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Glucocorticoid control of gene transcription in neural tissue Morsink, M.C.

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(1)Glucocorticoid control of gene transcription in neural tissue Morsink, M.C.. Citation Morsink, M. C. (2007, June 26). Glucocorticoid control of gene transcription in neural tissue. Retrieved from https://hdl.handle.net/1887/12094 Version:. Corrected Publisher’s Version. License:. Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden. Downloaded from:. https://hdl.handle.net/1887/12094. Note: To cite this publication please use the final published version (if applicable)..

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(15) SD@""@BU. $ZUPTLFMFUPO. "#FYPOT@T@BU. "'@T@BU. 6@H@BU. +@J@BU. . . . . .  . . 6653@T@BU. . 9@BU. .@BU. . SD@""@BU. "'@BU. . . SD@"*@T@BU. SD@"*@H@BU. . "'@BU. . . '$IPVST. . . . '$IPVS. SD@""@BU. 6@BU. %@BU. %@BU. 9@BU. &DET@T@BU. 1SPCF4FU*%. . . '$IPVST. TZOEFDBOCJOEJOHQSPUFJO. NFUIJPOJOFBEFOPTZMUSBOTGFSBTF**. DZUPTPMJDNBMBUFEFIZESPHFOBTF .EI . TNPPUINVTDMFTQFDJmDCFUBIZESPYZTUFSPJE EFIZESPHFOBTF. BMLBMJOFQIPTQIBUBTF UJTTVFOPOTQFDJm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

(16) . . .@BU . . 9@BU. SD@""@BU. . "'@BU. . . 9N3/"@T@BU. SD@""@BU. . . . TPMVUFDBSSJFSGBNJMZNFNCFS. USBOTQPSUPYZHFOUSBOTQPSU. USBOTQPSUPYZHFOUSBOTQPSU. USBOTQPSUOFVSPUSBOTNJUUFSUSBOTQPSU. USBOTQPSUNJUPDIPOESJBMUSBOTQPSU. USBOTQPSUJOUSBDFMMVMBSQSPUFJOUSBOTQPSU. VCJRVJUJODZDMFQSPUFJONPEJm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mMJO. (FOF5JUMF. %@T@BU. . '$IPVST. "#@BU. 5SBOTQPSUNJTDFMMBOFPVT. . . %@BU. 6@BU. . %@BU. . . 6@BU. . '$IPVST. &DET@BU. . . '$IPVS. "#@T@BU. 6CJRVJUJOQBUIXBZ. .@T@BU. SD@""@BU. 1SPCF4FU*%. $IBQUFS.

(17) .  . SD@"*@H@BU. . 9FYPO@H@BU. %@T@BU. 4ZOBQUJDUSBOTNJTTJPO. . "#@BU. -@BU.  . 4@BU. "#@BU. . . .@H@BU. $FMMBEIFTJPO. . . SD@""@T@BU. . '$IPVST. 6@BU. . '$IPVST. SD@"*@BU. .@BU. . . 9N3/"@T@BU. 9DET@T@BU. . '$IPVS. 9N3/"@T@BU. *POUSBOTQPSU. 1SPCF4FU*%. DBUJPOUSBOTQPSU. DBMDJVNJPOUSBOTQPSUDBUJPOUSBOTQPSU. DIMPSJEFUSBOTQPSUSFHVMBUJPOPGDFMMWPMVNF. TPEJVNJPOUSBOTQPSUHFOFSBUJPOPGBDUJPO QPUFOUJBM. . QPUBTTJVNJPOUSBOTQPSUUSBOTQPSUJPOUSBOTQPSU. QPUBTTJVNJPOUSBOTQPSUUSBOTQPSUJPOUSBOTQPSU. (0#JPMPHJDBM1SPDFTT%FTDSJQUJPO. CSJEHJOHJOUFHSBUPS. QSFQSPOPDJDFQUJO. NPOPBNJOFPYJEBTF". OFVSFYJO. BDUJWBUFEMFVLPDZUFDFMMBEIFTJPONPMFDVMF. TZOEFDBO. BUZQJDBM1,$TQFDJmDCJOEJOHQSPUFJO. . $IBQUFS. TZOBQUJDUSBOTNJTTJPOFOEPDZUPTJTDFMM EJõFSFOUJBUJPO. TZOBQUJDUSBOTNJTTJPOOFVSPQFQUJEFTJHOBMJOH QBUIXBZ. OFVSPUSBOTNJUUFSDBUBCPMJTNFMFDUSPOUSBOTQPSU. DFMMBEIFTJPO. DFMMBEIFTJPOTJHOBMUSBOTEVDUJPO. DFMMBEIFTJPODFMMDFMMTJHOBMJOH. DFMMDFMMBEIFTJPODZUPLJOFTJTDFMMDZDMF. "51BTF )

