one no ^ i ro o — ^

C ^ C O 00 C O tn 00 hro ^ ^ c one o one oo hco one <oo o5 0 nho σ σ> ~ *><oh one oo h

C ^ CO 00 CO

 1 rrh 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο co cccocccc rNd C roc ^^ co co co — tc D oi o cri oi o¾ o> ^ oo ji oo cji ji cri ^ ^ noco> c ^ oo h oo * -J oo o D Jir cn oo o 0> 0 00 0¾ ー One σ> One oo One --- One cc -J Oo ro occ an A One r oo One ho o> ζ ο ο ζ σ ζ ο ζ ο ο ζ ο ο ο

膽 5063 謹 1 1 1 1 ^ — ^-1 1 1 1

 瞧

 Ye

 One one one

 ? ; ^ ^ "" "" "" "" "" "" "" One "y>

 basket

 ¾ rv3 one one one one

 One ■ ~ '~ One "" "■ One

1 1 1 1 1 1 ^

 One one i one one

 One

 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

RND O Ji oi oi n ji oi co oi one -i

 One · ^ οο οΊ αι

1 1 ¾ ο 1 1

ο ο ζ ο ο ο ο ζ ο ο ο ο ο ζ ο ο ο ο ο ο ο ζ ο ο ο ζ ο ο ο ο ο ο ο ο ο ^ ο

 I

 膽

 I

麵

--j cj> cp o> o> o o¾ o¾ o> o> o¾ ai ji ai nnn ai ai ji ji ^ · CO CO CO CO CO o to oo --j σ> nzooooooozoooooooozoo oooozoooooozoooz σ C c¾ σσ S mm oo c> cs σσ> c οσ 3 · o> one one ho — ^ h — ^

 > One ― ― One One ― One ― £ Ϊ ^ Ω Ω Ο Ο Ω <<<<<<<"D ~ D ~ 0 ~ D ~ 0" O "O C¾ O C¾ £ 7> CO" "" " "" "" "" "" "" ": ^: ^: ^: ^; ^; ^; ^: ^; ^: ^" "" "

"O m rn m m m m m m cz c c c c c c c c:" "" "" ο ο ο ο ο ο ο ~ ~ <be σ> o¾ o¾ o¾ o¾ o>> o¾ o o o o o o o to o co o o to o co co co oo

<oo> c — *-oo Ts3 4 ^ c cn n — ^ oo or — ^ σ>-«■ J n -t ^ rn co n oo cri rs3 ι o σ> co ho n one r> oo oo one o¾ c ^ o ho nr 11-J O¾ o o¾ 4 ^ <o A ^ jo --jo> ji oo ho)

 c »σ> o — * · σ> h σ> i co —»-^ oco co a¾ — »■"-»-o¾ o-* JO co>-^ co co o oo. ro ~ -j ^ cn co oo o cn co ri o --J Co ai oo ocon oo cn one O O0 0 nor> one one co ai <one r ho or ro one one one one one one one one one one one one one one one one one one 1 1 1 1 1 1 1 1 1 1 co co — ^ o> oc ^ j o¾ oo oo oo c co o> ji r oo c <o o¾ — ^

 o σ> i ro oo r oo ho — ^ ji ai ji n i to co ai oo -j oi o oo os ro isa oi οο ο 4ο.n oo cy> oo n 4 ^ oco 1 --- ir co — ^-«Ι σ> σ> co ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooo co oo co n οο oo co one ^ i ji cn o5 0¾ cn on o> o¾ — * — ^ oooo oo ooo

o o o o o o o o o o o o z o o

麵 >>>>>>:

 ο ο ο ο ο ο ο ο ο ο ο σ σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο ζ ο ο ζ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ζ ο ο ζ ο ο ο ο ο ζ σ ο ο ο ο m σσ σ ο σσ> · mm σ ο σο 3> σ c¾ σο> ■

 One one r h one h one

 "I ~ I ~" "I ~ I ~" "l ~ I ~ DC> C C73 C73 C> CD C7>>>>>>>>" "<<<<<<<<<< 1 '1' 1 '-' 1 '1' 1 '1 CC

 「「 「「 「「 「「 「CO 0 0 O G C C

~ <~ <"o c o o o o o m m m m m m m m z z z z z z z z z" D "u ~ D ~ o ~ D" U "o

One o to

 σ¾ c one r r o oo r oo σ> CO CO CO

 o oo n o oo "» j oo ho o c oo c — oo ro «I

O

O OO 一o A oo

O OO

IIIIIIIII 1 IIIIIIIIIIIIIIIIIIIIIIIIII

 o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

OO —>-C0 ^ — — i jih n co oco co oico o¾ ^ on n co ji ~ p ^ co> oo o O "^ * -JOOOO co 00 0 ー ー 1 \ 3 0 one r o¾ <c co cn one

zozzoozoz: ozooo

.12, 1353153236.54400--ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ σ ο ο ο ο ο ο

52404.53232 · 6123.098 0023.--239 5 12.45531. 7934.170 0023 ·--^ ο σ ζ σ ο ζ ο ^ ^ ο ζ ο ζ ο>. 2 538 o 14.99033. 1433.746 0022.3--σσ> · o c¾ o co> Γ Γπ ο σσ> Ν Γπ σ ο σσ>

 r one r

 2 537 14.95132. 41731.44 02.506---<---<-<-<--<-<-<---<-<---<-<

5236 14.11132.2.7350 0025.--

OO QO OO OO OO OO OO OO OO OO OO OO OO OO OO OO OO 1 --- 1 I ^ J ^ -J ^ J 1 1 ^ -J «-J" "--1 --- 1" "- -1 -JI

IS3 3 - * · - · ■ - '- ^ - 1 -. 5235- 1.2861 4132.233695 0024. - - L - »- 0 0 0 0 0 0 0 0 ¾0 <0 <0 0 0 0 <0 00 00 00 00 00 00 00 00 00-^ I

 5234 12.4331.19 0033.854 0025.--

5233 1.57729.1.33632 0023.- 1

 5232.64711. 883294 0023.-

5231.53328.24 89,45 0027.--

5230 9.68527. 9442.9662 0025.--

5229 9.85429, 0441.7383 0020.--

5228 10.65128. 35.793056 0025.--

5227.68429. 4033.0 0023.--

522537030. 68527.8525 002. - -5226.454 81629.094 0020.-

522537030. 68527.8525 002.--

an -p>. o¾ c n r — *- ri o¾ ro 5224 12,78129, 53628.029 0203.--n — »· o co oo 1 oi oo <oo o N3 0 0 oo oo cji oo co r ji ND O¾ — * cr-». O — ^L 4> h cn cc oo nocc o>o> oo <O CT i rs3

an -p>. o¾ cnr — *-ri o¾ ro

 5223 17.66928. 75824.632 0036.--

5222 16.23929,24.570 0035,--

15.27428, 02924.823 003--22 50 13.84528. 3424, 447 00--

O Z O O 3 0 0 0 Z O O O O O O O Z O O Z 5 0 0 0 0 Z O O Z CD C3 0 0 0 Z O

 2194 5 13.0328. 97825.612 00--

5218 162711.3.938. 80000 0024.11

 5217.94427. 47827.31 135 0026.--

5216 1.35728. 00229.05 0031.--

14.78027. 15828.333 0029.--4 521798 69427.2504 002.- 1 523 18.33822. 03927.2054 003.--24 18.03423,45 039.0--211 7402 523,7.991 003.6--. 15827 16.12925.694 0032.--

5209.42. 6722 150058.603 0030.- 1

5208.4. 9072 1378228.395 0029.--2074. 992 5622589.989 0027.- 1 3 3 »3> 3» 3 »

OOO ooooooooooooooooooooo ooooooooooooss ≡

z o o o o z o o o o o z o z o o o z o

 5274 O C¾ 00 O CO O 0D> O O O GD> CD

> '' '' M 'm' m 'm one i ~ one ι ~ one one ― -o -D -a T3 -D T3 -o <<<<<<<<<<<«s:; omm rn rn 5273 ι ~ ι ~ 一 ι ~ 一 ―

 ι ~ ι ~ ι ~ ^ 33 33 33 ^ 3 33 ^ 3 ^ ^ 3 3 3 3 · · · 3 3 3-cs c c ci ci c c c ci m m rn m m m m m o o o o o o o "" "" "" "ι ~" "" "

0O 0O 0O O3 0O 00 00 0O 0O 0O C »0O 0O 0O 00 0O 0O 0O 0O 0O 0O 0O 0O 00 00 00 00 00 0O 0O 0O X) 0O 00 0O 0O ^. ^ --- 1 O Jl oh One CO ro 4 ^ CO C rs3 CO i h CO CO ho CO h CO i

Γ CO CJ1 O o cn r 5268 O CO o ai cn CO CO σ¾ o o Jl σ o CO o O CO

»1 CO n CO O o CO CO CO ho o 1 oo CO oo o O ooO ΟΪ CO CO o CJl oo o 4 ^ h oo σ> CO σ> O O σ> σ> ro 1 CO oo h 71 cn o

1 1 1 1 1 1 1 1 1 1 5267 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

CO CO CO CO O CO CO OO CO CO CO O CO O CO CO CO CO CO CO CO CO CO CO CO OOO CO ro CO CO O oo en σ> 1-»J ••• J"-1 o CO o <oo σ σ σ ro CO O cn Jl Jl-»j σ> CO ro ro to o oO <y> ro oo cn oo to Oi 4 ^-^ o oo ro O CO n N3 <ro o CO σ¾ CO 1 oo cn -J CO -J oo ro ro oo o O CO ro ho C oo -J ""-^ 1 "-1 o-^ l ro oo oo O σ> CJl cn o oo σ¾ O o CJl oo o σ> oo ro oon

 5265

 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

 4 ^ CO

CD o¾ <y> cn cn ro ro 5264O O ro h ho ο o o

 σ> CO oo CO h o o O CD cn cn <oo ho an o O o oo

 * -J oo o σ> <o CO CO CO cn CO Jl

 oo 5263O O CD CO ai O o

σ> cn O-"1 O CO <oo σ¾ σ> CO O Jl --j ho

 O ooooooooooooooooooooo ooo O oooooooo O ooooooooooooooo 5 o261 oooooooo O oooooooo ho r ro ro ro ro h ro h ro hh ro ro n C CO o O ro oo ^ 1 O CO o CO σ> oo σ> n σ¾ ■ 1 oo O CO oo oo

1 o o CO CO o CO σ¾ o CO oo σ> oo oo CO oo oi 3 no CO CO oo σ> CO oo CO O o ro CO CO CO CO on oo oo oo oo oo CO cn o o o ro o

z o o o z o o z o 5256 z o o o o o z o o

5243 謹 53

c z o o z o o o z o o o z o o cs z o z z z

 3> 3 ■ CD> Y N m C3 C> 0D>

"i ~ ι ~ ι ~ ι ~ ι ~ ^ a ^ o ^ o ^ ^ a ^ o ^ a ^ a a ^ a

→ → — I — I — (-<-<-<-C = (= C = CC = C = C = CZ---<-<3 »--->-C¾ C¾ C¾ C¾ C5 C5 £> C3 C5 C5 C5

(0 (O CO CO (O CO CO O CO U> CO O CO <0 (O CO CO C »00 00 00 00 00 00 00 00

hrrr — 'O ooooooo eo co eo to oo oo oo oo oo n 3i 1 l oo oo oo to oa —' cn jj tn j ^ o — 'OO to o to o rsD CO co c cji j ^ ^ OJ tn j ^ * .ji ^ ^ oo oo c «o co oo o oo c c35 c — 'oo r oi —' cn oo oo ^ cn oo ocr oi ho ri to o oo 1 r> -t ^ — J to rs3 0 ^ c co oo <o co N3 Ji cn — 'C 1 en co σ> oo co c-1 -i ^-^.-~-\ to ^ σ> σ> oo x> o —' <3> no cj >-^. ^. iv3 -l ^ -l ^ — 'O ^ to cj> o> or -― i to -p ^. —' to co-». ^ to —j-1 co —j σ> en — i oo h -i ». cn oo co n oj — JO ji ji co c r- oi C-ι oo en oi c o¾ --- oo o rso ~ 'oo cn

 '^ c cn o o ai o o c-1 1

 —> C oo σ> en ro-1 ^ rva c c α>-eo isa one rso one n one ^ one one ο σ¾

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

 4 ^ _ ^ "^ ^ ^ cri cri n cji cn n A cn cn on en-1 ~-1 oo oo σι ~~ ι en-~ σ» ~-1 σ¾ σ> on cn en »~ i po oo co o co oo o ui uj ^ & c — ^ o to-i a3 c ^. <3> s »cji oor 3 c ji 4 ^ o> cj5 — 'Oo oo —' r to tJi ^-1 iso en oi to-1 o en on oo — '^ 0 01 1 c cn oo o υπ-i ~~ j co to <one to one o 1 co —' rsa oc — ^ ho co iva to cn — 'C ^ rsa r cn oi O Oi O to i <o-^ cn o --jcccn c7>. ^ o) co <o <ooooooooooooooooooooo ooooooooooooooooooooooooooooooooooooooooo σ>> ~ jo ∞

O N3 <oro — 'oo tn o ^ — ¹ ~~ i to ji oo — ^ to or oo ri cri oo — ^ h -JO —' θ σ> ^ σ¾ O o on n <3i c »to to ^ cri oo rs3 c — 'O co oo-i cn c »co -l ^ ^ oo o cn cj c (o — ^ o ^

o ss ozoozozo cs zozzz

ooooooooooooooooooooo oooooooooooooo

o o o o o z o o o o o o z o o o z o o o o o o z o o o o o o z o o o σ ϋ σσ 53436> σ σ ο σσ> m σ σσ 3 rn r — ^ ro i h — ^

 「「 「「 「「

m m rn m m 4 r 535n '' '' o o o o o o c G m m m m m m m m m m m

5340

oi ji n ^ j ^ cji i ji to oo oo oi oi ^ on ji ji cj ^ ^ c ^ j ^ cji a ^-^ j i oo <o oo c oo o oo <o ho oo o oo ro

-«J o oo

 One oo a¾ 7 533 o r-«ι one-« i c r ^ oo oo oo co — ^ c oo --j T h

I I I I I I I I I I I I I i I I I I I I I I I I I I I I I I t I I I

 ^ 4 ^

 1 o co oo co oo co co oo 5336 hh ho ccc ~ i- o oo j> ji oo co cx> oo roo-^ — ^ ι οο c 4 ^ c an * »jco> o> cn o¾" ^ー 00 ooooooooooooooooooooo ooooooooooooooooooooo ooooooooo 5333o oooooooooooooooooo

OOZOOO 2T OZOOOZOCOOZOO

oo h r one to o one ◦ "■ • ■ t ^ c oi j ^ ^ .c .c ^ fsa .co jj jj jjO f fsa i ^ O ^ o o rNa rsj r

— I ^ o oo oo cji o cn o oo o — 'Γ-1-1 c ~> · σ5 θ οο ncc one t- tsa oo-1 —' c σ> to c ~-1 one cj ^ ~~ cn cn o> hro o¾ ji ». oo en a5 — '— ^ι σ ^ <ο σ>σ><ο CTJ tn tO CO Oi OO OO One' OI OG rsj J ^ One J! k O One o to tva one c ^ ccoo -— I to-Ι ΟΟ ΟΙ ϋΊ

