Skin care composition comprising a combination of peptides
Patent Information
- Application Number
- CN202280010735.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Priority Date
- 2021-01-22
- Filing Date
- 2022-01-21
- Publication Date
- 2026-09-08
- Estimated Expiration
- 2042-01-21
AI Technical Summary
然而,肽可能是昂贵的,尤其是已知提供护肤有益效果的那些
[0006] This article discloses a skincare composition comprising: a combination of palmitoyl dipeptide-7 (pal-KT) and acetyl tetrapeptide-11 (ac-PPYL) [SEQ ID NO:1]; and a dermatologically acceptable carrier; and also discloses a method for treating a skin condition comprising applying the novel composition of this article to a target skin portion for desired treatment. The combination of peptides can improve cellular ATP levels and/or upregulate certain genes involved in ECM repair and renewal processes, in some cases synergistically.
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Abstract
Description
Technical Field
[0001] This disclosure relates generally to skin care compositions and methods for improving cellular energy levels and renewing the extracellular matrix. More specifically, the invention relates to a combination of peptides that synergistically regulate certain genes involved in cellular energy production and extracellular matrix repair. Background Technology
[0002] Skin is the first line of defense against environmental damage, which can harm sensitive underlying tissues and organs, and it plays a crucial role in a person's physical appearance. Signs of skin aging, such as wrinkles and age spots, are an unwelcome reminder of the passing of youth. Therefore, in today's youth-conscious society, addressing signs of skin aging has become a rapidly growing industry.
[0003] Skin is composed of a variety of different cells that work together in a dynamic and complex relationship to maintain skin health. However, as skin cells age or become damaged, they may lose the functions needed to maintain youthful, healthy skin. Skin cells can be damaged by a variety of endogenous and exogenous stressors, such as ultraviolet radiation, pollution, and smoking. In some cases, these stressors can lead to the production of reactive oxygen species (ROS), which interfere with normal cellular processes. As a response, cells have evolved defenses against ROS, but these defenses can be overwhelmed by stressor-induced spikes in ROS, leading not only to acute but also chronic changes in intracellular homeostasis. As ROS accumulate over time, they cause oxidative stress at the cellular level, which can ultimately manifest as visible signs of aging, such as fine lines, wrinkles, hyperpigmentation, and thinning skin.
[0004] The uses of peptides in skincare compositions are generally known. The variety of commercially available peptides and the range of skincare benefits they offer make them attractive ingredients for use in skincare compositions. For example, US 9,597,274 describes the use of peptides derived from growth factors (such as growth differentiation factor 11) to improve skin health and / or appearance. Similarly, US 10,668,000 describes skincare compositions that may contain a variety of different peptides that are active in the synthesis of ECM proteins and generally improve skin appearance. However, peptides can be expensive, especially those known to provide skincare benefits. Therefore, peptides are typically added to skincare compositions in relatively low amounts, making it important to select peptides that provide good efficacy at low concentrations.
[0005] Therefore, it is desirable to provide a peptide-containing skincare composition that can improve the health and appearance of human skin, particularly skin exhibiting visible signs of aging. Specifically, it is desirable to provide a peptide-containing skincare composition that improves cellular energy production and / or ECM repair and renewal processes in skin cells by targeting specific genes involved in these biochemical pathway groups. It is also desirable to provide a combination of peptides that delivers the desired efficacy at low concentrations. Summary of the Invention
[0006] This article discloses a skincare composition comprising: a combination of palmitoyl dipeptide-7 (pal-KT) and acetyl tetrapeptide-11 (ac-PPYL) [SEQ ID NO:1]; and a dermatologically acceptable carrier; and also discloses a method for treating a skin condition comprising applying the novel composition of this article to a target skin portion for desired treatment. The combination of peptides can improve cellular ATP levels and / or upregulate certain genes involved in ECM repair and renewal processes, in some cases synergistically. Detailed Implementation
[0007] The use of peptides to improve skin health and appearance is generally known. However, it has now been surprisingly discovered that the combination of palmitoyl dipeptide-7 (“pal-KT”) and acetyl tetrapeptide-11 (ac-PPYL) [SEQ ID NO:1] promotes cellular energy production and ECM repair and renewal processes. Specifically, the combination of pal-KT and ac-PPYL [SEQ ID NO:1] synergistically regulates the expression of key genes known to be involved in cellular bioenergetics and ECM repair and renewal. Improving cellular energy production and / or ECM repair and renewal is important for improving the health and / or appearance of skin, especially skin exhibiting visible signs of aging.
[0008] References to "implementation" or similar methods herein refer to specific materials, features, structures, and / or characteristics described in connection with that implementation being included in at least one implementation, or optionally multiple implementations, but do not imply that all implementations include the described materials, features, structures, and / or characteristics. Furthermore, materials, features, structures, and / or characteristics may be combined in any suitable manner in different implementations, and materials, features, structures, and / or characteristics may be omitted or replaced in their description. Therefore, unless otherwise stated or declared as incompatible, although not expressly illustrated in the combination, the implementations and aspects described herein may include elements or components of other implementations and / or aspects, or may be combined with elements or components of other implementations and / or aspects.
[0009] In all embodiments, unless otherwise specified, all ingredient percentages are based on the weight of the cosmetic composition. Unless otherwise specified, all ratios are by weight. Significant figures do not express any limitation on the quantities shown or on the accuracy of the measurement. All values should be understood to be modified by the word “about” unless otherwise specified. Unless otherwise specified, all measurements are understood to have been performed at approximately 25°C and ambient conditions, where “ambient conditions” means conditions at approximately 1 atmosphere and approximately 50% relative humidity. All numerical ranges are inclusive and can be combined to form narrower ranges not explicitly disclosed. For example, the upper and lower limits of the depicted ranges are interchangeable to form additional ranges.
[0010] The compositions of the present invention may comprise, consist of, or be composed of the basic components described herein, as well as optional ingredients. As used herein, “consistently consisting of” means that a composition or component may contain only additional ingredients that do not substantially alter the essential and novel features of the composition or method protected by the claims. As used in the specification and appended claims, unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well.
[0011] sequence list
[0012] A sequence listing of the amino acid or nucleotide sequence of SEQ ID NO:1 and the nucleotide sequences of SEQ ID NO:2 and SEQ ID NO:3 (which are primary sequences and include variants with conserved modifications) is submitted with this application as an ASCII text file entitled “15965_seq_list_ST25”. This ASCII text file was created on January 19, 2021, and is 138 KB in size. Subject matter from this ASCII text file is incorporated herein by reference in accordance with MPEP §605.08 and 37 CFR §1.52(e).
[0013] definition
[0014] The word “about” modifies a specific value by referring to a range equal to or less than 20 percent (+ / - 20%) of the specified value (e.g., less than 15%, 10%, or even less than 5%).
[0015] As used with reference to the composition, “apply” means applying or spreading the composition of the invention onto the surface of human skin, such as the epidermis.
[0016] "Cosmetic composition" means a composition that contains cosmetic agents and is intended for non-therapeutic (i.e., non-medical) use. Examples of cosmetic compositions include tinted cosmetics (such as foundation, lipstick, concealer, and mascara), skin care compositions (such as moisturizers and sunscreens), personal care compositions (such as rinse-off and leave-on bath products and soaps), and hair care compositions (such as shampoos and conditioners).
[0017] In this article, “derivative” means an amide, ether, ester, amino, carboxyl, acetyl, and / or alcohol derivative of a given compound.
[0018] "Effective amount" means an amount of compound or composition sufficient to significantly induce a positive beneficial effect on keratinocytes during the treatment period. Positive beneficial effects can be health, appearance, and / or sensory benefits, including individual or combined beneficial effects disclosed herein. In a specific example, an effective amount of sucrose esters and fatty alcohols is an amount sufficient to increase cellular ATP levels that are reduced due to oxidative stress.
[0019] "Skincare" refers to conditioning and / or improving skin condition (e.g., skin health, appearance, or texture / feel). Some non-limiting examples of improving skin condition include improving skin appearance and / or feel by providing a smoother, more even appearance and / or feel; increasing the thickness of one or more layers of skin; improving skin elasticity or resilience; improving skin firmness; and reducing the oily, shiny, and / or dull appearance of skin; improving skin hydration or moisturization; improving the appearance of fine lines and / or wrinkles; improving skin peeling or flaking; plumping the skin; improving skin barrier properties; improving skin tone; reducing the appearance of redness or rashes; and / or improving skin radiance, luminosity, or translucency.
[0020] "Skincare active ingredients" refer to compounds or combinations of compounds that, when applied to the skin, provide immediate and / or long-lasting beneficial effects to the skin or the cell types typically present therein. Skincare active ingredients can modulate and / or improve the skin or its related cells (e.g., improve skin elasticity, hydration, skin barrier function, and / or improve cell metabolism).
[0021] "Skincare composition" means a composition that contains skincare active ingredients and regulates and / or improves skin condition.
[0022] "Synergy" and its variants refer to the cellular energy production and / or ECM repair effects provided by the combination of palmitoyl dipeptide-7 (pal-KT) and acetyl tetrapeptide-11 [SEQ ID NO:1] being greater than the expected additive effects of these components alone. For example, synergy is demonstrated when the combination of pal-KT and acetyl tetrapeptide-11 [SEQ ID NO:2] increases the upregulation of PPARA [SEQ ID NO:2] and / or MSMO1 [SEQ ID NO:3] beyond the calculated additive effects of these components individually.
[0023] As used herein, “treatment period” refers to the length of time and / or frequency of application of a material or composition to the target skin surface.
[0024] "Upregulation" and its variations refer to an increase in gene expression. Conversely, "downregulation" refers to a decrease in gene expression. Upregulation and downregulation relative to a specific gene can be determined using gene regulation assays described in more detail below.
[0025] Skin care composition
[0026] This novel skincare composition is intended for topical application to human skin to improve cellular energy production and / or ECM health. The skincare composition of this invention contains safe and effective amounts of palmitoyl dipeptide-7 (pal-KT) and acetyl tetrapeptide-11 (ac-PPYL) [SEQ ID NO:1]. The combination of these two effective amounts has been shown to upregulate PPARA [SEQ ID NO:2] and MSMO1 [SEQ ID NO:3], and therefore this combination is believed to be involved in cellular energy production. See, Lopez-Leon, S et al., “Sports genetics: the PPARA gene and athletes' high ability in endurancesports. A systematic review and meta-analysis,” Biology of sport, Vol. 33, 1 (2016): pp. 3–6. Effective amounts of pal-KT and ac-PPYL [SEQ ID NO:1] can also synergistically upregulate MSMO1 (SEQ ID NO:3), both of which are believed to be involved in cholesterol synthesis and in the repair and renewal of the skin barrier. See He M. et al., “The role of sterol-C4-methyl oxidase in epidermal biology”, Biochim BiophysActa. March 2014; 1841(3):331-5.
[0027] PPARA and MSMO1 have been shown to be downregulated due to dermal aging of the skin (i.e., time-related aging and / or photoaging of the dermis). However, in some cases, the combination of pal-KT and ac-PPYL [SEQ ID NO:1] synergistically upregulates these genes and can even exhibit a synergistic effect of 1.2 or greater (e.g., 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, or 1.9 or greater). The compositions described herein may contain a pal-KT to ac-PPYL [SEQ ID NO:1] weight ratio of 10:1 to 1:10 (e.g., 5:1 to 1:10, 5:1 to 1:5, 1:1 to 1:5, or 1:1 to 1:10).
[0028] The skincare compositions described herein may be cosmetic compositions, pharmaceutical compositions, or medicated cosmetic compositions, and may be provided in various product forms, including but not limited to solutions, suspensions, lotions, creams, gels, toners, sticks, sprays, aerosols, ointments, cleansing liquids and solid sticks, pastes, foams, mousses, shaving creams, wipes, strips, patches, motorized patches, hydrogels, film-forming products, facial and skin masks (with and without insoluble sheets), cosmetics such as foundation, eyeliner, and eyeshadow. In some cases, the composition form may conform to a selected, dermatologically acceptable carrier. For example, the composition (and carrier) may be provided as an emulsion (e.g., water-in-oil, oil-in-water, or oil-in-water) or an aqueous dispersion.
[0029] The compositions described herein can be prepared using conventional methods for preparing topical skincare compositions. Such methods typically involve mixing the ingredients to a relatively homogeneous state in one or more steps, with or without heating, cooling, applying vacuum, etc. Preferably, the compositions are prepared to optimize stability (physical stability, chemical stability, photostability) and / or delivery of the active substance. Such optimization may include an appropriate pH (e.g., less than 7), excluding substances that can complex with the active agent and thus negatively affect stability or delivery (e.g., excluding contaminating iron), using methods to prevent complex formation (e.g., appropriate dispersants or double-compartment packaging), using appropriate photostability methods (e.g., combining with sunscreens, using opaque packaging), etc.
[0030] Vitamin B3 compounds
[0031] The compositions described herein may optionally contain a safe and effective amount of a vitamin B3 compound. In some cases, the compositions of the present invention may contain 0.01% to 10% (e.g., 0.1% to 10%, 0.5% to 5%, or even 1% to %) of a vitamin B3 compound based on the weight or volume of the composition.
[0032] As used in this article, "vitamin B3 compound" refers to a compound having the following formula:
[0033]
[0034] Wherein: R is CONH2 (i.e., nicotinamide), COOH (i.e., nicotinic acid) or CH2OH (i.e., nicotinic alcohol); their derivatives; and a salt of any of the aforementioned substances.
[0035] Exemplary derivatives of vitamin B3 compounds include nicotinic acid esters, which include non-vasodilatory nicotinic acid esters (e.g., nicotinic acid tocopheryl ester, nicotinic acid tetradecyl ester), nicotinamide nucleoside, nicotinic amino acid, nicotinic acid esters of carboxylic acids, nicotinic acid N-oxide, and nicotinamide N-oxide.
[0036] Dipeptide
[0037] The compositions described herein contain a safe and effective amount of palmitoylated dipeptide, pal-KT (INCI: palmitoyl dipeptide-7). In some cases, pal-KT may be present in the compositions of the present invention at 0.0001% to 3% (e.g., 0.001% to 2%, 0.01% to 1%, or 0.1% to 0.5%). Pal-KT is marketed under the trade name... Derived from Sederma (France).
[0038] Tetrapeptide
[0039] The compositions described herein contain a safe and effective amount of acetylated tetrapeptide ac-PPYL [SEQ ID NO:2] (INCI: Acetyl Tetrapeptide-11). In some cases, ac-PPYL may be present in the compositions of the present invention at 0.0001% to 3% (e.g., 0.001% to 2%, 0.01% to 1%, or 0.1% to 0.5%). Ac-PPYL is available under the trade name SYNIORAGE from BASFCare Creations (New Jersey).
[0040] Dermatologically acceptable carriers
[0041] The compositions described herein include dermatologically acceptable carriers (which may be referred to as "carriers"). The phrase "dermatologically acceptable carrier" means that the carrier is suitable for topical application to keratinocytes, has good aesthetic properties, is compatible with the active substances in the composition, and does not cause any unreasonable safety or toxicity problems. In one embodiment, the carrier is present in an amount of about 50% to about 99%, about 60% to about 98%, about 70% to about 98%, or about 80% to about 95% by weight of the composition.
[0042] The carrier can take many forms. In some cases, the solubility or dispersibility of the components (e.g., extracts, sunscreen active ingredients, additives) determines the form and characteristics of the carrier. Non-limiting examples include simple solutions (e.g., aqueous or anhydrous), dispersions, emulsions, and solid forms (e.g., gels, sticks, flowable solids, or amorphous materials). In some cases, dermatologically acceptable carriers are in the form of emulsions having a continuous aqueous phase (e.g., oil-in-water or water-in-oil-in-water emulsions) or a continuous oil phase (e.g., water-in-oil or water-in-oil-in-oil emulsions). The oil phase of the emulsion may contain silicone oils, non-silicone oils (such as hydrocarbon oils, esters, ethers), and mixtures thereof. The aqueous phase may contain water and water-soluble ingredients (e.g., water-soluble moisturizers, conditioning agents, antimicrobial agents, humectants, and / or other skin-care active ingredients). In some cases, the aqueous phase may contain components that are not water, including but not limited to water-soluble moisturizers, conditioning agents, antimicrobial agents, humectants, and / or other water-soluble skin-care active ingredients. In some cases, the non-aqueous components of the composition include wetting agents, such as glycerin and / or other polyols.
[0043] In some cases, the compositions herein are in the form of an oil-in-water (“O / W”) emulsion that provides a mild and non-greasy sensory experience. Suitable O / W emulsions herein may comprise a continuous aqueous phase of greater than 50% by weight of the composition, with the remainder being a dispersed oil phase. The aqueous phase may comprise 1% to 99% water by weight, along with any water-soluble and / or water-miscible components. In these cases, the dispersed oil phase will typically be present at less than 30% by weight of the composition (e.g., 1% to 20%, 2% to 15%, 3% to 12%, 4% to 10%, or even 5% to 8%) to help avoid some undesirable sensory effects of oily compositions. The oil phase may comprise one or more volatile and / or non-volatile oils (e.g., vegetable oils, silicone oils, and / or hydrocarbon oils). Some non-limiting examples of oils suitable for use in the compositions of the present invention are disclosed in U.S. Patent 9,446,265 and U.S. Publication 2015 / 0196464.
[0044] The carrier may contain one or more dermatologically acceptable diluents. As used herein, “diluent” means a material in which the skincare active ingredient described herein can be dispersed, dissolved, or otherwise incorporated. Some non-limiting examples of hydrophilic diluents include water, organic hydrophilic diluents such as lower monovalent alcohols (e.g., C1-C4) and low molecular weight diols and polyols, including propylene glycol, polyethylene glycol (e.g., molecular weight 200 g / mol to 600 g / mol), polypropylene glycol (e.g., molecular weight 425 g / mol to 2025 g / mol), glycerin, butylene glycol, 1,2,4-butanetriol, sorbitan ester, 1,2,6-hexanetriol, ethanol, isopropanol, sorbitan ester, butylene glycol, ether propanol, ethoxylated ether, propoxylated ether, and combinations thereof.
[0045] Conditioner
[0046] The compositions described herein may contain 0.1% to 50% by weight of a conditioning agent (e.g., 0.5% to 30%, 1% to 20%, or even 2% to 15%). Adding a conditioning agent can help provide the composition with desired sensory properties (e.g., a silky, lubricating feel upon application). Some non-limiting examples of conditioning agents include hydrocarbon oils and waxes, siloxanes, fatty acid derivatives, cholesterol, cholesterol derivatives, diglycerides, triglycerides, vegetable oils, vegetable oil derivatives, acetylglucosides, alkyl esters, alkenyl esters, lanolin, wax esters, beeswax derivatives, sterols and phospholipids, their salts, isomers and derivatives, and combinations thereof. Particularly suitable examples of conditioning agents include volatile or non-volatile silicone fluids, such as polydimethylsiloxane copolyols, dimethylpolysiloxanes, diethylpolysiloxanes, mixed C1-30 alkylpolysiloxanes, phenyl polydimethylsiloxanes, polydimethylsiloxane alcohols, polydimethylsiloxanes, polydimethylsiloxanes, silicone crosspolymers, and combinations thereof. Polydimethylsiloxanes may be particularly suitable because some consumers associate the sensory properties provided by certain polydimethylsiloxane fluids with good moisturizing properties. Other examples of silicone fluids suitable as conditioning agents are described in U.S. Patent 5,011,681.
[0047] rheology modifiers
[0048] The compositions described herein may contain 0.1% to 5% of a rheology modifier (e.g., a thickener) to provide suitable rheological and skin-feel properties to the composition. Some non-limiting examples of thickeners include cross-linked polyacrylate polymers, polyacrylamide polymers, polysaccharides, gums, and mixtures thereof. In a particularly suitable example, the composition may contain a superabsorbent polymer thickener, such as sodium polyacrylate, starch-grafted sodium polyacrylate, or combinations thereof. Some non-limiting examples of superabsorbent polymer thickeners are described, for example, in U.S. Patent 9,795,552.
[0049] Some consumers have found that compositions using siloxane fluids as conditioners have an undesirable greasy or heavy feel. Therefore, it may be desirable to provide compositions that are free of or substantially free of siloxane fluids. It may also be desirable to customize superabsorbent polymer thickeners to provide a light, breathable feel to the composition, for example, by adjusting the amount of water in the composition, the water:oil ratio (e.g., 12:1 to 1:1), and / or the ratio of water to thickener or oil to thickener.
[0050] emulsifier
[0051] When a dermatologically acceptable carrier is in emulsion form, it may be desirable to include an emulsifier to provide a stable composition (e.g., no phase separation). When an emulsifier is included, it may be present in amounts from 0.1% to 10% (e.g., 1% to 5%, or 2% to 4%). The emulsifier may be nonionic, anionic, or cationic. Some non-limiting examples of emulsifiers suitable for use herein are disclosed in U.S. Patent Nos. 3,755,560; 4,421,769 and McCutcheon's "Detergents and Emulsifiers," North American Edition, pp. 317-324 (1986).
[0052] Other optional ingredients
[0053] The compositions of the present invention may optionally contain one or more additives commonly used in cosmetic compositions (e.g., colorants, skin-care active substances, anti-inflammatory agents, sunscreens, emulsifiers, buffers, rheology modifiers, combinations thereof, etc.), provided that the additive does not adversely alter the beneficial effects on skin health or appearance provided by the compositions of the present invention. When incorporated into a composition, the additive should be suitable for contact with human skin tissue without undue toxicity, incompatibility, instability, allergic response, etc. Some non-limiting examples of added active substances include vitamins, minerals, peptides and peptide derivatives, glycosamines, sunscreens, oil-controlling agents, particles, flavonoids, hair growth regulators, antioxidants and / or antioxidant precursors, preservatives, protease inhibitors, tyrosinase inhibitors, anti-inflammatory agents, moisturizers, exfoliating agents, skin brighteners, sun-free tanning agents, lubricants, anti-acne active substances, anti-cellulite active substances, chelating agents, anti-wrinkle active substances, anti-atrophy active substances, phytosterols and / or plant hormones, N-acyl amino acid compounds, antimicrobial agents, and antifungal agents. Other non-limiting examples of adjunct ingredients and / or skincare active substances applicable herein are described in U.S. Patent Publications 2002 / 0022040, 2003 / 0049212, 2004 / 0175347, 2006 / 0275237, 2007 / 0196344, 2008 / 0181956, 2008 / 0206373, 2010 / 00092408, 2008 / 0206373, 2010 / 0239510, and 2010 / 0189669. US Patent Nos. 2010 / 0272667, 2011 / 0262025, 2011 / 0097286, 2012 / 0197016, 2012 / 0128683, 2012 / 0148515, 2012 / 0156146 and 2013 / 0022557, and US Patent Nos. 5,939,082, 5,872,112, 6,492,326, 6,696,049, 6,524,598, 5,972,359 and 6,174,533.
[0054] When optional ingredients are included in the compositions herein, it may be desirable to select ingredients that do not form complexes or otherwise undesirably interact with other ingredients in the composition, particularly pH-sensitive ingredients such as nicotinamide, salicylates, and peptides. When present, optional ingredients may be included in amounts from 0.0001% to 50%; 0.001% to 20%; or even 0.01% to 10% (e.g., 50%, 40%, 30%, 20%, 10%, 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.1%) based on the weight of the composition.
[0055] How to use
[0056] The method of the present invention includes identifying a target skin portion to be treated and applying a composition comprising an effective amount of a vitamin B3 compound, pal-KT, ac-PPYL [SEQ ID NO:1], and optionally one or more additional skin-care active substances to the target skin portion. The target skin portion may be on the surface of facial skin (such as the forehead, perioral region, chin, periorbital region, nose, and / or cheeks) or another part of the body (e.g., hands, arms, legs, back, chest). The person to be treated or the target skin portion may be a person or a target skin portion exhibiting signs of skin aging (e.g., fine lines, wrinkles, hyperpigmentation). In some cases, the target skin portion may not exhibit signs of skin aging, but if the skin portion is known to exhibit visible signs of aging (e.g., sun-exposed skin), the user may still wish to treat that skin portion. In this way, the method and composition of the present invention can be used preventively to help delay visible signs of skin aging.
[0057] The composition may be applied to the target skin area and, if necessary, to the surrounding skin at least once daily, twice daily, or more frequently daily during the treatment period. When applied twice daily, the first and second applications should be at least 1 to 12 hours apart. Typically, the composition may be applied in the morning and / or at bedtime. The treatment period described herein is ideally the time sufficient to improve the appearance of the skin for pal-KT and ac-PPYL [SEQ ID NO:1]. The treatment period may last at least 1 week (e.g., about 2 weeks, 4 weeks, 8 weeks, or even 12 weeks). In some cases, the treatment period may be extended to several months (i.e., 3 months to 12 months). In some cases, the composition may be applied for most of the week (e.g., at least 4, 5, or 6 days a week), at least once daily or even twice daily during a treatment period of at least 2, 4, 8, or 12 weeks.
[0058] The application of the composition can be achieved through topical application. Regarding the application of the composition, the terms "topical," "local," and "partially" refer to delivering the composition to a target area (e.g., a wrinkle or portion thereof) while minimizing delivery to skin surfaces that are not intended to be treated. The composition may be applied to and gently massaged into the skin area. The form of the composition or a dermatologically acceptable carrier should be chosen to facilitate topical application. While some embodiments herein envision topical application of the composition to a specific area, it should be understood that the compositions herein can be applied more comprehensively or extensively to one or more skin surfaces. In some embodiments, the compositions herein can be used as part of a multi-step cosmetic regimen, wherein the compositions of the present invention may be applied before and / or after one or more other compositions.
[0059] Gene regulation assay
[0060] This method provides a way to measure the ability of a compound or material to regulate the expression of target genes such as PPARA [SEQ ID NO:2] or MSMO1 [SEQ ID NO:3].
[0061] cell tertiary keratinocytes (tKC)
[0062] BJ fibroblasts
[0063] planking Cells were plated the day before processing.
[0064] For tertiary keratinocytes: For 12-well plates (e.g., type I collagen-coated plates, Corning catalog number 356500), 100,000 cells / well in 2 ml of culture medium / well; or for 24-well plates, 50,000 cells / well in 1 ml of culture medium / well.
[0065] For BJ fibroblasts: 88,000 cells / well in 2 ml of medium / well for 12-well plates (e.g., Corning catalog number 3512); or 44,000 cells / well in 1 ml of medium / well for 24-well plates.
[0066] culture medium For tertiary keratinocytes: EpiLife (e.g., Thermo Fisher Scientific catalog number MEPI500CA+HKGS (e.g., Thermo Fisher Scientific catalog number S-001-5).
[0067] For BJ fibroblasts: EMEM (e.g., ATCC catalog number 30-2003) + 10% FBS (e.g., HyClone catalog number SH30071.02).
[0068] The cells were treated in the culture medium and aliquoted into dosing plates. When cells needed to be treated, all plates were removed from the incubator simultaneously. One plate was used at a time; the culture medium was removed and the treatment was added as follows:
[0069] -- Decant the culture medium from the cell plate.
[0070] Simply blot the inverted board dry on a paper towel.
[0071] --Place the lid back onto the board and move the board into the biosafety cabinet.
[0072] --Use a multichannel pipette to transfer the treatment from the dosing plate to the cell plate, one column at a time.
[0073] Once all plates have been processed, transfer them to an incubator at 37°C, 5% CO2, and 90% humidity. Approximately 15 to 30 minutes before the end of the treatment period, observe cells from a representative well of each treatment via a microscope, then return the plates to the incubator. When the treatment time is complete, remove all plates from the incubator. Decant the culture medium from each plate and blot the plates dry on paper towels. Add 350 μl of Qiagen Buffer RLT to each well to lyse the cells, and transfer the lysates to 2 ml Eppendorf tubes and store at -20°C until ready for genomics.
[0074] Wafergen method: Total RNA purification and qPCR
[0075] Cell lysates were thawed at 4°C and then isolated using the Biomek FxP and RNAdvance Tissue Isolation Kit (Beckman Coulter, part number A32646). RNA was quantified using a Nanodrop 8000 (Nanodrop, ND-8000). cDNA was generated using 500 ng of total RNA and the Applied Biosystems High Capacity cDNA and Reverse Transcription Assay Kit (Applied Biosystems, part number 4368814). cDNA, assay samples, and dilution buffer from the PrimeTime GeneExpression MasterMix (IDT, part number 1055771) were plated onto a Wafergen MyDesign SmartChip (TakaraBio, part number 640036) using a Wafergen Nanodispenser. Slides were then loaded into a SmartChip circulator and qPCR was performed under the following PCR conditions:
[0076] Hold phase: 50°C for 2 minutes (heating), then 95°C for 10 minutes.
[0077] PCR phase (40 cycles): 95°C for 15 seconds, then 60°C for 1 minute.
[0078] Export the data in .txt file format for analysis.
[0079] ATP assay for hydrogen peroxide stress
[0080] Skin cells (such as keratinocytes and fibroblasts) combat reactive oxygen species by using energy to produce enzymes and reducing equivalents (such as GSH), which leads to depletion of cellular ATP levels. Lower energy levels make cells more susceptible to reduced ability to adapt and function normally. Therefore, increasing cellular ATP levels helps cells combat stress and maintain sufficient energy for normal homeostasis.
[0081] Hydrogen peroxide is a well-known alternative to ROS. When skin cells are treated with high levels (e.g., 200 μM to 500 μM) of hydrogen peroxide, a decrease in cellular ATP levels of approximately 10% is observed in unstressed cells within one hour. Cellular ATP levels can be quantified using a CELL TITER GLO assay kit from Promega or an equivalent, where the luminescent signal is proportional to the amount of ATP present.
