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Transformations which preserve exchangeability and application to permutation tests.

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(1)Transformations which preserve exchangeability and application to permutation tests. Daniel Commenges. To cite this version: Daniel Commenges. Transformations which preserve exchangeability and application to permutation tests.. Journal of Nonparametric Statistics, American Statistical Association, 2003, 15 (2), pp.171-185. �10.1080/1048525031000089310�. �inserm-00262035�. HAL Id: inserm-00262035 https://www.hal.inserm.fr/inserm-00262035 Submitted on 10 Mar 2008. HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés..

(2) HAL author manuscript Journal of Nonparametric Statistics 2003;15(2):171-185. HAL author manuscript. 

(3)   !#"$%'&()*+-,-.0/ 213,- 45 67!98:; <!=. inserm-00262035, version 1. @> ?#ABDCFEHGJILKMKNCOA5PLCFQ RJBSILQUTV?0TVBSQUTWBDXFQJYCF?#K[Z\2]^*_`a^ bLcdcLe Zf]g ^*>ihkjFl=monWp5C(q2CFr IN]?#BSPLA'?0TFh'RJILnUs5Ct?0pu!h;cLcLb=v#mh'w'nV?#A5XOC YCOE.x:yzc#c={}|N|#vM|#vj#j~eL€'w;?uy‚cLc={}|M|#mM0lMbLbdej ƒL?#A p'?0nU„ j#h;#bLbLc †*‡‰ˆ Š‹tŒf‹Ž@‘-Œf’”“•#‹t’—–-’”“‘–*˜t™Ž™=št›’—ˆiŠŒœ–– 7 ž!Ÿ‘ O¡O¢ £‰ ‰¤ ¥k¦=“f§ ‹Žˆ ¨Žœ‹t©’—ª—’«z¬N‡Ž­‡Ž©–-‘Œ®t‹t’«‡‰ˆ –:’—–$‹i¯Ž‘¬°“V‡‰ˆ± ’«’«‡‰ˆ²­D‡ŽŒ:‹tŠ Šª«¬L’—ˆ=¨~Š5‘Œf³=´ ‹t’«‡‰ˆM-œ––‘µ ¶2“f§ ‹tŒf‹Ž“V-‘ŒU’«·‘§ ª—’—ˆ œ‹tŒ -Œf‹Žˆ –-­D‡ŽŒf¸‹t’—‡‰ˆ – ¹*§’—“f§MŠ Œœ–-‘Œ®Ž:V¦0´ “f§ ‹Žˆ=¨Žœ‹t©’—ª—’«z¬Ž›L±’—–-’—ˆ=¨‰³’—–§ ’—ˆ ¨$–œ“V‡‰ˆ ±L´‚@‡‰@œˆ0ºV¦L“U§ ‹Žˆ=¨Žœ‹t©’”ª—’«‚¬~‹Žˆ ±7¨‰ª«‡Ž©‹ŽªV¦0´ “f§ ‹Žˆ=¨Žœ‹t©’—ª—’«z¬»0¹‹Žª—–-‡}V¦=‹Ž¸’—ˆ ºˆ ‡‰ˆL´‚ª—’—ˆ=œ‹tŒ¼-Œf‹Žˆ –­S‡ŽŒf(‹t’«‡‰ˆ –‘µ¼¶½§ œˆ2V¦L“U§ ‹Žˆ=¨ŽV´ ‹t©’—ª—’«z¬N±=‡#œ–}ˆ=‡Ž¾§=‡‰ª”±°‡‰ˆ=¸¸‹œ¬°-Œ¬²-‡o¿ˆ ±‹i-ŒU‹Žˆ –-­D‡ŽŒf¸‹t’«‡‰ˆ°¹*§’—“f§‹Ž“U§ ’«‘®Žœ– ‹tŠ Š Œ‡

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(5) ¦L’”¸‹t-ÀŠ5‘Œf³=‹t’«‡‰ˆ~-œ–-“‘‹Žˆ7©5 ±=‡‰ˆ=Žµ7ÁM‡ŽŒ(–Šœ“‘’—¿“‘‹Žª—ª«¬Ž› “V‡‰ˆ–’—±=‘Œ¾‹d–‹t’—–-’—“2ÂÄÃÆżÇÉÈ@ÊU»k’«¾¸‹œ¬°©5@Š5‡‰––’«©ª« -‡7¿ˆ ±²Ë̖f³ “f§²§ ‹tÎÄ ÍÈ ÃÏË~ÇÉÈ¸Ê ’”–*V¦=“f§ ‹Žˆ ¨Žœ‹t©ª«@‹Žˆ ±N-‡7¹*Œf’«-¾ÂÐà Å!Í Ç0@ÍÈ ÊUµ$Ñ.ˆ ‡Ž§=‘Œ“‘‹Ž–-œ–ҹӏ$¸‹œ¬@©5À“V‡‰ˆ0-œˆ0Ó§‹tdÏÍÈ § ‹Ž–Ó‹Žˆ¸V¦=“f§ ‹Žˆ ¨Žœ‹t©ª«$®F‹tŒU’—‹Žˆ “V*¸‹t-ŒU’Ô¦› š.

(6) HAL author manuscript. ¹*§ ’—“U§ ¹Ó7± œˆ=‡Ž-7–œ“V‡‰ˆ ±L´‚@‡‰@œˆ02V¦L“U§ ‹Žˆ=¨Žœ‹t©’”ª—’«‚¬ŽµN¶½§ œˆÕ–‘‘¯#’—ˆ ¨M-Œf‹Žˆ –­S‡ŽŒ-´ ¸‹t’«‡‰ˆ –2-‡O¹Ó‹tŒf±–@V¦L“U§ ‹Žˆ=¨Žœ‹t©’”ª—’«‚¬Õ¹Ód–§=‡

(7) ¹Æ§ oŠ Œf’«®L’—ª«‘¨Žœ±ÎŒ‡‰ª«i‡Ž­*Œfœ–’—± ³ ‹Žª”–‘µ ¶i–f§=‡

(8) ¹Ì§ ‹tV¦L‹Ž“V@Š5‘Œf³=‹t’«‡‰ˆÎ-œ–-–2“‘‹ŽˆÕ©5~“V‡‰ˆ –--ŒU³ “V-œ±Ö­S‡ŽŒ§=iˆ=‡ŽŒf¸‹Žª ª—’—ˆ=œ‹tŒ:¸‡#±=œª×µ¸Ø¼’”ˆ ‹Žª—ª«¬N¹7–³=¨Ž¨Žœ–-:‹tŠŠ Œ‡œ¦=’—¸‹t-(Š‘ŒU³=‹t’—‡‰ˆ-œ–-–©‹Ž–-œ±‡‰ˆ –-œ“V‡‰ˆ ±L´‚@‡‰¸œˆ~V¦L“U§ ‹Žˆ=¨Žœ‹t©’—ª”’«‚¬ÙµÚÑ.ˆÛ§ N“‘‹Ž–-N‡Ž­$‹ŽˆÚ’—ˆ0-Œf‹Ž“‘ª—‹Ž––¸“V‡ŽŒfŒœª—‹t’«‡‰ˆ @‡#± œªÜ›;§=@-Œf‹Žˆ–-­S‡ŽŒU¸‹t’«‡‰ˆÝ’—–}–f’—@Šª«-‡M’—¸Šª«œ@œˆ0‘µ2¶(‹Žª—–-‡d¨‰’—®Ž@Š‘ŒU³=‹F´ ’«‡‰ˆ ‹Žª=@‡‰@œˆ0–H‡Ž­ª”’—ˆ=œ‹tŒk‹Žˆ ±2Þ0³‹Ž±=Œf‹t’—“Ó­D‡ŽŒf¸–H‹Žˆ ±2–§=‡O¹ß§=‡

(9) ¹Û§ ’”–¼“‘‹Žˆ2©5³ –-œ± §=Œ‡‰³=¨‰§NງŽŒfˆ ’—–§=´‚ؼ’”–§=‘ŒÓV¦#Š‹Žˆ–’«‡‰ˆ –‘µ. inserm-00262035, version 1. }á ‘¬#¹‡ŽŒf±–‘âk¥k¦=“f§ ‹Žˆ=¨Žœ‹t©’—ª—’«z¬Ž›#㼏‘Œf³=‹t’«‡‰ˆ~-œ–-‘›=ä*‡‰¸‡Ž¨Žœˆ=œ’«‚¬(-œ–-‘›=å œ–’—±=´ ³ ‹Žª—–‘›•L“V‡ŽŒf:æ œ–‘›æ ŒU‹Žˆ –-­D‡ŽŒf¸‹t’«‡‰ˆ'µ ç. è éJê5ë'ì¾í¸î2ï¼ê5ðfìÀé. k¥ ¦=“f§ ‹Žˆ=¨Žœ‹t©’—ª—’«z¬Õ’—–(‹°¯Ž‘¬ÕŒfœÞ0³ ’—Œœ@œˆ0@­S‡ŽŒ¸©³ ’—ª—± ’”ˆ=¨M‹Š5‘Œf³=‹t’«‡‰ˆÖ-œ–-‘µ½ñ ®Žœ“V-‡ŽŒ$Ȩ̀ ‹Ž–À‹ŽˆdV¦=“f§ ‹Žˆ ¨Žœ‹t©ª«±’—–--Œf’«©³=’«‡‰ˆi’«­Hò¾Ȩ̀ ‹Ž– §=–‹Ž@±’—–--Œf’«©³=’«‡‰ˆ ‹Ž–È(›Ž­D‡ŽŒ‹Žˆ0¬:Š5‘Œf³=‹t’«‡‰ˆ@¸‹t-Œf’«¦ò@µHÑz­¹ “V‡‰ˆ –f’—±=‘Œk‹J-œ–-–-‹t’—–-’”“ÒÂÙÃóżÇÉÈ@Ê ‹Š5‘Œf³=‹t’«‡‰ˆ~-œ–-’—–‡Ž© ‹Ž’—ˆ=œ±;›#’«­;Èϒ”–ҏV¦=“f§ ‹Žˆ ¨Žœ‹t©ª«Ž›=©#¬(“V‡‰ˆ ± ’«’—‡‰ˆ ’—ˆ=¨¾‡‰ˆ7§= ‡ŽŒf±=‘Œ2–-‹t’—–-’—“‘–È ôöõ-÷}Ãùø