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

 c c c c c c c c c c c c c c c c c c c c c c c c c

 0 (0 (0 o-^ con oo oo -p ^ ri oo ~~ i cn ^. O -P »o — ~-'hr cn ^ o —' oo o oo tri c ^ ^ j cn i <o i

 to y o-~ ^> ^ ο Γν

5 o ^ 9>; · ^ 5? 55 σ> ^^ y ^ gj ^ j ^^ oo ^^ gj P oo? 55? ¹ ooooooooooooooooooooo ooooooooooooooooooooooo ooooooooooooooooooooo ooooooooooo rs3 co oo < o oo 1 σ> ~~ I σ> ~ »l oo n oo c ^-^-^ rc ai o -c ^ cc oi ~-* — 'o oo-~ j oi <3>r> o) c- p ^ σ> c-coin to rsa oo ^ j — ^ ^ ^ — 'c co r <o>>> j one co co h oo to or> 05 σ-en oo> h — ¹ o "-ι σ> One ^ One ~-i co co o) na> n-^ <o-cn

ozoozoozoozoooozooozo o

6 1

0 / L 00 I 020-039 κ- m 21 01 α 1VA aoV

0 8 O τι 00 L m • Ofr- ιζζ 9ε- 018 LI O 01 α 1VA vo l s 隱

N 6fr ZZ 00 I 939 • 6S-8L9-Oil • 81 O 01 α VA N 0 s IN01V

0 63 ZZ 00 l m • 8S- ILZ SG- [LZ • 9L 901 α a s 0 WO 丄 V

0 L ZZ 00 l 999 '8S- m κ- 93ε Li 901 α 0 W01V

0 ZZ 00 l no '9S- 99ε 81 901 α 90 L WO 丄 V

0 Ifr 00 l 1319ε- 868 ε- m LI 901 α 90 讀

0 ZZ 00 ■ I 663 B ε- 996 εε- 86 B a 901 α ms vo 1179 WOIV

N L9 ZZ 00 ■ I 9SI B ε- ^ 89 ΖΖ-6U Ll 901 α N V

0 LZ oz 00 l B 86 ε ιι-- 886 901 α 311 0 WOIV

0 69 ZZ 00 I 090 O ε- 039 ιε- m 901 α 311 0 z WI01V

0 08 63 00 l 0 6ε- 923 LZ- U9 • 91 901 α 311 ιαο WOIV

0 81 82 00 l \ π 8ε-B 01 "83-6017" 91 901 α 311 190 0L½ WOIV

0 O 0 9Z 00 l 8S9 6ε- 961 οε- 9 O 8 91 901 α 311 290 60 ^ 9 WOIV

0 S B 9Z 00 l 9LZ 8ε- 8 ^ 63- 903 LI 901 α 3, l ao 80 ^ 9 WOIV

0 08 ZZ 00 l 810 B ε- 892 οε- S68 • 91 SOL α 3 1 vo B 0½ WOIV

N 93 Π 00 • I 86 B • SS-GS9 '63-981 LI SOL α 3, l N 90½ WOIV

0 S8 n 00 l B 90 Z9 QZ- 690 SI SI α DdV 0 90 ^ 9 WOIV

0 39 n 00 • I B 06 π- m "63- LZZ • 91 m α Dyv 0 WOIV

N 0L 08 00I 0C- 88 'εε- Hi LI m α Dyv 3HN 隱

N Π ZZ 00 • I B 61 08- L8S 'εε- SS 61 m α ayv IHN WOIV

0 19 Ζ 00 • I 669 08- 101 88- • 81 m α 9yv ZO IN01V

N IL ZZ 00 l • ιε- 9803G- 668 LI m α oyv OOfrS WOIV

0 90 oz 00 l m • ιε- ou ie- m '81 m α ao 66C9 WOIV

0 99 QZ 00 l 996 ζζ- L9Z OS- on • 81 m α DO 86E9 WOIV

0 99 9Z 00 I 689 ζζ- SOS "63- m LI m α ao L WOIV

0 Π 9Z 00 • I L99 • εε- 8392 Ζ- 399 • 91 m α vo 96S9 隱

N 39 9Z 00 l 691εε- 218 3- SOSSI m α DdV N 9689 WOIV

0 69 ZZ 00 l 169 π- 16093- 389SI εοι α V1V 0 WOIV

0 6S 00 L 969 • εε- "9" 93- L80 ■ SI εοι α V1V 0 WOIV

0 00 I B 8 • εε-Z9L "93-869 ■ zi εοι α v, v ao 3689 WOIV

0 93 00 I 931 • εε- m '-ι εοι α v, v vo 16SS IN01V

N 99 93 00 l LZiεε-89 Π-699 ει εοι α v, v N 06S9 WOIV

0 1 ^ 6 LZ 00 l QL0 ζζ- 83ε η- S9 • si 301 α y s 0 68S9 WOIV

0 03 83 00 l 829 ζζ- 806 11- L99 • 301 α ms 0 88C9 隱

0 06 00 ■ I 669 ■ οε- SS B οζ- LIL XL 301 α d3S 90 L WOIV C00 / .00Zai / X3d 6 8 £ 0 / 800Z OAV 5 5 5 5> 5 3 3>-5 5 ooooooooooooooooooooo ooooooooooooooo

 z o o o o o o o o o z o o o o z o o o z o o z o

 5454 h h one> ro one

—I —I

 5453 m m m m m m m m "" "" 1 1 1 1 1 1 1 o o o o o o o o o o o o o o o o o o o o o o <o o to <o oo oo oo oo oo oo oo --j-»-j-»-j-^ j

— »· — ^ H r ho r r r 5449 o r —» ■ —

 c oo co oi j ^ c o c ro one o co oo oo A

 c ^ ^ * «J O¾ oor 5448 ~» "οο σ> o oo ro c o¾ o¾ co one chno! ^ r one 00»-€ Τ> θ σ> σ *-n Jl 3 3 CC 05 C0 05 tO OO CO C OO J ^ — »-O ^ I ^ I OO OC oo oo

 n h rsj --- 1 to n o Or

-- 一 一 to oi o -—i o

-Ichiichi to oi o -—io

 I I I I I I I I I I I I I I I I I I I I I I I I I 1 I I I I I I I I I I

 ^ ^^ ^ 4 ^ ^ <^ oo o-«j co-^ ^ cri o> o> o¾ cn i 44 54o> h co n cr> oi ji cc ro ooo one oo one r co oo co --- o co oo σ ~ »·«-1 n σ> r oo n ~ * · σ σ 1 oc <o σ>-^ ^ o one ro one οι <~ · Γ \ 3 θ one o one <c 44 53 co «

 --J h to o rsD i rsj -joo-^ oo — ^ coooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooi -f ^ oo ^ J 3 n oo oc o¾ oo-* J o> ri CT> ^ JO c — »-to-^ o¾ o ji ai o ji --- 1 ho oo o 1 oo

Z O O O O O O O O O O O Z O O O C O O O Z O 5436O O Z O O O O O O Z O O O O

4 523 0 GLU D 1 ATOM 549415227.58

 GL ATM 54930U D 1152O2.252

 AT420E2 GLU D 11OM 59523.402

 I I I I I I I I I I I I

 00 cn oi cn cji cn cn oi oi ji oi tn oi on ai oi ji oi cn cn nn oi oi nj ^ 4 ^ ^ 4 ^ 4 ^ n <o an cn o CO o ο ro CO on Jl o σ¾ ro σ> 1 σ> h cn CO Jl o an oo ay oo o ro ho h CO ooh CO ho CO oo cn σ¾ oo CO cn o oo OO o σ> o σ¾ σ

1 1 1 1 1 1 1 1 1 1 1 1 1 1 n cn cn cn CJl CJl ai n n n on n

1 mu c

CO O CO o O oo n o o oo — 1 CJl on O O oo cn to O o cn ro cn oo < > cn o CO σ oo σ O ro CO C σ oo o cn σ¾ σ> ooo CO ho ro ooooh

CO O CO o O oo noo oo — 1 CJl on OO oo cn to O o cn ro cn oo <> cn o CO σ oo σ O ro CO C σ oo o cn σ¾ σ> o

-o oo cn ai σ> o <oo σ> h σ> o cn r * ooooooooooooooooooo O oooo O ooooooooooooooooooo o oooooooooooooooo Jl CJl σ¾ σ σ¾ ΟΊ cn n CJl cn σc cn cn cn σ> σ¾ CJl on an cn ho o oo cn CO ro CO O o σ> CO o CO C CO o O CD CD rs3 o O oo ^ 1 ^ oo o oo cnc ^ ι one one or ai one o ~ ^ oo ono oi rch oi o¾ ji oo ^ 1 0 one oo ai n

o o o o z o o o 3s: o o z o z o z z z

4 NH ATOM 5 or 2 ARG D 11213.987

 4 NH1 ATOM 565 ARG D 15.887

 44 CZ AR ATOM 56G D 11214.837

 5463 NE AR ATOMG D 2 214.633

 AT 5462 CD AR DOMG II 2

 AT 5461 CG ARG DOM II 216.589

B ATM 5460 C ARG D 1O1217.678 A AT 5459 C ARG DOM 11218.720 ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ σ ο ο σ σ σ ο ο ο ο ο ο ο ο ο ο ο ο z —i ee

 rsa r r rNa r 1 1 1 1 1 1 1

 o o o o o o <52 <5o to co o co

552

 CT

00 n ji oi ai ri ri cn ji n ji cri nn oi n oi oi oi n ai ai oi oi cji cji oi n oi ri oo co oo <oooco — ^t rrn ^ ^ -i = *> cc ^>o> Oi Oo <o «I --JO>O> O¾ CT nho ^ oo co 1 ro ro o en c ^ — ^ oo σ> oo i ^ oro oo ro oo — ^ conh — ^ ji cn

 -*. o n c ji o o h n h o n n <o> -Cfc.o o ji ^ o

I I I I 1 1 t I I I I I I 1 I I I I I I I I I I I I I I I I I I I I I I

 4 ^^

 c h ro ro-· "-i o> ji o> oi n n one r c c oi one c r cn --j o> a¾ o¾ o¾ a¾ oo

ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo oooooooo oo n i r i ^ J O¾ C OO O N3 0 o¾ rc Γ σ¾ οι σ> i coo i ^ IJ ^ CO C i cn co oo σ ji --- ¾ ich ^ oo ro — ^ oo co oo — ^ o oo — *-o --- 1 o <n ""--1 --- 1 ""--1 no

0 0 2Ϊ Ο Ο Ο Ο Ο Ζ Ζ Ο Ο Ο Ο Ο Ζ Ο Ο Ζ Ο Ο Ο Ο Ο Ζ Ζ

5495 ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο o

-J

 o z o o o o o o o o z o o o o o z o o o o o o z o o

0039 ooooooooooooooooooooo ooooooooooooooo

ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooocccccccccccccc ccc A ccccccrr ^ ro cco an ^ ^ one ro ^ ι ro co io cx> cn oo oo oo ro oo co rj ^ oo o co co jooo -o ^ oo one oo one one one O

SE OOZOOZOZOOZZOZO

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> ooooooooooooooooooooo oooooooooooooo

 o o o z o o o o o o o o z o o o o o o z o o o o o o o z o o z o o o o σσ 3 m m σ σσ> ■ σ σ σσο 3 o Ω Ω co> · σ o σσ 3

 4 563 ro 1 r 1 1 1 o r 1

 ; 3σ; σ; σ; ο "5633" "" Γ "" "" ο ο ο ο ο ο "" "" "c / 5 C / 3 C coooccccc co cccoccccccccccc Go c GG c G crrrrhroccc ro rh 5631r ro ro rhr oooooooooo co oo to o

o oo oσ> 5628 ooo <o

o oo o

00 CO CO CO CO CO CO CO CO CO CO

 — »■ ro σ> σ> I O¾ COCC ^ JI 5626 <—»-r ^ oo cn I OO CO *-^. Or cn r — ^ ο Γ \ 3 απ --ϋ σ — »■ O σ> c ~ o ro o ro c --- ir> rr> ^ cn co rcroocno — ^ cn — ^ 4 ^ c oo r ^ r oo ai o co co i oo --jo> ji oi oc --- J OO ^ cra co — ^ oon oo cn co — *--t ^ --- 1 — »■

I I I I I I I I I I I I! I I I I I I I I I I 1 I I I I I I I I I I I I 4 ^ on n on ^ on o o oo ^ J5 jn c 5624c r ^ r r c r ro c — ^ c j ^ n n o o oo 1

¾ ri 4 ^ co * -J c cn r <o i o>-»J 4 ^ o¾ i OO con i o¾ oo ifc C o> on — ^k ^ o¾ ji o co ro 4 ^ <o <oo oo ro — ^-^ j -pk — * ^ 1 c -P *. ι n en -J o σ> σ σ> nco ι σ> ho o ^> 5623 ^ o> n — ^ ^ r oo c o¾ ^ j oo- o oo oo 1 CJ ho o ro ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo oooooo ο one c oo o¾ r o5 05 00 one o ^ iJi po j ^ po oo c απ σ¾ σ> r cy ro — *-oi "-ro oo o ""--i ^ J hch ji one cc ^ jocc 1 — ^ c <o oo _ρ ^ σ 4 ^ οο θ ϋΐ 一 NO OO C OO O one --- 1 oo h isD one OI-»J One h ^ ι οο σ> One cooo oo ο ζ ο ο ο ο ο ο ζ ο ο ο ο ο ζ ο 5616ο ο ο ζ ο ζ ο ο ο

5603 981

0 9fr OZ 00 ■ Λ 8Ε0 6S- 388 9ε- 96 O • 9 LZ l α 311 0 ^ 99 ■ V

0 08 OZ 00 Λ m 6ε- LL6 se- 310 ∎ 8 LZ l α 3, Ι 0 ε 9S W01V

I/IIOIV0 O 9 OZ 00 ι 98- S90

I / IIOIV

0 19 L I 00 ι 098 "98- 669 8ε-B 09 • 6 Li l α 311 LDO l B 9SV

0 • 61 00 Ί m "68- 91L 8δ- ZZ l • 6 LU α 311 390 0 O 9S ■ V

0 93 ΛΖ 00 Λ 386 O ε- 990 ■ 8ε- ■ 8 LZ l α 3, Ι 90 6999 ■ V

0 • 61 00 Λ 390 `` 88- 039 9ε- '8 LZ l α 311 vo 8999 I / IIOIV

N M 00 Λ ε ^ 8 9ε- W) 6 "98- m • 8 LZ l α 311 N O 99S

0 OZ Π 00 Λ 910 LZ- ε κ- 8 6 981 α Π3Π 0 9999 IIUOIV

0 176 ZZ 00 ι 9ε- 9ZL κ- 938 • 8 981 α Π3Ί 0 9999V

0 9fr OS 00 ι 39ε η- 9 • οε- 8 • 9 9SI α Π3Ί ZQ W99 ■ V

0 LZ ΛΖ 00 Λ 9ΖΖεε- 998 2ε- ■ 9 9ε L α Π3Ί ιαο S999 W01V

0 89 '62 00 Λ 39S κ-981 ζζ- 699 • 9 9C I α Πyo, DO 3999 WOiV

0 93 93 00 Λ ιζ “98-B ιζ-B 9 • L 981 α Π3Ί 90 1999 W01V

0 03 n 00 Λ 69 L S8- η- 181 • 8 981 α Π31 vo 0999 WOIV

N S ZZ 00 Λ η- κ- 061 • 6 981 α Π3Ί N 6999 WOIV

0 89 OZ 00 Λ I IL ζζ-9ε- B 90 • 8 SS I α ν, ν 0 8999 I / IIOIV

0 99 ZZ 00 Λ 900 • εε- m κ- ZLO • 6 SS I α ν, ν 0 S9S I / IIOIV

0 O 9 00 • 1 VLZ ζζ-8 O 0 9ε- ZO l U SS I α ν, ν ao 9999 I / IIOIV

0 96 00 • 1 8 B 0 ζζ- 818 κ- ZLZ ■ 01 SS I α ν 、 ν vo 9999 ■ V

N 66 9Z 00 1 10L 'οε- IZL κ- 918 ∎ 6 SS I α ν, ν N WOIV

0 n ■ OS 00 1 0C- 89 ζζ- οεB ■ 01 α 丄 0 £ 999 WOIV

0 11 • οε 00 1 m "63- εε9 810 01 α 丄 3W 0 3999 ■ V

0 9S 9ε 00 1 • οε- εεβ • οε- 336 S α 丄 3W 30 1999 隨

S 9ε 00 1 019-ζε- S S α 丄 il as 0999 ■ V

0 9S ε8 00 • 1 so B-B 6ε εε- 600 • L α 丄 90 6 ^ 99 I / IIOIV

0 31 ic 00 L ZZL-938 ζε- 900 • 8 α 丄 HI 8 ^ 9 ■ V

0 01 • οε 00 1 919 '83-919 ∎εε-60S • 6 α 丄 3W vo Lm WOIV

N Ifr • οε 00 1 l B s LZ- L90, εε- om 01 α 丄 3IN N dm I / IIOIV

0 81 00 Ί 396 "93- 991 ■ 6 εε ι α 9dV 0 9 ^ 99 INOiV

0 \ Z ιζ 00 ■ 1 ιοε "92- 998 ■ εε- 806 ■ 6 εε ι α OdV 0 ^ 99 INOIV

N 6 ζζ 00 1 1 913 π- ΖΠ ζζ-6S9 εε ι α DdV HN zm WOIV

N I ζζ 00, 1 993 "93- 668 ■ εε- ■ 9 εει α LHN z WOIV

0 90 ζζ 00 • 1 88S π- ζζ-9S8 '9 εει α ZO i WOIV

N 9 '63 00 • 1 m-m ■ is- 8S ■ 9 α om I / IIOIV

0 L9 "63 00 1 m-696 is- 661 • 8 m α 9dV ao 6G99 WOIV

L08 £ 00 / L00im / 13d 6 8 £ 0 / 800Z OAV ooooooooooooooooooooo ooooooooooooooo

 O O O O O Z O O O 0 O O O Z O O O O O O Z O O O O C5 O O Z O O O O O O Z o o σο · m o c¾ σσ 3 σσ> ■ σ σ ο σσ> Ω GO r 1 5706 ho — ^ h —

"" "" "¾ 3 3 3" 0 "0" 0 "0 -0" 0>>>>>>>>

 m m m m m 5705m m m m m m m m m ^ D ^ D ^ D io ^ D ο ο ο ο ο ο ο ο

 C C CZ CZ C C — (— 1 — I — I — (— 1 — 1 0 0 0 0 0 0 0 "O -0" T3 T3 "D -D -D -D

4 ^ · ^ _ | ^ 4 ^ ^ ^ ^ ^ ^ ^ 1 5703 1 1 1 1 1 1 o o o o o o o <o <o o <o co co <o <o oo oo oo oo oo oo oo

o o no> co 5700 o oo o> c o¾ cri --- 1

oon

I 1 5699 I I I I I I I I I I I t I I I I I I I I I I I I I

00 4 ^ ^^ O C C C C C C C C C C C0 C * ^ C C C C C C 3 C

 c c ho h one one one o co co o co oo --- σ> σ>-"-ϋ σ¾ ο οο ςο οο σ σ> σ> ςπ ο Γ

 3¾ 4 ^ ji o o o c 4 ^ 5698oo ^ -j c ji r co co ji o oo -p * .o¾ r 4 ^ co —-o oo r --- i cn i n O

 oo i o r j ^ ^ n ho oo cn-^. c ^>-^> — ^ o oo o c i o> c o <o one co one h t "-1

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

_ »· ΓΝ3-■ I ― ^_ One 5695 · —— One ——-—— One ho ~ '― One" ^— 4 ^ ooooooooooooooooooooo ooooooooooooooooooooo 5693o ooooooooooooooooohrrc ccccccc ro hr ro rrr ro rrccccrr ho ho ro lohc ho r oo one oo oO "^ o> n an o¾ 05 0¾ *" j "P ^ oo> oi ro 3 0 one c one one oo one oo one ■ ^ ■ f ^ r oo od C r cn o oi AOO cn h co oo o an o ji oa ^ un a

o o o o o z o o c z o o o o z o 5688 o o o o z o o o z

5675 ooooooooooooooooooooo ooooooooooooooo ^ ■ ^ ■ ^ ■ F ^ ccccc co co hhrhohhhrh

 z o z o o o o z o z o ^ o o z o o z o

 CD 3 cr σσ 3> 3 σσ

 ">>>>>>> Rn mmmmm" "" "" "" ェ ェ ェ 「" "" mm rn "" "" "" ": ^: ^ ベ ベ ベ ベAll: = o: ^ iO; ^; c jD D>>: E>> cc

