Method for the prophylaxis and/or treatment of proliferative and/or inflammatory skin disorders
The present invention relates generally to a method for the prophylaxis and/or treatment of skin disorders, and in particular proliferative and/or inflammatory skin disorders, and to genetic molecules useful for same. The present invention is particularly directed to genetic molecules capable of modulating growth factor interaction with its receptor on epidermal keratinocytes to inhibit, reduce or otherwise decrease stimulation of this layer of cells. The present invention contemplates, in a most preferred embodiment, a method for the prophylaxis and/or treatment of psoriasis.
[0001] The present invention relates generally to a method for the prophylaxis and/or treatment of skin disorders, and in particular proliferative and/or inflammatory skin disorders, and to genetic molecules useful for same. The present invention is particularly directed to genetic molecules capable of modulating growth factor interaction with its receptor on epidermal keratinocytes to inhibit, reduce or otherwise decrease stimulation of this layer of cells. The present invention contemplates, in a most preferred embodiment, a method for the prophylaxis and/or treatment of psoriasis.
[0002] Bibliographic details of the publications numerically referred to in this specification are collected at the end of the description. Sequence Identity Numbers (SEQ ID NOs.) for the nucleotide sequences referred to in the specification are defined following the bibliography.
[0003] Throughout this specification, unless the context requires otherwise, the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element or integer or group of elements or integers but not the exclusion of any other element or integer or group of elements or integers.
[0004] Psoriasis and other similar conditions are common and often distressing proliferative and/or inflammatory skin disorders affecting or having the potential to affect a significant proportion of the population. The condition arises from over proliferation of basal keratinocytes in the epidermal layer of the skin associated with inflammation in the underlying dermis. Whilst a range of treatments have been developed, none is completely effective and free of adverse side effects. Although the underlying cause of psoriasis remains elusive, there is some consensus of opinion that the condition arises at least in part from over expression of local growth factors and their interaction with their receptors supporting keratinocyte proliferation via keratinocyte receptors which appear to be more abundant during psoriasis.
[0005] One important group of growth factors are the dermally-derived insulin-like growth factors (IGFs) which support keratinocyte proliferation. In particular, IGF-I and IGF-II are ubiquitous peptides each with potent mitogenic effects on a broad range of cells. Molecules of the IGF type are also known as “progression factors” promoting “competent” cells through DNA synthesis. The IGFs act through a common receptor known as the Type I or IGF-I receptor, which is tyrosine kinase linked. They are synthesised in mesenchymal tissues, including the dermis, and act on adjacent cells of mesodermal, endodermal or ectodermal origin. The regulation of their synthesis involves growth hormone (GH) in the liver, but is poorly defined in most tissues (1).
[0006] Particular proteins, referred to as IGF binding proteins (IGFBPs), appear to be involved in autocrine/paracrine regulation of tissue IGF availability (2). Six IGFBPs have so far been identified. The exact effects of the IGFBPs is not clear and observed effects in vitro have been inhibitory or stimulatory depending on the experimental method employed (3). There is some evidence, however, that certain IGFBPs are involved in targeting IGF-I to its cell surface receptor.
[0007] Skin, comprising epidermis and underlying dermis, has GH receptors on dermal fiboblasts (4). Fibroblasts synthesize IGF-I as well as IGFBPs-3, -4, -5 and -6 (5) which may be involved in targeting IGF-I to adjacent cells as well as to the overlaying epidermis. The major epidermal cell type, the keratinocyte, does not synthesize IGF-I, but possesses IGF-I receptors and is responsive to IGF-I (6).
[0008] It is apparent, therefore, that IGF-I and other growth promoting molecules, are responsible for or at least participate in a range of skin cell activities. In accordance with the present invention, the inventors have established that abberations in the normal functioning of these molecules or abberations in their interaction with their receptors is an important factor in proliferative and/or inflammatory skin disorders. It is proposed, therefore, to target these molecules or other molecules which facilitate their functioning or interaction with their receptors to thereby ameliorate the effects of abberant activity during or leading to skin disease conditions.
[0009] Accordingly, one aspect of the present invention contemplates a method for ameliorating the effects of a proliferative and/or inflammatory skin disorder in a mammal, said method comprising contacting the proliferating and/or inflamed skin or skin capable of proliferation and/or inflammation with an effective amount of a nucleic acid molecule or chemical analogue thereof capable of inhibiting or otherwise reducing a growth factor mediated cell proliferation and/or inflammation. Growth factor mediated cell proliferation and inflammation are also referred to as epidermal hyperplasias and may be mediated by any number of molecules such as but not limited to IGF-I, keratinocyte growth factor (KGF), transforming growth factor-&agr; (TGF&agr;), tumour necrosis factor-&agr; (TNF&agr;), interleukin-1, -4, -6 and 8 (IL-1, IL-4, IL-6 and IL-8, respectively), basic fibroblast growth factor (bFGF) or a combination of one or more of the above. The present invention is particularly described and exemplified with reference to IGF-I and its receptor (IGF-I receptor) and to IGF-I facilitating molecules, IGFBPs, since targeting these molecules according to the methods contemplated herein provides the best results to date. This is done, however, with the understanding that the present invention extends to any growth factor or cytokine-like molecule, a receptor thereof or a facilitating molecule like the IGFBPs involved in skin cell proliferation such as those molecules contemplated above and/or their receptors and/or facilitating molecules therefor.
[0010] According to this preferred embodiment, there is provided a method for ameliorating the effects of a proliferative and/or inflammatory skin disorder in a mammal, said method comprising contacting the proliferating and/or inflamed skin or skin capable of proliferation and/or inflammation with an effective amount of a nucleic acid molecule or chemical analogue thereof capable of inhibiting or otherwise reducing IGF-I mediated cell proliferation and/or inflammation.
[0011] The present invention is particularly described by psoriasis as the proliferative skin disorder. However, the subject invention extends to a range of proliferative and/or inflammatory skin disorders or epidermal hyperplasias such as but not limited to psoriasis, ichthyosis, pityriasis rubra pilaris (“PRP”), seborrhoea, keloids, keratoses, neoplasias and scleroderma, warts, benign growths and cancers of the skin.
[0012] In a preferred embodiment, therefore, the present invention is directed to a method for ameliorating the effects of psoriasis, said method comprising contacting proliferating skin or skin capable of proliferation with an effective amount of a nucleic acid molecule or chemical analogue thereof capable of inhibiting or otherwise reducing IGF-I mediated cell proliferation.
[0013] The present invention extends to any mammal such as but not limited to humans, livestock animals (e.g. horses, sheep, cows, goats, pigs, donkeys), laboratory test animals (e.g. rabbits, mice, guinea pigs), companion animals (e.g. cats, dogs) and captive wild animals. However, the instant invention is particularly directed to proliferative and/or inflammatory skin disorders such as psoriasis in humans.
[0014] The aspects of the subject invention instantly contemplated are particularly directed to the topical application of one or more suitable nucleic molecules capable of inhibiting, reducing or otherwise interfering with IGF-mediated cell proliferation and/or inflammation. More particularly, the nucleic acid molecule targets IGF-I interaction with its receptor. Conveniently, therefore, the nucleic acid molecule is an antagonist of IGF-I interaction with its receptor. Most conveniently, the nucleic acid molecule antagonist is an antisense molecule to the IGF-I receptor, to IGF-I itself or to a molecule capable of facilitating IGF-I interaction with its receptor such as but not limited to an IGFBP.
[0015] Insofar as the invention relates to IGFBPs, the preferred molecules are IGFBP-2, -3, -4, -5 and -6. The most preferred molecules are IGFBP-2 and IGFBP-3.
[0016] The nucleotide sequences of IGFBP-2 and IGFBP-3 are set forth in FIGS. 1 (SEQ ID NO. 1) and 2 (SEQ ID NO. 2), respectively. According to a particularly preferred aspect of the present invention, there is provided a nucleic acid molecule comprising at least about ten nucleotides capable of hybridising to, forming a heterodouplex or otherwise interacting with an mRNA molecule directed from a gene corresponding to a genomic form of SEQ ID NO. 1 and/or SEQ ID NO. 2 and which thereby reduces or inhibits translation of said mRNA molecule. Preferably, the nucleic acid molecule is at least about 15 nucleotides in length and more preferably at least about 20-25 nucleotides in length. However, the instant invention extends to any length nucleic acid molecule including a molecule of 100-200 nucleotides in length to correspond to the full length of or near full length of the subject genes.
[0017] The nucleotide sequence of the antisense molecules may correspond exactly to a region or portion of SEQ ID NO. 1 or SEQ ID NO. 2 or may differ by one or more nucleotide substitutions, deletions and/or additions. It is a requirement, however, that the nucleic acid molecule interact with an mRNA molecule to thereby reduce its translation into active protein.
[0018] Examples of potential antisense molecules for IGFBP-2 and IGFBP-3 are those capable of interacting with sequences selected from the lists in Examples 6 and 7, respectively.
[0019] The nucleic acid molecules in the form of an antisense molecule may be linear or covalently closed circular and single stranded or partially double stranded. A double stranded molecule may form a triplex with target mRNA or a target gene. The molecule may also be protected from, for example, nucleases, by any number of means such as using a nonionic backbone or a phosphorothioate linkage. A convenient nonionic backbone contemplated herein is ethylphosphotriester linkage or a 2′-O-methylribosyl derivative.
[0020] Examples of suitable oligonucleotide analogues are conveniently described in Ts'O et al (7).
[0021] Alternatively, the antisense molecules of the present invention may target the IGF-I gene itself or its receptor or a multivalent antisense molecule may be constructed or separate molecules administered which target at least two or an IGFBP, IGF-I and/or IGF-I-receptor. Examples of suitable antisense molecules capable of targetting the IGF-I receptor are those capable of interacting with sequences selected from the list in Example 8. One particularly useful antisense molecule is 5′-ATCTCTCCGCTTCCTTTC-3′ (SEQ ID NO. 10). A particularly preferred embodiment of the present invention contemplates a method of ameliorating the effects of psoriasis, said method comprising contacting proliferating skin or skin capable of proliferation with an effective amount of one or more nucleic acid molecules or chemical analogues thereof capable of inhibiting or otherwise reducing IGF-I mediated cell proliferation wherein said one or more molecules comprises a polynucleotide capable of interacting with mRNA directed from two or more of an IGF-I gene, an IGF-I receptor gene or a gene encoding an IGFBP such as IGFBP-2 and/or IGFBP-3.
[0022] In accordance with one aspect of the present invention the nucleic acid molecule is topically applied in aqueous solution or in conjunction with a cream, ointment, oil or other suitable carrier and/or diluent. A single application may be sufficient depending on the severity or exigencies of the condition although more commonly, multiple applications are required ranging from hourly, multi-hourly, daily, multi-daily, weekly or monthly, or in some other suitable time interval. The treatment might comprise solely the application of the nucleic acid molecule or this may be applied in conjunction with other treatments for the skin proliferation and/or inflammatory disorder being treated or for other associated conditions including microbial infection, bleeding and the formation of a variety of rashes.
[0023] As an alternative to or in conjunction with antisense therapy, the subject invention extends to the nucleic acid molecule as, or incorporating, a ribozyme including a minizyme to, for example, IGF-I, its receptor or to molecules such as IGFBPs and in particular IGFBP-2 and -3. Ribozymes are synthetic nucleic acid molecules which possess highly specific endoribonuclease activity. In particular, they comprise a hybridising region which is complementary in nucleotide sequence to at least part of a target RNA. Ribozymes are well described by Haseloff and Gerlach (8) and in International Patent Application No. WO 89/05852. The present invention extends to ribozymes which target mRNA specified by genes encoding IGF-I, its receptor or one or more IGFBPs such as IGFBP-2 and/or IGFBP-3.
[0024] According to this embodiment, there is provided in a particularly preferred aspect a ribozyme comprising a hybridising region and a catalytic region wherein the hybridising region is capable of hybridising to at least part of a target mRNA sequence transcribed from a genomic gene corresponding to SEQ ID NO. 1 or SEQ ID NO. 2 wherein said catalytic domain is capable of cleaving said target mRNA sequence to reduce or inhibit IGF-I mediated cell proliferation and/or inflammation.
[0025] Yet another aspect of the present invention contemplates co-suppression to reduce expression or to inhibit translation of an endogenous gene encoding, for example, IGF-I, its receptor, or IGFBPs such as IGFBP-2 and/or -3. In co-suppression, a second copy of an endogenous gene or a substantially similar copy or analogue of an endogenous gene is introduced into a cell following topical administration. As with antisense molecules, nucleic acid molecules defining a ribozyme or nucleic acid molecules useful in co-suppression may first be protected such as by using a nonionic backbone.
[0026] The efficacy of the nucleic acid molecules of the present invention can be conveniently tested and screened using an in vitro system comprising a basal keratinocyte cell line. A particularly useful system comprises the HaCaT cell line described by Boukamp et al (9). In one assay, IGF-I is added to an oligonucleotide treated HaCaT cell line. Alternatively, growth of oligonucleotide treated HaCaT cells is observed on a feeder layer of irradiated 3T3 fibroblasts. Using such in vitro assays, it is observed that antisense oligonucleotides to IGFBP-3, for example, inhibit production of IGFBP-3 by HaCaT cells. Other suitable animal models include the nude mouse/human skin graft model (15; 16) and the “flaky skin” mouse model (17; 18). In the nude mouse model, microdermatome biopsies of psoriasis lesions are taken under local anaesthetic from volunteers then transplanted to congenital athymic (nude) mice. These transplanted human skin grafts maintain the characteristic hyperproliferating epidermis for 6-8 weeks. They are an established model for testing the efficacy of topically applied therapies for psoriasis. In the “flaky skin” mouse model, the fsn/fsn mutation produces mice with skin resembling human psoriasis. This mouse, or another mutant mouse with a similar phenotype is a further in vivo model to test the efficacy of topically applied therapies for psoriasis.
[0027] Another aspect of the present invention contemplates a pharmaceutical composition for topical administration which comprises a nucleic acid molecule capable of inhibiting or otherwise reducing IGF-I mediated cell proliferation such as psoriasis and one or more pharmaceutically acceptable carriers and/or diluents. Preferably, the nucleic acid molecule is an antisense molecule to IGF-I, the IGF-I receptor or an IGFBP such as IGFBP-2 and/or IGFBP-3 or comprises a ribozyme to one or more of these targets or is a molecule suitable for co-suppression of one or more of these targets. The composition may comprise a single species of a nuleic acid molecule capable of targeting one of IGF-I, its receptor or an IGFBP, such as IGFBP-2 or IGFBP-3 or may be a multi-valent molecule capable of targeting two or more of IGF-I, its receptor or an IGFBP, such as IGFBP-2 and/or IGFBP-3.
[0028] The nucleic acid molecules may be administered in dispersions prepared in creams, ointments, oil or other suitable carrier and/or diluent such as glycerol, liquid polyethylene glycols and/or mixtures thereof. Under ordinary conditions of storage and use, these preparations may contain a preservative to prevent the growth of microorganisms.
[0029] The pharmaceutical forms suitable for topical use include sterile aqueous solutions (where water soluble) or dispersions and powders for the extemporaneous preparation of topical solutions or dispersion. In all cases, the form is preferably sterile although this is not an absolute requirement and is stable under the conditions of manufacture and storage. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof and vegetable oils. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of superfactants. The prevention of the action of microorganism can be brought about by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thirmerosal and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars or sodium chloride.
[0030] Topical solutions arc prepared by incorporating the nucleic acid molecule compound in the required amount in the appropriate solvent with various of the other ingredients enumerated above, as required, followed by where necessary filter sterilization.
[0031] As used herein “pharmaceutically acceptable carriers and/or diluents” include any and all solvents, dispersion media, aqueous solutions, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like. The use of such media and agents for pharmaceutical active substances is well known in the art. Except insofar as any conventional media or agent is incompatable with the active ingredient, use thereof in the pharmaceutical compositions is contemplated. Supplementary active ingredients can also be incorporated into the compositions. Conveniently, the nucleic acid molecules of the present invention are stored in freeze-dried form and are reconstituted prior to use.
[0032] Yet another aspect of the present invention contemplates the use of a nucleic acid molecule in the manufacture of a medicament for the treatment of proliferative and/or inflammatory skin disorders mediated by a growth factor. The proliferative and/or inflammatory skin disorder is generally psoriasis and the nucleic acid molecule targets IGF-I, the IGF-I receptor and/or an IGFBP such as IGFBP-2 and/or IGFBP-3.
[0033] Still a further aspect of the present invention contemplates an agent comprising a nucleic acid molecule as hereinbefore defined useful in the treatment of proliferative and/or inflammatory skin disorders, such as psoriasis.
[0034] The present invention is further described by the following non-limiting Figures and/or Examples.
[0035] In the Figures:
[0036] FIG. 1 is a representation of the nucleotide sequence of IGFBP-2. 1 LOCUS HSIGFBP2 1433 bp RNA PRI 31-JAN-1990 DEFINITION Human mRNA for insulin-like growth factor binding protein (IGFBP-2) ACCESSION X16302 KEYWORDS insulin-like growth factor binding protein. SOURCE human ORGANISM Homo sapiens Eukaryota; Animalia; Metazoa; Chordata; Vertebrata; Mammalia; Theria; Eutheria; Primates; Haplorhini; Catarrhini; Hominidae. REFERENCE 1 (bases 1 to 1433) AUTHORS Binkert,C., Landwehr,J., Mary,J.L., Schwander,J. and Heinrich,G. TITLE Cloning, sequence analysis and expression of a cDNA encoding a novel insulin-like growth factor binding protein (IGFBP-2) JOURNAL EMBO J. 8, 2497-2502 (1989) STANDARD full automatic COMMENT NCBI gi: 33009 FEATURES Location/Qualifiers source 1. .1433 /organism=“Homo sapiens” /dev_stage=“fetal” /tissue_type=“liver” misc_feature 1416. .1420 /note=“pot. polyadenylation signal” polyA_site 1433 /note=“polyadenylation site” CDS 118. .1104 /note=“precursor polypeptide; (AA -39 to 289); NCBI gi: 33010.” /codon_start=1 /translation=“MLPRVGCPALPLPPPPLLPLLPLLLLLLGASGGGGGARAEVLFR CPPCTPERLAACGPPPVAPPAAVAAVAGGARMPCAELVREPGCGCCSVCARLEGEACG VYTPRCGQGLRCYPHPGSELPLQALVMGEGTCEKRRDAEYGASPEQVADNGDDHSEGG LVENHVDSTMNMLGGGGSAGRKPLKSGMKELAVFREKVTEQHRQMGKGGKHHLGLEEP KKLRPPPARTPCQQELDQVLERISTMRLPDERGPLEHLYSLHIPNCDKHGLYNLKQCK MSLNGQRGECWCVNPNTGKLIQGAPTIRGDPECHLFYNEQQEACGVHTQRMQ” CDS 118. .234 /note=“signal peptide; (AA -39 to -1); NCBI gi: 33011.” /codon_start=1 /translation=“MLPRVGCPALPLPPPPLLPLLPLLLLLLGASGGGGGARA” CDS 235. .1101 /note=“mature IGFBP-2; (AA 1 to 289); NCBI gi: 33012.” /codon_start=1 /translation=“EVLFRCPPCTPERLAACGPPPVAPPAAVAAVAGGARMPCAELVR EPGCGCCSVCARLEGEACGVYTPRCGQGLRCYPHPGSELPLQALVMGEGTCEKRRDAE YGASPEQVADNGDDHSEGGLVENHVDSTMNMLGGGGSAGRKPLKSGMKELAVFREKVT EQHRQMGKGGKHHKGLEEPKKLRPPPARTPCQQELDQVLERISTMRLPDERGPLEHLY SLHIPNCDKEGLYNLKQCKMSLNGQRGECWCVNPNTGKLIQGAPTIRGDPECHLFYNE QQEACGVHTQRMQ” BASE COUNT 239 a 466 c 501 g 227 t ORIGIN HSIGFBP2 Length: 1433 May 11, 1994 10:06 Type: N Check: 6232 ..
[0037] FIG. 2 is a representation of the nucleotide sequence of IGFBP-3. 2 LOCUS HUMGFIBPA 2474 bp ss-mRNA PRI 15-JUN-1990 DEFINITION Human growth hormone-dependent insulin-like growth factor-binding protein mRNA, complete cds. ACCESSION M31159 KEYWORDS insulin-like growth factor binding protein. SOURCE Human plasma, eDNA to mRNA, clone BP-53. ORGANISM Homo sapiens Eukaryota; Animalia; Chordata; Vertebrata; Mammalia; Theria; Eutheria; Primates; Haplorhini; Catarrhini; Hominidae. REFERENCE 1 (bases 1 to 2474) AUTHORS Wood,W.I., Cachianes,G., Henzel,W.J., Winslow,G.A., Spencer,S.A., Hellmiss,R., Martin,J.L. and Baxter,R.C. TITLE Cloning and expression of the growth hormone-dependent insulin-like growth factor-binding protein JOURNAL Mol. Endocrinol. 2, 1176-1185 (1988) STANDARD full automatic COMMENT NCBI gi: 183115 FEATURES Location/Qualifiers mRNA <1. .2474 /note=“GFIBP mRNA” CDS 110. .985 /gene=“IGFBP1” /note=“insulin-like growth factor-binding protein; NCBI gi: 183116.” /codon_start=1 /translation=“MQRARPTLWAAALTLLVLLRGPPVARAGASSGGLGPVVRCEPCD ARALAQCAPPPAVCAELVREPGCGCCLTCALSEGQPCGIYTERCGSGLRCQPSPDEAR PLQALLDGRGLCVNASAVSRLAYLLJPAPPAPGNASESEEDRSAGSVESPSVSSTHRV SDPKFWPLHSKIIIIKKGHAKDSQRYKDYESQSTDTQNFSSESKRETEYGPCRREME DTLNHLKFLNVLSPRGHIPNCDKKGFYKKKKQCRPSKGRKRGFCWCVCDKYGQPLPGYT TKGKEDVHCYSMQSK” source 1. .2474 /organism=“Homo sapiens” BASE COUNT 597 a 646 c 651 g 580 t ORIGIN HUMGFIBPA Length: 2474 May 11, 1994 10:00 Type: N Check: 9946 ..
[0038] FIG. 3 is a representation of the nucleotide sequence of IGF-l-receptor. 3 LOCUS HSIGFIRR 4989 bp RNA PRI 28-MAR-1991 DEFINITION Human mRNA for insulin-like growth factor I receptor ACCESSION X04434 M24599 KEYWORDS glycoprotein; insulin receptor; insulin-like growth factor I receptor; membrane glycoprotein; receptor; tyrosine kinase. SOURCE human ORGANISM Homo sapiens Eukaryota; Animalia; Metazoa; Chordata; Vertebrata; Mammalia; Theria; Eutheria; Primates; Haplorhini; Catarrhini; Hominidae. REFERENCE 1 (bases 1 to 4989) AUTHORS Ullrich,A., Gray,A., Tam,A.W., Yang-Feng,T., Tsubokawa,M., Collins,C., Henzel,W., Bon,T.L., Kathuria,S., Chen,E., Jakobs,S., Francke , U., Ramachandran, J. and Fujita-Yamaguchi, Y. TITLE Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural dererminants that define functional specificity JOURNAL EMBO J. 5, 2503-2512 (1986) STANDARD full automatic COMMENT NCBI gi: 33058 FEATURES Location/Qualifiers source 1. .4989 /organism=“Homo sapiens” /tissue_type=“placenta” /clone—lib=“ (lamda)gt10” /clone=“ (lambda) IGF-1-R.85, (lambda) IGF-1-R.76” sig_peptide 32. .121 mat_peptide 122. .4132 /note=“IGF-I receptor” misc_feature 122. .2251 /note=“alpha-subunit (AA 1 - 710)” misc_feature 182. .190 /note=“pot.N-linked glycosylation site (AA 21 - 23)” misc_feature 335. .343 /note=“pot.N-linked glycostlation site (AA 72 - 74)” misc_feature 434. .442 /note=“pot.N-linked glycostlation site (AA 105 - 107)” misc_feature 761. .769 /note=“pot.N-linked glycostlation site (AA 214 - 216)” misc_feature 971. .979 /note=“pot.N-linked glycostlation site (AA 284 - 286)” misc feature 1280. .1288 /note=“pot.N-linked glycostlation site (AA 387 - 389)” misc_feature 1343. .1351 /note=“pot.N-linked glycosylation site (AA 408 - 410)” misc_feature 1631. .1639 /note=“pot.N-linked glycostlation site (AA 504 - 506)” misc_feature 1850. .1858 /note=“pot.N-linked glycosylation site (AA 577 - 579)” misc feature 1895. .1903 /note.“pot.N-linked glycosylation site (AA 592 - 594)” misc_feature 1949. .1957 /note=“pot.N- linked glycosylation site (AA 610 - 612)” misc_feature 2240. .2251 /note=“putative proreceptor processing site (AA 707 - 710)” misc_feature 2252. .4132 /note=“beta-subunit (AA 711 - 1337)” misc_feature 2270. .2278 /note=“pot.N-linked glycosylation site (AA 717 - 719]” misc_feature 2297. .2305 /note=“pot.N-linked glycosylation site (AA 726 - 728)” misc feature 2321. .2329 /note=“pot.N-linked glycosylation site (AA 734 - 736)” misc_feature 2729. .2737 /note=“pot.N-linked glycosylation site (AA 870 - 872)” misc feature 2768. .2776 /note=“pot.N-linked glycosylation site (AA 883 - 885)” misc_feature 2837. .2908 /note=“transmembrane region (AA 906 - 929)” misc feature 2918. .2926 /note=“pot.N-linked glycosylation site (AA 933 - 935)” misc_feature 3047. .3049 /note=“pot.ATP binding site (AA 976)” misc feature 3053. .3055 /note=“pot.ATP binding site (AA 978)” misc feature 3062. .3064 /note=“pot.ATP binding site (AA 981)” misc_feature 3128. .3130 /note=“pot.ATP binding site (AA 1003)” CDS 32. .4132 /product=“IGF-I receptor” /note=“50 stops when translation attempted, frame 1, code 0” BASE COUNT 1216 a 1371 c 1320 g 1082 t ORIGIN HSIGFIRR Length: 4989 May 11, 1994 12:10 Type: N Check: 133 ..
[0039] FIG. 4A is a photographic representation of a Western ligand blot of HaCaT conditioned medium showing IGFBP-3 secreted in 24 hours after 7 day treatment with phosphorothioate oligonucleotides (BP3AS2, BP3AS3 and BP3S) at 0.5 &mgr;M and 5 &mgr;M; * no oligonucleotide added.
[0040] FIG. 4B is a graphical representation of a scanning imaging desitometry of Western ligand blot (FIG. 4A), showing relative band intensities of IGFBP-3 and the 24 kDa IGFBP-4 after treatment with phosphorothioate oligonucleotides; * no oligonucleotide added.
[0041] FIG. 5A is a photographic representation of a Western ligand blot of HaCaT conditioned medium showing IGFBP-3 secreted in 24 hours after 7 day treatment with phosophorothioate oligonucleotide BP3AS2 at 0.5 &mgr;M compared with several control oligonucleotides at 0.5 &mgr;M. (a) oligonucleotide BP3AS2NS; (b) oligonucleotide BP3AS4; (c) oligonucleotide BP3AS4NS; and (untreated), no oligonucleotide added.
[0042] FIG. 5B is a graphical representation of a scanning imaging densitometry of Western ligand blot (FIG. 5A), showing relative band intensities of IGFBP-3 after treatment with phosphorothioate oligonucleotides as in FIG. 5A, showing IGFBP-3 band intensities expressed as a percentage of the average band intensity from conditioned medium of cells not treated with oligonucleotide.
[0043] FIG. 6 is a graphical representation showing inhibition of IGF-I binding by antisense oligonucleotides to IGF-I receptor. IGFR.AS: antisense; IGFR.S: sense.
[0044] FIG. 7 is a graphical representation showing inhibition of IGFBP-3 production in culture medium following initial treatment with antisense oligonucleotides once daily over a 2 day period.
[0045] FIG. 8 is a graphical representation showing optimization of IGFBP-3 antisense oligonucleotide concentration as determined by relative IGFBP-3 concentration in culture medium.
EXAMPLE 1 In Vitro Assay[0046] Cells
[0047] The differentiated human keratinocyte cell line, HaCaT (9) was used in the in vitro assay. Cells at passage numbers 33 to 36 were maintained as monolayer cultures in 5% v/v CO2 at 37° C. in Keratinocyte-SFM (Gibco) containing EGF and bovine pituitary extract as supplied. Media containing foetal calf serum were avoided because of the high content of IGF-I binding proteins in serum.
[0048] Feeder layer plates of lethally irradiated 3T3 fibroblasts were prepared exactly as described by Rheinwald and Green (10).
EXAMPLE 2 In Vitro Assay[0049] Thymidine Incorporation Assay
[0050] Cells were grown to 4 days post confluence in 2 cm2 wells with daily medium changes of Keratinocyte-SFM, then the medium was changed to DMEM (Cytosystems, Australia), with the following additions: 25 mM Hepes, 0.19% w/v, sodium bicarbonate, 0.03% w/v glutamine (Sigma Chemical Co, USA), 50 IU/ml penicillin and 50 &mgr;g/ml streptomycin (Flow Laboratories). After 24 hours, IGF-I or tIGF-I was added to triplicate wells, at the concentrations indicated, in 0.5 ml fresh DMEM containing 0.02% v/v bovine serum albumin (Sigma molecular biology grade) and incubated for a further 21 hours. [3H]-Thymidine (0.1 &mgr;Ci/well) was then added and the cells incubated for a further 3 hours. The medium was then aspirated and the cells washed once with ice-cold PBS and twice with ice-cold 10% v/v TCA. The TCA-precipitated monolayers were then solubilized with 0.25M NaOH (200 &mgr;l/well), transferred to scintillation vials and radioactivity determined by liquid scintillation counting (Pharmacia Wallac 1410 liquid scintillation counter).
EXAMPLE 3 Western Ligand Blotting[0051] HaCaT conditioned medium (250 &mgr;l) was concentrated by adding 750 &mgr;l cold ethanol, incubating at −20° C. for 2 hours and centrifuging at 16,000 g for 20 min at 4° C. The resulting pellet was air dried, resuspended thoroughly in non-reducing Laemmli sample buffer, heated to 90° C. for 5 minutes and separated on 12% w/v SDS-PAGE according to the method of Laemmli (1970). Separated proteins were electrophoretically transferred to nitrocellulose membrane (0.45 mm, Schleicher and Schuell, Dassel, Germany) in a buffer containing 25 mM Tris, 192 mM glycine and 20% v/v methanol. IGFBPs were then visualised by the procedure of Hossenlopp et al (11), using [125I]-IGF-I, followed by autoradiography. Autoradiographs were scanned in a BioRad Model GS-670 Imaging Densitometer and band densities were determined using the Molecular Analyst program.
EXAMPLE 4 Antisense Oligonucleotides[0052] Phosphorothioate oligodeoxynucleotides were synthesised by Bresatec, Adelaide, South Australia, Australia. The following antisense sequences were used: BP3AS2, 5′-GCG CCC GCT GCA TGA CGC CTG CAA C-3′ (SEQ ID NO. 4), a 25mer complementary to the start codon region of the human IGFBP-3 mRNA; BP3AS3, 5′-CGG GCG GCT CAC CTG GAG CTG GCG-3′ (SEQ ID NO. 5), a 24 mer complementary to the exon 1/intron 1 splice site; BP3AS4, 5′-AGG CGG CTG ACG GCA CTA-3′ (SEQ ID NO. 6), an 18 mer complementary to a region of the coding sequence lacking RNA secondary structure and oligonucleotide-dimer formation (using the computer software “OLIGO for PC”). Since BP3AS4 was found to be ineffective at inhibiting IGFBP-3 synthesis, it was used as a control. The following additional control oligonucleotide sequences were used: BP3S, 5′-CAG GCG TCA TGC AGC GGG C-3′ (SEQ ID NO. 7), an 18 mer sense control sequence equivalent to the start codon region; BP3AS2NS, 5′-CGG AGA TGC CGC ATG CCA GCG CAG G-3′ (SEQ ID NO. 8), a 25 mer randomised sequence with the same GC content as BP3AS2; BP3AS4NS, 5′-GAC AGC GTC GGA GCG ATC-3′ (SEQ ID NO. 9), an 18 mer randomised sequence with the same GC content as BP3AS4NS. Design of the oligonucleotides was based on the human IGFBP-3 cDNA sequence of Spratt et al (12).
[0053] Cells were grown to one day post confluence in 2 cm2 wells with daily medium changes of 0.5 ml Keratinocyte-SFM, then subjected to daily medium changes of Keratinocyte-SFM for a further 4 days. Daily additions of 0.5 ml fresh Keratinocyte-SFM were then continued for a further 7 days, except that at the time of medium addition, 5 &mgr;l oligonucleotide in PBS was added to give the final concentrations indicated, then the wells were shaken to mix the oligonucleotide. After the final addition, cells were incubated for 24 hours and the medium collected for assay of IGFBPs. Cells were then counted after trypsinisation in a Coulter Industrial D Counter, Coulter Bedfordshire, UK. Cell numbers after oligonucleotide treatment differed by less than 10%.
EXAMPLE5 Antisense Oligonucleotides Inhibit IGFBP-3 Synthesis[0054] HaCaT cells secrete mainly IGFBP-3 (>95%), with the only other IGFBP detectable in HaCaT conditioned medium being IGFBP-4 (<5%). The effect on IGFBP-3 and IGFBP-4 synthesis of antisense oligonucleotides at two concentrations, 5 &mgr;M and 0.5 &mgr;M, was tested. Two oligonucleotides were used, BP3AS2 and BP3AS3, directed against the start site and the intron 1/exon 1 splice site, respectively of the IGFBP-3 mRNA. As a control, a sense oligonucleotide corresponding to the start site was used. As shown in FIGS. 4A and 4B, all oligonucleotides at 5 &mgr;M caused a significant reduction of IGFBP-3 synthesis compared with untreated cells, however, the two antisense oligonucleotides inhibited IGFBP-3 synthesis of approximately 50% compared to the sense control (FIG. 4B). The antisense oligonucleotide directed to the start codon appeared to be more effective of the two, the difference being more apparent at the lower concentration of 0.5 &mgr;M. The cells of IGFBP4 secreted by the HaCaT cells make photographic reproduction of the bands on Western ligand blots difficult, however densitometry measurements provide adequate relative quantitation. This resulted in the significant observation that IGFBP4 levels were unaffected by oligonucleotide addition to the cells, suggesting that the observed inhibitory effects on IGFBP-3 are specific.
[0055] To further investigate the inhibitory effects of the more effective of the two antisense oligonucleotides, BP3AS2, inhibition by this oligonucleotide at 0.5 &mgr;M was compared with a number of control oligonucleotides, including one antisense oligonucleotide to IGFBP-3 that had proved to be ineffective at 0.5 &mgr;M. As shown in FIGS. 5A and 5B, BP3AS2 was again inhibitory, resulting in levels of IGFBP-3 of approximately 50% of the most non-specifically inhibitory control oligonucleotide, the randomised equivalent of BP3AS2. The other control oligonucleotides caused no reduction in IGFBP-3 levels at 0.5 &mgr;M, compared to untreated cells. Of possible significance is the fact that this control oligonucleotide, BP3AS2NS, like BP3AS2 itself, has the highest potential Tm of the three control oligonucleotides used in this experiment, enhancing the probability of non-specific base pairing with ron-target mRNAs. However, the lack of inhibition of IGFBP4 secretion by BP3AS2 suggests that this oligonucleotide is selective even compared with the most closely related protein likely to be present in this cell line.