[0082] Method Overview :
[0083] This assay was performed using expanded tKC from a stockpile. Cells were expanded in culture flasks for 5 days, triedpsinized, seeded, and then grown in 96-well plates. After 1 day of growth in 96-well plates, the cells in column 1 were left untreated and unstressed. The cells in columns 2 through 12 were treated with hydrogen peroxide (300 μM in medium). Column 2 was left untreated, while columns 3 through 12 were treated with serial dilutions of the test material for 1 hour (37°C, 5% CO2 incubator).
[0084] Cell preparation :
[0085] 1. Seed cells at a rate of 10,000 cells / well, 100 μL total volume / well in a suitable 96-well plate (e.g., CORNING white transparent substrate #3903 or equivalent).
[0086] 2. Incubate cells at 37°C, 5% CO2, and 95% humidity for 24 hours until the treatment day. For example, cells can be seeded on Monday and measured on Tuesday.
[0087] deal with :
[0088] 1. Aspirate the culture medium from the cell plate.
[0089] 2. Add 100 μL of culture medium to wells A1 to H1 of column 1.
[0090] 3. Add 100 μL of culture medium containing 300 μM hydrogen peroxide to all wells of columns 2 through 12.
[0091] 4. Add the carrier control to column 2 (A2 to H2), and add 1 μL of the treatment dilution to columns 3 through 11.
[0092] 5. Add 1 μl of 40.9 mM nicotinamide to all wells of column 12 to bring the final nicotinamide level to 409 μM (positive control).
[0093] 6. Place in a 37℃, 5% CO2 incubator for 1 hour.
[0094] 7. Remove the culture medium from all wells.
[0095] 8. Add 100 μL of CELL TITER GLO reagent to each well according to the manufacturer's instructions.
[0096] 9. Incubate at room temperature for 5 to 10 minutes.
[0097] 10. Read the light emission value on a suitable plate reader.
[0098] Luminescence detection :
[0099] Use a BioTek SYNERGY NEO brand card reader or equivalent.
[0100] Example
[0101] Example 1: Formulation .
[0102] Table 1 below provides examples of the skincare compositions of the present invention. An exemplary composition was prepared by blending phase A components with a suitable mixer (e.g., a Tekmar RW20DZM or equivalent) and heating to a temperature of 70°C to 80°C, while maintaining the temperature through stirring. Separately, phase B components were blended with a suitable mixer and heated to 70°C to 75°C, while maintaining the temperature during blending. Phase B was added to phase A while thoroughly mixing to form an oil-in-water (O / W) emulsion. The emulsion was then milled for 5 minutes using a suitable grinder (e.g., a Tekmar T-25 or equivalent). When the emulsion reached 60°C, phase C was added while continuing to mix. When the emulsion reached 40°C, the components of phases D and E were added to the emulsion. The emulsion was then milled for 5 minutes to provide a homogeneous composition.
[0103] Table 1
[0104]
[0105]
[0106] Example 2: pal-KT and Ac-PPYL [SEQ ID NO:1] synergistically upregulate PPARA [SEQ ID NO:2] and MSMO1 [SEQ ID NO:3].
[0107] This example demonstrates that the combination of pal-KT and ac-PPYL [SEQ ID NO:1] synergistically upregulates PPARA [SEQ ID NO:2]. The test and control compositions were prepared as described above in the gene regulation assay and tested accordingly. The pal-KT used in this example was PALESTRINA pal-KT from Sederma (France), and the ac-PPYL was SYNIORAGE tetrapeptide from BASF Care Creations (New Jersey). The results of this assay are summarized in Table 2 below. P+A refers to the combination of pal-KT (P) and ac-PPYL (A) [SEQ ID NO:1].
[0108] The synergy factor is calculated as follows:
[0109]
[0110] Synergy factors with p-values ≤ 0.05 and greater than 1.00 indicate statistically significant synergistic effects. A preferred synergy factor is 1.3 or greater.
[0111] Table 2
[0112]
[0113]
[0114] As shown in Table 2, not all combinations of pal-KT and ac-PPYL [SEQ ID No:1] produced the expected synergistic effect. Test sample combinations containing 1 ppm pal-KT (pal-KT to tetrapeptide ratios of 1:13.5 to 100:1.35) did not exhibit a synergistic factor of 1.3 or greater for upregulating MSMO1 [SEQ ID NO:3]. Test sample combinations containing 7.5 ppm pal-KT showed only the expected synergistic effect of upregulating PPARA [SEQ ID NO:2] at a ratio of approximately 1:2, although other combinations showed a lower synergistic ability to upregulate PPARA [SEQ ID NO:2]. Only one of the test samples containing 1 ppm was able to synergistically upregulate PPARA [SEQ ID NO:2], and none of the test samples showed a synergistic factor of 1.3 or greater. Therefore, the data suggest that peptide concentration and peptide ratio may both be important for upregulating PPARA [SEQ ID NO:2] and MSMO1 [SEQ ID NO:3].
[0115] Example 3: pal-KT and ac-PPYL [SEQ ID NO:3] improve cellular bioenergetics .
[0116] This embodiment demonstrates that pal-KT and ac-PPYL [SEQ ID NO:3] can counteract ROS-induced ATP depletion. Test cells exposed to hydrogen peroxide (a well-known reactive oxygen species) typically exhibit reduced ATP levels. Assay reagents capable of restoring ATP levels depleted due to ROS exposure are desirable. Assay reagents that synergistically restore ATP levels and exhibit a synergistic factor of 1.3 or greater are preferred. The peptides were tested according to the ATP assay for hydrogen peroxide stress described above. The results of this assay are summarized in Table 3 below. A synergistic factor greater than 1.00 with a p-value ≤ 0.05 indicates a statistically significant synergistic effect. A preferred synergistic factor is 1.3 or greater.
[0117] Table 3: ROS-induced ATP recovery
[0118]
[0119] As shown in Table 3, not all combinations of pal-KT and ac-PPYL [SEQ ID NO:1] synergistically restore intracellular ROS-depleted ATP levels. In fact, only combinations of pal-KT and ac-PPYL with a ratio of approximately 10:1 to 1:10 synergistically increase ATP production. In this embodiment, the test sample with a pal-KT to ac-PPYL [SEQ ID NO:1] ratio of approximately 1:1 appears to exhibit the highest synergistic effect.
[0120] Example 4: Dipeptide Specificity .
[0121] This example demonstrates the importance of selecting specific dipeptides to provide the desired synergistic upregulation of PPARA [SEQ ID NO:2] and / or MSMO1 [SEQ ID NO:3]. In this assay, amino acid rearrangements from pal-KT were performed to form a new dipeptide pal-TK. The test and control compositions were prepared as described above in the gene regulation assay and were tested accordingly. The results of this assay are summarized in Table 4 below. The fold change factor was calculated as follows.
[0122]
[0123] A factor of variation greater than 1 is required, preferably 1.3 or greater.
[0124] Surprisingly, pal-KT was able to upregulate PPARA [SEQ ID NO:2] and MSMO1 [SEQ ID NO:3] significantly better than pal-TK, and showed a factor of change greater than 1.3 for upregulating PPARA [SEQ ID NO:2] and MSMO1 [SEQ ID NO:3].
[0125] Table 4 - Specificity of pal-KT to pal-TK
[0126]
[0127] Surprisingly, as can be seen in Table 4, dipeptides with the same amino acids as pal-KT but in a different order do not provide the expected synergistic effect. These data suggest that specific peptide sequences are important for providing the desired synergistic effect.
[0128] Exemplary combinations
[0129] A. A skincare composition comprising:
[0130] a) A combination of palmitoyl dipeptide-7 (pal-KT) and acetyl tetrapeptide-11 (ac-PPYL) [SEQ ID NO:1], wherein the combination of pal-KT and ac-PPYL [SEQ ID NO:1] upregulates at least one of PPARA (SEQ ID NO:2) and MSMO1 (SEQ ID NO:3); and
[0131] b) Dermatologically acceptable carriers.
[0132] B. The composition according to paragraph A, wherein the combination of pal-KT and ac-PPYL [SEQ ID NO:1] synergistically upregulates at least one of PPARA (SEQ ID NO:2) and MSMO1 (SEQ ID NO:3).
[0133] C. The composition according to paragraph A or B, wherein the combination of pal-KT and ac-PPYL [SEQ ID NO:1] exhibits a synergistic factor of at least 1.3.
[0134] D. The composition according to any of the preceding paragraphs, wherein the pal-KT is present in an amount of 0.00005% to 5%.
[0135] E. The composition according to any of the preceding paragraphs, wherein the ac-PPYL [SEQ ID NO:1] is present in 0.00005% to 5%.
[0136] F. The composition according to any of the preceding paragraphs, wherein the pal-KT and ac-PPYL [SEQ ID NO:1] are present in a ratio of 10:1 to 1:10.
[0137] G. The composition according to any of the preceding paragraphs further comprises at least one additional ingredient selected from vitamins, minerals, peptides, glycosamines, sunscreens, oil-controlling agents, flavonoids, antioxidants, protease inhibitors, tyrosinase inhibitors, anti-inflammatory agents, moisturizers, exfoliating agents, skin brightening agents, anti-acne agents, anti-wrinkle agents, phytosterols, N-acyl amino acid compounds, antimicrobial agents, antifungal agents, pH adjusters, thickeners, preservatives, and combinations thereof.
[0138] H. The composition according to paragraph G, wherein the additional ingredient includes a vitamin B3 compound, a vitamin A compound, a vitamin E compound, sugars, or plant extracts.
[0139] I. A method for treating skin with cosmetics, comprising:
[0140] a) Identify the target skin region to be treated; and
[0141] b) During the treatment period, the skin care composition according to any of the preceding paragraphs is applied to the target skin portion, the skin care composition comprising a combination of palmitoyl dipeptide-7 (pal-KT) and acetyl tetrapeptide-11 (ac-PPYL) [SEQ ID NO:1] and a dermatologically acceptable carrier.
[0142] J. The method according to paragraph I, wherein the combination of pal-KT and ac-PPYL [SEQ ID NO:1] upregulates at least one of PPARA [SEQ ID NO:2] and MSMO1 [SEQ ID NO:3], preferably the combination of pal-KT and ac-PPYL [SEQ ID NO:1] synergistically upregulates at least one of PPARA [SEQ ID NO:2] and MSMO1 [SEQ ID NO:3].
[0143] K. The method according to paragraph I, wherein the combination of pal-KT and ac-PPYL [SEQ ID NO:1] improves cellular ATP levels, preferably synergistically, based on ATP assays for hydrogen peroxide stress.
[0144] L. The method described in paragraph I, wherein the processor is for at least 2 weeks.
[0145] M. According to the method described in the paragraph, which improves visible signs of skin aging.
[0146] N. A method for synergistically upregulating at least one of PPARA [SEQ ID NO:2] and MSMO1 [SEQ ID NO:3] in skin cells, comprising: contacting the skin with an effective amount of a combination of pal-KT and ac-PPYL [SEQ ID NO:1], wherein the effective amount of pal-KT and ac-PPYL [SEQ ID NO:1] upregulates at least one of PPARA [SEQ ID NO:2] and MSMO1 [SEQ ID NO:3].
[0147] The dimensions and values disclosed herein should not be construed as strictly limited to the precise numerical values cited. Rather, unless otherwise specified, each such dimension is intended to represent the stated value and a range around which it is functionally equivalent. For example, a dimension disclosed as “40 mm” is intended to represent “approximately 40 mm”.
[0148] Unless expressly excluded or otherwise limited, every reference cited herein, including any cross-references or related patents or patent applications, and any patent application or patent claiming priority to or benefiting from it, is incorporated herein by reference in its entirety. Reference to any reference is not an endorsement of it as prior art to any disclosed or protected art herein, nor is it an endorsement of any such invention, either on its own or in combination with any one or more references. Furthermore, where any meaning or definition of a term in this invention conflicts with any meaning or definition of the same term in referenced documents, the meaning or definition given to that term in this invention shall prevail.
[0149] While specific embodiments of the invention have been shown and described, it will be apparent to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. Therefore, it is intended that all such changes and modifications falling within the scope of the invention be covered by the appended claims. sequence list <110> Procter & Gamble <120> Skin care compositions and their application methods <130> 15965 <160> 3 <170> PatentIn version 3.5 <210> 1 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Description of the artificial sequence: Acetyl tetrapeptide-11 (ac-PPYL) <400> 1 Pro Pro Tyr Leu 1 <210> 2 <211> 93231 <212> DNA <213> Homo sapiens <400> 2 gtggacgcgg cggccccgcg gcgggggcag cgggcggcgg gggcggaggc ggccgctagc 60 gccctgcccg gcgccgcctc cttcggcgtt cgccccacgg accggcaggc ggcggaccgc 120 ggcccaggtg cccgggggcg ggcgggcggg cgggcgggaa cgcgcgcggg ggtccgcggt 180 ccgggcttcc caggtcccgg gacccggagg gcggcggacg ggggaggggc aggggctggg 240 cggcgcatgc gcggggcccg gggtctcggg gtctccgggt cccggggacc cgggggcccg 300 gggtgcgcgg ctggggacct gagggcgagg agcgaggaca cacaccgagg actcttgcga 360 gggatctcgg ggcccagctc ggcctccctc ctagcgctgg gggcctgccc ggaacccgag 420 tccgcggctg tccctggggt ttggcgctgc gcggaggtcg ggtctgggga ccgcagcgac 480 tctgggtctt cgggttgtcc cctcggaggg agggcccacg ggcggggaca tcgggacttg 540 ccctttcctc ggcgcagcgg agctggggcg tcgccgactc agaaggtgct ttccgagacc 600 tccagggatc tccgaggcga ggaaacccgg gccccggaca gaccgaccct gggtgggtgc 660 gcccggcttc tgccgtcgga cggagacgcg cgtgtttgtt cctccagctg cgaccacctt 720 tgaggaacgg ttcccacttt gtgccccaac gcggcggggc gaccccggac aggctgcgct 780 gggccgggtg gcttctctgc ggaagccgcg ccacgtcgct cccggtcggg gccgctgagg 840 gtcgggcgcc caggtctttc cggagtcccg ggctgcgcgg cccgcgtggt gcgggtgaag 900 ctggaggggc gcggggtggt gccagtggaa gtcaggaggg tcggccctgc cccctcacgc 960 accccaaccg ggcacaactg cacgcctgtg cttttctgaa gtctttttta aaagttaaaa 1020 gagaggaagt gtgctccaag tgtcaggatt ctttccaaga aaaacccaca gttgtccaat 1080 ggcctgggct tcgtgggacc tccggggctg cacgcccacg tcagcctcag ccgacccctg 1140 ccaggaaacc agggaggccc ctcctctccc agcctccttg ggataagggt gccttgggga 1200 actgggtcag ggcaaggaca cgggattttc ctgggaagga ccctgcgaca cccgtgtcgt 1260 tgcggggcag ggtcagcatg actttcctct tccaaggtga agagttgggg ggcatccaga 1320 gaacaaccgt aatcacttcc tccttcacct tcttactgcc aggctgaagc tcagggccct 1380 gtctgctctg tggactcaac agtttgtggc aagacaagct cagaactgag aagctgtcac 1440 cacaggtaaa tagaaggttt aattatactgt ttccagatgg aaatatttaa gtgttttcag 1500 tgtttacttc tgttgcacta cagaccagca atctggggt tattactttg tgatgcaagg 1560 ttagatacgt tttcagactg aaagtaaaat acatgtgcat ggattcattt ttttttttt 1620 tttttttttt tgagacggag tctcgctctg ccgcccaggc tggagtgcag tggcctaatc 1680 tcagatcaca gcaacctctg ccactggggt tcaagcgatt ctcttgcctc agcctcccga 1740 gtagctggga ttacaggcgc ctgccaccat gcccagctaa tttttgtagt tttagtagag 1800 gcggggtttc accatcttgg ccaggctgat cttgaactcc tgacctcatg atccacctgt 1860 tcctcccaaa gtgctgggat tacagacgtg agccaccgtg cctggcctag gattcacttt 1920 gaagttctga gttatgtgt gacttttgct aggaacttca ttgcttcgtg gcaggcatgt 1980 tttgtataat ttaaaacttg atgacattaa ctttgagaaa cgtgagtgct tactagaccc 2040 ttgggatgtc cacactgact ggtaccgagt agtgtactgt ctctgagctg ttttcatttt 2100 gatttgaata ttaagcagat ggcttcttga gatagacccg tgccagaaca tgccagggat 2160 aggctgaaga aacgggccag atgatacaaa tttgtgtggt caccatccat gagagaccag 2220 ggacactggg gctgatgatg acctctgcaa ctctgaagca aaagtaaact aattggcaag 2280 ttgggtgcgg tggctcactc ctgtaatccc agcactttgg aagctggggt gggcagatcg 2340 cttgaggcca ggagttcgag accagcctgg ccaacatggt gaaaccttgt ctctacaaaa 2400 aatagaaat attgcctggg catggtggcg gacatctgta atcccagcta ctcaagaaac 2460 tgaggcagga gaatcgcttg agcctgggag gtgaaggttt tagtgaactg agattgtgcc 2520 actgcactgc agcctgggcg ccagggcgag actccgtctc aaaaataaat aaataaaata 2580 aaattaatta actaattgac attagaaaaa aatgtttttt cttctttttc ccacatcctt 2640 tttttttt tttttttt tgtgacagag ttttgctctt gtcacccagg ctggagtgca 2700 gtggcatgat cttggctcac cgcaacgtcc acctcacgga ttcgaacaat actcctgcct 2760 cagcctcccg agtagctggg attacaggca ctcaccacca cacccggcta atttttgtat 2820 ttttagtaga ggtgggtttc accatgttgg ctgggctggt ctcaaactcc tgacctcagg 2880 tgaaccgcct gccttggcct cccaaagggc tgaggttaca ggtgcgagcc accgcgccgg 2940 gccctttcc gacatcttaa acgtaaagta ggagacgtgt cataatcatc gaatactgca 3000 gtggttttca ttagctcctg tttgtcaaac tttgaacag agttttaaaa attgtgtatc 3060 agccgggtgc ggtggctcac acctgtaatc tttgggaggc tgaggtgggc agatgacaag 3120 atcaggagtt tgagaccagc ctggccaata tggtgaaacc ctgtctctac taaaaataca 3180 aaaattagct gggcatggtg gcgggtgcct atggtcccag ctactcagga ggctgaagca 3240 ggagaatctc ttgaacccgg gaggtggagg ttgcagtgag ctgagatggc accacagcac 3300 cccagcctgg gtgacagagc aagactccgt ttccaaaaaa aaaaaattgt atatgagaga 3360 gacagaacta gacagagaag aaggagaaaa tgtgtcttct ttatacacta ttttgtaact 3420 tgctttatcg agtaggttat gaaaaatctt cctatgtgaa aaacatttct gcatcatttg 3480 aaatgtctat aatatatccc attgtgttta gatacaataa tatttagcca atctctttat 3540 gtgtatatat ttaatacagt cattctataa atattgactg agtagctgct gtgggctact 3600 gtccgcagtg ctgaacaaga caagcatgaa tccatgaaac tgatttcat accagaatat 3660 aaaaaagaaa cttaaagata atcctcatca tggtaaaaga tgaagaacct atttttgccg 3720 ggacatctta ctctttagta attggtggcc agtgttcttt ttcttgcatg ctgttttgga 3780 gagtctgttt tttaaataaa tatttaagta gcctgggcgc agtggctcac gcctatggtt 3840 tcagcacttt gtgaggccga aggggatgga ttgcttgagc ccagggcttc aagaccagcc 3900 tgggcaacct ggcgaaaccc tgcatctact aaaaatacaa aaattagcca ggtatagtgg 3960 cgtgtgcctg tggccccatc tacttgggag gctgaggtgg gaggatccct tgagcctgag 4020 aagtggaggt tgcagtgact gagatggcac cactacactc cagcctgggt gacagagtga 4080 gacctggtct caaaaaataa ataatattt atgtaatcat ctttaagcag tgtttttaat 4140 tttatttatt tatttattta ttttgagac agggtctcac tgtgtcacct aggctagagc 4200 acagctgcat gatcacggcc tattgcagcc tcgacctccc tgggctcagg tgatcctccc 4260 acctcagcct cccaagcagc taggaccaca ggcacacgcc accaggcctg actcattttt 4320 gtattttttg cagagacggg gtcttgctat gttgttcaga cctgtctcaa actcctgggc 4380 tcaagccatc ctcctgcctc ggcctcccat agtgctggga ctaagccatg aaccactgca 4440 cccggcataa gtggtctttc tttaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4500 aaccacatta attaaaatat gtatttgctt attataaata tatttgaaac atgccaattt 4560 ttcttctctt tttttgctct attggtttct gtgtgtggat ggatatattt ttaatggcaa 4620 ataggatgag tgtctttact tccaagtagt cagtgttttt ctttaatgtt tgtactaatt 4680 ttgtcacatt gcagttagag gttgtggcct gtctaatttc tgcttttttg gaacttgaga 4740 gtctctgttt ttatttgttt ttggtagcct ggcatagagt ccatttttct tttcttttct 4800 ttttttgaga cggagtttag ctcttgttgc ccagactggc gtgcagtggc gcaatctcag 4860 ctcactgcaa cctccgcctc ctgggttcaa gcgattctcc tgcctcagtc tccccagtag 4920 ctgggattac aggtgcccac caccacacct ggctattttt tgtattttta gtagagacgg 4980 ggttttgcca tgttggccag gctggtctcg aactcctgat ctcaggtgat ccacccgcct 5040 cggcctccca aagtgctggg attacaggtg tgagccactg cgcccagctg tagatacttt 5100 ttaaaaaggt atagtttctg attatggggt agaaatgtgc tatgtctgtc atttcagcct 5160 tatgaattgc ccagaataag ctagatcacc tttaaggcca tgtggttagg gaaacttggg 5220 cacagaattt acattttcaa cttggtgata agatgggttt aaggtaagaa tcaaatagga 5280 gaaagcctta gctgttccag cggcccatgt ttaaaagaat gtgcttcttt ttccaagtat 5340 ttctgccgct tgcatgcact gagcttcttt ggaaaggagc accatgcagg catattttcc 5400 agacaggacc ggatttgctc gttactcaga ggtgtgtgca ttctttgctt ttaggatatt 5460 taattagcat cttttaatag tgatattacg gtgtcttaaa agtttatgca tttgaaaaga 5520 aaagaactta ctccttgcca ggtctcaacc tatcatggtt atctttgcag ctgagctgcg 5580 ttggttttga ggctcacata tggtaaaagt ggttggaaat ctggaaatat tgctgtgtat 5640 ctgcaaagca gcttgatata gtggaaaagg tattaggtca ttaatcatga gatttggatt 5700 ctagcccctt agctgctgcc tgccaggcct ggagaccttt gttctcttct ttaaactgct 5760 gctttctcat cagaaaatga agttcctctc cataccacct ctctgaaggg ctgtgaagct 5820 cgaagtggca gcttaaaaaa ctgcccatct caggaggtgt cttaagaagg aggacatacc 5880 gctggctcct gccttctca cttagccagg tctgatacct gtgttgtttt cactgtggcc 5940 attttaggat tttcaaagg ctttcagaaa gcaacatgct accgtacccc ttatacacca 6000 aaactggttt tcatttgga atataaaagt gagatttctc caccagtaca ataaagttgt 6060 tacaagtggt tcctatgtgt ttgtttttgt ttttgagaca gagtctcact ctgtcaccca 6120 ggctgcagtg cagtggcaca atcttggctc actgcaacct ccgcctcccg ggttcaagca 6180 attctcccac ctcagcctcc taagtagctg ggactacagg cacccgccac cacgcccagc 6240 taatttttgt atttttagta gagatggagt ttcaccatgt tggccaggct ggttttgaac 6300 ttctgacctc aggtgatcca cctgcttcag cctcccaaag tcttaggatt acaggcgtga 6360 gccaccacac ccggcctcct gtgtgttttg aaggtgattg tgacctcagg ttttggcagg 6420 gctatacctt gtgtttgctc ttactccaac tccatggcat acctggacca ggcctcttca 6480 tcttgaagag ggatctgctg aaatgcaggc ccagtgaatc tccccatgcc tggacacagt 6540 tccgtcaagc caggacccgg tgctgcctgc acccctgttt ctgttagtct gactgtcctc 6600 gctgagtcta actccttgag ggcagagagg atgtcttatt tatttctgcc ccgctagccg 6660 tgtaaactga gtaggtactt gtaaatgttc attgaataag tacctgatta atagaattta 6720 attcaagaag aatgtattga