METHODS AND KITS FOR DYNAMIC TARGETED HYPERMUTATION

RELATED APPLICATION

This application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 62/644,736, filed on March 19, 2018, and entitled“Methods and Kits for Dynamic Hypermutation,” which is incorporated herein by reference in its entirety for all purposes.

FIELD

Disclosed herein are methodologies and kits for dynamic targeted hypermutation that harness the enzymatic activity of a polynucleic acid-binding protein fused to a nucleobase- editing enzyme to specifically target mutations across a region of interest. These

methodologies and kits facilitate the rapid creation of diverse DNA libraries in vivo or in vitro.

BACKGROUND

Mutagenesis is central to the generation of diverse target gene libraries. Previously described in vitro mutagenesis methodologies allow precise control over sites of mutation; however, they are laborious and time-consuming. Moreover, previously described methodologies directed at the generation of large, diverse libraries in vivo generally act globally on the organism (i.e., they indiscriminately alter DNA sequences in living systems, resulting in undesired off-target mutations). The off-target mutations caused by global mutagenesis result in two major drawbacks in the context of directed evolution. First, they increase the chances of false positives whereby an off-target mutation increases the fitness of an organism and enables“cheating” of the selection process. Second, they result in undesired toxicity due to the off-target mutation of critical genes. These drawbacks require users to carefully optimize global mutagenesis such that the mutation rate is maximized while cellular toxicity is minimized. The careful balance between the number of mutations and cell death constrains mutation rates, ultimately limiting library size and resulting in a lower chance of finding an improved variant and/or a less active final product of the directed evolution process. SUMMARY

Lab-timescale evolution relies on the generation of large mutational libraries to rapidly explore biomolecule sequence landscapes. Although numerous in vitro mutagenesis techniques are available, in vivo mutagenesis is limited (Wong et ah, Comb. Chem. High Throughput Screen. 2006 May; 9(4): 271-88.). Global mutagenesis methods are capable of increasing mutation rates in vivo but unfortunately introduce extensive off-target mutations in essential and cheating genes.

In some aspects the disclosure relates to dynamic targeted hypermutation (DTH), a novel methodology for specifically targeting mutations across a gene of interest. This methodology facilitates the rapid creation of diverse DNA libraries in vivo or in vitro such that increased mutation rates are constrained to the target DNA of interest.

In some aspects the disclosure relates to nucleobase-editing fusion proteins capable of introducing nucleobase mutations in a pre-existing polynucleic acid sequence. In some embodiments, a nucleobase-editing fusion protein comprises a processive polynucleic acid binding protein fused to a nucleobase-editing enzyme.

In some embodiments, the processive polynucleic acid-binding protein of the nucleobase-editing fusion protein comprises the amino acid sequence of an RNA polymerase, a DNA polymerase, a DNA methyltransferase, a DNA glycosylase, or a DNA helicase. In some embodiments, the processive polynucleic acid-binding protein of the nucleobase-editing fusion proteins comprises the amino acid sequence of T7 RNA polymerase or a functional variant thereof.

In some embodiments, the nucleobase-editing enzyme comprises the amino acid sequence of an Apobec protein, a TadA protein, an AMPD protein, a CD A protein, an AD AT protein, an ADAR protein, or a GDA protein. In some embodiments, the nucleobase-editing enzyme comprises the amino acid sequence of an Apobec protein. In some embodiments, the Apobec protein is rApobecl or a functional variant thereof. In some embodiments, the nucleobase-editing enzyme comprises the amino acid sequence of a TadA protein. In some embodiments, the TadA protein is E. coli TadA comprising an A106V mutation and/or a D108N mutation or a protein homolog comprising a homologous mutation(s).

In some aspects, the disclosure relates to methods of performing dynamic targeted hypermutation. In some embodiments, the method comprises contacting at least one polynucleic acid with at least one non-naturally occurring nucleobase-editing fusion protein, wherein: (a) each of the at least one non-naturally occurring nucleobase-editing fusion proteins comprises a processive polynucleic acid-binding protein fused to a nucleobase- editing enzyme; (b) each of the at least one polynucleic acid comprises a target region; and (c) the contacting of the at least one polynucleic acid with the at least one non-naturally occurring nucleobase-editing fusion protein generates mutations at a rate exceeding background mutation rates only in the target region of the at least one polynucleic acid of (b), wherein the background mutation rate of the at least one polynucleic acid of (b) is determined in the absence of the non-naturally occurring nucleobase-editing fusion protein.

In some embodiments, the processive polynucleic acid-binding protein of at least one of the at least one non-naturally occurring nucleobase-editing fusion proteins comprises the amino acid sequence of an RNA polymerase, a DNA polymerase, a DNA methyltransferase, a DNA glycosylase, or a DNA helicase. In some embodiments, the processive polynucleic acid-binding protein of at least one of the at least one non-naturally occurring nucleobase- editing fusion proteins comprises the amino acid sequence of T7 RNA polymerase or a functional variant thereof.

In some embodiments, the nucleobase-editing enzyme of at least one of the at least one non-naturally occurring nucleobase-editing fusion proteins comprises the amino acid sequence of an Apobec protein, a TadA protein, an AMPD protein, a CD A protein, an AD AT protein, an ADAR protein, or a GDA protein. In some embodiments, the nucleobase-editing enzyme of at least one of the at least one non-naturally occurring nucleobase-editing fusion proteins comprises the amino acid sequence of an Apobec protein. In some embodiments, the Apobec protein is rApobecl or a functional variant thereof. In some embodiments, the nucleobase-editing enzyme comprises the amino acid sequence of a TadA protein. In some embodiments, the TadA protein is E. coli TadA comprising an A106V mutation and/or a D108N mutation or a protein homolog comprising a homologous mutation(s).

In some embodiments, each of the at least one polynucleic acid comprises, from 5’ to 3’: a promoter region that is bound by at least one of the at least one non-naturally occurring nucleobase-editing fusion proteins in a sequence- specific manner; the target region; and a terminator region comprising a terminator array.

In some embodiments, the terminator array comprises four or more terminators, optionally four or more T7 UUCG terminators.

In some embodiments, the promoter region of at least one of the at least one polynucleic acids comprises the sequence of SEQ ID NO: 21, SEQ ID NO: 22, and/or SEQ ID NO: 23.

In some embodiments, the contacting of the at least one polynucleic acid with the at least one non-naturally occurring nucleobase-editing fusion protein occurs in a living cell.

In some embodiments, at least one of the at least non-naturally occurring nucleobase- editing fusion proteins is encoded for on a plasmid, wherein the plasmid has copy number of less than 10. In some embodiments, at least one of the at least one non-naturally occurring nucleobase-editing fusion proteins is conditionally expressed in the living cell.

In some embodiments, the living cell contains a modified genome comprising: (a) an integration of a polynucleic acid sequence encoding for and driving the expression of at least one non-naturally occurring nucleobase-editing fusion protein; and/or (b) an integration of a polynucleic sequence comprising, from 5’ to 3’: a promoter region that is bound by at least one of the at least one non-naturally occurring nucleobase-editing fusion proteins in a sequence-specific manner; the target region; and a terminator region comprising a terminator array.

In some embodiments, the living cell contains a modified genome and a plasmid that facilitates expression of a T7 inhibitor, wherein the modified genome of the living cell comprises: (a) an integration of a polynucleic acid sequence encoding for and driving the expression of the non-naturally occurring nucleobase-editing fusion protein, wherein the sequence driving the expression of the fusion protein comprises a sequence bound by Lacl repressor that inhibits transcription of the fusion protein when Lacl is bound; and/or (b) a deletion of genomic sequence encoding for uracil deglycosylase. In some embodiments, the T7 inhibitor is T7 lysozyme.

In some embodiments, the living cell is treated to increase the expression and/or activity of the uracil deglycosylase inhibitor, ugi.

In some aspects, the disclosure relates to kits for performing dynamic targeted hypermutation. In some embodiments, a kit comprises: (a) a polypeptide comprising the amino acid sequence of a non-naturally occurring nucleobase-editing fusion protein comprising a processive polynucleic acid-binding protein fused to a nucleobase-editing enzyme; and (b) a polynucleic acid sequence comprising, from 5’ to 3’: a promoter region that is bound by the non-naturally occurring nucleobase-editing fusion protein of (a) in a sequence-specific manner; a cloning site; and a terminator region comprising a terminator array.

In some embodiments, a kit comprises: (a) a polynucleic acid sequence encoding for and driving the expression of a non-naturally occurring nucleobase-editing fusion protein comprising a processive polynucleic acid-binding protein fused to a nucleobase-editing enzyme; and (b) a polynucleic acid sequence comprising, from 5’ to 3’: a promoter region that is bound by the non-naturally occurring nucleobase-editing fusion protein of (a) in a sequence-specific manner; a cloning site; and a terminator region comprising a terminator array.

In some embodiments, the processive polynucleic acid-binding protein of the non- naturally occurring nucleobase-editing fusion protein comprises the amino acid sequence of an RNA polymerase, a DNA polymerase, a DNA methyltransferase, a DNA glycosylase, or a DNA helicase. In some embodiments, the processive polynucleic acid-binding protein of the non-naturally occurring nucleobase-editing fusion proteins comprises the amino acid sequence of T7 RNA polymerase or a functional variant thereof.

In some embodiments, the nucleobase-editing enzyme of the nucleobase-editing fusion protein comprises the amino acid sequence of an Apobec protein, a TadA protein, an AMPD protein, a CDA protein, an AD AT protein, an ADAR protein, or a GDA protein. In some embodiments, the nucleobase-editing enzyme of the nucleobase-editing fusion protein comprises the amino acid sequence of an Apobec protein. In some embodiments, the Apobec protein is rApobecl or a functional variant thereof. In some embodiments, the Apobec protein is rApobecl or a functional variant thereof. In some embodiments, the nucleobase- editing enzyme comprises the amino acid sequence of a TadA protein. In some

embodiments, the TadA protein is E. coli TadA comprising an A106V mutation and/or a D108N mutation or a protein homolog comprising a homologous mutation(s).

In some embodiments, the terminator array comprises four or more terminators, optionally four or more T7 UUCG terminators.

In some embodiments, the promoter region comprises the sequence of SEQ ID NO: 21, SEQ ID NO: 22, and/or SEQ ID NO: 23.

These and other aspects of the invention are further described below.

BRIEF DESCRIPTION OF THE DRAWINGS

The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present disclosure, which can be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein. It is to be understood that the data illustrated in the drawings in no way limit the scope of the disclosure.

FIGs. 1A-1G. Measurement of targeted mutagenesis capabilities of MutaT7 (an embodiment of a rApol fused to T7 RNA polymerase). FIG. 1A. Schematic demonstrating the differences between global and targeted mutagenesis. FIG. 1B. Diagram depicting the processive cycle through which MutaT7 performs targeted mutagenesis. FIG. 1C. Schematic of a drug resistance start codon reversion reporter assay for measuring extent of mutational targeting to specific loci of DNA. The first gene ( Kan ^R ) reports on-target activity, while the second gene (Te^) reports activity downstream of a DNA spacer element. FIG. 1D. Codon reversion reporter assay data for different combinations of mutagen and reporter elements after 24 hr of culturing. Kanamycin and tetracycline drug resistance frequencies are represented as solid and candy-stripe bars, respectively. FIG. 1E. Extent of off-target mutagenesis assessed by rifampicin drug resistance frequency. FIG. 1F. Cell viability data for populations of cells following expression with different mutagenic constructs (solid bars) or treatment with chemical mutagen (candy-stripe bar). FIG. 1G. Total level of kanamycin resistant colonies following expression with different genetically encoded mutagens for 24 hr. FIGs. 1D-1G. All data reported is the average of biological replicates (n = 3). Error bars represent SEM. Statistically significant comparisons are shown with stars (t-test), while p- values of notable non- significant values are shown as well.

FIGs. 2A-2F. Sequencing-based assessment of mutational targeting by MutaT7 during continuous culturing. FIG. 2A. Diagram of reporter construct and continuous culture experiment to assess mutation accumulation under drift conditions. FIG. 2B. Schematic and representation of mutations observed by Sanger sequencing 96 clones in respective cell populations following 15 days of continuous growth without selection pressure. FIG. 2C. Visual representation of on-target and off-target mutations identified by sequencing episomes propagated in the presence of targeted (MutaT7) and global (MP6) mutagens. Normalized mutation frequency (number of mutations observed divided by number of kb of DNA sequenced in associated regions) and o target to off: target mutation ratio are shown to the right. FIG. 2D. A diagram of continuous culture conditions used to propagate a dual promoter episome in cells expressing mutaT7, along with details for downstream Sanger sequencing analysis work flow. FIG. 2E. A graph of mutations observed by Sanger sequencing target gene from 10 clones at different time points (triangles for total mutations, circles for C to T transitions, squares for G to A transitions). FIG. 2F. Box and whisker plot of mutations from FIG. 2C, where each dot represents a single clone. Mean is represented by horizontal line and fences extend down to minimum and up to maximum.

FIGs. 3A-3B. The deleterious effects of global mutagenesis. FIG. 3A. Global mutagenesis indiscriminately introduces mutations across an organism’s entire genome, introducing mutations in target genes and other genes such as essential genes. Attempts to increase the global mutagenesis rate and thus library diversity lead to decreased cell viability due to off-target mutations in essential genes. Targeted mutagenesis allows for a high mutagenesis rate that does not decrease cell viability by minimizing off-target mutations in essential genes. FIG. 3B. Global mutagenesis can also cause off-target mutations in genes that allow an organism to cheat the selection, thus causing a certain rate of false positives. Targeted mutagenesis minimizes false positives by preventing off-target mutations in genes that allow the organism to cheat the selection.

FIGs. 4A-4B. Multiple terminators required to prevent downstream mutations. FIG. 4A. Reporter plasmids were used that have a kanamycin resistance gene that lacks a start codon downstream from a T7 promoter. The kanamycin resistance gene is followed by a variable number of T7 transcriptional terminators and a tetracycline resistance gene that lacks a start codon. Mutations that revert the ACG codon to an ATG start codon in the kanamycin or tetracycline resistance gene lead to kanamycin or tetracycline resistant colonies, respectively. FIG. 4B. After growing the reporter plasmid in the MutaT7 strain for 24 hours, the frequency of kanamycin resistant colonies is relatively constant regardless of the number of terminators between the kanamycin and tetracycline resistance genes. The frequency of tetracycline resistant colonies decreases as more terminators are introduced between the kanamycin and tetracycline genes. After about 4 terminators, the tetracycline resistance frequency is at background resistance levels (as determined by a drApol-T7 strain negative control). This suggests that an array of terminators is able to stop T7 transcription and thus MutaT7 mutations downstream from the terminator array.

FIG. 5. Mutation assay workflow. The mutation assay workflow is shown. Glycerol stocks of each sample are streaked on LB agar with appropriate antibiotics and grown at 37°C for 24 hours. Then, single colonies are picked in triplicate and grown in LB with appropriate antibiotics and inducers of mutagenesis at 37°C for 24 hours. Then, 1 mL aliquots of each culture are pelleted and resuspended in LB to remove antibiotics and inducers. The resuspension is then plated at various dilutions on plates with various antibiotics to test the mutation rate and a metabolic dye, tetrazolium chloride, for contrast during imaging. After growing at 37°C for 48 hours, the plates are imaged on a document scanner at 400 d.p.i. and colonies are counted using the OpenCFU (3.9.0) software (Geissmann et al., PLoS One.

2013; 8(2): e54072).

FIG. 6. Optimizing antibiotic concentrations for the mutation assay. At

concentrations of less than 200 mg/mL, small colonies (black arrows) appeared on LB + kanamycin + tetrazolium chloride plates with DH10B carrying the reporter plasmid. The small colonies could be present due to a low level of expression of the kanamycin resistance gene through translation initiation from the ACG start codon (Hecht et ah, Nucleic Acids Res. 2017 Apr 20; 45(7): 3615-26). On plates with 200 mg/mL kanamycin, the small colonies on the DH10B plate do not appear after 48 hours. The number of colonies on plates of MutaT7 cells with the reporter plasmid were similar between plates with 150 mg/mL and 200 mg/mL kanamycin.

FIGs. 7A-7D. Additional mutation assay data. FIG. 7A. Additional kanamycin, tetracycline and FIG. 7B rifampicin resistance frequency data for Aung and drApol negative control strains with various reporter plasmids. FIG. 7C. Fosfomycin resistance frequency data shows a high mutagenesis rate only in the presence of MP6, suggesting that neither MutaT7 nor the negative controls mutagenize the E. coli genome appreciably. FIG. 7D. Additional ampicillin resistance frequency data suggests that neither the Aung nor the drApol negative control strains suffer from low cell viability.

FIG. 8. Kanamycin and tetracycline resistance frequencies without the reporter plasmids. To ensure that the kanamycin and tetracycline resistant colonies in the mutation assay are due to mutations in the reporter plasmid and not mutations in the genome, the MP6 strain and MutaT7 strain were grown for 24 hours without reporter plasmids in LB with 100 mg/mL streptomycin and 25mM arabinose (with 10 mg/mL chloramphenicol for the MP6 strain). After washing once with LB, 50 mί of each culture was plated on LB with 50 mg/mL tetrazolium chloride and 30 mg/mL kanamycin, 200 mg/mL kanamycin or 20 mg/mL tetracycline. The lack of colonies on plates with 200 mg/mL kanamycin or 20 mg/mL tetracycline suggests that almost all the colonies in the mutation assay at these concentrations are due to mutations in the reporter plasmid. However, at lower kanamycin concentrations, kanamycin resistance colonies appear in the MP6 strain, suggesting that mutations are occurring in the genome of MP6 that can confer moderate kanamycin resistance.

FIGs. 9A-9B. Promoter design. FIG. 9A. The P _Aiiac o-i promoter has been engineered to have minimal leaky expression when repressed with lacl (Camsund et ah, J. Biol. Eng. 2014 Jan 27; 8(1): 4). The BBa_J23l l4 promoter (SEQ ID NO: 16) from the Anderson Collection (parts.igem.org/Promoters/Catalog/Anderson) has been shown to have about a tenth of the strength of the s ⁷⁰ consensus binding sites. With the intention of obtaining a weak, strongly repressed promoter, the s ⁷⁰ binding sites of BBa_J23114 (SEQ ID NO: 16) were grafted onto_PAiiaco-i (SEQ ID NO: 93) to yield PAiiaco-Tenth (SEQ ID NO: 24) (changes include TTGAC [SEQ ID NO: 25] to TTTAT [SEQ ID NO: 26] at -35, GAT ACT [SEQ ID NO: 27] to TACAAT [SEQ ID NO: 28] at -10). FIG. 9B. In order to increase the expression of lacl from the DH10B genome, the endogenous V _\aci promoter (SEQ ID NO: 94) was replaced with the strong, constitutive R, _ίίG promoter (SEQ ID NO: 95) to yield the Pi _adO P _tac promoter (SEQ ID NO: 96) (Glascock C.B. and Weickert M.J., Gene. 1998 Nov 26; 223(1- 2): 221-31).

FIGs. 10A-10C. Catalytically dead rApol. FIG. 10A. A clustalw (Larkin et al., Bioinformatics. 2007 Nov 1; 23(21): 2947-48) alignment of rApol (SEQ ID NO: 97) and another cytidine deaminase, human activation-induced cytidine deaminase (hAID) (SEQ ID NO: 98), is shown. Highlighted are aligned glutamate residues that have been shown to be critical for rApol activity (E63) (Navaratnam et al., Cell. 1995 Apr 21; 81(2): 187-95) and hAID activity (E58) (Ma et al., Nat. Methods. 2016 Dec; 13(12): 1029-35). FIG. 10B. A crystal structure of a catalytically dead E58A mutant of hAID (PDB: 5W0ET) is shown with dCMP in the active site. The position of E58 is shown based off of an alignment between 5W0ET and a crystal structure of wild-type hAID with an empty active site (PDB: 5W0Z) (Qiao et al., Mol. Cell. 2017 Aug 3; 67(3): 361-73). E58 is positioned closely to the dCMP substrate. FIG. 10C. A proposed catalytic mechanism of hAID cytidine deamination

(Chaudhuri J. and Alt F.W., Nat. Rev. Immunol. 2004 Jul; 4(7): 541-52) based on studies with the E. coli cytidine deaminase (Betts et al., J. Mol. Biol. 1994 Jan 14; 235(2): 635-56) is shown. The role of E58 in proton shuttling is shown. The critical E63 residue in rApol likely plays a similar role.

FIGs. 11A-11B. Inducible expression of MutaT7. FIG. 11A. Schematic of inducible constructs demonstrating the expected outcomes for populations of cells following 24 hours of culturing while expressing constructs that are non-mutagenic (drApol-T7), targeted (MutaT7), or globally mutagenic (rApol). FIG. 11B. Data for kanamycin drug resistance frequencies in response to increasing levels of IPTG treatment for 24 hours. Kanamycin reports on-target mutagenesis, and data reported is the average of biological replicates (n = 3). Error bars represent SEM.

FIGs. 12A-12B. FIG. 12A. Schematic illustrating global versus targeted mutagenesis. FIG. 12B. The MutaT7 construct and the targeted mutagenesis cycle.

FIGs. 13A-13E. FIG. 13A. Drug resistance start codon reversion reporter assay for measuring extent of mutagenesis at specific DNA loci. FIG. 13B. Codon reversion reporter assay data for combinations of mutagen and reporter plasmids. Mutagens include deactivated rApol fused to T7 RNA polymerase (drApol-T7; negative control), unfused rApol (rApol), targeted mutagen (MutaT7), and global mutagen (MP6). FIG. 13C. Extent of off-target mutagenesis assessed by rifampicin resistance assay for populations carrying the codon reversion reporter plasmid with a terminator array in FIG. 13B (EMS = ethyl

methanesulfonate). FIG. 13D. Viability data for cell populations in FIG. 13B, along with drApol-T7 populations treated with EMS. FIG. 13E. Total number of kanamycin resistant colonies for populations in FIG. 13B. Values represent mean of independent experiments (n = 3); error bars represent s.e.m.; statistical significance was evaluated by a Student’s t-test: *p < 0.05, **p < 0.01 and ***p < 0.001; notable non-significant p-values shown.

FIGs. 14A-14C. FIG. 14A. Reporter construct and continuous culture experiment to assess mutation accumulation under drift conditions. FIG. 14B. On-target (oval) and off- target (x) mutations identified by sequencing episomes propagated in the presence of targeted (MutaT7) and global (MP6) mutagens. FIG. 14C. Normalized mutation frequency (number of mutations observed divided by kb of DNA sequenced in associated regions) for data in FIG. 14B.

FIGs. 15A-15B. MutaT7 maintains a high level of activity and processivity. FIG.

15A. A general diagram of the lacZa reporter plasmid C1E, which has both a“near” and “far” T7 promoter. The rest of the lacZa reporter plasmids are missing one or both of these T7 promoters, or have a strong, constitutive P _tac promoter in place of the“near” T7 promoter. The genome of human adenovirus type 5 serves as the intervening DNA between the“near” and“far” promoters. FIG. 15B. FacZa activity measured via oNPG cleavage. ung ⁺ served as a negative control that lacks the T7 RNA polymerase.“drApol+T7 ung ⁺ ” served as a positive control in which deactivated rApol and active T7 are expressed as separate proteins. Various reporters were used with different locations of targeted (T7) promoters and constitutive (Ptac) promoters, as indicated by the key on the x-axis.“FB Only” was a negative control in which FB with no cells was added to the assay mixture. FIGs. 16A-16B. Promoter design. FIG. 16A. The P _Aiiac o i promoter has been engineered to have minimal leaky expression when repressed with lacl (Camsund et al., J. Biol. Eng. 2014 Jan 27; 8(1): 4). The BBa_J23 l l4 promoter (SEQ ID NO: 16) from the Anderson Collection (Available: parts.igem.org/Promoters/Catalog/Anderson) has been shown to have about 1/10 of the strength of the s ⁷⁰ consensus binding sites. With the intention of obtaining a weak, strongly repressed promoter, the s ⁷⁰ binding sites of

BBa_J23 l l4 were grafted onto PAiiacO-i (SEQ ID NO: 93) to yield PAiiacO-Tenth (SEQ ID NO: 24) (changes include TTGAC [SEQ ID NO: 25] to TTTAT [SEQ ID NO: 26] at -35, GATACT [SEQ ID NO: 27] to TACAAT [SEQ ID NO: 28] at -10). FIG. 16B. In order to increase the expression of lacl from the DH10B genome, the endogenous V _\aci promoter (SEQ ID NO: 94) was replaced with the strong, constitutive R, _ίίG promoter (SEQ ID NO: 95) to yield the Pi _adO P _tac promoter (SEQ ID NO: 96) (Glascock C.B. and Weickert M.J., Gene. 1998 Nov 26; 223(1-2): 221-31).

FIG. 17. Mutation assay workflow. The mutation assay workflow is shown. Glycerol stocks of each sample were streaked on LB agar with appropriate antibiotics and grown at 37 °C for 24 h to obtain clones. Single colonies were picked in triplicate and grown in LB with appropriate antibiotics and inducers of mutagenesis at 37 °C for 24 h to accumulate mutations. 1 mL aliquots of each culture were pelleted and resuspended in LB to remove antibiotics and inducers. The resuspension was plated at various dilutions on plates with various antibiotics to analyze the mutation rates and cell viability. The plates also contained a metabolic dye, tetrazolium chloride, for contrast during imaging. After incubating at 37 °C for 48 h, the plates were imaged on a document scanner at 400 d.p.i. and colonies were counted using the OpenCFU (3.9.0) software (Geissmann, PLoS One. 2013; 8(2): e54072).

FIG. 18. Optimizing antibiotic concentrations for mutation assays. At concentrations of less than 200 pg/mL, small colonies (black arrows) appeared on LB + kanamycin + tetrazolium chloride plates with DH10B carrying the reporter plasmid. The small colonies theoretically may have been present owing to a very low level of expression of the kanamycin resistance gene through translation initiation from the ACG start codon (Hecht et al., Nucleic Acids Res. 2017 Apr 20; 45(7): 3615-26). On plates with 200 pg/mL kanamycin, the small colonies on the DH10B plate did not appear even after 48 h. The number of colonies on plates of MutaT7 cells (TABLE 8) with the reporter plasmid were similar between plates with 150 pg/mL and 200 pg/mL kanamycin. At a concentration of 20 pg/mL tetracycline, no colonies appeared on LB + tetracycline + tetrazolium chloride plates with DH10B cells carrying the reporter plasmid, while many colonies appeared in MutaT7 cells carrying the reporter plasmid.

FIGs. 19A-19D. Additional mutation assay data with negative control strains and fosfomycin resistance data. FIG. 19A. Kanamycin and tetracycline resistance frequency data for Aung and drApol negative control strains (TABLE 8) with various reporter plasmids suggest that nei-ther strain mutagenizes the reporter plasmid appreciably. Experiment performed as in FIG. 13B with the indicated strains. FIG. 19B. Rifampicin resistance frequency data for Aung and drApol negative control strains with various reporter plasmids suggest that neither strain mutagenizes the E. coli genome appreciably. Experiment performed as in FIG. 13C with the indicated strains. FIG. 19C. Fosfomycin resistance frequency data show a high mutagenesis rate only in the presence of MP6, suggesting that neither MutaT7 (TABLE 8) nor the negative controls mutagenize the E. coli genome appreciably. Experiment performed as in FIG. 13C except cells were plated on LB-agar with 100 pg/mL fosfomycin and 50 pg/mL tetrazolium chloride. FIG. 19D. Ampicillin resistance frequency data suggest that neither the Aung nor drApol negative control strains suffer from low cell viability. Experiment performed as in FIG. 13D with the indicated strains.

FIG. 20. Multiple T7 terminators prevent downstream mutations. After growing the reporter plasmid in the MutaT7 strain (TABLE 8) for 24 h, the frequency of kanamycin resistant mutant colonies was relatively constant regardless of the number of terminators between the kanamycin and tetracycline resistance genes. The frequency of tetracycline resistant colonies decreased as more T7 terminators were introduced. After four T7 terminators were added, the tetracycline re-sistance frequency was restored to background levels (as evaluated using a drApol-T7 strain as a negative control; TABLE 8).

FIGs. 21A-21B. Directed evolution of folA using MutaT7 results in a lower false positive frequency than is obtained using a global mutagen. FIG. 21A. Schematic of a directed evolution experiment on folA (promoter and protein coding sequence of

dihydrofolate reductase from E.coli ) designed to measure the frequency of true and false positives following mutagenesis and selection with trimethoprim (TMP). Clones propagating an episome with wild-type fo IA downstream of a T7 promoter were mutagenized with MutaT7 or a global mutagen (MP6) in the absence of selection pressure. Selection on LB- agar plates with TMP enabled isolation of TMP-resistant colonies. Subsequent amplification and Sanger sequencing of episomal/o/A genes is used to assess the frequency of true positives (drug-resistant mutations in episomal/o/A) and false positives (drug-resistant mutations somewhere else in genome). FIG. 21B. Summary of bacterial growth curve data measuring extent of TMP resistance in evolved isolates. Growth rates in response to increasing concentrations of TMP were determined for a representative isolate from each biological replicate along with a positive control (episomal/o/A, but with a strong promoter instead of wild-type promoter) and a negative control (drApo-T7 with episomal/o/A). After determining maximal growth rate within each sample, growth rates were normalized to the highest rate within each sample series, yielding the relative growth rate (y-axis) at each TMP concentration (x-axis).

FIG. 22. Sanger sequencing reveals mutations throughout the target region.

Schematic and representation of mutations observed by Sanger sequencing 96 clones in the indicated cell populations following 15 d of continuous growth in the absence of selection pressure.

FIGs. 23A-23B. MutaT7 introduced mutations throughout the rpsL gene. FIG. 23 A. Schematic of streptomycin resistance counter- selection assay, which is designed to enrich for mutations that nullify streptomycin sensitivity. Such sensitivity is initially conferred by a streptomycin-sensitive allele of rpsL downstream of a T7 promoter on a reporter plasmid. FIG. 23B. The position of various mutations throughout the T7 promoter + rpsL reporter plasmid determined by Sanger sequencing of 48 streptomycin resistant mutants from the MP6 strain and 42 streptomycin resistant mutants from the MutaT7 strain.

FIGs. 24A-24C. Dual T7 promoters introduce mutations in both strands. FIG. 24A. Diagram of continuous culture conditions used to propagate a dual promoter episome in cells expressing MutaT7, along with details for downstream Sanger sequencing analysis. FIG.

24B. Graphic of mutations observed by Sanger sequencing a target gene between dual opposing T7 promoters from clones harvested at different time points (triangles for total mutations, circles for C to T transitions, and squares for G to A transitions). FIG. 24C. Box and whisker plot of mutations from FIG. 24B, where each dot represents the number of mutations found in each clone. Mean number of mutations at each time point is represented by horizontal line.

FIGs. 25A-25C. Ugi expression increases mutagenesis by inhibiting dU to dC repair. FIG. 25 A. Kanamycin resistance frequency data for the ugi rApol and ugi drApol-T7 negative control strains and the ugi MutaT7 mutagenic strain (TABLE 8) with various reporter plasmids show that the ugi protein can increase mutagenesis when expression of ugi and MutaT7 from the PAiiaco-Tenth promoter is induced with IPTG. FIG. 25B. Tetracycline resistance frequency data for the same experiment performed in FIG. 25A. FIG. 25C. Cell viability as determined by the number of ampicillin resistance colonies for the same experiment performed in FIG. 25 A.

FIGs. 26A-26D. FIG. 26A. Schematic of a drug resistance premature stop codon reversion reporter assay for measuring extent of mutational targeting via mutations in the Kan ^R or Tet ^R genes. FIG. 26B. Premature stop codon reversion frequencies with different mutagenic constructs. N.D. means mutants were not detected. FIG. 26C. Global off-target mutagenesis assessed by rifampicin resistance frequencies.“Not Collected” means that the rifampicin resistance was not measured for these samples. FIG. 26D. Cell viability measured by colony forming units (CFU) on plates with ampicillin and streptomycin.

DETAILED DESCRIPTION

Traditional in vivo mutagenesis strategies, which are especially important for studying and using evolution in living systems, rely on exposing organisms to exogenous mutagens (e.g., high energy light or chemicals (Cupples C.G. and Miller J.H., Proc. Natl. Acad. Sci. U.S.A. 1989 Jul; 86(14): 5345-49; Tessman et al., Science. 1965 Apr 23; 148(3669): 507-8)) or expressing mutagenic enzymes in organisms with deficient repair machinery (e.g., XL1- Red (Greener et al., Mol. Biotechnol. 1997 Apr; 7(2): 189-95) or the MP6 plasmid (Badran A.H. and Liu D.R., Nat. Commun. 2015 Oct 7; 6: 8425). These global mutagenesis strategies can yield high mutation rates and diverse genetic landscapes. However, the extensive occurrence of mutations throughout the genome is problematic for many experiments, especially directed evolution (FIG. 1A). Off-target mutations outside the intended DNA region are often toxic when they occur in the many essential portions of the genome (Gerdes et al., J. Bacteriol. 2003 Oct; 185(19): 5673-84; Wang et al., Science. 2015 Nov 27;

350(6264): 1096-101), a problem that can severely limit library size and even lead to rapid silencing of mutagenic plasmids. Moreover, global mutagens potentiate the emergence of “parasite” variants outside the gene of interest that can circumvent selection schemes (Badran A.H. and Liu D.R., Curr. Opin. Chem. Biol. 2015 Feb; 24: 1-10). Targeted in vivo mutagenesis strategies have the potential to overcome these deficiencies. For example, DNA-damaging enzymes fused to deactivated Cas9 nucleases can edit bases at specific genetic loci while minimizing off-target mutations (Komor et al., Nature. 2016 May 19; 533(7603): 420-24). Such methods enable targeting of diverse genomic sites but require significant engineering to tile mutagenic enzymes throughout the target DNA (Hess et ah,

Nat. Methods. 2016 Dec; 13(12): 1036-42), engineering that must be repeated after each successive round of evolution.

As described herein, Dynamic Targeted Hypermutation (DTH) involves the implementation of a nucleobase-editing enzyme to create genetic diversity in a specific target region of a polynucleic acid sequence. In some embodiments, the methodology facilitates continuous directed evolution in a living system. By mutating specific regions of a polynucleic acid in a targeted fashion, these methodologies reduce off-target mutations that result in cell death or“cheating” of the selection scheme in the directed evolution platform (FIG. 1A). This reduction of off-target mutagenesis results in the production of sequence libraries of unprecedented scale with fewer false positives due to cheating, which translates to an increased probability of discovering an improved product or to the discovery of better final products of the continuous directed evolution process in a shorter amount of time.

In some aspects, the disclosure relates to nucleobase-editing fusion proteins. The nucleobase editing enzymes described herein are capable of altering nucleobases of (or introducing nucleobase mutations in) a pre-existing polynucleic acid sequence (as

distinguished from the introduction of mutations during polynucleic acid synthesis, which leaves the parent strand unchanged). In some embodiments, the nucleobase-editing fusion protein can introduce mutations in the 5’ to 3’ direction of a polynucleic acid sequence. In some embodiments, the nucleobase-editing fusion protein can introduce mutations in the 3’ to 5’ direction of a polynucleic acid sequence. In some embodiments, the nucleobase enzyme can introduce mutations in the 5’ to 3’ and the 3’ to 5’ direction of a polynucleic acid sequence. In some embodiments, a nucleobase-editing fusion protein comprises a

polynucleic acid-binding protein fused to a nucleobase-editing enzyme.

As used herein, the term“polynucleic acid-binding protein” refers to a protein that binds to specific polynucleic acid sequences. Examples of DNA binding proteins are known to those having skill in the art and include, but are not limited to, polymerases, ligases, reverse transcriptases, nucleases, methyltransferases, glycosylases, helicases, transcription factors, and transcription repressors.

In some embodiments, the polynucleic-acid binding protein is a processive enzyme. The term“processive enzyme” as used herein refers to an enzyme that catalyzes consecutive reactions without releasing its substrate (e.g., in the context of a polymerase, processivity relates to the average number of nucleotides added by the polymerase enzyme per association event with the template strand). Examples of processive enzymes include, but are not limited to, RNA polymerases, DNA polymerases, DNA methyltransferases, DNA glycosylases, and DNA helicases. In some embodiments, the processive enzyme is an RNA polymerase, a DNA polymerase, a DNA methyltransferase, a DNA glycosylase, a DNA helicase, or a functional variant thereof. In some embodiments, the processive enzyme is an RNA polymerase. Examples of RNA polymerases are known to those having skill in the art and include, but are not limited to, T7 RNA polymerase, T3 RNA polymerase, and SP6 RNA polymerase. In some embodiments, the processive enzyme is T7 RNA polymerase or a functional variant thereof.

As used herein, the term“nucleobase-editing enzyme” refers to an enzyme that catalyzes the conversion of a nucleobase to a different nucleobase. Examples of nucleobase- editing enzymes are known to those having skill in the art and include, but are not limited to, Apobec proteins (conversion of cytosine to uracil), TadA proteins (conversion of adenosine to inosine), AMPD proteins (conversion of adenosine to inosine), CDA proteins (conversion of cytidine to uridine), AD AT proteins (conversion of adenosine to inosine), ADAR proteins (conversion of adenosine to inosine), ADA proteins (conversion of adenosine to inosine), and GDA proteins (conversion of guanine to xanthine). In some embodiments, the nucleobase- editing enzyme is selected from the group consisting of an Apobec protein, a TadA protein, an AMPD protein, a CDA protein, an AD AT protein, an ADAR protein, a GDA protein, or a functional variant thereof.

As used herein, the term“Apobec protein” refers to a protein family of deaminases, capable of mutagenizing DNA and/or RNA through the conversion of cytosine to uracil. Apobec proteins have been identified in various species and are known to those having skill in the art. For example, human genes encoding an Apobec protein include APOBEC 1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3D (or APOBEC3E), APOBEC3F, APOBEC3G, APOBEC3H, APOBEC4, and Activation-Induced cytidine deaminase. The ability of Apobec proteins to mutagenize DNA and/or RNA varies. For example, some Apobec proteins appear to lack deaminase activity (e.g., APOBEC2). Others are highly mutagenic (e.g., APOBEC3G and rApobecl). The term“Apobec protein” as used herein encompasses all known and currently identifiable Apobec proteins and functional variants thereof. In some embodiments, the Apobec protein is rApobecl or a functional variant thereof. As used herein, the term“TadA protein” refers to a family of tRNA-specific adenosine deaminases. TadA proteins have been identified in various species and are known to those having skill in the art. For example, human genes encoding a TadA protein include ADAT1 and ADAT2. E. coli TadA and mouse ADA are additional examples. In some embodiments, the TadA protein is ADAT1, ADAT2, E. coli TadA, ADA, or a functional variant thereof.

As used herein, the term“AMPD protein” refers to a family of adenosine deaminases. AMPD proteins have been identified in various species and are known to those having skill in the art. For example, human genes encoding an AMPD protein include AMPD1, AMPD2 and AMPD3. In some embodiments, the AMPD protein is AMPD1, AMPD2, AMPD3, or a functional variant thereof.

As used herein, the term“CDA protein” refers to a family of cytidine deaminases. CDA proteins have been identified in various species and are known to those having skill in the art. For example, human genes encoding a CDA protein include CDA. In some embodiments, the CDA protein is human CDA or a functional variant thereof.

As used herein, the term“ADAR protein” refers to a family of adenosine deaminases. ADAR proteins have been identified in various species and are known to those having skill in the art. For example, human genes encoding an ADAR protein include ADAR1 and

ADAR2. In some embodiments, the ADAR protein is ADAR1, ADAR2 or a functional variant thereof.

As used herein, the term“GDA protein” refers to a family of guanine deaminases. GDA proteins have been identified in various species and are known to those having skill in the art. For example, human genes encoding a GDA protein include GDA. In some embodiments, the GDA protein is human GDA or a functional variant thereof.

The term“functional variant” includes polypeptides which are about 70% identical, at least about 80% identical, at least about 90% identical, at least about 95% identical, at least about 98% identical, at least about 99% identical, at least about 99.5% identical, or at least about 99.9% identical to a protein’s native amino acid sequence (i.e., wild-type amino acid sequence) and which retain functionality.

The term“functional variant” also includes polypeptides which are shorter or longer than a protein’s native amino acid sequence by about 5 amino acids, by about 10 amino acids, by about 15 amino acids, by about 20 amino acids, by about 30 amino acids, by about 40 amino acids, by about 50 amino acids, by about 75 amino acids, by about 100 amino acids or more and which retain functionality.

In the context of a processive polynucleic-acid binding protein, the term“retain functionality” refers to a functional variant’s ability to catalyze consecutive reactions without releasing its substrate at least about 5%, 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90%, 100%, or more than 100% as efficiently as the respective non-variant (i.e., wild- type) processive polynucleic-acid binding protein. Methods of measuring and comparing processivity are known to those skilled in the art.

In the context of a nucleobase-editing enzyme, the term“retain functionality” refers to a functional variant’s ability to catalyze the conversion of a nucleobase to a different nucleobase at least about 5%, 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90%, 100%, or more than 100% as efficiently as the respective non-variant (i.e., wild-type) protein. Methods of measuring and comparing nucleobase conversion rates are known to those having skill in the art.

As used herein, the term“fusion protein” refers to the coupling of two or more polypeptides/peptides. In some embodiments, a fusion protein comprises two or more polypeptides/peptides that are covalently coupled in a single polypeptide chain. Covalently connected fusion proteins typically are produced genetically through the in-frame fusing of the nucleotide sequences encoding for each of the said polypeptides/peptides. Expression of the fused coding sequence results in the generation of a single protein without any

translational terminator between each of the polypeptides/peptides. In some embodiments, a fusion protein comprises two or more polypeptides/peptides that are coupled through non- covalent association, such as through dimerization domains like FKBP and FRB which dimerize upon the addition of a small-molecule, rapamycin (DeRose et ah, Pflugers Arch. 2013 Mar; 465(3): 409-17). For example, in some embodiments, the polynucleic-acid binding protein is covalently coupled to FKBP and the nucleobase-editing enzyme is covalently coupled to FRB, which could dimerize (non-covalent association) in the presence of rapamycin. Examples of other dimerizing domains or adaptor proteins that facilitate non- covalent association are known to those having skill in the art.

The nucleobase-editing fusion proteins described and encompassed herein comprise a polynucleic acid-binding protein fused to a nucleobase-editing enzyme. In some

embodiments, the nucleobase-editing enzyme is C-terminal to the polynucleic acid-binding protein. In other embodiments, the nucleobase-editing enzyme is N-terminal to the polynucleic acid-binding protein.

In some embodiments, the nucleobase-editing fusion protein comprises more than one nucleobase-editing enzyme and/or more than one polynucleic acid-binding protein, which can be arranged in any manner. For example, a nucleobase-editing fusion protein comprising two nucleobase-editing enzymes (“E”) and one polynucleic acid-binding protein (“B”) may be structured from N-terminus to C-terminus as follows: (i) E-B-E; (ii) E-E-B; or (iii) B-E-E.

In some embodiments, one or more proteins or protein domains are positioned between the fused polynucleic acid-binding protein and the nucleobase-editing enzyme. In some embodiments, the polynucleic acid-binding protein is fused to the nucleobase-editing enzyme through a linker. As used herein, the term“linker” refers to a flexible molecule used to connect two molecules of interest together. In some embodiments, the linker is a hydrophilic linker (e.g., PEG linker). In some embodiments, the linker is a peptide linker. In some embodiments, the peptide linker is an XTEN linker (Schellenberger et ah, Nat.

Biotechnol. 2009 Dec; 27(12): 1186-90) or a (GGS) _n linker.

In some embodiments, the polynucleic acid-binding protein and the nucleobase- editing enzyme are fused via one or more of the following: (i) a cysteine-cysteine disulfide bond; (ii) intein splicing; and (iii) a covalent linkage from an unnatural amino acid (e.g., alkyne-azide“click” reactions, olefin metathesis, or oxime ligation). In some embodiments, the polynucleic acid-binding protein and the nucleobase-editing enzyme are fused through exposure to cross-linking reagents that react with amino acid side chains, such as perfluoro- aromatic stapling, or reagents like NHS esters or isothiocynates or aldehydes.

In some aspects, the disclosure relates to methods of performing dynamic targeted hypermutation. In some embodiments, the method comprises contacting at least one polynucleic acid with at least one non-naturally occurring nucleobase-editing fusion protein as described above, wherein: (a) each of the at least one non-naturally occurring nucleobase- editing fusion proteins comprises a polynucleic acid-binding protein fused to a nucleobase- editing enzyme; (b) each of the at least one polynucleic acid comprises a target region; and (c) the contacting of the at least one polynucleic acid with the at least one non-naturally occurring nucleobase-editing fusion protein generates mutations at a rate exceeding background mutation rates only in the target region of the at least one polynucleic acid of (b), wherein the background mutation rate of the at least one polynucleic acid of (b) is determined in the absence of the non-naturally occurring nucleobase-editing fusion protein. As used herein, the term“nucleic acid,” as used herein, refers to a compound comprising a nucleobase and an acidic moiety (e.g., a nucleoside, a nucleotide, or a polymer of nucleotides). As used herein, the terms“polynucleic acid” or“polynucleic acid molecule” are used interchangeably and refer to polymeric nucleic acids (e.g., nucleic acid molecules comprising three or more nucleotides that are linked to each other via a phosphodiester linkage).

Polynucleic acid molecules have various forms. In some embodiments, the polynucleic acid molecule is DNA. In some embodiments, the polynucleic acid molecule is double-stranded DNA. For example, in some embodiments, the DNA is genomic DNA. In some embodiments, the DNA is plasmid DNA. In other embodiments, the polynucleic acid molecule is single- stranded DNA. In some embodiments, the polynucleic acid molecule is RNA. In some embodiments, the polynucleic acid molecule is double-stranded RNA. In other embodiments, the polynucleic acid molecule is single-stranded RNA. In some embodiments, the polynucleic acid is a hybrid between DNA and RNA.

The term“target region” as used herein refers to the polynucleic acid sequence that one seeks to mutagenize. In some embodiments, the target region comprises a gene-coding polynucleic acid sequence. In some embodiments, the gene-coding polynucleic acid sequence encodes for an entire gene or sets of entire genes (e.g., a bacterial operon). In other embodiments, the gene-coding polynucleic acid sequence encodes for a portion of a gene (e.g., a polynucleic acid sequence encoding for a protein domain). As used herein the term “portion of a gene” refers to a polynucleic acid sequence comprising at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of a gene-coding polynucleic acid sequence.

In some embodiments, the target region comprises a non-coding nucleic acid sequence. In some embodiments, the non-coding nucleic acid sequences comprises the sequence of a regulatory element, an intron, a non-coding functional RNA, a repeat sequence, or a telomere. In some embodiments, the regulatory element is selected from the group consisting of an operator, an enhancer, a silencer, a promoter, a terminator, or an insulator. In some embodiments, the target region comprises a gene-coding and non-coding segment of DNA.

The length of a target region may vary. For example, in some embodiments, the target region is greater than 10,000 nucleotides or base pairs in length, such as at least 20,000, at least 25,000, at least 30,000, at least 40,000, at least 50,000, at least 60,000, at least 70,000, at least 80,000, at least 90,000, at least 100,000, or more nucleotides or base pairs in length.

In other embodiments, the target region is between 100 and 10,000 nucleotides or base pairs in length, such 100-200, 200-500, 500-1000, or 1,000-5,000 nucleotides or base pairs in length. In other embodiments, the polynucleic acid molecule region of interest is less than 100 nucleotides or base pairs in length.

In some embodiments, a nucleobase-editing fusion protein generates mutations at a rate exceeding background mutation rates only in the target region (i.e., in polynucleic acid regions outside of the target region, the conversion of cytosine bases to uracil bases remain at background levels). In other embodiments, mutation rates outside of the target region (i.e., background mutation rates) are increased less than 100 percent, less than 90 percent, less than 80 percent, less than 70 percent, less than 60 percent, less than 50 percent, less than 40 percent, less than 30 percent, less than 20 percent, or less than 10 percent in the presence of the nucleobase-editing fusion protein relative to the rate in the absence of the nucleobase- editing fusion protein. Processes contributing to background mutation rates include the spontaneous deamination of cytosine to uracil through hydrolysis and errors in replication or transcription. Methods of measuring mutation rates are known to those having skill in the art.

In some embodiments, the at least one polynucleic acid comprises, from 5’ to 3’: a promoter region that is bound by at least one of the at least one non-naturally occurring nucleobase-editing fusion proteins in a sequence- specific manner; the target region; and a terminator region comprising a terminator array.

In some embodiments, the promoter region of at least one of the at least one polynucleic acids comprises the sequence of SEQ ID NO: 21, SEQ ID NO: 22, and/or SEQ ID NO: 23.

In some embodiments, the terminator array comprises four or more terminators, such as at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten terminators. In some embodiments, Rho-independent terminators are used, which can be one or more types of naturally occurring terminators, such as T7 and rmB, or one or more types of engineered high-efficiency terminators, such as TO. In some embodiments, when using a nucleobase-editing fusion protein containing T7 RNA polymerase, the terminator array comprises at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten T7 UETCG terminators.

In some embodiments, the contacting of the at least one polynucleic acid with the at least one non-naturally occurring nucleobase-editing fusion protein occurs in a living cell. In some embodiments, the living cell is a cell of a multicellular organism. In some embodiments the living cell is a unicellular organism. In some embodiments, the unicellular organism is a bacteria. In some embodiments, the bacteria is E. coli.

In some embodiments, the nucleobase-editing fusion protein is encoded for on a plasmid contained within a living cell, wherein the plasmid has copy number of less than 10. In some embodiments the copy number is less than 9, less than 8, less than 7, less than 6, less than 5, less than 4, less than 3, or less than 2.

In some embodiments, the living cell contains a modified genome comprising an integration of a polynucleic acid sequence encoding for and driving the expression of the non-naturally occurring nucleobase-editing fusion protein. In some embodiments, the expression of the non-naturally occurring nucleobase-editing fusion protein is driven by a promoter comprising the sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, and/or SEQ ID NO: 24.

In some embodiments, the living cell contains a modified genome comprising an integration of a polynucleic sequence comprising, from 5’ to 3’: a promoter region that is bound by at least one of the at least one non-naturally occurring nucleobase-editing fusion proteins in a sequence- specific manner; the target region; and a terminator region comprising a terminator array.

In some embodiments, the living cell contains a modified genome comprising: an integration of a polynucleic acid sequence encoding for and driving the expression of the non-naturally occurring nucleobase-editing fusion protein; and an integration of a polynucleic sequence comprising, from 5’ to 3’: a promoter region that is bound by at least one of the at least one non-naturally occurring nucleobase-editing fusion proteins in a sequence-specific manner; the target region; and a terminator region comprising a terminator array.

In some embodiments, the expression of at least one of the at least one non-naturally occurring nucleobase-editing fusion proteins can be conditionally controlled. Examples of inducible expression systems that facilitate conditional gene expression are known to those having skill in the art. For example, some inducible expression systems comprise promoters that are chemically regulated (e.g., alcohol-regulated, tetracycline-regulated, steroid- regulated, or metal-regulated. Other inducible expression systems comprise promoters that are physically regulated (e.g., temperature-regulated or light-regulated).

In some embodiments, the living cell contains a modified genome and a plasmid that facilitates expression of a T7 inhibitor, wherein the modified genome of the living cell comprises: (a) an integration of a polynucleic acid sequence encoding for and driving the expression of the non-naturally occurring nucleobase-editing fusion protein, wherein the sequence driving the expression of the fusion protein comprises a sequence bound by Lacl repressor that inhibits transcription of the fusion protein when Lacl is bound; and (b) a deletion of genomic sequence encoding for uracil deglycosylase. In some embodiments, the T7 inhibitor is T7 lysozyme. As used herein, the term“inhibits transcription” refers to a decrease in the expression of the non-naturally occurring nucleobase-editing fusion protein by about 5%, 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90%, or more than 95% relative to the level of expression in the absence of Lacl. Methods of measuring and comparing expression levels are known to those skilled in the art.

In some embodiments, the living cell is treated to increase the expression and/or activity of the uracil deglycosylase inhibitor, ugi (Savva R. and Pearl L.H., Nat. Struct. Biol. 1995 Sep; 2(9): 752-57). For example, in some embodiments, a plasmid encoding for an expressible uracil deglycosylase inhibitor is delivered to the living cell, and the expression of the uracil deglycosylase inhibitor is stimulated.

In some aspects, the invention relates to kits for performing targeted dynamic hypermutation. In some embodiments, the kit comprises: (a) a polypeptide comprising the amino acid sequence of a non-naturally occurring nucleobase-editing fusion protein comprising a processive polynucleic acid-binding protein fused to a nucleobase-editing enzyme; and (b) a polynucleic acid sequence comprising, from 5’ to 3’: a promoter region that is bound by the non-naturally occurring nucleobase-editing fusion protein of (a) in a sequence-specific manner; a cloning site; and a terminator region comprising a terminator array.

In other embodiments, the kit comprises: (a) a polynucleic acid sequence encoding for and driving the expression of a non-naturally occurring nucleobase-editing fusion protein comprising a processive polynucleic acid-binding protein fused to a nucleobase-editing enzyme; and (b) a polynucleic acid sequence comprising, from 5’ to 3’: a promoter region that is bound by the non-naturally occurring nucleobase-editing fusion protein of (a) in a sequence-specific manner; a cloning site; and a terminator region comprising a terminator array.

In some embodiments, at least one component in the kit is provided in a desiccated or lyophilized form. In other embodiments, at least one component of the kit is provided in a solubilized form. In some embodiments, the kit further comprises at least one buffer. In some embodiments at least one of the at least one buffers is a reaction buffer.

The term“cloning site,” as used herein refers to a segment of DNA that facilitates the cloning of a polynucleic acid comprising a target region. In some embodiments, the cloning site is a multiple cloning site comprising endonuclease restriction sites for restriction- mediated cloning. In some embodiments the cloning site is a TA cloning site. In some embodiments, the cloning site comprises a nucleic acid sequence that facilitates homologous recombination.

In some embodiments, the kit also comprises competent cells for use in the cloning of the target region. For example, in some embodiments, the competent cells are chosen from the list consisting of TOP10, OmniMax, PIR1, PIR2, INV a F, INV110, BL21, Machl, DHlOBac, DH10B, DH12S, DH5a, Stbl2, Stbl3, and Stbl4. XLl-Blue, XL2-Blue, and related strains.

EXAMPLES

Example 1: Implementation of Dynamic Targeted Hypermutation .

The implementation of dynamic target hypermutation (DTH) depends on the action of a polynucleic acid-binding protein fused to a nucleobase-editing enzyme, such as an RNA polymerase combined with a cytidine deaminase. To demonstrate the DTH methodology, RNA polymerase from a bacteriophage (T7) was fused to cytidine deaminase from Rattus norvegicus (rApobecl) to form various rApol-T7 constructs. These constructs specifically bind to a sequence of DNA called the T7 promoter, which is positioned adjacent to the target sequence of DNA (TABLE 1). Various constructs were engineered and tested in multiple reporter assays (TABLE 1 and TABLE 2).

When rApol-T7 initiates transcription at the promoter site, the DNA of the target sequence is exposed and altered by the action of the T7 RNA polymerase and altered by the rApol domain. Since the T7 polymerase of rApol-T7 is processive, it continues to travel along the DNA target sequence until it reaches a terminating sequence at the end of the DNA target sequence. Importantly, data disclosed herein demonstrate that rApol -T7 has a high mutation rate and low toxicity relative to global methods (mutagenic plasmid [MP6], which is the current gold standard for in vivo global mutagenesis methods).

Additional components can provide further constraints so that mutations are limited to a defined stretch of DNA (see Examples 2-4). These constraints (and their underlying importance to the implementation of DTH) have not been demonstrated previously.

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TABLE 1: List of constructs tested with accompanying expectations and observations. ro

TABLE 2: List of assays used to test rApol-T7 constructs. Example 2: Decreasing Mutagenesis Downstream of the Target DNA.

Targeted mutagenesis is defined as the constraint of mutations to a defined stretch of DNA. In other words, mutations should not appear outside of the target region. In the implementation of rApol-T7 demonstrated in Example 1, one might expect that the mutation frequency upstream of the T7 promoter would be very low. However, preventing mutations downstream of the target region could be a tremendous challenge. Previous data has shown that monomeric RNA polymerases can be quite processive and carry out transcription for exceptionally long stretches of DNA - in excess of 20kb in the case of T7 RNA polymerase (Rong et al., J. Biol. Chem. 1998 Apr 24; 273(17): 10253-60; Thiel et al., J. Gen. Virol. 2001 Jun; 82(Pt 6): 1273-81). Effective termination of transcription is further complicated by the context-dependent nature of termination efficiency (Mairhofer et al., ACS Synth. Biol. 2015 Mar 20; 4(3): 265-73).

An unsuccessful termination event for rApol-T7 can result in the incorporation of undesired mutations throughout many kilobases of DNA downstream of the target region. These undesired mutations are typically catastrophic in the context of directed evolution, as these changes can produce numerous variants outside of the gene of interest that overcome a selection scheme in a living organism (i.e.,“cheaters”). Previous attempts at technologies similar to DTH have failed to address or entirely ignored undesired mutagenesis downstream of the target region or elsewhere in the genome. Therefore, experiments were designed to test the possibility of off-target mutagenesis, and if necessary eliminate it.

A start codon reversion drug resistance assay was designed in which two drug resistance genes were positioned in series, both of which lacked a start codon (FIG. 4A). When only filler DNA (no T7 UUCG terminator) separated the two drug resistance genes, there was minimal termination of rApol-T7. Indeed, similar frequencies of start codon reversion were observed for both drug resistance genes (FIGs. 4B). Inserting a single terminator between the drug resistance genes resulted in only a minor reduction in the frequency of start codon reversion in the downstream gene compared to upstream gene (FIGs. 4B). Likewise, inclusion of 2 or 3 common terminators decreased, but did not prevent off- target mutagenesis carried out by rApol-T7 (FIGs. 4B). Indeed, use of 1 to 3 common terminators common for T7 in DTH results in mutagenesis for a long distance downstream of the target DNA. Subsequent engineering of larger terminator arrays (up to 10 copies) further reduced the mutagenesis frequency in downstream genes to background levels while still accumulating mutations in gene upstream of the terminator array (FIGs. 4B).

Additional experiments were performed using LacO operons recruiting the Lac repressor to interfere with T7 processivity and promote termination; however, these limited attempts were unsuccessful.

Example 3: Minimal Expression of rApol-T7.

Similar to termination, it was found that expression levels of rApol-T7 can result in untargeted mutagenesis if left unchecked. In preliminary implementations of the DTH using rApol-T7, significant cytotoxicity was observed even when rApol-T7 was expressed under limiting conditions through a common promoter (such as an arabinose inducible promoter with glucose suppression). In the context of directed evolution, such widespread changes results in the regular appearance of“cheaters.”

Thus, experiments were designed to limit the expression of rApol-T7 by alternative strategies beyond traditional promoters. In the most successful implementation, the combined effects of reducing promoter strength (TABLE 3; Registry of Standard Biological Parts, parts.igem.org/Promoters/Catalog/Anderson; Camsund et al., J. Biol. Eng. 2014 Jan 27; 8(1): 4) and limiting copy number of the rApo-T7 gene were critical for limiting cytotoxicity when utilizing rApol-T7 in E. coli. Expression of rApol-T7 constructs under medium copy number conditions was highly toxic. Moreover, use of split T7 to increase mutagenesis and reduce toxicity failed because T7 polymerase activity of the split constructs was unacceptably low.

TABLE 3: List of potential promoter sequences for driving the expression

of a nucleobase-editing fusion protein and their accompanying strengths.

The unbolded nucleotides are part of the consensus promoter sequence

(BBa_J23l l9) among all promoters while the bold nucleotides highlight

the differences between the individual promoters and the consensus

sequence.

TABLE 4: List of potential promoter sequences that can be bound by

nucleobase-editing fusion proteins.

Example 4: Inducible Expression of rApol-T7.

No previously described mutagenesis methodology has demonstrated conditional control that allows users to conveniently turn on and shut off targeted mutation accumulation in a living organism. While MP6 inducible system have been disclosed (Badran A.H. and Liu D.R., Nat. Commun. 2015 Oct 7; 6: 8425), it carries out mutagenesis globally.

Commonly used non-inducible mutagenesis methods used in living organisms are designed to continuously carry out global mutagenesis, which forces users to isolate the final libraries of evolved genes of interest from mutagenic organisms and subsequently transfer these libraries to a non-mutagenic organism for downstream sequencing and characterization. Conditional control of mutagenesis would allow users to switch off targeted mutagenesis after a desired portion of time, effectively eliminating the need to isolate and transfer evolved libraries from one organism to another.

The results disclosed herein demonstrate that the activity of rApo-T7 can be conditionally tuned by chemically inducing the expression of Lacl-repressed rApol-T7 with IPTG, such that higher expression levels of T7 polymerase correlate with increased levels of mutagenesis (FIG. 11A-11B). Optimization of conditional promoter strength and copy number was required to avoid uninduced mutagenesis and cellular toxicity. For example, expression under full-strength conditional promoters showed leaky expression when uninduced and toxicity when induced. Likewise, reducing promoter strength failed to address leaky expression and lack of induction when expressing from a medium copy plasmid. By further tuning the expression of T7 lysozyme— a T7 inhibitor— relative to T7 RNA polymerase and optimizing the interaction between both partners, it is likely that mutagenesis levels under repressive conditions will fall to background levels. Example 5: Materials and Methods for Examples 6 and 7.

General Methods : All PCR reactions for restriction cloning and recombineering targeting cassettes were performed using Q5 High Fidelity DNA Polymerase (New England Biolabs). Primers were ordered from Life Technologies and g-blocks were ordered from Integrated DNA Technologies.

Chemicals. Kanamycin monosulfate was purchased as a solid from Alfa Aesar (J61272). Tetracycline hydrochloride was purchased as a solid from Calbiochem (58346). Fosfomycin was purchased as a solid from Alfa Aesar (J6602). Rifampicin was purchased as a solid from TCI (R0079). Ampicillin was purchased as a solid sodium salt form Fisher bioreagents (BP1761-25). Streptomycin sulfate was purchased as a solid from MP

Biomedicals (100556). Chloramphenicol was purchased as a solid from Alfa Aesar

(B20841). Tetrazolium chloride was purchased as a solid from Aldrich (T8877). L-rhamnose was purchased as a solid from Sigma- Aldrich (W373011). L-arabinose was purchased as a solid form Chem Impex (01654). Isopropyl b-D-l-thiogalactopyranoside (IPTG) was purchased as a solid from Sigma-Aldrich (I6758-1G). Antifoam 204 was purchased as liquid from Sigma (A8311-50ML). LB was purchased as a solid form Difco (244620). Agar was purchased as a solid from Alfa Aesar (A10752). Cycloheximide was purchased as a solid from Chem Impex (00083). Ethylmethanesulfonate (EMS) was purchased from Sigma Aldrich (M0880-1G).

Cloning: All plasmids were generated by restriction cloning. Ligation reactions were performed using Quick Ligase (New England Biolabs). All DNA cloning was performed in DH10B cells (Invitrogen). The rApol gene was amplified from pET28b-BEl (Komor et ah, Nature. 2016 May 19; 533(7603): 420-24) and the T7 RNA polymerase gene was amplified from pTara (Wycuff D. R. and Matthews K. S., Anal. Biochem. 2000 Jan 1; 277(1): 67-73). Mutation assay reporter plasmids utilize the single-copy BAC origin and the terminator arrays of the UETCG-T7 derivative of the T7 terminator (Mairhofer et ah, ACS Synth. Biol. 2015 Mar 20; 4(3): 265-73), were generated by serial insertion of the annealed oligos Nhel- UUCG-BamHI S and Nhel-UUCG-BamHI AS.

TABLE 5. Strain table. The genotypes of strains used in this work are shown. The“xoy” notation indicates a replacement of“x” with“y” through lambda red recombineering.

TABLE 6. Primer table. This table shows the primers used for lamda red

recombineering, restriction cloning of the terminator arrays, colony PCR

and Sanger sequencing.

General recombineering : The E. coli genome was edited using seamless lambda red recombineering with ccdB counterselection as previously described (Wang et al., Nucleic Acids Res. 2014 Mar; 42(5): e37). Cells were first transformed with the temperature- sensitive psclOl-gbaA recombineering plasmid and plated on LB agar with 10 mg/mL tetracycline and incubated for 24hr at 30°C. Colonies were picked and grown in LB with 10 mg/mL tetracycline overnight at 30°C (l8-2lhrs). The overnights were diluted 25-fold in LB with 10 mg/mL tetracycline and grown at 30°C for about 2 hours until they reached an ODeoo of 0.3-0.4. The ccdA antitoxin and recombineering machinery were then induced by adding arabinose and rhamnose to a final concentration of 2 mg/mL each and then growing the cultures at 37°C for 40 minutes to an ODeoo of -0.6. The cultures were then placed on ice, washed twice with ice-cold sterile ddH ₂ 0, resuspended in -25 pL of ice-cold sterile ddtbO and electroporated with -200 ng of the appropriate kan-ccdB targeting cassette (L8kV, 5.8ms, 0.1 cm cuvette, BioRad Micropulser). The cells were then recovered in SOC with 2mg/mL arabinose at 30C for 2 hours, then plated on LB agar plates with 50 mg/mL kanamycin and 2 mg/mL arabinose and incubated for 24 hours at 30°C. Colonies that appeared had incorporated the kan-ccdB targeting and were picked and grown in LB with 50 mg/mL kanamycin and 2 mg/mL arabinose at 30°C overnight (18-21 hours). The cultures were then diluted 25-fold in LB with 50 mg/mL kanamycin and 2 mg/mL arabinose and grown at 30°C for about 2 hours until they reached an ODeoo of 0.3-0.4. The recombineering machinery was then induced by adding rhamnose to a final concentration of 2 mg/mL each and then growing the cultures at 37°C for 40 minutes to an ODeoo of -0.6. The cultures were then placed on ice, washed twice with ice-cold sterile ddtbO, resuspended in -25 pL of ice- cold sterile ddtbO and electroporated with -200 ng of the final targeting cassette that will replace the kan-ccdB cassette currently integrated in the genome (L8kV, 5.8ms, O.lcm cuvette, BioRad Micropulser). The cells were then recovered in SOC with 2 mg/mL arabinose at 30C for 2 hours, then were washed once with LB to remove the arabinose and cease production of the ccdA antitoxin. The cultures were then plated on LB agar plates at various dilutions with 100 mg/mL streptomycin and incubated for 24 hours at 37°C. Without the ccdA antitoxin, the ccdB toxin will kill cells that have not replaced the integrated kan ccdB cassette with the final targeting cassette. The colonies that grow should have the final targeting cassette integrated, but were screened by PCR or sequencing to confirm final targeting cassette integration as some colonies simply have inactivated the ccdB toxin. Once a clone with the desired change was found, the temperature- sensitive psclOl-gbaA

recombineering plasmid was cured by plating on LB agar with 100 mg/mL streptomycin and incubating at 42°C for 18-21 hours, then streaking a colony from the plate on LB agar with 100 mg/mL streptomycin and incubating at 42°C for another 18-21 hours. The colonies from the second plate were grown in LB with 100 mg/mL streptomycin at 37°C to be used or to make glycerol stocks. The colonies were also incubated in LB with 10 mg/mL tetracycline at 30°C to ensure tetracycline sensitivity and confirm that the recombineering plasmid was cured. ung Deletion: In order to prevent dU dC repair and increase the mutagenesis rate, uracil DNA glycosylase {ung) was deleted in several of the strains used in this work (Duncan B.K., J. Bacteriol. 1985 Nov; 164(2): 689-95). Deletion of ung was accomplished through lambda red recombineering, using a kan-ccdB targeting cassette that was amplified from R6K-kan-ccdB using primers 5’ Ung kanccdB and 3’ Ung kanccdB. Once the kan-ccdB targeting cassette replaced the ung gene, the kan-ccdB cassette was deleted using the annealed oligos delUng S and delUng AS as the targeting cassette to generate a markerless ung deletion.

Increasing lad expression: The expression of the la repressor in DH10B cells was increased by replacing the endogenous Pi _aci promoter with the strong Ptac promoter using lambda red recombineering. A kan-ccdB targeting cassette was amplified from R6K-kan- ccdB using primers 5’ pLacI::kanccdB and 3’ pLacI::kanccdB and used to replace the endogenous Pi _aci promoter with the kan-ccdB cassette. The kan-ccdB cassette was replaced with P _tac using the annealed oligos pLacI::pTac S and pLacI::pTac AS.

Deleting the motAB and csgABCDEFG operons to decrease biofilm formation:

Deletions of the motAB operon (Pratt L.A. and Kolter R., Mol. Microbiol. 1998 Oct; 30(2): 285-93) and the csgABCDEFG (Prigent-Combaret et ah, Environ. Microbiol. 2000 Aug; 2(4): 450-64) have been shown to produce strains of E. coli that are deficient in biofilm formation. To minimize inlet line contamination and clogs in bioreactor experiments due to biofilms, the motAB and csgABCDEFG operons were deleted using one-step DIRex lambda red recombineering (Nasvall J., PLoS One. 2017 Aug 30; 12(8): e0l84l26). The motAB targeting half-cassettes were amplified from R6K-AmilCP-kan-ccdB using primers delmotDF and AmilCP-KanR and from R6K-kan-ccdB-AmilCP using primers delmotDR and KanF- AmilCP. The csgABCDEFG targeting half-cassettes were amplified from R6K-AmilCP-kan- ccdB using primers delcsgDF and AmilCP-KanR and from R6K-kan-ccdB-AmilCP using primers delcsgDR and KanF-AmilCP. The motAB or csgABCDEFG half cassettes were co electroporated to replace motAB or csgABCDEFG with a kan-ccdB cassette flanked by large AmilCP inverted repeats nested between short 30bp direct repeats. The repeat architecture leads to a high rate of spontaneous excision that was selected for using ccdB counterselection to obtain markerless deletions of motAB and csgABCDEFG.

Deactivated rApol : The E63Q mutant of rApol cytidine deaminase has been shown to be catalytically dead (Navaratnam et ah, Cell. 1995 Apr 21; 81(2): 187-95). Lambda red recombineering was used to generate strains with deactivated rApol and deactivated rApoI- T7 using a kan-ccdB targeting cassette that was amplified from R6K-kan-ccdB using primers 5’ drApoI::kanccdB and 3’ drApoI::kanccdB. Once the kan-ccdB targeting cassette replaced the E63 codon, the kan-ccdB cassette was replaced with a glutamine codon using the annealed drApol S and drApol AS as the targeting cassette to generate an E63Q mutant.

Insertion of rApol and MutaT7 into the E. coli genome: rApol and MutaT7 were inserted into the genome at the seam of the large A(araA-leu)7 ^' 691 deletion in DH10B E. coli using lambda red recombineering. A kan-ccdB targeting cassette was amplified from R6K- kan-ccdB using primers dAraLeu7697 kanccdB F and dAraLeu7697 kanccdB R and used to the insert the kan-ccdB cassette between 62,378 bp and 62,379 bp in the DH10B genome (Durfee et ah, J. Bacteriol. 2008 Apr; 190(7): 2597-606). Then targeting cassettes containing rApol or MutaT7 were amplified from BBa_J23l l4_lacO rApol and BBa_J23l l4_lacO MutaT7, respectively, using primers dAraLeu7697-rApoI and dAraLeu7697-T7 and were used to replace kan-ccdB with rApol or MutaT7.

Replacement of promoter BBa_J23114 with PAiiaco-Tenth' The BBa_J23l l4 promoter from the Anderson Collection (parts.igem.org/Promoters/Catalog/Anderson) that controlled the expression of rApol or MutaT7 from the DH10B genome was replaced with the promoter PAiiaco-Tenth which was intended to be a weaker version of the PAiiaco promoter (Camsund et ah, J. Biol. Eng. 2014 Jan 27; 8(1): 4). A kan-ccdB targeting cassette was amplified from R6K-kan-ccdB using primers 5' prApoI::kanccdB and 3' prApoI::kanccdB and used to replace BBa_J23114 with a kan-ccdB cassette. The kan-ccdB cassette was replaced with PAiiaco-Tenth using the targeting cassette amplified from the pAllacO-tenth gblock using primers PAllacO-l F and PAllacO-l R.

Mutation assay : To test mutagenesis rates, the control and mutagenic strains (Strep ^R ) carrying reporter plasmids (Amp ^R ) were streaked out on LB agar with 100 mg/mL

streptomycin and 100 mg/mL ampicillin and grown at 37°C for 24 hours. Then single colonies were picked in triplicate for each sample and grown in 5mL LB with 100 mg/mL streptomycin, 100 mg/mL ampicillin and 25mM arabinose (with 10 mg/mL chloramphenicol if the strain contains MP6) at 37°C, 250 r.p.m. for 24 hours. Then 1 mL aliquots of each overnight were pelleted at 6000 Xg for 3 minutes and resuspended in 1 mL LB to remove arabinose. Then 50 pL of each resuspension was plated on LB agar plates with 50 mg/mL tetrazolium chloride and 200 mg/mL kanamycin, 20 mg/mL tetracycline, 100 mg/mL fosfomycin or 100 mg/mL rifampicin unless otherwise stated. 50 pL of a 100, 000-fold dilution of each culture was also plated on LB agar with 100 mg/mL streptomycin, 100 mg/mL ampicillin and 50 mg/mL tetrazolium chloride. After incubating the plates at 37°C for 48 hours, they were imaged by inverting the plates onto transparencies and scanning on a document scanner at a resolution of 400 d.p.i. The colonies were then counted using the software OpenCFU (3.9.0) (Geissmann Q., PLoS One. 2013; 8(2): e54072), with minimum colony radius set to 3, the maximum colony radius set to 50 and the regular threshold set to 4.

Chemical mutagens : Mutagenesis with ethane methyl sulfonate (EMS) was performed as previously described (Cupples C.G. and Miller J.H., Proc. Natl. Acad. Sci. U.S.A. 1989 Jul; 86(14): 5345-49). An overnight culture of each sample was subcultured and grown until it reached a density of 2-3 X 10 ⁸ cells per mL (log phase). 5 mL aliquots of cells were chilled on ice, washed twice with sodium phosphate buffer (pH 7) and resuspended in 1 mL of lx PBS in a 1.5 mL eppendorf tube. EMS was added while cold by pipetting 14 pL of EMS into 1 ml of resuspended cells. Eppendorfs were sealed, and mixed at 1000 r.p.m. for 60 minutes at 37°C. The cells were then washed twice with LB, and resuspended in 1 mL of LB.

Immediately after washing, a viability measurement was performed by plating 50 pL of a 10,000-fold dilution of mutagen and mock- treated cultures on LB agar with 100 pg/mL streptomycin, 100 pg/mL ampicillin and 50 pg/mL tetrazolium chloride. For mutation rate assessment, 500 pL of each resuspension were inoculated into 5 ml of LB with 100 pg/mL streptomycin and 100 pg/mL ampicillin. The cultures were grown at 37°C for 20 hours, then 50 pL of each culture was plated on LB agar 50 pg/mL tetrazolium chloride and 100 pg/mL rifampicin. 50 pL of a 100,000-fold dilution of each culture was also plated on LB agar with 100 pg/mL streptomycin, 100 pg/mL ampicillin and 50 pg/mL tetrazolium chloride. After 48 hours of incubation, plates were imaged on a document scanner at a resolution of 400 d.p.i, and colonies were subsequently counted using the software OpenCFU (3.9.0)

(Geissmann Q., PLoS One. 2013; 8(2): e54072), with minimum colony radius set to 3, the maximum colony radius set to 50 and the regular threshold set to 4.

Continuous culture of T7 promoter + antisense T7 promoter reporter plasmid and sequencing : The T7 promoter + antisense T7 promoter reporter plasmid was continuously cultured in the MutaT7-c.¾' ⁺ mot strain in a 70 mL culture in a round-bottomed flask that was slowly stirred in a 37°C mineral oil bath. The culture was aerated through a needle that was connected to a standard aquarium pump and LB with 100 pg/mL streptomycin, 100 pg/mL ampicillin and 0.5% isopropanol (as antifoaming agent) was fed into the culture via a needle connected to a peristaltic pump at a rate of -0.5 volumes/hour. Fractions were collected every 3 days for 12 days. Each fraction was plated for single colonies on LB agar with 100 pg/mL ampicillin and 10 clones from each fraction were Sanger sequenced by colony PCR with primers 1493 and 1494.

Continuous culture of T7 promoter + filler DNA and T7 promoter + terminators reporter plasmids and sequencing : The T7 promoter + filler DNA and T7 promoter + terminators reporter plasmids were continuously cultured in the Aung (negative control), MutaT7 and MP6 strains in 20 mL cultures in a previously described multiplex bioreactor setup (Miller et ah, J. Vis. Exp. 2013 Feb 23; (72): e50262). The reactor was stored in a 37°C warm room and was aerated and stirred with aquarium pumps. LB with 100 pg/mL streptomycin, 100 pg/mL ampicillin, 100 pg/mL cycloheximide, 0.01% (v/v) antifoam 204 and 150 mg/mL arabinose (+10 mg/mL chloramphenicol in the case of the MP6 strain) was pumped into each reaction vessel at a rate of 0.87 volumes/hour. Fractions were collected every 3 days. Each fraction was plated on LB agar with 100 mg/mL streptomycin and 100 mg/mL ampicillin and 12 single colonies from each plate were grown in 5 mL LB with 100 mg/mL ampicillin. DNA was isolated from each overnight using the Qiaprep 96 Turbo Miniprep Kit and quantified using PicoGreen assay. 1 ng of each sample was prepared using the Illumina NexteraXT Sample Preparation kit. Samples were barcoded and pooled prior to sequencing on an Illumina MiSeq 300v2 cartridge to obtain 2 x 150 base pair paired-end reads. Sequencing reads were aligned against respective plasmid sequences using bwa mem 0.7.l0-r789 [RRID:SCR_0l09l0]. Allele pileups were generated using samtools v.0.1.19 mpileup [RRID:SCR_002l05] with flags -d 10000000— excl-flags 2052, and allele counts/frequencies were extracted (Li H., Bioinformatics. 2011 Nov 1; 27(21): 2987-93; Li et al., Bioinformatics. 2009 Aug 15; 25(16): 2078-79). Only positions with greater than lO-fold coverage in all replicates of each sample were included in the analysis. Fixed variant alleles (present at greater than 85% frequency) for each sample are reported. Sanger sequencing was also performed on a PCR amplicon from 96 clones of Aung (negative control) and MutaT7 after 15 days of continuous culture carrying T7 promoter + terminators reporter plasmid. Primers 2165 and 1197 were used to amplify and Sanger sequence the Kan ^R gene.

Example 6: Directed Mutagenesis.

Monomeric RNA polymerases possess inherently high promoter specificity (Rong et al., J. Biol. Chem. 1998 Apr 24; 273(17): 10253-60) and high processivity during

transcription (Thiel et al., J. Gen. Virol. 2001 Jun; 82(6): 1273-81). Cytidine deaminases are potent DNA-damaging enzymes that act on ssDNA substrates formed during transcription (Thiel et al., J. Gen. Virol. 2001 Jun; 82(6): 1273-81; Ramiro et al., Nat. Immunol. 2003 May; 4(5): 452-56). It was envisioned that merging the unique features of these two enzyme classes by creating a fusion“mutaT7” protein consisting of a cytidine deaminase (rApol) fused to T7 RNA polymerase (T7-pol) would facilitate the targeting of mutations to any DNA region lying downstream of a T7 promoter (FIG. 1B). Thus, rApol was fused to the N- terminus of T7-pol because the carboxy group of the T7-pol C-terminus is implicated in catalysis during the elongation phase (Lykke- Andersen J. and Christiansen J., Nucleic Acids Res. 1998 Dec 15; 26(24): 5630-35). As preliminary overexpression appeared to be toxic, reduced expression of mutaT7 was sought by reducing promoter strength and subsequently minimizing copy number via integration into the E. coli genome with seamless recombineering (FIG. 9, TABLE 5, and TABLE 6). Targeted mutagenesis was assayed using a codon reversion assay based on bacteria artificial chromosome reporter plasmids either having or lacking a T7 promoter sequence upstream of silent drug resistance genes with ACG triplets in place of their ATG start codons (FIG. 1C, FIG. 5, FIG. 6, and FIG. 8). The kanamycin (Kan) resistance gene Kan ^R was placed immediately downstream of the T7 promoter. In this assay, successful C~^T mutagenesis at the start codon yields Kan-resistant colonies. Global mutagens such as MP6 yielded high levels of Kan-resistant colonies regardless of the presence or absence of a T7 promoter, consistent with a lack of targeting. In contrast, significant Kan resistance was only observed in mutaT7 strains with reporter plasmids having a T7 promoter upstream of the Kan ^R gene, indicating successful targeted mutagenesis. Importantly, expression of a catalytically dead version of mutaT7 (drApol-T7) lacking a critical residue for cytidine deaminase activity (Harris et ah, Mol. Cell. 2002 Nov; 10(5): 1247-53) yielded Kan resistance frequencies similar to background levels, indicating that T7 activity was not responsible for increased Kan resistance (FIGs. 10A-10C).

T7 promoter-dependent Kan ^R mutagenesis by mutaT7 shows that one can target mutagenesis to a desired DNA region. Since T7-pol is highly processive, it was anticipated mutations would also be introduced further downstream of the T7 promoter. The presence in the reporter plasmid of a tetracycline -resistance (Tel ^R ) gene with an inactive, ACG start codon separated by an -1.6 kbp spacer DNA from the Kan ^R gene provided a mechanism to assay such processivity. High levels of mu taT7 -dependent Tet resistance was observed only in reporter strains having the T7 promoter, consistent with targeting and processive introduction of mutations across a lengthy DNA region. Once again, global mutagens generated Tet-resistant colonies in all reporter plasmids.

Targeted mutagenesis using the processive mutaT7 chimera requires not just recruitment to a DNA locus but also termination upon reaching the end of the DNA region of interest. To address termination, Kan^Te^ reporter plasmids were used in which the DNA spacer was replaced with one or more T7 terminators and then assayed for both Kan and Tet resistance. Four or more copies of the T7 terminator was sufficient to prevent mutagenesis beyond the DNA of interest (FIGs. 4A-4B). Using the T7 terminator array, Tet resistance was observed for mutaT7 strains similar to background levels, while Kan resistance remained high. Global mutagens again induced high levels of Kan- and Tet-resistance, regardless of the presence of a T7 terminator array (TABLE 7). To further assess whether the MutaT7 chimera induces mutagenesis only on the target DNA of interest, the emergence of bacterial colonies resistant to rifampicin was evaluated (Garibyan et ah, DNA Repair. 2003 May; 2(5): 593-8) and fosfomycin (Nilsson A.I., Antimicrob. Agents Chemother. 2003 Sep; 47(9): 2850- 58). Because resistance to these two drugs can emerge by multiple mutations in the genome, the appearance of resistant colonies correlates with off-target mutation rates in the genome (Badran A.H. and Liu D.R., Curr. Opin. Chem. Biol. 2015 Feb; 24: 1-10; Garibyan et al., DNA Repair. 2003 May; 2(5): 593-8), in analogy to the emergence of“cheaters” in directed evolution schemes. Growth of E. coli on either rifampicin- or fosfomycin-treated plates revealed that mutaT7-expressing samples displayed drug resistance frequencies comparable to background levels, as opposed to the high frequencies of antibiotic resistance which appeared in all global mutagenesis samples (FIG. 1E and FIGs. 7A-7D).

An important advantage of targeted mutagenesis is the ability to attain much larger viable library sizes by avoiding off-target, toxic mutations in essential genes outside the DNA region of interest. Based on the apparently low off-target mutagenesis rate of mutaT7, one might expect that E. coli carrying mutaT7 would have significantly higher viability than bacteria treated with global mutagens. Indeed, consistent with prior work (Badran A.H. and Liu D.R., Curr. Opin. Chem. Biol. 2015 Feb; 24: 1-10), very low viability was observed in all populations treated with global mutagens, whereas populations expressing mutaT7 possessed viability similar to untreated cells (FIG. 1F). It was also found that the total number of Kan- resistant colonies was similar between mutaT7 and globally mutagenized samples (FIG. 1G) despite the relatively lower mutagenesis rate (FIG. 1C), highlighting the beneficial effect that minimizing off-target mutations has on library size for in vivo evolution schemes.

TABLE 7. Mutation assay data. This table shows the antibiotic resistant

CFU/mL and frequencies obtained in the mutation assay.

Example 7: Characterization of On-Target Versus Off-Target Mutagenesis.

The assays in FIGs. 1A-1G show that mutaT7 targets mutations specifically to genes downstream of a T7 promoter and that the region of mutagenesis can be constrained by a terminator array. DNA sequencing was then used to better understand the processivity of mutagenesis and the extent of on-target versus off-target mutagenesis. An E. coli population expressing mutaT7 and an episomally expressed Kan ^K /Tel ^K reporter plasmid was allowed to drift in the absence of selection pressure for 15 days followed by Sanger sequencing of the Kan ^R gene. Consistent with the expected processivity of mutaT7, mutations were found at multiple sites across the entire span of the Kan ^R target gene independent of selection pressure (FIG. 2A).

Next, next generation sequencing was performed of the entire episomal reporter plasmid DNA sequence of 36 clones drawn from the same E. coli population as in FIG. 2A to directly assess on-target versus off-target mutagenesis across a -10 kb stretch of DNA containing only ~l kb of intended target DNA. The same approach was used to assess mutagenesis in a control E. coli population not treated with any mutagen and a population subjected to global mutagenesis. The clones drawn from mutaT7 samples displayed many more mutations throughout the plasmid when the terminator array was removed but the T7 promoter was maintained (FIG. 2B). Treatment with the MP6 global mutagen also led to mutations across the entire episome. In contrast, off-target mutations in mutaT7 samples appeared almost exclusively within the Kan ^R target gene when both a promoter and terminator array were present, even after 15 days of continuous culturing, with off-target mutations present only to the same extent as in the control sample not treated with any mutagen. Additionally, the number of mutations in the target gene across different clones increases in frequency and position as cultures continuously grow without selection pressure (FIG. 2C). This observation suggests that, in contrast to the use of other genetic methods for global mutagenesis where the organism generally identifies a mechanism to shutdown mutagen expression, the high on-target to off-target mutation ration of mutaT7 is enabling long-term maintenance of expression in cells.

One disadvantage of mutaT7 is its limited mutational spectrum consistent with the use of a cytidine deaminase as the mutagenic component. Indeed, the sequencing results described above indicate that C to T transitions are exclusively obtained in the sense strand of targeted DNA using a single T7 promoter. It was hypothesized that the mutational spectrum could be doubled by installing a second T7 promoter that would recruit mutaT7 to the 3 '-end of the DNA of interest. Installation of an antisense T7 promoter leads to the appearance of both G to A and C to T transitions throughout the target gene (FIG. 2D).

In summary, the processively acting mutaT7 chimera is capable of selectively targeting mutations to large, yet well-defined, regions of DNA in a living system with minimal human intervention. Moreover, the availability of T7 variants with altered transcription rates (Bonner et al., J. Biol. Chem. 1994 Oct 7; 269(40): 25120-28) likely provides the opportunity to fine-tune mutation rates. Utilizing other base editing enzymes in place of cytidine deaminase, such as the adenosine deaminases (Gaudelli et ah, Nature. 2017 Nov 23; 551(7681): 464-71), can significantly widen the mutational spectrum of mutaT7 and further enable the creation of rich, diverse DNA libraries in vivo with minimal off-target effects. The ubiquitous applicability and high specificity of T7 RNA polymerase in a large number of diverse organisms (Lieber et ah, Eur. J. Biochem., 1998 Oct 1; 217(1): 387-94) will enable implementation of targeted mutagenesis in a broad range of evolutionary and synthetic biology settings.

Example 8: Materials and Methods for Examples 9-12.

General·. All PCR reactions for restriction cloning and recombineering targeting cassettes were performed using Q5 High Fidelity DNA Polymerase (New England Biolabs). All colony PCR reactions for sequencing were performed using OneTaq Quick- Load 2x Master Mix with Standard Buffer (New England Biolabs). Primers were obtained from Life Technologies. Gene blocks were obtained from Integrated DNA Technologies.

Reagents: The following reagents were obtained as indicated: Kanamycin

monosulfate, fosfomycin, agar, and chloramphenicol (Alfa Aesar J61272, J66602, A10752, and B20841, respectively); tetracycline hydrochloride (CalBioChem 58346); rifampicin (TCI R0079); ampicillin (Fisher Bioreagents BP1760-25); streptomycin sulfate (MP Biomedical 100556); tetrazolium chloride, L-rhamnose, antifoam- 204, and ethyl methanesulfonate (Sigma-Aldrich T8877, W373011, A8311, and M0880, respectively); L-arabinose and cycloheximide (Chem-Impex 01654 and 00083, respectively); and lysogeny broth (LB; Difco 244620); anhydrous sodium phosphate dibasic and monobasic sodium phosphate

(Mallinckrodt 7917 and 7892, respectively); potassium chloride and isopropyl b-D-l- thiogalactopyranoside (Sigma P9333 and 16758, respectively); magnesium sulfate (Macron 6070-12); o-Nitrophenyl-P-galactoside and egg-white lysozyme (VWR 0789 and 0663, respectively); PopCulture lysis reagent (EMD Millipore 71092-4); 2-mercaptoethanol (Bio- Rad 161-0710); trimethoprim (Matrix Scientific 058373).

Cloning and Recombineering: All plasmids were generated by restriction cloning. Ligation reactions were performed using Quick Ligase (New England Biolabs). All DNA cloning was performed in DH10B cells (Invitrogen). The rApol gene was amplified from pET28b-BEl (Komer et ah, Nature. 2016 May 19; 533(7603): 420-2) and the T7 RNA polymerase gene was amplified from pTara (Wycuff and Matthews, Anal. Biochem. 2000 Jan 1; 277(1): 67-73). Mutation assay reporter plasmids utilizing the single-copy BAC origin and the terminator arrays of the UUCG-T7 derivative of the T7 terminator (Mairhofer et ah, ACS Synth. Biol. 2015 Mar 20; 4(3): 265-73) were generated by serial insertion of the annealed oligos Nhel-UUCG-BamHI S and Nhel-UUCG-BamHI AS (TABLE 10). Th e/oZA gene was amplified from DH10B genomic DNA. All E. coli strains used in this work were engineered using lambda red recombineering strategies described in detail below.

Mutation Assay: To assess mutagenesis rates, the control (Aung, rApol, drApol, and drApol-T7; TABLE 8) and mutagenic strains (MutaT7 and MP6; TABLE 8) (Strep ^R ) carrying reporter plasmids (AmpR) were streaked on LB agar with 100 pg/mL streptomycin and 100 pg/mL ampicillin and grown at 37 °C for 24 h in order to obtain clones. Single colonies were picked in triplicate for each sample and used to inoculate 5 mL LB with 100 pg/mL streptomycin, 100 pg/mL ampicillin, and 25 mM arabinose (with 10 pg/mL

chloramphenicol for the MP6 strain, TABLE 8), then shaken at 250 r.p.m. and 37 °C for 24 h to accumulate mutations during growth. 1 mL aliquots of each culture were pelleted at 6000 x g for 3 min and resuspended in 1 mL LB to remove arabinose. Each resuspension was plated on LB agar plates with 50 pg/mL tetrazolium chloride (a metabolic contrast dye for visualizing colonies) and the antibiotics indicated below to analyze mutation rates and viability:

• 50 pL of a 100, 000-fold dilution of each resuspension was plated on LB agar with 100 pg/mL streptomycin, 100 pg/mL ampicillin, and 50 pg/mL tetrazolium chloride. For samples from the MP6 strain, owing to lower growth of that strain, 50 pL of a 10, 000-fold dilution of each resus-pension was plated to obtain a more accurate count. The colony counts from these plates were used to calculate the cell viability (i.e., the number of live, ampicillin resistant cells) in CFU/mL for each sample (FIG. 13D).

• 50 pL of each resuspension was plated on LB agar plates with 200 pg/mL kanamycin and 50 pg/mL tetrazolium chloride. The colony counts from these plates were used to calculate the number of kanamycin resistant mutants in CFU/mL for each sample (FIG. 13E). The number of kanamycin resistant mutants in CFU/mL was divided by the number of live ampicillin resistant cells in CFU/mL for each sample to obtain the kanamycin resistant mutation frequency (FIG. 13B).

• 50 pL of each resuspension was plated on LB agar plates with 20 pg/mL tetracycline and 50 pg/mL tetrazolium chloride. The colony counts from these plates were used to calculate the number of tetracycline resistant mutants in CFU/mL for each sample. The number of tetracycline resistant mutants in CFU/mL was divided by the number of live ampicillin resistant cells in CFU/mL for each sample to obtain the tetracycline resistant mutation frequency (FIG. 13B).

• 50 pL of each resuspension was plated on LB agar plates with 100 pg/mL rifampicin and 50 pg/mL tetrazolium chloride. The colony counts from these plates were used to calculate the number of rifampicin resistant mutants in CFU/mL for each sample. The number of rifampicin resistant mutants in CFU/mL was divided by the number of live ampicillin resistant cells in CFU/mL for each sample to obtain the rifampicin resistant mutation frequency (FIG. 13C).

• 50 pL of each resuspension was plated on LB agar plates with 100 pg/mL fosfomycin and 50 pg/mL tetrazolium chloride. The colony counts from these plates were used to calculate the number of fosfomycin resistant mutants in CFU/mL for each sample.

The number of fosfomycin resistant mutants in CFU/mL was divided by the number of live ampicillin resistant cells in CFU/mL for each sample to obtain the rifampicin resistant mutation frequency (FIG. 19C).

Plates were incubated at 37 °C for 48 h, then imaged by inverting the plates onto transparencies and scanning on a document scanner at a resolution of 400 dots per inch (d.p.L). The colonies were then counted using the software OpenCFU (3.9.0) (Geissmann, PLoS One. 2013; 8(2): e5), with the minimum colony radius set to 3, the maximum colony radius set to 50, and the regular threshold set to 4.

The same assay as above was also used to assess the mutation rate of the ugi rApol, ugi MutaT7, and ugi drApol-T7 strains (TABLE 8), except that instead of arabinose either 0 mM or 1 mM isopropyl b-D-l-thiogalactopyranoside (IPTG) was added to the liquid overnight cultures as a control or to induce mutagenesis, respectively.

TABLE 8. Strain table. The genotypes of strains used in this work are shown.

The“xoy” notation indicates a replacement of“x” with“y” through lambda red recombineering.

Chemical Mutagenesis with ethyl methane sulfonate (EMS): Mutagenesis with EMS was performed as previously described (Cupples and Miller, Proc. Natl. Acad. Sci. U.S.A. 1989 Jul; 86(14): 5345-49). An overnight culture of each sample was subcultured and grown until it reached a density of 2-3 x 10 ⁸ cells per mL (log phase). 5 mL aliquots of cells were chilled on ice, washed twice with sodium phosphate buffer (pH = 7), and resuspended in 1 mL of lx PBS in a 1.5 mL Eppendorf tube. EMS was added while cold by pipetting 14 pL of EMS into 1 ml of resuspended cells. Eppendorfs were sealed and mixed at 1000 r.p.m. for 60 min at 37 °C. The cells were then washed twice with LB and resuspended in 1 mL of LB. Immediately after washing, a viability measurement was performed by plating 50 pL of a 10, 000-fold dilution of each culture on LB agar with 100 pg/mL streptomycin, 100 pg/mL ampicillin, and 50 pg/mL tetrazolium chloride. After 48 h of incubation, plates were imaged on a document scanner as described above. The number of live ampicillin resistant colonies were counted after EMS treatment in CFU/mL to measure the viability after mutagen treatment (FIG. 13D). For mutation rate assessment, 500 m L of the post-EMS-treated resuspension was inoculated into 5 ml of FB with 100 pg/mF streptomycin and 100 pg/mF ampicillin. The cultures were grown at 37 °C for 20 h, then 50 pF of each culture was plated on FB agar with 50 pg/mF tetrazolium chloride and 100 pg/mF rifampicin. 50 pF of a 100, 000-fold dilution of each culture was also plated on FB agar with 100 pg/mF

streptomycin, 100 pg/mF ampicillin, and 50 pg/mF tetrazolium chloride. After 48 h of incubation, plates were imaged on a document scanner as described above. The number of rifampicin resistant mutants in CFU/mF was divided by the number of live ampicillin resistant cells in CFU/mF for each sample to obtain the rifampicin resistant mutation frequency (FIG. 13D).

Continuous Culturing and Sequencing of the Dual T7 Promoter Reporter Plasmid : The dual T7 promoter reporter plasmid was continuously cultured in the MutaT7-csg ⁺ mot ⁺ strain (TABFE 8) in a 70 mL culture in a round-bottomed flask that was slowly stirred in a 37 °C mineral oil bath. The culture was aerated through a needle that was connected to a standard aquarium pump and FB with 100 pg/mF streptomycin, 100 pg/mF ampicillin, and 0.5% isopropanol (as an antifoaming agent) was fed into the culture via a needle connected to a peristaltic pump at a rate of -0.5 volumes/h. Fractions were collected every 3 d for 12 d. Each fraction was plated for single colonies on FB agar with 100 pg/mF ampicillin and 10 clones from each fraction were Sanger-sequenced by colony PCR with the primers 1493 and 1494 (TABFE 10).

Continuous Culturing and Sequencing of the T7 Promoter + Filler DNA and T7 Promoter + Terminators Reporter Plasmids Reporter Plasmids. The T7 promoter + filler DNA and T7 promoter + terminators reporter plasmids were continuously cultured in the Aung (negative control), MutaT7, and MP6 strains (TABFE 8) in 20 mL cultures using a previously described multiplex bioreactor setup (Miller et al.., J. Vis. Exp. 2013 Feb 23; (72): e50262). The reactor was stored in a 37 °C warm room and was aerated and stirred with aquarium pumps. FB with 100 pg/mF streptomycin, 100 pg/mF ampicillin, 100 pg/mF cycloheximide, 0.01% (v/v) antifoam-204, and 150 pg/mF arabinose (+10 pg/mF

chloramphenicol in the case of the MP6 strain (TABFE 8)) was pumped into each reaction vessel at a rate of 0.87 volumes/h. Fractions were collected every 3 d. Each fraction was plated on LB agar with 100 pg/mL streptomycin and 100 pg/mL ampicillin and 12 single colonies from each plate were grown in 5 mL LB with 100 pg/mL ampicillin. DNA was isolated from each overnight culture using the Qiaprep 96 Turbo Miniprep Kit and quantified using the PicoGreen assay.

Library Construction and Next Generation Sequencing : Libraries were prepared using a miniaturized version of Nextera XT. Briefly, 0.5 ng of input DNA was subjected to a 1/12 scale reaction of Illumina Nextera XT performed on a TTP Labtech Mosquito HV using combinatorial dual indexing (Vfmai = 4 pl). Completed libraries were size selected using SPRI beads at 0.7x volume and pooled before sequencing on an Illumina MiSeq using 150 nt paired end reads (v2 chemistry). Sequencing reads were aligned against respective plasmid sequences using bwa mem (v. 0.7.l2-rl039) (Li, arXiv preprint arXiv. 16 Mar

20l3;l303.3997), with flag -t 16, and sorted and indexed bam files were generated using samtools (v 1.3) (Li et al., Bioinformatics. 2009 Aug 15; 25(16): 2078-79). These bam files were processed using samtools mpileup with flags -excl-flags 2052, -d 10000000 and the same plasmid reference sequences used for mapping (Li et al.., Bioinformatics. 2011 Nov 1; 27(21): 2987-93). Read coverages and alleles counts and frequencies were tabulated at each position of the reference sequence in each sample for down-stream analysis. Only positions with greater than lO-fold coverage in all replicates of each sample were included in the analysis. Fixed variant alleles (present at greater than 85% frequency) for each sample are reported. Sanger sequencing was also performed on a PCR amplicon from 96 clones of Aung (negative control) and MutaT7 strains (TABLE 8) after 15 d of continuous culture carrying the T7 promoter + terminators reporter plasmid. The primers 2165 and 1197 (TABLE 10) were used to amplify and Sanger sequence the Kan ^R gene.

Lambda Red Recombineering : The E. coli genome was edited using seamless lambda red recombineering with ccdB counterselection, as previously described (Wang et al., Nucleic Acids Res. 2014 Mar; 42(5): e37). Cells were transformed with the temperature-sensitive psclOl-gbaA recombineering plasmid, plated on LB agar with 10 pg/mL tetracycline, and incubated for 24 h at 30 °C. Colonies were selected and grown in LB containing 10 pg/mL tetracycline overnight at 30 °C (18-21 h). Overnight cultures were diluted 25-fold in LB with 10 pg/mL tetracycline and grown at 30 °C for ~2 h until attaining an ODeoo of 0.3-0.4. The ccdA antitoxin and recombineering machinery were then induced by adding arabinose and rhamnose to a final concentration of 2 mg/mL each and then growing the cultures at 37 °C for 40 min to an ODeoo of -0.6. The cultures were then placed on ice, washed twice with ice-cold sterile ddH20, resuspended in -25 pL of ice-cold sterile ddH ₂ 0, and electroporated with -200 ng of the appropriate kan-ccdB targeting cassette (1.8 kV, 5.8 ms, 0.1 cm cuvette, BioRad Micropulser). The cells were then recovered in super optimal broth with catabolite repression (SOC) with 2 mg/mL arabinose at 30 °C for 2 h, then plated on LB agar plates with 50 pg/mL kanamycin and 2 mg/mL arabinose and incubated for 24 h at 30 °C. Colonies that grew under these conditions had incorporated the kan-ccdB targeting cassette and were picked and grown in LB with 50 pg/mL kanamycin and 2 mg/mL arabinose at 30 °C for 18- 21 h. The cultures were then diluted 25-fold in LB with 50 pg/mL kanamycin and 2 mg/mL arabinose and grown at 30 °C for -2 h until they reached an ODeoo of 0.3-0.4. The recombineering machinery was then induced by adding rhamnose to a final concentration of 2 mg/mL and then growing the cultures at 37 °C for 40 min to an ODeoo of -0.6. The cultures were then placed on ice, washed twice with ice-cold sterile ddH20, resuspended in -25 pL of ice-cold sterile ddH ₂ 0, and electroporated with -200 ng of the final targeting cassette intended to replace the kan-ccdB cassette currently integrated in the genome (1.8 kV, 5.8 ms, 0.1 cm cuvette, Bio-Rad Micropulser). The cells were then recovered in SOC with 2 mg/mL arabinose at 30C for 2 h, and then were washed once with LB to remove the arabinose and prevent continued production of the ccdA antitoxin. The cultures were then plated on LB agar plates at various dilutions with 100 pg/mL streptomycin and incubated for 24 h at 37 °C. Without the ccdA antitoxin, the ccdB toxin will kill cells that have not replaced the integrated kan-ccdB cassette with the final targeting cassette. The colonies that grow should have the final targeting cassette integrated, but were screened by PCR or sequencing to confirm cassette integration as some colonies may simply inactive the ccdB toxin. Once a clone with the desired change was found, the temperature- sensitive psclOl-gbaA recombineering plasmid was cured by plating on LB agar with 100 pg/mL streptomycin, incubating at 42 °C for 18-21 h, streaking a colony from the plate on LB agar with 100 pg/mL streptomycin, and incubating at 42 °C for another 18-21 h. The colonies from the second plate were grown in LB with 100 pg/mL streptomycin at 37 °C to generate glycerol stocks. The colonies were also incubated in LB with 10 pg/mL tetracycline at 30 °C to ensure tetracycline sensitivity and confirm that the recombineering plasmid was successfully cured. The various strains used in this work (TABLE 8) were generated using the primers in TABLE 10.

TABFE 9: Fist of strain modifications.

Deleting the motAB and csgABCDEFG operons through DIRex lambda red recombineering to decrease biofilm formation in bioreactor experiments. Deletions of the motAB operon (Pratt and Kolter, Mol. Microbiol. 1998 Oct; 30(2): 285-93) and the csgABCDEFG (Prigent-Combaret et al., Environ. Microbiol. 2000 Aug; 2(4): 450-64) have been shown to produce strains of E. coli that are deficient in biofilm formation. To minimize inlet line contamination and clogs in bioreactor experiments owing to biofilms, the motAB and csgABCDEFG operons were deleted using one-step DIRex lambda red recombineering (Nasvall, PLoS One. 2017 Aug 30; 12(8): e0l84l26). The motAB targeting half-cassettes were amplified from R6K-AmilCP-kan-ccdB using the primers delmotDF and AmilCP-KanR and from R6K-kan-ccdB-AmilCP using the primers del-motDR and KanF-AmilCP (TABFE 10). The motAB half cassettes were co-electroporated to replace motAB with a kan-ccdB cassette flanked by large AmilCP inverted repeats nested between short 30 bp direct repeats. The repeat architecture leads to a high rate of spontaneous excision that was selected for using ccdB counterselection to obtain a markerless deletion of motAB. This procedure was then repeated to delete the csgABCDEFG operon. The csgABCDEFG targeting half-cassettes were amplified from R6K-AmilCP-kan-ccdB using the primers delcsgDF and AmilCP-KanR and from R6K-kan-ccdB -AmilCP using the primers delcsgDR and KanF-AmilCP (TABFE

10).

TABLE 10. Primer and oligo table. Primers used for lambda red

recombineering, restriction cloning of the terminator arrays, colony PCR, and Sanger sequencing.