EXAMPLE 6 Antisense Oligonucleotides of IGFBP2[0056] Antisense oligonucleotides to IGFBP2 may be selected from molecules capable of interacting with one or more of the following sense oligonucleotides: 4 ATTCGGGGCGAGGGA AAGAAGCGGAGGAGG CCCGCTCGCAGGGCC TTCGGGGCGAGGGAG AGAAGCGGAGGAGGC CCGCTCGCAGGGCCG TCGGGGCGAGGGAGG GAAGCGGAGGAGGCG CGCTCGCAGGGCCGT CGGGGCGAGGGAGGA AAGCGGAGGAGGCGG GCTCGCAGGGCCGTG GGGGCGAGGGAGGAG AGCGGAGGAGGCGGC CTCGCAGGGCCGTGC GGGCGAGGGAGGAGG GCGGAGGAGGCGGCT TCGCAGGGCCGTGCA GGCGAGGGAGGAGGA CGGAGGAGGCGGCTC CGCAGGGCCGTGCAC GCGAGGGAGGAGGAA GGAGGAGGCGGCTCC GCAGGGCCGTGCACC CGAGGGAGGAGGAAG GAGGAGGCGGCTCCC CAGGGCCGTGCACCT GAGGGAGGAGGAAGA AGGAGGCGGCTCCCG AGGGCCGTGCACCTG AGGGAGGAGGAAGAA GGAGGCGGCTCCCGC GGGCCGTGCACCTGC GGGAGGAGGAAGAAG GAGGCGGCTCCCGCT GGCCGTGCACCTGCC GGAGGAGGAAGAAGC AGGCGGCTCCCGCTC GCCGTGCACCTGCCC GAGGAGGAAGAAGCG GGCGGCTCCCGCTCG CCGTGCACCTGCCCG AGGAGGAAGAAGCGG GCGGCTCCCGCTCGC CGTGCACCTGCCCGC GGAGGAAGAAGCGGA CGGCTCCCGCTCGCA GTGCACCTGCCCGCC GAGGAAGAAGCGGAG GGCTCCCGCTCGCAG TGCACCTGCCCGCCC AGGAAGAAGCGGAGG GCTCCCGCTCGCAGG GCACCTGCCCGCCCG GGAAGAAGCGGAGGA CTCCCGCTCGCAGGG CACCTGCCCGCCCGC GAAGAAGCGGAGGAG TCCCGCTCGCAGGGC ACCTGCCCGCCCGCC CCTGCCCGCCCGCCC CATGCTGCCGAGAGT CGCTGCTGCCGCTGC CTGCCCGCCCGCCCG ATGCTGCCGAGAGTG GCTGCTGCCGCTGCT TGCCCGCCCGCCCGC TGCTGCCGAGAGTGG CTGCTGCCGCTGCTG GCCCGCCCGCCCGCT GCTGCCGAGAGTGGG TGCTGCCGCTGCTGC CCCGCCCGCCCGCTC CTGCCGAGAGTGGGC GCTGCCGCTGCTGCT CCGCCCGCCCGCTCG TGCCGAGAGTGGGCT CTGCCGCTGCTGCTG CGCCCGCCCGCTCGC GCCGAGAGTGGGCTG TGCCGCTGCTGCTGC GCCCGCCCGCTCGCT CCGAGAGTGGGCTGC GCCGCTGCTGCTGCT CCCGCCCGCTCGCTC CGAGAGTGGGCTGCC CCGCTGCTGCTGCTG CCGCCCGCTCGCTCG GAGAGTGGGCTGCCC CGCTGCTGCTGCTGC CGCCCGCTCGCTCGC AGAGTGGGCTGCCCC GCTGCTGCTGCTGCT GCCCGCTCGCTCGCT GAGTGGGCTGCCCCG CTGCTGCTGCTGCTA CCCGCTCGCTCGCTC AGTGGGCTGCCCCGC TGCTGCTGCTGCTAC CCGCTCGCTCGCTCG GTGGGCTGCCCCGCG GCTGCTGCTGCTACT CGCTCGCTCGCTCGC TGGGCTGCCCCGCGC CTGCTGCTGCTACTG GCTCGCTCGCTCGCC GGGCTGCCCCGCGCT TGCTGCTGCTACTGG CTCGCTCGCTCGCCC GGCTGCCCCGCGCTG GCTGCTGCTACTGGG TCGCTCGCTCGCCCG GCTGCCCCGCGCTGC CTGCTGCTACTGGGC CGCTCGCTCGCCCGC CTGCCCCGCGCTGCC TGCTGCTACTGGGCG GCTCGCTCGCCCGCC TGCCCCGCGCTGCCG GCTGCTACTGGGCGC CTCGCTCGCCCGCCG GCCCCGCGCTGCCGC CTGCTACTGGGCGCG TCGCTCGCCCGCCGC CCCCGCGCTGCCGCT TGCTACTGGGCGCGA CGCTCGCCCGCCGCG CCCGCGCTGCCGCTG GCTACTGGGCGCGAG GCTCGCCCGCCGCGC CCGCGCTGCCGCTGC CTACTGGGCGCGAGT CTCGCCCGCCGCGCC CGCGCTGCCGCTGCC TACTGGGCGCGAGTG TCGCCCGCCGCGCCG GCGCTGCCGCTGCCG ACTGGGCGCGAGTGG CGCCCGCCGCGCCGC CGCTGCCGCTGCCGC CTGGGCGCGAGTGGC GCCCGCCGCGCCGCG GCTGCCGCTGCCGCC TGGGCGCGAGTGGCG CCCGCCGCGCCGCGC CTGCCGCTGCCGCCG GGGCGCGAGTGGCGG CCGCCGCGCCGCGCT TGCCGCTGCCGCCGC GGCGCGAGTGGCGGC CGCCGCGCCGCGCTG GCCGCTGCCGCCGCC GCGCGAGTGGCGGCG GCCGCGCCGCGCTGC CCGCTGCCGCCGCCG CGCGAGTGGCGGCGG CCGCGCCGCGCTGCC CGCTGCCGCCGCCGC GCGAGTGGCGGCGGC CGCGCCGCGCTGCCG GCTGCCGCCGCCGCC CGAGTGGCGGCGGCG GCGCCGCGCTGCCGA CTGCCGCCGCCGCCG GAGTGGCGGCGGCGG CGCCGCGCTGCCGAC TGCCGCCGCCGCCGC AGTGGCGGCGGCGGC GCCGCGCTGCCGACC GCCGCCGCCGCCGCT GTGGCGGCGGCGGCG CCGCGCTGCCGACCG CCGCCGCCGCCGCTG TGGCGGCGGCGGCGG CGCGCTGCCGACCGC CGCCGCCGCCGCTGC GGCGGCGGCGGCGGG GCGCTGCCGACCGCC GCCGCCGCCGCTGCT GCGGCGGCGGCGGGG CGCTGCCGACCGCCA CCGCCGCCGCTGCTG CGGCGGCGGCGGGGC GCTGCCGACCGCCAG CGCCGCCGCTGCTGC GGCGGCGGCGGGGCG CTGCCGACCGCCAGC GCCGCCGCTGCTGCC GCGGCGGCGGGGCGC TGCCGACCGCCAGCA CCGCCGCTGCTGCCG CGGCGGCGGGGCGCG GCCGACCGCCAGCAT CGCCGCTGCTGCCGC GGCGGCGGGGCGCGC CCGACCGCCAGCATG GCCGCTGCTGCCGCT GCGGCGGGGCGCGCG CGACCGCCAGCATGC CCGCTGCTGCCGCTG CGGCGGGGCGCGCGC GACCGCCAGCATGCT CGCTGCTGCCGCTGC GGCGGGGCGCGCGCG ACCGCCAGCATGCTG GCTGCTGCCGCTGCT GCGGGGCGCGCGCGG CCGCCAGCATGCTGC CTGCTGCCGCTGCTG CGGGGCGCGCGCGGA CGCCAGCATGCTGCC TGCTGCCGCTGCTGC GGGGCGCGCGCGGAG GCCAGCATGCTGCCG GCTGCCGCTGCTGCC GGGCGCGCGCGGAGG CCAGCATGCTGCCGA CTGCCGCTGCTGCCG GGCGCGCGCGGAGGT CAGCATGCTGCCGAG TGCCGCTGCTGCCGC GCGCGCGCGGAGGTG AGCATGCTGCCGAGA GCCGCTGCTGCCGCT CGCGCGCGGAGGTGC GCATGCTGCCGAGAG CCGCTGCTGCCGCTG GCGCGCGGAGGTGCT CGCGCGGAGGTGCTG CGGGCCCCCGCCGGT GCATGCCATGCGCGG GCGCGGAGGTGCTGT GGGCCCCCGCCGGTT CATGCCATGCGCGGA CGCGGAGGTGCTGTT GGCCCCCGCCGGTTG ATGCCATGCGCGGAG GCGGAGGTGCTGTTC GCCCCCGCCGGTTGC TGCCATGCGCGGAGC CGGAGGTGCTGTTCC CCCCCGCCGGTTGCG GCCATGCGCGGAGCT GGAGGTGCTGTTCCG CCCCGCCGGTTGCGC CCATGCGCGGAGCTC GAGGTGCTGTTCCGC CCCGCCGGTTGCGCC CATGCGCGGAGCTCG AGGTGCTGTTCCGCT CCGCCGGTTGCGCCG ATGCGCGGAGCTCGT GGTGCTGTTCCGCTG CGCCGGTTGCGCCGC TGCGCGGAGCTCGTC GTGCTGTTCCGCTGC GCCGGTTGCGCCGCC GCGCGGAGCTCGTCC TGCTGTTCCGCTGCC CCGGTTGCGCCGCCC CGCGGAGCTCGTCCG GCTGTTCCGCTGCCC CGGTTGCGCCGCCCG GCGGAGCTCGTCCGG CTGTTCCGCTGCCCG GGTTGCGCCGCCCGC CGGAGCTCGTCCGGG TGTTCCGCTGCCCGC GTTGCGCCGCCCGCC GGAGCTCGTCCGGGA GTTCCGCTGCCCGCC TTGCGCCGCCCGCCG GAGCTCGTCCGGGAG TTCCGCTGCCCGCCC TGCGCCGCCCGCCGC AGCTCGTCCGGGAGC TCCGCTGCCCGCCCT GCGCCGCCCGCCGCG GCTCGTCCGGGAGCC CCGCTGCCCGCCCTG CGCCGCCCGCCGCGG CTCGTCCGGGAGCCG CGCTGCCCGCCCTGC GCCGCCCGCCGCGGT TCGTCCGGGAGCCGG GCTGCCCGCCCTGCA CCGCCCGCCGCGGTG CGTCCGGGAGCCGGG CTGCCCGCCCTGCAC CGCCCGCCGCGGTGG GTCCGGGAGCCGGGC TGCCCGCCCTGCACA GCCCGCCGCGGTGGC TCCGGGAGCCGGGCT GCCCGCCCTGCACAC CCCGCCGCGGTGGCC CCGGGAGCCGGGCTG CCCGCCCTGCACACC CCGCCGCGGTGGCCG CGGGAGCCGGGCTGC CCGCCCTGCACACCC CGCCGCGGTGGCCGC GGGAGCCGGGCTGCG CGCCCTGCACACCCG GCCGCGGTGGCCGCA GGAGCCGGGCTGCGG GCCCTGCACACCCGA CCGCGGTGGCCGCAG GAGCCGGGCTGCGGC CCCTGCACACCCGAG CGCGGTGGCCGCAGT AGCCGGGCTGCGGCT CCTGCACACCCGAGC GCGGTGGCCGCAGTG GCCGGGCTGCGGCTG CTGCACACCCGAGCG CGGTGGCCGCAGTGG CCGGGCTGCGGCTGC TGCACACCCGAGCGC GGTGGCCGCAGTGGC CGGGCTGCGGCTGCT GCACACCCGAGCGCC GTGGCCGCAGTGGCC GGGCTGCGGCTGCTG CACACCCGAGCGCCT TGGCCGCAGTGGCCG GGCTGCGGCTGCTGC ACACCCGAGCGCCTG GGCCGCAGTGGCCGG GCTGCGGCTGCTGCT CACCCGAGCGCCTGG GCCGCAGTGGCCGGA CTGCGGCTGCTGCTC ACCCGAGCGCCTGGC CCGCAGTGGCCGGAG TGCGGCTGCTGCTCG CCCGAGCGCCTGGCC CGCAGTGGCCGGAGG GCGGCTGCTGCTCGG CCGAGCGCCTGGCCG GCAGTGGCCGGAGGC CGGCTGCTGCTCGGT CGAGCGCCTGGCCGC CAGTGGCCGGAGGCG GGCTGCTGCTCGGTG GAGCGCCTGGCCGCC AGTGGCCGGAGGCGC GCTGCTGCTCGGTGT AGCGCCTGGCCGCCT GTGGCCGGAGGCGCC CTGCTGCTCGGTGTG GCGCCTGGCCGCCTG TGGCCGGAGGCGCCC TGCTGCTCGGTGTGC CGCCTGGCCGCCTGC GGCCGGAGGCGCCCG GCTGCTCGGTGTGCG GCCTGGCCGCCTGCG GCCGGAGGCGCCCGC CTGCTCGGTGTGCGC CCTGGCCGCCTGCGG CCGGAGGCGCCCGCA TGCTCGGTGTGCGCC CTGGCCGCCTGCGGG CGGAGGCGCCCGCAT GCTCGGTGTGCGCCC TGGCCGCCTGCGGGC GGAGGCGCCCGCATG CTCGGTGTGCGCCCG GGCCGCCTGCGGGCC GAGGCGCCCGCATGC TCGGTGTGCGCCCGG GCCGCCTGCGGGCCC AGGCGCCCGCATGCC CGGTGTGCGCCCGGC CCGCCTGCGGGCCCC GGCGCCCGCATGCCA GGTGTGCGCCCGGCT CGCCTGCGGGCCCCC GCGCCCGCATGCCAT GTGTGCGCCCGGCTG GCCTGCGGGCCCCCG CGCCCGCATGCCATG TGTGCGCCCGGCTGG CCTGCGGGCCCCCGC GCCCGCATGCCATGC GTGCGCCCGGCTGGA CTGCGGGCCCCCGCC CCCGCATGCCATGCG TGCGCCCGGCTGGAG TGCGGGCCCCCGCCG CCGCATGCCATGCGC GCGCCCGGCTGGAGG GCGGGCCCCCGCCGG CGCATGCCATGCGCG CGCCCGGCTGGAGGG GCCCGGCTGGAGGGC GCGCTGCTATCCCCA AGGGCACTTGTGAGA CCCGGCTGGAGGGCG CGCTGCTATCCCCAC GGGCACTTGTGAGAA CCGGCTGGAGGGCGA GCTGCTATCCCCACC GGCACTTGTGAGAAG CGGCTGGAGGGCGAG CTGCTATCCCCACCC GCACTTGTGAGAAGC GGCTGGAGGGCGAGG TGCTATCCCCACCCG CACTTGTGAGAAGCG GCTGGAGGGCGAGGC GCTATCCCCACCCGG ACTTGTGAGAAGCGC CTGGAGGGCGAGGCG CTATCCCCACCCGGG CTTGTGAGAAGCGCC TGGAGGGCGAGGCGT TATCCCCACCCGGGC TTGTGAGAAGCGCCG GGAGGGCGAGGCGTG ATCCCCACCCGGGCT TGTGAGAAGCGCCGG GAGGGCGAGGCGTGC TCCCCACCCGGGCTC GTGAGAAGCGCCGGG AGGGCGAGGCGTGCG CCCCACCCGGGCTCC TGAGAAGCGCCGGGA GGGCGAGGCGTGCGG CCCACCCGGGCTCCG GAGAAGCGCCGGGAC GGCGAGGCGTGCGGC CCACCCGGGCTCCGA AGAAGCGCCGGGACG GCGAGGCGTGCGGCG CACCCGGGCTCCGAG GAAGCGCCGGGACGC CGAGGCGTGCGGCGT ACCCGGGCTCCGAGC AAGCGCCGGGACGCC GAGGCGTGCGGCGTC CCCGGGCTCCGAGCT AGCGCCGGGACGCCG AGGCGTGCGGCGTCT CCGGGCTCCGAGCTG GCGCCGGGACGCCGA GGCGTGCGGCGTCTA CGGGCTCCGAGCTGC CGCCGGGACGCCGAG GCGTGCGGCGTCTAC GGGCTCCGAGCTGCC GCCGGGACGCCGAGT CGTGCGGCGTCTACA GGCTCCGAGCTGCCC CCGGGACGCCGAGTA GTGCGGCGTCTACAC GCTCCGAGCTGCCCC CGGGACGCCGAGTAT TGCGGCGTCTACACC CTCCGAGCTGCCCCT GGGACGCCGAGTATG GCGGCGTCTACACCC TCCGAGCTGCCCCTG GGACGCCGAGTATGG CGGCGTCTACACCCC CCGAGCTGCCCCTGC GACGCCGAGTATGGC GGCGTCTACACCCCG CGAGCTGCCCCTGCA ACGCCGAGTATGGCG GCGTCTACACCCCGC GAGCTGCCCCTGCAG CGCCGAGTATGGCGC CGTCTACACCCCGCG AGCTGCCCCTGCAGG GCCGAGTATGGCGCC GTCTACACCCCGCGC GCTGCCCCTGCAGGC CCGAGTATGGCGCCA TCTACACCCCGCGCT CTGCCCCTGCAGGCG CGAGTATGGCGCCAG CTACACCCCGCGCTG TGCCCCTGCAGGCGC GAGTATGGCGCCAGC TACACCCCGCGCTGC GCCCCTGCAGGCGCT AGTATGGCGCCAGCC ACACCCCGCGCTGCG CCCCTGCAGGCGCTG GTATGGCGCCAGCCC CACCCCGCGCTGCGG CCCTGCAGGCGCTGG TATGGCGCCAGCCCG ACCCCGCGCTGCGGC CCTGCAGGCGCTGGT ATGGCGCCAGCCCGG CCCCGCGCTGCGGCC CTGCAGGCGCTGGTC TGGCGCCAGCCCGGA CCCGCGCTGCGGCCA TGCAGGCGCTGGTCA GGCGCCAGCCCGGAG CCGCGCTGCGGCCAG GCAGGCGCTGGTCAT GCGCCAGCCCGGAGC CGCGCTGCGGCCAGG CAGGCGCTGGTCATG CGCCAGCCCGGAGCA GCGCTGCGGCCAGGG AGGCGCTGGTCATGG GCCAGCCCGGAGCAG CGCTGCGGCCAGGGG GGCGCTGGTCATGGG CCAGCCCGGAGCAGG GCTGCGGCCAGGGGC GCGCTGGTCATGGGC CAGCCCGGAGCAGGT CTGCGGCCAGGGGCT CGCTGGTCATGGGCG AGCCCGGAGCAGGTT TGCGGCCAGGGGCTG GCTGGTCATGGGCGA GCCCGGAGCAGGTTG GCGGCCAGGGGCTGC CTGGTCATGGGCGAG CCCGGAGCAGGTTGC CGGCCAGGGGCTGCG TGGTCATGGGCGAGG CCGGAGCAGGTTGCA GGCCAGGGGCTGCGC GGTCATGGGCGAGGG CGGAGCAGGTTGCAG GCCAGGGGCTGCGCT GTCATGGGCGAGGGC GGAGCAGGTTGCAGA CCAGGGGCTGCGCTG TCATGGGCGAGGGCA GAGCAGGTTGCAGAC CAGGGGCTGCGCTGC CATGGGCGAGGGCAC AGCAGGTTGCAGACA AGGGGCTGCGCTGCT ATGGGCGAGGGCACT GCAGGTTGCAGACAA GGGGCTGCGCTGCTA TGGGCGAGGGCACTT CAGGTTGCAGACAAT GGGCTGCGCTGCTAT GGGCGAGGGCACTTG AGGTTGCAGACAATG GGCTGCGCTGCTATC GGCGAGGGCACTTGT GGTTGCAGACAATGG GCTGCGCTGCTATCC GCGAGGGCACTTGTG GTTGCAGACAATGGC CTGCGCTGCTATCCC CGAGGGCACTTGTGA TTGCAGACAATGGCG TGCGCTGCTATCCCC GAGGGCACTTGTGAG TGCAGACAATGGCGA GCAGACAATGGCGAT CACCATGAACATGTT GTATGAAGGAGCTGG CAGACAATGGCGATG ACCATGAACATGTTG TATGAAGGAGCTGGC AGACAATGGCGATGA CCATGAACATGTTGG ATGAAGGAGCTGGCC GACAATGGCGATGAC CATGAACATGTTGGG TGAAGGAGCTGGCCG ACAATGGCGATGACC ATGAACATGTTGGGC GAAGGAGCTGGCCGT CAATGGCGATGACCA TGAACATGTTGGGCG AAGGAGCTGGCCGTG AATGGCGATGACCAC GAACATGTTGGGCGG AGGAGCTGGCCGTGT ATGGCGATGACCACT AACATGTTGGGCGGG GGAGCTGGCCGTGTT TGGCGATGACCACTC ACATGTTGGGCGGGG GAGCTGGCCGTGTTC GGCGATGACCACTCA CATGTTGGGCGGGGG AGCTGGCCGTGTTCC GCGATGACCACTCAG ATGTTGGGCGGGGGA GCTGGCCGTGTTCCG CGATGACCACTCAGA TGTTGGGCGGGGGAG CTGGCCGTGTTCCGG GATGACCACTCAGAA GTTGGGCGGGGGAGG TGGCCGTGTTCCGGG ATGACCACTCAGAAG TTGGGCGGGGGAGGC GGCCGTGTTCCGGGA TGACCACTCAGAAGG TGGGCGGGGGAGGCA GCCGTGTTCCGGGAG GACCACTCAGAAGGA GGGCGGGGGAGGCAG CCGTGTTCCGGGAGA ACCACTCAGAAGGAG GGCGGGGGAGGCAGT CGTGTTCCGGGAGAA CCACTCAGAAGGAGG GCGGGGGAGGCAGTG GTGTTCCGGGAGAAG CACTCAGAAGGAGGC CGGGGGAGGCAGTGC TGTTCCGGGAGAAGG ACTCAGAAGGAGGCC GGGGGAGGCAGTGCT GTTCCGGGAGAAGGT CTCAGAAGGAGGCCT GGGGAGGCAGTGCTG TTCCGGGAGAAGGTC TCAGAAGGAGGCCTG GGGAGGCAGTGCTGG TCCGGGAGAAGGTCA CAGAAGGAGGCCTGG GGAGGCAGTGCTGGC CCGGGAGAAGGTCAC AGAAGGAGGCCTGGT GAGGCAGTGCTGGCC CGGGAGAAGGTCACT GAAGGAGGCCTGGTG AGGCAGTGCTGGCCG GGGAGAAGGTCACTG AAGGAGGCCTGGTGG GGCAGTGCTGGCCGG GGAGAAGGTCACTGA AGGAGGCCTGGTGGA GCAGTGCTGGCCGGA GAGAAGGTCACTGAG GGAGGCCTGGTGGAG CAGTGCTGGCCGGAA AGAAGGTCACTGAGC GAGGCCTGGTGGAGA AGTGCTGGCCGGAAG GAAGGTCACTGAGCA AGGCCTGGTGGAGAA GTGCTGGCCGGAAGC AAGGTCACTGAGCAG GGCCTGGTGGAGAAC TGCTGGCCGGAAGCC AGGTCACTGAGCAGC GCCTGGTGGAGAACC GCTGGCCGGAAGCCC GGTCACTGAGCAGCA CCTGGTGGAGAACCA CTGGCCGGAAGCCCC GTCACTGAGCAGCAC CTGGTGGAGAACCAC TGGCCGGAAGCCCCT TCACTGAGCAGCACC TGGTGGAGAACCACG GGCCGGAAGCCCCTC CACTGAGCAGCACCG GGTGGAGAACCACGT GCCGGAAGCCCCTCA ACTGAGCAGCACCGG GTGGAGAACCACGTG CCGGAAGCCCCTCAA CTGAGCAGCACCGGC TGGAGAACCACGTGG CGGAAGCCCCTCAAG TGAGCAGCACCGGCA GGAGAACCACGTGGA GGAAGCCCCTCAAGT GAGCAGCACCGGCAG GAGAACCACGTGGAC GAAGCCCCTCAAGTC AGCAGCACCGGCAGA AGAACCACGTGGACA AAGCCCCTCAAGTCG GCAGCACCGGCAGAT GAACCACGTGGACAG AGCCCCTCAAGTCGG CAGCACCGGCAGATG AACCACGTGGACAGC GCCCCTCAAGTCGGG AGCACCGGCAGATGG ACCACGTGGACAGCA CCCCTCAAGTCGGGT GCACCGGCAGATGGG CCACGTGGACAGCAC CCCTCAAGTCGGGTA CACCGGCAGATGGGC CACGTGGACAGCACC CCTCAAGTCGGGTAT ACCGGCAGATGGGCA ACGTGGACAGCACCA CTCAAGTCGGGTATG CCGGCAGATGGGCAA CGTGGACAGCACCAT TCAAGTCGGGTATGA CGGCAGATGGGCAAG GTGGACAGCACCATG CAAGTCGGGTATGAA GGCAGATGGGCAAGG TGGACAGCACCATGA AAGTCGGGTATGAAG GCAGATGGGCAAGGG GGACAGCACCATGAA AGTCGGGTATGAAGG CAGATGGGCAAGGGT GACAGCACCATGAAC GTCGGGTATGAAGGA AGATGGGCAAGGGTG ACAGCACCATGAACA TCGGGTATGAAGGAG GATGGGCAAGGGTGG CAGCACCATGAACAT CGGGTATGAAGGAGC ATGGGCAAGGGTGGC AGCACCATGAACATG GGGTATGAAGGAGCT TGGGCAAGGGTGGCA GCACCATGAACATGT GGTATGAAGGAGCTG GGGCAAGGGTGGCAA GGCAAGGGTGGCAAG CCCTGCCAGGACTCC CCATGCGCCTTCCGG GCAAGGGTGGCAAGC CCTGCCAGGACTCCC CATGCGCCTTCCGGA CAAGGGTGGCAAGCA CTGCCAGGACTCCCT ATGCGCCTTCCGGAT AAGGGTGGCAAGCAT TGCCAGGACTCCCTG TGCGCCTTCCGGATG AGGGTGGCAAGCATC GCCAGGACTCCCTGC GCGCCTTCCGGATGA GGGTGGCAAGCATCA CCAGGACTCCCTGCC CGCCTTCCGGATGAG GGTGGCAAGCATCAC CAGGACTCCCTGCCA GCCTTCCGGATGAGC GTGGCAAGCATCACC AGGACTCCCTGCCAA CCTTCCGGATGAGCG TGGCAAGCATCACCT GGACTCCCTGCCAAC CTTCCGGATGAGCGG GGCAAGCATCACCTT GACTCCCTGCCAACA TTCCGGATGAGCGGG GCAAGCATCACCTTG ACTCCCTGCCAACAG TCCGGATGAGCGGGG CAAGCATCACCTTGG CTCCCTGCCAACAGG CCGGATGAGCGGGGC AAGCATCACCTTGGC TCCCTGCCAACAGGA CGGATGAGCGGGGCC AGCATCACCTTGGCC CCCTGCCAACAGGAA GGATGAGCGGGGCCC GCATCACCTTGGCCT CCTGCCAACAGGAAC GATGAGCGGGGCCCT CATCACCTTGGCCTG CTGCCAACAGGAACT ATGAGCGGGGCCCTC ATCACCTTGGCCTGG TGCCAACAGGAACTG TGAGCGGGGCCCTCT TCACCTTGGCCTGGA GCCAACAGGAACTGG GAGCGGGGCCCTCTG CACCTTGGCCTGGAG CCAACAGGAACTGGA AGCGGGGCCCTCTGG ACCTTGGCCTGGAGG CAACAGGAACTGGAC GCGGGGCCCTCTGGA CCTTGGCCTGGAGGA AACAGGAACTGGACC CGGGGCCCTCTGGAG CTTGGCCTGGAGGAG ACAGGAACTGGACCA GGGGCCCTCTGGAGC TTGGCCTGGAGGAGC CAGGAACTGGACCAG GGGCCCTCTGGAGCA TGGCCTGGAGGAGCC AGGAACTGGACCAGG GGCCCTCTGGAGCAC GGCCTGGAGGAGCCC GGAACTGGACCAGGT GCCCTCTGGAGCACC GCCTGGAGGAGCCCA GAACTGGACCAGGTC CCCTCTGGAGCACCT CCTGGAGGAGCCCAA AACTGGACCAGGTCC CCTCTGGAGCACCTC CTGGAGGAGCCCAAG ACTGGACCAGGTCCT CTCTGGAGCACCTCT TGGAGGAGCCCAAGA CTGGACCAGGTCCTG TCTGGAGCACCTCTA GGAGGAGCCCAAGAA TGGACCAGGTCCTGG CTGGAGCACCTCTAC GAGGAGCCCAAGAAG GGACCAGGTCCTGGA TGGAGCACCTCTACT AGGAGCCCAAGAAGC GACCAGGTCCTGGAG GGAGCACCTCTACTC GGAGCCCAAGAAGCT ACCAGGTCCTGGAGC GAGCACCTCTACTCC GAGCCCAAGAAGCTG CCAGGTCCTGGAGCG AGCACCTCTACTCCC AGCCCAAGAAGCTGC CAGGTCCTGGAGCGG GCACCTCTACTCCCT GCCCAAGAAGCTGCG AGGTCCTGGAGCGGA CACCTCTACTCCCTG CCCAAGAAGCTGCGA GGTCCTGGAGCGGAT ACCTCTACTCCCTGC CCAAGAAGCTGCGAC GTCCTGGAGCGGATC CCTCTACTCCCTGCA CAAGAAGCTGCGACC TCCTGGAGCGGATCT CTCTACTCCCTGCAC AAGAAGCTGCGACCA CCTGGAGCGGATCTC TCTACTCCCTGCACA AGAAGCTGCGACCAC CTGGAGCGGATCTCC CTACTCCCTGCACAT GAAGCTGCGACCACC TGGAGCGGATCTCCA TACTCCCTGCACATC AAGCTGCGACCACCC GGAGCGGATCTCCAC ACTCCCTGCACATCC AGCTGCGACCACCCC GAGCGGATCTCCACC CTCCCTGCACATCCC GCTGCGACCACCCCC AGCGGATCTCCACCA TCCCTGCACATCCCC CTGCGACCACCCCCT GCGGATCTCCACCAT CCCTGCACATCCCCA TGCGACCACCCCCTG CGGATCTCCACCATG CCTGCACATCCCCAA GCGACCACCCCCTGC GGATCTCCACCATGC CTGCACATCCCCAAC CGACCACCCCCTGCC GATCTCCACCATGCG TGCACATCCCCAACT GACCACCCCCTGCCA ATCTCCACCATGCGC GCACATCCCCAACTG ACCACCCCCTGCCAG TCTCCACCATGCGCC CACATCCCCAACTGT CCACCCCCTGCCAGG CTCCACCATGCGCCT ACATCCCCAACTGTG CACCCCCTGCCAGGA TCCACCATGCGCCTT CATCCCCAACTGTGA ACCCCCTGCCAGGAC CCACCATGCGCCTTC ATCCCCAACTGTGAC CCCCCTGCCAGGACT CACCATGCGCCTTCC TCCCCAACTGTGACA CCCCTGCCAGGACTC ACCATGCGCCTTCCG CCCCAACTGTGACAA CCCAACTGTGACAAG CGGGCAGCGTGGGGA GAGCCCCCACCATCC CCAACTGTGACAAGC GGGCAGCGTGGGGAG AGCCCCCACCATCCG CAACTGTGACAAGCA GGCAGCGTGGGGAGT GCCCCCACCATCCGG AACTGTGACAAGCAT GCAGCGTGGGGAGTG CCCCCACCATCCGGG ACTGTGACAAGCATG CAGCGTGGGGAGTGC CCCCACCATCCGGGG CTGTGACAAGCATGG AGCGTGGGGAGTGCT CCCACCATCCGGGGG TGTGACAAGCATGGC GCGTGGGGAGTGCTG CCACCATCCGGGGGG GTGACAAGCATGGCC CGTGGGGAGTGCTGG CACCATCCGGGGGGA TGACAAGCATGGCCT GTGGGGAGTGCTGGT ACCATCCGGGGGGAC GACAAGCATGGCCTG TGGGGAGTGCTGGTG CCATCCGGGGGGACC ACAAGCATGGCCTGT GGGGAGTGCTGGTGT CATCCGGGGGGACCC CAAGCATGGCCTGTA GGGAGTGCTGGTGTG ATCCGGGGGGACCCC AAGCATGGCCTGTAC GGAGTGCTGGTGTGT TCCGGGGGGACCCCG AGCATGGCCTGTACA GAGTGCTGGTGTGTG CCGGGGGGACCCCGA GCATGGCCTGTACAA AGTGCTGGTGTGTGA CGGGGGGACCCCGAG CATGGCCTGTACAAC GTGCTGGTGTGTGAA GGGGGGACCCCGAGT ATGGCCTGTACAACC TGCTGGTGTGTGAAC GGGGGACCCCGAGTG TGGCCTGTACAACCT GCTGGTGTGTGAACC GGGGACCCCGAGTGT GGCCTGTACAACCTC CTGGTGTGTGAACCC GGGACCCCGAGTGTC GCCTGTACAACCTCA TGGTGTGTGAACCCC GGACCCCGAGTGTCA CCTGTACAACCTCAA GGTGTGTGAACCCCA GACCCCGAGTGTCAT CTGTACAACCTCAAA GTGTGTGAACCCCAA ACCCCGAGTGTCATC TGTACAACCTCAAAC TGTGTGAACCCCAAC CCCCGAGTGTCATCT GTACAACCTCAAACA GTGTGAACCCCAACA CCCGAGTGTCATCTC TACAACCTCAAACAG TGTGAACCCCAACAC CCGAGTGTCATCTCT ACAACCTCAAACAGT GTGAACCCCAACACC CGAGTGTCATCTCTT CAACCTCAAACAGTG TGAACCCCAACACCG GAGTGTCATCTCTTC AACCTCAAACAGTGC GAACCCCAACACCGG AGTGTCATCTCTTCT ACCTCAAACAGTGCA AACCCCAACACCGGG GTGTCATCTCTTCTA CCTCAAACAGTGCAA ACCCCAACACCGGGA TGTCATCTCTTCTAC CTCAAACAGTGCAAG CCCCAACACCGGGAA GTCATCTCTTCTACA TCAAACAGTGCAAGA CCCAACACCGGGAAG TCATCTCTTCTACAA CAAACAGTGCAAGAT CCAACACCGGGAAGC CATCTCTTCTACAAT AAACAGTGCAAGATG CAACACCGGGAAGCT ATCTCTTCTACAATG AACAGTGCAAGATGT AACACCGGGAAGCTG TCTCTTCTACAATGA ACAGTGCAAGATGTC ACACCGGGAAGCTGA CTCTTCTACAATGAG CAGTGCAAGATGTCT CACCGGGAAGCTGAT TCTTCTACAATGAGC AGTGCAAGATGTCTC ACCGGGAAGCTGATC CTTCTACAATGAGCA GTGCAAGATGTCTCT CCGGGAAGCTGATCC TTCTACAATGAGCAG TGCAAGATGTCTCTG CGGGAAGCTGATCCA TCTACAATGAGCAGC GCAAGATGTCTCTGA GGGAAGCTGATCCAG CTACAATGAGCAGCA CAAGATGTCTCTGAA GGAAGCTGATCCAGG TACAATGAGCAGCAG AAGATGTCTCTGAAC GAAGCTGATCCAGGG ACAATGAGCAGCAGG AGATGTCTCTGAACG AAGCTGATCCAGGGA CAATGAGCAGCAGGA GATGTCTCTGAACGG AGCTGATCCAGGGAG AATGAGCAGCAGGAG ATGTCTCTGAACGGG GCTGATCCAGGGAGC ATGAGCAGCAGGAGG TGTCTCTGAACGGGC CTGATCCAGGGAGCC TGAGCAGCAGGAGGC GTCTCTGAACGGGCA TGATCCAGGGAGCCC GAGCAGCAGGAGGCT TCTCTGAACGGGCAG GATCCAGGGAGCCCC AGCAGCAGGAGGCTT CTCTGAACGGGCAGC ATCCAGGGAGCCCCC GCAGCAGGAGGCTTG TCTGAACGGGCAGCG TCCAGGGAGCCCCCA CAGCAGGAGGCTTGC CTGAACGGGCAGCGT CCAGGGAGCCCCCAC AGCAGGAGGCTTGCG TGAACGGGCAGCGTG CAGGGAGCCCCCACC GCAGGAGGCTTGCGG GAACGGGCAGCGTGG AGGGAGCCCCCACCA CAGGAGGCTTGCGGG AACGGGCAGCGTGGG GGGAGCCCCCACCAT AGGAGGCTTGCGGGG ACGGGCAGCGTGGGG GGAGCCCCCACCATC GGAGGCTTGCGGGGT GAGGCTTGCGGGGTG GGCGCCCCTGCCCCC GTGGTGGGTGCTGGA AGGCTTGCGGGGTGC GCGCCCCTGCCCCCC TGGTGGGTGCTGGAG GGCTTGCGGGGTGCA CGCCCCTGCCCCCCG GGTGGGTGCTGGAGG GCTTGCGGGGTGCAC GCCCCTGCCCCCCGC GTGGGTGCTGGAGGA CTTGCGGGGTGCACA CCCCTGCCCCCCGCC TGGGTGCTGGAGGAT TTGCGGGGTGCACAC CCCTGCCCCCCGCCC GGGTGCTGGAGGATT TGCGGGGTGCACACC CCTGCCCCCCGCCCC GGTGCTGGAGGATTT GCGGGGTGCACACCC CTGCCCCCCGCCCCT GTGCTGGAGGATTTT CGGGGTGCACACCCA TGCCCCCCGCCCCTC TGCTGGAGGATTTTC GGGGTGCACACCCAG GCCCCCCGCCCCTCT GCTGGAGGATTTTCC GGGTGCACACCCAGC CCCCCCGCCCCTCTC CTGGAGGATTTTCCA GGTGCACACCCAGCG CCCCCGCCCCTCTCC TGGAGGATTTTCCAG GTGCACACCCAGCGG CCCCGCCCCTCTCCA GGAGGATTTTCCAGT TGCACACCCAGCGGA CCCGCCCCTCTCCAA GAGGATTTTCCAGTT GCACACCCAGCGGAT CCGCCCCTCTCCAAA AGGATTTTCCAGTTC CACACCCAGCGGATG CGCCCCTCTCCAAAC GGATTTTCCAGTTCT ACACCCAGCGGATGC GCCCCTCTCCAAACA GATTTTCCAGTTCTG CACCCAGCGGATGCA CCCCTCTCCAAACAC ATTTTCCAGTTCTGA ACCCAGCGGATGCAG CCCTCTCCAAACACC TTTTCCAGTTCTGAC CCCAGCGGATGCAGT CCTCTCCAAACACCG TTTCCAGTTCTGACA CCAGCGGATGCAGTA CTCTCCAAACACCGG TTCCAGTTCTGACAC CAGCGGATGCAGTAG TCTCCAAACACCGGC TCCAGTTCTGACACA AGCGGATGCAGTAGA CTCCAAACACCGGCA CCAGTTCTGACACAC GCGGATGCAGTAGAC TCCAAACACCGGCAG CAGTTCTGACACACG CGGATGCAGTAGACC CCAAACACCGGCAGA AGTTCTGACACACGT GGATGCAGTAGACCG CAAACACCGGCAGAA GTTCTGACACACGTA GATGCAGTAGACCGC AAACACCGGCAGAAA TTCTGACACACGTAT ATGCAGTAGACCGCA AACACCGGCAGAAAA TCTGACACACGTATT TGCAGTAGACCGCAG ACACCGGCAGAAAAC CTGACACACGTATTT GCAGTAGACCGCAGC CACCGGCAGAAAACG TGACACACGTATTTA CAGTAGACCGCAGCC ACCGGCAGAAAACGG GACACACGTATTTAT AGTAGACCGCAGCCA CCGGCAGAAAACGGA ACACACGTATTTATA GTAGACCGCAGCCAG CGGCAGAAAACGGAG CACACGTATTTATAT TAGACCGCAGCCAGC GGCAGAAAACGGAGA ACACGTATTTATATT AGACCGCAGCCAGCC GCAGAAAACGGAGAG CACGTATTTATATTT GACCGCAGCCAGCCG CAGAAAACGGAGAGT ACGTATTTATATTTG ACCGCAGCCAGCCGG AGAAAACGGAGAGTG CGTATTTATATTTGG CCGCAGCCAGCCGGT GAAAACGGAGAGTGC GTATTTATATTTGGA CGCAGCCAGCCGGTG AAAACGGAGAGTGCT TATTTATATTTGGAA GCAGCCAGCCGGTGC AAACGGAGAGTGCTT ATTTATATTTGGAAA CAGCCAGCCGGTGCC AACGGAGAGTGCTTG TTTATATTTGGAAAG AGCCAGCCGGTGCCT ACGGAGAGTGCTTGG TTATATTTGGAAAGA GCCAGCCGGTGCCTG CGGAGAGTGCTTGGG TATATTTGGAAAGAG CCAGCCGGTGCCTGG GGAGAGTGCTTGGGT ATATTTGGAAAGAGA CAGCCGGTGCCTGGC GAGAGTGCTTGGGTG TATTTGGAAAGAGAC AGCCGGTGCCTGGCG AGAGTGCTTGGGTGG ATTTGGAAAGAGACC GCCGGTGCCTGGCGC GAGTGCTTGGGTGGT TTTGGAAAGAGACCA CCGGTGCCTGGCGCC AGTGCTTGGGTGGTG TTGGAAAGAGACCAG CGGTGCCTGGCGCCC GTGCTTGGGTGGTGG TGGAAAGAGACCAGC GGTGCCTGGCGCCCC TGCTTGGGTGGTGGG GGAAAGAGACCAGCA GTGCCTGGCGCCCCT GCTTGGGTGGTGGGT GAAAGAGACCAGCAC TGCCTGGCGCCCCTG CTTGGGTGGTGGGTG AAAGAGACCAGCACC GCCTGGCGCCCCTGC TTGGGTGGTGGGTGC AAGAGACCAGCACCG CCTGGCGCCCCTGCC TGGGTGGTGGGTGCT AGAGACCAGCACCGA CTGGCGCCCCTGCCC GGGTGGTGGGTGCTG GAGACCAGCACCGAG TGGCGCCCCTGCCCC GGTGGTGGGTGCTGG AGACCAGCACCGAGC GACCAGCACCGAGCT CACCTGCTCCTTCTT GGGTACAGGTTTGGG ACCAGCACCGAGCTC ACCTGCTCCTTCTTG GGTACAGGTTTGGGG CCAGCACCGAGCTCG CCTGCTCCTTCTTGC GTACAGGTTTGGGGA CAGCACCGAGCTCGG CTGCTCCTTCTTGCT TACAGGTTTGGGGAG AGCACCGAGCTCGGC TGCTCCTTCTTGCTT ACAGGTTTGGGGAGG GCACCGAGCTCGGCA GCTCCTTCTTGCTTT CAGGTTTGGGGAGGG CACCGAGCTCGGCAC CTCCTTCTTGCTTTC AGGTTTGGGGAGGGG ACCGAGCTCGGCACC TCCTTCTTGCTTTCC GGTTTGGGGAGGGGG CCGAGCTCGGCACCT CCTTCTTGCTTTCCC CTTTGGGGAGGGGGA CGAGCTCGGCACCTC CTTCTTGCTTTCCCC TTTGGGGAGGGGGAA GAGCTCGGCACCTCC TTCTTGCTTTCCCCG TTGGGGAGGGGGAAG AGCTCGGCACCTCCC TCTTGCTTTCCCCGC TGGGGAGGGGGAAGA GCTCGGCACCTCCCC CTTGCTTTCCCCGGG GGGGAGGGGGAAGAG CTCGGCACCTCCCCG TTGCTTTCCCCGGGG GGGAGGGGGAAGAGA TCGGCACCTCCCCGG TGCTTTCCCCGGGGG GGAGGGGGAAGAGAA CGGCACCTCCCCGGC GCTTTCCCCGGGGGA GAGGGGGAAGAGAAA GGCACCTCCCCGGCC CTTTCCCCGGGGGAG AGGGGGAAGAGAAAT GCACCTCCCCGGCCT TTTCCCCGGGGGAGG GGGGGAAGAGAAATT CACCTCCCCGGCCTC TTCCCCGGGGGAGGA GGGGAAGAGAAATTT ACCTCCCCGGCCTCT TCCCCGGGGGAGGAA GGGAAGAGAAATTTT CCTCCCCGGCCTCTC CCCCGGGGGAGGAAG GGAAGAGAAATTTTT CTCCCCGGCCTCTCT CCCGGGGGAGGAAGG GAAGAGAAATTTTTA TCCCCGGCCTCTCTC CCGGGGGAGGAAGGG AAGAGAAATTTTTAT CCCCGGCCTCTCTCT CGGGGGAGGAAGGGG AGAGAAATTTTTATT CCCGGCCTCTCTCTT GGGGGAGGAAGGGGG GAGAAATTTTTATTT CCGGCCTCTCTCTTC GGGGAGGAAGGGGGT AGAAATTTTTATTTT CGGCCTCTCTCTTCC GGGAGGAAGGGGGTT GAAATTTTTATTTTT GGCCTCTCTCTTCCC GGAGGAAGGGGGTTG AAATTTTTATTTTTG GCCTCTCTCTTCCCA GAGGAAGGGGGTTGT AATTTTTATTTTTGA CCTCTCTCTTCCCAG AGGAAGGGGGTTGTG ATTTTTATTTTTGAA CTCTCTCTTCCCAGC GGAAGGGGGTTGTGG TTTTTATTTTTGAAC TCTCTCTTCCCAGCT GAAGGGGGTTGTGGT TTTTATTTTTGAACC CTCTCTTCCCAGCTG AAGGGGGTTGTGGTC TTTATTTTTGAACCC TCTCTTCCCAGCTGC AGGGGGTTGTGGTCG TTATTTTTGAACCCC CTCTTCCCAGCTGCA GGGGGTTGTGGTCGG TATTTTTGAACCCCT TCTTCCCAGCTGCAG GGGGTTGTGGTCGGG ATTTTTGAACCCCTG CTTCCCAGCTGCAGA GGGTTGTGGTCGGGG TTTTTGAACCCCTGT TTCCCAGCTGCAGAT GGTTGTGGTCGGGGA TTTTGAACCCCTGTG TCCCAGCTGCAGATG GTTGTGGTCGGGGAG TTTGAACCCCTGTGT CCCAGCTGCAGATGC TTGTGGTCGGGGAGC TTGAACCCCTGTGTC CCAGCTGCAGATGCC TGTGGTCGGGGAGCT TGAACCCCTGTGTCC CAGCTGCAGATGCCA GTGGTCGGGGAGCTG GAACCCCTGTGTCCC AGCTGCAGATGCCAC TGGTCGGGGAGCTGG AACCCCTGTGTCCCT GCTGCAGATGCCACA GGTCGGGGAGCTGGG ACCCCTGTGTCCCTT CTGCAGATGCCACAC GTCGGGGAGCTGGGG CCCCTGTGTCCCTTT TGCAGATGCCACACC TCGGGGAGCTGGGGT CCCTGTGTCCCTTTT GCAGATGCCACACCT CGGGGAGCTGGGGTA CCTGTGTCCCTTTTG CAGATGCCACACCTG GGGGAGCTGGGGTAC CTGTGTCCCTTTTGC AGATGCCACACCTGC GGGAGCTGGGGTACA TGTGTCCCTTTTGCA GATGCCACACCTGCT GGAGCTGGGGTACAG GTGTCCCTTTTGCAT ATGCCACACCTGCTC GAGCTGGGGTACAGG TGTCCCTTTTGCATA TGCCACACCTGCTCC AGCTGGGGTACAGGT GTCCCTTTTGCATAA GCCACACCTGCTCCT GCTGGGGTACAGGTT TCCCTTTTGCATAAG CCACACCTGCTCCTT CTGGGGTACAGGTTT CCCTTTTGCATAAGA CACACCTGCTCCTTC TGGGGTACAGGTTTG CCTTTTGCATAAGAT ACACCTGCTCCTTCT GGGGTACAGGTTTGG CTTTTGCATAAGATT TTTTGCATAAGATTA TTTGCATAAGATTAA TTGCATAAGATTAAA TGCATAAGATTAAAG GCATAAGATTAAAGG CATAAGATTAAAGGA ATAAGATTAAAGGAA TAAGATTAAAGGAAG AAGATTAAAGGAAGG AGATTAAAGGAAGGA GATTAAAGGAAGGAA ATTAAAGGAAGGAAA TTAAAGGAAGGAAAA TAAAGGAAGGAAAAG AAAGGAAGGAAAAGT
