NOVEL GENETICALLY ENGINEERED VACCINIA VIRUSES

Abstract

The present invention provides a genetically recombinant vaccinia virus effective in preventing or treating cancer. Specifically, the present invention provides a vaccinia virus comprising two polynucleotides, a polynucleotide encoding IL-7 and a polynucleotide encoding IL-12; a combination kit of two vaccinia viruses, a vaccinia virus comprising a polynucleotide encoding IL-7 and a vaccinia virus comprising a polynucleotide encoding IL-12; and use of the two vaccinia viruses in combination.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is Continuation of PCT/JP2017/019921, filed May 29, 2017, which claims priority from Japanese application JP 2016-107481, filed May 30, 2016.

[0002] The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-WEB and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Jul. 27, 2017, is named sequence.txt and is 275 KB.

BACKGROUND OF THE INVENTION

Field of the Invention

[0003] The present invention relates to a novel genetically engineered vaccinia virus.

Description of the Related Art

[0004] Various techniques for using viruses for cancer treatments have been recently developed. Vaccinia virus is one of the viruses used for cancer treatment. Vaccinia virus has been studied for the cancer treatment as a vector for delivering therapeutic genes to cancer cells, as an oncolytic virus that proliferates in cancer cells and destroys the cancer cells, or as a cancer vaccine that expresses tumor antigens or immunomodulatory molecules (Expert Opinion on Biological Therapy, 2011, vol. 11, p. 595-608).

[0005] Vaccinia viruses engineered so as to have an N1L gene inactivated by the insertion of a foreign gene encoding interleukin-12 (IL-12) or interleukin-21 (IL-21) and to be deficient in the thymidine kinase (TK) gene by the insertion of the lacZ reporter gene and the firefly luciferase gene have been reported to suppress the tumor growth or improve the survival rate in cancer-bearing mice (Patent Literature 1).

[0006] A technique for employing, for cancer treatment, recombinant vaccinia viruses that are deficient in the function of the viral proteins vaccinia virus growth factor (VGF) and O1L and proliferate specifically in cancer cells and destroy the cancer cells has been reported. Although it is stated that a foreign gene such as a marker gene or a therapeutic gene encoding a product having cytotoxicity or the immunopotentiating effect may be introduced into a gene that is not essential to the life cycle of vaccinia virus, the introduction of a gene specifically examined in Examples is that of a marker gene, a luciferase-green fluorescent protein (GFP) fusion gene or an expression cassette of DsRed. No therapeutic gene is examined for the introduction. No suggestion is made for combining plural therapeutic genes (Patent Literature 2).

[0007] Meanwhile, it has been reported that, in the examination of effects of recombinant proteins on isolated CD8.sup.+T cells, a recombinant human interleukin-7 (IL-7) protein alone does not induce detectable levels of interferon-gamma (IFN-.gamma.) production by CD8.sup.+T cells, but a combination of the recombinant human IL-7 protein and a recombinant human IL-12 protein synergistically enhances the production of IFN-.gamma. (The Journal of Immunology, 1995, vol. 154, p. 5093-5102). It has been reported that an oncolytic vaccinia virus that expresses an immune-stimulating molecule may rapidly be cleared by strong immune responses. It is also stated that strong immune response could serve either as a foe or as an ally to the vaccinia virus-mediated cancer therapy (Molecular Therapy, 2005, vol. 11, No. 2, p. 180-195).

CITATION LIST

Patent Literatures

[0008] Patent Literature 1: WO2015/150809

[0009] Patent Literature 2: WO2015/076422

SUMMARY OF THE INVENTION

Technical Problem

[0010] An object of the present invention is to provide a recombinant vaccinia virus (in particular, oncolytic vaccinia virus), a pharmaceutical composition and a combination kit, for treating or preventing cancer.

Solution to Problem

[0011] As a result of considerable repetitive thinking and studies in the generation of vaccinia virus, the present inventors have generated vaccinia viruses comprising a polynucleotide encoding IL-7 or vaccinia viruses comprising a polynucleotide encoding IL-12, and vaccinia viruses comprising two polynucleotides, a polynucleotide encoding IL-7 and a polynucleotide encoding IL-12 (Example 2); and found that 1) a vaccinia virus comprising two polynucleotides, a polynucleotide encoding IL-7 and a polynucleotide encoding IL-12 and 2) a mixture of two vaccinia viruses, a vaccinia virus comprising a polynucleotide encoding IL-7 and a vaccinia virus comprising a polynucleotide encoding IL-12 exhibit a cytolytic effect on various human cancer cells (Example 3), thereby completing the present invention:

1) a vaccinia virus comprising two polynucleotides, a polynucleotide encoding IL-7 and a polynucleotide encoding IL-12 could exhibit a tumor regression effect in cancer-bearing humanized mouse models (Example 6), could achieve complete remission (Example 7), and could induce acquired immunity to maintain the antitumor effect (Example 8) in syngeneic cancer-bearing mouse models. Moreover, 2) a mixture of two vaccinia viruses, a vaccinia virus comprising a polynucleotide encoding IL-7 and a vaccinia virus comprising a polynucleotide encoding IL-12 could achieve complete remission (Example 7), and could induce acquired immunity to maintain the antitumor effect (Example 8) in syngeneic cancer-bearing mouse models.

[0012] More specifically, the present invention may encompass, as a substance or method useful in medicine or industry, the following inventions:

[1] A vaccinia virus comprising the following (1) and (2): (1) a polynucleotide encoding interleukin-7 (IL-7); and (2) a polynucleotide encoding interleukin-12 (IL-12). [2] A pharmaceutical composition selected from the following (1) or (2): (1) a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-12 to be used in combination with a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-7; or (2) a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-7 to be used in combination with a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-12. [3] A combination kit comprising the following vaccinia viruses (1) and (2): (1) a vaccinia virus comprising a polynucleotide encoding IL-7; and (2) a vaccinia virus comprising a polynucleotide encoding IL-12. [4] The vaccinia virus according to [1], wherein the vaccinia virus is deficient in the function of vaccinia virus growth factor (VGF). [5] The vaccinia virus according to [1], wherein the vaccinia virus is deficient in the function of O1L. [6] The vaccinia virus according to [1], wherein the vaccinia virus is deficient in the functions of VGF and O1L. [7] The vaccinia virus according to [1], wherein the vaccinia virus has a deletion in the short consensus repeat (SCR) domains in the B5R extracellular region. [8] The vaccinia virus according to [1], wherein the vaccinia virus is deficient in the functions of VGF and O1L and has a deletion in the SCR domains in the B5R extracellular region. [9] The vaccinia virus according to any one of [1] and [4]-[8], wherein the vaccinia virus is a LC16mO strain. [10] A pharmaceutical composition comprising a vaccinia virus according to any one of [1] and [4]-[9] and a pharmaceutically acceptable excipient. [11] The pharmaceutical composition according to [2] or the kit according to [3], wherein the vaccinia virus is deficient in the function of VGF. [12] The pharmaceutical composition according to [2] or the kit according to [3], wherein the vaccinia virus is deficient in the function of O1L. [13] The pharmaceutical composition according to [2] or the kit according to [3], wherein the vaccinia virus is deficient in the functions of VGF and O1L. [14] The pharmaceutical composition according to [2] or the kit according to [3], wherein the vaccinia virus has a deletion in the SCR domains in the B5R extracellular region. [15] The pharmaceutical composition according to [2] or the kit according to [3], wherein the vaccinia virus is deficient in the functions of VGF and O1L and has a deletion in the SCR domains in the B5R extracellular region. [16] The pharmaceutical composition according to any one of [2] and [11]-[15] or the kit according to any one of [3] and [11]-[15], wherein the vaccinia virus is a LC16mO strain. [17] The pharmaceutical composition according to any one of [2] and [11]-[16] or the kit according to any one of [3] and [11]-[16], further comprising a pharmaceutically acceptable excipient. [18] The pharmaceutical composition or kit according to any one of [10]-[17], for preventing or treating cancer. [19] The pharmaceutical composition or kit according to [18], wherein the cancer is malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer or gastric cancer. [20] A method for preventing or treating cancer, comprising the step of administering the vaccinia virus according to any one of [1] and [4]-[9] to a subject in need of the prevention or treatment for cancer. [21] The method according to [20], wherein the cancer is malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer or gastric cancer. [22] The vaccinia virus according to any one of [1] and [4]-[9], for use in preventing or treating cancer. [23] The vaccinia virus according to [22], wherein the cancer is malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer or gastric cancer. [24] Use of the vaccinia virus according to any one of [1] and [4]-[9] for the manufacture of a pharmaceutical composition for preventing or treating cancer. [25] The use according to [24], wherein the cancer is malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer or gastric cancer. [26] A method for preventing or treating cancer, comprising the step of administering (1) a vaccinia virus comprising a polynucleotide encoding IL-7; and (2) a vaccinia virus comprising a polynucleotide encoding IL-12 to a subject in need of the prevention or treatment for cancer. [27] The method according to [26], wherein the cancer is malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer or gastric cancer. [28] A vaccinia virus selected from the following (1) or (2): (1) a vaccinia virus comprising a polynucleotide encoding IL-7, for preventing or treating cancer in combination with a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-12; or (2) a vaccinia virus comprising a polynucleotide encoding IL-12, for preventing or treating cancer in combination with a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-7. [29] The vaccinia virus according to [28], wherein the cancer is malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer or gastric cancer. [30] Use of a vaccinia virus selected from the following (1) or (2): (1) use of a vaccinia virus comprising a polynucleotide encoding IL-7 for the manufacture of a pharmaceutical composition for preventing or treating cancer to be used in combination with a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-12; or (2) use of a vaccinia virus comprising a polynucleotide encoding IL-12 for the manufacture of a pharmaceutical composition for preventing or treating cancer to be used in combination with a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-7. [31] The use according to [30], wherein the cancer is malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer or gastric cancer. [32] Use of (1) a vaccinia virus comprising a polynucleotide encoding IL-7 and (2) a vaccinia virus comprising a polynucleotide encoding IL-12 for the manufacture of a combination kit for preventing or treating cancer. [33] The use according to [32], wherein the cancer is malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer or gastric cancer.

Advantageous Effects of the Invention

[0013] The vaccinia virus according to the present invention and the vaccinia viruses contained in the pharmaceutical composition and combination kit according to the present invention exhibit oncolytic activity, express IL-12 and IL-7 polypeptides encoded by polynucleotides carried by the viruses in cancer cells, and induce complete remission and acquired immunity. The vaccinia virus, pharmaceutical composition, and combination kit according to the present invention can be used for preventing or treating cancer.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] FIG. 1 is a drawing illustrating an example of transfer vector plasmid DNAs used in the present invention, in which the upper map illustrates an example in which the BFP gene operably linked to a promoter is incorporated in the VGF gene and the lower map illustrates an example in which the BFP gene operably linked to a promoter is incorporated in the O1L gene;

[0015] FIG. 2 is a schematic view of the genome structure of recombinant vaccinia viruses (LC16mO .DELTA.SCR VGF-p7.5-DsRed/O1L-SP-LacZ and viruses constructed in the process of generating the virus vector);

[0016] FIG. 3 is a schematic view of the genome structure of recombinant vaccinia viruses (LC16mO .DELTA.SCR VGF-SP-IL12/O1L-SP-LacZ, LC16mO .DELTA.SCR VGF-SP-IL7/O1L-SP-LacZ);

[0017] FIG. 4 is a schematic view of the genome structure of a recombinant vaccinia virus (LC16mO .DELTA.SCR VGF-SP-IL12/O1L-SP-IL7);

[0018] FIG. 5A is a graph illustrating oncolytic properties of a recombinant vaccinia virus (LC16mO .DELTA.SCR VGF-SP-IL12/O1L-SP-IL7), in which the ordinate represents the cancer cell survival rate (%) and the error bars represent standard deviation;

[0019] FIG. 5B is a graph illustrating oncolytic properties of a recombinant vaccinia virus (LC16mO .DELTA.SCR VGF-SP-IL12/O1L-SP-IL7), in which the ordinate represents cancer cell survival rate (%) and the error bars represents standard deviation, FIG. 5A and FIG. 5B being graphs obtained under the same experimental conditions except that the cell types measured were different;

[0020] FIG. 5C is a graph illustrating oncolytic properties of a mixture of 2 recombinant vaccinia viruses (a mixture of LC16mO .DELTA.SCR VGF-SP-IL12/O1L-SP-LacZ and LC16mO .DELTA.SCR VGF-SP-IL7/O1L-SP-LacZ), in which the ordinate represents cancer cell survival rate (%) and the error bars represent standard deviation;

[0021] FIG. 5D is a graph illustrating oncolytic properties of a mixture of 2 recombinant vaccinia viruses (a mixture of LC16mO .DELTA.SCR VGF-SP-IL12/O1L-SP-LacZ and LC16mO .DELTA.SCR VGF-SP-IL7/O1L-SP-LacZ), in which the ordinate represents cancer cell survival rate (%) and the error bars represent standard deviation, FIG. 5C and FIG. 5D being graphs obtained under the same experimental conditions except that the cell types measured were different.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] The present invention is described in detail below.

<Vaccinia Virus, Pharmaceutical Composition to be Used in Combination and Combination Kit According to the Present Invention>

[0023] The present invention provides a vaccinia virus comprising the following (1) and (2):

(1) a polynucleotide encoding IL-7; and (2) a polynucleotide encoding IL-12. (As used herein, the vaccinia virus is also referred to as the "vaccinia virus according to the present invention".)

[0024] The present invention also provides a pharmaceutical composition selected from the following (1) or (2):

(1) a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-12 to be used in combination with a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-7; or (2) a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-7 to be used in combination with a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-12. (As used herein, the pharmaceutical composition is also referred to as the "pharmaceutical composition to be used in combination according to the present invention" and a vaccinia virus comprising a polynucleotide encoding IL-7 or a vaccinia virus comprising a polynucleotide encoding IL-12 contained in the pharmaceutical composition to be used in combination according to the present invention described in (1) or (2) above is also referred to as the "vaccinia virus to be used in combination".)

[0025] The present invention also provides a combination kit comprising the following vaccinia viruses (1) and (2):

(1) a vaccinia virus comprising a polynucleotide encoding IL-7; and (2) a vaccinia virus comprising a polynucleotide encoding IL-12. (As used herein, the combination kit is also referred to as the "combination kit according to the present invention" and the vaccinia viruses contained in the combination kit according to the present invention are also referred to as the "vaccinia viruses for the combination kit".)

[0026] The combination kit according to the present invention means one or more pharmaceutical compositions to be used to administer two vaccinia viruses: (1) a vaccinia virus comprising a polynucleotide encoding IL-7 and (2) a vaccinia virus comprising a polynucleotide encoding IL-12. When both vaccinia viruses are administered simultaneously, the combination kit can contain the two vaccinia viruses for the combination kit together in a single pharmaceutical composition such as a powder or separately in plural pharmaceutical compositions. The combination kit according to the present invention encompasses a pharmaceutical composition containing two vaccinia viruses: a vaccinia virus comprising a polynucleotide encoding IL-7 and a vaccinia virus comprising a polynucleotide encoding IL-12. When both vaccinia viruses for the combination kit are not simultaneously administered, the combination kit contains the two vaccinia viruses for the combination kit in separate pharmaceutical compositions. For example, the combination kit comprises the two vaccinia viruses for the combination kit in separate pharmaceutical compositions in a single package or in separate pharmaceutical compositions in separate packages. The combination kit according to the present invention may comprise a pharmaceutically acceptable excipient.

[0027] The vaccinia virus used for the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, and the vaccinia viruses for the combination kit is a virus in the genus Orthopoxvirus in the family Poxviridae. Strains of the vaccinia virus used in the present invention include, but not limited to, the strains Lister, New York City Board of Health (NYBH), Wyeth, Copenhagen, Western Reserve (WR), Modified Vaccinia Ankara (MVA), EM63, Ikeda, Dalian, Tian Tan, and the like. The strains Lister and MVA are available from American Type Culture Collection (ATCC VR-1549 and ATCC VR-1508, respectively). Furthermore, vaccinia virus strains established from these strains may be used in the present invention. For example, the strains LC16, LC16m8, and LC16mO established from the strain Lister may be used in the present invention. The strain LC16mO is a strain generated via the strain LC16 by subculturing at low temperature the Lister strain as the parent strain. The LC16m8 strain is a strain generated by further subculturing at low temperature the strain LC16mO, having a frameshift mutation in the B5R gene, a gene encoding a viral membrane protein, and attenuated by losing the expression and the function of this protein (Tanpakushitsu kakusan koso (Protein, Nucleic acid, Enzyme), 2003, vol. 48, p. 1693-1700). The whole genome sequences of the strains Lister, LC16m8, and LC16mO are known as, for example, Accession No. AY678276.1, Accession No. AY678275.1, and Accession No. AY678277.1, respectively. Therefore, the strains LC16m8 and LC16mO can be made from the strain Lister by a known technique, such as homologous recombination or site-directed mutagenesis.

[0028] In one embodiment, the vaccinia virus used in the present invention is the strain LC16mO.

[0029] The vaccinia virus used in the present invention can include attenuated and/or tumor-selective vaccinia viruses. As used herein, "attenuated" means low toxicity (for example, cytolytic property) to normal cells (for example, non-tumor cells). As used herein, "tumor selective" means toxicity to tumor cells (for example, oncolytic) higher than that to normal cells (for example, non-tumor cell). Vaccinia viruses genetically modified to be deficient in the function of a specific protein or to suppress the expression of a specific gene or protein (Expert Opinion on Biological Therapy, 2011, vol. 11, p. 595-608) may be used in the present invention. For example, in order to increase tumor selectivity of vaccinia virus, vaccinia virus deficient in the function of TK (Cancer Gene Therapy, 1999, vol. 6, p. 409-422), vaccinia virus deficient in the function of VGF (Cancer Research, 2001, vol. 61, p. 8751-8757), vaccinia virus having a modified TK gene, a modified hemagglutinin (HA) gene, and a modified F3 gene or an interrupted F3 locus (WO 2005/047458), vaccinia virus deficient in the function of VGF and O1L (WO 2015/076422), vaccinia virus in which a target sequence of a microRNA whose expression is decreased in cancer cells is inserted into the 3' noncoding region of the B5R gene (WO 2011/125469), vaccinia virus deficient in the function of VGF and TK (Cancer Research, 2001, vol. 61, p. 8751-8757), vaccinia virus deficient in the function of TK, HA, and F14.5L (Cancer Research, 2007, vol. 67, p. 10038-10046), vaccinia virus deficient in the function of TK and B18R (PLoS Medicine, 2007, vol. 4, p. e353), vaccinia virus deficient in the function of TK and ribonucleotide reductase (PLoS Pathogens, 2010, vol. 6, p. e1000984), vaccinia virus deficient in the function of SPI-1 and SPI-2 (Cancer Research, 2005, vol. 65, p. 9991-9998), vaccinia virus deficient in the function of SPI-1, SPI-2, and TK (Gene Therapy, 2007, vol. 14, p. 638-647), or vaccinia virus having mutations in the E3L and K3L regions (WO 2005/007824) may be used. Moreover, vaccinia virus deficient in the function of O1L may be used (Journal of Virology, 2012, vol. 86, p. 2323-2336). Moreover, in hope that the clearance of virus by the neutralization effect of anti-vaccinia virus antibodies is reduced in the living body, vaccinia virus deficient in the extracellular region of B5R (Virology, 2004, vol. 325, p. 425-431) or vaccinia virus deficient in the A34R region (Molecular Therapy, 2013, vol. 21, p. 1024-1033) may be used. Moreover, in hope of the activation of immune cells by vaccinia virus, vaccinia virus deficient in interleukin-1b (IL-1b) receptor (WO 2005/030971) may be used. Such insertion of a foreign gene or deletion or mutation of a gene can be made, for example, by a known homologous recombination or site-directed mutagenesis. Moreover, vaccinia virus having a combination of such genetic modifications may be used in the present invention. As used herein, "being deficient" means that the gene region specified by this term has no function and used in a meaning including deletion of the gene region specified by this term. For example, "being deficient" may be a result of the deletion in a region consisting of the specified gene region or the deletion in a neighboring gene region comprising the specified gene region.

[0030] In one embodiment, the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit is (are) deficient in the function of VGF. In one embodiment, the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit is (are) deficient in the function of O1L. In one embodiment, the vaccinia virus according to the present invention, the vaccinia virus to be used in combination or the vaccinia viruses for the combination kit is (are) deficient in the functions of VGF and O1L. The function of VGF and/or O1L may be made deficient in vaccinia virus based on the method described in WO 2015/076422.

[0031] VGF is a protein having a high amino acid sequence homology with epidermal growth factor (EGF), binds to the epidermal growth factor receptor like EGF, and activates the signal cascade from Ras, Raf, Mitogen-activated protein kinase (MAPK)/the extracellular signal-regulated kinase (ERK) kinase (MAPK/ERK kinase, MEK), and to following ERK to promote the cell division.

[0032] O1L maintains the activation of ERK and contributes to the cell division along with VGF.

[0033] Being deficient in the function of VGF and/or O1L of vaccinia virus refers to loss of the expression of the gene encoding VGF and/or the gene encoding O1L or the normal function of VGF and/or O1L when expressed. The deficiency in the function of VGF and/or O1L of vaccinia virus may be caused by the deletion of all or a part of the gene encoding VGF and/or the gene encoding O1L. Moreover, the genes may be mutated by nucleotide substitution, deletion, insertion, or addition to prevent the expression of normal VGF and/or O1L. Moreover, a foreign gene may be inserted in the gene encoding VGF and/or the gene encoding O1L. In the present invention, a gene is stated to be deficient when the normal product of the gene is not expressed by mutation such as genetic substitution, deletion, insertion, or addition.

[0034] Whether or not the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit is (are) deficient in the function of VGF and/or O1L may be determined with a known method, for example, by evaluating the function of VGF and/or O1L, testing for the presence of VGF or O1L by an immunochemical technique using an antibody against VGF or an antibody against O1L, or determining the presence of the gene encoding VGF or the gene encoding O1L by the polymerase chain reaction (PCR).

[0035] B5R (Accession No. AAA48316.1) is a type 1 membrane protein resides in the envelope of vaccinia virus, and serves to increase the infection efficiency when the virus infects and is transmitted to neighboring cells or other sites in the host. The extracellular region of B5R contains 4 structural domains called SCR domains (Journal of Virology, 1998, vol. 72, p. 294-302). In one embodiment, the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit has (have) a deletion in the SCR domains in the extracellular region of B5R.

[0036] The deletion in the SCR domains in the B5R extracellular region of vaccinia virus encompasses the deletion of a part or all of the 4 SCR domains in the B5R extracellular region and refers to the lack of expression of a gene region encoding a part or all of the 4 SCR domains in the B5R extracellular region or the lack of a part or all of the 4 SCR domains in the extracellular region in the expressed B5R protein. In one embodiment, the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit has (have) the deletion of all 4 SCR domains. In one embodiment, the 4 SCR domains deleted in the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, and the vaccinia viruses for the combination kit correspond to the region from amino acid 22 to amino acid 237 in the amino acid sequence of Accession No. AAA48316.1 described above.

[0037] Whether or not the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit has (have) a deletion in the SCR domains in the B5R extracellular region can be determined with a known method, for example, by testing for the presence of the SCR domains by an immunochemical technique using an antibody against the SCR domains or determining the presence or the size of the gene encoding the SCR domains by PCR.

[0038] In one embodiment, the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit is (are) vaccinia virus deficient in the functions of VGF and O1L and having a deletion in the SCR domains in the B5R extracellular region.

[0039] In one embodiment, the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit is (are) vaccinia virus of the strain LC16mO deficient in the functions of VGF and O1L and having a deletion in the SCR domains in the B5R extracellular region.

[0040] In one embodiment, the vaccinia virus according to the present invention is vaccinia virus comprising a polynucleotide encoding IL-7 and a polynucleotide encoding IL-12 and being deficient in the functions of VGF and O1L.

[0041] In one embodiment, the vaccinia virus according to the present invention is vaccinia virus of the strain LC16mO comprising a polynucleotide encoding IL-7 and a polynucleotide encoding IL-12 and being deficient in the functions of VGF and O1L.

[0042] In one embodiment, the vaccinia virus according to the present invention is vaccinia virus comprising a polynucleotide encoding IL-7 and a polynucleotide encoding IL-12, being deficient in the functions of VGF and O1L, and having a deletion in the SCR domains in the B5R extracellular region.

[0043] In one embodiment, the vaccinia virus according to the present invention is vaccinia virus of the strain LC16mO comprising a polynucleotide encoding IL-7 and a polynucleotide encoding IL-12, being deficient in the functions of VGF and O1L, and having a deletion in the SCR domains in the B5R extracellular region.

[0044] In one embodiment, the vaccinia virus to be used in combination or the vaccinia viruses for the combination kit is (are) vaccinia virus comprising a polynucleotide encoding IL-7 and being deficient in the functions of VGF and O1L or vaccinia virus comprising a polynucleotide encoding IL-12 and being deficient in the functions of VGF and O1L.

[0045] In one embodiment, the vaccinia virus to be used in combination or the vaccinia viruses for the combination kit is (are) vaccinia virus of the strain LC16mO comprising a polynucleotide encoding IL-7 and being deficient in the functions of VGF and O1L or vaccinia virus of the strain LC16mO comprising a polynucleotide encoding IL-12 and being deficient in the functions of VGF and O1L.

[0046] In one embodiment, the vaccinia virus to be used in combination or the vaccinia viruses for the combination kit is (are) vaccinia virus comprising a polynucleotide encoding IL-7, being deficient in the functions of VGF and O1L, and having a deletion in the SCR domains in the B5R extracellular region or vaccinia virus comprising a polynucleotide encoding IL-12, being deficient in the functions of VGF and O1L, and having a deletion in the SCR domains in the B5R extracellular region.

[0047] In one embodiment, the vaccinia virus to be used in combination or the vaccinia viruses for the combination kit is (are) vaccinia virus of the strain LC16mO comprising a polynucleotide encoding IL-7, being deficient in the functions of VGF and O1L and having a deletion in the SCR domain in the B5R extracellular region or vaccinia virus of the strain LC16mO comprising a polynucleotide encoding IL-12, being deficient in the functions of VGF and O1L, and having a deletion in the SCR domains in the B5R extracellular region.

[0048] IL-7 is a secretory protein functioning as an agonist for the IL-7 receptor. It is reported that IL-7 contributes to the survival, proliferation, and differentiation of T cells, B cells, or the like (Current Drug Targets, 2006, vol. 7, p. 1571-1582). In the present invention, IL-7 encompasses IL-7 occurring naturally and modified forms having the function thereof. In one embodiment, IL-7 is human IL-7. In the present invention, human IL-7 encompasses human IL-7 occurring naturally and modified forms having the function thereof. In one embodiment, human IL-7 is selected from the group consisting of the following (1) to (3):

(1) a polypeptide comprising the amino acid sequence set forth in Accession No. NP_000871.1 and having the function of human IL-7; (2) a polypeptide consisting of an amino acid sequence in which 1 to 10 amino acids are deleted from, substituted in, inserted into, and/or added to the amino acid sequence set forth in Accession No. NP_000871.1 and having the function of human IL-7; and (3) a polypeptide comprising an amino acid sequence having a 90% or more identity with the amino acid sequence set forth in Accession No. NP_000871.1 and having the function of human IL-7.

[0049] In relation with this, the function of human IL-7 refers to the effect on the survival, proliferation, and differentiation of human immune cells.

[0050] Human IL-7 used in the present invention is preferably a polypeptide consisting of the amino acid sequence set forth in Accession No. NP_000871.1.

[0051] IL-12 is a heterodimer of the IL-12 subunit p40 and the IL-12 subunit .alpha.. IL-12 has been reported to have the function of activating and inducing the differentiation of T cells and NK cells (Cancer Immunology Immunotherapy, 2014, vol. 63, p. 419-435). In the present invention, IL-12 encompasses IL-12 occurring naturally and modified forms having the function thereof. In one embodiment, IL-12 is human IL-12. In the present invention, human IL-12 encompasses human IL-12 occurring naturally and modified forms having the function thereof. In one embodiment, human IL-12 is selected, as a combination of the human IL-12 subunit p40 and the human IL-12 subunit .alpha., from the group consisting of the following (1) to (3):

(1) polypeptides comprising (1-a) a polypeptide comprising the amino acid sequence set forth in Accession No. NP_002178.2, (1-b) a polypeptide consisting of an amino acid sequence in which 1 to 10 amino acids are deleted from, substituted in, inserted into, and/or added to the amino acid sequence set forth in Accession No. NP_002178.2, or (1-c) a polypeptide comprising an amino acid sequence having a 90% or more identity with the amino acid sequence set forth in Accession No. NP_002178.2; and (2-a) a polypeptide comprising the amino acid sequence set forth in Accession No. NP_000873.2, (2-b) a polypeptide consisting of an amino acid sequence in which 1 to 10 amino acids are deleted from, substituted in, inserted into, and/or added to the amino acid sequence set forth in Accession No. NP_000873.2, or (2-c) a polypeptide comprising an amino acid sequence having a 90% or more identity with the amino acid sequence set forth in Accession No. NP_000873.2, and having the function of human IL-12; (2) polypeptides comprising (1-a) a polypeptide consisting of the amino acid sequence set forth in Accession No. NP_002178.2, and (2-a) a polypeptide comprising the amino acid sequence set forth in Accession No. NP_000873.2, (2-b) a polypeptide consisting of an amino acid sequence in which 1 to 10 amino acids are deleted from, substituted in, inserted into, and/or added to the amino acid sequence set forth in Accession No. NP_000873.2, or (2-c) a polypeptide comprising an amino acid sequence having a 90% or more identity with the amino acid sequence set forth in Accession No. NP_000873.2, and having the function of human IL-12; and (3) a polypeptide comprising (1-a) a polypeptide comprising the amino acid sequence set forth in Accession No. NP_002178.2, (1-b) a polypeptide consisting of an amino acid sequence in which 1 to 10 amino acids are deleted from, substituted in, inserted into, and/or added to the amino acid sequence set forth in Accession No. NP_002178.2, or (1-c) a polypeptide comprising an amino acid sequence having a 90% or more identity with the amino acid sequence set forth in Accession No. NP_002178.2, and (2-a) a polypeptide consisting of the amino acid sequence set forth in Accession No. NP_000873.2, and having the function of human IL-12.

[0052] In relation with this, the function of human IL-12 refers to activating and/or differentiating effects on T cells or NK cells. The IL-12 subunit p40 and the IL-12 subunit .alpha. can form IL-12 by direct binding. Moreover, the IL-12 subunit p40 and the IL-12 subunit .alpha. can be conjugated via a linker.

[0053] Human IL-12 used in the present invention is preferably a polypeptide comprising a polypeptide consisting of the amino acid sequence set forth in Accession No. NP_002178.2 and a polypeptide consisting of the amino acid sequence set forth in Accession No. NP_000873.2.

[0054] As used herein, "identity" means the value Identity obtained by a search using the NEEDLE program (Journal of Molecular Biology, 1970, vol. 48, p. 443-453) with the default parameters. The parameters are as follows.

Gap penalty=10 Extend penalty=0.5

Matrix=EBLOSUM62

[0055] The vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit has (have) the oncolytic activity. Examples of methods for evaluating whether or not a test virus has the oncolytic activity include a method for evaluating decrease of the survival rate of cancer cells by the addition of the virus. Examples of cancer cells to be used for the evaluation include the malignant melanoma cell RPMI-7951 (for example, ATCC HTB-66), the lung adenocarcinoma HCC4006 (for example, ATCC CRL-2871), the lung carcinoma A549 (for example, ATCC CCL-185), the small cell lung cancer cell DMS 53 (for example, ATCC CRL-2062), the lung squamous cell carcinoma NCI-H226 (for example, ATCC CRL-5826), the kidney cancer cell Caki-1 (for example, ATCC HTB-46), the bladder cancer cell 647-V (for example, DSMZ ACC 414), the head and neck cancer cell Detroit 562 (for example, ATCC CCL-138), the breast cancer cell JIMT-1 (for example, DSMZ ACC 589), the breast cancer cell MDA-MB-231 (for example, ATCC HTB-26), the esophageal cancer cell OE33 (for example, ECACC 96070808), the glioblastoma U-87MG (for example, ECACC 89081402), the neuroblastoma GOTO (for example, JCRB JCRB0612), the myeloma RPMI 8226 (for example, ATCC CCL-155), the ovarian cancer cell SK-OV-3 (for example, ATCC HTB-77), the ovarian cancer cell OVMANA (for example, JCRB JCRB1045), the colon cancer cell RKO (for example, ATCC CRL-2577), the colorectal carcinoma HCT 116 (for example, ATCC CCL-247), the pancreatic cancer cell BxPC-3 (for example, ATCC CRL-1687), the prostate cancer cell LNCaP clone FGC (for example, ATCC CRL-1740), the hepatocellular carcinoma JHH-4 (for example, JCRB JCRB0435), the mesothelioma NCI-H28 (for example, ATCC CRL-5820), the cervical cancer cell SiHa (for example, ATCC HTB-35), and the gastric cancer cell Kato III (for example, RIKEN BRC RCB2088). Specific examples of methods for the evaluation that can be used include the method described in Example 3 below.

[0056] The vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit produce(s) the IL-7 and/or IL-12 polypeptide(s). Use of the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit markedly increases the antitumor effect by producing the IL-7 and IL-12 polypeptides. The production of IL-7 and IL-12 can be confirmed using a method known in the field, for example, after culturing, with cancer cells, vaccinia virus in which polynucleotides encoding the IL-7 and IL-12 polypeptides are introduced followed by measuring the IL-7 and IL-12 concentrations in the culture supernatant, by immunostaining of cells, by conducting Western blot analysis of the cell lysate, or by measuring the concentrations of IL-7 and IL-12 in the cell lysate. The concentrations of IL-7 and IL-12 can be measured using, for example, Human IL-7 ELISA kit (RayBiotech, Inc.) and Human IL-12 p70 DuoSet ELISA (R&D Systems, Inc.), respectively. Specific examples of methods for evaluating polypeptide concentrations in the culture supernatant or cell lysate that can be used include the method described in Example 4 below. The immunostaining of cells or the Western blot analysis of the cell lysate can be conducted using commercially available antibodies against IL-7 and IL-12.

[0057] The polynucleotides encoding IL-7 and IL-12 can be synthesized based on publicly available sequence information using a method of polynucleotide synthesis known in the field. Moreover, once the polynucleotides are obtained; then modified forms having the function of each polypeptide can be generated by introducing mutation into a predetermined site using a method known by those skilled in the art, such as site-directed mutagenesis (Current Protocols in Molecular Biology edition, 1987, John Wiley & Sons Sections 8.1-8.5).

[0058] The polynucleotides each encoding IL-7 and IL-12 can be introduced into vaccinia virus by a known technique, such as homologous recombination or site-directed mutagenesis. For example, a plasmid (also referred to as transfer vector plasmid DNA) in which the polynucleotide(s) is (are) introduced into the nucleotide sequence at the site desired to be introduced can be made and introduced into cells infected with vaccinia virus. The region in which the polynucleotides each encoding IL-7 and IL-12, foreign genes, are introduced is preferably a gene region that is inessential for the life cycle of vaccinia virus. For example, in a certain aspect, the region in which IL-7 and/or IL-12 is (are) introduced may be a region within the VGF gene in vaccinia virus deficient in the VGF function, a region within the O1L gene in vaccinia virus deficient in the O1 function, or a region or regions within either or both of the VGF and O1L genes in vaccinia virus deficient in both VGF and O1 functions. In the above, the foreign gene(s) can be introduced so as to be transcribed in the direction same as or opposite to that of the VGF and O1L genes.

[0059] Methods for introducing transfer vector plasmid DNA into cells are not particularly limited, but examples of methods that can be used include the calcium phosphate method and electroporation.

[0060] When introducing the polynucleotides each encoding IL-7 and IL-12, which are foreign genes, a suitable promoter(s) can be operably linked in the upstream of the foreign gene(s). In this way, the foreign gene(s) in the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit can be linked to a promoter that can promote expression in tumor cells. Examples of such a promoter include PSFJ1-10, PSFJ2-16, the p7.5K promoter, the p11K promoter, the T7.10 promoter, the CPX promoter, the HF promoter, the H6 promoter, and the T7 hybrid promoter.

[0061] In one embodiment, the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit has (have) no drug-selection marker gene.

[0062] The vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit may be expressed and/or proliferated by infecting host cells with the vaccinia virus(es) and culturing the infected host cells. Vaccinia virus may be expressed and/or proliferated by a method known in the field. Host cells to be used to express or proliferate the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit are not particularly limited, as long as the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit can be expressed and proliferated. Examples of such host cells include animal cells such as BS-C-1, A549, RK13, HTK-143, Hep-2, MDCK, Vero, HeLa, CV-1, COS, BHK-21, and primary rabbit kidney cells. BS-C-1 (ATCC CCL-26), A549 (ATCC CCL-185), CV-1 (ATCC CCL-70), or RK13 (ATCC CCL-37) may be preferably used. Culture conditions for the host cells, for example, temperature, pH of the medium, and culture time, are selected as appropriate.

[0063] Methods for producing the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, and the vaccinia viruses for the combination kit may comprise the steps of: infecting host cells with the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit; culturing the infected host cells; and expressing the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit; and optionally collecting and preferably purifying the vaccinia virus according to the present invention, the vaccinia virus to be used in combination, or the vaccinia viruses for the combination kit. Methods that can be used for the purification include DNA digestion with Benzonase, sucrose gradient centrifugation, Iodixanol density gradient centrifugation, ultrafiltration, and diafiltration.

<Pharmaceutical Composition According to the Present Invention>

[0064] The pharmaceutical compositions according to the present invention include a pharmaceutical composition comprising the vaccinia virus according to the present invention and a pharmaceutically acceptable excipient. The pharmaceutical compositions according to the present invention also include the pharmaceutical composition to be used in combination according to the present invention. In one embodiment, the pharmaceutical composition to be used in combination according to the present invention comprises a pharmaceutically acceptable excipient.

[0065] The pharmaceutical compositions according to the present invention may be prepared by a method usually used in the field, using an excipient usually used in the field, that is, a pharmaceutical excipient, a pharmaceutical carrier, or the like. Examples of the dosage form of such pharmaceutical compositions include parenteral formulations such as injections and infusions and these can be administered by intravenous administration, subcutaneous administration, intratumoral administration, or the like. In the formulation, excipients, carriers, or additives suitable for these dosages form may be used as long as these are pharmaceutically acceptable.

[0066] The effective dose varies according to the severity of the symptom or the age of the patient, the dosage form of the formulation to be used, or the titer of the virus, but, for example, approximately 10.sup.2-10.sup.10 plaque-forming units (PFU) may be used as an effective dose of a single virus, as a combined effective dose of 2 viruses in a combination kit, or as a combined effective dose of 2 viruses administered in combination. Two viruses in a combination kit may be used, for example, at a dosage ratio of approximately 1:10 to 10:1, approximately 1:5 to 5:1, approximately 1:3 to 3:1, approximately 1:2 to 2:1, or about 1:1.

<Application for Preventing or Treating Cancer>

[0067] The pharmaceutical compositions according to the present invention can be used as a prophylactic or therapeutic agent for cancer, for example, a cancer selected from the group consisting of malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer and gastric cancer.

[0068] The present invention includes a pharmaceutical composition for preventing or treating cancer, for example, a cancer selected from the group consisting of malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer and gastric cancer, the composition comprising the vaccinia virus according to the present invention or the vaccinia virus to be used in combination.

[0069] The present invention includes a combination kit for preventing or treating cancer, for example, a cancer selected from the group consisting of malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer and gastric cancer, the combination kit comprising each of the vaccinia viruses for the combination kit.

[0070] Moreover, the present invention includes a method for preventing or treating cancer, for example, a cancer selected from the group consisting of malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer and gastric cancer, the method comprising the step of administering the vaccinia virus according to the present invention to a subject (for example, a patient) in need of the prevention or treatment of cancer.

[0071] Moreover, the present invention includes a method for preventing or treating cancer, for example, a cancer selected from the group consisting of malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer and gastric cancer, the method comprising the step of administering the following (1) and (2) to a subject (for example, a patient) in need of the prevention or treatment of cancer:

(1) a vaccinia virus comprising a polynucleotide encoding IL-7; and (2) a vaccinia virus comprising a polynucleotide encoding IL-12.

[0072] The two vaccinia viruses may be administered to a subject simultaneously, separately, continuously, or at intervals.

[0073] Moreover, the present invention includes the vaccinia virus according to the present invention, for preventing or treating cancer, for example, a cancer selected from the group consisting of malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer and gastric cancer.

[0074] The present invention includes the vaccinia virus selected from the following (1) or (2), for preventing or treating cancer, for example, a cancer selected from the group consisting of malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer and gastric cancer:

(1) a vaccinia virus comprising a polynucleotide encoding IL-7, for preventing or treating cancer in combination with a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-12; or (2) a vaccinia virus comprising a polynucleotide encoding IL-12, for preventing or treating cancer in combination with a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-7.

[0075] Furthermore, the present invention includes use of the vaccinia virus according to the present invention, for the manufacture of a pharmaceutical composition for preventing or treating cancer, for example, a cancer selected from the group consisting of malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer and gastric cancer.

[0076] The present invention includes use of a vaccinia virus selected from the following (1) or (2), for the manufacture of a pharmaceutical composition for preventing or treating cancer, for example, a cancer selected from the group consisting of malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer and gastric cancer:

(1) use of a vaccinia virus comprising a polynucleotide encoding IL-7, for the manufacture of a pharmaceutical composition for preventing or treating cancer to be used in combination with a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-12; or (2) use of a vaccinia virus comprising a polynucleotide encoding IL-12, for the manufacture of a pharmaceutical composition for preventing or treating cancer to be used in combination with a pharmaceutical composition comprising a vaccinia virus comprising a polynucleotide encoding IL-7.

[0077] Furthermore, the present invention includes use of a vaccinia virus comprising a polynucleotide encoding IL-7 and a vaccinia virus comprising a polynucleotide encoding IL-12, for the manufacture of a combination kit for preventing or treating cancer, for example, a cancer selected from the group consisting of malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer and gastric cancer.

[0078] As used herein, "for preventing" is used synonymously with "for use in preventing" and "for treating" is used synonymously with "for use in treating".

[0079] The pharmaceutical compositions or the combination kit according to the present invention may be used in combination with various therapeutic agents having efficacy for cancer for example, a cancer selected from the group consisting of malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer and gastric cancer. The combination use may be performed by simultaneous administration, or separate administration continuously or at the desired interval. When administered simultaneously, the pharmaceutical compositions according to the present invention may be administered as a combined drug or as formulations formulated separately.

[0080] Cancers that the vaccinia virus according to the present invention, the pharmaceutical compositions according to the present invention, the combination kit according to the present invention, the method for preventing or treating cancer according to the present invention, or use according to the present invention is (are) applied to include metastatic cancers to an organ, for example, a lymph node, liver, or the like, besides the primary lesion.

[0081] The present invention has been generally described, but specific Examples for reference to get further understanding of the present invention are provided below. These Examples are for the illustration purpose, but not intended to limit the present invention.

EXAMPLES

[0082] Experiments with a commercially available kit or a reagent were conducted according to attached protocols unless otherwise specified.

Example 1: Construction of Transfer Vector Plasmid DNA

[0083] Transfer vector plasmid DNAs to be used for generating recombinant vaccinia viruses by homologous recombination were prepared as follows.

(1) Construction of pTN-VGF-P-DsRed Transfer Vector Plasmid DNA

[0084] The pUC19-VGF vector was prepared according to WO 2015/076422. More specifically, genomic DNA (Accession No. AY678277.1) of the strain LC16mO was used as template and the pUC19 vector (product cord: 54357) from Invitrogen was used for the preparation of the pUC19-VGF vector. The prepared pUC19-VGF vector was digested with the restriction enzyme AccI and then the ends were blunted. The transfer vector plasmid DNA was constructed by inserting a DNA fragment (SEQ ID NO: 22) containing the p7.5k promoter and a DsRed fragment in this cleavage site. The constructed plasmid DNA was named pTN-VGF-P-DsRed.

(2) Construction of pTN-VGF-SP-IL12 and pTN-VGF-SP-IL7 Transfer Vector Plasmid DNAs

[0085] A BFP gene region was amplified with two primers (SEQ ID NO: 1 and SEQ ID NO: 2) using DNA of the pTagBFP-N vector (FP172, Evrogen) as template. The PCR product was digested with the restriction enzymes SfiI and EcoRI and cloned into the same restriction enzyme sites in the pTK-SP-LG vector (WO 2015/076422 with the proviso that genomic DNA (Accession No. AY678277.1) of the strain LC16mO was used as template and the pUC19 vector (product cord: 54357) from Invitrogen was used; and, for the pVNC110-Luc/IRES/EGFP plasmid, pVNC110-Luc/IRES/EGFP described in WO 2011/125469 was used.) to construct pTK-SP-BFP in which BFP is linked to a synthetic vaccinia virus promoter (Journal of Virological Methods, 1997, vol. 66, p. 135-138). Next, pTK-SP-BFP was digested with the restriction enzymes SphI and EcoRI and the ends were blunted. The resulting DNA fragment was cloned into the pUC19-VGF vector at a site generated by digesting the plasmid with the restriction enzyme AccI and blunting the ends to construct pTN-VGF-SP-BFP (FIG. 1). Next, a polynucleotide encoding human IL-12 (a polynucleotide containing the human IL-12 subunit p40, an internal ribosomal entry site, and the human IL-12 subunit .alpha.; SEQ ID NO: 7) and a polynucleotide (SEQ ID NO: 8) encoding human IL-7 (each polynucleotide contains the restriction enzyme site accggtcgccacc (SEQ ID NO: 16) at the 5' side and the restriction enzyme site gctagcgaattc (SEQ ID NO: 17) at the 3'side.) were digested with the restriction enzymes AgeI and NheI. Each of the polynucleotide fragments was cloned into the same restriction enzyme site in pTN-VGF-SP-BFP to construct the transfer vector plasmid DNA. The constructed plasmid DNAs were named pTN-VGF-SP-IL12 and pTN-VGF-SP-IL7, respectively.

(3) Construction of pTN-O1L-SP-BFP, pTN-O1L-SP-LacZ, pTN-O1L-SP-IL12, and pTN-O1L-SP-IL7 Transfer Vector Plasmid Dnas

[0086] In the same way as (2) above, pTK-SP-BFP was digested with the restriction enzymes SphI and EcoRI and the DNA fragment obtained by blunting the ends was cloned into the pUC19-O1L vector (WO 2015/076422 with the proviso that, like the preparation of the pUC19-VGF vector, genomic DNA (Accession No. AY678277.1) of the strain LC16mO was used as template and the pUC19 vector (product cord: 54357) from Invitrogen was used; and the O1L gene region was inserted into the XbaI site in the pUC19 vector.) at a site generated by digesting the plasmid with the restriction enzyme XbaI and blunting the ends to construct the transfer vector plasmid DNA (FIG. 1). The prepared plasmid DNA was named pTN-O1L-SP-BFP. Next, a polynucleotide (SEQ ID NO: 9) containing the Escherichia coli LacZ gene with codons optimized for human, a polynucleotide (SEQ ID NO: 7) encoding human IL-12, and a polynucleotide (SEQ ID NO: 8) encoding human IL-7 were digested with the restriction enzymes AgeI and NheI. Each of the polynucleotide fragments encoding LacZ, IL-12, or IL-7 was cloned into the same restriction enzyme sites (the AgeI and NheI sites) in the pTN-O1L-SP-BFP vector to construct the transfer vector plasmid DNA. The constructed plasmid DNAs were named pTN-O1L-SP-LacZ, pTN-O1L-SP-IL12, and pTN-O1L-SP-IL7, respectively.

(4) Construction of pTN-DsRed (B5R-) and pTN-B5R.DELTA.1-4 Transfer Vector Plasmid DNAs

[0087] The B4R gene region was amplified with two primers (SEQ ID NO: 3 and SEQ ID NO: 4) using DNA of pB5R (WO 2011/125469, with the proviso that genomic DNA (Accession No. AY678277.1) of the strain LC16mO was used as template) as template. Moreover, the DsRed gene region was amplified with two primers (SEQ ID NO: 5 and SEQ ID NO: 6) using DNA of pDsRed-Express-N1 (Clontech Laboratories, Inc.) as template. The former PCR product was digested with the restriction enzymes NotI and FspI and the latter PCR product was digested with the restriction enzymes FspI and MfeI. These two DNA fragments were cloned into pB5R digested with the restriction enzymes NotI and MfeI to construct the transfer vector plasmid DNA. The prepared plasmid DNA was named pTN-DsRed (B5R-). Meanwhile, pB5R was digested with the restriction enzymes NotI and NspI or the restriction enzymes NspI and SacI. These two DNA fragments were cloned into pB5R digested with the restriction enzymes NotI and SacI to construct the transfer vector plasmid DNA. The prepared plasmid DNA was named pTN-B5R.DELTA.1-4. pTN-B5R.DELTA.1-4 encodes the B5R protein with the deletion of four SCR domains. The amino acid sequence thereof is the sequence set forth in SEQ ID NO: 18.

Example 2: Construction of Genetically Engineered Vaccinia Virus

[0088] A recombinant vaccinia virus (referred to as LC16mO VGF-SP-LucGFP/O1L-p7.5-DsRed) deficient in the functions of VGF and O1L was prepared from the vaccinia virus strain LC16mO. This recombinant vaccinia virus was sequenced with a next-generation sequencer PacBio RSII (Pacific Biosciences of California, Inc.) and the virus genome was reconstituted from the obtained sequence information using the Sprai [BMC GENOMICS. 2014 Aug. 21, 15:699.] software to determine the nucleotide sequence, which is the nucleotide sequence set forth in SEQ ID NO: 21. Moreover, loop sequences were added to both ends of the nucleotide sequence and the loop sequences at both ends were the nucleotide sequences set forth in SEQ ID NOs: 19 or 20.

[0089] (1) The recombinant vaccinia viruses having the virus genome illustrated in FIG. 2 were collected. The virus collecting procedure is specifically described below. CV1 cells (ATCC CCL-70) or RK13 cells (ATCC CCL-37) cultured to 80% confluent in 6 well dishes were infected with LC16mO VGF-SP-LucGFP/O1L-p7.5-DsRed at a Multiplicity of infection (MOI)=0.02-0.1 and the virus was allowed to be adsorbed at room temperature for 1 hour. pTN-O1L-SP-BFP constructed in Example 1 (3) was mixed with FuGENE.RTM. HD Transfection Reagent (Roche), added to cells according to the manual to be incorporated into the cells and the cells were cultured at 5% CO.sub.2 and 37.degree. C. for 2-5 days. The cells were freeze-thawed, sonicated, and diluted with Opti-MEM (Invitrogen) so as to obtain single plaques by the following operation. 100 .mu.L of the resulting diluted fluid was added to inoculate BS-C-1 cells (ATCC CCL-26) or RK13 cells cultured to sub-confluent in 6 well dishes. 2 mL of the Eagle MEM medium (NISSUI, 05900) containing 0.8% methylcellulose (Wako Pure Chemical Industries, Ltd., 136-02155), 5% fetal bovine serum, 0.225% sodium bicarbonate (Wako Pure Chemical Industries, Ltd., 195-16411), and GlutaMAX.TM. Supplement I (GIBCO, 35050-061) was added and the cells were cultured at 5% CO.sub.2 and 37.degree. C. for 2-5 days. The medium was removed and plaques, as indicated by the BFP expression, were scraped off with the pointing end of a tip to be suspended into Opti-MEM. This operation was repeated three times or more with BS-C-1 or RK13 cells to purify plaques and collect the virus plaques (In this Example, the procedure up to this point is hereinafter referred to as the "collecting".). The plaques were suspended into Opti-MEM and sonicated. Genomic DNA was extracted from 200 .mu.L of the sonicated solution using High Pure Viral Nucleic Acid Kit (Roche) according to the manual and screened by PCR. PCR was performed for VGF with the two primers (SEQ ID NO: 10 and SEQ ID NO; 11), for O1L with the two primers (SEQ ID NO: 12 and SEQ ID NO: 13), and for B5R with the two primers (SEQ ID NO: 14 and SEQ ID: NO 15). Among the clones from which an expected size of PCR product was detected, a virus clone for which the correct nucleotide sequence of the PCR product was confirmed by direct sequencing (referred to as LC16mO VGF-SP-LucGFP/O1L-SP-BFP. FIG. 2) was selected and proliferated with A549 (ATCC CCL-185) or RK13 cells and then the virus titer was measured with RK13 cells. Using LC16mO VGF-SP-LucGFP/O1L-SP-BFP and pTN-DsRed (B5R-) prepared in Example 1 (4), the recombinant virus, as indicated by the DsRed expression instead of the BFP expression, was collected in a way same as that described above. The virus was named LC16mO .DELTA.-DsRed VGF-SP-LucGFP/O1L-SP-BFP (FIG. 2).

[0090] (2) A recombinant virus having the deletion of the 4 SCR domains in the B5R protein was collected. Specifically, using LC16mO .DELTA.-DsRed VGF-SP-LucGFP/O1L-SP-BFP prepared in Example 2 (1) and pTN-B5R.DELTA.1-4 constructed in Example 1 (4), the recombinant virus, as indicated by the disappearance of DsRed expression instead of the BFP expression, was collected in a way same as that in Example 2 (1). The virus was named LC16mO .DELTA.SCR VGF-SP-LucGFP/O1L-SP-BFP (FIG. 2). Moreover, using the prepared LC16mO .DELTA.SCR VGF-SP-LucGFP/O1L-SP-BFP and pTN-VGF-P-DsRed constructed in Example 1 (1), the recombinant virus, as indicated by the DsRed expression instead of the BFP expression, was collected in a way same as that in Example 2 (1). The virus is named LC16mO .DELTA.SCR VGF-p7.5-DsRed/O1L-SP-BFP (FIG. 2). Next, using the obtained LC16mO .DELTA.SCR VGF-p7.5-DsRed/O1L-SP-BFP and pTN-O1L-SP-LacZ constructed in Example 1 (3), the recombinant virus, as indicated by the disappearance of BFP expression instead of the BFP expression, was collected in a way same as that in Example 2 (1). The virus was named LC16mO .DELTA.SCR VGF-p7.5-DsRed/O1L-SP-LacZ (FIG. 2).

[0091] (3) The SCR region-deleted recombinant vaccinia viruses having the virus genome illustrated in FIG. 3 and expressing a therapeutic gene and a marker gene were collected. Specifically, using each of LC16mO .DELTA.SCR VGF-p7.5-DsRed/O1L-SP-LacZ prepared in Example 2 (2) and the transfer vector plasmid DNAs (pTN-VGF-SP-IL12 and pTN-VGF-SP-IL7) constructed in Example 1 (2), each of the recombinant viruses, as indicated by the disappearance of DsRed expression instead of the BFP expression, was collected in a way same as that in Example 2 (1). The viruses were named LC16mO .DELTA.SCR VGF-SP-IL12/O1L-SP-LacZ (hereinafter, referred to as the "hIL12-carrying vaccinia virus".) and LC16mO .DELTA.SCR VGF-SP-IL7/O1L-SP-LacZ (hereinafter, referred to as the "hIL7-carrying vaccinia virus".) (FIG. 3). For purification, A549 or RK13 cells were infected with each of the recombinant viruses. The cells were cultured at 5% CO.sub.2 and 37.degree. C. for 2-5 days and then the infected cells were harvested. The cells were freeze-thawed and sonicated. The viruses were purified by density gradient centrifugation using OptiPrep (Axis-Shield Diagnostics Ltd.). The virus titer of each virus was measured with RK13 cells.

[0092] (4) The SCR domain-deleted recombinant vaccinia virus having the virus genome illustrated in FIG. 4 and expressing a polynucleotide encoding human IL-7 and a polynucleotide encoding human IL-12 was collected.

[0093] (4-1) Specifically, using LC16mO .DELTA.SCR VGF-p7.5-DsRed/O1L-SP-BFP prepared in Example 2 (2) and the transfer vector plasmid DNA pTN-VGF-SP-IL12 constructed in Example 1 (2), each of the recombinant viruses, as indicated by the disappearance of DsRed expression instead of the BFP expression, was collected in a way same as that in Example 2 (1). The virus was named LC16mO .DELTA.SCR VGF-SP-IL12/O1L-SP-BFP.