Separation of rApol-T7 fusion (rApol + T7) through DIRex lambda red

recombineering : In order to generate a non-fusion control strain in which rApol (or drApol) and T7 are expressed separately from the same operon under the PAli _ac o- _Te n _th promoter, one- step DIRex lambda red recombineering was used to insert a stop codon at the end of the rApol gene. The rApolStop targeting half-cassettes were amplified from R6K-AmilCP-kan- ccdB using the primers rApolStopDF and AmilCP-KanR and from R6K-kan-ccdB-AmilCP using the primers rApolStopDR and KanF-AmilCP (TABLE 10). The rApolStop half cassettes were co-electroporated to insert a stop codon after rApol followed by a kan-ccdB cassette flanked by large AmilCP inverted repeats nested between short 30 bp direct repeats. Excision of the AmilCP-kan-ccdB -AmilCP cassette was selected for using ccdB

counterselection to obtain a markerless insertion of a stop codon after rApol.

Mutation Assay and Sequencing with the T7 Promoter + rpsL Reporter Plasmid : To assess the locations and types of mutations observed, the drApol-T7 negative control strain and MutaT7 and MP6 mutagenic strains (TABLE 8) (Strep ^R ) carrying the T7 promoter -1-rpsL reporter plasmid (Amp ^R ) were streaked on LB agar with 100 pg/mL ampicillin and grown at 37 °C for 24 h in order to obtain clones. Single colonies were picked in triplicate for each sample and used to inoculate 5 mL LB with 100 pg/mL ampicillin and 25 mM arabinose (with 10 pg/mL chloramphenicol for the MP6 strain, TABLE 8), then shaken at 250 r.p.m. and 37 °C for 24 h to accumulate mutations during growth. 1 mL aliquots of each culture were pelleted at 6000 x g for 3 min and resuspended in 1 mL LB to remove arabinose. 50 pL of a lOO-fold dilution of each resuspension was plated on LB Lennox agar plates (pH 8.0) with 500 pg/mL streptomycin, 100 pg/mL ampicillin, and 50 pg/mL tetrazolium chloride. 48 colonies from each plate were picked for colony PCR using the primers 2062 and 1197 (TABLE 10). The amplicons were Sanger-sequenced using the primer 1197 (TABLE 10).

LacZa Activity Assay for Quantifying T7 and MutaT7 Processivity: In order to determine if the fusion of rApol to the N-terminus of T7 RNA polymerase affected the processivity and/or activity of the T7 RNA polymerase, the expression of the lacZa fragment from T7 promoters of varying upstream distances was measured via the cleavage of o- Nitrophenyl-P-galactoside (oNPG) using an assay adapted from a previous publication (Schaefer et ah, Anal. Biochem. 2016 Mar 29; 503: 56-57). LacZa reporter plasmids C1A through C1F (ChlorR) were transformed into the ung ⁺ , drApol-T7 ung ⁺ and drApol+T7 ung ⁺ strains (TABLE 8) and plated on LB agar with 25 pg/mL chloramphenicol and grown at 37 °C for 24 h in order to obtain clones. Colonies of each reporter/strain combination were picked in triplicate and grown in 200 pL LB with 25 pg/mL chloramphenicol and 1 mM IPTG in a parafilm-wrapped 96-well plate that was shaken at 220 r.p.m. at 30 °C for 22 h. IPTG was added to induce the expression of the lacZa fragment from the genome that complements the lacZa fragment, and to increase the expression of drApol-T7 and T7 from the P _Aiiac o-Tenth promoter. 80 pL of each overnight culture was mixed with 120 pL Bgal mix (60 mM sodium dibasic, 40 mM sodium phosphate monobasic, 10 mM potassium chloride, 1 mM magnesium sulfate, 26 mM 2-mercaptoethanol, 166 pg/mL egg-white lysozyme, 1.0 mg/mL oNPG, and 6.7% PopCulture lysis reagent) in a black, clear-bottomed 96-well plate. The ODeoo and OD ₄₂ o of each well was measured every 2 min over the course of 1 h in a Biotek Synergy Hl hybrid plate reader followed by double orbital shaking at 559 r.p.m. at 30 °C. The oNPG cleavage activity of each well was calculated by measuring the slope of the linear region of each OD ₄₂ o trace, dividing by the initial ODeoo reading, and multiplying by 1000. The mean and standard deviation of each set of triplicates were calculated.

Episomal folA Directed Evolution Assay to Assess False Positive Frequency : To assess the effect that targeted versus global mutagenesis has on the false positive frequency of a directed evolution experiment, a model drug resistance evolution experiment was designed where the rate of true positive evolution corresponds to the frequency that drug resistance- conferring mutations appear in an episomal copy of a drug-sensitive gene. To create this system, thc /oM+T7 promoter plasmid (Amp ^R )— which contains the complete, endogenous folA promoter and coding sequence for dihydrofolate reductase followed by a T7 promoter pointing in the reverse direction— was transformed into MutaT7 and MP6 mutagenic strains (TABLE 8) (Strep ^R ). These strains were streaked on LB agar with 100 pg/mL ampicillin and grown at 37 °C for 24 h in order to obtain clones. Single colonies were picked in triplicate for each sample and used to inoculate 5 mL LB with 100 pg/mL ampicillin and 25 mM arabinose (with 10 pg/mL chloramphenicol for the MP6 strain (TABLE 8)), then shaken at 250 r.p.m. and 37 °C for 24 h to accumulate mutations during growth. 1 mL aliquots of each culture were pelleted at 6000 x g for 3 min and resuspended in 1 mL LB to remove arabinose. 50 pL of a lOO-fold dilution of each resuspension was plated on LB agar plates with 5 pg/mL trimethoprim (TMP) and 50 pg/mL tetrazolium chloride. 13-15 colo-nies from each plate were picked for colony PCR. Episomal folA was amplified and Sanger sequenced using the primers Alof-T7 S and 1197 (TABLE 10).

TABLE 11. Sanger sequencing data for FIGs. 21A-21B.

Bacterial growth assay measuring trimethoprim drug resistance : Isolates were grown to stationary phase following overnight incubation at 37 °C in LB with 100 pg/mL ampicillin. Cultures were diluted 1:100 into a plate containing LB broth with increasing concentrations of TMP ranging from 1 mM to 1 mM. Growth of diluted samples was determined by measuring ODeoo every 5 min in a Biotek Synergy Hl hybrid plate reader followed by orbital shaking at 282 r.p.m. and incubation at 37 °C. Maximal growth rate was determined by performing“Max V” calculation in Gen5 software, using a 5-point segment of each growth curve corresponding to the highest linear slope. Upon determining maximum growth rate within each sample, growth rates were normalized to the highest growth rate within each sample series yielding the relative growth rate at each TMP concentration (FIGs. 21A-21B).

Example 9: Design of Chimeric MutaT7 Protein.

Traditional in vivo mutagenesis strategies rely on exogenous mutagens (e.g., high energy light or chemicals) (Cupples et ah, Proc. Natl. Acad. Sci. U.S.A. 1989 Jul; 86(14): 5345-49; Tessman et ah, 1965 Apr 23; 148(3669): 507-8) or expressing mutagenic enzymes (e.g., XLl-Red (Greener et ah, Mol. Biotechnol. 1997 Apr; 7(2): 189-95) or the MP6 plasmid (Badran A.H. and Liu D.R., Nat. Commun. 2015 Oct 7; 6: 8425)). These global mutagenesis strategies can yield high mutation rates and diverse genetic landscapes. However, extensive mutations throughout the genome are problematic in many contexts, especially in directed evolution experiments (FIG. 12A). Off-target mutations outside the intended DNA region are often toxic when they occur in essential portions of the genome (Gerdes et ah, J. Bacteriol. 2003 Oct; 185(19): 5673-84; Wang et ah, Science. 2015 Nov 27; 350(6264): 1096-101), a problem that limits library size and engenders rapid silencing of mutagenic plasmids. Global mutagens also introduce“parasite” variants into DNA libraries, originating from mutations outside the gene of interest that allow an organism to circumvent selection schemes (Tizei et ah, Biochem. Soc. Trans. 2016 Aug 15; 44(4): 1165-1175).

Targeted in vivo mutagenesis strategies have the potential to overcome these deficiencies. DNA-damaging enzymes fused to deactivated Cas9 nucleases can edit bases at specific genetic loci (Komor et al., Nature. 2016 May 19; 533(7603): 420-24; Nishida et al., Science. 2016 Sep 16; 353(6305): pii: aaf8729; Komor et al., Sci. Adv. 2017 Aug 30; 3(8): eaao4774; Gaudelli et al., Nature. 2017 Nov 23; 551(7681): 464-71; Kim et al., Nat.

Biotechnol. 2017 Apr 10; 35(5): 475-480), but require many gRNAs to tile mutagenic enzymes throughout a target DNA that may be multi-kb in length (Hess et al., Nat. Methods. 2016 Dec; 13(12): 1036-42; Ma et al.., Nat. Methods. 2016 Dec; 13(12): 1029-35). Moreover, the guide RNAs must be redesigned after each evolution round introduces new mutations in the target DNA. Another example is the use of an error-prone poll variant to selectively mutagenize genes on ColEl plasmids, although this method is limited to Escherichia coli and can target mutations within only a few kb of the ColEl origin (Camps et al., Proc. Natl. Acad. Sci. U.S.A. 2003 Aug 8; 100(17): 9727-9732; Allen et al., Nucleic Acids Res. 2011 May 26; 39(16): 7020-7033). Error-prone replication mediated by the Tyl retrotransposon specifically in yeast can also selectively mutate <5 kb genetic cargoes inserted into the retrotransposon (Crook et al., Nat. Commun. 2016 Oct 17; 7: 13051). Other targeted mutation methods in yeast include oligo-mediated genome engineering (DiCarlo et al., ACS Synth. Biol. 2013 Dec 20; 2(12): 741-749), which can be labor-intensive, and an orthogonal replication system (Ravikumar et al., Nat. Chem. Biol. 2014 Feb 2; 10(3): 175-177), which was developed specifically in yeast.

It was hypothesized herein that a processive, DNA-traversing biomolecule tethered to a DNA-damaging enzyme could provide a generalizable solution to the problem of targeting mutations across large, yet still well-defined, DNA regions. Monomeric RNA polymerases possess inherently high promoter specificity (Rong et al., J. Biol. Chem. 1998 Apr 24;

273(17): 10253-60) and processivity (Thiel et al., J. Gen. Virol. 2001 Jun; 82(6): 1273-81). Cytidine deaminases are potent DNA-damaging enzymes that can act on single-stranded DNA substrates during transcription (Ramiro et al., Nat. Immunol. 2003 May; 4(5): 452-56). We envisioned that a chimeric“MutaT7” protein consisting of a cytidine deaminase (rApol) fused to T7 RNA polymerase (T7-pol) would, therefore, allow us to target mutations specifically to any DNA region lying downstream of a T7 promoter (FIG. 12B), provided the T7 promoter is not present elsewhere in the genome.

To begin, a lacZ expression assay (Schaefer et al., Anal. Biochem. 2016 Mar 29; 503: 56-57) was used to show that T7-Pol tolerated an rApol N-terminal fusion and still efficiently transcribed tens of kilobases (FIGs. 15A-15B). Next, the MutaT7 gene was integrated under control of a weak promoter into the genome of E. coli lacking uracil N- glycosylase (Aung) (FIGs. 16A-16B and TABLE 8). Deleting ung inhibits repair of deoxyuridine to deoxycytidine and increases mutagenesis rates (Nilsen et al., Mol. Cell. 2000 Jun; 5(6): 1059-1065; Alspe et al., Sci. Rep. 2017 Aug 3; 7(1): 719), especially in the context of cytidine deaminases (Petersen-Mahrt et al., Nature. 2002 Jul 4; 418(6893): 99-103).

Example 10: Characterization of Targeted Mutagenesis of MutaT7.

Targeted mutagenesis was assayed using a codon reversion assay based on reporter plasmids either having or lacking a T7 promoter sequence upstream of silent drug resistance genes with ACG triplets in place of ATG start codons (FIG. 13A, FIG. 17, FIG. 18, FIG. 19A). The kanamycin resistance gene (Kan ^R ) was placed immediately downstream of the T7 promoter. In this assay, successful C to T mutagenesis at the Kan ^R start codon yields kanamycin-resistant colonies. Global mutagens such as the MP6 plasmid yielded high levels of kanamycin-resistant colonies regardless of the T7 promoter, consistent with a lack of promoter-based targeting (FIG. 13B). In contrast, MutaT7 strains attained significant kanamycin resistance only when reporter plasmids possessed a T7 promoter upstream of the Kan ^R gene (FIG. 13B). Expression of a catalytically dead version of MutaT7 (drApol-T7) (Navaratnam et al., Cell. 1995 Apr 21; 81(2): 187-95) yielded kanamycin resistance frequencies similar to background levels, indicating that T7 activity alone was not responsible for the observed increase in kanamycin resistance (FIG. 13B).

T7 promoter-dependent Kan ^R mutagenesis by MutaT7 shows that mutagenesis can be targeted to a desired DNA region near a T7 promoter. Because T7-pol is highly processive, it was anticipated that mutations would also be introduced further downstream of the T7 promoter. MutaT7 processivity was assayed by inserting a tetracycline-resistance (Tel ^R ) gene with an inactive, ACG start codon -1.6 kb downstream of the Kan ^R gene (FIG. 13A). High levels of MutaT7-dependent tetracycline resistance were observed only in reporter strains having the T7 promoter, consistent with targeted and processive introduction of mutations across a lengthy, multi-kb DNA region (FIG. 13B). Global mutagens again generated tetracycline -resistant colonies at high frequency in all cases, irrespective of the T7 promoter (FIG. 13B).

Targeted mutagenesis using the processive MutaT7 chimera requires not just recruitment to a DNA locus, but also termination at the end of targeted DNA. To address termination, KarPlTeP reporter plasmids were used in which the silent, start codon-defective resistance genes were separated by one or more T7 terminators (FIG. 13A). Upon assaying for drug resistance, it was found that four copies of the T7 terminator fully constrained mutagenesis to the intended upstream Kan ^R gene (FIG. 20). Using this terminator array, tetracycline resistance was observed for MutaT7 strains similar to background levels, whereas kanamycin resistance remained high (FIG. 13B). Global mutagens again induced high levels of kanamycin- and tetracycline-resistance, irrespective of the terminator array (FIG. 13B).

To further assess whether MutaT7 induces mutagenesis specifically on the target DNA, the evolution of resistance to rifampicin (Garibyan et ah, DNA Repair. 2003 May;

2(5): 593-8) and fosfomycin (Nilsson et ah, Antimicrob. Agents Chemother. 2003 Sep; 47(9): 2850-58) was evaluated. Resistance can derive from diverse genomic mutations such that the appearance of resistant colonies correlates with off-target mutation rates in the genome (Badran and Liu, Nat. Commun. 2015 Oct 7; 6: 8425; Garibyan et ah, DNA Repair. 2003 May; 2(5): 593-8), analogous to cheating parasites in directed evolution schemes. Selection on either rifampicin- or fosfomycin-treated plates revealed that MutaT7-expressing samples displayed drug resistance frequencies comparable to background. In contrast, high

frequencies of antibiotic resistance were observed in all global mutagenesis samples (FIG. 13C and FIGs. 19B-19C).

Additional experiments were directed at using MutaT7 to evolve ectopic ally expressed folA gene variants that confer trimethoprim resistance. Th efolA gene encodes dihydrofolate reductase, and folA mutations are just one of many potential routes to trimethoprim resistance (Acar and Goldstein, Rev. Infect. Dis. 1982 Mar- Apr 4; 4(2): 270- 275). Either global mutagenesis or MutaT7 was used to mutagenize E. coll carrying a T7- targeted episomal copy of folA. Sanger- sequencing was then performed on colonies that grew on trimethoprim plates. 29 of 44 trimethoprim-resistant colonies mutagenized using MutaT7 had a mutation known to confer resistance (Herrington et ah, J. Basic Microbiol. 2002; 42(3): 172) in the episomal folA promoter (TABLE 9, FIGs. 21A-21B). In contrast, none of the 43 trimethoprim-resistant colonies obtained using the global mutagen contained mutations in the episomal /oM gene. Instead, they presumably gained trimethoprim resistance via undesired mutations in the E. coli genome. The ability of MutaT7 to generate a high rate of true positives in the desired episomal gene target, whereas global mutagenesis exclusively generated cheaters (false positives), highlights a key advantage of MutaT7.

DNA sequencing was then used to better understand the processivity and targeting of MutaT7 mutagenesis. An E. coli population expressing MutaT7 and the episomal Kan ^K /Tel ^K reporter plasmid was allowed to drift in the absence of selection pressure for 15 days prior to isolation of episomal DNA from clones (FIG. 14A). Sanger sequencing of the target episomal region revealed mutations at multiple loci throughout the Kan ^R target gene, independent of selection pressure (FIG. 22). In a separate experiment where the target DNA consisted of an episomal rpsL allele (initially sensitive to streptomycin) downstream of a T7 promoter (FIG. 23A), the processivity of MutaT7 was further evaluated. Sanger sequencing of streptomycin- resistant DNA isolated from a MutaT7-expressing strain of E. coli again revealed that multiple mutations appeared throughout the targeted rpsL gene, with -90% C to T mutations and -10% G to A mutations (FIG. 23B).

Example 11: Characterization of MutaT7 Toxicity.

Another benefit of targeted mutagenesis is the capacity to attain much larger library sizes by avoiding toxic mutations in essential, off-target genes. On the basis of the apparently low off-target mutagenesis rate of MutaT7, it was hypothesized that E. coli carrying MutaT7 would have significantly higher viability than bacteria treated with global mutagens. Indeed, consistent with prior work (Badran and Liu, Nat. Commun. 2015 Oct 7; 6: 8425), a very low viability was observed in all populations treated with global mutagens. In contrast, populations expressing MutaT7 possessed viability similar to untreated cells (FIG. 13D and FIG. 19D). The total number of kanamycin-resistant colonies was similar between MutaT7 and globally mutagenized samples (FIG. 13E) despite the somewhat lower mutagenesis rate of the MutaT7 construct relative to MP6 (FIG. 13B; the average kanamycin resistance frequency for MutaT7 was 6.7 x 10 ⁶ versus 5.7 x 10 ⁵ for MP6). This observation highlights that the use of MutaT7 to maximize on-target mutations while simultaneously minimizing off-target mutations results in larger productive library sizes. Example 12: Characterization of MutaT7 On- and Off- Mutation Rates.

Next, Illumina sequencing was used to identify mutations anywhere in the episomal reporter DNA sequence obtained from clones of the E. coli populations in FIG. 14A. This experiment assesses on- versus off-target mutagenesis across a -10 kb stretch of DNA containing only ~l kb of intended target DNA. MutaT7 samples displayed many mutations throughout the episome when the terminator array was removed but the T7 promoter was maintained (FIG. 14B). Treatment with the MP6 global mutagen also led to mutations throughout the entire episomal DNA. In contrast, mutations in MutaT7 strains appeared almost exclusively within the Kan ^R target gene when both a promoter and terminator array were present, even after 15 days of continuous culturing (FIG. 14B). Upon normalizing on- and off-target mutation rates, it was observed that the few off-target mutations found on plasmids with a terminator from MutaT7 strains were present only to the same extent as in the control sample not treated with any mutagen (FIG. 14C).

A disadvantage of MutaT7 is its limited mutational spectrum and an apparent strand bias observed in the sequencing results showing that C to T transitions were predominantly obtained in the sense strand using a single T7 promoter (FIG. 14C). It was hypothesized that the mutational spectrum could be doubled by introducing a second T7 promoter that would recruit MutaT7 to the 3 '-end of the target DNA and enable processive activity in the opposing direction. Indeed, installing an additional antisense T7 promoter led to the accumulation of both G to A and C to T mutations throughout the target gene during continuous culturing (FIGs. 24A-24B). Furthermore, the average number and range of mutations per clone increased over time (FIG. 24C). The latter observation indicates that, in contrast to global mutagenesis methods where the organism often rapidly silences mutagen expression, the high on-target to off-target mutation ratio of MutaT7 enabled long-term maintenance of mutagen expression in cells.

It was also observed that repair of deoxyuridine must be prevented to observe significant mutagenesis with MutaT7 (also observed with other cytidine deaminase-based systems (Badran and Fiu, Nat. Commun. 2015 Oct 7; 6: 8425; Komor et al., Nature. 2016 May 19; 533(7603): 420-24)). Although Aung cells were used to address this issue in the aforementioned experiments, a more flexible alternative is to co-express MutaT7 with the uracil glycosylase inhibitor (UGI; a protein that can inhibit UNG activity in many prokaryotes and eukaryotes (Badran and Fiu, Nat. Commun. 2015 Oct 7; 6: 8425; Komor et ah, Nature. 2016 May 19; 533(7603): 420-24; Serrano-Heras et ah, Nucleic Acids Res. 2007 Aug 13; 35(16): 5393-5401)). Such co-expression resulted in a high rate of mutagenesis similar to that achieved using Aung cells (FIGs. 25A-25C). UGI thus eliminates the need to delete ung to achieve efficient mutagenesis with MutaT7, significantly increasing the flexibility of the system.

In summary, the processively-acting MutaT7 chimera can selectively direct mutations to large, yet well-defined, regions of DNA in vivo. Utilizing other base editing enzymes (Gaudelli et al., Nature. 2017 Nov 23; 551(7681): 464-71) in concert with cytidine deaminase will significantly widen the mutational spectrum of MutaT7 and further enable the creation of rich and diverse DNA libraries in vivo. Moreover, DNA-modifiers fused to T7 could facilitate targeted epigenetic studies (DeNizio et al., Curr. Opin. Chem. Biol. 2018 Feb 13; 45: 10-17). The ubiquitous applicability of T7-pol in diverse organisms (McBride et al., Proc. Natl. Acad. Sci. U.S.A. 1994 Jul 19; 91(15): 7301-7305; Lieber et al., Eur. J. Biochem., 1998 Oct 1; 217(1): 387-94; Weinstock et al., Nat. Methods. 2016 Aug 29; 13(10): 849-851; Dower and Rosbash, RNA. 2002 May; 8(5): 686-697) suggests that MutaT7 will prove useful in a broad range of evolutionary and synthetic biology settings.

Example 13: Materials and Methods for Example 14.

The following strains were constructed using lambda red recombineering as described in Example 8.

TABLE 12. Strain table. The genotypes of strains used in this work are

shown. The“xoy” notation indicates a replacement of“x” with“y”

through lambda red recombineering. To assess mutagenesis rates, the control (tadA-Only) and mutagenic strains (tadA- XTEN-T7 and tadA-GGS-T7) (Strep ^R ) carrying reporter plasmids (BAC-KanStop-TetStop or BAC-T7-KanStop-TetStop, FIG. 26A) (Amp ^R ) were streaked on LB agar with 100 pg/mL streptomycin and 100 pg/mL ampicillin and grown at 37 °C for 24 h in order to obtain clones. Single colonies were picked for each sample and used to inoculate 5 mL LB with 100 pg/mL streptomycin, 100 pg/mL ampicillin with or without lmM IPTG, then shaken at 250 r.p.m. and 37 °C for 24 h to accumulate mutations during growth. 1 mL aliquots of each culture were pelleted at 10000 x g for 3 min and resuspended in 1 mL LB to remove IPTG. Each resuspension was plated on LB agar plates with 50 pg/mL tetrazolium chloride (a metabolic contrast dye for visualizing colonies) and the antibiotics indicated below to analyze mutations rates and viability:

• 50 pL of a 100, 000-fold dilution of each resuspension was plated on LB agar with 100 pg/mL streptomycin, 100 pg/mL ampicillin, and 50 pg/mL tetrazolium chloride. The colony counts from these plates were used to calculate the cell viability (i.e., the number of live, ampicillin resistant cells) in CFU/mL for each sample (FIG. 26D).

• 50 pL of each resuspension was plated on LB agar plates with 200 pg/mL kanamycin and 50 pg/mL tetrazolium chloride. The colony counts from these plates were used to calculate the number of kanamycin resistant mutants in CFU/mL for each sample. The number of kanamycin resistant mutants in CFU/mL was divided by the number of live ampicillin resistant cells in CFU/mL for each sample to obtain the kanamycin resistant mutation frequency (FIG. 26B).

• 50 pL of each resuspension was plated on LB agar plates with 20 pg/mL tetracycline and 50 pg/mL tetrazolium chloride. The colony counts from these plates were used to calculate the number of tetracycline resistant mutants in CFU/mL for each sample.

The number of tetracycline resistant mutants in CFU/mL was divided by the number of live ampicillin resistant cells in CFU/mL for each sample to obtain the tetracycline resistant mutation frequency (FIG. 26B).

• 50 pL of each resuspension was plated on LB agar plates with 100 pg/mL rifampicin and 50 pg/mL tetrazolium chloride. The colony counts from these plates were used to calculate the number of rifampicin resistant mutants in CFU/mL for each sample. The number of rifampicin resistant mutants in CFU/mL was divided by the number of live ampicillin resistant cells in CFU/mL for each sample to obtain the rifampicin resistant mutation frequency (FIG. 26C). Plates were incubated at 37 °C for 48 h, then imaged by inverting the plates onto transparencies and scanning on a document scanner at a resolution of 400 dots per inch. The colonies were then counted using the software OpenCFU (3.9.0) (Geissmann, PLoS One. 2013; 8(2): e54072), with the minimum colony radius set to 3, the maximum colony radius set to 50, and the regular threshold set to 4.

Example 14: Characterization of TadA Fusion Proteins.

To show that other types of mutations can be introduced using other DNA damaging agents fused to T7, a previously reported variant of tadA (Gaudelli et al., Nature. 2017 Nov 23; 551(7681): 464-71, the entirety of which is incorporated herein by reference) was fused to T7 using two different linker sequences (GGS and XTEN) and placed under the control of an IPTG-inducible promoter (PAllacO-Tenth). This variant of tadA is able to make A to G mutations in DNA.

Mutagenesis assays were then carried out using these tadA-T7 E. coli strains and reporter plasmids that have defective resistance genes. For these assays, reporter plasmids were used that have defective kanamycin (Kan ^R ) and tetracycline (Tet ^R ) resistance genes (each having premature TAG stop codons). The BAC-KanStop-TetStop reporter plasmid lacks a T7 promoter, and should thus not be targeted by the tadA-XTEN-T7 or tadA-GGS-T7 fusion enzymes. The BAC-T7-KanStop-TetStop reporter plasmid has a T7 promoter preceding the defective KanR and TetR genes, which should allow tadA-XTEN-T7 or tadA- GGS-T7 fusion enzymes to mutate these genes, occasionally mutating the TAG stop codon to TGG and thus conferring antibiotic resistance (FIG. 26 A).

Without the T7 promoter on the reporter plasmid, only a low level of resistance- conferring mutations were observed across all conditions, including with the tadA-Only control strain, which only expresses the tadA enzyme alone (FIG. 26B). A high level of mutagenesis was observed when the tadA-XTEN-T7 or tadA-GGS-T7 fusion enzymes were induced with 1 mM IPTG and when the reporter plasmid contained a T7 promoter, suggesting that the tadA-XTEN-T7 or tadA-GGS-T7 fusion enzymes specifically introduce A to G mutations downstream from a T7 promoter.

Furthermore, low levels of rifampicin resistance were observed across all conditions (FIG. 26C). The fact that very few rifampicin resistance-conferring mutations are occurring in the E. coli genome across all conditions suggests that the tadA-XTEN-T7 or tadA-GGS-T7 fusion enzymes have minimal off-target activity relative to the tadA-Only control. Finally, under most conditions, the expression of tadA-XTEN-T7 or tadA-GGS-T7 fusion enzymes did not negatively impact cell viability (FIG. 26D).

Example 15: Applications of Dynamic Targeted Hypermutation.

DNA mutagenesis is an important and necessary step in all directed evolution methodologies, which are heavily utilized by academic and industrial labs around the world. Mutagenic technologies are particularly vital for research labs developing biomolecular drugs with novel actions or improved potency, as the identification of biomolecules with improved therapeutic properties inherently relies on some form of directed evolution. The recent implementation of biologies has further increased the demand for new and improved antibodies, vaccines, and recombinant proteins. As progress in biologic development is constrained by currently available methodologies for performing directed evolution, there is a widespread vested interest in more efficient and cost-effective mutagenic methods.

Example 16: Additional Sequences.

*No T7 promoter reporter plasmid (SEQ ID NO: 62)

AC A ATT A ATC ATCGGCTCG A AGCTTGTTG AC A ATT A ATC ATCGGC AT AGT AT ATCGGC AT AGT AT A

ATACGACAAGGTGAGGAACTAAACCACGGGATCGGCCATTGAACAAGATGGATTGCA CGCAGGTT

CTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCG GCTGCTCTG

ATGCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCG ACCTGTCCG

GTGCCCTGAATGAACTGCAGGACGAGGCAGCGCGGCTATCGTGGCTGGCCACGACGG GCGTTCCT

TGCGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGC GAAGTGCC

GGGGCAGGATCTCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGC TGATGCAAT

GCGGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACA TCGCATCGA

GCGAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGA GCATCAGG

GGCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGCGCATGCCCGACGGCGATG ATCTCGTC

GTGACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCT GGATTCATC

GACTGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGT GATATTGCT

GAAGAGCTTGGCGGCGAATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCT CCCGATTCG

CAGCGCATCGCCTTCTATCGCCTTCTTGACGAGTTCTTCTGAGGGGATCAATTCTCT AGAGCTTAAT

TAACGCAGCCTGAATGGCGAATAGGGATCCTTGACAGCTTATCATCGATAAGCTTTA ATGCGGTAG

TTT ATC AC AGTTGCT A ACGC AGTC AGGC ACCGTGT ACG A AT AGTTCG AC A A AG ATCGC ATTGGT A A

TTACGTTACTCGATGCCATGGGGATTGGCCTTATCATGCCAGTCTTGCCAACGTTAT TACGTGAATT

TATTGCTTCGGAAGATATCGCTAACCACTTTGGCGTATTGCTTGCACTTTATGCGTT AATGCAGGTT

ATCTTTGCTCCTTGGCTTGGAAAAATGTCTGACCGATTTGGTCGGCGCCCAGTGCTG TTGTTGTCAT

TAATAGGCGCATCGCTGGATTACTTATTGCTGGCTTTTTCAAGTGCGCTTTGGATGC TGTATTTAGG

CCGTTTGCTTTCAGGGATCACAGGAGCTACTGGGGCTGTCGCGGCATCGGTCATTGC CGATACCAC

CTCAGCTTCTCAACGCGTGAAGTGGTTCGGTTGGTTAGGGGCAAGTTTTGGGCTTGG TTTAATAGC

GGGGCCTATTATTGGTGGTTTTGCAGGAGAGATTTCACCGCATAGTCCCTTTTTTAT CGCTGCGTTG

CTAAATATTGTCACTTTCCTTGTGGTTATGTTTTGGTTCCGTGAAACCAAAAATACA CGTGATAATA

C AG AT ACCG A AGT AGGGGTTG AG ACGC A ATCG A ATTCGGT AT AC ATC ACTTT ATTT AA A ACG ATGC

CCATTTTGTTGATTATTTATTTTTCAGCGCAATTGATAGGCCAAATTCCCGCAACGG TGTGGGTGCT

ATTT ACCG AAAATCGTTTTGGATGGAATAGCATGATGGTTGGCTTTTCATTAGCGGGTCTTGGTCTT

TTACACTCAGTATTCCAAGCCTTTGTGGCAGGAAGAATAGCCACTAAATGGGGCGAA AAAACGGC AGTACTGCTCGGATTTATTGCAGATAGTAGTGCATTTGCCTTTTTAGCGTTTATATCTGA AGGTTGG

TTAGTTTTCCCTGTTTTAATTTTATTGGCTGGTGGTGGGATCGCTTTACCTGCATTA CAGGGAGTGA

TGTCTATCCAAACAAAGAGTCATCAGCAAGGTGCTTTACAGGGATTATTGGTGAGCC TTACCAATG

CAACCGGTGTTATTGGCCCATTACTGTTTGCTGTTATTTATAATCATTCACTACCAA TTTGGGATGG

CTGGATTTGGATTATTGGTTTAGCGTTTTACTGTATTATTATCCTGCTATCGATGAC CTTCATGTTAA

CCCCTCAAGCTCAGGGGAGTAAACAGGAGACAAGTGCTTAGTGATCCAATTCTTGAA GACGAAAG

GGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAG ACGTCAGGTG

GCACTTTTCGGGGAAATGTGCCCGGTTAACGTGCCGGCACGGCCTGGGTAACCAGGT ATTTTGTCC

ACATAACCGTGCGCAAAATGTTGTGGATAAGCAGGACACAGCAGCAATCCACAGCAG GCATACAA

CCGCACACCGAGGTTACTCCGTTCTACAGGTTACGACGACATGTCAATACTTGCCCT TGACAGGCA

TTGATGGAATCGTAGTCTCACGCTGATAGTCTGATCGACAATACAAGTGGGACCGTG GTCCCAGAC

CGATAATCAGACCGACAACACGAGTGGGATCGTGGTCCCAGACTAATAATCAGACCG ACGATACG

AGTGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTGGGACCGTGGT TCCAGACT

AATAATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGA CGATACGA

GTGGGACCATGGTCCCAGACTAATAATCAGACCGACGATACGAGTGGGACCGTGGTC CCAGTCTG

ATTATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGAC GATACGAG

TGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTGGGACCGTGGTCC CAGTCTGA

TTATCAGACCGACGATACAAGTGGAACAGTGGGCCCAGAGAGAATATTCAGGCCAGT TATGCTTT

CTGGCCTGTAACAAAGGACATTAAGTAAAGACAGATAAACGTAGACTAAAACGTGGT CGCATCAG

GGTGCTGGCTTTTCAAGTTCCTTAAGAATGGCCTCAATTTTCTCTATACACTCAGTT GGAACACGAG

ACCTGTCC AGGTT AAGC ACC ATTTT ATCGCCCTT AT AC A AT ACTGTCGCTCC AGG AGC A A ACTG AT

GTCGTGAGCTTAAACTAGTTCTTGATGCAGATGACGTTTTAAGCACAGAAGTTAAAA GAGTGATAA

CTTCTTCAGCTTCAAATATCACCCCAGCTTTTTTCTGCTCATGAAGGTTAGATGCCT GCTGCTTAAG

TAATTCCTCTTTATCTGTAAAGGCTTTTTGAAGTGCATCACCTGACCGGGCAGATAG TTCACCGGG

GTGAGAAAAAAGAGCAACAACTGATTTAGGCAATTTGGCGGTGTTGATACAGCGGGT AATAATCT

TACGTGAAATATTTTCCGCATCAGCCAGCGCAGAAATATTTCCAGCAAATTCATTCT GCAATCGGC

TTGCATAACGCTGACCACGTTCATAAGCACTTGTTGGGCGATAATCGTTACCCAATC TGGATAATG

CAGCCATCTGCTCATCATCCAGCTCGCCAACCAGAACACGATAATCACTTTCGGTAA GTGCAGCAG

CTTTACGACGGCGACTCCCATCGGCAATTTCTATGACACCAGATACTCTTCGACCGA ACGCCGGTG

TCTGTTGACCAGTCAGTAGAAAAGAAGGGATGAGATCATCCAGTGCGTCCTCAGTAA GCAGCTCC

TGGTCACGTTCATTACCTGACCATACCCGAGAGGTCTTCTCAACACTATCACCCCGG AGCACTTCA

AG AGT A A ACTTC AC ATCCCG ACC AC AT AC AGGC A A AGT A ATGGC ATT ACCGCG AGCC ATT ACTCCT

ACGCGCGCAATTAACGAATCCACCATCGGGGCAGCTGGTGTCGATAACGAAGTATCT TCAACCGG

TTGAGTATTGAGCGTATGTTTTGGAATAACAGGCGCACGCTTCATTATCTAATCTCC CAGCGTGGTT

TAATCAGACGATCGAAAATTTCATTGCAGACAGGTTCCCAAATAGAAAGAGCATTTC TCCAGGCA

CCAGTTGAAGAGCGTTGATCAATGGCCTGTTCAAAAACAGTTCTCATCCGGATCTGA CCTTTACCA

ACTTCATCCGTTTCACGTACAACATTTTTTAGAACCATGCTTCCCCAGGCATCCCGA ATTTGCTCCT

CCATCCACGGGG ACTG AG AGCC ATT ACT ATTGCTGT ATTTGGT AAGC A A A AT ACGT AC ATC AGGCT

CGAACCCTTTAAGATCAACGTTCTTGAGCAGATCACGAAGCATATCGAAAAACTGCA GTGCGGAG

GTGTAGTCAAACAACTCAGCAGGCGTGGGAACAATCAGCACATCAGCAGCACATACG ACATTAAT

CGTGCCGATACCCAGGTTAGGCGCGCTGTCAATAACTATGACATCATAGTCATGAGC AACAGTTTC

AATGGCCAGTCGGAGCATCAGGTGTGGATCGGTGGGCAGTTTACCTTCATCAAATTT GCCCATTAA

CTCAGTTTCAATACGGTGCAGAGCCAGACAGGAAGGAATAATGTCAAGCCCCGGCCA GCAAGTGG

GCTTTATTGCATAAGTGACATCGTCCTTTTCCCCAAGATAGAAAGGCAGGAGAGTGT CTTCTGCAT

GAATATGAAGATCTGGTACCCATCCGTGATACATTGAGGCTGTTCCCTGGGGGTCGT TACCTTCCA

CGAGCAAAACACGTAGCCCCTTCAGAGCCAGATCCTGAGCAAGATGAACAGAAACTG AGGTTTTG

TAAACGCCACCTTTATGGGCAGCAACCCCGATCACCGGTGGAAATACGTCTTCAGCA CGTCGCAAT

CGCGTACCAAACACATCACGCATATGATTAATTTGTTCAATTGTATAACCAACACGT TGCTCAACC

CGTCCTCGAATTTCCATATCCGGGTGCGGTAGTCGCCCTGCTTTCTCGGCATCTCTG ATAGCCTGAG

AAGAAACCCCAACTAAATCCGCTGCTTCACCTATTCTCCAGCGCCGGGTTATTTTCC TCGCTTCCGG

GCTGTCATCATTAAACTGTGCAATGGCGATAGCCTTCGTCATTTCATGACCAGCGTT TATGCACTG

GTTAAGTGTTTCCATGAGTTTCATTCTGAACATCCTTTAATCATTGCTTTGCGTTTT TTTATTAAATC

TTGCAATTTACTGCAAAGCAACAACAAAATCGCAAAGTCATCAAAAAACCGCAAAGT TGTTTAAA

AT A AG AGC A AC ACT AC A A A AGG AG AT A AG A AG AGC AC AT ACCTC AGTC ACTTATT ATC ACT AGCG

CTCGCCGCAGCCGTGTAACCGAGCATAGCGAGCGAACTGGCGAGGAAGCAAAGAAGA ACTGTTCT GTCAGATAGCTCTTACGCTCAGCGCAAGAAGAAATATCCACCGTGGGAAAAACTCCAGGT AGAGG

TACACACGCGGATAGCCAATTCAGAGTAATAAACTGTGATAATCAACCCTCATCAAT GATGACGA

ACTAACCCCCGATATCAGGTCACATGACGAAGGGAAAGAGAAGGAAATCAACTGTGA CAAACTGC

CCTCAAATTTGGCTTCCTTAAAAATTACAGTTCAAAAAGTATGAGAAAATCCATGCA GGCTGAAGG

AAACAGCAAAACTGTGACAAATTACCCTCAGTAGGTCAGAACAAATGTGACGAACCA CCCTCAAA

TCTGTGACAGATAACCCTCAGACTATCCTGTCGTCATGGAAGTGATATCGCGGAAGG AAAATACG

ATATGAGTCGTCTGGCGGCCTTTCTTTTTCTCAATGTATGAGAGGCGCATTGGAGTT CTGCTGTTGA

TCTCATTAACACAGACCTGCAGGAAGCGGCGGCGGAAGTCAGGCATACGCTGGTAAC TTTGAGGC

AGCTGGTAACGCTCTATGATCCAGTCGATTTTCAGAGAGACGATGCCTGAGCCATCC GGCTTACGA

TACTGACACAGGGATTCGTATAAACGCATGGCATACGGATTGGTGATTTCTTTTGTT TCACTAAGC

CGAAACTGCGTAAACCGGTTCTGTAACCCGATAAAGAAGGGAATGAGATATGGGTTG ATATGTAC

ACTGTAAAGCCCTCTGGATGGACTGTGCGCACGTTTGATAAACCAAGGAAAAGATTC ATAGCCTTT

TTCATCGCCGGCATCCTCTTCAGGGCGATAAAAAACCACTTCCTTCCCCGCGAAACT CTTCAATGC

CTGCCGT AT ATCCTT ACTGGCTTCCGC AG AGGTC A ATCCG A AT ATTTC AGC AT ATTT AGC A AC ATG

GATCTCGCAGATACCGTCATGTTCCTGTAGGGTGCCATCAGATTTTCTGATCTGGTC AACGAACAG

ATACAGCATACGTTTTTGATCCCGGGAGAGACTATATGCCGCCTCAGTGAGGTCGTT TGACTGGAC

GATTCGCGGGCT ATTTTT ACGTTTCTTGTGATTGATAACCGCTGTTTCCGCCATGACAGATCCATGT

G A AGTGTG AC A AGTTTTT AG ATTGTC AC ACT A A AT A A A A A AG AGTC A AT A AGC AGGG AT A ACTTT

GTGAAAAAACAGCTTCTTCTGAGGGCAATTTGTCACAGGGTTAAGGGCAATTTGTCA CAGACAGG

ACTGTCATTTGAGGGTGATTTGTCACACTGAAAGGGCAATTTGTCACAACACCTTCT CTAGAACCA

GC ATGG AT A A AGGCCT AC A AGGCGCTCT AA A A A AG A AG ATCT A A A A ACT AT A A A A A A A AT A ATT A

TAAAAATATCCCCGTGGATAAGTGGATAACCCCAAGGGAAGTTTTTTCAGGCATCGT GTGTAAGCA

GAATATATAAGTGCTGTTCCCTGGTGCTTCCTCGCTCACTCGAGCTACGGGGTCTGA CGCTCAGTG

GAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCAC CTAGATCCT

TTT AA ATT AA A A ATG A AGTTTT AA ATC A ATCT A A AGT AT AT ATG AGT A A ACTTGGTCTG AC AGTT A

CCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCAT AGTTGCCTGA

CTGCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCT GCAATGATA

CCGCGGGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGA AGGGCCGA

GCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCG GGAAGCTAG

AGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCAT CGTGGTGTC

ACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGT TACATGATC

CCCCATGTTGTGAAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAG TAAGTTGGC

CGCAGTGTTATCACTCATGCTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCC ATCCGTAAGA

TGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGG CGACCGAGT

TGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAA GTGCTCATC

ATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCC AGTTCGATG

TAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCT GGGTGAGCAA

AAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAA TACTCAT

ACTCTTCCTTTTTC A AT ATT ATTG AAGC ATTT ATC AGGGTT ATTGTCTC ATG AGCGG AT AC AT ATTT

GAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTG CCACCTGG

CGGCCGCTTG

*T7 promoter + filler DNA reporter plasmid (SEQ ID NO: 63)

ACG A A AGGGCCTCGTG AT ACGCCT ATTTTT AT AGGTT AATGTC ATG AT A AT A ATGGTTTCTT AG AC

GTCAGGTGGCACTTTTCGGGGAAATGTGCCCGGTTAACGTGCCGGCACGGCCTGGGT AACCAGGT

ATTTTGTCCACATAACCGTGCGCAAAATGTTGTGGATAAGCAGGACACAGCAGCAAT CCACAGCA

GGC AT AC A ACCGC AC ACCG AGGTT ACTCCGTTCT AC AGGTT ACG ACG AC ATGTC A AT ACTTGCCCT

TGACAGGCATTGATGGAATCGTAGTCTCACGCTGATAGTCTGATCGACAATACAAGT GGGACCGT

GGTCCCAGACCGATAATCAGACCGACAACACGAGTGGGATCGTGGTCCCAGACTAAT AATCAGAC

CGACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTG GGACCGTG

GTTCCAGACTAATAATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATA ATCAGACC

GACGATACGAGTGGGACCATGGTCCCAGACTAATAATCAGACCGACGATACGAGTGG GACCGTGG TCCCAGTCTGATTATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCA GACCG

ACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTGGG ACCGTGGT

CCCAGTCTGATTATCAGACCGACGATACAAGTGGAACAGTGGGCCCAGAGAGAATAT TCAGGCCA

GTT ATGCTTTCTGGCCTGT A AC A A AGG AC ATT AAGT A A AG AC AG AT A A ACGT AG ACT A A A ACGTG

GTCGCATCAGGGTGCTGGCTTTTCAAGTTCCTTAAGAATGGCCTCAATTTTCTCTAT ACACTCAGTT

GGAACACGAGACCTGTCCAGGTTAAGCACCATTTTATCGCCCTTATACAATACTGTC GCTCCAGGA

GCAAACTGATGTCGTGAGCTTAAACTAGTTCTTGATGCAGATGACGTTTTAAGCACA GAAGTTAAA

AGAGTGATAACTTCTTCAGCTTCAAATATCACCCCAGCTTTTTTCTGCTCATGAAGG TTAGATGCCT

GCTGCTTAAGTAATTCCTCTTTATCTGTAAAGGCTTTTTGAAGTGCATCACCTGACC GGGCAGATA

GTTCACCGGGGTGAGAAAAAAGAGCAACAACTGATTTAGGCAATTTGGCGGTGTTGA TACAGCGG

GT AAT A ATCTT ACGTG A A AT ATTTTCCGC ATC AGCC AGCGC AG A A AT ATTTCC AGC A A ATTC ATTC

TGCAATCGGCTTGCATAACGCTGACCACGTTCATAAGCACTTGTTGGGCGATAATCG TTACCCAAT

CTGGATAATGCAGCCATCTGCTCATCATCCAGCTCGCCAACCAGAACACGATAATCA CTTTCGGTA

AGTGCAGCAGCTTTACGACGGCGACTCCCATCGGCAATTTCTATGACACCAGATACT CTTCGACCG

AACGCCGGTGTCTGTTGACCAGTCAGTAGAAAAGAAGGGATGAGATCATCCAGTGCG TCCTCAGT

AAGCAGCTCCTGGTCACGTTCATTACCTGACCATACCCGAGAGGTCTTCTCAACACT ATCACCCCG

GAGCACTTCAAGAGTAAACTTCACATCCCGACCACATACAGGCAAAGTAATGGCATT ACCGCGAG

CCATTACTCCTACGCGCGCAATTAACGAATCCACCATCGGGGCAGCTGGTGTCGATA ACGAAGTAT

CTTCAACCGGTTGAGTATTGAGCGTATGTTTTGGAATAACAGGCGCACGCTTCATTA TCTAATCTCC

CAGCGTGGTTTAATCAGACGATCGAAAATTTCATTGCAGACAGGTTCCCAAATAGAA AGAGCATTT

CTCCAGGCACCAGTTGAAGAGCGTTGATCAATGGCCTGTTCAAAAACAGTTCTCATC CGGATCTGA

CCTTTACCAACTTCATCCGTTTCACGTACAACATTTTTTAGAACCATGCTTCCCCAG GCATCCCGAA

TTTGCTCCTCCATCCACGGGGACTGAGAGCCATTACTATTGCTGTATTTGGTAAGCA AAATACGTA

CATCAGGCTCGAACCCTTTAAGATCAACGTTCTTGAGCAGATCACGAAGCATATCGA AAAACTGC

AGTGCGGAGGTGTAGTCAAACAACTCAGCAGGCGTGGGAACAATCAGCACATCAGCA GCACATAC

G AC ATT A ATCGTGCCG AT ACCC AGGTT AGGCGCGCTGTC A AT A ACT ATG AC ATC AT AGTC ATG AGC

AACAGTTTCAATGGCCAGTCGGAGCATCAGGTGTGGATCGGTGGGCAGTTTACCTTC ATCAAATTT

GCCCATTAACTCAGTTTCAATACGGTGCAGAGCCAGACAGGAAGGAATAATGTCAAG CCCCGGCC

AGCAAGTGGGCTTTATTGCATAAGTGACATCGTCCTTTTCCCCAAGATAGAAAGGCA GGAGAGTGT

CTTCTGCATGAATATGAAGATCTGGTACCCATCCGTGATACATTGAGGCTGTTCCCT GGGGGTCGT

TACCTTCCACGAGCAAAACACGTAGCCCCTTCAGAGCCAGATCCTGAGCAAGATGAA CAGAAACT

GAGGTTTTGTAAACGCCACCTTTATGGGCAGCAACCCCGATCACCGGTGGAAATACG TCTTCAGCA

CGTCGCAATCGCGTACCAAACACATCACGCATATGATTAATTTGTTCAATTGTATAA CCAACACGT

TGCTCAACCCGTCCTCGAATTTCCATATCCGGGTGCGGTAGTCGCCCTGCTTTCTCG GCATCTCTGA

T AGCCTG AG A AG A A ACCCC A ACT A A ATCCGCTGCTTC ACCT ATTCTCC AGCGCCGGGTT ATTTTCC

TCGCTTCCGGGCTGTCATCATTAAACTGTGCAATGGCGATAGCCTTCGTCATTTCAT GACCAGCGTT

TATGCACTGGTTAAGTGTTTCCATGAGTTTCATTCTGAACATCCTTTAATCATTGCT TTGCGTTTTTT

TATTAAATCTTGCAATTTACTGCAAAGCAACAACAAAATCGCAAAGTCATCAAAAAA CCGCAAAG

TTGTTT AAA AT A AG AGC A AC ACT AC A A A AGG AG AT A AG A AG AGC AC AT ACCTC AGTC ACTT ATT A

TCACTAGCGCTCGCCGCAGCCGTGTAACCGAGCATAGCGAGCGAACTGGCGAGGAAG CAAAGAA

GAACTGTTCTGTCAGATAGCTCTTACGCTCAGCGCAAGAAGAAATATCCACCGTGGG AAAAACTC

CAGGTAGAGGTACACACGCGGATAGCCAATTCAGAGTAATAAACTGTGATAATCAAC CCTCATCA

ATGATGACGAACTAACCCCCGATATCAGGTCACATGACGAAGGGAAAGAGAAGGAAA TCAACTGT

GACAAACTGCCCTCAAATTTGGCTTCCTTAAAAATTACAGTTCAAAAAGTATGAGAA AATCCATGC

AGGCTGAAGGAAACAGCAAAACTGTGACAAATTACCCTCAGTAGGTCAGAACAAATG TGACGAAC

CACCCTCAAATCTGTGACAGATAACCCTCAGACTATCCTGTCGTCATGGAAGTGATA TCGCGGAAG

GAAAATACGATATGAGTCGTCTGGCGGCCTTTCTTTTTCTCAATGTATGAGAGGCGC ATTGGAGTT

CTGCTGTTGATCTCATTAACACAGACCTGCAGGAAGCGGCGGCGGAAGTCAGGCATA CGCTGGTA

ACTTTGAGGCAGCTGGTAACGCTCTATGATCCAGTCGATTTTCAGAGAGACGATGCC TGAGCCATC

CGGCTTACGATACTGACACAGGGATTCGTATAAACGCATGGCATACGGATTGGTGAT TTCTTTTGT

TTCACTAAGCCGAAACTGCGTAAACCGGTTCTGTAACCCGATAAAGAAGGGAATGAG ATATGGGT

TGATATGTACACTGTAAAGCCCTCTGGATGGACTGTGCGCACGTTTGATAAACCAAG GAAAAGATT

CATAGCCTTTTTCATCGCCGGCATCCTCTTCAGGGCGATAAAAAACCACTTCCTTCC CCGCGAAAC

TCTTCAATGCCTGCCGTATATCCTTACTGGCTTCCGCAGAGGTCAATCCGAATATTT CAGCATATTT

AGCAACATGGATCTCGCAGATACCGTCATGTTCCTGTAGGGTGCCATCAGATTTTCT GATCTGGTC AACGAACAGATACAGCATACGTTTTTGATCCCGGGAGAGACTATATGCCGCCTCAGTGAG GTCGTT

TGACTGGACGATTCGCGGGCTATTTTTACGTTTCTTGTGATTGATAACCGCTGTTTC CGCCATGACA

GATCCATGTGAAGTGTGACAAGTTTTTAGATTGTCACACTAAATAAAAAAGAGTCAA TAAGCAGG

GATAACTTTGTGAAAAAACAGCTTCTTCTGAGGGCAATTTGTCACAGGGTTAAGGGC AATTTGTCA

CAGACAGGACTGTCATTTGAGGGTGATTTGTCACACTGAAAGGGCAATTTGTCACAA CACCTTCTC

TAGAACCAGCATGGATAAAGGCCTACAAGGCGCTCTAAAAAAGAAGATCTAAAAACT ATAAAAA

A A AT A ATT AT AAA A AT ATCCCCGTGG AT A AGTGG AT A ACCCC A AGGG A AGTTTTTTC AGGC ATCGT

GTGTAAGCAGAATATATAAGTGCTGTTCCCTGGTGCTTCCTCGCTCACTCGAGCTAC GGGGTCTGA

CGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAG GATCTTCAC

CT AG ATCCTTTT AA ATT AA A A ATG A AGTTTT AA ATC A ATCT A A AGT AT AT ATG AGT A A ACTTGGTC

TGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCG TTCATCCATA

GTTGCCTGACTGCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGC CCCAGTGCT

GCAATGATACCGCGGGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAG CCAGCCGG

AAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAA TTGTTGCCG

GG A AGCT AG AGT A AGT AGTTCGCC AGTT A AT AGTTTGCGC A ACGTTGTTGCC ATTGCT AC AGGC AT

CGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATC AAGGCGAGT

TACATGATCCCCCATGTTGTGAAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGT TGTCAGAAG

TAAGTTGGCCGCAGTGTTATCACTCATGCTTATGGCAGCACTGCATAATTCTCTTAC TGTCATGCCA

TCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAG TGTATGCGG

CGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGA ACTTTAAA

AGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCT GTTGAGATC

CAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCAC CAGCGTTTCT

GGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGG AAATGTT

GAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTC TCATGAGCGG

AT AC AT ATTTG AATGT ATTT AG A A A A AT A A AC A A AT AGGGGTTCCGCGC AC ATTTCCCCG A A A AGT

GCCACCTGGCGGCCGCCTTTCAGCAAAAAACCCCGCGAGACCCCCGAAGAGGCCCCG CGGGGTTA

TGCTAGGTCGACGGAGCTCGAATTCTAATACGACTCACTATAGGGAGACCCAAGCTG GCTTGACA

ATT A ATC ATCGGCTCG A AGCTTGTTG AC A ATT AATC ATCGGC AT AGT AT ATCGGC AT AGT AT A AT A

CGACAAGGTGAGGAACTAAACCACGGGATCGGCCATTGAACAAGATGGATTGCACGC AGGTTCTC

CGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCGGCT GCTCTGAT

GCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCGAC CTGTCCGGT

GCCCTGAATGAACTGCAGGACGAGGCAGCGCGGCTATCGTGGCTGGCCACGACGGGC GTTCCTTG

CGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGCGA AGTGCCGG

GGCAGGATCTCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTG ATGCAATGC

GGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACATC GCATCGAGC

GAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGAGC ATCAGGGG

CTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGCGCATGCCCGACGGCGATGAT CTCGTCGTG

ACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCTGGA TTCATCGAC

TGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGTGAT ATTGCTGAA

GAGCTTGGCGGCGAATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCC GATTCGCAG

CGC ATCGCCTTCT ATCGCCTTCTTG ACG AGTTCTTCTG AGGGG ATC A ATTCTCT AG AGCTT A ATT A A

CGCAGCCTGAATGGCGAATAGAAGTTTAAACGCTAGATTGGACAATGGCGAGCCTAG TCTCCCAC

GGCGATCTTGCCGCCCTTCTTGGCCTTAATGAGAATCTCGCGGATCTTGCGGGCGTC CAACTTGCC

GGTCAGTCCTTTAGGCACCTCGTCCACGAACACAACACCACCGCGCAGCTTCTTGGC GGTTGTAAC

CTGGCTGGCCACATAGTCCACGATCTCCTTCTCGGTCATGGTTTTACCGTGTTCCAG CACGACGACT

GCGGCGGGCAGCTCGCCGGCATCGTCGTCGGGCAGGCCGGCGACCCCGGCGTCGAAG ATGTTGGG

GTGTTGCAGCAGGATGCTCTCCAGTTCGGCTGGGGCTACCTGGTAGCCCTTGTATTT GATCAGGCT

CTTCAGCCGGTCCACGATGAAGAAGTGCTCGTCCTCGTCCCAGTAGGCGATGTCGCC GCTGTGCAG

CCAGCCGTCCTTGTCGATGAGAGCGTTTGTAGCCTCGGGGTTGTTAACGTAGCCGCT CATGATCAT

GGGGCCACGGACGCACAGCTCGCCGCGCTGGTTCACACCCAGTGTCTTACCGGTGTC CAAGTCCAC

CACCTTAGCCTCGAAGAAGGGCACCACCTTGCCTACTGCGCCAGGCTTGTCGTCCCC TTCGGGGGT

GATCAGAATGGCGCTGGTTGTTTCTGTCAGGCCGTAGCCCTGGCGGATGCCTGGTAG GTGGAAGCG

TTTGGCCACGGCCTCACCTACCTCCTTGCTGAGCGGCGCCCCGCCGCTGGCGATCTC GTGCAAGTT

GCTTAGGTCGTACTTGTCGATGAGAGTGCTCTTAGCGAAGAAGCTAAATAGTGTGGG CACCAGCA

GGGCAGATTGAATCTTATAGTCTTGCAAGCTGCGCAAGAATAGCTCCTCCTCGAAGC GGTACATGA GCACGACCCGAAAGCCGCAGATCAAGTAGCCCAGCGTGGTGAACATGCCGAAGCCGTGGT GAAAT

GGCACCACGCTGAGGATAGCGGTGTCGGGGATGATCTGGTTGCCGAAGATGGGGTCG CGGGCATG

ACTGAATCGGACACAAGCGGTGCGGTGCGGTAGGGCTACGCCCTTGGGCAATCCGGT ACTGCCAC

TACTGTTCATGATCAGGGCGATGGTTTTGTCCCGGTCGAAGCTCTCGGGCACGAAGT CGTACTCGT

TGAAGCCGGGTGGCAAATGGGAAGTCACGAAGGTGTACATGCTTTGGAAGCCCTGGT AGTCGGTC

TTGCTATCCATGATGATGATCTTTTGTATGATCGGTAGCTTCTTTTGCACGTTGAGG ATCTTTTGCA

GCCCTTTCTTGCTCACGAATACGACGGTGGGCTGGCTGATGCCCATGCTGTTCAGCA GCTCGCGCT

CGTTGTAGATGTCGTTAGCTGGGGCCACAGCCACACCGATGAACAGGGCACCCAACA CGGGCATG

AAGAACTGCAAGCTATTCTCGCTGCACACCACGATCCGATGGTTTGTATTCAGCCCA TAGCGCTTC

AT AGCTTCTGCC AGCCG A ACGCTC ATCTCG A AGT ACTCGGCGT AGGT A ATGTCC ACCTCG AT ATGT

GCGTCGGTAAAGGCGATGGTGCCGGGCACCAGGGCGTAGCGCTTCATGGCTTTGTGC AGCTGCTC

GCCGGCGGTCCCGTCTTCGAGTGGGTAGAATGGCGCTGGGCCCTTCTTAATGTTTTT GGCATCTTCC

ATGGTGGTGAATTCCACCACACTGGACTAGTGGATCCTAGGGATGTTTTGGCTCCAT ATGATCACT

ACAAAGACACCAGAACAGGTGTTGTAGTTGGACCAGATTCCAACCGATCCTTGACAG CTTATCATC

GAT A AGCTTT A ATGCGGT AGTTT ATC AC AGTTGCT A ACGC AGTC AGGC ACCGTGT ACG A AT AGTTC

GACAAAGATCGCATTGGTAATTACGTTACTCGATGCCATGGGGATTGGCCTTATCAT GCCAGTCTT

GCCAACGTTATTACGTGAATTTATTGCTTCGGAAGATATCGCTAACCACTTTGGCGT ATTGCTTGCA

CTTTATGCGTTAATGCAGGTTATCTTTGCTCCTTGGCTTGGAAAAATGTCTGACCGA TTTGGTCGGC

GCCCAGTGCTGTTGTTGTCATTAATAGGCGCATCGCTGGATTACTTATTGCTGGCTT TTTCAAGTGC

GCTTTGGATGCTGTATTTAGGCCGTTTGCTTTCAGGGATCACAGGAGCTACTGGGGC TGTCGCGGC

ATCGGTCATTGCCGATACCACCTCAGCTTCTCAACGCGTGAAGTGGTTCGGTTGGTT AGGGGCAAG

TTTTGGGCTTGGTTTAATAGCGGGGCCTATTATTGGTGGTTTTGCAGGAGAGATTTC ACCGCATAGT

CCCTTTTTTATCGCTGCGTTGCTAAATATTGTCACTTTCCTTGTGGTTATGTTTTGG TTCCGTGAAAC

CAAAAATACACGTGATAATACAGATACCGAAGTAGGGGTTGAGACGCAATCGAATTC GGTATACA

TCACTTTATTTAAAACGATGCCCATTTTGTTGATTATTTATTTTTCAGCGCAATTGA TAGGCCAAAT

TCCCGCAACGGTGTGGGTGCTATTTACCGAAAATCGTTTTGGATGGAATAGCATGAT GGTTGGCTT

TTCATTAGCGGGTCTTGGTCTTTTACACTCAGTATTCCAAGCCTTTGTGGCAGGAAG AATAGCCACT

AAATGGGGCGAAAAAACGGCAGTACTGCTCGGATTTATTGCAGATAGTAGTGCATTT GCCTTTTTA

GCGTTTATATCTGAAGGTTGGTTAGTTTTCCCTGTTTTAATTTTATTGGCTGGTGGT GGGATCGCTTT

ACCTGCATTACAGGGAGTGATGTCTATCCAAACAAAGAGTCATCAGCAAGGTGCTTT ACAGGGAT

TATTGGTGAGCCTTACCAATGCAACCGGTGTTATTGGCCCATTACTGTTTGCTGTTA TTTATAATCA

TTCACTACCAATTTGGGATGGCTGGATTTGGATTATTGGTTTAGCGTTTTACTGTAT TATTATCCTG

CTATCGATGACCTTCATGTTAACCCCTCAAGCTCAGGGGAGTAAACAGGAGACAAGT GCTTAGTG

ATCCAATTCTTGAAG

*T7 promoter + terminators reporter plasmid (SEQ ID NO: 64)

ACG A A AGGGCCTCGTG AT ACGCCT ATTTTT AT AGGTT AATGTC ATG AT A AT A ATGGTTTCTT AG AC

GTCAGGTGGCACTTTTCGGGGAAATGTGCCCGGTTAACGTGCCGGCACGGCCTGGGT AACCAGGT

ATTTTGTCCACATAACCGTGCGCAAAATGTTGTGGATAAGCAGGACACAGCAGCAAT CCACAGCA

GGC AT AC A ACCGC AC ACCG AGGTT ACTCCGTTCT AC AGGTT ACG ACG AC ATGTC A AT ACTTGCCCT

TGACAGGCATTGATGGAATCGTAGTCTCACGCTGATAGTCTGATCGACAATACAAGT GGGACCGT

GGTCCCAGACCGATAATCAGACCGACAACACGAGTGGGATCGTGGTCCCAGACTAAT AATCAGAC

CGACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTG GGACCGTG

GTTCCAGACTAATAATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATA ATCAGACC

GACGATACGAGTGGGACCATGGTCCCAGACTAATAATCAGACCGACGATACGAGTGG GACCGTGG

TCCCAGTCTGATTATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATAA TCAGACCG

ACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTGGG ACCGTGGT

CCCAGTCTGATTATCAGACCGACGATACAAGTGGAACAGTGGGCCCAGAGAGAATAT TCAGGCCA

GTT ATGCTTTCTGGCCTGT A AC A A AGG AC ATT AAGT A A AG AC AG AT A A ACGT AG ACT A A A ACGTG

GTCGCATCAGGGTGCTGGCTTTTCAAGTTCCTTAAGAATGGCCTCAATTTTCTCTAT ACACTCAGTT

GGAACACGAGACCTGTCCAGGTTAAGCACCATTTTATCGCCCTTATACAATACTGTC GCTCCAGGA

GCAAACTGATGTCGTGAGCTTAAACTAGTTCTTGATGCAGATGACGTTTTAAGCACA GAAGTTAAA

AGAGTGATAACTTCTTCAGCTTCAAATATCACCCCAGCTTTTTTCTGCTCATGAAGG TTAGATGCCT

GCTGCTTAAGTAATTCCTCTTTATCTGTAAAGGCTTTTTGAAGTGCATCACCTGACC GGGCAGATA GTTCACCGGGGTGAGAAAAAAGAGCAACAACTGATTTAGGCAATTTGGCGGTGTTGATAC AGCGG

GT AAT A ATCTT ACGTG A A AT ATTTTCCGC ATC AGCC AGCGC AG A A AT ATTTCC AGC A A ATTC ATTC

TGCAATCGGCTTGCATAACGCTGACCACGTTCATAAGCACTTGTTGGGCGATAATCG TTACCCAAT

CTGGATAATGCAGCCATCTGCTCATCATCCAGCTCGCCAACCAGAACACGATAATCA CTTTCGGTA

AGTGCAGCAGCTTTACGACGGCGACTCCCATCGGCAATTTCTATGACACCAGATACT CTTCGACCG

AACGCCGGTGTCTGTTGACCAGTCAGTAGAAAAGAAGGGATGAGATCATCCAGTGCG TCCTCAGT

AAGCAGCTCCTGGTCACGTTCATTACCTGACCATACCCGAGAGGTCTTCTCAACACT ATCACCCCG

GAGCACTTCAAGAGTAAACTTCACATCCCGACCACATACAGGCAAAGTAATGGCATT ACCGCGAG

CCATTACTCCTACGCGCGCAATTAACGAATCCACCATCGGGGCAGCTGGTGTCGATA ACGAAGTAT

CTTCAACCGGTTGAGTATTGAGCGTATGTTTTGGAATAACAGGCGCACGCTTCATTA TCTAATCTCC

CAGCGTGGTTTAATCAGACGATCGAAAATTTCATTGCAGACAGGTTCCCAAATAGAA AGAGCATTT

CTCCAGGCACCAGTTGAAGAGCGTTGATCAATGGCCTGTTCAAAAACAGTTCTCATC CGGATCTGA

CCTTTACCAACTTCATCCGTTTCACGTACAACATTTTTTAGAACCATGCTTCCCCAG GCATCCCGAA

TTTGCTCCTCCATCCACGGGGACTGAGAGCCATTACTATTGCTGTATTTGGTAAGCA AAATACGTA

CATCAGGCTCGAACCCTTTAAGATCAACGTTCTTGAGCAGATCACGAAGCATATCGA AAAACTGC

AGTGCGGAGGTGTAGTCAAACAACTCAGCAGGCGTGGGAACAATCAGCACATCAGCA GCACATAC

G AC ATT A ATCGTGCCG AT ACCC AGGTT AGGCGCGCTGTC A AT A ACT ATG AC ATC AT AGTC ATG AGC

AACAGTTTCAATGGCCAGTCGGAGCATCAGGTGTGGATCGGTGGGCAGTTTACCTTC ATCAAATTT

GCCCATTAACTCAGTTTCAATACGGTGCAGAGCCAGACAGGAAGGAATAATGTCAAG CCCCGGCC

AGCAAGTGGGCTTTATTGCATAAGTGACATCGTCCTTTTCCCCAAGATAGAAAGGCA GGAGAGTGT

CTTCTGCATGAATATGAAGATCTGGTACCCATCCGTGATACATTGAGGCTGTTCCCT GGGGGTCGT

TACCTTCCACGAGCAAAACACGTAGCCCCTTCAGAGCCAGATCCTGAGCAAGATGAA CAGAAACT

GAGGTTTTGTAAACGCCACCTTTATGGGCAGCAACCCCGATCACCGGTGGAAATACG TCTTCAGCA

CGTCGCAATCGCGTACCAAACACATCACGCATATGATTAATTTGTTCAATTGTATAA CCAACACGT

TGCTCAACCCGTCCTCGAATTTCCATATCCGGGTGCGGTAGTCGCCCTGCTTTCTCG GCATCTCTGA

T AGCCTG AG A AG A A ACCCC A ACT A A ATCCGCTGCTTC ACCT ATTCTCC AGCGCCGGGTT ATTTTCC

TCGCTTCCGGGCTGTCATCATTAAACTGTGCAATGGCGATAGCCTTCGTCATTTCAT GACCAGCGTT

TATGCACTGGTTAAGTGTTTCCATGAGTTTCATTCTGAACATCCTTTAATCATTGCT TTGCGTTTTTT

TATTAAATCTTGCAATTTACTGCAAAGCAACAACAAAATCGCAAAGTCATCAAAAAA CCGCAAAG

TTGTTT AAA AT A AG AGC A AC ACT AC AAA AGG AG AT A AG A AG AGC AC AT ACCTC AGTC ACTT ATT A

TCACTAGCGCTCGCCGCAGCCGTGTAACCGAGCATAGCGAGCGAACTGGCGAGGAAG CAAAGAA

GAACTGTTCTGTCAGATAGCTCTTACGCTCAGCGCAAGAAGAAATATCCACCGTGGG AAAAACTC

CAGGTAGAGGTACACACGCGGATAGCCAATTCAGAGTAATAAACTGTGATAATCAAC CCTCATCA

ATGATGACGAACTAACCCCCGATATCAGGTCACATGACGAAGGGAAAGAGAAGGAAA TCAACTGT

GACAAACTGCCCTCAAATTTGGCTTCCTTAAAAATTACAGTTCAAAAAGTATGAGAA AATCCATGC

AGGCTGAAGGAAACAGCAAAACTGTGACAAATTACCCTCAGTAGGTCAGAACAAATG TGACGAAC

CACCCTCAAATCTGTGACAGATAACCCTCAGACTATCCTGTCGTCATGGAAGTGATA TCGCGGAAG

GAAAATACGATATGAGTCGTCTGGCGGCCTTTCTTTTTCTCAATGTATGAGAGGCGC ATTGGAGTT

CTGCTGTTGATCTCATTAACACAGACCTGCAGGAAGCGGCGGCGGAAGTCAGGCATA CGCTGGTA

ACTTTGAGGCAGCTGGTAACGCTCTATGATCCAGTCGATTTTCAGAGAGACGATGCC TGAGCCATC

CGGCTTACGATACTGACACAGGGATTCGTATAAACGCATGGCATACGGATTGGTGAT TTCTTTTGT

TTCACTAAGCCGAAACTGCGTAAACCGGTTCTGTAACCCGATAAAGAAGGGAATGAG ATATGGGT

TGATATGTACACTGTAAAGCCCTCTGGATGGACTGTGCGCACGTTTGATAAACCAAG GAAAAGATT

CATAGCCTTTTTCATCGCCGGCATCCTCTTCAGGGCGATAAAAAACCACTTCCTTCC CCGCGAAAC

TCTTCAATGCCTGCCGTATATCCTTACTGGCTTCCGCAGAGGTCAATCCGAATATTT CAGCATATTT

AGCAACATGGATCTCGCAGATACCGTCATGTTCCTGTAGGGTGCCATCAGATTTTCT GATCTGGTC

AACGAACAGATACAGCATACGTTTTTGATCCCGGGAGAGACTATATGCCGCCTCAGT GAGGTCGTT

TGACTGGACGATTCGCGGGCTATTTTTACGTTTCTTGTGATTGATAACCGCTGTTTC CGCCATGACA

GATCCATGTGAAGTGTGACAAGTTTTTAGATTGTCACACTAAATAAAAAAGAGTCAA TAAGCAGG

GATAACTTTGTGAAAAAACAGCTTCTTCTGAGGGCAATTTGTCACAGGGTTAAGGGC AATTTGTCA

CAGACAGGACTGTCATTTGAGGGTGATTTGTCACACTGAAAGGGCAATTTGTCACAA CACCTTCTC

TAGAACCAGCATGGATAAAGGCCTACAAGGCGCTCTAAAAAAGAAGATCTAAAAACT ATAAAAA

A A AT A ATT AT AAA A AT ATCCCCGTGG AT A AGTGG AT A ACCCC A AGGG A AGTTTTTTC AGGC ATCGT

GTGTAAGCAGAATATATAAGTGCTGTTCCCTGGTGCTTCCTCGCTCACTCGAGCTAC GGGGTCTGA

CGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAG GATCTTCAC CT AG ATCCTTTT AA ATT AA A A ATG A AGTTTT AA ATC A ATCT A A AGT AT AT ATG AGT A A ACTTGGTC

TGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCG TTCATCCATA

GTTGCCTGACTGCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGC CCCAGTGCT

GCAATGATACCGCGGGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAG CCAGCCGG

AAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAA TTGTTGCCG

GG A AGCT AG AGT A AGT AGTTCGCC AGTT A AT AGTTTGCGC A ACGTTGTTGCC ATTGCT AC AGGC AT

CGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATC AAGGCGAGT

TACATGATCCCCCATGTTGTGAAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGT TGTCAGAAG

TAAGTTGGCCGCAGTGTTATCACTCATGCTTATGGCAGCACTGCATAATTCTCTTAC TGTCATGCCA

TCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAG TGTATGCGG

CGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGA ACTTTAAA

AGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCT GTTGAGATC

CAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCAC CAGCGTTTCT

GGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGG AAATGTT

GAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTC TCATGAGCGG

AT AC AT ATTTG AATGT ATTT AG A A A A AT A A AC A A AT AGGGGTTCCGCGC AC ATTTCCCCG A A A AGT

GCCACCTGGCGGCCGCCTTTCAGCAAAAAACCCCGCGAGACCCCCGAAGAGGCCCCG CGGGGTTA

TGCTAGGTCGACGGAGCTCGAATTCTAATACGACTCACTATAGGGAGACCCAAGCTG GCTTGACA

ATT A ATC ATCGGCTCG A AGCTTGTTG AC A ATT AATC ATCGGC AT AGT AT ATCGGC AT AGT AT A AT A

CGACAAGGTGAGGAACTAAACCACGGGATCGGCCATTGAACAAGATGGATTGCACGC AGGTTCTC

CGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCGGCT GCTCTGAT

GCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCGAC CTGTCCGGT

GCCCTGAATGAACTGCAGGACGAGGCAGCGCGGCTATCGTGGCTGGCCACGACGGGC GTTCCTTG

CGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGCGA AGTGCCGG

GGCAGGATCTCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTG ATGCAATGC

GGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACATC GCATCGAGC

GAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGAGC ATCAGGGG

CTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGCGCATGCCCGACGGCGATGAT CTCGTCGTG

ACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCTGGA TTCATCGAC

TGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGTGAT ATTGCTGAA

GAGCTTGGCGGCGAATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCC GATTCGCAG

CGC ATCGCCTTCT ATCGCCTTCTTG ACG AGTTCTTCTG AGGGG ATC A ATTCTCT AG AGCTT A ATT A A

CGCAGCCTGAATGGCGAATAGAAGTTTAAACGCTAGACCTAGCATAACCCCGCGGGG CCTCTTCG

GGGGTCTCGCGGGGTTTTTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCT CTTCGGGGG

TCTCGCGGGGTTTTTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTC GGGGGTCTC

GCGGGGTTTTTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGG GTCTCGCGG

GGTTTTTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTCT CGCGGGGTT

TTTTGCTGAAAGGCTAGGAAGTTTAAACGCTAGACCTAGCATAACCCCGCGGGGCCT CTTCGGGGG

TCTCGCGGGGTTTTTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTC GGGGGTCTC

GCGGGGTTTTTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGG GTCTCGCGG

GGTTTTTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTCT CGCGGGGTT

TTTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTCTCGCG GGGTTTTTT

GCTG A A AGGCT AGG AT AT ATTGATCCTTG AC AGCTT ATC ATCG AT A AGCTTT AATGCGGT AGTTT A

TC AC AGTTGCT A ACGC AGTC AGGC ACCGTGT ACG A AT AGTTCG AC A A AG ATCGC ATTGGT A ATT AC

GTTACTCGATGCCATGGGGATTGGCCTTATCATGCCAGTCTTGCCAACGTTATTACG TGAATTTATT

GCTTCGGAAGATATCGCTAACCACTTTGGCGTATTGCTTGCACTTTATGCGTTAATG CAGGTTATCT

TTGCTCCTTGGCTTGGAAAAATGTCTGACCGATTTGGTCGGCGCCCAGTGCTGTTGT TGTCATTAAT

AGGCGCATCGCTGG ATT ACTTATTGCTGGCTTTTTCAAGTGCGCTTTGGATGCTGT ATTT AGGCCGT

TTGCTTTCAGGGATCACAGGAGCTACTGGGGCTGTCGCGGCATCGGTCATTGCCGAT ACCACCTCA

GCTTCTCAACGCGTGAAGTGGTTCGGTTGGTTAGGGGCAAGTTTTGGGCTTGGTTTA ATAGCGGGG

CCTATTATTGGTGGTTTTGCAGGAGAGATTTCACCGCATAGTCCCTTTTTTATCGCT GCGTTGCTAA

ATATTGTCACTTTCCTTGTGGTTATGTTTTGGTTCCGTGAAACCAAAAATACACGTG ATAATACAGA

T ACCG A AGT AGGGGTTGAG ACGC A ATCG A ATTCGGT AT AC ATC ACTTT ATTT A A A ACG ATGCCC AT

TTTGTTGATT ATTT ATTTTTCAGCGCAATTGATAGGCCAAATTCCCGCAACGGTGTGGGTGCT ATTT

ACCGAAAATCGTTTTGGATGGAATAGCATGATGGTTGGCTTTTCATTAGCGGGTCTT GGTCTTTTAC ACTCAGTATTCCAAGCCTTTGTGGCAGGAAGAATAGCCACTAAATGGGGCGAAAAAACGG CAGTA

CTGCTCGGATTTATTGCAGATAGTAGTGCATTTGCCTTTTTAGCGTTTATATCTGAA GGTTGGTTAG

TTTTCCCTGTTTTAATTTTATTGGCTGGTGGTGGGATCGCTTTACCTGCATTACAGG GAGTGATGTC

TATCCAAACAAAGAGTCATCAGCAAGGTGCTTTACAGGGATTATTGGTGAGCCTTAC CAATGCAAC

CGGTGTTATTGGCCCATTACTGTTTGCTGTTATTTATAATCATTCACTACCAATTTG GGATGGCTGG

ATTTGGATTATTGGTTTAGCGTTTTACTGTATTATTATCCTGCTATCGATGACCTTC ATGTTAACCCC

TCAAGCTCAGGGGAGTAAACAGGAGACAAGTGCTTAGTGATCCAATTCTTGAAG

*T7 promoter + antisense T7 promoter reporter plasmid OR * Dual opposing T7 promoters reporter plasmid (SEQ ID NO: 65)

ACG A A AGGGCCTCGTG AT ACGCCT ATTTTT AT AGGTT AATGTC ATG AT A AT A ATGGTTTCTT AG AC

GTCAGGTGGCACTTTTCGGGGAAATGTGCCCGGTTAACGTGCCGGCACGGCCTGGGT AACCAGGT

ATTTTGTCCACATAACCGTGCGCAAAATGTTGTGGATAAGCAGGACACAGCAGCAAT CCACAGCA

GGC AT AC A ACCGC AC ACCG AGGTT ACTCCGTTCT AC AGGTT ACG ACG AC ATGTC A AT ACTTGCCCT

TGACAGGCATTGATGGAATCGTAGTCTCACGCTGATAGTCTGATCGACAATACAAGT GGGACCGT

GGTCCCAGACCGATAATCAGACCGACAACACGAGTGGGATCGTGGTCCCAGACTAAT AATCAGAC

CGACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTG GGACCGTG

GTTCCAGACTAATAATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATA ATCAGACC

GACGATACGAGTGGGACCATGGTCCCAGACTAATAATCAGACCGACGATACGAGTGG GACCGTGG

TCCCAGTCTGATTATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATAA TCAGACCG

ACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTGGG ACCGTGGT

CCCAGTCTGATTATCAGACCGACGATACAAGTGGAACAGTGGGCCCAGAGAGAATAT TCAGGCCA

GTT ATGCTTTCTGGCCTGT A AC A A AGG AC ATT AAGT A A AG AC AG AT A A ACGT AG ACT A A A ACGTG

GTCGCATCAGGGTGCTGGCTTTTCAAGTTCCTTAAGAATGGCCTCAATTTTCTCTAT ACACTCAGTT

GGAACACGAGACCTGTCCAGGTTAAGCACCATTTTATCGCCCTTATACAATACTGTC GCTCCAGGA

GCAAACTGATGTCGTGAGCTTAAACTAGTTCTTGATGCAGATGACGTTTTAAGCACA GAAGTTAAA

AGAGTGATAACTTCTTCAGCTTCAAATATCACCCCAGCTTTTTTCTGCTCATGAAGG TTAGATGCCT

GCTGCTTAAGTAATTCCTCTTTATCTGTAAAGGCTTTTTGAAGTGCATCACCTGACC GGGCAGATA

GTTCACCGGGGTGAGAAAAAAGAGCAACAACTGATTTAGGCAATTTGGCGGTGTTGA TACAGCGG

GT AAT A ATCTT ACGTG A A AT ATTTTCCGC ATC AGCC AGCGC AG A A AT ATTTCC AGC A A ATTC ATTC

TGCAATCGGCTTGCATAACGCTGACCACGTTCATAAGCACTTGTTGGGCGATAATCG TTACCCAAT

CTGGATAATGCAGCCATCTGCTCATCATCCAGCTCGCCAACCAGAACACGATAATCA CTTTCGGTA

AGTGCAGCAGCTTTACGACGGCGACTCCCATCGGCAATTTCTATGACACCAGATACT CTTCGACCG

AACGCCGGTGTCTGTTGACCAGTCAGTAGAAAAGAAGGGATGAGATCATCCAGTGCG TCCTCAGT

AAGCAGCTCCTGGTCACGTTCATTACCTGACCATACCCGAGAGGTCTTCTCAACACT ATCACCCCG

GAGCACTTCAAGAGTAAACTTCACATCCCGACCACATACAGGCAAAGTAATGGCATT ACCGCGAG

CCATTACTCCTACGCGCGCAATTAACGAATCCACCATCGGGGCAGCTGGTGTCGATA ACGAAGTAT

CTTCAACCGGTTGAGTATTGAGCGTATGTTTTGGAATAACAGGCGCACGCTTCATTA TCTAATCTCC

CAGCGTGGTTTAATCAGACGATCGAAAATTTCATTGCAGACAGGTTCCCAAATAGAA AGAGCATTT

CTCCAGGCACCAGTTGAAGAGCGTTGATCAATGGCCTGTTCAAAAACAGTTCTCATC CGGATCTGA

CCTTTACCAACTTCATCCGTTTCACGTACAACATTTTTTAGAACCATGCTTCCCCAG GCATCCCGAA

TTTGCTCCTCCATCCACGGGGACTGAGAGCCATTACTATTGCTGTATTTGGTAAGCA AAATACGTA

CATCAGGCTCGAACCCTTTAAGATCAACGTTCTTGAGCAGATCACGAAGCATATCGA AAAACTGC

AGTGCGGAGGTGTAGTCAAACAACTCAGCAGGCGTGGGAACAATCAGCACATCAGCA GCACATAC

G AC ATT A ATCGTGCCG AT ACCC AGGTT AGGCGCGCTGTC A AT A ACT ATG AC ATC AT AGTC ATG AGC

AACAGTTTCAATGGCCAGTCGGAGCATCAGGTGTGGATCGGTGGGCAGTTTACCTTC ATCAAATTT

GCCCATTAACTCAGTTTCAATACGGTGCAGAGCCAGACAGGAAGGAATAATGTCAAG CCCCGGCC

AGCAAGTGGGCTTTATTGCATAAGTGACATCGTCCTTTTCCCCAAGATAGAAAGGCA GGAGAGTGT

CTTCTGCATGAATATGAAGATCTGGTACCCATCCGTGATACATTGAGGCTGTTCCCT GGGGGTCGT

TACCTTCCACGAGCAAAACACGTAGCCCCTTCAGAGCCAGATCCTGAGCAAGATGAA CAGAAACT

GAGGTTTTGTAAACGCCACCTTTATGGGCAGCAACCCCGATCACCGGTGGAAATACG TCTTCAGCA

CGTCGCAATCGCGTACCAAACACATCACGCATATGATTAATTTGTTCAATTGTATAA CCAACACGT

TGCTCAACCCGTCCTCGAATTTCCATATCCGGGTGCGGTAGTCGCCCTGCTTTCTCG GCATCTCTGA

T AGCCTG AG A AG A A ACCCC A ACT A A ATCCGCTGCTTC ACCT ATTCTCC AGCGCCGGGTT ATTTTCC TCGCTTCCGGGCTGTCATCATTAAACTGTGCAATGGCGATAGCCTTCGTCATTTCATGAC CAGCGTT

TATGCACTGGTTAAGTGTTTCCATGAGTTTCATTCTGAACATCCTTTAATCATTGCT TTGCGTTTTTT

TATTAAATCTTGCAATTTACTGCAAAGCAACAACAAAATCGCAAAGTCATCAAAAAA CCGCAAAG

TTGTTT AAA AT A AG AGC A AC ACT AC AAA AGG AG AT A AG A AG AGC AC AT ACCTC AGTC ACTT ATT A

TCACTAGCGCTCGCCGCAGCCGTGTAACCGAGCATAGCGAGCGAACTGGCGAGGAAG CAAAGAA

GAACTGTTCTGTCAGATAGCTCTTACGCTCAGCGCAAGAAGAAATATCCACCGTGGG AAAAACTC

CAGGTAGAGGTACACACGCGGATAGCCAATTCAGAGTAATAAACTGTGATAATCAAC CCTCATCA

ATGATGACGAACTAACCCCCGATATCAGGTCACATGACGAAGGGAAAGAGAAGGAAA TCAACTGT

GACAAACTGCCCTCAAATTTGGCTTCCTTAAAAATTACAGTTCAAAAAGTATGAGAA AATCCATGC

AGGCTGAAGGAAACAGCAAAACTGTGACAAATTACCCTCAGTAGGTCAGAACAAATG TGACGAAC

CACCCTCAAATCTGTGACAGATAACCCTCAGACTATCCTGTCGTCATGGAAGTGATA TCGCGGAAG

GAAAATACGATATGAGTCGTCTGGCGGCCTTTCTTTTTCTCAATGTATGAGAGGCGC ATTGGAGTT

CTGCTGTTGATCTCATTAACACAGACCTGCAGGAAGCGGCGGCGGAAGTCAGGCATA CGCTGGTA

ACTTTGAGGCAGCTGGTAACGCTCTATGATCCAGTCGATTTTCAGAGAGACGATGCC TGAGCCATC

CGGCTTACGATACTGACACAGGGATTCGTATAAACGCATGGCATACGGATTGGTGAT TTCTTTTGT

TTCACTAAGCCGAAACTGCGTAAACCGGTTCTGTAACCCGATAAAGAAGGGAATGAG ATATGGGT

TGATATGTACACTGTAAAGCCCTCTGGATGGACTGTGCGCACGTTTGATAAACCAAG GAAAAGATT

CATAGCCTTTTTCATCGCCGGCATCCTCTTCAGGGCGATAAAAAACCACTTCCTTCC CCGCGAAAC

TCTTCAATGCCTGCCGTATATCCTTACTGGCTTCCGCAGAGGTCAATCCGAATATTT CAGCATATTT

AGCAACATGGATCTCGCAGATACCGTCATGTTCCTGTAGGGTGCCATCAGATTTTCT GATCTGGTC

AACGAACAGATACAGCATACGTTTTTGATCCCGGGAGAGACTATATGCCGCCTCAGT GAGGTCGTT

TGACTGGACGATTCGCGGGCTATTTTTACGTTTCTTGTGATTGATAACCGCTGTTTC CGCCATGACA

GATCCATGTGAAGTGTGACAAGTTTTTAGATTGTCACACTAAATAAAAAAGAGTCAA TAAGCAGG

GATAACTTTGTGAAAAAACAGCTTCTTCTGAGGGCAATTTGTCACAGGGTTAAGGGC AATTTGTCA

CAGACAGGACTGTCATTTGAGGGTGATTTGTCACACTGAAAGGGCAATTTGTCACAA CACCTTCTC

TAGAACCAGCATGGATAAAGGCCTACAAGGCGCTCTAAAAAAGAAGATCTAAAAACT ATAAAAA

A A AT A ATT AT AAA A AT ATCCCCGTGG AT A AGTGG AT A ACCCC A AGGG A AGTTTTTTC AGGC ATCGT

GTGTAAGCAGAATATATAAGTGCTGTTCCCTGGTGCTTCCTCGCTCACTCGAGCTAC GGGGTCTGA

CGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAG GATCTTCAC

CT AG ATCCTTTT AA ATT AA A A ATG A AGTTTT AA ATC A ATCT A A AGT AT AT ATG AGT A A ACTTGGTC

TGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCG TTCATCCATA

GTTGCCTGACTGCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGC CCCAGTGCT

GCAATGATACCGCGGGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAG CCAGCCGG

AAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAA TTGTTGCCG

GG A AGCT AG AGT A AGT AGTTCGCC AGTT A AT AGTTTGCGC A ACGTTGTTGCC ATTGCT AC AGGC AT

CGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATC AAGGCGAGT

TACATGATCCCCCATGTTGTGAAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGT TGTCAGAAG

TAAGTTGGCCGCAGTGTTATCACTCATGCTTATGGCAGCACTGCATAATTCTCTTAC TGTCATGCCA

TCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAG TGTATGCGG

CGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGA ACTTTAAA

AGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCT GTTGAGATC

CAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCAC CAGCGTTTCT

GGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGG AAATGTT

GAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTC TCATGAGCGG

AT AC AT ATTTG AATGT ATTT AG A A A A AT A A AC A A AT AGGGGTTCCGCGC AC ATTTCCCCG A A A AGT

GCCACCTGGCGGCCGCCTTTCAGCAAAAAACCCCGCGAGACCCCCGAAGAGGCCCCG CGGGGTTA

TGCTAGGTCGACGGAGCTCGAATTCTAATACGACTCACTATAGGGAGACCCAAGCTG GCTTGACA

ATT A ATC ATCGGCTCG A AGCTTGTTG AC A ATT AATC ATCGGC AT AGT AT ATCGGC AT AGT AT A AT A

CGACAAGGTGAGGAACTAAACCACGGGATCGGCCATTGAACAAGATGGATTGCACGC AGGTTCTC

CGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCGGCT GCTCTGAT

GCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCGAC CTGTCCGGT

GCCCTGAATGAACTGCAGGACGAGGCAGCGCGGCTATCGTGGCTGGCCACGACGGGC GTTCCTTG

CGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGCGA AGTGCCGG

GGCAGGATCTCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTG ATGCAATGC

GGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACATC GCATCGAGC GAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGAGCATC AGGGG

CTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGCGCATGCCCGACGGCGATGAT CTCGTCGTG

ACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCTGGA TTCATCGAC

TGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGTGAT ATTGCTGAA

GAGCTTGGCGGCGAATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCC GATTCGCAG

CGC ATCGCCTTCT ATCGCCTTCTTG ACG AGTTCTTCTG AGGGG ATC A ATTCTCT AG AGCTT A ATT A A

CGCAGCCTGAATGGCGAATAGAAGTTTAAACGCTAGCCAGCTTGGGTCTCCCTATAG TGAGTCGTA

TTATCGAGCTCCGTCGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTCTCGCGG GGTTTTTTG

CTGAAAGGGATCCAATTCTTGAAG

*R6K-kan-ccdB (SEQ ID NO: 66)

CCTCCC AC AC AT A ACC AGG AGGTC AG ATT ATGC AGTTT AAGGTTT AC ACCT AT A A A AG AG AG AGC

CGTTATCGTCTGTTTGTGGATGTACAGAGTGATATTATTGACACGCCCGGGCGACGG ATGGTGATC

CCCCTGGCCAGTGCACGTCTGCTGTCAGATAAAGTCTCCCGTGAACTTTACCCGGTG GTGCATATC

GGGGATGAAAGCTGGCGCATGATGACCACCGATATGGCCAGTGTGCCGGTCTCCGTT ATCGGGGA

AGAAGTGGCTGATCTCAGCCACCGCGAAAATGACATCAAAAACGCCATTAACCTGAT GTTCTGGG

GAATATAACCCAGAAGCTTAGCAAAAGCTAAAACCAGGAGCTATTTAATGGCAACAG TTAACCAG

CTGGTACGCAAACCACGTGCTCGCAAAGTTGCGAAAAGCAACGTGCCTGCGCTGGAA GCATGCCC

GC A A A A ACGTGGCGT ATGT ACTCGTGT AT AT ACT ACC ACTCCT A A A A A ACCG A ACTCCGCGCTGCG

TAAAGTATGCCGTGTTCGTCTGACTAACGGTTTCGAAGTGACTTCCTACATCGGTGG TGAAGGTCA

CAACCTGCAGGAGCACTCCGTGATCCTGATCCGTGGCGGTCGTGTTAAAGACCTCCC GGGTGTTCG

TTACCACACCGTACGTGGTGCGCTTGACTGCTCCGGCGTTAAAGACCGTAAGCAGGC TCGTTCCAA

GTATGGCGTGAAGCGTCCTAAGGCTTAATGGTTCGCCCGCCTAATGAGCGGGCTTTT TTTTGAATT

CTTTTTTAATTCGATCTGAAGATCAGCAGTTCAACCTGTTGATAGTACGTACTAAGC TCTCATGTTT

C ACGT ACT A AGCTCTC ATGTTT A ACGT ACT A AGCTCTC ATGTTT AACG A ACT A A ACCCTC ATGGCT

A ACGT ACT A AGCTCTC ATGGCT A ACGT ACT A AGCTCTC ATGTTTC ACGT ACT A AGCTCTC ATGTTTG

A AC A AT A A A ATT A AT AT A A ATC AGC A ACTT AA AT AGCCTCT AAGGTTTT A AGTTTT AT AAG A A A A A

A A AG A AT AT AT A AGGCTTTT A A AGCTTTT AAGGTTT AACGGTTGTGG AC A AC A AGCC AGGG ATGT

AACGCACTGAGAAGCCCTTAGAGCCTCTCAAAGCAATTTTGAGTGACACAGGAACAC TTAACGGC

TGACATGGGATCCCCCTCATCAGTGCCAACATAGTAAGCCAGTATACACTCCGCTAG CGCGGCCGC

CTCG AGTTTCG ACCTGC AGCCTGTTG AC A ATT A ATC ATCGGC AT AGT AT ATCGGC AT AGT AT A AT A

CGACAAGGTGAGGAACTAAACCATGGGATCGGCCATTGAACAAGATGGATTGCACGC AGGTTCTC

CGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCGGCT GCTCTGAT

GCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCGAC CTGTCCGGT

GCCCTGAATGAACTGCAGGACGAGGCAGCGCGGCTATCGTGGCTGGCCACGACGGGC GTTCCTTG

CGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGCGA AGTGCCGG

GGCAGGATCTCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTG ATGCAATGC

GGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACATC GCATCGAGC

GAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGAGC ATCAGGGG

CTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGCGCATGCCCGACGGCGATGAT CTCGTCGTG

ACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCTGGA TTCATCGAC

TGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGTGAT ATTGCTGAA

GAGCTTGGCGGCGAATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCC GATTCGCAG

CGCATCGCCTTCTATCGCCTTCTTGACGAGTTCTTCTGAGGGGATCAATTCTCTAGA GCTCGCTGAT

CAGCCTCGACTGTACCGTTAGC

*R6K-AmilCP-kan-ccdB (SEQ ID NO: 67)

C AC AT A ACC AGG AGGTC AG ATT ATGC AGTTT AAGGTTT AC ACCT AT A A A AG AG AG AGCCGTT ATC

GTCTGTTTGTGGATGTACAGAGTGATATTATTGACACGCCCGGGCGACGGATGGTGA TCCCCCTGG

CCAGTGCACGTCTGCTGTCAGATAAAGTCTCCCGTGAACTTTACCCGGTGGTGCATA TCGGGGATG

AAAGCTGGCGCATGATGACCACCGATATGGCCAGTGTGCCGGTCTCCGTTATCGGGG AAGAAGTG

GCTGATCTCAGCCACCGCGAAAATGACATCAAAAACGCCATTAACCTGATGTTCTGG GGAATATA

ACCCAGAAGCTTAGCAAAAGCTAAAACCAGGAGCTATTTAATGGCAACAGTTAACCA GCTGGTAC

GCAAACCACGTGCTCGCAAAGTTGCGAAAAGCAACGTGCCTGCGCTGGAAGCATGCC CGCAAAAA CGTGGCGT ATGT ACTCGTGT AT AT ACT ACC ACTCCT A A A A A ACCG A ACTCCGCGCTGCGT A A AGT A

TGCCGTGTTCGTCTGACTAACGGTTTCGAAGTGACTTCCTACATCGGTGGTGAAGGT CACAACCTG

CAGGAGCACTCCGTGATCCTGATCCGTGGCGGTCGTGTTAAAGACCTCCCGGGTGTT CGTTACCAC

ACCGTACGTGGTGCGCTTGACTGCTCCGGCGTTAAAGACCGTAAGCAGGCTCGTTCC AAGTATGGC

GTGAAGCGTCCTAAGGCTTAATGGTTCGCCCGCCTAATGAGCGGGCTTTTTTTTGAA TTCTTTTTTA

ATTCGATCTGAAGATCAGCAGTTCAACCTGTTGATAGTACGTACTAAGCTCTCATGT TTCACGTACT

A AGCTCTC ATGTTT A ACGT ACT A AGCTCTC ATGTTT A ACG A ACT A A ACCCTC ATGGCT AACGT ACT

AAGCTCTCATGGCTAACGTACTAAGCTCTCATGTTTCACGTACTAAGCTCTCATGTT TGAACAATA

A A ATT A AT AT A A ATC AGC A ACTT A A AT AGCCTCT A AGGTTTT A AGTTTT AT A AG A A A A A A A AG A AT

AT AT A AGGCTTTT A A AGCTTTT A AGGTTT AACGGTTGTGG AC A AC A AGCC AGGG ATGT A ACGC ACT

GAGAAGCCCTTAGAGCCTCTCAAAGCAATTTTGAGTGACACAGGAACACTTAACGGC TGACATGG

GATCCGAATTAAAAAAGAATTCAAAAAAAAGCCCGCTCATTAGGCGGGCGAACCAAC CGGTTTAG

GCGACCACAGGTTTGCGTGCAATGGAAATTTCACACTGCTCAACCGAAGTGTAATCC TTGTTGTGA

TTGGTTACATCCAGTTTGCGGTCAACATAGTGATACCCTGGCATCTTCACAGGCTTC TTTGCCTTGT

A AGT AGTTTT A A ATTC AC AC A A AT AGTG ACCGCCTCCTTCT A ACTTC AG AGCC AT A A AGTTGTTTC

CTAGCAGCATTCCATCTCGTGCAAAGAGACGCTCAGTGTTGGGTTCCCAGCCCTGTG TCTTCTTCTG

CATGACAGGTCCATTGGGAGGAAAGTTCAAACCAGAGAACTTGACATGGTAGATGAA ACAGTTGC

CTTGGATGCTGGAATCATTGCTGACAGTACACACTGCACCATCTTCAAAGTTCATGA TCCTCTCCC

ATGTATAGCCCTCCGGGAATGACTGCTTTACATAGTCAGGGATGTCTTCAGGGTACT TGGTGAATG

GTATGCTTCCGTACTGACACTGTGGTGATAAAATATCCCAAGCAAATGGCAGAGGTC CGCCCTTGG

TGACAGTGAGCTTTACCGTCTGCTCCCCCTCGTAGGGCTTACCTTTTCCATCGCCTT CGACCTCAAA

GTAGTGTCCATTGACCGTGCCTGACATATAAACCTTGTAGGTCATTTGTTTAGCGAT CACACTCATC

T AGT ATTTCTCCTCTTT A ATT ACT AG ATCC AC AC ATT AT AGGT AC A A A A AG AC ATT AT ACG AGCCG

GAAGCATAAAGTGTAAAGGTACCCATCAGTGCCAACATAGTAAGCCAGTATACACTC CGCTAGCG

CGGCCGCCTCG AGTTTCG ACCTGC AGCCTGTTG AC A ATT AATC ATCGGC AT AGT AT ATCGGC AT AG

TATAATACGACAAGGTGAGGAACTAAACCATGGGATCGGCCATTGAACAAGATGGAT TGCACGCA

GGTTCTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACA ATCGGCTG

CTCTGATGCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAA GACCGACCT

GTCCGGTGCCCTGAATGAACTGCAGGACGAGGCAGCGCGGCTATCGTGGCTGGCCAC GACGGGCG

TTCCTTGCGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTAT TGGGCGAAG

TGCCGGGGCAGGATCTCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCA TGGCTGATG

CAATGCGGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGA AACATCGCA

TCGAGCGAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACG AAGAGCAT

CAGGGGCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGCGCATGCCCGACGGC GATGATCT

CGTCGTGACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGCTT TTCTGGATT

CATCGACTGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTAC CCGTGATAT

TGCTGAAGAGCTTGGCGGCGAATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGC CGCTCCCGA

TTCGCAGCGCATCGCCTTCTATCGCCTTCTTGACGAGTTCTTCTGAGGGGATCAATT CTCTAGAGCT

CGCTGATCAGCCTCGACTGTACCGTTAGCCCTCCCA

*R6K-kan-ccdB-AmilCP (SEQ ID NO: 68)

C AC AT A ACC AGG AGGTC AG ATT ATGC AGTTT A AGGTTT AC ACCT AT A A A AG AG AG AGCCGTT ATC

GTCTGTTTGTGGATGTACAGAGTGATATTATTGACACGCCCGGGCGACGGATGGTGA TCCCCCTGG

CCAGTGCACGTCTGCTGTCAGATAAAGTCTCCCGTGAACTTTACCCGGTGGTGCATA TCGGGGATG

AAAGCTGGCGCATGATGACCACCGATATGGCCAGTGTGCCGGTCTCCGTTATCGGGG AAGAAGTG

GCTGATCTCAGCCACCGCGAAAATGACATCAAAAACGCCATTAACCTGATGTTCTGG GGAATATA

ACCC AG A AGCTT AGC A A A AGCT A A A ACC AGG AGCT ATTT AGGT ACCTTT AC ACTTT ATGCTTCCGG

CTCGT AT A ATGTCTTTTTGT ACCT AT A ATGTGTGG ATCT AGT A ATT A A AG AGG AG A A AT ACT AG AT

GAGTGTGATCGCTAAACAAATGACCTACAAGGTTTATATGTCAGGCACGGTCAATGG ACACTACTT

TGAGGTCGAAGGCGATGGAAAAGGTAAGCCCTACGAGGGGGAGCAGACGGTAAAGCT CACTGTC

ACCAAGGGCGGACCTCTGCCATTTGCTTGGGATATTTTATCACCACAGTGTCAGTAC GGAAGCATA

CC ATTC ACC A AGT ACCCTG A AG AC ATCCCTG ACT ATGT AA AGC AGTC ATTCCCGG AGGGCT AT AC A

TGGGAGAGGATCATGAACTTTGAAGATGGTGCAGTGTGTACTGTCAGCAATGATTCC AGCATCCA

AGGCAACTGTTTCATCTACCATGTCAAGTTCTCTGGTTTGAACTTTCCTCCCAATGG ACCTGTCATG CAGAAGAAGACACAGGGCTGGGAACCCAACACTGAGCGTCTCTTTGCACGAGATGGAATG CTGCT

AGGAAACAACTTTATGGCTCTGAAGTTAGAAGGAGGCGGTCACTATTTGTGTGAATT TAAAACTAC

TTACAAGGCAAAGAAGCCTGTGAAGATGCCAGGGTATCACTATGTTGACCGCAAACT GGATGTAA

CCAATCACAACAAGGATTACACTTCGGTTGAGCAGTGTGAAATTTCCATTGCACGCA AACCTGTGG

TCGCCTAAACCGGTTGGTTCGCCCGCCTAATGAGCGGGCTTTTTTTTGAATTCTTTT TTAATTCGAT

CTGA AG ATC AGC AGTTC A ACCTGTTG AT AGT ACGT ACT A AGCTCTC ATGTTTC ACGT ACT A AGCTC

TC ATGTTT AACGT ACT A AGCTCTC ATGTTT A ACG A ACT A A ACCCTC ATGGCT A ACGT ACT A AGCTCT

C ATGGCT A ACGT ACT A AGCTCTC ATGTTTC ACGT ACT A AGCTCTC ATGTTTG AAC A AT A A A ATT A A

T AT A A ATC AGC A ACTT AA AT AGCCTCT AAGGTTTT A AGTTTT AT AAG A A A A A A A AG A AT AT AT A AG

GCTTTTAAAGCTTTTAAGGTTTAACGGTTGTGGACAACAAGCCAGGGATGTAACGCA CTGAGAAG

CCCTTAGAGCCTCTCAAAGCAATTTTGAGTGACACAGGAACACTTAACGGCTGACAT GGGATCCCC

CTCATCAGTGCCAACATAGTAAGCCAGTATACACTCCGCTAGCGCGGCCGCCTCGAG TTTCGACCT

GCAGCCTGTTGACAATTAATCATCGGCATAGTATATCGGCATAGTATAATACGACAA GGTGAGGA

ACTAAACCATGGGATCGGCCATTGAACAAGATGGATTGCACGCAGGTTCTCCGGCCG CTTGGGTG

GAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCGGCTGCTCTGATGCCGCC GTGTTCCGG

CTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCGACCTGTCCGGTGCCCTG AATGAACTG

CAGGACGAGGCAGCGCGGCTATCGTGGCTGGCCACGACGGGCGTTCCTTGCGCAGCT GTGCTCGA

CGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGCGAAGTGCCGGGGCAGGA TCTCCTGT

CATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGCTGATGCAATGCGGCGGC TGCATACGC

TTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACATCGCATCGAGCGAGCAC GTACTCGG

ATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGAGCATCAGGGGCTCGCG CCAGCCGA

ACTGTTCGCCAGGCTCAAGGCGCGCATGCCCGACGGCGATGATCTCGTCGTGACCCA TGGCGATGC

CTGCTTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCTGGATTCATCGACTGTGG CCGGCTGGG

TGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGTGATATTGCTGAAGAGCT TGGCGGCG

AATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCTCCCGATTCGCAGCGCA TCGCCTTCTA

TCGCCTTCTTGACGAGTTCTTCTGAGGGGATCAATTCTCTAGAGCTCGCTGATCAGC CTCGACTGTA

CCGTT AGCCCTCCC A

*BBa_J23 l l4 lacO MutaT7 (SEQ ID NO: 69)

ATT A ACTGGCG A ACT ACTT ACTCT AGCTTCCCGGC A AC A ATT A AT AG ACTGG ATGG AGGCGG AT A A

AGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAA ATCTGGAGC

CGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTC CCGTATCGT

AGTTATCTACACGACGGGGAGTCAGGCAACTATGATGAACGAAATAGACAGATCGCT GAGATAGG

TGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTA GATTGATTTA

CGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGAC CGCTACAC

TTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGT TCGCCGGCTTT

CCCCGTC A AGCTCT A A ATCGGGGGCTCCCTTT AGGGTTCCG ATTT AGTGCTTT ACGGC ACCTCG AC

CCCAAAAAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACG GTTTTTCGC

CCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTTGAACA ACACTCAACC

CTATCTCGGGCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCATTGGTT AAAAAATGAG

CTGATTT A AC A A A A ATTTA ACGCG A ATTTT AAC A A A AT ATT A ACGTTT AC A ATTT A A A AGG ATCT A

GGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTT CCACTGAGCG

TCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTA ATCTGCTGCT

TGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTAC CAACTCTTT

TTCCG A AGGT A ACTGGCTTC AGC AG AGCGC AG AT ACC A A AT ACTGTCCTTCT AGTGT AGCCGT AGT

T AGGCC ACC ACTTC A AG A ACTCTGT AGC ACCGCCT AC AT ACCTCGCTCTGCT A ATCCTGTT ACC AG

TCAGGCATTTGAGAAGCACACGGTCACACTGCTTCCGGTAGTCAATAAACCGGTAAA CCAGCAAT

AGACATAAGCGGCTATTTAACGACCCTGCCCTGAACCGACGACCGGGTCGAATTTGC TTTCGAATT

TCTGCC ATTC ATCCGCTT ATT ATC ACTT ATTC AGGCGT AGC ACC AGGCGTTT A AGGGC ACC A AT A A

CTGCCTTAAAAAAATTACGCCCCGCCCTGCCACTCATCGCAGTACTGTTGTAATTCA TTAAGCATTC

TGCCGACATGGAAGCCATCACAGACGGCATGATGAACCTGAATCGCCAGCGGCATCA GCACCTTG

TCGCCTTGCGTATAATATTTGCCCATGGTGAAAACGGGGGCGAAGAAGTTGTCCATA TTGGCCACG

TTTAAATCAAAACTGGTGAAACTCACCCAGGGATTGGCTGAGACGAAAAACATATTC TCAATAAA

CCCTTTAGGGAAATAGGCCAGGTTTTCACCGTAACACGCCACATCTTGCGAATATAT GTGTAGAAA CTGCCGGAAATCGTCGTGGTATTCACTCCAGAGCGATGAAAACGTTTCAGTTTGCTCATG GAAAAC

GGTGTAACAAGGGTGAACACTATCCCATATCACCAGCTCACCGTCTTTCATTGCCAT ACGGAATTC

CGGATGAGCATTCATCAGGCGGGCAAGAATGTGAATAAAGGCCGGATAAAACTTGTG CTTATTTTT

CTTT ACGGTCTTT A A A A AGGCCGT A AT ATCC AGCTG A ACGGTCTGGTT AT AGGT AC ATTG AGC A AC

TGACTGAAATGCCTCAAAATGTTCTTTACGATGCCATTGGGATATATCAACGGTGGT ATATCCAGT

G ATTTTTTTCTCC ATTTT AGCTTCCTT AGCTCCTG A A A ATCTCG AT A ACTC A A A A A AT ACGCCCGGT

AGTGATCTTATTTCATTATGGTGAAAGTTGGAACCTCTTACGTGCCGATCAACGTCT CATTTTCGCC

AAAAGTTGGCCCAGGGCTTCCCGGTATCAACAGGGACACCAGGATTTATTTATTCTG CGAAGTGAT

CTTCCGTCACAGGTATTTATTCGGCGCAAAGTGCGTCGGGTGATGCTGCCAACTTAC TGATTTAGT

GTATGATGGTGTTTTTGAGGTGCTCCAGTGGCTTCTGTTTCTATCAGCTGTCCCTCC TGTTCAGCTA

CTGACGGGGTGGTGCGTAACGGCAAAAGCACCGCCGGACATCAGCGCTAGCGGAGTG TATACTGG

CTTACTATGTTGGCACTGATGAGGGTGTCAGTGAAGTGCTTCATGTGGCAGGAGAAA AAAGGCTG

CACCGGTGCGTCAGCAGAATATGTGATACAGGATATATTCCGCTTCCTCGCTCACTG ACTCGCTAC

GCTCGGTCGTTCGACTGCGGCGAGCGGAAATGGCTTACGAACGGGGCGGAGATTTCC TGGAAGAT

GCCAGGAAGATACTTAACAGGGAAGTGAGAGGGCCGCGGCAAAGCCGTTTTTCCATA GGCTCCGC

CCCCCTGACAAGCATCACGAAATCTGACGCTCAAATCAGTGGTGGCGAAACCCGACA GGACTATA

AAGATACCAGGCGTTTCCCCCTGGCGGCTCCCTCGTGCGCTCTCCTGTTCCTGCCTT TCGGTTTACC

GGTGTCATTCCGCTGTTATGGCCGCGTTTGTCTCATTCCACGCCTGACACTCAGTTC CGGGTAGGCA

GTTCGCTCCAAGCTGGACTGTATGCACGAACCCCCCGTTCAGTCCGACCGCTGCGCC TTATCCGGT

AACTATCGTCTTGAGTCCAACCCGGAAAGACATGCAAAAGCACCACTGGCAGCAGCC ACTGGTAA

TTGATTTAGAGGAGTTAGTCTTGAAGTCATGCGCCGGTTAAGGCTAAACTGAAAGGA CAAGTTTTG

GTGACTGCGCTCCTCCAAGCCAGTTACCTCGGTTCAAAGAGTTGGTAGCTCAGAGAA CCTTCGAAA

AACCGCCCTGCAAGGCGGTTTTTTCGTTTTCAGAGCAAGAGATTACGCGCAGACCAA AACGATCTC

AAGAAGATCATCTTATTAATCAGATAAAATATTTGCTCATGAGCCCGAAGTGGCGAG CCCGATCTT

CCCCATCGGTGATGTCGGCGATATAGGCGCCAGCAACCGCACCTGTGGCGCCGGTGA TGCCGGCC

ACGATGCGTCCGGCGTAGAGGATCTGCTCATGTTTGACAGCTTATCATCGATGCATA ATGTGCCTG

TCAAATGGACGAATTAATTAAGTAGGTGTTCCACAGGGTAGCCAGCAGCATCCTGCG ATGCAGAT

CCGGAACATAATGGTGCAGGGCGCTGACTTCCGCGTTTCCAGACTTTACGAAACACG GAAACCGA

AGACCATTCATGTTGTTGCTCAGGTCGCAGACGTTTTGCAGCAGCAGTCGCTTCACG TTCGCTCGC

GTATCGGTGATTCATTCTGCTAACCAGTAAGGCAACCCCGCCAGCCTAGCCGGGTCC TCAACGACA

GGAGCACGATCATGCTAGTCATGCCCCGCGCCCACCGGAAGGAGCTGACTGGGTTGA AGGCTCTC

AAGGGCATCGGTCGAGATCCCGGTGCCTAATGAGTGAGCTAACTTACATTAATTGCG TTGCGCTCA

CTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAA CGCGCGGGG

AGAGGCGGTTTGCGTATTGGGCGCCAGGGTGGTTTTTCTTTTCACCAGTGAGACGGG CAACAGCTG

ATTGCCCTTCACCGCCTGGCCCTGAGAGAGTTGCAGCAAGCGGTCCACGCTGGTTTG CCCCAGCAG

GCGAAAATCCTGTTTGATGGTGGTTAACGGCGGGATATAACATGAGCTGTCTTCGGT ATCGTCGTA

TCCCACTACCGAGATGTCCGCACCAACGCGCAGCCCGGACTCGGTAATGGCGCGCAT TGCGCCCA

GCGCCATCTGATCGTTGGCAACCAGCATCGCAGTGGGAACGATGCCCTCATTCAGCA TTTGCATGG

TTTGTTGAAAACCGGACATGGCACTCCAGTCGCCTTCCCGTTCCGCTATCGGCTGAA TTTGATTGCG

AGTGAGATATTTATGCCAGCCAGCCAGACGCAGACGCGCCGAGACAGAACTTAATGG GCCCGCTA

ACAGCGCGATTTGCTGGTGACCCAATGCGACCAGATGCTCCACGCCCAGTCGCGTAC CGTCTTCAT

GGGAGAAAATAATACTGTTGATGGGTGTCTGGTCAGAGACATCAAGAAATAACGCCG GAACATTA

GTGCAGGCAGCTTCCACAGCAATGGCATCCTGGTCATCCAGCGGATAGTTAATGATC AGCCCACTG

ACGCGTTGCGCGAGAAGATTGTGCACCGCCGCTTTACAGGCTTCGACGCCGCTTCGT TCTACCATC

GACACCACCACGCTGGCACCCAGTTGATCGGCGCGAGATTTAATCGCCGCGACAATT TGCGACGG

CGCGTGCAGGGCCAGACTGGAGGTGGCAACGCCAATCAGCAACGACTGTTTGCCCGC CAGTTGTT

GTGCCACGCGGTTGGGAATGTAATTCAGCTCCGCCATCGCCGCTTCCACTTTTTCCC GCGTTTTCGC

AGAAACGTGGCTGGCCTGGTTCACCACGCGGGAAACGGTCTGATAAGAGACACCGGC ATACTCTG

CGACATCGTATAACGTTACTGGTTTCACATTCACCACCCTGAATTGACTCTCTTCCG GGCGCTATCA

TGCCATACCGCGAAAGGTTTTGCGCCATTCGATGGTGTCCGGGATCTCGACGCTCTC CCTTATGCG

ACTCCTGCATTAGGAAGCAGCCCAGTAGTAGGTTGAGGCCGTTGAGCACCGCCGCCG CAAGGAAT

GGTGCATGCAAGGAGATGGCGCCCAACAGTCCCCCGGCCACGGGGCCTGCCACCATA CCCACGCC

GAAACAAGCGCTCATGAGCCCGAAGTGGCGAGCCCGATCTTCCCCATCGGTGATGTC GGCGATAT

AGGCGCCAGCAACCGCACCTGTGGCGCCGGTGATGCCGGCCACGATGCGTCCTCGAG TTTATGGCT

AGCTCAGTCCTAGGTACAATGCTAGCAATTGTGAGCGGATAACAAGGCTAGCGAATT CGAGCTCC CTCT AG A A AT A ATTTTGTTT A ACTTT AAG A AGG AG AT AT ACC ATGGGC AGC AGCC ATC ATC ATC AT

CATCACATGTCTTCTGAAACCGGTCCGGTTGCGGTTGACCCGACCCTGCGTCGTCGT ATCGAACCG

CACGAATTCGAAGTTTTCTTCGACCCGCGTGAACTGCGTAAAGAAACCTGCCTGCTG TACGAAATC

AACTGGGGTGGTCGTCACTCTATCTGGCGTCACACCTCTCAGAACACCAACAAACAC GTTGAAGTT

AACTTCATCGAAAAATTCACCACCGAACGTTACTTCTGCCCGAACACCCGTTGCTCT ATCACCTGG

TTCCTGTCTTGGTCTCCGTGCGGTGAATGCTCTCGTGCGATCACCGAATTCCTGTCT CGTTACCCGC

ACGTTACCCTGTTCATCTACATCGCGCGTCTGTACCACCACGCGGACCCGCGTAACC GTCAGGGTC

TGCGTGACCTGATCTCTTCTGGTGTTACCATCCAGATCATGACCGAACAGGAATCTG GTTACTGCT

GGCGTAACTTCGTTAACTACTCTCCGTCTAACGAAGCGCACTGGCCGCGTTACCCGC ACCTGTGGG

TTCGTCTGTACGTTCTGGAACTGTACTGCATCATCCTGGGTCTGCCGCCGTGCCTGA ACATCCTGCG

TCGTAAACAGCCGCAGCTGACCTTCTTCACCATCGCGCTGCAGTCTTGCCACTACCA GCGTCTGCC

GCCGCACATCCTGTGGGCGACCGGTCTGAAAGGCGGTAGCGGAGGGAGTGGCGGTAG CGGAGGG

AGTGGGAGCTCAAGAGGATACCATATGAACACGATTAACATCGCTAAGAACGACTTC TCTGACAT

CGAACTGGCTGCTATCCCGTTCAACACTCTGGCTGACCATTACGGTGAGCGTTTAGC TCGCGAACA

GTTGGCCCTTGAGCATGAGTCTTACGAGATGGGTGAAGCACGCTTCCGCAAGATGTT TGAGCGTCA

ACTTAAAGCTGGTGAGGTTGCGGATAACGCTGCCGCCAAGCCTCTCATCACTACCCT ACTCCCTAA

GATGATTGCACGCATCAACGACTGGTTTGAGGAAGTGAAAGCTAAGCGCGGCAAGCG CCCGACAG

CCTTCCAGTTCCTGCAAGAAATCAAGCCGGAAGCCGTAGCGTACATCACCATTAAGA CCACTCTGG

CTTGCCTAACCAGTGCTGACAATACAACCGTTCAGGCTGTAGCAAGCGCAATCGGTC GGGCCATTG

AGGACGAGGCTCGCTTCGGTCGTATCCGTGACCTTGAAGCTAAGCACTTCAAGAAAA ACGTTGAG

GAACAACTCAACAAGCGCGTAGGGCACGTCTACAAGAAAGCATTTATGCAAGTTGTC GAGGCTGA

CATGCTCTCTAAGGGTCTACTCGGTGGCGAGGCGTGGTCTTCGTGGCATAAGGAAGA CTCTATTCA

TGTAGGAGTACGCTGCATCGAGATGCTCATTGAGTCAACCGGAATGGTTAGCTTACA CCGCCAAA

ATGCTGGCGTAGTAGGTCAAGACTCTGAGACTATCGAACTCGCACCTGAATACGCTG AGGCTATCG

CAACCCGTGCAGGTGCGCTGGCTGGCATCTCTCCGATGTTCCAACCTTGCGTAGTTC CTCCTAAGC

CGTGGACTGGCATTACTGGTGGTGGCTATTGGGCTAACGGTCGTCGTCCTCTGGCGC TGGTGCGTA

CTCACAGTAAGAAAGCACTGATGCGCTACGAAGACGTTTACATGCCTGAGGTGTACA AAGCGATT

AACATTGCGCAAAACACCGCATGGAAAATCAACAAGAAAGTCCTAGCGGTCGCCAAC GTAATCAC

CAAGTGGAAGCATTGTCCGGTCGAGGACATCCCTGCGATTGAGCGTGAAGAACTCCC GATGAAAC

CGGAAGACATCGACATGAATCCTGAGGCTCTCACCGCGTGGAAACGTGCTGCCGCTG CTGTGTACC

GCAAGGACAAGGCTCGCAAGTCTCGCCGTATCAGCCTTGAGTTCATGCTTGAGCAAG CCAATAAG

TTTGCTAACCATAAGGCCATCTGGTTCCCTTACAACATGGACTGGCGCGGTCGTGTT TACGCTGTGT

CAATGTTCAACCCGCAAGGTAACGATATGACCAAAGGACTGCTTACGCTGGCGAAAG GTAAACCA

ATCGGTAAGGAAGGTTACTACTGGCTGAAAATCCACGGTGCAAACTGTGCGGGTGTC GATAAGGT

TCCGTTCCCTGAGCGCATCAAGTTCATTGAGGAAAACCACGAGAACATCATGGCTTG CGCTAAGTC

TCCACTGGAGAACACTTGGTGGGCTGAGCAAGATTCTCCGTTCTGCTTCCTTGCGTT CTGCTTTGAG

TACGCTGGGGTACAGCACCACGGCCTGAGCTATAACTGCTCCCTTCCGCTGGCGTTT GACGGGTCT

TGCTCTGGCATCCAGCACTTCTCCGCGATGCTCCGAGATGAGGTAGGTGGTCGCGCG GTTAACTTG

CTTCCTAGTGAAACCGTTCAGGACATCTACGGGATTGTTGCTAAGAAAGTCAACGAG ATTCTACAA

GCAGACGCAATCAATGGGACCGATAACGAAGTAGTTACCGTGACCGATGAGAACACT GGTGAAAT

CTCTGAGAAAGTCAAGCTGGGCACTAAGGCACTGGCTGGTCAATGGCTGGCTTACGG TGTTACTCG

CAGTGTGACTAAGCGTTCAGTCATGACGCTGGCTTACGGGTCCAAAGAGTTCGGCTT CCGTCAACA

AGTGCTGGAAGATACCATTCAGCCAGCTATTGATTCCGGCAAGGGTCTGATGTTCAC TCAGCCGAA

TCAGGCTGCTGGATACATGGCTAAGCTGATTTGGGAATCTGTGAGCGTGACGGTGGT AGCTGCGGT

TGAAGCAATGAACTGGCTTAAGTCTGCTGCTAAGCTGCTGGCTGCTGAGGTCAAAGA TAAGAAGA

CTGGAGAGATTCTTCGCAAGCGTTGCGCTGTGCATTGGGTAACTCCTGATGGTTTCC CTGTGTGGC

AGGAATACAAGAAGCCTATTCAGACGCGCTTGAACCTGATGTTCCTCGGTCAGTTCC GCTTACAGC

CTACCATTAACACCAACAAAGATAGCGAGATTGATGCACACAAACAGGAGTCTGGTA TCGCTCCT

AACTTTGTACACAGCCAAGACGGTAGCCACCTTCGTAAGACTGTAGTGTGGGCACAC GAGAAGTA

CGGAATCGAATCTTTTGCACTGATTCACGACTCCTTCGGTACCATTCCGGCTGACGC TGCGAACCT

GTTCAAAGCAGTGCGCGAAACTATGGTTGACACATATGAGTCTTGTGATGTACTGGC TGATTTCTA

CGACCAGTTCGCTGACCAGTTGCACGAGTCTCAATTGGACAAAATGCCAGCACTTCC GGCTAAAG

GTAACTTGAACCTCCGTGACATCTTAGAGTCGGACTTCGCGTTCGCGTAATCTAGAG TCGACCTGC

AGGCATGCAAGCTTGGCTGTTTTGGCGGATGAGAGAAGATTTTCAGCCTGATACAGA TTAAATCAG

AACGCAGAAGCGGTCTGATAAAACAGAATTTGCCTGGCGGCAGTAGCGCGGTGGTCC CACCTGAC CCCATGCCGAACTCAGAAGTGAAACGCCGTAGCGCCGATGGTAGTGTGGGGTCTCCCCAT GCGAG

AGTAGGGAACTGCCAGGCATCAAATAAAACGAAAGGCTCAGTCGAAAGACTGGGCCT TTCGTTTT

ATCTGTTGTTTGTCGGTGAACGCTCTCCTGAGTAGGACAAATCCGCCGGGAGCGGAT TTGAACGTT

GCGAAGCAACGGCCCGGAGGGTGGCGGGCAGGACGCCCGCCATAAACTGCCAGGCAT CAAATTA

AGCAGAAGGCCATCCTGACGGATGGCCTTTTTGCGTTTCTACAAACTCTTTTGTTTA TTTTTCTAAA

TACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAAT ATTGAAAAA

GGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCAT TTTGCCTTCC

TGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGG TGCAGCAA

ACT

*BBa_J23 l l4 lacO rApol (SEQ ID NO: 70)

GGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAA GTTGC

AGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGG AGCCGGTGA

GCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTAT CGTAGTTAT

CTACACGACGGGGAGTCAGGCAACTATGATGAACGAAATAGACAGATCGCTGAGATA GGTGCCTC

ACTG ATT AAGC ATTGGT A ACTGTC AG ACC A AGTTT ACTC AT AT AT ACTTT AG ATTG ATTT ACGCGCC

CTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTAC ACTTGCCA

GCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCG GCTTTCCCCGT

C A AGCTCT A A ATCGGGGGCTCCCTTT AGGGTTCCG ATTT AGTGCTTT ACGGC ACCTCG ACCCC A A A

AAACTTGATTTGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTT CGCCCTTTG

ACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTTGAACAACACTC AACCCTATCT

CGGGCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCATTGGTTAAAAAA TGAGCTGATT

T AAC A A A A ATTT AACGCG A ATTTT A AC A A A AT ATT A ACGTTT AC A ATTT A A A AGG ATCT AGGTG A A

GATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTG AGCGTCAGAC

CCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGC TGCTTGCAAA

CAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTC TTTTTCCGA

AGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGT AGTTAGGCC

ACC ACTTC A AG A ACTCTGT AGC ACCGCCT AC AT ACCTCGCTCTGCT A ATCCTGTT ACC AGTC AGGC

ATTTGAGAAGCACACGGTCACACTGCTTCCGGTAGTCAATAAACCGGTAAACCAGCA ATAGACAT

AAGCGGCTATTTAACGACCCTGCCCTGAACCGACGACCGGGTCGAATTTGCTTTCGA ATTTCTGCC

ATTC ATCCGCTT ATT ATC ACTT ATTC AGGCGT AGC ACC AGGCGTTT A AGGGC ACC A AT A ACTGCCT

TAAAAAAATTACGCCCCGCCCTGCCACTCATCGCAGTACTGTTGTAATTCATTAAGC ATTCTGCCG

ACATGGAAGCCATCACAGACGGCATGATGAACCTGAATCGCCAGCGGCATCAGCACC TTGTCGCC

TTGCGTATAATATTTGCCCATGGTGAAAACGGGGGCGAAGAAGTTGTCCATATTGGC CACGTTTAA

ATCAAAACTGGTGAAACTCACCCAGGGATTGGCTGAGACGAAAAACATATTCTCAAT AAACCCTT

TAGGGAAATAGGCCAGGTTTTCACCGTAACACGCCACATCTTGCGAATATATGTGTA GAAACTGCC

GGAAATCGTCGTGGTATTCACTCCAGAGCGATGAAAACGTTTCAGTTTGCTCATGGA AAACGGTGT

AACAAGGGTGAACACTATCCCATATCACCAGCTCACCGTCTTTCATTGCCATACGGA ATTCCGGAT

GAGCATTCATCAGGCGGGCAAGAATGTGAATAAAGGCCGGATAAAACTTGTGCTTAT TTTTCTTTA

CGGTCTTT A A A A AGGCCGT AAT ATCC AGCTG A ACGGTCTGGTT AT AGGT AC ATTG AGC A ACTG ACT

GAAATGCCTCAAAATGTTCTTTACGATGCCATTGGGATATATCAACGGTGGTATATC CAGTGATTT

TTTTCTCC ATTTT AGCTTCCTT AGCTCCTG A A A ATCTCG AT A ACTC A A A A A AT ACGCCCGGT AGTG A

TCTTATTTCATTATGGTGAAAGTTGGAACCTCTTACGTGCCGATCAACGTCTCATTT TCGCCAAAAG

TTGGCCCAGGGCTTCCCGGT ATC AACAGGG ACACCAGGATTT ATTT ATTCTGCGAAGTGATCTTCC

GTCACAGGTATTTATTCGGCGCAAAGTGCGTCGGGTGATGCTGCCAACTTACTGATT TAGTGTATG

ATGGTGTTTTTGAGGTGCTCCAGTGGCTTCTGTTTCTATCAGCTGTCCCTCCTGTTC AGCTACTGAC

GGGGTGGTGCGTAACGGCAAAAGCACCGCCGGACATCAGCGCTAGCGGAGTGTATAC TGGCTTAC

TATGTTGGCACTGATGAGGGTGTCAGTGAAGTGCTTCATGTGGCAGGAGAAAAAAGG CTGCACCG

GTGCGTCAGCAGAATATGTGATACAGGATATATTCCGCTTCCTCGCTCACTGACTCG CTACGCTCG

GTCGTTCGACTGCGGCGAGCGGAAATGGCTTACGAACGGGGCGGAGATTTCCTGGAA GATGCCAG

GAAGAT ACTT AACAGGG AAGTGAGAGGGCCGCGGCAAAGCCGTTTTTCCATAGGCTCCGCCCCCC

TGACAAGCATCACGAAATCTGACGCTCAAATCAGTGGTGGCGAAACCCGACAGGACT ATAAAGAT

ACCAGGCGTTTCCCCCTGGCGGCTCCCTCGTGCGCTCTCCTGTTCCTGCCTTTCGGT TTACCGGTGT

CATTCCGCTGTTATGGCCGCGTTTGTCTCATTCCACGCCTGACACTCAGTTCCGGGT AGGCAGTTCG

CTCCAAGCTGGACTGTATGCACGAACCCCCCGTTCAGTCCGACCGCTGCGCCTTATC CGGTAACTA

TCGTCTTGAGTCCAACCCGGAAAGACATGCAAAAGCACCACTGGCAGCAGCCACTGG TAATTGAT

TTAGAGGAGTTAGTCTTGAAGTCATGCGCCGGTTAAGGCTAAACTGAAAGGACAAGT TTTGGTGA

CTGCGCTCCTCCAAGCCAGTTACCTCGGTTCAAAGAGTTGGTAGCTCAGAGAACCTT CGAAAAACC GCCCTGCAAGGCGGTTTTTTCGTTTTCAGAGCAAGAGATTACGCGCAGACCAAAACGATC TCAAGA

AGATCATCTTATTAATCAGATAAAATATTTGCTCATGAGCCCGAAGTGGCGAGCCCG ATCTTCCCC

ATCGGTGATGTCGGCGATATAGGCGCCAGCAACCGCACCTGTGGCGCCGGTGATGCC GGCCACGA

TGCGTCCGGCGTAGAGGATCTGCTCATGTTTGACAGCTTATCATCGATGCATAATGT GCCTGTCAA

ATGGACGAATTAATTAAGTAGGTGTTCCACAGGGTAGCCAGCAGCATCCTGCGATGC AGATCCGG

AACATAATGGTGCAGGGCGCTGACTTCCGCGTTTCCAGACTTTACGAAACACGGAAA CCGAAGAC

CATTCATGTTGTTGCTCAGGTCGCAGACGTTTTGCAGCAGCAGTCGCTTCACGTTCG CTCGCGTATC

GGTGATTCATTCTGCTAACCAGTAAGGCAACCCCGCCAGCCTAGCCGGGTCCTCAAC GACAGGAG

CACGATCATGCTAGTCATGCCCCGCGCCCACCGGAAGGAGCTGACTGGGTTGAAGGC TCTCAAGG

GCATCGGTCGAGATCCCGGTGCCTAATGAGTGAGCTAACTTACATTAATTGCGTTGC GCTCACTGC

CCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATCGGCCAACGCG CGGGGAGA

GGCGGTTTGCGTATTGGGCGCCAGGGTGGTTTTTCTTTTCACCAGTGAGACGGGCAA CAGCTGATT

GCCCTTCACCGCCTGGCCCTGAGAGAGTTGCAGCAAGCGGTCCACGCTGGTTTGCCC CAGCAGGCG

AAAATCCTGTTTGATGGTGGTTAACGGCGGGATATAACATGAGCTGTCTTCGGTATC GTCGTATCC

CACTACCGAGATGTCCGCACCAACGCGCAGCCCGGACTCGGTAATGGCGCGCATTGC GCCCAGCG

CCATCTGATCGTTGGCAACCAGCATCGCAGTGGGAACGATGCCCTCATTCAGCATTT GCATGGTTT

GTTGAAAACCGGACATGGCACTCCAGTCGCCTTCCCGTTCCGCTATCGGCTGAATTT GATTGCGAG

TGAGATATTTATGCCAGCCAGCCAGACGCAGACGCGCCGAGACAGAACTTAATGGGC CCGCTAAC

AGCGCGATTTGCTGGTGACCCAATGCGACCAGATGCTCCACGCCCAGTCGCGTACCG TCTTCATGG

GAGAAAATAATACTGTTGATGGGTGTCTGGTCAGAGACATCAAGAAATAACGCCGGA ACATTAGT

GCAGGCAGCTTCCACAGCAATGGCATCCTGGTCATCCAGCGGATAGTTAATGATCAG CCCACTGAC

GCGTTGCGCGAGAAGATTGTGCACCGCCGCTTTACAGGCTTCGACGCCGCTTCGTTC TACCATCGA

CACCACCACGCTGGCACCCAGTTGATCGGCGCGAGATTTAATCGCCGCGACAATTTG CGACGGCG

CGTGCAGGGCCAGACTGGAGGTGGCAACGCCAATCAGCAACGACTGTTTGCCCGCCA GTTGTTGT

GCCACGCGGTTGGGAATGTAATTCAGCTCCGCCATCGCCGCTTCCACTTTTTCCCGC GTTTTCGCAG

AAACGTGGCTGGCCTGGTTCACCACGCGGGAAACGGTCTGATAAGAGACACCGGCAT ACTCTGCG

ACATCGTATAACGTTACTGGTTTCACATTCACCACCCTGAATTGACTCTCTTCCGGG CGCTATCATG

CCATACCGCGAAAGGTTTTGCGCCATTCGATGGTGTCCGGGATCTCGACGCTCTCCC TTATGCGAC

TCCTGCATTAGGAAGCAGCCCAGTAGTAGGTTGAGGCCGTTGAGCACCGCCGCCGCA AGGAATGG

TGCATGCAAGGAGATGGCGCCCAACAGTCCCCCGGCCACGGGGCCTGCCACCATACC CACGCCGA

AACAAGCGCTCATGAGCCCGAAGTGGCGAGCCCGATCTTCCCCATCGGTGATGTCGG CGATATAG

GCGCCAGCAACCGCACCTGTGGCGCCGGTGATGCCGGCCACGATGCGTCCTCGAGTT TATGGCTAG

CTCAGTCCTAGGTACAATGCTAGCAATTGTGAGCGGATAACAAGGCTAGCGAATTCG AGCTCCCTC

T AG A A AT A ATTTTGTTT A ACTTT AAG A AGG AG AT AT ACC ATGGGC AGC AGCC ATC ATC ATC ATC AT

CACATGTCTTCTGAAACCGGTCCGGTTGCGGTTGACCCGACCCTGCGTCGTCGTATC GAACCGCAC

GAATTCGAAGTTTTCTTCGACCCGCGTGAACTGCGTAAAGAAACCTGCCTGCTGTAC GAAATCAAC

TGGGGTGGTCGTCACTCTATCTGGCGTCACACCTCTCAGAACACCAACAAACACGTT GAAGTTAAC

TTCATCGAAAAATTCACCACCGAACGTTACTTCTGCCCGAACACCCGTTGCTCTATC ACCTGGTTCC

TGTCTTGGTCTCCGTGCGGTGAATGCTCTCGTGCGATCACCGAATTCCTGTCTCGTT ACCCGCACGT

TACCCTGTTCATCTACATCGCGCGTCTGTACCACCACGCGGACCCGCGTAACCGTCA GGGTCTGCG

TGACCTGATCTCTTCTGGTGTTACCATCCAGATCATGACCGAACAGGAATCTGGTTA CTGCTGGCG

T AACTTCGTT A ACT ACTCTCCGTCT AACG A AGCGC ACTGGCCGCGTT ACCCGC ACCTGTGGGTTCG

TCTGTACGTTCTGGAACTGTACTGCATCATCCTGGGTCTGCCGCCGTGCCTGAACAT CCTGCGTCGT

AAACAGCCGCAGCTGACCTTCTTCACCATCGCGCTGCAGTCTTGCCACTACCAGCGT CTGCCGCCG

CACATCCTGTGGGCGACCGGTCTGAAATAACTCGAGCTGTTTTGGCGGATGAGAGAA GATTTTCAG

CCTGATACAGATTAAATCAGAACGCAGAAGCGGTCTGATAAAACAGAATTTGCCTGG CGGCAGTA

GCGCGGTGGTCCCACCTGACCCCATGCCGAACTCAGAAGTGAAACGCCGTAGCGCCG ATGGTAGT

GTGGGGTCTCCCCATGCGAGAGTAGGGAACTGCCAGGCATCAAATAAAACGAAAGGC TCAGTCGA

AAGACTGGGCCTTTCGTTTTATCTGTTGTTTGTCGGTGAACGCTCTCCTGAGTAGGA CAAATCCGCC

GGGAGCGGATTTGAACGTTGCGAAGCAACGGCCCGGAGGGTGGCGGGCAGGACGCCC GCCATAA

ACTGCCAGGCATCAAATTAAGCAGAAGGCCATCCTGACGGATGGCCTTTTTGCGTTT CTACAAACT

CTTTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACC CTGATAAATG

CTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTT ATTCCCTTTT

TTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAG ATGCTGAAG

ATCAGTTGGGTGCAGCAAACTATTAACT

* T7 promoter + rpsL reporter plasmid (SEQ ID NO: 80) ACG A A AGGGCCTCGTG AT ACGCCT ATTTTT AT AGGTT AATGTC ATG AT A AT A ATGGTTTCTT AG AC

GTCAGGTGGCACTTTTCGGGGAAATGTGCCCGGTTAACGTGCCGGCACGGCCTGGGT AACCAGGT

ATTTTGTCCACATAACCGTGCGCAAAATGTTGTGGATAAGCAGGACACAGCAGCAAT CCACAGCA

GGC AT AC A ACCGC AC ACCG AGGTT ACTCCGTTCT AC AGGTT ACG ACG AC ATGTC A AT ACTTGCCCT

TGACAGGCATTGATGGAATCGTAGTCTCACGCTGATAGTCTGATCGACAATACAAGT GGGACCGT

GGTCCCAGACCGATAATCAGACCGACAACACGAGTGGGATCGTGGTCCCAGACTAAT AATCAGAC

CGACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTG GGACCGTG

GTTCCAGACTAATAATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATA ATCAGACC

GACGATACGAGTGGGACCATGGTCCCAGACTAATAATCAGACCGACGATACGAGTGG GACCGTGG

TCCCAGTCTGATTATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATAA TCAGACCG

ACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTGGG ACCGTGGT

CCCAGTCTGATTATCAGACCGACGATACAAGTGGAACAGTGGGCCCAGAGAGAATAT TCAGGCCA

GTT ATGCTTTCTGGCCTGT A AC A A AGG AC ATT AAGT A A AG AC AG AT A A ACGT AG ACT A A A ACGTG

GTCGCATCAGGGTGCTGGCTTTTCAAGTTCCTTAAGAATGGCCTCAATTTTCTCTAT ACACTCAGTT

GGAACACGAGACCTGTCCAGGTTAAGCACCATTTTATCGCCCTTATACAATACTGTC GCTCCAGGA

GCAAACTGATGTCGTGAGCTTAAACTAGTTCTTGATGCAGATGACGTTTTAAGCACA GAAGTTAAA

AGAGTGATAACTTCTTCAGCTTCAAATATCACCCCAGCTTTTTTCTGCTCATGAAGG TTAGATGCCT

GCTGCTTAAGTAATTCCTCTTTATCTGTAAAGGCTTTTTGAAGTGCATCACCTGACC GGGCAGATA

GTTCACCGGGGTGAGAAAAAAGAGCAACAACTGATTTAGGCAATTTGGCGGTGTTGA TACAGCGG

GT AAT A ATCTT ACGTG A A AT ATTTTCCGC ATC AGCC AGCGC AG A A AT ATTTCC AGC A A ATTC ATTC

TGCAATCGGCTTGCATAACGCTGACCACGTTCATAAGCACTTGTTGGGCGATAATCG TTACCCAAT

CTGGATAATGCAGCCATCTGCTCATCATCCAGCTCGCCAACCAGAACACGATAATCA CTTTCGGTA

AGTGCAGCAGCTTTACGACGGCGACTCCCATCGGCAATTTCTATGACACCAGATACT CTTCGACCG

AACGCCGGTGTCTGTTGACCAGTCAGTAGAAAAGAAGGGATGAGATCATCCAGTGCG TCCTCAGT

AAGCAGCTCCTGGTCACGTTCATTACCTGACCATACCCGAGAGGTCTTCTCAACACT ATCACCCCG

GAGCACTTCAAGAGTAAACTTCACATCCCGACCACATACAGGCAAAGTAATGGCATT ACCGCGAG

CCATTACTCCTACGCGCGCAATTAACGAATCCACCATCGGGGCAGCTGGTGTCGATA ACGAAGTAT

CTTCAACCGGTTGAGTATTGAGCGTATGTTTTGGAATAACAGGCGCACGCTTCATTA TCTAATCTCC

CAGCGTGGTTTAATCAGACGATCGAAAATTTCATTGCAGACAGGTTCCCAAATAGAA AGAGCATTT

CTCCAGGCACCAGTTGAAGAGCGTTGATCAATGGCCTGTTCAAAAACAGTTCTCATC CGGATCTGA

CCTTTACCAACTTCATCCGTTTCACGTACAACATTTTTTAGAACCATGCTTCCCCAG GCATCCCGAA

TTTGCTCCTCCATCCACGGGGACTGAGAGCCATTACTATTGCTGTATTTGGTAAGCA AAATACGTA

CATCAGGCTCGAACCCTTTAAGATCAACGTTCTTGAGCAGATCACGAAGCATATCGA AAAACTGC

AGTGCGGAGGTGTAGTCAAACAACTCAGCAGGCGTGGGAACAATCAGCACATCAGCA GCACATAC

G AC ATT A ATCGTGCCG AT ACCC AGGTT AGGCGCGCTGTC A AT A ACT ATG AC ATC AT AGTC ATG AGC

AACAGTTTCAATGGCCAGTCGGAGCATCAGGTGTGGATCGGTGGGCAGTTTACCTTC ATCAAATTT

GCCCATTAACTCAGTTTCAATACGGTGCAGAGCCAGACAGGAAGGAATAATGTCAAG CCCCGGCC

AGCAAGTGGGCTTTATTGCATAAGTGACATCGTCCTTTTCCCCAAGATAGAAAGGCA GGAGAGTGT

CTTCTGCATGAATATGAAGATCTGGTACCCATCCGTGATACATTGAGGCTGTTCCCT GGGGGTCGT

TACCTTCCACGAGCAAAACACGTAGCCCCTTCAGAGCCAGATCCTGAGCAAGATGAA CAGAAACT

GAGGTTTTGTAAACGCCACCTTTATGGGCAGCAACCCCGATCACCGGTGGAAATACG TCTTCAGCA

CGTCGCAATCGCGTACCAAACACATCACGCATATGATTAATTTGTTCAATTGTATAA CCAACACGT

TGCTCAACCCGTCCTCGAATTTCCATATCCGGGTGCGGTAGTCGCCCTGCTTTCTCG GCATCTCTGA

T AGCCTG AG A AG A A ACCCC A ACT A A ATCCGCTGCTTC ACCT ATTCTCC AGCGCCGGGTT ATTTTCC

TCGCTTCCGGGCTGTCATCATTAAACTGTGCAATGGCGATAGCCTTCGTCATTTCAT GACCAGCGTT

TATGCACTGGTTAAGTGTTTCCATGAGTTTCATTCTGAACATCCTTTAATCATTGCT TTGCGTTTTTT

TATTAAATCTTGCAATTTACTGCAAAGCAACAACAAAATCGCAAAGTCATCAAAAAA CCGCAAAG

TTGTTT AAA AT A AG AGC A AC ACT AC A A A AGG AG AT A AG A AG AGC AC AT ACCTC AGTC ACTT ATT A

TCACTAGCGCTCGCCGCAGCCGTGTAACCGAGCATAGCGAGCGAACTGGCGAGGAAG CAAAGAA

GAACTGTTCTGTCAGATAGCTCTTACGCTCAGCGCAAGAAGAAATATCCACCGTGGG AAAAACTC

CAGGTAGAGGTACACACGCGGATAGCCAATTCAGAGTAATAAACTGTGATAATCAAC CCTCATCA

ATGATGACGAACTAACCCCCGATATCAGGTCACATGACGAAGGGAAAGAGAAGGAAA TCAACTGT

GACAAACTGCCCTCAAATTTGGCTTCCTTAAAAATTACAGTTCAAAAAGTATGAGAA AATCCATGC

AGGCTGAAGGAAACAGCAAAACTGTGACAAATTACCCTCAGTAGGTCAGAACAAATG TGACGAAC

CACCCTCAAATCTGTGACAGATAACCCTCAGACTATCCTGTCGTCATGGAAGTGATA TCGCGGAAG

GAAAATACGATATGAGTCGTCTGGCGGCCTTTCTTTTTCTCAATGTATGAGAGGCGC ATTGGAGTT

CTGCTGTTGATCTCATTAACACAGACCTGCAGGAAGCGGCGGCGGAAGTCAGGCATA CGCTGGTA

ACTTTGAGGCAGCTGGTAACGCTCTATGATCCAGTCGATTTTCAGAGAGACGATGCC TGAGCCATC

CGGCTTACGATACTGACACAGGGATTCGTATAAACGCATGGCATACGGATTGGTGAT TTCTTTTGT TTCACTAAGCCGAAACTGCGTAAACCGGTTCTGTAACCCGATAAAGAAGGGAATGAGATA TGGGT

TGATATGTACACTGTAAAGCCCTCTGGATGGACTGTGCGCACGTTTGATAAACCAAG GAAAAGATT

CATAGCCTTTTTCATCGCCGGCATCCTCTTCAGGGCGATAAAAAACCACTTCCTTCC CCGCGAAAC

TCTTCAATGCCTGCCGTATATCCTTACTGGCTTCCGCAGAGGTCAATCCGAATATTT CAGCATATTT

AGCAACATGGATCTCGCAGATACCGTCATGTTCCTGTAGGGTGCCATCAGATTTTCT GATCTGGTC

AACGAACAGATACAGCATACGTTTTTGATCCCGGGAGAGACTATATGCCGCCTCAGT GAGGTCGTT

TGACTGGACGATTCGCGGGCTATTTTTACGTTTCTTGTGATTGATAACCGCTGTTTC CGCCATGACA

GATCCATGTGAAGTGTGACAAGTTTTTAGATTGTCACACTAAATAAAAAAGAGTCAA TAAGCAGG

GATAACTTTGTGAAAAAACAGCTTCTTCTGAGGGCAATTTGTCACAGGGTTAAGGGC AATTTGTCA

CAGACAGGACTGTCATTTGAGGGTGATTTGTCACACTGAAAGGGCAATTTGTCACAA CACCTTCTC

TAGAACCAGCATGGATAAAGGCCTACAAGGCGCTCTAAAAAAGAAGATCTAAAAACT ATAAAAA

A A AT A ATT AT AAA A AT ATCCCCGTGG AT A AGTGG AT A ACCCC A AGGG A AGTTTTTTC AGGC ATCGT

GTGTAAGCAGAATATATAAGTGCTGTTCCCTGGTGCTTCCTCGCTCACTCGAGCTAC GGGGTCTGA

CGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAG GATCTTCAC

CT AG ATCCTTTT AA ATT AA A A ATG A AGTTTT AA ATC A ATCT A A AGT AT AT ATG AGT A A ACTTGGTC

TGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCG TTCATCCATA

GTTGCCTGACTGCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGC CCCAGTGCT

GCAATGATACCGCGGGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAG CCAGCCGG

AAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAA TTGTTGCCG

GG A AGCT AG AGT A AGT AGTTCGCC AGTT A AT AGTTTGCGC A ACGTTGTTGCC ATTGCT AC AGGC AT

CGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATC AAGGCGAGT

TACATGATCCCCCATGTTGTGAAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGT TGTCAGAAG

TAAGTTGGCCGCAGTGTTATCACTCATGCTTATGGCAGCACTGCATAATTCTCTTAC TGTCATGCCA

TCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAG TGTATGCGG

CGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGA ACTTTAAA

AGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCT GTTGAGATC

CAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCAC CAGCGTTTCT

GGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGG AAATGTT

GAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTC TCATGAGCGG

AT AC AT ATTTG AATGT ATTT AG A A A A AT A A AC A A AT AGGGGTTCCGCGC AC ATTTCCCCG A A A AGT

GCCACCTGGCGGCCGCCTTTCAGCAAAAAACCCCGCGAGACCCCCGAAGAGGCCCCG CGGGGTTA

TGCT AGGTCG ACGG AGCTCG A ATTCT A AT ACG ACTC ACT AT AGGG AG ACCTTG AC A ATT A ATC ATC

GGCTCGTATAATGCCAGAAGCTTAGCAAAAGCTAAAACCAGGAGCTATTTAATGGCA ACAGTTAA

CCAGCTGGTACGCAAACCACGTGCTCGCAAAGTTGCGAAAAGCAACGTGCCTGCGCT GGAAGCAT

GCCCGC A A A A ACGTGGCGT ATGT ACTCGTGT AT AT ACT ACC ACTCCT A A A A A ACCG A ACTCCGCGC

TGCGTAAAGTATGCCGTGTTCGTCTGACTAACGGTTTCGAAGTGACTTCCTACATCG GTGGTGAAG

GTCACAACCTGCAGGAGCACTCCGTGATCCTGATCCGTGGCGGTCGTGTTAAAGACC TCCCGGGTG

TTCGTTACCACACCGTACGTGGTGCGCTTGACTGCTCCGGCGTTAAAGACCGTAAGC AGGCTCGTT

CCAAGTATGGCGTGAAGCGTCCTAAGGCTTAATGGTTTAATTAACGCAGCCTGAATG GCGAATAG

AAGTTTAAACGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTCTCGCGGG GTTTTTTGC

TGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTCTCGCGGGGTTT TTTGCTGAA

AGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTCTCGCGGGGTTTTTTG CTGAAAGGC

TAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTCTCGCGGGGTTTTTTGCTGA AAGGCTAGA

CCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTCTCGCGGGGTTTTTTGCTGAAAGG CTAGGAAGT

TTAAACGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTCTCGCGGGGTTT TTTGCTGAA

AGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTCTCGCGGGGTTTTTTG CTGAAAGGC

TAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTCTCGCGGGGTTTTTTGCTGA AAGGCTAGA

CCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTCTCGCGGGGTTTTTTGCTGAAAGG CTAGACCTA

GCATAACCCCGCGGGGCCTCTTCGGGGGTCTCGCGGGGTTTTTTGCTGAAAGGCTAG GATATATTG

ATCCTTG AC AGCTT ATC ATCG AT A AGCTTT A ATGCGGT AGTTT ATC AC AGTTGCT AACGC AGTC AG

GCACCGTGTACGAATAGTTCGACAAAGATCGCATTGGTAATTACGTTACTCGATGCC ATGGGGATT

GGCCTT ATC ATGCC AGTCTTGCC A ACGTT ATT ACGTG A ATTT ATTGCTTCGG A AG AT ATCGCT A ACC

ACTTTGGCGTATTGCTTGCACTTTATGCGTTAATGCAGGTTATCTTTGCTCCTTGGC TTGGAAAAAT

GTCTGACCGATTTGGTCGGCGCCCAGTGCTGTTGTTGTCATTAATAGGCGCATCGCT GGATTACTTA

TTGCTGGCTTTTTCAAGTGCGCTTTGGATGCTGTATTTAGGCCGTTTGCTTTCAGGG ATCACAGGAG

CTACTGGGGCTGTCGCGGCATCGGTCATTGCCGATACCACCTCAGCTTCTCAACGCG TGAAGTGGT

TCGGTTGGTTAGGGGCAAGTTTTGGGCTTGGTTTAATAGCGGGGCCTATTATTGGTG GTTTTGCAG

GAGAGATTTCACCGCATAGTCCCTTTTTTATCGCTGCGTTGCTAAATATTGTCACTT TCCTTGTGGT

TATGTTTTGGTTCCGTGAAACCAAAAATACACGTGATAATACAGATACCGAAGTAGG GGTTGAGA CGC A ATCG A ATTCGGT AT AC ATC ACTTT ATTT AA A ACG ATGCCC ATTTTGTTG ATT ATTT ATTTTTC

AGCGC AATTGATAGGCCAAATTCCCGCAACGGTGTGGGTGCTATTTACCGAAAATCGTTTTGGAT G

GAATAGCATGATGGTTGGCTTTTCATTAGCGGGTCTTGGTCTTTTACACTCAGTATT CCAAGCCTTT

GTGGCAGGAAGAATAGCCACTAAATGGGGCGAAAAAACGGCAGTACTGCTCGGATTT ATTGCAGA

TAGTAGTGCATTTGCCTTTTTAGCGTTTATATCTGAAGGTTGGTTAGTTTTCCCTGT TTTAATTTTAT

TGGCTGGTGGTGGGATCGCTTTACCTGCATTACAGGGAGTGATGTCTATCCAAACAA AGAGTCATC

AGCAAGGTGCTTTACAGGGATTATTGGTGAGCCTTACCAATGCAACCGGTGTTATTG GCCCATTAC

TGTTTGCTGTTATTTATAATCATTCACTACCAATTTGGGATGGCTGGATTTGGATTA TTGGTTTAGC

GTTTT ACTGT ATT ATT ATCCTGCT ATCG ATG ACCTTCATGTT A ACCCCTC A AGCTC AGGGG AGT AAA

CAGGAGACAAGTGCTTAGTGATCCAATTCTTGAAG

* folA+T7 promoter plasmid (SEQ ID NO: 81)

ACG A A AGGGCCTCGTG AT ACGCCT ATTTTT AT AGGTT AATGTC ATG AT A AT A ATGGTTTCTT AG AC

GTCAGGTGGCACTTTTCGGGGAAATGTGCCCGGTTAACGTGCCGGCACGGCCTGGGT AACCAGGT

ATTTTGTCCACATAACCGTGCGCAAAATGTTGTGGATAAGCAGGACACAGCAGCAAT CCACAGCA

GGC AT AC A ACCGC AC ACCG AGGTT ACTCCGTTCT AC AGGTT ACG ACG AC ATGTC A AT ACTTGCCCT

TGACAGGCATTGATGGAATCGTAGTCTCACGCTGATAGTCTGATCGACAATACAAGT GGGACCGT

GGTCCCAGACCGATAATCAGACCGACAACACGAGTGGGATCGTGGTCCCAGACTAAT AATCAGAC

CGACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTG GGACCGTG

GTTCCAGACTAATAATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATA ATCAGACC

GACGATACGAGTGGGACCATGGTCCCAGACTAATAATCAGACCGACGATACGAGTGG GACCGTGG

TCCCAGTCTGATTATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATAA TCAGACCG

ACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTGGG ACCGTGGT

CCCAGTCTGATTATCAGACCGACGATACAAGTGGAACAGTGGGCCCAGAGAGAATAT TCAGGCCA

GTT ATGCTTTCTGGCCTGT A AC A A AGG AC ATT AAGT A A AG AC AG AT A A ACGT AG ACT A A A ACGTG

GTCGCATCAGGGTGCTGGCTTTTCAAGTTCCTTAAGAATGGCCTCAATTTTCTCTAT ACACTCAGTT

GGAACACGAGACCTGTCCAGGTTAAGCACCATTTTATCGCCCTTATACAATACTGTC GCTCCAGGA

GCAAACTGATGTCGTGAGCTTAAACTAGTTCTTGATGCAGATGACGTTTTAAGCACA GAAGTTAAA

AGAGTGATAACTTCTTCAGCTTCAAATATCACCCCAGCTTTTTTCTGCTCATGAAGG TTAGATGCCT

GCTGCTTAAGTAATTCCTCTTTATCTGTAAAGGCTTTTTGAAGTGCATCACCTGACC GGGCAGATA

GTTCACCGGGGTGAGAAAAAAGAGCAACAACTGATTTAGGCAATTTGGCGGTGTTGA TACAGCGG

GT AAT A ATCTT ACGTG A A AT ATTTTCCGC ATC AGCC AGCGC AG A A AT ATTTCC AGC A A ATTC ATTC

TGCAATCGGCTTGCATAACGCTGACCACGTTCATAAGCACTTGTTGGGCGATAATCG TTACCCAAT

CTGGATAATGCAGCCATCTGCTCATCATCCAGCTCGCCAACCAGAACACGATAATCA CTTTCGGTA

AGTGCAGCAGCTTTACGACGGCGACTCCCATCGGCAATTTCTATGACACCAGATACT CTTCGACCG

AACGCCGGTGTCTGTTGACCAGTCAGTAGAAAAGAAGGGATGAGATCATCCAGTGCG TCCTCAGT

AAGCAGCTCCTGGTCACGTTCATTACCTGACCATACCCGAGAGGTCTTCTCAACACT ATCACCCCG

GAGCACTTCAAGAGTAAACTTCACATCCCGACCACATACAGGCAAAGTAATGGCATT ACCGCGAG

CCATTACTCCTACGCGCGCAATTAACGAATCCACCATCGGGGCAGCTGGTGTCGATA ACGAAGTAT

CTTCAACCGGTTGAGTATTGAGCGTATGTTTTGGAATAACAGGCGCACGCTTCATTA TCTAATCTCC

CAGCGTGGTTTAATCAGACGATCGAAAATTTCATTGCAGACAGGTTCCCAAATAGAA AGAGCATTT

CTCCAGGCACCAGTTGAAGAGCGTTGATCAATGGCCTGTTCAAAAACAGTTCTCATC CGGATCTGA

CCTTTACCAACTTCATCCGTTTCACGTACAACATTTTTTAGAACCATGCTTCCCCAG GCATCCCGAA

TTTGCTCCTCCATCCACGGGGACTGAGAGCCATTACTATTGCTGTATTTGGTAAGCA AAATACGTA

CATCAGGCTCGAACCCTTTAAGATCAACGTTCTTGAGCAGATCACGAAGCATATCGA AAAACTGC

AGTGCGGAGGTGTAGTCAAACAACTCAGCAGGCGTGGGAACAATCAGCACATCAGCA GCACATAC

G AC ATT A ATCGTGCCG AT ACCC AGGTT AGGCGCGCTGTC A AT A ACT ATG AC ATC AT AGTC ATG AGC

AACAGTTTCAATGGCCAGTCGGAGCATCAGGTGTGGATCGGTGGGCAGTTTACCTTC ATCAAATTT

GCCCATTAACTCAGTTTCAATACGGTGCAGAGCCAGACAGGAAGGAATAATGTCAAG CCCCGGCC

AGCAAGTGGGCTTTATTGCATAAGTGACATCGTCCTTTTCCCCAAGATAGAAAGGCA GGAGAGTGT

CTTCTGCATGAATATGAAGATCTGGTACCCATCCGTGATACATTGAGGCTGTTCCCT GGGGGTCGT

TACCTTCCACGAGCAAAACACGTAGCCCCTTCAGAGCCAGATCCTGAGCAAGATGAA CAGAAACT

GAGGTTTTGTAAACGCCACCTTTATGGGCAGCAACCCCGATCACCGGTGGAAATACG TCTTCAGCA

CGTCGCAATCGCGTACCAAACACATCACGCATATGATTAATTTGTTCAATTGTATAA CCAACACGT

TGCTCAACCCGTCCTCGAATTTCCATATCCGGGTGCGGTAGTCGCCCTGCTTTCTCG GCATCTCTGA

T AGCCTG AG A AG A A ACCCC A ACT A A ATCCGCTGCTTC ACCT ATTCTCC AGCGCCGGGTT ATTTTCC

TCGCTTCCGGGCTGTCATCATTAAACTGTGCAATGGCGATAGCCTTCGTCATTTCAT GACCAGCGTT TATGCACTGGTTAAGTGTTTCCATGAGTTTCATTCTGAACATCCTTTAATCATTGCTTTG CGTTTTTT

TATTAAATCTTGCAATTTACTGCAAAGCAACAACAAAATCGCAAAGTCATCAAAAAA CCGCAAAG

TTGTTT AAA AT A AG AGC A AC ACT AC AAA AGG AG AT A AG A AG AGC AC AT ACCTC AGTC ACTT ATT A

TCACTAGCGCTCGCCGCAGCCGTGTAACCGAGCATAGCGAGCGAACTGGCGAGGAAG CAAAGAA

GAACTGTTCTGTCAGATAGCTCTTACGCTCAGCGCAAGAAGAAATATCCACCGTGGG AAAAACTC

CAGGTAGAGGTACACACGCGGATAGCCAATTCAGAGTAATAAACTGTGATAATCAAC CCTCATCA

ATGATGACGAACTAACCCCCGATATCAGGTCACATGACGAAGGGAAAGAGAAGGAAA TCAACTGT

GACAAACTGCCCTCAAATTTGGCTTCCTTAAAAATTACAGTTCAAAAAGTATGAGAA AATCCATGC

AGGCTGAAGGAAACAGCAAAACTGTGACAAATTACCCTCAGTAGGTCAGAACAAATG TGACGAAC

CACCCTCAAATCTGTGACAGATAACCCTCAGACTATCCTGTCGTCATGGAAGTGATA TCGCGGAAG

GAAAATACGATATGAGTCGTCTGGCGGCCTTTCTTTTTCTCAATGTATGAGAGGCGC ATTGGAGTT

CTGCTGTTGATCTCATTAACACAGACCTGCAGGAAGCGGCGGCGGAAGTCAGGCATA CGCTGGTA

ACTTTGAGGCAGCTGGTAACGCTCTATGATCCAGTCGATTTTCAGAGAGACGATGCC TGAGCCATC

CGGCTTACGATACTGACACAGGGATTCGTATAAACGCATGGCATACGGATTGGTGAT TTCTTTTGT

TTCACTAAGCCGAAACTGCGTAAACCGGTTCTGTAACCCGATAAAGAAGGGAATGAG ATATGGGT

TGATATGTACACTGTAAAGCCCTCTGGATGGACTGTGCGCACGTTTGATAAACCAAG GAAAAGATT

CATAGCCTTTTTCATCGCCGGCATCCTCTTCAGGGCGATAAAAAACCACTTCCTTCC CCGCGAAAC

TCTTCAATGCCTGCCGTATATCCTTACTGGCTTCCGCAGAGGTCAATCCGAATATTT CAGCATATTT

AGCAACATGGATCTCGCAGATACCGTCATGTTCCTGTAGGGTGCCATCAGATTTTCT GATCTGGTC

AACGAACAGATACAGCATACGTTTTTGATCCCGGGAGAGACTATATGCCGCCTCAGT GAGGTCGTT

TGACTGGACGATTCGCGGGCTATTTTTACGTTTCTTGTGATTGATAACCGCTGTTTC CGCCATGACA

GATCCATGTGAAGTGTGACAAGTTTTTAGATTGTCACACTAAATAAAAAAGAGTCAA TAAGCAGG

GATAACTTTGTGAAAAAACAGCTTCTTCTGAGGGCAATTTGTCACAGGGTTAAGGGC AATTTGTCA

CAGACAGGACTGTCATTTGAGGGTGATTTGTCACACTGAAAGGGCAATTTGTCACAA CACCTTCTC

TAGAACCAGCATGGATAAAGGCCTACAAGGCGCTCTAAAAAAGAAGATCTAAAAACT ATAAAAA

A A AT A ATT AT AAA A AT ATCCCCGTGG AT A AGTGG AT A ACCCC A AGGG A AGTTTTTTC AGGC ATCGT

GTGTAAGCAGAATATATAAGTGCTGTTCCCTGGTGCTTCCTCGCTCACTCGAGCTAC GGGGTCTGA

CGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAG GATCTTCAC

CT AG ATCCTTTT AA ATT AA A A ATG A AGTTTT AA ATC A ATCT A A AGT AT AT ATG AGT A A ACTTGGTC

TGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCG TTCATCCATA

GTTGCCTGACTGCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGC CCCAGTGCT

GCAATGATACCGCGGGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAG CCAGCCGG

AAGGGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAA TTGTTGCCG

GG A AGCT AG AGT A AGT AGTTCGCC AGTT A AT AGTTTGCGC A ACGTTGTTGCC ATTGCT AC AGGC AT

CGTGGTGTCACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATC AAGGCGAGT

TACATGATCCCCCATGTTGTGAAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGT TGTCAGAAG

TAAGTTGGCCGCAGTGTTATCACTCATGCTTATGGCAGCACTGCATAATTCTCTTAC TGTCATGCCA

TCCGTAAGATGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAG TGTATGCGG

CGACCGAGTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGA ACTTTAAA

AGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCT GTTGAGATC

CAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCAC CAGCGTTTCT

GGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGG AAATGTT

GAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTC TCATGAGCGG

AT AC AT ATTTG AATGT ATTT AG A A A A AT A A AC A A AT AGGGGTTCCGCGC AC ATTTCCCCG A A A AGT

GCCACCTGGCGGCCGCCTTTCAGCAAAAAACCCCGCGAGACCCCCGAAGAGGCCCCG CGGGGTTA

TGCTAGGTCGACGGAGCTCGAATTCTAATACGACTCACTATAGGGGCGTCGCATCCG GCGCTAGCC

GT AA ATTCT AT AC A A A ATT ACCGCCGCTCC AG A ATCTC A A AGC A AT AGCTGTGAG AGTTCTGCGC A

TCAGCATCGTGGAATTCGCTGAATACCGATTCCCAGTCATCCGGCTCGTAATCCGGG AAATGGGTG

TCGCCTTCCACTTCTGCGTCGATATGCGTCAGATACAGTTTTTGCGCTTTTGGCAAG AACTGTTCAT

AAACGCGACCGCCGCCAATCACCATGATTTCTGGTACGTCACCACACGCCGCGATGG CTTCATCCA

CCGACTTCACCCACGTTACGCGATCGTCCGTACCCGGTTGACTGCTGAGGATAATAT TTTTGCGTCC

TGGCAACGGACGACCGATTGATTCCCAGGTATGGCGGCCCATAATCACGGGTTTATT TAAGGTGTT

GCGTTTAAACCAGGCGAGATCGGCAGGCAGGTTCCACGGCATGGCGTTTTCCATGCC GATAACGC

GATCTACCGCTAACGCCGCAATCAGACTGATCATTGAGATTTCCCGATAAAAAAAAT TGTCGCCAC

TATACGTAAAGCGTAAACCGTCGTCGACTGGTGCGAGGATGATGTTGAGGAAAATTT TATATTCTG

CTGGCGAGTCCACGCTCTCTCCCTGGACTCGCCGCATTACAATGAAACAAAAACAAA CAGTTAGCT

GT AA AGTGTG ATTT ACGTC ACTCTTT ATT AGG ATG AGGGTTTCGTTTCCGGTTC ATCCTT A ATT A AC

GCAGCCTGAATGGCGAATAGAAGTTTAAACGCTAGACCTAGCATAACCCCGCGGGGC CTCTTCGG

GGGTCTCGCGGGGTTTTTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTC TTCGGGGGT CTCGCGGGGTTTTTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGG GTCTCG

CGGGGTTTTTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGG TCTCGCGGG

_{GTTTTTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTC TCGCGGGGTTT}

TTTGCTGAAAGGCTAGGAAGTTTAAACGCTAGACCTAGCATAACCCCGCGGGGCCTC TTCGGGGGT

CTCGCGGGGTTTTTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCG GGGGTCTCG

CGGGGTTTTTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGG TCTCGCGGG

_{GTTTTTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTC TCGCGGGGTTT}

TTTGCTGAAAGGCTAGACCTAGCATAACCCCGCGGGGCCTCTTCGGGGGTCTCGCGG GGTTTTTTG

CTGAAAGGCTAGGATATATTGATCCTTGACAGCTTATCATCGATAAGCTTTAATGCG GTAGTTTAT

CACAGTTGCTAACGCAGTCAGGCACCGTGTACGAATAGTTCGACAAAGATCGCATTG GTAATTAC

GTTACTCGATGCCATGGGGATTGGCCTTATCATGCCAGTCTTGCCAACGTTATTACG TGAATTTATT

GCTTCGGAAGATATCGCTAACCACTTTGGCGTATTGCTTGCACTTTATGCGTTAATG CAGGTTATCT

TTGCTCCTTGGCTTGGAAAAATGTCTGACCGATTTGGTCGGCGCCCAGTGCTGTTGT TGTCATTAAT

AGGCGCATCGCTGGATTACTTATTGCTGGCTTTTTCAAGTGCGCTTTGGATGCTGTA TTTAGGCCGT

TTGCTTTCAGGGATCACAGGAGCTACTGGGGCTGTCGCGGCATCGGTCATTGCCGAT ACCACCTCA

GCTTCTCAACGCGTGAAGTGGTTCGGTTGGTTAGGGGCAAGTTTTGGGCTTGGTTTA ATAGCGGGG

CCTATTATTGGTGGTTTTGCAGGAGAGATTTCACCGCATAGTCCCTTTTTTATCGCT GCGTTGCTAA

ATATTGTCACTTTCCTTGTGGTTATGTTTTGGTTCCGTGAAACCAAAAATACACGTG ATAATACAGA

T ACCG A AGT AGGGGTTGAG ACGC A ATCG A ATTCGGT AT AC ATC ACTTT ATTT A A A ACG ATGCCC AT

TTTGTTGATTATTTATTTTTCAGCGCAATTGATAGGCCAAATTCCCGCAACGGTGTG GGTGCTATTT

ACCGAAAATCGTTTTGGATGGAATAGCATGATGGTTGGCTTTTCATTAGCGGGTCTT GGTCTTTTAC

ACTCAGTATTCCAAGCCTTTGTGGCAGGAAGAATAGCCACTAAATGGGGCGAAAAAA CGGCAGTA

CTGCTCGGATTTATTGCAGATAGTAGTGCATTTGCCTTTTTAGCGTTTATATCTGAA GGTTGGTTAG

TTTTCCCTGTTTTAATTTTATTGGCTGGTGGTGGGATCGCTTTACCTGCATTACAGG GAGTGATGTC

TATCCAAACAAAGAGTCATCAGCAAGGTGCTTTACAGGGATTATTGGTGAGCCTTAC CAATGCAAC

CGGTGTTATTGGCCCATTACTGTTTGCTGTTATTTATAATCATTCACTACCAATTTG GGATGGCTGG

ATTTGGATTATTGGTTTAGCGTTTTACTGTATTATTATCCTGCTATCGATGACCTTC ATGTTAACCCC

TCAAGCTCAGGGGAGTAAACAGGAGACAAGTGCTTAGTGATCCAATTCTTGAAG

* C1A (SEQ ID NO: 82)

CATCATCAATAATATACCTTATTTTGGATTGAAGCCAATATGATAATGAGGGGGTGGAGT TTGTGA

CGTGGCGCGGGGCGTGGGAACGGGGCGGGTGACGTAGTAGTGTGGCGGAAGTGTGAT GTTGCAAG

TGTGGCGGAACACATGTAAGCGACGGATGTGGCAAAAGTGACGTTTTTGGTGTGCGC CGGTGTAC

ACAGGAAGTGACAATTTTCGCGCGGTTTTAGGCGGATGTTGTAGTAAATTTGGGCGT AACCGAGTA

AGATTTGGCCATTTTCGCGGGAAAACTGAATAAGAGGAAGTGAAATCTGAATAATTT TGTGTTACT

CATAGCGCGTAATATTTGTCTAGGGCCGCGGGGACTTTGACCGTTTACGTGGAGACT CGCCCAGGT

_{GTTTTTCTCAGGTGTTTTCCGCGTTCCGGGTCAAAGTTGGCGTTTTATTATTATA GTCAGTCGAAGC}

TTGGATCCGGTACCTCTAGAATTCTCGAGCGGCCGCTAGCGACATCGGATCTCCCGA TCCCCTATG

GTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGTATCTGCTCCC TGCTTGTGTG

TTGGAGGTCGCTGAGTAGTGCGCGAGCAAAATTTAAGCTACAACAAGGCAAGGCTTG ACCGACAA

TTGCATGAAGAATCTGCTTAGGGTTAGGCGTTTTGCGCTGCTTCGCGATGTACGGGC CAGATATAC

GCGTTG AC ATTG ATT ATTG ACT AGTT ATT AAT AGT A ATC A ATT ACGGGGTC ATT AGTTC AT AGCCC

ATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCC CAACGACCC

CCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTT CCATTGACG

TCAATGGGTGGACTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCA TATGCCAAG

TACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTA CATGACCTT

ATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGT GATGCGGTTT

TGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTC CACCCCATT

GACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGT AACAACTCC

GCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGA GCTCTCTG

GCT A ACT AG AG A ACCC ACTGCTT ACTGGCTT ATCGA A ATG AG ACCC A AGCTGGCT AGTT A AGCT AT

CAACAAGTTTGTACAAAAAAGCAGGCTTTAAAGGAACCAATTCAGTCGACTGGATCC GGTACCAC

CATGTTCCTGAACTGCTGCCCAGGTTGCTGTATGGAGCCTGAATTCACCATGGTGAG CAAGGGCGA

GGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGG CCACAAGT

TCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGT TCATCTGC

ACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTGGGGC GTGCAGTGC

TTCGCCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCC GAAGGCTAC GTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGGTG AAGTT

CGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAAC

ATCCTGGGGCACAAGCTGGAGTACAACGCCATCAGCGACAACGTCTATATCACCGCC GACAAGCA

GAAGAACGGCATCAAGGCCAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGT GCAGCTCG

CCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACA ACCACTAC

CTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTC CTGCTGGA

GTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAGGTCGACTA TCCGTACGA

CGT ACC AG ACT ACGC AT A ACCGCGGCCGC ACTCG AG AT ATCT AG ACCC AGCTTTCTTGT AC A A AGT

GGTTGATCTAGAGGGCCCGCGGTTCGAAGGTAAGCCTATCCCTAACCCTCTCCTCGG TCTCGATTC

TACGCGTACCGGTTAGTAATGAGTTTAAACGGGGGAGGCTAACTGAAACACGGAAGG AGACAATA

CCGGAAGGAACCCGCGCTATGACGGCAATAAAAAGACAGAATAAAACGCACGGGTGT TGGGTCG

TTTGTTCATAAACGCGGGGTTCGGTCCCAGGGCTGGCACTCTGTCGATACCCCACCG AGACCCCAT

TGGGGCCAATACGCCCGCGTTTCTTCCTTTTCCCCACCCCACCCCCCAAGTTCGGGT GAAGGCCCA

GGGCTCGCAGCCAACGTCGGGGCGGCAGGCCCTGCCATAGCAGATCCGATTCGACAG ATCACTGA

AATGTGTGGGCGTGGCTTAAGGGTGGGAAAGAATATATAAGGTGGGGGTCTTATGTA GTTTTGTAT

CTGTTTTGCAGCAGCCGCCGCCGCCATGAGCACCAACTCGTTTGATGGAAGCATTGT GAGCTCATA

TTTGACAACGCGCATGCCCCCATGGGCCGGGGTGCGTCAGAATGTGATGGGCTCCAG CATTGATG

GTCGCCCCGTCCTGCCCGCAAACTCTACTACCTTGACCTACGAGACCGTGTCTGGAA CGCCGTTGG

AGACTGCAGCCTCCGCCGCCGCTTCAGCCGCTGCAGCCACCGCCCGCGGGATTGTGA CTGACTTTG

CTTTCCTGAGCCCGCTTGCAAGCAGTGCAGCTTCCCGTTCATCCGCCCGCGATGACA AGTTGACGG

CTCTTTTGGCACAATTGGATTCTTTGACCCGGGAACTTAATGTCGTTTCTCAGCAGC TGTTGGATCT

GCGCCAGCAGGTTTCTGCCCTGAAGGCTTCCTCCCCTCCCAATGCGGTTTAAAACAT AAATAAAAA

ACCAGACTCTGTTTGGATTTGGATCAAGCAAGTGTCTTGCTGTCTTTATTTAGGGGT TTTGCGCGCG

CGGTAGGCCCGGGACCAGCGGTCTCGGTCGTTGAGGGTCCTGTGTATTTTTTCCAGG ACGTGGTAA

AGGTGACTCTGGATGTTCAGATACATGGGCATAAGCCCGTCTCTGGGGTGGAGGTAG CACCACTG

CAGAGCTTCATGCTGCGGGGTGGTGTTGTAGATGATCCAGTCGTAGCAGGAGCGCTG GGCGTGGT

GCCTAAAAATGTCTTTCAGTAGCAAGCTGATTGCCAGGGGCAGGCCCTTGGTGTAAG TGTTTACAA

AGCGGTTAAGCTGGGATGGGTGCATACGTGGGGATATGAGATGCATCTTGGACTGTA TTTTTAGGT

TGGCTATGTTCCCAGCCATATCCCTCCGGGGATTCATGTTGTGCAGAACCACCAGCA CAGTGTATC

CGGTGCACTTGGGAAATTTGTCATGTAGCTTAGAAGGAAATGCGTGGAAGAACTTGG AGACGCCC

TTGTGACCTCCAAGATTTTCCATGCATTCGTCCATAATGATGGCAATGGGCCCACGG GCGGCGGCC

TGGGCGAAGATATTTCTGGGATCACTAACGTCATAGTTGTGTTCCAGGATGAGATCG TCATAGGCC

_{ATTTTTACAAAGCGCGGGCGGAGGGTGCCAGACTGCGGTATAATGGTTCCATCCG GCCCAGGGGC}

GTAGTTACCCTCACAGATTTGCATTTCCCACGCTTTGAGTTCAGATGGGGGGATCAT GTCTACCTGC

GGGGCGATGAAGAAAACGGTTTCCGGGGTAGGGGAGATCAGCTGGGAAGAAAGCAGG TTCCTGA

GCAGCTGCGACTTACCGCAGCCGGTGGGCCCGTAAATCACACCTATTACCGGCTGCA ACTGGTAGT

TAAGAGAGCTGCAGCTGCCGTCATCCCTGAGCAGGGGGGCCACTTCGTTAAGCATGT CCCTGACTC

GCATGTTTTCCCTGACCAAATCCGCCAGAAGGCGCTCGCCGCCCAGCGATAGCAGTT CTTGCAAGG

AAGCAAAGTTTTTCAACGGTTTGAGACCGTCCGCCGTAGGCATGCTTTTGAGCGTTT GACCAAGCA

GTTCCAGGCGGTCCCACAGCTCGGTCACCTGCTCTACGGCATCTCGATCCAGCATAT CTCCTCGTTT

CGCGGGTTGGGGCGGCTTTCGCTGTACGGCAGTAGTCGGTGCTCGTCCAGACGGGCC AGGGTCAT

GTCTTTCCACGGGCGCAGGGTCCTCGTCAGCGTAGTCTGGGTCACGGTGAAGGGGTG CGCTCCGGG

CTGCGCGCTGGCCAGGGTGCGCTTGAGGCTGGTCCTGCTGGTGCTGAAGCGCTGCCG GTCTTCGCC

CTGCGCGTCGGCCAGGTAGCATTTGACCATGGTGTCATAGTCCAGCCCCTCCGCGGC GTGGCCCTT

GGCGCGCAGCTTGCCCTTGGAGGAGGCGCCGCACGAGGGGCAGTGCAGACTTTTGAG GGCGTAGA

GCTTGGGCGCGAGAAATACCGATTCCGGGGAGTAGGCATCCGCGCCGCAGGCCCCGC AGACGGTC

TCGCATTCCACGAGCCAGGTGAGCTCTGGCCGTTCGGGGTCAAAAACCAGGTTTCCC CCATGCTTT

TTGATGCGTTTCTTACCTCTGGTTTCCATGAGCCGGTGTCCACGCTCGGTGACGAAA AGGCTGTCC

GTGTCCCCGTATACAGACTTGAGAGGCCTGTCCTCGAGCGGTGTTCCGCGGTCCTCC TCGTATAGA

AACTCGGACCACTCTGAGACAAAGGCTCGCGTCCAGGCCAGCACGAAGGAGGCTAAG TGGGAGG

GGTAGCGGTCGTTGTCCACTAGGGGGTCCACTCGCTCCAGGGTGTGAAGACACATGT CGCCCTCTT

CGGCATCAAGGAAGGTGATTGGTTTGTAGGTGTAGGCCACGTGACCGGGTGTTCCTG AAGGGGGG

CTATAAAAGGGGGTGGGGGCGCGTTCGTCCTCACTCTCTTCCGCATCGCTGTCTGCG AGGGCCAGC

TGTTGGGGTGAGTACTCCCTCTGAAAAGCGGGCATGACTTCTGCGCTAAGATTGTCA GTTTCCAAA

AACGAGGAGGATTTGATATTCACCTGGCCCGCGGTGATGCCTTTGAGGGTGGCCGCA TCCATCTGG

TCAGAAAAGACAATCTTTTTGTTGTCAAGCTTGGTGGCAAACGACCCGTAGAGGGCG TTGGACAG

CAACTTGGCGATGGAGCGCAGGGTTTGGTTTTTGTCGCGATCGGCGCGCTCCTTGGC CGCGATGTT

TAGCTGCACGTATTCGCGCGCAACGCACCGCCATTCGGGAAAGACGGTGGTGCGCTC GTCGGGCA

CCAGGTGCACGCGCCAACCGCGGTTGTGCAGGGTGACAAGGTCAACGCTGGTGGCTA CCTCTCCG CGTAGGCGCTCGTTGGTCCAGCAGAGGCGGCCGCCCTTGCGCGAGCAGAATGGCGGTAGG GGGTC

TAGCTGCGTCTCGTCCGGGGGGTCTGCGTCCACGGTAAAGACCCCGGGCAGCAGGCG CGCGTCGA

AGTAGTCTATCTTGCATCCTTGCAAGTCTAGCGCCTGCTGCCATGCGCGGGCGGCAA GCGCGCGCT

CGTATGGGTTGAGTGGGGGACCCCATGGCATGGGGTGGGTGAGCGCGGAGGCGTACA TGCCGCAA

ATGTCGTAAACGTAGAGGGGCTCTCTGAGTATTCCAAGATATGTAGGGTAGCATCTT CCACCGCGG

ATGCTGGCGCGCACGTAATCGTATAGTTCGTGCGAGGGAGCGAGGAGGTCGGGACCG AGGTTGCT

ACGGGCGGGCTGCTCTGCTCGGAAGACTATCTGCCTGAAGATGGCATGTGAGTTGGA TGATATGGT

TGGACGCTGGAAGACGTTGAAGCTGGCGTCTGTGAGACCTACCGCGTCACGCACGAA GGAGGCGT

AGGAGTCGCGCAGCTTGTTGACCAGCTCGGCGGTGACCTGCACGTCTAGGGCGCAGT AGTCCAGG

GTTTCCTTGATGATGTCATACTTATCCTGTCCCTTTTTTTTCCACAGCTCGCGGTTG AGGACAAACT

CTTCGCGGTCTTTCCAGTACTCTTGGATCGGAAACCCGTCGGCCTCCGAACGGTAAG AGCCTAGCA

TGTAGAACTGGTTGACGGCCTGGTAGGCGCAGCATCCCTTTTCTACGGGTAGCGCGT ATGCCTGCG

CGGCCTTCCGGAGCGAGGTGTGGGTGAGCGCAAAGGTGTCCCTGACCATGACCAGCA TGAAGGGC

ACGAGCTGCTTCCCAAAGGCCCCCATCCAAGTATAGGTCTCTACATCGTAGGTGACA AAGAGACG

CTCGGTGCGAGGATGCGAGCCGATCGGGAAGAACTGGATCTCCCGCCACCAATTGGA GGAGTGGC

TATTGATGTGGTGAAAGTAGAAGTCCCTGCGACGGGCCGAACACTCGTGCTGGCTTT TGTAAAAAC

GTGCGCAGTACTGGCAGCGGTGCACGGGCTGTACATCCTGCACGAGGTTGACCTGAC GACCGCGC

ACAAGGAAGCAGAGTGGGAATTTGAGCCCCTCGCCTGGCGGGTTTGGCTGGTGGTCT TCTACTTCG

GCTGCTTGTCCTTGACCGTCTGGCTGCTCGAGGGGAGTTACGGTGGATCGGACCACC ACGCCGCGC

GAGCCCAAAGTCCAGATGTCCGCGCGCGGCGGTCGGAGCTTGATGACAACATCGCGC AGATGGGA

GCTGTCCATGGTCTGGAGCTCCCGCGGCGTCAGGTCAGGCGGGAGCTCCTGCAGGTT TACCTCGCA

TAGACGGGTCAGGGCGCGGGCTAGATCCAGGTGATACCTAATTTCCAGGGGCTGGTT GGTGGCGG

CGTCGATGGCTTGCAAGAGGCCGCATCCCCGCGGCGCGACTACGGTACCGCGCGGCG GGCGGTGG

GCCGCGGGGGTGTCCTTGGATGATGCATCTAAAAGCGGTGACGCGGGCGAGCCCCCG GAGGTAGG

GGGGGCTCCGGACCCGCCGGGAGAGGGGGCAGGGGCACGTCGGCGCCGCGCGCGGGC AGGAGCT

GGTGCTGCGCGCGTAGGTTGCTGGCGAACGCGACGACGCGGCGGTTGATCTCCTGAA TCTGGCGC

CTCTGCGTGAAGACGACGGGCCCGGTGAGCTTGAACCTGAAAGAGAGTTCGACAGAA TCAATTTC

GGTGTCGTTGACGGCGGCCTGGCGCAAAATCTCCTGCACGTCTCCTGAGTTGTCTTG ATAGGCGAT

CTCGGCCATGAACTGCTCGATCTCTTCCTCCTGGAGATCTCCGCGTCCGGCTCGCTC CACGGTGGC

GGCGAGGTCGTTGGAAATGCGGGCCATGAGCTGCGAGAAGGCGTTGAGGCCTCCCTC GTTCCAGA

CGCGGCTGTAGACCACGCCCCCTTCGGCATCGCGGGCGCGCATGACCACCTGCGCGA GATTGAGC

TCCACGTGCCGGGCGAAGACGGCGTAGTTTCGCAGGCGCTGAAAGAGGTAGTTGAGG GTGGTGGC

GGTGTGTTCTGCCACGAAGAAGTACATAACCCAGCGTCGCAACGTGGATTCGTTGAT ATCCCCCAA

GGCCTCAAGGCGCTCCATGGCCTCGTAGAAGTCCACGGCGAAGTTGAAAAACTGGGA GTTGCGCG

CCGACACGGTTAACTCCTCCTCCAGAAGACGGATGAGCTCGGCGACAGTGTCGCGCA CCTCGCGCT

CAAAGGCTACAGGGGCCTCTTCTTCTTCTTCAATCTCCTCTTCCATAAGGGCCTCCC CTTCTTCTTCT

TCTGGCGGCGGTGGGGGAGGGGGGACACGGCGGCGACGACGGCGCACCGGGAGGCGG TCGACAA

AGCGCTCGATCATCTCCCCGCGGCGACGGCGCATGGTCTCGGTGACGGCGCGGCCGT TCTCGCGGG

GGCGCAGTTGGAAGACGCCGCCCGTCATGTCCCGGTTATGGGTTGGCGGGGGGCTGC CATGCGGC

AGGGATACGGCGCTAACGATGCATCTCAACAATTGTTGTGTAGGTACTCCGCCGCCG AGGGACCT

GAGCGAGTCCGCATCGACCGGATCGGAAAACCTCTCGAGAAAGGCGTCTAACCAGTC ACAGTCGC

AAGGTAGGCTGAGCACCGTGGCGGGCGGCAGCGGGCGGCGGTCGGGGTTGTTTCTGG CGGAGGTG

CTGCTGATGATGTAATTAAAGTAGGCGGTCTTGAGACGGCGGATGGTCGACAGAAGC ACCATGTC

CTTGGGTCCGGCCTGCTGAATGCGCAGGCGGTCGGCCATGCCCCAGGCTTCGTTTTG ACATCGGCG

CAGGTCTTTGTAGTAGTCTTGCATGAGCCTTTCTACCGGCACTTCTTCTTCTCCTTC CTCTTGTCCTG

CATCTCTTGCATCTATCGCTGCGGCGGCGGCGGAGTTTGGCCGTAGGTGGCGCCCTC TTCCTCCCAT

GCGTGTGACCCCGAAGCCCCTCATCGGCTGAAGCAGGGCTAGGTCGGCGACAACGCG CTCGGCTA

ATATGGCCTGCTGCACCTGCGTGAGGGTAGACTGGAAGTCATCCATGTCCACAAAGC GGTGGTAT

GCGCCCGTGTTGATGGTGTAAGTGCAGTTGGCCATAACGGACCAGTTAACGGTCTGG TGACCCGGC

TGCGAGAGCTCGGTGTACCTGAGACGCGAGTAAGCCCTCGAGTCAAATACGTAGTCG TTGCAAGT

CCGCACCAGGTACTGGTATCCCACCAAAAAGTGCGGCGGCGGCTGGCGGTAGAGGGG CCAGCGTA

GGGTGGCCGGGGCTCCGGGGGCGAGATCTTCCAACATAAGGCGATGATATCCGTAGA TGTACCTG

GACATCCAGGTGATGCCGGCGGCGGTGGTGGAGGCGCGCGGAAAGTCGCGGACGCGG TTCCAGAT

GTTGCGCAGCGGCAAAAAGTGCTCCATGGTCGGGACGCTCTGGCCGGTCAGGCGCGC GCAATCGT

TGACGCTCTAGACCGTGCAAAAGGAGAGCCTGTAAGCGGGCACTCTTCCGTGGTCTG GTGGATAA

ATTCGCAAGGGTATCATGGCGGACGACCGGGGTTCGAGCCCCGTATCCGGCCGTCCG CCGTGATCC

ATGCGGTTACCGCCCGCGTGTCGAACCCAGGTGTGCGACGTCAGACAACGGGGGAGT GCTCCTTTT

GGCTTCCTTCCAGGCGCGGCGGCTGCTGCGCTAGCTTTTTTGGCCACTGGCCGCGCG CAGCGTAAG

CGGTTAGGCTGGAAAGCGAAAGCATTAAGTGGCTCGCTCCCTGTAGCCGGAGGGTTA TTTTCCAAG GGTTGAGTCGCGGGACCCCCGGTTCGAGTCTCGGACCGGCCGGACTGCGGCGAACGGGGG TTTGC

CTCCCCGTCATGCAAGACCCCGCTTGCAAATTCCTCCGGAAACAGGGACGAGCCCCT TTTTTGCTT

TTCCCAGATGCATCCGGTGCTGCGGCAGATGCGCCCCCCTCCTCAGCAGCGGCAAGA GCAAGAGC

AGCGGCAGACATGCAGGGCACCCTCCCCTCCTCCTACCGCGTCAGGAGGGGCGACAT CCGCGGTT

GACGCGGCAGCAGATGGTGATTACGAACCCCCGCGGCGCCGGGCCCGGCACTACCTG GACTTGGA

GGAGGGCGAGGGCCTGGCGCGGCTAGGAGCGCCCTCTCCTGAGCGGCACCCAAGGGT GCAGCTGA

AGCGTGATACGCGTGAGGCGTACGTGCCGCGGCAGAACCTGTTTCGCGACCGCGAGG GAGAGGAG

CCCGAGGAGATGCGGGATCGAAAGTTCCACGCAGGGCGCGAGCTGCGGCATGGCCTG AATCGCGA

GCGGTTGCTGCGCGAGGAGGACTTTGAGCCCGACGCGCGAACCGGGATTAGTCCCGC GCGCGCAC

ACGTGGCGGCCGCCGACCTGGTAACCGCATACGAGCAGACGGTGAACCAGGAGATTA ACTTTCAA

AAAAGCTTTAACAACCACGTGCGTACGCTTGTGGCGCGCGAGGAGGTGGCTATAGGA CTGATGCA

TCTGTGGGACTTTGTAAGCGCGCTGGAGCAAAACCCAAATAGCAAGCCGCTCATGGC GCAGCTGT

TCCTTATAGTGCAGCACAGCAGGGACAACGAGGCATTCAGGGATGCGCTGCTAAACA TAGTAGAG

CCCGAGGGCCGCTGGCTGCTCGATTTGATAAACATCCTGCAGAGCATAGTGGTGCAG GAGCGCAG

CTTGAGCCTGGCTGACAAGGTGGCCGCCATCAACTATTCCATGCTTAGCCTGGGCAA GTTTTACGC

CCGCAAGATATACCATACCCCTTACGTTCCCATAGACAAGGAGGTAAAGATCGAGGG GTTCTACA

TGCGCATGGCGCTGAAGGTGCTTACCTTGAGCGACGACCTGGGCGTTTATCGCAACG AGCGCATCC

ACAAGGCCGTGAGCGTGAGCCGGCGGCGCGAGCTCAGCGACCGCGAGCTGATGCACA GCCTGCAA

AGGGCCCTGGCTGGCACGGGCAGCGGCGATAGAGAGGCCGAGTCCTACTTTGACGCG GGCGCTGA

CCTGCGCTGGGCCCCAAGCCGACGCGCCCTGGAGGCAGCTGGGGCCGGACCTGGGCT GGCGGTGG

CACCCGCGCGCGCTGGCAACGTCGGCGGCGTGGAGGAATATGACGAGGACGATGAGT ACGAGCC

AGAGGACGGCGAGTACTAAGCGGTGATGTTTCTGATCAGATGATGCAAGACGCAACG GACCCGGC

GGTGCGGGCGGCGCTGCAGAGCCAGCCGTCCGGCCTTAACTCCACGGACGACTGGCG CCAGGTCA

TGGACCGCATCATGTCGCTGACTGCGCGCAATCCTGACGCGTTCCGGCAGCAGCCGC AGGCCAAC

CGGCTCTCCGCAATTCTGGAAGCGGTGGTCCCGGCGCGCGCAAACCCCACGCACGAG AAGGTGCT

GGCGATCGTAAACGCGCTGGCCGAAAACAGGGCCATCCGGCCCGACGAGGCCGGCCT GGTCTACG

ACGCGCTGCTTCAGCGCGTGGCTCGTTACAACAGCGGCAACGTGCAGACCAACCTGG ACCGGCTG

GTGGGGGATGTGCGCGAGGCCGTGGCGCAGCGTGAGCGCGCGCAGCAGCAGGGCAAC CTGGGCT

CCATGGTTGCACTAAACGCCTTCCTGAGTACACAGCCCGCCAACGTGCCGCGGGGAC AGGAGGAC

TACACCAACTTTGTGAGCGCACTGCGGCTAATGGTGACTGAGACACCGCAAAGTGAG GTGTACCA

GTCTGGGCCAGACTATTTTTTCCAGACCAGTAGACAAGGCCTGCAGACCGTAAACCT GAGCCAGG

CTTTCAAAAACTTGCAGGGGCTGTGGGGGGTGCGGGCTCCCACAGGCGACCGCGCGA CCGTGTCT

AGCTTGCTGACGCCCAACTCGCGCCTGTTGCTGCTGCTAATAGCGCCCTTCACGGAC AGTGGCAGC

GTGTCCCGGGACACATACCTAGGTCACTTGCTGACACTGTACCGCGAGGCCATAGGT CAGGCGCAT

GTGGACGAGCATACTTTCCAGGAGATTACAAGTGTCAGCCGCGCGCTGGGGCAGGAG GACACGGG

CAGCCTGGAGGCAACCCTAAACTACCTGCTGACCAACCGGCGGCAGAAGATCCCCTC GTTGCACA

GTTTAAACAGCGAGGAGGAGCGCATTTTGCGCTACGTGCAGCAGAGCGTGAGCCTTA ACCTGATG

CGCGACGGGGTAACGCCCAGCGTGGCGCTGGACATGACCGCGCGCAACATGGAACCG GGCATGTA

TGCCTCAAACCGGCCGTTTATCAACCGCCTAATGGACTACTTGCATCGCGCGGCCGC CGTGAACCC

CGAGTATTTCACCAATGCCATCTTGAACCCGCACTGGCTACCGCCCCCTGGTTTCTA CACCGGGGG

ATTCGAGGTGCCCGAGGGTAACGATGGATTCCTCTGGGACGACATAGACGACAGCGT GTTTTCCCC

GCAACCGCAGACCCTGCTAGAGTTGCAACAGCGCGAGCAGGCAGAGGCGGCGCTGCG AAAGGAA

AGCTTCCGCAGGCCAAGCAGCTTGTCCGATCTAGGCGCTGCGGCCCCGCGGTCAGAT GCTAGTAGC

CCATTTCCAAGCTTGATAGGGTCTCTTACCAGCACTCGCACCACCCGCCCGCGCCTG CTGGGCGAG

GAGGAGTACCTAAACAACTCGCTGCTGCAGCCGCAGCGCGAAAAAAACCTGCCTCCG GCATTTCC

CAACAACGGGATAGAGAGCCTAGTGGACAAGATGAGTAGATGGAAGACGTACGCGCA GGAGCAC

AGGGACGTGCCAGGCCCGCGCCCGCCCACCCGTCGTCAAAGGCACGACCGTCAGCGG GGTCTGGT

GTGGGAGGACGATGACTCGGCAGACGACAGCAGCGTCCTGGATTTGGGAGGGAGTGG CAACCCGT

TTGCGCACCTTCGCCCCAGGCTGGGGAGAATGTTTTAAAAAAAAAAAAAGCATGATG CAAAATAA

AAAACTCACCAAGGCCATGGCACCGAGCGTTGGTTTTCTTGTATTCCCCTTAGTATG CGGCGCGCG

GCGATGTATGAGGAAGGTCCTCCTCCCTCCTACGAGAGTGTGGTGAGCGCGGCGCCA GTGGCGGC

GGCGCTGGGTTCTCCCTTCGATGCTCCCCTGGACCCGCCGTTTGTGCCTCCGCGGTA CCTGCGGCCT

ACCGGGGGGAGAAACAGCATCCGTTACTCTGAGTTGGCACCCCTATTCGACACCACC CGTGTGTAC

CTGGTGGACAACAAGTCAACGGATGTGGCATCCCTGAACTACCAGAACGACCACAGC AACTTTCT

GACCACGGTCATTCAAAACAATGACTACAGCCCGGGGGAGGCAAGCACACAGACCAT CAATCTTG

ACGACCGGTCGCACTGGGGCGGCGACCTGAAAACCATCCTGCATACCAACATGCCAA ATGTGAAC

GAGTTCATGTTTACCAATAAGTTTAAGGCGCGGGTGATGGTGTCGCGCTTGCCTACT AAGGACAAT

CAGGTGGAGCTGAAATACGAGTGGGTGGAGTTCACGCTGCCCGAGGGCAACTACTCC GAGACCAT

GACCATAGACCTTATGAACAACGCGATCGTGGAGCACTACTTGAAAGTGGGCAGACA GAACGGGG TTCTGGAAAGCGACATCGGGGTAAAGTTTGACACCCGCAACTTCAGACTGGGGTTTGACC CCGTCA

CTGGTCTTGTCATGCCTGGGGTATATACAAACGAAGCCTTCCATCCAGACATCATTT TGCTGCCAG

GATGCGGGGTGGACTTCACCCACAGCCGCCTGAGCAACTTGTTGGGCATCCGCAAGC GGCAACCC

TTCCAGGAGGGCTTTAGGATCACCTACGATGATCTGGAGGGTGGTAACATTCCCGCA CTGTTGGAT

GTGGACGCCTACCAGGCGAGCTTGAAAGATGACACCGAACAGGGCGGGGGTGGCGCA GGCGGCA

GCAACAGCAGTGGCAGCGGCGCGGAAGAGAACTCCAACGCGGCAGCCGCGGCAATGC AGCCGGT

GGAGGACATGAACGATCATGCCATTCGCGGCGACACCTTTGCCACACGGGCTGAGGA GAAGCGCG

CTGAGGCCGAAGCAGCGGCCGAAGCTGCCGCCCCCGCTGCGCAACCCGAGGTCGAGA AGCCTCAG

AAGAAACCGGTGATCAAACCCCTGACAGAGGACAGCAAGAAACGCAGTTACAACCTA ATAAGCA

ATGACAGCACCTTCACCCAGTACCGCAGCTGGTACCTTGCATACAACTACGGCGACC CTCAGACCG

GAATCCGCTCATGGACCCTGCTTTGCACTCCTGACGTAACCTGCGGCTCGGAGCAGG TCTACTGGT

CGTTGCCAGACATGATGCAAGACCCCGTGACCTTCCGCTCCACGCGCCAGATCAGCA ACTTTCCGG

TGGTGGGCGCCGAGCTGTTGCCCGTGCACTCCAAGAGCTTCTACAACGACCAGGCCG TCTACTCCC

AACTCATCCGCCAGTTTACCTCTCTGACCCACGTGTTCAATCGCTTTCCCGAGAACC AGATTTTGGC

GCGCCCGCCAGCCCCCACCATCACCACCGTCAGTGAAAACGTTCCTGCTCTCACAGA TCACGGGAC

GCTACCGCTGCGCAACAGCATCGGAGGAGTCCAGCGAGTGACCATTACTGACGCCAG ACGCCGCA

CCTGCCCCTACGTTTACAAGGCCCTGGGCATAGTCTCGCCGCGCGTCCTATCGAGCC GCACTTTTTG

AGCAAGCATGTCCATCCTTATATCGCCCAGCAATAACACAGGCTGGGGCCTGCGCTT CCCAAGCAA

GATGTTTGGCGGGGCCAAGAAGCGCTCCGACCAACACCCAGTGCGCGTGCGCGGGCA CTACCGCG

CGCCCTGGGGCGCGCACAAACGCGGCCGCACTGGGCGCACCACCGTCGATGACGCCA TCGACGCG

GTGGTGGAGGAGGCGCGCAACTACACGCCCACGCCGCCACCAGTGTCCACAGTGGAC GCGGCCAT

TCAGACCGTGGTGCGCGGAGCCCGGCGCTATGCTAAAATGAAGAGACGGCGGAGGCG CGTAGCAC

GTCGCCACCGCCGCCGACCCGGCACTGCCGCCCAACGCGCGGCGGCGGCCCTGCTTA ACCGCGCA

CGTCGCACCGGCCGACGGGCGGCCATGCGGGCCGCTCGAAGGCTGGCCGCGGGTATT GTCACTGT

GCCCCCCAGGTCCAGGCGACGAGCGGCCGCCGCAGCAGCCGCGGCCATTAGTGCTAT GACTCAGG

GTCGCAGGGGCAACGTGTATTGGGTGCGCGACTCGGTTAGCGGCCTGCGCGTGCCCG TGCGCACC

CGCCCCCCGCGC A ACT AG ATTGC A AG A A A A A ACT ACTT AG ACTCGT ACTGTTGT ATGT ATCC AGCG

GCGGCGGCGCGCAACGAAGCTATGTCCAAGCGCAAAATCAAAGAAGAGATGCTCCAG GTCATCGC

GCCGGAGATCTATGGCCCCCCGAAGAAGGAAGAGCAGGATTACAAGCCCCGAAAGCT AAAGCGG

GTCAAAAAGAAAAAGAAAGATGATGATGATGAACTTGACGACGAGGTGGAACTGCTG CACGCTA

CCGCGCCCAGGCGACGGGTACAGTGGAAAGGTCGACGCGTAAAACGTGTTTTGCGAC CCGGCACC

ACCGTAGTCTTTACGCCCGGTGAGCGCTCCACCCGCACCTACAAGCGCGTGTATGAT GAGGTGTAC

GGCGACGAGGACCTGCTTGAGCAGGCCAACGAGCGCCTCGGGGAGTTTGCCTACGGA AAGCGGCA

TAAGGACATGCTGGCGTTGCCGCTGGACGAGGGCAACCCAACACCTAGCCTAAAGCC CGTAACAC

TGCAGCAGGTGCTGCCCGCGCTTGCACCGTCCGAAGAAAAGCGCGGCCTAAAGCGCG AGTCTGGT

GACTTGGCACCCACCGTGCAGCTGATGGTACCCAAGCGCCAGCGACTGGAAGATGTC TTGGAAAA

AATGACCGTGGAACCTGGGCTGGAGCCCGAGGTCCGCGTGCGGCCAATCAAGCAGGT GGCGCCGG

GACTGGGCGTGCAGACCGTGGACGTTCAGATACCCACTACCAGTAGCACCAGTATTG CCACCGCC

ACAGAGGGCATGGAGACACAAACGTCCCCGGTTGCCTCAGCGGTGGCGGATGCCGCG GTGCAGGC

GGTCGCTGCGGCCGCGTCCAAGACCTCTACGGAGGTGCAAACGGACCCGTGGATGTT TCGCGTTTC

AGCCCCCCGGCGCCCGCGCCGTTCGAGGAAGTACGGCGCCGCCAGCGCGCTACTGCC CGAATATG

CCCTACATCCTTCCATTGCGCCTACCCCCGGCTATCGTGGCTACACCTACCGCCCCA GAAGACGAG

CAACTACCCGACGCCGAACCACCACTGGAACCCGCCGCCGCCGTCGCCGTCGCCAGC CCGTGCTG

GCCCCGATTTCCGTGCGCAGGGTGGCTCGCGAAGGAGGCAGGACCCTGGTGCTGCCA ACAGCGCG

CTACCACCCCAGCATCGTTTAAAAGCCGGTCTTTGTGGTTCTTGCAGATATGGCCCT CACCTGCCGC

CTCCGTTTCCCGGTGCCGGGATTCCGAGGAAGAATGCACCGTAGGAGGGGCATGGCC GGCCACGG

CCTGACGGGCGGCATGCGTCGTGCGCACCACCGGCGGCGGCGCGCGTCGCACCGTCG CATGCGCG

GCGGTATCCTGCCCCTCCTTATTCCACTGATCGCCGCGGCGATTGGCGCCGTGCCCG GAATTGCAT

CCGTGGCCTTGCAGGCGCAGAGACACTGATTAAAAACAAGTTGCATGTGGAAAAATC AAAATAAA

AAGTCTGGACTCTCACGCTCGCTTGGTCCTGTAACTATTTTGTAGAATGGAAGACAT CAACTTTGC

GTCTCTGGCCCCGCGACACGGCTCGCGCCCGTTCATGGGAAACTGGCAAGATATCGG CACCAGCA

ATATGAGCGGTGGCGCCTTCAGCTGGGGCTCGCTGTGGAGCGGCATTAAAAATTTCG GTTCCACCG

TTAAGAACTATGGCAGCAAGGCCTGGAACAGCAGCACAGGCCAGATGCTGAGGGATA AGTTGAA

AGAGCAAAATTTCCAACAAAAGGTGGTAGATGGCCTGGCCTCTGGCATTAGCGGGGT GGTGGACC

TGGCCAACCAGGCAGTGCAAAATAAGATTAACAGTAAGCTTGATCCCCGCCCTCCCG TAGAGGAG

CCTCCACCGGCCGTGGAGACAGTGTCTCCAGAGGGGCGTGGCGAAAAGCGTCCGCGC CCCGACAG

GGAAGAAACTCTGGTGACGCAAATAGACGAGCCTCCCTCGTACGAGGAGGCACTAAA GCAAGGCC

TGCCCACCACCCGTCCCATCGCGCCCATGGCTACCGGAGTGCTGGGCCAGCACACAC CCGTAACGC

TGGACCTGCCTCCCCCCGCCGACACCCAGCAGAAACCTGTGCTGCCAGGCCCGACCG CCGTTGTTG TAACCCGTCCTAGCCGCGCGTCCCTGCGCCGCGCCGCCAGCGGTCCGCGATCGTTGCGGC CCGTAG

