FreshPatents.com Logo
stats FreshPatents Stats
n/a views for this patent on FreshPatents.com
Updated: January 23 2015
newTOP 200 Companies filing patents this week


Advertise Here
Promote your product, service and ideas.

    Free Services  

  • MONITOR KEYWORDS
  • Enter keywords & we'll notify you when a new patent matches your request (weekly update).

  • ORGANIZER
  • Save & organize patents so you can view them later.

  • RSS rss
  • Create custom RSS feeds. Track keywords without receiving email.

  • ARCHIVE
  • View the last few months of your Keyword emails.

  • COMPANY DIRECTORY
  • Patents sorted by company.

Follow us on Twitter
twitter icon@FreshPatents

Diagnosis and risk stratification of infections and chronic diseases of the respiratory tract and lungs by means of provasopressin, particularly copeptin or neurophysin ii

last patentdownload pdfdownload imgimage previewnext patent

20120270245 patent thumbnailZoom

Diagnosis and risk stratification of infections and chronic diseases of the respiratory tract and lungs by means of provasopressin, particularly copeptin or neurophysin ii


The invention relates to a method for diagnosing and/or stratifying the risk of infections or chronic diseases of the respiratory tract and lungs, particularly lower respiratory tract infections and chronic obstructive pulmonary disease. In said method, provasopressin (proAVP) or fragments or partial peptides thereof, especially copeptin or neurophysin II, is/are determined. The invention further relates to suitable biomarker combinations for in-vitro diagnosis.
Related Terms: Lungs Respiratory Tract Respiratory Tract Infections



Browse recent Brahms Gmbh patents - Henningsdorf, DE
USPTO Applicaton #: #20120270245 - Class: 435 792 (USPTO) - 10/25/12 - Class 435 
Inventors: Andreas Bergmann, Nils Morgenthaler, Jana Papassotiriou, Joachim Struck, Beat Müller

view organizer monitor keywords


The Patent Description & Claims data below is from USPTO Patent Application 20120270245, Diagnosis and risk stratification of infections and chronic diseases of the respiratory tract and lungs by means of provasopressin, particularly copeptin or neurophysin ii.