[0094] (4-2) Next, using LC16mO .DELTA.SCR VGF-SP-IL12/O1L-SP-BFP prepared in Example 2 (4-1) and the transfer vector plasmid DNA pTN-O1L-SP-IL7 constructed in Example 1 (3), each of the recombinant viruses, as indicated by the disappearance of BFP expression instead of the BFP expression, was collected in a way same as that in Example 2 (1). The virus was named LC16mO .DELTA.SCR VGF-SP-IL12/O1L-SP-IL7 (hereinafter, in Examples below, also referred to as the "hIL12 and hIL7-carrying vaccinia virus".) (FIG. 4). Each recombinant virus was purified by the method in Example 2 (3) and then the virus titer of each virus was measured with RK13 cells.

Example 3: Oncolytic Property of Genetically Engineered Vaccinia Virus

[0095] The ability of the hIL12 and hIL7-carrying vaccinia virus prepared in Example 2 to lyse various human cancer cells (ability to kill cells) was evaluated. Moreover, the ability of a combined mixture of 2 viruses, the hIL12-carrying vaccinia virus and the hIL7-carrying vaccinia virus prepared in Example 2, to lyse various human cancer cells was similarly evaluated.

[0096] Specifically, 100 .mu.L each of the cells suspended at 1.times.10.sup.4 cells/mL in a medium (a medium described below containing 10% fetal bovine serum (GE Healthcare) and 1% penicillin-streptomycin (Life Technologies)) was first added into 96 well plates (AGC TECHNO GLASS CO., LTD.). After culturing overnight, 1) the hIL12 and hIL7-carrying vaccinia virus and 2) a mixture combining 1:1 concentrations of the hIL12-carrying vaccinia virus and the hIL7-carrying vaccinia virus (hereinafter, referred to as the "mixture of hIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus") were each diluted with Opti-MEM (Life Technologies) at 5.times.10.sup.4 PFU/mL, 5.times.10.sup.5 PFU/mL, and 5.times.10.sup.6 PFU/mL, respectively. 20 .mu.L each of the virus solutions was added to each well to infect cells at MOI=1.0, 10, or 100. As control, wells with no cells and wells to which Opti-MEM was added instead of virus (MOI=0) were prepared. The cells were then cultured for 5 days in a CO.sub.2 incubator set to a CO.sub.2 concentration of 5% and at 37.degree. C. The cell survival rate on Day 5 was measured with CellTiter-Glo Luminescent Cell Viability Assay (Promega KK.). Specifically, according to the protocol of the assay kit, 100 .mu.L each of CellTiter-Glo Reagent was added to each well and left to stand for 30 minute, the total amount was then transferred into 96 well black plates (Corning Incorporated), and the strength of luminescence in each well was measured with EnSpire (PerkinElmer Inc.). For the calculation of the cell survival rate in each well, the value of wells in which no cells have seeded was defined as 0% survival and the value of wells in which cells have seeded and no virus was added was defined as 100% survival.

[0097] The evaluated cells were the malignant melanoma cell RPMI-7951 (ATCC HTB-66), the lung adenocarcinoma HCC4006 (ATCC CRL-2871), the lung carcinoma A549 (ATCC CCL-185), the small cell lung cancer cell DMS 53, the lung squamous cell carcinoma NCI-H226 (ATCC CRL-5826), the kidney cancer cell Caki-1 (ATCC HTB-46), the bladder cancer cell 647-V (DSMZ ACC 414), the head and neck cancer cell Detroit 562 (ATCC CCL-138), the breast cancer cell JIMT-1 (DSMZ ACC 589), the breast cancer cell MDA-MB-231 (ATCC HTB-26), the esophageal cancer cell OE33 (ECACC 96070808), the glioblastoma U-87MG (ECACC 89081402), the neuroblastoma GOTO (JCRB JCRB0612), the myeloma RPMI 8226 (ATCC CCL-155), the ovarian cancer cell SK-OV-3 (ATCC HTB-77), the ovarian cancer cell OVMANA (JCRB JCRB1045), the colon cancer cell RKO (ATCC CRL-2577), the colorectal carcinoma HCT 116, the pancreatic cancer cell BxPC-3 (ATCC CRL-1687), the prostate cancer cell LNCaP clone FGC (ATCC CRL-1740), the hepatocellular carcinoma JHH-4 (JCRB JCRB0435), the mesothelioma NCI-H28 (ATCC CRL-5820), the cervical cancer cell SiHa (ATCC HTB-35) and the gastric cancer cell Kato III (RIKEN BRC RCB2088).

[0098] The media used were RPMI1640 medium (Sigma-Aldrich Co. LLC., R8758) for RPMI-7951, HCC4006, DMS 53, NCI-H226, Caki-1, 647-V, Detroit 562, JIMT-1, OE33, U-87MG, GOTO, RPMI8226, SK-OV-3, OVMANA, RKO, HCT 116, BxPC-3, LNCaP clone FGC, JHH-4, NCI-H28, and Kato III, DMEM medium (Sigma-Aldrich Co. LLC., D6429) for A549 and MDA-MB-231, and EMEM medium (ATCC 30-2003) for SiHa. The results were as illustrated in FIGS. 5-1 to 5-4. In relation with this, the effects of the hIL12 and hIL7-carrying vaccinia virus were illustrated separately in FIGS. 5-1 and 5-2 and the effects of the mixture of hIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus were illustrated separately in FIGS. 5-3 and 5-4.

[0099] As a result, the hIL12 and hIL7-carrying vaccinia virus was shown to have the ability to kill cells in all examined human cancer cells (FIGS. 5-1 and 5-2). Moreover, the mixture of hIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus was also shown to have the ability to kill cells in all examined human cancer cells (FIGS. 5-3 and 5-4). In FIGS. 5-1 to 5-4, the oncolytic properties at MOI=0, 1, 10, and 100 are shown from the left in this order for each cell line.

Example 4: Protein Production from Cancer Cells Infected with Genetically Engineered Vaccinia Virus

[0100] When cancer cells were infected with the hIL12 and hIL7-carrying vaccinia virus, the concentrations of the human IL-7 protein and the human IL-12 protein produced by cancer cells were measured. Furthermore, the concentrations of the human IL-7 protein and the human IL-12 protein produced by cancer cells when cancer cells were infected with the mixture of hIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus were similarly measured.

[0101] The measurement of the human IL-7 protein was conducted as follows. Specifically, first, 100 .mu.L of SK-OV-3 ovarian cancer cells suspended at 1.times.10.sup.4 cells/mL in RPMI1640 medium containing 10% fetal bovine serum and the 1% penicillin-streptomycin was seeded into 96 well plates. After culturing overnight, 1) the hIL12 and hIL7-carrying vaccinia virus or 2) the mixture of hIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus was prepared in Opti-MEM and 20 .mu.L each was added to infect the cells at MOI=1.0. The cells were then cultured for 24 hours in a CO.sub.2 incubator set at a CO.sub.2 concentration of 5% and 37.degree. C. and the culture supernatant was collected. The concentration of the protein contained in the culture supernatant was measured with the ELISA kit listed in Table 1 and EnSpire.

[0102] The measurement of the human IL-12 protein was conducted as follows. Specifically, first, 100 .mu.L of SK-OV-3 ovarian cancer cells suspended at 1.times.10.sup.5 cells/mL in RPMI1640 medium containing 10% fetal bovine serum and the 1% penicillin-streptomycin was seeded into 96 well plates. After culturing overnight, 1) the hIL12 and hIL7-carrying vaccinia virus or 2) the mixture of hIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus was prepared in Opti-MEM and 20 .mu.L each was added to infect the cells at MOI=1.0. The cells were then cultured for 48 hours in a CO.sub.2 incubator set at a CO.sub.2 concentration of 5% and 37.degree. C. and the culture supernatant was collected. The concentration of the protein contained in the culture supernatant was measured with the ELISA kit listed in Table 1 and EnSpire.

TABLE-US-00001 TABLE 1 ELISA kit used in Example 4 Protein ELISA kit Provider Human IL-7 Human IL-7 ELISA kit RayBiotech, Inc. Human IL-12 Human IL-12 p70 DuoSet R&D Systems, Inc. ELISA

[0103] As a result, it was shown that the human IL-12 protein and the human IL-7 protein were produced from the cells to which the hIL12 and hIL7-carrying vaccinia virus was added and the cells to which the mixture of hIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus was added (Tables 2-1 and 2-2).

TABLE-US-00002 TABLE 2-1 Concentration of human IL-12 protein in culture supernatant Human IL-12 protein Genetically engineered vaccinia virus concentration (ng/mL) hIL12 and hIL7-carrying vaccinia virus 31.45 Mixture of hIL12-carrying vaccinia virus 17.74 and hIL7-carrying vaccinia virus

TABLE-US-00003 TABLE 2-2 Concentration of human IL-7 protein in culture supernatant Human IL-7 protein Genetically engineered vaccinia virus concentration (ng/mL) hIL12 and hIL7-carrying vaccinia virus 0.86 Mixture of hIL12-carrying vaccinia virus 0.60 and hIL7-carrying vaccinia virus

Example 5: Construction of Transfer Vector Plasmid DNA Carrying Polynucleotide Encoding Murine IL-12 and Construction of Recombinant Vaccinia Virus Carrying Polynucleotide Encoding Murine IL-12

[0104] (1) The transfer vector plasmid DNA pTN-VGF-SP-mIL12 was constructed according to the method described in Example 1 (2). Instead of the polynucleotide (SEQ ID NO: 7) encoding human IL-12 in the method described in Example 1 (2), a polynucleotide encoding murine IL-12 (a polynucleotide containing the murine IL-12 subunit p40, an internal ribosomal entry site, and the murine IL-12 subunit .alpha.. SEQ ID NO: 23) was used and this polynucleotide fragment was cloned into pTN-VGF-SP-BFP.

[0105] (2) The transfer vector plasmid DNA pTN-O1L-SP-Luc2 was constructed according to the method described in Example 1 (3). Instead of the polynucleotide (SEQ ID NO: 9) containing the Escherichia coli LacZ gene in the method described in Example 1 (3), a polynucleotide (100-1752 in Accession No. DQ188840) encoding the luciferase Luc2 gene was used and this polynucleotide fragment was cloned into pTN-O1L-SP-BFP.

[0106] (3) The recombinant virus was collected according to the method in Example 2 (2). In the method in Example 2 (2), LC16mO .DELTA.SCR VGF-p7.5-DsRed/O1L-SP-BFP and pTN-O1L-SP-Luc2 prepared in Example 5 (2) instead of pTN-O1L-SP-LacZ were used. The virus was named LC16mO .DELTA.SCR VGF-p7.5-DsRed/O1L-SP-Luc2 (hereinafter, this virus is also referred to as the "control vaccinia virus".).

[0107] (4) The recombinant virus was collected according to the method in Example 2 (3). Instead of LC16mO .DELTA.SCR VGF-p7.5-DsRed/O1L-SP-LacZ and pTN-VGF-SP-IL12 in the method in Example 2 (3), respectively, LC16mO .DELTA.SCR VGF-p7.5-DsRed/O1L-SP-Luc2 prepared in Example 5 (3) and pTN-VGF-SP-mIL12 prepared in Example 5 (1) were used. The virus was named LC16mO .DELTA.SCR VGF-SP-mIL12/O1L-SP-Luc2 (hereinafter, also referred to as the "mIL12-carrying vaccinia virus".).

[0108] (5) The recombinant virus was collected according to the method in Example 2 (4-1). LC16mO .DELTA.SCR VGF-p7.5-DsRed/O1L-SP-BFP and pTN-VGF-SP-mIL12 prepared in Example 5 (1) instead of pTN-VGF-SP-IL12 in the method in Example 2 (4-1) were used. The virus was named LC16mO .DELTA.SCR VGF-SP-mIL12/O1L-SP-BFP.

[0109] Furthermore, the recombinant virus was collected according to the method in Example 2 (4-2). Instead of LC16mO .DELTA.SCR VGF-SP-IL12/O1L-SP-BFP in the method in Example 2 (4-2), LC16mO .DELTA.SCR VGF-SP-mIL12/O1L-SP-BFP prepared as described above and pTN-O1L-SP-IL7 were used. The virus was named LC16mO .DELTA.SCR VGF-SP-mIL12/O1L-SP-IL7 (hereinafter, also referred to as the "mIL12 and hIL7-carrying vaccinia virus".).

Example 6: Antitumor Effect of Genetically Engineered Vaccinia Virus in Cancer-Bearing Humanized Mouse

[0110] The in vivo antitumor effect of the hIL12 and hIL7-carrying vaccinia virus was evaluated using humanized mice (mice in which the immune system is replaced with human immune cells by introducing human hematopoietic stem cells into a severely immunodeficient mouse) into which human cancer cells are transplanted.

[0111] Specifically, in order to generate humanized mice, 3.times.10.sup.4 hematopoietic stem cells (Lonza) derived from human umbilical cord blood were first introduced by injecting via a tail vein into NOG mice (NOD/Shi-scidlL-2RyKO Jic, female, 6 week-old, CLEA Japan, Inc.) irradiated with X-ray at a strength of 2.0 grays using an X-ray irradiation apparatus. 13 weeks after the introduction, 100 .mu.L of the human lung cancer cell NCI-H1373 (ATCC CRL-5866) suspended at 3.times.10.sup.7 cells/mL in PBS was transplanted by injecting the cells subcutaneously in the right back side of the mice. The tumor diameter was measured with a caliper after cancer cell transplantation and the mice were assigned to groups so that the mean tumor volumes of the groups (minor axis mm.times.minor axis mm.times.major axis mm.times.0.52) will become 37 mm.sup.3 to 47 mm.sup.3. On the same day, 20 .mu.L of the hIL12 and hIL7-carrying vaccinia virus diluted to a concentration of 1.0.times.10.sup.8 PFU/mL in PBS was injected into tumor (referred to as the "hIL12 and hIL7-carrying VV treated group" in the Table). 20 .mu.L of PBS was administered into tumor in a group, which was referred to as the vehicle (PBS) treated group. The tumor diameter of each mouse was measured with a caliper every 2-4 days, the tumor volume was calculated based on the formula above, and the percent (%) change in tumor volume on the 14th day after the virus administration was calculated by the following formula for each individual (n=7-8):

Percent (%) change in tumor volume on 14th day after virus administration=100(%).times.tumor volume (mm.sup.3) on 14th day after virus administration/tumor volume (mm.sup.3) on day of virus administration.

[0112] The tumor regression effect was determined to be positive when the mean percent (%) change in tumor volume on the 14th day after the virus administration of each group was less than 100 and a significant difference was observed (the significant difference was defined when p value <0.05) between the tumor volume on the 14th day after the virus administration and the tumor volume on the day of the virus administration in each group when tested by the paired t-test.

[0113] In this Example, the control vaccinia virus (2.times.10.sup.6 PFU/individual), the hIL12-carrying vaccinia virus (2.times.10.sup.6 PFU/individual), or the hIL7-carrying vaccinia virus (2.times.10.sup.6 PFU/individual) (referred to as the "control VV treated group", the "hIL12-carrying VV treated group", and the "hIL7-carrying VV treated group" in the Table.) were used with the same injection volume (20 .mu.L) and the same dilution solution (PBS) as a virus compared with the hIL12 and hIL7-carrying vaccinia virus (2.times.10.sup.6 PFU/individual).

[0114] As a result, the hIL12 and hIL7-carrying vaccinia virus treated group exhibited a mean percent change in tumor volume on the 14th day after the virus administration of less than 100%. Furthermore, there was a significant difference observed between the tumor volume on the 14 days after the virus administration and the tumor volume on the day of virus administration examined by the paired t-test and therefore the tumor regression effect was determined to be positive (Table 3). Thus, the administration of the hIL12 and hIL7-carrying vaccinia virus was shown to have the tumor regression effect. On the other hand, the tumor regression effect was not confirmed in the group receiving either of the hIL12-carrying vaccinia virus or the hIL7-carrying vaccinia virus (Table 3).

TABLE-US-00004 TABLE 3 Percent (%) change in tumor volume in cancer-bearing humanized mouse with the hIL12 and hIL7-carrying vaccinia virus p value (tumor volume Percent (%) on 14th day after change in virus administration tumor volume on and tumor volume 14th day after on day of virus administration administration were Mean +/- examined by the Experimental group n standard error paired t-test) Vehicle (PBS) treated 7 653 .+-. 43 <0.05 group Control VV treated group 7 187 .+-. 39 0.09 hIL7-carrying VV treated 8 199 .+-. 33 <0.05 group hIL12-carrying VV 8 140 .+-. 29 0.40 treated group hIL12 and hIL7-carrying 8 61 .+-. 6 <0.05 VV treated group

Example 7: Complete Remission-Inducing Effect of Genetically Engineered Vaccinia Virus in Syngeneic Cancer-Bearing Mouse Models

[0115] (1) Effect of mIL12 and hIL7-Carrying Vaccinia Virus

[0116] The complete remission-inducing effect of the mIL12 and hIL7-carrying vaccinia virus in vivo was evaluated using mice subcutaneously transplanted with syngeneic murine cancer cell line (syngeneic cancer-bearing mice). Since human IL-12 is known to have no effect on murine immune cells, a genetically engineered vaccinia virus carrying a polynucleotide encoding murine IL-12 instead of the polynucleotide encoding human IL-12 (prepared in Example 5) was used.

[0117] Specifically, 50 .mu.L of the murine lung cancer cell LL/2 (LLC1) (ATCC CRL-1642) (hereinafter referred to as LLC1) prepared at 4.times.10.sup.6 cells/mL in PBS was first subcutaneously transplanted in the right flank of C57BL/6J mice (male, 5-7 week-old, CHARLES RIVER LABORATORIES JAPAN, INC.). The tumor volume was calculated in a way same as that in Example 6 and mice were assigned to groups so that the mean tumor volume of each group will become 50 mm.sup.3 to 60 mm.sup.3. On the next day, 30 .mu.L of the mIL12 and hIL7-carrying vaccinia virus diluted to a concentration of 6.7.times.10.sup.8 PFU/mL in PBS was intratumorally injected in 12 mice (2.times.10.sup.7 PFU, referred to as the "mIL12 and hIL7-carrying VV treated group" in the Table.). Similar intratumoral injection of the virus was conducted 2 days and 4 days after the first administration. 30 .mu.L of PBS instead of the virus was intratumorally administered in a group, which was referred to as the vehicle (PBS) treated group.

[0118] The tumor diameter was measured with a caliper twice a week and the tumor volume was calculated. Absence of tumor observed by palpation on 27th day after the first administration of the virus was defined as complete remission and the number of individuals achieved complete remission was counted. Groups reached a mean tumor volume above 1,700 mm.sup.3 during the test period were euthanized from the viewpoint of animal ethic. In this example, the control vaccinia virus, the mIL12-carrying vaccinia virus, or the hIL7-carrying vaccinia virus (each 2.times.10.sup.7 PFU/dose, three doses) (respectively referred to as the "control VV treated group", the "mIL12-carrying VV treated group", and the "hIL7-carrying VV treated group" in the Table.) was used with the same injection volume (30 .mu.L per dose) and the same dilution solution (PBS) as a virus compared with the mIL12 and hIL7-carrying vaccinia virus (2.times.10.sup.7 PFU/dose, three doses).

[0119] As a result, three individuals finally achieved complete remission in the mIL12 and hIL7-carrying vaccinia virus treated group. On the other hand, no individual achieved complete remission in the group receiving the comparison virus (Table 4-1). Thus, the administration of the mIL12 and hIL7-carrying vaccinia virus was shown to have a higher complete remission-inducing effect in comparison with the hIL7-carrying vaccinia virus or the mIL12-carrying vaccinia virus in syngeneic cancer-bearing mouse models.

TABLE-US-00005 TABLE 4-1 The number of mice individual that achieved complete remission by administration of mIL12 and hIL7-carrying vaccinia virus Number of mouse individual achieved complete remission/ Number of mouse Experimental group individual examined Vehicle (PBS) treated group 0/12 Control VV treated group 0/12 hIL7-carrying VV treated group 0/12 mIL12-carrying VV treated group 0/12 mIL12 and hIL7-carrying VV treated 3/12 group

(2) A Mixture of mIL12-Carrying Vaccinia Virus and hIL7-Carrying Vaccinia Virus

[0120] The complete remission-inducing effect of a 1:1 mixture of the mIL12-carrying vaccinia virus and the hIL7-carrying vaccinia virus (hereinafter, referred to as the "mixture of mIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus") in vivo was evaluated using syngeneic cancer-bearing mice.

[0121] Experiment was conducted in the same way as (1), with the proviso that the murine lung cancer cell LLC1 suspended at 8.times.10.sup.6 cells/mL was transplanted. Furthermore, instead of 30 .mu.L (2.times.10.sup.7 PFU) of the mIL12 and hIL7-carrying vaccinia virus diluted to a concentration of 6.7.times.10.sup.8 PFU/mL, 30 .mu.L (each 2.times.10.sup.7 PFU/dose, three doses) of the mixture of mIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus (each virus was diluted to 6.7.times.10.sup.8 PFU/mL in PBS) (referred to as the "treatment group of mixture of mIL12-carrying VV and hIL7-carrying VV" in the Table.) was used. Seven mice (n=7) were used. The control vaccinia virus (4.times.10.sup.7 PFU/dose, three doses), the 1:1 mixture of the mIL12-carrying vaccinia virus and the control vaccinia virus (each 2.times.10.sup.7 PFU/dose, three doses), or the 1:1 mixture of the hIL7-carrying vaccinia virus and the control vaccinia virus (each 2.times.10.sup.7 PFU/dose, three doses) (respectively, referred to as the "control VV treated group", the "treatment group of mixture of mIL12-carrying VV and control VV", and the "treatment group of mixture of hIL7-carrying VV and control VV" in the Table.) was used with an injection volume of 30 .mu.L each as a comparison virus.

[0122] As a result, four individuals in the group receiving the mixture of mIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus achieved complete remission. Only one individual achieved complete remission in the group receiving the mixture of mIL12-carrying vaccinia virus and the control vaccinia virus, while no individual achieved complete remission in the groups receiving other comparison viruses (Table 4-2). Thus, the mixture of mIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus was shown to have higher complete remission-inducing effect in comparison with mixtures containing either of the hIL7-carrying vaccinia virus or the mIL12-carrying vaccinia virus in a syngeneic cancer-bearing mouse model.

TABLE-US-00006 TABLE 4-2 The number of mice individual that achieved complete remission by administration of the mixture of mIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus Number of mouse individual achieved complete remission/ Number of mouse Experimental group individual examined Vehicle (PBS) treated group 0/7 Control VV treated group 0/7 Treatment group of mixture of hIL7-carrying 0/7 VV and control VV Treatment group of mixture of mIL12-carrying 1/7 VV and control VV Treatment group of mixture of mIL12-carrying 4/7 VV and hIL7-carrying VV

Example 8: Acquired Immunity Effect of Genetically Engineered Vaccinia Virus in Syngeneic Cancer-Bearing Mouse Models (Tumor-Rejecting Effect by Acquired Immunity)

[0123] (1) mIL12 and hIL7-Carrying Vaccinia Virus:

[0124] To the mice achieved complete remission as a result of treating with the mIL12 and hIL7-carrying vaccinia virus, the rechallenge experiment of the same cancer cells was conducted to evaluate acquired immunity effect of the virus.

[0125] Specifically, LLC1 cancer-bearing mice were first generated according to Example 7, and the mIL12 and hIL7-carrying vaccinia virus was intratumorally administered in the mice (with the proviso that the intratumoral injection of the virus was also conducted on 1st and 3rd days after the first administration in addition to 2nd and 4th days (total 5 times); referred to as the "mIL12 and hIL7-carrying VV treated group" in the Table.). The complete remission was confirmed on 23th day after the last administration of the virus. Into the individuals that still maintain the complete remission state on 51th day after the last administration and age-matched mice not inoculated with virus (control group), 50 .mu.L of LLC1 cancer cells suspended at 8.times.10.sup.6/mL in PBS was subcutaneously transplanted. The tumor volume was calculated according to Example 6 and the number of individuals that were recognized to have tumor formation by visual observation and palpation on 14th day after the LLC1 transplantation was counted to determine the ratio of the number of mouse individuals having engrafted tumor/the number of mouse individuals in which cancer cells were transplanted. In this Example, the control group and the virus treated group were tested by the Fisher's exact test and the acquired immunity effect was evaluated to be positive when there was a significant difference (less than 5%).

[0126] As a result, subcutaneous tumor was formed in the all cases of 10 individuals in the total 10 individuals in the control group, but 6 individuals in the total 10 individuals in the mIL12 and hIL7-carrying virus treated group had no tumor formation of rechallenged LLC1 cancer cells found in the visual observation and palpation (Table 5-1) (P<0.05, Fisher's exact test). Thus, the acquired immunity effect of the administration of the mIL12 and hIL7-carrying vaccinia virus was confirmed in this Example.

TABLE-US-00007 TABLE 5-1 Result of cancer cell rechallenge test in mice achieved complete remission Number of mouse individual having engrafted tumor/Number of mouse individual in which cancer cells Experimental group were transplanted Control group 10/10 mIL12 and hIL7-carrying VV treated group 4/10

(2) Mixture of mIL12-Carrying Vaccinia Virus and hIL7-Carrying Vaccinia Virus:

[0127] To the mice achieved complete remission as a result of treating with the mixture of mIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus, the rechallenge experiment of the same cancer cells was conducted to evaluate acquired immunity effect of the virus.

[0128] Specifically, the experiment was conducted in the same way as in (1). However, instead of the mice achieved complete remission by the administration of the mIL12 and hIL7-carrying vaccinia virus, the mice achieved complete remission by the administration of the mixture of mIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus according to Example 7 (2) (1st, 3rd, and 5th day after the group assignment, total 3 times) were used (referred to as the "treatment group of mixture of mIL12-carrying VV and hIL7-carrying VV" in the Table.). The further transplantation of the cancer cells was conducted on 74th day after the last administration of the viruses (determination of complete remission was made on 24th day after the last administration).

[0129] As a result, subcutaneous tumor was formed in the all individuals in the total eight individuals in the control group on 14th day after further transplantation of the cancer cells, but eight individuals in the total 10 individuals in the treatment group of mixture of mIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus had no tumor formation of rechallenged LLC1 cancer cells found in the visual observation and palpation (Table 5-2) (P<0.05, Fisher's exact test).

[0130] Thus, the acquired immunity effect of the administration of the mixture of mIL12-carrying vaccinia virus and hIL7-carrying vaccinia virus was confirmed in this Example.

TABLE-US-00008 TABLE 5-2 Result of cancer cell rechallenge test in mice achieved complete remission Number of mouse individual having engrafted tumor/Number of mouse individual in which cancer cells Experimental group were transplanted Control group 8/8 Treatment group of mixture 2/10 of mIL12-carrying VV and hIL7-carrying VV

INDUSTRIAL AVAILABILITY

[0131] The vaccinia virus, the pharmaceutical composition, and the combination kit according to the present invention are useful for preventing or treating various cancers.

Free Text of Sequence Listing

[0132] The description of "Artificial Sequence" is stated in the numeric identifier <223> of the sequence listing.

[0133] The nucleotide sequences set forth in SEQ ID NOs: 1-6 and 10-15 are primers.

[0134] The nucleotide sequences set forth in SEQ ID NOs: 7, 8, and 9 are a polynucleotide containing the human IL-12 gene, a polynucleotide containing the human IL-7 gene, and a polynucleotide containing the Escherichia coli LacZ gene, respectively. In SEQ ID NO: 7, the nucleotide sequence of 14-1000 corresponds to the region encoding the p40 subunit of IL-12 and the nucleotide sequence of 1606-2367 corresponds to the region encoding the subunit .alpha. of IL-12.

[0135] The nucleotide sequences set forth in SEQ ID NOs: 16 and 17 are the restriction enzyme sites linked to each of the gene coding regions of SEQ ID NOs: 7-9.

[0136] The amino acid sequence set forth in SEQ ID NO: 18 is a B5R protein having the deletion of the 4 SCR domains.

[0137] The nucleotide sequences set forth in SEQ ID NOs: 19 and 20 are the sequences of loop sequences at both ends in LC16mO VGF-SP-LucGFP/O1L-p7.5-DsRed.

[0138] The nucleotide sequence set forth in SEQ ID NO: 21 is the sequence except the loop sequences at both ends in LC16mO VGF-SP-LucGFP/O1L-p7.5-DsRed.

[0139] The nucleotide sequence set forth in SEQ ID NO: 22 is a DNA fragment containing the p7.5k promoter and the DsRed fragment.

[0140] The nucleotide sequence set forth in SEQ ID NO: 23 is a polynucleotide containing the murine IL-12 gene.

Sequence CWU 1

1

23137DNAArtificial SequencepTagBFP-N vector forward primer 1atggccggac cggccaccgg tcgccaccat gagcgag 37241DNAArtificial SequencepTagBFP-N vector reverse primer 2tcgaattcgc tagcggccgc ttaattaagc ttgtgcccca g 41318DNAArtificial SequenceB4R forward primer 3cagtcacgac gttgtaaa 18473DNAArtificial SequenceB4R reverse primer 4catgcgcacc ttgaagcgca tgaactcctt gatgacgtcc tcggaggagg ccatttttat 60ttatgagcgt taa 73520DNAArtificial SequenceDsRed forward primer 5gagttcatgc gcttcaaggt 20699DNAArtificial SequenceDsRed reverse primer 6ctcaattgat tctagctata agtctttaat cttttgatac ttgttcgtta ttaattatta 60attattttaa cggatttata tctacaggaa caggtggtg 9972379DNAArtificial Sequencepolynucleotide comprising human IL-12 7accggtcgcc accatgtgtc atcagcaact tgtcatcagc tggttttcac tcgtgtttct 60tgccagccct ttggtagcga tttgggaact caagaaagac gtgtatgtcg ttgagctgga 120ttggtatcct gatgcccctg gagagatggt ggtgctgacc tgtgatactc ccgaagagga 180tgggataacc tggacccttg accagtcctc tgaagtcctg gggagtggca aaactctgac 240gattcaggtg aaagagtttg gcgacgctgg ccagtacacc tgtcataagg gtggcgaagt 300actgtctcat tcccttctgc tgctgcacaa gaaagaggac gggatttggt caacagacat 360tctgaaagac cagaaggaac cgaagaacaa aacgttcctc cgctgtgagg cgaagaacta 420ctcaggcaga ttcacatgct ggtggctgac tacaatcagc actgatctga cgttctccgt 480caagagttct cgaggaagct ctgatccgca aggagtcaca tgcggtgcag ccactctgag 540cgctgagagg gtgagaggag acaacaaaga gtacgagtat tccgtggagt gccaggaaga 600ttccgcctgt ccagccgcag aagaaagctt gcctatcgag gtgatggttg atgctgttca 660caaactcaag tacgagaatt acacctccag cttctttatc cgggacatca tcaaacccga 720tccacccaag aatctgcagt tgaaacccct caagaactca cgtcaggttg aggtgtcttg 780ggagtatccc gatacatggt caacaccaca cagttatttc agcctgacct tttgcgtcca 840ggtgcaaggg aagagcaagc gcgaaaagaa agacagggtg ttcaccgaca agactagtgc 900taccgtgatt tgccggaaga atgccagcat atctgttaga gcacaggaca ggtactactc 960ctcctcttgg agtgaatggg catcagtacc atgcagctga tgcatctagg gcggccaatt 1020ccgcccctct ccctcccccc cccctaacgt tactggccga agccgcttgg aataaggccg 1080gtgtgcgttt gtctatatgt gattttccac catattgccg tcttttggca atgtgagggc 1140ccggaaacct ggccctgtct tcttgacgag cattcctagg ggtctttccc ctctcgccaa 1200aggaatgcaa ggtctgttga atgtcgtgaa ggaagcagtt cctctggaag cttcttgaag 1260acaaacaacg tctgtagcga ccctttgcag gcagcggaac cccccacctg gcgacaggtg 1320cctctgcggc caaaagccac gtgtataaga tacacctgca aaggcggcac aaccccagtg 1380ccacgttgtg agttggatag ttgtggaaag agtcaaatgg ctctcctcaa gcgtattcaa 1440caaggggctg aaggatgccc agaaggtacc ccattgtatg ggatctgatc tggggcctcg 1500gtgcacatgc tttacatgtg tttagtcgag gttaaaaaaa cgtctaggcc ccccgaacca 1560cggggacgtg gttttccttt gaaaaacacg atgataagct tgccaatgtg gcctcctggt 1620agtgcgtcac agccaccacc cagtcccgca gcagctactg gattgcatcc agctgctaga 1680cctgtctctc tgcaatgtag gctgagcatg tgtccagcta ggagcttgct gcttgttgcc 1740acgcttgtgc tcctggacca cctgtcattg gcacgcaatc tgcccgttgc cactcccgat 1800ccaggcatgt ttccgtgcct ccatcactct cagaacctcc tgcgggcagt cagcaatatg 1860ctgcagaaag cgaggcaaac actggagttt tacccgtgta ccagcgaaga gatagatcac 1920gaggacatta ccaaggacaa gacgtcaaca gtggaagctt gtctgcctct ggagctcaca 1980aagaatgagt cctgcctgaa tagccgtgaa accagtttca tcaccaatgg gtcttgcttg 2040gctagtcgca aaacatcctt catgatggca ttgtgccttt cctccatcta tgaggatctc 2100aagatgtatc aggtggagtt caaaaccatg aacgccaaac tgctgatgga tcccaaacga 2160cagatctttc tcgatcagaa catgcttgcc gtaatcgacg aactgatgca agccctgaac 2220ttcaacagcg aaactgtgcc tcagaagtct agccttgaag agcccgactt ctacaaaacc 2280aagatcaagc tgtgcatact cctgcatgcc tttcggatta gagccgtgac tattgacaga 2340gtcatgtcct acctgaacgc ctcatgagct agcgaattc 23798559DNAArtificial Sequencepolynucleotide comprising human IL-7 8accggtcgcc accatgtttc atgtctcttt tcggtacatc tttggacttc cacccctgat 60actggtgttg ctgcctgtag cctcatcaga ctgtgacatt gaaggcaaag acggcaaaca 120gtatgagagc gttctcatgg tgagcatcga tcagctcctt gactccatga aggaaattgg 180ctccaattgc ctcaataacg agttcaactt cttcaaacgt cacatttgcg atgccaacaa 240agaggggatg ttcctgttta gagccgctcg aaagctcagg cagttcctga agatgaactc 300tactggggat ttcgatctgc atctgctgaa agtgagtgaa gggactacga tactgctgaa 360ttgtaccgga caagtcaaag gaagaaagcc cgcagctttg ggtgaagcgc aaccgacaaa 420gagtctggag gagaataaga gcctgaaaga acagaagaag ctcaatgacc tttgctttct 480gaaacgcctt ttgcaggaga tcaagacctg ttggaacaag atcctgatgg gtacaaagga 540gcactgagct agcgaattc 55993082DNAArtificial SequenceCodon optimized LacZ 9accggtcgcc accatggacc cggtggtgct gcagaggcgg gattgggaga atcctggggt 60gacgcagctg aatcggctgg ctgctcaccc accatttgca tcatggagaa attccgaaga 120ggcccggacc gaccgcccct ctcagcagct cagaagtctt aatggagaat ggcgcttcgc 180atggtttcct gctcccgagg ctgtaccgga aagttggctc gagtgcgatt tgcccgaggc 240agataccgtc gtggttccct ccaactggca gatgcacggc tatgatgccc ctatctacac 300caatgtcact taccctataa cagtgaaccc accctttgtg cctaccgaga atcccaccgg 360atgctacagt ctgacattta acgtggacga gtcttggctg caggaaggcc agactagaat 420catcttcgat ggtgtcaaca gcgcttttca tctgtggtgc aacgggcgtt gggtgggtta 480cggccaagac agtaggctcc cttctgaatt cgatctctct gccttcctgc gggccggtga 540gaatagactt gccgttatgg ttctgcgttg gagcgacggt tcctacctgg aggaccagga 600tatgtggagg atgtctggca ttttccgaga tgtgagcctc cttcacaaac ctaccactca 660aatctccgac tttcatgttg ccacaaggtt caacgacgac ttttcacgcg ctgttctgga 720ggccgaggtc caaatgtgcg gcgaactgcg cgattatctg cgcgtgactg tgagcctttg 780gcaaggagag acacaggtgg catcaggcac cgcacccttc ggcggagaaa tcatcgacga 840acggggagga tatgctgata gggttactct taggctgaat gtagaaaacc ccaagctctg 900gtctgcagaa atacctaacc tctatcgcgc agttgtggaa ctgcacacgg cagacgggac 960cctgattgaa gccgaagcct gtgacgtcgg cttccgtgaa gtgcgcatcg agaatgggct 1020gctccttctt aacggtaagc cactgttgat cagaggcgtg aataggcatg agcatcatcc 1080gctccacgga caggtgatgg atgagcagac aatggttcag gacatactct tgatgaaaca 1140gaacaacttc aatgccgtgc gctgtagcca ctaccctaat cacccactgt ggtataccct 1200gtgtgacagg tacggcctgt atgtcgtgga tgaggcaaac attgaaactc atggcatggt 1260gccaatgaat cggctgacag atgaccccag atggctgccc gccatgtcag agcgtgtgac 1320caggatggta cagcgggaca gaaatcaccc cagtgtcata atctggtccc ttgggaacga 1380atcagggcat ggtgcaaacc acgatgctct gtaccgctgg attaagagcg ttgaccctag 1440tcggccagtg cagtatgaag gtggaggcgc cgataccact gcaactgaca ttatttgccc 1500aatgtacgct cgggtcgacg aggatcaacc gttccctgcg gtcccaaagt ggagcattaa 1560gaaatggctg tctttgcctg gagaaacacg cccgctgatt ctgtgcgaat atgcccacgc 1620aatggggaac tccctgggcg ggtttgcaaa gtattggcag gcttttcgcc agtatccacg 1680actgcaggga ggctttgtgt gggactgggt agatcagagc ctgatcaaat acgacgaaaa 1740tggcaatcca tggtccgcct atggaggtga ctttggtgat acccctaatg acaggcagtt 1800ttgcatgaac ggactcgtct ttgcagatcg aactccacat ccggccctga ctgaggccaa 1860gcatcagcag caattcttcc agtttcggct gtctgggcag accattgagg tgacttccga 1920gtacttgttt cgacacagcg acaatgagct gctgcactgg atggtggccc tcgatggcaa 1980accactggcc tcaggagagg tgcccctgga tgtagcgccc caggggaaac agcttatcga 2040gttgcccgaa ctgccccaac ccgagtctgc tgggcaactc tggcttaccg tgcgagtcgt 2100tcagccaaat gccactgcct ggtccgaggc tggccacatt agcgcatggc agcagtggag 2160actggctgag aacctcagcg ttacccttcc cgcagcctct cacgccatcc ctcacttgac 2220cactagtgag atggacttct gtatcgagct gggcaacaaa cgctggcagt ttaacagaca 2280gtcaggcttc ttgtcccaga tgtggattgg cgacaagaag cagctgttga cccctttgcg 2340ggatcagttc acaagggcgc ctctggacaa tgacatcgga gtgagcgagg ctacacgaat 2400agatccaaac gcgtgggtcg agaggtggaa ggcggctggg cactaccaag ctgaagcggc 2460cctgttgcaa tgtaccgccg atacgctcgc cgatgccgtc ctcattacga cagcccacgc 2520ttggcagcac cagggcaaaa cactgtttat ctcccgtaag acatacagaa tcgatggcag 2580cggtcaaatg gccattacgg tagacgtgga agttgcgtca gatacacccc atcccgcgag 2640gatcggactg aactgtcaat tggcccaagt cgcagagaga gtgaactggc tgggactcgg 2700gcctcaggag aattatccag accggctcac agccgcttgc ttcgataggt gggaccttcc 2760actctctgat atgtacaccc catacgtgtt cccctcagag aatggcctgc ggtgtgggac 2820acgagaactg aactacggac cgcatcagtg gagaggggac ttccagttca acatcagccg 2880gtatagtcag cagcagctga tggaaacgtc ccatagacat ctgctgcacg ctgaggaagg 2940gacatggctg aacattgacg ggttccacat gggaataggt ggcgatgaca gctggtcccc 3000tagcgtaagc gccgagtttc aactgagtgc tgggagatat cattaccaac tggtctggtg 3060ccagaaatga gctagcgaat tc 30821020DNAArtificial SequenceVGF forward primer 10ggtaacgcta tcgaaacgac 201120DNAArtificial SequenceVGF reverse primer 11ttagttcgtc gagtgaacct 201220DNAArtificial SequenceO1L forward primer 12acagggatta agacggaaag 201320DNAArtificial SequenceO1L reverse primer 13gtcaacaagc atcttccaac 201420DNAArtificial SequenceB5R forward primer-for PCR 14cgtataatac gttggtctat 201520DNAArtificial SequenceB5R reverse primer-for PCR 15gatcgtgcca atagtagtta 201613DNAArtificial Sequence5' restriction enzyme site in SEQ ID NOS 7 to 9 16accggtcgcc acc 131712DNAArtificial Sequence3' restriction enzyme site in SEQ ID NOS 7 to 9 17gctagcgaat tc 1218101PRTArtificial Sequence4 SCR domains deleted B5R protein 18Met Lys Thr Ile Ser Val Val Thr Leu Leu Cys Val Leu Pro Ala Val1 5 10 15Val Tyr Ser Thr Cys Val Arg Ser Asn Glu Lys Phe Asp Pro Val Asp 20 25 30Asp Gly Pro Asp Asp Glu Thr Asp Leu Ser Lys Leu Ser Lys Asp Val 35 40 45Val Gln Tyr Glu Gln Glu Ile Glu Ser Leu Glu Ala Thr Tyr His Ile 50 55 60Ile Ile Val Ala Leu Thr Ile Met Gly Val Ile Phe Leu Ile Ser Val65 70 75 80Ile Val Leu Val Cys Ser Cys Asp Lys Asn Asn Asp Gln Tyr Lys Phe 85 90 95His Lys Leu Leu Pro 10019104DNAArtificial SequencePartial genome sequence of Vaccinia virus 19tagtaaaatt aaattaatta taaaattata tatataattt actaacttta gttagataaa 60ttaataatat ataagtttta gtacattaat attatatttt aaat 10420104DNAArtificial SequencePartial genome sequence of Vaccinia virus 20atttaaaata taatattaat gtactaaaac ttatatatta ttaatttatc taactaaagt 60tagtaaatta tatatataat tttataatta atttaatttt acta 10421202489DNAArtificial SequencePartial genome sequence of modified vaccinia virus 21attttattta gtgtctagaa aaaaatgtgt gacccatgac tgtaggaaac tctagagtgt 60aagaaagatc gatcgcttta tagagaccat cagaaagagg tttaatattt ttgtgagacc 120atcgaagaga gaaagagata aaactttttt acgactccat cagaaagagg tttaatattt 180ttgtgagacc atcgaagaga gaaagagata aaactttttt acgactccat cagaaagagg 240tttaatattt ttgtgagacc atcgaaggag aaagagataa aactttttta cgactccatc 300agaaagaggt ttaatatttt tgtgagacca tcgaagagag aaagagataa aactttttta 360cgactccatc agaaagaggt ttaatatttt tgtgagacca tcgaagagag aaagagataa 420aactttttta cgactccatc agaaagaggt ttaatatttt tgtgagacca tcgaagagag 480aaagagataa aactttttta cgactccatc agaaagaggt ttaatatttt tgtgagacca 540tcgaagagag aaagagataa aactttttta cgactccatc agaaagaggt ttaatatttt 600tgtgagacca tcgaagagag aaagagataa aactttttta cgactccatc agaaagaggt 660ttaatatttt tgtgagacca tcgaagagag aaagagataa aactttttta cgactccatc 720agaaagaggt ttaatatttt tgtgagacca tcgaagagag aaagagataa aactttttta 780cgactccatc agaaagaggt ttaatatttt tgtgagacca tcgaagagag aaagagataa 840aactttttta cgactccatc agaaagaggt ttaatatttt tgtgagacca tcgaagagag 900aaagagataa aactttttta cgactccatc agaaagaggt ttaatatttt tgtgagacca 960tcgaagagag aaagagataa aactttttta cgactccatc agaaagaggt ttaatatttt 1020tgtgagacca tcgaagagag aaagagataa aactttttta cgactccatc agaaagaggt 1080ttaatatttt tgtgagacca tcgaagagag aaagagataa aactttttta cgactccatc 1140agaaagaggt ttaatatttt tgtgagacca tcgaagagag aaagagataa aactttttta 1200cgactccatc agaaagaggt ttaatatttt tgtgagacca tcgaagagag aaagagataa 1260aactttttta cgactccatc agaaagaggt ttaatatttt tgtgagacca tcgaagagag 1320aaagagataa aactttttta cgactccatc agaaagaggt ttaatatttt tgtgagacca 1380tcgaagagag aaagagataa aactttttta cgactccatc agaaagaggt ttaatatttt 1440tgtgagacca tcgaagagag aaagagataa aactttttta cgactccatc agaaagaggt 1500ttaatatttt tgtgagacca tcgaagagag aaagagaaag agatagttag tctagatatt 1560tttcttagta caaaagtcaa tgttttaaaa tatatggaca agaatttgtc tgtataaaaa 1620cttgtgtgaa attttgtacc aaagaaaaaa tgtgagcagt atcccctaca tggattttac 1680tagatcattt atataccaaa aaatattata cgatctacgt tttattatat gattttaacg 1740tgtaaattat aaacattatt ttatgatata caattgtctg gtaacctaga tgggcatagg 1800ggatgttgat aagctcgacg agtatatgtt gttggacgtt attgtttaag aaatagttga 1860tgcatcagaa agagaataaa aaatatttta gtgagaccat cgaagagaga aagagataaa 1920acttttttac gactccatca gaaagaggtt taatattttt gtgagaccat cgaagagaga 1980aagagaataa aaatatttta tgactccatt gaagagagaa agagaaaatg agaatgagaa 2040taaaaatatt ttagtgacac catcagaaag aggtttaata tttttgtgag accatcgaag 2100agagaaagag aataaaaata ttttatgact ccattgaaga gagaaagaga aaatgagaat 2160gagaataaaa atattttagt gacaccatca gaaagaggtt taatattttt tatgagacca 2220tcaaagagag aaagaaaata aaaatatttt tgtaaaactt tttttatgag accatcaaag 2280agagaaagag aataaaaata tttttgtaaa acttttttta tgagaccatc aaagagagaa 2340agagaataaa aatatttttg taaaactttt tttatgagac catcaaagag agaaagagaa 2400taaaaatatt tttgtaaaac tttttttatg agaccatcaa agagagaaag agaataaaaa 2460tatttttgta aaactttttt tatgagacca tcaaagagag aaagagaata aaaatatttt 2520tgtaaaactt tttttatgag accatcaaag agagaaagag aataaaaata tttttgtaaa 2580acttttttta tgagaccatc aaagagagaa agagaataaa aatatttttg taaaactttt 2640tttatgagac catcaaagag agaaagagaa taaaaatatt tttgtaaaac tttttttatg 2700agaccatcaa agagagaaag agaataaaaa tatttttgta aaactttttt tatgagacca 2760tcaaagagag aaagagaata aaaatatttt tgtaaaactt tttttatgag accatcaaag 2820agagaaagag aataaaaata tttttgtaaa acttttttta tgagaccatc aaagagagaa 2880agagaataaa aatatttttg taaaactttt tttatgagac catcaaagag agaaagagaa 2940taaaaatatt tttgtaaaac tttttttatg agaccatcaa agagagaaag agaataaaaa 3000tatttttgta aaactttttt tatgagacca tcaaagagag aaagagaata aaaatatttt 3060tgtaaaactt tttttatgag accatcaaag agagaaagag aataaaaata tttttgtaaa 3120acttttttta tgagaccatc aaagagagaa agagaataaa aatatttttg taaaactttt 3180tttatgagac catcaaagag agaaagagaa taaaaatatt tttgtaaaac tttttttatg 3240agaccatcaa agagagaaag agaataaaaa tatttttgta aaactttttt tatgagacca 3300tcaaagagag aaagagaata aaaatatttt tgtaaaactt tttttatgag accatcaaag 3360agagaaagag aataaaaata tttttgtaaa acttttttta tgataccatc aaagagagaa 3420agagaataaa aatatttttg taaaactttt tttatgagac catcaaagag agaaagagaa 3480taaaaatatt tttgtaaaac tttttttatg agaccatcaa agagagaaag agaataaaaa 3540tatttttgta aaactttttt tatgagacca tcaaagagag aaagagaata aaaatatttt 3600tgtaaaactt tttttatgag accatcaaag agagaaagag aataaaaata tttttgtaaa 3660acttttttta tgagaccatc aaagagagaa agagaataaa aatatttttg taaaactttt 3720tttatgagac catcaaagag agaaagagaa taaaaatatt tttgtaaaac tttttttatg 3780agaccatcaa agagagaaag agaataaaaa tatttttgta aaactttttt tatgagacca 3840tcaaagagag aaagagaata aaaatatttt tgtaaaactt tttttatgag accatcaaag 3900agagaaagag aataaaaata tttttgtaaa acttttttta tgagaccatc aaagagagaa 3960agagaataaa aatatttttg taaaactttt tttatgagac catcaaagag agaaagagaa 4020taaaaatatt tttgtaaaac tttttttatg agaccatcaa agagagaaag agaataaaaa 4080tatttttgta aaactttttt tatgagacca tcaaagagag aaagagaata aaaatatttt 4140tgtaaaactt tttttatgag accatcaaag agagaaagag aataaaaata tttttgtaaa 4200acttttttta tgagaccatc aaagagagaa agagaataaa aatatttttg taaaactttt 4260tttatgagac catcaaagag agaaagagaa taaaaatatt tttgtaaaac tttttttatg 4320agaccatcaa agagagaaag agaataaaaa tatttttgta aaactttttt tatgagacca 4380tcaaagagag aaagagaata aaaatatttt tgtaaaactt tttttatgag accatcaaag 4440agagaaagag aataaaaata tttttgtaaa acttttttta tgagaccatc aaagagagaa 4500agagaataaa aatatttttg taaaactttt tttatgagac catcaaagag agaaagagaa 4560taaaaatatt tttgtaaaac tttttttatg agaccatcaa agagagaaag agaataaaaa 4620tatttttgta aaactttttt tatgagacca tcaaagagag aaagagaata aaaatatttt 4680tgtaaaactt tttttatgag accatcaaag agagaaagag aataaaaata tttttgtaaa 4740acttttttta tgagaccatc agaaagaggt ttaatatttt tgtgataccc tgaaaggaaa 4800taggaatagg aataggaata ggaatagtgt cataatcgta tcacactatt gagacagaaa 4860aagaagaagt cgcgagaggt aactttttgt gaatgtagtt aagaacattt ttgttttgca 4920aaccggaata tagtgtccgg tacacttttt taattcgtgg tgtgcctgaa tcgttcgatt 4980aaccctactc atccaatttc agatgaatag agttatcgat tcagacacac gctttgagtt 5040ttgttgaatc gatgagtgaa gtatcatcgg ttgcaccttc agatgccgat ccgtcgacat 5100acttgaatcc atccttgacc tcaagttcag atgattcctt gcacatgtct ccgatacgaa 5160cgctaaactc tagattcttg acacattttg tatcgacgat cgttgaaccg atgatatctt 5220cgtaactcac tttcttatga gagatgttag acccgagtac tggatgggtc ttgatgtcgc 5280tgtctttctc ttcttcgcta catctgatgt cgatagacac ctcacagtct ttgatcatag 5340caagagcttc ttcatgagtg atcgcgggag agtccttacc ttgtcctggg gacacgctgg 5400acaatctagc attcactgtg tttccatcag cggattctga gatggattta atctgaggac 5460atttggtgaa tccaaagttc attctcagac ctccaccgat gatggagtaa taagtggtag 5520gaggatctac atcctcgact gatgtggaat catcttctga ttccacctcg ggatctggat 5580ctgactcgga ctctgtaatt tccgttacgg attggcaaat cttatcattg gtcggtgttt 5640ggtcttgctt tgtgactttg ataataacat cgattcccat atgatgtttg ttttcttctt 5700ccgtacacga ggaggaggat gaggatgatt gctgaagact ggcaggcata gcagctgccg 5760ccaggcacat gcatgccagt acgatatatt gtttcataat tgctattgat tgagtactgt 5820tctttatgat tctacttcct taccgtgcaa taaattagaa tatattttct acttttacga 5880gaaattaatt attgtattta ttatttatgg gtgaaaaact tactataaaa agtgggtggg 5940tttggaatta gtgatcagtt tatgtatatc gcaactaccg ggcatatggc tatcgacatc 6000gagaacatta cccacatgat aagagattgt atcagtttcg