4 ^ 4 ^ ^ ^ ^ 4 ^ 4 ^

 C 00 00 00 00 00 00 00 --- 1-"---- io> c7> c7 c7 ji oi ji ncccc ho r oo co oo σ> σ> ι οο οο —»-ooooc co co oo lj ^ j ^ co co j ^ cn co co i rcr rva o ho h I oo IO 01 00 OO i c ^ ccco oo c oo ro> i Oi ccc i r rsa coh

CJl "-^ o¾ c j ^ cy <c n o o c 3 C-« j oo — *

 00 ^>

00 I-k CO CO oo cn cD --- 1 oi

 CO CO O-k> CO -P *> ^. ^ ^ OO CD One CO o o — ^

o co co co ro h ^ O->-Pk> 1 co o-*-J en ^. 1 co o co σ>"-io« -j o¾ o cn <3> 0 0o o¾ o «^ j oo co o oi AO c oo one co ~ * "0-» j an ri ^ a "i one σ ^ οι one oi oo co co tj ^ co oo o oo one ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο h ho hhrro ro rhhoc ho ccccccccccccccccccc oo en rsj oo co n σ

o co co

ζ ο ο ο ο ο ο ζ ο ο ο ο ο ζ ο ο ο ζ ο ο ο ζ ο ο ο ο ο ο ζ ο ο ο ο ο ο ο ο ο ο ο ο

ο ο σ ο ο ο σ ο ο ο ο ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο oo oo oo

 h one o

 Z O O O O O O Z O O O O O O Z O O O Z O O O Z! O O O O O

 σ σ ο σο> σ σσ ■ ο ο σσ> σσ> o o σσ> ■ J — ^ One ISD h One One O

ο ο ο """""""""""""""" c ^ ^ "0" D "u ~ D" O "o rn rn m rn rn rn rn rn ^ υ>>>>> ΓΠ ΓΠ ΓΠ ΓΠ ΠΊ ΓΠ ΓΠ ccc co c ^ rh ho ho ho hh " ¹ " one one one one one one ooooo <o to <to <o

oo o r o one co o one n one 4 ^ € θ ΓΝ3 Γ \ 3 · ^ ^^ σ¾ Γ-Γ αι · --ι οο ONE "<<» j c co ~ ^ h

 o — ^ a cft oo h c — ^ €> ^ ο σ — ^ «ι σ> ^ ai o¾ ai O h ~ *" cri o> o oo

 CO

 r one o oo o — * "4 ^ one σ¾ οο one onc one o one h one oo one r oo oo>-« jr one ai co> «^ co> h one r o¾ o oo cn oo o¾ 4 ^- -1 rsD oo n --- 1 -t ^

I I I I I I I I I I I I I I I I I I I I I t I I I I I I I I I I I I I I c r o — ^ oo o c

 CO o oo a¾ o oo c cn o o5 Ji <ro o> o> ^ ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooo on oo 4 ^. Nl oo — »-oo ho> o — ^ onoo-^ c —-an c — *- o> h "-—»-oo-^ oo — '-^ oo c

ZOOOOOZOOOZOOOO SE OOOZOOO

ooooooooooooooooooooo ooooooooooooooo

 z o z o o o z o z o z o o o z o o o o o one r one h one

 m m m m m m m m m m m m m

>>>-<--<-m m cri cn cji cn ri ri ri ai ri ai ai cn cri ai cri cn on cn ai ji ji cn cri oi ri ji ri n oi ai cn n ai cri oi cn

OO OO OO "-^ I" "--1 --- 1"-■ «I ^ I-^ J"-1 l ^ ^ O 0¾. 0¾ 0> 0> <3> 0> 0¾ Jl CJl CJl CJ1 CJl CJl CJ1 0l ^ ^ 4 ^-^ ^ -F ^ -t¾.ro

 o One ^

 σ> σ¾ οο σ¾ <ο-^ οο Γ --- 1 ο --- ir <o o¾ * -J one oi o¾ oo ho a¾ oo cn ji ι co oo o -J <--- 1 co en co co ro i «-j ^ o oi co i o> o i co oi --j ai ^" p ^ ai on ^ ~ ra »oo o i oi ai o oi <o« t ^ i σO 4 ^ 4 ^ ^ J ^ A 4 ^ ^> ^ 4 ^ 4 ^ 4 ^ CCJ ^ AAAA

 r r o> ji ji oo --j o> ^ i r 5806— ^ n — * h o¾ cy — ^ co

 o on n j¾. n ji o¾ n -P * .co ro oo oo — ^ co c ^ o —

 o> O oo "-j o¾ co <o —»-oo ^ O "-J C o ri cj5 C

IIIIIIIIIIIIIIIIIIII 1 t IIIIIIIIIIIIIIO CO OO CCO i OOO 0 * ^ J <5804t t O <OO CO; ~ i (\ J fSJ C rN3 ri-"J O5 O> σ) 4 ^. ^ Looc — ^ O 3 Ti -i ^ oo <— ^t <ono o¾-* j --jo ro r ^ — ^ ho oi oi --- 1 σ> an n σ> oo ^ ji r ^ ^ <co o5 c oo ^ co oo oo D ^ co ^ o ji ji oo oi c ^ c ro oo a¾ t ^ ι ai one σ¾ one oo rsa c oo c ^ jcc 5803 oi oi h one ai co co ro ^ -jnr one c-»J O¾ OC O¾ ooooooooooooooooooooo ooooooooooooooooooooooo ooooooooooooooooooooo oooooooonc oo one oo oo co o> one "^ one oo oo o os ^ ^ J-* JO <OC O> one o¾ o ai <oo or r> no one an o o¾ roo o¾ o rs3 one cn hj ^ och cj A os n ^ oo oo oo oo oo

ο ο ζ ο ο ζ ο ο ο ο ο ζ ο ο ο ο ο ζ ο ο ο ο ο ο ο ζ ο ο ο ο ο ο ο ο ο

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o O

 : t n oo οο

CO

 cn oo — *-r o oo CO

<O co c oo oo CO

<O

 IIIIIII t IIIIIIIIIIIIIIII t IIIIIIIIIII oo o¾ co h oo oo co oc oo ^ jo oo ^ incoo co co ^ 1 o σ cn ι-ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo oooooooo ^ h ho rh hor rocc hoc ho hho oi ho oi h-^ OJ-^-^ ^ -J on ro — »-oo oo o oo" -jhr-^ oco ι n -J c ^ ι cn ι σ -ρ ^ — ^ o — ^ oo o ^ -J h »* · ^ ι h oo co oo ri oo ho> r oo ^ jc ^ r oo o¾ o oo c ^».

ooozooooooozoooozoooo ozooooo zr oozoo

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

 C C

31.- ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο

 0 0 0 2 = O O O O O O Z O ^ O O Z O O Z O O O

 ϊ rn rn σ οα c¾ σο> σ σο ο ϊ>

"" "" "" "" "" "^; Σ ^ σ ^ σ" "" "" "" ">>>>>> ■ <>" <c = ccc: cccccooooooo>>> >>> ">>>" "" ""> O ¾ 4 ^ oooo co co co co o

I I ί

 o o o o 丄 ro

o — ^ n o¾ co ro oo <to o-^ co nr --- — ^t o oo D '«-j ji ^ J cri oo c oo rND <^

 CO CO --J OO OO--^ 0¾ ー 00 One c-»-j-" * nrcc oo 3 c — *-o <— »-n ι c cx> ^ σ --ι · ^ οο One o co o oo n one c oo oo oo --- io> oo c co n

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I IO

I --J OO CO CO i O — * o co οο oo οο --- i «-j o¾ o¾ o> nnn ^ ch ho O CO""-« I oo oo ro — jro — ^-^ rc oo ι -c ^ oo — ¹ oo — ¹ hi o¾ <oo oo c o5 ji ro oo cn oo oc — ^ oi r> ~ ^ one o jj roo one--j 1 ro o "-1 — ^-^. n ho oo t cj -j oo — ^ o> cn -t ^ on co ^. <i *.

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I ^ 4 ^ ·· ^ ^> 4 ^ ~ ^ ~ ^ 4 ^> 4 ^ ^ <^ ^ ^ One r co r co! ^! ^ ^ jj "i ^ j)) ^ (7> ^ ji oy o> co c oo --j One O One 0> 0> 01 4 ^ 0¾ 00 01 0> ^ 0> 0¾ ー One r * cn oi rxa oo ai o ji A c 1 h cji n οο σ οο σ> one one θ ϋΐ ο οο ι ο σ * »-one σ¾ o> --j o¾ ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooo

^ co co ^ c co cn ri cc)-^ o> o> c3> oo nr oo ^ ^ nc cn rc -f ^ 1 4≥> · h oo-^ σ) on — ^ co -p ^ .o ro co "-· ic oo ooro> c — ^ ^ ^ co oo ho c co h ^ oo o-^ 0) 0o oo <— i- c

ooozoooooooozoooooozo ooozoooozoooooo

3>-3 3>>-3> 3> 3-3> 3> 3> 3> 3> 3> 3> 3> 3 D> 5>>--3>

— Ί —1 —1 —i — H -H —1 —i -H -H —1 —1 —1 —1 —1 —1 —1 —1 —1 —i —1 —1 —1 —I —1 —1 —i —1 —1 —1 — i — H —1 —1 — 1 O ooo OO oooo O oooooooo ο O ooooooooooo O oo ο ≤:

n cn cn cn cn cn J1 JI JI ai n cn an cn JI JI an cn cn JI JI JI ΟΊ cn cn CJI CJI CJI CJI 71 cn CJI

CO O CD CO <OO CO CO CO CO CO CO CO CO O CO O CO OO CO CO CO O CO CO o <o OO CO CO σ> σ> cn cn Ol J1 cn cn cn JI an cn--f ^ CO CO CO CO CO CO CO CO OO CO ro ro ro to o oo-^ 1 cn ^-CO ro CO oo cn CO ro OO OS cn CO o O oo ooo O ooo ο ooooooo

 O o o m m Ω σ σ CD CD o> ro T ro

CD o CD CD CD>>>>>

 I- I- ΓΠ ΓΠ ΓΠ m m m m m I- J— I- o cz d cz cz c = cz cz m ΓΠ ΓΠ m m m ΓΠ ΓΠ σ σ σ O σ σ

oo 1 -J -J ""--1 -j

o CO CO CO CD o O CO oo oo 00 oo oo oo CO CO J σ> σ¾ OS σ¾ σ¾ cn JI CJI CJI cn cn cn JI

1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 .1 o o o 4 ^ O o O h ho ro ro ro ro ro o o o ro 3 ro 1

 CO D

 oo -r ^ oo CO oo CO CO O σ> CO ro 1 oo o ro o -J CO O oh σ¾ o 1 CO oo cn o OO oo CO ro cn CO σ¾ CD o σ> PO o o¾ cn oh ai O CJI σ --- 1 oo σ> oo CO σ> o CO CO ho> O o oo cn ro σ> cn cn ro σ> O ho O-»J

1 t 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ((cn ^ an JI cn CJI CJI an ^

o CO CO oo oo σ¾ oo o O o o o o o o CO oo CO cn σ¾

T ^ σ> 4 ^ ro-»j oo --- 1 oo CO o cn ro CO nh O JI CO ro ro n ro r O oo ro ro σ> ΟΊ oo CD O CJI CO CO ho oo hoo CO oo 1 JI σ¾ oO-«jo σ¾ σ> --j σ> CO • ^ J -JO ooo σ> o-» 1 oo O JI oo O oho σ¾

1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

CO O CO CO CO O CO O CO CO CO CO CO O CO CO CO O CO CO CO CO CO CO O CO oo CO

 h cn σ JI CT 1 n '"-1 1 --- 1 oo« "-1 oo o CO O oo o CO o oo <o O o ο

CO O CO CO-»jon N3 OO CO σ> • * -JO σ CJI ro an COO cn oo ho σ> oo CJI o CO oo oo ho CO CO CO O CO cn σ C oo -j CO" "-« 1 CO

-»J ho CO ^ cn O ^ O o ro oo ^ cn σ> o cn o CO K5 o cn o 1 σ o CO oooo O oo O oooooooooo O ο ooo OO ooo O ο oooo ο ooooooo O ooooooooooo ο oooo OO ooooooooo ο o

CO CO CO CO CO O O CO CO O CO CO O O CO C CO CO CO ro CO CO CO CO O CO CO CO CO ro ro ro ro

¹ 1 oo σ> O oo cn ro CO CO cn CO O CO CO ro ^ 1 CJI C CJI CJI CO σ¾ O 1 CO OO o O oo σ¾ oo oo ΓΝ3 o cn σ> 00 o oo rh ro CO oo CO 1 o oo -J to CO CO O ο cn o ro ro cn CO O ro ro oo O JI ο ^ oo oo CO CO oo ho O oo ^. o

ooooooozooooozoozoozo ooooo

o o z o o o o o z o z o z o o o o z o o o z o z o o

C3 C3 C5 OD 3 »£ 71 00 3 C3 mm C3 C3 C5 00> CO 5» N m C3 C5 0D> r>

 --3> 3> 3 3 -α -α τ3 -σ -σ -σ -ο

 -<-<-<-<-<-<-<-<-O Tj -σ -σ -σ -σ ο ο ο ο ο ο ο <> GO GO c oo c c

∞ ∞ oo ∞ ∞ ∞ ∞ ∞ ∞ ∞ ∞ ∞ oo oo ∞ ∞ ∞ ∞ ∞ ∞ ∞ ∞ ∞ ∞ ∞ ∞ ∞ ∞ ∞ ∞ oo ∞ ∞ ∞ ∞ ∞ oo ■ pk jik ■ kj ^ cccoccc rva rva rva rva rva rN rj rsa rsa r one one one one oooooooo cn ja- tn j ^ oi ik C h S one o one OO cj oi cn iva rsj — 'O <onc to o¾ rs3 ~-1 oo> —' en

 oo — ^ co σ>> σ> o — ι ο θ — ^ co

 oo o co o o -t ^ ~ ^ n i oo o oo-~ j c oo oo c

O

n -i ^ -t ^-(^ -i ^ n cn o) co oo 1 <o-1 oi-1 oo oo ~-1 · ~-1 σι ~~ i oo o «ooo one rv> one cn oi tn j ^ r i h ^. ~ j cji co n j5k Or cri c — ^ oo o — ^ oon ri h ~-i-~ j to i o o¾ co o i Oi oo j ^ rsa i- 1 — j ^ onc cn co — ^ cD O cn — ^ oo — 'ΐ »^. —' ~~ I (o to en (oo -t ^ cn-1-1 — 'o oi ocoj ^ cn rvj ~-i cn cji -— J co oo ~ J ^. ts3 «3 <3> oi Cft cn — 'O oj r co-1 05 c» — ¹ cnn oo ~ «I υη r oo n-1 r > en en cn ~-1 r ~> I cn to — '~~ i rsa oci ^ rsa oo —' O — Ns cn oo co eo rsa r rva oj tri i o OO ^ OO 1 — 'C <3> — 'Jl -Pk CO —' J ^ Oi -l ^ ~>-σ> (O hh ^ ·

 1 <θ σ> Ν ΓΝ 3 ~-Ι Οΐ Ο 0 00 1 4 ^ 0 iva to 1 rsa tn-1 o -P ^ o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

