Pharmaceutical composition for cancer treatment containing miRNA

Abstract

The present invention aims to develop a pharmaceutical product with enhanced cancer therapeutic efficacy. The present invention provides a pharmaceutical composition for cancer treatment comprising a transcription product of a gene encoding a miRNA or a processed product thereof, wherein the miRNA is one or more miRNAs selected from miR-3140, miR-137, miR-631, and miR-657.

Description

Technical Field

[0001] The present invention relates to a pharmaceutical composition for treating cancer, comprising a transcription product of a gene encoding a specific miRNA or a processed product thereof. Background Art

[0002] MicroRNA (hereinafter referred to as miRNA) is a functional nucleic acid encoded in the genome and undergoes a multi-stage production process to ultimately become a small RNA of approximately 20 to 25 bases in length. MiRNAs are classified as functional ncRNAs (non-coding RNAs), and their important roles in various biological phenomena (e.g., gene expression control) are increasingly being elucidated. All known miRNAs, including human miRNAs, are registered in miRBase (see http: / / www.mirbase.org / ).

[0003] It has been shown that miRNAs are involved in the onset and progression of cancer, cardiovascular disease, neurodegenerative disease, mental illness, chronic inflammatory disease, etc. In particular, in recent years, it has been shown that miRNAs are deeply involved in cell carcinogenesis and cell aging.

[0004] For example, Patent Document 1 describes that miR-22 promotes cellular senescence and inhibits cancer invasion and / or metastasis. Furthermore, Patent Document 2 describes that a composition containing miR-34 can be used to treat cancer.

[0005] Prior art literature

[0006] Patent Literature

[0007] Patent Document 1: WO2011 / 078037

[0008] Patent Document 2: WO2008 / 137867 Summary of the Invention

[0009] The present inventors have conducted in-depth searches for miRNAs with cancer therapeutic effects among a large number of miRNAs.

[0010] As a result, the present inventors discovered a specific miRNA having a significantly higher cancer therapeutic effect than miRNAs described in the prior art, thereby completing the present invention.

[0011] That is, the present invention relates to a pharmaceutical composition for treating cancer, characterized in that it comprises a transcription product of a gene encoding miRNA or a processed product thereof.

[0012] The miRNA is one or more miRNAs selected from miR-3140, miR-137, miR-631 and miR-657.

[0013] In one embodiment of the present invention, the cancer is a solid cancer.

[0014] In one embodiment of the present invention, the solid cancer is colorectal cancer, pancreatic cancer, tongue cancer, mesothelioma, uterine sarcoma, osteosarcoma, breast cancer, lung cancer or head and neck cancer.

[0015] In one embodiment of the present invention, it is characterized in that the transcription product of the gene encoding the above-mentioned miRNA or its processed product is pri-miRNA, pre-miRNA, double-stranded mature miRNA, single-stranded mature miRNA expressed from the 5' end side of pre-miRNA, or single-stranded mature miRNA expressed from the 3' end side of pre-miRNA.

[0016] In one embodiment of the present invention, it is characterized in that the above-mentioned miRNA is:

[0017] (i) a mature miRNA consisting of the sequence set forth in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, or SEQ ID NO: 11;

[0018] (ii) a miRNA having a cancer therapeutic effect that has a substitution, addition, and / or deletion of 1 to 5 bases relative to a mature miRNA consisting of the sequence represented by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, or SEQ ID NO: 11; or

[0019] (iii) A miRNA that has a sequence identity of 80% or more to a mature miRNA consisting of the sequence represented by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, or SEQ ID NO: 11 and has a cancer therapeutic effect.

[0020] In one embodiment of the present invention, the miRNA is chemically modified.

[0021] In one embodiment of the present invention, it is characterized in that the above-mentioned chemical modification is one or more chemical modifications selected from LNAization, BNAization, ENAization, 2'-OMe modification, phosphorothioation, S-TuDization, morpholino modification, peptide addition, sugar chain addition, aptamer addition, hydrophobic molecule addition, polymer addition, and unmodified DNA addition.

[0022] In one embodiment of the present invention, the pharmaceutical composition further contains a nucleic acid transfection agent.

[0023] In one embodiment of the present invention, the transfection agent is a lipid-based transfection agent, a polymer-based transfection agent, a magnetic particle-based transfection agent, an exosome for nucleic acid delivery, or a viral protein for nucleic acid delivery.

[0024] One embodiment of the present invention is characterized in that the above-mentioned transfection agent is a transfection agent containing a peptide represented by the amino acid sequence of GGGGDD (G4D2), GGGGGGGDD (G6D2), GGGGGGGGGDD (G8D2), GGGGGGGGGGGDD (G10D2), AAAAAAD (A6D), AAAAAADD (A6D2), AAAAAAK (A6K), AAAAAAKK (A6K2), VVVVVVD (V6D), VVVVVVDD (V6D2), VVVVVVK (V6K), VVVVVVKK (V6K2), LLLLLLD (L6D), LLLLLLDD (L6D2), LLLLLLK (L6K) or LLLLLLKK (L6K2).

[0025] In one embodiment of the present invention, the pharmaceutical composition of the present invention is for topical administration.

[0026] In one embodiment of the present invention, the pharmaceutical composition of the present invention is used in combination with other anticancer agents.

[0027] In one embodiment of the present invention, it is characterized in that the above-mentioned other anticancer agents are one or more anticancer agents selected from alkylating agents, platinum preparations, metabolic antagonists, topoisomerase inhibitors, microtubule inhibitors, anticancer antibiotics, molecular targeted drugs, hormone preparations, immunomodulators, interferons, interleukins, plant-derived anticancer agents, and BRM preparations.

[0028] Another embodiment of the present invention is the use of a transcription product of a gene encoding miRNA or a processed product thereof in the manufacture of a pharmaceutical composition for treating cancer, characterized in that:

[0029] The miRNA is one or more miRNAs selected from miR-3140, miR-137, miR-631 and miR-657.

[0030] Another embodiment of the present invention relates to a method for treating cancer, characterized in that:

[0031] The method comprises the step of administering to a cancer patient a therapeutically effective amount of an anticancer pharmaceutical composition comprising a transcription product of a gene encoding miRNA or a processed product thereof,

[0032] The miRNA is one or more miRNAs selected from miR-3140, miR-137, miR-631 and miR-657.

[0033] Inventions obtained by arbitrarily combining one or more of the above-mentioned features of the present invention are also included in the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 The process of miRNA screening in this example is described.

[0035] Figure 2 The process of miRNA screening in this example is described.

[0036] Figure 3 Four miRNAs selected in miRNA screening that exhibit growth-suppressing effects on various cancer cells are shown.

[0037] Figure 4 The effects of the miRNA of the present invention on tongue cancer cell lines (HSC-4 cells, OSC19 cells) are shown.

[0038] Figure 5 The effect of the miRNA of the present invention on tongue cancer cell lines (SAS cells) is shown.

[0039] Figure 6 The effect of the miRNA of the present invention on a mesothelioma cell line (MSTO-211H cells) is shown.

[0040] Figure 7 The effect of the miRNA of the present invention on a mesothelioma cell line (EHMES-10 cells) is shown.

[0041] Figure 8 The effect of the miRNA of the present invention on a uterine sarcoma cell line (MES-SA cells) is shown.

[0042] Figure 9 The effect of the miRNA of the present invention on an osteosarcoma cell line (U2-OS cells) is shown.

[0043] Figure 10 The effect of the miRNA of the present invention on a cancer stem cell line (MDA-MB231-luc-D3H2LN cells) is shown.

[0044] Figure 11 The effect of the miRNA of the present invention on lung cancer cell line (A549 cells) is shown.

[0045] Figure 12The effects of the miRNA of the present invention on colorectal cancer cell lines (SW620 cells, SW480 cells, and HT29 cells) are shown.

[0046] Figure 13 This demonstrates the cancer therapeutic effect of the miRNA of the present invention in vivo.

[0047] Figure 14 The images show the results of tumor tissue imaging analysis 12, 19, 26, and 33 days after tumor cell transplantation.

[0048] Figure 15 Show the Figure 14 Figure 1 shows the quantitative results of the imaging analysis.

[0049] Figure 16 The results of comparison of tumor weight at the end point of the experiment are shown.

[0050] Figure 17 Shown are the imaging analysis results of tumor tissue after tumor cell transplantation.

[0051] Figure 18 The results of comparison of tumor weight at the end point of the experiment are shown.

[0052] Figure 19 The timetable for Experiment 7 is shown.

[0053] Figure 20 The imaging results when miR-3140-3p was administered once are shown.

[0054] Figure 21 The imaging results when miR-3140-3p was administered once are shown.

[0055] Figure 22 The figure shows the survival rate of mice after a single administration of miR-3140-3p.

[0056] Figure 23 The imaging results when miR-3140-3p was administered twice are shown.

[0057] Figure 24 The imaging results when miR-3140-3p was administered twice are shown.

[0058] Figure 25 The figure shows the survival rate of mice after two administrations of miR-3140-3p.

[0059] Figure 26 The imaging results when miR-3140-3p was administered three times are shown.

[0060] Figure 27 The imaging results when miR-3140-3p was administered three times are shown.

[0061] Figure 28 Shown are the survival rates of mice after three administrations of miR-3140-3p.

[0062] Figure 29 The results of Experiment 8 are shown.

[0063] Figure 30 Comparison of the tumor suppressive effects of miR-3140-3p and cisplatin is shown.

[0064] Figure 31 Comparison of the tumor suppressive effects of miR-3140-3p and cisplatin is shown.

[0065] Figure 32 Comparison of the tumor suppressive effects of miR-3140-3p and cisplatin is shown.

[0066] Figure 33 Comparison of survival rates between the miR-3140-3p-administered group and the cisplatin-administered group is shown. DETAILED DESCRIPTION

[0067] The present invention relates to a pharmaceutical composition for cancer treatment containing a transcription product of a gene encoding a miRNA (micro-RNA) or a processed product thereof. Generally, miRNAs are biosynthesized through a continuous process. The primary transcription product of a miRNA-encoding gene is called a primary miRNA transcript (pri-miRNA), which typically has a stem-loop hairpin structure. The pri-miRNA is cleaved by the microprocessor complex and converted to a hairpin form by the action of Drosha, an RNase III enzyme, to produce a precursor miRNA (pre-miRNA), an intermediate precursor of approximately 70 bases. The pre-miRNA is then transported from the cell nucleus to the cytoplasm. In the cytoplasm, it is further cleaved by Dicer, another RNase III enzyme, to produce a double-stranded mature miRNA. Generally, the double-stranded sequence expressed from the 5' end of the precursor is labeled "-5p," and the sequence expressed from the 3' end is labeled "-3p," and is described as "hsa-miR-21-5p" or "hsa-miR-21-3p." In principle, known miRNAs have already been registered in miRBase (http: / / www.mirbase.org / ).

[0068] It should be noted that sometimes only one strand of the mature miRNA exerts the desired effect, sometimes both strands exert the desired effect, and sometimes the desired effect is exerted in a double-stranded state. In addition, the desired effect may be exerted in the form of pri-miRNA or pre-miRNA.

[0069] The nucleic acid contained in the composition of the present invention can be a transcription product of a gene encoding one or more miRNAs selected from miR-3140, miR-137, miR-631 and miR-657, or a processed product thereof, and can also be a variant or modified form that retains the function of the nucleic acid.

[0070] The sequence of the transcription product of the gene encoding miR-3140 or its processed product used in one embodiment of the present invention is shown below.

[0071] [Table 1]

[0072]

[0073] In addition, the sequence of the intron region encoding the pri-miRNA of miR-3140 is shown in SEQ ID NO: 4.

[0074] The sequence of the transcription product of the gene encoding miR-137 or its processed product used in one embodiment of the present invention is as follows.

[0075] [Table 2]

[0076]

[0077] In addition, the sequence of the intron region encoding the pri-miRNA of miR-137 is shown in SEQ ID NO: 7.

[0078] The sequence of the transcription product of the gene encoding miR-631 or its processed product used in one embodiment of the present invention is shown below.

[0079] [Table 3]

[0080]

[0081] In addition, the sequence of the intron region encoding the pri-miRNA of miR-631 is shown in SEQ ID NO: 10.

[0082] The sequence of the transcription product of the gene encoding miR-657 or its processed product used in one embodiment of the present invention is shown below.

[0083] [Table 4]

[0084]

[0085] In addition, the sequence of the intron region encoding the pri-miRNA of miR-657 is shown in SEQ ID NO: 13.

[0086] The nucleic acids contained in the compositions of the present invention may, for example, have 1, 2, 3, 4, or 5 base substitutions, additions, and / or deletions relative to a mature miRNA consisting of the sequence represented by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, or SEQ ID NO: 11, and may have the effect of inhibiting cancer cell growth. The base substitutions in the mature miRNA may, for example, be conservative substitutions known in the art for RNA.

[0087] In addition, the nucleic acid contained in the composition of the present invention can be, for example, a nucleic acid having a sequence homology (or sequence identity) of 80% or more (preferably 85% or more, 90% or more, 95% or more) with respect to a mature miRNA consisting of a sequence represented by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8 or SEQ ID NO: 11 and having an effect of inhibiting the growth of cancer cells.

[0088] Mature miRNAs consisting of the sequences represented by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, or SEQ ID NO: 11 can be easily produced using RNA synthesis equipment commonly used in the art. It is also easy to produce nucleic acids in which specific bases are substituted, added, and / or deleted. Furthermore, many companies offer commissioned nucleic acid synthesis, making it easy for such companies to obtain RNAs of the desired sequence. Therefore, anyone skilled in the art can investigate the properties or functions of variants or modifications of mature miRNAs consisting of the sequences represented by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 8, or SEQ ID NO: 11 according to conventional methods without incurring undue burden.

[0089] In addition, in order to improve the stability, specificity etc. of RNA, the nucleic acid contained in the composition of the present invention can implement chemical modification well known in the art.The chemical modification that the present invention can use can be, for example, LNA (locked nucleic acid, LockedNucleic Acid) ization, BNA (bridged nucleic acid, Bridged Nucleic Acid) ization, ENA (2'-O, 4'-C- ethylene bridged nucleic acid, 2'-O, 4'-C-Ethylene-bridged Nucleic Acids) ization, 2'-OMe modification, thiophosphorylation (S), S-TuD (synthesis of Tough Decoy) ization, morpholino modification, peptide addition, sugar chain addition, aptamer addition, cholesterol and other hydrophobic molecules addition, PEG and other macromolecules add or non-modified DNA addition.These chemical modifications can be carried out by methods well known in the art.

[0090] The present invention can be used to treat various cancers, for example, solid cancers. More preferably, the subject of the present invention can be colorectal cancer, pancreatic cancer, tongue cancer, mesothelioma, uterine sarcoma, osteosarcoma, breast cancer, lung cancer or head and neck cancer.

[0091] In order to appropriately introduce the present invention into cancer cells, the composition of the present invention may further contain a nucleic acid transfection agent. Examples of nucleic acid transfection agents that can be used in the present invention include lipid-based transfection agents, polymer-based transfection agents, magnetic particle-based transfection agents, exosomes for nucleic acid delivery, or viral proteins for nucleic acid delivery.

[0092] Examples of lipid-based transfection agents include cationic lipids. Cationic lipids are taken up by cells via endocytosis via nucleic acid-cationic lipid complexes and released into the cytoplasm, thereby introducing nucleic acids into cells (lipofection). Specifically, various commercially available lipofection reagents can be used.

[0093] As the example of polymer-based transfection agents, for example, cationic polymers can be enumerated. Cationic polymers form nucleic acid-polymer complexes when in contact with nucleic acids, and the complexes are attached to cell membranes via electrostatic interactions and are taken up by cells via endocytosis. Specifically, cationic peptides and their derivatives (for example, polylysine, polyornithine), straight or branched synthetic polymers (for example, polybrene, polyethyleneimine), the introduction molecules of polysaccharide matrices (for example, cyclodextrin, chitosan), natural polymers (for example, histones, collagen) and active and inactive dendrimers etc. can be used. In addition, the transfection agents of the block copolymers forming micellar nanoparticles, the transfection agents of carbon nanohorns etc., the transfection agents used in so-called nano DDS can also be used for the present invention.

[0094] Examples of magnetic particle-based transfection agents include those using magnetic particles coated with cationic molecules. Magnetic particle-based transfection agents achieve transfection by binding nucleic acids to the surface of magnetic particles, which are then introduced into cells under magnetic influence. Specifically, various commercially available magnetic particles for transfection can be used.

[0095] Furthermore, transfection agents using generally available exosome nucleic acids and transfection agents using viral proteins such as adenovirus can also be used in the present invention.

[0096] In addition, in the present invention, a polypeptide containing GGGGDD (G4D2) (SEQ ID NO: 14), GGGGGGDD (G6D2) (SEQ ID NO: 15), GGGGGGGGGDD (G8D2) (SEQ ID NO: 16), GGGGGGGGGGDD (G10D2) (SEQ ID NO: 17), AAAAAAD (A6D) (SEQ ID NO: 18), AAAAAADD (A6D2) (SEQ ID NO: 19), AAAAAAK (A6K) (SEQ ID NO: 20), AAAAAAKK (A6K2) (SEQ ID NO: 21), VVVVVVD (V6D) can be used. (SEQ ID NO: 22), VVVVVVDD(V6D2) (SEQ ID NO: 23), VVVVVVK(V6K) (SEQ ID NO: 24), VVVVVVKK(V6K2) (SEQ ID NO: 25), LLLLLLD(L6D) (SEQ ID NO: 26), LLLLLLDD(L6D2) (SEQ ID NO: 27), LLLLLLK(L6K) (SEQ ID NO: 28), or LLLLLLKK(L6K2) (SEQ ID NO: 29) can be particularly preferably used as a transfection agent for a peptide. The effects of these peptides as transfection agents are disclosed, for example, in WO2010 / 024262.

[0097] The pharmaceutical composition for cancer treatment of the present invention can be used in combination with other anticancer agents known in the art. The other anticancer agents used in combination are not limited; for example, one or more anticancer agents selected from alkylating agents, platinum preparations, metabolic antagonists, topoisomerase inhibitors, microtubule inhibitors, anticancer antibiotics, molecular targeted drugs, hormone preparations, immunomodulators, interferons, interleukins, plant-derived anticancer agents, and BRM preparations can be used.

[0098] There is no limitation on the combined use of the pharmaceutical composition for treating cancer of the present invention and other anticancer agents known in the art, and those skilled in the art (e.g., physicians) can implement the method in various ways according to the type of cancer being treated, the stage of treatment, etc. The pharmaceutical composition for treating cancer of the present invention and other anticancer agents can be administered to the subject simultaneously or at different times. In addition, the pharmaceutical composition for treating cancer of the present invention and other anticancer agents can also be prepared as a combination containing the pharmaceutical composition for treating cancer of the present invention and other anticancer agents, and administered to the subject. In addition, the pharmaceutical composition for treating cancer of the present invention and other anticancer agents can also be prepared as a kit containing the pharmaceutical composition for treating cancer of the present invention and other anticancer agents, respectively.

[0099] As a mode of simultaneously administering the pharmaceutical composition for cancer treatment of the present invention and other anticancer agents, for example, a combination formulation containing the pharmaceutical composition for cancer treatment of the present invention and other anticancer agents may be administered to a subject.

[0100] In the present invention, as a method of administering the pharmaceutical composition for cancer treatment of the present invention and other anticancer agents at different times, for example, a method of administering the pharmaceutical composition for cancer treatment of the present invention and other anticancer agents at staggered times can be used. In addition, for example, a method of administering the pharmaceutical composition for cancer treatment of the present invention and other anticancer agents by different administration routes can be used.

[0101] The administration route of the pharmaceutical composition for cancer treatment of the present invention is not limited and may be systemic or topical. Examples of administration routes include oral administration including sublingual administration, inhalation administration, direct administration to target tissues via catheter or injection, intravenous administration including intravenous drips, transdermal administration using patches, suppositories, and parenteral administration such as forced enteral nutrition via nasogastric tube, nasointestinal tube, gastric fistula, or intestinal fistula.

[0102] The dosage form of the pharmaceutical composition for cancer treatment of the present invention can be appropriately determined according to the above-mentioned administration route and is not limited thereto. Examples include injections, drips, tablets, capsules, fine granules, powders, liquids, aqueous solutions dissolved in syrups, patches, suppositories, and the like.

[0103] The subjects to whom the pharmaceutical composition of the present invention is administered are not limited, and for example, the present invention can be used on mammals (humans, pigs, cows, monkeys, baboons, dogs, cats, rats, mice, etc.) However, in preferred cases, humans can be excluded from the subjects.

[0104] The method of administration of the pharmaceutical composition of the present invention to a subject (administration route, dosage, number of administrations per day, timing of administration, etc.) is not limited and can be appropriately determined by a person skilled in the art (e.g., a physician) based on the subject's health condition, the severity of the disease, the type of concomitant medication, etc.

[0105] Unless otherwise defined, the terms used in this specification are for describing specific embodiments and are not intended to limit the invention.

[0106] In addition, unless the context clearly indicates otherwise, the term "comprising" used in this specification is intended to indicate the presence of stated matters (components, steps, elements, numbers, etc.) and does not exclude the presence of other matters (components, steps, elements, numbers, etc.).

[0107] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by those skilled in the art to which the present invention belongs. Unless otherwise explicitly defined, the terms used herein should be interpreted as having the same meaning as in this document and in the prior art and should not be interpreted as idealized or overly formalized.

[0108] Hereinafter, the present invention will be described in detail with reference to Examples. However, the present invention can be implemented in various forms and should not be construed as being limited to the Examples described herein.

[0109] Example

[0110] Experiment 1: Screening of miRNAs with high cellular senescence-inducing ability

[0111] (1) Transfection of TIG-3 cells with total miRNA Figure 1 )

[0112] A total of 2028 miRNAs (mirVana; Ambion) were transfected into TIG-3 cells (human fibroblasts) using an automatic pipette Bravo (Agilent). Transfection was performed according to the following steps.

[0113] 1: Add 0.35 μL of RNAiMAX (Invitrogen) to 70 μL of serum-free medium (SFM).

[0114] 2: Use Bravo to add the solution in 1 to a 96-well plate (μ-plate; ibidi).

[0115] 3: Use Bravo to add 0.7 μL of miRNA (stock concentration 2 μM) to 2 and mix by pipetting.

[0116] 4: Incubate at room temperature for 20 minutes.

[0117] 5: Use Bravo to dilute to 3.5×10 4 cells / mL of cell suspension were aliquoted in 70 μL.

[0118] 6: Incubate at 37°C and 5% CO2.

[0119] (2-1) Staining of transfected cells

[0120] The day of transfection was designated as Day 0, and staining was performed 5 days later to evaluate the cell number and cell size. The procedure is shown below.

[0121] 1: Wash twice with PBS(-).

[0122] 2: Add 3.7% formalin solution and incubate at room temperature for 10 minutes to fix the cells.

[0123] 3: Wash twice with PBS(-).

[0124] 4: Add staining solution and incubate at room temperature for 30 minutes to stain.

[0125] 5: Wash three times with PBS(-).

[0126] 6: After staining, the plate was photographed in its entire field of view using the automatic photographing device Operetta (Perkin Elmer).

[0127] 7: The captured photos were quantitatively analyzed using the image analysis software Columbus (Perkin Elmer).

[0128] [Table 5]

[0129] Table 5: Composition of staining solution

[0130]

[0131] (2-2) SA-β-galactosidase analysis of transfected cells

[0132] The day of transfection was designated as day 0, and SA-β-galactosidase analysis was performed on day 7.

[0133] The operation steps are shown below.

[0134] 1: Wash twice with PBS(-).

[0135] 2: Add 2% formalin solution and incubate at room temperature for 5 minutes to fix the cells.

[0136] 3: Wash twice with PBS(-).

[0137] 4: Prepare β-Gal staining solution when using and add it to the wells.

[0138] 5: Incubate at 37°C for 12-16 hours.

[0139] 6: After staining, the plate was photographed using an automatic photographing device Opera (Perkin Elmer).

[0140] [Table 6]

[0141] Table 6: Composition of β-Gal staining solution

[0142]

[0143] *1: Prepared to pH 6

[0144] *2: X-gal (5-bromo-4-chloro-3-indole-β-D-galactopyranoside: Wako) was prepared with N,N-dimethylformamide at the time of use.

[0145] (3) Analysis of screening results ( Figure 2 )

[0146] The obtained cell number and cell size values ​​were scored using the values ​​of random sequence miRNA as a negative control and miR-34a-5p as a positive control. The scoring method is shown below.

[0147] In each board,

[0148] 1: Subtract the positive control value from the negative control value.

[0149] 2: The value of each miRNA was subtracted from the value of the negative control.

[0150] 3: Divide the value of 2 by the value of 1 to obtain the score.

[0151] 4: Take the score value of cell number on the horizontal axis and the score value of cell size on the vertical axis and draw a scatter plot.

[0152] 5: miRNAs showing a high score compared to at least one of the scores of miR-22-3p and miR-22-5p were identified as senescence-inducing miRNA candidates, and 579 miRNAs were identified.

[0153] 6: Among 579 candidates, 349 miRNAs that induce activation of β-galactosidase, a cell senescence marker, were identified as senescence-inducing miRNAs.

[0154] Experiment 2: Further screening using cancer cell lines

[0155] The 349 senescence-inducing miRNAs (mirVana; Ambion) screened were transfected into various cancer cell lines (colorectal cancer cell line HCT116 (p53 wild-type and p53-deficient), pancreatic cancer cell lines BxPC-3 and CFPAC-1, and tongue cancer cell line HSC-4) using an automatic pipette Bravo (Agilent).

[0156] Transfection was performed according to the following steps.

[0157] 1: Add 0.35 μL of RNAiMAX (Invitrogen) to 70 μL of serum-free medium (SFM).

[0158] 2: Use Bravo to add the solution in 1 to a 96-well plate (μ-plate; ibidi).

[0159] 3: Use Bravo to add 0.7 μL of miRNA (stock concentration 200 nM) to 2 and mix by pipetting.

[0160] 4: Incubate at room temperature for 20 minutes.

[0161] 5: Use Bravo to dilute to 3.5×10 4 cells / mL of cell suspension were aliquoted in 70 μL.

[0162] 6: Incubate at 37°C and 5% CO2.

[0163] The day of transfection was defined as day 0, and the cell survival rate was evaluated using PrestoBlue (Invitrogen) on day 5. The procedure is shown below.

[0164] 1. Replace the culture medium with 20-fold diluted PrestoBlue and incubate at 37°C for 1 hour.

[0165] 2. Fluorescence values ​​(Ex / Em=560 nm / 590 nm) were measured using Enspire (Perkin Elmer).

[0166] 3. The fluorescence value obtained from the wells containing only the reagent was used as the background to determine the cell survival rate.

[0167] The above steps were performed on cancer cell lines (colorectal cancer cell line HCT116 (p53 wild type and p53 deficiency), pancreatic cancer cell lines BxPC-3 and CFPAC-1, and tongue cancer cell line HSC-4) to select miRNAs that significantly inhibit cell proliferation compared with miR-34a-5p.

[0168] The miRNAs that significantly inhibited cell proliferation compared to miR-34-5p were selected in all cell lines. As a result, four miRNAs (miR-137-3p, miR-631-5p, miR-657-3p, miR-3140-3p) were found. Figure 3 ).

[0169] Experiment 3: Confirmation of cell proliferation inhibitory effects using various cancer cell lines

[0170] (1) Tongue cancer cell lines (HSC-4, OSC-19) Figure 4 )

[0171] Four miRNAs (miR-137-3p, miR-631-5p, miR-657-3p, and miR-3140-3p) were transfected into tongue cancer cell lines (HSC-4 and OSC-19) and cell proliferation was observed. Transfection was performed according to the following steps.

[0172] 1: Add 500 μL of serum-free medium (SFM) and 5 μL of RNAiMAX (Invitrogen) to a 35 mm culture dish.

[0173] 2: Add 1 μL of nucleic acid (control, miR-137-3p, miR-631-5p, miR-657-3p, miR-3140-3p, and an equal amount of a mixture of four miRNAs) to the solution in step 1. (Final concentration: 10 nM)

[0174] 3: Incubate at room temperature for 20 minutes.

[0175] 4: Dilute to 6.7×10 4 1.5 mL of cell suspension at 5 cells / mL was added to each 35 mm culture dish.

[0176] 5: Incubate at 37°C and 5% CO2.

[0177] 6: Count cells 5 days after transfection.

[0178] like Figure 4 As shown, the four miRNAs showed cell proliferation inhibitory effects in any tongue cancer cell line.

[0179] (2) Tongue cancer cell line (SAS) Figure 5 )

[0180] Four miRNAs (miR-137-3p, miR-631-5p, miR-657-3p, and miR-3140-3p) were transfected into a tongue cancer cell line (SAS) and cell proliferation was observed. Transfection was performed according to the following steps.

[0181] 1: Add 500 μL of serum-free medium (SFM) and 5 μL of RNAiMAX (Invitrogen) to a 35 mm culture dish.

[0182] 2: Add 4 μL of each miRNA solution (see Table 7) to the solution in 1 (final concentration 10 nM)

[0183] 3: Incubate at room temperature for 20 minutes.

[0184] 4: Dilute to 6.7×10 4 1.5 mL of cell suspension at 5 cells / mL was added to each 35 mm culture dish.

[0185] 5: Incubate at 37°C and 5% CO2.

[0186] 6: Repeat steps 1 to 3 2 days after transfection.

[0187] 7: Add the solutions prepared in step 6 to the culture dishes in step 5.

[0188] 8: Cell counts were performed 7 days after the initial transfection.

[0189] according to Figure 5 It can be seen that all four miRNAs showed cell proliferation inhibitory effects on the tongue cancer cell line SAS.

[0190] [Table 7]

[0191] Table 7: miRNA dosage

[0192]

[0193] (3) Malignant pleural mesothelioma cell lines, uterine sarcoma cell lines, osteosarcoma cell lines ( Figures 6 to 9 )

[0194] Among the four miRNAs described above, miR-3140-3p, which exhibits a particularly strong inhibitory effect on cell proliferation, was transfected into malignant pleural mesothelioma cell lines (MSTO-211H and EHMES-10), a uterine sarcoma cell line (MES-SA), and an osteosarcoma cell line (U2-OS), and cell proliferation was observed. For comparison, miR-22-3p and miR-34a-5p, which have demonstrated inhibitory effects on cell proliferation in prior studies, were used. Transfection was performed according to the following procedures.

[0195] 1: Add 500 μL of serum-free medium (SFM) and 5 μL of RNAiMAX (Invitrogen) to a 35 mm culture dish.

[0196] 2: Add 1 μL of miR-control or miR-3140-3p, miR-22-3p, miR-34a-5p (stock concentration 20 μM) to the solution in 1 (final concentration 10 nM)

[0197] 3: Incubate at room temperature for 20 minutes.

[0198] 4: Dilute to 6.7×10 4 1.5 mL of cell suspension at 5 cells / mL was added to each 35 mm culture dish.

[0199] 5: Incubate at 37°C and 5% CO2.

[0200] 6: Count cells 4 days after transfection.

[0201] according to Figures 6 to 9 It was found that miR-3140-3p exhibited a significantly higher cell proliferation inhibitory effect in all cell lines compared to miR-22-3p and miR-34a-5p, which are conventional technologies.

[0202] (4) Breast cancer stem cell line (MDA-MB231-luc-D3H2LN cells) Figure 10 )

[0203] MiR-3140-3p was transfected into a highly metastatic breast cancer cell line (MDA-MB231-luc-D3H2LN) and cell proliferation was observed. For comparison, miR-22-3p and miR-34a-5p, which have been shown to inhibit cell proliferation in previous studies, were used. Transfection was performed according to the following procedures.

[0204] 1: Add 500 μL of serum-free medium (SFM) and 5 μL of RNAiMAX (Invitrogen) to a 35 mm culture dish.

[0205] 2: Add 12.5 μL of miR-control or miR-3140-3p, miR-22-3p, miR-34a-5p (stock concentration 2 μM) to the solution in 1 (final concentration 12.5 nM)

[0206] 3: Incubate at room temperature for 20 minutes.

[0207] 4: Add 1.5 mL of the cell suspension diluted to 6.7×104 cells / mL to each 35 mm culture dish.

[0208] 5: Incubate at 37°C and 5% CO2.

[0209] 6: Count cells 4 days after transfection.

[0210] In addition, the expression of Annexin V, an apoptosis marker, in breast cancer cells transfected with miR-3140-3p was analyzed according to the following procedure.

[0211] 1: Following the same steps as above, transfection of miR-3140-3p was performed.

[0212] 2: Six days after transfection, the cells and supernatant were recovered.

[0213] 3: Prepare samples for FACS according to the protocol of the Annexin V assay kit.

[0214] 4: Cells stained with Annexin V-FITC were stained using an antibody against CD44 (eBioScience), a cancer stem cell marker.

[0215] 5: The prepared samples were analyzed using a cell sorter (SONY).

[0216] according to Figure 10 As can be seen from the above paragraph, miR-3140-3p exhibits an extremely high cell proliferation inhibitory effect on breast cancer stem cell lines (MDA-MB231-luc-D3H2LN cells).

[0217] In addition, according to Figure 10 The lower part shows that annexin V, an apoptosis marker, was highly positive (96.97%) in breast cancer stem cells 6 days after transfection with miR-3140-3p. This indicates that miR-3140-3p significantly induces apoptosis in cancer stem cells.

[0218] (5) Lung cancer cell line (A549) Figure 11 )

[0219] miR-3140-3p was transfected into lung cancer cell line A549, and cell proliferation was observed. For comparison, miR-22-3p and miR-34a-5p, which have been shown to inhibit cell proliferation in previous studies, were used. Transfection was performed according to the following procedure.

[0220] 1: Add 500 μL of serum-free medium (SFM) and 5 μL of RNAiMAX (Invitrogen) to a 35 mm culture dish.

[0221] 2: Add 1 μL of miR-control or miR-3140-3p, miR-22-3p, miR-34a-5p (stock concentration 20 μM) to the solution in 1 (final concentration 10.0 nM)

[0222] 3: Incubate at room temperature for 20 minutes.

[0223] 4: Dilute to 6.7×10 4 1.5 mL of cell suspension at 5 cells / mL was added to each 35 mm culture dish.

[0224] 5: Incubate at 37°C and 5% CO2.

[0225] 6: Cell counts were performed 6 days after transfection.

[0226] according to Figure 11 It can be seen that miR-3140-3p exhibits an extremely high cell proliferation inhibitory effect on lung cancer cell line (A549).

[0227] (6) Colorectal cancer cell lines (SW620, SW480, HT29) Figure 12 )

[0228] MiR-3140-3p was transfected into colorectal cancer cell lines (SW620, SW480, and HT29) and cell proliferation was observed. Transfection was performed according to the following steps.

[0229] 1: Add 500 μL of serum-free medium (SFM) and 5 μL of RNAiMAX (Invitrogen) to a 35 mm culture dish.