tagtcttgag tattggtatt 6060actatatagt atatagatgt cgcccactag agttactgtc tccgaatgcg gcatgatagt 6120atcattcttt gctttcgtta actgtttgga ggaagaatct ttgttattgc atttaatctc 6180gaaattcaga gtgcacacct ttctcctgta aagaaacctg aagtcgctac cttattaagg 6240acggagaagt atccatcacg aaagacggga tcgcagtctt tatgattcat agtaatagtt 6300agttccgacg ttgagatgga ttcgctgaga ccggtagtgg tcgtccgagt acacgacgtg 6360tcgttaactg gatacagatt aatttccaca tcgatatagt taaaggtatt actgggtacg 6420ggttcgcatt tatctgcgga agagacggtg tgagaatatg ttccgagacc acacggagaa 6480cagatgacgt ctccggatac tccgtatcct attccacatt ttgtttggga aacacatgcc 6540ttgcatccgg atgatccttt gagaagacaa taatatccgg gagagcattc acagattcta 6600ttgtgagtcg tgttacacga tcgcgtcttc cgttacaact tagacaagcg ggtaaatgat 6660tattgcgaga tgtgaaggta cccgaaccac acggcgtaca ttgtgtgtta gtcttgctat 6720cgcataatct ggaagcgtat gttcccggac acaaattatg gcgtttgtat tcgttgtctt 6780tacactttcc atcggatggt gcatgcggtg ctatatctct tccgtttatt attatacatg 6840agagaaacaa tatatacgag tataatacgg acttcatgat ttaataatgt agtaatcgtc 6900gtcttgttcc tgtttcctac ttctccaatc atatagatat tttctttcta tcatggataa 6960tatttgtaat ggttctttcc gtacaacata ctgtttagat gatattgcgc ataatttccg 7020gaggcaaata cgatagtcta gattgaccga tggtagactc taatttattg agtgctttgt 7080cgacgagttt acttttacgc tccatcgata gatggcactg ttctatgaga tcgtcgtaca 7140tgggaaatga aatgtgactg tctgaatgta tggctttaag atagctgtga taccgtatac 7200aggtcggtgt cggagattcg aatctcttta aggcgactta tgtcacgatg atggaatcta 7260tcttatcgaa tgatatattt ttcataaata cacttttata gtcctcgttt aaacagaatt 7320tactatgtag ttccgcgaat gactcgtccc ttaataggca gtaggctagt atctttttta 7380cgtagtaatc gtcgtaggga gagacatctt gtagaacaac gatttaatca taggtagaga 7440tactttcagt ctgtggtgga tgatgtcatt cacaacatcc gccttgtata tgatgtttct 7500gttttcaaac accaagtcga ataccgtctt tagtcggaag gttgatgtcg tatccgatgt 7560atgaggcaac attgttgtta caattttgaa aggcggtatt atagtattcg tctttctgaa 7620tgtcgaacct atctaataga taccgtagta tattgagagt gtatccttga ttatgtttta 7680tgaatagata aagtagatgt tgtccttctt ccttttgttc gtgccaattg agtaacatta 7740tgagaatatg acctgttgca caatcgttcc atgatgggtg tacaatcaag attattacgt 7800atcctcgaga taaaagagca tacaccacac gaggactatg tttggtatac tgttgaaggt 7860aagtgtgtaa ccgcgttaat gtttgctcca taatctatta tcgcgtagat gaatcgcttc 7920tcggctcgca tcttagtgtg acttgacttg taataattgc tttcgtagaa cgtggatatg 7980tgtttacagt agtaatgaag agaagtgagt tcatcctcgt cggcgcaatt agggtcggat 8040cctttgtaca gaacgtaata gtttaagctc ccattgaatt tatatctaag ataacacagc 8100aatagatcgg atgatttact aaagtcatca atggtgtccg ttagtatatc aaagatcttg 8160ttatcgattg atagtggtca tccttgctat caaagttacg catgccgtgg tgtaacaata 8220tctttaatac agatggatta aatcgtgtat tcatcgtata gcaatgtaat ggagagttac 8280ctcgtttatt cagatcgcag tgtttaataa ctagcttaaa cagatgagac gatgtattca 8340catcaaagaa cgtgaaatac atatgacaga cattgttgac agaaacgtga ccttcattct 8400taccgtcgtc cataaatacg ttaggtatgt accacatact gtcgcgaacg atgcgtacaa 8460tctcgtccat ctcataatga tttacttttt cataattaaa gatgtgaaag aaaaacagaa 8520caatatattt ttttagtaat gtttatgcga gacatataaa ataaactccg tgtttatgat 8580gccggtaaat gtttttatca tcttggacgg aatcgatttt gtaatatgtc atggaaacaa 8640atgaaacagg acattatcgc tccatgataa attatttaat ggagtaataa agtatctcca 8700tgggtaattt cgaaatcaag ttatcgtctg tattaatgtt gtccactatg gagtcgatcc 8760tctcattgtt ctttacagtt tctgtaatga tggacgttag ttcttttttg taccatttga 8820tgtcggattc tttgcgtatc tcagtctgtg gcgtttgctt tgtttaaata atatatcaaa 8880catggagacg cctgatatgt aggcattctt cattctatta atgtctgctc tatagcgctt 8940tagttcctta tgacgaccgg cgatatcata ctttacttta gaaggaaaat catcatctat 9000gattaaggcg tatctgatac aggcgaataa tggttcagga tatagatagc gtatatctct 9060attaaatgcg tcaatcatag tctctagagt gggatggtag ctaagtaata aatcaactat 9120cctcgttttg ttttctcttt ggtaactgct tttctggatg gccgtattga ttatcgagcg 9180tgatgttgta acactcgctc catattccaa taaccgcttt gcaaattgta tattattgac 9240atcgaccgcg taatatagta gagttatcga tcatatctat atcatccatg tacttgctta 9300gtatatcaaa tacatctatt agtatggttt cataacagtg atacccgcaa ttattaaatc 9360tcgataatat cagaccgtac atacatagac ggccattgtt cgatacgtga tttacagccg 9420cgtgtccata ttttccacga taaaccttac gacgtttaca tcgacgagat tattattaac 9480aaagtagtcg tgtagaggat agttgttgtc cgtcgtctta tccatggttg ctccgttatc 9540caacatgcat tgaatgatag gtatacttac catatcgccg taatgtaagt agtttatcaa 9600catggcttgt acatcctgtt gtctaaatct ctttagaatg ttatcgatga tgtagtggtt 9660atattctctg gaatcgtacg aagtaatact acgcattacg tcgacaagag tatgacgtct 9720ctcaataaga agattaacga tttccatgtc tacattatat ggggttactc taaatcgctt 9780gtttagataa tacgcctcta atatagggct gacgtcgtat actctacacg tgtccacatc 9840ctttattaat aataatttaa caatctctat atctatggtt gagcaagacc agtagtattg 9900gatgggtaaa gatcctcctt cgtctctgcc atggatggaa acattgttat cgatcaaaca 9960tttaattaca tccttggata gagattgaga ttctctatga gacgatatat agtaatgaag 10020agagttctta cacatatcac tgtcgtacat acaggtacga aatacgtaac cggtgctgta 10080acattctgat ttaagaagcc atagcaatac ttctggtctc ggattaggcg tcgttacgta 10140tatatccacc aatccgagac cattgattgc ataattcgta ttcttggacg gacgtatccg 10200tttatccaca attaggtatt ttagcagacg taagtcgata ttatccgaat acagatcgaa 10260atcatttata ttcgacttga gttcgttaga ggaatttgaa tagctggata tcagtagatg 10320cacaatctga gattttacgt atctatgctt actgtatact cctagcggag ttaatccttc 10380gttgtttcta caaagtctct cgactccgcg agagagtaac agccgaacaa tcttaatgtc 10440tgtatcgcat ttattggaga cgtaacaatg tagcgcattg tttcctcgtc tatctatatg 10500ttttgataag ttgtgacacg tttcaatttc tagttttatt tttttgtacg tcacatcttc 10560atccagtaga cgacatagaa tagtgcactc tctaccacaa taatccatag ctattctggt 10620gctaattatt cctatttcac gaaaaatgat aaaggcaatc attcctcata agatgataaa 10680aagtgtagtg agagagcatg aaggagattt agtatttagc agtgcggata tgatccaaga 10740gggtgagata gtcgttctcg ttcagaatct ttcgcagcat aagtagtatg tcgatatact 10800tatcgttgaa gactcttcca gagacgatag ctgattgagt acaaagtcca atgattgcac 10860gaagttcttc ggcggttttc atggagtcat ttctgatgaa acatttaatg atctccacgc 10920aattgtccca cggaagtgaa tccttcaact caccaccaaa gagctccgtt gcatcagttc 10980tgaaagagat gagaagcctg tagagagacc ctgcgctttc tctatgggtc catctatgag 11040aaacccacag gatgtattca gtcagacaat gtctgacgtc ggccacggta ttcagggagt 11100ccttagtagc gtggcaatga cagggtctga actgggcaca aggaaaggcc attgtgaagg 11160tagacgaagg ttaacctgat ggtagacctg tagccgtcta tgctaataga gggctttaat 11220ttccattttt taatggggtt gtggatgagg aatgagagtg atatcatatt gagatacgta 11280gttatgtaga ggtgtatttc ctatattatt tactttcggt ttcatatttt accaactctt 11340taataaattt cttttcacga tgcatcttat taaatgacgt tttctcataa gtggacatat 11400agatgcagaa gtaatgaaga aaagtattac ctctatcatc tacataatta gggtctgctc 11460ctttttttaa caacttatac agtacgtagt agtagtttat cggttttaaa tcaagtctag 11520aatatatagt ggattaatat atttttatat tcgctaaagc tatctatact atcagaaagc 11580atatcattct caacttcatc atgagttaaa tatttgtgta atggaatgtg accatcactg 11640tcatgacata ctcctttaat aggtttttta aaacagatga ttcaaatcct tcattcatta 11700gataacagtg taacggagtc gtaccttcta ctagtttgtt tatatcacag cattctacaa 11760acagtctaaa caatagagaa gacggacaga ctttaacgta taaatgacac atgttatcga 11820tattcgttga tgaattatta ttaaacgtag ttatgataaa tgattctaac gacatttctc 11880gctagagata aaatctagta tcgtatcata ctcgcatagc atagtttttc ataattaata 11940caatatttaa aagacttatt cggaaagtat tttaatacat gtatcatcga tggagatcca 12000tatgaggagt cacttgtagt tcttcagtag taataacagt gctatcatcg atagtataat 12060tatatgttgt tgtaattgga gtaactgttg gtagttcttc cgtggaatca ataattatac 12120taacagcaat agtataatta tataaatatg ttccgttgat atcacatatt ttaatgaact 12180catttctaac accctcagct atatctgtcc aattaaatgt agccaacaat ctactacgtt 12240ctctttgatt gactacttgt acggtagcga cgctacacta tctttattgt cttctacatg 12300ctccaattga atgtcatgat acaacgcagt ttttcttatg catgtttcat aacaccacga 12360acatgtcgca gtaagataat ttttgtaaat tcatgattgc cggtcataaa caagcccgtc 12420aataattgtg gctatatatt cagtttatag agcaaaataa ttaagcacaa tagcgcttaa 12480tctcaaaata tgttatgttt atttttttca tattaaacat actggttaaa atcctctaaa 12540ggctgatctt catctataaa tcaagatcat aattacattt agacagtggt ttcatgttta 12600taaaaatgtt ctttttgtgt gaataaggaa tatactaatc aataatcaac catcgacccc 12660attacgatag tatgcaggca accccccatt agagaggtac gtgtaatcag tctctccagt 12720tttagtattt ttataagtca ttgttacata aacggctttt aaacagtctc ctcgataata 12780agccatatct ggaaatttat taaatactcg agtcatttta cgcacggtca aaaaagtaag 12840taatgtcgac gacttcttac attctataga aacacctaga atactcattt tcttttggaa 12900aatatcctca gactctgatt tgaacaatgc acgacctata gtaaaccgtg accaataagt 12960tatattagtc aatggtatat ccaaaccatc aagtgtggat agtacgccga tagtccagtc 13020tttggtatcg atagtgtagt tattgaactg agaagttacc gtatagtctt tttggtcatc 13080tctaaacaag gaaactaata cctctacact attgaacgat ttatcttccg taatgggtgg 13140aataacggga atataaagtg gactagcgat ggatgaagtc acgaatataa gacacgctat 13200taatccgtat atcatcattt tgatattact tataataacg atttgtttaa tttttagttt 13260atactattaa ttgtaaatga tattattatt ttttttaagt attatcagct ttagtttata 13320ctattactat ttgtaatatt tagacataga taaacgtgat aaaagtctat ttgtttatat 13380ttattgcgga tagcagtatt tccctataaa aagtatacgt cctgtgttgt ctttaatcat 13440gtacatgaat ggatggttta tgtagacctt cgtacgatat accatcgaaa agttagtcat 13500aaatactcct gtaacggccg atgcttctgt atactcctca ttaacatcta taaacgtcgt 13560atgtagaaat ttttctacag tgatagtttc attacacatc ttgctaaaat ctgcataata 13620tccgaatata ttagtaagtc ctaaattttc taaaatcggt accagattat acggttctgt 13680catttccact ttaaactttg gcatatacaa gtctatactt ttagtagata acataccaca 13740ccatttttta aatttttcat ctgttatatt tttttctatg ttatatatac cttctatgtc 13800gtccggtagt ataattacca tactagagtt tccctcgtat ggaatatcga taatagagaa 13860tcctccgaat aattcattaa tatgtacata ttgcaagtta ttctcggtac ccaccatcat 13920atcaacgctg gtaactatat tcttagaaat ataaaacttg tctgtatatg taagatgttt 13980agaaaatgga tatttccaca ttgctttaaa atggacggcg ctaacaactg tcatacgagt 14040attaatggat agcggactag tcaataagga attaatttta ccatttgtca ttgtcttaac 14100ccattcgttg attagttcct ttgtttggtt agcattatta aagtttacag tttgaaaatc 14160gtcttttatt ttttgtagga aggaggcatg gaactcgata ctatcgctac cgtatatttt 14220atttgcggta gctagtgtcg cacaatacgg aatatctacg tccatgtcat tattgtcatc 14280gggtgtattc tcattcatat tctctatata ttttgatagt tgttcagctg tagaaccagc 14340tgctccatga tttagaatag ataaagtaga taaaatagaa actggagaaa tcaaaacatt 14400ttcatccgtg tgttttaaga ttagttcttt aaagatatcc atggtataga ccaaacaata 14460acgataacga tatatatcat aaataaataa tgttaaattt tagtttatgt ttgtaccccg 14520tattcatact taacaaattg gtattgcgta cacaatcaat catattacat accattaata 14580atgcaagcat aaaaaatcgt tagtagatgt ttctaaatat aggttccgta agcaaagaat 14640ataagaatga agcggtaatg ataaaatcaa ttgttatcta aaatgatcat actcatttat 14700tttattctat tatattaaca catacatttt taacagcaac acattcaata ttgtattgtt 14760atttttatat tatttacaca attaacaata tattattagt ttatattact gaattaataa 14820tataaaattc ccaatcttgt cataaacaca cactgagaaa cagcataaac acaaaatcca 14880tcaaaaatgt tgataaatta tctgatgttg ttgttcgctg ctatgataat cagatcattc 14940gccgatagtg gtaacgctat cgaaacgaca ttgccagaaa ttacaaacgc tacaacagat 15000attccagcta tcagattatg cggtccagag ggagatggat attgtttaca cggtgactgt 15060atccacgcta gagatattga cggtatgtat tgtagatgct ctcatggtta tacaggcatt 15120agatgtcagc atgtagtatt agtagaattc ttacttgtac agctcgtcca tgccgagagt 15180gatcccggcg gcggtcacga actccagcag gaccatgtga tcgcgcttct cgttggggtc 15240tttgctcagg gcggactggg tgctcaggta gtggttgtcg ggcagcagca cggggccgtc 15300gccgatgggg gtgttctgct ggtagtggtc ggcgagctgc acgctgccgt cctcgatgtt 15360gtggcggatc ttgaagttca ccttgatgcc gttcttctgc ttgtcggcca tgatatagac 15420gttgtggctg ttgtagttgt actccagctt gtgccccagg atgttgccgt cctccttgaa 15480gtcgatgccc ttcagctcga tgcggttcac cagggtgtcg ccctcgaact tcacctcggc 15540gcgggtcttg tagttgccgt cgtccttgaa gaagatggtg cgctcctgga cgtagccttc 15600gggcatggcg gacttgaaga agtcgtgctg cttcatgtgg tcggggtagc ggctgaagca 15660ctgcacgccg taggtcaggg tggtcacgag ggtgggccag ggcacgggca gcttgccggt 15720ggtgcagatg aacttcaggg tcagcttgcc gtaggtggca tcgccctcgc cctcgccgga 15780cacgctgaac ttgtggccgt ttacgtcgcc gtccagctcg accaggatgg gcaccacccc 15840ggtgaacagc tcctcgccct tgctcaccat ggtggctgcg gccgccacgg cgatcttgcc 15900gcccttcttg gccttaatga gaatctcgcg gatcttgcgg gcgtccaact tgccggtcag 15960tcctttaggc acctcgtcca cgaacacaac accaccgcgc agcttcttgg cggttgtaac 16020ctggctggcc acatagtcca cgatctcctt ctcggtcatg gttttaccgt gttccagcac 16080gacgactgcg gcgggcagct cgccggcatc gtcgtcgggc aggccggcga ccccggcgtc 16140gaagatgttg gggtgttgca gcaggatgct ctccagttcg gctggggcta cctggtagcc 16200cttgtatttg atcaggctct tcagccggtc cacgatgaag aagtgctcgt cctcgtccca 16260gtaggcgatg tcgccgctgt gcagccagcc gtccttgtcg atgagagcgt ttgtagcctc 16320ggggttgtta acgtagccgc tcatgatcat ggggccacgg acgcacagct cgccgcgctg 16380gttcacaccc agtgtcttac cggtgtccaa gtccaccacc ttagcctcga agaagggcac 16440caccttgcct actgcgccag gcttgtcgtc cccttcgggg gtgatcagaa tggcgctggt 16500tgtttctgtc aggccgtagc cctggcggat gcctggtagg tggaagcgtt tggccacggc 16560ctcacctacc tccttgctga gcggcgcccc gccgctggcg atctcgtgca agttgcttag 16620gtcgtacttg tcgatgagag tgctcttagc gaagaagcta aatagtgtgg gcaccagcag 16680ggcagattga atcttatagt cttgcaagct gcgcaagaat agctcctcct cgaagcggta 16740catgagcacg acccgaaagc cgcagatcaa gtagcccagc gtggtgaaca tgccgaagcc 16800gtggtgaaat ggcaccacgc tgaggatagc ggtgtcgggg atgatctggt tgccgaagat 16860ggggtcgcgg gcatgactga atcggacaca agcggtgcgg tgcggtaggg ctacgccctt 16920gggcaatccg gtactgccac tactgttcat gatcagggcg atggttttgt cccggtcgaa 16980gctctcgggc acgaagtcgt actcgttgaa gccgggtggc aaatgggaag tcacgaaggt 17040gtacatgctt tggaagccct ggtagtcggt cttgctatcc atgatgatga tcttttgtat 17100gatcggtagc ttcttttgca cgttgaggat cttttgcagc cctttcttgc tcacgaatac 17160gacggtgggc tggctgatgc ccatgctgtt cagcagctcg cgctcgttgt agatgtcgtt 17220agctggggcc acagccacac cgatgaacag ggcacccaac acgggcatga agaactgcaa 17280gctattctcg ctgcacacca cgatccgatg gtttgtattc agcccatagc gcttcatagc 17340ttctgccagc cgaacgctca tctcgaagta ctcggcgtag gtaatgtcca cctcgatatg 17400tgcgtcggta aaggcgatgg tgccgggcac cagggcgtag cgcttcatgg ctttgtgcag 17460ctgctcgccg gcggtcccgt cttcgagtgg gtagaatggc gctgggccct tcttaatgtt 17520tttggcatct tccatggccc cggccgtgca ataaattaga atagtttttc aatttttggt 17580acctcgacct tatttatatg ccaaaaaaaa aaaaaaaaaa gctgatccaa tttcgacgag 17640actatcaacg ttcagaaaac ccaaacacta caacgtcata tatcccatct cccggtatta 17700tgcttgtatt agtaggcatt attattatta cgtgttgtct attatctgtt tataggttca 17760ctcgacgaac taaactactt atacaagata tggttgtgcc ataattttta taaatttttt 17820ttatgagtat ttttacaaaa atgtataaag tgtatgtctt atgtatattt ataaaaatgc 17880taaatatgcg atgtatctat gttatttgta tttatctaaa caatacctct acctctagat 17940attatacaaa aattttttat ttcagcatat taaagtaaaa tctagttacc ttgaaaatga 18000atacagtggg tggttccgta tcaccagtaa gaacataata gtcgaataca gtatccgatt 18060gagattttgc atacaatact agtctagaaa gaaatttgta atcattttct gtgacgggag 18120tccatatatc tgtatcatcg tctagtttat cagtgtccca tgctatattc ctgttatcat 18180cattagttaa tgaaaataac tctcgtgctt cagaaaagtc aaatattgta tccatacata 18240catctccaaa actatcgctt atacgtttat ctttaacgat acctatacct agatggttat 18300ttactaacag acattttcca gatctattga ctataactcc tatagtttcc acatcaacca 18360agtaatgatc atctattgtt atataacaat aacataactc ttttccattt ttatcagtat 18420gtatatctat atcaacgtcg tcgttgtagt gaatagtagt cattgatcta ttatatgaaa 18480cggatatgtc tagaacggca attgttttac gtccagttaa cactttcttt gatttaaagt 18540ctagagtctt tgcaaacata atatccttat ccgactttat atttcctgta gggtggtata 18600attttatttt gcctccacat atcggtgttt ccaaatatat tactagacaa tattccatat 18660agttattagt taagggtacc caattagaac acgtacgctt attatcatca tttggatcgt 18720atttcataaa agttattgta ctatcgatgt caacacattc tacatttttt aatcgtctat 18780atagtatttt tctgatattt tctataatat cagaattgtc ttccatcgga agttgtatac 18840tatcggaatc agttacatgt ttaaataatt ctctgatgtc attccttata caatcaaatt 18900cattattaaa cagtttaata gtctgtagac ctttatcgtc gtaaatatcc attgtcttat 18960tagttacgct tatttttatg tgttttacat tgctttatta tattttataa gaatgattgt 19020ttgacgaatc acgagaacta ttaagacaca ttattaggta tatattataa aaaagttttt 19080gattacgatg ttataagagg aaagaggaca cattaacatc atacatcaat taactacatt 19140cttataacat cgtaatcaaa agaattgcaa ttttgatgta taacaactgt caatgggtta 19200tggaattgta tattacatat tatacggtat gttggtaacg acaaataccg gtcggtaatt 19260gtctgccggt gtaatagaat tatatatata tctatctatt acaccggcct tgtatacata 19320ataataagtt gtggtagtat gatctccata tttataattt aggactttgt attcagtatt 19380tttggaatca taaaaaataa aaaaaagttt tactaattta aaatttaaaa agtatttaca 19440tttttttcac tgtttagtcg cggatatgga attcgatcct gccaaaatca atacatcatc 19500tatagatcat gtaacaatat tacaatacat agatgaacca aatgatataa gactaacagt 19560atgcattatc cgaaatatta ataacattac atattatatc aatatcacaa aaataaatac 19620acatttggct aatcaatttc gggcttggaa aaaacgtatc gccggaaggg actatataac 19680taacttatct agagatacag gaatacaaca atcaaaactt actgaaacta tacgtaactg 19740tcaaaaaaat agaaacatat atggtctata tatacactac aatttagtta ttaatgtggt 19800tattgattgg ataaccgatg tgattgttca atcaatatta agagggttgg taaattggta 19860catagctaat aatacctata cacccaataa tacaacaacc atttctgagt tggatatcat 19920caaaatactg gataaatacg aggacgtgta tagagtaagt aaagaaaaag aatgtggaat 19980ttgctatgaa gttgtttact caaaacgatt agaaaacgat agatactttg gtttattgga 20040ttcgtgtaat catatatttt gcataacatg tatcaatata tggcataaaa cacgaagaga 20100aaccggtgcg tcggataatt gtcctatatg tcgtacccgt tttagaaaca taacaatgag 20160caagttctat aagctagtta actaataaat aaaaagttta atttgttgac gacgtatgtc 20220gttatttttt ctcgtataaa agattaaatt caattcaatt cgttgtttct aatataatct 20280gccgtattgg atggattctc aagacaattg catttagatt atattatcat gaataaaaat 20340agtagcacac aactacttca gcaaatattc ttttttgaaa cgccatctat cgtagtgagg 20400acacaagtga acctataatt atcaaattta ttagtatcag tcacatgaag gactttctgt 20460agagtgacga ttccactatc tgtggtacga acggtttcat cttctttgat gccatcaccc 20520agatgttcta taaacttggt atcctcgtcc gatttcatat cctttgccaa ccaatacata 20580tagctaaact caggcatatg ttccacacat cctgaacaat gaaattctcc agaagatgtt 20640acaatgtcta gatttggaca tttggtttca accgcgttaa catatgagtg aacacaccca 20700tacatgaaag cgatgagaaa taggattctc atcttgccaa aatatcacta gaaaaaattt 20760atttatcaat tttaaaggta taaaaaatac ttattgttgc tcgaatattt tgtatttgat 20820ggtatacgga agattagaaa tgtaggtatt atcatcaact gattctatgg ttttatgtat 20880tctatcatgt ttcactattg cgttggaaat aatatcatat gcttccacat atattttatt 20940ttgttttaac tcataatact cacgtaattc tggattattg gcatatctat gaataatttt 21000agctccatga tcagtaaata ttaatgagaa catagtatta ccacctacca ttattttttt 21060catctcattc aattcttaat tgcaaagatc tatataatca

ttatagcgtt gacttatgga 21120ctctggaatc ttagacgatg tacagtcatc tataatcatg gcatatttaa tacattgttt 21180tatagcatag tcgttatcta cgatgttaga tatttctctc aatgaatcaa tcacataatc 21240taatgtaggt ttatgacata atagcatttt cagcagttca atgtttttag attcgttgat 21300ggcaatggct atacatgtat atccgttatt tgatctaatg ttgacatctg aaccggattc 21360tagcagtaaa gatactagag attgtttatt atatctaaca gccttgtgaa gaagtgtttc 21420tcctcgtttg tcaatcatgt taatgtcttt aagataaggt aggcaaatgt ttatagtact 21480aagaattggg caagcataag acatgtcaca aagacccttt ttgtatgtat aagtgtaaaa 21540attataacat ccatagttgg atttacatag gtgtccaatc gggatctctc catcatcgag 21600ataattgatg gcatctccct tcctttttta gtagatattt catcgtgtaa gaatcaatat 21660taatatttct aaagtatccg tgtatagcct ctttatttac cacagttcca tattccacta 21720gagggatatc gccgaatgtc atatactcaa ttagtatatg ttggaggaca tccgagttca 21780ttgttttcaa tatcaaaaag atggtttcct tatcatttct ccatagtggt acaatactac 21840acattatttc gtgcggcttt ccattttcca aaaacaattt gaccaaatct aaatctacat 21900ctttattgta tctataatca ctatttagat aatcagccat aattcctcga gtgcaacatg 21960ttagatcgtc tatatatgaa taagccgtgt tatctattcc tttcattaac aatttaacga 22020tgtctatatc tatatgagat gacttaatat aatattgaag agctgtacaa tagtttttat 22080ctataaaaga cggcttgatt ccgtgattaa ttagacattt aacaacttcc ggacgcacat 22140atgctctcgt atccgacttt gaatacagat gagagatgat atacagatgc aatacggtac 22200cgcaatttcg tagttgataa tcatcatacg cgtatcagta ctcgtcctca taaagaacac 22260tgcagccatt ttctatgaac aaatcaataa ttttaggaac aggatcattg tcattacata 22320attttctata actgaacgat ggttttcaca tttaacactc aagtcaaatc catgttctac 22380caacaccttt atcaagtcaa cgtctacatt tttggatttc atatagctga atatattaaa 22440gtcatttatg ttgctaaatc cagtggcttc tagtagagcc atcgctatat cctttaactt 22500taacatgtct actatttgtg tattcttcta atggggtagc tgtctccaat ttttgcgtaa 22560tggattagtg ccactgtcta gtagtagttt gacgacctcg acattattac aatgctcatt 22620aaaaaggtat gcgtgtaaag cattattctt gaattggttc ctggtatcat taggatctct 22680gtctctcaac atctgtttaa gttcatcgag agccacctcc tcattttcca aatagtcaaa 22740cattttgact gaatgagcta ctgtgaactc tatacaccca cacaactaat gtcattaaat 22800atcatgtcaa aaacttgtac aattattaat aaaaataatt tagtgtttaa attttaccag 22860ttccagattt tacacctccg ttaatacctc cattaacccc actggacgat cctcctcccc 22920acattccacc gccaccagat gtataagttt tagatccttt attactacca tcatgtccat 22980ggataaagac actccacatg ccgccactac cccctttaga agacatatta ataagactta 23040aggacaagtt taacaataaa attaatcacg agtaccctac taccaaccta cactattata 23100tgattatagt ttctattttt acagtacctt gactaaagtc tctagtcaca agagcaatac 23160taccaaccta cactattata tgattatagt ttctattttt ataggaacgc gtacgagaaa 23220atcaaatgtc taatttctaa cggtagtgtt gataaacgat tatcgtcaat ggatacctcc 23280tctatcatgt cgtctatttt cttactttgt tctattaact tattagcatt atatattatt 23340tgattataaa acttatattg cttattagcc caatctgtaa atatcggatt attaacatat 23400cgtttctttg taggtttatt taacatgtac atcactgtaa gcatgtccgt accatttatt 23460ttaatttgac gcatatccgc aatttctttt tcgcagtcgg ttataaattc tatatatgat 23520ggatacatgc tacatgtgta cttataatcg actaatatga agtacttgat acatattttc 23580agtaacgatt tattattacc acctatgaat aagtacctgt gatcgtctag gtaatcaact 23640gtttttttaa tacattcgat ggttggtaat ttactcagaa taatttccaa tatcttaata 23700tataattctg ctatttctgg gatatattta tctgccagta taacacaaat agtaatacat 23760gtaaacccat attttgttat tatattaatg tctgcgccat tatctattaa ccattctact 23820aggctgacac tatgcgactc aatacaatga taaagtatac tacatccatg tttatctatt 23880ttgtttatat cattaatata cggcttacaa agttttagta tcgataacac atccaactca 23940cgcatagaga aggtagggaa taatggcata atatttatta ggttatcatc attgtcatta 24000tctacaacta agtttccatt ttttaaaata tactcgacaa ctttaggatc tctattgcca 24060aatttttgaa aatatttatt tatatgctta aatctatata atgtagctcc ttcatcaatc 24120atacatttaa taacattgat gtatactgta tgataagata catattctaa caatagatct 24180tgtatagaat ctgtatatct tttaagaatt gtggatatta ggatattatt acgtaaacta 24240ttacacaatt ctaaaatata aaacgtatca cggtcgaata atagttgatc aactatataa 24300ttatcgattt tgtgattttt cttcctaaac tgtttacgta aatagttaga tagaatattc 24360attagttcat gaccactata gttactatcg aataacgcgt caaatatttc ccgtttaata 24420tcgcatttgt caagataata atagagtgtg gtatgttcac gataagtata ataacgcatc 24480tctttttcgt gtgaaattaa atagtttatt acgtccaaag atgtagcata accatcttgt 24540gacctagtaa taatataata atagagaact gttttaccca ttctatcatc ataatcagtg 24600gtgtagtcgt aatcgtaatc gtctaattca tcatcccaat tataatattc accagcacgt 24660ctaatctgtt ctattttgat cttgtatcca tactgtatgt tgctacatgt aggtattcct 24720ttatccaata atagtttaaa cacatctaca ttgggatttg atgttgtagc gtatttttct 24780acaatattaa taccattttt gatactattt atttctatac ctttcgaaat tagtaatttc 24840aataagtcta tatcgatgtt atcagaacat agatattcga atatatcaaa atcattgata 24900tttttatagt cgactgacga caataacaaa atcacgacat cgtttttgat attattattt 24960ttcttggtaa cgtatgcctt taatggagtt tcaccatcat actcatataa tggatttgca 25020ccactttcta tcaatgattg tgcactgctg gcatcgatgt taaatgtttt acaactatca 25080tagagtatct tatcgttaac catgattggt tgttgatgct atcgcatttt ttggtttctt 25140tcatttcagt tatgtatgga tttagcacgt ttgggaagca tgagctcata tgatttcagt 25200actgtagtgt cagtactatt agtttcgatc agatcaatgt ctagatctat agaatcaaaa 25260cacgataggt cagaagataa tgaatatctg tacgcttctt gttgtactgt aacttctggt 25320tttgttagat ggttgcatcg tgctttaacg tcaatggtac aaattttatc ctcgctttgt 25380gtatcatatt cgtccctact ataaaattgt atattcagat tatcatgaga tgtgtatacg 25440ctaacggtat caataaacgg agcacaccat ttagtcataa ccgtaatcca aaaattttta 25500aagtatatct taacgaaaga agttgtgtca ttgtctacgg tgtatggtac tagatcctca 25560taagtgtata tatctagagt aatgtttaat ttattaaatg gttgataata tggatcctca 25620tgacaatttc cgaagatgga aataagacat aaacacgcaa taaatctaat tgcggacatg 25680gttactcctt aaaaaaatac gaataatcac cttggctatt tagtaagtgt catttaacac 25740tatactcata ttaatccatg gactcataat ctctatacgg gattaacgga tgttctatat 25800acggggatga gtagttctct tctttaactt tatacttttt actaatcata tttagactga 25860tgtatgggta atagtgtttg aagagctcgt tctcatcatc agaataaatc aatatctctg 25920tttttttgtt atacagatgt attacagcct catatattac gtaatagaac gtgtcatcta 25980ccttattaac tttcaccgca tagttgtttg caaatacggt taatcctttg acctcgtcga 26040tttccgacca atctgggcgt ataatgaatc taaactttaa tttcttgtaa tcattcgaaa 26100taatttttag tttgcatccg tagttatccc ctttatgtaa ctgtaaattt ctcaacgcga 26160tatctccatt aataatgatg tcgaattcgt gctgtatacc catactgaat ggatgaacga 26220ataccgacgg cgttaatagt aatttacttt ttcatcttta catattgggt actagtttta 26280ctatcataag tttataaatt ccacaagcta ctatggaata agccaaccat cttagtataa 26340cacacatgtc ttaaagttta ttaattaatt acatgttgtt ttatatatat cgctacgaat 26400ttaaacagag aaatcagttt aggaaaaaaa attatctatc tacatcatca cgtctctgta 26460ttctacgata gagtgctact ttaagatgcg acagatctgt gtcatcaaat atatactcca 26520ttaaaatgat tattccggca gcgaacttga tattggatat atcacaacct ttgttaatat 26580ctacgacaat agacagcagt cccatggttc cataaacagt gagtttatct ttctttgaag 26640agatattttg tagagatctt ataaaactgt cgaatgacat cgcatttata tctttagcta 26700aatcgtatat gttaccatcg taatatctaa ccgcgtctat cttaaacgtt tccatcgctt 26760taaagacgtt tccgatagat ggtctcattt catcagtcat actgagccaa caaatataat 26820cgtgtataac atctttgata gaatcagact ctaaagaaaa cgaatcggct ttattatacg 26880cattcatgat aaacttaatg aaaaatgttt ttcgttgttt aagttggatg aatagtatgt 26940cttaataatt gttattattt cattaattaa tatttagtaa cgagtacact ctataaaaac 27000gagaatgaca taactagtta tcaaagtgtc taggacgcgt aattttcata tggtatagat 27060cctgtaagca ttgtctgtat tctggagcta ttttctctat cgcattagtg agttcagaat 27120atgttataaa tttaaatcga ataacgaaca taactttagt aaagtcgtct atattaactc 27180ttttattttc tagccatcgt aataccatgt ttaagatagt atattctcta gttactacga 27240tctcatcgtt gtctagaata tcacatactg aatctacatc caattttaga aattggtctg 27300tgttacatat ctcttctata ttattgttga tgtattgtcg tagaaaacta ttacgtagac 27360cattttcttt ataaaacgaa tatatagtac tccaattatc tttaccgata tatttgcaca 27420cataatccat tctctcaatc actacatctt taagattttc gttgttaaga tatttggcta 27480aactatataa ttctattaga tcatcaacag aatcagtata tatttttcta gatccaaaga 27540cgaactcttt ggcgtcctct ataatattcc cagaaaagat attttcgtgt tttagtttat 27600cgagatctga tctgttcata tacgccatga ttgtacggta cgttatgata accgcataaa 27660ataaaaatcc attttcattt ttaaccaata ctattcataa ttgagattga tgtaatactt 27720tgttactttg aacgtaaaaa cagtacacgg atccgtatct ccaacaagca cgtagtaatc 27780aaatttggtg ttgttaaact tcgcaatatt catcaattta gatagaaact tatactcatc 27840atctgtttta ggaatccatg tattattacc actttccaac ttatcattat cccaggctat 27900gtttcgtcca tcatcgttgc gcagagtgaa taattctttt gtattcggta gttcaaatat 27960atgatccatg catagatcag taaagctatt gtagatgtga tttttcctaa atctaatata 28020aaactcgttt actagcaaac actttcctga tttatcgacc aagacacata tggtttctaa 28080atctatcaag tggtggggat ccatagttat gacgcagtaa catatattat tacattcttg 28140actgtcgcta atatctaaat atttattgtt atcgtattgg attctgcata tagatggctt 28200gtatgtcaaa gatatagaac acataaccaa tttatagtcg cgctttacat tctcgaatct 28260aaagttaaga gatttagaaa acattatatc ctcggatgat gttatcactg tttctggagt 28320aggatatatt aaagtcttta cagatttcgt ccgattcaaa taaatcacta aataatatcc 28380cacattatca tctgttagag tagtatcatt aaatctatta tattttatga aagatatatc 28440actgctcacc tctatatttc gtacattttt aaactgtttg tataatatct ctctgataca 28500atcagatata tctattgtgt cggtagacga taccgttaca tttgaattaa tggtgttcca 28560ttttacaact tttaacaagt tgaccaattc atttctaata gtatcaaact ctccatgatt 28620aaatatttta atagtatcca ttttatatca ctacggacac aaagtagctg acataaacca 28680ttgtataatt tttatgtttt atgtttatta gcgtacacat tttggaagtt ccggcttcca 28740tgtatttcct ggagagcaag tagatgatga ggaaccagat agtttatatc cgtacttgca 28800cttaaagtct acattgtcgt tgtatgagta tgatctttta aacccgctag acaagtatcc 28860gtttgatatt gtaggatgtg gacatttaac aatctgacac gtgggtggat cggaccattc 28920tcctcctgaa cacaggacac tagagttacc aatcaacgaa tatccactat tgcaactata 28980agttacaacg ctcccatcgg tataaaaatc ctcgtatccg ttatgtcttc cgttggatat 29040agatggaggg gattggcatt taacagattc acaaataggt gcctcgggat tccataccat 29100agatccagta gatcctaatt cacaatacga tttagattca ccgatcaaat gatatccgct 29160attacaagag tacgttatac tagagccaaa gtctactcca ccaatatcaa gttggccatt 29220atcgatatct cgaggcgatg ggcatctccg tttaatacat tgattaaaga gtgtccatcc 29280agtacctgta catttagcat atataggtcc cattttttgc tttctgtatc caggtagaca 29340tagatattct atagtgtctc ctatgttgta attagcatta gcatcagtct ccacactatt 29400cttaaatttc atattaatgg gtcgtgacgg aatagtacag catgatagaa cgcatcctat 29460tcccaacaat gtcaggaacg tcacgctctc caccttcata tttatttatc cgtaaaaatg 29520ttatcctgga catcgtacaa ataataaaaa gcccatatat gttcgctatt gtagaaattg 29580tttttcacag ttgctcaaaa acgatggcag tgacttatga gttacgttac actttggagt 29640ctcatcttta gtaaacatat cataatattc gatattacga gttgacatat cgaacaaatt 29700ccaagtattt gattttggat aatattcgta ttttgcatct gctataatta agatataatc 29760accgcaagaa cacacgaaca tctttcctac atggttaaag tacatgtaca attctatcca 29820tttgtcttcc ttaactatat atttgtatag ataattacga gtctcgtgag taattccagt 29880aattacatag atgtcgccgt cgtactctac agcataaact atactatgat gtctaggcat 29940gggagacttt tttatccaac gatttttagt gaaacattcc acatcgttta atactacata 30000tttttcatac gtggtataaa ctccacccat tacatatata tcatcgttta cgaataccga 30060cgcgcctgaa tatctaggag taattaagtt tggaagtctt atccatttcg aagtgccgtg 30120tttcaaatat tctgccacac ccgttgaaat agaaaattct aatcctccta ttacatataa 30180ctttccatcg ttaacacaag tactaacttc tgattttaac gacgacatat tagtaaccgt 30240tttccatttt ttcgtttcaa gatctacccg cgatacggaa taaacatgtc tattgttaat 30300catgccgcca ataatgtata gacaattatg taaaacattt gcattataga attgtctatc 30360tgtattaccg actatcgtcc aatattctgt tctaggagag taatgggtta ttgtggatat 30420ataatcagag tttttaatga ctactatatt atgttttata ccatttcgtg tcactggctt 30480tgtagatttg gatatagtta atcccaacaa tgatatagca ttgcgcatag tattagtcat 30540aaacttggga tgtaaaatgt tgatgatatc tacatcgttt ggatttttat gtatccactt 30600taataatatc atagctgtaa catcctcatg atttacgtta acgtcttcgt gggataagat 30660agttgtcagt tcatcctttg ataattttcc aaattctgga tcggatgtca ccgcagtaat 30720attgttgatt atttctgaca tcgacgcatt atatagtttt ttaattccat atcttttaga 30780aaagttaaac atccttatac aatttgtgaa attaatatta tgaatcatag tttttacaca 30840tagatctact acaggcggaa catcaattat tacggcagca actagtatca tttctacatt 30900gtttatggtg atgtttatct tcttccagcg catatagtct aatagcgatt caaacgcgtg 30960atagtttata ccattcaata taatcgcttc atcctttaga tggtgatcct gaatgcgttt 31020aaaaaaatta tacggagacg ccgtaataat ttccttattc acttgtataa tttccccatt 31080gatagaaaat atcacgcttt ccattcttaa agtactataa gtaattatag tataatgtaa 31140acgtttatat attcaatatt tttataaaaa tcattttgac attaattcct ttttaaattt 31200ccgtctatca tctatagaaa cgtattctat gaatttataa aatgctttta cgtgtcctat 31260cgtaggcgat agaaccgcta aaaagcctat cgaatttcta caaaagaatc tgttatatgg 31320tatagggaga gtataaaaca ttaaatgtcc gtacttatta aagtattcag tagccaatcc 31380taactctttc gaatacttat taatggctct tgttctgtac gaatctattt ttttgaacaa 31440cggacctagt ggtatatctt gttctatgta tctaaaataa tgtctgacta gatccgttag 31500tttaatatcc tcagtcatct tgtctagaat ggcaaatcta actgcgggtt taggctttag 31560tttagtttct atatctacat ctatgtcttt atctaacacc aaaaatataa tagctaatat 31620tttattacaa tcatccggat attcttctac gatctcacta actaatgttt ctttggttat 31680actagtatag tcactatcgg acaaataaag aaaatcagat gatcgatgaa taatacattt 31740aaattcatca tctgtaagat ttttgagatg tctcattaga atattattag ggttagtact 31800cattatcatt aggcagctat tacttatttt attatttttc accatataga tcaatcatta 31860gatcatcaaa atatgtttca atcatcctaa agagtatggt gaatgactct tcccatctaa 31920tttctgaacg ttcaccaatg tctctagcca ctttggcact aatagcgatc attcgcttag 31980cgtcttctat attattaact ggttgattca atctatctag caatggaccg tcggacagcg 32040tcattctcat gttcttaatc aatgtacata catcgccgtc atctaccaat tcatccaaca 32100acataagctt tttaaaatca tcattataat aggtttgatc gttgtcattt ctccaaagaa 32160tatatctaat aagtagagtc ctcatgctta gtaatttaac tattttagtt aacaactatt 32220ttttatgtta aatcaattag tacaccgcta tgtttaatac ttattcatat tttagttttt 32280aggattgaga atcaatacaa aaattaatgc atcattaatt ttagaaatac ttagtttcca 32340cgtagtcaat gaaacatttg aactcatcgt acaggacgtt ctcgtacagg acgtaactat 32400aaaccggttt atatttgttc aagatagata caaatccgat aacttttttt acgaattcta 32460cgggatccac tttaaaagtg tcataccggg ttctttttat ttttttaaac agatcaatgg 32520tgtgatgttg attaggtctt ttacaaattt gatatagaat agcgtttaca tattctccat 32580aatggtcaat cgccatttgt tcgtatgtca taaattcttt aattatatga cactgtgtat 32640tatttagttc atccttgttc attgttagga atctatccaa aatggcaatt atactagaac 32700tataggtgcg ttgtatacac atattgatgt gtctgtttat acaatccatg atatttggat 32760ccatgctact accttcgggt aaaattgtag catcatatac catttctagt actttaggtt 32820cattattatc cattgcagag gacgtcatga tcgaatcata aaaaaatata ttatttttat 32880gttattttgt taaaaataat catcgaatac ttcgtaagat actccttcat gaacataatc 32940agttacaaaa cgtttatatg aagtaaagta tctacgattt ttacaaaagt ccggatgcat 33000aagtacaaag tacgcgataa acggaataat aatagattta tctagtctat ctttttctat 33060agctttcata gttagataca tggtctcaga agtaggatta tgtaacatca gcttcgataa 33120aatgactggg ttatttagtc ttacacattc gctcatacat gtatgaccgt taactacaga 33180gtctacacta aaatgattga acaatagata gtctaccatt gtttcgtatt cagatagtac 33240agcgtagtac atggcatctt cacaaattat atcattgtct aatagatatt tgacgcatct 33300tatggatccc acttcaacag ccatcttaaa atcggtagaa tcatattgct ttcctttatc 33360attaataatt tctagaacat catctctatc ataaaagata caaatattaa ctgtttgatc 33420cgtaataaca ttgctagtcg atagcaattt gttaataaga tgcgctgggc tcaatgtctt 33480aataagaagt gtaagaggac tatctccgaa tttgttttgt ttattaacat ccgttgatgg 33540aagtaaaaga tctataatgt ctacattctt gactgtttta gagcatacaa tatggagagg 33600tgtatttcca tcatgatctg gttttgaggg actaattcct agtttcatca tccatgagat 33660tgtagaagct tttggattgt ctgacataag atgtctatga atatgatttt tgccaaattt 33720atccactatc ctggcttcga atccgatgga cattattttt ttaaacactc tttctgaagg 33780atctgtacac gccaacaacg gaccacatcc ttcttcatca accgagttgt taatcttggc 33840tccatactgt accaataaat ttattctctc tatgacttca tcatctgttc ccgagagata 33900atatagaggc gttttatgct gtttatcaca cgcgtttgga tctgcgccgt gcgtcagcag 33960catcgcgact attctattat tattaatttt agaagctata tgcaatggat aatttccatc 34020atcatccgtc tcatttggag agtatcctct atgaagaagt tcttcgacaa atcgttcatc 34080tagtccttta attccacaat acgcatgtag aatgtgataa ttatttccag aaggttcgat 34140agcttgtagc atattcctaa atacatctaa atttttacta ttatatttgg cataaagaga 34200tagataatac tcggccgaca taatgttgtc cattgtagta taaaaattaa tatttctatt 34260tctatttctg tatatttgca acaatttact ctctataaca aatatcataa cttagttctt 34320ttatgtcaag aaggcactgg tttagttcat ctataaatgt cacgccataa ctaccacgca 34380tgccatactc agaattatga taaagatatt tatccttggg gtgtaggtaa tggggattaa 34440tctttgttgg atcagtctct aagttaacac atgtcacaca tgatccattt atagttatat 34500cacacgatga tgatttatga attgattccg gaagatcgct atcgtatttt gtggttccac 34560aattcatttc catacatgtt attgtcacac taatattatg atgaacttta tctagccgct 34620gagtggtaaa caacagaaca gatagtttat tatctttacc aacaccctca gccgctgcca 34680caaatctctg atccgtatcc atgatggtca tgtttatttc tagtccgtat ccagtcaaca 34740ctatgttagc atttctgtcg atatagcttt cactcatatg acactcacca ataatagtag 34800aattaatgtc gtaatttaca ccaatagtga gttcggcggc aaagtaccaa taccggtaat 34860cttgtcgagg aggacatata gtattcttgt attctaccga atacccgaga gatgcgatac 34920aaaagagtaa gactaatttg taaaccatct tactcaaaat atgtaacaat agtacgatgc 34980aatgagtaag acaataggaa atctatctta tatacacata attattctat caattttacc 35040aattagttag tgtaatgtta acaaaaatgt gggagaatct aattagtttt tctttacaca 35100attgacgtac atgagtttga gttccttgtt tttgctaatt atttcatcca atttattatt 35160cttgacgata tcgagatctt ttgtatagga gtcagacttg tattcaacat gcttttctat 35220aatcatttta gctatttcgg catcatccaa tagtacattt tccagattag cagaatagat 35280attaatgtcg tatttgaaca gagcctgtaa catctcaatg tctttattat ctatagccaa 35340tttaatgtcc ggaatgaaga gaagggaatt attggtgttt gtcgacgtca tatagtcgag 35400caagagaatc atcatatcca cgtgtccatt ttttatagtg atgtgaatac aactaaggag 35460aatagccaga tcaaaagtag atggtatctc tgaaagaaag taggaaacaa tacttacatc 35520attaagcatg acggcatgat aaaatgaagt tttccatcca gttttcccat agaacatcag 35580tctccaattt ttcttaacaa acagttttac cgtttgcatg ttaccactat caaccgcata 35640atacaatgca gtgtttccct tgtcatcaaa ttgtgaatca tccagtccac tgaatagcaa 35700aatctttact attttagtat cttccaatgt ggctgcctga tgtaatggaa attcattctc 35760tagaagattt ttcaatgctc cagcgttcaa caacgtacat actagacgca cgttattatc 35820agctattgca taatacaagg cactatgacc gttgatatcc gccttaaatg catctttgct 35880agagagaaag cttttcagct gcttagactt ccaagtatta attcgtgaca gatccatgtc 35940tgaaacaaga cgctaattag tgtatatttt ttcatttttt ataattttgt catattgcac 36000cagaattaat aatatctcta atagatctga ttagtagata catggctatc gcaaaacaac 36060atatacacat ttaataaaaa taatatttat taagaaaatt cagatttcac gtacccatca 36120atataaataa aataatgatt ccttacaccg tacccatatt