last patentpdficondownload pdfimage previewnext patent

US 20120270244 A1 20121025 1 30 1 19 DNA Artificial shKLF-15 sense oligonucleotide 1 gatgtacacc aagagcagc 19 2 18 DNA Artificial shKLF-15 antisense oligonucleotide 2 gctgctcttg gtgtacat 18 3 22 DNA Artificial FLF15 or BNP primer forward 3 gctgctttgg gcagaagata ga 22 4 22 DNA Artificial FLF15 or BNP primer backward 4 gccaggaggt cttcctaaaa ca 22 5 21 DNA Artificial PCR primer to assess the genotype of TbetaRI flox 5 atgagttatt agaagttgtt t 21 6 21 DNA Artificial PCR primer to assess the genotype of TbetaRI flox 6 accctctcac tcttcctgag t 21 7 21 DNA Artificial PCR primer to assess the genotype of TbetaRI flox 7 ggaactggga aaggagataa c 21 8 21 DNA Artificial Mouse BNP forward primer 8 gtttgggctg taacgcactg a 21 9 22 DNA Artificial Mouse BNP backward primer 9 gaaagagacc caggcagagt ca 22 10 24 DNA Artificial Mouse ANF forward primer 10 attgacagga ttggagccca gagt 24 11 24 DNA Artificial Mouse ANF backward primer 11 tgacacacca caagggctta ggat 24 12 20 DNA Artificial Mouse aska forward primer 12 tgagaccacc tacaacagca 20 13 20 DNA Artificial Mouse aska backward primer 13 ccagagctgt gatctccttc 20 14 21 DNA Artificial Mouse PPIA forward primer 14 caaatgctgg accaaacaca a 21 15 20 DNA Artificial Mouse PPIA backward primer 15 gccatccagc cattcagtct 20 16 21 DNA Artificial Human LIMP-2 forward primer 16 gtttgggctg taacgcactg a 21 17 22 DNA Artificial Human LIMP-2 backward primer 17 gaaagagacc caggcagagt ca 22 18 21 DNA Artificial Human GAPDH forward primer 18 acccactcct ccacctttga c 21 19 22 DNA Artificial Human LIMP-2 backward primer 19 accctgttgc tgtagccaaa tt 22 20 21 DNA Artificial Rat LIMP-2 forward primer 20 tgcgtccaaa caaggaagaa c 21 21 25 DNA Artificial Rat LIMP-2 backward primer 21 aatctcttgg cccctcttaa aataa 25 22 18 DNA Artificial Rat PGK-1 forward primer 22 cggagacacc gccacttg 18 23 25 DNA Artificial Rat PGK-1 backward primer 23 aaggcaggaa aatactaaac attgc 25 24 53 DNA Artificial Rat shLIMP-2 sense 24 ggaagaacat gagtcatttg tcaagagaaa atgactcatg ttcttccttt ttc 53 25 57 DNA Artificial Rat shLIMP-2 antisense 25 tcgagaaaaa ggaagaacat gagtcatttt ctcttgacaa atgactcatg ttcttcc 57 26 2543 DNA Homo sapiens 26 ccacgcgtcc ggcgacccgc gggccggcgg gcgatcgagc cagcgcagga cccgcggctc 60 ggcccccggc cgccgccgga ccgagagtct agccgccgcc cccagcccag cccgcccggc 120 cgcaggaccg ccggggcctg gccgccggtc cggcgtgcgc caagttcagc cgccaccggc 180 acggccaggc cagcatggtg gaccacttac ttccagtgga cgagaacttc tcgtcgccaa 240 aatgcccagt tgggtatctg ggtgataggc tggttggccg gcgggcatat cacatgctgc 300 cctcacccgt ctctgaagat gacagcgatg cctccagccc ctgctcctgt tccagtcccg 360 actctcaagc cctctgctcc tgctatggtg gaggcctggg caccgagagc caggacagca 420 tcttggactt cctattgtcc caggccacgc tgggcagtgg cgggggcagc ggcagtagca 480 ttggggccag cagtggcccc gtggcctggg ggccctggcg aagggcagcg gcccctgtga 540 agggggagca tttctgcttg cccgagtttc ctttgggtga tcctgatgac gtcccacggc 600 ccttccagcc taccctggag gagattgaag agtttctgga ggagaacatg gagcctggag 660 tcaaggaggt ccctgagggc aacagcaagg acttggatgc ctgcagccag ctctcagctg 720 ggccacacaa gagccacctc catcctgggt ccagcgggag agagcgctgt tcccctccac 780 caggtggtgc cagtgcagga ggtgcccagg gcccaggtgg gggccccacg cctgatggcc 840 ccatcccagt gttgctgcag atccagcccg tgcctgtgaa gcaggaatcg ggcacagggc 900 ctgcctcccc tgggcaagcc ccagagaatg tcaaggttgc ccagctcctg gtcaacatcc 960 aggggcagac cttcgcactc gtgccccagg tggtaccctc ctccaacttg aacctgccct 1020 ccaagtttgt gcgcattgcc cctgtgccca ttgccgccaa gcctgttgga tcgggacccc 1080 tggggcctgg ccctgccggt ctcctcatgg gccagaagtt ccccaagaac ccagccgcag 1140 aactcatcaa aatgcacaaa tgtactttcc ctggctgcag caagatgtac accaaaagca 1200 gccacctcaa ggcccacctg cgccggcaca cgggtgagaa gcccttcgcc tgcacctggc 1260 caggctgcgg ctggaggttc tcgcgctctg acgagctgtc gcggcacagg cgctcgcact 1320 caggtgtgaa gccgtaccag tgtcctgtgt gcgagaagaa gttcgcgcgg agcgaccacc 1380 tctccaagca catcaaggtg caccgcttcc cgcggagcag ccgctccgtg cgctccgtga 1440 actgaaagcg ccctgaaccc cagcctgtcc gtcaccccgg atccccaccc catccccatt 1500 tttttaagca ataatttatt tgcctcctcc agagggacat ggcaatgtta ccagcccacc 1560 ttctgaagcc tgggaggtgt gaacccaggg cccgccaacc gctgcctttc tcgggagtac 1620 ttagagcctc gaacccgcgt ccctgggggc tgggccccag gcgcacgggg ctggaggcag 1680 gccttcgtgc cttcgtgcct tcgtgccttc ccgcggtggc caggcctctg ctgcagccgc 1740 tggttgcagg cagagttttg gggacctggc ccttctccca ctgggctccc ccatcctggg 1800 ccaaggccag aactttagtg ctaggggaag atgaaatgtg cagttttgaa atgttgggtt 1860 tccagagaga gtcatgctgg aggagaagga agtaggccag aagtccaggg ctgcactgtg 1920 gtgtgagggt ggctttgtct aagatgcctg ctcagcatga tcaccagagg gtgtgggcag 1980 gtccctggag cggggggggg gggggggggg ggcggaccgg gccgctgggc cctcatgtgg 2040 gagagaggtg aaaagcgtcc cccactaggg ggctggcagt gcatgtgctt gagttaaatg 2100 tgcagggcag acagagccag aagggcctgt acccaggggc tcgtcccctc ctccggtttc 2160 ccagacaaat ccagacacca gcctttaggg tggccttggg aggagagggc caggctgtcc 2220 tgggtgtgag agaactagat agagcctccc aaccctgatt tagaaatgca ttccttattt 2280 tgtctagaaa ttaataaatg aactagcttg ttttgacagg tttatttcac atcctatgaa 2340 tgtatgtaaa taaactgtac ataggtccat ccacataaaa tatcttttaa taacatatca 2400 acatttgtgt aaatttgaaa tttaaaaaaa tctatgaagc tggtgtacat atgttacaat 2460 tacgtatatt ttctttggtc cttcataaaa atatatttac tttgccaata aaaagaaaaa 2520 gaactcacaa aaaaaaaaaa aaa 2543 27 416 PRT Homo sapiens 27 Met Val Asp His Leu Leu Pro Val Asp Glu Asn Phe Ser Ser Pro Lys 1 5 10 15 Cys Pro Val Gly Tyr Leu Gly Asp Arg Leu Val Gly Arg Arg Ala Tyr 20 25 30 His Met Leu Pro Ser Pro Val Ser Glu Asp Asp Ser Asp Ala Ser Ser 35 40 45 Pro Cys Ser Cys Ser Ser Pro Asp Ser Gln Ala Leu Cys Ser Cys Tyr 50 55 60 Gly Gly Gly Leu Gly Thr Glu Ser Gln Asp Ser Ile Leu Asp Phe Leu 65 70 75 80 Leu Ser Gln Ala Thr Leu Gly Ser Gly Gly Gly Ser Gly Ser Ser Ile 85 90 95 Gly Ala Ser Ser Gly Pro Val Ala Trp Gly Pro Trp Arg Arg Ala Ala 100 105 110 Ala Pro Val Lys Gly Glu His Phe Cys Leu Pro Glu Phe Pro Leu Gly 115 120 125 Asp Pro Asp Asp Val Pro Arg Pro Phe Gln Pro Thr Leu Glu Glu Ile 130 135 140 Glu Glu Phe Leu Glu Glu Asn Met Glu Pro Gly Val Lys Glu Val Pro 145 150 155 160 Glu Gly Asn Ser Lys Asp Leu Asp Ala Cys Ser Gln Leu Ser Ala Gly 165 170 175 Pro His Lys Ser His Leu His Pro Gly Ser Ser Gly Arg Glu Arg Cys 180 185 190 Ser Pro Pro Pro Gly Gly Ala Ser Ala Gly Gly Ala Gln Gly Pro Gly 195 200 205 Gly Gly Pro Thr Pro Asp Gly Pro Ile Pro Val Leu Leu Gln Ile Gln 210 215 220 Pro Val Pro Val Lys Gln Glu Ser Gly Thr Gly Pro Ala Ser Pro Gly 225 230 235 240 Gln Ala Pro Glu Asn Val Lys Val Ala Gln Leu Leu Val Asn Ile Gln 245 250 255 Gly Gln Thr Phe Ala Leu Val Pro Gln Val Val Pro Ser Ser Asn Leu 260 265 270 Asn Leu Pro Ser Lys Phe Val Arg Ile Ala Pro Val Pro Ile Ala Ala 275 280 285 Lys Pro Val Gly Ser Gly Pro Leu Gly Pro Gly Pro Ala Gly Leu Leu 290 295 300 Met Gly Gln Lys Phe Pro Lys Asn Pro Ala Ala Glu Leu Ile Lys Met 305 310 315 320 His Lys Cys Thr Phe Pro Gly Cys Ser Lys Met Tyr Thr Lys Ser Ser 325 330 335 His Leu Lys Ala His Leu Arg Arg His Thr Gly Glu Lys Pro Phe Ala 340 345 350 Cys Thr Trp Pro Gly Cys Gly Trp Arg Phe Ser Arg Ser Asp Glu Leu 355 360 365 Ser Arg His Arg Arg Ser His Ser Gly Val Lys Pro Tyr Gln Cys Pro 370 375 380 Val Cys Glu Lys Lys Phe Ala Arg Ser Asp His Leu Ser Lys His Ile 385 390 395 400 Lys Val His Arg Phe Pro Arg Ser Ser Arg Ser Val Arg Ser Val Asn 405 410 415 28 55142 DNA Homo sapiens 28 cctcgcgggg ttgcggcgag cccggcccgc gaacgtcacg tccctgcgcg ctccctgcac 60 tctcccgagc tgcgctaggc gggcgccacg gctgcccggc gaaggaaacc gaaaccgagt 120 ccgggcccgt ccctccgcgg ccccatccgc ccggtgcacc cggggccgcg ctcgccaggc 180 cgcggagccc agagctgcgc gcacgaaccg tgcgccggga gggcgtgggc gtggcgccga 240 agggtcccgg gtcttcgacg cctctgcggc ggctcctccc tccttgcagt tggatccctg 300 gcgggtgcgg cccggcccgg cccgtgagcg gcgcacagaa tgggccgatg ctgcttctac 360 acggcgggga cgttgtccct gctcctgctg gtgaccagcg tcacgctgct ggtggcccgg 420 gtcttccaga aggctgtaga ccagagtatc gagaaggtga ggcggggcgg gctgtgtgtg 480 tgttgtggag tcgtccagct caccctccca tccctgctgc tacatcttgt atgggaaaga 540 ccagcactca ggcagaccct ccgcgctaga gctcttcttg cgtccctgtc ttccagggct 600 tggtaggcga gggttaaaga aggatgagga aggatggagc cgactctgtt ccctttacag 660 tgataagtaa ggctatggat cctgactttt aaaaaggcct tcggttgtgt tctgtcgttt 720 gcatctctcc ccactccttc cgtctacacc ccaatctcag gtgggcccaa acttgtttcc 780 ttcccacttc atgaagaaac agaactgaat gaaagacacc gcagaagagg caggttatgt 840 tgtctgcttg ctgtagcctt tgaagtggtg tgcgcctggg gatgagacgt gggtgtgcgg 900 tctattgtgt tcttgccctc ttgggctggg caggggcagt tggtagctgg gccagtcctt 960 taggctgggt gacaattcat ccatcagtct ttgctgaacg ctgacttagt ggctttgtat 1020 cttgtaccaa cagtctgtgt tgctttgtct caccatgaat tcttgttttt ctcaaacggc 1080 cataattttc aggcacagat gcatttagat accctacaag aatctgaact tgtctcttcc 1140 tctagatgat tgggctggag agccagtcct ttaagaagac ttcatctttt gatttcactg 1200 gtcatttcat ctgccctttc ccccacatcc accaagctgt gtcaaaagag gaacaaaaga 1260 gaattactgg gatcattttt tccttaaaaa agaaaaataa tcactggagc agcagccttt 1320 cttgttagca tccataactg cacgcttcat ttctcccact ggtctgcact tgctgcggcc 1380 agataaaaaa gcccaggcct agtctacttt gaatcactgc actctccagt cagtaaagct 1440 attttattcc aggtggcaat ggatatcttc ctttaactga gtttccaaaa gtaattaagt 1500 gagtacctga aatctggcag ttaaaggcag tttttcaaaa agcaccatgg caaagcataa 1560 tgtaattttt aaagttcaca ttgccaaggg aagacaaggc ccactgtctg agcgtctcga 1620 gggtcagttt cctttgagca atcatgttca aggaaaaaag aaactgaatc ctttctccac 1680 tcctgtccat gtccaaatcc atggtgagct gtgtttgagg atgtaaactc ttgctttggg 1740 tgactagagt aaagcaatcc aattatagta aatatgtgag ttttcttata tggccttgaa 1800 aggctgtttc aaggagccct ataggatgag tgatcttccc cgtggttccc atatagccag 1860 cccttagatt ctctgtgtgt ctccatttct ctgggtgagg gggtggctgt aaggcaactt 1920 ggctggggcc tgagtttgtg ttgatatttc caagtgtttt tctccatgag gaatggactc 1980 tgttctgata agtaatagta cagggaagtg gactttcaga gctgctcaat cccagctaag 2040 gaggactgca cggtgtattg tatgaaacta aaggacaggg ctagtttcag tgggcaggtg 2100 tggaaatact gttgtcatta gaggtaagtc acacatcgct attctgcttt ttcctggatt 2160 acctgtaggg tggtaggtag catgggacag tgggaaagat tgaggatgtt acactcctgg 2220 gcatgaaacc tagcttccac tatgtcccag ctcggtgacc gtgggctgtt taatcttact 2280 tgattcatgt tttccccatc tgtaaatagg gataataagg actaacgatc acatctgctt 2340 tgtcaaataa ttcttataac cttaaggtgt gatctttctg ggatatagtt agtgcttaat 2400 aggtgatagc aactttattt ttattagaag ccacacaaag aaaatacgtg agatttggag 2460 tcagattcca tatgttcaaa tcctatcctt gccagtataa gctttatgac ttacgtcaaa 2520 taacttactt ggtcctcaat ttcattgctt gtaaaactgg ggatatgagc tgttagctaa 2580 cttgggcaca gtgatgcatt taccatgaaa ctcgcaaagt taagctttgg gtctctcact 2640 tgcacagacc cttgcgaagc cctgtacctc attctatatc ccaaattttc ttttttctta 2700 agaaggaccc ttcaaattgt ataagcttca ggacccacaa aacctggatt tgtctctgca 2760 tgtgtattat tgtaggacca agtataaagc acttagcata gtatcaggca cagaataggt 2820 aatcaatatg tggcagtcat ctttattgcc actagtatta ctatgggaga attcattcat 2880 aacttgattc taatgtagtt ataatataat ctactctgat atttccagtt ctttgttttt 2940 tcatttgaag attgtctatg ccccgacttg tctatgtcaa aaagggaaga gggaaaaggg 3000 atgaaattca aatgagtagg tgtgggaagc ttagtaagag aattcctatc caaaaagttg 3060 tctcaaatga taattgtcct tgaaccctgc agtgaccaga ggtaactgaa gagagacttt 3120 taattttggc cagtgaatat cgtggaagga accaagacaa ttttgtttca tttttggcct 3180 cagtggtgac tgcctcgtat tgggcaaggc ctgtaattgt ttctgcttca attttctcat 3240 ttgcaagaga ggcataatag tacttctctt tttcccacac cctcttccta ggggatattg 3300 tgagcattaa taaggcattt ccttacaagc gtttgggcct tcatgaagag agagctttgc 3360 agagacccag cagttccttt tcctccctta ggcctggaaa ggcaggagtt tacgttacat 3420 ttcatctggt atcccagtga actgccttga cacctagcac agtgcctgag atacatatta 3480 aatgcctctt cactcgcctg tgatcatttt aatagaaaga agagtgtcct gagaatcagc 3540 agaactgaat caaacatttt ttttctgtcc ctaaggattt cttggactaa gctgaacaag 3600 cacagtggca agttatttaa tccctcaaat cctaaggatc ctcattttga aaataggaac 3660 aataaggata agaatactta actcagagtt gtcacaagaa tgaaataata tgatatctat 3720 aaagcaccca gcacaatgcc tcgcacaatg cctgaacgtt aacagttgtt atgtctttag 3780 ctatatttgt catctgtgaa ttgaaactta ttatacaagc tatggttcct cttagctcca 3840 aacttctgag atcccatgac ctttaagagc agctatgcag ttcagaatat taagtttgcg 3900 ctcctaatct ctgcagacgt gctggcaggt tgactgtctc ccagtaatag ggatgcagaa 3960 ctggccacag tcagggctgg ccaacaaggg atgggatggc aagggaacca gtgggagact 4020 gtttacacct ttgacttcct cttcacaggt caaggcagga ctgtagcatt aggtctcaga 4080 gatgcaatga acaggacaaa tacacttccc cttcatctgg acctgaggct ctgggcaagt 4140 cagtaccagc tggtttcttt tgggagccat agaaactctg gagctgttct accgattcct 4200 caagaagtaa aatataggcc aggcgtggtg gctcacgcct gttatcctaa cactttggga 4260 ggctgaatcg ggtggatcac aaggtcggga gttcgagacc agcctggcca atatggtgaa 4320 accctgtctc tactaaaaat acagaaatta gctaggcatg gtggcaggtg cctgtagtcc 4380 cagctactcg ggaggctgag gcaggagaat cgcttgaatc cgggaggcgg aggttgcagt 4440 gagccaagat ggctcccttg aactccagcc tgggcgacag agcaagactc tgtctcaaaa 4500 aaaataaaaa taaaaataaa aaaagaagta aaatgtaatc actgataacc agattgcttt 4560 gattggtgac tatgggatct tgttttttaa agtcaaatca gcaaaacatc tttattgatg 4620 tgtatgtaaa ggcattcagc tatatatcat tttaaaaggc tccttcttgc atatctacct 4680 catctcctga gttgcctcta ttcaaagaag acttatctta gtctgagatt tttcttgatc 4740 agaaaaaaac ctgtaaagat atcttaaatc tgttatctta cggtcaagga aattgaggct 4800 cttggaatag aagtgactta tctaaagtca aatggagagg gaaggagaga gcgtgccagc 4860 tagccttctg atcctgaacc cacttttccc atctcaagga tgaccataca tcccatttgc 4920 ctggaatagt cctacatggt ttctgtgtac ctgttgtgct ggtgtaatca ctaacacccc 4980 ctttcctcca aaagatttct gctttggaca ataaattcta tggccatccc tcacctctca 5040 tgctacattg tccttacaga ccacaatgta tcccgcttct tggctctctt aaggagttga 5100 ggcctactca aactagctct ggcaagagag gattcttttt tttgtttctg taaatctgga 5160 aggggaagct catagaaatc aaagggcaag aaccacggca cagtaaggcc tcctgagagg 5220 acaaccgaaa gtggaaagtc agcaggaagc aggcacactc tgcctcccac tttttcctct 5280 gctttctcca ccaacaggct tcctctgttt actcagcctg gctctgtact catccgggct 5340 tgctcagccc cgcctcagtg tgactttcca gctgttgacc tctcatagac atgcttcatc 5400 tcctagtttc tcttttccaa gtttataacg gagcaatgtg attggctcag cacaggaaga 5460 aactatagca ctgtaaacgg aggcagtgtc gttaatttcc ttgcaagatt ctctaactcc 5520 taagcaaaat tatccaaatt ctttcctggc ttttagaaac acgatcttgt gatatcaaaa 5580 tcatattaag tttattttag tgtcttacta attcatgttg actatgagtg cattccttat 5640 taatgattaa gacaatatag taggctaaca gttgtcagca tagcccctag actctaggag 5700 atgcatctaa atcacttaca aagatttaga aaataccaga ccccatccca gacttgctga 5760 atcagactca ttaggaacag aactcaggtt aaagtgctta tcataaaatc cattactgga 5820 ggcaggttgc tgtgggatcg taatctgcaa ttttgggaat atgcattttt aaaaaaggtg 5880 tttatatttg tatagtgatt attttagacc atgtcttcat tccttaagat ggtaattctg 5940 actgaggaga ttactactta taattactat taatctgcaa gtttacatta aaggaaatat 6000 tatttggtga ggaggggaag attcctgcct gtggaaacta ctttgcttta ttgttaaata 6060 aatccaagat ttcattctgt caggccacag cagaggggcc atctgttctg ccagacattt 6120 gcttatttcc caggaagaat caggaggtgg aattataagc tcattgatga aaacatagga 6180 tgttggccaa gttactagac attcctggcc atatcatcaa gatatgcact atctatacac 6240 tatacactaa ggaagggacc atttttaatc caagctggta actggaaaaa acaaccaagg 6300 aaaaataaag accactttag gtgtttgctt tctatatcta aatgcacttt tgggtacatg 6360 ctttggcagt cattctttca tttgacaaat atttactgag tgtgtaccat ttgcaaggca 6420 gtgtgctaag agctatggat ataacactaa acaagaggca gtctctaccc ttgcagattt 6480 tataatccaa tttaaactcc tgggcccctc atattcttaa aaattattga ggaccccaaa 6540 gaacttatgt ttccatacct attgatagtt acaatattag aaattgaaac tgatatgtat 6600 ttttgagaaa tgtttaaaac agaagactac acaagcacat attccaatat gacatcatta 6660 tatatcacgt aacctctgga agactccact ctacactcag agaaataata gaattaaaaa 6720 cgcaaatgat accttagtat taaaatagtt ttgaccttgt gggcgcctcc taagaaggtc 6780 ttcgggctcc ccaggggtcc tgagatcaca ctttgagaac tgttgatcta gttttcattt 6840 aattattttt ttagaatatt tttaaaaata cataatatcc ctgttttata ttcctgtaag 6900 gccagtttgg aagctatctt gttaatgttt tcaaacaacc aggattttgc ttggtgtgtc 6960 tttgatttac tgtgtccttt tggctttcct gtgagtccag tgttaaaaat aggagtttgg 7020 gccatcagta attccagttc cacaatctct tgtctttccc cgagtgctga tcaaagtaga 7080 caagagcatt catatctcca taattgaatt actcagtaat tcccttctgg cctcagccct 7140 gcggggattt tcaacccata tgacgtaatt tggtatttta atctagtatg aaagctctct 7200 ttgaaggtag atgtcctgtc gtatttagtt ttgtgtcttt tcttactgcc aaatgcaatg 7260 tcttattcaa aatagatggt cagtaagtgt tacttggatg aatagagaaa ataatttctt 7320 tggaaatgat tttgtttgca ttttgttgtt tagtctcaca ttttgcctca ctctgtaggc 7380 cagtggtcac atgtttgtct catgaatgat ttataccttt aaaatctgga aacttcacgt 7440 attggtccag atttccagct tctcttgaaa catgtggatg ttctttggta ctcgtcatac 7500 caagttctgt gtggtagctg tctcggcaga aaagaggctg acccttagaa gagacctgcc 7560 ttccctgttt cccactgtct tagtccattc aggctgctgt cacaaaatag catagactgg 7620 gtggcttata aacaacagaa atttatttct tacagttctg gaggctagga agtccaagat 7680 caaggccccg gcagatttgg ggtatggtga gggtccactg cctcatagat tatggtcttc 7740 