tgggcctgtg tggtcaccac agtactgaga tgtaggtggg 6780 agctggctga agggggaggc acctaaacag gagtgcagac agcggcacct acggatgatg 6840 gcccgctcca tcccaccgca gcgaaattgt cccagacctc tgcagcttcc cccacaccta 6900 gactgagaga gagctcttct tccttctgta gggagcaggt gtttcctcca gatgtccaat 6960 atgtacctcc cattacagcg gtgttaggaa ggtgagggct gccgctgaaa gggtcccctt 7020 cataatcatc actagatttg gggtatatta tggattaaat agaattttta taagatgacc 7080 tgaggatcta tttaaataaa atcctctttc tttctgcaag atcatggatt taaattcaac 7140 acaactgact tcatagggaa ggggtatggt gaaagggaag tgaggtgggc agcactgata 7200 tttaacaagg tgagggtcct tctcctgctc tgactgtcac attaaaatat tcccaggaga 7260 aattggagaa aactcagatg aaatatcgtc tgtgttccag gaggcaggac tcatcggaat 7320 gcttttattt tgctccattt taagagattt gcagataaag aggagtgaag atttctattc 7380 agatttactt gctttatatt ttaacttata gaccacaagc caactttcga aagagcatca 7440 ttttgaatag taagagttag gaaggcaaat acagaaggac taatggcttc caagattatg 7500 agcttcatag gaatggtttg agatgaggct atagtaaagc agaatattga agttccccca 7560 ccccctttca tttttcattt ttcattttta agagtgagcg aggccaggcg tggaggctca 7620 cacctgtaat cccagcactt tgggaggccg aggtgggcag atcacaaggt caggagtttg 7680 agaccagcct ggccatcatg gtgaaaccct gtctctacta aatgtacaaa aattagccag 7740 gcttggtatc aggtgcctgt aatcccagct actcaggagg ctgaggcagg aaaattgctt 7800 gaacccagga gtcggaggtt gcagtgagct gagatcgcac cactgcacat ctcagaaaaa 7860 aaaagagtga ggccccaagt ttttttgcat ttgtttgtaa ctgaatacgt ctgaagttat 7920 gtgataacca cgccaaggtg acaaattgcc aagtttcagt aaaagagacc cagttattta 7980 gaggttgaca cgtggatatg tccctttcta agaagttcgt ggtcagcttt acatgagtat 8040 ttaaatgcgt gtttataatt cagcaatatg gcttgtaaaa tacagattgc caatcaagtg 8100 acatgcaaat cttgatgatc tgaaacaagt tttcttctgt tatctatgga agaaatggta 8160 atagggatat ttaagtggga tgaatttttt gaagcatttt caggcagttt tccacatgga 8220 acaaaataac attgagtggg ctgctaacat gaggaacata ttgccctctg cctaggatta 8280 tgagtaaatt tgataaattc tagactgcag tctcatttta gctcatttta tgaggcagct 8340 tgacaactgg gatagtgtct cttttttttg tcgggggtgt tgaggctgga gtctcgctct 8400 gctgcccagg ctggagtgca ctggcgtgat ctcggctcac tgcaacctct gcctccgggg 8460 ttccagtggt tctcctacct cagcctcctg agaagctggg attgtaggca tgtgccacca 8520 cgcccggcta atttttgtat tttttagtgg agacgggctt tcaccatgtt ggccaggctg 8580 ggtctcaaac tcctgacctg aagtgatctg cccgcctcag ccaccctaag tactgggatt 8640 acaggcatga gccaccacac ctggcttctg ttctatctgt gcattgggga tgaaattaac 8700 acaaatgatg tttaaagaaa aaaatgctca gagaagttag aaatgtgctt taaattggaa 8760 tcatctctta gtatgtaaaa gttttttgta atagaaacaa gcagggcagt atttgacctg 8820 ttgacagtgt ccttggactt tacaatttgt gaagcagcgt attttgcttg agttgtacga 8880 ttgtcgtttt tttcccccca ctttgacaac tgttacagaa cctgtcacca gatacaggca 8940 agggaggttg ggcttcccat ctctgcacgg cttccctgtg attcacaagc aagcaatcag 9000 aagtgcacaa aagtttagaa cgcgattttc attctcttct ttccttagaa aaactcgctt 9060 tgttagcctt ttccagaaag gaaggcactc aattgttgta atactcaaat cataaaaaga 9120 agcctagtct agtctattca gcaaggtgtt ctgaaagagg gaatttttta agttcaatta 9180 tgcgaagatc ttgaaggtgg gactcaaagg agagggctat cctgggaaga aggctttgga 9240 aaatgagagg catgaagggg agagggtatt taaatgtgtt tgaagccaag gatccttgag 9300 agaaaaagct ggcactaaca gcgttcaaag aacttgcgtg acaagtgatg actaatgaca 9360 ctgagggtgg gttgtgggtg cctagtgaat tcctccgaag ccaagagaga ggtttccaga 9420 cccagggaag aaggtgtgta cacccagaag tagtgtaggg acagagattc cgatcacaag 9480 ctgtgactgg aagacgccga ccaccactgc agcagcctga aaaccacagt cttgaaccgc 9540 cagcgaaggg ctgggaagtg cggatccagg gctggtgcac tgaacccaga ggagcaggct 9600 cccattccca gctaagggtg gcagctggcg gggatctttc cagcagaaag ctgtaagtgg 9660 aagctttcaa ttcagagcag tagcaatgcc ttcaaagtcc caggcttcac gtgggaacag 9720 agaatgtgaa gagtatttag caggatgcca atataagaaa tctatattgg tgttcgtttg 9780 tttgtttttg agatggagtc tcgctctgtc acccaggccg gagtgcagtg gtgcgatctc 9840 agctcactgc aatctctgcc tcctgggttc aagcgattct cctgcctcag cctcctacat 9900 agctggtact acaggcacgc gccaccatgc ctggctaaat tgttgtattt ttagtagaga 9960 tggggttca ccacgttggc caggctggtc tcaaactccc ggcctcatga tccgccctct 10020 gcagcctccc aaagtgctgg gattacaggc gtgagccacc gcacctggcc caatattgtt 10080 tgttattta tttcttgaca ggatctcact ctgtcaccag gctggagtgc agtggtgtga 10140 tctcagctca ctgcaacctc caccctctg gctcaagcaa tcctccctcc tcagcctcct 10200 gagcagctgg gactacaggt gcacaccacc acacccaact agattttgtg ttttttgtag 10260 agatggggtt tagccatgtt cagctagtct caaactcctg ggctcaagtg atctgtccgc 10320 cttggcctcc caaagtgttg ggattacagg tgtgattcat gatgtccagc ccagtatttt 10380 tctttcactc tggaaaccaa aaattattgg cttttttcc tgttgcattc cctttactta 10440 gatgaatcta gcaaggttgg ctgttagtgt ctaggtcaga agtctaagtg aaagtgaata 10500 tttaaccaca ctcaagcaca gctgatgatc tttaatacta atagaggtat aagacttaaa 10560 agaaacaaga acccagaggg aaaatatggc catggactca gagaaaacca cggcagcttc 10620 catggactca taaaaagagc tcaaaacta ggaagtggat ggagactctt tttggaatga 10680 atgaattcaa atgtgggctt tcttagtaga ttaaatcatt ttctagaagg aatttcagaa 10740 ggatgtgtgc ccaattatgg tatcaggtct gttgtagact cttcaaggag gaagcctctg 10800 aaagacaaga aggaacaatt aaaattaga attcaggtga gtggatcacg aggtcaagag 10860 atcgagacca gcctggccaa catggtgaaa ccccgtctct actaaaaata caaaatttag 10920 ctgggcatgg tatgctgta gtcccagcta ctcgggaggc tgaggcagga gaatcacttg 10980 aacccgggag gcggaggctg cagtgaacca agattgtgcc actgcactcc agcctggcaa 11040 cagcgagact ccatctcaaa aataataagt aaataaataa ataaataaa attagaactc 11100 agaaaaggaa ttaatttctt ctgagagaga aaaagatgag attctagcct aaggtgtaac 11160 acatccatcc accaggtatc atttttatac acgtgaagtt aaatcaccaa aggaccaggt 11220 gagcagatgt ggactttccg actgtgtgtg tgcgacttcc tcagagccct cagtggcgtt 11280 cccttttccg cgctagcgtt tggtccctgc gctttttctgg atgcccccac cccctctggc 11340 tccacgaggc cccctgtacg tcaccatcac ctttgtgagc ttgaaacctg tcacccaccc 11400 gccttccaga tgtcacctgg gccctcccgg aggccctcgc cctcagtgtg tctgattctg 11460 agctgtcctg cgttttcccc tcccctcacc ctggcgaccc ttttcggtct cagttgccag 11520 cctcctgcta gggctgggtg ggggacatca aaggcaggac aaggtgtagg gtcctcaccc 11580 accacttagc agctctcaga tgcagacaga tttttcagct ggcctgtggc tcagtttccc 11640 tcagctacaa gaggggtgca tgctagggtt tctctggatt gctgcacctg gcaggtagtg 11700 tgagcttggt aggtgcttcc ttgcttatca ttgcctctcc catcttaatg ttgtcccatc 11760 catccaatgt ttatgggatg agaggttgat aggagggcat ggccctgaca ttccagggac 11820 tgaccgacac gctgtctaca caaacccctt ctggttcttc tcgtgcactg ggcgtgccgg 11880 agacacactc ccttaccctc ataccccgcc gcacccctgt gacctctacc tttgagacct 11940 cagcttaaac tcactcttag ggaaggctcc ctgaaccacc tgctggggtt gtatgctgat 12000 gcaggtactt gtaacacctg gtgcttttcc tttcgtgcac tcaggcagtg tttattcaag 12060 tgatggcttg gtgacagtgg ctctccctga gaccccgtga ggccagagtc cttggctcat 12120 cactcatggt tgaacccgga gcctcttgct ggtaggtgct tcaggactgg ctctgggagc 12180 ctgtggctcc tgccgggtac ccaccggttg agatacctca agttttaaat gccacctcct 12240 tcctgaagcc ttccttgctg ctcccccaaa ctagaggcag gagttttgtc cttcagataa 12300 cctatggcat ttgagtcact ctgatttgat gaattctgcc ttcacttgag cagctattag 12360 gggcatatgt cagtcattca ttcctcagtt catgtattta ttcagcaaat atttactgag 12420 cacgtactgc gtgccaggca ctgtcctgct gtggaaaaca gcaggcatga ttccctgcca 12480 ctaccaacca ctgcatcgca taactggcag actcccagct tcaaggagag gcacggaggg 12540 aaactgagag cagcctgcag aggggaaaga gcggggacag agggtcacgg aggtcgcagg 12600 ggcgtgtgtg cagcacctgc cagtgaacgg aatgtgcggc tccagatgtc gttgtcttta 12660 aacttcggaa tttcctttca ctaaagaacc aagtccaggg ggaggaaaga gtgaatacaa 12720 attatccaag aaactcaaga gctcatttta gttctcctga ttatgatctt aaaggcatta 12780 agcgctcaag ttaaactcct tgtgacccac ataggttagc agaatttaaa tcctaggtga 12840 ttattaactc taatcataca tctaatgacc tatattgaag atacactgcc tgcttagttg 12900 tggcttcagc ctttgctccg tcactgatag ttctagcctg aaaagcaaat gagccctcat 12960 gctcacgatt tcaccacagt cacataagcg ggaagagcag gctcctggct gtggcgagct 13020 tgactccatt tggtttgata gaaatgagag gtagatgatt ccctagacaa atgcaggcct 13080 ttctcgaagc ccctttccca ggacgacgtg acatgagtgg tctgtgcctt ccagggcagc 13140 cacgtcatgc tttgcccagc cagggcggtg gggaggggaga cagccacatc ctgcccgggg 13200 ctcctgggcc ccgctgcatc aagtgaaagc agggctggct ccctgatgtc cttggagaag 13260 tcgcccacac tgctttcccc catgggagtg acaaggatgt gtcccgccag ccttccacga 13320 cggacccccc actctctatt aattcccaag aaaccaggcc atggaggtgg gtttgagggt 13380 ttgtattggt gttttttaaa gtcaggttga ccgagtgcgg tggctcacgc ttgtaatccc 13440 agcactttgg gaggctgagg cgggcggatc acatgaggtc aggagttcaa gaccagcctg 13500 gccaacatgg tgaaaccttg tctctactaa aactacaaaa aaaattacct gggcgtggtg 13560 gtgggcgcct gtaatcccag ctactcagga ggctgaggca ggagaaaccc ttgaactagg 13620 gaggctgcag tgagccgaga tcgcgccact ccagcctggg tgacaagagt gagattctgc 13680 ctcaaaataa ataaagtcgg gtttattaag atataattta catacagtaa tttttttttt 13740 ttttgagaca gagtttcact cttgttgccc aggctggagt gcaatggcac gatctcagct 13800 cactgcaacc tccgcttcca gggttcaagc cattctactg cctcagcctc ctgagtagct 13860 gagattacag gtgtccacca ccatgccttg ctaatttttg tatttttagt agagacaggt 13920 tttcgctatg ttggccaagc tggtcttgaa ctcctgacct caggtgatcc gccagcctcg 13980 gcctcccaaa gtgctgggat tacaggcatg agccactgca cccggccagt acatgctttc 14040 ttgatttgtc tgtttcccac ctgtctcccc tccctagaat ggcagctcca tgacgacaga 14100 ggtgtttctc tgttttctcc atggctgcac cctcagctgc tagaaggtgg cccagcatag 14160 gaggtattta atgaagcctt cctctccact taaatctaca cccttgtgct tattaaaagg 14220 tgacagtttt ctgtttgaaa attttattag tgttttaatg agaaagttat tatttgggta 14280 atgcctgaat atgaggaaaa cattaagggt agaaatgtaa ttgttttcct atttcattca 14340 gtctatggat tttattgaag attacagaat tacttctttg tagctatgga agtaaaaaaaa 14400 taataagacg agtagctatt tcaaaacgta gggctgataa atttgggatg gtttgagaac 14460 gttaagttgg ggaactccat ttcttttttt acatttttat ttattttcat ttgtttattt 14520 attatttga gacagagttt cgctctgttg cccaggctag agtgcaatgc catgatctcg 14580 gctcactgca acctctgcct ccggggtata agtgattctc ccatatcagc ctcccgagga 14640 gctgggacta caggcgcctg ccaccacacc tggctaattt ttgtattttt agtagagatg 14700 ggatttggcc atgtcagcca ggctggcctc aaactcctga ccgcaggtga tccgcctgcc 14760 cttggcctcc caaagtgctg ggattacagg tgtgagccac cgcgcccagc cagggaactg 14820 catttctgac agtggctcag tagtttgga gttaactggc aaggtggac agaatcttta 14880 aacatatgtg gaggaattgg agatttaca agatagtgaa gaacgccag gccatggtct 14940 ggagaagatg gaaacttgat gttttggggcc attgtccc tggttgttg gccaatttat 15000 gaaagaagca gttaagagcc tgagtggcac tttgagggg ctagaaggga agaccctggt 15060 aaacatccca aactttggat tgggaccca aaagctcca tcccaggagt acggtgacc 15120 tggaaacgga tcagcgtaat cgaggactga agtccagttc tagctacgcc cagtccttga 15180 gactggatta aggtgatctc agatgcaag gacccaat gcctggcaga agcaagtgaa 15240 tatccttctg gaggaacaga gcctcatcct aggcctta ttatttaa ggacaatttt 15300 tcaatgcag gctttcctcc ctttgcag ttcccttg cataaatttc agtcagtggc 15360 cagctgcagt ggctcatgca tgtaatccca gcgctttggg aggccaggc gggtgaattg 15420 cttgagtctg ggagttggag accggcctgg gcacataga acccatctc tattttaaa 15480 aaaaataat taattatcac tgcttagtta aatttagtg gtctcccac atacagatc 15540 agatcccagc tcccatgta tatacactgt gagtgctgta taagtaca gctctgccgc 15600 cagttctcca gcctacaaat cacagtatag atacagatg tgcatgatga tcactggcca 15660 attgcgtcac ttctccaa gtcagtctgt gattgtccc tgagcatctg tcggtcagtt 15720 tcatgcacag acctgcaaagc atatggtttt gtctactct tgtctctcag tgataaaccc 15780 acatggcatt ttgtaaagt ggatacatca ggccaggtgt ggtggctcat gcctgtaatc 15840 ccagcacttt gggaggctga ggcaggtgga tcatttgggg tcaggttt gagaccagcc 15900 tggccacat ggtgaaaccc catctctact aaaaatacaa aattagctg gatgtggtgg 15960 caggcgcctg taatcccagt tactggggag gctgaggcag gagaattgct tgaacccagg 16020 aggcagagct tgcagtgagc cgagatcatg ccactgcact ctagcctggg tgacagagca 16080 agactaccat ctcaaaaaa aaaaaaaaaaacagtaat caagcatgaa attatgaaa 16140 tgctcagaga taaaatgcgc gaggcctgta cactgtaatc tacaaacac tgctgagaga 16200 aattttaaaa gacctaaata aatggcaagt tatacatgc tctgaatca gagactcag 16260 tatcttagga tggcgacttt tcccaaatg atctacagat tcaagcaat cggaatcaga 16320 cctcagcatg cctacttgta gatttgata acctgattct aaagtttata tggaatgca 16380 aggaacccag agttgctaaa atacttga aaaagaaaa cacagttgaa ggacttagac 16440 tacatttt xtaagcta tactaatca xtagttgg xtagtg 16500 aaaatagacc attagatgaa tggacagaa tagcagtcc agaatagat ccacacatat 16560 atggtcaatt gatttcagc aaagtgccaa gtcatttaag tggggaaag ataatctttt 16620 caacaatga taccggaca actggatagc catatgcaa agaacctca ccttcagctc 16680 acagcactac aactcata tattacat tattatac tattagta tatagtata 16740 tatcatgtta catattatat tatcattat tatcatatatg atactgttat gtcatatat 16800 tattattgaa atgggtcata gatctattg taagagtta aaccatccag gtacagtggc 16860 tcatgcctgt catcttgcac tttgagaggc caaggcgggt ggatcacttg gccccaggag 16920 ttacaagacc atcctgggca acatagcga acaccgtctc tacaaaaaaa tgaaaaaatt agttgagcat gatgacactc acctgtagtc ccagctgcac agtagtctga ggtgggagga 17040. tcacctgagc ccagagaggt caaggttgca gtgagccatg attgcaccac tgcactccag actgggtgac agagagaccg tgtgttaaaa aagagttaa aactataaaa ccttcagaag 17220. aaaacatatg agaaaattct agtgattttgg ggttttggcaa agattccttg aacatgattt 17280. aaaaagcatt aactaggcca ggtatgctgg cttacacctg tcattccaat gctttggggg accgaggtga gaggatagct tgaggccagg agtccgagag cagcctgggc aacataacaa gagtgggtct ttaccaaaaa aaaaaaata aaagcctgtg ccaggcacag tggcacatgt ctgtagtcct agctactcac gaagctgagg caggaggatc acttgagccc aggagttgaa gcttgcagtg aattatgacc atgccactgc actccagcct gggccacaga gtaagactaa 17520 gactcagtct cttaaagaag aaagcgaccg ggcgcagtgg ctcacgcctg taatcccagc actttgggag gctgaagcag gtggatcaca agggcaggag atgaagacca tcctggctaa 17640 cacggtgaaa ccccatctct actaaaaata caaaaatta gccggacgtg gtggtaggcg 17700 cctgtagtcc tagctactcg ggaggctgag gcaggagaat ggcgtgaacc tgggaggcgg 17760 agcttgcagt gagccaagat cgtaccactg cactccagcc tggacaacag agcgagactc 17820 catctcaaaa aaaaaaaaa aaaaaaaaaa aaagaagaaa gcataaacta taaaagaaaa 17880 attaataaa ttagtcatcc tcaaaattag aaacttttac tcatcagaaa acacttaata 17940 aaatgaaaag tcaagccata gacttagaga aaatatttac aaaacatata tctgacaaag 18000 gacttggata tggattatat aaagaactat tgtaattcaa taagatgtca aacaacccaa 18060 ttaaaaatgg gtgaaagatg aactaactct tcaacaatgg gcatgtcatt tgaatggatg 18120 gtaagcaagc acatgaaaag atgttcatgt gccttttccct cattagtcac tagggaaatg 18180 caagttcata gacatctctc ttcgtagaaa gatatcacta cacacccaca agagtggctg 18240 taattaagca gtctgaccaa gtatgcgtaa gaatgtggaa taagaactct catacactgc 18300 tgatgggaat gtaaaatgat agccactttg gaaaacattt tggcaaataa taccacttac 18360 attattcg aaaatattgt atacctgaaa gaactcaaag tgaaaaagct atatactgtc 18420 tgcttccaag gctacacatt atgggaaagg caaaactatg aagacagtaa aaagatgcgc 18480 cagtggttgc caggggctca tggggaggga aagaggaatg aataggtgga acacagggca 18540 tgtttagggc agtgaaacta ttctgtatgg taccgtaacg atgaatacat gttattaggc 18600 atttgtcaat acccataaaa tgtacaacac aaagagtgaa aatgaaaact gtgggcttca 18660 gttagcaata atatgtcaac attggctcat cagtggcaac aaatgtacct caccaatgca 18720 agatgtttgt ttgttgtttg tttgttttgt gacggagggg gtgcagtggc gcaatctcgg 18780 ctcactgcaa gctccgcctc ccgggttcac gccaatctcc tgcttcagcc tccggagtag 18840 ctgggactac aggcgcccgc caccacgccc ggctaattttt ttgtattttt agtagagacg 18900 gggttcacc atgctagcca ggatggtctt gatctcctgc tgtcgtgatc tgcccgcctc 18960 ggcctcccaa agtgctggga ttacaggcat gagccatcac gcccggccac caatgcaaga 19020 tgttaataac agggaactg tggtgggagt gaggtggtat atgagaccctc tctgtacttt 19080 ccactcaattt ttctgtaag cccaaactt ctctaataa gaagtttat taattaaag 19140 ttacttttat agtgtatcta tatctaggaa taatctga aagatatat aagatctcta 19200 ctcagaaaac tgattgtt attagagag cttaaata gcccaataa atgatggat 19260 atactatgtt catggaaggg acagctcagt attaggagg tgtcagtcat cttagaaaaa 19320 gcctcatgtg tcacaagg gatactgaca tctgacacca agcacatgta ggcatcctga 19380 ctacgtttac ttgaatgatg tggactttac agagctgact atagacagtt caaatggcct 19440 gaaaactgtt caatgcactc cctcccaggc tgtcatggga tgcactcag gaactttact 19500 ttttaacaag aaaattcagt ttctctta aacagctggc ttctgttcca ttagcattct 19560 tgtcacttta agttgcattc atctttgttttttttttt gaaaaacatt tgttctgcaa 19620 ccagtcttgt cctttaaata cttgtactgt atacaggctc tttttcatag gtccattact 19680 taaaatgatg taagtgtgtt tttggtggca ggggggtggg agttgtttgt tttgttttgt 19740 tgagacacgg tcttactctg tcacccaggc tggagtgcag tggtgtgatc ttggctcact 19800 cctggcctca agtgatccac ccacctcagc ctcctaagta gctgggacca caggtgtgta 19860 ccaccacacc cagctaattt tttttttttt tttttttttt ttttgtaggg acggggtttt 19920 gtcatatcac ccaggctggt ctcaaactcc tggactcaag ggatcagcct gtctcagcct 19980 cccaaagtgc tgggattaca ggtgtgagcc actgcaccgg tcctgatttg agtttttgta 20040 agacagggaa caatgttcag aatttagcac caatgtcaga ctcattctgt aaatttttat 20100 tgaacgtctg cctggtgtag gagaggaaga tgacagacaa gaattcttcc tccaagagtt 20160 acaggtcagt tgagcagaaa aggcatacat caatacccac aatgagagtt gtcgtgattc 20220 agaggaggga caaagtcctt cccctggagg gatcctgagc actttggaga ggaaaggcat 20280 ctgtactgcc ccccaaatgt gtagaatggg atgcattcct ggcagaaaga agtaggataa 20340 agtacagagg ccagggctgg gtgcagtggt tcacgcctgt aatcccagca ctttggggagg 20400. ccgagacagc agatcacctg aggtcaggag ttcgagacca gcctggtcaa catggcaaaa ccctctctct actaaaata caaaaattag ccaggcacaa tggcaggtac ctgtaatccc agctacttgg gaggctgagg caggagaatt gcttgagccc aggaggcaga gatcgcagtg 20580 agccaagact gcgccactgc actccagcct gggcaacaga gcaagactct gtctcataaa aaaagaaaaa aaaaaagtac agagtccagg aagcctgggg tggggctggc agatgccgag 20700 tcatctattt tggccagagt tcaaggcttg ctaggggaca tgaagagaag attcgtgcat 20760. tctagttcaa actccaccag atatttgagc tccttctctg taccaggcat tgttctaaga tacgtaagtg aacaaaaccc atgacaccct cgtctatgag agctgatcct ctggcaggga 20880 cagacaggtc atgagtggag tgatggagca gctggcctgg tgacttagcc gccttcaggt 20940 acagtaggag gagcaagccc aggacaggtg agtgggtcaa gggtgccaga aggggtgagg gcaccaggaa gctggtccag tttggcttcc ctgaggtggt gaccaggacc tagcatctga 21060 ggaagggctg gaagcaggtg agagcaggtg gagcagacat caggatggga gcatcctgac 21120 agggaggca gcagggtggg ctcatgagag gaacgccag gaagtgtgac tcgagcagtg 21180 tcctggagag gaggagg agaaagaggt caggaggtcc caggggagag gcaggaccag 21240 tctcgtggag gtcggggccg ttgtgaggac tctggtttgt gttgtgtgtg aaaggccatg 21300 ggatggggac cagcgagggc ttcttagggg actggatatg ctctgatcta gctcctaaaa 21360 agcccccttg ggcagcttgc agggcccggg cagaagctat aggtggttct gaggtttgca 21420 gagggggcctg aaggggtggg gcccggccaa gcaaggtggc taagtgggaa aggctccacc 21480 gcgttgggtg taggaagacc ttgaccttag ctccagccca gccactgagc agccgtgtcg 21540 ccttgggtga tacctgtccc tggtcggttt ccctacctgt gaatctgggt acttggaagc 21600 catgctcgag aagagcccat ccccaggagg tgatcagggt tctccttcag gtgaggaacc 21660 tggcagccgt gtgtgagaac cttagaaaag ggagagggaa gaggctgtgg caggagagtga 21720 ggagggagtt agtgataccc tgggcaggat gccatgagct gggatggaaa ccacaggatg 21780 aatgcaagta attaaaaaaa aaaaaaaaaa aaaaacagca ttgggccggg cagtggctca 21840 cgcctgtaat cccagcattt tgggaggccg aggtaggtgg atcacctgaa gtcaggagtt 21900 ggagaccagc ctagccaaca tggtgaaact gaaaatgcaa aaattagcca ggcatggtgg 21960 cgtgtgacta tagttccagc tactcaggag gctgagacag gagaatcact tgaacctggg 22020 aggtggatgt tgctgtgagc tgagatcgtg ccactgcatt gcagcctcgg tgagagagca 22080 aggccccatc tcaaaaaaga aaaaaacaga ctttccgacc aaacgatcga caaaccagac 22140 tgtccaaaca gccataagcc gtaactttgt gcggaggtaa aagaccgagg tcacatcggg 22200 acctgttgga ttcaaggcat gttgacagct gtttccaggc ttcagataga gcctccagct 22260 ggcagggtgg ccacagggct tgttgagtag gaagcctcgt tgctttgaca ggttacttgg 22320 ccccatgagg gacaatccca tagtcagtta cccagaaacg tgactgtctc cttgaaatcc 22380 tcagcatggg gtcttatgaa taaaccctta ctagatttcc tgttctgtct tatttttatg 22440 cagagcttta cttatagca gaaaattcca ttttaccct taaatggctt gcttctgctc 22500 ccttagtgtt cttgtcactt tagttgcat tcatctttgt cccttagaa aaggatttgt 22560 cctgcaacca gctcttgcag aaggtacttg gttattgtt aaccgatgtt tgctaaatgt 22620 ttgaattatg ttgagttgct taaagtcatg ctatcgggta gatgttgtgg ctgttcttt 22680 cactctctta tttggggatt tacaaaacag tttgttttt agttttcttt tatttgttgt 22740 gttgaatagg aatgtagctc tgggaacctc tagttccaaa taagaaagcc ttggacacat 22800 ttccagttgg caagctggca aaatgaaggg cgtacaagtt gttagagagg ctgggagcct 22860 atttaagcac ccagcttcag gatgggacat gggatatacc tcgagttaga ggttcttatt 22920 aactgtggat tcttctatgc agatatctgt cacaatataa gttactataa gtcagtacta 22980 aggcagctgc tacattctgt ttgccaaggg gaagaagaaa gcttggaaat ggtattcctt 23040 aaaaatgtca gtatcataaa agacaaagaa aagctgcgga aatgtttcag attaaaagag 23100 agaagacaat aaatgtaat acctgactct gaacagcatc cagtactgaa ggaggaaaaa 23160 tgctatcaag gatattg ggtcaatcaa CAAatttga atacgaatca tagattgaac 23220 tgtatctgtt aattacag aagcgaagtg ttctgtggtg tgtaggagca cactgccatt 23280 cttagcaaac gtgtagttta gtatttagga gaaagggcca tgaggcatgc aactcaccct 23340 catacaca cacacataca catatataca catacaca taaagaaga attatgggc 23400 taggtgcagt gggctcatgcc tgtaatccca gcactttggg aggccgaggt gggtggattg 23460 tgaggtcagg agatcgagac cctctctact aaatacaaa gattagctg gggcgtggtgg 23520 tgcacgtctg tagtcccagc tactcgggag gctgaggcag gagaattgct tgaacccagg 23580 aggcagaggt tacagtgagc cgagattgca ccactgcact gcagcctggc aacagagcaa 23640 gactctgtct tgaaaaagg aaaaaga gagagaga gagagaaa 23700 Gaaaaaaaaaaaaaaaaaaaaaaaggta 23760 aagcagatgg ttaagttggt aactaccagt gaatatgggt aaagttagga tgttctttac 23820 tctgttttgg gggtgcaact tttctataag tgaaagtact tccaaataaa aagttaaaag 23880 gcaagcaaat aaataaaaga gacagtttct atgttatata tcctagctat gtttaccatg 23940 tctggattct gaaagctgca gagcagaaaa cctgaagaac agatcacctg ttcttaaaat 24000 accactgttg gccagacata gtaactcact cctgtaatcc cagcactttg ggaagccgag 24060 gtgggaggat cacctgagct caggagtttg agaacagcct gggaaacata gtgagaccct 