Untitled record

Full description, sister’s background

The present invention relates to microorganisms capable of positively modifying inflammatory disorders and can be used in therapeutic or preventive medicine.

Bacteroides thetaiotaomicron has effective anti-inflammatory effects

<p dir="rtl">5 In vitro and in the living cell in vivo:</p>

(Kelly et al. Commensal anaerobic gut bacteria attenuate inflammation

by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA.

(104-12:(1)5;Nat Immunol. 2004 Jan. It modulates the molecular signaling pathways of the factor

(Kelly et al, Commensal anaerobic gut bacteria NF-κB atte nuate inflammation by regulating nuclear-cytoplasmic shuttling of 10

On the face of PPAR-gamma and RelA. Nat Immunol. 2004 Jan;5(1):104-12)

Specifically, it stops the binding of the active component of nuclear factor kappa B (RelA) to the main genes in the nucleus, thus preventing the activation of pro-inflammatory pathways.

<p dir="rtl">15 (2004 Kelly et al, Supra). The complete genome sequence of the bacterium has been determined</p>

Bacteroides thetaiotaomicron and its appendix by Gordon's group

[Xu et al, 2003 (Washington University School of Medicine, USA)

A genomic view of the human-Bacteroides thetaiotaomicron symbiosis.

.Science. 2003 Mar 28;299(5615):2074-6]

20 General description of the invention

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The current invention is based on the discovery of a strain of Bacteroides thetaiotaomicron that has amazing anti-inflammatory activity against inflammatory disorders. Accordingly, Bacteroidetes strain is useful as a therapeutic or preventive medicine against inflammatory disorder and/or autoimmune disorder and/or allergic disorder.

According to a first aspect of the invention, there is a Bacteroidetes bacterium deposited under NCIMB registration number 42341 (with the National Collections of Industrial, Food, and Marine Bacteria), or a derivative thereof.

According to a second aspect of the invention, there is a dietary supplement comprising Bacteroidetes as defined in claim 1 and a nutritionally acceptable excipient, carrier or diluent thereof.

<p dir="rtl">10 According to a third aspect of the invention, there is a feed, food product, diet supplement or food additive</p>

It includes Bacteroidetes as defined in Protection No. 1.

According to a fourth aspect of the invention, a Bacteroides bacterium as defined in Claim No. 1, a composition as defined in Claim No. 2 or 3, a pharmaceutical composition as defined in Claim No. 4 or 5, or a food supplement as defined in Claim No. Protecting ingredient 6 15 or 7 or feed, food product, diet supplement or food additive as defined in

Protective element 8 or 9 for use in modifying inflammation of a tissue or organ in a subject.

According to a fifth aspect of the invention, Bacteroidetes as defined in Claim No. 1, or a composition as defined in Claim No. 2 or 3, or a pharmaceutical composition as defined in Claim No. 4 or 5, or a food supplement as defined in Claim No. Protecting ingredient 6 20 or 7 or feed, food product, diet supplement or food additive as defined in

Protection element 8 or 9 for use in the treatment and/or prevention of seizure disorder; Where the aforementioned arthritis is an inflammatory arthritis and/or autoimmune arthritis.

According to a sixth aspect of the invention, Bacteroidetes as defined in Claim No. 1, a composition as defined in Claim No. 2 or 3, or a pharmaceutical composition as defined in Claim No. 2 or 3.

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Identified in claims 4 or 5, a food supplement as defined in claims 6 or 7, a feed, food product, diet supplement or food additive as defined in claims 8 or 9 for use in reducing rupture of a colon, preferably The aforementioned subject suffers from inflammatory bowel disorder.

<p dir="rtl">5 According to a seventh aspect of the invention, Bacteroidetes as defined in claim No. 1, or</p>

A composition as defined in claims 2 or 3, a pharmaceutical composition as defined in claims 4 or 5, a food supplement as defined in claims 6 or 7, a feed, a food product, a diet supplement or a food additive As defined in protective element 8 or 9 for use in reducing the expression of one or more activated genes

<p dir="rtl">10 For inflammation in a cell or cells in a subject.</p>

According to an eighth aspect of the invention, Bacteroidetes as defined in Claim No. 1, or a composition as defined in Claim No. 2 or 3, or a pharmaceutical composition as defined in Claim No. 4 or 5, or a food supplement as defined in Claim No. Protection ingredient 6 or 7, feed, food product, diet supplement or food additive as defined in

<p dir="rtl">15 Protection element 8 or 9 for use in increasing the proportion of regulatory T cells (Tregs) in the alimentary canal or section of the alimentary canal.</p>

.the alimentary canal

20

According to a ninth aspect of the invention, a process for producing a pharmaceutical composition in accordance with claim 4 or 5, said process comprising mixing said Bacteroides bacterium with an excipient, carrier, or pharmaceutically acceptable diluent, wherein said Bacteroides bacterium is optionally preserved in said process.

According to a tenth aspect of the invention, a method for modifying inflammation of a tissue or organ in a subject wherein said method includes administering to the subject a Bacteroidetes bacterium as defined in claim No. 1, a composition as defined in claim No. 2 or 3, or a pharmaceutical composition as defined in claim No. 1

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Identified in claims 4 or 5, or a food supplement as defined in claims 6 or 7, or a feed, food product, diet supplement or food additive as defined in claims 8 or 9.

According to an eleventh aspect of the invention, a method for treating and/or preventing inflammatory arthritis

Autoimmune disorder and/or inflammatory disorder 5

In a subject where the said method includes giving the subject a Bacteroidetes as defined in Protection No. 1, or a composition as defined in Protection No. 2 or 3, or a pharmaceutical composition as defined in Protection No. 4 or 5, or a nutritional supplement as As defined in claims 6 or 7, or a feed, food product, diet supplement or food additive 10, as defined in claims 8 or 9.

According to a twelfth aspect of the invention, a method for reducing colonic rupture in a subject wherein said method includes administering to the subject a Bacteroidetes as defined in claim No. 1, a composition as defined in claim No. 2 or 3, or a pharmaceutical composition as defined in claim No. 1 in protection element 4 or 5, or a food supplement as defined in protection element 6 15 or 7 or a feed, food product, diet supplement or food additive as defined in protection element 4 or 5.

Guard element 8 or 9, preferably where the submissive is suffering from inflammatory bowel syndrome.

According to a thirteenth aspect of the invention, a method for reducing the expression of one or more proinflammatory genes in a cell or cells in a subject, where said method includes administering to the subject a Bacteroidetes bacterium as defined in claim 1, or a composition as defined in 20 claims. Protection No. 2 or 3, or a pharmaceutical composition as defined in Protection No. 4 or 5,

or a food supplement as defined in Protections 6 or 7 or a feed, food product, diet supplement or food additive as defined in Protections 8 or 9.

According to element fourteen of the invention, a method for increasing the proportion of regulatory T cells (Tregs) in the gastrointestinal tract or a section of the gastrointestinal tract wherein said method includes administering to the subject

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or A feed, food product, diet supplement or food additive as defined in Protection 8 or 9.

<p dir="rtl">5 According to a fifteenth aspect of the invention, Bacteroidetes as defined in Claim No. 1, a composition as defined in Claim No. 2 or 3, a pharmaceutical composition as defined in Claim No. 4 or 5, or a food supplement as defined in Claim No. 2 or 3. In claims 6 or 7, a feed, food product, diet supplement or food additive as defined in claims 8 or 9, for the manufacture of a drug to modify inflammation of a tissue or organ in a subject.</p>

<p dir="rtl">10 According to a sixteenth aspect of the invention, Bacteroidetes as defined in claim No. 1,</p>

a composition as defined in claims 2 or 3, a pharmaceutical composition as defined in claims 4 or 5, a food supplement as defined in claims 6 or 7, a feed, a food product, a diet supplement or a food additive As defined in claim 8 or 9 for the manufacture of a drug for the treatment and/or prevention of inflammatory arthritis and/or arthritis.

<p dir="rtl">15 Caused by autoimmunity in a subject.</p>

According to a seventeenth aspect of the invention, Bacteroidetes as defined in Claim No. 1, or a composition as defined in Claim No. 2 or 3, or a pharmaceutical composition as defined in Claim No. 4 or 5, or a food supplement as defined in Claim No. 1 In claims 6 or 7, a feed, food product, diet supplement, or food additive as defined in 20 claims 8 or 9 for the manufacture of a drug to reduce colon rupture in a subject, preferably where the subject suffers from inflammatory bowel disorder.

According to the eighteenth aspect of the invention, a Bacteroidetes as defined in Claim No. 1, a composition as defined in Claim No. 2 or 3, a pharmaceutical composition as defined in Claim No. 4 or 5, or a food supplement as defined in Claim No. 1 In protection element 6

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or 7 or a feed, food product, diet supplement or food additive as defined in claim 8 or 9 to manufacture a drug to reduce the expression of one or more pro-inflammatory genes in a cell or cells in a subject.

According to the nineteenth aspect of the invention, Bacteroidetes as defined in claims 1 or 5 or a composition as defined in claims 2 or 3, or a pharmaceutical composition as defined in claims 4 or 5, or a food supplement as defined in claims 4 or 5. Defined in claims 6 or 7, a feed, food product, diet supplement, or food additive as defined in claims 8 or 9 for the manufacture of a drug to increase the proportion of regulatory T cells (Tregs) in the gastrointestinal tract or a segment of the gastrointestinal tract.

<h3 dir="rtl">10 Brief explanation of the drawings</h3>

The invention is described by referring to the forms of accompaniment.

where:

Figures 1A, 1B, and 1C: Illustrate the attenuation of colitis by expansion of regulatory T cells with Bacteroidetes vulgaris strain BT2013 in a model of colitis induced by Dext Arn 15 sodium sulfate.

Figures 2a and 2b show that Bacteroidetes strain BT2013 does not affect regulatory T cells, but it affects effector T cells in conventional mice.

Figures 3A and 3B: show the activity of the myeloperoxidase enzyme in the ileum (A) and cecum (B) of mice that were given a dose of dextral sodium sulfate with or without a daily intake of 20 Bacteroidetes bacteria.

Figures 4a and 4b: show histological pathology in the ascending colon of 6/C57Bl female mice that were given a dose of Sodium dextran sulfate (a) or Sodium dextran sulfate and B. thetaiotaomicron (b).

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Figure 5 shows the average histopathology results of ascending colon tissue from the Arn class colonized with Bacteroidetes strains E1 and BT2013 during colitis induced by Dext Arn sodium sulfate.

Figure 6: shows the expression of the proinflammatory genes (IL-1β and IL-6) and the antagonist gene

5 For inflammation (IL-10) in the ascending colon of mice treated with Bacteroides difficile strains E1, E2, and BT2013.

Figure 7: Expression of IL-8 in Caco-2 cells incubated with monoether acetate.

Mono-methylpropylene glycol acetate (PMA)

E1, E2, and BT2013 bacterial cells.

<h3 dir="rtl">10 Detailed description:</h3>

The present invention is based on the finding that the BT2013 strain of Bacteroides bacterium has more potent anti-inflammatory effects compared to standard Bacteroides strains.

Bacteroidetes strain BT2013 was deposited under registration number 42341 on 3 December 2014 with the National Collections of Industrial, Food and Marine Bacteria at NCIMB Ltd, Bldg.

<p dir="rtl">15 Ferguson Building, Craibstone Estate, Bucksburn, Aberdeen, United Kingdom, AB21 9YA. The deposit was made under the terms of the Treaty of Budapest. Filed by Life Sciences GT Biologics Ltd</p>

GT Company name changed. Innovation Building, Aberdeen, AB25 2ZS, Scotland)

Biologics Ltd later to 4D Pharma Research Limited.

<p dir="rtl">20 Derivative:</p>

The present invention includes derivatives of the deposited strain. The term “derived” includes daughter strains (offspring) or stains cultured (sub-cloned) strains.

From the original breed but modified in some way (including at the genetic level), without change

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Negative for biological activity, meaning that the derived strain will have at least the same immunomodulatory activity as the original strain BT2013.

Biotypes:

The genome sequence of strain BT2013 is available as sequence identification number: 1.

<p dir="rtl">5 It is also expected that bacterial strains that are bacterial biotypes filed under registration number 42341 with the National Collections of Industrial, Food, and Marine Bacteria (NCIMB 42341) will be effective for the treatment or prevention of inflammatory disorder and/or autoimmune disorder. /or allergic disorder. A biotype is a closely related strain that has the same or 10 very similar physiological and biochemical properties.</p>

In certain embodiments, the relevant bacterial strain for use in the invention has a 16s rRNA ribosomal RNA sequence that is at least 95%, 96%, or 97% identical to the 16s rRNA sequence of bacteria filed under NCIMB registration number 42341. %, 98%, 99%, 99.5%, or 99.9%.

<p dir="rtl">15 Alternatively, bacterial strains that are biotypes of bacteria filed under NCIMB 42341 and suitable for use in the invention may be identified by sequencing other nucleotide sequences of bacteria filed under NCIMB 42341. For example, a substantially complete genome sequence may be determined and the biotype strain of interest for use in the invention may have sequence homology of at least 95%, 96%,</p>

<p dir="rtl">20 97%, 98%, 99%, 99.5%, or 99.9% across at least 80% of your complete genome</p>

(e.g., at least 85%, 90%, 95%, or 99%). Other sequences suitable for use in identifying biotype strains may include heat shock protein 60 hsp60 or repeat sequences such as GTG (5, ERIC, BOX) or Masco et al. REP)

<p>2003). They may be strains (Systematic and Applied Microbiology, 26:557-563).</p>

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Biotype having sequences with at least 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence homology to the corresponding sequence of the bacterium deposited under registration number

(NCIMB 42341)

In certain embodiments, the bacterial strain for use in the invention has a homologous genome

<p dir="rtl">5 Sequence identification number: 1. In preferred embodiments, the bacterial strain concerned for use in the invention has a genome with at least 90% sequence homology (e.g., 92%, 94%, 95%, 96%, 97%, 98% %, 99%, or 100%) to define the sequence number: 1 through at least 60% (for example, 65%, 70%, 75%, 80%, 85%, 95%, 96%, 97%, 98%, % 99, or 100%) of sequence definition number: 1. For example, the strain might be</p>

<p dir="rtl">10 The bacterium of interest for use in the invention has a genome with at least 90% sequence homology to SEQ ID NO: 1 over 70% of SEQ ID NO: 1, or at least 90% sequence homology to SEQ ID NO: 1 over 80% of SEQ ID: 1. Number: 1, or at least 90% sequence identity to sequence definition Number: 1 through 90% of sequence definition Number: 1, or at least 90% sequence identity to sequence definition Number: 1 through 100% of sequence definition.</p>

<p dir="rtl">15 No.: 1, or at least 95% sequence identity to Sequence Identification No.: 1 over 70% of Sequence Identification No.: 1, or at least 95% sequence homology to Sequence Identification No.: 1 over 80% of Sequence Identification No.: 1, Or at least the same sequence by 95% to define the sequence number: 1 via 90% of the definition of the sequence number: 1, or at least the same sequence by 95% to define the sequence number: 1 through 100% of the definition of the sequence number: 1, or at the least similar Sequence by</p>

<p dir="rtl">20 98% of the definition of sequence number: 1 over 70% of the definition of sequence number: 1, or at least similarity.</p>

Sequence identification number: 1 has a 98% sequence identity over 80% of sequence identification number: 1, or at least 98% sequence identity to sequence identification number: 1 through 90% of sequence identification number: 1, or at least 98% sequence identity. To define sequence number: 1 through 100% of sequence definition number: 1.

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Alternatively, biotype strains of bacteria deposited under NCIMB No. 42341 that are suitable for use in the invention may be identified by use of NCIMB No. 42341, restriction fragment analysis and/or rice polymorphism chain reaction analysis, for example by The use of polymorphism throughout the pieces amplifies the brilliance and imprint of the element

<p dir="rtl">5 Deoxyribonucleic acid (rep)-PCR, or</p>

Protein profiling, or the partial chain of ribosomal DNA, 16S rDNA or 23S rDNA.

In certain embodiments, strains that are biotypes of bacteria deposited under NCIMB registration number (42341) and suitable for use in the invention are strains that give the same type as the bacteria deposited.

<p dir="rtl">10 Under registration number (NCIMB 42341) when analyzed by amplified RNA restriction analysis, for example when using the restriction enzyme for Sau3AI)</p>

Example methods and guidance see, for example, Srůtková et al.

<p>2011). Alternatively, the strains are known as J. Microbiol. Methods, 87(1):10-6.</p>

Probiotics as strains possess the same carbohydrate fermentation patterns as the deposited bacteria

<p dir="rtl">15 Under registration number (NCIMB 42341).</p>

Bacterial strains that are biotypes of bacteria filed under registration number (NCIMB 42341) and useful in the compositions and methods of the invention may be identified using any appropriate method or strategy. For example, bacterial strains that have similar growth patterns, metabolic type and/or surface antigens to the bacteria filed under registration number (NCIMB 42341) may be useful in

<p dir="rtl">20 Sister Raa. The biotype strain will have immunomodulatory activity similar to the NCIMB strain</p>

42341. For example, the biotype strain will exert similar effects on models of SDS-induced colitis and similar effects at the level of regulatory T cells (Tregs), myeloperoxidase enzymatic activity, proinflammatory gene expression, and colon tissue pathology demonstrated in functional assays, which It may be knowledge

<p dir="rtl">25 Using the protocols described in Functional Assays.</p>

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Arbat Arbat:

Bacteroidetes strain BT2013 may be used for the treatment and/or prophylaxis of asthma in subjects where the disease is an inflammatory and/or autoimmune infection.

<p dir="rtl">5 In one embodiment, the disturbance affects the gastrointestinal tract, a section of the gastrointestinal tract, the liver, liver cells, immune cells, epithelial cells, and / or epidermal cells, and / or neuronal cells, and / or endothelial cells, and / or fibroblasts, and / or pancreas and / or pancreatic cells</p>

<p dir="rtl">10 cells such as the islets of Langerhans.</p>

Examples of sections (parts) of the digestive canal include the esophagus, alimentary canal, stomach, intestine such as the small intestine, such as the duodenum, jejunum, and ileum, and/or large intestine, such as the caecum, ascending colon, and transverse colon.

<p dir="rtl">15 transverse colon, descending colon, and sigmoid colon.</p>

Examples of epithelial cells include intestinal epithelial cells. Examples of immune cells include dendritic cells, monocytes/macrophages, T cells, and neutrophils

.neutrophils

<p dir="rtl">20 In one embodiment, the disorder is selected from a group consisting of:</p>

Organ-related disorders such as irritable bowel syndrome, inflammatory bowel disease including Crohn's disease and ulcerative colitis, necrotizing enterocolitis, pouchitis, coeliac disease, and multiple sclerosis. brain, disease

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Type I diabetes, Goodpasture's syndrome, Hashimoto's thyroiditis, chronic active hepatitis, cardiomyopathy, cardiomyopathy, uveitis, rhinitis.

<p dir="rtl">5 Systemic disorders such as rheumatoid arthritis</p>

rheumatoid arthritis, systemic lupus erythematosus, cutaneous scleroderma, psoriasis, atopic dermatitis, vitiligo-like syndrome, multiple sclerosis, alopecia areata, sarcoidosis, polymyositis and combinations

<p dir="rtl">10 Of which.</p>

In one aspect, the disorder affects the intestines.

In one aspect, arthritis is an inflammatory arthritis. For example, irritable bowel syndrome is an inflammatory bowel syndrome such as Crohn's disease.

In one aspect, seizures are autoimmune seizures. for example

<p dir="rtl">15 For example, an autoimmune disorder is selected from a group consisting of ulcerative colitis, pouchitis, rheumatoid arthritis, psoriasis, multiple sclerosis, type 1 diabetes, allergies (including celiac disease), atopic dermatitis, and synovitis. Mucous nose.</p>

Submissive:

<p dir="rtl">20 In one embodiment, the subject is a monogastric animal.</p>

Examples of monogastric animals include poultry, humans, rats, pigs, dogs, cats, horses, and rabbits.

In another embodiment, the subject person is a mammal such as a monogastric mammal.

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Examples of monogastric mammals include carnivores (such as humans, rats, and pigs), carnivores (such as dogs and cats), and herbivores (such as horses and rabbits).

Preferably, the submissive is a human being.

In one aspect, the submissive is experiencing a choice of a group consisting of a group of subjects

<p dir="rtl">5 Inflammatory bowel disease, colitis, rheumatoid arthritis, psoriasis, multiple sclerosis, type 1 diabetes, celiac disease, atopic dermatitis, rhinitis, irritable bowel syndrome, ulcerative colitis, pouchitis, Crohn's disease, indigestion. Occupational, atopic, necrotizing enterocolitis, non-alcoholic fatty liver disease, gastrointestinal infection, and combinations thereof. For example, the submissive suffers from intestinal distress</p>

<p dir="rtl">10 Inflammatory.</p>

Editing/organizing:

The terms “amendment” and “regulation” may be used interchangeably throughout this document.

In one embodiment, strain BT2013 of Bacteroidetes bacterium is used to modify the inflammation of a cell, tissue or organ in a subject.

<p dir="rtl">15 In one embodiment, the term “modulation” means increasing, inducing, enhancing, and/or activating. In an alternative embodiment, the term “modulation” refers to reduction, reduction, and/or inhibition.</p>

In one embodiment, the term “regulation” refers to positive regulation. In an alternative embodiment, the term “regulation” refers to negative regulation.

In one embodiment, strain BT2013 of Bacteroidetes as described herein

<p dir="rtl">20 The document refers to the inflammation of a cell, tissue or organ. For example, inflammation of the gastrointestinal tract, a section (any part) of the gastrointestinal tract (e.g. intestine), liver, hepatocytes, epithelial cells, epidermal cells, and/or neurons, And/or endothelial cells, and/or fibroblasts, and/or pancreatic cells (such as islets of Langerhans).)</p>

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In one example, inflammation of the gastrointestinal tract or part of it (such as the intestine) is reduced.

In another example, inflammation is reduced by the immune cells of a tissue or organ.

In another example, inflammation is reduced by epithelial cells of a tissue or organ.

The term “inflammation” as used herein refers to one or more of the following: redness, swelling, pain,

<p dir="rtl">5 Pain, heat, or disturbance of the function of a cell, tissue or organ due to an inflammatory process initiated by an overreaction of the immune system.</p>

In one embodiment, the number of inflamed cells in a subject is at least 10%, 20%, 30%, 40%, or 50% lower after administration of a polypeptide, polynucleotide, or host cell as described herein when compared with the number of inflamed cells in a subject. Before giving the submissive the strain

. BT2013 10

In one embodiment, the amount of inflamed tissue or organ in a subject is at least 10%, 20%, 30%, 40%, or 50% less after administration of strain BT2013 when compared to the amount of tissue or organ inflamed in a subject before administration of strain BT2013 to the subject.

In one embodiment, strain BT2013 reduces inflammation by epithelial cells of a tissue or organ.

<p dir="rtl">15 For example, epithelial cells are epithelial cells of the gastrointestinal tract or part of it (such as the intestine).</p>

Without wanting to be limited by theory, the BT2013 strain increases the production of T cells (such as regulatory T cells that may hereafter also be referred to as regulatory T cells) in subjects. This increase in the numbers of regulatory T cells may counteract the effects of other effector T cells (referred to hereafter as Tregs).

<p dir="rtl">20 Also known as T effector cells (Teffs) (such as Th17, Th1, and Th2 that drive inflammation,</p>

Autoimmune and allergic/atopic conditions. In Crohn's disease and ulcerative colitis, the balance between effector T cells/regulatory T cells is missing.

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In one embodiment, T cell production in the subject is increased such that there are at least 10%, 20%, 30%, 40%, or 50% more T cells, or greater than 100% more T cells after administration of the polypeptide or polynucleotide. Or host cell as described here when compared with the number of T cells in the subject prior to administration

<p dir="rtl">5 Submissive breed. BT2013</p>

Intestine barrier integrity

In one embodiment, strain BT2013 is used to improve the intestinal barrier integrity of a subject.

The term “improved gut barrier integrity” as used herein refers to a reduction in the numbers and/or types of microorganisms that spread from the intestine to other cells in a subject after administration of strain 10 BT2013 when compared to the numbers and/or types of microorganisms that spread from Intestines to cells

Others were incubated before administration of strain BT2013 as described here.

In one embodiment, the numbers of microorganisms that spread from the intestine to other cells in a subject are at least 10%, 20%, 30%, 40%, or 50% lower after administration of strain BT2013 when compared to the numbers of microorganisms that spread from the intestine to Other cells in 15 subjects before administration.

In one embodiment, there are at least 5%, 10%, 15%, or 20% fewer types of microorganisms that spread from the intestine to other cells in a subject after administration of strain BT2013 when compared to the types of microorganisms that spread from the intestine to other cells. In submissive before giving.

20 Intestine disruption:

In one embodiment, strain BT2013 is used to reduce rupture of an intestine (e.g., large intestine) in a subject (e.g., a subject suffering from inflammatory bowel syndrome).

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The term “subject bowel rupture” as used here refers to an effect on the integrity of the mucosal epithelium, an effect on the number of goblet cells present in the epithelium, and/or an effect on the number of infiltrating immune cells in the lamina propria.

In one embodiment, strain BT2013 reduces or prevents disruption of mucosal epithelial integrity and/or reduces

<p dir="rtl">5 Or prevent the reduction in the number of goblet cells in the epithelium and/or reduce or prevent the infiltration of immune cells in the lamina propria.</p>

In one embodiment, the reduction in mucosal epithelial integrity is at least a 5%, 10%, 15%, or 20% reduction in the number of bacteria crossing from the intestinal lumen to enterocytes after administration of strain BT2013 compared to the numbers of bacteria. Which expresses a shine

<p dir="rtl">10 Intestinal to enterocytes in subject prior to administration.</p>

In one embodiment, the reduction in the number of goblet cells in the epithelium is a reduction of at least 2%, 5%, 10%, 15%, or 20% in the number of goblet cells in the epithelium in a subject after administration of strain BT2013 compared to the number of cells sepals in the epithelium in the subject before administration.

<p dir="rtl">15 In one embodiment, the reduction in the infiltration of immune cells into the lamina propria is such that over a specified period of time (e.g., 24 hours) there is a reduction of at least 5%, 10%, 15%, 20%, or 30% in the numbers of immune cells (e.g., cells T cells) that cross into lamina propria cells after administration of the BT2013 strain compared with the numbers of immune cells (for example, T cells) that cross into the lamina propria in a subject before administration.</p>

<p dir="rtl">20 Inflammation-activating genes and barrier integrity genes</p>

In one embodiment strain BT2013 is used to regulate the expression of one or more proinflammatory genes and/or one or more barrier integrity genes in a subject cell or cells.

