Work increases the incidence of carpal tunnel syndrome in the general population.
Texte intégral
(2) HAL author manuscript.
(3)
(4)
(5) "!#$&%('*) +%-,.( +/0 123 4 4+ %56$)7%8 28. Muscle & Nerve 2008;:epub ahead of print. HAL author manuscript. 9 :; <=>?A@(;BDCE@F2;4GIHKJMLNGPO*CEQSRT;+FVUDW;MXYCGIHZJ\[GIH]C+F2UD;4^VO_R`FaUN<SQSUbW; c";BbU8;+F^VO*CdTe&GIHKJMLNGPf@(UbBDB8C+@hgi; j UDk4>lBDC <2G HZJ1LNG-mnB8;+oUp<qJr;A<kCEQSRCG HZJ\sG-m#WWT;EQNQt;Yuv;kBD;F2kG cwRJ\sGwfx@e1=nCUDg\y(;ACz@(G HKJMLNG H]C+Fk;AB fn>&BDd y;FV{GTHZJ\sGT|vBDB;W\}2g\y;FVW>WG HKJ~[. inserm-00256944, version 1. \L uvC4y&>&FC Qp>&UF;dh|vFV{>W>grU;;EQ0dh|PUDd g U>lBD>{lU8;;+WCWQt Cz@wF2CE:CU8BDG\}h= GrWU:(;+F<2UQ2 dhmnW {;+F<2GOvXnmnW {;F<2G ^\mnW {(;+F<2G F2CWk; [Jr C+FpQt;gr;WQC+WQt wF2CE:&CUbBG}2Wl<SQVUQN@Qd;:&;UDB8B;<2CWUQtCUF2;}tW ¡2G\^V w¢lCUbWQt^pH]Cz@FaUkA;4G F2CWTk; sw}Nj0A|6=_H£GTY¤l¥`¦GhC+UDWAQt^pH£CE@F2UDk;G ^V w§G F2CWk; 0¨ E.r©Y++ªCQQSFtUy`@QtCEyB8;F2U<V«¬k4C+FVCB QN@WW;B<VeWd F2>gi;T¬T;+U8d;grUD>BD>&{U8kCBh<S@FV:;UB8BCWTkA;¬AY>&Ft«h¬ Y>&FV«T^F2;+BCEQt;d O*>&FtF2;A<VT>&WTd;+Wk;_Qp>-®+cFV>¯2°A9:;<-=x>l?A@(;B8CE@F2;A¬T;^VgiCUbB®±9: =x>?A@(;B8CE@F;²kR@(^VC+W {(;+F< °¯NF UDWCWTkUCBJrUN<2kBD> <S@F2;\ QtC Qt;gr;WAQ ® wRU<wF2;<2;C+FkRi<QN@(dAe\YCA<P<S@>&FQt;4dye#QSRT;_F2;WkRjiCEQtUD>WCB }VW<QtUQN@Qt;_¯S>F-c@yBbU8k_XY;CBQtR1 @F:;UBDB8CWk;}VW<QtUQN@Qd;* \;UDBDB;\CWUQtCUDF2;+¡-rUQSR> @QC+W eYk>&Ft> F2C Qt; <V>Wl<>&F ° ³q2\ ~
(6) + l.7/´r´µµ-E¶(8 2 +ªqmh|·GPCEQ8QSFVUy@QtCEyBD;¯NF2CkzQVUD>WZ>l¯F2UN<V«]Cgr>W {¸QSRT;;+o>h<2;d ;+F<>&W<z¬¹qH}2G y>d eºgiCT<<]UbWd;+o¬0OP}V»¼ ½h¾¿l¢À k4>&W¯SU8d;WTk;ÁUDWAQt;F:CBN¬O_*G´k4C+FVCB QN@WW;B <VeWTd F2>lgr; ¬|6J\Â~G;BD;kEQSFt>d UC{lWT>7<SQSUDk ¬Ã}Nj´ |6|*GF2;+WTkRÄjiCEQtUD>&WTCB}VWh<QtUQN@ Qt;º>¯ QtC QSU8<QtUDk <CWd |·k>&WT>&grU8k\ QN@(d UD;A<z¬=*=GF2;BDCEQtU:;F2UN<V«.
(7) ,(' . HAL author manuscript inserm-00256944, version 1. #! 'ªmnW;+U8d;gU>lBD>{lU8kCBW;EQNY>&Ft«£YCA<1<2;zQ#@UDW]CF2;WkR]F2;+{UD>&WQS>;A<QSUDgiCEQt;´QSR; UDWkUd;WTkA;0>¯O*_ZUbWQSRT; {;W;F2CB> @hBCEQVU>&WZCkk4>&F2dUDW {ÃQS>;+g\BD>&eTgi;WQ\<SQtC QN@< °wO*CA<2;A<~>¯O** >kkE@FVFVUDW`{ÁUDW(CEQSUD;WAQ2< C+{h;4d § Qp> ¢`BDU:(UDW{ÁUDW QtR;H]CUDW; uv>lUF2;]F2;+{UD>lWY;+F2;UDWkB@(d;d F2>h<V;kQSU:;Bbe]¯SF2>lg §§ KQt>£§§ (°"H£;dUDkCBCWd>kkE@CzQSUD>&WRUN<SQt>&FeZrC<\{CEQSR;+F;d ye]giCUDB8;Ad ?A@(;A<SQSUD>&WWCUF; °_}2WTkU8d;Wk4;£F2CzQt;A<0>¯1O*_ C+WTdF2;B8CEQSU:;KF2UN<V«<0p=q=¡0>¯1O** Y;+F2;k4>lg\ @Qt;dUW F2;BDCEQtUD>W´Qt>K;g\lB>&egi;WAQn<QtCzQN@<z°IRT;1CEQQ FVUy @QtCEyB8;1¯FCkEQSU>&Wh<n>¯*F2Up<t«Z>l¯qO_*Qt> ~> FV«ZC+gr>W {ÃQSR; ;EoT>7<;d£;F<2>Wl<iVmh|P¡\Y;+F2;ÃkCBDkE@(B8CEQt;dh°6m Qp>AQtC+B>¯´GV¤l¥ZC QSU;WQ2<ia¥Kr>gr;WGq gr;W ¡ Y;+F2;UDWkB@(d;ddA@F2UbW{ QSRT;£QSR F;;^eT;C+F;+F2UD>dh°nIR;gr;4CWUDWkU8d;Wk;F2CEQt;]>¯0O_*;+FGD§§§ ;+F<>&WT^e;4C+F<wrC<PRU{R;+F6UbWi;grlB>&e;drk>g\C+F2;d#Qt>#@W;grBD>&e;4d;+F<>&W<v+°¦~:(<z°`§h°¥\UDW\r>lgY;AW C+WTd§h°¤ :h< °§h°0UbWg ;W`¡z°IRT; ;Eo&k; <<qF2Up<t«Ã>¯*O*_´YCA<n<QtCEQSU<SQVUkCBBbeZ<2UD{lWUD¯VU8kCWAQ*¯S>FgYCB8;ip=*= ° ¡*C+WTd ¯t;g CB8;\p=* = Kh°§ ¡yB@7;^Vk>BDB8C+FY>&FV«;F<*CWd1¯t;giCB8;\BD>T;+FP{F2Cd;rRUQt;^Vk4>lBDBCFr>FV«;+F< p=* = °¢¡z°TIRT;Ym(|Qt>r> FV«1UDWr{;W;+F2CBlYCA<P¦ À Vl¢À OP}2Gh^a¢¡PUDW\Y>lgr;Wh°mh|<6F2;4CAkRT;Ad RUD{lRT;+Fw:CB@(;A<6UbWi¯V;giCB8;xyB@7;^Vk4>&BDB8C+F-Y>&FV«;F<6V¤¦ À
(8) 8¤l¢`^V¤l¥ ¡6C+WTdBD> Y;+Fw{F2Cd;#<;+F:U8k;A<G7<CB8; <6CWd kBD;+F2U8kCB-rRUQt;^tk>&BDB8C+F*r>FV«;+F<qt¤-z À
(9) S¢`¦^V¤ p¡ °hwR;\m(| UDWgiCB8;yB@(;^Vk>lBDB8C+FPY>&FV«;F<PrC<q¦¤&À
(10) N¦ ^a¥`§ 2°}VW1k4>&WTkB@<2UD>lWGlQSRT;<QN@(d e0<2R> <·C#RUD{lRT;+F*UbWTkUd;WTkA;~>&¯6O**´UDWQSRT;r>FV«UDW {1> @(BDCEQtUD>lW k>g\C+F2;4d~Qp>#QSR;W>W^Nr>FV«UDW {r> @BDCEQtUD>&W(°.