EXAMPLE 7 Antisense Oligonucleotides of IGFBP3[0057] Antisense oligonucleotides to IGFBP3 may be selected from molecules capable of interacting with one or more of the following sense oligonucleotides: 5 CTCAGCGCCCAGCCG CCACAGCTTCGCGCC ATCCCTGCGCGCCCA TCAGCGCCCAGCCGC CACAGCTTCGCGCCG TCCCTGCGCGCCCAG CAGCGCCCAGCCGCT ACAGCTTCGCGCCGT CCCTGCGCGCCCAGC AGCGCCCAGCCGCTT CAGCTTCGCGCCGTG CCTGCGCGCCCAGCC GCGCCCAGCCGCTTC AGCTTCGCGCCGTGT CTGCGCGCCCAGCCT CGCCCAGCCGCTTCC GCTTCGCGCCGTGTA TGCGCGCCCAGCCTG GCCCAGCCGCTTCCT CTTCGCGCCGTGTAC GCGCGCCCAGCCTGC CCCAGCCGCTTCCTG TTCGCGCCGTGTACT CGCGCCCAGCCTGCC CCAGCCGCTTCCTGC TCGCGCCGTGTACTG GCGCCCAGCCTGCCA CAGCCGCTTCCTGCC CGCGCCGTGTACTGT CGCCCAGCCTGCCAA AGCCGCTTCCTGCCT GCGCCGTGTACTGTC GCCCAGCCTGCCAAG GCCGCTTCCTGCCTG CGCCGTGTACTGTCG CCCAGCCTGCCAAGC CCGCTTCCTGCCTGG GCCGTGTACTGTCGC CCAGCCTGCCAAGCA CGCTTCCTGCCTGGA CCGTGTACTGTCGCC CAGCCTGCCAAGCAG GCTTCCTGCCTGGAT CGTGTACTGTCGCCC AGCCTGCCAAGCAGC CTTCCTGCCTGGATT GTGTACTGTCGCCCC GCCTGCCAAGCAGCG TTCCTGCCTGGATTC TGTACTGTCGCCCCA CCTGCCAAGCAGCGT TCCTGCCTGGATTCC GTACTGTCGCCCCAT CTGCCAAGCAGCGTG CCTGCCTGGATTCCA TACTGTCGCCCCATC TGCCAAGCAGCGTGC CTGCCTGGATTCCAC ACTGTCGCCCCATCC GCCAAGCAGCGTGCC TGCCTGGATTCCACA CTGTCGCCCCATCCC CCAAGCAGCGTGCCC GCCTGGATTCCACAG TGTCGCCCCATCCCT CAAGCAGCGTGCCCC CCTGGATTCCACAGC GTCGCCCCATCCCTG AAGCAGCGTGCCCCG CTGGATTCCACAGCT TCGCCCCATCCCTGC AGCAGCGTGCCCCGG TGGATTCCACAGCTT CGCCCCATCCCTGCG GCAGCGTGCCCCGGT GGATTCCACAGCTTC GCCCCATCCCTGCGC CAGCGTGCCCCGGTT GATTCCACAGCTTCG CCCCATCCCTGCGCG AGCGTGCCCCGGTTG ATTCCACAGCTTCGC CCCATCCCTGCGCGC GCGTGCCCCGGTTGC TTCCACAGCTTCGCG CCATCCCTGCGCGCC CGTGCCCCGGTTGCA TCCACAGCTTCGCGC CATCCCTGCGCGCCC GTGCCCCGGTTGCAG TGCCCCGGTTGCAGG TGACTCTGCTGGTGC GGGGGCTTGGGTCCC GCCCCGGTTGCAGGC GACTCTGCTGGTGCT GGGGCTTGGGTCCCG CCCCGGTTGCAGGCG ACTCTGCTGGTGCTG GGGCTTGGGTCCCGT CCCGGTTGCAGGCGT CTCTGCTGGTGCTGC GGCTTGGGTCCCGTG CCGGTTGCAGGCGTC TCTGCTGGTGCTGCT GCTTGGGTCCCGTGG CGGTTGCAGGCGTCA CTGCTGGTGCTGCTC CTTGGGTCCCGTGGT GGTTGCAGGCGTCAT TGCTGGTGCTGCTCC TTGGGTCCCGTGGTG GTTGCAGGCGTCATG GCTGGTGCTGCTCCG TGGGTCCCGTGGTGC TTGCAGGCGTCATGC CTGGTGCTGCTCCGC GGGTCCCGTGGTGCG TGCAGGCGTCATGCA TGGTGCTGCTCCGCG GGTCCCGTGGTGCGC GCAGGCGTCATGCAG GGTGCTGCTCCGCGG GTCCCGTGGTGCGCT CAGGCGTCATGCAGC GTGCTGCTCCGCGGG TCCCGTGGTGCGCTG AGGCGTCATGCAGCG TGCTGCTCCGCGGGC CCCGTGGTGCGCTGC GGCGTCATGCAGCGG GCTGCTCCGCGGGCC CCGTGGTGCGCTGCG GCGTCATGCAGCGGG CTGCTCCGCGGGCCG CGTGGTGCGCTGCGA CGTCATGCAGCGGGC TGCTCCGCGGGCCGC GTGGTGCGCTGCGAG GTCATGCAGCGGGCG GCTCCGCGGGCCGCC TGGTGCGCTGCGAGC TCATGCAGCGGGCGC CTCCGCGGGCCGCCG GGTGCGCTGCGAGCC CATGCAGCGGGCGCG TCCGCGGGCCGCCGG GTGCGCTGCGAGCCG ATGCAGCGGGCGCGA CCGCGGGCCGCCGGT TGCGCTGCGAGCCGT TGCAGCGGGCGCGAC CGCGGGCCGCCGGTG GCGCTGCGAGCCGTG GCAGCGGGCGCGACC GCGGGCCGCCGGTGG CGCTGCGAGCCGTGC CAGCGGGCGCGACCC CGGGCCGCCGGTGGC GCTGCGAGCCGTGCG AGCGGGCGCGACCCA GGGCCGCCGGTGGCG CTGCGAGCCGTGCGA GCGGGCGCGACCCAC GGCCGCCGGTGGCGC TGCGAGCCGTGCGAC CGGGCGCGACCCACG GCCGCCGGTGGCGCG GCGAGCCGTGCGACG GGGCGCGACCCACGC CCGCCGGTGGCGCGG CGAGCCGTGCGACGC GGCGCGACCCACGCT CGCCGGTGGCGCGGG GAGCCGTGCGACGCG GCGCGACCCACGCTC GCCGGTGGCGCGGGC AGCCGTGCGACGCGC CGCGACCCACGCTCT CCGGTGGCGCGGGCT GCCGTGCGACGCGCG GCGACCCACGCTCTG CGGTGGCGCGGGCTG CCGTGCGACGCGCGT CGACCCACGCTCTGG GGTGGCGCGGGCTGG CGTGCGACGCGCGTG GACCCACGCTCTGGG GTGGCGCGGGCTGGC GTGCGACGCGCGTGC ACCCACGCTCTGGGC TGGCGCGGGCTGGCG TGCGACGCGCGTGCA CCCACGCTCTGGGCC GGCGCGGGCTGGCGC GCGACGCGCGTGCAC CCACGCTCTGGGCCG GCGCGGGCTGGCGCG CGACGCGCGTGCACT CACGCTCTGGGCCGC CGCGGGCTGGCGCGA GACGCGCGTGCACTG ACGCTCTGGGCCGCT GCGGGCTGGCGCGAG ACGCGCGTGCACTGG CGCTCTGGGCCGCTG CGGGCTGGCGCGAGC CGCGCGTGCACTGGC GCTCTGGGCCGCTGC GGGCTGGCGCGAGCT GCGCGTGCACTGGCC CTCTGGGCCGCTGCG GGCTGGCGCGAGCTC CGCGTGCACTGGCCC TCTGGGCCGCTGCGC GCTGGCGCGAGCTCG GCGTGCACTGGCCCA CTGGGCCGCTGCGCT CTGGCGCGAGCTCGG CGTGCACTGGCCCAG TGGGCCGCTGCGCTG TGGCGCGAGCTCGGG GTGCACTGGCCCAGT GGGCCGCTGCGCTGA GGCGCGAGCTCGGGG TGCACTGGCCCAGTG GGCCGCTGCGCTGAC GCGCGAGCTCGGGGG GCACTGGCCCAGTGC GCCGCTGCGCTGACT CGCGAGCTCGGGGGG CACTGGCCCAGTGCG CCGCTGCGCTGACTC GCGAGCTCGGGGGGC ACTGGCCCAGTGCGC CGCTGCGCTGACTCT CGAGCTCGGGGGGCT CTGGCCCAGTGCGCG GCTGCGCTGACTCTG GAGCTCGGGGGGCTT TGGCCCAGTGCGCGC CTGCGCTGACTCTGC AGCTCGGGGGGCTTG GGCCCAGTGCGCGCC TGCGCTGACTCTGCT GCTCGGGGGGCTTGG GCCCAGTGCGCGCCT GCGCTGACTCTGCTG CTCGGGGGGCTTGGG CCCAGTGCGCGCCTC CGCTGACTCTGCTGG TCGGGGGGCTTGGGT CCAGTGCGCGCCTCC GCTGACTCTGCTGGT CGGGGGGCTTGGGTC CAGTGCGCGCCTCCG CTGACTCTGCTGGTG GGGGGGCTTGGGTCC AGTGCGCGCCTCCGC GTGCGCGCCTCCGCC GCTGCCTGACGTGCG TGTGGCTCCGGCCTT TGCGCGCCTCCGCCC CTGCCTGACGTGCGC GTGGCTCCGGCCTTC GCGCGCCTCCGCCCG TGCCTGACGTGCGCA TGGCTCCGGCCTTCG CGCGCCTCCGCCCGC GCCTGACGTGCGCAC GGCTCCGGCCTTCGC GCGCCTCCGCCCGCC CCTGACGTGCGCACT GCTCCGGCCTTCGCT CGCCTCCGCCCGCCG CTGACGTGCGCACTG CTCCGGCCTTCGCTG GCCTCCGCCCGCCGT TGACGTGCGCACTGA TCCGGCCTTCGCTGC CCTCCGCCCGCCGTG GACGTGCGCACTGAG CCGGCCTTCGCTGCC CTCCGCCCGCCGTGT ACGTGCGCACTGAGC CGGCCTTCGCTGCCA TCCGCCCGCCGTGTG CGTGCGCACTGAGCG GGCCTTCGCTGCCAG CCGCCCGCCGTGTGC GTGCGCACTGAGCGA GCCTTCGCTGCCAGC CGCCCGCCGTGTGCG TGCGCACTGAGCGAG CCTTCGCTGCCAGCC GCCCGCCGTGTGCGC GCGCACTGAGCGAGG CTTCGCTGCCAGCCG CCCGCCGTGTGCGCG CGCACTGAGCGAGGG TTCGCTGCCAGCCGT CCGCCGTGTGCGCGG GCACTGAGCGAGGGC TCGCTGCCAGCCGTC CGCCGTGTGCGCGGA CACTGAGCGAGGGCC CGCTGCCAGCCGTCG GCCGTGTGCGCGGAG ACTGAGCGAGGGCCA GCTGCCAGCCGTCGC CCGTGTGCGCGGAGC CTGAGCGAGGGCCAG CTGCCAGCCGTCGCC CGTGTGCGCGGAGCT TGAGCGAGGGCCAGC TGCCAGCCGTCGCCC GTGTGCGCGGAGCTG GAGCGAGGGCCAGCC GCCAGCCGTCGCCCG TGTGCGCGGAGCTGG AGCGAGGGCCAGCCG CCAGCCGTCGCCCGA GTGCGCGGAGCTGGT GCGAGGGCCAGCCGT CAGCCGTCGCCCGAC TGCGCGGAGCTGGTG CGAGGGCCAGCCGTG AGCCGTCGCCCGACG GCGCGGAGCTGGTGC GAGGGCCAGCCGTGC GCCGTCGCCCGACGA CGCGGAGCTGGTGCG AGGGCCAGCCGTGCG CCGTCGCCCGACGAG GCGGAGCTGGTGCGC GGGCCAGCCGTGCGG CGTCGCCCGACGAGG CGGAGCTGGTGCGCG GGCCAGCCGTGCGGC GTCGCCCGACGAGGC GGAGCTGGTGCGCGA GCCAGCCGTGCGGCA TCGCCCGACGAGGCG GAGCTGGTGCGCGAG CCAGCCGTGCGGCAT CGCCCGACGAGGCGC AGCTGGTGCGCGAGC CAGCCGTGCGGCATC GCCCGACGAGGCGCG GCTGGTGCGCGAGCC AGCCGTGCGGCATCT CCCGACGAGGCGCGA CTGGTGCGCGAGCCG GCCGTGCGGCATCTA CCGACGAGGCGCGAC TGGTGCGCGAGCCGG CCGTGCGGCATCTAC CGACGAGGCGCGACC GGTGCGCGAGCCGGG CGTGCGGCATCTACA GACGAGGCGCGACCG GTGCGCGAGCCGGGC GTGCGGCATCTACAC ACGAGGCGCGACCGC TGCGCGAGCCGGGCT TGCGGCATCTACACC CGAGGCGCGACCGCT GCGCGAGCCGGGCTG GCGGCATCTACACCG GAGGCGCGACCGCTG CGCGAGCCGGGCTGC CGGCATCTACACCGA AGGCGCGACCGCTGC GCGAGCCGGGCTGCG GGCATCTACACCGAG GGCGCGACCGCTGCA CGAGCCGGGCTGCGG GCATCTACACCGAGC GCGCGACCGCTGCAG GAGCCGGGCTGCGGC CATCTACACCGAGCG CGCGACCGCTGCAGG AGCCGGGCTGCGGCT ATCTACACCGAGCGC GCGACCGCTGCAGGC GCCGGGCTGCGGCTG TCTACACCGAGCGCT CGACCGCTGCAGGCG CCGGGCTGCGGCTGC CTACACCGAGCGCTG GACCGCTGCAGGCGC CGGGCTGCGGCTGCT TACACCGAGCGCTGT ACCGCTGCAGGCGCT GGGCTGCGGCTGCTG ACACCGAGCGCTGTG CCGCTGCAGGCGCTG GGCTGCGGCTGCTGC CACCGAGCGCTGTGG CGCTGCAGGCGCTGC GCTGCGGCTGCTGCC ACCGAGCGCTGTGGC GCTGCAGGCGCTGCT CTGCGGCTGCTGCCT CCGAGCGCTGTGGCT CTGCAGGCGCTGCTG TGCGGCTGCTGCCTG CGAGCGCTGTGGCTC TGCAGGCGCTGCTGG GCGGCTGCTGCCTGA GAGCGCTGTGGCTCC GCAGGCGCTGCTGGA CGGCTGCTGCCTGAC AGCGCTGTGGCTCCG CAGGCGCTGCTGGAC GGCTGCTGCCTGACG GCGCTGTGGCTCCGG AGGCGCTGCTGGACG GCTGCTGCCTGACGT CGCTGTGGCTCCGGC GGCGCTGCTGGACGG CTGCTGCCTGACGTG GCTGTGGCTCCGGCC GCGCTGCTGGACGGC TGCTGCCTGACGTGC CTGTGGCTCCGGCCT CGCTGCTGGACGGCC GCTGCTGGACGGCCG CCTACCTGCTGCCAG CGCAGCGCCGGCAGT CTGCTGGACGGCCGC CTACCTGCTGCCAGC GCAGCGCCGGCAGTG TGCTGGACGGCCGCG TACCTGCTGCCAGCG CAGCGCCGGCAGTGT GCTGGACGGCCGCGG ACCTGCTGCCAGCGC AGCGCCGGCAGTGTG CTGGACGGCCGCGGG CCTGCTGCCAGCGCC GCGCCGGCAGTGTGG TGGACGGCCGCGGGC CTGCTGCCAGCGCCG CGCCGGCAGTGTGGA GGACGGCCGCGGGCT TGCTGCCAGCGCCGC GCCGGCAGTGTGGAG GACGGCCGCGGGCTC GCTGCCAGCGCCGCC CCGGCAGTGTGGAGA ACGGCCGCGGGCTCT CTGCCAGCGCCGCCA CGGCAGTGTGGAGAG CGGCCGCGGGCTCTG TGCCAGCGCCGCCAG GGCAGTGTGGAGAGC GGCCGCGGGCTCTGC GCCAGCGCCGCCAGC GCAGTGTGGAGAGCC GCCGCGGGCTCTGCG CCAGCGCCGCCAGCT CAGTGTGGAGAGCCC CCGCGGGCTCTGCGT CAGCGCCGCCAGCTC AGTGTGGAGAGCCCG CGCGGGCTCTGCGTC AGCGCCGCCAGCTCC GTGTGGAGAGCCCGT GCGGGCTCTGCGTCA GCGCCGCCAGCTCCA TGTGGAGAGCCCGTC CGGGCTCTGCGTCAA CGCCGCCAGCTCCAG GTGGAGAGCCCGTCC GGGCTCTGCGTCAAC GCCGCCAGCTCCAGG TGGAGAGCCCGTCCG GGCTCTGCGTCAACG CCGCCAGCTCCAGGA GGAGAGCCCGTCCGT GCTCTGCGTCAACGC CGCCAGCTCCAGGAA GAGAGCCCGTCCGTC CTCTGCGTCAACGCT GCCAGCTCCAGGAAA AGAGCCCGTCCGTCT TCTGCGTCAACGCTA CCAGCTCCAGGAAAT GAGCCCGTCCGTCTC CTGCGTCAACGCTAG CAGCTCCAGGAAATG AGCCCGTCCGTCTCC TGCGTCAACGCTAGT AGCTCCAGGAAATGC GCCCGTCCGTCTCCA GCGTCAACGCTAGTG GCTCCAGGAAATGCT CCCGTCCGTCTCCAG CGTCAACGCTAGTGC CTCCAGGAAATGCTA CCGTCCGTCTCCAGC GTCAACGCTAGTGCC TCCAGGAAATGCTAG CGTCCGTCTCCAGCA TCAACGCTAGTGCCG CCAGGAAATGCTAGT GTCCGTCTCCAGCAC CAACGCTAGTGCCGT CAGGAAATGCTAGTG TCCGTCTCCAGCACG AACGCTAGTGCCGTC AGGAAATGCTAGTGA CCGTCTCCAGCACGC ACGCTAGTGCCGTCA GGAAATGCTAGTGAG CGTCTCCAGCACGCA CGCTAGTGCCGTCAG GAAATGCTAGTGAGT GTCTCCAGCACGCAC GCTAGTGCCGTCAGC AAATGCTAGTGAGTC TCTCCAGCACGCACC CTAGTGCCGTCAGCC AATGCTAGTGAGTCG CTCCAGCACGCACCG TAGTGCCGTCAGCCG ATGCTAGTGAGTCGG TCCAGCACGCACCGG AGTGCCGTCAGCCGC TGCTAGTGAGTCGGA CCAGCACGCACCGGG GTGCCGTCAGCCGCC GCTAGTGAGTCGGAG CAGCACGCACCGGGT TGCCGTCAGCCGCCT CTAGTGAGTCGGAGG AGCACGCACCGGGTG GCCGTCAGCCGCCTG TAGTGAGTCGGAGGA GCACGCACCGGGTGT CCGTCAGCCGCCTGC AGTGAGTCGGAGGAA CACGCACCGGGTGTC CGTCAGCCGCCTGCG GTGAGTCGGAGGAAG ACGCACCGGGTGTCT GTCAGCCGCCTGCGC TGAGTCGGAGGAAGA CGCACCGGGTGTCTG TCAGCCGCCTGCGCG GAGTCGGAGGAAGAC GCACCGGGTGTCTGA CAGCCGCCTGCGCGC AGTCGGAGGAAGACC CACCGGGTGTCTGAT AGCCGCCTGCGCGCC GTCGGAGGAAGACCG ACCGGGTGTCTGATC GCCGCCTGCGCGCCT TCGGAGGAAGACCGC CCGGGTGTCTGATCC CCGCCTGCGCGCCTA CGGAGGAAGACCGCA CGGGTGTCTGATCCC CGCCTGCGCGCCTAC GGAGGAAGACCGCAG GGGTGTCTGATCCCA GCCTGCGCGCCTACC GAGGAAGACCGCAGC GGTGTCTGATCCCAA CCTGCGCGCCTACCT AGGAAGACCGCAGCG GTGTCTGATCCCAAG CTGCGCGCCTACCTG GGAAGACCGCAGCGC TGTCTGATCCCAAGT TGCGCGCCTACCTGC GAAGACCGCAGCGCC GTCTGATCCCAAGTT GCGCGCCTACCTGCT AAGACCGCAGCGCCG TCTGATCCCAAGTTC CGCGCCTACCTGCTG AGACCGCAGCGCCGG CTGATCCCAAGTTCC GCGCCTACCTGCTGC GACCGCAGCGCCGGC TGATCCCAAGTTCCA CGCCTACCTGCTGCC ACCGCAGCGCCGGCA GATCCCAAGTTCCAC GCCTACCTGCTGCCA CCGCAGCGCCGGCAG ATCCCAAGTTCCACC TCCCAAGTTCCACCC AAGACAGCCAGCGCT TTCTCCTCCGAGTCC CCCAAGTTCCACCCC AGACAGCCAGCGCTA TCTCCTCCGAGTCCA CCAAGTTCCACCCCC GACAGCCAGCGCTAC CTCCTCCGAGTCCAA CAAGTTCCACCCCCT ACAGCCAGCGCTACA TCCTCCGAGTCCAAG AAGTTCCACCCCCTC CAGCCAGCGCTACAA CCTCCGAGTCCAAGC AGTTCCACCCCCTCC AGCCAGCGCTACAAA CTCCGAGTCCAAGCG GTTCCACCCCCTCCA GCCAGCGCTACAAAG TCCGAGTCCAAGCGG TTCCACCCCCTCCAT CCAGCGCTACAAAGT CCGAGTCCAAGCGGG TCCACCCCCTCCATT CAGCGCTACAAAGTT CGAGTCCAAGCGGGA CCACCCCCTCCATTC AGCGCTACAAAGTTG GAGTCCAAGCGGGAG CACCCCCTCCATTCA GCGCTACAAAGTTGA AGTCCAAGCGGGAGA ACCCCCTCCATTCAA CGCTACAAAGTTGAC GTCCAAGCGGGAGAC CCCCCTCCATTCAAA GCTACAAAGTTGACT TCCAAGCGGGAGACA CCCCTCCATTCAAAG CTACAAAGTTGACTA CCAAGCGGGAGACAG CCCTCCATTCAAAGA TACAAAGTTGACTAC CAAGCGGGAGACAGA CCTCCATTCAAAGAT ACAAAGTTGACTACG AAGCGGGAGACAGAA CTCCATTCAAAGATA CAAAGTTGACTACGA AGCGGGAGACAGAAT TCCATTCAAAGATAA AAAGTTGACTACGAG GCGGGAGACAGAATA CCATTCAAAGATAAT AAGTTGACTACGAGT CGGGAGACAGAATAT CATTCAAAGATAATC AGTTGACTACGAGTC GGGAGACAGAATATG ATTCAAAGATAATCA GTTGACTACGAGTCT GGAGACAGAATATGG TTCAAAGATAATCAT TTGACTACGAGTCTC GAGACAGAATATGGT TCAAAGATAATCATC TGACTACGAGTCTCA AGACAGAATATGGTC CAAAGATAATCATCA GACTACGAGTCTCAG GACAGAATATGGTCC AAAGATAATCATCAT ACTACGAGTCTCAGA ACAGAATATGGTCCC AAGATAATCATCATC CTACGAGTCTCAGAG CAGAATATGGTCCCT AGATAATCATCATCA TACGAGTCTCAGAGC AGAATATGGTCCCTG GATAATCATCATCAA ACGAGTCTCAGAGCA GAATATGGTCCCTGC ATAATCATCATCAAG CGAGTCTCAGAGCAC AATATGGTCCCTGCC TAATCATCATCAAGA GAGTCTCAGAGCACA ATATGGTCCCTGCCG AATCATCATCAAGAA AGTCTCAGAGCACAG TATGGTCCCTGCCGT ATCATCATCAAGAAA GTCTCAGAGCACAGA ATGGTCCCTGCCGTA TCATCATCAAGAAAG TCTCAGAGCACAGAT TGGTCCCTGCCGTAG CATCATCAAGAAAGG CTCAGAGCACAGATA GGTCCCTGCCGTAGA ATCATCAAGAAAGGG TCAGAGCACAGATAC GTCCCTGCCGTAGAG TCATCAAGAAAGGGC CAGAGCACAGATACC TCCCTGCCGTAGAGA CATCAAGAAAGGGCA AGAGCACAGATACCC CCCTGCCGTAGAGAA ATCAAGAAAGGGCAT GAGCACAGATACCCA CCTGCCGTAGAGAAA TCAAGAAAGGGCATG AGCACAGATACCCAG CTGCCGTAGAGAAAT CAAGAAAGGGCATGC GCACAGATACCCAGA TGCCGTAGAGAAATG AAGAAAGGGCATGCT CACAGATACCCAGAA GCCGTAGAGAAATGG AGAAAGGGCATGCTA ACAGATACCCAGAAC CCGTAGAGAAATGGA GAAAGGGCATGCTAA CAGATACCCAGAACT CGTAGAGAAATGGAA AAAGGGCATGCTAAA AGATACCCAGAACTT GTAGAGAAATGGAAG AAGGGCATGCTAAAG GATACCCAGAACTTC TAGAGAAATGGAAGA AGGGCATGCTAAAGA ATACCCAGAACTTCT AGAGAAATGGAAGAC GGGCATGCTAAAGAC TACCCAGAACTTCTC GAGAAATGGAAGACA GGCATGCTAAAGACA ACCCAGAACTTCTCC AGAAATGGAAGACAC GCATGCTAAAGACAG CCCAGAACTTCTCCT GAAATGGAAGACACA CATGCTAAAGACAGC CCAGAACTTCTCCTC AAATGGAAGACACAC ATGCTAAAGACAGCC CAGAACTTCTCCTCC AATGGAAGACACACT TGCTAAAGACAGCCA AGAACTTCTCCTCCG ATGGAAGACACACTG GCTAAAGACAGCCAG GAACTTCTCCTCCGA TGGAAGACACACTGA CTAAAGACAGCCAGC AACTTCTCCTCCGAG GGAAGACACACTGAA TAAAGACAGCCAGCG ACTTCTCCTCCGAGT GAAGACACACTGAAT AAAGACAGCCAGCGC CTTCTCCTCCGAGTC AAGACACACTGAATC AGACACACTGAATCA TTCCCAACTGTGACA GGCAGGAAGCGGGGC GACACACTGAATCAC TCCCAACTGTGACAA GCAGGAAGCGGGGCT ACACACTGAATCACC CCCAACTGTGACAAG CAGGAAGCGGGGCTT CACACTGAATCACCT CCAACTGTGACAAGA AGGAAGCGGGGCTTC ACACTGAATCACCTG CAACTGTGACAAGAA GGAAGCGGGGCTTCT CACTGAATCACCTGA AACTGTGACAAGAAG GAAGCGGGGCTTCTG ACTGAATCACCTGAA ACTGTGACAAGAAGG AAGCGGGGCTTCTGC CTGAATCACCTGAAG CTGTGACAAGAAGGG AGCGGGGCTTCTGCT TGAATCACCTGAAGT TGTGACAAGAAGGGA GCGGGGCTTCTGCTG GAATCACCTGAAGTT GTGACAAGAAGGGAT CGGGGCTTCTGCTGG AATCACCTGAAGTTC TGACAAGAAGGGATT GGGGCTTCTGCTGGT ATCACCTGAAGTTCC GACAAGAAGGGATTT GGGCTTCTGCTGGTG TCACCTGAAGTTCCT ACAAGAAGGGATTTT GGCTTCTGCTGGTGT CACCTGAAGTTCCTC CAAGAAGGGATTTTA GCTTCTGCTGGTGTG ACCTGAAGTTCCTCA AAGAAGGGATTTTAT CTTCTGCTGGTGTGT CCTGAAGTTCCTCAA AGAAGGGATTTTATA TTCTGCTGGTGTGTG CTGAAGTTCCTCAAT GAAGGGATTTTATAA TCTGCTGGTGTGTGG TGAAGTTCCTCAATG AAGGGATTTTATAAG CTGCTGGTGTGTGGA GAAGTTCCTCAATGT AGGGATTTTATAAGA TGCTGGTGTGTGGAT AAGTTCCTCAATGTG GGGATTTTATAAGAA GCTGGTGTGTGGATA AGTTCCTCAATGTGC GGATTTTATAAGAAA CTGGTGTGTGGATAA GTTCCTCAATGTGCT GATTTTATAAGAAAA TGGTGTGTGGATAAG TTCCTCAATGTGCTG ATTTTATAAGAAAAA GGTGTGTGGATAAGT TCCTCAATGTGCTGA TTTTATAAGAAAAAG GTGTGTGGATAAGTA CCTCAATGTGCTGAG TTTATAAGAAAAAGC TGTGTGGATAAGTAT CTCAATGTGCTGAGT TTATAAGAAAAAGCA GTGTGGATAAGTATG TCAATGTGCTGAGTC TATAAGAAAAAGCAG TGTGGATAAGTATGG CAATGTGCTGAGTCC ATAAGAAAAAGCAGT GTGGATAAGTATGGG AATGTGCTGAGTCCC TAAGAAAAAGCAGTG TGGATAAGTATGGGC ATGTGCTGAGTCCCA AAGAAAAAGCAGTGT GGATAAGTATGGGCA TGTGCTGAGTCCCAG AGAAAAAGCAGTGTC GATAAGTATGGGCAG GTGCTGAGTCCCAGG GAAAAAGCAGTGTCG ATAAGTATGGGCAGC TGCTGAGTCCCAGGG AAAAAGCAGTGTCGC TAAGTATGGGCAGCC GCTGAGTCCCAGGGG AAAAGCAGTGTCGCC AAGTATGGGCAGCCT CTGAGTCCCAGGGGT AAAGCAGTGTCGCCC AGTATGGGCAGCCTC TGAGTCCCAGGGGTG AAGCAGTGTCGCCCT GTATGGGCAGCCTCT GAGTCCCAGGGGTGT AGCAGTGTCGCCCTT TATGGGCAGCCTCTC AGTCCCAGGGGTGTA GCAGTGTCGCCCTTC ATGGGCAGCCTCTCC GTCCCAGGGGTGTAC CAGTGTCGCCCTTCC TGGGCAGCCTCTCCC TCCCAGGGGTGTACA AGTGTCGCCCTTCCA GGGCAGCCTCTCCCA CCCAGGGGTGTACAC GTGTCGCCCTTCCAA GGCAGCCTCTCCCAG CCAGGGGTGTACACA TGTCGCCCTTCCAAA GCAGCCTCTCCCAGG CAGGGGTGTACACAT GTCGCCCTTCCAAAG CAGCCTCTCCCAGGC AGGGGTGTACACATT TCGCCCTTCCAAAGG AGCCTCTCCCAGGCT GGGGTGTACACATTC CGCCCTTCCAAAGGC GCCTCTCCCAGGCTA GGGTGTACACATTCC GCCCTTCCAAAGGCA CCTCTCCCAGGCTAC GGTGTACACATTCCC CCCTTCCAAAGGCAG CTCTCCCAGGCTACA GTGTACACATTCCCA CCTTCCAAAGGCAGG TCTCCCAGGCTACAC TGTACACATTCCCAA CTTCCAAAGGCAGGA CTCCCAGGCTACACC GTACACATTCCCAAC TTCCAAAGGCAGGAA TCCCAGGCTACACCA TACACATTCCCAACT TCCAAAGGCAGGAAG CCCAGGCTACACCAC ACACATTCCCAACTG CCAAAGGCAGGAAGC CCAGGCTACACCACC CACATTCCCAACTGT CAAAGGCAGGAAGCG CAGGCTACACCACCA ACATTCCCAACTGTG AAAGGCAGGAAGCGG AGGCTACACCACCAA CATTCCCAACTGTGA AAGGCAGGAAGCGGG GGCTACACCACCAAG ATTCCCAACTGTGAC AGGCAGGAAGCGGGG GCTACACCACCAAGG CTACACCACCAAGGG CGCCTGCCGCAAGTT CCAAGGACATGACCA TACACCACCAAGGGG GCCTGCCGCAAGTTA CAAGGACATGACCAG ACACCACCAAGGGGA CCTGCCGCAAGTTAA AAGGACATGACCAGC CACCACCAAGGGGAA CTGCCGCAAGTTAAT AGGACATGACCAGCA ACCACCAAGGGGAAG TGCCGCAAGTTAATG GGACATGACCAGCAG CCACCAAGGGGAAGG GCCGCAAGTTAATGT GACATGACCAGCAGC CACCAAGGGGAAGGA CCGCAAGTTAATGTG ACATGACCAGCAGCT ACCAAGGGGAAGGAG CGCAAGTTAATGTGG CATGACCAGCAGCTG CCAAGGGGAAGGAGG GCAAGTTAATGTGGA ATGACCAGCAGCTGG CAAGGGGAAGGAGGA CAAGTTAATGTGGAG TGACCAGCAGCTGGC AAGGGGAAGGAGGAC AAGTTAATGTGGAGC GACCAGCAGCTGGCT AGGGGAAGGAGGACG AGTTAATGTGGAGCT ACCAGCAGCTGGCTA GGGGAAGGAGGACGT GTTAATGTGGAGCTC CCAGCAGCTGGCTAC GGGAAGGAGGACGTG TTAATGTGGAGCTCA CAGCAGCTGGCTACA GGAAGGAGGACGTGC TAATGTGGAGCTCAA AGCAGCTGGCTACAG GAAGGAGGACGTGCA AATGTGGAGCTCAAA GCAGCTGGCTACAGC AAGGAGGACGTGCAC ATGTGGAGCTCAAAT CAGCTGGCTACAGCC AGGAGGACGTGCACT TGTGGAGCTCAAATA AGCTGGCTACAGCCT GGAGGACGTGCACTG GTGGAGCTCAAATAT GCTGGCTACAGCCTC GAGGACGTGCACTGC TGGAGCTCAAATATG CTGGCTACAGCCTCG AGGACGTGCACTGCT GGAGCTCAAATATGC TGGCTACAGCCTCGA GGACGTGCACTGCTA GAGCTCAAATATGCC GGCTACAGCCTCGAT GACGTGCACTGCTAC AGCTCAAATATGCCT GCTACAGCCTCGATT ACGTGCACTGCTACA GCTCAAATATGCCTT CTACAGCCTCGATTT CGTGCACTGCTACAG CTCAAATATGCCTTA TACAGCCTCGATTTA GTGCACTGCTACAGC TCAAATATGCCTTAT ACAGCCTCGATTTAT TGCACTGCTACAGCA CAAATATGCCTTATT CAGCCTCGATTTATA GCACTGCTACAGCAT AAATATGCCTTATTT AGCCTCGATTTATAT CACTGCTACAGCATG AATATGCCTTATTTT GCCTCGATTTATATT ACTGCTACAGCATGC ATATGCCTTATTTTG CCTCGATTTATATTT CTGCTACAGCATGCA TATGCCTTATTTTGC CTCGATTTATATTTC TGCTACAGCATGCAG ATGCCTTATTTTGCA TCGATTTATATTTCT GCTACAGCATGCAGA TGCCTTATTTTGCAC CGATTTATATTTCTG CTACAGCATGCAGAG GCCTTATTTTGCACA GATTTATATTTCTGT TACAGCATGCAGAGC CCTTATTTTGCACAA ATTTATATTTCTGTT ACAGCATGCAGAGCA CTTATTTTGCACAAA TTTATATTTCTGTTT CAGCATGCAGAGCAA TTATTTTGCACAAAA TTATATTTCTGTTTG AGCATGCAGAGCAAG TATTTTGCACAAAAG TATATTTCTGTTTGT GCATGCAGAGCAAGT ATTTTGCACAAAAGA ATATTTCTGTTTGTG CATGCAGAGCAAGTA TTTTGCACAAAAGAC TATTTCTGTTTGTGG ATGCAGAGCAAGTAG TTTGCACAAAAGACT ATTTCTGTTTGTGGT TGCAGAGCAAGTAGA TTGCACAAAAGACTG TTTCTGTTTGTGGTG GCAGAGCAAGTAGAC TGCACAAAAGACTGC TTCTGTTTGTGGTGA CAGAGCAAGTAGACG GCACAAAAGACTGCC TCTGTTTGTGGTGAA AGAGCAAGTAGACGC CACAAAAGACTGCCA CTGTTTGTGGTGAAC GAGCAAGTAGACGCC ACAAAAGACTGCCAA TGTTTGTGGTGAACT AGCAAGTAGACGCCT CAAAAGACTGCCAAG GTTTGTGGTGAACTG GCAAGTAGACGCCTG AAAAGACTGCCAAGG TTTGTGGTGAACTGA CAAGTAGACGCCTGC AAAGACTGCCAAGGA TTGTGGTGAACTGAT AAGTAGACGCCTGCC AAGACTGCCAAGGAC TGTGGTGAACTGATT AGTAGACGCCTGCCG AGACTGCCAAGGACA GTGGTGAACTGATTT GTAGACGCCTGCCGC GACTGCCAAGGACAT TGGTGAACTGATTTT TAGACGCCTGCCGCA ACTGCCAAGGACATG GGTGAACTGATTTTT AGACGCCTGCCGCAA CTGCCAAGGACATGA GTGAACTGATTTTTT GACGCCTGCCGCAAG TGCCAAGGACATGAC TGAACTGATTTTTTT ACGCCTGCCGCAAGT GCCAAGGACATGACC GAACTGATTTTTTTT AACTGATTTTTTTTA CTTTGAATGGTAAAC TTGAATTTTCTTGTC ACTGATTTTTTTTAA TTTGAATGGTAAACT TGAATTTTCTTGTCG CTGATTTTTTTTAAA TTGAATGGTAAACTT GAATTTTCTTGTCGC TGATTTTTTTTAAAC TGAATGGTAAACTTG AATTTTCTTGTCGCT GATTTTTTTTAAACC GAATGGTAAACTTGA ATTTTCTTGTCGCTT ATTTTTTTTAAACCA AATGGTAAACTTGAG TTTTCTTGTCGCTTC TTTTTTTTAAACCAA ATGGTAAACTTGAGC TTTCTTGTCGCTTCC TTTTTTTAAACCAAA TGGTAAACTTGAGCA TTCTTGTCGCTTCCT TTTTTTAAACCAAAG GGTAAACTTGAGCAT TCTTGTCGCTTCCTA TTTTTAAACCAAAGT GTAAACTTGAGCATC CTTGTCGCTTCCTAT TTTTAAACCAAAGTT TAAACTTGAGCATCT TTGTCGCTTCCTATC TTTAAACCAAAGTTT AAACTTGAGCATCTT TGTCGCTTCCTATCA TTAAACCAAAGTTTA AACTTGAGCATCTTT GTCGCTTCCTATCAA TAAACCAAAGTTTAG ACTTGAGCATCTTTT TCGCTTCCTATCAAA AAACCAAAGTTTAGA CTTGAGCATCTTTTC CGCTTCCTATCAAAA AACCAAAGTTTAGAA TTGAGCATCTTTTCA GCTTCCTATCAAAAT ACCAAAGTTTAGAAA TGAGCATCTTTTCAC CTTCCTATCAAAATA CCAAAGTTTAGAAAG GAGCATCTTTTCACT TTCCTATCAAAATAT CAAAGTTTAGAAAGA AGCATCTTTTCACTT TCCTATCAAAATATT AAAGTTTAGAAAGAG GCATCTTTTCACTTT CCTATCAAAATATTC AAGTTTAGAAAGAGG CATCTTTTCACTTTC CTATCAAAATATTCA AGTTTAGAAAGAGGT ATCTTTTCACTTTCC TATCAAAATATTCAG GTTTAGAAAGAGGTT TCTTTTCACTTTCCA ATCAAAATATTCAGA TTTAGAAAGAGGTTT CTTTTCACTTTCCAG TCAAAATATTCAGAG TTAGAAAGAGGTTTT TTTTCACTTTCCAGT CAAAATATTCAGAGA TAGAAAGAGGTTTTT TTTCACTTTCCAGTA AAAATATTCAGAGAC AGAAAGAGGTTTTTG TTCACTTTCCAGTAG AAATATTCAGAGACT GAAAGAGGTTTTTGA TCACTTTCCAGTAGT AATATTCAGAGACTC AAAGAGGTTTTTGAA CACTTTCCAGTAGTC ATATTCAGAGACTCG AAGAGGTTTTTGAAA ACTTTCCAGTAGTCA TATTCAGAGACTCGA AGAGGTTTTTGAAAT CTTTCCAGTAGTCAG ATTCAGAGACTCGAG GAGGTTTTTGAAATG TTTCCAGTAGTCAGC TTCAGAGACTCGAGC AGGTTTTTGAAATGC TTCCAGTAGTCAGCA TCAGAGACTCGAGCA GGTTTTTGAAATGCC TCCAGTAGTCAGCAA CAGAGACTCGAGCAC GTTTTTGAAATGCCT CCAGTAGTCAGCAAA AGAGACTCGAGCACA TTTTTGAAATGCCTA CAGTAGTCAGCAAAG GAGACTCGAGCACAG TTTTGAAATGCCTAT AGTAGTCAGCAAAGA AGACTCGAGCACAGC TTTGAAATGCCTATG GTAGTCAGCAAAGAG GACTCGAGCACAGCA TTGAAATGCCTATGG TAGTCAGCAAAGAGC ACTCGAGCACAGCAC TGAAATGCCTATGGT AGTCAGCAAAGAGCA CTCGAGCACAGCACC GAAATGCCTATGGTT GTCAGCAAAGAGCAG TCGAGCACAGCACCC AAATGCCTATGGTTT TCAGCAAAGAGCAGT CGAGCACAGCACCCA AATGCCTATGGTTTC CAGCAAAGAGCAGTT GAGCACAGCACCCAG ATGCCTATGGTTTCT AGCAAAGAGCAGTTT AGCACAGCACCCAGA TGCCTATGGTTTCTT GCAAAGAGCAGTTTG GCACAGCACCCAGAC GCCTATGGTTTCTTT CAAAGAGCAGTTTGA CACAGCACCCAGACT CCTATGGTTTCTTTG AAAGAGCAGTTTGAA ACAGCACCCAGACTT CTATGGTTTCTTTGA AAGAGCAGTTTGAAT CAGCACCCAGACTTC TATGGTTTCTTTGAA AGAGCAGTTTGAATT AGCACCCAGACTTCA ATGGTTTCTTTGAAT GAGCAGTTTGAATTT GCACCCAGACTTCAT TGGTTTCTTTGAATG AGCAGTTTGAATTTT CACCCAGACTTCATG GGTTTCTTTGAATGG GCAGTTTGAATTTTC ACCCAGACTTCATGC GTTTCTTTGAATGGT CAGTTTGAATTTTCT CCCAGACTTCATGCG TTTCTTTGAATGGTA AGTTTGAATTTTCTT CCAGACTTCATGCGC TTCTTTGAATGGTAA GTTTGAATTTTCTTG CAGACTTCATGCGCC TCTTTGAATGGTAAA TTTGAATTTTCTTGT AGACTTCATGCGCCC GACTTCATGCGCCCG ACTTTGTGACTTAGG CCCCGTACAGTGCGC ACTTCATGCGCCCGT CTTTGTGACTTAGGC CCCGTACAGTGCGCA CTTCATGCGCCCGTG TTTGTGACTTAGGCG CCGTACAGTGCGCAC TTCATGCGCCCGTGG TTGTGACTTAGGCGG CGTACAGTGCGCACA TCATGCGCCCGTGGA TGTGACTTAGGCGGC GTACAGTGCGCACAG CATGCGCCCGTGGAA GTGACTTAGGCGGCT TACAGTGCGCACAGG ATGCGCCCGTGGAAT TGACTTAGGCGGCTG ACAGTGCGCACAGGC TGCGCCCGTGGAATG GACTTAGGCGGCTGT CAGTGCGCACAGGCT GCGCCCGTGGAATGC ACTTAGGCGGCTGTG AGTGCGCACAGGCTT CGCCCGTGGAATGCT CTTAGGCGGCTGTGT GTGCGCACAGGCTTT GCCCGTGGAATGCTC TTAGGCGGCTGTGTT TGCGCACAGGCTTTA CCCGTGGAATGCTCA TAGGCGGCTGTGTTG GCGCACAGGCTTTAT CCGTGGAATGCTCAC