(18) USBOTQPSUJOH MZTPTPNBM7TVCVOJUBJTPGPSN QSPUPOUSBOTQPSU . "51BTF DMBTT** UZQF". "51BTF $B

(19)

(20) USBOTQPSUJOH QMBTNBNFNCSBOF. DIMPSJEFDIBOOFM OVDMFPUJEFTFOTJUJWF ". TPEJVNDIBOOFM WPMUBHFHBUFE UZQF BMQIB QPMZQFQUJEF. QPUBTTJVNWPMUBHFHBUFEDIBOOFM TIBLFSSFMBUFE  NFNCFS. QPUBTTJVNWPMUBHFHBUFEDIBOOFM 4IBXSFMBUFE  NFNCFS. QPUBTTJVNWPMUBHFHBUFEDIBOOFM 4IBXSFMBUFE  NFNCFS. (FOF5JUMF. $IBQUFS.

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nBNNBUPSZSFTQPOTFIFUFSPQIJMJDDFMMBEIFTJPO. JNNVOFSFTQPOTFJSPOJPOUSBOTQPSUJSPOJPO IPNFPTUBTJT. JNNVOFSFTQPOTF. JNNVOFSFTQPOTF. (4USBOTJUJPOPGNJUPUJDDFMMDZDMFDBMDJVNJPO USBOTQPSU. SFHVMBUJPOPGDFMMDZDMF(4USBOTJUJPOPGNJUPUJD DFMMDZDMF. OFHBUJWFSFHVMBUJPOPGDFMMQSPMJGFSBUJPODFMM QSPMJGFSBUJPO. SFHVMBUJPOPGDFMMQSPMJGFSBUJPO. OFVSPUSBOTNJUUFSTFDSFUJPOUSBOTQPSU. TZOBQUJDUSBOTNJTTJPO DIPMJOFSHJD. (0#JPMPHJDBM1SPDFTT%FTDSJQUJPO. $IBQUFS.

(22)  . +@BU. 6@BU. . '$IPVST. &-07-GBNJMZNFNCFS. FYQSFTTFEJOOPONFUBTUBUJDDFMMT. EFMFUFEJONBMJHOBOUCSBJOUVNPST. NZPTJOMJHIUDIBJOLJOBTF TLFMFUBMNVTDMF. QSPUFJOUZSPTJOFQIPTQIBUBTF OPOSFDFQUPSUZQF. NZFMPJEBTTPDJBUFEEJõFSFOUJBUJPONBSLFS. QBSWBMCVNJO. OFVSPOBUJOBMQIB. QSPUFJOCFUBTVCUZQF. QSPUFJOUZSPTJOFQIPTQIBUBTF OPOSFDFQUPSUZQF. BOOFYJO". )IJTUPOFGBNJMZ NFNCFS. $ZTUFJOFTUSJOHQSPUFJO. IFBUTIPDLL%BQSPUFJO. IFBUTIPDLL%BQSPUFJO. (FOF5JUMF. GBUUZBDJEFMPOHBUJPO. (51CJPTZOUIFTJT651CJPTZOUIFTJT$51 CJPTZOUIFTJT. SFTQPOTFUPXPVOEJOHDFMMEJõFSFOUJBUJPO UJTTVFSFHFOFSBUJPO. QSPUFJOBNJOPBDJEQIPTQIPSZMBUJPO. QSPUFJOBNJOPBDJEEFQIPTQIPSZMBUJPO. NZFMPJECMPPEDFMMEJõ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mSTU(0DPNQPOFOU4JODFUIJTJTBOBSCJUSBSZEJWJTJPO NBOZHFOFTDBOCFQMBDFEJOUPNVMUJQMF GVODUJPOBMDBUFHPSJFT. SD@""@BU. . . SD@"*@T@BU. . . SD@""@BU. .@T@BU. . SD@"*@BU. SD@"*@BU. . . 4@BU. . . %FYPO@T@BU. . '$IPVST. 6@BU. . . '$IPVS. SD@"*@BU. .JTDFMMBOFPVT. SD@""@BU. SD@"*@BU. SD@"*@H@BU. 1SPUFJOGPMEJOH. 1SPCF4FU*%. $IBQUFS. .