(11) O*C+FVCB´QN@WWT;BZ<VeWd F2>lgY; VO*_¡U8<Ck>lgrgr>lW kBDUDWlU8kCBÃF2> yBD;g QSRCEQ]¯NF2;?A@(;WQSBe F;?A@(UF2; < <@Ft{;+FVeh° [\c> @B8CEQSUD>W<QN@(dUD; <rRC4:&;F2;+>FpQt;dCWWA@(CBUDWkU8dl;Wk4; FCEQt;A<\y;zQNr;;W]§h°¢ C+WTd ¢°N0;+F GD§§§¯S>&FxO_*Ãd;+¯SUDW;Ad´yeZ;B8;kEQSFt>R eh<2UD>lB>&{U8kCB6k+F2UQt;+F2U8C+s ¾ CWd´y(;EQNY;;+W§h° ÃCWd°¢1;+FiGb§§§ ¯S>F<@Ft{lUDkCB1F2;BD;CA<; >l¯´QSRT; gi;d&U8CW WT;+FV:; °DL ¾ L ¼ m#BQVRT>T@{R WT>TQ¸kCE@<2;4d >&WBe yeY>&FV«G1O** F2;+F;A<2;+WQ2<0Cg C 2>F1F2>> FNQSUD>W>l¯iCBbBnF2;+{UN<Qt;+F;d>&FMk>&g~;W<2CEQtCzyB;¸Y>FV«^F2;BDCEQt;4dd UN<;C <2;A<0UW giCW eÃk> @WAQSFtUD; <z° ¾ » lUDWk; giCW e>l¯wQSR;UDWdU:(U8dA@(CB-F2U<t«¯VC4kEQt> F<q>¯*O*_C+F2;B8; <<qgr>d&U8¯VU8C+yB;\QSRCW Y>&FV«BCk;¯tCkEQt>F<2GUDW¯S>&F2giCEQSUD>W C+y> @QQSRT;UDWkU8d;Wk;]>l¯1O**UbWQSRT; Y>&Ft«UbW`{ > @hBCEQVU>&W U< ;A<<2;WAQtUDCBlQt>#QtC+FV{;Qw`F2;E:;WQSUD>&Wi;¯S¯S>&FQ2< °ji;E:;+FSQSR;B8;A<z<2Ghd;<VUQt;#UQ2<w:CB@(;#¯NF2>g C @yBU8kR;CBQSR:U8;+ >UbWQtG_BDUQNQSBD;ÃUDW¯S>&F2giCEQtUD>&W]UN<iC+:CUB8C+yB8;¸>WKQSR;FVU8<V«>¯\O**CQQSFVUy`@QtCEyB8;Qp>£~>FV«¯SCkEQt>F<rUDWKQSR; {;+WT;+F2CB>& @(BDCEQtUD>Wh° ¾ LVL ¾ L wR; F2;WkR }aW<QtUQN@Qt; ¯S>&Fc@yBU8k XY;CBQtR @F:&;U8BB8CWk; QSR;+F;¯S>F2; UgrB8;gi;WAQt;4d C+Wi;+U8d;giUD>lBD>{Uk4CB<@FV:;UBDB8CWk;\<Veh<Q;g ¯S>FPO** UDWYQSRT;{;WT;+F2CBh> @hBDCzQSUD>&Wi>l¯QSR; H]CUDW;C+WTd~uv>UF2;pH \u6¡wF2;+{UD>WrUbW ; <Qt^VO*;+WQSF2C+BF2C+WTkA;UDW\§§ ° wR;1CUg >&¯PQSR; F2;<2;WAQn<QN@(dAe0iCA<qQt>KCA<<2;A<<QSR;1UWTkU8d;Wk;1>¯O**KCk4k>&Fd UbW`{Qt>K;+g\BD>&egi;WAQ <QtCQN@<6C+WTd#QSR;Ft>&T>&FNQSUD>Wr>&¯kC<2; <6CEQ8QSFVUy @QtCEyB8;_QS>\~>&Ft«\UDW#QSR;{;+WT;+F2CB>& @(BDCEQtUD>Wr>&¯hQSRT;F2;+{UD>Wh° . HAL author manuscript. . . . inserm-00256944, version 1. . . . + 2 5v+ 2
(12) 4 %. w R;0>& @BDCzQVUD>WUDWkB@(d;4d£UDW¸QSRUN<1<SQN@(dAe]k>lg~FaUN<;dKF2;A<2U8d;WAQ2<Y>&¯QSRT; H \uF2;+{UD>lW y;zQNr;;W#QSRT;C+{;A<6>¯§^a¢`
(13) G¦¤#~>gr;Wra¢`§h°NzÀ¡6C+WTd G¥`§ \gi;Wrh° À0¡ ° @y 2;kEQ2<1rRT> RCd @(Wd;+Ft{>&WT;;B;4kEQSFV>d U8C+{W>h<QSUDk]p|6J\Ân¡¸<SQN@(d&U;A<Ã>¯ QSR; @;+FBDUg\y<yeQSRT; ¯VU:(;´<;WQVUDWT;B6R eh<2U8kUCWh<n>¯PQSR;1>&WBeZ¯S> @Fn;B;kEQSF2>d UDC+{W>h<QSUDk1k4;WQt;+F<n>¯PQSR; H ruF2;{lUD>WYY;+F2;n;BUD{Uy(B8;#¯S>FIQSRT;Y<SQN@(dTeiUD¯-QSR;+eY;F2;F2;A<2UDd;WAQ2<v>¯ QSRT;\d;¯UDW;d {;>{F2C+RU8knC+F2;C`° WBbe kC<2; <>¯ O** rUQSRT>T@QFtUD>&F RUN<Qt>Fe >l¯ O*_ >¯QSR; <Cgi; ~F2UN<QY;+F2;ÄUDWkB@(d;Ad F2>h<V;kQSU:;BbeÃy&;EQNr;4;W§§ KCWTd §§ °}VWTkU8d;WAQxkC<2;A<n>¯O** Y;+F2;1d;¯SUDW;d yeÃy> QSRÃkBDUDWlU8kCB C+WTd;B8;kEQSF2>R e<2UD>lBD>{Uk4CBxk+F2UQt;+F2UDC´@<2UDW{£QSRT;K<2Cgi; <SQtC+WdCF2d&U ;4d£F2>AQp>lk>BDG·~RU8kR]¯S>lBDBD> r;4d QSR;.
(14)
(15) . .
(16) "!$#!&%'
(17) . (. ). &*.