O CX5 r tO OO OCI \ 3 tn C ri OO *. C ~-1-1 OC »ΟΊ O OO C3¾-1 4 ^ — ^L CC 4 ^ 00 3 <0 00 00 CO — 'IN3 OO N3 O <3> --- 1 OOC Oi I OO-I tO OO O OJ ^ -JO Isa -J OS OS C — ^ O -I ^ C — 'CJ1 C 1 CO CO

o o z o z o z z z o o o z o z

Debate

瞧 0 ΖΖ 00 ι δοε ιζ- 696 'εε- z- 881 a Human HO W09 INOIV

0 09 "63 00 ι • εε- ε- 9LL ι- 881 a y

0 Ifr 83 00 ι LLS n- • εε- ε69 ι- 88 L a 330 3C09 INOIV

0 09 Ζ 00 ι 616 9ε- 'εε- z- 881 a y People 300 ■ ■ V

0 39 00 ι π- οε κ-365 • 0- 881 a Human 130 0S09 W01V

0 W 92 00 ι 18ε ss- m ε- οεε 0- 881 a ιαο 6309 INOIV

0 68 LZ 00 ι 9ε- 9ΖΖ • l-881 a y People 90 8209 隱

0 96 LZ 00 ι O 08 LZ- 919 ε-696 0-881 a y People 80 WO 丄 V

0 96 LZ 00 t B εε 8ε- 66 se- 983 ι- 881 a Human V0 誦 W01V

N Z l LZ 00 ι 01 O LZ- no O ε-• 0-881 a y

0 • ιε 00 ι m ■ 9ε--in z- O 81 a Π31 0 W09 ■ V

0 IS 00 ι 086 9ε- 986 O ε- 066 • 0-O 81 a Π3Ί 0 C209 隱

0 98 ΖΖ 00 Ί OLZ 6ε- 98 L 391 Λ 81 a n, ZQO 3309 INOIV

0 SC 00 ι S086ε- ε, 6ε- ε9 卜 卜 a IQO 1309 隱

0 6 O UG 00 ι KO · 6ε- οιε • 0-a nyo, 90 0209 INOiV

0 ε ι οε 00 • ι 939 LZ-68C 6S • 0-Z.81 a ηo, 90 6 【09 WOIV

0 ιε 63 00 ι 169 '9ε- 003 6ε- • 0-81 a Π3Ί V0 誦

N 09 "62 00 ■ ι ZLZ 9ε- C29" 69- 981 • 0-a (Ί ，, 乙 109 109 ■ V

0 80 00 ι 8 π- 9C0 • 6C- 996 1 981 a mo 0 9109 I / UOIV

0 60 "62 00 ι κ-6C- 8 ■ 0 981 a Π, 9 0 9L09 WO 丄 V

0 8ε • 6S 00 'ι LSL oe- 998 9C- afr • 0- 981 a ΠΊ9 230 刚 V

0 80 I 00 ι 9 £ 8-LU Li-εB 6 • 1-981 a ΠΊ9 L30 S109 ■ V

D B 8 8ε 00 ι • οε- m 9ε-868 ■ 0-981 a Π, 9 αο 2109 ■ V

0 ζι '9ε 00 Ί ■ οε- ι ζ' 8ε- Ζ91 ■ 0-981 a Π, 9 90 U09 WO 丄 V

0 68 • εε 00 ι ζζ-8 O I 8ε-O οε • 0 981 a ηΐ9 ao 0L09 W01V

0 6ε ∎οε 00 L S B 6 ζζ- 6ε-1 s • 0 981 a η, 9 ο 6009 ■ V

N S6 "63 00 ι 03ε ιζ- ^ 89 • 1 981 a mo Ν 8009 lAIOlV

0 98 • οε 00 • ι 6 6 ζζ- '-010 1 981 a 1VA 0 009V

0 9 "62 00 • ι ζζ--66 O ■ 1 S81 a 1VA 0 9009 W01V

0 017 ζζ 00 ι LZ6 990 £ 83 "9 981 a ΊΥΛ 390 9009 INOIV

0 98 ιε 00 Ί 9 • εε- ZZ9-6 981 a "IVA 190 W09 隱

0 ΖΖ ιε 00 'ι 2ε- 839 O 10 981 a 1VA 90 8009 W01V

0 ιε 00 'ι 19 • ιε- m-8 B 6 Ζ 981 a 1VA V. Picture

 N S9 'εε 00 • ι οε- 69S Ζ 981 a 1VA Ν 1009 隱

0 9 O π 00 ι m--οει ε m a dSV 0 0009 隱

0 00 ι "63- m Ζ ma dSV 0 6669 INOIV £ 00 / Z.00iai / X3d 6 8 £ 0/800 ΟΛΑ >>>>>>>>>>>>>>>>>>>>>>>>:>>> Ooooooooooooooooooooo oooooooooooo

oooooozoooozoozoooozo ooooozo

Ζ

 "Co _pa« cn "-1

CD CO

ri-J

ri

IIIIIIIIIIIII 1 1 IIIIIIIIIIIIIIIIII 1 II n cn oi nn on ji en ri cn n ri d oi ci cn cri ^ no "> cji oi cn nn J ^ c oi ji cn ai cn oo o oo oo-^ j o¾ a¾ 4 ^ cji oo o> --ja> oi cco <one o o one oo co co one o co ho cn oi -i ^. -c ^ j ^ c — »-co ^ — ij ^ o — '• h — ^ co — ^ oo o oo ooro — J ^ ι — »■ co oo o to o> oo o ^ ooo ^-^ J Co ocrr o¾ o> ^ oo o oo co oo ^ ho oo oc <o cj o> o> ^ ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo oooooooo

O) n ji n on n ai ΟΊ ΟΊ ^ · ^> 4 ^ CC ^ AAAA *! ^ * ^ ^> · ^ ^ ^> Ο ^ ο <-^ J n 3 CD OO OO CO OOI Cn Oi ** JOOC hO 3 — '-o to o oi o-^ jno oo ^. oo to-«c ^"-1 co c oo --- i ¾ »h one o one h one oi one cc oi A cn r ai ro ai j ^ co σ> cn-»i cr> on J ^ noo ichiichi i ro oo> rsD j ^. cji ji o — ^ -P ^ o ro rnor oo o ho — ^

o o z o zr o o z o z o o o z o z o z

ATOM CO

O

 o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o r c c c c c c c ^ A A A J ^ ^ ^ ^!

 o — ^ en an ro ^. co i co o oo ^ j co oo-«-j -p ^ on a¾ ni oo co O" ^ J O¾ ai no> 一一 c ho n co co co ^ i ro o> oo ai — ^ ocorc oi — »-o> co —»-o¾ cn ^ O fs3 --- 1 oo ro oo oo on ic one ^ J or cn o O "^ to oi" »J ho one oo n oi oo cn h ^ j oo ^ ι 4 ^ 1 oo — »■ JI r co σ¾

ozooozooozozzzo

o o o o o o o o o o o o o o o o

o

o

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 σ> σ¾ 4 ^ CO Coincident oo ro ro CO CO O <yσ> Jl σ> an Ol CJl CO CO CO ro ro OO oo O one oo

 o ro CO ro CO cn o CO o CO ro ro oo 1 CO CO oo ro ro οο r CO oo σ¾ CO cn o σ> CO ro o o o to CJl oo o Jl o o

Ο οο-»j --- 1 <o oo σ σ¾ ro ho <oo CO 1 o cn r o oo o

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I i 1 1 O CO CO CO CO CO CO CO CO O O O CO CO CO CO CO CO 4 ^

 ο O CO CO CO o CO CO «-j oo Jl cn € J> oo oo oo O o o o O o o CO C CJl Jl CO

CO ^ CO <o oo CO o 1 n -J CJl oo O N3 O O σ> ro r> o CO ho CO OO oo ro oo <O CJl o oo an σ> <o CO CO o cn CO σ

 ο σ> C o o σ¾ CO o cn σ¾ o CO O CO ^ r O cn cn ^ o> O o ro Jl o

1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 cn ι cn cn cn CJl Jl n Jl cn Jl CJl n Jl Jl n Jl ai cn CJl Ol on an cn cn nn cn cn on cn οο οο σ¾ -J n σ> σ> ΟΊ o¾ CJl CO o CO CO O CO cn CO CO h CO σ¾ cn CJl CO

CO O ho CO O CO oo O cn o σ> o cn oo CO ro ro ro σ> oo O CO o OO σ> ^ oo o C ""-«1 ho σ> o 7> oo o C n oo ^ 1 CO oo ro ro Jl h 7> O cn • ^ j O CJ> n ro σ o cn h CO o io oo 1 σ¾-«jo ^ ay ο oooooooooooooo O o ο ooooooooooooo O oooo ο ooooooo O ooooooooooooooooooooo o O oooo O CO CO CO O CO CO r CO ro h ro CO CO CO CO CO CO O h ro O ho CO ro CO O CO CO CO CO

CO o C ro 3 ro o CO o CO OO OO ooo oo ^ 1 <o CO CO CO C oo oo oo Jl OO σ¾ σ¾ o ro o oo σ¾ cn oo h oo oo CO cn σ¾ ho o O σ> o C o cn o cn o O oo CO O o

o o z o o z o o o z o z o z o z

ND 203 ο ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο

 σ O O 6210 CD 3> N m C7 C5 OT> ϋ σ C¾ CD 3 5 CD> O one h ho one r

― '11' 11 '' '' '' ''>>>>>>> C5 CT> i> Cr>>>>>>>> '' '' 29 '60' <■ <Be "" ~ ~ <~ <OOGOGOOG "" "" "" "" "OCO oooooooo

oo oo o <o co co oo oo rc ^ n o¾ oo oo ooor — »· ο ο ο — ^ oo oo oo" "--1 αι σ> σ¾ ι σ¾ οο σ> οο i ^ c ji ru 6204i co oo cn o ** J CJ> o ji h O h o¾ h — »-σ¾ Γ« "-1 1 ΟΟ ΟΟ Γ 1 JI O¾« -j ^ --j ^ n 4¾ oo cri o> o> o> ho o> ai o o¾ ^ o> c oo o¾ oo o oo oo D ^ J OO ¾ o oo ^ --- 1 ccccccccccccccccccccccc cccccc ^ i ^ one r one one roonj ^ co A co j ^ to oo oo oi ai oi cn o> ι σ> σ> σ> σ¾-^ ι

»-O co -p ^ -p *. O — *-ho ji co 6202 ^ r-^ o> o> — ^ oo on D to --- ι ο <ο — *-* -J n oo co oc CT> ooo> cn n -p ^ — »-ho ^ —»-o-*-J-^. Oo oo — »-^ ^ ^ ^ J OO" "--1 —» ■ to cic ho r os to i ^ · ji co co ^> cco) io co ^ ic — j- <o -t ^ oi ^ ro -pfc. o oo ^> roo — ^ «ι coo

 J1 1 3 ^ cn 1 σ> co co oo oo --- 1 6200 ι --- 1 oo --J co oo oo cxs i o n cn -i ^ c 4 ^ -t ^ o ^ ^. A) 0) 0o

— ^ RvD o) ^ ro --- i cji o ^ rs3 cn rs3 Ji co>-^-^ oo nn co oo-* j-^ roo — »-o ^ ι — * oo --- 1 σ> oo σ> — ^ ji o --- 1 one oo «t ^ o¾ oo o> occoh ^ oo oo one r oo o oo oo on ^ 1 co oo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooo

I «■> I <n co on oo --- i-^ c ^. ^ Oo ^ co oo cri oco 4 ^ ri ooro oo co ^. — ^ O — ^ c ^. Co c ^ o¾ ji ^ N3 Co 0 ^ o rN3 C oo cji r co oo <o — ^ --- 1 co ""--I OO C ^ ** J OO — »· — ^ ho OZ! OZOZOOOZOZOZO

o o o o o o o

 ro

 -<-Ye ye ye ye ye ye ye ye ye-<

1 o

s s s s s s ≡ ≡ ≡ ≡ ≡ s s s s s s s s ≡

> ■ σ σ-^ i c x x x x x x x x x

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

1 1 1 1

 One

One - - - - - - - - one hundred eleven "A '-' eleven o ^- eleven

 1 ^ rNO C c o 1 ^> ^ 1 — 1 ^ 1 o ο o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o i i i

-σ ο ο ο ο -σ ο ζ ζ ο ζ ο ο ο ζ ο ζ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο

一 一 一

One one one

 o o o ■ o σ¾ 丄

 σ¾

 o cn σ> o

 !

 σ>-^. σ¾ o o o o o

 o σ> σ¾ oo

 o o ro o Ο o o o o o o o o o o o o o O o o O o o o o o O o o o o o o o o o o o ο o o o o o o o o o o o o o o o o o o o o o O o o o o o o o o o o o σ¾

o o o σ o o o o o o o o o o o o o o o o o

AM S GTP 002TO 6287B ■ ■ ■>■>■>·>·>·> · 3>-3>

ο ο ο ο -σ σ ο ο -α ο ο ο ο -ο ο ζ ζ ζ ο ο ο ζ ζ ο ο ο ο ο ο ο ο ο

 »C is3 — ^ oo co co i — ^. C h h — 'cn cn cn h isa c co en on r —' — <— — —

^

^ m o XXXXXXXXXXXXXXXXXXXXX

^

^ mo

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

 »~ L oo oo oo oo c rss c c rNs c c c

— — Ooo -oooo -ooooo -o 2: 2: oz: ooozz: sooooooo

r r ho I o I h I I I I I

rr ho I o I h IIIII

 ro o o o

oc oo oc oo c — ^ c ^ joroo -P * .r co-^. n oo r ai rs3 C c o¾ o¾ ^ cy> oo o ^ ooiooo co oo cT oo oo r co oi o ji ^ c ^ ^. — ^ «-Jhc cn cj r o¾ oo c oo« l oo — ^ — ^ rr> n o¾ ≥ *. N <on O> --J OI O * -J --J 4 ^ OO JI OO oo oo oo

--- 1"^ co hrc co oon

--- 1

I ll IIIIIIIII t IIIIIIIIIIIIIIII r an — ^ — ^ en h — »■ ncc ai cji an an cji ji ji ji ji an on cji cji ji n ji n ai ooo o¾-^ cco co — ^ σ¾ σ> αι σ> ο οο co c ro hoh ι o oo σ¾ oo σ> οο roco> o> o> ai-»jc o¾ ^ ∞ o) Ο ・ ^ ΟΊ ΟΟ o> <oc _ ^ cca) --- 1 ro oo oo« i ^ co — »-oo <ohn — ^ σ ^ ι o σ> J ^ ^ -J oo ^ j co n oo ronc --- 1 co co oo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooo oo 4 ^ ^ o> rr oo r — ^ r xi co ^ j ji c <on σ n ^ -J n en «I OO OCJ> C CT TI ^ no" ^ oi c oo co oo ro no cn co ^ jooo> oo o oo cri o 7i <or- -1 n rs ^ σ> oi oo ^ jc OO AO -J OO ^^ OO OO CO o oo--J co h ho o> ho c oo ir cn ¾>

o o o o o o o o o o o o o o o o o z z o z o o o z o z o o o o o o o

GTP ATOM 6359 C4 004 * ο ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ew ee ee eeェ 工 工 工 工 工 ο ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο οοοο ο ο ο ο ο ο ο ο ο

I I I I I I I I I I I I I I 1 I I I I I 1 C C 1 I 1 C TI OI I I- I C C 1 1 C ^ CO I 1 I

^ 00 Cr> C 4 ^ U3 CO OO (0 OOOC CO-IOOOO — 'CJ1 CO J1-1-I CO OO Oi —' Ο Οϊ 4 ^. Cn en ο σ> σ> rsa ^-- en c σ>-1 to iva oo N3-1 lo ^ cn cn oo o -l ^ o-ro 3 to cn-1

O A O C One-J tO O C One Oi O O OO OI OO One C OO C One-OO — '-CO-OO CO O-t One Γ CO I CO One I One r r One rss

 O <> σ> 3 c co-1 o

co — 'Oi ^ c rsa oo cj ^ cn rva co io —' Co oo — ^ cor-^ j ~~ ι * o -P ^ σ>-σ> one "^ one co co ^ cn oc cn cn jo rss oj io j ^ j! k cn o — '―' -P ^ n ho cn a ^ oo it oo ono co c oo σι co rsj co rss o-^ oo — 'ccncj ^ iva- ■ ι e> ■ ~> ι r cn oo

I I I I I I I I I I I I I I I I I I I I I I I I I I I

 C rsa co co co — »i r 4 ^ ¾> c i r co ~~ ^ s>. Oi r«> c * j — ^ co io oo ~~ ι rsa- 1 — '~-1 co cn oo ~~ ι οο —' C o5 to j5k O o ~ J cn oi ~-1-1

1 o «oo — ¹ ~-1 1 ^ ~~ lo cn oo j ^ oi o oo cn cn — 'Co — ^ cn ~-1 cn c¾ os co cn-1 co co-1 <ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooo .osco ho hc 4 ^ ri 4 ^ crccchcrcr • ^ chchcc

 The

 ~ »I ~ ^ i oo oo 4 ^ cn — ^ j ^ co cn oo co cn ~» ι rss no-ι οο One-1 co ~-i co o One cn cn-1 rss — 'o oo

o o o o o o o o o o o o o o o o o o o o o o o1 203 o o o o o o o o o o o o o

Par 2018 >3>3>3>3>3>>3>3>>

— 1 —1 —1 —i —1 -H —i -H -H —1 — \ —1 —1 —1 —1 —1 —1 —1 —1 —1 —1 —1 —1. 1 —1 —1 —1 —1 —1 —i — 1 oooo ο o O σ OO o O oooooooooooooo OO oooooo O o ≤:

σ> σ> σ> σ¾ σ> σ> σ σ σ> σ¾ σ> σ> σ> y> σ σ>

 4 ^ ^ 4 ^ ^ ^. 4 ^ σ> σ> σ¾ σ¾ n n an C CO

 σ¾ cn ro ο <oo σ> ho oo cn ho CO oo -J σ> cn C ro ο OO ο ο o ο Ο oo O Ο oo ο ο ooo ο ο o oooo O ooo O oooo ee ee e πェ ェ ェ ェ = = = ェ Z ェ ro h h h ro h ro ro ro h ro ro ro ro ro ro ro ro ho hhh ro ro ro ro hh ro ro o o o o o o o o o o o ooooooo o ooooooooooooooo oo oo oo oo oo oo oo oo oo oo-»j --- 1-1 --j σ¾ σ> o> σ> CJ> σ> σ > σ> <3> cn Jl cn JlO oo σ cn O ro o oo σ> Jl O oo CO oo σ Jl CO ro OO CO σ¾ CJl

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 t t

CO ro CO 1 CO OO h CO ro CO CO 1 1 1 CO 1 ro ro oo n cn O o OO σ> oo oo cn CO o second ro CO O ho ro Co cn oo ""--1 ro h CO cn "-« ■ 1 ro ro oo O <o CO o an σ> ro ro »-J Jl CO CO CO σ¾ oo oo

CO cn CO σ¾ O CO n σ σ CO O ho oo n oo Jl cn oh oo CO o cn CO O h --- 1 o oo on O ro CO CO oo oo oo CO 1 h σ> CO cn Jl 4 ^ cn «1 h

 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 1 h 1 O ^ ro ro ro O ro in ro O CO CO aai ai ro ro h C 1 ro ho 1 CO

CO 1 <> ϋΐ o cn σ> oo σ> ho CO CO CO 4 ^ CO oo oo O oo O o to o oo CO oo σ ΟΊ O o O ro oo CO CO CO h CO O CJl h O CO CO O σ >-^ O ro σ> Jl oo ooa σ> --- 1 cn oo <o T1 CO h cn CO oo CO --- 1 n O oo σ> <CO ro σ> ro Oi «-j cn CJl oo oo -^ CO CO σ> σ> CO σ o ^

1 1 1 1 1 1 1 1 1 1 1 1 3 ro CO 1 Jl h 1 cn o oo ro oo ""--1 oo o -J oo σ

cn ro CO CO o cn o o O o ο o O o o o o o o o o o o o o o o o o o O O o o o o o o o o o o o O o ο o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o cn h CO CO CO ro cn CO cn CO CO O ro CO CO ro O CO O ro CO h CO O CO■ "-^ 1 CO σ> ^ σ¾ to cn ro CO o --joo ΟΊ O CO ro Jl oo σ> cn oo σ> CO O Jl

cn ro CO CO o cn oo O oο o O ooooooooooooooooo OO ooooooooooo o o ooooooooooooooooooooooo ooooooooooo cn h CO CO CO ro cn CO cn CO CO O ro CO CO ro O CO O ro CO h CO O CO