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(11) 5à š «› ­S‡ŽŒ‹Žˆ0¬:Š5‘Œf³=‹t’«‡‰ˆ2¸‹t-Œf’«¦ò@µHæ §=‹Ž––³ ¸Š ’«‡‰ˆ‡Ž­V¦=“f§ ‹Žˆ=¨Žœ‹t©’—ª—’«z¬Ž›‹Žª«§=‡‰³=¨‰§ ‹~ª—’—-ª«ª«œ–f–À–--ŒU’—ˆ=¨Žœˆ0*§ ‹Žˆ²§=2‹Ž––³ ¸Š ’«‡‰ˆd‡Ž­’—±=œˆ0’—“‘‹Žª—ª«¬i’—ˆ ±=‘Š5œˆ ± œˆª«¬i± ’—–-´ -Œf’«©³=-œ±‡Ž©–‘Œ®F‹t’—‡‰ˆ –‘›‰’—–H–-’—ª”ª0Þ#³ ’«-ºŒœ–--ŒU’—“V’«®ŽŽ›‰‹Žˆ ±@±=‡#œ–Hˆ=‡Ž§=‡‰ª—±­D‡ŽŒk’—ˆ –-‹Žˆ “V ’—ˆoŒ‘¨ŽŒœ–f–’«‡‰ˆdŠŒ‡Ž©ª«œ¸–œµºàӇ‰ˆ –f’—±=‘Œ ­D‡ŽŒÀ’—ˆ–-‹Žˆ “V¾§=ª—’—ˆ=œ‹tŒ Œf‘¨ŽŒœ––’«‡‰ˆMŠ Œ‡Ž©ª—œ Çɖ-³ ± ’«œ±Î’—ˆÝ–-œ“V’—‡‰ ˆ #µ ‰ÊUâ¸È  à 7¹*§=‘Œf Ē—–‹M¸‹t-Œf’«¦°‡Ž­V¦LŠª—‹Žˆ‹t-‡ŽŒ¬ ˜.

(12) HAL author manuscript inserm-00262035, version 1. ®F‹tŒf’”‹t©ª«œ–‘›‹d®Žœ“V-‡ŽŒ:‡Ž­“V‡0!~“‘’«œˆ–:‹Žˆ ±"(‹ŽˆÝV¦L“U§ ‹Žˆ=¨Žœ‹t©ª«(®Žœ“V-‡ŽŒ:‡Ž­º‘ŒŒ‡ŽŒf– ¹*’«§Ú·‘‘Œ‡ÖV¦#Š5œ“V‹t’«‡‰ˆ'µ æ*§=NV¦=“f§‹Žˆ=¨Žœ‹t©’—ª—’—‚¬ßŠ Œf‡ŽŠ‘Œf‚¬ß¹*’”ª—ª*ˆ=‡Ži’—ˆÚ¨Žœˆ=‘Œf‹Žª ©iŒ‘‹Ž’”ˆ=œ±Ö©0¬ÕÈ ’—ˆÖ–³“f§Û‹@‡L±=œª}ÇD©5œ“‘‹Ž³ –-i§=d$È #À±=‡ˆ=‡Ž¸§ ‹

(13) ®Žo§=d–‹Ž@ V¦#Š5œ“V‹t’«‡‰ˆÊ –-‡@Š5‘Œf³=‹t’«‡‰ˆo-œ–-–À“‘‹Žˆ ˆ=‡Ž ©5}‹tŠ Šª”’«œ±o’—ˆo‹@–’—¸Šª«$¹Ó‹

(14) ¬Žµ æ §=²Š5‡‰––’«©’”ª—’«‚¬Î‡Ž­:‹tŠ Šª—¬#’—ˆ ¨ÝŠ5‘Œf³ ‹t’«‡‰ˆß-œ–-–i-‡Û–’—³ ‹t’«‡‰ˆ –(¹*§=‘ŒNV¦0´ “f§ ‹Žˆ=¨Žœ‹t©’—ª—’«z¬d’—–Àˆ ‡ŽÀ¨‰’«®Žœ& ˆ %('$)+*-,).*¼§ ‹Ž–ÀŒœ“Vœ’«®Žœ±²‡‰ˆ ª«¬oª—’—(’«-œ±M‹t--œˆ0’«‡‰ˆÛÇÉå ‡t´ ¸‹Žˆ=‡šœÿŽÿt™L»¾•L“f§@‡

(15) ¬Ž‘Œ°šœÿŽ/ÿ 0ʸ‹Žˆ±ß’«¸’—–¸“‘ª—œ‹tŒ(§ ‹t¸§ ‘ŒM‹tŒM–f’«³ ‹t’«‡‰ˆ –NÇD­S‡ŽŒ ’—ˆ –-‹Žˆ “VÀ¹*§=œˆ~± ‹t‹§‹œ®Ž$‹:ˆ=‡‰ˆL´×V¦=“f§‹Žˆ=¨Žœ‹t©ª«$“V‡ŽŒŒœª—‹t’—‡‰ˆ~¸‹t-ŒU’Ô¦ ÊH¹*§=‘ŒÀŠ‘Œ´ ³=‹t’—‡‰ˆd-œ–-–*¹*’—ª—ª5ˆ=‡Ž©5}Œ‡Ž©³–-‘µ æ § ’—–ÓŠ‹tŠ5‘Œ’—–º‹Žˆd‹t--œ@Š-‡@V¦#-œˆ ±o–‡‰@}§=‘‡ŽŒ‘’—“‘‹Žª;Œœ–³ ª«–º‹t©5‡‰³=º-Œf‹ŽˆL´ ­S‡ŽŒf(‹t’«‡‰ˆ –¼¹*§ ’—“U§¾Š Œfœ–-‘Œ®ŽºV¦L“U§ ‹Žˆ=¨Žœ‹t©’”ª—’«‚¬‹Žˆ ±:-‡$V¦LŠª«‡ŽŒÓ‹J¹Ó‹

(16) ¬:‡Ž­ V¦L-œˆ ± ’—ˆ ¨ Š‘ŒU³=‹t’—‡‰ˆ –Ӑ-œ–-–-‡¸“V‡‰@Šª—V¦7–’«³‹t’«‡‰ˆ –‘µkæ § ’”–Ò¹º‹œ¬i’—–Ӑ-‡@¿ˆ ±i‹-Œf‹Žˆ –-­D‡ŽŒf¸‹F´ ’«‡‰ˆÝËƖ³ “U§°§ ‹tÕÌ ÍÈ Ã Ë(ÇÉÈ@ÊÀ’—–JV¦L‹Ž“Vª—¬M‡ŽŒ¾‹tŠ Š Œf‡œ¦=’—¸‹t-œª«¬dV¦=“f§‹Žˆ=¨Žœ‹t©ª«¸‹Žˆ ± -‡(Œœª«¬~‡‰ˆo§=¾Š5‘Œf³=‹t’«‡‰ˆM± ’—–--Œf’—©³=’«‡‰ˆ(‡Ž­!ÂÌÇDV¦#Š Œfœ––-œ±d‹Ž–À‹@­D³ˆ “V’«‡‰ˆi‡Ž­72ÍÈ Ê ’—ˆ ± ³ “Vœ±Î©#¬ §=iŠ5‘Œf³=‹t’«‡‰ˆ –‡Ž­Ý~ÍÈ µÕ•L’”ˆ “V~V¦=“f§‹Žˆ=¨Žœ‹t©’—ª—’—‚¬Î’”–‹²®Ž‘Œ¬Õ–--Œf’—ˆ=´ ¨Žœˆº‹Ž––³ ¸Š ’«‡‰ˆ'›‰¹Ó$§ ‹œ®ŽJ©5‘œˆ(ª«œ±(-‡:V¦=‹Ž¸’—ˆ=J‹¾¹Óœ‹t¯Ž‘Œº‹Ž–f–³ @Š ’—‡‰ˆ'›‰§ ‹tÓ‡Ž­ –-œ“V‡‰ˆ ±i@‡‰@œˆ0ºV¦L“U§ ‹Žˆ=¨Žœ‹t©’—ª”’«‚¬NÇÉò:È%§ ‹Ž–º–‹Ž@J¿ Œf–Ó‹Žˆ ±7–-œ“V‡‰ˆ ±i@‡‰¸œˆ–‹Ž– È2ÊUµJ¶§‹œ®Ž@“V‡‰ˆ –’—± ‘Œœ±d§=-œ–-–J‡Ž­Œ‘¨ŽŒfœ––’«‡‰ˆ²“V‡0! ~“‘’«œˆ–$‹Žˆ ±N§=-œ–-–J‡Ž­ §=‡‰@‡Ž¨Žœˆ=œ’«z¬²‹Ž–}± œ–“VŒf’«©5œ±N©0¬àӇ‰¸@œˆ=¨Žœ–}‹Žˆ1± 0‹Ž“‘Þ0(’—ˆL3´ 2$‹Ž± ±‹°Ç šœÿŽÿ ŽÊUµ2¶ § ‹œ®Ž(ˆ ‡ŽJ‡Ž©‹Ž’—ˆ=œ±²©0¬N§ ’—–J¹º‹œ¬°‹iŠ‹tŒ’—“‘³ ª”‹tŒfª«¬o‹tŠ Š5œ‹Žª—’—ˆ=¨iˆ=‘¹ -œ–-‘»¼§=‡

(17) ¹Ó‘®Ž‘Œœ› ‹Žª«‡‰ˆ=¨²§=~¹º‹œ¬Ž›Ò¹i§ ‹œ®Ži‡Ž© ‹Ž’”ˆ=œ±Î–‘®Ž‘Œf‹ŽªÓ§=‘‡ŽŒ‘’—“‘‹ŽªÓŒœ–³ª«–:¹À§ ’—“f§Î¸‹œ¬Î©5 ³ –-‘­É³ ª5­S‡ŽŒ*­D³=³ Œ}Œ!  V¦=’«‡‰ˆi‡‰ˆo§ ’”–º-‡ŽŠ’—“tµ æ §=$‡ŽŒ¨‰‹Žˆ ’—·œ‹t’«‡‰ˆ7‡Ž­ §=$Š‹tŠ5‘Œº’—–º‹Ž–º­S‡‰ª—ª—‡

(18) ¹*–‘µkñJ–º‹ŠŒ‘ŒœÞ#³ ’—–’«-Ž›L’—ˆ7–-œ“V’«‡‰ˆ ˜#›k¹i¿ Œf–“V‡‰ˆ –’”±=‘Œª—’”ˆ=œ‹tŒ:-Œf‹Žˆ–-­S‡ŽŒU¸‹t’«‡‰ˆ –¹*§ ’—“U§ÝŠ Œfœ–-‘Œ®Ž7V¦L“U§ ‹Žˆ=¨Žœ‹t©’—ª”’«‚¬Ž› ‹~-‡ŽŠ’—“‹Žª—Œœ‹Ž±=¬M–-³± ’«œ±N©05¬ 4Jœ‹Žˆ‹Žˆ 7± 6k‘Œf±³ “‘“‘’Ç šœÿŽÿt™Ê$‹Žˆ 1± 4Jœ‹Žˆ‹Žˆ ±M¶‡‰ª—­S Ç šœÿŽÿt™ÊU»º§ ‘Œ(¹Ó7±’—–-’—ˆ=¨‰³’—–§°©5‘‚¹Ó‘œˆÖ–-œ“V‡‰ˆ ±L´‚@‡‰¸œˆ@‹Žˆ ± ¨‰ª«‡Ž©‹ŽªV¦L“U§ ‹Žˆ=¨ŽV´ .