CCAGTGGCAACTGGCAAAGCACACTGAACAGCATCGTGGGTCTGGGGGTGCAATCCC TGAAGCGC

CGACGATGCTTCTGATAGCTAACGTGTCGTATGTGTGTCATGTATGCGTCCATGTCG CCGCCAGAG

GAGCTGCTGAGCCGCCGCGCGCCCGCTTTCCAAGATGGCTACCCCTTCGATGATGCC GCAGTGGTC

TTACATGCACATCTCGGGCCAGGACGCCTCGGAGTACCTGAGCCCCGGGCTGGTGCA GTTTGCCCG

CGCCACCGAGACGTACTTCAGCCTGAATAACAAGTTTAGAAACCCCACGGTGGCGCC TACGCACG

ACGTGACCACAGACCGGTCCCAGCGTTTGACGCTGCGGTTCATCCCTGTGGACCGTG AGGATACTG

CGTACTCGTACAAGGCGCGGTTCACCCTAGCTGTGGGTGATAACCGTGTGCTGGACA TGGCTTCCA

CGTACTTTGACATCCGCGGCGTGCTGGACAGGGGCCCTACTTTTAAGCCCTACTCTG GCACTGCCT

ACAACGCCCTGGCTCCCAAGGGTGCCCCAAATCCTTGCGAATGGGATGAAGCTGCTA CTGCTCTTG

AAATAAACCTAGAAGAAGAGGACGATGACAACGAAGACGAAGTAGACGAGCAAGCTG AGCAGCA

A A A A ACTC ACGT ATTTGGGC AGGCGCCTT ATTCTGGT AT AA AT ATT AC A A AGG AGGGT ATTC A A AT

AGGTGTCGAAGGTCAAACACCTAAATATGCCGATAAAACATTTCAACCTGAACCTCA AATAGGAG

AATCTCAGTGGTACGAAACAGAAATTAATCATGCAGCTGGGAGAGTCCTAAAAAAGA CTACCCCA

ATGAAACCATGTTACGGTTCATATGCAAAACCCACAAATGAAAATGGAGGGCAAGGC ATTCTTGT

AAAGCAACAAAATGGAAAGCTAGAAAGTCAAGTGGAAATGCAATTTTTCTCAACTAC TGAGGCAG

CCGCAGGCAATGGTGATAACTTGACTCCTAAAGTGGTATTGTACAGTGAAGATGTAG ATATAGAA

ACCCCAGACACTCATATTTCTTACATGCCCACTATTAAGGAAGGTAACTCACGAGAA CTAATGGGC

C A AC A ATCT ATGCCC A AC AGGCCT A ATT AC ATTGCTTTT AGGG AC A ATTTT ATTGGTCT AATGT ATT

ACAACAGCACGGGTAATATGGGTGTTCTGGCGGGCCAAGCATCGCAGTTGAATGCTG TTGTAGATT

TGCAAGACAGAAACACAGAGCTTTCATACCAGCTTTTGCTTGATTCCATTGGTGATA GAACCAGGT

ACTTTTCTATGTGGAATCAGGCTGTTGACAGCTATGATCCAGATGTTAGAATTATTG AAAATCATG

GAACTGAAGATGAACTTCCAAATTACTGCTTTCCACTGGGAGGTGTGATTAATACAG AGACTCTTA

CCAAGGTAAAACCTAAAACAGGTCAGGAAAATGGATGGGAAAAAGATGCTACAGAAT TTTCAGAT

AAAAATGAAATAAGAGTTGGAAATAATTTTGCCATGGAAATCAATCTAAATGCCAAC CTGTGGAG

A A ATTTCCTGT ACTCC A AC AT AGCGCTGT ATTTGCCCG AC A AGCT A A AGT AC AGTCCTTCC A ACGT

AAAAATTTCTGATAACCCAAACACCTACGACTACATGAACAAGCGAGTGGTGGCTCC CGGGCTAG

TGGACTGCTACATTAACCTTGGAGCACGCTGGTCCCTTGACTATATGGACAACGTCA ACCCATTTA

ACCACCACCGCAATGCTGGCCTGCGCTACCGCTCAATGTTGCTGGGCAATGGTCGCT ATGTGCCCT

TCCACATCCAGGTGCCTCAGAAGTTCTTTGCCATTAAAAACCTCCTTCTCCTGCCGG GCTCATACAC

CTACGAGTGGAACTTCAGGAAGGATGTTAACATGGTTCTGCAGAGCTCCCTAGGAAA TGACCTAA

GGGTTGACGGAGCCAGCATTAAGTTTGATAGCATTTGCCTTTACGCCACCTTCTTCC CCATGGCCC

ACAACACCGCCTCCACGCTTGAGGCCATGCTTAGAAACGACACCAACGACCAGTCCT TTAACGACT

ATCTCTCCGCCGCC A AC ATGCTCT ACCCT AT ACCCGCC A ACGCT ACC A ACGTGCCC AT ATCC ATCC

CCTCCCGCAACTGGGCGGCTTTCCGCGGCTGGGCCTTCACGCGCCTTAAGACTAAGG AAACCCCAT

C ACTGGGCTCGGGCT ACG ACCCTT ATT AC ACCT ACTCTGGCTCT AT ACCCT ACCT AG ATGG A ACCTT

TTACCTCAACCACACCTTTAAGAAGGTGGCCATTACCTTTGACTCTTCTGTCAGCTG GCCTGGCAAT

GACCGCCTGCTTACCCCCAACGAGTTTGAAATTAAGCGCTCAGTTGACGGGGAGGGT TACAACGTT

GCCCAGTGTAACATGACCAAAGACTGGTTCCTGGTACAAATGCTAGCTAACTATAAC ATTGGCTAC

C AGGGCTTCT AT ATCCC AG AG AGCT AC A AGG ACCGC ATGT ACTCCTTCTTT AG A A ACTTCC AGCCC

ATGAGCCGTCAGGTGGTGGATGATACTAAATACAAGGACTACCAACAGGTGGGCATC CTACACCA

ACACAACAACTCTGGATTTGTTGGCTACCTTGCCCCCACCATGCGCGAAGGACAGGC CTACCCTGC

T AACTTCCCCT ATCCGCTT AT AGGC A AG ACCGC AGTTG AC AGC ATT ACCC AG A A A A AGTTTCTTTG

CGATCGCACCCTTTGGCGCATCCCATTCTCCAGTAACTTTATGTCCATGGGCGCACT CACAGACCT

GGGCCAAAACCTTCTCTACGCCAACTCCGCCCACGCGCTAGACATGACTTTTGAGGT GGATCCCAT

GGACGAGCCCACCCTTCTTTATGTTTTGTTTGAAGTCTTTGACGTGGTCCGTGTGCA CCAGCCGCAC

CGCGGCGTCATCGAAACCGTGTACCTGCGCACGCCCTTCTCGGCCGGCAACGCCACA ACATAAAG

AAGCAAGCAACATCAACAACAGCTGCCGCCATGGGCTCCAGTGAGCAGGAACTGAAA GCCATTGT

CAAAGATCTTGGTTGTGGGCCATATTTTTTGGGCACCTATGACAAGCGCTTTCCAGG CTTTGTTTCT

CCACACAAGCTCGCCTGCGCCATAGTCAATACGGCCGGTCGCGAGACTGGGGGCGTA CACTGGAT

GGCCTTTGCCTGGAACCCGCACTCAAAAACATGCTACCTCTTTGAGCCCTTTGGCTT TTCTGACCAG

CGACTCAAGCAGGTTTACCAGTTTGAGTACGAGTCACTCCTGCGCCGTAGCGCCATT GCTTCTTCC

CCCGACCGCTGTATAACGCTGGAAAAGTCCACCCAAAGCGTACAGGGGCCCAACTCG GCCGCCTG

TGGACTATTCTGCTGCATGTTTCTCCACGCCTTTGCCAACTGGCCCCAAACTCCCAT GGATCACAAC

CCCACCATGAACCTTATTACCGGGGTACCCAACTCCATGCTCAACAGTCCCCAGGTA CAGCCCACC

CTGCGTCGCAACCAGGAACAGCTCTACAGCTTCCTGGAGCGCCACTCGCCCTACTTC CGCAGCCAC

AGTGCGCAGATT AGG AGCGCCACTTCTTTTTGTCACTTGAAAAACATGT AAAAAT AATGT ACT AGA

GACACTTTCAATAAAGGCAAATGCTTTTATTTGTACACTCTCGGGTGATTATTTACC CCCACCCTTG

CCGTCTGCGCCGTTTAAAAATCAAAGGGGTTCTGCCGCGCATCGCTATGCGCCACTG GCAGGGACA CGTTGCGATACTGGTGTTTAGTGCTCCACTTAAACTCAGGCACAACCATCCGCGGCAGCT CGGTGA

AGTTTTCACTCCACAGGCTGCGCACCATCACCAACGCGTTTAGCAGGTCGGGCGCCG ATATCTTGA

AGTCGCAGTTGGGGCCTCCGCCCTGCGCGCGCGAGTTGCGATACACAGGGTTGCAGC ACTGGAAC

ACTATCAGCGCCGGGTGGTGCACGCTGGCCAGCACGCTCTTGTCGGAGATCAGATCC GCGTCCAG

GTCCTCCGCGTTGCTCAGGGCGAACGGAGTCAACTTTGGTAGCTGCCTTCCCAAAAA GGGCGCGTG

CCCAGGCTTTGAGTTGCACTCGCACCGTAGTGGCATCAAAAGGTGACCGTGCCCGGT CTGGGCGTT

AGGATACAGCGCCTGCATAAAAGCCTTGATCTGCTTAAAAGCCACCTGAGCCTTTGC GCCTTCAGA

GAAGAACATGCCGCAAGACTTGCCGGAAAACTGATTGGCCGGACAGGCCGCGTCGTG CACGCAGC

ACCTTGCGTCGGTGTTGGAGATCTGCACCACATTTCGGCCCCACCGGTTCTTCACGA TCTTGGCCTT

GCTAGACTGCTCCTTCAGCGCGCGCTGCCCGTTTTCGCTCGTCACATCCATTTCAAT CACGTGCTCC

TTATTTATCATAATGCTTCCGTGTAGACACTTAAGCTCGCCTTCGATCTCAGCGCAG CGGTGCAGCC

ACAACGCGCAGCCCGTGGGCTCGTGATGCTTGTAGGTCACCTCTGCAAACGACTGCA GGTACGCCT

GCAGGAATCGCCCCATCATCGTCACAAAGGTCTTGTTGCTGGTGAAGGTCAGCTGCA ACCCGCGGT

GCTCCTCGTTCAGCCAGGTCTTGCATACGGCCGCCAGAGCTTCCACTTGGTCAGGCA GTAGTTTGA

AGTTCGCCTTTAGATCGTTATCCACGTGGTACTTGTCCATCAGCGCGCGCGCAGCCT CCATGCCCTT

CTCCCACGCAGACACGATCGGCACACTCAGCGGGTTCATCACCGTAATTTCACTTTC CGCTTCGCT

GGGCTCTTCCTCTTCCTCTTGCGTCCGCATACCACGCGCCACTGGGTCGTCTTCATT CAGCCGCCGC

ACTGTGCGCTTACCTCCTTTGCCATGCTTGATTAGCACCGGTGGGTTGCTGAAACCC ACCATTTGTA

GCGCCACATCTTCTCTTTCTTCCTCGCTGTCCACGATTACTTTCACAGGAGGTACAG CTATGACCAT

GATTACGGATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGT TACCCAACT

TAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCG CACCGATCG

CCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATAGGTCGCGCCGCACCGCGTCCG CGCTCGGG

GGTGGTTTCGCGCTGCTCCTCTTCCCGACTGGCCATTTCCTTCTCCTATAGGCAGAA AAAGATCATG

GAGTCAGTCGAGAAGAAGGACAGCCTAACCGCCCCCTCTGAGTTCGCCACCACCGCC TCCACCGA

TGCCGCCAACGCGCCTACCACCTTCCCCGTCGAGGCACCCCCGCTTGAGGAGGAGGA AGTGATTAT

CGAGCAGGACCCAGGTTTTGTAAGCGAAGACGACGAGGACCGCTCAGTACCAACAGA GGATAAA

AAGCAAGACCAGGACAACGCAGAGGCAAACGAGGAACAAGTCGGGCGGGGGGACGAA AGGCAT

GGCGACTACCTAGATGTGGGAGACGACGTGCTGTTGAAGCATCTGCAGCGCCAGTGC GCCATTAT

CTGCGACGCGTTGCAAGAGCGCAGCGATGTGCCCCTCGCCATAGCGGATGTCAGCCT TGCCTACGA

ACGCCACCTATTCTCACCGCGCGTACCCCCCAAACGCCAAGAAAACGGCACATGCGA GCCCAACC

CGCGCCTCAACTTCTACCCCGTATTTGCCGTGCCAGAGGTGCTTGCCACCTATCACA TCTTTTTCCA

AAACTGCAAGATACCCCTATCCTGCCGTGCCAACCGCAGCCGAGCGGACAAGCAGCT GGCCTTGC

GGCAGGGCGCTGTCATACCTGATATCGCCTCGCTCAACGAAGTGCCAAAAATCTTTG AGGGTCTTG

GACGCGACGAGAAGCGCGCGGCAAACGCTCTGCAACAGGAAAACAGCGAAAATGAAA GTCACTC

TGGAGTGTTGGTGGAACTCGAGGGTGACAACGCGCGCCTAGCCGTACTAAAACGCAG CATCGAGG

TCACCCACTTTGCCTACCCGGCACTTAACCTACCCCCCAAGGTCATGAGCACAGTCA TGAGTGAGC

TGATCGTGCGCCGTGCGCAGCCCCTGGAGAGGGATGCAAATTTGCAAGAACAAACAG AGGAGGGC

CTACCCGCAGTTGGCGACGAGCAGCTAGCGCGCTGGCTTCAAACGCGCGAGCCTGCC GACTTGGA

GGAGCGACGCAAACTAATGATGGCCGCAGTGCTCGTTACCGTGGAGCTTGAGTGCAT GCAGCGGT

TCTTTGCTGACCCGGAGATGCAGCGCAAGCTAGAGGAAACATTGCACTACACCTTTC GACAGGGCT

ACGTACGCCAGGCCTGCAAGATCTCCAACGTGGAGCTCTGCAACCTGGTCTCCTACC TTGGAATTT

TGCACGAAAACCGCCTTGGGCAAAACGTGCTTCATTCCACGCTCAAGGGCGAGGCGC GCCGCGAC

TACGTCCGCGACTGCGTTTACTTATTTCTATGCTACACCTGGCAGACGGCCATGGGC GTTTGGCAG

CAGTGCTTGGAGGAGTGCAACCTCAAGGAGCTGCAGAAACTGCTAAAGCAAAACTTG AAGGACCT

ATGGACGGCCTTCAACGAGCGCTCCGTGGCCGCGCACCTGGCGGACATCATTTTCCC CGAACGCCT

GCTTAAAACCCTGCAACAGGGTCTGCCAGACTTCACCAGTCAAAGCATGTTGCAGAA CTTTAGGA

ACTTTATCCTAGAGCGCTCAGGAATCTTGCCCGCCACCTGCTGTGCACTTCCTAGCG ACTTTGTGCC

C ATT A AGT ACCGCG A AT GCCCTCCGCCGCTTTGGGGCC ACTGCT ACCTTCTGC AGCT AGCC A ACT A

CCTTGCCTACCACTCTGACATAATGGAAGACGTGAGCGGTGACGGTCTACTGGAGTG TCACTGTCG

CTGCAACCTATGCACCCCGCACCGCTCCCTGGTTTGCAATTCGCAGCTGCTTAACGA AAGTCAAAT

TATCGGTACCTTTGAGCTGCAGGGTCCCTCGCCTGACGAAAAGTCCGCGGCTCCGGG GTTGAAACT

CACTCCGGGGCTGTGGACGTCGGCTTACCTTCGCAAATTTGTACCTGAGGACTACCA CGCCCACGA

GATTAGGTTCTACGAAGACCAATCCCGCCCGCCTAATGCGGAGCTTACCGCCTGCGT CATTACCCA

GGGCCACATTCTTGGCCAATTGCAAGCCATCAACAAAGCCCGCCAAGAGTTTCTGCT ACGAAAGG

GACGGGGGGTTTACTTGGACCCCCAGTCCGGCGAGGAGCTCAACCCAATCCCCCCGC CGCCGCAG

CCCTATCAGCAGCAGCCGCGGGCCCTTGCTTCCCAGGATGGCACCCAAAAAGAAGCT GCAGCTGC

CGCCGCCACCCACGGACGAGGAGGAATACTGGGACAGTCAGGCAGAGGAGGTTTTGG ACGAGGA

GGAGGAGGACATGATGGAAGACTGGGAGAGCCTAGACGAGGAAGCTTCCGAGGTCGA AGAGGTG

TCAGACGAAACACCGTCACCCTCGGTCGCATTCCCCTCGCCGGCGCCCCAGAAATCG GCAACCGGT TCCAGCATGGCTACAACCTCCGCTCCTCAGGCGCCGCCGGCACTGCCCGTTCGCCGACCC AACCGT

AGATGGGACACCACTGGAACCAGGGCCGGTAAGTCCAAGCAGCCGCCGCCGTTAGCC CAAGAGCA

ACAACAGCGCCAAGGCTACCGCTCATGGCGCGGGCACAAGAACGCCATAGTTGCTTG CTTGCAAG

ACTGTGGGGGCAACATCTCCTTCGCCCGCCGCTTTCTTCTCTACCATCACGGCGTGG CCTTCCCCCG

TAACATCCTGCATTACTACCGTCATCTCTACAGCCCATACTGCACCGGCGGCAGCGG CAGCAACAG

CAGCGGCCACACAGAAGCAAAGGCGACCGGATAGCAAGACTCTGACAAAGCCCAAGA AATCCAC

AGCGGCGGCAGCAGCAGGAGGAGGAGCGCTGCGTCTGGCGCCCAACGAACCCGTATC GACCCGC

G AGCTT AG A A AC AGG ATTTTTCCC ACTCTGT ATGCT AT ATTTC A AC AG AGC AGGGGCC A AG A AC A A

GAGCTGAAAATAAAAAACAGGTCTCTGCGATCCCTCACCCGCAGCTGCCTGTATCAC AAAAGCGA

AGATCAGCTTCGGCGCACGCTGGAAGACGCGGAGGCTCTCTTCAGTAAATACTGCGC GCTGACTCT

T AAGG ACT AGTTTCGCGCCCTTTCTC A A ATTT A AGCGCG A A A ACT ACGTC ATCTCC AGCGGCC AC A

CCCGGCGCCAGCACCTGTTGTCAGCGCCATTATGAGCAAGGAAATTCCCACGCCCTA CATGTGGAG

TTACCAGCCACAAATGGGACTTGCGGCTGGAGCTGCCCAAGACTACTCAACCCGAAT AAACTACA

TGAGCGCGGGACCCCACATGATATCCCGGGTCAACGGAATACGCGCCCACCGAAACC GAATTCTC

CTGG A AC AGGCGGCT ATT ACC ACC AC ACCTCGT A AT AACCTT A ATCCCCGT AGTTGGCCCGCTGCC

CTGGTGTACCAGGAAAGTCCCGCTCCCACCACTGTGGTACTTCCCAGAGACGCCCAG GCCGAAGTT

CAGATGACTAACTCAGGGGCGCAGCTTGCGGGCGGCTTTCGTCACAGGGTGCGGTCG CCCGGGCA

GGGTATAACTCACCTGACAATCAGAGGGCGAGGTATTCAGCTCAACGACGAGTCGGT GAGCTCCT

CGCTTGGTCTCCGTCCGGACGGGACATTTCAGATCGGCGGCGCCGGCCGCTCTTCAT TCACGCCTC

GTCAGGCAATCCTAACTCTGCAGACCTCGTCCTCTGAGCCGCGCTCTGGAGGCATTG GAACTCTGC

AATTTATTGAGGAGTTTGTGCCATCGGTCTACTTTAACCCCTTCTCGGGACCTCCCG GCCACTATCC

GGATCAATTTATTCCTAACTTTGACGCGGTAAAGGACTCGGCGGACGGCTACGACTG AATGTTAAG

TGGAGAGGCAGAGCAACTGCGCCTGAAACACCTGGTCCACTGTCGCCGCCACAAGTG CTTTGCCC

GCGACTCCGGTGAGTTTTGCTACTTTGAATTGCCCGAGGATCATATCGAGGGCCCGG CGCACGGCG

TCCGGCTTACCGCCCAGGGAGAGCTTGCCCGTAGCCTGATTCGGGAGTTTACCCAGC GCCCCCTGC

TAGTTGAGCGGGACAGGGGACCCTGTGTTCTCACTGTGATTTGCAACTGTCCTAACC CTGGATTAC

ATCAAGATCTTTGTTGCCATCTCTGTGCTGAGTATAATAAATACAGAAATTAAAATA TACTGGGGC

TCCT ATCGCC ATCCTGT AA ACGCC ACCGTCTTC ACCCGCCC A AGC A A ACC A AGGCG A ACCTT ACCT

GGTACTTTTAACATCTCTCCCTCTGTGATTTACAACAGTTTCAACCCAGACGGAGTG AGTCTACGA

GAGAACCTCTCCGAGCTCAGCTACTCCATCAGAAAAAACACCACCCTCCTTACCTGC CGGGAACGT

ACGAGTGCGTCACCGGCCGCTGCACCACACCTACCGCCTGACCGTAAACCAGACTTT TTCCGGACA

GACCTCAATAACTCTGTTTACCAGAACAGGAGGTGAGCTTAGAAAACCCTTAGGGTA TTAGGCCA

A AGGCGC AGCT ACTGTGGGGTTT ATG A AC A ATTC AAGC A ACTCT ACGGGCT ATTCT A ATTC AGGTT

TCTCTAGAAATGGACGGAATTATTACAGAGCAGCGCCTGCTAGAAAGACGCAGGGCA GCGGCCGA

GCAACAGCGCATGAATCAAGAGCTCCAAGACATGGTTAACTTGCACCAGTGCAAAAG GGGTATCT

TTTGTCTGGTAAAGCAGGCCAAAGTCACCTACGACAGTAATACCACCGGACACCGCC TTAGCTACA

AGTTGCCAACCAAGCGTCAGAAATTGGTGGTCATGGTGGGAGAAAAGCCCATTACCA TAACTCAG

CACTCGGTAGAAACCGAAGGCTGCATTCACTCACCTTGTCAAGGACCTGAGGATCTC TGCACCCTT

ATT A AG ACCCTGTGCGGTCTC A A AG ATCTT ATTCCCTTT A ACT A AT A A A A A A A A AT A AT A A AGC AT

C ACTT ACTT AA A ATC AGTT AGC A A ATTTCTGTCC AGTTT ATTC AGC AGC ACCTCCTTGCCCTCCTCC

CAGCTCTGGTATTGCAGCTTCCTCCTGGCTGCAAACTTTCTCCACAATCTAAATGGA ATGTCAGTTT

CCTCCTGTTCCTGTCCATCCGCACCCACTATCTTCATGTTGTTGCAGATGAAGCGCG CAAGACCGTC

TGAAGATACCTTCAACCCCGTGTATCCATATGACACGGAAACCGGTCCTCCAACTGT GCCTTTTCTT

ACTCCTCCCTTTGTATCCCCCAATGGGTTTCAAGAGAGTCCCCCTGGGGTACTCTCT TTGCGCCTAT

CCGAACCTCTAGTTACCTCCAATGGCATGCTTGCGCTCAAAATGGGCAACGGCCTCT CTCTGGACG

AGGCCGGC AACCTT ACCTCCCAAAATGTAACCACTGTGAGCCCACCTCTCAAAAAAACCAAGTCA

AACATAAACCTGGAAATATCTGCACCCCTCACAGTTACCTCAGAAGCCCTAACTGTG GCTGCCGCC

GCACCTCTAATGGTCGCGGGCAACACACTCACCATGCAATCACAGGCCCCGCTAACC GTGCACGA

CTCCAAACTTAGCATTGCCACCCAAGGACCCCTCACAGTGTCAGAAGGAAAGCTAGC CCTGCAAA

C ATC AGGCCCCCTC ACC ACC ACCG AT AGC AGT ACCCTT ACT ATC ACTGCCTC ACCCCCTCT A ACT A

CTGCCACTGGTAGCTTGGGCATTGACTTGAAAGAGCCCATTTATACACAAAATGGAA AACTAGGA

CTAAAGTACGGGGCTCCTTTGCATGTAACAGACGACCTAAACACTTTGACCGTAGCA ACTGGTCCA

GGTGTGACTATTAATAATACTTCCTTGCAAACTAAAGTTACTGGAGCCTTGGGTTTT GATTCACAA

GGC A AT ATGC A ACTT A ATGT AGC AGG AGG ACT A AGG ATTG ATTCTC A A A AC AG ACGCCTT AT ACTT

G ATGTT AGTT ATCCGTTTG ATGCTC A A A ACC A ACT A A ATCT A AG ACT AGG AC AGGGCCCTCTTTTT

AT A A ACTC AGCCC AC A ACTTGG AT ATT A ACT AC A AC A A AGGCCTTT ACTTGTTT AC AGCTTC A A AC

AATTCCAAAAAGCTTGAGGTTAACCTAAGCACTGCCAAGGGGTTGATGTTTGACGCT ACAGCCATA

GCCATTAATGCAGGAGATGGGCTTGAATTTGGTTCACCTAATGCACCAAACACAAAT CCCCTCAAA

ACAAAAATTGGCCATGGCCTAGAATTTGATTCAAACAAGGCTATGGTTCCTAAACTA GGAACTGG CCTTAGTTTTGACAGCACAGGTGCCATTACAGTAGGAAACAAAAATAATGATAAGCTAAC TTTGTG

GACCACACCAGCTCCATCTCCTAACTGTAGACTAAATGCAGAGAAAGATGCTAAACT CACTTTGGT

CTTAACAAAATGTGGCAGTCAAATACTTGCTACAGTTTCAGTTTTGGCTGTTAAAGG CAGTTTGGC

TCCAATATCTGGAACAGTTCAAAGTGCTCATCTTATTATAAGATTTGACGAAAATGG AGTGCTACT

AAACAATTCCTTCCTGGACCCAGAATATTGGAACTTTAGAAATGGAGATCTTACTGA AGGCACAGC

CT AT AC A A ACGCTGTTGG ATTT ATGCCT A ACCT ATC AGCTT ATCC A A A ATCTC ACGGT A A A ACTGC

C A A A AGT A AC ATTGTC AGTC A AGTTT ACTT A A ACGG AG AC A A A ACT A A ACCTGT AAC ACT A ACC A

TTACACTAAACGGTACACAGGAAACAGGAGACACAACTCCAAGTGCATACTCTATGT CATTTTCAT

GGGACTGGTCTGGCCACAACTACATTAATGAAATATTTGCCACATCCTCTTACACTT TTTCATACAT

TGCCCAAGAATAAAGAATCGTTTGTGTTATGTTTCAACGTGTTTATTTTTCAATTGC AGAAAATTTC

G A ATC ATTTTTC ATTC AGT AGT AT AGCCCC ACC ACC AC AT AGCTT AT AC AG ATC ACCGT ACCTT AAT

C A A ACTC AC AG A ACCCT AGT ATTC A ACCTGCC ACCTCCCTCCC A AC AC AC AG AGT AC AC AGTCCTT

TCTCCCCGGCTGGCCTT A AAA AGC ATC AT ATC ATGGGT A AC AG AC AT ATTCTT AGGTGTT AT ATTC

CACACGGTTTCCTGTCGAGCCAAACGCTCATCAGTGATATTAATAAACTCCCCGGGC AGCTCACTT

AAGTTCATGTCGCTGTCCAGCTGCTGAGCCACAGGCTGCTGTCCAACTTGCGGTTGC TTAACGGGC

GGCGAAGGAGAAGTCCACGCCTACATGGGGGTAGAGTCATAATCGTGCATCAGGATA GGGCGGTG

GTGCTGCAGCAGCGCGCGAATAAACTGCTGCCGCCGCCGCTCCGTCCTGCAGGAATA CAACATGG

CAGTGGTCTCCTCAGCGATGATTCGCACCGCCCGCAGCATAAGGCGCCTTGTCCTCC GGGCACAGC

AGCGCACCCTGATCTCACTTAAATCAGCACAGTAACTGCAGCACAGCACCACAATAT TGTTCAAAA

TCCCACAGTGCAAGGCGCTGTATCCAAAGCTCATGGCGGGGACCACAGAACCCACGT GGCCATCA

TACCACAAGCGCAGGTAGATTAAGTGGCGACCCCTCATAAACACGCTGGACATAAAC ATTACCTC

TTTTGGCATGTTGTAATTCACCACCTCCCGGTACCATATAAACCTCTGATTAAACAT GGCGCCATCC

ACCACCATCCTAAACCAGCTGGCCAAAACCTGCCCGCCGGCTATACACTGCAGGGAA CCGGGACT

GGAACAATGACAGTGGAGAGCCCAGGACTCGTAACCATGGATCATCATGCTCGTCAT GATATCAA

TGTTGGCACAACACAGGCACACGTGCATACACTTCCTCAGGATTACAAGCTCCTCCC GCGTTAGAA

CCATATCCCAGGGAACAACCCATTCCTGAATCAGCGTAAATCCCACACTGCAGGGAA GACCTCGC

ACGTAACTCACGTTGTGCATTGTCAAAGTGTTACATTCGGGCAGCAGCGGATGATCC TCCAGTATG

GTAGCGCGGGTTTCTGTCTCAAAAGGAGGTAGACGATCCCTACTGTACGGAGTGCGC CGAGACAA

CCGAGATCGTGTTGGTCGTAGTGTCATGCCAAATGGAACGCCGGACGTAGTCATATT TCCTGAAGC

AAAACCAGGTGCGGGCGTGACAAACAGATCTGCGTCTCCGGTCTCGCCGCTTAGATC GCTCTGTGT

AGT AGTTGT AGT AT ATCC ACTCTCTC A A AGC ATCC AGGCGCCCCCTGGCTTCGGGTTCT ATGT AAA

CTCCTTCATGCGCCGCTGCCCTGATAACATCCACCACCGCAGAATAAGCCACACCCA GCCAACCTA

CACATTCGTTCTGCGAGTCACACACGGGAGGAGCGGGAAGAGCTGGAAGAACCATGT TTTTTTTTT

TATTCCAAAAGATTATCCAAAACCTCAAAATGAAGATCTATTAAGTGAACGCGCTCC CCTCCGGTG

GCGTGGTCAAACTCTACAGCCAAAGAACAGATAATGGCATTTGTAAGATGTTGCACA ATGGCTTCC

AAAAGGCAAACGGCCCTCACGTCCAAGTGGACGTAAAGGCTAAACCCTTCAGGGTGA ATCTCCTC

T AT A A AC ATTCC AGC ACCTTC A ACC ATGCCC A A AT A ATTCTC ATCTCGCC ACCTTCTC A AT AT ATCT

CTAAGCAAATCCCGAATATTAAGTCCGGCCATTGTAAAAATCTGCTCCAGAGCGCCC TCCACCTTC

AGCCTCAAGCAGCGAATCATGATTGCAAAAATTCAGGTTCCTCACAGACCTGTATAA GATTCAAA

AGCGGAACATTAACAAAAATACCGCGATCCCGTAGGTCCCTTCGCAGGGCCAGCTGA ACATAATC

GTGCAGGTCTGCACGGACCAGCGCGGCCACTTCCCCGCCAGGAACCATGACAAAAGA ACCCACAC

TGATTATGACACGCATACTCGGAGCTATGCTAACCAGCGTAGCCCCGATGTAAGCTT GTTGCATGG

GCGGCGATATAAAATGCAAGGTGCTGCTCAAAAAATCAGGCAAAGCCTCGCGCAAAA AAGAAAG

CACATCGTAGTCATGCTCATGCAGATAAAGGCAGGTAAGCTCCGGAACCACCACAGA AAAAGACA

CCATTTTTCTCTCAAACATGTCTGCGGGTTTCTGCATAAACACAAAATAAAATAACA AAAAAACAT

TTA A AC ATT AG A AGCCTGTCTT AC A AC AGG A A A A AC A ACCCTT AT AAGC AT A AG ACGG ACT ACGG

CCATGCCGGCGTGACCGTAAAAAAACTGGTCACCGTGATTAAAAAGCACCACCGACA GCTCCTCG

GTCATGTCCGGAGTCATAATGTAAGACTCGGTAAACACATCAGGTTGATTCACATCG GTCAGTGCT

AAAAAGCGACCGAAATAGCCCGGGGGAATACATACCCGCAGGCGTAGAGACAACATT ACAGCCC

CCATAGGAGGTATAACAAAATTAATAGGAGAGAAAAACACATAAACACCTGAAAAAC CCTCCTGC

CTAGGCAAAATAGCACCCTCCCGCTCCAGAACAACATACAGCGCTTCCACAGCGGCA GCCATAAC

AGTC AGCCTT ACC AGT A A A A A AG A A A ACCT ATT AA A A A A AC ACC ACTCG AC ACGGC ACC AGCTC A

ATCAGTCACAGTGTAAAAAAGGGCCAAGTGCAGAGCGAGTATATATAGGACTAAAAA ATGACGTA

ACGGTTAAAGTCCACAAAAAACACCCAGAAAACCGCACGCGAACCTACGCCCAGAAA CGAAAGC

CAAAAAACCCACAACTTCCTCAAATCGTCACTTCCGTTTTCCCACGTTACGTCACTT CCCATTTTAA

G A A A ACT AC A ATTCCC A AC AC AT AC A AGTT ACTCCGCCCT A A A ACCT ACGTC ACCCGCCCCGTTCC

C ACGCCCCGCGCC ACGTC AC A A ACTCC ACCCCCTC ATT ATC AT ATTGGCTTC A ATCC A A A AT A AGG

TATATTATTGATGATGTTAATTAATTTAAATCCGCATGCGATATCGAGCTCTCCCGG GAATTCGGAT

CTGCGACGCGAGGCTGGATGGCCTTCCCCATTATGATTCTTCTCGCGTTTAAGGGCA CCAATAACT GCCTT A A A A A A ATT ACGCCCCGCCCTGCC ACTC ATCGC AGT ACTGTTGT A ATTC ATT A AGC ATTCT

GCCGACATGGAAGCCATCACAAACGGCATGATGAACCTGAATCGCCAGCGGCATCAG CACCTTGT

CGCCTTGCGTATAATATTTGCCCATGGTGAAAACGGGGGCGAAGAAGTTGTCCATAT TGGCCACGT

TTAAATCAAAACTGGTGAAACTCACCCAGGGATTGGCTGAGACGAAAAACATATTCT CAATAAAC

CCTTT AGGG A A AT AGGCC AGGTTTTC ACCGT A AC ACGCC AC ATCTTGCG A AT AT ATGTGT AG A A AC

TGCCGGAAATCGTCGTGGTATTCACTCCAGAGCGATGAAAACGTTTCAGTTTGCTCA TGGAAAACG

GTGTAACAAGGGTGAACACTATCCCATATCACCAGCTCACCGTCTTTCATTGCCATA CGGAATTCC

GGATGAGCATTCATCAGGCGGGCAAGAATGTGAATAAAGGCCGGATAAAACTTGTGC TTATTTTTC

TTT ACGGTCTTT A A A A AGGCCGT A AT ATCC AGCTG A ACGGTCTGGTT AT AGGT AC ATTG AGC A ACT

GACTGAAATGCCTCAAAATGTTCTTTACGATGCCATTGGGATATATCAACGGTGGTA TATCCAGTG

_{ATTTTTTTCTCCATTTTAGCTTCCTTAGCTCCTGAAAATCTCGATAACTCAAAAA ATACGCCCGGTA}

GTGATCTTATTTCATTATGGTGAAAGTTGGAACCTCTTACGTGCCGATCAACGTCTC ATTTTCGCCA

AAAGTTGGCCCAGGGCTTCCCGGTATCAACAGGGACACCAGGATTTATTTATTCTGC GAAGTGATC

TTCCGTCACAGGTATTTATTCGCGATAAGCTCATGGAGCGGCGTAACCGTCGCACAG GAAGGACA

GAGAAAGCGCGGATCTGGGAAGTGACGGACAGAACGGTCAGGACCTGGATTGGGGAG GCGGTTG

CCGCCGCTGCTGCTGACGGTGTGACGTTCTCTGTTCCGGTCACACCACATACGTTCC GCCATTCCTA

TGCGATGCACATGCTGTATGCCGGTATACCGCTGAAAGTTCTGCAAAGCCTGATGGG ACATAAGTC

CATCAGTTCAACGGAAGTCTACACGAAGGTTTTTGCGCTGGATGTGGCTGCCCGGCA CCGGGTGCA

GTTTGCGATGCCGGAGTCTGATGCGGTTGCGATGCTGAAACAATTATCCTGAGAATA AATGCCTTG

GCCTTTATATGGAAATGTGGAACTGAGTGGATATGCTGTTTTTGTCTGTTAAACAGA GAAGCTGGC

TGTTATCCACTGAGAAGCGAACGAAACAGTCGGGAAAATCTCCCATTATCGTAGAGA TCCGCATT

ATTAATCTCAGGAGCCTGTGTAGCGTTTATAGGAAGTAGTGTTCTGTCATGATGCCT GCAAGCGGT

AACGAAAACGATTTGAATATGCCTTCAGGAACAATAGAAATCTTCGTGCGGTGTTAC GTTGAAGTG

GAGCGGATTATGTCAGCAATGGACAGAACAACCTAATGAACACAGAACCATGATGTG GTCTGTCC

TTTTACAGCCAGTAGTGCTCGCCGCAGTCGAGCGACAGGGCGAAGCCCTCGAGTGAG CGAGGAAG

CACCAGGGAACAGCACTTATATATTCTGCTTACACACGATGCCTGAAAAAACTTCCC TTGGGGTTA

TCC ACTT ATCC ACGGGG AT ATTTTT AT A ATT ATTTTTTTT AT AGTTTTT AG ATCTTCTTTTTT AG AGC

GCCTTGTAGGCCTTTATCCATGCTGGTTCTAGAGAAGGTGTTGTGACAAATTGCCCT TTCAGTGTGA

CAAATCACCCTCAAATGACAGTCCTGTCTGTGACAAATTGCCCTTAACCCTGTGACA AATTGCCCT

CAGAAGAAGCTGTTTTTTCACAAAGTTATCCCTGCTTATTGACTCTTTTTTATTTAG TGTGACAATC

TAAAAACTTGTCACACTTCACATGGATCTGTCATGGCGGAAACAGCGGTTATCAATC ACAAGAAA

CGTAAAAATAGCCCGCGAATCGTCCAGTCAAACGACCTCACTGAGGCGGCATATAGT CTCTCCCG

GGATCAAAAACGTATGCTGTATCTGTTCGTTGACCAGATCAGAAAATCTGATGGCAC CCTACAGGA

ACATGACGGTATCTGCGAGATCCATGTTGCTAAATATGCTGAAATATTCGGATTGAC CTCTGCGGA

AGCCAGTAAGGATATACGGCAGGCATTGAAGAGTTTCGCGGGGAAGGAAGTGGTTTT TTATCGCC

CTGAAGAGGATGCCGGCGATGAAAAAGGCTATGAATCTTTTCCTTGGTTTATCAAAC GTGCGCACA

GTCC ATCC AG AGGGCTTT AC AGTGT AC AT ATC A ACCC AT ATCTC ATTCCCTTCTTT ATCGGGTT AC A

GAACCGGTTTACGCAGTTTCGGCTTAGTGAAACAAAAGAAATCACCAATCCGTATGC CATGCGTTT

ATACGAATCCCTGTGTCAGTATCGTAAGCCGGATGGCTCAGGCATCGTCTCTCTGAA AATCGACTG

GATCATAGAGCGTTACCAGCTGCCTCAAAGTTACCAGCGTATGCCTGACTTCCGCCG CCGCTTCCT

GCAGGTCTGTGTTAATGAGATCAACAGCAGAACTCCAATGCGCCTCTCATACATTGA GAAAAAGA

A AGGCCGCC AG ACG ACTC AT ATCGT ATTTTCCTTCCGCG AT ATC ACTTCC ATG ACG AC AGG AT AGT

CTGAGGGTTATCTGTCACAGATTTGAGGGTGGTTCGTCACATTTGTTCTGACCTACT GAGGGTAATT

TGTCACAGTTTTGCTGTTTCCTTCAGCCTGCATGGATTTTCTCATACTTTTTGAACT GTAATTTTTAA

GGAAGCCAAATTTGAGGGCAGTTTGTCACAGTTGATTTCCTTCTCTTTCCCTTCGTC ATGTGACCTG

ATATCGGGGGTTAGTTCGTCATCATTGATGAGGGTTGATTATCACAGTTTATTACTC TGAATTGGCT

ATCCGCGTGTGTACCTCTACCTGGAGTTTTTCCCACGGTGGATATTTCTTCTTGCGC TGAGCGTAAG

AGCTATCTGACAGAACAGTTCTTCTTTGCTTCCTCGCCAGTTCGCTCGCTATGCTCG GTTACACGGC

TGCGGCGAGCGCTAGTGATAATAAGTGACTGAGGTATGTGCTCTTCTTATCTCCTTT TGTAGTGTTG

CTCTTATTTTAAACAACTTTGCGGTTTTTTGATGACTTTGCGATTTTGTTGTTGCTT TGCAGTAAATT

GCAAGATTTAATAAAAAAACGCAAAGCAATGATTAAAGGATGTTCAGAATGAAACTC ATGGAAAC

ACTTAACCAGTGCATAAACGCTGGTCATGAAATGACGAAGGCTATCGCCATTGCACA GTTTAATGA

TGACAGCCCGGAAGCGAGGAAAATAACCCGGCGCTGGAGAATAGGTGAAGCAGCGGA TTTAGTT

GGGGTTTCTTCTCAGGCTATCAGAGATGCCGAGAAAGCAGGGCGACTACCGCACCCG GATATGGA

AATTCGAGGACGGGTTGAGCAACGTGTTGGTTATACAATTGAACAAATTAATCATAT GCGTGATGT

GTTTGGTACGCGATTGCGACGTGCTGAAGACGTATTTCCACCGGTGATCGGGGTTGC TGCCCATAA

AGGTGGCGTTTACAAAACCTCAGTTTCTGTTCATCTTGCTCAGGATCTGGCTCTGAA GGGGCTACG

TGTTTTGCTCGTGGAAGGTAACGACCCCCAGGGAACAGCCTCAATGTATCACGGATG GGTACCAG

ATCTTCATATTCATGCAGAAGACACTCTCCTGCCTTTCTATCTTGGGGAAAAGGACG ATGTCACTT ATGCAATAAAGCCCACTTGCTGGCCGGGGCTTGACATTATTCCTTCCTGTCTGGCTCTGC ACCGTAT

TGAAACTGAGTTAATGGGCAAATTTGATGAAGGTAAACTGCCCACCGATCCACACCT GATGCTCCG

ACTGGCCATTGAAACTGTTGCTCATGACTATGATGTCATAGTTATTGACAGCGCGCC TAACCTGGG

TATCGGCACGATTAATGTCGTATGTGCTGCTGATGTGCTGATTGTTCCCACGCCTGC TGAGTTGTTT

GACTACACCTCCGCACTGCAGTTTTTCGATATGCTTCGTGATCTGCTCAAGAACGTT GATCTTAAAG

GGTTCG AGCCTG ATGT ACGT ATTTTGCTT ACC A A AT AC AGC A AT AGT A ATGGCTCTC AGTCCCCGT

GGATGGAGGAGCAAATTCGGGATGCCTGGGGAAGCATGGTTCTAAAAAATGTTGTAC GTGAAACG

GATGAAGTTGGTAAAGGTCAGATCCGGATGAGAACTGTTTTTGAACAGGCCATTGAT CAACGCTCT

TCAACTGGTGCCTGGAGAAATGCTCTTTCTATTTGGGAACCTGTCTGCAATGAAATT TTCGATCGTC

TGATTAAACCACGCTGGGAGATTAGATAATGAAGCGTGCGCCTGTTATTCCAAAACA TACGCTCAA

TACTCAACCGGTTGAAGATACTTCGTTATCGACACCAGCTGCCCCGATGGTGGATTC GTTAATTGC

GCGCGTAGGAGTAATGGCTCGCGGTAATGCCATTACTTTGCCTGTATGTGGTCGGGA TGTGAAGTT

TACTCTTGAAGTGCTCCGGGGTGATAGTGTTGAGAAGACCTCTCGGGTATGGTCAGG TAATGAACG

TGACCAGGAGCTGCTTACTGAGGACGCACTGGATGATCTCATCCCTTCTTTTCTACT GACTGGTCA

ACAGACACCGGCGTTCGGTCGAAGAGTATCTGGTGTCATAGAAATTGCCGATGGGAG TCGCCGTC

GTAAAGCTGCTGCACTTACCGAAAGTGATTATCGTGTTCTGGTTGGCGAGCTGGATG ATGAGCAGA

TGGCTGCATTATCCAGATTGGGTAACGATTATCGCCCAACAAGTGCTTATGAACGTG GTCAGCGTT

ATGCAAGCCGATTGCAGAATGAATTTGCTGGAAATATTTCTGCGCTGGCTGATGCGG AAAATATTT

CACGTAAGATTATTACCCGCTGTATCAACACCGCCAAATTGCCTAAATCAGTTGTTG CTCTTTTTTC

TCACCCCGGTGAACTATCTGCCCGGTCAGGTGATGCACTTCAAAAAGCCTTTACAGA TAAAGAGG

AATTACTTAAGCAGCAGGCATCTAACCTTCATGAGCAGAAAAAAGCTGGGGTGATAT TTGAAGCT

G A AG A AGTT ATC ACTCTTTT A ACTTCTGTGCTT AA A ACGTC ATCTGC ATC A AG A ACT AGTTT A AGCT

CACGACATCAGTTTGCTCCTGGAGCGACAGTATTGTATAAGGGCGATAAAATGGTGC TTAACCTGG

ACAGGTCTCGTGTTCCAACTGAGTGTATAGAGAAAATTGAGGCCATTCTTAAGGAAC TTGAAAAG

CCAGCACCCTGATGCGACCACGTTTTAGTCTACGTTTATCTGTCTTTACTTAATGTC CTTTGTTACA

GGCCAGAAAGCATAACTGGCCTGAATATTCTCTCTGGGCCCACTGTTCCACTTGTAT CGTCGGTCT

GATAATCAGACTGGGACCACGGTCCCACTCGTATCGTCGGTCTGATTATTAGTCTGG GACCACGGT

CCC ACTCGT ATCGTCGGTCTG ATT ATT AGTCTGGG ACC ACGGTCCC ACTCGT ATCGTCGGTCTG AT A

ATCAGACTGGGACCACGGTCCCACTCGTATCGTCGGTCTGATTATTAGTCTGGGACC ATGGTCCCA

CTCGT ATCGTCGGTCTG ATT ATT AGTCTGGG ACC ACGGTCCC ACTCGT ATCGTCGGTCTG ATT ATT A

GTCTGGAACCACGGTCCCACTCGTATCGTCGGTCTGATTATTAGTCTGGGACCACGG TCCCACTCG

TATCGTCGGTCTGATTATTAGTCTGGGACCACGATCCCACTCGTGTTGTCGGTCTGA TTATCGGTCT

GGGACCACGGTCCCACTTGTATTGTCGATCAGACTATCAGCGTGAGACTACGATTCC ATCAATGCC

TGTCAAGGGCAAGTATTGACATGTCGTCGTAACCTGTAGAACGGAGTAACCTCGGTG TGCGGTTGT

ATGCCTGCTGTGGATTGCTGCTGTGTCCTGCTTATCCACAACATTTTGCGCACGGTT ATGTGGACAA

AATACCTGGTTACCCAGGCCGTGCCGGCACGTTAACCGGGCACATTTCCCCGAAAAG TGCCACCTG

ACGTCT A AG A A ACC ATT ATT ATC ATG AC ATT A ACCT AT AAA A AT AGGCGT ATC ACG AGGCCCTTTC

GTCTTC A AG A ATTGG ATCCG A ATTCCCGGG AG AGCTCG AT ATCGC ATGCGG ATTT AA ATT A ATT A A

* C1B (SEQ ID NO: 83)

CATCATCAATAATATACCTTATTTTGGATTGAAGCCAATATGATAATGAGGGGGTGGAGT TTGTGA

CGTGGCGCGGGGCGTGGGAACGGGGCGGGTGACGTAGTAGTGTGGCGGAAGTGTGAT GTTGCAAG

TGTGGCGGAACACATGTAAGCGACGGATGTGGCAAAAGTGACGTTTTTGGTGTGCGC CGGTGTAC

ACAGGAAGTGACAATTTTCGCGCGGTTTTAGGCGGATGTTGTAGTAAATTTGGGCGT AACCGAGTA

AGATTTGGCCATTTTCGCGGGAAAACTGAATAAGAGGAAGTGAAATCTGAATAATTT TGTGTTACT

CATAGCGCGTAATATTTGTCTAGGGCCGCGGGGACTTTGACCGTTTACGTGGAGACT CGCCCAGGT

_{GTTTTTCTC AGGTGTTTTCCGCGTTCCGGGTC} A A _AGTTGGCGTTTT ATT ATT AT AGT _{C AGTCG} A AG _C

TTGGATCCGGTACCTCTAGAATTCTCGAGCGGCCGCTAGCGACATCGGATCTCCCGA TCCCCTATG

GTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGTATCTGCTCCC TGCTTGTGTG

TTGGAGGTCGCTGAGTAGTGCGCGAGCAAAATTTAAGCTACAACAAGGCAAGGCTTG ACCGACAA

TTGCATGAAGAATCTGCTTAGGGTTAGGCGTTTTGCGCTGCTTCGCGATGTACGGGC CAGATATAC

GCGTTG AC ATTG ATT ATTG ACT AGTT ATT AAT AGT A ATC A ATT ACGGGGTC ATT AGTTC AT AGCCC

ATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCC CAACGACCC

CCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTT CCATTGACG

TCAATGGGTGGACTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCA TATGCCAAG

TACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTA CATGACCTT

ATGGG ACTTTCCTACTTGGCAGT ACATCT ACGT ATT AGTCATCGCT ATT ACCATGGTGATGCGGTTT TGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCAC CCCATT

GACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGT AACAACTCC

GCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGA GCTCTCTG

GCT A ACT AG AG A ACCC ACTGCTT ACTGGCTT ATCGA A ATG AG ACCC A AGCTGGCT AGTT A AGCT AT

CAACAAGTTTGTACAAAAAAGCAGGCTTTAAAGGAACCAATTCAGTCGACTGGATCC GGTACCAC

CATGTTCCTGAACTGCTGCCCAGGTTGCTGTATGGAGCCTGAATTCACCATGGTGAG CAAGGGCGA

GGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGG CCACAAGT

TCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGT TCATCTGC

ACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTGGGGC GTGCAGTGC

TTCGCCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCC GAAGGCTAC

GTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAG GTGAAGTT

CGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAAC

ATCCTGGGGCACAAGCTGGAGTACAACGCCATCAGCGACAACGTCTATATCACCGCC GACAAGCA

GAAGAACGGCATCAAGGCCAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGT GCAGCTCG

CCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACA ACCACTAC

CTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTC CTGCTGGA

GTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAGGTCGACTA TCCGTACGA

CGT ACC AG ACT ACGC AT A ACCGCGGCCGC ACTCG AG AT ATCT AG ACCC AGCTTTCTTGT AC A A AGT

GGTTGATCTAGAGGGCCCGCGGTTCGAAGGTAAGCCTATCCCTAACCCTCTCCTCGG TCTCGATTC

TACGCGTACCGGTTAGTAATGAGTTTAAACGGGGGAGGCTAACTGAAACACGGAAGG AGACAATA

CCGGAAGGAACCCGCGCTATGACGGCAATAAAAAGACAGAATAAAACGCACGGGTGT TGGGTCG

TTTGTTCATAAACGCGGGGTTCGGTCCCAGGGCTGGCACTCTGTCGATACCCCACCG AGACCCCAT

TGGGGCCAATACGCCCGCGTTTCTTCCTTTTCCCCACCCCACCCCCCAAGTTCGGGT GAAGGCCCA

GGGCTCGCAGCCAACGTCGGGGCGGCAGGCCCTGCCATAGCAGATCCGATTCGACAG ATCACTGA

AATGTGTGGGCGTGGCTTAAGGGTGGGAAAGAATATATAAGGTGGGGGTCTTATGTA GTTTTGTAT

CTGTTTTGCAGCAGCCGCCGCCGCCATGAGCACCAACTCGTTTGATGGAAGCATTGT GAGCTCATA

TTTGACAACGCGCATGCCCCCATGGGCCGGGGTGCGTCAGAATGTGATGGGCTCCAG CATTGATG

GTCGCCCCGTCCTGCCCGCAAACTCTACTACCTTGACCTACGAGACCGTGTCTGGAA CGCCGTTGG

AGACTGCAGCCTCCGCCGCCGCTTCAGCCGCTGCAGCCACCGCCCGCGGGATTGTGA CTGACTTTG

CTTTCCTGAGCCCGCTTGCAAGCAGTGCAGCTTCCCGTTCATCCGCCCGCGATGACA AGTTGACGG

CTCTTTTGGCACAATTGGATTCTTTGACCCGGGAACTTAATGTCGTTTCTCAGCAGC TGTTGGATCT

GCGCCAGCAGGTTTCTGCCCTGAAGGCTTCCTCCCCTCCCAATGCGGTTTAAAACAT AAATAAAAA

ACCAGACTCTGTTTGGATTTGGATCAAGCAAGTGTCTTGCTGTCTTTATTTAGGGGT TTTGCGCGCG

CGGTAGGCCCGGGACCAGCGGTCTCGGTCGTTGAGGGTCCTGTGTATTTTTTCCAGG ACGTGGTAA

AGGTGACTCTGGATGTTCAGATACATGGGCATAAGCCCGTCTCTGGGGTGGAGGTAG CACCACTG

CAGAGCTTCATGCTGCGGGGTGGTGTTGTAGATGATCCAGTCGTAGCAGGAGCGCTG GGCGTGGT

GCCTAAAAATGTCTTTCAGTAGCAAGCTGATTGCCAGGGGCAGGCCCTTGGTGTAAG TGTTTACAA

AGCGGTTAAGCTGGGATGGGTGCATACGTGGGGATATGAGATGCATCTTGGACTGTA TTTTTAGGT

TGGCTATGTTCCCAGCCATATCCCTCCGGGGATTCATGTTGTGCAGAACCACCAGCA CAGTGTATC

CGGTGCACTTGGGAAATTTGTCATGTAGCTTAGAAGGAAATGCGTGGAAGAACTTGG AGACGCCC

TTGTGACCTCCAAGATTTTCCATGCATTCGTCCATAATGATGGCAATGGGCCCACGG GCGGCGGCC

TGGGCGAAGATATTTCTGGGATCACTAACGTCATAGTTGTGTTCCAGGATGAGATCG TCATAGGCC

_{ATTTTTACAAAGCGCGGGCGGAGGGTGCCAGACTGCGGTATAATGGTTCCATCCG GCCCAGGGGC}

GTAGTTACCCTCACAGATTTGCATTTCCCACGCTTTGAGTTCAGATGGGGGGATCAT GTCTACCTGC

GGGGCGATGAAGAAAACGGTTTCCGGGGTAGGGGAGATCAGCTGGGAAGAAAGCAGG TTCCTGA

GCAGCTGCGACTTACCGCAGCCGGTGGGCCCGTAAATCACACCTATTACCGGCTGCA ACTGGTAGT

TAAGAGAGCTGCAGCTGCCGTCATCCCTGAGCAGGGGGGCCACTTCGTTAAGCATGT CCCTGACTC

GCATGTTTTCCCTGACCAAATCCGCCAGAAGGCGCTCGCCGCCCAGCGATAGCAGTT CTTGCAAGG

AAGCAAAGTTTTTCAACGGTTTGAGACCGTCCGCCGTAGGCATGCTTTTGAGCGTTT GACCAAGCA

GTTCCAGGCGGTCCCACAGCTCGGTCACCTGCTCTACGGCATCTCGATCCAGCATAT CTCCTCGTTT

CGCGGGTTGGGGCGGCTTTCGCTGTACGGCAGTAGTCGGTGCTCGTCCAGACGGGCC AGGGTCAT

GTCTTTCCACGGGCGCAGGGTCCTCGTCAGCGTAGTCTGGGTCACGGTGAAGGGGTG CGCTCCGGG

CTGCGCGCTGGCCAGGGTGCGCTTGAGGCTGGTCCTGCTGGTGCTGAAGCGCTGCCG GTCTTCGCC

CTGCGCGTCGGCCAGGTAGCATTTGACCATGGTGTCATAGTCCAGCCCCTCCGCGGC GTGGCCCTT

GGCGCGCAGCTTGCCCTTGGAGGAGGCGCCGCACGAGGGGCAGTGCAGACTTTTGAG GGCGTAGA

GCTTGGGCGCGAGAAATACCGATTCCGGGGAGTAGGCATCCGCGCCGCAGGCCCCGC AGACGGTC

TCGCATTCCACGAGCCAGGTGAGCTCTGGCCGTTCGGGGTCAAAAACCAGGTTTCCC CCATGCTTT

TTGATGCGTTTCTTACCTCTGGTTTCCATGAGCCGGTGTCCACGCTCGGTGACGAAA AGGCTGTCC

GTGTCCCCGTATACAGACTTGAGAGGCCTGTCCTCGAGCGGTGTTCCGCGGTCCTCC TCGTATAGA AACTCGGACCACTCTGAGACAAAGGCTCGCGTCCAGGCCAGCACGAAGGAGGCTAAGTGG GAGG

GGTAGCGGTCGTTGTCCACTAGGGGGTCCACTCGCTCCAGGGTGTGAAGACACATGT CGCCCTCTT

CGGCATCAAGGAAGGTGATTGGTTTGTAGGTGTAGGCCACGTGACCGGGTGTTCCTG AAGGGGGG

CTATAAAAGGGGGTGGGGGCGCGTTCGTCCTCACTCTCTTCCGCATCGCTGTCTGCG AGGGCCAGC

TGTTGGGGTGAGTACTCCCTCTGAAAAGCGGGCATGACTTCTGCGCTAAGATTGTCA GTTTCCAAA

AACGAGGAGGATTTGATATTCACCTGGCCCGCGGTGATGCCTTTGAGGGTGGCCGCA TCCATCTGG

TCAGAAAAGACAATCTTTTTGTTGTCAAGCTTGGTGGCAAACGACCCGTAGAGGGCG TTGGACAG

CAACTTGGCGATGGAGCGCAGGGTTTGGTTTTTGTCGCGATCGGCGCGCTCCTTGGC CGCGATGTT

TAGCTGCACGTATTCGCGCGCAACGCACCGCCATTCGGGAAAGACGGTGGTGCGCTC GTCGGGCA

CCAGGTGCACGCGCCAACCGCGGTTGTGCAGGGTGACAAGGTCAACGCTGGTGGCTA CCTCTCCG

CGTAGGCGCTCGTTGGTCCAGCAGAGGCGGCCGCCCTTGCGCGAGCAGAATGGCGGT AGGGGGTC

TAGCTGCGTCTCGTCCGGGGGGTCTGCGTCCACGGTAAAGACCCCGGGCAGCAGGCG CGCGTCGA

AGTAGTCTATCTTGCATCCTTGCAAGTCTAGCGCCTGCTGCCATGCGCGGGCGGCAA GCGCGCGCT

CGTATGGGTTGAGTGGGGGACCCCATGGCATGGGGTGGGTGAGCGCGGAGGCGTACA TGCCGCAA

ATGTCGTAAACGTAGAGGGGCTCTCTGAGTATTCCAAGATATGTAGGGTAGCATCTT CCACCGCGG

ATGCTGGCGCGCACGTAATCGTATAGTTCGTGCGAGGGAGCGAGGAGGTCGGGACCG AGGTTGCT

ACGGGCGGGCTGCTCTGCTCGGAAGACTATCTGCCTGAAGATGGCATGTGAGTTGGA TGATATGGT

TGGACGCTGGAAGACGTTGAAGCTGGCGTCTGTGAGACCTACCGCGTCACGCACGAA GGAGGCGT

AGGAGTCGCGCAGCTTGTTGACCAGCTCGGCGGTGACCTGCACGTCTAGGGCGCAGT AGTCCAGG

GTTTCCTTGATGATGTCATACTTATCCTGTCCCTTTTTTTTCCACAGCTCGCGGTTG AGGACAAACT

CTTCGCGGTCTTTCCAGTACTCTTGGATCGGAAACCCGTCGGCCTCCGAACGGTAAG AGCCTAGCA

TGTAGAACTGGTTGACGGCCTGGTAGGCGCAGCATCCCTTTTCTACGGGTAGCGCGT ATGCCTGCG

CGGCCTTCCGGAGCGAGGTGTGGGTGAGCGCAAAGGTGTCCCTGACCATGACCAGCA TGAAGGGC

ACGAGCTGCTTCCCAAAGGCCCCCATCCAAGTATAGGTCTCTACATCGTAGGTGACA AAGAGACG

CTCGGTGCGAGGATGCGAGCCGATCGGGAAGAACTGGATCTCCCGCCACCAATTGGA GGAGTGGC

TATTGATGTGGTGAAAGTAGAAGTCCCTGCGACGGGCCGAACACTCGTGCTGGCTTT TGTAAAAAC

GTGCGCAGTACTGGCAGCGGTGCACGGGCTGTACATCCTGCACGAGGTTGACCTGAC GACCGCGC

ACAAGGAAGCAGAGTGGGAATTTGAGCCCCTCGCCTGGCGGGTTTGGCTGGTGGTCT TCTACTTCG

GCTGCTTGTCCTTGACCGTCTGGCTGCTCGAGGGGAGTTACGGTGGATCGGACCACC ACGCCGCGC

GAGCCCAAAGTCCAGATGTCCGCGCGCGGCGGTCGGAGCTTGATGACAACATCGCGC AGATGGGA

GCTGTCCATGGTCTGGAGCTCCCGCGGCGTCAGGTCAGGCGGGAGCTCCTGCAGGTT TACCTCGCA

TAGACGGGTCAGGGCGCGGGCTAGATCCAGGTGATACCTAATTTCCAGGGGCTGGTT GGTGGCGG

CGTCGATGGCTTGCAAGAGGCCGCATCCCCGCGGCGCGACTACGGTACCGCGCGGCG GGCGGTGG

GCCGCGGGGGTGTCCTTGGATGATGCATCTAAAAGCGGTGACGCGGGCGAGCCCCCG GAGGTAGG

GGGGGCTCCGGACCCGCCGGGAGAGGGGGCAGGGGCACGTCGGCGCCGCGCGCGGGC AGGAGCT

GGTGCTGCGCGCGTAGGTTGCTGGCGAACGCGACGACGCGGCGGTTGATCTCCTGAA TCTGGCGC

CTCTGCGTGAAGACGACGGGCCCGGTGAGCTTGAACCTGAAAGAGAGTTCGACAGAA TCAATTTC

GGTGTCGTTGACGGCGGCCTGGCGCAAAATCTCCTGCACGTCTCCTGAGTTGTCTTG ATAGGCGAT

CTCGGCCATGAACTGCTCGATCTCTTCCTCCTGGAGATCTCCGCGTCCGGCTCGCTC CACGGTGGC

GGCGAGGTCGTTGGAAATGCGGGCCATGAGCTGCGAGAAGGCGTTGAGGCCTCCCTC GTTCCAGA

CGCGGCTGTAGACCACGCCCCCTTCGGCATCGCGGGCGCGCATGACCACCTGCGCGA GATTGAGC

TCCACGTGCCGGGCGAAGACGGCGTAGTTTCGCAGGCGCTGAAAGAGGTAGTTGAGG GTGGTGGC

GGTGTGTTCTGCCACGAAGAAGTACATAACCCAGCGTCGCAACGTGGATTCGTTGAT ATCCCCCAA

GGCCTCAAGGCGCTCCATGGCCTCGTAGAAGTCCACGGCGAAGTTGAAAAACTGGGA GTTGCGCG

CCGACACGGTTAACTCCTCCTCCAGAAGACGGATGAGCTCGGCGACAGTGTCGCGCA CCTCGCGCT

CAAAGGCTACAGGGGCCTCTTCTTCTTCTTCAATCTCCTCTTCCATAAGGGCCTCCC CTTCTTCTTCT

TCTGGCGGCGGTGGGGGAGGGGGGACACGGCGGCGACGACGGCGCACCGGGAGGCGG TCGACAA

AGCGCTCGATCATCTCCCCGCGGCGACGGCGCATGGTCTCGGTGACGGCGCGGCCGT TCTCGCGGG

GGCGCAGTTGGAAGACGCCGCCCGTCATGTCCCGGTTATGGGTTGGCGGGGGGCTGC CATGCGGC

AGGGATACGGCGCTAACGATGCATCTCAACAATTGTTGTGTAGGTACTCCGCCGCCG AGGGACCT

GAGCGAGTCCGCATCGACCGGATCGGAAAACCTCTCGAGAAAGGCGTCTAACCAGTC ACAGTCGC

AAGGTAGGCTGAGCACCGTGGCGGGCGGCAGCGGGCGGCGGTCGGGGTTGTTTCTGG CGGAGGTG

CTGCTGATGATGTAATTAAAGTAGGCGGTCTTGAGACGGCGGATGGTCGACAGAAGC ACCATGTC

CTTGGGTCCGGCCTGCTGAATGCGCAGGCGGTCGGCCATGCCCCAGGCTTCGTTTTG ACATCGGCG

CAGGTCTTTGTAGTAGTCTTGCATGAGCCTTTCTACCGGCACTTCTTCTTCTCCTTC CTCTTGTCCTG

CATCTCTTGCATCTATCGCTGCGGCGGCGGCGGAGTTTGGCCGTAGGTGGCGCCCTC TTCCTCCCAT

GCGTGTGACCCCGAAGCCCCTCATCGGCTGAAGCAGGGCTAGGTCGGCGACAACGCG CTCGGCTA

ATATGGCCTGCTGCACCTGCGTGAGGGTAGACTGGAAGTCATCCATGTCCACAAAGC GGTGGTAT

GCGCCCGTGTTGATGGTGTAAGTGCAGTTGGCCATAACGGACCAGTTAACGGTCTGG TGACCCGGC TGCGAGAGCTCGGTGTACCTGAGACGCGAGTAAGCCCTCGAGTCAAATACGTAGTCGTTG CAAGT

CCGCACCAGGTACTGGTATCCCACCAAAAAGTGCGGCGGCGGCTGGCGGTAGAGGGG CCAGCGTA

GGGTGGCCGGGGCTCCGGGGGCGAGATCTTCCAACATAAGGCGATGATATCCGTAGA TGTACCTG

GACATCCAGGTGATGCCGGCGGCGGTGGTGGAGGCGCGCGGAAAGTCGCGGACGCGG TTCCAGAT

GTTGCGCAGCGGCAAAAAGTGCTCCATGGTCGGGACGCTCTGGCCGGTCAGGCGCGC GCAATCGT

TGACGCTCTAGACCGTGCAAAAGGAGAGCCTGTAAGCGGGCACTCTTCCGTGGTCTG GTGGATAA

ATTCGCAAGGGTATCATGGCGGACGACCGGGGTTCGAGCCCCGTATCCGGCCGTCCG CCGTGATCC

ATGCGGTTACCGCCCGCGTGTCGAACCCAGGTGTGCGACGTCAGACAACGGGGGAGT GCTCCTTTT

GGCTTCCTTCCAGGCGCGGCGGCTGCTGCGCTAGCTTTTTTGGCCACTGGCCGCGCG CAGCGTAAG

CGGTTAGGCTGGAAAGCGAAAGCATTAAGTGGCTCGCTCCCTGTAGCCGGAGGGTTA TTTTCCAAG

GGTTGAGTCGCGGGACCCCCGGTTCGAGTCTCGGACCGGCCGGACTGCGGCGAACGG GGGTTTGC

CTCCCCGTCATGCAAGACCCCGCTTGCAAATTCCTCCGGAAACAGGGACGAGCCCCT TTTTTGCTT

TTCCCAGATGCATCCGGTGCTGCGGCAGATGCGCCCCCCTCCTCAGCAGCGGCAAGA GCAAGAGC

AGCGGCAGACATGCAGGGCACCCTCCCCTCCTCCTACCGCGTCAGGAGGGGCGACAT CCGCGGTT

GACGCGGCAGCAGATGGTGATTACGAACCCCCGCGGCGCCGGGCCCGGCACTACCTG GACTTGGA

GGAGGGCGAGGGCCTGGCGCGGCTAGGAGCGCCCTCTCCTGAGCGGCACCCAAGGGT GCAGCTGA

AGCGTGATACGCGTGAGGCGTACGTGCCGCGGCAGAACCTGTTTCGCGACCGCGAGG GAGAGGAG

CCCGAGGAGATGCGGGATCGAAAGTTCCACGCAGGGCGCGAGCTGCGGCATGGCCTG AATCGCGA

GCGGTTGCTGCGCGAGGAGGACTTTGAGCCCGACGCGCGAACCGGGATTAGTCCCGC GCGCGCAC

ACGTGGCGGCCGCCGACCTGGTAACCGCATACGAGCAGACGGTGAACCAGGAGATTA ACTTTCAA

AAAAGCTTTAACAACCACGTGCGTACGCTTGTGGCGCGCGAGGAGGTGGCTATAGGA CTGATGCA

TCTGTGGGACTTTGTAAGCGCGCTGGAGCAAAACCCAAATAGCAAGCCGCTCATGGC GCAGCTGT

TCCTTATAGTGCAGCACAGCAGGGACAACGAGGCATTCAGGGATGCGCTGCTAAACA TAGTAGAG

CCCGAGGGCCGCTGGCTGCTCGATTTGATAAACATCCTGCAGAGCATAGTGGTGCAG GAGCGCAG

CTTGAGCCTGGCTGACAAGGTGGCCGCCATCAACTATTCCATGCTTAGCCTGGGCAA GTTTTACGC

CCGCAAGATATACCATACCCCTTACGTTCCCATAGACAAGGAGGTAAAGATCGAGGG GTTCTACA

TGCGCATGGCGCTGAAGGTGCTTACCTTGAGCGACGACCTGGGCGTTTATCGCAACG AGCGCATCC

ACAAGGCCGTGAGCGTGAGCCGGCGGCGCGAGCTCAGCGACCGCGAGCTGATGCACA GCCTGCAA

AGGGCCCTGGCTGGCACGGGCAGCGGCGATAGAGAGGCCGAGTCCTACTTTGACGCG GGCGCTGA

CCTGCGCTGGGCCCCAAGCCGACGCGCCCTGGAGGCAGCTGGGGCCGGACCTGGGCT GGCGGTGG

CACCCGCGCGCGCTGGCAACGTCGGCGGCGTGGAGGAATATGACGAGGACGATGAGT ACGAGCC

AGAGGACGGCGAGTACTAAGCGGTGATGTTTCTGATCAGATGATGCAAGACGCAACG GACCCGGC

GGTGCGGGCGGCGCTGCAGAGCCAGCCGTCCGGCCTTAACTCCACGGACGACTGGCG CCAGGTCA

TGGACCGCATCATGTCGCTGACTGCGCGCAATCCTGACGCGTTCCGGCAGCAGCCGC AGGCCAAC

CGGCTCTCCGCAATTCTGGAAGCGGTGGTCCCGGCGCGCGCAAACCCCACGCACGAG AAGGTGCT

GGCGATCGTAAACGCGCTGGCCGAAAACAGGGCCATCCGGCCCGACGAGGCCGGCCT GGTCTACG

ACGCGCTGCTTCAGCGCGTGGCTCGTTACAACAGCGGCAACGTGCAGACCAACCTGG ACCGGCTG

GTGGGGGATGTGCGCGAGGCCGTGGCGCAGCGTGAGCGCGCGCAGCAGCAGGGCAAC CTGGGCT

CCATGGTTGCACTAAACGCCTTCCTGAGTACACAGCCCGCCAACGTGCCGCGGGGAC AGGAGGAC

TACACCAACTTTGTGAGCGCACTGCGGCTAATGGTGACTGAGACACCGCAAAGTGAG GTGTACCA

GTCTGGGCCAGACTATTTTTTCCAGACCAGTAGACAAGGCCTGCAGACCGTAAACCT GAGCCAGG

CTTTCAAAAACTTGCAGGGGCTGTGGGGGGTGCGGGCTCCCACAGGCGACCGCGCGA CCGTGTCT

AGCTTGCTGACGCCCAACTCGCGCCTGTTGCTGCTGCTAATAGCGCCCTTCACGGAC AGTGGCAGC

GTGTCCCGGGACACATACCTAGGTCACTTGCTGACACTGTACCGCGAGGCCATAGGT CAGGCGCAT

GTGGACGAGCATACTTTCCAGGAGATTACAAGTGTCAGCCGCGCGCTGGGGCAGGAG GACACGGG

CAGCCTGGAGGCAACCCTAAACTACCTGCTGACCAACCGGCGGCAGAAGATCCCCTC GTTGCACA

GTTTAAACAGCGAGGAGGAGCGCATTTTGCGCTACGTGCAGCAGAGCGTGAGCCTTA ACCTGATG

CGCGACGGGGTAACGCCCAGCGTGGCGCTGGACATGACCGCGCGCAACATGGAACCG GGCATGTA

TGCCTCAAACCGGCCGTTTATCAACCGCCTAATGGACTACTTGCATCGCGCGGCCGC CGTGAACCC

CGAGTATTTCACCAATGCCATCTTGAACCCGCACTGGCTACCGCCCCCTGGTTTCTA CACCGGGGG

ATTCGAGGTGCCCGAGGGTAACGATGGATTCCTCTGGGACGACATAGACGACAGCGT GTTTTCCCC

GCAACCGCAGACCCTGCTAGAGTTGCAACAGCGCGAGCAGGCAGAGGCGGCGCTGCG AAAGGAA

AGCTTCCGCAGGCCAAGCAGCTTGTCCGATCTAGGCGCTGCGGCCCCGCGGTCAGAT GCTAGTAGC

CCATTTCCAAGCTTGATAGGGTCTCTTACCAGCACTCGCACCACCCGCCCGCGCCTG CTGGGCGAG

GAGGAGTACCTAAACAACTCGCTGCTGCAGCCGCAGCGCGAAAAAAACCTGCCTCCG GCATTTCC

CAACAACGGGATAGAGAGCCTAGTGGACAAGATGAGTAGATGGAAGACGTACGCGCA GGAGCAC

AGGGACGTGCCAGGCCCGCGCCCGCCCACCCGTCGTCAAAGGCACGACCGTCAGCGG GGTCTGGT

GTGGGAGGACGATGACTCGGCAGACGACAGCAGCGTCCTGGATTTGGGAGGGAGTGG CAACCCGT

TTGCGCACCTTCGCCCCAGGCTGGGGAGAATGTTTTAAAAAAAAAAAAAGCATGATG CAAAATAA AAAACTCACCAAGGCCATGGCACCGAGCGTTGGTTTTCTTGTATTCCCCTTAGTATGCGG CGCGCG

GCGATGTATGAGGAAGGTCCTCCTCCCTCCTACGAGAGTGTGGTGAGCGCGGCGCCA GTGGCGGC

GGCGCTGGGTTCTCCCTTCGATGCTCCCCTGGACCCGCCGTTTGTGCCTCCGCGGTA CCTGCGGCCT

ACCGGGGGGAGAAACAGCATCCGTTACTCTGAGTTGGCACCCCTATTCGACACCACC CGTGTGTAC

CTGGTGGACAACAAGTCAACGGATGTGGCATCCCTGAACTACCAGAACGACCACAGC AACTTTCT

GACCACGGTCATTCAAAACAATGACTACAGCCCGGGGGAGGCAAGCACACAGACCAT CAATCTTG

ACGACCGGTCGCACTGGGGCGGCGACCTGAAAACCATCCTGCATACCAACATGCCAA ATGTGAAC

GAGTTCATGTTTACCAATAAGTTTAAGGCGCGGGTGATGGTGTCGCGCTTGCCTACT AAGGACAAT

CAGGTGGAGCTGAAATACGAGTGGGTGGAGTTCACGCTGCCCGAGGGCAACTACTCC GAGACCAT

GACCATAGACCTTATGAACAACGCGATCGTGGAGCACTACTTGAAAGTGGGCAGACA GAACGGGG

TTCTGGAAAGCGACATCGGGGTAAAGTTTGACACCCGCAACTTCAGACTGGGGTTTG ACCCCGTCA

CTGGTCTTGTCATGCCTGGGGTATATACAAACGAAGCCTTCCATCCAGACATCATTT TGCTGCCAG

GATGCGGGGTGGACTTCACCCACAGCCGCCTGAGCAACTTGTTGGGCATCCGCAAGC GGCAACCC

TTCCAGGAGGGCTTTAGGATCACCTACGATGATCTGGAGGGTGGTAACATTCCCGCA CTGTTGGAT

GTGGACGCCTACCAGGCGAGCTTGAAAGATGACACCGAACAGGGCGGGGGTGGCGCA GGCGGCA

GCAACAGCAGTGGCAGCGGCGCGGAAGAGAACTCCAACGCGGCAGCCGCGGCAATGC AGCCGGT

GGAGGACATGAACGATCATGCCATTCGCGGCGACACCTTTGCCACACGGGCTGAGGA GAAGCGCG

CTGAGGCCGAAGCAGCGGCCGAAGCTGCCGCCCCCGCTGCGCAACCCGAGGTCGAGA AGCCTCAG

AAGAAACCGGTGATCAAACCCCTGACAGAGGACAGCAAGAAACGCAGTTACAACCTA ATAAGCA

ATGACAGCACCTTCACCCAGTACCGCAGCTGGTACCTTGCATACAACTACGGCGACC CTCAGACCG

GAATCCGCTCATGGACCCTGCTTTGCACTCCTGACGTAACCTGCGGCTCGGAGCAGG TCTACTGGT

CGTTGCCAGACATGATGCAAGACCCCGTGACCTTCCGCTCCACGCGCCAGATCAGCA ACTTTCCGG

TGGTGGGCGCCGAGCTGTTGCCCGTGCACTCCAAGAGCTTCTACAACGACCAGGCCG TCTACTCCC

AACTCATCCGCCAGTTTACCTCTCTGACCCACGTGTTCAATCGCTTTCCCGAGAACC AGATTTTGGC

GCGCCCGCCAGCCCCCACCATCACCACCGTCAGTGAAAACGTTCCTGCTCTCACAGA TCACGGGAC

GCTACCGCTGCGCAACAGCATCGGAGGAGTCCAGCGAGTGACCATTACTGACGCCAG ACGCCGCA

CCTGCCCCTACGTTTACAAGGCCCTGGGCATAGTCTCGCCGCGCGTCCTATCGAGCC GCACTTTTTG

AGCAAGCATGTCCATCCTTATATCGCCCAGCAATAACACAGGCTGGGGCCTGCGCTT CCCAAGCAA

GATGTTTGGCGGGGCCAAGAAGCGCTCCGACCAACACCCAGTGCGCGTGCGCGGGCA CTACCGCG

CGCCCTGGGGCGCGCACAAACGCGGCCGCACTGGGCGCACCACCGTCGATGACGCCA TCGACGCG

GTGGTGGAGGAGGCGCGCAACTACACGCCCACGCCGCCACCAGTGTCCACAGTGGAC GCGGCCAT

TCAGACCGTGGTGCGCGGAGCCCGGCGCTATGCTAAAATGAAGAGACGGCGGAGGCG CGTAGCAC

GTCGCCACCGCCGCCGACCCGGCACTGCCGCCCAACGCGCGGCGGCGGCCCTGCTTA ACCGCGCA

CGTCGCACCGGCCGACGGGCGGCCATGCGGGCCGCTCGAAGGCTGGCCGCGGGTATT GTCACTGT

GCCCCCCAGGTCCAGGCGACGAGCGGCCGCCGCAGCAGCCGCGGCCATTAGTGCTAT GACTCAGG

GTCGCAGGGGCAACGTGTATTGGGTGCGCGACTCGGTTAGCGGCCTGCGCGTGCCCG TGCGCACC

CGCCCCCCGCGC A ACT AG ATTGC A AG A A A A A ACT ACTT AG ACTCGT ACTGTTGT ATGT ATCC AGCG

GCGGCGGCGCGCAACGAAGCTATGTCCAAGCGCAAAATCAAAGAAGAGATGCTCCAG GTCATCGC

GCCGGAGATCTATGGCCCCCCGAAGAAGGAAGAGCAGGATTACAAGCCCCGAAAGCT AAAGCGG

GTCAAAAAGAAAAAGAAAGATGATGATGATGAACTTGACGACGAGGTGGAACTGCTG CACGCTA

CCGCGCCCAGGCGACGGGTACAGTGGAAAGGTCGACGCGTAAAACGTGTTTTGCGAC CCGGCACC

ACCGTAGTCTTTACGCCCGGTGAGCGCTCCACCCGCACCTACAAGCGCGTGTATGAT GAGGTGTAC

GGCGACGAGGACCTGCTTGAGCAGGCCAACGAGCGCCTCGGGGAGTTTGCCTACGGA AAGCGGCA

TAAGGACATGCTGGCGTTGCCGCTGGACGAGGGCAACCCAACACCTAGCCTAAAGCC CGTAACAC

TGCAGCAGGTGCTGCCCGCGCTTGCACCGTCCGAAGAAAAGCGCGGCCTAAAGCGCG AGTCTGGT

GACTTGGCACCCACCGTGCAGCTGATGGTACCCAAGCGCCAGCGACTGGAAGATGTC TTGGAAAA

AATGACCGTGGAACCTGGGCTGGAGCCCGAGGTCCGCGTGCGGCCAATCAAGCAGGT GGCGCCGG

GACTGGGCGTGCAGACCGTGGACGTTCAGATACCCACTACCAGTAGCACCAGTATTG CCACCGCC

ACAGAGGGCATGGAGACACAAACGTCCCCGGTTGCCTCAGCGGTGGCGGATGCCGCG GTGCAGGC

GGTCGCTGCGGCCGCGTCCAAGACCTCTACGGAGGTGCAAACGGACCCGTGGATGTT TCGCGTTTC

AGCCCCCCGGCGCCCGCGCCGTTCGAGGAAGTACGGCGCCGCCAGCGCGCTACTGCC CGAATATG

CCCTACATCCTTCCATTGCGCCTACCCCCGGCTATCGTGGCTACACCTACCGCCCCA GAAGACGAG

CAACTACCCGACGCCGAACCACCACTGGAACCCGCCGCCGCCGTCGCCGTCGCCAGC CCGTGCTG

GCCCCGATTTCCGTGCGCAGGGTGGCTCGCGAAGGAGGCAGGACCCTGGTGCTGCCA ACAGCGCG

CTACCACCCCAGCATCGTTTAAAAGCCGGTCTTTGTGGTTCTTGCAGATATGGCCCT CACCTGCCGC

CTCCGTTTCCCGGTGCCGGGATTCCGAGGAAGAATGCACCGTAGGAGGGGCATGGCC GGCCACGG

CCTGACGGGCGGCATGCGTCGTGCGCACCACCGGCGGCGGCGCGCGTCGCACCGTCG CATGCGCG

GCGGTATCCTGCCCCTCCTTATTCCACTGATCGCCGCGGCGATTGGCGCCGTGCCCG GAATTGCAT

CCGTGGCCTTGCAGGCGCAGAGACACTGATTAAAAACAAGTTGCATGTGGAAAAATC AAAATAAA AAGTCTGGACTCTCACGCTCGCTTGGTCCTGTAACTATTTTGTAGAATGGAAGACATCAA CTTTGC

GTCTCTGGCCCCGCGACACGGCTCGCGCCCGTTCATGGGAAACTGGCAAGATATCGG CACCAGCA

ATATGAGCGGTGGCGCCTTCAGCTGGGGCTCGCTGTGGAGCGGCATTAAAAATTTCG GTTCCACCG

TTAAGAACTATGGCAGCAAGGCCTGGAACAGCAGCACAGGCCAGATGCTGAGGGATA AGTTGAA

AGAGCAAAATTTCCAACAAAAGGTGGTAGATGGCCTGGCCTCTGGCATTAGCGGGGT GGTGGACC

TGGCCAACCAGGCAGTGCAAAATAAGATTAACAGTAAGCTTGATCCCCGCCCTCCCG TAGAGGAG

CCTCCACCGGCCGTGGAGACAGTGTCTCCAGAGGGGCGTGGCGAAAAGCGTCCGCGC CCCGACAG

GGAAGAAACTCTGGTGACGCAAATAGACGAGCCTCCCTCGTACGAGGAGGCACTAAA GCAAGGCC

TGCCCACCACCCGTCCCATCGCGCCCATGGCTACCGGAGTGCTGGGCCAGCACACAC CCGTAACGC

TGGACCTGCCTCCCCCCGCCGACACCCAGCAGAAACCTGTGCTGCCAGGCCCGACCG CCGTTGTTG

TAACCCGTCCTAGCCGCGCGTCCCTGCGCCGCGCCGCCAGCGGTCCGCGATCGTTGC GGCCCGTAG

CCAGTGGCAACTGGCAAAGCACACTGAACAGCATCGTGGGTCTGGGGGTGCAATCCC TGAAGCGC

CGACGATGCTTCTGATAGCTAACGTGTCGTATGTGTGTCATGTATGCGTCCATGTCG CCGCCAGAG

GAGCTGCTGAGCCGCCGCGCGCCCGCTTTCCAAGATGGCTACCCCTTCGATGATGCC GCAGTGGTC

TTACATGCACATCTCGGGCCAGGACGCCTCGGAGTACCTGAGCCCCGGGCTGGTGCA GTTTGCCCG

CGCCACCGAGACGTACTTCAGCCTGAATAACAAGTTTAGAAACCCCACGGTGGCGCC TACGCACG

ACGTGACCACAGACCGGTCCCAGCGTTTGACGCTGCGGTTCATCCCTGTGGACCGTG AGGATACTG

CGTACTCGTACAAGGCGCGGTTCACCCTAGCTGTGGGTGATAACCGTGTGCTGGACA TGGCTTCCA

CGTACTTTGACATCCGCGGCGTGCTGGACAGGGGCCCTACTTTTAAGCCCTACTCTG GCACTGCCT

ACAACGCCCTGGCTCCCAAGGGTGCCCCAAATCCTTGCGAATGGGATGAAGCTGCTA CTGCTCTTG

AAATAAACCTAGAAGAAGAGGACGATGACAACGAAGACGAAGTAGACGAGCAAGCTG AGCAGCA

A A A A ACTC ACGT ATTTGGGC AGGCGCCTT ATTCTGGT AT AA AT ATT AC A A AGG AGGGT ATTC A A AT

AGGTGTCGAAGGTCAAACACCTAAATATGCCGATAAAACATTTCAACCTGAACCTCA AATAGGAG

AATCTCAGTGGTACGAAACAGAAATTAATCATGCAGCTGGGAGAGTCCTAAAAAAGA CTACCCCA

ATGAAACCATGTTACGGTTCATATGCAAAACCCACAAATGAAAATGGAGGGCAAGGC ATTCTTGT

AAAGCAACAAAATGGAAAGCTAGAAAGTCAAGTGGAAATGCAATTTTTCTCAACTAC TGAGGCAG

CCGCAGGCAATGGTGATAACTTGACTCCTAAAGTGGTATTGTACAGTGAAGATGTAG ATATAGAA

ACCCCAGACACTCATATTTCTTACATGCCCACTATTAAGGAAGGTAACTCACGAGAA CTAATGGGC

C A AC A ATCT ATGCCC A AC AGGCCT A ATT AC ATTGCTTTT AGGG AC A ATTTT ATTGGTCT AATGT ATT

ACAACAGCACGGGTAATATGGGTGTTCTGGCGGGCCAAGCATCGCAGTTGAATGCTG TTGTAGATT

TGCAAGACAGAAACACAGAGCTTTCATACCAGCTTTTGCTTGATTCCATTGGTGATA GAACCAGGT

ACTTTTCTATGTGGAATCAGGCTGTTGACAGCTATGATCCAGATGTTAGAATTATTG AAAATCATG

GAACTGAAGATGAACTTCCAAATTACTGCTTTCCACTGGGAGGTGTGATTAATACAG AGACTCTTA

CCAAGGTAAAACCTAAAACAGGTCAGGAAAATGGATGGGAAAAAGATGCTACAGAAT TTTCAGAT

AAAAATGAAATAAGAGTTGGAAATAATTTTGCCATGGAAATCAATCTAAATGCCAAC CTGTGGAG

A A ATTTCCTGT ACTCC A AC AT AGCGCTGT ATTTGCCCG AC A AGCT A A AGT AC AGTCCTTCC A ACGT

AAAAATTTCTGATAACCCAAACACCTACGACTACATGAACAAGCGAGTGGTGGCTCC CGGGCTAG

TGGACTGCTACATTAACCTTGGAGCACGCTGGTCCCTTGACTATATGGACAACGTCA ACCCATTTA

ACCACCACCGCAATGCTGGCCTGCGCTACCGCTCAATGTTGCTGGGCAATGGTCGCT ATGTGCCCT

TCCACATCCAGGTGCCTCAGAAGTTCTTTGCCATTAAAAACCTCCTTCTCCTGCCGG GCTCATACAC

CTACGAGTGGAACTTCAGGAAGGATGTTAACATGGTTCTGCAGAGCTCCCTAGGAAA TGACCTAA

GGGTTGACGGAGCCAGCATTAAGTTTGATAGCATTTGCCTTTACGCCACCTTCTTCC CCATGGCCC

ACAACACCGCCTCCACGCTTGAGGCCATGCTTAGAAACGACACCAACGACCAGTCCT TTAACGACT

ATCTCTCCGCCGCC A AC ATGCTCT ACCCT AT ACCCGCC A ACGCT ACC A ACGTGCCC AT ATCC ATCC

CCTCCCGCAACTGGGCGGCTTTCCGCGGCTGGGCCTTCACGCGCCTTAAGACTAAGG AAACCCCAT

C ACTGGGCTCGGGCT ACG ACCCTT ATT AC ACCT ACTCTGGCTCT AT ACCCT ACCT AG ATGG A ACCTT

TTACCTCAACCACACCTTTAAGAAGGTGGCCATTACCTTTGACTCTTCTGTCAGCTG GCCTGGCAAT

GACCGCCTGCTTACCCCCAACGAGTTTGAAATTAAGCGCTCAGTTGACGGGGAGGGT TACAACGTT

GCCCAGTGTAACATGACCAAAGACTGGTTCCTGGTACAAATGCTAGCTAACTATAAC ATTGGCTAC

C AGGGCTTCT AT ATCCC AG AG AGCT AC A AGG ACCGC ATGT ACTCCTTCTTT AG A A ACTTCC AGCCC

ATGAGCCGTCAGGTGGTGGATGATACTAAATACAAGGACTACCAACAGGTGGGCATC CTACACCA

ACACAACAACTCTGGATTTGTTGGCTACCTTGCCCCCACCATGCGCGAAGGACAGGC CTACCCTGC

T AACTTCCCCT ATCCGCTT AT AGGC A AG ACCGC AGTTG AC AGC ATT ACCC AG A A A A AGTTTCTTTG

CGATCGCACCCTTTGGCGCATCCCATTCTCCAGTAACTTTATGTCCATGGGCGCACT CACAGACCT

GGGCCAAAACCTTCTCTACGCCAACTCCGCCCACGCGCTAGACATGACTTTTGAGGT GGATCCCAT

GGACGAGCCCACCCTTCTTTATGTTTTGTTTGAAGTCTTTGACGTGGTCCGTGTGCA CCAGCCGCAC

CGCGGCGTCATCGAAACCGTGTACCTGCGCACGCCCTTCTCGGCCGGCAACGCCACA ACATAAAG

AAGCAAGCAACATCAACAACAGCTGCCGCCATGGGCTCCAGTGAGCAGGAACTGAAA GCCATTGT

CAAAGATCTTGGTTGTGGGCCATATTTTTTGGGCACCTATGACAAGCGCTTTCCAGG CTTTGTTTCT CCACACAAGCTCGCCTGCGCCATAGTCAATACGGCCGGTCGCGAGACTGGGGGCGTACAC TGGAT

GGCCTTTGCCTGGAACCCGCACTCAAAAACATGCTACCTCTTTGAGCCCTTTGGCTT TTCTGACCAG

CGACTCAAGCAGGTTTACCAGTTTGAGTACGAGTCACTCCTGCGCCGTAGCGCCATT GCTTCTTCC

CCCGACCGCTGTATAACGCTGGAAAAGTCCACCCAAAGCGTACAGGGGCCCAACTCG GCCGCCTG

TGGACTATTCTGCTGCATGTTTCTCCACGCCTTTGCCAACTGGCCCCAAACTCCCAT GGATCACAAC

CCCACCATGAACCTTATTACCGGGGTACCCAACTCCATGCTCAACAGTCCCCAGGTA CAGCCCACC

CTGCGTCGCAACCAGGAACAGCTCTACAGCTTCCTGGAGCGCCACTCGCCCTACTTC CGCAGCCAC

AGTGCGCAGATTAGGAGCGCCACTTCTTTTTGTCACTTGAAAAACATGTAAAAATAA TGTACTAGA

GACACTTTCAATAAAGGCAAATGCTTTTATTTGTACACTCTCGGGTGATTATTTACC CCCACCCTTG

CCGTCTGCGCCGTTTAAAAATCAAAGGGGTTCTGCCGCGCATCGCTATGCGCCACTG GCAGGGACA

CGTTGCGATACTGGTGTTTAGTGCTCCACTTAAACTCAGGCACAACCATCCGCGGCA GCTCGGTGA

AGTTTTCACTCCACAGGCTGCGCACCATCACCAACGCGTTTAGCAGGTCGGGCGCCG ATATCTTGA

AGTCGCAGTTGGGGCCTCCGCCCTGCGCGCGCGAGTTGCGATACACAGGGTTGCAGC ACTGGAAC

ACTATCAGCGCCGGGTGGTGCACGCTGGCCAGCACGCTCTTGTCGGAGATCAGATCC GCGTCCAG

GTCCTCCGCGTTGCTCAGGGCGAACGGAGTCAACTTTGGTAGCTGCCTTCCCAAAAA GGGCGCGTG

CCCAGGCTTTGAGTTGCACTCGCACCGTAGTGGCATCAAAAGGTGACCGTGCCCGGT CTGGGCGTT

AGGATACAGCGCCTGCATAAAAGCCTTGATCTGCTTAAAAGCCACCTGAGCCTTTGC GCCTTCAGA

GAAGAACATGCCGCAAGACTTGCCGGAAAACTGATTGGCCGGACAGGCCGCGTCGTG CACGCAGC

ACCTTGCGTCGGTGTTGGAGATCTGCACCACATTTCGGCCCCACCGGTTCTTCACGA TCTTGGCCTT

GCTAGACTGCTCCTTCAGCGCGCGCTGCCCGTTTTCGCTCGTCACATCCATTTCAAT CACGTGCTCC

TTATTTATCATAATGCTTCCGTGTAGACACTTAAGCTCGCCTTCGATCTCAGCGCAG CGGTGCAGCC

ACAACGCGCAGCCCGTGGGCTCGTGATGCTTGTAGGTCACCTCTGCAAACGACTGCA GGTACGCCT

GCAGGAATCGCCCCATCATCGTCACAAAGGTCTTGTTGCTGGTGAAGGTCAGCTGCA ACCCGCGGT

GCTCCTCGTTCAGCCAGGTCTTGCATACGGCCGCCAGAGCTTCCACTTGGTCAGGCA GTAGTTTGA

AGTTCGCCTTTAGATCGTTATCCACGTGGTACTTGTCCATCAGCGCGCGCGCAGCCT CCATGCCCTT

CTCCCACGCAGACACGATCGGCACACTCAGCGGGTTCATCACCGTAATTTCACTTTC CGCTTCGCT

GGGCTCTTCCTCTTCCTCTTGCGTCCGCATACCACGCGCCACTGGGTCGTCTTCATT CAGCCGCCGC

ACTGTGCGCTTACCTCCTTTGCCATGCTTGATTAGCACCGGTGGGTTGCTGAAACCC ACCATTTGTA

GCGCC AC ATCTTCTCTTTCTTCCTCGCTGTCC ACG ATT ACT A AT ACG ACTC ACT AT AGGTGTGG AAT

TTCACAGGAGGTACAGCTATGACCATGATTACGGATTCACTGGCCGTCGTTTTACAA CGTCGTGAC

TGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCC AGCTGGCGT

AATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGC GAATAGGT

CGCGCCGCACCGCGTCCGCGCTCGGGGGTGGTTTCGCGCTGCTCCTCTTCCCGACTG GCCATTTCCT

TCTCCTATAGGCAGAAAAAGATCATGGAGTCAGTCGAGAAGAAGGACAGCCTAACCG CCCCCTCT

GAGTTCGCCACCACCGCCTCCACCGATGCCGCCAACGCGCCTACCACCTTCCCCGTC GAGGCACCC

CCGCTTGAGGAGGAGGAAGTGATTATCGAGCAGGACCCAGGTTTTGTAAGCGAAGAC GACGAGGA

CCGCTCAGTACCAACAGAGGATAAAAAGCAAGACCAGGACAACGCAGAGGCAAACGA GGAACAA

GTCGGGCGGGGGGACGAAAGGCATGGCGACTACCTAGATGTGGGAGACGACGTGCTG TTGAAGC

ATCTGCAGCGCCAGTGCGCCATTATCTGCGACGCGTTGCAAGAGCGCAGCGATGTGC CCCTCGCCA

TAGCGGATGTCAGCCTTGCCTACGAACGCCACCTATTCTCACCGCGCGTACCCCCCA AACGCCAAG

AAAACGGCACATGCGAGCCCAACCCGCGCCTCAACTTCTACCCCGTATTTGCCGTGC CAGAGGTGC

TTGCCACCTATCACATCTTTTTCCAAAACTGCAAGATACCCCTATCCTGCCGTGCCA ACCGCAGCC

GAGCGGACAAGCAGCTGGCCTTGCGGCAGGGCGCTGTCATACCTGATATCGCCTCGC TCAACGAA

GTGCCAAAAATCTTTGAGGGTCTTGGACGCGACGAGAAGCGCGCGGCAAACGCTCTG CAACAGGA

AAACAGCGAAAATGAAAGTCACTCTGGAGTGTTGGTGGAACTCGAGGGTGACAACGC GCGCCTAG

CCGTACTAAAACGCAGCATCGAGGTCACCCACTTTGCCTACCCGGCACTTAACCTAC CCCCCAAGG

TCATGAGCACAGTCATGAGTGAGCTGATCGTGCGCCGTGCGCAGCCCCTGGAGAGGG ATGCAAAT

TTGCAAGAACAAACAGAGGAGGGCCTACCCGCAGTTGGCGACGAGCAGCTAGCGCGC TGGCTTCA

AACGCGCGAGCCTGCCGACTTGGAGGAGCGACGCAAACTAATGATGGCCGCAGTGCT CGTTACCG

TGGAGCTTGAGTGCATGCAGCGGTTCTTTGCTGACCCGGAGATGCAGCGCAAGCTAG AGGAAACA

TTGCACTACACCTTTCGACAGGGCTACGTACGCCAGGCCTGCAAGATCTCCAACGTG GAGCTCTGC

AACCTGGTCTCCTACCTTGGAATTTTGCACGAAAACCGCCTTGGGCAAAACGTGCTT CATTCCACG

CTCAAGGGCGAGGCGCGCCGCGACTACGTCCGCGACTGCGTTTACTTATTTCTATGC TACACCTGG

CAGACGGCCATGGGCGTTTGGCAGCAGTGCTTGGAGGAGTGCAACCTCAAGGAGCTG CAGAAACT

GCTAAAGCAAAACTTGAAGGACCTATGGACGGCCTTCAACGAGCGCTCCGTGGCCGC GCACCTGG

CGGACATCATTTTCCCCGAACGCCTGCTTAAAACCCTGCAACAGGGTCTGCCAGACT TCACCAGTC

AAAGCATGTTGCAGAACTTTAGGAACTTTATCCTAGAGCGCTCAGGAATCTTGCCCG CCACCTGCT

GTGCACTTCCTAGCGACTTTGTGCCCATTAAGTACCGCGAATGCCCTCCGCCGCTTT GGGGCCACT

GCTACCTTCTGCAGCTAGCCAACTACCTTGCCTACCACTCTGACATAATGGAAGACG TGAGCGGTG ACGGTCTACTGGAGTGTCACTGTCGCTGCAACCTATGCACCCCGCACCGCTCCCTGGTTT GCAATT

CGCAGCTGCTTAACGAAAGTCAAATTATCGGTACCTTTGAGCTGCAGGGTCCCTCGC CTGACGAAA

AGTCCGCGGCTCCGGGGTTGAAACTCACTCCGGGGCTGTGGACGTCGGCTTACCTTC GCAAATTTG

TACCTGAGGACTACCACGCCCACGAGATTAGGTTCTACGAAGACCAATCCCGCCCGC CTAATGCG

GAGCTTACCGCCTGCGTCATTACCCAGGGCCACATTCTTGGCCAATTGCAAGCCATC AACAAAGCC

CGCCAAGAGTTTCTGCTACGAAAGGGACGGGGGGTTTACTTGGACCCCCAGTCCGGC GAGGAGCT

CAACCCAATCCCCCCGCCGCCGCAGCCCTATCAGCAGCAGCCGCGGGCCCTTGCTTC CCAGGATGG

CACCCAAAAAGAAGCTGCAGCTGCCGCCGCCACCCACGGACGAGGAGGAATACTGGG ACAGTCA

GGCAGAGGAGGTTTTGGACGAGGAGGAGGAGGACATGATGGAAGACTGGGAGAGCCT AGACGAG

GAAGCTTCCGAGGTCGAAGAGGTGTCAGACGAAACACCGTCACCCTCGGTCGCATTC CCCTCGCC

GGCGCCCCAGAAATCGGCAACCGGTTCCAGCATGGCTACAACCTCCGCTCCTCAGGC GCCGCCGG

CACTGCCCGTTCGCCGACCCAACCGTAGATGGGACACCACTGGAACCAGGGCCGGTA AGTCCAAG

CAGCCGCCGCCGTTAGCCCAAGAGCAACAACAGCGCCAAGGCTACCGCTCATGGCGC GGGCACAA

GAACGCCATAGTTGCTTGCTTGCAAGACTGTGGGGGCAACATCTCCTTCGCCCGCCG CTTTCTTCTC

T ACC ATC ACGGCGTGGCCTTCCCCCGT A AC ATCCTGC ATT ACT ACCGTC ATCTCT AC AGCCC AT ACT

GCACCGGCGGCAGCGGCAGCAACAGCAGCGGCCACACAGAAGCAAAGGCGACCGGAT AGCAAGA

CTCTGACAAAGCCCAAGAAATCCACAGCGGCGGCAGCAGCAGGAGGAGGAGCGCTGC GTCTGGC

GCCC A ACG A ACCCGT ATCG ACCCGCG AGCTT AG A A AC AGG ATTTTTCCC ACTCTGT ATGCT AT ATT

TCAACAGAGCAGGGGCCAAGAACAAGAGCTGAAAATAAAAAACAGGTCTCTGCGATC CCTCACCC

GCAGCTGCCTGTATCACAAAAGCGAAGATCAGCTTCGGCGCACGCTGGAAGACGCGG AGGCTCTC

TTC AGT A A AT ACTGCGCGCTG ACTCTT A AGG ACT AGTTTCGCGCCCTTTCTC A A ATTT AAGCGCG A

AAACTACGTCATCTCCAGCGGCCACACCCGGCGCCAGCACCTGTTGTCAGCGCCATT ATGAGCAAG

GAAATTCCCACGCCCTACATGTGGAGTTACCAGCCACAAATGGGACTTGCGGCTGGA GCTGCCCA

AGACTACTCAACCCGAATAAACTACATGAGCGCGGGACCCCACATGATATCCCGGGT CAACGGAA

TACGCGCCCACCGAAACCGAATTCTCCTGGAACAGGCGGCTATTACCACCACACCTC GTAATAACC

TTAATCCCCGTAGTTGGCCCGCTGCCCTGGTGTACCAGGAAAGTCCCGCTCCCACCA CTGTGGTAC

TTCCCAGAGACGCCCAGGCCGAAGTTCAGATGACTAACTCAGGGGCGCAGCTTGCGG GCGGCTTT

CGTCACAGGGTGCGGTCGCCCGGGCAGGGTATAACTCACCTGACAATCAGAGGGCGA GGTATTCA

GCTCAACGACGAGTCGGTGAGCTCCTCGCTTGGTCTCCGTCCGGACGGGACATTTCA GATCGGCGG

CGCCGGCCGCTCTTCATTCACGCCTCGTCAGGCAATCCTAACTCTGCAGACCTCGTC CTCTGAGCC

GCGCTCTGGAGGCATTGGAACTCTGCAATTTATTGAGGAGTTTGTGCCATCGGTCTA CTTTAACCC

CTTCTCGGG ACCTCCCGGCC ACT ATCCGG ATC A ATTT ATTCCT AACTTTG ACGCGGT A A AGG ACTC

GGCGGACGGCTACGACTGAATGTTAAGTGGAGAGGCAGAGCAACTGCGCCTGAAACA CCTGGTCC

ACTGTCGCCGCCACAAGTGCTTTGCCCGCGACTCCGGTGAGTTTTGCTACTTTGAAT TGCCCGAGG

ATCATATCGAGGGCCCGGCGCACGGCGTCCGGCTTACCGCCCAGGGAGAGCTTGCCC GTAGCCTG

ATTCGGGAGTTTACCCAGCGCCCCCTGCTAGTTGAGCGGGACAGGGGACCCTGTGTT CTCACTGTG

ATTTGCAACTGTCCTAACCCTGGATTACATCAAGATCTTTGTTGCCATCTCTGTGCT GAGTATAATA

A AT AC AG A A ATT A A A AT AT ACTGGGGCTCCT ATCGCC ATCCTGT A A ACGCC ACCGTCTTC ACCCGC

CC AAGC A A ACC A AGGCG A ACCTT ACCTGGT ACTTTT A AC ATCTCTCCCTCTGTG ATTT AC A AC AGT

TTCAACCCAGACGGAGTGAGTCTACGAGAGAACCTCTCCGAGCTCAGCTACTCCATC AGAAAAAA

CACCACCCTCCTTACCTGCCGGGAACGTACGAGTGCGTCACCGGCCGCTGCACCACA CCTACCGCC

TGACCGTAAACCAGACTTTTTCCGGACAGACCTCAATAACTCTGTTTACCAGAACAG GAGGTGAGC

TTAGAAAACCCTTAGGGTATTAGGCCAAAGGCGCAGCTACTGTGGGGTTTATGAACA ATTCAAGC

A ACTCT ACGGGCT ATTCTA ATTC AGGTTTCTCT AG A A ATGG ACGG A ATT ATT AC AG AGC AGCGCCT

GCTAGAAAGACGCAGGGCAGCGGCCGAGCAACAGCGCATGAATCAAGAGCTCCAAGA CATGGTT

AACTTGCACCAGTGCAAAAGGGGTATCTTTTGTCTGGTAAAGCAGGCCAAAGTCACC TACGACAG

TAATACCACCGGACACCGCCTTAGCTACAAGTTGCCAACCAAGCGTCAGAAATTGGT GGTCATGGT

GGGAGAAAAGCCCATTACCATAACTCAGCACTCGGTAGAAACCGAAGGCTGCATTCA CTCACCTT

GTCAAGGACCTGAGGATCTCTGCACCCTTATTAAGACCCTGTGCGGTCTCAAAGATC TTATTCCCTT

T AACT A AT A A A A A A A A AT A AT A A AGC ATC ACTT ACTT A A A ATC AGTT AGC A A ATTTCTGTCC AGTT

TATTCAGCAGCACCTCCTTGCCCTCCTCCCAGCTCTGGTATTGCAGCTTCCTCCTGG CTGCAAACTT

TCTCCACAATCTAAATGGAATGTCAGTTTCCTCCTGTTCCTGTCCATCCGCACCCAC TATCTTCATG

TTGTTGCAGATGAAGCGCGCAAGACCGTCTGAAGATACCTTCAACCCCGTGTATCCA TATGACACG

GAAACCGGTCCTCCAACTGTGCCTTTTCTTACTCCTCCCTTTGTATCCCCCAATGGG TTTCAAGAGA

GTCCCCCTGGGGTACTCTCTTTGCGCCTATCCGAACCTCTAGTTACCTCCAATGGCA TGCTTGCGCT

CAAAATGGGCAACGGCCTCTCTCTGGACGAGGCCGGCAACCTTACCTCCCAAAATGT AACCACTGT

GAGCCCACCTCTCAAAAAAACCAAGTCAAACATAAACCTGGAAATATCTGCACCCCT CACAGTTA

CCTCAGAAGCCCTAACTGTGGCTGCCGCCGCACCTCTAATGGTCGCGGGCAACACAC TCACCATGC

AATCACAGGCCCCGCTAACCGTGCACGACTCCAAACTTAGCATTGCCACCCAAGGAC CCCTCACA GTGTCAGAAGGAAAGCTAGCCCTGCAAACATCAGGCCCCCTCACCACCACCGATAGCAGT ACCCT