AGGCGGCTGTGTTGC CGCACAGGCTTTATC CGTGGAATGCTCACC GGCGGCTGTGTTGCC GCACAGGCTTTATCG GTGGAATGCTCACCA GCGGCTGTGTTGCCT CACAGGCTTTATCGA TGGAATGCTCACCAC CGGCTGTGTTGCCTA ACAGGCTTTATCGAG GGAATGCTCACCACA GGCTGTGTTGCCTAT CAGGCTTTATCGAGA GAATGCTCACCACAT GCTGTGTTGCCTATG AGGCTTTATCGAGAA AATGCTCACCACATG CTGTGTTGCCTATGT GGCTTTATCGAGAAT ATGCTCACCACATGT TGTGTTGCCTATGTA GCTTTATCGAGAATA TGCTCACCACATGTT GTGTTGCCTATGTAG CTTTATCGAGAATAG GCTCACCACATGTTG TGTTGCCTATGTAGA TTTATCGAGAATAGG CTCACCACATGTTGG GTTGCCTATGTAGAG TTATCGAGAATAGGA TCACCACATGTTGGT TTGCCTATGTAGAGA TATCGAGAATAGGAA CACCACATGTTGGTC TGCCTATGTAGAGAA ATCGAGAATAGGAAA ACCACATGTTGGTCG GCCTATGTAGAGAAC TCGAGAATAGGAAAA CCACATGTTGGTCGA CCTATGTAGAGAACA CGAGAATAGGAAAAC CACATGTTGGTCGAA CTATGTAGAGAACAC GAGAATAGGAAAACC ACATGTTGGTCGAAG TATGTAGAGAACACG AGAATAGGAAAACCT CATGTTGGTCGAAGC ATGTAGAGAACACGC GAATAGGAAAACCTT ATGTTGGTCGAAGCG TGTAGAGAACACGCT AATAGGAAAACCTTT TGTTGGTCGAAGCGG GTAGAGAACACGCTT ATAGGAAAACCTTTA GTTGGTCGAAGCGGC TAGAGAACACGCTTC TAGGAAAACCTTTAA TTGGTCGAAGCGGCC AGAGAACACGCTTCA AGGAAAACCTTTAAA TGGTCGAAGCGGCCG GAGAACACGCTTCAC GGAAAACCTTTAAAC GGTCGAAGCGGCCGA AGAACACGCTTCACC GAAAACCTTTAAACC GTCGAAGCGGCCGAC GAACACGCTTCACCC AAAACCTTTAAACCC TCGAAGCGGCCGACC AACACGCTTCACCCC AAACCTTTAAACCCC CGAAGCGGCCGACCA ACACGCTTCACCCCC AACCTTTAAACCCCG GAAGCGGCCGACCAC CACGCTTCACCCCCA ACCTTTAAACCCCGG AAGCGGCCGACCACT ACGCTTCACCCCCAC CCTTTAAACCCCGGT AGCGGCCGACCACTG CGCTTCACCCCCACT CTTTAAACCCCGGTC GCGGCCGACCACTGA GCTTCACCCCCACTC TTTAAACCCCGGTCA CGGCCGACCACTGAC CTTCACCCCCACTCC TTAAACCCCGGTCAT GGCCGACCACTGACT TTCACCCCCACTCCC TAAACCCCGGTCATC GCCGACCACTGACTT TCACCCCCACTCCCC AAACCCCGGTCATCC CCGACCACTGACTTT CACCCCCACTCCCCG AACCCCGGTCATCCG CGACCACTGACTTTG ACCCCCACTCCCCGT ACCCCGGTCATCCGG GACCACTGACTTTGT CCCCCACTCCCCGTA CCCCGGTCATCCGGA ACCACTGACTTTGTG CCCCACTCCCCGTAC CCCGGTCATCCGGAC CCACTGACTTTGTGA CCCACTCCCCGTACA CCGGTCATCCGGACA CACTGACTTTGTGAC CCACTCCCCGTACAG CGGTCATCCGGACAT ACTGACTTTGTGACT CACTCCCCGTACAGT GGTCATCCGGACATC CTGACTTTGTGACTT ACTCCCCGTACAGTG GTCATCCGGACATCC TGACTTTGTGACTTA CTCCCCGTACAGTGC TCATCCGGACATCCC GACTTTGTGACTTAG TCCCCGTACAGTGCG CATCCGGACATCCCA ATCCGGACATCCCAA TGAAACAAGGGCGTG TGTACTGCTTGGGGA TCCGGACATCCCAAC GAAACAAGGGCGTGG GTACTGCTTGGGGAC CCGGACATCCCAACG AAACAAGGGCGTGGA TACTGCTTGGGGACT CGGACATCCCAACGC AACAAGGGCGTGGAT ACTGCTTGGGGACTA GGACATCCCAACGCA ACAAGGGCGTGGATC CTGCTTGGGGACTAT GACATCCCAACGCAT CAAGGGCGTGGATCC TGCTTGGGGACTATT ACATCCCAACGCATG AAGGGCGTGGATCCC GCTTGGGGACTATTG CATCCCAACGCATGC AGGGCGTGGATCCCT CTTGGGGACTATTGG ATCCCAACGCATGCT GGGCGTGGATCCCTC TTGGGGACTATTGGA TCCCAACGCATGCTC GGCGTGGATCCCTCA TGGGGACTATTGGAG CCCAACGCATGCTCC GCGTGGATCCCTCAA GGGGACTATTGGAGA CCAACGCATGCTCCT CGTGGATCCCTCAAC GGGACTATTGGAGAA CAACGCATGCTCCTG GTGGATCCCTCAACC GGACTATTGGAGAAA AACGCATGCTCCTGG TGGATCCCTCAACCA GACTATTGGAGAAAA ACGCATGCTCCTGGA GGATCCCTCAACCAA ACTATTGGAGAAAAT CGCATGCTCCTGGAG GATCCCTCAACCAAG CTATTGGAGAAAATA GCATGCTCCTGGAGC ATCCCTCAACCAAGA TATTGGAGAAAATAA CATGCTCCTGGAGCT TCCCTCAACCAAGAA ATTGGAGAAAATAAG ATGCTCCTGGAGCTC CCCTCAACCAAGAAG TTGGAGAAAATAAGG TGCTCCTGGAGCTCA CCTCAACCAAGAAGA TGGAGAAAATAAGGT GCTCCTGGAGCTCAC CTCAACCAAGAAGAA GGAGAAAATAAGGTG CTCCTGGAGCTCACA TCAACCAAGAAGAAT GAGAAAATAAGGTGG TCCTGGAGCTCACAG CAACCAAGAAGAATG AGAAAATAAGGTGGA CCTGGAGCTCACAGC AACCAAGAAGAATGT GAAAATAAGGTGGAG CTGGAGCTCACAGCC ACCAAGAAGAATGTT AAAATAAGGTGGAGT TGGAGCTCACAGCCT CCAAGAAGAATGTTT AAATAAGGTGGAGTC GGAGCTCACAGCCTT CAAGAAGAATGTTTA AATAAGGTGGAGTCC GAGCTCACAGCCTTC AAGAAGAATGTTTAT ATAAGGTGGAGTCCT AGCTCACAGCCTTCT AGAAGAATGTTTATG TAAGGTGGAGTCCTA GCTCACAGCCTTCTG GAAGAATGTTTATGT AAGGTGGAGTCCTAC CTCACAGCCTTCTGT AAGAATGTTTATGTC AGGTGGAGTCCTACT TCACAGCCTTCTGTG AGAATGTTTATGTCT GGTGGAGTCCTACTT CACAGCCTTCTGTGG GAATGTTTATGTCTT GTGGAGTCCTACTTG ACAGCCTTCTGTGGT AATGTTTATGTCTTC TGGAGTCCTACTTGT CAGCCTTCTGTGGTG ATGTTTATGTCTTCA GGAGTCCTACTTGTT AGCCTTCTGTGGTGT TGTTTATGTCTTCAA GAGTCCTACTTGTTT GCCTTCTGTGGTGTC GTTTATGTCTTCAAG AGTCCTACTTGTTTA CCTTCTGTGGTGTCA TTTATGTCTTCAAGT GTCCTACTTGTTTAA CTTCTGTGGTGTCAT TTATGTCTTCAAGTG TCCTACTTGTTTAAA TTCTGTGGTGTCATT TATGTCTTCAAGTGA CCTACTTGTTTAAAA TCTGTGGTGTCATTT ATGTCTTCAAGTGAC CTACTTGTTTAAAAA CTGTGGTGTCATTTC TGTCTTCAAGTGACC TACTTGTTTAAAAAA TGTGGTGTCATTTCT GTCTTCAAGTGACCT ACTTGTTTAAAAAAT GTGGTGTCATTTCTG TCTTCAAGTGACCTG CTTGTTTAAAAAATA TGGTGTCATTTCTGA CTTCAAGTGACCTGT TTGTTTAAAAAATAT GGTGTCATTTCTGAA TTCAAGTGACCTGTA TGTTTAAAAAATATG GTGTCATTTCTGAAA TCAAGTGACCTGTAC GTTTAAAAAATATGT TGTCATTTCTGAAAC CAAGTGACCTGTACT TTTAAAAAATATGTA GTCATTTCTGAAACA AAGTGACCTGTACTG TTAAAAAATATGTAT TCATTTCTGAAACAA AGTGACCTGTACTGC TAAAAAATATGTATC CATTTCTGAAACAAG GTGACCTGTACTGCT AAAAAATATGTATCT ATTTCTGAAACAAGG TGACCTGTACTGCTT AAAAATATGTATCTA TTTCTGAAACAAGGG GACCTGTACTGCTTG AAAATATGTATCTAA TTCTGAAACAAGGGC ACCTGTACTGCTTGG AAATATGTATCTAAG TCTGAAACAAGGGCG CCTGTACTGCTTGGG AATATGTATCTAAGA CTGAAACAAGGGCGT CTGTACTGCTTGGGG ATATGTATCTAAGAA TATGTATCTAAGAAT GGCCCTCCTCTTCAG GCTTTTGCTGCGGCC ATGTATCTAAGAATG GCCCTCCTCTTCAGG CTTTTGCTGCGGCCC TGTATCTAAGAATGT CCCTCCTCTTCAGGA TTTTGCTGCGGCCCC GTATCTAAGAATGTT CCTCCTCTTCAGGAA TTTGCTGCGGCCCCG TATCTAAGAATGTTC CTCCTCTTCAGGAAT TTGCTGCGGCCCCGT ATCTAAGAATGTTCT TCCTCTTCAGGAATC TGCTGCGGCCCCGTG TCTAAGAATGTTCTA CCTCTTCAGGAATCT GCTGCGGCCCCGTGG CTAAGAATGTTCTAG CTCTTCAGGAATCTT CTGCGGCCCCGTGGG TAAGAATGTTCTAGG TCTTCAGGAATCTTC TGCGGCCCCGTGGGG AAGAATGTTCTAGGG CTTCAGGAATCTTCC GCGGCCCCGTGGGGT AGAATGTTCTAGGGC TTCAGGAATCTTCCT CGGCCCCGTGGGGTA GAATGTTCTAGGGCA TCAGGAATCTTCCTG GGCCCCGTGGGGTAG AATGTTCTAGGGCAC CAGGAATCTTCCTGA GCCCCGTGGGGTAGG ATGTTCTAGGGCACT AGGAATCTTCCTGAA CCCCGTGGGGTAGGA TGTTCTAGGGCACTC GGAATCTTCCTGAAG CCCGTGGGGTAGGAG GTTCTAGGGCACTCT GAATCTTCCTGAAGA CCGTGGGGTAGGAGG TTCTAGGGCACTCTG AATCTTCCTGAAGAC CGTGGGGTAGGAGGG TCTAGGGCACTCTGG ATCTTCCTGAAGACA GTGGGGTAGGAGGGA CTAGGGCACTCTGGG TCTTCCTGAAGACAT TGGGGTAGGAGGGAC TAGGGCACTCTGGGA CTTCCTGAAGACATG GGGGTAGGAGGGACA AGGGCACTCTGGGAA TTCCTGAAGACATGG GGGTAGGAGGGACAG GGGCACTCTGGGAAC TCCTGAAGACATGGC GGTAGGAGGGACAGA GGCACTCTGGGAACC CCTGAAGACATGGCC GTAGGAGGGACAGAG GCACTCTGGGAACCT CTGAAGACATGGCCC TAGGAGGGACAGAGA CACTCTGGGAACCTA TGAAGACATGGCCCA AGGAGGGACAGAGAG ACTCTGGGAACCTAT GAAGACATGGCCCAG GGAGGGACAGAGAGA CTCTGGGAACCTATA AAGACATGGCCCAGT GAGGGACAGAGAGAC TCTGGGAACCTATAA AGACATGGCCCAGTC AGGGACAGAGAGACG CTGGGAACCTATAAA GACATGGCCCAGTCG GGGACAGAGAGACGG TGGGAACCTATAAAG ACATGGCCCAGTCGA GGACAGAGAGACGGG GGGAACCTATAAAGG CATGGCCCAGTCGAA GACAGAGAGACGGGA GGAACCTATAAAGGC ATGGCCCAGTCGAAG ACAGAGAGACGGGAG GAACCTATAAAGGCA TGGCCCAGTCGAAGG CAGAGAGACGGGAGA AACCTATAAAGGCAG GGCCCAGTCGAAGGC AGAGAGACGGGAGAG ACCTATAAAGGCAGG GCCCAGTCGAAGGCC GAGAGACGGGAGAGT CCTATAAAGGCAGGT CCCAGTCGAAGGCCC AGAGACGGGAGAGTC CTATAAAGGCAGGTA CCAGTCGAAGGCCCA GAGACGGGAGAGTCA TATAAAGGCAGGTAT CAGTCGAAGGCCCAG AGACGGGAGAGTCAG ATAAAGGCAGGTATT AGTCGAAGGCCCAGG GACGGGAGAGTCAGC TAAAGGCAGGTATTT GTCGAAGGCCCAGGA ACGGGAGAGTCAGCC AAAGGCAGGTATTTC TCGAAGGCCCAGGAT CGGGAGAGTCAGCCT AAGGCAGGTATTTCG CGAAGGCCCAGGATG GGGAGAGTCAGCCTC AGGCAGGTATTTCGG GAAGGCCCAGGATGG GGAGAGTCAGCCTCC GGCAGGTATTTCGGG AAGGCCCAGGATGGC GAGAGTCAGCCTCCA GCAGGTATTTCGGGC AGGCCCAGGATGGCT AGAGTCAGCCTCCAC CAGGTATTTCGGGCC GGCCCAGGATGGCTT GAGTCAGCCTCCACA AGGTATTTCGGGCCC GCCCAGGATGGCTTT AGTCAGCCTCCACAT GGTATTTCGGGCCCT CCCAGGATGGCTTTT GTCAGCCTCCACATT GTATTTCGGGCCCTC CCAGGATGGCTTTTG TCAGCCTCCACATTC TATTTCGGGCCCTCC CAGGATGGCTTTTGC CAGCCTCCACATTCA ATTTCGGGCCCTCCT AGGATGGCTTTTGCT AGCCTCCACATTCAG TTTCGGGCCCTCCTC GGATGGCTTTTGCTG GCCTCCACATTCAGA TTCGGGCCCTCCTCT GATGGCTTTTGCTGC CCTCCACATTCAGAG TCGGGCCCTCCTCTT ATGGCTTTTGCTGCG CTCCACATTCAGAGG CGGGCCCTCCTCTTC TGGCTTTTGCTGCGG TCCACATTCAGAGGC GGGCCCTCCTCTTCA GGCTTTTGCTGCGGC CCACATTCAGAGGCA CACATTCAGAGGCAT GTGTTTTGTAGTTCA AAGGCAAAGCTTTAT ACATTCAGAGGCATC TGTTTTGTAGTTCAA AGGCAAAGCTTTATT CATTCAGAGGCATCA GTTTTGTAGTTCAAC GGCAAAGCTTTATTT ATTCAGAGGCATCAC TTTTGTAGTTCAACA GCAAAGCTTTATTTT TTCAGAGGCATCACA TTTGTAGTTCAACAA CAAAGCTTTATTTTC TCAGAGGCATCACAA TTGTAGTTCAACAAC AAAGCTTTATTTTCA CAGAGGCATCACAAG TGTAGTTCAACAACT AAGCTTTATTTTCAT AGAGGCATCACAAGT GTAGTTCAACAACTC AGCTTTATTTTCATC GAGGCATCACAAGTA TAGTTCAACAACTCA GCTTTATTTTCATCT AGGCATCACAAGTAA AGTTCAACAACTCAA CTTTATTTTCATCTC GGCATCACAAGTAAT GTTCAACAACTCAAG TTTATTTTCATCTCT GCATCACAAGTAATG TTCAACAACTCAAGA TTATTTTCATCTCTC CATCACAAGTAATGG TCAACAACTCAAGAC TATTTTCATCTCTCA ATCACAAGTAATGGC CAACAACTCAAGACG ATTTTCATCTCTCAT TCACAAGTAATGGCA AACAACTCAAGACGA TTTTCATCTCTCATC CACAAGTAATGGCAC ACAACTCAAGACGAA TTTCATCTCTCATCT ACAAGTAATGGCACA CAACTCAAGACGAAG TTCATCTCTCATCTT CAAGTAATGGCACAA AACTCAAGACGAAGC TCATCTCTCATCTTT AAGTAATGGCACAAT ACTCAAGACGAAGCT CATCTCTCATCTTTT AGTAATGGCACAATT CTCAAGACGAAGCTT ATCTCTCATCTTTTG GTAATGGCACAATTC TCAAGACGAAGCTTA TCTCTCATCTTTTGT TAATGGCACAATTCT CAAGACGAAGCTTAT CTCTCATCTTTTGTC AATGGCACAATTCTT AAGACGAAGCTTATT TCTCATCTTTTGTCC ATGGCACAATTCTTC AGACGAAGCTTATTT CTCATCTTTTGTCCT TGGCACAATTCTTCG GACGAAGCTTATTTC TCATCTTTTGTCCTC GGCACAATTCTTCGG ACGAAGCTTATTTCT CATCTTTTGTCCTCC GCACAATTCTTCGGA CGAAGCTTATTTCTG ATCTTTTGTCCTCCT CACAATTCTTCGGAT GAAGCTTATTTCTGA TCTTTTGTCCTCCTT ACAATTCTTCGGATG AAGCTTATTTCTGAG CTTTTGTCCTCCTTA CAATTCTTCGGATGA AGCTTATTTCTGAGG TTTTGTCCTCCTTAG AATTCTTCGGATGAC GCTTATTTCTGAGGA TTTGTCCTCCTTAGC ATTCTTCGGATGACT CTTATTTCTGAGGAT TTGTCCTCCTTAGCA TTCTTCGGATGACTG TTATTTCTGAGGATA TGTCCTCCTTAGCAC TCTTCGGATGACTGC TATTTCTGAGGATAA GTCCTCCTTAGCACA CTTCGGATGACTGCA ATTTCTGAGGATAAG TCCTCCTTAGCACAA TTCGGATGACTGCAG TTTCTGAGGATAAGC CCTCCTTAGCACAAT TCGGATGACTGCAGA TTCTGAGGATAAGCT CTCCTTAGCACAATG CGGATGACTGCAGAA TCTGAGGATAAGCTC TCCTTAGCACAATGT GGATGACTGCAGAAA CTGAGGATAAGCTCT CCTTAGCACAATGTA GATGACTGCAGAAAA TGAGGATAAGCTCTT CTTAGCACAATGTAA ATGACTGCAGAAAAT GAGGATAAGCTCTTT TTAGCACAATGTAAA TGACTGCAGAAAATA AGGATAAGCTCTTTA TAGCACAATGTAAAA GACTGCAGAAAATAG GGATAAGCTCTTTAA AGCACAATGTAAAAA ACTGCAGAAAATAGT GATAAGCTCTTTAAA GCACAATGTAAAAAA CTGCAGAAAATAGTG ATAAGCTCTTTAAAG CACAATGTAAAAAAG TGCAGAAAATAGTGT TAAGCTCTTTAAAGG ACAATGTAAAAAAGA GCAGAAAATAGTGTT AAGCTCTTTAAAGGC CAATGTAAAAAAGAA CAGAAAATAGTGTTT AGCTCTTTAAAGGCA AATGTAAAAAAGAAT AGAAAATAGTGTTTT GCTCTTTAAAGGCAA ATGTAAAAAAGAATA GAAAATAGTGTTTTG CTCTTTAAAGGCAAA TGTAAAAAAGAATAG AAAATAGTGTTTTGT TCTTTAAAGGCAAAG GTAAAAAAGAATAGT AAATAGTGTTTTGTA CTTTAAAGGCAAAGC TAAAAAAGAATAGTA AATAGTGTTTTGTAG TTTAAAGGCAAAGCT AAAAAAGAATAGTAA ATAGTGTTTTGTAGT TTAAAGGCAAAGCTT AAAAAGAATAGTAAT TAGTGTTTTGTAGTT TAAAGGCAAAGCTTT AAAAGAATAGTAATA AGTGTTTTGTAGTTC AAAGGCAAAGCTTTA AAAGAATAGTAATAT AAGAATAGTAATATC GACACTGGGAGCACA TGCTTTTCTTTATAA AGAATAGTAATATCA ACACTGGGAGCACAT GCTTTTCTTTATAAT GAATAGTAATATCAG CACTGGGAGCACATA CTTTTCTTTATAATT AATAGTAATATCAGA ACTGGGAGCACATAG TTTTCTTTATAATTC ATAGTAATATCAGAA CTGGGAGCACATAGA TTTCTTTATAATTCA TAGTAATATCAGAAC TGGGAGCACATAGAG TTCTTTATAATTCAC AGTAATATCAGAACA GGGAGCACATAGAGA TCTTTATAATTCACA GTAATATCAGAACAG GGAGCACATAGAGAT CTTTATAATTCACAC TAATATCAGAACAGG GAGCACATAGAGATT TTTATAATTCACACA AATATCAGAACAGGA AGCACATAGAGATTC TTATAATTCACACAT ATATCAGAACAGGAA GCACATAGAGATTCA TATAATTCACACATA TATCAGAACAGGAAG CACATAGAGATTCAC ATAATTCACACATAT ATCAGAACAGGAAGG ACATAGAGATTCACC TAATTCACACATATA TCAGAACAGGAAGGA CATAGAGATTCACCC AATTCACACATATAT CAGAACAGGAAGGAG ATAGAGATTCACCCA ATTCACACATATATG AGAACAGGAAGGAGG TAGAGATTCACCCAT TTCACACATATATGC GAACAGGAAGGAGGA AGAGATTCACCCATG TCACACATATATGCA AACAGGAAGGAGGAA GAGATTCACCCATGT CACACATATATGCAG ACAGGAAGGAGGAAT AGATTCACCCATGTT ACACATATATGCAGA CAGGAAGGAGGAATG GATTCACCCATGTTT CACATATATGCAGAG AGGAAGGAGGAATGG ATTCACCCATGTTTG ACATATATGCAGAGA GGAAGGAGGAATGGC TTCACCCATGTTTGT CATATATGCAGAGAA GAAGGAGGAATGGCT TCACCCATGTTTGTT ATATATGCAGAGAAG AAGGAGGAATGGCTT CACCCATGTTTGTTG TATATGCAGAGAAGA AGGAGGAATGGCTTG ACCCATGTTTGTTGA ATATGCAGAGAAGAT GGAGGAATGGCTTGC CCCATGTTTGTTGAA TATGCAGAGAAGATA GAGGAATGGCTTGCT CCATGTTTGTTGAAC ATGCAGAGAAGATAT AGGAATGGCTTGCTG CATGTTTGTTGAACT TGAGAGAAGATATG GGAATGGCTTGCTGG ATGTTTGTTGAACTT GCAGAGAAGATATGT GAATGGCTTGCTGGG TGTTTGTTGAACTTA CAGAGAAGATATGTT AATGGCTTGCTGGGG GTTTGTTGAACTTAG AGAGAAGATATGTTC ATGGCTTGCTGGGGA TTTGTTGAACTTAGA GAGAAGATATGTTCT TGGCTTGCTGGGGAG TTGTTGAACTTAGAG AGAAGATATGTTCTT GGCTTGCTGGGGAGC TGTTGAACTTAGAGT GAAGATATGTTCTTG GCTTGCTGGGGAGCC GTTGAACTTAGAGTC AAGATATGTTCTTGT CTTGCTGGGGAGCCC TTGAACTTAGAGTCA AGATATGTTCTTGTT TTGCTGGGGAGCCCA TGAACTTAGAGTCAT GATATGTTCTTGTTA TGCTGGGGAGCCCAT GAACTTAGAGTCATT ATATGTTCTTGTTAA GCTGGGGAGCCCATC AACTTAGAGTCATTC TATGTTCTTGTTAAC CTGGGGAGCCCATCC ACTTAGAGTCATTCT ATGTTCTTGTTAACA TGGGGAGCCCATCCA CTTAGAGTCATTCTC TGTTCTTGTTAACAT GGGGAGCCCATCCAG TTAGAGTCATTCTCA GTTCTTGTTAACATT GGGAGCCCATCCAGG TAGAGTCATTCTCAT TTCTTGTTAACATTG GGAGCCCATCCAGGA AGAGTCATTCTCATG TCTTGTTAACATTGT GAGCCCATCCAGGAC GAGTCATTCTCATGC CTTGTTAACATTGTA AGCCCATCCAGGACA AGTCATTCTCATGCT TTGTTAACATTGTAT GCCCATCCAGGACAC GTCATTCTCATGCTT TGTTAACATTGTATA CCCATCCAGGACACT TCATTCTCATGCTTT GTTAACATTGTATAC CCATCCAGGACACTG CATTCTCATGCTTTT TTAACATTGTATACA CATCCAGGACACTGG ATTCTCATGCTTTTC TAACATTGTATACAA ATCCAGGACACTGGG TTCTCATGCTTTTCT AACATTGTATACAAC TCCAGGACACTGGGA TCTCATGCTTTTCTT ACATTGTATACAACA CCAGGACACTGGGAG CTCATGCTTTTCTTT CATTGTATACAACAT CAGGACACTGGGAGC TCATGCTTTTCTTTA ATTGTATACAACATA AGGACACTGGGAGCA CATGCTTTTCTTTAT TTGTATACAACATAG GGACACTGGGAGCAC ATGCTTTTCTTTATA TGTATACAACATAGC GTATACAACATAGCC TGTTAGAGATGCTAT CCAGAGACTGGGCTG TATACAACATAGCCC GTTAGAGATGCTATA CAGAGACTGGGCTGC ATACAACATAGCCCC TTAGAGATGCTATAT AGAGACTGGGCTGCT TACAACATAGCCCCA TAGAGATGCTATATG GAGACTGGGCTGCTC ACAACATAGCCCCAA AGAGATGCTATATGA AGACTGGGCTGCTCT CAACATAGCCCCAAA GAGATGCTATATGAT GACTGGGCTGCTCTC AACATAGCCCCAAAT AGATGCTATATGATA ACTGGGCTGCTCTCC ACATAGCCCCAAATA GATGCTATATGATAC CTGGGCTGCTCTCCC CATAGCCCCAAATAT ATGCTATATGATACA TGGGCTGCTCTCCCG ATAGCCCCAAATATA TGCTATATGATACAA GGGCTGCTCTCCCGG TAGCCCCAAATATAG GCTATATGATACAAC GGCTGCTCTCCCGGA AGCCCCAAATATAGT CTATATGATACAACT GCTGCTCTCCCGGAG GCCCCAAATATAGTA TATATGATACAACTG CTGCTCTCCCGGAGG CCCCAAATATAGTAA ATATGATACAACTGT TGCTCTCCCGGAGGC CCCAAATATAGTAAG TATGATACAACTGTG GCTCTCCCGGAGGCC CCAAATATAGTAAGA ATGATACAACTGTGG CTCTCCCGGAGGCCA CAAATATAGTAAGAT TGATACAACTGTGGC TCTCCCGGAGGCCAA AAATATAGTAAGATC GATACAACTGTGGCC CTCCCGGAGGCCAAA AATATAGTAAGATCT ATACAACTGTGGCCA TCCCGGAGGCCAAAC ATATAGTAAGATCTA TACAACTGTGGCCAT CCCGGAGGCCAAACC TATAGTAAGATCTAT ACAACTGTGGCCATG CCGGAGGCCAAACCC ATAGTAAGATCTATA CAACTGTGGCCATGA CGGAGGCCAAACCCA TAGTAAGATCTATAC AACTGTGGCCATGAC GGAGGCCAAACCCAA AGTAAGATCTATACT ACTGTGGCCATGACT GAGGCCAAACCCAAG GTAAGATCTATACTA CTGTGGCCATGACTG AGGCCAAACCCAAGA TAAGATCTATACTAG TGTGGCCATGACTGA GGCCAAACCCAAGAA AAGATCTATACTAGA GTGGCCATGACTGAG GCCAAACCCAAGAAG AGATCTATACTAGAT TGGCCATGACTGAGG CCAAACCCAAGAAGG GATCTATACTAGATA GGCCATGACTGAGGA CAAACCCAAGAAGGT ATCTATACTAGATAA GCCATGACTGAGGAA AAACCCAAGAAGGTC TCTATACTAGATAAT CCATGACTGAGGAAA AACCCAAGAAGGTCT CTATACTAGATAATC CATGACTGAGGAAAG ACCCAAGAAGGTCTG TATACTAGATAATCC ATGACTGAGGAAAGG CCCAAGAAGGTCTGG ATACTAGATAATCCT TGACTGAGGAAAGGA CCAAGAAGGTCTGGC TACTAGATAATCCTA GACTGAGGAAAGGAG CAAGAAGGTCTGGCA ACTAGATAATCCTAG ACTGAGGAAAGGAGC AAGAAGGTCTGGCAA CTAGATAATCCTAGA CTGAGGAAAGGAGCT AGAAGGTCTGGCAAA TAGATAATCCTAGAT TGAGGAAAGGAGCTC GAAGGTCTGGCAAAG AGATAATCCTAGATG GAGGAAAGGAGCTCA AAGGTCTGGCAAAGT GATAATCCTAGATGA AGGAAAGGAGCTCAC AGGTCTGGCAAAGTC ATAATCCTAGATGAA GGAAAGGAGCTCACG GGTCTGGCAAAGTCA TAATCCTAGATGAAA GAAAGGAGCTCACGC GTCTGGCAAAGTCAG AATCCTAGATGAAAT AAAGGAGCTCACGCC TCTGGCAAAGTCAGG ATCCTAGATGAAATG AAGGAGCTCACGCCC CTGGCAAAGTCAGGC TCCTAGATGAAATGT AGGAGCTCACGCCCA TGGCAAAGTCAGGCT CCTAGATGAAATGTT GGAGCTCACGCCCAG GGCAAAGTCAGGCTC CTAGATGAAATGTTA GAGCTCACGCCCAGA GCAAAGTCAGGCTCA TAGATGAAATGTTAG AGCTCACGCCCAGAG CAAAGTCAGGCTCAG AGATGAAATGTTAGA GCTCACGCCCAGAGA AAAGTCAGGCTCAGG GATGAAATGTTAGAG CTCACGCCCAGAGAC AAGTCAGGCTCAGGG ATGAAATGTTAGAGA TCACGCCCAGAGACT AGTCAGGCTCAGGGA TGAAATGTTAGAGAT CACGCCCAGAGACTG GTCAGGCTCAGGGAG GAAATGTTAGAGATG ACGCCCAGAGACTGG TCAGGCTCAGGGAGA AAATGTTAGAGATGC CGCCCAGAGACTGGG CAGGCTCAGGGAGAC AATGTTAGAGATGCT GCCCAGAGACTGGGC AGGCTCAGGGAGACT ATGTTAGAGATGCTA CCCAGAGACTGGGCT GGCTCAGGGAGACTC GCTCAGGGAGACTCT CTCTCCTTGAAAACA TATTTTTTTAACTTT CTCAGGGAGACTCTG TCTCCTTGAAAACAG ATTTTTTTAACTTTT TCAGGGAGACTCTGC CTCCTTGAAAACAGA TTTTTTTAACTTTTT CAGGGAGACTCTGCC TCCTTGAAAACAGAG TTTTTTAACTTTTTG AGGGAGACTCTGCCC CCTTGAAAACAGAGG TTTTTAACTTTTTGG GGGAGACTCTGCCCT CTTGAAAACAGAGGG TTTTAACTTTTTGGG GGAGACTCTGCCCTG TTGAAAACAGAGGGG TTTAACTTTTTGGGG GAGACTCTGCCCTGC TGAAAACAGAGGGGT TTAACTTTTTGGGGG AGACTCTGCCCTGCT GAAAACAGAGGGGTC TAACTTTTTGGGGGG GACTCTGCCCTGCTG AAAACAGAGGGGTCT AACTTTTTGGGGGGA ACTCTGCCCTGCTGC AAACAGAGGGGTCTC ACTTTTTGGGGGGAA CTCTGCCCTGCTGCA AACAGAGGGGTCTCA CTTTTTGGGGGGAAA TCTGCCCTGCTGCAG ACAGAGGGGTCTCAA TTTTTGGGGGGAAAA CTGCCCTGCTGCAGA CAGAGGGGTCTCAAG TTTTGGGGGGAAAAG TGCCCTGCTGCAGAC AGAGGGGTCTCAAGA TTTGGGGGGAAAAGT GCCCTGCTGCAGACC GAGGGGTCTCAAGAC TTGGGGGGAAAAGTA CCCTGCTGCAGACCT AGGGGTCTCAAGACA TGGGGGGAAAAGTAT CCTGCTGCAGACCTC GGGGTCTCAAGACAT GGGGGGAAAAGTATT CTGCTGCAGACCTCG GGGTCTCAAGACATT GGGGGAAAAGTATTT TGCTGCAGACCTCGG GGTCTCAAGACATTC GGGGAAAAGTATTTT GCTGCAGACCTCGGT GTCTCAAGACATTCT GGGAAAAGTATTTTT CTGCAGACCTCGGTG TCTCAAGACATTCTG GGAAAAGTATTTTTG TGCAGACCTCGGTGT CTCAAGACATTCTGC GAAAAGTATTTTTGA GCAGACCTCGGTGTG TCAAGACATTCTGCC AAAAGTATTTTTGAG CAGACCTCGGTGTGG CAAGACATTCTGCCT AAAGTATTTTTGAGA AGACCTCGGTGTGGA AAGACATTCTGCCTA AAGTATTTTTGAGAA GACCTCGGTGTGGAC AGACATTCTGCCTAC AGTATTTTTGAGAAG ACCTCGGTGTGGACA GACATTCTGCCTACC GTATTTTTGAGAAGT CCTCGGTGTGGACAC ACATTCTGCCTACCT TATTTTTGAGAAGTT CTCGGTGTGGACACA CATTCTGCCTACCTA ATTTTTGAGAAGTTT TCGGTGTGGACACAC ATTCTGCCTACCTAT TTTTTGAGAAGTTTG CGGTGTGGACACACG TTCTGCCTACCTATT TTTTGAGAAGTTTGT GGTGTGGACACACGC TCTGCCTACCTATTA TTTGAGAAGTTTGTC GTGTGGACACACGCT CTGCCTACCTATTAG TTGAGAAGTTTGTCT TGTGGACACACGCTG TGCCTACCTATTAGC TGAGAAGTTTGTCTT GTGGACACACGCTGC GCCTACCTATTAGCT GAGAAGTTTGTCTTG TGGACACACGCTGCA CCTACCTATTAGCTT AGAAGTTTGTCTTGC GGACACACGCTGCAT CTACCTATTAGCTTT GAAGTTTGTCTTGCA GACACACGCTGCATA TACCTATTAGCTTTT AAGTTTGTCTTGCAA ACACACGCTGCATAG ACCTATTAGCTTTTC AGTTTGTCTTGCAAT CACACGCTGCATAGA CCTATTAGCTTTTCT GTTTGTCTTGCAATG ACACGCTGCATAGAG CTATTAGCTTTTCTT TTTGTCTTGCAATGT CACGCTGCATAGAGC TATTAGCTTTTCTTT TTGTCTTGCAATGTA ACGCTGCATAGAGCT ATTAGCTTTTCTTTA TGTCTTGCAATGTAT CGCTGCATAGAGCTC TTAGCTTTTCTTTAT GTCTTGCAATGTATT GCTGCATAGAGCTCT TAGCTTTTCTTTATT TCTTGCAATGTATTT CTGCATAGAGCTCTC AGCTTTTCTTTATTT CTTGCAATGTATTTA TGCATAGAGCTCTCC GCTTTTCTTTATTTT TTGCAATGTATTTAT GCATAGAGCTCTCCT CTTTTCTTTATTTTT TGCAATGTATTTATA CATAGAGCTCTCCTT TTTTCTTTATTTTTT GCAATGTATTTATAA ATAGAGCTCTCCTTG TTTCTTTATTTTTTT CAATGTATTTATAAA TAGAGCTCTCCTTGA TTCTTTATTTTTTTA AATGTATTTATAAAT AGAGCTCTCCTTGAA TCTTTATTTTTTTAA ATGTATTTATAAATA GAGCTCTCCTTGAAA CTTTATTTTTTTAAC TGTATTTATAAATAG AGCTCTCCTTGAAAA TTTATTTTTTTAACT GTATTTATAAATAGT GCTCTCCTTGAAAAC TTATTTTTTTAACTT TATTTATAAATAGTA ATTTATAAATAGTAA TTTATAAATAGTAAA TTATAAATAGTAAAT TATAAATAGTAAATA ATAAATAGTAAATAA TAAATAGTAAATAAA AAATAGTAAATAAAG AATAGTAAATAAAGT ATAGTAAATAAAGTT TAGTAAATAAAGTTT AGTAAATAAAGTTTT GTAAATAAAGTTTTT TAAATAAAGTTTTTA AAATAAAGTTTTTAC AATAAAGTTTTTACC ATAAAGTTTTTACCA TAAAGTTTTTACCAT AAAGTTTTTACCATT
EXAMPLE 8 Antisense Oligonucleotides of IGF-I Receptor[0058] Antisense oligonucleotides to IGF-I may selected from molecules capable of interacting with one or the following sense oligonucleotides: 6 TTTTTTTTTTTTTTG TCATCCCAAATAAAA GGCTCCGGAGGAGGG TTTTTTTTTTTTTGA CATCCCAAATAAAAG GCTCCGGAGGAGGGT TTTTTTTTTTTTGAG ATCCCAAATAAAAGG CTCCGGAGGAGGGTC TTTTTTTTTTTGAGA TCCCAAATAAAAGGA TCCGGAGGAGGGTCC TTTTTTTTTTGAGAA CCCAAATAAAAGGAA CCGGAGGAGGGTCCC TTTTTTTTTGAGAAA CCAAATAAAAGGAAT CGGAGGAGGGTCCCC TTTTTTTTGAGAAAG CAAATAAAAGGAATG GGAGGAGGGTCCCCG TTTTTTTGAGAAAGG AAATAAAAGGAATGA GAGGAGGGTCCCCGA TTTTTTGAGAAAGGG AATAAAAGGAATGAA AGGAGGGTCCCCGAC TTTTTGAGAAAGGGA ATAAAAGGAATGAAG GGAGGGTCCCCGACC TTTTGAGAAAGGGAA TAAAAGGAATGAAGT GAGGGTCCCCGACCT TTTGAGAAAGGGAAT AAAAGGAATGAAGTC AGGGTCCCCGACCTC TTGAGAAAGGGAATT AAAGGAATGAAGTCT GGGTCCCCGACCTCG TGAGAAAGGGAATTT AAGGAATGAAGTCTG GGTCCCCGACCTCGC GAGAAAGGGAATTTC AGGAATGAAGTCTGG GTCCCCGACCTCGCT AGAAAGGGAATTTCA GGAATGAAGTCTGGC TCCCCGACCTCGCTG GAAAGGGAATTTCAT GAATGAAGTCTGGCT CCCCGACCTCGCTGT AAAGGGAATTTCATC AATGAAGTCTGGCTC CCCGACCTCGCTGTG AAGGGAATTTCATCC ATGAAGTCTGGCTCC CCGACCTCGCTGTGG AGGGAATTTCATCCC TGAAGTCTGGCTCCG CGACCTCGCTGTGGG GGGAATTTCATCCCA GAAGTCTGGCTCCGG GACCTCGCTGTGGGG GGAATTTCATCCCAA AAGTCTGGCTCCGGA ACCTCGCTGTGGGGG GAATTTCATCCCAAA AGTCTGGCTCCGGAG CCTCGCTGTGGGGGC AATTTCATCCCAAAT GTCTGGCTCCGGAGG CTCGCTGTGGGGGCT ATTTCATCCCAAATA TCTGGCTCCGGAGGA TCGCTGTGGGGGCTC TTTCATCCCAAATAA CTGGCTCCGGAGGAG CGCTGTGGGGGCTCC TTCATCCCAAATAAA TGGCTCCGGAGGAGG GCTGTGGGGGCTCCT CTGTGGGGGCTCCTG AATCTGCGGGCCAGG AGAACTGCACGGTGA TGTGGGGGCTCCTGT ATCTGCGGGCCAGGC GAACTGCACGGTGAT GTGGGGGCTCCTGTT TCTGCGGGCCAGGCA AACTGCACGGTGATC TGGGGGCTCCTGTTT CTGCGGGCCAGGCAT ACTGCACGGTGATCG GGGGGCTCCTGTTTC TGCGGGCCAGGCATC CTGCACGGTGATCGA GGGGCTCCTGTTTCT GCGGGCCAGGCATCG TGCACGGTGATCGAG GGGCTCCTGTTTCTC CGGGCCAGGCATCGA GCACGGTGATCGAGG GGCTCCTGTTTCTCT GGGCCAGGCATCGAC CACGGTGATCGAGGG GCTCCTGTTTCTCTC GGCCAGGCATCGACA ACGGTGATCGAGGGC CTCCTGTTTCTCTCC GCCAGGCATCGACAT CGGTGATCGAGGGCT TCCTGTTTCTCTCCG CCAGGCATCGACATC GGTGATCGAGGGCTA CCTGTTTCTCTCCGC CAGGCATCGACATCC GTGATCGAGGGCTAC CTGTTTCTCTCCGCC AGGCATCGACATCCG TGATCGAGGGCTACC TGTTTCTCTCCGCCG GGCATCGACATCCGC GATCGAGGGCTACCT GTTTCTCTCCGCCGC GCATCGACATCCGCA ATCGAGGGCTACCTC TTTCTCTCCGCCGCG CATCGACATCCGCAA TCGAGGGCTACCTCC TTCTCTCCGCCGCGC ATCGACATCCGCAAC CGAGGGCTACCTCCA TCTCTCCGCCGCGCT TCGACATCCGCAACG GAGGGCTACCTCCAC CTCTCCGCCGCGCTC CGACATCCGCAACGA AGGGCTACCTCCACA TCTCCGCCGCGCTCT GACATCCGCAACGAC GGGCTACCTCCACAT CTCCGCCGCGCTCTC ACATCCGCAACGACT GGCTACCTCCACATC TCCGCCGCGCTCTCG CATCCGCAACGACTA GCTACCTCCACATCC CCGCCGCGCTCTCGC ATCCGCAACGACTAT CTACCTCCACATCCT CGCCGCGCTCTCGCT TCCGCAACGACTATC TACCTCCACATCCTG GCCGCGCTCTCGCTC CCGCAACGACTATCA ACCTCCACATCCTGC CCGCGCTCTCGCTCT CGCAACGACTATCAG CCTCCACATCCTGCT CGCGCTCTCGCTCTG GCAACGACTATCAGC CTCCACATCCTGCTC GCGCTCTCGCTCTGG CAACGACTATCAGCA TCCACATCCTGCTCA CGCTCTCGCTCTGGC AACGACTATCAGCAG CCACATCCTGCTCAT GCTCTCGCTCTGGCC ACGACTATCAGCAGC CACATCCTGCTCATC CTCTCGCTCTGGCCG CGACTATCAGCAGCT ACATCCTGCTCATCT TCTCGCTCTGGCCGA GACTATCAGCAGCTG CATCCTGCTCATCTC CTCGCTCTGGCCGAC ACTATCAGCAGCTGA ATCCTGCTCATCTCC TCGCTCTGGCCGACG CTATCAGCAGCTGAA TCCTGCTCATCTCCA CGCTCTGGCCGACGA TATCAGCAGCTGAAG CCTGCTCATCTCCAA GCTCTGGCCGACGAG ATCAGCAGCTGAAGC CTGCTCATCTCCAAG CTCTGGCCGACGAGT TCAGCAGCTGAAGCG TGCTCATCTCCAAGG TCTGGCCGACGAGTG CAGCAGCTGAAGCGC GCTCATCTCCAAGGC CTGGCCGACGAGTGG AGCAGCTGAAGCGCC CTCATCTCCAAGGCC TGGCCGACGAGTGGA GCAGCTGAAGCGCCT TCATCTCCAAGGCCG GGCCGACGAGTGGAG CAGCTGAAGCGCCTG CATCTCCAAGGCCGA