(19) HAL author manuscript inserm-00262035, version 1. ‹t©’—ª—’«z¬»0ˆ=‡‰ˆL´‚ª—’—ˆ œ‹tŒk-Œf‹Žˆ –-­D‡ŽŒf¸‹t’«‡‰ˆ–k‹tŒ*‹Žª—–-‡¾“V‡‰ˆ–’—±=‘Œœ±;µ¼æ § œˆ@’—ˆ@–-œ“V’«‡‰ˆ8$¹ “V‡‰ˆ –’—±=‘Œ¸ª”’—ˆ=œ‹tŒ@-Œf‹Žˆ –­S‡ŽŒf(‹t’«‡‰ˆ –2¹*§ ’”“f§Û‹Ž“f§’«‘®ŽdV¦=“f§ ‹Žˆ=¨Žœ‹t©’—ª—’«z¬âo§=d³–-o‡Ž­ Œœ–’—± ³‹Žª—–’—– § ’—¨‰§ ª—’«¨‰§0-œ±i‹Žˆ ±d¹Ó¾¨‰’«®Ž¾V¦=‹Ž“VJŠ‘ŒU³=‹t’—‡‰ˆo-œ–-– ­D‡ŽŒ*§ :ˆ=‡ŽŒf¸‹Žª ª—’—ˆ=œ‹tŒk@‡L±=œª=‹Žˆ ±@‹Žˆ@V¦=‹Ž@Šª—º’”ˆ@‹}¸‹t“f§=œ±¸Š‹Ž’«Œf–k±=œ–f’«¨‰ˆ'µH•Lœ“V’«‡‰9ˆ }Š Œœ–œˆ–‹ @‡ŽŒ¾œ@Š’«Œf’—“‘‹Žª‹tŠ Š Œ‡‰‹Ž“U§d-‡¸§ }¨Žœˆ=‘Œf‹Žª;“‘‹Ž–-Ž›’—ˆ7Š‹tŒ’—“‘³ª—‹tŒ ’—ˆ7§=:“‘‹Ž–-:‡Ž­¼‹Žˆ ’—ˆ-ŒU‹Ž“‘ª—‹Ž––¾“V‡ŽŒŒfœª—‹t’«‡‰ˆ ¸‡#±=œª×» ¹Ó(V¦=‹Ž¸’—ˆ=@©5‡Ž§Ýª—’”ˆ=œ‹tŒ¾‹Žˆ ±ÝÞ#³ ‹Ž±=Œf‹t’”“¸–-‹t’—– ´ ’—“‘–‘µØH’—ˆ ‹Žª—ª«¬Ž›H‹°ª—‹Ž–-–-œ“V’«‡‰ˆóÇD¹*§ ’”“f§Õ’—–ˆ ‡Ž’«¨‰§0ª«¬Ýª—’”ˆ=¯Žœ± -‡²§=iŒœ–-‡Ž­ §= Š‹tŠ5‘ŒWÊ:Š Œœ–-œˆ0–@–-‡‰@o-œ“U§ ˆ ’—“‘‹Žª ’”ˆ ± ’—“‘‹t’«‡‰ˆ–‘›k± :’ (“‘³ ª—-‡¿ˆ±Îœª”–-‘¹*§=‘ŒŽ›Ò­S‡ŽŒ Š‘Œf­S‡ŽŒf(’—ˆ=¨2‹@Š5‘Œf³ ‹t’«‡‰ˆo-œ–-*³–’—ˆ=¨@‹tŠ Š Œf‡œ¦=’—¸‹t’«‡‰ˆ –º©‹Ž–-œ±o‡‰ˆd@‡‰¸œˆ–‘µ ;. ^U_ `. ë ï¼êBAë;ðDCE?Óê5ðfìÀé ìFêë? é@CEFœì*ëHGI?Óê5ðfìÀé@CKJL=@ðfïM= 2N ëAPO CEAëBQRASAUTM ï =@? @é VRAW?YX@ð[ZUð ê]\ <>=@? ?. acbdfeWghWiMj gBkmlnjpogEqsrut d]jv. ñ ŒU‹Žˆ ±=‡‰wyx~šº®Žœ“V-‡ŽŒÓÈ § ‹Ž–Ò‹Žˆ¸V¦=“f§ ‹Žˆ=¨Žœ‹t©ª«À± ’”–--Œf’«©³ ’«‡‰ˆ’—­‹Žˆ ±@‡‰ˆª«¬’—­‹Žˆ0¬ Ú Š‘ŒU³=‹t’—‡‰ˆi‡Ž­!È%§‹Ž–º§=¾–‹Ž@}± ’—–-Œf’«©³=’—‡‰ˆ'µ!æ §’—–’”@Šª—’«œ–§ ‹t§=$®t‹tŒf’—‹Žˆ “V ¸‹t-Œf’Ô¦i‡Ž­kò¾È(›¹*§=‘Œ:ò%’—– ‹@Š5‘Œf³=‹t’«‡‰ˆd(‹t-Œf’Ô¦5›³–-©5}§=:–‹Ž@‹Ž– § ‹t ‡Ž­HÈ~µkÑ.P­ zĒ—–º§ ’—–*¸‹t-Œf’Ô¦7¹:³ –-À§ ‹œ®Ž ò z}ò |°> { à z ­S‡ŽŒ‹Žˆ0¬¸‹t-ŒU’Ô¦ ò ~€ ý ›Ž§=–-‘H‡Ž­ (xR7Š‘ŒU³=‹t’—‡‰ˆ(‹t-Œf’—“Vœ–‘µ•L³ “U§@‹J(‹t-Œf’Ô¦ ’—– “‘‹Žª—ª«œ±o‹ŽˆMV¦L“U§ ‹Žˆ=¨Žœ‹t©ª—:¸‹t-Œf’Ô¦o‹Žˆ ±d“‘‹Žˆd©}¹*Œf’«--œˆ z ƒô ‚!„ ×÷ > à † [ú ‡ pˆ Šú ‰‹ Œ à †Ç ‡cp‰‹ Ê Žˆ ‰‹ ¹*§=‘Œ ‰‹ ’—–*9‹ x (‹t-Œf’Ô¦o¹*§ ’—“U§d§ ‹Ž–À‹Žª—ª;’«–*œª«œ@œˆ0– œÞ#³ ‹Žª;-‡²š k›‹Žˆ ± ‡ ’—– §=  xݒ—±=œˆ0’«‚¬7¸‹t-Œf’Ô¦5µæ §=¾–-œ“V‡‰ˆ±oŒ‘Š Œœ–œˆ‹t’«‡‰ˆM’—–’—ˆ0-‘Œœ–-’—ˆ=¨2©5œ“‘‹Ž³ –- .

(20) Ž‹ ˆ ± ‡ ‰‹ ‹tŒd’—±=œ¸Š‡Ž-œˆ0@‹Žˆ ±Ö‡ŽŒ§=‡Ž¨Ž‡‰ˆ‹ŽªÜµÛæ §=‘¬ ­D‡ŽŒf ‹ŽˆÛ‡ŽŒf§=‡‰ˆ=‡ŽŒf¸‹Žª ©‹Ž–’—– ’”ˆi§=¾–-Š‹Ž“V{‘ ý ‡Ž­U"x°V¦=“f§ ‹Žˆ ¨Žœ‹t©ª«(‹t-Œf’—“Vœ– ‹Žˆ ±d¹:§‹œ®Ž ‰‹. HAL author manuscript. }ô ×÷ ¾ô Ô÷!à ¾ô. ö÷. z ƒ‚Š„ Ez ƒ‚[’“„ ”’ >z ƒ‚+•B‚D’–„ n•B ”’. inserm-00262035, version 1. ô ×÷ ô ÷ à ô ÷ ú z˜ƒô — ‚!„ ×÷ Ã>z ôƒ‚!™›šœ„ 3™›šz÷ úž Ÿ úž Ÿ úž Ÿ z ô¡‚!„ ×÷ Ã>z ô¡‚ š“¢ £ „ š“¢ £ ÷ û ¹À’«§z ô¡‚!„ ×÷ Ã>z ô¡‚!„ ×÷ z ôƒ‚Š„ ×÷ ü ؼ’”ˆ ‹Žª—ª«¬Ž›§ 7ŒU‹Žˆ=¯ ‡Ž­}z ô¡‚!„ ×÷ ’”–™’—­ †ß¤ à ˆoà ™L›Jšo’—­†Öà ™Lû¥ˆà ¦ ™L›§  šo’«­ †7ÃÙ ¦ ™LûRˆà ™¸‹Žˆ ±ݒ«­U†7à ¦ ™LR û ˆcà ¦ ™Lµ †*‡Ž‹t’—‡‰ˆ –‘â’”ˆo–-‡‰@:“‘‹Ž–-œ–*§=:± ’”@œˆ –’«‡‰ˆ7‡Ž­k‹@¸‹t-Œf’«¦7¹*’”ª—ª©¾’”ˆ ± ’—“‘‹t-œ±o‹Ž– ‹¾–³=©–f“VŒf’«Š ‘›‰’—ˆ2‡Ž§ ‘ŒÒ“‘‹Ž–-œ–¹*§=‘Œ§= ±’—@œˆ –’—‡‰ˆ’”–H‡Ž©0®L’«‡‰³ –’—k¹*’—ª—ª#©5‡‰¸’«--œ±'â ­S‡ŽŒ’—ˆ –‹Žˆ “V*§=¨ ©x9²¸‹t-Œf’Ô¦¸¹*§’—“f§7§ ‹Ž–Ó‹Žª—ª’—–ҏœª«œ¸œˆ–ӏœÞ#³ ‹Žª-‡7š °¹*’—ª”ª=©5 ±=œˆ=‡Ž-œ± ‰‹ ‡ŽŒ ‰‹ý µ z ƒ‚Š„ z ƒ‚ ’ „ ’ >z ƒ‚[‚ ’ „ - ’. ^U_“^. ªtžhWj gBrŒqsrgh§v/« ¬HruogEqtn¬MhmvŽ­7e§t dfe¤®§rujv/j rs¯Mj°v/jd]¬±h§²U³!o¬Mojh±q j´bWdue§gBh§iHj gBkmtžl tnqŠµ. ;‘·R¸ Ÿ §=N–-Š‹Ž“V²‡Ž­¾ª”’—ˆ=œ‹tŒ(-ŒU‹Žˆ –-­D‡ŽŒf¸‹t’«‡‰ˆ –~­DŒ‡‰º¹ ý -‡»¹¥¼:› ¹À’«§Ž½ ¾ k›!¹*§’—“f§ŠŒœ–-‘Œ®Ž7–-œ“V‡‰ˆ ±L´‚@‡‰¸œˆV¦L“U§ ‹Žˆ=¨Žœ‹t©’—ª”’«‚¬Žµdæ § ¸­S‡‰ª”ª«‡