(23) $IBQUFS. GR-activation by a brief corticosterone pulse. 1 hour. 3 hours. overlap. 0 genes  81 genes  FDR 43 %. 2 4. 5 hours. overlap. 61 genes  100 genes  FDR 37 %. 2. 15 genes  0 genes  FDR 53 %. 'JHVSF%JõFSFOUXBWFTPGHFOFFYQSFTTJPOBGUFSHMVDPDPSUJDPJESFDFQUPS (3 BDUJWBUJPOBDDPSEJOHUPBQBUUFSOPGFYDMVTJWFMZEPXOSFHVMBUFE HFOFTIPVSBGUFS(3BDUJWBUJPO CPUIVQPSEPXOSFHVMBUFEHFOFTIPVSTBGUFS(3BDUJWBUJPOBOEVQSFHVMBUFEHFOFTIPVSTBGUFS (3BDUJWBUJPO5IFBSSPXTJOEJDBUFPWFSMBQCFUXFFOUIFUJNFQPJOUT5IFVTFSEFmOFE'BMTF%JTDPWFSZ3BUF '%3 GSPN4JHOJmDBODF"OBMZTJTPG .JDSPBSSBZT 4". BOBMZTJTJTJOEJDBUFE. CBDL UP CBTFMJOF  XJUI POMZ  HFOFT CFJOH VQSFHVMBUFE 'VSUIFSNPSF  UIFSF XBT WFSZ MJUUMFPWFSMBQCFUXFFOUIFUJNFQPJOUT 5BCMF &YDFQUGPSGPVSHFOFTBUUIFIPVSTUJNF QPJOU BMMUIFPUIFSSFTQPOTJWFHFOFTBUFBDIUJNFQPJOUHFOFSBUFESFMJBCMFTJHOBMTPOUIF "õZNFUSJY(FOF$IJQTBUUIFPUIFSUJNFQPJOUT UIFSFCZFMJNJOBUJOHUIFQPTTJCJMJUZUIBU UIFTFHFOFTXFSFOPUQJDLFEVQBTSFTQPOTJWFHFOFTJOUIFPUIFSUJNFQPJOUTEVFUPMBDL PGTJHOBMPOUIF"õZNFUSJY(FOF$IJQT *O PSEFS UP EFUFSNJOF XIFUIFS DIBOHJOH UIF VTFSEFmOFE '%3 XPVME JOnVFODF UIF PCTFSWFEQBUUFSO UIF'%3TXFSFJODSFBTFEUPUIFIJHIFTUQPTTJCMFWBMVFT5IJTEJEOPU BMUFSUIFPCTFSWFEQBUUFSOPG FYDMVTJWFEPXOSFHVMBUJPOPGHFOFTIPVSBGUFS(3BDUJ WBUJPO  CPUIVQBOEEPXOSFHVMBUFEHFOFTIPVSTBGUFS(3BDUJWBUJPOBOE UIFTNBMM PWFSMBQCFUXFFOUIFUJNFQPJOUT)PXFWFS JODSFBTJOHUIF'%3GPSUIFIPVSTUJNFQPJOU SFTVMUFEJOUIFBEEJUJPOPGEPXOSFHVMBUFEHFOFTUPUIFMJTUPGSFTQPOTJWFHFOFT. (3SFTQPOTJWFHFOFTGVODUJPOBMDMBTTJmDBUJPO *OPSEFSUPBTTJHOGVODUJPOTUPUIFSFTQPOTJWFUSBOTDSJQUT (FOF0OUPMPHZDMBTTJmDBUJPOT XFSFPCUBJOFEVTJOHUIF/FU"õY"OBMZTJT$FOUFS(FOFTXFSFHSPVQFEUPHFUIFSJOUPB MBSHF WBSJFUZ PG GVODUJPOBM DMBTTFT "DUJWBUJPO PG (3 DMFBSMZ BõFDUFE UIF FYQSFTTJPO PG HFOFT JOWPMWFE JO EJõFSFOU UZQFT PG DFMMVMBS NFUBCPMJTN  USBOTDSJQUJPO  USBOTMBUJPO  EJG GFSFOUBTQFDUTPGTJHOBMUSBOTEVDUJPO QSPUFJOWFTJDMFUSBöDLJOH JPOUSBOTQPSU DFMMBEIF TJPO UIFDZUPTLFMFUPOBOETZOBQUJDUSBOTNJTTJPO)FODF JOHFOFSBM UIFEJõFSFOUXBWFT PGHFOFFYQSFTTJPOBUEJõFSFOUUJNFQPJOUTDPOUBJOFETJNJMBSGVODUJPOBMHFOFHSPVQT. .