(18) @yBUN<2RT;d F2;k>lgrgi;WdCEQtUD>Wh<z° ¼ w> y&; UDWTkB@(d;dG <Vegr Qt>&gi< RTCd Qt> y&; kBCA<z<2UD¯VU8;d C < kBDC <<2U8k F2>Ty&C+yB; O*_ Ckk4>&F2d UDW`{ Qt> QSRT; k>&W<2;Wl<S@-< k+F2UQt;+F2U8C ¯S>F O*_ kBDC <<2U¯tUk4CEQVU>&W UW ;+UDd;g UD>BD>&{U8kCB_<SQN@(d&U;T<GNL[nC+WdÃCEQqBD;4CT<SQPQN~>Ã>&¯PQSRT; ¯S>lBDBD>TYUbW{|6J\ k+F2UQt;+F2UDCY;+F2; F2;4?A@hUF;d®-+z¡ d;BDC+e0UDWQSR;~d&UN<QtCBhgY>TQt>FBCEQt;Wk+eM>l¯ QSRT;Ygi;dU8CW W;F:;npJ\HZu6¡PN@;+FPBU8g UQI>l¯wW>F2grCBDGh°¤ g <t¡z¬ ¡id;k+F;CA<2;ÃUDW<;Wh<>&FSe]k>WdA@7kEQSUD>W£:(;BD>kUQSe>&¯QSR;Ãg ;4d&U8CWW;F:;ZCA<z<2;A<z<;d]>&FQSRT>ldFV>grU8kCBBe y;zQNr;;WrQSR;QSR@hg\yGlQSRUFd1d&U{UQvC+WTd\F2UN<QvSBD>TY;+F*BDUgiUQv>&¯6W>FVgrCB8Gh§ g V<V¡z¬(V ¡PF;+BDCEQtU:;\d;B8C+e0UW <2;W<2>Fe£d&UN<SQtCBqBDCEQt;+Wk+e£>l¯QSRT;¸gr;4d&U8CWWT;+FV:;Ãk>lg~hC+F;d YUQSRKQSR;´@(BbWTC+FrW;+FV:&;¸CzQQSR; QSR]d&U {lUQ p@;+FvBbUDgiUQ6>l¯wWT>&F2grCBDG(§h°¢rg1<t¡E¬&¡Pd;4k+F2;CA<;\UbWMCgBUQN@(d;#>l¯QSR;#gi;dU8CW´<2;W<2>FeiWT;+FV:;nCAkzQSUD>lW >AQt;+WQSUDCBp<j mc¡CEQ\QSRT; QSR@hg\y CWd QSRU F2d dU{UQBD> r;FBDUbgiUQ0>¯1W>F2grCBDG´§ l n¡¬nCWd a¢¡ CEyWT>&F2grCBUQVU8;A<n>¯·QSRT; F2;k+FS@hUQtgr;WAQqCEQ8Qt;+FVWÃ>¯PQSR;1CEy(dA@(kzQS>F>BbBDU8kUyF;4:UN<ng\@-<kB;1dA@F2UDW {ZW;;dBN; ;BD;kEQSF>&g\eT>&{FC+lR e(° |·CkR0;B8U{UyB;\CEQtUD;WAQ6YCA<UDW¯S>&F2gi;d0>l¯wQSR; <SQN@(dTe1ye QSR;R eh<2U8kU8CW CWTd <2UD{lWT;d Cnk>Wl<;WAQ"¯S>&Ftg C¯Qt;+FwQSR;nkBbUDWU8kCBCWd W;z@F2>&R e(<2UD>lBD>{Ukn;+oCgrUDWCEQVU>&Wh< ° H];4d&U8kCB6RUp<SQt>&FSeGwUDWkB@(dUDW{F2UD>FRUp<SQt>&FSe>l¯qO_*G-RCWdK<Vegr Qt>g <2GwCWd´QSRT;1k>&WTkB@<2U>lW>W´QSR; |6J\º<QN@(d eM>l¯-QSR;rg ;4d&U8CW1W;+FV:&;a<V¡PY;+F2;#F;+>&FNQt;dQp>1>T@FPB8C+y>F2CQS>Fe(°lmnBQtR> @{RQSR;#|6J\º<QN@(de YCA<<2UgiUB8C+F¯S>FqCBbB6<@y ;kEQ2<2Gd;EQtC+UDB8;d |J~ºdCEQtC#Y;+F2;rCE:CU8BC+yB8;¯S>Fq>&WBe]GD§ Ã<@y ;kEQ2<qt§ À¡ Vk> FtF2;A<V>WdUDW {´Qp>椴C+WTd¸¢`¦kC<2;A<x>&¯·O_*ÃC¯¯t;kEQSUDW {´QSRT;F2U{RAQqCWdBD;¯QP~FaU8<QtG-F2;A<t;kEQSU:(;BDe ¡ ° >FQSR;1>AQSRT;+Fn+§ À >¯kCA<;<V¡2G6>&WBDeQSR;0k>WkB@<2UD>lWÃ>¯_QSR;|6J~ <QN@(d e´YC <\C+:&CU8B8C4yB8; °m <2;B8¯S^ CdgrUbWUN<Qt;+F;d?A@(;<QtUD>&WWTCUF2; YCA<\QSRT;W]giCUB8;dKQt>;+C4k+R<S@ly ;kzQ°}VW¯S>FVgrCEQtUD>WKrC <ik>BbB8;kzQt;d>W gi;dUk4CBZCWd <@Ft{lUDkCBÃRUN<Qt>Fe V>Ty&;A<2UQSeGÃdUC+y&;EQt;A<gr;BB8UQN@<2G´QSR e`F2>lUd d&UN<2;4CT<;G{&eTW;k>lB>&{UDkCAB RUN<Qt>FeTG´\F2UN<Q RCWd QSF2Cz@g C4G F2UD>FO**lGÃC+WTd @l;FBDU8gYy g\@<2kE@(BD> <t«;B;zQtCB d&UN<2>F2d;+F<V¡CWd ;g\BD>&egi;WAQ"UDWdA@<QSFeTG>lk4kE@CEQSUD>WGC+Wdrd;A<kFaU QVUD>Wi>&¯hQtCA<t«h<6dA@FVUDW {\QSRT;F2;k;dUDW{1¢#eT;C+F<V¡ ° wR; F2;A<t>&W<2;F2CzQt;·QS>QSR;?A@(;A<SQSUD>&WWTCUbF;_rCA<I¦ À° @(CBDUQSe k>WAQSF2>BP>¯QSR;0dCEQtC rC<#;Fa¯S>F2gr;dK¯S>F´4§§£<S@ly ;kzQ2<#FC+Wd>lgrBDe<;B8;kEQt;4dKUbWç§ CWd UDWAQt;+FV:U8;EY;d yeQt;BD;lRT>&W;¤gr>WAQSR<ÃBCzQt;+Fz°w>C<<2; <<0QSR;>h<<2UyU8BUQSe >l¯´UDWkB@<2UD>lW yU8CA<GCB8B . HAL author manuscript. . inserm-00256944, version 1 . .
(19) . #. # .
(20) !
(21) .
(22) ! # !. (. (. (.
(23) . (.