(21) ¹*’”ˆ=¨o§=‘‡ŽŒœ “f§ ‹tŒf‹Ž“V-‘ŒU’«·‘œ–*§ œ–-¾-Œf‹Žˆ –­S‡ŽŒf(‹t’«‡‰ˆ –‘µ ý Èn,{¹ ¼ '$)œÇËÉ!Ç!).ÍsÇ+ɨÉ!ÇDÎ.,Æ$Ïy̘,Ð ¿(À±Áf ¡ Á]à ‹ŒÄÅ *–ÆEÇD%s)}Ȕ)œ%ƴɖÊË,s).̘%sȔ*-,Æ9Ê+) ,Ì°¹ ¶. ̘Ç!ÆÈYÇDÑfÎËқ%ƛÓfÇD%fÔË* Å *”È”Õ7֞Ȗқ%sÈ×*“ÉcÔ[Ç Å ,ÆfÓsÉØÈn,@·¨¸ Ÿ * Ê{*”Èm*ÙÉ{)DǞ'$)DÇ+ɊÇËÆÈ Ç[Ï5ÔËÕ8%8Ì9%Ȕ).*:Ñ Ú Òu*”Î!ÒÎ[%ƏÔ.Ç Ú ).*”È-È ÇËÆ"%/É Û ¼. ý Ã. „ >z. Ý. ¼¨Ü}¼. „. ýû.

(22) ý. ý. ý Ã. ‡ ȖÒ]ǁ) , Ú ÍÇ[ΊÈn,).É Ú Ò]ÇË)DÇ+ÞRz ¼ ~ߑ ¼ %ÆEÏ Ü ¼ „ *“ɘÉ.à ÎËÒȖқ%sÈ Ü ¼ „ Ü |¼ „ ¼ á â #(, Ê Ü ÊË,)+ÌãȖÒuà›É8%Æä,)ËȖқ,Æ$,s).̘% Å Ô[%/É.*“É á *–Æä%ÏÏ*”È”*-,ÆäȖÒ]Ç!ÕÌ@à›É+ÈÉË%sȔ*“É“Ê+ՐȖÒ]Ç Î[,Æ$Ïs*–È”*-,Æ7å5æ â # æ çèÞ Ú Ò´ÇË)DǨçŽ~¹7é. Ã. HAL author manuscript inserm-00262035, version 1. ¡ ÂÂ$ë ¤ Ñz$’—–J“‘ª«œ‹tŒJ§ ‹tJ’—­Wzì~1‘ ¼ ›­S‡ŽŒ$‹Žˆ0¬5z ú ~7‘ ¼ ¹Ó§‹œ®Ž9zØz ú z | ~1‘ ¼ ‹Žˆ ± ’«:’—–:œ‹Ž–’—ª«¬²®Ž‘Œf’«¿ œ±Ý§ ‹t’«í­ z Ÿ ~Ž‘ ý › Ü z Ÿ Ü | ~&‘ ¼ µiæ §#³ –:‹Žˆ0¬“V‡‰@Š5‡‰–’«’«‡‰ˆ ‡Ž­§=œ–‚¹Ó‡ß-Œf‹Žˆ –-­D‡ŽŒf¸‹t’—‡‰ˆ –‘›$“V‡‰@Š‹t’«©ª—N¹*’—§ §=± ’—@œˆ –f’«‡‰ˆ –‘› ŠŒœ–-‘Œ®Žœ– –-œ“V‡‰ˆ ±L´‚@‡‰¸œˆ7V¦L“U§ ‹Žˆ=¨Žœ‹t©’”ª—’«‚¬ ›º¹*§ ’”“f§ÛŠ Œf‡

(23) ®Žœ–~§ ‹t~¸‹t-ŒU’—“Vœ–¸‡Ž­$§=N­S‡ŽŒf –-‹t-œ±N’”ˆi§=¾æ §=‘‡ŽŒœ9©œª—‡‰ˆ=¨@-y‡ ·¨¸ Ÿ µ †*‡Ž-Î§ ‹tM’«­È3§ ‹Ž–d–-œ“V‡‰ˆ ± @‡‰@œˆ05 z ú ~î‘ ý ›}’«@­ Û Š Œœ–-‘Œf®Žœ–d–-œ“V‡‰ˆ ± @‡‰@œˆ0@V¦L“U§ ‹Žˆ=¨Žœ‹t©’—ª”’«‚¬Õ¹d³ –-@§ ‹

(24) ®Ž© Û1z ú Û | ~>‘ ¼ µÕæ*§ ‹t@‹Žª—ªº¸‹t-Œf’—“Vœ– Š Œœ–-‘Œ®L’—ˆ=¨²V¦=“f§ ‹Žˆ=¨Žœ‹t©’—ª—’«z¬Õ§ ‹

(25) ®Žd§=i­D‡ŽŒf[‡Ž­À§ dæ §=‘‡ŽŒœ “‘‹ŽˆÛ©5o–-‘œˆÖ©#¬ z ú à ‡ µæ § ’—–J’—@Šª”’«œ–*§‹t}¹@§ ‹

(26) ®Žy  Û1Û | w à z¸› ­S‡ŽŒ¾–-‡‰¸@ zï~»‘ ¼ µ:¶(“‘‹Žˆ žú  Ÿ žú  Ÿ ¹ Œf’«-8 Û7Û | I à z

(27) ž z

(28) | µdØ=Œ‡‰Š Œ‡ŽŠ5‡‰–’—’«‡‰ˆßštµ Lš~‡Ž­ ¥Ò‹t-‡‰ˆÙÇ šœsÿ s‰ÊU›§ ’—– ’—@Šª—’—œ– § ‹t{ Û | L à ð×z¸›;¹À§=‘Œc ð’—–$‹Žˆ°’—–-‡‰@‘-ŒU’—“:‡ŽŠ5‘Œf‹t-‡ŽŒ:­SŒ‡‰ñ  ¹¥¼Ï-‡ ¹ ý µ æ §0³¨– Û<ò à zØð | w à z Ü »!§=‘Œ Ü L à ð | ¹À§ ’—“f§²’—@Šª—’«œ– §‹t Ü(Ü | à ‡ µ¾æ §=‘Œf ’—–º‹Žˆo‹Ž± ± ’«’«‡‰ˆ‹Žª“V‡‰ˆ ± ’—’«‡‰ˆ7¹*§=œˆ~¹}‹tŠ Šª—y¬ Û -‡2§=}¸‹t-Œf’«¦ ‰‹‰ý ¹Ó}³–-§ ‹œ®Ž Û ‰‹ý ß Ã ç ‰‹ ¼ › ¹À§=‘Œ  çŽ~¹Nµ †*‡O¹Æ’«:“‘‹ŽˆÝ©5(–‘œˆ § ‹t( ð | “‘‹ŽˆÝ©5¸Œ‘Š Œfœ–-œˆ-œ±Î©#¬²§ ~“V‡‰@Š5‡‰–’«’—‡‰ˆ‡Ž­ ‹Žˆß’—–-‡‰@‘-ŒU’—“7‡ŽŠ‘ŒU‹t-‡ŽŒ¸­SŒf‡‰ã  ¹ ý - ‡ ¹ ý ‹Žˆ ±Ö§ d–³=©=´×®Žœ“V-‡ŽŒ~‡ŽŠ‘ŒU‹t-‡ŽŒœâ Ü Ã ‡ „ ý ó¼uý „ ý › ¹À§=‘Œ ‡ ¼ „ ý ô à ‡ ¼ „ ¼@õ÷ö¼ „ ý — ¼

(29) $’—–~§=  ø-–f³=©0®Žœ“V-‡ŽŒi‡ŽŠ5‘Œf‹t-‡Ž[Œ ù֋Žˆ ± ¼ ó!f ý „ ý ’—–k‹Žˆ¸’—–‡‰@‘-Œf’—“Ӑ-Œf‹Žˆ –­S‡ŽŒf(‹t’«‡‰ˆdÇ ó!fý „ ý ó uý | „ ý à ‡ ÊUµkñJª—–-‡=›‰¨Ž‘‡‰@‘-ŒU’—“‘‹Žª—ª«¬Ž› Ü È “‘‹ŽˆM©5:’—ˆ0-‘ŒŠ Œf‘-œ±M‹Ž– § :Š Œ/‡ ú-œ“V’«‡‰ˆM‡Ž­k§=¾‡ŽŒf’«¨‰’”ˆ ‹Žª'®Žœ“V-‡ŽŒ}È扈N‹~–³=©–-Š‹Ž“V ‡Ž­± ’—@œˆ –f’«‡‰ˆ ½›Œ‘ŠŒœ–-œˆ0-œ±M’—ˆd‹(‡ŽŒ§=‡‰ˆ=‡ŽŒU¸‹Žª;©‹Ž–f’—–‡Ž­k§ ’—–*–³=©–-Š‹Ž“V¾¹*§=‡‰–- ®Žœ“V-‡ŽŒf–À‹tŒf¾§=}Œ‡O¹*– ‡Ž­ Ü µ ê. û.