TACTATCACTGCCTCACCCCCTCTAACTACTGCCACTGGTAGCTTGGGCATTGACTT GAAAGAGCC

C ATTT AT AC AC AAA ATGG A A A ACT AGG ACT A A AGT ACGGGGCTCCTTTGC ATGT A AC AG ACG ACC

TAAACACTTTGACCGTAGCAACTGGTCCAGGTGTGACTATTAATAATACTTCCTTGC AAACTAAAG

TTACTGGAGCCTTGGGTTTTGATTCACAAGGCAATATGCAACTTAATGTAGCAGGAG GACTAAGGA

TTGATTCTCAAAACAGACGCCTTATACTTGATGTTAGTTATCCGTTTGATGCTCAAA ACCAACTAA

ATCT A AG ACT AGG AC AGGGCCCTCTTTTT AT A A ACTC AGCCC AC A ACTTGG AT ATT A ACT AC A AC A

AAGGCCTTTACTTGTTTACAGCTTCAAACAATTCCAAAAAGCTTGAGGTTAACCTAA GCACTGCCA

AGGGGTTGATGTTTGACGCTACAGCCATAGCCATTAATGCAGGAGATGGGCTTGAAT TTGGTTCAC

CTAATGCACCAAACACAAATCCCCTCAAAACAAAAATTGGCCATGGCCTAGAATTTG ATTCAAAC

AAGGCTATGGTTCCTAAACTAGGAACTGGCCTTAGTTTTGACAGCACAGGTGCCATT ACAGTAGGA

AACAAAAATAATGATAAGCTAACTTTGTGGACCACACCAGCTCCATCTCCTAACTGT AGACTAAAT

GCAGAGAAAGATGCTAAACTCACTTTGGTCTTAACAAAATGTGGCAGTCAAATACTT GCTACAGTT

TCAGTTTTGGCTGTTAAAGGCAGTTTGGCTCCAATATCTGGAACAGTTCAAAGTGCT CATCTTATTA

TAAGATTTGACGAAAATGGAGTGCTACTAAACAATTCCTTCCTGGACCCAGAATATT GGAACTTTA

G A A ATGG AG ATCTT ACTG A AGGC AC AGCCT AT AC A A ACGCTGTTGG ATTT ATGCCT A ACCT ATC AG

CTT ATCC A A A ATCTC ACGGT A A A ACTGCC A A A AGT A AC ATTGTC AGTC A AGTTT ACTT A A ACGG AG

AC A A A ACT A A ACCTGT AAC ACT A ACC ATT AC ACT A A ACGGT AC AC AGG A A AC AGG AG AC AC A ACT

CCAAGTGCATACTCTATGTCATTTTCATGGGACTGGTCTGGCCACAACTACATTAAT GAAATATTT

GCCACATCCTCTTACACTTTTTCATACATTGCCCAAGAATAAAGAATCGTTTGTGTT ATGTTTCAAC

GTGTTTATTTTTCAATTGCAGAAAATTTCGAATCATTTTTCATTCAGTAGTATAGCC CCACCACCAC

AT AGCTT AT AC AG ATC ACCGT ACCTT AATC A A ACTC AC AG A ACCCT AGT ATTC A ACCTGCC ACCTC

CCTCCCAACACACAGAGTACACAGTCCTTTCTCCCCGGCTGGCCTTAAAAAGCATCA TATCATGGG

T AAC AG AC AT ATTCTT AGGTGTT AT ATTCC AC ACGGTTTCCTGTCG AGCC A A ACGCTC ATC AGTG A

TATTAATAAACTCCCCGGGCAGCTCACTTAAGTTCATGTCGCTGTCCAGCTGCTGAG CCACAGGCT

GCTGTCCAACTTGCGGTTGCTTAACGGGCGGCGAAGGAGAAGTCCACGCCTACATGG GGGTAGAG

TCATAATCGTGCATCAGGATAGGGCGGTGGTGCTGCAGCAGCGCGCGAATAAACTGC TGCCGCCG

CCGCTCCGTCCTGCAGGAATACAACATGGCAGTGGTCTCCTCAGCGATGATTCGCAC CGCCCGCAG

CATAAGGCGCCTTGTCCTCCGGGCACAGCAGCGCACCCTGATCTCACTTAAATCAGC ACAGTAACT

GCAGCACAGCACCACAATATTGTTCAAAATCCCACAGTGCAAGGCGCTGTATCCAAA GCTCATGG

CGGGGACCACAGAACCCACGTGGCCATCATACCACAAGCGCAGGTAGATTAAGTGGC GACCCCTC

ATAAACACGCTGGACATAAACATTACCTCTTTTGGCATGTTGTAATTCACCACCTCC CGGTACCAT

ATAAACCTCTGATTAAACATGGCGCCATCCACCACCATCCTAAACCAGCTGGCCAAA ACCTGCCCG

CCGGCTATACACTGCAGGGAACCGGGACTGGAACAATGACAGTGGAGAGCCCAGGAC TCGTAACC

ATGG ATCATCATGCTCGTCATGAT ATC AATGTTGGCACAACACAGGCACACGTGCATACACTTCCT

C AGG ATT AC A AGCTCCTCCCGCGTT AG A ACC AT ATCCC AGGG A AC A ACCC ATTCCTG A ATC AGCGT

AAATCCCACACTGCAGGGAAGACCTCGCACGTAACTCACGTTGTGCATTGTCAAAGT GTTACATTC

GGGCAGCAGCGGATGATCCTCCAGTATGGTAGCGCGGGTTTCTGTCTCAAAAGGAGG TAGACGAT

CCCTACTGTACGGAGTGCGCCGAGACAACCGAGATCGTGTTGGTCGTAGTGTCATGC CAAATGGA

ACGCCGGACGTAGTCATATTTCCTGAAGCAAAACCAGGTGCGGGCGTGACAAACAGA TCTGCGTC

TCCGGTCTCGCCGCTT AG ATCGCTCTGTGT AGT AGTTGT AGT AT ATCC ACTCTCTC A A AGC ATCC AG

GCGCCCCCTGGCTTCGGGTTCTATGTAAACTCCTTCATGCGCCGCTGCCCTGATAAC ATCCACCACC

GCAGAATAAGCCACACCCAGCCAACCTACACATTCGTTCTGCGAGTCACACACGGGA GGAGCGGG

AAGAGCTGGAAGAACCATGTTTTTTTTTTT ATTCC AAAAGATTATCCAAAACCTCAAAATGAAG AT

CTATTAAGTGAACGCGCTCCCCTCCGGTGGCGTGGTCAAACTCTACAGCCAAAGAAC AGATAATG

GCATTTGTAAGATGTTGCACAATGGCTTCCAAAAGGCAAACGGCCCTCACGTCCAAG TGGACGTA

AAGGCTAAACCCTTCAGGGTGAATCTCCTCTATAAACATTCCAGCACCTTCAACCAT GCCCAAATA

ATTCTC ATCTCGCC ACCTTCTC A AT AT ATCTCT A AGC A A ATCCCG A AT ATT A AGTCCGGCC ATTGT A

AAAATCTGCTCCAGAGCGCCCTCCACCTTCAGCCTCAAGCAGCGAATCATGATTGCA AAAATTCAG

GTTCCTC AC AG ACCTGT AT A AG ATTC AAA AGCGG A AC ATT AAC A A A A AT ACCGCG ATCCCGT AGG

TCCCTTCGCAGGGCCAGCTGAACATAATCGTGCAGGTCTGCACGGACCAGCGCGGCC ACTTCCCCG

CCAGGAACCATGACAAAAGAACCCACACTGATTATGACACGCATACTCGGAGCTATG CTAACCAG

CGTAGCCCCGATGTAAGCTTGTTGCATGGGCGGCGATATAAAATGCAAGGTGCTGCT CAAAAAAT

CAGGCAAAGCCTCGCGCAAAAAAGAAAGCACATCGTAGTCATGCTCATGCAGATAAA GGCAGGTA

AGCTCCGGAACCACCACAGAAAAAGACACCATTTTTCTCTCAAACATGTCTGCGGGT TTCTGCATA

A AC AC A A A AT A A A AT A AC A A A A A A AC ATTT A A AC ATT AG A AGCCTGTCTT AC A AC AGG A A A A AC A

ACCCTTATAAGCATAAGACGGACTACGGCCATGCCGGCGTGACCGTAAAAAAACTGG TCACCGTG

ATTAAAAAGCACCACCGACAGCTCCTCGGTCATGTCCGGAGTCATAATGTAAGACTC GGTAAACA

CATCAGGTTGATTCACATCGGTCAGTGCTAAAAAGCGACCGAAATAGCCCGGGGGAA TACATACC CGCAGGCGTAGAGACAACATTACAGCCCCCATAGGAGGTATAACAAAATTAATAGGAGAG AAAA

ACACATAAACACCTGAAAAACCCTCCTGCCTAGGCAAAATAGCACCCTCCCGCTCCA GAACAACA

T AC AGCGCTTCC AC AGCGGC AGCC AT A AC AGTC AGCCTT ACC AGT A A A A A AG A A A ACCT ATT AAA

AAAACACCACTCGACACGGCACCAGCTCAATCAGTCACAGTGTAAAAAAGGGCCAAG TGCAGAGC

GAGTATATATAGGACTAAAAAATGACGTAACGGTTAAAGTCCACAAAAAACACCCAG AAAACCGC

ACGCGAACCTACGCCCAGAAACGAAAGCCAAAAAACCCACAACTTCCTCAAATCGTC ACTTCCGT

TTTCCC ACGTT ACGTC ACTTCCC ATTTT A AG A A A ACT AC A ATTCCC A AC AC AT AC A AGTT ACTCCGC

CCTAAAACCTACGTCACCCGCCCCGTTCCCACGCCCCGCGCCACGTCACAAACTCCA CCCCCTCAT

TATCATATTGGCTTCAATCCAAAATAAGGTATATTATTGATGATGTTAATTAATTTA AATCCGCATG

CGATATCGAGCTCTCCCGGGAATTCGGATCTGCGACGCGAGGCTGGATGGCCTTCCC CATTATGAT

TCTTCTCGCGTTT AAGGGC ACC A AT A ACTGCCTT A A A A A A ATT ACGCCCCGCCCTGCC ACTC ATCG

CAGTACTGTTGTAATTCATTAAGCATTCTGCCGACATGGAAGCCATCACAAACGGCA TGATGAACC

TGAATCGCCAGCGGCATCAGCACCTTGTCGCCTTGCGTATAATATTTGCCCATGGTG AAAACGGGG

GCGAAGAAGTTGTCCATATTGGCCACGTTTAAATCAAAACTGGTGAAACTCACCCAG GGATTGGCT

G AG ACG A A A A AC AT ATTCTC A AT A A ACCCTTT AGGG A A AT AGGCC AGGTTTTC ACCGT A AC ACGC

CACATCTTGCGAATATATGTGTAGAAACTGCCGGAAATCGTCGTGGTATTCACTCCA GAGCGATGA

AAACGTTTCAGTTTGCTCATGGAAAACGGTGTAACAAGGGTGAACACTATCCCATAT CACCAGCTC

ACCGTCTTTCATTGCCATACGGAATTCCGGATGAGCATTCATCAGGCGGGCAAGAAT GTGAATAAA

GGCCGG AT A A A ACTTGTGCTT ATTTTTCTTT ACGGTCTTT A A A A AGGCCGT A AT ATCC AGCTG A AC

GGTCTGGTTATAGGTACATTGAGCAACTGACTGAAATGCCTCAAAATGTTCTTTACG ATGCCATTG

GGATATATCAACGGTGGTATATCCAGTGATTTTTTTCTCCATTTTAGCTTCCTTAGC TCCTGAAAAT

CTCGATAACTCAAAAAATACGCCCGGTAGTGATCTTATTTCATTATGGTGAAAGTTG GAACCTCTT

ACGTGCCGATCAACGTCTCATTTTCGCCAAAAGTTGGCCCAGGGCTTCCCGGTATCA ACAGGGACA

CC AGG ATTT ATTT ATTCTGCG A AGTG ATCTTCCGTC AC AGGT ATTT ATTCGCG AT AAGCTC ATGG AG

CGGCGTAACCGTCGCACAGGAAGGACAGAGAAAGCGCGGATCTGGGAAGTGACGGAC AGAACGG

TCAGGACCTGGATTGGGGAGGCGGTTGCCGCCGCTGCTGCTGACGGTGTGACGTTCT CTGTTCCGG

TCACACCACATACGTTCCGCCATTCCTATGCGATGCACATGCTGTATGCCGGTATAC CGCTGAAAG

TTCTGCAAAGCCTGATGGGACATAAGTCCATCAGTTCAACGGAAGTCTACACGAAGG TTTTTGCGC

TGGATGTGGCTGCCCGGCACCGGGTGCAGTTTGCGATGCCGGAGTCTGATGCGGTTG CGATGCTGA

AACAATTATCCTGAGAATAAATGCCTTGGCCTTTATATGGAAATGTGGAACTGAGTG GATATGCTG

TTTTTGTCTGTTAAACAGAGAAGCTGGCTGTTATCCACTGAGAAGCGAACGAAACAG TCGGGAAA

ATCTCCC ATT ATCGT AG AG ATCCGC ATT ATT A ATCTC AGG AGCCTGTGT AGCGTTT AT AGG A AGT A

GTGTTCTGTCATGATGCCTGCAAGCGGTAACGAAAACGATTTGAATATGCCTTCAGG AACAATAGA

AATCTTCGTGCGGTGTTACGTTGAAGTGGAGCGGATTATGTCAGCAATGGACAGAAC AACCTAAT

GAACACAGAACCATGATGTGGTCTGTCCTTTTACAGCCAGTAGTGCTCGCCGCAGTC GAGCGACAG

GGCGAAGCCCTCGAGTGAGCGAGGAAGCACCAGGGAACAGCACTTATATATTCTGCT TACACACG

ATGCCTG A A A A A ACTTCCCTTGGGGTT ATCC ACTT ATCC ACGGGG AT ATTTTT AT AATT ATTTTTTT

T AT AGTTTTT AG ATCTTCTTTTTT AG AGCGCCTTGTAGGCCTTT ATCC ATGCTGGTTCT AG AG A AGG

TGTTGTGACAAATTGCCCTTTCAGTGTGACAAATCACCCTCAAATGACAGTCCTGTC TGTGACAAA

TTGCCCTTAACCCTGTGACAAATTGCCCTCAGAAGAAGCTGTTTTTTCACAAAGTTA TCCCTGCTTA

TTGACTCTTTTTTATTTAGTGTGACAATCTAAAAACTTGTCACACTTCACATGGATC TGTCATGGCG

GAAACAGCGGTTATCAATCACAAGAAACGTAAAAATAGCCCGCGAATCGTCCAGTCA AACGACCT

CACTGAGGCGGCATATAGTCTCTCCCGGGATCAAAAACGTATGCTGTATCTGTTCGT TGACCAGAT

CAGAAAATCTGATGGCACCCTACAGGAACATGACGGTATCTGCGAGATCCATGTTGC TAAATATG

CTGAAATATTCGGATTGACCTCTGCGGAAGCCAGTAAGGATATACGGCAGGCATTGA AGAGTTTC

GCGGGGAAGGAAGTGGTTTTTTATCGCCCTGAAGAGGATGCCGGCGATGAAAAAGGC TATGAATC

TTTTCCTTGGTTTATCAAACGTGCGCACAGTCCATCCAGAGGGCTTTACAGTGTACA TATCAACCC

AT ATCTC ATTCCCTTCTTTATCGGGTT AC AG A ACCGGTTT ACGC AGTTTCGGCTT AGTG A A AC A A A A

G AAATCACCAATCCGT ATGCCATGCGTTT AT ACGAATCCCTGTGTCAGT ATCGT AAGCCGGATGGC

TCAGGCATCGTCTCTCTGAAAATCGACTGGATCATAGAGCGTTACCAGCTGCCTCAA AGTTACCAG

CGTATGCCTGACTTCCGCCGCCGCTTCCTGCAGGTCTGTGTTAATGAGATCAACAGC AGAACTCCA

ATGCGCCTCTCAT ACATTGAGAAAAAG AAAGGCCGCCAG ACG ACTCAT ATCGT ATTTTCCTTCCGC

GATATCACTTCCATGACGACAGGATAGTCTGAGGGTTATCTGTCACAGATTTGAGGG TGGTTCGTC

ACATTTGTTCTGACCTACTGAGGGTAATTTGTCACAGTTTTGCTGTTTCCTTCAGCC TGCATGGATT

TTCTCATACTTTTTGAACTGTAATTTTTAAGGAAGCCAAATTTGAGGGCAGTTTGTC ACAGTTGATT

TCCTTCTCTTTCCCTTCGTCATGTGACCTGATATCGGGGGTTAGTTCGTCATCATTG ATGAGGGTTG

ATTATCACAGTTTATTACTCTGAATTGGCTATCCGCGTGTGTACCTCTACCTGGAGT TTTTCCCACG

GTGGATATTTCTTCTTGCGCTGAGCGTAAGAGCTATCTGACAGAACAGTTCTTCTTT GCTTCCTCGC

CAGTTCGCTCGCTATGCTCGGTTACACGGCTGCGGCGAGCGCTAGTGATAATAAGTG ACTGAGGTA TGTGCTCTTCTTATCTCCTTTTGTAGTGTTGCTCTTATTTTAAACAACTTTGCGGTTTTT TGATGACT

TTGCGATTTTGTTGTTGCTTTGCAGTAAATTGCAAGATTTAATAAAAAAACGCAAAG CAATGATTA

AAGGATGTTCAGAATGAAACTCATGGAAACACTTAACCAGTGCATAAACGCTGGTCA TGAAATGA

CGAAGGCTATCGCCATTGCACAGTTTAATGATGACAGCCCGGAAGCGAGGAAAATAA CCCGGCGC

TGGAGAATAGGTGAAGCAGCGGATTTAGTTGGGGTTTCTTCTCAGGCTATCAGAGAT GCCGAGAA

AGCAGGGCGACTACCGCACCCGGATATGGAAATTCGAGGACGGGTTGAGCAACGTGT TGGTTATA

CAATTGAACAAATTAATCATATGCGTGATGTGTTTGGTACGCGATTGCGACGTGCTG AAGACGTAT

TTCCACCGGTGATCGGGGTTGCTGCCCATAAAGGTGGCGTTTACAAAACCTCAGTTT CTGTTCATCT

TGCTCAGGATCTGGCTCTGAAGGGGCTACGTGTTTTGCTCGTGGAAGGTAACGACCC CCAGGGAAC

AGCCTCAATGTATCACGGATGGGTACCAGATCTTCATATTCATGCAGAAGACACTCT CCTGCCTTT

CTATCTTGGGGAAAAGGACGATGTCACTTATGCAATAAAGCCCACTTGCTGGCCGGG GCTTGACAT

TATTCCTTCCTGTCTGGCTCTGCACCGTATTGAAACTGAGTTAATGGGCAAATTTGA TGAAGGTAA

ACTGCCCACCGATCCACACCTGATGCTCCGACTGGCCATTGAAACTGTTGCTCATGA CTATGATGT

CATAGTTATTGACAGCGCGCCTAACCTGGGTATCGGCACGATTAATGTCGTATGTGC TGCTGATGT

GCTGATTGTTCCCACGCCTGCTGAGTTGTTTGACTACACCTCCGCACTGCAGTTTTT CGATATGCTT

CGTGATCTGCTCAAGAACGTTGATCTTAAAGGGTTCGAGCCTGATGTACGTATTTTG CTTACCAAA

TACAGCAATAGTAATGGCTCTCAGTCCCCGTGGATGGAGGAGCAAATTCGGGATGCC TGGGGAAG

CATGGTTCTAAAAAATGTTGTACGTGAAACGGATGAAGTTGGTAAAGGTCAGATCCG GATGAGAA

CTGTTTTTGAACAGGCCATTGATCAACGCTCTTCAACTGGTGCCTGGAGAAATGCTC TTTCTATTTG

GGAACCTGTCTGCAATGAAATTTTCGATCGTCTGATTAAACCACGCTGGGAGATTAG ATAATGAAG

CGTGCGCCTGTT ATTCC A A A AC AT ACGCTC A AT ACTC A ACCGGTTG A AG AT ACTTCGTT ATCG AC A

CCAGCTGCCCCGATGGTGGATTCGTTAATTGCGCGCGTAGGAGTAATGGCTCGCGGT AATGCCATT

ACTTTGCCTGTATGTGGTCGGGATGTGAAGTTTACTCTTGAAGTGCTCCGGGGTGAT AGTGTTGAG

AAGACCTCTCGGGTATGGTCAGGTAATGAACGTGACCAGGAGCTGCTTACTGAGGAC GCACTGGA

TGATCTCATCCCTTCTTTTCTACTGACTGGTCAACAGACACCGGCGTTCGGTCGAAG AGTATCTGGT

GTCATAGAAATTGCCGATGGGAGTCGCCGTCGTAAAGCTGCTGCACTTACCGAAAGT GATTATCGT

GTTCTGGTTGGCGAGCTGGATGATGAGCAGATGGCTGCATTATCCAGATTGGGTAAC GATTATCGC

CCAACAAGTGCTTATGAACGTGGTCAGCGTTATGCAAGCCGATTGCAGAATGAATTT GCTGGAAAT

ATTTCTGCGCTGGCTGATGCGGAAAATATTTCACGTAAGATTATTACCCGCTGTATC AACACCGCC

AAATTGCCTAAATCAGTTGTTGCTCTTTTTTCTCACCCCGGTGAACTATCTGCCCGG TCAGGTGATG

C ACTTC A A A A AGCCTTT AC AG AT A A AG AGG A ATT ACTT A AGC AGC AGGC ATCT A ACCTTC ATG AG

CAGAAAAAAGCTGGGGTGATATTTGAAGCTGAAGAAGTTATCACTCTTTTAACTTCT GTGCTTAAA

ACGTCATCTGCATCAAGAACTAGTTTAAGCTCACGACATCAGTTTGCTCCTGGAGCG ACAGTATTG

TATAAGGGCGATAAAATGGTGCTTAACCTGGACAGGTCTCGTGTTCCAACTGAGTGT ATAGAGAA

AATTGAGGCCATTCTTAAGGAACTTGAAAAGCCAGCACCCTGATGCGACCACGTTTT AGTCTACGT

TTATCTGTCTTTACTTAATGTCCTTTGTTACAGGCCAGAAAGCATAACTGGCCTGAA TATTCTCTCT

GGGCCCACTGTTCCACTTGTATCGTCGGTCTGATAATCAGACTGGGACCACGGTCCC ACTCGTATC

GTCGGTCTGATTATTAGTCTGGGACCACGGTCCCACTCGTATCGTCGGTCTGATTAT TAGTCTGGGA

CCACGGTCCCACTCGTATCGTCGGTCTGATAATCAGACTGGGACCACGGTCCCACTC GTATCGTCG

GTCTGATTATTAGTCTGGGACCATGGTCCCACTCGTATCGTCGGTCTGATTATTAGT CTGGGACCAC

GGTCCCACTCGTATCGTCGGTCTGATTATTAGTCTGGAACCACGGTCCCACTCGTAT CGTCGGTCTG

ATT ATT AGTCTGGG ACC ACGGTCCC ACTCGT ATCGTCGGTCTG ATT ATT AGTCTGGG ACC ACG ATC

CCACTCGTGTTGTCGGTCTGATTATCGGTCTGGGACCACGGTCCCACTTGTATTGTC GATCAGACTA

TCAGCGTGAGACTACGATTCCATCAATGCCTGTCAAGGGCAAGTATTGACATGTCGT CGTAACCTG

TAGAACGGAGTAACCTCGGTGTGCGGTTGTATGCCTGCTGTGGATTGCTGCTGTGTC CTGCTTATCC

ACAACATTTTGCGCACGGTTATGTGGACAAAATACCTGGTTACCCAGGCCGTGCCGG CACGTTAAC

CGGGCACATTTCCCCGAAAAGTGCCACCTGACGTCTAAGAAACCATTATTATCATGA CATTAACCT

ATAAAAATAGGCGTATCACGAGGCCCTTTCGTCTTCAAGAATTGGATCCGAATTCCC GGGAGAGCT

CG AT ATCGC ATGCGG ATTT A A ATT A ATT A A

* C1C (SEQ ID NO: 84)

CATCATCAATAATATACCTTATTTTGGATTGAAGCCAATATGATAATGAGGGGGTGGAGT TTGTGA

CGTGGCGCGGGGCGTGGGAACGGGGCGGGTGACGTAGTAGTGTGGCGGAAGTGTGAT GTTGCAAG

TGTGGCGGAACACATGTAAGCGACGGATGTGGCAAAAGTGACGTTTTTGGTGTGCGC CGGTGTAC

ACAGGAAGTGACAATTTTCGCGCGGTTTTAGGCGGATGTTGTAGTAAATTTGGGCGT AACCGAGTA

AGATTTGGCCATTTTCGCGGGAAAACTGAATAAGAGGAAGTGAAATCTGAATAATTT TGTGTTACT

CATAGCGCGTAATATTTGTCTAGGGCCGCGGGGACTTTGACCGTTTACGTGGAGACT CGCCCAGGT _{GTTTTTCTCAGGTGTTTTCCGCGTTCCGGGTCAAAGTTGGCGTTTTATTATTATA GTCAGTCGAAGC}

TTGGATCCGGTACCTCTAGAATTCTCGAGCGGCCGCTAGCGACATCGGATCTCCCGA TCCCCTATG

GTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGTATCTGCTCCC TGCTTGTGTG

TTGGAGGTCGCTGAGTAGTGCGCGAGCAAAATTTAAGCTACAACAAGGCAAGGCTTG ACCGACAA

TTGCATGAAGAATCTGCTTAGGGTTAGGCGTTTTGCGCTGCTTCGCGATGTACGGGC CAGATATAC

GCGTTG AC ATTG ATT ATTG ACT AGTT ATT AAT AGT A ATC A ATT ACGGGGTC ATT AGTTC AT AGCCC

ATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCC CAACGACCC

CCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTT CCATTGACG

TCAATGGGTGGACTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCA TATGCCAAG

TACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTA CATGACCTT

ATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGT GATGCGGTTT

TGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTC CACCCCATT

GACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGT AACAACTCC

GCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGA GCTCTCTG

GCT A ACT AG AG A ACCC ACTGCTT ACTGGCTT ATCGA A ATG AG ACCC A AGCTGGCT AGTT A AGCT AT

CAACAAGTTTGTACAAAAAAGCAGGCTTTAAAGGAACCAATTCAGTCGACTGGATCC GGTACCAC

CATGTTCCTGAACTGCTGCCCAGGTTGCTGTATGGAGCCTGAATTCACCATGGTGAG CAAGGGCGA

GGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGG CCACAAGT

TCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGT TCATCTGC

ACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTGGGGC GTGCAGTGC

TTCGCCCGCTACCCCGACCACATGAAGCAGCACGACTTCTTCAAGTCCGCCATGCCC GAAGGCTAC

GTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAG GTGAAGTT

CGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGA CGGCAAC

ATCCTGGGGCACAAGCTGGAGTACAACGCCATCAGCGACAACGTCTATATCACCGCC GACAAGCA

GAAGAACGGCATCAAGGCCAACTTCAAGATCCGCCACAACATCGAGGACGGCAGCGT GCAGCTCG

CCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGCCCGACA ACCACTAC

CTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTC CTGCTGGA

GTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAGGTCGACTA TCCGTACGA

CGT ACC AG ACT ACGC AT A ACCGCGGCCGC ACTCG AG AT ATCT AG ACCC AGCTTTCTTGT AC A A AGT

GGTTGATCTAGAGGGCCCGCGGTTCGAAGGTAAGCCTATCCCTAACCCTCTCCTCGG TCTCGATTC

TACGCGTACCGGTTAGTAATGAGTTTAAACGGGGGAGGCTAACTGAAACACGGAAGG AGACAATA

CCGGAAGGAACCCGCGCTATGACGGCAATAAAAAGACAGAATAAAACGCACGGGTGT TGGGTCG

TTTGTTCATAAACGCGGGGTTCGGTCCCAGGGCTGGCACTCTGTCGATACCCCACCG AGACCCCAT

TGGGGCCAATACGCCCGCGTTTCTTCCTTTTCCCCACCCCACCCCCCAAGTTCGGGT GAAGGCCCA

GGGCTCGCAGCCAACGTCGGGGCGGCAGGCCCTGCCATAGCAGATCCGATTCGACAG ATCACTGA

AATGTGTGGGCGTGGCTTAAGGGTGGGAAAGAATATATAAGGTGGGGGTCTTATGTA GTTTTGTAT

CTGTTTTGCAGCAGCCGCCGCCGCCATGAGCACCAACTCGTTTGATGGAAGCATTGT GAGCTCATA

TTTGACAACGCGCATGCCCCCATGGGCCGGGGTGCGTCAGAATGTGATGGGCTCCAG CATTGATG

GTCGCCCCGTCCTGCCCGCAAACTCTACTACCTTGACCTACGAGACCGTGTCTGGAA CGCCGTTGG

AGACTGCAGCCTCCGCCGCCGCTTCAGCCGCTGCAGCCACCGCCCGCGGGATTGTGA CTGACTTTG

CTTTCCTGAGCCCGCTTGCAAGCAGTGCAGCTTCCCGTTCATCCGCCCGCGATGACA AGTTGACGG

CTCTTTTGGCACAATTGGATTCTTTGACCCGGGAACTTAATGTCGTTTCTCAGCAGC TGTTGGATCT

GCGCCAGCAGGTTTCTGCCCTGAAGGCTTCCTCCCCTCCCAATGCGGTTTAAAACAT AAATAAAAA

ACCAGACTCTGTTTGGATTTGGATCAAGCAAGTGTCTTGCTGTCTTTATTTAGGGGT TTTGCGCGCG

CGGTAGGCCCGGGACCAGCGGTCTCGGTCGTTGAGGGTCCTGTGTATTTTTTCCAGG ACGTGGTAA

AGGTGACTCTGGATGTTCAGATACATGGGCATAAGCCCGTCTCTGGGGTGGAGGTAG CACCACTG

CAGAGCTTCATGCTGCGGGGTGGTGTTGTAGATGATCCAGTCGTAGCAGGAGCGCTG GGCGTGGT

GCCTAAAAATGTCTTTCAGTAGCAAGCTGATTGCCAGGGGCAGGCCCTTGGTGTAAG TGTTTACAA

AGCGGTTAAGCTGGGATGGGTGCATACGTGGGGATATGAGATGCATCTTGGACTGTA TTTTTAGGT

TGGCTATGTTCCCAGCCATATCCCTCCGGGGATTCATGTTGTGCAGAACCACCAGCA CAGTGTATC

CGGTGCACTTGGGAAATTTGTCATGTAGCTTAGAAGGAAATGCGTGGAAGAACTTGG AGACGCCC

TTGTGACCTCCAAGATTTTCCATGCATTCGTCCATAATGATGGCAATGGGCCCACGG GCGGCGGCC

TGGGCGAAGATATTTCTGGGATCACTAACGTCATAGTTGTGTTCCAGGATGAGATCG TCATAGGCC

_{ATTTTTACAAAGCGCGGGCGGAGGGTGCCAGACTGCGGTATAATGGTTCCATCCG GCCCAGGGGC}

GTAGTTACCCTCACAGATTTGCATTTCCCACGCTTTGAGTTCAGATGGGGGGATCAT GTCTACCTGC

GGGGCGATGAAGAAAACGGTTTCCGGGGTAGGGGAGATCAGCTGGGAAGAAAGCAGG TTCCTGA

GCAGCTGCGACTTACCGCAGCCGGTGGGCCCGTAAATCACACCTATTACCGGCTGCA ACTGGTAGT

TAAGAGAGCTGCAGCTGCCGTCATCCCTGAGCAGGGGGGCCACTTCGTTAAGCATGT CCCTGACTC

GCATGTTTTCCCTGACCAAATCCGCCAGAAGGCGCTCGCCGCCCAGCGATAGCAGTT CTTGCAAGG AAGCAAAGTTTTTCAACGGTTTGAGACCGTCCGCCGTAGGCATGCTTTTGAGCGTTTGAC CAAGCA

GTTCCAGGCGGTCCCACAGCTCGGTCACCTGCTCTACGGCATCTCGATCCAGCATAT CTCCTCGTTT

CGCGGGTTGGGGCGGCTTTCGCTGTACGGCAGTAGTCGGTGCTCGTCCAGACGGGCC AGGGTCAT

GTCTTTCCACGGGCGCAGGGTCCTCGTCAGCGTAGTCTGGGTCACGGTGAAGGGGTG CGCTCCGGG

CTGCGCGCTGGCCAGGGTGCGCTTGAGGCTGGTCCTGCTGGTGCTGAAGCGCTGCCG GTCTTCGCC

CTGCGCGTCGGCCAGGTAGCATTTGACCATGGTGTCATAGTCCAGCCCCTCCGCGGC GTGGCCCTT

GGCGCGCAGCTTGCCCTTGGAGGAGGCGCCGCACGAGGGGCAGTGCAGACTTTTGAG GGCGTAGA

GCTTGGGCGCGAGAAATACCGATTCCGGGGAGTAGGCATCCGCGCCGCAGGCCCCGC AGACGGTC

TCGCATTCCACGAGCCAGGTGAGCTCTGGCCGTTCGGGGTCAAAAACCAGGTTTCCC CCATGCTTT

TTGATGCGTTTCTTACCTCTGGTTTCCATGAGCCGGTGTCCACGCTCGGTGACGAAA AGGCTGTCC

GTGTCCCCGTATACAGACTTGAGAGGCCTGTCCTCGAGCGGTGTTCCGCGGTCCTCC TCGTATAGA

AACTCGGACCACTCTGAGACAAAGGCTCGCGTCCAGGCCAGCACGAAGGAGGCTAAG TGGGAGG

GGTAGCGGTCGTTGTCCACTAGGGGGTCCACTCGCTCCAGGGTGTGAAGACACATGT CGCCCTCTT

CGGCATCAAGGAAGGTGATTGGTTTGTAGGTGTAGGCCACGTGACCGGGTGTTCCTG AAGGGGGG

CTATAAAAGGGGGTGGGGGCGCGTTCGTCCTCACTCTCTTCCGCATCGCTGTCTGCG AGGGCCAGC

TGTTGGGGTGAGTACTCCCTCTGAAAAGCGGGCATGACTTCTGCGCTAAGATTGTCA GTTTCCAAA

AACGAGGAGGATTTGATATTCACCTGGCCCGCGGTGATGCCTTTGAGGGTGGCCGCA TCCATCTGG

TCAGAAAAGACAATCTTTTTGTTGTCAAGCTTGGTGGCAAACGACCCGTAGAGGGCG TTGGACAG

CAACTTGGCGATGGAGCGCAGGGTTTGGTTTTTGTCGCGATCGGCGCGCTCCTTGGC CGCGATGTT

TAGCTGCACGTATTCGCGCGCAACGCACCGCCATTCGGGAAAGACGGTGGTGCGCTC GTCGGGCA

CCAGGTGCACGCGCCAACCGCGGTTGTGCAGGGTGACAAGGTCAACGCTGGTGGCTA CCTCTCCG

CGTAGGCGCTCGTTGGTCCAGCAGAGGCGGCCGCCCTTGCGCGAGCAGAATGGCGGT AGGGGGTC

TAGCTGCGTCTCGTCCGGGGGGTCTGCGTCCACGGTAAAGACCCCGGGCAGCAGGCG CGCGTCGA

AGTAGTCTATCTTGCATCCTTGCAAGTCTAGCGCCTGCTGCCATGCGCGGGCGGCAA GCGCGCGCT

CGTATGGGTTGAGTGGGGGACCCCATGGCATGGGGTGGGTGAGCGCGGAGGCGTACA TGCCGCAA

ATGTCGTAAACGTAGAGGGGCTCTCTGAGTATTCCAAGATATGTAGGGTAGCATCTT CCACCGCGG

ATGCTGGCGCGCACGTAATCGTATAGTTCGTGCGAGGGAGCGAGGAGGTCGGGACCG AGGTTGCT

ACGGGCGGGCTGCTCTGCTCGGAAGACTATCTGCCTGAAGATGGCATGTGAGTTGGA TGATATGGT

TGGACGCTGGAAGACGTTGAAGCTGGCGTCTGTGAGACCTACCGCGTCACGCACGAA GGAGGCGT

AGGAGTCGCGCAGCTTGTTGACCAGCTCGGCGGTGACCTGCACGTCTAGGGCGCAGT AGTCCAGG

GTTTCCTTGATGATGTCATACTTATCCTGTCCCTTTTTTTTCCACAGCTCGCGGTTG AGGACAAACT

CTTCGCGGTCTTTCCAGTACTCTTGGATCGGAAACCCGTCGGCCTCCGAACGGTAAG AGCCTAGCA

TGTAGAACTGGTTGACGGCCTGGTAGGCGCAGCATCCCTTTTCTACGGGTAGCGCGT ATGCCTGCG

CGGCCTTCCGGAGCGAGGTGTGGGTGAGCGCAAAGGTGTCCCTGACCATGACCAGCA TGAAGGGC

ACGAGCTGCTTCCCAAAGGCCCCCATCCAAGTATAGGTCTCTACATCGTAGGTGACA AAGAGACG

CTCGGTGCGAGGATGCGAGCCGATCGGGAAGAACTGGATCTCCCGCCACCAATTGGA GGAGTGGC

TATTGATGTGGTGAAAGTAGAAGTCCCTGCGACGGGCCGAACACTCGTGCTGGCTTT TGTAAAAAC

GTGCGCAGTACTGGCAGCGGTGCACGGGCTGTACATCCTGCACGAGGTTGACCTGAC GACCGCGC

ACAAGGAAGCAGAGTGGGAATTTGAGCCCCTCGCCTGGCGGGTTTGGCTGGTGGTCT TCTACTTCG

GCTGCTTGTCCTTGACCGTCTGGCTGCTCGAGGGGAGTTACGGTGGATCGGACCACC ACGCCGCGC

GAGCCCAAAGTCCAGATGTCCGCGCGCGGCGGTCGGAGCTTGATGACAACATCGCGC AGATGGGA

GCTGTCCATGGTCTGGAGCTCCCGCGGCGTCAGGTCAGGCGGGAGCTCCTGCAGGTT TACCTCGCA

TAGACGGGTCAGGGCGCGGGCTAGATCCAGGTGATACCTAATTTCCAGGGGCTGGTT GGTGGCGG

CGTCGATGGCTTGCAAGAGGCCGCATCCCCGCGGCGCGACTACGGTACCGCGCGGCG GGCGGTGG

GCCGCGGGGGTGTCCTTGGATGATGCATCTAAAAGCGGTGACGCGGGCGAGCCCCCG GAGGTAGG

GGGGGCTCCGGACCCGCCGGGAGAGGGGGCAGGGGCACGTCGGCGCCGCGCGCGGGC AGGAGCT

GGTGCTGCGCGCGTAGGTTGCTGGCGAACGCGACGACGCGGCGGTTGATCTCCTGAA TCTGGCGC

CTCTGCGTGAAGACGACGGGCCCGGTGAGCTTGAACCTGAAAGAGAGTTCGACAGAA TCAATTTC

GGTGTCGTTGACGGCGGCCTGGCGCAAAATCTCCTGCACGTCTCCTGAGTTGTCTTG ATAGGCGAT

CTCGGCCATGAACTGCTCGATCTCTTCCTCCTGGAGATCTCCGCGTCCGGCTCGCTC CACGGTGGC

GGCGAGGTCGTTGGAAATGCGGGCCATGAGCTGCGAGAAGGCGTTGAGGCCTCCCTC GTTCCAGA

CGCGGCTGTAGACCACGCCCCCTTCGGCATCGCGGGCGCGCATGACCACCTGCGCGA GATTGAGC

TCCACGTGCCGGGCGAAGACGGCGTAGTTTCGCAGGCGCTGAAAGAGGTAGTTGAGG GTGGTGGC

GGTGTGTTCTGCCACGAAGAAGTACATAACCCAGCGTCGCAACGTGGATTCGTTGAT ATCCCCCAA

GGCCTCAAGGCGCTCCATGGCCTCGTAGAAGTCCACGGCGAAGTTGAAAAACTGGGA GTTGCGCG

CCGACACGGTTAACTCCTCCTCCAGAAGACGGATGAGCTCGGCGACAGTGTCGCGCA CCTCGCGCT

CAAAGGCTACAGGGGCCTCTTCTTCTTCTTCAATCTCCTCTTCCATAAGGGCCTCCC CTTCTTCTTCT

TCTGGCGGCGGTGGGGGAGGGGGGACACGGCGGCGACGACGGCGCACCGGGAGGCGG TCGACAA

AGCGCTCGATCATCTCCCCGCGGCGACGGCGCATGGTCTCGGTGACGGCGCGGCCGT TCTCGCGGG GGCGCAGTTGGAAGACGCCGCCCGTCATGTCCCGGTTATGGGTTGGCGGGGGGCTGCCAT GCGGC

AGGGATACGGCGCTAACGATGCATCTCAACAATTGTTGTGTAGGTACTCCGCCGCCG AGGGACCT

GAGCGAGTCCGCATCGACCGGATCGGAAAACCTCTCGAGAAAGGCGTCTAACCAGTC ACAGTCGC

AAGGTAGGCTGAGCACCGTGGCGGGCGGCAGCGGGCGGCGGTCGGGGTTGTTTCTGG CGGAGGTG

CTGCTGATGATGTAATTAAAGTAGGCGGTCTTGAGACGGCGGATGGTCGACAGAAGC ACCATGTC

CTTGGGTCCGGCCTGCTGAATGCGCAGGCGGTCGGCCATGCCCCAGGCTTCGTTTTG ACATCGGCG

CAGGTCTTTGTAGTAGTCTTGCATGAGCCTTTCTACCGGCACTTCTTCTTCTCCTTC CTCTTGTCCTG

CATCTCTTGCATCTATCGCTGCGGCGGCGGCGGAGTTTGGCCGTAGGTGGCGCCCTC TTCCTCCCAT

GCGTGTGACCCCGAAGCCCCTCATCGGCTGAAGCAGGGCTAGGTCGGCGACAACGCG CTCGGCTA

ATATGGCCTGCTGCACCTGCGTGAGGGTAGACTGGAAGTCATCCATGTCCACAAAGC GGTGGTAT

GCGCCCGTGTTGATGGTGTAAGTGCAGTTGGCCATAACGGACCAGTTAACGGTCTGG TGACCCGGC

TGCGAGAGCTCGGTGTACCTGAGACGCGAGTAAGCCCTCGAGTCAAATACGTAGTCG TTGCAAGT

CCGCACCAGGTACTGGTATCCCACCAAAAAGTGCGGCGGCGGCTGGCGGTAGAGGGG CCAGCGTA

GGGTGGCCGGGGCTCCGGGGGCGAGATCTTCCAACATAAGGCGATGATATCCGTAGA TGTACCTG

GACATCCAGGTGATGCCGGCGGCGGTGGTGGAGGCGCGCGGAAAGTCGCGGACGCGG TTCCAGAT

GTTGCGCAGCGGCAAAAAGTGCTCCATGGTCGGGACGCTCTGGCCGGTCAGGCGCGC GCAATCGT

TGACGCTCTAGACCGTGCAAAAGGAGAGCCTGTAAGCGGGCACTCTTCCGTGGTCTG GTGGATAA

ATTCGCAAGGGTATCATGGCGGACGACCGGGGTTCGAGCCCCGTATCCGGCCGTCCG CCGTGATCC

ATGCGGTTACCGCCCGCGTGTCGAACCCAGGTGTGCGACGTCAGACAACGGGGGAGT GCTCCTTTT

GGCTTCCTTCCAGGCGCGGCGGCTGCTGCGCTAGCTTTTTTGGCCACTGGCCGCGCG CAGCGTAAG

CGGTTAGGCTGGAAAGCGAAAGCATTAAGTGGCTCGCTCCCTGTAGCCGGAGGGTTA TTTTCCAAG

GGTTGAGTCGCGGGACCCCCGGTTCGAGTCTCGGACCGGCCGGACTGCGGCGAACGG GGGTTTGC

CTCCCCGTCATGCAAGACCCCGCTTGCAAATTCCTCCGGAAACAGGGACGAGCCCCT TTTTTGCTT

TTCCCAGATGCATCCGGTGCTGCGGCAGATGCGCCCCCCTCCTCAGCAGCGGCAAGA GCAAGAGC

AGCGGCAGACATGCAGGGCACCCTCCCCTCCTCCTACCGCGTCAGGAGGGGCGACAT CCGCGGTT

GACGCGGCAGCAGATGGTGATTACGAACCCCCGCGGCGCCGGGCCCGGCACTACCTG GACTTGGA

GGAGGGCGAGGGCCTGGCGCGGCTAGGAGCGCCCTCTCCTGAGCGGCACCCAAGGGT GCAGCTGA

AGCGTGATACGCGTGAGGCGTACGTGCCGCGGCAGAACCTGTTTCGCGACCGCGAGG GAGAGGAG

CCCGAGGAGATGCGGGATCGAAAGTTCCACGCAGGGCGCGAGCTGCGGCATGGCCTG AATCGCGA

GCGGTTGCTGCGCGAGGAGGACTTTGAGCCCGACGCGCGAACCGGGATTAGTCCCGC GCGCGCAC

ACGTGGCGGCCGCCGACCTGGTAACCGCATACGAGCAGACGGTGAACCAGGAGATTA ACTTTCAA

AAAAGCTTTAACAACCACGTGCGTACGCTTGTGGCGCGCGAGGAGGTGGCTATAGGA CTGATGCA

TCTGTGGGACTTTGTAAGCGCGCTGGAGCAAAACCCAAATAGCAAGCCGCTCATGGC GCAGCTGT

TCCTTATAGTGCAGCACAGCAGGGACAACGAGGCATTCAGGGATGCGCTGCTAAACA TAGTAGAG

CCCGAGGGCCGCTGGCTGCTCGATTTGATAAACATCCTGCAGAGCATAGTGGTGCAG GAGCGCAG

CTTGAGCCTGGCTGACAAGGTGGCCGCCATCAACTATTCCATGCTTAGCCTGGGCAA GTTTTACGC

CCGCAAGATATACCATACCCCTTACGTTCCCATAGACAAGGAGGTAAAGATCGAGGG GTTCTACA

TGCGCATGGCGCTGAAGGTGCTTACCTTGAGCGACGACCTGGGCGTTTATCGCAACG AGCGCATCC

ACAAGGCCGTGAGCGTGAGCCGGCGGCGCGAGCTCAGCGACCGCGAGCTGATGCACA GCCTGCAA

AGGGCCCTGGCTGGCACGGGCAGCGGCGATAGAGAGGCCGAGTCCTACTTTGACGCG GGCGCTGA

CCTGCGCTGGGCCCCAAGCCGACGCGCCCTGGAGGCAGCTGGGGCCGGACCTGGGCT GGCGGTGG

CACCCGCGCGCGCTGGCAACGTCGGCGGCGTGGAGGAATATGACGAGGACGATGAGT ACGAGCC

AGAGGACGGCGAGTACTAAGCGGTGATGTTTCTGATCAGATGATGCAAGACGCAACG GACCCGGC

GGTGCGGGCGGCGCTGCAGAGCCAGCCGTCCGGCCTTAACTCCACGGACGACTGGCG CCAGGTCA

TGGACCGCATCATGTCGCTGACTGCGCGCAATCCTGACGCGTTCCGGCAGCAGCCGC AGGCCAAC

CGGCTCTCCGCAATTCTGGAAGCGGTGGTCCCGGCGCGCGCAAACCCCACGCACGAG AAGGTGCT

GGCGATCGTAAACGCGCTGGCCGAAAACAGGGCCATCCGGCCCGACGAGGCCGGCCT GGTCTACG

ACGCGCTGCTTCAGCGCGTGGCTCGTTACAACAGCGGCAACGTGCAGACCAACCTGG ACCGGCTG

GTGGGGGATGTGCGCGAGGCCGTGGCGCAGCGTGAGCGCGCGCAGCAGCAGGGCAAC CTGGGCT

CCATGGTTGCACTAAACGCCTTCCTGAGTACACAGCCCGCCAACGTGCCGCGGGGAC AGGAGGAC

TACACCAACTTTGTGAGCGCACTGCGGCTAATGGTGACTGAGACACCGCAAAGTGAG GTGTACCA

GTCTGGGCCAGACTATTTTTTCCAGACCAGTAGACAAGGCCTGCAGACCGTAAACCT GAGCCAGG

CTTTCAAAAACTTGCAGGGGCTGTGGGGGGTGCGGGCTCCCACAGGCGACCGCGCGA CCGTGTCT

AGCTTGCTGACGCCCAACTCGCGCCTGTTGCTGCTGCTAATAGCGCCCTTCACGGAC AGTGGCAGC

GTGTCCCGGGACACATACCTAGGTCACTTGCTGACACTGTACCGCGAGGCCATAGGT CAGGCGCAT

GTGGACGAGCATACTTTCCAGGAGATTACAAGTGTCAGCCGCGCGCTGGGGCAGGAG GACACGGG

CAGCCTGGAGGCAACCCTAAACTACCTGCTGACCAACCGGCGGCAGAAGATCCCCTC GTTGCACA

GTTTAAACAGCGAGGAGGAGCGCATTTTGCGCTACGTGCAGCAGAGCGTGAGCCTTA ACCTGATG

CGCGACGGGGTAACGCCCAGCGTGGCGCTGGACATGACCGCGCGCAACATGGAACCG GGCATGTA TGCCTCAAACCGGCCGTTTATCAACCGCCTAATGGACTACTTGCATCGCGCGGCCGCCGT GAACCC

CGAGTATTTCACCAATGCCATCTTGAACCCGCACTGGCTACCGCCCCCTGGTTTCTA CACCGGGGG

ATTCGAGGTGCCCGAGGGTAACGATGGATTCCTCTGGGACGACATAGACGACAGCGT GTTTTCCCC

GCAACCGCAGACCCTGCTAGAGTTGCAACAGCGCGAGCAGGCAGAGGCGGCGCTGCG AAAGGAA

AGCTTCCGCAGGCCAAGCAGCTTGTCCGATCTAGGCGCTGCGGCCCCGCGGTCAGAT GCTAGTAGC

CCATTTCCAAGCTTGATAGGGTCTCTTACCAGCACTCGCACCACCCGCCCGCGCCTG CTGGGCGAG

GAGGAGTACCTAAACAACTCGCTGCTGCAGCCGCAGCGCGAAAAAAACCTGCCTCCG GCATTTCC

CAACAACGGGATAGAGAGCCTAGTGGACAAGATGAGTAGATGGAAGACGTACGCGCA GGAGCAC

AGGGACGTGCCAGGCCCGCGCCCGCCCACCCGTCGTCAAAGGCACGACCGTCAGCGG GGTCTGGT

GTGGGAGGACGATGACTCGGCAGACGACAGCAGCGTCCTGGATTTGGGAGGGAGTGG CAACCCGT

TTGCGCACCTTCGCCCCAGGCTGGGGAGAATGTTTTAAAAAAAAAAAAAGCATGATG CAAAATAA

AAAACTCACCAAGGCCATGGCACCGAGCGTTGGTTTTCTTGTATTCCCCTTAGTATG CGGCGCGCG

GCGATGTATGAGGAAGGTCCTCCTCCCTCCTACGAGAGTGTGGTGAGCGCGGCGCCA GTGGCGGC

GGCGCTGGGTTCTCCCTTCGATGCTCCCCTGGACCCGCCGTTTGTGCCTCCGCGGTA CCTGCGGCCT

ACCGGGGGGAGAAACAGCATCCGTTACTCTGAGTTGGCACCCCTATTCGACACCACC CGTGTGTAC

CTGGTGGACAACAAGTCAACGGATGTGGCATCCCTGAACTACCAGAACGACCACAGC AACTTTCT

GACCACGGTCATTCAAAACAATGACTACAGCCCGGGGGAGGCAAGCACACAGACCAT CAATCTTG

ACGACCGGTCGCACTGGGGCGGCGACCTGAAAACCATCCTGCATACCAACATGCCAA ATGTGAAC

GAGTTCATGTTTACCAATAAGTTTAAGGCGCGGGTGATGGTGTCGCGCTTGCCTACT AAGGACAAT

CAGGTGGAGCTGAAATACGAGTGGGTGGAGTTCACGCTGCCCGAGGGCAACTACTCC GAGACCAT

GACCATAGACCTTATGAACAACGCGATCGTGGAGCACTACTTGAAAGTGGGCAGACA GAACGGGG

TTCTGGAAAGCGACATCGGGGTAAAGTTTGACACCCGCAACTTCAGACTGGGGTTTG ACCCCGTCA

CTGGTCTTGTCATGCCTGGGGTATATACAAACGAAGCCTTCCATCCAGACATCATTT TGCTGCCAG

GATGCGGGGTGGACTTCACCCACAGCCGCCTGAGCAACTTGTTGGGCATCCGCAAGC GGCAACCC

TTCCAGGAGGGCTTTAGGATCACCTACGATGATCTGGAGGGTGGTAACATTCCCGCA CTGTTGGAT

GTGGACGCCTACCAGGCGAGCTTGAAAGATGACACCGAACAGGGCGGGGGTGGCGCA GGCGGCA

GCAACAGCAGTGGCAGCGGCGCGGAAGAGAACTCCAACGCGGCAGCCGCGGCAATGC AGCCGGT

GGAGGACATGAACGATCATGCCATTCGCGGCGACACCTTTGCCACACGGGCTGAGGA GAAGCGCG

CTGAGGCCGAAGCAGCGGCCGAAGCTGCCGCCCCCGCTGCGCAACCCGAGGTCGAGA AGCCTCAG

AAGAAACCGGTGATCAAACCCCTGACAGAGGACAGCAAGAAACGCAGTTACAACCTA ATAAGCA

ATGACAGCACCTTCACCCAGTACCGCAGCTGGTACCTTGCATACAACTACGGCGACC CTCAGACCG

GAATCCGCTCATGGACCCTGCTTTGCACTCCTGACGTAACCTGCGGCTCGGAGCAGG TCTACTGGT

CGTTGCCAGACATGATGCAAGACCCCGTGACCTTCCGCTCCACGCGCCAGATCAGCA ACTTTCCGG

TGGTGGGCGCCGAGCTGTTGCCCGTGCACTCCAAGAGCTTCTACAACGACCAGGCCG TCTACTCCC

AACTCATCCGCCAGTTTACCTCTCTGACCCACGTGTTCAATCGCTTTCCCGAGAACC AGATTTTGGC

GCGCCCGCCAGCCCCCACCATCACCACCGTCAGTGAAAACGTTCCTGCTCTCACAGA TCACGGGAC

GCTACCGCTGCGCAACAGCATCGGAGGAGTCCAGCGAGTGACCATTACTGACGCCAG ACGCCGCA

CCTGCCCCTACGTTTACAAGGCCCTGGGCATAGTCTCGCCGCGCGTCCTATCGAGCC GCACTTTTTG

AGCAAGCATGTCCATCCTTATATCGCCCAGCAATAACACAGGCTGGGGCCTGCGCTT CCCAAGCAA

GATGTTTGGCGGGGCCAAGAAGCGCTCCGACCAACACCCAGTGCGCGTGCGCGGGCA CTACCGCG

CGCCCTGGGGCGCGCACAAACGCGGCCGCACTGGGCGCACCACCGTCGATGACGCCA TCGACGCG

GTGGTGGAGGAGGCGCGCAACTACACGCCCACGCCGCCACCAGTGTCCACAGTGGAC GCGGCCAT

TCAGACCGTGGTGCGCGGAGCCCGGCGCTATGCTAAAATGAAGAGACGGCGGAGGCG CGTAGCAC

GTCGCCACCGCCGCCGACCCGGCACTGCCGCCCAACGCGCGGCGGCGGCCCTGCTTA ACCGCGCA

CGTCGCACCGGCCGACGGGCGGCCATGCGGGCCGCTCGAAGGCTGGCCGCGGGTATT GTCACTGT

GCCCCCCAGGTCCAGGCGACGAGCGGCCGCCGCAGCAGCCGCGGCCATTAGTGCTAT GACTCAGG

GTCGCAGGGGCAACGTGTATTGGGTGCGCGACTCGGTTAGCGGCCTGCGCGTGCCCG TGCGCACC

CGCCCCCCGCGC A ACT AG ATTGC A AG A A A A A ACT ACTT AG ACTCGT ACTGTTGT ATGT ATCC AGCG

GCGGCGGCGCGCAACGAAGCTATGTCCAAGCGCAAAATCAAAGAAGAGATGCTCCAG GTCATCGC

GCCGGAGATCTATGGCCCCCCGAAGAAGGAAGAGCAGGATTACAAGCCCCGAAAGCT AAAGCGG

GTCAAAAAGAAAAAGAAAGATGATGATGATGAACTTGACGACGAGGTGGAACTGCTG CACGCTA

CCGCGCCCAGGCGACGGGTACAGTGGAAAGGTCGACGCGTAAAACGTGTTTTGCGAC CCGGCACC

ACCGTAGTCTTTACGCCCGGTGAGCGCTCCACCCGCACCTACAAGCGCGTGTATGAT GAGGTGTAC

GGCGACGAGGACCTGCTTGAGCAGGCCAACGAGCGCCTCGGGGAGTTTGCCTACGGA AAGCGGCA

TAAGGACATGCTGGCGTTGCCGCTGGACGAGGGCAACCCAACACCTAGCCTAAAGCC CGTAACAC

TGCAGCAGGTGCTGCCCGCGCTTGCACCGTCCGAAGAAAAGCGCGGCCTAAAGCGCG AGTCTGGT

GACTTGGCACCCACCGTGCAGCTGATGGTACCCAAGCGCCAGCGACTGGAAGATGTC TTGGAAAA

AATGACCGTGGAACCTGGGCTGGAGCCCGAGGTCCGCGTGCGGCCAATCAAGCAGGT GGCGCCGG

GACTGGGCGTGCAGACCGTGGACGTTCAGATACCCACTACCAGTAGCACCAGTATTG CCACCGCC ACAGAGGGCATGGAGACACAAACGTCCCCGGTTGCCTCAGCGGTGGCGGATGCCGCGGTG CAGGC

GGTCGCTGCGGCCGCGTCCAAGACCTCTACGGAGGTGCAAACGGACCCGTGGATGTT TCGCGTTTC

AGCCCCCCGGCGCCCGCGCCGTTCGAGGAAGTACGGCGCCGCCAGCGCGCTACTGCC CGAATATG

CCCTACATCCTTCCATTGCGCCTACCCCCGGCTATCGTGGCTACACCTACCGCCCCA GAAGACGAG

CAACTACCCGACGCCGAACCACCACTGGAACCCGCCGCCGCCGTCGCCGTCGCCAGC CCGTGCTG

GCCCCGATTTCCGTGCGCAGGGTGGCTCGCGAAGGAGGCAGGACCCTGGTGCTGCCA ACAGCGCG

CTACCACCCCAGCATCGTTTAAAAGCCGGTCTTTGTGGTTCTTGCAGATATGGCCCT CACCTGCCGC

CTCCGTTTCCCGGTGCCGGGATTCCGAGGAAGAATGCACCGTAGGAGGGGCATGGCC GGCCACGG

CCTGACGGGCGGCATGCGTCGTGCGCACCACCGGCGGCGGCGCGCGTCGCACCGTCG CATGCGCG

GCGGTATCCTGCCCCTCCTTATTCCACTGATCGCCGCGGCGATTGGCGCCGTGCCCG GAATTGCAT

CCGTGGCCTTGCAGGCGCAGAGACACTGATTAAAAACAAGTTGCATGTGGAAAAATC AAAATAAA

AAGTCTGGACTCTCACGCTCGCTTGGTCCTGTAACTATTTTGTAGAATGGAAGACAT CAACTTTGC

GTCTCTGGCCCCGCGACACGGCTCGCGCCCGTTCATGGGAAACTGGCAAGATATCGG CACCAGCA

ATATGAGCGGTGGCGCCTTCAGCTGGGGCTCGCTGTGGAGCGGCATTAAAAATTTCG GTTCCACCG

TTAAGAACTATGGCAGCAAGGCCTGGAACAGCAGCACAGGCCAGATGCTGAGGGATA AGTTGAA

AGAGCAAAATTTCCAACAAAAGGTGGTAGATGGCCTGGCCTCTGGCATTAGCGGGGT GGTGGACC

TGGCCAACCAGGCAGTGCAAAATAAGATTAACAGTAAGCTTGATCCCCGCCCTCCCG TAGAGGAG

CCTCCACCGGCCGTGGAGACAGTGTCTCCAGAGGGGCGTGGCGAAAAGCGTCCGCGC CCCGACAG

GGAAGAAACTCTGGTGACGCAAATAGACGAGCCTCCCTCGTACGAGGAGGCACTAAA GCAAGGCC

TGCCCACCACCCGTCCCATCGCGCCCATGGCTACCGGAGTGCTGGGCCAGCACACAC CCGTAACGC

TGGACCTGCCTCCCCCCGCCGACACCCAGCAGAAACCTGTGCTGCCAGGCCCGACCG CCGTTGTTG

TAACCCGTCCTAGCCGCGCGTCCCTGCGCCGCGCCGCCAGCGGTCCGCGATCGTTGC GGCCCGTAG

CCAGTGGCAACTGGCAAAGCACACTGAACAGCATCGTGGGTCTGGGGGTGCAATCCC TGAAGCGC

CGACGATGCTTCTGATAGCTAACGTGTCGTATGTGTGTCATGTATGCGTCCATGTCG CCGCCAGAG

GAGCTGCTGAGCCGCCGCGCGCCCGCTTTCCAAGATGGCTACCCCTTCGATGATGCC GCAGTGGTC

TTACATGCACATCTCGGGCCAGGACGCCTCGGAGTACCTGAGCCCCGGGCTGGTGCA GTTTGCCCG

CGCCACCGAGACGTACTTCAGCCTGAATAACAAGTTTAGAAACCCCACGGTGGCGCC TACGCACG

ACGTGACCACAGACCGGTCCCAGCGTTTGACGCTGCGGTTCATCCCTGTGGACCGTG AGGATACTG

CGTACTCGTACAAGGCGCGGTTCACCCTAGCTGTGGGTGATAACCGTGTGCTGGACA TGGCTTCCA

CGTACTTTGACATCCGCGGCGTGCTGGACAGGGGCCCTACTTTTAAGCCCTACTCTG GCACTGCCT

ACAACGCCCTGGCTCCCAAGGGTGCCCCAAATCCTTGCGAATGGGATGAAGCTGCTA CTGCTCTTG

AAATAAACCTAGAAGAAGAGGACGATGACAACGAAGACGAAGTAGACGAGCAAGCTG AGCAGCA

A A A A ACTC ACGT ATTTGGGC AGGCGCCTT ATTCTGGT AT AA AT ATT AC A A AGG AGGGT ATTC A A AT

AGGTGTCGAAGGTCAAACACCTAAATATGCCGATAAAACATTTCAACCTGAACCTCA AATAGGAG

AATCTCAGTGGTACGAAACAGAAATTAATCATGCAGCTGGGAGAGTCCTAAAAAAGA CTACCCCA

ATGAAACCATGTTACGGTTCATATGCAAAACCCACAAATGAAAATGGAGGGCAAGGC ATTCTTGT

AAAGCAACAAAATGGAAAGCTAGAAAGTCAAGTGGAAATGCAATTTTTCTCAACTAC TGAGGCAG

CCGCAGGCAATGGTGATAACTTGACTCCTAAAGTGGTATTGTACAGTGAAGATGTAG ATATAGAA

ACCCCAGACACTCATATTTCTTACATGCCCACTATTAAGGAAGGTAACTCACGAGAA CTAATGGGC

C A AC A ATCT ATGCCC A AC AGGCCT A ATT AC ATTGCTTTT AGGG AC A ATTTT ATTGGTCT AATGT ATT

ACAACAGCACGGGTAATATGGGTGTTCTGGCGGGCCAAGCATCGCAGTTGAATGCTG TTGTAGATT

TGCAAGACAGAAACACAGAGCTTTCATACCAGCTTTTGCTTGATTCCATTGGTGATA GAACCAGGT

ACTTTTCTATGTGGAATCAGGCTGTTGACAGCTATGATCCAGATGTTAGAATTATTG AAAATCATG

GAACTGAAGATGAACTTCCAAATTACTGCTTTCCACTGGGAGGTGTGATTAATACAG AGACTCTTA

CCAAGGTAAAACCTAAAACAGGTCAGGAAAATGGATGGGAAAAAGATGCTACAGAAT TTTCAGAT

AAAAATGAAATAAGAGTTGGAAATAATTTTGCCATGGAAATCAATCTAAATGCCAAC CTGTGGAG

A A ATTTCCTGT ACTCC A AC AT AGCGCTGT ATTTGCCCG AC A AGCT A A AGT AC AGTCCTTCC A ACGT

AAAAATTTCTGATAACCCAAACACCTACGACTACATGAACAAGCGAGTGGTGGCTCC CGGGCTAG

TGGACTGCTACATTAACCTTGGAGCACGCTGGTCCCTTGACTATATGGACAACGTCA ACCCATTTA

ACCACCACCGCAATGCTGGCCTGCGCTACCGCTCAATGTTGCTGGGCAATGGTCGCT ATGTGCCCT

TCCACATCCAGGTGCCTCAGAAGTTCTTTGCCATTAAAAACCTCCTTCTCCTGCCGG GCTCATACAC

CTACGAGTGGAACTTCAGGAAGGATGTTAACATGGTTCTGCAGAGCTCCCTAGGAAA TGACCTAA

GGGTTGACGGAGCCAGCATTAAGTTTGATAGCATTTGCCTTTACGCCACCTTCTTCC CCATGGCCC

ACAACACCGCCTCCACGCTTGAGGCCATGCTTAGAAACGACACCAACGACCAGTCCT TTAACGACT

ATCTCTCCGCCGCC A AC ATGCTCT ACCCT AT ACCCGCC A ACGCT ACC A ACGTGCCC AT ATCC ATCC

CCTCCCGCAACTGGGCGGCTTTCCGCGGCTGGGCCTTCACGCGCCTTAAGACTAAGG AAACCCCAT

C ACTGGGCTCGGGCT ACG ACCCTT ATT AC ACCT ACTCTGGCTCT AT ACCCT ACCT AG ATGG A ACCTT

TTACCTCAACCACACCTTTAAGAAGGTGGCCATTACCTTTGACTCTTCTGTCAGCTG GCCTGGCAAT

GACCGCCTGCTTACCCCCAACGAGTTTGAAATTAAGCGCTCAGTTGACGGGGAGGGT TACAACGTT GCCCAGTGTAACATGACCAAAGACTGGTTCCTGGTACAAATGCTAGCTAACTATAACATT GGCTAC

C AGGGCTTCT AT ATCCC AG AG AGCT AC A AGG ACCGC ATGT ACTCCTTCTTT AG A A ACTTCC AGCCC

ATGAGCCGTCAGGTGGTGGATGATACTAAATACAAGGACTACCAACAGGTGGGCATC CTACACCA

ACACAACAACTCTGGATTTGTTGGCTACCTTGCCCCCACCATGCGCGAAGGACAGGC CTACCCTGC

T AACTTCCCCT ATCCGCTT AT AGGC A AG ACCGC AGTTG AC AGC ATT ACCC AG A A A A AGTTTCTTTG

CGATCGCACCCTTTGGCGCATCCCATTCTCCAGTAACTTTATGTCCATGGGCGCACT CACAGACCT

GGGCCAAAACCTTCTCTACGCCAACTCCGCCCACGCGCTAGACATGACTTTTGAGGT GGATCCCAT

GGACGAGCCCACCCTTCTTTATGTTTTGTTTGAAGTCTTTGACGTGGTCCGTGTGCA CCAGCCGCAC

CGCGGCGTCATCGAAACCGTGTACCTGCGCACGCCCTTCTCGGCCGGCAACGCCACA ACATAAAG

AAGCAAGCAACATCAACAACAGCTGCCGCCATGGGCTCCAGTGAGCAGGAACTGAAA GCCATTGT

CAAAGATCTTGGTTGTGGGCCATATTTTTTGGGCACCTATGACAAGCGCTTTCCAGG CTTTGTTTCT

CCACACAAGCTCGCCTGCGCCATAGTCAATACGGCCGGTCGCGAGACTGGGGGCGTA CACTGGAT

GGCCTTTGCCTGGAACCCGCACTCAAAAACATGCTACCTCTTTGAGCCCTTTGGCTT TTCTGACCAG

CGACTCAAGCAGGTTTACCAGTTTGAGTACGAGTCACTCCTGCGCCGTAGCGCCATT GCTTCTTCC

CCCGACCGCTGTATAACGCTGGAAAAGTCCACCCAAAGCGTACAGGGGCCCAACTCG GCCGCCTG

TGGACTATTCTGCTGCATGTTTCTCCACGCCTTTGCCAACTGGCCCCAAACTCCCAT GGATCACAAC

CCCACCATGAACCTTATTACCGGGGTACCCAACTCCATGCTCAACAGTCCCCAGGTA CAGCCCACC

CTGCGTCGCAACCAGGAACAGCTCTACAGCTTCCTGGAGCGCCACTCGCCCTACTTC CGCAGCCAC

AGTGCGCAGATTAGGAGCGCCACTTCTTTTTGTCACTTGAAAAACATGTAAAAATAA TGTACTAGA

GACACTTTCAATAAAGGCAAATGCTTTTATTTGTACACTCTCGGGTGATTATTTACC CCCACCCTTG

CCGTCTGCGCCGTTTAAAAATCAAAGGGGTTCTGCCGCGCATCGCTATGCGCCACTG GCAGGGACA

CGTTGCGATACTGGTGTTTAGTGCTCCACTTAAACTCAGGCACAACCATCCGCGGCA GCTCGGTGA

AGTTTTCACTCCACAGGCTGCGCACCATCACCAACGCGTTTAGCAGGTCGGGCGCCG ATATCTTGA

AGTCGCAGTTGGGGCCTCCGCCCTGCGCGCGCGAGTTGCGATACACAGGGTTGCAGC ACTGGAAC

ACTATCAGCGCCGGGTGGTGCACGCTGGCCAGCACGCTCTTGTCGGAGATCAGATCC GCGTCCAG

GTCCTCCGCGTTGCTCAGGGCGAACGGAGTCAACTTTGGTAGCTGCCTTCCCAAAAA GGGCGCGTG

CCCAGGCTTTGAGTTGCACTCGCACCGTAGTGGCATCAAAAGGTGACCGTGCCCGGT CTGGGCGTT

AGGATACAGCGCCTGCATAAAAGCCTTGATCTGCTTAAAAGCCACCTGAGCCTTTGC GCCTTCAGA

GAAGAACATGCCGCAAGACTTGCCGGAAAACTGATTGGCCGGACAGGCCGCGTCGTG CACGCAGC

ACCTTGCGTCGGTGTTGGAGATCTGCACCACATTTCGGCCCCACCGGTTCTTCACGA TCTTGGCCTT

GCTAGACTGCTCCTTCAGCGCGCGCTGCCCGTTTTCGCTCGTCACATCCATTTCAAT CACGTGCTCC

TTATTTATCATAATGCTTCCGTGTAGACACTTAAGCTCGCCTTCGATCTCAGCGCAG CGGTGCAGCC

ACAACGCGCAGCCCGTGGGCTCGTGATGCTTGTAGGTCACCTCTGCAAACGACTGCA GGTACGCCT

GCAGGAATCGCCCCATCATCGTCACAAAGGTCTTGTTGCTGGTGAAGGTCAGCTGCA ACCCGCGGT

GCTCCTCGTTCAGCCAGGTCTTGCATACGGCCGCCAGAGCTTCCACTTGGTCAGGCA GTAGTTTGA

AGTTCGCCTTTAGATCGTTATCCACGTGGTACTTGTCCATCAGCGCGCGCGCAGCCT CCATGCCCTT

CTCCCACGCAGACACGATCGGCACACTCAGCGGGTTCATCACCGTAATTTCACTTTC CGCTTCGCT

GGGCTCTTCCTCTTCCTCTTGCGTCCGCATACCACGCGCCACTGGGTCGTCTTCATT CAGCCGCCGC

ACTGTGCGCTTACCTCCTTTGCCATGCTTGATTAGCACCGGTGGGTTGCTGAAACCC ACCATTTGTA

GCGCC AC ATCTTCTCTTTCTTCCTCGCTGTCC ACG ATT ACTTG AC A ATT A ATC ATCGGCTCGT AT A A

TGATGCAGTACATTTTCACAGGAGGTACAGCTATGACCATGATTACGGATTCACTGG CCGTCGTTT

TACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCAC ATCCCCCTT

TCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGC GCAGCCTG

AATGGCGAATAGGTCGCGCCGCACCGCGTCCGCGCTCGGGGGTGGTTTCGCGCTGCT CCTCTTCCC

GACTGGCCATTTCCTTCTCCTATAGGCAGAAAAAGATCATGGAGTCAGTCGAGAAGA AGGACAGC

CTAACCGCCCCCTCTGAGTTCGCCACCACCGCCTCCACCGATGCCGCCAACGCGCCT ACCACCTTC

CCCGTCGAGGCACCCCCGCTTGAGGAGGAGGAAGTGATTATCGAGCAGGACCCAGGT TTTGTAAG

CGAAGACGACGAGGACCGCTCAGTACCAACAGAGGATAAAAAGCAAGACCAGGACAA CGCAGAG

GCAAACGAGGAACAAGTCGGGCGGGGGGACGAAAGGCATGGCGACTACCTAGATGTG GGAGACG

ACGTGCTGTTGAAGCATCTGCAGCGCCAGTGCGCCATTATCTGCGACGCGTTGCAAG AGCGCAGC

GATGTGCCCCTCGCCATAGCGGATGTCAGCCTTGCCTACGAACGCCACCTATTCTCA CCGCGCGTA

CCCCCCAAACGCCAAGAAAACGGCACATGCGAGCCCAACCCGCGCCTCAACTTCTAC CCCGTATTT

GCCGTGCCAGAGGTGCTTGCCACCTATCACATCTTTTTCCAAAACTGCAAGATACCC CTATCCTGC

CGTGCCAACCGCAGCCGAGCGGACAAGCAGCTGGCCTTGCGGCAGGGCGCTGTCATA CCTGATAT

CGCCTCGCTCAACGAAGTGCCAAAAATCTTTGAGGGTCTTGGACGCGACGAGAAGCG CGCGGCAA

ACGCTCTGCAACAGGAAAACAGCGAAAATGAAAGTCACTCTGGAGTGTTGGTGGAAC TCGAGGGT

GACAACGCGCGCCTAGCCGTACTAAAACGCAGCATCGAGGTCACCCACTTTGCCTAC CCGGCACTT

AACCTACCCCCCAAGGTCATGAGCACAGTCATGAGTGAGCTGATCGTGCGCCGTGCG CAGCCCCT

GGAGAGGGATGCAAATTTGCAAGAACAAACAGAGGAGGGCCTACCCGCAGTTGGCGA CGAGCAG CTAGCGCGCTGGCTTCAAACGCGCGAGCCTGCCGACTTGGAGGAGCGACGCAAACTAATG ATGGC

CGCAGTGCTCGTTACCGTGGAGCTTGAGTGCATGCAGCGGTTCTTTGCTGACCCGGA GATGCAGCG

CAAGCTAGAGGAAACATTGCACTACACCTTTCGACAGGGCTACGTACGCCAGGCCTG CAAGATCT

CCAACGTGGAGCTCTGCAACCTGGTCTCCTACCTTGGAATTTTGCACGAAAACCGCC TTGGGCAAA

ACGTGCTTCATTCCACGCTCAAGGGCGAGGCGCGCCGCGACTACGTCCGCGACTGCG TTTACTTAT

TTCTATGCTACACCTGGCAGACGGCCATGGGCGTTTGGCAGCAGTGCTTGGAGGAGT GCAACCTCA

AGGAGCTGCAGAAACTGCTAAAGCAAAACTTGAAGGACCTATGGACGGCCTTCAACG AGCGCTCC

GTGGCCGCGCACCTGGCGGACATCATTTTCCCCGAACGCCTGCTTAAAACCCTGCAA CAGGGTCTG

CCAGACTTCACCAGTCAAAGCATGTTGCAGAACTTTAGGAACTTTATCCTAGAGCGC TCAGGAATC

TTGCCCGCCACCTGCTGTGCACTTCCTAGCGACTTTGTGCCCATTAAGTACCGCGAA TGCCCTCCGC

CGCTTTGGGGCCACTGCTACCTTCTGCAGCTAGCCAACTACCTTGCCTACCACTCTG ACATAATGG

AAGACGTGAGCGGTGACGGTCTACTGGAGTGTCACTGTCGCTGCAACCTATGCACCC CGCACCGCT

CCCTGGTTTGCAATTCGCAGCTGCTTAACGAAAGTCAAATTATCGGTACCTTTGAGC TGCAGGGTC

CCTCGCCTGACGAAAAGTCCGCGGCTCCGGGGTTGAAACTCACTCCGGGGCTGTGGA CGTCGGCTT

ACCTTCGC A A ATTTGT ACCTG AGG ACT ACC ACGCCC ACG AG ATT AGGTTCT ACG A AG ACC A ATCCC

GCCCGCCTAATGCGGAGCTTACCGCCTGCGTCATTACCCAGGGCCACATTCTTGGCC AATTGCAAG

CCATCAACAAAGCCCGCCAAGAGTTTCTGCTACGAAAGGGACGGGGGGTTTACTTGG ACCCCCAG

TCCGGCGAGGAGCTCAACCCAATCCCCCCGCCGCCGCAGCCCTATCAGCAGCAGCCG CGGGCCCT

TGCTTCCCAGGATGGCACCCAAAAAGAAGCTGCAGCTGCCGCCGCCACCCACGGACG AGGAGGAA

TACTGGGACAGTCAGGCAGAGGAGGTTTTGGACGAGGAGGAGGAGGACATGATGGAA GACTGGG

AGAGCCTAGACGAGGAAGCTTCCGAGGTCGAAGAGGTGTCAGACGAAACACCGTCAC CCTCGGTC

GCATTCCCCTCGCCGGCGCCCCAGAAATCGGCAACCGGTTCCAGCATGGCTACAACC TCCGCTCCT

CAGGCGCCGCCGGCACTGCCCGTTCGCCGACCCAACCGTAGATGGGACACCACTGGA ACCAGGGC

CGGTAAGTCCAAGCAGCCGCCGCCGTTAGCCCAAGAGCAACAACAGCGCCAAGGCTA CCGCTCAT

GGCGCGGGCACAAGAACGCCATAGTTGCTTGCTTGCAAGACTGTGGGGGCAACATCT CCTTCGCCC

GCCGCTTTCTTCTCTACCATCACGGCGTGGCCTTCCCCCGTAACATCCTGCATTACT ACCGTCATCT

CTACAGCCCATACTGCACCGGCGGCAGCGGCAGCAACAGCAGCGGCCACACAGAAGC AAAGGCG

ACCGGATAGCAAGACTCTGACAAAGCCCAAGAAATCCACAGCGGCGGCAGCAGCAGG AGGAGGA

GCGCTGCGTCTGGCGCCCAACGAACCCGTATCGACCCGCGAGCTTAGAAACAGGATT TTTCCCACT

CTGTATGCTATATTTCAACAGAGCAGGGGCCAAGAACAAGAGCTGAAAATAAAAAAC AGGTCTCT

GCGATCCCTCACCCGCAGCTGCCTGTATCACAAAAGCGAAGATCAGCTTCGGCGCAC GCTGGAAG

ACGCGGAGGCTCTCTTCAGTAAATACTGCGCGCTGACTCTTAAGGACTAGTTTCGCG CCCTTTCTC

AAATTTAAGCGCGAAAACTACGTCATCTCCAGCGGCCACACCCGGCGCCAGCACCTG TTGTCAGC

GCCATTATGAGCAAGGAAATTCCCACGCCCTACATGTGGAGTTACCAGCCACAAATG GGACTTGC

GGCTGGAGCTGCCCAAGACTACTCAACCCGAATAAACTACATGAGCGCGGGACCCCA CATGATAT

CCCGGGTCAACGGAATACGCGCCCACCGAAACCGAATTCTCCTGGAACAGGCGGCTA TTACCACC

ACACCTCGTAATAACCTTAATCCCCGTAGTTGGCCCGCTGCCCTGGTGTACCAGGAA AGTCCCGCT

CCCACCACTGTGGTACTTCCCAGAGACGCCCAGGCCGAAGTTCAGATGACTAACTCA GGGGCGCA

GCTTGCGGGCGGCTTTCGTCACAGGGTGCGGTCGCCCGGGCAGGGTATAACTCACCT GACAATCA

GAGGGCGAGGTATTCAGCTCAACGACGAGTCGGTGAGCTCCTCGCTTGGTCTCCGTC CGGACGGG

ACATTTCAGATCGGCGGCGCCGGCCGCTCTTCATTCACGCCTCGTCAGGCAATCCTA ACTCTGCAG

ACCTCGTCCTCTGAGCCGCGCTCTGGAGGCATTGGAACTCTGCAATTTATTGAGGAG TTTGTGCCA

TCGGTCT ACTTT AACCCCTTCTCGGG ACCTCCCGGCC ACT ATCCGG ATC A ATTTATTCCT AACTTTG

ACGCGGTAAAGGACTCGGCGGACGGCTACGACTGAATGTTAAGTGGAGAGGCAGAGC AACTGCG

CCTGAAACACCTGGTCCACTGTCGCCGCCACAAGTGCTTTGCCCGCGACTCCGGTGA GTTTTGCTA

CTTTGAATTGCCCGAGGATCATATCGAGGGCCCGGCGCACGGCGTCCGGCTTACCGC CCAGGGAG

AGCTTGCCCGTAGCCTGATTCGGGAGTTTACCCAGCGCCCCCTGCTAGTTGAGCGGG ACAGGGGAC

CCTGTGTTCTCACTGTGATTTGCAACTGTCCTAACCCTGGATTACATCAAGATCTTT GTTGCCATCT

CTGTGCTGAGTATAATAAATACAGAAATTAAAATATACTGGGGCTCCTATCGCCATC CTGTAAACG

CCACCGTCTTCACCCGCCCAAGCAAACCAAGGCGAACCTTACCTGGTACTTTTAACA TCTCTCCCT

CTGTGATTTACAACAGTTTCAACCCAGACGGAGTGAGTCTACGAGAGAACCTCTCCG AGCTCAGCT

ACTCCATCAGAAAAAACACCACCCTCCTTACCTGCCGGGAACGTACGAGTGCGTCAC CGGCCGCT

GC ACC AC ACCT ACCGCCTG ACCGT A A ACC AG ACTTTTTCCGG AC AG ACCTC A AT A ACTCTGTTT AC

CAGAACAGGAGGTGAGCTTAGAAAACCCTTAGGGTATTAGGCCAAAGGCGCAGCTAC TGTGGGGT

TTATGAACAATTCAAGCAACTCTACGGGCTATTCTAATTCAGGTTTCTCTAGAAATG GACGGAATT

ATTACAGAGCAGCGCCTGCTAGAAAGACGCAGGGCAGCGGCCGAGCAACAGCGCATG AATCAAG

AGCTCCAAGACATGGTTAACTTGCACCAGTGCAAAAGGGGTATCTTTTGTCTGGTAA AGCAGGCCA

AAGTCACCTACGACAGTAATACCACCGGACACCGCCTTAGCTACAAGTTGCCAACCA AGCGTCAG

AAATTGGTGGTCATGGTGGGAGAAAAGCCCATTACCATAACTCAGCACTCGGTAGAA ACCGAAGG CTGCATTCACTCACCTTGTCAAGGACCTGAGGATCTCTGCACCCTTATTAAGACCCTGTG CGGTCTC

A A AG ATCTT ATTCCCTTTA ACT A AT A A A A A A A A AT A AT A A AGC ATC ACTT ACTT A A A ATC AGTT AG

CAAATTTCTGTCCAGTTTATTCAGCAGCACCTCCTTGCCCTCCTCCCAGCTCTGGTA TTGCAGCTTC

CTCCTGGCTGCAAACTTTCTCCACAATCTAAATGGAATGTCAGTTTCCTCCTGTTCC TGTCCATCCG

CACCCACTATCTTCATGTTGTTGCAGATGAAGCGCGCAAGACCGTCTGAAGATACCT TCAACCCCG

TGTATCCATATGACACGGAAACCGGTCCTCCAACTGTGCCTTTTCTTACTCCTCCCT TTGTATCCCC

CAATGGGTTTCAAGAGAGTCCCCCTGGGGTACTCTCTTTGCGCCTATCCGAACCTCT AGTTACCTCC

AATGGCATGCTTGCGCTCAAAATGGGCAACGGCCTCTCTCTGGACGAGGCCGGCAAC CTTACCTCC

CAAAATGTAACCACTGTGAGCCCACCTCTCAAAAAAACCAAGTCAAACATAAACCTG GAAATATC

TGCACCCCTCACAGTTACCTCAGAAGCCCTAACTGTGGCTGCCGCCGCACCTCTAAT GGTCGCGGG

CAACACACTCACCATGCAATCACAGGCCCCGCTAACCGTGCACGACTCCAAACTTAG CATTGCCAC

CCAAGGACCCCTCACAGTGTCAGAAGGAAAGCTAGCCCTGCAAACATCAGGCCCCCT CACCACCA

CCG AT AGC AGT ACCCTT ACT ATC ACTGCCTC ACCCCCTCT A ACT ACTGCC ACTGGT AGCTTGGGC AT

TGACTTGAAAGAGCCCATTTATACACAAAATGGAAAACTAGGACTAAAGTACGGGGC TCCTTTGC

ATGTAACAGACGACCTAAACACTTTGACCGT AGC AACTGGTCCAGGTGTGACT ATT AATAAT ACTT

CCTTGCAAACTAAAGTTACTGGAGCCTTGGGTTTTGATTCACAAGGCAATATGCAAC TTAATGTAG

CAGGAGGACTAAGGATTGATTCTCAAAACAGACGCCTTATACTTGATGTTAGTTATC CGTTTGATG

CTC A A A ACC A ACT A A ATCT A AG ACT AGG AC AGGGCCCTCTTTTT AT A A ACTC AGCCC AC A ACTTGG

AT ATT AACT AC A AC A A AGGCCTTT ACTTGTTT AC AGCTTC A A AC A ATTCC A A A A AGCTTG AGGTT A

ACCTAAGCACTGCCAAGGGGTTGATGTTTGACGCTACAGCCATAGCCATTAATGCAG GAGATGGG

CTTGAATTTGGTTCACCTAATGCACCAAACACAAATCCCCTCAAAACAAAAATTGGC CATGGCCTA

GAATTTGATTCAAACAAGGCTATGGTTCCTAAACTAGGAACTGGCCTTAGTTTTGAC AGCACAGGT

GCCATTACAGTAGGAAACAAAAATAATGATAAGCTAACTTTGTGGACCACACCAGCT CCATCTCCT

AACTGTAGACTAAATGCAGAGAAAGATGCTAAACTCACTTTGGTCTTAACAAAATGT GGCAGTCA

AATACTTGCTACAGTTTCAGTTTTGGCTGTTAAAGGCAGTTTGGCTCCAATATCTGG AACAGTTCA

AAGTGCTCATCTTATTATAAGATTTGACGAAAATGGAGTGCTACTAAACAATTCCTT CCTGGACCC

AGAATATTGGAACTTTAGAAATGGAGATCTTACTGAAGGCACAGCCTATACAAACGC TGTTGGATT

T ATGCCT A ACCT ATC AGCTT ATCC A A A ATCTC ACGGT A A A ACTGCC A A A AGT A AC ATTGTC AGTC A

AGTTT ACTT AA ACGG AG AC A A A ACT A A ACCTGT AAC ACT A ACC ATT AC ACT A A ACGGT AC AC AGG

AAACAGGAGACACAACTCCAAGTGCATACTCTATGTCATTTTCATGGGACTGGTCTG GCCACAACT

AC ATT A ATG A A AT ATTTGCC AC ATCCTCTT AC ACTTTTTC AT AC ATTGCCC A AG A AT A A AG A ATCGT

TTGTGTTATGTTTCAACGTGTTTATTTTTCAATTGCAGAAAATTTCGAATCATTTTT CATTCAGTAGT

AT AGCCCC ACC ACC AC AT AGCTT AT AC AG ATC ACCGT ACCTT A ATC A A ACTC AC AG A ACCCT AGT A

TTCAACCTGCCACCTCCCTCCCAACACACAGAGTACACAGTCCTTTCTCCCCGGCTG GCCTTAAAA

AGC ATC AT ATC ATGGGT AAC AG AC AT ATTCTT AGGTGTT AT ATTCC AC ACGGTTTCCTGTCGAGCC

AAACGCTCATCAGTGATATTAATAAACTCCCCGGGCAGCTCACTTAAGTTCATGTCG CTGTCCAGC

TGCTGAGCCACAGGCTGCTGTCCAACTTGCGGTTGCTTAACGGGCGGCGAAGGAGAA GTCCACGC

CTACATGGGGGTAGAGTCATAATCGTGCATCAGGATAGGGCGGTGGTGCTGCAGCAG CGCGCGAA

TAAACTGCTGCCGCCGCCGCTCCGTCCTGCAGGAATACAACATGGCAGTGGTCTCCT CAGCGATGA

TTCGCACCGCCCGCAGCATAAGGCGCCTTGTCCTCCGGGCACAGCAGCGCACCCTGA TCTCACTTA

AATCAGCACAGTAACTGCAGCACAGCACCACAATATTGTTCAAAATCCCACAGTGCA AGGCGCTG

TATCCAAAGCTCATGGCGGGGACCACAGAACCCACGTGGCCATCATACCACAAGCGC AGGTAGAT

TAAGTGGCGACCCCTCATAAACACGCTGGACATAAACATTACCTCTTTTGGCATGTT GTAATTCAC

C ACCTCCCGGT ACC AT ATA A ACCTCTG ATT A A AC AT GGCGCC ATCC ACC ACC ATCCT A A ACC AGCT

GGCCAAAACCTGCCCGCCGGCTATACACTGCAGGGAACCGGGACTGGAACAATGACA GTGGAGA

GCCCAGGACTCGTAACCATGGATCATCATGCTCGTCATGATATCAATGTTGGCACAA CACAGGCAC

ACGTGC AT AC ACTTCCTC AGG ATT AC A AGCTCCTCCCGCGTT AG A ACC AT ATCCC AGGG A AC A ACC

CATTCCTGAATCAGCGTAAATCCCACACTGCAGGGAAGACCTCGCACGTAACTCACG TTGTGCATT

GTCAAAGTGTTACATTCGGGCAGCAGCGGATGATCCTCCAGTATGGTAGCGCGGGTT TCTGTCTCA

AAAGGAGGTAGACGATCCCTACTGTACGGAGTGCGCCGAGACAACCGAGATCGTGTT GGTCGTAG

TGTCATGCCAAATGGAACGCCGGACGTAGTCATATTTCCTGAAGCAAAACCAGGTGC GGGCGTGA

C A A AC AG ATCTGCGTCTCCGGTCTCGCCGCTT AG ATCGCTCTGTGT AGT AGTTGT AGT AT ATCC ACT

CTCTCAAAGCATCCAGGCGCCCCCTGGCTTCGGGTTCTATGTAAACTCCTTCATGCG CCGCTGCCCT

GAT A AC ATCC ACC ACCGC AG A AT A AGCC AC ACCC AGCC A ACCT AC AC ATTCGTTCTGCG AGTC AC

ACACGGGAGGAGCGGGAAGAGCTGGAAGAACCATGTTTTTTTTTTTATTCCAAAAGA TTATCCAAA

ACCTCAAAATGAAGATCTATTAAGTGAACGCGCTCCCCTCCGGTGGCGTGGTCAAAC TCTACAGCC

AAAGAACAGATAATGGCATTTGTAAGATGTTGCACAATGGCTTCCAAAAGGCAAACG GCCCTCAC

GTCC A AGTGG ACGT A A AGGCT A A ACCCTTC AGGGTG A ATCTCCTCT AT A A AC ATTCC AGC ACCTTC

A ACC ATGCCC A A AT A ATTCTC ATCTCGCC ACCTTCTC A AT AT ATCTCT AAGC A A ATCCCG A AT ATT A AGTCCGGCCATTGTAAAAATCTGCTCCAGAGCGCCCTCCACCTTCAGCCTCAAGCAGCGA ATCATG

ATTGCAAAAATTCAGGTTCCTCACAGACCTGTATAAGATTCAAAAGCGGAACATTAA CAAAAATA

CCGCGATCCCGTAGGTCCCTTCGCAGGGCCAGCTGAACATAATCGTGCAGGTCTGCA CGGACCAG

CGCGGCCACTTCCCCGCCAGGAACCATGACAAAAGAACCCACACTGATTATGACACG CATACTCG

GAGCTATGCTAACCAGCGTAGCCCCGATGTAAGCTTGTTGCATGGGCGGCGATATAA AATGCAAG

GTGCTGCTCAAAAAATCAGGCAAAGCCTCGCGCAAAAAAGAAAGCACATCGTAGTCA TGCTCATG

CAGATAAAGGCAGGTAAGCTCCGGAACCACCACAGAAAAAGACACCATTTTTCTCTC AAACATGT

CTGCGGGTTTCTGCATAAACACAAAATAAAATAACAAAAAAACATTTAAACATTAGA AGCCTGTC

TTACAACAGGAAAAACAACCCTTATAAGCATAAGACGGACTACGGCCATGCCGGCGT GACCGTAA

AAAAACTGGTCACCGTGATTAAAAAGCACCACCGACAGCTCCTCGGTCATGTCCGGA GTCATAAT

GTAAGACTCGGTAAACACATCAGGTTGATTCACATCGGTCAGTGCTAAAAAGCGACC GAAATAGC

CCGGGGGAATACATACCCGCAGGCGTAGAGACAACATTACAGCCCCCATAGGAGGTA TAACAAAA

TTAATAGG AG AG AAAAAC AC AT AAAC ACCTGAAAAACCCTCCTGCCT AGGC AAAAT AGC ACCCTC

CCGCTCCAGAACAACATACAGCGCTTCCACAGCGGCAGCCATAACAGTCAGCCTTAC CAGTAAAA

AAGAAAACCTATTAAAAAAACACCACTCGACACGGCACCAGCTCAATCAGTCACAGT GTAAAAAA

GGGCCAAGTGCAGAGCGAGTATATATAGGACTAAAAAATGACGTAACGGTTAAAGTC CACAAAA

AACACCCAGAAAACCGCACGCGAACCTACGCCCAGAAACGAAAGCCAAAAAACCCAC AACTTCCT

C A A ATCGTC ACTTCCGTTTTCCC ACGTT ACGTC ACTTCCC ATTTT AAG A A A ACT AC A ATTCCC A AC A

CAT AC A AGTT ACTCCGCCCT A A A ACCT ACGTC ACCCGCCCCGTTCCC ACGCCCCGCGCC ACGTC AC

AAACTCCACCCCCTCATTATCATATTGGCTTCAATCCAAAATAAGGTATATTATTGA TGATGTTAAT

TAATTTAAATCCGCATGCGATATCGAGCTCTCCCGGGAATTCGGATCTGCGACGCGA GGCTGGATG

GCCTTCCCC ATT ATG ATTCTTCTCGCGTTT A AGGGC ACC A AT A ACTGCCTT AAA A A A ATT ACGCCCC

GCCCTGCCACTCATCGCAGTACTGTTGTAATTCATTAAGCATTCTGCCGACATGGAA GCCATCACA

AACGGCATGATGAACCTGAATCGCCAGCGGCATCAGCACCTTGTCGCCTTGCGTATA ATATTTGCC

CATGGTGAAAACGGGGGCGAAGAAGTTGTCCATATTGGCCACGTTTAAATCAAAACT GGTGAAAC

TCACCCAGGGATTGGCTGAGACGAAAAACATATTCTCAATAAACCCTTTAGGGAAAT AGGCCAGG

TTTTCACCGTAACACGCCACATCTTGCGAATATATGTGTAGAAACTGCCGGAAATCG TCGTGGTAT

TCACTCCAGAGCGATGAAAACGTTTCAGTTTGCTCATGGAAAACGGTGTAACAAGGG TGAACACT

ATCCCATATCACCAGCTCACCGTCTTTCATTGCCATACGGAATTCCGGATGAGCATT CATCAGGCG

GGCAAGAATGTGAATAAAGGCCGGATAAAACTTGTGCTTATTTTTCTTTACGGTCTT TAAAAAGGC

CGTAATATCCAGCTGAACGGTCTGGTTATAGGTACATTGAGCAACTGACTGAAATGC CTCAAAATG

TTCTTT ACG ATGCC ATTGGG AT AT ATC A ACGGTGGT AT ATCCAGTGATTTTTTTCTCC ATTTT AGCTT

CCTTAGCTCCTGAAAATCTCGATAACTCAAAAAATACGCCCGGTAGTGATCTTATTT CATTATGGT

GAAAGTTGGAACCTCTTACGTGCCGATCAACGTCTCATTTTCGCCAAAAGTTGGCCC AGGGCTTCC

CGGT ATC A AC AGGG AC ACC AGG ATTT ATTT ATTCTGCG A AGTG ATCTTCCGTC AC AGGT ATTT ATT

CGCGATAAGCTCATGGAGCGGCGTAACCGTCGCACAGGAAGGACAGAGAAAGCGCGG ATCTGGG

AAGTGACGGACAGAACGGTCAGGACCTGGATTGGGGAGGCGGTTGCCGCCGCTGCTG CTGACGGT

GTGACGTTCTCTGTTCCGGTCACACCACATACGTTCCGCCATTCCTATGCGATGCAC ATGCTGTATG

CCGGTATACCGCTGAAAGTTCTGCAAAGCCTGATGGGACATAAGTCCATCAGTTCAA CGGAAGTCT

ACACGAAGGTTTTTGCGCTGGATGTGGCTGCCCGGCACCGGGTGCAGTTTGCGATGC CGGAGTCTG

ATGCGGTTGCGATGCTGAAACAATTATCCTGAGAATAAATGCCTTGGCCTTTATATG GAAATGTGG

AACTGAGTGGATATGCTGTTTTTGTCTGTTAAACAGAGAAGCTGGCTGTTATCCACT GAGAAGCGA

ACG AAAC AGTCGGG AAA ATCTCCC ATT ATCGT AG AG ATCCGC ATT ATT A ATCTC AGG AGCCTGTGT

AGCGTTTATAGGAAGTAGTGTTCTGTCATGATGCCTGCAAGCGGTAACGAAAACGAT TTGAATATG

CCTTCAGGAACAATAGAAATCTTCGTGCGGTGTTACGTTGAAGTGGAGCGGATTATG TCAGCAATG

GACAGAACAACCTAATGAACACAGAACCATGATGTGGTCTGTCCTTTTACAGCCAGT AGTGCTCGC

CGCAGTCGAGCGACAGGGCGAAGCCCTCGAGTGAGCGAGGAAGCACCAGGGAACAGC ACTTATA

TATTCTGCTTACACACGATGCCTGAAAAAACTTCCCTTGGGGTTATCCACTTATCCA CGGGGATATT

TTT AT A ATT ATTTTTTTT AT AGTTTTT AG ATCTTCTTTTTT AG AGCGCCTTGT AGGCCTTT ATCC ATG

CTGGTTCTAGAGAAGGTGTTGTGACAAATTGCCCTTTCAGTGTGACAAATCACCCTC AAATGACAG

TCCTGTCTGTGACAAATTGCCCTTAACCCTGTGACAAATTGCCCTCAGAAGAAGCTG TTTTTTCACA

A AGTT ATCCCTGCTT ATTG ACTCTTTTTT ATTT AGTGTG AC A ATCT A A A A ACTTGTC AC ACTTC AC A

TGGATCTGTCATGGCGGAAACAGCGGTTATCAATCACAAGAAACGTAAAAATAGCCC GCGAATCG

TCCAGTCAAACGACCTCACTGAGGCGGCATATAGTCTCTCCCGGGATCAAAAACGTA TGCTGTATC

TGTTCGTTGACCAGATCAGAAAATCTGATGGCACCCTACAGGAACATGACGGTATCT GCGAGATCC

ATGTTGCTAAATATGCTGAAATATTCGGATTGACCTCTGCGGAAGCCAGTAAGGATA TACGGCAG

GCATTGAAGAGTTTCGCGGGGAAGGAAGTGGTTTTTTATCGCCCTGAAGAGGATGCC GGCGATGA

AAAAGGCTATGAATCTTTTCCTTGGTTTATCAAACGTGCGCACAGTCCATCCAGAGG GCTTTACAG

TGT AC AT ATC A ACCC AT ATCTC ATTCCCTTCTTT ATCGGGTT AC AG A ACCGGTTT ACGC AGTTTCGG CTTAGTGAAACAAAAGAAATCACCAATCCGTATGCCATGCGTTTATACGAATCCCTGTGT CAGTAT