(24) HAL author manuscript. CEQSUD;WQ2<UDWkB@(d;dUDW\QSR;\<QN@(dAeiUDWr§§ \r;+F;k>lg\CF2;d#rUQSR\CEQtUD;WAQ2<6RC+:UDW{\@hWTd;+FV{>W;#<@Ft{lU8kCB F2;BD;C <;\>&¯-QSRT;\gr;dUCW1WT;+FV:;\UDW §§ ^§§@<2UDW{ QSR;\gr;4d&U8kCB-¯SUB8; <*>¯-QSR;nm#W`{h;+F<XYCWTd1O*;WQt;+F2G ~RUkR0;+F2¯S>&F2gr;4dC+y> @Qq¦§ À >&¯*UDWAQt;+FS:;WAQtUD>Wh<¯S>&Fn<@FV{UDkCBwF2;B8;C <2;i>l¯QSRT; g ;4d&U8CWW;F:(; UDW QSR; H ruZF2;+{UD>&W(°. inserm-00256944, version 1. %.(N wR;ÃkRC+F2CkEQt;FVUN<QSU8kA<M>&¯#QSRT;{;W;F2CB> @hBDCzQVUD>W]>l¯#QSRT;´H Yu F2;+{UD>lWKY;+F2;K;+o`QSF2CkEQt;d¯NF2>lg QSR; F2;WTkR j CEQtUD>WCB0}aW<QtUQN@Qt; >¯] QtC QSUN<QSUkT<£CWTdÁ|*k>W>gU8k QN@(dUD;A<]} j´ |6|P¡]k;Wl<@<£>l¯h° }VWTkU8d;Wk4;#F2CEQt;A<6r;F2;r;A<QtUDg CzQt;dye1CEQtUD;WAQvCWTd WT>TQye ~FaUN<SQtG"<>QSRCEQv;4Ck+R (CEQSU8;WAQwrUQSR yUbB8CEQt;F2CAB O*_ÃrCA<nF2;{C+F2d;dZCA<~>&WT;´kC<2; °wwR;0dCEQt;0>&¯*QSR; |6J~ <QN@(dAeYCA<@-<;d Qt>Zd;+¯SUbW; QSR;0dCEQt;0>&¯ dUDC+{W>h<2Up<q>¯*O**lGhy;k4CE@<;#QSR;rdCEQt;r>&¯wQSR;r>Wl<;EQ*> ¯q<Veg Qt>g <PYC <UDgrF2;kUN<;r>&F*W>AQ·CE:&CUDB8C+yBN; ¯S>F6CEy> @Q§ À >&¯kC<;A<z° m{;^qCWTd´{;+WTdl;+F^a<V;kUD¯VU8k CWW@(CB6UDWkUd;WTk;F2CzQt;A<_Y;+F2;ik>g\ @Qt;d ~UQSR1QSR;W@hg\y(;+Fx>&¯v;+F<2>Wh< <@(¯S¯V;+F2UDW {¯SF2>lg O** WT;+rBedUC{lWT>7<;ddA@F2UbW{ QSRT;e;C+F0@Wd;+FÃk4>&Wh<2UDd;+F2CzQSUD>&W C <ÃWA@(g ;F2CEQt> Fz° mr<<@(g UDW{\QSRCzQhQSR;{;+W;F2CB>& @(BDCEQtUD>W\F2;giCUDW;d <SQtCEyB8;GTQSRT;d;+W>gUDWCEQt>F-YCA<6C+Wr;<QtUbgiCEQt;>¯hQSR; CE:&;+F2C+{;\WA@(g\y(;+Fv>&¯w;+F<2>W^e;CF<*>¯-QSR;\<Cg ;nC+{;\CWTd{(;WTd;+FvdA@FaUDW`{ QSR;\<Cgi;;+F2UD>dyC <2;di>lW QSR; }Nj´ |6| k4;+Wl<S@-< dCEQtC ° ÃwR;C+{;4^VCd @-<SQt;d F2;BDCEQtU:;F2UN<V«<ÃN=_=q¡Ã>¯0O_*ÁUDW Y>&Ft«UbW{ <@y ;kEQ2<ndA@F2UDW {QSRT;Me&;C+Fn>¯dU8C+{W>h<2Up<Gk4>&g\CF2;d´Qt>¸WT>&WT^pr> Ft«UbW`{<S@ly ;kEQ2<dA@FaUDW`{ QSRT;Me&;C+Fn>l¯ dUDC+{W>h<2Up<G7Y;+F2;rk>lg~ @Qt;d´C4kk>F2d UDW {1Qt> ~>&Ft«´UDW1{(;+W;+FCB"CWd Qt> ~>&Ft«´UDWÃ<V;kUD¯VU8k UDWdA@<QSFeCWd >kkE@CQSUD>&W]k4CEQt;+{>FVUD;A<\@<2UDW{KQSR;´H£CWQt;BD^pXYC;Wh< ;Bgr;EQSRT>ld¯S>Fr;CkRK{;WTd;+Fz°6IRT;ÃCEQNQNFVUy`@QtCEyBN; ¯NF2CkEQSUD>Wi>l¯-F2UN<V«1UDWM;4oT>7<;d UDWdU:hU8dA@(CBN<*Vmh|
(25) À S¡-rCA<vk>g\ @Qt;dYQp>1;A<NQSUDg CzQt;xQSRT;F2>>FNQSUD>&Wi>l¯ kCA<;A<6>l¯O** CQQSFVUy`@QtCEyB8;_QS>Y~>FV«#@<tUDW {\QSR;¯S>lBDBD> rUW`{ ¯S>Fagn@hB8C®DL . . . (. (. *.
(26)
(27)
(28)
(29). ! .
(30) . QtC QSU8<QtUDkCBhCWTCBDeh<;A<r;+F;;+F2¯S>&FVgY;d#@<2UbW{0 cv¸°§ <t>¯QNrC+F; °. .
(31) ~)h%D. HAL author manuscript inserm-00256944, version 1. m tQ >AQtC+Bx>&¯G¤l¥£kCA<;A<Ma¥£Y>&gi;WG gr;Wh¬qgiCB8;®¯t;giCB8;ÃF2CEQtUD> `®±°¢¡2Gk>FF2;<V>WdUbW`{Qt> GD¤ ´~FVUN<Q2<xC¯S¯t;kEQt;d ye¸O_*G r;F2; UDWkB@(d;ddA@F2UDW {´QSRT; ^e;CF;+F2UD>dh° ;E ;BDUD{Uy(B8;(CEQSU8;WAQ2< F2;+¯@<2;4dMQt>¸<tU{W QSR;rk>Wh<2;WAQv¯S>&F2grG-gYCUDWBbe0y;k4CE@-<; >¯PB8Ck+«>&¯wQtUbgi; °(IRT;+F2;#YCT<*WT>´F2;k4>&F2d UDW`{>l¯ QSR;F;+¯@-<CBp<GTy`@QhQSR;;<QSUDgiCEQt;{lU:&;W\yenQSR;#<;WQVUDWT;B(R eh<2U8kUCWh<-YCA<6B8;A<z<-QSRTC+W§ À° O*_0C¯S¯V;kzQt;dQSR;#F2U{RAQtGBD;¯QtG>&Fy&>AQSR~F2Up<SQ2<*UDW1§ ÀÃGhÀÃGC+Wd1l¥À >¯vkC <2;A<G7F;A<V(;kEQtU:;Bbe(°& >&F y> QSR0{;+Wd;+F<G<Veg Qt>g <*i;+F2;ikBC<z<2Uk1O**¸UDWÃC+y&>T@Q¥`§ À >¯*kC <2; <¯S>F_y&>TQSR1~FaUN<SQ2<z°wR; giCUW |6J\ k+FVUQt;+F2UDC_@<;d#Qt>rd;+¯UDW;drO**YY;+F2;Cd;BDC+eiUDW#QSR;_JnHu >&¯hQSR;gi;dUCW\W;F:;GCd;k+F;CA<2;UW QSR;<;+Wh<2>Fe k>WdA@(kEQtUD>W :&;BD>lkUQSeTG#CWTdgr>F2;KF2C+F;+Be Cd;k+F2;4CA<2;UDWQSR;j mc Cg\lB8UQN@(d; °*m\W UDWk+F2;C <;>¯wQSR;gY;d&U8CW w@(BbWTC+FB8CEQt;Wk+ed&UD¯V¯t;+F2;WTk;YYCA<qBD; <<q¯NF2;?A@7;WQy&;kCE@<;#QSRUp<qgi;CA<S@F2;#rC < ;+FV¯S>F2gr;dr>WBberUDWikCA<;>l¯-grUB8drO*_iV6CEyBD; z¡z° wR;?A@(CBDUQek>&WQSF2>B>&¯hQSR;dCzQtC¯S>&F§§\F2C+WTd>&grBDe´<;BD;4kEQt;d <@y ;kEQ2<P<2RT>TY;d\W>rUbW¯S>F2giCEQSUD>WYyU8C < y;zQNr;;W QSRT; <;B¯S^2CdgUDWUN<Qt;+F2;4dÁ?A@(;A<SQVU>&WWTCUDF2;CWdQSR;UDWQt;+F:U8;E F2;{C+F2dUbW`{Á{;WTdl;+FG C+{;Gi> F ;g\BD>&egi;WAQ<SQtC QN@< °O*>&g~C+F2Up<>&W >l¯M-kC <;A<U8WkB@(d;d UDW §§ rUQSRQSRT;§§ CWd§§l gi;dUk4CB1¯SUB8; <Z>¯ QSRT;mnW {;+F<XYCWdO*;WQt;+F<VRT>TY;d QSRCEQCEy&>T@`Qä§ À >¯ QSRT;k4CA<2; <Z>¯O** @Wd;FV{>lUDW {<S@FV{;+FVeKY;+F2;W> QnUDd;WAQtUD¯VU8;dKye]> @F\W;EQN~>FV«h°ji>d UD¯S¯V;+F;WTk; iC<r¯S>T@(WdKy;EQNY;;W QSR;<2; <>T@Fk;A<qF2;+{C+F2dUDW {ÃC{h;G-{;Wd;+F2Gw;g\BD>&egi;WAQ<SQtC QN@<G->FBDC <Q_>lkkz@C QSUD>Wh°wR;rF2>> FpQSUD>Wh< >¯<@y ;kEQ2<wY>&FV«UDW {1UDWQSRT;#giCWA@(¯VCkzQN@FVUDW {GhC+{F2U8kE@(BQS@F2;Ghk>Wl<SQSF@(kQSUD>&WTGhC+WTd´<2;+FV:U8k;#UDWdA@<QSFVUD; <vdUd W> Qvd UD¯V¯t;+FPy;EQNY;;W QSR;A<;#QNr><2> @F2k4;A<z°(IRT;YFt>>FpQ UD>lW0>¯yB@(;^Vk>lBDB8C+FPY>&FV«;zF<qC+WTd´BD> r;F_{FCd; ~RUQt;^Vk>BbB8C+F-Y>FV«;+F<-YCA<wUDW#QSRT;#<2Cgr;>F2d;+F">&¯grC+{WUQN@(d;¯S>F-y>AQSRi<2> @F2k;A< ° H];4d&U8kCBwCWTd¸<@FV{U8kCBwRUN<Qt>FeCWd0;grBD>&egi;WAQq<QtCEQ8@<Pr;F2;r>&WBDeÃC+:CU8BC+yB8;¯S>FPQSR; ¥¢ Y>lgr;W C+WTd §rgr;W#rRT> k>g\B;zQt;dQSR;?A@(;<QtUD>&W`WCUF2; °H;+W
(32) Ngr;CWrC+{;h°r J h°¢¡e`F< wCWd#Y>&gY;AW
(33) Ngr;CWC+{;K° J h° ¡re Fz< ´<@(¯¯t;+F2UDW { ¯SF2>g¿Oq_Y;+F2;KF2;+BCEQVU:&;BDee> @(W { V6CEyB8;K¡z°· ;E UDWkUd;WQ6kCA<;A<v>l¯wO**Y;+F2;nd&UDC{lWT>7<;d dA@F2UDW {iF2;+{WCWTk4eMÀ¡PC+WTd C+y> @Q6À >&¯r>gi;W C{;Ad y;zQNr;;W§^eT;C+F<RCd@<;d >F2C+Brk4>&WQSF2Ck;+ QSU:(;A<z°wR;F2;+:CB8;Wk;]>l¯M>Ty&;T<2UQe p¹*H} l§ . (. (.
(34) «{ SgN¡YCA<q<2Ug UDB8C+FPy;zQNr;;W1g ;WMCWTdr>gr;W1+¤ À¡ °IRT;#F2;E:&CB;WTk;\>l¯6dUDC+y;EQt;<*g ;B8BbUQN@-<6rC < ÀÃGlrUQSRT>T@`Qvd&UD¯S¯V;F2;Wk;\y;EQNY;;+W1{;Wd;F<z°RT;YF;E:CB8;Wk;\>l¯-QSR eTF2>lUDd1dUN<;CA<;YC <*RUb{R0>WBe UW Y>&gr;Wr À¡z°h@FpQSRT;+F2G§ À >¯-gi;+WrCWTd§ À >¯hi>gr;WRTCdr>Ty&;A<2UQSeGd&U8C+y;zQt;A<6gr;BBUQN@<2GCWTd S>F QSR e`F2>UDd dUN<;CA<2;4G&QSR;nC+{;^VC4d @<Qt;4dF2;E:&CBD;Wk;#UDWk+F2;C <2UDW {0<2UD{lWU8¯VU8kCWAQtBeiUDW1k4CT<;#>¯ @(W;grBD>&egi;WAQ Vl¥À :h< °h¢ÀK¬ c §h°§§-z¡°qIRT;£F2;z:CB8;Wk4;>¯ QSR;A<;dUN<2>F2d;+F<d UDd WT>TQi:C+FVe<2UD{WUD¯VU8kCWAQtBbe Ckk4>&F2d UDW`{YQp>UDWdA@<SQSFVer>F>lkkz@CEQSUD>WrkCEQt;+{> FtUD; <z° wR;KkF@(d;KC+:;F2C+{;z^Vgr>WAQSRUDWkU8d;WTk;K>¯ O**>T:&;+FQSRT;K^eT;C+Fi;+F2UD>ldrCA< °±¯S>FKGD§§§ ;+F<>&WT^e;4C+F<6UDWYY>lgi;WrCWdr§h°¤¯S>FGD§§§Y;F<t>&WT^te&;C+F<6UDWrgi;W(° 6R;UbWkU8d;Wk;>¯-O** UDWr§§ G §§G-CWd1§§ YC <r°¢`G*°¤G-C+WTd£° C+Wd0§h°¤G-§h°¦ GC+Wd0§h°¤´¯S>&FrGD§§§1;+F<2>W^Ne;C+F<UDW1r>lgY;AW C+WTd g ;WTG#F2; <V;kzQVU:;BDeh°xR;]dl;4k+F2;CA<;]>¯´UDWkU8d;Wk4;> yh<;+FV:;d ¯S>F Y>lgr;W UbW §§ rC<ÃW> Q <QtCQSUN<QtUDkCBBDe<2UD{WUb¯tUkCWAQvCWdy> QSR\QSR;\grCB8;®¯t;giCB8;#FCEQSUD>0C+WdQSRT;#F2>>FpQSU>&WM>&¯-Y>&Ft«UbW`{<@y ;kEQ2< dUDd WT>AQw:C+FVe0<2UD{lWUD¯VU8kCWAQtBe1dA@F2UDW{ QSR;n;+F2UD>ldh°}VWTkUDdl;Wk;\UbWTk+F2;C <;drUQtR1C+{;~pc K§h°§§-¡PUDW y> QSR {;+WTd;+F<2GhrRCzQt;E:(;+FPQSR;r;grlBD>egi;WAQq<QtCEQN@<qV6CEyBD;r¡z°hwR;\F2>> FNQSUD>W0>l¯wr>FV«UDW {K<S@ly ;kzQ2<PrC < RUD{lRT;+F*UDW (CEQSU8;WQ2<rUQSR1O*_ QSRTC+W1UDW QSR;#{;W;F2CB > @(BDCEQtUD>&WM>&¯-QSRT;#H Yu]F;+{lU>lW1V§ À :h< w¥zÀ UDWrg ;WrCWTdM¥`§ ÀÄ:< ° ¤¤ À UDW#Y>gr;W ¡z°`IRT;k+F@(d;gi;C+WrUDWkU8d;Wk4;F2CEQt;>¯-O**;FGD§§§#;+F<>&WT^ e;4C+F<YCA<*RU{R;+FPUDWM;grBD>&e&;d;+F<2>Wh<IQSRTCW Cgr>W { QSR>h<2;@W;grBD>&e;4d UbWrQSR;e&;C+FP>¯wdU8C{lWT>7<2UN<
(35) °¤K:h< x§h°¥UDWKY>lgr;W]CWd]§h°¤-1:h< °P§h°§UDWgi;W]py> QSRK c §h°§§-z¡ a°6wR;¸BCEQNQt;+FikCQt;+{>FVe k>g\F2UN<2;d y> QSR´<S@ly ;kEQ2<6rR>1RC4d WT;4:(;Fr>FV«;dGg CUDWBbe Y>lgr;WTG CWTd@hWT;grBD>&e&;d <S@ly ;kzQ2<*UW QSR;eT;ACFK>¯d&U8C+{W>h<2UN<z°\wR; C+{;^VC4d V@<Qt;4d =*= UDWº;g\BD>&e;4d <@y ;kEQ2<Zk>lg~C+F2;d rUQtR QSR>h<2; @W;grBD>&e;4d UDW1QSR;e&;C+F>¯*dU8C+{lWT>7<2U8<_YC < °