CO oo o ro ro CO oo h ro O ^ 1 σ¾ oo CO CO h O σ> o h C ai oo no o O σ> o σ> σ> ro cn oo o CO 1 CO ro oo σ¾ ro cn CO

CO CO CO CO cn O ro oo cn CO o CO ""--1 CO ho o C

ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ

602 w 00 I 06ε 12- m-0 O 0 "89- H0H 0 /.099 wo 丄 V

10 00 l '61-'6 G Sfr 9S- z ■ 0 9099 ■ V zz 83 00 l 399 • ε-989 9ε-9 • 8 mz H0H 0 9099 ■ V

H0H 0 漏 woiv8ί ■ 9fr 00 • I nz ζ- m "6c- 6S3 09-

H0H 0 leakage woiv

P0 69 00 • I 920 • 9 109 Sfr- 0 ½½ \ ι \ ι H0H 0 3099 W01V

L9 6S 00 l 091 '9 m6ε- m 9- 0313 H0H 0 66 mioiv zo 00 l 98ε • 8 969 19- ζιζ 39-6 U2 H0H 0 86W W01V

00 l 91 919 8S- 609 εε- 8113 H0H 0 O 6W W01V a 00 l IZZ ζ ι m · 9ε- z ιε- L \ \ Z H0H 0 96 ^ 9 W01V

39 00 • I zzo • 91 189 “82-zz-9113 H0H 0 96 ^ 9 W01V

8S end s 00I 8ε end L I 199 ZZ- 8ε- 9 U3 H0H 0 9V

98 K 00 l zzo "9 838, 9S- 66 B LZ- z H0H 0 隱

80 "9C 00 l I 689 LZ- 9Z- H0H 0 26fr9 ■ V ιε" 68 00 I 096 01 on · ιε- IZZ 9ε- ι \ \ ι H0H 0 16W ■ V

8 "68 00 l 908 OLZ 2Z- SOS 0 to \\\ ι H0H 0 06fr9 ■ V

9 • 9S 00 • I S 6 • 01 0 ζι- 899 n- 0U3 H0H 0 隱

90 "69 00 • I • 9 11- B OS 1 G 6013 H0H 0 Lm WO 丄 V

90 00 I 06δ 6- 690 8013 H0H 0 98 麵

19 00 l m L Ofr9 8-908 '8ε- thigh H0H 0 98 ^ 9 隱

10 00 ■ I 9S9 ■ 8 80 '— 916 ■ ε G 9013 H0H 0 Simplified W01V

30 00 • I ■ S I I · ει- 06Z ■ 6ε- 9013 H0H 0 WOIV

16 00 • I m • 6 L99 U- 69C end ε- mz H0H 0 zm 隱 ιζ end S 00 ■ I 6ε end u L61 SI--z H0H 0 WOIV

00 • I B 6fr ■ 6 830 ΊΛ-m ■ ge-3013 H0H 0 08 ^ 9 WOIV

69 00 I S36 • 8 ε 6 卜 • ^ G- 1013 H0H 0 6 9 WOIV

'8C 00 l 111 zz 09L il B 8 "6G- 0013 H0H 0 8 9 I / IIOIV

68 00 8fr8 τι rn 6-168 99- 6603 H0H 0 IftlOlV

19 ε 00 • I 0 ^ 8 • 61 εεο 'ζ ι- 018 zz- 8603 H0H 0 ■ V ιε • 61 00 L ■ 81 0L9 "8-96fr • 61- ■ 0 WOIV

09 L9 00 l 0B 8 • 9 311 03-6S I • s G 9603 H0H 0

LZ 00 ■ I G9 £ 6L-6 £ 6 • ε G 9602 H0H 0 z WOIV

01 '8ε 00 I B 00 ΛΖ- Ρ30 ΖΖ- Slfr n- ^ 603 H0H 0 zm WOIV

 99 00 I 308 03- 618 02- 909 61 8603 H0H 0 im 隱

Li 00 I 9 ΐε η- 90B6ε-969 ΌΙ 3603 H0H 0 om WOIV

C9 00 I 990 9Ζ- 089 ΖΖ- III 9ε- 隱 H0H 0 e I / IIOIV

99 '9fr 00 I 9 9 • 8— L 09- ZL ζζ-0602 ■ 0 2m WOIV d 6 8 £ 0 / 800Z OAV 3>3>3>3>>-->----->-3> 3

 —1 —j —1 —1 —1 —1 —1 —1 —1 —1 —1 →> 5> ■

— 1 —i —1 —1 —1 —i -H -H —1 —1 —1 —1 — t —1 —i —i —1 — (-H -H o ο ooooo OOO ooooooooooooooooo O oooooo OO s:

σ> σ> σ> σ> σ> <> σ> <y> σ> σ> σ> σ> σ> σ¾ <y> σ> σ¾ OS <> σ¾ σ¾ αι n on Jl CJl Jl cn cn cn cn ΟΊ cn cn cn αι CJl CJl nnn cn Jl CJl CJl n CJl cn cn cn cn

 ^ CO CO OO CO CO O CO CO CO ro rh ro r ro h ro ro ho οο σ¾ C oo ^ 1 σ on ^ C ro CO oo on CO ro o CO oo cn CO ro o oo ο ο o ο ooo O ooo OO oooooo ο o O oo O ooooooooooo ェ c = c c c 工 工 o o o ο ο ο oo ο ο ο ο ο ο ο ο ο ο ο σ σ ο ο ο ooooooo oπ ee ee ee ee ee eeェ o o ho h ro ro h ho h ro ΓΝ3 ro h ro ho ro ro ro ro 3 ro h ro ho h ro hr σ> σ¾ cn CJl CJl cn cn cn cn cn cn ^ ^ CO CO CO CO CO CO CO O O CO CO h ro ro r ο CO oo cn ^ CO ro CO OO cn Co O oo-»j σ¾ n O h O oo --- 1 cn

1 1 1 1 1 1 1 1 1 1 1 1 1

 1 1 O CO CO O cn cn CJl cn cn cn

CO οο ro CO o-^ 1 -P ^ CO CO no o J> CO σ> oo -J oo

 r o o oo σ¾ σ O

-1 O CO on Jl oo O cn CO oo ho <o ^ cn> o oo o> σ> o oo oo oo 1 cn o ho O σ¾ cn CO o oo o OO oo oo CD n cn oo CO oh CO Jl CO ho σ¾ cn O ο oo σ¾ O cn oo n σ> OO ona oo ""--1 ro CO O cn --- 1 CO --- 1 CO cn oo oo σ¾

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ho 1 1 1 1 1 1 1 1 ro Jl Ol CO ai cn

-J oo οο -J o One CO o One hoohoo cn cn O OO 1 ^ ho oo o ο σ> o CO Jl CO CO O --- 1 cn 4 ^ OO ""--1 o-^. OS CO oo σ¾ O oo CO

CO CO σ> O oo o¾ CO CD CO cn CO cn oo oo no CO oo O σ> σ> ho Jl cn CO oo CO CO O ro σ> CO CO ro o CO CO CO ai o Jl oo-»jn ro CO oo O

1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1

CO CO CO ro O ro ro h ro h ro CO ro h 1 1 ro ro ο CO O o σ> CO r 4 ^ O oo O o CO O o CO O oo oo CO σ> oo ^ -J σ> σ> oo σ> CO h ro o O oo O cn CO oo O cn oo * -J CO oo oo cn -J rn CO a> ■ 1 oo oo σ> oo oo o oo o O 3 <> Jl CO ο o σ n 1 <o CO CO hho cn o CO Jl ΟΊ --j ^ cn ο o O o Ο ooooooo O ooooooooooooo O ooo O oo ο ooo ο ooooooooooooooooooooooooooooooooo

CJ1 O CO CO ΟΊ O CO cn CO CO O on CO CO cn σ n

CO o oo CO σ¾ C CO oo O on • ^ j cn O oo CJl ho oo ^ 1 o anO oo ro CO O cn O o "" • JOO CO CO CO CO CO C oo -JO o σ> CO C CO CO ^ ro cn ^ CO o ^ 1 oo CO ro 05 CD oo o CO o rs3

ο ο σ ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ σ ο ο ο ο ο ο ο ο ο ο

ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο ο ο σ

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o ee ee ee o o ee o ee o ee o ee o ee o ee o

I 79 65 I I One o

 o oo o¾ o one 78 65

One-one

 I I I I I I I I 6775 I f I I I I I I I I I I I I I

 1 1 1 1 1

 6575

 > o — one

6574 one o o o

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I

 1 1 1 6572 1 1

 One

 O o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o 6569 o o o o o o o o o o o o o o o o o o

ο ο ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο σ ο ο ο ο ο 4 656 ο ο ο ο ο σ ο ο ο ο σ ο ο σ

6550 3>>> ■ 3 »3» »» 3 »3» 3 »■ ooooooooooooooooooooo ooooooooooooooo ≡ so mechanic o

One Ji

 I I I I I I I I I I I I I I I I I I I I I I I I I I I 1 I I I I I I I

 One one ro one hhrh one n oi ccrrr co crnj ^ c cn oo c ~ ^-»J Γ ο σ> σ¾ οο ^^ οο one o¾ o> σ> σ¾ one c cji oo oo o oi oo one crhc — ^- i ^ — ^ o — ^-c oo oo j ^ ro oo o co o "-"-l oo h oo cn ooo> o oo co o> --- o cn cn ni ^ jrcn oo oo oi O -i ^ o 1 oo 1 co 1 ∞ 1 σ> σ> ο¾ ο σ> ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ^> cn> ^> ^> ^ 7 ^ cc 4 ^ co n ^ n cn AC c A Ji cji nh A o> co ^ — »-oo cri oo — ^ o oo oo c" "-« loroo oi oo ji ro ^ jnr — ^ j ^ cn cn • ^ co i O ho noor σ¾ 1 1 0> 00 <0 00 4 ^ 0> 1 oo-»j o¾ o¾ ^ j cn ai ai 1

ο ο ο ο σ ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ σ ο ο ο ο ο ο ο ο

6589 3 »3> 3» 3 »■> ■ ■>■>·>■>■>■>■>>> ooooooooooooooooooooo ooooooooooooooo or ooooooooooooooooooooo ooooooooooooooo IEI 1 3

ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο ο σ ο

IIIIIIII or IIIIIIIIIIIIIIIIIIIII IIIII rr ^ rs3 rs3 0> ac N3 c — 'hhh —' ι r rss ^ c — 'r rsa tsa — ^ rsa rr rsa r 0 4 ^ cn o> ON N3 co rs3 CJi c cri-"- i cn oo c o¾ co cn cc co o oo oo oi oo r rss oo

 Ma-1 n oo --- 1 Ma I I I

oo rs5 o ο · oi-1 cji r oo oj n 1 3 c

oo rs5 o

 I I I I

— ¹ — '—' i \ 3 III iccrc N3 h

 A co o) <

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o oj oo to ho cri h oi ji oi oj r j^ ho ^ -- 1 o n cn oo c -- 1 u oo o -- 1 co co oo m o> co -- i oo c cn r>o c cn <3> n o oi 4i. Oi Oo o o — ' C -- 1 ^ cn to -- i c o c n h n co cn ^ oo -^.

ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooo oj oo to ho cri h oi ji oi oj rj ^ ho ^-1 on cn oo c-1 u oo o-1 co co oo mo> co-i oo c cn r> oc cn <3> no oi 4i. Oi Oo oo — 'C-1 ^ cn to-icocnhn co cn ^ oo-^.

o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

Ma ooooooooooo

一 一 一 一 一 一 一 一 一 一 一 一Yeahee Yeah 3: 3 Yeahee ooooooooooo

1 1 1 1 1 1 1 1 1 1 1 1

 n r oo cn cn co — ^ σ> ο οι — ^ O-^ co c ""-»ι co n oi —»-co — ^-^ ^ c ""-^ ι

^. co a> co — ^ h cD --- o ι οο απ ο ο — ^t oo cn cr cy> cn — *-cn cri — »■ ^ ι is cn σ Ts3 hj ^ ^ jo o¾ one o> nr oo one ccrn oo ro oi o-«iic co o¾ nno <oo> --- 1 1 1 1 1 1

一

one

 CT> COO CT r> ro rrc ^ ccc co co or co ro ro ι 一一 ι — »■ —»-r — ^ rva h — ^ c ^ o ¾ »c ^». — ^ Ro ri 05 oo ri O h — »-o> o> o¾ o oo rino oo o one oo

¾ σ o — * ■ "-一一 一 co h --- ic oo c oo c cn oooo — ⁱ -on cj> c7 c — ^ n oo ^ oo nnr o¾ 1 co on oo ¾ CT o> ji oo oo ro o ^ hc oo c ji oiooo <o> -j ^ jo-^ joooooooooooooooooooo ooooooooooooooooooooo ooooooooooooooooooooo ooooooooooi oo an ^ oo | ^ ^ a> ^ oo ^-^ o¾ ri oo — ^ ji c ^ j ^ -jji ^ oo 1

 O J1 00 0> ^ J ^ J 00 O l-* J O OO O¾ — »-C C P OO OO CO --- 1 O ^ I O O> 0 0¾ CT> C0 05 T1 0 00

o o o o o o o o o o o o o o o o o o o o o o o 2283 6684 o o o o o o o o o o o o o

7 2275 瞧 665

2270 6665 ATOM 6711 0 HOH 2306 -20. 028 0. 232 -12. 075 1. 00 45. 17 0

ATOM 6712 0 HOH 2307 -21. 571 2. 728 -6. 134 1. 00 47. 84 0

ATOM 6713 0 HOH 2308 -22. 942 2. 359-10. 535 1. 00 52. 59 0

ATOM 6714 0 HOH 2309 -27. 389 3. 551-11. 961 1. 00 59. 80 0

ATOM 6715 0 HOH 2310 -26. 992 5. 366-14. 883 1. 00 39. 64 0

ATOM 6716 0 HOH 231 1 -16. 103 -3. 148 1. 00 57. 89 0

ATOM 6717 0 HOH 2312 -20. 903-6. 427 -22. 230 1. 00 42. 20 0

ATOM 6719 0 HOH 2313 -13. 734 0. 908-9. 623 1. 00 54. 57 0

ATOM 6720 0 HOH 2314 -8. 513 -5. 999-8. 232 1. 00 50. 35 0

ATOM 6721 0 HOH 2315 -9. 941 -7. 450 -16. 220 1. 00 38. 78 0

ATOM 6722 0 HOH 2316 -3. 578 -10. 400 -9. 914 1, 00 47. 52 0

ATOM 6723 0 HOH 2317 -21.301 -50. 5 σ> 93 -16. 386 1. 00 53. 71 0

ATOM 6724 0 HOH 2318 -25. 499 -44. 603 One 1. 138 1. 00 55. 18 0

END o

[0 0 9 2]

Example 4

a) Creation of complex model

Using the crystal structure analysis results obtained in Example 3, CMP was fitted to the UMP binding site of Escherichia coli iUPRTase on computer graphics to construct a complex model showing the binding mode. Using docking program Glide on Maestro (manufactured by Schr6dinger), Escherichia coli UPRTase is docked with UMP. After selecting the conformation of UMP with a known interaction mode, amino acid residues within 8A from UMP are selected. MMGBSA (Molecular Mechanics-Generalized Born Surface Area) g was calculated, and a binding mode model of Escherichia coli iUPRTase and UMP was constructed. Next, UMP was replaced with CMP as it was, and MMGBSA calculation was performed for amino acid residues within 8 A of CMP to create a complex model of UPRTase and CMP. This model was used for the subsequent design of mutant enzymes.

We carefully observed this complex model and designed mutations that increase the affinity for cytosine. From this observation, it is effective to replace the glycine at position 205, which has an α carbon atom at 7.3A from the nitrogen atom of the amino group of cytosine, with an amino acid that increases the affinity for the amino group. It was thought that there was. Ε carbon atom exists at position 3.8 位置 from the pyrimidine ring 5 position of cytosine) 1 4 1-position methionine, pyrimidine ring of cytosine 4.3 position from carbon atom 6 position It was considered effective to replace the alanine with a 1/3 carbon atom) with an amino acid that increases the affinity for the pyrimidine ring. Carefully observe the positions of the above three amino acid residues, and select aspartic acid (G205D), leucine (M141L), and valine (A143V) as the substituted amino acids, respectively. A complex model of Escherichia coli UPRTase and CMP having a phenotype was constructed by performing MMGBSA calculations on amino acid residues within 8 A of CMP (Fig. 2).

 [0 0 9 3]

 In the binding model of CMP and mutant UPRTase, the hydrogen atom at the 4-position and the oxygen atom of the backbone carbonyl group of Gly207, the nitrogen atom at the 3-position and the amide hydrogen atom of the backbone of Ala209, the carbonyl at the 2-position Hydrogen bonds are formed between oxygen and the amide hydrogen atom of Gly210.

Asp205 and cytosine, which are the key mutations in cytosine recognition, are bound by an electrostatic interaction between the hydrogen atom of the 4-position amino group and the oxygen atom of the side chain carboxylic acid of Asp. Thus, Asp205 can interact with glutamic acid with the same negative charge. The pyrimidine ring of CMP is bonded to the methyl group of Leul41 by CH / π interaction. In order to bond CMP with CH / π interaction, Lele41 may be Ile or Val having a methyl group. Furthermore, in the vicinity of hydrogen at the 5th and 6th positions of CMP, it is thought that it is bound to Vall43 by hydrophobic interaction. There are few voids at this site, and Leu and lie, which are bulky amino acids than Val, have the potential for steric hindrance.