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In one embodiment, the term “regulation” refers to positive regulation in the expression of one or more proinflammatory genes. In an alternative embodiment, the term “regulation” refers to negative regulation in the expression of one or more proinflammatory genes.

In one embodiment, strain BT2013 regulates the expression of one or more activating genes

<p dir="rtl">5 Inflammation in a cell or cells is negatively regulated.</p>

The term “inflammation-promoting gene” as used here refers to a gene that when expressed, stimulates inflammation. Examples of proinflammatory genes include, but are not limited to, the following: IL27, IL23, IL22, IL21, IL17, IL13, IL12, IL8, IL6, IL5, IL4, IL1-β, interferon, CXCL12, CXCL10, CXCL5, CCL20, CCL5, CCL3, CCL2,

<p dir="rtl">10 CXCL13 and TNF-α.</p>

In one embodiment, the proinflammatory gene is selected from a pool consisting of IL6, IL1-β, and IL8.

In one embodiment, the expression level of, for example, mRNA of one or more proinflammatory genes is reduced, i.e., negatively regulated, such that the level is at least 10%, 20%, 30%, 40%, or 50% lower after administration of strain BT2013 compared to the level in the subject. Before administration.

<p dir="rtl">15 The term “barrier integrity gene” as used here refers to a gene that when expressed has a role in intestinal barrier function such as barrier repair and preventing microorganisms from crossing the barrier. Examples of barrier integrity genes include genes encoding Retnlg|Retnlb, Hsd17b2, Hsd11b2, Defa24, Si, and Nr1d1|Thra.</p>

In one embodiment, the term “regulated” refers to positive regulation in the expression of one or more of

<p dir="rtl">20 Barrier integrity genes. In an alternative embodiment, the term “regulated” refers to negative regulation in the expression of one or more barrier integrity genes.</p>

In one embodiment, strain BT2013 positively regulates the expression of barrier integrity genes in a cell or cells.

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In one embodiment, a barrier integrity gene selects from a pool consisting of Si, Retnlg|Retnlb, Hsd17b2, Hsd11b2, Defa24, and Nr1d1|Thra.

In one embodiment, the expression level (e.g., mRNA level) of one or more barrier integrity genes is increased (i.e., positively regulated) such that the level 5 is higher after administration of strain BT2013 by 10%, 20%, 30%, 40% or 50% at least

Compared with the level in the subject before administration.

Gut

The parts of the alimentary canal include the esophagus, stomach, intestine (e.g. small intestine (e.g. duodenum, jejunum, ileum)) and/or large intestine (e.g. caecum, ascending colon

<p dir="rtl">10 ascending colon, transverse colon, descending colon, and sigmoid colon.</p>

Throughout this document, the term “large intestine” may be used interchangeably with the term “colon.”

In one embodiment, strain BT2013 is used to improve gut health in a subject.

The term “improving gut health” as used here refers to reducing the level of

<p dir="rtl">15 Inflammation of the gastrointestinal tract or part of it and/or improvement of the intestinal microbiota.</p>

In one embodiment, the level of inflammation in the gastrointestinal tract is at least 10%, 20%, 30%, 40%, or 50% lower after administration of strain BT2013 compared to the level of inflammation in the gastrointestinal tract of a subject prior to administration.

In one embodiment, strain BT2013 is used to improve the intestinal microbiota in a subject.

<p dir="rtl">20 The term “gut microbiota” as used here refers to microorganisms that live in the gastrointestinal tract of host animals. These microorganisms perform a wide range of metabolic, structural, protective and other beneficial functions.</p>

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As used herein, the term “improvement of the intestinal microbiota” refers to increasing the number and/or

The type of desired microorganisms present in the subject's gut (e.g. the host), and/or increased activity

The desired microorganisms are mentioned in terms of their metabolic, structural, protective and beneficial functions

Other. The term “improvement of the intestinal microbiota” may also refer to reducing the number and/or type

<p dir="rtl">5 Undesirable microorganisms present in the intestines of a subject (eg the host), and/or reducing the activity of said undesirable microorganisms in terms of their metabolic, structural, protective and other beneficial functions.</p>

Desirable microorganisms in the intestine of a host are those microorganisms that have a protective and beneficial function. Firmicutes and Bacteroides bacteria are examples of desirable microorganisms

<p dir="rtl">10 The intestine of a host.</p>

Unwanted host intestinal microorganisms are those microorganisms that can interfere with the metabolic, structural, protective and other beneficial functions of desirable intestinal microorganisms that have protective and beneficial functions. Additionally or alternatively, unwanted microorganisms are those that cause, for example, inflammation and/or diarrhoea. Escherichia

<p dir="rtl">15 coli is an example of an unwanted microorganism in a host's intestine.</p>

For example, a change in the balance of the microbiota may occur between desirable microorganisms such as Firmicutes and Bacteroidetes and undesirable microorganisms such as E. coli, enterotoxin-producing E. coli, enteropathogenic E. coli, intestinal-invasive E. coli, intestinal bleeding E. coli, and aggregated Escherichia coli

<p dir="rtl">20 Intestinal (intra-intestinal) in subjects with inflammatory bowel disease once strain BT2013 is administered to the subject.</p>

In one embodiment, the number of desired microorganisms (e.g., Firmicutes and Bacteroidetes) present in the intestine of a subject (e.g., the host) is increased, such that the number of microorganisms is at least 10%, 20%, 30%, 40%, or 50% higher, or Higher than 100% after administration

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Strain BT2013 compared with the level in the subject before administration. In addition, or alternatively, the types of desired microorganisms (e.g. Firmicutes and Bacteroidetes) present in a subject's intestine (e.g. the host) increase, such that there are at least 2%, 5%, 10% or 15% more types of microorganisms After giving the strain BT2013 compared to the types in the subject before

<p dir="rtl">5 Giving.</p>

In one embodiment, the number of unwanted microorganisms (e.g., E. coli, enterotoxin-producing E. coli, enteropathogenic E. coli, enteroinvasive E. coli, enterohemorrhagic E. coli, and intestinal aggregated E. coli) present in the intestine of a subject (e.g., the host) is reduced (, so that the number of microorganisms is 10% less or

<p dir="rtl">10 At least 20%, 30%, 40%, or 50%, after giving the BT2013 strain compared to</p>

Level in subject before administration. In addition, or alternatively, unwanted microorganisms such as E. coli, enterotoxin-producing E. coli, enteropathogenic E. coli, intestinal invasive E. coli, intestinal bleeding E. coli, and intestinal-aggregating E. coli present in the subject's intestines are reduced. For example, the family

<p dir="rtl">15 So that there are at least 1%, 2%, 5%, or 10% fewer types of unwanted microorganisms after giving the BT2013 strain compared to types in the condition before administration.</p>

Conservatism:

In one embodiment, strain BT2013 of Bacteroidetes bacterium is capsular.

In another embodiment, a pharmaceutical composition comprising strain BT2013 is a capsular.

<p dir="rtl">20 In another embodiment, a dietary supplement comprising strain BT2013 is a preservative.</p>

In another embodiment, a feed, food product, diet supplement, or food additive as described herein is preserved.

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The term “protected” as used herein refers to a means of protecting the incompatible strain BT2013 from the environment by physical separation so that it can be delivered to the target site (e.g. intestine) without degradation or significant degradation so that strain BT2013 can affect the target site. An example of this is an enteric-coated capsule or a resistant capsule

<p dir="rtl">5 Intestinal.</p>

Even when the purpose of the enclosure is to isolate the breed from its surrounding environment, the protective covering or covering must be torn at the time of the desired action. The coating or protective coating is typically torn apart by the application of chemical and physical influences such as pressure, enzymatic attack, chemical reaction and physical fragmentation.

<p dir="rtl">10 For example, preservation ensures that the strain can be ingested such that the microorganisms can be delivered to the target site (eg intestine) in an amount effective to produce an effect at the target site.</p>

Pharmaceutical composition:

In one embodiment, a pharmaceutical composition comprising microorganisms of strain BT2013 and optionally a pharmaceutically acceptable excipient, carrier, or diluent.

<p dir="rtl">15 A pharmaceutical composition can be any pharmaceutical composition. In one aspect, the pharmaceutical composition is intended for oral, gastrointestinal, or rectal administration. For example, the formulation could be an edible formulation. The term “edible” means a substance approved for human consumption or animal consumption.</p>

Pharmaceutical compositions may be for human or animal use in human and veterinary medicine.

<p dir="rtl">20 Examples of such excipients suitable for many different forms of formulations can be found</p>

“Handbook of Pharmaceutical Excipients, 2nd Pharmaceutical Excipients Described here in Edition, (1994), Edited by A Wade and PJ Weller.

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Pregnancies or diluents acceptable for therapeutic use are well known in the pharmaceutical art and are described

Remington's Pharmaceutical Sciences, Mack Publishing, Inc., for example. (AR Gennaro edit. 1985)

Examples of suitable carriers include lactose, starch, glucose, and methyl

<p dir="rtl">5 Methyl cellulose, magnesium stearate, mannitol, sorbitol and the like.</p>

Examples of suitable diluents include one or more of: water, ethanol, glycerol, propylene glycol, glycerin, and combinations thereof.

The choice of carrier, excipient or pharmaceutical diluent can be selected accordingly

<p dir="rtl">10 for the route of administration in question and standard pharmaceutical practice. Pharmaceutical compositions may include any binder(s), lubricant(s), suspending agent(s), coating agent(s), solubilizing agent(s). (s) Suitable as, or in addition to, a carrier, excipient or diluent.</p>

Examples of suitable binders include starch, gelatin, natural sugars such as glucose, non-anhydrous lactose,

<p dir="rtl">15 Free-flowing lactose, beta-lactose, corn sweeteners, natural and artificial gums, such as acacia gum, tragacanth gum or sodium alginate, carboxymethyl cellulose and polyethylene glycol.</p>

Examples of suitable lubricants include sodium oleate, sodium stearate, magnesium stearate, and sodium benzoate.

<p dir="rtl">20 sodium benzoate, sodium acetate, sodium chloride and the like.</p>

Preservatives, stabilizers, dyes and even flavorings may be available in the pharmaceutical formulation. Examples of preservatives include sodium benzoate and sorbic acid

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acid, and esters of p-hydroxybenzoic acid. Antioxidants and suspending agents may also be used

In one aspect, the microorganisms in the pharmaceutical formulation of strain BT2013 are capsular.

The pharmaceutical composition may be in solution or solid form depending on the use and/or method

<p dir="rtl">5 Application and/or method of administration.</p>

As used herein, the term “drug” includes drugs for human and animal use in human and veterinary medicine. In addition, the term “drug” as used herein means any substance that produces a therapeutic and/or beneficial effect. The term “medicine” as used here is not necessarily limited to substances, which need marketing approval but may include substances that can be used in

<p dir="rtl">10 Cosmetics, nutritional preparations with health benefits, and foods (including</p>

(e.g. feed and beverages), probiotic cultures, nutritional supplements and natural medicines. In addition, the term “drug” as used herein includes a product designed to be incorporated into an animal feed, for example livestock feed and/or pet food.

Food Supplements :

<p dir="rtl">15 Food grade carriers, diluents and excipients include those suitable for human or animal consumption and those used as a standard in the food industry. Typical food grade carriers, diluents and excipients will be familiar to those experienced in the art.</p>

In one embodiment, a food supplement comprises a microorganism of strain BT2013 or a host cell comprising an expression vector comprising said polynucleotide sequence and an excipient, food-acceptable carrier or diluent 20.

In one example, the microorganism of strain BT2013 is capsular.

Feed/products

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Another aspect of the invention relates to feeds, food products, diet supplements and food additives containing microorganisms of strain BT2013.

The terms “feed,” food product,” food additive,” and “diet supplement” as used herein are intended to cover all consumable products that may be in solid form or

5 Gel or liquid.

The term “food product” is used in a broad sense and covers human food as well as animal food (i.e. feed). In one aspect, a food product for human consumption. Examples of food products include dairy products (e.g. milk, cheese, beverages containing whey protein, beverages Milk, lactic acid bacteria drinks, yogurt, yogurt drink (,

<p dir="rtl">10 AZT Vanity Products, Beverages and Beverage Powders.</p>

The “feed,” food product, food additive, and “diet supplement” may be in the form of a solution or a solid - depending on the use, method of application, and/or method of administration.

As used herein, the term “diet supplement” includes a formulation that is or may be added to a food or feed product as a dietary supplement. The term "diet supplement" refers to the following:

<p dir="rtl">15 Also used here are formulations that can be used at low levels in a variety of products that require gelatinization, texturing, stabilization, suspension, coating, and structuring, maintaining juiciness and improving mouthfeel without adding viscosity.</p>

Suitable food products may include, for example, functional food products, nutritional formulas, pet food, livestock feed, health foods, fodder and the like. in

<p dir="rtl">20 In one aspect, the food product is a health food.</p>

As used herein, the term “functional food product” means a food capable of providing not only a nutritional effect but also capable of delivering a beneficial effect to the consumer. Accordingly, functional foods are regular foods with ingredients or elements (such as those described here) incorporated into them that

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It gives food a specific functional effect, such as a medical or physiological benefit, other than its purely nutritional effect.

Examples of specific food products applicable to the present invention include milk-based products, ready-to-eat desserts, powders intended to be reconstituted with, for example, milk or

<p dir="rtl">5 Water, chocolate milk drinks, sprouted barley drinks, ready-to-eat dishes, instant dishes or beverages for humans or food compositions constituting a complete or partial diet prepared for pets or livestock.</p>

In one aspect, a feed, food product, diet supplement or food additive according to the present invention is intended for humans, pets or livestock such as monogastric animals. may be

<p dir="rtl">10 The feed, food product, diet supplement or food additive intended for selected animals</p>

From the group that consists of dogs, cats, pigs, horses or poultry. In another embodiment, the food product, diet supplement or food additive is intended for an adult species, particularly an adult human.

The term “milk-based product” as used herein means any liquid, semi-solid milk15 or serum-based product of varying fat content. It can be a milk-based product,

For example, cow's milk, goat's milk, ewe's milk, skimmed milk, whole milk, milk reconsolidated from milk powder and whey without any processing, or a processed product such as yogurt, curdled milk, curds, sour milk, whole sour milk. , ghee, and other sour milk products. Another important group includes milk drinks such as whey drinks, fermented milk, condensed milk, and infant or child formula; Flavored dairy, ice cream,

Foods containing milk, such as candy.

Feed, food products, diet supplements or food additives in the present invention may be, or may be added to, food supplements also referred to herein as diet supplements, food supplements or food additives.

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Feeds, food products, diet supplements or food additives according to the present invention may also be used in animal nutrition (e.g. in feeding pigs), particularly in the early weaning period and the fattening period. Feeds, food products, diet supplements or food additives are expected to enhance Nutrition enhances immune function, reduces and prevents infectious diseases, and changes the composition of the macular microflora

<p dir="rtl">5 Beneficially, it improves animal growth and performance, for example by increasing feed conversion efficiency.</p>

In one embodiment the feed, food product, diet supplement or food additive is preserved.

Live biotherapeutic product:

Microorganisms of strain BT2013 may be used in or as a live biotherapeutic product.

In one aspect, a live biotherapeutic product is an orally administered formulation of

<p dir="rtl">10 Metabolically active bacteria, i.e. live and/or lyophilized, or non-living bacteria killed by heat, irradiated or hydrolyzed. The live biotherapeutic product may contain other ingredients. The live biotherapeutic product can be administered orally i.e. in tablet, capsule or powder form. The live biotherapeutic product may also include other bacterial species, for example, R. hominis. Preferably products that contain R. hominis bacteria, as they are anaerobic. Other components (eg</p>

<p dir="rtl">15 Vitamin C, for example) may be included in the form of oxygen scavengers and substrates (such as those that improve colonization and survival in a living cell). Alternatively, the live biotherapeutic product according to the present invention may be administered orally as a food or food product. Food, such as milk or whey-based fermented dairy products, or as a pharmaceutical product.</p>

The appropriate daily dose of bacteria in a live biotherapeutic product ranges from approximately 1 x 310

<p dir="rtl">20 to approximately 1 x 1210 CFU; For example, from about 1×710 to about 1×1010 CFU; In another example from about 1 x 610 to about 1 x 1010 colony forming units.</p>

In one aspect, the live biotherapeutic product contains bacterial species and/or cellular components thereof, as active ingredients in an amount ranging from about 1 x 610 to about 1 x 1210

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CFU/crm, relative to the weight of the formula; For example, from about 1×810 to about 1×1010 CFU/carm. Typically, the live biotherapeutic product is optionally combined with at least one appropriate biologic compound. The probiotic is usually an indigestible carbohydrate such as an oligosaccharide or polysaccharide, or a sugar alcohol, which is not

<p dir="rtl">5 It is broken down or absorbed in the upper gastrointestinal tract. Well-known probiotics include commercial products such as inulin and T-arnes galacto-oligosaccharides.</p>

In one aspect, the live biotherapeutic product according to the present invention includes a probiotic in an amount ranging from about 1 to about 30% by weight, relative to the total weight composition, (e.g. from 5 to 20% by weight). From a group consisting of: a few compounds

<p dir="rtl">10 Fructose oligosaccharides (or FOS), short-chain fructose oligosaccharides, inulin, isomalt-oligosaccharides, pectins, xyl oligosaccharides (or Cultivables, polydextrose, D-tagatose, acacia, carob, oat, and citrus fibers. In one aspect, probiotics are short-chain fructose oligosaccharides (for simplicity).</p>

<p dir="rtl">15 Herein described below as FOSs-cc(; the short-chain fructose oligosaccharides mentioned are non-digestible carbohydrates, generally obtained by the conversion of beet sugar and including a sucrose molecule to which the three glucose molecules are linked.</p>

Giving:

Pharmaceutical compositions, nutritional supplements, feed, food products, diet supplements or food additives 20 may be adapted in accordance with the present invention for oral or rectal routes of administration,

Or vaginal, or injection, or intramuscular, or intraperitoneal, or intraarterial, or intrathecal, or intrabronchial, or subcutaneous, or intradermal, or intravenous, or through the nose, or buccal, or under the tongue.

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In one aspect, pharmaceutical compositions, nutritional supplements, feed, food products, diet supplements or food additives according to the present invention are adapted for oral, rectal, vaginal, injectable, nasal, buccal, or subcutaneous routes of administration. the tongue.

On the other hand, pharmaceutical formulations, nutritional supplements, feed, food products,

<p dir="rtl">5 Diet supplements or food additives according to the present invention are adapted for oral administration.</p>

For oral administration, tablets, tablets, lozenges, softgels, drops and capsules are used.

Other forms of administration include solutions or emulsions that can be injected intravenously, intraarterially, intrathecally, subcutaneously, intraepidermally, intraperitoneally or intramuscularly and which are

<p dir="rtl">10 Prepared from sterile or autoclavable solutions. Pharmaceutical compositions according to the present invention may also be in the form of suppositories, vaginal suppositories, and suspensions. Pharmaceutical compositions, nutritional supplements, feed, food products, diet supplements or food additives may be formulated in unit dose form, that is, in the form of separate parts containing a unit dose, a multiple unit dose, or a subunit of a unit dose.</p>

15 Dosage:

A person with ordinary experience in the art can easily determine the appropriate dose of strain BT2013 to administer to a subject without unnecessary experimentation. Typically, the physician will determine the actual dosage that will be most appropriate for the individual patient and the dosage will depend on many factors including the activity of the strain used, metabolic stability and length of action.

<p dir="rtl">20 These include breed, age, body weight, general health, gender, diet, method and time of administration, excretion rate, drug combination, severity of specific conditions, and the individual being treated. The doses disclosed herein are representative doses for an average condition. There can of course be individual cases where higher or lower dosage ranges are required, which are within the scope of this invention.</p>

Combinations:

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In one aspect, the microorganism of strain BT2013 is administered in combination with one or more other active agents. In these cases, the microorganisms of strain BT2013 may be administered sequentially, simultaneously or sequentially with one or more other active agents.

Functional assays:

<p dir="rtl">5 Model inside a living cell:</p>

Ern 6/C57BL mice (6 weeks old) were used to evaluate the therapeutic effect of Bacteroides strains E2, E1 and BT2013 during colitis induced by Dext Ern sodium sulfate. Arn mice were colonized by one of the Bacteroides strains before treatment with Dext Ern sodium sulfate. The animals were euthanized and a small intestine tissue sample was collected for immunological analysis by flow cytometry and myeloperoxidase enzyme activity measurements

The ascending colon was divided into equal parts and transferred to neutral buffered formalin (NBF; Sigma-Aldrich).

For histological analysis or Ambion (RNAlater) for molecular analysis.

Flow cytometry analysis of T cell populations in the lamina propria of the small intestine was performed (Figure 1 and Figure 2). Treatment with dextrine sodium sulfate alone did not affect

<p dir="rtl">15 And Bacteroides difficile on the total ratio of the group -CD3+CD4+CD8. The groups affected by DES alone and Bacteroidetes were regulatory T cells (*+CD25+FoxP3 and *+FR4hiCD25*) and effector T cells (*+FR4loCD25) (Figure 1 and 2). The percentage of regulatory T cells increased in mice treated with the BT2013 strain. of Bacteroidetes bacterium compared to sodium sulfate dextrin alone</p>

<p dir="rtl">20 The E1W strain has no effect on regulatory T cells.</p>

(Figure 1). The effects of strain BT2013 on regulatory T cells were only evident in mice co-treated with dextran sodium sulfate. The strain had no effect on regulatory T cells in untreated mice but affected the effector T cell population (Figure 1). 2(.

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Myeloperoxidase activity was determined in the ileum and cecum (Figure 3A and 3B). Myeloperoxidase is a proinflammatory enzyme stored in the apophilic granules of neutrophil granulocytes. Myeloperoxidase is used as an indicator of inflammation, specifically neutrophil recruitment and accumulation. Lower levels of myeloperoxidase activity have been identified In ileal tissue samples

<p dir="rtl">5 Or cecum of the control group treated with Bacteroidetes T/sodium sulfate dextrin compared with sodium sulphate dextrin alone indicates a reduction in neutrophil recruitment and thus a reduction in inflammation, as shown in Table 1 and Table 2.</p>

Table 1:

<tr><td><p>p &gt; 0.05</p></td><td><p>*</p></td><td><p dir="rtl">Standard sample versus strain BT2013</p></td></tr><tr><td><p>p &gt; 0.05</p></td><td><p>*</p></td><td><p dir="rtl">Standard sample versus strain BTE1</p></td></tr><tr><td><p>p &gt; 0.01</p></td><td><p>**</p></td><td><p dir="rtl">Standard sample versus strain BTE2</p></td></tr><tr><td><p>p &gt; 0.001</p></td><td><p>***</p></td><td><p dir="rtl">Standard sample versus dext arn sodium sulphate</p></td></tr><tr><td><p>p &gt; 0.05</p></td><td><p>ns</p></td><td><p dir="rtl">Strain BT2013 vs. strain BTE1</p></td></tr><tr><td><p>p &gt; 0.05</p></td><td><p>ns</p></td><td><p dir="rtl">Strain BT2013 vs. strain BTE2</p></td></tr><tr><td><p>p &gt; 0.001</p></td><td><p>***</p></td><td><p dir="rtl">Strain BT2013 vs. Dextrin Sodium Sulfate</p></td></tr><tr><td><p>p &gt; 0.05</p></td><td><p>ns</p></td><td><p dir="rtl">Strain BTE1 vs. strain BTE2</p></td></tr><tr><td><p>p &gt; 0.001</p></td><td><p>***</p></td><td><p dir="rtl">Strain BTE1 vs. dext arn sodium sulfate</p></td></tr><tr><td><p>p &gt; 0.001</p></td><td><p>***</p></td><td><p dir="rtl">Strain BTE2 vs. Dext Earn Sodium Sulfate</p></td></tr>

Table 2

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<tr><td><p>p &gt; 0.01</p></td><td><p>**</p></td><td><p dir="rtl">Standard sample versus strain BT2013</p></td></tr><tr><td><p>p &gt; 0.05</p></td><td><p>*</p></td><td><p dir="rtl">Standard sample versus strain BTE1</p></td></tr><tr><td><p>p &gt; 0.05</p></td><td><p>*</p></td><td><p dir="rtl">Standard sample versus strain BTE2</p></td></tr><tr><td><p>p &gt; 0.001</p></td><td><p>***</p></td><td><p dir="rtl">Standard sample versus dext arn sodium sulphate</p></td></tr><tr><td><p>p &gt; 0.05</p></td><td><p>Ns</p></td><td><p dir="rtl">Strain BT2013 vs. strain BTE1</p></td></tr><tr><td><p>p &gt; 0.05</p></td><td><p>Ns</p></td><td><p dir="rtl">Strain BT2013 vs. strain BTE2</p></td></tr><tr><td><p>p &gt; 0.01</p></td><td><p>**</p></td><td><p dir="rtl">Strain BT2013 vs. dext arn sodium sulfate</p></td></tr><tr><td><p>p &gt; 0.05</p></td><td><p>Ns</p></td><td><p dir="rtl">Strain BTE1 vs. strain BTE2</p></td></tr><tr><td><p>p &gt; 0.01</p></td><td><p>**</p></td><td><p dir="rtl">Strain BTE1 vs. dext arn sodium sulfate</p></td></tr><tr><td><p>p &gt; 0.01</p></td><td><p>**</p></td><td><p dir="rtl">Strain BTE2 vs. Dext Earn Sodium Sulfate</p></td></tr>

Tissue analysis of the ascending colon was performed (Figures 4 and 5 and Table 3). Histopathology grading scheme was based on the criteria of Berg et al. 1996, as summarized below:

Zero = shallow crypts, no or little infiltrate of inflamed cells, intact epithelium, goblet cells show complete mucin i.e. no EM.

5 1= Crypts may show slight hyperplasia of epithelial cells, some inflammatory cells may be seen

Diffuse infiltrates between crypts, luminal epithelium appears intact, goblet cells may appear slightly mucin depleted.

2= ​​The crypts appear deeper with characteristic evidence of epithelial hyperplasia, mucin depletion of goblet cells, evident infiltrating inflammatory cells and

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It may be multifocal in nature, although infiltrates are not visible in the submucosal layer.