aaggagattc caccttaccc 36180ataaacaata taaatccagt aatatcatgt ctgatgatga acacaaatgg tgtattaaat 36240tccagttttt caggagatga tctcgccgta gctaccataa tagtagatgc ctctgctaca 36300gttccttgtt cgtcgacatc tatctttgca ttctgaaaca ttttataaat atataatggg 36360tccctagtca tatgtttaaa cgacgcatta tctggattaa acatactagg agccatcatt 36420tcggctatcg acttaatatc cctcttattt tcgatagaaa atttagggag tttaagattg 36480tacactttat tccctaattg aaacgaccaa tagtctaatt ttgcagccgt gatagaatct 36540gtgaaatggg tcatattatc acctattgcc aggtacatac taatattagc atccttatac 36600ggaaggcgta ccatgtcata ttctttgtca tcgattgtga ttgtatttcc ttgcaattta 36660gtaactacgt tcatcatggg aaccgttttc gtaccgtact tattagtaaa actagcattg 36720cgtgttttag tgatatcaaa cggatattgc catatacctt taaaatatat agtattaatg 36780attgcccata gagtattatt gtcgagcata ttagaatcta ctacattaga cataccggat 36840ctacgttcta ctatagaatt aattttatta accgcatctc gtctaaagtt taatctatat 36900aggccgaatc tatgatattg ttgataatac gacggtttaa tacacacagt attatctacg 36960aaactttgat aagttagatc agtgtacgta tatttagatg ttttcagctt agctaatcct 37020gatattaatt ctgtaaatgc tggacccaga tctctttttc tcaaatccat agtcttcaat 37080aattctattc tagtattacc tgatgcaggc aatagcgaca taaacataga aaacgaataa 37140ccaaacggtg agaagacaat attatcatct tgaatatttt tatacgctac tataccggca 37200ttggtaaatc cttgtagacg ataggcggac gctgaacacg ctaacgatag tatcaataac 37260gcaatcatga ttttatggta ttaataatta accttatttt tatgttcggt ataaaaaaat 37320tattgatgtc tacacatcct tttgtaattg acatctatat atccttttgt ataatcaact 37380ctaatcactt taacttttac agttttccct accagtttat ccctatattc aacatatcta 37440tccatatgca tcttaacact ctctgccaag atagcttcag agtgaggata gtcaaaaaga 37500taaatatata gagcataatc attctcgtat actctgccct ttattacatc acccgcattg 37560ggcaacgaat aacaaaatgc aagcatcttg ttaacgggct cgtaaattgg gataaaaatt 37620atgtttttat tgtcttatat ctattttatt caagagaata ttcaggaatt tctttttccg 37680gttgtatctc atcgcagtat atatcatttg tacattgttt tatatttttt aatagtttac 37740accttttagt aggactagta tcgtacaatt catagctgta ttttgaattc caatcacgca 37800taaaaatatc ttccaattgt tgacgaagac ctaatccatc atccggtgta atattaatag 37860atgctccaca tgtatccgta aagtaatttc ctgtccaatt tgaggtacct atataggccg 37920ttttatcggt taccatatat ttggcatggt ttaccctaga atacggaatg ggaggatcag 37980catctggtac aataaatagc tttacttcta tatttatgtt tttagatttt agcatagcga 38040tagatcttaa aaagtttctc atgataaacg aagatcgttg ccagcaacta atcaatagct 38100taacggatac ttgtctgtct atagcggatc ttcttaattc atcttctata taaggccaaa 38160acaaaatttt acccgccttc gaataaataa tagggataaa gttcataaca gatacataaa 38220cgaatttact cgcatttcta atacatgaca ataaagcggt taaatcattg gttctttcca 38280tagtacatag ttgttgcggc gcagaagcaa taaatacaga gtgtggaacg ccgcttacgt 38340taatactaag aggatgatct gtattataat acgacggata aaagtttttc caattatatg 38400gtagattgtt aactccaaga taccagtata cctcaaaaat ttgagtgaga tccgctgcca 38460agttcctatt attgaagatc gcaataccca attctttgac ctgagttagt gatctccaat 38520ccatgttagc gcttcctaaa taaatatgtg tattatcaga tatccaaaat tttgtatgaa 38580gaactcctcc taggatattt gtaatatcta tgtatcgtac ttcaactccg gccatttgta 38640gtctttcaac atcctttaat ggtttgttag atttattgac ggctactcta actcgtactc 38700ctcttttggg taattgtaca atctcgttta atattatcgt gccgaaattc gtacccactt 38760catccgataa actccaataa aaagatgata tatctagtgt ttttgtggta ttggatagaa 38820tttccctcca catgttaaat gtagacaaat atactttatc aaattgcata cctataggaa 38880tagtctctgt aatcactgcg attgtattat ccggattcat tttatttgtt aaaaaataat 38940cctatatcac ttcactctat taaaaatcca agtttctatt tctttcatga ctgatttttt 39000aacttcatcc gtttccttat gaagatgatg tttggcacct tcataaattt ttatttctct 39060attacaattt gcatgttgca tgaaataata tgcacctaaa acatcgctaa tcttattgtt 39120tgttccctgg agtatgagag tcggggggtg ttaatcttgg aaattatttt tctaaccttg 39180ttggtagcct tcaagacctg actagcaaat ccagccttaa ttttttcatg attgactaat 39240gggtcgtatt ggtatttata aacttcatcc atatctctag atactgattc tggacatagc 39300tttccgactg gcgcatttgg tgtgatggtt cccataagtt tggcagctag cagattcagt 39360cttgaaacag catctgcatt aactagagga gacattagaa tcattgctgt aaacaagttt 39420ggattatcgt aagaggctag ctcccatgga atgacccaat aagtagattt aatagttacc 39480acgtgctgta ccaaagtcat caatcatcat tttttcacca ttacttcttc catgtccaat 39540atgatcatgt gagaatacta aaattcctaa cgatgatatg ttttcagcta gttcgtcata 39600acgtccagaa tgtttaccag ctccatgact tataaatact aatgccttag gatatgtaat 39660aggtttccaa tatttacaat atatgtaatc attgtccaga ttgaacatac agtttgcact 39720catgattcac gttatataac tatcaatatt aacagttcgt ttgatgatca tattattttt 39780atgttttatt gataattgta aaaacataca attaaatcaa tatagaggaa ggagacggct 39840actgtctttt gtgagatagt catggcgact aaattagatt atgaggatgc tgttttttac 39900tttgtggatg atgataaaat atgtagtcgc gactccatca tcgatctaat agatgaatat 39960attacgtgga gaaatcatgt tatagtgttt aacaaagata ttaccagttg tggaagactg 40020tacaaggaat tgatgaagtt cgatgatgtc gctatacggt actatggtat tgataaaatt 40080aatgagattg tcgaagctat gagcgaagga gaccactaca tcaattttac aaaagtccat 40140gatcaggaaa gtttattcgc taccatagga atatgtgcta aaatcactga acattgggga 40200tacaaaaaga tttcagaatc tagattccaa tcattgggaa acattacaga tctgatgacc 40260gacgataata taaacatctt gatacttttt ctagaaaaaa aattgaattg atgatatagg 40320ggtcttcata acgcataatt attacgttag cattctatat ccgtgttaaa aaaaattatc 40380ctatcatgta tttgagagtt ttatatgtag caaacatgat agctgtgatg ccaataagct 40440ttagatattc acgcgtgcta gtgttaggga tggtattatc tggtggtgaa atgtccgtta 40500tataatctac aaaacaatca tcgcatatag tatgcgatag tagagtaaac atttttatag 40560tttttactgg attcatacat cgtctaccca attcggttat aaatgaaatt gtcgccaatc 40620ttacacccaa ccccttgtta tccattagta tagtattaac ttcgttattt atgtcataaa 40680ctgtaaatga ttttgtagat gccatatcat acatgatatt catgtcccta ttataatcat 40740tactaacttt atcacaatat atgttgataa tatctatata tgatctagtc tttgtgggca 40800actgtctata caagtcgtct aaacgttgtt tactcatata gtatcgaaca gccatcatta 40860catggtcccg tttcgttgat agataatcga gtatgttagt ggacttgtca aatctatata 40920ccatattttc tggaagtgga tatacatagt cgtgatcaac attattgcta gcctcatctt 40980ctatatcctg tactatacca ttatctatat catctacata atctacgata ttattacaca 41040taaacatcga caacatacta ttgtttatta tctaagtcct gttgatccaa acccttgatc 41100tcctctattt gtactatcta gagattgtac ttcttccagt tctggataat atatacgttg 41160atagattagc tgagctattc tatctccagt atttacatta aacgtacatt ttccattatt 41220aataagaatg actcctatgt ttcccctata atcttcgtct attacaccac ctcctatatc 41280aatgcctttt agtgacagac cagacctagg agctattcta ccatagcaaa tcttaggcat 41340ggacatacta atatctgtct taattaactg tctttctcct ggagggatag tataatcgta 41400agcgctatac aaatcatatc cggcagcacc cggcgattgc ctagtaggag atttagctct 41460gttagtttcc ttaacaaatc taactggtga gttaatattc atgttgaaca taaaactaat 41520attttatttc aaaattattt accatcccat atattccatg aataagtgtg atgattgtac 41580acttctatag tatctatata cgattcacga taaaatcctc ctatcaatag cagtttatta 41640tccactatga tcaattctgg attatccctc ggataaatag gatcatctat cagagtccat 41700gtattgctgg attcacaata aaattccgca tttctaccaa ccaagaataa ccttctaccg 41760aacactaacg cgcatgattt ataatgagga taataagtgg atggtccaaa ctgccactga 41820tcatgattgg gtagcaaata ttctgtagtt gtatcagttt cagaatgtcc tcccattacg 41880tatataacat tgtttataga tgccactgct ggattacatc taggtttcag aagactcggc 41940atattaaccc aagcagcatc cccgtggaac caacgctcaa cagatgtggg atttggtaga 42000cctcctacta cgtataattt attgttagcg ggtatcccgc tagcatacag tctggggcta 42060ttcatcggag gaattggaat ccaattgttt gatatataat ttacagctat agcattgtta 42120tgtatttcat tgttcatcca tccaccgatg agatatacta cttctccaac atgagtactt 42180gtacacatat ggaatatatc tataatttga tccatgttca taggatactc tatgaatgga 42240tacttgtatg atttgcgtgg ttgtttatca caatgaaata ttttggtaca gtctagtatc 42300cattttacat tatttatacc tctgggagaa agataatttg acctgattac atttttgata 42360aggagtagca gatttcctaa tttatttctt cgcctcatat accacttaat gacaaaatca 42420actacataat cctcatctgg aacatttagt tcatcgcttt ctagaataag tttcatagat 42480agataatcaa aattgtctat gatgtcatct tccagttcca aaaagtgttt ggcaataaag 42540tttttagtat gacataagag attggatagt ccgtattcta tacccatcat gtaacactcg 42600acacaatatt cctttctaaa atctcgtaag ataaagttta tacaagtgta gatgataaat 42660tctacagagg ttaatataga agcacgtaat aaattgacga cgttatgact atctatatat 42720acctttccag tatatgagta aataactata gaagttaaac tgtgaatgtc aaggtctaga 42780caaaccctcg taactggatc tttatttttc gtgtattttt gacgtaaatg tgtgcgaaag 42840taaggagata actttttcaa tatcgtagaa ttgactatta tattgcctcc tatggcatca 42900ataattgttt tgaatttctt agtcatagac aatgctaata tattcttaca gtacacagta 42960ttgacaaata tcggcattta tgtttcttta aaagtcaaca tctagagaaa aatgattatc 43020tttttgagac ataactccca ttttttggta ttcacccaca cgtttttcga aaaaattagt 43080ttttccttcc aatgatatat tttccatgaa atcaaacgga ttggtaacat tataaatttt 43140tttaaatccc aattcagaaa tcaatctatc cgcgacgaat tctatatatg ttttcatcat 43200ttcacaattc attcctataa gtttaactgg aagagccgca gtaagaaatt cttgttcaat 43260ggatactgca tctgttataa tagatctaac ggtttcttca ctcggtggat gcaataaatg 43320tttaaacatc aaacatgcga aatcgcagtg cagaccctcg tctctactaa ttagttcgtt 43380ggaaaacgtg agtccgggca ttaggccacg ctttttaagc caaaatatgg aagcgaatga 43440tccggaaaag aagattcctt ctactgcagc aaaggcaata agtctctctc cataaccggc 43500gctgtcatgt atccactttt gagcccaatc ggccttcttt tttacacaag gcatcgtttc 43560tatggcatta aagagatagt ttttttcatt actatcttta acataagtat cgatcaaaag 43620actatacatt tccgaatgaa tgttttcaat ggccatctga aatccgtaga aacatctagc 43680ctcggtaatc tgtacttctg tacaaaatcg ttccgccaaa ttttcattca ctattccgtc 43740actggctgca aaaaacgcca atacatgttt tataaaatat ttttcgtctg gtgttagttt 43800attccaatca ttgatatctt tagatatatc tacttcttcc actgtccaaa atgatgcctc 43860tgccttttta tacatgttcc agatgtcatg atattggatt gggaaaataa caaatctatt 43920tggatttggt gcaaggatgg gttccataac taaattaaca ataacaataa attttttttc 43980agttatctat atgcctgtac ttggatcttt tgtacatcga tatcgccgca atcactacaa 44040taattacaag tattattgat agcattgtta ttagtactat cataattaaa ttatctacat 44100tcatgggtgc tgaataatcg ttattatcat cattatcatt ttgtaattgt gacatcatac 44160tagataaatc gtttgcgaga ttgttgtggg aagcgggcat ggaggatgca ttatcattat 44220tatttaacgc cttccatttg gattcacaaa tgttacgcac attcaacatt ttatggaaac 44280tataattttg tgaaaacaga taacaagaaa actcgtcatc gttcaaattt ttaacgatag 44340taaaccgatt aaacgtcgag ctaatttcta acgctagcga ctctgttgga tatgggtttc 44400cagatatata tcttttcagt tcccctacgt atctataatc atctgtagga aatggaagat 44460atttccattt atctactgtt cctaatatca tatgtggtgg tgtagtagaa ccattaagcg 44520cgaaagatgt tatttcgcat cgtattttaa cttcgcaata atttctggtt agataacgca 44580ctctaccagt caagtcaatg atattagcct ttacagatat attcatagta gtcgtaacga 44640tgactccatc ttttagatgc gatactcctt tgtatgtacc agaatcttcg tacctcaaac 44700tcgatatatt taaacaagtt aatgagatat taacgcgttt tatgaatgat gatatataac 44760cagaagtttt atcctcggtg gctagcgcta taaccttatc attataatac caactagtgt 44820gattaatatg tgacacgtca gtgtgggtac aaatatgtac attatcgtct acgtcgtatt 44880cgatacatcc gcatacagcc aacaaatata aaatgacaaa tactctaacg acgttcgtac 44940ccatcttgat gcggtttaat aaatgttttg atttcaattt attgtaaaaa aagattcggt 45000tttatactgt tcgatattct cattgcttat attttcatct atcatctcca cacagtcaaa 45060tccgtggtta gcatgcacct catcaaccgg taaaagacta tcggactctt ctatcattat 45120aactctagaa tatttaattt ggtcattatt aatcaagtca attatcttat ttttaacaaa 45180cgtgagtatt ttactcattt tttataaaaa cttttagaaa tatacagact ctatcgtgtg 45240tctatatctt ctttttatat ccaatgtatt tatgtctgat ttttcttcat ttatcatata 45300taatggtcca aattctacac gtgcttcgga ttcatccaga tcattaaggt tcttataatt 45360gtaacatcct tctcttccct cttctacatc ttccttctta ttcttattct tagcgtcaca 45420gaatctacca cagcaggatc ccatgacgag cgtcatatta aactaatcca ttttcaatta 45480taatatatga ttagtaatga ccattaaaat aaaaaatatt cttcataacc ggcaagaaag 45540tgaaaagttc acattgaaac tatgtcagta gtatacatca tgaaatgaga tgaaatgaga 45600tgaaatgatg atatatatac tctattttgg tggaggatta tatgatataa ttcgtggata 45660atcattttta agacacattt ctttattcgt aaatcttttc acgttaaatg agtgtccata 45720ttttgcaatt tcttcatatg atggcggtgt acgtggacga ggctgctcct gttcttgttg 45780tagtcgccga ctgtcgtgtc tgcgtttaga tccctccatt atcgcgattg cgtagatgga 45840gtactattat ataccttgta attaaatttt tttattaatt aaacgtataa aaacgttccg 45900tatctgtatt taagagccag atttcgtcta atagaacaaa tagctacagt aaaaataact 45960agaataattg ctacacccac tagaaaccac ggatcgtaat acggcaatcg gttttcgata 46020ataggtggaa cgtatatttt atttaaggac ttaacaattg tctgtaaacc acaatttgct 46080tccgcggatc ctgtattaac tatctgtaaa agcatatgtt gaccgggcgg agccgaacat 46140tctccgatat ctaatttctg tatatctata atattattaa cctccgcata cgcattacag 46200ttcttttcta gcttggatac cgcactaggt acatcgtcta gatctattcc tatttcctca 46260gcgatagctc ttctatcctt ttccggaagc aatgaaatca cttcaataaa tgattcaacc 46320atgagtgtga aactaagtcg agaattactc atgcatttgt tagttattcg gagcgcgcaa 46380tttttaaact gtcctataac ctctcctata tgaatagcac aagtgacatt agtagggata 46440gaatgttgag ctaatttttg taaataacta tctataaaaa gattatacaa agttttaaac 46500tctttagttt ccgccattta tccagtctga gaaaatgtct ctcataataa atttttccaa 46560gaaactaatt gggtgaagaa tggaaacctt taatctatat ttatcacagt ctgtcttggt 46620acacatgatg aattcttcta atgccgtact aaattcgata tctttttcga tttctggata 46680tgtttttaat aaagtatgaa caaagaaatg gaaatcgtaa taccagttat gttcaacttt 46740gaaattgttt tttattttct tgttaatgat tccagccact tgggaaaagt caaagtcgtt 46800taatgccgat ttaatacgtt cattaaaaac aaacttttta tcctttagat gaattattat 46860tggttcattg gaatcaaaaa gtaagatatt atcgggttta agatctgcgt gtaaaaagtt 46920gtcgcagcat ggtagttcgt aaattttaat gtataacaga gccatctgta aaaagataaa 46980ctttatgtat tgtaccaaag atttaaatcc taatttgata gctagctcgg tatctacttt 47040atctgccgaa tacagtgcta ggggaaaaat tataatgttt cctctttcat attcgtagtt 47100agttctcttt tcatgttcga aaaagtgaaa catgcggtta aaatagttta taacattaat 47160attactgtta ataactgccg gataaaagtg ggatagtaat ttcacgaatt tgatactgtc 47220ctttctctcg ttaaacgcct ttaaaaaaac tttagaagaa tatctcaatg agagttcctg 47280accatccata gtttgtatca ataatagcaa catatgaaga acccgtttat acagagtatg 47340taaaaatgtt aatttatagt ttaatcccat ggcccacgca cacacgatta attttttttc 47400atctcccttt agattgttgt atagaaattt gggtactgtg aactccgccg tagtttccat 47460gggactatat aattttgtgg cctcgaatac aaattttact acatagttat ctatcttaaa 47520gactatacca tatcctcctg tagatatgtg ataaaaatcg tcgtttatag gataaaatcg 47580tttatccttt tgttggaaaa aggatgaatt aatgtaatca ttctcttcta tctttagtag 47640tgtttcctta ttaaaattct taaaataatt taacaatcta actgacggag cccaattttg 47700gtgtaaatct aattgggaca ttatattgtt aaaatacaaa cagtctccta atataacagt 47760atctgataat ctatggggag acatccattg atattcaggg gatgaatcat tggcaacacc 47820catttattgt acaaaaagcc ccaatttaca aacgaaagtc caggtttgat agagacaaac 47880aattaactat tttgtctctg tttttaacac ctccacagtt tttaatttct ttagtaatga 47940aattattcac aatatcagta tcttctttat ctaccagaga ttttactaac ttgataacct 48000tggctgtctc attcaatagg gtagtaatat ttgtatgtgt gatattgata tctttttgaa 48060ttgtttcttt tagaagtgat tctttgatgg tgccagcata cgaattacaa taatgcagaa 48120actcggttaa catgcaggaa ttatagtaag ccaattccaa ttgttgcctg tgttgtatta 48180gagtgtcaat atgagcaatg gtgtccttgc gtttctctga tagaatgcga gcagcgattt 48240tggcgttatc atttgacgat atttctggaa tgacgaatcc tgtttctact aactttttgg 48300taggacaaag tgaaacaatc aagaagatag cttctcctcc tatttgtgga agaaattgaa 48360ctcctctaga tgatctactg acgatagtat ctccttgaca gatattggac cgaattacag 48420aagtacctgg aatgtaaagc cctgaaaccc cctcattttt taagcagatt gttgccgtaa 48480atcctgcact atgcccaaga tagagagctc ctttggtgaa tccatctcta tgtttcagtt 48540taaccaagaa acagtcagct ggtctaaaat ttccatctct atctaataca gcatctaact 48600tgatgtcagg aactatgacc ggtttaatgt tatatgtaac attgagtaaa tccttaagtt 48660cataatcatc actgtcatca gttatgtacg atccaaacaa tgtttctacc ggcatagtgg 48720atacgaagat gctatccatc agaatgtttc cctgattagt attttctata tagctattct 48780tctttaaacg attttccaaa tcagtaacta tgttcatttt tttaggagta ggacgcctag 48840ccagtatgga agaggatttt ctagatcctc tcttcaacat ctttgatctc gatggaatgc 48900aaaaccccat agtgaaacaa ccaacgataa aaataatatt gtttttcact ttttataatt 48960ttaccatctg actcatggat tcattaatat ctttataaga gctactaacg tataattctt 49020tataactgaa ctgagatata tacaccggat ctatggtttc cataattgag taaatgaatg 49080ctcggcaata actaatggca aatgtataga acaacgaaat tatactagag ttgttaaagt 49140taatattttc tatgagctgt tccaataaat tatttgttgt aactgcgttc aagtcataaa 49200tcatcttgat actatccagt aaaccgtttt taagttctgg aatattatca tcccattgta 49260aagcccctaa ttcgactatc gaatatcctg ctctgatagc agtttcaata tcgacggacg 49320tcaatactgt aataaaggtg gtagtattgt catcatcgtg ataaactact ggaatatggt 49380cgttagtagg tacggtaact ttacacaacg cgatatataa ctttcctttt gtaccatttt 49440taacgtagtt gggacgtcct gcagggtatt gttttgaaga aatgatatcg agaacagatt 49500tgatacgata tttgttggat tcctgattat tcactataat ataatctaga cagatagatg 49560attcgataaa tagagaaggt atatcgttgg taggataata catccccatt ccagtattct 49620cggatactct attgatgaca ctagttaaga acatgtcttc tattctagaa aacgaaaaca 49680tcctacatgg actcattaaa acttctaacg ctcctgattg tgtctcgaat gcctcgtaca 49740aggatttcaa ggatgccata gattctttga ccaacgattt agaattgcgt ttagcatctg 49800atttttttat taaatcgaat ggtcggctct ctggtttgct accccaatga taacaatagt 49860cttgtaaaga taaaccgcaa gaaaatttat acgcatccat ccaaataacc ctagcaccat 49920cggatgatat taatgtatta ttatagattt tccatccaca attattgggc cagtatactg 49980ttagcaacgg tatatcgaat agattactca tgtaacctac tagaatgata gttcgtgtac 50040tagtcataat atctttaatc caatctaaga aatttaaaat tagatttttt acactgttaa 50100agttaacaaa agtattaccc ggatacgtgg atatcatata tggcattggt ccattatcag 50160taatagctcc ataaactgat acggcgatgg tttttatatg tgtttgatct aacgaggaag 50220aaattcgcgc ccacaattca tctctagata tgtatttaat atcaaacggt aacacatcaa 50280tttcgggacg cgtatatgtt tctaaatttt taatccaaat ataatgatga cctatatgcc 50340ctattatcat actgtcaact atagtacacc tagggaactt acgatacatc tgtttcctgt 50400aatcgttaaa ttttacaaat ctataacatg ctaaaccttt tgacgacaac cattcattaa 50460tttctgatat ggaatctgta ttctcaatac cgtatcgttc taaagctagt gctatatctc 50520cctgttcgtg ggaacgcttt cgtataatat cgatcaacgg ataatctgaa gtttttggag 50580aataatatga ctcatgatct atttcgtcca taaacaatct agacatagga attggaggcg 50640atgatcttaa ttttgtgcaa tgagtcgtca atcctataac ttctaatctt gtaatattca 50700tcatcgacat aatactatct atgttatcat cgtatattag tataccacgg ccttcttcat 50760ttcgtgccaa aatgatatac agtcttaaat agttacgcaa tatctcaata gtttcataat 50820tgttagctgt tttcatcaag atttgtaccc tgtttaacat gatggcgttc tataacgtct 50880ctattttcta tttttaattt tttaaatttt taacgattta ctgtggctag atacccaatc 50940tctctcaaat atttttttag cctcgcttac aagctgttta tctatactat taaaactgac 51000gaatccgtga ttttggtaat gggttccgtc gaaatttgcc gaagtgatat gaacatattc 51060gtcgtcgact atcaacaatt ttgtattatt ctgaatagtg aaaaccttca cagatagatc 51120attttgaaca cacaacgcat ctagactttt ggcggttgcc atagaatata cgtcgttctt 51180atcccaatta ccaactagaa gtctgatctt aactcctcta

ttaatggctg cttctataat 51240ggagttgtaa atgtcgggcc aatagtagct attaccgtcg acacgtgtag tgggaactat 51300ggccaaatgt tcaatatcta tactagtctt agccgacttg agtttatcaa taactacatc 51360ggtatctaga tctctagaat atcccaatag gtgttccgga gaatcagtaa agaacactcc 51420acctatagga ttcttaatat gatacgcagt gctaactggc aaacaacaag ccgcagagca 51480taaattcaac catgaatttt ttgcgctatt aaaggcttta aaagtatcaa atcttctacg 51540aagatctgtg gccagcgggg gataatcaga atatacacct aacgttttaa tcgtatgtat 51600agatcctcca gtaaatgacg cgtttcctac ataacatctt tcatcatctg acacccaaaa 51660acaaccgagt agtagtccca cattattttt tttatctata ttaacggtta taaaatttat 51720atccgggcag tgactttgta gctctcccag atttcttttc cctcgttcat ctagcaaaac 51780tattatttta atcccttttt cagatgcctc ttttagttta tcaaaaataa gcgcgcccct 51840agtcgtactc agaggattac aacaaaaaga tgctatgtat atatatttct tagctagagt 51900gataatttcg ttaaaacatt caaatgttgt caaatgatcg gatctaaaat ccatattttc 51960tggtagtgtt tctaccagcc tacattttgc tcccgcaggt accgatgcaa atggccacat 52020ttagttaaca taaaaactta tacatcctgt tctatcaacg attctagaat atcatcggct 52080atatcgctaa aattttcatc aaagtcgaca tcacaaccta actcagtcaa tatattaaga 52140agttccatga tgtcatcttc gtctatttct atatccgtat ccattgtaga ttgttgaccg 52200attatcgagt ttaaatcatt actaatactc aatccttcag aatacaatct gtgtttcatt 52260gtaaatttat aggcggtgta tttaagttgg tagattttca attatgtatt aatatagcaa 52320cagtagtttt tgctcctcct tgattctagc atcctcttca ttattttctt ctacgtacat 52380aagcatgtcc aatacgttag acaacacacc gacgatggcg gccgccacag acacgaatat 52440gactaaaccg atgaccattt aaaaacccct ctctagcttt cacttaaact gtatcgatca 52500ttcttttagc acatgtataa tataaaaaca ttattctatt tcgaatttag gcttccaaaa 52560atttttcatc cgtaaaccga taataatata tatagacttg ttaatagtcg gaataaatag 52620attaatgctt aaactatcat catctccacg attagagata caatatttac attctttttg 52680ctgtttcgaa actttatcaa tacacgttaa tacaaaccca ggaaggagat attgaaactg 52740aggctgttga aaatgaaacg gtgaatacaa taattcagat aatgtaaaat catgattccg 52800tattctgatg atattagaac tgctaatgga tgtcgatggt atgtatctag gagtatctat 52860tttaacaaag catcgatttg ctaatataca attatcattt tgattaattg ttattttatt 52920catattctta aaaggtttca tatttatcaa ttcttctaca ttaaaaattt ccatttttaa 52980tttatgtagc cccgcaatac tcctcattac gtttcatttt ttgtctataa tatccatttt 53040gttcatctcg gtacatagat tatccaattg agaagcgcat ttagtagttt tgtacatttt 53100aagtttattg acgaatcgtc gaaaactagt tatagttaac attttattat ttgataccct 53160gatattaata cccctgccgt tactattatt tataactgat gtaacccacg taacattaga 53220attaattatc gatagtaatg catcaacgct tccaaaattg tctattataa actcaccgat 53280aattttttta ttgcatgttt tcatattcat taggattatc aaatctttaa tcttattacg 53340attgtatgcg ttgatattac aagacgtcat tctaaaagac ggaggatttc catcaaatgc 53400cagacaatca cgtacaaagt acatggaaat aggttttgtt ctattgcgca tcatagattt 53460atatagaaca cccgtagaaa tactaatttg ttttactcta taaaatacta atgcatctat 53520ttcatcgttt tgtataacgt ctttccaagt gtcaaattcc aaattttttt cattgatagt 53580accaaattct tctatctctt taactacttg catagatagg taattacagt gatgcctaca 53640tgccgttttt tgaaactgaa tagatgcgtc tagaagcgat gctacgctag tcacaatcac 53700cactttcata tttagaatat atatatgtaa aaatatagta gaatttcatt ttgttttttc 53760tatgctataa atgaattctc attttgcatc tgctcatact ccgttttata ttaataccaa 53820agaaggaaga tatctggttc taaaagccgt taaagtatgc gatgttagaa ctgtagaatg 53880cgaaggaagt aaagcttcct gcgtactcaa agtagataaa ccctcatcgc ccgcgtgtga 53940gagaagacct tcgtccccgt ccagatgcga gagaatgaat aaccctggaa aacaagttcc 54000gtttatgagg acggacatgc tacaaaatat gttcgcggct aatcgcgata atgtagcttc 54060tagacttttg tcctaaaata ctattatatc cttttcgata ttaataaatc cgtgtcgtcc 54120aggtttttta tctctttcag tatgtgaata gataggtatt ttatctctat tcatcatcga 54180atttaagaga tccgataaac attgtttgta ttctccagat gtcagcatct gatacaacaa 54240tatatgtgca cataaacctc tggcacttat ttcatgtacc ttccccttat cactaaggag 54300aatagtattt gagaaatatg tatacatgat attatcatga attagatata cagaatttgt 54360aacactctcg aaatcacacg atgtgtcggc gttaagatct aatatatcac tcgataacac 54420attttcatct agatacacta gacatttttt aaagctaaaa tagtctttag tagtgacagt 54480aactatgcga ttattttcat cgatgataca tttcatcggc atattattac gcttaccatc 54540aaagactata ccatgtgtat atctaacgta ttctagcatg gttgccatac gcgcattaaa 54600cttttcagga tctttggata gatcttccaa tctatctatt tgagaaaaca tttttatcat 54660gttcaatagt tgaaacgtcg gatccactat atagatatta tctataaaga ttttaggaac 54720tacgttcatg gtatcctggc gaatattaaa actatcaatg atatgattat cgttttcatc 54780ttttatcacc atatagtttc taagatatgg gattttactt aatataatat tatttcccgt 54840gataaatttt attagaaagg ccaaatctat aagaaaagtc ctagaattag tctgaagaat 54900atctatatcg ccgtatagta tatttggatt aattagatat agagaatatg atccgtaaca 54960tatacaactt ttattatggc gtctaagata ttcttccatc aacttattaa catttttgac 55020tagggaagat acattatgac gtcccattac ttttgccttg tctattactg cgacgttcat 55080agaatttagc atatctcttg ccaattcttc cattgatgtt acattataag aaattttaga 55140tgaaattaca tttggagctt taatagtaag aactcctaat atgtccgtgt atgtggtcac 55200taatacagat tgtagttcta taatcgtaaa taatttacct atattatatg tttgagtctg 55260tttagaaaag tagctaagta tacgatcttt tatttctgat gcagatgtat caacatcgga 55320aaaaaatctt tttttattct tttttactaa agatacaaat atgtctttgt taaaaacagt 55380tattttctga atatttctag cttgtaattt taacatatga tattcgttca cactaggtac 55440tctgcctaaa taggtttcta taatctttaa tgtaatatta ggaagagtat tctgatcagg 55500attcctattc attttgagga tttaaaactc tgattattgt ctaatatggt ctctacgcaa 55560actttttcac agagcgatag agtttttgat aactcgtttt tcttaagaaa tataaaacta 55620ctgtttccag agctcgctct atcttttatt ttatctaatt cgatacaaac tcctgatact 55680ggttcagaaa gtaattcatt aattttcagt cctttataga agatatttaa tatagataat 55740acaaaatctt cagtttttga tatcgatctg attgatccta gaactagata tattaataac 55800gtgctcatta ggcagtttat ggcagcttga taattagata tagtatattc cagttcatat 55860ttattagata ccgcattgcc cagattttga tattctatga attcctctga aaataaatcc 55920aaaataacta gacattctat tttttgtgga ttagtgtact ctcttccctc tatcatgttc 55980actactggtg tccacgatga taaatatcta gagggaatat aatatagtcc ataggatgcc 56040aatctagcaa tgtcgaataa ctgtaatttt attcttcgct cttcattatg aattgattct 56100tgaggtataa acctaacaca aattatatta ttagactttt cgtatgtaat gtctttcatg 56160ttataagttt ttaatcctgg aatagaatct attttaatga ggcttttaaa cgcagagttc 56220tccaacgagt caaagcataa tactctgttg tttttcttat atacgatgtt acgattttct 56280tctttgaatg gaataggttt ttgaattagt ttataattac aacataatag ataaggaagt 56340gtgcaaatag tacgcggaaa aaacataata gctcccctgt tttcatccat ggttttaagt 56400aaatgatcac tggcttcttt agtcaatgga tattcgaaca ttaaccgttt catcatcatt 56460ggacagaatc catatttctt aatgtaaaga gtgatcaaat cattgtgttt attgtaccat 56520cttgttgtaa atgtgtattc ggttatcgga tctgctcctt tttctattaa agtatcgata 56580tcgatctcgt ctaagaattc aactatatcg acatatttca tttgtataca cataaccatt 56640actaacgtag aatgtatagg aagagatgta acgggaacag ggtttgttga ttcgcaaact 56700attctaatac ataattcttc tgttaatacg tcttgcacgt aatctattat agatgccaag 56760atatctatat aattattttg taagatgatg ttaactatgt gatctatata agtagtgtaa 56820taattcatgt attttgatat atgttccaac tctgtctttg tgatgtctag tttcgtaata 56880tctatagcat cctcaaaaaa tatattcgca tatattccca agtcttcagt tctatcttct 56940aaaaaatctt caacgtatgg aatataataa tctattttac ctcttctgat atcattaatg 57000atatagtttt tgacactatc ttctgtcaat tgattcttat tcactatatc taagaaacgg 57060atagcgtccc taggacgaac tactgccatt aatatctcta ttatagcttc tggacataat 57120tcatctatta taccagaatt aatgggaact attccgtatc tatctaacat agttttaaga 57180aagtcagaat ctaagacttg atgttcatat attggttcat acatgaaatg atctctattg 57240atgatagtga ctatttcatt ctctgaaaat tggtaactca ttctatatat gctttccttg 57300ttgatgaagg atagaatata ctcaatagaa tttgtaccaa caaactgttc tcttatgaat 57360cgtatatcat catctgaaat aatcatgtaa ggcatacatt taacaattag agacttgtct 57420cctgttatca atatactatt cttgtgataa tttatgtgtg aggcaaattt gtccacgttc 57480tttaattttg ttatagtaga tatcaaatcc aatggagcta cagttcttgg cttaaacaga 57540tatagttttt ctggaacaaa ttctacaaca ttattataaa ggactttggg tagataagtg 57600ggatgaaatc ctattttaat taatgcgata gccttgtcct cgtgcagata tccaaacgct 57660tttgtgatag tatggcattc attgtctaga aacgctctac gaatatctgt gacagatatc 57720atctttagag aatatactag tcgcgttaat agtactacaa tttgtatttt ttaatctatc 57780tcaataaaaa aattaatatg tatgattcaa tgtataacta aactactaac tgttattgat 57840aactagaatc agaatctaat gatgacgtaa ccaagaagtt tatctactgc caatttagct 57900gcattatttt tagcatctcg tttagatttt ccatcggcct tatcgaatac tcttccgtcg 57960atatctacac aggcataaaa tgtaggagag ttactaggcc caactgattc aatacgaaaa 58020gaccaatctc tcttagttat ttggcagtac tcattaataa cggtgacagg gttagcatct 58080ttccaatcaa taattttttt agccggaata acatcatcaa aagacttatg atcctctctc 58140attgattttt cgcgggatac atcatctatt atggcgtcag ccataacatc agcatccggc 58200ttatccgcct ccgttgtcat aaaccaacga ggaggaatat cgtcggagct gtacaccata 58260gcactacgtt gaagatcgta cagagcttta ttaacttctc gcttctccat attaagttgt 58320ctagttagtt gtgcagcagt agctccttcg attccaatgg ttttaatagc ctcacacaca 58380atctctgcgt cagaacgctc gtcaatatag atcttagaca tttttagaga gaactaacac 58440aaccagcaat aaaactgaac ctactttatc atttttttat tcatcatcct ctggtggttc 58500gtcgttccta tcgaatgtgg atctgattaa cccgtcatct ataggtgatg ctggttctgg 58560agattctgga ggagatggat tattatctgg aagaatctct gttatttcct tgttttcatg 58620tatcgattgc gttgtaacat taagattgcg aaatgctcta aatttgggag gcttaaagtg 58680ttgtttgcaa tctctacacg cgtgtctaac tagtggaggt tcgtcagctg ctctagtttg 58740aatcatcatc ggtgtagtat tcctactttt acagttagga cacggtgtat tgtatttctc 58800gtcgagaacg ttaaaataat cgttgtaact cacatccttt attttatcta tattgtattc 58860tactcctttc ttaatgcatt ttataccgaa taagagatag cgaaggaatt ctttttcggt 58920gccgctagta cccttaatca tatcacatag tgttttatat tccaaatttg tggcaataga 58980cggtttattt ctatacgata gtttgtttct ggaatccttt gagtattcta taccaatatt 59040attctttgat tcgaatttag tttcttcgat attagatttt gtattaccta tattcttgat 59100gtagtacttt gatgattttt ccatggccca ttctattaag tcttccaagt tggcatcatc 59160cacatattgt gatagtaatt ctcggatatc agtagcggct accgccattg atgtttgttc 59220attggatgag taactactaa tgtatacatt ttccatttat aacacttatg tattaacttt 59280gttcatttat attttttcat tattatgttg atattaacaa aagtgaatat atatatgtta 59340ataattgtat tgtggttata cggctacaat tttataatga gtgaaagtca gtgtccgatg 59400atcaatgacg atagctttac tctgaaaaga aagtatcaaa tcgatagtgc ggagtcaaca 59460ataaaaatgg ataagaagag gataaagttt cagaatagag ccaaaatggt aaaagaaata 59520aatcagacaa taagagcagc acaaactcat tacgagacat tgaaactagg atacataaaa 59580tttaagagaa tgattatgac tactactcta gaagatatag caccatctat tccaaataat 59640cagaaaactt ataaactatt ctcggacatt tcagccatcg gcaaagcatc acagaatccg 59700agtaagatgg tatatgctct gctgctttac atgtttccca atttgtttgg agatgatcat 59760agattcattc gttatagaat gcatccaatg agtaaaatca aacacaagat cttctctcct 59820ttcaaactta atcttattag aatattagtg gaagaaagat tctataataa tgaatgcaga 59880tctaataaat ggagaataat tggaacacaa gttgataaaa tgttgatagc tgaatctgat 59940aaatatacaa tagatgcaag gtataaccta aaacccatgt atagaatcaa gggagaatct 60000gaagaagata ccctctttat caaacagatg gtagaacaat gtgtgacatc ccaggaattg 60060gtggaaaaag tgttgaagat actgtttaga gatttgttca agagtggaga atacaaagcg 60120tacagatacg atgatgatgt agaaaatgga tttattggat tggatacact aaaattaaac 60180attgttcatg atatagttga accatgtatg cctgttcgta ggccagtggc taagatactg 60240tgtaaagaaa tggtaaataa atactttgag aatccgctac atattattgg taaaaatctt 60300caagagtgca ttgactttgt tagtgaatag gcatttcatc tttctccaat actaattcaa 60360attgttaaat taataatgga tagtataaat agttattagt tataagatag taaaaataat 60420tattagaata agagtgtagt atcatagata actctcttct ataaaaatgg attttattcg 60480tagaaagtat cttatataca cagtagaaaa taatatagat tttttaaagg atgatacatt 60540aagtaaagta aacaatttta ccctcaatca tgtactagct ctcaagtatc tagttagcaa 60600ttttcctcaa cacgttatta ctaaggatgt attagctaat accaattttt ttgttttcat 60660acatatggta cgatgttgta aagtgtacga agcggtttta cgacacgcat ttgatgcacc 60720cacgttgtac gttaaagcat tgactaagaa ttatttatcg tttagtaacg caatacaatc 60780gtacaaggaa accgtgcata aactaacaca agatgaaaaa tttttagagg ttgccgaata 60840catggacgaa ttaggagaac ttataggcgt aaattatgac ttagttctta atccattatt 60900tcacggaggg gaacccatca aagatatgga aatcattttt ttaaaactgt ttaagaaaac 60960agacttcaaa gttgttaaaa aattaagtgt tataagatta cttatttggg catacctaag 61020caagaaagat acaggcatag agtttgcgga taatgataga caagatatat atactctatt 61080tcaacaaact ggtagaatcg tccatagcaa tctaacagaa acgtttagag attatatctt 61140tcccggagat aagactagct attgggtgtg gttaaacgaa agtatagcta atgatgcgga 61200tatcgttctt aatagacccg ccattaccat gtatgataaa attcttagtt atatatactc 61260tgagataaaa caaggacgcg ttaataaaaa catgcttaag ttagtttata tctttgagcc 61320tgaaaaagat atcagagaac ttctgctaga aatcatatat gatattcctg gagatatcct 61380atctattatt gatgcaaaaa acgacgattg gaaaaaatat tttattagtt tttataaagc 61440taattttatt aacggtaata catttattag tgatagaacg tttaacgagg acttattcag 61500agttgttgtt caaatagatc ccgaatattt cgataatgaa cgaattatgt ctttattctc 61560tacgagtgct gcggacatta aacgatttga tgagttagat attaataaca gttatatatc 61620taatataatt tatgaggtga acgatatcac attagataca atggatgata tgaagaagtg 61680tcaaatcttt aacgaggata cgtcgtatta tgttaaggaa tacaatacat acctgttttt 61740gcacgagtcg gatcccatgg tcatagagaa cggaatacta aagaaactgt catctataaa 61800atccaagagt agacggctga acttgtttag caaaaacatt ttaaaatatt atttagacgg 61860acaattggct cgtctaggtc ttgtgttaga tgattataaa ggagacttgt tagttaaaat 61920gataaaccat cttaagtctg tggaggatgt atccgcattc gttcgatttt ctacagataa 61980aaaccctagt attcttccat cgctaatcaa aactatttta gctagttata atatttccat 62040catcgtctta tttcaaaggt ttttgagaga taatctatat catgtagaag aattcttgga 62100taaaagcatc catctaacca agacggataa gaaatatata cttcaattga taagacacgg 62160tagatcatag aacagaccaa atatattatt aataatttgt atatacatag atataattat 62220cacacatttt tgataaatgg gaactgctgc aacaattcag actcccacca aattaatgaa 62280taaagaaaat gcagaaatga ttttggaaaa aattgttgat catatagtta tgtatattag 62340tgacgaatca agtgattcag aaaataatcc tgaatatatt gattttcgta acagatacga 62400agactataga tctctcatta taaaaagtga tcacgagttt gtaaagctat gtaaaaatca 62460tgcggagaaa agttctccag aaacgcaaca aatgattatc aaacacatat acgaacaata 62520tcttattcca gtatctgaag tactattaaa acttataatg tccatgggtg acataattac 62580atataacgga tgtaaagaca atgaatggat gctagaacaa ctctctaccc taaactttaa 62640caatctccgc acatggaact catgtagcat aggcaatgta acgcgtctgt tttatacatt 62700ttttagttat ctgatgaaag ataaactaaa tatataagta taatcccatt ctaatacttt 62760aacctgatgt attagcatct tattagaata ttaacctaac taaaagacat aacataaaaa 62820ctcattacat agttgataaa aagcggtagg atataaatat tatggctgcc accgttccgc 62880gttttgacga cgtgtacaaa aatgcacaaa gaagaattct agatcaagaa acatttttta 62940gtagaggtct aagtagaccg ttaatgaaaa acacatatct atttgataat tacgcgtatg 63000gatggatacc agaaactgca atttggagta gtagatacgc aaacttagat gcaagtgact 63060attatcccat ttcgttggga ttacttaaaa agtttgagtt tctcatgtct ctatataaag 63120gtcctattcc agtatacgaa gaaaaagtaa atactgaatt catagccaat ggatcgttct 63180ctggtagata cgtatcatat cttcgaaagt tttctgctct tccaacaaac gagtttatta 63240gttttttgtt actgacctcc atccctatct ataatatctt gttctggttt aaaaatactc 63300agtttgatat tactaaacac acattattca gatacgttta tacagataat gccaaacacc 63360tggcgttggc taggtatatg catcaaacag gagactataa gcctttgttt agtcgtctca 63420aagagaatta tatatttacc ggtcccgttc caataagtat caaagatata gatcacccta 63480atcttagtag agcaagaagt ccatccgatt atgagacatt agctaatatt agtactatat 63540tgtactttac caagtatgat ccggtattaa tgtttttatt gttttacgta cctgggtatt 63600caattactac aaaaattact ccagccgtag aatatctaat ggataaactg aatctaacaa 63660agagcgacgt acaactgttg taaattattt tatgcttcgt aaaatgtagg ttttgaacca 63720aacattcttt caaagaatga gatgcataaa actttattat ccaatagatt gactatttcg 63780gacgtcaatc gtttaaagta aacttcgtaa aatattcttt gatcactgcc gagtttaaaa 63840cttctatcga taattgtttc atatgtttta atatttacaa gttttttggt ccatggtaca 63900ttagccggac aaatatatgc aaaataatat cgttctccaa gttctatagt ttctggatta 63960tttttattat attcagtaac caaatacata ttagggttat ctgcggattt ataatttgag 64020tgatgcattc gactcaacat aaataattct agaggagacg atctactatc aaattcggat 64080cgtaaatctg tttctaaaga acggagaata tctatacata cctgattaga attcatccgt 64140ccttcagaca acatctcaga cagtctggtc ttgtatgtct taatcatatt cttatgaaac 64200ttggaaacat ctcttctagt ttcactagta cctttattaa ttctctcagg tacagatttt 64260gaattcgacg atgccgagta tttcatcgtt gtatatttct tcttcgattg cataatcaga 64320ttcttatata ccgcctcaaa ctctatttta aaattattaa acaatactct attattaatc 64380agtcgttcta actctttcgc tatttctata gacttatcga catcttgact gtctatctct 64440gtaaacacgg agtcggtatc tccatacacg ctacgaaaac gaaatctgta atctataggc 64500aacgatgttt tcacaatcgg attaatatct ctatcgtcca tataaaatgg attacttaat 64560ggattggcaa accgtaacat accgttagat aactctgctc catttagtac cgattctaga 64620tacaagatca ttctacgtcc tatggatgtg caactcttag ccgaagcgta tgagtataga 64680gcactatttc taaatcccat cagaccatat actgagttgg ctactatctt gtacgtatat 64740tgcatggaat cataaatggc cttttcagtt gaactggtag cctgttttaa catcttttta 64800tatctggctc tctctgccaa aaatgttctt aatagtctag gaatggttcc ttctatcgat 64860ctatcgaaaa ttgctatttc agagatgagg ttcggtagtc taggttcaca atgaaccgta 64920atatatctag gaggtggata tttctgaagc aagagctgat tatttatttc ttcttccaat 64980ctattggtac taacaacgac accgactaat gtttccggag atagatttcc aaagatacac 65040acattaggat acagactgtt ataatcaaag attaatacat tattactaaa cattttttgt 65100tttggagcaa ataccttacc gccttcataa ggaaactttt gttttgtttc tgatctaact 65160aagatagttt tagtttccaa caatagcttt aacagtggac ccttgatgac tgtactcgct 65220ctatattcga ataccatgga ttgaggaagc acatatgttg acgcacccgc gtctgttttt 65280gtttctactc cataatactc ccacaaatac tgacacaaac aagcatcatg aatacagtat 65340ctagccatat ctaaagctat gtttagatta taatccttat acatctgagc taaatcaacg 65400tcatcctttc cgaaagataa tttatatgta tcattaggta aagtaggaca taatagtacg 65460actttaaatc cattttccca aatatcttta cgaattactt tacatataat atcctcatca 65520acagtcacat aattacctgt ggttaaaacc tttgcaaatg cagcggcttt gcctttcgcg 65580tctgtagtat cgtcaccgat gaacgtcatt tctctaactc ctctatttaa tactttaccc 65640atgcaactga acgcgttctt ggatatagaa tccaatttgt acgaatccaa tttttcaaat 65700ttttgaatga atgaatatag atcgaaaaat atagttccat tattgttatt aacgtgaaac 65760gtagtattgg ccatgccgcc tactccctta tgactagact gatttctctc ataaatacag 65820agatgtacag cttccttttt gtccggagat ctaaagataa tcttctctcc tgttaataac 65880tctagacgat tagtaatata tctcagatca aagttatgtc cgttaaaggt aacgacgtag 65940tcgaacgtta gttccaacaa ttgtttagct attcgtaaca aaactatttc agaacataga 66000actagttctc gttcgtaatc catttccatt agtgactgta tcctcaaaca tcctctatcg 66060acggcttctt gtatttcctg ttccgttaac atctcttcat taatgagcgt aaacaataat 66120cgtttaccac ttaaatcgat ataacagtaa cttgtatgcg agattgggtt aataaataca 66180gaaggaaact tcttatcgaa gtgacactct atatctagaa ataagtacga tcttgggata 66240tcgaatctag gtattttttt agcgaaacag ttacgtggat

cgtcacaatg ataacatcca 66300ttgttaatct ttgtcaaata ttgctcgtcc aacgagtaac atccgtctgg agatatcccg 66360ttagaaatat aaaaccaact aatattgaga aattcatcca tggtggcatt ttgtatgctg 66420cgtttctttg gctcttctat caaccacata tctgcgacgg agcattttct atctttaata 66480tctagattat aacttattgt ctcgtcaatg tctatagttc tcatctttcc caacggcctc 66540gcattaaatg gaggaggaga caatgactga tatatttcgt ccgtcactac gtaataaaag 66600taatgaggaa atcgtataaa tacggtctcg ccatttcgac atctggattt cagatataaa 66660aatctgtttt caccgtgact ttcaaaccaa ttaatgcacc gaacatccat ttatagaatt 66720tagaaatata ttttcattta aatgaatccc aaacattggg gaagagccgt atggaccatt 66780atttttatag tactttcgca agcgggttta gacggcaaca tagaagcgtg taaacgaaaa 66840ctatatacta tagttagcac tcttccatgt cctgcatgta gacggcacgc gactattgct 66900ataaaggaca ataatgtcat gtctagcgat gatctgaatt atatttatta ttttttcatc 66960agattattta acaatttggc atctgatccc aaatacgcga tcgatgtgac aaaggttaac 67020cctttataaa cttaacccat tataaaactt atgattagtc acaactgaaa taaccgcgtg 67080attatttttt ggtataattc tacacggcat ggtttctgtg actatgaatt caacccccgt 67140tacattagtg aaatctttaa caaacagcaa gggttcgtca aagacataaa actcattgtt 67200tacaatcgaa atagaccccc tatcacactt aaaataaaaa atatccttat cctttaccac 67260caaataaaat tctgattggt caatgtgaat gtattcactt aacagttcca caaatttatt 67320tattaactcc gaggcacata catcgtcggt attttttatg gcaaacttta ctcttccagc 67380atccgtttct aaaaaaatat taacgagttc catttatatc atccaatatt attgaaatga 67440cgttgatgga cagatgatac aaataagaag gtacggtacc tttgtccacc atctcctcca 67500attcatgctc tattttgtca ttaactttaa tgtatgaaaa cagtacgcca catgcttcca 67560tgacagtgtg taacactttg gatacaaaat gtttgacatt agtataattg tccaagactg 67620tcaatctata atagatagta gctataatat attctatgat ggtattgaag aagatgacaa 67680ccttggcata ttgatcattt aacacagaca tggtatcaac agatagcttg aatgaaagag 67740aatcagtaat tggaataagc gtcttctcga tagagtgtcc gtataccaac atgtctgata 67800ttttgatgta ttccattaaa ttatttagtt ttttcttttt attctcgtta aacagcattt 67860ctgtcaacgg accccaacat cgttgaccga ttaagttttg attgattttt ccgtgtaagg 67920cgtatctagt cagatcgtat agcctatcca ataatccatc gtctgtgtgt agatcacatc 67980gtacactttt taattctcta tagaagagcg acagacatct ggagcaatta cagacagcaa 68040tttctttatt ctctacagat gtaagatact tgaagacatt cctatgatga tgcagaattt 68100tggataacac ggtattgatg gtatctgtta ccataattcc tttgatggct gatagtgtca 68160gagcacaaga tttccaatct ttgacaattt ttagcaccat tatctttgtt ttgatatcta 68220tatcagacag catggtgcgt ctgacaacac agggattaag acggaaagat gaaatgattc 68280tctcaacatc ttcaatggat accttgctat tttttctggc attatctata tgtgcgagaa 68340tatcctctag cctgcaggtc aattcggtag ttgcgatata cataaactga tcactaattc 68400caaacccacc cactttttat agtaagtttt tcacccataa ataataaata caataattaa 68460tttctcgtaa aagtagaaaa tatattctaa tttattgcac ggtaaggaag tagtcgaaac 68520gaattcgccc ttgcttgcaa gccaccatgg cctcctccga ggacgtcatc aaggagttca 68580tgcgcttcaa ggtgcgcatg gagggctccg tgaacggcca cgagttcgag atcgagggcg 68640agggcgaggg ccgcccctac gagggcaccc agaccgccaa gctgaaggtg accaagggcg 68700gccccctgcc cttcgcctgg gacatcctgt ccccccagtt ccagtacggc tccaaggtgt 68760acgtgaagca ccccgccgac atccccgact acaagaagct gtccttcccc gagggcttca 68820agtgggagcg cgtgatgaac ttcgaggacg gcggcgtggt gaccgtgacc caggactcct 68880ccctgcagga cggctccttc atctacaagg tgaagttcat cggcgtgaac ttcccctccg 68940acggccccgt aatgcagaag aagactatgg gctgggaggc ctccaccgag cgcctgtacc 69000cccgcgacgg cgtgctgaag ggcgagatcc acaaggccct gaagctgaag gacggcggcc 69060actacctggt ggagttcaag tccatctaca tggccaagaa gcccgtgcag ctgcccggct 69120actactacgt ggactccaag ctggacatca cctcccacaa cgaggactac accatcgtgg 69180agcagtacga gcgcgccgag ggccgccacc acctgttcct gtaggcgcgc ctataagggc 69240gaattcgcgg cctcgacgct agagaatcag tatccttttt gatgatagtg gatctcaatg 69300acatgggacg tctaaacctt cttattctat caccagattg catggtgatt tgtcttcttt 69360cttttatcat aatgtaatct ctaaattcat cggcaaattg tctatatcta aaatcataat 69420atgagatgtt tacctctaca aatatctgtt cgtccaatgt tagagtattt acatcagttt 69480tgtattccaa attaaacatg gcaacggatt taattttata ttcctctatt aagtcctcgt 69540cgataataac agaatgtaga taatcattta atccatcgta catggttgga agatgcttgt 69600tgacaaaatc tttaattgtc ttgatgaagg tgggactata tctaacatct tgattaataa 69660aatttataac attgtccata ggatactttg taactagttt tatacacatc tcttcatcgg 69720taagtttaga cagaatatcg tgaacaggtg gtatattata ttcatcagat atacgaagaa 69780caatgtccaa atctatattg tttaatatat tatatagatg tagcgtagct cctacaggaa 69840tatctttaac taagtcaatg atttcatcaa ccgttagatc tattttaaag ttaatcatat 69900aggcattgat ttttaaaagg tatgtagcct tgactacatt ctcattaatt aaccattcca 69960agtcactgtg tgtaagaaga ttatattcta tcataagctt gactacattt ggtcccgata 70020ccattaaaga attcttatga tataaggaaa cagcttttag gtactcatct actctacaag 70080aattttggag agccttaacg atatcagtga cgtttattat ttcaggagga aaaaacctaa 70140cattgagaat gtcggagtta atagcttcca gatacagtga ttttggcaat agtccgtgta 70200atccataatc cagtaacacg agctggtgct tgctagacac cttttcaatg tttaattttt 70260ttgaaataag ctttgataaa gccttcctcg caaattccgg atacatgaac atgtcggcga 70320catgattaag tattgttttt tcattatttt tatattttct caacaagttc tcaatacccc 70380aatagatgat agaatatcac ccaatgcgtc catgttgtct atttccaaca ggtcgctata 70440tccaccaata gaagtttttc caaaaaagat tctaggaaca gttctaccac cagtaatttg 70500ttcaaaataa tcacgcaatt cattttcggg tttaaattct ttaatatcga caatttcata 70560cgctcctctt ttgaaactaa acttatttag aatatccagt gcatttctac aaaaaggaca 70620tgtatacttg acaaaaattg tcactttgtt attggccaac ctttgttgta caaattcctc 70680ggccatttta atatttaagt gatataaaac tatctcgact tatttaactc tttagtcgag 70740atatatggac gcagatagct atatgatagc caactacaga aggcaaacgc tataaaaaac 70800ataattacaa cgagcatatt tataaatatt tttattcagc attacttgat atagtaatat 70860taggcacagt caaacattca accactctcg atacattaac tctctcattt tctttaacaa 70920attctgcaat atcttcgtaa aaagattctt gaaacttttt agaatatcta tcgactctag 70980atgaaatagc gttcgtcaac atactatgtt ttgtatacat aaaggcgcct attttaacag 71040tttctagtga caaaatgcta gcgatcctag gatcctttag aatcacatag attgacgatt 71100cgtctctctt agtaactcta gtaaaataat catacaatct agtacgcgaa ataatattat 71160ccttgacttg aggagatcta aacaatctag ttttgagaac atcgataagt tcatcgggaa 71220tgacatacat actatcttta atagaactct tttcatccag ttgaatggat tcgtccttaa 71280ccaactgatt aatgagatct tctattttat cattttccag atgatatgta tgtccattaa 71340agttaaattg tgtagcgctt ctttttagtc tagcagccaa tactttaaca tcactaatat 71400cgatatacaa aggagatgat ttatctatgg tattaagaat tcgtttttcg acatctgtca 71460aaaccaattc ctttttgcct gtatcatcca gttttccatc ctttgtaaag aaattatttt 71520ctactagact attaataaga ctgataagga ttcctccata attgcacaat ccaaactttt 71580taacaaaact agactttaca agatctacag gaatgcgtac ttcaggtttt ttagcttgtg 71640attttttctt ttgcggacat tttctagtaa ccaactcatc taccatttca ttgattttag 71700cagtgaaata agctttcaat gcacgggcac tgatactatt gaaaacgagt tgatcttcaa 71760attccgccat ttaagttcac caaacaactt ttaaatacaa atatatcaat agtagtagaa 71820taagaactat aaaaaaaata ataattaacc aataccaacc ccaacaaccg gtattattag 71880ttgatgtggt agttttctca tcacttagaa cagatttaac aatttctata aagtctgtca 71940aatcatcttc cggagacccc ataaatacac caaatatagc ggcgtacaac ttatccattt 72000atacattgaa tattggcttt tctttatcgc tatcttcatc atattcatca tcaatatcaa 72060caagtcccag attacgagcc agatcttctt ctacattttc agtcattgat acacgttcac 72120tatctccaga gagtccgata acgttagcca ccacttctct atcaatgatt agtttcttga 72180gcgcgaatgt aatttttgtt tccgttccgg atctatagaa gacgataggt gtgataattg 72240ccttggccaa ttgtctttct cttttactga gtgattctag ttcaccttct atagatctga 72300gaatggatga ttctccagtc gaaacatatt ctaccatgga tccgtttaat ttgttgatga 72360agatggattc atccttaaat gttttctctg taatagtttc caccgaaaga ctatgcaaag 72420aatttggaat gcgttccttg tgcttaatgt ttccatagac ggcttctaga agttgataca 72480acataggact agccgcggta acttttattt ttagaaagta tccatcgctt ctatcttgtt 72540tagatttatt tttataaagt ttagtctctc cttccaacat aataaaagtg gaagtcattt 72600gactagataa actatcagta agttttatag agatagacga acaattagcg tattgagaag 72660catttagtgt aacgtattcg atacattttg cattagattt actaatcgat tttgcatact 72720ctataacacc cgcacaagtc tgtagagaat cgctagatgc agtaggtctt ggtgaagttt 72780caactctctt cttgattacc ttactcatga ttaaacctaa ataattgtac tttgtaatat 72840aatgatatat attttcactt tatctcattt gagaataaaa atgtttttgt ttaaccactg 72900catgatgtac agatttcgga atcgcaaacc accagtggtt ttattttatc cttgtccaat 72960gtgaattgaa tgggagcgga tgcgggtttc gtacgtagat agtacattcc cgtttttaga 73020ccgagactcc atccgtaaaa atgcatactc gttagtttgg aataactcgg atctgctata 73080tggatattca tagattgact ttgatcgatg aaggctcccc tgtctgcagc catttttatg 73140atcgtctttt gtggaatttc ccaaatagtt ttataaactc gcttaatatc ttctggaagg 73200tttgtattct gaatggatcc accatctgcc ataatcctat tcttgatctc atcattccat 73260aattttctct cggttaaaac tctaaggaga tgcggattaa ctacttgaaa ttctccagac 73320aatactctcc gagtgtaaat attactggta tacggttcca ccgactcatt atttcccaaa 73380atttgagcag ttgatgcagt cggcataggt gccaccaata aactatttct aagaccgtat 73440gttctgattt tatcttttag aggttcccaa ttccaaagat ccgacggtac aacattccaa 73500agatcatatt gtagaatacc gttactggcg tacgatccta catatgtatc gtatggtcct 73560tccttctcag ctagttcaca actcgcctct aatgcaccgt aataaatggt ttcgaagatc 73620ttcttattta gatcttgtgc ttccaggcta tcaaatggat aatttaagag aataaacgcg 73680tccgctaatc cttgaacacc aataccgata ggtctatgtc tcttattaga gatttcagct 73740tctggaatag gataataatt aatatctata attttattga gatttctgac aattactttg 73800accacatcct tcagtttgag aaaatcaaat cgcccatcta ttacaaacat gttcaaggca 73860acagatgcca gattacaaac ggctacctca ttagcatccg catattgtat tatctcagtg 73920caaagattac tacacttgat agttcctaaa ttttgttgat tactcttttt gttacacgca 73980tccttataaa gaatgaatgg agtaccagtt tcaatctgag attctataat cgctttccag 74040acgactcgag cctttattat agatttgtat ctcctttctc tttcgtatag tgtatacaat 74100cgttcgaact cgtctcccca aacattgtcc aatccaggac attcatccgg acacatcaac 74160gaccactctc cgtcatcctt cactcgtttc ataaagagat caggaatcca aagagctata 74220aatagatctc tggttctatg ttcctcgttt cctgtattct ttttaagatc gaggaacgcc 74280ataatatcag aatgccacgg ttccaagtat atggccataa ctccaggccg tttgtttcct 74340ccctgatcta tgtatctagc ggtgttatta taaactctca acattggaat aataccgttt 74400gatataccat tggtaccgga gatatagctt ccactggcac gaatattact aattgataga 74460cctattcccc ctgccatttt agagattaat gcgcatcgtt ttaacgtgtc atagataccc 74520tctatgctat catcgatcat gttaagtaga aaacagctag acatttggtg acgactagtt 74580cccgcattaa ataaggtagg agaagcgtgc gtaaaccatt tttcagaaag tagattgtac 74640gtctcaatag ctgagtctat atcccattga tgaattccta ctgcgacacg cattaacatg 74700tgctgaggtc tttcaacgat cttgttgttt attttcaaca agtaggattt ttccaaagtt 74760ttaaaaccaa aatagttgta tgaaaagtct cgttcgtaaa taataaccga gttgagttta 74820tccttatatt tgttaactat atccatggtg atacttgaaa taatcggaga atgtttccca 74880tttttaggat taacatagtt gaataaatcc tccatcactt cactaaatag tttttttgtt 74940tccttgtgta gatttgatac ggctattctg gcggctaaaa tggcataatc cggatgttgt 75000gtagtacaag tggctgctat ttcggctgcc agagtgtcca attctaccgt tgttactcca 75060ttatatattc cttgaataac cttcatagct attttaatag gatctatatg atccgtgttt 75120aagccataac ataattttct aatacgagac gtgattttat caaacatgac attttccttg 75180tatccatttc gtttaatgac aaacattttt gttggtgtaa taaaaaaatt atttaacttt 75240tcattaatag ggatttgacg tacgtagcgt acaaaatgat cgttcctggt atatagataa 75300agagtcctat atatttgaaa atcgttacgg ctcgattaaa ctttaatgat tgcatagtga 75360atatatcatt aggatttaac tccttgacta tcatggcggc gccagaaatt accatcaaaa 75420gcattaatac agttatgccg atcgcagtta gaacggttat agcatccacc atttatatct 75480aaaaattaga tcaaagaata tgtgacaaag tcctagttgt atactgagaa ttgacgaaac 75540aatgtttctt acatattttt ttcttattag taactgactt aatagtagga actggaaagc 75600tagacttgat tattctataa gtatagatac ccttccaaat aatattctct ttgataaaag 75660ttccagaaaa tgtagaattt tttaaaaagt tatcttttgc tattaccaag attgtgttta 75720gacgcttatt attaatatga gtgatgaaat ccacaccgcc tctagatatc gcctttattt 75780ccacattaga tggtaaatcc aatagtgaaa ctatcttttt aggaatgtat ggactcgcgt 75840ttagaggagt gaacgtcttg ggcgtcggaa aggatgattc gtcaaacgaa taaacaattt 75900cacaaatgga tgttaatgta ttagtaggaa atttcttgac gctattggaa ttgaagattc 75960taatggatga tgttctacct atttcatccg ataacatgtt aatttccgac accaacggtt 76020ttaatatttc gatgatatac ggtagtctct ctttcggact tatatagctt attccacaat 76080acgagtcatt atatactcca aaaaacaaaa taactagtat aaaatctgta tcgaatggga 76140aaaacgaaat tatcgacata ggtatagaat ccggaacatt gaacgtatta atacttaatt 76200ctttttctgt ggtaagtacc gataggttat tgacattgta tggttttaaa tattctataa 76260cttgagactt gatagatatt agtgatgaat tgaaaattat ttttatcacc acgtgtgttt 76320caggatcatc gtcgacgcct gtcaaccaac cgaatggagt aaaataaata tcattaatat 76380atgctctaga tattagtatt tttatcaatc ctttgattat catcttctcg taggcgaatg 76440attccatgat caagagtgat ttgagaacat cctccggagt attaatgggc ttagtaaaca 76500gtccatcgtt gcaataataa aagttatcca agttaaagga tattatgcat tcgtttaaag 76560atatcacctc atctgacgga gacaattttt tggtaggttt tagagacttt gaagctactt 76620gtttaacaaa gttattcatc gtcgtctact attctattta attttgtagt taatttatca 76680catatcacat taattgactt tttggtccat ttttccatac gtttatattc ttttaatcct 76740gcgttatccg tttccgttat attcagggat agatcttgca agttaaatag aatgctctta 76800aataatgtca ttttcttatc cgctaaaaat ttaaagaatg tataaacctt tttcagagat 76860ttgaaactct taggtggtgt cctagtacac aatatcataa acaaactaat aaacattcca 76920cattcagatt ccaacagctg attaacttcc acattaatac agcctatttt cgctccaaat 76980gtacattcga aaaatctgaa taaaacatcg atgtcacaat ttgtattatc caatacagaa 77040tgtttgtgat tcgtgttaaa accatcggag aaggaataga aataaaaatt attatagtgg 77100tggaattcag ttggaatatt gcctccggag tcataaaagg atactaaaca ttgtttttta 77160tcataaatta cacatttcca atgagacaaa taacaaaatc caaacattac aaatctagag 77220gtagaacttt taattttgtc tttaagtata tacgataaga tatgtttatt cataaacgcg 77280tcaaattttt catgaatcgc taaggagttt aagaatctca tgtcaaattg tcctatataa 77340tccacttcgg atccataagc aaactgagag actaagttct taatacttcg attgctcatc 77400caggctcctc tctcaggctc tattttcatc ttgacgacct ttggattttc accagtatgt 77460attcctttac gtgataaatc atcgattttc aaatccattt gtgagaagtc tatcgcctta 77520gatacttttt cccgtagtcg aggtttaaaa aaatacgcta acggtatact agtaggtaac 77580tcaaagacat catatataga atggtaacgc gtctttaact cgtcggttaa ctctttcttt 77640tgatcgagtt cgtcgctact attgggtctg ctcaggtgcc ccgactctac tagttccaac 77700atcataccga taggaataca agacactttg ccggcggttg tagatttatc atatttttcc 77760actacatatc cgttacaatt tgttaaaaat ttagatacat ctatattgct acataatcca 77820gctagtgaat atatatgaca taataaattg gtaaatccta gttctggtat tttactaatt 77880actaaatctg tatatctttc catttatcat ggaaaagaat ttaccagata tcttcttttt 77940tccaaactgc gttaatgtat tctcttacaa atattcacaa gatgaattca gtaatatgag 78000taaaacggaa cgtgatagtt tctcattggc cgtgtttcca gttataaaac atagatggca 78060taacgcacac gttgtaaaac ataaaggaat atacaaagtt agtacagaag cacgtggaaa 78120aaaagtatct cctccatcac taggaaaacc cgcacacata aacctaaccg cgaagcaata 78180tatatacagt gaacacacaa taagctttga atgttatagt tttctaaaat gtataacaaa 78240tacagaaatc aattcgttcg atgagtatat attaagagga ctattagaag ctggtaatag 78300tttacagata ttttccaatt ccgtaggtaa acgaacagat actataggtg tactagggaa 78360taagtatcca tttagcaaaa ttccattggc ctcattaact cctaaagcac aacgagagat 78420attttcagcg tggatttctc atagacctgt agttttaact ggaggaactg gagtgggtaa 78480gacgtcacag gtacccaagt tattgctttg gtttaattat ttatttggtg gattctctac 78540tctagataaa atcactgact ttcacgaaag accagtcatt ctatctcttc ctaggatagc 78600tttagttaga ttgcatagca ataccatttt aaaatcattg ggatttaagg tactagatgg 78660atctcctatt tctttacggt acggatctat accggaagaa ttaataaaca aacaaccaaa 78720aaaatatgga attgtatttt ctacccataa gttatctcta acaaaactat ttagttatgg 78780cactcttatt atagacgaag ttcatgagca tgatcaaata ggagatatta ttatagcagt 78840agcgagaaag catcatacga aaatagattc tatgttttta atgactgcca cattagagga 78900tgaccgagaa cggctaaaag tatttttacc taatcccgca tttatacata ttcctggaaa 78960tacactgttt aaaattagcg aggtatttat tcataataag ataaatccat cttccagaat 79020ggcatacata gaagaagaaa agagaaattt agttactgct atacagatgt atactcctcc 79080tgatggatca tccggtatag tctttgtggc atccgttgca cagtgtcacg aatataaatc 79140atatttagaa aaaagattac cgtatgatat gtatattatt catggtaagg tcttagatat 79200agacgaaata ttagaaaaag tgtattcatc acctaatgta tcgataatta tttctactcc 79260ttatttggaa tccagcgtta ctatacgcaa tgttacacac atttatgata tgggtagagt 79320ttttgtcccc gctccttttg gaggatcgca acaatttatt tctaaatcta tgagagatca 79380acgaaaagga agagtaggaa gagttaatcc tggtacatac gtctatttct atgatctgtc 79440ttatatgaag tctatacagc gaatagattc agaatttcta cataattata tattgtacgc 79500taataagttt aatctaacac tccccgaaga tttgtttata atccctacaa atttggatat 79560tctatggcgt acaaaggaat atatagactc gttcgatatt agtacagaaa catggaataa 79620attattatcc aattattata tgaagatgat agagtatgct aaactttatg tactaagtcc 79680tattctcgct gaggagttgg ataactttga gaggacggga gaattaacta gtattgtacg 79740agaagccatt ttatctctaa atttacgaat taagatttta aattttaaac ataaagatga 79800tgatacgtat atacactttt gtaaaatatt attcggtgtc tataacggaa caaacgctac 79860tatatattat catagacctc taacgggata tatgaatatg atttcagata ctatatttgt 79920tcctgtagat aataactaaa aatcaaactc taatgaccac atcttttttt agagatgaaa 79980aattttccac atctcctttt gtagacacga ctaaacattt tgcagaaaaa agtttattag 80040tgtttagata atcgtatact tcatcagtgt agatagtaaa tgtgaacaga taaaaggtat 80100tcttgctcaa tagattggta aattccatag aatatattaa tcctttcttc ttgagatccc 80160acatcatttc aaccagagac gttttatcca atgatttacc tcgtactata ccacatacaa 80220aactagattt tgcagtgacg tcgtacctgg tattcctacc aaacaaaatt ttacttttag 80280ttcttttaga aaattctaag gtagaatctc tatttgccaa tatgtcatct atggaattac 80340cactagcaaa aaatgataga aatatatatt gatacatcgc agctggtttt gatctactat 80400actttaaaaa cgaatcagat tccataattg cctgtatatc atcagctgaa aaactatgtt 80460ttacacgtat tccttcggca tttcttttta atgatatatc ttgtttagac aatgataaag 80520ttatcatgtc catgagagac gcgtctccgt atcgtataaa tatttcatta gatgttagac 80580gcttcattag gggtatactt ctataaggtt tcttaatcag tccatcattg gttgcgtcaa 80640gaactactat cggatgttgt tgggtatctc tagtgttaca catggcctta ctaaagtttg 80700ggtaaataac tatgatatct ctattaatta tagatgcata tatttcattt gtcaaggata 80760ttagtatcga cttgctatcg tcattaatac gtgtaatgta atcatataaa tcatgcgata 80820gccaaggaaa atttaaatag atgttcatca tataatcgtc gctataattc atattaatac 80880gttgacattg actaatttgt aatatagcct cgccacgaag aaagctctcg tattcagttt 80940catcgataaa ggataccgtt aaatataact ggttgccgat agtctcatag tctattaagt 81000ggtaagtttc gtacaaatac agaatcccta aaatattatc taatgttgga ttaatcttta 81060ccataactgt ataaaatgga gacggagtca taactatttt accgtttgta cttactggaa 81120tagatgaagg aataatctcc ggacatgctg gtaaagaccc aaatgtctgt ttgaagaaat 81180ccaatgttcc aggtcctaat ctcttaacaa aaattacgat attcgatccc gatatccttt 81240gcattctatt taccagcata tcacgaacta tattaagatt atctatcatg tctattctcc 81300caccgttata taaatcgcct ccgctaagaa acgttagtat