 [0 0 9 4]

Further, from the complex structure analysis of wild-type UPRTase and CMP, Tyr201, by making a hydrogen bond and As _P 208, a pyrimidine ring sandwiched with Metl41, forms part of a cytosine binding site. This site may be Lys or Arg, which can interact with Asp208.

 [0 0 9 5]

In addition, Argll2, which is known to interact with the phosphate group of PRPP, from the structural analysis of other types of UPRTases, is a very exercise between B5 (5th beta strand) and B6 (6th beta strand). It is in a flexible loop (EMB0 J. (1998) 17: 3219-3232). Limiting the flexibility of the flexible loop may increase the affinity between Argll2 and the substrate. Specifically, if Prol21 on B6 is replaced with a hydrophobic amino acid such as Leu, lie, and Val, which is more bulky than Pro, the hydrophobic bond with Leul54 or Alal50 on A5 (5th α-helix) near B6 It is expected to strengthen. In addition, if Prol21 is replaced with an aromatic amino acid such as Phe, Tyr, Trp, or His, the affinity between Β6 and Α5 is expected to increase due to ΟΐΖπ interaction.

[0 0 9 6]

b) Creation of tetramer model Based on the structural information of the X-ray crystal structure analysis, a tetramer model including the boundary between each monomer was created with graphics using Insight97 (Fig. 3). The structure on the graphics was closely observed, and mutations that increase the affinity between the monomers were designed. Arg36. Located at the tetramer interface (within 5 A from any atom of the adjacent UPRT ase monomer) is distant from Arg36 'from the other dimer. It seems that electrostatic repulsion is occurring nearby. Therefore, if this amino acid is substituted with an amino acid having no charge and no steric hindrance, such as Cys, Ser, Thr, Met, Leu, lie, Val, etc., this repulsion is eliminated. In addition, stabilization of the tetrameric structure can be expected. Similarly, it is considered that electrostatic repulsion occurs in As _P 94 for the same reason, and these are replaced by Gly, Ser, Thr, Ala, Leu, Val, lie ゝ Tyr, Phe, Trp, etc. without charge. This will stabilize the tetramer structure. In addition to eliminating electrostatic repulsion in the tetramer, a similar improvement in activity can be expected by actively strengthening the interaction between tetramers. For example, if Ser46 is further substituted with a longer chain amino acid, such as Asn, a hydrogen bond is formed with E98 'of the other monomer forming the dimer, which may lead to improved CPRTase activity. .

In addition, the 3 arms that extend toward the other monomer are thought to be structurally important. Among them, mutations in the amino acid near Tr _P 66 may lead to improved CPRTase activity.

 [0 0 9 7]

Example 5

Acquisition and evaluation of mutant enzymes (Part 1)

 Consists of the nucleotide sequence represented by SEQ ID NO: 16 for the purpose of substituting the first methionine residue of the UPRT ase of Escherichia coli consisting of the amino acid sequence represented by SEQ ID NO: 15 with another amino acid. Based on the DNA encoding the Escherichia coli UPRTase, a DNA in which the region encoding the methionine residue consisting of the base sequence represented by SEQ ID NO: 17 is substituted with an arbitrary base (nnn), and the base sequence A complementary DNA comprising the nucleotide sequence represented by SEQ ID NO: 18 was synthesized.

[0 0 9 8]

 In addition, for the purpose of substituting the 21st tyrosine residue with another amino acid, as described above, a DNA comprising the base sequence represented by SEQ ID NO: 19 in which the region is replaced with an arbitrary base And a DNA comprising the base sequence represented by SEQ ID NO: 20 complementary to the base sequence was synthesized.

Furthermore, on the plasmid pEUPl, the DNA consisting of the base sequence represented by SEQ ID NO: 21 corresponding to the upstream side of the UPRTase gene and the base sequence represented by SEQ ID NO: 22 corresponding to the reverse strand on the downstream side A DNA consisting of [0099]

 DNA having the base sequence represented by SEQ ID NO: 18 and 21, DNA having the base sequence represented by SEQ ID NO: 17 and 22, DNA having the base sequence represented by SEQ ID NO: 20 and 21, and SEQ ID NO: 19 PCA was performed using Pyrobest DNA polymerase (manufactured by TAKARA BIO INC.), Respectively, using DNA having a base sequence represented by (22) and (22) as a primer set, pEUPl plasmid DNA as a saddle type, respectively. .

 [0100]

 Amplification products of about 0.5 kb, about 0.3 kb, about 0.7 kb, and about 0.1 kb obtained by PCR were subjected to agarose gel electrophoresis, extracted and purified using Qiagen Gel Extraction Kit.

 The obtained amplification products of about 0.5 kb and about 0.3 kb, and amplification products of about 0.7 kb and about 0.1 kb were mixed, respectively, and these two types of mixtures were represented as SEQ ID NOs: 9 and 10, respectively. The DNA having the nucleotide sequence described above was used as a primer set and PCR was performed.

 [0101]

 Since each of the above PCR fragments yielded about 0.8 kb of amplified DNA fragments, the DNA fragments were subjected to agarose gel electrophoresis, extracted and purified using the Qiagen Gel Extraction Kit, and each of the DNA fragments Cleaved with I and I and purified in the same manner as above.

 The obtained DNA fragment was ligated with the expression vector pTrc99A, which was also cleaved with EcoRI and BamHI, and Escherichia coli MClOOO AcodAΔcdd ApyrG :: Km strain was transformed using the ligated product.

 [0102]

のアンピシリンを含む M 9最少寒天培地上に レプリカしたところ、 それぞれ 1個のシングルコロニーが得られたので、 14 1番目のァミノ酸残基の置換体を R1株、 201番目のァミノ酸残基の置換体を R2株と命名した。 Each transformant was selected using ampicillin resistance as an index, and the transformant was combined with 50 mg / l cytosine.

When replicated on M9 minimal agar medium containing 1 ampicillin, one single colony was obtained. 14 Substitute the 1st amino acid residue for the R1 strain and the 201st amino acid residue. The replacement was named R2 strain.

When the base sequence of the UPRTase structural gene portion in the plasmid held by R1 and R2 strains was determined by a conventional method, the 141st amino acid residue in mouth Rin and 205th amino acid residue in the R1 strain were asparagine. DNA that encodes the mutant UP RTase (M141L G205D) substituted with an acid. In the R2 strain, the mutant U PRTase (where the 201st amino acid residue is replaced with lysine and the 204th amino acid residue is replaced with leucine) Y201K P204L) was found. [0103]

 Next, DNA encoding the variant UPRTase (M141L, G205D, Y201K, P204L), which has a single substitution mutation of the four amino acid residues found above, corresponds to the amino acid to be substituted in the same manner as above. It was obtained by a PCR method using a primer DNA having a codon. The obtained DNA encoding mutant UPRT ase each bound to pTrc99A, and Escherichia coli MCI 000 AcodA Acdd ApyrG :: Kra strain was transformed with the conjugate.

 [0104]

 When transformants were cultured on M9 minimal agar medium containing 50 mg / l cytosine and 100 / zg / ml ampicillin, only the mutant (G205D) in which the 205th amino acid residue was replaced with aspartic acid was obtained. Grew.

 Next, for the purpose of measuring the CMP-generating activity of the mutant UPRT as in the R1 and R2 strains, a mutant enzyme tagged with a histidine tag was obtained as follows.

 [0105]

 A DNA consisting of the base sequence represented by SEQ ID NO: 23 corresponding to the base sequence of the 5 ′ end region of the UPRTase gene represented by SEQ ID NO: 16, and a DNA consisting of the base sequence represented by SEQ ID NO: 22 PCR was carried out using Pyrobest DNA polymerase, using the plasmid DNA retained by R1, the plasmid DNA retained by the R2 strain, and pEUPl as a primer set.

 [0106]

 The obtained amplified DNA fragments of about 0.8 kb were each subjected to agarose gel electrophoresis, purified using Qiagen Gel Extraction Kit, and cleaved with Sphl and Hindlll.

 The DNA fragment obtained above was ligated to the expression vector PQE82L (Qiagen) cut with the same and i dni, and Escherichia coli DH5 strain was transformed with the ligated product. Transformants were selected using ampicillin resistance as an indicator.

 [0107]

 The three transformants obtained were each cultivated at 30 ° C in LB medium containing 100 / zg / ml ampicillin at 30 ° C, and the resulting culture was treated with lOO / zg / ml ampicillin. 1% inoculated in a Teriffic medium containing 12 g of Batatotryptone, 24 g of yeast extract, 4 ml of chrysalmouth in 1 L of water and adjusted to pH 7.2, and cultured at 30 ° C for 8 hours. IPTG was added to a final concentration of lmraol / 1 and further cultured for 6 hours, and then the culture was centrifuged to obtain bacterial cells.

[0108] The bacterial cells were sonicated to prepare a crude enzyme solution, and each enzyme with a histidine tag was purified using HiTrap Chelating HP Coulumn (manufactured by Philacia). The purified enzyme was added to the reaction solution [50 arm ol / l Tris-HCl (pH 7.5), 5) ol / l potassium phosphate, 5 讓 ol / l magnesium chloride, 5 fractions ol / l cytosine, lmmol / 1 guanosine. 5, -triphosphoric acid, 1.5 mmol / l PRPP], reacted at 31 ° C, and the resulting CMP was quantified by high performance liquid chromatography (HPLC). The protein concentration was measured using Protein Assay Kit (Pharmacia).

 [0109]

 On the other hand, for the UMP production activity, the crude enzyme extract prepared from the enzyme expression strain without the histidine tag (host is Escherichia coli DH5 strain) was used as the reaction solution [50 ramol / l Tris-HCl (pH 7.5), 5 Thigh ol / l monopotassium phosphate, 5ramol / l magnesium chloride, 5ramol / l uracil, lmraol / 1 guanosine 5, monotriphosphate, 1.5 mmol / l PRPP], 31. The reaction was carried out with C, and the produced UMP was quantified by HPLC. The results are shown in Table 2.

 [01 10]

 [Table 2]

 Table 2

 * 1 Activity measurement host; DH5a strain

 * 2 Growth test host; MC1000 AcodA Acdd ApyrG :: Km strain

nt; not measured [0 1 1 1]

 As is clear from Table 2, no CMP-producing activity was detected with the wild-type enzyme, whereas the mutant-type enzymes produced by the R1 and R2 strains (Y201K P204L and M141L G205D) showed clear productive activity. It was.

 In addition, the UMP production activity, which is the original activity, significantly decreased with the increase in CMP production activity, indicating that the substrate specificity conversion from uracil to cytosine occurred.

 [0 1 1 2]

 Comparing the activities of the four single mutants, only the G205D mutant grew in cytosine-added M9 minimal medium, and UMP production activity was significantly reduced. It was thought to play an important role in recognition.

 [0 1 1 3]

Example 6

Acquisition and evaluation of mutant enzymes (Part 2)

 DNA having the base sequence represented by SEQ ID NO: 16 and SEQ ID NO: 23 using the plasmid obtained by ligating the DNA encoding UPRTase having the amino acid substitution mutation of M141L obtained in Example 5 to the vector pTrc99A as a saddle type PCR was carried out using DNA consisting of the nucleotide sequence represented by the above as a primer set, and a plasmid in which DNA encoding UPRTase having M141L amino acid substitution mutation was linked to pQE82L was obtained in the same manner as in Example 5.

 [0 1 1 4]

 Using the obtained plasmid as a saddle type, PCR was performed using a primer DNA having a codon encoding glutamic acid at the codon corresponding to the 205th amino acid residue as in Example 5, and the 141st amino acid residue was leucine. In addition, a DNA fragment encoding a mutant UPRTase (M141L G205E) in which the 205th glycine was replaced with glutamic acid was obtained.

 [0 1 1 5]

 The DNA fragment was cleaved with Sphl and Hindlll and ligated with pQE82 L, and a mutant UPRTase (M141L G205E) in which the 141st amino acid residue was replaced with leucine and the 205th glycine was replaced with glutamic acid was added with a histidine tag. The expressing plasmid was obtained.

The Escherichia _C0 li DH5 ct strain was transformed with the plasmid expressing the mutant UPRTase (M1411 G205E), and transformants were selected with ampicillin resistance as an index. Example 5 using the transformant expressing the mutant UPRTase (M141L G205E) obtained above and the transformant expressing the mutant UPRTase (M141L G205D) obtained in Example 5 According to the same procedure as above, a mutant UPRTase (M141L G205E) and a mutant UPRTase (M141L G205D) each tagged with a histidine tag were purified.

 [Hi 1 1 6]

The purified enzyme reaction solution [5 O mmol / 1 Tris-HCl _{(P H 7 5.),} 1 O mmol / 1 salts of magnesium, 10 mmol / l cytosine, l mmol / 1 guanosine 5, - triphosphate, 3 mmol / 1 PRPP], reacted at 32 ° C, and the resulting CMP was quantified by high performance liquid chromatography (HPLC). The protein concentration was measured using a protein assay kit (Pharmacia). The results are shown in Table 3.

 [0 1 1 7]

 [Table 3] Table 3

 [0 1 1 8]

 As is clear from Table 3, the mutant UPRTase (M141L G205E) in which the 205th amino acid was replaced with glutamic acid was also evident, as was the mutant UPRTase (M141L G205D) in which the 205th amino acid was replaced with aspartic acid. CMP activity was recognized.

[0 1 1 9]

Example 7

Acquisition and evaluation of mutant enzymes (Part 3)

Using the plasmid obtained by ligating the DNA encoding UPRTase having the amino acid substitution mutation of G205D obtained in Example 5 to the vector pTrc99A as a saddle, the DNA having the base sequence represented by SEQ ID NO: 16 and SEQ ID NO: 23 the DNA consisting of the nucleotide sequence PCR was performed using as a primer a set, DNA encoding a UPRTase with Amino acid substitution mutation G205D in the same manner as in example 5 to give the plastics corner de linked to _P QE82L .

Escherichia coli DH5a strain was transformed with a plasmid expressing the mutant UPRTase (G205D), and the transformant was selected using ampicillin resistance as an index. Using the transformant expressing the mutant UPRTase (G205D) obtained above and the transformant expressing the mutant UPRTase (M141L G205D) obtained in Example 5 in the same manner as in Example 5, respectively, histidine was used. The tag-added mutant UPRTase (G205D) and mutant UPRTase (M141L G205D) were purified. The purified enzyme was added to the reaction solution [50 mmol / l Tris-HCl ( _PH 7.5), 1 Omraol / 1 magnesium chloride, 4 mmol / l cytosine, 1 匪 ol / l guanosine 5′-triphosphate, 1.5 mmol / 1 PRPP The resulting CMP was quantified by high performance liquid chromatography (HPLC). The protein concentration was measured using a protein assay kit (Pharmacia). The results are shown in Table 4.

 [0120]

 [Table 4]

Table 4

 [0121]

 As is clear from Table 4, the mutant UPRTase (G205D), which has only the substitution of the 205th amino acid with aspartic acid, also replaced the 141st amino acid with leucine and the 205th amino acid with aspartic acid. Mutant type

Similar to UPRTase (M141L G205D), it was found to have a clear CMP-generating activity.

 [01 22]

Example 8

Acquisition and evaluation of activity-enhancing mutant enzymes

The plasmid DNA retained by the R2 strain obtained in Example 5 is of the saddle type, and the DNA comprising the base sequence represented by SEQ ID NO: 21 and the DNA comprising the base sequence represented by SEQ ID NO: 22 are used as a primer set. , using Recombinant Taq DNA polymerase hydrolase (Takara Bio) were Erapu loan P CR in the presence of 0.3ramol / l M _g Cl _2.

 [0123]

 The obtained amplified DNA fragment of about 0.8 kb was subjected to agarose gel electrophoresis, purified using Qiagen Gel Extraction Kit, and then cleaved with EcoRI and BamHI. The DNA fragment was ligated with an expression vector pTrc99A, which was also cleaved with EcoRI and BamHI, and the resulting conjugate was transformed into Escherichia coli MCI 000 AcodA Acdd Δρ yrG :: Km strain.

 [0124]

Transformants were selected using ampicillin resistance as an indicator, and the resulting transformants were treated with 7rag / 1 5-fluorocytosine or 7 mg / l 2,5,6-triamino 4-hydroxypyrimidine. About 15000 strains were replicated on M9 minimal agar medium containing gin (containing cytosine 50 mg / L and 100 / zg / ml ampicillin), and growth was examined.

 As a result, 2 strains on the plate containing 5-fluorocytosine (named FC35-1 and FC35-2) and 1 strain on the plate containing 2,5,6-triamino-4-hydroxypyrimidine (TA35-1 Formed a colony.

 [0125]

 When plasmid DNA was extracted from FC35_1, FC35-2 and TA35-1 strains and the nucleotide sequence of the UPRTase structural gene was determined, the mutant enzyme gene retained by FC35-1 strain was the 102nd. The amino acid residue is cysteine, the 198th amino acid residue is glycine, the mutated enzyme gene held by the FC35-2 strain is the 94th amino acid residue is tyrosine, and the mutated enzyme gene held by the TA35-1 strain is It encoded an enzyme in which the 36th amino acid residue was replaced with cysteine and the 198th amino acid residue was replaced with glycine.

 [0126]

 In addition, three types of transformants obtained by transforming Escherichia coli DH5oi with the plasmid DNA were cultured in 100A (LB medium containing g / ml ampicillin, and then the crude enzyme was cultured. Extracts were prepared and CMP production activity was measured, and the results are shown in Table 5.

 [01

 [Table 5]

 Table 5

[0128]

As is clear from Table 5, three strains (FC35-1, FC35-2, TA35) obtained using resistance to the cytosine analogs 5-fluorocytosine or 2,5,6-triamino-4-hydroxypyrimidine as an index. -In addition to the substitution mutation (M141L G205D) of the two amino acid residues of the と し た type mutant enzyme, the UP RT ase mutant enzyme produced in 1) has a new one or two amino acid residues. A substitution mutation was found, and the mutant fermentation The CMP-generating activity of the element increased 1.8 to 40 times compared to the mutant-type mutant enzyme strain.