CGTAAGCCGGATGGCTCAGGCATCGTCTCTCTGAAAATCGACTGGATCATAGAGCGT TACCAGCTG

CCTCAAAGTTACCAGCGTATGCCTGACTTCCGCCGCCGCTTCCTGCAGGTCTGTGTT AATGAGATC

AACAGCAGAACTCCAATGCGCCTCTCATACATTGAGAAAAAGAAAGGCCGCCAGACG ACTCATAT

CGTATTTTCCTTCCGCGATATCACTTCCATGACGACAGGATAGTCTGAGGGTTATCT GTCACAGATT

TGAGGGTGGTTCGTCACATTTGTTCTGACCTACTGAGGGTAATTTGTCACAGTTTTG CTGTTTCCTT

CAGCCTGCATGGATTTTCTCATACTTTTTGAACTGTAATTTTTAAGGAAGCCAAATT TGAGGGCAGT

TTGTCACAGTTGATTTCCTTCTCTTTCCCTTCGTCATGTGACCTGATATCGGGGGTT AGTTCGTCATC

ATTGATGAGGGTTGATTATCACAGTTTATTACTCTGAATTGGCTATCCGCGTGTGTA CCTCTACCTG

GAGTTTTTCCCACGGTGGATATTTCTTCTTGCGCTGAGCGTAAGAGCTATCTGACAG AACAGTTCTT

CTTTGCTTCCTCGCCAGTTCGCTCGCTATGCTCGGTTACACGGCTGCGGCGAGCGCT AGTGATAAT

AAGTGACTGAGGTATGTGCTCTTCTTATCTCCTTTTGTAGTGTTGCTCTTATTTTAA ACAACTTTGCG

_{GTTTTTTGATGACTTTGCGATTTTGTTGTTGCTTTGCAGTAAATTGCAAGATTTA ATAAAAAAACGC}

AAAGCAATGATTAAAGGATGTTCAGAATGAAACTCATGGAAACACTTAACCAGTGCA TAAACGCT

GGTCATGAAATGACGAAGGCTATCGCCATTGCACAGTTTAATGATGACAGCCCGGAA GCGAGGAA

AATAACCCGGCGCTGGAGAATAGGTGAAGCAGCGGATTTAGTTGGGGTTTCTTCTCA GGCTATCAG

AGATGCCGAGAAAGCAGGGCGACTACCGCACCCGGATATGGAAATTCGAGGACGGGT TGAGCAA

CGTGTTGGTTATACAATTGAACAAATTAATCATATGCGTGATGTGTTTGGTACGCGA TTGCGACGT

GCTGAAGACGTATTTCCACCGGTGATCGGGGTTGCTGCCCATAAAGGTGGCGTTTAC AAAACCTCA

GTTTCTGTTCATCTTGCTCAGGATCTGGCTCTGAAGGGGCTACGTGTTTTGCTCGTG GAAGGTAACG

ACCCCCAGGGAACAGCCTCAATGTATCACGGATGGGTACCAGATCTTCATATTCATG CAGAAGAC

ACTCTCCTGCCTTTCTATCTTGGGGAAAAGGACGATGTCACTTATGCAATAAAGCCC ACTTGCTGG

CCGGGGCTTGACATTATTCCTTCCTGTCTGGCTCTGCACCGTATTGAAACTGAGTTA ATGGGCAAA

TTTGATGAAGGTAAACTGCCCACCGATCCACACCTGATGCTCCGACTGGCCATTGAA ACTGTTGCT

CATGACTATGATGTCATAGTTATTGACAGCGCGCCTAACCTGGGTATCGGCACGATT AATGTCGTA

TGTGCTGCTGATGTGCTGATTGTTCCCACGCCTGCTGAGTTGTTTGACTACACCTCC GCACTGCAGT

TTTTCGATATGCTTCGTGATCTGCTCAAGAACGTTGATCTTAAAGGGTTCGAGCCTG ATGTACGTAT

TTTGCTTACCAAATACAGCAATAGTAATGGCTCTCAGTCCCCGTGGATGGAGGAGCA AATTCGGGA

TGCCTGGGGAAGCATGGTTCTAAAAAATGTTGTACGTGAAACGGATGAAGTTGGTAA AGGTCAGA

TCCGGATGAGAACTGTTTTTGAACAGGCCATTGATCAACGCTCTTCAACTGGTGCCT GGAGAAATG

CTCTTTCTATTTGGGAACCTGTCTGCAATGAAATTTTCGATCGTCTGATTAAACCAC GCTGGGAGAT

T AG AT A ATG A AGCGTGCGCCTGTT ATTCC A A A AC AT ACGCTC A AT ACTC A ACCGGTTG A AG AT ACT

TCGTTATCGACACCAGCTGCCCCGATGGTGGATTCGTTAATTGCGCGCGTAGGAGTA ATGGCTCGC

GGTAATGCCATTACTTTGCCTGTATGTGGTCGGGATGTGAAGTTTACTCTTGAAGTG CTCCGGGGT

GATAGTGTTGAGAAGACCTCTCGGGTATGGTCAGGTAATGAACGTGACCAGGAGCTG CTTACTGA

GGACGCACTGGATGATCTCATCCCTTCTTTTCTACTGACTGGTCAACAGACACCGGC GTTCGGTCG

AAGAGTATCTGGTGTCATAGAAATTGCCGATGGGAGTCGCCGTCGTAAAGCTGCTGC ACTTACCGA

AAGTGATTATCGTGTTCTGGTTGGCGAGCTGGATGATGAGCAGATGGCTGCATTATC CAGATTGGG

TAACGATTATCGCCCAACAAGTGCTTATGAACGTGGTCAGCGTTATGCAAGCCGATT GCAGAATGA

ATTTGCTGGAAATATTTCTGCGCTGGCTGATGCGGAAAATATTTCACGTAAGATTAT TACCCGCTG

TATCAACACCGCCAAATTGCCTAAATCAGTTGTTGCTCTTTTTTCTCACCCCGGTGA ACTATCTGCC

CGGTCAGGTGATGCACTTCAAAAAGCCTTTACAGATAAAGAGGAATTACTTAAGCAG CAGGCATC

TAACCTTCATGAGCAGAAAAAAGCTGGGGTGATATTTGAAGCTGAAGAAGTTATCAC TCTTTTAAC

TTCTGTGCTTAAAACGTCATCTGCATCAAGAACTAGTTTAAGCTCACGACATCAGTT TGCTCCTGG

AGCGACAGTATTGTATAAGGGCGATAAAATGGTGCTTAACCTGGACAGGTCTCGTGT TCCAACTGA

GTGTATAGAGAAAATTGAGGCCATTCTTAAGGAACTTGAAAAGCCAGCACCCTGATG CGACCACG

TTTT AGTCT ACGTTT ATCTGTCTTT ACTT AATGTCCTTTGTT AC AGGCC AG A A AGC AT A ACTGGCCT

GAATATTCTCTCTGGGCCCACTGTTCCACTTGTATCGTCGGTCTGATAATCAGACTG GGACCACGG

TCCCACTCGTATCGTCGGTCTGATTATTAGTCTGGGACCACGGTCCCACTCGTATCG TCGGTCTGAT

TATTAGTCTGGGACCACGGTCCCACTCGTATCGTCGGTCTGATAATCAGACTGGGAC CACGGTCCC

ACTCGTATCGTCGGTCTGATTATTAGTCTGGGACCATGGTCCCACTCGTATCGTCGG TCTGATTATT

AGTCTGGGACCACGGTCCCACTCGTATCGTCGGTCTGATTATTAGTCTGGAACCACG GTCCCACTC

GT ATCGTCGGTCTG ATT ATT AGTCTGGG ACC ACGGTCCC ACTCGT ATCGTCGGTCTG ATT ATT AGTC

TGGGACCACGATCCCACTCGTGTTGTCGGTCTGATTATCGGTCTGGGACCACGGTCC CACTTGTATT

GTCGATCAGACTATCAGCGTGAGACTACGATTCCATCAATGCCTGTCAAGGGCAAGT ATTGACATG

TCGTCGTAACCTGTAGAACGGAGTAACCTCGGTGTGCGGTTGTATGCCTGCTGTGGA TTGCTGCTG

TGTCCTGCTTATCCACAACATTTTGCGCACGGTTATGTGGACAAAATACCTGGTTAC CCAGGCCGT

GCCGGC ACGTT AACCGGGC AC ATTTCCCCG A A A AGTGCC ACCTG ACGTCT A AG A A ACC ATT ATT AT C ATG AC ATT AACCT AT A A A A AT AGGCGT ATC ACG AGGCCCTTTCGTCTTC A AG A ATTGG ATCCG A A TTCCCGGG AG AGCTCG AT ATCGC ATGCGG ATTT A A ATT A ATT A A

* C1D (SEQ ID NO: 85)

CATCATCAATAATATACCTTATTTTGGATTGAAGCCAATATGATAATGAGGGGGTGGAGT TTGTGA

CGTGGCGCGGGGCGTGGGAACGGGGCGGGTGACGTAGTAGTGTGGCGGAAGTGTGAT GTTGCAAG

TGTGGCGGAACACATGTAAGCGACGGATGTGGCAAAAGTGACGTTTTTGGTGTGCGC CGGTGTAC

ACAGGAAGTGACAATTTTCGCGCGGTTTTAGGCGGATGTTGTAGTAAATTTGGGCGT AACCGAGTA

AGATTTGGCCATTTTCGCGGGAAAACTGAATAAGAGGAAGTGAAATCTGAATAATTT TGTGTTACT

CATAGCGCGTAATATTTGTCTAGGGCCGCGGGGACTTTGACCGTTTACGTGGAGACT CGCCCAGGT

GTTTTTCTC AGGTGTTTTCCGCGTTCCGGGTC A A AGTTGGCGTTTT ATT ATT AT AGTC AGTCG A AGC

TTGGATCCGGTACCTCTAGAATTCTCGAGCGGCCGCTAGCGACATCGGATCTCCCGA TCCCCTATG

GTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGTATCTGCTCCC TGCTTGTGTG

TTGGAGGTCGCTGAGTAGTGCGCGAGCAAAATTTAAGCTACAACAAGGCAAGGCTTG ACCGACAA

TTGCATGAAGAATCTGCTTAGGGTTAGGCGTTTTGCGCTGCTTCGCGATGTACGGGC CAGATATAC

GCGTTG AC ATTG ATT ATTG ACT AGTT ATT AAT AGT A ATC A ATT ACGGGGTC ATT AGTTC AT AGCCC

ATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCC CAACGACCC

CCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTT CCATTGACG

TCAATGGGTGGACTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCA TATGCCAAG

TACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTA CATGACCTT

ATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGT GATGCGGTTT

TGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTC CACCCCATT

GACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGT AACAACTCC

GCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGA GCTCTCTG

GCT A ACT AG AG A ACCC ACTGCTT ACTGGCTT ATCGA A ATT AAT ACG ACTC ACT AT AGGG AG ACCC A

AGCTGGCT AGTT A AGCT ATC A AC A AGTTTGT AC A A A A A AGC AGGCTTT A A AGG A ACC A ATTC AGT

CGACTGGATCCGGTACCACCATGTTCCTGAACTGCTGCCCAGGTTGCTGTATGGAGC CTGAATTCA

CCATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGC TGGACGGC

GACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTAC GGCAAGCT

GACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGT GACCACCCT

GACCTGGGGCGTGCAGTGCTTCGCCCGCTACCCCGACCACATGAAGCAGCACGACTT CTTCAAGTC

CGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAA CTACAAGA

CCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGG GCATCGAC

TTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACGCCATCAGCGAC AACGTCTA

TATCACCGCCGACAAGCAGAAGAACGGCATCAAGGCCAACTTCAAGATCCGCCACAA CATCGAGG

ACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCC CCGTGCTG

CTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAG AAGCGCGA

TCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGA GCTGTACAA

GGTCGACTATCCGTACGACGTACCAGACTACGCATAACCGCGGCCGCACTCGAGATA TCTAGACC

CAGCTTTCTTGTACAAAGTGGTTGATCTAGAGGGCCCGCGGTTCGAAGGTAAGCCTA TCCCTAACC

CTCTCCTCGGTCTCGATTCTACGCGTACCGGTTAGTAATGAGTTTAAACGGGGGAGG CTAACTGAA

ACACGGAAGGAGACAATACCGGAAGGAACCCGCGCTATGACGGCAATAAAAAGACAG AATAAAA

CGCACGGGTGTTGGGTCGTTTGTTCATAAACGCGGGGTTCGGTCCCAGGGCTGGCAC TCTGTCGAT

ACCCCACCGAGACCCCATTGGGGCCAATACGCCCGCGTTTCTTCCTTTTCCCCACCC CACCCCCCA

AGTTCGGGTGAAGGCCCAGGGCTCGCAGCCAACGTCGGGGCGGCAGGCCCTGCCATA GCAGATCC

GATTCGACAGATCACTGAAATGTGTGGGCGTGGCTTAAGGGTGGGAAAGAATATATA AGGTGGGG

GTCTTATGTAGTTTTGTATCTGTTTTGCAGCAGCCGCCGCCGCCATGAGCACCAACT CGTTTGATGG

AAGCATTGTGAGCTCATATTTGACAACGCGCATGCCCCCATGGGCCGGGGTGCGTCA GAATGTGAT

GGGCTCCAGCATTGATGGTCGCCCCGTCCTGCCCGCAAACTCTACTACCTTGACCTA CGAGACCGT

GTCTGGAACGCCGTTGGAGACTGCAGCCTCCGCCGCCGCTTCAGCCGCTGCAGCCAC CGCCCGCGG

GATTGTGACTGACTTTGCTTTCCTGAGCCCGCTTGCAAGCAGTGCAGCTTCCCGTTC ATCCGCCCGC

GATGACAAGTTGACGGCTCTTTTGGCACAATTGGATTCTTTGACCCGGGAACTTAAT GTCGTTTCTC

AGCAGCTGTTGGATCTGCGCCAGCAGGTTTCTGCCCTGAAGGCTTCCTCCCCTCCCA ATGCGGTTT

AAAACATAAATAAAAAACCAGACTCTGTTTGGATTTGGATCAAGCAAGTGTCTTGCT GTCTTTATT

TAGGGGTTTTGCGCGCGCGGTAGGCCCGGGACCAGCGGTCTCGGTCGTTGAGGGTCC TGTGTATTT

TTTCCAGGACGTGGTAAAGGTGACTCTGGATGTTCAGATACATGGGCATAAGCCCGT CTCTGGGGT

GGAGGTAGCACCACTGCAGAGCTTCATGCTGCGGGGTGGTGTTGTAGATGATCCAGT CGTAGCAG GAGCGCTGGGCGTGGTGCCTAAAAATGTCTTTCAGTAGCAAGCTGATTGCCAGGGGCAGG CCCTT

GGTGTAAGTGTTTACAAAGCGGTTAAGCTGGGATGGGTGCATACGTGGGGATATGAG ATGCATCT

TGGACTGTATTTTTAGGTTGGCTATGTTCCCAGCCATATCCCTCCGGGGATTCATGT TGTGCAGAAC

CACCAGCACAGTGTATCCGGTGCACTTGGGAAATTTGTCATGTAGCTTAGAAGGAAA TGCGTGGA

AGAACTTGGAGACGCCCTTGTGACCTCCAAGATTTTCCATGCATTCGTCCATAATGA TGGCAATGG

GCCCACGGGCGGCGGCCTGGGCGAAGATATTTCTGGGATCACTAACGTCATAGTTGT GTTCCAGGA

TGAGATCGTCATAGGCCATTTTTACAAAGCGCGGGCGGAGGGTGCCAGACTGCGGTA TAATGGTT

CCATCCGGCCCAGGGGCGTAGTTACCCTCACAGATTTGCATTTCCCACGCTTTGAGT TCAGATGGG

GGGATCATGTCTACCTGCGGGGCGATGAAGAAAACGGTTTCCGGGGTAGGGGAGATC AGCTGGGA

AGAAAGCAGGTTCCTGAGCAGCTGCGACTTACCGCAGCCGGTGGGCCCGTAAATCAC ACCTATTA

CCGGCTGCAACTGGTAGTTAAGAGAGCTGCAGCTGCCGTCATCCCTGAGCAGGGGGG CCACTTCG

TTAAGCATGTCCCTGACTCGCATGTTTTCCCTGACCAAATCCGCCAGAAGGCGCTCG CCGCCCAGC

GATAGCAGTTCTTGCAAGGAAGCAAAGTTTTTCAACGGTTTGAGACCGTCCGCCGTA GGCATGCTT

TTGAGCGTTTGACCAAGCAGTTCCAGGCGGTCCCACAGCTCGGTCACCTGCTCTACG GCATCTCGA

TCCAGCATATCTCCTCGTTTCGCGGGTTGGGGCGGCTTTCGCTGTACGGCAGTAGTC GGTGCTCGTC

CAGACGGGCCAGGGTCATGTCTTTCCACGGGCGCAGGGTCCTCGTCAGCGTAGTCTG GGTCACGGT

GAAGGGGTGCGCTCCGGGCTGCGCGCTGGCCAGGGTGCGCTTGAGGCTGGTCCTGCT GGTGCTGA

AGCGCTGCCGGTCTTCGCCCTGCGCGTCGGCCAGGTAGCATTTGACCATGGTGTCAT AGTCCAGCC

CCTCCGCGGCGTGGCCCTTGGCGCGCAGCTTGCCCTTGGAGGAGGCGCCGCACGAGG GGCAGTGC

AGACTTTTGAGGGCGTAGAGCTTGGGCGCGAGAAATACCGATTCCGGGGAGTAGGCA TCCGCGCC

GCAGGCCCCGCAGACGGTCTCGCATTCCACGAGCCAGGTGAGCTCTGGCCGTTCGGG GTCAAAAA

CCAGGTTTCCCCCATGCTTTTTGATGCGTTTCTTACCTCTGGTTTCCATGAGCCGGT GTCCACGCTC

GGTGACGAAAAGGCTGTCCGTGTCCCCGTATACAGACTTGAGAGGCCTGTCCTCGAG CGGTGTTCC

GCGGTCCTCCTCGTATAGAAACTCGGACCACTCTGAGACAAAGGCTCGCGTCCAGGC CAGCACGA

AGGAGGCTAAGTGGGAGGGGTAGCGGTCGTTGTCCACTAGGGGGTCCACTCGCTCCA GGGTGTGA

AGACACATGTCGCCCTCTTCGGCATCAAGGAAGGTGATTGGTTTGTAGGTGTAGGCC ACGTGACCG

GGTGTTCCTGAAGGGGGGCTATAAAAGGGGGTGGGGGCGCGTTCGTCCTCACTCTCT TCCGCATCG

CTGTCTGCGAGGGCCAGCTGTTGGGGTGAGTACTCCCTCTGAAAAGCGGGCATGACT TCTGCGCTA

AGATTGTCAGTTTCCAAAAACGAGGAGGATTTGATATTCACCTGGCCCGCGGTGATG CCTTTGAGG

GTGGCCGCATCCATCTGGTCAGAAAAGACAATCTTTTTGTTGTCAAGCTTGGTGGCA AACGACCCG

TAGAGGGCGTTGGACAGCAACTTGGCGATGGAGCGCAGGGTTTGGTTTTTGTCGCGA TCGGCGCG

CTCCTTGGCCGCGATGTTTAGCTGCACGTATTCGCGCGCAACGCACCGCCATTCGGG AAAGACGGT

GGTGCGCTCGTCGGGCACCAGGTGCACGCGCCAACCGCGGTTGTGCAGGGTGACAAG GTCAACGC

TGGTGGCTACCTCTCCGCGTAGGCGCTCGTTGGTCCAGCAGAGGCGGCCGCCCTTGC GCGAGCAGA

ATGGCGGTAGGGGGTCTAGCTGCGTCTCGTCCGGGGGGTCTGCGTCCACGGTAAAGA CCCCGGGC

AGCAGGCGCGCGTCGAAGTAGTCTATCTTGCATCCTTGCAAGTCTAGCGCCTGCTGC CATGCGCGG

GCGGCAAGCGCGCGCTCGTATGGGTTGAGTGGGGGACCCCATGGCATGGGGTGGGTG AGCGCGGA

GGCGTACATGCCGCAAATGTCGTAAACGTAGAGGGGCTCTCTGAGTATTCCAAGATA TGTAGGGT

AGCATCTTCCACCGCGGATGCTGGCGCGCACGTAATCGTATAGTTCGTGCGAGGGAG CGAGGAGG

TCGGGACCGAGGTTGCTACGGGCGGGCTGCTCTGCTCGGAAGACTATCTGCCTGAAG ATGGCATGT

GAGTTGGATGATATGGTTGGACGCTGGAAGACGTTGAAGCTGGCGTCTGTGAGACCT ACCGCGTC

ACGCACGAAGGAGGCGTAGGAGTCGCGCAGCTTGTTGACCAGCTCGGCGGTGACCTG CACGTCTA

GGGCGCAGTAGTCCAGGGTTTCCTTGATGATGTCATACTTATCCTGTCCCTTTTTTT TCCACAGCTC

GCGGTTGAGGACAAACTCTTCGCGGTCTTTCCAGTACTCTTGGATCGGAAACCCGTC GGCCTCCGA

ACGGTAAGAGCCTAGCATGTAGAACTGGTTGACGGCCTGGTAGGCGCAGCATCCCTT TTCTACGGG

TAGCGCGTATGCCTGCGCGGCCTTCCGGAGCGAGGTGTGGGTGAGCGCAAAGGTGTC CCTGACCA

TGACCAGCATGAAGGGCACGAGCTGCTTCCCAAAGGCCCCCATCCAAGTATAGGTCT CTACATCGT

AGGTGACAAAGAGACGCTCGGTGCGAGGATGCGAGCCGATCGGGAAGAACTGGATCT CCCGCCAC

CAATTGGAGGAGTGGCTATTGATGTGGTGAAAGTAGAAGTCCCTGCGACGGGCCGAA CACTCGTG

CTGGCTTTTGTAAAAACGTGCGCAGTACTGGCAGCGGTGCACGGGCTGTACATCCTG CACGAGGTT

GACCTGACGACCGCGCACAAGGAAGCAGAGTGGGAATTTGAGCCCCTCGCCTGGCGG GTTTGGCT

GGTGGTCTTCTACTTCGGCTGCTTGTCCTTGACCGTCTGGCTGCTCGAGGGGAGTTA CGGTGGATC

GGACCACCACGCCGCGCGAGCCCAAAGTCCAGATGTCCGCGCGCGGCGGTCGGAGCT TGATGACA

ACATCGCGCAGATGGGAGCTGTCCATGGTCTGGAGCTCCCGCGGCGTCAGGTCAGGC GGGAGCTC

CTGCAGGTTTACCTCGCATAGACGGGTCAGGGCGCGGGCTAGATCCAGGTGATACCT AATTTCCAG

GGGCTGGTTGGTGGCGGCGTCGATGGCTTGCAAGAGGCCGCATCCCCGCGGCGCGAC TACGGTAC

CGCGCGGCGGGCGGTGGGCCGCGGGGGTGTCCTTGGATGATGCATCTAAAAGCGGTG ACGCGGGC

GAGCCCCCGGAGGTAGGGGGGGCTCCGGACCCGCCGGGAGAGGGGGCAGGGGCACGT CGGCGCC

GCGCGCGGGCAGGAGCTGGTGCTGCGCGCGTAGGTTGCTGGCGAACGCGACGACGCG GCGGTTGA TCTCCTGAATCTGGCGCCTCTGCGTGAAGACGACGGGCCCGGTGAGCTTGAACCTGAAAG AGAGT

TCGACAGAATCAATTTCGGTGTCGTTGACGGCGGCCTGGCGCAAAATCTCCTGCACG TCTCCTGAG

TTGTCTTGATAGGCGATCTCGGCCATGAACTGCTCGATCTCTTCCTCCTGGAGATCT CCGCGTCCGG

CTCGCTCCACGGTGGCGGCGAGGTCGTTGGAAATGCGGGCCATGAGCTGCGAGAAGG CGTTGAGG

CCTCCCTCGTTCCAGACGCGGCTGTAGACCACGCCCCCTTCGGCATCGCGGGCGCGC ATGACCACC

TGCGCGAGATTGAGCTCCACGTGCCGGGCGAAGACGGCGTAGTTTCGCAGGCGCTGA AAGAGGTA

GTTGAGGGTGGTGGCGGTGTGTTCTGCCACGAAGAAGTACATAACCCAGCGTCGCAA CGTGGATT

CGTTGATATCCCCCAAGGCCTCAAGGCGCTCCATGGCCTCGTAGAAGTCCACGGCGA AGTTGAAA

AACTGGGAGTTGCGCGCCGACACGGTTAACTCCTCCTCCAGAAGACGGATGAGCTCG GCGACAGT

GTCGCGCACCTCGCGCTCAAAGGCTACAGGGGCCTCTTCTTCTTCTTCAATCTCCTC TTCCATAAGG

GCCTCCCCTTCTTCTTCTTCTGGCGGCGGTGGGGGAGGGGGGACACGGCGGCGACGA CGGCGCAC

CGGGAGGCGGTCGACAAAGCGCTCGATCATCTCCCCGCGGCGACGGCGCATGGTCTC GGTGACGG

CGCGGCCGTTCTCGCGGGGGCGCAGTTGGAAGACGCCGCCCGTCATGTCCCGGTTAT GGGTTGGCG

GGGGGCTGCCATGCGGCAGGGATACGGCGCTAACGATGCATCTCAACAATTGTTGTG TAGGTACT

CCGCCGCCGAGGGACCTGAGCGAGTCCGCATCGACCGGATCGGAAAACCTCTCGAGA AAGGCGTC

TAACCAGTCACAGTCGCAAGGTAGGCTGAGCACCGTGGCGGGCGGCAGCGGGCGGCG GTCGGGGT

TGTTTCTGGCGGAGGTGCTGCTGATGATGTAATTAAAGTAGGCGGTCTTGAGACGGC GGATGGTCG

ACAGAAGCACCATGTCCTTGGGTCCGGCCTGCTGAATGCGCAGGCGGTCGGCCATGC CCCAGGCTT

CGTTTTGACATCGGCGCAGGTCTTTGTAGTAGTCTTGCATGAGCCTTTCTACCGGCA CTTCTTCTTC

TCCTTCCTCTTGTCCTGCATCTCTTGCATCTATCGCTGCGGCGGCGGCGGAGTTTGG CCGTAGGTGG

CGCCCTCTTCCTCCCATGCGTGTGACCCCGAAGCCCCTCATCGGCTGAAGCAGGGCT AGGTCGGCG

ACAACGCGCTCGGCTAATATGGCCTGCTGCACCTGCGTGAGGGTAGACTGGAAGTCA TCCATGTCC

ACAAAGCGGTGGTATGCGCCCGTGTTGATGGTGTAAGTGCAGTTGGCCATAACGGAC CAGTTAAC

GGTCTGGTGACCCGGCTGCGAGAGCTCGGTGTACCTGAGACGCGAGTAAGCCCTCGA GTCAAATA

CGTAGTCGTTGCAAGTCCGCACCAGGTACTGGTATCCCACCAAAAAGTGCGGCGGCG GCTGGCGG

TAGAGGGGCCAGCGTAGGGTGGCCGGGGCTCCGGGGGCGAGATCTTCCAACATAAGG CGATGATA

TCCGTAGATGTACCTGGACATCCAGGTGATGCCGGCGGCGGTGGTGGAGGCGCGCGG AAAGTCGC

GGACGCGGTTCCAGATGTTGCGCAGCGGCAAAAAGTGCTCCATGGTCGGGACGCTCT GGCCGGTC

AGGCGCGCGCAATCGTTGACGCTCTAGACCGTGCAAAAGGAGAGCCTGTAAGCGGGC ACTCTTCC

GTGGTCTGGTGGATAAATTCGCAAGGGTATCATGGCGGACGACCGGGGTTCGAGCCC CGTATCCG

GCCGTCCGCCGTGATCCATGCGGTTACCGCCCGCGTGTCGAACCCAGGTGTGCGACG TCAGACAAC

GGGGGAGTGCTCCTTTTGGCTTCCTTCCAGGCGCGGCGGCTGCTGCGCTAGCTTTTT TGGCCACTGG

CCGCGCGCAGCGTAAGCGGTTAGGCTGGAAAGCGAAAGCATTAAGTGGCTCGCTCCC TGTAGCCG

GAGGGTTATTTTCCAAGGGTTGAGTCGCGGGACCCCCGGTTCGAGTCTCGGACCGGC CGGACTGCG

GCGAACGGGGGTTTGCCTCCCCGTCATGCAAGACCCCGCTTGCAAATTCCTCCGGAA ACAGGGAC

GAGCCCCTTTTTTGCTTTTCCCAGATGCATCCGGTGCTGCGGCAGATGCGCCCCCCT CCTCAGCAGC

GGCAAGAGCAAGAGCAGCGGCAGACATGCAGGGCACCCTCCCCTCCTCCTACCGCGT CAGGAGGG

GCGACATCCGCGGTTGACGCGGCAGCAGATGGTGATTACGAACCCCCGCGGCGCCGG GCCCGGCA

CTACCTGGACTTGGAGGAGGGCGAGGGCCTGGCGCGGCTAGGAGCGCCCTCTCCTGA GCGGCACC

CAAGGGTGCAGCTGAAGCGTGATACGCGTGAGGCGTACGTGCCGCGGCAGAACCTGT TTCGCGAC

CGCGAGGGAGAGGAGCCCGAGGAGATGCGGGATCGAAAGTTCCACGCAGGGCGCGAG CTGCGGC

ATGGCCTGAATCGCGAGCGGTTGCTGCGCGAGGAGGACTTTGAGCCCGACGCGCGAA CCGGGATT

AGTCCCGCGCGCGCACACGTGGCGGCCGCCGACCTGGTAACCGCATACGAGCAGACG GTGAACCA

GGAGATTAACTTTCAAAAAAGCTTTAACAACCACGTGCGTACGCTTGTGGCGCGCGA GGAGGTGG

CTATAGGACTGATGCATCTGTGGGACTTTGTAAGCGCGCTGGAGCAAAACCCAAATA GCAAGCCG

CTCATGGCGCAGCTGTTCCTTATAGTGCAGCACAGCAGGGACAACGAGGCATTCAGG GATGCGCT

GCTAAACATAGTAGAGCCCGAGGGCCGCTGGCTGCTCGATTTGATAAACATCCTGCA GAGCATAG

TGGTGCAGGAGCGCAGCTTGAGCCTGGCTGACAAGGTGGCCGCCATCAACTATTCCA TGCTTAGCC

TGGGCAAGTTTTACGCCCGCAAGATATACCATACCCCTTACGTTCCCATAGACAAGG AGGTAAAG

ATCGAGGGGTTCTACATGCGCATGGCGCTGAAGGTGCTTACCTTGAGCGACGACCTG GGCGTTTAT

CGCAACGAGCGCATCCACAAGGCCGTGAGCGTGAGCCGGCGGCGCGAGCTCAGCGAC CGCGAGCT

GATGCACAGCCTGCAAAGGGCCCTGGCTGGCACGGGCAGCGGCGATAGAGAGGCCGA GTCCTACT

TTGACGCGGGCGCTGACCTGCGCTGGGCCCCAAGCCGACGCGCCCTGGAGGCAGCTG GGGCCGGA

CCTGGGCTGGCGGTGGCACCCGCGCGCGCTGGCAACGTCGGCGGCGTGGAGGAATAT GACGAGGA

CGATGAGTACGAGCCAGAGGACGGCGAGTACTAAGCGGTGATGTTTCTGATCAGATG ATGCAAGA

CGCAACGGACCCGGCGGTGCGGGCGGCGCTGCAGAGCCAGCCGTCCGGCCTTAACTC CACGGACG

ACTGGCGCCAGGTCATGGACCGCATCATGTCGCTGACTGCGCGCAATCCTGACGCGT TCCGGCAGC

AGCCGCAGGCCAACCGGCTCTCCGCAATTCTGGAAGCGGTGGTCCCGGCGCGCGCAA ACCCCACG

CACGAGAAGGTGCTGGCGATCGTAAACGCGCTGGCCGAAAACAGGGCCATCCGGCCC GACGAGG CCGGCCTGGTCTACGACGCGCTGCTTCAGCGCGTGGCTCGTTACAACAGCGGCAACGTGC AGACC

AACCTGGACCGGCTGGTGGGGGATGTGCGCGAGGCCGTGGCGCAGCGTGAGCGCGCG CAGCAGC

AGGGCAACCTGGGCTCCATGGTTGCACTAAACGCCTTCCTGAGTACACAGCCCGCCA ACGTGCCGC

GGGGACAGGAGGACTACACCAACTTTGTGAGCGCACTGCGGCTAATGGTGACTGAGA CACCGCAA

AGTGAGGTGTACCAGTCTGGGCCAGACTATTTTTTCCAGACCAGTAGACAAGGCCTG CAGACCGTA

AACCTGAGCCAGGCTTTCAAAAACTTGCAGGGGCTGTGGGGGGTGCGGGCTCCCACA GGCGACCG

CGCGACCGTGTCTAGCTTGCTGACGCCCAACTCGCGCCTGTTGCTGCTGCTAATAGC GCCCTTCAC

GGACAGTGGCAGCGTGTCCCGGGACACATACCTAGGTCACTTGCTGACACTGTACCG CGAGGCCA

TAGGTCAGGCGCATGTGGACGAGCATACTTTCCAGGAGATTACAAGTGTCAGCCGCG CGCTGGGG

CAGGAGGACACGGGCAGCCTGGAGGCAACCCTAAACTACCTGCTGACCAACCGGCGG CAGAAGA

TCCCCTCGTTGCACAGTTTAAACAGCGAGGAGGAGCGCATTTTGCGCTACGTGCAGC AGAGCGTG

AGCCTTAACCTGATGCGCGACGGGGTAACGCCCAGCGTGGCGCTGGACATGACCGCG CGCAACAT

GGAACCGGGCATGTATGCCTCAAACCGGCCGTTTATCAACCGCCTAATGGACTACTT GCATCGCGC

GGCCGCCGTGAACCCCGAGTATTTCACCAATGCCATCTTGAACCCGCACTGGCTACC GCCCCCTGG

TTTCTACACCGGGGGATTCGAGGTGCCCGAGGGTAACGATGGATTCCTCTGGGACGA CATAGACG

ACAGCGTGTTTTCCCCGCAACCGCAGACCCTGCTAGAGTTGCAACAGCGCGAGCAGG CAGAGGCG

GCGCTGCGAAAGGAAAGCTTCCGCAGGCCAAGCAGCTTGTCCGATCTAGGCGCTGCG GCCCCGCG

GTC AG ATGCT AGT AGCCC ATTTCC A AGCTTG AT AGGGTCTCTT ACC AGC ACTCGC ACC ACCCGCCC

GCGCCTGCTGGGCGAGGAGGAGTACCTAAACAACTCGCTGCTGCAGCCGCAGCGCGA AAAAAACC

TGCCTCCGGCATTTCCCAACAACGGGATAGAGAGCCTAGTGGACAAGATGAGTAGAT GGAAGACG

TACGCGCAGGAGCACAGGGACGTGCCAGGCCCGCGCCCGCCCACCCGTCGTCAAAGG CACGACCG

TCAGCGGGGTCTGGTGTGGGAGGACGATGACTCGGCAGACGACAGCAGCGTCCTGGA TTTGGGAG

GGAGTGGCAACCCGTTTGCGCACCTTCGCCCCAGGCTGGGGAGAATGTTTTAAAAAA AAAAAAAG

CATGATGCAAAATAAAAAACTCACCAAGGCCATGGCACCGAGCGTTGGTTTTCTTGT ATTCCCCTT

AGTATGCGGCGCGCGGCGATGTATGAGGAAGGTCCTCCTCCCTCCTACGAGAGTGTG GTGAGCGC

GGCGCCAGTGGCGGCGGCGCTGGGTTCTCCCTTCGATGCTCCCCTGGACCCGCCGTT TGTGCCTCC

GCGGTACCTGCGGCCTACCGGGGGGAGAAACAGCATCCGTTACTCTGAGTTGGCACC CCTATTCGA

CACCACCCGTGTGTACCTGGTGGACAACAAGTCAACGGATGTGGCATCCCTGAACTA CCAGAACG

ACCACAGCAACTTTCTGACCACGGTCATTCAAAACAATGACTACAGCCCGGGGGAGG CAAGCACA

CAGACCATCAATCTTGACGACCGGTCGCACTGGGGCGGCGACCTGAAAACCATCCTG CATACCAA

CATGCCAAATGTGAACGAGTTCATGTTTACCAATAAGTTTAAGGCGCGGGTGATGGT GTCGCGCTT

GCCTACTAAGGACAATCAGGTGGAGCTGAAATACGAGTGGGTGGAGTTCACGCTGCC CGAGGGCA

ACTACTCCGAGACCATGACCATAGACCTTATGAACAACGCGATCGTGGAGCACTACT TGAAAGTG

GGCAGACAGAACGGGGTTCTGGAAAGCGACATCGGGGTAAAGTTTGACACCCGCAAC TTCAGACT

GGGGTTTGACCCCGTCACTGGTCTTGTCATGCCTGGGGTATATACAAACGAAGCCTT CCATCCAGA

CATCATTTTGCTGCCAGGATGCGGGGTGGACTTCACCCACAGCCGCCTGAGCAACTT GTTGGGCAT

CCGCAAGCGGCAACCCTTCCAGGAGGGCTTTAGGATCACCTACGATGATCTGGAGGG TGGTAACA

TTCCCGCACTGTTGGATGTGGACGCCTACCAGGCGAGCTTGAAAGATGACACCGAAC AGGGCGGG

GGTGGCGCAGGCGGCAGCAACAGCAGTGGCAGCGGCGCGGAAGAGAACTCCAACGCG GCAGCCG

CGGCAATGCAGCCGGTGGAGGACATGAACGATCATGCCATTCGCGGCGACACCTTTG CCACACGG

GCTGAGGAGAAGCGCGCTGAGGCCGAAGCAGCGGCCGAAGCTGCCGCCCCCGCTGCG CAACCCG

AGGTCGAGAAGCCTCAGAAGAAACCGGTGATCAAACCCCTGACAGAGGACAGCAAGA AACGCAG

TTACAACCTAATAAGCAATGACAGCACCTTCACCCAGTACCGCAGCTGGTACCTTGC ATACAACTA

CGGCGACCCTCAGACCGGAATCCGCTCATGGACCCTGCTTTGCACTCCTGACGTAAC CTGCGGCTC

GGAGCAGGTCTACTGGTCGTTGCCAGACATGATGCAAGACCCCGTGACCTTCCGCTC CACGCGCCA

GATCAGCAACTTTCCGGTGGTGGGCGCCGAGCTGTTGCCCGTGCACTCCAAGAGCTT CTACAACGA

CCAGGCCGTCTACTCCCAACTCATCCGCCAGTTTACCTCTCTGACCCACGTGTTCAA TCGCTTTCCC

GAGAACCAGATTTTGGCGCGCCCGCCAGCCCCCACCATCACCACCGTCAGTGAAAAC GTTCCTGCT

CTCACAGATCACGGGACGCTACCGCTGCGCAACAGCATCGGAGGAGTCCAGCGAGTG ACCATTAC

TGACGCCAGACGCCGCACCTGCCCCTACGTTTACAAGGCCCTGGGCATAGTCTCGCC GCGCGTCCT

ATCGAGCCGCACTTTTTGAGCAAGCATGTCCATCCTTATATCGCCCAGCAATAACAC AGGCTGGGG

CCTGCGCTTCCCAAGCAAGATGTTTGGCGGGGCCAAGAAGCGCTCCGACCAACACCC AGTGCGCG

TGCGCGGGCACTACCGCGCGCCCTGGGGCGCGCACAAACGCGGCCGCACTGGGCGCA CCACCGTC

GATGACGCCATCGACGCGGTGGTGGAGGAGGCGCGCAACTACACGCCCACGCCGCCA CCAGTGTC

CACAGTGGACGCGGCCATTCAGACCGTGGTGCGCGGAGCCCGGCGCT ATGCT AAAATGAAGAGAC

GGCGGAGGCGCGTAGCACGTCGCCACCGCCGCCGACCCGGCACTGCCGCCCAACGCG CGGCGGCG

GCCCTGCTTAACCGCGCACGTCGCACCGGCCGACGGGCGGCCATGCGGGCCGCTCGA AGGCTGGC

CGCGGGTATTGTCACTGTGCCCCCCAGGTCCAGGCGACGAGCGGCCGCCGCAGCAGC CGCGGCCA

TTAGTGCTATGACTCAGGGTCGCAGGGGCAACGTGTATTGGGTGCGCGACTCGGTTA GCGGCCTGC GCGTGCCCGTGCGCACCCGCCCCCCGCGCAACTAGATTGCAAGAAAAAACTACTTAGACT CGTACT

GTTGTATGTATCCAGCGGCGGCGGCGCGCAACGAAGCTATGTCCAAGCGCAAAATCA AAGAAGAG

ATGCTCCAGGTCATCGCGCCGGAGATCTATGGCCCCCCGAAGAAGGAAGAGCAGGAT TACAAGCC

CCGAAAGCTAAAGCGGGTCAAAAAGAAAAAGAAAGATGATGATGATGAACTTGACGA CGAGGTG

GAACTGCTGCACGCTACCGCGCCCAGGCGACGGGTACAGTGGAAAGGTCGACGCGTA AAACGTGT

TTTGCGACCCGGCACCACCGTAGTCTTTACGCCCGGTGAGCGCTCCACCCGCACCTA CAAGCGCGT

GTATGATGAGGTGTACGGCGACGAGGACCTGCTTGAGCAGGCCAACGAGCGCCTCGG GGAGTTTG

CCTACGGAAAGCGGCATAAGGACATGCTGGCGTTGCCGCTGGACGAGGGCAACCCAA CACCTAGC

CTAAAGCCCGTAACACTGCAGCAGGTGCTGCCCGCGCTTGCACCGTCCGAAGAAAAG CGCGGCCT

AAAGCGCGAGTCTGGTGACTTGGCACCCACCGTGCAGCTGATGGTACCCAAGCGCCA GCGACTGG

AAGATGTCTTGGAAAAAATGACCGTGGAACCTGGGCTGGAGCCCGAGGTCCGCGTGC GGCCAATC

AAGCAGGTGGCGCCGGGACTGGGCGTGCAGACCGTGGACGTTCAGATACCCACTACC AGTAGCAC

CAGTATTGCCACCGCCACAGAGGGCATGGAGACACAAACGTCCCCGGTTGCCTCAGC GGTGGCGG

ATGCCGCGGTGCAGGCGGTCGCTGCGGCCGCGTCCAAGACCTCTACGGAGGTGCAAA CGGACCCG

TGGATGTTTCGCGTTTCAGCCCCCCGGCGCCCGCGCCGTTCGAGGAAGTACGGCGCC GCCAGCGCG

CT ACTGCCCG A AT ATGCCCT AC ATCCTTCC ATTGCGCCT ACCCCCGGCT ATCGTGGCT AC ACCT ACC

GCCCCAGAAGACGAGCAACTACCCGACGCCGAACCACCACTGGAACCCGCCGCCGCC GTCGCCGT

CGCCAGCCCGTGCTGGCCCCGATTTCCGTGCGCAGGGTGGCTCGCGAAGGAGGCAGG ACCCTGGT

GCTGCCAACAGCGCGCTACCACCCCAGCATCGTTTAAAAGCCGGTCTTTGTGGTTCT TGCAGATAT

GGCCCTCACCTGCCGCCTCCGTTTCCCGGTGCCGGGATTCCGAGGAAGAATGCACCG TAGGAGGG

GCATGGCCGGCCACGGCCTGACGGGCGGCATGCGTCGTGCGCACCACCGGCGGCGGC GCGCGTCG

CACCGTCGCATGCGCGGCGGTATCCTGCCCCTCCTTATTCCACTGATCGCCGCGGCG ATTGGCGCC

GTGCCCGGAATTGCATCCGTGGCCTTGCAGGCGCAGAGACACTGATTAAAAACAAGT TGCATGTG

GAAAAATCAAAATAAAAAGTCTGGACTCTCACGCTCGCTTGGTCCTGTAACTATTTT GTAGAATGG

AAGACATCAACTTTGCGTCTCTGGCCCCGCGACACGGCTCGCGCCCGTTCATGGGAA ACTGGCAAG

ATATCGGCACCAGCAATATGAGCGGTGGCGCCTTCAGCTGGGGCTCGCTGTGGAGCG GCATTAAA

AATTTCGGTTCCACCGTTAAGAACTATGGCAGCAAGGCCTGGAACAGCAGCACAGGC CAGATGCT

GAGGGATAAGTTGAAAGAGCAAAATTTCCAACAAAAGGTGGTAGATGGCCTGGCCTC TGGCATTA

GCGGGGTGGTGGACCTGGCCAACCAGGCAGTGCAAAATAAGATTAACAGTAAGCTTG ATCCCCGC

CCTCCCGTAGAGGAGCCTCCACCGGCCGTGGAGACAGTGTCTCCAGAGGGGCGTGGC GAAAAGCG

TCCGCGCCCCGACAGGGAAGAAACTCTGGTGACGCAAATAGACGAGCCTCCCTCGTA CGAGGAGG

CACTAAAGCAAGGCCTGCCCACCACCCGTCCCATCGCGCCCATGGCTACCGGAGTGC TGGGCCAG

CACACACCCGTAACGCTGGACCTGCCTCCCCCCGCCGACACCCAGCAGAAACCTGTG CTGCCAGG

CCCGACCGCCGTTGTTGTAACCCGTCCTAGCCGCGCGTCCCTGCGCCGCGCCGCCAG CGGTCCGCG

ATCGTTGCGGCCCGTAGCCAGTGGCAACTGGCAAAGCACACTGAACAGCATCGTGGG TCTGGGGG

TGCAATCCCTGAAGCGCCGACGATGCTTCTGATAGCTAACGTGTCGTATGTGTGTCA TGTATGCGT

CCATGTCGCCGCCAGAGGAGCTGCTGAGCCGCCGCGCGCCCGCTTTCCAAGATGGCT ACCCCTTCG

ATGATGCCGCAGTGGTCTTACATGCACATCTCGGGCCAGGACGCCTCGGAGTACCTG AGCCCCGG

GCTGGTGCAGTTTGCCCGCGCCACCGAGACGTACTTCAGCCTGAATAACAAGTTTAG AAACCCCAC

GGTGGCGCCTACGCACGACGTGACCACAGACCGGTCCCAGCGTTTGACGCTGCGGTT CATCCCTGT

GGACCGTGAGGATACTGCGTACTCGTACAAGGCGCGGTTCACCCTAGCTGTGGGTGA TAACCGTGT

GCTGGACATGGCTTCCACGTACTTTGACATCCGCGGCGTGCTGGACAGGGGCCCTAC TTTTAAGCC

CTACTCTGGCACTGCCTACAACGCCCTGGCTCCCAAGGGTGCCCCAAATCCTTGCGA ATGGGATGA

AGCTGCTACTGCTCTTGAAATAAACCTAGAAGAAGAGGACGATGACAACGAAGACGA AGTAGAC

G AGC A AGCTG AGC AGC A A A A A ACTC ACGT ATTTGGGC AGGCGCCTT ATTCTGGT AT A A AT ATT AC

A A AGG AGGGT ATTC A A AT AGGTGTCG A AGGTC A A AC ACCT A A AT ATGCCG AT A A A AC ATTTC A AC

CTGAACCTCAAATAGGAGAATCTCAGTGGTACGAAACAGAAATTAATCATGCAGCTG GGAGAGTC

CTAAAAAAGACTACCCCAATGAAACCATGTTACGGTTCATATGCAAAACCCACAAAT GAAAATGG

AGGGCAAGGCATTCTTGTAAAGCAACAAAATGGAAAGCTAGAAAGTCAAGTGGAAAT GCAATTTT

TCTCAACTACTGAGGCAGCCGCAGGCAATGGTGATAACTTGACTCCTAAAGTGGTAT TGTACAGTG

A AG ATGT AG AT AT AG A A ACCCC AG AC ACTC AT ATTTCTT AC ATGCCC ACT ATTA AGG A AGGT A ACT

C ACG AG A ACT A ATGGGCC A AC A ATCT ATGCCC A AC AGGCCT A ATT AC ATTGCTTTT AGGG AC A ATT

TTATTGGTCTAATGTATTACAACAGCACGGGTAATATGGGTGTTCTGGCGGGCCAAG CATCGCAGT

TGAATGCTGTTGTAGATTTGCAAGACAGAAACACAGAGCTTTCATACCAGCTTTTGC TTGATTCCA

TTGGTGATAGAACCAGGTACTTTTCTATGTGGAATCAGGCTGTTGACAGCTATGATC CAGATGTTA

GAATTATTGAAAATCATGGAACTGAAGATGAACTTCCAAATTACTGCTTTCCACTGG GAGGTGTGA

TTAATACAGAGACTCTTACCAAGGTAAAACCTAAAACAGGTCAGGAAAATGGATGGG AAAAAGAT

GCTACAGAATTTTCAGATAAAAATGAAATAAGAGTTGGAAATAATTTTGCCATGGAA ATCAATCT

AAATGCCAACCTGTGGAGAAATTTCCTGTACTCCAACATAGCGCTGTATTTGCCCGA CAAGCTAAA GT AC AGTCCTTCC A ACGT A A A A ATTTCTG AT A ACCC A A AC ACCT ACG ACT AC ATG A AC A AGCG AGT

GGTGGCTCCCGGGCTAGTGGACTGCTACATTAACCTTGGAGCACGCTGGTCCCTTGA CTATATGGA

CAACGTCAACCCATTTAACCACCACCGCAATGCTGGCCTGCGCTACCGCTCAATGTT GCTGGGCAA

TGGTCGCTATGTGCCCTTCCACATCCAGGTGCCTCAGAAGTTCTTTGCCATTAAAAA CCTCCTTCTC

CTGCCGGGCTCATACACCTACGAGTGGAACTTCAGGAAGGATGTTAACATGGTTCTG CAGAGCTCC

CT AGG A A ATG ACCT A AGGGTTG ACGG AGCC AGC ATT A AGTTTG AT AGC ATTTGCCTTT ACGCC ACC

TTCTTCCCCATGGCCCACAACACCGCCTCCACGCTTGAGGCCATGCTTAGAAACGAC ACCAACGAC

C AGTCCTTT AACG ACT ATCTCTCCGCCGCC A AC ATGCTCT ACCCT AT ACCCGCC A ACGCT ACC A AC

GTGCCCATATCCATCCCCTCCCGCAACTGGGCGGCTTTCCGCGGCTGGGCCTTCACG CGCCTTAAG

ACT A AGG A A ACCCC ATC ACTGGGCTCGGGCT ACG ACCCTT ATT AC ACCT ACTCTGGCTCT AT ACCC

TACCTAGATGGAACCTTTTACCTCAACCACACCTTTAAGAAGGTGGCCATTACCTTT GACTCTTCTG

TCAGCTGGCCTGGCAATGACCGCCTGCTTACCCCCAACGAGTTTGAAATTAAGCGCT CAGTTGACG

GGGAGGGTTACAACGTTGCCCAGTGTAACATGACCAAAGACTGGTTCCTGGTACAAA TGCTAGCT

A ACT AT A AC ATTGGCT ACC AGGGCTTCT AT ATCCC AG AG AGCT AC A AGG ACCGC ATGT ACTCCTTC

TTTAGAAACTTCCAGCCCATGAGCCGTCAGGTGGTGGATGATACTAAATACAAGGAC TACCAACA

GGTGGGCATCCTACACCAACACAACAACTCTGGATTTGTTGGCTACCTTGCCCCCAC CATGCGCGA

AGG AC AGGCCT ACCCTGCT A ACTTCCCCT ATCCGCTT AT AGGC A AG ACCGC AGTTG AC AGC ATT AC

CCAGAAAAAGTTTCTTTGCGATCGCACCCTTTGGCGCATCCCATTCTCCAGTAACTT TATGTCCATG

GGCGCACTCACAGACCTGGGCCAAAACCTTCTCTACGCCAACTCCGCCCACGCGCTA GACATGACT

TTTGAGGTGGATCCCATGGACGAGCCCACCCTTCTTTATGTTTTGTTTGAAGTCTTT GACGTGGTCC

GTGTGCACCAGCCGCACCGCGGCGTCATCGAAACCGTGTACCTGCGCACGCCCTTCT CGGCCGGCA

ACGCCACAACATAAAGAAGCAAGCAACATCAACAACAGCTGCCGCCATGGGCTCCAG TGAGCAG

GAACTGAAAGCCATTGTCAAAGATCTTGGTTGTGGGCCATATTTTTTGGGCACCTAT GACAAGCGC

TTTCCAGGCTTTGTTTCTCCACACAAGCTCGCCTGCGCCATAGTCAATACGGCCGGT CGCGAGACT

GGGGGCGTACACTGGATGGCCTTTGCCTGGAACCCGCACTCAAAAACATGCTACCTC TTTGAGCCC

TTTGGCTTTTCTGACCAGCGACTCAAGCAGGTTTACCAGTTTGAGTACGAGTCACTC CTGCGCCGT

AGCGCCATTGCTTCTTCCCCCGACCGCTGTATAACGCTGGAAAAGTCCACCCAAAGC GTACAGGGG

CCCAACTCGGCCGCCTGTGGACTATTCTGCTGCATGTTTCTCCACGCCTTTGCCAAC TGGCCCCAAA

CTCCCATGGATCACAACCCCACCATGAACCTTATTACCGGGGTACCCAACTCCATGC TCAACAGTC

CCCAGGTACAGCCCACCCTGCGTCGCAACCAGGAACAGCTCTACAGCTTCCTGGAGC GCCACTCGC

CCTACTTCCGCAGCCACAGTGCGCAGATTAGGAGCGCCACTTCTTTTTGTCACTTGA AAAACATGT

AAAAATAATGTACTAGAGACACTTTCAATAAAGGCAAATGCTTTTATTTGTACACTC TCGGGTGAT

TATTTACCCCCACCCTTGCCGTCTGCGCCGTTTAAAAATCAAAGGGGTTCTGCCGCG CATCGCTAT

GCGCCACTGGCAGGGACACGTTGCGATACTGGTGTTTAGTGCTCCACTTAAACTCAG GCACAACCA

TCCGCGGCAGCTCGGTGAAGTTTTCACTCCACAGGCTGCGCACCATCACCAACGCGT TTAGCAGGT

CGGGCGCCGATATCTTGAAGTCGCAGTTGGGGCCTCCGCCCTGCGCGCGCGAGTTGC GATACACA

GGGTTGCAGCACTGGAACACTATCAGCGCCGGGTGGTGCACGCTGGCCAGCACGCTC TTGTCGGA

GATCAGATCCGCGTCCAGGTCCTCCGCGTTGCTCAGGGCGAACGGAGTCAACTTTGG TAGCTGCCT

TCCCAAAAAGGGCGCGTGCCCAGGCTTTGAGTTGCACTCGCACCGTAGTGGCATCAA AAGGTGAC

CGTGCCCGGTCTGGGCGTTAGGATACAGCGCCTGCATAAAAGCCTTGATCTGCTTAA AAGCCACCT

GAGCCTTTGCGCCTTCAGAGAAGAACATGCCGCAAGACTTGCCGGAAAACTGATTGG CCGGACAG

GCCGCGTCGTGCACGCAGCACCTTGCGTCGGTGTTGGAGATCTGCACCACATTTCGG CCCCACCGG

TTCTTCACGATCTTGGCCTTGCTAGACTGCTCCTTCAGCGCGCGCTGCCCGTTTTCG CTCGTCACAT

CC ATTTC A ATC ACGTGCTCCTT ATTT ATC AT A ATGCTTCCGTGT AG AC ACTT A AGCTCGCCTTCG AT

CTCAGCGCAGCGGTGCAGCCACAACGCGCAGCCCGTGGGCTCGTGATGCTTGTAGGT CACCTCTGC

AAACGACTGCAGGTACGCCTGCAGGAATCGCCCCATCATCGTCACAAAGGTCTTGTT GCTGGTGAA

GGTCAGCTGCAACCCGCGGTGCTCCTCGTTCAGCCAGGTCTTGCATACGGCCGCCAG AGCTTCCAC

TTGGTC AGGC AGT AGTTTG A AGTTCGCCTTT AG ATCGTT ATCC ACGTGGT ACTTGTCC ATC AGCGCG

CGCGCAGCCTCCATGCCCTTCTCCCACGCAGACACGATCGGCACACTCAGCGGGTTC ATCACCGTA

ATTTCACTTTCCGCTTCGCTGGGCTCTTCCTCTTCCTCTTGCGTCCGCATACCACGC GCCACTGGGT

CGTCTTCATTCAGCCGCCGCACTGTGCGCTTACCTCCTTTGCCATGCTTGATTAGCA CCGGTGGGTT

GCTGAAACCCACCATTTGTAGCGCCACATCTTCTCTTTCTTCCTCGCTGTCCACGAT TACTTTCACA

GGAGGTACAGCTATGACCATGATTACGGATTCACTGGCCGTCGTTTTACAACGTCGT GACTGGGAA

AACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGG CGTAATAGC

GAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATAG GTCGCGCC

GCACCGCGTCCGCGCTCGGGGGTGGTTTCGCGCTGCTCCTCTTCCCGACTGGCCATT TCCTTCTCCT

ATAGGCAGAAAAAGATCATGGAGTCAGTCGAGAAGAAGGACAGCCTAACCGCCCCCT CTGAGTTC

GCCACCACCGCCTCCACCGATGCCGCCAACGCGCCTACCACCTTCCCCGTCGAGGCA CCCCCGCTT

GAGGAGGAGGAAGTGATTATCGAGCAGGACCCAGGTTTTGTAAGCGAAGACGACGAG GACCGCT CAGTACCAACAGAGGATAAAAAGCAAGACCAGGACAACGCAGAGGCAAACGAGGAACAAG TCGG

GCGGGGGGACGAAAGGCATGGCGACTACCTAGATGTGGGAGACGACGTGCTGTTGAA GCATCTGC

AGCGCCAGTGCGCCATTATCTGCGACGCGTTGCAAGAGCGCAGCGATGTGCCCCTCG CCATAGCG

GATGTCAGCCTTGCCTACGAACGCCACCTATTCTCACCGCGCGTACCCCCCAAACGC CAAGAAAAC

GGCACATGCGAGCCCAACCCGCGCCTCAACTTCTACCCCGTATTTGCCGTGCCAGAG GTGCTTGCC

ACCTATCACATCTTTTTCCAAAACTGCAAGATACCCCTATCCTGCCGTGCCAACCGC AGCCGAGCG

GACAAGCAGCTGGCCTTGCGGCAGGGCGCTGTCATACCTGATATCGCCTCGCTCAAC GAAGTGCC

AAAAATCTTTGAGGGTCTTGGACGCGACGAGAAGCGCGCGGCAAACGCTCTGCAACA GGAAAACA

GCGAAAATGAAAGTCACTCTGGAGTGTTGGTGGAACTCGAGGGTGACAACGCGCGCC TAGCCGTA

CT AA A ACGC AGC ATCG AGGTC ACCC ACTTTGCCT ACCCGGC ACTT A ACCT ACCCCCC A AGGTC ATG

AGCACAGTCATGAGTGAGCTGATCGTGCGCCGTGCGCAGCCCCTGGAGAGGGATGCA AATTTGCA

AGAACAAACAGAGGAGGGCCTACCCGCAGTTGGCGACGAGCAGCTAGCGCGCTGGCT TCAAACGC

GCGAGCCTGCCGACTTGGAGGAGCGACGCAAACTAATGATGGCCGCAGTGCTCGTTA CCGTGGAG

CTTGAGTGCATGCAGCGGTTCTTTGCTGACCCGGAGATGCAGCGCAAGCTAGAGGAA ACATTGCA

CTACACCTTTCGACAGGGCTACGTACGCCAGGCCTGCAAGATCTCCAACGTGGAGCT CTGCAACCT

GGTCTCCTACCTTGGAATTTTGCACGAAAACCGCCTTGGGCAAAACGTGCTTCATTC CACGCTCAA

GGGCGAGGCGCGCCGCGACTACGTCCGCGACTGCGTTTACTTATTTCTATGCTACAC CTGGCAGAC

GGCCATGGGCGTTTGGCAGCAGTGCTTGGAGGAGTGCAACCTCAAGGAGCTGCAGAA ACTGCTAA

AGCAAAACTTGAAGGACCTATGGACGGCCTTCAACGAGCGCTCCGTGGCCGCGCACC TGGCGGAC

ATCATTTTCCCCGAACGCCTGCTTAAAACCCTGCAACAGGGTCTGCCAGACTTCACC AGTCAAAGC

ATGTTGCAGAACTTTAGGAACTTTATCCTAGAGCGCTCAGGAATCTTGCCCGCCACC TGCTGTGCA

CTTCCTAGCGACTTTGTGCCCATTAAGTACCGCGAATGCCCTCCGCCGCTTTGGGGC CACTGCTACC

TTCTGCAGCTAGCCAACTACCTTGCCTACCACTCTGACATAATGGAAGACGTGAGCG GTGACGGTC

TACTGGAGTGTCACTGTCGCTGCAACCTATGCACCCCGCACCGCTCCCTGGTTTGCA ATTCGCAGC

TGCTTAACGAAAGTCAAATTATCGGTACCTTTGAGCTGCAGGGTCCCTCGCCTGACG AAAAGTCCG

CGGCTCCGGGGTTGAAACTCACTCCGGGGCTGTGGACGTCGGCTTACCTTCGCAAAT TTGTACCTG

AGGACTACCACGCCCACGAGATTAGGTTCTACGAAGACCAATCCCGCCCGCCTAATG CGGAGCTT

ACCGCCTGCGTCATTACCCAGGGCCACATTCTTGGCCAATTGCAAGCCATCAACAAA GCCCGCCAA

GAGTTTCTGCTACGAAAGGGACGGGGGGTTTACTTGGACCCCCAGTCCGGCGAGGAG CTCAACCC

AATCCCCCCGCCGCCGCAGCCCTATCAGCAGCAGCCGCGGGCCCTTGCTTCCCAGGA TGGCACCCA

AAAAGAAGCTGCAGCTGCCGCCGCCACCCACGGACGAGGAGGAATACTGGGACAGTC AGGCAGA

GGAGGTTTTGGACGAGGAGGAGGAGGACATGATGGAAGACTGGGAGAGCCTAGACGA GGAAGCT

TCCGAGGTCGAAGAGGTGTCAGACGAAACACCGTCACCCTCGGTCGCATTCCCCTCG CCGGCGCCC

CAGAAATCGGCAACCGGTTCCAGCATGGCTACAACCTCCGCTCCTCAGGCGCCGCCG GCACTGCCC

GTTCGCCGACCCAACCGTAGATGGGACACCACTGGAACCAGGGCCGGTAAGTCCAAG CAGCCGCC

GCCGTTAGCCCAAGAGCAACAACAGCGCCAAGGCTACCGCTCATGGCGCGGGCACAA GAACGCCA

TAGTTGCTTGCTTGCAAGACTGTGGGGGCAACATCTCCTTCGCCCGCCGCTTTCTTC TCTACCATCA

CGGCGTGGCCTTCCCCCGT AAC ATCCTGC ATT ACT ACCGTC ATCTCT AC AGCCC AT ACTGC ACCGG

CGGCAGCGGCAGCAACAGCAGCGGCCACACAGAAGCAAAGGCGACCGGATAGCAAGA CTCTGAC

AAAGCCCAAGAAATCCACAGCGGCGGCAGCAGCAGGAGGAGGAGCGCTGCGTCTGGC GCCCAAC

G A ACCCGT ATCG ACCCGCG AGCTT AG A A AC AGG ATTTTTCCC ACTCTGT ATGCT AT ATTTC A AC AG

AGCAGGGGCCAAGAACAAGAGCTGAAAATAAAAAACAGGTCTCTGCGATCCCTCACC CGCAGCTG

CCTGTATCACAAAAGCGAAGATCAGCTTCGGCGCACGCTGGAAGACGCGGAGGCTCT CTTCAGTA

A AT ACTGCGCGCTG ACTCTT AAGG ACT AGTTTCGCGCCCTTTCTC A A ATTT A AGCGCG A A A ACT AC

GTCATCTCCAGCGGCCACACCCGGCGCCAGCACCTGTTGTCAGCGCCATTATGAGCA AGGAAATTC

CCACGCCCTACATGTGGAGTTACCAGCCACAAATGGGACTTGCGGCTGGAGCTGCCC AAGACTAC

TCAACCCGAATAAACTACATGAGCGCGGGACCCCACATGATATCCCGGGTCAACGGA ATACGCGC

CC ACCG A A ACCG A ATTCTCCTGG A AC AGGCGGCT ATT ACC ACC AC ACCTCGT A AT A ACCTT A ATCC

CCGTAGTTGGCCCGCTGCCCTGGTGTACCAGGAAAGTCCCGCTCCCACCACTGTGGT ACTTCCCAG

AGACGCCCAGGCCGAAGTTCAGATGACTAACTCAGGGGCGCAGCTTGCGGGCGGCTT TCGTCACA

GGGTGCGGTCGCCCGGGCAGGGTATAACTCACCTGACAATCAGAGGGCGAGGTATTC AGCTCAAC

GACGAGTCGGTGAGCTCCTCGCTTGGTCTCCGTCCGGACGGGACATTTCAGATCGGC GGCGCCGGC

CGCTCTTCATTCACGCCTCGTCAGGCAATCCTAACTCTGCAGACCTCGTCCTCTGAG CCGCGCTCTG

GAGGCATTGGAACTCTGCAATTTATTGAGGAGTTTGTGCCATCGGTCTACTTTAACC CCTTCTCGGG

ACCTCCCGGCCACTATCCGGATCAATTTATTCCTAACTTTGACGCGGTAAAGGACTC GGCGGACGG

CTACGACTGAATGTTAAGTGGAGAGGCAGAGCAACTGCGCCTGAAACACCTGGTCCA CTGTCGCC

GCCACAAGTGCTTTGCCCGCGACTCCGGTGAGTTTTGCTACTTTGAATTGCCCGAGG ATCATATCG

AGGGCCCGGCGCACGGCGTCCGGCTTACCGCCCAGGGAGAGCTTGCCCGTAGCCTGA TTCGGGAG

TTTACCCAGCGCCCCCTGCTAGTTGAGCGGGACAGGGGACCCTGTGTTCTCACTGTG ATTTGCAAC TGTCCTAACCCTGGATTACATCAAGATCTTTGTTGCCATCTCTGTGCTGAGTATAATAAA TACAGA

A ATT A A A AT AT ACTGGGGCTCCT ATCGCC ATCCTGT AA ACGCC ACCGTCTTC ACCCGCCC A AGC A A

ACCAAGGCGAACCTTACCTGGTACTTTTAACATCTCTCCCTCTGTGATTTACAACAG TTTCAACCCA

GACGGAGTGAGTCTACGAGAGAACCTCTCCGAGCTCAGCTACTCCATCAGAAAAAAC ACCACCCT

CCTTACCTGCCGGGAACGTACGAGTGCGTCACCGGCCGCTGCACCACACCTACCGCC TGACCGTAA

ACCAGACTTTTTCCGGACAGACCTCAATAACTCTGTTTACCAGAACAGGAGGTGAGC TTAGAAAAC

CCTTAGGGTATTAGGCCAAAGGCGCAGCTACTGTGGGGTTTATGAACAATTCAAGCA ACTCTACGG

GCT ATTCT A ATTC AGGTTTCTCT AG A A ATGG ACGG A ATT ATT AC AG AGC AGCGCCTGCT AG A A AG A

CGCAGGGCAGCGGCCGAGCAACAGCGCATGAATCAAGAGCTCCAAGACATGGTTAAC TTGCACCA

GTGCAAAAGGGGTATCTTTTGTCTGGTAAAGCAGGCCAAAGTCACCTACGACAGTAA TACCACCG

GACACCGCCTTAGCTACAAGTTGCCAACCAAGCGTCAGAAATTGGTGGTCATGGTGG GAGAAAAG

CCCATTACCATAACTCAGCACTCGGTAGAAACCGAAGGCTGCATTCACTCACCTTGT CAAGGACCT

GAGGATCTCTGCACCCTTATTAAGACCCTGTGCGGTCTCAAAGATCTTATTCCCTTT AACTAATAAA

A A A A A AT A AT A A AGC ATC ACTT ACTT A A A ATC AGTT AGC A A ATTTCTGTCC AGTTT ATTC AGC AGC

ACCTCCTTGCCCTCCTCCCAGCTCTGGTATTGCAGCTTCCTCCTGGCTGCAAACTTT CTCCACAATC

TAAATGGAATGTCAGTTTCCTCCTGTTCCTGTCCATCCGCACCCACTATCTTCATGT TGTTGCAGAT

GAAGCGCGCAAGACCGTCTGAAGATACCTTCAACCCCGTGTATCCATATGACACGGA AACCGGTC

CTCCAACTGTGCCTTTTCTTACTCCTCCCTTTGTATCCCCCAATGGGTTTCAAGAGA GTCCCCCTGG

GGTACTCTCTTTGCGCCTATCCGAACCTCTAGTTACCTCCAATGGCATGCTTGCGCT CAAAATGGGC

AACGGCCTCTCTCTGGACGAGGCCGGCAACCTTACCTCCCAAAATGTAACCACTGTG AGCCCACCT

CTCAAAAAAACCAAGTCAAACATAAACCTGGAAATATCTGCACCCCTCACAGTTACC TCAGAAGC

CCTAACTGTGGCTGCCGCCGCACCTCTAATGGTCGCGGGCAACACACTCACCATGCA ATCACAGGC

CCCGCTAACCGTGCACGACTCCAAACTTAGCATTGCCACCCAAGGACCCCTCACAGT GTCAGAAG

G A A AGCT AGCCCTGC A A AC ATC AGGCCCCCTC ACC ACC ACCG AT AGC AGT ACCCTT ACT ATC ACTG

CCTCACCCCCTCTAACTACTGCCACTGGTAGCTTGGGCATTGACTTGAAAGAGCCCA TTTATACAC

AAAATGGAAAACTAGGACTAAAGTACGGGGCTCCTTTGCATGTAACAGACGACCTAA ACACTTTG

ACCGTAGCAACTGGTCCAGGTGTGACTATTAATAATACTTCCTTGCAAACTAAAGTT ACTGGAGCC

TTGGGTTTTGATTCACAAGGCAATATGCAACTTAATGTAGCAGGAGGACTAAGGATT GATTCTCAA

A AC AG ACGCCTT AT ACTTG ATGTT AGTT ATCCGTTTG ATGCTC A A A ACC A ACT A A ATCT A AG ACT A

GG AC AGGGCCCTCTTTTTAT A A ACTC AGCCC AC A ACTTGG AT ATT AACT AC A AC A A AGGCCTTT AC

TTGTTTACAGCTTCAAACAATTCCAAAAAGCTTGAGGTTAACCTAAGCACTGCCAAG GGGTTGATG

TTTGACGCTACAGCCATAGCCATTAATGCAGGAGATGGGCTTGAATTTGGTTCACCT AATGCACCA

AACACAAATCCCCTCAAAACAAAAATTGGCCATGGCCTAGAATTTGATTCAAACAAG GCTATGGT

TCCT AA ACT AGG A ACTGGCCTT AGTTTTG AC AGC AC AGGTGCC ATT AC AGT AGG A A AC A A A A AT A

ATGATAAGCTAACTTTGTGGACCACACCAGCTCCATCTCCTAACTGTAGACTAAATG CAGAGAAAG

ATGCTAAACTCACTTTGGTCTTAACAAAATGTGGCAGTCAAATACTTGCTACAGTTT CAGTTTTGGC

TGTTAAAGGCAGTTTGGCTCCAATATCTGGAACAGTTCAAAGTGCTCATCTTATTAT AAGATTTGA

CGAAAATGGAGTGCTACTAAACAATTCCTTCCTGGACCCAGAATATTGGAACTTTAG AAATGGAG

ATCTT ACTG A AGGC AC AGCCT AT AC A A ACGCTGTTGG ATTT ATGCCT A ACCT ATC AGCTT ATCC A A

A ATCTC ACGGT A A A ACTGCC A A A AGT A AC ATTGTC AGTC A AGTTT ACTT A A ACGG AG AC A A A ACT

AAACCTGTAACACTAACCATTACACTAAACGGTACACAGGAAACAGGAGACACAACT CCAAGTGC

ATACTCTATGTCATTTTCATGGGACTGGTCTGGCCACAACTACATTAATGAAATATT TGCCACATCC

TCTTACACTTTTTCATACATTGCCCAAGAATAAAGAATCGTTTGTGTTATGTTTCAA CGTGTTTATT

TTTC A ATTGC AG A A A ATTTCG A ATC ATTTTTC ATTC AGT AGT AT AGCCCC ACC ACC AC AT AGCTT AT

AC AG ATC ACCGT ACCTT A ATC A A ACTC AC AG A ACCCT AGT ATTC A ACCTGCC ACCTCCCTCCC A AC

AC AC AG AGT AC AC AGTCCTTTCTCCCCGGCTGGCCTT A A A A AGC ATC AT ATC ATGGGT A AC AG AC A

T ATTCTT AGGTGTT AT ATTCC AC ACGGTTTCCTGTCG AGCC A A ACGCTC ATC AGTG AT ATT A AT AAA

CTCCCCGGGCAGCTCACTTAAGTTCATGTCGCTGTCCAGCTGCTGAGCCACAGGCTG CTGTCCAAC

TTGCGGTTGCTTAACGGGCGGCGAAGGAGAAGTCCACGCCTACATGGGGGTAGAGTC ATAATCGT

GCATCAGGATAGGGCGGTGGTGCTGCAGCAGCGCGCGAATAAACTGCTGCCGCCGCC GCTCCGTC

CTGCAGGAATACAACATGGCAGTGGTCTCCTCAGCGATGATTCGCACCGCCCGCAGC ATAAGGCG

CCTTGTCCTCCGGGCACAGCAGCGCACCCTGATCTCACTTAAATCAGCACAGTAACT GCAGCACAG

CACCACAATATTGTTCAAAATCCCACAGTGCAAGGCGCTGTATCCAAAGCTCATGGC GGGGACCA

CAGAACCCACGTGGCCATCATACCACAAGCGCAGGTAGATTAAGTGGCGACCCCTCA TAAACACG

CTGG AC AT A A AC ATT ACCTCTTTTGGC ATGTTGT A ATTC ACC ACCTCCCGGT ACC AT AT A A ACCTCT

GATTAAACATGGCGCCATCCACCACCATCCTAAACCAGCTGGCCAAAACCTGCCCGC CGGCTATAC

ACTGCAGGGAACCGGGACTGGAACAATGACAGTGGAGAGCCCAGGACTCGTAACCAT GGATCATC

ATGCTCGTCATGATATCAATGTTGGCACAACACAGGCACACGTGCATACACTTCCTC AGGATTACA

AGCTCCTCCCGCGTT AG A ACC AT ATCCC AGGG A AC A ACCC ATTCCTG A ATC AGCGT A A ATCCC AC A CTGCAGGGAAGACCTCGCACGTAACTCACGTTGTGCATTGTCAAAGTGTTACATTCGGGC AGCAGC

GGATGATCCTCCAGTATGGTAGCGCGGGTTTCTGTCTCAAAAGGAGGTAGACGATCC CTACTGTAC

GGAGTGCGCCGAGACAACCGAGATCGTGTTGGTCGTAGTGTCATGCCAAATGGAACG CCGGACGT

AGTCATATTTCCTGAAGCAAAACCAGGTGCGGGCGTGACAAACAGATCTGCGTCTCC GGTCTCGCC

GCTT AG ATCGCTCTGTGT AGT AGTTGT AGT AT ATCC ACTCTCTC A A AGC ATCC AGGCGCCCCCTGG

CTTCGGGTTCTATGTAAACTCCTTCATGCGCCGCTGCCCTGATAACATCCACCACCG CAGAATAAG

CCACACCCAGCCAACCTACACATTCGTTCTGCGAGTCACACACGGGAGGAGCGGGAA GAGCTGGA

AGAACCATGTTTTTTTTTTTATTCCAAAAGATTATCCAAAACCTCAAAATGAAGATC TATTAAGTG

AACGCGCTCCCCTCCGGTGGCGTGGTCAAACTCTACAGCCAAAGAACAGATAATGGC ATTTGTAA

GATGTTGCACAATGGCTTCCAAAAGGCAAACGGCCCTCACGTCCAAGTGGACGTAAA GGCTAAAC

CCTTCAGGGTGAATCTCCTCTATAAACATTCCAGCACCTTCAACCATGCCCAAATAA TTCTCATCTC

GCC ACCTTCTC A AT AT ATCTCT AAGC A A ATCCCG A AT ATT AAGTCCGGCC ATTGT A A A A ATCTGCT

CCAGAGCGCCCTCCACCTTCAGCCTCAAGCAGCGAATCATGATTGCAAAAATTCAGG TTCCTCACA

G ACCTGT AT AAG ATTC A A A AGCGG A AC ATT A AC A A A A AT ACCGCG ATCCCGT AGGTCCCTTCGC A

GGGCCAGCTGAACATAATCGTGCAGGTCTGCACGGACCAGCGCGGCCACTTCCCCGC CAGGAACC

ATGACAAAAGAACCCACACTGATTATGACACGCATACTCGGAGCTATGCTAACCAGC GTAGCCCC

GATGTAAGCTTGTTGCATGGGCGGCGATATAAAATGCAAGGTGCTGCTCAAAAAATC AGGCAAAG

CCTCGCGCAAAAAAGAAAGCACATCGTAGTCATGCTCATGCAGATAAAGGCAGGTAA GCTCCGGA

ACCACCACAGAAAAAGACACCATTTTTCTCTCAAACATGTCTGCGGGTTTCTGCATA AACACAAAA

T AAA AT A AC A A A A A A AC ATTT A A AC ATT AG A AGCCTGTCTT AC A AC AGG A A A A AC A ACCCTT AT A

AGCATAAGACGGACTACGGCCATGCCGGCGTGACCGTAAAAAAACTGGTCACCGTGA TTAAAAAG

CACCACCGACAGCTCCTCGGTCATGTCCGGAGTCATAATGTAAGACTCGGTAAACAC ATCAGGTTG

ATTCACATCGGTCAGTGCTAAAAAGCGACCGAAATAGCCCGGGGGAATACATACCCG CAGGCGTA

GAGACAACATTACAGCCCCCATAGGAGGTATAACAAAATTAATAGGAGAGAAAAACA CATAAAC

ACCTGAAAAACCCTCCTGCCTAGGCAAAATAGCACCCTCCCGCTCCAGAACAACATA CAGCGCTTC

C AC AGCGGC AGCC AT A AC AGTC AGCCTT ACC AGT A A A A A AG A A A ACCT ATT AAA A A A AC ACC ACT

CGACACGGCACCAGCTCAATCAGTCACAGTGTAAAAAAGGGCCAAGTGCAGAGCGAG TATATATA

GGACTAAAAAATGACGTAACGGTTAAAGTCCACAAAAAACACCCAGAAAACCGCACG CGAACCT

ACGCCCAGAAACGAAAGCCAAAAAACCCACAACTTCCTCAAATCGTCACTTCCGTTT TCCCACGTT

ACGTC ACTTCCC ATTTT AAG A A A ACT AC A ATTCCC A AC AC AT AC A AGTT ACTCCGCCCT A A A ACCT

ACGTCACCCGCCCCGTTCCCACGCCCCGCGCCACGTCACAAACTCCACCCCCTCATT ATCATATTG

GCTTC A ATCC A A A AT A AGGT AT ATT ATTG ATG ATGTT AATT AATTT A A ATCCGC ATGCG AT ATCG A

GCTCTCCCGGGAATTCGGATCTGCGACGCGAGGCTGGATGGCCTTCCCCATTATGAT TCTTCTCGC

GTTT AAGGGC ACC A AT A ACTGCCTT A A A A A A ATT ACGCCCCGCCCTGCC ACTC ATCGC AGT ACTGT

TGTAATTCATTAAGCATTCTGCCGACATGGAAGCCATCACAAACGGCATGATGAACC TGAATCGCC

AGCGGCATCAGCACCTTGTCGCCTTGCGTATAATATTTGCCCATGGTGAAAACGGGG GCGAAGAA

GTTGTCCATATTGGCCACGTTTAAATCAAAACTGGTGAAACTCACCCAGGGATTGGC TGAGACGAA

A A AC AT ATTCTC A AT A A ACCCTTT AGGG A A AT AGGCC AGGTTTTC ACCGT A AC ACGCC AC ATCTTG

CGAATATATGTGTAGAAACTGCCGGAAATCGTCGTGGTATTCACTCCAGAGCGATGA AAACGTTTC

AGTTTGCTCATGGAAAACGGTGTAACAAGGGTGAACACTATCCCATATCACCAGCTC ACCGTCTTT

CATTGCCATACGGAATTCCGGATGAGCATTCATCAGGCGGGCAAGAATGTGAATAAA GGCCGGAT

AAAACTTGTGCTTATTTTTCTTTACGGTCTTTAAAAAGGCCGTAATATCCAGCTGAA CGGTCTGGTT

ATAGGTACATTGAGCAACTGACTGAAATGCCTCAAAATGTTCTTTACGATGCCATTG GGATATATC

A ACGGTGGT AT ATCC AGTGATTTTTTTCTCC ATTTT AGCTTCCTT AGCTCCTG A A A ATCTCG AT A AC

TCAAAAAATACGCCCGGTAGTGATCTTATTTCATTATGGTGAAAGTTGGAACCTCTT ACGTGCCGA

TCAACGTCTCATTTTCGCCAAAAGTTGGCCCAGGGCTTCCCGGTATCAACAGGGACA CCAGGATTT

ATTT ATTCTGCG A AGTG ATCTTCCGTC AC AGGT ATTT ATTCGCG AT A AGCTC ATGG AGCGGCGT A A

CCGTCGCACAGGAAGGACAGAGAAAGCGCGGATCTGGGAAGTGACGGACAGAACGGT CAGGACC

TGGATTGGGGAGGCGGTTGCCGCCGCTGCTGCTGACGGTGTGACGTTCTCTGTTCCG GTCACACCA

CATACGTTCCGCCATTCCTATGCGATGCACATGCTGTATGCCGGTATACCGCTGAAA GTTCTGCAA

AGCCTGATGGGACATAAGTCCATCAGTTCAACGGAAGTCTACACGAAGGTTTTTGCG CTGGATGTG

GCTGCCCGGCACCGGGTGCAGTTTGCGATGCCGGAGTCTGATGCGGTTGCGATGCTG AAACAATTA

TCCTGAGAATAAATGCCTTGGCCTTTATATGGAAATGTGGAACTGAGTGGATATGCT GTTTTTGTCT

GTTAAACAGAGAAGCTGGCTGTTATCCACTGAGAAGCGAACGAAACAGTCGGGAAAA TCTCCCAT

T ATCGT AG AG ATCCGC ATT ATT A ATCTC AGG AGCCTGTGT AGCGTTT AT AGG A AGT AGTGTTCTGT

CATGATGCCTGCAAGCGGTAACGAAAACGATTTGAATATGCCTTCAGGAACAATAGA AATCTTCG

TGCGGTGTTACGTTGAAGTGGAGCGGATTATGTCAGCAATGGACAGAACAACCTAAT GAACACAG

AACCATGATGTGGTCTGTCCTTTTACAGCCAGTAGTGCTCGCCGCAGTCGAGCGACA GGGCGAAGC

CCTCGAGTGAGCGAGGAAGCACCAGGGAACAGCACTTATATATTCTGCTTACACACG ATGCCTGA A A A A ACTTCCCTTGGGGTT ATCC ACTT ATCC ACGGGG AT ATTTTT AT AATT ATTTTTTTT AT AGTTTT

TAGATCTTCTTTTTTAGAGCGCCTTGTAGGCCTTTATCCATGCTGGTTCTAGAGAAG GTGTTGTGAC

AAATTGCCCTTTCAGTGTGACAAATCACCCTCAAATGACAGTCCTGTCTGTGACAAA TTGCCCTTA

ACCCTGTGACAAATTGCCCTCAGAAGAAGCTGTTTTTTCACAAAGTTATCCCTGCTT ATTGACTCTT

TTTTATTTAGTGTGACAATCTAAAAACTTGTCACACTTCACATGGATCTGTCATGGC GGAAACAGC

GGTTATCAATCACAAGAAACGTAAAAATAGCCCGCGAATCGTCCAGTCAAACGACCT CACTGAGG

CGGCATATAGTCTCTCCCGGGATCAAAAACGTATGCTGTATCTGTTCGTTGACCAGA TCAGAAAAT

CTGATGGCACCCTACAGGAACATGACGGTATCTGCGAGATCCATGTTGCTAAATATG CTGAAATAT

TCGGATTGACCTCTGCGGAAGCCAGTAAGGATATACGGCAGGCATTGAAGAGTTTCG CGGGGAAG

GAAGTGGTTTTTTATCGCCCTGAAGAGGATGCCGGCGATGAAAAAGGCTATGAATCT TTTCCTTGG

TTT ATC A A ACGTGCGC AC AGTCC ATCC AG AGGGCTTT AC AGTGT AC AT ATC A ACCC AT ATCTC ATT

CCCTTCTTT ATCGGGTT AC AG A ACCGGTTT ACGC AGTTTCGGCTT AGTG A A AC A A A AG A A ATC ACC

AATCCGTATGCCATGCGTTTATACGAATCCCTGTGTCAGTATCGTAAGCCGGATGGC TCAGGCATC

GTCTCTCTGAAAATCGACTGGATCATAGAGCGTTACCAGCTGCCTCAAAGTTACCAG CGTATGCCT

GACTTCCGCCGCCGCTTCCTGCAGGTCTGTGTTAATGAGATCAACAGCAGAACTCCA ATGCGCCTC

TC AT AC ATTG AG A A A A AG A A AGGCCGCC AG ACG ACTC AT ATCGT ATTTTCCTTCCGCG AT ATC ACT

TCCATGACGACAGGATAGTCTGAGGGTTATCTGTCACAGATTTGAGGGTGGTTCGTC ACATTTGTT

CTGACCTACTGAGGGTAATTTGTCACAGTTTTGCTGTTTCCTTCAGCCTGCATGGAT TTTCTCATAC

TTTTTGAACTGTAATTTTTAAGGAAGCCAAATTTGAGGGCAGTTTGTCACAGTTGAT TTCCTTCTCT

TTCCCTTCGTCATGTGACCTGATATCGGGGGTTAGTTCGTCATCATTGATGAGGGTT GATTATCACA

GTTTATTACTCTGAATTGGCTATCCGCGTGTGTACCTCTACCTGGAGTTTTTCCCAC GGTGGATATT

TCTTCTTGCGCTGAGCGTAAGAGCTATCTGACAGAACAGTTCTTCTTTGCTTCCTCG CCAGTTCGCT

CGCTATGCTCGGTTACACGGCTGCGGCGAGCGCTAGTGATAATAAGTGACTGAGGTA TGTGCTCTT

CTTATCTCCTTTTGTAGTGTTGCTCTTATTTTAAACAACTTTGCGGTTTTTTGATGA CTTTGCGATTT

TGTTGTTGCTTTGCAGTAAATTGCAAGATTTAATAAAAAAACGCAAAGCAATGATTA AAGGATGTT

CAGAATGAAACTCATGGAAACACTTAACCAGTGCATAAACGCTGGTCATGAAATGAC GAAGGCTA

TCGCCATTGCACAGTTTAATGATGACAGCCCGGAAGCGAGGAAAATAACCCGGCGCT GGAGAATA

GGTGAAGCAGCGGATTTAGTTGGGGTTTCTTCTCAGGCTATCAGAGATGCCGAGAAA GCAGGGCG

ACTACCGCACCCGGATATGGAAATTCGAGGACGGGTTGAGCAACGTGTTGGTTATAC AATTGAAC

AAATTAATCATATGCGTGATGTGTTTGGTACGCGATTGCGACGTGCTGAAGACGTAT TTCCACCGG

TGATCGGGGTTGCTGCCCATAAAGGTGGCGTTTACAAAACCTCAGTTTCTGTTCATC TTGCTCAGG

ATCTGGCTCTGAAGGGGCTACGTGTTTTGCTCGTGGAAGGTAACGACCCCCAGGGAA CAGCCTCA

ATGTATCACGGATGGGTACCAGATCTTCATATTCATGCAGAAGACACTCTCCTGCCT TTCTATCTTG

GGGAAAAGGACGATGTCACTTATGCAATAAAGCCCACTTGCTGGCCGGGGCTTGACA TTATTCCTT

CCTGTCTGGCTCTGCACCGTATTGAAACTGAGTTAATGGGCAAATTTGATGAAGGTA AACTGCCCA

CCGATCCACACCTGATGCTCCGACTGGCCATTGAAACTGTTGCTCATGACTATGATG TCATAGTTA

TTGACAGCGCGCCTAACCTGGGTATCGGCACGATTAATGTCGTATGTGCTGCTGATG TGCTGATTG

TTCCCACGCCTGCTGAGTTGTTTGACTACACCTCCGCACTGCAGTTTTTCGATATGC TTCGTGATCT

GCTCAAGAACGTTGATCTTAAAGGGTTCGAGCCTGATGTACGTATTTTGCTTACCAA ATACAGCAA

TAGTAATGGCTCTCAGTCCCCGTGGATGGAGGAGCAAATTCGGGATGCCTGGGGAAG CATGGTTC

TAAAAAATGTTGTACGTGAAACGGATGAAGTTGGTAAAGGTCAGATCCGGATGAGAA CTGTTTTT

GAACAGGCCATTGATCAACGCTCTTCAACTGGTGCCTGGAGAAATGCTCTTTCTATT TGGGAACCT

GTCTGCAATGAAATTTTCGATCGTCTGATTAAACCACGCTGGGAGATTAGATAATGA AGCGTGCGC

CTGTT ATTCC A A A AC AT ACGCTC A AT ACTC A ACCGGTTG A AG AT ACTTCGTT ATCG AC ACC AGCTG

CCCCGATGGTGGATTCGTTAATTGCGCGCGTAGGAGTAATGGCTCGCGGTAATGCCA TTACTTTGC

CTGTATGTGGTCGGGATGTGAAGTTTACTCTTGAAGTGCTCCGGGGTGATAGTGTTG AGAAGACCT

CTCGGGTATGGTCAGGTAATGAACGTGACCAGGAGCTGCTTACTGAGGACGCACTGG ATGATCTC

ATCCCTTCTTTTCTACTGACTGGTCAACAGACACCGGCGTTCGGTCGAAGAGTATCT GGTGTCATA

GAAATTGCCGATGGGAGTCGCCGTCGTAAAGCTGCTGCACTTACCGAAAGTGATTAT CGTGTTCTG

GTTGGCGAGCTGGATGATGAGCAGATGGCTGCATTATCCAGATTGGGTAACGATTAT CGCCCAAC

AAGTGCTTATGAACGTGGTCAGCGTTATGCAAGCCGATTGCAGAATGAATTTGCTGG AAATATTTC

TGCGCTGGCTGATGCGGAAAATATTTCACGTAAGATTATTACCCGCTGTATCAACAC CGCCAAATT

GCCTAAATCAGTTGTTGCTCTTTTTTCTCACCCCGGTGAACTATCTGCCCGGTCAGG TGATGCACTT

C A A A A AGCCTTT AC AG AT A A AG AGG A ATT ACTT AAGC AGC AGGC ATCT A ACCTTC ATG AGC AG A A

AAAAGCTGGGGTGATATTTGAAGCTGAAGAAGTTATCACTCTTTTAACTTCTGTGCT TAAAACGTC

ATCTGCATCAAGAACTAGTTTAAGCTCACGACATCAGTTTGCTCCTGGAGCGACAGT ATTGTATAA

GGGCGATAAAATGGTGCTTAACCTGGACAGGTCTCGTGTTCCAACTGAGTGTATAGA GAAAATTG

AGGCCATTCTTAAGGAACTTGAAAAGCCAGCACCCTGATGCGACCACGTTTTAGTCT ACGTTTATC

TGTCTTTACTTAATGTCCTTTGTTACAGGCCAGAAAGCATAACTGGCCTGAATATTC TCTCTGGGCC CACTGTTCCACTTGTATCGTCGGTCTGATAATCAGACTGGGACCACGGTCCCACTCGTAT CGTCGG

TCTGATTATTAGTCTGGGACCACGGTCCCACTCGTATCGTCGGTCTGATTATTAGTC TGGGACCACG

GTCCCACTCGTATCGTCGGTCTGATAATCAGACTGGGACCACGGTCCCACTCGTATC GTCGGTCTG

ATT ATT AGTCTGGG ACC ATGGTCCC ACTCGT ATCGTCGGTCTG ATT ATT AGTCTGGG ACC ACGGTCC

C ACTCGT ATCGTCGGTCTG ATT ATT AGTCTGG A ACC ACGGTCCC ACTCGT ATCGTCGGTCTG ATT AT

TAGTCTGGGACCACGGTCCCACTCGTATCGTCGGTCTGATTATTAGTCTGGGACCAC GATCCCACT

CGTGTTGTCGGTCTGATTATCGGTCTGGGACCACGGTCCCACTTGTATTGTCGATCA GACTATCAGC

GTGAGACTACGATTCCATCAATGCCTGTCAAGGGCAAGTATTGACATGTCGTCGTAA CCTGTAGAA

CGGAGTAACCTCGGTGTGCGGTTGTATGCCTGCTGTGGATTGCTGCTGTGTCCTGCT TATCCACAAC

ATTTTGCGCACGGTTATGTGGACAAAATACCTGGTTACCCAGGCCGTGCCGGCACGT TAACCGGGC

AC ATTTCCCCG A A A AGTGCC ACCTG ACGTCT A AG A A ACC ATT ATT ATC ATG AC ATT A ACCT AT AAA

AATAGGCGTATCACGAGGCCCTTTCGTCTTCAAGAATTGGATCCGAATTCCCGGGAG AGCTCGATA

TCGC ATGCGG ATTT AA ATT AATT AA

* C1E (SEQ ID NO: 86)

CATCATCAATAATATACCTTATTTTGGATTGAAGCCAATATGATAATGAGGGGGTGGAGT TTGTGA

CGTGGCGCGGGGCGTGGGAACGGGGCGGGTGACGTAGTAGTGTGGCGGAAGTGTGAT GTTGCAAG

TGTGGCGGAACACATGTAAGCGACGGATGTGGCAAAAGTGACGTTTTTGGTGTGCGC CGGTGTAC

ACAGGAAGTGACAATTTTCGCGCGGTTTTAGGCGGATGTTGTAGTAAATTTGGGCGT AACCGAGTA

AGATTTGGCCATTTTCGCGGGAAAACTGAATAAGAGGAAGTGAAATCTGAATAATTT TGTGTTACT

CATAGCGCGTAATATTTGTCTAGGGCCGCGGGGACTTTGACCGTTTACGTGGAGACT CGCCCAGGT

GTTTTTCTC AGGTGTTTTCCGCGTTCCGGGTC A A AGTTGGCGTTTT ATT ATT AT AGTC AGTCG A AGC

TTGGATCCGGTACCTCTAGAATTCTCGAGCGGCCGCTAGCGACATCGGATCTCCCGA TCCCCTATG

GTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGTATCTGCTCCC TGCTTGTGTG

TTGGAGGTCGCTGAGTAGTGCGCGAGCAAAATTTAAGCTACAACAAGGCAAGGCTTG ACCGACAA

TTGCATGAAGAATCTGCTTAGGGTTAGGCGTTTTGCGCTGCTTCGCGATGTACGGGC CAGATATAC

GCGTTG AC ATTG ATT ATTG ACT AGTT ATT AAT AGT A ATC A ATT ACGGGGTC ATT AGTTC AT AGCCC

ATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCC CAACGACCC

CCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTT CCATTGACG

TCAATGGGTGGACTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCA TATGCCAAG

TACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTA CATGACCTT

ATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGT GATGCGGTTT

TGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTC CACCCCATT

GACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGT AACAACTCC

GCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGA GCTCTCTG

GCT A ACT AG AG A ACCC ACTGCTT ACTGGCTT ATCGA A ATT AAT ACG ACTC ACT AT AGGG AG ACCC A

AGCTGGCT AGTT A AGCT ATC A AC A AGTTTGT AC A A A A A AGC AGGCTTT A A AGG A ACC A ATTC AGT

CGACTGGATCCGGTACCACCATGTTCCTGAACTGCTGCCCAGGTTGCTGTATGGAGC CTGAATTCA

CCATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGC TGGACGGC

GACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTAC GGCAAGCT

GACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGT GACCACCCT

GACCTGGGGCGTGCAGTGCTTCGCCCGCTACCCCGACCACATGAAGCAGCACGACTT CTTCAAGTC

CGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAA CTACAAGA

CCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGG GCATCGAC

TTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACGCCATCAGCGAC AACGTCTA

TATCACCGCCGACAAGCAGAAGAACGGCATCAAGGCCAACTTCAAGATCCGCCACAA CATCGAGG

ACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCC CCGTGCTG

CTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAG AAGCGCGA

TCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGA GCTGTACAA

GGTCGACTATCCGTACGACGTACCAGACTACGCATAACCGCGGCCGCACTCGAGATA TCTAGACC

CAGCTTTCTTGTACAAAGTGGTTGATCTAGAGGGCCCGCGGTTCGAAGGTAAGCCTA TCCCTAACC

CTCTCCTCGGTCTCGATTCTACGCGTACCGGTTAGTAATGAGTTTAAACGGGGGAGG CTAACTGAA

ACACGGAAGGAGACAATACCGGAAGGAACCCGCGCTATGACGGCAATAAAAAGACAG AATAAAA

CGCACGGGTGTTGGGTCGTTTGTTCATAAACGCGGGGTTCGGTCCCAGGGCTGGCAC TCTGTCGAT

ACCCCACCGAGACCCCATTGGGGCCAATACGCCCGCGTTTCTTCCTTTTCCCCACCC CACCCCCCA

AGTTCGGGTGAAGGCCCAGGGCTCGCAGCCAACGTCGGGGCGGCAGGCCCTGCCATA GCAGATCC

GATTCGACAGATCACTGAAATGTGTGGGCGTGGCTTAAGGGTGGGAAAGAATATATA AGGTGGGG

GTCTTATGTAGTTTTGTATCTGTTTTGCAGCAGCCGCCGCCGCCATGAGCACCAACT CGTTTGATGG AAGCATTGTGAGCTCATATTTGACAACGCGCATGCCCCCATGGGCCGGGGTGCGTCAGAA TGTGAT

GGGCTCCAGCATTGATGGTCGCCCCGTCCTGCCCGCAAACTCTACTACCTTGACCTA CGAGACCGT

GTCTGGAACGCCGTTGGAGACTGCAGCCTCCGCCGCCGCTTCAGCCGCTGCAGCCAC CGCCCGCGG

GATTGTGACTGACTTTGCTTTCCTGAGCCCGCTTGCAAGCAGTGCAGCTTCCCGTTC ATCCGCCCGC

GATGACAAGTTGACGGCTCTTTTGGCACAATTGGATTCTTTGACCCGGGAACTTAAT GTCGTTTCTC

AGCAGCTGTTGGATCTGCGCCAGCAGGTTTCTGCCCTGAAGGCTTCCTCCCCTCCCA ATGCGGTTT

AAAACATAAATAAAAAACCAGACTCTGTTTGGATTTGGATCAAGCAAGTGTCTTGCT GTCTTTATT

TAGGGGTTTTGCGCGCGCGGTAGGCCCGGGACCAGCGGTCTCGGTCGTTGAGGGTCC TGTGTATTT

TTTCCAGGACGTGGTAAAGGTGACTCTGGATGTTCAGATACATGGGCATAAGCCCGT CTCTGGGGT

GGAGGTAGCACCACTGCAGAGCTTCATGCTGCGGGGTGGTGTTGTAGATGATCCAGT CGTAGCAG

GAGCGCTGGGCGTGGTGCCTAAAAATGTCTTTCAGTAGCAAGCTGATTGCCAGGGGC AGGCCCTT

GGTGTAAGTGTTTACAAAGCGGTTAAGCTGGGATGGGTGCATACGTGGGGATATGAG ATGCATCT

TGGACTGTATTTTTAGGTTGGCTATGTTCCCAGCCATATCCCTCCGGGGATTCATGT TGTGCAGAAC

CACCAGCACAGTGTATCCGGTGCACTTGGGAAATTTGTCATGTAGCTTAGAAGGAAA TGCGTGGA

AGAACTTGGAGACGCCCTTGTGACCTCCAAGATTTTCCATGCATTCGTCCATAATGA TGGCAATGG

GCCCACGGGCGGCGGCCTGGGCGAAGATATTTCTGGGATCACTAACGTCATAGTTGT GTTCCAGGA

TGAGATCGTCATAGGCCATTTTTACAAAGCGCGGGCGGAGGGTGCCAGACTGCGGTA TAATGGTT

CCATCCGGCCCAGGGGCGTAGTTACCCTCACAGATTTGCATTTCCCACGCTTTGAGT TCAGATGGG

GGGATCATGTCTACCTGCGGGGCGATGAAGAAAACGGTTTCCGGGGTAGGGGAGATC AGCTGGGA

AGAAAGCAGGTTCCTGAGCAGCTGCGACTTACCGCAGCCGGTGGGCCCGTAAATCAC ACCTATTA

CCGGCTGCAACTGGTAGTTAAGAGAGCTGCAGCTGCCGTCATCCCTGAGCAGGGGGG CCACTTCG

TTAAGCATGTCCCTGACTCGCATGTTTTCCCTGACCAAATCCGCCAGAAGGCGCTCG CCGCCCAGC

GATAGCAGTTCTTGCAAGGAAGCAAAGTTTTTCAACGGTTTGAGACCGTCCGCCGTA GGCATGCTT

TTGAGCGTTTGACCAAGCAGTTCCAGGCGGTCCCACAGCTCGGTCACCTGCTCTACG GCATCTCGA

TCCAGCATATCTCCTCGTTTCGCGGGTTGGGGCGGCTTTCGCTGTACGGCAGTAGTC GGTGCTCGTC

CAGACGGGCCAGGGTCATGTCTTTCCACGGGCGCAGGGTCCTCGTCAGCGTAGTCTG GGTCACGGT

GAAGGGGTGCGCTCCGGGCTGCGCGCTGGCCAGGGTGCGCTTGAGGCTGGTCCTGCT GGTGCTGA

AGCGCTGCCGGTCTTCGCCCTGCGCGTCGGCCAGGTAGCATTTGACCATGGTGTCAT AGTCCAGCC

CCTCCGCGGCGTGGCCCTTGGCGCGCAGCTTGCCCTTGGAGGAGGCGCCGCACGAGG GGCAGTGC

AGACTTTTGAGGGCGTAGAGCTTGGGCGCGAGAAATACCGATTCCGGGGAGTAGGCA TCCGCGCC

GCAGGCCCCGCAGACGGTCTCGCATTCCACGAGCCAGGTGAGCTCTGGCCGTTCGGG GTCAAAAA

CCAGGTTTCCCCCATGCTTTTTGATGCGTTTCTTACCTCTGGTTTCCATGAGCCGGT GTCCACGCTC

GGTGACGAAAAGGCTGTCCGTGTCCCCGTATACAGACTTGAGAGGCCTGTCCTCGAG CGGTGTTCC

GCGGTCCTCCTCGTATAGAAACTCGGACCACTCTGAGACAAAGGCTCGCGTCCAGGC CAGCACGA

AGGAGGCTAAGTGGGAGGGGTAGCGGTCGTTGTCCACTAGGGGGTCCACTCGCTCCA GGGTGTGA

AGACACATGTCGCCCTCTTCGGCATCAAGGAAGGTGATTGGTTTGTAGGTGTAGGCC ACGTGACCG

GGTGTTCCTGAAGGGGGGCTATAAAAGGGGGTGGGGGCGCGTTCGTCCTCACTCTCT TCCGCATCG

CTGTCTGCGAGGGCCAGCTGTTGGGGTGAGTACTCCCTCTGAAAAGCGGGCATGACT TCTGCGCTA

AGATTGTCAGTTTCCAAAAACGAGGAGGATTTGATATTCACCTGGCCCGCGGTGATG CCTTTGAGG

GTGGCCGCATCCATCTGGTCAGAAAAGACAATCTTTTTGTTGTCAAGCTTGGTGGCA AACGACCCG

TAGAGGGCGTTGGACAGCAACTTGGCGATGGAGCGCAGGGTTTGGTTTTTGTCGCGA TCGGCGCG

CTCCTTGGCCGCGATGTTTAGCTGCACGTATTCGCGCGCAACGCACCGCCATTCGGG AAAGACGGT

GGTGCGCTCGTCGGGCACCAGGTGCACGCGCCAACCGCGGTTGTGCAGGGTGACAAG GTCAACGC

TGGTGGCTACCTCTCCGCGTAGGCGCTCGTTGGTCCAGCAGAGGCGGCCGCCCTTGC GCGAGCAGA

ATGGCGGTAGGGGGTCTAGCTGCGTCTCGTCCGGGGGGTCTGCGTCCACGGTAAAGA CCCCGGGC

AGCAGGCGCGCGTCGAAGTAGTCTATCTTGCATCCTTGCAAGTCTAGCGCCTGCTGC CATGCGCGG

GCGGCAAGCGCGCGCTCGTATGGGTTGAGTGGGGGACCCCATGGCATGGGGTGGGTG AGCGCGGA

GGCGTACATGCCGCAAATGTCGTAAACGTAGAGGGGCTCTCTGAGTATTCCAAGATA TGTAGGGT

AGCATCTTCCACCGCGGATGCTGGCGCGCACGTAATCGTATAGTTCGTGCGAGGGAG CGAGGAGG

TCGGGACCGAGGTTGCTACGGGCGGGCTGCTCTGCTCGGAAGACTATCTGCCTGAAG ATGGCATGT

GAGTTGGATGATATGGTTGGACGCTGGAAGACGTTGAAGCTGGCGTCTGTGAGACCT ACCGCGTC

ACGCACGAAGGAGGCGTAGGAGTCGCGCAGCTTGTTGACCAGCTCGGCGGTGACCTG CACGTCTA

GGGCGCAGTAGTCCAGGGTTTCCTTGATGATGTCATACTTATCCTGTCCCTTTTTTT TCCACAGCTC

GCGGTTGAGGACAAACTCTTCGCGGTCTTTCCAGTACTCTTGGATCGGAAACCCGTC GGCCTCCGA

ACGGTAAGAGCCTAGCATGTAGAACTGGTTGACGGCCTGGTAGGCGCAGCATCCCTT TTCTACGGG

TAGCGCGTATGCCTGCGCGGCCTTCCGGAGCGAGGTGTGGGTGAGCGCAAAGGTGTC CCTGACCA

TGACCAGCATGAAGGGCACGAGCTGCTTCCCAAAGGCCCCCATCCAAGTATAGGTCT CTACATCGT

AGGTGACAAAGAGACGCTCGGTGCGAGGATGCGAGCCGATCGGGAAGAACTGGATCT CCCGCCAC

CAATTGGAGGAGTGGCTATTGATGTGGTGAAAGTAGAAGTCCCTGCGACGGGCCGAA CACTCGTG CTGGCTTTTGTAAAAACGTGCGCAGTACTGGCAGCGGTGCACGGGCTGTACATCCTGCAC GAGGTT