tcactctaac ctcacatggc aaatgagctc tctggggtac cttttatgag aactaatccc 7800 attcgagagg gttctacgct cgtgacctaa tcacctccaa aggccccacc tcctaatctc 7860 accaccttgg gggtaaggat atcaacaaag gagttttgag gggacataaa cattcagacc 7920 acagcaccca ccgtcctttg cgcccttatt ggctcccaag gcccagtgaa ggtatccgtt 7980 gttgtgcatg tgctgttgtg tttcttagag tagagaaatg tttctctata tctgacactc 8040 cttaccaaaa gaaggaaaat gaaagatagc ttgagaggat catgtgttta acagaaatgg 8100 gggagggcat gtttctctgt agaaatgaat attgctgctg gggtttgaca tgcaaacaaa 8160 tgtacaaacc catggcctgt gtcactcatt tgccctagcc atctggcccc ttcagcatct 8220 gaattttaca cactttccag agacagtgtg aggcagagtg ccattgttac actaatgtaa 8280 tcactcatca caagtcccat tttttaaaat tcatttttta attgacaagt caaaattgta 8340 catatttagg gcatgcaaca tgatgttttg agagagatat acatatagat atacatagtg 8400 aaatggctaa atcaagctgt ttaacataca ccttacctca attacttatc tttgttttgt 8460 ggtaagaaca caaaatctaa tctcagcatt tttcaaatat acaatatttt ggggttttat 8520 tttattttat ttttgttttt gtttttgttt ttgttttgag atagggcttc tctctgtcac 8580 ccaggctgga gtacagtgcc actaccatgg ctcactgcag ccttgacctc ctgggttcaa 8640 gccatcctcc tgccttaaac tctaaagttg ctggaactac aggtgtgcac catgccaggc 8700 taatttttaa atattttttt gtagagatgg ggtcttgctg tgttgcccag gctggtctca 8760 aattcctgag cttaagcaat cctcccacct ttgcctccta aagtgctggg attacaggcg 8820 tgagccactg tgcctggccc aatatattgt tatccactgt gatcaccatg atgtacatta 8880 gatctcttga atttgtttat atcaaactga aattttgtgt cctttgacta acatctcacc 8940 agtcctccca gcgcccacaa ttcccatttt aaggatattt tcttttaaca ctgtacttct 9000 gataatcaac agtagtggaa gaggagacat agaaataggt aggtaatgaa aatattactt 9060 atttcaattt tgagagatat aatcacaacc aaacaggttg caaaataatg agactggctg 9120 tgcaagttac acacagaatg tgggccttgt ttccgtggcc ttatttctta tttattcaca 9180 tctgaaactc ctctttctca cccgcctccc cactccccat atatgtatat atatattccc 9240 ctcccgctcc caattttcac ctggttctat gtttaagttt ctatcggtag ctgctttttt 9300 tccctttagg tcatcagttc tcaaacttgg ctgtacattt gtaatcacct agaaactttc 9360 aaaaataagt tagtgggtat tttgtagcag gaggtttttt gggattgtca ttccaccata 9420 ttgtcctgta tgtaatttat aaacaaagta cagttcaccc atgagctaca tttgaatctg 9480 aactatcaga gctcattagt taaaattatg acagttgcaa aatgaaaatg agttaagcaa 9540 cagtgacata aataaatgaa tgccaataca tttttactga gttaaaataa ggtcagggaa 9600 taagagtaga atgttaatgg cagtttcttt cttttatgta aacagtggaa attacttaaa 9660 ttactgcatg agtctgggtt gggtttgctt cgtttcaggg agcaatttta aaaaacaaag 9720 caaatcaatt ggtgttttgc catttgatga gttttattaa tctggagtcc agtatacaat 9780 taggccaata taccatccat acacaattag ggcaagttct ccaagttggt ctgcattatc 9840 tctggatgaa tttagactgt gcagatggca acatggatgc ttaagttgtg tttaattatg 9900 aagtagcact ttactgacct taaagaacaa ccagtagtgc tctcgaatcc cgaaactttc 9960 cttaaaggta ttactgattc ccgtgaaagc ctaatggatt ccctgagtgc ttatttttat 10020 cacttggaag tggcttacat caggacagct ggtttcacca ctctcatggt gttgccttcc 10080 caaaagattg ctgttaggct gacttgggtt gtggctgtat taagtcatgt cagtgttcag 10140 cagtcaagct aatccagcct gcatctgttc cttcatctgc aggtcaggtg tcagcctggc 10200 cagcgactcc atgttcacta cacacagctc agagaggttg ttctcagttc tgtctctgac 10260 cagccttctg tgtacccaaa tggaagctta tgctggttga agattctttt acttttgttt 10320 taaaacagtc tcacttcata catggtaaaa actgttatgc ttctccagta attcaagaaa 10380 tgcaagttca aacaagaaga tgctattttg ccactactga ggaagcaaag atttctgaaa 10440 accttaaaca ccaatattgg gatggatatg ctgaaatggt tgctcataca ctgctttctg 10500 gagcaacttg ttgatattta aaggctgatg agttcatgaa aactttttgt ctctagaccc 10560 aataatccca atctaggagt ctattctaag aaattattca ctgatttggg ccaggtgtgg 10620 tgcctcatgc ctgtagtccc agcactttgg gaggccgagg taggtggatc acttgaggcc 10680 aggagttaga gaccagcctg gcccacatgg ttaaacccca tctctactaa aaatacaaaa 10740 agtagctggg tgtagtggtg tgcacctgta atcccagcta ctccagtggc tgaggcatga 10800 cagtcaaaag ttgcagtgag ccaagattgc accactgcat tccagcctga gtgacaaaag 10860 caagactctg tctcaaaaaa agaaaacaaa attattcact aatttggaca aatatattca 10920 agaacattta cttcagcatg aaagcaacac aaatgtccta tagtaaaaga atgattaaat 10980 aaactgattt agtatatttt tttaaatata ctaatacagt ggattagtat acagacatta 11040 aaataacagt ttcaaaacct atttaataac aaggataatc gtttataaaa gatgagtcaa 11100 aaaatgatac aatacatatg atctcaattt tgtttaaaat acacatatat atgactagac 11160 cagagggaaa taaacccata tgttaacagc gatagtgtgg attacagggg atttaaattt 11220 tgttcctttt actttcttca ttgtccaaat tttctgtgac aaatataatg gaatgggtag 11280 ggaatggatg gagtagcatt tacctgattt aaagtaacaa caggctgggc acggtggctc 11340 acacctgtaa tctcaacact ttgggaggct gaggtgggca gatcacctga gatcaggagt 11400 tcaagatcag cctgactaac atggtgaagc cctttctcta ctaaaaatac aaaattagcc 11460 aggtgtggtc atgtgtgcct gtaatcccag ctactcgaga ggctgaggca ggagaatcgc 11520 ttgaacccgg gaggcggagg ttgtggtgag ccgagtcatg ccactgcact ccagcctggg 11580 caacagaatg agactccctc tcaaaaaata aataagtaac tgaataaata aaaaataaag 11640 taacaacaat cagtagcatc atttgtgaat agaaattgga ggcaacacat gactttttct 11700 gcacatttgt agtaatgtta tctgctactt taaacatctc ttctaatatg aatatagaaa 11760 tttctgtaga ttgataattt atcataatat ctaggtattt ttcccttaga taaatgtgat 11820 gttttattgc ttacaagtct agtttgttcc ttgttatatc aaggagtttt tagaattcac 11880 caataaaatg agaaggtagg agatcttgtc taccattata tctccaatac ctagaacagt 11940 ggcttagcac aaaggaattg ctaagttaat atttgtggaa agaatgaaag agtttcatca 12000 gttttaaggt tgtgaaaatc ctatgctata cttgctatga aaaaggatgt tataaaaaat 12060 tcattaaaac caaaattgct aaagacagat ctaacagact tagaactaat gtttgtgtgc 12120 ctttggcata ttaattatgc ataaaaatag accctgctaa ttccaaacta gtcttaacca 12180 tttatgaaag gaggccaaaa tgtctccttg aaaaataata tttgcagcta agaaagttac 12240 tgtctcttct tgattctgca gtactgaaat tcagactttt tatttattca gatcaccttt 12300 cttacatatt atttagaata tgcggcattt tgccacattg aagattttac caagaagaac 12360 tgggtaaaca gcagaagatg aatgcctggc acagcgttgt gctctacgct gcggtatcat 12420 ctgtttcttc attaattatt tattgtgtcc cttctgtgcc agaaaccatg ttatgtgctg 12480 gggatccatg aaaaagatac agttcttagt atcagaccca atctgacact aaagactaat 12540 gaacacattt tccttataaa acttgtgaag tttcatgaaa gcagagagaa aacacatagt 12600 tcagaggggc cttctgagag atggcacttc tgaattgagc cctgaagccc aagtagaagt 12660 gaaccaggtg ataagggccc tgcagagact tctgggtgaa gggcggtgag tgactcaggc 12720 caaggcactg gctgagaact tgtgtggtgg gtgctaggta acagtagatg gttgcgtgtt 12780 actggtgcat aaagtgccta ccaggaaaag acagcgacag gtgacgcagt tgcatcagat 12840 cacaacaggt caaggactgt ggactttatc ctttgagcag gggtggagta tctgttccct 12900 taggcacttt tgacaggctt ctctgaagcc tgagatggat gaagcatttg aaaggaaaaa 12960 ggctggagag agggagacca gttaggagcc tacatacagt attgtcacag tccaagccaa 13020 tgatgaaatg tgccttgggg tagaaatggg gaagaggagg aggtgaaatc agcaggactt 13080 agtgatcaac taggggagaa aatcatgagt ccattttggt catgttgtct tggagcagcc 13140 tgtgagatgt ttagatgggg gaattttatc acagatccat gctactggaa ggatctaaat 13200 aatttcaggc ataagctgtt tgttaggctg aattactgag tcttgcacat aatttttcac 13260 tccctgttac atgcatgttg gttttgtgtc cttagctaaa tttcttctta cagacagggc 13320 ctatgcctgt ttgcagggca tagtccgggc acatagaaag ctctcagtag gtacatattg 13380 ggtgattaac tgaaaagtat gttttttagt ccaattatta atttagctgt tgacactgtg 13440 aattcaccat agaacttgat aattttccag tattttgttt tagtggtagt gccacagtat 13500 tgtgcgtgga aaaattcatt atgttcgtct tggttaaaac taataagcaa cagttatatt 13560 gtgactccac agtgccactc ttaatatcca gagtcacact gtaaaactga tttaaggcct 13620 tatgttgctt tttcatttag tgtaactaag aagactcagc tgattacaag gtttgtctgg 13680 tggctgtcat caccacagca gaaccctcgg tgaggaagat cagttgttcc caagccatgg 13740 ctttctgttc agactggcaa agggcgcctt tgagggggac actagctcgt tgtatctggc 13800 ggaatgaata acttcctgtg ccagacagtc cgcggtcttg aggctgaggt tattatttgt 13860 tagtttctca ggccttcctt tgccgagcaa gctcctggga gtgcacactt gaatgccctg 13920 aggatcagaa atagaagggg cagaaattaa aagtttaagt caaaacagag ccctctctgg 13980 gccatcttgt ggcaggaggt tgaggtgctt tctttggacc cattagcata ctggggctgc 14040 gcggctgcct ggaaactcta gagttgaact ctcccttttt cggttcctca cctgtgggct 14100 ccttactagg agctgacagt gacctcacgc agctgcccta gtttcctttc ctccagatgg 14160 cacgggtaac actcgaggaa accctgagag ttcagagtcc aacttatggc ttctccatag 14220 tttcactgtc cctctgggct agagttgcca aataaaataa aatacaggac aaccagttaa 14280 atttgaattt cagataacaa ataacatttt agtatgagtc tgtctcgtgt gatatttcgg 14340 ttcagtccga tgtatcagtt gttaatgtcc tgccatattt atctctctga tgcacttttt 14400 cttgaattat ttgaagtaag ttgtagatat cacacacttt gttcctaaat ccttcagcat 14460 gcatctccta tgaataaaaa catttttgat gtagcccatg caatatttgg gacataatta 14520 tattataaaa ttatttgttg tttatctgaa atacaaattt aactgggtat cccaggtttt 14580 atttgctaaa tctggcaact ctaccctcag ggtgccatgg ggtggcagct gctggatggg 14640 tgagtaaatc tgcactcctg gacttggtca gatttgattt catttactgg ctttgtgact 14700 tgggacagcc agtgccacca tttctttgtc tgcaaaatgg ggatttttat tttgtagtgt 14760 cagtgtaaaa ctcagagata aggtacatta taaagcccct agcatagcac ctgactttag 14820 cagactcaca gtagattgca gctggcgtgg cagtaatggt aactgaatag taactgccat 14880 tctctgagct gaaagtgaga aaataaaaat aaagacacac tgttttagaa atgttagcag 14940 ctgtatttac aacttccctc tgttctctca ttccccatct ctcttcctac ttagtgcatt 15000 cgcatgagca cacacacaca cacacacaca cacacacaca ctcactcact ctccagcacg 15060 tgatctactc tgggattgac agagggtttc ctgacaaaca tccaacttgt aaggtggagg 15120 aaaagagaca tatgaaagca gcaggaaaag ccaccactct tgagggcaag atttgaaggg 15180 agtaaaaggg gctatgagga tttgtctgag tgctggtgac tcaactaaga agtggccagg 15240 cagagaaggg ctgtgggggt ggagggagac agaggagaag ccccagctgt aacatggtct 15300 gggttggtta tgactctggc atgctgccaa ggacagtttt tattgttctt gtttttcatt 15360 tgctttgttt cattaagaag tcaaatgtac taaatgttta tttctatcct gaaagttgga 15420 ggaacaagtt caagtcacac tgtttacgca tgtcagaaca gccaggttta cccttctttc 15480 tggtaacccc ttctttctgg aaacccttcc acttgtcttt ggatttatgg ttgcctaaaa 15540 gctggatgcc agcccagcaa gataaaccag ggaggttagc catctgttca tttatgtttg 15600 ctgattcttt cagggttcct aattctgagg tgattttctt cacatgaaca aataaatgag 15660 atctcaagtc ctttctcact ggaaacttca cacactatga tgcttgtcag gaaaaattag 15720 gcaggaatac agagtgctca ctcaactgtc ctgacagtaa taggaagaga agtgcggtgg 15780 agtcgagagt gggggcggct gctcctgggc ctttgcagca gagcagaccg cagctgaggc 15840 agcatcaggc tcgcctttgt tttgctagaa cagaggaaag ccaagatgaa gtgagttctc 15900 tttgtgtcca ttccttctcc ttgccttagg gtctatccat aacatgctac agaatctgag 15960 tttcttagat tttcacttaa aaaaaaagat aagggaacat ttttttttct gcttacagaa 16020 gtaatttatt tctggtgtaa aaatccaaac aaaagcaaca gtgagtggaa gactcctcct 16080 aatccggacc tgaattataa ctgatacaaa ttctcgacac tcaaagttca cattttggtt 16140 tgtttatttg cagtctgtgc ttttatatta tttttgtatt tcagccgttt ttacagtaaa 16200 aatacaaggc ttttctccat taacagatag aggactgttg ggaataccag gtgttaggtt 16260 tctgttaacc tcaggcgctg tatttatcag gcctctactg ccacggtgag taacaagtaa 16320 ctccccagtc tcgttgctta taacaataat atgtgggtgt gcagccagct cagctggctc 16380 agtggaacga ggctggactc caggcttctg gtccgcttta ggactagtct acacatctcc 16440 gttttagaac ctaggctgaa ggatcagcag ctacctgtgg cctgctcttc tcttttccaa 16500 gggtggcaac ttcaaggtgg cagatagaaa cttgccatgc atcttaaggc cttagctcca 16560 aattgataca ttgccattcc acccacatcc tgttggtcaa atctagtcac ttggcctagc 16620 ctgaagtcag tgaggcaggg agaatacttc acccttaggg gagtcatggt gtattaattt 16680 gctagggctt cccgaatgaa tacaacagac tgggtggctt aagcaacaga aatttgtctc 16740 atagttctgg atgctagaag tctgagatca aggtattggc agagttggtt tcttctgagg 16800 cctgtcttct tggcttgtag agggctgtca gttctgcgtg ttttcacgtg gccttccctc 16860 tgtgcttgtc tgtgtcccag tttcctcctc cagttaggac accggtccta ttagcagggc 16920 ctaccctcat gacctcattt aaccttcatc agctctttaa agaccccgac tccaaataca 16980 ggcacattgt gaggtattgg gggttaggac ttcagcttag gaatttagag tatggggggc 17040 attattcatc ctgtaacaca gaacaggggt ggaaagtgca ggagggattg tgtgcagagt 17100 gcagtctcca ttgtcagcta acctcagtga ggctaggcct cctggttttt gaaacgggga 17160 taggcagttc cattttaggg tttttgggga tccaataaga aaatacattt aaagcccctg 17220 gtggtggagg cggtagggat ggatgtggtt tgacttgaaa aaggaccaaa actggccttc 17280 ttgggccctt ccccttgtta ttctctcatc tgggcaaact gggagtgtat ggtgcttttc 17340 agaattgctt aacttctaca gaagatacac catccatgga atcttcaaaa ataacaaagc 17400 cagcaggccc tttaggcact caatctgtgc cctaggtttt ggaaacacta tgcttcatgc 17460 ttctgcccaa gtgctgtctt tagtaccctt cctttacaat tattaattaa ttaactagtt 17520 aatttatttt gagacagagt cttgctctgt aacccaggct ggagtgcagt ggcacgatct 17580 tggctcactg caacctccac ctcccaggtt caagcaagtc tactgcctca gcctcccgac 17640 tagccaggat tacaggcacg caccaccaca cctggctgat ttttgtattt ttagtagaga 17700 cggggtttca ccatgttgac caagcacgaa ctcttgacct caagtgatct gcccgccttg 17760 gcctcccaga gtgttgggcc actgggcccg gcccctttac aaatatttat cgaaggcctt 17820 ctctgactta ttagaactgt gggctctatt ggtgtaagat atggccctgt tctcaggaga 17880 ctgcagttga atgcctgtga aatgattaaa atagtgatct aggaggtcag aatagggggc 17940 gtcccttcct ctgcttcttg ggtttaaagc caactattgc cttacatttt tgtaaatctc 18000 cttttggttt tttcctagaa aattgtgtta aggaatggta ctgaggcatt tgactcctgg 18060 gagaagcccc ctctgcctgt gtatactcag ttctatttct tcaatgtcac caatccagag 18120 gagatcctca gaggggagac ccctcgggtg gaagaagtgg ggccatacac ctacaggtaa 18180 gtcttgacca cctcctgtct tgaaagaaat acagagtgac cccaatatgg cctgagtcct 18240 tgcctcttcc caggagcaag gctccagggc tgtgtgggag cacactttct gatttcattg 18300 tctgaaacgc tgctgatgtt ttgtatgtgt gtgtgaaacc tcagcagaga atggctttgt 18360 agactgggcc aagtctcagc gtgttgtgtt ttgaagtgca gcggtttcct cctgagttgg 18420 cagactgtga ttattaaacc atgaagggtt actccttacc ctgacccttt taaggttgcc 18480 ccttgatatt cttattttat tttattttat ttttttaaga gacaaggtct ggctttgttg 18540 cccaggctgg agtgcagtag agcagtcata gctcactgcc acctccaact cctgggctca 18600 agtgatcctc ctgcctcaac ctccctagta gctgggattg caagtgttca ccaccacacc 18660 cagataattt tttttgtaga gatgaggtct tgctatattg cccaggctgg tcttgaactc 18720 ctgggctcag gtgattctcc cgcctcagcc tcccacagtg ttgggattac aggcgtgagc 18780 accaccatgc ctggctactg cttgatattc ttaagtgact tttagggcct ccctccattt 18840 ccattcccca cataactagt tttaaagcag ttccagaatt tacttttgtc tgagacagat 18900 ctttctgttt cttacccgct ccttttctcc acctatcctg cgtataagca ataagcaagt 18960 agcagaggct gttagagtct ttgctggtga ccaccaattc caaacactgg ggaatcagga 19020 tccctttaat catttttaaa cgattagtag agggagacgc ttgaatcaga gcattttctc 19080 tgttgcaatg ttcccctttt ccctattaca atacctcctc cctctcccat acaataatct 19140 ttccaataaa gtctctcctt accaggttag aaaacaaatt aatagaggaa gcagacaaca 19200 agatctttct ttttcaaaac tgctgaatga taaaaatgcc tgacaattct gttgtaatcg 19260 attgctcaat aaattattgc tgactgattc atgtgctatg aatcagtact attctcagtg 19320 gtgggaattc agagataaaa atcctagttc ctgccttggg tgctcatgct ctgactctgg 19380 agtcagatga cccattttga ttcccgcctc tgcaacttac tagttctctg tgcttccatt 19440 tccttatcta taaaatgggg ataaaaatag gacctcctcc acatggtttt tacaaagatt 19500 gagtcaatga gtcatgtata aagtgcttag actagtgcct agcacataat tagtgatact 19560 taagtgtttg ctcttactat tagttggatt aggctatttt tgcattgcta tgaagaaata 19620 cctgagactg ggtaatttat aaagaaaaga ggtttaattg gctcatggtt ctgcaggctg 19680 tacacacatg gcacactggc tctgctcggc ttctggggaa gcctcaagga gcttttactc 19740 atggcagaag gcaaagcagg agcaggcacg ttacatggtg aaagcaggag caaggggtga 19800 ggaggtgcca cacttttaca acaacaagat ctcgtgagaa gtcacccact gttgtgagga 19860 cagcaccaaa ccttgaggga tcctccccta tgacccaaac agctcccacc tggccctacc 19920 tccaacactg aagattacag ttcaacatga gatttggagg ggacatccaa actatatcat 19980 tccacccctg gcctccaaat ttcatgtcct tctcacatgt taaaatataa tcatcccttc 20040 tcaatagtcc cccaaagtct taactcattc cagcattaac tcaaaagtcc taagtcccag 20100 gtctcatcta gaaatgaatt ccttctacct ataagcctgt aaaatcaaac aagttatttc 20160 ctttcaagat acaatgggtg tatcagcatt gggcaaacat tcccatttga gaagggagaa 20220 attggccata agaaaggggc tacaggcccc aagcaagtct gaaacccaac agggcagtta 20280 ttaaatcata aagctccaaa atcatcttct ttgactccgt gtctcacatc cagagcacac 20340 tggtgcaagg ggtgggctcc caaggcctta ggcagctccg cctcagtagc ttttttatgc 20400 tgagattgca agctgatggt ggctctacca ttctggtgtc tcaaggacgg tggccttctt 20460 cccacagctc cactaggcag tgcctcagtg gggactcttt gtggagcctt cagctccgca 20520 tttcccctcc tcactgccct agtagagttt ctcttgaggg ctctgccctt ggagcaggct 20580 tctgctgggg cacttaggct ttctcataca tcatctgaaa tctaggtgga ggatgccaag 20640 cttccttcac tcttgcactc tgtgttcctg caggcttaac atcacatgga agctgccaaa 20700 gcttatggct tgcaccctcc agaggagtgg cctgaactgt acctgagccc ctttgagcca 20760 tgtctggagc tggagtggct gggatgtggg aaacagcaca gggaagtagt gcccctggcc 20820 tggtccctga aaccactcag tcctcttagg tctcagggcc tgtgatggaa ggggctgtct 20880 cagagatctc tgaaatgttt tcaaggcctt ttacccattg tcttgactct cagcacttgg 20940 cttcttttta gttatgcaaa tcgttttagc aatggttgct ctacagcctg cttgaattta 21000 tctccccaca aaaatatttt gttttgtttt gtttttgaga cagggtctct gttgccaggc 21060 tagagtgcgg tggcatgatc atggctcact gcagccttga cctcctgggc tcaagggttc 21120 cccctgcctc agcctcccaa gtatctagga ctacaggcaa gtgccaccat gcctggctaa 21180 tttttaactt tttttttttt tgagacagag tctccctatg ttgcccagac tgcggaaatg 21240 cttttctttc tctgccacat ggccaggttg caaattttcc aaacctctat gttctgcttc 21300 ccttttaaaa ataaggtcca actttaagtc atttttttac tcccacatct gagtgtaggc 21360 tgttagaagc agccaggcga catcttgaat gctttgctgc ctagaaatct