(24) $IBQUFS. 5BCMF0WFSMBQQJOHHFOFTCFUXFFOUIFUISFFUJNFQPJOUT'$GPMEDIBOHF (FOFUJUMF. '$ IPVS. '$ IPVST. "'@T@BU. OFSWFHSPXUIGBDUPSJOEVDFEGBDUPS". . . '$ IPVST. 9DET@T@BU. IZCSJEQSPUFJO VCJRVJUJOMJLFQSPUFJOSQT. . . 6653@T@BU. EFWFMPQNFOUBMMZSFHVMBUFEDBSEJBDGBDUPS %3$' . . . SD@""@H@BU. &453O. . . %@T@BU. NPOPBNJOFPYJEBTF". . . .@BU. CFUBDIBJODMBUISJOBTTPDJBUFEQSPUFJODPNQMFY"1. . . . SD@""@BU. &453O. . . $IBQUFS. 1SPCFTFU*%. (FOFTUIBUPWFSMBQCFUXFFOUIFUISFFUJNFQPJOUT'SPNMFGUUPSJHIUBSFMJTUFEUIF(FOF$IJQ1SPCF4FU*%T UIFHFOFUJUMFTBOEUIFGPMEDIBOHFTJO UIF BOEIPVSTUJNFQPJOU. 4PNFPGUIFJOUFSFTUJOHSFTQPOTJWFHFOFTXFSFDMBTTJmFEBTTJHOBMUSBOTEVDUJPODPNQP OFOUTBOEJODMVEFEDPSUJDPUSPQJOSFMFBTJOHIPSNPOF $3) SFDFQUPS NJUPHFOBDUJWBUFE QSPUFJO LJOBTF LJOBTF   -*., BOE DBMNPEVMJO  "EEJUJPOBMMZ  HFOFT GSPN PUIFS GVOD UJPOBMHSPVQTTVDIBTBOJB 3/"QSPDFTTJOH NPOPBNJOFPYJEBTF" OFVSPUSBOTNJUUFS DBUBCPMJTN UXPQPUBTTJVNJPODIBOOFMTBOEQSFQSPOPDJDFQUJO TZOBQUJDUSBOTNJTTJPO  XFSFBMTPJEFOUJmFEBTIJQQPDBNQBM(3SFTQPOTJWFHFOFT. 0WFSMBQXJUIUIF4"(&EBUBTFU 8F QSFWJPVTMZ VTFE BESFOBMFDUPNZ JO DPNCJOBUJPO XJUI MPX DPSUJDPTUFSPOF QFMMFUT .3PDDVQBUJPO  BOE IJHI DPSUJDPTUFSPOF JOKFDUJPOT JO WJWP (3 PDDVQBUJPO  UP BTTFTT DPSUJDPTUFSPJESFHVMBUFEHFOFFYQSFTTJPOJOSBUIJQQPDBNQVTIPVSTBGUFSBIJHIDPS UJDPTUFSPOFJOKFDUJPO VTJOH4FSJBM"OBMZTJTPG(FOF&YQSFTTJPO  #SJFnZ JO4"(& HFOF FYQSFTTJPOQSPmMFTBSFFTUBCMJTIFECZTFRVFODJOHBOEDPVOUJOHCBTFQBJSTMPOH4"(& UBHTXIJDIBSFEFSJWFEGSPNBEFmOFEQPTJUJPOXJUIJOUIFVOUSBOTMBUFESFHJPOTPGUIF USBOTDSJQUT  *OPSEFSUPDPNQBSFUIFDVSSFOUEBUBTFUXJUIUIF4"(&EBUBTFU XFVTFE CPUIUIF&YQSFTTJPO"OBMZTJT4ZTUFNBUJD&YQMPSFS &"4& BOEUIF/$#*4"(&NBQGUQTJUF BTEFTDSJCFEJOUIFNBUFSJBMTBOENFUIPETTFDUJPO 'JHVSF 4JODF OPUFWFSZ4"(&UBH BOE"õZNFUSJYQSPCFTFUDPVMECFBOOPUBUFEXJUIB6OJ(FOFDMVTUFSBOE OPUFWFSZ BOOPUBUFE4"(&UBHXBTQSFTFOUPOUIF"õZNFUSJY(FOF$IJQ POMZTFWFOUZPGUIF SFTQPOTJWF4"(&UBHTDPVMECFBOOPUBUFEBT"õZNFUSJYQSPCFTFUT)PXFWFS TUJMM   PGUIFSFTQPOTJWFHFOFTGPVOEXJUI4"(&XFSFBMTPSFHVMBUFEIPVSBGUFS(3BDUJWBUJPO JOUIJTTUVEZ XIFSFBTHFOFT  XFSFSFHVMBUFEIPVSTBGUFS(3BDUJWBUJPO 5BCMF  5IFNBKPSJUZPGUIFTFHFOFTTIPXFEUIFTBNFEJSFDUJPOPGSFHVMBUJPO HFOFTPVUPG  QSPWJEJOHHPPEQPTJUJWFDPOUSPMTGPSUIFDVSSFOUEBUBTFU5XPPGUIFTFHFOFT NBMBUF EFIZESPHFOBTFBOE'"51BTFBMQIBTVCVOJU QMBZBSPMFJODFMMVMBSNFUBCPMJTNXIFSFBT BOPUIFS  BQPMJQPQSPUFJO &  GVODUJPOT BT B MJQJE USBOTQPSUFS BOE JT JOWPMWFE JO TZOBQUJD. .