(30) Ñ.ˆdŠ‹tŒ’—“‘³ ª”‹tŒœ›L-Œf‹Žˆ –-­D‡ŽŒf¸‹t’«‡‰ˆ–­SŒf‡‰K¹ ý -‡˜¹ ý “‘‹Žˆd©5}¹ Œf’«--œˆ ô Ž÷ Ãÿþ. Û ƒü›„ ý. ó  ‰‹. û. HAL author manuscript inserm-00262035, version 1. ¹*§=‘Œ ó ’—–À‹9x ’”–-‡‰@‘-Œf’—“¾-Œf‹Žˆ –-­D‡ŽŒf¸‹t’«‡‰ˆ;µÓñJˆdV¦=‹Ž@Šª«:‡Ž­H–f³ “f§N¸‹t-Œf’—“Vœ– ‹tŒວ=‡‰ª—œ–-¯0¬7±=œ“V‡‰@Š5‡‰–’«’—‡‰ˆi‡Ž­¼V¦=“f§‹Žˆ=¨Žœ‹t©ª«¸‹t-Œf’—“Vœ–‘µ Ñz¾’”–}“‘ª«œ‹tŒ}§ ‹t}-Œf‹Žˆ –­S‡ŽŒf(‹t’«‡‰ˆ –$¨‰’«®Žœˆ’—ˆæ*§=‘‡ŽŒœ š2Š Œœ–‘Œ®Ž2V¦L“U§ ‹Žˆ=¨ŽV´ ‹t©’—ª—’«z¬(‡Ž­¼§=¾¿ ŒU–-@‡‰@œˆ0 -‡0‡=µæ §0³–‘›=­S‡ŽŒ ˆ ‡ŽŒf¸‹Žª;± ’”–--Œf’«©³ ’«‡‰ˆ –‘›’—­±Ûã~©·¨¸ Ÿ › ’«@Š Œœ–-‘Œf®Žœ–dÇD¨‰ª«‡Ž©‹ŽªSʏV¦=“f§ ‹Žˆ ¨Žœ‹t©’—ª—’«z¬ŽµÛØ=Œ‡‰<§’—–¹M± œ± ³ “Vo‹Žˆß’—ˆ0-‘Œœ–-’—ˆ ¨ §=‘‡ŽŒ‘’—“‘‹Žª¼“V‡‰ˆ –-œÞ#³=œˆ “VŽâ§=‘Œ‹tŒf:’—ˆo¨Žœˆ=‘ŒU‹Žª –-‘®Ž‘Œf‹Žª ®F‹Žª”’—±iŠ5‘Œf³ ‹t’«‡‰ˆd± ’—–-´ -Œf’«©³=’—‡‰ˆ –'­D‡ŽŒ¼‹À¨‰’«®Žœˆ2–-‹t’—–-’”“tµ¼æ §’—–;’—–¼ˆ=‡Ž!–f³=ŒŠ Œf’”–’—ˆ=¨’«­L¹ÓÓ“V‡‰ˆ –f’—±=‘Œ Œfœ–--Œf’—“V-œ± Š‘ŒU³=‹t’—‡‰ˆ –‘›H­S‡ŽŒ2’—ˆ –‹Žˆ “V(Š5‘Œf³=‹t’«‡‰ˆ ‡‰ˆÕ–f³=©0®Žœ“V-‡ŽŒU–‘µ²ÁM‡ŽŒi–³=ŒŠ ŒU’—–’—ˆ=¨o’—– §=$­D‹Ž“Vº§ ‹t‘› ’«­;È%§ ‹Ž–º‹ˆ ‡ŽŒf¸‹ŽªV¦L“U§ ‹Žˆ=¨Žœ‹t©ª«¾±’—–--Œf’«©³=’«‡‰ˆ'›Ž§=‘ŒfJV¦=’—–-ÓŒ‘¨‰³L´ ª—‹tŒ-Œf‹Žˆ –­S‡ŽŒf(‹t’«‡‰ˆ –‘›0¹*§ ’—“U§2Š Œœ–-‘Œ®Ž*V¦L“U§ ‹Žˆ=¨Žœ‹t©’—ª”’«‚¬2©³=ˆ ‡ŽÒ§=*±’—–--Œf’«©³=’«‡‰ˆ ‡Ž­§  –-‹t’—–-’—“‘–±=‘Š5œˆ ± ’—ˆ ¨*‡‰ˆ(È~›‰­D‡ŽŒÒ’—ˆ –‹Žˆ “V§=Jວ ‡‰ª«œ–-¯#¬±=œ“V‡‰@Š5‡‰–’—’«‡‰ˆ2‡Ž­ ‹ŽˆNV¦=“f§‹Žˆ=¨Žœ‹t©ª«@®t‹tŒf’—‹Žˆ “V2¸‹t-Œf’«¦â*“V‡‰ˆ–’—±=‘}Œ z~"·¨¸ Ÿ Œ‘¨‰³ª—‹tŒœH» zÄÃ%ËË | »!Ë Š Œœ–-‘Œ®Žœ–k–œ“V‡‰ˆ ±L´‚@‡‰@œˆ0HV¦L“U§ ‹Žˆ=¨Žœ‹t©’”ª—’«‚¬»’«­=¹Ó§ ‹œ®Ž‹$–-‹t’—–’—“ÂÙÃóżÇÉÈ2ÊU›’— “‘‹Žˆ¸©5º¹ Œf’«--œˆ à Å!Í Ç @ÍÈ ÊU›¹À’«§ ÅiÍ ÃóÅ 5Ë — ú µHÑz­È§‹Ž–‹}ˆ=‡ŽŒf¸‹ŽªLV¦=“f§‹Žˆ=¨Žœ‹t©ª« ± ’—–--Œf’—©³=’«‡‰ˆ'› ’—À’—–À‹Žª—–-‡7§=“‘‹Ž–-2­D‡ŽŒ Æ ÍÈ ‹Žˆ±M§=œˆN®t‹Žª—’—±M’”ˆ=­S‘Œfœˆ “V:­D‡ŽŒ*Âϓ‘‹Žˆ²©5 ±=‡‰ˆ=$œ’«§=‘Œº©#¬¸Š5‘Œf³ ’—ˆ=¨È ‡ŽŒNÈ(Í µkÑ.Ó“‘‹Žˆi©5J®Ž‘Œf’«¿ œ±~§ ‹tº§=$‚¹Ó‡¸’—ˆ=­D‘Œœˆ “Vœ– ‹tŒ¾Œœ‹Žª—ª—¬~± ’ 5‘Œœˆ0‘µ æ ‡Õ¸‹t¯ŽM§’—ˆ=¨‰–(¸‡ŽŒM“V‡‰ˆ “VŒ‘-°“V‡‰ˆ –’”±=‘Œ(‹ ª”’—ˆ=œ‹tŒ¸–-‹t’—–’—“ÎÇD‡Ž­$§=N‚¬#Š ± ’—–“‘³ –f–-œ±¸’—yˆ #µ ˜‰ÊUâHÂÙ à  | È~µHÑz­'Èϒ—–kV¦=“f§‹Žˆ=¨Žœ‹t©ª«$‹Žˆ ±(ˆ ‡ŽŒf¸‹Žª ³ ˆ±=‘Œ§=Jˆ0³ ª”ª §¬#Š5‡Ž§=œ–’—–'-‡*©Ò-œ–--œ±'›t¹“‘‹Žˆ:³ –-‹Š5‘Œf³ ‹t’«‡‰ˆ¾± ’—–-Œf’«©³=’—‡‰ˆÇD§ ‹t¼’—–'¹ÓÒ³ –- ‹ŠŒ‡Ž©‹t©ª—’—‚¬@“V‡‰ˆ ± ’«’—‡‰ˆ ‹Žª‡‰ˆiÈ ôöõ-÷ ÊU» ’”ˆ(§ ’”––’—³ ‹t’«‡‰ˆ ÍÈ ÃóË:È~›#¹À’«§iËË | > à z ‹Žˆ  ± zù‹ŽˆÝV¦=“f§ ‹Žˆ ¨Žœ‹t©ª«~(‹t-Œf’Ô¦5›!’—–¾‹Žª”–-‡dV¦=“f§ ‹Žˆ=¨Žœ‹t©ª«Ž»–-‡=›H’«­¹Ó(Œf‘¹ Œf’«-@§= –‹Ž@N–‹t’—–-’—“d‹Ž–(  à  | Ë — ú Ë:Èà  Í | [ ÍÈ ¹ÓM“‘‹Žˆ½‹Žª—–-‡ ³–-M‹ÝŠ5‘Œf³=‹t’«‡‰ˆ.