ctgccagata 21420 tcctaaatca tcactctcaa gttcaaactt ccacagatcc ctggggtgtg aacacaatgc 21480 agccaagatc tttgctaagg cataacacat gtgaactttg ctccagtccc aataagttcc 21540 tcatttccat ctgagacctt ttcagcctga acttcactgt ccatgtcact gtcagcaatt 21600 tggtcacgat catttaatca gtctttaaga cattgcaaac tttccctcat cttcttgtct 21660 tcttctgagc cctccaaact cttcccttct ctgcccatta cccagtttca aagctgcttc 21720 cacattttcc agctatcttt atagcaatat ttgactctca gtaccaattt tctaaattag 21780 gttgttctta cattgctata aagaaataac cttcctgggc atggtggctc atacctgtaa 21840 tcctagcact ttgggaggcc aaggtgggtg gatcacttga ggtcaggagt ttgggaccag 21900 tctggctaac acagcaaaac cccacctcta ctaaacatac aaagattagc ctggcatggt 21960 ggtgcccacc tgtattccca gctagtcagg aggctaaggc aggagaattg cttgaacctg 22020 ggaggcagag gttgcagtga gccgagaaca tgccactata ctccagcctg ggtgacagag 22080 caaggccctg tctcaaaaaa aaagaagaaa gaaagaaaga cagggaggga gggagggagg 22140 gaggggagag agagagaaag agagagaaga aagaaaagaa agagggagag acctgagact 22200 gggtaattta cttaaaaaag aggtttaatt ggcctatagt tccacaggtt ctacaggaag 22260 catgatgctg gcatctgctt ggcttctggg gaggcctcag gaaacttata atcatggtgg 22320 aagtaagaga gggggagcag gcatgtcaca tggccagagc aggagcaaga gaggggagag 22380 gtgccacact ttacaacagc cagatctcgt gagaactcac tatctcgagg acagcactaa 22440 gccatgagga atccttccca tgacccaaac acctaccagg ccccacctac aacattgggg 22500 atcatatttc aacatgagat tttgagggga caccaaaact atattattgg tcttcgtaga 22560 ttaattgttt tagtctgtac aagtcaatat gtagaattat aaagatgaac cctgttgcta 22620 tatgaagaaa tctaagaaaa tacttgggtc ctcattttaa aaagccattt tgtatgtgtt 22680 ctatgcctga tgaaacactg tgtactgggt agagaaagtt tgtattttaa gctctcccac 22740 tggcaataat tagaagttga accaggatca gtatctaagt gtcccattgt ttgttgttgt 22800 tgttattttt aaatgaaatt ccttaagatg tgatggagac tctgcaaact atccaaaata 22860 gtgtcattcc aacatgttag caatatttag aattattaat gagatacttt acaatctttt 22920 tttatactgt ctttgaaatc ctgtgtgcat tttacactta tagaacattt catttcagac 22980 tagccacatt ttgaatgtgc aatagccaca tgtgtctagt ggctacccta ttagacagca 23040 taattccaac catactccca tgattttttg tttgtttgtt tgtttgtttg tttgtttttg 23100 agacagagtc tcattctgtc tcccaggctg gagtgcagtg gcgcgatctt ggctcactgc 23160 aacctttgtc tcccaggttc aagtgattct tctgcctcag cctcccccgt agctgggatt 23220 acaggcacgg ccaccacgcc tggctaattt tttgtatttt tagtagagac aaggtttcac 23280 catgttgacc aggctggtct cgaactcctg gtctcaagtg atccacccgc cttggcctcc 23340 caaagtgctg ggactacagg cgtgagccac catgcttggc cactcccatg atttataagc 23400 tccccagaca cactgccttg ccagtattca tgctgttgct tcagtcaaga atgaattcct 23460 cagcgctacc tctcttgacc ttcacatctt acttagtgca aatgctgtct cctcctgaga 23520 cttgcctgac ttcggatact ctccctgtta catcttattt aaaatgtcaa gtagactggg 23580 cacggtggct cacacctata atcccagcat tttggggggt tgaggtgggc agatcacttg 23640 agcttaggag ttcgagacta ggctgggcaa catagcaaaa ctccgtcttt aacaaaaata 23700 caaaaaatta gccaggcgtg gtggcatgtg cctgtggccc cagctacgtg ggaggctgag 23760 gtgggagcat cgcttgaacc tgggaggtgg aggttgcagt gagctgagat tgcaccactg 23820 cactccagcc tgggtaacag ggtaagaccc ccatctcaaa aaaaaaaaaa aaagtgtcaa 23880 gtataccact ttatagcact tgtaaagtgg tatgttgatg tggtttggtt gtgtccccac 23940 cagccaaatc tcagcttgaa ttgtagtttc cataatcccc acatgtcatg ggagggaccc 24000 aggggggtaa tttaatcacg ggggcagcta ccctcatgct gttctcttga tactgagtta 24060 gttctcacga gatctgatgg ttttataagg gactttttaa aaaacccttt tggttgggtg 24120 tggtggctga tgcctatatt cccagtgctt tgggaagtca aggtaggcag atcacttgag 24180 gtcaggagtt taagaccaat gtggccaaca taatgaaacc ctgtctctac taaaaataca 24240 aaaagaaaaa aaaattagct gggtgtggtg gcacacaccg gctaaggcag gagaatcact 24300 tgaaccccgg aggcagaggt tgcagtgagc tgagatcacg ccaccgaatg ccagcctggg 24360 cgaccgagca agactttgtc tcaaacaaca acaacaacaa caacaacaga caaacaaaaa 24420 cccttttgct gggcacttct ccttgctgct gccacgtgaa aaaggacgtg tttgtgtccc 24480 cttctgccat gactgtaagt ttcctgaggc ctccccagcc atgctgagct gtgagtcaat 24540 taaacctctt tcctttataa atgactcagt ctcaggtatg tccttattag cagcatgaga 24600 acagactaat aaatatgtgc atccattatg acagtgacta attgcatttt aataattggc 24660 ttaggtatct gtctttcttc ccaatgtact ggaagctcca tggggtgcag tgaccaagtc 24720 ctttggtctc tgactgtcta ctatttaatg aatatttgtg gaatatgtaa attaaacatc 24780 ttcaactgtg gtttaaattc ataggacaca tggaaaaact aacactatag gacacaatta 24840 ttaaaaagta tttaaaagta atgacaaaaa acgcagttac tttgcaccca cctaatagcc 24900 ggaaccatag gacttagttc aggaaaccca aatataggtt caagaaaggg gaatcaggcc 24960 ctgaaaatga atggctttgt taggaatatg catatgtgca gtgcaggctg ctaagagctc 25020 cttacagggc tgagtgggtc gtgagatctg ggatttgtag aaaaacatgg ctttttaggg 25080 agctgtccaa accttctatg gggcctgtta gtctctacat gtgccttttg cggtcattca 25140 ctggatttga tttctgtcac ttgtggcttt atgatgctat tgtttaggct ggataagaca 25200 gaacattcca gaagcttctg ctccagtgtt ttctcccaac tgagtcagct gactccatca 25260 attgtatgcc agggggcctg gggcaaagga aggggagggc atgtagcccc tttcgccagt 25320 tagtacagat tggtgtggtg gtgggaaacc tctgagatgg ggaagggcca agcaagactg 25380 tggagggcct aactcatctg acacaggatt tacagtggca catttcccaa acctttcaca 25440 tactggggag ttcagaatag taatgttttt ggaaaaagat gatgggcatt ccaaatgttg 25500 ataacagcca gtcagtctgg tttaaggaat gaagtgtatt atttacattt ttgtaaagct 25560 gcagattgag cagccctgga atgggtctgt gaatacaagg ctcattggcc tcatgatcct 25620 tttgctcagg gacatatttg tataaaattt gtatcaaagt tgtggtatcc catggcttct 25680 gcagcctttt tgaggtttat tttttatctt gtcagatacc tttttctatt ttgcctacca 25740 tttaacattt caagaattaa aaaagaaaac aatttgtcta agggcacttc caattaattt 25800 gcgtatttct aagaagtatt tactaaattt acagtatccc gtgaaatatc ttattttggg 25860 gtttcttagt tttgctgttt ggattattca tttctatttt aggcttgtat tatttaaaaa 25920 gatgtaaggg ctagatctta agttatttta ttattcattg ataacaagta atactggatt 25980 ttcaaatata atcaacatat ataatatata cagcattatc tttaagagtg tagactatat 26040 tttatattat aaaaattaca catatatatg tgttccatat atataatcac taaagatcaa 26100 cttgaaaatg cagtaaagtt ttgaacaaaa actactaatc catggcttca ctgtctcaaa 26160 aataaccaat gctaactaac attttagtgg atatcttctt ggccattttt ccatggatga 26220 gttttagatg gttatcatac tatgtacata tgcatgtaca tatacaaaat atacatattt 26280 tttattcacc taatgttata gcataggatt tttcaatgtt atattttggt cttcatacaa 26340 atgaatttta atgatgatta tatttaatag agtaaatgta ttactacact taactgttcc 26400 tttcctgaac atgtagatcc gttttcattt tctcctctgg ttacctcgtg ggttgaatgt 26460 tctcctcatg tttgccagcc agttgtgttt ccacactttt agttcttgtc ctttgtccat 26520 ttgcttatct gggttctgga gtgttcatgg cactctgtga accttttatg tttcatttgg 26580 ggcaactgct tttccattgt ttaccttgtc aatttttaaa atgtgttgta gtcaagtcta 26640 ttctttttca acatttctat caggtctgag ctttaaaagt cttactccct tcaatggttt 26700 gatgttcaag tcgattttct tatagttctg tttttccaca tttaatttct tcaggatcta 26760 agtgtcttcc ttgcaattta gcaaaggcag gaattttgtt tatactgtct aattctgtcc 26820 tattaaccct ttagttcttt aaccgtgtct gagccaagct gtataagaaa tttttttaac 26880 ataaagagac aacaaaaaat ttaggaacac cgtgatcatt gtttccatta ttataggaga 26940 atgctttctc cttttttcta aacttgcctc gcttttctct gatagtgttt ttagattggt 27000 agctaaaact gtatttgttt tgccaaaata gaaacagatt ttgaaaaaaa aaatccttaa 27060 actgctcaga agtaaaaaaa aatagaaaaa gatctctcac accatcttat catgcacaaa 27120 aggttgtgac caggtatgtg tgagttttaa atgcacgtgg tacattaggt gaattgccta 27180 cgtgagccta tgggtcactg cctggggaca gggagaccag ggagatattt ccatcttaag 27240 gagtgaaact gtttcttgca cactgtcaac aagcgggtga gtcttctccc gaccctgctc 27300 ttaccacttc ttctcagtat cctgctttgt atctacaggt tgctgccttc agttacctga 27360 gcgggcagcg tactcaaagt taagggtaga ggctcctcag cctgtgcctt tggctggctc 27420 cccttgcttt ccctcttctc tgtggtcacc ctaggacttc agtactcctt tcacgttgat 27480 gtgttcatca ccccagcctc gcctggatct gtgatggtct tttaaagcgt gtcctcctcc 27540 tccaggacca cagctttctc actccccaca tgggaatgct ttcatgcttg ctgcccacct 27600 tcgccccacc gctgcctctg ttggaacacc cccttcaccc tcccacctgc agaagcccac 27660 tctttccaga atcaagcaaa agtgtctttt gcaggagtcc ccttccagtt gccatccctc 27720 cctcctctgt atgcccacag tgcgtttact gtgaaggagg tggcctctga aggcagtctc 27780 ccatgctcta ctgtggattc ttggaggacc agaaccagga cttaatgtca caccatctca 27840 agagcttagc acaagccgtt gcacatggta tcagtagcta atccctccta agcagcaggt 27900 gtgccaggta gtgttgtaac tggatttatg tggatttcat tctcacaaca accctacaag 27960 gtgagtacgt tattacctcc attttacaga tgaggaaact gaggcacaga agcagtgagt 28020 aagatgaaac cagggttgaa tgttaaccct accagccaga tctcagtcta gtttgtatcc 28080 agtgtatgcc caatcacttc ttaatagtaa ttctcaacag aggattaggt gaatgaagga 28140 accaatatga ctgaaagata acgatactat gatagtatta tacgcatcca atttatcaaa 28200 cacctctgag gaattagata taccgatgtt aattttccac ctaattaaaa ttattccttt 28260 tgatttccac tccttatctc agtctattgt ttctaaaatt atttctaaaa ccaaccatga 28320 attttcctgc ctgattaaat agttcatgga gcataactga accttgtctt aatgacaagg 28380 accgtcatag taatgcacaa atgttatact atagtctgag attcattagc atctactaaa 28440 taccagggac catgccgggc acttttaagt atagttcctt gattaattgc ctaggctgaa 28500 aatttgattt gttttttgtt gttgtttttg ttttgttttt tcaaactctt ctttgtattt 28560 ctgaaagttc atttggtctt ctttgatctt gtaggacagt aactgatcaa tatgcccctc 28620 tctgcaggca ccagccttgg cttacacaaa agtttggctt tgaaatttcc tctcctcctc 28680 catattccaa taaattactg tgaattaacc tctgtgtaaa atcaaggaat accctgaatg 28740 agaggtgagg tcaccaggat tctaaacctg gccctgacac tttcgattgg tcctgaatcc 28800 acatatcctt atctataaaa aggtggagtt aatgatttct aagtgaaggg tctttggtta 28860 taagcaaaat aaactacctc tggctaattt aagtaaaacg ggaatctatt tgaaggctat 28920 aaagtaggtt aacagaatca aggaaagcag cttggaagac aaaagcagga tgcagggcag 28980 ctttaaagat ccaggtcacg agagtgtatt gatcatcaca tcatgtgtct gccactggga 29040 ggaatcctgt cttttactga gttttcttgt ttttaaatta aaattttttt tttttttggt 29100 agagacaaag tcttgctctg ttgctcatgc tggaatgcag tggcatgatc atagctcact 29160 gtaacgtcaa actcctgggc tcaagccatc ctcccacctt agcctcccaa gtagctgaca 29220 ctacaggtac atgtcaccac gcctggttct tttactgtgt tttctatctt gaggcactgt 29280 gctcaggatt cagaggccag aggaaaggaa ttggttgagc tcaggtccca tagcaacctt 29340 gactgatggt cttacacagc tgtacaatac aagagaggaa agcaaatcag ggctattacc 29400 agcagaaagc ggaatggttg tctaacaaat gaaaagtcca ctgcaaacac tgaacttcaa 29460 gctgtgtaag tggtttaaca cggaagtgtc tatcaaattt ttaaatatat tctttgtaaa 29520 ctggaagggc atgtaattta tcattagatt tggctttggt tagaggcatt tgttagaggc 29580 attagctggt ttcatcctac aggcgtttct taggtacctg ttaggagagg ttgtctcata 29640 cagagagagg agcaccttgt gctaatgaga aagacttggg atcaagttct cactcttctg 29700 cctgtgctct gtgtccccag ctgtgaagtg gggcaatact acatgctgta tttgtactac 29760 atacttgtaa ggattaaata aaataaaata atgtgggtta aactctttga agagctatgc 29820 aagggtcagc tatttatagg attagtgggc atagcttggt gcttagtgtg atatgatgtg 29880 tgatatgtgt atatgtgata ggaagtatgc ttccttctat acacttgaca gagtatagga 29940 tatagacatg tgatatgatg aaatatatat ttagtcttcc tccatttcct ggcatacagc 30000 tcctaagatc cttggaatcg cttaagtgat aagtgtcttt ttgtatgcta gtgaattgac 30060 tgatgactgg cagcctctat ggctcctgga tgggagctgg tcctgaaaga agaggacagg 30120 attagagggt tgggactttc agccccaccc cccaacctcc caggagggga gaggggctga 30180 aagttgggtt gatcacaaat ggccagtgat ttaatcaatc atgcctatgt aatgtagctt 30240 ccataaaaaa ccaaaaggac tgaatttgga gagtttccag agaaccaaac atggggaggt 30300 tcctggagag tagcgagcct gcagagggca tggaagttct gagctccttc ccctacacct 30360 tgcccagtgc atctcttcat ctgtatactt tgtaatatcc tttataataa aatgtaagtg 30420 tttccctgag tactctgggc tgttctagca aattaattga gcccaagcac agggggatgg 30480 gaaccccaat ttatagccat tagttcagaa gcacaggtaa aacagcctgg ggcttttgat 30540 tggcatagga ggtggaaggc agtctcaacc tgtagaatct gatgctatgt ccaagtagaa 30600 agtatcagaa ttgaattgaa ttggaggaca ctgcagaatt attggtgcag agaaaacgcc 30660 acacacttct tggtgaccag aagtctcaga agtcttagaa gtcttctgtg taagttgtta 30720 cagtatgaga gcacagaaaa aaatggtttg ttttttctac tggagaagat acaaagactc 30780 atctatttgt atgcatctat atgaatgcat ttattttctc atctgttttt attttaaagt 30840 ctagaaggga tttaagaggt ataaagagat acaatataca gacagtcctt gacttatgat 30900 ggttcaactt gaatgatgtt ttgacttcgc gattgtgtga aagtgatgta tttggcatgc 30960 ccctccaatg acgatagagt tacatccaga taaacccatt gtaaattgga aagatactaa 31020 gttgttgaat caaaaacaaa ctttcaactt acgatgtttt caacttatga tgggtttact 31080 gggacataac tccatcatca ccgaggcgca tttttacgta ccagtttcag ccttcagctt 31140 gcttgcagtc tacctgaggc tacatgataa tttcacaatc taaatgatgt cactcagaag 31200 tttctaattg aatgctaaag acatgtacgg acatccacag gtgggtgaga aaaatccctg 31260 tgctgctatg gttgggaaag gcctcagagg aggtgtgggt agcccagctg gccaatgcct 31320 tcctaacctg tgctcttaaa ttagctctgt tcaatagaaa tattacatga accacatgtg 31380 taatttaaga ttttaagatt ttctagtagc cacatttttt aaaaagtaga aggaagcagg 31440 taaaattaat tttgataata tattttaatt ttacccatta taactgaaat agcatcattt 31500 caatatataa tcaatataaa aaaaggttgg cactgttttt gaaattctgt atatatttta 31560 cacttacagc aaatctcaat tccagttagc cacagtttaa gtactcagta gtcacatgtg 31620 actagtggct accatgtcag acataataac cctagctggt ttaggaagaa ggaaagataa 31680 gcaaagggaa agaaacaaaa gtcactggaa tttattgaac acctactatg taccaggcag 31740 ggctagggct agggctagtg tgaggcattt gatgaacaaa agatcagatt ctgtttttat 31800 ttaaaatttt gttcatcata aatttttggc ataaattttg gttttaataa atagtgcatt 31860 aaactattta tcttgattac tacttgttta ggcacctctt acatcactca cactgactct 31920 aggcccagcc ctggcaccag gcgctttcta agaactttct aatgcttcat ttgggggctc 31980 taacttgaac caaactgtgc tgtatatcag aaacagagac cgggtgtggt agctcatgcc 32040 tgtaatgcca gcattttgga aggtcgaggc aggaggatca cttgagtcca ggagttcaag 32100 accagcctgg gtagcatagt aagacctcat ctctacaaaa aaataaaaca attagctggg 32160 tgtggtggca tgcttctgta cttctagcta cttgggaggc tgaggtggga ggattgtttg 32220 agcccaggag gctgaggctg cagtgagctg tagtcatgcc actgcactcc agcctgggca 32280 acagagcgag accctatctc aaaaaaagaa acaggagtga actcctgtaa tttactaagc 32340 cttgggcatt attttttaaa ataaaatttc aatttaattc aatgtagaaa caagaagaca 32400 ttggtaaaca aattgaaatt caaactaaat ctgtgaacca aactgaaaat tttgaaaata 32460 cttcaggacc aaaccataac ccaggagaga gttcatcggc tttgattccc ggtcaaggtg 32520 accctcaact attgcacctc cctaatcagg gaagaaaaga aggaaaacaa agtttttgag 32580 aagactctat cctaggcctc gtttccttcc cacattatag cttcgatctc cagcttttta 32640 aggcttagta gctgcagtct ctatataatg ttatattggg aatgttatat tgaaaatata 32700 acttggatgc tgaaagaaag gaaaagtctt gcttattaaa gtggtgtcta ttttcaaata 32760 aaaccctttt ctttctttta gggaactcag aaacaaagca aatattcaat ttggagataa 32820 tggaacaaca atatctgctg ttagcaacaa ggcctatgtt tttgaacgag accaatctgt 32880 tggagaccct aaaattgact taattagaac attaaatatt cctgtattgg taagtaggca 32940 ttttaatacc attaagttgg attttggaag aaaggaaaaa gctaagttaa tgctctttat 33000 gattttacat ttaggagcca ttaagttatg ttgaaatata catatataaa aagaaaaata 33060 cttcttttct tttctttaaa gtacatcttg gacttttttc taagatgtat caaataaggt 33120 cttttcaaat gatgacaaaa ttcagatttt aggatttgtt ttcataattt cttcctgggt 33180 gttcaggatt agcaattgtg caaataaata tgcccctagg attttttggt agctaataat 33240 tttaaaaatg tttatttgcc ccttgttttc attcagaaat tctagcaatg aaatttgtat 33300 accatttctt acttcagatt tttatgttgg attttatact ctcaaaattc ataaattgac 33360 accagaaatc aatagactgg cagcctactg tgatttcagt gggctctgtt tataatggta 33420 attctaccta ataacgacac ctattctaca tctattctat actgagaccc atgagacttt 33480 cttttttttt aaattaaatt aatttattta ttattaattt tttttgagac agggtcttgc 33540 tctgtcgccc aggctggagt gcagtcagtg gctccatcac agctcactga agcttctacc 33600 tcctgggctc cagggatcct cctgtgtcgg ccagggactc caggcgtgaa ccactgttcc 33660 tgggctggcc cagtaaacat tctaattcac ctacaccaac ccctgccgac tctcccaccc 33720 taacccctag gtgaccgctc catatgcagc tggacactga tgatggaccc aggacctaga 33780 cagtatgagg tccctgccac ctagtcccag gggtgtaggt cgggtttata atgagcctct 33840 ggccctgctt aggcggaagg tagcgccacc ttgtggccaa agatgcccac atgtttacaa 33900 gagcttttcc ccttttgtgg tgtctggata actcagagcc tgcaaatggt ctctttgtaa 33960 atattacact tacaaaatgc agtactggga aaggacagag aagaggcttt gtcttccata 34020 tgcagccaga aaggagctca ctgcctgatt tttcagctat ttaatctcaa cctttacatt 34080 tatatttcca accccctttg ctatggggta gtaggagaga gtggatggag gtgctttgga 34140 ggggatgctg ctgtcttaat atacctctgc tccgcagact gtcatagagt ggtcccaggt 34200 gcacttcctc agggagatca tcgaggccat gttgaaagcc tatcagcaga agctctttgt 34260 gactcacaca gttgacgaat tgctctgggg ctacaaagat gaaatcttgt cccttatcca 34320 tgttttcagg cccgatatct ctccctattt tggcctattc tatgaggtaa gtagattttt 34380 cttttcagaa cctctttttt tagctgacag tgggttgggg caccccaagc cagattaact 34440 ttgagtttct tctagaaatt gcctagagtt aagttatctt atagagtgtg tgaaaaatgg 34500 agtgtttttt ggaaagaaaa aaaacttgag gccgggtgcg gtggctaatg cctgtaattc 34560 caggactttg ggagaccgag gtgggtggat catttgaggt taagactttg agaccagcct 34620 ggccaacatg gcaaaactct atctctacta aaaatacaaa aattagccag ctgtggtgat 34680 gtacacctgt aatctcacct actcaggaga ctgaggcagg taagttgcat gaacccagga 34740 ggcagaggtt gcagtgagct gaaattacac cactgtactc cagccagggt gacagagcaa 34800 gactctgtct aaaaaagcca aaaaaaaaac aaaaacaaaa acaaaaacaa aaaccctgga 34860 gtgcagtgga tagttgggaa gttggtaaaa gataaaataa ccccaggaag aggattagat 34920 taggggtgtg ctctgggatt gtgatgggtc tcctcagctt taaatttgta gctgttttct 34980 ggctctgcct gttcaagagt cttaccctct tcatgtaatc ctgtagcatt ccagttttta 35040 