[0230] 2: Add 12.5 μL of miR-control or miR-3140-3p, miR-22-3p, miR-34a-5p (stock concentration 2 μM) to the solution in 1 (final concentration 10.0 nM)

[0231] 3: Incubate at room temperature for 20 minutes.

[0232] 4: Add 1.5 mL of the cell suspension diluted to 6.7×104 cells / mL to each 35 mm culture dish.

[0233] 5: Incubate at 37°C and 5% CO2.

[0234] 6: Count cells 7 days after transfection.

[0235] The results are shown in Figure 12 The number of cells transfected with the control was set as 100%, and the survival rate of cells transfected with miR-3140-3p was expressed as %. Figure 12 It can be seen that miR-3140-3p exhibits an extremely high cell proliferation inhibitory effect on any colorectal cancer cell line.

[0236] Experiment 4. Anti-tumor effect of the miRNA of the present invention in vivo (malignant pleural mesothelioma cells) ( Figure 13 )

[0237] In order to confirm the in vivo anti-tumor effect of the miRNA of the present invention, an experiment was conducted using experimental animals transplanted with malignant pleural mesothelioma cells.

[0238] (1) Cell preparation

[0239] Malignant pleural mesothelioma MSTO-211H cells were used.

[0240] 1: Wash the cells on the culture dish twice with PBS(-).

[0241] 2: Use trypsin to detach the cells.

[0242] 3: Suspend in culture medium and count cells.

[0243] 4: Centrifuge and precipitate at 1000 rpm for 3 min.

[0244] 5: Cells are grown to reach 2.0 × 10 7 cells / mL and resuspended in PBS(-).

[0245] (2) Cell transplantation in mice

[0246] Six-week-old CB-17 / Icr-scid / scid Jcl mice (SCID mice) were used. 100 μL of the prepared cell suspension was administered subcutaneously to the SCID mice to fix the cells.

[0247] (3) miRNA administration

[0248] A negative control was used as a control sequence, and miR-3140-3p was used as the miRNA of the present invention. A6K (3D Matrix) was used as a nucleic acid delivery agent. The administration of miRNA to mice was carried out according to the following procedure.

[0249] 1: Dilute 100 μM nucleic acid (miRNA) to 71.4 μM using 10% saline and sterile water.

[0250] 2: Ultrasonicate the 1% A6K solution for 5 minutes before use.

[0251] 3: Mix the diluted nucleic acid and 1% A6K solution in a 1:1 ratio to prepare the administration nucleic acid.

[0252] 4: 50 μL of the nucleic acid was administered subcutaneously (tumor site) to SCID mice.

[0253] (5) Evaluation

[0254] The evaluation of the experimental results was performed according to the following steps.

[0255] 1: Administer nucleic acid every 1 or 2 days starting from 4 days after transplantation.

[0256] 2: A total of 13 administrations were performed, and the end point of the experiment was 34 days after transplantation.

[0257] 3: The mice were dissected, the subcutaneous tumors were removed, and their weights were measured.

[0258] The experimental results are shown in Figure 13 (n=3). Figure 13 It was found that the tumor weight in mice into which miR-3140-3p was introduced into the tumor site was significantly lower than that in the control group.

[0259] Experiment 5. In vivo anti-tumor effect of the miRNA of the present invention (malignant pleural mesothelioma cells) ( Figures 14-16)

[0260] (1) Cell preparation

[0261] Malignant pleural mesothelioma EHMES-10 cells were used.

[0262] 1: Wash the cells on the culture dish twice with PBS(-).

[0263] 2: Use trypsin to detach the cells.

[0264] 3: Suspend in culture medium and count cells.

[0265] 4: Centrifuge and precipitate at 1000 rpm for 3 min.

[0266] 5: Cells are grown to reach 2.0 × 10 7 cells / mL and resuspended in PBS(-).

[0267] (2) Cell transplantation in mice

[0268] Six-week-old CB-17 / Icr-scid / scid Jcl mice (SCID mice) were used. 100 μL of the prepared cell suspension was administered subcutaneously to the SCID mice to fix the cells.

[0269] (3) miRNA administration

[0270] A negative control and miR-3140-3p, the miRNA of the present invention, were used as control sequences. A6K (3D Matrix) was used as a nucleic acid delivery agent. Administration of miRNA to mice was carried out according to the following procedure.

[0271] 1: Dilute 100 μM of nucleic acid (miRNA) to 71.4 μM using 10% physiological saline and sterile water.

[0272] 2: Ultrasonicate the 1% A6K solution for 5 minutes before use.

[0273] 3: Mix the diluted nucleic acid and 1% A6K solution in a 1:1 ratio to prepare the administration nucleic acid.

[0274] 4: 50 μL of each administered nucleic acid was administered subcutaneously (tumor site) to SCID mice.

[0275] (5) Evaluation

[0276] The evaluation of the experimental results was performed according to the following steps.

[0277] 1: Nucleic acid is administered every 1 or 2 days starting from 2 days after transplantation.

[0278] 2: A total of 13 administrations were performed, and the 33rd day after transplantation was set as the end point of the experiment.

[0279] 3: 12, 19, 26, and 33 days after transplantation, fluorescein was administered into the peritoneal cavity and imaging was performed to track the size of the tumor.

[0280] 4: At the end of the experiment, the mice were dissected, the subcutaneous tumors were removed, and their weights were measured.

[0281] The imaging analysis results of tumor tissues 12, 19, 26, and 33 days after tumor cell transplantation are shown in Figure 14 and Figure 15 .according to Figure 14 and Figure 15 It was found that in mice that had miR-3140-3p introduced into the tumor, tumor growth was suppressed compared to the control group. Figure 16 The same results are shown in .

[0282] Experiment 6. In vivo anti-tumor effect of the miRNA of the present invention (tongue cancer cells) ( Figure 17 、 Figure 18 )

[0283] (1) Cell preparation

[0284] Tongue cancer cell line HSC-4 cells were used.

[0285] 1: Wash the cells on the culture dish twice with PBS(-).

[0286] 2: Use trypsin to detach the cells.

[0287] 3: Suspend in culture medium and count cells.

[0288] 4: Centrifuge and precipitate at 1000 rpm for 3 min.

[0289] 5: Cells are grown to reach 2.0 × 10 7 cells / mL and resuspended in PBS(-).

[0290] (2) Cell transplantation in mice

[0291] Six-week-old CB-17 / Icr-scid / scid Jcl mice (SCID mice) were used. 100 μL of the prepared cell suspension was administered subcutaneously to the SCID mice to fix the cells.

[0292] (3) miRNA administration

[0293] A negative control was used as a control sequence, and miR-3140-3p, miR-137, miR-631, and miR-657, the miRNAs of the present invention, were used. A6K (3D Matrix) was used as a nucleic acid delivery agent. Administration of miRNA to mice was performed according to the following procedure.

[0294] 1: Dilute 100 μM of nucleic acid (miRNA) to 71.4 μM using 10% physiological saline and sterile water.

[0295] 2: Ultrasonicate the 1% A6K solution for 5 minutes before use.

[0296] 3: Mix the diluted nucleic acid and 1% A6K solution in a 1:1 ratio to prepare the administration nucleic acid.

[0297] 4: 50 μL of the administered nucleic acid was administered subcutaneously (tumor site) to SCID mice.

[0298] (5) Evaluation

[0299] The evaluation of the experimental results was performed according to the following steps.

[0300] 1: Administer nucleic acid every 1 or 2 days starting from 3 days after transplantation.

[0301] 2: A total of 11 administrations were performed, and the end point of the experiment was 28 days after transplantation.

[0302] 3: 7, 14, 21, and 28 days after transplantation, fluorescein was administered into the peritoneal cavity and imaging was performed to track the size of the tumor.

[0303] 4: At the end of the experiment, the mice were dissected, the subcutaneous tumors were removed, and their weights were measured.

[0304] The imaging analysis results of tumor tissue after tumor cell transplantation are shown in Figure 17 .according to Figure 17 It was found that in mice into which the miRNA of the present invention was introduced into the tumor, the growth of the tumor was suppressed compared with the control group. Figure 18 The same results are also shown in .

[0305] The above results indicate that the miRNA of the present invention also has a very high anti-tumor effect in vivo.

[0306] Experiment 7. In vivo anti-tumor effect of the miRNA of the present invention (malignant pleural mesothelioma cells) ( Figures 19-28 )

[0307] The tumor suppressive effect of miR-3140-3p in vivo was studied using an intrathoracic orthotopic transplantation model mouse model.

[0308] Six-week-old male mice (CB-17 / Icr-scid / scidJcl) were used, and tumor cells used were the malignant pleural mesothelioma cell line EHMES-10 expressing the luciferase gene.

[0309] The experimental procedures are shown below.

[0310] 1: Administer 0.1 mL of a mixed anesthetic of medetomidine hydrochloride, midazolam, and butorphanol tartrate per 10 g of body weight into the mouse's peritoneal cavity.

[0311] 2: After anesthesia, shave the mouse's chest and cut the epidermis with scissors.

[0312] 3: Use a 27G insulin syringe to transplant 100 μL of tumor cells (3×10 7 cells / mL).

[0313] 4: Three days after transplantation, tumor cells were imaged using an in vivo three-dimensional multimodal imaging system (IVIS SpectrumCT in vivo Imaging System).

[0314] 5: After imaging, mice with successful transplantation were divided into groups.

[0315] 6: Anesthetize the mouse by intraperitoneally administering 0.1 mL of a mixed anesthetic of medetomidine hydrochloride, midazolam, and butorphanol tartrate per 10 g of body weight.

[0316] 7: After anesthesia, 100 μL of miRNA / A6K mixture was administered into the chest cavity of the mouse.

[0317] 8: Starting from the initial imaging, imaging was performed every week to observe the tumor growth.

[0318] 9: Record the time of death of mice and calculate the survival rate of mice.

[0319] The time of drug administration and imaging is shown in Figure 19 A mixed anesthetic of medetomidine hydrochloride, midazolam, and butorphanol tartrate was prepared as shown in Table 8. A miRNA / A6K mixture was prepared as shown in Table 9. In addition, the control group was administered with the RNA shown in Table 10 instead of the miRNA of the present invention.

[0320] In order to improve expression efficiency, miRNA is administered in a double-stranded form combined with a complementary strand containing a partial mismatch.

[0321] [Table 8]

[0322] Table 8 Preparation of mixed anesthetics

[0323]

[0324] [Table 9]

[0325] Table 9 Preparation of miRNA / A6K mixture

[0326]

[0327] 3.2 nmol (45 μg) of miRNA was administered to each mouse.

[0328] [Table 10]

[0329] Table 10 Sequences of control and miR-3140-3p

[0330]

[0331] The experimental results are shown in Figures 20 to 28 .

[0332] In the group that received one dose of miR-3140-3p, tumor shrinkage was observed at the second imaging (day 10 after transplantation), and the effect persisted until the fourth imaging (day 24 after transplantation) ( Figure 20 ).

[0333] The imaging results were digitized and plotted, and the results showed that miR-3140-3p significantly inhibited tumor growth ( Figure 21 ).

[0334] The survival rates of mice were compared and it was observed that the survival rate of mice in the miR-3140-3p administration group was improved ( Figure 22 ).

[0335] In the groups that received miR-3140-3p twice or three times, similar to the group that received miR-3140-3p once, miR-3140-3p significantly inhibited the growth of malignant pleural mesothelioma ( Figures 23-28 ).

[0336] The survival rate of mice was further improved in the group given miR-3140-3p three times ( Figure 28 ).

[0337] Experiment 8.IC 50 Calculation of values ( Figure 29 )

[0338] The IC50 value of miR-3140-3p was calculated using malignant pleural mesothelioma EHMES-10 cells.

[0339] The steps are shown below.

[0340] 1: Add 0.25 μL of RNAiMAX (Invitrogen) to 25 μL of serum-free medium (SFM).

[0341] 2: miR-control and miR-3140-3p were serially diluted to a final concentration of 40nM, 20nM, 10nM, 5nM, 1nM, 500pM, 100pM, 50pM, 10pM, 5pM, and 1pM, and mixed with SFM / RNAiMAX complex.

[0342] 3: Incubate at room temperature for 20 minutes.

[0343] 4: 6.7×10 4 cells / mL of cells were added to each well.

[0344] 5: Incubate at 37°C and 5% CO2.

[0345] 6: Five days after transfection, the cell viability was examined using the Cell Counting Kit 8 (DOJINDO). The steps are shown below.

[0346] (i) Dilute the Cell Counting Kit 10-fold with culture medium.

[0347] (ii) Add 200 μL of the diluted cell proliferation-toxicity detection kit to each well.

[0348] (iii) Incubate at 37°C, 5% CO2 for 1 hour.

[0349] (iv) Use a plate reader to measure the 450 nm / 600 nm values.

[0350] In addition, as a control, the same control RNA as that used in Experiment 7 was used.

[0351] The results are shown in Figure 29 .according to Figure 29 , indicating that miR-3140-3p also exhibits a proliferation inhibitory effect on the malignant pleural mesothelioma cell line EHMES-10 at very low concentrations. Calculate IC 50 The final concentration was 0.57 nM.

[0352] Experiment 9. Comparison of antitumor effects with chemotherapy agents ( Figures 30-33 )

[0353] To investigate the relative superiority of miR-3140-3p's anti-tumor effect, the tumor suppressive effects of cisplatin, a first-line drug for malignant pleural mesothelioma, and miR-3140-3p were compared in vivo.

[0354] Six-week-old male mice (CB-17 / Icr-scid / scidJcl) were used, and tumor cells used were the malignant pleural mesothelioma cell line EHMES-10 expressing the luciferase gene.

[0355] The steps are shown below.

[0356] 1: Administer 0.1 mL of a mixed anesthetic of medetomidine hydrochloride, midazolam, and butorphanol tartrate per 10 g of body weight into the mouse's peritoneal cavity.

[0357] 2: After anesthesia, shave the mouse's chest and cut the epidermis with scissors.

[0358] 3: Use a 27G insulin syringe to transplant 100 μL of tumor cells (3×10 7 cells / mL).

[0359] 4: Four days after transplantation, tumor cells were imaged using an in vivo three-dimensional multimodal imaging system (IVIS SpectrumCT in vivo Imaging System).

[0360] 5: After imaging, mice with successful transplantation were divided into groups.

[0361] 6: Administer 0.1 mL of a mixed anesthetic of medetomidine hydrochloride, midazolam, and butorphanol tartrate per 10 g of body weight into the mouse's abdominal cavity to anesthetize the mouse.

[0362] 7: After anesthesia, 100 μL of the miRNA / A6K mixture was administered intrathoracically to the miRNA-administered group, and cisplatin (6 mg / kg) was administered intraperitoneally to the cisplatin-administered group.

[0363] 8: Starting from the initial imaging, imaging was performed every week to observe the tumor growth.

[0364] Mixed anesthetics were prepared as shown in Table 8. MiRNA / A6K mixtures were prepared as shown in Tables 9 and 10. Cisplatin was prepared as shown in Table 11 below.

[0365] [Table 11]

[0366] Table 11 Preparation of cisplatin

[0367]

[0368] In addition, as a control, the same control RNA as that used in Experiment 7 was used.