24120 gtctctacaa aaatttaaaa aattatccag gcatcatggt tcgtgcctgt agtcctagct 24180 actcaggagg ctgaggtagg aggattgctt gagcctggga gttcgaggct gcagtgaacc 24240 atgatcacac taaagcactc tagcctgggc aacagagcaa gaccctgtat caaaaaaaca 24300 atcaaacaaa aaatcactcc taattttcct cccttttagt acttttaaaa attaacttaa 24360 aacatttttt ggataattgt agtttttttt actttttttt ttttgagaca gagtctcatt 24420 ctgtcaccca ggctggagtg tactggtgca atctcaggtg actgcaacct ctgtctcctg 24480 gattcaagtg attctcctgc ctcagcctcc tgagtagctg ggttcatagg cgtgcaccac 24540 acctggctcg tttttatatt tttagtagag atggggtttc accttgttgg ccaggctggt 24600 ctcagattcc tgacttcaag tgatctgccc gccttggcct cacgtgcagt tttaggaaat 24660 aatacagaga tccccagcac tctttccagt tttccccaag ggtaacatct tgcaaagtga 24720 gaggacgata tcacagtcag gatactgaca ttgataccat caagatacat aatgtttcca 24780 tcaccaatca gtggtcatgg tgccttttat agccaaaccc acttctctcc taccttccca 24840 tccctttttt aattttgcca gtcattaatc tgttgcccat ttctgtcatt ttatgaatgt 24900 cacataggcc gggcgcggtg gctcacgcct gtaatcccag cactttggga ggccgaggca 24960 ggcggatcac gaggtcagga gatcgagacc atcctggcta acatggtgaa accccatctc 25020 tactaaaaaa tacaaaaaat tagccaagcg tggtggcggg cgcctgtagt cccagctact 25080 cgggaggctg aggcaggaga atggtgtgga cccgggagac ggagcttgta gtgagctgaa 25140 atcacaccac tgcactccag actgggtgac aaagcgagac tccatcttaa aaaaaaaaaa 25200 aaaagaatgt cacataatga atcatatggc atataccgt tgagactca gggtaattct 25260 catgagactc atccagcttg ttggtgcatc aacagtttat tccttttat tgctgagtaa 25320 tttccatggt atggaggac catggtttaa ctattcaccc attggaggac atctaggttg 25380 tttccagctt ggagttatta tgataaagc tgctgtgaac atttgtgtac aggttttcttg 25440 gttttctgt ttgttttaaa cagttctagc caggcacggt ggctcacacc tgtaatccta 25500 acacttggaa ggctgaggta ggaggactgc ttgatcctag gaggcagagg ttgcaggag 25560 ccgaaattgt gccactgtac tccagcctgg gcaacatagc agaccctgt cattcatagg 25620 taggtggatg gatggatgga cggacggaca gatagatagg taggaatgta aattacagggg 25680 ctacgctcag tggctcatgc ctgtaatctc agcactttgg gaggcgaagg cgggcggatc 25740 accagaggtc agcagttttga gaccagcctg gccacatgg caaacccca tcttactaa 25800 aaatacaaaa attagccaag catgctggca tgtgcctgca atcccagcta ctttggaggc 25860 tgaggcagga gaatcacttg aacccaggag gcggaggtta caatgagcca agatcatgcc 25920 actgcactcc agcctgggcc acagagtgag actccgtatc agtactttct ttttattgtt 25980 tttctgttat tatagtttaa gttcattgtt attagattat atactctgta tggcttcaat 26040 tcttttaaat ttgttgaggt ttgtttaatg gtcaaagaca tggtctgtct aggtgaatgt 26100 tccatgggct tttagggaaa aaagtatatt ctagtgttgt tgaatggtgt cttagtccat 26160 tcaagctgct ataacaaaat accgtaaact gggtgattta taaacaacag aaatttttct 26220 ctcacagttc tggaggctgg gaagttcaag atcaaagtgc cagcagattc agtgtcatgt 26280 gaggacgtgc ttcctgcttc atagataaga ggtacataca cgtttaggag catcgtgtct 26340 tcctggtgga tgaattctgt tatcattagg tgatcctttg agcactttta aaaagaatct 26400 gttggccggg cgcagtggct cacgcctgta atcccaggac tttggggggc caaggcgggc 26460 agatcacgag gttaggagat tgagaccatc ctggctaaca cagtgaaacc ctgtctctac 26520 tacaaataca aaaaaattag ccggcatgg tggcaggcgc ctgtagtccc agctactcag 26580 gaggctgagg caggagaatg gcgtgacac aggaggcaga gcttgcagtg agccagatc 26640 acgccactgc actccagcct gggcacaaa gtgagaccct gtctcaaaa aaaataa 26700 aaaataa aaatctgt ttaatagcct actagtgttc ttcctttact attttattga 26760 gcattaatta atcccacat tatgtctatg tcaggactga tgacaatatt tgtataaaa 26820 atttgaggt ctcagaggct gaggcaggag atgcttga tccaggaggc agaggttgca 26880 gtgagctgag accgtgccac tgcactccag cctgggcaac agacagac tccatctcaa 26940 aaaaaaaaa aaaaaaaatcg atgtatcat atcctccagg attcaagtg aacttcaac 27000 agtcttatgt agtctaaatt ttggaatgca tcccagtatt gagttgcagc agggatttga 27060 gtttttgtga agagagagag gtatatcaga atcttgggca taaactaagg agccatgtca 27120 gaacctcagg tgtatgccaa tgagatagat cagaacctca ggcatgtacc cgatgagaca 27180 gatcagaacc tcaggcgtgt acccggtgag acggtcaga acctcaagcg tgtacctgtt 27240 gagacaggtc agaacctcag gcgtgtagcc agtgagacag gtcagaacct caggtgtgta 27300 cccagtgaga cagatgagaa cctcaggtgt gtaaccagtg agatatatca gatcttggg 27360 tattaccca aagaggtata gcagagtctc aggtatatac tcaagaggc atatcttgag 27420 gctttaagta tctagctaag gatttatatc aggatctcag gttataccc agggaggtat 27480 agcagaattt ggggtataga tctaggagg tctatcagtc tegagcatat agccaaggaa 27540 ctatatcaga acctcaggca cctaccaa gaggcatttt aggactcgta aggaggggt 27600 agatttcaa agtgtagtct aacagtttat ctactttgaa atttaaaaca atttaaagg 27660 aaaacatgaa atatttctat ctgtcagaag gtgacatgag ttttaaacaa ttaagaata 27720 tactggctgt ggccttgtaa ccaattatt atgcctatag aattacaga ctccatttc 27780 caggatagaa taacagggac tgacttacct tctcatctga gatacaaaa cctccataca 27840 atacatgaa acatgttct tcaatgct ggacatcagg cagtgaaggg cactgatggt 27900 tgtaagacaa ggtgagaggt gtggcttgag agagtttcca ggttgcagtg cagggagagg 27960 ggaaactgag gcagatcttg gcagacttcc tcagttgaca aatagagct gagagtccag 28020 ggagaccatg gtgtatagat tatccaaagc aaagtatgag aggtgcaagc catatacaga 28080 gggactccag agatctacca aagtacttct tggtgcatcc atatgagcaa aactacttga 28140 ggccaggaaa agaaccatct gagaggatta gaaggaacag tgcccagtac ttgtgccagc 28200 caggaatggt gcctgatact cacgcagggc caggaacagt gcagggatgt gagtgtttgt 28260 taggagaggg aggtatatca gaatcttggg cataaagaca agaaaccata tcagaacatc 28320 aggtgtgtac caatgagata gatcagaatc tcgggtgtat acacagtgag atagatcaga 28380 atctcagatg tgtacacagt gaagcagatc agaatctcag atgtatacac agtgagatag 28440 attggaatct caggtatgta cccagtgagt ccaagagcat ggtgctggca tccggtgagg 28500 gccttcctgc tggatcgtga catgaagcaa ggcaaagagc ctgtcagctc agggctctct 28560 tccttctt ataaagtcac cagtcctatc atgggggccc caccctgatg atcttataat 28620 cctaattacc tcccaaggc taccttcaa tgctatcac attgaattt ggactaag 28680 tttccagcac atgaatttg ggggatacat tcaagtata gcaatatta catcatacc 28740 agtaggattc atcccaggaa atgccaatg gcttgaat at caaaattaa tgtaactcat 28800 cgtattaaca ggatgaaaaa gaaaaaccat gtgatcatct tagtagatgc agaaaagcag 28860 ttgattaaat cccacattca tttctactt aaaaaaacaa ctggattg acagaggtgc 28920 aaaggcaatt tggtagagaa aggacagtct ttcataaa tggtgctggt gcaatggtta 28980 tccatatgcc caaatgaac tttgaccat gcctcatgcc atacacaaa attackcaa 29040 atagatcag agatctgaag gtaaaattta aaactataaa acttctagaa gaaacacag 29100 gagaaaaatc ttgtgacct tggtctaggc aagatttca tagatatgac accgagaaca 29160 caatctatga aaaaaaaa tcaataatt gaacttcatc aaaatgaac tttactgtt 29220 caaagacag ttttagga atgaaacac aagttacaca ttgggagaa atattcgaaa 29280 agcatttgcc tgataaggt attgtagctg gagacagaa aaattctca aaactcacct 29340 agagaaaat aaccagtttt taaaaatgggg caagagatct gaacaac attgtcaag 29400 aagatagatg atagcaagt aaagcatgtga aaattctca atgttatcag tcatcagagc 29460 aatgcagatg aacctacag tcccatgct aatgttctac aacttacaca gtggtggtat 29520 gataccacta catgcccatt tgaatggcca aaattagaaa ggttgaccat accaaacatt 29580 agccatgatg tgcaggact agaacctca tctttgctga caggaggta aaatgataca 29640 aacacattga aaaacaggtt ggcagttgct tttttttttttgagatgg agtcttgctc 29700 tcccaggctg gagtacagtg gcgcgatctc agctcactgc aacctctgcc tcccaatgaa 29760 ttagaaaaat adaaaaag gtaaaaaaag cagtaaaaata atgaagtttt 29820 ctttaataaa aatgctgttt aggcccagac tgaaggctt tagtacca ctcccccact 29880 gagttagag ttaagaaga atattaattt tccttgtgtg aaacattaat cttatcttagc 29940 ctccatgtat ttgtaagtt ctgtaaattc ctgttttccc tgcacagctg caagttcaca 30000 aggcagataa gcttaagctg caaaacatgt ttttcttaag atgtaaggca tgtcacaaga 30060 atatcacaag atgataacgg cctttattct cacttctgta tgcctgcttc ctgcctcaca 30120 tatttcctgc ctcaagatgc gtaaaaaggta cttgccttct ttgtttggtg ctctgacttt 30180 ctggatgcaa gtccactgag ccagtgtaca ccttaaataa atcctcctga accccacatcaa 30240 tcgctccagt tctctgattt cccactacat tttctgggg ctcgtccggg attggagatg 30300 gcagattttc tgtctccctt gcctgtggaa ctggagcccg ggtcgaggga gacctgggac 30360 ctttggtgcc aatgggagga ctttagcccg gaaggagat tggctctcct gcatcccggt 30420 gtccttccta gacaggcaa cggaacctat aaaggggttg caggacggtt ccagcagggg 30480 ctggggatgg tgagagtagc tcactgattc agatgacagg gttttgccat gttgcccaga 30540 cccagagggg ctggggacag tgagagtagc tcactgattc agatgaaact tacaccttag 30600 ccgatgcagg acacgagagt ggctcactaa gttggtcagg aaagaaactg aaaatgggaa 30660 gagtggcttc ctgccttgac taggatcgg gaactgggag cggggaggtg tgtgaaagag 30720 atggttccgg gagggccgtg atgtggggag acacagatct cttagcacgg actgtgtgct 30780 ctgaggcgag tgtgtgattg accagaacca gggcatcaca tacagctgac aggagctgcc 30840 ccacagctgc agcaggctgt ggcaggaata aggtactctc ctagctaagc agcacctgaa 30900 acttccgtaa taggacccag tctggtcagt ctgggaacgaa agtgagagtg agtgtgcatc 30960 acaaagggcg ggatgggagg aaaagcatcg aaacccactc ctctggggtg catgttaaag 31020 aattttaaga aaggttttgc tggagattat ggaattaagt tgtcccccccc aaagattgag 31080 ggttctgtgt gaagtggaat ggccttcttt taatgtcggg tggccagccg agggtacaat 31140 aaatagggaa atgattggtc atatatttag ggtagtgact ggggttggag gacaccctgg 31200 gcatccagat cagttcccat acatcaattc ctggatgatc acagtctaga catgccccaa 31260 atggttacag ccttgtctgg caacttactg taagactcta gtgacctgag ccgaacctaa 31320 ggcagttaga gggcccccctt caccagacac ctcaggtgga aagaaaaagc cacaggaaaa 31380 ttaggaaaga cctgttctac ttcactggga tcaagtgat ctcctgccctc agcctcctga 31440 gtagctggga gtacggggtgt gcaccaccac gcctggctaa ttttttaa ttttatttt 31500 agtagagacg gggttttgcc acattggcca ggctggtctt gaactcctga cctcagacag 31560 tctgcctgcc ttggcctccc aaagtgctgg gattacaggt gtgaaccacc atgcccagcc 31620 agcagtttct tataaagtta aaccaatgcc taccatgaga tctggcaatc ccactcctaa 31680 gtatttggcc aagaaaaag aaagcatata ttccatacag agtctagtcc tgaatgtcta 31740 tagctgcttt attatata gctcagactt ggaaaccatt cagatgccat tataggtga 31800 atatattctc aactgtggt tatccataca atggagtatt actttgcaat caaaggaat 31860 ggcctatgaa tacccataac aacatggatg atgctgaaa taattgtgct gagtaaaga 31920 agacaggaaa aaagtata atacatactg cttgattcta ttgtataaa actagaaagt 31980 aaactaat ctgtaatgac aggaagcaga ccagtgacag tggcatgga ggggcaagg 32040 ggagagatta gatgggcaca ggagagcttt gaggatgatg ggtctgcgta ctgtctcggc 32100 tatgatagtg gtttcacagg ttgatacata cggcaaaaa taccaaattt gtacacttta 32160 atatgtaca gattattgta tgccagttac atgtccataa agctttcttt tgttgttttg 32220 tttttttt atttttg acagagtctc gctccatcgt ccaggctgga gtgcaatggc 32280 accgtctcag agcactgtaa cctccgccctc ccgggttcaa gcgattctca tgcctcagcc 32340 tcccagtag ctgagactac aggcatacgc caccatgccc agctatttt tctattttta 32400 gtaaagacag gttttcgcca tgattgccag gctgtcttg aactcctgac ctcaggtgat 32460 caccccacct cggcctccca aagtgttgggg attackaggca tgagccacag caccggggcccc 32520 aaagctgt cttttaaatg aaaaaagtt gtcttgaat aagcattaga actgtggctt 32580 tggctctgaa atcctcatct gaggacccac actcgggtgc cccaatgtgg cggtgcttac 32640 agaaatgact ccacactgcta aatgagtaa tgggtaattc tccactgaac accactcgt 32700 tagcagcat aagcagcaag agttcaggta atcctcacat tgcaatttgt cattagttta 32760 aacttccagt ctttgtttta aaaacacatt agaataatac tacattttcc ctcatctcta 32820 aacttgactg aagactccaa gagagagtaa tattcatcaa gaggatcatc tactcaacac 32880 agataaactg ggaaagaaaa ataacttgtg agtaattcag aatctggatt atcaggtcag 32940 gctcaatggc tcacgccagt agtcccagca ctttgcgggg cccaggaggg cagatcactt 33000 gagttcagga gtttgagacc agcctgggca acatggcgaa accctgtcta tacaaaaaat 33060 agaaaaatta gccaggcatg gtggcatgtg cctgtagtcc cagttacccg ggaggctgag 33120 gtgggaggat cacttgagcc tgggaggtcg atattgcagt gagctgtaat tgcaccatgc 33180 actccagcct gggtgaaaga aggaaactct gtgtccaaaa caaaacaaaa caaaacaaaa 33240 aaagctaaat tatcaaatgt ctagatcgtt gatggttgga agtaaagttg agaaatgttc 33300 acactgggag atgacacaca gtaaaccaca cagagggttc taacgtggtt gttagaagca 33360 gaaactagag gcttgctgcc tgaggtcaaa ccccggtccc ggtggttctg tgccccagcg 33420 catgttgtgg tagcctctct gtacttcagt ttcctcatct gtaaagtaaa catatgata atgcctgcct catggggttg ctgttaccag gaagtgagtt aatgcacatt aggttcttat 33540. ttatgacagt gcctggcata ggataagggc tcaaaaagtg ttagctgga ctactatcat 33660. tctcaacatc tctaatttat tgcagggttg gatctgaaaa atggctgatg atgatttgat gatgacttca ttttataaa acaataatat tgcagtgcaa attack agcaacctgc 33780. aaccgccac tgcaagttgg atgtctagaa aaggtgccat gagttacctt ctaaaacatc 33840. ataagaacc atgttcacca ataattacca taaggaga gaagtaccaa gtaccatggg gagacagagt ccagaatctc gagagagac acagttacct tttagttaca ctaatgggga aaacaggagc tttgctaccc ttgcacctga tggagggctt ctctgaat agggctatgg ggtcagaagc cagtttcctc ccatatttag aaggtttcca actgttatct ttcacttccc atgttgctgt tggaaaatcc aaaagtattc tattttggcca ggcacagtgg ctcacacctg taatcccagc aatttggggag gccgagatta cctgaggtcg gaagttcaag accagcctgg ccaatatggc aaaacctctt ctctacaaaa aatacaaaaa ttagccaggc gtggtggcgc 34200 acgcctgtag taccagctat tcgggaggct gaggcacgag aattgcttta acctgggagg 34260 tggaggttgc agtgagctga gattgtgtca ctgcactcca gcctacgcga cagagcaaga 34320 ctccgtctca aaaaacaaaa aaagtattct gttggatcgt ttgtgtgcga cgtgtttttc 34380 cctctcagaa agctcgtagg gtcttctctt tgtctccagc atggtctgga atttcccagt 34440 gagtgaccat ctgtgtgtgt gtattcatcc attccatgga gtccctgctg ggcccttgca 34500 atctggaaat tcatgcccat catttctgag aagttatcct gaacgtactg gttggtggtt 34560 tcctgtgctc catgttcttg cttcctgctc ttcggagctc ctgttatttg gttgagtttt 34620 gtctcctgga ctggtcctct cttacttctc ttgcttctcc catgttccat ctgttttcac 34680 tctactttct gtgagatcag gccctttatc ttccaaccct tctattaggt ttgcaattga 34740 gtttgtaatt ccctagaaaa gttcttattc tctgaatatc ccttttgata gcatactctt 34800 cctttttcat gagtgcagtg ttctgcatg gctctcatca gaacatgcta gtgtctccca 34860 tttctcataa ctttctagag tgaggaccat tgaacttgg agtgccctca tttaaaact 34920 ctgtggttga ccttgttccc ctcttttgct gctgctttc accagacttt gagaagcag 34980 aagtacattc agaacttgtc tgctggca aaagacaata ctgttggctt atctaaaaa 35040 ttgagaga aagctcagg aggaagtttt aaaaaatac cacctctggc tgggcgcggt 35100 ggctcacatc tgtaatcca gcactttggg aggctgaggc aggtca cctgaggtca 35160 ggagttcaag accagcctgg ccacatggt gaaaccccgt cttactaaa atacaaaaa 35220 ttagccaggt atggtggcag ccgcctgtaa ttccagctac tcgggaggct gaggcaggag 35280 aatcacttga acccaggagg cagaggttgt ggtgagccaa gatcacgcca ctacactaca 35340 gcctgggtga caagtgaga ctccgtctcc aaaaaaaaa aaaaaaaaaatatatata 35400 father father father father father calf aaccttcagc atataggact attgcagaag ggattatctt ttacttggt tggttctct tggtcttgag 35520 caaattttga cttccctgag ttggccccta aaagttaaag ggaaagggcc ttttctcttt 35580 cctttaaaac caatatggca tatttgctga gaacttagat accacaggat tggcagtgta 35640 gacttacatt catagaccgg atgccatcag ccaaccttga gtaatttgca gcacactgca 35700 tcattttat taagtaatgc gaagtccttg acatgtctca gacattgtct tggttacttg 35760 taaggtctca cataaatcta attttcctct ttctctgccc tttctggttc agctcagttt 35820 attcaagggt gtatttgtgc aacacacttg aataaggtgt ggtcccgcct ttgtagatgt 35880 tatagtttgg gaagaccagc cgggcagaga gaagagcatg attcaaggat gaaggcgtgg 35940 gctggggcc gagggagcaa ggattcccag taacgaggga ggaaggagca gcaccatgtg 36000 cccattactc tatagacatc tcgaaccacc tggccatgta gctgtcatta acctaaattt 36060 acagttattg aaactgaggt tcagccaggc gtagtggctc acgcctgaac acaggaggcg 36120 gaggttgcag tgagccgaga tcacgccact gcactccagg ctaggtgaga gagcgagact 36180 ctgtctcaaa aaaaataaat aaataaaaga aaagaacaaa actgaggttc aaagaaatgt 36240 acagtgctcc cccccttatc caaagaggat acactccaag cccccacagt ggatacctga 36300 agcctcagat agtatcaagc cctatatatg ctatgttttt tccctgtata tgcataccta 36360 tgataaagtt tataaattag gcacagtagg agactaacaa caatgataat aaaatggaac 36420 aattataaca tacactgtaa caaaagggtc tcttcctctc tctctcagaa tatcttattg 36480 tactgtactg ggggtaacta aaaccaagga aagtgaaacc atggataagg gatatctact 36540 gtataaggtg gagttttcaa ggtcatagca ctgccttccc ctgaggttgg cctgcagcc 36600 tctctaggca ctgctgctgc tgctaagaac ccctgtgagg tgaacactgt aagcatcatc 36660 attgcttctc agaagaggag acctggctta cagaggtcaa gcctcaggta ccttaaacac 36720 cattttaaaa ctgaactcat ggccaggtgc attggctcat gcctgtaatc cctctctcc 36780 atgctcaaaa cctgccctcc ttgtctttat attccaaatt tcgtgggtgc cacctcctct 36840 gcccagtgac ttaagccaga gcatacattc atcctagact ctgtcccagg tccctggtcc 36900 aggcagctgc cagttgtcag gatcagctct ttatctcgca gtcctcctgc ctcttgtgtc 36960 attacccagg gctgtcacca tctttctttg ggacagttac aacagccccg taaggagttg 37020 tgctgcttct agtcttgttc cctttgaatc tggattcctt cttgccatca agacaatcct 37080 gatacaaatc tgatcacgtc acacttccct tcaatagtct tccatggctc cttattgttt 37140 taggatgaaa tccaaactcc taaacatggg gattaacaat gtgccatgat tggcactgct 37200 ggcctctcct acctctgcag actcacctct tgccacttct cccttgaggt agatcaaaaa 37260 tggtcacaag ttctttgagg ctcttcccat caagaggtag agtttatttc cccacctct 37320 ggatctggct tgccttgtga cttgctttga cccacagaac gtaacagaaa ggacactgcc 37380 taacttacaa atgaggtcta ccttaagagg ctttgcagat tccacattca acctcttgga 37440 atgctgccac catctgagaa gcctgaggtg gcctctgtga ggatgaaaga cttcatggtg 37500 agaaatacct agcgaacagc ctggcaccag ctaccaggca tgtgactgag gccatccagc 37560 catagctgag ccacaaaatg accacagcta tgtgaattat cccaggtcag accagtagaa 37620 gagccacctg gctgagctca gcccaatttg ctgacccata gaattgtgaa caaataaaat 37680 ggttgtagtt ataagccatt aagtttcaga gtttgttaca cggtaacatg taactgatac 37740 aactcttgga gccagttgtt cagccattct caaccactta ttcaatgatg ttttgggcca 37800 tatatgcaga tatgctgttc ccttttcctt gaaatggccc ttaccctcct ttctgttggg 37860 ttttcctatg gaatatccag tcagccttta ggattcatct tgggtgtccc ttcctgtatg 37920 taggctccct ggccctccag gattccccca gtaacagccc tcatcatgct gcctttgcaa 37980 ccatttgttt atttgtacct ctcacctgct agttgggcaa gttactcact tctctcaacc 38040 tctgcattt tcttcttat aaatgggacc aataatacct accctgccct ggcgtggata 38100 gattaaagaa aaaaaataca tgcagctgcc attgagggcc tggcccacgt gtgatgttca 38160 ataatattat ttctccttgt tttccttccc gtgccagtgc cacacccccc tgtcccagtg 38220 cactggggct gtggatccct tcaaagctga gattgcctgt ctgtggtctc cagcgttaag 38280 cacagtcatt agctcaggtg cgtactcatg tgttccacga gttcaagcct cagccctgta 38340 aagtttgcct gccgtgtatc tgatatattt ctgctaaaac ccattaggcc tttcttgctc 38400 tgaaatgtca tcgttagttg tgtgtcactt cagttttgta actggccagg ccactgcgcc 38460 caggctgctt cctcgtcatc tggctgctaa atgcttcaac cttacctgcc ttgctatgcg 38520 tcccatcctg tatcaggtca gagctcttga gtggtgaata caaatttcat ttcagttgac 38580 ttttgattct tgtggcaggc ctctcggcct actctaattt gattgcaacg gacacaaaat 38640 gtgtccaaac ttgcagcttt tcttctctta ttttgatatc accatccaca aaggtaagat 38700 attttaaagc aataactaca aactttctga aaattatgaa gaagtgctgg gttttaaatg 38760 gaagtcatat agtgtgaact ttgtgtaaag tccgtaggga gttttcttgg aaatggctgg 38820 gaacattctt tttgcacctt tgaagataaa ggtaggtgga ggagctcaca gctcttgtgc 38880 catgttgggc ttgtcactct tgtttatgtg ccaaattctt ttgattacaa aattttaagt 38940 ttaatgcttt aggtattgtt gggcaagatc tagttaatc tagttaaatg tagtagtat gcaaactatt tatgatgtat ttgatttaaa ttcattaaga taggtgtct ttaccaccat tatagtctgg tccttttcct tctgttttaa atgtgtttcc attggcattt tctaaactga 39180. ctttgttagc gtgttaatca tttggcactg gtaatgatta atctttctt tctttctatt ttttttcttt tttttttttg agacagagtc ttgctctgtc accaggctgg agtgcagtgg 39240 cgcagtctca gctcactgca acctccgcct cccaggttca agtgattctc ctgcctcagc ctcccaagta gctagggact acaggcacgt gccaccacgc ccagctaatt tttgtatttt 39360. 39420. ggggtttcac catgttggcc aggatggtct cagcctcttg acctcgtgat ccgcccacct cggcctccca aagtgctggg attack tgagcgactg cgcccagccg 39480 tgttcatcta tttctgtgaa ccgatgctag gtgaaggtac agagggcttt ctagcttctg ggtttgttta ttctgaaatg ttattttaaa tcttagccca acaaattgag cgaaaagact tctagatgtt father ttcaaaaaat father ggtgataat tagtggt gggaaagaga aaaatctgtc ttctgatggt cacctgcccc agcaacacta ctcgtttgag 39720 aagacttcca tcctttaccc tcaaagtgtt ccatgaggtt ggatcagaca tcatttagca 39780 aagaaagatg taaatagatt tctgtagggt ggcattatta agcatattaa gtggttacaa 39840 tacagtaaat tagagggagt agtacagaag cataagcagt caaaaaagtg aaagtctaac 39900 gttcgtaatt attgttctgg aggcttttgt atcacatata agttccaggc tgggtatgat 39960 ggctcacacc agtaatccca acacttagag gccaagccgc gtggatcgct tgagcccagg 40020 agttcgagac caggctgggc aacatagtga aacctatctc tacaaaaata caaaaattag 40080 ctgggggtgg tggcagcgcc tgtagtccaa accacttggg agcctgaggt gagaggatca 40140 cctgggcccg ggagatcaag gctgcggtga gccatgatct tgccattgca ctccagcctg 40200 agtgacagag agagactctg tctcaaaaat aaaaaagttt tgagtgtgaa aattcaagct 40260 caattccatt tgttggttgt cttgagtgtc tgatcacata gaatataaag atgttttgat 40320 agttgggaca gtattcagct acctgctatt father tttcagaaaa father gggggctggg cacagtggct catgcctgta atcccagcac tttggggaggc cgaggtgggc 40440 ggattacctg aggtcaggtg ttcaaaacca gcctggcca acatggtga accacatctc tactaaatat acaaaaaatt agccggggcgt ggtggtgtgt gcctgtagtc ccagctactc 40560 aggaggctga ggcacgagaa tcgcttgaac ccggggaggcg tggggttgca gtgagccgag attgcacaac tgcactccag cctgggtgac agagtgagac tgcatctata aaaacaacaa 40740. 40740. 40740. 40740. 40740. 40740. 40740. 40740. 