(25) $IBQUFS. Affymetrix probe sets. SAGE tags. UniGene clusters EASE. NCBI SAGEmap. 70 responsive SAGE tags annotated as Affymetrix probe sets 'JHVSF$SPTTQMBUGPSNDPNQBSJTPOCFUXFFO4FSJBM"OBMZTJTPG(FOF&YQSFTTJPO 4"(& UBHTBOE"õZNFUSJYQSPCFTFUT"õZNFUSJYQSPCFTFUT XFSFBOOPUBUFEXJUI6OJ(FOFDMVTUFSTVTJOH&YQSFTTJPO"OBMZTJT4ZTUFNBUJD&YQMPSFS &"4& XIFSFBT4"(&UBHTXFSFBOOPUBUFEVTJOHUIF/$#* 4"(&NBQ#PUIBOOPUBUJPOUPPMTQSPWJEFJOGPSNBUJPOPOUIF6OJ(FOFCVJMETVTFEJOUIFBOOPUBUJPOQSPDFTTBOEUIFSFGPSFBMMPXDPNQBSJTPOPG EBUBTFUTWJBUIFTBNFCVJMET CVJME  5BCMF0WFSMBQXJUI4"(&'$GPMEDIBOHF 4"(&UBH. 6OJHFOFT. 1SPCFTFU*%. (FOFUJUMF. '$ IPVS. 4"(& DIBOHF. (""$"5"555. 3O. 9@BU. EZOFJO DZUPQMBTNJD JOUFSNFEJBUFDIBJO. . (3EPXO. 5((5((""5(. 3O. -@BU. DBTFJOLJOBTF** BMQIBQPMZQFQUJEF. . .3EPXO. 5"5""5$5(5. 3O. .@BU. NBUSJO. . (3VQ. "$55"(55(5. 3O. 9@BU. "51TZOUIBTFDPVQMJOHGBDUPS. . .3VQ. 4"(&UBH. 6OJHFOFT. 1SPCFTFU*%. (FOFUJUMF. '$ IPVST. 4"(& DIBOHF. 555(5("$5(. 3O. "'@BU. #'"EFQFOEFOU"%1SJCPTZMBUJPOTVCTUSBUF  #"34. .3VQ. "$(5"""""". 3O. "'@T@BU. DZUPTPMJDNBMBUFEFIZESPHFOBTF .EI . . .3VQ. ("("($5""$. 3O. 6@BU. OFVSPOBUJOBMQIB. . .3VQ. "$$"($$"((. 3O. 9@BU. BQPMJQPQSPUFJO&. . (3VQ. (5(((5(5(5. 3O. SD@""@S@BU. &453O. . (3EPXO. ""5""""(55. 3O. 9@BU. '"51BTFBMQIBTVCVOJU. . (3EPXO. 55($5(55(". 3O. .@BU. DBMNPEVMJO. . .3EPXO. (FOFTUIBUPWFSMBQCFUXFFOUIFDVSSFOUBOEUIF4FSJBM"OBMZTJTPG(FOF&YQSFTTJPO 4"(& TUVEZ5IFVQQFSQBOFMEJTQMBZTUIFHFOFTUIBUPWFSMBQ CFUXFFOUIFIPVSUJNFQPJOUBOEUIF4"(&TUVEZUIFMPXFSQBOFMEJTQMBZTUIFHFOFTUIBUPWFSMBQCFUXFFOUIFIPVSTUJNFQPJOUBOEUIF 4"(&TUVEZ*OUIF4"(&DIBOHFDPMVNOHFOFTBSFSFTQPOTJWFUPUIFNJOFSBMPDPSUJDPJESFDFQUPSPSHMVDPDPSUJDPJESFDFQUPSBOEUIFEJSFDUJPOPG SFHVMBUJPOJTEFTJHOBUFEBTVQPSEPXO. .