[0369] The experimental results are shown in Figures 30-33 As shown in the figures, miR-3140-3p can exert an anti-tumor effect equivalent to or greater than that of cisplatin, the first-line drug for malignant pleural mesothelioma. Sequence Listing <110> Limeiji Co., Ltd. Hiroshima University, a national university corporation <120> Pharmaceutical composition for cancer treatment containing miRNA <130> TDMP1701F <150> JP2017-216336 <151> 2017-11-09 <160> 32 <170> PatentIn version 3.5 <210> 1 <211> twenty one <212> RNA <213> Homo sapiens <400> 1 accugaauua ccaaaagcuu u 21 <210> 2 <211> twenty two <212> RNA <213> Homo sapiens <400> 2 agcuuuuggg aauucaggua gu 22 <210> 3 <211> 90 <212> RNA <213> Homo sapiens <400> 3 ccucuugagg uaccugaauu accaaaagcu uuauguauuc ugaaguuauu gaaaauaaga 60 gcuuuuggga auucagguag uucaggagug 90 <210> 4 <211> 123068 <212> DNA <213> Homo sapiens <400> 4 gtgagtggcc ccgggagagg gaattgaggg ggagaaagtg ggaggatgcc ggcgcttcct 60 cctggagttt tgctgatgtt ctccagtagt gttgggagtc tatcaatgag ggagtctagc 120 tttattcacg gaggggggaa ggtgttaggg aggcctgtat tttgtaactt tttagctctt 180 tgtacgagta atgcaagtat gcaggtttct gtcggaggag tcttttctcc aaagtgaata 240 ctcgcacctt tctggccagc agttggcaaa gggaaattga ggaagccaga gcatatgtgc 300 gcacagaggc catctgtatc tgtaaccttt tcctggtact gtgggtgtgt gcggtgtact 360 ttttgtttcg ggggtactct catataggtt cccgaatgag aactacttaa cctgtggacc 420 cctgaaagta aaattccttt tttaaaaaac aacaacaaac ctgttttgag agaggttcat 480 ttcagtacct attggtacag gagttaacct tctcagttac tgggtccaat ttcatgtgtg 540 tcaggaggac actgtaacag atgtcagtta ctcaggaact tgagttgtta ggaatcacaa 600 cttacttggg gaagagcatt tatcacatta atcattttat aaaagttgtg attttttccc 660 tttcaccccc cccttttttt ttttagagta acaaattaca gcacttttt atttggtttg 720 aggctttgct tttttgaatt atctttattt ctgtatcaat ttaggataca tctttgatat 780 ttaagtcagg aatgattttt tccttcatt attttaaagc tgaagtttat aaaacctttg 840 acttgtattt taggtatctt gtcagagtac caaattaaag gtttatgaaa gtaattaata 900 tttcatatac agaccttaag ggttaaacat agagcagaat tttatgtaag aagacataga 960 1020 cactgctgag agatactttg tgggaatgaa tgtaagcctg gggttatctc tcttttcgaa 1080 gttctccatt caggatcttg attagattaa tttaaaactt tctcaaactt aacaatgttt 1140 ggtcctttt tttaaagtaa tgagttctgc aagtttatta gcctgtgtat tatgtgacag 1200 ttcatttaca tattccatac ctgtgtccct aaactttcag gacacagtca gagtttgtgt 1260 ttcaagaatt atcaggacaa gcctcagttc atcttttctt aattttatgg actttcatta 1320 tttctaccat cagtttctcc aactgttgtc ttagaataat gtctttcatt tgaccacttt 1380 tccctctct ggaacttctc ccactgaatt gtttttcttt agttgccttg ttatgctttg 1440 gtaaggaact ttaaattctg tcctttaaat gtgtactgac atgaaaatac tgaatagtgg 1500 atgtaatgtt agaatcagag tcacgtattc tgttttcac taagatattg caaagagaaa 1560 tgtagtcatt ttctaaaata ctgtacccaa aatacagtag aagctgtatt ttgggaagga 1620 ggggaggaca aactaagaaa caaactatag tttgaatgta ggttgcactc tgtcaaagtt 1680 gctactaac tttaggacct acttttattg cttatggatt ggttaaaaat tacggtattt 1740 tttttttttt tgagacagag tcttgctctg tcacccaggc tggagtgcaa tggagcgatc 1800 ttggctcact gcaacctccg cctcccaggt tcaagcgatt ctcatgcctc agcctcccaa 1860 atagctggga ctacaggcat gtgctaccac gcctggctaa ttttttttgt atttttagta 1920 gagatggggt ttcaccatgt gggtcaggct ggtctagaac tcctgacctc aaatgatctg 1980 cccacctcgg cctcccaaag tgctgggatt acaggcgttg agacaccgcg tcctgccaaa 2040 aaattatggt aatgttttat tgcacgtttg ggtagaaatg acaaagtttt tggggtccct 2100 gcctttgaga tgcttttact tgtaggtggt ggagacaatc aaacacaat tgcacaagc 2160 tataggagag gggggataga ccaatattta tctaagaccg cactggatgt tagatattgt 2220 caactatag atgtgaatat atttttacat tttcactag ggaatgttg ctttggacg 2280 tgtacatata gaacatattg aagtattgaa gccaaatctg ggaagttttc ttttaggaag 2340 aaaagagcaa gtggagacac atattag acttttggaa ttgaaggca tagggacag 2400 aaaaattac gaagctggtt tgaaggaat acagatagag gttgttgagt agtgttagg 2460 tcagttgtgt tgtgtagac acatgattac agttcaaga agcaactgag aagagtgttc 2520 ctgagagtaa tttcagatga ctggggagaa attacattt aggtaaagc tgtatgcctg 2580 gattaggatt ttgttttct agggaaccaa cattttatt atatcgtggc tatccaggggc 2640 tatacagaag gaggagtga aaagagatg cttagtgtgt tgaaagtggc ttcttacaaa 2700 aaagagttta gaatgggac agtagacttt gctttggtg tgaatttta gggcaacaat 2760 tggatactgg tgcagtttca aacagcaaa atagtttagc aggtatatata ctgaaaatgt 2820 aaagttggaa ttattttcaa agtatttagg tttcccagag tactgatgga aagtgaagag 2880 ctgaaaagtg ggtattttta gttaggggga aaatctgaat gaatgagaca ctacctaaaa 2940 tagatgtttt agaagtggat aagagttgaa gttaaaaagg aatgagcagg ctttaaacat 3000 ggccaccagt ttagtcccag ggtatattat tctgttattt tgaaacaagc taaaattttt 3060 tttttttttt aaatagggta tataggtccc ttgagattaa gttcagaaga gtatacttaa 3120 taataatttc attgttaagg aatttataaa tagaaggaca gatttgtttc ctcaaattca 3180 tgttttaaag ttcactgtgc attattatcc tacgtttggt cttgatatga cgaagtgagg 3240 ccaaaaatag ctgacagaga aggctgcttc ccttgttcac agttggtgtg tgtctttgtg 3300 tcccatacaa tggaggggat atccctgtgt aggcacagta gtgctgaaca tgcttttttt 3360 ttttttttcc ttttaaactt tttattaaaa aaaagcaact tggcatttaa aaaaatgtag 3420 acatttttgc ggcttgcatt tagtattgac tttaacagga ttaaggattg tgaggaagga 3480 aatatatatt cacacttttt tgtgttcctt agttggaatt ctgcaccttc ctagtagctt 3540 3600 caaggagata ggtctaaggt gattctaggg tgaaaatata gggattggat tatatgccat 3660 atggaggcct tctcttgtca tcctccactt tccacaacat tttttgtgca gtcgaagcca 3720 3780 gtgggaagag tggtaacttc atgtactttg ccttggcaac ttttggattg atagggaatt 3840 agagagcctt gagggtatat gtttgtgtgt gtgtgtgtgt tttagcaccc accagatgac 3900 cccaaaggcc atgcataggc tcatttcatt gtactttgga gatggttctt ggagaagtct 3960 tctggtgctt ctgacatctc attgtgtaga gaagagttg gcaaactatt tttgtaaagg 4020 gccagttagt aaatatttta ggttttacag gccacatgat ctgtcacaac tttcaattct 4080 4140 caattggccc ataggccgaa gtttttggac tcctggtata gacaactgcc aaatccacca 4200 acaacaga tgagctttat tacactacaa agccaggact ggctattttt ggtggtcttt 4260 gttttctaga tgagatgttt ttctctgagt tcatttaaaa tgattctgca taaagcacat 4320 actctactgt acaaaatact tttgccttca tggtgatgaa aactatggat tgagggtcgg 4380 ggtgatacca tctttaaagg gatgcagcta aaaagtaggg actacctgca tttcttatct 4440 aaagataacc acagttggca tttagtgata tactggcttt gtatcatggc caaaagtatc 4500 tgtaaagaag cttgtgggca tacttttgaa accttctgaa aataaatgta aagcatttac 4560 ttcgtgtgta aaattagaag tgtctatggt tggtttgaat aatatgagtc aaattataag 4620 agcattaaag tttgatactg ctatctatta aagtcttaat ctcttgcagt ggctaattca 4680 gtgtgtagaa ttacacatcg caatttttgt tttgttaatt tcaagtacta gtgtatatta 4740 acaaatcact taaatcattt aaatgtgtac tttaaaaagc tttgatgtat atacatatat 4800 atacgtatat atatatatgt acacgtatat atatacacgt gtgtgtgtgt gtgtgtgtgt 4860 gtgtgtgtgt attttttttt tttttgtgac ggggtctcat tctgtcaccc aggctggagt 4920 gctgtggtgt gatctcagct cactgcaacc tccacctcct gggctcaagt catcctccta 4980 cctcagcctc tcgagtggct gggatcacag gcatgcgcca ccatgcccga ctaatttttt 5040 tgtatttttg atagagatgg gtaacaactt ttggattgat agggaattag agagcctcga 5100 gggtatatgt gtgtgtgttt tagcacccac caggtaaccc caaaggccat gcatcatgtt 5160 gcccaggctg gtctcttaac tcctgagctc aggtaatcca tctacctcga cctccctcag 5220 tgctgggatt gcaggcgtga gccaccacac ctggccagca ttgctatatt tttaagagtg 5280 aatctttctc acatgtgttg ttcagaaagt gtaattcact ttgtgcaatt ttacattaca 5340 gttaatatta aaatatttgt ttcatatgtc agcagatacc aacattggat gatggtatat 5400 ttagtttcat aaatcctatt tattttagga ttcccttgtt tatggcaggg gtggagatta 5460 ctcttgcaat aatgatcact ttttagttag tttgaaacct gcttttagtt tatatgtagt 5520 atttctacat attgttactt aaattgaact aacaatttac tttttaattt ttcttcttcc 5580 ttttaaaaaa agagtatata atctgacaat gttagtacat cttttagaag gtcactataa 5640 agttgctttc cctatttatt tggaaaggat tatttcctta ttattttaaa aaatctttta 5700 atttttgtct tttcaagtaa ttttatcatt gtcccaagcc taaggatgag tggcaattta 5760 aaagacacaa ggtgtgcatc ttctatctgc aaatactcca aacagaaatt attccagttt 5820 gttgatactt tgagtggacc agggaaaaat gtgtatgttt ttagtgtaac tgaattgtca 5880 ttacaaaaaag atgagtaaag ttgctgttaa ataatgaatt cttgctgtta atttgtcctg 5940 ttcttagact ttcccccatt aagtataatg ggggaaaatg tacacacaca cacacacaca 6000 caaagtatgt atgtgtagat atacctagcg tattgtgcta gatgttcatt tctgcatgac 6060 tgctctggaa tttaggcaat attaaaagac cttaacaaaat atttttaata tcacttaata 6120 tcctgtttta tgtcttaatg tacttttatg tttttgctgc tttctgatga tacctccttg 6180 gtacttctc atgatacctt tcacagtatg tttaaatgga atgtattttc tcaaagtacg 6240 tgacattttc tgaacactat gggatatata tcttctagta attatatttt tacatgcaag 6300 tatctttaaa aatttcttcc tattacaact taagaattgt gaaacatttg agggagcatc 6360 tgcagtttga gcacttgatc tggatattgg aatgaaac ttaacattta actaaatttt 6420 tctgaggtgt tcttttacaa tttttgagtt aacacttgat ttctgtaaag cagaaggctt 6480 ataagaagaa aatatgagag ccagtgttcg tcttgtatta tcctgccatg cacgtagttg 6540 aaaatcagaa acaaacagaa atgcacaaga gaccttattg cttgagtatc ttctgctctt 6600 cccccatcag acctaaggga cagctagtgg atcagtcaga tactgtgcag tttctgttgc 6660 tatgctgtgt cacctttgcc ctttctttct atctggaaga tagctactgg aaatctggct 6720 gtaagaaaga gatagcatgt ttttttcctc tctctctctg tgtgtttctg tctgtctgtg 6780 tacctgtacc tagtgtattg tgttagatgt tcatttctgc atgactgctc tggaatttag 6840 gaaatattaa aagactacaa aatattttta atattattta gccttttctc tgagaggatc 6900 acatcctctg gctttggcgt tttcatctca cagcatctta aacgaacccg tcaatgttta 6960 ttatcagttc caaatgtgaa gtctcaaggc aaattgttgg tttgtttttg gaagaatgta 7020 tgtgtgtgtg tatatatatg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtatata 7080 atttttaaat ttttaacaaa aattcctgat ctagtcaatg cttatgagag tgtgtgtggt 7140 ttgtataaaa ttattttttt tagagacagg gttgcttgtt gtcaccaggc tggagggcag 7200 tggtgtgatc cttgctcact gcagccgtga ccccctgggc tcaagtgatc ttcccacctt 7260 agcctcctga gtagctgagt agctgggact ataggtgtgt actgccacac cctgcaaatt 7320 taaaaaaaaa attctgtaaa gacagggtct cactatattg cccaggctgg ttctcaaact 7380 ccaggactca agcagtcctc ctgaaatggc ctcccaaagt gttgagatta caggctgggg 7440 ccacagtgcc cggtcagagt gtgtgtattt tttaacagcc ttttaggatt gcatgctttt 7500 taggggggtg aatgaggggt aatatacctt tgcatgacat tctctaggtc tgagaaggag 7560 ttgcttcact aaaagtgtaa tttataatta ccaaatggtt gaaaacaggt ctacctggag 7620 tcagcaacag gcagctagtt tacttctcat ttacgtaata aaatacattc ataatatgca 7680 ttcagtaatt cataattcaa taatttcttg gcttcatggc cttggacaag ctatttatta 7740 tccttttaat tttggtggca tcacctgttg atggaggaaa acgtgtcctt tacatggtgg 7800 ttgttaggat taaatgagat aatataaagc atgcaaagct cttaatccag tgcctggcat 7860 atagcatttg acccatcagt gttaatttat taagttaaag ttgttttaaa gtgtgttgta 7920 gataagaat ttaaatcagg ccttatatta agcccaacat ttaaattcaa cacttgagtt 7980 tgaaataa tactaagaga attctgtgtt ttcaagaaaca tctaaaactt cattaacatt 8040 ttattaaaaa ctgaagaaat gacagaactg ttgggctttt ttttaataga aaagaaagac 8100 tgatttgaac ataactggaa tttgaattta gtttcaaaga tctcagtagt gcatggacca 8160 gaaaagaatc cgtttttgaa tagttagtga ttatgatagt gactgtggtt taaattgccc 8220 atttagaaat agcaggatct aattcagtta tcagcctttt tagttgccca tctctttaac 8280 ccctggaaat aaaaagcttt aaaaaatcat taagaagttg aacggaaatt ttatctgtgt 8340 catttacatc tcaaattaag atcgaaataa ttttgtttac atgattctat tttaactact 8400 taattttagt ttttgttttt tcctgaaatt attagtatgt gggttttaaa aattcctttt 8460 tttgtgtgct taatatttgt taataacaag attggttttc agaaatacct tttcttcgag 8520 tagggcataa tcagtgtttt attggccaat aataataa aatgcttctt gattgtttt 8580 gtatttggaa agaaattcta tgttgagaac agttttggta tgctttcctt cattggctgt 8640 ttattgaata gaactgtata tttaaggtat atgaaaaaaa tctaagctag aaaaaaagac 8700 tgagatacat tcttggaaga aatacttgc aaactatgca tctgacaaag gtctattgtc 8760 caacgtctat aagaacttaa atttacaaga gaaaaacgac cccattaaaa agtggacaaa 8820 ggacgtgaat agacacttct cagaagaaga cttacatgtg gccaacaagc aaagaaagct 8880 caatattact cattagagaa acgcaaatca aaaccacaat gagataccat ctcagactat 8940 tcagagtggc tactataaaa agtcaaaaaa taacagatgc tagtgaagtt gtggagaaaa 9000 gggaacactt atatactgtt ggtgggagtg taaattagtt caaccattgt ggaaatcagt 9060 atcgcgattc cttaaagagc taacagcaga actaccattc cacccagcaa tcccattact 9120 aatgggtata tacccagaag aataattc attctaccat aaagacacat gcacacgcgt 9180 gttccttaca gcactaatca caatagcaaa gatgtggaat caatctaaat gcccatcagt 9240 gacagattgg ataaagaaaa tgtggtacat acacaccatg ggatactgtg cagccataaa 9300 aaagaaggag atcatgtctt tgtgggagt atggatgag ctggaggcta ttatccgtag 9360 cacactaatg caggaacaga aaaccaagta ccgcgtgttc tcacttataa gtgggagcta 9420 aatggtaaga acttatgaac aaatgaata icactgggg tctacttgag gggggggtt 9480 ggaggaggga gagagcaga aagataact attgggtact gggtttaata cctggttgtt 9540 gaaatataa gtacagcaca ccctcgtgac atgtgtttac ctatgaaacc tttacatgta 9600 ccccgaaacc taaaaaaa gtttaaaaa tatattctt agcactgatt atcttgctag 9660 ctgtgacttc tccttttaag gaagtttgc tttagattt ggtgtaaatg tagaattag 9720 atgggtttat ctgctagtgg ctctctagtt agatgattaa tgaatattct agtttaaaa 9780 atttcagcat tttaaatact tttcttt ggtaacgat tggattgc ttcttaggt 9840 ctttacatttt catagtttt caaaaagac tttataatga gttcctggat gggaagaaga 9900 gcatgttctc tctagtttat ttgatttctt cctgattatt atgtatgtaa tactggaagg 9960 ttgtgtaaat aaatattttgg gttgtaagtt ttctttgca tgatttggtgg tctctttatt 10020 gactgctgtg tgaatttgat agtataaact agaatgctta tacagtgagt ggggaagcct 10080 ttttctactg agtgttatgc aggtggattt ttcccccctg cggataaata ctaaactttt 10140 attaccag attagacat ttagacagga aaaaaattt cctttttttt aaaataaatg 10200 agcgggagaa gagagtgggg ttgtacagag gtggggagag aggcagtaaa ggaggggagga 10260 aagaagaggc agatatcagg gagagtggct ccggaagttt tgagttcagt cttagtcaga 10320 ggtcacaccc tgttatttct ttgggttgtg gacatgaggt gttaccactt gttatctgtc 10380 accctttgaa atgatgatta gattattggt ttttattcat agcttttcaa catttgggtt 10440 ctttaaacca ttgaaggttt agtttgtatg ggataatcag tgttatttta gggtgggaaa 10500 atttccacca tacctgctag gagaagggga tggccaaaga gttttgact tacagaggag 10560 ttttttgtt ctgttgtttt ttcctcattg actctatttc gctagctttg tctgagaggg 10620 gtgcttataa ttctatatgt gacatagtag ctgagaggca agctttggag ttgatagacc 10680 caggttccag ctctgctgct ttgtgatttc aggcaagtta tttattccat gtgtgtttct 10740 tttaaaactg ggatgataat aatagtacct gtttccctta tagagtaatt aagaggattg 10800 agtgagataa tgcatgtaag cctttagcac agtgtctgcc taagttagca tccagtaaat 10860 gttagctgct gcaataataa gaaattat agtattaagt tattgttatt tctgtgaggg 10920 tgctggtttt ctgaatgctg agacattggt gatctttgct cctgaacgtg ttactatttg 10980 gaatactgcc tttattcagc agcagattca gttcagattt actgaacacc tactatgcca 11040 ggaattgatc taaataagca aaacaaaaat cctgctctct tgaaacttac tttctggtta 11100 ggagagacaa aatacacaaa acaaataga tgatgtgtca ctcaggaaat ttggttgttg 11160 gactttgtct aagctttcat taaccacc tagcagtctt aacctttaca tactttttga 11220 ttgttcctgt tgctgtgctt gagagtgttt ggaggtaggg gcaccctaaa agcgtatcat 11280 agactagctt tattgtctcc agcttcagct tgatcctaat tttaaggcag ccttaaatga 11340 tagttttcat catttccttg acttactact taaattggct atctcaaaac tttcagtccc 11400 caaaacttgt atttcacatc attcagagag atgttgctcc tcccagctg ctcctctttt 11460 gctctctat gccattttct tagaggagg ggatactaga agcatcttt tagattatt 11520 ttctgactag tctactgta tacttctt tctcatattt tgtgttttct accctttatt 11580 tattgttaac tgatacattt aatttgctta ttttctttaa atatgtgtt ttttttggtc 11640 tctccaatta aattgtgaaa gttttaggt cagggaccac ttttctttt tgaccttgag 11700 cttactctct tgaaaaaaag atattaccac ccagggat tgtgagacct ccaagagata 11760 atgtgtgaaa ggggtcctgg agccagatcc ttaataaatg ttagtttctt ctttgaacca 11820 ctctagttgc tgaactgct gtgcatataa tcagtgctt aaaaatgctt gttaatttat 11880 cttgaattga gttgtgaac ttcaattgt cacttggtgg tagtttttttgtgct 11940 agatagatt caaatacta cttttcaagt gtcagatgat aaatgctggg tcattagtgg 12000 tagctca cagtgattag gagcaggaac ttgagccatc attgttgggg ttcagtaca 12060 ggctaccaca cttactggtt gtatgacctt tggcaagttg tttaacctcc ctcggttctct 12120 ttatctgtaa ggaggggaaa atgatatcta cccacctcat ggttacttct ttgttagtat 12180 12240 ccccaggga catttggcac tatttggtga tgtttctgat ggtcatttgg gggagtgggg 12300 agagggaagg gtgctactgg tatctcgtgg gtagggtta ggtataaaca aggtatagga 12360 cagcatccac aacaaaaaaa ttacctggtc cagaatgcca gccctgccaa gcaacacattgg 12420 gaaacccagc ttagttcctt tgtataaggt actttgccag ttagattctg tatacatgct 12480 gattattgat aaagatgagt cagagacatg gataggcttc atttaacatt cattttaaaa 12540 gacagacatg taagaaggtt agtaggtttc atttctttt aaggttacag ggaaagtact 12600 ccaaaattaa tctaaaagtc cttacacttt tttcagaaac tgagaaaagg ttccagatga 12660 atttactaa tttaattttt ttatgacgag ctattcatgt aaaagtgtat tatgaataga 12720 gggcttatga gatatgagtg ccgtagtgtg tattcataaa gtcaaacgta cacttaaaaa 12780 acaagtatca aggtaaatgg aatgatctat tgggggaaac cttggagctc tctctctttc 12840 catatgtttt attactcacc aagtcaaggg ctctttaact taggatcttg ttttctgtg 12900 tacactttc ctgtttactg tttaaaattg gacccttact aaaaatacag aaaattagct 12960 gggcatggtg gcgtgcacct gtaatttcag ctactgggga ggctgaggta gggagaatcg 13020 cttgaaccag ggagacggag gttgcagtga gctgagatcg cgccattgca ctccagcctg 13080 ggtgacaggg cgagactcag tctcaaaaaa aaaaaaaaa aaaaaaaaa attggaccct 13140 taccattcct tgtccattc aggagcctct taattgcctt gcttctgttc tttctctgta 13200 ttcccacttg aattgactct tctttgctgg gatccctttg ggatcccttc tagtccagat 13260 ccaatctacc cttcagagct ccttccaccg tccccttatt tctgggagag aattcagcct 13320 tatacccta aggatggaat ttgaatgtac tgacttttct gctatttaca gggttgtgta 13380 ttatctttgg aagaattggg aagtcatatc atttctgta tgttgtggtt caggtgactt 13440 gttcacttg tatccaaaca ctggttgtgt gtccatgtat atacagcatg tatgtacttt 13500 aatgtcttatt tgtatgtgtg tgtacatgta tattctttca tgtatatttg tctctacacc 13560 ttgctgtttc ctctgcttgg aatattcttt tcttttcatc tgggaaacat ttgtctcttc 13620 agaccctact taaatattga tctcctagga agtgtgtcct gattaatata actagaatta 13680 gttattttt tccactggtt acccacagta tctctgtggc ttttatagca cttaacatcc 13740 ttatttgtat ttttctttc tactgatctc tcagttcttt gagggcaaga gtcttgtctt 13800 agtcaacacc tgctccccca agtacctaac attcctgcca cattgtagac atatagtatg 13860 ttaacaaatg aatgggagag acaaaaaact ggaaagcttt taaataagtt ctatgggggt 13920 tggcaggagg ggagaccaca cattatcttg tcacctttgt ttccaagtgc ttagtgttgt 13980 gcttgcccat aggtgttcag caaatatttg ttgaatgaat tagaagcaaa tcccaggagc 14040 tgataaaatt ttcatgtgaa cttttttctt ctgcatttct agaaagcata tcctagaagt 14100 aaagtagctt agatattttg gaacatctta ttcttaaagt cgaccttcct atttttgact 14160 cagtagtgaa actttgatcc aatggatact tcctgaatag tgcttttggc tgattccttt 14220 ttcacaacat aggtccgttc tggtgttgag tttgttggaa agatgaatat gtagtatcat 14280 ttttacatca tggaggagcc atcattaagt aacagtgtta aataaggact ggtccccttt 14340 gcacatttgg gcccaaatta agtgagtatg tactcttaag tatgggtaat gattgaggct 14400 attgaggtgt aggaaagaaa gaggacaact ggaggtgaag aagtgaccta ctagatctct 14460 tttgcttttg gtaatgattg attttttttt tttttttttt tgagacggag tctcgctctg 14520 tcgcccaggc cggactgcgg actgcagtgg cgcaatctcg gctcactgca agctccgctt 14580 cccgggttca cgccattctc ctgcctcagc ctccccagta gctgggacta caggcgcccg 14640 ccaccgcgcc cggctaattt tttgtatttt tagtagagac ggggtttcac cttgttagcc 14700 aggatggtct cgatctcctg acctcatgat ccacccgcct cggcctccca aagtgctggg 14760 attacaggcg tgagccaccg cgcccggccg gtaatgattg attttttacc cccagttatt 14820 tttaaagaat tggcaaggaa ggagaggggt atgaatctag aagataagaa tgtagatttt 14880 gtaattcatg atcattatta ttaccatgta ttgaatgttt actgtatgtc aggaactgtc 14940 ctaaggattt ttacaaccgt tatttaactt agtcctcaca gcagttcata tgaaatagct 15000 actgatgttt tatggcaaag gaaacaaatt cagagaaatt tccaagaaca catcggaatt 15060 ttgacttgca gaactgggat tcaaatctag atctgtcata ctccatggtc tatgctttta 15120 atcatgcatg ctgtctctta agttttatt gaaaatggaa agttgtactg acataggagg 15180 ggaaaatgat agaaaatcat cctattggaa ggcagattaa cagactcgtg aagaagcaat 15240 tcccagtttt atgtcattat acaaaatat tgtgaaattg aagtccgtca tttgaattga 15300 tttgcattaa ccctcatttt tgtcttgc tcttggaatc atcatcagga caggtgtccc 15360 agatatgtta gcagtagaat aaatttatct aggcaaaatc tgtctaagat tatggagaaa 15420 actgatttta tatgtgaaat gtgttgttga gtgagagtta aatcttttga aggagattat 15480 ttcaggatga gcctcaaata cattatttag gatttgaaaa cctatggttt agcagaaaat 15540 ctgagaatca acatttgtta gtctcttggg tataaattgc ttaagtcagt gggtatctga 15600 ttattctttc tttctttctt tatttattta tttatttatt tttgagacag agtctcactc 15660 tgtagcccag gctggagtgc agtggtgtga tcttggctca ctgcaagctc tgcctcccgg 15720 attcacgcca ttctcctccc tcagcctcct gagtagctgg gactacaggc gcccaccgct 15780 acgccctgct aattttttgt atttttagta gagacggggt ttcaccgtgt tagccaggat 15840 ggtctcgatc tcctgacctc gtgatccacc caccttcacc tctcaaaatg ctgggattac 15900 aggcatgagc caccacgcct ggcttccctt atgtaatttc ttaaactatt tttgtttgct 15960 gatttggtgt ttgtaattta aaaaaaattt attttttctt cttttacata ctttgtagaa 16020 ctattcccta cccagtgagt ttatttatag atatttcata tttaattaat actgtgagaa 16080 catagttttt atatctgtat ttttgttttt tcattaggat atttaaaata atttttgtaa 16140 ttctgttacc ttaaaaagag ctaaacttag atgttggcct ttaaaaatgt tttgtgaaag 16200 attttctctt ggttccattt aaaatactgt atttgtaact atagttaaat acatttgaac 16260 tttgcccttt tcagaaattt taattatatg cctttataaa attttatcaa aagttacatg caatactaa gtatagagtg ctgaagctga gcgtgatggc ttatgcctat aatcccagtt actcgagagg ctgaggcaaa aggattgctt taggccggga gttggagacc agcctgggca 16440 tcatggcaaa accttgtctc tacaaaata grandmother gctgggtgtg gtggtgtgca cctgtagtcc tagttacttg ggaggctgag gtgggaggat ggttttgagc gtagtagttc 16560 aagactgtag tgagccaga tcctgccact attackttagc ctgggtgaga gagcaagacc ctgtttcaaa father grandfather tagctgggt gcagtggctc atggctgtaa tcccagcaca ttggggagtcc aaggcgggtg gatcacttga ggccaggagt tccagaccag cctggctggc atggtgaaac cctgtctcta ctaaaatag aaaaattagc tgggtgtggt ggtgcgtgcc tgtaatccca gctactctgg aggctgaggc aggagaattg cttgaacccg 16860 ggtggtggag gttgcattga gctgagattg caccattgca ctccagcctg ggcgacacag cgagactttg tcttgaagaa aaaaagaaaa aaataagtat tgagtgctga atgatgttct 16980 ataaaagatt aaaaatgcct aagtggaact aaattctggt aatagaatt taggggttgg 17040 ggtagaaaga atcagataag tacttcaaga ttttcagact ttaagtctaa ggctcattag 17100 tatcctctga cataatctac tacaggtttc ctttcttaga agtgaatgtt aatatggcac 17160 cactatacaa atatatcga tatcggtatt tgagtgttta ttatgtgaca ggcactgttc 17220 tgtgtccttc atgtgtatta cctcatccag tcctcacgat agctctatga ggtaagtgtt 17280 gttaatatcc ctattttata gctgaaaatt tggcatagag aagttaaaca tggtcaaggt 17340 cccaccttta gttaatagtg gagctgggat tgtttccagg cagtctggct ctagagcctg 17400 ggaccttaat cttattcta tactgtctgt gtcatctgta aatttatttc ttatatatta 17460 tttatagaac agtgcctggc acacaataag agccatagaa gtactggcta ttttcattgg 17520 catttaatta tatatgaggt tggcagagca tgcattatta ttccatttgt ttatttatac 17580 tattaattag atagtagact ttattcagat ttctgtgttt ccttttttta aatagtcgag 17640 tttaccgaag ttcttagaaa ctggatgatt gcctccaata atgtggccat gctagatctc 17700 aaaattaact ttttaaaaa aaccacccct ccaactttat ttacacttcc ttagaaatgg 17760 ataaagacca agattgggct tctgttttga tatgtcattg gtttagaaag gcagaaacag 17820 cctggcacgg tagctcatgc gtataatcct agcactttgg gaggctgagg cgagtggatc 17880 gcttgagctc aggagttcga gaccagctgg acaacatggc gaaaccatct ctactgaaca 17940 tacaaaaatt agctgggtgt agtggcactt gcctgtagtc ccagctactt gggaggctga 18000 ggcaggagga ttgcttgaac ccaggaggtc gaggctgcag tgagccaaga tggtgctact 18060 gcagtccagc ctgggtgaca aaataagacc ctgtctcaaa aaaaacaaa aaaagcggaa 18120 acaaccatac taagtttaca gtattgtttg tgtgcctact tggtggaaga aataaattct 18180 tagaagttac actttcttta aaaaattaaa attaaaaac tgtgcagtgt tgagattagt 18240 attaccgctt atcttgctga cttgtgaaat tgaattacat cacttataat aatgtgaagt 18300 tttagaaatt gttttgatga taaagagtag cagcctttaa gagaaataat ataaaccatg 18360 tttcctcaaa tctaaatggt catctgtatg gtattagttt tccatcgctc tacagaagca 18420 gtccccagcc tttttggcac cagggaccat ttttgtggaa gacagtttt ccgtggatgc 18480 ggggaaggag aggcagtggg gaatggtttg ggatgaatca tcaggcatta ggttctctta 18540 aggagcacct aacctagatg ccttgcatgc acagttcaca atagtgtttg tgctcctatg 18600 agactctaat gccacagctg atctgacagg aggcggagct caggcgataa tactccacct 18660 gcagctcacc tcctgctgtg cggccgggtt tctaacaggc cacggaccag taccagttgt 18720 ggacccctgc tctacagcaa attaacacaa atttagcagc ttatctttaca gtttctattg 18780 gtcaggaatt tgggtatggt ttagctgggt ctttcctcag gttctcacta ggctgaaatt 18840 aaaggaatcag ccggggctcc tatctcttct gaggctctgg gttctcctcc aggctcaccg 18900 gttgtgggaa gagttcaatt ccttgttctt gtagatctga tgtccctgtt tgcttgctgg 18960 ctgtcagcca gggaccactt tgagctcctt agaggcccac ccccgccacc atgttcttgc 19020 catgtggcca agttattatg ttgtgtatga ctaaggaaga aaaatgctgg attaaaatat 19080 aagacaaatt cttactttat gtatgactaa ggaagaaaaa atgttgaatt aaaacatgat 19140 acaacacatt attgcttgga cagtgccttg caaaaaaaa aaaaaaagag agttgtggtt 19200 attcttccag ccacaatatc tgcttcagaa atgtcaaatt tattttctac tgttgtgttt 19260 gtgttcttt ttgtaaacaa cttttttgtt tcaatgctga atcatagtat tttacaggac 19320 atttaaaatt aagaagtaag cgtgacttct tattgtacta ctaaatgtac agaatttagt 19380 aataattatg gtgatataaa ctgccattac ccaatttgca agtgtacagg gaatgacagc 19440 tatgttgtga ctgccatggg caaatggtga tttgtaaagc attgttgctt ttttcccccc 19500 atttaagtt gattttattg agatataatt tatatacagt aaactacaag acatttctgt 19560 caccctcaaa agattcctca tgccccttca cagttaaatc cttccctgca ccctcgcttc 19620 aggcaatcaa tgatctgctt ttttattact acaaattagt ttgcattttt tagtatttta 19680 aacagtgagg aaaaaagagg agatggagac aggctatttt taatttttat atttctttct 19740 ttgttcttag agaaatccta gtttcttat taggcattag gttattcct tcagtgtggg 19800 ggtaaagtga ttcttcttga agctttctaa gtatgtttcc tagatgttct tgacctctgt 19860 tttgcctaag ataacttttc tccagcatac ccagagttgg ctctcttaaa ccatacgtgc 19920 ttgtgtagct ccctcatcca tatttctact tattgtcttt tcaggaccgt aaacagaggt 19980 atttttgact tgacattctc agctcctaaa taatcttata gtgttactga ggctttcac 20040 ctgtcacata cccccgtcct agtctcttt tgtgttgctg taatacccg aggctgggta 20100 attatgaag agaagaggtt tatttggttc atggttcctg caggttgtat aagaagcatg 20160 atgtcagaac atctgctttc tggtgagggc ttcaggaagc ttccactcat ggcagagagt 20220 gaaggggagc aggtatcaca tggtgaggca ggaaaggaga gaaagaggag agggggtgcc 20280 aagctcttt tatcagttct catgagaact tacagagggg aaactcattc attaccttga 20340 ggatagcaca agctgttat gtggaatctg ctcctatgac ccaggcacct cccactgtgc 20400 cccaccctca acattgggga tcagatttca acctgagatt tggaggtgtc aaatattcaa 20460 attatatcat cccctagaga acataccctcc ccaccctga gatctcaga atttcttgtt 20520 gagaattcat attacagtat gagttgtagg aaacatgaag gaagatttc ccttctagtc 20580 agttcttata tttacactt gttcatgct ccttggtgtg tatagtgtt tcaggtgcag 20640 gaatgctct gggaagaatg tgctctta gaacgtaga gaagggaac cccaagggaa 20700 gactcaaatg aagtccttaa aaagcccact tagctctctc tgagacagca ttgtccaatg 20760 gatgcaagc gagatagtta atttaaattt ttctggtagc tatgttaata aagcaaaaaa 20820 agaaccagcc aacattaattt ttatatat attttta acacaata tcccaatgt 20880 tattttaaca tgtaatcaat atgaaaacca tgagacttt gatatttaaa attcttattt 20940 taatactaaa tctttgaat cagtgtatat ttatactta cacacatct gatttggac 21000 ttagtcacat ttcagtaag tgctcattag ttagtgacta ccttagtga cagtgtagat 21060 gtagattg aactttg gaaagaca tagcatgtgg actccacaag aaattgtctt 21120 taacaactgt ttgactca taggttagggg ctttagtgtt tcagaatggt ttctatggtt 21180 gagatgtaaa gttttttatt ttttaaagg tagtacatt tcattatac 21240 aagtaatgtc attgttgaag agttggaaa gtctgggtaa aagacaaca 21300 cttcctcagt ccagagataa ccaatgtaa actttattga atttcctct tgggaatgtt 21360 gctttttaaa atcaagaga aaatagattt cttttgtc atattcctt cctgttcaca 21420 ttcagacata cattattatt gatactctt gtttaaattt atgtattctt 21480 tttctcgggc tgtatcctcc atagggtct ctgtgagtgg agtactctgg agcacagtaa 21540 cctgaatggt gcttccctgg attagggtta acatagaaa cttcaatggc tttgtac 21600 tcattgctaa accagtgtag ttgcttcta tttaactat ctgcgatctc ttgcatatc 21660 ctgcagcttt tttagttatt gaggtataat ttgcatacca gaaaattcac tctattaaat 21720 actcaatca ggccggcata atttgcatac cagaaaatttc acgctattaa attackcagtt 21780 caggccaggc gcaatggctc atgcctgtaa tcccagtttg ggaggctgag gtgagcggat 21840 cacctgaggt caagggttcg agaccagcct ggccaatatg gtgaaacccc gtctctacta 21900 aaaatacaaa aattagccga gcatggtggt gtgcgcctgt agtcccagct atttgggagg 21960 ccgaggcagg agaatcgctg gaacctggga ggtggaggtt gcggtgagcc gagatggtgc 22020 catttgcact ccagcctggg caacaggagc aaactccgt ctcaaataaa taaataaata 22080 aatattcggt cgttttcatt gtattcacac agttgtgcag taattatcac tattaatcca 22140 gaacatttc attacctcaa aagaaccctg atgctcatta aggagtcact tcccatttcc 22200 tctttgcgca gtctcctggc aaccactaat ctacttccta tctctatgga tttgcctatt 22260 ttagacattt cttataaatg gagtcataca gtacatggcc ttttgtgttt ggcttctttc 22320 acgtaacacg atgttttcag tgttcttctg tgttgtagca tgcatgagaa cttcattctt 22380 tttaggactg aatagtattc agttgtatgg agggtaccac attttattca tcagttgatg 22440 gactttgggg ttgttctctgc ttttgagat cacattcatt cttcagaac attaatttct 22500 taatatcgtc ctccattctt atcaagctt tcagtggttt cctgttgtct aaaacataa 22560 tagaaaaata tttagtttgc attcagtctt aaagtgta acttcaagtt actttctttt 22620 ccactcttat ttccatctt gttgttgttt actgtgtcta aaatatgtgc tatatatgaa 22680 tttaaaattt atgtagaca tatagataac cttgtcatct gatctaattt ttaaaaagtg 22740 aatttgaata ctgccaaact aaggagtag tgtagtatgg agatttgag aagacaagt 22800 atcagtaag aagaacagt atagtaaac aaaattttt tctgccttgg tccattgaaa 22860 gaaatattta gttcatata atgtgaaca aaaccttaat tttgaatgaa catttgatac 22920 ataggaactc attcaatca ttgatttct ggttaacttt gttagtagtt tgttttttc 22980 tgagtcttt gttttaatcc agatagtcag tctttctc ctttttacat gcttgaatg 23040 gtaaaaatga atatttta cttattctta aaataatttc cagaatgtct tacacacaca 23100 tacacttaga aaaataca atatatagt gatattctct cacattttac agagaaagc 23160 gtagtataca tactttgttt tttaatttca cagtagatct taggtctt tattattag 23220 catactgaga actttctcat tttttcata atagtattgt ttattccatt gtgatgaata 23280 tgctattgtt ttgaaacta gtcccatatt ggtggacatt taggttgtt ccaggtccac 23340 tattacagat atactacag tgaatagtt tgtacatgta tcatttcata tgtatgccaa 23400 tattctgca ggataatttc ccaaagtga aattgctgaa tcaaagata tatccacctg 23460 aaatttgatt accatattt tttaagcataa aggagagat aaaggaat aaatagaaaa 23520 aaagaaact atagatttc aaaaactttg tttatag aaaaaatgga ggattagaac 23580 tttaagtaa ttgtccatgg tcatgcactc cacagaggac tggcatggt gggattcggt 23640 ggggggggcg gggggctgtg tcaggatgct aacccaggtg ttcctgatt taaatagct 23700 gctatccttc ctgttatatt catactgcat gttatgagca aaaggggaga gaagtcgcca 23760 actttttgga gaaaaagaat aaatcccag actttattt tgggatcatc tgaggtggga 23820 agatggcttg ggcccaggag tttgagacca gcctgggcaa catgaagaga ccccctgtct 23880 ctacaaaaaa aaaaaaaaaa attaaccgt ggtgtttgag gcttcagtga gctgtgatca 23940 ctgcactcta gcctgggtga cagaatgaga tcctagtata tgtaggtatt taatgtatat 24000 cgaaggcagc atttcagatt ggtgggggag aagatggatt atttggtaat ttatattgca 24060 gcaactttct attcatttgg ggaaaaagcc ctgtcccttg ctcttactct ttacataaaa 24120 aataatttaa aaatgaaagc aaaaggtaat atcgaaggat gtcgtgaggt tagccttatt 24180 caatagactg acctcagtga gtactgaact catgaaagtt tcattttttt cccagtcact 24240 gtctttgca ttttccttaa ttgattttta acatcacctt ggattaatct catagctttc 24300 ccaatatgtt tttagttatg aaaagtctat ttctcctctt gccccgtatt aggcttgacc 24360 tgtggctgga gagatctgtg gtactgtttc atatgtaccg ccctcctctt tctctcctcc 24420 cttttttact tgttctgaaa acaatgagta aggttaaaaa attatttttc acaaacatga 24480 aaaaggttga tatacgtaa gttttgaata tgggggaaag ttactctcat actgttgttg 24540 ggagtataca ttttgtggc ctttttggag agcagtttga cagtatttat caaaataaag 24600 tacacaggca tcttgaatca gcagttgttc ttccaaaatt tagtagtaca gatatactga 24660 cataacttta cttgaaagaa gaatcctttt tataacttag tgtttattga caagagaatt 24720 agcatttaga gtcatttatt attctaactc ttctaccaaa atggtgagat gtgttgtaat 24780 ttactggacg tttaggttgt tcccaattt tttgtaagta tgaaaaatgc tgcagtgaac 24840 atctttgtct gtgtgctacc cagtcatcac tgttgagaat gtttcttaat ggctatatttt 24900 aggtaagtgt tatttccctt tatttcccct cttatacttt aaggagcaca ggagatctca 24960 gttttaatcg cagctcaatt gcctaaatgg atgtgtgact taaaacaagc tctttaacct 25020 tactgagcag gaggttctgc agatatgggc ctctcagact attttatagc agtaataaat 25080 ggactaccta ttgtcacatt cttcatgatc ctgtagggag tatgtgtcag taggacaacc 25140 cattgagtga cagtcctaac tttcttggtt cctctccctc attgtgaggt cattgtttca 25200 aattgtata tacttactga ttcaaaaac aactccaaca cttattgagg ggtagtactg 25260 ttcccagttg agaattactg ttgtaaaaat ttggcagga attatataag attattcatg 25320 attgttatcg acttatcttt attccttcat ttttttaa agcaggaagc ataatagtt 25380 tacgttcgtt aacctcaata tctactctaa aacatgttgt ttttctgtt attaccatga 25440 aagtctgggt taacaggaga cgagactagc ttctcacag atacatacat taatttgaca 25500 ttatagaaaa atgagactgt atcctgactt gccagttttgg tttgattgg tggttttcacc 25560 ttttttta gactcaggaa aacggtggca aaatagtat aaagggtaaa ttctcatatg 25620 cccttcattc aagttcccaaatttacat cttatgcagt gagaaaaa ttcaaat 25680 caggagatta acatcatgt atactgata gtctacagac tttattcaga tttcaccat 25740 tttctcacca atggccttc tctgtccag gatcacaata tgaaattatt cacgtgttgt 25800 attttagtta tcatgttttc ttagttttct ttaacctgaaacattccag tctttctttg 25860 ccttttgtga ctgttatact ttggagt actggtcagt aatttgtgg atattgcac 25920 aatttgtgtt tgtatgtttt