(31) HAL author manuscript inserm-00262035, version 1. ± ’—–--Œf’—©³=’«‡‰ˆ©‹Ž–-œ±Ù‡‰ˆ §=Š5‘Œf³=‹t’«‡‰ˆ ‡Ž­ÚÍÈ ÇD§ ‹td’—–o³ –’”ˆ=¨Õ‹ßŠ Œ‡Ž©‹t©’”ª—’«‚¬ “V‡‰ˆ ± ’«’«‡‰ˆ‹Žª!‡‰ˆ È Í ôÔõ ÷ ÊUµæ*§=œ–-2‚¹Ó‡M± ’—–-Œf’«©³=’—‡‰ˆ –*‹tŒ¸±’‘Œfœˆ‘â$¹Ó¸’—ª—ª—³ –-Œf‹t-’— ¹*’«§Ý‹d–f¸‹Žª—ªkV¦=‹Ž@Šª«(¹*’«1§ î à #µiæ!‹t¯Ž  | à ÇəLü ˜ û û™L÷ü ‰™Lû™Lü Ýsû Ê@‹Žˆ ±ÎÈ | Ã Ç  štü s#û™Lü—šŽšœÿ#û  štü ™‰ÿ‰ÊoÇD§ ’”–$®F‹Žª—³ ‡Ž­ºÈ6¹Ó‹Ž–¾’”ˆ ±=‘œ±²‡Ž© ‹Ž’—ˆ=œ±‹Ž–:‹iŒœ‹Žª—’«·œ‹t’«‡‰ˆ ‡Ž­J§ Œ‘d’—ˆ ±=‘Š5œˆ ± œˆ2ˆ=‡ŽŒf¸‹ŽªºŠ–-œ³ ±=‡t´×Œf‹Žˆ±=‡‰[®F‹tŒU’—‹t©ª«œ–UÊU»º§=o®t‹Žª—³=o‡Ž­ÀÂ6’—–  ™Lü ÿŽ˜#µÕæ*§=o–’Ô¦ Š5‡‰––’—©ª«¸®t‹Žª—³=œ–‡Ž© ‹Ž’—ˆ œ±Ö©0¬ÎŠ‘ŒU³=‹t’—‡‰ˆÎ‡Ž­JÈ ‹tŒŽâ~´fštµ—š 0› ´fštµ—Šš #› ´fštµ ™Ž™L›!´‚™Lµ ÿŽ˜#› ´‚™Lµ û ›!´‚™Lµ #µ¸Ñ.­Ò§=@Š ´×®F‹Žª—³ 2’”–}±=‘¿ˆ=œ±°‹Ž–¾ò(ÇS    ™Lü ÿŽ˜‰ÊU› § ’—–k’—–kœÞ#³ ‹ŽªL-‡:™Lµ Ý µ漋t¯Ž$Ë󇎩 ‹Ž’—ˆ œ±@©0¬2‹:ວ=‡‰ª—œ–-¯0¬2±=œ“V‡‰@Š5‡‰–’—’«‡‰ˆ‡Ž­ ‡ o˜ ‰‹ µ ¶¾‡Ž© ‹Ž’—ˆ  Í | ÃÏÇ  ™Lü u™ Ý û™Lü ˜t™Lû™L÷ü ÿ‰Ê$‹Žˆ ±ÐÍÈ | ÃÏÇ  štü #û  ™Lü Ý 0û  štü ÿt™ÊUµ*æ §=œˆ §=À–’«¦Š5‡‰––’—©ª«º®F‹Žª”³=œ–k‡Ž© ‹Ž’—ˆ œ±¸©#¬Š5‘Œf³=‹t’«‡‰ˆ¸‡Ž­ ÈÐÍ ‹tŒfŽâ!´fštµ ˜ Ý ›#´fštµ ˜Lšt›#´‚™Lµ ÿŽ˜#› ´‚™Lµ  Ý ›k´‚™Lµ Ý ˜#›k´‚™L÷µ ÿ‰ÊU»Ó§ ’—–:ª—œ‹Ž± –¾-‡°‹dŠ=´×®t‹Žª—³=~‡Ž­ ™Lµ ûsû ›± ’ 5‘Œœˆ0:­DŒ‡‰ § (¿ Œf– ‡‰ˆ=Žµkæ §0³–¼’—H’”–¼“‘ª—œ‹tŒk§ ‹tk­S‡ŽŒ‹J¨‰’«®Žœˆ2®t‹Žª—³=º‡Ž­Èó¹Óº“‘‹Žˆ¸¿ˆ ±± ’ 5‘ŒœˆHŠ=´×®t‹Žª—³=œ– ­S‡ŽŒ2± ’ 5‘Œœˆ0:-Œf‹Žˆ –­S‡ŽŒf(‹t’«‡‰ˆ –‘µo¶i¸‹œ¬Ý“V‡‰ˆ ú œ“V³=Œf~§ ‹t2’—ˆÎ@‡‰–-–f’«³ ‹t’«‡‰ˆ –œ› §=¾-œ–-–*‡Ž© ‹Ž’—ˆ=œ±o¹Ó‡‰³ ª—±o§‹œ®Ž:V¦=‹Ž“Vª«¬ÝÇD‡ŽŒ*‹tŠ ŠŒ‡œ¦=’—¸‹t-œª«¬ ʐ§=:–f‹Ž@¾Š5‡

(32) ¹Ó‘Œœµ ^U_. ªtžhWj gBrqrugBhmv/«3¬Mruog$qt ¬Mh§v­7e§t dfeL®§rjv/j r¯Mj&iMln¬HkmglRj bdfeWghWiMj]³ gBkmt lžt-qŠµ. æ §=À‹t©5‡O®ŽÀŒœ–f³ ª«–Ò‹tŒfÀ’—ˆ~‹tŠ Š‹tŒœˆ0“V‡‰ˆ0-Œf‹Ž± ’—“V’—‡‰ˆ(¹*’—§¸§=ÀŒœ–³ ª«Ò‡Ž­H4Àœ‹Žˆi‹Žˆ ± ý -‡¹ ý 6k‘Œf± ³ “‘“‘’¾Ç šœÿŽÿt™Ê@¹*§ ’—“U§Õ–‹t-œ±Û§ ‹t¸ª—’—ˆ œ‹tŒ-ŒU‹Žˆ –-­D‡ŽŒf¸‹t’«‡‰ˆ –­DŒ‡‰ã¹ Š Œœ–-‘Œ®L’—ˆ=¨2V¦=“f§ ‹Žˆ ¨Žœ‹t©’—ª—’«z¬i¹‘Œ}‡Ž­H§=:­S‡ŽŒfdâ à !ò. Û ü›„ ý Œþ ß ‰‹. û. ¹*§=‘ŒÒò°~€ ý µ¼æ*§=± ’5‘Œœˆ “VÒ’”–'§ ‹t § œ–-¸‹t-ŒU’—“Vœ–;Š Œfœ–-‘Œ®ŽV¦=“f§ ‹Žˆ ¨Žœ‹t©’—ª—’«z¬ ¹*§ ‹t-‘®Ž‘Œ}§=2± ’—–--ŒU’«©³=’«‡‰ˆd‡Ž­ÒÈ(»'¹Ó2§ ‹œ®Ž¸–§ ‡

(33) ¹*ˆN§ ‹t$§=2–-‘$‡Ž­-Œf‹Žˆ –-­D‡ŽŒf¸‹F´ ’«‡‰ˆ –¹*§’—“f§iŠ Œfœ–-‘Œ®Ž¾V¦=“f§ ‹Žˆ ¨Žœ‹t©’—ª—’«z¬~¹À§=œˆoÈ̒—–ˆ=‡ŽŒf¸‹Žª ’—–ª—‹tŒ¨Ž‘Œœµ 4Jœ‹Žˆ ‹Žˆ 1 ± 6k‘Œf±³ “‘“‘’ Ç šœÿŽÿt™Ê}’—ˆ²§=œ’—Œ¾“V‡ŽŒ‡‰ª—ª—‹tŒ¬Õštµ—š@§ ‹œ®Ž~“f§ ‹tŒf‹Ž“V-‘ŒU’«·‘œ±Ý§= .

(34) HAL author manuscript. —ª ’—ˆ=œ‹tŒ¾-ŒU‹Žˆ –-­D‡ŽŒf¸‹t’«‡‰ˆ –¾¹*§ ’—“U§Š Œœ–-‘Œf®Ž¸V¦L“U§ ‹Žˆ=¨Žœ‹t©’”ª—’«‚¬Žµ7¶(Œf‘Š Œ‡L± ³ “V¸§=‘Œ §=œ’«Œ*’—¸Š‡ŽŒf‹ŽˆºŒœ–³ª«‘â ý Èn,è¹ ¼ '$)DÇ+ɊÇË)+ÍÇËÉYÇ[ÑuÎËÒ]%ÆfÓfÇ!Ð ¿(À±Áf ¡ Á]Ã

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(37) ”ò ò ~€ ý Þ§%Æ$ÏYÊË,)(Ç[%ÎËÒHÃКtû‘ü‘ü‘üFû [Þ¨#×*ÙÉ{%Æy½ìx˜#×̘%sȔ)+*:Ñ5֔åw#; à  Ú Ò]ÇË)DÇÀ ÉË%sȔ*“É“Ê+Õ*“ÆfӘȖÒ]DZÊË, œŠ, Ú *–ÆfÓ9Î[,ÆEÏ*–È”*-,Æ´ÉR* ÊȖҴÇW)[ÉËÈPÎ., Å à›Ì@Æ©, Ê¨#mÎ.,ÆÈn%*–Æ´ÉRȖҴÇ}Ï*ÙÉ+РȔ*“Æ$ÎÈYÇ Å ÇËÌyÇËÆȖÉ!. ú û‘ü‘ü‘ü

(38) û#". Ú *”È–Ò5Ì@à ŠȔ*' Å *”Ί*–È”*nÇ+É$. Ã. ú û‘ü‘ü‘ü

(39) û%$&""ÖnÉË,È–Ò]%sÈ Ö å. $. Ã. æ Œ½'Þ. ȖÒ]ÇËÆȖÒ]ǧ # Î[, Å à]ÌcÆ ÉR, Ê( # Î.,Æ´É+*ÙÉËÈP, ÊíȖÒ]ǧ # ½ *)+$ æ EÏ*ÙÉËȔ*“ÆEÎŠÈ '´ÇË)+Ì@à]Èn%Ȕ*”,Æ É. inserm-00262035, version 1. , ÊØȖÒ]ÇW).É+ÈíÎ., Å à]Ì@Æ$é. 㼋tŒf’—“‘³ ª—‹tŒ¼“‘‹Ž–-œ–!‹tŒfÒ‡Ž© ‹Ž’—ˆ œ±}©0¬}–-‹tŒf’—ˆ=¨ ¹*’—§}§=Ò­D‡ŽŒf z Ü ¨‰’«®Žœˆ:’—ˆ:æ §=‘‡ŽŒœ š¸‹Žˆ ±“f§ ‡0‡‰–’”ˆ=¨o­S‡ŽŒ:§=@Œ‡