atccatacaa tggaatactt 81360catttctaaa atagtattcg ttttctaatt ctttaatgtg aaatcgtata ctagaaaggg 81420aaaaattatc tttgagtttt ccgttagaaa agaaccacga aactaatgtt ctgattgcgt 81480ccgattccgt tgctgaatta atggatttac accaaaaact catataactt ctagatgtag 81540aagcattcgc taaaaaatta gtagaatcaa aggatataag tagatgttcc aacaagtgag 81600caattcccaa gatttcatct atatcattct cgaatccgaa attagaaatt cccaagtaga 81660tatccttttt catccgatcg ttgatgaaaa tacgaacttt attcggtaag acaatcattt 81720actaaggagt aaaataggaa gtaatgttcg tatgtcgtta tcatcgtata aattaaaggt 81780gtgtttttta ccattaagtg acattataat tttaccaata ttggaattat aatataggtg 81840tatttgcgca ctcgcgacgg ttgatgcatc ggtaaatata gctgtatcta atgttctagt 81900cggtatttca tcatttcgct gtctaataat agcgttttct ctatctgttt ccattacagc 81960tgcctgaagt ttattggtcg gataatatgt aaaataataa gaaatacata cgaataacaa 82020aaataaaata agatataata aagatgccat ttagagatct aattttgttc aacttgtcca 82080aattcctact tacagaagat gaggaatcgt tggagatagt gtcttcctta tgtagaggat 82140ttgaaatatc ttataatgac ttgataactt actttccaga taggaaatac cataaatata 82200tttataaagt atttgaacat gtagatttat cggaggaatt aagtatggaa ttccatgata 82260caactctgag agatttagtc tatcttagat tgtacaagta ttccaagtgt atacggccgt 82320gttataaatt aggagataat ctaaaaggca tagttgttat aaaggacagg aatatttata 82380ttagggaagc aaatgatgac ttgatagaat atctcctcaa ggaatacact cctcagattt 82440atacatattc taatgagcgc gtccccataa ctggttcaaa attaattctt tgtggatttt 82500ctcaagttac atttatggcg tatacaacgt cgcatataac aacaaataaa aaggtagatg 82560ttctcgtttc caaaaaatgt atagatgaac tagtcgatcc aataaattat caaatacttc 82620aaaatttatt tgataaagga agcggaacaa taaacaaaat actcaggaag atattttatt 82680cggtaacagg tggccaaact ccataggtag ctttttctat ttcggatttt agaatttcca 82740aattcaccag cgatttatcg gttttggtga aatccaagga tttattaatg tccacaaatg 82800ccatttgttt tgtctgtgga ttgtatttga aaatggaaac gatgtagtta gatagatgcg 82860ctgcgaagtt tcctattagg gttccgcgct tcacgtcacc cagcatactt gaatcaccat 82920cctttaaaaa aatgataaga tatcaacatg gagtatatca tactcggatt ttaattcttc 82980tactgactca ctgacatttt cacaaatact acaatacggt ttaccgaaaa taatcagtac 83040gttcttcatt tatgggtatc aaaaacttaa aatcgttact gctggaaaat aaatcactga 83100cgatattaga tgataattta tacaaagtat acaatggaat atttgtggat acaatgagta 83160tttatatagc cgtcgccaat tgtgtcagaa acttagaaga gttaactacg gtattcataa 83220aatacgtaaa cggatgggta aaaaagggag ggcatgtaac cctttttatc gatagaggaa 83280gtataaaaat taaacaagac gttagagaca agagacgtaa atattctaaa ttaaccaagg 83340acagaaaaat gctagaatta gaaaagtgta catccgaaat acaaaatgtt accggattta 83400tggaagaaga aataaaggca gaaatgcaat taaaaatcga taaactcaca tttcaaatat 83460atttatctga ttctgataac ataaaaatat cattgaatga gatactaaca catttcaaca 83520ataatgagaa tgttacatta ttttattgtg atgaacgaga cgcagaattc gttatgtgtc 83580tcgaggctaa aacacatttc tctaccacag gagaatggcc gttgataata agtaccgatc 83640aggatactat gctatttgca tctgctgata atcatcctaa gatgataaaa aacttaactc 83700aactgtttaa atttgttccc tcggcagagg ataactattt agcaaaatta acggcgttag 83760tgaatggatg tgatttcttt cctggactct atggggcatc tataacaccc accaacttaa 83820acaaaataca attgtttagt gattttacaa tcgataatat agtcactagt ttggcaatta 83880aaaattatta tagaaagact aactctaccg tagacgtgcg taatattgtt acgtttataa 83940acgattacgc taatttagac gatgtctact cgtatattcc tccttgtcaa tgcactgttc 84000aagaatttat attttccgca ttagatgaaa aatggaatga atttaaatca tcttatttag 84060agaccgttcc gttaccctgt caattaatgt acgcgttaga accacgtaag gagattgatg 84120tttcagaagt taaaacttta tcatcttata tagatttcga aaatactaaa tcagatatcg 84180atgttataaa atctatatcc tcgatcttcg gatattctaa cgaaaactgt aacacgatag 84240tattcggcat ctataaggat aatttactac tgagtataaa tagttcattt tactttaacg 84300atagtctgtt aataaccaat actaaaagtg ataatataat aaatataggt tactagatta 84360aaaatggtgt tccaactcgt gtgctctacg tgcggcaaag atatttctca cgaacgatat 84420aaattgatta tacgaaaaaa atcattaaag gatgtactcg tcagtgtaaa gaacgaatgt 84480tgtaggttaa aattatctac acaaatagaa cctcaacgta acttaacagt gcaacctcta 84540ttggatataa actaatatgg atccggttaa ttttatcaag acatatgcgc ctagaggttc 84600tattattttt attaattata ccatgtcatt aacaagtcat ttgaatccat cgatagaaaa 84660acatgtgggt atttattatg gtacgttatt atcggaacac ttggtagttg aatctaccta 84720tagaaaagga gttcgaatag tcccattgga tagttttttt gaaggatatc ttagtgcaaa 84780agtatacatg ttagagaata ttcaagttat gaaaatagca gctgatacgt cattaacttt 84840attgggtatt ccgtatggat ttggtcatga tagaatgtat tgttttaaat tggtagctga 84900ctgttataaa aatgccggta ttgatacatc gtctaaacga atattaggta aagatatttt 84960tctgagccaa aacttcacag acgataatag atggataaag atatatgatt ctaataattt 85020aacattttgg caaattgatt accttaaagg gtgagttaat atgcataact actcctccgt 85080tgttttttcc ctcgttcttt ttcttaacgt tgtttgccat cactctcata atgtaaagat 85140attctaaaat ggtaaacttt tgcatatcgg acgcagaaat tggtataaat gttgtaattg 85200tattatttcc cgtcaatgga ctagtcacag ctccatcagt tttatatcct ttagagtatt 85260tctcactcgt gtctagcatt ctagagcatt ccatgatctg tttatcgttg atattggccg 85320gaaagataga ttttttattt tttattatat tactattggc aattgtagat ataacttctg 85380gtaaatattt ttctaccttt tcaatctctt ctattttcaa gccggctata tattctgcta 85440tattgttgct agtatcaata ccttttctgg ctaagaagtc atatgtggta ttcactatat 85500cagttttaac tggtagttcc attagccttt ccacttctgc agaataatca gaaattggtt 85560ctttaccaga aaatccagct actataatag gctcaccgat gatcattggc aaaatcctat 85620attgtaccag attaatgaga gcatatttca tttccaataa ttctgctagt tcttgagaca 85680ttgatttatt tgatgaatct agttggttct ctagatactc taccatttct gccgcataca 85740ataacttgtt agataaaatc agggttatca aagtgtttag cgtggctaga atagtgggct 85800tgcatgtatt aaagaatgcg gtagtatgag taaaccgttt taacgaatta tatagtctcc 85860agaaatctgt ggcgttgcat acatgagccg aatgacatcg aagattgtcc aatattttta 85920atagctgctc tttgtccatt atttctatat ttgactcgca acaattgtag ataccattaa 85980tcaccgattc ctttttcgat gctggacaat agcacaattg tttagctttg gactctatgt 86040attcagaatt aatagatata tctctcaata cagattgcac tatacatttt gaaactatgt 86100caaaaattgt agaacgacgc tgttctgcag ccatttaact ttaaataatt tacaaaaatt 86160taaaatgagc atccgtataa aaatcgataa actgcgccaa attgtggcat atttttcaga 86220gttcagtgaa gaagtgtcta taaatgtaga ctcgacggat gagttaatgt atatttttgc 86280cgccttgggc ggatctgtaa acatttgggc cattatacct ctcagtgcat cagtgtttta 86340ccgaggagcc gaaaacattg tgtttaatct tcctgtgtcc aaggtaaaat cgtgtttgtg 86400tagttttcac aatgatgcca tcatagatat agaacctgat ctggaaaata atctagtaaa 86460actttctagt tatcatgtag taagtgtcga ttgtaataag gaactgatgc ctattaggac 86520agatactact atttgtctaa gtatagatca aaagaaatct tatgtgttta attttcacaa 86580gtatgaagaa aaatgttgtg gtagaaccgt cattcattta gaatggttgt tgggctttat 86640caagtgtatt agtcagcatc agcatctggc tattatgttt aaagatgaca atattattat 86700gaagactcct ggtaatactg atgcattttc cagggaatat tctatgactg aatgttctca 86760agaactacaa aagttttctt tcaaaatagc tatctcgtct ctcaacaaac tacgaggatt 86820caaaaagaga gtcaatgttt ttgaaactag aatcgtaatg gataatgacg ataacatttt 86880aggaatgttg ttttcggata gagttcaatc ctttaagatc aacatcttta tggcgttttt 86940agattaatac tttcaatgag ataaatatgg gtggcagagt aagtgttgag ctccctaaac 87000gggatccgcc tccgggagta cccactgatg agatgttatt aaacgtggat aaaatgcatg 87060acgtgatagc tcccgctaag cttttagaat atgtgcatat aggaccacta gcaaaagata 87120aagaggataa agtaaagaaa agatatccag agtttagatt agtcaacaca ggacccggtg 87180gtctttcggc attgttaaga caatcgtata atggaaccgc acccaattgc tgtcgcactt 87240ttaatcgtac tcattattgg aagaaggatg gaaagatatc agataagtat gaagagggtg 87300cagtattaga atcgtgttgg ccagacgttc acgacactgg aaaatgcgat gttgatttat 87360tcgactggtg tcagggggat acgttcgata gaaacatatg ccatcagtgg atcggttcag 87420cctttaatag gagtaataga actgtagagg gtcaacaatc gttaataaat ctgtataata 87480agatgcaaac attatgtagt aaagatgcta gtgtaccaat atgcgaatca tttttgcatt 87540atttacgcgc acacaataca gaagatagca aagagatgat cgattatatt ctaagacaac 87600agtctgcgga ctttaaacag aaatatatga gatgtagtta tcccactaga gataagttag 87660aagagtcatt aaaatatgcg gaacctcgag aatgttggga tccagagtgt tcgaatgcca 87720atgttaattt cttactaaca cgtaattata ataatttagg actttgcaat attgtacgat 87780gtaataccag cgtgaacaac ttacagatgg ataaaacttc ctcattaaga ttgtcatgtg 87840gattaagcaa tagtgataga ttttctactg ttcccgtcaa tagagcaaaa gtagttcaac 87900ataatattaa acattcgttc gacctaaaat tgcatttgat cagtttatta tctctcttgg 87960taatatggat actaattgta gctatttaaa tgggtgccgc ggcaagcata cagacgacgg 88020tgaatacact cagcgaacgt atctcgtcta aattagaaca agaagcgaac gctagtgctc 88080aaacaaaatg tgatatagaa atcggaaatt tttatatccg acaaaaccat ggatgtaacc 88140tcactgttaa aaatatgtgc tctgcggacg cggatgctca gttggatgct gtgttatcag 88200ccgctacaga aacatatagt ggattaacac cggaacaaaa agcatacgtg ccagctatgt 88260ttactgctgc gttaaacatt cagacgagtg taaacactgt tgttagagat tttgaaaatt 88320atgtgaaaca gacttgtaat tctagcgcgg tcgtcgataa caaattaaag atacaaaacg 88380taatcataga tgaatgttac ggagccccag gatctccaac aaatttggaa tttattaata 88440caggatctag caaaggaaat tgtgccatta aagcgttgat gcaattgacg actaaggcca 88500ctactcaaat agcacctaga caagttgctg gtacaggagt tcagttttat atgattgtta 88560tcggtgttat aatattggca gcgttgttta tgtactatgc caagcgtatg ttgttcacat 88620ccaccaatga taaaatcaaa cttattttag ccaataagga aaacgtccat tggactactt 88680acatggacac attctttaga acttctccga tggttattgc taccacggat atgcaaaact 88740gaaaatatat tgataatatt ttaatagatt aacatggaag ttatcgctga tcgtctagac 88800gatatagtga aacaaaatat agcggatgaa aaatttgtag attttgttat acacggtcta 88860gagcatcaat gtcctgctat acttcgacca ttaattaggt tgtttattga tatactatta 88920tttgttatag taatttatat ttttacggta cgtctagtaa gtagaaatta tcaaatgttg 88980ttggtggcgc tagtcatcac attaactatt ttttattact ttatactata atagtactag 89040actgacttct aacaaacatc tcacctgcca taaataaatg cttgatatta aagtcttcta 89100tttctaacac tattccatct gtggaaaata atactctgac attatcgcta attgacacat 89160cggtgagtga tatgcctata aagtaataat cttctttggg cacatatacc agtgtaccag 89220gttctaacaa cctatttact ggtgctcctg tagcatactt tttctttacc ttgagaatat 89280ccatcgtttg cttggtcaat agcgatatgt gattttttat caaccactcg aaaaagtaat 89340tggagtgttc atatcctcta cgggctattg tctcatggcc gtgtatgaaa tttaagtaac 89400acgactgtgg tagatttgtt ctatagagcc gattgccgca aatagataga actaccaata 89460tgtctgtaca aatgttaaac attaattgat taacagaaaa aacaatgttc gttctgggaa 89520tagaaaccag atcaaaacaa aattcgttag aatatatgcc acgtttatac atggaatata 89580aaataactac agtttgaaaa ataacagtat catttaaaca tttaacttgc ggggttaatt 89640tcacaacttt actgttttta aactgttcaa aatatagcat cgatccgtga gaaatacgtt 89700tagccgcctt taatagagga aatcccaccg cctttctgga tctcaccaac gacgatagtt 89760ctgaccagca actcatttct tcatcatcca cctgttttaa catataatag gcaggagata 89820gatatccgtc attgcaatat tccttctcgt aggcacacaa tctaatattg ataaaatctc 89880cattctcttc tctgcattta ttatcttgtt tcggtggctg attaggctgt agtcttggtt 89940taggctttgg tatatcgttg ttgaatctat tttggtcatt aaatctttca tttcttcctg 90000gtatattttt atcacctcgt ttggttggat ttttgtctat attatcgttt gtaacatcgg 90060tacgggtatt catttatcac aaaaaaaact tctctaaatg agtctactgc tagaaaacct 90120catcgaagaa gataccatat tttttgcagg aagtatatct gagtatgatg atttacaaat 90180ggttattgcc ggcgcaaaat ccaaatttcc aagatctatg ctttctattt ttaatatagt 90240acctagaacg atgtcaaaat atgagttgga gttgattcat aacgaaaata tcacaggagc 90300aatgtttacc acaatgtata atataagaaa caatttgggt ctaggagatg ataaactaac 90360tattgaagcc attgaaaact atttcttgga tcctaacaat gaagttatgc ctcttattat 90420taataatacg gatatgactg ccgtcattcc taaaaaaagt ggtaggagaa agaataagaa 90480catggttatc ttccgtcaag gatcatcacc tatcttgtgc attttcgaaa ctcgtaaaaa 90540gattaatatt tataaagaaa atatggaatc cgcgtcgact gagtatacac ctatcggaga 90600caacaaggct ttgatatcta aatatgcggg aattaatgtc ctgaatgtgt attctccttc 90660cacatccata agattgaatg ccatttacgg attcaccaat aaaaataaac tagagaaact 90720tagtactaat aaggaactag aatcgtatag ttctagccct cttcaagaac ccattaggtt 90780aaatgatttt ctgggactat tggaatgtgt taaaaaaaat attcctctaa cagatattcc 90840gacaaaggat tgattactat aaatggagaa tgttcctaat gtatacttta atcctgtgtt 90900tatagagccc acgtttaaac attctttatt aagtgtttat aaacacagat taatagtttt 90960atttgaagta ttcgttgtat tcattctaat atatgtattt tttagatctg aattaaatat 91020gttcttcatg cctaaacgaa aaatacccga tcctattgat agattacgac gtgctaatct 91080agcgtgtgaa gacgataaat taatgatcta tggattacca tggatgacaa ctcaaacatc 91140tgcgttatca ataaatagta aaccgatagt gtataaagat tgtgcaaagc ttttgcgatc 91200aataaatgga tcacaaccag tatctcttaa cgatgttctt cgcagatgat gattcatttt 91260ttaagtattt ggctagtcaa gatgatgaat cttcattatc tgatatattg caaatcactc 91320aatatctaga ctttctgtta ttattattga tccaatcaaa aaataaatta gaagccgtgg 91380gtcattgtta tgaatctctt tcagaggaat acagacaatt gacaaaattc acagactctc 91440aagattttaa aaaactgttt aacaaggtcc ctattgttac agatggaagg gtcaaactta 91500ataaaggata tttgttcgac tttgtgatta gtttgatgcg attcaaaaaa gaatcctctc 91560tagctaccac cgcaatagat cctattagat acatagatcc tcgtcgtgat atcgcatttt 91620ctaacgtgat ggatatatta aagtcgaata aagtgaacaa taattaattc tttattgtca 91680tcatgaacgg cggacatatt cagttgataa tcggccccat gttttcaggt aaaagtacag 91740aattaattag acgagttaga cgttatcaaa tagctcaata taaatgcgtg actataaaat 91800attctaacga taatagatac ggaacgggac tatggacgca tgataagaat aattttgaag 91860cattggaagc aactaaacta tgcgatgtct tggaatcaat tacagatttc tccgtgatag 91920gtatcgatga aggacagttc tttccagaca ttgttgaatt ctgtgagcgt atggcaaacg 91980aaggaaaaat agttatagta gccgcactcg atgggacatt tcaacgtaaa ccgtttaata 92040atattttgaa tcttattcca ttatctgaaa tggtggtaaa actaactgct gtgtgtatga 92100aatgctttaa ggaggcttcc ttttctaaac gattgggtga ggaaaccgag atagaaataa 92160taggaggtaa tgatatgtat caatcggtgt gtagaaagtg ttacatcgac tcataatatt 92220atatttttta tctaaaaaac taaaaataaa cattgattaa attttaatat aatacttaaa 92280aatggatgtt gtgtcgttag ataaaccgtt tatgtatttt gaggaaattg ataatgagtt 92340agattacgaa ccagaaagtg caaatgaggt cgcaaaaaaa ctgccgtatc aaggacagtt 92400aaaactatta ctaggagaat tattttttct tagtaagtta cagcgacacg gtatattaga 92460tggtgccacc gtagtgtata taggatctgc tcccggtaca catatacgtt atttgagaga 92520tcatttctat aatttaggag tgatcatcaa atggatgcta attgacggcc gccatcatga 92580tcctatttta aatggattgc gtgatgtgac tctagtgact cggttcgttg atgaggaata 92640tctacgatcc atcaaaaaac aactgcatcc ttctaagatt attttaattt ctgatgtaag 92700atccaaacga ggaggaaatg aacctagtac ggcggattta ctaagtaatt acgctctaca 92760aaatgtcatg attagtattt taaaccccgt ggcatctagt cttaaatgga gatgcccgtt 92820tccagatcaa tggatcaagg acttttatat cccacacggt aataaaatgt tacaaccttt 92880tgctccttca tattcagctg aaatgagatt attaagtatt tataccggtg agaacatgag 92940actgactcga gttaccaaat tagacgctgt aaattatgaa aaaaagatgt actaccttaa 93000taagatcgtc cgtaacaaag tagttgttaa ctttgattat cctaatcagg aatatgacta 93060ttttcacatg tactttatgc tgaggaccgt gtactgcaat aaaacatttc ctactactaa 93120agcaaaggta ctatttctac aacaatctat atttcgtttc ttaaatattc caacaacatc 93180aactgaaaaa gttagtcatg aaccaataca acgtaaaata tctagcaaaa attctatgtc 93240taaaaacaga aatagcaaga gatccgtacg cggtaataaa tagaaacgta ctactgagat 93300atactaccga tatagagtat aatgatttag ttactttaat aaccgttaga cataaaattg 93360attctatgaa aactgtgttt caggtattta acgaatcatc cataaattat actccggttg 93420atgatgatta tggagaacca atcattataa catcgtatct tcaaaaaggt cataacaagt 93480ttcctgtaaa ttttctatac atagatgtgg taatatctga cttatttcct agctttgtta 93540gactagatac tacagaaact aatatagtta atagtgtact acaaacaggt gatggtaaaa 93600agactcttcg tcttcccaaa atgttagaga cggaaatagt tgtcaagatt ctctatcgcc 93660ctaatatacc attaaaaatt gttagatttt tccgcaataa catggtaact ggagtagaga 93720tagccgatag atctgttatt tcagtcgctg attaatcaat tagtagagat gagataagaa 93780cattataata atcaataata tatcttatat cttatatctt atatcttata tcttgtttag 93840aaaaatgcta atattaaaat agctaacgct agtaatccaa tcggaagcca tttgatatct 93900ataatagggt atctaatttc ctgatttaaa tagcggacag ctatattctc ggtagctact 93960cgtttggaat cacaaacatt atttacatct aatttactat ctgtaatgga aacgtttccc 94020aatgaaatgg tacaatccga tacattgcat tttgttatat ttttttttaa agaggctggt 94080aacaacgcat cgcttcgttt acatggctcg taccaacaat aatagggtaa tcttgtatct 94140attcctatcc gtactatgct tttatcagga taaatacatt tacatcgtat atcgtctttg 94200ttagcatcac agaatgcata aatttgttcg tccgtcatga taaaaattta aagtgtaaat 94260ataactatta tttttatagt tgtaataaaa agggaaattt gattgtatac tttcggttct 94320ttaaaagaaa ctgacttgat aaaaatggct gtaatctcta aggttacgta tagtctatat 94380gatcaaaaag agattaatgc tacagatatt attattagtc atgttaaaaa tgacgacgat 94440atcggtaccg ttaaagatgg taaactaggt gctatggatg gggcattatg taagacttgt 94500gggaaaacgg aattggaatg tttcggtcac tggggtaaag taagtattta taaaactcat 94560atagttaagc ctgaatttat ttcagaaatt attcgtttac tgaatcatat atgtattcac 94620tgcggattat tgcgttcacg agaaccgtat tccgacgata ttaacctaaa agagttatcg 94680ggacacgctc ttaggagatt aaaggataaa atattatcca agaaaaagtc atgttggaac 94740agcgaatgta tgcaaccgta tcaaaaaatt actttttcaa agaaaaaggt ttgtttcgtc 94800aacaagttgg atgatattaa cgttcctaat tctctcatct atcaaaagtt aatttctatt 94860catgaaaagt tttggccatt attagaaatt catcaatatc cagctaactt attttataca 94920gactactttc ccatccctcc gttgattatt agaccggcta ttagtttttg gatagatagt 94980atacccaaag aaaccaatga attaacttac ttattaggta tgatcgttaa gaattgtaac 95040ttgaatgctg atgaacaggt tatccagaag gcggtaatag aatacgatga tattaaaatt 95100atttctaata acactaccag tatcaattta tcatatatta catccggcaa aaataatatg 95160attagaagtt atatcgtcgc ccggcgaaaa gatcagaccg ctagatctgt aattggtccc 95220agtacatcta tcaccgttaa tgaggtagga atgcccgcat atattagaaa tacacttaca 95280gaaaagatat ttgttaatgc ctttacagtg gataaagtta aacaactatt agcgtcaaac 95340caagttaaat tttactttaa taaacgatta aaccaattaa caagaatacg ccaaggaaag 95400tttattaaaa ataaaataca tttattgcct ggtgattggg tagaagtagc tgttcaagaa 95460tatacaagta ttatttttgg aagacagccg tctctacata gatacaacgt catcgcttca 95520tctatcagag ctaccgaagg agatactatc aaaatatctc ccggaattgc caactctcaa 95580aatgctgatt tcgacgggga tgaggaatgg atgatattag aacaaaatcc taaagctgta 95640attgaacaaa gtattcttat gtatccgacg acgttactca aacacgatat tcatggagcc 95700cccgtttatg gatctattca agatgaaatc gtagcagcgt attcattgtt taggatacaa 95760gatctttgtt tagatgaagt attgaacatc ttggggaaat atggaagaga gttcgatcct 95820aaaggtaaat gtaaattcag cggtaaagat atctatactt acttgatagg tgaaaagatt 95880aattatccgg gtctcttaaa ggatggtgaa attattgcaa acgacgtaga tagtaatttt 95940gttgtggcta tgaggcatct gtcattggct ggactcttat ccgatcataa gtcgaacgtg 96000gaaggtatca actttattat caagtcatct tatgttttta agagatatct atctatttac 96060ggttttgggg tgacattcaa agatctgaga ccaaattcga cgttcactaa taaattggag 96120gccatcaacg tagaaaaaat agaacttatc aaagaagcat acgccaaata tctcaacgat 96180gtaagagacg ggaaaatagt tccattatct aaagctttag aggcggacta tgtggaatcc 96240atgttatcca acttgacaaa tcttaatatc cgagagatag aagaacatat gagacaaacg 96300ctgatagatg atccagataa taacctcctg aaaatggcca aagcgggtta taaagtaaat 96360cctacagaac taatgtatat tctaggtacg tatggacaac

aaaggattga tggtgaacca 96420gcagagactc gagtattggg tagagtttta ccttactatc ttccagactc taaggatcca 96480gaaggaagag gttacattct taattcttta acaaaaggat taacgggttc tcaatattac 96540ttttcgatgc tggttgccag atctcaatct actgatatcg tctgtgaaac atcacgtacc 96600ggaacactgg ctagaaaaat cattaaaaag atggaggata tggtggtcga cggatacgga 96660caagtagtta taggtaatac gctcatcaag tacgccgcca attataccaa aattctaggc 96720tcagtatgta aacctgtaga tcttatctat ccagatgagt ccatgacttg gtatttggaa 96780attagtgctc tgtggaataa aataaaacag ggattcgttt actctcagaa acagaaactt 96840gcaaagaaga cattggcgcc gtttaatttc ctagtattcg tcaaacccac cactgaggat 96900aatgctatta aggttaagga tctgtacgat atgattcata acgtcattga tgatgtgaga 96960gagaaatact tctttacggt atctaatata gattttatgg agtatatatt cttgacgcat 97020cttaatcctt ctagaattag aattacaaaa gaaacggcta tcactatctt tgaaaagttc 97080tatgaaaaac tcaattatac tctaggtggt ggaactccta ttggaattat ttctgcacag 97140gtattgtctg agaagtttac acaacaagcc ctgtccagtt ttcacactac tgaaaaaagt 97200ggtgccgtca aacaaaaact tggtttcaac gagtttaata acttgactaa tttgagtaag 97260aataagaccg aaattatcac tctggtatcc gatgatatct ctaaacttca atctgttaag 97320attaatttcg aatttgtatg tttgggagaa ttaaatccag acatcactct tcgaaaagaa 97380acagataggt atgtagtaga tataatagtc aatagattat acatcaagag agcagaaatt 97440accgaattag tcgtcgaata tatgattgaa cgatttatct cctttagcgt cattgtaaag 97500gaatggggta tggaaacatt cattgaggat gaggataata ttagatttac tgtctatcta 97560aatttcgttg aaccagagga attgaatctt agtaagttta tgatggttct tccgggtgcc 97620gccaacaagg gcaagattag taaattcaag attcctatct ctgattatac gggttatgac 97680gacttcaatc aaacaaaaaa gctcaataag atgactgtag aactcatgaa tctaaaagaa 97740ttgggttctt tcgatttgga aaacgtcaac gtgtatcctg gagtatggaa tacatacgat 97800atcttcggta tcgaggccgc tcgtgaatac ttgtgcgaag ccatgttaaa cacctatgga 97860gaagggttcg attatctgta tcagccttgt gatcttctcg ctagtttact atgtgctagt 97920tacgaaccag aatcagtgaa taaattcaag ttcggcgcag ctagtactct taagagagct 97980acgttcggag acaataaagc attgttaaac gcggctcttc ataaaaagtc agaacctatt 98040aacgataata gtagctgcca cttttttagc aaggtcccta atataggaac tggatattac 98100aaatacttta tcgacttggg tcttctcatg agaatggaaa ggaaactatc tgataagata 98160tcttctcaaa agatcaagga aatggaagaa acagaagact tttaattctt atcaataaca 98220tatttttcta tgatctgtct tttaaacgat ggattttcca caaatgcgcc tctcaagtcc 98280ctcatagaat gatacacgta taaaaaatat agcataggca atgactcctt atttttagac 98340attagatatg ccaaaatcat agccccgctt ctatttactc ccgcagcaca atgaaccaac 98400acgggctcgt ttcgttgatc acatttagat aaaaaggcgg ttacgtcgtc aaaatattta 98460ctaatatcgg tagttgtatc atctaccaac ggtatatgaa taatattaat attagagtta 98520ggtaatgtat atttatccat cgtcaaattt aaaacatatt tgaacttaac ttcagatgat 98580ggtgcatcca tagcattttt ataatttccc aaatacacat tattggttac tcttgtcatt 98640atagtgggag atttggcttt gtgcatatct ccagttgaac gtagtagtaa gtatttatac 98700aaacttttct tatccattta taacgtacaa atggataaaa ctactttatc ggtaaacgcg 98760tgtaatttag aatacgttag agaaaaggct atagtaggcg tacaagcagc caaaacatca 98820acacttatat tctttgttat tatattggca attagtgcgc tattactctg gtttcagacg 98880tctgataatc cagtctttaa tgaattaacg agatatatgc gaattaaaaa tacggttaac 98940gattggaaat cattaacgga tagcaaaaca aaattagaaa gtgatagagg tagacttcta 99000gccgctggta aggatgatat attcgacttc aaatgtgtgg atttcggcgc ctattttata 99060gctatgcgat tggataagaa aacatatctg ccgcaagcta ttaggcgagg tactggagac 99120gcgtggatgg ttaaaaaggc ggcaaaggtc gatccatctg ctcaacaatt ttgtcagtat 99180ttgataaaac acaagtctaa taatgttatt acttgtggta atgagatgtt aaatgaatta 99240ggttatagcg gttattttat gttaccgcat tggtgttccg attttagtaa tatggaatag 99300tgttagataa atgcggtaac aaatgttcct gtaaggaacc ataacagttt agatttaacg 99360ttaaagatga gcataaacat aataaacaaa attacaatca aacctataac attaatatca 99420aacaatccaa aaaatgaaat cagtggagta gtaaacgcgt acataactcc tggataacgt 99480ttagcagctg ccgttcctat tctagaccaa aaattcggtt tcatgttttc gaaacggtat 99540tctgcaacaa gtcgaggatc gtgttctaca tatttggcgg cgttatccag tatctgccta 99600ttgatcttca tttcgttttc gattctggct atttcaaaat aaaatcccga tgatagacct 99660ccagacttta taatttcatc tacgatgttc agcgccgtag taactctaat aatataggct 99720gataagctaa catcataccc tcctgtatat gtgaatatgg catgattttt gtccattaca 99780agctcggttt taactttatt gcctgtaata atttctctca tctgtaggat atctattttt 99840ttgtcatgca ttgccttcaa gacgggacga agaaacgtaa tatcctcaat aacgttatcg 99900ttttctacaa taactacata ttctaccttt ttattttcta actcagtaaa aaaattagaa 99960tcccataggg ctaaatgtct agcgatattt cttttcgttt cctctgtaca catagtgtta 100020caaaaccctg aaaagaagtg agtatacttg tcatcatttc taatgtttcc tccagtccac 100080tgtataaacg cataatcctt gtaatgatct ggatcatcct tgactaccac aacatttctt 100140ttttctggca taacttcgtt gtcctttaca tcatcgaact tctgatcatt aatatgctca 100200tgaacattag gaaatgtttc tgatggaggt ctatcaataa ctggcacaac aataacagga 100260gttttcaccg ccgccattta gttattgaaa ttaatcatat acaactcttt aatacgagtt 100320atattttcgt ctatccattg tttcacattg acatatttcg acaaaaagat ataaaatgcg 100380tattccaatg cttctctgtt taatgaatta ctaaaatata caaacacgtc actgtctggc 100440aataaatgat atcttagaat attgtaacaa tttattttgt attgcacatg ttcgtgatct 100500atgagttctt cttcgaatgg cataggatct ccgaatctga aaacgtataa ataggagtta 100560gaataataat atttgagagt attggtaata tataaactct ttagcggtat aattagtttt 100620tttctctcaa tttctatttt tagatgtgat ggaaaaatga ctaattttgt agcattagta 100680tcatgaactc taatcaaaat cttaatatct tcgtcacacg ttagctcttt gaagttttta 100740agagatgcat cagttggttc tacagatgga gtaggtgcaa caattttttg ttctacacat 100800gtatgtactg gagccattgt tttaactata atggtgcttg tatcgaaaaa ctttaatgca 100860gatagcggaa gctcttcgcc gcgactttct acatcgtaat tgggttctaa cgccgatctc 100920tgaatggata ctagttttct aagttctaat gtgattctct gaaaatgtaa atccaattcc 100980tccggcatta tagatgtgta tacatcggta aataaaacta tagtatccaa cgatcccttc 101040tcgcaaattc tagtcttaac caaaaaatcg tatataacca cggagatggc gtatttaaga 101100gtggattctt ctaccgtttt gttcttggat gtcatatagg aaactataaa gtccgcacta 101160ctgttaagaa tgattactaa cgcaactata tagtttaaat taagcatttt ggaaacataa 101220aataactctg tagacgatac ttgactttcg aataagtttg cagacaaacg aagaaagaac 101280agacctctct taatttcaga agaaaacttt ttttcgtatt cctgacgtct agagtttata 101340tcaataagaa agttaagaat tagtcggtta atgttgtatt tcattaccca agtttgagat 101400ttcataatat tatcaaaaga catgataata ttaaagataa agcgctgact atgaacgaaa 101460tagctatatg gttcgctcaa gaatatagtc ttgttaaacg tggaaacgat aactgtattt 101520ttaatcacgt cagcggcatc taaattaaat ataggtatat ttattccaca cactctacaa 101580tatgccacac catcttcata ataaataaat tcgttagcaa aattattaat tttagtgaaa 101640tagttagcgt caactttcat agcttccttc aatctaattt gatgctcaca cggtgcgaat 101700tccactctaa catccctttt ccatgcctca ggttcatcga tctctataat atctagtttt 101760ttgcgtttca caaacacagg ctcgtctctc gcgatgagat ctgtatagta actatgtaaa 101820tgataactag atagaaagat gtagctatat agatgacgat cctttaagag aggtataata 101880actttacccc aatcagatag actgttgtta tggtcttcgg aaaaagaatt tttataaatt 101940tttccagtat tttccaaata tacgtactta acatctaaaa aatccttaat gataatagga 102000atggataatc cgtctatttt ataaagaaat acatatcgca cattatactt ttttttggaa 102060atgggaatac cgatgtgtct acataaatat gcaaagtcta aatatttttt agagaatctt 102120agttggtcca aattcttttc caagtacggt aatagatttt tcatattgaa cggtatcttc 102180ttaatctctg gttctagttc cgcattaaat gatgaaacta agtcactatt tttataacta 102240acgattacat cacctctaac atcatcattt accagaatac tgatcttctt ttgtcgtaaa 102300tacatgtcta atgtgttaaa aaaaagatca tacaagttat acgtcatttc atctgtggta 102360ttcttgtcat tgaaggataa actcgtacta atctcttctt taacagcctg ttcaaattta 102420tatcctatat acgaaaaaat agcaaccagt gtttgatcat ccgcgtcaat attctgttct 102480atcgtagtgt ataacaatcg tatatcttct tctgtgatag tcgatacgtt ataaaggttg 102540ataacgaaaa tatttttatt ttgtgaaata aagtcatcgt aggattttgg acttatattc 102600gcgtctagta gatatgcttt tatttttgga atgatctcaa ttagaatagt ctctttagag 102660tccatttaaa gttacaaaca actaggaaat tggtttatga tgtataattt ttttagtttt 102720tatagattct ttattctata cttaaaaaat gaaaataaat acaaaggttc ttgagggttg 102780tgttaaattg aaagcgagaa ataatcataa attatttcat tatcgcgata tccgttaagt 102840ttgtatcgta atggcgtggt caattacgaa taaagcggat actagtagtt tcacaaagat 102900ggctgaaatc agagctcatc taaaaaatag cgctgaaaat aaagataaaa acgaggatat 102960tttcccggaa gatgtaataa ttccatctac taagcccaaa accaaacgag ccactactcc 103020tcgtaaacca gcggctacta aaagatcaac caaaaaggag gaagtggaag aagaagtagt 103080tatagaggaa tatcatcaaa caactgaaaa aaattctcca tctcctggag tcagcgacat 103140tgtagaaagc gtggccgctg tagagctcga tgatagcgac ggggatgatg aacctatggt 103200acaagttgaa gctggtaaag taaatcatag tgctagaagc gatctttctg acctaaaggt 103260ggctaccgac aatatcgtta aagatcttaa gaaaattatt actagaatct ctgcagtatc 103320gacggttcta gaggatgttc aagcagctgg tatctctaga caatttactt ctatgactaa 103380agctattaca acactatctg atctagtcac cgagggaaaa tctaaagttg ttcgtaaaaa 103440agttaaaact tgtaagaagt aaatgcgtgc acttttttat aaagatggta aactctttac 103500cgataataat tttttaaatc ctgtatcaga cgataatcca gcgtatgagg ttttgcaaca 103560tgttaaaatt cctactcatt taacagatgt agtagtatat gaacaaacgt gggaggaggc 103620gttaactaga ttaatttttg tgggaagcga ttcaaaagga cgtagacaat acttttacgg 103680aaaaatgcat gtacagaatc gcaacgctaa aagagatcgt atttttgtta gagtatataa 103740cgttatgaaa cgaattaatt gttttataaa caaaaatata aagaaatcgt ccacagattc 103800caattatcag ttggcggttt ttatgttaat ggaaactatg ttttttatta gatttggtaa 103860aatgaaatat cttaaggaga atgaaacagt agggttatta acactaaaaa ataaacacat 103920agaaataagt cccgatgaaa tagttatcaa gtttgtagga aaggacaaag tttcacatga 103980atttgttgtt cataagtcta atagactata taaaccgcta ttgaaactga cggatgattc 104040tagtcccgaa gaatttctgt tcaacaaact aagtgaacga aaggtatacg aatgtatcaa 104100acagtttggt attagaatca aggatctccg aacgtatgga gtcaattata cgtttttata 104160taatttttgg acaaatgtaa agtccatatc tcctcttccg tcaccaaaaa agttaatagc 104220attaactatc aaacaaactg ctgaagttgt aggtcatact ccatcaattt caaaaagagc 104280ttatatggca acgactattt tagaaatggt aaaggataaa aattttttag atgtagtatc 104340taaaactacg ttcgatgaat tcctatctat agtcgtagat cacgttaaat catctacgga 104400tggatgatat agatctttac acaaataatt acaagaccga taaatggaaa tggataagcg 104460tatgaaatct ctcgcaatga cagctttctt cggagagcta aacacattag atattatggc 104520attgataatg tctatattta aacgccatcc aaacaatacc attttttcag tggataagga 104580tggtcagttt atgattgatt tcgaatacga taattataag gcttctcaat atttggatct 104640gaccctcact ccgatatctg gagatgaatg caagactcac gcatcgagta tagccgaaca 104700attggcgtgt gcggatatta ttaaagagga tattagcgaa tacatcaaaa ctactccccg 104760tcttaaacga tttataaaaa aataccgcaa tagatcagat actcgcatca gtcgagatac 104820agaaaagctt aaaatagctc tagctaaagg catagattac gaatatataa aagacgcttg 104880ttaataagta aatgaaaaaa aactagtcgt ttataataaa acacgatatg gatgccaacg 104940tagtatcatc ttctactatt gcgacgtata tagacgcttt agcgaagaat gcttcagaat 105000tagaacagag gtctaccgca tacgaaataa ataatgaatt ggaactagta tttattaagc 105060cgccattgat tactttgaca aatgtagtga atatctctac gattcaggaa tcgtttattc 105120gatttaccgt tactaataag gaaggtgtta aaattagaac taagattcca ttatctaagg 105180tacatggtct agatgtaaaa aatgtacagt tagtagatgc tatagataac atagtttggg 105240aaaagaaatc attagtgacg gaaaatcgtc ttcacaaaga atgcttgttg agactatcga 105300cagaggaacg tcatatattt ttggattaca agaaatatgg atcctctatc cgactagaat 105360tagtcaatct tattcaagca aaaacaaaaa actttacgat agactttaag ctaaaatatt 105420ttctaggatc cggtgcccag tctaaaagtt ctttattaca cgctattaat catccaaagt 105480caaggcctaa tacatctctg gaaatagaat tcacacctag agacaatgaa acagttccat 105540atgatgaact aataaaggaa ttgacgactc tatcacgtca tatatttatg gcttctccag 105600agaatgtaat tctttctccg cctattaacg cgcctataaa aacctttatg ttgcctaaac 105660aagatatagt aggtttggat ctggaaaatc tatatgccgt aactaagact gacggcattc 105720ctataactat cagagttaca tcaaacgggt tgtattgtta ttttacacat cttgggtata 105780ttattagata tccagttaag agaataatag attccgaagt agtagtcttt ggtgaggcag 105840ttaaggataa gaactggacc gtatatctta ttaagctaat agagcctgtg aatgctatca 105900gtgatagact agaagaaagt aagtatgttg aatctaaact agtggatatt tgtgatcgga 105960tagtattcaa gtcaaagaaa tacgaaggtc cgtttactac aactagtgaa gtcgtcgata 106020tgttatctac atatttacca aagcaaccag aaggtgttat tctgttctat tcaaagggac 106080ctaaatctaa cattgatttt aaaattaaaa aggaaaatac tatagaccaa actgcaaatg 106140tagtatttag gtacatgtcc agtgaaccaa ttatctttgg agaatcgtct atctttgtag 106200agtataagaa atttagcaac gataaaggct ttcctaaaga atatggttct ggtaagattg 106260tgttatataa cggcgttaat tatctaaata atatctattg tttggaatat attaatacac 106320ataatgaagt gggtattaag tccgtggttg tacctattaa gtttatagca gaattcttag 106380ttaatggaga aatacttaaa cctagaattg ataaaaccat gaaatatatt aactcagaag 106440attattatgg aaatcaacat aatatcatag tcgaacattt aagagatcaa agcatcaaaa 106500taggagatat ctttaacgag gataaactat cggatgtggg acatcaatac gccaataatg 106560ataaatttag attaaatcca gaagttagtt attttacgaa taaacgaact agaggaccgt 106620tgggaatttt atcaaactac gtcaagactc ttcttatttc tatgtattgt tccaaaacat 106680ttttagacga ttccaacaaa cgaaaggtat tggcgattga ttttggaaac ggtgctgacc 106740tggaaaaata cttttatgga gagattgcgt tattggtagc gacggatccg gatgctgatg 106800ctatagctag aggaaatgaa agatacaaca aattaaactc tggaattaaa accaagtact 106860acaaatttga ctacattcag gaaactattc gatccgatac atttgtctct agtgtcagag 106920aagtattcta ttttggaaag tttaatatca tcgactggca gtttgctatc cattattctt 106980ttcatccgag acattatgct accgtcatga ataacttatc cgaactaact gcttctggag 107040gcaaggtatt aatcactacc atggacggag acaaattatc aaaattaaca gataaaaaga 107100cttttataat tcataagaat ttacctagta gcgaaaacta tatgtctgta gaaaaaatag 107160ctgatgatag aatagtggta tataatccat caacaatgtc tactccaatg actgaataca 107220ttatcaaaaa gaacgatata gtcagagtgt ttaacgaata cggatttgtt cttgtagata 107280acgttgattt cgctacaatt atagaacgaa gtaaaaagtt tattaatggc gcatctacaa 107340tggaagatag accgtctaca aaaaactttt tcgaactaaa tagaggagcc attaaatgtg 107400aaggtttaga tgtcgaagac ttacttagtt actatgttgt ttatgtcttt tctaagcggt 107460aaataataat atggtatggg ttctgatatc cccgttctaa atgcattaaa taattccaat 107520agagcgattt ttgttcctat aggaccttcc aactgtggat actctgtatt gttaatagat 107580atattaatac ttttgtcggg taacagaggt tctacgtctt ctaaaaataa aagttttata 107640acatctggcc tgttcataaa taaaaacttg gcgattctat atatactctt attatcaaat 107700ctagccattg tcttatagat gtgagctact gtaggtgtac catttgattt tctttctaat 107760actatatatt tctctcgaag aagttcttgc acatcatctg ggaataaaat actactgttg 107820agtaaatcag ttattttttt tatatcgata ttgatggaca tttttatagt taaggataat 107880aagtatccca aagtcgataa cgacgataac gaagtattta tacttttagg aaatcacaat 107940gactttatca gattaaaatt aacaaaatta aaggagcatg tatttttttc tgaatatatt 108000gtgactccag atacatatgg atctttatgc gtcgaattaa atgggtctag ttttcagcac 108060ggtggtagat atatagaggt ggaggaattt atagatgctg gaagacaagt tagatggtgt 108120tctacatcca atcatatatc taaagatata cccgaagata tgcacactga taaatttgtc 108180atttatgata tatacacttt tgacgctttc aagaataaac gattggtatt cgtacaggtg 108240cctccgtcgt taggagatga tagtcatttg actaatccgt tattgtcacc gtattatcgt 108300aattcagtag ccagacaaat ggtcaatgat atgattttta atcaagattc atttttaaaa 108360tatttattag aacatctgat tagaagccac tatagagttt ctaaacatat aacaatagtt 108420agatacaagg ataccgaaga attaaatcta acgagaatat gttataatag agataagttt 108480aaggcgtttg tattcgcttg gtttaacggc gtttcggaaa atgaaaaggt actagatacg 108540tataaaaagg tatctaattt gatataatga attcagtgac tgtatcacac gcgccatata 108600ctattactta tcacgatgat tgggaaccag taatgagtca attggtagag ttttataacg 108660aagtagccag ttggctgcta cgagacgaga cgtcgcctat tcctgataag ttctttatac 108720agttgaaaca accgcttaga aataaacgag tatgtgtgtg tggtatagat ccgtatccga 108780aagatggaac tggtgtaccg ttcgaatcac caaattttac aaaaaaatca attaaggaga 108840tagcttcatc tatatctaga ttaaccggag taattgatta taaaggttat aaccttaata 108900taatagacgg ggttataccc tggaattatt acttaagttg taaattagga gaaacaaaaa 108960gtcacgcgat ttactgggat aaaatttcta agttactgct gcagcatata actaaacacg 109020ttagtgttct ttattgtttg ggtaaaacag atttctcgaa tatacgggcc aagttagaat 109080ccccggtaac taccatagtc ggatatcatc cagcggctag agaccgccaa ttcgagaaag 109140atagatcatt tgaaattatc aacgttttac tggaattaga caacaaggca cctataaatt 109200gggctcaagg gtttatttat taatgcttta gtgaaatttt aacttgtgtt ctaaatggat 109260gcggctatta gaggtaataa tgttatcttt gttcttaaga ctataggtgt cccgtcagcg 109320tgcagacaaa atgaagatcc aagatttgta gaagcattta aatgcgacga gttagaaaga 109380tatattgaga ataatccaga atgtacacta ttcgaaagtc ttagggatga ggaagcatac 109440tctatagtca gaattttcat ggatgtagat ttagacgcgt gtctagacga aatagattat 109500ttaacggcta ttcaagattt tattatcgag gtgtcaaact gtgtagctag attcgcgttt 109560acagaatgcg gcgccattca tgaaaatgta ataaaatcca tgagatctaa tttttcattg 109620actaagtcta caaatagaga taaaacaagt tttcatatta tctttttaga cacgtatacc 109680actatggata cattgatagc tatgaaacga acactattag aattaagtag atcatctgaa 109740aatccactaa ccagatcgat agacactgcc gtatatagga gaaaaacaac tcttcgggtt 109800gtaggtacta ggaaaaatcc aaattgcgac actattcatg taatgcaacc accgcatgat 109860aatatagaag attacctatt cacttacgtg gatatgaaca acaatagtta ttacttttct 109920ctacaacgac gattggagga tttagttcct gataagttat gggaaccagg gtttatttca 109980ttcgaagacg ctataaaaag agtttcaaaa atattcatta attctataat aaactttaat 110040gatctcgatg aaaataattt tacaacggta ccactggtca tagattacgt aacaccttgt 110100gcattatgta aaaaacgatc gcataaacat ccgcatcaac tatcgttgga aaatggtgct 110160attagaattt acaaaactgg taatccacat agttgtaaag ttaaaattgt tccgttggat 110220ggtaataaac tgtttaatat tgcacaaaga attttagaca ctaactctgt tttattaacc 110280gaacgaggag accatatagt ttggattaat aattcatgga aatttaacag cgaagaaccc 110340ttgataacaa aactaatttt gtcaataaga catcaactac ctaaggaata ttcaagcgaa 110400ttactctgtc caagaaaacg aaagactgta gaagctaaca tacgagacat gttagtagat 110460tcagtagaga ccgataccta tccggataaa cttccgttta aaaatggtgt attggacctg 110520gtagacggaa tgttttactc tggagatgat gctaaaaaat atacgtgtac tgtatcaacc 110580ggatttaaat ttgacgatac aaagttcgtc gaagacagtc cagaaatgga agagttaatg 110640aatatcatta acgatatcca accattaacg gatgaaaata agaaaaatag agagctatat 110700gaaaaaacat tatctagttg tttatgtggt gctaccaaag gatgtttaac attctttttt 110760ggagaaactg caactggaaa gtcgacaacc aaacgtttgt taaagtctgc tatcggtgac 110820ctgtttgttg agacgggtca aacaatttta acagatgtat tggataaagg acctaatcca 110880tttatcgcta acatgcattt gaaaagatct gtattctgta gcgaactacc tgattttgcc 110940tgtagtggat caaagaaaat tagatctgac aatattaaaa agttgacaga accttgtgtc 111000attggaagac cgtgtttctc caataaaatt aataatagaa accatgcgac aatcattatc 111060gatactaatt acaaacctgt ctttgatagg atagataacg cattaatgag aagaattgcc 111120gtcgtgcgat tcagaacaca cttttctcaa ccttctggta gagaggctgc tgaaaataat 111180gacgcgtacg ataaagtcaa actattagac gaggggttag atggtaaaat acaaaataat 111240agatatagat ttgcatttct atacttgttg gtgaaatggt acagaaaata tcatgttcct 111300attatgaaac tatatcctac accggaagag attcctgact ttgcattcta tctcaaaata 111360ggtactctgt tagtatctag ctctgtaaag catattccat taatgacgga cctctccaaa 111420aagggatata tattgtacga taatgtggtc actcttccgt