cctatgattc aattaatttt aagcattttt gattaagaat 25980 actgcaaaaa tgattttatg aatcttattt agaggcacat gatgctgatt tgtccagtta 26040 tcagtgatac taattttcag ttcctttcgt taaggtggta tcaggtttgt ccactctagt 26100 tgcttttttt cctttgtgat tcataagtag tgttgattca gattctaggt taagaaaagg 26160 aaaaaaaaa gtatcctatg ggaaggtact taaaaataag tactttggga ccaggtaatt 26220 aacatttctc accatactct accaattttt aacttccttg ctgttttttt ttcttttttt 26280 ttttttgcag tggcacgatc atgagtcact gcaagcctca atctcctggg ctcaggtgat 26340 cctcctacct cagcctgtta agtagctggg actgcaggtg cacaccacca tgcctggcta 26400 atttttcata ttgtttgtag aggcgaggtt tcatcatgtt gtccaggcta gtctcgaact 26460 cctggactca agccatcctg tgttggcctc ccaaggtgtt gggattacaa gcgtgagcca 26520 ctgcctggcc ccagacttta acttttattg atgattttgt catggtgatt ttctgtttcc 26580 atcatttctt ctgtatttac attagtggtt tttggtaagg aagaactttc ccttgttatg 26640 tatttattta atgttttatg tatatcagaa tggactcgcg gatttttttt cccctcttat 26700 atcagatgga cttacagatt cttctatgga tttcatctat tatcatcatt atttattttg 26760 gtgctctaat tatcccaggt ttggccccat gaagcctctt caaggaggtt cctggtcctt 26820 ttgacatgtc tccatcattt tgtgagggct taacttttt tttttctttt tgagtcaggg 26880 tcctgctgtg tcactcaggc tggagtgcgc agtggtatga tcatagctca ctgcaacctg 26940 gatttcctgg gctcaagtga tccccctgcc ttagcctccg gagtagctag gactacaggc 27000 caggtatgtg ccaccacacc cagctagttt tcgcctttt tttttttctc catagagac 27060 agagtcttgc tgtgttgccc aagctagtct taaactcctg gcctcaagca gtcctcccac 27120 cttggtctcc caaagtgctg ggattatagg catggaccac cacacctggt cagaaggctt 27180 aactttctag tagcgcaaaa tgttctagtc tcttcttgtg cttttctctg ccccagccat 27240 gaaatcagcc atttcaccaa ggaatattga ttccttttac tggaaatcgg aattcttcca 27300 ttccccctgc ccccagtact tgtatcttac catcttttta aaagtctttg tgtcttagaa ccgtgttaga tgatctggac acattaccct gatgtacaga aattagttta tacacggtaa ttctttttgt agcagactgt ttaatttgta gcagattcat tttgcactga ttaatcctgg aggatttctt cacaagttac attgtgtcaa atatgttatt tcatgggaac acaattgaat tttttcctta attttgttcg gtatttgata aaaaacttt tctaagagct tccttctaat attached attached ttacatttct catttattta tttggtgtag tgatctcaga agttttttta aaagaaaaat cttgactttg tctcaggtac tctcagttca cttccatgtg ggagggtcat ttgccatcca tccagattac ctttttgatt aggcttttca 27780. gtgtctaa atatttcggt cttttctgat catttaattt ctaatacatg catatgctcc tatgtataat aatagacaa cttcaaattt gcagtttcta gatggttgga aaagggaaac attgtggtgt gtaatttatc agccatcaga tcctagatat ttgagatttt aactaagcaa ggtattagat agaccatgtt gttttggctt cacagaattc attcatattg tgcattacac aatcagtgtg catattgcac attgatttta tctgtaagtt gtctttatca gtggttctca aagtgtggtc ccctgctagt atagtatcag cctcacattg gaactggtta gaaatgcaga cttctcagga tccacctaat tgcagtagtt aattttaaca agcccttcgg tgatcctgaa acatgttaca gtttgagaaa cactgctata atacgtttca tttaaattgt ttcaggttgt gggggtaggg father ccaatttatt catcttctgt gcaatattac ctgtttacct aactcttaga gattattaga tattttgaag aatgtgtccc atgagattat aatggaactg acaaattcct attgcttagt gatatcatag ctgtcatgaa gtcttagtgc tgtaccttac tcatgtgttt gtggtggtga tggtgtacac aaatcttctg cactgccagt cgtctgaaag fathers ggccgggcgc ggtggctcac gccfathers ccaacacttt gggaggctga ggcgggcaga tcacaaggtc aggagattga gaccatcctg gctaacacgg tgaaaccccg tctctacta aaatacaaaa aattagctgg gtgtggtggc gggcacctgt agtcccagct 28680 actcaggagg ctgaggcagg agaatgacgg gaacctggga ggcagagctt gcagtgagct 28740 gagatcgtgc caccgcactc ccgcctgggt gagagca gactccgtct CAAAAAAAAAAA 28800 gtatagcaca tacaattatg tacagtacct atacttgat ataaaggac tgtgttactg 28860 gttgatatat ttacaatact gcactttctg ttgttactt agaatgcact gtttgaactt 28920 taaaaaaata aattcactt gggaggccga ggcggacga tgcttgagg ccaggaattc 28980 gagactagcc tggccacat cgcaaaaccc tgtctctact aaaatacaa aattagctg 29040 ggtgtgtgg tgcacgtctg taatcctggc tacttggagg ctgaggcacg agaattgctt 29100 gaacctggga ggcagaggta gcagtgagcc agtatagcgc caccacactc cagtcttggt 29160 ghagagagtga gacttacct aaaaaaaaaaaaattg haaaaaaggcc tcaagaggc 29220 ccttcaggag gtgttccaga agcagcact gttgttgtag gagattacag ttccatgtgt 29280 gtgattgcct ctgaagacct tccagtggga cattatgtgg agatggaaga cagtgatatt 29340 gatgatccta atcctgtgta ggcttgggtt attgtgtata tttgtgtctt aaaacagttt 29400 tgaaagttaaaaaattttt tttaaaacag gaaaaaggct tataaaata ggatataagg 29460 aaagaaaata ttttatta gctttactat gtgttttaag ctaagtgtta ttacaaca 29520 ggcaaaaaat taaaacgttc aaagtaa aacgttatag taagctgagg ttattacgga 29580 agaaagaaaa aattttaaaaaacttagt acagcctaag tgcacactgt ttataagtg 29640 tatggtagta tacaataatg tcctaggcct tcatatgcat ccacccac tgactcatct 29700 agagcacctt ccagtcctgc tagctttatt tatgatacag atgcaccgtt ttacatttta 29760 tataccttat ttttaata ccttttatat atttagatgt gttaatatca ttgtgctaca 29820 gttgcataca gtattcagta cagtacatg ctgtacaggt ttgtaacctg ggagcaatag 29880 tttataccat ggagatttgt gtaaaagcac tgtgtatatat tcacacaag aagaaattgc 29940 ctgacacatt tctctgaatg tatctttgtc atgaggcgat gcgtgactgt ataatttgag 30000 ccacacatgt tattttaaaa attgcaatac ccttattaat gtaaaaagca gttgaattaa 30060 ttttaagata tttagcctga tggagccatg atattaccat ttcaacataa tttataaaaa aaattgttat tttagattct ctttgtacca agttttgaa atctggtaga tattttatat ctcaatttca acactaactt tttaccgga gtaattgatc ttcctttaga tttcataaag tttatggttg gaaaagtaga ttcacatatc taaatcgttt cagacacact tagtatttc gctacctgaa ttagtacca aaaatatt tttctgtaat atttgcatct aaattggtaa aactggttca tgttttttag tagtagtag tagactttga agcaaaactg tatccatttc aaaattgagc tactgaagtt aagcaaattc atgaactctt gtgtcaactc cgtattactg acatatatt caaaggaga ttggatgtta ggcaaatcta tattaaata agtgtttttc aatgattttt ttgtaatttt tgcagccact ttgcaaaaca ctgtcaatta aaatttatat atgttgattt atgttagaac aaagtgtaaa atctttttta ttggtttgtg ttatgaaac tttaaatttc aatgtaaatt tataagaaag ttcttataaa atttctggca taccttcttc cagtttcttt ttattttact ttttcttgtg ttagcctggt cataaataaa ctctaccttt 30780 ctttggtgct tcaagttaag cttgttcata ggcattgaga tgtaagtgag gaaacaaaag 30840 aatactgcca ttttgtctt ttattactta atagtgaaaa gcatctcttt ctaaaatcag 30900 agttgacatt agagtagatc tttgtgaagt tattccacta tacccagtga gcaaagaaca 30960 cagatgtttt aaatgtattg ttttttatt ttttaacatt tccatgaact ggctaggatt 31020 catatttttg gcatgtacat actgaacaat tcaactcttt acatagggct tttcatagtc 31080 tgtttcagaa agctgaacac agatattttc aatgtgtatc atacagtgga ataaaggaat 31140 aggagaaaca tcaatttttg cttttaaaat tcctaacata gctggagctg tctgttgtga 31200 tagaaactaa ttgtttaata cctagctgaa attctttgac agaggtaaag gattaaaaaa 31260 tatctatgcc actcttgatt tttttttt ttttacagct acatagtgac aactttttct 31320 taagtttaga agttctttca aataaatttc acctaaaaga tttaattggg gccgggcacg 31380 gtggctcatg cctgtaattc cagcactttg ggaggccaag gcaagtggat ctcttgaggc 31440 caggagatcg agaccagcct ggccaacatg acaaaacccc atctctacta aaaaatgcaa 31500 aaaattagcc gggcgtggtg gtgtgcatct gtaatgccag ctacttggag gctgaggcag 31560 gagaatcact tgaacctggg aggtggaggt tgcagtgagc cgagattgcg ccactgcact 31620 ccagccaggg caacagagcg agactgtctc aaaaaaaaa atttaataag gtagtgtctc 31680 ttatatcaca tggctcatct aaagctaaag ggaaatagta atttttcaca ttttgaatct 31740 gttgattttt cgtattatta gaaaggtctt ccatatgatg gatggtgtct taattgaata 31800 tcttccacgt gttgtaaagt atctatttta gtattcctca taattttcta acaaaatttc 31860 tataattgaa ataatttctt taccatctct ttatgtaaat gtgatttct ttctttttggc 31920 gcaagaattt aagccagttt atagctgacc agagttacaa gcccagattt gttaaaaagc 31980 ttttaaacac gtttgttgta catttacttc tgacattgtt tggctaattt tgttgcttt 32040 cttctgattg tagagcagaa agttcttata aaattcactg tgtatttgtt gaaaatgtct 32100 cctaatattg tctactttac ttgtaaact ttaaaaccca agaatagct tttatttg 32160 ctctgtcaca gctaattgta attgtcattc attagaaaat tttagcata ccttcttcca 32220 gtttcttttt actttactgt tctgtgta gcattagctt ctgtatctct acttgattgt 32280 gtattgctgt aatgccttct ttttacttt aaaaatgtgt cctcccttg tccattcatt 32340 tttaaagtaa gaaaatttaat tattattcaaattaaaat taaaaaaaatt aaaaagtatt 32400 gcgattgagt taccagttgt gatttacata ggcatcactg caactgtgt tatttgtgaa 32460 aaacgtattt aagtaaacgc agtacggtgt tagattg agtagaaaaa tactcattct 32520 aactgtaaat tagttaattt ttactgacta gatcagtatt tttagtgta atactagaaa 32580 tgactcactg tatcctgaga tgtggagtat atatgcagt acagtggtca cagtgaatg 32640 tagtactgcc aaagataa aactttcttt agtagaagga cattttacac agcttcagct 32700 tttaaattta aattaagtac aactaataa agctaaaaac tcaatccct ggtaacacta 32760 gccacatttc aagtgcttag tagtcacatg tgctaatag ctaatatatt agaaattaaa 32820 ccttttgaga gttggttatg tatgtgatta aagtattttg gttacttggg actagagatt 32880 acagtcattt ttgatcaggc tgatgtcata ggaacagtac caaggggact tctgaatcaa 32940 gcaccctaga aagagctact tagaactact tgcattttct ttgtggcatc tcttataggc 33000 atgaaaaaat ttcaaacatt tttcatggat aaaaggattt aatcagaaaa gcatttggat 33060 atacatattt gaaatcatag cttgcctgta tgttactaga gtagttggag agtggaaaag 33120 tatctatatt ctaaagactg tttcatcatt tgggtgaaaa accaaaaaaa gagagtaatt 33180 ttgtttaata gctctttcac aataaaaaa aagaatgttc atctgtagag acctatcgag 33240 atctcatcag gtttacaaca aactttagat tagcaagctc aatttcagtt gacatggatt 33300 gtggaaagat tttcagtgga gctcagatat ttaatatcct gaatttggat gaatatacaa 33360 tttctaaaat taagtacttc aactcctctg tggttttaaa accagtagtg gccatacttt 33420 gactagttat taaagcacca acctttttt ctttattact ttgcttttat cctttgagca 33480 agttaggcaa tagttctcc atgtttttga tttctacaga agtaaatgaa tgttattgct gatgtttatt tcattctgtc ttgatctcat gatatgagaa tataaggaga tgtctgaaaa cttgttttaa aaatcctatg aagcataagt tcatgaataa agaaggaagt ggaacttgtc ttgagagaat ttgcctattt agatggtttc caaagtgcat tctgctagtc actagagatg 33780. gtccttgaaa gagttctgta attacktttg aagaaacact gtgtaccata attackggcct attgaatt ttaccatgca cattaatata tcaaaggctt tgagatatct tacaagaaag aaacttgcta aagcttgtct tcctgcatgt cttaagcttc ttccacagtg actttaagtc 33900. ggacttgtct atcctgtgag aaatgctgcc ctctagaggc acaaattcaa ttgctcttaa atttgagtac cataatgctg cctgatctta gtgtgaagtt gtgataatta attackca aatgcatggt aacaaaacca aatagaaga atcttatgtt gcttaatttt aagaaatat gaggaacag aattgcaatt tataatacc cactttttaa attgtacatg tgatattttt ggctgctaat aatcttttga atacatttct gtatatgggg aattgcggac acatagtact tcaagtctcc aaactctgag tctctcctgc tagcagaagc catccttccc tgtgttaaca 34260 accttgctta agacagttac catccatggg gaagctagtt tcctcatacc ccttcccacg 34320 atactcatgt ttccatacct gtaactggag tcagactata tcatgctgca cctttgcagt 34380 cacaatggga agaaaaggat tatatgtaat ttttttaaag tttttttttt tttttttttt 34440 ttttgctgac aaagcagcaa aaccttcagg aatatgtaca gaaatgggtg atgatgatga 34500 tgtgagagag aaagaaacat gcttttgcat ttggctgaat gtattggtat ggtgcagtta 34560 tcagagattc tgaattcatt gttctcgttc aagtagccag gagtggttct aattgtttgc 34620 tccttggtc tcagcattga cttatactaa atgaagttga atgcctaaaa actcatagca 34680 tatatagag gaagaagtca aaagattaaa ggaatagaa ctgatggagt ggatttatca 34740 ctgtgaccat tcacttacct cccctattcc ctctccagta ttctctacta agaggtctgg 34800 aagacacttc attcaccaac ctaatgagaa atactttgag ggcagtgcca gcatatatga 34860 34920. aaagtaattc aattgctttt gtctgtaggc tggaggagat actttcattg aaattgtctt ttttacttca gggggtgtgg ccagattcta ggtaaggtcc aggcatcatt ttcataaggt agcttgacag gcatgatgat cagagatgca ctgacttgaa ttctttttgg ctgtgactaa atgatcatgg atccctacgt ctaaataga gaggaagcct atgatcc tactttatct gtatgagcaa aaaattttag gtctcatagg agaaggcctt acttgaacta ccataagagt 35220. 35220. 35220. 35220. 35220. 35220. 35220. 35220 cttttgtgtt ttgggcatgg ctgcgtgagc ctgtggtcct ggctgctcag gaggctgccc 35280 cctttttgca gtttacttca tgggttatat gagaaaacag gaggagggg gatatcaccg agagattctg atattggagc tgtgtgcaat aactgataag tctctggttc ttacctccat atgaggaaca gagagagtct tgtttgtaca aggcttagtt ataatctgtc aggtttgagg atcttgattg gaagcataga cttgatctgt atttgtggtt tctcatttca aatagcctct caatgttgga taaatttgca tgttcatgtt ttatagagtc agaactcaat ttcctagtat tccttgcagc tagggcacaa gcatatgacc taggctttat tgatcagatg catctgtgta 35640 agacatgaat tcagggtcag agaaatgcag ggtaacagct cttgcctgga attgctttct 35700 aatgtgcatg ttgagtgaca agatattgag ctgtttagag gtagcagtga cagagatact 35760 agtgagcctt gttgtcctag gctcagcttt catggtacta gggctgaagg atgggaacaa 35820 tttggtgggg agacttaggt atttttcctg gcatcatatc tccaagtgga ttcttcagtt 35880 ctctgataat tcttggaatc ccctaatata ttaataaatt tattttctct tgaaaccacc 35940 tcaaatagat tctgtttata gcttagagcc ctgattgatc gtctaacttt aaagatttta 36000 tttatcgtca aaatatttta ttttctaat tgagatctaa aaattgtcaa gcacttatac 36060 tctattttt cccttcctag agctctgcaa tcctttgctg tcatttttc ttaccaggaa 36120 tgccaattt tgtacctttt gaattgcttt ttcttctttg ctacttggct tgagctccac 36180 tattgttatg aaacctttct tataccatcc cagcagcctg atggatttt ttcttcctct 36240 gaattccagt agcacttgtt tagcattaa gtgcaaggtg tttttttgtt ttgttttgtt tttctgtatg catcttagct tccgcactaa atgataagct ccctgaaaac tagtactatg cctcttata tcgcttgcat tgtccaacag aatgtcttgc acctattaga ttcaaggttc agcacagtca ccctcataat atatagtgat gagagttgct gagagcaca gtgatgccag gctgaatgag ctgagataat aaactagtta gatgcatagt ctggccatga ggcccaattt ccatcttcct caaggagtct gagacttgcc tctcagtagt tttcgttagt aggtgatcat 36600. atcttctgaa ttactgtctt cttaatgttt tatgagtttt tttttgcctt gacaaaagcc ttctatttct ctcatgcttc ctagttcctt ccattgtgcc ctctgcaatt tcttttcact 36720 aagcttacta tttgcagtct cttaaaattt gtgtaatta tgaaatcaaa throw aaggacagaa agtagtata caaacacctg tgtatctaac ctcagggtca agcagatatt aaccttttgc ctcgtttgat ttccttttaa agttcttccc tccccatact tttctccctt 36900 36960. ctttggaggt actcattatc ctaaagtcct tacgattatt tccctgctgt ttttgtacac ataaaacatt tacacaaaag atgacctgtg tttttttcta gatgtgttca tattgacatg 37020 tgtagattta gttcattcat tgtaactact gtttagtttt ccaggttgaa taatgctaag 37080 ttttatagag ataatgcagt tctacctttt ggcaaataat attgtaatgc tcgtacatag 37140 gtacttactg taattttatc taggatagat acctgaaagt agaattgctg aatcacaggg 37200 ttcaggtgcc actttatcaa gtattgccga gtccagtcca aagtggagct accattttat 37260 acccattaac atgtttccac actttttttt atcaacattt aattttatct agctatgatt 37320 tttttgccta tttgaaagat gagaaatgga gtttgatgat tttcattttc attactttga 37380 tttatagtaa agttgaatgt ctttgcatag tttttgatca ttctagtttc ctattctgtg 37440 aatcttttat gttctttgct gatttttttc ctattgggta ttgaacctta aattgatttg 37500 tggtgattct ttttataatc tggatattaa tggttttggt aatatgcatt gcaagtatct 37560 catagtgtgt gtgtgtgtgt gtgtgtgtgt gtgtgtggtt tttttttttt tttttttttg 37620 agatggagtc tcactctgtc tcccaggctg gagtgcagtg gtgcgatctt ggctcacaca 37680 aattctgcct cccgggttca agtgattctc ctgtctcagc ctcctgagta gctgggatta 37740 taggtgcccg ccaccacacc tggctaattt ttgtattttt agtagagatg ggatttcact 37800 gtgttgtcca ggctggtctc caactcctga cctcgggtga tctgcccgcc ttggcctccc 37860 agagtgttgg gatgacaggc gtgagccatt gtgcccggcc ttcgtgtcgg tttttaacat 37920 tgtttaaaag tttcagattt actacatgag ttcatttgta gaatctctct tctgtatcat 37980 agcttctttg gtctgctttc atgtctttac aatattgtgt taattttaat agttttgata 38040 taaatcttgt tatctgataa ggtgaatctt ctctcaatga aaattttggg tcagctaatc 38100 atatttcacc ctgaccctaa tgaaaattta acagaaaaca aaccctgttg gaaatgtgat 38160 tggaatctca ttgaatttac aggttacagt ggggatagtt gtcaccttta cattggttga 38220 ctgtcattga tatttctgtt caatacagtt ctattttttt cttttttctt tttctttttt 38280 ttttgagatg gagtcttgct tttgttgtga tctcggctca ctgcaacctc cgcctccctg 38340 tttcgagtga ttttgctgcg tcagcctccc cagtagctgg gattacaggc gcctgccacc 38400 atgcctggct gatttttgta tttttagtag agacagggtt tcgccatgtt ggccatcctg 38460 acctaggtg atctacccac ctcagcttct cgaagtgctg ggattatagg cgtgagccac 38520 tgcgcctggc ccagttccat ttttttcttg atagaagtct tcattagatt tttttttttt 38580 aggtttttat gatttttgtt accatcgtga atggcaaatt tttataaaaa tactttttgt 38640 tactggtagc tacaaaccaa ttagtataag agacaaattg ctaagaagca agttgctgtt 38700 tgtatcttga ttttgtatct ctcaatcttg ctgaattctt agttgttttt gtttgtttgt 38760 ttgaggtggt gtgtcttact ctgacaccta ggctggagtg cagtggtgtg gtcactgctc 38820 accacagcct tgactgcctg ggttcaagca attctcccac ctcagcttcc caagtagctg 38880 ggaccacagg tgcatgtcac cacacccaac caattttaaa attatttgta gagatgaggt 38940 cttgctatgt tgcccaggct gctctcgaac tcctgggatt aagcgatcct cttgccttgg 39000 39060. cttcccagag tgctgagatt acaggcatga gccattgcac ctggcctaaa ctcttacttc taatgataga ttctcttgga tacctcatgc aataatcat aataagtagtg aataagatg gtttttgttg ctttctaagc ctatgtcttt atatttttct tctgttattg acctatgtag 39180 gaccacttta ctaaaattgc agcttttcct gggccttggc tttatgtgtg tgttaatgta 39240. tggagtagaa aggggtatct cagaactgaa gtctcccact aagggccaaa agtctcattt ctagtcccta catatgagtc aaggataaa tataggttaa gactagcaac ccattgtagg gaagaacat tgccaacttg tagcctaata fathertttt fathergtta ctgttttttc catgttactg gcacacactt aaagatttct gtttcatggt ggctaagga ttaatttaaa ataatttttt ttttcctttt tgagttgagt ttcactctgt tgcccaggct gaagtggagt 39540. ggggtgatct cagctcactg caacctctgt ctcccggttt caagcgattc ttctgcctca 39600. gcctcctgag tagttgggac tacaggtgtg tgccaccata cccagctaat ttgttttttt 39660 ttaaattttt stable gggtttcacc stable gggtgatctc gaactcctga cctcaggtga tctgcctgtc ttggcctccc aaagtgctag gattacagac gtgagtcacc 39780 acacccagcc taaaagaatt attttgatat atccttttctg catgaaattt ctgtgggaag 39840 gcttttcagg tgatctgatc tgatacagtg ttaggactgg aagtatagct tatactatat 39900 aaatttcctt aattgaatt tcacattatt taggactct gtaccctgaa gctgtctcac 39960 tctggtattt aatgtcctac aattagttta agagagcaag cttgggtaag tttcttaaaa 40020 cttccttata ttgttctt catcaatatt agtagtatag tatcatctcc tatcttatag 40080 attattata gaaatagtt aataatgtaa agcatttaga acagtattag ttattggtct 40140 haacctcctt ttagctgtta tctacagcct ttctgtaga ttttactt tctgggaaga 40200 tagtggtgta ttcctcataa tctccttgta cattccaggt cctacaataa ttctcaaca 40260 ttttagcatc cttacataga ctctccaata tcctgtctt atttccctga tctcctcaaa 40320 tctactgatt ttctctctcc tcagacaagt gatttttcac ttatttgta aaatcctaat 40380 tctggattaa ctcggttatc agattctttc attcctatac cacctgaatg ctgcagtaaa 40440 aagttacctc aaaggacatt taaaaaaaat tataaattca tgattgttga tcacagaccc 40500 taatactgca tgggaatcca ctgcattatc cttgtcagct agtttcctca tctttaccat 40560 gactgtttca atcatctgtt ctcctcagac ctccaacatg ccctttctct ttctacagaa 40620 aacttttcct gttactttcc agtgaaaacc ggagtacttg gtgcaaccct tagttgccca 40680 ctatcttttc tatattttct ttcttcttaa tgttaaaata gaggtagtct tgctttctat 40740 ctaaggcttt ctccctttct ctgcagtacc ttatgctgtt gatgatttcc cttttttttg 40800 tatgtttaac ttttctttac acttgattct tctcgtcagt atttaaacac gcttaattcc 40860 tgctattaaa aaaataaaaa caataagcat taatgggtac cacattactg acctttctgt 40920 tctctttcct agccaaatgc tagaaattat tgtttccatt tctcaccttt gactcacctg 40980 tttagtttat tcattccact gtaatagtat ttgcttatga taccaacaac ctctctgtta 41040 gtaaattaag tgaatatttt taaacttggt cttatttgat ctctcacttg gtgtgctagg 41100 gcttctataa aataccacag actgggtggc ttaaacaaca gaaattaatt ttctcactat 41160 gtggaggctg gatgtcaaag atcaaggtgt tggcaggttt gttttcttct gaggcctctc 41220 tccttggctt gcagagggtg ccttcttgct gtgtcctcac ttggtttttc ctctgtttgc 41280 atgcatttct ggtgtctgtg tccagattgg attagggcct ggaagatgaa tttactcacc 41340 tctctaaagg ccctatatcc aaatacagtc gtgttctgac gtactggggg ttagggcttc 41400 aacacgtgaa ttttggggga gacagtttgg cacataatct cctagcaggt ttaaacagtt 41460 ttgaaaaact atccttggct ggacgcattg gcttacacct gtaatcccaa cactttggga 41520 ggccgaggcg ggtggatcac ctgaggtcag gagttcgaga ccagcctgac caacatggtg 41580 aaaccctgtc tctgctaaag atacaaaaat aagccaggtt tggtggcaca tgtctgtaat 41640 cgcagctact cgggaggctg aggcacgaga atcgcttgaa cctgggaggc agagtttgca 41700 gtgagccaag attgcgccac tgcactccag cctgggcaac aaagcgagag tctgtctctg 41760 gaaaaaaaaaaa aaaaactatc ctttaaactc tttggttttc atttgcctc 41820 tctgatctat tgctcttcag ccttttttta acaggcttct cttctgcttg gttattaaaa 41880 gtagaaattt cttgagtctt ggtccttttgg tattttctgc ttctcttact tctgttattt 41940 ctccccaggc agtcttacca ctttgatttc catttatgaa ggaactgcat acctgttgtt 42000 ccagcactta atttgcctga gtttcagacc tatttaataa tgccatttag cttatcctag 42060 aggtacctta aaaaaacgag ttcaaatctg aactcataat aatccccatc catgtgattt 42120 gaccctaatc tacctcctta gccttactat tctttgttac tctttgccat agctgcacta 42180 tagcaaagca cggcctcttg gtccaggcgt aatacctt ttcctccaga gtctttgctc 42240 ttattccta tgttaatatg ctcctcattt ttcatttaca acattaccca gttttcaata 42300 catacaaaag ataaaaacat tagttattag ggaaatgcag acttaaacca taaaataatc 42360 actaaaacca actagaaggg gtaaaattaa aaagactgtc aactacaaat attctaggaa 42420 gccatccaga acactcgtaa attgctggtg tgagtataaa atgggagagc cactttggaa 42480 taccactggc aatttcttat aaatttaagc atacaccttt ggatccagca attctacttc 42540 taggtgtttt cggaaaagga atgaaaacat gtccacaaaa aacttttaaa aattatattt 42600 acagtcgatt tactccttac agctgacaac tagaagcagc ccaaatgtca ataggattaa 42660 tgactaaaaa ttttttggta tattcataca atggaatgcc actcagtaat aaaagaacta 42720 cagaatggca aatgtacaca acatgacatg gatgaatctg acatacttgg caaaggaagc 42780 tggacatgat actgtattat tccatttata ttaagttcta gaagaggcaa agctactctg 42840 gagtgaaaaa ataaaaacag aacaaaggtt gccttttgct tctggaaaat ggtgatattc 42900 aactgggagg gtgcataagg ggccttcttg aagtgatgaa aatgttccat atctcataga 42960 ggtgtgtgtt acatgggctt atctattaaa gttgtacagc taagaagtat gtatttcaat 43020 ggcatatatg tatcttagat aaaataaca agttttatct aaaaattata gaaataattg 43080 agttaggtga cagggagtgg gaggtgtaga tgaaagaaga attgcagaac gttggtggtt 43140 gctgaagttg agtaatggat gtggggaagt ttagtatact attttgtttg ttttttgtgt 43200. gttcaaagtt ttccatata agatcttttt aaatcaaagt tacgaagaca cttaaacagc acctgtggtc tgactgccag cttaataaag aatgcttact aatgtaatt tcttctctgt gaatcgtacc ctgattcagc actcctttct ccccaccagc cactatcctg aattcctctt 43380 gactttttaa gacatcttcc aaatatcatt ctaaacgtca cgtccatggg ggaaagcctt ttctgattca gaacactcac tagttttaag tgcccctgtt aagtcctttc atagcttttta 43560. 43560. 43560. 43560. 43560. 43560. 43560. 43560. 43560 ttttggaggg aaagatatat ctattcttgc tgttttaatg tctagaataa taatacattt attgaatgat tatgttggtg tagtttttta aaaaaattga aggataccca aattgaagag ctattctatt actgcttatg ttgtaaggtc agtatgttat aaaatgtatg aatgtgagag 43740 aatgactgag aatgataat ggtttctttc tgattttatt ggcatctgat aaaaacaagg ggcaataaaa ctgtgttatt agatctgga ctatatccgg aaagtcctgt cagttggttc tcaaatgccc ttgagcttta tttgcttct tccttattaa tgtattaagc cgtgtgagtg 43920 aaagacccct ttcctcttta caaagaatat tctaaatcac ctcttttttc tctcttctct 43980 aatgtgcttc ttcctttgac tattagtttt ggtatttatc agggacagcg atctttaaga 44040 gcttgttgtt ttgttatttt ttgtactgct tgctgtatgt tttaaatttt gatatatctt 44100 actgccaaat gaaggtgtga gctcataagt aataaagata gaaaaaatct gctttgctta 44160 taattatacc attaaacatg ttgtccttaa tgcagataca cactattggt attgtaggtg 44220 caggattatg ttttgattt tgccagttca tatttccatg gagtatttag gcaattttaa 44280 caacatagat ttctgtaatg aatgtttttt taacttatgc tgctgcttga gagacagagt 44340 cagactgcca gggttgagt cctatgccca atattccta gctctgtgac ttttgagtta 44400 tctgcttttt gcctgtttct tcctcattaa aacagagata ctaagtgtac cttatagtgt 44460 tgttgggagg gctatttgag gtagtatatg taatgcctgg tacttattaa atgttagatc 44520 ttttttactt tcttgggttc tagggagtcc aataagtac aaatttttcc tctaaggttt 44580 ttttctttat tggtggcaaa atatacatag tataaaattt acatttcaac catttttaaa 44640 tatacaattc agtggcatca agtacattca caatattttg caaccatcca tctctgtcca 44700 tttccagaag ttttcatca tcgcaataa aaacttgata cccattaaac aataactccc 44760 atctttcctc ccctgatttc ctggtaacgt atgttatact ctgtctttat gattatgact 44820 attctaggta cctcataaat agaatcatac agtgtttgtc ttatgtcct ctcatttcat 44880 ttggcataat attttcaaag ttaattcatg ttgtagcgac ttctagttcc atttttgtg 44940 gttgaagaa gtacttccct aatagaaatg aaaacatgtt tgcaaggctt tttttaaaga 45000 atgcttatgg atttagtcat aataggtaac aactgaaaac attggtatgg ctgggtcaag 45060 ttggactaat tcactgtagc ccagggtcat gtaagaaacat ggagttttca aggtaggcat 45120 gggggtggta ttgaggggag ggtagtaagc ataaaagaca gtgctcagaa gaagataagg 45180 gtgccaggtt tcagttccag ggatgttcac agtaaggatt acagtgggct aaattttaag 45240 attaattta taaattctaa acacatcctg ttgactttaa ctgcaactct taaaatgtat 45300 caataacatg actttataat tcctggaaac tgatattttc caatacttt gaagaggttt 45360 aaaatatagtt gactaatatt agaaccaata tttcatgtat tgatttttct ctttaagtga 45420 cagttagttt agaaaatgct aaacttaagt tagcagtata gagtaggtat atagtatac 45480 tgagtatgaa tgtcttggta ggcttggaag cctaccatttt atgtcctctt gaggtacctg 45540 aattaccaaa agctttatgt attctgaagt tattgaaaat aagagctttt gggaattcag 45600 gtagttcagg agtgactttt ctaaaaaaca gaactgagca ccatacacta cttcttatag 45660 ccttttaatt actgccaatt gcctagaata aagttcaaat tcgagggcaa cacaaacatg 45720 gccctttgtg aactgacaga catttcctaa taattcctta catacatgat acccttgagc 45780 cttacagaat taagaatttc tgaatttacc ttggtgtttg atgcatctgt gtttctatac 45840 gtgctgttta tttacctaaa atagactatt cctctatttag cctcaaaagt ctcatggaag 45900 gttttaaaaa atcctgtcta agctctgtta attatattct ttatactatt attttagta gttaatatta taaactacct tttacagata cctggcttac tccctaatt gagttgcttg agggcaggaa ttgtgtatta atctttgctg tattttcttt gccttgctta ctgtagttga ttggtgctaa ttgaataaat gaacatttat gcttttcttt ttgagaatat fathergggta gttcctttag ttgtttata gaagatagca cagacttcta tacagattgg tttttatggg aaaacacaag aatatta attack aatttcatct aaatttct gcagttggag cgaatattt ttagttatt aacttaccta gagtggaaga ttgaattttt gaatgatagt gttttagtta ttaaagtaaa tggcatgtaa gagaactttt aagttcatgt ggcaaaacag ggaaaattg caaagttaga gtctgtaagg tttctgatgt ttcatagact aacaaaaggt tgctttatta gcagcattaa tgaacgaatc gctttattgg cctaggcata ctggtagcat tgtcgttcca aagagctgag agttcttatt tcaattcatg attatgttag acaagtgaag tgaaagccgt tgaccttctc ttaaggagaa aatagaaagt ttttacaaat agattataga ttaaagcctt ttaggac tgatgagaa ctaattact gctaaatcac 46680 ttgaaaaattt tatattttttgcaccag tcttataaca gtaggtttt tatagaccta 46740 ttaattgata ttaaaata taactttaat aggattt tgtagagtta gtcaaagtga 46800 ttgacaaag caattatta aaatagtcaa acttcaatt ctccaaagaa tgttcagtttt 46860 taaaagcaat atgagataca ggaagtatta aactggagat gtaatgccac ttggatggca 46920 tacttttaac attatttt atttgtttta atggaatgca ttttgcttat tagaatcatt 46980 ttggaagtgc caatttgctt ctgttaattt acattaaaga ttaaaatagg aaccactggt 47040 gaccttctaa atcaagttc ttcaaacgg ttgttttaa cagcaagaat tacagaacta 47100 agtattgtat agctattaaa actgaaaatt atgtagcagc agtccatttt aaatttaaca 47160 atttttaatg atacttcaa atttaaaaaa tachaggag atattagat gcttatgtat 47220 ctgtactgcc aaatttaac aaatgttaac ttttgctat cactgtttca gaacttttta 47280 aaaataatta aaaatataat tgaagattac taatctcatt cttttgcctc tcttctcaga 47340 ggtaattact tttctaaagg tatcctgtaa gttttcaata ctttttacca catatttgta 47400 taaaaagata aacagtactg atttcctttt aaaatgtgaa taataatata ctgttggcat 47460 aactttttaa cttgcttttt tcactcagtg tttatttaca tcaagattta ttcatgttga 47520 tatttgtatg tacttaaagt ttgtttatt tatcctctga attattagtt tggtccatta 47580 tttatgatgt ttagtttgat tacttggtta aggtggtgtg acctgatttc tctattgtaa 47640 aagtatcctt ttccccttga taattaatca ttaatctgtg gggtaatgcc ttgagactga 47700 gtaaacattg tttctcaaca gcctttcacc cagtgttttt aacatccatt attgatttat 47760 gcctgaatta ttggttacat tgatgcttgc aaaatgattt tctacatcta ttatctttc 47820 cacatttatt agctggcatt cttctttctg taaaggagtt tctgtccttt cactaagggc 47880 tcatggtttc ttcattaatt cggtgaacta aaatccatta ttgttatgta gtcatgcact 47940 gcatatacga cattgatccc atgagattat aatggagctg aaaaatttct atcgcatagt 48000 gacgttgtag ctgttataac atgttaggac taacgtcaca accacatat tacatgtttg 48060 tagtgatgtt agtgtaagtc aaatctactg tgctgccagt ctaaaagtat agcacatata 48120 attgtgtaca gtacatata cttgatata ataataaca gctatgttaa cggtttatgt 48180 attackatg ctatactttt tgttgttatt ttgaatgtac ttctacttat taaaaaaaaa 48240 agttaactgc aaaacagcct caggcagttc cttcaggacg tactccagag acattgttat 48300 taggagat gagagctctg tgcatgttat tgtccctgaa gaccttccag tgagacagta 48360 tgtggaggtg gagacagtg atactgatga tcctgaccct gtgtaggct agtctaatgt 48420 gtttgtttgt gtcttaggtt tttagcaaac agttttaaaa gtaaaacagg aattttaa 48480 aagaaaag gcttgtaaaaaagaaaa aggaaaa atatttttgt gcagctgtac 48540 atatgttag ttttacgcta aatgttatta caaagtcag aaagtttaa aaactaaaaa 48600 gtttatatga gctaagttt attattgag aaagaaatg ttaaaata gatgtagtgt 48660 ggtttgagtg tatattttaca aagcctacag ccgtgtgcag taacgaccta ggccttcaca 48720 ttcactcttc actcaatcat taactcaccc agagcagctt ccagtcctgt aagctccatt 48780 catagtaagt gccctatata ggcatatgat tttaaaaaat cttttatact gtatttttac 48840 tgtacctttt ctatgtctag atattctcag acgcaccatg ttacagttac caggcagtat 48900 tcagtacagt aatatggtat acaggtttgt agcctaggag caatgggcta taccgtgtag 48960 gcttgtgtaa atacactctg tgatgttagc acagtgaggg aatagcctaa caaacacatt 49020 tctcagaaga tatccctgtg gttatgtgac gcatgactgt gtatcctttg gtgactcaaa 49080 ttgttaaaat ttagccagcg agaactcaat cagtctggtt tctgtttctt tgacatgccc 49140 cctcattttt atagcaccag tttgctttgt ggcacaacaa aacattctct ccttacctta 49200 tggttttctt accccagacc tggacttggc tattttacca aaagttcttg tttctcttag 49260 tgggggaatgg tatttggaag ccaacatcat ggatgcatta ctgggtgtca ttgcttctat 49320 tggttctttt cattagacag aataagaaaa tatactttta aaaactagtg atatttgaat 49380 tcctagtgac accaaggttc ttttctttcc ttgtttcata ttcctcttcc ataatgaaga 49440 tccagtttac caataacatc aatatatgtt tattcatttg ctctgtctta tacatgatat 49500 aacattggaa ttactataggc aataccacta ctaataataa tctcaataaa gtttaagatt 49560 tctatgcagt tttttatta tagcgtatag cccagtgaag gtatatagtc agatcgctat 49620 gcttatagtt attttaatta tatttttcac ataggcaatt tgaaactttt tctaatagga 49680 aggttaagcc tatttactta tcttgacata actagtatgt ttaatctaac tgatatgttg 49740 tatttactgt tgttttatgt tatatatgtt tttcttttac tcttttttaa aaagttattt 49800 ttactaatac aaaaatcttc ctttctctag atatttagaa tgttggtctt agctcttata 49860 gtttcccagt ctttttggta tttttgttgt cattactatg tttaattttg ttaactagaa 49920 ttcatgtttt cttttcttca tccatttaat tgggctttat actttttttt tttttttttg 49980 agacagagtc tcgctctgtc acccacacta gagtgcagtg gcgcgatctc agctcactgc 50040 agcttctgtc tcccaggttc aagtgattct cctgcctcag cttcccaagt agctgggatt 50100 acaggtgctt gccaccatgg ctggttaatt tttgtatttt tagtagagac agggttcgc 50160 catgttggcc aggctggtct cgaactcctg acctcaggtg atccacccac cttggcctcc 50220 caaagtgctg ggattacagg catgagctac cgtacccatt ctatatattc ctttgcataa 50280 atgttgtgtt ctgaggaaaa tttgtgtctg agcatttaat aatttaaaaa attaccatgt 50340 gagtggattt atttatatg aataatgtgc cacatgtaag ttgttctgca gttgattttc 50400 cctttttgtg gagcttttac aatattgtta gtatgtttac ttgtcccttt ttccccttgt 50460 atgtgtagcc aagtaattat aaaaaatggt gcactttgcc atatctgagc ttctcttttt 50520 cccctcaagt agatactgtg catttgaact gcaaaaaggg tcatattctt gctttatcta 50580 taatctcttt taaaggcaaa ggctgatggt tactttttct ttaataagaa tcttgatttt 50640 tcatttgta tatttgatat ttcatttt aagaaaaaaa aatcctctat acatagttgt 50700 tagaaattta tgtagaatgg atgttggaac ccaatcataa ggctgtaaaa ccataaaata 50760 agtagtaata aattttaaaa aattgtatg aattgtatga aacacttcat tctaggatca aacaaatgaa gagagagcta tttttcagaa tgaaaaacca aatagtgttg catgtagact ctattcaaag ttctagtctg taaattaat agcaattcta gtcaaaatag ctgttttatc ttttgagaag ttcgggaagt ttgacaatct gattgtcaaa tatatgttgt agagtatgtt aatgaaacta tccagtgtaa aatttaaaaa taaagaccag tattgttata ttgtactgta ttgcttgcta tactgtagtg gtgtagtaat taaaacacca ttctagtgat acaggaatag ggtccaaata aataaaaact acaggaatag ttgtatacac atgcaagtgt gtgtgtgcac acacacacac aacacagaaa gggttttttt ttgttttttg tttttgtttt ttggagacag ggtctcactt tgttgcccag gctggagtgc agtggcatga tcatggctca ttgcagcctt gacctcccag gctcaagcaa tcttcccacc ttagccttgt gagtagctgg 51360 gactatgtgt gccactgttt ccaactaatt tttgtacttt ttgtagagac tgggttttc 51420. atgttcccta ggctgtctt ggactcctgg gctcaagtga tccttcacct cagcctccca 51480 aagagctggg attacaggtg ttagccacca cgcccagcct caaaagcttt tttttttt 51540 tccttataaa gagccatata tctaaaaagg gaacagatt tgactctatt acatggaat 51600 tctgtgagag aaaacatttt aaagatca gacttag tagaaaata tttgtacat 51660 atagcaagt ttcacaac atttaataaga ccttctaaaa atttaataaa ttgaaaaaat 51720 gggttatgaa taagtacaa tattcaag agtgtacaca attagtttt catagaata 51780 tgcataaga tatatgtaca agtagttaa ttttagcatt atttatata ccaaatata 51840 atattccaac aaatagttg gatataatctg atgttcacc agtagggaa tggtacatct 51900 gtattttaga atattagca gctgattaa aagaataga tctttgtgac caggtatggc 51960 aaaatatccc acattattca tgaaactata gatgatctg tgtagtatga tctcatttac 52020 ttagctcagt aggtctattg ttgtgtaa acttaaaatt atttttatta tcttatagga 52080 taggtactt tagtaacc tattatatt attaggact aaaatatatc actgtaagg 52140 aataaagaca aatatagaat aaaaggaact aagaaaaata ttttacatca gattaattgg 52200 aaatattggt atgaatccat gagtaaataa agaaatatct ctccccccac cctgttctgt 52260 ctaccagaaa atataagaag catggacaat ctcagtagca atggttacat gcatcttggt 52320 tgctaaatat ggctccccat tgaaagaatt caagatgtct tagaaaaata gatgatccca 52380 gttcttagga aaacacacag caagccagaa aacaaggaag tggtgaaaaa ctgaggaatt 52440 atgtaaaaaa gaaccaactc aaaggagttc tagtggccac ctccgaaata atgattgcaa 52500 tcacaggcat atcttggaga tgttgtggat tcggttccag accatcacaa taaaacaaat 52560 attacaataa agtgagtcac acacattttt gttttcctag tgcatataag ttatgtttat 52620 acaatattgt agtctgttaa gtgtgtaata