<p dir="rtl">3=Lesions involved a larger area of ​​mucosa and/or were more frequent than seen in grade 2. Lesions did not involve the submucosal layer.</p>

<p dir="rtl">5 Luminal epithelial cells showed small erosions. Lesions are not complete wall.</p>

<p dir="rtl">4= The crypt epithelium appears eroded. There may be abnormalities present.</p>

The epithelial cells appear irregular, sometimes with complete loss.

Incomplete wall infiltration was observed - this was often accompanied by complete loss of epithelial cells to the lumen.

<p dir="rtl">10 Colon rupture as a result of colitis induced by sodium sulfate-induced ERN was significantly reduced when class ERN was treated with strains E1, E2, and BT2013 of Bacteroidetes bacterium. The expression of genes associated with inflammation in the ascending colon was reduced in species colonized with Bacteroidetes compared to those treated with Dext Arne sodium sulfate alone. E1 and BT2013 strains significantly reduced expression of the inflammatory genes IL1B and</p>

<p dir="rtl">15 IL6 compared to strain E2 (Figure 6).</p>

Table No. 3

<tr><td><p dir="rtl">BT strain</p><p>E2</p></td><td><p dir="rtl">BT strain</p><p dir="rtl">2013</p></td><td><p dir="rtl">BT strain</p><p>E1</p></td><td><p dir="rtl">Standard sample</p></td><td><p dir="rtl">the test</p></td></tr><tr><td><p>0.089</p></td><td><p>0.041</p></td><td><p>0.032</p></td><td><p>0.000</p></td><td><p dir="rtl">Dext arn sodium sulfate</p></td></tr>

Model in the laboratory:

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Expression of the inflammatory gene interleukin-8 was altered in intestinal epithelial cells after mono-methylpropylene glycol (PMA acetate) exposure in the presence of Bacteroidetes strains E1, E2, and BT2013 (Figure 7).

Determination of the genome sequence of strain BT2013

<p dir="rtl">5 A deoxygenated RNA sample from strain BT2013 was subjected to sequencing on a MiSeq Nano 2×250 base pair (v2) using the Nextera XT library for rapid fragmentation and labeling with sequencing adapters, giving a total of 4,605,120 reads (1,115,615,927 bases).</p>

Data analysis summarized below:

<p dir="rtl">10 Map the sequence to the reference sequence (004663_NC and 004703_NC) using bowtie2 (2.2.2).</p>

Calling insertions or deletions (InDel) of single nucleotide variants (SNVs) and small nucleotides using VarScan (2.3.7) and SNVer (0.5.3) consensus calling function to avoid false positives.

<p dir="rtl">15 C. Variant footer using gff reference.</p>

<p dir="rtl">Dr.. Calling large InDel insertions or deletions using pindel (0.2.5a3).</p>

<p dir="rtl">H. Assembling desequenced reads using SOAPdenovo (2.04)</p>

<p dir="rtl">And the. Release of the combined sequences against the National Center for Biotechnology Information's nucleotide database</p>

20 g. Sub-titrate all sample readings to 50%

<p dir="rtl">H. Compile back the sub-calibrated readings using SOAPdenovo (2.04)</p>

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Sequences were mapped to the reference sequence (004663_NC and 004703_NC) using bowtie2 (2.2.2). Nucleotide variants, small insertions and/or deletions were identified using VarScan (2.3.7) and SNVer (0.5.3) to avoid false positives during mapping The sequence and variants were annotated using the identified reference sequence

5 and large deletions using pindel (0.2.5a3). Unsequenced reads were reassembled using SOAPdenovo (2.04). Sequence fragments were reassembled into contigs and launched against the NCBI nucleotide database. Subcalibration was performed All reads were sampled to 50% and then reassembled using SOAPdenovo (2.04) to give a of novo sequence assembly of the strain.

.BT2013 10

Sequences: SEQ ID NO: 1 (sequenced version of of novo sequence assembly for strain BT2013) - see electronic sequence list.

Sequences:

SEQ ID NO:1 (concatenated version of the of novo sequence assembly of BT2013) – see electronic sequence listing. 15

SEQUENCE LISTING

&lt;110&gt; 4D Pharma Research Ltd

&lt;120&gt; Immune modulation

&lt;130&gt; P067636WO

&lt;150&gt; GB 1423084.1 20

&lt;151&gt; 2014-12-23

&lt;160&gt; 1

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&lt;210&gt; 1

&lt;211&gt; 6574984

&lt;212&gt; DNA

&lt;213&gt; Bacteroides thetaiotaomicron

&lt;400&gt; 1 5

aaaaaaaaag ggtccaattt gatttatttt ggtcccggtg tgcataatct tcctaatgat 60

actctatttg tcccctcagg aactactgtt tatatcgatg ggggagctcg tgtttatggc 120

aatatattaa aataagtaaa ccggaggcag gaataataaa taataaagta aacagctgcc

180

agggttagta atatttctag tcaacacata gcagctatta gagataaaca agtcaaccat 240 10

tattagggaa gtacatacat atgccatcgg attaatctga tgcaaagcta caaattcaag 300

tccgttcgct cggaaaatcg ctgtaactaa ctaaatttca aatatttcaa agaactcttt 360

tagattttaa tgggacagca atgaaccaac aaaagacaac taacatagga ataagaataa

420

caaaagtaaa cctatttaga tattaaagta tattgagtaa actaattcag ttataacaaa 480 15

cgaagttgtc aactaaaacc agtacacatc ataccaacaa aagacaacta acataggaat

540

aagaataaca aaagtaaacc tatttagata ttaaagtata ttgagtaaac taattcagtt 600

ataacaaacg aagttgtcaa ctaaaaccag tacacatcag attattaaag aatttcggtt 660

atcgatgggg atgcgttcca ttaggcagtt ggtgaggtaa cggctcacca aaccttcgat 720 20

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ggataggggt tctgagagga aggtccccca cattggaact gagacacgat ggagtgcata