40740 ggtgcacacg tgggtgagac acggcagctg ctctccagaa gcccacagtg gaggggtttc 40800. ccttcggtct ccttttattc caagcaagtg gcaaaactac tttactctta atacaaacca cttcctttta tcacaggacg cttcccaagc tctgcaactg ttgctcctga ggaagggagt ggaactgata atctgttcct ccctattgtg ttcagtatgg tttttttttt ttttttcctt 40980 ttgctggctt tgttttcctg tccctgtgat gattaaaatt cactctgcaa attagatcac cttcccacg cagagtccct ttgacttctg ttctagatat ccattacatt tttgtagtct 41100 tcggacacac tgtgtgtgcc gctttgccct ctgggtgaca gcaggctgtg gctgcggcga 41160 cagagctgag gtgaattctc acagaccatc actgggttac tcctggagta agtaattccc 41220 aagagctcct tctgtgcaga tcgttagaaa tagatattga ggccaggcgc ggtggctcat 41280 gcctgtaatc ccagcacttt gggaggctga ggcgggcaga tcacgaggtc aagagatcaa 41340 gaccatcctg gccaacatgg tgaaaccttg tctctactaa aaatacaaaa gtagccgggc 41400 gtggtggcgc acgcccgtag tcccagctac tcaggaggct gaggcaggag aatcacttga 41460 acccgtgaaa cggaagttgc ggtgagccga gatcacgcca ctgtactcca gcctggtgac 41520 agagtgagac tccatctcaa aaaaaagaga aagaaagaaa tagacattga acacctgcta 41580 cacagcaggg attgtgctag aagtatggat gcaaagatta ggtgaatatg ttccctagcc 41640 tcacaaagca tacagtctag taggagagac agacacgtaa aaagtttcaa cagcacagat 41700 aatcagggct acaccagaat tgggcccaag atgctgcagg aatctatagg tgaatgggtt 41760 tcatgaagga agagctctt ctcccattta taaccattt tagcctaatc ttccaacag 41820 tcacgcatct agagcaggt gatgcagaaa ataccctcgt gttagttatg aattaccgtt 41880 ggaatccttc cagtgtttgc acctgccctg tgctcgggta actaaaaca gtgatataat 41940 ttgatgtcta cttccctcttg tatttgtctg tttaagtg ttctacaatt ttcatatact 42000 ctgtttcatc gttctcaag gatatttg attgaataat gtttagttag taagaccta 42060 aaactgaatc tcagtagttt gagcttatga tatacagat gcagctctaa catttaatt 42120 ggaagggaaa tgtcaaaag atacctgcac tcttgttgt tgcacactg tttacatag 42180 ctaagatttg gaagcaacct aagtgtccat caccacaa atagataag gaatgtgat 42240 atatatacac aatggagtac tattcagcca taaaaaagaa tgagatcctg tcatttacaa 42300 spacatgggt ggaactgag atcattatgt tagtgat aatccaggca spacaagaca 42360 aacttcacat gttctcactt atttgtgggc tctaaaaatc aaatcacttg aactcagaga 42420 gattagaagg atggttacca gaggctggga agggtggtga ggggttgggg gcagtgaaga 42480 tggttaacag gtacaaaaaa ctagaaagaa tgaataagac ccactaggtt ttttgttgtt 42540 ttgttgttgt tgttgttttg agacagagtc tcactctgtc acccaggctg gagtgcagtg 42600 gcatgatctc ggctcactgc aacctccacc tcctgggttc aagcgatcct cctgcctcag 42660 cctcccaaat agctgggatt atgggcacgc gccaccacac ctggctaatg tttgtatttt 42720 tagtagggac cgggtttcac caggttgaac aggctggtct caaactcctg acctcaagtg 42780 atccactcgc cttggcctcc caaatgctca gattacaggc gtgagccacc gcacctggcc 42840 actgtttgat agcataatag ggcgactata gtcaataata acttaatggt atatttttaa 42900 ataacttaaa gagtataatt ggattgttgt aactgaaagg atcaatgctt gagggcacag 42960 ctaccccatt ccccatgacg tgtttagttc acattacatg cctatgtcaa agcatctcat 43020 gtaccccata aatatataca ctgagtatat accacaaata ttttaaataa tttttaaaat 43080 aaaaaaaataa attgtaaggg aaagaaaatt atgaatttag aaatgtaaaa ggtctcaggt 43140 aaagaa tgagaggatc atgcagaacc tcccatcatt gctgggactg gaacagaagc 43200 cctaccttt cccaacaccc tatccacctg tccctcacct ctcagctttt gtgagactct 43260 gtctgtgcta tgaaactgaa gatctaattc agtgctgttt gcattgtctt gcctcctgga 43320 ccagaggttg cagttgttga gaaaagggat ggttggttat gccttgatcc cccccagagc 43380 atttggggca taggacacgg gaactggcca gcctggttca ctcttctcga ttagctggac 43440 agcggcatgt catgtgggta ataggaaggg gtggggactt ccccgggata ttctgctcct 43500 gatcagaagc gccagtgatg tgggggagc cccagcacca gagcatgctg ggagggcgtg 43560 cagggtgggg caggtgcccg tttggcctct gctgtctatc tggggatgc atccaaaggc 43620 aactgttcct tatctgctct tgttgggagc aaagggc caatttgttc aatgatccgt 43680 atacagccag tccctctggc cagagttcaa gacagtattg cctcactcta tatagagatt 43740 gtatcttggt tagctcttca ttcatagcaa gaccaatgtt tctgtaaatt aatcctggta 43800 ttgtttaaaa gcaactaaaa atgatgaaat tgtaaaactt tgaaactccc tgaatataac 43860 gacaagcaaa ctaacattgt tttatggtc gatgctcctg gccagaagag agaattag 43920 cagggataaa aggcataggc cacatgcatt ttccacccca gtgctgagaa cacgatgggc 43980 gaaaaaggga ggtggccaca gcccatccat cacacagtct ctgcccatct acttgctttt 44040 tccttttttt ttttttttt ttttgtgaca gagtctcgct ttgtcaccca gactggaggg 44100 cagtggtgca atctcagctc attgcaactt ctacctccca ggttcaagcg attctcctgc 44160 ctcagcctcc cgagtagctg ggattacagg cacctgccac caagcccagc taatttgttt 44220 gtatttttag tagagacggg gtttcaccat gttggccagg ctggtttga actcctgacc 44280 ttaagtgatc agcccacctc agcctcccaa agtgctggga ttacaggtgc gagcaccac 44340 gcctggcccc agctacctgt tttctttctt tttttttttt ttttttcttt ttttgagaca 44400 aagtcttgct cttgtccccc aggctggagt gcaattgcat gatctcagct cactgcaacc 44460 tccacctcct gggttcaagc gattctcttg cctcagtctc ctgagtagct gggattacag 44520 gcgcctacca ccacgcccgg ctaatttttg tatttttagt agagacgggg tttcaccctg 44580 ttggccaggc tggtttcgaa ctcctgacct taagtgatct gcccgcctca gcctcccaaa 44640 gtgctgggat tacaggtgtg agccaccatg cccggcccca gctacttgct ttctattggg 44700 atgaacctca tggttaatac agttagttag tgactgcaac ttttgaactt tttgttcata 44760 gtgaaaaata ttttaagtaa tgcttacccc attatgtttc ttgtcatttg aaaaaaaatc 44820 tcccttcaga cagaatgcag aataaaatac tacagaaaat ctgtacagag tcccagcctg 44880 acttatgcta gtaggttaca gagaaagaaa gtcttctaaa ccctatgaaa ggttaacagt 44940 tctcttattt ttccctgtgt gctatttgat gatttccctg tgaactttga tgatttattg 45000 ccagaattcc aaacataata tgtgaatttc acaaaaatgg atgaaatgta tctatttttc 45060 attggtagaa gaagccaaaa catcccttcc tcaccgcact aaaagctgtt gtttacatga 45120 agcaaacctc aaatgtgaac atatttttac gcaaatgcat ttaatgggtg aatatttgct 45180 ttgggacggt attctttact ctatctggag agtctggcgt tccgtaatca ccatgtgatg 45240 acggctgccc tgacagtggc tggtagcagc acataccccc gagccctcc gtggtgtgcg 45300 ccgtgggcac catgtgacca ttttcagaa ggaagacagt tctggaagct aaggtcacc 45360 tagtcagcct cgttgggtga ttgatgactc agctgggttc agggaggtgg acccgaggca 45420 gagcctectag aaggcagcgg tgggcagggc ggttcaggca ggtggcacct gggcaaggt 45480 gcagacgtgg aatcctgaaa gcaatctca gcgctgctgc gttccagga ggtagaagaa 45540 cagtgacaag tgcacagtcg ggtagggaca atgtggaag ggctgggaac agtgtgttca 45600 ggagactggg cttcaatctg gaggtctcag gaagtggttt aggatgtttc agcgagagca 45660 tgatacagac taacccagga agaaccgctg ctttgtcact atacccta tggaatgcc 45720 gttcgctttg ctagttgaaa tagcctacca ttgtctggga ctcacccagt tagattgtt 45780 tggactccac aaagtattct tgaccataca atcatgtcg aggaccccct acatgagctg 45840 ccttcatggc tacagggaga gcacaccaaa gtggatgtca cacccagcac acatgccacc 45900 ggcttggccc tgcgccccgc agcctgagcc acactggctg cctgttcctg gaatgtgcca 45960 acatgtttca gtcctggagc ctttgcactt ggtgttctct tcgctggaac attctccccc 46020 aagacattta cacagcttgc cccctcattc cctgaggtta tctcctgccc cctaatcagt 46080 gaggccttcc ctggcctcac cccggacact ccacacgtgc attcatttcg ttgttcacca 46140 tctgtgtccc agttacaagg gaggctccct gagagcaggg atctgatttt tgttagttgt 46200 tgttgttgct gttttgaggt ggagtcttgc tttgtcgccc aggctggtgt gcagtggtgc 46260 gacctcagct caccgcaacc tccgcctccc atgttcaagc ggttctcctg cctcaacctc 46320 ctgagtagct gggattacag gtgcctgcca ccatgcccag ctaatttttg tatttttagt 46380 agagacagag tttcatcatg ttggtcaagc tgccctccaa ctcctgacct cgtgatctgc 46440 ccacctgggc ctcccaaagt gctgggatta caggcatgag ccactgcacc cgaccctgtt 46500 ttttgtttgg ttttggtttt ggtttggttt tggttttttt ttgagacacg gtctcactct 46560 gtcgccccgg ctagagtgtg gtggcaccat ctcggctcac tgcaacctcc acctcccagg 46620 ttcaagtgat tctcctgcct cagcctcctg agtagctgggg attacaggca catgccacca 46680 cacccagcta attttgtat ttttagtaga gatggggttt tgccatgttg gccagtctgg 46740 tctcaaactc ctgacctcaa gtgatccgcc cgcctcggcc tcccaaagtg ctgggattac 46800 aggtgtgagc cactgtgccc ggcccaggga tctgtttttg tctccgctgt gtccccagca 46860 cctcaaacat attgtacgga gctgcgacag ctgcgcagtc agtgatgact gagagattcc 46920 tggccccgtg ggctatggct ccttcaacag tttgttgttt aaaggttctt cactttctca 46980 gcgtgctgat caagacaa gcctggagga gaggctcagt ggtgctcctg tgtagatgat 47040 gaattcaggt gtatcttgga tggtaaatga cgttgcattt aaaaccaagc aagtggccag 47100 gcgcagtggc tcacacctgt gatcaaagca ctttagaagg ccgaggcggg cggatcacct 47160 gaagtcagga gtttgagacc agcctggcca gcatggtaaa aacccgtctc tactaataat 47220 aaaaaaaac tagctgggcg tggtggcggg cacctgtaat cccaccact cagaggctg 47280 aggcaggaga attgcttgaa cccgggaggt ggaggttgca gtgagctgag atcgcaccac 47340 tgtactccag cctgggcgac agagcaga cttactca aaaaaaaa aaattaaaaa 47400 ttaaattta aaattaaaac aacagccgg acgcagtggc tcactcctgt atcgcagca 47460 ctttgcgagg ctgaggcgag cggaatacga gctcaggaga tcgagaccac cctggctaac 47520 acagtgaaac ccgtctctac taaaaaaaaa aaatacaa aaattagcca ggcgtggtgg 47580 caggcgcctg tagtcccagc tactcaggag actgaggcag gagaatggtg tgaacccgggg 47640 aggcggagct tgcagtgagc cgagattgtg cccctgcact ccagcctggg siacagactg 47700 agactctgtc tcaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaac 47760 aaacaagtga acgttgttat acgtcagtct taccaattgt tcctctttcc tcccagtagc 47820 ttggagctcg gcggcacaac cagcaccac tggtcgcgat ggtggacacg gaagcccac 47880 tctgccccct ctccccactc gaggccggcg atcgagag cccgttatct gaagagttcc 47940 tgcaagaaat gggaaacatc caagagattt cgcaatccat cggcgggagat agttctggaa 48000 gctttggctt tacgggaatac fottttag gaagctgtcc tggctcagat ggctcggtca 48060 tcacgggtaa gtgtgccgtt tcctagaaag ttttatttag aaatgtttct tcctccaaga 48120 aaactgttct ctcttttttt ttttttttt tttgagacgg agtctcgctc tgtcgcccag 48180 gctggagtgc aatggctcga tctcggctca ctgcaggctc cacctcctgg gttcacacca 48240 ttctcctgcc tcagcctccc gagtagctgg gactacaggt gcccgccacc acgcccagct 48300 aatttttgta tttttaatag agacgggggtt tcactgtgtt agccaggatg gtctccatct 48360 cctgacctca tgatctgccc gcctcggcct cctaaagtgc tgggattata ggcgtgagcc 48420 accgcgcccg gccgaaaact gttctcttta gctggaaaag aagtcacact tttttgcaaa 48480 gaaagcttca gacgtggtaa agcatgacct ccagtgcccc tgggccctgg aaggcgcgtg 48540 tcacggctca cggtgccccc tcttgtgaaa gccatgcaca catcaaacag tgcttgagat 48600 tcagtcacgg ggaacagcta aagtacacag accctaaccc cagcaagccc gcggggggca 48660 gctagacatt tttaagagga gacgtgtgca agggtctgca tagaggtact gttggtaaga 48720 gggaaggatg ggaaacaagc tgtacatgcg tcaaagggaa acagataaat tgggatgcat 48780 ttatacagtg gtatatactt catagcaatt taaaagaaca gactaggcta ggcgcggtgg 48840 ctcacgccta taatcccagc actttggaag gccgaggcaa gtggatcact tgaggtcagg 48900 agcttgagac cagcctgacc aacatggtga ggccccatct atacaaaaaa aatttaaaat 48960 taaaaaaaat tagccaggca tggtggtgca tgcatgtggt cctagctact caggatgctg 49020 agggaggagg accacttgag cccaggagct cgaggctgcc atgagctatg actgccactg 49080 cactccagcc tgggtgacag tgagaccctg tctttaaaaa aaaatttttt taagcaacat 49140 tgaatgaaaa taaacaagct taatgaatat ttttatgatc caattaatgt aaaatctttt 49200 attttttatt ttttgagaca gagttttgct cttgttgccc aggctggagt gcagtggtat 49260 gatctcagcc cactacaacg tccatcttcc gagctcaagc agttctcctg cctcagcctc 49320 cctagtagct aggattacag gcaccccgtca ccatgccggg ctaatttttg tatttttagt 49380 agagatgggg tttcaccgtg ttggccaggc tggtctcaaa ctcctgacgt caggtggtcc 49440 gcctgcctca gcctcccaaa gtgcagggat cacaggcatg agccactgca cccggcccaa 49500 ttaaaatctt taaactaaa caatctagta catcactggt ggaaagac atacacctat 49560 tgcaaagggc atctcagctt taggactca gtcacctcct gagcaagatg gagggagaac 49620 tgggggagggg tcccatgggg actgtaattc tctctaggtt gtatattttt aaaagacttc 49680 agcagtgtga taaacctggg tggtgtgtac atgggtatta cagtcatgtt gcttaatgac 49740 agggacaggt tgtgagaaat gcatccttag gtgatttcat cattgtgtga aagtcataga 49800 gtacacttaa acccagatgg tagagcctgc tgcacaccga ggctctgcgg tgcagcctgt 49860 tgctccaagg cacgcacctg tacagcgtgt tactgtactg aacggcgtag gcccctgtga 49920 cacaatggta agtatttgtg cgtctaaaca taccaaaaca tatagtagaa aaggtttacag 49980 caaaaataca gtattatcat cttatgggac catgatacca cagttgaact tatggtctat 50040 tgttgaccaa atgtcactg tgcagtgtgt gactatacag aaataagctc agagaaatta 50100 agtaacttgg ctgggcgcag tggctcacgc ctgtaatccc aacactttgg gaggctgagg 50160 caggcggatc acccgaggtc aggagttca gaccagtctg gccacatgg caaacccca 50220 tcttactaa agaatacaaa acattagctg ggagtggtgg caggtgcctg taatcccagc 50280 tactctactc aggaggctga ggcagggaga attgcttga cccaggaggc agaggttgca 50340 gtgagcagag atcatgccac tgtactctag ctgggcgac agggtgagac tccatctcaa 50400 aaaaaagttg gggcgtggtg gctcatgcct gtaatcccag cactttggga ggctgaggcg 50460 ggcggatcac ttgaggtcag gagttaaaga ccagcctggt siacatggtg aaccccatc 50520 tctactgaaa atacaaaaat tagccaagca tggtggtaca cacctgtaat gcctgggcaa 50580 cagagcaaga ttccgctca aaaaaaaaa aaaaaaaagt aagtaacctg caccaggttca 50640 tacagccaga agacacaga gccggggcctg gaccccgcct ctcagcttgc tctagaggggc 50700 tattctctgc atgctggcat gatcgcgcct tgtaaaaggt ggcagtgttc tcagcttagt 50760 caatcaggaa ttgcaagagg caagtgagcc cctgaggact ctggggggcc tttgtgaccg 50820 agcagctttg ggagtgaccc tgacagacct ttacaggtgg tgcaagtttt gactcccttt 50880 ctcctggcgc gttaagcaga ggataagcgc tgtggaagga gtgaaggtgt agggagatca 50940 tggcccccag agcagtgggg aaggggacag ggaggctgga ggagagcaag gaaaaggctc 51000 cgtgtcaggt ggcgccttga gtggcctggg taggttgtct tgcagtgaac ccgggttaat 51060 ggccttgaca atgaccgcat tgtttcctga gcactgcagg ctgcccacac acctcacacc 51120 tcggcttgcc taagcccaga gcagccttgt gaggtcgttg ttatgtttat ttaaggaagg 51180 aggaaaggag gcaggtccca ggacatcctg acgtgctgga gatcaccagc ccagaaccca 51240 gctcttaacc ccacaatgtg ggacctttct tcacccatca cagacacacc ccatgctggt 51300 tcaccgtttt cctataatga ctatttgtgc tatttattag aaaaatcttt tccttatgga 51360 tttgaaaaga tttatcttgc ttttgtttt cttttttgcc tttctttttt aaggcaggca 51420 ggctcccgca gccccacccc cagggtgaaa aatatagttc attgtctagt aaaagagttc 51480 agagatacac ttttttcttt gggtaagata tactctagag cttgttctga aatatggaat 51540 ttgtgtgagc tgcgggagtg ggtgggtgtg tggctctagc tctggaaagt tctttcctgg 51600 cagtggccag gagggctgcc cagccccctc ctgcctcctc tggcagctta aacacaggac 51660 cccttattct gtgctctctc ctgacccctg gtcctcatgc aggagggaac cctgctcttc 51720 tagggtcctt ttctaaaagt agtgtctttt aggtcattgt caagaactat aatctaaaat 51780 gtatttttaa ctcatctgga aattctgaca gaggtaaggc ttgagaattt cctgcatact 51840 agccttgtgg tctatataat ccattaaaag ccacatttaa cccaattcca cagactgaac 51900 tgtgcttcc atctaaataa attaaaagca ggccgggcac ggtggtcacg tgtgtaatcc 51960 cagcactttg ggaggtcgag gcgggtggat cacctgaggt caggagttcg agaccaacct 52020 ggccaacatg gtggaacctc atctctacta aaaataaaaa aaattagctg ggcgtggagg 52080 cgtgcacctc ttaagcttaa ggacatattt cttatgatcc aattaatgta aaatatttta 52140 ttttttattt atttttgag acagagtttc actcttgctg cccaggctgg agtgcagtgg 52200 tgcgatcttg gcctgtaatc cggctactc aggaggctga ggcaggacag tcgcttgaat 52260 ccaggaggcg gaggttgcag tgagccaaga tcacaccact gcactccagc ctgggcaaca 52320 gagtgagact ctgtctttaa ataaataaat aaataaatag cgagggttca gggcaggaga 52380 aaaagggttc caaatttgtt ctgaaccaat tccaaggaac tttatggcac aaagaaaaaa 52440 aaggggaact tacaaaaagt gaccacactg aagcgtcctg gtcacccatc cctggttttg 52500 accaccagcc tttaaagtgg caagcgggtg ataacccatt tcttatttcc ccctcagcat 52560 ttcctcactg ttattcatac atgtggtcat ttgtactcat ctcacaattg ttaaaacctc 52620 tttcctccct tccaggtttt actgaactgt tactgcgaag tctgagagat gaggtcattt 52680 aagattattt cttatttgta aattagatcg ttcatatttg tacctaatct gatctttttgg 52740 gtaatattcc tagttatgta gactggtctc tcagaagagc cggatattaa atgcagtact 52800 ttaaacttta cacccaggag accggatggg tgaggctggt tcactcggcc aaagtaccat 52860 tttatctctg ctttttcttc ccggctttat tgccataatt gacatacaat aaactgcatg 52920 tatttaaagt gtacaatctg ttgggtgtac acacacacgc atctgtgaaa ccatcatcac 52980 actcaaaata gtgatgtaga aattttgctc cttagttcga ctaaatctgg gttcttgtgt 53040 catgaccagg aaaaattagg cacgtggaca cgttgaaggg tgaggagagc agtattgggc 53100 gaaaaggaaa aaagaaaaaa actctcagca aagctagagg ggatcctgcc aatgagttcc 53160 cagctcacag actgattagc aggccaccac acatgagctg gaggccaggc tcctcccgct 53220 gcgcaaggtg agaacttccc gtggctccac cccattctcc caatgcccag gtgggtcccc 53280 gtcccttgcg ggcctgtcca gacaagggaa ccctgggcag gttccctcat ctacacaaaa 53340 gcacctgagg taaacacttg tggggcaggt tgcagattct ctggggacgc cccccttctc 53400 tgcctcctgc atctatcagt agtgcctctg tctgtcaccc ctaaagttta cttgtgctgt 53460 ttctaattcc tctttcccca gccccgtgcc tccctgcctc cctcccccag taaaccatga 53520 atccactttc tatcattcta ggttgcttta tatttcctag aattttatat aaatggaatc 53580 atacagcacg tactctttct aggctggctt ctttcactct gcagaatggc tgtgagactc 53640 atctgcattg cagcaagcat caatagttca ttcttcatcc atcatgtgga catagcacag 53700 tttgctgatt cacgcacctg ttgatgagca tttaggttgt ttctagctta tggctattac 53760 aaataaagct gctatgaaca ttcacgtaca agtctctgta caaccctctg ctttcatttc 53820 ttttgaataa atacctagga gtatgacggc tggaacagat ggcaggtgtt tgtgtaactt 53880 tttaagaaac tgccaaaatc ttttccagca tttcagaaaa atcttagaaa atgctatact 53940 atgttatatt cccactggca gtatatgggg gagttccagt tcctccatac cctcatcaac 54000 atgaggcatg atcagtcttt ttaattttaa ccatgtcagt aggtgtgtga tggtctctca 54060 ctgtggtgat ttttatttgc acttccctgg tgattttgag catcttttcg tatgcttatt 54120 tgccatatat cttctttggt gatatttctg ttcaaagcct ttgctcattt tttaattgag 54180 ttgctttct actattcact attgaacact attatatat tttgaataca aatactttat 54240 cagacatgtg atctacaaat atttcccca gtgtgtggtt tgtctttctt ttctttctac 54300 tgatagtatc ttaaaaaaaa aaaagaaaaa agattgtttt gtttgttttg ttttgttttt 54360 gagatagggt ctcaatctat tgcccaggct agagtgcagt ggtgcgatca tggcttactg 54420 cagccttgac ctcttgggct caggaaaccc tccgacctca gcctcccaag tagctgggac 54480 cacaggtgtg taccaccatg cttggctaat tttttttttt tagatacaga gactcgttat 54540 gttgccaggg gtggtcttga actcctggac tcaagcgacc ctcccacttc ggcctcccaa 54600 agtgctggga ttacaggtgt gagccatcat gcccgaccag ttcttaattt tgatgaagtc 54660 caatttatca atgtcctttt tttatggata cttcatttat ttatttattt gagagagggt 54720 ctcaccctga gcccaggctg gagttcagtg gcatgatctc agctcactgc agcctcaacc 54780 tcccaggccc aggtaatcct cctacttcag cctcccaagt agctgagact acaggtacct 54840 gccaccatgc ccgggtaagt ttttgtatt tatttgtaga gacggggttt cgccatgttg 54900 cccaggttgg tctcaaactc ctgggctcaa gtgatctgcc catctcagcc tcccaaagtg 54960 ttgggattac aggcgtgagc caccatgccc agccatatat atatatatat atatatatat 55020 atatatatat tttttttttt ttttttttt tttttttttg agacagagtc tcactctgtt 55080 gcccaggctg gagtgcagtg gtgcaatctt agctcactgc aacctcttc tctgaggttc 55140 aagtaattct catgcctcag cctctttagt agctgggatt acaggcatgt gctaccaggc 55200 ccggctaatt accagcctta tatttttgaa ctctgtttaa aacatttagg tgcataaaca 55260 ttcaggcttg ttatattctg ttgatgaact gaacctttta ttattatgaa attgctgttg 55320 taatccgtgg taaaattatt tgttctgaac actactttgt ctgttattga tgtagccact 55380 gcagctttct tttgattggt gttaacatgg tatatctttt cccattcttt ttcttttaac 55440 tggtttgtgt ctttatacta tggtttgatt taaatctatt atctcacaat ttgttctctt 55500 tggtacatct ttgttttgtt cccttttcct ctttttatgc cttctgttga attaattgag 55560 tcttttttgt tttgtttcat ttaattttgt tttttgagac ggagtctctc tctgtctcca 55620 ggctggagtg caatggcgct atctcggctc actgcaacct ctgcctcctg ggttcaagca 55680 attctcctgc ctcatcctcc tgagtagcta ggatcagagg catgcaccac cacgcccggc 55740 taatttgtgt gtgtgtgtgt gtgtgtattt ttactagaga cgggtttcac tatgttggtc 55800 aggctggtct caaactcgtg accttgtgat ctgcctgcct tggcctccca aaatgctggg 55860 attataggcg tgagccaccg cacccagcct aattgagtca tttttaagat tccactttat 55920 ctcctttgtt ggcttattat ttataacacc ttctggtgtt attttagtag ttgctttagg 55980 gtttatagtg tatctctcta atgtctccca gtctaccttc cagtggtatc attctatctt 56040 acagatatta taagaacttt atgacagtat actttcattt ttcccttcat gcatttgtgg 56100 taatgtttca cataatttta tttatttacc tacattataa atattacaat atgttattgt 56160 tttacataga cagccggtta tctttttaag atagtagtaa gaaaaatttt ttacatttac 56220 ccacataatt accttttcta gtgctatata cctttgtata aatccagatt tccatctgct 56280 atcattttcc ttctgcctga aagacttcct gtgatattat ctataatatg gctctactgg 56340 taacgaatta ctagcttttg tatgtctgaa aaagtcttca tataaccttc attctagaaa 56400 gtatgtgatt caaagggccg ggcacagtgg ttcacgcctg taatccgagc actttgggag 56460 gccgaggcgg gtggatcacc tgaggtcagg agttcaagac cagcctgacc aataaggtga 56520 aaccctgtct ttactaaaaa tacaaaaatt agctgggcat ggtggctcat gcctatagtc 56580 cctgctactt gggaggctga gacaggagaa ttgcttgaac ccaggaggca gaggttgcag 56640 tgagccaaga tcacgccact gcacaccagc ctgggtgaca gagcaagact ccatccccct 56700 gcaaaaaaaa agaaaaagaa aaagaaaaaa gtatgtgatt ctacattggc aatttttttt 56760 tttttttttt ttttgagaca gagtctcgct ctatcaccca ggctggaggg cggtggtgcc 56820 atcttggctc actgcacgct ccgcctccca ggttcacacc attctcctgc cccagcctcc 56880 caagtagctg agattacagg cacccaccac cacacccggc taattttttt gtatttttta 56940 gtagagatgg ggtttcacca tgttagccag gatggtctca atctcctgac ctcatgatcc 57000 gcccacccg gcctcccaaa gtgctgggat tacaggcatg agccaccgag cctggccact 57060 ttttttcttt aaatgctttt aagatgttcc tactatcttc ttgtttttaa ttaattaatt 57120 tattattatt attattatta tattattat tatttttttt tttttttt ttttttagaga 57180 cagggtcttg cgctgatgcc gaggctggag tgtgctagtg ccatcgtagc tcactgcagt 57240 ctcaaacacc tggtctcaag caatcgtcct gcctcagcct cctgaggaac taggactaga 57300 ggtatatact accatgccca gccaatttta aaaattttt gtagaggtgg agactcgcta 57360 tgttgaccag gctcctctcg aactcctggc ctcaagcaat cctcctacct ctgcctcccg 57420 aagtgttggg attacaggga ttacaagtgt gagccactgt gccagtcccc actgtcttct 57480 ggcttgcatc gtttctaaaa gaaacttggt gtcatcctta tttttgtttc tctacatgtt 57540 atatgtcctc tttatctggt tgctttaact ttatttatta atttagttt aatttttaat 57600 tgacaaataa taattgtatt tttatggggc acaatgtgat gttttggtct atgtttacat 57660 tgtggaatgt gtaaatcaag ctagtgaaca tatccaccac ctcacacact taccattttt 57720 tgtgtgtggt gagaacatgt aaaggctgct ccttgaggcc aggcccaatc ccagcacttt 57780 gggaggccga ggcgagtgga tcacttgagg tcaggagttc aagactagcc tggccaacat 57840 ggtgaaaccc cgtccctact aaaaacacaa aaatcagcca ggcgcggtgg tacacgccta 57900 tagtcctagc tacttgggag gctgaggcag gagaatcact tgaacccaag aggcagaggc 57960 tgcagtgagc caagatcatg ctactgcact ccagcctggg caacagagca agactccatc 58020 tcaaaaaaaa aaaaaaaaag tctattcctt gagcaattttt gaaatacaca atacatcatt 58080 gttaattatg gtcaccatag tgggtagtag atcactaaat cttattcttc ctgtctaact 58140 aaaacttttt tccttttgac caacatctcc ccattccctc cctcaacctc agcccctgat 58200 aaccaccatt ccactctcta ctgctatgag tttgaccttt ttagatttca catatgagat 58260 cacatggtat ttgtctttct gtgcctggct tcttttactt agcataatac cttccagatt 58320 tacccatgtt gttgcaaatg gaatttcctt cttttttaag gctgaatagt attcgtgtgt 58380 gtgtgtgtgt gcgtgtgtgt gtgtgtgtgt atcacatttt ctttatctct tcgttcatta 58440 atgatcattt aggatgattc cacatcaggc tactgtgtat agtgctgcag taaacatgga 58500 agtgtagaca tctcttcagc atactgcttc caatctcttt ggatataaac ccagaagtgg 58560 gattgctgga tcatatgtag tgctattttt gtttttttga ggaacctcca tacttatttt 58620 gcataatgct attctaattc acaatactac caacagtgga catgggttct tttttctcta 58680 catgcttgcc aaccacttgt