GACCTGACGACCGCGCACAAGGAAGCAGAGTGGGAATTTGAGCCCCTCGCCTGGCGG GTTTGGCT

GGTGGTCTTCTACTTCGGCTGCTTGTCCTTGACCGTCTGGCTGCTCGAGGGGAGTTA CGGTGGATC

GGACCACCACGCCGCGCGAGCCCAAAGTCCAGATGTCCGCGCGCGGCGGTCGGAGCT TGATGACA

ACATCGCGCAGATGGGAGCTGTCCATGGTCTGGAGCTCCCGCGGCGTCAGGTCAGGC GGGAGCTC

CTGCAGGTTTACCTCGCATAGACGGGTCAGGGCGCGGGCTAGATCCAGGTGATACCT AATTTCCAG

GGGCTGGTTGGTGGCGGCGTCGATGGCTTGCAAGAGGCCGCATCCCCGCGGCGCGAC TACGGTAC

CGCGCGGCGGGCGGTGGGCCGCGGGGGTGTCCTTGGATGATGCATCTAAAAGCGGTG ACGCGGGC

GAGCCCCCGGAGGTAGGGGGGGCTCCGGACCCGCCGGGAGAGGGGGCAGGGGCACGT CGGCGCC

GCGCGCGGGCAGGAGCTGGTGCTGCGCGCGTAGGTTGCTGGCGAACGCGACGACGCG GCGGTTGA

TCTCCTGAATCTGGCGCCTCTGCGTGAAGACGACGGGCCCGGTGAGCTTGAACCTGA AAGAGAGT

TCGACAGAATCAATTTCGGTGTCGTTGACGGCGGCCTGGCGCAAAATCTCCTGCACG TCTCCTGAG

TTGTCTTGATAGGCGATCTCGGCCATGAACTGCTCGATCTCTTCCTCCTGGAGATCT CCGCGTCCGG

CTCGCTCCACGGTGGCGGCGAGGTCGTTGGAAATGCGGGCCATGAGCTGCGAGAAGG CGTTGAGG

CCTCCCTCGTTCCAGACGCGGCTGTAGACCACGCCCCCTTCGGCATCGCGGGCGCGC ATGACCACC

TGCGCGAGATTGAGCTCCACGTGCCGGGCGAAGACGGCGTAGTTTCGCAGGCGCTGA AAGAGGTA

GTTGAGGGTGGTGGCGGTGTGTTCTGCCACGAAGAAGTACATAACCCAGCGTCGCAA CGTGGATT

CGTTGATATCCCCCAAGGCCTCAAGGCGCTCCATGGCCTCGTAGAAGTCCACGGCGA AGTTGAAA

AACTGGGAGTTGCGCGCCGACACGGTTAACTCCTCCTCCAGAAGACGGATGAGCTCG GCGACAGT

GTCGCGCACCTCGCGCTCAAAGGCTACAGGGGCCTCTTCTTCTTCTTCAATCTCCTC TTCCATAAGG

GCCTCCCCTTCTTCTTCTTCTGGCGGCGGTGGGGGAGGGGGGACACGGCGGCGACGA CGGCGCAC

CGGGAGGCGGTCGACAAAGCGCTCGATCATCTCCCCGCGGCGACGGCGCATGGTCTC GGTGACGG

CGCGGCCGTTCTCGCGGGGGCGCAGTTGGAAGACGCCGCCCGTCATGTCCCGGTTAT GGGTTGGCG

GGGGGCTGCCATGCGGCAGGGATACGGCGCTAACGATGCATCTCAACAATTGTTGTG TAGGTACT

CCGCCGCCGAGGGACCTGAGCGAGTCCGCATCGACCGGATCGGAAAACCTCTCGAGA AAGGCGTC

TAACCAGTCACAGTCGCAAGGTAGGCTGAGCACCGTGGCGGGCGGCAGCGGGCGGCG GTCGGGGT

TGTTTCTGGCGGAGGTGCTGCTGATGATGTAATTAAAGTAGGCGGTCTTGAGACGGC GGATGGTCG

ACAGAAGCACCATGTCCTTGGGTCCGGCCTGCTGAATGCGCAGGCGGTCGGCCATGC CCCAGGCTT

CGTTTTGACATCGGCGCAGGTCTTTGTAGTAGTCTTGCATGAGCCTTTCTACCGGCA CTTCTTCTTC

TCCTTCCTCTTGTCCTGCATCTCTTGCATCTATCGCTGCGGCGGCGGCGGAGTTTGG CCGTAGGTGG

CGCCCTCTTCCTCCCATGCGTGTGACCCCGAAGCCCCTCATCGGCTGAAGCAGGGCT AGGTCGGCG

ACAACGCGCTCGGCTAATATGGCCTGCTGCACCTGCGTGAGGGTAGACTGGAAGTCA TCCATGTCC

ACAAAGCGGTGGTATGCGCCCGTGTTGATGGTGTAAGTGCAGTTGGCCATAACGGAC CAGTTAAC

GGTCTGGTGACCCGGCTGCGAGAGCTCGGTGTACCTGAGACGCGAGTAAGCCCTCGA GTCAAATA

CGTAGTCGTTGCAAGTCCGCACCAGGTACTGGTATCCCACCAAAAAGTGCGGCGGCG GCTGGCGG

TAGAGGGGCCAGCGTAGGGTGGCCGGGGCTCCGGGGGCGAGATCTTCCAACATAAGG CGATGATA

TCCGTAGATGTACCTGGACATCCAGGTGATGCCGGCGGCGGTGGTGGAGGCGCGCGG AAAGTCGC

GGACGCGGTTCCAGATGTTGCGCAGCGGCAAAAAGTGCTCCATGGTCGGGACGCTCT GGCCGGTC

AGGCGCGCGCAATCGTTGACGCTCTAGACCGTGCAAAAGGAGAGCCTGTAAGCGGGC ACTCTTCC

GTGGTCTGGTGGATAAATTCGCAAGGGTATCATGGCGGACGACCGGGGTTCGAGCCC CGTATCCG

GCCGTCCGCCGTGATCCATGCGGTTACCGCCCGCGTGTCGAACCCAGGTGTGCGACG TCAGACAAC

GGGGGAGTGCTCCTTTTGGCTTCCTTCCAGGCGCGGCGGCTGCTGCGCTAGCTTTTT TGGCCACTGG

CCGCGCGCAGCGTAAGCGGTTAGGCTGGAAAGCGAAAGCATTAAGTGGCTCGCTCCC TGTAGCCG

GAGGGTTATTTTCCAAGGGTTGAGTCGCGGGACCCCCGGTTCGAGTCTCGGACCGGC CGGACTGCG

GCGAACGGGGGTTTGCCTCCCCGTCATGCAAGACCCCGCTTGCAAATTCCTCCGGAA ACAGGGAC

GAGCCCCTTTTTTGCTTTTCCCAGATGCATCCGGTGCTGCGGCAGATGCGCCCCCCT CCTCAGCAGC

GGCAAGAGCAAGAGCAGCGGCAGACATGCAGGGCACCCTCCCCTCCTCCTACCGCGT CAGGAGGG

GCGACATCCGCGGTTGACGCGGCAGCAGATGGTGATTACGAACCCCCGCGGCGCCGG GCCCGGCA

CTACCTGGACTTGGAGGAGGGCGAGGGCCTGGCGCGGCTAGGAGCGCCCTCTCCTGA GCGGCACC

CAAGGGTGCAGCTGAAGCGTGATACGCGTGAGGCGTACGTGCCGCGGCAGAACCTGT TTCGCGAC

CGCGAGGGAGAGGAGCCCGAGGAGATGCGGGATCGAAAGTTCCACGCAGGGCGCGAG CTGCGGC

ATGGCCTGAATCGCGAGCGGTTGCTGCGCGAGGAGGACTTTGAGCCCGACGCGCGAA CCGGGATT

AGTCCCGCGCGCGCACACGTGGCGGCCGCCGACCTGGTAACCGCATACGAGCAGACG GTGAACCA

GGAGATTAACTTTCAAAAAAGCTTTAACAACCACGTGCGTACGCTTGTGGCGCGCGA GGAGGTGG

CTATAGGACTGATGCATCTGTGGGACTTTGTAAGCGCGCTGGAGCAAAACCCAAATA GCAAGCCG

CTCATGGCGCAGCTGTTCCTTATAGTGCAGCACAGCAGGGACAACGAGGCATTCAGG GATGCGCT

GCTAAACATAGTAGAGCCCGAGGGCCGCTGGCTGCTCGATTTGATAAACATCCTGCA GAGCATAG

TGGTGCAGGAGCGCAGCTTGAGCCTGGCTGACAAGGTGGCCGCCATCAACTATTCCA TGCTTAGCC

TGGGCAAGTTTTACGCCCGCAAGATATACCATACCCCTTACGTTCCCATAGACAAGG AGGTAAAG ATCGAGGGGTTCTACATGCGCATGGCGCTGAAGGTGCTTACCTTGAGCGACGACCTGGGC GTTTAT

CGCAACGAGCGCATCCACAAGGCCGTGAGCGTGAGCCGGCGGCGCGAGCTCAGCGAC CGCGAGCT

GATGCACAGCCTGCAAAGGGCCCTGGCTGGCACGGGCAGCGGCGATAGAGAGGCCGA GTCCTACT

TTGACGCGGGCGCTGACCTGCGCTGGGCCCCAAGCCGACGCGCCCTGGAGGCAGCTG GGGCCGGA

CCTGGGCTGGCGGTGGCACCCGCGCGCGCTGGCAACGTCGGCGGCGTGGAGGAATAT GACGAGGA

CGATGAGTACGAGCCAGAGGACGGCGAGTACTAAGCGGTGATGTTTCTGATCAGATG ATGCAAGA

CGCAACGGACCCGGCGGTGCGGGCGGCGCTGCAGAGCCAGCCGTCCGGCCTTAACTC CACGGACG

ACTGGCGCCAGGTCATGGACCGCATCATGTCGCTGACTGCGCGCAATCCTGACGCGT TCCGGCAGC

AGCCGCAGGCCAACCGGCTCTCCGCAATTCTGGAAGCGGTGGTCCCGGCGCGCGCAA ACCCCACG

CACGAGAAGGTGCTGGCGATCGTAAACGCGCTGGCCGAAAACAGGGCCATCCGGCCC GACGAGG

CCGGCCTGGTCTACGACGCGCTGCTTCAGCGCGTGGCTCGTTACAACAGCGGCAACG TGCAGACC

AACCTGGACCGGCTGGTGGGGGATGTGCGCGAGGCCGTGGCGCAGCGTGAGCGCGCG CAGCAGC

AGGGCAACCTGGGCTCCATGGTTGCACTAAACGCCTTCCTGAGTACACAGCCCGCCA ACGTGCCGC

GGGGACAGGAGGACTACACCAACTTTGTGAGCGCACTGCGGCTAATGGTGACTGAGA CACCGCAA

AGTGAGGTGTACCAGTCTGGGCCAGACTATTTTTTCCAGACCAGTAGACAAGGCCTG CAGACCGTA

AACCTGAGCCAGGCTTTCAAAAACTTGCAGGGGCTGTGGGGGGTGCGGGCTCCCACA GGCGACCG

CGCGACCGTGTCTAGCTTGCTGACGCCCAACTCGCGCCTGTTGCTGCTGCTAATAGC GCCCTTCAC

GGACAGTGGCAGCGTGTCCCGGGACACATACCTAGGTCACTTGCTGACACTGTACCG CGAGGCCA

TAGGTCAGGCGCATGTGGACGAGCATACTTTCCAGGAGATTACAAGTGTCAGCCGCG CGCTGGGG

CAGGAGGACACGGGCAGCCTGGAGGCAACCCTAAACTACCTGCTGACCAACCGGCGG CAGAAGA

TCCCCTCGTTGCACAGTTTAAACAGCGAGGAGGAGCGCATTTTGCGCTACGTGCAGC AGAGCGTG

AGCCTTAACCTGATGCGCGACGGGGTAACGCCCAGCGTGGCGCTGGACATGACCGCG CGCAACAT

GGAACCGGGCATGTATGCCTCAAACCGGCCGTTTATCAACCGCCTAATGGACTACTT GCATCGCGC

GGCCGCCGTGAACCCCGAGTATTTCACCAATGCCATCTTGAACCCGCACTGGCTACC GCCCCCTGG

TTTCTACACCGGGGGATTCGAGGTGCCCGAGGGTAACGATGGATTCCTCTGGGACGA CATAGACG

ACAGCGTGTTTTCCCCGCAACCGCAGACCCTGCTAGAGTTGCAACAGCGCGAGCAGG CAGAGGCG

GCGCTGCGAAAGGAAAGCTTCCGCAGGCCAAGCAGCTTGTCCGATCTAGGCGCTGCG GCCCCGCG

GTC AG ATGCT AGT AGCCC ATTTCC A AGCTTG AT AGGGTCTCTT ACC AGC ACTCGC ACC ACCCGCCC

GCGCCTGCTGGGCGAGGAGGAGTACCTAAACAACTCGCTGCTGCAGCCGCAGCGCGA AAAAAACC

TGCCTCCGGCATTTCCCAACAACGGGATAGAGAGCCTAGTGGACAAGATGAGTAGAT GGAAGACG

TACGCGCAGGAGCACAGGGACGTGCCAGGCCCGCGCCCGCCCACCCGTCGTCAAAGG CACGACCG

TCAGCGGGGTCTGGTGTGGGAGGACGATGACTCGGCAGACGACAGCAGCGTCCTGGA TTTGGGAG

GGAGTGGCAACCCGTTTGCGCACCTTCGCCCCAGGCTGGGGAGAATGTTTTAAAAAA AAAAAAAG

CATGATGCAAAATAAAAAACTCACCAAGGCCATGGCACCGAGCGTTGGTTTTCTTGT ATTCCCCTT

AGTATGCGGCGCGCGGCGATGTATGAGGAAGGTCCTCCTCCCTCCTACGAGAGTGTG GTGAGCGC

GGCGCCAGTGGCGGCGGCGCTGGGTTCTCCCTTCGATGCTCCCCTGGACCCGCCGTT TGTGCCTCC

GCGGTACCTGCGGCCTACCGGGGGGAGAAACAGCATCCGTTACTCTGAGTTGGCACC CCTATTCGA

CACCACCCGTGTGTACCTGGTGGACAACAAGTCAACGGATGTGGCATCCCTGAACTA CCAGAACG

ACCACAGCAACTTTCTGACCACGGTCATTCAAAACAATGACTACAGCCCGGGGGAGG CAAGCACA

CAGACCATCAATCTTGACGACCGGTCGCACTGGGGCGGCGACCTGAAAACCATCCTG CATACCAA

CATGCCAAATGTGAACGAGTTCATGTTTACCAATAAGTTTAAGGCGCGGGTGATGGT GTCGCGCTT

GCCTACTAAGGACAATCAGGTGGAGCTGAAATACGAGTGGGTGGAGTTCACGCTGCC CGAGGGCA

ACTACTCCGAGACCATGACCATAGACCTTATGAACAACGCGATCGTGGAGCACTACT TGAAAGTG

GGCAGACAGAACGGGGTTCTGGAAAGCGACATCGGGGTAAAGTTTGACACCCGCAAC TTCAGACT

GGGGTTTGACCCCGTCACTGGTCTTGTCATGCCTGGGGTATATACAAACGAAGCCTT CCATCCAGA

CATCATTTTGCTGCCAGGATGCGGGGTGGACTTCACCCACAGCCGCCTGAGCAACTT GTTGGGCAT

CCGCAAGCGGCAACCCTTCCAGGAGGGCTTTAGGATCACCTACGATGATCTGGAGGG TGGTAACA

TTCCCGCACTGTTGGATGTGGACGCCTACCAGGCGAGCTTGAAAGATGACACCGAAC AGGGCGGG

GGTGGCGCAGGCGGCAGCAACAGCAGTGGCAGCGGCGCGGAAGAGAACTCCAACGCG GCAGCCG

CGGCAATGCAGCCGGTGGAGGACATGAACGATCATGCCATTCGCGGCGACACCTTTG CCACACGG

GCTGAGGAGAAGCGCGCTGAGGCCGAAGCAGCGGCCGAAGCTGCCGCCCCCGCTGCG CAACCCG

AGGTCGAGAAGCCTCAGAAGAAACCGGTGATCAAACCCCTGACAGAGGACAGCAAGA AACGCAG

TTACAACCTAATAAGCAATGACAGCACCTTCACCCAGTACCGCAGCTGGTACCTTGC ATACAACTA

CGGCGACCCTCAGACCGGAATCCGCTCATGGACCCTGCTTTGCACTCCTGACGTAAC CTGCGGCTC

GGAGCAGGTCTACTGGTCGTTGCCAGACATGATGCAAGACCCCGTGACCTTCCGCTC CACGCGCCA

GATCAGCAACTTTCCGGTGGTGGGCGCCGAGCTGTTGCCCGTGCACTCCAAGAGCTT CTACAACGA

CCAGGCCGTCTACTCCCAACTCATCCGCCAGTTTACCTCTCTGACCCACGTGTTCAA TCGCTTTCCC

GAGAACCAGATTTTGGCGCGCCCGCCAGCCCCCACCATCACCACCGTCAGTGAAAAC GTTCCTGCT

CTCACAGATCACGGGACGCTACCGCTGCGCAACAGCATCGGAGGAGTCCAGCGAGTG ACCATTAC TGACGCCAGACGCCGCACCTGCCCCTACGTTTACAAGGCCCTGGGCATAGTCTCGCCGCG CGTCCT

ATCGAGCCGCACTTTTTGAGCAAGCATGTCCATCCTTATATCGCCCAGCAATAACAC AGGCTGGGG

CCTGCGCTTCCCAAGCAAGATGTTTGGCGGGGCCAAGAAGCGCTCCGACCAACACCC AGTGCGCG

TGCGCGGGCACTACCGCGCGCCCTGGGGCGCGCACAAACGCGGCCGCACTGGGCGCA CCACCGTC

GATGACGCCATCGACGCGGTGGTGGAGGAGGCGCGCAACTACACGCCCACGCCGCCA CCAGTGTC

CACAGTGGACGCGGCCATTCAGACCGTGGTGCGCGGAGCCCGGCGCTATGCTAAAAT GAAGAGAC

GGCGGAGGCGCGTAGCACGTCGCCACCGCCGCCGACCCGGCACTGCCGCCCAACGCG CGGCGGCG

GCCCTGCTTAACCGCGCACGTCGCACCGGCCGACGGGCGGCCATGCGGGCCGCTCGA AGGCTGGC

CGCGGGTATTGTCACTGTGCCCCCCAGGTCCAGGCGACGAGCGGCCGCCGCAGCAGC CGCGGCCA

TTAGTGCTATGACTCAGGGTCGCAGGGGCAACGTGTATTGGGTGCGCGACTCGGTTA GCGGCCTGC

GCGTGCCCGTGCGCACCCGCCCCCCGCGCAACTAGATTGCAAGAAAAAACTACTTAG ACTCGTACT

GTTGTATGTATCCAGCGGCGGCGGCGCGCAACGAAGCTATGTCCAAGCGCAAAATCA AAGAAGAG

ATGCTCCAGGTCATCGCGCCGGAGATCTATGGCCCCCCGAAGAAGGAAGAGCAGGAT TACAAGCC

CCGAAAGCTAAAGCGGGTCAAAAAGAAAAAGAAAGATGATGATGATGAACTTGACGA CGAGGTG

GAACTGCTGCACGCTACCGCGCCCAGGCGACGGGTACAGTGGAAAGGTCGACGCGTA AAACGTGT

TTTGCGACCCGGCACCACCGTAGTCTTTACGCCCGGTGAGCGCTCCACCCGCACCTA CAAGCGCGT

GTATGATGAGGTGTACGGCGACGAGGACCTGCTTGAGCAGGCCAACGAGCGCCTCGG GGAGTTTG

CCTACGGAAAGCGGCATAAGGACATGCTGGCGTTGCCGCTGGACGAGGGCAACCCAA CACCTAGC

CTAAAGCCCGTAACACTGCAGCAGGTGCTGCCCGCGCTTGCACCGTCCGAAGAAAAG CGCGGCCT

AAAGCGCGAGTCTGGTGACTTGGCACCCACCGTGCAGCTGATGGTACCCAAGCGCCA GCGACTGG

AAGATGTCTTGGAAAAAATGACCGTGGAACCTGGGCTGGAGCCCGAGGTCCGCGTGC GGCCAATC

AAGCAGGTGGCGCCGGGACTGGGCGTGCAGACCGTGGACGTTCAGATACCCACTACC AGTAGCAC

CAGTATTGCCACCGCCACAGAGGGCATGGAGACACAAACGTCCCCGGTTGCCTCAGC GGTGGCGG

ATGCCGCGGTGCAGGCGGTCGCTGCGGCCGCGTCCAAGACCTCTACGGAGGTGCAAA CGGACCCG

TGGATGTTTCGCGTTTCAGCCCCCCGGCGCCCGCGCCGTTCGAGGAAGTACGGCGCC GCCAGCGCG

CT ACTGCCCG A AT ATGCCCT AC ATCCTTCC ATTGCGCCT ACCCCCGGCT ATCGTGGCT AC ACCT ACC

GCCCCAGAAGACGAGCAACTACCCGACGCCGAACCACCACTGGAACCCGCCGCCGCC GTCGCCGT

CGCCAGCCCGTGCTGGCCCCGATTTCCGTGCGCAGGGTGGCTCGCGAAGGAGGCAGG ACCCTGGT

GCTGCCAACAGCGCGCTACCACCCCAGCATCGTTTAAAAGCCGGTCTTTGTGGTTCT TGCAGATAT

GGCCCTCACCTGCCGCCTCCGTTTCCCGGTGCCGGGATTCCGAGGAAGAATGCACCG TAGGAGGG

GCATGGCCGGCCACGGCCTGACGGGCGGCATGCGTCGTGCGCACCACCGGCGGCGGC GCGCGTCG

CACCGTCGCATGCGCGGCGGTATCCTGCCCCTCCTTATTCCACTGATCGCCGCGGCG ATTGGCGCC

GTGCCCGGAATTGCATCCGTGGCCTTGCAGGCGCAGAGACACTGATTAAAAACAAGT TGCATGTG

GAAAAATCAAAATAAAAAGTCTGGACTCTCACGCTCGCTTGGTCCTGTAACTATTTT GTAGAATGG

AAGACATCAACTTTGCGTCTCTGGCCCCGCGACACGGCTCGCGCCCGTTCATGGGAA ACTGGCAAG

ATATCGGCACCAGCAATATGAGCGGTGGCGCCTTCAGCTGGGGCTCGCTGTGGAGCG GCATTAAA

AATTTCGGTTCCACCGTTAAGAACTATGGCAGCAAGGCCTGGAACAGCAGCACAGGC CAGATGCT

GAGGGATAAGTTGAAAGAGCAAAATTTCCAACAAAAGGTGGTAGATGGCCTGGCCTC TGGCATTA

GCGGGGTGGTGGACCTGGCCAACCAGGCAGTGCAAAATAAGATTAACAGTAAGCTTG ATCCCCGC

CCTCCCGTAGAGGAGCCTCCACCGGCCGTGGAGACAGTGTCTCCAGAGGGGCGTGGC GAAAAGCG

TCCGCGCCCCGACAGGGAAGAAACTCTGGTGACGCAAATAGACGAGCCTCCCTCGTA CGAGGAGG

CACTAAAGCAAGGCCTGCCCACCACCCGTCCCATCGCGCCCATGGCTACCGGAGTGC TGGGCCAG

CACACACCCGTAACGCTGGACCTGCCTCCCCCCGCCGACACCCAGCAGAAACCTGTG CTGCCAGG

CCCGACCGCCGTTGTTGTAACCCGTCCTAGCCGCGCGTCCCTGCGCCGCGCCGCCAG CGGTCCGCG

ATCGTTGCGGCCCGTAGCCAGTGGCAACTGGCAAAGCACACTGAACAGCATCGTGGG TCTGGGGG

TGCAATCCCTGAAGCGCCGACGATGCTTCTGATAGCTAACGTGTCGTATGTGTGTCA TGTATGCGT

CCATGTCGCCGCCAGAGGAGCTGCTGAGCCGCCGCGCGCCCGCTTTCCAAGATGGCT ACCCCTTCG

ATGATGCCGCAGTGGTCTTACATGCACATCTCGGGCCAGGACGCCTCGGAGTACCTG AGCCCCGG

GCTGGTGCAGTTTGCCCGCGCCACCGAGACGTACTTCAGCCTGAATAACAAGTTTAG AAACCCCAC

GGTGGCGCCTACGCACGACGTGACCACAGACCGGTCCCAGCGTTTGACGCTGCGGTT CATCCCTGT

GGACCGTGAGGATACTGCGTACTCGTACAAGGCGCGGTTCACCCTAGCTGTGGGTGA TAACCGTGT

GCTGGACATGGCTTCCACGTACTTTGACATCCGCGGCGTGCTGGACAGGGGCCCTAC TTTTAAGCC

CTACTCTGGCACTGCCTACAACGCCCTGGCTCCCAAGGGTGCCCCAAATCCTTGCGA ATGGGATGA

AGCTGCTACTGCTCTTGAAATAAACCTAGAAGAAGAGGACGATGACAACGAAGACGA AGTAGAC

G AGC A AGCTG AGC AGC A A A A A ACTC ACGT ATTTGGGC AGGCGCCTT ATTCTGGT AT A A AT ATT AC

A A AGG AGGGT ATTC A A AT AGGTGTCG A AGGTC A A AC ACCT A A AT ATGCCG AT A A A AC ATTTC A AC

CTGAACCTCAAATAGGAGAATCTCAGTGGTACGAAACAGAAATTAATCATGCAGCTG GGAGAGTC

CTAAAAAAGACTACCCCAATGAAACCATGTTACGGTTCATATGCAAAACCCACAAAT GAAAATGG

AGGGCAAGGCATTCTTGTAAAGCAACAAAATGGAAAGCTAGAAAGTCAAGTGGAAAT GCAATTTT TCTCAACTACTGAGGCAGCCGCAGGCAATGGTGATAACTTGACTCCTAAAGTGGTATTGT ACAGTG

A AG ATGT AG AT AT AG A A ACCCC AG AC ACTC AT ATTTCTT AC ATGCCC ACT ATTA AGG A AGGT A ACT

C ACG AG A ACT A ATGGGCC A AC A ATCT ATGCCC A AC AGGCCT A ATT AC ATTGCTTTT AGGG AC A ATT

TTATTGGTCTAATGTATTACAACAGCACGGGTAATATGGGTGTTCTGGCGGGCCAAG CATCGCAGT

TGAATGCTGTTGTAGATTTGCAAGACAGAAACACAGAGCTTTCATACCAGCTTTTGC TTGATTCCA

TTGGTGATAGAACCAGGTACTTTTCTATGTGGAATCAGGCTGTTGACAGCTATGATC CAGATGTTA

GAATTATTGAAAATCATGGAACTGAAGATGAACTTCCAAATTACTGCTTTCCACTGG GAGGTGTGA

TTAATACAGAGACTCTTACCAAGGTAAAACCTAAAACAGGTCAGGAAAATGGATGGG AAAAAGAT

GCTACAGAATTTTCAGATAAAAATGAAATAAGAGTTGGAAATAATTTTGCCATGGAA ATCAATCT

AAATGCCAACCTGTGGAGAAATTTCCTGTACTCCAACATAGCGCTGTATTTGCCCGA CAAGCTAAA

GT AC AGTCCTTCC A ACGT A A A A ATTTCTG AT A ACCC A A AC ACCT ACG ACT AC ATG A AC A AGCG AGT

GGTGGCTCCCGGGCTAGTGGACTGCTACATTAACCTTGGAGCACGCTGGTCCCTTGA CTATATGGA

CAACGTCAACCCATTTAACCACCACCGCAATGCTGGCCTGCGCTACCGCTCAATGTT GCTGGGCAA

TGGTCGCTATGTGCCCTTCCACATCCAGGTGCCTCAGAAGTTCTTTGCCATTAAAAA CCTCCTTCTC

CTGCCGGGCTCATACACCTACGAGTGGAACTTCAGGAAGGATGTTAACATGGTTCTG CAGAGCTCC

CT AGG A A ATG ACCT A AGGGTTG ACGG AGCC AGC ATT A AGTTTG AT AGC ATTTGCCTTT ACGCC ACC

TTCTTCCCCATGGCCCACAACACCGCCTCCACGCTTGAGGCCATGCTTAGAAACGAC ACCAACGAC

C AGTCCTTT AACG ACT ATCTCTCCGCCGCC A AC ATGCTCT ACCCT AT ACCCGCC A ACGCT ACC A AC

GTGCCCATATCCATCCCCTCCCGCAACTGGGCGGCTTTCCGCGGCTGGGCCTTCACG CGCCTTAAG

ACT A AGG A A ACCCC ATC ACTGGGCTCGGGCT ACG ACCCTT ATT AC ACCT ACTCTGGCTCT AT ACCC

TACCTAGATGGAACCTTTTACCTCAACCACACCTTTAAGAAGGTGGCCATTACCTTT GACTCTTCTG

TCAGCTGGCCTGGCAATGACCGCCTGCTTACCCCCAACGAGTTTGAAATTAAGCGCT CAGTTGACG

GGGAGGGTTACAACGTTGCCCAGTGTAACATGACCAAAGACTGGTTCCTGGTACAAA TGCTAGCT

A ACT AT A AC ATTGGCT ACC AGGGCTTCT AT ATCCC AG AG AGCT AC A AGG ACCGC ATGT ACTCCTTC

TTTAGAAACTTCCAGCCCATGAGCCGTCAGGTGGTGGATGATACTAAATACAAGGAC TACCAACA

GGTGGGCATCCTACACCAACACAACAACTCTGGATTTGTTGGCTACCTTGCCCCCAC CATGCGCGA

AGG AC AGGCCT ACCCTGCT A ACTTCCCCT ATCCGCTT AT AGGC A AG ACCGC AGTTG AC AGC ATT AC

CCAGAAAAAGTTTCTTTGCGATCGCACCCTTTGGCGCATCCCATTCTCCAGTAACTT TATGTCCATG

GGCGCACTCACAGACCTGGGCCAAAACCTTCTCTACGCCAACTCCGCCCACGCGCTA GACATGACT

TTTGAGGTGGATCCCATGGACGAGCCCACCCTTCTTTATGTTTTGTTTGAAGTCTTT GACGTGGTCC

GTGTGCACCAGCCGCACCGCGGCGTCATCGAAACCGTGTACCTGCGCACGCCCTTCT CGGCCGGCA

ACGCCACAACATAAAGAAGCAAGCAACATCAACAACAGCTGCCGCCATGGGCTCCAG TGAGCAG

GAACTGAAAGCCATTGTCAAAGATCTTGGTTGTGGGCCATATTTTTTGGGCACCTAT GACAAGCGC

TTTCCAGGCTTTGTTTCTCCACACAAGCTCGCCTGCGCCATAGTCAATACGGCCGGT CGCGAGACT

GGGGGCGTACACTGGATGGCCTTTGCCTGGAACCCGCACTCAAAAACATGCTACCTC TTTGAGCCC

TTTGGCTTTTCTGACCAGCGACTCAAGCAGGTTTACCAGTTTGAGTACGAGTCACTC CTGCGCCGT

AGCGCCATTGCTTCTTCCCCCGACCGCTGTATAACGCTGGAAAAGTCCACCCAAAGC GTACAGGGG

CCCAACTCGGCCGCCTGTGGACTATTCTGCTGCATGTTTCTCCACGCCTTTGCCAAC TGGCCCCAAA

CTCCCATGGATCACAACCCCACCATGAACCTTATTACCGGGGTACCCAACTCCATGC TCAACAGTC

CCCAGGTACAGCCCACCCTGCGTCGCAACCAGGAACAGCTCTACAGCTTCCTGGAGC GCCACTCGC

CCTACTTCCGCAGCCACAGTGCGCAGATTAGGAGCGCCACTTCTTTTTGTCACTTGA AAAACATGT

AAAAATAATGTACTAGAGACACTTTCAATAAAGGCAAATGCTTTTATTTGTACACTC TCGGGTGAT

TATTTACCCCCACCCTTGCCGTCTGCGCCGTTTAAAAATCAAAGGGGTTCTGCCGCG CATCGCTAT

GCGCCACTGGCAGGGACACGTTGCGATACTGGTGTTTAGTGCTCCACTTAAACTCAG GCACAACCA

TCCGCGGCAGCTCGGTGAAGTTTTCACTCCACAGGCTGCGCACCATCACCAACGCGT TTAGCAGGT

CGGGCGCCGATATCTTGAAGTCGCAGTTGGGGCCTCCGCCCTGCGCGCGCGAGTTGC GATACACA

GGGTTGCAGCACTGGAACACTATCAGCGCCGGGTGGTGCACGCTGGCCAGCACGCTC TTGTCGGA

GATCAGATCCGCGTCCAGGTCCTCCGCGTTGCTCAGGGCGAACGGAGTCAACTTTGG TAGCTGCCT

TCCCAAAAAGGGCGCGTGCCCAGGCTTTGAGTTGCACTCGCACCGTAGTGGCATCAA AAGGTGAC

CGTGCCCGGTCTGGGCGTTAGGATACAGCGCCTGCATAAAAGCCTTGATCTGCTTAA AAGCCACCT

GAGCCTTTGCGCCTTCAGAGAAGAACATGCCGCAAGACTTGCCGGAAAACTGATTGG CCGGACAG

GCCGCGTCGTGCACGCAGCACCTTGCGTCGGTGTTGGAGATCTGCACCACATTTCGG CCCCACCGG

TTCTTCACGATCTTGGCCTTGCTAGACTGCTCCTTCAGCGCGCGCTGCCCGTTTTCG CTCGTCACAT

CC ATTTC A ATC ACGTGCTCCTT ATTT ATC AT A ATGCTTCCGTGT AG AC ACTT A AGCTCGCCTTCG AT

CTCAGCGCAGCGGTGCAGCCACAACGCGCAGCCCGTGGGCTCGTGATGCTTGTAGGT CACCTCTGC

AAACGACTGCAGGTACGCCTGCAGGAATCGCCCCATCATCGTCACAAAGGTCTTGTT GCTGGTGAA

GGTCAGCTGCAACCCGCGGTGCTCCTCGTTCAGCCAGGTCTTGCATACGGCCGCCAG AGCTTCCAC

TTGGTC AGGC AGT AGTTTG A AGTTCGCCTTT AG ATCGTT ATCC ACGTGGT ACTTGTCC ATC AGCGCG

CGCGCAGCCTCCATGCCCTTCTCCCACGCAGACACGATCGGCACACTCAGCGGGTTC ATCACCGTA ATTTCACTTTCCGCTTCGCTGGGCTCTTCCTCTTCCTCTTGCGTCCGCATACCACGCGCC ACTGGGT

CGTCTTCATTCAGCCGCCGCACTGTGCGCTTACCTCCTTTGCCATGCTTGATTAGCA CCGGTGGGTT

GCTGAAACCCACCATTTGTAGCGCCACATCTTCTCTTTCTTCCTCGCTGTCCACGAT TACTAATACG

ACTCACTATAGGTGTGGAATTTCACAGGAGGTACAGCTATGACCATGATTACGGATT CACTGGCCG

TCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTG CAGCACATC

CCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAAC AGTTGCGCA

GCCTGAATGGCGAATAGGTCGCGCCGCACCGCGTCCGCGCTCGGGGGTGGTTTCGCG CTGCTCCTC

TTCCCGACTGGCCATTTCCTTCTCCTATAGGCAGAAAAAGATCATGGAGTCAGTCGA GAAGAAGG

ACAGCCTAACCGCCCCCTCTGAGTTCGCCACCACCGCCTCCACCGATGCCGCCAACG CGCCTACCA

CCTTCCCCGTCGAGGCACCCCCGCTTGAGGAGGAGGAAGTGATTATCGAGCAGGACC CAGGTTTT

GTAAGCGAAGACGACGAGGACCGCTCAGTACCAACAGAGGATAAAAAGCAAGACCAG GACAACG

CAGAGGCAAACGAGGAACAAGTCGGGCGGGGGGACGAAAGGCATGGCGACTACCTAG ATGTGGG

AGACGACGTGCTGTTGAAGCATCTGCAGCGCCAGTGCGCCATTATCTGCGACGCGTT GCAAGAGC

GCAGCGATGTGCCCCTCGCCATAGCGGATGTCAGCCTTGCCTACGAACGCCACCTAT TCTCACCGC

GCGTACCCCCCAAACGCCAAGAAAACGGCACATGCGAGCCCAACCCGCGCCTCAACT TCTACCCC

GTATTTGCCGTGCCAGAGGTGCTTGCCACCTATCACATCTTTTTCCAAAACTGCAAG ATACCCCTAT

CCTGCCGTGCCAACCGCAGCCGAGCGGACAAGCAGCTGGCCTTGCGGCAGGGCGCTG TCATACCT

GATATCGCCTCGCTCAACGAAGTGCCAAAAATCTTTGAGGGTCTTGGACGCGACGAG AAGCGCGC

GGCAAACGCTCTGCAACAGGAAAACAGCGAAAATGAAAGTCACTCTGGAGTGTTGGT GGAACTCG

AGGGTGACAACGCGCGCCTAGCCGTACTAAAACGCAGCATCGAGGTCACCCACTTTG CCTACCCG

GCACTTAACCTACCCCCCAAGGTCATGAGCACAGTCATGAGTGAGCTGATCGTGCGC CGTGCGCA

GCCCCTGGAGAGGGATGCAAATTTGCAAGAACAAACAGAGGAGGGCCTACCCGCAGT TGGCGAC

GAGCAGCTAGCGCGCTGGCTTCAAACGCGCGAGCCTGCCGACTTGGAGGAGCGACGC AAACTAAT

GATGGCCGCAGTGCTCGTTACCGTGGAGCTTGAGTGCATGCAGCGGTTCTTTGCTGA CCCGGAGAT

GCAGCGCAAGCTAGAGGAAACATTGCACTACACCTTTCGACAGGGCTACGTACGCCA GGCCTGCA

AGATCTCCAACGTGGAGCTCTGCAACCTGGTCTCCTACCTTGGAATTTTGCACGAAA ACCGCCTTG

GGCAAAACGTGCTTCATTCCACGCTCAAGGGCGAGGCGCGCCGCGACTACGTCCGCG ACTGCGTTT

ACTTATTTCTATGCTACACCTGGCAGACGGCCATGGGCGTTTGGCAGCAGTGCTTGG AGGAGTGCA

ACCTCAAGGAGCTGCAGAAACTGCTAAAGCAAAACTTGAAGGACCTATGGACGGCCT TCAACGAG

CGCTCCGTGGCCGCGCACCTGGCGGACATCATTTTCCCCGAACGCCTGCTTAAAACC CTGCAACAG

GGTCTGCCAGACTTCACCAGTCAAAGCATGTTGCAGAACTTTAGGAACTTTATCCTA GAGCGCTCA

GGAATCTTGCCCGCCACCTGCTGTGCACTTCCTAGCGACTTTGTGCCCATTAAGTAC CGCGAATGC

CCTCCGCCGCTTTGGGGCCACTGCTACCTTCTGCAGCTAGCCAACTACCTTGCCTAC CACTCTGACA

TAATGGAAGACGTGAGCGGTGACGGTCTACTGGAGTGTCACTGTCGCTGCAACCTAT GCACCCCGC

ACCGCTCCCTGGTTTGCAATTCGCAGCTGCTTAACGAAAGTCAAATTATCGGTACCT TTGAGCTGC

AGGGTCCCTCGCCTGACGAAAAGTCCGCGGCTCCGGGGTTGAAACTCACTCCGGGGC TGTGGACG

TCGGCTT ACCTTCGC A A ATTTGT ACCTG AGG ACT ACC ACGCCC ACG AG ATT AGGTTCT ACG A AG AC

CAATCCCGCCCGCCTAATGCGGAGCTTACCGCCTGCGTCATTACCCAGGGCCACATT CTTGGCCAA

TTGCAAGCCATCAACAAAGCCCGCCAAGAGTTTCTGCTACGAAAGGGACGGGGGGTT TACTTGGA

CCCCCAGTCCGGCGAGGAGCTCAACCCAATCCCCCCGCCGCCGCAGCCCTATCAGCA GCAGCCGC

GGGCCCTTGCTTCCCAGGATGGCACCCAAAAAGAAGCTGCAGCTGCCGCCGCCACCC ACGGACGA

GGAGGAATACTGGGACAGTCAGGCAGAGGAGGTTTTGGACGAGGAGGAGGAGGACAT GATGGAA

GACTGGGAGAGCCTAGACGAGGAAGCTTCCGAGGTCGAAGAGGTGTCAGACGAAACA CCGTCAC

CCTCGGTCGCATTCCCCTCGCCGGCGCCCCAGAAATCGGCAACCGGTTCCAGCATGG CTACAACCT

CCGCTCCTCAGGCGCCGCCGGCACTGCCCGTTCGCCGACCCAACCGTAGATGGGACA CCACTGGA

ACCAGGGCCGGTAAGTCCAAGCAGCCGCCGCCGTTAGCCCAAGAGCAACAACAGCGC CAAGGCTA

CCGCTCATGGCGCGGGCACAAGAACGCCATAGTTGCTTGCTTGCAAGACTGTGGGGG CAACATCT

CCTTCGCCCGCCGCTTTCTTCTCT ACC ATC ACGGCGTGGCCTTCCCCCGT A AC ATCCTGC ATT ACT A

CCGTCATCTCTACAGCCCATACTGCACCGGCGGCAGCGGCAGCAACAGCAGCGGCCA CACAGAAG

CAAAGGCGACCGGATAGCAAGACTCTGACAAAGCCCAAGAAATCCACAGCGGCGGCA GCAGCAG

GAGGAGGAGCGCTGCGTCTGGCGCCCAACGAACCCGTATCGACCCGCGAGCTTAGAA ACAGGATT

TTTCCCACTCTGTATGCTATATTTCAACAGAGCAGGGGCCAAGAACAAGAGCTGAAA ATAAAAAA

CAGGTCTCTGCGATCCCTCACCCGCAGCTGCCTGTATCACAAAAGCGAAGATCAGCT TCGGCGCAC

GCTGGAAGACGCGGAGGCTCTCTTCAGTAAATACTGCGCGCTGACTCTTAAGGACTA GTTTCGCGC

CCTTTCTCAAATTTAAGCGCGAAAACTACGTCATCTCCAGCGGCCACACCCGGCGCC AGCACCTGT

TGTCAGCGCCATTATGAGCAAGGAAATTCCCACGCCCTACATGTGGAGTTACCAGCC ACAAATGG

GACTTGCGGCTGGAGCTGCCCAAGACTACTCAACCCGAATAAACTACATGAGCGCGG GACCCCAC

ATGATATCCCGGGTCAACGGAATACGCGCCCACCGAAACCGAATTCTCCTGGAACAG GCGGCTAT

T ACC ACC AC ACCTCGT A AT A ACCTT A ATCCCCGT AGTTGGCCCGCTGCCCTGGTGT ACC AGG A A AG TCCCGCTCCCACCACTGTGGTACTTCCCAGAGACGCCCAGGCCGAAGTTCAGATGACTAA CTCAGG

GGCGCAGCTTGCGGGCGGCTTTCGTCACAGGGTGCGGTCGCCCGGGCAGGGTATAAC TCACCTGA

CAATCAGAGGGCGAGGTATTCAGCTCAACGACGAGTCGGTGAGCTCCTCGCTTGGTC TCCGTCCGG

ACGGGACATTTCAGATCGGCGGCGCCGGCCGCTCTTCATTCACGCCTCGTCAGGCAA TCCTAACTC

TGCAGACCTCGTCCTCTGAGCCGCGCTCTGGAGGCATTGGAACTCTGCAATTTATTG AGGAGTTTG

TGCC ATCGGTCT ACTTT AACCCCTTCTCGGG ACCTCCCGGCC ACT ATCCGG ATC A ATTT ATTCCT A A

CTTTGACGCGGTAAAGGACTCGGCGGACGGCTACGACTGAATGTTAAGTGGAGAGGC AGAGCAAC

TGCGCCTGAAACACCTGGTCCACTGTCGCCGCCACAAGTGCTTTGCCCGCGACTCCG GTGAGTTTT

GCTACTTTGAATTGCCCGAGGATCATATCGAGGGCCCGGCGCACGGCGTCCGGCTTA CCGCCCAGG

GAGAGCTTGCCCGTAGCCTGATTCGGGAGTTTACCCAGCGCCCCCTGCTAGTTGAGC GGGACAGG

GGACCCTGTGTTCTCACTGTGATTTGCAACTGTCCTAACCCTGGATTACATCAAGAT CTTTGTTGCC

ATCTCTGTGCTGAGTATAATAAATACAGAAATTAAAATATACTGGGGCTCCTATCGC CATCCTGTA

A ACGCC ACCGTCTTC ACCCGCCC A AGC A A ACC A AGGCG A ACCTT ACCTGGT ACTTTT A AC ATCTCT

CCCTCTGTGATTTACAACAGTTTCAACCCAGACGGAGTGAGTCTACGAGAGAACCTC TCCGAGCTC

AGCTACTCCATCAGAAAAAACACCACCCTCCTTACCTGCCGGGAACGTACGAGTGCG TCACCGGC

CGCTGCACCACACCTACCGCCTGACCGTAAACCAGACTTTTTCCGGACAGACCTCAA TAACTCTGT

TTACCAGAACAGGAGGTGAGCTTAGAAAACCCTTAGGGTATTAGGCCAAAGGCGCAG CTACTGTG

GGGTTT ATG A AC A ATTC A AGC A ACTCT ACGGGCT ATTCT A ATTC AGGTTTCTCT AG A A ATGG ACGG

AATTATTACAGAGCAGCGCCTGCTAGAAAGACGCAGGGCAGCGGCCGAGCAACAGCG CATGAATC

AAGAGCTCCAAGACATGGTTAACTTGCACCAGTGCAAAAGGGGTATCTTTTGTCTGG TAAAGCAG

GCCAAAGTCACCTACGACAGTAATACCACCGGACACCGCCTTAGCTACAAGTTGCCA ACCAAGCG

TCAGAAATTGGTGGTCATGGTGGGAGAAAAGCCCATTACCATAACTCAGCACTCGGT AGAAACCG

AAGGCTGCATTCACTCACCTTGTCAAGGACCTGAGGATCTCTGCACCCTTATTAAGA CCCTGTGCG

GTCTC A A AG ATCTT ATTCCCTTT A ACT A AT A A A A A A A A AT A AT A A AGC ATC ACTT ACTT A A A ATC A

GTTAGCAAATTTCTGTCCAGTTTATTCAGCAGCACCTCCTTGCCCTCCTCCCAGCTC TGGTATTGCA

GCTTCCTCCTGGCTGCAAACTTTCTCCACAATCTAAATGGAATGTCAGTTTCCTCCT GTTCCTGTCC

ATCCGCACCCACTATCTTCATGTTGTTGCAGATGAAGCGCGCAAGACCGTCTGAAGA TACCTTCAA

CCCCGTGTATCCATATGACACGGAAACCGGTCCTCCAACTGTGCCTTTTCTTACTCC TCCCTTTGTA

TCCCCCAATGGGTTTCAAGAGAGTCCCCCTGGGGTACTCTCTTTGCGCCTATCCGAA CCTCTAGTTA

CCTCCAATGGCATGCTTGCGCTCAAAATGGGCAACGGCCTCTCTCTGGACGAGGCCG GCAACCTTA

CCTCCCAAAATGTAACCACTGTGAGCCCACCTCTCAAAAAAACCAAGTCAAACATAA ACCTGGAA

ATATCTGCACCCCTCACAGTTACCTCAGAAGCCCTAACTGTGGCTGCCGCCGCACCT CTAATGGTC

GCGGGCAACACACTCACCATGCAATCACAGGCCCCGCTAACCGTGCACGACTCCAAA CTTAGCAT

TGCCACCCAAGGACCCCTCACAGTGTCAGAAGGAAAGCTAGCCCTGCAAACATCAGG CCCCCTCA

CC ACC ACCG AT AGC AGT ACCCTT ACT ATC ACTGCCTC ACCCCCTCT A ACT ACTGCC ACTGGT AGCTT

GGGCATTGACTTGAAAGAGCCCATTTATACACAAAATGGAAAACTAGGACTAAAGTA CGGGGCTC

CTTTGCATGTAACAGACGACCTAAACACTTTGACCGTAGCAACTGGTCCAGGTGTGA CTATTAATA

ATACTTCCTTGCAAACTAAAGTTACTGGAGCCTTGGGTTTTGATTCACAAGGCAATA TGCAACTTA

ATGT AGC AGG AGG ACT A AGG ATTG ATTCTC A A A AC AG ACGCCTT AT ACTTG ATGTT AGTT ATCCGT

TTG ATGCTC A A A ACC A ACT A A ATCT A AG ACT AGG AC AGGGCCCTCTTTTT AT AA ACTC AGCCC AC A

ACTTGG AT ATT AACT AC A AC A A AGGCCTTT ACTTGTTT AC AGCTTC A A AC A ATTCC A A A A AGCTTG

AGGTTAACCTAAGCACTGCCAAGGGGTTGATGTTTGACGCTACAGCCATAGCCATTA ATGCAGGA

GATGGGCTTGAATTTGGTTCACCTAATGCACCAAACACAAATCCCCTCAAAACAAAA ATTGGCCAT

GGCCTAGAATTTGATTCAAACAAGGCTATGGTTCCTAAACTAGGAACTGGCCTTAGT TTTGACAGC

ACAGGTGCCATTACAGTAGGAAACAAAAATAATGATAAGCTAACTTTGTGGACCACA CCAGCTCC

ATCTCCTAACTGTAGACTAAATGCAGAGAAAGATGCTAAACTCACTTTGGTCTTAAC AAAATGTGG

CAGTCAAATACTTGCTACAGTTTCAGTTTTGGCTGTTAAAGGCAGTTTGGCTCCAAT ATCTGGAAC

AGTTCAAAGTGCTCATCTTATTATAAGATTTGACGAAAATGGAGTGCTACTAAACAA TTCCTTCCT

GGACCCAGAATATTGGAACTTTAGAAATGGAGATCTTACTGAAGGCACAGCCTATAC AAACGCTG

TTGG ATTT ATGCCT A ACCT ATC AGCTT ATCC A A A ATCTC ACGGT A A A ACTGCC A A A AGT A AC ATTG

TC AGTC A AGTTT ACTT A A ACGG AG AC A A A ACT A A ACCTGT A AC ACT A ACC ATT AC ACT A A ACGGT

ACACAGGAAACAGGAGACACAACTCCAAGTGCAT ACTCT ATGTCATTTTCATGGGACTGGTCTGGC

C AC A ACT AC ATT A ATG A A AT ATTTGCC AC ATCCTCTT AC ACTTTTTC AT AC ATTGCCC A AG A AT AAA

GAATCGTTTGTGTTATGTTTCAACGTGTTTATTTTTCAATTGCAGAAAATTTCGAAT CATTTTTCATT

C AGT AGT AT AGCCCC ACC ACC AC AT AGCTT AT AC AG ATC ACCGT ACCTT A ATC A A ACTC AC AG A AC

CCTAGTATTCAACCTGCCACCTCCCTCCCAACACACAGAGTACACAGTCCTTTCTCC CCGGCTGGC

CTT A A A A AGC ATC AT ATC ATGGGT A AC AG AC AT ATTCTT AGGTGTT AT ATTCC AC ACGGTTTCCTGT

CGAGCCAAACGCTCATCAGTGATATTAATAAACTCCCCGGGCAGCTCACTTAAGTTC ATGTCGCTG

TCCAGCTGCTGAGCCACAGGCTGCTGTCCAACTTGCGGTTGCTTAACGGGCGGCGAA GGAGAAGT CCACGCCTACATGGGGGTAGAGTCATAATCGTGCATCAGGATAGGGCGGTGGTGCTGCAG CAGCG

CGCGAATAAACTGCTGCCGCCGCCGCTCCGTCCTGCAGGAATACAACATGGCAGTGG TCTCCTCAG

CGATGATTCGCACCGCCCGCAGCATAAGGCGCCTTGTCCTCCGGGCACAGCAGCGCA CCCTGATCT

CACTTAAATCAGCACAGTAACTGCAGCACAGCACCACAATATTGTTCAAAATCCCAC AGTGCAAG

GCGCTGTATCCAAAGCTCATGGCGGGGACCACAGAACCCACGTGGCCATCATACCAC AAGCGCAG

GTAGATTAAGTGGCGACCCCTCATAAACACGCTGGACATAAACATTACCTCTTTTGG CATGTTGTA

ATTC ACC ACCTCCCGGT ACC AT AT A A ACCTCTG ATT A A AC ATGGCGCC ATCC ACC ACC ATCCT AAA

CCAGCTGGCCAAAACCTGCCCGCCGGCTATACACTGCAGGGAACCGGGACTGGAACA ATGACAGT

GGAGAGCCCAGGACTCGTAACCATGGATCATCATGCTCGTCATGATATCAATGTTGG CACAACAC

AGGCACACGTGCATACACTTCCTCAGGATTACAAGCTCCTCCCGCGTTAGAACCATA TCCCAGGGA

ACAACCCATTCCTGAATCAGCGTAAATCCCACACTGCAGGGAAGACCTCGCACGTAA CTCACGTTG

TGCATTGTCAAAGTGTTACATTCGGGCAGCAGCGGATGATCCTCCAGTATGGTAGCG CGGGTTTCT

GTCTCAAAAGGAGGTAGACGATCCCTACTGTACGGAGTGCGCCGAGACAACCGAGAT CGTGTTGG

TCGTAGTGTCATGCCAAATGGAACGCCGGACGTAGTCATATTTCCTGAAGCAAAACC AGGTGCGG

GCGTGACAAACAGATCTGCGTCTCCGGTCTCGCCGCTTAGATCGCTCTGTGTAGTAG TTGTAGTAT

ATCCACTCTCTCAAAGCATCCAGGCGCCCCCTGGCTTCGGGTTCTATGTAAACTCCT TCATGCGCCG

CTGCCCTGATAACATCCACCACCGCAGAATAAGCCACACCCAGCCAACCTACACATT CGTTCTGCG

AGTCACACACGGGAGGAGCGGGAAGAGCTGGAAGAACCATGTTTTTTTTTTTATTCC AAAAGATTA

TCCAAAACCTCAAAATGAAGATCTATTAAGTGAACGCGCTCCCCTCCGGTGGCGTGG TCAAACTCT

ACAGCCAAAGAACAGATAATGGCATTTGTAAGATGTTGCACAATGGCTTCCAAAAGG CAAACGGC

CCTCACGTCCAAGTGGACGTAAAGGCTAAACCCTTCAGGGTGAATCTCCTCTATAAA CATTCCAGC

ACCTTCAACCATGCCCAAATAATTCTCATCTCGCCACCTTCTCAATATATCTCTAAG CAAATCCCGA

ATATTAAGTCCGGCCATTGTAAAAATCTGCTCCAGAGCGCCCTCCACCTTCAGCCTC AAGCAGCGA

ATCATGATTGCAAAAATTCAGGTTCCTCACAGACCTGTATAAGATTCAAAAGCGGAA CATTAACA

AAAATACCGCGATCCCGTAGGTCCCTTCGCAGGGCCAGCTGAACATAATCGTGCAGG TCTGCACG

GACCAGCGCGGCCACTTCCCCGCCAGGAACCATGACAAAAGAACCCACACTGATTAT GACACGCA

TACTCGGAGCTATGCTAACCAGCGTAGCCCCGATGTAAGCTTGTTGCATGGGCGGCG ATATAAAAT

GCAAGGTGCTGCTCAAAAAATCAGGCAAAGCCTCGCGCAAAAAAGAAAGCACATCGT AGTCATGC

TCATGCAGATAAAGGCAGGTAAGCTCCGGAACCACCACAGAAAAAGACACCATTTTT CTCTCAAA

C ATGTCTGCGGGTTTCTGC AT A A AC AC A A A AT A A A AT A AC A A A A A A AC ATTT A A AC ATT AG A AGC

CTGTCTTACAACAGGAAAAACAACCCTTATAAGCATAAGACGGACTACGGCCATGCC GGCGTGAC

CGTAAAAAAACTGGTCACCGTGATTAAAAAGCACCACCGACAGCTCCTCGGTCATGT CCGGAGTC

ATAATGTAAGACTCGGTAAACACATCAGGTTGATTCACATCGGTCAGTGCTAAAAAG CGACCGAA

ATAGCCCGGGGGAATACATACCCGCAGGCGTAGAGACAACATTACAGCCCCCATAGG AGGTATAA

CAAAATTAATAGGAGAGAAAAACACATAAACACCTGAAAAACCCTCCTGCCTAGGCA AAATAGCA

CCCTCCCGCTCCAGAACAACATACAGCGCTTCCACAGCGGCAGCCATAACAGTCAGC CTTACCAGT

A A A A A AG A A A ACCT ATT A A A A A A AC ACC ACTCG AC ACGGC ACC AGCTC A ATC AGTC AC AGTGT A A

AAAAGGGCCAAGTGCAGAGCGAGTATATATAGGACTAAAAAATGACGTAACGGTTAA AGTCCAC

AAAAAACACCCAGAAAACCGCACGCGAACCTACGCCCAGAAACGAAAGCCAAAAAAC CCACAAC

TTCCTC A A ATCGTC ACTTCCGTTTTCCC ACGTT ACGTC ACTTCCC ATTTT AAG A A A ACT AC A ATTCC

C A AC AC AT AC A AGTT ACTCCGCCCT A A A ACCT ACGTC ACCCGCCCCGTTCCC ACGCCCCGCGCC AC

GTC AC A A ACTCC ACCCCCTC ATT ATC AT ATTGGCTTC A ATCC A A A AT A AGGT AT ATT ATTG ATG AT

GTTAATTAATTTAAATCCGCATGCGATATCGAGCTCTCCCGGGAATTCGGATCTGCG ACGCGAGGC

TGGATGGCCTTCCCCATTATGATTCTTCTCGCGTTTAAGGGCACCAATAACTGCCTT AAAAAAATT

ACGCCCCGCCCTGCCACTCATCGCAGTACTGTTGTAATTCATTAAGCATTCTGCCGA CATGGAAGC

CATCACAAACGGCATGATGAACCTGAATCGCCAGCGGCATCAGCACCTTGTCGCCTT GCGTATAAT

ATTTGCCCATGGTGAAAACGGGGGCGAAGAAGTTGTCCATATTGGCCACGTTTAAAT CAAAACTG

GTGAAACTCACCCAGGGATTGGCTGAGACGAAAAACATATTCTCAATAAACCCTTTA GGGAAATA

GGCCAGGTTTTCACCGTAACACGCCACATCTTGCGAATATATGTGTAGAAACTGCCG GAAATCGTC

GTGGTATTCACTCCAGAGCGATGAAAACGTTTCAGTTTGCTCATGGAAAACGGTGTA ACAAGGGT

GAACACTATCCCATATCACCAGCTCACCGTCTTTCATTGCCATACGGAATTCCGGAT GAGCATTCA

TCAGGCGGGCAAGAATGTGAATAAAGGCCGGATAAAACTTGTGCTTATTTTTCTTTA CGGTCTTTA

AAAAGGCCGTAATATCCAGCTGAACGGTCTGGTTATAGGTACATTGAGCAACTGACT GAAATGCC

TCAAAATGTTCTTTACGATGCCATTGGGATATATCAACGGTGGTATATCCAGTGATT TTTTTCTCCA

TTTT AGCTTCCTT AGCTCCTG A A A ATCTCG AT A ACTC A A A A A AT ACGCCCGGT AGTG ATCTT ATTTC

ATTATGGTGAAAGTTGGAACCTCTTACGTGCCGATCAACGTCTCATTTTCGCCAAAA GTTGGCCCA

GGGCTTCCCGGT ATC AACAGGG ACACCAGGATTT ATTT ATTCTGCGAAGTGATCTTCCGTCACAGG

TATTTATTCGCGATAAGCTCATGGAGCGGCGTAACCGTCGCACAGGAAGGACAGAGA AAGCGCGG

ATCTGGGAAGTGACGGACAGAACGGTCAGGACCTGGATTGGGGAGGCGGTTGCCGCC GCTGCTGC TGACGGTGTGACGTTCTCTGTTCCGGTCACACCACATACGTTCCGCCATTCCTATGCGAT GCACATG

CTGTATGCCGGTATACCGCTGAAAGTTCTGCAAAGCCTGATGGGACATAAGTCCATC AGTTCAACG

GAAGTCTACACGAAGGTTTTTGCGCTGGATGTGGCTGCCCGGCACCGGGTGCAGTTT GCGATGCCG

GAGTCTGATGCGGTTGCGATGCTGAAACAATTATCCTGAGAATAAATGCCTTGGCCT TTATATGGA

AATGTGGAACTGAGTGGATATGCTGTTTTTGTCTGTTAAACAGAGAAGCTGGCTGTT ATCCACTGA

GAAGCGAACGAAACAGTCGGGAAAATCTCCCATTATCGTAGAGATCCGCATTATTAA TCTCAGGA

GCCTGTGTAGCGTTTATAGGAAGTAGTGTTCTGTCATGATGCCTGCAAGCGGTAACG AAAACGATT

TGAATATGCCTTCAGGAACAATAGAAATCTTCGTGCGGTGTTACGTTGAAGTGGAGC GGATTATGT

CAGCAATGGACAGAACAACCTAATGAACACAGAACCATGATGTGGTCTGTCCTTTTA CAGCCAGT

AGTGCTCGCCGCAGTCGAGCGACAGGGCGAAGCCCTCGAGTGAGCGAGGAAGCACCA GGGAACA

GC ACTT AT AT ATTCTGCTT AC AC ACG ATGCCTG A A A A A ACTTCCCTTGGGGTT ATCC ACTT ATCC AC

GGGG AT ATTTTT AT A ATT ATTTTTTTT AT AGTTTTT AG ATCTTCTTTTTT AG AGCGCCTTGT AGGCCT

TTATCCATGCTGGTTCTAGAGAAGGTGTTGTGACAAATTGCCCTTTCAGTGTGACAA ATCACCCTC

AAATGACAGTCCTGTCTGTGACAAATTGCCCTTAACCCTGTGACAAATTGCCCTCAG AAGAAGCTG

_{TTTTTTCACAAAGTTATCCCTGCTTATTGACTCTTTTTTATTTAGTGTGACAATC TAAAAACTTGTCA}

CACTTCACATGGATCTGTCATGGCGGAAACAGCGGTTATCAATCACAAGAAACGTAA AAATAGCC

CGCGAATCGTCCAGTCAAACGACCTCACTGAGGCGGCATATAGTCTCTCCCGGGATC AAAAACGT

ATGCTGTATCTGTTCGTTGACCAGATCAGAAAATCTGATGGCACCCTACAGGAACAT GACGGTATC

TGCGAGATCCATGTTGCTAAATATGCTGAAATATTCGGATTGACCTCTGCGGAAGCC AGTAAGGAT

ATACGGCAGGCATTGAAGAGTTTCGCGGGGAAGGAAGTGGTTTTTTATCGCCCTGAA GAGGATGC

CGGCGATGAAAAAGGCTATGAATCTTTTCCTTGGTTTATCAAACGTGCGCACAGTCC ATCCAGAGG

GCTTT AC AGTGT AC AT ATC A ACCC AT ATCTC ATTCCCTTCTTT ATCGGGTT AC AG A ACCGGTTT ACG

CAGTTTCGGCTTAGTGAAACAAAAGAAATCACCAATCCGTATGCCATGCGTTTATAC GAATCCCTG

TGTCAGTATCGTAAGCCGGATGGCTCAGGCATCGTCTCTCTGAAAATCGACTGGATC ATAGAGCGT

TACCAGCTGCCTCAAAGTTACCAGCGTATGCCTGACTTCCGCCGCCGCTTCCTGCAG GTCTGTGTTA

ATGAGATCAACAGCAGAACTCCAATGCGCCTCTCATACATTGAGAAAAAGAAAGGCC GCCAGACG

ACTCATATCGTATTTTCCTTCCGCGATATCACTTCCATGACGACAGGATAGTCTGAG GGTTATCTGT

CACAGATTTGAGGGTGGTTCGTCACATTTGTTCTGACCTACTGAGGGTAATTTGTCA CAGTTTTGCT

GTTTCCTTCAGCCTGCATGGATTTTCTCATACTTTTTGAACTGTAATTTTTAAGGAA GCCAAATTTG

AGGGCAGTTTGTCACAGTTGATTTCCTTCTCTTTCCCTTCGTCATGTGACCTGATAT CGGGGGTTAG

TTCGTCATCATTGATGAGGGTTGATTATCACAGTTTATTACTCTGAATTGGCTATCC GCGTGTGTAC

CTCTACCTGGAGTTTTTCCCACGGTGGATATTTCTTCTTGCGCTGAGCGTAAGAGCT ATCTGACAGA

ACAGTTCTTCTTTGCTTCCTCGCCAGTTCGCTCGCTATGCTCGGTTACACGGCTGCG GCGAGCGCTA

GTGATAATAAGTGACTGAGGTATGTGCTCTTCTTATCTCCTTTTGTAGTGTTGCTCT TATTTTAAAC

AACTTTGCGGTTTTTTGATGACTTTGCGATTTTGTTGTTGCTTTGCAGTAAATTGCA AGATTTAATA

AAAAAACGCAAAGCAATGATTAAAGGATGTTCAGAATGAAACTCATGGAAACACTTA ACCAGTGC

ATAAACGCTGGTCATGAAATGACGAAGGCTATCGCCATTGCACAGTTTAATGATGAC AGCCCGGA

AGCGAGGAAAATAACCCGGCGCTGGAGAATAGGTGAAGCAGCGGATTTAGTTGGGGT TTCTTCTC

AGGCTATCAGAGATGCCGAGAAAGCAGGGCGACTACCGCACCCGGATATGGAAATTC GAGGACG

GGTTGAGCAACGTGTTGGTTATACAATTGAACAAATTAATCATATGCGTGATGTGTT TGGTACGCG

ATTGCGACGTGCTGAAGACGTATTTCCACCGGTGATCGGGGTTGCTGCCCATAAAGG TGGCGTTTA

CAAAACCTCAGTTTCTGTTCATCTTGCTCAGGATCTGGCTCTGAAGGGGCTACGTGT TTTGCTCGTG

GAAGGTAACGACCCCCAGGGAACAGCCTCAATGTATCACGGATGGGTACCAGATCTT CATATTCA

TGCAGAAGACACTCTCCTGCCTTTCTATCTTGGGGAAAAGGACGATGTCACTTATGC AATAAAGCC

CACTTGCTGGCCGGGGCTTGACATTATTCCTTCCTGTCTGGCTCTGCACCGTATTGA AACTGAGTTA

ATGGGCAAATTTGATGAAGGTAAACTGCCCACCGATCCACACCTGATGCTCCGACTG GCCATTGAA

ACTGTTGCTCATGACTATGATGTCATAGTTATTGACAGCGCGCCTAACCTGGGTATC GGCACGATT

AATGTCGTATGTGCTGCTGATGTGCTGATTGTTCCCACGCCTGCTGAGTTGTTTGAC TACACCTCCG

CACTGCAGTTTTTCGATATGCTTCGTGATCTGCTCAAGAACGTTGATCTTAAAGGGT TCGAGCCTG

ATGTACGTATTTTGCTTACCAAATACAGCAATAGTAATGGCTCTCAGTCCCCGTGGA TGGAGGAGC

AAATTCGGGATGCCTGGGGAAGCATGGTTCTAAAAAATGTTGTACGTGAAACGGATG AAGTTGGT

AAAGGTCAGATCCGGATGAGAACTGTTTTTGAACAGGCCATTGATCAACGCTCTTCA ACTGGTGCC

TGGAGAAATGCTCTTTCTATTTGGGAACCTGTCTGCAATGAAATTTTCGATCGTCTG ATTAAACCAC

GCTGGGAGATTAGATAATGAAGCGTGCGCCTGTTATTCCAAAACATACGCTCAATAC TCAACCGGT

TGAAGATACTTCGTTATCGACACCAGCTGCCCCGATGGTGGATTCGTTAATTGCGCG CGTAGGAGT

AATGGCTCGCGGTAATGCCATTACTTTGCCTGTATGTGGTCGGGATGTGAAGTTTAC TCTTGAAGT

GCTCCGGGGTGATAGTGTTGAGAAGACCTCTCGGGTATGGTCAGGTAATGAACGTGA CCAGGAGC

TGCTTACTGAGGACGCACTGGATGATCTCATCCCTTCTTTTCTACTGACTGGTCAAC AGACACCGG

CGTTCGGTCGAAGAGTATCTGGTGTCATAGAAATTGCCGATGGGAGTCGCCGTCGTA AAGCTGCTG CACTTACCGAAAGTGATTATCGTGTTCTGGTTGGCGAGCTGGATGATGAGCAGATGGCTG CATTAT

CCAGATTGGGTAACGATTATCGCCCAACAAGTGCTTATGAACGTGGTCAGCGTTATG CAAGCCGAT

TGCAGAATGAATTTGCTGGAAATATTTCTGCGCTGGCTGATGCGGAAAATATTTCAC GTAAGATTA

TTACCCGCTGTATCAACACCGCCAAATTGCCTAAATCAGTTGTTGCTCTTTTTTCTC ACCCCGGTGA

ACT ATCTGCCCGGTC AGGTG ATGC ACTTC A A A A AGCCTTT AC AG AT A A AG AGG A ATT ACTT AAGC A

GCAGGCATCTAACCTTCATGAGCAGAAAAAAGCTGGGGTGATATTTGAAGCTGAAGA AGTTATCA

CTCTTTTAACTTCTGTGCTTAAAACGTCATCTGCATCAAGAACTAGTTTAAGCTCAC GACATCAGTT

TGCTCCTGGAGCGACAGTATTGTATAAGGGCGATAAAATGGTGCTTAACCTGGACAG GTCTCGTGT

TCCAACTGAGTGTATAGAGAAAATTGAGGCCATTCTTAAGGAACTTGAAAAGCCAGC ACCCTGAT

GCGACCACGTTTTAGTCTACGTTTATCTGTCTTTACTTAATGTCCTTTGTTACAGGC CAGAAAGCAT

AACTGGCCTGAATATTCTCTCTGGGCCCACTGTTCCACTTGTATCGTCGGTCTGATA ATCAGACTGG

G ACC ACGGTCCC ACTCGT ATCGTCGGTCTG ATT ATT AGTCTGGG ACC ACGGTCCC ACTCGT ATCGT

CGGTCTGATTATTAGTCTGGGACCACGGTCCCACTCGTATCGTCGGTCTGATAATCA GACTGGGAC

CACGGTCCCACTCGTATCGTCGGTCTGATTATTAGTCTGGGACCATGGTCCCACTCG TATCGTCGGT

CTGATTATTAGTCTGGGACCACGGTCCCACTCGTATCGTCGGTCTGATTATTAGTCT GGAACCACG

GTCCCACTCGTATCGTCGGTCTGATTATTAGTCTGGGACCACGGTCCCACTCGTATC GTCGGTCTGA

TTATTAGTCTGGGACCACGATCCCACTCGTGTTGTCGGTCTGATTATCGGTCTGGGA CCACGGTCCC

ACTTGTATTGTCGATCAGACTATCAGCGTGAGACTACGATTCCATCAATGCCTGTCA AGGGCAAGT

ATTGACATGTCGTCGTAACCTGTAGAACGGAGTAACCTCGGTGTGCGGTTGTATGCC TGCTGTGGA

TTGCTGCTGTGTCCTGCTTATCCACAACATTTTGCGCACGGTTATGTGGACAAAATA CCTGGTTACC

CAGGCCGTGCCGGCACGTTAACCGGGCACATTTCCCCGAAAAGTGCCACCTGACGTC TAAGAAAC

C ATT ATT ATC ATG AC ATTA ACCT AT A A A A AT AGGCGT ATC ACG AGGCCCTTTCGTCTTC A AG A ATT

GG ATCCG A ATTCCCGGG AG AGCTCG AT ATCGC ATGCGG ATTT AA ATT A ATT A A

* C1F (SEQ ID NO: 87)

CATCATCAATAATATACCTTATTTTGGATTGAAGCCAATATGATAATGAGGGGGTGGAGT TTGTGA

CGTGGCGCGGGGCGTGGGAACGGGGCGGGTGACGTAGTAGTGTGGCGGAAGTGTGAT GTTGCAAG

TGTGGCGGAACACATGTAAGCGACGGATGTGGCAAAAGTGACGTTTTTGGTGTGCGC CGGTGTAC

ACAGGAAGTGACAATTTTCGCGCGGTTTTAGGCGGATGTTGTAGTAAATTTGGGCGT AACCGAGTA

AGATTTGGCCATTTTCGCGGGAAAACTGAATAAGAGGAAGTGAAATCTGAATAATTT TGTGTTACT

CATAGCGCGTAATATTTGTCTAGGGCCGCGGGGACTTTGACCGTTTACGTGGAGACT CGCCCAGGT

GTTTTTCTC AGGTGTTTTCCGCGTTCCGGGTC A A AGTTGGCGTTTT ATT ATT AT AGTC AGTCG A AGC

TTGGATCCGGTACCTCTAGAATTCTCGAGCGGCCGCTAGCGACATCGGATCTCCCGA TCCCCTATG

GTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGTATCTGCTCCC TGCTTGTGTG

TTGGAGGTCGCTGAGTAGTGCGCGAGCAAAATTTAAGCTACAACAAGGCAAGGCTTG ACCGACAA

TTGCATGAAGAATCTGCTTAGGGTTAGGCGTTTTGCGCTGCTTCGCGATGTACGGGC CAGATATAC

GCGTTG AC ATTG ATT ATTG ACT AGTT ATT AAT AGT A ATC A ATT ACGGGGTC ATT AGTTC AT AGCCC

ATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCC CAACGACCC

CCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTT CCATTGACG

TCAATGGGTGGACTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCA TATGCCAAG

TACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTA CATGACCTT

ATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGT GATGCGGTTT

TGGCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTC CACCCCATT

GACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGT AACAACTCC

GCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGA GCTCTCTG

GCT A ACT AG AG A ACCC ACTGCTT ACTGGCTT ATCGA A ATT AAT ACG ACTC ACT AT AGGG AG ACCC A

AGCTGGCT AGTT A AGCT ATC A AC A AGTTTGT AC A A A A A AGC AGGCTTT A A AGG A ACC A ATTC AGT

CGACTGGATCCGGTACCACCATGTTCCTGAACTGCTGCCCAGGTTGCTGTATGGAGC CTGAATTCA

CCATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGC TGGACGGC

GACGTAAACGGCCACAAGTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTAC GGCAAGCT

GACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTGCCCTGGCCCACCCTCGT GACCACCCT

GACCTGGGGCGTGCAGTGCTTCGCCCGCTACCCCGACCACATGAAGCAGCACGACTT CTTCAAGTC

CGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAA CTACAAGA

CCCGCGCCGAGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGG GCATCGAC

TTCAAGGAGGACGGCAACATCCTGGGGCACAAGCTGGAGTACAACGCCATCAGCGAC AACGTCTA

TATCACCGCCGACAAGCAGAAGAACGGCATCAAGGCCAACTTCAAGATCCGCCACAA CATCGAGG

ACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCC CCGTGCTG CTGCCCGACAACCACTACCTGAGCACCCAGTCCAAGCTGAGCAAAGACCCCAACGAGAAG CGCGA

TCACATGGTCCTGCTGGAGTTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGA GCTGTACAA

GGTCGACTATCCGTACGACGTACCAGACTACGCATAACCGCGGCCGCACTCGAGATA TCTAGACC

CAGCTTTCTTGTACAAAGTGGTTGATCTAGAGGGCCCGCGGTTCGAAGGTAAGCCTA TCCCTAACC

CTCTCCTCGGTCTCGATTCTACGCGTACCGGTTAGTAATGAGTTTAAACGGGGGAGG CTAACTGAA

ACACGGAAGGAGACAATACCGGAAGGAACCCGCGCTATGACGGCAATAAAAAGACAG AATAAAA

CGCACGGGTGTTGGGTCGTTTGTTCATAAACGCGGGGTTCGGTCCCAGGGCTGGCAC TCTGTCGAT

ACCCCACCGAGACCCCATTGGGGCCAATACGCCCGCGTTTCTTCCTTTTCCCCACCC CACCCCCCA

AGTTCGGGTGAAGGCCCAGGGCTCGCAGCCAACGTCGGGGCGGCAGGCCCTGCCATA GCAGATCC

GATTCGACAGATCACTGAAATGTGTGGGCGTGGCTTAAGGGTGGGAAAGAATATATA AGGTGGGG

GTCTTATGTAGTTTTGTATCTGTTTTGCAGCAGCCGCCGCCGCCATGAGCACCAACT CGTTTGATGG

AAGCATTGTGAGCTCATATTTGACAACGCGCATGCCCCCATGGGCCGGGGTGCGTCA GAATGTGAT

GGGCTCCAGCATTGATGGTCGCCCCGTCCTGCCCGCAAACTCTACTACCTTGACCTA CGAGACCGT

GTCTGGAACGCCGTTGGAGACTGCAGCCTCCGCCGCCGCTTCAGCCGCTGCAGCCAC CGCCCGCGG

GATTGTGACTGACTTTGCTTTCCTGAGCCCGCTTGCAAGCAGTGCAGCTTCCCGTTC ATCCGCCCGC

GATGACAAGTTGACGGCTCTTTTGGCACAATTGGATTCTTTGACCCGGGAACTTAAT GTCGTTTCTC

AGCAGCTGTTGGATCTGCGCCAGCAGGTTTCTGCCCTGAAGGCTTCCTCCCCTCCCA ATGCGGTTT

AAAACATAAATAAAAAACCAGACTCTGTTTGGATTTGGATCAAGCAAGTGTCTTGCT GTCTTTATT

TAGGGGTTTTGCGCGCGCGGTAGGCCCGGGACCAGCGGTCTCGGTCGTTGAGGGTCC TGTGTATTT

TTTCCAGGACGTGGTAAAGGTGACTCTGGATGTTCAGATACATGGGCATAAGCCCGT CTCTGGGGT

GGAGGTAGCACCACTGCAGAGCTTCATGCTGCGGGGTGGTGTTGTAGATGATCCAGT CGTAGCAG

GAGCGCTGGGCGTGGTGCCTAAAAATGTCTTTCAGTAGCAAGCTGATTGCCAGGGGC AGGCCCTT

GGTGTAAGTGTTTACAAAGCGGTTAAGCTGGGATGGGTGCATACGTGGGGATATGAG ATGCATCT

TGGACTGTATTTTTAGGTTGGCTATGTTCCCAGCCATATCCCTCCGGGGATTCATGT TGTGCAGAAC

CACCAGCACAGTGTATCCGGTGCACTTGGGAAATTTGTCATGTAGCTTAGAAGGAAA TGCGTGGA

AGAACTTGGAGACGCCCTTGTGACCTCCAAGATTTTCCATGCATTCGTCCATAATGA TGGCAATGG

GCCCACGGGCGGCGGCCTGGGCGAAGATATTTCTGGGATCACTAACGTCATAGTTGT GTTCCAGGA

TGAGATCGTCATAGGCCATTTTTACAAAGCGCGGGCGGAGGGTGCCAGACTGCGGTA TAATGGTT

CCATCCGGCCCAGGGGCGTAGTTACCCTCACAGATTTGCATTTCCCACGCTTTGAGT TCAGATGGG

GGGATCATGTCTACCTGCGGGGCGATGAAGAAAACGGTTTCCGGGGTAGGGGAGATC AGCTGGGA

AGAAAGCAGGTTCCTGAGCAGCTGCGACTTACCGCAGCCGGTGGGCCCGTAAATCAC ACCTATTA

CCGGCTGCAACTGGTAGTTAAGAGAGCTGCAGCTGCCGTCATCCCTGAGCAGGGGGG CCACTTCG

TTAAGCATGTCCCTGACTCGCATGTTTTCCCTGACCAAATCCGCCAGAAGGCGCTCG CCGCCCAGC

GATAGCAGTTCTTGCAAGGAAGCAAAGTTTTTCAACGGTTTGAGACCGTCCGCCGTA GGCATGCTT

TTGAGCGTTTGACCAAGCAGTTCCAGGCGGTCCCACAGCTCGGTCACCTGCTCTACG GCATCTCGA

TCCAGCATATCTCCTCGTTTCGCGGGTTGGGGCGGCTTTCGCTGTACGGCAGTAGTC GGTGCTCGTC

CAGACGGGCCAGGGTCATGTCTTTCCACGGGCGCAGGGTCCTCGTCAGCGTAGTCTG GGTCACGGT

GAAGGGGTGCGCTCCGGGCTGCGCGCTGGCCAGGGTGCGCTTGAGGCTGGTCCTGCT GGTGCTGA

AGCGCTGCCGGTCTTCGCCCTGCGCGTCGGCCAGGTAGCATTTGACCATGGTGTCAT AGTCCAGCC

CCTCCGCGGCGTGGCCCTTGGCGCGCAGCTTGCCCTTGGAGGAGGCGCCGCACGAGG GGCAGTGC

AGACTTTTGAGGGCGTAGAGCTTGGGCGCGAGAAATACCGATTCCGGGGAGTAGGCA TCCGCGCC

GCAGGCCCCGCAGACGGTCTCGCATTCCACGAGCCAGGTGAGCTCTGGCCGTTCGGG GTCAAAAA

CCAGGTTTCCCCCATGCTTTTTGATGCGTTTCTTACCTCTGGTTTCCATGAGCCGGT GTCCACGCTC

GGTGACGAAAAGGCTGTCCGTGTCCCCGTATACAGACTTGAGAGGCCTGTCCTCGAG CGGTGTTCC

GCGGTCCTCCTCGTATAGAAACTCGGACCACTCTGAGACAAAGGCTCGCGTCCAGGC CAGCACGA

AGGAGGCTAAGTGGGAGGGGTAGCGGTCGTTGTCCACTAGGGGGTCCACTCGCTCCA GGGTGTGA

AGACACATGTCGCCCTCTTCGGCATCAAGGAAGGTGATTGGTTTGTAGGTGTAGGCC ACGTGACCG

GGTGTTCCTGAAGGGGGGCTATAAAAGGGGGTGGGGGCGCGTTCGTCCTCACTCTCT TCCGCATCG

CTGTCTGCGAGGGCCAGCTGTTGGGGTGAGTACTCCCTCTGAAAAGCGGGCATGACT TCTGCGCTA

AGATTGTCAGTTTCCAAAAACGAGGAGGATTTGATATTCACCTGGCCCGCGGTGATG CCTTTGAGG

GTGGCCGCATCCATCTGGTCAGAAAAGACAATCTTTTTGTTGTCAAGCTTGGTGGCA AACGACCCG

TAGAGGGCGTTGGACAGCAACTTGGCGATGGAGCGCAGGGTTTGGTTTTTGTCGCGA TCGGCGCG

CTCCTTGGCCGCGATGTTTAGCTGCACGTATTCGCGCGCAACGCACCGCCATTCGGG AAAGACGGT

GGTGCGCTCGTCGGGCACCAGGTGCACGCGCCAACCGCGGTTGTGCAGGGTGACAAG GTCAACGC

TGGTGGCTACCTCTCCGCGTAGGCGCTCGTTGGTCCAGCAGAGGCGGCCGCCCTTGC GCGAGCAGA

ATGGCGGTAGGGGGTCTAGCTGCGTCTCGTCCGGGGGGTCTGCGTCCACGGTAAAGA CCCCGGGC

AGCAGGCGCGCGTCGAAGTAGTCTATCTTGCATCCTTGCAAGTCTAGCGCCTGCTGC CATGCGCGG

GCGGCAAGCGCGCGCTCGTATGGGTTGAGTGGGGGACCCCATGGCATGGGGTGGGTG AGCGCGGA

GGCGTACATGCCGCAAATGTCGTAAACGTAGAGGGGCTCTCTGAGTATTCCAAGATA TGTAGGGT AGCATCTTCCACCGCGGATGCTGGCGCGCACGTAATCGTATAGTTCGTGCGAGGGAGCGA GGAGG

TCGGGACCGAGGTTGCTACGGGCGGGCTGCTCTGCTCGGAAGACTATCTGCCTGAAG ATGGCATGT

GAGTTGGATGATATGGTTGGACGCTGGAAGACGTTGAAGCTGGCGTCTGTGAGACCT ACCGCGTC

ACGCACGAAGGAGGCGTAGGAGTCGCGCAGCTTGTTGACCAGCTCGGCGGTGACCTG CACGTCTA

GGGCGCAGTAGTCCAGGGTTTCCTTGATGATGTCATACTTATCCTGTCCCTTTTTTT TCCACAGCTC

GCGGTTGAGGACAAACTCTTCGCGGTCTTTCCAGTACTCTTGGATCGGAAACCCGTC GGCCTCCGA

ACGGTAAGAGCCTAGCATGTAGAACTGGTTGACGGCCTGGTAGGCGCAGCATCCCTT TTCTACGGG

TAGCGCGTATGCCTGCGCGGCCTTCCGGAGCGAGGTGTGGGTGAGCGCAAAGGTGTC CCTGACCA

TGACCAGCATGAAGGGCACGAGCTGCTTCCCAAAGGCCCCCATCCAAGTATAGGTCT CTACATCGT

AGGTGACAAAGAGACGCTCGGTGCGAGGATGCGAGCCGATCGGGAAGAACTGGATCT CCCGCCAC

CAATTGGAGGAGTGGCTATTGATGTGGTGAAAGTAGAAGTCCCTGCGACGGGCCGAA CACTCGTG

CTGGCTTTTGTAAAAACGTGCGCAGTACTGGCAGCGGTGCACGGGCTGTACATCCTG CACGAGGTT

GACCTGACGACCGCGCACAAGGAAGCAGAGTGGGAATTTGAGCCCCTCGCCTGGCGG GTTTGGCT

GGTGGTCTTCTACTTCGGCTGCTTGTCCTTGACCGTCTGGCTGCTCGAGGGGAGTTA CGGTGGATC

GGACCACCACGCCGCGCGAGCCCAAAGTCCAGATGTCCGCGCGCGGCGGTCGGAGCT TGATGACA

ACATCGCGCAGATGGGAGCTGTCCATGGTCTGGAGCTCCCGCGGCGTCAGGTCAGGC GGGAGCTC

CTGCAGGTTTACCTCGCATAGACGGGTCAGGGCGCGGGCTAGATCCAGGTGATACCT AATTTCCAG

GGGCTGGTTGGTGGCGGCGTCGATGGCTTGCAAGAGGCCGCATCCCCGCGGCGCGAC TACGGTAC

CGCGCGGCGGGCGGTGGGCCGCGGGGGTGTCCTTGGATGATGCATCTAAAAGCGGTG ACGCGGGC

GAGCCCCCGGAGGTAGGGGGGGCTCCGGACCCGCCGGGAGAGGGGGCAGGGGCACGT CGGCGCC

GCGCGCGGGCAGGAGCTGGTGCTGCGCGCGTAGGTTGCTGGCGAACGCGACGACGCG GCGGTTGA

TCTCCTGAATCTGGCGCCTCTGCGTGAAGACGACGGGCCCGGTGAGCTTGAACCTGA AAGAGAGT

TCGACAGAATCAATTTCGGTGTCGTTGACGGCGGCCTGGCGCAAAATCTCCTGCACG TCTCCTGAG

TTGTCTTGATAGGCGATCTCGGCCATGAACTGCTCGATCTCTTCCTCCTGGAGATCT CCGCGTCCGG

CTCGCTCCACGGTGGCGGCGAGGTCGTTGGAAATGCGGGCCATGAGCTGCGAGAAGG CGTTGAGG

CCTCCCTCGTTCCAGACGCGGCTGTAGACCACGCCCCCTTCGGCATCGCGGGCGCGC ATGACCACC

TGCGCGAGATTGAGCTCCACGTGCCGGGCGAAGACGGCGTAGTTTCGCAGGCGCTGA AAGAGGTA

GTTGAGGGTGGTGGCGGTGTGTTCTGCCACGAAGAAGTACATAACCCAGCGTCGCAA CGTGGATT

CGTTGATATCCCCCAAGGCCTCAAGGCGCTCCATGGCCTCGTAGAAGTCCACGGCGA AGTTGAAA

AACTGGGAGTTGCGCGCCGACACGGTTAACTCCTCCTCCAGAAGACGGATGAGCTCG GCGACAGT

GTCGCGCACCTCGCGCTCAAAGGCTACAGGGGCCTCTTCTTCTTCTTCAATCTCCTC TTCCATAAGG

GCCTCCCCTTCTTCTTCTTCTGGCGGCGGTGGGGGAGGGGGGACACGGCGGCGACGA CGGCGCAC

CGGGAGGCGGTCGACAAAGCGCTCGATCATCTCCCCGCGGCGACGGCGCATGGTCTC GGTGACGG

CGCGGCCGTTCTCGCGGGGGCGCAGTTGGAAGACGCCGCCCGTCATGTCCCGGTTAT GGGTTGGCG

GGGGGCTGCCATGCGGCAGGGATACGGCGCTAACGATGCATCTCAACAATTGTTGTG TAGGTACT

CCGCCGCCGAGGGACCTGAGCGAGTCCGCATCGACCGGATCGGAAAACCTCTCGAGA AAGGCGTC

TAACCAGTCACAGTCGCAAGGTAGGCTGAGCACCGTGGCGGGCGGCAGCGGGCGGCG GTCGGGGT

TGTTTCTGGCGGAGGTGCTGCTGATGATGTAATTAAAGTAGGCGGTCTTGAGACGGC GGATGGTCG

ACAGAAGCACCATGTCCTTGGGTCCGGCCTGCTGAATGCGCAGGCGGTCGGCCATGC CCCAGGCTT

CGTTTTGACATCGGCGCAGGTCTTTGTAGTAGTCTTGCATGAGCCTTTCTACCGGCA CTTCTTCTTC

TCCTTCCTCTTGTCCTGCATCTCTTGCATCTATCGCTGCGGCGGCGGCGGAGTTTGG CCGTAGGTGG

CGCCCTCTTCCTCCCATGCGTGTGACCCCGAAGCCCCTCATCGGCTGAAGCAGGGCT AGGTCGGCG

ACAACGCGCTCGGCTAATATGGCCTGCTGCACCTGCGTGAGGGTAGACTGGAAGTCA TCCATGTCC

ACAAAGCGGTGGTATGCGCCCGTGTTGATGGTGTAAGTGCAGTTGGCCATAACGGAC CAGTTAAC

GGTCTGGTGACCCGGCTGCGAGAGCTCGGTGTACCTGAGACGCGAGTAAGCCCTCGA GTCAAATA

CGTAGTCGTTGCAAGTCCGCACCAGGTACTGGTATCCCACCAAAAAGTGCGGCGGCG GCTGGCGG

TAGAGGGGCCAGCGTAGGGTGGCCGGGGCTCCGGGGGCGAGATCTTCCAACATAAGG CGATGATA

TCCGTAGATGTACCTGGACATCCAGGTGATGCCGGCGGCGGTGGTGGAGGCGCGCGG AAAGTCGC

GGACGCGGTTCCAGATGTTGCGCAGCGGCAAAAAGTGCTCCATGGTCGGGACGCTCT GGCCGGTC

AGGCGCGCGCAATCGTTGACGCTCTAGACCGTGCAAAAGGAGAGCCTGTAAGCGGGC ACTCTTCC

GTGGTCTGGTGGATAAATTCGCAAGGGTATCATGGCGGACGACCGGGGTTCGAGCCC CGTATCCG

GCCGTCCGCCGTGATCCATGCGGTTACCGCCCGCGTGTCGAACCCAGGTGTGCGACG TCAGACAAC

GGGGGAGTGCTCCTTTTGGCTTCCTTCCAGGCGCGGCGGCTGCTGCGCTAGCTTTTT TGGCCACTGG

CCGCGCGCAGCGTAAGCGGTTAGGCTGGAAAGCGAAAGCATTAAGTGGCTCGCTCCC TGTAGCCG

GAGGGTTATTTTCCAAGGGTTGAGTCGCGGGACCCCCGGTTCGAGTCTCGGACCGGC CGGACTGCG

GCGAACGGGGGTTTGCCTCCCCGTCATGCAAGACCCCGCTTGCAAATTCCTCCGGAA ACAGGGAC

GAGCCCCTTTTTTGCTTTTCCCAGATGCATCCGGTGCTGCGGCAGATGCGCCCCCCT CCTCAGCAGC

GGCAAGAGCAAGAGCAGCGGCAGACATGCAGGGCACCCTCCCCTCCTCCTACCGCGT CAGGAGGG

GCGACATCCGCGGTTGACGCGGCAGCAGATGGTGATTACGAACCCCCGCGGCGCCGG GCCCGGCA CTACCTGGACTTGGAGGAGGGCGAGGGCCTGGCGCGGCTAGGAGCGCCCTCTCCTGAGCG GCACC

CAAGGGTGCAGCTGAAGCGTGATACGCGTGAGGCGTACGTGCCGCGGCAGAACCTGT TTCGCGAC

CGCGAGGGAGAGGAGCCCGAGGAGATGCGGGATCGAAAGTTCCACGCAGGGCGCGAG CTGCGGC

ATGGCCTGAATCGCGAGCGGTTGCTGCGCGAGGAGGACTTTGAGCCCGACGCGCGAA CCGGGATT

AGTCCCGCGCGCGCACACGTGGCGGCCGCCGACCTGGTAACCGCATACGAGCAGACG GTGAACCA

GGAGATTAACTTTCAAAAAAGCTTTAACAACCACGTGCGTACGCTTGTGGCGCGCGA GGAGGTGG

CTATAGGACTGATGCATCTGTGGGACTTTGTAAGCGCGCTGGAGCAAAACCCAAATA GCAAGCCG

CTCATGGCGCAGCTGTTCCTTATAGTGCAGCACAGCAGGGACAACGAGGCATTCAGG GATGCGCT

GCTAAACATAGTAGAGCCCGAGGGCCGCTGGCTGCTCGATTTGATAAACATCCTGCA GAGCATAG

TGGTGCAGGAGCGCAGCTTGAGCCTGGCTGACAAGGTGGCCGCCATCAACTATTCCA TGCTTAGCC

TGGGCAAGTTTTACGCCCGCAAGATATACCATACCCCTTACGTTCCCATAGACAAGG AGGTAAAG

ATCGAGGGGTTCTACATGCGCATGGCGCTGAAGGTGCTTACCTTGAGCGACGACCTG GGCGTTTAT

CGCAACGAGCGCATCCACAAGGCCGTGAGCGTGAGCCGGCGGCGCGAGCTCAGCGAC CGCGAGCT

GATGCACAGCCTGCAAAGGGCCCTGGCTGGCACGGGCAGCGGCGATAGAGAGGCCGA GTCCTACT

TTGACGCGGGCGCTGACCTGCGCTGGGCCCCAAGCCGACGCGCCCTGGAGGCAGCTG GGGCCGGA

CCTGGGCTGGCGGTGGCACCCGCGCGCGCTGGCAACGTCGGCGGCGTGGAGGAATAT GACGAGGA

CGATGAGTACGAGCCAGAGGACGGCGAGTACTAAGCGGTGATGTTTCTGATCAGATG ATGCAAGA

CGCAACGGACCCGGCGGTGCGGGCGGCGCTGCAGAGCCAGCCGTCCGGCCTTAACTC CACGGACG

ACTGGCGCCAGGTCATGGACCGCATCATGTCGCTGACTGCGCGCAATCCTGACGCGT TCCGGCAGC

AGCCGCAGGCCAACCGGCTCTCCGCAATTCTGGAAGCGGTGGTCCCGGCGCGCGCAA ACCCCACG

CACGAGAAGGTGCTGGCGATCGTAAACGCGCTGGCCGAAAACAGGGCCATCCGGCCC GACGAGG

CCGGCCTGGTCTACGACGCGCTGCTTCAGCGCGTGGCTCGTTACAACAGCGGCAACG TGCAGACC

AACCTGGACCGGCTGGTGGGGGATGTGCGCGAGGCCGTGGCGCAGCGTGAGCGCGCG CAGCAGC

AGGGCAACCTGGGCTCCATGGTTGCACTAAACGCCTTCCTGAGTACACAGCCCGCCA ACGTGCCGC

GGGGACAGGAGGACTACACCAACTTTGTGAGCGCACTGCGGCTAATGGTGACTGAGA CACCGCAA

AGTGAGGTGTACCAGTCTGGGCCAGACTATTTTTTCCAGACCAGTAGACAAGGCCTG CAGACCGTA

AACCTGAGCCAGGCTTTCAAAAACTTGCAGGGGCTGTGGGGGGTGCGGGCTCCCACA GGCGACCG

CGCGACCGTGTCTAGCTTGCTGACGCCCAACTCGCGCCTGTTGCTGCTGCTAATAGC GCCCTTCAC

GGACAGTGGCAGCGTGTCCCGGGACACATACCTAGGTCACTTGCTGACACTGTACCG CGAGGCCA

TAGGTCAGGCGCATGTGGACGAGCATACTTTCCAGGAGATTACAAGTGTCAGCCGCG CGCTGGGG

CAGGAGGACACGGGCAGCCTGGAGGCAACCCTAAACTACCTGCTGACCAACCGGCGG CAGAAGA

TCCCCTCGTTGCACAGTTTAAACAGCGAGGAGGAGCGCATTTTGCGCTACGTGCAGC AGAGCGTG

AGCCTTAACCTGATGCGCGACGGGGTAACGCCCAGCGTGGCGCTGGACATGACCGCG CGCAACAT

GGAACCGGGCATGTATGCCTCAAACCGGCCGTTTATCAACCGCCTAATGGACTACTT GCATCGCGC

GGCCGCCGTGAACCCCGAGTATTTCACCAATGCCATCTTGAACCCGCACTGGCTACC GCCCCCTGG

TTTCTACACCGGGGGATTCGAGGTGCCCGAGGGTAACGATGGATTCCTCTGGGACGA CATAGACG

ACAGCGTGTTTTCCCCGCAACCGCAGACCCTGCTAGAGTTGCAACAGCGCGAGCAGG CAGAGGCG

GCGCTGCGAAAGGAAAGCTTCCGCAGGCCAAGCAGCTTGTCCGATCTAGGCGCTGCG GCCCCGCG

GTC AG ATGCT AGT AGCCC ATTTCC A AGCTTG AT AGGGTCTCTT ACC AGC ACTCGC ACC ACCCGCCC

GCGCCTGCTGGGCGAGGAGGAGTACCTAAACAACTCGCTGCTGCAGCCGCAGCGCGA AAAAAACC

TGCCTCCGGCATTTCCCAACAACGGGATAGAGAGCCTAGTGGACAAGATGAGTAGAT GGAAGACG

TACGCGCAGGAGCACAGGGACGTGCCAGGCCCGCGCCCGCCCACCCGTCGTCAAAGG CACGACCG

TCAGCGGGGTCTGGTGTGGGAGGACGATGACTCGGCAGACGACAGCAGCGTCCTGGA TTTGGGAG

GGAGTGGCAACCCGTTTGCGCACCTTCGCCCCAGGCTGGGGAGAATGTTTTAAAAAA AAAAAAAG

CATGATGCAAAATAAAAAACTCACCAAGGCCATGGCACCGAGCGTTGGTTTTCTTGT ATTCCCCTT

AGTATGCGGCGCGCGGCGATGTATGAGGAAGGTCCTCCTCCCTCCTACGAGAGTGTG GTGAGCGC

GGCGCCAGTGGCGGCGGCGCTGGGTTCTCCCTTCGATGCTCCCCTGGACCCGCCGTT TGTGCCTCC

GCGGTACCTGCGGCCTACCGGGGGGAGAAACAGCATCCGTTACTCTGAGTTGGCACC CCTATTCGA

CACCACCCGTGTGTACCTGGTGGACAACAAGTCAACGGATGTGGCATCCCTGAACTA CCAGAACG

ACCACAGCAACTTTCTGACCACGGTCATTCAAAACAATGACTACAGCCCGGGGGAGG CAAGCACA

CAGACCATCAATCTTGACGACCGGTCGCACTGGGGCGGCGACCTGAAAACCATCCTG CATACCAA

CATGCCAAATGTGAACGAGTTCATGTTTACCAATAAGTTTAAGGCGCGGGTGATGGT GTCGCGCTT

GCCTACTAAGGACAATCAGGTGGAGCTGAAATACGAGTGGGTGGAGTTCACGCTGCC CGAGGGCA

ACTACTCCGAGACCATGACCATAGACCTTATGAACAACGCGATCGTGGAGCACTACT TGAAAGTG

GGCAGACAGAACGGGGTTCTGGAAAGCGACATCGGGGTAAAGTTTGACACCCGCAAC TTCAGACT

GGGGTTTGACCCCGTCACTGGTCTTGTCATGCCTGGGGTATATACAAACGAAGCCTT CCATCCAGA

CATCATTTTGCTGCCAGGATGCGGGGTGGACTTCACCCACAGCCGCCTGAGCAACTT GTTGGGCAT

CCGCAAGCGGCAACCCTTCCAGGAGGGCTTTAGGATCACCTACGATGATCTGGAGGG TGGTAACA

TTCCCGCACTGTTGGATGTGGACGCCTACCAGGCGAGCTTGAAAGATGACACCGAAC AGGGCGGG GGTGGCGCAGGCGGCAGCAACAGCAGTGGCAGCGGCGCGGAAGAGAACTCCAACGCGGCA GCCG

CGGCAATGCAGCCGGTGGAGGACATGAACGATCATGCCATTCGCGGCGACACCTTTG CCACACGG

GCTGAGGAGAAGCGCGCTGAGGCCGAAGCAGCGGCCGAAGCTGCCGCCCCCGCTGCG CAACCCG

AGGTCGAGAAGCCTCAGAAGAAACCGGTGATCAAACCCCTGACAGAGGACAGCAAGA AACGCAG

TTACAACCTAATAAGCAATGACAGCACCTTCACCCAGTACCGCAGCTGGTACCTTGC ATACAACTA

CGGCGACCCTCAGACCGGAATCCGCTCATGGACCCTGCTTTGCACTCCTGACGTAAC CTGCGGCTC

GGAGCAGGTCTACTGGTCGTTGCCAGACATGATGCAAGACCCCGTGACCTTCCGCTC CACGCGCCA

GATCAGCAACTTTCCGGTGGTGGGCGCCGAGCTGTTGCCCGTGCACTCCAAGAGCTT CTACAACGA

CCAGGCCGTCTACTCCCAACTCATCCGCCAGTTTACCTCTCTGACCCACGTGTTCAA TCGCTTTCCC

GAGAACCAGATTTTGGCGCGCCCGCCAGCCCCCACCATCACCACCGTCAGTGAAAAC GTTCCTGCT

CTCACAGATCACGGGACGCTACCGCTGCGCAACAGCATCGGAGGAGTCCAGCGAGTG ACCATTAC

TGACGCCAGACGCCGCACCTGCCCCTACGTTTACAAGGCCCTGGGCATAGTCTCGCC GCGCGTCCT

ATCGAGCCGCACTTTTTGAGCAAGCATGTCCATCCTTATATCGCCCAGCAATAACAC AGGCTGGGG

CCTGCGCTTCCCAAGCAAGATGTTTGGCGGGGCCAAGAAGCGCTCCGACCAACACCC AGTGCGCG

TGCGCGGGCACTACCGCGCGCCCTGGGGCGCGCACAAACGCGGCCGCACTGGGCGCA CCACCGTC

GATGACGCCATCGACGCGGTGGTGGAGGAGGCGCGCAACTACACGCCCACGCCGCCA CCAGTGTC

CACAGTGGACGCGGCCATTCAGACCGTGGTGCGCGGAGCCCGGCGCTATGCTAAAAT GAAGAGAC

GGCGGAGGCGCGTAGCACGTCGCCACCGCCGCCGACCCGGCACTGCCGCCCAACGCG CGGCGGCG

GCCCTGCTTAACCGCGCACGTCGCACCGGCCGACGGGCGGCCATGCGGGCCGCTCGA AGGCTGGC

CGCGGGTATTGTCACTGTGCCCCCCAGGTCCAGGCGACGAGCGGCCGCCGCAGCAGC CGCGGCCA

TTAGTGCTATGACTCAGGGTCGCAGGGGCAACGTGTATTGGGTGCGCGACTCGGTTA GCGGCCTGC

GCGTGCCCGTGCGCACCCGCCCCCCGCGCAACTAGATTGCAAGAAAAAACTACTTAG ACTCGTACT

GTTGTATGTATCCAGCGGCGGCGGCGCGCAACGAAGCTATGTCCAAGCGCAAAATCA AAGAAGAG

ATGCTCCAGGTCATCGCGCCGGAGATCTATGGCCCCCCGAAGAAGGAAGAGCAGGAT TACAAGCC

CCGAAAGCTAAAGCGGGTCAAAAAGAAAAAGAAAGATGATGATGATGAACTTGACGA CGAGGTG

GAACTGCTGCACGCTACCGCGCCCAGGCGACGGGTACAGTGGAAAGGTCGACGCGTA AAACGTGT

TTTGCGACCCGGCACCACCGTAGTCTTTACGCCCGGTGAGCGCTCCACCCGCACCTA CAAGCGCGT

GTATGATGAGGTGTACGGCGACGAGGACCTGCTTGAGCAGGCCAACGAGCGCCTCGG GGAGTTTG

CCTACGGAAAGCGGCATAAGGACATGCTGGCGTTGCCGCTGGACGAGGGCAACCCAA CACCTAGC

CTAAAGCCCGTAACACTGCAGCAGGTGCTGCCCGCGCTTGCACCGTCCGAAGAAAAG CGCGGCCT

AAAGCGCGAGTCTGGTGACTTGGCACCCACCGTGCAGCTGATGGTACCCAAGCGCCA GCGACTGG

AAGATGTCTTGGAAAAAATGACCGTGGAACCTGGGCTGGAGCCCGAGGTCCGCGTGC GGCCAATC

AAGCAGGTGGCGCCGGGACTGGGCGTGCAGACCGTGGACGTTCAGATACCCACTACC AGTAGCAC

CAGTATTGCCACCGCCACAGAGGGCATGGAGACACAAACGTCCCCGGTTGCCTCAGC GGTGGCGG

ATGCCGCGGTGCAGGCGGTCGCTGCGGCCGCGTCCAAGACCTCTACGGAGGTGCAAA CGGACCCG

TGGATGTTTCGCGTTTCAGCCCCCCGGCGCCCGCGCCGTTCGAGGAAGTACGGCGCC GCCAGCGCG

CT ACTGCCCG A AT ATGCCCT AC ATCCTTCC ATTGCGCCT ACCCCCGGCT ATCGTGGCT AC ACCT ACC

GCCCCAGAAGACGAGCAACTACCCGACGCCGAACCACCACTGGAACCCGCCGCCGCC GTCGCCGT

CGCCAGCCCGTGCTGGCCCCGATTTCCGTGCGCAGGGTGGCTCGCGAAGGAGGCAGG ACCCTGGT

GCTGCCAACAGCGCGCTACCACCCCAGCATCGTTTAAAAGCCGGTCTTTGTGGTTCT TGCAGATAT

GGCCCTCACCTGCCGCCTCCGTTTCCCGGTGCCGGGATTCCGAGGAAGAATGCACCG TAGGAGGG

GCATGGCCGGCCACGGCCTGACGGGCGGCATGCGTCGTGCGCACCACCGGCGGCGGC GCGCGTCG

CACCGTCGCATGCGCGGCGGTATCCTGCCCCTCCTTATTCCACTGATCGCCGCGGCG ATTGGCGCC

GTGCCCGGAATTGCATCCGTGGCCTTGCAGGCGCAGAGACACTGATTAAAAACAAGT TGCATGTG

GAAAAATCAAAATAAAAAGTCTGGACTCTCACGCTCGCTTGGTCCTGTAACTATTTT GTAGAATGG

AAGACATCAACTTTGCGTCTCTGGCCCCGCGACACGGCTCGCGCCCGTTCATGGGAA ACTGGCAAG

ATATCGGCACCAGCAATATGAGCGGTGGCGCCTTCAGCTGGGGCTCGCTGTGGAGCG GCATTAAA

AATTTCGGTTCCACCGTTAAGAACTATGGCAGCAAGGCCTGGAACAGCAGCACAGGC CAGATGCT

GAGGGATAAGTTGAAAGAGCAAAATTTCCAACAAAAGGTGGTAGATGGCCTGGCCTC TGGCATTA

GCGGGGTGGTGGACCTGGCCAACCAGGCAGTGCAAAATAAGATTAACAGTAAGCTTG ATCCCCGC

CCTCCCGTAGAGGAGCCTCCACCGGCCGTGGAGACAGTGTCTCCAGAGGGGCGTGGC GAAAAGCG

TCCGCGCCCCGACAGGGAAGAAACTCTGGTGACGCAAATAGACGAGCCTCCCTCGTA CGAGGAGG

CACTAAAGCAAGGCCTGCCCACCACCCGTCCCATCGCGCCCATGGCTACCGGAGTGC TGGGCCAG

CACACACCCGTAACGCTGGACCTGCCTCCCCCCGCCGACACCCAGCAGAAACCTGTG CTGCCAGG

CCCGACCGCCGTTGTTGTAACCCGTCCTAGCCGCGCGTCCCTGCGCCGCGCCGCCAG CGGTCCGCG

ATCGTTGCGGCCCGTAGCCAGTGGCAACTGGCAAAGCACACTGAACAGCATCGTGGG TCTGGGGG

TGCAATCCCTGAAGCGCCGACGATGCTTCTGATAGCTAACGTGTCGTATGTGTGTCA TGTATGCGT

CCATGTCGCCGCCAGAGGAGCTGCTGAGCCGCCGCGCGCCCGCTTTCCAAGATGGCT ACCCCTTCG

ATGATGCCGCAGTGGTCTTACATGCACATCTCGGGCCAGGACGCCTCGGAGTACCTG AGCCCCGG GCTGGTGCAGTTTGCCCGCGCCACCGAGACGTACTTCAGCCTGAATAACAAGTTTAGAAA CCCCAC