780

caagagccag tccattccag gatatattac ctttaagaat ggactggata gattttatac 840

acagtttgaa ctgtatgagt taatcagcta agacttgtgt ataaagggta gcttccagag 900

agttgcagtc tgattcagcc tatagtcatt taagactagt gtcaaagtta gttcactgca 960 5

actctacttt tcaaatatac acttatattt tgttgtgata tttaatactg caaatgtaaa 1020

tgtgaggagg ggatcttgtt taacgaacgg ctgtatcaaa caccgattcg aaaggacgtt 1080

tgggacgcag ataagaaacg cattccggca cgtaacatga ttatcgtcgc atcgacgggt

1140

gggggaaagt cgcaacggaa cccagtacga aagaaaccag caggaagaac ccaagcacaa 10

1200

cggaacccag tacgaaagaa accagcagga agaacccaag cacaacggaa cccagtacga

1260

aagaaaccag caggaagaac ctgataagac tcatctgaga gacctctttg ataaaactaa

1320 15

atttcaaaat gacaaagaac gattcggacc aaatggggcca agtttattta atttttaatt 1380

cgtcccaatt ttaatggggac actaatgact gtagtgtact gaataagttg acacttcaaa 1440

aatcgaaaat aaagatgaaa tattcgaaaa agaagtacaa ctattacagt gatgatgaac

1500

gaatgtctta tattcgtgag tatttatcaa gtcccgcgac cctcaaaaga gggcttcgat 1560 20

8068

-38-

attgtcattg gcaatccacc gtacggagcg aaatacgaca accaaacaaa gaggtattat

1620

aagaatacct atgtgacggc aaatagcatc cgaggattac agaacgcgtc ctcgcaatct

1680

ctcagtagag gtcaatggag atatttttca caatcttcat ctttttgcga atccgattga 1740 5

taaatttcgt ccttccgata aagaaatcca aagggctctc aagaaaaaaa aatctgtagt 1800

gtactgaata agttgacact tcaaaaatcg aaaataaaga tgaaatattc gaaaaagaag

1860

tacaactatt acagtgatga tgaacgaatg tcttatattc gtgagtattt atcaagtccc 1920

ttaaagtatg aacgcttaca agaattgtct gcttacggtg acagatttgt tttcataaaa 1980 10

gacagtattg ctaaaaagga aattgttgag tctattttca ctaactacca tcctcaggta 2040

gtcgtgaatg cccgtgagcg attcgccact acgcagttga gataacgctt tgtcacgcat 2100

ctgctgatac tcttcactgt ttctatccat aatacaaaga taattgtttg gggacagagt 2160

tcagattacg ccctcctgtc gctgcggaac gtagagtaat tgatccccat gcagagcgac 2220

gaatgcagat ccgaaagaaa caggtagtcc ggattcaggt tgttttcccg gccgatgatc 2280 15

gagcctataa agatattata aagcaacggg gaattacaga accgttacta cccaagacgt

2340

taccaaagcg ggtagtgata aatttggtat ggccttttac ttttccctca cggatagcac 2400

atcccagact ctgtacatag atttcggcca atcacacaca cacacacaca cacacacaca

2460 20

8068

-39-

cacgagtgtg tgtagaaacc tatatttaag acttttcaag gtaattctcc tttctttttt 2520

atcgtgttcc gttcttttcg tttccgctca agagacacgg gaagccaaga gcaaaattct 2580

tgaccttgcc atacatggta agctagtacc acaagatccc aatgaagagc cagcaattaa

2640

gctgttgaag cgtataaatc ccgacttcac accttgtgat aacggggcatt aagtgtctta 2700 5

ccctggattt ggttgactac tataagtatc aactaaaatg aataaaagat gaaaaagagt 2760

gacatgacct ttagtcctta tcagcttgaa cttcttggcg atttctatcg ttcgaatttc 2820

cgggacttga taaatactca cgaatataag acattcgttc atcatcactg taatagtttgt 2880

acttcttttt cgaatatttc atctttattt tcgatttttg aagtgtcaac ttattcagta 2940

cactacaaag tttttggtta gttgctcttt ctggggtagc agatatttta tagtaagtta 3000 10

tatgcaaaaa aaacagaaaa aagttggaaa tattgatttt ttttataaac acacacacac 3060

acacacacac acacacacaa ctctcgttgg gaccctttat cccgaagtta cagggtcaat 3120

ttgcctagtt ccttaaccgt gaatcactca agcgccttag tatattcaac ccgactacgt 3180

gtgtccgttt gcggtacggg taccttaaag actgatgtgt actggtttta gttgacaact 3240

tcgtttgtta taactgaatt agtttactca atatacttta atatctaaat aggtttactt 3300 15

ttgttattct tattcctatg ttagttgtct tttgttggcc gttttcgtca gcctcactga 3360

tactcggagc aatcaacgtt ttcaatccac tccttttaca atactgaagc aggcggtctt 3420

cctcttcacg ggtattctcg taacgggcaa acaggatgcc gccgatacat gacttttgac 3480

acatttacat ttgcagtatt aaatatcaca acaaaatata agtgtatatt tgaaaagtag 3540

8068

-40-

agttgcagtg aactaacttt gacactagtc ttaaatgact ataggctgaa tcagactgca 3600

atgctgcaca actatcgtaa caatccctgt gtagtgatgt ggagtatcgg taatgaagtc 3660

cccacgcaat gcagccctgt aggatataaa gtagccaagt tcctgcaaga tatctgccac

3720

cgtgaagacc ctccctaccc gccccgttac ctgcggcatg gaccaagtga cttgtgttct 3780 5

agccaacgga tttgctgcca tgatcgatat ccccggtctg aactaccgcg ccaatcgcta 3840

tcaggaggca tatgacaaac ttccccggat ctgcgtgcca cggatattcc ggataatgga 3900

aactgcactc tccaccgatt ccagaaactc ggccagcctg tcccggtctg ccttcgccag 3960

tttctcgcta tacgccaacg ggttggcctg gtacgctttt gacacattta catttgcagt 4020

attaaatatc acaacaaaat ataagtgtat atttgaaaag tagagttgca gtgaactaac 4080 10

tttgacacta gtcttaaatg actataggct gaatcagact gcaactctcg ctcagtgaaa 4140

ttgtagtatc ggtgaagatg ccgattaccc gcgatgggac gaaaagaccc cgtgaacctt

4200

tactatagct taacattgaa tttgggtaat tgatgtgtag gataggccgg agactttgaa 4260

gcaagagtgt gaattctaag tcctctccaa acaatatcta taaaatctta cccaagttta 4320 15

cgaacattaa cgtatccttg ggtaagtttg tatatagaca tacctactct tcagaagtgt 4380

atagctactt cctaaaacaa gagaaagaaa gaagccgagt ctaacatcag gtagacaagg

4440

ttgaactagt cctatagctc agttggttag agcgctacac tgataatgta gaggtcggca 4500

gttcaactct gcctgggact actccgaaca tattcaaatg caatttaagc ccgggtaagg 4560 20

8068

-41-

ttcctcgcgt atcatcgaat taaaccacat gttcctccgc ttgtgcgggc ccccgtcaat 4620

tcctttgagt ttcaccgttg ccggcgtact ccccaggtgg aatacacgac atcgctccag 4680

aaaggaggtg ttccagccgc accttccggt acggctacct tgttacgact tagccccaat 4740

taccagtttt accctaggac gctccttgcg gttacgtact tcaggtaccc ccggctttca 4800

tagtccaaag cctcggtagg ccaataacga aggtcgctcg cattgtcata atccccactta 4860 5

ccatttttgt acacgatctt cactccgtca tgttcaaatt ccgtgtcgtt ctttcccatg 4920

aaggcagtac catccgccct ggaacacttc accctcccgt gaaaaggaat gcaccccctt

4980

ccttacctgg tgcgtgtaac cttgttccct catggctgcg acgatctggt ttgccgccgt 5040

aaactgctcg tcctgcaata tccttttaag ctcctgcaaa ccgttctccc tgtacccggc 5100 10

cgggttcgcc tcgtactttg tcaagtcgaa acgttccgtt atgcttttta gctgctcgtc 5160

agacagaggt tgttcgaacg ctttcaagag cctgtgttca acctggaacc cgttttccca 5220

tatccgggcg tttcacctgc gaacgtcacc gtcccactgg ctgcggcgtg tacggtagcc 5280

gcatacaccg ccgccatatc caggcctgcg tgaaactgcc tttcaccgct tatcggatgc 5340

gtccggatac gaagtcaaat taagcgtagt ggtatcctga gtagcgcggg acacgagaaaa 15

5400

tcttgcgtga atctgccggg accatccggt aaggctaaat actcccgaga gaccgatagc

5460

gaaccagtac tgtgaaggaa aggtgaggat attgcaggac gagcagttta cggcggcaaa

5520 20

8068

-42-

ccagatcgtc gcagccatga gggaacaagg ttacacgcac caggtaagga agggggtgca

5580

ttccttttca cgggaggtg aagtgttcca ggttgaacac aggcccacca gacggtggaa

5640

acgttcgggg tggtgataac gacggtacac aacatcaaag gcacaaaccg ggtagccctg 5

5700

acgctcaacc cctgggcgat ccctttcctg ctctactacg gtacgggtgt cggcggtaca 5760

aggtatatcc tttacctgca aaccgttctc cctgtacccg gccgggttcg cctcgtactt 5820

tgtcaagtcg aaacgttccg ttatgctttt tagctgctcg tcagacagag gttgttcgaa 5880

cgctttcaag agcctgtgtt catccgcagc gaca aggagg ggatcttgtt taacgaacgg 5940 10

ctgtatcaaa caccgattcg aaaggacgtt tgggacgcag ataagaaacg cattccggca

6000

cgtaacatga ttatcgtcgc atcgacgggt gggggaaagt caggcaactg cgtataatgc

6060

ccgttatcac aaggtgtgaa gtcgggattt atacgcttca acagcttaat tgctggctct 6120 15

tcattgggat cttgtggtac tagcttacca tgtatggcaa ggtcaagaat tttgctcttg 6180

gctgaatgcc gtgttctcaa agtattataa tgataaggcc tattttgatg cggtgcagaa 6240

cggggcggtc tataaatgcg agatagacag catccagacg atcgccgggg acaatgagcc

6300

gtacaaggtg gctttcactt cctgtataaa ctggttaaag aaaaatcccg tcacgttctc 6360 20

cggaaattgc ggcgtggttc tcacgatctc ccctttcgtc ctgataagaa accttagctt 6420

8068

-43-

ctgccccgaa acgccgtaaa tcgtcagggt ggaagtgaaa gccaaagaaa aatcccgtca

6480

cgttctccgg aaattgcggc gtggttctca cgatctcccc tttcgtcctg ataagaaacc 6540

ttagcttctg ccccgaaacg ccgtaaatcg tcagggtgga agtgaaagcc accttgtacg 6600

gctcattatc gtcgcatcga cgggtggggg aaagtcggtt acgtcgttga acatcatcca 6660 5

gcagaacatc gagcagaatt ataaacagat cgtcgtcgag ttcggaaaga gcttttacca

6720

gctttcgcag ttgtacccgg acaggtcgct gccaactgga acaggaagcc agggaaaacc

6780

gggagaaggc cgggaaactg caaacggatc tcgaaatagc ccggcaggag aaaggaactc 10

6840

cggccgtcgg atgcaatacg cacaagatcc tggagatcgt ggagcgtatc gacgagggga

6900

gcgtatcgac gaggtgaaga agataccgac attcaacgat acggtttatg agatagaccg

6960 15

taatacgctg gatatgtggg tgaaaaggtt aaaggacgaa ctaaagagat aagcctatgt

7020

ttgccaaagt acacccggcc gatgcagaag cgtttcgtaa aagctctgca tatcgacgaa

7080

ctgcgagcga agcggcacta cgatataatc ggctaaagga gaatagaaag ccctgtcgcc 20

7140

8068

-44-

ttgctgctcc cgtatcgggc aaaaccagct tttcgcctcc agcatggctt aacctggatc 7200

agaccaattt ttcggacgtg aggccggaag aatgggaagc gttaagggag aagttcagag

7260

ggggacaggc agagcagccc gacgggacaa ccggagaggc gcaccccgaa atagatgcca 7320 5

tgctggaggc gaaaaaaaca actgcctaaa gacctcttta accagcctgt cgtcgagatc

7380

aaatgcgacg aagccggggg gaagaacaac aagagcaaag ttctgaaaga ggctatcgcc

7440

atgatgcgga aaaacttttc ctttcgctgg gtgcatccca ataactttgc cacggtgcgg 7500 10

gtagtattcg actggaccaa gatttccaat catgacaagc ctgaaggcat gagggtcgta 7560

ttttatccga ccgatgatga aagcaacacg tggatatttg atttccccgg aggagaggat 7620

ggggaagtgg agctgtctgg ttatccggcg accgaacatc acgcgtatcg gcagtaaaaa

7680

gcgtgtaact gccgttttct ttccaaacca tcccgtcggt atcgtagttg aagcaaatta 7740 15

cccggtaatc attctcgggg agctccactt ccccatcctc tccgctggtt ttgcccgata 7800

cgggagcagc aaggcgacag ggctttctat tctcctttag ccgattatat cgtagtgccg 7860

cttcgctcgc agttcgtcga tatgcagagc ttttacgaaa cgcttctgca tgaaatggga 7920

cattccacgg gacatgacaa tgggcaagca cgtatactgc cagaaaccgt tgactcactc 7980 20

cgtttacgaa tcccgtttgc tgaccaagct ggccgcctct accggagtag ttactcaaat 8040

8068

-45-

gggtaatcag ggagcatcgg gcgaaggtac cgacctggtt tgcgccgagg ccgtcagtgc

8100

gttaagcgtg agcagcgaca gcgagggagg acagtcgatc aggatataat cgaatttctc

8160

cttttggcct ttgataaggt gggctaagat aagctcccgt ccggcctcgt tgattaactc 8220 5

cgtttcaacg gccgagcgct taacgcactg acggcctcgg atcggttgat tatcccggtt 8280

caggctcaat tcctggcaat gcgtggaatg gccaaactta tgcaggtagt ccacaaggtg

8340

cagcaacgtt tgaactcgga tctttcgatc gccggggttc tgataaccta ttaccgaata 8400

ctatgacgta cgtttaaagt atgaacgctt acaagaattg tctgcttacg gtgacagatt 8460 10

tgttttcata aaagacagta ttgctaaaaa ggaaattgtt gagtctattt tcactaacta 8520

ccatcctcag gtagtcgtga aaacttatgt acgtccgcag gtatcggccg agatcgggaa 8580

gatcacgaac ccggagctta aaaggatatt gcaggacgag cagtttacgg cggcaaacca

8640

gatcgtcgca gccatgagggg aacaaggtta cacgcaccag gtaaggaagg gggtacacgc 15

8700

accaggtaag gaagggggtg cattcctttt cacgggaggg tgaagtgttc caggttgaac 8760

acaggctctt gaaagcgttc gaacaacctc tgtctgacga gcagctaaaa agcataacgg

8820

aacgtttcga cttgacaaag tacgaggcat tccttttcac ggggagggtga agtgttccag 8880 20

8068

-46-

gttgaacaca ggctcttgaa agcgttcgaa caacctctgt ctgacgagca gctaaaaagc

8940

ataacggaac gtttcgactt gacaaagtac gaggcgaacc cggccgggta caggggagaac

9000

cttcaccctc ccgtgaaaag gaatgcaccc ccttccttac ctggtgcgtg taaccttgtt 9060 5

ccctcatggc tgcgacgatc tggtttgccg ccgtaaactg ctcgtcctgc aatatccttt 9120

taagctccgg gttcgtgatc ttcccgatct cggcacaaga gaaagaaaga agccgagtct

9180

aacatcaggt agacaaggtt gaactagtcc tatagctcag ttggttagag cgctacactg 9240

ataatgtaga ggtcggcagt tcaactctgc ctgggactac ttcgagaaag aaaatgaaaa 10

9300

cggcagtgat gtacaagccg actttggcgg ccgtacctac ccggccgatc cgcatcgccg

9360

gaagcgacgg ggacgaaacg gaagaaccgg aagatccgga cgagggggag agcaaaagcg 9420 15

gaaagcggaa gaaatacacc tgtgggtgcg gctgtaacgt gtggggaaat tctggatgct

9480

cacaatagtg atatccggat tattgccaag attgagaatc aggaaggggt ggacaacatc

9540

gacgagattc ttgaagtggc ggacggcgtg atggtagccc gtggtgacct gggtatcgaa 20

9600

8068

-47-

gtgccgcagg aacgtattcc gggactttat agtgggagct gttcattagc cggactttca 9660

atgccacact ctttatcatca ataccataga tcagaatatg catattcttc ttattcagca 9720

tattcagcag gagttcataa accagaatca actgaatacg gaagcctacc atggcaataa

9780

atcgaagtgc cgcaggaacg tattccgggt atccagcgtg tgctgatccg caaatgtatc 9840 5

ctggcaaaga aaccggtgat cgttgcgact cagatgcttc ataccatgat caacaatcct 9900

cgtccgaccc gcgcggaagt gaccgatatc gcgaatgcca ttttagagtt tttgataacc 9960

ccgttcacct gccggtacag atccaggctc ttagtcagta tgtccctgga ttcccccagc 10020

acttgaaact gttcgtatgc ctgtttaagt tctttcgccc aggttatctg cgatagctgc 10080

gtcaaggccg gatcctccat gatcttgttc agcacgttcg tatattcccc gtatgcctcc 10140 10

tgtccggtaa acacgtccga ccgggtgcac tctttcgccg ccagttccaa catttcccccc 10200

tgcatggaaa gcacctgcaa caccatttta gagtttttga taacccccgtt cacagacggc 10260

agataactgt tgcttaagaa gagaaggggg aagaacatcg agaagagaca gagaacgggt

10320

caaaacagcc tgttttcttt cttcgtcttc cggattggcg tacatcgaca cattatatcc 10380 15

ctgaaggatg gccaaacaca gggtagcatc ctggaccctg agcttcatgg acaagttcgc

10440

ggatcgtgtt cagtttaccg ctgagctggt agataccggg acgatagaca gcgccacgga

10500

tttccagttt gtttgtgaag cggttaagga tggcttcggc tgttacaacg tcaccgttac 10560 20

8068

-48-

gcattgtgta gatgccaaac tcgatcgcct ttcccgtcgt gcttaacgtc accttttcga 10620

cggccagttc ttcatcgctt agaatcaccg ggcttgcgag gctttccccc gtcgccccgt 10680

ctttcaactg cgtaccgttg gcgactacca cgaccgactt aatgaagctg cggaaatcag

10740

ctctgcatat cgacgaactg cgagcgaagc ggcactacga tataatcggc taaaggagaa 5

10800

tagaaagccc tgtcgccttg ctgctcccgt atcgggcaaa accagctttt cgcctccagc 10860

atggcatcta tttcggggtg cgcctctccg gttgtcccgt cctccttccc gtccccggaaa 10920

acaaggctct ttttctcgat ctcctttccg tttttgtaaa cggtcactac ccactgcatc 10980

ggctcgttca caacgccgtc ctctccgtcc acgacaccac cggaaacggc aaactcgatc 10

11040

gcctttcccg tcgtgcttaa cgtcaaccgg gtagccctga cgctcaaccc ctgggcgatc

11100

cctttcctgc tctactacgg tacgggtgtc ggcggtacaa ggtacgggaa gaacatcgcc

11160 15

ttaaccctcc ggggcaatta caccaagcgg ctctacaaga tcatttgcag ccaacgggac

11220

agacgggaga gagtgtaatg gcataagggc gcttgactgg gagacttaca agtcgatcag

11280

gtaggaaact agagcatagt gatccggtgt ttccgtatgg aagggacatc gctcaaagga 20

11340

8068

-49-

taaaaggtac tccggggata acaggctgat ccctcccaag agctcatatc gacgagcatc

11400

taagtacgaa gccagccaca agattagatt tcttagggtc gttaaagacg atgacgttga

11460

taggatgcag gtgtaaaggt ggtaacatca aagccgagca ttactaattg cccgttcact 5

11520

ttctttcgga cggtgcggat cgcgatatat acgtttagcc tacaagatca tttgcagcca 11580

acgggacaga cgggagtatt attactcgat cgaccaattc tgcaaagacc tggagatccc

11640

ggcctcctac tcgaatgcac agatcgacca aaaggtttta aggcctgcac agacacgaat 10

11700

caaggaaagc gaggccgatg tatgctccgc accgctttac gtaagacaaa ttcatccggt

11760

ttacctccgt acgctctttc agttcaaagc ctttcagata aatctgcgta gtcttgatgg 11820

acttatgacc aagcgactcg ctgatcatct cgatagggac accacggtac ttggcagtag 15

11880

tagcccacgg aaacgccgaa gaaggaagag cctgaaagga cagtaggacg tttcttttcg

11940

ggggaagaac cggagaacaa gggaaacacg atagaggcca ttgtgtcggg cgatcagaag

12000 20

atcacgaacg ggagcgtgat aaaacttgtc acgctccaag aaatgcaact gcccgtgctt

12060

8068

-50-

ctgcattttc gaaattccat tctccatcat cggttaagta agtttgaaag aaagtaagca 12120

agggcgcatg gcggatgcct tggctctcgg aggcgatgaa ggacgtgata agctgcgata 12180

agctctgggt aggtgcaaat aacctttgat ccagagattt ccatctccag gtctttgcag 12240

aattggtcga tcgagtaata atactcccgt ctgtcccgtt ggctgcaaat gatcttgtag 12300 5

agccgcttgg tgtaattgcc ccggagggtt aaggcgatgt tcttcccgta ccttgtaccg 12360

ccgacacccg taccgtagta gagcaggaaa atctccaggt ctttgcagaa ttggtcgatc

12420

gagtaataat actcccgtct gtcccgttgg ctgcaaatga tcttgtagag ccgcttggtg 12480

taattgcccc ggagggttaa ggcgatgttc ttcccgtccc ttgtaccgcc gacacccgta 12540 10

ccgtagtaga gcaggaaaat ctccaggtct ttgcagaatt ggtcgatcga gtaataatcc

12600

tcccgtctgt cccgttggct gcaaatgatc ttgtagagcc gcttggtgta attgccccgg 12660

agggttaagg cgatgttctt cccgtacctt gtaccgccga cacccgtacc gtagtagagc 12720 15

aggaaaatct ccaggtcttt gcagaattgg tcgatcgagt aataatcctc ccgtctgtcc 12780

cgttggctgc aaatgatctt gtagagccgc ttggtgtaat tgccccggag ggttaaggcg 12840

atgttcttcc cgtcccttgt accgccgaca cccgtaccgt agtagagcag gaaaagcctc

12900

cgaaacgttc aattagtacg caacggaaag aatatcgcca ccatcgacgt ctacgaattt 20

12960

8068

-51-

atcatgaaag gcaacacaca ggatgacatc cgccttcagg aaggtgacgt cgtgattgtt

13020

cccgcttatg atgtattggt aaagatcagc ggcaaggtaa aaccagggac atactgacta

13080

agagcctgga tctgtaccgg caggtgaacg gggttatcaa aaactctaaa atggtgttgc 5

13140

aggtgctttc catgcagggg gaaatgttgg aactggcggc gaaagagtgc acccggtcgg

13200

acgtgtttac cggacacggag gcatacgggg aaaaatctca ttgccttcac ccatcgtagc

13260 10

agcttccatt accaggcgac aagcttcggg gatagtcata aagaaacgaa tgatatcggg

13320

gtgagtcact gtgacaggac cgccattctc aatctgttcc ttaaaacggg gaattacaga

13380

accgttacta cccaagacgt taccaccacc ccgaaaacgg ccgtcccctt gttaatcacc 15

13440

atgccgccgg gcagttgcat ttcttggagc gtgacaagtt ttatcacgct cccgttcgtg 13500

atcttctgat cgcccgacac aatggcctct atcgtgtttc ccttgttctc cggttcttcc 13560

cccgaaaaga aacgaacgga acccagtacg aaagaaacca gcaggaagaa

cccaagcaca 13620 20

acggaaccca gtacgaaaga aaccagcagg aagaacccaa gcacaacgga acccagtacg

13680

8068

-52-

aaagaaacca gcaggaagaa cccaagcaca acggaaccca gtacgaaaga aaccagcagg 13740

aagaaaggaa cagttaaggc agaaccagag agccgacagt ctgaaagcgg ccgcagccat

13800

gaaacggaga acggcgaaag cccggccgaa aaaggaaacg ccgaagaagg 5 aagagcctga 13860

aaggacagta ggacgtttct tttcggggga agaaccggag aacaagggaa acacgataac

13920

cccctggatg ctccagaatc tcacccccgc cggaacattc ttcctgttcg cagtcatgtg 13980

cgtgccgtat atgctcatcg tatggaaact cgtgccggag accacaggaa agtcactgga 10

14040

agagattgaa agatactgga cccggtcgga acagtagaag aaagaaaaga ggccattgtg

14100

tcgggcgatc agaagatcac gaacgggagc gtgataaaac ttgtcacgct ccaagaaatg 14160 15

caactgcccg gcggcatggt gattaacaag gggacggccg ttttcggggt ggtgaagctc

14220

gcacaggaca ggatcaatat aacggttgaa tccgtccggc gctcccgttc gtgatcttct 14280

gatcgcccga cacaatggcc tctatcgtgt ttcccttgtt ctccggttct tcccccgaaa 14340

agaaacgtcc tactgtcctt tcaggctctt ccttcttcgg cgtttccttt ttcggccggg 14400 20

ctttcgccgt tctccgtttc atggctgcgg cccattgacc aatattcctc actgctgcct 14460

8068

-53-

cccgtaggag tttggaccgt gtctcagttc caatgtgggg gaccttcctc tcagaacccc 14520

tatccatcga aggtttggtg agccgttacc tcaccaactg cctaatggaa cgcatcccca

14580

tcgataaccg aaattcttta ataacccttc cattttcgaa aacgcaggac tttcaggagg 14640

agattctttg ttttaccaag ttctcgtagg actagtcaac actctgacca ccgttctttgc 14700 5

tcttgtgatc attgacaggg tcggccgcaa gaaactggtc tattacggag tttcggggtat 14760

ggttgtctcc ctcctgcccc ttccattttc gaaaacgcag gactttcagg aggagattct 14820

ttgttttacc aagttctcgt aggactagtc aacactctga ccaccgttct tgctcttgtg 14880

atcattgaca gggtcggccg caagcaactg gtctattacg gagtttcggg gatggttgtc 14940

tccctcctgc gattttctct gcatatattt aacagtcaaa gcgacaaact tgcgtttttt 15000 10

accaagttct cgtaggacta gtcaacactc tgacccaccgt tcttgctctt gtgatcattg 15060

acagggtcgg ccgcaagaaa ctggtctatt acggagtttc gggtatggtt gtctccctcc 15120

tgcgattttc tctgcatata tttaacagtc aaagcgacaa acttgcgttt tttaccaagt 15180

tctcgtagga ctagtcaaca ctctgaccac cgttcttgct cttgtgatca ttgacagggt 15240

cggccgcaag caactggtct attacggagt ttcggggatg gttgtctccc tcctgcaaat 15300 15

attaattttg ctgacacagt ttaattgaat tctctttttg ctgttcattt gctttatttc 15360

aggacttcgc ccttctcgtt gaagaacact tcgctgtccg tgccttctgc atcggtaaat 15420

gtcaccttgt aggtctttgt gccttcctcg ctttcctcaa ctgcggcttc ctgccgcttg 15480

gtgtaattgc cccggagggt taaggcgatg ttcttcccgt accttgtacc gccgacaccc 15540

8068

-54-

gtaccgtagt agagcaggaa agggatcgcc caggggttga gcgtcaggggc tacccggttt

15600

gtgcctttga tgttgtgtac cgtcgttatc accaccccga acgtttccaa gtaagtttga 15660

aagaaagtaa gcaagggcgc atggcggatg ccttggctct cggaggcgat gaaggacgtg 15720 5

ataagctgcg ataagctctg ggtaggtgca aataaccttt gatccagaga tttccgaatg 15780

ggacaacccg gcattctgaa ggaatgtcat ccatctttga tggaacggga agaacatcgc

15840

cttaaccctc cggggcaatt acaccaagcg gctctacaag atcatttgca gccaacggga 15900 10

cagacgggag tattattact cgatcgacca attctgcaaa gacctggaga tcccggcctc

15960

ctactcgaat gcacagatcg accaaaaggt tttaaggcct cgccggcaac atggtatcgg

16020

atgttgagat tgtggtaatg gtgaacgatt ataagccaat cgaggtaaag gatctgccgc 15

16080

aggcggttca ggacacgatc aagaaggatt tcgcagacct gacaatcaag gaagccgcag

16140

ttgaggaaag cgaggaaggc acaaagacct acaaggagta ccgcttccat actcatccat 16200 20

gcaggtataa cttatctttt ggacatcctt ggtggcttcc caactataaa acgccatcat 16260

8068

-55-

gtcttcacta accgttccgg gattgaacgc gtaaaagtcc aaagcctcgg taggccaata

16320

acgaaggtcg ctcgcattgt cataatccca cttttcctct gatccgaacg ggtgcgcaag 16380

atcccggttc aatcgggtgg ggtgtcccgt ggaatgtccc atttcatgca gaagcgtttc 16440

gtaaaagctc tgcatatcga cgaactgcga gcgaagcggc actacgatat aatcggctaa 5

16500

aggagaatag aaagccctgt cgccttgctg cgtgtcccgc gctactcagg ataccactac

16560

gcttaatttg acttcgtata ccggactatc accgtctatg gttcaacttt ccagaggatt 16620

ctactcatca aatgtcttgc gacatcgtgg tcctacaacc ccacacatgc cgtaacatgg 16680 10

gtggtttggg ctattccccg ttcgctccct cggtaggcca ataacgaagg tcgctcgcat 16740

tgtcataatc ccacttacca tttttgtaca cgatcttcac tccgtcatgt tcaaattccg 16800

tgtcgttctt tcccatgaag gcagtaccat ccgccgtaaa agcgaacacg tcgaaatcgg

16860

tgttcttcaa gttggtgttg gtagaggtac ccgtaccgca aacggacaca cgtagtcggg 15

16920

ttgaatatac taaggcgctt gagtgattca cggttaagga actaggcaaa ttgaccctgt 16980

aacttcggga taaagggtcc caacgagagt tgggcgcaga gaataggtcc aggcaactgt

17040

ttaacaaaaa cacagggctg tgcggttatc ctaccaaggt ggaaggttct tctactttat 17100 20

8068

-56-

tactgagtgc ctgcgctcct caggcccaac acgtgaagat gattttcccc gcccgcgaca

17160

atatgccgaa agttgccttg ccggaagttg aggtacactg gtatgacggc ggtatgatgc

17220

cggaacgtcc gaaaggtttc ccccgttatg ctttttagct gctcgtcaga cagaggtttgt 17280 5

tcgaacgctt tcaagagcct gtgttcaacc tggaacactt caccctcccg tgaaaaggaa

17340

tgcaccccct tccttacctg gtgcgtgtaa ccttgttccc tcatggctgc gacgatctgg 17400

tttgccgccg taaactgctc gtcacctggg cgaaagaact taaacaggca tacgaacagt 17460 10

ttcaagtgct gggggaatcc agggacatac tgactaagag cctggatctg taccggcagg

17520

tgaacggggt tatcaaaaac tctaaaatgg tgttgcaggt gctttccatg cagggggaaa

17580

tgttggaact ggcggcgaaa gagtgcgcgt tacgtcaaaa agggtacaag gttcttttga 15

17640

tcgaccttga cgggcaggcc aacctgaccg aatcgctggg cttctctgcg gagcttcccc

17700

aaacgatcta cggtgcgatg aaaggcgaat acgacctgcc gatctacgag cataaggacg 17760 20

gccttagcgt cgttccctcc tgcctggata tgctcaccga gggcgatatg atcgtccgga 17820

8068

-57-

tcaggtcaaa ggaaagcacg ctttcctcca tgatcttgtt cagcacgttc gtatattccc 17880

cgtatgcctc ctgtccggta aacacgtccg accgggtgca ctctttcgcc gccagttcca 17940

acatttcccc ctgcatggaa agcacctgca acaactattt cctgcccgat atgtcgagca 18000

tacggccgga cactatctat ctgaatgagg tgtcgcaaac gcacctgatc gcaccggaaa 18060 5

aggtgattta tatagattac ggcgatacct gcatacacggt aagcaaggcc gagaataccg

18120

agaatatcgt gcgaatgatc gcagccacgg gaaaggaagc aaggccgaga ataccgagaa

18180

tatcgtgcga atgatcgcag ccacgggaaa ggtggaggaa tttcccaggc agacaaacgt 10

18240

gtcgctggcg accgaagggg ggaagttcta cacgttcaac gtggattatc ggcagcagcc

18300

ggaggcgttc gtctatgaga tagggggagaa acggccggag cctgccgatc tacgagcata 18360 15

aggacggcct tagcgtcgtt ccctcctgcc tggatctctc ggccgttgaa acggagttaa 18420

tcaacgaggc cggacgggag ctttatcttag cccaccttat caaaggccaa aaggagaaat

18480

tcgattatat cctgatcgac tgtcctccct cgctgtcgct gctcccagaa agtagaagaa 18540

cggcactttg ttcgccagcg tgaaacgccg ggacgaaatg gaaagcatga gcgatataac 20

18600

8068

-58-

cggggaaatc aggttttcga tctgataggc gttcgatacg acaaccaatt tcggacattc 18660

cggatctatc aggttaaagt cgaaatcatt tccggaaagg acataacaca tgcgaagaaa

18720

tactgggatt accgcaagat gtacgatgaa atgggcaaat ccattgacgg cgtaatcatt 18780 5

gctaccgccg accatactca tgccatcatc acggcagacg ctatgacaat gggcaaacac

18840

gtatattgcc agaaaccgtt gactcactcc gtttacgaat cccgtttgct gaccaaactg 18900

cctgtttcct gtcgttcaga cgcaggaagg tagcggattg agccttgtcc cggcaacaag 18960 10

tgccgggcag agcgaaaccg caccgggcat tgaaaacgac tgagtacaca ccgcatggggc

19020

tactaccgca taggctgtcg cttgtggtcc ggcttgccgg ggtgtgagcg ggagccggag

19080

ccgaactgcc tgtttcctgt cgttcagacg caggaaggta gcggattgag ccttgtcccg 19140 15

gcaacaagtg ccgggcagag cgaaaccgca ccgggcattg aaaacgactg agtacacacc

19200

gcatggggcta ccatcgcata ggctgtcgct tgtggcccgg attgccggat tgctatcaca 19260

cacctggcag gatcctgcca ggtgtgtgat agcaatccgg caatccgggc cacaagcgac 19320 20

agcctatgcg atggtagccc atgcggtgtg tactcagtcg ttttcaatgc ccggtgcggt 19380

8068

-59-

ttcgctctgc ccggcacttt ctgccgggac aatgctcaat ccgctacctt ctttcgtctg 19440

aacgacagga aacaggctac tcggctccgg ctcccgctca caccccggca agccggacca

19500

caagcgacag cctatgcggt agtagcccat gcggtgtgta ctcagtcgtt ttcaatgccc 19560

ggtgcggttt cgctctgccc ggcactttct gccgggacaa tgctcaatcc gctaccttct 19620 5

ttcgtctgaa cgacaggaaa caggctacat taagcgtagt ggtatcctga gtagcgcggg

19680

acacgagaaa tcttgcgtga atctgccggg accatccggt aaggctaaat actcccgaga

19740

gaccgatagc gaaccagtac tgtgaaggaa aggtgaaaag cacttcgaat agaagagtga 10

19800

aatagtccct gaaaccgtgc gcctacaagc ggtcggagca aacctcctca cgaaatgcga

19860

ttggttttaa cgtgttaagt aatgcggcgg aaacgaggc tacccctact accaacacca 19920 15

acttgaagaa caccgatttc gacgtgttcg cttttacggc ggatggtact gccttcatgg 19980

gaaagaacga cacggaattt gaacatgacg gagtgaagat cgtgtacaaa aatggccttg

20040

gtggcttccc aactataaaa cgccatcatg tcttcactaa ccgttccggg attgaacgcg 20100

taaaagtcca aagcctcggt aggccaataa cgaaggtcgc tcgcattgtc ataatcccac 20

20160

8068

-60-

ttaccatttt tgtacacgat cttcactccg tcatgttcaa attccgtgtc gttctttccc 20220

atgaaggcag tctttgccct ggaatgtttc ctgtaccagt tccgaaacgc tcttgttcag 20280

gttctttctt ccgtcgtact gggttatcag aaccccggcg atcgaaagat ccgagttcaa 20340

acgttgctgc accttgtgga ctacctgcat aagtttggcc attccacgca ttgccaggaa 20400

ttgagcctga accgggataa tcaaccgagt gtcgcaaacg cacctgatcg caccggaaaa 5

20460

ggtgatttat atagattacg gcgatacctg catacaggta agcaaggccg agaataccga

20520

gaatatcgtg cgaatgatcg cagccacggg aaaggtggag gaatttccca ggcagacaaa

20580 10

cgtgtcgctg gcgaccgaag gggggaagtt ctacacgttc aacgtgatac cttattaata

20640

ggtcgtgtag cagacttgtc agtttatgta tgccgtgctg actacactca taaggcggaa 20700

tatacattga tcaatgaact gtcttttgag aagaagctgc ctaatctttg taccgtcatc 20760

aacggcgtag acctgaagaa gcgaaaatat ggttattact acggctacgg taagtatggc 15

20820

aaaccgtatt cgcctttcat cgcaccgtag atcgtttggg gaagctccgc agagaagccc

20880

agcgattcgg tcaggttggc ctgcccgtca aggtcgatca aaagaacctt gtaccctttt 20940

tgacgtaacg caccgcccag gttgatcgtg gttgtggtct ttcctactcc ccccttgtga 21000 20

ttcaatacgg agattacttt tgcgcctttg ataaggtggg ctaagataag ctcccgtccg 21060

8068

-61-

gcctcgttga ttaactccgt ttcaacggcc gagagatcca ggcaggaggg aacgacgcta

21120

aggccgtcct tatgctcgta gatcggcagg tcgtattcgc ctttcatcgc accgtagatc 21180

gtttggggaa gctccgcaga gaagcccagc gattcggtca ggccactact aggggaatca 21240 5

ttattttt cttttcctgc aggtactaag atgtttcagt tccctgcgtt agcctccatc 21300

aaagatggat gacattcctt cagaatgccg ggttgtccca ttcggaaatc tctggatcaa 21360

aggttatttg cacctaccca gagcttatcg cagcttatca cgtccttcat cgcctccgag 21420

actacgatat aatcggctaa aggagaatag aaagccctgt cgccttgctg ctcccgtatc 21480 10

gggcaaaacc agcttttcgc ctccagcatg gcatctattt cggggtgcgc ctctccggtt 21540

gtcccgtcgg gctgctctgc ctgtccccct ctgaacttct cccttaacgc ttcccattct 21600

tccggcctca cgtccgaaaa acgcaaacca ggtcggtacc ttcgcccgat gctccctgat

21660

tacccatttg agtaactact ccggtagagg cggccagctt ggtcagcaaa cgggattcgt 15

21720

aaacggagtg agtcaacggt ttctggcaat atacgtgttt gcccattgtc atagcgtctg 21780

ccgtgatgat ggcatgagta tggtcggcgg tagcaatgat tacgcacagt actggttcgc

21840

tatcggtctc tcgggagtat ttagccttac cggatggtcc cggcagattc acgcaagatt 21900 20

tctcgtgtcc cgcgctactc aggataccac tacgcttaat ttgacttcgt ataccggact 21960

8068

-62-

atcaccgtct atggttcaac tttccagagg attctactca tcaaatgtct tgcgacatcg 22020

tggtcctaca atggaagcta acgcagggaa ctgaaacatc ttagtacctg taggaaaaga

22080

aaataataat gattccccta gtagtggcga gcgaacgggg aatagcccaa accacccatg 22140 5

ttacggcatg tgtggggttg taggaccacg atgtcgcaag acatttgatg agtagaatcc 22200

tctggaaagt tgaaccatag acggtgatag tccgggcgta tatgttcggc tatcccgaaa

22260

aacattcctg ccagggctgc ggcgaactcg gccgttaatt cctccttgcc gtattcctct 22320

gatccgaacg ggtgcgcaag atcccggttc aatcgggtgg ggtgtcccgt ggaatgtccc 10

22380

atttcatgca gaagcgtttc gtaaaagctc tgcatatcga cgaactgcga gcgaagcggc

22440

atcataattc gcaatggggct gacaagatga tccaggtcgg actgatgccg tccgacaccg 22500 15

gggaggccgg aggcaaaagg acaggccaga gcattacgca ttatatcatt ccgggaggga

22560

agttcgagca ggttttcaat acgctaagcc gggaggatct gcaaaacttg cggctaggt

22620

acaagccgac tttggcggcc gtacctcatt tgctttattt caggacttcg cccttctcgt 22680 20

tgaagaacac ttcgctgtcc gtgccttctg catcggtaaa tgtcaccttg taggtctttg 22740

8068

-63-

tgccttcctc gctttcctca actgcggctt ccttgattgt caggtctgcg aaatccttct 22800

tgatcgtgtc ctgaaccgcc tgcggcagat cctttacctc gattggctta tatcattgta 22860

gcccaggctc aaagcgattt cggcacggag ggccttgacg gtctccatag tgatgcgcca

22920

cccgccttcg gggaggtttgt gtaaaaagta agaatcaagt gttctttgac atattgtatt 22980 5

aaaaaggcaa tgctctttat ctctttattt tggtatttct attgttgtcc tttggcgaat 23040

gaccgctatt aggtatactt aaggtagtac aggaatatta acctgttctg ccatcggcct 23100

caccgttcgg ctgagcctta ggacccgact aaccctgatc cgattagcgt tgatcaggaa

23160

accttagtct ttcggcgagg gggtttctca ccccctttat cgttacttt acctacattt 23220 10

gcttttccac acgctccagc aaagctcacg cttcaccttc gacgccgaga aacaaatacc

23280

gattactctg aattggaaga acagctcaat aatcttgtgg aagcattgta tcaatgacat 23340

attgttgacc ctcaaaagag ggcttcgata ttgtcattgg caatccaccg tacggagcga 23400 15

aatacgacaa ccaaacaaag aggtattata agaataccta tgtgacggca aatagcatcc

23460

gaggattaca gaacgaagac ctgatcacca cgggcaaggt cctgagtagt cggatgatcc

23520

tccagcatat cggaagtatt cttcttagtc tcttcacgca ggcgggattc gttgatgtcc 23580 20

gtgcccgttg atttcgaggt gtttacattg ttctgctgct cgtatagctg cttcacacgc 23640

8068

-64-

attgcctgtt ctttggttac ccccttacgg gctagttcgg aagcaaacgg gaagaacatc 23700

gccttaaccc tccggggcaa ttacaccaag cggctctaca agatcatttg cagccaacgg

23760

gacagacggg aggattatta ctcgatcgac caattctgca aagacctgga gatcccggcc 23820 5

tcctactcga atgcacagat cgaccaaaag gttttaaggc ctgcacagac acgaatcaag

23880

gaaagcgagg ccgatgtatg ctcccgtctg tcccgttggc tgcaaatgat cttgtagagc 23940

cgcttggtgt aattgccccg gagggttaag gcgatgttct tcccgtccct tgtaccgccg 24000

acacccgtac cgtagtagag caggaaaggg atcgcccagg ggttgagcgt caggggctacc 10

24060

cggtttgtgc ctttgatgtt gtgtaccgtc gttatcacca ccccgaacgt ttccagagtg 24120

agggaaatac aaaaatacag caaaatccat ataaaaaaga atcaatggca tgggcagcat

24180

ggattattgc aaggttagga gcatggagtg catacaagag ccagtccatt ccaggatata 15

24240

ttacctttaa gaatggactg gatagatttt atacacagtt tgaactgtat gagttaatca 24300

gctaagactt gtgtataaag ggtagcttcc gacaagcttc ggggatagtc ataaagaaac

24360

gaatgatatc ggggtgagtc actgtgacag gaccgccatt ctcaatctgt tccttaaaac 24420 20

8068

-65-

ggggaattac agaaccgtta ctacccaaga cgttaccaaa gcgggtagtg ataaatttgg

24480

tatggccttt tacttttccc tcacggatag cacatcccag actctgtaca tagatttcgg 24540

ccaaaagagt catcataagc tgtcgattct acaatataag ctgtagactg ttcataacct 24600

ataatttggt caagcctaca aaacgtccat ccatcaggca actgcgtata atgcccgtta 24660 5

tcacaaggtg tgaagtcggg atttatacgc ttcaacagct taattgctgg ctcttcattg 24720

ggatcttgtg gtactagctt accatgtatg gcaaggtcaa gacctcctgc tcatgggatg 24780

cccagaaaga gcaaaaaata accattggtg tatatcgttt gaccatgaag tccaattctg

24840

acaacttccg tcagagtgcc attcaaggga ttatgaagcg tatcaaggcg aagggtgcta 10

24900

ctattgtgat tttcgagcct actatgcaag atggtgaaac attctttggt agccaagtgg 24960

tcaataactt aatcaaattc acctcctgct catgggatgc ccagaaagag caaaaaataa

25020

ccattggtgt atatcgtttg accatgaagt ccaattctga caacttccgt cagagtgcca 25080 15

ttcaagggat tatgaagcgt atcaaggcaa aggggggctac tattgtgatt ttcgagccca 25140

ctatgcaaga tggtgaaact ttctttggaa gtcaagtgat caataatctg gtcgagttta 25200

cctcctgttc atgggatgcc cagaaagagc aaaaaataac cattggtgta tatcgtttga 25260

ccatgaagtc caattctgac aacttccgtc aaagtgccat tcaagggatt atgaagcgta

25320 20

8068

-66-

tcaaggcgaa gggtgctact attgtgattt tcgagcctac tatgcaagat ggtgaaacat 25380

tctttggtag ccaagtggtc aataacttaa tcaaattcac ctcctgttca tgggatgccc 25440

agaaagagca aaaaataacc attggtgtat atcgtttgac catgaagtcc aattctgaca

25500

acttccgtca aagtgccatt caagggatta tgaagcgtat caaggcaaag ggggctacta 5 25560

ttgtgatttt cgagcccact atgcaagatg gtgaaacttt ctttggaagt caagtgatca 25620

ataatctggt cgagtttaga tctcctttcc gtttttgtaa acggtcacta cccactgcat 25680

cggctcgttc acaacgccgt cctctccgtc cacgacacca cggaaacgg caaactcgat 25740 10

cgcctttccc gtcgtgctta acgtcacctt ttcgacggcc agttcttcat cgcttagaat 25800

caccgggctt gcgaggcttt cccccgtcgc cccgtctttc aactgcgtac cgttggcaag 25860

atccccaggg atgcgaacag gattattttt gttttcgtgg ccttatccat agtgttactt 25920

tttttcaggt tcttgttcta tccggacaat ctgctgtata aactggttaa agaaaaatcc 25980

cgtcacgttc tccggaaatt gcggcgtggt tctcacgatc tcccctttcg tcctgataag 26040 15

aaaccttagc ttctgccccg aaacgccgta aatcgtcagg gccgtgtctc ttgagcggaa

26100

acgaaaagaa cggaacacga taaaaaagaa aggagaatta ccttgaaaag tcttaaatat

26160

aggtttctac acacactcgt gtgtgtgtgt gtgtgtgtgt gtgtgtgttt ataaaaaaaaa 26220 20

8068

-67-

tcaatatttc caactttttt ctgttttttt tgcatataac ttactataaa atatctgcta 26280

ccccagaaag agcaactaac caaaacgttc tccggaaatt gcggcgtggt tctcacgatc 26340

tcccctttcg tcctgataag aaaccttagc ttctgccccg aaacgccgta aatcgtcagg 26400

gtggaagtga aagccacctt gtacggctca ttgtccccgg cgatcgtctg gatgctgtct 264605

atctcgcatt tatagaccgc cccgttctgc accgcatcaa aataggcctt atcattataa 26520

tactttgaga caactgcgaa agctggtaaa agctctttcc gaactcgacg acgatctgtt 26580

tataattctg ctcgatgttc tgctggatga tgttcaacga cgtaaccgac tttccccccac 26640

ccgtcgatgc gacgataatc atgttacgtg ccggaatgcg tttcttatct gcgtcccaaa 26700 cgtcctttcg aatcggtgtt tgatacagcc gttcgttaaa caagatcccc tcctcggacg 2676010