tatcttttat ctttttatat atctggctgc ttctaaattt 58740 ttttctttct taccaattct gaaccatttg atggtttctt cctttatgct ccttgtgctt 58800 gaggttcatt gagcatctgg gatcagtgca cttattgttt tcatcaaatt cagaagatta 58860 ggccattatt tcttcaaact tttttgtcgt tctctgtcta cctttgagag ctccaattat 58920 acatacatta ggccacttga agttgtcatt acagttcact aatgctaagt tcttttttta 58980 agtcttgttt ctgtgtttca ttttggacac tttctattgc tacatcttca aatttactaa 59040 ttttttcttc tgcaatatct aatctgctcc taatcctatc cagtgtattt tccatattag 59100 atattgtagt tttcataact agaagcatga tttggttctg ttttcaccca tgtatctata 59160 taacatgtcc agtctttcac tcagcttctt aaacatttag aatatggtca gaataacttt 59220 ttttgctgtt ttgttttaga gacagggtct cactttgtta ctcaggctgg agcgcagtgg 59280 catgatcaca gctcactgca gccccaacct cctcgtctca aggaatcctc ccacctcagc 59340 ctcctatgta gctgggacca caggtacaca ccaccacacc tggctaattt ttaaattttt 59400 tgaagagacg ggtctcactt tgttgcccag actggtctca aactcctggg ttcaaacaat 59460 cctccagcct tggcctccca acgtgttggg attacaggca tgagccactg tacccagccc 59520 agaataactt tttaaaaatg tcttgaggcc gaggttggga aataatctga ggtcgggagt 59580 tcgagaccag cctgaccaac atggagaaac cccgtctcta caaaaaatac aaaattagcc 59640 aggcacagtg gcacatgcct gtaatcccag ctacttggga ggctgaggca ggagaattgc 59700 ttgaacccgg gaggcagagg ttgtggtgag ccgagatcac accattggac tccagcctgg 59760 gcaacaagag cgaaactcca tctcaaaaaa aaaaaaaaa aaaactctta gccacaattt 59820 ctatcatctg tgtcacttct gagtcccttt ctattcagtt atttttctcc ttgtcatggg 59880 tcatattttt ctgattcttc atgtgtcctg taattttcttt ttcttttttt ttttggagat 59940 ggagtcttac tctctcaccc aggctgtagt gcgatggcac aatcttggct cactgcaacc 60000 tccacctcct gggttcaagt gattctcctg cctcagcctc ccaggtagct gggattacag 60060 gtgctcacca ccatgcccag ataattttt gtatttttag cagagacggg gtttcaccat 60120 gatggccaag ctggttttga actcttgacc tcaagtgatc cgcccacctc ggcctcccaa 60180 agtgctagga ttacaggcat gagccaccgt gcctggccag ttgttctcat tggatgtcat 60240 atgttgggaa cttattggg tgatggatat ttttgatttc ctataaatat tcttgaactt 60300 tgttctggga tgcaattaag ttacttggaa aatctttgat cctttcaggt cctgtttctc 60360 agcttcatta gatgggacta tcacagtgtt tgttttagag ataactttgc cccactgctg 60420 aggcaaaacc actttgagct tcacctgatg ccccatgact tcagtgatct tccactgtgg 60480 gaggcgagag caggactata tccagctcca tgtgggcccc aggcagcgtt cactatcatc 60540 atttcaggtt gctactgaag tatccctttt tcaggctctc agctggcaga gcaaatacat 60600 atatgtatac atactaacct atgtctatac aggaatctat cggtatttct gtctgtggcc 60660 atctgtagct gtatgaagcc aaacatgagt gtgtgctgat gtctccagcc ctcatctgtt 60720 accagatgga tcgttctagc ctcctccact tgcctacctg tcaattcacc attccttgag 60780 ttcatggttc attttcagta tacctgcaca gtggtatcag aactgttaac ccacaccctg 60840 tgggaaaaaa actccatcag ctagagcaca gtgtttacag ccagatcctt ttgcctttag 60900 tcttacagat tccaatcatt ccaaattat cggtgcagcg cctttccgca cctgcaccca 60960 ctttttcccc tgagattgtt tcctacattc gtagcacagt tagattgttt tgttacattc 61020 tgcatttcac cctgggatcc tccaacctcc taagttattt ttgttttatt tgcacacatt 61080 aggttcaatc tgaactataa agttctgtgg gttttcacaa atgcgtagtg tcatgtatcc 61140 accactacat tttccttctc tctctttctt gctttctcgc cttcttgtct tgctctgtca 61200 cccaggctgg agtgcagtgg cacaatctcg gctcactaca acctccgtct cctgggttca 61260 agccattctg ctgcctcagc ttcccgagta gctgggacta caggcacgca ccaccacccc 61320 tggctaactt tttgtatttt tacaaaatac aaaagacgat gtttcactat gtgggccagg 61380 ctggtctcga actcctgacc ttgtgatcca cctacctcgg cctcccaaag tgttgggatt 61440 acaggcgtga gccaccacac ccggtctctc tccttccttt cctttcctct cctttccttt 61500 tctttctttc tctttccctc tcctctcttc tcctctcctc tcctttgatg gaggtctcac 61560 tgtgacaccc aggctggagt acagtggcag cataatctca gctcactgta gcctcagcct 61620 cccagggctc aggtgatcct cccacctcag cctcccaagt agctgggatt acaggtgcac 61680 accgctgagc ccagcaaatt tttgtatttt ttgtaaagat agggtttcac catgttgccc 61740 aggctggtct caaactcctg agctcaagtt atctgccagc ctcggcctcc caaagtgctg 61800 ggatgacagg catgagctac cgtgcccaga ccactgttag attttcatat gaatagtttc 61860 accacatcaa aaaaccccat gcttcaccta ttcaaccctg cctctcccac ccccagccag 61920 ctcagaaatg gttcttttta ccattgctat aattttgcct tttccagaac gccatgaatt 61980 tgaaatcata tagtatgtag ccttttcaga ctgacttctt tcatagcaat atgcatttaa 62040 gagtcatcca tgtctttcca tggcttgata tctcatttct ttttacactg aatgagttcc 62100 cactgtctgt ttgtaccaca gtttgtatat ctattcacct atctaagggc atcttggttg 62160 cttccaattt ttggcaatta ataaagctgg ccatgcacag tggctcacac ctgtaatccc 62220 agcattttgg gaggccaagg cgggcagatc acttgaggtc aggagtttga gaccagcctg 62280 gccaacatgg tgaaacgctg tctctactaa aaatacaaaa attagccggg cgtggtaatg 62340 ggcacctgta atcccagcta cttggaaggc tgaggcagga gaatcacttg aacctggagg 62400 cagaggttgc agtgagctga gatcgtgcca ctccactcca gcctgggtga cagagtgaga 62460 ctctgtccca aaaagaaaaa gaataaactg ctgtatacat gtgtaggttt tgtgtggaca 62520 gaagttttca aatcagttgg acaaatacct aagagtgtga ttccatcata cagtaaaact 62580 gctttgcttt gtcagaaact gccagaatgt cctccaaggg ggctgtctca tgttgcattc 62640 ccaccagcaa tgaatggggg ttcctgttgc tccacatcct caccagattt gatgatgtca 62700 gttttgtgga ttttagtcat cctagtaggt gtgtggtgac accacattgt tgttctcatt 62760 ctcagtgccc cgatgacata tcatgctgag cattgtttca tatgcttact tgccatctgt 62820 atatcgtcct tgctgaagtg actgttcaga tgttcagatc ttttgcccat tttctttctt 62880 tttttttttt tttttccttt tgatacggag tcttgctctg tcgccaggct ggagtgcagt 62940 ggcacaatct cagctcacta caacctttgc ctcccgggtc caagcgattc ccctgcctca 63000 gcctcccaag tagctgggac tacaggcacg caccaccatg gcaagctaac tttttctttt 63060 ttttttcttt tctttttttt ttgagatgaa gtctcgctct gtcacccagg ctggagtgca 63120 ttggtgcgat cttggctcac tgcaagctcc gcctcctggg ttcacgccat tctcctgcct 63180 cagcctcccg agtagctgggg actacaggcg ccccaccac gccccggctaa tttttttgtg 63240 tttttagtag agacggagtt tcaccgtgtt agccaggatg gtcttgatgt cctgacctcg 63300 tgatccgctt gctccggcct cccaaagtgc tgggattaca ggcgtgagcc accacgccta 63360 gcccccattt ttcaattgag ttgtttgttt taagacctct ttgtatatta ccacatgtgt 63420 attgaaaata tttctccca gtctgtggct tgtctttaat tttcttagca atgtcttttg 63480 cagagcagaa ggtttcatta gctttcatag attccaactt atattttctc tttcatggat 63540 tgtgcatttg gtgttgccca cacagatttt tatactgtat tctggtgcca tttactgagt 63600 taacaattgc ggagaactg gaaaagga agcaaacaaa acgagttctg cgtggcactg 63660 tcagtgcggg ggcatgggga gtcctgcagg gtgaggtatg ggcggtatgg caaggcgcgg 63720 gcccatagat gtgcaggtct ggagatgtgt gcagcggaga tgtgcgggcc cgagatgtgc 63780 gggtccgatg tgtgggtccg gagatgtgcg cgtacccaga ggtgcagatc ggaaatgtgg 63840 gggtccggag gaaatgtgcg gatcaggaga agtgccagtc ccgagatgtg cggatcggag 63900 atgtggaggg ctaggagatg cgtgggtccg gagatgcgca gatcaggaga tgggcgaatc 63960 ggagatgcgc gggtccggaa atgtgcagag cggagatgtg tggatcagga gatgttgggg 64020 ggtcaggaga tgcgggggtc cagagatgtg ggggtccgga gatgtgcggg tctggagatg 64080 tgcagagcag agcaaagatg agctgatcgg agatgcccag gtccggggat ccacgggtcc 64140 ggagacgcgc gggtccggag atgcgtgggt ccagagatgt gcgggtccaa agatgtgcaa 64200 atctgaagat gtgtggatgg gagatgtgca ggtccggaga tgcgcggggc ggagatgtgt 64260 ggatcggaga tgctcagatc gaagatgtgg gaatgaggag atgtgcgggg cgggatgtgt 64320 ggatgggaga cgcgcgggcc cggagatatg cggggcggag atgtgcgggt ccagggatgt 64380 gtgatctgag gtgtgtgggt ccggagctcg gggtcagctc agcagcagtg agagcgagca 64440 tgctggcttt gggagcacag cacaatggca gctgtaggag tgcaagaggg tgtgacccag 64500 aggcagggcc cggccccgca tgggtgttct gaggtttatg cctcagcact agaagcctcg 64560 tatgcgaaat cacatcctca tagacccggt tcagacacag gatagtgatg cctggactat 64620 tcatccgtct ctcctctttt tccccagaca cgctttcacc agcttcgagc ccctcctcgg 64680 tgacttatcc tgtggtcccc ggcagcgtgg acgagtctcc cagtggagca ttgaacatcg 64740 aatgtagaat ctgcggggac aaggcctcag gctatcatta cggagtccac gcgtgtgaag 64800 gctgcaaggt agaggggagc tggaacaggg cctggtggcc gccaccatca actacttatg 64860 gtcactttta tagcaaatgg cagtcattac tgagagattg cagaaagtcc cggataagaa 64920 actgacttca ggccaggcgc ggtatctcat gcctataatt ccagcacttt gggagaccga 64980 gatgggtgga tcacctgaga tcaggagttc gataccagcc tggccaacat gatgaaaccc 65040 tgtctctact aaaaatacca aaaaaaatta gccaggcgtg gtggtgggcg cctgtaagcc 65100 cagctactcg agaggcaaag acaggagaat tgcttgaacc caggagccag aggttgcagt 65160 gagccaagat tgcgccactg cactccagcc tgggcaacaa gagtgagact ccatcttaaa 65220 aaaaaagaaa gaaaaaaaga aaaagaaaaa gaaactgacc tcagtgatag attagcctct 65280 ctttatagca cagaacccct gagagcgtaa gccctgttgt gaactgcgta tttgaggaat 65340 ctagcttgta cgccccttat gagaatctaa tacttgatgt tccaaggtgg aacactttca 65400 tcctgaaact atccctcccc acccccatct gtggaaaaat tgtcttccat gaaaccggtc 65460 cctggtggca aaaaggttgg ggattgctgc tttagagagt ctaggacaaa tggttcctct 65520 gtgctttgta ataacttaga gaagtgcatt ctttaaaaga aaataagtca cattggaccg 65580 ggtgcagtgg ctcacgccta taatctcagc actttgggag gccgaggcgg ctggatcacc 65640 tgaggtcagg agttcaagac cagcctggcc aacatggtga aaccctgtct ctactaaaaa 65700 tacaaaaatt agccaggtgt ggtggtgggt gcctgtaatc ccagctactt gggaggctga 65760 agcaggagaa ttgcttgaac tcaggaggcg gaggttgcag tgagctgaga tcgagccatt 65820 tcactccagc ctaggcgaca agagtaaaac ttcatctcaa aaaaaaaaa aagagagaaa 65880 agaaaataag ccacattaag aacatcactt cattcgaata caagacagag agctgttacc 65940 gttgatctct ggagcctccc tgaaggccag gtggggcagg tgttctcatg ctcctgccag 66000 ggaaattggc catcagagac acagagtatc ttgcttaggg tcccacagcc cccagcagca 66060 gggactggaa ccagagactg gctgctcctg ctccccagca gttccttcct gcacatcagg 66120 ggcttctcca cctgattcaa gcgacaggaa ccccctgtgc atcttcatcc tcctgctggc 66180 tcagcctgcc ctaaacagat gtgacctggg ccaggagtgc atgaaggcag gccctgttgt 66240 cctgcatgct gccagctgga ctggtggccc ttccgtgttt gtcagcgtgg tgatgaggag 66300 agctcctgta gcagcgtccc tttagggttg cacagacgtg ctcaagtctg gcgccttatg 66360 tacgtgatat gtgggagatc atcatctgaa tgtttggttt gaatcagaaa tcccttctca 66420 cggtgcacgc tgcaggtgtt cactaacttg gaaaatgcca ccgcctttct ggcacaatgt 66480 accatcttgg aacaccagca ttctgccctg agccaggcct ggcctcagag gcctgggcca 66540 cagggagaac ctcacagcca ggacactgtg gcactctgct gtctagaagc ctgtctcccc 66600 acccttccca ttctaacccc atgcgttcct cagcctcccc actgtgcaag cctaggtaag 66660 gacattatga agacgtcagc ctgcctctca cattcccctg cacactgctg tccctctccc 66720 gcgggccaag cagacccact gtggcaaaaa tatagaagaa tgacttaaaa gcaaagagaa 66780 aaaagaaccc aaagcaaaaa tgaactcctt cgcatgtttt ctaaccatat acctttgaaa 66840 aagctcctta taaagtggcc ttttccttag ggccatgatt aattattcat ttagtttgt 66900 tttttatgga ctatttagta acattgtttc ttgctgggta gagtttaaga tgcttttaca 66960 aagcaagaaa attgtttaca aacagctggc ttccttttat tataattttt gtctttgagg 67020 gagttaatat actcttacaa aaattcttag aaagtcttta gtcacaaata tggaaatgtc 67080 acaatgctgg ggatagttac attcatatac attgtaacaa ggctgagtaa ctctttggaa 67140 aactataatt gtgttttcc aagtcagatg agggcatttt gaaatgactt cgaatgctgc 67200 ctcattttat tgttttcac attaaatgta acgacattta aagttctgta tttgtcctaa 67260 tcattccaga cttcttagaa gaactatttc tttctttttt tttttttttt tttttttttt 67320 tttgagatgg agtctcactc tgtcgcgcag gctggagtgc agtggcacaa tctcagctca 67380 ctgcaacctc cgcctcctgg gttcaagtga ttgtcctacc tcagcctcct gagtagctgg 67440 gactacagac ttacatcacc atgcccggct aatttttgta tttttagtag agacagggtt 67500 gcaccatgtt ggctaggctg gtctcgaact cctgacctca ggtgatccac ccgcctcagc 67560 ctcctaaagt gctgggatta caggcatgat caccatgcct ggcctggaat aacttttctc 67620 taaattttgt tcatttaaaa agaaacaata aatgagcaac aaaaaaggtg agtaaagcaa 67680 gtgcgctggt ttctcagtgg cccaggtctt taaatccact gtgtattacc ctcacagggc 67740 ttctttcggc gaacgattcg actcaagctg gtgtatgaca agtgcgaccg cagctgcaag 67800 atccagaaaa agaacagaaa caaatgccag tattgtcgat ttcacaagtg cctttctgtc 67860 gggatgtcac acaacggtag gtaaggtggc cctgcacatt ttcccagttc gttcctcagt 67920 tccccttcct tgctccaagg gaacagatca agctatggat gatgtgctt caacatttca 67980 cacccaagtc attttgtaat cagagtggcc taagaaata aaagtcgccc aggcgcggtg 68040 gttcacgcct gtaatcccag cactttggga ggtgaggtg ggtggatcac ctcaggtcag 68100 gagtttgaga ccagcctggc caatgtg aaaccccgtc tctactaaga atgcaaaat 68160 tagctgggtg tggtgcaca tgctgtagt cccagctact cgggaggctg aggcagaaga 68220 atcgcttgaa cccgggaggc ggaggttgca gtgagctgag attgcgccac tgcactccag 68280 cctgggcgac agagggagat tccgtctcac aaaaaaaaaaaaaaaaaaaaaaaagaaaga 68340 aagaaaataa aagtccca gtgcggtgg ttcacacctg taatcccagc actttggagg 68400 ccgaggcgggg tggatcactt gaggtcagga gtttgagacc agcctggcga acatggcaaa 68460 accccgtctc tataaaaat aaaaatta gctgggcatg gtagtgcaca cctgtaatcc 68520 cagctacttg ggaggatgag acaggaat agcttgacc cgggaggcgg aggttgcagt 68580 gagctgagat cgcaccactg cactccagcc tgggcgacag agtgcgactc cgtctcaaaa 68640 aaaaagaaaa aaaaagaaaa agtctcaaat agctgagatt cagtggtgca ttggactcgc 68700 tgttagaaac ttcagtggta agactttgat acagaatcga aaaaccaagt ggaaggcacc 68760 aaaatgacag aatgttcacc tcgtccatag gaagggtgta ccacctcaaa catctcacca 68820 cgttatgaat ttccttctag ccaatcattt aatagtttca gaacatgcta attgtgatgt 68880 gaatgtaagt cgttcataag agttgcatgt ctaccttctg gaaaaagaag cagttattat 68940 ataaactcat cccgaagccc cgttcacctc cttcactcaa aggttgatga tgcacctgat 69000 agtggtgtgc accctactaa tgagacgaac gatggtgtca ccttcagcct gcacctgtta 69060 acgatggtgt caccttcagc ctgcacctgt ttaaacatct acagtgtatg gagtttgagt 69120 ttttcatctc tccatagtgg aaagccgaat agtaatgaag gatgggtctg aactgcctgt 69180 gaattttcat tcctggttta aagtcctggg ggagcccctc gtccagccct gtccgcgcag 69240 tcatgacctc actgctcatg cctgtgtttc cccctccaaa ccctagcgat tcgttttgga 69300 cgaatgccaa gatctgagaa agcaaaactg aaagcagaaa ttcttacctg tgaacatgac 69360 atagaagatt ctgaaactgc agatctcaaa tctctggcca agagaatcta cgaggcctac 69420 ttgaagaact tcaacatgaa caaggtcaaa gccgggtca tcctctcagg aaaggccagt 69480 aacaatccag taggtgttg cggctgttct gggttctctt ggcaacatgg aaccagtgtc 69540 gtagaggacg attaaggaca catgtgttga atgttgagaa aattatatttt atcccacagt 69600 taagcaaagg acagcgaaga tggaaacagt tcattctgag actctgagct gtagcttaac 69660 aacaactcct ttcttcttgc ttggagccac ctcaaagctc ttagcaacta agttattata 69720 ctggctatgt aattaataca cttaaaaaaa accttaatag cttaccaagt actaagatga 69780 tttctttagga gcattttttc ttaaatagag ataggttctt gctctgttgc ccaggctgga 69840 atgcagtggt gcaatcatag ttcactgcag ccttgaactc ctgggctcaa gcaatcctcc 69900 tgcctcagcc tcccaaggag ctgggactac aggtgtgcac caccacacct ggctatgttt 69960 gatgttgttg ttgttttgtt ttgtttttgt ttttggtag agatgagatg tttcccaggc 70020 tggtctcaaa ctcctggcct caagtgatct tcccacctcg gcctcccaaa gcactggcat 70080 tacaggtgtg agtcatggca cccagcatta actggattta aaaaaaaaa aactgaccag 70140 gcaagatggg tcatgcctgt aatcctggca ctctggggag gccaaggtgg gcagattgct 70200 tgagtccagg agtttgatac cagcctggcc aacatggaga aaccccaact ctactaaaga 70260 tacaaaaatt agctgagcag ggtggcacac acctgtaatt ccagctactt gggtggctta 70320 ggcatgagaa ttgcttcaac ccgggaggca gaggttacag caagctgaga tcatgccact 70380 gcactccagc ctgggtgaca gatcgagacc ctatctcaaa aaaaaatag aataataaaa 70440 taaatcccta ctttgaggtg tattagtctg ctataaagaa atccctgaga cctggtaatt 70500 tataaagaaa agaggtttaa ttggctcgtg gcccacaagg ctgtacagga agcttctgct 70560 tctggggagg cctcagggaa tttgactcat agcagaaggt gaagtgggag taggcgtctt 70620 gcatggcagg agcaaaaaca agagacacac acttttcacc catcagatct tgtgagaacg 70680 ctatcactag agtagcacca agaggatggt gctaaaccat tcatgaagga tcaccccat 70740 gatccagtcc ctcccgccag gcctcaccctc caccactggg gatcagtt caccatgaga 70800 tttgggtggg gacagagc spaccatt cataggcta gaaaaggaaa spaccattt 70860 cccactcaa atgtgctctt ggtcctttct cctaaaacta ctccctccct ctcagacaaa 70920 catgcctaca ttctttcc gccttcagtg aaagacagt gatacttgg ggcttagaaa 70980 gggccacttg taagccaggc gtggtggctc acgcctgtca tcccact tggggaggcc 71040 aagacaggcg gatcacgagg tcaggagatc aagaccacatcc tggctacat ggtgaacac 71100 catctccact aaaaatacaa aaaattagcc gggcgtggtg gcggggcgcct gtagtctcag 71160 ctacttggga agctgaggca ggagaatggc gtgaacccag gaggcagagc ttgcagtgag 71220 ccgagatcgt gccactgcac ttccagcctg ggcgacaaag ccagctgtgt ctgggcgcgg 71280 tggctcatgt ctgtaatccc agcactttgg gaggctgagg tgggtggatc acttgaggtc 71340 agggatttga gaccaccctg gccaacatgg tgaacccca tcttattaa aaatacaaaa 71400 aattagctgg gcatggtagc ggttgcctgt aatcccagct acttgggagg ctgaggcagg 71460 agaattgctt gaacctggga gctggaggtt gcagtgagct gagatcgcac cactgcactc 71520 cagcttgggc aacagagtga gactctgtct caaaaaaaaa aagaaaggaa aagaaaggac 71580 cacttgttat agaaagcctg tcttttaagg tagctctgga ccttttcaga ggcagccaaa 71640 ttgcccctca tggttcgtcc cccacatccc cgcctgcctg gcctaagtcc tccttccccc 71700 tccccaacag ttaaataagt ctttgtctcc attacaaaac aaatctcaga gctaccttca 71760 aagaagagcc agccctcagt tggtgaatga agatactttg acattttcct atgagcatgg 71820 tgaaacaggt ttaatttgta ttaaatagct tgaagcaatc cttattggga attacaaggt 71880 ggaattttag tcacaggaaa ataaagcatt tcacaagcta cttactttca tgaacaaacc 71940 aaacctcttc tttactgagt cctttaattc ttcagtgaat tctccaatta aataggccga 72000 gacattttag aagtttccag cagacaccca cactaggcag ctccagaggc ttgtcccaat 72060 tagaactttc ctggattacg agagtgaaag aaaaggtaac ttttagcttc gagtctctat 72120 cctggatatg attagtacag cccaaaattg ggatggctaa aacttttgtt tgccagctta 72180 tatttctcc ttggatttca gaattgaaag caggctggggc acagtggctc acactgtaat 72240 cccagcactt tgggaggctg aggcgggagg atcacttgag gcaatccaag agtttgagac 72300 caggcaacac aaggagacct cgtctctaca aaaaatgatt ttttaaaaaa ctagctgggc 72360 atggtggcat gtgcctgtgg tcccaggtac ttgggaagct gagatgggag gatggcttga 72420 gcccaggagt tcaaaaccaa cctgggcaac atggcaagac cacatctcta caaaaaataa 72480 aaacattatc caggcatggt ggcacatgcc tatagtcccc gcgacttggg aggttgagga 72540 ggatgccttg aggcaggag ttcaaggctg cagcgagcca cgatcgcgcc actgcactcc 72600 agcctaggcg acaaagcgag actctctaaaa aaaaattcga agcagagtta agttgtcttt 72660 cttcctaaca acctgcccc accatggggt gcgaatggga ctcctggagt cctcctgcac 72720 ctccccttgg agaccaccaa gctctaggaa ccccatcacc ctcagctgag ggtcacatgc 72780 agcaactagc aggcggaat ctgtttgcat tttggcctta aagaataaa taataggcca 72840 ggcgcggtgg ctcatgcctg taatcccagc actttggg gctgaggcag gtggatcacc 72900 tgaggtcagg agttggagac cagcctgacc atatggtga aaccccgtct ctactaaaaa 72960 tacaaaaatt agctaggcat ggtcgtgggc acctgtaatc ccaactacc aggaggctga 73020 ggcaggagaa ttgcttgaac ctggaggca gaggttgcag tgagccgaga cacaccact 73080 gcactccagc ctgggtgaca gagcgagact ccatctcaa aaaaaaaaa aaagagggcc 73140 aggcgtggtt gctcatgctt atgcctgtaa tcccagcact gtgggaggca gaggaggggcg 73200 gattacctga gctcaggagt tcgagaccag cctgggcaac atggtaaac cccatctcta 73260 ctaaaataca aaaaattagc cgggcatggc agtgtgcgcc tgtagtccca tctattcgggg 73320 aggctgaggc aggagaatgg cgtgaacctg ggaggtggag gttgcaggga gccgagatca 73380 caccggtgca ctccagcctg ggtgacagag tgagactcca tctcaaaaa aaaaaaaaag 73440 aaaaaatga tagatgaata gtttaggatt ggggttcaca atttggttt ctgtagaaaa 73500 agagaaccgg gcactcttcc gagagtcaga tgccctcttc cacccacacc cacaaagcca 73560 gagcaccgca ggtaccagtt ttcaaggcaa cctccaacca tcatgtgact ctttgtgttt 73620 gatcacactg tttgctccaa gccagggttg cgtcccaccc catgtccttg tctgcgcacg 73680 ggacgctgga ggcacggccc cctctcccct gcctagcctg ctgacgggct ttccagagct 73740 ggctccttca ggtgcaggat accctctctg cttagtctgg gaaaaggccc cgttggcagg 73800 atgcccacca ccaggccaca ctgcctgaat ctattggcag agctctggtt ttgtggccaa 73860 ggtgggtagt ggaagaccat agcctgtgtc ccttacacat ctcagaaagc aaccccatct 73920 gtgggcaaga aatctgttag ggagaccaag cagcggcctg gaaacacctt gatctctgcc 73980 cagtggccca catgcggtcg ccgtttcatc agtttccagc ctgggtgacc tcacagcccc 74040 agccacgccc cacagagcct caggaaggca cactgacctc agggccggcg gctgacttca 74100 tttctgtttg gggatgagag gcggcacagt aaactgtcca ggccagtaaa ctaatggatt 74160 catacgaacc gtaatgaacg tgggctgtgt gctggggaag gcaggctcgc ctcctccctg 74220 caggggctgc tggggtgaaa gcaaccctga aatgttcaaa gccttgatgg ggaagcacgg 74280 gggatggata gattttaatt tcaaagcagc cctctggttt gctataagcg ggggactgaa 74340 tttctctttg cagtggccaa tgcctttctt ctgtcaagat cagctcgtgg ccttcagatc 74400 agatgacgca aagccccatg gctgagctgg aacaggctag aatgctgggg gggggcctga 74460 aaccggtggg ggagttgtgg gaggcctaga atcagccagg aggcttgggt cggggttgga 74520 accggccagg gtgcacggag gaggctgtgg gggcaggggg aggccgctgc atggagccgc 74580 atagatgcca ttgcttgagg aaaggtgggc tttagctgag ggaaggagtg aggggtggat 74640 ggagaatgtc tgtgtccatc tggacactgg gactgtttga gcccctgaga tttcagaacc 74700 gtgggccaga aaatggtcag ggcccttggt gatggggaag ggcgcctctg gggaactcac 74760 tgccccttga tttgagggta acagggatgg aagcagagtc agggggctga gggaggcaat 74820 aaaaatgggt gctttcaac agtgtctaa aacatagat gttgacctgt caggggttga 74880 gatgtcgtc agagacttt ggaggaagca acagaaatg agactgagggg gcttgggcag 74940 agtcagtgcc ttctgtgtga tgcacgctca tgcacaatg cacgcacata cccacactca 75000 cacatccgtg cacacacggg tacacaca tacacgtgca cccacatgca tgctcacaca 75060 catgcaccca cagtcacaca tccatgcatg catgtgtaca caacacacc cacacataca 75120 catgcaccca cacgtgtaca cagatgcacc tccacccca tacatgcaca tggacacaca 75180 catgcaccca cacgcacaca agcatccatg ctcacatggg tacacactca cacatccatg 75240 catgcacgtg taaacacaca cacccccaca catacacgtg cacccacaca tgcacacaga 75300 cgcacctcca cccccacaca cgcacacaca cacatgcacc cccacatgga tacacccaca 75360 ctcacacatg cacacacc tgtgtgtaca cacacacatg catgctcaca cacacacacc 75420 caggcacaca caaatccaca ttcacccata cagtcacaca catgcataca cacacataca 75480 aacacatgca ttcacacaga tgcatacaca cacacactta caaactacac atgtgcttat 75540 acatgctcac atgcatgtat atgcacacac ataccctcac cttatgcaca catgtaccca 75600 cacacgtacc cacacatata caagcatgca cacatatatata tatacaca tgctcacacg catacccaca ctcacatgtg tgcacatatg ctcacacaca cgtgcacaca catgctcaca 75720 cacacactta ctgttgctca ggcttagctg ctttgggctt aagaagcaaa ctgcaccttc 75780 caaaaaatga gtgtggtgtt cagttaaaca accaataat tctttagcac tgaatatgtg 75840 gactttagaa attcaacta