tgactacttt ccaacagaaa 111480atatccaagt attttaattc tagactattt ggacacgata tagagagctt catcaataga 111540cataagaaat ttgccaatgt tagtgatgaa tatctgcaat atatattcat agaggatatt 111600tcatctccgt aaatatatgc tcatatattt atagaagata tcacatatct aaatgaatac 111660cggaatcata gatttatttg ataatcatgt tgatagtata ccaactatat tacctcatca 111720gttagctact ctagattatc tagttagaac tatcatagat gagaacagaa gcgtgttatt 111780gttccatatt atgggatcag gtaaaacaat aatcgctttg ttgttcgcct tggtagcttc 111840cagatttaaa aaggtttaca ttctagtgcc gaacatcaac atcttaaaaa ttttcaatta 111900taatatgggt gtagctatga acttgtttaa tgacgaattc atagctgaaa atatctttat 111960tcattccaca acaagttttt attctcttaa ttataacgat aacgtcatta attataacgg 112020attatctcgc tacaataact ctatttttat cgttgatgag gcacataata tctttgggaa 112080taatactgga gaacttatga ccgtgataaa aaataaaaac aagattcctt ttttactatt 112140gtctggatct cccattacta acacacctaa tactctgggt catattatag atttaatgtc 112200cgaagagacg atagattttg gtgaaattat tagtcgtggt aagaaagtaa ttcagacact 112260tcttaacgaa cgaggtgtga atgtacttaa ggatttgctt aaaggaagaa tatcatatta 112320cgaaatgcct gataaagatc taccaacgat aagatatcac ggacgtaagt ttctagatac 112380tagagtagta tattgtcaca tgtctaaact tcaagagaga gattatatga ttactagacg 112440acagctatgt tatcatgaaa tgtttgataa aaatatgtat aacgtgtcaa tggcagtatt 112500gggacaactt aatctgatga ataatttaga tactttattt caggaacagg ataaggaatt 112560gtacccaaat ctgaaaataa ataatggcgt gttatacgga gaagaattgg taacgttaaa 112620cattagttcc aaatttaagt actttattaa tcggatacag acactcaacg gaaaacattt 112680tatatacttt tctaattcta catatggcgg attggtaatt aaatatatca tgctcagtaa 112740tggatattct gaatataatg gttctcaggg aactaatcca catatgataa acggcaaacc 112800aaaaacattt gctatcgtta ctagtaaaat gaaatcgtct ttagaggatc tattagatgt 112860gtataattct cctgaaaacg atgatggtag tcaattgatg tttttgtttt cgtcaaacat 112920tatgtccgaa tcctatactc tgaaagaggt aaggcatatt tggtttatga ctatcccaga 112980tactttttct caatacaacc aaattcttgg acgatctatt agaaaattct cttacgccga 113040tatttctgaa ccagttaatg tatatctttt agccgccgta tattccgatt tcaatgacga 113100agtgacgtca ttaaacgatt acacacagga tgaattaatt aatgttttac catttgacat 113160caaaaagctg ttatatctaa aatttaagac gaaagaaacg aatagaatat actctattct 113220tcaagagatg tctgaaacgt attctcttcc accacatcca tcaattgtaa aagttttatt 113280gggagaattg gtcagacaat ttttttataa taattctcgt attaagtata acgataccaa 113340gttacttaaa atggttacat cagttataaa aaataaagaa gacgctagga attacataga 113400tgatattgta aacggtcact tctttgtatc gaataaagta tttgataaat ctcttttata 113460caaatacgaa aacgatatta ttacagtacc gtttagactt tcctacgaac catttgtttg 113520gggagttaac tttcgtaaag aatataacgt ggtatcttct ccataaaact gatgagatat 113580ataaagaaat aaatgtcgag ctttgttacc aatggatacc tttccgttac attggaacct 113640catgagctga cgttagacat aaaaactaat attaggaatg ccgtatataa gacgtatctc 113700catagagaaa ttagtggtaa aatggccaag aaaatagaaa ttcgtgaaga cgtggaatta 113760cctctcggcg aaatagttaa taattctgta gttataaacg ttccgtgtgt aataacctac 113820gcgtattatc acgttgggga tatagtcaga ggaacattaa acatcgaaga tgaatcaaat 113880gtaactattc aatgtggaga tttaatctgt aaactaagta gagattcggg tactgtatca 113940tttagcgatt caaagtactg cttttttcga aatggtaatg cgtatgacaa tggcagcgaa 114000gtcactgccg ttctaatgga ggctcaacaa ggtatcgaat ctagttttgt ttttctcgcg 114060aatatcgtcg actcataaga aagagaatag cggtaagtat aaacacgaat actatggcaa 114120taattgcgaa tgttttattc tcttcgatat atttttgata atatgaaaaa catgtctctc 114180tcaaatcgga caaccatctc ataaaatagt tatctcgcgc tggcgaggtg gttgctgctc 114240gtataatctc cccagaataa tatacttgcg tgtcgtcgtt caatttatac ggatttctat 114300agttctctgt tatataatgc ggttttctat catgattaga cgacgacaat agtgttctaa 114360atttagatag ttgatcagaa tgaatgttta ttggcgttgg aaaaattatc catacagcgt 114420ctgcagagtg gttgatagtt gttcctagat atgtaaaata atccaactta ctaggcagca 114480aattgtctag ataaaatact gaatcaaacg gtgcagacgt attggcggat ctaatggaat 114540ccaattgatt aactatcttt tgaaaatata catttttatg atccaatact tgtaagaata 114600tagaaataat gataagtcca tcatcgtgtt tttttgcctc ttcataagaa ctatattttt 114660tcttattcca atgaacaaga ttaatctctc cagagtattt gtacacatct atcaagtgat 114720tggatccata atcgtcttcc tttccccaat atatatgtag tgatgataac acatattcat 114780tggggagaaa ccctccactt atatatcctc ctttaaaatt aatccttact agttttccag 114840tgttctggat agtggttggt ttcgactcat tataatgtat gtctaacggc ttcaatcgcg 114900cgttagaaat tgctttttta gtttctatat taataggaga tagttgttgc ggcatagtaa 114960aaatgaaatg ataactgttt aaaaatagct cttagtatgg gaattacaat ggatgaggaa 115020gtgatatttg aaactcctag agaattaata tctattaaac gaataaaaga tattccaaga 115080tcaaaagaca cgcatgtgtt tgctgcgtgt ataacaagtg acggatatcc gttaatagga 115140gctagaagaa cttcattcgc gttccaggcg atattatctc aacaaaattc agattctatc 115200tttagagtat ccactaaact attacggttt atgtactaca atgaactaag agaaatcttt 115260agacggttga gaaaaggttc tatcaacaat atcgatcctc actttgaaga gttaatatta 115320ttgggtggta aactagataa aaaggaatct attaaagatt gtttaagaag agaattaaaa 115380gaggaaagtg atgaacgtat aacagtaaaa gaatttggaa atgtaattct aaaacttaca 115440acacgggata aattatttaa taaagtatat ataagttatt gcatggcgtg ttttattaat 115500caatcgttgg aggatttatc gcatactagt atttacaatg tagaaattag aaagattaaa 115560tcattaaatg attgtattaa cgacgataaa tacgaatatc tgtcttatat ttataatatg 115620ctagttaata gtaaatgaac ttttacagat ctagtataat tagtcagatt attaagtata 115680atagacgact agctaagtct attatttgcg aggatgactc tcaaattatc acactcacgg 115740cattcgttaa ccaatgccta tggtgtcata aacgagtatc cgtgtccgct attttattaa 115800ctactgataa caaaatatta gtatgtaaca gacgagatag ttttctctat tctgaaataa 115860ttagaactag aaacatgttt agaaagaaac gattatttct gaattattcc aattatttga 115920acaaacagga aagaagtata ctatcgtcat ttttttctct agatccagct actactgata 115980atgatagaat agacgctatt tatccgggtg gcatacccaa aaggggtgag aatgttccag 116040agtgtttatc cagggaaatt aaagaagaag ttaatataga caattctttt gtattcatag 116100acactcggtt ttttattcat ggcatcatag aagataccat tattaataaa ttttttgagg 116160taatcttctt tgtcggaaga atatctctaa cgagtgatca aatcattgat acatttaaaa 116220gtaatcatga aatcaaggat ctaatatttt tagatccgaa ttcaggtaat ggactccaat 116280acgaaattgc aaaatatgct ctagatactg caaaacttaa atgttacggc catagaggat 116340gttattacga atcattaaaa aaattaactg aggatgattg attagaaaat ataaattaat 116400ttaccatcgt gtatttttat aacgggattg tccggcatat catgtagata gttaccgtct 116460acatcgtata ctcgaccatc tacgccttta aatcctctat ttattgacat taatctatta 116520gaattggaat accaaatatt agtaccctca attagtttat tggtaatatt ttttttagac 116580gatagatcga tggctcttga aaccaaggtt ttccaaccgg actcattgtc gatcggtgag 116640aagtcttttt cattagcatg aatccattct aatgatgtat gtttaaacac tctaaacaat 116700tggacaaatt cttttgattt gctttgaatg atttcaaata ggtcttcgtc tacagtaggc 116760ataccattag ataatctagc cattataaag tgcacgttta catatctacg ttctggagga 116820gtaagaacgt gactattgag acgaatggct cttcctacta tctgacgaag agacgcctcg 116880ttccatgtca tatctaaaat gaagatatca ttaattgaga aaaaactaat accctcgcct 116940ccactagaag agaatacgca tgttttaatg cattctccgt tagtgtttga ttcttggtta 117000aactcagcca ccgccttgat tctagtatct tttgttctag atgagaactc tatattagag 117060ataccaaaga ctttgaaata tagtaataag atttctattc ctgactgatt aacaaatggt 117120tcaaagacta gacatttacc atgggatgct aatattccca aacatacatc tataaatttg 117180acgcttttct cttttaattc agtaaataga gagatatcag ccgcactagc atcccctttc 117240aatagttctc cctttttaaa ggtatctaat gcggatttag aaaactctct atctcttaat 117300gaatttttaa aatcattata tagtgttgct atctcttgcg cgtattcgcc cggatcacga 117360ttttgtcttt caggaaagct atcgaacgta aacgtagtag ccatacgtct cagaattcta 117420aatgatgata tacctgtttt tatttcagcg agtttagcct tttgataaat ttcttcttgc 117480tttttcgaca tattaacgta tcgcattaat actgttttct tagcgaatga tgcagaccct 117540tctacgtcat caaaaataga aaactcgtta ttaactatgt acgaacatag gcctcctagt 117600ttggagacta attctttttc atcgactaga cgtttattct caaatagcga ttggtgttgt 117660aaggatcctg gtcgtagtaa gttaaccaac atggtgaatt cttgcacact attgacgata 117720ggtgtagccg ataaacaaat catcttatgg ttttttaacg caatggtctt agataaaaaa 117780ttatatactg aacgagtagg acggatctta ccatcttctt tgattaatga tttagaaatg 117840aagttatgac attcatcaat gatgacgcat attctactct tggcattaat agttttgata 117900ttagtaaaaa atttatttct aaaattttga tcatcgtaat taataaaaat acaatccttc 117960gttatctctg gagcgtatct gagtatagtg ttcatccaag gatcttctat caaagccttt 118020ttcaccaata agataatagc ccaattcgta taaatatcct taagatgttt gagaatatat 118080acagtagtca ttgttttacc gacacccgtt tcatggaaca ataaaagaga atgcatactg 118140tctaatccta agaaaactct tgctacaaaa tgttgataat ccttgaggcg tactacgtcc 118200gaccccatca tttcaacggg catattagta gttctgcgca atgcataatc gatataggcc 118260gcgtgtgatt tactcattta tgagtgataa gtaataacta tgttttaaaa atcacagcag 118320tagtttaact agtcttctct gatgtttgtt ttcgatactt tttgaatcag aagtcatact 118380agaataaagc aacgagtgaa cgtaatagag agcttcgtat actctattcg aaaactctaa 118440gaacttatta atgaattccg tatccactgg attgtttaaa atactaaatt gaacactgtt 118500cacatccttc caagaagaag acttagtgac ggacttaaca tgagacataa ataaatccaa 118560atttttttta caaacatcac tagccaccat aatggcgcta tctttcaacc agctatcgct 118620tacgcatttt agcagtctaa catttttaaa gagactacaa tatattctca tagtatcgat 118680tacacctcta ccgaatagag taggaagttt aataatacaa tatttttcgt ttacaaaatc 118740aaataatggt cgaaacacgt cgaaggttaa catcttataa tcgctaatgt atagattgtt 118800ttcagtgaga tgattattag atttaatagc atctcgttca cgtttgaaca gtttattgcg 118860tgcgctgagg tcggcaacta cggcgtccgc tttagtactc ctcccataat actttacgct 118920attaatcttt aaaatttcat agactttatc tagatcgctt tctggtaaca tgatatcatg 118980tgtaaaaagt tttaacatgt cggtcggcat tctatttaga tcattaactc tagaaatctg 119040aagaaagtaa ttagctccgt attccagact aggtaatggg cttttaccta gagacagatt 119100aagttctggc aatgtttcat aaaatggaag aaggacatgc gttccctccc ggatattttt 119160tacaatttca tccatttaca actctatagt ttgttttcat tattattagt tattatctcc 119220cataatcttg gtaatactta ccccttgatc gtaagatacc ttatacaggt cattacatac 119280aactaccaat tgtttttgta cataatagat tggatggttg acatccatgg tggaataaac 119340tactcgaaca gatagtttat ctttccccct agatacatta gccgtaatag ttgtcggcct 119400aaagaatatc tttggtgtaa agttaaaagt tagggttctt gttccattat tgctttttgt 119460cagtagttca ttataaattc tcgagatggg tccgttctct gaatatagaa catcatttcc 119520aaatctaact tctagtctag aaataatatc ggtcttattc ttaaaatcta ttcccttgat 119580gaagggatcg ttaatgaaca aatccttggc ctttgattcg gctgatctat tatctccgtt 119640atagacgtta cgttgactag tccaaagact tacaggaata gatgtatcga tgatgttgat 119700actatgtgat atgtgagcaa agattgttct cttagtggca tcactatatg ttccagtaat 119760ggcggaaaac tttttagaaa tgttatatat aaaagaattt tttcgtgttc caaacattag 119820cagattagta tgaagataaa cactcatatt atcaggaaca ttatcaattt ttacatacac 119880atcagcatct tgaatagaaa cgataccatc ttctggaacc tctacgatct cggcagactc 119940cggataacca gtcggtggac catcgctaac aataactaga tcatccaaca atctactcac 120000atatgcatct atataatctt tttcatcttg tgagtaccct ggatacgaaa taaatttatt 120060atccgtattt ccataataag gtttagtata aacagagaga gatgttgccg catgaacttc 120120agttacagtc gccgttggtt ggtttatttg acctattact ctcctaggtt tctctataaa 120180cgatggttta atttgtacat tcttaaccat atatccaata aagctcaatt caggaacata 120240aacaaattct ttgttgaacg tttcaaagtc gaacgaagag tcacgaataa cgatatcgga 120300tactggattg aaggtcaccg ttacggtaat ttttgaatcg gatagtttaa gactgctgaa 120360tgtatcttcc acatcaaacg gagttttaat ataaacgtat actgtagatg gttctttaat 120420agtgtcatta ggagttaggc caatagaaat atcattaagt tcactagaat atccagagtg 120480tttcaaagca attgtattat tgatacaatt attatataat tcttcgccct caatttccca 120540aataacaccg ttacacgaag agatagatac gtgattaata catttatatc caacatatgg 120600tacgtaaccg aatcttccca tacctttaac ttctggaagt tccaaactca gaaccaaatg 120660attaagcgca gtaatatact gatccctaat ttcgaagcta gcgatagcct gattgtctgg 120720accatcgttt gtcataactc cggatagaga aatatattgc ggcatatata aagttggaat 120780ttgactatcg actgcgaaga cattagaccg tttaatagag tcatccccac cgatcaaaga 120840attaatgata gtattattca ttttctattt aaaatggaaa aagcttacaa taaactccgt 120900agagaaatat ctataatttg tgagttttcc ttaaagtaac agcttccgta aacgccgtct 120960ttatctctta gtaagtttat tgtatttatg accttttcct tatcttcata gaatactaaa 121020ggcaacaaag aaatttttgg ttcttctcta agagctacgt gagacttaac catagacgcc 121080aacgaatccc tacatatttt agaacagaaa taccctactt caccaccctt gtatgtctca 121140atactaatag gtctaaaaac caaatcttga ttacaaaacc aacacttatc aattacacta 121200tttgtcttaa tagacacatc tgccatagat ttataatact ttggtagtat acaagcgagt 121260gcttcttctt tagcgggctt aaagactgct ttaggtgctg aaataaccac atctggaagg 121320cttactcgct tagccattta attacggaac tattttttta tacttctaat gagcaagtag 121380aaaacctctc atctacaaaa acgtactcgt gtccataatc ctctaccata gtaacacgtt 121440ttttagatct catatgtgct aaaaagtttt cccatactaa ttggttacta ttatttttcg 121500tataattttt aacagtttga ggttttagat ttttagttac agaagtgata tcgaatattt 121560tatccaaaaa gaatgaataa ttaattgtct tagaaggagt gttttcttgg caaaagaata 121620ccaagtgctt aaatatttct actacttcat taatcttttc tgtactcaga ttcagtttct 121680catcttttac ttgattgatt atttcaaaga ctaacttata atccttttta tttattctct 121740cgttagcctt aagaaaacta gatacaaaat ttgcatctac atcatccgtg gatatttgat 121800ttttttccat gatatccaag agttccgaga taatttctcc agaacattga tgagacaata 121860atctccgcaa tacatttctc aaatgaataa gtttattaga cacgtggaag tttgactttt 121920tttgtacctt tgtacatttt tgaaataccg actcgcaaaa aatacaatat tcatatcctt 121980gttcagatac tataccgttg tgtctacaac cgctacataa tcgtagattc atgttaacac 122040tctacgtatc tcgtcgtcca atattttata taaaaacatt ttatttctag acgttgccag 122100aaaatcctgt aatattttta gttttttggg ctgtgaataa agtatcgccc taatatggtt 122160accgtcctcc gccaatatag tagttaaatt atccgcacat gcagaagaac accgcttagg 122220cggattcagt acaatgttat atttttcgta ccaactcatt taaatatcat aatctaaaat 122280agttctgtaa tatgtctagc gctaatatat tgatcataat cctgtgcata aattaagata 122340caacaatgtc tcgaaatcat cgacatggct tcttccatag ttagaagatc gtcgtcaaag 122400ttagcaacgt gattcatcaa catttgctgt tttgaggcag caaatactga accgtcgcca 122460ttcaaccatt cataaaaacc atcgtctgaa tccattgata atttcttgta ctggtttttg 122520agagctcgca tcaatctagc atttctagct cccggattga aaacagaaag aggatcgtac 122580atccagggtc cattttctgt aaatagaatc gtataatgtc ccttcaagaa gatatcagac 122640gatccacaat caaagaattg gtctccgagt ttgtaacaga cagcggactt taacctatac 122700atgataccgt ttagcataat ttctggtgat acgtcaatcg gagtatcatc tattagagat 122760ctaaagccgg tgtaacattc tccaccaaac atattcttat tctgacgtcg ttctacataa 122820aacatcattg ctccattaac gataacaggg gaatgaacag cactacccat cacattagtt 122880cccaatggat caatgtgtgt aactccagaa catcttccat agcctatgtt aggaggagcg 122940aacaccactc ttccactatt gccatcgaat gccatagaat aaatatcctt ggaattgata 123000gaaatcggac tgtcggatgt tgtgatcatc ttcataggat taacaactat gtatggtgcc 123060gcctgaagtt tcatatcgta actgatgccg tttataggtc tagccacaga aaccaacgta 123120ggtctaaatc caactataga caaaatagaa gccaatatct gttcctcatc tgtcataact 123180tgagagcatc cagtatgaat aatcttcatt agatggggat ctaccgcatc atcatcgtta 123240caataaaaaa ttcccattct aatgttcata attgcttttc taatcatggt atgcatgttt 123300gctctctgaa tctctgtgga aattagatct gatacacctg taatcactat cggattatcc 123360tccgtaagac gattaaccaa caacatataa ttataagact ttacttttct aaattcataa 123420agttgctgga ttaggctata ggtgtctcca tgtacatacg cgttctcgag cgcaggaagt 123480ttaataccga atagtgccat cagaatagga tgaatatagt aattagtttc tggttttcta 123540taaataaaag acaaatcttg tgaactagac atatcggtaa aatgcatgga ttggaatcgt 123600gtagtcgaca gaagaatatg atgattagat ggagagtata ttttatctaa ctctttgagt 123660tggtcaccga ttctaggact agctcgagaa tgaataagta ctaaaggatg agtacatttc 123720acagaaacac tagcattgtt caatgtgctc tttacatggg taaggagttg aaatagctcg 123780tttctatttg ttctgacaat atttagttta ttcataatgt taagcatatc ctgaatagta 123840aagttagatg tgtcatactt gttagtagtt agatatttag caattgcatt cccatcattt 123900ctcaatctcg tactccaatc atgcgtggat gctacttcgt cgatggaaac catacaatcc 123960tttttggtag tctgttgagc ttgatcattt cctgcacgtt taggtttggt acgttgattt 124020ctagcccctg cggatataaa gtcatcgtct acaatttggg acaatgaatt gcatacacta 124080caagacaaag atttatcaga agtgtgaata tgatcttcat ctaccaaaga aagagtttga 124140ttagtataac tagattttag tcctgcgtta gatgttaaaa aaacatcgct attgaccacg 124200gcttccatta tttatattcg tagtttttac tcgaaagcgt gattttaata tccaatctta 124260ttacttttgg aatcgttcaa aacctttgac taattgtaga atttgattta ttgccctacg 124320cgtatactcc cttgcatcat atacgttcgt caccagatcg tttgtttcgg cctgaagttg 124380gtgcatatct ctttcaacat tcgacatgag atccttaagg gccatatcgt ctagattttg 124440ttgagatgct gctcctggat ttggattttg ttgtgctgtt gtacatactg taccaccagt 124500aggtgtagga gtacatacag tggccacaat aggaggttga ggaggtgtaa ccgttggagt 124560agtacaagaa atatttccat ccgattgttg tgtacatgta gttgttggta acgtctgaga 124620aggttgggta gatggcggtg tcgtcgtctt ttgatcttta ttaaatttag agataatatc 124680ctgaacagca ttgctcggcg tcaacgctgg aaggagtgaa ctcgccggcg catcagtatc 124740ttcagacagc caatcaaaaa gattagacat atcagatgat gtattagttt gttgtcgtgg 124800ttttggtgta ggagcagtac tactaggtag aagaatagga gccggtgtag ctgttggaac 124860cggctgtgga gttatatgaa tagttggttg tagcggttgg ataggctgtc tgctggcggc 124920catcatatta tctctagcta gttgttctcg caactgtctt tgataatacg actcttgaga 124980ctttagtcct atttcaatcg cttcatcctt tttcgtatcc ggatcctttt cttcagaata 125040atagattgac gactttggtg tagaggattc tgccagcctc tgtgagaact tgttaaagaa 125100gtccatttaa ggctttaaaa ttgaattgcg attataagat taaatggcag acacagacga 125160tattatcgac tatgaatccg atgatctcac cgaatacgag gatgatgaag aagaggaaga 125220agatggagag tcactagaaa ctagtgatat agatcccaaa tcttcttata agattgtaga 125280atcagcatcc actcatatag aagatgcgca ttccaatctt aaacatatag ggaatcatat 125340atctgctctt aaacgacgct atactagacg tataagtcta tttgaaatag cgggtataat 125400agcagaaagc tataacttgc ttcaacgagg aagattacct ctagtttcag aattttctga 125460cgaaacgatg aagcaaaata tgctacatgt aattatacaa gagatagagg agggttcttg 125520tcctatagtc atcgaaaaga acggagaatt gttgtcggta aacgattttg acaaagatgg 125580tctaaaattc catctagact atattatcaa aatttggaaa cttcaaaaac gatattagaa 125640tttatacgaa tatcgttctc taaatgtcac aatcaagtct cgcatgttca gcaatttatt 125700gtcgtacttt atatcgtgtt cattaacgat atcttgcaaa atagtaatga ttctatcttc 125760cttcgataga tattcttcag agattattgt cttatattct ttcttgttat ccgatatgaa 125820tttgataaga ctttgaacat tattgatacc cgtctgttta attttttcta cagatatttt 125880agttttggca gattctatcg tatctgtcaa tagacatcca acatcgacat tcgacgtcaa 125940ttgtctataa atcagagtat aaattttaga aataacatta gcgaattgtt gtgcgttgat 126000gtcgttattc tgaaacagta tgattttagg tagcattttc ttaacaaaga gaacgtattt 126060attgttactc agttgaacag atgatatatc cagattacta acgcatctga ttccgtatac 126120caaactttca gaagaaatgg tgtacaattg tttgtattca ttcaatgtct ctttttcaga 126180aattagttta gagtcgaata ctgcaataat tttcaagaga tagttttcat cagataagat 126240tttatttagt gtagatatga taaaactatt gttttgttgg agaacttgat acgccgcgtt 126300ctctgtagtc gacgctctca aatgggaaac gatctccatt atttttttgg aatcggatac 126360aatatcttcg gtatcttgac gcagtctagt atacatagag ttaagagaga ttagagtttg 126420tacattaagc aacatgtctc taaatgtggc tacaaacttt tcctttttca catcatctag 126480tttattatat accgatttca caacggcacc agatttaagg

aaccagaatg aaaaactctg 126540ataactacaa tatttcatca tagttacgat tttatcatct tctatagttg gtgtaatagc 126600gcataccttt ttctccaaga ctggaaccaa cgtcataaaa atgtttaaat caaaatccat 126660atcaacatct gatgcgctaa gaccagtctc gcgttcaaga ttatctttac taatggtgac 126720gaactcatcg tatagaactc taagtttgtc cattatttat ttacagattt agttgtttaa 126780tttatttgtg ctcttccaga gttgggatag tatttttcta acgtcggtat tatattatta 126840ggatctacgt tcatatgtat cataatatta atcatccacg ttttgataaa tctatcttta 126900gcttctgaaa taacgtattt aaacaaagga gaaaaatatt tagctacggc atcagacgca 126960ataacatttt ttgtaaatgt aacgtattta gacgacagat cttcgttaaa aagttttcca 127020tctatgtaga atccatcggt tgttaacacc attcccgcgt cagattgaat aggagtttga 127080atagtttgtt ttggaaatag atccttcaat aacttatagt tgggtgggaa aaaatcgatt 127140ttatcactag actctttctt ttttactatc attacctcat gaactatttc ttgaatgagt 127200atatgtattt tctttcctat atcggacgcg ttcattggaa aatataccat gtcgttaact 127260ataagaatat ttttatcctc gtttacaaac tgaataatat cagatgtagt tcgtaaacga 127320actatatcat caccagcaca acatctaact atatgatatc cactagtttc ctttagtcgt 127380ttattatctt gttccatatt agcagtcatt ccatcattta agaaggcgtc aaaaataata 127440gggagaaatg acattttgga ttctgttaca actttaccaa aattaaggat atacggactt 127500actatctttt tctcaacgtc aatttgatga acacacgatg aaaatgtact tcgatgagat 127560tgatcatgta gaaaacaaca agggatacaa tatttccgca tatcatgaaa tatattaaga 127620aatcccacct tattatattt ccccaaagga tccatgcatg taaacattat gccgttatca 127680ttaataaaga cttctttctc atcggatctg taaaagttgt tactgatttt tttcattcca 127740ggatctagat aattaataat gatgggtttt ctattcttat tctttgtatt ttggcatatc 127800ctagaccagt aaacagtttc cactttggta aaatcagcag acttttgaac gctattaaac 127860atggcattaa tggcaataac taaaaatgta aaatattttt ctatgttagg aatatggttt 127920ttcactttaa tagatatatg gtttttggcc aaaatgatag atattttttt atccgaggat 127980agtaaaatat tattagtcgc cgtctctata aaaatgaagc tagtctcgat atccaatttt 128040attctagaat tgataggagt cgccaaatgt accttatacg ttatatctcc cttgatgcgt 128100tccatttgtg tatctatatc ggacacaaga tctgtaaata gttttacgtt attaatcatc 128160acggtatcgc cgtcgctaga taacgctaat gtaccatcca agtcccaaat ggagagattt 128220aactgttcat cgtttagaat aaaatgatta ccggtcatat taataaagtg ttcatcgtat 128280ctagataaca acgacttata attaatgtcc aagtcttgaa ctcgctgaat gatctttttt 128340aacccagtta gttttagatt ggtacgaaat atattgttaa actttgattc tacagtaatg 128400tccaaatcta gttgtggaaa tacttccatc aacattgttt caaacttgat aatattatta 128460tctacatctt cgtacgatcc aaattccgga atagatgtat cgcacgctct ggccacccag 128520ataaccaaaa agtcacacgc tccaggatat acattgtata aaaagctatc gttttttagt 128580agggtttttt tctgcgtgta tacgaaggga ttaaaaatag tattatcaac gtaactatat 128640tccaaattat tcttatgaga atagataata atatcgtcct taatatctaa caaatttcct 128700aaatatccct ttaattgagt cattcgaagc gtcaatagaa tatgtctctt aactatttcc 128760ggctgttgta tatttaaatg acttcgtaaa aaataatata tgggcgactt ctcatctatg 128820taatcatatg gagtgagata tagggctcgt tctacctcct gccccttacc cacctgtaat 128880accaattgcg gacttactat atatcgcata tttatatcgt ggggtaaagt gaaaatctac 128940taccgatgat gtaagtctta caatgttcga accagtacca gatcttaatt tggaggcctc 129000cgtagaacta ggggaggtaa atatagatca aacaacacct atgataaagg agaatagcgg 129060ttttatatcc cgtagtagac gtctattcgc ccatagatct aaggatgatg agagaaaact 129120agcactacga ttctttttac aaagacttta ttttttagat catagagaga ttcattattt 129180gttcagatgc gttgacgctg taaaagacgt cactattacc aaaaaaaata acattatcgt 129240ggcgccttat atagcacttt taactatcgc atcaaaagga tgcaaactta cagaaacaat 129300gattgaagca ttctttccag aactatataa tgaacatagt aagaaattta aattcaactc 129360tcaagtatcc atcatccaag aaaaactcgg ataccagttt ggaaactatc acgtttatga 129420ttttgaaccg tattactcta cagtagctct ggctattcga gatgaacatt catctggcat 129480ttttaatatc cgtcaagaga gttatctggt aagttcatta tctgaaataa catatagatt 129540ttatctaatt aatctaaaat ctgatcttgt tcaatggagt gctagtacgg gcgctgtaat 129600taatcaaatg gtaaatactg tattgattac agtgtatgaa aagttacaac tggtcataga 129660aaatgattca caatttacat gttcattggc tgtggaatca aaacttccaa taaaattact 129720taaagataga aatgaattat ttacaaaatt cattaacgag ttaaaaaaga ccagttcatt 129780caagataagc aaacgcgata aggatacgct actaaaatat tttacttagg actggagtta 129840gaatttatag acgactcatt tcgtttatca ttgttactat tattactatt actatcatta 129900ttagtgttgg cattattagt attcttcttg tcatcttgtt cagaaatata cagcaatgct 129960atacctaata ctaaatacat tatcatgctc gcaatggctc taacaacaac gaaccaaaat 130020gaatttggtc gtagcttttg ttcacaaaaa tacataaaga aatgtctaca taaatctatg 130080gcgccattgg ctacttgaaa tagcgccagt cctcctacag attttaatat agctgtataa 130140catgacattt attcatcatc aaaagagaca gagtcaccat ctgtcatatt tagatttttt 130200ttcatgtgtt caaagtatcc tctactcatt tcattataat agtttatcat acttagaatt 130260ttaggacgga tcaatgagta agacttgact agatcgtcag tagtaatttg tgcatcgtct 130320attctgcatc cgcttcgtcg aataatgtat agcatcgctt tgagattctc catagctatc 130380aagtctttat acaatgacat ggaaatatct gtgaatactt tatacttctc caacatcgat 130440gccttaacat catcgcctac tttagcattg aaaatacgtt ctattgtgta gatggatgta 130500gcaagatttt taaacaacaa tgccatctta cacgatgatt gcctcaagtc tccaatcgtt 130560tgtttagaac gattagctac agagtccaat gcttggctga ctagcatatt attatcttta 130620gaaattgtat tcttcaatga ggcgtttatc atatctgtga tttcgttagt catattacag 130680tctgactggg ttgtaatgtt atccaacata tcacctatgg atacggtaca cgtaccagca 130740tttgtaataa tcctatctaa gatgttgtat ggcattgcgc agaaaatatc ttctcctgta 130800atatctccac tctcgataaa tctactcaga ttattcttaa atgccttatt ctctggagaa 130860aagatatcag tgtccatcat ttcattaata gtatacgcag aaaagatacc acgagtatca 130920attctatcca agatacttat cggttccgag tcacagataa tggtttcctc tccttcggga 130980gatcctgcat agaaatatct aggacaatag tttctatact gtctgtaact ctgataatct 131040ctaaagtcac taactgatac catgaaattg agaagatcaa acgctgaagt aattaatttt 131100tctgcctcgt ttttactaca actagttttc atcaatgtag tgacgatgta ttgtttagtt 131160acttttggtc taatactgat gatagagata ttattgcttc ccataatgga tcttctagta 131220gtcaccttaa agcccattga tgcgaatagc agatagataa agtcttggta tgactccttt 131280ctaatatagt acggactacc tttgtcaccc aactttatac ccacataagc cataacaacc 131340tctttaatag ccgtttcatg aggtttatca gccatgagcc tgagtagttg gaagaatctc 131400atgaatcccg tctcagaaag tcctatatgc atgatagatt tatctttcct gggaaactct 131460cgtatagtca tagatgaaat actcttcaaa gtttctgaaa taagattagt aacagtctta 131520cctccgacta ctctaggtaa caaacaaact ctaataggtg ttttctctgc ggagataata 131580tcagaaagga tagagcaata agtagtatta ttgtgattat aaagaccgaa tacataacag 131640gtagaattta taaacatcat gtcctgaagg tttttagact tgtattcctc gtaatccata 131700ccgtcccaaa acatggattt ggtaactttg atagccgtag atctttgttc cttcgccaac 131760aggttaaaga aattaataaa gaatttgttg tttctattta tgtccacaaa ttgcacgttt 131820ggaagcgcca cggttacatt cactgcagca ttttgaggat cgcgagtatg aagtacgatg 131880ttattgttta ctggtatatc tggaaagaaa tctaccagtc taggaataag agattgatat 131940cgcatagaaa tagtaaagtt tataatctca tcatcgaaga gcattttgtt accattgtaa 132000taaatatcca ctctgtcata tgtataaatg aagtactgtt caaacatgat gagatgttta 132060tatgttggca tagtagtgag atcgacgttt ggtaatggca atgtattaag attaactcca 132120taatgtctag cagcatctgc gatgttataa gcgtcgtcaa agcggggtcg atcttgtatt 132180gttatatatt gtctaacacc tataagatta tcaaaatctt gtctgcttaa tacaccgtta 132240acaatttttg ccttgaattc ttttattggt gcattaataa catccttata gaggatgtta 132300aacaaataag tgttatcaaa gttaagatct ggatatttct tttctgctag aacatccatt 132360gagtcggagc catctggttt aatataacca ccgataaatc tagctctgta ttctgtatcc 132420gtcaatctaa tattaagaag gtgttgagtg aaaggtggaa gatcgtaaaa gctgtgagta 132480ttaatgatag gattagtttc cgaactaatg ttaattgggg tattaataat atctatattt 132540ccagcgttaa gtgtaacatt aaacagtttt aattcacgtg acgtggtatc aattaaataa 132600ttaatgccca atttggatat agcagcctga agctcatctt gtttagttac ggatcctaat 132660gagttattaa gcaatatatc gaacggatga acgaaggttg ttttgagttt gtcgcatact 132720ttgtaatcta gacatagatg cggaagaacg gtagaaacta tacgaaataa atattcagag 132780tcctctaatt gatcaagagt aactattgac ttaataggca tcatttattt agtattaaat 132840gacgaccgta ccagtgacgg atatacaaaa cgatttaatt acagagtttt cagaagataa 132900ttatccatct aacaaaaatt atgaaataac tcttcgtcaa atgtctattc taactcacgt 132960taacaacgtg gtagatagag aacataatgc cgccgtagtg tcatctccag aggaaatatc 133020ctcacaactt aatgaagatc tatttccaga tgatgattca ccggccacta ttatcgaacg 133080agtacaacct catactacta ttattgacga tactccacct cctacgtttc gtagagagtt 133140attaatatcg gaacaacgtc aacaacgaga aaaaagattt aatattacag tatcgaaaaa 133200tgctgaagca ataatggaat ctagatctat aataacttct atgccaacac aaacaccatc 133260cttgggagta gtttatgata aagataaaag aattcagatg ttagaggatg aagtggttaa 133320tcttagaaat caacgatcta atacaaaatc atctgataat ttagataatt ttaccaaaat 133380actatttggt aagactccgt ataaatcaac agaagttaat aagcgtatag ccatcgttaa 133440ttatgcaaat ttgaacgggt cccccttatc agtcgaggac ttggatgttt gttcggagga 133500tgaaatagat agaatctata aaacgattaa acaatatcac gaaagtagaa aacgaaaaat 133560tatcgtcact aacgtgatta ttattgtcat aaacattatc gagcaggcat tgctaaaact 133620cggatttgaa gaaatcaaag gactgagtac cgatatcact tcagaaatta tcgatgtgga 133680gatcggagat gactgcgatg ctgtagcatc aaaactagga atcggtaaca gtccggttct 133740taatattgta ttgtttatac tcaagatatt cgttaaacga attaaaatta tttaatttaa 133800tacattccca tatccagaca acaatcgtct ggattaatct gttcctgtcg tctcataccg 133860gacgacatat taatcttttt attagtgggc atctttttag atggtttctt tttcccagca 133920ttaactgatt cgatacctag aagatcgtga ttgatctctc cgaccattcc acgaacttct 133980aattggccgt ctctgacggt accataaact attttaccag cattagtaac agcttggaca 134040atctgaccat ccatcgcatt gtacgatgta gtagtaactg ttgttctacg tctaggagca 134100ccagaagtat ttttggagcc cttggaggct gatgtagaag aagacgagga ttttgatttt 134160ggtttacatg taatacattt tgaactcttt gattttgtat cacatgcgcc ggcagtcaca 134220tctgtttgag aattaagatt attgttgcct cctttgacgg ctgcatctcc accgatttgc 134280gctagtagat ttttaagctg tggtgtaatc ttattaactg tttcgatata atcatcgtaa 134340ctgcttctaa cggctaaatt ttttttatcc gccatttaga agctaaaaat atttttattt 134400atgcagaaga tttaactaga ttatacaatg aactaatatg atccttttcc agattattta 134460caaacttggt attttttggt tctggaggag gcgaatttaa attcggactt ggattcggat 134520tttgtaagtt cttgatctta ttatacatcg agtataggat ggcgacagta actgctacac 134580aaataccgat caaaagaaga ataccaatca tttattgaca ataacttcac tattgatcaa 134640gtatgcaata tatcatcttt tcactaaata agtagtaata atgattcaac aatgtcgaga 134700tatatggacg ataataattt agttcatgga aatatcgcta tgattggtgt gaatgactcc 134760gctaactctg tggggtgcgc agtgctttcc ccacatagaa taaattagca ttccgactgt 134820gataataata ccaagtataa acgccataat actcaatact ttccatgtac gagtgggact 134880agtagactta ctaaagtcaa taaaggcgaa gatacacgaa agaatcaaaa gaatgattcc 134940agcgattagc acgccggaaa aataatttcc aatcataagc atcatgtcca tttaactaat 135000aaaaatttta aatcgccgaa tgaacaaagt ggaatataaa ccatataaaa acaatagttt 135060gtactgcaaa aataatatct atttttgttt tcgaagatat ggtaaaatta aatagtagta 135120cacagcatgt tataactaac agcagcaacg gctcgtaatt acttatcatt tactagacga 135180aaaggtggtg ggatattttc ttgctcaaat aatacgaata tatcacccat ccattttatg 135240cgatgtttat atactctaat ctttaataga tctatagacg acgggtttac caacaatata 135300gattttatcg attcatctaa tttaaaccct tccttaaacg tgaatgatct attatctggc 135360ataacgatga ccctacctga tgaatcggac aatgtactgg gccatgtaga ataaattatc 135420aacgaattat cgtctacgaa catttatatc atttgtttta attttaggac gcgaataaat 135480ggatataaaa tagaaaataa cagatattac aaccagtgtt atggccgcgc ccaaccaggt 135540aggcagtttt attttatctt ttactacagg ttctcctgga tgtacgtcac caacggcgga 135600cgtagttcta gtacaattag acgtaagttc cgcttgggaa ttttttaacg ctaaagagtt 135660aacgttaatc gtgcacccaa cgtatttaca tctagttctt tgaacatctt gattataata 135720taaccatttt ctatctctag attcgtcagt gcactcatgt aaccaacata ccctaggtcc 135780taaatattta tctccggaat tagattttgg ataattcgcg caccaacaat ttctatttcc 135840tttatgatcg ttacaaaaga cgtataatgc cgtatcccca aaagtaaaat aatcaggacg 135900aataattcta ataaactcag aacaatatct cgcatccata tgtttggagc aaatatcgga 135960ataagtagac atagccggtt tccgttttgc acgtaaccat tctaaacaat tggggtttcc 136020aggatcgttt ctacaaaatc cagtcatgaa atcatcacaa tgttctgtct tgtaattatt 136080attaaatatt tttggacagt gtttggtatt tgtcttagaa caacattttg ccacgctatc 136140actatcgccc aggagataat ccttttttat aaaatgacat cgttgcccgg atgctatata 136200atcagtggcg tgttttaaat ccttaatata ttcaggagtt acctcgttct gataatagat 136260taatgatcca ggacgaaatt tgaaagaact acatggttct ccatgaatta atacatattg 136320tttagcaaat tcaggaacta taaaactact acaatgatct atcgacatac catctatcaa 136380acaaaacttg ggtttaattt ctcccggaga tgtttcataa tagtacgtat aactttcttc 136440tgcaaactta acagctctat tatattcagg ataattaaaa cctaattcca tatatttgtc 136500tcgtatatct gctattcctg gtgctatttt gattctatta agagtaacag ctgcccccat 136560tcttaataat cgtcagtatt taaactgtta aatgttggta tatcaacatc taccttattt 136620cccgcagtat aaggtttgtt gcaggtatac tgttcaggaa tggttacatt tatacttctt 136680ctatagtcct gtctttcgat gttcatcaca tatgcaaaga acagaataaa caaaataatg 136740taagaaataa tattaaatat ctgtgaattc gtaaatacat tgattgccat aataattaca 136800gcagctacaa tacacacaat agacattccc acagtgttgc cattacctcc acgatacatt 136860tgagttacta agcaataggt aataactaag ctagtaagag gcaatagaaa agatgagata 136920aatatcatca atatagagat tagaggaggg ctatatagag ccaagacgaa caaaatcaaa 136980ccgagtaacg ttctaacatc attatttttg aagattccca aataatcatt cattcctcca 137040taatcgtttt gcatcatacc tccatcttta ggcataaacg attgctgctg ttcctctgta 137100aataaatctt tatcaagcac tccagcaccc gcagagaagt cgtcaagcat attgtaatat 137160cttaaataac tcatttatat attaaaaaat gtcactatta aagatggagt ataatcttta 137220tgccgaacta aaaaaaatga cttgtggtca acccctaagt ctttttaacg aagacgggga 137280tttcgtagaa gttgaaccgg gatcatcctt taagtttctg atacctaagg gattttacgc 137340ctctccttcc gtaaagacga gtctagtatt cgagacatta acaacgaccg ataataaaat 137400cactagtatc aatccaacaa atgcgccaaa gttatatcct cttcaacgca aagtcgtatc 137460tgaagtagtt tctaatatga ggaaaatgat cgaatcaaaa cgtcctctat acattactct 137520tcacttggcg tgtggatttg gtaagactat taccacgtgt tatcttatgg ctacacacgg 137580tagaaaaacc gtcatttgcg tacccaataa aatgttaata catcaatgga agacacaggt 137640agaggcagtc ggattggaac ataagatatc catagatgga gtaagtagtc tattaaagga 137700actaaagact caaagtccgg atgtattaat agtagtcagt agacatctga caaacgatgc 137760cttttgtaaa tatatcaata agcattatga tttgttcatc ttggatgaat cacatacgta 137820taatctgatg aacaatacag cagttacaag atttttagcg tattatcctc cgatgatgtg 137880ttatttttta actgctacac ctagaccagc taacagaatt tattgtaaca gtattattaa 137940tattgccaag ttatccgatc taaaaaaaac tatctatgcg gtagatagtt tttttgagcc 138000atattccaca gacaatatta gacatatgat aaaacgatta gatggaccat ctaataaata 138060tcatatatat actgagaagt tattatctgt agacgagcct agaaatcaac ttattcttga 138120taccctggta gaagaattca agtcaggaac tattaatcgc attttagtta ttactaaact 138180acgtgaacat atggtattat tctacaaacg attattagat cttttcggac cagaggttgt 138240atttatagga gacgcccaaa atagacgtac tccagatatg gtcaaatcaa tcaaggaact 138300aaatagattt atattcgtat ccaccttatt ttattccggt actggtttag atattcctag 138360tttggattcg ttgttcattt gctcggcagt aatcaacaat atgcaaatag agcaattact 138420agggagggta tgtcgagaaa cagaactatt agataggacg gtatatgtat ttcctaacac 138480atccatcaaa gaaataaagt acatgatagg aaatttcatg caacgaatta ttagtctgtc 138540tgtagataaa ctaggattta aacaaaaaag ttatcggaaa catcaagaat ccgatcccac 138600ttttgtatgt acaacatcct ccagagaaga acgtgtatta aatagaatat ttaactcgca 138660aaatcgttaa gaagtttaag cgacgatccg catgctgcac aggccagtgt attacccctc 138720atagtattaa tataatccaa tgatactttt gtgatgtcgg aaatcttaac caatttagac 138780tgacaggcag aacacgtcat gcaatcatca tcgtcatcga taactgtagt cttgggcttc 138840tttttgcggc tcttcattcc ggaacgcaca ttggtgctat ccatttaggt agtaaaaaat 138900aagtcagaat atgccctata acacgatcgt gcaaaacctg gtatatcgtc tctatcttta 138960tcacaatata gtgtatcaac atctttatta ttattgacct cgtttatctt ggaacatgga 139020atgggaacat ttttgttatc aacggccacc tttgccttaa ttccagatgt tgtaaaatta 139080taactaaaca gtctatcatc gacacaaatg aaattcttgt ttagacgttt gtagtttacg 139140tatgcggctc gttcgcgtct cattttttca gatattgcag gtactataat attaaaaata 139200agaatgaaat aacataggat taaaaataaa gttatcatga cttctagcgc tgatttaact 139260aacttaaaag aattacttag tctgtacaaa agtttgagat tttcagattc tgcggctata 139320gaaaagtata attctttggt agaatgggga acatctactt actggaaaat aggcgtgcaa 139380aaggtagcta atgtcgagac gtcaatatct gattattatg atgaggtaaa aaataaaccg 139440tttaatattg atccgggcta ttacattttc ttaccggtat attttgggag cgtctttatt 139500tattcgaagg gtaaaaatat ggtagaactt ggatctggaa actcttttca aataccagat 139560gatatgcgaa gtgcgtgtaa caaagtatta gacagcgata acggaataga ctttctgaga 139620tttgttttgt taaacaatag atggataatg gaagatgcta tatcaaaata tcagtctcca 139680gttaatatat ttaaactagc tagtgagtac ggattaaaca tacccaaata tttagaaatt 139740gaaatagagg aagacacatt atttgacgac gagttatact ctattataga acgctctttc 139800gatgataaat ttccaaaaat atccatatcg tatattaagt tgggagaact tagacggcaa 139860gttgtagact ttttcaaatt ctcattcatg tatattgagt ccatcaaggt agatcgtata 139920ggagataata tttttattcc tagcgttata acaaaatcag gaaaaaagat attagtaaaa 139980gatgtagacc atttaatacg atctaaggtt agagaacata catttgtaaa agtaaaaaag 140040aaaaacacat tttccatttt atacgactat gatggaaacg gaacagaaac tagaggagaa 140100gtaataaaac gaattataga cactatagga cgagactatt atgttaacgg aaagtatttc 140160tctaaggttg gtagtgcagg cttaaagcaa ttgactaata aattagatat taatgagtgc 140220gcaactgtcg atgagttagt tgatgagatt aataaatccg gaactgtaaa acgaaaaata 140280aaaaaccaat cagcatttga tttaagcaga gaatgtttgg gatatccaga agcggatttt 140340ataacgttag ttaataacat gcggttcaaa atagaaaatt gtaaggttgt aaatttcaat 140400attgaaaata ctaattgttt aaataacccg agtattgaaa ctatatatgg aaactttaac 140460cagttcgtct caatctttaa tgtcgtcacc gatgtcaaaa aaagattatt cgagtgaaat 140520aatatgcgcc tttgatatag gtgcaaaaaa tcctgccaga actgttttag aagtcaagga 140580taactccgtt agggtattgg atatatcaaa attagactgg agttctgatt gggaaaggcg 140640catagctaaa gatttgtcac aatatgaata cactacagtt cttctagaac gtcagcctag 140700aaggtcgccg tatgttaaat ttatctattt tattaaaggc tttttatatc atacatcggc 140760tgccaaagtt atttgcgtct cgcctgtcat gtctggtaat tcatatagag atcgaaaaaa 140820gagatcggtc gaagcatttc ttgattggat ggacacattc ggattgcgag actccgttcc 140880ggatagacgc aaattagacg atgtagcgga tagtttcaat ttggctatga gatacgtatt 140940agataaatgg aatactaatt atacacctta taataggtgt aaatctagaa attacataaa 141000aaaaatgtaa taacgttagt aacgccatta tggataatct atttaccttt ctacatgaaa 141060tagaagatag atatgccaga actattttta actttcatct aataagttgc gatgaaatag 141120gagatatata tggtcttatg aaagaacgca tttcctcaga ggatatgttt gataatatag 141180tgtataataa agatatacat cctgccatta agaaactagt gtattgcgac atccaactta 141240ctaaacacat tattaatcag aatacgtatc cggtatttaa cgattcttca caagtgaaat 141300gttgtcatta tttcgacata aactcagata atagcaatat tagctctcgt acagtagaga 141360tatttgagag ggaaaagtca tctcttgtat catatattaa aactaccaat aagaagagaa 141420aggtcaatta cggcgaaata aagaaaactg ttcatggagg cactaatgca aattactttt 141480ccggtaaaaa gtctgacgag tatctgagta ctacagttag atccaacatt aatcaacctt 141540ggatcaaaac catttctaag agaatgagag tagatatcat