aggattgttg atcatggtat gaagcatctg agtcgcaacg atcaccggtt tctttgccag 26820

gatacatttg cggatcagca cacgctggat acccggaata cgttcctgcg gcacttcgat 26880

acccaggtca ccacggggcta ccatcacgcc gtccgccact tcaagaatct cgtcgatgtt 2694015

gtccacccct tcctgattct caatcttggc aataatcccc cggccgatcc gcatcgccgg 27000

aagcgacggg gacgaaacgg aagaaccgga agatccggac gagggggaga gcaaaagcgg 27060

aaagcggaag aaatacacct gtgggtgcgg ctgtaacgtg tggggaaaat ccggggctggt 2712020

8068

-68-

gttaaggtgc ggactgtgcg acactgattt tacggaacaa taggaaacag tgcaaaggtc

27180

agaagccccc agtaaaaacc ccgcgtattt cttccgcttt ccgcttttgc tctccccctc 27240

gtccggatct tccggttctt ccgtttcgtc cccgtcgctt ccggcgatgc ggatcggccg 27300

ggtaggtacg gccgccaaag tcggcttgta cctaagccgc aagttttgca gatcctcccg 5

27360

gcttagcgta ttgaaaacct gctcgaactt ccctcccgga atgatataat gcgtaatgct 27420

ctggcctgtc tcccgtgtct cttgagcgga aacgaaaaga acggaacacg ataaaaaaga

27480

aaggagaatt accttgaaaa gtcttaaata taggtttcta cacacactcg tgtgtgtgtg 27540 10

tgtgtgtgtg tgtgtgttta taaaaaaaat caatatttcc aacttttttc tgtttttttt 27600

gcatataact tactataaaa tatctgctac cccagaaaga gcaactaacc aaaaactttt

27660

ggttagttgc tctttctggg gtagcagata ttttatagta agttatatgc aaaaaaaaaca 27720

gaaaaaagtt ggaaatattg atttttttta taaacacaca cacacacaca cacacacaca 15

27780

cacacgagtg tgtgtagaaa cctatattta agacttttca aggtaattct cctttctttt 27840

ttatcgtgtt ccgttctttt cgtttccgct caagagacac ggacacgtaa tgaacgggtg 27900

taggcatcgg cttcaaagcc gccggcatat ttgattaaag tggcaaggtt ctcttctttc 27960

ttcatttcaa aacgcatagg acgttttacc ttgccgctga tctttaccaa tacatcataa 28020 20

8068

-69-

gcgggaacaa tcacgacgtc accttcctga aggcggatgt catcctgtgt gttgcctttc 28080

atgataaatt cgtagacgtc gatggtggca acgaggccgg acgggagctt atcttagccc

28140

accttatcaa aggccaaaag gagaaattcg attatatcct gatcgactgt cctccctcgc 28200

tgtcgctgct cacgcttaac gcactgacgg cctcggatcg gttgattatc ccggttcagg 28260 5

ctcaattcct ggcaatgcgt ggaatggcca aacttatgca ggtagtccac aaggtgcagc

28320

aacgtttgaa ctcggatctt cttgaccttg ccatacatgg taagctagta ccacaagatc 28380

ccaatgaaga gccagcaatt aagctgttga agcgtataaa tcccgacttc acaccttgtg 28440 10

ataacgggca ttatacgcag ttgcctaatg gatggactgt tgcacctatg caagtactat 28500

gctctttggt tgatggtgat aagcaaaaag gaatagaacg aataaatctt gatgtcaaat 28560

atttgcgtgg tttcgactgg accaagattt ccaatcatga caagcctgaa ggcatgaggg

28620

tcgtatttta tccgaccgat gatgaaagca acacgtggat atttgatttc cccggaggag 28680 15

aggatgggga agtggagctc cccgagaatg attaccgggt aatttgcttc aactacgata

28740

ccgacgggat ggtttggaaa gaaaacggca gttacacgct ttttactgcc gatacgcgtg

28800

atgaaccaag agcaagattc ttgatcttgc cattcacgga aaacttgtgc cgcaagaccc 20

28860

8068

-70-

aaacgatgaa cctgctatcg aattgttgaa acgtataaat cccgacttta caccttgtga 28920

taacgggcat tatacgcagt tgcctgatgg atggacgttt tgtaggcttg accaaattat 28980

aggttatgaa cagtctacag ctttatattgt agaatcgaca gcttatgatg actcttaacc 29040

aagagcaaga ttcttgatct tgccattcac ggaaaacttg tgccgcaaga cccaaacgat 29100 5

gaacctgcta tcgaattgtt gaaacgtata aatcccgact ttacaccttg tgataacggg 29160

catagtggga agttacctta taaaatacct aagacatggg catggtgtag tcataattct 29220

atcttagata tatctggagg atcacaacct gcgaagagtt attttgaaaa gccaagagca

29280

aaattcttga ccttgccata catggtaagc tagtaccaca agatcccaat gaagagccag 10

29340

caattaagct gttgaagcgt ataaatcccg acttcacacc ttgtgataac gggcatagtg 29400

ggaagttacc ttataaaata cctaagacat gggcatggtg tagtcataat tctatcttag 29460

atatatctgg aggatcacaa cctgcgaaga gttattttga aattcatgtt cagatacatt 29520

ttttttcaaa ttcaggggtta aatcgaaaaa aagtaggttt ttatttgttt aatacatgtg 29580 15

tttttgtcta tctttgcgtc aaatttaaat ccgttaccta agaagtaaca caccagcatc 29640

agtgctgatt atcaaatttt taaccattca aattcgacct aaagggcaag tcttcacgta 29700

atgcaaattc ttacgattta cctctgtacg ctctttaaag agcgtacaga ggtaaatcgt 29760

aagaatttgc attacgtgaa gacttgccct ttaggtcgaa tttgaatggt taaaaatttg 29820

ataatcagca ctgatgctgg tgtgttactt cttaggtaac ggaaaagtac acttcataat 29880 20

8068

-71-

aaatcggggag gaaaaagtcg aaaagtaccg actaatgagg gttgagagca tcttggcttt

29940

agagaaagta gagattctta ggaaaattgg ataccagcgt tttgagtgtg ctacgccttc 30000

ccctgtccca taaataggcc cagcatttag tgatttctct tttgttaaaa tcatactttt 30060

ttacccccatg tttttccgtt acttcttagg taacggattt aaatttgacg caaagataga 30120 5

caaaaacaca tgtattaaac aaataaaaac ctactttttt tcgatttaac cctgaatttg 30180

aaaaaaaatg tatctgaaca tgaaatacca gcgttttgag tgtgctacgc cttcccctgt 30240

cccataaata ggcccagcat ttagtgattt ctcttttgtt aaaatcatac ttttttaccc 30300

catgtttttc cgttacttct taggtaacgg aaaagtacac ttcataataa atcgggagga 30360

aaaagtcgaa aagtaccgac taatgaggggt tgagagcatc ttggctttag agaaagtaga 10

30420

gattcttagg aaaattggcc aattaccgtc ttggtcccgg tgatgaagtc atcattgata 30480

tctggggtgc gagccagaac acgatccgcc agcaaatctc tcctgaaggt actatcaaca

30540

ttcagaagat cggccctgtc aaccttagcg gtatgacagt ctctgccgcc aatgactatc 30600 15

tgaagaacgc cctgaataaa atatataacg gtctgaacaa cacgaccgat ccaacttccg

30660

acatccgtct gacagggaaa accgggagaa ggccgggaaa ctgcaaacgg atctcgaaat

30720

agcccggcag gagaaaggaa ctccggccgt cggatgcaat acgcacaaga tcctggagat 20

30780

8068

-72-

cgtggagcgt atcgacgagg tgaagaagat accgacattc aacgatacgg tttatgagat

30840

agaccgtaat acgctggata tgtgggtgaa aaggttaaag gacgaactaa agagataagc

30900

ctatgtttgc gggggaaagt cggttacgtc gttgaacatc atccagcaga acatcgagca 5

30960

gaattataaa cagatcgtcg tcgagttcgg aaagagcttt taccagcttt cgcagttgta 31020

cccggacagg tcgctgcata ttgattatga cggcagcagc ccgttgggga tcaatccgtt

31080

ctatacggcc gggaagcagc cggacaacga gaagataaag acgcttgtaa acctggtgct 10

31140

taaattcttc agattaatgt gatgggagaa gtcgtacagc ccggtaccta cgccctttct 31200

tccttctcta ccgtcttcca tgcgctttat cgtgcaggcg gtgtgagtga tatcggtagc 31260

ctccgaaacg ttcaattagt acgcaacgga aagaatatcg ccaccatcga cgtctacgaa 31320 15

tttatcatga aaggcaacac acaggatgac atccgccttc aggaaggtga cgtcgtgatt

31380

gttcatgcga agaaatactg ggattaccgc aagatgtacg atgaaatggg caaatccatt

31440

gacggcgtaa tcattgctac cgccgaccat actcatgcca tcatcacggc agacgctatg 20

31500

8068

-73-

acaatgggca agcacgtata ctgccagaaa ccgttgactc actccgttta cgaatcccgt

31560

ttgctgacca agctggccgc ctctaccgga gtagttactc aaatgggtaa tcaggggagca

31620

tcggctttat aatatcttta taggctcgat catcggccgg gaaaacaacc tgaatccgga 31680 5

ctacctgttt ctttcggatc tgcattcgtc gctctgcatg gggatcaatt actctacgtt 31740

ccgcagcgac aaggagggga tcttgtttaa cgaacggctg tatcaaacac cgattcgaaa

31800

ggacgtttgg gacgcagata agaaacgcat tccggcacgt aacatgatta tcgtcgcatc 31860 10

gacgggatgc ccgttatcac aaggtgtaaa gtcgggattt atacgtttca acaattcgat 31920

agcaggttca tcgtttgggt cttgcggcac aagttttccg tgaatggcaa gatcaagaat 31980

cttgctcttg gtttgcttta tgatggtttg caaatttact ttgctatgtt ctatttggtc 32040

gattaaagca aacaatttct ctatttccat tacaatgcgc tgttgctcac taagaggtgg 32100

taaaggaaag cacacaagct attgatattc aaccatacag catacctacc actccggctt 15

32160

tcagccactc ttccttcctg aagaggggag tttagttact tttgacacac cttcataaag 32220

ccagatgtac tgtccggggt atatttatga taattcaacg gtaggattgt gaatggttaa 32280

gccaccgtct accacaatcg tctgtccggt gatgtatcgt gcatcgttgg aggccaggaa 32340 20

tgcaatagtg ctgaggttgt ccattccttc cagcacggct tcgtccgtaa gtgacgagat 32400

8068

-74-

ccatagacgg cggtaggatt tcctgcattc cagataccgg taaaggtacc tgaacaccat

32460

ttccccctcc cgggagggggg aaatggtgtt caggtacctt taccggtatc tggaatgcag 32520

gaaatcctac cgccgtctat ggatctcgtc acttacggac gaagccgtgc tggaaggaat 32580 5

ggacaacctc agatattgta aagcaggaac tcgttgaaca aggtattcat attgattttg 32640

aagatatgga cttgtctgca aacagtcagt tcttcctctg gcatacctgg ttccatgatg 32700

ttttctcacg accctcaaaa gagggcttcg atattgtcat tggcaatcca ccgtacggag 32760

cgaaatacga caaccaaaca aagaggtatt ataagaatac ctatgtgacg gcaaatagca 32820 10

tccgaggatt acagaaactg aaccgttgtc ataaccgttt cggctggtgg ggagacgggg

32880

aaacgataag gcgggcattc caggacaggt cggtactgaa aaacgtaaca gacagtgaga

32940

ctttatgactt tacccccccc ccacatggga gaactattac aggttgactg atgcaggcaa 15

33000

ggggctagga ctgacgcgga gccaacataa ttatgaccgg atgacactgc tatatatcat

33060

ggacaaaggt tatccgagaa gacccgaacg atgaacctgc atcagttctg ctcgaacgaa 33120 20

8068

-75-

tcaaggctga aaaagaacga ctgataaagg aaggcaaaat caagcggagc aagaagtctg

33180

caaagacttc cgatacgcca cattatgaga acgtgccgtt tgaaataccg aattcatgggg

33240

tgtggacaac gattgaagaa atatgctcaa agataggttc cggtagcacg ccaaggggaa 5

33300

gtaactattc tgcgaacggg atcagacccg aacgatgaac ctgcatcagt tctgctcgaa

33360

cgaatcaagg ctgaaaaaga acgactgata aaggaaggca aaatcaagcg gagcaagaag

33420 10

tctgcaaaga cttccgatac gccacattat cagaatgtgc cgtttgaggt gccgagttca 33480

tgggtatggt gcaaattgga ggattatgtt aaaagtgtga ctgatggcga tcatcaagca 33540

ccgcctaagt cagatattgg catcccacaa acggtaatca gtgaacaacc catatcctat

33600

ttcaaggata aagaatatct atcattcaag gaggttgcaa ctttattggg gctgagcaaa 33660 15

caagccgtat ataaaatggt atatgccaca ttatgagaac gtgccgtttg aaataccgaa

33720

ttcatgggtg tggacaacga ttgaagaaat atgctcaaag ataggttccg gtagcacgcc

33780

aaggggaagt aactattctg cgaacgggat ccaaacggta atcagtgaac aacccatatc 20

33840

8068

-76-

ctatttcaag gataaagaat atctatcatt caaggaggtt gcaactttat tggggctgag 33900

caaacaagcc gtatataaaa tggtatatgc cacattatca gaatgtgccg tttgaggtgc 33960

cgagttcatg ggtatggtgc aaattggagg attatgttaa aagtgtgact gatggcgatc 34020

atcaagcacc gcctaagtca gatattggca tcccataatg cccgttatca caaggtgtga 34080 5

agtcgggatt tatacgcttc aacagcttaa ttgctggctc ttcattggga tcttgtggta 34140

ctagcttacc atgtatggca aggtcaagaa ttttgctctt ggtttgcttt atgatggttt 34200

gcaaatttac tttgctatgt tctatttggt cgattaaagc aaacaatttc tctatttcca 34260

ttacaatgcg ctgttgctca ctaagaggtg gtaaaggaat acagagcttt ttagtttctc 34320

ccgcttgaaa cttttgtttc tcctgcttgg aactaaagtt tcatcggctt gaaactttag 34380 10

tttcaaagcc gtgaaaccaa agttccggac gcttgaaaac agtggttcca gccgatggaa

34440

tgaatgaaac aaggcaggaa actgatccct tacttatatg attcaattaa cttgaccgca 34500

ccaactgttc gattaacctg ctcttccaag aaacaataaa tcatctgtac ttctgctacc 34560

tccaactctt cgacatcccg aagcgtgaaa acgagtttct gctggggagg cagttcgttg 34620 15

gtatatcgca atatcagttc tttcaactgc ttgttggaaa gagatatctc tttccaacaa 34680

gcagttgaaa gaactgatat tgcgatatac caacgaactg cctccccagc agaaactcgt

34740

tttcacgctt cgggatgtcg aagagttgga ggtagcagaa gtacagaaac tgaaccgttg 34800 20

8068

-77-

tcataaccgt ttcggctggt ggggagacgg ggaaacgata aggcgggcat tccaggacag

34860

gtcggtactg aaaaacgtaa cagacagtga gacttatgac tttacccccc cccccacatg

34920

ggagaactat tacaggttga ctgatgcagg caaggggcta ggactgacgc ggagccaaca 5

34980

taattatgac cggatgacac tgctatatat catggacaaa ggttatccga gaatatattg 35040

ccataaacac gagctccccc atcgatataa acagtagttc ctgaggggac aaatagagta

35100

tcattaggaa gattatgcac accgggacca aaataaatca aattggaccc tttttttttc 35160 10

ttgagagccc tttggatttc tttatcggaa ggacgaaatt tatcaatcgg attcgcaaaa 35220

agatgaagat tgtgaaaaat atctccattg acctctactg agagattgcg aggacgccca

35280

cctcgtcggc cgcctccttt gtcgcttccg ccttgatgtt caagggcaca tatataccgg 35340

gcagtccgtc cctgtcgtac acggtctttt gcatctcata gatgctgttc ccgatccgga 35400 15

cggattcaac cgttatattg atcctgtcct gtgcgagctt caccaccccg aaaacggccg 35460

tccccttgtt aatcaccatg ccgccgggca gttgcatttc ttggagcgtg acaagtttta 35520

tcaatatatt gccataaaca cgagctcccc catcgatata aacagtagtt cctgagggga

35580

caaatagagt atcattagga agattatgca caccgggacc aaaataaatc aaattggacc 20

35640

8068

-78-

cttttttttc ttgagagccc tttggatttc tttatcggaa ggacgaaatt tatcaatcgg 35700

attcgcaaaa agatgaagat tgtgaaaaat atctccattg acctctactg agagattgcg 35760

aggacgcgaa gagtgacgtg gagacggagg cgtgacagcg ccgcggactg acggaatagt

35820

ccgttgaagg gtgtagatgc tgatcatccc aggcaaatcc gggatgagag tcgaacctga 5

35880

tagtatggaa cgttccatac tatcaggttc gactctcatc ccggatttgc ctgggatgat 35940

cagcatctac acccttcaac ggactattcc gtcagtccgc ggcgctgtca cgcctccgtc 36000

tccacgtcac tcttataaag ctatgcttta gaagtcgtaa agcatagctt tagccaatac 36060

aaaacgccct cgcagtctac aacacttatt acctgttacc taatacttat tacctgctca 36120 10

tggttcgccc aacgcatcca caatcaccct tacctccagc ggagtgtaag aacggtgctg

36180

cggctgataa cctaaatcgg acaggcgttc ctgaagaccg ggacagcgga caatccattt

36240

attcattttg cggtaagcgg atatattgcc ataaacacga gctcccccat cgatataaac 36300 15

agtagttcct gaggggacaa atagagtatc attaggaaga ttatgcacac cgggaccaaa

36360

ataaatcaaa ttggaccctt ttttttttct tgagagccct ttggatttct ttatcggaag 36420

gacgaaattt atcaatcgga ttcgcaaaaa gatgaagatt gtgaaaaata tctccattga

36480 20

8068

-79-

cctctactga gagattgcga ggacgcaaag aaagaagccg agtctaacat caggtagaca

36540

aggttgaact agtcctatag ctcagttggt tagagcgcta cactgataat gtagaggtcg 36600

gcagttcaac tctgcctggg actactccga acaaaaattg tcgttgtcaa ttcattattg 36660

caatgttcaa ttactcttgg gggattagct cagctggcta gagcatctgc cttgcacgca 36720 5

gagggtcaac ggttcgaatc cgttattctc cacaaggcaa atgtgaaggt gctgcatggt

36780

tgtcgtcagc tcgtgccgtg aggtgtcggc ttaagtgcca taacgagcgc aacccttatc 36840

tttagttact aacaggtcat gctgaggact ctagagagac tgccgtcgta agatgtgagg 36900

aaggtgggga tgacgtcaaa tcagcacggc ccttacgtcc ggggctacac acgtgttaca 10

36960

atggggggta cagaaggcag ctacctggtg acaggatgct attcccgacc agagcaacgt

37020

tgatagtacg gcgcttacct aacgccaacc gtttcatatc ttcttctttt acagaaacat 37080

cttcgggcag accttcgtga tatacagctt tttcggcttg ttttttttgct tcttcctcgc 37140 15

tgactacctc aatcatttcc gcttcctgac gacgaagaga tatttcataa cctaagactt 37200

tatatttaat cgggtctttc agtggagcat tcaacaatac ttcaacaatt cccgaccaga 37260

gcaacgttga tagtacggcg cttacctaac gccaaccgtt tcatatcttc ttcttttaca 37320

gaaacatctt cgggcagacc ttcgtgatat acagcttttt cggcttgttt tttttgcttc 37380

ttcctcgctg actacctcaa tcatttccgc ttcctgacga cgaagagata tttcataacc 37440 20

8068

-80-

taagacttta tatttaatcg ggtctttcag tggagcattc aacaatactt caacaaaggc 37500

gagatcacct ttgacaaact cggttcgcaa caccctgcca tcgaacccga ttatgcttcg 37560

gtacagtccg tacttcacag tatcgacttc cctattctct acggatataa cgtagtgaaa 37620

aaggaccata cggaatgtct atctttgccg gtccaaaact ccggtatcta tggggaaagc 37680 5

agaacgaaat cactttcaca aacttcgacc agaaagggat tcatgaaaag ctgtatccgc

37740

tcaacccccac acatgccgta acatgggtgg tttgggctat tccccgttcg ctcgccacta 37800

ctaggggaat cattattatt ttcttttcct acaggtacta agatgtttca gttccctgcg 37860

ttagcttcca tcaaagatgg atgacattcc ttcagaatgc cggggttgtcc cattcggaaa 37920 10

tctctggatc aaaggttatt tgcacctacc cagagcttat cgcagcttat cacgtccttc 37980

atcgcctccg agattgtcat aatgacggaa atcaggaacg gatctttctt tatcttcgtc 38040

agctcaaaga cgataaaatc ccggttctgc atatcgttct ccagtgggga cggcttgcac

38100

acgttctcat aaaatcccccc ggcataaatt ccgaacacac gtgcaggaag ctgtctatat 15

38160

cgaagtattc cggcaggata ttcaaacgct catacagttt tttcccctct ctttggacgt 38220

acctgtaaaa gtccgggaaa caaaaataag taaaccggag gcaggaataa taaataataa

38280

agtaaacagc tgccagggtt agtaatattt ctagtcaaca catagcagct attagagata 38340 20

8068

-81-

aacaagtcaa ccattattag ggaagtacag agctttttag tttctcccgc ttgaaacttt 38400

tgtttctcct gcttggaact aaagtttcat cggcttgaaa ctttagtttc aaagccgtga 38460

aaccaaagtt ccggacgctt gaaaacagtg gtaaggcgag atcacctttg acaaactcgg

38520

ttcgcaacac cctgccatcg aacccgatta tgcttcggta cagtccgtac ttcacagtat 38580 5

cgacttccct attctctacg gatataacgt agtgaaaaaa ggaccatacg gaatgtctat 38640

ctttgccggt ccaaaactcc ggtatctatg gggaaagcag aacgaaatca ctttcacaaa

38700

cttcgaccag aaagggattc atgaaaagct gtatccgctc aaattcaggg atttcagttc 38760 acgacctttc agatgcataa atcccctgtc cagcggttct gccggatcta tcagcccatc 38820 10