(36) Nl¢4À OP}2G*°¤`^° PUbW1Y>lgr;WCWd°
(37) Nl¢À OP}VG §h°^+° -UDWrgr;Wh° wR;;grlB>&e;d<S@ly ;kEQ2<i<@(¯¯t;+F2UDW{¯NF2>g O*_KY;+F2;¸gYCUDWBbe]BD> Y;+F\{F2Cd;1rRUQt;^Vk4>lBDBCF#r>FV«;+F< C+WTdyB@(;^tk>&BDB8C+Frr>FV«;+F<iCWdF2CF2;Be]y(;BD>lW`{;d£QS>]gr>&F;¸?A@(CB8U¯VU8;d]>lk4kE@CEQtUD>&W]k4CEQt;+{>FVUD; <z°vIR; ;Eo&kA;<<6>l¯F2UN<V«i>¯-O**YYCA<P<SQtCEQSUN<QSU8kCBBDe1<2UD{lWUD¯VU8kCWAQ¯t>&Fg CB8;CWdr¯S;giCB8;xyB@(;^tk>lBDB8C+F-r>FV«;+F<6C+Wd ¯t;giCB8;´BD> r;F#{F2C4d; <;+FV:Uk4;A<2G_<CB; <GPCWdKkB8;+F2UDkCB~RUQt;^Vk>BbB8C+FY>&FV«;F<~6CEyB8;´ ¡ °-}VWZk>WAQSF2CA<NQtG . . HAL author manuscript. . inserm-00256944, version 1. (. (. (. . (. (. (.
(38) HAL author manuscript inserm-00256944, version 1. R UD{lRT;+FrB8;4:&;B>kkE@CzQVUD>WkCEQt;{> FVUD; <2G<@(kR]CA<\Y>lgi;+W]k+FC¯Q2<^\CWd<CB8;A<V;F<2>Wh<rCWd]g CWTC+{;+F<G Qt;k+R`WU8kU8CWh<2GC+WTd1C <<2>kU8CEQt;#Ft>&¯S;A<z<2U>lWCBN<*>l¯wy> QSR {;Wd;+F<Glr;+F;\CA<z<2>kUDCEQt;dYUQSR1C\BD> r;FPF2U<V«0>l¯ O*_°}tWQt;+FVg1<>&¯1UDWdA@<SQSFeTGY>FV«UDW {UDW C+{F2Ukz@hBQS@F2;]¯S>F Y>&gY;W`¡2G#giCWA@(¯SCkEQN@FVUDW { ¯S>F1y>AQSR {;+WTd;+F<V¡Gk>Wl<SQSF@(kEQSUD>WÃV¯S>Fg ;W`¡nC+WdG-Qt>KC BD;<z<2;+Fn;Eo`Qt;+WAQtGP<2;F:U8k; UDWdA@<SQSFaU;A<nV¯S>&FY>gr;W ¡YC&< CA<<2>kUCEQt;d£rUQSRCW;4o&k; <<iF2Up<t«>¯rO*_°P}VWk>WAQSFtCA<QtG_~> FV«UDW`{UDWQSRT;£<;+FV:Uk4;KUbWdA@<SQSFVU8;A<rrC < CA<<2>kUCEQt;dKrUQSRC¸BD> r;FF2UN<V«>l¯~O*_¯S>F gr;WV6CEyB8; ¡ °Pm#gr>W {r>lgY;WTG·QSRUN<iBCzQNQt;+F1<2;kEQp> F giCUbWBbe UDW :>B:(;4dyB@(;4^Vk>lBDB8C+F0CWdBD>T;+F1{F2Cd;¸rRUQt;^Vk>lBDB8C+F Y>&Ft«;+F<0a¥À¡¬Cgr>W { gi;WGnUQ UDW :>lB:(;d1yB@;4^Vk>BbB8C+FPY>&Ft«;+F<q À0¡qC+Wd0CB<2>C\F2;BCzQSU:&;BbeBCFV{;\;+F2k;+WQtC+{;r À¡*>¯v?A@(CBDU8¯VU8;Ad ~RUQt;^Vk>BbB8C+F-Y>FV«;+F<6CWd\FV>¯S;A<z<2UD>WCBN<z° wR;nCEQNQNFVUy`@QtCEyB8;Y¯NFCkEQtUD>&WiVmh|P¡vUbWi;grlB>&e;dr;+F<>&W<2G&rRU8kRrF2;+F2;<;WQ2<wQSR;F2>&T>&FNQSUD>Wi>&¯"O_q <V;4kUD¯VU8kCBDBbeZCEQNQ FVUy @QtCEyB8;Qp>Y> FV«ÃCgr>W { kC <2;A<n>kkE@FtFVUDW {ÃUDW´QSR;YY>&Ft«UbW`{Ã>& @(BDCEQtUD>W YCA<¦ À Vl¢À O·}Gw ^a¢¡q¯S>&F*~>&gr;WCWdk> @(BDdW> QPy;ik> gr @Qt;d¯S>&Fqgr;Wh°wR; mh| >&¯*O**F2;CkRT;Ad :CB@(; <n> :;+Fn¤§ À ¯S>&F¯S;giCB8;1CWTd¸giCB8;MyB@7;^Vk>BDBCFY>&Ft«;+F<nC+WTd¸¯S;giCB;1BD> r;F{F2Cd;´<2;F:U8k; <G <2CB8;A<G-CWd0kB;FaUkCB rRUQt;4^Vk>lBDB8C+FPr>FV«;+F<q6CEyB8;r ¡z°}VW Qt;+FVg <q>¯PUDWdA@<QSFeTG7QSRT;\mh|>&¯vO*_1rC < RUD{lRT;+FUDW0C+{F2U8kE@(BQN@F2;rV¯S>&FPY>&gY;W`¡qC+Wd0k>Wh<QSF@(kQSUD>W´UDWdA@<QSFVe ¯S>F*gr;W ¡PQSRCW0UDWgiCW@h¯SCkEQN@FtUbW{ ¯S>F-y>AQSR\{;Wd;+F<t¡6CWd#QSR;#<;+F:U8k;UbWdA@<SQSFVU8;A<6V¯S>F-~>&gr;W`¡6VCzyB;¡ ° ~
(39) 4) 8. wR;£<SQSF2;+W`{ QSR]>&¯QSRUN<<QN@(dAeBU8;A<1UDWQSR;ÃUbWkB@<2UD>lW>&¯\UDWkU8d;WAQYO_*UDW£QSRT;{;WT;+F2CB> @BCzQSUD>lW F2;+> FNQt;dye CM<;WAQtUbWT;B<@FS:(;UDB8BCWk;\WT;EQNr>FV«M>&¯wR e<2U8kU8CWl<qk4>T:&;+F2UbW`{C\B8C+FV{;~C+F2;Cr>¯IQSRT;#F2;+{UD>lW(° O*CA<2;]d;¯UDWUQtUD>lW C+{F2;;4dYUQVR]QSR;k>&Wh<;Wl<@<0d;¯VUDWUQVU>lWl<¯S>&F0;+UDd;gU>lBD>{lU8kCB <S@F:&;UBB8CWk4;>l¯ O*_ »V¾ L[vC+WTd QS>>«ÃUbWQt>KCk4k+> @WAQPQSRT; @yBDUp<2R;4d F;k>g gi;WdCEQtUD>Wl< ¼ ¯S>FW;E@F2>R eh<2U>lBD>{lU8k´<QN@(dUD; < >¯O**° W;1BU8gUQ2CEQSU>&WÃ>¯·QSRT;´<QN@(d e´YC <QSR;1B8Ck+« >&¯q;+oRCE@<SQVU:&;WT; <<n>l¯PQSRT;´<;WQSUDW;B6W;EQNY> FV« ~RUkRB8;d1Qt>¸CW @WTd;+F2;A<SQVUDgiCEQtUD>&W>¯QSR; UDWkU8d;WTk; >¯*O*_°wR; BDCk«Ã>l¯*;+oRCz@<QtU:&;W;A<z<>¯QSR; W;zQNr>FV«k+> @BDd y&;;+oTlB8CUDW;d yedU¯V¯t;+F2;WAQv¯SCkEQS>F< °lwR;rWA@(g\y(;+Fq>&¯6;+F<>&Wh<<S@h¯V¯t;+F2UDW {¯SF2>lg O** . ).