(40) ¹À–}‡Ž­ Ü Š5‘Œf³ ‹t’«‡‰ˆ –$‡Ž­Ó§=¸®Žœ“V-‡ŽŒ7Ç štû™Lû‘ü‘ü‘ütû™Êµ Ñzè­ ½à § ’—–}¨‰’«®Žœ–‹Žª—ªÒ§=¸-Œf‹Žˆ –­S‡ŽŒf(‹t’«‡‰ˆ –¾©³=¾­D‡ŽŒ–-‡‰@¥ ½-,ߐ§ (“‘ª—‹Ž–– ¨‰’«®Žœˆ ©#¬æ §=‘‡ŽŒœ ˜d’—–¾ª”‹tŒ¨Ž‘Œœ»H§ ‹t’”–¾’«­º¹~‹Ž“‘“V‘Š ‹Mª«‡‰––¾‡Ž­± ’”@œˆ –’«‡‰ˆ;›;¹ § ‹œ®Ži‹d¨ŽŒœ‹t-‘Œ@“U§=‡‰’—“V(­D‡ŽŒ:§ œ–-(-Œf‹Žˆ–-­S‡ŽŒU¸‹t’«‡‰ˆ –‹Žˆ ±Ý§ ’”–¾¸‹t¯Žœ–’«¾Š5‡‰––’«©ª« -‡N“V‡‰ˆ –--ŒU³ “V:³ –-‘­É³ ª¼Š5‘Œf³=‹t’«‡‰ˆ-œ–-–‹Ž–}¹Ó¸¹*’—ª”ª¼–‘~’—ˆ‹d–f¸‹Žª—ªHV¦=‹Ž@Šª«¸’—ˆ –-œ“V’«‡‰ˆ #µ ÑzÓ’—–Þ#³ ’«-*“‘ª—œ‹tŒ§ ‹tא ·¨¸›#§=*–-‘‡Ž­'-Œf‹Žˆ –-­D‡ŽŒf¸‹t’«‡‰ˆ–kŠ Œœ–-‘Œf®#’—ˆ ¨}V¦L“U§ ‹Žˆ=¨ŽV´ ‹t©’—ª—’«z¬Ž›=’—–º–¸‹Žª—ª«‘Œº§ ‹Žˆ ·¨¸ Ÿ µØ=‡ŽŒ*’—ˆ–-‹Žˆ “V$§=}-Œf’—‹Žˆ ¨‰³ ª—‹tŒ¸‹t-Œf’Ô¦~‡Ž© ‹Ž’—ˆ=œ±i©#¬ ວ=‡‰ª«œ–-¯#¬¸±=œ“V‡‰@Š5‡‰–’—’«‡‰ˆ(‡Ž­;‹Žˆ7V¦=“f§ ‹Žˆ ¨Žœ‹t©ª«}¸‹t-Œf’Ô¦(’”–’—¥ˆ ·¨¸ Ÿ ©³=Óˆ=‡ŽÓ’”yˆ ·¨¸µ ^U_/.. ªtžhWj gBr1qsrgh§v/« ¬HruogEqtn¬Mhmv©­emt dfeò®§rjv/j r¯MjpqeWjp®íj rfo10qsgEqtn¬Mh ²§tžvqsrut k0Wqst ¬Mhÿ¬M«ØvqgEqt vqt d´v. Óà ‡‰ˆ –’—± ‘Œ!‹J–-‹t’—–-’—“Ò ÃóżÇÉÈ@ÊUµHÑz­ Èْ—–!V¦=“f§ ‹Žˆ=¨Žœ‹t©ª«º¹º“‘‹Žˆ2‹tŠ Šª«¬$§=ÓŠ5‘Œf³=´ ‹t’«‡‰ˆ2± ’—–--Œf’—©³=’«‡‰ˆJ‡Ž­LÂ:»tÂ֐‹t¯Žœ–¼§=Ò®t‹Žª—³=œ–kżÇÉò æ È ôÔõ ÷ Ê5¹*’—§¾œÞ#³ ‹Žª‰Š Œf‡Ž©‹t©’—ª—’—’«œ– ­S‡ŽŒH§=׏ OŠ5‡‰––f’«©ª«kŠ5‘Œf³=‹t’«‡‰ˆ¸‹t-Œf’—“Vœ–Hò æ µàӇ‰ˆ –’”±=‘Œ¼ª”’—ˆ=œ‹tŒ -ŒU‹Žˆ –-­D‡ŽŒf¸‹t’«‡‰ˆ – ÿ.

(41) HAL author manuscript. Š Œœ–-‘Œ®L’—ˆ=¨oV¦=“f§‹Žˆ=¨Žœ‹t©’—ª—’—‚¬ÄÍÈ ÃîÛ²È~µ7¶7“‘‹Žˆ ¹ Œf’«-2Â̋Ž–‹M­D³ ˆ“V’«‡‰ˆ°‡Ž­°(ÍÈ â  ÃóżÇÉȸÊkà ÅHÍ Ç 2ÍÈ ÊUµkæ § ºÞ#³=œ–-’—‡‰ˆ¸’—–¼-‡¾¿ˆ ±§=*-Œf‹Žˆ –-­D‡ŽŒf¸‹t’«‡‰ˆ–H­S‡ŽŒk¹*§’—“f§2§= ± ’—–--Œf’—©³=’«‡‰ˆ –J‡Ž­Ó ©‹Ž–-œ±‡‰ˆÝ§ (Š5‘Œf³=‹t’«‡‰ˆ‡Ž­È ‹Žˆ ±‡Ž­ ÍÈ ‹tŒ¸§ (–‹Ž@Žµ Ñz@’—–2“‘ª«œ‹tŒ@§ ‹t˜ Ûa³–-2© Žx½–’”ˆ “V~§ ‘ŒiV¦L’—–2–‡‰@7Â9¹*§ ’—“U§Î‹t¯Ž  ± ’ 5‘ŒœˆJ®t‹Žª—³=œ–À¹*§=œˆ²È9’—–ÀŠ‘ŒU³=-œ±;µÀØ=Œ‡‰ æ § ‘‡ŽŒœ ˜(’«$“‘‹Žˆ²©5–-‘œˆ²§ ‹t §={ "x°-Œf‹Žˆ –­S‡ŽŒf(‹t’«‡‰ˆ – ³ –-©5}‡Ž­H§=}­D‡ŽŒf Û. Ã>zòÌþ!ò ‰‹ û. inserm-00262035, version 1. ¹*§=‘Œ²òô~ò€ ý ‹Žˆ ±z ~ò¹ ý µÐàӇ‰ˆ0®Ž‘Œf–-œª«¬Ö§=œ–N-Œf‹Žˆ–-­S‡ŽŒU¸‹t’«‡‰ˆ –(Š Œœ–-‘Œ®Ž §=M± ’—–-Œf’«©³=’—‡‰ˆÝ‡Ž­$‹Žˆ¬Û–-‹t’—–’—“tµÛæ ‡ –‘o§ ‹t‘›º¹d§ ‹

(42) ®Žd¿ Œf–@-‡ ±=‘¿ˆ=i§= -Œf‹Žˆ –-­D‡ŽŒf@œ±o­D‡ŽŒfo» ’— ’—– Å3Í 2 Ç65'ÊÃóÅP ÷þ — ú ò}|Ç65  8È27 Ê

(43) ×ü 4. ÑzM’”–iœ‹Ž–’—ª«¬½®Ž‘Œf’«¿ œ± ÇDŒfœ@œ:©5‘Œf’”ˆ=¨Û§ ‹tMò | ò à ‡ Ê7§‹t Å Í 4 2 Ç 2ÍÈ Ê Ã Å¼ÇÉÈ@ÊUµ •L’—¸’—ª”‹tŒfª«¬Ž›L³ –’—ˆ=¨2§=:­D‹Ž“V §‹t §=¾Š5‘Œf³=‹t’«‡‰ˆd(‹t-Œf’—“Vœ–Š5‘Œf³=-Ž› ¹Ó¾‡Ž© ‹Ž’—ˆ § ‹t:­D‡ŽŒ:‹Žˆ0¬°ò ú ~&€ ý › 3Å Í 4 2 ÇÉò ú 2ÍÈ Ê}ÃÆżÇÉò ú È2ÊUµ7æ § ’—–}–f§=‡

(44) ¹*–:§ ‹t¾§=(®F‹Žª—³ œ–}‡Ž­ ‡Ž© ‹Ž’—ˆ œ±d©#¬7Š5‘Œf³=‹t’«‡‰ˆd‡Ž­È ‡ŽŒ Æ ÍÈ ‹tŒ¾§=–‹Ž@Ž›‹Žˆ ±d‡L“‘“‘³=Œf’—ˆ ¨@¹*’«§o§= –‹Ž@¾Š Œf‡Ž©‹t©’—ª—’—‚¬Mš «µ †*‡Ž-º§ ‹t¼§=œ–--Œf‹Žˆ –-­D‡ŽŒf¸‹t’—‡‰ˆ –!(‹œ¬¾©5‡Ž­ ŒU‹Žˆ=}¯ (‡ŽPŒ   štµH†À‡Ž-Ó‹Žª—–‡*§ ‹t Å Í 4 2 Ç.ü ʨŽœˆ ‘Œf‹Žª—ª«¬@±=‘Š5œˆ ± –Ò‡‰ˆ È~7 µkÑ.Ó’—–’—ˆ0-‘Œœ–-’—ˆ=¨§=‘ŒÀ-‡±=‘¿ˆ=¥ ø-“‘ª«œ‹Žˆ ù:­D‡ŽŒf¸–‘µ ñó­D‡ŽŒf Åd’”–Ó“‘ª—œ‹Žˆo’«­!9Å ‰‹ à ™‡ŽŒœÞ#³ ’«®t‹Žª«œˆ0ª«¬7:Å ÀÇ ‡} ‰‹ ÊkÃóÅ µÒæ § ’”–ÒŠ Œf‡ŽŠ‘Œf‚¬ –’—@Šª”’«¿ œ–¼§=*–-³±=¬‡Ž­'©5‡Ž§¸“V‡‰ˆ0®Žœˆ0’«‡‰ˆ ‹ŽªHÇɱ=R 0Ž‡‰ˆ ¨=›šœÿŽÿt™ÊҋŽˆ ±@Š5‘Œf³=‹t’«‡‰ˆ ‹Žª Çɖ-‘–-œ“V’—‡‰ˆ =µ ˜‰Ê± ’”–--Œf’«©³ ’«‡‰ˆ –‡Ž­HÞ#³ ‹Ž±=Œf‹t’—“$­D‡ŽŒf¸–*’—ˆiŠ‹tŒ’—“‘³ª—‹tŒœµHÑz­kŲ’—–“‘ª«œ‹Žˆ §=œˆ:’«;“‘‹Žˆ©5–-‘œˆ¾§‹t 3Å Í 4 2 6Ç 55Êà Å!-Ç þ — ú ò | 5'ÊUû

(45) ˆ=‡Ž¼±=‘Š5œˆ ± ’—ˆ=¨Ó‡‰; ˆ È~7 µ Ñ.­Å’—–;ˆ=‡Ž “‘ª«œ‹Žˆ7¹$“‘‹Žˆi“V‡‰ˆ –’—±=‘Œ§=$“‘ª«œ‹Žˆ7®Ž‘Œf–’«‡‰ˆ~‡Ž­¼Å âÒ=Å <×Ç.ü Êà Å ºÇ ‡R ‰‹ ÊVÇ.ü ÊUµºàӇ‰ˆ –’—± ‘Œ ‹¸ª—’—ˆ=œ‹tŒ­D‡ŽŒf6żÇÉÈ@Ê à > | È(»=¹Ó:±=‘¿ˆ }§=¾“‘ª«œ‹Žˆo®Ž‘Œf–f’«‡‰ˆi? <ÃÙ@Å <×ÇÉÈ2ÊA à >(< | È(› š‘™.