acccggttct tcacccggac ctcccggatt ctcggtagac ggagtatata ctccgtctac 38880

cgagaatccg ggaggtccgg gtgaagaacc gggtgatggg ctgatagatc cggcagaacc

38940

gctggacagg ggatttatgc atctgaaagg tcgtgaactg aaatccctga attgtttccc 39000

ggacttttac aggtacgtcc aaagagagggg gaaaaaactg tatgagcgtt tgaatatcct 15

39060

gccggaatac ttcgatatag acagcttcct gcacgtgtgt tcggaattta tgccgggggg 39120

attttatgag aacgtgtgca agccgtcccc actggagaac gatatgcaga accgggattt

39180

tatcgtcttt gagctgacga agataaagaa agatccgttc ctgatttccg tcattatgac 39240 20

8068

-82-

aatctgcgtg ccacggatat tccggataat ggaaactgca ctctccaccg attccagaaa

39300

ctcggccagc ctgtcccggt ctgccttcgc cagtttctcg ctatacgcca acggggttggc 39360

ctggtacgct ttttcaaggc tttgcagtcc cgaaagcgta aaggacaata tgcagaagtg 39420 5

atgcaggtat tcccgtccgt cgaaatactt cctttcggcc gtctgtatat agccctcccc 39480

ctcgatcaca tacggaggaa gaagtaatgt taatccagcc gaataacgta acattcggcc

39540

agtactctgt gaccgagtgg caagaaaacc tcctgacgct cataagcgac cagatccagc

39600 10

aacacatgac cagggaaaac aactgcctaa agacctcttt aaccagcctg tcgtcgagat

39660

caaatgcgac gaagccgggg ggaagaacaa caagagcaaa gttctgaaag aggctatcgc

39720

catgatgcgg aaaaactttt cccgggttca ggattcccaa tgtatcgggc aacatataac 15

39780

gtctgatgct tgtctgcttc aagccatcca tcaactgaaa cacatattcg ggagaatctt 39840

tcattccgtt actccagtct tccagatatc tggaagactg gagtaacgga atgaaagatt 39900

ctcccgaata tgtgtttcag ttgatggatg gcttgaagca gacaagcatc agacgttata 39960

tgttgcccga tacattggga atcctgaacc cgtatccctt tcttctgccc gatccttatc 40020 20

atatcggaac actgtatatc ccttagtccc tcgtcgtcat ggaaaccgtt cacgtaccgg 40080

8068

-83-

aaaaggtgct gtttcacctc ggccacgttc aacggccgga tctgcgtgcc acggatattc

40140

cggataatgg aaactgcact ctccaccgat tccagaaact cggccagcct gtcccggtct

40200

gccttcgcca gtttctcgct atacgccaac gggttggcct ggtttgtcat atgcctcctg 40260 5

atagcgattg gcgcggtagt tcagaccggg gatatcgatc atggcagcaa atccgttggc

40320

tagaacacaa gtcacttggt ccatgccgca ggtaacgggg cgggtagggt cttcacggtg

40380

gcagatatct tgcaggaact tggctacttt atatcctaca gggctgcatt gcgtggggac 40440 10

ttcattaccg atactccaca tcactacaca gggattgtta cgatagttgt gccggaggaa 40500

gaagtaatgt taatccagcc gaataacgta acattcggcc agtactctgt gaccgagtgg

40560

caagaaaacc tcctgacgct cataagcgac cagatccagc aacacatgac cagggaaaaa

40620 15

caactgccta aagacctctt taaccagcct gtcgtcgaga tcaaatgcga cgaagccggg

40680

gggaagaaca acaagagcaa agttctgaaa gaggctatcg ccatgatgcg gaaaaacttt

40740

tcctgtagat gttgatcatc ccaggcaaat ccgggatgag agtcgaacct gatagtatgg 20

40800

8068

-84-

agcgttcttc ggaacaatcc aatagtgcgt gtaagcatac tcccaagaaa atccgctaaa

40860

cttaatcctt aaggtacccg taccgcaaac ggacacacgt agtcgggttg aatatactaa

40920

ggcgcttgag tgattcacgg ttaaggaact aggcaaattg accctgtaac ttcgggataa 5

40980

agggtcccaa cgagaccacg tttgtccgct tcttccgtaa ggaaagaaaa catctcttca

41040

ttcttcttga acgtctcttc gtctacttcc agcgcaaacg gataatcttc cagtttgacc 41100

aacgatgcaa acggatgacc atggtcatcc gtttgcatcg ttggtcaaac tggaagatta 10

41160

tccgtttgcg ctggaagtag acgaagagac gttcaagaag aatgaagaga tgttttcttt 41220

ccttacggaa gaagcggaca aacgtggcct cctgatcggc tatgtgtccg gggtcgatgc

41280

cactcacttt caggtcgatg ggtttgctcc acgggccctt gatgtcattt gcccagatca 41340 15

cccagtttgt tcctttggcc ggataataga tgtacatcta ttatccggcc aaaggaacaa 41400

actgggtgat ctgggcaaat gacatcaagg gcccgtggag caaacccatc gacctgaaag

41460

tgagtggcat cgaccccgga cacatagccg atcaggaggc tgaaagctgc caatgaaggt

41520 20

8068

-85-

caatacaact tcctcagcga agtgaaggta tatggtgaca gagcgcagaa gttaaaagag

41580

attttcctcc gtcacggatt ctatctggta tatgacaatg acttggcgat ccgattgccg 41640

acggatttta cttcaccatc ggctatccgg gaatgacaag cggcgaactt gccaaagaac 41700 5

tgatgtacta tggagtgagc gccatttcac tggtcaccac cggaagccac ctactgttcc 41760

gaactgggta gcatggtctt caatctccgc ctgactggta aagagcccat cggctatgaa

41820

tccccaagtc gcatttacat tcgtaccgcg tgtctccatc caaggatagt ctaccggccg 41880

gtagactatc cttggatgga gacacgcggt acgaatgtaa atgcgacttg gggattcata 10

41940

gccgatgggc tctttaccag tcaggcggag attgaagacc atgctaccca gttcggaaca

42000

gtagctcact attatcccgg aagcagactt gaaaaacaat atgaataaca tctgagacta 42060 15

atgccatgat atcaacaaga aatgccaaga acataatacc aagaaacaat cgaaatccgt

42120

ggagctggat ccagctccac ggatttcgat tgtttcttgg tattatgttc ttggcatttc 42180

ttgttgatat catggcatta gtctcagatg ttattcatat tgtttttcaa gtctgcttcc 42240

gggataatag tgagcaaccc cctcgccgaa agactaaggt ttcctgatca acgctaatcg 20

42300

8068

-86-

gatcagggtt agtcgggtcc taaggctcag ccgaacggtg aggccgatgg cagaacaggt

42360

taatattcct gtactacctt aaagagtgac gtggagacgg aggcgtgaca gcgccgcgga

42420

ctgacggaat agtccgttga agggtgtaga tgctgatcat cccaggcaaa tccgggatga 5

42480

gagtcgaacc tgatagtatg gaacgttcct gaaagctgcc aatgaaggtc aatacaactt

42540

cctcagcgaa gtgaaggtat atggtgacag agcgcagaag ttaaaagaga ttttcctccg 42600 10

tcacggattc tatctggtat atgacaatga cttgggcgat ccgattgccg acggatttta 42660

cttcaccatc ggctatccgg gaatgacaag cggcgaactt gccaaagaac tgatgtacta

42720

tggagtgagc gccatttcac tggtcaccac cggaagccac caaatatcat tcaattcgaa 42780 15

atagcgattg gcaatcacat tacaaacatc ttcagccact tttgcatccg tcagtccgag 42840

tttatctaca atcttttgcg aacggttgac gatagactcc acatatttaa atatgtggag 42900

tctatcgtca accgttcgca aaagattgta gataaactcg gactgacgga tgcaaaagtg

42960

gctgaagatg tttgtaatgt gattgccaat cgctatttcg aattgaatga tatttatata 43020 20

8068

-87-

ctaaatgctc cacgctatga tgacgacagg actctaagat gttataaaat ccaataagat 43080

tactttcaat ataggcatca gggttagtga tgctatagcg tacaccggct tgtgcagcaa 43140 ggttcacgac tacctgagga tggtagttag tgaaaataga ctcaacaatt tcctttttag 43200 caatactgtc ttttatgaaa acaaatctgt caccgtaagc agaca attct tgtaagcgtt 43260 catactttaa gcaacagtca tgtcgaatac ttttgcaatg gaagttccga tggctccttc 43320

ataagggatg tgtgctccct gaatgttgtc tgcgacaatt cgtccctgac gattggcggg 43380

accagcaagg taattgcaat taccttgctg gtcccgccaa tcgtcaggga cgaattgtcg

43440

cagacaacat tcaggggagca cacatccctt atgaagggagc catcggaact tccattgcaa 43500

aagtattcga catgactgtt gctcctaaga tgagcatgag tgttcttaac cctacgttaa 43560

aagtcagtgg caactttgat actccaatat ggaacggagc catttttcat caatcaacct 43620

tcaataacct ttttaccaaa ggactatcct aggatagtcc tttggtaaaa aggttattga 43680

aggttgattg atgaaaaatg gctccgttcc atattggagt atcaaagttg ccactgactt 43740 ttaacgtagg gttaagaaca ctcatgctca tcttaggctt cacggaattt gtccagttgg 43800 tagttcagaa tttcgctgtt actcattccg tgcgtatcat caagcagaga at caatatga 43860 aggtctactt caataatccc attttttccg ctctgaccgt ggttaaccac ggtcagagcg 43920 gaaaaaatgg gattattgaa gtagaccttc atattgattc tctgcttgat gatacgcacg 43980

10

15

8068

-88-

gaatgagtaa cagcgaaatt ctgaactacc aactggacaa attccgtgaa gcttcggaca 44040

tcgggcagaa gactaaacag tgtatccaaa gattcctcca tcttccagac agaccactgc

44100

atatcaaccg ttttatgttg cagaaataat cccatcgttt ttggtttata atttcttcga 44160 5

agaaattata aaccaaaaac gatgggatta tttctgcaac ataaaacggt tgatatgcag

44220

tggtctgtct ggaagatgga ggaatctttg gatacactgt ttagtcttct gcccgatgtc 44280

cgaagtagat aaggctaccg ggaagtttca tatcgtgata cacttcacca ttatcttcgc 44340 ccgcacgttt tacaagtaac actttgagtt gttctccgtc aaaaccaatc actacacagt 44400 10