taatcactct atagtaacgc 141600gtggaaaaag ctctatatta caaactatag aaattatttt tactaataga acatgtgtga 141660aaatattcaa ggattctact atgcacatta ttctatccaa ggacaaggat gaaaaggggt 141720gtatacacat gattgacaaa ttattctatg tctattataa tttatttctg ttgttcgaag 141780atatcatcca aaacgagtac tttaaagaag tagctaatgt tgtaaaccac gtactcacgg 141840ctacggcatt agatgagaaa ttattcctaa ttaagaaaat ggctgaacac gatgtttatg 141900gagttagcaa tttcaaaata gggatgttta acctgacatt tattaagtcg ttggatcata 141960ccgttttccc ctctctgtta gatgaggata gcaaaataaa gttttttaag gggaaaaagc 142020tcaatattgt agcattacga tctctggagg attgtataaa ttacgtgact aaatccgaga 142080atatgataga aatgatgaag gaaagatcga ctattttaaa tagcatagat atagaaacgg 142140aatcggtaga tcgtctaaaa gaattgcttc taaaatgaaa aaaaacactg attcagaaat 142200ggatcaacga ctcggatata agtttttggt gcctgatcct aaagccggag ttttttatag 142260accgttacat ttccaatatg tatcgtattc taattttata ttgcatcgat tgcatgaaat 142320cttgaccgtc aagcggccac tcttatcgtt taagaataat acagaacgaa ttatgataga 142380aattagcaat gttaaagtga ctcctccaga ttactcacct ataatcgcga gtattaaagg 142440taagagttat gacgcattag ccacgttcac tgtaaatatc tttaaagagg taatgaccaa 142500agagggtata tccatcacta aaataagtag ttatgaggga aaagattctc atttgataaa 142560aattccgcta ctaataggat acgggaataa aaatccactt gatacagcca agtatcttgt 142620tcctaatgtc ataggtggag tctttatcaa taaacaatct gtcgaaaaag taggaattaa 142680tctagtagaa aagattacaa catggccaaa atttagggtt gttaagccaa actcattcac 142740tttctcgttt tcctccgtat cccctcctaa tgtattaccg acaagatatc gccattacaa 142800gatatctctg gatatatcac aattggaagc gttgaatata tcatcgacaa agacatttat 142860aacggtcaat attgttttgc tgtctcaata tttatctaga gtgagtctag aattcattag 142920acgtagttta tcatacgata tgcctccaga agttgtctat ctagtaaacg cgataataga 142980tagtgctaaa cgaattactg aatctattac tgactttaat attgatacat acattaatga 143040cctggtggaa gctgaacaca ttaaacaaaa atctcagtta acgatcaacg agttcaaata 143100tgaaatgctg cataactttt tacctcatat gaactataca cccgatcaac taaagggatt 143160ttatatgata tctttactaa gaaagtttct ctactgtatc ttccacactt ctagatatcc 143220agatagagat tcgatggttt gtcatcgcat cctaacgtac ggcaaatatt ttgagacgtt 143280ggcacatgat gaattagaga attacatagg caacatccga aacgatatca tgaacaatca 143340caagaacaga ggcacttacg cggtaaacat tcatgtacta acaactcccg gacttaatca 143400tgcattttct agtctattga gtggaaagtt caaaaagtca gacggtagtt atcgaacaca 143460tcctcactat tcatggatgc agaatatttc tattcctagg agtgttggat tttatccgga 143520tcaagtaaag atttcaaaga tgttttctgt cagaaaatac catccaagtc aatatcttta 143580cttttgttca tcagacgttc cggaaagagg tcctcaggta ggtttagtat ctcaattgtc 143640tgtcttgagt tccattacaa atatactaac gtctgagtat ttggatttgg aaaagaaaat 143700ttgtgagtat atcagatcat attataaaga tgatataagt tactttgaaa caggatttcc 143760aatcactata gaaaatgctc tagtcgcatc tcttaatcca aatatgatat gtgattttgt 143820aactgacttt agacgtagaa aacggatggg attcttcggt aacttggagg taggtattac 143880tttagttagg gatcacatga atgaaattcg cattaatatt ggagcgggaa gattagtcag 143940accattcttg gttgtggata acggagagct catgatggat gtgtgtccgg agttagaaag 144000cagattagac gacatgacat tctctgacat tcagaaagag tttccgcatg tcatcgaaat 144060ggtagatata gaacaattta cttttagtaa cgtatgtgaa tcggttcaaa aatttagaat 144120gatgtcaaag gatgaaagaa agcaatacga tttatgtgac tttcctgccg aatttagaga 144180tggatatgtg gcatcttcat tagtgggaat caatcacaat tctggaccca gagctattct 144240tggatgtgct caagctaaac aagctatctc ttgtctgagt tcggatatac gaaataaaat 144300agacaatgga attcatttga tgtatccaga gaggccaatc gtgattagta aggctttaga 144360aacttcaaag attgcggcta attgcttcgg ccaacatgtt actatagcat taatgtcgta 144420caaaggtatc aatcaagagg atggaattat cattaaaaaa caatttattc agagaggcgg 144480tctcgatatt gttacagcca agaaacatca agtagaaatt ccgttggaaa actttaataa 144540caaagaaaga gataggtcta acgcctattc aaaattagaa agtaatggat tagttagact 144600gaatgctttc ttggaatccg gagacgctat ggcacgaaat atctcatcaa gaactcttga 144660agatgatttt gctagagata atcagattag cttcgatgtt tccgagaaat ataccgatat 144720gtacaaatct cgcgttgaac gagtacaagt agaacttact gacaaagtta aggtacgagt 144780attaaccatg aaagaaagaa gacccattct aggagacaaa tttaccacta gaacgagtca 144840aaagggaaca gtcgcgtatg tcgcggatga aacggaactt ccatacgacg aaaatggtat 144900cacaccagat gtcattatta attctacatc catcttctct agaaaaacta tatctatgtt 144960gatagaagtt attttaacag ccgcatattc tgctaagccg tacaacaata agggagaaaa 145020ccgacctgtc tgttttccta gtagtaacga aacatccatc gatacatata tgcaattcgc 145080taaacaatgt tatgagcatt caaatccgaa attgtccgat gaagaattat cggataaaat 145140cttttgtgaa aagattctct atgatcctga aacggataag ccttatgcat ccaaagtatt 145200ttttggacca atttattact tgcgtctgag gcatttaact caggacaagg caaccgttag 145260atgtagaggt aaaaagacga agctcattag acaggcgaat gagggacgaa aacgtggagg 145320aggtatcaag ttcggagaaa tggagagaga ctgtttaata gcgcatggtg cagccaatac 145380tattacagaa gttttgaaag attcggaaga agattatcaa gatgtgtatg tttgtgaaaa 145440ttgtggagac atagcagcac aaatcaaggg tattaataca tgtcttagat gttcaaaact 145500taatctctct cctctcttaa caaaaattga taccacacac gtatctaaag tatttcttac 145560tcaaatgaac gccagaggcg taaaagtcaa attagatttc gaacgaagac ctccttcgtt 145620ttataaacca ttagataaag ttgatctcaa gccgtctttt ctggtgtaat attctagttt 145680ggtagtagat acatatcaat atcatcaaat tcgagatccg aattataaaa tgggcgtgga 145740ttgttaacta tagaatcgga cgtctgatat tcgaaaatct gtggagtttc aggttttggt 145800ggaggtgtaa ctgctacttg ggatactgaa gtctgatatt cagaaagctg tggatgttct 145860ggttcggcat ccaccgatgg tgttacacca ctactaattg gttcagtaac gtctgtggac 145920gatggaggca ccacttctac agaacctgta gcctcagtca tcaacggagc tacttcaatg 145980cgaggaaatg tataatttgg taatggtttc tcatgtggat ctgaagaaga ggtaagatat 146040ctactagaaa gataccgatc acgttctagt tctcttttgt agaacttaac tttttctttc 146100tccgcatcta gttgatattc caacctcttc acgttactac gttcagattc caattcacgt 146160tcgcatgggt tacctccaca gtttttacga gcgatttcac gttcagcctt catgcgtctc 146220tccctctctc tatcgagttt atcagagcag tctttctgaa ggcgatcgaa ctccataaat 146280ttctccaacg ctttgattgt ttccatagat ttccgaagtt cagcttttag gactgtgatt 146340ctttttcttt cgaattcaca gctggatgta caaccgtttc cattaccgcc atctctaagt 146400ttcttttcta gatcggcaac atttcatccc catgcctttt acattcctcg agtctactgt 146460cgtcgaaata tcgttccagc tccttttcga catcaataac tttagcacgt tgtctctcaa 146520gctctctttt gtagttatct gattccctgg cacgtttaag atcttcatgc aattgagtca 146580gctcttaact tcctctcttg cttcttcgtc atagtactta caatcactat gggatccatt 146640gttaccacgt ctacactcgg cgagctcgcg tttaagagat tcaatttccc gtttgtattg 146700gtccatgttt ccattgctac caccattaga tttacaggct gctagttgtc gttcgagatc 146760agaaatacgg gttttcttgg aattgatttc gtcgatgtac ttggcatcga aacacttatt 146820aagttctttt tccaattcta cgattttatt tctttcgcga gtcaattccc tcctgtagta 146880actatctgtt ttgtcagatt cacgctctct acgtagactt tcttgcaagt tactaatttg 146940ttccctagca cgtccgagtt tagttttata tgctgaatag agttctgatt catcctttga 147000gcagatctct agcgatcgtt taagattcct gattctagtc tttagcctat ttacctcctc 147060agaagatgtt ccgttaccgt tgcgtttaca ctcgttaagc tgtctatcaa gatccatgat 147120tctatctcta aaacgttgca tctctctttc catatcagca ttgctttcat tattacgtct 147180gcagtcactc aactgtcttt caatatctga gattctatct ctaagacgtc gcatctctct 147240ctgtttcggc attggtttca ttattacgtc tacagtcgtt caactgtctt tcaagatctg 147300atattctaga ttggagtctg ctaatctctg tagcattttc acggcattca ctcagttgtc 147360tttcaagatc tgaaatttta gattggagtc tgctaatctc tgtaagattt cctcctccgc 147420tctcgatgca gtcggtcaac ttattctcta gttctctaat acgcgaacgc agtgcatcaa 147480cttcttgcgt gtcttcctgg ttgcgtgtac attcatcgag tctagattcg agatctctaa 147540cgcgtcgtcg ttcttcctca agttctctgc gtactacaga aagcgtgtcc ttatcttgtt 147600gatatttagc aatttctgat tctagagtac tgattttgct tacgtagtta ctaatagttg 147660tcttggcctt atcaagatcc tccttgtatt tgtcgcattc cttgatatcc ctacgaagtc 147720tggacagttc ccattcgaca ttacgacgtt tatcgatttc agctcggaga tcgtcatcgc 147780gttgttttag ccacatacga ctgagttcaa gttctcgttg acaagatcca tctacttttc 147840cattcctaat agtatccagt tccttttcta gttctgaacg catttcttgt tccctatcaa 147900gcgattctct caattctcgg atagtcttct tatcaatttc taataaatct gaaccatcat 147960ctgtcccatt ttgaatatcc ctgtgttctt tgatctcttt tgtaagtcgg tcgattcttt 148020cggttttata aacagaatcc ctttccaaag tcctaatctt actgagttta tcactaagtt 148080ctgcattcaa ttcggtgagt tttctcttgg cttcttccaa ctctgtttta aactctccac 148140tattttcgca ttcttcctcg catttatcta accattcaat tagtttatta ataactagtt 148200ggtaatcagc gattcctata gccgttcttg taattgtggg aacataatta ggatcttcta 148260atggattgta tggcttgata gcatcatctt tatcattatt agggggatgg acaaccttaa 148320ttggttggtc ctcatctcct ccagtagcgt gtggttcttc aataccagtg ttagtaatag 148380gcttaggcaa atgcttgtcg tacgcgggca cttcctcatc catcaagtat ttataatcgg 148440gttctacttc agaatattct tttctaagag acgcgacttc gggagttagt agaagaactc 148500tgtttctgta tctatcaacg ctggaatcaa tactcaagtt aaggatagcg aatacctcat 148560cgtcatcatc cgtatcctct gaaacgccat catatgacat ttcatgaagt ctaacgtatt 148620gataaataga atcagattta gtattaaaca gatccttaac ctttttagta aacgcatatg 148680tatattttag atctccagat ttcataatat gatcacatgc cttaaatgtc agtgcttcca 148740tgatataatc tggaacacta atgggtgacg aaaaagatac agcaccatat gctacgttga 148800taaataaatc tgaaccacta agtagataat gattaatgtt aaggaaaaga aaatattcag 148860tgtataggta tgtcttggcg tcatatcttg tactaaacac gctaaacagt ttgttaatgt 148920gatcaatttc caatagatta attagagcag cgggaatacc aacaaacata ttaccacatc 148980cgtattttct atgaatatca catatcatgt taaaaaatct tgatagaaga gcgaatatct 149040cgtctgactt aatgagtcgt agttcagcag caacataagt cataactgta aatagaacat 149100actttcctgt agtgttgatt ctagactcca catcaacacc attattaaaa atagttttat 149160atacatcttt aatctgctct ccgttaatcg tcgaacgttc tagtatacgg aaacactttg 149220atttcttatc tgtagttaat gacttagtga tatcacgaag aatattacga attacatttc 149280ttgtttttct tgagagacct gattcagaac tcaactcatc gttccatagt ttttctacct 149340cagtggcgaa atctttggag tgcttggtac atttttcaat aaggttcgtg acctccattt 149400attataaaaa atttattcaa aacttaacta caatcgggta attataagat cgtagatctc 149460ccatgtggcg gaatactacc atctatcgca tgtggatgga cagtaggtaa tggccatggg 149520aacagtaatg attgcatatt tatctttctt gctagtatta ctgcatattg tcccaatgtt 149580tcgatgtgat gttctaacct atcaactgcc gctgtatcac aacaatagtg tccgatgaaa 149640ttaagattat gatccaatgt gtttaatata tgattatcaa gtcttatacg atccgcgtct 149700tttttgacag gatcaggttc ttctacagga agaagtttcg gcctcttatg atattcatgt 149760ctgggaaacg gtggtctagg gtgaggctcc ggtatcggag tgggttttgg attataatca 149820tcatcgtcta tgacatcatc atcatcttcg acttcgatat ttattttgct atcttgatga 149880tgtcctgtat cagttgcatt ttcagcactc gactgaatat tagcgcattc attgtctatt 149940attaccatat ttctaaaccc aaaatgtatg tgttgaacat cagtactatc gttgatgagt 150000cttatagcat gaattcgctt atcgttatcg ggtttatctt ctgtcacctt agcaattcct 150060tttttattaa actctacata atcatatcca tttctattgt ttgttctaat ataaacgagt 150120atagcatcat tgctaaattt ttcaatagta tcgaaaacag aatatcctaa accatataat 150180atatattcag gaacactcaa actaaatgtc caggattctc ctaaatacgt aaactttaat 150240agtgcgaaat cattcaaaaa tctaccactt atagatagat agtacataaa tgcgtatagt 150300agtctaccta tctctttatt atgaaaaccg gcattacgat catatatgtc gtgatatacc 150360tgtgatccgt ttacgttaaa ccataaatac atgggtgatc ctataaacat gaatttattt 150420ctaattctca gagctatagt taattgaccg tgtaatattt gcttacatgc atacttgata 150480cgcttattaa taagattttt atcattgctc gttatctcag aatcgtatat ataaggagta 150540ccattgtgat tcttaccaga tattatacaa aatactatat ataaaatata ttgacccacg 150600ttagtaatca tataaatgtt taacgtttta aattttgtat ttaatgatcc attatcatac 150660gctagcatgg tcttatgata ttcattcttt aaaatataat attgtgttag ccattgcatt 150720ggggctccta atggagattt tttattctca tccattttag gataggcttt cataaagtcc 150780ctaataactt cgtgaataat gtttctatgt tttctactga tgcatgtatt tgcttcgatt 150840tttttatccc atgtttcatc tatcatagat ttaaacgcag taatgctcgc aacattaaca 150900tcttgaaccg ttggtacaat tccgttccat aaatttataa tgttcgccat ttatataact 150960cattttttga atatactttt aattaacaaa agagttaagt tactcatatg gacgccgtcc 151020agtctgaaca tcaatctttt tagccagaga tatcatagcc gctcttagag tttcagcgtg 151080attttccaac ctaaatagaa cttcatcgtt gcgtttacaa cacttttcta tttgttcaaa 151140ctttgttgtt acattagtaa tctttttttc caaattagtt agccgttgtt tgagagtttc 151200ctcattgtcg tctccatcgg ctttaacaat tgcttcgcgt ttagcctctg gctttttagc 151260agcctttgta gaaaaaaatt cagttgctgg aattgcaaga tcgtcatctc cggggaaaag 151320agttccgtcc atttaaagta cagattttag aaactgacac tctgcgttat ttatatttgg 151380tacaacacat ggattataaa tatcgatgtt aataacatca gaaaatgtaa agtctataca 151440ttgttgcatc gtgttaaatt ttctaatgga tctagtatta ttgggtccaa cttctgcctg 151500aaatccaaat atggaagcgg atacaaaacc gtttcctgga taaaccacac atctccactt 151560ttgctttaca tcagaaattg tgtcgttgac atcttgaact ctcctatcta atgccggtgt 151620tccacctata gattttgaat attcgaatgc tgcatgagta gcattaaatt ccttaatatt 151680gccataattt tcatatattg agtaaccctg gataaaaagt aaacacaccg cagccgtcgc 151740taccacaata aaaaaaattg atagagagtt catttataat ctattagaag ctgacaaaat 151800ttttttacac gcatcagaca atgctttaat aaatagttca acatctactt ttgtcatatc 151860gaaccgatgg tatgattcta acctagaatt acatccgaaa aagttgacta tgttcatagt 151920cattaagtca ttaacaaaca acattccaga ctctggatta taagacgata ctgtttcgtc 151980acaattacct accttaatca tgtgattatg aatattggct attagagcac cttctaagaa 152040atctataata tctttgaaac acgatttaaa atcaaaccac gaatatactt ctacgaagaa 152100agttagttta cccataggag aaataactat aaatggagat ctaaatacaa aatccggatc 152160tatgatagtt ttaacattat tatattctct attaaatacc tccacatcta aaaatgttaa 152220ttttgaaact atgtcttcgt ttattaccgt acctgaacta aacgctataa gctctattgt 152280ttgagaactc tttaaacgat attcttgaaa tacatgtaac aaagtttcct ttaactcggt 152340cggtttatct accatagtta cagaatttgt atccttatct ataatataat aatcaaaatc 152400gtataaagtt atataattat cgcgttcaga ttgggatctt ttcaaataga ctaaaaaccc 152460catttctcta gtaagtatct tatgtatatg tttgtaaaat atcttcatgg tgggaatatg 152520ctctaccgca gttagccatt cctcattgac agcggtagat gtattagaca aaactattcc 152580aatgtttaac aagggccatt ttacgagatt attaaatcct tgtttgataa atgtagccaa 152640tgagggttcg agttcaacga cgattgaatt ctcttcccgc ggatgctgca tgatgaacga 152700cgggatgttg ttcgattgat ttggaattct ttttcgactt tttgtttata ttaaatattt 152760taaaatttat agcggatagc aattcatgta ccacggataa tgtagacgcg tattgcgcat 152820cgatatcttt attattagat aaatttatca ataaatgtga gaagtttgcc tcgttaaggt 152880cttccattta aatattatat aaacatttgt gtttgtaact tattcgtctt ttatggaata 152940gttttttact agtaaagctg caattacaca ctttgtccgt aaaacataaa tataaacacc 153000agcttttatc aatcgttcca aaaagtcgac ggcggacatt tttaacatgg catctatttt 153060aaatacactt aggtttttgg aaaaaacatc attttataat tgtaacgatt caataactaa 153120agaaaagatt aagattaaac ataagggaat gtcatttgta ttttataagc caaagcattc 153180taccgttgtt aaatacttgt ctggaggagg tatatatcat gatgatttgg ttgtattggg 153240gaaggtaaca attaatgatc taaagatgat gctattttac atggatttat catatcatgg 153300agtgacaagt agtggagcaa tttacaaatt gggatcgtct atcgatagac tttctctaaa 153360taggactatt gttacaaaag ttaataataa ttataattat gatgatacat tttttgacga 153420cgatgattga tcgctattgc acaattttgt ttttttactt tctaatatag cgtttagatt 153480ctttttcatg tgcgaatatt gatttactaa aatatctatg tttaactttt gttctataac 153540gtccttatcg gcggtatcgg tacatatacg taattcacct tcacaaaata cggagtcttc 153600gataataata gccaatcgat tattggatct agctgtctgt atcatattca acatgtttaa 153660tatatccttt cgtttcccct ttacaggcat cgatcgtagc atattttccg cgtctgatat 153720ggaaatgtta aaactacaaa aatgcgtaat gttagcccgt cctaatattg gtacgtgtct 153780ataagtttgg catagtagaa taatagacgt gtttaaatgc cttccgaagt ttaagaattc 153840tattagagta ttgcattttg atagtttatc acctacatca tcaaaaataa gtaaaaagtg 153900tgctgatttt ttatgatttt gtgcgacagc aatacatttt tctatgttac ttttagttcg 153960tatcagatta tattctagag attcctgact actaacgaaa ttaatatgat ttggccaaat 154020gtatccatca taatctgggt tataaacggg tgtaaacaag aatatatgtt tatatttttt 154080aactagtgta gaaaacagag atagtaaata gatagttttt ccagatccag atcctcccgt 154140taaaaccatt ctaaacggca tttttaataa attttctctt gaaaattgtt tttcttggaa 154200acaattcata attatattta cagttactaa attaatttga taataaatca aaatatggaa 154260aactaaggtt gttagtaggg aggagaacaa agaaggcaca tcgtgatata aataacattt 154320attatcatga tgacaccaga aaacgacgaa gagcagacat ctgtgttctc cgctactgtt 154380tacggagaca aaattcaggg aaagaataaa cgcaaacgcg tgattggtct atgtattaga 154440atatctatgg ttatttcact actatctatg attaccatgt ccgcgtttct catagtgcgc 154500ctaaatcaat gcatgtctgc taacgaggct gctattactg acgccgctgt tgccgttgct 154560gctgcatcat ctactcatag aaaggttgcg tctagcacta cgcaatatga tcacaaagaa 154620agctgtaatg gtttatatta ccagggttct tgttatatat tacattcaga ctaccagtta 154680ttctcggatg ctaaagcaaa ttgcactgcg gaatcatcaa cactacccaa taaatccgat 154740gtcttgacta cctggctcat tgattatgtt gaggatacat ggggatctga tggtaatcca 154800attacaaaaa ctacatccaa ttatcaagat tctgatgtat cacaagaagt tagaaagtat 154860ttttgtgtta aaacaatgaa ctaatattta tttttgtaca ttaataaatg aaatcgctta 154920atagacaaac tgtaagtagg tttaagaagt tgtcggtgcc ggccgctata atgatgatac 154980tctcaaccat tattagtggc ataggaacat ttctgcatta caaagaagaa ctgatgccta 155040gtgcttgcgc caatggatgg atacaatacg ataaacattg ttatttagat actaacatta 155100aaatgtctac agataatgcg gtttatcagt gtcgtaaatt acgagctaga ttgcctagac 155160ctgatactag acatctgaga gtattgttta gtatttttta taaagattat tgggtaagtt 155220taaaaaagac caataataaa tggttagata ttaataatga taaagatata gatattagta 155280aattaacaaa ttttaaacaa ctaaacagta cgacggatgc tgaagcgtgt tatatataca 155340agtctggaaa actggttaaa acagtatgta aaagtactca atctgtacta tgtgttaaaa 155400aattctacaa gtgacaacaa aaaatgaatt aataataagt cgttaacgta cgccgccatg 155460gacgccgcgt ttgttattac tccaatgggt gtgttgacta taacagatac attgtatgat 155520gatctcgata tctcaatcat ggactttata ggaccataca ttataggtaa cataaaaact 155580gtccaaatag atgtacggga tataaaatat tccgacatgc aaaaatgcta ctttagctat 155640aagggtaaaa tagttcctca ggattctaat gatttggcta gattcaacat ttatagcatt 155700tgtgccgcat acagatcaaa aaataccatc atcatagcat gcgactatga tatcatgtta 155760gatatagaag ataaacatca gccattttat ctattcccat ctattgatgt ttttaacgct 155820acaatcatag aagcgtataa cctgtataca gctggagatt atcatctaat catcaatcct 155880tcagataatc tgaaaatgaa attgtcgttt aattcttcat tctgcatatc agacggcaat 155940ggatggatca taattgatgg gaaatgcaat agtaattttt tatcataaaa gttgtaaagt 156000aaataataaa acaataaata ttgaactagt agtacgtata ttgagcaatc agaaatgatg 156060ctggtacctc ttatcacggt gaccgtagtt gcgggaacaa tattagtatg ttatatatta 156120tatatttgta ggaaaaagat acgtactgtc tataatgaca ataaaattat catgacaaaa 156180ttaaaaaaga taaagagttc taattccagc aaatctagta aatcaactga tagcgaatca 156240gactgggagg atcactgtag tgctatggaa caaaacaatg acgtagataa tatttctagg 156300aatgagatat tggacgatga tagcttcgct ggtagtttaa tatgggataa cgaatccaat 156360gttatagcgc ctagcacaga acacatttac gatagtgttg ctggaagcac gctgctaata 156420aataatgatc gtaatgaaca gactatttat cagaacacta cagtagtaat taatgaaacg 156480gagactgtta aagtacttaa tgaagatacc aaacagaatc ctaactattc atccaatcct 156540ttcgtaaatt ataataaaac cagtatttgt agcaagtcaa atccgtttat tacagaactt 156600aacaataaat ttagtgagaa taatccgttt agacgagcac

atagcgatga ttatcttaat 156660aagcaagaac aagatcatga acacgatgat atagaatcat cggtcgtatc attggtgtga 156720ttagtttcct ttttataaaa ttgaagtaat atttagtatt attgctgccg tcacgttgta 156780caaatggaga tattccctgt attcggcatt tctaaaatta gcaattttat tgctaataat 156840gactgtagat attatataga tacagaacat caaaaaatta tatctgatga gatcaataga 156900cagatggatg aaacggtact tcttaccaac atcttaagcg tagaagttgt aaatgacaat 156960gagatgtacc atcttattcc tcatagatta tcgacgatta tactctgtat tagttctgtc 157020ggaggatgtg ttatctctat agataatgac atcaatgaca aaaatattct aacatttccc 157080attgatcatg ctgtaatcat atccccactg agtaaatgtg tcgtagttag caagggtcct 157140acaaccatat tggttgttaa agcggatata cctagcaaac gattggtaac atcgtttaca 157200aacgacatac tatatgtaaa caatctgtca ctgattaatt atttgccgtt gtctgtattc 157260attattagac gagtcaccga ctatttggat agacgcatat gcgatcagat atttgctaat 157320aataagtggt attccattat aaccatcgac gataagcaat atcctattcc atcaaactgt 157380ataggtatgt cctctgccaa gtacataaat tctagcatcg agcaagatac tttaatccat 157440gtttgtaacc tcgagcatcc gttcgactca gtatacaaaa aaatgcagtc gtacaattct 157500ctacctatca aggaacaaat attgtacggt agaattgata atataaatat gagcattagt 157560atttctgtgg attaatagat ttctagtatg gggatcatta atcatctcta atctctaaat 157620acctcataaa acgaaaaaaa agctattatc aaatactgta cggaatggat tcattctctt 157680ctctttttat gaaactctgt tgtatatcta ctgataaaac tggaagcaaa aaatctgata 157740aaaagaataa gaataagatc aaggattata tggaacacga ttattataaa ataacaatag 157800ttcctggttc ctcttccacg tctactagct cgtggtatta tacacatgcc tagtaatagt 157860ctctttgcgt tgacggaaag cagactagaa ataacaggct aaaatgttca gacaccataa 157920tagttcccaa cccagataat aacagagttc catcaacaca ttcctttaaa ctcaatccca 157980aacccaaaac cgttaaaatg tatccggcca attgatagta gataatgagg tgtacagcgc 158040atgataattt acacagtaac caaaatgaaa atactttagt aattataaga aatatagatg 158100gtaacgtcat catcaacaat ccgataatat gcctgagagt aaacattgat ggataaaaca 158160aaaatgctcc gcataactct atcatggcaa taacacaacc aaacacttgt aaaattccta 158220aattagtaga aaatacaacg gatatcgatg tataagtgat ctcgagaaat aataagaata 158280aagtaatgcc cgtaaagata aacatcaaca ttgtttggta atcattaaac caattagtat 158340gaagttgaac taatttcaca gtagatttta ttccagtgtt atcctcgcat gtataagtac 158400ctggtaagat atctttatat tccataatca atgagacatc actatccgat aacgaatgaa 158460gtctagcact agtatgccat ttacttaata ttgtcgtctt ggaagtttta ttataagtta 158520aaatatcatg gttatccaat ttccatctaa tatactttgt cggattatct atagtacacg 158580gaataatgat ggtatcatta catgctgtat actctatggt ctttgtagtt gttataacaa 158640ccaacgtata gaggtatatc aacgatattc taactcttga cattttttat ttatttaaaa 158700tgataccttt gttatttatt ttattctatt ttgctaacgg tattgaatgg cataagtttg 158760aaacgagtga agaaataatt tctacttact tattagacga cgtattatac acgggtgtta 158820atggggcggt atacacattt tcaaataata aactaaacaa aactggttta actaataata 158880attatataac aacatctata aaagtagagg atgcggataa ggatacatta gtatgcggaa 158940ccaataacgg aaatcccaaa tgttggaaaa tagacggttc agacgaccca aaacatagag 159000gtagaggata cgctccttat caaaatagca aagtaacgat aatcagtcac aacggatgtg 159060tactatctga cataaacata tcaaaagaag gaattaaacg atggagaaga tttgacggac 159120catgtggtta tgatttatac acggcggata acgtaattcc aaaagatggt ttacgaggag 159180cattcgtcga taaagacggt acttatgaca aagtttacat tcttttcact gatactatcg 159240gctcaaagag aattgtcaaa attccgtata tagcacaaat gtgcctaaac gacgaaggtg 159300gtccatcatc attgtctagt catagatggt cgacgtttct caaagtcgaa ttagaatgtg 159360atatcgacgg aagaagttat agacaaatta ttcattctag aactataaaa acagataatg 159420atacgatact atatgtattc ttcgatagtc cttattccaa gtccgcatta tgtacctatt 159480ctatgaatac cattaaacaa tctttttcta cgtcaaaatt ggaaggatat acaaagcaat 159540tgccgtctcc agctcctggt atatgtttac cagctggaaa agttgttcca cataccacgt 159600ttgaagtcat agaaaaatat aatgtactag atgatattat aaagccttta tctaaccaac 159660ctatcttcga aggaccgtct ggtgttaaat ggttcgatat aaaggagaag gaaaatgaac 159720atcgggaata tagaatatac ttcataaaag aaaattctat atattcgttc gatacaaaat 159780ctaaacaaac tcgtagctcg caagtcgatg cgcgactatt ttcagtaatg gtaacttcga 159840aaccgttatt tatagcagat atagggatag gagtaggaat gccacaaatg aaaaaaatac 159900ttaaaatgta atcttaatcg agtacaccac acgacaatga acaaacataa gacagattat 159960gctggttatg cttgctgcgt aatatgcggt ctaattgtcg gaattatttt tacagcgaca 160020ctattaaaag ttgtagaacg taaattagtt catacaccat caatagataa aacgataaaa 160080gatgcatata ttagagaaga ttgtcctact gactggataa gctataataa taaatgtatc 160140catttatcta ctgatcgaaa aacctgggag gaaggacgta atgcatgcaa agctctaaat 160200ccaaattcgg atctaattaa gatagagact ccaaacgagt taagtttttt aagaagcatt 160260agacgcggat attgggtagg agaatccgaa atattaaacc agacaacccc atataatttt 160320atagctaaga atgccacgaa gaatggaact aaaaaacgga aatatatttg tagcacaacg 160380aatactccca aactgcattc gtgttacact atataacaat tacactacat ttttatcata 160440ccactacttc ggttagatgt tttagaaaaa aataaatatc gccgtaccgt tcttgttttt 160500ataaaaataa caattaacaa ttatcaaatt ttttctttaa tattttacgt ggttgaccat 160560tcttggtggt aaaataatct cttagtgttg gaatggaatg ctgtttaatg tttccacact 160620catcgtatat tttgacgtat gcagtcacat cgtttacgca atagtcagac tgtagttcta 160680tcatgcttcc tacatcagaa ggaggaacag ttttaaagtc tcttggtttt aatctattac 160740cgttagtttt catgaaatcc tttgttttat ccacttcaca ttttaaataa atgtccacta 160800tacattcttt tgttaatttt actagatcgt catgggtcat agaatttata ggttccgtag 160860tccatggatc caaactagca aacttcgcgt atacggtatc gcgattagtg tatacaccaa 160920ctgtatgaaa attaagaaaa cagtttaata gatcaacaga aatatttaat cctccgtttg 160980atacagatgc gccatattta tggatttcgg attcacacgt tgtttgtctg aggtgttcgt 161040ctagtgttgc ttctacgtaa acttcgattc ccatatattc tttattgtca gaatcgcata 161100ccgatttatc atcatacact gtttgaaaac taaatggtat acacatcaaa ataacaaata 161160ctaacgagta cattctgcaa tattgttatc gtaattggaa aaatagtgtt cgagtgagtt 161220ggattatgtg agtattggat tgtatatttt attttatatt ttgtaataag aataaaatgc 161280taatgtcaag tttattccaa tagatgtctt attaaaaaca tatataataa ataacaatgg 161340ctgaatggca taaaattatc gaggatatct caaaaaataa taagttcgag gatgccgcca 161400tcgttgatta caagactaca aagaatgttc tagctgctat tcctaacaga acatttgcca 161460agattaatcc gggtgaaatt attcctctca tcactaatcg taatattcta aaacctctta 161520ttggtcagaa atattgtatt gtatatacta actctctaat ggatgagaac acgtatgcta 161580tggagttgct tactgggtac gcccctgtat ctccgatcgt tatagcgaga actcataccg 161640cacttatatt tttgatgggt aagccaacaa catccagacg tgacgtgtat agaacgtgta 161700gagatcacgc tacccgtgta cgtgcaactg gtaattaaaa taaaaagtaa tattcatatg 161760tagtgtcaat tttaaatgat gatgatgaaa tgtataatat ccatattgac gatgtcaata 161820atgccggtat tggcatacag ttcatcgatt tttagatttc attcagagga tgtggaatta 161880tgttatgggc atttgtattt tgataggatc tataatgtag taaatataaa atataatccg 161940catattccat atagatataa ttttattaat cgcacgttaa ccgtagatga actagacgat 162000aatgtctttt ttacacatgg ttatttttta aaacacaaat atggttcact taatcctagt 162060ttgattgtct cattatcagg aaacttaaaa tataatgata tacaatgctc agtaaatgta 162120tcgtgtctca ttaaaaattt ggcaacgagt acatctacta tattaacatc taaacataag 162180acttattctc tacatcggtc cacgtgtatt actataatag gatacgattc tattatatgg 162240tataaagata taaatgacaa gtataatgac atctatgatt ttactgcaat atgtatgcta 162300atagcgtcta cattgatagt gaccatatac gtgtttaaaa aaataaaaat gaactcttaa 162360ttatgctatg ctattagaaa tggataaaat caaaattacg gttgattcaa aaattggtaa 162420tgttgttacc atatcgtata acttggaaaa gataactatt gatgtcacac ctaaaaagaa 162480aaaagaaaag gatgtattat tagcgcaatc agttgctgtc gaagaggcaa aagatgtcaa 162540ggtagaagaa aaaaatatta tcgatattga agatgacgat gatatggatg tagaaagcgc 162600gtaatactat ctataaaaat aagtatataa taaatacttt ttatttacgg tactcttgta 162660gtggtgatac cctactcaat tattttttta aaaaaatact tattctgatt cttctaacca 162720tttccgtgtt cgttcgaatg ccacatcgac gtcaaagata ggggagtagt tgaaatctag 162780ttctgcattg ttggtacgca cctcaaatgt agtgttggat atcttcaacg tatagttgtt 162840gagtagtgat ggttttctaa atagaattct cttcatatca ttcttgcacg cgtacatttt 162900tagcatccat cttggaattc tagatccttg ttctattccc aatggtttca tcaataaaag 162960attaaacata tcgtacgaac acgatggaga gtaatcgtag caaaagtaag catttccttt 163020aatctcagat cccggatact ggatatattt tgcagccaac acgtgcatcc atgcaacatt 163080tcctacatat acccggctat gcaccgcgtc atcatcgact gtacgataca taatgttacc 163140gtgttgctta cattgctcgt aaaagacttt cgtcaatttg tctccttctc cgtaaattct 163200agtgggtctt aggcaacaag tatacaattt tgctccattc atgattacgg aattattggc 163260tttcataacc agttgctcgg ccatacgttt actttttgcg tatacatgtc ctggtgatat 163320atcataaagg gtatgctcat ggccgatgaa tggatcaccg tgtttattgg gtcctattgc 163380ttccatgcta ctagtataga tcaaatactt gattcctagg tccacacaag ctgccaaaat 163440agtctgtgtt ccataatagt ttactttcat gatttcatta tcggtgtatt ttccaaatac 163500atccactaga gcagccgtat gaataatcag atttacccca tctagcgctt ctctcacctt 163560atcaaagtcg tttatatcac attgtatata gtttataacc ttaactttcg aggttattgg 163620ttgtggatct tctacaatat ctatgactct gatttcttga acatcatctg cactaattaa 163680cagttttact atatacctgc ctagaaatcc ggcaccacca gtaaccgcgt acacggccat 163740tgctgccact cataatatca gactacttat tctattttac taaataatgg ctgtttgtat 163800aatagaccac gataatatca gaggagttat ttactttgaa ccagtccatg gaaaagataa 163860agttttagga tcagttattg gattaaaatc cggaacgtat agtttaataa ttcatcgtta 163920cggagatatt agtcaaggat gtgattccat aggcagtcca gaaatattta tcggtaacat 163980ctttgtaaac agatatggtg tagcatatgt ttatttagat acagatgtaa atatatctac 164040aattattgga aaggcgttat ctatttcaaa aaatgatcag agattagcgt gtggagttat 164100tggtatttct tacataaatg aaaagataat acattttctt acaattaacg agaatggcgt 164160ttgatatatc agttaatgcg tctaaaacaa taaatgcatt agtttacttt tctactcagc 164220aaaataaatt agtcatacgt aatgaagtta atgatacaca ctacactgtc gaatttgata 164280gggacaaagt agttgacacg tttatttcat ataataaaca taatgacacc atagagataa 164340gaggggtgct tccagaggaa actaatattg gttgcgcggt taatacgccg gttagtatga 164400cttacttgta taataagtat agttttaaac tgattttagc agaatatata agacacagaa 164460atactatatc cagcaatatt tattcggcat tgatgacact agatgatttg gctattaaac 164520agtatggaga cattgatcta ttatttaatg agaaacttaa agtagactcc gattcgggac 164580tatttgactt tgtcaacttt gtaaaggata tgatatgttg tgattctaga atagtagtag 164640ctctatctag tctagtatct aaacattggg aattgacaaa taaaaagtat aggtgtatgg 164700cattagccga acatatatct gatagtattc caatatctga gctatctaga ctacgataca 164760atctatgtaa gtatctacgc gggcacactg agagcataga ggatgaattt gattattttg 164820aagacgatga ttcgtctaca tgttctgccg taaccgacag ggaaacggat gtataatttt 164880ttttatagcg tgaaggatat gataaaaaat ataattgttg tatttatccc attccaatca 164940ccttatatga ttctgtaaca caataaagga gtctcataga tgtatagagg tcagatactg 165000gtttgataaa ctgtttattc cacataagta tgtttgactt tatggttaga cccgcatact 165060ttaacaaatc actgaaaatt ggagttaggt attgacctct cagaatcagt tgccgttctg 165120gaacattaaa tgtatttttt atgatatact ccaacgcatt tatgtgggca tacaacaagt 165180cattactaat ggagtattcc aagagtttta gttgtctagt atttaacaag agaagagatt 165240tcaacagact gtttatgaac tcgaatgccg cctcattgtc gcttatattg atgatgtcga 165300attctcccaa tatcatcacc gatgagtagc tcatcttgtt atcgggatcc aagttttcta 165360aagatgtcat taaaccctcg atcatgaatg gatttatcat catcgttttt atgttggaca 165420tgagcttagt ccgtttgtcc acatctatag acgacgattt ctgaattatt tcatatatcc 165480ctctctttaa ctccaggaac ttgtcaggat ggtctacttt aatatgttct cgtctaagag 165540atgaaaatct ttggatggtc gcatgtgact tttctctaaa ggatgacgtt gcccaagatc 165600ctctcttaaa tgaatccatc ttatccttgg acaagatgga cagtctattt tccttagatg 165660gtttaatatt tttgttaccc atgatctata aaggtagacc taatcgtctc ggatgaccta 165720tatatttatt ttcagtttta ttatacgcat aaattgtaaa aaatatgtta ggtttacaaa 165780aatgtctcgt ggggcattaa tcgtttttga aggattggac aaatctggaa aaacaacaca 165840atgtatgaac atcatggaat caatactttc aaacacaata aaatacctta actttcctca 165900gagatccact gtcactggaa agatgataga tgactatcta actcgtaaaa aaacctataa 165960tgatcatata gttaatctat tattttgtgc aaatagatgg gagtttgcat cttttataca 166020agaacaacta gaacagggaa ttactttaat agttgataga tacgcatttt ctggagtagc 166080gtatgccgcc gctaaaggcg cgtcaatgac tctcagtaag agttatgaat ctggattgcc 166140taaacccgac ttagttatat tcttggaatc tggtagcaaa gaaattaata gaaacgtcgg 166200cgaggaaatt tatgaagatg ttacattcca acaaaaggta ttacaagaat ataaaaaaat 166260gattgaagaa ggagatattc attggcaaat tatttcttct gaattcgagg aagatgtaaa 166320gaaggagttg attaagaata tagttataga ggctatacac acggttactg gaccagtggg 166380gcaactgtgg atgtaatagt gaaattacat tttttataaa tagatgttag tacagtgtta 166440taaatggatg aagcatatta ctctggcaac ttggaatcag tactcggata cgtgtccgat 166500atgcataccg aactcgcatc aatatctcaa ttagttattg ccaagataga aactatagat 166560aatgatatat taaacaagga cattgtaaat tttatcatgt gtagatcaaa cttggataat 166620ccatttatct ctttcctaga tactgtatat actattatag atcaagagaa ctatcagact 166680gagttgatta attcattaga cgacaatgaa attatcgatt gtatagttaa taagtttatg 166740agcttttata aggataacct agaaaatata gtagatgcta tcattactct aaaatatata 166800atgaataatc cagattttaa aactacgtat gccgaagtac tcggttccag aatagccgat 166860atagatatta aacaagtgat acgtaagaat atactacaat tgtctaatga tatccgcgaa 166920cgatatttgt gaaaaatatt aaaaaaaaat acttttttta ttaaatgacg tcgcttcgcg 166980aatttagaaa attatgctgt gatatatatc acgcatcagg atataaagaa aaatctaaat 167040taattagaga ctttataaca gatagggatg ataaatattt gatcattaag ctattgcttc 167100ccggattaga cgatagaatt tataacatga acgataaaca aattataaaa ttatatagta 167160taatatttaa acaatctcag gaagatatgc tacaagattt aggatacgga tatataggag 167220acactattag gactttcttc aaagagaaca cagaaatccg tccacgagat aaaagcattt 167280taactttaga agaagtggat agtttcttaa ctacgttatc atccgtaact aaagaattgc 167340atcaaataaa attattgact gatatcgcat ccgtttgtac atgtaatgat ttaaaatgtg 167400tagtcatgct tattgataaa gatctaaaaa ttaaagcggg tcctcggtac gtacttaacg 167460ctattagtcc tcatgcctat gatgtgttta gaaaatctaa taacttgaaa gagataatag 167520aaaattcatc taaacaaaat ctagactcta tatctatttc tgttatgact ccaattaatc 167580ccatgttagc ggaatcgtgt gattctgtca ataaagcgtt taaaaaattt ccatcaggaa 167640tgtttgcgga agtcaaatac gatggtgaaa gagtacaagt tcataaaaat aataacgagt 167700ttgccttctt tagtagaaac atgaaaccag tactctctca taaagtggat tatctcaaag 167760aatacatacc gaaagcattt aaaaaagcta cgtctatcgt attggattct gaaattgttc 167820ttgtagacga acataatgta ccgctaccgt ttggaagttt aggaatacac aaaaagaaag 167880aatataaaaa ctctaacatg tgtttgttcg tgtttgactg tttgtacttt gatggattcg 167940atatgacgga cattccattg tacgaacgaa gatcttttct caaagatgtt atggttgaaa 168000tacccaatag aatagtattc tcagagttga cgaatattag taacgagtct cagttaactg 168060acgtattgga tgatgcacta acgagaaaat tagaaggatt ggtcttaaaa gatattaatg 168120gagtatacga accgggaaag agaagatggt taaaaataaa gcgagactat ttgaacgagg 168180gttccatggc agattctgcc gatttagtag tactaggtgc ttactatggt aaaggagcaa 168240agggtggtat catggcagtc tttctaatgg gttgttacga cgatgaatcc ggtaaatgga 168300agacggttac caagtgttca ggacacgatg ataatacgtt aagggagttg caagaccaat 168360taaagatgat taaaattaac aaggatccca aaaaaattcc agagtggtta gtagttaata 168420aaatctatat tcccgatttt gtagtagagg atccgaaaca atctcagata tgggaaattt 168480caggagcaga gtttacatct tccaagtccc ataccgcaaa tggaatatcc attagatttc 168540ctagatttac taggataaga gaggataaaa cgtggaaaga atctactcat ctaaacgatt 168600tagtaaactt gactaaatct taatagttac atacaaacta aaaattaaaa taacactatt 168660tagttggtgg tcgccatgga tggtgttatt gtatactgtc taaacgcgct agtaaaacat 168720ggcgaggaaa taaatcatat aaaaaatgat ttcatgatta aaccatgttg tgaaagagtt 168780tgtgaaaaag tcaagaacgt tcacatcggc ggacaatcta aaaacaatac agtgattgca 168840gatttgccat atctggataa tgctgtatcc gatgtatgca aatcgatata tatatagtat 168900caagaatatc cagatttgct aatttgataa agatagatga cgatgacaag actcctactg 168960gtgtatataa ttattttaaa cttaaagatg ccattcctgt tattatatct ataggaaagg 169020ataaagatgt ctgtgaacta ttaatctcat cagacatatc gtgtgcatgc gtggagttaa 169080attcatatca cgtagccatt cttcccatgg atgtttcctt ttttaccaaa ggaaatgcat 169140cattgattat tctcctgttt gatttctcta tcgatgcggc acctctctta agaagtgtaa 169200ccgataataa tgttattata tctagacacc agcgtctaca tgacgagctt ccgagttcca 169260attggttcaa gttttacata agtataaagt ccgactattg ttctatatta tatatggttg 169320ttgatggatc tgtgatgcat gcgatagctg ataatagaac tcacgcaatt attagcaaaa 169380atatattaga caatactacg attaacgatg agtgtagatg ctgttatttt gaaccacaga 169440ttaggattct tgatagagat gagatgctca atggatcatc gtgtgatatg aacagacatt 169500gtattatgat gaatttacct gatgtaggcg aatttggatc tagtatgttg gggaaatatg 169560aacctgacat gattaagatt gctctttcgg tggctggtaa tttaataaga aatcgagact 169620acattcccgg gagacgagga tatagctact acgtttacgg tatagcctct agataatttt 169680tttaagcacg aaataaaaaa cataatttta aaccaatcta tttcatacta ttttgtgtga 169740tcaccatgga cataaagata gatattagta tttctggtga taaatttacg gtgactacta 169800ggagggaaaa tgaagaaaga aaaaaatatc tacctctcca aaaagaaaaa actactgatg 169860ttatcaaacc tgattatctt gagtacgatg acttgttaga tagagatgag atgtttacta 169920ttctagagga atattttatg tacagaggtc tattaggcct cagaataaaa tatggacgac 169980tctttaacga aattaaaaaa ttcgacaatg atgcggaaga acaattcggt actatagaag 170040aactcaagca gaaacttaga ttaaattctg aagagggagc agataacttt atagattata 170100taaaggtaca aaaacaggat atcgtcaaac ttactgtata cgattgcata tctatgatag 170160gattgtgtgc atgcgtggta gatgtttgga gaaatgagaa actgttttct agatggaaat 170220attgtttacg agcgattaaa ctgtttattg atgatcacat gcttgataag ataaaatcta 170280tactgcagaa tagactagtg tatgtggaaa tgtcatagaa agttaatgag agcaaaaata 170340tataaggttg tattccatat ttgttatttt tttctgtaat agttagaaaa atacattcga 170400tggtctatct atcagattat tatgtgttat aaggtacttt ttctcataat aaactagagt 170460atgagtaaga tagtgttttt caaaacatat aaatctaaaa ttgatggatg agatatacag 170520ctattaattt cgaaaatata ttttaatctg ataactttaa acatggattt ttgatggtgg 170580tttaacgttt taaaaaaaga ttttgttatt gtagtatatg ataatattaa aagatggata 170640taaagaattt gctgactgta tgtactattt tttacattac tacattggct acggcagata 170700tacctactcc gccaccaacg gggcatgtga cgagggagaa tatcttgata agaggcataa 170760tcaatgttgt aatcggtgtc cacctggaga atttgccaag gtcagatgta gtggtagtga 170820taacacaaaa tgtgaacgct gcccacctca tacatatacc gcaatcccca attactctaa 170880tggatgtcat caatgtagaa aatgcccaac aggatcattt gataaggtaa agtgtaccgg 170940aacacagaac agtaaatgtt cgtgtcttcc tggttggtat tgcgctactg attcttcaca 171000gactgaagat tgtcgagatt gtataccaaa aaggagatgt ccatgcggat actttggtgg 171060aatagatgaa caaggaaatc ctatttgtaa atcgtgttgt gttggtgaat attgcgacta 171120cctacgtaat tatagacttg atccatttcc tccatgcaaa ctatctaaat gtaattaatt 171180atgattttga tgataatgtt accatacatt atatcgctac ttggttagtg tattattcag 171240tatgaagacc tattaataat tacttatctt ttgacgatct tgttataatt ataatataaa 171300aacttatggc atagtaactt ataattgctg acgcgataaa ttcgtaataa tctgttttgt 171360tcaaaggaat ctacaggcat aaaaataaaa atataattta taatatactc ttacagcgcg 171420ccatcatgaa taacagcagt gaattgattg ctgttattaa tggatttaga aatagtggac 171480gattttgtga tattagtata gttattaatg atgaaaggat aaacgctcat aaactcatcc 171540tatctggagc ctccgaatat ttttccattc tgttttccaa taattttatc gattctaatg 171600aatacgaagt taatctaagt catttagatt atcaaagtgt taacgatttg atcgattata 171660tttatgggat acctttgagc ctaactaacg ataacgtgaa