acatgtttaa aaaatgtaca tgccttagtt 52680 tagaaatact ttattgctaa aaattgctaa taatgatcaa ctgagttttt agtgagttgt 52740 tctaatcttt ttcctgctgg agggtcttga ctcgatgttg atgactgctc gccagtcagg 52800 gtgagttg ctgaaggttg gggtggctgt gatatttt aaaaataaga cagcaatgaa 52860 gtttgttaca tcattattc tttgatgaaa tattctctg tagatgtga tgttgttaa 52920 tagtgtttta cccacagtag aaattctca aaattggagg gcagttctct caaccctgc 52980 tgctgctttg tcaactaagt atgtaatatt gtaaatcctt tgttattt tcaatgatgt 53040 tcacagcatc ttcaccaaaa gtggattcca tcacaaagaaa tcactctt tgcttttttt 53100 tataagaagc aacacctcag ccattaaaat ttttttga gatttcagca attcaatcat 53160 gttatcaggc tctgctcta gttctcttgc tattctc acatctgcag tgatttcctc 53220 cactgaagtc ttgagctcct cacatccatg agggttggga cactgattctt ccagagttct 53280 gttaatgctg gtgttttgat ctccactcat gatataatgaa tgttttgaa ggcgtccaga 53340 ttgatgaatc cttcccagaa ggctttcaat ttacttgcc cacatctatc agaggaattc 53400 ctatctatga cagctatacc tttatgaat atatttctta ataataga tttgaaagtc 53460 aaaagggctt ctcaatccat ggctgctga atggatgtgg tggtagcagg catgaaaaca 53520 acatgagtct tctggtatat ctccatcaga gctcttgggt gaccaggtgc aatgagcaat 53580 gtcagtgagc aatgagtagt atttgaacg gaatctttta ttctgagcta cagtctcaac 53640 agtggactta aaatattcgg caaaccatgt tgttaaatag atgtgctttc atcaaggctc 53700 tgttctgttt gtactgcaca agccagagta gatttagctt atttcttaag ggccctacaa 53760 ttttggaat gataagtgat cattgttcca cttggaagtc accagtagca ttggctccta 53820 acatgctgag tcagcctatc ctttgaagtt tggaagccag gtattgactt atcgtttcta 53880 gctaggaaag tactacatgg cttcttcttc cagtagagag ttatttcatc tcaattgaaa 53940 atctgttgtt tagtgtagcc accttcatca gtgatcttag ttagatcttc tagataactt 54000 gctgtaactt ctccatcagc acttgctgct tcatcttgta cttttatgga gacagcttct 54060 ttccttaaac ctcatgaaat aacctctgct agcttcaaac ttttcttctg aagcttcttc 54120 acctctctca gccttcatag aattgaagag aggactttgc actgaattag gctttggctt 54180 aagggaatat tgtggctggt ttgatcttct gtgcagaaca ccaaaccttt gtccatatta 54240 gcagtaaggc tctttcttgt tcctattatt catgtgttca ctggagtagc acatttaatt 54300 tccttcaaga acttttcttt tcctttttta acttggttaa ctggcacaag aatcctagct 54360 tttggcctat cttggccttc atcattcctt cctcactaag cttaattatt tccaactttt 54420 gatttaaagt gagtaatgtg tgactcttct tttcactcca acacttagag gccattgtgg 54480 ggttattaat tggacaaatt tcaatgttgt tttgtcttag ggaataggga ggtctgagga 54540 gagggagaga gatagggatt ggctggtggt tggagcagtc agaacacatg caacatttat 54600 cagttaagct tgccatcttc tgtgtttgtg atttgtggtg gcccaaagca gttaaaatag 54660 taacatcaaa gatcacagat caccataaca gatacaataa taatgataaa gtttgaaata 54720 ttgtgagaat tactaaaatg tgatactgag acacaaagtg agcacatgct atttgaaaaa 54780 ttgcaccaaa tagacttgcc caatgcaggg ttgcacaaac cattattttg taaaatccac 54840 aatatgtttg aagtccaata aaatgaaatg cagtacaagg aggtatacct ataattgtaa 54900 aacctttgat tgaaaaaaat aatccatgag tccagagaga taagaagaaa aggaaggccc 54960 tccttagag aattgtagta gcagtgttag aactggaaaa ctgtactgta aactccaaag 55020 aaacaatctg tgccaacagc atcaatggat gccaaaacct ttaggtgtaa gagtgctgtg 55080 aacatgatac gtatgcagtg gtgcccaatt attctgtaaa tcttgtacga ctacaaaggg 55140 aaaatgtgcc tttgcaatag atctatagat tgccacttga actaagtggt cacacttata 55200 atgggacagc ctgataccat gttccttttg ttatgatata atgcggaatg atgtaacctt 55260 gggtgtattc ttgcctaatg tttatctaca atccagtcag gtttctagac ttgatcttgt 55320 ttccaagaaa tacaggaagt tgtggagtaa gtcagaatac attctgggaa gcagtcagac 55380 aaatctagga tgtgggacat tctgtaagaa aactggccat gagtcctgac acatcattgt 55440 cttaagaaaa agatatgtgt gtgtgcgaga gactattcta ggacaggcga gaccaaagag 55500 attaacagg caaatgttat acataaattt tcatttgccc ttggattgct ctctcaaccc 55560 tgaaggctta aaatagata tctttgagac acttgagaaa actcagat actagcttac 55620 cttatttta cttttttg actagatgtc ttaatggttt tattactttg tagacttgt 55680 tttaaaagat atgttcact actcagtata gtctatgata aaatcagtaa ataaaata 55740 tttgtcattt gcatctctta ggaggttcgt ctccattgat gaagctcag cttatgtgta 55800 actgtcttcc aaagtagctt gcttggagg acatcacta tcatcatatt ctgctttatt 55860 tcatagctgt gtaatcacat ctactacatc cttgtttatc gtttaga ttactgcttt 55920 taagcctatt ttagttcttt aatctgagaa taacagttga ctcagttaat ttcattaaag 55980 caagattgcc tgtaattttt ttatacctt agaaaagtac tatgcccac agcaaaaca 56040 aaacctatt haaaatgggg taaggactt gaacagatat ttctccaag agatataaa 56100 atggccaata aacacatag aagagtctca acaccagtag tcattagaga atgcaaatc 56160 aaaaccacat ttagatacaa tttggctatt agcaagaca cagaaatag caggattgg 56220 gaaggatgtg gagaaaatttg gaaccatgcc tgcactactg gtgggaacgt aaatggtac 56280 agctgctatg aaagacagtt taccagttct tcaaaagtt tgatgtagaa tgattgtatc 56340 atccaacaat ttcactgtta ggcttatctc ccaaagaatt gaagaaggg acacaactg 56400 gataacttat acagcagtgt tcatagcagc attackcata ctaataaa gatgaaaag 56460 gccaaatgtc tgtgaacaga tgaatggaca atgtgttta tacatatagt agaatattat 56520 tcagccataa atacaatga aattttggta catggtacaa catagataaa ccttgaaaac 56580 attgtgctaa gtgaataag ctagacagaa atattgtat gattctactt atgatgagata 56640 ccccaagctg gcaatatat aaagctggca agtataatag aagttactaa ggcctagggt 56700 gagggaggaa tgagaagttt gcttaatgag tatagagttt ctatttggaa tgatgaaag 56760 ttctggaat gatagtggt gatatgta siacattctg atgtactca atgctactga 56820 attgtccatt taaaaatggc taaaatagta cattttatgt atattttatg atacaaaaat 56880 atttttaaag taaaagtttg tattttgatg tacttgtga aaatatttt cactataaa 56940 atttgttgt ttcattgctg cctctttgaa aatgtattaa aaattatg cattttgaaa 57000 tattacagct atataaatga aaaagagtat cagtaaagaa ttttagctca atactctcat 57060 atcatgttat ttattgtcct ttctgtttca cattaagata tacagagtca acaatttaaa 57120 tttgcagatt aaaaaacact ttctgctttt ggccctatag aaataaacca aactggaaaa 57180 ggtgtcatgt ttcctagatt gtggacacag aaaaagaaga gctcaaaagg acaagtaact 57240 cagcacagta gatggttatt gacctgatca tatttaagaa tatcctaaaa atgcaaaaat 57300 gttaagaagc aaaactggga aatactggga tgatatatga aaaattcaaa tgacaaatat 57360 gcagtggttg agtatttatg ggtttttttg gggtttacta ttttttcccc caaatttaat 57420 gtctcctctt ttaaatactt ctaccggatt ctctttagat gatgctgcaa ttggattgag 57480 acattttcat tgtttggctt tgtaagattt ccaaatgcgt atagttgtta aaatacgtat 57540 tcaatgaggg tggaaggaaa cacacaaaaa tagaagtatg tcactctggt aagagatgat 57600 aggtccgatg actgctaata cttttccaaa tggccttatt tggatccttc ttagaacttt 57660 tatattttc tatattgac ctaccccttt ggaactagag tcccattgtc aagaactgtg 57720 aagaatcttg acattttacc ctacttgcaa gctagcagtt actcagttgt agttttatgg 57780 atggtggtta aagatatgag actcctgagt tggagttgaa ggacagttta ttagtgcagc 57840 aagcagtagc agtgaccaga gtattagctt cctttttttt ttttgccgc ttttccaagc 57900 cctggttccc atatagtagt gtgaagagga gggctacatg atgcttgtac acactgtgga 57960 ttgcataaca gatgcggaat cctcagcttc ttacagaatc tgaatagtag tgtataatag 58020 gaagtaagaa tgcctttctt tgctttggag caagatactg tctttgtctc ccaacactat 58080 tgctgtaaaa gtatcctcaa aaggatagtg cagaccaaaa gggtagttga gtgtcttgct 58140 cctaagaggt gcagaaacat gagagtctca tagaaaattg tctcccaata atattttctg 58200 ctcatttcta tactattttg tcttaaggca aatttttttc atgagtatac cactctgatt 58260 tatctgacag aagatagtga agtatctgtt caaatagtta gctggcttt aaaatcaggt 58320 tatttgcttt cttattgttg agtttgagag ttctttcttg attctgggta cagtcctttg 58380 tcagatgtgt gatttgcaag tattttctct gagtctgtga cctgtctttt catattcttc 58440 aatctctttt acagaacaga agttctaat tttgattact atcaggtttt tctcttatga 58500 attgtcttag gaactttttg cctagttgaa aatcacagag tttttttctt tgttttgtcc 58560 agatgtttta ttattttgtg tcttacattt agatctgtga tctgtcttgc attacctttt 58620 gtttgcataa gttatgaggt agagttcagg ttcattgttt ttgcgtatgg atattactt 58680 gttctagcac tatttgttga agagactatc ttttccttcg gtgaactgcc tttttacctt 58740 tgtcaaaaat caattgccct tatttgtaag tatattttgc tggatttatt attctgtttt 58800 gttgatttct gtgtgtgtcc tcttgctaat acatcattgc cttaaatagt aacagtttta 58860 tggtagttat tgaaattagt gttctcaaat tttgttcttt tgctgaattg ttttggatat 58920 tatagtacct ttgcatttc tttataaatt aggaatcagc ttgttgatag ctacaaagat 58980 actttgagat tttgattggt gttatgtta atgtacatgt cagtctgagg agactgacat 59040 tttgccaata ttgagccttc caatccatga atatagttat ttttccatttt tttaggtctt 59100 tgattatttt catcagtgct ttatagtttt cagcatgcag atcctgcaca tattttgtgg 59160 aagtgtatct tttccagatg ctattgtgag tgctactgct ttaaaaattt ttgatgtact 59220 aacttattgc tgatatataa aaatatggtc gatttttaca tattgatttt atattccaca 59280 acttgttaaa atcataatca taaaaccctt tggattttct atatagacaa catgcttttg 59340 aataaaggct gttttacaaa atttcatttt aaatttgtat accttttatt tcatttcctt 59400 tcttaattgc acttgctaga gctttccagg acaatgctga atagaggtgg taaaaacaca 59460 tctttgcttt gttcctggtg ttttattact cttttattat tagtgttatg tttagagatg 59520 gggtcttgct cagttgcgaa ggctggagtg caccggtatg atcaaagctc actgcagctt 59580 caaactgttg ggcccaagtg gtcttcctgc cccgccttc tgagtagctg ggattacagg 59640 catgtgccat catgcctggc taagtttttt atttttgtg gagatgaggt cttgctgtgt 59700 59760. tcacaggctg gtcttgaact ccagtctcaa gtgatcctcc cacttgtact gggattacag gcattagcca ccacacttgg cctcttatta tcattattat father father tatacatata tttatttatt gagacagagt cttgctctgt gagacaggat ggagtgcagt gccacaatct ctgctcactc aacctctgct tcctgggttc aagtgattct cccacttcag 59940 cctcctgagt agctgggatt actggcgttt gctaccatgc cggcgtggt ggctcacgcc 60000 tgtaatacca gcactttggg aggccaagac gggcggatca tgaggtcggg agatcgagac catcctggct aacatggtga aaccccgtct ctactgaaaa tacaaaaatt agctgggagt ggtggcgtgc gcctgtagtc ccagctactt gagaggctga ggcaggaga tcacttgaac 60180. ctgggaggtg gaggttgcag tgagccaaga ttatactatt gcactccagc ctggcaacag tgagactcca tcttaaaaaa atgttatggg atgaaatttt aaaagacct ttgaaagata caagataata ggattcaatt ctgtataagg tagagataaa ctgttgattt gtactagttt gatttgtgaa attack tagctaaat caaataggtg atgggtaatt tgagaattga tttctaatgc tttgtcctag atcattcaaa atctgatgtt cacataacta cttagaactc 60480 ttgactagtt gtctgtgctt tttaaaaacc tttacctggc tggctacaac ttttctaccg 60540 ccataattaa aattgaaaac aaaataatta gtctcttagg aaaataattt acgaacacta 60600 tctaaacatg ctagatttaa aactaccagt atttacatgg ttagaattca tgagcagtct 60660 tcattagact tactgctgaa tgaccagcat acagtcgctg aattcattgt gcatctttta 60720 agggaagatt gttttgcttg tatctttgca gtcttctctg agatctttaa tgttactaga 60780 agttataaag tttggttaat tttcctaata agcctttatc tgattctgtg ggctatttag 60840 gtttgggatg ggatctgttg tcttaatttg gtcaccattg gctcttggct tcaaagtgga 60900 ccctaaacta tattcctagt ctgtctagta tttgtctttt ttttgctgag atatgtgacc 60960 cctggggagg tttcccttat tttcaataag ttaatctttc tcttttagga agaaaagaca 61020 aatttctcat aagggaggga ttttttcctt ttttgttcta gagtgccttt caaattaaca 61080 attttgttca tatcaaaagt tgcccataat gatcactgta agtctcaagt tattcttggt 61140 gaaaatatgc catttagaaa gataagtatc tgaattggaa gaagcatgtt tcatgcttgg 61200 agaggttgtg gagttagact gacttaaaaa gtcagttttg tgcagcctgg gcaacataac 61260 aagacccagt ttctatggaa aataaaaaaa aaattaggca ggcgtggtgg tgcacacctg 61320 tagtcctagc tactccagaa gctgaggtgg attgcttgag cccaggagtt tgaggctgtg 61380 gtgagctatg gtaatgccac tgcacttcag cctgggcaaa agagtaagac ctcatctttt 61440 aaaatatata tacaggtttt tcttcaaaag attccaaagg tactgcttta aaaaatgtaa 61500 gattttctaa gcaacagggc cgagtacttt gctttaaagt ttttatgaat gcctggcttg 61560 gctatctggt tgcttttgaa atcaacatct tactaaacta ttaatgcttt taaaatgtgt 61620 gcagaattac atatttgtaa atttaacttg agtctgtcta ggaaagcatt agcaagactt 61680 ttgtttttgt ttttgttttt ggagacagtc ttgctctgtc gcccagcctg gagtgcagtg 61740 caggtcactg ctcactgtag ccttcacctc ctgggctcat gctatcttcc cacctcagcc 61800 tcctgagtag ctgggactac aggtgtacat caccacaccc agctaagtaa aaagatgtat 61860 ttttcataga gacggggtct ccctatgttg ccaggctgggg cattagcaag attttacggg 61920 aaattttttt tatcattagt agaaaataat aaaggaatccc ttgctggtaa aatttatatt 61980 gaaactactc ttaaacatat ttatataaaa tgaccagaga tatttaattt acctttatat 62040 aataataga aataattga aatacattat taggagattc agatttttta attagtaat 62100 tagtgtgatg gcttaaagtt attgagaggt aatttttcat ctttgattag aaaaacttaa 62160 aaattgtata atttacatac aaagtata tatgagcttt ttatattgat gaactttaca 62220 aaatgaacac acttttgtaa ccacaaccca gatcaagata tcagctttc aggagcttcc 62280 ctgtatctgt catattcctt tacatgaaag gtaattaata ttctgacttt gtaattagag 62340 attagcttgg cttttttttg aatttttata aatcataaag tatataagac tatatgattt 62400 ataagttttt tcaaactggc ttctttccca cagcagtatg tttttgagat ggatatttgg 62460 cttacagcat ttttcatttt cactgaggct tagggtttca ttgtgtgaat atccttagtt 62520 tatttctccc ttctgctgat ggacattcaa attatatcaa ttttgggttc ttacaaatag 62580 tgctgctgtg ataattctcg tacatatttt tttgtgcata tatgtacaca tttccattga 62640 gtgtatgctc aggggtagta tcacttagtc tttgggttta tcttcagctt agtagacact 62700 tccgaacagt ttcccatact gtttgtatta tattattata catttttacc tgcagtattt 62760 tagaatgtca gttgctacag atttttgctt acacttggta ttgtcttttt ttagataaaa 62820 gttagtcatt ttggagggta gtagtatgtc tttgtgaagt tttgtttggt ctttagccta 62880 tcttaaaaat cggtttgttt tttttgttga gttgaagtat ttttaaagaa tatattttgg 62940 gtatgagtct ttagtggaac atgtgcattg ctgatatttt ctcctacact gtagcttgca 63000 ttttcatttt taatttattt aaattttatt ttatttttta agagacaggg tctcactctg 63060 tcacccaggc tggagtgcag tggccttatc atagcttatt gcggccttga actcttgggc 63120 tcaagcagtc ctcctgcttc agccttctga gtagctggga ctgcaggtat gtgccaccac 63180 acctgggtaa tttttaaatt tttttgtaga gacagaatct cactatgttg cccacactaa 63240 tctcggactc ctggcctcaa gcagtcctcc tgcctgggtc tcccaaaatg ctgggattac 63300 aggtgtgagc cactgcgcca gtcatttcct tctttccttc tttctctctt tccctctttc 63360 cctctctctt tctctcttcc tttctctctc cttccttcct tccatccttc cctccctccc 63420 tccctcccca ttcccttccc cttccctccc cctttccctc cctgcttccc tccttccttc 63480 cctccttcct tctctctttc cttccctcct tccttccctt tttccttcct tccttccctc 63540 cttccctcct tccttctctc cttccttccc tccttccttc cctccctgta attgtaatga 63600 aattgtttgt ttgtaatgaa attcagtttt tttatgtgct gtgtattaaa tctatgccta 63660 aatatcgtga cagtatttat cttgtcacta tataagcttt attatttaaa attttatata 63720 tataggtctc taatatatct tatttttttt cccacctttt ctgtggcttg tggatagatg 63780 ttattcattt tactgatttt gattttaaca gtagtagtca tagaaaatct attgatgtgg 63840 cttactcatg agaaagcatt tttattttta tatgtgatat tatattct agtatggcaa cattttctgc tagttatgat atgtgatttt tactctgcag attctttaag aggaatttaa aaacagcttt attcctgact ttagagaagg cagtcagttt tacttaat gtcattttat gtcttattg ttatgttttg tttttgagga gtcatactgg tagtttaaaa atactgagtt ttatcatcaa atgcagctac aatgtttaag cagatgactt aatctccgtg aggcatgagg tgattaaaaa atgtatgtat atgctttttc aatacagag taattgcct ggcagacaag aagagcttca taaatattat ttagtgcttt ttattctaga tttttgaat aaattggact cgacttgatg caaaggattt gtacttaag tttattataa aattattaac cgctagcttt tgtaatagt aaaattgatt tgcccattat acattctttt ttgttatgca taaaatattt taatttttaa gtaccaacat aggatggatt tttaaatgct tcctcatgtt aatttttaa 64500. tttcccactt tattggctct gttttaactc agtagctct agtagtg tgtctaggtg ccacttaaaa gatggtaact agataccaga 64560 atgtgttaca ttatatgttg attgtcagga agaactgaat gcatgaatgc ttccctaaga 64620 cattgttagc atgccgtggt cttgatctat aattttttgt ctaagttgtg atagagctca 64680 ttctttacat ggtctagtaa attcagccaa tgtctttata attcattagc atctctatat 64740 attacctata aaatttaaat tataaggcta tgaaaaaatt gtttcatatg tataatatac 64800 caaagtttta gcatatggtt tggattttaa actgttttac tgaaacaaat taccgtcatt 64860 aaatggaatt cttaggtaga cattacagag taggtgtaac tctgaagttg aaaatggttt 64920 catcttcttt tttaaaaaat tttattatat aggaatctc aaccaccagc aggattttaa 64980 aaaggctatc taaatattg gtaagtaaat attctccatg ttaaatattt tgcgtgttac 65040 ttaagtttac acatatgcta catgaatgac attacaata gtgagtgtaa attatagtta 65100 taattaatat tttaaatttt acttggttac tagaattttt gtctccttaa acctattcca 65160 atccttttct ctcttgttct ttatgttgtg tccagagatt cttcagtgt acagccttat 65220 tattagagt tcaggaag aaatggtttt agtgagcagg atgctaata ctttatgaat 65280 aaaacaggat ttcccctact tgagatttg tagtatttct tttgtga aacactaata 65340 cagatttgtt ctttagccat ccattgcttg actcctcctt gtattaggt cctgtttgct 65400 gcacatgcc aacatgaacc aaatactgtg gtcagggtct atgcattttcc tgtttagatt 65460 attctttgtt ccaagcttaa atatgaaaa attttgtagg tgtctgtagt taagaatttc 65520 aaacttat gatttcatag aaagcttt tacttttta ttttgagta aaggtaggtg 65580 agtcaatctc agaatgtatt ttactcaac tacatagtat ttatactg tgtactatgg 65640 tgattatata gatataaat gatttggtta atcaataag atttttaagt tattaata 65700 gcttcagaat gggaaagag tgctgagaca ttgcataatg agtgtcata gtataggctt 65760 ttggttgttt ttatatagt caatagcaga ttattaagga ggaaatattt agtgataagc 65820 attggcttct tttattatac ttttaatgt gtttgaaca gcaaatattt gaccaaatta 65880 tttttttaa attttatagt aactacagta gtgcctaaa tgttcacag ttatactgtt 65940 ctgtttactg taaatttgta ataaatataa atacttttag gagcaaatga tgccacagag 66000 atctcttaaa cagattttta ctactttaga aggtggtaac tgatttctgg agttgtatta 66060 agtacaaaag agtaacttat tgtcattttt ttccctattg atgcgtatat ttgagttaga 66120 gggaagcagt cgtctttgtg ttatatgctt atcatgtata tttcatctta gcaaatttat 66180 taattttagt gacagtttta ttgagatgaa atttatatac caggagattt catctctaag 66240 tgtacaattc agtgatattt taatatattc accaagttat gcaactacca gtactttgta 66300 atcttaggtt actttcatca tccttcttct ggacgccctc tatcacccag ccctaggcaa 66360 ccactaatac actttctgtt tgtataggtt tgcctattct gggcatttta taaaaacaga 66420 atcataaaat atttgtcctt ttgtgtctgg cttctttaat ttagcatgat atttaaagct 66480 tcactcatgt tgtagcatgt atcagtgttt cattcatttt tgtggctgaa tatttctttg 66540 tatatcattt gtgtattcat cagttaatga gttgtatcca cttctttttt tggctattag 66600 gagcgcttt ctgtgaacat tcttatataa gttttgtgta gatacgtttt tgagtatata 66660 tggatggggt gggattgctc gataatatag tacctgtgtg taactctttg aggaactctc 66720 aaaatggctg taccatttta caataccacc aacaatgtat gaggattgta atttctccac 66780 gacctcataa acacttattg tcagtctttt gtatttcagc cattctagta ggtatgaagt 66840 tgtatcccat tgtgatttg atttggataa tgactaatga taagcatcat ttcacatgct 66900 tattgaccat atacttctt tggagaaata tctgttcaac tcctttgccc attaaaaaaa 66960 aaaagattat ctttttaatg ttgaatattg taaacattct ttatatattc tggaaactag 67020 tcccttatca catacatgat ttgcaaatat tttctcctat ggattatctc tttactttta 67080 tgatggtgtc ctttgaagca gaaaagtttt aattttgaag ttcagctgat ctgtttttg 67140 ttgcttgttc ttttggtgtt atattgcaga tttgttttta aataaatact cactgatagc 67200 ctgggtctat gacaaagttt taatcgtcat aggactacga aaaagcattg gcatttcttg 67260 tgtttgacag tcaaagccca aaggaggcaa ttatccttgt atttgtgctt cagttcctca 67320 gctaattgtt ttaagcaaaa ccttacgttt tgatcccatg tgttactgtg aaaattag 67380 ctgtgtgtga tatgtttatt gatattagtc ttgtgaattt atgtttagtt ttttttggat 67440 tgaagaaggg aggggccatc cttaatagat gttattagtc cgttctcacg ctgctgataa 67500 agacatatac ccaagactgg gtagtttata aaggaaagag gcttaattga ctcacagttc 67560 ctcagggctg gagaggcctc aggaatctta cagttgtggc agaagaggaa ccaaacacat 67620 ggtgacagca aggagaagtg cagagtgaat cgggggaaaa gcccttata aaaccatcag 67680 atcttgtggg aactcagtca ctattatgag aacagcatgg aggtcatcat ccccatgatt 67740 cgattacctt gcactgggtc ccaccacaac acttggggat tgtgagaact gcaattcaag 67800 atgagatttg ggtttggaca cagccaaacc atatcaatag tttattatga caattactgc 67860 atattttatt tcatagttta agaaaccatt gctttttaga ctaaggatta tcaggttctt 67920 atctttcttg tgaagaagga atagattttg ataatctcac tgattttaat cttgtacaga 67980 ttattattat tattattttg agacggaatc tcgctctttc gctcaggcca gagtgcagtg 68040 gcgcgatctc agctcactgc cagctctgcc tctgggttc acgccattct cctgcctcag 68100 cctcccgagt agctgggact acaggtgccc gccaccgcgc ctggctaatt ttttgtattt 68160 ttagtagaga tggcatgtca ccatgttagc caggatggtc tcgatctcct gacctcgtga 68220 tccgcccacc tcggcctccc aaagtgctgg gattacaggt gtgagccacc acgcccaacc 68280 cagattattt ttaagcaatg atattttggt gttttgtaa acttatgtat ggaatatgta 68340 agtttttcct ctattaagta aatgtcttta attttttttt ttttttgaaa tggagtctcg 68400 ctctgttgcc caggctggag ggcagtggca caatcttggc tcactgcaac ctctgcctcc 68460 cgggttcaag tgattctcat gcctgagcct cccgagtagc tgcgattaca ggcatgtgcc 68520 accaaacctg actaattttt gtatttttag aagagacggg gtttcaccat gttggtcagg 68580 ctggtctcaa actcctgacc tcaggtgacc acctgcctct gcctcccaaa gtgctgggat 68640 tacaggcttg agccactgcg cccagccagt gtctttaatt tttaaggtac caatttagtt 68700 ccttattttt tatcgttatg tgacgttatg tgatcagttg aaggtgtatt tcatgtattt 68760 tgacctataa tgttgtctag tttagtttct ggagaaatgg tgtgtaacag tggaatgtca 68820 cttgtcttca aagcattagc tttctgtgta aggttgaggt tgtaatataa atgcgctaga 68880 tgtgttttta ttaggggaat tgactattct tacctttcat gttatttgac agtattcttt 68940 gtcaacttca aataacggcc tattttgatg agattttata gtgctaggat cactgatatt 69000 cttgttagtt gatttaaaat catggtgttc attggctaac agtcacttga gtggctatta 69060 gatgggtaat attgttctct tttttttttt tttttttgag aaagagtctc actctgtcgc 69120 ccaggctgga gtgcagtggc atgatcttgg ctcactgcaa cctctgcctc ctgggttcaa 69180 gcgattctcc tgtgtcagcc tcctgagtag ctgggattat aggcgcatgc catcatgccc 69240 ggctaatttt tgtattttta gtagagatgg ggtctcacca tgttggacag gctggtctct 69300 aactcctgac ctcaggtatc cacccacttt ggcctcccaa agtgctggga ttgcaggcat 69360 gagccaccgc gcctggccag atgggtaata ttgttctata cattgatatt cttatggttt 69420 atgttatagt attcatgga atttagcaat ggaaaagga atgaaaact tattaatgat 69480 gttgttaaat ttcaattgt gatgacagta aggaaagac atattgaga gctacctcca 69540 attgtttata tcaatgtgg taattagag gattttggtg acctatttat ggctgaatta 69600 aggcaaata gctttatat ccgattctt ccttccct tctctgttc tgtgtgctta 69660 ctatcataat attgagtat acattaattt tctttagta tttatattt aataaggtt 69720 ttgatgtcag tagagacttt ttttttcct tgaagtaag taccctttaa accactatt 69780 tgtcactaga gtctatagtc gcttccatat atataggta gcacagcttc tcaggtcatg 69840 tcctgctttg ctgctctgct gaccaataat acaccttgga gatactggtt ctggttatat 69900 gattagaca atttaattgt tctcattag atggatcttt gattactaat cttactcaga 69960 aaggctcaac tggacttgga ttattctaat tgccatact gttttgcac aaatgtctcc 70020 aaatcattga acagtaatac tgacccctttt ttctccaat aaagttattg cagtaatcac 70080 atcattgcag agaatatttc ttaaaagctt tttcaatat ttacttcttt aatgaaaaac 70140 ttaatccaga ttaagccaca tacatagacg tcttgacttt attattttga atacctgaga 70200 tttccaaaat ctctttaact gtcttcacac aatttctagt ctgtcatttt aattaattac 70260 aactgttcat ttcttctgct tttgtttcct cttcatgtgc tgcctagcgt tgctagagt 70320 tcatcagttt cctgccttga gaggtttcta gtacaaatta acattttccc ttcctagtttt 70380 atgcaggttc cttcctggta attttatct ttttgatctg ttcattctg catgttagtt 70440 atttggaacc attctactgt gctcaaatga acagtcctat ccctagttct cttattcctt 70500 tttcatttca tattttatac cctttttcct cagtctgtct taaagaataa agtgttttca 70560 tttcaaaagc ttattatctc tgtttttaat cttagccctt cttcctcta ctatttttct 70620 tccttaat gctccatgct gggttctctg ccttatcaga cttaatcttg aaaagtacgt 70680 tacttccttc ccattatctc caaggttgtt atagtccatt ctaggtgtct ccaatttctc 70740 aactcttact caattacttt ctgaagtttg actattattt ctactagtgt tcagctttct 70800 taagtgtaag taaacacatt tcttacttaa ctaggtagat aaacattagc tggacggatc 70860 tggccgtaaa catgctatta tttccaagat aaaactgagt tccaaatggc taaatctttg 70920 tcttttcact tttcatccat tcctgtcttt tttagcattt gtttttttgc tgcttaacat 70980 tcacttctcc tttgtcttct gtaataaacc ttaatggttt ttctcctctc tctggctaaa 71040 tgtttgtttt ctttgttact gctttcttct tttatatacc acttatatat aaattgggtt 71100 gaagctttgc tcttagctct ttttcattac acatcatttt gaggagatgg tctcgtgttc 71160 attatgtaga ttatcacaaa tttgatgact cagaaatacc acatttttct tagtgacctg 71220 ttttaccact ttctcagtcg ccaggtcctt agcaccccaa aattgttatt tcccagtgga 71280 aagtttgtct tgtacaatgc ttgctatatg gttggaacta agtaaatgct ttttgaatca 71340 tgaactaact ccttatctgt cttttttttt cttaagataa tggttttaac tgtccaccta 71400 ttctcatgtc acaagccctg taatatctct gaccacttct tgtctacact tgttaatatt 71460 agttgtcata ttttggtcct aagtttgact aatgaggaag atgacatttt tgtctgcaga 71520 tggtggaaat aaaaatcaca gagattgtga tttccttatg gttttgtggg taatggtgga 71580 gttaaactt acaacgaagt ttctggtgac atgtttccta gttttcacag aaaacattct 71640 tttttttttt gagacagaaa gtctcactgt gtcgcccagg ctggagtgca gtggtgtgat 71700 gtgcggctc actgcaacct ctgcctcctg gattcaagtg attctcatgc gtcagcctcc 71760 aagtagctgg gattacaggc gcccaccacc acgcccagct aatttttgta tttttagtat 71820 agatggagtt tcaccatgtt gaccaggctg gtcttgaact cctggcctca agtgacccac 71880 ctgtctcagc ctcccaaagt gctgggatta caggcataag ccaccacacc cagccaaaaa 71940 cattcttat aatgatacaa gtaatatacc agacaagaaa ttactcagtg tactatgtga 72000 gattaaaaaa aaaaaaaaa aaagactgga agtggaagtg ggagtacttc aaattcttgt 72060 ctgatgaggt aaagatttta acttggtgga aggaatagaa atcaaggatg tgagaaattt 72120 ttcattaatt agaatttcga gattcttctt ttaagaatgc agtgatgcta gtgaagtggt 72180 tgagtgaacc atctttcagc taacaattat aagatctgga caaaatattg aaagaaaaac 72240 tttaactgtt ttaaaagcca tggaaagtaa ccaaaaaagc aaagccagat gagagcctcc 72300 aactgcaatg tgtaattgta tgtttgtggc tttcttgcct tatggtgcat tttcgcctcc 72360 tgtctttcag tggcatagga aagaagttac gggtagcctg gcagttggaa atttactcag 72420 gggaatcatg gaagcaataa gtaagatcca aaatctgagt gtaaactctg tccaaatcat 72480 ggctaatcac gaaactatac atgcataggg gagaccccag gggacccagt gtaaaaacag 72540 gcagaaacaa gagcggaatc tgctcctgaa agaattgaac cctgtgagat ttgtgattgc 72600 ttcttttttt gacagtacat ttctcaactt gcatgcaatt tgcgtggcca acagctggct 72660 tgaggtatca gagcacagaa catattgttg acagaagagt taaaatttag ggaacaaaca 72720 ctgaaagcaa gataacatca gaggatgtag gccacacatc tcagtataat ctctgcccat 72780 ttccttcact gaccaccaga ctacccaggt gcagagggga tgccctgggc atcaggttag 72840 aagaaggaag cagctggaag gtgaaagaac taagcaaaat cattgttgct tactataagg 72900 gagacacaca gtaagtcctc acttaacatt attgataggt tcttggaatc tgactttaac 72960 tgaaacaacg tataacagaa cattttttc tcatcagttg tataacaaag cagtgttaaa 73020 ggaaacgaca gtattcaagg accttgctgt ttgtgttttg cttcaagttg ctgtttccaa 73080 gacctatcga tggtattaag tgaggactta ctgaagttttg cagtttgagt ccatacgagc 73140 ccattagaat catacaacat gaaaaccaaa tggtcctttg aaagattgcg acaaaatctg 73200 gttgctataa cttgctattt acaatgtgta ttttcaacta aaaattatta gatatgcaaa 73260 taaagtggaa atatgactca ttttcaggta aagaaaatca ttcaatagaa attaacccca 73320 agtatagcca gatattggat ttagcaagca aggactttaa atagcccta aatataatca 73380 gaagaattta aggagtccta tgttcaaagg attaaagaaa aatacagtca cccctctgtt 73440 tccatgtttc tgcatttgca gattcaacca accgtggatc aaaatatagtt gggaaaaac 73500 ataataaat ttacagtaca gcataaaaa atatgccaa taaaaaaaa taagctctg 73560 ttcagtgaat agataggaga tcaaacaga gaacagata ctgtaagaa gaagcaaag 73620 agaattttag ggttgagatc agtaactga atgaaattttt tatattat tttattt 73680 tttattttgt gtggagtct tgctccgtcg cccaggctgg agtgcagtgg tgcgatctcg 73740 gctcaccaca acctccgcct cctgagtagc tgggattaca gatagcacc aacatgtctg 73800 gctaattttt gtatttttag tagagacagg gtctcaccat gttggccagg ctggtcttga 73860 actccctccc gacctcaggt gatctgccta ccttggccctc ccaagtact ttgattacag 73920 gcgtgagcca ctgtgctcgg ccaagcaaa cagttgtttg gagatggcaa aagaatcagt 73980 taagataga taaaaag tcatctattt gaagagaaa gatgagaa aaataagcag 74040 agtttgagag acctttgggg taatacaatg tttgaacatg catctaaatg gagtctcaga 74100 tggggaataa atatggctg aaaaccccca caactttggt ggaagtatc atttacata 74160 tccaggaagc tcagcaaac tcaagcagga taacacaca CAAAAAAAAC gatgttagca 74220 cataagtggt caaattgctc aataccagag aatttcttga aagtagccag aaatatctta ccagaaacaa tggcgacctc tagccatgga tatggtatat tcagctgaaa ggcaaaagc 74400. 74400. 74400. 74400. 74400. 74400. 74400. 74400. 74400. 74400. 74400 aaaccaaaac tgggaattt tcaccagcca gccaccattg caagcattc taaggatc aatttcaagg gaaatggcac cagatggcaa gtaccatcta caggagga tcaacatcaa aactgtaaa tacataattt actctaattt tttaaacta tattttcct tattttaaaa acaagtacct gtgacttgaa gcaaaaatta tgatgctgta ttgttgggtt tataatggag tttgggaatt tacatattgt acaattttta atatgtaatg acatacaaat taacgtgtta atagtcttct aacttatgaa catggtatat ctcattaagg ttattgttta attttagtaa tgtatatag gtttctaaaa aacttaaaa tgtggtaaaa tatgtacaaa ataaaatttg ccattttagc tgtacaattt ggtggcacag ttgcattcac agtgttgttc gttcattact actttttcca gaacttttct atcattccaa acagaaactc tgtacctact aagcagtaat 74940 ttcccatttc ccttccccga gtctctggca gtgtctaatc tactttctgt ctttatgaat 75000 ttggctattc tgtatttcat atatagtagt cccccttatc cacagttttg ctttccacaa 75060 ttttggttat ctgtggtcat ccatggtctg aaaataggtg attatagcac aataagatgt 75120 tttgagagac cacattcata taactttatt acagtataat tgttcttttt tattattgtt 75180 gttgttaatc ttttactttg cccaatttac agattaaact aataagtata tatgtatagg 75240 aaaagacata gtatatag agtttggttc tatctgtggt ttcaagcatc cactgggggg 75300 tctggaacat atgctctgtg gataagtggg ggactagtgt acttcctgcc ctaccccttg 75360 gtttggagtc gctgctgtat gaatataagg gcagtctgcc tgtgatgtga ctctccattg 75420 atcacctggg tgtatgaatt aattgctgtc tataaagagt cttggaatga ctattgagtt 75480 tgctctgtgt atgtatacat acaacagtat ggctactgtt gtagctgatt tggctatgat 75540 actgtagtat cttatttgct ccaaagagat ggagtagtga tgaaatctgg tttactaggt 75600 ggaagctagt gtaaaaatgg gtactctgtt ttattgaatt agcttgattg gaaaaagtga 75660 agtgctgatg gttttgaaaa tatgatgata atgatgtcat ccttctggtt taaatatttt 75720 gtagcacttg tggtagattg aatgctggtg tcggtagtaa agtcatgctg cagttagtg 75780 ctgaaccagc tgtactgttt tgggtagtaa cttagacagt agagaacacc acttttctag 75840 gcagggctcc tcacctctcc tagggggcca tttcactgca tcttggagtg aatacaga 75900 gaggaagtag ctagatccta atttctacaa gttatatcag ttggggaaca gttgtggttg 75960 tcaacctgtg ttagggctgt attggttttg ctttcagttg tgctataaag tggaaaaaat 76020 tgaattgttt attatctct tattgtgaaa cttcctgtg gcccatagaa gtggcatagc 76080 aagctgaaca tagctgggtt tgttcttcat tgcaagatcc tacccccacc tccctttctt 76140 tcctgcctgg tttcttgtgt ccatactgca agctcttttt cccagttaga agtaagttag 76200 ttcactctta atagagctga tttacaaagg aattttatgt gtgtcatact gtttgattct 76260 ctgaaaggta gatatgggac tgtggtaaca atccagcatg atgttaactg tgctctcatt 76320 tttaaatgtg caatggatg tatgtgaat ggtggttgt ctgatacaat attggctgct 76380 aagacatgtc tgacctagag cctagatgtg ttggctctt addaatgctg gatgatgtat 76440 atctggatca ttctttttaa tgactgaga tgatgcgtat cttctacctc ttgagagtta 76500 ggaatgtaaa gggcaagtga aaatttgtt agatgctctt aaagatgaa atagatgtg 76560 ctccatcact agtatagttt ctttttgacc actatgtcaa cctgtttaga aagtatattt 76620 taggccgggc gcggtggctc acgcctgtaa girl tggggggc tgaggcggc 76680 ggatcacgag gtcgggagtt caaccagc ctggccaca tggtgaaacc ccatctctac 76740 taaaaataca aaaattagct gcgcgtggtg gtgcgtgcct gtaatcccag ctacttggga 76800 ggctgaggca ggagaatctc tgaacccgg gaggcagagg tgcagtgag ctgagactgc 76860 accagtgcac tggcatggca acagagactg ccacagagc gagactccat ctcaaaaaca 76920 aaaaaaaaaaaaaaaaaaagt atattgtaaa catcaatta aagaatttc 76980<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> ctgaagtaac tttttttttt tttagtaggg gtggggaaga tatgagtaga agagaaatga 77040<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> attggaaact gagtaccact accctttttc ttaccttcta tccagaaatc tttcttaaat 77100<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> tccacagtat cagtgtaaca tcttttatct tttgagctgt ctttgagatt ctttactttg 77160<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> tctccagact gtttgttagg attctactag agaagttgtt ttcagatttt aatttctctg 77220<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> ctccatttta atcttctaat tttttaatga aaaaaaatcc agttttattg agttcttttt 77280<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> tttttttttt ttttttttgag acagagtctt gctctgtcac ccaggctgga gtgcagtggc 77340<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> acgatctcag ctcactgcaa gctccgcctc ctgggttcac gccattctcc tgcctcagcc 77400<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> tcccaagtag ctgggactac aggcgcctgc caccacgccc agctaatttt ttttgtattt 77460<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> ttagcagaga tggggtttca ccgtgttagc caggatggtc tcgctctcct gacctcgtga 77520<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> tccgcctgcc tcggcctccc agagtgctgg gattacaggc gtgagccact gcacccggcc 77580<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> tattgagttc taattaatgc ataatttgtt gagttttgac gtatatgtgc actcatgaaa 77640<h2 style=";text-align:left;direction:ltr"> ccatcaccac aatgtatata tccagtgaat atatacatca cccttaaaag cctctttgta 77700 atctcttcac tccccacttc gcaggcaacc actgatttgc tttctgttac tgtaggtcag 77760 tttgtatatt cttgaatgtt atgtaggtag aatcatataa tgtgtctcct cttttgtctg 77820 acttctttca accctagctc aatatatttg agatttgtct atattgttgg atgaatgatc 77880 aaaactttgt ttttgttttt ttaactgggg aatagtattt catttttagt atatagtaca 77940 atttattttt tgcccatttc catttagctg ttattgctgg attgggttat taacagttat 78000 tgactattat gaataaagtg gtcacaaatg ttggtgcatg gttttttatg tggacttgtg 78060 ctcttatttc tgctatgagt ggaatggctg attcatatag taggtgtatg tttacctgta 78120 taagacactg ccaaactttt ccggtttgta tcagtttata ttaccacttg cagtgtatga 78180 gcattccagt tgcttcacat cctcagaatt cttggtatgg acagtatttt aatttgattt 78240 gttttagtag ctgtataata atgtcttatt gtggcattca ttaatcatta ggaaaatgcg 78300 aattatgttg aacatcttta cctatgcttg tttgccattc acatcttttt ctgttgaagt 78360 attttctcga atctttgctt attgatttat tgatttattt attttgagta agagtcttgc 78420 tctgtctcct aggctggagt gcagtggtgt gatcatagct cactgcagcc