ctactgatat gtacatatca gtagactgtg tagtgattgg ttttgacgga gaacaactca 44460

aagtgttact tgtaaaacgt gcgggcgaag ataatggtga agtgtatcac gatatgaaac

44520

ttcccggtag ccttatctat cgataccttt ttggttcagg aaggtgactg ggtacgtcaa 44580

ggagatactc ttgttgtgat caacagcccc gaaatacatg ccaagtatca gcaggtgaat 15

44640

gcattggagc aagtagccgt gcagcatgct gcacggctac ttgctccaat gcattcacct

44700

gctgatactt ggcatgtatt tcggggctgt tgatcacaac aagagtatct ccttgacgta 44760

cccagtcacc ttcctgaacc aaaaaggtat cgatcgctac ggaacgtctg atcaccattg 20

44820

8068

-89-

acggaagaaa gatcaagatc atcgaagaag aaaaactcaa gaaaataagc aagataggat 44880

aatacagacc ttatacgatc ataaaaagtg atctgaaact agtttcagat cactttttat 44940

gatcgtataa ggtctgtatt atcctatctt gcttattttc ttgagttttt cttcttcgat 45000

gatcttgatc tttcttccgt caatggtgat cagacgttcc gtagcgatga tcctttacat 45060 5

aatgcattgg ctgaaagaat gaacaacacc attaaaaacg gttggctatt cgactgtgat

45120

gatgagagct tcgagcaagt aagcaagcgc attgaagatg ctgtatatgt atatggcctc

45180

atcaagggat aaacatgagg aacctatgg aagtggtcag cgaaacggga ggattaacag 10

45240

cataataccc gctcgtcggg acgggtggtc ccgccccttg ccgctagggc gatccccgac

45300

cgagcatgag agcaaaaacg cattcaaatt acatggggga gatgtgtaga accaataaaa 45360 15

agcaaattaa agcgaaagaa ggctatttct ggtaactttt tgcataacat attggttaac 45420

tttgcactag tgcaaagtta accaatatgt tatgcaaaaa gttaccagaa atagccttct 45480

ttcgctttaa tttgcttttt attggttcta cacatctccc ccatgtaatt tgaatgcgtt 45540

tttgctctca tgctcgcaga caaatgtagt cactgcaata catgggatgg cggaaacagt 45600 20

aggcagttcc agcgtatttt tgaatactgt cgcccataac ccgagccaga atatatgcat 45660

8068

-90-

aaggtacata ccatagctaa gtacttagct atggtatgta ccttatgcat atattctggc 45720

tcgggttatg ggcgacagta ttcaaaaata cgctggaact gcctactgtt tccgccatcc 45780

catgtattgc agtgactaca tttgtctgcg ccggaaaggc gaagcctgct gccggaaaaa

45840

agaaagggac ggggaaacgg ataggtaagt caaaggtgga gaaggctaat aatcagttga 5

45900

ataggagagt gaaataagcc tttggagact gcgcccgggc gcagtctcca aaggcttatt

45960

tcactctcct attcaactga ttattagcct tctccacctt tgacttacct atccgtttcc 46020

ccgtcccttt cttttttccg gcagcaggct tcgcctttcc ggccttatcc agccttgaaa 46080 10

ttggaaaaat gcaattcaaa ttcaacgagt gtgatattgt agcgctatgc agaaatgtca 46140

tcgacatggt agagaaaata aagcagactc aagcggaagt acggttttcc ccctctctca

46200

gttcactgaa gctgaccacg gacagtgccc gcctgcaaca agtactgatc aatctgctta

46260 15

tcaacgccac aaagtttact gcacaaggca ctatcaccct ggaactggtg aaacaaacaa

46320

aatagaggtg atccgcaggc tttccggtgt ggaaatcgag cagacggcca ccactccgca

46380

gataaacgcc tatatcgagg cgaatatcta tgataccgaa cgttggccgg agtaccggaa 20

46440

8068

-91-

gttatgccga caggtggccg gagaggtgga aaccgtggcc gacatcttta cgctccagta

46500

tattttagtg gccgaactgg aggatcagac caggacggga aaggactgcc agccgcagcc

46560

gacagatccg aaaaaaaatag aggtgatccg caggctttcc ggtgtggaaa tcgagcagac 5

46620

ggccaccact ccgcagataa acgcctatat cgaggcgaat atctatgata ccgaacgttg

46680

gccggagtac cggaagttat accgacaggt ggccggagag gtggaaaccg tggccgacat

46740 10

ctttacgctc cagtatattt tagtggccga actggaggat cagaccagga cgggaaagga

46800

ctgccagccg cagccgacag atccgaaagg tacgatgaga atgaccggaa aatttgtgtt

46860

gctgcttgcg gctatgcttg ccctgtttct ggggcaggcg caggcccaac gctgcctgcc 46920 15

gggtatgaaa ggtgtgcagc taatggcgga tatggttgac ggtttttatt gcgggaagga 46980

acgtaatgat acgggattcg ctttcggact tgccgtttct acctatgcta agggaggaaa 47040

taaatgggca tcgggtattg aaatcatgcg gcggtattat ccccaccata aacagcagct

47100

gcagaagcat ctttcaatat actgatcgtt tcaatatcgt taggattcac attctgaagg 47160 20

ctctgctcaa ctccgtcgat cagcacataa ggttctcctt tattaataga acccgtacca 47220

8068

-92-

cgaatattga acttgatttc agcacccatt tcaccgccga caccatcagc gactgcatct 47280

gttgaaaaat tcaagcctgc gacattaccc tgaagggcac tggtcaagtc cgttaccgaa

47340

acagtagaaa cactagtagt gcctgtacac tgcgaatcgg agcagggaac ggcctttttt 47400 5

atcagcgata cacagttgct aacagctcgc catgtggtga aagcccattt ccaaagtgtg

47460

gcggcacctg ccgctattta tatcaatgtg gctggacaat ccctgctgtg tatgggagaa 47520

gaactgtcaa ttccaggaaa cgctattgat ttagcattgc tgaccgtagt accagaagca 47580 10

gactatcatg caaaaacagt agaaacacta gtagtgcctg tacactgcga atcggagcag

47640

ggaacggcct tttttatcag cgatacacag ttgctaacag ctcgccatgt ggtgaaagcc 47700

catttccaaa gtgtggcggc ccctgccgct atttatatca atgtggctgg acaatccctg 47760

ctgtgtatgg gagaagaact gtcaattcca ggaaacgcta ttgatttagc attgctgacc 47820 15

gtagtaccag aagcagacta tcatgcaaaa acctcctcac gaaatgcgat tggttttaac

47880

gtgttaagta atgcggcgga aacgaggggct acccctacta ccaacaccaa cttgaagaac

47940

accgatttcg acgtgttcgc ttttacggcg gatgggactg ccttcatggg aaagaacgac 20

48000

8068

-93-

acggaatttg aacatgacgg agtgaagatc gtgtacaaaa atggtaagtg ggattatgac 48060

aatgcgagcg accttcgtta ttggcctacc gaggctttgg actaaactta tgtacgtccg 48120

caggtatcgg ccgagatcgg gaagatcacg aacccggagc ttaaaaggat attgcaggac 48180 5

gagcagttta cggcggcaaa ccagatcgtc gcagccatga gggaacaagg gtacacgcac

48240

caggtaagga aggggggtgca ttccttttca cgggaggtg aagtgttcca ggttgaacac

48300

aggctcttga aagcgttcga acaacctctg tctgacgagc agctaaaaag cataacggaa 10

48360

acttatgtac gtccgcaggt atcggccgag atcgggaaga tcacgaaccc ggagcttaaa

48420

aggatattgc aggacgagca gtttacggcg gcaaaccaga tcgtcgcagc catgagggaa 48480 15

caaggctaca cgcaccaggt aaggaagggg gtgcattcct tttcacggga gggtgaagtg

48540

ttccaggttg aacacaggct cttgaaagcg ttcgaacaac ctctgtctga cgagcagcta

48600

aaaagcataa cggaccgcag gggattacgg ggacatcgcc ccggtgtggg ggatcgtcca 20

48660

8068

-94-

aaaggacggg gatatttacc gtttcgtccc ctctgtcgca cccctgaaag agaaataccg

48720

gatctccgac cgttacggct accggacgca tccgataagc ggtgaaaggc agtttcacgc

48780

aggcctggat atggcggcgg tgtatgcggc taccgtacac gccgcagcca gtgggacggt 5

48840

gacgttcgca ggtgaaacgc ccggatataa attctggatg ctcacaatag tgatatccgg

48900

attattgcca agattgagaa tcaggaaggg gtggacaaca tcgacgagat tcttgaagtg 48960 10

gcggacggcg tgatggtagc ccgtggtgac ctggggatcg aagtgccgca ggaacgtatt

49020

ccgggtatcc agcgtgtgct gatccgcaaa tgtatcctgg caaagaaacc ggtgatcgtt

49080

gcgactcaga tgcttcatac catgatcaac aatcctcgtc cgaaaattgg ttgtcgtatc 49140 15

gaacgcctat cagatcgaaa acctgatttc cccggttata tcgctcatgc tttccatttc 49200

gtcccggcgt ttcacgctgg cgaacaaagt gccgttcttc tactttctgg ctgaagcgac 49260

cacgttccgg atcgccgatt tcgagaaact gccgtccgtt ctaagggaat acctttgcag 49320

tttcgttttc ctcacgcagt cggcggcgaa gatcgagaag atatacggga aatatgacaa 49380 20

agaaaaatcc cgtcacgttc tccggaaatt gcggcgtggt tctcacgatc tcccctttcg 49440

8068

-95-

tcctgataag aaaccttagc ttctgccccg aaacgccgta aatcgtcagg gtggaagtga

49500

aagccgcctt gtacggctca ttgtccccgg cgatcgtctg gatgctgtct atctcgcatt 49560

tatagaccgc cccgttctgc accgcatcaa aataggcctt atcattataa tactttgaga 49620

acacggcatt cagaaagaag tgtcccaaga cagcccttac cgccgggtgc ggctcattct 5

49680

tcaagagatc gaaaaggacg ggcatagcgt ccctgaccgc tttcgggttc aacgggatat

49740

gttgcgatcc ccgtatatag acctgcccgg tacgataacc cacaagatcc tccctttgca 49800

agatccccac cgtaacgaac ggcatccaca tctgcatata ccagaccgga tgatccgccc 10

49860

ttaccgcttc ccctgcgttc tttcctttaa agaagtgtcc caagacagcc cttaccgccg 49920

ggtgcggctc attcttcaag agatcgaaaa ggacgggcat agcgtccctg accgctttcg

49980

ggttcaacgg gatatgttgc gatccccgta tatagccctg cccggtacga taaccccacaa 15

50040

gatcctccct ttgcaagatc cccaccgtaa cgaacggcat ccacatctgc atataccaga

50100

ccggatgatc cgcccttacc gcttcccctg cgttctttcc tttaacaaga tgcacgaaga 50160

tccggaaaca aattccgata catgtaccga tatgggatgc cgtaccgcaa gcgtttcaat 20

50220

8068

-96-

tcatttatct tgttctcccc gtttccactt gcttccacct cggaaacaat gccttgcaga 50280

agctccaccg tttccgattt accgggcatt ccgggatcat tctccaccaa acgcagcaat 50340

cccctccagt cacgccccac gaataccgac gttttcagcg tgtcgggtag cggcgagtaa

50400

caagatgcac gaagatccgg aaacaaattc cgatacatgt accgatatgg gatgccgtac 5 50460

cgcaagcgtt tcaattcatt tatcttgttc tccccgtttc cacttgcttc cacctcggaa 50520

acaatacctt gcagaagctc caccgtttcc gatttaccgg gcattccggg atcattctcc 50580

accaaacgca gcaatcccct ccagtcacgc cccacgaata ccgacgtttt cagcgtgtcg 50640 10

ggtagcggcg agtaacaaga tgcacgaaga tccggaaaca aattccgata catgtaccga

50700

tatgggatgc cgtaccgcaa gcgtttcaat tcatttatct tgttctcccc gtttccactt 50760

gcttccacct cggaaacaat cccttgcaga agctccaccg tttccgattt accggggcatt 50820

ccgggatcat tctccaccaa acgcagcaat cccctccagt cacgccccac gaataccgac 15

50880

gttttcagcg tgtcgggtag cggcgagtgg tcgttcacga gatcagcatc aacccccgatt 50940

ttatgaaccg ggaagatcgg gactggcatt ctacccctggt acatgaaatg tgccatttgt 51000

ggcaggagga tttcggcagg ccgagccggg gaggggatca taattcgcaa tgggctgaca 51060 20

8068

-97-

agatgatcca ggtcggactg atgccgtccg acaccgggga ggccggaggc aaaaggacag

51120

gccagagcat tacgcattat atcattccgg gagggaagtt cgaaaccggg tagccctgac

51180

gctcaaccccc tgggcgatcc ctttcctgct ctactacggt acgggtgtcg gcggtacaag 51240 5

gtacgggaag aacatcgcct taaccctccg gggcaattac accaagcggc cctacaagat

51300

catttgcagc caacgggaca gacgggagta ttattactcg atcgaccaat tctgcaaaga

51360

cctggagatc ccggcctcct actcgaatgc acagatcgac caaaaggttt taaggcctag 10

51420

catctttgat gctttcgaac gtgcgcaggc ttcttatccc tcattgatga aacgttgccg 51480

tgccttcgac caacaactga tggctgatgc agaaaaagcc ggaggcagga aatatgccga

51540

actactcgca ttgacttacc gccactccat taccgcccat aaactcctta ccgacaagga 15

51600

aggcaacctg cttttcttat ccaaagagaa ccatagtaac ggctgtatca acacagtaga

51660

cctaacttat ccaaactatt tcctgcccga tatgtcgagc atacggccgg acactatcta 51720

tctgaatgag gtgtcgcaaa cgcacctgat cgcaccggaa aaggtgattt atatagatta 20

51780

8068

-98-

cggcgatacc tgcatacagg aaagcaaggc cgagaatacc gagaatatcg tgcgaatgat

51840

cgcagccacg ggaaaggtgg aggaatttcc caggcagaca aacgtgtcgc tggcgaccga

51900

aggggggaag ttctacacgt tcaacgtgaa ctctcgttgg gaccctttat cccgaagtta 51960 5

cagggtcaat ttgcctagtt ccttaaccgt gaatcactca agcgccttag tatattcaac 52020

ccgactacgt gtgtccgttt gcggtacggg tacctcaagg attaagttta gcggattttc 52080

ttgggagtat gcttacacgc actattggat tgttccgaag aacgctccat actatcaggt 52140

tcgactctca tcccggattt gcctgggatg atcaacatct acaaacgaca agaagacaaa 52200 10

agaggcacgt gaaaaacagg aaaagatgga aaaactcctc aaacgtgcgg aggaggcgtt

52260

cacggcagga agatactcgg aagcgacaac ctgcttcagg caggccaagg tactcgcaga

52320

tacggacagg cagaaacaga tagaggcaag gatacaggaa gtgcagaagg agtcgtcaca 15

52380

gggctgcctg tttcctgaaa cggacacaca gccgcttcca caacagccgc ccgcaaacaa

52440

cgacaagaag acaaaagagg cacgtgaaaa acaggaaaag atggaaaaac tcctcaaacg 52500 20

8068

-99-

tgcggaggag gcgttcacgg caggaagata ctcggaagcg acaacctgct tcaggcaggc

52560

caagggactc gcagatacgg acaggcagaa acagatagag gcaaggatac aggaagtgca

52620

gaaggagtcg tcacaggggct gcctgtttcc tgaaacggac acacagccgc ttccacaaca 5

52680

gccgcccgca aacaacgagg ccggacggga gcttatctta gcccacctta tcaaaaggcca

52740

aaaggagaaa ttcgattata tcctgatcga ctgtcctccc tcgctgtcgc tgctcacgct 52800

taacgcactg acggcctcgg ctcggttgat tatcccggtt caggctcaat tcctggcaat 52860 10

gcgtggaatg gccaaactta tgcaggtagt ccacaaggtg cagcaacgtt tgaactcgga

52920

tctttcgatc gccggggttc tgataacctg ggggaaataa tggtccgtcc aatctgttta 52980

acgcaatgat ttctccttta atccctttga gtataaaggg agtcatctgg tatcaggggag 53040

aatttaactc cggcggctct ggaaaagaat atgctaccct gttctcccgg atgattacgg 53100 15

attggagaga gaaatgggga atcggtgatt ttcctttcgt atatgtgcag cttcccaatt 53160

tcgaaccggt agatcccgag ccgtctgtcg aaggaaacgg ctgtgacgga agtaagcacg

53220

gcagcggaac ttctgaatgg agaaaacgta ttctggtacg aagaaaccccc caatctgaat

53280 20

8068

-100-

aagtttgcaa ccaaaggaag tgaatttgag aaagtggtta tcacaaagaa tccgctgttg

53340

cacatcaaac tgggcagcac cgacatcacc gccaatcgta tcgagctgga cgtggaaggt

53400

ttccgctttg agccggccga ccggaacttg gtaagcaacg gaaccctgtc tgcaccgcaa 5

53460

tacgcaactc ttatacgtgc ttccggccaa cgagatcgtt tacgaccaga cggtagaggc

53520

gttccatatc aagaaccgga gccacgtaaa cctgatgaag tcgatccgta acgacttttc 53580 10

agggggacgg ccgtattcgg agatattcat ccggtttatg gatagttatg caacggtggt 53640

acgcctggag ctttcaccgg aaaaattgct tgcattccag accgacggcg agaaatggaa

53700

caaattgcag gagaatccca atgccgcag acgttcgtag gttttcttct ccctgttact 53760

ctgcacacaa acaaccaacc aacacttttt ttcatccata ataactcctc caattctatc 53820 15

atttaaagtc acaataaggt accctccaag cgcgctccgc tcccgccagt cacatacatg

53880

acggctacct gaaaaatttt atgtcttatc tatctaactt ttttccttct tttctatcct 53940

gtaaaaagga aaaagcctag tttatcaaaa tcccaatgcc gacagacgtt cgtaggtttt 54000 20

cttctccctg ttactctgca cacaaacaac caaccaacac tttttttcat ccataataac 54060

8068

-101-

tcctccaatt ctatcattta aagtcacaat aaggtcccct ccaagcgcgc tccgctcccg 54120

ccagtcacat acatgacggc tacctgaaaa attttatgtc ttatctatct aacttttttc 54180

cttcttttct atcctgtaaa aaggaaaaag cctagtttat caaaatctac cggatttgtt 54240

tccatggaga atatgcttgc cgcctgttcc aatgggcttc ccgattccgc cttgtgcgaa 54300

tggtgctgcc atagttcggt gccggtatgt gcggaacgtt ctgtggcagg tataccgtcc 54360 5

caccatttga aaagttcatt gtaaatgttt gcggaaaatt ccttgcccat gcgcgaaccg 54420

ttaaatactt cccgcctgtt atggtcgatg aacgtgacac cgtagatacg tccctgctaa 54480

tctaccggat ttgtttccat ggagaatatg cttgccgcct gttccaatgg gcttcccgat 54540

tccgccttgt gcgaatggtg ctgccatagt tcggtgccgg tatgtgcgga acgttctgtg 54600

gcagggatac cgtcccacca tttgaaaagt tcattgtaaa tgtttgcgga aaattccttg 54660 10

cccatgcgcg aaccgttaaa tacttcccgc ctgttatggt cgatgaacgt gacaccgtag

54720

atacgtccct gctctgaaag gaaacaaatc gcacgatgcg ttcgtggccg aaatgttact

54780

ctattttgaa acaacgggga tcaccccgca gtcgaatgta atgccgccga acattgcggc 15

54840

caaagagcag gcaagccggg tgatcgaagt tgtccggggc attgagaaat ccactaacgt

54900

aaggctgaaa aacatcgaac aactcctttt gtcgcttgtc ggggaagtga aaacgccggg 54960 20

8068

-102-

ggacaatccg gacgaatata tgcacatcaa ttctccttga ctttcgactg gtttatagat 55020

aaacgttatg atcagctagt taccagaaat gatattccgg atatattagg tatcggcttg 55080

tctcctgaaa atgtagcaga aactaccaat aaaggttttg atggacagat tggttatcaa 55140

gaccgttttg gtaacttcaa ttttaatacc aattttgtat ttggttatgc taaaaatcga 55200

gtcgattata aagctgaggc tcaacagaaa tatgaatggt tgaaattctc cttgactttc 55260 5

gactggttta tagataaacg ttatgatcag ctagttacca gaaatgatat tccggatata 55320

ttaggtatcg gcttgtctcc tgaaaatgta gcagaaacta ccaataaagg gtttgatgga 55380

cagattggtt atcaagaccg ttttggtaac ttcaatttta ataccaattt tgtatttggt 55440

tatgctaaaa atcgagtcga ttataaagct gaggctcaac agaaatatga atggttgaaa 55500 10

tgagccgtac aaggtggctt tcacttccac cctgacgatt tacggcgttt cggggcagaa 55560

gctaaggttt ctttatcagga cgaaagggga gatcgtgag a accacgccgc aatttccgga

55620

gaacgagacg ggatttttct ttaaccagtt tatacagcag attgtccgga tagaacaaga 55680

acctgaaaaa aagtaacact atggataagg ccacgaaaac aaaaataatc ctgttcgcat 15

55740

ccctggggat cttaatgagc cgtacaaggt ggctttcact tccaccctga cgatttacgg 55800

cgtttcgggg cagaagctaa ggtttcttat caggacgaaa ggggagatcg tgagaaccac

55860

gccgcaattt ccggagaacg cgacgggatt tttctttaac cagtttatac agcagattgt 55920 20

8068

-103-

ccggatagaa caagaacctg aaaaaaagta acactatgga taaggccacg aaaacaaaaa

55980

taatcctgtt cgcatccctg gggatctttc gctcaccgaa atgtttgaaa tatccgacta 56040

tgcggaatca tgccgtttca gcgattgtaa acatatcgac gagccgggtt gtgctgtttt 56100

agaggcggta cataatggta cgttagatca taagggatat gagagttatc tgaaactcag 5

56160

acgagaagca tggcacttct ccgcttccga acatgaaaaa cgtaaaaagg agaaatcctt

56220

tacgaaactc gtagaagaag tgaagaaacg caaggctaat ttcaatggga acgtgacgga 56280 10

aaagaatacg gctggggaaa caaccgcgga ctcgtactga tgaaatcgtg ggacctgatc

56340

aactggaaac gtaccaatgc ccgtttcgac ctgttatcgg caggcttggg tgaaatcggc

56400

tgcgtatggg cgcccgaagt gacttacgat gacaagaaag gtaaactgat gatttacttc 15

56460

accatgcgtt tcaagaacga ggcgaacaaa ctgtactatg tctatgtcaa tgatgactaa

56520

tgggaacgtg acggaaaaga atacggctgg ggaaacaacc gcggactcgt actgatgaaa 56580 20

tcgtgggacc tgatcaactg gaaacgtacc aatgcccgtt tcgacctgtt atcggcaggc

56640

8068

-104-

ttgggggaaa tcggctgcgt atgggcgccc gaagtgactt acgatgacaa gaaaggtaaa

56700

ctgatgattt acttcaccat gcgtttcaag aacgaggcga acaaactgta ctatgtctat 56760

gtcaatgatg actaagcatg agcgatataa ccggggaaat caggttttcg atctgatagg 568205

cgttcgatac gacaaccaat ttcggacatt ccggatctat caggttaaag tcgaaatcat 56880

ttccggaaag gacataacac tccttttttt cgttggcgag cgtgcttaga ctgttggtaa 56940

ggctgcttag atagctgctt tgcgtcttgg ggctgtcctt tgcgtccagg aatgccccgg 57000

ccagtacccg gctctggtgc ttgccctcaa gcatgagcga tataaccggg gaaatcaggt 5706010

tttcgatctg ataggcgttc gatacgacaa ccaatttcgg acattccgga tctatcaggt 57120

taaagtcgaa atcatttccg gaaaggacat aacacgcctt tttttcgttg gcgagcgtgc 57180

ttagactgtt ggtaaggctg cttagatagc tgctttgcgt cttggggctg tcctttgcgt 57240

ccaggaatgc cccggccagt acccggctct ggtgcttgcc ctcacaaaag acaactaaca 5730015

taggaataag aataacaaaa gtaaacctat ttagatatta aagtatattg agtaaactaa

57360

ttcagttata acaaacgaag ttgtcaacta aaaccagtac acatcagtct atacagagct

57420

ttttagtttc tcccgcttga aacttttgtt tctcctgctt ggaactaaag tttcatcggc 57480 20

8068

-105-

ttgaaacttt agtttcaaag ccgtgaaacc aaagttccgg acgcttgaaa acagtggtac 57540

aatggtaaac cgctggttac ggtttgggga gtcggattta atgataatcg tcgctatggg 57600

ctgaaagaag ccgctcatat tattgacggc ttgaagtcac agggattcag tgtgatgctt 57660

ggagtaccta cgcagtggcg tacactgaat ggggacacag aatcagatcc ccgcctgcat 5 57720

gagcttatcc gaaaatgtga tatcatgatg ccttggtttg tagggcgtta taatgaaacg 57780

acttatccca agtacaatgg taaaccgctg gttacggttt ggggagtcgg atttaatgat 57840

aatcgtcgct atgggctgaa agaagccgct catattattg acggcttgaa gtcacaggga 57900 10

ttcagtgtga tgcttggagt ccctacgcag tggcgtacac tgaatgggga cacagaatca

57960

gatccccgcc tgcatgagct tatccgaaaa tgtgatatca tgatgccttg gtttgtaggg 58020

cgttataatg aaacgactta tcccaagtac aaggcgttcg gtctgctctt cgttgctcca 58080

tgcgggttct cccatatccg tccagaagcc ggagatgcca tcgtcaatgg gtttctgctg 58140 15

ataggttccc caccagtcgg ctacggcagg taaggtaaaa tccactaccc cacaatttcc

58200

gccccaaggc cacggcatgt cataactctt cccgttcgtg ctgtccttga caaaatatcc 58260

cagacggtcc gcttcctccc attgcttctt gttggcttgc gagacaaggc gttcggtctg 58320

ctcttcgttg ctccatgcgg gttctcccat atccgtccag aagccggaga tgccatcgtc 58380 20

8068

-106-

aatgggtttc tgctgatagg ttccccacca gtcggctacg gcaggtaagg gaaaatccac

58440

taccccacaa tttccgcccc aaggccacgg catgtcataa ctcttcccgt tcgtgctgtc 58500

cttgacaaaa tatcccagac ggtccgcttc ctcccattgc ttcttgttgg cttgcgagga 58560

aagccgacac gattatcctg ttcatccatg cgagaaatcc ccaagaactg cgaggcgacc 5

58620

agcaacaaca atactcgttc gtttaccgtt gggtttacgg tgctttaagc tatccgagcg 58680

acaacaccccc ggtaagggca ctcgacaaga tcctggaaag cggacggctg aaagacgtgt

58740

acgaccgttg tgcatattac gacgataagg tttgcagcgg tgaaatgagt acagcccacg 10

58800

cacaaaattc actcaacttc ttcgtcttaa ttctcacact actcagccgg aacttgacag 58860

aacgaatctg atcgctttgc aagctactct gaaaggtgat gcaattgatc aagatgagaa

58920

aaatgccgtc attacttctc tgtatgtagc tgtatatgat aatattttgg ctgctgaaga 58980 15

tgttcgtatc gctgataagg aaactttgtt tgaaggtggt aatgctgctc attatgcaac 59040

tacattcgat gcttgtacga aagaagaatc aagatgacat tgacggtaga cgaaaacggc

59100

aaaccgtttt ataatgtgtc ggtggatgac tccctcttga tagaaaattc agccatggggc 59160

tttacggcgg ctaacggcat cattctggca gaaggttttc aggtgaagaa cacgactttc 59220 20

8068

-107-

agcagtgaag acgaaacttg gacacagccg tggggagaga ataaaaagaa ccggaatcat

59280

tataacgaaa tggcagtcag cctgacaaat gaagatcagg tacacagatt attgatgttg

59340

tttccaatgc gatagacgga aaccgtatcg acgaggattt tataaagagt tgtatttacg 59400 5

gcaaagtgaa tgcggaactg tatgcgcatc ttttaggcaa atacaggggg tatgacgggg

59460

atttctttca gttttatttg gggacggacg atcggataaa ccgggctttg ctggagaacc 59520

tggggattaa ggtcgaaccc gacaaatatc cggactatga tagccggatt gttgcgcaac 59580 10

agattattga tgttgtttcc aatgcgatag acggaaaccg tatcgacgag gattttataa 59640

agagttgtat ttacggcaaa gtgaatgcgg aactgtatgc gcatctttta ggcaaataca 59700

gggggcatga cggggatttc tttcagtttt atttggggac ggacgatcgg ataaaccggg

59760

ctttgctgga gaacctgggg attaaggtcg aacccgacaa atatccggac tatgatagcc 15

59820

ggattgttgc gcaacagtac tggttcgcta tcggtctctc ggggagtattt agccttaccg 59880

gatggtcccg gcagattcac gcaagatttc tcgtgtcccg cgctactcag gataccacta

59940

cgcttaattt gacttcgtat cccggactat caccgtctat ggttcaactt tccagaggat 60000 20

tctactcatc aaatgtcttg cgacatcgtg gtcctacaac cccacacatg ccgtaacatg 60060

8068

-108-

ggtggtttgg gctattcccc gttcgctcac caaggggagt tagaagaaga aaagaaaaca

60120

gttgaggttt ctgaagccat tacagagact ccgactgaag aaggtaccga aaaagttact

60180

gaagaagtta ctgccgaagt tcagactgaa gcagcaccta aacctgccac aaaggaagac 5

60240

gtactgaacc gattgaaaga gcttgcgcaa gactcggaaa acgcaaacaa gcaggaaatt

60300

gacaatctaa aacaatcatt ctacaagtta cacaacgccg agtaccaagg ggagttagaa 60360 10

gaagaaaaga aaacagttga ggtttctgaa gccattacag agactccgac tgaagaaggt

60420

accgaaaaag ttactgaaga agttactgcc gaagttcaga ctgaagcagc ccctaaacct

60480

gccacaaagg aagacgtact gaaccgattg aaagagcttg cgcaagactc ggaaaacgca 15

60540

aacaagcagg aaattgacaa tctaaaacaa tcattctaca agttacacaa cgccgagtac

60600

catctgatcg aactgggcgt gacacacgtg catctgcttc cttcttttga ttacgcttcg 60660

gtagatgaaa ccagactgaa tgaaaattcg tacaactggg gatatgatcc gcaaaactat 20

60720

8068

-109-

aatgtacccg atggttccta tgccactgat ccctatcagc ccgccactcg tgtgaaagaa

60780

ttcaagcaga tggtacaggc actgcacaaa gctggtatcc gtgtgataat ggatgtggtg

60840

tacaatcata cataccatct gatcgaactg ggcgtgacac acgtgcatct gcttccttct 60900 5

tttgattacg cttcggtaga tgaaaccaga ctgaatgaaa attcgtacaa ctggggatat 60960

gatccgcaaa actataatgt ccccgatggt tcctatgcca ctgatcccta tcagcccgcc 61020

actcgtgtga aagaattcaa gcagatggta caggcactgc acaaagctgg tatccgtgtg

61080

ataatggatg tggtgtacaa tcatacattc gacctgcggg tgcatggtac agaactggat 61140 10

gccttcatgc gtgcccacgg gcttaccgcg caggaacaga gcgagatgct ccgttcagtg

61200

acgggtgagg acatctctcc gacttatgtg gcggggggaa aggtgcaaca acatgtgcgc

61260

tatctgccgg aaatgaaaag acaaataacag acagaaacgg acaggctgtt cgtaagcccg 15

61320

cgtacaaggc ctgtgagtgt gataaggaaa gagtttccgg actacctggg cgaaagaact

61380

taaacaggca tacgaacagt ttcaagtgct gggggaatcc agggacatac tgactaagag

61440 20

8068

-110-

cctggatctg taccggcagg tgaacggggt tatcaaaaac tctaaaatgg ggttgcaggt

61500

gctttccatg cagggggaaa tgttggaact ggcggcgaaa gagtgcaccc ggtcggacgt

61560

gtttaccgga caggaggcat acggggaata tacgaacgtg ctgaacaaga tcatggagac 5

61620

cgatcccggt agcggcggac gtcatatgtc gaatcacttc gccaaaccgg aatggcatat

61680

tgaaaatata tcttctgcta ccggaacgca tgacctgcat gcggcgggtg tagcaagagc 61740 10

aatggtatat tatggggcata aagggagtagc aatcacttcg cacggagaat ctgctacttc 61800

cgaaggcttt gtttacgagg ctatcaatgg agctagtctg gaacgtcttc cagtgatttt 61860

cgttatacag gataccgatc ccggtagcgg cggacgtcat atgtcgaatc acttcgccaa

61920

accggaatgg catattgaaa atatatcttc tgctaccgga acgcatgacc tgcatgcggc 15

61980

gggtgtagca agagcaatgg gatattatgg gcataaagga gtagcaatca cttcgcacgg

62040

agaatctgct acttccgaag gctttgttta cgaggctatc aatggagcta gtctggaacg 62100

tcttccagtg attttcgtta tacaggatac cgcaggggat tacggggaca tcgccccggt 62160 20

gtgggggatc gtccaaaagg acggggatat ttaccgtttc gtcccctctg tcgcacccct 62220

8068

-111-

gaaagagaaa taccggatct ccgaccgtta cggctcccgg acgcatccga taagcggtga

62280

aaggcagttt cacgcaggcc tggatatggc ggcggtgtat gcggctaccg tacacgccgc

62340

agccagtggg acggtgacgt tcgcaggtga aacgcccgga tatctcctgc aatttgttcc 5

62400

atttctcgcc gtcggtctgg aatgcaagca atttttccgg tgaaagctcc aggcgtacca 62460

ccgttgcata actatccata aaccggatga atatctccga atacggccgt acccctgaaa

62520

agtcgttacg gatcgacttc atcaggttta cgtggctccg gttcttgata tggaacgcct 62580 10

ctaccgtctg gtcgtaaacg atctcgttgg ccggaagcac gtataagagt tgcgtattac 62640

cggcaccttc tcggtggagg gcgaccgcat caccctgctg gaggccatcg ccaaggcggg

62700

cgatgtcacc caaaaggggcc gggtgaaccg tgtggcggtc atccgtgagg aggacgggca

62760 15

gcgggtgatg taccagcacg acctgcgcag caagggagctg ttcgagtcgc cctgcttcta

62820

cctgcaacag aacgacatcg tctatgtcga accgaaatac cgcaagcagg accgcgagga

62880

caagggctgg aagaccggca ccttctcggt ggagggcgac cgcatcaccc tgctggaggc 20

62940

8068

-112-

catcgccaag gcgggcgatg tcacccaaag gggccgggtg aaccgtgtgg cggtcatccg

63000

tgaggaggac gggcagcggg ggatgtacca gcacgacctg cgcagcaagg agctgttcga

63060

gtcgccctgc ttctacctgc aacagaacga catcgtctat gtcgaaccga aataccgcaa 5

63120

gcaggaccgc gaggacaagg gctggaagca ctacggtaaa tgcgtgtgga aatgctaaat

63180

cagacgaact ccaacttccc gttccatcgg ctgccgcagg caatgtgaag gcgccggcaa 63240 10

atttgaaatt atgaatcttg atcacgtcga tgtccacctg catgttatcg tattgggtct 63300

ttgctttgaa tacgacctgt gacagaatat gtttgaaatt aaatttcact attccgttgt 63360

tcatgtcttt tgtctggcct ttggccatgg catacatcac gtcactctta ttgccagcgc 63420

cgtaaggtag gagcgttgat cgtcaaagac aaaatgatta tctccgacgg atacaatggt 63480 15

actccttcgg gcttcgaaaa cgtatgcgag gacgagaata acctgacaaa accttatgtt

63540

ctccatgcgg aagcaaacgc tatcaccaag atagcacgct cgaacaacag cagcgacggt

63600

gccacgatgt acgtcaccgc ctcaccttgt atcgaatgtg caaagttaat catacaggac 20

63660

8068

-113-

tcttattgcc agcgccgtaa ggtaggagcg ttgatcgtca aagacaaaat gattatctcc 63720

gacggataca atggtactcc ttcgggcttc gaaaacgtat gcgaggacga gaataacctg

63780

acaaaccctt atgttctcca tgcggaagca aacgctatca ccaagatagc acgctcgaac 63840 5

aacagcagcg acggtgccac gatgtacgtc accgcctcac cttgtatcga atgtgcaaag

63900

ttaatcatac aggactttgc cacggtgcgg gtagtattcg actggaccaa gatttccaat 63960

catgacaagc ctgaaggcat gagggtcgta ttttatccga ccgatgatga aagcaacacg 64020 10

tggatatttg atttccccgg cggagaggat ggggaagtgg agctccccga gaatgattac

64080

cgggtaattt gcttcaacta cgataccgac gggatggttt ggaaagaaaa cggcagttac

64140

acgcttttta ctgccgatac gcgtgatgac tgatactcat caatgataaa gtcttttctt 64200 15

ataatgggca catcgaccaa aggacgtgct gtacgaatat ctttcagact tcctccaaaa

64260

aacttctcat cagtgagaat agagaggggcg gaagcacctg ccgcaaggta tgacggaaca

64320

atttcttcgg gacgtgcctc ctgtttgatc caccctttgg atggcgagcg acgcttaaat 64380 20

8068

-114-

tcggctataa taccggaatc ggaagaagcc aatgcccgtt tcaactgata ctcatcaatg 64440

ataaagtctt ttcttataat gggcacatcg accaaaggac gtgctgtacg aatatctttc 64500

agacttcctc caaaaaactt ctcatcagtg agaatagaga gggcggaagc ccctgccgca 64560 5

aggtatgacg gaacaatttc ttcgggacgt gcctcctgtt tgatccaccc tttggatggc 64620

gagcgacgct taaattcggc tataataccg gaatcggaag aagccaatgc ccgtttcaga

64680

gggcaagcac cagagccggg tactggccgg ggcattcctg gacgcaaagg acagccccaa 64740 10

gacgcaaagc agctatctaa gcagccttac caacagtcta agcacgctcg ccaacgaaaa

64800

aaaggtgtgt tatgtccttt ccggaaatga tttcgacttt aacctgatag atccggaatg 64860

tccgaaattg gttgtcgtat cgaacgccta tcagatcgaa aacctgattt ccccggttat 64920

atcgctcatg cttactgggt ggtgaccata tgctgtgcaa agaatatttc ccgaacgaca 64980 15

acctgacgat gagcgaggaa ctgaaaacgg caatggttca ctactacgac ttcctcacgt

65040

cttatcagaa cctgctccgc gatggcggaa cggagaacag catcgctatg aactgtacca

65100

acggagaaat gaaactcaac gtatggcctc caaagttggg gtcggtcact acttacgcca 20

65160

8068

-115-

agcaggtaga cggcaagcaa gtagtgcaac tgggtggtga ccatatgctg tgcaaagaat

65220

atttcccgaa cgacaacctg acgatgagcg aggaactgaa aacggcaatg gttcactact

65280

acgacttcct cacgtcttat cagaacctgc tccgcaatgg cggaacggag aacagcatcg 5

65340

ctatgaactg taccaacgga gaaatgaaac tcaacgtatg gcctccaaag ttggggtcgg

65400

tcactactta cgccaagcag gtagacggca agcaagtagt gcatcgctca ccgaaatgtt 65460 10

tgaaatatcc gactatgcgg aatcatgccg tttcagcgat tgtaaacata tcgacgagcc

65520

gggttgtgct gttttagagg cggtacataa tggtacgtta gatcataagg tatatgagag 65580

ttatctgaaa ctcagacgag aagcatggca cttctccgct tccgaacatg aaaaacgtaa 65640 15

aaaggagaaa tcctttacga aactcgtaga agaagtgaag aaacgcaagg ctaatttccc

65700

gataagcggt gaaaggcagt ttcacgcagg cctggatatg gcggcggtgt atgcggctac

65760

cgtacacgcc gcagccagtg ggacggtgac gttcgcaggt gaaacgcccg gatatgggaa 20

65820

8068

-116-

aacgggagtc gttacgcacc gtttcggatt tcagaccaga tacgcacatc tgacactcat

65880

ttacacccgg aaaggtgcga aggtggaaaa gggggacgtg atcgggttcg tgggaagcac

65940

cgggataagt accatatact aaatgctcca cgctatgatg acgacaggac tctaagatgt 5 66000

tataaaatcc aataagatta ctttcaatat aggcatcagg gttagtgatg ctatagcgta 66060

caccggcttg tgcagcaagg gtcacgacta cctgaggatg gtagttagtg aaaatagact

66120

caacaatttc ctttttagca atactgtctt ttatgaaaac aaatctgtca ccgtaagcag 6618010

acaattcttg taagcgttca tactttaaat atcgaggacg tgcaaaggcg gcataactgg 66240

gtagggcagc agattcagga ggttatcatg ctgccgttca atattgcggc ttatacgata 66300

ctcctgtacg caacgaaata tatatttttc ttcttggcgt cagcccggta tctgtatctt 66360

atactcctgg agatcgtcac gccgatagcc gtaatactct acatggacga gaaaacgagg 6642015

cattatacgc acgcatacct gaaaaacctg tttgtctgtt acaatatgcg tgtatatcca 66480

aaacttgaac ctggaaacat tacggccgga caagacggta aaccccttgt cctctctgat

66540

tactacccta ttgggggaac tggccgcaat cgaacgccag gggatcattg gccgccttaa 6660020

8068

-117-

tagcggacgg gagttgtaca tccagaaagg gggcaggctg ggacggaagc cgggaagccg

66660

gaaaacggcc gaacagagga aagaggaata ccgggaggcg atcgccttgt tgaagaaaat

66720

cagtaaatcc gatgacgcgt gcgccgaggc gattggctgc tgtttcgaaa ctcaaacggg 5

66780

tacgggtgga aggttcgaag aacagggttg ctactacctt accttgcaat aaccggcggt

66840

tggggttcat ttcaaactgc ttcgccattt cgagcatgta gaggattttt tctttagaat 66900

gttcggcaat ggttactaaa cttctgtttt ccattttgtt atcttttatg tggatagaac 66960 10

ttgttttacc ggaatcagta aatccgatga cgcgtgcgcc gaggcgattg gctgctgttt 67020

cgaaactcaa accggtacgg gtggaaggtt cgaagaacag ggttgctact accttacctt

67080

gcaataaccg gcggttgggg gtcatttcaa actgcttcgc catttcgagc atgtagagga 67140 15

ttttttcttt agaatgttcg gcaatggtta ctaaacttct gttttccatt ttgttatctt 67200

ttatgtggat agaacttgtt ttaacggaat ccaggcagga gggaacgacg ctaaggccgt

67260

ccttatgctc gtagatcggc aggtcgtatt cgcctttcat cgcaccgtag atcgtttggg 67320

gaagctccgc agagaagccc agcgattcgg tcagggtggc ctgcccgtca aggtcgatca 20

67380

8068

-118-

aaagaacctt gtaccctttt tgacgtaacg caccgcccag gttgatcgtg gttgtggtct 67440

ttcctactcc ccccttgtga ttcaatacgg agattacttt tgcatcctgt tgtatagcca 67500

ggcggccacg gtgcgggcat tgatgccgct gggcatcgcg ttaggtattt ctccgtatat 67560

gctgattgcc ttattccccg cagtgaacgg atatttcttt atcccgaatt acccgactgt 67620

cgtagccgcc attaatttcg accgcaccgg gacaacaaaa atcggtaaat atgtgttgaa 5

67680

tcattcgttt atgatgcccg gactggtatc taccgtagtc gctattgttt taggactgat 67740

cctgttgtat agccaggcgg ccacggtgcg ggcattgatg ccgctgggca tcgcgttagg

67800

tatttctccg tatatgctga ttgccttatt ccccgcagtg aacggatatt tctttatccc 67860 10

gaattccccg actgtcgtag ccgccattaa tttcgaccgc accgggacaa caaaaatcgg

67920

taaatatgtg ttgaatcatt cgtttatgat gcccggactg gtatctaccg tagtcgctat 67980

tgttttagga ctgatctcca ggtctttgca gaattggtcg atcgagtaat aatactcccg 68040

tctgtcccgt tggctgcaaa tgatcttgta gagccgcttg gtgtaattgc cccggagggt 68100 15

taaggcgatg ttcttcccgt gccttgtacc gccgacaccc gtaccgtagt agagcaggaa

68160

agggatcgcc caggggttga gcgtcaggggc tacccggttt gtgcctttga tgttgtgtac 68220

cgtcgttatc accaccccga acgtttccag ttcagaatat cttttcgttg gatgaatatt 68280

8068

-119-

acatccgaag cggccatgta gtaaggcagg tcgcagttgt ctataggttc gtcgctggct

68340

ccggcgtgca ttctgcgcag gcggttgagc aaggggataa gcaggtaata tcctgcccgg

68400

gatgtccagc gcttgaagaa gttgctgcca tacctgttga atctcgaaaa cgggtacagc 5

68460

cgtggagcaa gcaggaactt ctttgcttca tcccattttc ggaatcgtcg catcgacggg 68520

tgggggaaag tcggttacgt cgttgaacat catccagcag aacatcgagc agaattataa

68580

acagatcgtc gtcgagttcg gaaagagctt ttaccagctt tcgcagttgt gcccggacag 68640 10

gtcgctgcat attgattatg acggcagcag cccgttgggg atcaatccgt tctatacggc 68700

cgggaagcag ccggacaacg agaagataaa gacgcttgta aacctggtgc ttaaattcat

68760

tacgacttgt cccggcatcg aaaggctggt ctttttatca cctttcaaaa gctcgaaatc 68820

gaaaagacgg aaaaagcccg gatcggcata agctatctgg ttttcccgca gtgtcaactc 15

68880

accatacttc acaatctgtt caggttggag cagagagccg attcgggtat aatcttcaat 68940

tcccgcaaga ttctctttca ttgccgagcc gtatccgaaa gagctgcttg cccagttatc 69000

ggtcagcacc tccattacga cttgtcccgg catcgaaagg ctggtctttt tatcaccttt 69060

caaaagctcg aaatcgaaaa gacggaaaaa gcccggatcg gcataagcta tctggttttc 20

69120

8068

-120-

ccgcagtgtc aactcaccat ccttcacaat ctgttcaggt tggagcagag agccgattcg

69180

ggtataatct tcaattcccg caagattctc tttcattgcc gagccgtatc cgaaagagct 69240

gcttgcccag ttatcggtca gcacctccat tatatagaaa gaaatgtaag gccggcgaag 69300 5

caaacagttc tactccctgt gatgctagtt ctttggcacg aagcaacgtg ctgataagca 69360 ttcgttcata ggctaccgat gtcttgtgca aatatacctg ccaatacatg aggcgacgtg 69420