taggtgata ataacgttgt cctgctactt tttaatctaa 75900 cieacatatc agaactgaca ctcagttcaa atgagaag taggaatttgg gcgtgccgtg 75960 ttattttc aaagattctc ctattgctcc aaattgttgg ggattactt aaagtctttg 76020 atagcttca gttatggaag atttaccct ctgagaatag aactgaattt tagacaacc 76080 atgagtccat tgtagctaga ctggcatgca agttgggat aaacagagta aaacgtcttg 76140 tttaaaaaaa taagaaggc cggcttgggc aacatagtga gacctccctct atgaaagtt 76200 agctgggcat ggtggtgtgc gctgtggtt ccagccgctc aggaggccga ggcaggagga 76260 tggaggtcaa gactgcagtg gactgtggtt gcgccactgt actccagcct gggtgacaca 76320 gcaagacccc gtctcaaaa aaaaaaacag aaaaaagttg agcaaggaga 76380 ctaatttgtg acatgcagct gaacatggtt tttaagacca gttttgaag aggaattcca 76440 acattattct taacattca gaagcctggg cataagggtg acctccagggg tgccgtgtta 76500 taacaggact gctcctttca acagctatga ccttatacca tgtcttgggg tgttgcctgc 76560 cgtgtgacag tccaatatta tacctactac ttaagttttc tttagatta aaatgtgct 76620 tcatatttta tgccattctct acaaatgtat agtaaaacat aaccaagaga gcttattaaa 76680 taatttcatc caaagcagtt ctaccagtgc ttcacattta ttttttt atttattt 76740 ttttgagact gagtctcact ctcttgccca ggctggagtg cagtggcgca atctcagctc 76800 actgcaacct ccccctcctg gttcaagcg attctcctgc ctcagcctcc taagtagctg 76860 ggattacagg tgccagccac cacacccgac taatttttgt atttttagta gatacggggct 76920 tttgccatgt tggccggct ggtctcgaaa tctgacctc aggtcatcca cctaccttgg 76980 cctcccaaag tgctggcatt gcggggcatga gctactgcgc ctggtccaca tttaatttt 77040 tgcaaaaga tgacagctgc taacagagat gattctcat gagtgatatc attgagcttc 77100 gtaggccaca tgagtgtgtg ccgggaccag tgtggcagca agcggggcgt tctgctctcg 77160 gcatggagtg attggggaaa atctaggcag cttcctgcct cacgctgttt aaaaccttta 77220 taatgtgctt tattcaattt atttgaatg actgcctgtc gtgtcagata tattcatagt 77280 caagcttgag tataaaaggc atattccaaa gttaaatata agctgctgca tagattttt 77340 tgtaaaatga tctcaccaag aatgtttatc cataaagtttt agcgaatttg caagtgtgtt 77400 ttcacagc atttctttt agctttaata aacattggtt tctcatggt accactcatt 77460 ttgaattcag tggtctccag ttctccctgc taaatgaggc ccacttcta aaaccaaagt 77520 gataatttta taaaaatgaa atgagatatt tgttaccaca gaagtcctca ttacgagag 77580 tacatcccca tagaactagt ccacggtgag cctcaggggc atgcaagctg tttaacgatg 77640 cccccagcct agaaaggccc aggcttgggt gttcatgctc cgctgttgcc ttcttgaaat 77700 tcataatcat ctttgaacaa ggggtcccgc agtgtgtggt ggctcacgcc tgtaatccca 77760 acactctggg aggctgaagc gggtggatca cctgaggtcg ggagtttgag accagcctga 77820 ccaacatggt gaaaccccat ctctactaaaa aatacagaaa ttaaccaggc gtggttggtg 77880 ggtgcctgta atcccagcta ctcaggaggc tgaggcagga gaatcactca aacctgggag 77940 gtggaggttg cagtgagtcg agatcacgcc actgcactcc agcctgggca acagagcgag 78000 actccgtctc aaaaaagaaa aaccaagggg tcccacattt gcatttttgc tctgggtcct 78060 gtaaattacg tagccaggcc tgcatttgtc ctgggagatg ctctaccaaa aaaataaa 78120 taacaccaag cattctgtaa tcaaacactg taggaacccc tgcttatcct agcctcattc 78180 tcattctgga agactgcaca tttatcatgt taaagactca gctagggagg cccaacttca 78240 ttcaactcag tgtttcttat ttttttaaaa cagaactcat tttttaaaaa aattatggc 78300 tgggcgtggt ggctcacgcc tgtaatccca gcactttggg aggctgaggt gggcggatca 78360 cgaggtcagg agatcgagac catcctggct aacacggtga aaccccgtct ctactaaaaa 78420 tacaaaaaaa aatgagctgg gcatggtggc gggcgcctgt agtcccagct actggggagg 78480 ctgaggcagg agaatggcat gaacccggga ggcggagctt gctgtgagcc aagatcacgc 78540 cactgcactc cagcctgggc aacagagcga gactccatct caaaaaaaaa aaaaaattat 78600 ttaacacctt tatttctgct gaatgtactt tagaaagatt gagtgatttg aataaagtga 78660 cggtggccta agagtctatt ttctggaatt gagggaatac tgccatcgat ccttgaaaaa 78720 tatttattta gttcctccta gaggccgggc acagtggctc acgcatgtaa tcctggcctg 78780 cactttggaa ggctgaggtg gacagattgc ctgagctcag gagttcaaga ccagcctggg 78840 taacaaggtg aaacccgtct ctactaaaat acaaaaaatt agctgggcgt ggtgatgtgt 78900 gcttgtaatc ccagctactc gggaggctga ggcaggagaa ttgcttgaac tcaggaggcg 78960 gaggcagagg ttgcaatgag ctgggattgc accactgcac tccagcctgg gcaacagagc 79020 aagactctgt ctcaaaaaaa aaaaaaaatt atctagcccc tcctagaat gttaattcct 79080 taaatctgag cttcagcttt ctgtgaagca gattatctc cieacttaa caacaatgg 79140 tcagaactgt tttaggtc ttggagag atcattttca gtctttatta atcggacttg 79200 agatttatta gaaacttggc tctgaatatt gtattcagaa tgtttcact catttgtgag 79260 taatttttta atatcccct ttcctcagat gcagaatcag ggctttttgt ccagcattat 79320 gttgcaagtc ctggttctgt tgaacattc cataccatct gtgtgatggt tatcggcacc 79380 tccaccggtg ccctgaagac agttttgtgc tgtgagtcca gaaacaggaa acacttcagg 79440 ctgtgtgtca gaagcattgt cagtggttgt gttttgcca ctggcagggg gcattcttta 79500 aatcctggga tgcttctgcg ctttgggctc cactgttcca gcagtgatta gaaataacgc 79560 tgtaggccgg gcgcggtggc tcaccctgt atcccagca ctttgggagg ctgaggtggg 79620 cagattacct gaggtcagga gtgcgacacc agcctgacca acatgtgta accccgctc 79680 tactaaaaat acaaaattag ctgggcgtgg tggcgcatgc ctgtaatccc agctactcag 79740 aaggctgagg cgggagaatc gcttgaacct gggaggccga ggttgcagtg agccgagatt 79800 gtgccattgc actccagcct gggcaacaag agcaaaactc tgtctcaaaa aaaaaagaaa 79860 taacacctta gcccactgca ttattgacct gtgtctgcat gagctgtgga ccacattata 79920 atcagagaga tctctcagat gttgtcactt tcctgctcta cccgcagatg taaatttcag 79980 ccaacagcag tgtttgtgct cattttcccc ggctctccca cacatgtaat cccttctgag 80040 catgttggct tcaaataata tggccagcca cctcttccac cacgagatct tcaggaaatg 80100 gcaggccact gggtttacat gcagatggca tgggagcaca caaggcacgg ctgtggggag 80160 ttggcacttg ctccagaata tggagcaccg agtgaaggtt tcagtttcct gcactgagag 80220 aaacaagggc attccgaggc ttttccactt tatccctaaa gagtttcaca acgcttgttt 80280 gccgatttct acatagatgc cacctttctg agttgtatgt atttacatgc caaatgtatt 80340 cattgagcag cgttaataa tggtgttcac ccctaaagtg catatactgg taaaattaag 80400 aatgatcgta attaagcctc ttgcaatagt cattagttca gagaatattt aagaatatta 80460 aaggtgcttt gctaatgtcc tcgttagttt tgttttgaca aaatcagtac ttcagtttct 80520 tgtttctttt ttttttgaga cggagtctta ctctcgctct gtcgcccaga ctggagactg 80580 gagtgcagtg gcacgatctt ggctcactgc aacgtccacc tcccaggttc aagcgattct 80640 cctgcctcag cctcccgagt agctgggggtt acaggcacac actatgcctg gctaattttt 80700 tttttttttt tgagacggag tctcgctctg tcacccaggc tggagtgcag tggcgcaatg 80760 tcggctcact gcaagctctg cctcctgggt tcacgccatt ctcctgcctc agcctcccga 80820 gtagctggga ctacaggcgc ccgccaccac acccagctaa tttttttgta tttttagtag 80880 agacggggtt tcaccatgct ggccaggctg gtctcgaact cttgacctca ggtaaaccac 80940 ccacctcagc ctcccaaagt tctgggatta caggcgtgag ccaccatgcc cagcccagta 81000 cttcagtttc ttagcgatga aatccaccca atgtcaggcg atgactatta ttattttact 81060 gatttatact gtttgttctc tattaatgtc ttattttccc caaccgattt tgaagttgag 81120 taaggactat gttccgcggg tatcttgagt cctctgaggc actgagcttg gtgatttgga 81180 cgcaggagct gctcattagt gagctgatag ctgggagcat agcgcatccc acatcacctg 81240 acttaccttg gtgtcctcct ttgtagcctt ttgtcataca tgatatggag acactgtgta 81300 tggctgagaa gacgctggtg gccaagctgg tggccaatgg catccagaac aaggaggcgg 81360 aggtccgcat ctttcactgc tgccagtgca cgtcagtgga gaccgtcacg gagctcacgg 81420 aattcgccaa ggccatccca ggcttcgcaa acttggacct gaacgatcaa gtgacattgc 81480 taaaatacgg agtttatgag gccatattcg ccatgctgtc ttctgtgatg aacaaagacg 81540 ggatgctggt agcgtatgga aatgggttta taactcgtga attcctaaaa agcctaagga 81600 aaccgttctg tgatatcatg gaacccaagt ttgattttgc catgaagttc aatgcactgg 81660 aactggatga cagtgatatc tccctttttg tggctgctat catttgctgt ggaggtgagt 81720 ggttgattta atctgctggt atcatgtcac tgacaggctc ctgtcttgaa aaatttgaca atgggaaatc cagtaccagc ctgagctgtt ccagtggagg ggacactcac atggtgggaa gacgtctgac ccccagtcac tgctgagaat tcagtggga ttaacaat attgtataat attachment attachment tatctaaa tacatattta attachment aatgtatgac attttaatca fathertagc caggtgtggg ggtgcacacc tttagtccca gctacttact cagtagactg aggcaaaagg atctcttgag cccaggagtt caggttgcaa tgagttatga atgcaccact gcactctagc ctgggcaaca gaacaagacc tatttcttta aaaaaaaatt fatherttttg cacaaatata father aaaagaggtc ggacatgggc ctgtaatccc agccctttgg gaggctgagg tgggtggatc acttgagccc aggaggttga gaccagcctg 82260 ggcaacatgg caagaccccg tctctacaaa aaaaaaaata gaaaaaatta gtcaagtatg gtggcatgta cctgtagtcc cagctacttg agaggctgag gtgggaggat cacttaagcc 82380 82440. caggagacaa aggttgcagt gagccaaggt cacgccacca cactccagcc tgggcgacga agaatgaccc tgtctcaaaa aaaaaaaaa aaaaaattat acacacacac acacacacac 82500 atttcgttta tattatatct aatattataa acagatataa tttatatt atgatattcc 82560 tgtatatt atataatgat gttgtattca tattatagac aatattgtat gaagtgctat 82620 acagatgtca gtatagttgc tgtcacagtt ggttatgttg atgaaaagta tatttcctaa 82680 tgcaaaatat aattcagtc agcagccaag tggcagtgac tgcaaggttt gctttgcccg 82740 aggaagcaga tcccagggaa ggccgatctg gtcctctctg tggaagctgg ctctgcagcc 82800 tccacattt tggctcggtg tcacgttcct ttaaatagcc ccatctcagg tctaggaagg 82860 tcatccacct actgcaaact cggctgacct tacccagggt tggtggagac agatggggtc 82920 tcccacactg cctgcagcca tactgcgcct gggggattga ctcactgtca gcatggagct 82980 gactcagccc taccagccgt gccgttact gtgtggctgg gcacaagtca gatgaaggaa 83040 gtccttgcgc tctggcataa agtgtacaaa gacaaagcag ttatgcataa tttgtccttt 83100 agtatggtca ggatgtagca ttgtgggtaa aatgcagttg cagaactatt tatatgtagc 83160 atgatcacag ttttataag gaaattataa tcctatatca atcctatgta tatagaaaaa 83220 tgtccagtga gatatatgtt aaacctatta tggtggtt aaaattatga ggggggatt 83280 ctatttttca aaagattcct cctttttttttttttgaga cagagtctcc gtctgtcacc 83340 ctggctggag tgcagtggca cgatctcagg tcactgcac tccgcctcc tggttcag 83400 tgattcgcct gcctcagcct cctgagtagc tgagattaca ggaacatgcc agcacacctg 83460 gctaattttt gtatttttag taagatggg gtttcaccat attggccagg ctggtctcaa 83520 actcctgacc ccgggtgacc cacccaccctc ggcctcccca agtgctggga ttacaggcat 83580 gagccactgc acccggcaat aattccctc tttagagact taatagttat agccccagcc 83640 actctggagg ccgaggcagg aggattgctt gagcctagga gttccagtcc agcctaagca 83700 acagagcaag acccatcac taaaacaata CAAAaaacaag aattttagaa aaaaactt 83760 aaattaca tttacacca aaaacaatga agatgtttaa atcctcatca ctagcaaccc 83820 tgttaagaat catagtaatg actgggtctg taagggagca ccgcctgctg aacatggctc 83880 agggcagtat tttctggacc aagaatcagg tctcatgctt tgagactgtc ccaggatgtc 83940 tagtgccagc tacccaggc aggtcatctg gtgtgaatgt tgactcttcc tgcaccaagt 84000 ctcagacctg ccccaccctc ctccccactc tgggtctcct gatcttggct cactgcaatc 84060 tccgtctccc aggttcaagc gattctccca cctcagcctc ccgagtatct gggattacag 84120 gcgtgagcca ccgtgcctgg cctacaaaac ctagttctaa cacaatcact ccttaaatat 84180 ggtggaacac ttgaagcttg atatctagtt tggattcaaa agcttcattt cccatattat 84240 gcaaaactgg tggttgtgat ctccagaatg tactgttcct cctactagct ctaatttttc 84300 tccctgacag gtggtcatca ggtaaatcac aagtgaaaag gccgcaccat aaggtgtact 84360 tagggcacta ttgccgccta gtagtatgaa tatttaggaa agagtactgg tcctgtctgt 84420 ccctacttca cctattgact ttggaaaaac ctatgtctat cttccagtca agttgacaat 84480 atctaaaggc agctcagttt ttttctaaga aaggccacat aaaataggca tgtttggttc 84540 ctgaaactga taagcagttc ttgggtgatt atcacactca aacctctctc tcttctttcg 84600 agactagatc gtcctggcct tctaaacgta ggacacattg aaaaaatgca ggagggtatt 84660 gtacatgtgc tcagactcca cctgcagagc aaccacccgg acgatatctt tctcttccca 84720 aaacttcttc aaaaaatggc agacctccgg cagctggtga cggagcatgc gcagctggtg 84780 cagatcatca agaagacgga gtcggatgct gcgctgcacc cgctactgca ggagatctac 84840 agggacatgt actgagttcc ttcagatcag ccacaccttt tccaggagtt ctgaagctga 84900 cagcactaca aaggagacgg gggagcagca cgattttgca caaatatcca ccactttaac 84960 cttagagctt ggacagtctg agctgtaggt aaccggcata ttattccata tctttgtttt 85020 aaccagtact tctaagagca tagaactcaa atgctggggg taggtggcta atctcaggac 85080 tgggaagatt acggcgaatt atgctcaatg gtctgattt aactcacccg atgttaatca 85140 atgcacattg ctttagatca cattcgtgat ttaccattta attaactggt aacctcaaaa 85200 ttcgtggcct gtcttcccat tcaccccgct tttgactatt gtgctccttt ataattctga 85260. aaactaatca gcacttttta acaatgttta taatcctata agtctagatg tatccaaagg tgaagtatgt aaaaagcagc aaaatattta tttcaaagac ttcacttctg tttcctgaat ctaaagaag acaacatgct gctttttaat cataggatgg agaattttaa agaactgttt gggccaggca cagtcgctca tacttgtaat cccagcactt tgggaggccg aggcgggtgg atcacaaggt cagcagatcg agaccatcct ggccaacatg gtgaaaccct gtctctacta 85620. aaaatacaaa aattagccgg gtgtggtggc acatgcctgt aatcccagct actcgggaag ctgaggcagg agaattgctt gaaccaggga gttggaggtt gcagtgagct aagactgcac 85740. cactgcactc cagcctggtg acagaacgag actctgtctt aaaaacaaac aaacaaaaaaa aaaatctgtt agataagcta tcaaaatgca gctgttgttt tgtttttggc tcactgtttt cgtggttgta actaatgt ggaaaggccc atttccaggt ttgcgtagaa gagcccagaa aacagagtct caagaccccc gctctggact gtcataagct agcacccgtg gtaagcggga 85920 cgagacaagc tcccgaagcc cgccagcttc ctgctccact cagctccgtc cagtcaacct 85980 gaacccaccc agtccagctg tctgtgggaa tggtggtgtt cttagggaca gactgacacc 86040 ttacttgtca gtgttcctcc gggccccatt tggcagctcc cgtatctttt gttatgttgc 86100 ttttaaagat atgatgtttt attgttttaa ctcttggtga cagtagatgc tctctggagc 86160 gcagacgagg cacatgtgtc ttcatagcct gggctgggtg ggagccagtc accctgcgga 86220 tcgagagagg gggtagagtc ttcttcaaat ggcagtttta cttcaaatgg cagatttcac 86280 aagagttggt tattttttac aatggtttag gttgttaagt ctcctttgta tgtaaggtag 86340 ttttttcaac atctaaaatt tttgttttag ccttcaaaac caacttacca acctcagtcc 86400 agctgggaag gcagcgttga ttatggtagt ttgtcaagaa tatatggacc tggaaacact 86460 ttctctctct gtccacctgg tagataaatt gtcctgttga gaatttttag atctggactg 86520 gaactgccag gaccaccgcc tccagggagt cgctgggcac ctggaggtat cgtcgatgcc 86580 tctcccccat cttagaaaa tttggctctt ctgaggtcat tattatttta agaatgatta 86640 ggattgataa gggtcccatg accagcatta tgaaaatgcg agagtgggaa ggacacagtg 86700 tgagacttcc actagaaaaa agtgaaagtt agggttagga catccttttt taaaattac 86760 aaatttagtc cgttttggtt tttgtaatca ggctaggcac agtggctcac acatggaatc 86820 ccagcacttt gggaggccga ggtgggagga tcacttgagc ccaggagttc gagaccagcc 86880 taggcaacat agcaagaccc tgtctgtaca caaaatttaa aaattagttc atcggggtgg 86940 cacacatcag tagtcccagc tactctgcag gctgaggtgg gaggattgct tgaacccagg 87000 aggtcgaggc tgcagtgagc tgtgatctca ccactgcatt ccagcctggg tgacagagtt 87060 agattccacc ctctcccacc ccggcaaaaa aaaaaaaaa agatgcaatc aaaggggctg 87120 ttggccagca atggcagcag cagcggcggg cagtctgccc aagtgtctta ggaaccaaaa 87180 gcaaataaaa gtgtttccat atatgccacc agccaagtgg ccatcctaat tcagaaagaa 87240 gctagccttt gagtgtctgt catggtgcat ccgtttcagt attatttcct aaaatgagaa 87300 gcccctgtgt caacaagatc caggggctgg agcccaatgc caagcctgtg ttgtccccag 87360 cgaccctgca gctgctcgct ctgatgtacc ctgtgccatt caaggagatg tggtccagga 87420 aagtgagcct catggtttc agaaagtca ttgttctgtt tacattttca taaaacctgt 87480 taaaatagc tccccgtctc aggctttcag cagtaacagt gagctgactg gcaagttcga 87540 tgttagctcc cgggacactc agcagcgatg gtgagcattt tggtttcctt aaggcccagc 87600 aagacttcca gggacatctc tggtgaagcc agaatggaga caccccgtgac ctcaggctga 87660 aagtcactcg acattggtct cttgtgttga aatcaggcat tcctatttct 87720 ttaataaca aaaccactaa ttgccactca atgctgggaat attttgggtc acctaatcat 87780 agatttctca gggcatcaat actcaaatat aggctgatta tgccccagtt caaatgggaa 87840 ctttaacag agtgcatttc ttgcttgctg ggtttcaaca gacatcagcc aaaagaacaa 87900 aagagatgtc aggacagatt ccaggagtgt cggagcacat gtgtggcacc cgctccctct 87960 ggcagcgaat gtaggaagtc gccaaattta cccactcttc aacaagtcat tgtttaaaca cggtttttca ttttctcaac ttttaatagc aaaaagtgcc aaagtcctca gagacctaac agccttggtc taccgtgctg accagggtga aggcacggcg agggactcct cccagacgtg 88140 cctcttgtgt gccagctggc tgtggctcgg gagcagacgc aggcctctcc attgtccagg 88200 ggagcctggc ggcgcatccc tcctctccca cctcctggca cttccagctg ggtgtcccac 88260 atgttggatt ccgtccccac cacacttcca gagaccggag aactgtgcag ggcctaaggc 88380. cgtttggatg aattgtcaaa acaagatgct tccagttaca gcggcaggag cgggactggg agcacgggct gacggctgct ggtgcctttc ttcccacctc gcttgcctgt ttccgcttga 88440 cccttcctcc agctccgatg agaagagtat aaagcatctt cctaacgggt gtgtttgcta 88500. tacgaacata atggacgtga agtggggcag aaacccaga ctcagcattc aaggatgccc aggagagctg tccctgtttt aaagagctgt gttttgtttt gtttcgcatt tagagagcag 88620. acaaggcacc cttctgctgc gctgatacgt ttcttacact gggccatttt agacccccag 88680 ggaaacagcc ttcctggagc gttgtctgga ggttccaggg acagggcagc ctcccagagc 88740 cgagcaagag ctcaaggtac aaatgagaga tttgctatac cgtgagaagt caacaactta 88800 gccaccactt ccccgcaatg gaccatgtaa caaatacctc agcaggccct gcaaaaggcc 88860 atgctagagc tgaggcgcac agcctgtggc ctctgtagtt agggcaggtg ggatggagac 88920 tccttgagtg cacacacctg agcctgccca cacacagggg agcagcatct cgtatgacgt 88980 ctggaaggaa cttcggttgt gtaaagggag ccttgaagat acgtgcaaaa ggtgctaccc 89040 caatttggtg aaactgacat tgggcacgtc ttgggcttag gagaagcggc cgatggtccc 89100 ggcctgcagt gacaaacccc cctccccgca ccgcccccag caccccctct cctcttcacc 89160 tcttcctgct ggccacgagg aagccacttc ctcagagaga ccctaccaga tgcggatgga 89220 aacagatgca ccaaagcaag ccctgatgaa accgcgactt cctaaggtct gtctcctctg 89280 aacttgcacc tgggcctctc tgtgtttggt tccaagcact tcccacctca aactcccatt 89340 ttcaaaccac tgtatctctg cgcacatctg ctacttacca gccgcataca tgatggaggg 89400 ttttttggtc ctgatccagt ggccacacct gtctttgaaa tgtctcactg aactccagtt 89460 ttaaaataga ttcattgctt caacacagca agcccaatgc acccagctaa gactggcttg 89520 accgacagcc tggcctttgg tggggggctt cctggggcct ggggaaagct ggccaccttc 89580 aacagctggt acctcttcaa cagtgtggcc tttcaaaatg cagatgccac caggagaagaa 89640 tgcccacagc tcaccaccta tggatgccat ggctctgggc agctttcaaa gcaggttcct 89700 gtggtctcct cagctgtttg aggggtaac agcaaatcag cctccatttt aaaatgaaaa 89760 caccagcctc cagatgtagg gcctgctgggg tgttgctagc cgctggtccc caggcacggt 89820 gcactttctc cacctcctgc agcctccctg ttgtttctag actcttgcac ctggtgagtg 89880 caaggatagg tgacccaggg gcctgcagcc ttgtcctcag ctcccatctc ctggactgcc 89940 agcctcaccc tctgcagtta gcatggttgg cctgatgcag ggatcccgag ggattacttt 90000 ttagaccttc tttcacattc agaaaagtag tatagattca ggagaggcaa gaaaattatg 90060 ctgtccatag aagtcaccca tgaagactga tgccaccacc tgaaggctca tgattgttaa 90120 aaatgtccac gggaacctct cgtccacagg aggtttgtct caacacttcc catttttacg 90180 gcattggcat tgccaagcat ggggaagtat ctgctcttct catgttaaaa gtggcccagc 90240 ttttcttaac tcagtccaag ctgacttgtt taggctcact ggaatttctt accaaccaaa 90300 tatttgcatc gagcaaaggg ggctgtgtgc acctccctaa tggcagcgat gatggctgct 90360 gtcattcaag cccatcttca gacgtcacag tctggaagtg aaatgtccac aaacatctgt 90420 ggcagaaaag gctatacgga ccacccagtt gtgctcagc tttacagagc aggaagggt 90480 tgtggcaaat aaatgattaa cctgcctcga ctgtgctgag ggcaacaaag gccatctcac 90540 caaaggatta ttcgatgcca ttaaatcatc ccgtgacctt cctgcttccg agtccatggc 90600 ctttgcccag ggcatgtact cccctgagag gccttctgcc tagaaagatc tatgactggg 90660 ttccaaagtt gaggcctagg tttttgctgg gatttagata ttttcaggca ccattttgac 90720 agcattcagg aaaacggtta ttgaccccat agactagggt aagaataaag gcaataaatt 90780 tggtctgact cagaatatag gagatccata tattctctg gaaaccacag tgtacactaa 90840 aatgtgaaat tgaaggtttt gttaaaaaga aaaagataat gagcttcatg ctttgtttaa 90900 ttacataatg atttccatta cgctatttct gtgaaatgca gcaggttctt aaacgttatt 90960 tcagtggcat gggctgggaag cttatcacaa aaagccatgt gtgtggcctt atcagaacag 91020 aaagagacag gctggtgccc aaggctgctg cctgctccac cttttgccag ctctggacat 91080 ctgaggacgt cccggcagat ctggaatggg gccctcaact gaccatttgc ttctcagaat 91140 ttcagtttga gacatgagag gtataatcag ttacttttct ccccccagag aaaccctttt 91200 gtgaggggag aggagctatg gtatgtggtt cagctgaaac acatacaact gcatcctttt 91260 ggagtccttt gccaacaaaa acagaccaac agaccagatg gtgtccatgt tcaatatcat 91320 gtcttgatgg acgcagctga tgacctcaaa tacttgagtg gtctcatggc tgttagatgg 91380 attatttga aaaaaaaaaaaaaagagaaaaaaa ttgatttta catcagagat 91440 agcaaactaa gacctgggga ggggggtcag cttttattt atttatttt tttaagtttt 91500 gctagttggg tcaatgtga ggaggaggga gtctacctgc cacctctct cttgccccctc 91560 ttctgcccac acatccagca tccaaaatcc attcatttaa tgaattgata aagtgccgtg 91620 caaactggtg cacaacagg cccccagtcc acgcagcctg gctcctagga aaagtggtga 91680 ccggggcgtgg gggggcatgc cgcagccctg ggacacagtc gggcaccttc cccggacccc 91740 caggccttgg ctgtgcctca agtcagagag ggtcagcctt caggccccgg agacgagtga 91800 ctggccgatc atttcacaat aaatcactc acttttggca acttcacttt ttttaggca 91860 cagtcagttc cttttctcat gtacctcaca aagatgaag accatgtagt actcttttg 91920 gtaaagttac agtgttcatg ttaaatatca cttttttcta cattgtgtgg taaaaagaac 91980 tacgttaata gctatatctt aaatactgtg atttgacttt ttgaaaaata tcctaataca 92040 atattttac taacttaca tcactcatttt aagaaac atttggattc tttgaatc 92100 agtgttaatt gactcatatt cttaaaagcc tggctcttga ccctattgga aacacaaagg 92160 aagctgaaat caaacatcta aaatacactg cgtacacgtg tgcgtgcaca cacacacaca 92220 cacacaca cacacagctc ttcatttctc ctgagccatg cagaatttac tttcaatgtg 92280 gaaatctgtt ccctttacca cactgtatat gcacagagca caagagaggc tatctctagt 92340 cacttccacc agcgaggcct tagactccgt attagaggcc accgatttca tacaacagtg 92400 tttcgctaaa gacccttcac tattcttgtt tagtaaatag ctgtctgctc ttcagggaac 92460 tgttacctat gggttattac caaagaacgc tggcaattgg aaatgtcctg atggaaattc 92520 tttgcacgtg ccggttctct ggcatcctcc aggtggccca acccaaagca gaaagcagaa 92580 accacagacc ccgtgagtct ccccatacct tgtttccaat aacttggcaa aacttcttgg 92640 tgcatattgg ttacaccctc tgggattcat aatgccatta ggctaaaacc ctaagagaga 92700 gggttgacag aaacacacgc gagaatgagg cagatcccag agcaaggact gggcccagac 92760 tctccacatg tgcttacta gtgagtgcct tatactca gtattttggg gcttacagct 92820 tcttatttgt gctaaaaagg tgcagttcca aagtaggaac tgccacag gccccagcat 92880 cctctctcca acttcatacc tctctcctgg tggggggc gggcatccag gacctccgga 92940 atcaggatg tgcagagaag agcgaagta atttcttag tcacatgaac tgattggttc 93000 caggcaatta gaaaatggct aaaataac cttaattta aaaaaaaatc ttgggtcttc 93060 gttttcctat taggactg aactgaccac atgtattgat ttatatcctg atatatggg 93120 aacttctgtg tttgggt cctactgtaa gactgatgaa tgtacagagt taatttcagg 93180 