atatattctt tcaaccgctg 171720attttttaca aattggatct gccattactg agtgcgaaaa atacatactt aaaaatcttt 171780gttctagaaa ctgtatcgat ttctacatat acgctgataa atataataac aagaaaatag 171840aatcagcgtc gtttaacaca atattacaaa atattttgag actcatcaac gatgaaaact 171900ttaaatactt aacagaggaa tcaatgataa aaattttaag cgatgatatg ttaaatataa 171960aaaatgagga tttcgcccca ctaattctca ttaaatggtt agagagtact caacaatcat 172020gcaccgtcga gttacttaga tgcctcagaa tatcattgct ttccccacaa gttataaaat 172080cactttatag tcatcgactg gttagttcaa tctacgaatg tataacattc ttaaacaata 172140tagcattctt ggatgaatca tttcctagat accatagcat cgagttgata tctatcggta 172200taagtaattc gcatgataag atttccataa actgctacaa tcataaaaaa aatacatggg 172260aaatgatatc ttcacgtaga tataggtgta gtttcgcagt ggccgtcctg gataatatta 172320tttatatgat gggtggatat gatcagtccc cgtatagaag ttcaaaggtt atagcgtaca 172380atacatgtac aaattcttgg atatatgata taccagagct aaaatatcct cgttctaatt 172440gtgggggact ggctgatgac gaatacattt attgtatagg cggcatacgc gatcaggatt 172500catcgttgac atctagtatt gatagatgga agccatcaaa accatattgg cagaagtatg 172560ctaaaatgcg cgaaccaaaa tgtgatatgg gggttgcgat gttaaacgga ttaatatatg 172620tcatgggtgg aatcgttaaa ggtgacacgt gtaccgacgc actagagagt ttatcagaag 172680atggatggat gaagcatcaa cgtcttccaa taaaaatgtc caatatgtcg acgattgttc 172740atgatggcaa gatttatata tctggaggtt acaacaatag tagtgtagtt aatgtaatat 172800cgaatctagt ccttagctat aattcgatat atgatgaatg gaccaaatta tcatcattaa 172860acattcctag aattaatccc gctctatggt cagcgcataa taaattatat gtaggaggag 172920gaatatctga tgatgttcga actaatacat ctgagacata cgacaaagaa aaagattgtt 172980ggacattgga taatggtcac gtgttaccac gcaattatat aatgtataaa tgcgaaccga 173040ttaaacataa atatccattg gaaaaaacac agtacacgaa tgattttcta aagtatttgg 173100aaagttttat aggtagttga tagaacaaaa tacataattt tgtaaaaata aatcactttt 173160tatactaata tgacacgatt accaatactt ttgttactaa tatcattagt atacgctaca 173220ccttctcctc agacatctaa aaaaataggt gatgatgcaa ctctatcatg taatcgaaat 173280aatacaaatg actacgttgt tatgagtgct tggtataagg agcccaattc cattattctt 173340ttagctgcta aaagcgacgt cttgtatttt gataattata ccaaggataa aatatcttac 173400gactctccat acgatgatct agttacaact atcacaatta aatcattgac tgctagagat 173460gccggtactt atgtatgtgc attctttatg acatcgccta caaatgacac tgataaagta 173520gattatgaag aatactccac agagttgatt gtaaatacag atagtgaatc gactatagac 173580ataatactat ctggatctac acattcaccg gaaactagtt ctgagaaacc tgattatata 173640gataattcta attgctcgtc ggtattcgaa atcgcgactc cggaaccaat tactgataat 173700gtagaagatc atacagacac cgtcacatac actagtgata gcattaatac agtaagtgca 173760tcatctggag aatccacaac agacgagact ccggaaccaa ttactgataa agaagaagat 173820catacagtca cagacactgt ctcatacact acagtaagta catcatctgg aattgtcact 173880actaaatcaa ccaccgatga tacgtacaat gataatgata cagtaccacc aactactgta 173940ggcggtagta caacctctat tagcaattat aaaaccaagg actttgtaga aatatttggt 174000attaccgcat taattatatt gtcggccgtg gcaatattct gtattacgta ttatatatgt 174060aataaacgtt cacgtaaata caaaacagag aacaaagtct agatttttga cttacataaa 174120tgtctgggat agtaaaatct atcatattga gcggaccatc tggtttagga aagacagcca 174180tagccaaaag actatgggaa tatatttgga tttgtggtgt cccataccac tagatttcct 174240cgtcctatgg aacgagaagg tgtcgattac cattacgtta acagagaggc catctggaag 174300ggaatagccg ccggaaactt tctagaacat actgagtttt taggaaatat ttacggaact 174360tctaaaactg ctgtgaatac agcggctatt aataatcgta tttgtgtgat ggatctaaac 174420atcgatggcg ttagaagtct taaaaatacg tacctaatgc cttactcggt gtatataaga 174480cctacctctc ttaaaatggt tgagaccaag cttcgtcgta gaaacactga agcggatgat 174540gagattcatc gtcgtgtgat gttggcaaaa actgacatgg atgaggcagg tgaagccggt 174600ctattcgaca ctattattat tgaagatgat gtgaatttag catatagtaa gttaattcag 174660atactacagg accgtattag aatgtatttt aacactaatt agagacttaa gacttaaaac 174720ttgataatta ataatataac tcgtttttat atgtgtctat ttcaacgtct aatgtattag 174780ttaaatatta aaacttacca cgtaaaactt aaaatttaaa atgatatttc attgacagat 174840agatcacaca ttatgaactt tcaaggactt gtgttaactg acaattgcaa aaatcaatgg 174900gtcgttggac cattaatagg aaaaggtgga ttcggtagta tttatactac taatgacaat 174960aattatgtag taaaaataga gcccaaagct aacggatcat tatttaccga acaggcattt 175020tatactagag tacttaaacc atccgttatc gaagaatgga aaaaatctca caatataaag 175080cacgtaggtc ttatcacgtg caaggcattt ggtctataca aatccattaa tgtggaatat 175140cgattcttgg taattaatag attaggtgca gatctagatg cggtgatcag agccaataat 175200aatagattac caaaaaggtc ggtgatgttg atcggaatcg aaatcttaaa taccatacaa 175260tttatgcacg agcaaggata ttctcacgga gatattaaag cgagtaatat agtcttggat 175320caaatagata agaataaatt atatctagtg gattacggat tggtttctaa attcatgtct 175380aatggcgaac atgttccatt tataagaaat ccaaataaaa tggataacgg tactctagaa 175440tttacaccta tagattcgca taaaggatac gttgtatcta gacgtggaga tctagaaaca 175500cttggatatt gtatgattag atggttggga ggtatcttgc catggactaa gatatctgaa 175560acaaagaatt gtgcattagt aagtgccaca aaacagaaat atgttaacaa tactgcgact 175620ttgttaatga ccagtttgca atatgaacct agagaattgc tgcaatatat taccatggta 175680aactctttga catattttga ggaacccaat tacgacaagt ttcggcacat attaatgcag 175740ggtgtatatt attaagtgtg gtgtttggtc gatgtaaaat ttttgtcgat aaaaattaaa 175800aaataactta atttattatt gatctcgtgt gtacaaccga aatcatggcg atgttttacg 175860cacacgctct cggtgggtac gacgagaatc ttcatgcctt tcctggaata tcatcgactg 175920ttgccaatga tgtcaggaaa tattctgttg tgttagttta taataacaag tatgacattg 175980taaaagacaa atatatgtgg tgttacagtc aggtgaacaa gagatatatt ggagcactgc 176040tgcctatgtt tgagtgcaat gaatatctac aaattggaga tccgatccat gatcaagaag 176100gaaatcaaat ctctatcatc acatatcgcc acaaaaacta ctatgctcta agcggaatcg 176160ggtacgagag tctagacttg tgtttggaag gagtagggat tcatcatcac gtacttgaaa 176220caggaaacgc tgtatatgga aaagttcaac atgattattc tactatcaaa gagaaggcca 176280aagaaatgag tacacttagt ccaggaccta tcatcgatta ccacgtctgg ataggagatt 176340gtatctgtca agttactgct gtggacgtac atggaaagga aattatgaga atgagattca 176400aaaagggtgc ggtgcttccg atcccaaatc tggtaaaagt taaacttggg gagaatgata 176460cagaaaatct ttcttctact atatcggcgg caccatcgag gtaaccacct ctctggaaga 176520cagcgtgaat aatgtactca tgaaacgttt ggaaactata cgccatatgt ggtctgtcgt 176580atatgatcat tttgatattg tgaatggtaa agaatgctgt tatgtgcata cgcatttgtc 176640taatcaaaat cctataccga gtactgtaaa aacaaatttg tacatgaaga ctatgggatc 176700atgcattcaa atggattcca tggaatctct agagtatctt agcgaactga aggaatcagg 176760tggatggagt cccagaccag aaatgcagga atttgaatat ccagatggag tggaagacac 176820tgaatcaatt gagagattgg tagaggagtt cttcaataga tcagaacttc aggctggtga 176880atcagtcaaa tttggtaatt ctattaattg ttaaacatac atctgtttca gctaagcaac 176940taagaacacg tatacggcag cagcttcctt tatactctca tcttttacca acacaaaggg 177000tggatatttg ttcattggag ttgataataa tacacacaaa gtatttggat tcacggtggg 177060ttacgactac ctcagactga tagagaatga tatagaaaag catatcaaaa gactttgtgt 177120tgtgtatttc tgtgagaaga aagaggacat caagtacgcg tgtcgattca tcaaggtata 177180taaacctggg gatgagacta ccttgacata cgtgtgcgct atcaaagtgg aaagatgctg 177240ttgtgctgtg tttgcagatt ggccagaatc atggtatatg gatactaatg gtatcaagaa 177300gtattctcca gatgaatggg tgtcacatat aaaattttaa ttaatgtaat agagaacaaa 177360taataaggtt gtaatatcat atagacaata actaacaatt aattagtaac tgttatctct 177420tttttaacta accaactaac tatataccta ttaatacatc gtaattatag ttcttaacat 177480ctattaatca ttaattcgct tctttaattt tttataaact aacattgtta attgaaaagg 177540gataacatgt tacagaatat aaattatata tggatttttt taaaaaggaa atacttgact 177600ggagtatata tttatctctt cattatatag cacgcgtgtt ttccaatttt tccacatccc 177660atataataca ggattataat ctcgttcgaa catacgagaa agtggataaa acaatagttg 177720attttttatc taggttgcca aatttattcc atattttaga atatggggaa aatattctac 177780atatttattc tatggatgat gctaatacga atattataat tttttttcta gatagagtat 177840taaatattaa taagaacggg tcatttatac acaatctcgg gttatcatca tccattaata 177900taaaagaata tgtatatcaa ttagttaata atgatcatcc agataatagg ataagactaa 177960tgcttgaaaa tggacgtaga acaagacatt ttttgtccta tatatcagat acagttaata 178020tctatatatg tattttaata aatcatggat tttatataga tgccgaagac agttacggtt 178080gtacattatt acatagatgt atatatcact ataagaaatc agaatcagaa tcatacaatg 178140aattaattaa gatattgtta aataatggat ccgatgtaga taaaaaagat acgtacggaa 178200acacaccttt tatcctatta tgtaaacacg atatcaacaa cgtggaattg tttgagatat 178260gtttagagaa tgctaatata gactctgtag actttaatag atatacacct cttcattatg 178320tctcatgtcg taataaatat gattttgtaa agttattaat ttctaaagga gcaaatgtta 178380atgcgcgtaa tagattcgga actactccat tttattgtgg aattatacac ggtatctcgc 178440ttataaaact atatttggaa tcagacacag agttagaaat agataatgaa catatagttc 178500gtcatttaat aatttttgat gctgttgaat ctttagatta tctattatcc agaggagtta 178560ttgatattaa ctatcgtact atatacaacg aaacatctat ttacgacgct gtcagttata 178620atgcgtataa tacgttggtc tatctattaa acaaaaatgg tgattttgag acgattacta 178680ctagtggatg tacatgtatt tcggaagcag tcgcaaacaa caacaaaata ataatggaag 178740tactattgtc taaacgacca tctttgaaaa ttatgataca gtctatgata gcaattacta 178800aacataaaca gcataatgca gatttattga aaatgtgtat aaaatatact gcgtgtatga 178860ccgattatga tactcttata gatgtacagt cgctacagca atataaatgg tatattttaa 178920gatgtttcga tgaaatagat atcatgaaga gatgttatat aaaaaataaa actgtattcc 178980aattagtttt ttgtatcaaa gacattaata ctttaatgag atacggtaaa catccttctt 179040tcgtgaagtg cactagtctc gacgtatacg gaagtcgtgt acgtaatatc atagcatcta 179100ttagatatcg tcagagatta attagtctat tatccaagaa gctggatgcg ggagataaat 179160ggtcgtgttt tcctaacgaa ataaaatata aaatattgga aaactttaac gataacgaac 179220tatccacata tctaaaaatc ttataaacat tattaaaata taaaatctaa gtggataaaa 179280tcacactaca tcattgtttc cttttagtgc tcgacagtgt atactatttt taacgctcat 179340aaataaaaat gaaaacgatt tccgttgtta cgttgttatg cgtactacct gctgttgttt 179400attcaacatg tactgtaccc actatgaata acgctaaatt aacgtctacc gaaacatcgt 179460ttaatgataa acagaaagtt acatttacat gtgatcaggg atatcattct ttggatccaa 179520atgctgtctg tgaaacagat aaatggaaat acgaaaatcc atgcaagaaa atgtgcacag 179580tttctgatta tgtctctgaa ttatatgata agccattata cgaagtgaat tccaccatga 179640cactaagttg caacggcgaa acaaaatatt ttcgttgcga agaaaaaaat ggaaatactt 179700cttggaatga tactgttacg tgtcctaatg cggaatgtca acctcttcaa ttagaacacg 179760gatcgtgtca accagttaaa gaaaaatact catttgggga atatatgact atcaactgtg 179820atgttggata tgaggttatt ggtgcttcgt acataagttg tacagctaat tcttggaatg 179880ttattccatc atgtcaacaa aaatgtgata tgccgtctct atctaacgga ttaatttccg 179940gatctacatt ttctatcggt ggcgttatac atcttagttg taaaagtggt tttacactaa 180000cggggtctcc atcatccaca tgtatcgacg gtaaatggaa tcccatactc ccaacatgtg 180060tacgatctaa cgaaaaattt gatccagtgg atgatggtcc cgacgatgag acagatttga 180120gcaaactctc gaaagacgtt gtacaatatg aacaagaaat agaatcgtta gaagcaactt 180180atcatataat catagtggcg ttaacaatta tgggcgtcat atttttaatc tccgttatag 180240tattagtttg ttcctgtgac aaaaataatg accaatataa gttccataaa ttgctaccgt 180300aaatataaat ccgttaaaat aattaataat taataacgaa caagtatcaa aagattaaag 180360acttatagct agaatcaatt gagatgtctt cttcagtgga tgttgatatc tacgatgccg 180420ttagagcatt tttactcagg cactattata acaagagatt tattgtgtat ggaagaagta 180480acgccatatt acataatata tacaggctat ttacaagatg cgccgttata ccgttcgatg 180540atatagtacg tactatgcca aatgaatcac gtgttaaaca atgggtgatg gatacactta 180600atggtataat gatgaatgaa cgcgatgttt ctgtaagcgt tggcaccgga atactattca 180660tggaaatgtt tttcgattac aataaaaata gtatcaacaa tcaactaatg tatgatataa 180720ttaatagcgt atctataatt ctagctaatg agagatatag aagcgctttt aacgacgatg 180780gtatatacat ccgtagaaat atgattaaca agttgtacgg atacgcatct ctaactacta 180840ttggcacgat cgctggaggt gtttgttatt atctgttgat gcatctagtt agtttgtata 180900aataattatt tcaatatact agttaaaatt ttaagatttt aaatgtataa aaaactaata 180960acgtttttat ttgtaatagg tgcattagca tcctattcga ataatgagta cactccgttt 181020aataaactga gtgtaaaact ctatatagat ggagtagata atatagaaaa ttcatatact 181080gatgataata atgaattggt gttaaatttt aaagagtaca caatttctat tattacagag 181140tcatgcgacg tcggatttga ttccatagat ataaatgtta taaacgacta taaaattatt 181200gatatgtata ccattgactc gtctactatt caacgcagag gtcacacgtg tagaatatct 181260accaaattat catgccatta tgataagtac ccttatattc acaaatatga tggtgatgag 181320cgacaatatt ctattactgc agagggaaaa tgctataaag gaataaaata tgaaataagt 181380atgatcaacg atgatactct attgagaaaa catactctta aaattggatc tacttatata 181440tttgatcgtc atggacatag taatacatat tattcaaaat atgattttta aaaatttaaa 181500atatattatc acttcagtga cagtagtcaa ataacaaaca acaccatgag atatattata 181560attctcgcag ttttgttcat taatagtata catgctaaaa taactagtta taagtttgaa 181620tccgtcaatt ttgattccaa aattgaatgg actggggatg gtctatacaa tatatccctt 181680aaaaattatg gcatcaagac gtggcaaaca atgtatacaa atgtaccaga aggaacatac 181740gacatatccg catttccaaa gaatgatttc gtatctttct gggttaaatt tgaacaaggc 181800gattataaag tggaagagta ttgtacggga ctatgcgtcg aagtaaaaat tggaccaccg 181860actgtaacat tgactgaata cgacgaccat atcaatttgt acatcgagca tccgtatgct 181920actagaggta gcaaaaagat tcctatttac aaacgcggtg acatgtgtga tatctacttg 181980ttgtatacgg ctaacttcac attcggagat tctaaagaac cagtaccata tgatatcgat 182040gactacgatt gcacgtctac aggttgcagc atagactttg tcacaacaga aaaagtgtgc 182100gtgacagcac agggagccac agaagggttt ctcgaaaaaa ttactccatg gagttcgaaa 182160gtatgtctga cacctaaaaa gagtgtatat acatgcgcaa ttagatccaa agaagatgtt 182220cccaatttca aggacaaaat ggccagagtt atcaagagaa aatttaatac acagtctcaa 182280tcttatttaa ctaaatttct cggtagcaca tcaaatgatg ttaccacttt tcttagcatg 182340cttaacttga ctaaatattc ataactaatt tttattaatg atacaaaaac gaaataaaac 182400tgcatattat acactggtta acgcccttat aggctctaac cattttcaag atgaggtccc 182460tgattatagt ccttctgttc ccctctatca tctactccat gtctattaga caatgtgaga 182520aaactgaaga ggaaacatgg ggattgaaaa tagggttgtg tataattgcc aaagatttct 182580atcccgaaag aactgattgc agtgttcatc tcccaactgc aagtgaagga ttgataactg 182640aaggcaatgg attcagggat atacgaaaca ccgataaatt ataaaaaaag caatgtgtcc 182700gctgtttccg ttaataatac tatttttgta actggcggat tattcataaa taactctaat 182760agcacgatcg tggttaacaa tatggaaaaa cttgacattt ataaagacaa acaatggtcg 182820attatagaaa tgcctatggc tagggtatat cacggcatcg actcgacatt tggaatgtta 182880tattttgccg gaggtctatc cgttaccgaa caatatggta atttagagaa aaacaacgag 182940atatcttgtt acaatcctag aacgaataag tggtttgata tttcatatac tatttataag 183000atatccatat catcattgtg taaactaaat aacgtcttct atgtatttag taaggacatt 183060ggatatgtgg aaaagtatga tggtgcatgg aagttagtac atgatcgtct ccccgctata 183120aaggcattat caacttctcc ttattgattg aaaatgaaaa tataaatagt ttttatgtat 183180agcagtatta ccctatagtt ttattgctta ctactaacat ggatacagat gttacaaatg 183240tagaagatat cataaatgaa atagatagag agaaagaaga aatactaaaa aatgtagaaa 183300ttgaaaataa taaaaacatt aacaagaatc atccaagtgg atatattaga gaagcactcg 183360ttattaatac cagtagtaat agtgattcca ttgataaaga agttatagaa tgtatctgtc 183420acgatgtagg aatatagatc atatctacta atttttataa tcgatacaaa acataaaaaa 183480caactcgtta ttacatagca ggcatggaat ccttcaagta ttgttttgat aacgatggca 183540agaaatggat tatcggaaat actttatatt ctggtaattc aatactctat aaggtcagaa 183600aaaatttcac tagttcgttc tacaattacg taatgaagat agatcacaaa tcacacaagc 183660cattgttgtc tgaaatacga ttctatatat ctgtattgga tcctttgact atcgacaact 183720ggacacggga acgtggtata aagtatttgg ctattccaga tctgtatgga attggagaaa 183780ccgatgatta tatgttcttc gttataaaga attcgggaag agtattcgcc ccaaaggata 183840ctgaatcagt cttcgaagca tgcgtcacta tgataaacac gttagagttt atacactctc 183900gaggatttac ccatggaaaa atagaaccga ggaatatact gattagaaat aaacgtcttt 183960cactaattga ctattctaga actaacaaac tatacaagag tggaaactca catatagatt 184020acaacgagga catgataact tcaggaaata tcaattatat gtgtgtagac aatcatcttg 184080gagcaacagt ttcaagacga ggagatttag aaatgttggg atattgcatg atagaatggt 184140tcggtggcaa acttccatgg aaaaacgaaa gtagtataaa agtaataaaa caaaaaaaag 184200aatataaaaa atttatagct actttctttg aggactgttt tcctgaagga aatgaacctc 184260tggaattagt tagatatata gaattagtat acacgttaga ttattctcaa actcctaatt 184320atgacagact acgtaaactg tttatacaag attgaaatta tattcttttt ttatagagtg 184380tggtagtgtt acggatattt aatattagac tatctctatc gcgctacacg accaatatcg 184440attactatgg atatcttcta tgaaaggaga gaatgtattc atttctccag cgtcaatctc 184500gtcagtattg acaatactgt attatggagc taatggatcc actgctgaac agctatcgaa 184560atatgtagaa aaggaggaga acacggataa ggttagcgct cagaatatct cattcaaatc 184620catgaataaa gtatatgggc gatattctgc cgtgtttaaa gattcctttt tgagaaaaat 184680tggcgataag tttcaaactg ttgacttcac tgattgtcgc actatagatg caatcaacaa 184740gtgtgtagat atctttactg aggggaaaat caatccacta ttggatgaac cattgtctcc 184800tagcaattag tgccgtatac tttaaagcaa aatggttgac gccattcgaa aaggaattta 184860ccagtgatta tcccttttac gtatcaccaa cggaaatggt agacgtaagt atgatgtcta 184920tgtacggcga gctatttaat cacgcatctg taaaagaatc attcggcaac ttttcaatca 184980tagaactgcc atatgttgga gatactagta tgatggtcat tcttccagac aagattgatg 185040gattagaatc catagaacaa aatctaacag atacaaattt taagaaatgg tgtgacttta 185100tggatgctat gtttatagat gttcacattc ccaagtttaa ggtaacaggt tcgtataatc 185160tggtggatac tctagtaaag tcaggactga cagaggtgtt cggttcaact ggagattata 185220gcaatatgtg taattcagat gtgagtgtcg acgctatgat ccacaaaacg tatatagatg 185280tcaatgaaga gtatacagaa gcagctgcag caacttctgt actagtggca gactgtgcat 185340caacagttac aaatgagttc tgtgcagatc atccgttcat ctatgtgatt aggcatgttg 185400atggaaaaat tcttttcgtt ggtagatatt gctctccgac aactaattgt taaccatttt 185460ttttaaaaaa aatagaaaaa acatgtggta ttagtgcagg tcgttattct tccaattgca 185520attggtaaga tgacggccaa ctttagtacc cacgtctttt caccacagca ctgtggatgt 185580gacagactga ccagtattga tgacgtcaaa caatgtttga ctgaatatat ttattggtcg 185640tcctatgcat accgcaacag gcaatgcgct ggacaattgt attccacact cctctctttt 185700agagatgatg cggaattagt gttcatcgac attcgcgagc tggtaaaaaa tatgccgtgg 185760gatgatgtca aagattgtac agaaatcatc cgttgttata taccggatga gcaaaaaacc 185820atcagagaga tttcggccat catcggactt tgtgcatatg ctgctactta ctggggaggt 185880gaagaccatc ccactagtaa cagtctgaac gcattgtttg tgatgcttga gatgctaaat 185940tacgtggatt ataacatcat attccggcgt atgaattgat gagttgtaca tcttgacatt 186000ttctttcttc tcttctccct ttcttctctt ctcccttcct ccctcttctc cctttcccag 186060aaacaaactt ttttacccac tataaaataa aatgagtata ctacctatta tatttcttcc 186120tatatttttt tattcttcat tcgttcagac ttttaacgcg cctgaatgta tcgacaaagg 186180gcaatatttt gcatcattca tggagttaga aaacgagcca gtaatcttac catgtcctca 186240aataaatacg ctatcatccg gatataatat attagatatt ttatgggaaa aacgaggagc 186300ggataatgat agaattatac cgatagataa tggtagcaat atgctaattc tgaacccgac 186360acaatcagac tctggtattt atatatgcat taccacgaac gaaacctact gtgacatgat 186420gtcgttaaat ttgacaatcg tgtctgtctc agaatcaaat atagatctta tctcgtatcc 186480acaaatagta aatgagagat ctactggcga aatggtatgt cccaatatta atgcatttat 186540tgctagtaac gtaaacgcag atattatatg gagcggacat cgacgcctta gaaataagag 186600acttaaacaa cggacacctg gaattattac catagaagat gttagaaaaa atgatgctgg 186660ttattataca tgtgttttag aatatatata cggtggcaaa acatataacg taaccagaat 186720tgtaaaatta gaggtacggg ataaaataat accttctact

atgcaattac cagatggcat 186780tgtaacttca ataggtagta atttgactat tgcatgcaga gtatcgttga gacctcccac 186840aacggacacc gacgtctttt ggataagtaa tggtatgtat tacgaagaag atgatgggga 186900cggaaacggt agaataagtg tagcaaataa aatctatatg accgataaga gacgtgttat 186960tacatcccgg ttaaacatta atcctgtcaa ggaagaagat gctacaacgt ttacgtgtat 187020ggcgtttact attcctagca tcagcaaaac agttactgtt agtataacgt gaatgtatgt 187080tgttacattt ccatgtcaat tgagtttata agaattttta tacattatct tccaacaaac 187140aattgacgaa cgtattgcta tgattaactc ccacgatact atgcatatta ttaatcatta 187200acttgcagac tatacctagt gctattttga catactcatg ttcttgtgta attgcggtat 187260ctatattatt aaagtacgta aatctagcta tagttttatt atttaatttt agataatata 187320ccgtctcctt atttttaaaa attgccacat cctttattaa atcatgaatg ggaatttcta 187380tgtcatcgtt agtatattgt gaacaacaag agcagatatc tataggaaag ggtggaatgc 187440gatacattga tctatgtagt tttaaaacac acgcaaactt tgaagaattt atataaatca 187500ttccatcgat acatccttct atgttgagat gtatatatcc aggaattcgt ttattaatat 187560cgggaaatgt ataaactaaa acattgcccg aaagcggtgc ctctatctgc gttatatccg 187620ttcttaactt acaaaatgta accaatacct ttgcatgact tgttttgttc ggcaacgtta 187680gtttaaactt gacgaatgga ttaattacaa tagcatgatc cgcgcatcta ttaagttttt 187740ttactttaac gcccttgtat gtttttacag agactttatc taaatttcta gtgcttgtat 187800gtgttataaa tataacggga tatagaactg aatcacctac cttagatacc caattacatt 187860ttatcagatc cagataataa acaaattttg tcgccctaac taattctata ttgttatata 187920ttttacaatt ggttatgata tcatgtaata acttggagtc taacgcgcat cgtcgtacgt 187980ttatacaatt gtgatttagt gtagtatatc tacacatgta tttttccgca ctatagtatt 188040ctggactagt gataaaacta tcgttatatc tatcttcaat gaactcatcg agatattgct 188100ctctgtcata ttcatacacc tgcataaact ttctagacat cttacaatcc gtgttatttt 188160aggatcatat ttacatattt acgggtatat caaagatgtt agattagtta atgggaatcg 188220tctataataa tgaatattaa acaattatat gaggactttt accacaaagc atcataaaaa 188280tgagtcgtcg tctgatttat gttttaaata tcaaccgcga atcaactcat aaaatacaag 188340agaatgaaat atatacatat tttagtcatt gcaatataga ccatacttct acagaacttg 188400attttgtagt taaaaactat gatctaaaca gacgacaaca tgtaactggg tatactgcac 188460tacactgcta tttgtataat aattacttta caaacgatgt actgaagata ttattaaatc 188520atggagtgga tgtaacgatg aaaaccagta gcggacgtat gcctgtttat atattgctta 188580ctagatgttg taatatttca catgatgtag tgatagatat gatagacaaa gataaaaacc 188640acttattaca tagagactat tccaacctat tactagagta tataaaatct cgttacatgt 188700tattgaagga agaggatatc gatgagaaca tagtatccac tttattagat aagggaatcg 188760atcctaactt taaacaagac ggatatacag cgttacatta ttattatttg tgtctcgcac 188820acgtttataa accaggtgag tgtagaaaac cgataacgat aaaaaaggcc aagcgaatta 188880tttctttgtt tatacaacat ggagctaatc taaacgcgtt agataattgt ggtaatacac 188940cattccattt gtatcttagt attgaaatgt gtaataatat tcatatgact aaaatgctgt 189000tgacttttaa tccgaatttc gaaatatgta ataatcatgg attaacgcct atactatgtt 189060atataacttc cgactacata caacacgata ttcttgttat gttaatacat cactatgaaa 189120caaatgttgg agaaatgccg atagatgagc gtcgtatgat cgtattcgag tttatcaaaa 189180catattctac acgtccggca gattcgataa cttatttgat gaataggttt aaaaatataa 189240atatttatac ccgctatgaa ggaaagacat tattacacgt agcatgtgaa tataataata 189300cacaagtaat agattatctt atacgtatca acggagatat aaatgcgtta accgacaata 189360acaaacacgc tacacaactc attatagata acaaagaaaa ttccccatat accattaatt 189420gtttactgta tatacttaga tatattgtag ataagaatgt gataagatcg ttggtggatc 189480aacttccatc tctacctatc tttcgtcgct tatcatacta gtcatatcct aaatgttgat 189540catattccac caaatgattg tgaaagagat tgagattaaa tcgtctaaca aacaattagt 189600ttttatgaca ttaacatata ataaataaat taatcattat tgacttaacg atgacgaaag 189660ttatcatcat cttaggattc ttgattatta atacaaattc attgtctatg aaatgtgaac 189720aaggtgtctc atattataat tcacaagaat taaagtgttg taaactatgt aagccaggaa 189780catattcaga tcatcgatgt gataaataca gcgataccat ttgtggacat tgtccgagtg 189840acacattcac gtcaatatat aatcgttctc cttggtgtca tagttgtaga ggtccatgtg 189900gtactaatcg agtagaggtc acaccttgta cacctaccac aaatagaatc tgtcattgtg 189960actcgaatag ttattgtctc cttaaagctt ctgatggtaa ctgtgttaca tgtgctccta 190020aaacaaaatg tggtcgtggg tatggaaaga aaggagaaga tgaaatgggt aataccattt 190080gtaagaaatg tcggaagggt acttattcag atattgtatc tgactctgat caatgtaaac 190140caatgacaag ataagactta ctcgcatcta ctggatagac ataaaatatc ctcctcgtaa 190200taatgaaata taaatataca ctaattatta atatcaataa caatcgagta ttaatatata 190260ggtcattttt aaatcccttt tgggttccgt cccaaacggc gtttcggtct gcgtcgccgc 190320catggccatg ccgagcctct ccgcgtgctc ctccatcgag gacgacttca actatggcag 190380ctcggtggcg tctgccagcg tgcacatacg aatggcattt ctaagaaaag tctacggtat 190440cctttgtcta caatttcttt taacaacggc aacaactgca gtatttttat actttgactg 190500catgcggaca tttatacaag ggagtcctgt tctaatattg gcatcaatgt tcggatctat 190560aggcttgatt ttcgcattga ctttacacag acataaacat cccctgaatc tgtacctgct 190620ttgtggattt acactgtcgg aatctctaac gctggcctct gttgttactt tctatgatgt 190680gcatgtcgtt atgcaagctt tcatgctgac tactgcagcg tttcttgctc tgactacata 190740tactctacaa tcaaagagag atttcagtaa acttggagca ggattgtttg ctgctttgtg 190800gattttaatt ttgtcaggac tcttggggat atttgtgcaa aatgagacag tgaagctggt 190860cctgtctgct tttggggccc ttgtattctg tggattcatt atctatgaca cgcactcact 190920aatacataag ctctcgcctg aagagtatgt gttagcctct atcaatctct acttggatat 190980catcaatctg ttcttgcatc tgttgcagct tttggaagta tctaataaga aataaagttt 191040aaaatagaat taataaaaac atataggtca ttttttaaac atggattgga aaccaaggta 191100gttagttaat acacacaaga tatatttttt tcacatcatc cacccatggg taacaccaag 191160gttgttagtt aataatatac aagatatttt ttctcactct gatccatgta aaccaaggac 191220gagataagac actctcattc ctcatccaca accccattaa aaaatggaaa ttaaagccct 191280ctattagcat agacggctac aggtctacca tcaggttaac cttcgtctac cttcacaatg 191340gcctttcctt gtgcccagtt cagaccctgt cattgccacg ctactaagga ctccctgaat 191400accgtggccg acgtcagaca ttgtctgact gaatacatcc tgtgggtttc tcatagatgg 191460acccatagag aaagcgcagg gtctctctac aggcttctca tctctttcag aactgatgca 191520acggagctct ttggtggtga gttgaaggat tcacttccgt gggacaattg cgtggagatc 191580attaaatgtt tcatcagaaa tgactccatg aaaaccgccg aagaacttcg tgcaatcatt 191640ggactttgta ctcaatcagc tatcgtctct ggaagagtct tcaacgataa gtatatcgac 191700atactactta tgctgcgaaa gattctgaac gagaacgact atctcaccct cttggatcat 191760atccgcactg ctaaatacta aatctccttc atgctctctc actacacttt ttatcatctt 191820atgaggaatg attgccttta tcatttttcg tgaaatagga ataattagca ccagaatagc 191880tatggattat tgtggtagag agtgcactat tctatgtcgt ctactggatg aagatgtgac 191940gtacaaaaaa ataaaactag aaattgaaac gtgtcacaac ttatcaaaac atatagatag 192000acgaggaaac aatgcgctac attgttacgt ctccaataaa tgcgatacag acattaagat 192060tgttcggctg ttactctctc gcggagtcga gagactttgt agaaacaacg aaggattaac 192120tccgctagga gtatacagta agcatagata cgtaaaatct cagattgtgc atctactgat 192180atccagctat tcaaattcct ctaacgaact caagtcgaat ataaatgatt tcgatctgta 192240ttcggataat atcgacttac gtctgctaaa atacctaatt gtggataaac ggatacgtcc 192300gtccaagaat acgaattatg caatcaatgg tctcggattg gtggatatat acgtaacgac 192360gcctaatccg agaccagaag tattgctatg gcttcttaaa tcagaatgtt acagcaccgg 192420ttacgtattt cgtacctgta tgtacgacag tgatatgtgt aagaactctc ttcattacta 192480tatatcgtct catagagaat ctcaatctct atccaaggat gtaattaaat gtttgatcga 192540taacaatgtt tccatccatg gcagagacga aggaggatct ttacccatcc aatactactg 192600gtcttgctca accatagata tagagattgt taaattatta ttaataaagg atgtggacac 192660gtgtagagta tacgacgtca gccctatatt agaggcgtat tatctaaaca agcgatttag 192720agtaacccca tataatgtag acatggaaat cgttaatctt cttattgaga gacgtcatac 192780tcttgtcgac gtaatgcgta gtattacttc gtacgattcc agagaatata accactacat 192840catcgataac attctaaaga gatttagaca acaggatgta caagccatgt tgataaacta 192900cttacattac ggcgatatgg taagtatacc tatcattcaa tgcatgttgg ataacggagc 192960aaccatggat aagacgacgg acaacaacta tcctctacac gactactttg ttaataataa 193020tctcgtcgat gtaaacgtcg taaggtttat cgtggaaaat atggacacgc ggctgtaaat 193080cacgtatcga acaatggccg tctatgtatg tacggtctga tattatcgag atttaataat 193140tgcgggtatc actgttatga aaccatacta atagatgtat ttgatatact aagcaagtac 193200atggatgata tagatatgat cgataactct actatattac gcggtcgatg tcaataatat 193260acaatttgca aagcggttat tggaatatgg agcgagtgtt acaacatcac gctcgataat 193320caatacggcc atccagaaaa gcagttacca aagagaaaac aaaacgagga tagttgattt 193380attacttagc taccatccca ctctagagac tatgattgac gcatttaata gagatatacg 193440ctatctatat cctgaaccat tattcgcctg tatcagatac gccttaatca tagatgatga 193500ttttccttct aaagtaaagt atgatatcgc cggtcgtcat aaggaactaa agcgctatag 193560agcagacatt aatagaatga agaatgccta catatcaggc gtctccatgt ttgatatatt 193620atttaaacaa agcaaacgcc acagactgag atacgcaaag aatccgacat caaatggtac 193680aaaaaagaac taacgtccat cattacagaa actgtaaaga acaatgagag gatcgactcc 193740atagtggaca acattaatac agacgataac ttgatttcga aattacccat ggagatactt 193800tattactcca ttaaataatt tatcatggag cgataatgtc ctgtttcatt tgtttccatg 193860acatattaca aaatcgattc cgtccaagat gataaaaaca tttaccggca tcataaacac 193920ggagtttatt ttatatgtct cgcataaaca ttactaaaaa aatatattgt tctgtttttc 193980tttcacatct ttaattatga aaaagtaaat cattatgaga tggacgagat tgtacgcatc 194040gttcgcgaca gtatgtggta catacctaac gtatttatgg acgacggtaa gaatgaaggt 194100cacgtttctg tcaacaatgt ctgtcatatg tatttcacgt tctttgatgt gaatacatcg 194160tctcatctgt ttaagctagt tattaaacac tgcgatctga ataaacgagg taactctcca 194220ttacattgct atacgatgaa tacacgattt aatccatctg tattaaagat attgttacac 194280cacggcatgc gtaactttga tagcaaggat gaccactatc aatcgataac aagatctttg 194340atatactaac ggacaccatt gatgacttta gtaaatcatc cgatctattg ctgtgttatc 194400ttagatataa attcaatggg agcttaaact attacgttct gtacaaagga tccgacccta 194460attgcgccga cgaggatgaa ctcacttctc ttcattacta ctgtaaacac atatccacgt 194520tctacgaaag caattattac aagtcaagtc acactaagat gcgagccgag aagcgattca 194580tctacgcgat aatagattat ggagcaaaca ttaacgcggt tacacactta ccttcaacag 194640tataccaaac atagtcctcg tgtggtgtat gctcttttat ctcgaggata cgtaataatc 194700ttgattgtac acccatcatg gaacgattgt gcaacaggtc atattctcat aatgttactc 194760aattggcacg aacaaaagga agaaggacaa catctacttt atctattcat aaaacataat 194820caaggataca ctctcaatat actacggtat ctattagata ggttcgacat tcagaaagac 194880gaatactata ataccgcctt tcaaaattgt aacaacaatg ttgcctcata catcggatac 194940gacatcaacc ttccgactaa agacggtatt cgacttggtg tttgaaaaca gaaacatcat 195000atacaaggcg gatgttgtga atgacatcat ccaccacaga ctgaaagtat ctctacctat 195060gattaaatcg ttgttctaca agatgtctct ccctacgacg attactacgt aaaaaagata 195120ctagcctact gcctattaag ggacgagtca ttcgcggaac tacatagtaa attctgttta 195180aacgaggact ataaaagtgt atttatgaaa aatatatcat tcgataagat agattccatc 195240atcgtgacat aagtcgcctt aaagagattc gaatctccga caccgacctg tatacggtat 195300cacagctatc ttaaagccat acattcagac agtcacattt catttcccat gtacgacgat 195360ctcatagaac agtgccatct atcgatggag cgtaaaagta aactcgtcga caaagcactc 195420aataaattag agtctaccat cggtcaatct agactatcgt atttgcctcc ggaaattatg 195480cgcaatatca tctaaacagt atgttgtacg gaaagaacca ttacaaatat tatccatgat 195540agaaagaaaa tatctatatg attggagaag taggaaacag gaacaagacg acgattacta 195600cattattaaa tcatgaagtc cgtattatac tcgtatatat tgtttctctc atgtataata 195660ataaacggaa gagatatagc accgcatgca ccatccgatg gaaagtgtaa agacaacgaa 195720tacaaacgcc ataatttgtg tccgggaaca tacgcttcca gattatgcga tagcaagact 195780aacacacaat gtacgccgtg tggttcgggt accttcacat ctcgcaataa tcatttaccc 195840gcttgtctaa gttgtaacgg aagacgcgat cgtgtaacac gactcacaat agaatctgtg 195900aatgctctcc cggatattat tgtcttctca aaggatcatc cggatgcaag gcatgtgttt 195960cccaaacaaa atgtggaata ggatacggag tatccggaga cgtcatctgt tctccgtgtg 196020gtctcggaac atattctcac accgtctctt ccgcagataa atgcgaaccc gtacccagta 196080atacctttaa ctatatcgat gtggaaatta atctgtatcc agttaacgac acgtcgtgta 196140ctcggacgac cactaccggt ctcagcgaat ccatctcaac gtcggaacta actattacta 196200tgaatcataa agactgcgat cccgtctttc gtgatggata cttctccgtc cttaataagg 196260tagcgacttc aggtttcttt acaggagaaa ggtgtgcact ctgaatttcg agattaaatg 196320caataacaaa gattcttcct ccaaacagtt aacgaaagca aagaatgata ctatcatgcc 196380gcattcggag acagtaactc tagtgggcga catctatata ctatatagta ataccaatac 196440tcaagactac gaaactgata caatctctta tcatgtgggt aatgttctcg atgtcgatag 196500ccatatgccc ggtagttgcg atatacataa actgatcact aattccaaac ccacccactt 196560tttatagtaa gtttttcacc cataaataat aaatacaata attaatttct cgtaaaagta 196620gaaaatatat tctaatttat tgcacggtaa ggaagtagaa tcataaagaa cagtactcaa 196680tcaatagcaa ttatgaaaca atatatcgta ctggcatgca tgtgcctggc ggcagctgct 196740atgcctgcca gtcttcagca atcatcctca tcctcctcct cgtgtacgga agaagaaaac 196800aaacatcata tgggaatcga tgttattatc aaagtcacaa agcaagacca aacaccgacc 196860aatgataaga tttgccaatc cgtaacggaa attacagagt ccgagtcaga tccagatccc 196920gaggtggaat cagaagatga ttccacatca gtcgaggatg tagatcctcc taccacttat 196980tactccatca tcggtggagg tctgagaatg aactttggat tcaccaaatg tcctcagatt 197040aaatccatct cagaatccgc tgatggaaac acagtgaatg ctagattgtc cagcgtgtcc 197100ccaggacaag gtaaggactc tcccgcgatc actcatgaag aagctcttgc tatgatcaaa 197160gactgtgagg tgtctatcga catcagatgt agcgaagaag agaaagacag cgacatcaag 197220acccatccag tactcgggtc taacatctct cataagaaag tgagttacga agatatcatc 197280ggttcaacga tcgtcgatac aaaatgtgtc aagaatctag agtttagcgt tcgtatcgga 197340gacatgtgca aggaatcatc tgaacttgag gtcaaggatg gattcaagta tgtcgacgga 197400tcggcatctg aaggtgcaac cgatgatact tcactcatcg attcaacaaa actcaaagcg 197460tgtgtctgaa tcgataactc tattcatctg aaattggatg agtagggtta atcgaacgat 197520tcaggcacac cacgaattaa aaaagtgtac cggacactat attccggttt gcaaaacaaa 197580aatgttctta actacattca caaaaagtta cctctcgcga cttcttcttt ttctgtctca 197640atagtgtgat acgattatga cactattcct attcctattc ctattcctat ttcctttcag 197700ggtatcacaa aaatattaaa cctctttctg atggtctcat aaaaaaagtt ttacaaaaat 197760atttttattc tctttctctc tttgatggtc tcataaaaaa agttttacaa aaatattttt 197820attctctttc tctctttgat ggtctcataa aaaaagtttt acaaaaatat ttttattctc 197880tttctctctt tgatggtctc ataaaaaaag ttttacaaaa atatttttat tctctttctc 197940tctttgatgg tctcataaaa aaagttttac aaaaatattt ttattctctt tctctctttg 198000atggtctcat aaaaaaagtt ttacaaaaat atttttattc tctttctctc tttgatggtc 198060tcataaaaaa agttttacaa aaatattttt attctctttc tctctttgat ggtctcataa 198120aaaaagtttt acaaaaatat ttttattctc tttctctctt tgatggtctc ataaaaaaag 198180ttttacaaaa atatttttat tctctttctc tctttgatgg tctcataaaa aaagttttac 198240aaaaatattt ttattctctt tctctctttg atggtctcat aaaaaaagtt ttacaaaaat 198300atttttattc tctttctctc tttgatggtc tcataaaaaa agttttacaa aaatattttt 198360attctctttc tctctttgat ggtctcataa aaaaagtttt acaaaaatat ttttattctc 198420tttctctctt tgatggtctc ataaaaaaag ttttacaaaa atatttttat tctctttctc 198480tctttgatgg tctcataaaa aaagttttac aaaaatattt ttattctctt tctctctttg 198540atggtctcat aaaaaaagtt ttacaaaaat atttttattc tctttctctc tttgatggtc 198600tcataaaaaa agttttacaa aaatattttt attctctttc tctctttgat ggtctcataa 198660aaaaagtttt acaaaaatat ttttattctc tttctctctt tgatggtctc ataaaaaaag 198720ttttacaaaa atatttttat tctctttctc tctttgatgg tctcataaaa aaagttttac 198780aaaaatattt ttattctctt tctctctttg atggtctcat aaaaaaagtt ttacaaaaat 198840atttttattc tctttctctc tttgatggtc tcataaaaaa agttttacaa aaatattttt 198900attctctttc tctctttgat ggtctcataa aaaaagtttt acaaaaatat ttttattctc 198960tttctctctt tgatggtctc ataaaaaaag ttttacaaaa atatttttat tctctttctc 199020tctttgatgg tctcataaaa aaagttttac aaaaatattt ttattctctt tctctctttg 199080atggtatcat aaaaaaagtt ttacaaaaat atttttattc tctttctctc tttgatggtc 199140tcataaaaaa agttttacaa aaatattttt attctctttc tctctttgat ggtctcataa 199200aaaaagtttt acaaaaatat ttttattctc tttctctctt tgatggtctc ataaaaaaag 199260ttttacaaaa atatttttat tctctttctc tctttgatgg tctcataaaa aaagttttac 199320aaaaatattt ttattctctt tctctctttg atggtctcat aaaaaaagtt ttacaaaaat 199380atttttattc tctttctctc tttgatggtc tcataaaaaa agttttacaa aaatattttt 199440attctctttc tctctttgat ggtctcataa aaaaagtttt acaaaaatat ttttattctc 199500tttctctctt tgatggtctc ataaaaaaag ttttacaaaa atatttttat tctctttctc 199560tctttgatgg tctcataaaa aaagttttac aaaaatattt ttattctctt tctctctttg 199620atggtctcat aaaaaaagtt ttacaaaaat atttttattc tctttctctc tttgatggtc 199680tcataaaaaa agttttacaa aaatattttt attctctttc tctctttgat ggtctcataa 199740aaaaagtttt acaaaaatat ttttattctc tttctctctt tgatggtctc ataaaaaaag 199800ttttacaaaa atatttttat tctctttctc tctttgatgg tctcataaaa aaagttttac 199860aaaaatattt ttattctctt tctctctttg atggtctcat aaaaaaagtt ttacaaaaat 199920atttttattc tctttctctc tttgatggtc tcataaaaaa agttttacaa aaatattttt 199980attctctttc tctctttgat ggtctcataa aaaaagtttt acaaaaatat ttttattctc 200040tttctctctt tgatggtctc ataaaaaaag ttttacaaaa atatttttat tctctttctc 200100tctttgatgg tctcataaaa aaagttttac aaaaatattt ttattctctt tctctctttg 200160atggtctcat aaaaaaagtt ttacaaaaat atttttattc tctttctctc tttgatggtc 200220tcataaaaaa agttttacaa aaatattttt attttctttc tctctttgat ggtctcataa 200280aaaatattaa acctctttct gatggtgtca ctaaaatatt tttattctca ttctcatttt 200340ctctttctct cttcaatgga gtcataaaat atttttattc tctttctctc ttcgatggtc 200400tcacaaaaat attaaacctc tttctgatgg tgtcactaaa atatttttat tctcattctc 200460attttctctt tctctcttca atggagtcat aaaatatttt tattctcttt ctctcttcga 200520tggtctcaca aaaatattaa acctctttct gatggagtcg taaaaaagtt ttatctcttt 200580ctctcttcga tggtctcact aaaatatttt ttattctctt tctgatgcat caactatttc 200640ttaaacaata acgtccaaca acatatactc gtcgagctta tcaacatccc ctatgcccat 200700ctaggttacc agacaattgt atatcataaa ataatgttta taatttacac gttaaaatca 200760tataataaaa cgtagatcgt ataatatttt ttggtatata aatgatctag taaaatccat 200820gtaggggata ctgctcacat tttttctttg gtacaaaatt tcacacaagt ttttatacag 200880acaaattctt gtccatatat tttaaaacat tgacttttgt actaagaaaa atatctagac 200940taactatctc tttctctttc tctcttcgat ggtctcacaa aaatattaaa cctctttctg 201000atggagtcgt aaaaaagttt tatctctttc tctcttcgat ggtctcacaa aaatattaaa 201060cctctttctg atggagtcgt aaaaaagttt tatctctttc tctcttcgat ggtctcacaa 201120aaatattaaa cctctttctg atggagtcgt aaaaaagttt tatctctttc tctcttcgat 201180ggtctcacaa aaatattaaa cctctttctg atggagtcgt aaaaaagttt tatctctttc 201240tctcttcgat ggtctcacaa aaatattaaa cctctttctg atggagtcgt aaaaaagttt 201300tatctctttc tctcttcgat ggtctcacaa aaatattaaa cctctttctg atggagtcgt 201360aaaaaagttt tatctctttc tctcttcgat ggtctcacaa aaatattaaa cctctttctg 201420atggagtcgt aaaaaagttt tatctctttc tctcttcgat ggtctcacaa aaatattaaa 201480cctctttctg atggagtcgt aaaaaagttt tatctctttc tctcttcgat ggtctcacaa 201540aaatattaaa cctctttctg atggagtcgt aaaaaagttt tatctctttc tctcttcgat 201600ggtctcacaa aaatattaaa cctctttctg atggagtcgt aaaaaagttt tatctctttc 201660tctcttcgat ggtctcacaa aaatattaaa cctctttctg atggagtcgt aaaaaagttt 201720tatctctttc tctcttcgat ggtctcacaa aaatattaaa cctctttctg atggagtcgt 201780aaaaaagttt tatctctttc tctcttcgat ggtctcacaa

aaatattaaa cctctttctg 201840atggagtcgt aaaaaagttt tatctctttc tctcttcgat ggtctcacaa aaatattaaa 201900cctctttctg atggagtcgt aaaaaagttt tatctctttc tctcttcgat ggtctcacaa 201960aaatattaaa cctctttctg atggagtcgt aaaaaagttt tatctctttc tctcttcgat 202020ggtctcacaa aaatattaaa cctctttctg atggagtcgt aaaaaagttt tatctctttc 202080tctcttcgat ggtctcacaa aaatattaaa cctctttctg atggagtcgt aaaaaagttt 202140tatctctttc tctcttcgat ggtctcacaa aaatattaaa cctctttctg atggagtcgt 202200aaaaaagttt tatctctttc tccttcgatg gtctcacaaa aatattaaac ctctttctga 202260tggagtcgta aaaaagtttt atctctttct ctcttcgatg gtctcacaaa aatattaaac 202320ctctttctga tggagtcgta aaaaagtttt atctctttct ctcttcgatg gtctcacaaa 202380aatattaaac ctctttctga tggtctctat aaagcgatcg atctttctta cactctagag 202440tttcctacag tcatgggtca cacatttttt tctagacact aaataaaat 20248922908DNAArtificial Sequencepolynucleotide comprising p7.5k promoter-DsReD 22cctgcaggtc aattcggtag ttgcgatata cataaactga tcactaattc caaacccacc 60cactttttat agtaagtttt tcacccataa ataataaata caataattaa tttctcgtaa 120aagtagaaaa tatattctaa tttattgcac ggtaaggaag tagtcgaaac gaattcgccc 180ttgcttgcaa gccaccatgg cctcctccga ggacgtcatc aaggagttca tgcgcttcaa 240ggtgcgcatg gagggctccg tgaacggcca cgagttcgag atcgagggcg agggcgaggg 300ccgcccctac gagggcaccc agaccgccaa gctgaaggtg accaagggcg gccccctgcc 360cttcgcctgg gacatcctgt ccccccagtt ccagtacggc tccaaggtgt acgtgaagca 420ccccgccgac atccccgact acaagaagct gtccttcccc gagggcttca agtgggagcg 480cgtgatgaac ttcgaggacg gcggcgtggt gaccgtgacc caggactcct ccctgcagga 540cggctccttc atctacaagg tgaagttcat cggcgtgaac ttcccctccg acggccccgt 600aatgcagaag aagactatgg gctgggaggc ctccaccgag cgcctgtacc cccgcgacgg 660cgtgctgaag ggcgagatcc acaaggccct gaagctgaag gacggcggcc actacctggt 720ggagttcaag tccatctaca tggccaagaa gcccgtgcag ctgcccggct actactacgt 780ggactccaag ctggacatca cctcccacaa cgaggactac accatcgtgg agcagtacga 840gcgcgccgag ggccgccacc acctgttcct gtaggcgcgc ctataagggc gaattcgcgg 900cctcgacg 908232349DNAArtificial Sequencepolynucleotide comprising mouse IL-12 23accggtcgcc accatgtgcc ctcagaaact gaccatctca tggttcgcca ttgttctgtt 60ggtcagtccc ctgatggcca tgtgggaact ggagaaagac gtctatgtgg tggaggtcga 120ttggacccca gatgctcctg gagagactgt gaacctgacc tgtgatacac ctgaggagga 180cgacattacg tggactagtg accagagaca tggggtgatt ggaagtggta agaccctgac 240aatcacagtc aaagaattcc tggatgcagg gcagtatacg tgtcacaaag gcggcgaaac 300gctctcccat tcccacttgc tccttcacaa gaaggagaat ggcatttggt ctacagagat 360cctcaagaac tttaagaaca agacctttct gaagtgcgaa gcacccaact atagcggtag 420gtttacttgc agttggctgg tacagcgaaa tatggacctc aaattcaaca tcaaaagctc 480tagcagctct cccgattctc gtgccgtgac ctgtgggatg gcctctcttt ccgccgagaa 540agtcaccctg gaccaaagag actacgagaa gtattcagtg agctgtcaag aagatgtgac 600atgcccaaca gctgaggaaa cccttcccat cgaattggct ctggaagcta gacagcagaa 660caagtacgaa aactactcca ctagcttctt catacgcgac atcatcaagc cagatcctcc 720gaagaatctg cagatgaagc ccctgaagaa ctctcaggtc gaagttagct gggagtatcc 780ggactcctgg tcaactccac actcctactt ttcactgaag ttcttcgtga ggatacagag 840gaagaaggag aaaatgaaag agactgagga gggatgtaat cagaaaggag cctttctcgt 900ggaaaagacc agtacagagg ttcaatgcaa aggcggcaat gtatgcgttc aagcgcagga 960tcggtactac aatagcagct gttccaagtg ggcatgcgtg ccttgtcggg tacgctcatg 1020atgcatctag ggcggccaat tccgcccctc tccctccccc ccccctaacg ttactggccg 1080aagccgcttg gaataaggcc ggtgtgcgtt tgtctatatg tgattttcca ccatattgcc 1140gtcttttggc aatgtgaggg cccggaaacc tggccctgtc ttcttgacga gcattcctag 1200gggtctttcc cctctcgcca aaggaatgca aggtctgttg aatgtcgtga aggaagcagt 1260tcctctggaa gcttcttgaa gacaaacaac gtctgtagcg accctttgca ggcagcggaa 1320ccccccacct ggcgacaggt gcctctgcgg ccaaaagcca cgtgtataag atacacctgc 1380aaaggcggca caaccccagt gccacgttgt gagttggata gttgtggaaa gagtcaaatg 1440gctctcctca agcgtattca acaaggggct gaaggatgcc cagaaggtac cccattgtat 1500gggatctgat ctggggcctc ggtgcacatg ctttacatgt gtttagtcga ggttaaaaaa 1560acgtctaggc cccccgaacc acggggacgt ggttttcctt tgaaaaacac gatgataagc 1620ttgccaatgg tgtcagtccc taccgcttct cctagtgcct catccagcag ctctcagtgt 1680cgtagcagca tgtgccaatc acggtacctg ttgttccttg ctactctcgc tctgctcaac 1740cacctgtctt tggcacgcgt gattccggtt tccggtcctg cgagatgcct gtcacagtcc 1800cggaatctgc tgaaaaccac cgatgacatg gtcaagacag ccagagagaa gctgaagcac 1860tacagttgca ctgcagagga tatagaccac gaagatatca cgcgagatca aaccagcaca 1920ctgaaaacat gcttgccact cgagttgcat aagaacgagt cttgtcttgc cactagagaa 1980acctctagca ccacaagggg cagttgtctc ccaccccaga aaacgtccct gatgatgaca 2040ctgtgtcttg gaagcatcta tgaggacctg aagatgtacc agacagagtt tcaggccata 2100aatgccgctc tgcagaacca caaccatcag cagattatcc tggacaaagg gatgcttgtc 2160gccattgacg agctgatgca aagcctgaat cacaacggcg aaactctgcg acagaaacca 2220cccgtaggag aagcagaccc ctatagggtg aagatgaagc tctgcatcct cctccatgca 2280ttctccacta gggtggtgac catcaatcgc gttatggggt atctgagttc cgcttgagct 2340agcgaattc 2349

Claims

1-17. (canceled)

18. A method for preventing or treating cancer, comprising the step of administering to a subject in need of the prevention or treatment for cancer a vaccinia virus comprising a polynucleotide encoding interleukin-7 (IL-7) and a polynucleotide encoding interleukin-12 (IL-12), wherein the vaccinia virus is deficient in the function of vaccinia virus growth factor (VGF) or deficient in the function of O1L.

19. The method according to claim 18, wherein the cancer is malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer or gastric cancer.

20. A method for preventing or treating cancer, comprising a step of administering to a subject in need of the prevention or treatment for cancer a vaccinia virus comprising a polynucleotide encoding IL-7 and a vaccinia virus comprising a polynucleotide encoding IL-12, wherein the vaccinia viruses are deficient in the function of vaccinia virus growth factor (VGF) or deficient in the function of O1L.

21. The method according to claim 20, wherein the cancer is malignant melanoma, lung adenocarcinoma, lung cancer, small cell lung cancer, lung squamous carcinoma, kidney cancer, bladder cancer, head and neck cancer, breast cancer, esophageal cancer, glioblastoma, neuroblastoma, myeloma, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, hepatocellular carcinoma, mesothelioma, cervical cancer or gastric cancer.

22-29. (canceled)