 [0129]

Example 9

Acquisition and evaluation of enzyme with increased activity by site-directed mutagenesis

 A homology model of UP RT a s e derived from Escherichia coli was created by using the program Insight97 with the UP RT a s UMP complex structure (PDB code 1I5E) derived from Bacillus caldolyticus as a saddle type.

 Next, using the molecular force field of the program CHARMM22, we created a UMP conjugate model with minimized energy. Based on this model, a CMP complex model of M141L G205D mutant enzyme was created to minimize energy. In this complex model, voids were found in the vicinity of H5 / H6 of CMP, so that the 143rd alanine residue was filled with bulky hydrophobic amino acids such as palin, leucine, and isoleucine to fill this void. It was expected that bonding with CMP would increase.

 [0130]

 Therefore, for the purpose of replacing the 143rd alanine residue with palin by site-directed mutagenesis, the codon (GCA) that codes for the alanine residue based on the base sequence represented by SEQ ID NO: 16 DNA having a base sequence (base sequence represented by SEQ ID NO: 24) substituted with a codon (GTT) encoding the group, and a complementary sequence complementary to the base sequence (base sequence represented by SEQ ID NO: 25) A DNA consisting of

 [0131]

 Plasmid DNA held by the TA35-1 strain using the DNA consisting of the nucleotide sequences represented by SEQ ID NOs: 25 and 21 and the DNA consisting of the nucleotide sequences represented by SEQ ID NOs: 24 and 22 as primer sets, respectively. PCR was performed using Pyrobe st DNA polymerase.

 The amplified DNA fragment products of about 0.5 kb and about 0.3 kb obtained by the above PCR were purified after electrophoresis on agarose gel.

 [0132]

 Next, a mixture of the two kinds of amplified DNA fragments obtained above was used as a cage, and PCR was carried out using DNA consisting of the nucleotide sequences represented by SEQ ID NOs: 21 and 22 as a primer set.

 The approximately 0.8 kb amplified DNA fragment obtained with the above PCR was purified by agarose gel electrophoresis, and then digested with l.

[0133] The DNA fragment was ligated with the expression vector pTrc99A, which was also cleaved with EcoRI and BamHI, and the resulting ligation product was used to transform Escherichia coli DH5 α strain, and transformants were selected using ampicillin resistance as an indicator. did.

 By extracting plasmid DNA from the transformant and determining the nucleotide sequence of the UPRTase structural gene portion by a conventional method, DNA encoding a mutant enzyme in which the 143rd alanine residue is substituted with valine is obtained. The plasmid DNA was named pA143VTA35-l.

 [0134]

Next, when the transformant was cultured in LB medium containing ampicillin 100μ _§ / ιη1, it was measured CM P generation activity by preparing a crude enzyme extract from the culture, the original T A35-1 strain The specific activity was increased about 2.5 times compared to the mutant enzyme produced by.

 [0135]

Example 10

Acquisition and evaluation of activity-enhancing mutant enzymes (Part 2)

 The plasmid DNA retained by the A143 VTA 35-1 strain obtained in Example 9 is of the vertical type, and consists of the DNA consisting of the base sequence represented by SEQ ID NO: 21 and the DNA consisting of the base sequence represented by SEQ ID NO: 22. As a primer set,

Using Recombinant TaqDNA polymerase (manufactured by Takara Bio Inc.), error-prone PCR was performed in the presence of 0.3 mmol / l MgCl 2.

 [0136]

 In the same manner as in Example 8, the obtained amplified DNA fragment of about 0.8 kb was subjected to agarose gel electrophoresis, purified using Qiagen Gel Extraction Kit, and then cleaved with EcoRI and BaraHI.

The DNA fragment was ligated with an expression vector _P Trc99A, which was also cleaved with EcoRI and BamHI, and Escherichia coli MCI 000 AcodA Acdd 厶 pyrG :: Km strain was transformed with the resulting conjugate.

 [0137]

 Transformants were selected using ampicillin resistance as an indicator, and the resulting transformants were obtained from M9 minimal agar medium (cytosine 4 Omg / L) containing 40 mg / 1 5-fluorocytosine or 50 mg / l 5-methylcytosine. 100; containing g / ml ampicillin) About 15,000 strains were replicated on each of the above and examined for growth.

As a result, colonies formed 1 strain (named FC-5) on the plate containing 5-fluorocytosine and 2 strains (named MC-8 and MC-21) on the plate containing 5-methylcytosine. '[0138] When plasmid DNA was extracted from FC-5, MC-8 and MC-21 strains and the base sequence of the UP RTase structural gene was determined, the variant enzyme gene retained by FC-5 strain was 167th. The mutated enzyme gene held by MC-8 is the 46th amino acid residue in asparagine, and the mutated enzyme gene held in the FC-5 strain is 121th amino acid residue. Enzymes substituted for isoleucine were encoded.

 [0139]

In addition, three transformants obtained by transforming Escherichia coli DH5α with the plasmid DNA were cultured in LB medium containing 100 / g / ml ampicillin, and then crude enzyme was extracted from the culture. The solution was prepared and the CMP production activity was measured. The results are shown in Table 6.

[0140]

 [Table 6]

Table 6

 [0141]

 As is apparent from Table 6, UP RT a produced by 3 strains (FC-5, MC-8 and MC-21) obtained using resistance to the cytosine analogs 5-fluorocytosine or 5-methylcytosine as an index. In addition to the 4 amino acid residue substitution mutations (M141, G205D, R36C, E198G) of the mutated type enzyme, the se mutation enzyme has a new substitution mutation of one amino acid residue. As a result, the CMP production activity of the mutant enzyme increased from 1.3 to 2.3 times that of the mutant enzyme-expressing strain.

 [0142]

Example 1 1

Production of CMP-producing bacteria using corynebacterium / ammoniagenes as the host Corynebacterium ammoniagenes has a high ability to supply PR PP and is abundant in industrialization when synthesizing salvage from bases to nucleotides. Suitable as a reaction host. Therefore, a plasmid that expresses the UP RTase mutant enzyme was constructed as follows in Corynebacterium ammonigenes.

 [0143]

 Perform PCR using the plasmid PA143VTA35-1 obtained in Example 9 as a mirror and using the DNA consisting of the base sequence represented by SEQ ID NO: 26 and the DNA consisting of the base sequence represented by SEQ ID NO: 13 as the primer set. It was.

 The obtained amplified DNA fragment of about 0.7 kb was purified by agarose gel electrophoresis, purified using Qiagen Ge 1 Extraction Kit, and cleaved with BamHI.

 [0144]

In addition, a DNA fragment having the nucleotide sequence represented by SEQ ID NO: 27 containing the promoter sequence _P 54-6 (GenBank AJ132582) expressed in a coryneform bacterium, is added to the plasmid vector PCS299P (Japanese Patent Application No. 11-110437: W000 / The expression vector PRI109 obtained by inserting into the Sse8387I_BaraHI site of (63388) was also cleaved with Sail and BamHI, and The DNA fragment was bound. Escherichia coli DH5 strain was transformed with the resulting conjugate, and transformants were selected using kanamycin resistance as an index.

 [0 1 4 5]

 Plasmid DNA extracted from the resulting transformant, subjected to restriction enzyme digestion analysis and nucleotide sequence analysis, and inserted into a 0.7-kb DNA fragment containing the desired mutant UPRTase gene It was confirmed that a plasmid DNA having a DNA was obtained, and the plasmid DNA was named pRA143VTA35-l.

 Next, plasmid pRA143VTA35-1 was introduced into Corynebacterium ammoniagenes ATCC21170 strain by electroporation (FEMS Microbiology letters, 65, 299 (1989)), and transformants were selected using kanamycin resistance as an index. The transformant was named Corynebacterium ammoniagenes ATCC21170 / pRA143VTA35-1. [0 1 4 6]

Example 1 2

 CM P Production Test (1)

 Example 1 Corynebacterium ammoniagenes ATCC21170 / pRA143VTA35-l strain obtained in 1 was added to seed medium containing 20/1 g / ml kanamycin 1 [glucose 50 g, polypeptone

(Nippon Pharmaceutical Co., Ltd.) 10g, Yeast extract (Nippon Pharmaceutical Co., Ltd.) 10g, Urea 5g, Ammonium sulfate 5g, Lithium dihydrogen phosphate lg, Nitrogen hydrogen phosphate 3g, Magnesium sulfate heptahydrate lg, iron sulfate heptahydrate lOrag, zinc sulfate heptahydrate 10 mg, calcium chloride dihydrate 100 mg, manganese sulfate pentahydrate 20 mg, L-cysteine 20 mg, D-calcium pantothenate 10 mg , Vitamin B ^ mg, nicotinic acid 5mg and piotin 30 / zg in 1L of water, adjusted to pH 7.2) in a large test tube containing 10ml, inoculate one platinum loop, 30 ° C, 24 The culture was shaken back and forth at 300 rpm for a period of time.

 [0 1 4 7]

 Next, 4 ml of the resulting culture was inoculated into a 2 L baffled Erlenmeyer flask containing 250 ml of a liquid medium having the same composition as described above, and subjected to rotary shaking culture at 190 ° C. for 24 hours at 30 ° C.

Seed medium 2 [Glucose 100g, Erlich Katzo extract (manufactured by Kyokuto Pharmaceutical Co., Ltd.) 10g, Polypeptone 10g, Potassium dihydrogen phosphate lg, Bacterium hydrogen phosphate lg, Magnesium sulfate Japanese lg, Iron sulfate heptahydrate 20mg, Zinc sulfate heptahydrate 10mg, Calcium chloride dihydrate 100mg, Manganese sulfate pentahydrate 4. lmg, i3-alanin 15mg, L- Inoculate a 5L fermenter containing 2.25L of Cystein 20mg, Piotin 100μg, urea 2g (separately sterilized) and vitamin 5mg (separately sterilized in 0.9L of water, adjusted to pH 7.2). At 32 ° C, aeration volume 2.5 L / min, 600 rpm, the culture was aerated and stirred while adjusting to pH 6.8 with concentrated aqueous ammonia. [0 1 4 8]

When the glucose in the culture supernatant is consumed, 250 ml of the culture is aseptically collected and the production medium [glucose 150 g, potassium dihydrogen phosphate 10 g, dihydrogen hydrogen phosphate 10 g, magnesium sulfate Japanese 5g, Iron sulfate heptahydrate 20mg, Zinc sulfate heptahydrate 10rag, Calcium chloride dihydrate 100mg, Manganese sulfate pentahydrate 20mg, Copper sulfate 'pentahydrate 5mg, Nicotine acid 5 mg, beta-Aranin 15 mg, glutamic acid lg, L-cysteine 20 mg, Biochin 100 / g, urea 2 g (separately sterilized) and vitamin 5 mg (separately sterilized) comprises water 0.9 L, was adjusted to _P H6.8 Medium] A 5 L fermenter containing 2.25 L was inoculated and cultured with aeration and agitation while adjusting the pH to 6.8 with concentrated ammonia water at 32 ° C, aeration rate of 2.5 L / min, and 600 rpm.

 [0 1 4 9]

When the glucose in the culture supernatant is consumed, 40 ml of the culture is collected and placed in a 250 ml microjar (BMJ-25, manufactured by Able), to which 5.2 g glucose, 300 mg cytosine, and SANISOL B-50120 mg are added. was added, 32 ° C, aeration rate 20 ml / min at 1100 rpm, was carried out CMP production reaction while adjusting the _P H7.6 at 4 mol / l KOH. As a result, 21.5 g / L (58.7 aol / l) of CMP was produced in 24 hours after the start of the reaction. At this time, CD P and C TP by-products were 1.6 olol / l and Omraol / l, respectively, and the conversion rate from the attached cytosine to CMP was about 87%.

 [0 1 5 0]

Example 1 3

 CMP production test (2)

 Inoculate one Escherichia coli DH5a / pA143VTA35-1 strain obtained in Example 9 into a large test tube containing 10 ml of LB medium containing 100 μg / ml ampicillin at 30 ° C for 18 hours. Reciprocal shaking culture was performed at 300 rpm. Next, 3 ml of the resulting culture was inoculated into a 2 L baffled triangular flask containing 300 ml of LB medium containing 100 g / ml ampicillin, and cultured with shaking at 30 ° C for 20 hours at 190 rpm. . After completion of the culture, the culture was centrifuged to obtain bacterial cells.

 [0 1 5 1]

 On the other hand, Corynebacterium ammoniagenes ATCC21170 strain was cultured in a 5 L fermentor in the same manner as in Example 9 under the condition not containing kanamycin. 40 ml of the obtained culture was placed in a 250 ml microjar, and 600 mg (wet weight) of Escherichia coli DH5 ct / pA143VTA35-1 strain obtained above, 4.0 g of glucose, 400 mg of cytosine, and Sanisole B-50120 mg were added to this. With the addition force D, CMP production reaction was carried out while adjusting the pH to 7.6 with 4 mol / l K0H at 32 ° (aeration rate 20 ml / min, 1100 rpm. As a result, 24 hours from the start of the reaction CMP was produced at 14 g / L (40 mmol / l).

[0 1 5 2] Example 1 4

 CTP production test

 (1) CTP production from orotate

 Escherichia coli 294 strains § ccharomvces cerevisiae

50 mg of ampicillin 50 mg of MM294 / pCKG55 strain (JP-A-5-276974, FERM BP-3717) introduced with the plasmid pCKG55 expressing the CTP synthase gene from Choline-phosphate cytid iyltransferase and Choline kinase gene L medium containing tryptone (manufactured by Difco) 10g / L, yeast extract

(Diffcone soil) 5g / L, medium containing 5% sodium chloride 5 ₈ and 11 adjusted to 7.2] Inoculate 2L baffled Erlenmeyer flask with 200ml and rotate at 25 ° C for 24 hours at 220rpm Cultured with shaking. 20 ml of this culture broth, glucose 5 g / L (separately sterilized), peptone (manufactured by Kyokuto Pharmaceutical Co., Ltd.) 5 g / L, disodium hydrogen phosphate 6 g / L, potassium dihydrogen phosphate 3 g / L, ammonium chloride lg / Liquid medium consisting of L, magnesium sulfate heptahydrate 250rag / L (separate sterilization) and vitamin Bl 4mg / L (separate sterilization) 2. Inoculate 5L culture tank containing 5L and, culturing temperature 28 ° C, was performed stirred 600Rpra, culture conditions aeration 2. 5L / min, the culture ¾ while adjusting the _P H7. 0 with 14% aqueous ammonia.

 [0 1 5 3]

When glucose in the supernatant of the seed culture solution is consumed, 250 ml of the culture solution is collected aseptically, and glucose 5 g / L (separately sterilized), peptone (manufactured by Kyokuto Pharmaceutical Co., Ltd.) 5 g / L, phosphorus Disodium hydrogen oxyhydrogen 6g / L, dihydrogen phosphate 3g / L, ammonium chloride lg / L, magnesium sulfate heptahydrate 250mg / L (separate sterilization) and vitamin Bl 4mg / L (separate sterilization) ) Liquid medium consisting of the following composition (no pH adjustment) 2. Inoculate a 5L culture tank containing 5L, culture temperature 28 ° C, agitation 600rpm, aeration rate 2. 14% ammonia under culture conditions of 5L / min while adjusting to _{Ρ Η7} · 0 with water and culture was performed.

 During the culture, a feed solution composed of glucose 167 g / L and peptone 167 g / L was added at a rate of 30 ml / h by a peristaltic pump from the 11th to the 24th culture.

 [0 1 5 4]

Example 1 Put 500 ml of Corynebacterium ammoniagenes ATCC21170 culture solution obtained in 1 and 185 ml of Escherichia coli strain 294 CKG55 into a 2 L culture tank, and add glucose 48 g, magnesium sulfate heptahydrate 6. 25g, potassium dihydrogen phosphate 40g, xylene 14ml, orotic acid 5g were added to prepare a reaction solution. This reaction solution was stirred at 30 ° C at 800 rpm and aeration rate of 0.3 L / min. CTP production reaction was carried out while maintaining the pH at 7 and 4 with 10 mol / l K0H. Quantified by HPLC. As a result, 4.0 g / L (7.27 ol / l) of CTP was produced 20 hours after the start of the reaction. [0 1 5 5]

 (2) CTP production from cytosine

 Example 1 Corynepacteria ammoniagenes as in 1

The ATCC21170 / pRAl 43VTA35-1 strain was cultured, and the culture was terminated when the glucose in the supernatant was consumed. Corynebataterium ammoniagenes in 2L culture tank

ATCC21170 / pRA143VTA35-l strain 500 ml, glucose 48 g, magnesium sulfate heptahydrate 6.25 g, dihydrogen phosphate 40 g, xylene 14 ml, cytosine 5 g were added to prepare a reaction solution. The reaction was stirred 800rpm at 30 ° C, aeration rate under the conditions of 0. 3L / min, 10mol / l Gyoi the Tamochi'tsu 01? Reacting _P H 7. 4 at K0H of were produced CTP was quantified by HPLC. As a result, CTP was 14.0 in 20 hours from the start of the reaction.

g / L (25.4 ol / l) was produced.

 [0 1 5 6]

Example 1 5

 C D P—Choline production test

 Example 1 Corynebacterium ammoniagenes as in 1

The ATCC21170 / pRA143VTA35-l strain was cultured, and the culture was terminated when the glucose in the supernatant was consumed. Corynebatarum / Ammoniagenes in 2L culture tank

ATCC21170 / pRA143VTA35-1 strain 500 ml, Escherichia coli MM294 / pCKG55 strain 185 ml, glucose 48 g, choline chloride 8.4 g, magnesium sulfate heptahydrate 6.25 g, dihydrogen phosphate 40 ml, The reaction solution was prepared by adding 14 ml of xylene and 5 g of cytosine. This reaction solution was stirred at 30 ° C at 800 rpm and aeration rate of 0.3 L / min, and the CDP-choline production reaction was carried out while maintaining the pH at 7.4 with 10 mol / l K0H. CDP-choline was quantified by HPLC. As a result, 0.5 g / L (1.02 mmol) of CDP-choline was produced 20 hours after the start of the reaction.