tggcaaacag caataattgt gtccctgggc cttcaaggtt atataaaacg tagaaattgt 35100 taaaatagaa ttgtgagcaa gttttaaaaa attatatgtg tgagagacag gagtcctaaa 35160 agtagggcct caccaactct gaatgcatca ttcgggagaa gcagaccagg caggagttcc 35220 ctagagggtc ctgtctcaga ggaatacagc ttcacaggac cagaggaagc acagatttcc 35280 tgtcaagccc tgactgaacc tcccttctag aaataatttc aggagagcct cctactgaga 35340 gatattatgc aaaggttccc tcgaggccct tttgttccca gtggcttcaa tccatcagcc 35400 aagtagatct tgttgctaat atctcactgt ttctcagata atttgcatta tataactcac 35460 tttttttgtt tttacatcat tgaattcacc agactgatag ccacactatc ttatgtggtt 35520 gtgaggattt catgagatga ttcatgcaaa aattttagaa cagagccagg aatattatac 35580 tcaacaattg ttcactccta ttattataga ggagctacta cctgtgctat ttctgagaaa 35640 tcatagctac atgcccaaat aaagaatttt aggaatgtag tgtctgtatg tgcccttaag 35700 aagtataact tggagagaat atacaattga agaaacctta attgaaaata gggctatatt 35760 aataccgtct tcttccagtg tagctattct ggtataattg gtcctggtcc tggacttagg 35820 cttttaaatt tgttattatt gagaaataat tcacttacta taacatttac cattttaaaa 35880 tgtacaattc agtagtcctt agtatagtca caaggttgtg caaccattac tgctaattcc 35940 agaacatttt cattatccca aaaaagaaac tgcatactct cttagcagtc actcctattc 36000 ctgtcttact ctcccaggcc ctggcaacca ctaatctact ttctggctct gtgaatttgc 36060 atattctgga catctcatat aaatggagtc atataatata tgcccttctg tgtctgcttt 36120 ttaaatttag tgtaatgttg tcagggttca tccatgttgt agcatgtatc agtgttccat 36180 tcctttttat aactgaggaa tattccgttg tgtagatata ccacattttg cttatccatt 36240 tatcagttga tggacatttg ggttgtgttc cttcttggct attattagaa gtgctgctat 36300 gaatatttgt tcatacaagc ttttatatga acattgggta tataccttga agtggaattc 36360 tcttgagtat atacataggt gtggaatttt ggagtcctat gaattctgtt taactttgtt 36420 aagaactgac aaactgtttt ctgcagtgac tgcaacattt ttatattcct gctagcaatg 36480 tataaaggtt ccaatttctc cacatcctca ccaacgctta ctatttttct tttttttttt 36540 tttaattgcc ctcctagtgg gtgtgaagtg gtatctcatt gtggttttga tttgcatttc 36600 cctaatgact aatgatgctg aacatgtttt tatgtgctct ctggccatta gtatattttc 36660 ttttcagaaa tgtctcttca aatcctttgc ccattttaaa attgagctcc tactttttaa 36720 aaccataaaa taataatatg gttaatatag tatttagcaa aatagtcact attttctggt 36780 cctggttcag tcttgtgtag cagttaggcc ctagtaggac agttagatga agattaaatt 36840 ttttagttac tgtatcagtt agggttgcca gagaaactga atcaagaggg tgtatatgta 36900 gagatgagaa agagggagag aaagaaattt atattatgga attggcttat gtgattatgg 36960 gagctggtaa gtctgaaatc catagagcag gccagcagct ggaaactcag gtaaaagttg 37020 atgatgtggt cttgagtttg aaatctgtag ggtgggctgc aacctggaaa tccaggcaga 37080 atttcgatgt tgcagtcttg aggagaattc ctcctctaag aaacctctgt ttttgcttgt 37140 aaggctttga acagattgga gggggcccag ccactcatta ttgagggtaa cctcccttaa 37200 agttaacgga ttgtagatat taatcacacc tacaaaatac cttcaccaca ccatctgggc 37260 tagtgtttga ccaaacaact gggcaccata gtctagccaa gttgtcataa aattatcaca 37320 gttactttaa atgatcatat tcacatattt tcagaaaaat gggactaatg atggagacta 37380 tgtttttcta actggagaag acagttacct taactttaca aaaattgtgg aatggaatgg 37440 gaaaacgtaa gtcaaatgat ttatcagtgg aattattttt tcagttttca tttaaactac 37500 atgtctactt ctacattgct taaaaatgtg tttagccttt tttggatgaa aaatataaaa 37560 acatgtaaat agtcttgtaa ttattattct acaaatcaag atggtggtaa aacatcttac 37620 agattaaata ttagtgattt gtagatttat catggccagg catgaattac aggccagtga 37680 aaagtcccac tcttgcttag tagtcattga gtgatgtgta gtagctacag cacaaatact 37740 tttcaaacca ccacatgttt tgggctattt ggccattgcc tctatgaaag ctgatttggg 37800 ccagggacct actttttctc ccccttgatc taattaaaac tgttgtgtct gtgtatgaat 37860 aagatactgt ggatagacag ctccagttaa atcttgcaaa gtcctgacca tttaagagaa 37920 tctaaactca aatgtgatca tctttactct ttcttgtgct tatcaattat aggtcacttg 37980 actggtggat aacagacaag tgcaatatga ttaatggaac agatggagat tcttttcacc 38040 cactaataac caaagatgag gtcctttatg tcttcccatc tgacttttgc aggtaaaagc 38100 tttaaagata agttcttttt caaaaataag gtctttcact gcaagaccac caaaagcatg 38160 aggaatatat gcagacacac ttattatgca tggatattta tgcataatca gtgataaatg 38220 ctgatggcac atcgagacag tatagtgtac tggttcacag cacagacttc tgactgttgg 38280 tttgaatctt ggctctacca cttatagctg tgtgaccttg ggcaaattac ttaaccactc 38340 tgtacctcac tttccttatt tgtaaaacaa agatagaaat tgttaactat gttagaggtt 38400 gttatgagga caaatgagtt agtattagtc aaatacttag cccagggccc atcacacagt 38460 aaccaatatt aagtgttggc tcttagttac tatgatatgc tctgtcaagc atcaactgac 38520 ctggtctact tccagtcaat aggtagtctc tacatggaag ccaaataaaa gatactgttg 38580 tccatatttc agcagagtgg tttcctcagg ggaggcagag aaggaatgga atcaagagca 38640 ttacgtagac aggttcagtt atatccataa tataattttt atttgtctaa gtggcagata 38700 caaaggtatt tgttagagta ttttatctct ttctggtgcc taaaattttt cattaaaaaa 38760 tgctgtaggg gtggtttggt ttgtgcagtg aaaccaccta tgttattcac aaccttgcga 38820 gagatgtatc aacagctctg gttcagagat gaaaaagtga ggcccagaag gctcttccgg 38880 ccagccttca aaggaagggc tgaaggctca gtggtgactg tgtacatcaa agtggttagg 38940 cactatgcag tgtaagcagt ggtcatatta catgggacta tgtttgaaat cagtaagaat 39000 gaaaggcaga attacgttga actccattta aataaatgac tggggcaaaa tatggaatct 39060 gatttttctt ggaggggggg attgagtatc aaagtgtgta ttccaataaa gtatctgtcc 39120 aatgtgacac ttttcaagtg cctaagaccc tacgaggcca cggccatcgc tgcctgttct 39180 accttagctt tggctctgcc gtgccctggc ttccctggct ttgccggtgg cccgtccaca 39240 ctggcatatg tccatgcagg tctagagagg cctcttattt cttttttatg tgagtctcca 39300 ttctaaatgt tatcatctta attttgtacc acatattgtt ttttcttgtt tggatgatat 39360 caccgttgct acaataaaca ccttccacta caattcatct tctgctttat tacacgttga 39420 gttgacagaa tgccttccaa acattccttt ctacttaccc tgtgagcttt tggccatgtt 39480 gtacctgaga actgttgcta acttgcggat ttcgggcaga ttacactgac cagagtccac 39540 attcactttt tattcttaca tcctaacagg tcagtgtata ttactttcag tgactatgag 39600 agtgtacagg gactgcctgc ctttcggtat aaagttcctg cagaaatatt agccaatacg 39660 tcagacaatg ccggcttctg tatacctgag ggaaactgcc tgggctcagg agttctgaat 39720 gtcagcatct gcaagaatgg taagaactca gagaggggac atgatagggg tgtcaagaat 39780 gcagaaggat tggagttcaa caaagaatat gtagctgggc gtagtggcgc acacctacag 39840 tcccagctac taaggatgct gaggtgggat gatcacttga gcccaggagt tctcaagtcc 39900 atcctgggca acatggcgag accactgtct ctaaaaaaca aaacaaacaa aaaagaatat 39960 attgtcagcc caatagaaag atcagtttct ttcaagaaca atgtttcata acatggctat 40020 tgaatggtaa aaaaaaatca tggcttttct gtgatgcttt ttatttctag aatgccatgt 40080 tgtgtttttt tttctggaca gtggtttaga agtcttaaca gtaataatag ctcatgttta 40140 ctaagcacct gatgtatgcc agtcactgtc ctaagtgctt tacatattta catgtagtta 40200 atgcatgcaa aacattaact gatttcatgt tcaaaacaat gctaaggctg ggcacggtgg 40260 ctcatgcttg tattcccagc actttgagag gccgagatgt gaggattgct tgaggccagg 40320 ggttcaagat cagcctgggc aacatagcaa gaccctgtct ctacaaaaaa aaaaaaatta 40380 aaaaattagc tgggtgtggc ggcacacacc tgtagttaca gctgctcagg aggctgaggc 40440 agagagattg cttgaaccca ggagttcgag gttgcactgt gctatgattg tgctgctgca 40500 ctccagcctg ggcaatagag tgattccgca cctccccacc aaaaaaaaaa aaaagctaaa 40560 agaaaaagtg gacaactcag ttttaagaaa gtacgtatca tggcaaagat tctcagtgat 40620 tttgaagcag agttagtttt aaaccctgac acaaatgtcc cagtgtttct taatgtcaga 40680 gctactctgc tcctttccat gaatgaggca gaattatcag tggcacaact gacaaaacta 40740 ttttcttcat cttgaagagt agttttaaca gccacatgtt gcagaattat tcacaatgaa 40800 cttactagat agtagacatt cagcggcctg tttttataat tggggaaact agggctcaga 40860 gagggaacgt gattttgatg cgactcctcc ctctgagcag atccctggcg gaactcaggg 40920 tcttctcata tttgccctgt gattccctct tgggctgtaa ttcctcttta aaatttctct 40980 ggagagctct ctgtgtagtc cctttctcct gaatagtaat gtgctcactt ttgctccctt 41040 atctatctca ttttaaaatc tcctttcagg cctggcatgg tggcgtgtgc ctgtagaccc 41100 agctactcag gaggctatgg tggaagggtc gtttgagccc agtttgattc tagcctgggc 41160 aacatagcga gactccatct tttaaaaaag aaaaaaaaaa aaagaataag atatcatttt 41220 ggaataagtc tgaagtcagc agtatacctc ctgatccttg tctgacaggg cagtgacccc 41280 cacacctggc tttacatcag aattatctgg agagttatta aaaatatatt ggtgaggcat 41340 ggtggatcat gcctgtaatc ctaacacttt aggaggctga agcaggaggc tcacttgagg 41400 ccaagaattt agacctgcat gggcaacagg gagaccccat ctgaacaaaa aatttaaaaa 41460 ttagctgggc atagtagcat acacctatag ttccagatac ccaggaggct gaggctggag 41520 cgtaggaatt caaggctgca gtgagctatg attgcaacac tgcactccag cctgggcaac 41580 agagtgagac ctggtctcaa aaaacaaaaa aattatatat atataaaaaa ttgtttatat 41640 atacgtatat catatatatg tgtatatata catatatata tacaactgac aaaagtattt 41700 ttcatcttga agactagttt taacagccac atgtatatat ttatgtatgt atatgttaat 41760 atatttgtta atatatgagt atattaacaa attttatagt tatatataaa tatgcatata 41820 tttgcatata cttatatttg ctatatttta atatatatgt atatagtata tatatatagg 41880 tatacacaca cacgtgcgca agtgtgcaca cacactcatg gtgcacacac atgcatgtat 41940 gtcccagggt cccatgttgg atataccagg gccccagaat ctacactttt aacaagtact 42000 ccagctgatt tccataaaga tggcgtctag gtatttgggg accattgtgc aagggaacat 42060 ggtacccttt acctggagat aaagaccaag ggtgaatggg aacaagttcc tggttgtgat 42120 ctcccccatt gccttactgg taatagtcct gaaacagtgt ccctgccccc tcatctggtg 42180 tgcatctggc tcaaagcaaa aatgtagata tattttctct tgctgttttt attaaattct 42240 gtttccttaa gaagctgatg ccagaatcaa cagaagtatt ctactttaca catttaaact 42300 tcttgctaca atccttttcc tcttccctct taacgtattc ccgaatttgg actgaagtga 42360 aactccccag gattatcctc cagtgttttg aattctccag ggaaacattt tggatagcag 42420 gatgagtgtt ctggagtcag gcagattggg tttgagtcct attctatttg ttggtaaatt 42480 ggccaaagtt tattaaggag ggttccagac atcagttttc tcattaataa aatggaggtg 42540 gttatagctt cttgaggttg tgtgagagtt agaaataata tatataaaac actcaggaca 42600 gtagccccta ttaagccctc aacagattta aaaaatacat tttcaaggtc attataggtc 42660 acaaagaagg aagtcatgcc tttgtggaac tattcagcag taaacagcaa aatgcatgtg 42720 catgtgagag atgagggatg agttccttaa gccatgggct ggtgaatatg taagcaaatt 42780 taaataactt gccgacaagc tcctttctcc aaaaatgtat ttccctggca gcaattgttg 42840 ggtccctctc ttcttttcaa tagccagatc tagaataggt ttcctttagt aacttgtttc 42900 cctatttggt tatatatata tatatatata tatatattta aatttacata agcacttatt 42960 tggttcttaa aatgaatagg aaaggaaaaa ccccagaatc tttgtgatct ggttagaggc 43020 tgggtgtata gcacaaccag gctaactctt aaaaaattat gtaggccagg tgtggtggct 43080 caagcctgta atctcagcac tttgggaggc tgaggcgggc agatcacttg aggtaaggag 43140 ttcaagacca gccttgccaa catggtgaaa cgctgtctct actaaaaata caaaaaaatt 43200 atccgggtgt ggtggtgcat gcctgtagtc ccagctactt gggaggctga ggcaggagaa 43260 ttgcttgaac ctgggaggcg gaggctgcag tgagctgaga ttatgcctgt ctttggtaaa 43320 aacaaaacaa aacaaaacaa aaaaccacca aaaatttttt tttaatttta aaaaggacaa 43380 gaaataaaaa gtcagtccac ttactgatag agaattgtag ttgaaactag tgctttgagg 43440 tacaacaccc ttcattcact tagtattctg ccttcatagc ctgatggcta gctgtccctg 43500 ggtaaatttt gtaacttcta tgaacctcac tttcttcaaa tgcaaagtga ggctaatagt 43560 tctgacttta ctgggctgtt gggagcatta aataaaataa tgtgtatgaa gcacttatac 43620 tttaacttca gtaaatattt gttgaagaat aaataattta gcctgaactt caatatataa 43680 tgtggaataa aaaattgggg gtaaatgaga tgtcagaaaa tgaagtataa atcctgaact 43740 aggaggtaaa ggatggtgtt ttagcctacc caagttaatt tatatgtagc ttttttgttt 43800 ttctttagga accaggctgt ggccaggaac ttttatattc agctcagctt agattttaaa 43860 aacagcatca ttcatttctg ttttccttca aatgcaggtg cacccatcat tatgtctttc 43920 ccacactttt accaagcaga tgagaggttt gtttctgcca tagaaggcat gcacccaaat 43980 caggaagacc atgagacatt tgtggacatt aatcctgtga gtacatactt cctcctggta 44040 aaagagcata tgttttattc tgtctataca ttgttcacca gtttagtcct gagccttctt 44100 taaaaatatc cttactttca tatacatatt caagtgggag aaattcagct cagtgctgat 44160 ggaggcattg tctcatagcc ctgtaattag aaggctgaat tttgtggatt gaatagcaga 44220 aatacgagca aacctgcctt taacaaaaag caacagtgaa aactcagtta ttggaaacta 44280 ctgatgtacc catataacct ggtcaatctt ctgatgctag ccttggacct caacatatat 44340 ttatttctcc ccttgggaca cagatcgata aggttaaaga tgtccctttg cttcctcact 44400 gccaggaata ttttggttga aatatgaata tgtatattaa cctcagtcac ttttggcaaa 44460 cttctttcta caggttattt gagagtttat tatattatta attgtaaagg tatcagatat 44520 acatagagga gacatacaca cgtgtgtgtg tgtgtgtgtg tgtgtataat acacatttac 44580 tcctgtattc atagacgaga aaaacaaaaa ccatgctaac catgtcttca tttttggaat 44640 ttgaacatta tggaccaata aaaaaaaaaa acaagaacat tcttttagca cagtatttta 44700 tgggtacttc acactcttag ctgcatacat tgcatttgta tctgagaaac cagtgatctt 44760 atgctctggt gaataaaatc gtgtgtggtt ttctcccttt tctcttagcc atcagctgat 44820 cagttccctt ggatcagcca aactgttagc agtgcttgtc accaagggac gaacacagtc 44880 ttataacctt agtgcaaaga tggagctgcc ctaaggatga caagtgctgc agctgtgccc 44940 catggctacg ctaggcgggc cctatactag gatgccactc tctggcagtg accaccaccc 45000 tcttcttagc tctctggaca actgcctgga aatccagacc tgacaggcta tcttttaggc 45060 ctccttcctg ttggatccct tctaaggctg tgctattcag agtggcagca tcctgggagc 45120 ttgttagaaa tggccagtct actgaatcag agcctgcatt ttaacaggat tcccaaggac 45180 ctacattcat actcatgttt gagacacact ggtctatcag ccacctaata caacccatgg 45240 ttctcattct gttctgggga tcacttttac ttgtttccac tctgcctgtc acacatggta 45300 atggtcacct tgtttatgag gactacacag aaatggtgct ctattgaaaa agttgtttgc 45360 agtttaataa atcctaatgt ttccttttca cttctctgat ttgcagttga ctggaataat 45420 cctaaaagca gccaagaggt tccaaatcaa catttatgtc aaaaaattag atgactttgt 45480 gtaagttttg cttctttcta tggaggggac agcagttttg ctccattgcc cgtctggtgg 45540 ggttgatgtc aggaggagta cagcctactt catctaagcc tgctcacccc tgcccttcag 45600 ggatggggca tgatcagcat tttcatgggt gccttggtct tggaatttac ttgttttatt 45660 taatcataca cttacagagt acttcccatg gatcaggtat tgttctcagc accttatgtg 45720 gattcacata taaccttgta ttatccccat tttacagatg aggaaacaga agcagagtgt 45780 ttaggtaact tggctaagcc ttactatcta gtcaactttt atccactcca ctaagccttt 45840 ccctcatgca ccttgactct cttggtgtat tagactgttc ttgtgttgct ataaagaaat 45900 acctggctgg gtacagtggc tcatgcctgt aatccagcac tttgggaggc caaggtgggt 45960 ggatcacaag gtcaggagat caagaccatc ctggccaaca tggtgaaacc tcgtctctac 46020 taaaaataca aaaattagct gggcatggtg gtgggtgcct ataatcccag ctattcggga 46080 ggctgaggca agagaatcgc ttgaaccagg gagtcggagg tcacagtgag ccaagatggt 46140 ggcactgcac tccagtctgg cgacagagca agactgtgtc tcaggaaaaa aaaaaaaagc 46200 gggggggggg agggagggag ggaaaggaaa ggaaatacct gagattggtt aatttataaa 46260 gagatttaat tggcttacag ttctgtaggc tgtacaggaa gcatggtgct ggcatctgct 46320 cagtttctag ggatgcctca gggagctttt gctcatggca gaaggagaag caggaataaa 46380 gcacgtcaca tggggtgagc aggagcaaga gagagaggag gggaggtgcc acacactttt 46440 aaataacaga tctcatgata actcactatc acaaggacag caccaagcga atggtgctaa 46500 accattcatg agaaatccac ccccatgatc cagtcactgc ctaccaagcc ccacctccaa 46560 cactggggat tacatttcac cctgagattt gggggaacaa gtatccaaac tatatcactc 46620 agagacttga gacagagtct cttcctcttc ctctctctct attcccactg atcccacttg 46680 gggccagcca tagctctcat ttgtatagtt ataatctctt gagtctagcc ttacttcccc 46740 atgctgcagc ttaatttgga ttccaaagta taatctcctg ctcagacttt tcaatgggaa 46800 ttttttagat atgagaaaat tatgatataa tgttgagtga aataaacagg atgcaaaact 46860 atgcataata tatttatcta taaaacttgg cttgtttacc tcattgaatt tgccagattt 46920 aataccaggt gtcatggctc tttctaagaa gtaggtggtt tacaagaatg cattttgtca 46980 tctgcatatc tatttccgag gcagtataat ttagtagtta agagctggaa tcttagaagc 47040 aaagtggaat tacatttgtg gctccatcac ttacttgtgg tgatcctagg cctctctgag 47100 tcataatttt ctcatctgta aacctgggac agtaatacct actgtaggtg actactctag 47160 gaattgaatg agataatatc ccaaaaacac ccagcacaga gctggcacgt ggtacatgct 47220 cagttggctc ttgttgcaaa gacagtactt cagtggccta gttacaaaac actctgagga 47280 gtgacagttt tgttctgtcg actggagcct tccctgatga ctctaaggag actagtcatc 47340 attttaagga atctgccttc agtatcttgt gttttgataa acgtacagca catggaattg 47400 ctagacagac tggaatctaa cttttggggt acatgtttgc aaagataact aagaaatcag 47460 caaattctgg gtaatttaag aaataagtgt actagaatct tcatataaat gtgtctgtcc 47520 gggaaagtgt gccattgtga tgaggatgtt tctgaaacaa tctcatcctt tgtctttgta 47580 gtgaaacggg agacattaga accatggttt tcccagtgat gtacctcaat gaggtaagtc 47640 ctgagacgga gggagccacg ggtgttttca gactcagaaa aaatccatta tgatgtctac 47700 tgttgtagtt acatgtaagt tatgacagaa gggcaaaaga tttttaaaac ctgttattcc 47760 tcagaaaatt tcacttaaat gttcacatga atctgcctgt gtctgagagc tgatttggag 47820 aaatgatgga aagaaatttt ccttctcaag aacactattt gggcaaaact cccttctggg 47880 gagctgctca cgtaggaaac agaaacaggt aaaaggagcc attggcagac attgttgaag 47940 cagggaaata gctcacactc agatagatgc cagctagccc tttgtctccc ccttctttga 48000 aaccatgctg gtttaagaca cctatgataa attcttttct gaatcacata tcacgtttac 48060 tgtagttata tctcctcagt ttctcctgct tccgcccagt ttgagggaaa aaaaaaaaac 48120 gcaggttttt ttcttcaata aattcttgat tggcaaactt ctccttttta ttatttttgt 48180 gtttcctaaa aatacttgct gtttgtagaa tattgaataa cagagattag caagaaaaag 48240 aaaaattaaa atcactattc acaaaatctg tgtcagcctg ataatatttt tattttattt 48300 tactcaatgt gttgtacaat tttttccaat aacaacttta aaaggtaatc taatgtttta 48360 cattttataa aacatgtgct ctttataaaa ttcttagaaa tttttttaaa aattgattta 48420 aaaagtaaat tactgataag tccctctcta tcagaggcag gtgcagttca gatgtcaact 48480 cctgatattt tctggtcttg atattacata gttgaaatca tacgatagat acaattttat 48540 atcttttttc tccatttagc attatattgg tattcacatt tacaaacttt taagggtttg 48600 ttattacaat tctaagatga ggtttttatc gtttcatagg aaaaattcaa gcaatattta 48660 ccaatttata ggatctcttt