ttgaactcct 78480 gagttcaagt gatccccctg cctcagcctc ctgagtagct gggactacag atgtgtacta 78540 caacacttgg ctgttttttt tttttttttt tttttttttt aaggattttt ttaaagagat 78600 agggcctgac tgttgcccag gctggtctca aacttctggc ctcaagccat ccttccactt 78660 cagcctccag aagtgcaggg attacaggct tgagccacag tgcctaaatt ttttcattgt 78720 attgtttgtc ttattattga attataagag ttctttctat gtgctaaata ctagtccttt 78780 ggataattac ttgcagattt ttttcagttt gtggtttgcc tttttttctt tacccatgtc 78840 ttctcaagtt caagtctttt attttgatga atacacattt atagtttttc ttttatattt 78900 catgcttttt gtgttgtatt ttggcaggcc aaataatgac ccctgaaaga tgtccatatc 78960 ctaatttcca aaagctgtat atatgttacc tgatatggct ccacaaactt tgcatatgtg 79020 attaagttaa agattttgaa atgaggagat tagccaggat tgtccaggtg agcccagtgt 79080 aatcagagag tccttgtaag aaggaggcaa aaccaatcag ggcagaagag atgaatgact 79140 gcagcagagg ttggaatgat gtgctttgaa gatgaaggga aggggccatg agctaaggcc 79200 atgagataat aaatttgtgt tgctttacac caagtttata gtaatttctt accacagccc 79260 atatagattt tgcctgtaag tggaatgccg ctgtaacaaa tacctaaaaa ggtgaaagtg 79320 gctttgaaat tggggtattg gcagaagctg gtagaattttt gaggaacata atggagaaaa 79380 cctagattat cttgaatgta cagatggtag aaatacagat gttaaaggct ctgctggtga 79440 tgccccagaa ggaagtgagg agcacagtag agaaaatgtg tatcgtctta gagaatacct 79500 aaatcatcat aaagagactg ttggtggaaa tgtgaacatt aaaggtgctg ctgcttgtga 79560 gtgctttgaa ggaaatgagg aagatgttat tggaaactga agtgaaggag atccttgttt 79620 agattgtaac agaaagttta cctgaattcc gtcctgtagt tatgtgacta actctcctgt 79680 gttgcctggg tatagcagca atcatttata catacatttg cagttctgtt ctgtacttgt 79740 tataaagtag ttttaattaa agtgacagat ttatgtttt ataaattaaa tttatatta 79800 aaaaatcagt atttagaaca aatatcttag tggactatat tcttgagata ttatattata 79860 agtcttttta cagcttcctt tcaaataaat ggatatgtaa tttaaacctt taatttctgg 79920 atttcctgat gacttttctt taaaaagaat aatttttaaa aacacatttt aatttataac 79980 taaaatggtt atttaaggaa acacatatat tagttttat tagatatg cttttttatt 80040 attaatttgg aaagtggagg tgcattgttt ggtagaataa ttttaaatgg tagctcttgt 80100 taatggctaa tatttattag tggatacaac ttacaaatat ctgtacattc agtctttatc 80160 cttatcttcc atatcttttt cttctgcatt ctaggttttt ttgtttgttt tttggaagga 80220 ggatatataa agtaattat actacatttt tagctgttgc caagttgaaa gtcagtgttt 80280 agtttttttt aaaaagggct atttagtgtg gaattcctaa atattatagt tccctcttct 80340 gtcctttcag agctattgca ccctgttaaa ttttttttgc attcagttca accagtgttt 80400 gaaaattacc atagactta aagtacttct ctgaagttag aagagctcct atgtctgatg 80460 ctatattgct agtatttcta ttcaggttgg aatttggaat agtcattatc aaagttatt 80520 tgtaggcaaa agaaaaaaaaaaaaag ttatctgtag gaatattgg agactggggt 80580 aaggtag tgacacagtg aaggcaca ghaatttca gatatgaga cacctacat 80640 ggtttctgca aggtattggc gtggaaaaaaaaaaaaagg gggggggggc ttagagagtt 80700 actctccagt aaagagata tagaagcag tactatagtt atacaag ggtagttctt 80760 tggattctgt ttagatcaaa ttaactagaa atacatttt tggaatttt 80820 gatattgac tgtattact taatatcgtg gaaatact tatttgaat gtgtatagtg 80880 actttgtgag tatgaaaggc agtggccaaa ttatttagtg atacataatg atgtatatgg 80940 atgagggag taatgacgtg atgtctgaa tttactttaa ataccttgg aaaaaatgaa 81000 taaaagatag ataaagcaat attgctaata ttcagtacc tgttaaatat aggtgacagt 81060 atatatatag aggttcatta tactccttc tccacgtttt gaaaaatttc atttaaaaat 81120 tcaaaaaaat tctaaaaaat atttttctt ttagaaacta acacatgctg aaaaaattca 81180 aattttgttc actgaccacg ttttgctgc caccactctt tcaacattta aaaaatgttc 81240 ttaaatcttt aaaaattcga tttacatttt cattaagaaa atgaggcatt tgctggccat 81300 ttcatccttc ctcttgtatt tttctcctt acctgctgcc accgtttact agaaaaatat 81360 ttctcttgtt ttttctgtac cttctccttg aaataaaa gttcagtgaa ggcaggagag 81420 attttagccc gtttttgtat ggctgcatct tccttatcca tacctgcata gcatgtggta 81480 ggtgctgagt aaatttga atgactgaat gggtgactga atagactgaa tgaaccagag 81540 ttgtagaaga catggggtga cgtggggttt ggctaaggac agaaccaagg agaacccctt 81600 tgaaaattca ctctgtggga tttacagggg aaaatgtggg ctactacata agaaattaag 81660 ataagaaatc atctttcctg tttgactgta aagccttaat atttcaagca tttaacatat 81720 tctcagcata aataattaag ttttttctt cttttttctg aaacagtctc actctgttgc 81780 ccaggctggga gtgcaatggt gcgatcttgg ctcactgcaa cctccgctc ccaggttcaa 81840 gtgattctcc tgcctcagcc tcccgagtag ctgggattac aggcatgtgc caccacgcct 81900 ggctaatttt ttgtattttt agttgagacg ggggtttcac catgttggcc aggctggtct 81960 caaactcctg acctcaggaa cccacctgcc tcagcctccc agagtggtgg gattacaggc 82020 gtgagccact gcgcctggcc agtaattaag tttttatact gtaagttctc taattgtctt 82080 taatgtattc ttgaaagtgt tttcctccta atttatttat tactgcaagg caatccgttc 82140 ttgaggttct atttaaagtt tatgtatttc ttctcaggaa aaaaaattac ttaaaactag 82200 tggtttgtac agtcaagatg agttttagaa gctgttctta taatttcttt ttatgttaaa 82260 catatataat gtcacatttc ccttttccta acaactgatc ttctttcttt ttcaacgtgt 82320 atttataagc tagattttta aattttgctc cagggactgc tgtagttgtt ctactactta 82380 aaaaaagaaa gatgttagta ttgaacacta ttctgagaca cagctgataa caattgtgct 82440 caacaatgaa gatggctaaa aattgggttt taaaaataac agtgaaatt cagaagcatt 82500 ttatacttgc tattctaag tgagtatttt tctaatctct gctttaaaat tactgaagtc 82560 cttttaatga ccaacgctgt atttttagga aaaaatgtga gcaagattt ttagtgattc 82620 taaatttgtt ttgctctg gatctcttta aacttttaa aattattgaa gaccccaaaa 82680 agctttgact tatgtgggtt atctctcttg atatttacc tgttagaaaa taagctgag 82740 aagttttaat agttttcatt tattaattt atttaaaaat aacagctaat tacatgtttta 82800 cacaattaac aaagtctggc ttacaggaag acagttggat gctcatatct gcttttgcat 82860 tcagtttgtt aggatattac atgctctata ctctgacaaa aacttactt tgtgtatact 82920 cavagacag agtaaaaaac ataagtaca tcttagtatt atagaata ttttgatctt 82980 agaaactcca tgtaagtgtc tcaggaactc ccaggttca tattttgaa attgctggag 83040 tcatctctca gaggctatgt gtgacaatg gtgtttta atgaacaat aatttttaaa 83100 atagtgtc aattggctaa gtttttttt gatacttttttttttttttttttgag 83160 acagggtctt gctctgtcgt ccaagctgga gtgcggtcac agctcactgc agcctccacc 83220 tcctgggctc aagtgatctt cccactttag cttcccaagt aggaagtagg tgggactaca 83280 ggcaagtgcc accatgcctc agtaattttt gtatgttttg tggagacagg gttaccatg 83340 ttgcccaggc tgctctcata ctcctgggct caagcagtct acttgcaccc aactcagcat 83400 ccagagttc tgggagccgg attcttattt gatacattttt tacctttagg ggaactataa 83460 aaattagctt atgcttattt atgcaaataa atttgagcat tgaggaagga tgtctcttgt 83520 tcagggttgt gtttgtagat ttcacatctt ttagactacc atttaagaga agtgatcacc 83580 ttgtatctta aggaaatgaa aatcatttga tagaaatgga ttgttaaata tttttaaaac 83640 aagttttgac agttacttgc aattaaaggg gaaagcaact ttaaaatgca ttagttaatt 83700 gaagaaatac tcaagatcct taattgttgt tagtgagcaa gtattaatgt tctttcctct 83760 ttgaaaacgt atctgtacct agacaaagtt aattataaac tttttcataa acaatattat 83820 gcttcttttt cttctaattt ttaaacctta tctttgttgg tttgccttcc agctccatct 83880 atctgcaacc windows catactata catcaatta gctgatgtgg aaggaaatg 83940 aaataatg aaatacgtc atattgctta tactctagt tatattaat atagatcca 84000 agggatattg gtgtggggga cgaggaggaa ggaacattgc aagtcaagct atttcacaag 84060 tattctatac ctttgaatct tttatttcat agttttcttt agaaacaata gtgatgcaga 84120 ctgaatagct agtagataa ctttcattaa tagcagtag gcagggattt ttaattgatg 84180 cttgttgta atattagaca catgatttat ttataggctt tttattagaa aactaataca 84240 atatcaaat tgttatggac aggttataca ttttttggca acacaaatcc taccaggtttt 84300 taatgcctgg tacttgtttt tacattagta tgtgttatta atttttcat tactactct 84360 agcttcccta gcttacccat ttgctaggag tacatagcag cactaggaca ttttcgcta 84420 acgtggctgg catgcatctg aaagtgtgac agagcagggg tatagctaga tttagaagt 84480 tcttttgctc atttagaaa cttaaacttc agatttgata gtacttcaga ttctacataa 84540 tgtgctcttt cgatgaatag ctgtgtagca gcagcacagg aaaagcagag ttcttggcaa tacccagttc aattgcatct gcagatgagg atttaaaatt ctgtgcagca gacagtacct ccagcaggcg agtaaaaggt tactgcatta tttttcttgt ttgttaccat agcctttatc taccaaagga tttttaaaaa attgaatgtg aagtgcatgc ctgtttttag atttctgga 84840. aattgattta agtataacat gaatcaaa agggcagtgc aaggtgaagg cagaggcagt gctggatctt tttagcttta aaccaggga gaattgagc atgttacata cacaaagag aaacctttca gtgtcacaga caatgggaag ttttaaata cgtattttaa ttcaaggtgt ttattatta gttttagact atcttcccca aaaagggtgc tcttacatta gcaatcattg gtctatgaat gttcatttaa gttacagtaa tttgaagtat gattatttgt gaagactata aagtatttgt attack ccctcccttg tcctggaat tgtaatgtgg attackca ttgtataac aatacctttt gtgcattatt ggcaaaggta gaatgcttaa gtataaagg tatagtatag ctagcatact taatattgtt gcttatgttt tcagggtggt ttgtggtttt 85260 taaataatc ttttaaataa aatgcagaca agtaagtggg agaaattca gtatcaaaac 85320 aatgaggttt ttgatggctt tttacttgtg gtcagtacct acctatatag ccatatgtcc 85380 ttttttctca ttaaaactct tctaacattt atgatagcag gagcctcctt ggattatcca 85440 gcttgtttat tacatcatta tctgcaccag tatttttgct atagattttt attgttcatt 85500 acttctcaag tctacataaa gtatccagag ggaatttttg cttgtatatt ttatcagtt 85560 accctcctac cctcttccat cagtcctcaa agatttgtat tagctactgt ctacattttg 85620 tttatttaaa aaatacttag gcctatattt ttgtattgta gattgaataa taagattgaa 85680 aacaattctg taaattaatc tatagtatag aagtaaaatt tgttgattat tcttactgtg 85740 agtatttggc aggcttcttg aattgtagag tcataaaagg tcagcagttc tgattggtaa 85800 gttaaagaat ccatccagta atttgctccc tgttgtttct caaagcaatg cagcagcagt 85860 tcttttccag atattaaacg gttcttgaac agtgtgtgtg gagacgggga ggggtggagc 85920 tcattcctgt tggttgttga aatcgtgtgc atttacagag ggaacaggtt ggataggctg 85980. agctgaagga gtaggcaaac agatctaaac tgatggaaga cagaaagtgg ttagtataat tttggggtgt cttgagtttg ctcctttgtt aagtacttgg gctttaat aaaacaattt aaaatattaa agcaccttac cttctttcta aagagtagct gggagacttc tgttttaata tccagttttt cttggcgatg agtttgtggc tggcatcttc tgtagcaaag ctgttgtttt 86220. attctttttt agtagttt ctttcagcca gagagctgca gaatgaggca gtttgacaat 86340. 86340. 86340. 86340. 86340. 86340. 86340. 86340. 86340 gcaagtcaat gtgtggctgt ggctgcagca ttattctctc tttaatgaag aggttgagcc gttcgacctg ctgctccgat ttgttctctt gtagccatac atcagaccag ttgcagagat 86460 86520. 86520. 86520. 86520. 86520. 86520. 86520. 86520. 86520. 86520 atgcaatga aatggatgca ttatgacta gaccaatga ttaaaaata aagaccaatt aaagatgttc ttagcagttt tcttgacctt gcagtagata tccaatatca ttttgtcatc atcagattgt gtagcaatgg aaatgcactg cagtaattga ttttgtaata ggatcaggtg 86700 atttactagc tgcactgaca accacttgct tgcttgctct gagctgtgga gcactctaat 86760 ggatgttgtg atttcagcct ggagtttatg tgagactgcc ggccacttaa agcagcagca 86820 cttattttaa agattagatt agtttttctt tcttgttttc ttcgtttcaa gttttgtgag 86880 tagcctcagt aactttatgg ttaagttgta tgccttcatg aaattttaga gattatatat 86940 tatttcattc atcaattcat agtctttctg ctccatattc ctagctaaat atcaacatat 87000 tctggtattg accatgagag catatctcta aaatatgaga gttattggta actatgctgt 87060 gttatctaaa tgaagtggaa tattcctcac attcgtagat ttcattagct tcagactcta 87120 gctgtaatta gaatgatggt aaggttcttg atctcttgag ttgtactgca gttgttttgc 87180 atcctttttt ggtcttttac tttcttagtg gtttcatggg taaggcacca tttaggaaat 87240 atgagttgta ttacttctaa gggatactga tgaggatata taaagctatt ttaaagtagt 87300 gtttaaggat atagcaatt aaaatctaa tatcaagtat tataaatttc aaagtgatta 87360 ttttaaaata atttttgtt tccttttctta tgccttttaa acaaatatt ggttcaaata 87420 taagtgta ggaatattgc taactgtaaa atagaactac tgtcatagaa actcagatgc 87480 tgtcaaagac tttgattact taaaagtttt gctgatggtg ttagattaga aaagaaactc 87540 tcttccactc ccttcctcac caatacctct acctcatgta aagtgtttta tacagactcc 87600 accacataaa atactgaat tctttatcat tccctgtttc tgttcttgcc atgatagaga 87660 caccattct ctcaccaca tctaaaaaca tttacaaaaa ttaataaga ttaacaattt 87720 actgtagtag aaacggggca taaaattgtc atcacatgtg gtattcaaat caccatgtta 87780 agagaacttt cctttttgat gtactcaaat agtcacttgt agtgtttgaa gccttagtgt 87840 ttctgaaag ttgaaaatat tatctgtgct agtctgcaca ttctctta ttcagatact 87900 ttaaacatta atttaggaaa attgaaaata atttaacac tagtatttgt aatcttttat 87960 tattcacag gtaaaagtt tatagactct cttgacttcc aaaaaaaa cccttctgtg 88020 aacactgatg aacataagca tgttaatatc atttaggatt cggtcaagga tgtgtctgaa 88080 tttcatatat attgaaaatg tttaatgatg ggccaccagc aaattaatca tggatatgtt 88140 ttactggagt gccgtctatg acagcttctt ttcatgatgg gttcagcaaa taggaaacga 88200 ggaagtaaac accagagtgt tgactacttt ttataaaagt tagaaagata actatgattg 88260 gtctgtgatt agacagtatt ttatgtaaaa taaatgggca gcgtgaagtt ctagcctcag 88320 tggagctgcc ttttctaaag agccctggat cgagcattaa aagagttgga tttaatttgg 88380 ctctgccatt aatctatttg ataaccttga tcaaattatg tatgaacatt ttaaagtccc 88440 ttaaacatgc tcttaaaatg tccattaaaa agatttcaat ttacccttac cagtgggaag 88500 tattagaata cttgaccttg aagctataga agttagagtt aggaagaagg atgaagtttc 88560 ttaaagaatc aagttgtagg tgatgttaaa acctctcctt tcacttttta tgtcttttt 88620 tgggggggtg ggtgggtaac atgtttttgc taagaatact gttttatctc tttgatatcc 88680 aatatttcct aagtaggata gtaattctgg aaattatcct agtggttaat agaatagacc 88740 tgggattaaa atctggtgct gccaattttt tctagacttt ctaacaaaga taatgtcatt 88800 agggagttta ttcagtacct aggatatttt ttagtaaaca cgttttaaga aggttggcca 88860 ttatgttatt ggtgctttct tcctgtatgg cctattagat aagcgctgtg cagtcatctt 88920 tgttgcctag gcaaaatggt ttgtaggttc attgattgaa ctcttacttt ggaccaagtg 88980 ctgtactaag cactttggtt tttttttttt tttttttttt tttttttttt aaagacagag 89040 tcttgctgtg tcacccaggt tggagtacag tggcgcgatc ttggctcact gcaacctctg 89100 cctcctaggt tcaagtgatt atcctgcctc agcctcccaa gtagctggga ttacaggcac 89160 ctgccaccac acccagctaa tttttttgta tgtttaatag agatggggtt ctgccatgtt 89220 gcccaggctg atctctaact cctggcctca agtgatctgc cccgcttggc ctcccaaggt 89280 gttgggatta caggtgtgag ccactgtgcc tggcctgtac taagcacttc tatgttaatt 89340 atgtcattta tgagaaagac tctaatgatt atttttaaag atgagagaac tgaagctcag 89400 agaggttcta caactcctaa aaatcacaca actgggaaat agcagaacca atgtcaaaac 89460 tttaggcatc agcctgctgc tcaaaggaag tgctcattga agcgcttcgg atttgaaat 89520 ttctgataag tataatgcaa atatttttta aaaatcccaa atctgaaaca tttctggttc 89580 caagcatttc agataagaga tactcagttt gtatttgtac tttcaattaa gctgtgagtg 89640 tagagatgaa gccaaatttc atctgaagat gtaatataaa tgattaccta attttttag 89700 tcttgaataa gaaatgattt gttcacctct tactcagcaa taattcgtag gaaaaattat 89760 tcatataaag catatttgta ctatttggag taatgttttc caaagtgtgg ttcagggctg 89820 ggcacggtgg ctcacattgg taatcctagc gctttgggag gtagaggcag atgggtcgct 89880 tgagtcgaga agtttgagac cagcctggga cacgtggcaa aacctcatct ctacaaaaaa 89940 tacaagaaaa ttagccaggt gtggtggcat gtgcctgtag tcacagccat gtaggaggat 90000 catctgagtc tggcaggtcg agactgcagt gagctgagct attattgtgc cactgcagtc 90060 cagcctggac agcagagtga gaccctgtct siaaaaga aagtatggtt caggaatcac 90120 ttgtatctat cactttggat ggtggttaaa agtaccagtt tacatcaggg cacattgaaa 90180 gatcaccgg aatgggatcc agagatctt gttttaat aagccctca catgattctt 90240 ggttatacca aattgttaca accaatgata ttgagaatgt tttcctgttt taccttgttt 90300 ctatgccttg cagctttcc tttaagaatt tgtttacaaa ccatagatgg ttgtaaaat 90360 tatccttctg acttatggtg aaatgtaaat tggttcttt gtgtactca ttttaggaac 90420 ttgtttagga ttaaaagtat tcataaactt tgactcagaa aacctacttc taggaattat 90480 agatatt cctaggaga tactcagatt cgcaggaga cttaggcaca aggatgttcg 90540 taccattatc atctataatg gtgaaaaact ggaacaact caatttcaa catcagataa 90600 atggtttgtt ttttatatcc atttgttttgg actaaccatc cagccataaa atgttatatg 90660 gggaagattt tgtaagacat aggaagtgc tcatgattta atgtaagtc tcgaagaata 90720 taaaattatg gtcatacata tatgtacata tagtgcatat ggtcttaggt taaatcatat 90780 gaaattaccg ttttgtagg tcaagagtag tagaatca gcatttcat gtagtgtaac 90840 ctaacatggc acccattttt aaagcacatg tttgtagaga agcacatgtt tgtagagaag 90900 cacatgtttg tagagaacgc tttgtagaga aggagctgga aggaaataca gcaaatttat 90960 aaagtgatta tctctggatg atgatattat ggataatttg aaatttca tctttacatg 91020 tcttatgttt tcaaatttc tactatacct tagactcaac ctttgaaata ggacaaagta 91080 attaataaa acagggaaca gttgcaaact ttctctgaaa aacattaaaa ttttttagaa 91140 gattgtaaat cctttaagct agtataagga ccccttata ctaatattct taactcttgt 91200 attaattatt gagtgtgttt atgcaaatgg atcatatatg cctttaccta cccacccagc 91260 aaatttgat tggattttaa tctgcagtag aaagtgtctt tcaaaagaag agaaaaaaat 91320 caattttcaa agttttaaa aagaattggg ttcttaaaag accgccaact atatgcagga 91380 gtcagttggg tagccacgtt aagcacaaag ccctgtttta ggctgtgtgg ttttgatttt 91440 taattgtaat ttaactgatc gataaaactc tgtagattaa aattagtaat ttgtgtattt 91500 atttaaaat attactgtat ttttttgaaa ggaaaatgtt tctcccactt tcatacactt 91560 taatcgttta atttaaaga aatagcttaa ttaaagtaac agctaccata ttctggttat 91620 ctgccataca ccaggttttg ggtgctttaa tatgtttttt gttttgtttt gttttttga 91680 gaaggagttt cactcttgtt gcccaggctg gagtgcaatg gtgcgatttc ggctcaccac 91740 aacctccgcc tcccgggttc aagtgatact ccggcctctg cctcccgagt agctgggatt 91800 acaggcatgc accaccacgc ccggctaatt ttgtattttt agtagagaca gggcttctcc 91860 gtgttggtca agctggtctt gaactcccaa cctcaggtta tccgcctgcc tcggcctccc 91920 aaagtggtgg gattacaggc atgagccacc gcgcctggcc ttgggtgctt tatatgtta 91980 cttctttcaa tcttcaccta gaatgtatta attagatatg agctttgttt tagcgttgag 92040 gaggcactga aactattata agctttcctg agatcatatt aagtggtgga tctaggtttt 92100 tacctcagta atgtctaact taagaccca tgttcttatc cctgatactg tccttgttgg 92160 tctgtctgaa acttttaagt gttcatact tgggaaaca aactgttgta taagccttcc 92220 taattcagac tgtcaagtg tagagcaag tatataatga gtcattattg ctgattttta 92280 ttcaactatt tgttacctgt ccttaatct gtcagtaca tgtgtactgg catttaacga 92340 tcgcctgcta atagctaacc tcttgtgtaa accactggaa atactaaac agagaagcca 92400 aaaattactt ccttggagtt tacagtccta atgagaga cagacacaa atagttaca 92460 aggtatttca gaacataggt atggaataga acctgttgga acagaagtt tttaaactaa 92520 taatgttttgg gagtagtggt gagagttac ttgggaagcc atcttggaag aggtgaattt 92580 agaaggagcc atagatttcg ttttgctac cagcctagga atttacatt taatacaga 92640 acccctgcct ccagagtgat ctgtaattct actgaagttt gagaaccacc actgtagatt 92700 gtagttgatg ctacgagaaa gcatataata ccctgaggaa gctgtgtgga gtgggaaatg 92760 agaagttgga aacctcagag storm gctttgata gtagggag tttatgata 92820 gttacgatta atatattata agcaatatct tttagtgcct agaagtaaga ttggaaatgt 92880 cttgaatttt gtataagatc acaaaactta caggaagaat atcaaaattc cgattgaggt 92940 tacttttttc tgggagggat ggtgaaatgt tattctttac cctacaatgt gtgattaaga 93000 gtgaataaaa atcgtgttaa ccttttaaag ataatgttta agaaacaggt ttaattttta 93060 aaagaaaagt gagcatagga gcaaagtttt gtaacatatt ctgcttctat ataggaaatt 93120 aattcctaaa ttttggaaat gactagttga aagtaatagc agtctatcct ccaaagagag 93180 ctttttaaaa tttatttttt agaatcagac ctgggttaac ttttagatat aatttggcat 93240 aaccagcaag tcattggtta ttcaaaaata aagattggaa ataattgcca tatagtcttg 93300 gctctttgcg tattttgtga tactgattgt tgcttctctcc tttattcca ttttattatt 93360 agagcttcat taagagtgaa ttgaaaagaa aactgaattt tattatttta aaaatctgaa 93420 tagttggatt ggggcaactt tcttcctatt tatgagactt cactcattta tgttggtctt 93480 atattgacat taaagaatca gtgtcatata ctggtgaata ttaacaaaga gacaagatta 93540 agattaaga attgaacct ttaagcagga gggcgtgtgac tatggagca atttctgaa 93600 aggcttaggg gtagagaaaa tcaaagctac tgatggtatt atagtctta gaatgatgg 93660 agattacatt ttctctca gagacaggcg aagaagg gaggagtaa gaaaaaaaaac 93720 ctttgagatt gagatatcac aagttgatag gtacacagct ctctgaaagc ttcagtcatc 93780 tcataagga gaggaacata cttagccata taagttcgag ttgctgaata tacattctat 93840 gtaggtaggt ctgtgtaatt ttgatacgta ttttctgttt atcacagtgg aaattgttct 93900 tgatcaatgt ttttattca atagaaaga tatattgccg cttccatctt aaaatttcta 93960 catagaagg acatgacgct tagtgaacgt tattgaaaa aaaaaaccgt ataacttaa 94020 gcaatgaaga agagaaaca gtgtttcaga atgttacagt attgaacctg aattggtaga 94080 gagaatagaa agtggtgtga acagtcaggg tccaaatgac attctatata aagcatatag 94140 gatacattt ggagcaggga gtgggatgggg gatgcttag attacatctc tttactagat 94200 gggtgtactt gttctgtgca aggtaccatt ttctccctt tttgttagc tcatatatcc 94260 cttcccagtt ttgagagtg ctccactggt atttatact ttagttt gatattcag 94320 gatataccctg ttcagaaaa ttcatagaag ttttaaaaat gccttgatgt aaaacaaaat 94380 ttcaggtaaa cttaaatatt ttaagtttt aaatttgt gttaccaaa ttaaatttg 94440 gttagagtttt gataccta agtgatagaa tcatcttaa cacatgttgt cacagaat 94500 ttgaatgctg aagtcaattt ttgttattgt tattgttctg cttagtgaag aaatgtatcc 94560 tctctaacca gggacagtat gtactgcttt ctccttaata ctttgagatt ttcataaaga 94620 aaataatttc aaggtgttg tgctgcaagc tawagatt atttctaag gagaatttg 94680 tcattctaat gttgtcatc ttccttgtgg cattattata aattaagaa actgaaaaaa 94740 aattttttta gagacatag tatataccag aatttaaatt tagttttggca taagaggcca 94800 catattctac ctagctatt acagctgta ttgttattg cctattttg actcattttg 94860 atatctcac tccagtcctt tttagta tttcttaaaa caaaatggg caatgttg 94920 gattgactga aaatatttt taagtgttta gtagcaataa atttaatct tttagtgcag 94980 attggtttac cccataacag cacatatgga agagtaag ccaggtctgt atgaagcagg 95040 aggtgacatt ggacttttt tttttttt ttttgtgac ggagtcttgc tctgtcaccc 95100 aggctggagt gcagtggcac gatcttggct cactgcaagc tccacct gggttcacac 95160 cattctcctg cctcagccctc ctgagtagct gggactacag gtgcctgcca ccacacctgg 95220 ctaattttt tgtattttt agtagagacg gggtttcact gggttagcca ggatgtctca 95280 atctcctgac ctcgtgatcg gcccgcctca gcctcccgaa gtgctgggat tacaggcctg 95340 agccaccgtg gactcttta ataaccata gtacaggcag ttactttgt tatatacag 95400 tatagttgtc tctgaagaaa acctgaagct ctgcaaaatc gggccctgaa aatcggtttc 95460 tgagtggctt gttcctgtgt aaacttgtaa tctctgtagt aacgaaacca gtacccattc 95520 taaaaaat attatatagc taaatatta ccccagttag ttctaagttc taggattt 95580 gctttctcct ttgaaatgta ggtcctcgag aacattcatt tctacttatg atgaaattgt 95640 gaaaactagt aaatctgatc cagggtgtag tttttatcag ttgcctctca ccccttaaaa 95700 aaaaaatta acgtgggaaa aatattgtca tggattttct atctgtactc acagcttgac 95760 cagatggtt taacattgtg gaatgcctag cagtttaaag ccattaacta gcctctggtt 95820 acccttct ggatttctag ttttttctt aaggtcatca tgtattgctt aagctctgtc 95880 tttgtgagaa agcttgtccc tgctggcttt aaaactttac tatgctgggg aaaatttgg 95940 actaaagtga cattcacatt atactgacct catcgcccaa atgatgaatg aatgaactaa 96000 tgtacactac aagaacatgt cttaatagga aagtagactg ttgtctgtag ttgtcccatt 96060 gtttatcat tgctgctact atattgacat gaagtagcag tgggtgtgca tgtttgtata 96120 ttttttctgt gctgttaaat aagtccacgc acatctccca tgtgggtagg gtagtactgg 96180 gtgatggagt aggtttacca gtaccatttg tcccttactt tacttgtata gctttatgtt 96240 ttaaataga gtgtttttgt ttttttgaga cagagtctca gtctgtcacc caggctcgag 96300 tgcagtgatg taatctcggc tcactgcaac ttttgcctct ggggttcaag tgattctcgt 96360 tcctcagcct cctgagtagc tgagattaca ggtgtgtgcc actcctggct aatttttatg 96420 tttttagtag agacagtgtt tcaccatgtt ggccaagttg gtctcgaact cctgacctca 96480 agtgatccac ctggcttggc ctcccaaagt gctgagatta caggcatgag ccaccgtgcc 96540 tggccacttt ttgttagaat tatactttg aagataccat ggatttggtt ctagaccact 96600 acaattaagc aaatatcata ataaagttag tcacaagaat ttattgtttc cccagtgcat 96660 ataaagttat attacatgg cattgtagcc tattaagtat gcaatagcat tctgtctaaa 96720 aagtgtgcat accttaacta aaaataactt tactatttat ttatttattg agacagtctt 96780 gctctgttgc ccaggctgga gtgcagtggt atggtattgg ctcgctgtaa cctccgcctc 96840 tcaggttcaa gcgattctt tgcctctgcc ttccaagtag ctgggattac aggcacccgc 96900 caccacaccc ggctaatttt atatttttag tagagaccgg gtttcaccat gttggccagg 96960 ctggtcttga actcctgacc tcaagtgatc tgcccacctc tgcctcccaa agtgctgaga 97020 ttacaagcgt gagccatcgc gcctggctaa aaaatacttg attgctaaa aatgctaaca 97080 atcacctgag ccttcaggga gtcacgatca ttttactgct gtagtcttgc ctcagtgttg 97140 atggctgctg actgatagag tgatgttgct gagggttgga atggctgtgt cagtttctta 97200 aaataacaat gaagtttgct gcattgattg actcttcctg tcatgaacga tttctctgta 97260 gcgtgtgatg ctgtttgata gcattttatg cagagtagaa cttctttcaa aactggaggc 97320 aatccttca aatcctgccg ctggtttatc aattaagtgt atgcagtatt ctaaattgtt 97380 taactttgtc tcaggaaact actttccttg ctcattcaga agaaacaaca ccttatccat 97440 tcaagtttta tttgagatt gcaacagttt agtcacattg tcaaactcca gttctaattc 97500 tagttctctt gctatttcta cgcgcctgca gtgacttccg ccactgaatt tttttttttt 97560 ttgagatgga gtctggctct gtctcccagg ctggagtgca gtggcacgat ctcagtcagc 97620 tcactgcaac ttgcgcctgc cgggttcaag tgattcttct gcctcagcct cctgagtagc 97680 cctccactga agtcttgaac ccctcaaagt catccacgag ggttggaatc aacttcttcc 97740 aaactcctgt tgatgttgat attttgacct ccttctgtga aacacagata ttcttaatgg 97800 tatctggagt gcagttatcc ttctcaaaag gttttcaatt tactttgccc agatccatca 97860 gaggattcac tatgtatata tataaaacag ctaatgtatt tctaaaacaa gactggaaag 97920 tagaaatgac ccttgattaa tgggctgcag aatgggtatt gtattattag gcatgaaaac 97980 aacatgaatc tccatgtaca tctccatcag agctcttggg tgaccaggtt cgttgtcatt 98040 gagcaatgag taatatttga aaaggaatctt tcattctgag cagataggtct caacagtggg 98100 cttaaaatgt ctagtaaagt cttgcaataa atggatgtgc tgccatctag gctctgttat 98160 tccatttgta gagcacaggg agagtatt tagcctaatt cttaagagct ctacagtttt 98220 98280 agagtcagcc tgtcctttag tttggaaggc aggtattgac ttcacctgtc cagctagaag 98340 agtcatggat ggcatcttcc agcagggggc tgttcatct acagtgaaaa tctgttgttt 98400 agtgtagcca ccttcgtcag tgatcttagt tagctagacc ttttaggtaa cttgctgcag 98460 cttctgcatc agcatttgct gctttacctt gtacttatat gttatcaaga cagcttcttt 98520 ttttaagccc gtgaaccaac ctctgctagc ttccagcttt tcttctgaag ctttctcacc 98580 tctctcagcc ttcatagaat tgaagtgagt tagggccttg ctctggataa agctttggtc 98640 taaggaaatg tttggttga tttgaccttt tattcagatc actcaaaact ttttccatat 98700 caacaataag gctatttcac tttcttatca tttatgtgtt cactggagta gcacttttaa 98760 tttccttcaa gaacttttct tttgcatttc tagctttga tttaaagtga gactcttcct 98820 ttttgcctga atgcttagag gccattttag gattattaat tggcctaatt ttaatattgt 98880 tttgtcttag gggataggga ggcctaagga gagggacaaa gatgggggaa tggctggttg 98940 gtgtagtagt cagaatacac aacatttttg ccgtcttcca tgggtgcggt ttgtggcacc 99000 ccaaaacaat tacagtagta acatgaaaga tcactgatca ttgatcatca tatagatac 99060 aataataatg aaaaagtttg aaatactgca agaattacca aaatgtgata cagagacatg aagttaccac atgcttttga aaaaattgtg ctgatagact tgctcaacat aggattgcca 99240. 99240. 99240. 99240. 99240. 99240. 99240. 99240. 99240 aaaatgaggt atgcctgtaa aacaaacccg cagaaaaaaa atcgtctact cagaagagca ctgacaagta tcattgaatt attatatcta caacttgcta atcaagctaa tgtagtgtga gttgtagata caaccatttt aatgcagggg ttcctgagat ctgaaatta ttttaagtgt gcctccagtg tagaagatt gagaaaggtt gaaagtgaag atcaataatg ggatgaactg gaatatgcc tacctgataa tacaaagcaa tgagagaaac atagtatcac ttccgtcata ttcctgcctg cgatgcataa tgtgaatcca aaattagaca aaccaaatt aagggccgtt atacaaaatg aatggcttat aatctttcaa agttgttaa ggaatgaaaa taaagaaagg atcaaggaag tatttcagat acaaaactca aatgggttct to gather to cagtctgata tgtcagtgcc attttcctta ctttaacatt tatattgtga ttatgaagaa gtatgtcctt 99780 tttataagaa atgcatactt acgtgtttgg taggggatgg tgcatcatgt tggaaacccc 99840 tcccctcccc tcccctcccc tcccctcccc tcccccaggcc tctcgttagt agtttccaaa 99900 ccttttgcat gctgaaccca ttgctcaaat gaaggcagaa tattaaacat gtaaaaggaag 99960 agcttgtgtg tgggggggg ggagcgggg gaaggaggt tgggggaaca gagaattagg 100020 aacccctgag tgactacaga acttctgaaa accactgttc tgtaggataa aatctaaact 100080 ctgaagcaca ttatacaaac ctctatctat acacatcagt ttgtctgaaa ttgtatattt 100140 ctcaacaata ttgatctatt tgtatttcaa tatgttgtat gctctcatat gtctgtatct 100200 ttgcaaatga tattttcttc tctttaacga ttttgtctt accctgctgg taggaagtc 100260 accttccctc tcccttctgt atatccttgt caaggaacta tggaaattga atggcatagg 100320 tcttgataca agaacctctc ttttctcttt ataaaaaagt cattaaatag tggtggaaca 100380 ttcaggagaa agttggggac atagagacta agaaggcaat gcagtattat taggacaggg 100440 ggtaaactaa ggcatagagg acagatttga tgaacatatt atctttttta tatacattat 100500 aagaagtaga aggctagaaa agtgaacatg cttgctattg cacgtctcac tttccaattt 100560 catgaagaaa gcaaaaacta cttctacttt attacttcttt tttgatgtta attggtacca 100620 catagcaagt ttgcattata gtactgagct ttaaaatgca aggatatact catgtatata 100680 cacagacaat aaataatagg ttcttttcca cattcaggaa gtgaaactca gctgtccgta 100740 cgacacttac tgtccatata taggcatccc tcagtatctg caggggattg gttccaggac 100800 cctcacacca aaatctaggt atactagtcc tgcagaacca acatatatgc aaagttggtc 100860 ctctgtatac ttgggtttct atacccatt aatgtggaga atactttga tatgtggata 100920 tggagagctg actgtattta ttgaaaaaaa atccacgtat aagtgcacct gtgctgttca 100980 aactcatgtt gttgaggga caactgtatt ctgttacttc ctatagtttc taaaagcatt 101040 aaccaacaa tacatgtaag atgcgtggaa taatttttcc atttcctaga aaatagtcaa 101100 tcatttttt ttcagattgt gaactagaaa gcatagtgaa tatagatttt taaacatgaa 101160 aatgtaagtg tccattttaa attgttatgg atatttctgt tgctgaagt tcagactga 101220 agactactgg aaaaaatcct gtgactgaga gcacatagat tccttcttt taggtagagc 101280 gcacagtca ccatgacttc agtgtttgca tatggaagct aaaatctgtc tgagaaaggg 101340 caacaatca caggagtcat tgatttattt atttgttcat ttttaatgca aattttaatt 101400 gagtgaaaaa gtggtgaa aaacagttga ctaagaga tatgagaagg gttaatacat 101460 gagaagtcc tcaatatat tagccaccat gagatgcag attaaacca caatgccata 101520 ctactttcca tccacagaa tagctaaaat tAAagaagt cagtcaccac tgaatgttgg 101580 tgaaaatagg aagcagctga aactctctta catggctggt ggaagtgtaa aatggtacca 101640 ttcctgtgga aaactaattg acagttctt agaaaaaaca ctcacctat gagcaagcac 101700 tcctagttat ttacccagga gaaatgtcca caaataggct ggcacaagaa tgcttatagc 101760 agctttattc agaatgacca aaaactgaaa acaactcccc aacattcatc aagagaagtg 101820 ataaataaat tgaggtatat tcatacaata gaaagtacac agggacagaa aagaatggat 101880 ttctgataca tgcgacaaca cgaatatcaa aaacagtatg ctgaattaag gaaaaagaca 101940 acaaaagtaa tgcagcatga gtcatataaa catcatataa aaatgatgtt tcaaaatcca 102000 caaaactaat ctgcactgat ggaacagtag ttatctaaat gtgctaagga gtgattagaa 102060 tgggaatggg acatgagaaa agagggaact ttatggagtg atgaaaatat tcaatacctt 102120 tttctttttg agacagtgtc tcgctctgtt tcccaggctg gagtgcagtg tcgcgatctc 102180 gtctcactgc aacctgtgcc tcccaggttc aagtgattct cctgcctcag cctctttagt 102240 agctgggact gcaggcttgt gccgccatac ccggctaatt ttttttttgt gtttttagta 102300 gagatgggg ttcactatgt tggtcaggct ggtcttgaac tcctgacctc aaatgatcca 102360 cctgccttgg ccccccaaag tgctgggatt gcaggcatga gccaccgcac ctggctgaaa 102420 tattctgtgt cttgattaag gtgttgtata tatagatata tatgtttttc aaaactcact 102480 gcgctttcta ctttatataa aaagtacctc aattaaatta catattaatt gaaggcaaat 102540 taaaaacatc tctgtctgta actctcctac tgtgagtctg ttccatgttg aagaatgctc 102600 ttgtcttctt ttctttgctc ttcttggttg ggacttccct gttctaatat caggtatgct 102660 cacgttagaa agctaggaca gaggcctaga atactgattt ttttccattt caacaggcaa 102720 ggtgacagtt ttcctagagt tcacaactct tggtattcca agtcagcaca tagttcacgg 102780 tgaaacattc tctaggaggt agagagaatt gtgaccgaag aatatgatag gaccaaataa 102840 gtagctatac tagaggaag cacatttgag accactaccc taaacagcca atgactacag 102900 aaccagagaa aaccagaatc tgccaaattt cagaaataac tcagcatctt tacagggagc 102960 ctctacacaa tcacaatgag actctgaaga gtagcaagta ctgattcaaa tccttttagc 103020 tgtggactcc actctgcctc acaatcattt tagaagaggg ttttgagctt tagaataagc 103080 ccaccactgt ataaactag tgagtctgtt ttttaaggta ggattcccat cttagtaatc 103140 ataattttgg catggcaatt attaaatatg aaccacaagg agaaaaaaat gtcctcttgt 103200 tattactttt taaattaggc attttaattt catttactac tgcttgatac tctcttctct 103260 gggttcctgg gaggtttcat ttggtaagta ttgttcagta aaaattatgg gacaccattg 103320 ttttggactg tgctcctgcc ctaggcccca gtggaccaga tcaaactaaa atgtagtcat 103380 tcatgttaac tgccacataa tcaaatagaa acttccagga agcagacaga tcccaaagca 103440 gaccatttttttccctgaga acaggagatt ccagtctagc tgaatcccct gtgctttaaa 103500 cccttagaaa aagtaaactg aagtaacctg atattaacaa atcagctttt ttttcctgtt 103560 ctgtttcctt gttcccacct tacaaaaccc actgttgtgc tgttgctcag taggacctct 103620 cattctacct tgcagaatgg gggctgccct gattcatgaa atgcaaataa atgccagtta 103680 gatctgtaac taaactgttg taattttgtc ttttgacaga atgcagttaa aactcaggta 103740 tatccacact gcttttatt cgtctccttc ccatttcaga aactcctgtc tagatttctt 103800 ttcttgctct ctaaggcaaa caattaccac agttagatga atatgcctgg caatcgctat 103860 tgacagatag actctcagaa acactcgttc cattttcctt ttcaaattct tggcaggaag 103920 actgggtgga tatattgaag gaggtactgt ttgattgtac tgcacacagt gtggtttcaa 103980 aaatgtgtat ttgaattgga aaagagaaat atatgtcagg cactggggat acaatactga 104040 ccaaaggtat ataccctgaa tccaaaaata aatataatgt agttgctgta aacatattaa 104100 ttttaaaagat tgtcagaaga atatccatct tagttagacc tttgcaagat atatagataa 104160 gaaaatttct gaaagttaca taactaaaat agaaaccagt caaaatgaac ttcattctac 104220 cctggtttct tccctctaat gttcttatct gtcaatactg tgactgaaaa agccaaacct 104280 accaccacca ccaccactga caaaatccaa aaaactacag atatctacaa cattaattct 104340 aacaccaagt aacattataa cccacttaaa actgttcttt tttctttcttt tttttagtac 104400 agacagaact tttttttttt taatggtaag aaatatcatg atttcttat aaagaccttc 104460 tgtatgtaca aataaagcta tactatcata gtggataaat cagtaaacaa tatcttatgt 104520 aatctgtaat ttttcacaca agaaatttaa aaagtttttc aggttataga acagtatttc 104580 tggacacacc taacaaggca gtagctgaca ttctcaaact tcaaaacacc ctcactttca 104640 atacaaataa tgctgtgttg tacatttaac ctaaaactaa gagaaagcat tgttggttgg 104700 ccacaacttg aatttcttat tacaatgagg actgcttcag gattttacca ctaaactcag 104760 ccgttcagag aactaggaag atagtaacca tggtcactgt tcttcaaaag cactgatttc 104820 agatttgttg aagggatatt tcttagatct