 [0 1 5 7]

Example 1 6

 CMP-sialic acid production test

 (1) Preparation of Escherichia coli-derived CMP-sialic acid synthase expression strain

 The expression vector pTrS32 (FERM BP-5408) was enzymatically digested with Pstl and Hindlll, and a 3.5 kb DNA fragment was recovered. Similarly, pKYP10 (Japanese Patent Laid-Open No. 58-110600) was converted to Pstl and

The enzyme was digested with Hindlll and 1. The Okb fragment was recovered. The 3.5 kb fragment and 1. Okb fragment were ligated to obtain 4.5 kb pTrS31.

 a 3.5 kb DNA fragment obtained by enzymatic digestion of pTrS31 with Clal and Pstl;

obtained by enzymatic digestion of pPACl (FERM BP-6054, W0 98/12343) with Clal and Pstl

2. The 3 kb DNA fragment was ligated to obtain 5.8 kb pNT22.

[0 1 5 8] Using synthetic DNA having the nucleotide sequences represented by SEQ ID NOs: 28 and 29, a DNA fragment containing the CMP-sialic acid synthase gene neuA was amplified from the chromosomal DNA of Escherichia coli k235 strain (ATCC13027) by the following method. did.

 PCR was performed using Pyrobest DNA polymerase with the synthetic DNA as a primer set. 1/10 volume of the PCR reaction solution was subjected to agarose gel electrophoresis, and after confirming that the target fragment was amplified, the same amount of TE [10 mmol / l Tris-HC1, lmmol / 1 EDTA (pH 8.0)] Saturated phenol black form (lvol / vol) was added and mixed.

 [0 1 5 9]

 After centrifuging the mixture, the resulting upper layer was mixed with 2 volumes of cold ethanol and allowed to stand at −80 ° C. for 30 minutes. The solution was centrifuged to obtain a DNA precipitate, and the DNA precipitate was dissolved in 20 μl of TE. Using the lysate 5 / i 1, DNA was cleaved with restriction enzymes Hindlll and BamHI, and DNA fragments were separated by agarose gel electrophoresis, and then a 1.3 kb fragment was recovered.

 pBluescript Π SK (+) (Stratagene) 0.2 μg was cleaved with restriction enzymes Hindlll and BamHI, and then DNA fragments were separated by agarose gel electrophoresis. Similarly, a 2.9 kb DNA fragment was recovered.

 [0 1 6 0]

 Using a ligation kit, the fragments of 1.3 kb and 2.9 kb were subjected to ligation reaction at 16 ° C. for 16 hours. Using this ligation reaction solution, Escherichia coli orchid 522 was transformed according to a known method, and the obtained transformant was applied to an LB agar medium containing 50 / g / ml ampicillin and then incubated at 30 ° C. Cultured.

 From the culture obtained by culturing the grown transformant overnight at 30 ° C in LB liquid medium containing 50 μg / ml ampicillin, the plasmid was added using the automated nucleic acid separator PI50 manufactured by Kurabo Industries. Extracted.

 [0 1 6 1]

 The base sequence of the PCR-amplified fragment contained in the obtained plasmid was determined by a conventional method. As a result, it was found that the same base as neuA coding for CMP-sialic acid synthase derived from Escherichia coli described in GenBank ACCESSION No. J05023. It was an array.

 The plasmid was cleaved with ClaI and BamHI, and then the DNA fragments were separated by agarose gel electrophoresis to recover a 1.3 kb DNA fragment.

After cutting the PNT22 0. 2 μ _§ with restriction enzymes Cla I and BamH I, the DNA fragments were separated by Agarosugeru electrophoresis to recover a DNA fragment of similarly 5. 5 kb.

 [0 1 6 2]

Using a ligation kit, the fragments of 1.3 kb and 5.5 kb were subjected to ligation reaction at 16 ° C. for 16 hours. Escherichia col i NM522 is known using the ligation reaction solution The transformant was applied to an LB agar medium containing 50 Aig / ral ampicillin and cultured at 30 ° C.

 Plasmids were extracted using PI50 from the culture obtained by culturing the grown transformants in an LB liquid medium containing 50 / z g / ml ampicillin at 30 ° C. The structure of the plasmid was confirmed by restriction enzyme digestion, and the plasmid was named pTA23.

 Escherichia coli awake 522 was transformed again with pTA23, and the resulting transformant was named Escherichia coli NM522 / pTA23.

 [0 1 6 3]

 (2) CMP-sialic acid production test

Wherein How, Escherichia coli N 522 / pTA23 the L culture Chile ampicillin ⁵ 0 g / L Kutotoriputon (Difco) 10 g / L, yeast extract (Difco) 5 g / L, sodium chloride 5 g / L - Medium adjusted to pH 7.2] Inoculated into a 2 L baffled Erlenmeyer flask containing 200 ml, and cultured with shaking at 220 rpm for 24 hours at 25 ° C. 20 ml of this culture solution, glucose 5 g / L (separately sterilized), peptone (manufactured by Kyokuto Pharmaceutical Co., Ltd.) 5 g / L, disodium hydrogen phosphate 6 g / L, potassium dihydrogen phosphate 3 g / L, salt 匕 ammonium lg / L, Magnesium sulfate heptahydrate 250mg / L (separate sterilization) and vitamin Bl 4mg / L (separate sterilization) liquid medium (pH unadjusted) 2. Inoculate 5L culture tank containing 5L and, culturing temperature 28 ° C, was performed stirring 600 rpm, culture conditions aeration 2. 5L / min, culture while adjusting the _P H7. 0 with 14% aqueous ammonia. When glucose in the supernatant of the seed culture solution is consumed, 250 ml of the culture solution is collected aseptically, and glucose 5 g / L (separately sterilized), peptone (manufactured by Kyokuto Pharmaceutical Co., Ltd.) 5 g / L, phosphorus Nitrous acid hydrogen Λ 6g / L, Nitrogen hydrogen phosphate 3g / L, ammonium chloride lg / L, magnesium sulfate heptahydrate 250mg / L (separate sterilization) and vitamin Bl 4rag / L (separate sterilization) ) Liquid medium consisting of the following composition ( _P H unadjusted) 2. Inoculate a 5L culture tank containing 5L, culture temperature 28 ° C, stirring 600rpm, aeration 2. 14% under culture conditions of 5L / min Cultivation was performed while adjusting the pH to 7.0 using aqueous ammonia.

 During the culture, a feed solution composed of glucose 167 g / lepteptone 167 g / L was added by a peristaltic pump at a rate of 30 ml / h from the 11th to 24th culture.

 [0 1 6 4]

 Example 1 Corynepacteria ammoniagenes as in 1

The ATCC21170 / pRA143VTA35-l strain was cultured, and the culture was terminated when the glucose in the supernatant was consumed. Corynepacteria ammoniagenes in 2L culture tank

ATCC21170 RA143VTA35-1 strain 500 ml, Escherichia coli NM522 / pTA23 strain 185 ml, fructose 48 g, magnesium sulfate heptahydrate 6.25 g Potassium dihydrogen phosphate 40g, xylene 14ml, cytosine 5g and sialic acid 14g were added. CMP-sialic acid reaction was performed while maintaining the pH at 7.4 with 10 mol / l KOH under the conditions of 800 rpm stirring at 30 ° C and aeration rate of 0.3 L / min. Sialic acid was quantified by HPLC. As a result, 4.5 g / L (7.07 ol / l) of CMP-sialic acid was produced 20 hours after the start of the reaction.

 [Industrial applicability]

 [0165]

 According to the present invention, a protein having an activity of generating CMP from cytosine can be obtained. Using this protein, CMP can be produced inexpensively and efficiently.

 [Sequence Listing Free Text]

 [0166]

SEQ ID NO: 1 Description of one artificial sequence: Mutant protein

SEQ ID NO: 2—Description of artificial sequence: mutant protein

SEQ ID NO: 3—Description of artificial sequence: mutant DNA

SEQ ID NO: 4 Description of one artificial sequence: Mutant DNA

SEQ ID NO: 5—Description of artificial sequence: mutant DNA

SEQ ID NO: 7—Description of artificial sequence: synthetic DNA

SEQ ID NO: 8—Description of artificial sequence: synthetic DNA

SEQ ID NO: 10—Description of artificial sequence: synthetic DNA

SEQ ID NO: 1 1 Description of one artificial sequence: Synthetic DNA

SEQ ID NO: 13—Description of artificial sequence: synthetic DNA

SEQ ID NO: 14 Description of one artificial sequence: Synthetic DNA

SEQ ID NO: 17—Description of artificial sequence: synthetic DNA

SEQ ID NO: 18—Description of Artificial Sequence: Synthetic DNA

SEQ ID NO: 19 Description of One Artificial Sequence: Synthetic DNA

SEQ ID NO: 20 Description of one artificial sequence: synthetic DNA

SEQ ID NO: 21 Description of one artificial sequence: Synthetic DNA

SEQ ID NO: 22—Description of artificial sequence: synthetic DNA

SEQ ID NO: 23 Description of one artificial sequence: Synthetic DNA

SEQ ID NO: 24—Description of Artificial Sequence: Synthetic DNA

SEQ ID NO: 25 Description of one artificial sequence: Synthetic DNA

SEQ ID NO: 26 Description of one artificial sequence: Synthetic DNA

SEQ ID NO: 28 Description of One Artificial Sequence: Synthetic DNA

SEQ ID NO: 29 Description of One Artificial Sequence: Synthetic DNA

SEQ ID NO: 30 Description of one artificial sequence: Mutant protein SEQ ID NO: 34 Description of artificial sequence Synthetic DNA SEQ ID NO: 35 Description of artificial sequence Synthetic DNA SEQ ID NO: 36 Description of artificial sequence Synthetic DNA SEQ ID NO: 37 Description of artificial sequence Synthetic DNA SEQ ID NO: 38 Description of artificial sequence Mutant protein

Claims

[Document Name] Claim  [Claim 1] A method for producing a protein having an activity of producing cytidine 5′-monophosphate (CMP) from cytosine, comprising the following steps:  [I] uracil to uridine 5 '— UMP binding site in UPRTa se on a computer using part or all of the 3D structure information of protein (UPRTa se) that has the activity to generate monophosphate (UMP) Selecting one or more amino acid deletions, substitutions and / or additions in the amino acid sequence of UPRTase, which stabilizes a complex model of UPRTase and CMP produced by adapting CMP to  [2] A step of producing a UPRTase mutated protein comprising the deletion, substitution and / or addition selected in step [1].  [Claim 2] A method for producing a protein having an activity of producing cytidine 5′-monophosphate (CMP) from cytosine, comprising the following steps:  [II] From uracil to uridine 5'—a protein that has the activity of generating monophosphate (UMP) (UPRTa se), using a part or all of the three-dimensional structural information on the UMP binding site in UPRTa se on a computer. Selecting one or more amino acid deletions, substitutions and / or additions in the amino acid sequence of the UPRTase, which stabilizes the complex model of UPRTase and CMP produced by adapting the CMP;  [12] Deletion, substitution and / or addition of amino acids in the amino acid sequence of UPRTase, which stabilizes a multimeric model of the complex created on a computer using a part or all of the complex model Selecting one or more of; [13] A step of producing a UPRTase mutant protein comprising the deletion, substitution and / or addition selected in the steps [11] and [12].  [Claim 3] A protein obtained by the method according to claim 1 or 2.  [Claim 4] In the amino acid sequence described in SEQ ID NO: 15, the amino acid sequence has one to several amino acids deleted, substituted and / or added, Has the activity of generating CMP from cytosine, and Proteins containing one or more of the following amino acid substitutions: A part of the three-dimensional structural information of a protein (UP RT ase) comprising the amino acid sequence of SEQ ID NO: 15 represented by the three-dimensional coordinate atomic coordinates described in Table 1 and having an activity of generating UMP from uracil, or Create on the computer using the whole In the complex model of UP RT ase and UMP, a substitution of an amino acid in which a constituent atom exists in the range of 1 OA to 1 OA of the oxo group at the 4-position of the UMP pyrimidine ring, Substitution with an amino acid that stabilizes the complex model of UPRT as and CMP produced on a computer by converting the UMP group of UMP of the complex model to an amino group.  [Claim 5] 5. The protein according to claim 4, wherein the amino acid substitution is a substitution of glycine at position 205 of the amino acid sequence shown in SEQ ID NO: 15.  [Claim 6] 5. The protein according to claim 4, wherein the amino acid substitution is substitution of dasicine at position 205 of the amino acid sequence shown in SEQ ID NO: 15 with aspartic acid or glutamic acid. [Claim 7] 5. The protein according to claim 4, wherein the amino acid substitution is substitution of tyrosin at position 201 and proline at position 204 of the amino acid sequence represented by SEQ ID NO: 15.  [Claim 8] 5. The protein according to claim 4, wherein the amino acid substitution is substitution of tyrosine at position 201 with lysine and substitution of proline at position 204 with leucine in the amino acid sequence shown in SEQ ID NO: 15.  [Claim 9] In the complex model of UP RT ase and UMP described above, substitution of an amino acid having a constituent atom in the range of one OA to 1 OA from any atom constituting UMP (however, oxygen atom of oxo group at 4-position of pyrimidine ring of UMP) 1 to 1 OA), and includes one or more amino acid substitutions that stabilize the complex model of UPRTase and CMP. The protein according to any one of the above.  [Claim 10] Part or all of the three-dimensional structural information of the protein (UP RT ase) consisting of the amino acid sequence of SEQ ID NO: 15 represented by the three-dimensional coordinate atomic coordinates described in Table 1 and having the activity of generating UMP from uracil In a complex model of UPRTase and phosphoribosyl pyrophosphate (PRPP), which is created on a computer using, a substitution of an amino acid having a constituent atom in the range of one OA to 1 OA from any atom constituting PRPP. The protein according to any one of claims 4 to 8, which comprises one or more amino acid substitutions that stabilize the complex model. [Claim 1 1] In a multimeric model of a complex created on a computer using a part or all of the complex model of UP RT ase and CMP described above, any one of the adjacent UP RT ase monomer atoms An amino acid having a constituent atom within A and an amino acid selected from the group consisting of an amino acid having a constituent atom within 5 A from any of the constituent atoms of position 66 Trp of the adjacent UP RTase monomer Substitution with an amino acid that stabilizes the multimeric model. The protein according to any one of claims 4 to 10, comprising one or more of the above.  [Claim 12] A protein having an amino acid sequence represented by SEQ ID NO: 1, 2, or 30 having an activity of producing cytidine 5′-monophosphate (CMP) from cytosine.  [Claim 13] In the amino acid sequence represented by SEQ ID NO: 1, 2, or 30, one or more amino acid residues selected from the 36th, 94th, 102nd, 141st, 143rd and 198th amino acid residues are other A protein having an amino acid sequence substituted with an amino acid residue and having an activity of generating CMP from cytosine.  [Claim 14]  36th amino acid residue is cysteine, 94th amino acid residue is tyrosine, 102nd amino acid residue is cysteine, 141st amino acid residue is oral isine, 143rd amino acid residue is palin, or 198th 13. The protein according to claim 12, wherein the amino acid residue has an amino acid sequence substituted with glycine.  [Claim 15] In the amino acid sequence represented by SEQ ID NO: 1, 2, or 30, from the amino acid residue at position 36, 46, 94, 102, 121, 141, 143, 16 7 and 1 98 A protein having an amino acid sequence in which one or more selected amino acid residues are substituted with other amino acid residues, and having an activity of generating CMP from cytosine.  [Claim 16] The amino acid sequence of the protein according to any one of claims 12 to 15, wherein the amino acid other than the 3rd, 94th, 102nd, 141st, 143rd, 198th, 20th, 204th and 20.5th amino acids A protein having an amino acid sequence in which one or more amino acid residues selected from residues are substituted with other amino acid residues, and having an activity of generating CMP from cytosine.  [Claim 1 7] The amino acid sequence of the protein according to any one of claims 12 to 15, wherein: 36, 46, 94, 102, 121, 141, 143, 167, 198, 201, 204th and 205th A protein having an amino acid sequence in which one or more amino acid residues selected from other amino acid residues are replaced with other amino acid residues, and having an activity of generating CMP from cytosine.  [Claim 18] DNA according to [1] or [2] below.  [1] DNA encoding the protein according to any one of claims 3 to 17  [2] D N A having a base sequence represented by a deviation or deviation of SEQ ID NOs: 3 to 5  [Claim 19] A recombinant DNA comprising the DNA of claim 18.  [Claim 20] A microorganism having the recombinant DNA according to claim 19.  [Claim 21] 21. The microorganism according to claim 20, wherein the microorganism is a microorganism belonging to the genus Escherichia, Corynebacterium, or Brevibaterium.  [Claim 22] A microorganism culture according to claim 20 or 21 or a treated product thereof, cytosine, a phosphate group donor and an energy donor are present in an aqueous medium, and CMP is produced and accumulated in the medium. A method for producing CMP, characterized in that CMP is collected from the medium.  [Claim 23] 22. The microorganism culture according to claim 20 or 21, or a treatment product of the culture, a culture of a microorganism belonging to the genus Corynebacterium, or a treatment product of the culture, cytosine, a phosphate group donor, and an energy donor. A method for producing CMP, characterized by being present in a medium, generating and accumulating CMP in the medium, and collecting the CMP from the medium.  [Claim 24] 24. The production method according to claim 23, wherein the microorganism belonging to the genus Corynebacterium is corynebacterium ammoniagenes.  [Claim 25] A microorganism culture or a treated product of the culture according to claim 20 or 21, cytosine, a phosphate donor and an energy donor are present in an aqueous medium, and CMP is used to produce the medium in the medium. A process for producing useful substances.