ctgtcaggaa attttcgata gagtagatac ctttggattc aattacgaga cggtcgtcgg 69480

ccacatcaag catcttgatg atgcgggcag aaccgatatt cccattatat agaaagaaat 69540 10

gtaaggccgg cgaagcaaac agttctactc cctgtgatgc tagttctttg gcacgaagca

69600

acgtgctgat aagcattcgt tcataggcta ccgatgtctt gtgcaaatat ccctgccaat 69660

acatgaggcg acgtgctgtc aggaaatttt cgatagagta gatacctttg gattcaatta 69720

cgagacggtc gtcggccaca tcaagcatct tgatgatgcg ggcagaaccg atattcccgc 15

69780

cctcactcct gtgatagaac taatgcgcat tcggagttta tcaagacttg ataggcggtg 69840

aagccctcgc atcttatcag tcgctctacc tcacattagt aactcacaag gctgcaccta 69900

aatgcatttc ggggagtacg agctatctcc aagtttgatt agcctttcac ccccaccctc 69960

agttcatccg gaagcttttc aacgcttatc ggttcggtcc tccagttagt gttacctaac 70020 20

8068

-121-

cttcaacctg accattcggc tgttatgccg aatttgatac taccgatcat ccggaagtta 70080

tggtacgttc cggaatatct tatgtagata tggcaggggc ttccaacaat ctttccaatg 70140

agataacgga accattcggg tggaattttg aagctgtaca caaacatcag tcggatagtt

70200

ggaataatat tttaaacagg gttcggatat acagcaacga ttatcgggaa aaagtaagat 5 70260

tctacaccaa tttataccgt gcgttctgat tcggctgtta tgccgaattt gatactaccg 70320

atcatccgga agttatggta cgttccggaa tatcttatgt agatatggca ggggcttcca 70380

acaatctttc caatgagata acggaaccat tcggggggaa ttttgaagct gtacacaaac 70440 10

atcagtcgga tagttggaat aatattttaa acagggttcg gatatacagc aacgattatc 70500

gggaaaaagt aagattctac accaattt accgtgcgtt ctgatttcaa acctgtattc 70560

ggcaaaaaga gccactttcg ggcttagcaa catttccggc cttatcccga cctcgtaccc

70620

atacacgaaa gccttgcttt tctccaggta cacaagatcg cttttcgcct cggctttctg 70680 15

gtagccgatc gtcccggctg cgatccccag gagcgagaat ttccgtcctt tcagggcgta

70740

ataggccagc tccggggccga ccgtcacggt gtttgccttt accagatccc ggtttagacc 70800

ttgtcctcgt acatttcaaa cctcaaatga aagttcctca tgttggaatg tgccgcactc 70860

cccacgaact cgcccgattt caggctggta aagaaattcg tgtcgtatat ttcctctttc 70920 20

8068

-122-

tgcgtggaaa ctgtacggct gcggttctcc cctccccggc tgcttccggt ggtctttgaa 70980

accctctgcc tctcctcttt tccaaaaaca agcgggtagc ttttcaaggc ctctatgtcc 71040

tttgtccggc caactgatca gctgtgggtt agtgatatca cttacattac catatggttg 71100

cctgacggca gttatgtgtt ctgctacctg tctctggtga cagacgccta tacgaaggag 71160

atcattgggt attgcgtagg tgatactctg ggaagctgtt acacagtgga agctctggaa 71220 5

atggcagtca gacgcatagc tgcaaaggag attaagggtt tgatccatca ctccgaccga

71280

ggcgtacaat atgccagtgc ggattataat tgtacagtca ctctgcagtc gtcacaaaac

71340

tataattgtg tcggtacact cattatcaag cagcagccga gaggatatat tgttgacatt 71400 10

gacgaatcaa agaaggaata tcaggtgaaa gctactggag aaacaatcac gattccattt

71460

aaagtaaatg gtcctgcaga tgcgtatact tatgaagtgg aggcttctgc ccgtgaatgg 71520

attacgcctt tgcctgccac gagaggtatg cgcgatgctt ccgattgtac agtcactctg 71580

cagtcgtcac aaaactataa ttgtgtcggt acactcatta tcaagcagca gccgagagga 15

71640

tatattgttg acattgacga atcaaagaag gaatatcagg tgaaagctac cggagaaaca

71700

atcacgattc catttaaagt aaatggtcct gcagatgcgt atacttatga agtggaggct 71760

tctgcccgtg aatggattac gcctttgcct gccacgagag gtatgcgcga tgcttccgat 71820 20

8068

-123-

gaaacaggct attcacggcg atgcaagtgc tttgagccag atacctgatg cgctgactct

71880

gtttatcgga cagaacggcg gatgtatcgg tgaagtaagt gcgctggcac tgttgctcgg

71940

actggtatac atgctctgga aaaagatcat cacctggcat attccggttt ctatcattgt 72000 5

gactgtattt gtatttgcag gcattatgca catggtggat cccgaaaagt atgtttctcc 72060

gatattgcaa ctaatgaaac aggctattca cggcgatgca agtgctttga gccagatacc

72120

tgatgcgctg actctgttta tcggacagaa cggcggatgt atcggtgaag taagtgcgct 72180

ggcactgttg ctcggactgg gatacatgct ctggaaaaag atcatcacct ggcatattcc 72240 10

ggtttctatc attgtgactg tatttgtatt tgcaggcatt atgcacatgg tggatcccga 72300

aaagtatgtt tctccgatat tgcaactaat gcccgtgtca gcccgaagaa acttttcgag 72360

gacatggaca agttcataga agccaccaaa gattttcaat tagttcttta atcctttaat 72420

acagaaaact atatgcgaag cacattttca cttttaccct acattaaccg cagcaaagta 72480

aaggctgacg gtacgaccgc catactctgc cgcataacca ttgacggcaa acagactgcc 15

72540

atcagtacgg ggatttattg ccgaccggaa gaatggaaca gcaatgcccg tgtcagcccg

72600

aagaaacttt tcgaggacat ggacaagttc atagaagcca ccaaagattt tcaattagtt 72660

ctttaatcct ttaatacaga aaactatatg cgaagcacat tttcactttt cccctacatt 72720 20

8068

-124-

aaccgcagca aagtaaaggc tgacggtacg accgccatac tctgccgcat aaccattgac

72780

ggcaaacaga ctgccatcag tacggggatt tattgccgac cggaagaatg gaacagcaat

72840

gctcaccgag ggcgatatga tcgtccggat caggtcaaag gaaagcacgc tttcctccat 5

72900

gatcttgttc agcacgttcg tatattcccc gtatgcctcc tgtccggtaa acacgtccga 72960

ccgggcgcac tctttcgccg ccagttccaa catttccccc tgcatggaaa gcacctgcaa

73020

caccatttta gagtttttga taacccccgtt cacctgccgg taacagatcca ggctcttagt 7308010

cagtatgtcc ctgatgctgc acaactatcg taacaatccc tgtgtagtga tgtggagtat 73140

cggtaatgaa gtccccacgc aatgcagccc tgtaggatat aaagtagcca agttcctgca

73200

agatatctgc caccgtgaag cccctacccg ccccgttacc tgcggcatgg accaagtgac 7326015

ttgtgttcta gccaacggat ttgctgccat gatcgatatc cccggtctga actaccgcgc 73320

caatcgctat caggaggcat atgacaaaat gcgctacaaa cgctaaagca actgatgccc

73380

cgcaacgtaa tggcaggcgt agcaacgtcc gaccattcac aatggagtct cccatctgtc 7344020

8068

-125-

gagattgaag atgctccccg tttcgaatgg agaggtttta tgctggacga aggcagacat

73500

ttcttcggta aagatgagat aaaacgagtg atcgacatga tggccatcta caaaatgaat

73560

cgtttccact ggcatctgac agaagatcaa ggctggagaa tcgatgcgct acaaacgcta 5

73620

aagcaactga tgccccgcaa cgtaatggca ggcgtagcaa cgtccgacca ttcacaatgg

73680

agtctcccat ctgtcgagat tgaagatgct ccccgtttcg aatggagagg gtttatgctg 73740

gacgaaggca gacatttctt cggtaaagat gagataaaac gagtgatcga catgatggcc 10

73800

atctacaaaa tgaatcgttt ccactggcat ctgacagaag atcaaggctg gagaatcgat

73860

ggaagctaac gcagggaact gaaacatctt agtacctgta ggaaaagaaa ataataatga

73920 15

ttcccctagt agtggcgagc gaacggggaa tagcccaaac cacccatgtt acggcatgtg

73980

tggggggtgta ggaccacgat gtcgcaagac atttgatgag tagaatcctc tggaaagttg

74040

aaccatagac ggtgatagtc cggtatacga agtcaaatta agcgtagtgg tatcctgagt 20

74100

agcgcgggac acgagacatc atggcggatc tcagtacttt gttctgtggc ttccatccga 74160

8068

-126-

agcgtgtgtt caacggctat ctttttggtg gagtaggact gaaccgtggt tttgacaatg 74220

acgaagcaaa tgcgctcgat acccgtactt atgagatgga atatctctgg caggaaggta

74280

agttcctcgt tgccggacgt ttcggccttg gttgcgactt tcgcctaaac gaccgcctgt 74340

ctatcaatat cgaagcgaat gccaacgcag acatcatggc ggatctcagt actttgttct 74400 5

gtggcttcca tccgaagcgt gtgttcaacg gctatctttt tggtggagta ggactgaacc 74460

gtggttttga caatgacgaa gcaaatgcgc tcgatccccg tacttatgag atggaatatc 74520

tctggcagga aggtaagttc ctcgttgccg gacgtttcgg ccttggttgc gactttcgcc 74580

taaacgaccg cctgtctatc aatatcgaag cgaatgccaa cgcagatccg agttcaaacg 74640 10

ttgctgcacc ttgtggacta cctgcataag tttggccatt ccacgcattg ccaggaattg 74700

agcctgaacc gggataatca accgatccga ggccgtcagt gcgttaagcg cgagcagcga

74760

cagcgaggga ggacagtcga tcaggatata atcgaatttc tccttttggc ctttgataag 74820

gtgggctaag ataagctccc gtccggcctc gttgattaac tccgtttcaa cggccgagag 15

74880

caccagacgt ttctgggcat atactgaaga gaaacatatc cccgatgctg ccatcaatac

74940

aaaaagaacg gatgatttct tcataattca acatgttttt catttggttt gtgattcccg 75000

ctttttcccc gatagataaa ccagtaaagc agcggtatga taaagaggct gaccgccgta 20

75060

8068

-127-

ccgatggaca tcgtgcctat catggcgata gacaacggct tttgcagttc cgatcccata 75120

tccgaggaga acaagcacca gacgtttctg ggcatatact gaagagaaac atatccccga

75180

tgctgccatc aatacaaaaa gaacggatga tttcttcata attcaacatg tttttcattt 75240

ggtttgtgat tcccgctttt cccccgatag ataaaccagt aaagcagcgg tatgataaag 75300 5

aggctgaccg ccgtaccgat ggacatcgtg cctatcatgg cgatagacaa cggcttttgc

75360

agttccgatc ccatatccga ggagaacaag catctttgat gctttcgaac gtgcgcaggc

75420

ttcttatccc tcattgatga aacgttgccg tgccttcgac caacaactga tggctgatgc 75480 10

agaaaaagcc ggaggcagga aatatgccga actacccgca ttgacttacc gccactccat

75540

taccgcccat aaactcctta ccgacaagga aggcaacctg cttttcttat ccaaagagaa

75600

ccatagtaac ggctgtatca acacagtaga cctaacttat ccaagctctg catatcgacg 15

75660

aactgcgagc gaagcggcac tacgatataa tcggctaaag gagaatagaa agccctgtcg

75720

ccttgctgct cccgtatcgg gcaaaaccag cttttcgcct ccagcatggc ctctatttcg 75780

gggtgcgcct ctccggttgt cccgtcggggc tgctctgcct gtccccctct gaacttctcc 75840 20

cttaacgctt cccattcttc cggcctcacg tccgaaaaat tggtctgatc caggttaaag 75900

8068

-128-

taccgcttcc atactcatcc atgcaggtat aacttatctt ttggacatcc ttggtggctt 75960

cccaactata aaacgccatc atgtcttcac taaccgttcc gggattgaac gcgtaaaagt

76020

ccaaaccctc ggtaggccaa taacgaaggt cgctcgcatt gtcataatcc cacttaccat 76080 5

ttttgtacac gatcttcact ccgtcatgtt caaattccgt gtcgttcttt cccatgaagg 76140

cagtaccatc cgcagtccga tggattcgag gcaggaagca taaagcagtg ccatatccag

76200

acaagttccg agcttttgtg ccagtacgga atctgtcaga cggacacgct gcccgtgctc 76260 10

ttcgaagctg gcgggaatgg tgctgtaaat aatttgctgt tcggtaagag cggtgtagat 76320

ggctgccatc tgctttctca cacggtccgg attgcggctt tggtattcgt ccagtgacgg 76380

agtaccggtc cactgttcca gaatggcgag tccgatggat tcgaggcagg aagcataaag

76440

cagtgccata tccagacaag ttccgagctt ttgtgccagt acggaatctg tcagacggac 15

76500

acgctgcccg tgctcttcga agctggcggg aatggggctg taaataattt gctgttcggt 76560

aagagcggtg tagatggctg ccatctgctt tctcacacgg tccggattgc ggctttggta 76620

ttcgtccagt gacggagtac cggtccactg ttccagaatg gcgagtccgg aaactctttc 76680

cttacacac tcacaggcct tgtacgcggg cttacgaaca gcctgtccgt ttctgtctgt 76740 20

atttgtcttt tcatttccgg cagatagcgc acatgttgtt gcacctttcc acccgccaca 76800

8068

-129-

taagtcggag agatgtcctc acccgtcact gaacggagca tctcgctctg ttcctgcgcg

76860

gtaagcccgt gggcacgcat gaaggcatcc agttctgtac catgcacccg caggtcgaag

76920

ttattgatgg atgttcacgg aacaggttgc tatacttcgc aggcagccat gaagctgtac 76980 5

aaccggcaaa acgaacagtt gggcgatgca gcagaaagag cggcggtcgc tgccgaatgg

77040

ttgggtactg ccagctatcc gcaacacacg ctgacggagg catggaaacg tttcatcttc

77100

catcaattcc atgatgacct gacgggaacg agtatccccc gtgcctatga gttctcatgg 77160 10

aacgatgaac tgaagttcag aatatctttt cgttggatga atattacatc cgaagcggcc 77220

atgtagtaag gcaggtcgca gttgtctata ggttcgtcgc tggctccggc gtgcattctg 77280

cgcaggcggt tgagcaaggg tataagcagg taatatcctg cccgggatgt ccagcgcttg

77340

aagaagttgc tgccatacct gttgaatctc gaaaacgggt acagccgtgg agcaagcagg 15

77400

aacttctttg cttcatccca ttttcggaag ttctgcgaag atataggtgc ggaaccgctt 77460

ccggtgctgg cggcaggtgt accttgtcag aattccgctt gtcatggcga tttgagaggc 77520

ggtcagcaag gcggtatccc gatgagcgag atgggtgctt acattcagga tatcctcgac

77580 20

8068

-130-

ctgatagaat gggcgaacgg tgatgcaaag aaaaccaaat ggggcaagat acgtgccgaa

77640

tccggtcatc cgaagccttt caatctgaaa tatatcggca tcgagttctg cgaagatata 77700

ggtgcggaac cgcttccggt gctggcggca ggtgtacctt gtcagaattc cgcttgtcat 77760

ggcgatttga gaggcggtca gcaaggcggt atcccgatga gcgagatggg ggcttacatt 5

77820

caggatatcc tcgacctgat agaatggggcg aacggtgatg caaagaaaac caaatggggc

77880

aagatacgtg ccgaatccgg tcatccgaag cctttcaatc tgaaatatat cggcatcgag 77940 10

tgaattttgt gcgtgggctg tactcatttc accgctgcaa accttatcgt cgtaatatgc 78000

acaacggtcg tacacgtctt tcagccgtcc gctttccagg atcttgtcga gtgcccttac 78060

cggggcgttg tcgctcggat agcttaaagc accgtaaacc caacggtaaa cgaacgagta

78120

ttgttgttgc tggtcgcctc gcagttcttg gggatttctc gcatggatga acaggataat 78180 15

cgtgtcggct ttcaggaaca gttaaggcag aaccagagag ccgacagtct gaaagcggcc

78240

gcagccatga aacggagaac ggcgaaagcc cggccgaaaa aggaaacgcc gaagaaggaa 78300

gagcctgaaa ggacagtagg gcgtttcttt tcgggggaag aaccggagaa caagggaaac 20

78360

8068

-131-

acgatagagg ccattgtgtc gggcgatcag aagatcacga acgggagcgt gataaaactt

78420

gtcacgctcc aagaaatgca actgcccgag gaacctgcga ggatgccgtt gcctacctca

78480

gcaatcctcc gaaagaacct tttatttgca ttgcagattt tcagaacccg cataatatct 78540 5

gcggattcat cggcgaaaac gcaggagtac acaccgaccg gccgatcagc ggaccactgc

78600

ccgaattgcc ggacaacttt gacgtggaag actggagcaa tattccgact cccgtacaat

78660

atatctgttg cagtcaccgc cgcatgacac aggctgccca ttgaggaacc tgcgaggatg 10

78720

ccgttgccta cctcagcaat cctccgaaag aaccttttat ttgcattgca gattttcaga 78780

acccgcataa tatctgcgga ttcatcggcg aaaacgcagg agtacacacc aaccggccga

78840

tcagcggacc actgcccgaa ttgccggaca actttgacgt ggaagactgg agcaatattc 15

78900

cgactcccgt acaatatatc tgttgcagtc accgccgcat gacacaggct gcccattgag

78960

gaagcggaat tttatttgca gcttgatacg gaactttacg gggtgaaagc gtcggccagg

79020 20

ttcgtaaagg gaagcggccg ggtgtatatt tccgggtatg atgcgacaag gggcgaggggc

79080

8068

-132-

gtggcgctgg aaaaaaacaa cctggtgacg ttccggccgg atgcgaccgg gcaggcggtg

79140

atcgagttta ccgtttcaag ccgttacggt ctgccagtga aagagaatgt aacgatacaa

79200

gtaaatcaat gagaggatat tgcaggacga gcagtttacg gcggcaaacc agatcgtcgc 5

79260

agccatgagg gaacaaggtt acacgcacca ggtaaggaag ggggtgcatt ccttttcacg

79320

ggagggtgaa gtgttccagg gtgaacacag gctcttgaaa gcgttcgaac aacctctgtc

79380 10

tgacgagcag ctaaaaagca taacggaacg tttcgacttg acaaagtacg aggcgaaccc

79440

ggccgggtac aggggagaacg gtttgcagag ggaaaaccgg gagaaggccg ggaaactgca

79500

aacggatctc gaaatagccc ggcaggagaa aggaactccg gccgtcggat gcaatacgca 15

79560

caagatcctg gagatcgtgg agcgtatcga cgaggagaag aagataccga cattcaacga

79620

tacggtttat gagatagacc gtaatacgct ggatatgtgg gtgaaaaggt taaaggacga

79680 20

actaagaga taagcctatg tttgccaaag taacacccggc cgaagggata tacatccgcc

79740

8068

-133-

cgtctggcat ctatcgatgc gatgaacgaa ttgggtggtg ccatcgtatc tatcacactg 79800

gtcatgatgt ccgtgtttat tccggtaagt ttcatggggtg gtacggcagg tacgttctat 79860

cgccaattcg gtttgacaat ggctatcgct atcggtctgt ccgcattgaa cgccttgaca 79920

ctgagtccgg cattgtgtgc cgttcttctg aaaccgcata ctgatcatgg agataagaag 79980

ggatatacat ccgcccgtct ggcatctatc gatgcgatga acgaattggg tggtgccatc 80040 5

gtatctatca cactggtcat gatgtccgtg tttattccgg taagtttcat gggtggtacg 80100

gcagggacgt tctatcgcca attcggtttg acaatggcta tcgctatcgg tctgtccgca 80160

ttgaacgcct tgacactgag tccggcattg tgtgccgttc ttctgaaacc gcatactgat 80220

catggagata agaggaagga tgcggcaagg gattattcgt tcaggatggt gcaggcttcc 80280 10

tcttttgtgc cgggaaagaa tacgacggat atcgcgttgg ttatggatgc gatggacatc 80340

cttcatgagg ggcgggtcgg gtgttttttgt ctggtcgcca gtgacgggga ttataccctg 80400

ctggcacaac gtatcaggga gagtggtctg acggtcctcg gttacgggga gggaaagact

80460

ccggcggcac tggtacgttc ctgtactgat atcgaggacg tgcaaaggcg gcataactgg 15

80520

gtagggcagc agattcagga ggttatcatg ctgccgttca atattgcggc ttatacgata 80580

ctcctgtacg caacgaaata tatatttttc ttctttgcgt cagcccggta tctgtatctt 80640

atactcctgg agatcgtcac gccgatagcc gtaatactct acatggacga gaaaacgagg 80700 20

8068

-134-

cattatacgc acgcatacct gaaaaacctg tttgtctgtt acaggtcgtt cacgagatca 80760

gcatcaaccc cgattttatg aaccgggaag atcgggactg gcattctacc ctggtacatg

80820

aaatgtgcca tttgtggcag gaggatttcg gcaggccgag ccggggaggg tatcataatt 80880 5

cgcaatgggc tgacaagatg atccaggtcg gactgatgcc gtccgacacc ggggaggccg

80940

gaggcaaaag gacaggccag agcattacgc attatatcat tccgggaggg aagttcgaca

81000

acttcttcgt cttaattctc acactactca gccggaactt gacagaacga atctgatcgc 81060 10

tttgcaagct actctgaaag gtgatgcaat tgatcaagat gagaaaaatg ccgtcattac 81120

ttctccgtat gtagctgtat atgataatat tttggctgct gaagatgttc gtatcgctga 81180

taaggaaact ttgtttgaag gtggtaatgc tgctcattat gcaactacat tcgatgcttg 81240

tacgaaagaa gaacaacttg atctcgatct ggaaagtacg ggtagttgcg tcgatagtcg 81300 15

gatagatcag gctgatagtt cccttgaaca gttcgtcgcc atatacatcc agcttcacat 81360

ctaccggttc gcctttcttc accttcgtga agtaggtttc agacacattg atcatcagct 81420

tgaccggagt gatctgctct actaccagca ccggacttcc gccactatac atatcaccat 81480

tatcgtaatt aggggcagtg attactccca acttgatctc gatctggaaa gtacgggtag 81540

ttgcgtcgat agtcggatatag atcaggctga tagttccctt gaacagttcg tcgccatata 81600 20

8068

-135-

catccagctt cacatctacc ggttcgcctt tcttcccctt cgtgaagtag gtttcagaca 81660

cattgatcat cagcttgacc ggagtgatct gctctactac cagcaccgga cttccgccac 81720

tatacatatc accattatcg taattacggg cagtgattac tcccaactgg aacaggaagc

81780

cagggaaaac cggggagaagg ccgggaaact gcaaacggat ctcgaaatag cccggcagga 5

81840

gaaaggaact ccggccgtcg gatgcaatac gcacaagatc ctggagatcg aggagcgtat

81900

cgacgaggtg aagaagatac cgacattcaa cgatacggtt tatgagatag accgtaatac

81960 10

gctggatatg tgggtgaaaa ggttaaagga cgaactaaag agataagcct atgtttgcgc

82020

ccatgcggtc aaggtatttg aaagcatctt cggcgaaagc ttcgtgacgc gcatcgccgg

82080

ggaaattcag ttctacgttt ttgttagtca gatcgattgc tttggcagaa ctgtcaacgg 82140 15

aatgtaccag ctttgcacct ccacgcatag cgtagaagga gaaaccgccg gtgtagcaga

82200

acatattcag taccgaacgg tctttagaat aatgctccag cagtgaacgg ttttcgcgtt 82260

ggtctacgaa gaacacaagg tgcagcaacg tttgaactcg gatctttcga tcgccggggt

82320 20

8068

-136-

tctgataacc cagtacgacg gaagaaagaa cctgaacaag agcgtttcgg aactggtaca

82380

ggaaacattc cagggcaaag tgttcagcac ccatgtacgc aactccattg cgctggccga

82440

agccccgaca caagggcagg atatttttca ctatgccccc aaatctgccg gggcagagga 5

82500

ctacgagggt gtatgtaacg aactgctaca caaggtgcag caacgtttga actcggatct

82560

ttcgatcgcc ggggttctga taacccagta cgacggaaga aagaacctga acaagagcgt

82620 10

ttcggaactg gtacaggaaa cattccaggg caaagagttc agcacccatg tacgcaactc

82680