tcaagttttct gaaaaggttt ccttcattct 104880 ggttttctgg atttccttgt cattctgaag ttattcctct tgcacaggca aaattagagt 104940 actcattcaa taacaacaac aacaacaaca acaaagccat aaaatatgcc ttctttttttc 105000 tacacacca atttagctac tcagataca gaactaaat attagcaga aatcttgtag 105060 gtatgaagcc agttatgtat tcacattagt aagatgatt ccactgcatt catttaatca 105120 gcaaacattt acagaatgcc tactacatac cacaata ttagtgactg catattcatt 105180 taatcccgaa ctctgaaatc attattcctg gtttacaaa taggaacag gcttggatta 105240 aggttgcttg cccaagatt tatagtt aagattcact accaagtttg aaactcagat 105300 atgtctgagc caaatttct gctccttcca ctaagccaag ctgtctcca gcatggcttc 105360 cagcatactt agtatcttgc tgtatcaga gaaaacagg tacaggtgac agtgacgtga 105420 tgccattatg actatctctt tttataaa agacccttg ttgagataac tacaactc 105480 tctttctcag acctcctaca cattgcttttcttcaatca tcaggtcat gagccttctc 105540 ccctctccctc ccccgccgcc ccccacc CACTCCcc ctaacaagt aaagaaatc 105600 aaatgagatt tgattaagt gttttgtcta gactgcttca ggactaaagg gtcttggtaa 105660 tttgtaccag cacctcactt cttccccacg cccaaaaaact cacgtacaca gtttgattgt 105720 tcttgctttc taaagtgttc tcttttttt gagatggagt ttcgctcttg ttgcccatgc 105780 tggagtgcaa tgacccgatc tcggctcaac acaacctccg cctcccaggt tcaagtgatt 105840 ctcctgcctc ggcctcccaa gtagctggga ttataggcat gtgtcaccat gcccagctaa 105900 tttttgtatt tttagtagag acggagtttc tccatgttgg ttaggctggt ctcaaactcc 105960 ctacctcagg tgatccaccc gccttggcct cccaaagtgc tgggattaca ggcatgagcc 106020 cggccaaagt gttctgaaag ctatgtgtga atctgttaag tacaatctat acttacattt 106080 gattataaat attttgacga tctgaattgg taagatttta ggcaaaacaa caaaatcaaa 106140 tcccgtggac tctgacccaa agaatatatt cagctttgtt tgaatatatt tcatcttgct 106200 tccttaccaa ttctcaacac aactccagaa taactgttat taactcttat tgaatcttat 106260 tttgtactaa gccttgttaa atgttttacc tatgaattgt gatttcattg ttacagcaaa 106320 cctatgatat agatgctata taacagatga agaatgagg ttcagaacct gtgctacgct 106380 gcctcgcagg cacaatccat ctgataaag tagtcccttg aatctctt tctgaattcc 106440 agtcccagga cagtggaat accagtatt gtggtcaaag ataaaccatt cttggctcca 106500 ggtgagctaa tggttttaga taagaaa gatatttat tagaaaaatttgtaa 106560 agtataaaat tagactagga aaagctcccc ggttgaattt tatatta aaatccttta 106620 ctgaagttga aatctctcc tgaatttc tgcttgtat ggcctctg ttgcctcac 106680 aagtgaaatt taatcctaat gttaccttat tttccaagca taaccacc agtaggctgc 106740 tttgtcatga gtttagtag gtgtcagtag aaacgagacc agcagtcatt agggttacct 106800 aattcaaatc ttgactcatt ttgggtactt cctacaagat tagaatatt atcttccaaa 106860 ccaaaaacat acccaaggtt ccatgggaaa gggtgtagct tcaacttt ttaggtggca 106920 agaaaatcat tctcataacct ctcaaggtc aggaataggg tcgatggtcc ttaaaatttg 106980 gtctggggac cactggttgc tgaacctttt gcaggaggtc tgaaggtca gacctgtttt 107040 cacaatacat gttaagaagt taatggcttt ttgttgtca ttctttcca agtgtatttg 107100 attatacaac ttgggatt gttcctctga tagttaatgc atatactt atgttttaaa 107160 agtttgttag ttttgatttc tatacagta agtctcaca gatagaactc acatacaaa 107220 acactttgg gagtccttca taatttttaa gagtgtaag gaggttctaa gaccaaagg 107280 tgtggaact gctcttctag gtttcagaat tatgagcat aaagactc ttcatctgga 107340 agggtttaga gggtatttta tctaatcccc ttattttaca ggtttagaaa ctgattctag 107400 acatttaagt tcccagacta atgtcacaga agctaatgaa ttgcagaggt taattggaag 107460 cctggtctta acaccccag gttatcttta tgagttcatg aggatggcat atggataatg 107520 cacttcaaag ggtgttgtaa gtattaacta agttataca ggtcaaatgc atattagc 107580 actcaatgca cggccattga tcataaatg ctagtggttc tgatcagtga gatctaacc 107640 tctgcttaaa tacctttagt catcagcagc ttccactccc tgagtaacat gttgcatttc 107700 ttgatcaatt atatttttac agaattcttc ctttactgaa gttgaaatcg tctccttgaa 107760 atttctactt ggtatggcct ctctgtttgc tacacaaata aatttaatcc taattttatc 107820 tagcttattt tccaagcata accacaccaa tttcattaaa tgattcctca tgtggcatga 107880 ctttaaactc cgtcaccatc ctatttgttt ttctcaaaga gctccagttg actgctcctg 107940 tgaaattgtc catctattaa tgtaaatgtt ttttctaatt ttacagagct ccccgttgta 108000 ttgtgtacag tgttaaaata gttttctgag atttcttgac tctgttttcc caagtttctt 108060 gtggcccttc tctttccttc gtctctattc tgtgcggttt ttatttcact cccacagttt 108120 ctcattgctg tgaggccctg ttatggaatg agagccctgg ttttgaaagt tcacagaggc 108180 tagacttctc ttgtccctgt agtcctggct gagggcccac tacacttgtc tgttatccga 108240 gtgggcaaac gacctacccg ttttcatctg ctgggcggcc ggttatttgg ggggatcccc 108300 ctgttacagg tctgatctct gttgcttcct ttgggaggcc gaggcgggcg gatcaccagg 108360 tcaggagttt gagaccagcc tgaccaatat ggtgacactc ctgtctctac taaaaatgca 108420 aaaactagct gggcatggtg acgtgcgcct gtagtcccag ctactctgga ggctgaggca 108480 gaagaatcgc ttgaacccgg gaggcggagg ctacagtgag tcgagattgt gccactgcac 108540 tccagcctgg gcaacagagc gagactgttt aaaaaaaaa aaaaaaagtt tgtagccatt 108600 atctctggaa atattactc ttcctcattc ttctgcttat ctctttctgg aactccaact 108660 agatatatac tagacctttg attctattt tccacacctc ttaacctgtc tagcttattt 108720 agtcatacat ctctcaagct gcattcttcc ttggagcttt atctgtagga attctttgag 108780 ccttgattga gtttatattg cttcagagaa aactaaggtt tgcttcagct agttgcccag 108840 gaacattacc acctggttac cacttttaat taaggtcact gcttgaggat ttcagagcga 108900 cacagagccc tgtatgaggg cctgttatg gttataaatt cttggggtgt aggcaggggt 108960 ggggatcctg cttctttacc tggagctaaa actgagacag aaaaatccct gactgtccat ttttgtgtgg tgggtttatt ttctgttcac cctgaacaat gataggtgtt caccttgtag agctccccgc tttatgtggg ggtttcctat tagagaacta tcatatgtgg cctgttggct 109140 tattttcttg ccttcagcac ctgtgccagt acataagtta gaaacccag gtttccaggt ttcgaaaaac tctcagggca aaagttcgtt ttagcctatg cttagctccc agggtccttt gtacttggcc atatggattt cttttttttt ttttcttcat gtcaacactg tggttatatt 109320 tatctgtcta acctactctt ttattttg ttttatctgg tattttaatt gtttcatttg agaaagtttt tcatagtatc tgtttggtag ttggccattc tactaggagt ttaggagtta 109440 tacttaactc cttccaggga gatgttgga gatttttact aaaaatacaa tatttaaggt gggtattgaa gtactatcag aggggacctg gggtggagta tgaaaacaaa acaaaacctt 109560 acaaacggga father gttaggatat gtgagatgtt tggttttgct gggcttaaaa tagattgtg gggtatggaa ttgctgcaaa tgaggagat ggactcagag atgaggctca 109680 agagaggcca catgcaactt ttgagagtct tgtgtgtca cagtaggaa gatgaacttg 109740 tgaaatcacc aaagggtgga atatataagg aggaagctga cactgtcata tctatgcctt 109800 aggatgttta ttttggcagc agtgaaaaca aatcaggtag acagagtgg agcattgctc 109860 ttcaaattt agtcattgac tggcatcat gggagcttgt tagaatgca 109920 gatctcgggg tcctatttca gatttacca ctcagaatct gcattttaac aagactccta 109980 agtgtttcat atgcatagtc agttgatgtc tcaccagtg acctgcagag ccagtgatct 110040 gcaagcaag tgaacgttag ctttatttta aatttcaaga aagaagtctt aatttgccta 110100 gagtacatat cattgatgt tcacagtgtc actttatttg cctaataact agctgactct 110160 agatccttag cagcattaga tttagtattt gaggtttga ccctatgtac ctttgataag 110220 tagtgatttg taacttatga attaaatttg aattccttaa catgttgcta gttacaaac 110280 tctagtgtct ctagcagact attaagaaat tgagcaggtt tcgttctcca ttcactgtta 110340 acacatgcgg taactcacca ggcgcttaaa acaagtgggc tgtggtgcag ggtacttctt 110400 gtttagtgac agaatgaaa agatctaaga atatgatggt tttaataaa tatgataaga 110460 gatgaaga gttttaagta atagaactat tctaagttt ggatgtttgg tttagtgtct 110520 ctagctatat ttctgtttaa tgtcaaggca taatatattc gaaccatttt atttattaaa 110580 tttaataaac attgattgtc ctattagtca aagtttcaga aaaatgcaaa aagtcttgtt 110640 ctcaaaggaa tgctccctgg accatgcaca tcaaagtcgt gggtggctgc ttgtgggggt 110700 agaaaatatt aaaaatgcag aaactgggcc ctactgccga atcccaatgt acattttaaa 110760 ataagcagct tcctggccag gtacggtggc tttcacctgt aatcccagta ttttgggagg 110820 ctgaggcagg aggatcactt gaactcagga gttcaagcct gggcaacata gtgggacccc 110880 catctctgca aaaaatggaa aaaaagtaaa agcatctccc aaaggaattct gccagcagga 110940 aagttgtgtt ttcccccctc aaatctggaa accataattg ttcacttttt gaccttttac 111000 tggaatacag catactctga gaaaagtaac aacactcaaa taaaaaaata gaacattcta 111060 ttccagaacc tcctctagtg actccttcta gaaagcagtc tagcacccca cccctccaaa 111120 cacaaacata accaccatag tgacttttaa caccatagat tagtttttcc ttttttgaac 111180 tctttaaagt ggaataatac aatttatact ctgtctgttt tgtgttgttt ttgcttagca 111240 ttatgtctgt aaaatttgtc tatattgtta gctccagttt gtcattctca ttctcattgc 111300 tgtgtggttc tctgttgttt aaaagtacca gtggtaaaat tatcatttat gtggtttatc 111360 tctgatggac attagaggta tggtggtacc actgataggc accaaaatca agtttaataa 111420 ccactgttgt atattatttg ggaaaatgtg tactcttgac atgtttggca aatttttatt 111480 tctccaatct aaaatttaga aaattataat tttaaaatta tcaataaaaa tttacaaagt 111540 ttttactgtc aaatattatc taatagctca actagctcat gctagagtaa tacagccatg 111600 taatacagca ttaccactt ttctaagtgg tctatagcac tgaggaatta atagcaaat 111660 aagggaagca tttctcatg aaatcattc ttttaataa ttaaaaagaa atgagagtat 111720 tagatacca ccatttgcc accttcagtg tattaatgga tggaggcaat gatatcac 111780 agctgctaaa atcatagaa ggaaaccaga tgctagatga cacataatga agtacacat 111840 tattagacaa aggacaac caagttcaat aaagccctg gatccagctt ccaatttgcc 111900 aaaataag agaccagatg atatgctga attgcattat gtgtaataa tcagtcaaat 111960 ctacactacg aaagtcaga tcaacaata attttaagaa aaagaaaga atggaaata 112020 aacctgtaga ttaaaagaga ctgaatagaa gtagcaactc ttcttaaaaa tggtcaagat 112080 taaatatag ttatctaggg aggcttactt agctgataa gtgataata caggatgtaa 112140 ttagaata ttaaagaa gtgagttact taggaggagg gaaggggcta tgactgaatc 112200 agcacttgga ggagctctg ggctcgctgg caatgctg tgtggtggtc acagaatgt 112260 attctcttaa tatgctaagg tataaagtttt ttgtatagtt ttctgtatct gtattttatt 112320 ttactctaaa ggaagtagtt ttttaaaaaa gattatagat ttgctaatct aataaact 112380 cccctagac ttcatcagta atagtctagt gtcatctgga ttatcttcag caatcatttt 112440 cattctaaat tgtcatagtg tcatctcaaa gcagaaagag acagagagtt tgacaaagtg 112500 tcttaaaatg cctgatgtct gtcttaatga ttctaataga aactcttcag tacaatactc 112560 agacttactg cgcttacaac tacataatgg cttataaatt tgggaaactc aacagatttg 112620 ggaatacaac acatatcttg aagccagtta atttactttt tacatacctc ttcactattc 112680 cactaccagt gtgcaactgg taattcagtt gaattcataa agaattcact gagtttttct 112740 gaatttcttc tgatttcaag aggctagaag aactcagatt ataaagcatc aggttatcac 112800 ttttactata taggcacacc atggtttatt gcactttgct tctgattttt ttttaaaca 112860 aattgaaggg ttggagcaat cctgtgttga gcaagtctct tggtgccatt ttccagcagc 112920 tcactgtgtg tctctgtgtc ccattttgt aattctggca atatttcaat cttttcatt 112980 atttatatac ctattatggt tatctatgat cagcgatctc ttttatgtta ctatcataat 113040 tgtttgggga tgccatgaac cacaccata gagataaa agatggcaaa cttaataaat 113100 gttgtagta ttctgaccac tccaccacc agctgttccc atctcttt tctcaggcct 113160 ttttattccc tgagacaca cattgaatt ttgccaatta ataaccctac agtggcttct 113220 aagtgttcaa gtgaaaagaa gagttgcatg tctcattt taaatcaaa gctagaatg 113280 attagtgaag aaggcatgtt gaaagcagag acagggcaaa agctaggcct ttgtgccaa 113340 acatccaagt tgtgagtaca gaggaaagt tccttcttt tttcacttt ttcgtatgtt 113400 taaaaagtag agacagggtc tcgctatgtt gatcaggctg ttctgaact cctgacctca 113460 agcagtcctc ccacctacggc ttcctcaagt gctgggatta taagcatgag ccactacacc 113520 cagctgaaaa gttcttgaag gaaattaaa gtgctactct ggtgaacaca tgaattataa 113580 gcaaaacagc cttatgctg atatggagaa agttttagtg tctggataga agatcaaatc 113640 aaccataaca ttcccttaaa caaaagccta atccagagca aggcccgaac ttacttcaat 113700 tctatgaagg gtaagagggg aggaagcttc agaagaaaag ttggaagcta gcagtttggt 113760 tcctgaggtt taaggaaata agctgtctcg ataacatgta agtacaaggt aaagtagcaa 113820 gtgctgatgg agaagctgct gcagcatgtt atctagaatg tctagctaag atcactgatg 113880 aaggtggcta ccctaaaaga ttttcaatgt agatgaaaca gcactctatt ggaagatgcc 113940 atctaagact tttctagctg gataggggaa gtcagtacct ggcttcaaaa catcaaagga 114000 caggctgact ctcttgttag gggctaatgc tgctggtgac ctcaagtgga agccagtgct 114060 cattggtcat tccgaaaatc acagggtcct aagaattatg ctaaatctac tctgcccatg 114120 ctctgtaaat ggaacagagc ctggatgaca gcacagtttg ctagatatgt taagcccact 114180 cttgagtcct actgctctca gtgaaagatt cctttcaaaa tattactgct cactgacaat 114240 gcacctgta acccagaac tctgatggag atgtacaagg agatctct tttcatgc 114300 ttgataaca taataacatc tattgtgtag cccgtggatc aaggattcat ttctactttc 114360 aagttttatt atttaaaaaa tatattctt aaggctgtag ctgccgcagt gattcctgtg 114420 atgaatctgg gcaagtaaa ccaaaaacct tctgggagg attcaccatt ctaagtacca 114480 ttgagaacat tcgtgattta tgggagggg tcaaatatc agcattaata agagttggga 114540 agaaattgat tctaccccca tgggcaactt tgagggctc agactacag tgaggt 114600 cactgcagtt gtggtagaaa tagcagaga agtagagta gaacttgaca cagcgtgaca 114660 attgctgaaa tctcaagata aaatttgaat ggctgaggtg ttgcttttta ttgatgagca 114720 aagaaagctg tttcttgaga tggaactac tcctagtgaa gaggctttga aaattgttga 114780 atatcaca aaggacttag atattacat aaaattagtt gatacaattga taaagcagcg 114840 gtggtttggg aggattgcct ccaatcttga aagagatct acagttaggt aaatgctgt 114900 cacatagcct agtgtctttc atgaaaggaa gagtcaattg atgtggctaa cttattgtt 114960 gtcttatttt aagaaattgc cacagccata ctgattagtc agcagccatc aatatcaaga 115020 taagacccc caccggcaaa aaaattggac tcactgaagt ctcagttgat cattagcatt 115080 ttttaagca gtatagtcct tttaaattaa ggtatgtaca ttttttttac acataatgct 115140 attacacact tatagtagt gtaaatataa cttttattgc actgggaaac caaaacattt 115200 tttgtgacct gctgtattgc aatattacct ttattgcagt ggtctggaat tgaacctgca 115260 gttttctgag gtgtaagtat tggtgaaatc attaacctcc tcctctgtgt gtgtggtttc 115320 ttcaactcac aaaggatagc agccccagtg aaagtcgtta cagaaggcag ataaactcca 115380 ttttttttaa gactttgcca ctctgtgtgt gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt 115440 gtgtgtttac cttatcctag tgggccttac cacacatttc tattatgtga gatccaaaag 115500 tgatgtggta tacacaagag taattttcac cccattctta aaactgaaaa tgatgtttaa 115560 atcacttttt cttgggggaa aattcaaccc cgtggtaatt aagcttcact tttcctgaaa 115620 ttaatcttt tataaatttt ataaacttat aagaaatgta atacattttg cttaagtaac 115680 tagcataagc caaaatggca cttcattttt cttaggctca gcagatttaa tttaataaag 115740 attataatt gattttaatt aatgatgttt acgaaatgaa attaattga cagtgttgaa 115800 tagtaaagct gctaaaacca taagccaaag caatatgaat aaaagtataa tttagacaca 115860 atttaaacc agattttgaa aaactttact cggtgatatg gtcaggctca attgtatgcc 115920 tgctagttag attacttctt gtataggctg atatatgcat aaaattatta ttttgaatt 115980 ttaaataaaa ttatatttat ctctttaatg tgaatttacc tctttaatgt aaaaattata 116040 tttgtttttt gtccttgttt cttactgcac atatcaattc caggtcaagc atgagataag 116100 caaatcatgt taatttcatt ttcaactgaa ataagactat ttctgagctt attcttgttt 116160 gctgaataaa aaaagattgt tcatatgtgc gagaaattgc tgcagcataa tgttcactgt 116220 ttttctgtga gtagcaggat aatcttttct tcatagaaat ctacatcttg tctgggaaag 116280 attagtaaaa ctcatcttta atgtatgata aaactgcaga tctttttcct tttttctcaa 116340 gtcaaatttt cacagtcaga acattcagaa acaggatccc ttttccagtt ctacacttgt 116400 gttcaagtga aggaaaatct gttcagtttt ttttctgcag ctcctccagg tgatttccag 116460 taagacttga gacttgctga tatccttcct cactctcaag cccaaacagc aatagaaaca 116520 tttcaagatt ttcttttgta acatgttttt caaaagctca ttttcctttt acatccaaga 116580 atgttgtcct ttgaaataaa gaaaacccaa ccattttctt cacaccttac agagactgaa 116640 aaataagtac tacgtaggct agtttctaca gccattaatg tttaagtatt caacagactg 116700 tagcctactg ttttctttaa aggacccatt tcagttcaaa taccctattg agaagttttc 116760 cactgctaag tggattttgt gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt gtggtaaag 116820 ctgttcttta aatgagtgaa atgacctttg tttaatgaag ttaaccattt tataacatct 116880 ttcagatgtt aaaacatttt gccccaagag cttttgatat cagtactctt aacacagatg 116940 ttttttgtgt tagtttgggt cttctgagac acagatgtca agacaagatt tgatgcgcag 117000 ggaatctccc accccaccct actaccctcc tattgtcctt tggagcaatc cccattctag 117060 tacttctgcc ctgcttggta gcttgctggg agaagcccag aggcagcaag gccaggggtg 117120 gttgccatgg attccaaggt gcgatagatg gaggctgtca agcagttctg ttcctcatag 117180 caggttaggt tgaggggata tctgagtagg gtaccactgt ggccactgca ccctcctctt 117240 cagcctttga catctttccc tcatgtggac actctttact gtgttacgca cccacaggga 117300 tgttgtcact gtgttctgcc tttgacctac gggggcttct ttactatatg gattattcct 117360 catgcttctt agagtcaagc tttgccacct tgcccccttg ttggtctgcc tctgttcctc 117420 cccgccgcca tccctcacta cagaaaggct cttttcattc tgctttgact cccaaatttt 117480 ggactacctg cctgccacat acatacctaa cttgcttggc tccatctaat agctttttga 117540 ctaaattttt gaggaaaaga aggaagaaga gccatctggg tttcttacat ctgcaactag 117600 ctagaatatg attccattca ctgaataga gaaaataata ggaggctcta agaacaaatt 117660 tgggccttac gtatgtgtgc atgttgtggg gaaatagaag tttggatgtt aaaataatga 117720 atttggtgtg actttgggac accttcttga attaatagg ctcagtagag gagtctgact 117780 ggagataata gtatggggag tcattagctt ctgtgtgata gttggaaccc tgactttcaa 117840 cgaaacaaca aaggagggag gagctagcga tggagcacag taacagtgct gcctgaggga 117900 tgcactgagg aatgtaccaa ggaaaattaa gggacaggag agagttgtaa agagagctag 117960 tgaccaacag aataaaga tacaaaaatg gcaaaagagt ctttgagatt taacaaccag 118020 tttaaaattt agttattatg gagtaagccc atatcacaca ggtggtggcg tatcacacag 118080 ggattaaatt tagccaaaac aaaatatgta ttataattca aataacaaaa aatatatatt 118140 gtcatgtgga ctgaggaata gtcttttgca tcctttccag taaagatata tatgattgac 118200 tagtgaagtc tatttaaatt attcagtgta catccataaa actttatcaa ttactttctg 118260 tgtatatgat gacacttgcc agtattgccc attttgtgct gattttgtta gtctacatta 118320 ctaaggagct tttcatcaaa ttttgcagtc cctgaaagat tttcatcttt aaagttacaa 118380 atgtgatttc tcagctgcag tatagaatat atggaaccag aaatactcaa aaaaataattg 118440 ttttcgaagt attaatcttt ttagtcacag ttgtttttt acatcctgtg ctgaaaataa 118500 caagaaattt gatacagagg gaaaaatgat ttattatgac ttagtagaca atttacaaat 118560 gtgtgttaag atattaggat atatgtccta ccagtttcaa aagtactaca agtgacttgt 118620 tcaatacaga gtacaacttt aaaaaatgta tttaaagtaa ttgacgttgt gtttgtgacc 118680 tggctcgaag ttcttttttg gtgaagagca tgcttagtac atgattgtct ttaaaaaagat 118740 ctgataatta tttactcagt aaatgttttg agtgccttat gagtcaggca tttttgtggg 118800 tgctggagat aatagtgatg aaaaacaaaa gtcccttttc cttatagaac ttaaattcta 118860 gtgtgggaag gcagatagta cagaataaa ttgatggatg gatgatgga taggtaggta 118920 tttgctatat agcaggtact atttttgctt ttatatagtg ctgtggaaat gagtaaagtc 118980 aggacaagg aaagagaag gtgatgctgg ggggtattat tttaagttgg atggttagggg 119040 aaagtatcat tgaatagggg acatttgaac agagtccctct atgaggaag tgaaagaat 119100 aaaaagagga atagctagca caagactct gaggttgcag cacacttac ccctcaagaa 119160 agaacggtga cagaaagggt ggaacaagt gagagagtag taaatatga gttcacagtg 119220 gtggggatgt atgtagatga tagaggacc siacaggcaa ccaaaaga cattggcttt 119280 tactctgagt gaatgggaa gctcttagtg ggtgttgagc agtggagta taagataaaa 119340 cttattcat catgcattc aggtacttac tcctaatcat agtattaat aattattaa 119400 tttggggtat agaaagttca tatatgaagt ggaggtgtt ggctcttta agaattcagt 119460 gaaaatccta aacttcttgc agaaagtgat tccaagcttt gagttattct tcctgatgat 119520 cagtacagtt ggtttacttt cttgttatct ttgtcctaaa gcttcttaaa tcactttgta gctcaagcct aatggattat acctgcccat gtaaattctg aaaatgttaa tgttgcctag tgattcagag gctttagtaa tttacttaaa ctacttcttg ttttattggt ataaactgta ttcctcagtg tctactatga tttcaaagtt agtatttgcc ttggaatttt tctttgaagc tggcaactct agttcaatat aagacaggct ctcagagctc cacttatt acaactgtat ctatgcccac ttttattcct ctaagcattc ctagataag catttcaaat ggttttgaat tatcaaaggt ctttttgaaa aacaaggtta ttgagaaaat gtttaaaaag ttcatgagaa agttgtctaa aatacacccc cctcccccaa ggtaggcctg aaatgccact aaatcaacaa aggatagtca ctaaagtta ccctgtattt tctaggactt ggggaagtc atggagtagc tgtgctttct ctaagtaacc tattttaaat ttttttgaag agcaaatta ttatacctct ttttcatcca gaatggagct gactgtaggc atctttttaa agtacccata ggtcaggacc tctctggact ttccactacc ttgaaagaca ctgccagaag aatgttgttc cccacactta 120240 aaaaaggaaa agtaatgttc ttttctccag ccattatttt atgcaaagtc caactttatt 120300 ttatctgagc tatctgaact ttcaatttat ttgaaacatt tattgattaa tatctataat 120360 ggagctttta atttctctga tcatttatcc tttgttaggt tagcagaact gtaacaacac 120420 agtcactttc acagccacga atgatacttt tatagtcatt tgtggacata tactgtgcag 120480 agtatcacaa agtttgagcc acctgacaaa cttatttcca gttgagatct gcagggtgat 120540 gctctgcctt cttgttgcag ctctcatacc atgaacaagt gtcattttca tggtccatga 120600 ggaaaaagca ttttcctcat tttggtgctt tttgttagtg attgtgcagt ttagaatggc 120660 ccccaaacat agcctgaagt tctgtttaat gttccgaagt gcaggaaggc tgtaatttgc 120720 cttaaagata aactaatgtg tgttaaagaa acttaattca ggcattagtt ataatgctgt 120780 tgaccatgag ttcgatgcta atgaatcaat gtatattaaa gatatattta ggcagaaaca 120840 cgcataaaaa aggttatgca ttgatcagtt ggcaacagtg tgtgaccag aggcttgtga 120900 gaactgtatt tcccctagga gcaatggctc agtatttgtt aattcagtgg ttgcagcaat 120960 tttatagaac aciattactg tgaatggga tcactgtat ttgattaacg gtggtgattt 121020 atagggactt tagataccag aaatgtttca taattccctt tctctgaat cactgtttta 121080 atgttta atgcatgcat gcagagttgt gatgttaaac atattttac tgtggttct 121140 gtcaaaaa gatgaatgt cattggttaa cttgaaagg acattattct aacattatc 121200 ctccagaaaa ttgacatgta caggaagcat attgaatgct cagcaaataa ttgttttag 121260 agtaataatc tttgagtatt gtagtgattc gagttttgga aaagaaggca gtatcagtgt 121320 Tagagataa tattctttca ggattttg tagttacttt aaggtgcatg aaggagact 121380 cagttgggtg ttaatctt gtccctgctt tacttgaac tagtaatctt gagaaattta 121440 ctaaatcatt ttgagccttg attaccttgc ctgcaaagtg aggaacattt tcaatttaaa 121500 attctatttc ttttagt attctctcctg accttgaatc atttctattc ccatcatgtc 121560 cagttgccaa gaaaaccatg caacttaatg ttgtttgtta gccatcagat tttatttac 121620 tgaactcaag ttcagtcaca tcagttaccg aaaataat aagttctata ttaatattg 121680 atatatcttg acatttgta ttatgtag aagaaataa agaccttcct caattttg 121740 gatatgggct tctgtttgtt gatgtttgtg ttttatgata cactgttgta aatcatacta 121800 aaggttttct ctgaaaaaga ctagaattga caatacttca ttgttagca gtttcaagtt 121860 ttagatcacg gtgcataat ttctgtgtg tgcacacat gttggcattt tatctgactt 121920 aaatgtc catatagata ccaggaagg aaaatgta agaatgaata tcatgaaag 121980 atgctgtatc agataaaatt ctagagccta ggttaaaaaa cataaaggca aacatgcttg 122040 atatataaaa attgagaaat atgataaaa gaagtaagtt taagcatca gtataccac 122100 tgcctaagat gcagtttatt ttgaaatgtt gtctcttagt ctcatacag tttaaaaatc 122160 atactataat cacaatttcc agcattttcc ccttagcata atatatta acatccatgt 122220 ttttaaaaat attttatgaa cgtcatgttt agggattaca ccatatatat cccatctcat 122280 agattccttt atattgaca tttggatttt tattttacatt ttttattaca tttttttta 122340 tctttatttt tgcttcgt ggataactg cagtgagcat cctctgtata aatttttt 122400 ttctgtttta ggattacttc cttaggatag attgccagaa gtggagttac tggtcagag 122460 ggtatgaact tatgaacttt ttttaaat aaatttttg ttcattctct gtccagtcat 122520 ttgtaaaaaa attaaaata taatgatt attgttacc tgctagaaaa ctgtgtctga 122580 agcaagatt ctgtgatcag aaagttttgg gaataccca gggtaaaag ccttttaatc 122640 tgatttacct cagcattcc caatttact gaacactgaa aatttttt gatacactc 122700 ttaaaatttt gtggaagttt tatatagat atagtctatg actactgat gtaaaattaa 122760 aattgtttta ttgcttgaa atattatgtt ttattggtca aaggaattaa actataaatc 122820 ttcatgctaa aaattattaa aagggattag tgttgtttac tatggttttt gtgcatgtct 122880 ttataaagtc ttataacttt taaaattgaa atgttctata ttgtttacta aagaacattt 122940 taatgccttg gtggcatcaa tacttttttg caatcattaa tgatatttag aaagtagaca 123000 tataacatga aagtagaaca taatatagat tgtacaaatc ttgtttttta ccctattttc 123060 ccctgcag 123068 <210> 5 <211> 23 <212> RNA <213> Homo sapiens <400> 5 uuauugcuua agaauacgcg uag 2:3 <210> 6 <211> 102 <212> RNA <213> Homo sapiens <400> 6 gguccucuga cucucuucgg ugacggguau ucuugggugg auaauacgga uuacguuguu 60[[ID=:33]] auugcuuaag aauacgcgua gucgaggaga guaccagcgg ca 102 <210> 7 <,211,> 2469 <212> DNA <213> Homo sapiens <400> 7 agatggtgta gatcagatcg atttgattgc attagatgat tttttccctt ccccactcct 60 It should be noted that there may be some inaccuracies in the translation due to the complexity and potential ambiguity of the original text, especially in the case of some tags and sequences. It is recommended to double-check with relevant biological or technical experts for more accurate interpretation.ttctggaagc tcgcatcagc tgaggact cgcctgggac tcctcggaag catgagcaag 120 ccgccaccac gcgaaggcac tggggcacag ccagcgcgag gcgccgaggt cccttcccaa 180 ggcttgttaa cactgtacc cggcactcgg aggagaag cagctcacac tgcccagagc 240 ctacctcact gcacatcaga tgactccctg gctctacac acagttggag ttccgcttga 300 aacctggatt tagaggtt ctctggccgc catggcactc aatcatacca cctagagtgg 360 actggccgag accagactgg gtaccaagca gagaagtgca gaggaaagca ctgggagagc 420 accagaattg gaaatagagc ggccattgg atttgggcag gaagcagccg agcacagctt 480 tggatccttc tttagggaa tcgagttatg gatttatggt cccggtcaag ctcagcccat 540 ccccaggcag gggcggggctc agcgagcagc agagttctg gtggcggcgg cggcggcagt 600 agcagcggca gcggtagcag cggcagcggt agcagcggca gcggcagctt ggtcctctga 660 ctctcttcgg tgacggtat tcttggttgg ataatacgga ttacgttgtt attgcttaag 720 atacgcgta gtcgaggaga gtaccagcgg caggggggca gcggccgccc tcccagcccc 780 accagctggc cactaaacgc ccgtggttgc caaggcatcc aaagcctctg ggatgtgttc 840 tgactgtaaa aactctgatg ttgtgaaaaa agcttacgct ttgcctccac tcaaaccaga 900 tggtgtttcg ctcttattgc ccaggctgga gtgcaatgac gtgatcttga ctcaccacag 960 cctctgcatc caggattcaa gctattcccc tgcctcagcc tcccaaaatg ctgggattat 1020 aggcgtgagc caccacgcct ggccagcatt cccaattttt aaaaatgaat gattggcaca 1080 aatcttagaa agccattttc tgtagatttg aaagcaatgc tatttacatt gttactactt 1140 tcttgttaaa tcttgcatgt ctgcagtatg tgttgtaata gaaacctaag attatgatct 1200 gctgtattca tatttgaaga agaaaatttc agactgtata atcaactagt tgatgattca 1260 tatttgcttg tacaaagtta aaagtgtaac ttgccagaaa agaaggaagc ctgaaaagta 1320 ttctaaatac attaataaga agggttctac atgaattaat ttttgttttg ccatctacag 1380 agttcctgcc acattctagg cacttcatat ttgctgcaac atttattcag acattgacag 1440 aacaagagaa acgaagttaa attttaagta ccatggattg aaattaaatt tagggaagat 1500 attttatagt atgaattgtt catctgtatt taacaaggta ttcatttatt ttgggcgatt 1560 taaggaaggt cctttctgga aacaggatta caaacatatg gacctattta gtcaatttca 1620 accttgtgat tttgaatctg acaggttctc agctgctttt attaaataac ggattttctt 1680 aataattact gtactcaaac ttagcaaaaa gctctattta tagcccagtt ttttagtcac 1740 acactattgt gtcttgtcaa attgaaacca tatactacat tctttactta ttaagatggt 1800 ctttctttgt aataattttg gagtaaatag tttacttatc taaacctctg atttctgatt 1860 taacagattt ttgaagcatt tattttcctt accatacata aaaattgtca gttgaggaca 1920 aggaaggatt aacctggact acggtgaata attgttcagg ttgcttactg tgtaactcca 1980 gaggagcatt cacatggtac aatttgcaga tttaagtatt tattacaacc atttctggc 2040 agataacagt ggaacaccct gttctgttaa aattagttta tttgacaaa ttgcctacag 2100 atggacataa actgtcttga ggaagggcac ctgctttgga ctgaatcgtg tccccccaaa 2160 atcaaatgtt gaagcctaat ctctaatatg atggtatttg gagatggggc ctttgggaga 2220 taactaggtt tagatgaggt caagagtgtg gggccttcct gattagtacc ctgaaaagag 2280 aaaacaccag agagcttgcc ctctctccct cttaccccac aggcacacaa agaggtcatg 2340 tgagtacaca gtgagataac aaccacctat gagaaaacag aagaggcttc agagtgaaat 2400 ctactttgct ggtactgtaa tcttggacat tattctctag aactgtgaga taataaattt 2460 atcttattt 2469 <210> 8 <211> 21 <212> RNA <213> Homo sapiens <400> 8 agaccuggcc cagaccucag c 21 <210> 9 <211> 75 <212> RNA <213> Homo sapiens <400> 9 guggggagcc ugguuagacc uggcccagac cucagcuaca caagcugaug gacugaguca 60 ggggccacac ucucc 75 <210> 10 <211> 1037 <212> DNA <213> Homo sapiens <400> 10 ctgtgggaca gaggaacagg cagagatcag agggcaggct caggttggga ggagtgggga 60 gcctggttag acctggccca gacctcagct acacaagctg atggactgag tcaggggcca 120 cactctccct cctctggtga tgtgacctca gctggtttct tcccactcgg cctggttt 180 cccatcctgg agtgggatta agaatccttg tcctggccct gtgcagtggc cacacctgta 240 atcccgacac tttgggaagc ttagatggga gaatccctag gggccaggag ttcaatacca gcctgggca catagggaga ccctgtctct acaaaaaaaa tttttaaca ttagcccggt gtggtggtgt gagcctgtag tcctagctac ttagaggcag atgtgggagg atcacttgag 420 cccagtttga ggctagtcca ggcaacatgg caagatccta tctctacca aaatatatat aaacgtgcgt gtgtgtgtgt gtgtgtgtgt gtgtataaat fatheraaaga atccttgtcc 540 tgcctgtctc atgggcagct tggaggaac actgtttttt tgtttttttt ttttttgaga tggagttttg ctcttgttgc ccaggctgga gtgcaatggc acgatctcag ctcaactgca 660 acctccacct cctgggttta agcgattttc ctgcctcatc ctcccgagta gctgagatta 720 caggtgccca ccaccacacc tggctaattt tttgcatttt tagged ggggtttcac 780 catgttggcc aggatggtct cgaactcctg acctcaggtg agccacccca ctcggcctcc 840 cgaagtgctg ggattacagg catgagccac tgcgcccagc ctggaaacac tattgacaag 900 tgaggaggcc tagtccattg agtatcagct agggctacaa acttccaaat cggtgaatca 960 ggtccagaga gggacaagtg ccccagggtt acacaatcat ttgctgaagc agaggttgct 1020 gccatctttg gcctcac 1037 <210> 11 <211> 23 <212> RNA <213> Homo sapiens <400> 11 ggcagguucu cacccucucu agg 23 <210> 12 <211> 98 <212> RNA <213> Homo sapiens <400> 12 guguaguaga gcuaggagga gaggguccug gagaagcgug gaccgguccg gguggguucc 60 ggcagguucu cacccucucu aggccccauu cuccucug 98 <210> 13 <211> 1412 <212> DNA <213> Homo sapiens <400> 13<00030�4>gtgagggcgg gcgcgggcca gcggccggga agccctaggc caggcccctc ccctgaagga 60 agggcatagg gcgggtcctg cctcaggggg cttgcgagga ccggccaggt tcatctcatg 120 cagcatcaga caaccactat gcagagggat tttatgacgt ttttgaaaaa ttgggaagac 180 aatggtttga caccacttt gcaggtttag acgaagagat gcgtactgtc aagctggcct 240 gttctctgtc cccgaggcag tcagccagca ccctgcagcc ccgcgccaac cccacactct 300 gctaagccct cgctttgggg cttgagggag acagaccctg cttggaagga ccctggaggg 360 agggttctgt cctgcttggg ccaggatgcc cagcccctgg ggaccccggg gggacatgct 420 ggaagaagtg gcgaaggaca cgtggccccg tcagccccag acgccgcacg gctgtccctct 480 ccaacaatat cctggtgctg agtgatgact caggcgactc cagcatcagt gattttgttg 540 aagagggcag ctgccagcct cccgacctgc ctgccgggcc ccagctgccc tgcccccaac 600 cccaacccac cccactccac cccctaggcc caggacacat ggccctgtag cgatcccctg 660 gcacgcagac atgggtttta tgtgggggagg gacaggctgg gttggcctct gtccccaccc 720 tgagtcctga gcacagaagt aatacggcag ctgtggtaat atctacccag taccctgtgc 780 ctcctcacac ccacgtgacc agccaggcag ggttcaaagc cagcagccaa ggcaggctgg 840 gttggaggta gtgccaggcg taacctgcat tctttccaga ccctacccaa ccctggggcc 900 agtggtggct caagtgagag tgagctccag ctctgagtgg gcatggcagg gctggaccct 960 aaaactggac tccggcagcc ggcaggaccc ctgggacact ccaggcctca gtttccccat 1020 caattcccac ctcctgggga gccgagagtg atagtgtagt agagctagga ggagagggtc 1080 ctggagaagc gtggaccggt ccgggtgggt tccggcaggt tctcaccctc tctaggcccc 1140 attctcctct gcactgtaac atttgaggcc cacgcacaca gtccctcccc aggtctcagg 1200 gttgggcaca gagtagggcc ctgggcaggg atggggggtg gcagtgtctc caacgcccct 1260 tccagcctgg actgtgagcc atccaagtgt tggcaaagga ccctgtgctg gatgcccccg 1320 cccggcacac cccactgacc ctccccctgc ccccacccgg cacaccctgc tcaccctgct 1380 caccctgccc ctgcccctgc ccctgcctgc ag 1412 <210> 14​​​​​​​​​​​​​​​​​<210> 15 <211> 8 <212> PRT <213> Artificial sequence <220> <223> synthetic peptides <400> 15 Gly Gly Gly Gly Gly Gly Asp Asp 1 5 <210> 16 <211> 10 <212> PRT <213> Artificial sequence <220> <223> synthetic peptides <400> 16 Gly Gly Gly Gly Gly Gly Gly Gly Asp Asp 1 5 10 <210> 17 <211> 12 <212> PRT <213> Artificial sequence <220> <223> synthetic peptides <400> 17 Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Asp Asp 1 5 10 <210> 18 <211> 7 <212> PRT <213> Artificial sequence <220> <223> synthetic peptides <400> 18 Ala Ala Ala Ala Ala Ala Asp 1 5 <210> 19 <211> 8 <212> PRT <213> Artificial sequence <220> <223> synthetic peptides <400> 19 Ala Ala Ala Ala Ala Ala Asp Asp 1 5 <210> 20 <211> 7 <212> PRT <213> Artificial sequence <220> <223> synthetic peptides <400> 20 Ala Ala Ala Ala Ala Ala Lys 1 5 <210> twenty one <211> 8 <212> PRT <213> Artificial sequence <220> <223> synthetic peptides <400> twenty one Ala Ala Ala Ala Ala Ala Lys Lys 1 5 <210> twenty two <211> 7 <212> PRT <213> Artificial sequence <220> <223> synthetic peptides <400> twenty two Val Val Val Val Val Val Asp 1 5 <210> twenty three <211> 8 <212> PRT <213> Artificial sequence <220> <223> synthetic peptides <400> twenty three Val Val Val Val Val Val Asp Asp 1 5 <210> twenty four <211> 7 <212> PRT <213> Artificial sequence <220> <223> synthetic peptides <400> twenty four Val Val Val Val Val Val Lys 1 5 <210> 25 <211> 8 <212> PRT <213> Artificial sequence <220> <223> synthetic peptides <400> 25 Val Val Val Val Val Val Lys Lys 1 5 <210> 26 <211> 7 <212> PRT <213> Artificial sequence <220> <223> synthetic peptides <400> 26 Leu Leu Leu Leu Leu Leu Asp 1 5 <210> 27 <211> 8 <212> PRT <213> Artificial sequence <220> <223> synthetic peptides <400> 27 Leu Leu Leu Leu Leu Leu Asp Asp 1 5 <210> 28 <211> 7 <212> PRT <213> Artificial sequence <220> <223> synthetic peptides <400> 28 Leu Leu Leu Leu Leu Leu Lys 1 5 <210> 29 <211> 8 <212> PRT <213> Artificial sequence <220> <223> synthetic peptides <400> 29 Leu Leu Leu Leu Leu Leu Lys Lys 1 5 <210> 30 <211> 19 <212> RNA <213> Artificial sequence <220> <223> synthetic RNA <400> 30 uucuccgaac gugucacgu 19 <210> 31 <211> 19 <212> RNA <213> Artificial sequence <220> <223> synthetic RNA <400> 31 acgucacacg uucggagaa 19 <210> 32 <211> twenty two <212> RNA <213> Artificial sequence <220> <223> synthetic RNA <400> 32 uaccugaauu cccaaaagcu uu 22