GGTGGCGCCTACGCACGACGTGACCACAGACCGGTCCCAGCGTTTGACGCTGCGGTT CATCCCTGT

GGACCGTGAGGATACTGCGTACTCGTACAAGGCGCGGTTCACCCTAGCTGTGGGTGA TAACCGTGT

GCTGGACATGGCTTCCACGTACTTTGACATCCGCGGCGTGCTGGACAGGGGCCCTAC TTTTAAGCC

CTACTCTGGCACTGCCTACAACGCCCTGGCTCCCAAGGGTGCCCCAAATCCTTGCGA ATGGGATGA

AGCTGCTACTGCTCTTGAAATAAACCTAGAAGAAGAGGACGATGACAACGAAGACGA AGTAGAC

G AGC A AGCTG AGC AGC A A A A A ACTC ACGT ATTTGGGC AGGCGCCTT ATTCTGGT AT A A AT ATT AC

A A AGG AGGGT ATTC A A AT AGGTGTCG A AGGTC A A AC ACCT A A AT ATGCCG AT A A A AC ATTTC A AC

CTGAACCTCAAATAGGAGAATCTCAGTGGTACGAAACAGAAATTAATCATGCAGCTG GGAGAGTC

CTAAAAAAGACTACCCCAATGAAACCATGTTACGGTTCATATGCAAAACCCACAAAT GAAAATGG

AGGGCAAGGCATTCTTGTAAAGCAACAAAATGGAAAGCTAGAAAGTCAAGTGGAAAT GCAATTTT

TCTCAACTACTGAGGCAGCCGCAGGCAATGGTGATAACTTGACTCCTAAAGTGGTAT TGTACAGTG

A AG ATGT AG AT AT AG A A ACCCC AG AC ACTC AT ATTTCTT AC ATGCCC ACT ATTA AGG A AGGT A ACT

C ACG AG A ACT A ATGGGCC A AC A ATCT ATGCCC A AC AGGCCT A ATT AC ATTGCTTTT AGGG AC A ATT

TTATTGGTCTAATGTATTACAACAGCACGGGTAATATGGGTGTTCTGGCGGGCCAAG CATCGCAGT

TGAATGCTGTTGTAGATTTGCAAGACAGAAACACAGAGCTTTCATACCAGCTTTTGC TTGATTCCA

TTGGTGATAGAACCAGGTACTTTTCTATGTGGAATCAGGCTGTTGACAGCTATGATC CAGATGTTA

GAATTATTGAAAATCATGGAACTGAAGATGAACTTCCAAATTACTGCTTTCCACTGG GAGGTGTGA

TTAATACAGAGACTCTTACCAAGGTAAAACCTAAAACAGGTCAGGAAAATGGATGGG AAAAAGAT

GCTACAGAATTTTCAGATAAAAATGAAATAAGAGTTGGAAATAATTTTGCCATGGAA ATCAATCT

AAATGCCAACCTGTGGAGAAATTTCCTGTACTCCAACATAGCGCTGTATTTGCCCGA CAAGCTAAA

GT AC AGTCCTTCC A ACGT A A A A ATTTCTG AT A ACCC A A AC ACCT ACG ACT AC ATG A AC A AGCG AGT

GGTGGCTCCCGGGCTAGTGGACTGCTACATTAACCTTGGAGCACGCTGGTCCCTTGA CTATATGGA

CAACGTCAACCCATTTAACCACCACCGCAATGCTGGCCTGCGCTACCGCTCAATGTT GCTGGGCAA

TGGTCGCTATGTGCCCTTCCACATCCAGGTGCCTCAGAAGTTCTTTGCCATTAAAAA CCTCCTTCTC

CTGCCGGGCTCATACACCTACGAGTGGAACTTCAGGAAGGATGTTAACATGGTTCTG CAGAGCTCC

CT AGG A A ATG ACCT A AGGGTTG ACGG AGCC AGC ATT A AGTTTG AT AGC ATTTGCCTTT ACGCC ACC

TTCTTCCCCATGGCCCACAACACCGCCTCCACGCTTGAGGCCATGCTTAGAAACGAC ACCAACGAC

C AGTCCTTT AACG ACT ATCTCTCCGCCGCC A AC ATGCTCT ACCCT AT ACCCGCC A ACGCT ACC A AC

GTGCCCATATCCATCCCCTCCCGCAACTGGGCGGCTTTCCGCGGCTGGGCCTTCACG CGCCTTAAG

ACT A AGG A A ACCCC ATC ACTGGGCTCGGGCT ACG ACCCTT ATT AC ACCT ACTCTGGCTCT AT ACCC

TACCTAGATGGAACCTTTTACCTCAACCACACCTTTAAGAAGGTGGCCATTACCTTT GACTCTTCTG

TCAGCTGGCCTGGCAATGACCGCCTGCTTACCCCCAACGAGTTTGAAATTAAGCGCT CAGTTGACG

GGGAGGGTTACAACGTTGCCCAGTGTAACATGACCAAAGACTGGTTCCTGGTACAAA TGCTAGCT

A ACT AT A AC ATTGGCT ACC AGGGCTTCT AT ATCCC AG AG AGCT AC A AGG ACCGC ATGT ACTCCTTC

TTTAGAAACTTCCAGCCCATGAGCCGTCAGGTGGTGGATGATACTAAATACAAGGAC TACCAACA

GGTGGGCATCCTACACCAACACAACAACTCTGGATTTGTTGGCTACCTTGCCCCCAC CATGCGCGA

AGG AC AGGCCT ACCCTGCT A ACTTCCCCT ATCCGCTT AT AGGC A AG ACCGC AGTTG AC AGC ATT AC

CCAGAAAAAGTTTCTTTGCGATCGCACCCTTTGGCGCATCCCATTCTCCAGTAACTT TATGTCCATG

GGCGCACTCACAGACCTGGGCCAAAACCTTCTCTACGCCAACTCCGCCCACGCGCTA GACATGACT

TTTGAGGTGGATCCCATGGACGAGCCCACCCTTCTTTATGTTTTGTTTGAAGTCTTT GACGTGGTCC

GTGTGCACCAGCCGCACCGCGGCGTCATCGAAACCGTGTACCTGCGCACGCCCTTCT CGGCCGGCA

ACGCCACAACATAAAGAAGCAAGCAACATCAACAACAGCTGCCGCCATGGGCTCCAG TGAGCAG

GAACTGAAAGCCATTGTCAAAGATCTTGGTTGTGGGCCATATTTTTTGGGCACCTAT GACAAGCGC

TTTCCAGGCTTTGTTTCTCCACACAAGCTCGCCTGCGCCATAGTCAATACGGCCGGT CGCGAGACT

GGGGGCGTACACTGGATGGCCTTTGCCTGGAACCCGCACTCAAAAACATGCTACCTC TTTGAGCCC

TTTGGCTTTTCTGACCAGCGACTCAAGCAGGTTTACCAGTTTGAGTACGAGTCACTC CTGCGCCGT

AGCGCCATTGCTTCTTCCCCCGACCGCTGTATAACGCTGGAAAAGTCCACCCAAAGC GTACAGGGG

CCCAACTCGGCCGCCTGTGGACTATTCTGCTGCATGTTTCTCCACGCCTTTGCCAAC TGGCCCCAAA

CTCCCATGGATCACAACCCCACCATGAACCTTATTACCGGGGTACCCAACTCCATGC TCAACAGTC

CCCAGGTACAGCCCACCCTGCGTCGCAACCAGGAACAGCTCTACAGCTTCCTGGAGC GCCACTCGC

CCTACTTCCGCAGCCACAGTGCGCAGATTAGGAGCGCCACTTCTTTTTGTCACTTGA AAAACATGT

AAAAATAATGTACTAGAGACACTTTCAATAAAGGCAAATGCTTTTATTTGTACACTC TCGGGTGAT

TATTTACCCCCACCCTTGCCGTCTGCGCCGTTTAAAAATCAAAGGGGTTCTGCCGCG CATCGCTAT

GCGCCACTGGCAGGGACACGTTGCGATACTGGTGTTTAGTGCTCCACTTAAACTCAG GCACAACCA

TCCGCGGCAGCTCGGTGAAGTTTTCACTCCACAGGCTGCGCACCATCACCAACGCGT TTAGCAGGT

CGGGCGCCGATATCTTGAAGTCGCAGTTGGGGCCTCCGCCCTGCGCGCGCGAGTTGC GATACACA

GGGTTGCAGCACTGGAACACTATCAGCGCCGGGTGGTGCACGCTGGCCAGCACGCTC TTGTCGGA

GATCAGATCCGCGTCCAGGTCCTCCGCGTTGCTCAGGGCGAACGGAGTCAACTTTGG TAGCTGCCT TCCCAAAAAGGGCGCGTGCCCAGGCTTTGAGTTGCACTCGCACCGTAGTGGCATCAAAAG GTGAC

CGTGCCCGGTCTGGGCGTTAGGATACAGCGCCTGCATAAAAGCCTTGATCTGCTTAA AAGCCACCT

GAGCCTTTGCGCCTTCAGAGAAGAACATGCCGCAAGACTTGCCGGAAAACTGATTGG CCGGACAG

GCCGCGTCGTGCACGCAGCACCTTGCGTCGGTGTTGGAGATCTGCACCACATTTCGG CCCCACCGG

TTCTTCACGATCTTGGCCTTGCTAGACTGCTCCTTCAGCGCGCGCTGCCCGTTTTCG CTCGTCACAT

CC ATTTC A ATC ACGTGCTCCTT ATTT ATC AT A ATGCTTCCGTGT AG AC ACTT A AGCTCGCCTTCG AT

CTCAGCGCAGCGGTGCAGCCACAACGCGCAGCCCGTGGGCTCGTGATGCTTGTAGGT CACCTCTGC

AAACGACTGCAGGTACGCCTGCAGGAATCGCCCCATCATCGTCACAAAGGTCTTGTT GCTGGTGAA

GGTCAGCTGCAACCCGCGGTGCTCCTCGTTCAGCCAGGTCTTGCATACGGCCGCCAG AGCTTCCAC

TTGGTC AGGC AGT AGTTTG A AGTTCGCCTTT AG ATCGTT ATCC ACGTGGT ACTTGTCC ATC AGCGCG

CGCGCAGCCTCCATGCCCTTCTCCCACGCAGACACGATCGGCACACTCAGCGGGTTC ATCACCGTA

ATTTCACTTTCCGCTTCGCTGGGCTCTTCCTCTTCCTCTTGCGTCCGCATACCACGC GCCACTGGGT

CGTCTTCATTCAGCCGCCGCACTGTGCGCTTACCTCCTTTGCCATGCTTGATTAGCA CCGGTGGGTT

GCTGAAACCCACCATTTGTAGCGCCACATCTTCTCTTTCTTCCTCGCTGTCCACGAT TACTTGACAA

TTAATCATCGGCTCGTATAATGATGCAGTACATTTTCACAGGAGGTACAGCTATGAC CATGATTAC

GGATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCA ACTTAATCG

CCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGA TCGCCCTTC

CCAACAGTTGCGCAGCCTGAATGGCGAATAGGTCGCGCCGCACCGCGTCCGCGCTCG GGGGTGGT

TTCGCGCTGCTCCTCTTCCCGACTGGCCATTTCCTTCTCCTATAGGCAGAAAAAGAT CATGGAGTCA

GTCGAGAAGAAGGACAGCCTAACCGCCCCCTCTGAGTTCGCCACCACCGCCTCCACC GATGCCGC

CAACGCGCCTACCACCTTCCCCGTCGAGGCACCCCCGCTTGAGGAGGAGGAAGTGAT TATCGAGC

AGGACCCAGGTTTTGTAAGCGAAGACGACGAGGACCGCTCAGTACCAACAGAGGATA AAAAGCA

AGACCAGGACAACGCAGAGGCAAACGAGGAACAAGTCGGGCGGGGGGACGAAAGGCA TGGCGA

CTACCTAGATGTGGGAGACGACGTGCTGTTGAAGCATCTGCAGCGCCAGTGCGCCAT TATCTGCGA

CGCGTTGCAAGAGCGCAGCGATGTGCCCCTCGCCATAGCGGATGTCAGCCTTGCCTA CGAACGCC

ACCTATTCTCACCGCGCGTACCCCCCAAACGCCAAGAAAACGGCACATGCGAGCCCA ACCCGCGC

CTCAACTTCTACCCCGTATTTGCCGTGCCAGAGGTGCTTGCCACCTATCACATCTTT TTCCAAAACT

GCAAGATACCCCTATCCTGCCGTGCCAACCGCAGCCGAGCGGACAAGCAGCTGGCCT TGCGGCAG

GGCGCTGTCATACCTGATATCGCCTCGCTCAACGAAGTGCCAAAAATCTTTGAGGGT CTTGGACGC

GACGAGAAGCGCGCGGCAAACGCTCTGCAACAGGAAAACAGCGAAAATGAAAGTCAC TCTGGAG

TGTTGGTGGAACTCGAGGGTGACAACGCGCGCCTAGCCGTACTAAAACGCAGCATCG AGGTCACC

CACTTTGCCTACCCGGCACTTAACCTACCCCCCAAGGTCATGAGCACAGTCATGAGT GAGCTGATC

GTGCGCCGTGCGCAGCCCCTGGAGAGGGATGCAAATTTGCAAGAACAAACAGAGGAG GGCCTACC

CGCAGTTGGCGACGAGCAGCTAGCGCGCTGGCTTCAAACGCGCGAGCCTGCCGACTT GGAGGAGC

GACGCAAACTAATGATGGCCGCAGTGCTCGTTACCGTGGAGCTTGAGTGCATGCAGC GGTTCTTTG

CTGACCCGGAGATGCAGCGCAAGCTAGAGGAAACATTGCACTACACCTTTCGACAGG GCTACGTA

CGCCAGGCCTGCAAGATCTCCAACGTGGAGCTCTGCAACCTGGTCTCCTACCTTGGA ATTTTGCAC

GAAAACCGCCTTGGGCAAAACGTGCTTCATTCCACGCTCAAGGGCGAGGCGCGCCGC GACTACGT

CCGCGACTGCGTTTACTTATTTCTATGCTACACCTGGCAGACGGCCATGGGCGTTTG GCAGCAGTG

CTTGGAGGAGTGCAACCTCAAGGAGCTGCAGAAACTGCTAAAGCAAAACTTGAAGGA CCTATGGA

CGGCCTTCAACGAGCGCTCCGTGGCCGCGCACCTGGCGGACATCATTTTCCCCGAAC GCCTGCTTA

AAACCCTGCAACAGGGTCTGCCAGACTTCACCAGTCAAAGCATGTTGCAGAACTTTA GGAACTTTA

TCCTAGAGCGCTCAGGAATCTTGCCCGCCACCTGCTGTGCACTTCCTAGCGACTTTG TGCCCATTAA

GTACCGCGAATGCCCTCCGCCGCTTTGGGGCCACTGCTACCTTCTGCAGCTAGCCAA CTACCTTGC

CTACCACTCTGACATAATGGAAGACGTGAGCGGTGACGGTCTACTGGAGTGTCACTG TCGCTGCAA

CCTATGCACCCCGCACCGCTCCCTGGTTTGCAATTCGCAGCTGCTTAACGAAAGTCA AATTATCGG

TACCTTTGAGCTGCAGGGTCCCTCGCCTGACGAAAAGTCCGCGGCTCCGGGGTTGAA ACTCACTCC

GGGGCTGTGGACGTCGGCTTACCTTCGCAAATTTGTACCTGAGGACTACCACGCCCA CGAGATTAG

GTTCTACGAAGACCAATCCCGCCCGCCTAATGCGGAGCTTACCGCCTGCGTCATTAC CCAGGGCCA

CATTCTTGGCCAATTGCAAGCCATCAACAAAGCCCGCCAAGAGTTTCTGCTACGAAA GGGACGGG

GGGTTTACTTGGACCCCCAGTCCGGCGAGGAGCTCAACCCAATCCCCCCGCCGCCGC AGCCCTATC

AGCAGCAGCCGCGGGCCCTTGCTTCCCAGGATGGCACCCAAAAAGAAGCTGCAGCTG CCGCCGCC

ACCCACGGACGAGGAGGAATACTGGGACAGTCAGGCAGAGGAGGTTTTGGACGAGGA GGAGGAG

GACATGATGGAAGACTGGGAGAGCCTAGACGAGGAAGCTTCCGAGGTCGAAGAGGTG TCAGACG

AAACACCGTCACCCTCGGTCGCATTCCCCTCGCCGGCGCCCCAGAAATCGGCAACCG GTTCCAGCA

TGGCTACAACCTCCGCTCCTCAGGCGCCGCCGGCACTGCCCGTTCGCCGACCCAACC GTAGATGGG

ACACCACTGGAACCAGGGCCGGTAAGTCCAAGCAGCCGCCGCCGTTAGCCCAAGAGC AACAACAG

CGCCAAGGCTACCGCTCATGGCGCGGGCACAAGAACGCCATAGTTGCTTGCTTGCAA GACTGTGG

GGGCAACATCTCCTTCGCCCGCCGCTTTCTTCTCTACCATCACGGCGTGGCCTTCCC CCGTAACATC CTGCATTACTACCGTCATCTCTACAGCCCATACTGCACCGGCGGCAGCGGCAGCAACAGC AGCGG

CCACACAGAAGCAAAGGCGACCGGATAGCAAGACTCTGACAAAGCCCAAGAAATCCA CAGCGGC

GGCAGCAGCAGGAGGAGGAGCGCTGCGTCTGGCGCCCAACGAACCCGTATCGACCCG CGAGCTTA

GAAACAGGATTTTTCCCACTCTGTATGCTATATTTCAACAGAGCAGGGGCCAAGAAC AAGAGCTG

AAAATAAAAAACAGGTCTCTGCGATCCCTCACCCGCAGCTGCCTGTATCACAAAAGC GAAGATCA

GCTTCGGCGCACGCTGGAAGACGCGGAGGCTCTCTTCAGTAAATACTGCGCGCTGAC TCTTAAGGA

CT AGTTTCGCGCCCTTTCTC A A ATTT A AGCGCG A A A ACT ACGTC ATCTCC AGCGGCC AC ACCCGGC

GCCAGCACCTGTTGTCAGCGCCATTATGAGCAAGGAAATTCCCACGCCCTACATGTG GAGTTACCA

GCCACAAATGGGACTTGCGGCTGGAGCTGCCCAAGACTACTCAACCCGAATAAACTA CATGAGCG

CGGGACCCCACATGATATCCCGGGTCAACGGAATACGCGCCCACCGAAACCGAATTC TCCTGGAA

C AGGCGGCT ATT ACC ACC AC ACCTCGT A AT A ACCTT A ATCCCCGT AGTTGGCCCGCTGCCCTGGTG

TACCAGGAAAGTCCCGCTCCCACCACTGTGGTACTTCCCAGAGACGCCCAGGCCGAA GTTCAGAT

GACTAACTCAGGGGCGCAGCTTGCGGGCGGCTTTCGTCACAGGGTGCGGTCGCCCGG GCAGGGTA

TAACTCACCTGACAATCAGAGGGCGAGGTATTCAGCTCAACGACGAGTCGGTGAGCT CCTCGCTTG

GTCTCCGTCCGGACGGGACATTTCAGATCGGCGGCGCCGGCCGCTCTTCATTCACGC CTCGTCAGG

CAATCCTAACTCTGCAGACCTCGTCCTCTGAGCCGCGCTCTGGAGGCATTGGAACTC TGCAATTTA

TTGAGGAGTTTGTGCCATCGGTCTACTTTAACCCCTTCTCGGGACCTCCCGGCCACT ATCCGGATCA

ATTTATTCCTAACTTTGACGCGGTAAAGGACTCGGCGGACGGCTACGACTGAATGTT AAGTGGAGA

GGCAGAGCAACTGCGCCTGAAACACCTGGTCCACTGTCGCCGCCACAAGTGCTTTGC CCGCGACTC

CGGTGAGTTTTGCTACTTTGAATTGCCCGAGGATCATATCGAGGGCCCGGCGCACGG CGTCCGGCT

TACCGCCCAGGGAGAGCTTGCCCGTAGCCTGATTCGGGAGTTTACCCAGCGCCCCCT GCTAGTTGA

GCGGGACAGGGGACCCTGTGTTCTCACTGTGATTTGCAACTGTCCTAACCCTGGATT ACATCAAGA

TCTTTGTTGCCATCTCTGTGCTGAGTATAATAAATACAGAAATTAAAATATACTGGG GCTCCTATC

GCCATCCTGTAAACGCCACCGTCTTCACCCGCCCAAGCAAACCAAGGCGAACCTTAC CTGGTACTT

TTAACATCTCTCCCTCTGTGATTTACAACAGTTTCAACCCAGACGGAGTGAGTCTAC GAGAGAACC

TCTCCGAGCTCAGCTACTCCATCAGAAAAAACACCACCCTCCTTACCTGCCGGGAAC GTACGAGTG

CGTCACCGGCCGCTGCACCACACCTACCGCCTGACCGTAAACCAGACTTTTTCCGGA CAGACCTCA

ATAACTCTGTTTACCAGAACAGGAGGTGAGCTTAGAAAACCCTTAGGGTATTAGGCC AAAGGCGC

AGCT ACTGTGGGGTTT ATG A AC A ATTC A AGC A ACTCT ACGGGCT ATTCT A ATTC AGGTTTCTCT AG

AAATGGACGGAATTATTACAGAGCAGCGCCTGCTAGAAAGACGCAGGGCAGCGGCCG AGCAACA

GCGCATGAATCAAGAGCTCCAAGACATGGTTAACTTGCACCAGTGCAAAAGGGGTAT CTTTTGTCT

GGTAAAGCAGGCCAAAGTCACCTACGACAGTAATACCACCGGACACCGCCTTAGCTA CAAGTTGC

CAACCAAGCGTCAGAAATTGGTGGTCATGGTGGGAGAAAAGCCCATTACCATAACTC AGCACTCG

GTAGAAACCGAAGGCTGCATTCACTCACCTTGTCAAGGACCTGAGGATCTCTGCACC CTTATTAAG

ACCCTGTGCGGTCTC A A AG ATCTT ATTCCCTTT A ACT A AT A A A A A A A A AT A AT A A AGC ATC ACTT A

CTTAAAATCAGTTAGCAAATTTCTGTCCAGTTTATTCAGCAGCACCTCCTTGCCCTC CTCCCAGCTC

TGGTATTGCAGCTTCCTCCTGGCTGCAAACTTTCTCCACAATCTAAATGGAATGTCA GTTTCCTCCT

GTTCCTGTCCATCCGCACCCACTATCTTCATGTTGTTGCAGATGAAGCGCGCAAGAC CGTCTGAAG

ATACCTTCAACCCCGTGTATCCATATGACACGGAAACCGGTCCTCCAACTGTGCCTT TTCTTACTCC

TCCCTTTGTATCCCCCAATGGGTTTCAAGAGAGTCCCCCTGGGGTACTCTCTTTGCG CCTATCCGAA

CCTCTAGTTACCTCCAATGGCATGCTTGCGCTCAAAATGGGCAACGGCCTCTCTCTG GACGAGGCC

GGCAACCTTACCTCCCAAAATGTAACCACTGTGAGCCCACCTCTCAAAAAAACCAAG TCAAACAT

AAACCTGGAAATATCTGCACCCCTCACAGTTACCTCAGAAGCCCTAACTGTGGCTGC CGCCGCACC

TCTAATGGTCGCGGGCAACACACTCACCATGCAATCACAGGCCCCGCTAACCGTGCA CGACTCCA

AACTTAGCATTGCCACCCAAGGACCCCTCACAGTGTCAGAAGGAAAGCTAGCCCTGC AAACATCA

GGCCCCCTC ACC ACC ACCG AT AGC AGT ACCCTT ACT ATC ACTGCCTC ACCCCCTCT A ACT ACTGCC

ACTGGTAGCTTGGGCATTGACTTGAAAGAGCCCATTTATACACAAAATGGAAAACTA GGACTAAA

GTACGGGGCTCCTTTGCATGTAACAGACGACCTAAACACTTTGACCGTAGCAACTGG TCCAGGTGT

GACTATTAATAATACTTCCTTGCAAACTAAAGTTACTGGAGCCTTGGGTTTTGATTC ACAAGGCAA

TATGCAACTTAATGTAGCAGGAGGACTAAGGATTGATTCTCAAAACAGACGCCTTAT ACTTGATGT

T AGTT ATCCGTTTG ATGCTC A A A ACC A ACT A A ATCT A AG ACT AGG AC AGGGCCCTCTTTTT AT AAA

CTC AGCCC AC A ACTTGG AT ATT A ACT AC A AC A A AGGCCTTT ACTTGTTT AC AGCTTC A A AC A ATTC

CAAAAAGCTTGAGGTTAACCTAAGCACTGCCAAGGGGTTGATGTTTGACGCTACAGC CATAGCCA

TTAATGCAGGAGATGGGCTTGAATTTGGTTCACCTAATGCACCAAACACAAATCCCC TCAAAACAA

AAATTGGCCATGGCCTAGAATTTGATTCAAACAAGGCTATGGTTCCTAAACTAGGAA CTGGCCTTA

GTTTTGACAGCACAGGTGCCATTACAGTAGGAAACAAAAATAATGATAAGCTAACTT TGTGGACC

ACACCAGCTCCATCTCCTAACTGTAGACTAAATGCAGAGAAAGATGCTAAACTCACT TTGGTCTTA

ACAAAATGTGGCAGTCAAATACTTGCTACAGTTTCAGTTTTGGCTGTTAAAGGCAGT TTGGCTCCA

ATATCTGGAACAGTTCAAAGTGCTCATCTTATTATAAGATTTGACGAAAATGGAGTG CTACTAAAC AATTCCTTCCTGGACCCAGAATATTGGAACTTTAGAAATGGAGATCTTACTGAAGGCACA GCCTAT

ACAAACGCTGTTGGATTTATGCCTAACCTATCAGCTTATCCAAAATCTCACGGTAAA ACTGCCAAA

AGT A AC ATTGTC AGTC A AGTTT ACTT A A ACGG AG AC A A A ACT A A ACCTGT AAC ACT A ACC ATT AC A

CTAAACGGTACACAGGAAACAGGAGACACAACTCCAAGTGCATACTCTATGTCATTT TCATGGGA

CTGGTCTGGCCACAACTACATTAATGAAATATTTGCCACATCCTCTTACACTTTTTC ATACATTGCC

CAAGAATAAAGAATCGTTTGTGTTATGTTTCAACGTGTTTATTTTTCAATTGCAGAA AATTTCGAAT

C ATTTTTC ATTC AGT AGT AT AGCCCC ACC ACC AC AT AGCTT AT AC AG ATC ACCGT ACCTT A ATC A A

ACTC AC AG A ACCCT AGT ATTC A ACCTGCC ACCTCCCTCCC A AC AC AC AG AGT AC AC AGTCCTTTCT

CCCCGGCTGGCCTT AA A A AGC ATC AT ATC ATGGGT A AC AG AC AT ATTCTT AGGTGTT AT ATTCC AC

ACGGTTTCCTGTCG AGCC A A ACGCTC ATC AGTG AT ATT AAT A A ACTCCCCGGGC AGCTC ACTT A AG

TTCATGTCGCTGTCCAGCTGCTGAGCCACAGGCTGCTGTCCAACTTGCGGTTGCTTA ACGGGCGGC

GAAGGAGAAGTCCACGCCTACATGGGGGTAGAGTCATAATCGTGCATCAGGATAGGG CGGTGGTG

CTGCAGCAGCGCGCGAATAAACTGCTGCCGCCGCCGCTCCGTCCTGCAGGAATACAA CATGGCAG

TGGTCTCCTCAGCGATGATTCGCACCGCCCGCAGCATAAGGCGCCTTGTCCTCCGGG CACAGCAGC

GCACCCTGATCTCACTTAAATCAGCACAGTAACTGCAGCACAGCACCACAATATTGT TCAAAATCC

CACAGTGCAAGGCGCTGTATCCAAAGCTCATGGCGGGGACCACAGAACCCACGTGGC CATCATAC

C AC A AGCGC AGGT AG ATT AAGTGGCG ACCCCTC AT A A AC ACGCTGG AC AT A A AC ATT ACCTCTTTT

GGCATGTTGTAATTCACCACCTCCCGGTACCATATAAACCTCTGATTAAACATGGCG CCATCCACC

ACCATCCTAAACCAGCTGGCCAAAACCTGCCCGCCGGCTATACACTGCAGGGAACCG GGACTGGA

ACAATGACAGTGGAGAGCCCAGGACTCGTAACCATGGATCATCATGCTCGTCATGAT ATCAATGTT

GGCACAACACAGGCACACGTGCATACACTTCCTCAGGATTACAAGCTCCTCCCGCGT TAGAACCAT

ATCCCAGGGAACAACCCATTCCTGAATCAGCGTAAATCCCACACTGCAGGGAAGACC TCGCACGT

AACTCACGTTGTGCATTGTCAAAGTGTTACATTCGGGCAGCAGCGGATGATCCTCCA GTATGGTAG

CGCGGGTTTCTGTCTCAAAAGGAGGTAGACGATCCCTACTGTACGGAGTGCGCCGAG ACAACCGA

GATCGTGTTGGTCGTAGTGTCATGCCAAATGGAACGCCGGACGTAGTCATATTTCCT GAAGCAAAA

CCAGGTGCGGGCGTGACAAACAGATCTGCGTCTCCGGTCTCGCCGCTTAGATCGCTC TGTGTAGTA

GTTGT AGT AT ATCC ACTCTCTC A A AGC ATCC AGGCGCCCCCTGGCTTCGGGTTCT ATGT A A ACTCCT

TCATGCGCCGCTGCCCTGATAACATCCACCACCGCAGAATAAGCCACACCCAGCCAA CCTACACAT

TCGTTCTGCGAGTCACACACGGGAGGAGCGGGAAGAGCTGGAAGAACCATGTTTTTT TTTTTATTC

CAAAAGATTATCCAAAACCTCAAAATGAAGATCTATTAAGTGAACGCGCTCCCCTCC GGTGGCGT

GGTCAAACTCTACAGCCAAAGAACAGATAATGGCATTTGTAAGATGTTGCACAATGG CTTCCAAA

AGGCAAACGGCCCTCACGTCCAAGTGGACGTAAAGGCTAAACCCTTCAGGGTGAATC TCCTCTAT

A A AC ATTCC AGC ACCTTC A ACC ATGCCC A A AT A ATTCTC ATCTCGCC ACCTTCTC A AT AT ATCTCT A

AGCAAATCCCGAATATTAAGTCCGGCCATTGTAAAAATCTGCTCCAGAGCGCCCTCC ACCTTCAGC

CTCAAGCAGCGAATCATGATTGCAAAAATTCAGGTTCCTCACAGACCTGTATAAGAT TCAAAAGC

GGAACATTAACAAAAATACCGCGATCCCGTAGGTCCCTTCGCAGGGCCAGCTGAACA TAATCGTG

CAGGTCTGCACGGACCAGCGCGGCCACTTCCCCGCCAGGAACCATGACAAAAGAACC CACACTGA

TTATGACACGCATACTCGGAGCTATGCTAACCAGCGTAGCCCCGATGTAAGCTTGTT GCATGGGCG

GCGATATAAAATGCAAGGTGCTGCTCAAAAAATCAGGCAAAGCCTCGCGCAAAAAAG AAAGCAC

ATCGTAGTCATGCTCATGCAGATAAAGGCAGGTAAGCTCCGGAACCACCACAGAAAA AGACACCA

TTTTTCTCTCAAACATGTCTGCGGGTTTCTGCATAAACACAAAATAAAATAACAAAA AAACATTTA

AACATTAGAAGCCTGTCTTACAACAGGAAAAACAACCCTTATAAGCATAAGACGGAC TACGGCCA

TGCCGGCGTGACCGTAAAAAAACTGGTCACCGTGATTAAAAAGCACCACCGACAGCT CCTCGGTC

ATGTCCGGAGTCATAATGTAAGACTCGGTAAACACATCAGGTTGATTCACATCGGTC AGTGCTAAA

AAGCGACCGAAATAGCCCGGGGGAATACATACCCGCAGGCGTAGAGACAACATTACA GCCCCCAT

AGGAGGTATAACAAAATTAATAGGAGAGAAAAACACATAAACACCTGAAAAACCCTC CTGCCTAG

GCAAAATAGCACCCTCCCGCTCCAGAACAACATACAGCGCTTCCACAGCGGCAGCCA TAACAGTC

AGCCTT ACC AGT A A A A A AG A A A ACCT ATT A A A A A A AC ACC ACTCG AC ACGGC ACC AGCTC A ATC A

GTCACAGTGTAAAAAAGGGCCAAGTGCAGAGCGAGTATATATAGGACTAAAAAATGA CGTAACG

GTTAAAGTCCACAAAAAACACCCAGAAAACCGCACGCGAACCTACGCCCAGAAACGA AAGCCAA

AAAACCCACAACTTCCTCAAATCGTCACTTCCGTTTTCCCACGTTACGTCACTTCCC ATTTTAAGAA

A ACT AC A ATTCCC A AC AC AT AC A AGTT ACTCCGCCCT A A A ACCT ACGTC ACCCGCCCCGTTCCC AC

GCCCCGCGCCACGTCACAAACTCCACCCCCTCATTATCATATTGGCTTCAATCCAAA ATAAGGTAT

ATTATTGATGATGTTAATTAATTTAAATCCGCATGCGATATCGAGCTCTCCCGGGAA TTCGGATCT

GCGACGCGAGGCTGGATGGCCTTCCCCATTATGATTCTTCTCGCGTTTAAGGGCACC AATAACTGC

CTTAAAAAAATTACGCCCCGCCCTGCCACTCATCGCAGTACTGTTGTAATTCATTAA GCATTCTGCC

GACATGGAAGCCATCACAAACGGCATGATGAACCTGAATCGCCAGCGGCATCAGCAC CTTGTCGC

CTTGCGTATAATATTTGCCCATGGTGAAAACGGGGGCGAAGAAGTTGTCCATATTGG CCACGTTTA

AATCAAAACTGGTGAAACTCACCCAGGGATTGGCTGAGACGAAAAACATATTCTCAA TAAACCCT TTAGGGAAATAGGCCAGGTTTTCACCGTAACACGCCACATCTTGCGAATATATGTGTAGA AACTGC

CGGAAATCGTCGTGGTATTCACTCCAGAGCGATGAAAACGTTTCAGTTTGCTCATGG AAAACGGTG

T AAC A AGGGTG A AC ACT ATCCC AT ATC ACC AGCTC ACCGTCTTTC ATTGCC AT ACGG A ATTCCGG A

TGAGCATTCATCAGGCGGGCAAGAATGTGAATAAAGGCCGGATAAAACTTGTGCTTA TTTTTCTTT

ACGGTCTTT A A A A AGGCCGT A AT ATCC AGCTG A ACGGTCTGGTT AT AGGT AC ATTG AGC A ACTG AC

TGAAATGCCTCAAAATGTTCTTTACGATGCCATTGGGATATATCAACGGTGGTATAT CCAGTGATT

TTTTTCTCC ATTTT AGCTTCCTT AGCTCCTG A A A ATCTCG AT A ACTC A A A A A AT ACGCCCGGT AGTG

ATCTTATTTCATTATGGTGAAAGTTGGAACCTCTTACGTGCCGATCAACGTCTCATT TTCGCCAAAA

GTTGGCCCAGGGCTTCCCGGTATCAACAGGGACACCAGGATTTATTTATTCTGCGAA GTGATCTTC

CGTCACAGGTATTTATTCGCGATAAGCTCATGGAGCGGCGTAACCGTCGCACAGGAA GGACAGAG

AAAGCGCGGATCTGGGAAGTGACGGACAGAACGGTCAGGACCTGGATTGGGGAGGCG GTTGCCG

CCGCTGCTGCTGACGGTGTGACGTTCTCTGTTCCGGTCACACCACATACGTTCCGCC ATTCCTATGC

GATGCACATGCTGTATGCCGGTATACCGCTGAAAGTTCTGCAAAGCCTGATGGGACA TAAGTCCAT

CAGTTCAACGGAAGTCTACACGAAGGTTTTTGCGCTGGATGTGGCTGCCCGGCACCG GGTGCAGTT

TGCGATGCCGGAGTCTGATGCGGTTGCGATGCTGAAACAATTATCCTGAGAATAAAT GCCTTGGCC

TTTATATGGAAATGTGGAACTGAGTGGATATGCTGTTTTTGTCTGTTAAACAGAGAA GCTGGCTGT

T ATCC ACTG AG A AGCG A ACG A A AC AGTCGGG A A A ATCTCCC ATT ATCGT AG AG ATCCGC ATT ATT

AATCTCAGGAGCCTGTGTAGCGTTTATAGGAAGTAGTGTTCTGTCATGATGCCTGCA AGCGGTAAC

GAAAACGATTTGAATATGCCTTCAGGAACAATAGAAATCTTCGTGCGGTGTTACGTT GAAGTGGA

GCGGATTATGTCAGCAATGGACAGAACAACCTAATGAACACAGAACCATGATGTGGT CTGTCCTTT

TACAGCCAGTAGTGCTCGCCGCAGTCGAGCGACAGGGCGAAGCCCTCGAGTGAGCGA GGAAGCAC

CAGGGAACAGCACTTATATATTCTGCTTACACACGATGCCTGAAAAAACTTCCCTTG GGGTTATCC

ACTT ATCC ACGGGG AT ATTTTT AT A ATT ATTTTTTTTAT AGTTTTT AG ATCTTCTTTTTT AG AGCGCC

TTGTAGGCCTTTATCCATGCTGGTTCTAGAGAAGGTGTTGTGACAAATTGCCCTTTC AGTGTGACA

AATCACCCTCAAATGACAGTCCTGTCTGTGACAAATTGCCCTTAACCCTGTGACAAA TTGCCCTCA

GAAGAAGCTGTTTTTTCACAAAGTTATCCCTGCTTATTGACTCTTTTTTATTTAGTG TGACAATCTA

AAAACTTGTCACACTTCACATGGATCTGTCATGGCGGAAACAGCGGTTATCAATCAC AAGAAACG

TAAAAATAGCCCGCGAATCGTCCAGTCAAACGACCTCACTGAGGCGGCATATAGTCT CTCCCGGG

ATCAAAAACGTATGCTGTATCTGTTCGTTGACCAGATCAGAAAATCTGATGGCACCC TACAGGAAC

ATGACGGTATCTGCGAGATCCATGTTGCTAAATATGCTGAAATATTCGGATTGACCT CTGCGGAAG

CCAGTAAGGATATACGGCAGGCATTGAAGAGTTTCGCGGGGAAGGAAGTGGTTTTTT ATCGCCCT

GAAGAGGATGCCGGCGATGAAAAAGGCTATGAATCTTTTCCTTGGTTTATCAAACGT GCGCACAGT

CC ATCC AG AGGGCTTT AC AGTGT AC AT ATC A ACCC AT ATCTC ATTCCCTTCTTT ATCGGGTT AC AG A

ACCGGTTTACGCAGTTTCGGCTTAGTGAAACAAAAGAAATCACCAATCCGTATGCCA TGCGTTTAT

ACG AATCCCTGTGTCAGT ATCGT AAGCCGGATGGCTCAGGCATCGTCTCTCTGAAAATCGACTGGA

TCATAGAGCGTTACCAGCTGCCTCAAAGTTACCAGCGTATGCCTGACTTCCGCCGCC GCTTCCTGC

AGGTCTGTGTTAATGAGATCAACAGCAGAACTCCAATGCGCCTCTCATACATTGAGA AAAAGAAA

GGCCGCC AG ACG ACTC AT ATCGT ATTTTCCTTCCGCG AT ATC ACTTCC ATG ACG AC AGG AT AGTCT

GAGGGTTATCTGTCACAGATTTGAGGGTGGTTCGTCACATTTGTTCTGACCTACTGA GGGTAATTT

GTCACAGTTTTGCTGTTTCCTTCAGCCTGCATGGATTTTCTCATACTTTTTGAACTG TAATTTTTAAG

GAAGCCAAATTTGAGGGCAGTTTGTCACAGTTGATTTCCTTCTCTTTCCCTTCGTCA TGTGACCTGA

TATCGGGGGTTAGTTCGTCATCATTGATGAGGGTTGATTATCACAGTTTATTACTCT GAATTGGCTA

TCCGCGTGTGTACCTCTACCTGGAGTTTTTCCCACGGTGGATATTTCTTCTTGCGCT GAGCGTAAGA

GCTATCTGACAGAACAGTTCTTCTTTGCTTCCTCGCCAGTTCGCTCGCTATGCTCGG TTACACGGCT

GCGGCGAGCGCTAGTGATAATAAGTGACTGAGGTATGTGCTCTTCTTATCTCCTTTT GTAGTGTTGC

TCTT ATTTT AAACAACTTTGCGGTTTTTT GAT GACTTTGCGATTTT GTT GTT GCTTTGCAGT A A ATT G

CAAGATTTAATAAAAAAACGCAAAGCAATGATTAAAGGATGTTCAGAATGAAACTCA TGGAAACA

CTTAACCAGTGCATAAACGCTGGTCATGAAATGACGAAGGCTATCGCCATTGCACAG TTTAATGAT

GACAGCCCGGAAGCGAGGAAAATAACCCGGCGCTGGAGAATAGGTGAAGCAGCGGAT TTAGTTG

GGGTTTCTTCTCAGGCTATCAGAGATGCCGAGAAAGCAGGGCGACTACCGCACCCGG ATATGGAA

ATTCGAGGACGGGTTGAGCAACGTGTTGGTTATACAATTGAACAAATTAATCATATG CGTGATGTG

TTTGGTACGCGATTGCGACGTGCTGAAGACGTATTTCCACCGGTGATCGGGGTTGCT GCCCATAAA

GGTGGCGTTTACAAAACCTCAGTTTCTGTTCATCTTGCTCAGGATCTGGCTCTGAAG GGGCTACGT

GTTTTGCTCGTGGAAGGTAACGACCCCCAGGGAACAGCCTCAATGTATCACGGATGG GTACCAGA

TCTTCATATTCATGCAGAAGACACTCTCCTGCCTTTCTATCTTGGGGAAAAGGACGA TGTCACTTAT

GCAATAAAGCCCACTTGCTGGCCGGGGCTTGACATTATTCCTTCCTGTCTGGCTCTG CACCGTATTG

AAACTGAGTTAATGGGCAAATTTGATGAAGGTAAACTGCCCACCGATCCACACCTGA TGCTCCGA

CTGGCCATTGAAACTGTTGCTCATGACTATGATGTCATAGTTATTGACAGCGCGCCT AACCTGGGT

ATCGGCACGATTAATGTCGTATGTGCTGCTGATGTGCTGATTGTTCCCACGCCTGCT GAGTTGTTTG ACTACACCTCCGCACTGCAGTTTTTCGATATGCTTCGTGATCTGCTCAAGAACGTTGATC TTAAAGG

GTTCGAGCCTGATGT ACGT ATTTTGCTTACCAAAT ACAGC AAT AGT AATGGCTCTCAGTCCCCGTG

GATGGAGGAGCAAATTCGGGATGCCTGGGGAAGCATGGTTCTAAAAAATGTTGTACG TGAAACGG

ATGAAGTTGGTAAAGGTCAGATCCGGATGAGAACTGTTTTTGAACAGGCCATTGATC AACGCTCTT

CAACTGGTGCCTGGAGAAATGCTCTTTCTATTTGGGAACCTGTCTGCAATGAAATTT TCGATCGTCT

GATTAAACCACGCTGGGAGATTAGATAATGAAGCGTGCGCCTGTTATTCCAAAACAT ACGCTCAAT

ACTCAACCGGTTGAAGATACTTCGTTATCGACACCAGCTGCCCCGATGGTGGATTCG TTAATTGCG

CGCGTAGGAGTAATGGCTCGCGGTAATGCCATTACTTTGCCTGTATGTGGTCGGGAT GTGAAGTTT

ACTCTTGAAGTGCTCCGGGGTGATAGTGTTGAGAAGACCTCTCGGGTATGGTCAGGT AATGAACGT

GACCAGGAGCTGCTTACTGAGGACGCACTGGATGATCTCATCCCTTCTTTTCTACTG ACTGGTCAA

CAGACACCGGCGTTCGGTCGAAGAGTATCTGGTGTCATAGAAATTGCCGATGGGAGT CGCCGTCG

TAAAGCTGCTGCACTTACCGAAAGTGATTATCGTGTTCTGGTTGGCGAGCTGGATGA TGAGCAGAT

GGCTGCATTATCCAGATTGGGTAACGATTATCGCCCAACAAGTGCTTATGAACGTGG TCAGCGTTA

TGCAAGCCGATTGCAGAATGAATTTGCTGGAAATATTTCTGCGCTGGCTGATGCGGA AAATATTTC

ACGT AAGATT ATT ACCCGCTGTATCAACACCGCCAAATTGCCTAAATCAGTTGTTGCTCTTTTTTCT

CACCCCGGTGAACTATCTGCCCGGTCAGGTGATGCACTTCAAAAAGCCTTTACAGAT AAAGAGGA

ATTACTTAAGCAGCAGGCATCTAACCTTCATGAGCAGAAAAAAGCTGGGGTGATATT TGAAGCTG

A AG A AGTT ATC ACTCTTTT A ACTTCTGTGCTT AA A ACGTC ATCTGC ATC A AG A ACT AGTTT AAGCTC

ACGACATCAGTTTGCTCCTGGAGCGACAGTATTGTATAAGGGCGATAAAATGGTGCT TAACCTGGA

CAGGTCTCGTGTTCCAACTGAGTGTATAGAGAAAATTGAGGCCATTCTTAAGGAACT TGAAAAGCC

AGCACCCTGATGCGACCACGTTTTAGTCTACGTTTATCTGTCTTTACTTAATGTCCT TTGTTACAGG

CCAGAAAGCATAACTGGCCTGAATATTCTCTCTGGGCCCACTGTTCCACTTGTATCG TCGGTCTGAT

AATCAGACTGGGACCACGGTCCCACTCGTATCGTCGGTCTGATTATTAGTCTGGGAC CACGGTCCC

ACTCGT ATCGTCGGTCTG ATT ATT AGTCTGGG ACC ACGGTCCC ACTCGT ATCGTCGGTCTG AT A ATC

AGACTGGGACCACGGTCCCACTCGTATCGTCGGTCTGATTATTAGTCTGGGACCATG GTCCCACTC

GT ATCGTCGGTCTG ATT ATT AGTCTGGG ACC ACGGTCCC ACTCGT ATCGTCGGTCTG ATT ATT AGTC

TGGAACCACGGTCCCACTCGTATCGTCGGTCTGATTATTAGTCTGGGACCACGGTCC CACTCGTAT

CGTCGGTCTGATTATTAGTCTGGGACCACGATCCCACTCGTGTTGTCGGTCTGATTA TCGGTCTGGG

ACCACGGTCCCACTTGTATTGTCGATCAGACTATCAGCGTGAGACTACGATTCCATC AATGCCTGT

CAAGGGCAAGTATTGACATGTCGTCGTAACCTGTAGAACGGAGTAACCTCGGTGTGC GGTTGTATG

CCTGCTGTGGATTGCTGCTGTGTCCTGCTTATCCACAACATTTTGCGCACGGTTATG TGGACAAAAT

ACCTGGTTACCCAGGCCGTGCCGGCACGTTAACCGGGCACATTTCCCCGAAAAGTGC CACCTGACG

TCT A AG A A ACC ATT ATT ATC ATG AC ATT A ACCT AT A A A A AT AGGCGT ATC ACG AGGCCCTTTCGTC

TTC A AG A ATTGG ATCCG A ATTCCCGGG AG AGCTCG AT ATCGC ATGCGG ATTT AA ATT A ATT A A

* tadA-Only del araA-leu7697 insertion (SEQ ID NO: 88)

ACGGCGTCCGCAACCGGACGATAATTTTTCTGCTCTTCAACGAACTGCGCAAAATCGTGG AAACGG

TTCGGGTCCAGCAGACGCAGACGGGCGAAGTGGCTTTCCATCCCCAGCTGTTCCGGG GTCGCGGTC

AGCAGCAGAACGCCCGGCACGTGCTCTGCCAGTTGTTCAATGGCCTGATTCGAGAAA GAGTGTTG

ACTTGTGAGCGGATAACAATGATACTTAGATTCAATTGTGAGCGGATAACAATTTCA CACAGGCTA

GCG A ATTCG AGCTCCCTCT AG A A AT A ATTTTGTTT A ACTTT AAG A AGG AG AT AT ACC ATGGGC AGC

AGCT ACCC AT ACG ACGT ACC AG ATT ACGCTTCCG A AGTCG AGTTTTCCC ATG AGT ACTGG ATG AG A

CACGCATTGACTCTCGCAAAGAGGGCTCGAGATGAACGCGAGGTGCCCGTGGGGGCA GTACTCGT

GCTCAACAATCGCGTAATCGGCGAAGGTTGGAATAGGGCAATCGGACTCCACGACCC CACTGCAC

ATGCGGAAATCATGGCCCTTCGACAGGGAGGGCTTGTGATGCAGAATTATCGACTTA TCGATGCG

ACGCTGTACGTCACGTTTGAACCTTGCGTAATGTGCGCGGGAGCTATGATTCACTCC CGCATTGGA

CGAGTTGTATTCGGTGTTCGCAACGCCAAGACGGGTGCCGCAGGTTCACTGATGGAC GTGCTGCAT

TACCCAGGCATGAACCACCGGGTAGAAATCACAGAAGGCATATTGGCGGACGAATGT GCGGCGCT

GTTGTGTTACTTTTTTCGCATGCCCAGGCAGGTCTTTAACGCCCAGAAAAAAGCACA ATCCTCTAC

TGACTTGAACGCCAGGCGCGGCAACGGGGTTATCAACTGCTGATTGCCTGCTCAGAA GATCAGCC

AGACAACGAAATGCGGTGCATTGAGCACCTTTTACAGCGTCAGGTTGATGCCATTAT TGTTTCGAC

GTCGTTGCCTCCTGAGCATCCTTTTTATCAACGCTGGGCTAACGACCCGTTCCCGAT TGTCGCGCTG

G

* tadA-XTEN-T7 del araA-leu7697 insertion (SEQ ID NO: 89) ACGGCGTCCGCAACCGGACGATAATTTTTCTGCTCTTCAACGAACTGCGCAAAATCGTGG AAACGG

TTCGGGTCCAGCAGACGCAGACGGGCGAAGTGGCTTTCCATCCCCAGCTGTTCCGGG GTCGCGGTC

AGCAGCAGAACGCCCGGCACGTGCTCTGCCAGTTGTTCAATGGCCTGATTCGAGAAA GAGTGTTG

ACTTGTGAGCGGATAACAATGATACTTAGATTCAATTGTGAGCGGATAACAATTTCA CACAGGCTA

GCG A ATTCG AGCTCCCTCT AG A A AT A ATTTTGTTT A ACTTT AAG A AGG AG AT AT ACC ATGGGC AGC

AGCT ACCC AT ACG ACGT ACC AG ATT ACGCTTCCG A AGTCG AGTTTTCCC ATG AGT ACTGG ATG AG A

CACGCATTGACTCTCGCAAAGAGGGCTCGAGATGAACGCGAGGTGCCCGTGGGGGCA GTACTCGT

GCTCAACAATCGCGTAATCGGCGAAGGTTGGAATAGGGCAATCGGACTCCACGACCC CACTGCAC

ATGCGGAAATCATGGCCCTTCGACAGGGAGGGCTTGTGATGCAGAATTATCGACTTA TCGATGCG

ACGCTGTACGTCACGTTTGAACCTTGCGTAATGTGCGCGGGAGCTATGATTCACTCC CGCATTGGA

CGAGTTGTATTCGGTGTTCGCAACGCCAAGACGGGTGCCGCAGGTTCACTGATGGAC GTGCTGCAT

TACCCAGGCATGAACCACCGGGTAGAAATCACAGAAGGCATATTGGCGGACGAATGT GCGGCGCT

GTTGTGTTACTTTTTTCGCATGCCCAGGCAGGTCTTTAACGCCCAGAAAAAAGCACA ATCCTCTAC

TGACTCTGGTGGTTCTTCTGGTGGTTCTAGCGGCAGCGAGACTCCCGGGACCTCAGA GTCCGCCAC

ACCCGAAAGTTCTGGTGGTTCTTCTGGTGGTTCTAGAGGATACCATATGAACACGAT TAACATCGC

TAAGAACGACTTCTCTGACATCGAACTGGCTGCTATCCCGTTCAACACTCTGGCTGA CCATTACGG

TGAGCGTTTAGCTCGCGAACAGTTGGCCCTTGAGCATGAGTCTTACGAGATGGGTGA AGCACGCTT

CCGCAAGATGTTTGAGCGTCAACTTAAAGCTGGTGAGGTTGCGGATAACGCTGCCGC CAAGCCTCT

CATCACTACCCTACTCCCTAAGATGATTGCACGCATCAACGACTGGTTTGAGGAAGT GAAAGCTAA

GCGCGGCAAGCGCCCGACAGCCTTCCAGTTCCTGCAAGAAATCAAGCCGGAAGCCGT AGCGTACA

TCACCATTAAGACCACTCTGGCTTGCCTAACCAGTGCTGACAATACAACCGTTCAGG CTGTAGCAA

GCGCAATCGGTCGGGCCATTGAGGACGAGGCTCGCTTCGGTCGTATCCGTGACCTTG AAGCTAAGC

ACTTCAAGAAAAACGTTGAGGAACAACTCAACAAGCGCGTAGGGCACGTCTACAAGA AAGCATTT

ATGCAAGTTGTCGAGGCTGACATGCTCTCTAAGGGTCTACTCGGTGGCGAGGCGTGG TCTTCGTGG

CATAAGGAAGACTCTATTCATGTAGGAGTACGCTGCATCGAGATGCTCATTGAGTCA ACCGGAAT

GGTTAGCTTACACCGCCAAAATGCTGGCGTAGTAGGTCAAGACTCTGAGACTATCGA ACTCGCACC

TGAATACGCTGAGGCTATCGCAACCCGTGCAGGTGCGCTGGCTGGCATCTCTCCGAT GTTCCAACC

TTGCGTAGTTCCTCCTAAGCCGTGGACTGGCATTACTGGTGGTGGCTATTGGGCTAA CGGTCGTCG

TCCTCTGGCGCTGGTGCGTACTCACAGTAAGAAAGCACTGATGCGCTACGAAGACGT TTACATGCC

TGAGGTGTACAAAGCGATTAACATTGCGCAAAACACCGCATGGAAAATCAACAAGAA AGTCCTAG

CGGTCGCCAACGTAATCACCAAGTGGAAGCATTGTCCGGTCGAGGACATCCCTGCGA TTGAGCGT

GAAGAACTCCCGATGAAACCGGAAGACATCGACATGAATCCTGAGGCTCTCACCGCG TGGAAACG

TGCTGCCGCTGCTGTGTACCGCAAGGACAAGGCTCGCAAGTCTCGCCGTATCAGCCT TGAGTTCAT

GCTTGAGCAAGCCAATAAGTTTGCTAACCATAAGGCCATCTGGTTCCCTTACAACAT GGACTGGCG

CGGTCGTGTTTACGCTGTGTCAATGTTCAACCCGCAAGGTAACGATATGACCAAAGG ACTGCTTAC

GCTGGCGAAAGGTAAACCAATCGGTAAGGAAGGTTACTACTGGCTGAAAATCCACGG TGCAAACT

GTGCGGGTGTCGATAAGGTTCCGTTCCCTGAGCGCATCAAGTTCATTGAGGAAAACC ACGAGAAC

ATCATGGCTTGCGCTAAGTCTCCACTGGAGAACACTTGGTGGGCTGAGCAAGATTCT CCGTTCTGC

TTCCTTGCGTTCTGCTTTGAGTACGCTGGGGTACAGCACCACGGCCTGAGCTATAAC TGCTCCCTTC

CGCTGGCGTTTGACGGGTCTTGCTCTGGCATCCAGCACTTCTCCGCGATGCTCCGAG ATGAGGTAG

GTGGTCGCGCGGTTAACTTGCTTCCTAGTGAAACCGTTCAGGACATCTACGGGATTG TTGCTAAGA

AAGTCAACGAGATTCTACAAGCAGACGCAATCAATGGGACCGATAACGAAGTAGTTA CCGTGACC

GATGAGAACACTGGTGAAATCTCTGAGAAAGTCAAGCTGGGCACTAAGGCACTGGCT GGTCAATG

GCTGGCTTACGGTGTTACTCGCAGTGTGACTAAGCGTTCAGTCATGACGCTGGCTTA CGGGTCCAA

AGAGTTCGGCTTCCGTCAACAAGTGCTGGAAGATACCATTCAGCCAGCTATTGATTC CGGCAAGGG

TCTGATGTTCACTCAGCCGAATCAGGCTGCTGGATACATGGCTAAGCTGATTTGGGA ATCTGTGAG

CGTGACGGTGGTAGCTGCGGTTGAAGCAATGAACTGGCTTAAGTCTGCTGCTAAGCT GCTGGCTGC

TGAGGTCAAAGATAAGAAGACTGGAGAGATTCTTCGCAAGCGTTGCGCTGTGCATTG GGTAACTC

CTGATGGTTTCCCTGTGTGGCAGGAATACAAGAAGCCTATTCAGACGCGCTTGAACC TGATGTTCC

TCGGTC AGTTCCGCTT AC AGCCT ACC ATT A AC ACC A AC A A AG AT AGCG AG ATTG ATGC AC AC A A A

C AGG AGTCTGGT ATCGCTCCT A ACTTTGT AC AC AGCC A AG ACGGT AGCC ACCTTCGT AAG ACTGT A

GTGTGGGCACACGAGAAGTACGGAATCGAATCTTTTGCACTGATTCACGACTCCTTC GGTACCATT

CCGGCTGACGCTGCGAACCTGTTCAAAGCAGTGCGCGAAACTATGGTTGACACATAT GAGTCTTGT

GATGTACTGGCTGATTTCTACGACCAGTTCGCTGACCAGTTGCACGAGTCTCAATTG GACAAAATG

CCAGCACTTCCGGCTAAAGGTAACTTGAACCTCCGTGACATCTTAGAGTCGGACTTC GCGTTCGCG

TAATCTAGAGTCGACCTGCAGGCATGCAAGCTTGGCTGTTTTGGCGGATGAGAGAAG ATTTTCAGT

TGAACGCCAGGCGCGGCAACGGGGTTATCAACTGCTGATTGCCTGCTCAGAAGATCA GCCAGACA

ACGAAATGCGGTGCATTGAGCACCTTTTACAGCGTCAGGTTGATGCCATTATTGTTT CGACGTCGT

TGCCTCCTGAGCATCCTTTTTATCAACGCTGGGCTAACGACCCGTTCCCGATTGTCG CGCTGG * tadA-GGS-T7 del araA-leu7697 insertion (SEQ ID NO: 90)

ACGGCGTCCGCAACCGGACGATAATTTTTCTGCTCTTCAACGAACTGCGCAAAATCGTGG AAACGG

TTCGGGTCCAGCAGACGCAGACGGGCGAAGTGGCTTTCCATCCCCAGCTGTTCCGGG GTCGCGGTC

AGCAGCAGAACGCCCGGCACGTGCTCTGCCAGTTGTTCAATGGCCTGATTCGAGAAA GAGTGTTG

ACTTGTGAGCGGATAACAATGATACTTAGATTCAATTGTGAGCGGATAACAATTTCA CACAGGCTA

GCG A ATTCG AGCTCCCTCT AG A A AT A ATTTTGTTT A ACTTT AAG A AGG AG AT AT ACC ATGGGC AGC

AGCT ACCC AT ACG ACGT ACC AG ATT ACGCTTCCG A AGTCG AGTTTTCCC ATG AGT ACTGG ATG AG A

CACGCATTGACTCTCGCAAAGAGGGCTCGAGATGAACGCGAGGTGCCCGTGGGGGCA GTACTCGT

GCTCAACAATCGCGTAATCGGCGAAGGTTGGAATAGGGCAATCGGACTCCACGACCC CACTGCAC

ATGCGGAAATCATGGCCCTTCGACAGGGAGGGCTTGTGATGCAGAATTATCGACTTA TCGATGCG

ACGCTGTACGTCACGTTTGAACCTTGCGTAATGTGCGCGGGAGCTATGATTCACTCC CGCATTGGA

CGAGTTGTATTCGGTGTTCGCAACGCCAAGACGGGTGCCGCAGGTTCACTGATGGAC GTGCTGCAT

TACCCAGGCATGAACCACCGGGTAGAAATCACAGAAGGCATATTGGCGGACGAATGT GCGGCGCT

GTTGTGTTACTTTTTTCGCATGCCCAGGCAGGTCTTTAACGCCCAGAAAAAAGCACA ATCCTCTAC

TGACGGCGGTAGCGGAGGGAGTGGCGGTAGCGGAGGGAGTGGGAGCTCAAGAGGATA CCATATG

AACACGATTAACATCGCTAAGAACGACTTCTCTGACATCGAACTGGCTGCTATCCCG TTCAACACT

CTGGCTGACCATTACGGTGAGCGTTTAGCTCGCGAACAGTTGGCCCTTGAGCATGAG TCTTACGAG

ATGGGTGAAGCACGCTTCCGCAAGATGTTTGAGCGTCAACTTAAAGCTGGTGAGGTT GCGGATAA

CGCTGCCGCCAAGCCTCTCATCACTACCCTACTCCCTAAGATGATTGCACGCATCAA CGACTGGTT

TGAGGAAGTGAAAGCTAAGCGCGGCAAGCGCCCGACAGCCTTCCAGTTCCTGCAAGA AATCAAGC

CGGAAGCCGTAGCGTACATCACCATTAAGACCACTCTGGCTTGCCTAACCAGTGCTG ACAATACAA

CCGTTCAGGCTGTAGCAAGCGCAATCGGTCGGGCCATTGAGGACGAGGCTCGCTTCG GTCGTATCC

GTGACCTTGAAGCTAAGCACTTCAAGAAAAACGTTGAGGAACAACTCAACAAGCGCG TAGGGCAC

GTCTACAAGAAAGCATTTATGCAAGTTGTCGAGGCTGACATGCTCTCTAAGGGTCTA CTCGGTGGC

GAGGCGTGGTCTTCGTGGCATAAGGAAGACTCTATTCATGTAGGAGTACGCTGCATC GAGATGCTC

ATTGAGTCAACCGGAATGGTTAGCTTACACCGCCAAAATGCTGGCGTAGTAGGTCAA GACTCTGA

GACTATCGAACTCGCACCTGAATACGCTGAGGCTATCGCAACCCGTGCAGGTGCGCT GGCTGGCAT

CTCTCCGATGTTCCAACCTTGCGTAGTTCCTCCTAAGCCGTGGACTGGCATTACTGG TGGTGGCTAT

TGGGCTAACGGTCGTCGTCCTCTGGCGCTGGTGCGTACTCACAGTAAGAAAGCACTG ATGCGCTAC

GAAGACGTTTACATGCCTGAGGTGTACAAAGCGATTAACATTGCGCAAAACACCGCA TGGAAAAT

CAACAAGAAAGTCCTAGCGGTCGCCAACGTAATCACCAAGTGGAAGCATTGTCCGGT CGAGGACA

TCCCTGCGATTGAGCGTGAAGAACTCCCGATGAAACCGGAAGACATCGACATGAATC CTGAGGCT

CTCACCGCGTGGAAACGTGCTGCCGCTGCTGTGTACCGCAAGGACAAGGCTCGCAAG TCTCGCCGT

ATCAGCCTTGAGTTCATGCTTGAGCAAGCCAATAAGTTTGCTAACCATAAGGCCATC TGGTTCCCT

TACAACATGGACTGGCGCGGTCGTGTTTACGCTGTGTCAATGTTCAACCCGCAAGGT AACGATATG

ACCAAAGGACTGCTTACGCTGGCGAAAGGTAAACCAATCGGTAAGGAAGGTTACTAC TGGCTGAA

AATCCACGGTGCAAACTGTGCGGGTGTCGATAAGGTTCCGTTCCCTGAGCGCATCAA GTTCATTGA

GGAAAACCACGAGAACATCATGGCTTGCGCTAAGTCTCCACTGGAGAACACTTGGTG GGCTGAGC

AAGATTCTCCGTTCTGCTTCCTTGCGTTCTGCTTTGAGTACGCTGGGGTACAGCACC ACGGCCTGAG

CTATAACTGCTCCCTTCCGCTGGCGTTTGACGGGTCTTGCTCTGGCATCCAGCACTT CTCCGCGATG

CTCCGAGATGAGGTAGGTGGTCGCGCGGTTAACTTGCTTCCTAGTGAAACCGTTCAG GACATCTAC

GGGATTGTTGCTAAGAAAGTCAACGAGATTCTACAAGCAGACGCAATCAATGGGACC GATAACGA

AGTAGTTACCGTGACCGATGAGAACACTGGTGAAATCTCTGAGAAAGTCAAGCTGGG CACTAAGG

CACTGGCTGGTCAATGGCTGGCTTACGGTGTTACTCGCAGTGTGACTAAGCGTTCAG TCATGACGC

TGGCTTACGGGTCCAAAGAGTTCGGCTTCCGTCAACAAGTGCTGGAAGATACCATTC AGCCAGCTA

TTGATTCCGGCAAGGGTCTGATGTTCACTCAGCCGAATCAGGCTGCTGGATACATGG CTAAGCTGA

TTTGGGAATCTGTGAGCGTGACGGTGGTAGCTGCGGTTGAAGCAATGAACTGGCTTA AGTCTGCTG

CTAAGCTGCTGGCTGCTGAGGTCAAAGATAAGAAGACTGGAGAGATTCTTCGCAAGC GTTGCGCT

GTGCATTGGGTAACTCCTGATGGTTTCCCTGTGTGGCAGGAATACAAGAAGCCTATT CAGACGCGC

TTG A ACCTG ATGTTCCTCGGTC AGTTCCGCTT AC AGCCT ACC ATT A AC ACC A AC A A AG AT AGCG AG

ATTGATGCACACAAACAGGAGTCTGGTATCGCTCCTAACTTTGTACACAGCCAAGAC GGTAGCCAC

CTTCGTAAGACTGTAGTGTGGGCACACGAGAAGTACGGAATCGAATCTTTTGCACTG ATTCACGAC

TCCTTCGGTACCATTCCGGCTGACGCTGCGAACCTGTTCAAAGCAGTGCGCGAAACT ATGGTTGAC

ACATATGAGTCTTGTGATGTACTGGCTGATTTCTACGACCAGTTCGCTGACCAGTTG CACGAGTCT

CAATTGGACAAAATGCCAGCACTTCCGGCTAAAGGTAACTTGAACCTCCGTGACATC TT AG AGTCG

GACTTCGCGTTCGCGTAATCTAGAGTCGACCTGCAGGCATGCAAGCTTGGCTGTTTT GGCGGATGA GAGAAGATTTTCAGTTGAACGCCAGGCGCGGCAACGGGGTTATCAACTGCTGATTGCCTG CTCAG

AAGATCAGCCAGACAACGAAATGCGGTGCATTGAGCACCTTTTACAGCGTCAGGTTG ATGCCATT

ATTGTTTCGACGTCGTTGCCTCCTGAGCATCCTTTTTATCAACGCTGGGCTAACGAC CCGTTCCCGA

TTGTCGCGCTGG

* BAC-KanStop-TetStop (SEQ ID NO: 91)

AC A ATT A ATC ATCGGCTCG A AGCTTGTTG AC A ATT A ATC ATCGGC AT AGT AT ATCGGC AT AGT AT A

ATACGACAAGGTGAGGAACTAAACCATGGGATCGGCCATTGAACAAGATGGATTGCA CGCAGGTT

CTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCG GCTGCTCTG

ATGCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCG ACCTGTCCG

GTGCCCTGAATGAACTGCAGGACGAGGCAGCGCGGCTATCGTAGCTGGCCACGACGG GCGTTCCT

TGCGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGC GAAGTGCC

GGGGCAGGATCTCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGC TGATGCAAT

GCGGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACA TCGCATCGA

GCGAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGA GCATCAGG

GGCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGCGCATGCCCGACGGCGATG ATCTCGTC

GTGACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCT GGATTCATC

GACTGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGT GATATTGCT

GAAGAGCTTGGCGGCGAATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCT CCCGATTCG

CAGCGCATCGCCTTCTATCGCCTTCTTGACGAGTTCTTCTGAGGGGATCAATTCTCT AGAGCTTAAT

TAACGCAGCCTGAATGGCGAATAGGGATCCTTGACAGCTTATCATCGATAAGCTTTA ATGCGGTAG

TTTATCACAGTTGCTAACGCAGTCAGGCACCGTGTATGAATAGTTCGACAAAGATCG CATTGGTAA

TTACGTTACTCGATGCCATGGGGATTGGCCTTATCATGCCAGTCTTGCCAACGTTAT TACGTGAATT

TATTGCTTCGGAAGATATCGCTAACCACTTTGGCGTATTGCTTGCACTTTATGCGTT AATGCAGGTT

ATCTTTGCTCCTTAGCTTGGAAAAATGTCTGACCGATTTGGTCGGCGCCCAGTGCTG TTGTTGTCAT

TAATAGGCGCATCGCTGGATTACTTATTGCTGGCTTTTTCAAGTGCGCTTTGGATGC TGTATTTAGG

CCGTTTGCTTTCAGGGATCACAGGAGCTACTGGGGCTGTCGCGGCATCGGTCATTGC CGATACCAC

CTCAGCTTCTCAACGCGTGAAGTGGTTCGGTTGGTTAGGGGCAAGTTTTGGGCTTGG TTTAATAGC

GGGGCCTATTATTGGTGGTTTTGCAGGAGAGATTTCACCGCATAGTCCCTTTTTTAT CGCTGCGTTG

CTAAATATTGTCACTTTCCTTGTGGTTATGTTTTGGTTCCGTGAAACCAAAAATACA CGTGATAATA

C AG AT ACCG A AGT AGGGGTTG AG ACGC A ATCG A ATTCGGT AT AC ATC ACTTT ATTT AA A ACG ATGC

CCATTTTGTTGATTATTTATTTTTCAGCGCAATTGATAGGCCAAATTCCCGCAACGG TGTGGGTGCT

ATTT ACCG AAAATCGTTTTGGATGGAATAGCATGATGGTTGGCTTTTCATTAGCGGGTCTTGGTCTT

TTACACTCAGTATTCCAAGCCTTTGTGGCAGGAAGAATAGCCACTAAATGGGGCGAA AAAACGGC

AGTACTGCTCGGATTTATTGCAGATAGTAGTGCATTTGCCTTTTTAGCGTTTATATC TGAAGGTTGG

TTAGTTTTCCCTGTTTTAATTTTATTGGCTGGTGGTGGGATCGCTTTACCTGCATTA CAGGGAGTGA

TGTCTATCCAAACAAAGAGTCATCAGCAAGGTGCTTTACAGGGATTATTGGTGAGCC TTACCAATG

CAACCGGTGTTATTGGCCCATTACTGTTTGCTGTTATTTATAATCATTCACTACCAA TTTGGGATGG

CTGGATTTGGATTATTGGTTTAGCGTTTTACTGTATTATTATCCTGCTATCGATGAC CTTCATGTTAA

CCCCTCAAGCTCAGGGGAGTAAACAGGAGACAAGTGCTTAGTGATCCAATTCTTGAA GACGAAAG

GGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAG ACGTCAGGTG

GCACTTTTCGGGGAAATGTGCCCGGTTAACGTGCCGGCACGGCCTGGGTAACCAGGT ATTTTGTCC

ACATAACCGTGCGCAAAATGTTGTGGATAAGCAGGACACAGCAGCAATCCACAGCAG GCATACAA

CCGCACACCGAGGTTACTCCGTTCTACAGGTTACGACGACATGTCAATACTTGCCCT TGACAGGCA

TTGATGGAATCGTAGTCTCACGCTGATAGTCTGATCGACAATACAAGTGGGACCGTG GTCCCAGAC

CGATAATCAGACCGACAACACGAGTGGGATCGTGGTCCCAGACTAATAATCAGACCG ACGATACG

AGTGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTGGGACCGTGGT TCCAGACT

AATAATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGA CGATACGA

GTGGGACCATGGTCCCAGACTAATAATCAGACCGACGATACGAGTGGGACCGTGGTC CCAGTCTG

ATTATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGAC GATACGAG

TGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTGGGACCGTGGTCC CAGTCTGA

TTATCAGACCGACGATACAAGTGGAACAGTGGGCCCAGAGAGAATATTCAGGCCAGT TATGCTTT

CTGGCCTGTAACAAAGGACATTAAGTAAAGACAGATAAACGTAGACTAAAACGTGGT CGCATCAG

GGTGCTGGCTTTTCAAGTTCCTTAAGAATGGCCTCAATTTTCTCTATACACTCAGTT GGAACACGAG

ACCTGTCC AGGTT AAGC ACC ATTTT ATCGCCCTT AT AC A AT ACTGTCGCTCC AGG AGC A A ACTG AT

GTCGTGAGCTTAAACTAGTTCTTGATGCAGATGACGTTTTAAGCACAGAAGTTAAAA GAGTGATAA

CTTCTTCAGCTTCAAATATCACCCCAGCTTTTTTCTGCTCATGAAGGTTAGATGCCT GCTGCTTAAG TAATTCCTCTTTATCTGTAAAGGCTTTTTGAAGTGCATCACCTGACCGGGCAGATAGTTC ACCGGG

GTGAGAAAAAAGAGCAACAACTGATTTAGGCAATTTGGCGGTGTTGATACAGCGGGT AATAATCT

TACGTGAAATATTTTCCGCATCAGCCAGCGCAGAAATATTTCCAGCAAATTCATTCT GCAATCGGC

TTGCATAACGCTGACCACGTTCATAAGCACTTGTTGGGCGATAATCGTTACCCAATC TGGATAATG

CAGCCATCTGCTCATCATCCAGCTCGCCAACCAGAACACGATAATCACTTTCGGTAA GTGCAGCAG

CTTTACGACGGCGACTCCCATCGGCAATTTCTATGACACCAGATACTCTTCGACCGA ACGCCGGTG

TCTGTTGACCAGTCAGTAGAAAAGAAGGGATGAGATCATCCAGTGCGTCCTCAGTAA GCAGCTCC

TGGTCACGTTCATTACCTGACCATACCCGAGAGGTCTTCTCAACACTATCACCCCGG AGCACTTCA

AG AGT A A ACTTC AC ATCCCG ACC AC AT AC AGGC A A AGT A ATGGC ATT ACCGCG AGCC ATT ACTCCT

ACGCGCGCAATTAACGAATCCACCATCGGGGCAGCTGGTGTCGATAACGAAGTATCT TCAACCGG

TTGAGTATTGAGCGTATGTTTTGGAATAACAGGCGCACGCTTCATTATCTAATCTCC CAGCGTGGTT

TAATCAGACGATCGAAAATTTCATTGCAGACAGGTTCCCAAATAGAAAGAGCATTTC TCCAGGCA

CCAGTTGAAGAGCGTTGATCAATGGCCTGTTCAAAAACAGTTCTCATCCGGATCTGA CCTTTACCA

ACTTCATCCGTTTCACGTACAACATTTTTTAGAACCATGCTTCCCCAGGCATCCCGA ATTTGCTCCT

CC ATCC ACGGGG ACTG AG AGCC ATT ACT ATTGCTGT ATTTGGT AAGC A A A AT ACGT AC ATC AGGCT

CGAACCCTTTAAGATCAACGTTCTTGAGCAGATCACGAAGCATATCGAAAAACTGCA GTGCGGAG

GTGTAGTCAAACAACTCAGCAGGCGTGGGAACAATCAGCACATCAGCAGCACATACG ACATTAAT

CGTGCCGATACCCAGGTTAGGCGCGCTGTCAATAACTATGACATCATAGTCATGAGC AACAGTTTC

AATGGCCAGTCGGAGCATCAGGTGTGGATCGGTGGGCAGTTTACCTTCATCAAATTT GCCCATTAA

CTCAGTTTCAATACGGTGCAGAGCCAGACAGGAAGGAATAATGTCAAGCCCCGGCCA GCAAGTGG

GCTTTATTGCATAAGTGACATCGTCCTTTTCCCCAAGATAGAAAGGCAGGAGAGTGT CTTCTGCAT

GAATATGAAGATCTGGTACCCATCCGTGATACATTGAGGCTGTTCCCTGGGGGTCGT TACCTTCCA

CGAGCAAAACACGTAGCCCCTTCAGAGCCAGATCCTGAGCAAGATGAACAGAAACTG AGGTTTTG

TAAACGCCACCTTTATGGGCAGCAACCCCGATCACCGGTGGAAATACGTCTTCAGCA CGTCGCAAT

CGCGTACCAAACACATCACGCATATGATTAATTTGTTCAATTGTATAACCAACACGT TGCTCAACC

CGTCCTCGAATTTCCATATCCGGGTGCGGTAGTCGCCCTGCTTTCTCGGCATCTCTG ATAGCCTGAG

AAGAAACCCCAACTAAATCCGCTGCTTCACCTATTCTCCAGCGCCGGGTTATTTTCC TCGCTTCCGG

GCTGTCATCATTAAACTGTGCAATGGCGATAGCCTTCGTCATTTCATGACCAGCGTT TATGCACTG

GTTAAGTGTTTCCATGAGTTTCATTCTGAACATCCTTTAATCATTGCTTTGCGTTTT TTTATTAAATC

TTGCAATTTACTGCAAAGCAACAACAAAATCGCAAAGTCATCAAAAAACCGCAAAGT TGTTTAAA

AT A AG AGC A AC ACT AC AAA AGG AG AT A AG A AG AGC AC AT ACCTC AGTC ACTTATT ATC ACT AGCG

CTCGCCGCAGCCGTGTAACCGAGCATAGCGAGCGAACTGGCGAGGAAGCAAAGAAGA ACTGTTCT

GTCAGATAGCTCTTACGCTCAGCGCAAGAAGAAATATCCACCGTGGGAAAAACTCCA GGTAGAGG

TACACACGCGGATAGCCAATTCAGAGTAATAAACTGTGATAATCAACCCTCATCAAT GATGACGA

ACTAACCCCCGATATCAGGTCACATGACGAAGGGAAAGAGAAGGAAATCAACTGTGA CAAACTGC

CCTCAAATTTGGCTTCCTTAAAAATTACAGTTCAAAAAGTATGAGAAAATCCATGCA GGCTGAAGG

AAACAGCAAAACTGTGACAAATTACCCTCAGTAGGTCAGAACAAATGTGACGAACCA CCCTCAAA

TCTGTGACAGATAACCCTCAGACTATCCTGTCGTCATGGAAGTGATATCGCGGAAGG AAAATACG

ATATGAGTCGTCTGGCGGCCTTTCTTTTTCTCAATGTATGAGAGGCGCATTGGAGTT CTGCTGTTGA

TCTCATTAACACAGACCTGCAGGAAGCGGCGGCGGAAGTCAGGCATACGCTGGTAAC TTTGAGGC

AGCTGGTAACGCTCTATGATCCAGTCGATTTTCAGAGAGACGATGCCTGAGCCATCC GGCTTACGA

TACTGACACAGGGATTCGTATAAACGCATGGCATACGGATTGGTGATTTCTTTTGTT TCACTAAGC

CGAAACTGCGTAAACCGGTTCTGTAACCCGATAAAGAAGGGAATGAGATATGGGTTG ATATGTAC

ACTGTAAAGCCCTCTGGATGGACTGTGCGCACGTTTGATAAACCAAGGAAAAGATTC ATAGCCTTT

TTCATCGCCGGCATCCTCTTCAGGGCGATAAAAAACCACTTCCTTCCCCGCGAAACT CTTCAATGC

CTGCCGT AT ATCCTT ACTGGCTTCCGC AG AGGTC A ATCCG A AT ATTTC AGC AT ATTT AGC A AC ATG

GATCTCGCAGATACCGTCATGTTCCTGTAGGGTGCCATCAGATTTTCTGATCTGGTC AACGAACAG

ATACAGCATACGTTTTTGATCCCGGGAGAGACTATATGCCGCCTCAGTGAGGTCGTT TGACTGGAC

GATTCGCGGGCTATTTTTACGTTTCTTGTGATTGATAACCGCTGTTTCCGCCATGAC AGATCCATGT

G A AGTGTG AC A AGTTTTT AG ATTGTC AC ACT A A AT A A A A A AG AGTC A AT A AGC AGGG AT A ACTTT

GTGAAAAAACAGCTTCTTCTGAGGGCAATTTGTCACAGGGTTAAGGGCAATTTGTCA CAGACAGG

ACTGTCATTTGAGGGTGATTTGTCACACTGAAAGGGCAATTTGTCACAACACCTTCT CTAGAACCA

GC ATGG AT A A AGGCCT AC A AGGCGCTCT AA A A A AG A AG ATCT A A A A ACT AT A A A A A A A AT A ATT A

TAAAAATATCCCCGTGGATAAGTGGATAACCCCAAGGGAAGTTTTTTCAGGCATCGT GTGTAAGCA

GAATATATAAGTGCTGTTCCCTGGTGCTTCCTCGCTCACTCGAGCTACGGGGTCTGA CGCTCAGTG

GAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCAC CTAGATCCT

TTT AA ATT AA A A ATG A AGTTTT AA ATC A ATCT A A AGT AT AT ATG AGT A A ACTTGGTCTG AC AGTT A

CCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCAT AGTTGCCTGA

CTGCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCT GCAATGATA CCGCGGGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGG GCCGA

GCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCG GGAAGCTAG

AGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCAT CGTGGTGTC

ACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGT TACATGATC

CCCCATGTTGTGAAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAG TAAGTTGGC

CGCAGTGTTATCACTCATGCTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCC ATCCGTAAGA

TGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGG CGACCGAGT

TGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAA GTGCTCATC

ATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCC AGTTCGATG

TAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCT GGGTGAGCAA

AAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAA TACTCAT

ACTCTTCCTTTTTC A AT ATT ATTG AAGC ATTT ATC AGGGTT ATTGTCTC ATG AGCGG AT AC AT ATTT

GAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTG CCACCTGG

CGGCCGCTTG

* B AC -T7 - KanS top-T etS top (SEQ ID NO: 92)

AC A ATT A ATC ATCGGCTCG A AGCTTGTTG AC A ATT A ATC ATCGGC AT AGT AT ATCGGC AT AGT AT A

ATACGACAAGGTGAGGAACTAAACCATGGGATCGGCCATTGAACAAGATGGATTGCA CGCAGGTT

CTCCGGCCGCTTGGGTGGAGAGGCTATTCGGCTATGACTGGGCACAACAGACAATCG GCTGCTCTG

ATGCCGCCGTGTTCCGGCTGTCAGCGCAGGGGCGCCCGGTTCTTTTTGTCAAGACCG ACCTGTCCG

GTGCCCTGAATGAACTGCAGGACGAGGCAGCGCGGCTATCGTAGCTGGCCACGACGG GCGTTCCT

TGCGCAGCTGTGCTCGACGTTGTCACTGAAGCGGGAAGGGACTGGCTGCTATTGGGC GAAGTGCC

GGGGCAGGATCTCCTGTCATCTCACCTTGCTCCTGCCGAGAAAGTATCCATCATGGC TGATGCAAT

GCGGCGGCTGCATACGCTTGATCCGGCTACCTGCCCATTCGACCACCAAGCGAAACA TCGCATCGA

GCGAGCACGTACTCGGATGGAAGCCGGTCTTGTCGATCAGGATGATCTGGACGAAGA GCATCAGG

GGCTCGCGCCAGCCGAACTGTTCGCCAGGCTCAAGGCGCGCATGCCCGACGGCGATG ATCTCGTC

GTGACCCATGGCGATGCCTGCTTGCCGAATATCATGGTGGAAAATGGCCGCTTTTCT GGATTCATC

GACTGTGGCCGGCTGGGTGTGGCGGACCGCTATCAGGACATAGCGTTGGCTACCCGT GATATTGCT

GAAGAGCTTGGCGGCGAATGGGCTGACCGCTTCCTCGTGCTTTACGGTATCGCCGCT CCCGATTCG

CAGCGCATCGCCTTCTATCGCCTTCTTGACGAGTTCTTCTGAGGGGATCAATTCTCT AGAGCTTAAT

TAACGCAGCCTGAATGGCGAATAGGGATCCTTGACAGCTTATCATCGATAAGCTTTA ATGCGGTAG

TTTATCACAGTTGCTAACGCAGTCAGGCACCGTGTATGAATAGTTCGACAAAGATCG CATTGGTAA

TTACGTTACTCGATGCCATGGGGATTGGCCTTATCATGCCAGTCTTGCCAACGTTAT TACGTGAATT

TATTGCTTCGGAAGATATCGCTAACCACTTTGGCGTATTGCTTGCACTTTATGCGTT AATGCAGGTT

ATCTTTGCTCCTTAGCTTGGAAAAATGTCTGACCGATTTGGTCGGCGCCCAGTGCTG TTGTTGTCAT

TAATAGGCGCATCGCTGGATTACTTATTGCTGGCTTTTTCAAGTGCGCTTTGGATGC TGTATTTAGG

CCGTTTGCTTTCAGGGATCACAGGAGCTACTGGGGCTGTCGCGGCATCGGTCATTGC CGATACCAC

CTCAGCTTCTCAACGCGTGAAGTGGTTCGGTTGGTTAGGGGCAAGTTTTGGGCTTGG TTTAATAGC

GGGGCCTATTATTGGTGGTTTTGCAGGAGAGATTTCACCGCATAGTCCCTTTTTTAT CGCTGCGTTG

CTAAATATTGTCACTTTCCTTGTGGTTATGTTTTGGTTCCGTGAAACCAAAAATACA CGTGATAATA

C AG AT ACCG A AGT AGGGGTTG AG ACGC A ATCG A ATTCGGT AT AC ATC ACTTT ATTT AA A ACG ATGC

CCATTTTGTTGATTATTTATTTTTCAGCGCAATTGATAGGCCAAATTCCCGCAACGG TGTGGGTGCT

ATTT ACCG AAAATCGTTTTGGATGGAATAGCATGATGGTTGGCTTTTCATTAGCGGGTCTTGGTCTT

TTACACTCAGTATTCCAAGCCTTTGTGGCAGGAAGAATAGCCACTAAATGGGGCGAA AAAACGGC

AGTACTGCTCGGATTTATTGCAGATAGTAGTGCATTTGCCTTTTTAGCGTTTATATC TGAAGGTTGG

TTAGTTTTCCCTGTTTTAATTTTATTGGCTGGTGGTGGGATCGCTTTACCTGCATTA CAGGGAGTGA

TGTCTATCCAAACAAAGAGTCATCAGCAAGGTGCTTTACAGGGATTATTGGTGAGCC TTACCAATG

CAACCGGTGTTATTGGCCCATTACTGTTTGCTGTTATTTATAATCATTCACTACCAA TTTGGGATGG

CTGGATTTGGATTATTGGTTTAGCGTTTTACTGTATTATTATCCTGCTATCGATGAC CTTCATGTTAA

CCCCTCAAGCTCAGGGGAGTAAACAGGAGACAAGTGCTTAGTGATCCAATTCTTGAA GACGAAAG

GGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAG ACGTCAGGTG

GCACTTTTCGGGGAAATGTGCCCGGTTAACGTGCCGGCACGGCCTGGGTAACCAGGT ATTTTGTCC

ACATAACCGTGCGCAAAATGTTGTGGATAAGCAGGACACAGCAGCAATCCACAGCAG GCATACAA

CCGCACACCGAGGTTACTCCGTTCTACAGGTTACGACGACATGTCAATACTTGCCCT TGACAGGCA

TTGATGGAATCGTAGTCTCACGCTGATAGTCTGATCGACAATACAAGTGGGACCGTG GTCCCAGAC

CGATAATCAGACCGACAACACGAGTGGGATCGTGGTCCCAGACTAATAATCAGACCG ACGATACG

AGTGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTGGGACCGTGGT TCCAGACT AATAATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGACGA TACGA

GTGGGACCATGGTCCCAGACTAATAATCAGACCGACGATACGAGTGGGACCGTGGTC CCAGTCTG

ATTATCAGACCGACGATACGAGTGGGACCGTGGTCCCAGACTAATAATCAGACCGAC GATACGAG

TGGGACCGTGGTCCCAGACTAATAATCAGACCGACGATACGAGTGGGACCGTGGTCC CAGTCTGA

TTATCAGACCGACGATACAAGTGGAACAGTGGGCCCAGAGAGAATATTCAGGCCAGT TATGCTTT

CTGGCCTGTAACAAAGGACATTAAGTAAAGACAGATAAACGTAGACTAAAACGTGGT CGCATCAG

GGTGCTGGCTTTTCAAGTTCCTTAAGAATGGCCTCAATTTTCTCTATACACTCAGTT GGAACACGAG

ACCTGTCC AGGTT AAGC ACC ATTTT ATCGCCCTT AT AC A AT ACTGTCGCTCC AGG AGC A A ACTG AT

GTCGTGAGCTTAAACTAGTTCTTGATGCAGATGACGTTTTAAGCACAGAAGTTAAAA GAGTGATAA

CTTCTTCAGCTTCAAATATCACCCCAGCTTTTTTCTGCTCATGAAGGTTAGATGCCT GCTGCTTAAG

TAATTCCTCTTTATCTGTAAAGGCTTTTTGAAGTGCATCACCTGACCGGGCAGATAG TTCACCGGG

GTGAGAAAAAAGAGCAACAACTGATTTAGGCAATTTGGCGGTGTTGATACAGCGGGT AATAATCT

TACGTGAAATATTTTCCGCATCAGCCAGCGCAGAAATATTTCCAGCAAATTCATTCT GCAATCGGC

TTGCATAACGCTGACCACGTTCATAAGCACTTGTTGGGCGATAATCGTTACCCAATC TGGATAATG

CAGCCATCTGCTCATCATCCAGCTCGCCAACCAGAACACGATAATCACTTTCGGTAA GTGCAGCAG

CTTTACGACGGCGACTCCCATCGGCAATTTCTATGACACCAGATACTCTTCGACCGA ACGCCGGTG

TCTGTTGACCAGTCAGTAGAAAAGAAGGGATGAGATCATCCAGTGCGTCCTCAGTAA GCAGCTCC

TGGTCACGTTCATTACCTGACCATACCCGAGAGGTCTTCTCAACACTATCACCCCGG AGCACTTCA

AG AGT A A ACTTC AC ATCCCG ACC AC AT AC AGGC A A AGT A ATGGC ATT ACCGCG AGCC ATT ACTCCT

ACGCGCGCAATTAACGAATCCACCATCGGGGCAGCTGGTGTCGATAACGAAGTATCT TCAACCGG

TTGAGTATTGAGCGTATGTTTTGGAATAACAGGCGCACGCTTCATTATCTAATCTCC CAGCGTGGTT

TAATCAGACGATCGAAAATTTCATTGCAGACAGGTTCCCAAATAGAAAGAGCATTTC TCCAGGCA

CCAGTTGAAGAGCGTTGATCAATGGCCTGTTCAAAAACAGTTCTCATCCGGATCTGA CCTTTACCA

ACTTCATCCGTTTCACGTACAACATTTTTTAGAACCATGCTTCCCCAGGCATCCCGA ATTTGCTCCT

CCATCCACGGGG ACTG AG AGCC ATT ACT ATTGCTGT ATTTGGT AAGC A A A AT ACGT AC ATC AGGCT

CGAACCCTTTAAGATCAACGTTCTTGAGCAGATCACGAAGCATATCGAAAAACTGCA GTGCGGAG

GTGTAGTCAAACAACTCAGCAGGCGTGGGAACAATCAGCACATCAGCAGCACATACG ACATTAAT

CGTGCCGATACCCAGGTTAGGCGCGCTGTCAATAACTATGACATCATAGTCATGAGC AACAGTTTC

AATGGCCAGTCGGAGCATCAGGTGTGGATCGGTGGGCAGTTTACCTTCATCAAATTT GCCCATTAA

CTCAGTTTCAATACGGTGCAGAGCCAGACAGGAAGGAATAATGTCAAGCCCCGGCCA GCAAGTGG

GCTTTATTGCATAAGTGACATCGTCCTTTTCCCCAAGATAGAAAGGCAGGAGAGTGT CTTCTGCAT

GAATATGAAGATCTGGTACCCATCCGTGATACATTGAGGCTGTTCCCTGGGGGTCGT TACCTTCCA

CGAGCAAAACACGTAGCCCCTTCAGAGCCAGATCCTGAGCAAGATGAACAGAAACTG AGGTTTTG

TAAACGCCACCTTTATGGGCAGCAACCCCGATCACCGGTGGAAATACGTCTTCAGCA CGTCGCAAT

CGCGTACCAAACACATCACGCATATGATTAATTTGTTCAATTGTATAACCAACACGT TGCTCAACC

CGTCCTCGAATTTCCATATCCGGGTGCGGTAGTCGCCCTGCTTTCTCGGCATCTCTG ATAGCCTGAG

AAGAAACCCCAACTAAATCCGCTGCTTCACCTATTCTCCAGCGCCGGGTTATTTTCC TCGCTTCCGG

GCTGTCATCATTAAACTGTGCAATGGCGATAGCCTTCGTCATTTCATGACCAGCGTT TATGCACTG

GTTAAGTGTTTCCATGAGTTTCATTCTGAACATCCTTTAATCATTGCTTTGCGTTTT TTTATTAAATC

TTGCAATTTACTGCAAAGCAACAACAAAATCGCAAAGTCATCAAAAAACCGCAAAGT TGTTTAAA

AT A AG AGC A AC ACT AC A A A AGG AG AT A AG A AG AGC AC AT ACCTC AGTC ACTTATT ATC ACT AGCG

CTCGCCGCAGCCGTGTAACCGAGCATAGCGAGCGAACTGGCGAGGAAGCAAAGAAGA ACTGTTCT

GTCAGATAGCTCTTACGCTCAGCGCAAGAAGAAATATCCACCGTGGGAAAAACTCCA GGTAGAGG

TACACACGCGGATAGCCAATTCAGAGTAATAAACTGTGATAATCAACCCTCATCAAT GATGACGA

ACTAACCCCCGATATCAGGTCACATGACGAAGGGAAAGAGAAGGAAATCAACTGTGA CAAACTGC

CCTCAAATTTGGCTTCCTTAAAAATTACAGTTCAAAAAGTATGAGAAAATCCATGCA GGCTGAAGG

AAACAGCAAAACTGTGACAAATTACCCTCAGTAGGTCAGAACAAATGTGACGAACCA CCCTCAAA

TCTGTGACAGATAACCCTCAGACTATCCTGTCGTCATGGAAGTGATATCGCGGAAGG AAAATACG

ATATGAGTCGTCTGGCGGCCTTTCTTTTTCTCAATGTATGAGAGGCGCATTGGAGTT CTGCTGTTGA

TCTCATTAACACAGACCTGCAGGAAGCGGCGGCGGAAGTCAGGCATACGCTGGTAAC TTTGAGGC

AGCTGGTAACGCTCTATGATCCAGTCGATTTTCAGAGAGACGATGCCTGAGCCATCC GGCTTACGA

TACTGACACAGGGATTCGTATAAACGCATGGCATACGGATTGGTGATTTCTTTTGTT TCACTAAGC

CGAAACTGCGTAAACCGGTTCTGTAACCCGATAAAGAAGGGAATGAGATATGGGTTG ATATGTAC

ACTGTAAAGCCCTCTGGATGGACTGTGCGCACGTTTGATAAACCAAGGAAAAGATTC ATAGCCTTT

TTCATCGCCGGCATCCTCTTCAGGGCGATAAAAAACCACTTCCTTCCCCGCGAAACT CTTCAATGC

CTGCCGT AT ATCCTT ACTGGCTTCCGC AG AGGTC A ATCCG A AT ATTTC AGC AT ATTT AGC A AC ATG

GATCTCGCAGATACCGTCATGTTCCTGTAGGGTGCCATCAGATTTTCTGATCTGGTC AACGAACAG

ATACAGCATACGTTTTTGATCCCGGGAGAGACTATATGCCGCCTCAGTGAGGTCGTT TGACTGGAC

GATTCGCGGGCTATTTTTACGTTTCTTGTGATTGATAACCGCTGTTTCCGCCATGAC AGATCCATGT G A AGTGTG AC A AGTTTTT AG ATTGTC AC ACT A A AT A A A A A AG AGTC A AT A AGC AGGG AT A ACTTT

GTGAAAAAACAGCTTCTTCTGAGGGCAATTTGTCACAGGGTTAAGGGCAATTTGTCA CAGACAGG

ACTGTCATTTGAGGGTGATTTGTCACACTGAAAGGGCAATTTGTCACAACACCTTCT CTAGAACCA

GC ATGG AT A A AGGCCT AC A AGGCGCTCT AA A A A AG A AG ATCT A A A A ACT AT A A A A A A A AT A ATT A

TAAAAATATCCCCGTGGATAAGTGGATAACCCCAAGGGAAGTTTTTTCAGGCATCGT GTGTAAGCA

GAATATATAAGTGCTGTTCCCTGGTGCTTCCTCGCTCACTCGAGCTACGGGGTCTGA CGCTCAGTG

GAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCAC CTAGATCCT

TTT AA ATT AA A A ATG A AGTTTT AA ATC A ATCT A A AGT AT AT ATG AGT A A ACTTGGTCTG AC AGTT A

CCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCAT AGTTGCCTGA

CTGCCCGTCGTGTAGATAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCT GCAATGATA

CCGCGGGACCCACGCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGA AGGGCCGA

GCGCAGAAGTGGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCG GGAAGCTAG

AGTAAGTAGTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCAT CGTGGTGTC

ACGCTCGTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGT TACATGATC

CCCCATGTTGTGAAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAG TAAGTTGGC

CGCAGTGTTATCACTCATGCTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCC ATCCGTAAGA

TGCTTTTCTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGG CGACCGAGT

TGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAA GTGCTCATC

ATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCC AGTTCGATG

TAACCCACTCGTGCACCCAACTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCT GGGTGAGCAA

AAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAA TACTCAT

ACTCTTCCTTTTTC A AT ATT ATTG AAGC ATTT ATC AGGGTT ATTGTCTC ATG AGCGG AT AC AT ATTT

GAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTG CCACCTGG

CGGCCGCCTTTCAGCAAAAAACCCCGCGAGACCCCCGAAGAGGCCCCGCGGGGTTAT GCTAGGTC

GACGGAGCTCGAATTCTAATACGACTCACTATAGGGAGACCCAAGCTGGCTTG

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OTHER EMBODIMENTS

All of the features disclosed in this specification may be combined in any

combination. Each feature disclosed in this specification may be replaced by an alternative feature serving the same, equivalent, or similar purpose. Thus, unless expressly stated otherwise, each feature disclosed is only an example of a generic series of equivalent or similar features.

From the above description, one skilled in the art can easily ascertain the essential characteristics of the present disclosure, and without departing from the spirit and scope thereof, can make various changes and modifications of the disclosure to adapt it to various usages and conditions. Thus, other embodiments are also within the claims.

EQUIVALENTS

While several inventive embodiments have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the function and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations and/or modifications is deemed to be within the scope of the inventive embodiments described herein. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the inventive teachings is/are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific inventive embodiments described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, inventive embodiments may be practiced otherwise than as specifically described and claimed. Inventive embodiments of the present disclosure are directed to each individual feature, system, article, material, kit, and/or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and/or methods, if such features, systems, articles, materials, kits, and/or methods are not mutually inconsistent, is included within the inventive scope of the present disclosure.

All definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and/or ordinary meanings of the defined terms.

All references, patents and patent applications disclosed herein are incorporated by reference with respect to the subject matter for which each is cited, which in some cases may encompass the entirety of the document. The indefinite articles“a” and“an,” as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean“at least one.”

The phrase“and/or,” as used herein in the specification and in the claims, should be understood to mean“either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with“and/or” should be construed in the same fashion, i.e.,“one or more” of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the“and/or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to“A and/or B”, when used in conjunction with open-ended language such as“comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

As used herein in the specification and in the claims,“or” should be understood to have the same meaning as“and/or” as defined above. For example, when separating items in a list,“or” or“and/or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as“only one of’ or“exactly one of,” or, when used in the claims,“consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term“or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e.“one or the other but not both”) when preceded by terms of exclusivity, such as“either,”“one of,”“only one of,” or “exactly one of.”“Consisting essentially of,” when used in the claims, shall have its ordinary meaning as used in the field of patent law.

As used herein in the specification and in the claims, the phrase“at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase“at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example,“at least one of A and B” (or, equivalently,“at least one of A or B,” or, equivalently“at least one of A and/or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one,

B (and optionally including other elements); etc.

It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited.

In the claims, as well as in the specification above, all transitional phrases such as “comprising,”“including,”“carrying,”“having,� �“containing,”“involving,”“holding,” “composed of,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases“consisting of’ and“consisting essentially of’ shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03. It should be appreciated that embodiments described in this document using an open-ended transitional phrase (e.g.,“comprising”) are also contemplated, in alternative embodiments, as“consisting of’ and“consisting essentially of’ the feature described by the open-ended transitional phrase. For example, if the disclosure describes“a composition comprising A and B”, the disclosure also contemplates the alternative embodiments“a composition consisting of A and B” and“a composition consisting essentially of A and B”.