(46) HAL author manuscript inserm-00262035, version 1. ¹*’«§B>(< ÃÏÇ ‡R ‰‹ ÊC> µæ*§=œˆ@Â?< ÃÚÂ7D> | È(7 »L–’—ˆ “VÀ§=$–-œ“V‡‰ˆ ±~-‘Œf ’”–“V‡‰ˆ –‹Žˆ ³ ˆ ±=‘Œ'Š5‘Œf³=‹t’«‡‰ˆ}‡Ž­LÈ~›O§=–‹t’—–-’—“‘–5Â֋Žˆ ±J < ª«œ‹Ž±}-‡*§=–‹Ž@Š5‘Œf³=‹t’«‡‰ˆ -œ–-‘µ ØH’—ˆ ‹Žª—ª«¬~’«­ ¹Ó¾±=œˆ=‡Ž-؏ ·!E$§=¾–‘‡Ž­¼ª—’”ˆ=œ‹tŒº-Œf‹Žˆ –-­D‡ŽŒf¸‹t’«‡‰ˆ–º¹*§ ’—“U§iŠ Œœ–-‘Œ®Ž §=:± ’—–-Œf’«©³=’—‡‰ˆ(¹Ó¾§ ‹œ®Ž§=¾­D‡‰ª—ª«‡O¹*’—ˆ=¨2’—ˆ “‘ª—³–’«‡‰ˆ –‘P⠑ Gý F ·!E F ·¨¸ F ·¨¸ Ÿ µ 4Jœ‹ŽˆN‹Žˆ © ± 6k‘Œf± ³ “‘“‘’!–§=‡

(47) ¹Óœ±d§‹tÀ‹¸ˆ=œ“Vœ–f–‹tŒ¬o‹Žˆ ±d– ³ (“‘’«œˆ0*“V‡‰ˆ ± ’«’—‡‰ˆi­S‡ŽŒ ‹¸-Œf‹Žˆ –­S‡ŽŒf(‹t’«‡‰5ˆ Û[‡Ž­ ¹ ý -¥‡ ¹y¼:›¹*’«§ ½ ¾äk›-‡(Š Œœ–‘Œ®Ž:V¦=“f§ ‹Žˆ ¨Žœ‹t©’—ª—’«z¬ ¹Ó‹Ž–º§ ‹t­D‡ŽŒºœ‹Ž“f§oŠ5‘Œf³=‹t’«‡‰ˆi¸‹t-ŒU’Ô¦~ò ú ~€ ¼ ›L‡‰ˆ=}“‘‹Žˆi¿ˆ ±7‹Š5‘Œf³=‹t’«‡‰ˆ ¸‹t-Œf’Ô¦oò Ÿ ~©€ ý –³ “f§d§ ‹t ò úÛ > à ۰ò Ÿ ü ^U_ H. I1j$hWj rgl×qsrgh§v/« ¬HruogEqtn¬Mhmv9­emt dfe>®§rjv/j r¯Mjj´bWdue§gBh§iHj gBkmtžl tnqŠµ. æ §=y4Jœ‹ŽˆÕ‹Žˆ ±6k‘Œf± ³“‘“‘’Ò“V‡‰ˆ ± ’—’«‡‰ˆ“‘‹Žˆ ©5@V¦L-œˆ ±=œ± -‡Nˆ=‡‰ˆL´‚ª”’—ˆ=œ‹tŒ}-Œf‹Žˆ –­S‡ŽŒ-´ ¸‹t’«‡‰ˆ –‘µkñڐ-Œf‹Žˆ –-­D‡ŽŒf¸‹t’—‡‰yˆ 2@Ç.µ ÊŠ Œœ–-‘Œf®Žœ–kV¦L“U§ ‹Žˆ=¨Žœ‹t©’”ª—’«‚¬2‡Ž­5È ¹À§ ‹t-‘®Ž‘Œ’«– ± ’—–--Œf’—©³=’«‡‰ˆ7’«­!‹Žˆ±o‡‰ˆ ª«¬i’«­ ­D‡ŽŒ œ‹Ž“U§Nò ú ~€ ¼ §=‘Œ}V¦=’—–- ò Ÿ ~€ ý –f³ “f§o§‹t ò Kú J ÇÉȸÊà J ÇÉò Ÿ È@ÊUü æ §=M– ³ (“‘’«œˆ “V¬Õ‡Ž­}§ ’—–¸“V‡‰ˆ± ’«’«‡‰ˆß’”–¸–’—@Šª«o-‡ Š Œf‡

(48) ®ŽŽâ°ò ú J ÇÉȸÊià J ÇÉò Ÿ È2ÊU› ò Ÿ È § ‹Ž–Ґ§=*–‹Ž@J± ’—–--ŒU’«©³=’«‡‰ˆ‹Ž–ÓÈ(›0§0³ – J ÇÉò Ÿ È2ʧ ‹Ž–§=À–‹Ž@À±’—–--Œf’«©³=’«‡‰ˆ ‹Ž– J ÇÉȸÊUµ9æ §#³ –7­S‡ŽŒM‹Žª”ª}ò ú ~K€ ¼ ›}ò Lú J ÇÉȸÊ7§ ‹Ž–i§ Ý–‹Ž@ ± ’”–--Œf’«©³ ’«‡‰ˆ‹Ž– J ÇÉȸʹÀ§ ’—“f§7’—–Ӑ§=$±=‘¿ˆ ’—’«‡‰ˆ¸‡Ž­!V¦L“U§ ‹Žˆ=¨Žœ‹t©’—ª”’«‚¬ŽµÑ.­;¹Ó$¹Ó‹Žˆ0 J Ç.ü ʐ-‡2Š Œœ–-‘Œ®Ž V¦L“U§ ‹Žˆ=¨Žœ‹t©’—ª”’«‚¬¹*§‹t-‘®Ž‘Œ§=~± ’—–--Œf’—©³=’«‡‰ˆ²‡Ž­È(›¼§=(“V‡‰ˆ± ’«’«‡‰ˆÝ’”–:ˆ=œ“Vœ––f‹tŒ¬ ‹Žˆ ± §’—–¾“‘‹ŽˆÎ©~Š Œ‡O®Žœ± ©#¬Ý“f§=‡#‡‰–’—ˆ ¨M‹M–-Š5œ“‘’«¿“¸± ’—–--ŒU’«©³=’«‡‰ˆ;›'¹*’«§Ý§ ~–‹Ž@ Œœ‹Ž–-‡‰ˆ ’—ˆ ¨¸‹Ž–*’—ˆ 4Jœ‹ŽˆM‹Žˆ± 6k‘Œf± ³ “‘“‘’×µ ¶;‘N  M$¸7§=¾–-‘ ‡Ž­H-Œf‹Žˆ–-­S‡ŽŒU¸‹t’«‡‰ˆ –º¹*§’—“f§oŠŒœ–-‘Œ®Ž}V¦=“f§ ‹Žˆ ¨Žœ‹t©’—ª—’«z¬Žµ O Á]ûà ¢ ‹ M ¸ *“É É+Èn%uÔ Å Ç9Ô!Õ8%ÏÏs*–È”*-,Ə%Æ$ρÎ.,ÌR'],/É+*–È”*-,Æ šŽš.

(49) ;‘ J ú › J Ÿ ©œª—‡‰ˆ=¨(-‡PM ¸ „ fý „ ¼ ›§=–f³=©–-‘À‡Ž­-Œf‹Žˆ –-­D‡ŽŒf¸‹t’—‡‰ˆ –*­DŒ‡‰ñ¹ ý -‡ ¹ ¼ ¹À§ ’—“f§ÖŠŒœ–-‘Œ®ŽoV¦=“f§ ‹Žˆ ¨Žœ‹t©’—ª—’«z¬Žµßñ*ŠŠª«¬L’—ˆ=¨²§=o¨Žœˆ=‘Œf‹ŽªY4Jœ‹ŽˆL´n6k‘ŒU± ³ “‘“‘’ “V‡‰ˆ ± ’«’«‡‰ˆ;›Ó­D‡ŽŒ7œ‹Ž“f§ ò ú §=‘ŒN³ –-~©5M‹Îò Ÿ –³“f§Ú§ ‹t~ò ú Ç Jú  J Ÿ ÊVÇÉÈ@ÊiÃ Ç Jú  J}Ÿ ÊVÇÉò Ÿ È@ÊUµæ §’—–J­S‡‰ª—ª—‡

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A time-varying respiratory elastance model is developed with a negative elastic component (E demand ), to describe the driving pressure generated during a patient initiated

TIMELY FUNGICIDE APPLICATION: A STRATEGY TO MINIMIZE FUSARIUM HEAD BLIGHT AND ASSOCIATED MYCOTOXIN PRODUCTION IN WINTER WHEAT

The aim of this study was to assess, in three experimental fields representative of the various topoclimatological zones of Luxembourg, the impact of timing of fungicide

'Nature never did betray / The heart that loved her' : l'éthique du retour à la nature dans l’œuvre de Mary Shelley

Attention to a relation ontology [...] refocuses security discourses to better reflect and appreciate three forms of interconnection that are not sufficiently attended to