Claims

1. Use of RNA that functions as a mature miRNA in the manufacture of a pharmaceutical composition for treating solid cancers, The RNA is: A mature miRNA consisting of the sequence represented by SEQ ID NO: 2; The solid cancer is colorectal cancer, pancreatic cancer, tongue cancer, mesothelioma, uterine sarcoma, osteosarcoma, breast cancer, or lung cancer.

2. The use according to claim 1, characterized in that The RNA is used in the form of double-stranded RNA combined with a complementary strand.

3. The use according to claim 2, characterized in that The double-stranded RNA is a double-stranded RNA containing a portion of mismatch.

4. The use according to claim 1, characterized in that The RNA is chemically modified.

5. The use according to claim 4, characterized in that The chemical modification is one or more chemical modifications selected from LNAization, BNAization, ENAization, 2'-OMe modification, phosphorothioation, S-TuDization, morpholino modification, peptide addition, sugar chain addition, aptamer addition, hydrophobic molecule addition, polymer addition and non-modified DNA addition.

6. The use according to claim 1, characterized in that The pharmaceutical composition further contains a nucleic acid transfection agent.

7. The use according to claim 6, characterized in that The transfection agent is a lipid-based transfection agent, a polymer-based transfection agent, a magnetic particle-based transfection agent, an exosome for nucleic acid delivery, or a viral protein for nucleic acid delivery.

8. The use according to claim 6, characterized in that The transfection agent is a transfection agent containing a peptide represented by the amino acid sequence of GGGGDD (G4D2), GGGGGGGDD (G6D2), GGGGGGGGGDD (G8D2), GGGGGGGGGGGDD (G10D2), AAAAAAD (A6D), AAAAAADD (A6D2), AAAAAAK (A6K), AAAAAAKK (A6K2), VVVVVVD (V6D), VVVVVVDD (V6D2), VVVVVVK (V6K), VVVVVVKK (V6K2), LLLLLLD (L6D), LLLLLLDD (L6D2), LLLLLLK (L6K) or LLLLLLKK (L6K2).

9. The use according to claim 1, characterized in that The pharmaceutical composition is for topical administration.

10. The use according to claim 1, characterized in that Used in combination with other anticancer agents.

11. The use according to claim 10, characterized in that The other anticancer agents are one or more anticancer agents selected from metabolic antagonists, anticancer antibiotics, molecular targeted drugs, hormone preparations, immunomodulators, and plant-derived anticancer agents.

12. The use according to claim 10, characterized in that The other anticancer agents are one or more anticancer agents selected from interferon, interleukin, topoisomerase inhibitor, microtubule inhibitor, alkylating agent and platinum preparation.

13. The use according to claim 10, characterized in that The other anticancer agent is a BRM preparation.

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