GCCGACGAGTGGAGA AGCTGAAGCGCCTGG ATCTCCAAGGCCGAG CCGACGAGTGGAGAA GCTGAAGCGCCTGGA TCTCCAAGGCCGAGG CGACGAGTGGAGAAA CTGAAGCGCCTGGAG CTCCAAGGCCGAGGA GACGAGTGGAGAAAT TGAAGCGCCTGGAGA TCCAAGGCCGAGGAC ACGAGTGGAGAAATC GAAGCGCCTGGAGAA CCAAGGCCGAGGACT CGAGTGGAGAAATCT AAGCGCCTGGAGAAC CAAGGCCGAGGACTA GAGTGGAGAAATCTG AGCGCCTGGAGAACT AAGGCCGAGGACTAC AGTGGAGAAATCTGC GCGCCTGGAGAACTG AGGCCGAGGACTACC GTGGAGAAATCTGCG CGCCTGGAGAACTGC GGCCGAGGACTACCG TGGAGAAATCTGCGG GCCTGGAGAACTGCA GCCGAGGACTACCGC GGAGAAATCTGCGGG CCTGGAGAACTGCAC CCGAGGACTACCGCA GAGAAATCTGCGGGC CTGGAGAACTGCACG CGAGGACTACCGCAG AGAAATCTGCGGGCC TGGAGAACTGCACGG GAGGACTACCGCAGC GAAATCTGCGGGCCA GGAGAACTGCACGGT AGGACTACCGCAGCT AAATCTGCGGGCCAG GAGAACTGCACGGTG GGACTACCGCAGCTA GACTACCGCAGCTAC GTTCCGAGTGGCTGG TCCGCGGCTGGAAAC ACTACCGCAGCTACC TTCCGAGTGGCTGGC CCGCGGCTGGAAACT CTACCGCAGCTACCG TCCGAGTGGCTGGCC CGCGGCTGGAAACTC TACCGCAGCTACCGC CCGAGTGGCTGGCCT GCGGCTGGAAACTCT ACCGCAGCTACCGCT CGAGTGGCTGGCCTC CGGCTGGAAACTCTT CCGCAGCTACCGCTT GAGTGGCTGGCCTCG GGCTGGAAACTCTTC CGCAGCTACCGCTTC AGTGGCTGGCCTCGA GCTGGAAACTCTTCT GCAGCTACCGCTTCC GTGGCTGGCCTCGAG CTGGAAACTCTTCTA CAGCTACCGCTTCCC TGGCTGGCCTCGAGA TGGAAACTCTTCTAC AGCTACCGCTTCCCC GGCTGGCCTCGAGAG GGAAACTCTTCTACA GCTACCGCTTCCCCA GCTGGCCTCGAGAGC GAAACTCTTCTACAA CTACCGCTTCCCCAA CTGGCCTCGAGAGCC AAACTCTTCTACAAC TACCGCTTCCCCAAG TGGCCTCGAGAGCCT AACTCTTCTACAACT ACCGCTTCCCCAAGC GGCCTCGAGAGCCTC ACTCTTCTACAACTA CCGCTTCCCCAAGCT GCCTCGAGAGCCTCG CTCTTCTACAACTAC CGCTTCCCCAAGCTC CCTCGAGAGCCTCGG TCTTCTACAACTACG GCTTCCCCAAGCTCA CTCGAGAGCCTCGGA CTTCTACAACTACGC CTTCCCCAAGCTCAC TCGAGAGCCTCGGAG TTCTACAACTACGCC TTCCCCAAGCTCACG CGAGAGCCTCGGAGA TCTACAACTACGCCC TCCCCAAGCTCACGG GAGAGCCTCGGAGAC CTACAACTACGCCCT CCCCAAGCTCACGGT AGAGCCTCGGAGACC TACAACTACGCCCTG CCCAAGCTCACGGTC GAGCCTCGGAGACCT ACAACTACGCCCTGG CCAAGCTCACGGTCA AGCCTCGGAGACCTC CAACTACGCCCTGGT CAAGCTCACGGTCAT GCCTCGGAGACCTCT AACTACGCCCTGGTC AAGCTCACGGTCATT CCTCGGAGACCTCTT ACTACGCCCTGGTCA AGCTCACGGTCATTA CTCGGAGACCTCTTC CTACGCCCTGGTCAT GCTCACGGTCATTAC TCGGAGACCTCTTCC TACGCCCTGGTCATC CTCACGGTCATTACC CGGAGACCTCTTCCC ACGCCCTGGTCATCT TCACGGTCATTACCG GGAGACCTCTTCCCC CGCCCTGGTCATCTT CACGGTCATTACCGA GAGACCTCTTCCCCA GCCCTGGTCATCTTC ACGGTCATTACCGAG AGACCTCTTCCCCAA CCCTGGTCATCTTCG CGGTCATTACCGAGT GACCTCTTCCCCAAC CCTGGTCATCTTCGA GGTCATTACCGAGTA ACCTCTTCCCCAACC CTGGTCATCTTCGAG GTCATTACCGAGTAC CCTCTTCCCCAACCT TGGTCATCTTCGAGA TCATTACCGAGTACT CTCTTCCCCAACCTC GGTCATCTTCGAGAT CATTACCGAGTACTT TCTTCCCCAACCTCA GTCATCTTCGAGATG ATTACCGAGTACTTG CTTCCCCAACCTCAC TCATCTTCGAGATGA TTACCGAGTACTTGC TTCCCCAACCTCACG CATCTTCGAGATGAC TACCGAGTACTTGCT TCCCCAACCTCACGG ATCTTCGAGATGACC ACCGAGTACTTGCTG CCCCAACCTCACGGT TCTTCGAGATGACCA CCGAGTACTTGCTGC CCCAACCTCACGGTC CTTCGAGATGACCAA CGAGTACTTGCTGCT CCAACCTCACGGTCA TTCGAGATGACCAAT GAGTACTTGCTGCTG CAACCTCACGGTCAT TCGAGATGACCAATC AGTACTTGCTGCTGT AACCTCACGGTCATC CGAGATGACCAATCT GTACTTGCTGCTGTT ACCTCACGGTCATCC GAGATGACCAATCTC TACTTGCTGCTGTTC CCTCACGGTCATCCG AGATGACCAATCTCA ACTTGCTGCTGTTCC CTCACGGTCATCCGC GATGACCAATCTCAA CTTGCTGCTGTTCCG TCACGGTCATCCGCG ATGACCAATCTCAAG TTGCTGCTGTTCCGA CACGGTCATCCGCGG TGACCAATCTCAAGG TGCTGCTGTTCCGAG ACGGTCATCCGCGGC GACCAATCTCAAGGA GCTGCTGTTCCGAGT CGGTCATCCGCGGCT ACCAATCTCAAGGAT CTGCTGTTCCGAGTG GGTCATCCGCGGCTG CCAATCTCAAGGATA TGCTGTTCCGAGTGG GTCATCCGCGGCTGG CAATCTCAAGGATAT GCTGTTCCGAGTGGC TCATCCGCGGCTGGA AATCTCAAGGATATT CTGTTCCGAGTGGCT CATCCGCGGCTGGAA ATCTCAAGGATATTG TGTTCCGAGTGGCTG ATCCGCGGCTGGAAA TCTCAAGGATATTGG CTCAAGGATATTGGG TGAGAAAAATGCTGA ATGCGGTGTCCAATA TCAAGGATATTGGGC GAGAAAAATGCTGAC TGCGGTGTCCAATAA CAAGGATATTGGGCT AGAAAAATGCTGACC GCGGTGTCCAATAAC AAGGATATTGGGCTT GAAAAATGCTGACCT CGGTGTCCAATAACT AGGATATTGGGCTTT AAAAATGCTGACCTC GGTGTCCAATAACTA GGATATTGGGCTTTA AAAATGCTGACCTCT GTGTCCAATAACTAC GATATTGGGCTTTAC AAATGCTGACCTCTG TGTCCAATAACTACA ATATTGGGCTTTACA AATGCTGACCTCTGT GTCCAATAACTACAT TATTGGGCTTTACAA ATGCTGACCTCTGTT TCCAATAACTACATT ATTGGGCTTTACAAC TGCTGACCTCTGTTA CCAATAACTACATTG TTGGGCTTTACAACC GCTGACCTCTGTTAC CAATAACTACATTGT TGGGCTTTACAACCT CTGACCTCTGTTACC AATAACTACATTGTG GGGCTTTACAACCTG TGACCTCTGTTACCT ATAACTACATTGTGG GGCTTTACAACCTGA GACCTCTGTTACCTC TAACTACATTGTGGG GCTTTACAACCTGAG ACCTCTGTTACCTCT AACTACATTGTGGGG CTTTACAACCTGAGG CCTCTGTTACCTCTC ACTACATTGTGGGGA TTTACAACCTGAGGA CTCTGTTACCTCTCC CTACATTGTGGGGAA TTACAACCTGAGGAA TCTGTTACCTCTCCA TACATTGTGGGGAAT TACAACCTGAGGAAC CTGTTACCTCTCCAC ACATTGTGGGGAATA ACAACCTGAGGAACA TGTTACCTCTCCACT CATTGTGGGGAATAA CAACCTGAGGAACAT GTTACCTCTCCACTG ATTGTGGGGAATAAG AACCTGAGGAACATT TTACCTCTCCACTGT TTGTGGGGAATAAGC ACCTGAGGAACATTA TACCTCTCCACTGTG TGTGGGGAATAAGCC CCTGAGGAACATTAC ACCTCTCCACTGTGG GTGGGGAATAAGCCC CTGAGGAACATTACT CCTCTCCACTGTGGA TGGGGAATAAGCCCC TGAGGAACATTACTC CTCTCCACTGTGGAC GGGGAATAAGCCCCC GAGGAACATTACTCG TCTCCACTGTGGACT GGGAATAAGCCCCCA AGGAACATTACTCGG CTCCACTGTGGACTG GGAATAAGCCCCCAA GGAACATTACTCGGG TCCACTGTGGACTGG GAATAAGCCCCCAAA GAACATTACTCGGGG CCACTGTGGACTGGT AATAAGCCCCCAAAG AACATTACTCGGGGG CACTGTGGACTGGTC ATAAGCCCCCAAAGG ACATTACTCGGGGGG ACTGTGGACTGGTCC TAAGCCCCCAAAGGA CATTACTCGGGGGGC CTGTGGACTGGTCCC AAGCCCCCAAAGGAA ATTACTCGGGGGGCC TGTGGACTGGTCCCT AGCCCCCAAAGGAAT TTACTCGGGGGGCCA GTGGACTGGTCCCTG GCCCCCAAAGGAATG TACTCGGGGGGCCAT TGGACTGGTCCCTGA CCCCCAAAGGAATGT ACTCGGGGGGCCATC GGACTGGTCCCTGAT CCCCAAAGGAATGTG CTCGGGGGGCCATCA GACTGGTCCCTGATC CCCAAAGGAATGTGG TCGGGGGGCCATCAG ACTGGTCCCTGATCC CCAAAGGAATGTGGG CGGGCGGCCATCAGG CTGGTCCCTGATCCT CAAAGGAATGTGGGG GGGGGGCCATCAGGA TGGTCCCTGATCCTG AAAGGAATGTGGGGA GGGGGCCATCAGGAT GGTCCCTGATCCTGG AAGGAATGTGGGGAC GGGGCCATCAGGATT GTCCCTGATCCTGGA AGGAATGTGGGGACC GGGCCATCAGGATTG TCCCTGATCCTGGAT GGAATGTGGGGACCT GGCCATCAGGATTGA CCCTGATCCTGGATG GAATGTGGGGACCTG GCCATCAGGATTGAG CCTGATCCTGGATGC AATGTGGGGACCTGT CCATCAGGATTGAGA CTGATCCTGGATGCG ATGTGGGGACCTGTG CATCAGGATTGAGAA TGATCCTGGATGCGG TGTGGGGACCTGTGT ATCAGGATTGAGAAA GATCCTGGATGCGGT GTGGGGACCTGTGTC TCAGGATTGAGAAAA ATCCTGGATGCGGTG TGGGGACCTGTGTCC CAGGATTGAGAAAAA TCCTGGATGCGGTGT GGGGACCTGTGTCCA AGGATTGAGAAAAAT CCTGGATGCGGTGTC GGGACCTGTGTCCAG GGATTGAGAAAAATG CTGGATGCGGTGTCC GGACCTGTGTCCAGG GATTGAGAAAAATGC TGGATGCGGTGTCCA GACCTGTGTCCAGGG ATTGAGAAAAATGCT GGATGCGGTGTCCAA ACCTGTGTCCAGGGA TTGAGAAAAATGCTG GATGCGGTGTCCAAT CCTGTGTCCAGGGAC CTGTGTCCAGGGACC TGAGTACAACTACCG CGTGTGGGAAGCGGG TGTGTCCAGGGACCA GAGTACAACTACCGC GTGTGGGAAGCGGGC GTGTCCAGGGACCAT AGTACAACTACCGCT TGTGGGAAGCGGGCG TGTCCAGGGACCATG GTACAACTACCGCTG GTGGGAAGCGGGCGT GTCCAGGGACCATGG TACAACTACCGCTGC TGGGAAGCGGGCGTG TCCAGGGACCATGGA ACAACTACCGCTGCT GGGAAGCGGGCGTGC CCAGGGACCATGGAG CAACTACCGCTGCTG GGAAGCGGGCGTGCA CAGGGACCATGGAGG AACTACCGCTGCTGG GAAGCGGGCGTGCAC AGGGACCATGGAGGA ACTACCGCTGCTGGA AAGCGGGCGTGCACC GGGACCATGGAGGAG CTACCGCTGCTGGAC AGCGGGCGTGCACCG GGACCATGGAGGAGA TACCGCTGCTGGACC GCGGGCGTGCACCGA GACCATGGAGGAGAA ACCGCTGCTGGACCA CGGGCGTGCACCGAG ACCATGGAGGAGAAG CCGCTGCTGGACCAC GGGCGTGCACCGAGA CCATGGAGGAGAAGC CGCTGCTGGACCACA GGCGTGCACCGAGAA CATGGAGGAGAAGCC GCTGCTGGACCACAA GCGTGCACCGAGAAC ATGGAGGAGAAGCCG CTGCTGGACCACAAA CGTGCACCGAGAACA TGGAGGAGAAGCCGA TGCTGGACCACAAAC GTGCACCGAGAACAA GGAGGAGAAGCCGAT GCTGGACCACAAACC TGCACCGAGAACAAT GAGGAGAAGCCGATG CTGGACCACAAACCG GCACCGAGAACAATG AGGAGAAGCCGATGT TGGACCACAAACCGC CACCGAGAACAATGA GGAGAAGCCGATGTG GGACCACAAACCGCT ACCGAGAACAATGAG GAGAAGCCGATGTGT GACCACAAACCGCTG CCGAGAACAATGAGT AGAAGCCGATGTGTG ACCACAAACCGCTGC CGAGAACAATGAGTG GAAGCCGATGTGTGA CCACAAACCGCTGCC GAGAACAATGAGTGC AAGCCGATGTGTGAG CACAAACCGCTGCCA AGAACAATGAGTGCT AGCCGATGTGTGAGA ACAAACCGCTGCCAG GAACAATGAGTGCTG GCCGATGTGTGAGAA CAAACCGCTGCCAGA AACAATGAGTGCTGC CCGATGTGTGAGAAG AAACCGCTGCCAGAA ACAATGAGTGCTGCC CGATGTGTGAGAAGA AACCGCTGCCAGAAA CAATGAGTGCTGCCA GATGTGTGAGAAGAC ACCGCTGCCAGAAAA AATGAGTGCTGCCAC ATGTGTGAGAAGACC CCGCTGCCAGAAAAT ATGAGTGCTGCCACC TGTGTGAGAAGACCA CGCTGCCAGAAAATG TGAGTGCTGCCACCC GTGTGAGAAGACCAC GCTGCCAGAAAATGT GAGTGCTGCCACCCC TGTGAGAAGACCACC CTGCCAGAAAATGTG AGTGCTGCCACCCCG GTGAGAAGACCACCA TGCCAGAAAATGTGC GTGCTGCCACCCCGA TGAGAAGACCACCAT GCCAGAAAATGTGCC TGCTGCCACCCCGAG GAGAAGACCACCATC CCAGAAAATGTGCCC GCTGCCACCCCGAGT AGAAGACCACCATCA CAGAAAATGTGCCCA CTGCCACCCCGAGTG GAAGACCACCATCAA AGAAAATGTGCCCAA TGCCACCCCGAGTGC AAGACCACCATCAAC GAAAATGTGCCCAAG GCCACCCCGAGTGCC AGACCACCATCAACA AAAATGTGCCCAAGC CCACCCCGAGTGCCT GACCACCATCAACAA AAATGTGCCCAAGCA CACCCCGAGTGCCTG ACCACCATCAACAAT AATGTGCCCAAGCAC ACCCCGAGTGCCTGG CCACCATCAACAATG ATGTGCCCAAGCACG CCCCGAGTGCCTGGG CACCATCAACAATGA TGTGCCCAAGCACGT CCCGAGTGCCTGGGC ACCATCAACAATGAG GTGCCCAAGCACGTG CCGAGTGCCTGGGCA CCATCAACAATGAGT TGCCCAAGCACGTGT CGAGTGCCTGGGCAG CATCAACAATGAGTA GCCCAAGCACGTGTG GAGTGCCTGGGCAGC ATCAACAATGAGTAC CCCAAGCACGTGTGG AGTGCCTGGGCAGCT TCAACAATGAGTACA CCAAGCACGTGTGGG GTGCCTGGGCAGCTG CAACAATGAGTACAA CAAGCACGTGTGGGA TGCCTGGGCAGCTGC AACAATGAGTACAAC AAGCACGTGTGGGAA GCCTGGGCAGCTGCA ACAATGAGTACAACT AGCACGTGTGGGAAG CCTGGGCAGCTGCAG CAATGAGTACAACTA GCACGTGTGGGAAGC CTGGGCAGCTGCAGC AATGAGTACAACTAC CACGTGTGGGAAGCG TGGGCAGCTGCAGCG ATGAGTACAACTACC ACGTGTGGGAAGCGG GGGCAGCTGCAGCGC GGCAGCTGCAGCGCG CTATGCCGGTGTCTG GGCGCTGTGTGGACC GCAGCTGCAGCGCGC TATGCCGGTGTCTGT GCGCTGTGTGGACCG CAGCTGCAGCGCGCC ATGCCGGTGTCTGTG CGCTGTGTGGACCGT AGCTGCAGCGCGCCT TGCCGGTGTCTGTGT GCTGTGTGGACCGTG GCTGCAGCGCGCCTG GCCGGTGTCTGTGTG CTGTGTGGACCGTGA CTGCAGCGCGCCTGA CCGGTGTCTGTGTGC TGTGTGGACCGTGAC TGCAGCGCGCCTGAC CGGTGTCTGTGTGCC GTGTGGACCGTGACT GCAGCGCGCCTGACA GGTGTCTGTGTGCCT TGTGGACCGTGACTT CAGCGCGCCTGACAA GTGTCTGTGTGCCTG GTGGACCGTGACTTC AGCGCGCCTGACAAC TGTCTGTGTGCCTGC TGGACCGTGACTTCT GCGCGCCTGACAACG GTCTGTGTGCCTGCC GGACCGTGACTTCTG CGCGCCTGACAACGA TCTGTGTGCCTGCCT GACCGTGACTTCTGC GCGCCTGACAACGAC CTGTGTGCCTGCCTG ACCGTGACTTCTGCG CGCCTGACAACGACA TGTGTGCCTGCCTGC CCGTGACTTCTGCGC GCCTGACAACGACAC GTGTGCCTGCCTGCC CGTGACTTCTGCGCC CCTGACAACGACACG TGTGCCTGCCTGCCC GTGACTTCTGCGCCA CTGACAACGACACGG GTGCCTGCCTGCCCG TGACTTCTGCGCCAA TGACAACGACACGGC TGCCTGCCTGCCCGC GACTTCTGCGCCAAC GACAACGACACGGCC GCCTGCCTGCCCGCC ACTTCTGCGCCAACA ACAACGACACGGCCT CCTGCCTGCCCGCCC CTTCTGCGCCAACAT CAACGACACGGCCTG CTGCCTGCCCGCCCA TTCTGCGCCAACATC AACGACACGGCCTGT TGCCTGCCCGCCCAA TCTGCGCCAACATCC ACGACACGGCCTGTG GCCTGCCCGCCCAAC CTGCGCCAACATCCT CGACACGGCCTGTGT CCTGCCCGCCCAACA TGCGCCAACATCCTC GACACGGCCTGTGTA CTGCCCGCCCAACAC GCGCCAACATCCTCA ACACGGCCTGTGTAG TGCCCGCCCAACACC CGCCAACATCCTCAG CACGGCCTGTGTAGC GCCCGCCCAACACCT GCCAACATCCTCAGC ACGGCCTGTGTAGCT CCCGCCCAACACCTA CCAACATCCTCAGCG CGGCCTGTGTAGCTT CCGCCCAACACCTAC CAACATCCTCAGCGC GGCCTGTGTAGCTTG CGCCCAACACCTACA AACATCCTCAGCGCC GCCTGTGTAGCTTGC GCCCAACACCTACAG ACATCCTCAGCGCCG CCTGTGTAGCTTGCC CCCAACACCTACAGG CATCCTCAGCGCCGA CTGTGTAGCTTGCCG CCAACACCTACAGGT ATCCTCAGCGCCGAG TGTGTAGCTTGCCGC CAACACCTACAGGTT TCCTCAGCGCCGAGA GTGTAGCTTGCCGCC AACACCTACAGGTTT CCTCAGCGCCGAGAG TGTAGCTTGCCGCCA ACACCTACAGGTTTG CTCAGCGCCGAGAGC GTAGCTTGCCGCCAC CACCTACAGGTTTGA TCAGCGCCGAGAGCA TAGCTTGCCGCCACT ACCTACAGGTTTGAG CAGCGCCGAGAGCAG AGCTTGCCGCCACTA CCTACAGGTTTGAGG AGCGCCGAGAGCAGC GCTTGCCGCCACTAC CTACAGGTTTGAGGG GCGCCGAGAGCAGCG CTTGCCGCCACTACT TACAGGTTTGAGGGC CGCCGAGAGCAGCGA TTGCCGCCACTACTA ACAGGTTTGAGGGCT GCCGAGAGCAGCGAC TGCCGCCACTACTAC CAGGTTTGAGGGCTG CCGAGAGCAGCGACT GCCGCCACTACTACT AGGTTTGAGGGCTGG CGAGAGCAGCGACTC CCGCCACTACTACTA GGTTTGAGGGCTGGC GAGAGCAGCGACTCC CGCCACTACTACTAT GTTTGAGGGCTGGCG AGAGCAGCGACTCCG GCCACTACTACTATG TTTGAGGGCTGGCGC GAGCAGCGACTCCGA CCACTACTACTATGC TTGAGGGCTGGCGCT AGCAGCGACTCCGAG CACTACTACTATGCC TGAGGGCTGGCGCTG GCAGCGACTCCGAGG ACTACTACTATGCCG GAGGGCTGGCGCTGT CAGCGACTCCGAGGG CTACTACTATGCCGG AGGGCTGGCGCTGTG AGCGACTCCGAGGGG TACTACTATGCCGGT GGGCTGGCGCTGTGT GCGACTCCGAGGGGT ACTACTATGCCGGTG GGCTGGCGCTGTGTG CGACTCCGAGGGGTT CTACTATGCCGGTGT GCTGGCGCTGTGTGG GACTCCGAGGGGTTT TACTATGCCGGTGTC CTGGCGCTGTGTGGA ACTCCGAGGGGTTTG ACTATGCCGGTGTCT TGGCGCTGTGTGGAC CTCCGAGGGGTTTGT TCCGAGGGGTTTGTG CATCCGCAACGGCAG AGGTCTGTGAGGAAG CCGAGGGGTTTGTGA ATCCGCAACGGCAGC GGTCTGTGAGGAAGA CGAGGGGTTTGTGAT TCCGCAACGGCAGCC GTCTGTGAGGAAGAA GAGGGGTTTGTGATC CCGCAACGGCAGCCA TCTGTGAGGAAGAAA AGGGGTTTGTGATCC CGCAACGGCAGCCAG CTGTGAGGAAGAAAA GGGGTTTGTGATCCA GCAACGGCAGCCAGA TGTGAGGAAGAAAAG GGGTTTGTGATCCAC CAACGGCAGCCAGAG GTGAGGAAGAAAAGA GGTTTGTGATCCACG AACGGCAGCCAGAGC TGAGGAAGAAAAGAA GTTTGTGATCCACGA ACGGCAGCCAGAGCA GAGGAAGAAAAGAAA TTTGTGATCCACGAC CGGCAGCCAGAGCAT AGGAAGAAAAGAAAA TTGTGATCCACGACG GGCAGCCAGAGCATG GGAAGAAAAGAAAAC TGTGATCCACGACGG GCAGCCAGAGCATGT GAAGAAAAGAAAACA GTGATCCACGACGGC CAGCCAGAGCATGTA AAGAAAAGAAAACAA TGATCCACGACGGCG AGCCAGAGCATGTAC AGAAAAGAAAACAAA GATCCACGACGGCGA GCCAGAGCATGTACT GAAAAGAAAACAAAG ATCCACGACGGCGAG CCAGAGCATGTACTG AAAAGAAAACAAAGA TCCACGACGGCGAGT CAGAGCATGTACTGC AAAGAAAACAAAGAC CCACGACGGCGAGTG AGAGCATGTACTGCA AAGAAAACAAAGACC CACGACGGCGAGTGC GAGCATGTACTGCAT AGAAAACAAAGACCA ACGACGGCGAGTGCA AGCATGTACTGCATC GAAAACAAAGACCAT CGACGGCGAGTGCAT GCATGTACTGCATCC AAAACAAAGACCATT GACGGCGAGTGCATG CATGTACTGCATCCC AAACAAAGACCATTG ACGGCGAGTGCATGC ATGTACTGCATCCCT AACAAAGACCATTGA CGGCGAGTGCATGCA TGTACTGCATCCCTT ACAAAGACCATTGAT GGCGAGTGCATGCAG GTACTGCATCCCTTG CAAAGACCATTGATT GCGAGTGCATGCAGG TACTGCATCCCTTGT AAAGACCATTGATTC CGAGTGCATGCAGGA ACTGCATCCCTTGTG AAGACCATTGATTCT GAGTGCATGCAGGAG CTGCATCCCTTGTGA AGACCATTGATTCTG AGTGCATGCAGGAGT TGCATCCCTTGTGAA GACCATTGATTCTGT GTGCATGCAGGAGTG GCATCCCTTGTGAAG ACCATTGATTCTGTT TGCATGCAGGAGTGC CATCCCTTGTGAAGG CCATTGATTCTGTTA GCATGCAGGAGTGCC ATCCCTTGTGAAGGT CATTGATTCTGTTAC CATGCAGGAGTGCCC TCCCTTGTGAAGGTC ATTGATTCTGTTACT ATGCAGGAGTGCCCC CCCTTGTGAAGGTCC TTGATTCTGTTACTT TGCAGGAGTGCCCCT CCTTGTGAAGGTCCT TGATTCTGTTACTTC GCAGGAGTGCCCCTC CTTGTGAAGGTCCTT GATTCTGTTACTTCT CAGGAGTGCCCCTCG TTGTGAAGGTCCTTG ATTCTGTTACTTCTG AGGAGTGCCCCTCGG TGTGAAGGTCCTTGC TTCTGTTACTTCTGC GGAGTGCCCCTCGGG GTGAAGGTCCTTGCC TCTGTTACTTCTGCT GAGTGCCCCTCGGGC TGAAGGTCCTTGCCC CTGTTACTTCTGCTC AGTGCCCCTCGGGCT GAAGGTCCTTGCCCG TGTTACTTCTGCTCA GTGCCCCTCGGGCTT AAGGTCCTTGCCCGA GTTACTTCTGCTCAG TGCCCCTCGGGCTTC AGGTCCTTGCCCGAA TTACTTCTGCTCAGA GCCCCTCGGGCTTCA GGTCCTTGCCCGAAG TACTTCTGCTCAGAT CCCCTCGGGCTTCAT GTCCTTGCCCGAAGG ACTTCTGCTCAGATG CCCTCGGGCTTCATC TCCTTGCCCGAAGGT CTTCTGCTCAGATGC CCTCGGGCTTCATCC CCTTGCCCGAAGGTC TTCTGCTCAGATGCT CTCGGGCTTCATCCG CTTGCCCGAAGGTCT TCTGCTCAGATGCTC TCGGGCTTCATCCGC TTGCCCGAAGGTCTG CTGCTCAGATGCTCC CGGGCTTCATCCGCA TGCCCGAAGGTCTGT TGCTCAGATGCTCCA GGGCTTCATCCGCAA GCCCGAAGGTCTGTG GCTCAGATGCTCCAA GGCTTCATCCGCAAC CCCGAAGGTCTGTGA CTCAGATGCTCCAAG GCTTCATCCGCAACG CCGAAGGTCTGTGAG TCAGATGCTCCAAGG CTTCATCCGCAACGG CGAAGGTCTGTGAGG CAGATGCTCCAAGGA TTCATCCGCAACGGC GAAGGTCTGTGAGGA AGATGCTCCAAGGAT TCATCCGCAACGGCA AAGGTCTGTGAGGAA GATGCTCCAAGGATG ATGCTCCAAGGATGC GAATAACATTGCTTC CCTACGTGAAGATCC TGCTCCAAGGATGCA AATAACATTGCTTCA CTACGTGAAGATCCG GCTCCAAGGATGCAC ATAACATTGCTTCAG TACGTGAAGATCCGC CTCCAAGGATGCACC TAACATTGCTTCAGA ACGTGAAGATCCGCC TCCAAGGATGCACCA AACATTGCTTCAGAG CGTGAAGATCCGCCA CCAAGGATGCACCAT ACATTGCTTCAGAGC GTGAAGATCCGCCAT CAAGGATGCACCATC CATTGCTTCAGAGCT TGAAGATCCGCCATT AAGGATGCACCATCT ATTGCTTCAGAGCTG GAAGATCCGCCATTC AGGATGCACCATCTT TTGCTTCAGAGCTGG AAGATCCGCCATTCT GGATGCACCATCTTC TGCTTCAGAGCTGGA AGATCCGCCATTCTC GATGCACCATCTTCA GCTTCAGAGCTGGAG GATCCGCCATTCTCA ATGCACCATCTTCAA CTTCAGAGCTGGAGA ATCCGCCATTCTCAT TGCACCATCTTCAAG TTCAGAGCTGGAGAA TCCGCCATTCTCATG GCACCATCTTCAAGG TCAGAGCTGGAGAAC CCGCCATTCTCATGC CACCATCTTCAAGGG CAGAGCTGGAGAACT CGCCATTCTCATGCC ACCATCTTCAAGGGC AGAGCTGGAGAACTT GCCATTCTCATGCCT CCATCTTCAAGGGCA GAGCTGGAGAACTTC CCATTCTCATGCCTT CATCTTCAAGGGCAA AGCTGGAGAACTTCA CATTCTCATGCCTTG ATCTTCAAGGGCAAT GCTGGAGAACTTCAT ATTCTCATGCCTTGG TCTTCAAGGGCAATT CTGGAGAACTTCATG TTCTCATGCCTTGGT CTTCAAGGGCAATTT TGGAGAACTTCATGG TCTCATGCCTTGGTC TTCAAGGGCAATTTG GGAGAACTTCATGGG CTCATGCCTTGGTCT TCAAGGGCAATTTGC GAGAACTTCATGGGG TCATGCCTTGGTCTC CAAGGGCAATTTGCT AGAACTTCATGGGGC CATGCCTTGGTCTCC AAGGGCAATTTGCTC GAACTTCATGGGGCT ATGCCTTGGTCTCCT AGGGCAATTTGCTCA AACTTCATGGGGCTC TGCCTTGGTCTCCTT GGGCAATTTGCTCAT ACTTCATGGGGCTCA GCCTTGGTCTCCTTG GGCAATTTGCTCATT CTTCATGGGGCTCAT CCTTGGTCTCCTTGT GCAATTTGCTCATTA TTCATGGGGCTCATC CTTGGTCTCCTTGTC CAATTTGCTCATTAA TCATGGGGCTCATCG TTGGTCTCCTTGTCC AATTTGCTCATTAAC CATGGGGCTCATCGA TGGTCTCCTTGTCCT ATTTGCTCATTAACA ATGGGGCTCATCGAG GGTCTCCTTGTCCTT TTTGCTCATTAACAT TGGGGCTCATCGAGG GTCTCCTTGTCCTTC TTGCTCATTAACATC GGGGCTCATCGAGGT TCTCCTTGTCCTTCC TGCTCATTAACATCC GGGCTCATCGAGGTG CTCCTTGTCCTTCCT GCTCATTAACATCCG GGCTCATCGAGGTGG TCCTTGTCCTTCCTA CTCATTAACATCCGA GCTCATCGAGGTGGT CCTTGTCCTTCCTAA TCATTAACATCCGAC CTCATCGAGGTGGTG CTTGTCCTTCCTAAA CATTAACATCCGACG TCATCGAGGTGGTGA TTGTCCTTCCTAAAA ATTAACATCCGACGG CATCGAGGTGGTGAC TGTCCTTCCTAAAAA TTAACATCCGACGGG ATCGAGGTGGTGACG GTCCTTCCTAAAAAA TAACATCCGACGGGG TCGAGGTGGTGACGG TCCTTCCTAAAAAAC AACATCCGACGGGGG CGAGGTGGTGACGGG CCTTCCTAAAAAACC ACATCCGACGGGGGA GAGGTGGTGACGGGC CTTCCTAAAAAACCT CATCCGACGGGGGAA AGGTGGTGACGGGCT TTCCTAAAAAACCTT ATCCGACGGGGGAAT GGTGGTGACGGGCTA TCCTAAAAAACCTTC TCCGACGGGGGAATA GTGGTGACGGGCTAC CCTAAAAAACCTTCG CCGACGGGGGAATAA TGGTGACGGGCTACG CTAAAAAACCTTCGC CGACGGGGGAATAAC GGTGACGGGCTACGT TAAAAAACCTTCGCC GACGGGGGAATAACA GTGACGGGCTACGTG AAAAAACCTTCGCCT ACGGGGGAATAACAT TGACGGGCTACGTGA AAAAACCTTCGCCTC CGGGGGAATAACATT GACGGGCTACGTGAA AAAACCTTCGCCTCA GGGGGAATAACATTG ACGGGCTACGTGAAG AAACCTTCGCCTCAT GGGGAATAACATTGC CGGGCTACGTGAAGA AACCTTCGCCTCATC GGGAATAACATTGCT GGGCTACGTGAAGAT ACCTTCGCCTCATCC GGAATAACATTGCTT GGCTACGTGAAGATC CCTTCGCCTCATCCT CTTCGCCTCATCCTA CGACAACCAGAACTT AAGCAGGGAAAATGT TTCGCCTCATCCTAG GACAACCAGAACTTG AGCAGGGAAAATGTA TCGCCTCATCCTAGG ACAACCAGAACTTGC GCAGGGAAAATGTAC CGCCTCATCCTAGGA CAACCAGAACTTGCA CAGGGAAAATGTACT GCCTCATCCTAGGAG AACCAGAACTTGCAG AGGGAAAATGTACTT CCTCATCCTAGGAGA ACCAGAACTTGCAGC GGGAAAATGTACTTT CTCATCCTAGGAGAG CCAGAACTTGCAGCA GGAAAATGTACTTTG TCATCCTAGGAGAGG CAGAACTTGCAGCAA GAAAATGTACTTTGC CATCCTAGGAGAGGA AGAACTTGCAGCAAC AAAATGTACTTTGCT ATCCTAGGAGAGGAG GAACTTGCAGCAACT AAATGTACTTTGCTT TCCTAGGAGAGGAGC AACTTGCAGCAACTG AATGTACTTTGCTTT CCTAGGAGAGGAGCA ACTTGCAGCAACTGT ATGTACTTTGCTTTC CTAGGAGAGGAGCAG CTTGCAGCAACTGTG TGTACTTTGCTTTCA TAGGAGAGGAGCAGC TTGCAGCAACTGTGG GTACTTTGCTTTCAA AGGAGAGGAGCAGCT TGCAGCAACTGTGGG TACTTTGCTTTCAAT GGAGAGGAGCAGCTA GCAGCAACTGTGGGA ACTTTGCTTTCAATC GAGAGGAGCAGCTAG CAGCAACTGTGGGAC CTTTGCTTTCAATCC AGAGGAGCAGCTAGA AGCAACTGTGGGACT TTTGCTTTCAATCCC GAGGAGCAGCTAGAA GCAACTGTGGGACTG TTGCTTTCAATCCCA AGGAGCAGCTAGAAG CAACTGTGGGACTGG TGCTTTCAATCCCAA GGAGCAGCTAGAAGG AACTGTGGGACTGGG GCTTTCAATCCCAAA GAGCAGCTAGAAGGG ACTGTGGGACTGGGA CTTTCAATCCCAAAT AGCAGCTAGAAGGGA CTGTGGGACTGGGAC TTTCAATCCCAAATT GCAGCTAGAAGGGAA TGTGGGACTGGGACC TTCAATCCCAAATTA CAGCTAGAAGGGAAT GTGGGACTGGGACCA TCAATCCCAAATTAT AGCTAGAAGGGAATT TGGGACTGGGACCAC CAATCCCAAATTATG GCTAGAAGGGAATTA GGGACTGGGACCACC AATCCCAAATTATGT CTAGAAGGGAATTAC GGACTGGGACCACCG ATCCCAAATTATGTG TAGAAGGGAATTACT GACTGGGACCACCGC TCCCAAATTATGTGT AGAAGGGAATTACTC ACTGGGACCACCGCA CCCAAATTATGTGTT GAAGGGAATTACTCC CTGGGACCACCGCAA CCAAATTATGTGTTT AAGGGAATTACTCCT TGGGACCACCGCAAC CAAATTATGTGTTTC AGGGAATTACTCCTT GGGACCACCGCAACC AAATTATGTGTTTCC GGGAATTACTCCTTC GGACCACCGCAACCT AATTATGTGTTTCCG GGAATTACTCCTTCT GACCACCGCAACCTG ATTATGTGTTTCCGA GAATTACTCCTTCTA ACCACCGCAACCTGA TTATGTGTTTCCGAA AATTACTCCTTCTAC CCACCGCAACCTGAC TATGTGTTTCCGAAA ATTACTCCTTCTACG CACCGCAACCTGACC ATGTGTTTCCGAAAT TTACTCCTTCTACGT ACCGCAACCTGACCA TGTGTTTCCGAAATT TACTCCTTCTACGTC CCGCAACCTGACCAT GTGTTTCCGAAATTT ACTCCTTCTACGTCC CGCAACCTGACCATC TGTTTCCGAAATTTA CTCCTTCTACGTCCT GCAACCTGACCATCA GTTTCCGAAATTTAC TCCTTCTACGTCCTC CAACCTGACCATCAA TTTCCGAAATTTACC CCTTCTACGTCCTCG AACCTGACCATCAAA TTCCGAAATTTACCG CTTCTACGTCCTCGA ACCTGACCATCAAAG TCCGAAATTTACCGC TTCTACGTCCTCGAC CCTGACCATCAAAGC CCGAAATTTACCGCA TCTACGTCCTCGACA CTGACCATCAAAGCA CGAAATTTACCGCAT CTACGTCCTCGACAA TGACCATCAAAGCAG GAAATTTACCGCATG TACGTCCTCGACAAC GACCATCAAAGCAGG AAATTTACCGCATGG ACGTCCTCGACAACC ACCATCAAAGCAGGG AATTTACCGCATGGA CGTCCTCGACAACCA CCATCAAAGCAGGGA ATTTACCGCATGGAG GTCCTCGACAACCAG CATCAAAGCAGGGAA TTTACCGCATGGAGG TCCTCGACAACCAGA ATCAAAGCAGGGAAA TTACCGCATGGAGGA CCTCGACAACCAGAA TCAAAGCAGGGAAAA TACCGCATGGAGGAA CTCGACAACCAGAAC CAAAGCAGGGAAAAT ACCGCATGGAGGAAG TCGACAACCAGAACT AAAGCAGGGAAAATG CCGCATGGAGGAAGT CGCATGGAGGAAGTG CAGGAACAACGGGGA CCACCACGTCGAAGA GCATGGAGGAAGTGA AGGAACAACGGGGAG CACCACGTCGAAGAA CATGGAGGAAGTGAC GGAACAACGGGGAGA ACCACGTCGAAGAAT ATGGAGGAAGTGACG GAACAACGGGGAGAG CCACGTCGAAGAATC TGGAGGAAGTGACGG AACAACGGGGAGAGA CACGTCGAAGAATCG GGAGGAAGTGACGGG ACAACGGGGAGAGAG ACGTCGAAGAATCGC GAGGAAGTGACGGGG CAACGGGGAGAGAGC CGTCGAAGAATCGCA AGGAAGTGACGGGGA AACGGGGAGAGAGCC GTCGAAGAATCGCAT GGAAGTGACGGGGAC ACGGGGAGAGAGCCT TCGAAGAATCGCATC GAAGTGACGGGGACT CGGGGAGAGAGCCTC CGAAGAATCGCATCA AAGTGACGGGGACTA GGGGAGAGAGCCTCC GAAGAATCGCATCAT AGTGACGGGGACTAA GGGAGAGAGCCTCCT AAGAATCGCATCATC GTGACGGGGACTAAA GGAGAGAGCCTCCTG AGAATCGCATCATCA TGACGGGGACTAAAG GAGAGAGCCTCCTGT GAATCGCATCATCAT GACGGGGACTAAAGG AGAGAGCCTCCTGTG AATCGCATCATCATA ACGGGGACTAAAGGG GAGAGCCTCCTGTGA ATCGCATCATCATAA CGGGGACTAAAGGGC AGAGCCTCCTGTGAA TCGCATCATCATAAC GGGGACTAAAGGGCG GAGCCTCCTGTGAAA CGCATCATCATAACC GGGACTAAAGGGCGC AGCCTCCTGTGAAAG GCATCATCATAACCT GGACTAAAGGGCGCC GCCTCCTGTGAAAGT CATCATCATAACCTG GACTAAAGGGCGCCA CCTCCTGTGAAAGTG ATCATCATAACCTGG ACTAAAGGGCGCCAA CTCCTGTGAAAGTGA TCATCATAACCTGGC CTAAAGGGCGCCAAA TCCTGTGAAAGTGAC CATCATAACCTGGCA TAAAGGGCGCCAAAG CCTGTGAAAGTGACG ATCATAACCTGGCAC AAAGGGCGCCAAAGC CTGTGAAAGTGACGT TCATAACCTGGCACC AAGGGCGCCAAAGCA TGTGAAAGTGACGTC CATAACCTGGCACCG AGGGCGCCAAAGCAA GTGAAAGTGACGTCC ATAACCTGGCACCGG GGGCGCCAAAGCAAA TGAAAGTGACGTCCT TAACCTGGCACCGGT GGCGCCAAAGCAAAG GAAAGTGACGTCCTG AACCTGGCACCGGTA GCGCCAAAGCAAAGG AAAGTGACGTCCTGC ACCTGGCACCGGTAC CGCCAAAGCAAAGGG AAGTGACGTCCTGCA CCTGGCACCGGTACC GCCAAAGCAAAGGGG AGTGACGTCCTGCAT CTGGCACCGGTACCG CCAAAGCAAAGGGGA GTGACGTCCTGCATT TGGCACCGGTACCGG CAAAGCAAAGGGGAC TGACGTCCTGCATTT GGCACCGGTACCGGC AAAGCAAAGGGGACA GACGTCCTGCATTTC GCACCGGTACCGGCC AAGCAAAGGGGACAT ACGTCCTGCATTTCA CACCGGTACCGGCCC AGCAAAGGGGACATA CGTCCTGCATTTCAC ACCGGTACCGGCCCC GCAAAGGGGACATAA GTCCTGCATTTCACC CCGGTACCGGCCCCC CAAAGGGGACATAAA TCCTGCATTTCACCT CGGTACCGGCCCCCT AAAGGGGACATAAAC CCTGCATTTCACCTC GGTACCGGCCCCCTG AAGGGGACATAAACA CTGCATTTCACCTCC GTACCGGCCCCCTGA AGGGGACATAAACAC TGCATTTCACCTCCA TACCGGCCCCCTGAC GGGGACATAAACACC GCATTTCACCTCCAC ACCGGCCCCCTGACT GGGACATAAACACCA CATTTCACCTCCACC CCGGCCCCCTGACTA GGACATAAACACCAG ATTTCACCTCCACCA CGGCCCCCTGACTAC GACATAAACACCAGG TTTCACCTCCACCAC GGCCCCCTGACTACA ACATAAACACCAGGA TTCACCTCCACCACC GCCCCCTGACTACAG CATAAACACCAGGAA TCACCTCCACCACCA CCCCCTGACTACAGG ATAAACACCAGGAAC CACCTCCACCACCAC CCCCTGACTACAGGG TAAACACCAGGAACA ACCTCCACCACCACG CCCTGACTACAGGGA AAACACCAGGAACAA CCTCCACCACCACGT CCTGACTACAGGGAT