gcaattgctc ctgatcatcc atgttcctgt ttgtgggcag 48720 gggcatgaaa gatctttttg aaaatgcaga agggcccttt tctgccaact tctgttcagt 48780 agtggcatat ttgaagtccc tccaccccca acttctaatt tgcttttttg tgaaagacta 48840 gattaagtcc aggtgtgtgg agtggaacct tgtatttttg ctgcctccta ggaagagcgt 48900 gattattctc ttctctagaa aaataaaata ttagacctgg aagtctggaa gtgacattgg 48960 agactgttgc cacaccacct ttttaccgag gaggaaactc tatccagtta ttggaaaaaa 49020 tgtcttagaa cccaatccac tgactcggtc caatgaaaaa aaatgctttc ttttcttttt 49080 tttttttttt tgagacaagg tctcactctc accctctaca gtggtgcgat tttggctcac 49140 tgcagcctcg acttcccggg ctcaagtgat cctcccacct ctgccttcca agtagctgga 49200 actacaggtg tgtgccacca tgcccggcta attttttttt tttttcctga gatggagtct 49260 tgctctgttg cccaggctgg agtgcagtgg cccaatctca gctcacggca acctctgcct 49320 cctgggttca agcaattctc gtgcctcggc ctcccaagta gctgggacta caggcgcccg 49380 ccaccacccc tggctaattt ttgtattttt agcagagatg aggtttcacc atgttgaaac 49440 tcatgacctc aagtgatctg cccatctcgg cctcccaaag tgctgggatt acagtcatga 49500 gccaccatgc ccagccccag ctaatttttg tattttttgt agagaggtgg tttcaccaca 49560 ttgctcaggc tggtctcaaa cttttgagct caagcaatcc gcctgccttg gcctcccaaa 49620 gtgctgggat tataggcgtg tgcaactatg ccaggcctcc agtgcaaatt aagcctaaac 49680 taggccagaa ttgttgctca ttatttctat ggaattaagc tcttcagata cctcactcat 49740 tacactaggt ggtaattcct ctgctctgca tacactaagt gttattctag tacatttcct 49800 tctatcagca gtctctggaa ttctagttag cccacaactt tgctgagcac tttctgtaga 49860 gggctgtggt cctgattact atagatgtaa ccaagaaaga aattatactt tccacatacc 49920 atttttgcag tgtttcattt atttattcat ttaatcagcc agcattaatc aagcacctac 49980 tgtgtgctgg gtgctatacc cagtgtggag gtgactgagg ttaagtcttg ccttcaggga 50040 cttcacagcc attgcaagac aaacagttac aatgcagagt gcaaggacaa tgatggaagt 50100 agagagtgag atggaaactt agggaggagg cctttgacta ggcctgaggt agccagagaa 50160 aacttttgga aggaagtgat gctgagctgg atttttaagg atgaattgga attatctgac 50220 ataaaacaaa aggtgatact gtctcaatat ttctgaatac attttacctc ctttttccaa 50280 tctattttaa gagtaaaaaa aatgtcttca ggagaagaca agatattaat gaataaatgt 50340 cccttctgat tactctgact tataaatgga ttttcagtat gtttggtttg ctaacaggag 50400 gacattccca aattgtatta aacaaaggaa agatatagca aaaaacagtt acacactgga 50460 tgtttagtca tcaagaatac tattttcttg cctctccaga gtgttcacat tgataaagag 50520 acggcgagtc gactgaagtc tatgattaac actactttga tcatcaccaa cataccctac 50580 atcatcatgg cgctgggtgt gttctttggt ttggttttta cctggcttgc atgcaaagga 50640 cagggatcca tggatgaggt gagaactggc tgaaggaact tcttccttac tggataactt 50700 tacctgagga attcaactgt acttcactga agggctgtca gctggcttat taggataaat 50760 tctgggattt tatgctgggc atagtgattt cgtgcttatt ttactgctgg accaaatggg 50820 aagcaaagga agtgtgtcaa agaaggtgga gggttagaag gtaccatcta atatttgggg 50880 aatagaatct ctttggatgt atcccctggg agttaacttt atgtctttga aaacaataac 50940 ctgaaagaaa aggaagaata tataacagtt acacatctga tctttggtgt cagactgcct 51000 gagttcaaat cccagttctg ccacttaaca gctatacgac cctagaaact gtgcttcagt 51060 ttcttcatct gtaaaatggg ataataaaag cctcccttat gagtttttca tgaggattag 51120 atgatatagt agacttaaag gacttggccc agtgttagca tatagtaaga gctcaataaa 51180 ggtttaagta ttattaaata tgataaaaca gctccaagat tatagagcaa gacagccagg 51240 gtcctgcttg gaaagaatcc ctgatgtatc cgaagatacc tatgatttag gtatcactgc 51300 ataataaatg attggaacat gggtgtagtt actttcctgg aaggctagga taaagagttg 51360 ggttcgcctt tccaagtgac cagcagccca gccaggaacc tgaatacctg caatgagcct 51420 tttctgtaga agcccttctt aaattttctg cagcttcctt ttttttacaa cagtggcctt 51480 ttttcctcca gtttcctcaa ctaagtgtcc aaggcaaatg tgaagtagaa aataaatacg 51540 tgaaaccatc tgagtaaaat tagctgaatt tccctgactt ccatattctt ccattatttc 51600 tcttatcccc tgccagtcac tttagcctga attagctgtg aggcaaacta ttttgccatt 51660 tctatgtgtg gatcttccag tgtgacttta tgcagtcatt gaaattgtct taagcacaaa 51720 tgaaacctca tggaaatgtt aattactgct cctacaatta accttcctca tatattcaac 51780 aagcaaggaa ttattgagaa ctaatacctc tgagacacta ctccttagta ggtttcaaac 51840 caggaaggag gcaagttgaa tagagtctaa gttttataat ccagatcaac acagagaagg 51900 gtactgctct ggtattgagg gtgggagtgg tcagagaagg cctcctggaa aggttaggcc 51960 tgctgaatct tcaagaacaa gcagcagccc aagaggggag gtgagtgaga tgagccacct 52020 tcctataggt ctctcctcct tccatgcccc cactccccac ccaaactttt cacactgggg 52080 agaagtttct gacatgaaca tctaacttgt tttctctctt ctgtgtttca gggaacagcg 52140 gatgaaagag cacccctcat tcgaacctaa acattgcctt tgcttggtga agaaactgtg 52200 tgagctgtcc tgacctggac gatgacgtgg ggaaaccctc cacctccttg caggcttgtt 52260 gcctgttgaa agaaggaaaa agacacggcg ctggcaagtg ataggaacat tctggccaga 52320 ggttaaagag caggctgaca tggctggcca ttaagcttta taaaatcatg tgggctctga 52380 aattgttctt ttatgtgtct agcaagtatt taataaaccc ttgtatagta attttgttgt 52440 tgttgggtgc tggtagctcc agaattttgt gaccactatt gtgggtaaaa tgtctctgca 52500 tcacttgtta atgctactgg tctaacttca ttcagtatgc ttcattcacc gaactttgtg 52560 ctcaaaatgc gtatatacca ttttatgttg tattcctcca tttcacttgc aaaacagaag 52620 taaataagag ttcgggaccc agggtaaaat ggtagcttca tccaatatat cattcaaatg 52680 catctgattt ctaaaacata ttacatttta tgctgatctt cagttcataa ttcttccagg 52740 aaaactcagt cttccaactg caataaaata ctgggtagaa tcaaatggga aaggggttgg 52800 gtggggcaat acccatgagt tgatagtgat aagctcctaa ggatttttaa cttgtacttt 52860 tgtgaacgaa gagaatgcat aaataatgtt ggtgaggata aagtacagat atttcatgta 52920 gaattaattg ctagttatga tgcttgtgga tagttaactg tttttttttt agtcaaaatg 52980 atcatgctac gaaaagatgc ttctgagaga atgtaatgag taactgattt ttcttcctga 53040 gtcgcccttg ccaaatatgt tactgtatta attaatctaa tattgagtga ttatttgtaa 53100 aattatgaat atgggaaatc catctatcta cagcctaagt tacacataag tttcagaaag 53160 tctgattaga ctaaagagat atttcttctg ggacagccgc cttcttggta attttgaagt 53220 tctttttaca agttccttcc tcagtttcag ttctttccag tgttttgtag ctcactgtca 53280 ctcactgaat agagaaacgt gtgccctata cttcctgtga caatcatttt gctgacagaa 53340 tgatggatgt ttaaaatatt gcacaaagta ctttaaagaa aggtctgtta ggaccagaag 53400 cagagacacc acttttcaaa ggacttcttg gtttcagcat aacctaagac agggaattgg 53460 gagccatcat atgtcacagt gttcagaatt caagcatatt taagggcatt ttctttgatt 53520 ctcaaagttc agcattcatt ttgaattgag aagcctatac atttagctga caaagtgctt 53580 atagaatttc ttaacaactg aaccattcaa aaggattttt tttgtttaaa actggatttc 53640 aatgtaagca aatgaagaaa aaaatataga tttcatttcc atagcttctt atccctgtat 53700 tgaggtaata aattgtttta ctgacaattt ttcctttttc tacactaaaa caatatgtga 53760 tatatttccc ctcttgaaga ggcaattcat taaactctca aattttctat agaatcaaga 53820 tagaaccttt agatactcca actcaccaaa atgtaaaaaa actaacaaaa atatttggtc 53880 ttcaataatg ctaaatatct acatttttag aatttatcaa catttaacta gataattggg 53940 catgtcttaa ttatgcatgt acttatccat actaataaaa ttgacaatgc tagtgcatac 54000 ttattggttt agtcctatta tcaggatata atcatctgtg aggaggatat tttaaatact 54060 gtaaatgata acagttaatg atatacacat ttagactgag ttgcacactg gcagggagac 54120 caaaaacatt acttccatac ttgtgtcatg attctttttt ttttgagaga gtctcactct 54180 gtcgccaggc tggagtacag tggcatgatc tcggctcact gcaacctctg cctcccgggt 54240 tcaagcaatt ctcctgcctc agccacccaa gtagctggga ctacaggtgc gtgccaccac 54300 gcccagctaa attttgtatt tttagtggag acggggtttc accatgttgg ccaggatggt 54360 ctcaatctcc tgaccctgcg atctgcccac ctcagcctcc caaagtgctg ggattacagg 54420 cgtaagccac cgggcctggc ctgttttatg attcttaata gttacttggt ttaaatcaca 54480 tttgatacta tccttctgaa aagtctgaga cagatctaca aactacagtc aaaattatag 54540 attaagagga atgaatgcac ctatttggct ttaagttgaa gatgaattat ttctcatgct 54600 cattttcttg cggcagttat cttagaaaga cccccaaagg ctttgtgatt gtaagcactg 54660 tcatgatcac agaatgcaag cttctggtac catgatcctc aacttagaga ggaagaaacc 54720 aagacagaga gcttaactca cttctctcag ggaaaattag gagttgagca caggacagga 54780 aatgggcttt gccactttta gctccaggct tttctaacca gacttgattt cctcatgttc 54840 tagaaagatc actaatggtc aagtggaaca agcactacac gactaacccc tattggggtt 54900 tttaacttaa gggaggctaa tttttaattt aaactgctcg agatatgagt tctgcaaaag 54960 gtggtccgca tccttggccc tctggacatt atcactaaat tgcttgtgcc tgttaacaag 55020 aatactgacc agaatgctct tcatgtagct tatacagttg gttcacttca tgcggttctt 55080 gacatgttta tttctaccct taatgcaatg aaatgtttca ttaataaaaa accactttat 55140 at 55142 29 4748 DNA Homo sapiens 29 cctcgcgggg ttgcggcgag cccggcccgc gaacgtcacg tccctgcgcg ctccctgcac 60 tctcccgagc tgcgctaggc gggcgccacg gctgcccggc gaaggaaacc gaaaccgagt 120 ccgggcccgt ccctccgcgg ccccatccgc ccggtgcacc cggggccgcg ctcgccaggc 180 cgcggagccc agagctgcgc gcacgaaccg tgcgccggga gggcgtgggc gtggcgccga 240 agggtcccgg gtcttcgacg cctctgcggc ggctcctccc tccttgcagt tggatccctg 300 gcgggtgcgg cccggcccgg cccgtgagcg gcgcacagaa tgggccgatg ctgcttctac 360 acggcgggga cgttgtccct gctcctgctg gtgaccagcg tcacgctgct ggtggcccgg 420 gtcttccaga aggctgtaga ccagagtatc gagaagaaaa ttgtgttaag gaatggtact 480 gaggcatttg actcctggga gaagccccct ctgcctgtgt atactcagtt ctatttcttc 540 aatgtcacca atccagagga gatcctcaga ggggagaccc ctcgggtgga agaagtgggg 600 ccatacacct acagggaact cagaaacaaa gcaaatattc aatttggaga taatggaaca 660 acaatatctg ctgttagcaa caaggcctat gtttttgaac gagaccaatc tgttggagac 720 cctaaaattg acttaattag aacattaaat attcctgtat tgactgtcat agagtggtcc 780 caggtgcact tcctcaggga gatcatcgag gccatgttga aagcctatca gcagaagctc 840 tttgtgactc acacagttga cgaattgctc tggggctaca aagatgaaat cttgtccctt 900 atccatgttt tcaggcccga tatctctccc tattttggcc tattctatga gaaaaatggg 960 actaatgatg gagactatgt ttttctaact ggagaagaca gttaccttaa ctttacaaaa 1020 attgtggaat ggaatgggaa aacgtcactt gactggtgga taacagacaa gtgcaatatg 1080 attaatggaa cagatggaga ttcttttcac ccactaataa ccaaagatga ggtcctttat 1140 gtcttcccat ctgacttttg caggtcagtg tatattactt tcagtgacta tgagagtgta 1200 cagggactgc ctgcctttcg gtataaagtt cctgcagaaa tattagccaa tacgtcagac 1260 aatgccggct tctgtatacc tgagggaaac tgcctgggct caggagttct gaatgtcagc 1320 atctgcaaga atggtgcacc catcattatg tctttcccac acttttacca agcagatgag 1380 aggtttgttt ctgccataga aggcatgcac ccaaatcagg aagaccatga gacatttgtg 1440 gacattaatc ctttgactgg aataatccta aaagcagcca agaggttcca aatcaacatt 1500 tatgtcaaaa aattagatga ctttgttgaa acgggagaca ttagaaccat ggttttccca 1560 gtgatgtacc tcaatgagag tgttcacatt gataaagaga cggcgagtcg actgaagtct 1620 atgattaaca ctactttgat catcaccaac ataccctaca tcatcatggc gctgggtgtg 1680 ttctttggtt tggtttttac ctggcttgca tgcaaaggac agggatccat ggatgaggga 1740 acagcggatg aaagagcacc cctcattcga acctaaacat tgcctttgct tggtgaagaa 1800 actgtgtgag ctgtcctgac ctggacgatg acgtggggaa accctccacc tccttgcagg 1860 cttgttgcct gttgaaagaa ggaaaaagac acggcgctgg caagtgatag gaacattctg 1920 gccagaggtt aaagagcagg ctgacatggc tggccattaa gctttataaa atcatgtggg 1980 ctctgaaatt gttcttttat gtgtctagca agtatttaat aaacccttgt atagtaattt 2040 tgttgttgtt gggtgctggt agctccagaa ttttgtgacc actattgtgg gtaaaatgtc 2100 tctgcatcac ttgttaatgc tactggtcta acttcattca gtatgcttca ttcaccgaac 2160 tttgtgctca aaatgcgtat ataccatttt atgttgtatt cctccatttc acttgcaaaa 2220 cagaagtaaa taagagttcg ggacccaggg taaaatggta gcttcatcca atatatcatt 2280 caaatgcatc tgatttctaa aacatattac attttatgct gatcttcagt tcataattct 2340 tccaggaaaa ctcagtcttc caactgcaat aaaatactgg gtagaatcaa atgggaaagg 2400 ggttgggtgg ggcaataccc atgagttgat agtgataagc tcctaaggat ttttaacttg 2460 tacttttgtg aacgaagaga atgcataaat aatgttggtg aggataaagt acagatattt 2520 catgtagaat taattgctag ttatgatgct tgtggatagt taactgtttt ttttttagtc 2580 aaaatgatca tgctacgaaa agatgcttct gagagaatgt aatgagtaac tgatttttct 2640 tcctgagtcg cccttgccaa atatgttact gtattaatta atctaatatt gagtgattat 2700 ttgtaaaatt atgaatatgg gaaatccatc tatctacagc ctaagttaca cataagtttc 2760 agaaagtctg attagactaa agagatattt cttctgggac agccgccttc ttggtaattt 2820 tgaagttctt tttacaagtt ccttcctcag tttcagttct ttccagtgtt ttgtagctca 2880 ctgtcactca ctgaatagag aaacgtgtgc cctatacttc ctgtgacaat cattttgctg 2940 acagaatgat ggatgtttaa aatattgcac aaagtacttt aaagaaaggt ctgttaggac 3000 cagaagcaga gacaccactt ttcaaaggac ttcttggttt cagcataacc taagacaggg 3060 aattgggagc catcatatgt cacagtgttc agaattcaag catatttaag ggcattttct 3120 ttgattctca aagttcagca ttcattttga attgagaagc ctatacattt agctgacaaa 3180 gtgcttatag aatttcttaa caactgaacc attcaaaagg attttttttg tttaaaactg 3240 gatttcaatg taagcaaatg aagaaaaaaa tatagatttc atttccatag cttcttatcc 3300 ctgtattgag gtaataaatt gttttactga caatttttcc tttttctaca ctaaaacaat 3360 atgtgatata tttcccctct tgaagaggca attcattaaa ctctcaaatt ttctatagaa 3420 tcaagataga acctttagat actccaactc accaaaatgt aaaaaaacta acaaaaatat 3480 ttggtcttca ataatgctaa atatctacat ttttagaatt tatcaacatt taactagata 3540 attgggcatg tcttaattat gcatgtactt atccatacta ataaaattga caatgctagt 3600 gcatacttat tggtttagtc ctattatcag gatataatca tctgtgagga ggatatttta 3660 aatactgtaa atgataacag ttaatgatat acacatttag actgagttgc acactggcag 3720 ggagaccaaa aacattactt ccatacttgt gtcatgattc tttttttttt gagagagtct 3780 cactctgtcg ccaggctgga gtacagtggc atgatctcgg ctcactgcaa cctctgcctc 3840 ccgggttcaa gcaattctcc tgcctcagcc acccaagtag ctgggactac aggtgcgtgc 3900 caccacgccc agctaaattt tgtattttta gtggagacgg ggtttcacca tgttggccag 3960 gatggtctca atctcctgac cctgcgatct gcccacctca gcctcccaaa gtgctgggat 4020 tacaggcgta agccaccggg cctggcctgt tttatgattc ttaatagtta cttggtttaa 4080 atcacatttg atactatcct tctgaaaagt ctgagacaga tctacaaact acagtcaaaa 4140 ttatagatta agaggaatga atgcacctat ttggctttaa gttgaagatg aattatttct 4200 catgctcatt ttcttgcggc agttatctta gaaagacccc caaaggcttt gtgattgtaa 4260 gcactgtcat gatcacagaa tgcaagcttc tggtaccatg atcctcaact tagagaggaa 4320 gaaaccaaga cagagagctt aactcacttc tctcagggaa aattaggagt tgagcacagg 4380 acaggaaatg ggctttgcca cttttagctc caggcttttc taaccagact tgatttcctc 4440 atgttctaga aagatcacta atggtcaagt ggaacaagca ctacacgact aacccctatt 4500 ggggttttta acttaaggga ggctaatttt taatttaaac tgctcgagat atgagttctg 4560 caaaaggtgg tccgcatcct tggccctctg gacattatca ctaaattgct tgtgcctgtt 4620 aacaagaata ctgaccagaa tgctcttcat gtagcttata cagttggttc acttcatgcg 4680 gttcttgaca tgtttatttc tacccttaat gcaatgaaat gtttcattaa taaaaaacca 4740 ctttatat 4748 30 478 PRT Homo sapiens 30 Met Gly Arg Cys Cys Phe Tyr Thr Ala Gly Thr Leu Ser Leu Leu Leu 1 5 10 15 Leu Val Thr Ser Val Thr Leu Leu Val Ala Arg Val Phe Gln Lys Ala 20 25 30 Val Asp Gln Ser Ile Glu Lys Lys Ile Val Leu Arg Asn Gly Thr Glu 35 40 45 Ala Phe Asp Ser Trp Glu Lys Pro Pro Leu Pro Val Tyr Thr Gln Phe 50 55 60 Tyr Phe Phe Asn Val Thr Asn Pro Glu Glu Ile Leu Arg Gly Glu Thr 65 70 75 80 Pro Arg Val Glu Glu Val Gly Pro Tyr Thr Tyr Arg Glu Leu Arg Asn 85 90 95 Lys Ala Asn Ile Gln Phe Gly Asp Asn Gly Thr Thr Ile Ser Ala Val 100 105 110 Ser Asn Lys Ala Tyr Val Phe Glu Arg Asp Gln Ser Val Gly Asp Pro 115 120 125 Lys Ile Asp Leu Ile Arg Thr Leu Asn Ile Pro Val Leu Thr Val Ile 130 135 140 Glu Trp Ser Gln Val His Phe Leu Arg Glu Ile Ile Glu Ala Met Leu 145 150 155 160 Lys Ala Tyr Gln Gln Lys Leu Phe Val Thr His Thr Val Asp Glu Leu 165 170 175 Leu Trp Gly Tyr Lys Asp Glu Ile Leu Ser Leu Ile His Val Phe Arg 180 185 190 Pro Asp Ile Ser Pro Tyr Phe Gly Leu Phe Tyr Glu Lys Asn Gly Thr 195 200 205 Asn Asp Gly Asp Tyr Val Phe Leu Thr Gly Glu Asp Ser Tyr Leu Asn 210 215 220 Phe Thr Lys Ile Val Glu Trp Asn Gly Lys Thr Ser Leu Asp Trp Trp 225 230 235 240 Ile Thr Asp Lys Cys Asn Met Ile Asn Gly Thr Asp Gly Asp Ser Phe 245 250 255 His Pro Leu Ile Thr Lys Asp Glu Val Leu Tyr Val Phe Pro Ser Asp 260 265 270 Phe Cys Arg Ser Val Tyr Ile Thr Phe Ser Asp Tyr Glu Ser Val Gln 275 280 285 Gly Leu Pro Ala Phe Arg Tyr Lys Val Pro Ala Glu Ile Leu Ala Asn 290 295 300 Thr Ser Asp Asn Ala Gly Phe Cys Ile Pro Glu Gly Asn Cys Leu Gly 305 310 315 320 Ser Gly Val Leu Asn Val Ser Ile Cys Lys Asn Gly Ala Pro Ile Ile 325 330 335 Met Ser Phe Pro His Phe Tyr Gln Ala Asp Glu Arg Phe Val Ser Ala 340 345 350 Ile Glu Gly Met His Pro Asn Gln Glu Asp His Glu Thr Phe Val Asp 355 360 365 Ile Asn Pro Leu Thr Gly Ile Ile Leu Lys Ala Ala Lys Arg Phe Gln 370 375 380 Ile Asn Ile Tyr Val Lys Lys Leu Asp Asp Phe Val Glu Thr Gly Asp 385 390 395 400 Ile Arg Thr Met Val Phe Pro Val Met Tyr Leu Asn Glu Ser Val His 405 410 415 Ile Asp Lys Glu Thr Ala Ser Arg Leu Lys Ser Met Ile Asn Thr Thr 420 425 430 Leu Ile Ile Thr Asn Ile Pro Tyr Ile Ile Met Ala Leu Gly Val Phe 435 440 445 Phe Gly Leu Val Phe Thr Trp Leu Ala Cys Lys Gly Gln Gly Ser Met 450 455 460 Asp Glu Gly Thr Ala Asp Glu Arg Ala Pro Leu Ile Arg Thr 465 470 475 US 20120270245 A1 20121025 US 13425928 20120321 13 DE 102006053442.5 20061112 20060101 A
G
01 N 33 566 F I 20121025 US B H
20060101 A
C
12 M 1 40 L I 20121025 US B H
US 435 792 436501 4352872 422 69 DIAGNOSIS AND RISK STRATIFICATION OF INFECTIONS AND CHRONIC DISEASES OF THE RESPIRATORY TRACT AND LUNGS BY MEANS OF PROVASOPRESSIN, PARTICULARLY COPEPTIN OR NEUROPHYSIN II US 12514524 20090922 US 8158368 WO PCT/DE07/02037 20071111 US 13425928 Bergmann Andreas
Berlin DE
omitted DE
Morgenthaler Nils
Berlin DE
omitted DE
Papassotiriou Jana
Berlin DE
omitted DE
Struck Joachim
Berlin DE
omitted DE
Müller Beat
Basel CH
omitted CH
BRAHMS GmbH 03
Henningsdorf DE