(40) rUQSRT>T@Qn@Wd;FV{>UDW {|J~ <QN@(dUD; <iUp<\@(W «W> ~W£y`@lQ~ Ft>Ty&C+yBeRUD{lR(° }Q~grUD{lRQ#y&; >h<<2UyB8;´QSRCEQ ;g\BD>&e;4d<@y ;kEQ2<\Y>T@BDdy;¸gY>&F2;ÃBUD«;BbeQt>£@WTd;+FV{>K|J~ <SQN@(d UD;A<M>&F1<@Ft{UDkCB*F2;B8;CA<2;´QSRTCAW @W;grBD>&e;4d <S@ly ;kEQ2< °j ;+:;FQSR;B8;A<z<2GlQSRUN<<>T@Fk;\>l¯wyU8CT<*UN<*F2> yC+yBDe0BD>T UbW1F2CWTkA;4G"<2UDWk;rgr>h<Q >¯7QSRT;k>h<Q2<6C+F;C+UDdYyenQSR;\>kUDCB-;kE@F2UQSeTGTYRCEQt;E:&;+F-QSR;;g\BD>&egi;WAQ6<SQtC QN@<6>¯hQSR;CEQSU;WQ2<z° }VW <2>gi;KCEQtUD;WAQ2<2G\<@Ft{lUDk4CBnF2;B8;C <2;>l¯\QSRT;£gi;dU8CWW;+FS:;¸YCT<M;+F2¯S>&F2gr;drUQVRT>T@Qr|6J\ <pQN@(d U8; < dA@F2UDW {QSR; F2;4k;dUbW{ ¤¸gr>WAQSRl< °7XY> r;E:&;+F2G-QSR;+eZg UD{RAQqRC+:;0CWÃ;B8;AkzQSFV>d UDC+{W>h<QSU8k1;+:CB@(CEQtUD>lW ;C+F2BDU8;+Fz°>&F0QSRCEQ0F2;4CA<2>WG1<@FV{UDk4CBMdCEQtCC+Wd |6J\ <SQN@(d UD; <ZC+F2;W> Q;CA<Ve Qt>Ák4>&g\CF2;CEQ1QSR; UDWd&U:(U8dA@(CBB8;+:(;B °l>g ;;4>&B8;BbU:(UDW{ UDW#QSR;H ru CF;CgrUD{RAQRCE:&;_@hWTd;+FV{>W;;B8;kEQSF2>d UDC+{W>h<QSU8k <QN@(d U;T<6UDWiCW CF2;CW> Qwk> :;+F2;4dYye\QSRT;WT;EQNr>FV«i`FV>Ay&C4yBDeiB; <<IQSRTCW ¢À >&¯";BUD{lUyB8;nkC <2;A<t¡z° m ¯t;+ ;BDUb{UyhB8;1kC <;A<F2;¯N@<2;d´Qt>£<tU{W´QSR;1k>Wh<2;WQ¯S>F2g ¯S>F\<2;z:;+F2CB6F2;CA<>&Wh<GgrCUDWlBDeZ¯S>&FnBDCk+«Z>l¯PQSUDgi;° wR;BDCk+«i>&¯;+oRCE@<SQVU:&;WT; <<-YC <6CBp<> dA@(;PQS>#QSR;_@WT;?A@(CBC+FQSUDkUDhCzQSUD>&WY>l¯hQSR;#<2;WAQtUbWT;BlR eh<2U8kU8CW< > :;+FQSRT;QSR F2;;4^teT;C+F;+F2UD>dGgrCUDWBbeZUDWK§§ ° W;1R eh<2U8kU8CWZW> QSUD¯U8;d¸:&;+FVeK¯t;E kAC<2; <n> :;+FQSR; QSR F;;£eT;C+F< CWd CWT>TQSRT;+FBD;¯Q QSRT;W;zQNr>FV« UDW§§ ¯S>&F0;+F<>&WTCBnF2;C<2>Wh°}2W CddUQVU>lWG<>&gi; ;BDUb{UyhB8;nkCA<2; <wr;F2;#W> QwUDWkB@(d;dy;4kACz@<2;n>l¯ QtUDg ;nlF2;<<@F; °h @(k+R F;CA<2>Wh<wr;F2;#CBN<2> F;+>&FNQt;d UDW C <2U8g U8BCF#<;WAQSUDW;BWT;EQNY>&FV«UbW1QSR;YMlmr° xIRT; B8Ck+«Z>¯q;4oRTCE@<QtU:;W; <<n>&¯PQSRT; W;EQNr> Ft«Ã;EoB8CUbW< QSR;\F2;BCzQSU:(;BeBD>T ;A<QtUDg CzQt;>¯PUDWkU8d;Wk;r>l¯vO*_0UDW QSRUp<*{;WT;+F2CB>& @(BDCEQtUD>W0k>&g~hC+F;dMQp>QSR>h<2; F2;k4;+WAQtBe F2;+>FNQt;d UDW QSR; {;WT;+F2CB >& @(BDCEQtUD>Wl< >l¯ O*CWQt;+Fy`@Fe CWd lU;WWC @<2UbW{ ;BD;kEQSF>&R e<2UD>lB>&{U8kCB6d;¯SUDWlUQVUD>W0>l¯PO**°±s ¾ XY>TY;E:&;FG W>Ã<2U{lWUD¯VU8kCWAQ·d&UD¯S¯V;F2;Wk; <PY;+F2;r>Ty<;+FV:;d y;zQNr;;WiCEQSU8;WQ2<*UDWkB@(d;d UDW QSRT;<QN@(d eMCWTdQSR>h<2;QSF;CEQt;d´<S@FV{UDkCBBDe1F2;{C+F2dUbW{0C{;Gh{;WTd;+F*CWd B8C <Q >lk4kE@C QSU>&W(°1O*>&W<2;?A@7;WAQSBeG;+:&;W QSRT>T@{R QSR;UbWTkUd;WTk;Á>¯O*_ºrCA<@WTd;+F2;A<SQVUDgiCEQt;dG ;A<SQSUbgiCEQt;<>l¯vF2;BCzQVU:;rF2Up<t«Z>&¯qO*_ÃC4kk>F2d UDW {Qt>{;EWTd;+F2GwC+{;iCWTdÃ;grBD>&eTg ;WQ<QtCEQN@<*Y>T@BDd´y(; ;EoT;AkzQt;dQS>\y;_@WyUC <;dh° wR; gi;EQSR>d>&B>&{e Y; @<2;d dU8d W>AQCBDBD> F;kUN<2; CA<<;A<z<2gi;WQ>&¯yUD>lgi;kRTCWU8kCB CWd h<VekRT>7<>lk+UCB*F2UN<V«]¯VC4kEQt> F<\¯S>FrO** °6OP>Wl<;?A@(;WAQtBeGPQSR;UDWdA@<SQSFe V>FQSR;>lkkz@CEQSUD>WkCEQt;{>&Fe`¡ YCA<@<2;dZCT<~C F2> oe ¯S>F~;Eo>h<@F2; QS>ÃFVUN<V«¯SCkzQt> F<\¯S>F\O**h°DLLPJn@(;QS> QSRT; <2gYCB8B*WA@(gYy(;F\>l¯ (. (. HAL author manuscript inserm-00256944, version 1. ). . .