AACACCAGGAACAAC CTCCACCACCACGTC CTGACTACAGGGATC ACACCAGGAACAACG TCCACCACCACGTCG TGACTACAGGGATCT CACCAGGAACAACGG CCACCACCACGTCGA GACTACAGGGATCTC ACCAGGAACAACGGG CACCACCACGTCGAA ACTACAGGGATCTCA CCAGGAACAACGGGG ACCACCACGTCGAAG CTACAGGGATCTCAT TACAGGGATCTCATC CACAGAGTATGATGG TGGACCTCCCGCCCA ACAGGGATCTCATCA ACAGAGTATGATGGG GGACCTCCCGCCCAA CAGGGATCTCATCAG CAGAGTATGATGGGC GACCTCCCGCCCAAC AGGGATCTCATCAGC AGAGTATGATGGGCA ACCTCCCGCCCAACA GGGATCTCATCAGCT GAGTATGATGGGCAG CCTCCCGCCCAACAA GGATCTCATCAGCTT AGTATGATGGGCAGG CTCCCGCCCAACAAG GATCTCATCAGCTTC GTATGATGGGCAGGA TCCCGCCCAACAAGG ATCTCATCAGCTTCA TATGATGGGCAGGAT CCCGCCCAACAAGGA TCTCATCAGCTTCAC ATGATGGGCAGGATG CCGCCCAACAAGGAC CTCATCAGCTTCACC TGATGGGCAGGATGC CGCCCAACAAGGACG TCATCAGCTTCACCG GATGGGCAGGATGCC GCCCAACAAGGACGT CATCAGCTTCACCGT ATGGGCAGGATGCCT CCCAACAAGGACGTG ATCAGCTTCACCGTT TGGGCAGGATGCCTG CCAACAAGGACGTGG TCAGCTTCACCGTTT GGGCAGGATGCCTGC CAACAAGGACGTGGA CAGCTTCACCGTTTA GGCAGGATGCCTGCG AACAAGGACGTGGAG AGCTTCACCGTTTAC GCAGGATGCCTGCGG ACAAGGACGTGGAGC GCTTCACCGTTTACT CAGGATGCCTGCGGC CAAGGACGTGGAGCC CTTCACCGTTTACTA AGGATGCCTGCGGCT AAGGACGTGGAGCCC TTCACCGTTTACTAC GGATGCCTGCGGCTC AGGACGTGGAGCCCG TCACCGTTTACTACA GATGCCTGCGGCTCC GGACGTGGAGCCCGG CACCGTTTACTACAA ATGCCTGCGGCTCCA GACGTGGAGCCCGGC ACCGTTTACTACAAG TGCCTGCGGCTCCAA ACGTGGAGCCCGGCA CCGTTTACTACAAGG GCCTGCGGCTCCAAC CGTGGAGCCCGGCAT CGTTTACTACAAGGA CCTGCGGCTCCAACA GTGGAGCCCGGCATC GTTTACTACAAGGAA CTGCGGCTCCAACAG TGGAGCCCGGCATCT TTTACTACAAGGAAG TGCGGCTCCAACAGC GGAGCCCGGCATCTT TTACTACAAGGAAGC GCGGCTCCAACAGCT GAGCCCGGCATCTTA TACTACAAGGAAGCA CGGCTCCAACAGCTG AGCCCGGCATCTTAC ACTACAAGGAAGCAC GGCTCCAACAGCTGG GCCCGGCATCTTACT CTACAAGGAAGCACC GCTCCAACAGCTGGA CCCGGCATCTTACTA TACAAGGAAGCACCC CTCCAACAGCTGGAA CCGGCATCTTACTAC ACTAGGAAGCACCCT TCCAACAGCTGGAAC CGGCATCTTACTACA CAAGGAAGCACCCTT CCAACAGCTGGAACA GGCATCTTACTACAT AAGGAAGCACCCTTT CAACAGCTGGAACAT GCATCTTACTACATG AGGAAGCACCCTTTA AACAGCTGGAACATG CATCTTACTACATGG GGAAGCACCCTTTAA ACAGCTGGAACATGG ATCTTACTACATGGG GAAGCACCCTTTAAG CAGCTGGAACATGGT TCTTACTACATGGGC AAGCACCCTTTAAGA AGCTGGAACATGGTG CTTACTACATGGGCT AGCACCCTTTAAGAA GCTGGAACATGGTGG TTACTACATGGGCTG GCACCCTTTAAGAAT CTGGAACATGGTGGA TACTACATGGGCTGA CACCCTTTAAGAATG TGGAACATGGTGGAC ACTACATGGGCTGAA ACCCTTTAAGAATGT GGAACATGGTGGACG CTACATGGGCTGAAG CCCTTTAAGAATGTC GAACATGGTGGACGT TACATGGGCTGAAGC CCTTTAAGAATGTCA AACATGGTGGACGTG ACATGGGCTGAAGCC CTTTAAGAATGTCAC ACATGGTGGACGTGG CATGGGCTGAAGCCC TTTAAGAATGTCACA CATGGTGGACGTGGA ATGGGCTGAAGCCCT TTAAGAATGTCACAG ATGGTGGACGTGGAC TGGGCTGAAGCCCTG TAAGAATGTCACAGA TGGTGGACGTGGACC GGGCTGAAGCCCTGG AAGAATGTCACAGAG GGTGGACGTGGACCT GGCTGAAGCCCTGGA AGAATGTCACAGAGT GTGGACGTGGACCTC GCTGAAGCCCTGGAC GAATGTCACAGAGTA TGGACGTGGACCTCC CTGAAGCCCTGGACT AATGTCACAGAGTAT GGACGTGGACCTCCC TGAAGCCCTGGACTC ATGTCACAGAGTATG GACGTGGACCTCCCG GAAGCCCTGGACTCA TGTCACAGAGTATGA ACGTGGACCTCCCGC AAGCCCTGGACTCAG GTCACAGAGTATGAT CGTGGACCTCCCGCC AGCCCTGGACTCAGT TCACAGAGTATGATG GTGGACCTCCCGCCC GCCCTGGACTCAGTA CCCTGGACTCAGTAC CGACCATATCCGTGG TTCCTTCCATTCCCT CCTGGACTCAGTACG GACCATATCCGTGGG TCCTTCCATTCCCTT CTGGACTCAGTACGC ACCATATCCGTGGGG CCTTCCATTCCCTTG TGGACTCAGTACGCC CCATATCCGTGGGGC CTTCCATTCCCTTGG GGACTCAGTACGCCG CATATCCGTGGGGCC TTCCATTCCCTTGGA GACTCAGTACGCCGT ATATCCGTGGGGCCA TCCATTCCCTTGGAC ACTCAGTACGCCGTT TATCCGTGGGGCCAA CCATTCCCTTGGACG CTCAGTACGCCGTTT ATCCGTGGGGCCAAG CATTCCCTTGGACGT TCAGTACGCCGTTTA TCCGTGGGGCCAAGA ATTCCCTTGGACGTT CAGTACGCCGTTTAC CCGTGGGGCCAAGAG TTCCCTTGGACGTTC AGTACGCCGTTTACG CGTGGGGCCAAGAGT TCCCTTGGACGTTCT GTACGCCGTTTACGT GTGGGGCCAAGAGTG CCCTTGGACGTTCTT TACGCCGTTTACGTC TGGGGCCAAGAGTGA CCTTGGACGTTCTTT ACGCCGTTTACGTCA GGGGCCAAGAGTGAG CTTGGACGTTCTTTC CGCCGTTTACGTCAA GGGCCAAGAGTGAGA TTGGACGTTCTTTCA GCCGTTTACGTCAAG GGCCAAGAGTGAGAT TGGACGTTCTTTCAG CCGTTTACGTCAAGG GCCAAGAGTGAGATC GGACGTTCTTTCAGC CGTTTACGTCAAGGC CCAAGAGTGAGATCT GACGTTCTTTCAGCA GTTTACGTCAAGGCT CAAGAGTGAGATCTT ACGTTCTTTCAGCAT TTTACGTCAAGGCTG AAGAGTGAGATCTTG CGTTCTTTCAGCATC TTACGTCAAGGCTGT AGAGTGAGATCTTGT GTTCTTTCAGCATCG TACGTCAAGGCTGTG GAGTGAGATCTTGTA TTCTTTCAGCATCGA ACGTCAAGGCTGTGA AGTGAGATCTTGTAC TCTTTCAGCATCGAA CGTCAAGGCTGTGAC GTGAGATCTTGTACA CTTTCAGCATCGAAC GTCAAGGCTGTGACC TGAGATCTTGTACAT TTTCAGCATCGAACT TCAAGGCTGTGACCC GAGATCTTGTACATT TTCAGCATCGAACTC CAAGGCTGTGACCCT AGATCTTGTACATTC TCAGCATCGAACTCC AAGGCTGTGACCCTC GATCTTGTACATTCG CAGCATCGAACTCCT AGGCTGTGACCCTCA ATCTTGTACATTCGC AGCATCGAACTCCTC GGCTGTGACCCTCAC TCTTGTACATTCGCA GCATCGAACTCCTCT GCTGTGACCCTCACC CTTGTACATTCGCAC CATCGAACTCCTCTT CTGTGACCCTCACCA TTGTACATTCGCACC ATCGAACTCCTCTTC TGTGACCCTCACCAT TGTACATTCGCACCA TCGAACTCCTCTTCT GTGACCCTCACCATG GTACATTCGCACCAA CGAACTCCTCTTCTC TGACCCTCACCATGG TACATTCGCACCAAT GAACTCCTCTTCTCA GACCCTCACCATGGT ACATTCGCACCAATG AACTCCTCTTCTCAG ACCCTCACCATGGTG CATTCGCACCAATGC ACTCCTCTTCTCAGT CCCTCACCATGGTGG ATTCGCACCAATGCT CTCCTCTTCTCAGTT CCTCACCATGGTGGA TTCGCACCAATGCTT TCCTCTTCTCAGTTA CTCACCATGGTGGAG TCGCACCAATGCTTC CCTCTTCTCAGTTAA TCACCATGGTGGAGA CGCACCAATGCTTCA CTCTTCTCAGTTAAT CACCATGGTGGAGAA GCACCAATGCTTCAG TCTTCTCAGTTAATC ACCATGGTGGAGAAC CACCAATGCTTCAGT CTTCTCAGTTAATCG CCATGGTGGAGAACG ACCAATGCTTCAGTT TTCTCAGTTAATCGT CATGGTGGAGAACGA CCAATGCTTCAGTTC TCTCAGTTAATCGTG ATGGTGGAGAACGAC CAATGCTTCAGTTCC CTCAGTTAATCGTGA TGGTGGAGAACGACC AATGCTTCAGTTCCT TCAGTTAATCGTGAA GGTGGAGAACGACCA ATGCTTCAGTTCCTT CAGTTAATCGTGAAG GTGGAGAACGACCAT TGCTTCAGTTCCTTC AGTTAATCGTGAAGT TGGAGAACGACCATA GCTTCAGTTCCTTCC GTTAATCGTGAAGTG GGAGAACGACCATAT CTTCAGTTCCTTCCA TTAATCGTGAAGTGG GAGAACGACCATATC TTCAGTTCCTTCCAT TAATCGTGAAGTGGA AGAACGACCATATCC TCAGTTCCTTCCATT AATCGTGAAGTGGAA GAACGACCATATCCG CAGTTCCTTCCATTC ATCGTGAAGTGGAAC AACGACCATATCCGT AGTTCCTTCCATTCC TCGTGAAGTGGAACC ACGACCATATCCGTG GTTCCTTCCATTCCC CGTGAAGTGGAACCC GTGAAGTGGAACCCT CTGGCAGCGGCAGCC ACAAAATCCCCATCA TGAAGTGGAACCCTC TGGCAGCGGCAGCCT CAAAATCCCCATCAG GAAGTGGAACCCTCC GGCAGCGGCAGCCTC AAAATCCCCATCAGG AAGTGGAACCCTCCC GCAGCGGCAGCCTCA AAATCCCCATCAGGA AGTGGAACCCTCCCT CAGCGGCAGCCTCAG AATCCCCATCAGGAA GTGGAACCCTCCCTC AGCGGCAGCCTCAGG ATCCCCATCAGGAAG TGGAACCCTCCCTCT GCGGCAGCCTCAGGA TCCCCATCAGGAAGT GGAACCCTCCCTCTC CGGCAGCCTCAGGAC CCCCATCAGGAAGTA GAACCCTCCCTCTCT GGCAGCCTCAGGACG CCCATCAGGAAGTAT AACCCTCCCTCTCTG GCAGCCTCAGGACGG CCATCAGGAAGTATG ACCCTCCCTCTCTGC CAGCCTCAGGACGGC CATCAGGAAGTATGC CCCTCCCTCTCTGCC AGCCTCAGGACGGCT ATCAGGAAGTATGCC CCTCCCTCTCTGCCC GCCTCAGGACGGCTA TCAGGAAGTATGCCG CTCCCTCTCTGCCCA CCTCAGGACGGCTAC CAGGAAGTATGCCGA TCCCTCTCTGCCCAA CTCAGGACGGCTACC AGGAAGTATGCCGAC CCCTCTCTGCCCAAC TCAGGACGGCTACCT GGAAGTATGCCGACG CCTCTCTGCCCAACG CAGGACGGCTACCTT GAAGTATGCCGACGG CTCTCTGCCCAACGG AGGACGGCTACCTTT AAGTATGCCGACGGC TCTCTGCCCAACGGC GGACGGCTACCTTTA AGTATGCCGACGGCA CTCTGCCCAACGGCA GACGGCTACCTTTAC GTATGCCGACGGCAC TCTGCCCAACGGCAA ACGGCTACCTTTACC TATGCCGACGGCACC CTGCCCAACGGCAAC CGGCTACCTTTACCG ATGCCGACGGCACCA TGCCCAACGGCAACC GGCTACCTTTACCGG TGCCGACGGCACCAT GCCCAACGGCAACCT GCTACCTTTACCGGC GCCGACGGCACCATC CCCAACGGCAACCTG CTACCTTTACCGGCA CCGACGGCACCATCG CCAACGGCAACCTGA TACCTTTACCGGCAC CGACGGCACCATCGA CAACGGCAACCTGAG ACCTTTACCGGCACA GACGGCACCATCGAC AACGGCAACCTGAGT CCTTTACCGGCACAA ACGGCACCATCGACA ACGGCAACCTGAGTT CTTTACCGGCACAAT CGGCACCATCGACAT CGGCAACCTGAGTTA TTTACCGGCACAATT GGCACCATCGACATT GGCAACCTGAGTTAC TTACCGGCACAATTA GCACCATCGACATTG GCAACCTGAGTTACT TACCGGCACAATTAC CACCATCGACATTGA CAACCTGAGTTACTA ACCGGCACAATTACT ACCATCGACATTGAG AACCTGAGTTACTAC CCGGCACAATTACTG CCATCGACATTGAGG ACCTGAGTTACTACA CGGCACAATTACTGC CATCGACATTGAGGA CCTGAGTTACTACAT GGCACAATTACTGCT ATCGACATTGAGGAG CTGAGTTACTACATT GCACAATTACTGCTC TCGACATTGAGGAGG TGAGTTACTACATTG CACAATTACTGCTCC CGACATTGAGGAGGT GAGTTACTACATTGT ACAATTACTGCTCCA GACATTGAGGAGGTC AGTTACTACATTGTG CAATTACTGCTCCAA ACATTGAGGAGGTCA GTTACTACATTGTGC AATTACTGCTCCAAA CATTGAGGAGGTCAC TTACTACATTGTGCG ATTACTGCTCCAAAG ATTGAGGAGGTCACA TACTACATTGTGCGC TTACTGCTCCAAAGA TTGAGGAGGTCACAG ACTACATTGTGCGCT TACTGCTCCAAAGAC TGAGGAGGTCACAGA CTACATTGTGCGCTG ACTGCTCCAAAGACA GAGGAGGTCACAGAG TACATTGTGCGCTGG CTGCTCCAAAGACAA AGGAGGTCACAGAGA ACATTGTGCGCTGGC TGCTCCAAAGACAAA GGAGGTCACAGAGAA CATTGTGCGCTGGCA GCTCCAAAGACAAAA GAGGTCACAGAGAAC ATTGTGCGCTGGCAG CTCCAAAGACAAAAT AGGTCACAGAGAACC TTGTGCGCTGGCAGC TCCAAAGACAAAATC GGTCACAGAGAACCC TGTGCGCTGGCAGCG CCAAAGACAAAATCC GTCACAGAGAACCCC GTGCGCTGGCAGCGG CAAAGACAAAATCCC TCACAGAGAACCCCA TGCGCTGGCAGCGGC AAAGACAAAATCCCC CACAGAGAACCCCAA GCGCTGGCAGCGGCA AAGACAAAATCCCCA ACAGAGAACCCCAAG CGCTGGCAGCGGCAG AGACAAAATCCCCAT CAGAGAACCCCAAGA GCTGGCAGCGGCAGC GACAAAATCCCCATC AGAGAACCCCAAGAC GAGAACCCCAAGACT CAAAACTGAAGCCGA TTGAGAATTTCCTGC AGAACCCCAAGACTG AAAACTGAAGCCGAG TGAGAATTTCCTGCA GAACCCCAAGACTGA AAACTGAAGCCGAGA GAGAATTTCCTGCAC AACCCCAAGACTGAG AACTGAAGCCGAGAA AGAATTTCCTGCACA ACCCCAAGACTGAGG ACTGAAGCCGAGAAG GAATTTCCTGCACAA CCCCAAGACTGAGGT CTGAAGCCGAGAAGC AATTTCCTGCACAAC CCCAAGACTGAGGTG TGAAGCCGAGAAGCA ATTTCCTGCACAACT CCAAGACTGAGGTGT GAAGCCGAGAAGCAG TTTCCTGCACAACTC CAAGACTGAGGTGTG AAGCCGAGAAGCAGG TTCCTGCACAACTCC AAGACTGAGGTGTGT AGCCGAGAAGCAGGC TCCTGCACAACTCCA AGACTGAGGTGTGTG GCCGAGAAGCAGGCC CCTGCACAACTCCAT GACTGAGGTGTGTGG CCGAGAAGCAGGCCG CTGCACAACTCCATC ACTGAGGTGTGTGGT CGAGAAGCAGGCCGA TGCACAACTCCATCT CTGAGGTGTGTGGTG GAGAAGCAGGCCGAG GCACAACTCCATCTT TGAGGTGTGTGGTGG AGAAGCAGGCCGAGA CACAACTCCATCTTC GAGGTGTGTGGTGGG GAAGCAGGCCGAGAA ACAACTCCATCTTCG AGGTGTGTGGTGGGG AAGCAGGCCGAGAAG CAACTCCATCTTCGT GGTGTGTGGTGGGGA AGCAGGCCGAGAAGG AACTCCATCTTCGTG GTGTGTGGTGGGGAG GCAGGCCGAGAAGGA ACTCCATCTTCGTGC TGTGTGGTGGGGAGA CAGGCCGAGAAGGAG CTCCATCTTCGTGCC GTGTGGTGGGGAGAA AGGCCGAGAAGGAGG TCCATCTTCGTGCCC TGTGGTGGGGAGAAA GGCCGAGAAGGAGGA CCATCTTCGTGCCCA GTGGTGGGGAGAAAG GCCGAGAAGGAGGAG CATCTTCGTGCCCAG TGGTGGGGAGAAAGG CCGAGAAGGAGGAGG ATCTTCGTGCCCAGA GGTGGGGAGAAAGGG CGAGAAGGAGGAGGC TCTTCGTGCCCAGAC GTGGGGAGAAAGGGC GAGAAGGAGGAGGCT CTTCGTGCCCAGACC TGGGGAGAAAGGGCC AGAAGGAGGAGGCTG TTCGTGCCCAGACCT GGGGAGAAAGGGCCT GAAGGAGGAGGCTGA TCGTGCCCAGACCTG GGGAGAAAGGGCCTT AAGGAGGAGGCTGAA CGTGCCCAGACCTGA GGAGAAAGGGCCTTG AGGAGGAGGCTGAAT GTGCCCAGACCTGAA GAGAAAGGGCCTTGC GGAGGAGGCTGAATA TGCCCAGACCTGAAA AGAAAGGGCCTTGCT GAGGAGGCTGAATAC GCCCAGACCTGAAAG GAAAGGGCCTTGCTG AGGAGGCTGAATACC CCCAGACCTGAAAGG AAAGGGCCTTGCTGC GGAGGCTGAATACCG CCAGACCTGAAAGGA AAGGGCCTTGCTGCG GAGGCTGAATACCGC CAGACCTGAAAGGAA AGGGCCTTGCTGCGC AGGCTGAATACCGCA AGACCTGAAAGGAAG GGGCCTTGCTGCGCC GGCTGAATACCGCAA GACCTGAAAGGAAGC GGCCTTGCTGCGCCT GCTGAATACCGCAAA ACCTGAAAGGAAGCG GCCTTGCTGCGCCTG CTGAATACCGCAAAG CCTGAAAGGAAGCGG CCTTGCTGCGCCTGC TGAATACCGCAAAGT CTGAAAGGAAGCGGA CTTGCTGCGCCTGCC GAATACCGCAAAGTC TGAAAGGAAGCGGAG TTGCTGCGCCTGCCC AATACCGCAAAGTCT GAAAGGAAGCGGAGA TGCTGCGCCTGCCCC ATACCGCAAAGTCTT AAAGGAAGCGGAGAG GCTGCGCCTGCCCCA TACCGCAAAGTCTTT AAGGAAGCGGAGAGA CTGCGCCTGCCCCAA ACCGCAAAGTCTTTG AGGAAGCGGAGAGAT TGCGCCTGCCCCAAA CCGCAAAGTCTTTGA GGAAGCGGAGAGATG GCGCCTGCCCCAAAA CGCAAAGTCTTTGAG GAAGCGGAGAGATGT CGCCTGCCCCAAAAC GCAAAGTCTTTGAGA AAGCGGAGAGATGTC GCCTGCCCCAAAACT CAAAGTCTTTGAGAA AGCGGAGAGATGTCA CCTGCCCCAAAACTG AAAGTCTTTGAGAAT GCGGAGAGATGTCAT CTGCCCCAAAACTGA AAGTCTTTGAGAATT CGGAGAGATGTCATG TGCCCCAAAACTGAA AGTCTTTGAGAATTT GGAGAGATGTCATGC GCCCCAAAACTGAAG GTCTTTGAGAATTTC GAGAGATGTCATGCA CCCCAAAACTGAAGC TCTTTGAGAATTTCC AGAGATGTCATGCAA CCCAAAACTGAAGCC CTTTGAGAATTTCCT GAGATGTCATGCAAG CCAAAACTGAAGCCG TTTGAGAATTTCCTG AGATGTCATGCAAGT GATGTCATGCAAGTG CGCAGACACCTACAA TTGAGAGCAGAGTGG ATGTCATGCAAGTGG GCAGACACCTACAAC TGAGAGCAGAGTGGA TGTCATGCAAGTGGC CAGACACCTACAACA GAGAGCAGAGTGGAT GTCATGCAAGTGGCC AGACACCTACAACAT AGAGCAGAGTGGATA TCATGCAAGTGGCCA GACACCTACAACATC GAGCAGAGTGGATAA CATGCAAGTGGCCAA ACACCTACAACATCA AGCAGAGTGGATAAC ATGCAAGTGGCCAAC CACCTACAACATCAC GCAGAGTGGATAACA TGCAAGTGGCCAACA ACCTACAACATCACC CAGAGTGGATAACAA GCAAGTGGCCAACAC CCTACAACATCACCG AGAGTGGATAACAAG CAAGTGGCCAACACC CTACAACATCACCGA GAGTGGATAACAAGG AAGTGGCCAACACCA TACAACATCACCGAC AGTGGATAACAAGGA AGTGGCCAACACCAC ACAACATCACCGACC GTGGATAACAAGGAG GTGGCCAACACCACC CAACATCACCGACCC TGGATAACAAGGAGA TGGCCAACACCACCA AACATCACCGACCCG GGATAACAAGGAGAG GGCCAACACCACCAT ACATCACCGACCCGG GATAACAAGGAGAGA GCCAACACCACCATG CATCACCGACCCGGA ATAACAAGGAGAGAA CCAACACCACCATGT ATCACCGACCCGGAA TAACAAGGAGAGAAC CAACACCACCATGTC TCACCGACCCGGAAG AACAAGGAGAGAACT AACACCACCATGTCC CACCGACCCGGAAGA ACAAGGAGAGAACTG ACACCACCATGTCCA ACCGACCCGGAAGAG CAAGGAGAGAACTGT CACCACCATGTCCAG CCGACCCGGAAGAGC AAGGAGAGAACTGTC ACCACCATGTCCAGC CGACCCGGAAGAGCT AGGAGAGAACTGTCA CCACCATGTCCAGCC GACCCGGAAGAGCTG GGAGAGAACTGTCAT CACCATGTCCAGCCG ACCCGGAAGAGCTGG GAGAGAACTGTCATT ACCATGTCCAGCCGA CCCGGAAGAGCTGGA AGAGAACTGTCATTT CCATGTCCAGCCGAA CCGGAAGAGCTGGAG GAGAACTGTCATTTC CATGTCCAGCCGAAG CGGAAGAGCTGGAGA AGAACTGTCATTTCT ATGTCCAGCCGAAGC GGAAGAGCTGGAGAC GAACTGTCATTTCTA TGTCCAGCCGAAGCA GAAGAGCTGGAGACA AACTGTCATTTCTAA GTCCAGCCGAAGCAG AAGAGCTGGAGACAG ACTGTCATTTCTAAC TCCAGCCGAAGCAGG AGAGCTGGAGACAGA CTGTCATTTCTAACC CCAGCCGAAGCAGGA GAGCTGGAGACAGAG TGTCATTTCTAACCT CAGCCGAAGCAGGAA AGCTGGAGACAGAGT GTCATTTCTAACCTT AGCCGAAGCAGGAAC GCTGGAGACAGAGTA TCATTTCTAACCTTC GCCGAAGCAGGAACA CTGGAGACAGAGTAC CATTTCTAACCTTCG CCGAAGCAGGAACAC TGGAGACAGAGTACC ATTTCTAACCTTCGG CGAAGCAGGAACACC GGAGACAGAGTACCC TTTCTAACCTTCGGC GAAGCAGGAACACCA GAGACAGAGTACCCT TTCTAACCTTCGGCC AAGCAGGAACACCAC AGACAGAGTACCCTT TCTAACCTTCGGCCT AGCAGGAACACCACG GACAGAGTACCCTTT CTAACCTTCGGCCTT GCAGGAACACCACGG ACAGAGTACCCTTTC TAACCTTCGGCCTTT CAGGAACACCACGGC CAGAGTACCCTTTCT AACCTTCGGCCTTTC AGGAACACCACGGCC AGAGTACCCTTTCTT ACCTTCGGCCTTTCA GGAACACCACGGCCG GAGTACCCTTTCTTT CCTTCGGCCTTTCAC GAACACCACGGCCGC AGTACCCTTTCTTTG CTTCGGCCTTTCACA AACACCACGGCCGCA GTACCCTTTCTTTGA TTCGGCCTTTCACAT ACACCACGGCCGCAG TACCCTTTCTTTGAG TCGGCCTTTCACATT CACCACGGCCGCAGA ACCCTTTCTTTGAGA CGGCCTTTCACATTG ACCACGGCCGCAGAC CCCTTTCTTTGAGAG GGCCTTTCACATTGT CCACGGCCGCAGACA CCTTTCTTTGAGAGC GCCTTTCACATTGTA CACGGCCGCAGACAC CTTTCTTTGAGAGCA CCTTTCACATTGTAC ACGGCCGCAGACACC TTTCTTTGAGAGCAG CTTTCACATTGTACC CGGCCGCAGACACCT TTCTTTGAGAGCAGA TTTCACATTGTACCG GGCCGCAGACACCTA TCTTTGAGAGCAGAG TTCACATTGTACCGC GCCGCAGACACCTAC CTTTGAGAGCAGAGT TCACATTGTACCGCA CCGCAGACACCTACA TTTGAGAGCAGAGTG CACATTGTACCGCAT ACATTGTACCGCATC CAGCGCCTCCAACTT TTCCTGGGCCAGTGA CATTGTACCGCATCG AGCGCCTCCAACTTC TCCTGGGCCAGTGAC ATTGTACCGCATCGA GCGCCTCCAACTTCG CCTGGGCCAGTGACC TTGTACCGCATCGAT CGCCTCCAACTTCGT CTGGGCCAGTGACCT TGTACCGCATCGATA GCCTCCAACTTCGTC TGGGCCAGTGACCTG GTACCGCATCGATAT CCTCCAACTTCGTCT GGGCCAGTGACCTGG TACCGCATCGATATC CTCCAACTTCGTCTT GGCCAGTGACCTGGG ACCGCATCGATATCC TCCAACTTCGTCTTT GCCAGTGACCTGGGA CCGCATCGATATCCA CCAACTTCGTCTTTG CCAGTGACCTGGGAG CGCATCGATATCCAC CAACTTCGTCTTTGC CAGTGACCTGGGAGC GCATCGATATCCACA AACTTCGTCTTTGCA AGTGACCTGGGAGCC CATCGATATCCACAG ACTTCGTCTTTGCAA GTGACCTGGGAGCCA ATCGATATCCACAGC CTTCGTCTTTGCAAG TGACCTGGGAGCCAA TCGATATCCACAGCT TTCGTCTTTGCAAGG GACCTGGGAGCCAAG CGATATCCACAGCTG TCGTCTTTGCAAGGA ACCTGGGAGCCAAGG GATATCCACAGCTGC CGTCTTTGCAAGGAC CCTGGGAGCCAAGGC ATATCCACAGCTGCA GTCTTTGCAAGGACT CTGGGAGCCAAGGCC TATCCACAGCTGCAA TCTTTGCAAGGACTA TGGGAGCCAAGGCCT ATCCACAGCTGCAAC CTTTGCAAGGACTAT GGGAGCCAAGGCCTG TCCACAGCTGCAACC TTTGCAAGGACTATG GGAGCCAAGGCCTGA CCACAGCTGCAACCA TTGCAAGGACTATGC GAGCCAAGGCCTGAA CACAGCTGCAACCAC TGCAAGGACTATGCC AGCCAAGGCCTGAAA ACAGCTGCAACCACG GCAAGGACTATGCCC GCCAAGGCCTGAAAA CAGCTGCAACCACGA CAAGGACTATGCCCG CCAAGGCCTGAAAAC AGCTGCAACCACGAG AAGGACTATGCCCGC CAAGGCCTGAAAACT GCTGCAACCACGAGG AGGACTATGCCCGCA AAGGCCTGAAAACTC CTGCAACCACGAGGC GGACTATGCCCGCAG AGGCCTGAAAACTCC TGCAACCACGAGGCT GACTATGCCCGCAGA GGCCTGAAAACTCCA GCAACCACGAGGCTG ACTATGCCCGCAGAA GCCTGAAAACTCCAT CAACCACGAGGCTGA CTATGCCCGCAGAAG CCTGAAAACTCCATC AACCACGAGGCTGAG TATGCCCGCAGAAGG CTGAAAACTCCATCT ACCACGAGGCTGAGA ATGCCCGCAGAAGGA TGAAAACTCCATCTT CCACGAGGCTGAGAA TGCCCGCAGAAGGAG GAAAACTCCATCTTT CACGAGGCTGAGAAG GCCCGCAGAAGGAGC AAAACTCCATCTTTT ACGAGGCTGAGAAGC CCCGCAGAAGGAGCA AAACTCCATCTTTTT CGAGGCTGAGAAGCT CCGCAGAAGGAGCAG AACTCCATCTTTTTA GAGGCTGAGAAGCTG CGCAGAAGGAGCAGA ACTCCATCTTTTTAA AGGCTGAGAAGCTGG GCAGAAGGAGCAGAT CTCCATCTTTTTAAA GGCTGAGAAGCTGGG CAGAAGGAGCAGATG TCCATCTTTTTAAAG GCTGAGAAGCTGGGC AGAAGGAGCAGATGA CCATCTTTTTAAAGT CTGAGAAGCTGGGCT GAAGGAGCAGATGAC CATCTTTTTAAAGTG TGAGAAGCTGGGCTG AAGGAGCAGATGACA ATCTTTTTAAAGTGG GAGAAGCTGGGCTGC AGGAGCAGATGACAT TCTTTTTAAAGTGGC AGAAGCTGGGCTGCA GGAGCAGATGACATT CTTTTTAAAGTGGCC GAAGCTGGGCTGCAG GAGCAGATGACATTC TTTTTAAAGTGGCCG AAGCTGGGCTGCAGC AGCAGATGACATTCC TTTTAAAGTGGCCGG AGCTGGGCTGCAGCG GCAGATGACATTCCT TTTAAAGTGGCCGGA GCTGGGCTGCAGCGC CAGATGACATTCCTG TTAAAGTGGCCGGAA CTGGGCTGCAGCGCC AGATGACATTCCTGG TAAAGTGGCCGGAAC TGGGCTGCAGCGCCT GATGACATTCCTGGG AAAGTGGCCGGAACC GGGCTGCAGCGCCTC ATGACATTCCTGGGC AAGTGGCCGGAACCT GGCTGCAGCGCCTCC TGACATTCCTGGGCC AGTGGCCGGAACCTG GCTGCAGCGCCTCCA GACATTCCTGGGCCA GTGGCCGGAACCTGA CTGCAGCGCCTCCAA ACATTCCTGGGCCAG TGGCCGGAACCTGAG TGCAGCGCCTCCAAC CATTCCTGGGCCAGT GGCCGGAACCTGAGA GCAGCGCCTCCAACT ATTCCTGGGCCAGTG GCCGGAACCTGAGAA CCGGAACCTGAGAAT ACAAGTTGAGGATCA GGGCCAAGCTAAACC CGGAACCTGAGAATC CAAGTTGAGGATCAG GGCCAAGCTAAACCG GGAACCTGAGAATCC AAGTTGAGGATCAGC GCCAAGCTAAACCGG GAACCTGAGAATCCC AGTTGAGGATCAGCG CCAAGCTAAACCGGC AACCTGAGAATCCCA GTTGAGGATCAGCGA CAAGCTAAACCGGCT ACCTGAGAATCCCAA TTGAGGATCAGCGAG AAGCTAAACCGGCTA CCTGAGAATCCCAAT TGAGGATCAGCGAGA AGCTAAACCGGCTAA CTGAGAATCCCAATG GAGGATCAGCGAGAA GCTAAACCGGCTAAA TGAGAATCCCAATGG AGGATCAGCGAGAAT CTAAACCGGCTAAAC GAGAATCCCAATGGA GGATCAGCGAGAATG TAAACCGGCTAAACC AGAATCCCAATGGAT GATCAGCGAGAATGT AAACCGGCTAAACCC GAATCCCAATGGATT ATCAGCGAGAATGTG AACCGGCTAAACCCG AATCCCAATGGATTG TCAGCGAGAATGTGT ACCGGCTAAACCCGG ATCCCAATGGATTGA CAGCGAGAATGTGTG CCGGCTAAACCCGGG TCCCAATGGATTGAT AGCGAGAATGTGTGT CGGCTAAACCCGGGG CCCAATGGATTGATT GCGAGAATGTGTGTC GGCTAAACCCGGGGA CCAATGGATTGATTC CGAGAATGTGTGTCC GCTAAACCCGGGGAA CAATGGATTGATTCT GAGAATGTGTGTCCA CTAAACCCGGGGAAC AATGGATTGATTCTA AGAATGTGTGTCCAG TAAACCCGGGGAACT ATGGATTGATTCTAA GAATGTGTGTCCAGA AAACCCGGGGAACTA TGGATTGATTCTAAT AATGTGTGTCCAGAC AACCCGGGGAACTAC GGATTGATTCTAATG ATGTGTGTCCAGACA ACCCGGGGAACTACA GATTGATTCTAATGT TGTGTGTCCAGACAG CCCGGGGAACTACAC ATTGATTCTAATGTA GTGTGTCCAGACAGG CCGGGGAACTACACA TTGATTCTAATGTAT TGTGTCCAGACAGGA CGGGGAACTACACAG TGATTCTAATGTATG GTGTCCAGACAGGAA GGGGAACTACACAGC GATTCTAATGTATGA TGTCCAGACAGGAAT GGGAACTACACAGCC ATTCTAATGTATGAA GTCCAGACAGGAATA GGAACTACACAGCCC TTCTAATGTATGAAA TCCAGACAGGAATAC GAACTACACAGCCCG TCTAATGTATGAAAT CCAGACAGGAATACA AACTACACAGCCCGG CTAATGTATGAAATA CAGACAGGAATACAG ACTACACAGCCCGGA TAATGTATGAAATAA AGACAGGAATACAGG CTACACAGCCCGGAT AATGTATGAAATAAA GACAGGAATACAGGA TACACAGCCCGGATT ATGTATGAAATAAAA ACAGGAATACAGGAA ACACAGCCCGGATTC TGTATGAAATAAAAT CAGGAATACAGGAAG CACAGCCCGGATTCA GTATGAAATAAAATA AGGAATACAGGAAGT ACAGCCCGGATTCAG TATGAAATAAAATAC GGAATACAGGAAGTA CAGCCCGGATTCAGG ATGAAATAAAATACG GAATACAGGAAGTAT AGCCCGGATTCAGGC TGAAATAAAATACGG AATACAGGAAGTATG GCCCGGATTCAGGCC GAAATAAAATACGGA ATACAGGAAGTATGG CCCGGATTCAGGCCA AAATAAAATACGGAT TACAGGAAGTATGGA CCGGATTCAGGCCAC AATAAAATACGGATC ACAGGAAGTATGGAG CGGATTCAGGCCACA ATAAAATACGGATCA CAGGAAGTATGGAGG GGATTCAGGCCACAT TAAAATACGGATCAC AGGAAGTATGGAGGG GATTCAGGCCACATC AAAATACGGATCACA GGAAGTATGGAGGGG ATTCAGGCCACATCT AAATACGGATCACAA GAAGTATGGAGGGGC TTCAGGCCACATCTC AATACGGATCACAAG AAGTATGGAGGGGCC TCAGGCCACATCTCT ATACGGATCACAAGT AGTATGGAGGGGCCA CAGGCCACATCTCTC TACGGATCACAAGTT GTATGGAGGGGCCAA AGGCCACATCTCTCT ACGGATCACAAGTTG TATGGAGGGGCCAAG GGCCACATCTCTCTC CGGATCACAAGTTGA ATGGAGGGGCCAAGC GCCACATCTCTCTCT GGATCACAAGTTGAG TGGAGGGGCCAAGCT CCACATCTCTCTCTG GATCACAAGTTGAGG GGAGGGGCCAAGCTA CACATCTCTCTCTGG ATCACAAGTTGAGGA GAGGGGCCAAGCTAA ACATCTCTCTCTGGG TCACAAGTTGAGGAT AGGGGCCAAGCTAAA CATCTCTCTCTGGGA CACAAGTTGAGGATC GGGGCCAAGCTAAAC ATCTCTCTCTGGGAA TCTCTCTCTGGGAAT AACAGGATATGAAAA TGATCGTGGGAGGGT CTCTCTCTGGGAATG ACAGGATATGAAAAC GATCGTGGGAGGGTT TCTCTCTGGGAATGG CAGGATATGAAAACT ATCGTGGGAGGGTTG CTCTCTGGGAATGGG AGGATATGAAAACTT TCGTGGGAGGGTTGG TCTCTGGGAATGGGT GGATATGAAAACTTC CGTGGGAGGGTTGGT CTCTGGGAATGGGTC GATATGAAAACTTCA GTGGGAGGGTTGGTG TCTGGGAATGGGTCG ATATGAAAACTTCAT TGGGAGGGTTGGTGA CTGGGAATGGGTCGT TATGAAAACTTCATC GGGAGGGTTGGTGAT TGGGAATGGGTCGTG ATGAAAACTTCATCC GGAGGGTTGGTGATT GGGAATGGGTCGTGG TGAAAACTTCATCCA GAGGGTTGGTGATTA GGAATGGGTCGTGGA GAAAACTTCATCCAT AGGGTTGGTGATTAT GAATGGGTCGTGGAC AAAACTTCATCCATC GGGTTGGTGATTATG AATGGGTCGTGGACA AAACTTCATCCATCT GGTTGGTGATTATGC ATGGGTCGTGGACAG AACTTCATCCATCTG GTTGGTGATTATGCT TGGGTCGTGGACAGA ACTTCATCCATCTGA TTGGTGATTATGCTG GGGTCGTGGACAGAT CTTCATCCATCTGAT TGGTGATTATGCTGT GGTCGTGGACAGATC TTCATCCATCTGATC GGTGATTATGCTGTA GTCGTGGACAGATCC TCATCCATCTGATCA GTGATTATGCTGTAC TCGTGGACAGATCCT CATCCATCTGATCAT TGATTATGCTGTACG CGTGGACAGATCCTG ATCCATCTGATCATC GATTATGCTGTACGT GTGGACAGATCCTGT TCCATCTGATCATCG ATTATGCTGTACGTC TGGACAGATCCTGTG CCATCTGATCATCGC TTATGCTGTACGTCT GGACAGATCCTGTGT CATCTGATCATCGCT TATGCTGTACGTCTT GACAGATCCTGTGTT ATCTGATCATCGCTC ATGCTGTACGTCTTC ACAGATCCTGTGTTC TCTGATCATCGCTCT TGCTGTACGTCTTCC CAGATCCTGTGTTCT CTGATCATCGCTCTG GCTGTACGTCTTCCA AGATCCTGTGTTCTT TGATCATCGCTCTGC CTGTACGTCTTCCAT GATCCTGTGTTCTTC GATCATCGCTCTGCC TGTACGTCTTCCATA ATCCTGTGTTCTTCT ATCATCGCTCTGCCC GTACGTCTTCCATAG TCCTGTGTTCTTCTA TCATCGCTCTGCCCG TACGTCTTCCATAGA CCTGTGTTCTTCTAT CATCGCTCTGCCCGT ACGTCTTCCATAGAA CTGTGTTCTTCTATG ATCGCTCTGCCCGTC CGTCTTCCATAGAAA TGTGTTCTTCTATGT TCGCTCTGCCCGTCG GTCTTCCATAGAAAG GTGTTCTTCTATGTC CGCTCTGCCCGTCGC TCTTCCATAGAAAGA TGTTCTTCTATGTCC GCTCTGCCCGTCGCT CTTCCATAGAAAGAG GTTCTTCTATGTCCA CTCTGCCCGTCGCTG TTCCATAGAAAGAGA TTCTTCTATGTCCAG TCTGCCCGTCGCTGT TCCATAGAAAGAGAA TCTTCTATGTCCAGG CTGCCCGTCGCTGTC CCATAGAAAGAGAAA CTTCTATGTCCAGGC TGCCCGTCGCTGTCC CATAGAAAGAGAAAT TTCTATGTCCAGGCC GCCCGTCGCTGTCCT ATAGAAAGAGAAATA TCTATGTCCAGGCCA CCCGTCGCTGTCCTG TAGAAAGAGAAATAA CTATGTCCAGGCCAA CCGTCGCTGTCCTGT AGAAAGAGAAATAAC TATGTCCAGGCCAAA CGTCGCTGTCCTGTT GAAAGAGAAATAACA ATGTCCAGGCCAAAA GTCGCTGTUCTGTTG AAAGAGAAATAACAG TGTCCAGGCCAAAAC TCGCTGTCCTGTTGA AAGAGAAATAACAGC GTCCAGGCCAAAACA CGCTGTCCTGTTGAT AGAGAAATAACAGCA TCCAGGCCAAAACAG GCTGTCCTGTTGATC GAGAAATAACAGCAG CCAGGCCAAAACAGG CTGTCCTGTTGATCG AGAAATAACAGCAGG CAGGCCAAAACAGGA TGTCCTGTTGATCGT GAAATAACAGCAGGC AGGCCAAAACAGGAT GTCCTGTTGATCGTG AAATAACAGCAGGCT GGCCAAAACAGGATA TCCTGTTGATCGTGG AATAACAGCAGGCTG GCCAAAACAGGATAT CCTGTTGATCGTGGG ATAACAGCAGGCTGG CCAAAACAGGATATG CTGTTGATCGTGGGA TAACAGCAGGCTGGG CAAAACAGGATATGA TGTTGATCGTGGGAG AACAGCAGGCTGGGG AAAACAGGATATGAA GTTGATCGTGGGAGG ACAGCAGGCTGGGGA AAACAGGATATGAAA TTGATCGTGGGAGGG CAGCAGGCTGGGGAA AGCAGGCTGGGGAAT TGCTGATGTGTACGT GCCGGGAACTTGGGC GCAGGCTGGGGAATG GCTGATGTGTACGTT CCGGGAACTTGGGCA CAGGCTGGGCAATGG CTGATGTGTACGTTC CGGGAACTTGGGCAG AGGCTGGGGAATGGA TGATGTGTACGTTCC GGGAACTTGGGCAGG GGCTGGGGAATGGAG GATGTGTACGTTCCT GGAACTTGGGCAGGG