The invention relates to a method for diagnosing and/or stratifying the risk of infections or chronic diseases of the respiratory tract and lungs, particularly lower respiratory tract infections and chronic obstructive pulmonary disease. In said method, provasopressin (proAVP) or fragments or partial peptides thereof, especially copeptin or neurophysin II, is/are determined. The invention further relates to suitable biomarker combinations for in-vitro diagnosis.

embedded image
embedded image
embedded image
embedded image
SPECIFICATION

The invention relates to a method for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs, particularly of lower respiratory tract infections (LRTI) and COPD (chronic obstructive pulmonary disease), where a determination of provasopressin (proAVP) or fragments and partial peptides thereof, particularly copeptin or neurophysin II, is carried out. Furthermore, the invention relates to a combination of biomarkers for in vitro diagnosis, suitable for this purpose.

For the purpose of suitable therapy, an early diagnosis and differentiation of the infections or chronic diseases of the airways and lungs is/are already required in the emergency room, in connection with the need to make clinical decisions. Because of the non-specific symptoms (difficulty breathing) in the case of infections or chronic diseases of the airways and lungs, both differentiation and a distinction from other diseases, and recognition of the concrete infection or chronic disease of the airways and lungs, are essential.

Copeptin (also: C-terminal proAVP) is described in WO 2006/018315 (BRAHMS AG) as a biomarker for in vitro diagnosis of heart disease and related pulmonary dysfunctions (“pulmonary disorders”). A copeptin assay related to this is disclosed in Morgenthaler et al. (Nils G. Morgenthaler, Joachim Struck, Christine Alonso and Andreas Bergmann, Assay for the Measurement of Copeptin, a Stable Peptide Derived from the Precursor of Vasopressin, Clinical Chemistry 52: 112-119, 2006).

In the state of the art, the procalcitonin (PCT) determination is described for the purpose of a study to distinguish bacterial sepsis (threshold value >0.5 ng/mL) from other disease causes (EP0656121). PCT is also described in the literature in connection with pneumonias, where the studies are primarily related, with regard to a diagnosis, to discriminating between different pathogen types in the case of pneumonia that has already been diagnosed (Prat C, Dominguez J, Andreo F, Blanco S, Pallares A, Cuchillo F, Ramil C, Ruiz-Manzano J, Ausina V, Procalcitonin and neopterin correlation with aetiology and severity of pneumonia, J Infect. 52(3) (2006): pp 169-177 and Masia M, Gutierrez F, Shum C, Padilla S, Navarro JC, Flores E, Hernandez I, Masia M, Gutierrez F, Shum C, Padilla S, Navarro JC, Flores E, Hernandez I {sic—repetition of names in original}, Chest 128(4) (2005): pp 2223-2239, Boussekey N, Leroy O, Georges H, Devos P, d'Escrivan T, Guery B, Diagnostic and prognostic values of admission procalcitonin levels in community-acquired pneumonia in an intensive care unit. Infection 33(4) (2005): pp 257-63). In a study by Zhou et al (Zhou CD et al Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2006 Jun, 18(6), 370-2), PCT is presented as a diagnostic marker for early diagnosis of ventilator-associated pneumonia in an intensive care unit. PCT is also described as a diagnostic marker in pneumonias (Prat et al. 2006 (supra) and Masia M et al. 2005 (supra), Boussekey N et al. 2005 (supra), Christ-Crain M, Morgenthaler NG, Solz D, Muller C, Bingisser R, Harbarth S, Tamm M, Struck J, Bergmann A, Muller B, Pro-adrenomedullin to predict severity and outcome in community-acquired pneumonia, Crit Care 10(3) (2006): pp R96). Furthermore, there are studies in which it was shown that clinically relevant infections (including bacterial pneumonias) that require antibiotic therapy are detected in patients who are suspected of having infections of the lower airways (including pneumonia), using PCT, at a threshold concentration of >0.1 ng/mL and >0.25 ng/mL, respectively (Christ-Crain M, Stolz D, Bingisser R, Muller C, Miedinger D, Huber PR, Zimmerli W, Harbarth S, Tamm M, Muller B, Procalcitonin Guidance of Antibiotic Therapy in Community-acquired Pneumonia: A Randomized Trial, Am J Respir Crit Care Med 174(1) (2006), pp. 84-93 and Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Muller B, Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomized, single-blinded intervention trial, Lancet 21;363(9409) (2004): pp 600-607, Stolz D, Christ-Crain M, Gencay MM, Bingisser R, Huber PR, Muller B, Tamm M, Diagnostic value of signs, symptoms and laboratory values in lower respiratory tract infection, Swiss Med Wkly 8;136(27-28) (2006): pp 434-440).

However, a marker combination of copeptin and procalcitonin is not described.

Certain clinical studies concerning COPD are known (Soler-Cataluna JJ, Martinez-Garcia MA, Roman Sanchez P, et al. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 1005; 60:925-931; Antonelli Incalzi R, Fuso L, De Rosa M, et al. Co-morbidity contributes to predict mortality of patients with chronic obstructive pulmonary disease. Eur Respir J 1997; 10:2794-2800; Yohannes AM, Baldwin RC, Connolly MJ. Predictors of 1-year mortality in patients discharged from hospital following acute exacerbation of chronic obstructive pulmonary disease. Age Ageing 2005; 34:491-496; Almagro P, Barreiro B, Ochoa de Echaguen A, et al. Risk factors for hospital readmission in patients with chronic obstructive pulmonary disease. Respiration 2006; 73:311-317).

However, it is a disadvantage of known diagnosis methods using previously known markers that early and complete detection of risk patients is not successful, and therefore risk stratification takes place only to an insufficient degree. One task that underlies the invention therefore consists in developing a method for risk stratification for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs, which allows an improved detection of at-risk patients. {sic—first occurrence of “for risk stratification in preceding sentence appears to be superfluous}

It is furthermore disadvantageous that in the state of the art, sufficient sensitivity and/or specificity of the markers is generally not achieved.

Another task therefore consists in making available a method for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs, where at least one marker or a combination of markers demonstrates sufficient sensitivity and specificity.

It is therefore the task of the present invention to make available a method for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs.

This task is accomplished by means of a method for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs, where a determination of provasopressin (proAVP) or fragments and partial peptides thereof, particularly copeptin or neurophysin II, is carried out (hereinafter: method according to the invention).

Surprisingly, provasopressins (proAVPs) or fragments and partial peptides thereof, preferably copeptin or neurophysin II, demonstrate great sensitivity and specificity for the diagnosis of infections or chronic diseases of the airways and lungs.

Within the scope of this invention, the term “infections of the airways and lungs” is particularly understood to mean those infections that are caused by bacteria, viruses, fungi, or parasites, for example those indications such as lower respiratory tract infections (LRTI), bronchitis, pneumonia, sarcoidosis, bronchiectases, non-cardiac pulmonary edema.

Furthermore, lower respiratory tract infections (LRTI), bronchitis, putrid bronchitis, pneumonia are particularly preferred, according to the invention. Pneumonia, particularly community associated pneumonia (CAP), and lower respiratory tract infections (LRTI) are very particularly preferred.

Within the scope of this invention, pneumonia is understood to mean an acute or chronic disease of the lung tissue, and its infection is caused by bacteria, viruses or fungi, parasites, rarely also toxically by means of inhalation of toxic substances, or immunologically. For the clinician, pneumonia is a constellation of various symptoms (fever or hypothermia, shivers, cough, pleuritic thorax pain, increased sputum production, increased respiratory rate, dull percussion sound, bronchial breathing, crepitation close to the ear, pleural rubbing) in combination with at least one infiltrate that can be seen on the thorax X-ray (Harrisons Innere Medizin {Harrison's Internal Medicine}, published by Manfred Dietel, Norbert Suttorp and Martin Zeitz, ABW Wissenschaftsverlag 2005).

Within the scope of this invention, “chronic diseases of the lungs and airways” are understood to be those indications such as interstitial lung diseases and lung fibroses, chronic obstructive pulmonary diseases (COPD), particularly COPD infection exacerbations, bronchial asthma, particularly infection exacerbations in cases of bronchial asthma, bronchial carcinoma. COPD, particularly COPD infection exacerbations, is/are particularly preferred.

According to the invention, COPD refers to a group of chronic diseases that are characterized by coughing, increased sputum, and difficulty breathing when under stress. Chronic-obstructive bronchitis and pulmonary emphysema should primarily be mentioned. Both disease profiles are characterized in that exhalation (expiration) is particularly hindered. A colloquial term for the main symptom of COPD is also “smoker's cough.” The invention is particularly advantageous in cases of acute exacerbations.