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õZNFUSJY. '$ R1$3. 8JMDPYPO 7BMJEBUJPO. .JOFSBMPDPSUJDPJESFDFQUPS. TMJDFIPVS. . . 1. USVFQPTJUJWF. 4IBXSFMBUFEQPUBTTJVNDIBOOFM. TMJDFIPVS. . . 1. USVFQPTJUJWF. "UZQJDBM1,$TQFDJm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õZNFUSJY(FOF$IJQBOBMZTJTBOESFBMUJNFR1$3BSFEJTQMBZFEBTXFMMBTUIFSFTVMU PGTUBUJTUJDBMUFTUJOH 8JMDPYPO4JHOFE3BOLT5FTU (FOFTXFSFDMBTTJmFEBTUSVFQPTJUJWFTJGUIFFYQSFTTJPODIBOHFTPCTFSWFEXJUI"õZNFUSJY (FOF$IJQTDPVMECFSFQMJDBUFEXJUISFBMUJNFR1$3 . $IBQUFS. 7BMJEBUJPOPGBTVCTFUPGSFTQPOTJWFHFOFT.

(27) $IBQUFS LIMK1 (3 hours). EST 190379 (3 hours) 2.5. 0.8 0.7. 2. 0.5. expression. expression. 0.6. 0.4 0.3. 1.5. 1. 0.2. 0.5 0.1 0. 0. no cort. cort. no cort. treatment. cort treatment. Methallothionein (3 hours). Shaw-related potassium channel 2 ( 1 hour) 2.5 4.5 4. 2. 3. expression. expression. 3.5. 2.5 2 1.5 1. 1.5. 1. 0.5. 0.5. 0. 0. no cort. cort treatment. no cort. cort treatment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mSNFE 1 8JMDPYPO4JHOFE3BOLT5FTU. 5IF GPMEDIBOHFT PCUBJOFE CZ SFBMUJNF R1$3 XFSF JO HPPE DPODPSEBODF XJUI UIF GPMEDIBOHFT PCUBJOFE CZ (FOF$IJQ BOBMZTJT *OUFSFTUJOHMZ  EFTQJUF UIF SFMBUJWFMZ IJHI '%3TUIBUXFSFPCUBJOFECZBOBMZ[JOHUIF(FOF$IJQEBUBXJUI4". XFDPVMEDPOmSN (3SFTQPOTJWFOFTTPGPVUPGHFOFTCZSFBMUJNFR1$3. %*4$644*0/ 5IFBJNPGUIJTTUVEZXBTUPFMVDJEBUFQPUFOUJBMNPMFDVMBSNFDIBOJTNTVOEFSMZJOHUIF BDUJPO PG DPSUJDPTUFSPOF PO UIF IJQQPDBNQVT CZ HFOFSBUJOH B UJNF DVSWF PG QSFEPNJ OBOUMZ(3SFTQPOTJWFHFOFT8FJEFOUJmFEPWFSMJLFMZ(3SFTQPOTJWFHFOFTBOEGPVOE BDMFBSQBUUFSOPGNPEFSBUFDIBOHFTJOHFOFFYQSFTTJPOJOBMMUISFFUJNFQPJOUT. .

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