GCTGGGGAATGGAGT ATGTGTACGTTCCTG GAACTTGGGCAGGGG CTGGGGAATGGAGTG TGTGTACGTTCCTGA AACTTGGGCAGGGGT TGGGGAATGGAGTGC GTGTACGTTCCTGAT ACTTGGGCAGGGGTC GGGGAATGGAGTGCT TGTACGTTCCTGATG CTTGGGCAGGGGTCG GGGAATGGAGTGCTG GTACGTTCCTGATGA TTGGGCAGGGGTCGT GGAATGGAGTGCTGT TACGTTCCTGATGAG TGGGCAGGGGTCGTT GAATGGAGTGCTGTA ACGTTCCTGATGAGT GGGCAGGGGTCGTTT AATGGAGTGCTGTAT CGTTCCTGATGAGTG GGCAGGGGTCGTTTG ATGGAGTGCTGTATG GTTCCTGATGAGTGG GCAGGGGTCGTTTGG TGGAGTGCTGTATGC TTCCTGATGAGTGGG CAGGGGTCGTTTGGG GGAGTGCTGTATGCC TCCTGATGAGTGGGA AGGGGTCGTTTGGGA GAGTGCTGTATGCCT CCTGATGAGTGGGAG GGGGTCGTTTGGGAT AGTGCTGTATGCCTC CTGATGAGTGGGAGG GGGTCGTTTGGGATG GTGCTGTATGCCTCT TGATGAGTGGGAGGT GGTCGTTTGGGATGG TGCTGTATGCCTCTG GATGAGTGGGAGGTG GTCGTTTGGGATGGT GCTGTATGCCTCTGT ATGAGTGGGAGGTGG TCGTTTGGGATGGTC CTGTATGCCTCTGTG TGAGTGGGAGGTGGC CGTTTGGGATGGTCT TGTATGCCTCTGTGA GAGTGGGAGGTGGCT GTTTGGGATGGTCTA GTATGCCTCTGTGAA AGTGGGAGGTGGCTC TTTGGGATGGTCTAT TATGCCTCTGTGAAC GTGGGAGGTGGCTCG TTGGGATGGTCTATG ATGCCTCTGTGAACC TGGGAGGTGGCTCGG TGGGATGGTCTATGA TGCCTCTGTGAACCC GGGAGGTGGCTCGGG GGGATGGTCTATGAA GCCTCTGTGAACCCG GGAGGTGGCTCGGGA GGATGGTCTATGAAG CCTCTGTGAACCCGG GAGGTGGCTCGGGAG GATGGTCTATGAAGG CTCTGTGAACCCGGA AGGTGGCTCGGGAGA ATGGTCTATGAAGGA TCTGTGAACCCGGAG GGTGGCTCGGGAGAA TGGTCTATGAAGGAG CTGTGAACCCGGAGT GTGGCTCGGGAGAAG GGTCTATGAAGGAGT TGTGAACCCGGAGTA TGGCTCGGGAGAAGA GTCTATGAAGGAGTT GTGAACCCGGAGTAC GGCTCGGGAGAAGAT TCTATGAAGGAGTTG TGAACCCGGAGTACT GCTCGGGAGAAGATC CTATGAAGGAGTTGC GAACCCGGAGTACTT CTCGGGAGAAGATCA TATGAAGGAGTTGCC AACCCGGAGTACTTC TCGGGAGAAGATCAC ATGAAGGAGTTGCCA ACCCGGAGTACTTCA CGGGAGAAGATCACC TGAAGGAGTTGCCAA CCCGGAGTACTTCAG GGGAGAAGATCACCA GAAGGAGTTGCCAAG CCGGAGTACTTCAGC GGAGAAGATCACCAT AAGGAGTTGCCAAGG CGGAGTACTTCAGCG GAGAAGATCACCATG AGGAGTTGCCAAGGG GGAGTACTTCAGCGC AGAAGATCACCATGA GGAGTTGCCAAGGGT GAGTACTTCAGCGCT GAAGATCACCATGAG GAGTTGCCAAGGGTG AGTACTTCAGCGCTG AAGATCACCATGAGC AGTTGCCAAGGGTGT GTACTTCAGCGCTGC AGATCACCATGAGCC GTTGCCAAGGGTGTG TACTTCAGCGCTGCT GATCACCATGAGCCG TTGCCAAGGGTGTGG ACTTCAGCGCTGCTG ATCACCATGAGCCGG TGCCAAGGGTGTGGT CTTCAGCGCTGCTGA TCACCATGAGCCGGG GCCAAGGGTGTGGTG TTCAGCGCTGCTGAT CACCATGAGCCGGGA CCAAGGGTGTGGTGA TCAGCGCTGCTGATG ACCATGAGCCGGGAA CAAGGGTGTGGTGAA CAGCGCTGCTGATGT CCATGAGCCGGGAAC AAGGGTGTGGTGAAA AGCGCTGCTGATGTG CATGAGCCGGGAACT AGGGTGTGGTGAAAG GCGCTGCTGATGTGT ATGAGCCGGGAACTT GGGTGTGGTGAAAGA CGCTGCTGATGTGTA TGAGCCGGGAACTTG GGTGTGGTGAAAGAT GCTGCTGATGTGTAC GAGCCGGGAACTTGG GTGTGGTGAAAGATG CTGCTGATGTGTACG AGCCGGGAACTTGGG TGTGGTGAAAGATGA GTGGTGAAAGATCAA AAGCATGCGTGAGAG ATTGTCACCATGTGG TGGTGAAAGATGAAC AGCATGCGTGAGAGG TTGTCACCATGTGGT GGTGAAAGATGAACC GCATGCGTGAGAGGA TGTCACCATGTGGTG GTGAAAGATGAACCT CATGCGTGAGAGGAT GTCACCATGTGGTGC TGAAAGATGAACCTG ATGCGTGAGAGGATT TCACCATGTGGTGCG GAAAGATGAACCTGA TGCGTGAGAGGATTG CACCATGTGGTGCGA AAAGATGAACCTGAA GCGTGAGAGGATTGA ACCATGTGGTGCGAT AAGATGAACCTGAAA CGTGAGAGGATTGAG CCATGTGGTGCGATT AGATGAACCTGAAAC GTGAGAGGATTGAGT CATGTGGTGCGATTG GATGAACCTGAAACC TGAGAGGATTGAGTT ATGTGGTGCGATTGC ATGAACCTGAAACCA GAGAGGATTGAGTTT TGTGGTGCGATTGCT TGAACCTGAAACCAG AGAGGATTGAGTTTC GTGGTGCGATTGCTG GAACCTGAAACCAGA GAGGATTGAGTTTCT TGGTGCGATTGCTGG AACCTGAAACCAGAG AGGATTGAGTTTCTC GGTGCGATTGCTGGG ACCTGAAACCAGAGT GGATTGAGTTTCTCA GTGCGATTGCTGGGT CCTGAAACCAGAGTG GATTGAGTTTCTCAA TGCGATTGCTGGGTG CTGAAACCAGAGTGG ATTGAGTTTCTCAAC GCGATTGCTGGGTGT TGAAACCAGAGTGGC TTGAGTTTCTCAACG CGATTGCTGGGTGTG GAAACCAGAGTGGCC TGAGTTTCTCAACGA GATTGCTGGGTGTGG AAACCAGAGTGGCCA GAGTTTCTCAACGAA ATTGCTGGGTGTGGT AACCAGAGTGGCCAT AGTTTCTCAACGAAG TTGCTGGGTGTGGTG ACCAGAGTGGCCATT GTTTCTCAACGAAGC TGCTGGGTGTGGTGT CCAGAGTGGCCATTA TTTCTCAACGAAGCT GCTGGGTGTGGTGTC CAGAGTGGCCATTAA TTCTCAACGAAGCTT CTGGGTGTGGTGTCC AGAGTGGCCATTAAA TCTCAACGAAGCTTC TGGGTGTGGTGTCCC GAGTGGCCATTAAAA CTCAACGAAGCTTCT GGGTGTGGTGTCCCA AGTGGCCATTAAAAC TCAACGAAGCTTCTG GGTGTGGTGTCCCAA GTGGCCATTAAAACA CAACGAAGCTTCTGT GTGTGGTGTCCCAAG TGGCCATTAAAACAG AACGAAGCTTCTGTG TGTGGTGTCCCAAGG GGCCATTAAAACAGT ACGAAGCTTCTGTGA GTGGTGTCCCAAGGC GCCATTAAAACAGTG CGAAGCTTCTGTGAT TGGTGTCCCAAGGCC CCATTAAAACAGTGA GAAGCTTCTGTGATG GGTGTCCCAAGGCCA CATTAAAACAGTGAA AAGCTTCTGTGATGA GTGTCCCAAGGCCAG ATTAAAACAGTGAAC AGCTTCTGTGATGAA TGTCCCAAGGCCAGC TTAAAACAGTGAACG GCTTCTGTGATGAAG GTCCCAAGGCCAGCC TAAAACAGTGAACGA CTTCTGTGATGAAGG TCCCAAGGCCAGCCA AAAACAGTGAACGAG TTCTGTGATGAAGGA CCCAAGGCCAGCCAA AAACAGTGAACGAGG TCTGTGATGAAGGAG CCAAGGCCAGCCAAC AACAGTGAACGAGGC CTGTGATGAAGGAGT CAAGGCCAGCCAACA ACAGTGAACGAGGCC TGTGATGAAGGAGTT AAGGCCAGCCAACAC CAGTGAACGAGGCCG GTGATGAAGGAGTTC AGGCCAGCCAACACT AGTGAACGAGGCCGC TGATGAAGGAGTTCA GGCCAGCCAACACTG GTGAACGAGGCCGCA GATGAAGGAGTTCAA GCCAGCCAACACTGG TGAACGAGGCCGCAA ATGAAGGAGTTCAAT CCAGCCAACACTGGT GAACGAGGCCGCAAG TGAAGGAGTTCAATT CAGCCAACACTGGTC AACGAGGCCGCAAGC GAAGGAGTTCAATTG AGCCAACACTGGTCA ACGAGGCCGCAAGCA AAGGAGTTCAATTGT GCCAACACTGGTCAT CGAGGCCGCAAGCAT AGGAGTTCAATTGTC CCAACACTGGTCATC GAGGCCGCAAGCATG GGAGTTCAATTGTCA CAACACTGGTCATCA AGGCCGCAAGCATGC GAGTTCAATTGTCAC AACACTGGTCATCAT GGCCGCAAGCATGCG AGTTCAATTGTCACC ACACTGGTCATCATG GCCGCAAGCATGCGT GTTCAATTGTCACCA CACTGGTCATCATGG CCGCAAGCATGCGTG TTCAATTGTCACCAT ACTGGTCATCATGGA CGCAAGCATGCGTGA TCAATTGTCACCATG CTGGTCATCATGGAA GCAAGCATGCGTGAG CAATTGTCACCATGT TGGTCATCATGGAAC CAAGCATGCGTGAGA AATTGTCACCATGTG GGTCATCATGGAACT GTCATCATGGAACTG GCCAGAAATGGAGAA AGATGGCCGGAGAGA TCATCATGGAACTGA CCAGAAATGGAGAAT GATGGCCGGAGAGAT CATCATGGAACTGAT CAGAAATGGAGAATA ATGGCCGGAGAGATT ATCATGGAACTGATG AGAAATGGAGAATAA TGGCCGGAGAGATTG TCATGGAACTGATGA GAAATGGAGAATAAT GGCCGGAGAGATTGC CATGGAACTGATGAC AAATGGAGAATAATC GCCGGAGAGATTGCA ATGGAACTGATGACA AATGGAGAATAATCC CCGGAGAGATTGCAG TGGAACTGATGACAC ATGGAGAATAATCCA CGGAGAGATTGCAGA GGAACTGATGACACG TGGAGAATAATCCAG GGAGAGATTGCAGAC GAACTGATGACACGG GGAGAATAATCCAGT GAGAGATTGCAGACG AACTGATGACACGGG GAGAATAATCCAGTC AGAGATTGCAGACGG ACTGATGACACGGGG AGAATAATCCAGTCC GAGATTGCAGACGGC CTGATGACACGGGGC GAATAATCCAGTCCT AGATTGCAGACGGCA TGATGACACGGGGCG AATAATCCAGTCCTA GATTGCAGACGGCAT GATGACACGGGGCGA ATAATCCAGTCCTAG ATTGCAGACGGCATG ATGACACGGGGCGAT TAATCCAGTCCTAGC TTGCAGACGGCATGG TGACACGGGGCGATC AATCCAGTCCTAGCA TGCAGACGGCATGGC GACACGGGGCGATCT ATCCAGTCCTAGCAC GCAGACGGCATGGCA ACACGGGGCGATCTC TCCAGTCCTAGCACC CAGACGGCATGGCAT CACGGGGCGATCTCA CCAGTCCTAGCACCT AGACGGCATGGCATA ACGGGGCGATCTCAA CAGTCCTAGCACCTC GACGGCATGGCATAC CGGGGCGATCTCAAA AGTCCTAGCACCTCC ACGGCATGGCATACC GGGGCGATCTCAAAA GTCCTAGCACCTCCA CGGCATGGCATACCT GGGCGATCTCAAAAG TCCTAGCACCTCCAA GGCATGGCATACCTC GGCGATCTCAAAAGT CCTAGCACCTCCAAG GCATGGCATACCTCA GCGATCTCAAAAGTT CTAGCACCTCCAAGC CATGGCATACCTCAA CGATCTCAAAAGTTA TAGCACCTCCAAGCC ATGGCATACCTCAAC GATCTCAAAAGTTAT AGCACCTCCAAGCCT TGGCATACCTCAACG ATCTCAAAAGTTATC GCACCTCCAAGCCTG GGCATACCTCAACGC TCTCAAAAGTTATCT CACCTCCAAGCCTGA GCATACCTCAACGCC CTCAAAAGTTATCTC ACCTCCAAGCCTGAG CATACCTCAACGCCA TCAAAAGTTATCTCC CCTCCAAGCCTGAGC ATACCTCAACGCCAA CAAAAGTTATCTCCG CTCCAAGCCTGAGCA TACCTCAACGCCAAT AAAAGTTATCTCCGG TCCAAGCCTGAGCAA ACCTCAACGCCAATA AAAGTTATCTCCGGT CCAAGCCTGAGCAAG CCTCAACGCCAATAA AAGTTATCTCCGGTC CAAGCCTGAGCAAGA CTCAACGCCAATAAG AGTTATCTCCGGTCT AAGCCTGAGCAAGAT TCAACGCCAATAAGT GTTATCTCCGGTCTC AGCCTGAGCAAGATG CAACGCCAATAAGTT TTATCTCCGGTCTCT GCCTGAGCAAGATGA AACGCCAATAAGTTC TATCTCCGGTCTCTG CCTGAGCAAGATGAT ACGCCAATAAGTTCG ATCTCCGGTCTCTGA CTGAGCAAGATGATT CGCCAATAAGTTCGT TCTCCGGTCTCTGAG TGAGCAAGATGATTC GCCAATAAGTTCGTC CTCCGGTCTCTGAGG GAGCAAGATGATTCA CCAATAAGTTCGTCC TCCGGTCTCTGAGGC AGCAAGATGATTCAG CAATAAGTTCGTCCA CCGGTCTCTGAGGCC GCAAGATGATTCAGA AATAAGTTCGTCCAC CGGTCTCTGAGGCCA CAAGATGATTCAGAT ATAAGTTCGTCCACA GGTCTCTGAGGCCAG AAGATGATTCAGATG TAAGTTCGTCCACAG GTCTCTGAGGCCAGA AGATGATTCAGATGG AAGTTCGTCCACAGA TCTCTGAGGCCAGAA GATGATTCAGATGGC AGTTCGTCCACAGAG CTCTGAGGCCAGAAA ATGATTCAGATGGCC GTTCGTCCACAGAGA TCTGAGGCCAGAAAT TGATTCAGATGGCCG TTCGTCCACAGAGAC CTGAGGCCAGAAATG GATTCAGATGGCCGG TCGTCCACAGAGACC TGAGGCCAGAAATGG ATTCAGATGGCCGGA CGTCCACAGAGACCT GAGGCCAGAAATGGA TTCAGATGGCCGGAG GTCCACAGAGACCTT AGGCCAGAAATGGAG TCAGATGGCCGGAGA TCCACAGAGACCTTG GGCCAGAAATGGAGA CAGATGGCCGGAGAG CCACAGAGACCTTGC CACAGAGACCTTGCT CGGAGATTTTGGTAT GCAAAGGGCTGCTGC ACAGAGACCTTGCTG GGAGATTTTGGTATG CAAAGGGCTGCTGCC CAGAGACCTTGCTGC GAGATTTTGGTATGA AAAGGGCTGCTGCCC AGAGACCTTGCTGCC AGATTTTGGTATGAC AAGGGCTGCTGCCCG GAGACCTTGCTGCCC GATTTTGGTATGACG AGGGCTGCTGCCCGT AGACCTTGCTGCCCG ATTTTGGTATGACGC GGGCTGCTGCCCGTG GACCTTGCTGCCCGG TTTTGGTATGACGCG GGCTGCTGCCCGTGC ACCTTGCTGCCCGGA TTTGGTATGACGCGA GCTGCTGCCCGTGCG CCTTGCTGCCCGGAA TTGGTATGACGCGAG CTGCTGCCCGTGCGC CTTGCTGCCCGGAAT TGGTATGACGCGAGA TGCTGCCCGTGCGCT TTGCTGCCCGGAATT GGTATGACGCGAGAT GCTGCCCGTGCGCTG TGCTGCCCGGAATTG GTATGACGCGAGATA CTGCCCGTGCGCTGG GCTGCCCGGAATTGC TATGACGCGAGATAT TGCCCGTGCGCTGGA CTGCCCGGAATTGCA ATGACGCGAGATATC GCCCGTGCGCTGGAT TGCCCGGAATTGCAT TGACGCGAGATATCT CCCGTGCGCTGGATG GCCCGGAATTGCATG GACGCGAGATATCTA CCGTGCGCTGGATGT CCCGGAATTGCATGG ACGCGAGATATCTAT CGTGCGCTGGATGTC CCGGAATTGCATGGT CGCGAGATATCTATG GTGCGCTGGATGTCT CGGAATTGCATGGTA GCGAGATATCTATGA TGCGCTGGATGTCTC GGAATTGCATGGTAG CGAGATATCTATGAG GCGCTGGATGTCTCC GAATTGCATGGTAGC GAGATATCTATGAGA CGCTGGATGTCTCCT AATTGCATGGTAGCC AGATATCTATGAGAC GCTGGATGTCTCCTG ATTGCATGGTAGCCG GATATCTATGAGACA CTGGATGTCTCCTGA TTGCATGGTAGCCGA ATATCTATGAGACAG TGGATGTCTCCTGAG TGCATGGTAGCCGAA TATCTATGAGACAGA GGATGTCTCCTGAGT GCATGGTAGCCGAAG ATCTATGAGACAGAC GATGTCTCCTGAGTC CATGGTAGCCGAAGA TCTATGAGACAGACT ATGTCTCCTGAGTCC ATGGTAGCCGAAGAT CTATGAGACAGACTA TGTCTCCTGAGTCCC TGGTAGCCGAAGATT TATGAGACAGACTAT GTCTCCTGAGTCCCT GGTAGCCGAAGATTT ATGAGACAGACTATT TCTCCTGAGTCCCTC GTAGCCGAAGATTTC TGAGACAGACTATTA CTCCTGAGTCCCTCA TAGCCGAAGATTTCA GAGACAGACTATTAC TCCTGAGTCCCTCAA AGCCGAAGATTTCAC AGACAGACTATTACC CCTGAGTCCCTCAAG GCCGAAGATTTCACA GACAGACTATTACCG CTGAGTCCCTCAAGG CCGAAGATTTCACAG ACAGACTATTACCGG TGAGTCCCTCAAGGA CGAAGATTTCACAGT CAGACTATTACCGGA GAGTCCCTCAAGGAT GAAGATTTCACAGTC AGACTATTACCGGAA AGTCCCTCAAGGATG AAGATTTCACAGTCA GACTATTACCGGAAA GTCCCTCAAGGATGG AGATTTCACAGTCAA ACTATTACCGGAAAG TCCCTCAAGGATGGA GATTTCACAGTCAAA CTATTACCGGAAAGG CCCTCAAGGATGGAG ATTTCACAGTCAAAA TATTACCGGAAAGGA CCTCAAGGATGGAGT TTTCACAGTCAAAAT ATTACCGGAAAGGAG CTCAAGGATGGAGTC TTCACAGTCAAAATC TTACCGGAAAGGAGG TCAAGGATGGAGTCT TCACAGTCAAAATCG TACCGGAAAGGAGGC CAAGGATGGAGTCTT CACAGTCAAAATCGG ACCGGAAAGGAGGCA AAGGATGGAGTCTTC ACAGTCAAAATCGGA CCGGAAAGGAGGCAA AGGATGGAGTCTTCA CAGTCAAAATCGGAG CGGAAAGGAGGCAAA GGATGGAGTCTTCAC AGTCAAAATCGGAGA GGAAAGGAGGCAAAG GATGGAGTCTTCACC GTCAAAATCGGAGAT GAAAGGAGGCAAAGG ATGGAGTCTTCACCA TCAAAATCGGAGATT AAAGGAGGCAAAGGG TGGAGTCTTCACCAC CAAAATCGGAGATTT AAGGAGGCAAAGGGC GGAGTCTTCACCACT AAAATCGGAGATTTT AGGAGGCAAAGGGCT GAGTCTTCACCACTT AAATCGGAGATTTTG GGAGGCAAAGGGCTG AGTCTTCACCACTTA AATCGGAGATTTTGG GAGGCAAAGGGCTGC GTCTTCACCACTTAC ATCGGAGATTTTGGT AGGCAAAGGGCTGCT TCTTCACCACTTACT TCGGAGATTTTGGTA GGCAAAGGGCTGCTG CTTCACCACTTACTC TTCACCACTTACTCG ACTGGCCGAGCAGCC TGGAGGGCGGCCTTC TCACCACTTACTCGG CTGGCCGAGCAGCCC GGAGGGCGGCCTTCT CACCACTTACTCGGA TGGCCGAGCAGCCCT GAGGGCGGCCTTCTG ACCACTTACTCGGAC GGCCGAGCAGCCCTA AGGGCGGCCTTCTGG CCACTTACTCGGACG GCCGAGCAGCCCTAC GGGCGGCCTTCTGGA CACTTACTCGGACGT CCGAGCAGCCCTACC GGCGGCCTTCTGGAC ACTTACTCGGACGTC CGAGCAGCCCTACCA GCGGCCTTCTGGACA CTTACTCGGACGTCT GAGCAGCCCTACCAG CGGCCTTCTGGACAA TTACTCGGACGTCTG AGCAGCCCTACCAGG GGCCTTCTGGACAAG TACTCGGACGTCTGG GCAGCCCTACCAGGG GCCTTCTGGACAAGC ACTCGGACGTCTGGT CAGCCCTACCAGGGC CCTTCTGGACAAGCC CTCGGACGTCTGGTC AGCCCTACCAGGGCT CTTCTGGACAAGCCA TCGGACGTCTGGTCC GCCCTACCAGGGCTT TTCTGGACAAGCCAG CGGACGTCTGGTCCT CCCTACCAGGGCTTG TCTGGACAAGCCAGA GGACGTCTGGTCCTT CCTACCAGGGCTTGT CTGGACAAGCCAGAC GACGTCTGGTCCTTC CTACCAGGGCTTGTC TGGACAAGCCAGACA ACGTCTGGTCCTTCG TACCAGGGCTTGTCC GGACAAGCCAGACAA CGTCTGGTCCTTCGG ACCAGGGCTTGTCCA GACAAGCCAGACAAC GTCTGGTCCTTCGGG CCAGGGCTTGTCCAA ACAAGCCAGACAACT TCTGGTCCTTCGCGG CAGGGCTTGTCCAAC CAAGCCAGACAACTG CTGGTCCTTCGGGGT AGGGCTTGTCCAACG AAGCCAGACAACTGT TGGTCCTTCGGGGTC GGGCTTGTCCAACGA AGCCAGACAACTGTC GGTCCTTCGGGGTCG GGCTTGTCCAACGAG GCCAGACAACTGTCC GTCCTTCGGGGTCGT GCTTGTCCAACGAGC CCAGACAACTGTCCT TCCTTCGGGGTCGTC CTTGTCCAACGAGCA CAGACAACTGTCCTG CCTTCGGGGTCGTCC TTGTCCAACGAGCAA ACACAACTGTCCTGA CTTCGGGGTCGTCCT TGTCCAACGAGCAAG GACAACTGTCCTGAC TTCGGGGTCGTCCTC GTCCAACGAGCAAGT ACAACTGTCCTGACA TCGGGGTCGTCCTCT TCCAACGAGCAAGTC CAACTGTCCTGACAT CGGGGTCGTCCTCTG CCAACGAGCAAGTCC AACTGTCCTGACATG GGGGTCGTCCTCTGG CAACGAGCAAGTCCT ACTGTCCTGACATGC GGGTCGTCCTCTGGG AACGAGCAAGTCCTT CTGTCCTGACATGCT GGTCGTCCTCTGGGA ACGAGCAAGTCCTTC TGTCCTGACATGCTG GTCGTCCTCTGGGAG CGAGCAAGTCCTTCG GTCCTGACATGCTGT TCGTCCTCTGGGAGA GAGCAAGTCCTTCGC TCCTGACATGCTGTT CGTCCTCTGGGAGAT AGCAAGTCCTTCGCT CCTGACATGCTGTTT GTCCTCTGGGAGATC GCAAGTCCTTCGCTT CTGACATGCTGTTTG TCCTCTGGGAGATCG CAAGTCCTTCGCTTC TGACATGCTGTTTGA CCTCTGGGAGATCGC AAGTCCTTCGCTTCG GACATGCTGTTTGAA CTCTGGGAGATCGCC AGTCCTTCGCTTCGT ACATGCTGTTTGAAC TCTGGGAGATCGCCA GTCCTTCGCTTCGTC CATGCTGTTTGAACT CTGGGAGATCGCCAC TCCTTCGCTTCGTCA ATGCTGTTTGAACTG TGGGAGATCGCCACA CCTTCGCTTCGTCAT TGCTGTTTGAACTGA GGGAGATCGCCACAC CTTCGCTTCGTCATG GCTGTTTGAACTGAT GGAGATCGCCACACT TTCGCTTCGTCATGG CTGTTTGAACTGATG GAGATCGCCACACTG TCGCTTCGTCATGGA TGTTTGAACTGATGC AGATCGCCACACTGG CGCTTCGTCATGGAG GTTTGAACTGATGCG GATCGCCACACTGGC GCTTCGTCATGGAGG TTTGAACTGATGCGC ATCGCCACACTGGCC CTTCGTCATGGAGGG TTGAACTGATGCGCA TCGCCACACTGGCCG TTCGTCATGGAGGGC TGAACTGATGCGCAT CGCCACACTGGCCGA TCGTCATGGAGGGCG GAACTGATGCGCATG GCCACACTGGCCGAG CGTCATGGAGGGCGG AACTGATGCGCATGT CCACACTGGCCGAGC GTCATGGAGGGCGGC ACTGATGCGCATGTG CACACTGGCCGAGCA TCATGGAGGGCGGCC CTGATGCGCATGTGC ACACTGGCCGAGCAG CATGGAGGGCGGCCT TGATGCGCATGTGCT CACTGGCCGAGCAGC ATGGAGGGCGGCCTT GATGCGCATGTGCTG ATGCGCATGTGCTGG CAGCAGCATCAAAGA GCGAGGAGAACAAGC TGCGCATGTGCTGGC AGCAGCATCAAAGAG CGAGGAGAACAAGCT GCGCATGTGCTGGCA GCAGCATCAAAGAGG GAGGAGAACAAGCTG CGCATGTGCTGGCAG CAGCATCAAAGAGGA AGGAGAACAAGCTGC GCATGTGCTGGCAGT AGCATCAAAGAGGAG GGAGAACAAGCTGCC CATGTGCTGGCAGTA GCATCAAAGAGGAGA GAGAACAAGCTGCCC ATGTGCTGGCAGTAT CATCAAAGAGGAGAT AGAACAAGCTGCCCG TGTGCTGGCAGTATA ATCAAAGAGGAGATG GAACAAGCTGCCCGA GTGCTGGCAGTATAA TCAAAGAGGAGATGG AACAAGCTGCCCGAG TGCTGGCAGTATAAC CAAAGAGGAGATGGA ACAAGCTGCCCGAGC GCTGGCAGTATAACC AAAGAGGAGATGGAG CAAGCTGCCCGAGCC CTGGCAGTATAACCC AAGAGGAGATGGAGC AAGCTGCCCGAGCCG TGGCAGTATAACCCC AGAGGAGATGGAGCC AGCTGCCCGAGCCGG GGCAGTATAACCCCA GAGGAGATGGAGCCT GCTGCCCGAGCCGGA GCAGTATAACCCCAA AGGAGATGGAGCCTG CTGCCCGAGCCGGAG CAGTATAACCCCAAG GGAGATGGAGCCTGG TGCCCGAGCCGGAGG AGTATAACCCCAAGA GAGATGGAGCCTGGC GCCCGAGCCGGAGGA GTATAACCCCAAGAT AGATGGAGCCTGGCT CCCGAGCCGGAGGAG TATAACCCCAAGATG GATGGAGCCTGGCTT CCGAGCCGGAGGAGC ATAACCCCAAGATGA ATGGAGCCTGGCTTC CGAGCCGGAGGAGCT TAACCCCAAGATGAG TGGAGCCTGGCTTCC GAGCCGGAGGAGCTG AACCCCAAGATGAGG GGAGCCTGGCTTCCG AGCCGGAGGAGCTGG ACCCCAAGATGAGGC GAGCCTGGCTTCCGG GCCGGAGGAGCTGGA CCCCAAGATGAGGCC AGCCTGGCTTCCGGG CCGGAGGAGCTGGAC CCCAAGATGAGGCCT GCCTGGCTTCCGGGA CGGAGGAGCTGGACC CCAAGATGAGGCCTT CCTGGCTTCCGGGAG GGAGGAGCTGGACCT CAAGATGAGGCCTTC CTGGCTTCCGGGAGG GAGGAGCTGGACCTG AAGATGAGGCCTTCC TGGCTTCCGGGAGGT AGGAGCTGGACCTGG AGATGAGGCCTTCCT GGCTTCCGGGAGGTC GGAGCTGGACCTGGA GATGAGGCCTTCCTT GCTTCCGGGAGGTCT GAGCTGGACCTGGAG ATGAGGCCTTCCTTC CTTCCGGGAGGTCTC AGCTGGACCTGGAGC TGAGGCCTTCCTTCC TTCCGGGAGGTCTCC GCTGGACCTGGAGCC GAGGCCTTCCTTCCT TCCGGGAGGTCTCCT CTGGACCTGGAGCCA AGGCCTTCCTTCCTG CCGGGAGGTCTCCTT TGGACCTGGAGCCAG GGCCTTCCTTCCTGG CGGGAGGTCTCCTTC GGACCTGGAGCCAGA GCCTTCCTTCCTGGA GGGAGGTCTCCTTCT GACCTGGAGCCAGAG CCTTCCTTCCTGGAG GGAGGTCTCCTTCTA ACCTGGAGCCAGAGA CTTCCTTCCTGGAGA GAGGTCTCCTTCTAC CCTGGAGCCAGAGAA TTCCTTCCTGGAGAT AGGTCTCCTTCTACT CTGGAGCCAGAGAAC TCCTTCCTGGAGATC GGTCTCCTTCTACTA TGGAGCCAGAGAACA CCTTCCTGGAGATCA GTCTCCTTCTACTAC GGAGCCAGAGAACAT CTTCCTGGAGATCAT TCTCCTTCTACTACA GAGCCAGAGAACATG TTCCTGGAGATCATC CTCCTTCTACTACAG AGCCAGAGAACATGG TCCTGGAGATCATCA TCCTTCTACTACAGC GCCAGAGAACATGGA CCTGGAGATCATCAG CCTTCTACTACAGCG CCAGAGAACATGGAG CTGGAGATCATCAGC CTTCTACTACAGCGA CAGAGAACATGGAGA TGGAGATCATCAGCA TTCTACTACAGCGAG AGAGAACATGGAGAG GGAGATCATCAGCAG TCTACTACAGCGAGG GAGAACATGGAGAGC GAGATCATCAGCAGC CTACTACAGCGAGGA AGAACATGGAGAGCG AGATCATCAGCAGCA TACTACAGCGAGGAG GAACATGGAGAGCGT GATCATCAGCAGCAT ACTACAGCGAGGAGA AACATGGAGAGCGTC ATCATCAGCAGCATC CTACAGCGAGGAGAA ACATGGAGAGCGTCC TCATCAGCAGCATCA TACAGCGAGGAGAAC CATGGAGAGCGTCCC CATCAGCAGCATCAA ACAGCGAGGAGAACA ATGGAGAGCGTCCCC ATCAGCAGCATCAAA CAGCGAGGAGAACAA TGGAGAGCGTCCCCC TCAGCAGCATCAAAG AGCGAGGAGAACAAG GGAGAGCGTCCCCCT GAGAGCGTCCCCCTG ACACTCAGGACACAA CCAGCTTCGACGAGA AGAGCGTCCCCCTGG CACTCAGGACACAAG CAGCTTCGACGAGAG GAGCGTCCCCCTGGA ACTCAGGACACAAGG AGCTTCGACGAGAGA AGCGTCCCCCTGGAC CTCAGGACACAAGGC GCTTCGACGAGAGAC GCGTCCCCCTGGACC TCAGGACACAAGGCC CTTCGACGAGAGACA CGTCCCCCTGGACCC CAGGACACAAGGCCG TTCGACGAGAGACAG GTCCCCCTGGACCCC AGGACACAAGGCCGA TCGACGAGAGACAGC TCCCCCTGGACCCCT GGACACAAGGCCGAG CGACGAGAGACAGCC CCCCCTGGACCCCTC GACACAAGGCCGAGA GACGAGAGACAGCCT CCCCTGGACCCCTCG ACACAAGGCCGAGAA ACGAGAGACAGCCTT CCCTGGACCCCTCGG CACAAGGCCGAGAAC CGAGAGACAGCCTTA CCTGGACCCCTCGGC ACAAGGCCGAGAACG GAGAGACAGCCTTAC CTGGACCCCTCGGCC CAAGGCCGAGAACGG AGAGACAGCCTTACG TGGACCCCTCGGCCT AAGGCCGAGAACGGC GAGACAGCCTTACGC GGACCCCTCGGCCTC AGGCCGAGAACGGCC AGACAGCCTTACGCC GACCCCTCGGCCTCC GGCCGAGAACGGCCC GACAGCCTTACGCCC ACCCCTCGGCCTCCT GCCGAGAACGGCCCC ACAGCCTTACGCCCA CCCCTCGGCCTCCTC CCGAGAACGGCCCCG CAGCCTTACGCCCAC CCCTCGGCCTCCTCG CGAGAACGGCCCCGG AGCCTTACGCCCACA CCTCGGCCTCCTCGT GAGAACGGCCCCGGC GCCTTACGCCCACAT CTCGGCCTCCTCGTC AGAACGGCCCCGGCC CCTTACGCCCACATG TCGGCCTCCTCGTCC GAACGGCCCCGGCCC CTTACGCCCACATGA CGGCCTCCTCGTCCT AACGGCCCCGGCCCT TTACGCCCACATGAA GGCCTCCTCGTCCTC ACGGCCCCGGCCCTG TACGCCCACATGAAC GCCTCCTCGTCCTCC CGGCCCCGGCCCTGG ACGCCCACATGAACG CCTCCTCGTCCTCCC GGCCCCGGCCCTGGG CGCCCACATGAACGG CTCCTCGTCCTCCCT GCCCCGGCCCTGGGG GCCCACATGAACGGG TCCTCGTCCTCCCTG CCCCGGCCCTGGGGT CCCACATGAACGGGG CCTCGTCCTCCCTGC CCCGGCCCTGGGGTG CCACATGAACGGGGG CTCGTCCTCCCTGCC CCGGCCCTGGGGTGC CACATGAACGGGGGC TCGTCCTCCCTGCCA CGGCCCTGGGGTGCT ACATGAACGGGGGCC CGTCCTCCCTGCCAC GGCCCTGGGGTGCTG CATGAACGGGGGCCG GTCCTCCCTGCCACT GCCCTGGGGTGCTGG ATGAACGGGGGCCGC TCCTCCCTGCCACTG CCCTGGGGTGCTGGT TGAACGGGGGCCGCA CCTCCCTGCCACTGC CCTGGGGTGCTGGTC GAACGGGGGCCGCAA CTCCCTGCCACTGCC CTGGGGTGCTGGTCC AACGGGGGCCGCAAG TCCCTGCCACTGCCC TGGGGTGCTGGTCCT ACGGGGGCCGCAAGA CCCTGCCACTGCCCG GGGGTGCTGGTCCTC CGGGGGCCGCAAGAA CCTGCCACTGCCCGA GGGTGCTGGTCCTCC GGGGGCCGCAAGAAC CTGCCACTGCCCGAC GGTGCTGGTCCTCCG GGGGCCGCAAGAACG TGCCACTGCCCGACA GTGCTGGTCCTCCGC GGGCCGCAAGAACGA GCCACTGCCCGACAG TGCTGGTCCTCCGCG GGCCGCAAGAACGAG CCACTGCCCGACAGA GCTGGTCCTCCGCGC GCCGCAAGAACGAGC CACTGCCCGACAGAC CTGGTCCTCCGCGCC CCGCAAGAACGAGCG ACTGCCCGACAGACA TGGTCCTCCGCGCCA CGCAAGAACGAGCGG CTGCCCGACAGACAC GGTCCTCCGCGCCAG GCAAGAACGAGCGGG TGCCCGACAGACACT GTCCTCCGCGCCAGC CAAGAACGAGCGGGC GCCCGACAGACACTC TCCTCCGCGCCAGCT AAGAACGAGCGGGCC CCCGACAGACACTCA CCTCCGCGCCAGCTT AGAACGAGCGGGCCT CCGACAGACACTCAG CTCCGCGCCAGCTTC GAACGAGCGGGCCTT CGACAGACACTCAGG TCCGCGCCAGCTTCG AACGAGCGGGCCTTG GACAGACACTCAGGA CCGCGCCAGCTTCGA ACGAGCGGGCCTTGC ACAGACACTCAGGAC CGCGCCAGCTTCGAC CGAGCGGGCCTTGCC CAGACACTCAGGACA GCGCCAGCTTCGACG GAGCGGGCCTTGCCG AGACACTCAGGACAC CGCCAGCTTCGACGA AGCGGGCCTTGCCGC GACACTCAGGACACA GCCAGCTTCGACGAG GCGGCCCTTGCCGCT CGGGCCTTGCCGCTG GCAAACAGTAACGTG CAATCCATTCACAAG GGGCCTTGCCGCTGC CAAACAGTAACGTGT AATCCATTCACAAGC GGCCTTGCCGCTGCC AAACAGTAACGTGTG ATCCATTCACAAGCC GCCTTGCCGCTGCCC AACAGTAACGTGTGC TCCATTCACAAGCCT CCTTGCCGCTGCCCC ACAGTAACGTGTGCG CCATTCACAAGCCTC CTTGCCGCTGCCCCA CAGTAACGTGTGCGC CATTCACAAGCCTCC TTGCCGCTGCCCCAG AGTAACGTGTGCGCA ATTCACAAGCCTCCT TGCCGCTGCCCCAGT GTAACGTGTGCGCAC TTCACAAGCCTCCTG GCCGCTGCCCCAGTC TAACGTGTGCGCACG TCACAAGCCTCCTGT CCGCTGCCCCAGTCT AACGTGTGCGCACGC CACAAGCCTCCTGTA CGCTGCCCCAGTCTT ACGTGTGCGCACGCG ACAAGCCTCCTGTAC GCTGCCCCAGTCTTC CGTGTGCGCACGCGC CAAGCCTCCTGTACC CTGCCCCAGTCTTCG GTGTGCGCACGCGCA AAGCCTCCTGTACCT TGCCCCAGTCTTCGA TGTGCGCACGCGCAG AGCCTCCTGTACCTC GCCCCAGTCTTCGAC GTGCGCACGCGCAGC GCCTCCTGTACCTCA CCCCAGTCTTCGACC TGCGCACGCGCAGCG CCTCCTGTACCTCAG CCCAGTCTTCGACCT GCGCACGCGCAGCGG CTCCTGTACCTCAGT CCAGTCTTCGACCTG CGCACGCGCAGCGGG TCCTGTACCTCAGTG CAGTCTTCGACCTGC GCACGCGCAGCGGGG CCTGTACCTCAGTGG AGTCTTCGACCTGCT CACGCGCAGCGGGGT CTGTACCTCAGTGGA GTCTTCGACCTGCTG ACGCGCAGCGGGGTG TGTACCTCAGTGGAT TCTTCGACCTGCTGA CGCGCAGCGGGGTGG GTACCTCAGTGGATC CTTCGACCTGCTGAT GCGCAGCGGGGTGGG TACCTCAGTGGATCT TTCGACCTGCTGATC CGCAGCGGGGTGGGG ACCTCAGTGGATCTT TCGACCTGCTGATCC GCAGCGGGGTGGGGG CCTCAGTGGATCTTC CGACCTGCTGATCCT CAGCGGGGTGGGGGG CTCAGTGGATCTTCA GACCTGCTGATCCTT AGCGGGGTGGGGGGG TCAGTGGATCTTCAG ACCTGCTGATCCTTG GCGGGGTGGGGGGGG CAGTGGATCTTCAGT CCTGCTGATCCTTGG CGGGGTGGGGGGGGA AGTGGATCTTCAGTT CTGCTGATCCTTGGA GGGGTGGGGGGGGAG GTGGATCTTCAGTTC TGCTGATCCTTGGAT GGGTGGGGGGGGAGA TGGATCTTCAGTTCT GCTGATCCTTGGATC GGTGGGGGGGGAGAG GGATCTTCAGTTCTG CTGATCCTTGGATCC GTGGGGGGGGAGAGA GATCTTCAGTTCTGC TGATCCTTGGATCCT TGGGGGGGGAGAGAG ATCTTCAGTTCTGCC GATCCTTGGATCCTG GGGGGGGGAGAGAGA TCTTCAGTTCTGCCC ATCCTTGGATCCTGA GGGGGGGAGAGAGAG CTTCAGTTCTGCCCT TCCTTGGATCCTGAA GGGGGGAGAGAGAGT TTCAGTTCTGCCCTT CCTTGGATCCTGAAT GGGGGAGAGAGAGTT TCAGTTCTGCCCTTG CTTGGATCCTGAATC GGGGAGAGAGAGTTT CAGTTCTGCCCTTGC TTGGATCCTGAATCT GGGAGAGAGAGTTTT AGTTCTGCCCTTGCT TGGATCCTGAATCTG GGAGAGAGAGTTTTA GTTCTGCCCTTGCTG GGATCCTGAATCTGT GAGAGAGAGTTTTAA TTCTGCCCTTGCTGC GATCCTGAATCTGTG AGAGAGAGTTTTAAC TCTGCCCTTGCTGCC ATCCTGAATCTGTGC GAGAGAGTTTTAACA CTGCCCTTGCTGCCC TCCTGAATCTGTGCA AGAGAGTTTTAACAA TGCCCTTGCTGCCCG CCTGAATCTGTGCAA GAGAGTTTTAACAAT GCCCTTGCTGCCCGC CTGAATCTGTGCAAA AGAGTTTTAACAATC CCCTTGCTGCCCGCG TGAATCTGTGCAAAC GAGTTTTAACAATCC CCTTGCTGCCCGCGG GAATCTGTGCAAACA AGTTTTAACAATCCA CTTGCTGCCCGCGGG AATCTGTGCAAACAG GTTTTAACAATCCAT TTGCTGCCCGCGGGA ATCTGTGCAAACAGT TTTTAACAATCCATT TGCTGCCCGCGGGAG TCTGTGCAAACAGTA TTTAACAATCCATTC GCTGCCCGCGGGAGA CTGTGCAAACAGTAA TTAACAATCCATTCA CTGCCCGCGGGAGAC TGTGCAAACAGTAAC TAACAATCCATTCAC TGCCCGCGGGAGACA GTGCAAACAGTAACG AACAATCCATTCACA GCCCGCGGGAGACAG TGCAAACAGTAACGT ACAATCCATTCACAA CCCGCGGGAGACAGC CCGCGGGAGACAGCT ATGCAAGCAGCTTTT ACCTTAATGACAACA CGCGGGAGACAGCTT TGCAAGCAGCTTTTT CCTTAATGACAACAC GCGGGAGACAGCTTC GCAAGCAGCTTTTTA CTTAATGACAACACT CGGGAGACAGCTTCT CAAGCAGCTTTTTAT TTAATGACAACACTT GGGAGACAGCTTCTC AAGCAGCTTTTTATT TAATGACAACACTTA GGAGACAGCTTCTCT AGCAGCTTTTTATTC AATGACAACACTTAA GAGACAGCTTCTCTG GCAGCTTTTTATTCC ATGACAACACTTAAT AGACAGCTTCTCTGC CAGCTTTTTATTCCC TGACAACACTTAATA GACAGCTTCTCTGCA AGCTTTTTATTCCCT GACAACACTTAATAG ACAGCTTCTCTGCAG GCTTTTTATTCCCTG ACAACACTTAATAGC CAGCTTCTCTGCAGT CTTTTTATTCCCTGC CAACACTTAATAGCA AGCTTCTCTGCAGTA TTTTTATTCCCTGCC AACACTTAATAGCAA GCTTCTCTGCAGTAA TTTTATTCCCTGCCC ACACTTAATAGCAAC CTTCTCTGCAGTAAA TTTATTCCCTGCCCA CACTTAATAGCAACA TTCTCTGCAGTAAAA TTATTCCCTGCCCAA ACTTAATAGCAACAG