According to the invention, the term “risk stratification” comprises finding those patients, particularly emergency patients and at-risk patients, who have a poorer prognosis, for the purpose of more intensive diagnosis and therapy/treatment of infections or chronic diseases of the airways and lungs, with the goal of allowing the most advantageous possible course. Risk stratification according to the invention therefore allows an effective treatment method, which are possible in the case of infections or chronic diseases of the airways and lungs, using medications, particularly antibiotics. {sic—singular direct object in first part of sentence, plural verb in relative clause relating to this direct object}

For this reason, the invention also relates to identification of patients having an increased risk and/or a disadvantageous prognosis of infections or chronic diseases of the airways and lungs, specifically in the case of symptomatic and/or asymptomatic patients, particularly emergency patients.

In the case of emergency and/or intensive-care medicine, in particular, reliable stratification can take place by means of the method according to the invention, in particularly advantageous manner. The method according to the invention therefore allows clinical decisions that lead to rapid therapy success and to the avoidance of deaths. Such a clinical decision, according to the invention, also comprises hospitalization of the patients.

For this reason, the invention also relates to a method for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs, for the purpose of making clinical decisions, such as further treatment and therapy by means of medications, particularly antibiotics, preferably in the time-critical situation of intensive-care medicine or emergency medicine.

In another preferred embodiment, the method according to the invention therefore relates to therapy control of an infection or chronic disease of the airways and lungs.

In another preferred embodiment of the method according to the invention, the diagnosis and/or risk stratification takes place for prognosis, for early recognition and recognition by means of a differential diagnosis, for an assessment of the degree of severity, and for an assessment of the progression over the course of therapy.

In another preferred embodiment, the invention relates to a method for in vitro diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs, where a determination of the marker provasopressin (proAVP) or fragments and partial peptides thereof, particularly copeptin or neurophysin II, is carried out on a patient to be examined. However, copeptin or a fragment or partial sequence thereof is particularly preferred. In particular, copeptin demonstrates an advantageously great stability in the serum and plasma, for purposes of in vitro diagnosis (Morgenthaler NG, Struck J, Alonso C., et al. Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin, Clin Chem 2006; 52:112-119).

Furthermore, the invention relates a method for diagnosis and/or risk stratification of infections and chronic diseases of the airways and lungs, or to a method for in vitro diagnosis for early or differential diagnosis or prognosis of infections or chronic diseases of the airways and lungs, according to one of the above embodiments, where after occurrence of the symptoms, a cut-off (threshold value) range of 6-20 pmol/L of the marker provasopressin (proAVP) or fragments and partial peptides thereof, particularly copeptin or neurophysin II, is significant (specific) for diagnosis and/or risk stratification. Furthermore, a cut-off (threshold value) of 6-10 pmol/L, particularly 9 pmol/L, is preferred, preferably 2 hours after occurrence of the symptoms.

Furthermore, the invention relates to a method for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs, or to a method for early or differential diagnosis or prognosis of infections or chronic diseases of the airways and lungs, according to one of the above embodiments, where after occurrence of the symptoms, a cut-off (threshold value) of 10-50 pmol/L of the marker provasopressin (proAVP) or fragments and partial peptides thereof, particularly copeptin or neurophysin H, is significant (specific) for prognosis and/or risk stratification. Furthermore, a cut-off (threshold value) of 10-40 pmol/L is preferred.

On this basis, these methods according to the invention are advantageously sensitive.

In an embodiment of the method according to the invention, bodily fluid, particularly blood, is taken from the patient to be examined, optionally whole blood or serum or obtainable plasma, and the diagnosis takes place in vitro/ex vivo, i.e. outside of the human or animal body. On the basis of the determination of the marker provasopressin (proAVP) or fragments and partial peptides thereof, particularly copeptin and neurophysin II, great sensitivity and specificity for infections or chronic diseases of the airways and lungs are achieved, and the diagnosis or risk stratification can take place using the amount that is present in at least one patient sample. However, the marker copeptin (stable fragment of proAVP or pre-provasopressin) or a fragment or partial sequence thereof is particularly preferred.

Within the scope of this invention, “provasopressin” is understood to be a human protein or polypeptide that can be obtained from pre-provasopressin, and comprises the amino acids 29-164 within the scope of pre-provasopressin (see also WO2006/018315 and FIG. 1), and fragments or partial peptides that can be obtained from it, particularly copeptin (fragment: amino acids 126-164 (39 amino acids: SEQ: ASDRSNATQL DGPAGALLLR LVQLAGAPEP FEPAQPDAY) or neurophysin II (fragment: amino acids 32-124 of pre-provasopressin (93 amino acids: SEQ: AMSDLELRQC LPCGPGGKGR CFGPSICCAD ELGCFVGTAE ALRCQEENYL PSPCQSGQKA CGSGGRCAAF GVCCNDESCV TEPECREGFH RRA). Furthermore, these polypeptides according to the invention can demonstrate post-translational modifications, such as glycolization, lip(o)idization, or derivativization.

In another embodiment, the determination of provasopressin (proAVP) or fragments and partial peptides thereof, particularly copeptin or neurophysin II, can additionally take place with further markers, specifically preferably those that already indicate infections or chronic diseases of the airways and lungs.

For this reason, the invention relates to an embodiment of the method according to the invention where the determination is additionally carried out with at least one further marker selected from the group of inflammatory markers, in a patient to be examined.

According to the invention, the inflammatory marker can be selected from at least one marker of the group of C-reactive protein (CRP), cytokines, such as TNF-alpha, for example, interleukins, such as IL-6, for example, procalcitonin (1-116, 3-116), and adhesion molecules, such as VCAM or ICAM.

In a particularly preferred embodiment, the invention relates to a particularly advantageous combination of biomarkers, specifically provasopressin (proAVP) or fragments and partial peptides thereof, particularly copeptin or neurophysin II, with procalcitonin (1-116, 3-116) and/or the group of C-reactive protein (CRP).

For this reason, the invention relates to a method for in vitro diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs, where a determination of the marker provasopressin (proAVP) or fragments and partial peptides thereof, particularly copeptin or neurophysin II, is carried out, in combination with procalcitonin (1-116, 3-116) or a partial sequence thereof, in each instance, in a patient to be examined. Again, a combination of neurophysin II, copeptin and procalcitonin is particularly preferred, particularly copeptin and procalcitonin. These stated biomarker combinations demonstrate synergies, in particularly advantageous manner, which lead to improved specificity and sensitivity for diagnosis of the {word/words missing}.

Within the scope of this invention, “procalcitonin” is understood to be a human protein or polypeptide having an amino acid sequence of 1-116 amino acids or 2-116 amino acids (PCT 2-116) or 3-116 amino acids (PCT 3-116), as described in EP0656121, EP1121600 of the applicant, as well as DE10027954A1. Furthermore, the procalcitonin according to the invention can demonstrate post-translational modifications, such as glycolization, lip(o)idization, or derivativization. Furthermore, partial sequences or fragments of procalcitonin are also included.

In another embodiment of the invention, the method according to the invention can be carried out within the scope of an in vitro diagnosis, by means of parallel or simultaneous determination of the markers (e.g. multi-titer plates with 96 cavities and more), where the determinations are carried out on at least one patient sample.

Furthermore, the method according to the invention and its determinations can be carried out using an automated analysis device, particularly using a Kryptor (http://www.kryptor.net/).

In another embodiment, the method according to the invention and its determinations can be carried out by means of a rapid test (e.g. lateral flow test), whether using single-parameter or multi-parameter determinations. In a particularly preferred embodiment, this is a self-test or a device that is suitable for use in emergency diagnosis.

Furthermore, the invention relates to the use of provasopressin (proAVP) or fragments and partial peptides thereof, particularly copeptin or neurophysin II, for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs, and/or for in vitro diagnosis for early or differential diagnosis or prognosis of infections or chronic diseases of the airways and lungs.

In a particular embodiment, the invention relates to the use of provasopressin (proAVP) or fragments and partial peptides thereof, particularly copeptin or neurophysin II, in combination with procalcitonin (1-116, 3-116) or a partial sequence thereof, in each instance, for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs.

Use according to the invention can take place with at least one other suitable marker, if necessary (called “panel” or “cluster”).

Another task is making available a corresponding diagnostic device for carrying out the method according to the invention.

Within the scope of this invention, such a diagnostic device is particularly understood to be an array or assay (e.g. immune assay, ELISA, etc.), in the broadest sense a device for carrying out the method according to the invention.

The invention furthermore relates to a kit for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs, containing detection reagents for determining the provasopressin (proAVP) or fragments and partial peptides thereof, particularly copeptin or neurophysin II, and possibly additional markers mentioned above. Such detection reagents comprise antibodies, etc., for example.

The following examples and figures serve for a more detailed explanation of the invention, but without restricting the invention to these examples and figures.

EXAMPLES AND FIGURES Example 1

Blood samples were taken of patients who came to the emergency room of a hospital with the leading symptom of respiratory distress, during the initial examination.

Number of test subjects: 167

Sample-Taking, Biomarker Analysis:

Blood samples were taken by means of standard serum Monovettes. After a coagulation period of 20-40 min, centrifugation was carried out for 15 min at 2000 g; subsequent serum separation was carried out by means of decanting. The serum samples were stored at −20 degrees C. until further use.

Copeptin assay according to Morgenthaler et al (Morgenthaler NG, Struck J, Alonso C, et al. Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin, Clin Chem 2006; 52:112-119).

Detection limit: 1.7 pmol/L.

COPD in the Case of Acute Worsening (Event):

It was possible to determine that copeptin, CRP, and procalcitonin were significantly increased after 14 days or 6 months.

Copeptin values of 167 patients (age (mean) 70 years) were studied. The patients came to the emergency room with acute exacerbation of an existing COPD. The patients were examined clinically with regard to their pulmonary function, at admission, after 14 days, and after 6 months. Table 1 shows an overview of the clinical parameters of the patients upon admission to the emergency room.

TABLE 1 Clinical parameters at admission of 167 patients with acute exacerbation of a COPD Parameter n = 167 Sex (M/F) (%) 75/92 (44.9/55.1) Age in years (from to) 70 (42-91) Smoking packages/year 45 (30-60) {Translator's Note: The German word used, Packungen, translates literally to packages - unclear whether packs or cartons are meant} Average duration of COPD months (SD) 127 (86) Duration of exacerbation in days 4 (3-7) Cough (%) 142 (85) Increased sputum production (%) 113 (67.7) Discolored sputum (%) 95 (56.9) Difficulty breathing (%) 155 (92.8) Fever (%) 68 (40.7) Comorbidity (%) Cardiopathy 76 (45.5) Tumor 24 (14.4) Diabetes mellitus 19 (11.4) Severity of COPD - GOLD stage (%) I 10 (6.0) II 35 (21.0) III 74 (44.3) IV 48 (28.7) FEV1 in liters (SD) 0.892 (0.397) FEV1% expected (%) 39.9 (16.9) PaO2 mmHg 62.9 (15.7) PaCO2 mmHg 43.8 (11.0) Leukocytes × 109/l (SD) 11.27 (4.7)

In a multi-variant analysis (p=0.006, Cox Regression Analysis), the measured copeptin value was a predictor for a poor clinical progression, independent of age, existing comorbidity, hypoxemia, and restricted pulmonary function. It was only possible to achieve successful long-term therapy in 44 percent of the patients who had copeptin values ≧40 pmol/L upon admission. In contrast to this, it was possible to achieve success in 82 percent of the patients who had copeptin values <40 pmol/L (p<0.0001).

From this, it becomes evident that copeptin represents a prognosis marker for a disadvantageous clinical progression in the case of patients with COPE (and other pulmonary diseases). Copeptin could identify those patients who need particularly intensive therapy for their existing pulmonary diseases, at an early point in time.

Table 2 and FIGS. 2 and 3 explain the situation in detail.

TABLE 2 Comparison of the clinical result of patients with copeptin levels <40 pmol/L and ≧40 pmol/L upon admission Copeptin < Copeptin ≧ 40 pmol/L 40 pmol/L n = 140 n = 27 p value Hospitalization period 26.4% (37) 3.7% (1) 0.010 <24 hours % (n) Period of 8.5 (1-15) 14 (8-18) 0.002 hospitalization Days (IQR) Need for intensive- 6.4% (9) 25.9% (7) 0.002 care unit % (n) Period of intensive- 2 (1.5-4.5) 5 (3-5) 0.097 care unit (IQR) Hospitalization 0.17 ± 0.4 0.55 ± 0.74 0.005 rate within 6 months Average time to 163 ± 45 111 ± 73  <<0.001 clinical failure Long-term clinical 17.9% (25) 55.6% (15) <<0.001 failure % (n) Death during 1.4% (2) 11.1% (3) 0.007 hospitalization % (n) Death within 6 months 5% (7) 25.9% (7) <<0.001 % (n)

FIGURES

FIG. 1 shows the amino acid sequence of pre-provasopressin.

FIG. 2 shows the relationship between stays in the hospital of patients with CAP/pneumonia and the measured copeptin plasma value upon admission. This is shown as a probability of hospital discharge over time. Patients with copeptin values <40 pmol/L upon admission had a significantly shorter hospital stay in comparison with patients with copeptin values >40 pmol/L.

Number of patients on the days indicated (d):

Copeptin <40 pmol/L:

n=140 (0 d) 88 (5 d) 54 (10 d) 28 (15 d) 12 (20 d) 1 (25 d) 1 (30 d) 0 (35 d)

Copeptin≧40 pmol/L:

n=27 (0 d) 23 (5 d) 18 (10 d) 12 (15 d) 5 (20 d) 4 (25 d) 1 (30 d) 0 (35 d)

FIG. 3 shows the relationship between the frequency of complications (death, repeat hospitalization after discharge) and the copeptin plasma value upon admission. This is shown as the time free of event (freedom of event). Event is defined as death or repeat hospitalization after initial discharge. Patients with copeptin values <40 pmol/L upon admission had this event significantly less frequently than patients with copeptin values >40 pmol/L. Number of patients on the days indicated (d):

Copeptin<40 pmol/L:

n=140 (0 d) 133 (30 d) 129 (60 d) 126 (90 d) 123 (120 d) 120 (150 d) 115 (180 d)

Copeptin>40 pmol/L:

n=27 (0 d) 21 (30 d) 16 (60 d) 16 (90 d) 15 (120 d) 13 (150 d) 12 (180 d)

1. Method for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs, comprising determining provasopressin (proAVP) or fragments and partial peptides thereof. 2. Method for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs according to claim 1, for identifying patients having an increased risk and/or a disadvantageous prognosis of infections or chronic diseases of the airways and lungs. 3. Method for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs according to claim 1, where the patient is a symptomatic and/or asymptomatic patient, particularly an emergency patient. 4. Method for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs according to claim 1, for carrying out clinical decisions, particularly further treatment and therapy by means of medications, particularly antibiotics, particularly in intensive-care medicine or emergency medicine, and for hospitalization of the patient. 5. Method for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs according to claim 1, further comprising determining procalcitonin and/or the group of C-reactive protein (CRP), or a partial sequence thereof, in each instance, in a patient to be examined. 6. Method for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs according to claim 1, characterized in that the diagnosis takes place for prophylaxis, for prognosis, for early recognition and recognition by means of a differential diagnosis, for an assessment of the degree of severity, and for an assessment of the progression over the course of therapy. 7. Method according to claim 1, characterized in that the cut-off (threshold value) for diagnosis, 6-20 pmol/L, or the cut-off (threshold value) for prognosis, 10-50 pmol/L, of the marker provasopressin (proAVP) or fragments and partial peptides thereof, is significant (specific). 8. Method according to claim 1, further comprising determining at least one other marker selected from the group consisting of inflammatory markers. 9. Method according to claim 8, characterized in that the inflammatory marker is at least one marker selected from the group consisting of cytokines, interleukins, and adhesion molecules. 10. Method according to claim 1, characterized in that parallel or simultaneous determinations of the markers are carried out. 11. Method according to claim 1, characterized in that the determinations are carried out using at least one patient sample. 12. Method according to claim 1, characterized in that the determinations are carried out using an automated analysis device. 13. Method according to claim 1, characterized in that the determinations are carried out by means of a rapid test. 14. Method according to claim 1, characterized in that the risk stratification takes place for prognosis, for early recognition and recognition by means of a differential diagnosis, for an assessment of the degree of severity, and for an assessment of the progression over the course of therapy, of acute coronary syndrome. 15. (canceled) 16. (canceled) 17. Kit for diagnosis and/or risk stratification of infections or chronic diseases of the airways and lungs, comprising detection reagents for determining provasopressin (proAVP) or fragments and partial peptides thereof, and optionally other markers according to claim 8, and ancillary substances. 18. Diagnostic device for carrying out a method according to claim 1. 19. The method of claim 1, wherein the fragment of proAVP is copeptin or neurophysin II.


Download full PDF for full patent description/claims.

Advertise on FreshPatents.com - Rates & Info


You can also Monitor Keywords and Search for tracking patents relating to this Diagnosis and risk stratification of infections and chronic diseases of the respiratory tract and lungs by means of provasopressin, particularly copeptin or neurophysin ii patent application.
###
monitor keywords

Browse recent Brahms Gmbh patents

Keyword Monitor How KEYWORD MONITOR works... a FREE service from FreshPatents
1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored.
3. Each week you receive an email with patent applications related to your keywords.  
Start now! - Receive info on patent apps like Diagnosis and risk stratification of infections and chronic diseases of the respiratory tract and lungs by means of provasopressin, particularly copeptin or neurophysin ii or other areas of interest.
###


Previous Patent Application:
Diagnosing and managing venous thromboembolism and intracardiac thrombi using a provoked d-dimer test
Next Patent Application:
Means and methods for diagnosing and/or treating a subject at risk of developing heart failure
Industry Class:
Chemistry: molecular biology and microbiology
Thank you for viewing the Diagnosis and risk stratification of infections and chronic diseases of the respiratory tract and lungs by means of provasopressin, particularly copeptin or neurophysin ii patent info.
- - -

Results in 0.37744 seconds


Other interesting Freshpatents.com categories:
Amazon , Microsoft , Boeing , IBM , Facebook

###

Data source: patent applications published in the public domain by the United States Patent and Trademark Office (USPTO). Information published here is for research/educational purposes only. FreshPatents is not affiliated with the USPTO, assignee companies, inventors, law firms or other assignees. Patent applications, documents and images may contain trademarks of the respective companies/authors. FreshPatents is not responsible for the accuracy, validity or otherwise contents of these public document patent application filings. When possible a complete PDF is provided, however, in some cases the presented document/images is an abstract or sampling of the full patent application for display purposes. FreshPatents.com Terms/Support
-g2-0.2865
     SHARE
  
           

stats Patent Info
Application #
US 20120270245 A1
Publish Date
10/25/2012
Document #
File Date
01/31/2015
USPTO Class
Other USPTO Classes
International Class
/
Drawings
0


Your Message Here(14K)


Lungs
Respiratory Tract
Respiratory Tract Infections


Follow us on Twitter
twitter icon@FreshPatents

Brahms Gmbh

Browse recent Brahms Gmbh patents

Chemistry: Molecular Biology And Microbiology   Measuring Or Testing Process Involving Enzymes Or Micro-organisms; Composition Or Test Strip Therefore; Processes Of Forming Such Composition Or Test Strip   Involving Antigen-antibody Binding, Specific Binding Protein Assay Or Specific Ligand-receptor Binding Assay   Assay In Which An Enzyme Present Is A Label   Heterogeneous Or Solid Phase Assay System (e.g., Elisa, Etc.)