gtacagtttt gccttaatgg ttttaaaaaa taaactattt tttaaaattt t 93231 <210> 3 <211> 15496 <212> DNA <213> Humans (Homo sapiens) <400> 3 ggctccaccc ccaagccagg cgaggcaggt tccgaggttg gaacacctgg cgagtccctcg 60 gtgtcggtgg ccggcagtca tctcgcggcc gttcaggtga gggggttgga ggagtggctc 120 atgagcgagg aagggggagc aggcgggctc ccacccggtg ctccgtgaga tcgaggggag 180 cgggttctgg gtgcggatgc acgcgctggg cgggacgctg gcagtggtac ccgagacggg 240 gcggaaggag actggagtga aggtgggcct aggctaaggt acgtgctaga aaggatgaaa 300 acggagtgaa attcttaagt gatggaacta ggctagggca tgtttcttgc cctttaaaat 360 gtgttgtctt cgggagacag gacgtagaag atagttgcag cacagggtga taggctggcg 420 aaagttatac aaaagcagga accactagaa ggaggtaaga tgtagtgtgc tttgggagta 480 gtggggttgg gaagggcgtc cgagaggagg ttactgaagg atgactagga gttgaatggg 540 aggacatcac ctgtaaggga acgatatttc cgtgggcaga gaggaatgaa gcagtagcaa 600 ccatgagtga tcagatactg caaaaatgtg aagtgtagga tggcgagaat gtaagaaatg 660 aagagtgaag aagtctggaa gggcctcgtg tgcatcaatc acagcggggc ttgatcttta 720 tgcttagggc aagcactccc ttgaactttg agtgttttaa ggaggttatc tctgatgttt 780 aaatttatat agatcgtggc attgcatctt agaaataagg tttaggaagg gcaagcttgg 840 aggcagggca agtccagaaa atgaggagc tggtgaaatc cgtgttaaag tgccaaagga 900 cagagactgg ctgacagcta aacttcagg ttctgagaa tccacaata actaaattta 960 tctagtcaac ctgttccaga acaggcttcc agtcattag gttgcccaag atgagtaaa 1020 ggaaaaggaa attcaattt ccagacctt gttcccctc tcctttaa ttccttgttc 1080 ggttagcaac agtatatcca ttccctcgct ccttgtga aagtaaattc ctgaatgtta 1140 actaaaccaa gtgtttctaa attgggtag agtttgaga cttaaggcag cagaatggga 1200 gagacttaa acgttatgtc tgagattag gcattaaagg aggcctagta ttggcgggg 1260 ggttgtgagg agcacatact gaacctttgg acctgttgag tgagttcatg tgcctctgaa 1320 ctctctgact ggatatgacc agtaaacttg gataattaga tcctggagtt tagggag 1380 ggctagagat agagatgatg gatgtcagca tattttaa acagaaaata gttagatca 1440 cccagacaa tctggaatcg ttagaaggga gtaggaagg cattattggg aactttcca 1500 gcttcaattc tcatattttt tctaatctcc tggttgagtc ttggattg ctgttctctc 1560 tatgcaaaac ccctcccttg accctctctc cctcactcta ttttttaatt tgtcacctcc 1620 ttctcctgtt ctaggtctca gtttagatag cacctttctc tagaagttca tagcactgtg 1680 tattcccccc tttattgttc ttatcacata atttttgatg gtttggacac tagttgttat 1740 tcctcactaa attttatgtt ttatgaactc aggggtaagg gcaccagcta gcacaatgaa 1800 tgcacaatac ttgtcagagt gaatgcattt aagttccaag aaccaaggaa aggcggtatt 1860 tcaagaagag aagtatcaaa tcttccagat tagtcaaata aactccaaaa aaaaaaaaaa 1920 aggtttattg gatttggcag ctggagatcc atagcgattt tttttttttt tttttttttt 1980 ttttgagacg gagtctcact ctgtcgccca ggctggaatg cagtgtcgtg atctctgctc 2040 gctgcaacct cagcctcccg ggttcaagca attctcctgc ctcagcctcc ccagtaggtg 2100 gaattacagg catacgccac cacacccggc taattttttt gtattttttt ggtggagatg 2160 tttcaccata ttggccagac tggtctggaa ctcctgacct tgtgatccgc ccacctcagc 2220 ctcccaaagt gctgggatta ccagcgtaag ccaccacacc cagcctcctt agtgatttta 2280 gtaagagtaa gttcagtgca gtgatgacaa tegatgcag attgcagttg ctagaata 2340 aacaggaaat aagagataa agacaactcg tggaatacct ttcatagag cttaggtaaa 2400 ctgtaggaat tattctcctt gtactctaat acttattatg ggttttatt atattatag 2460 tgtaatataa tggatgagtg catgggcttc cccacttagc atttgttaag cattaactta 2520 acattaagca ttagactttg ggcaagttgc ttaatcttc taaacctcag ttattttac 2580 tataaaatgg tgataaaata atacctacct cacgaaggtg tggtaggat taagtgaaa 2640 atgtagagag caggtagcat gctttgaaca cagttctttgg cacagaaagt gcccaataat 2700 tgttagtttc ttgtagctat tacatgccag gtcctgtgct aactaagcgc tttatatgca 2760 ttgtctcttg gactcattgg agacctact gttttaattt ttgctgctga taaaactgca 2820 tcacagagag gttacctaat ttgcccagg tcacaggaca ggactagtaa gtggtcttgg 2880 ttcattattg tcaatttac taatcacctt gagaaaaatt agatggat ggttgcctta 2940 ttttacaact tgagatga tgagacat tttggtgcag gtggggagcc agattgcag 3000 tagctcagtg agttgtgtgg gtgagttaag caacctttt tattcttttt tttgagacg 3060 gagttttgct gttggtgccc aggtagagt gcagtcacag cttactgaaa cctccaccctc 3120 ctcattcaa gcgattcacc tgaactcctg accttaggtg atctcccgc atcagcctcc 3180 ccaaggtgct gggattacag gcgtgagcca ccatgcccag ctgagttaag caatctttat 3240 gtagagctct cctttgagaa agaagttggt tggttcaag aagataaat gggacagtgg 3300 cttggaagg gtaatggagg ctaggaggt gtttatcaac aaggagat gtaggctgggg 3360 cgcagtggct cacacctata atccccac tttgggaggc tgagatggga ggattacttg 3420 agcctaggag tttaagacca gtctgggcaa catagggtga cccctgtctc cacaaaaaat 3480 taaaaaaatt agccagggt ggtggcatgt gcctgtgtc ccagctacga ggggctgagg 3540 tgggaggatt gcttgagcct gggaggtcga ggctgcaatg agccatatt gtgccactgc 3600 actccagctt gggtgacaga gtgagaccct gtctcaaaaaaaaaaaaaaaaaagaaa 3660 agacgtgaat gtgttttag acctgaagga atggattcca tgaagggaga aggatgaaag 3720 atgggaaagg ataagtgatg gacaagttct tgaggtaaga taagaacaca ggagaactag 3780 tcagtcttag aggaaagaat gaatgagcaa agaaatttta aggcctgtaa tgacacagga 3840 tggaacacta tagtcactgt ggtgtaagtc atttgagatg agtaggacag aaggaggacg 3900 gcctgaagtg aattcagatg cctggaggag ttggctaggt tctcaatatt ccttctgtag 3960 aatgggataa aaggtcagtt tgagaagtgt tgggggaaggg gacttttaaa gcactattta 4020 gaatgcttct gaggctttaa aatactcatt tttaaaatgg tccaaaaaat tcataaatta 4080 gaagcagcag tggtgaaacat ttttaggaaa gtgacccttg agaagtttat tttttggtta 4140 gtgacctatt gagcttattt attaggtaag tagaacatgc tcatttaaaa agtttaaatt 4200 gtgcaaaaga catatgtcag atttttttt ctgtcttcca taacactatt tcctaccccg 4260 ccgcgctctg tcttccgtaa cactctcccc taccccgtcg ccactctgtc ttccataaca 4320 ctgtccccta ctccaccaca ctgtctccta ccccgccgag ctgtcttcca taacactctc 4380 ccctaccccg ccacgctgtc ttcattaaca ctatctcctg ccctgccaca caactctgtt 4440 ttcctagaag tcaccagtgt gaatttttcc ctttatccat atgtacattt tttgtttctg 4560. tgtgtctgtg father tgcataaaag tgcatagata aaatacatat ccttttcaaa aaatcttaag tggggctctt gctatgcata ctgttctgta acttgttact tggattaaca ctgtatctta gacatctttc tatgtaggc gtatagatct tccctgttct tttaaatggc tgtataattg tctatggaag gacttaattt atttaaccca taccttgttg atggcttatt tgtgttttgc ttttattttt tcctctttgt ttttgctgct acaagcaatg cttccttcca tcttagcgga tctgtctttg tacccttgaa tgagaaagtt gctggatcaa aggatgtatt cattttgaat tagtgttgc taatttttcc tccaatgata cactgatgta tcccccctgc ccacagtgtg tggtcatgcc tgttctctca ccctcttacc attackc 4980. ttttaagat ttgctactca ggctaaaagt gtctctttgt tttagggtgc atttcctcat ttaatgaagt gaagattctt ccttgtttag tgaccatttg cctttatttt tctgtgaact gcttgtgaat ggcatttgtc gttcttctgt tgtcttttta gtctttttc taaagcacac tttgtagccc tttgttgtaa aatgttggaa atatttttcc cagtttgtca tttaatcttt 5220 gactttgtct ttctattccc footggagg tacttaattt ttatatactc atatttggca 5280 ggctttttct ttataggttc ttttggcttt aagtgatact tttaaaccca gctattgctc 5340 atttaaatta gaaccttttc catgagaacc acactgacga tttctttaaa tatagcttga 5400 aaaaattttt cccctattgt tcttttagct attgttcttg aaaataatgt gttttttaaa 5460 ggaatatcta caaatagaaa tggtgatgat atccagcaaa tgttttaaaa tggtgtaaaa 5520 ccatttgtac tcctttagta atttttggt aaaaaattta tactccttta gtaattatca 5580 tttttaaaat gatcagagga tgcatttttt aactgtttta ttttttgaaa gctcattgtt 5640 taacttatta tatatgtatt catttctaca gaattataag gctgtctgca gagatttgaa 5700 aaatggcaac aaatgaaagt gtcagcatct ttagttcagc atccttggct gtggaatatg 5760 tagattcact tttacctgag aatcctctgc aagaaccatt taaaatgct tggaactata 5820 tgttgaataa ttatacaaag ttccagattg caacatgggg atcccttata gttcatgaag 5880 ccctttattt cttattctgt ttacctggat ttttatttca atttatacct tatatgaaaa aatacaaaat tcaaaaggtg agtataaggg actagaata gaatattatc attackgttg ctgaatattt taaaagtaca tagggctttg ttttgtgagg ctaaagcagt gatatccaat agaatatga agccacgtat gtaattttaa attttctagt agaatacata gaaaaggtaa aaagaata ggaattaat ttcataatgt gtatcattta gctcaataa tgtaaactat cgctgggtgc agggtccatg cctgtaattc cagcactttg ggaggccag gcaggaggat 6240. tgcttgaggc caggagttca agaccatcct gggaacata gcaagaccct gtctctacaa aaaagataca aaaataccca ggcatggtga tgtaagtcct agctacttat gaggctgaag 6420. gcgcactt actctagcat aggcgacaga gtgagacctt gtctcaaaaa aaatagaaa taaatgtaaa ttattatttc aatcagtaat caaattctaa aaaatactta atgagatatt taataagtct ttgcaattcc gtgtgtattt tacattaatt ttagtctatc tcaatttaga ctagccatgt ttaagtgtt tggaagccac atgttactag ttgctcctga attgagcaac acagtcctag gtcattattg ataacatttc aagaatactt tgttaaattg 6660 ggctttaagt agatgtgatg gttatctaac ttaagtttat gaattttaat gtttaagcta 6720 gctgggaaagg aaaggtgtgg tgatttgcgc atattttgca gttcacccca actctatgtt 6780 ccagtaaatc taagggactg ttaatacact acgaccttga tcagggctat tcaagttttt 6840 tttccctaaaa tatatggtag gtagttctgc agcattcgta tcatcccaaa taaggaggtg 6900 atgctcctcg tttctggata tttgcttcat tgcactaaat gttgagaggt cgctatgtac 6960 atgacaaggt gaaatctcat atgtagcctg tgagcttgac gtgagaattt ggagtagctt 7020 attagaaaga tgaattattt gttagaattt gtaagctgat gatagtttct agtgtttgct 7080 gtttactttt cataaaaagt cattccaaac taaaactcag gggcacacag tcttggtaga 7140 aagtagacca ttgagagtat tcatctatgg aaagtaattt acattcactt agtacaattg 7200 gccctccata tccatgggtt gttgtatcca tggatccaac caactgcaga tcagaaatat 7260 tcagggaaa aaaattgtgt ctacactgaa catgtacagt cttttttttc cttgtcatta 7320 ttcaaaatga caactattta tagagcattt gcattttatt aagtattata agtgctgtag 7380 agatgattta aagtatga gaggattcgt gtaggttatg tcaaatacta tgtcatttta 7440 tatcaggcac ttgagcatct tcagatcttg gtatttgcag aaagtcccag aaccaatcct 7500 caaaagatac caaaggacaa ctgtatatat tttggatggc agtctgtaca cattctctgt 7560 tatcattctg ttagtttcac agcctctccc agagtctcac tttaagcagg tattaatatt 7620 agtcctctct ggggataatg caggggtcag atgactgtgg actccaggcc aaaggaaa 7680 agagcaaagg gtaaaggcga aggaataa aataggagg gccaaaggag agtactctgt 7740 gaccctcaat taaggtcaca gaagctccaa agtgctttt aggaaagcag ctgctttgaa 7800 aggcagaatt aagtttggac gtctaagttc taatgcacct ttagggtgat tgtggctgcc 7860 gtgtttcacc cagtgattta tttatagggc ttatcattg taattcattg tatggctggc 7920 caggcaaaag catcctttt ctccttcact gcagtttgta actgactcac tggttagaag 7980 tagtaacctt tgcagagaga caaaggactt tctcaggcaa gggtatatga gcagctttaa 8040 atataatgt ggcaaggaa agaataagct gtagtctagt tggtcagagc tagttgttta 8100 tgaacagatt gtaggctgg ataatttgac ttcaagctg tactcagcaa gtctttatgt 8160 ttcataacca ttaaagtcca tgctttgagc atttttgata aaaaatgtga ttttaaacca 8220 ggactagttt tcacaagtta aaggagtttt aaagaaacc aaatattgg tacaattta 8280 ttacaggtttt atgcattcg aaggcagata ccctgattta cattgaggggt atcattgtt 8340 taagataaa tattttgagaa tatatatta catatgcaat aaatgtttttt attcttaaaa 8400 ttgtcgaaaa gatagaaga agttggtggt ggtgatgaaa tagtactaaa gactttctgc 8460 ttcaacag aacagacaac tggagcta atgcacatcc ttgctagtta ggcgaaaatt 8520 tcacaggaat gaaaagtaa agcagacttt gcaggactcta ttctttaaaaaaaaaaaaaaaaaaaaaa 8580 acatacatct tagtattct ccaaaattt tcccaatct taaatgtact aaaaatatta 8640 tttctgaagt tgtggccct tgtaaggta ttcctttata ttagtacag ttatgcataa 8700 agaaagtaaa atatggtaaa ctttcatatt gcactaggta tgaatttgta ttgctaactg 8760 tctttgtaac taatttatgt atactgtaaa tgtatagca tgtgatttta ttatagttga 8820 ttaactttgt aatttctgta actgcatcga tatcccagtc tacctggaaa attaagtcta 8880 ttaaccatag tgctgtagg agacagtact attgccaact gaagcctgaa tccttcattt 8940 atttgtccc cattacaga gtggaggttt agaggagtgg ggttagata tgctcagatt 9000 agaaatacaa aggcagctgt cagatcctcc cattttattg tgagaac tgagttgtaa 9060 acatcacaag agctagttaa ctggtgagta gcagccctgg tattagagca caagtctctg 9120 gattgattct tagttcagtg cttttcctat tttgtcagg agataaccc ttaaagaatt 9180 tcaagaacag agctggatct ggagacctag attttagtta gtccaacttc tgctaataac 9240 tgcgtgtgtg accctgccca agctggttga cctcttggg cttctgctga tgcgcagtag 9300 ttcccgtact ttggatatcg tggttcatt aaagagtttt tgttggcgga tacctgaatt 9360 tttcagcagt gatattaa aaagcaat aactgatatt tattgtcacc atcgttttgt 9420 taagcccaaa gcacttttt aagtgcagtc ctataaattg atacattta gttagtgttt 9480 gttttgtttt gctttgtttt ttataatgac ttgctaagca aatgggtatc ctgatgaggt 9540 cttaacgaac atcccatgtt gatctaactt ttctcatttt gacttgaatc tgtgaactcc 9600 ataatcagga catatctgtg tacttctcaa ctcagagagt ttataattct gtcattggat 9660 ttgaacaaaa gtgcatttat ttgttggaat gaataccact gagtgcctgg aagcatcgac 9720 ttactgtgta aaaggcttcc aatgcttcgt atacaacttc ttcaattgtg gacacccaac 9780 agtaatctta gcatattata tttcttcttc tctgaaactt ctggtaaaag aagtgaagtg 9840 aatgatctgt ggcagcaaag actggagaat tattcattcc atagtgtttc ttagtttgtt 9900 tgagatcatc atggctaggc gcatctgtta acagtttctt cacctgaagt agtgatagta 9960 gttgtcaaga atttagaagg caaagattcc tgagtcttag ttatataaag ttaacataac 10020 tgacgtagaa ttaaggtcca acataaacag agaacaaatt aggtcaagtt aaactctgat 10080 agcagagact aatattagat attgtgattt ttcttcgtag gataagccag agacatggga 10140 aaaccaatgg aagtgtttca aagttcttct ctttaatcac ttctgtatcc agctgccttt 10200 gatttgtgga acctattat ttacagagta tttcaatatt ccttatgatt gggaaagaat 10260 gccaagatgg tacgtagata aaaatttggc tttataccc aattgtggct tattcagtta 10320 agttatactt aatgtttacc cgttttctta attttagtta atgtttgttc taaactttgg 10380 aagtaaataa atagtagaaa agtaaccac agtaaaatct taaaatgttt ccatttttc 10440 atcttttaaa tattttattg gaaggtgagc ttctagtatc agaagtttcc ataacgtctt 10500 ttgtatgttt atatacatgt ataagtgctt atgttgacaa aaatatatta cattttaatt 10560 ttaaaatgaa tgaaaatat gagaatcatt tatgaggttt atagaaattg tgtttacatg 10620 aacaaaaata tgtatgtgta tatatatata tatatatata tacacacata tatatataca 10680 cacacatata tatactcatg cgtcacttaa cggatatctc ttgagaaaag tgtcatgagg 10740 caagttgtgt gaacattgta atgaaatgaa attggtctaa tgggcagtct ctttaacctt 10800 atatcaagtt atgtagctgt atctggtggt tttgagaatt tatttatgaa tatatccaat 10860 taggtcaacc tggtaagtgg gtgggtggtt ttatgtaatg tctcaagcag tgatcccaac 10920 taaaagtctg gatagtttaa gtaaaaatta tttcttacac attacaacat ttttatctta 10980 aaggtatttt cttttggcaa gatgctttgg ttgtgcagtc attgaagata cttggcacta 11040 ttttctgcat agactcttac accacaaaag atatacaag tatattcata aagttcatca 11100 tgagtttcag gtatgtgaga gttatattta attctttctg ttagaggcaa aatgtctatt 11160 ttaattgcct gagcattttt ctaaaattgt tggtgacgtt tttattttct tttcctttgg 11220 catgattatt aagaacaata cacacacata caaacaagcc atttctacac attgttttca 11280 ttatttaaat ttcatggtaa attgagatct gaaagaaaaa tattatatga aagttcggac 11340 ttccatcctt gtggacagtg ctacactggc acagctagat cctcacattg ctaactccca 11400 caaaaacagt aacttctatg agcactgctt tttttttttt tttttttt tttgagatag 11460 agttttgctc ttgttgccca ggctggactg caatggcatg atctcagctc actgcaacct 11520 tcacctcctg ggttcaagca attctcctgc ctcagccttt caggtagctg ggattacagg 11580 catgcgtcac cacgcgtggc taattttgta tttttagtag agacaggatt tcactatgtt 11640 ggtcaggctg gtctcgaact cctgacctca ggtgatccac ccgccttgga ctcgcaaagt 11700 gctgggatta caggcgtgag ccaccatgcc cggccaatta gaattgcttt gatgtagctt 11760 tgtcaactgg tttgtgagt atgttttgca ttgaccgtga ttacatggtg tgccaaatca 11820 agcctctctt tattagaaga acaaatataa atacttaagt caaaattaga gttcaagtca 11880 attatttaat gcctttatct taaaccatca aagacagcaa gattttatat ccctagactt 11940 ttgatgtgga gtaaggtatt tttattgaga attgctagta ttatttataa gtgtatgact 12000 agataaatca tcactacata tagaatcaat ataactttgt aaaactttat gcataatag 12060 gatatatata ttagtgaagt ctccagtgaa gcagaatcat tggggtatat atatgcagag 12120 agagatttat tttaaggaat cagctcatgc aagtgtgcgg ctgtcaagtc tgaaatctgt 12180 aaagcaggct acagactaga aatccaggta agaattgttg cagccttggg tccaaattcc 12240 atggagcagc aagttggaaa ctcaggcagg gtttcagtgt tgcagtctcg agaatccttc 12300 ttcaggaaac ctcagccttt tatcctgaag gccttcaaat gattggatga agcccaccct 12360 cattatgaag ggtaatcacc tttactcagt ctactgattt aaatgttaac aacatctaaa 12420 aaataccttc acaacaacat ctagactggt atttaatcaa acagttggat atcatagcct 12480 agccaagttg acacataaaa ttgaccatca caatagctaa gaaattaaga atttcttatc 12540 tgtttgtctt aggctccatt tggaatggaa gctgaatatg cacatccttt ggagactcta 12600 attcttggaa ctggattttt cattggaatc gtgcttttgt gtgatcatgt aattcttctt 12660 tgggcatggg tgaccattcg tttattagaa actattgatg tccataggtg agtattaatt 12720 tctgttcagg tataaagcat aatgaatatat atttattttc atggccataa gattatcata 12780 tttctaagga gactaatagg agaagttaat cttcttaatg ttatattaag aaaacataac 12840 tgttggataa aagtttaaat aatagatgtt tttacattct agcctatgct gttataattt 12900 ttatagtgat aatgtgttat tagggcaagt atatattcag gaccagcaat ttccttatcc 12960 ttctgtaata aacctaaact taactcatat ttgaaaaaaa tatcaaagca ttcagccttc 13020 cttgaataag actttctaat ctctactgtt cagcactgat aaaggcactt gcaagatgaa 13080 actactactt gtaacacata catatttcaa atgcatcctt tctgttgatt ggaagacatt 13140 ttgtggtaaa ttattatat tgaatgcctt cttaaatgct tatcctaatt gttcattatt 13200 ttttaattat atgttcattg cattttgact tgggacatac ttctgtactc atgaatgcag 13260 aatatcaaat tctaagaatt atttttaaag tgctaaagta gcaaaattaa tgcttctagt 13320 cctaggcaga gaatattctt ctgtagaaaa attgtaattg acatttcttt ctttttttt 13380 tctatccatt gtttctttct gccttcttc ctctaagctc ctcaaaggaa gagagggtta 13440 gagtgattca aataagtata actggatgtc tgattgtaga tatgtagttg gaaataaagg 13500 agcatacttt aaatgggact ctttttgaa gccatttgtc ttctgccaac tatagaaaaag 13560 tacactggta ttttgattaa ttgtggtaca tttgattcca acttgtcatt gcctaaaaaaa 13620 gtaaatgaag ttgctataca gggattcatg ggcctgccct ttttaatact tgatactaat 13680 tttatgtgac tttcctaaaaacatattt agtattttgg gctttatta caactgttat 13740 acatgatggt gagaagctt cctctaaaac aaaagaaa atttattctt aaaaatctgt 13800 gtctaaagat tcattactat aatccgtctc ttcatcatt catatatttt atcataaaat 13860 aaatgatttt cttagtttttt ttaaggattt ttttcttag agtggttttct agaataca 13920 ccattttctg tgtttgctgt ttgtgaacac ttagaaataa agtggtctag gcaaagtggc 13980 atgttatcta aattggttaa tgtgaacaca tgattata taaaaacaac atcatttga 14040 gatgtattta ttccttaata atctttatca ttttgttttc agtggttatg atattccctct 14100 caaccttta aatctgatcc ctttctatgc tggttctcgg catcatgatt tccaccacat 14160 gaacttcatt ggaactag cttcacatt tacatggtgg gatcgaattt ttggaacaga 14220 ctctcagtat atgcctata atgaaagg gagaagtttt gagaaaaga ctgaataat 14280 atctcacgta aaccttcctg aaagataac gttttcctga attcagaac tagtagcta 14340 cattgcttct ggagagcaga aataagcatg tcttctggct actaagtgat aaaaagaaca 14400 ttaacaacct ttaattacct tcctagtggg aactttttct actttaccta caagttctat 14460 atatgtagaa atgaataaat atatatttaa gtacagtttt catgaggaag ttttaaaaga 14520 ccatgttcct aagcttccaa gaaggttttg gatactagaa gtattaatct atggctttc 14580 tcccagtaaa accataggcc tgaagttcac attgggtcttt taaatctttt agatatatac 14640 tggtcatttc agaaaattct tcatagtggt attggcctta tatttaactt tttttttatt 14700 tttttttga gacaaagcca cactctgtct ccttggctgg agtgtggtgg cacagtctca 14760 gctcactgca acctctgcct cccagttcaa gcaattctttc tgcctcagcc tcccaagtag 14820 ctgggattac aggcacccgc caccacgccc agctaattttt tgtatttttg tagagatggg 14880 gttcacgat gttggccagg ctggtctcaa acttctgacc tcaagtgatc tgcccacctt 14940 ggcctcccaa agtgctggga ttacaggtgt aagccactgc gcccggcctt tttaacttta 15000 aacatgtttt agaattcacc taaagatcaa aatatcatgg attgaacctc atcaattgat 15060 agcagtgagt gactgaagct tccaaatcaa gaaaagccgg caccaagaac ttccattcta 15120 atctagagct gaccagtttg agctgattct ctctttgaag agtccttctt gattgcagtg 15180 cagtactggc atttctgaat ggatgtaagt ggagtatttt agtctaaagg cttttcaaat 15240 tacttgaatt tttttaaaaa ttgaggagct ttatttctat ttacccttcc atttttgtat 15300 atcaaatttc cattgtcatt aaaaactgta tcttgaaact ttgtgaactg acttgctgta 15360 tttgcacttt gagctcttga aataaatgtg atttttgtgt gattatctgg tttccagttt 15420 taaacattaa ctgtcacctt ttattcttaa acttgaaagt acagaaatca ttaaattatt 15480 aagttgtaca ataaaa 15496
Claims
1. A cosmetic skincare composition comprising: a) A combination of palmitoyl dipeptide-7 pal-KT and acetyl tetrapeptide-11 ac-PPYL; and b) Dermatologically acceptable carriers; The pal-KT is present in amounts ranging from 0.00005% to 5%. The ac-PPYL is present at 0.00005% to 5%; and The pal-KT and ac-PPYL are present in a ratio of 10:1 to 1:
10.
2. The composition according to claim 1, further comprising at least one additional ingredient selected from: sunscreens, oil-controlling agents, antioxidants, protease inhibitors, tyrosinase inhibitors, anti-inflammatory agents, moisturizers, exfoliating agents, skin-brightening agents, anti-acne agents, anti-wrinkle agents, antimicrobial agents, pH adjusters, thickeners, preservatives, and combinations thereof.
3. The composition according to claim 1 further comprises an additional ingredient selected from antifungal agents.
4. The composition according to claim 1 further comprises at least one additional ingredient selected from: vitamins, minerals, peptides, glycosamines, flavonoids, phytosterols, N-acyl amino acid compounds, and combinations thereof.
5. The composition according to claim 1, further comprising at least one additional ingredient, wherein the additional ingredient comprises a vitamin B3 compound, a vitamin A compound, a vitamin E compound, a sugar, or a plant extract.
6. The composition according to any one of claims 2 to 5 further comprises 0.1% to 5% of a rheology modifier.
7. The composition of claim 6, wherein the composition is an oil-in-water mixture with a water-to-oil weight ratio of 12:1 to 1:1, and the rheology modifier comprises a superabsorbent polymer thickener.
8. A non-therapeutic method for treating the skin, comprising: a) Identify the target skin region to be treated; as well as b) Apply the skin care composition according to any one of claims 1 to 7 to the target skin portion during the treatment period.
9. The method of claim 8, wherein the processing period is at least 2 weeks.
10. The method of claim 8, wherein the processing period is 4 weeks.
11. The method according to any one of claims 8 to 10, wherein the method improves visible signs of skin aging.
Citation Information
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