TCTCTGCAGTAAAAC TATTCCCTGCCCAAA CTTAATAGCAACAGA CTCTGCAGTAAAACA ATTCCCTGCCCAAAC TTAATAGCAACAGAG TCTGCAGTAAAACAC TTCCCTGCCCAAACC TAATAGCAACAGAGC CTGCAGTAAAACACA TCCCTGCCCAAACCC AATAGCAACAGAGCA TGCAGTAAAACACAT CCCTGCCCAAACCCT ATAGCAACAGAGCAC GCAGTAAAACACATT CCTGCCCAAACCCTT TAGCAACAGAGCACT CAGTAAAACACATTT CTGCCCAAACCCTTA AGCAACAGAGCACTT AGTAAAACACATTTG TGCCCAAACCCTTAA GCAACAGAGCACTTG GTAAAACACATTTGG GCCCAAACCCTTAAC CAACAGAGCACTTGA TAAAACACATTTGGG CCCAAACCCTTAACT AACAGAGCACTTGAG AAAACACATTTGGGA CCAAACCCTTAACTG ACAGAGCACTTGAGA AAACACATTTGGGAT CAAACCCTTAACTGA CAGAGCACTTGAGAA AACACATTTGGGATG AAACCCTTAACTGAC AGAGCACTTGAGAAC ACACATTTGGGATGT AACCCTTAACTGACA GAGCACTTGAGAACC CACATTTGGGATGTT ACCCTTAACTGACAT AGCACTTGAGAACCA ACATTTGGGATGTTC CCCTTAACTGACATG GCACTTGAGAACCAG CATTTGGGATGTTCC CCTTAACTGACATGG CACTTGAGAACCAGT ATTTGGGATGTTCCT CTTAACTGACATGGG ACTTGAGAACCAGTC TTTGGGATGTTCCTT TTAACTGACATGGGC CTTGAGAACCAGTCT TTGGGATGTTCCTTT TAACTGACATGGGCC TTGAGAACCAGTCTC TGGGATGTTCCTTTT AACTGACATGGGCCT TGAGAACCAGTCTCC GGGATGTTCCTTTTT ACTGACATGGGCCTT GAGAACCAGTCTCCT GGATGTTCCTTTTTT CTGACATGGGCCTTT AGAACCAGTCTCCTC GATGTTCCTTTTTTC TGACATGGGCCTTTA GAACCAGTCTCCTCA ATGTTCCTTTTTTCA GACATGGGCCTTTAA AACCAGTCTCCTCAC TGTTCCTTTTTTCAA ACATGGGCCTTTAAG ACCAGTCTCCTCACT GTTCCTTTTTTCAAT CATGGGCCTTTAAGA CCAGTCTCCTCACTC TTCCTTTTTTCAATA ATGGGCCTTTAAGAA CAGTCTCCTCACTCT TCCTTTTTTCAATAT TGGGCCTTTAAGAAC AGTCTCCTCACTCTG CCTTTTTTCAATATG GGGCCTTTAAGAACC GTCTCCTCACTCTGT CTTTTTTCAATATGC GGCCTTTAAGAACCT TCTCCTCACTCTGTC TTTTTTCAATATGCA GCCTTTAAGAACCTT CTCCTCACTCTGTCC TTTTTCAATATGCAA CCTTTAAGAACCTTA TCCTCACTCTGTCCC TTTTCAATATGCAAG CTTTAAGAACCTTAA CCTCACTCTGTCCCT TTTCAATATGCAAGC TTTAAGAACCTTAAT CTCACTCTGTCCCTG TTCAATATGCAAGCA TTAAGAACCTTAATG TCACTCTGTCCCTGT TCAATATGCAAGCAG TAAGAACCTTAATGA CACTCTGTCCCTGTC CAATATGCAAGCAGC AAGAACCTTAATGAC ACTCTGTCCCTGTCC AATATGCAAGCAGCT AGAACCTTAATGACA CTCTGTCCCTGTCCT ATATGCAAGCAGCTT GAACCTTAATGACAA TCTGTCCCTGTCCTT TATGCAAGCAGCTTT AACCTTAATGACAAC CTGTCCCTGTCCTTC TGTCCCTGTCCTTCC AATAATTGCCACAAG GTCCCTGTGGCCCCA GTCCCTGTCCTTCCC ATAATTGCCACAAGT TCCCTGTGGCCCCAT TCCCTGTCCTTCCCT TAATTGCCACAAGTC CCCTGTGGCCCCATC CCCTGTCCTTCCCTG AATTGCCACAAGTCC CCTGTGGCCCCATCC CCTGTCCTTCCCTGT ATTGCCACAAGTCCA CTGTGGCCCCATCCA CTGTCCTTCCCTGTT TTGCCACAAGTCCAG TGTGGCCCCATCCAA TGTCCTTCCCTGTTC TGCCACAAGTCCAGC GTGGCCCCATCCAAC GTCCTTCCCTGTTCT GCCACAAGTCCAGCT TGGCCCCATCCAACC TCCTTCCCTGTTCTC CCACAAGTCCAGCTG GGCCCCATCCAACCA CCTTCCCTGTTCTCC CACAAGTCCAGCTGG GCCCCATCCAACCAC CTTCCCTGTTCTCCC ACAAGTCCAGCTGGG CCCCATCCAACCACT TTCCCTGTTCTCCCT CAAGTCCAGCTGGGA CCCATCCAACCACTG TCCCTGTTCTCCCTT AAGTCCAGCTGGGAA CCATCCAACCACTGT CCCTGTTCTCCCTTT AGTCCAGCTGGGAAG CATCCAACCACTGTA CCTGTTCTCCCTTTC GTCCAGCTGGGAAGC ATCCAACCACTGTAC CTGTTCTCCCTTTCT TCCAGCTGGGAAGCC TCCAACCACTGTACA TGTTCTCCCTTTCTC CCAGCTGGGAAGCCC CCAACCACTGTACAC GTTCTCCCTTTCTCT CAGCTGGGAAGCCCT CAACCACTGTACACA TTCTCCCTTTCTCTC AGCTGGGAAGCCCTT AACCACTGTACACAC TCTCCCTTTCTCTCT GCTGGGAAGCCCTTT ACCACTGTACACACC CTCCCTTTCTCTCTC CTGGGAAGCCCTTTT CCACTGTACACACCC TCCCTTTCTCTCTCC TGGGAAGCCCTTTTT CACTGTACACACCCG CCCTTTCTCTCTCCT GGGAAGCCCTTTTTA ACTGTACACACCCGC CCTTTCTCTCTCCTC GGAAGCCCTTTTTAT CTGTACACACCCGCC CTTTCTCTCTCCTCT GAAGCCCTTTTTATC TGTACACACCCGCCT TTTCTCTCTCCTCTC AAGCCCTTTTTATCA GTACACACCCGCCTG TTCTCTCTCCTCTCT AGCCCTTTTTATCAG TACACACCCGCCTGA TCTCTCTCCTCTCTG GCCCTTTTTATCAGT ACACACCCGCCTGAC CTCTCTCCTCTCTGC CCCTTTTTATCAGTT CACACCCGCCTGACA TCTCTCCTCTCTGCT CCTTTTTATCAGTTT ACACCCGCCTGACAC CTCTCCTCTCTGCTT CTTTTTATCAGTTTG CACCCGCCTGACACC TCTCCTCTCTGCTTC TTTTTATCAGTTTGA ACCCGCCTGACACCG CTCCTCTCTGCTTCA TTTTATCAGTTTGAG CCCGCCTGACACCGT TCCTCTCTGCTTCAT TTTATCAGTTTGAGG CCGCCTGACACCGTG CCTCTCTGCTTCATA TTATCAGTTTGAGGA CGCCTGACACCGTGG CTCTCTGCTTCATAA TATCAGTTTGAGGAA GCCTGACACCGTGGG TCTCTGCTTCATAAC ATCAGTTTGAGGAAG CCTGACACCGTGGGT CTCTGCTTCATAACG TCAGTTTGAGGAAGT CTGACACCGTGGGTC TCTGCTTCATAACGG CAGTTTGAGGAAGTG TGACACCGTGGGTCA CTGCTTCATAACGGA AGTTTGAGGAAGTGG GACACCGTGGGTCAT TGCTTCATAACGGAA GTTTGAGGAAGTGGC ACACCGTGGGTCATT GCTTCATAACGGAAA TTTGAGGAAGTGGCT CACCGTGGGTCATTA CTTCATAACGGAAAA TTGAGGAAGTGGCTG ACCGTGGGTCATTAC TTCATAACGGAAAAA TGAGGAAGTGGCTGT CCGTGGGTCATTACA TCATAACGGAAAAAT GAGGAAGTGGCTGTC CGTGGGTCATTACAA CATAACGGAAAAATA AGGAAGTGGCTGTCC GTGGGTCATTACAAA ATAACGGAAAAATAA GGAAGTGGCTGTCCC TGGGTCATTACAAAA TAACGGAAAAATAAT GAAGTGGCTGTCCCT GGGTCATTACAAAAA AACGGAAAAATAATT AAGTGGCTGTCCCTG GGTCATTACAAAAAA ACGGAAAAATAATTG AGTGGCTGTCCCTGT GTCATTACAAAAAAA CGGAAAAATAATTGC GTGGCTGTCCCTGTG TCATTACAAAAAAAC GGAAAAATAATTGCC TGGCTGTCCCTGTGG CATTACAAAAAAACA GAAAAATAATTGCCA GGCTGTCCCTGTGGC ATTACAAAAAAACAC AAAAATAATTGCCAC GCTGTCCCTGTGGCC TTACAAAAAAACACG AAAATAATTGCCACA CTGTCCCTGTGGCCC TACAAAAAAACACGT AAATAATTGCCACAA TGTCCCTGTGGCCCC ACAAAAAAACACGTG CAAAAAAACACGTGG ATGAAATTTACAAAG TAATTTTGCCAAAAT AAAAAAACACGTGGA TGAAATTTACAAAGG AATTTTGCCAAAATC AAAAAACACGTGGAG GAAATTTACAAAGGG ATTTTGCCAAAATCC AAAAACACGTGGAGA AAATTTACAAAGGGC TTTTGCCAAAATCCT AAAACACGTGGAGAT AATTTACAAAGGGCC TTTGCCAAAATCCTG AAACACGTGGAGATG ATTTACAAAGGGCCA TTGCCAAAATCCTGA AACACGTGGAGATGG TTTACAAAGGGCCAT TGCCAAAATCCTGAA ACACGTGGAGATGGA TTACAAAGGGCCATC GCCAAAATCCTGAAC CACGTGGAGATGGAA TACAAAGGGCCATCG CCAAAATCCTGAACT ACGTGGAGATGGAAA ACAAAGGGCCATCGT CAAAATCCTGAACTT CGTGGAGATGGAAAT CAAAGGGCCATCGTT AAAATCCTGAACTTT GTGGAGATGGAAATT AAAGGGCCATCGTTC AAATCCTGAACTTTC TGGAGATGGAAATTT AAGGGCCATCGTTCA AATCCTGAACTTTCT GGAGATGGAAATTTT AGGGCCATCGTTCAT ATCCTGAACTTTCTC GAGATGGAAATTTTT GGGCCATCGTTCATC TCCTGAACTTTCTCC AGATGGAAATTTTTA GGCCATCGTTCATCC CCTGAACTTTCTCCC GATGGAAATTTTTAC GCCATCGTTCATCCA CTGAACTTTCTCCCT ATGGAAATTTTTACC CCATCGTTCATCCAA TGAACTTTCTCCCTC TGGAAATTTTTACCT CATCGTTCATCCAAG GAACTTTCTCCCTCA GGAAATTTTTACCTT ATCGTTCATCCAAGG AACTTTCTCCCTCAT GAAATTTTTACCTTT TCGTTCATCCAAGGC ACTTTCTCCCTCATC AAATTTTTACCTTTA CGTTCATCCAAGGCT CTTTCTCCCTCATCG AATTTTTACCTTTAT GTTCATCCAAGGCTG TTTCTCCCTCATCGG ATTTTTACCTTTATC TTCATCCAAGGCTGT TTCTCCCTCATCGGC TTTTTACCTTTATCT TCATCCAAGGCTGTT TCTCCCTCATCGGCC TTTTACCTTTATCTT CATCCAAGGCTGTTA CTCCCTCATCGGCCC TTTACCTTTATCTTT ATCCAAGGCTGTTAC TCCCTCATCGGCCCG TTACCTTTATCTTTC TCCAAGGCTGTTACC CCCTCATCGGCCCGG TACCTTTATCTTTCA CCAAGGCTGTTACCA CCTCATCGGCCCGGC ACCTTTATCTTTCAC CAAGGCTGTTACCAT CTCATCGGCCCGGCG CCTTTATCTTTCACC AAGGCTGTTACCATT TCATCGGCCCGGCGC CTTTATCTTTCACCT AGGCTGTTACCATTT CATCGGCCCGGCGCT TTTATCTTTCACCTT GGCTGTTACCATTTT ATCGGCCCGGCGCTG TTATCTTTCACCTTT GCTGTTACCATTTTA TCGGCCCGGCGCTGA TATCTTTCACCTTTC CTGTTACCATTTTAA CGGCCCGGCGCTGAT ATCTTTCACCTTTCT TGTTACCATTTTAAC GGCCCGGCGCTGATT TCTTTCACCTTTCTA GTTACCATTTTAACG GCCCGGCGCTGATTC CTTTCACCTTTCTAG TTACCATTTTAACGC CCCGGCGCTGATTCC TTTCACCTTTCTAGG TACCATTTTAACGCT CCGGCGCTGATTCCT TTCACCTTTCTAGGG ACCATTTTAACGCTG CGGCGCTGATTCCTC TCACCTTTCTAGGGA CCATTTTAACGCTGC GGCGCTGATTCCTCG CACCTTTCTAGGGAC CATTTTAACGCTGCC GCGCTGATTCCTCGT ACCTTTCTAGGGACA ATTTTAACGCTGCCT CGCTGATTCCTCGTG CCTTTCTAGGGACAT TTTTAACGCTGCCTA GCTGATTCCTCGTGT CTTTCTAGGGACATG TTTAACGCTGCCTAA CTGATTCCTCGTGTC TTTCTAGGGACATGA TTAACGCTGCCTAAT TGATTCCTCGTGTCC TTCTAGGGACATGAA TAACGCTGCCTAATT GATTCCTCGTGTCCG TCTAGGGACATGAAA AACGCTGCCTAATTT ATTCCTCGTGTCCGG CTAGGGACATGAAAT ACGCTGCCTAATTTT TTCCTCGTGTCCGGA TAGGGACATGAAATT CCCTGCCTAATTTTG TCCTCGTGTCCGGAG AGGGACATGAAATTT GCTGCCTAATTTTGC CCTCGTGTCCGGAGG GGGACATGAAATTTA CTGCCTAATTTTGCC CTCGTGTCCGGAGGC GGACATGAAATTTAC TGCCTAATTTTGCCA TCGTGTCCGGAGGCA GACATGAAATTTACA GCCTAATTTTGCCAA CGTGTCCGGAGGCAT ACATGAAATTTACAA CCTAATTTTGCCAAA GTGTCCGGAGGCATG CATGAAATTTACAAA CTAATTTTGCCAAAA TGTCCGGAGGCATGG GTCCGGAGGCATGGG CGACACACTCCGTCC CAGGTCTCATTGCTT TCCGGAGGCATGGGT GACACACTCCGTCCA AGGTCTCATTGCTTC CCGGAGGCATGGGTG ACACACTCCGTCCAT GGTCTCATTGCTTCT CGGAGGCATGGGTGA CACACTCCGTCCATC GTCTCATTGCTTCTG GGAGGCATGGGTGAG ACACTCCGTCCATCC TCTCATTGCTTCTGA GAGGCATGGGTGAGC CACTCCGTCCATCCG CTCATTGCTTCTGAC AGGCATGGGTGAGCA ACTCCGTCCATCCGA TCATTGCTTCTGACT GGCATGGGTGAGCAT CTCCGTCCATCCGAC CATTGCTTCTGACTA GCATGGGTGAGCATG TCCGTCCATCCGACT ATTGCTTCTGACTAG CATGGGTGAGCATGG CCGTCCATCCGACTG TTGCTTCTGACTAGA ATGGGTGAGCATGGC CGTCCATCCGACTGC TGCTTCTGACTAGAT TGGGTGAGCATGGCA GTCCATCCGACTGCC GCTTCTGACTAGATT GGGTGAGCATGGCAG TCCATCCGACTGCCC CTTCTGACTAGATTA GGTGAGCATGGCAGC CCATCCGACTGCCCC TTCTGACTAGATTAT GTGAGCATGGCAGCT CATCCGACTGCCCCT TCTGACTAGATTATT TGAGCATGGCAGCTG ATCCGACTGCCCCTG CTGACTAGATTATTA GAGCATGGCAGCTGG TCCGACTGCCCCTGC TGACTAGATTATTAT AGCATGGCAGCTGGT CCGACTGCCCCTGCT GACTAGATTATTATT GCATGGCAGCTGGTT CGACTGCCCCTGCTG ACTAGATTATTATTT CATGGCAGCTGGTTG GACTGCCCCTGCTGT CTAGATTATTATTTG ATGGCAGCTGGTTGC ACTGCCCCTGCTGTG TAGATTATTATTTGG TGGCAGCTGGTTGCT CTGCCCCTGCTGTGC AGATTATTATTTGGG GGCAGCTGGTTGCTC TGCCCCTGCTGTGCT GATTATTATTTGGGG GCAGCTGGTTGCTCC GCCCCTGCTGTGCTG ATTATTATTTGGGGG CAGCTGGTTGCTCCA CCCCTGCTGTGCTGC TTATTATTTGGGGGA AGCTGGTTGCTCCAT CCCTGCTGTGCTGCT TATTATTTGGGGGAA GCTGGTTGCTCCATT CCTGCTGTGCTGCTC ATTATTTGGGGGAAC CTGGTTGCTCCATTT CTGCTGTGCTGCTCA TTATTTGGGGGAACT TGGTTGCTCCATTTG TGCTGTGCTGCTCAA TATTTGGGGGAACTG GGTTGCTCCATTTGA GCTGTGCTGCTCAAG ATTTGGGGGAACTGG GTTGCTCCATTTGAG CTGTGCTGCTCAAGG TTTGGGGGAACTGGA TTGCTCCATTTGAGA TGTGCTGCTCAAGGC TTGGGGGAACTGGAC TGCTCCATTTGAGAG GTGCTGCTCAAGGCC TGGGGGAACTGGACA GCTCCATTTGAGAGA TGCTGCTCAAGGCCA GGGGGAACTGGACAC CTCCATTTGAGAGAC GCTGCTCAAGGCCAC GGGGAACTGGACACA TCCATTTGAGAGACA CTGCTCAAGGCCACA GGGAACTGGACACAA CCATTTGAGAGACAC TGCTCAAGGCCACAG GGAACTGGACACAAT CATTTGAGAGACACG GCTCAAGGCCACAGG GAACTGGACACAATA ATTTGAGAGACACGC CTCAAGGCCACAGGC AACTGGACACAATAG TTTGAGAGACACGCT TCAAGGCCACAGGCA ACTGGACACAATAGG TTGAGAGACACGCTG CAAGGCCACAGGCAC CTGGACACAATAGGT TGAGAGACACGCTGG AAGGCCACAGGCACA TGGACACAATAGGTC GAGAGACACGCTGGC AGGCCACAGGCACAC GGACACAATAGGTCT AGAGACACGCTGGCG GGCCACAGGCACACA GACACAATAGGTCTT GAGACACGCTGGCGA GCCACAGGCACACAG ACACAATAGGTCTTT AGACACGCTGGCGAC CCACAGGCACACAGG CACAATAGGTCTTTC GACACGCTGGCGACA CACAGGCACACAGGT ACAATAGGTCTTTCT ACACGCTGGCGACAC ACAGGCACACAGGTC CAATAGGTCTTTCTC CACGCTGGCGACACA CAGGCACACAGGTCT AATAGGTCTTTCTCT ACGCTGGCGACACAC AGGCACACAGGTCTC ATAGGTCTTTCTCTC CGCTGGCGACACACT GGCACACAGGTCTCA TAGGTCTTTCTCTCA GCTGGCGACACACTC GCACACAGGTCTCAT AGGTCTTTCTCTCAG CTGGCGACACACTCC CACACAGGTCTCATT GGTCTTTCTCTCAGT TGGCGACACACTCCG ACACAGGTCTCATTG GTCTTTCTCTCAGTG GGCGACACACTCCGT CACAGGTCTCATTGC TCTTTCTCTCAGTGA GCGACACACTCCGTC ACAGGTCTCATTGCT CTTTCTCTCAGTGAA TTTCTCTCAGTGAAG TTCTCTCAGTGAAGG TCTCTCAGTGAAGGT CTCTCAGTGAAGGTG TCTCAGTGAAGGTGG CTCAGTGAAGGTGGG TCAGTGAAGGTGGGG CAGTGAAGGTGGGGA AGTGAAGGTGGGGAG GTGAAGGTGGGGAGA TGAAGGTGGGGAGAA GAAGGTGGGGAGAAG AAGGTGGGGAGAAGC AGGTGGGGAGAAGCT GGTGGGGAGAAGCTG GTGGGGAGAAGCTGA TGGGGAGAAGCTGAA GGGGAGAAGCTGAAC GGGAGAAGCTGAACC GGAGAAGCTGAACCG GAGAAGCTGAACCGG AGAAGCTGAACCGGC
EXAMPLE 9 Inhibition of IGF-I Binding by Antisense Oligonucleotides to IGf-I Receptor[0059] Sub-confluent HaCaT cells were treated as described above with phosphorothioate oligonucleotides IGFR.AS (antisense: 5′-ATCTCTCCGCTTCCTTT-3′; [SEQ ID NO. 10]; ref 13) and IGFR.S (sense control: 5′-GAAAGGAAGCGGAGAGAT-3′; [SEQ ID NO. 11]; Ref 13) IGF-I binding to the cell monolayers was then measured as 125I-IGF-I.
EXAMPLE 10 Inhibition of IGFBP-3 Production Using Antisense Oligonucleotides[0060] The results of this experiment are shown in FIGS. 7 and 8.
[0061] HaCaT cells were initially plated in DMEM with 10% v/v serum, then AS oligo experiments were performed in complete “Keratinocyte-SFM” (Gibco) to exclude the influence of exogenous IGFBPs. Oligos were synthesised as phosphorothioate (nuclease-resistant) derivatives (Bresatec, South Australia) and were as follows: antisense: AS2, 5′-GCGCCCGCTGCATGACGCCTCAAC-3′ (IGFBP-3 start codon); control AS2NS, 5′-CGGAGATGCCGCATGCCAGCGCAGG-3′; AS4, 5′-AGGCGGCTGACGGCACTA-3′; AS4NS, 5′-GACAGCGTCGGAGCGATC-3′; IGFRAS, 5′-ATCTCTCCGCTTCCTTTC-3′; IGFRS, 5′-GAAAGGAAGCGGAGAGAT-3′. Oligos to IGFBP-3 were based on the published sequence of Spratt et al [12]. AS oligos were added to HaCaT monolayers in 0.5 ml medium in 24-well plates at the concentrations and addition frequencies indicated. IGFBP-3 measured in cell-conditioned medium using a dot-blot assay, adapted from the Western ligand blot method of Hossenlopp et al [11], in which 100 &mgr;l of conditioned medium was applied to nitrocellulose filters with a vacuum dot-blot apparatus. After drying the membranes at 37° C., relative amounts of IGFBP are determined by 125I-IGF-I-binding, autoradiography and computerised imaging densitometry. Triplicate wells (except in FIG. 7, where duplicate wells were measured as shown) were analysed and corrected for changes in cell number per well. Relative cell number per well was determined using an amido black dye method, developed specifically for cultured monolayers of HaCaT cells (14). Cell numbers differed by less than 10% after treatment. For oligos to the IGF receptor, receptor quantitation in intact HaCaT monolayers was by overnight incubation with 125I-IGF-I (30,000 cpm/well) at 4° C.
EXAMPLE11 Inhibition of IGFBP-2 Production Using Ribozymes[0062] Experiments involving ribozymes are generally conducted as described in Internaitonal Patent Application No. WO 89/05852 and in Haselhoff and Gerlach [8]. Ribozymes are constructed with a hybridising region which is complementary in nucleotide sequence to at least part of a target RNA which, in this case, encodes IGFBP-2. Activity of ribozymes is measurable on, for example, Northern blots or using animal models such as in the nude mouse model (15; 16) or the “flaky skin” mouse model (17; 18).
EXAMPLE 12 Inhibition of IGFBP-3 Production Using Ribozymes[0063] The methods described in Example 11 are used for the screening of ribozymes which inhibit IGFBP-3 production. The activity of the ribozymes is determined as in Example 11.
EXAMPLE 13 Inhibition of IGF-1 Production Using Ribozymes[0064] The methods described in Example 11 are used for the screening of ribozymes which inhibit IGF-1 production. The activity of the ribozymes is determined as in Example 11.
EXAMPLE 14 Inhibition of IGF-1 Receptor Production Using Ribozymes[0065] The methods described in Example 11 are used for the screening of ribozymes which inhibit IGF-1 production. The activity of the ribozymes is determined as in Example 11
[0066] Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. It is to be understood that the invention includes all such variations and modifications. The invention also includes all of the steps, features, compositions and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations of any two or more of said steps or features.
[0067] References:
[0068] 1. Sara V Physiological Reviews 70: 591-614, 1990.
[0069] 2. Rechler M M and Brown A L Growth Regulation 2: 55-68, 1992.
[0070] 3. Clemmons D R Growth Regn 2: 80, 1992.
[0071] 4. Oakes S R, K M Haynes, M J Waters, A C Herington and G A Werther J. Clin Endocrinol Metab 73: 1368-1373, 1992.
[0072] 5. Camacho-Hubner C et al. J Biol Chem 267: 11949-11956, 1992.
[0073] 6. Neely K E et al. J Inv Derm 96: 104, 1991.
[0074] 7. Ts'O POP; Aurelian L, Chang E and Miller P S. Nonionic oligonucleotide analogs (Matagen TM) as anticodic agents in duplex and triplex formation. in “Antisense Strategies”, Annals of the New York Academy of Sciences 660:159-177 (Baserga R and Denhardt D T, eds.), 1993.
[0075] 8. Haseloff J and Gerlach L Nature 334: 586-591, 1988.
[0076] 9. Boukamp P, Petrussevska R T, Breitkreuz D, Hornung J, Markham A, Fusenig N E. J Cell Biol 106: 761-771, 1988.
[0077] 10. Rheinwald and Green Cell 6: 331-344, 1975.
[0078] 11. Hossenlopp P, Seurin D, Segovia-Quinson B, Hardouin S, Binoux M. Anal Biochem 154: 138-143, 1986.
[0079] 12. Spratt S K, Tatsuno G P, Yamanaka M K, Ark B C, Detmer J, Mascarenhas D, Flynn J, Talkington-Verser C, Spencer E M. Growth Factors 3: 63-72, 1990.
[0080] 13. Pietrzkowski, Z, Sell C, Lammers R, Ullrich A and Baserga R. Mol. Cell. Biol. 12: 3883-3889, 1992.
[0081] 14. Schulz J, Dettlaff S, Fritzsche U, Harms U, Schiebel H, Derer W, Fusenig N E, Hulsen A and Bohm M. J. Immunol Meth. 167: 1-13, 1994.
[0082] 15. Baker B S, Brent L, Valdimarsson H, Powles A V, Al-Imara L, Walker M and Fry L. Brit. J Bermatol 126: 105-110, 1992.
[0083] 16. Nanney L B et al J Invest. Bermatol 98: 296-301, 1992.
[0084] 17. Sundberg J P et al Immunol. Investigations 22: 389401, 1993.
[0085] 18. Sundberg J P et al J Invest. Dermatol 102: 781-788, 1994.
Claims
1. A method for ameliorating the effects of a proliferative and/or inflammatory skin disorder in a mammal, said method comprising contacting the proliferating and/or inflamed skin or skin capable of proliferation and/or inflammation with an effective amount of a nucleic acid molecule or chemical analogue thereof capable of inhibiting or otherwise reducing growth factor mediated cell proliferation and/or inflammation.
2. A method according to claim 1 wherein cell proliferation and/or inflammation is mediated by at least one of insulin-like growth factor I (IGF-I ), keratinocyte growth factor (KGF), transforming growth factor-&agr; (TGF&agr;), tumour necrosis factor-&agr; (TNF&agr;), interleukin (IL)-1 (IL-1), IL-4, IL-6, IL-8 and/or basic fibroblast growth factor (bFGF).
3. A method according to claim 2 wherein cell proliferation and/or inflammation is mediated by IGF-I.
4. A method according to claim 1 wherein the nucleic acid molecule inhibits or otherwise reduces IGF-I mediated cell proliferation and/or inflammation.
5. A method according to claim 1 wherein the proliferative or inflammatory skin disorder is psoriasis, ichthyosis, pityriasis, rubra, pilaris, serborrhoea, keloids, keratosis, neoplasias, scleroderma, warts, benign growths or cancers of the skin.
6. A method according to claim 5 wherein the skin condition is psoriasis.
7. A method according to claim 1 or 4 or 6 wherein the mammal is a human.
8. A method according to claim 1 or 4 or 6 wherein the nucleic acid molecule is capable of inhibiting, reducing or otherwise interfering with IGF-I-interaction with its receptor.
9. A method according to claim 8 wherein the nucleic acid molecule is an antisense molecule capable of reducing expression of a gene encoding IGF-I, IGF-I-receptor or an IGF binding protein (IGFBP).
10. A method according to claim 9 wherein the nucleic acid molecule is an antisense molecule capable of reducing expression of a gene encoding IGFBP-2, -3, -4, -5 or -6.
11. A method according to claim 10 wherein the nucleic acid molecule is an antisense molecule capable of reducing expression of a gene encoding IGFBP-2 or IGFBP-3.
12. A method according to claim 11 wherein the antisense molecule is at least about 15 nucleotides in length and is capable of interacting with at least one sequence selected from the list set forth in Example 6 or Example 7.
13. A method according to claim 11 wherein the antisense molecule comprises the nucleotide sequence:
- 8 5′-ATCTCTCCGCTTCCTTTC-3′. [SEQ ID NO:10]
14. A nucleic acid molecule comprising at least about 10 nucleotides capable of hybridising to or forming a heteroduplex or otherwise interacting with an RNA molecule directed from a gene corresponding to a genomic form of SEQ ID NO: 1 and/or SEQ ID NO: 2 and which thereby reduces or inhibits translation of said RNA molecule.
15. A nucleic acid molecule according to claim 14 wherein said molecule comprises at least about 15 nucleotides.
16. A nucleic acid molecule according to claim 15 wherein said molecule is capable of interacting with at least one nucleotide sequence selected from the list set forth in Example 6 and Example 7.
17. A nucleic acid molecule according to claim 15 or 16 comprising the nucleotide sequence:
- 9 5′-ATCTCTCCGCTTCCTTTC-3′. [SEQ ID NO:10]
18. A method of ameliorating the effects of psoriasis, said method comprising contacting proliferating skin or skin capable of proliferation with an effective amount of one or more nucleic acid molecules or chemical analogues thereof capable of inhibiting or otherwise reducing IGF-I mediated cell proliferation wherein said one or more molecules comprises a polynucleotide capable of interacting with mRNA directed from an IGF-I gene, an IGF-I receptor gene or a gene encoding an IGFBP.
19. A method according to claim 18 wherein the IGFBP is IGFBP-2 or IGFBP-3.
20. A method according to claim 18 or 19 wherein the mammal is a human.
21. A method according to claim 20 wherein the nucleic acid molecule is capable of interacting with a nucleotide sequence selected from the list set forth in Example 6 or Example 7.
22. A method according to claim 18 wherein the nucleic acid molecule comprises the nucleotide sequence:
- 10 5′-ATCTCTCCGCTTCCTTTC-3′. [SEQ ID NO:10]
23. A pharmaceutical composition for topical administration said composition comprising a nucleic acid molecule capable of inhibiting or otherwise reducing IGF-I mediated cell proliferation said composition further comprising one or more pharmaceutically acceptable carriers and/or diluents.
24. A pharmaceutical composition according to claim 23 wherein the nucleic acid molecule is an antisense molecule to a gene encoding IGF-I, IGF-I-receptor or an IGFBP.
25. A pharmaceutical composition according to claim 24 wherein the nucleic acid molecule is capable of targeting a gene encoding IGFBP-2 and/or IGFBP-3.
26. A pharmaceutical composition according to claim 24 capable of interacting with at least one nucleotide sequence set forth in Example 6 or Example 7.
27. Use of a nucleic acid molecule in the manufacture of a medicament for the treatment of a proliferative and/or inflammatory skin disorder mediated by IGF-I.
28. Use according to claim 27 wherein the skin disorder is psoriasis.
29. A ribozyme comprising a hybridising region and a catalytic region wherein the hybridising region is capable of hybridising to at least part of a target mRNA sequence transcribed from a genomic gene corresponding to SEQ ID NO: 1or SEQ ID NO: 2 wherein said catalytic domain is capable of cleaving said target mRNA sequence to reduce or inhibit IGF-I mediated cell proliferation or inflammation.
Type: Application
Filed: Feb 23, 2001
Publication Date: May 22, 2003
Applicant: ROYAL CHILDREN'S HOSPITAL RESEARCH FOUNDATION
Inventors: George Arthur Werther (Camberwell), Christopher John Wraight (Blackburn)
Application Number: 09791196
International Classification: A61K048/00;