(41) @W;grBD>&e;4d CEQtUD;WAQ2<GlQSR;\F2;kUN<2UD>W0>l¯IQSRT;r;A<QSUDgiCEQt; <q>&¯wQSR;rC+{;4^VCd @-<SQt;d =_= C+Wd0mh| >¯PO** UDWi;g~lBD>e;d <@y ;kEQ2<-YCA<wF2;BDCEQtU:;BbeYBD>TM° . (. HAL author manuscript inserm-00256944, version 1. rm <´F;4:U>T@<2BDe F;+>&FSQt;dUDW>& @(BDCEQtUD>W^yC<2;dÁ<SQN@(d U; <GQSR;UDWkU8d;Wk;]>l¯0O*_rCA<RUD{lRT;+FUW Y>&gr;W0CWd1UDWk+F2;C<2;d rUQSR0C+{;\¯S>FPy> QSR {;+WTd;+F<z° s ¾ ;EY;+FQSRTCW À >l¯-Y>lgr;W1UDWkB@(d;d UDW QSR; <QN@(dAe~r;+F;F2;+{WCWAQ"CWd#QSR;F>&>FpQSU>&Wr>¯7Y>lgr;W\@<2UDW {M>&F2CBhk>WAQSFCk;+ QSUD>W#iC<_<2U8grUB8C+FwQS>YQSRTCEQ > yh<2;F:;dUDWQSR;K{;W;F2CB>& @(BDCEQtUD>Wh°DLs1wR;KF;E:(CB;WTk;>l¯rdU8C4y&;EQt;A<1gi;BB8UQN@<0UDWCEQtUD;WAQ2<rrC < QN~UDk;rCA<qRUb{RQSRTCEQvUbW QSRT;#{(;+W;+F2CB>& @(BDCEQtUD>W1>l¯-QSRT; <2Cgi;C{;GNLs*C+WTdMQSRUN<qk>W¯UDF2g1<PQSR;\¯VUDWdUbW{< >¯<S@FV{lU8kCB\<;+F2U;<z°DL ¼ O*>&W<2Ud;FaUDW`{QSRCEQ~W>]F2;+¯S;+F2;Wk;ÃdCEQtCK<QtC+WTdC+F2dU ;d¯S>F1<2;+oCWd]C+{; Y;+F2; CE:&CU8B8C4yB8;¯S>&F-QSRT;{;+W;F2CB>& @(BDCEQtUD>Wr>&¯hQSRT;_H]CUDW; uv>lUF2;F;+{lU>&Wrk4>&WTk;+F2WUDW{ dUDC+y(;EQt;A<6gr;B8BbUQN@-<G Y;1k>T@Bd¸W> Qxk+>g\ @Qt;QSRT; F2;BDCEQtU:&; F2Up<t«Z>l¯qO_*ZCkk>F2d UDW {Qt>Kd UC4y&;EQt;A< ° y; <2UQSe´CA<QNrUDk4;1C&< ¯NF2;?A@7;WAQICA<PUDW\QSR;{;W;+F2CB>& @(BDCEQtUD>Wi>l¯ QSRT;F2;{lUD>W1C{;d¸¢\eT;C+F<P>F6gr>&F;#C+WTdYQSRUN<vC+{F2;; <wrUQtR <@FS:;+eh<*UDW QSR;n{;WT;+F2CB>& @(BDCEQtUD>Wh° [h\W¯S>FQN@WTCEQt;+BeTG7QSR;~CE:CUB8C+yB8;\dCEQtC\>W1> y;<2UQeMUDWQSR;#{;+W;F2CAB > @BDCEQtUD>&W0>¯IQSRUN<xC+F2;Crd>´WT>TQ·C+BDBD> ÄgY>&F2;\F2;4kUN<;iC+WCBe(<UN<x>&¯wQSR;rF2;B8CEQSU:(;YF>&BD;i>&¯·>Ty&;A<2UQSeCWd >kkE@CQSUD>&W]>W¸QSRT;´F2UN<V«]>l¯~O*_°wm#BQVRT>T@{RÃQSR;K<QN@(d e k>&W¯tUbF2gi;d¸QSRT;¸k4>l^V;zoUp<SQt;+Wk4;>l¯ng ;4d&U8kCAB k>WdUQtUD>&W<6«lWT>T~W\Qt> UbWTk+F2;C<;xQSRT;F2U<t«1>l¯"O_*1UDW <>gr;CEQtUD;WAQ2<2GhUQICB<2>´<tR> r;d\QSRCEQICEy> @ QI¦§ À >¯ ¯t;giCB8;CWd ¥`§ À >l¯ giCB8;KCEQtUD;WAQ2<0dU8dW> Q0<@T¯¯t;+F0¯F2>g CW e>l¯\QSR;g1°qRA@<G#gr>h<QMkCA<;&< >kkE@FVF2;4dUDWF2;B8CEQSU:(;BeeT>T@(W { CWTdRT;CBQVR er>FV«UDW{Y>&gi;WCWTdgi;Wh°*wRUp< ;+lU8d;g U>lBD>{lU8kCB F2>¯UDB8;\>¯6O*_1UDWQSRUN<P{;WT;+F2CBh> @hBDCzQVUD>Wid&U8¯V¯t;+F<vd&FCA<QSUDk4CB8BbeM¯F2>g QSRT;YRUN<SQt>&FVUkCBkBUDWlU8kCBF2>¯U8BN; >¯O**lGiCkk>F2d UDW {QS>\RU8kRO*_>lkkz@F<ÃgrCUDWlBDe UDW grU8dd&B8;^tC+{h;4d Y>&gi;W <@(¯S¯V;+F2UDW{ ¯NF2>hg R>F2gr>WCBd&UN<2>F2d;+F<z° »V¾ L ¼ m <S@yh<SQtCWQSUDCBwWA@(g\y(;+Fq>&¯vkCA<2;A<q>kkE@FtF2;d1UbW<S@ly ;kzQ2<BD; <<PQSRCW0§ eT;C+F< >¯ C{;G£FC+UN<2UbW{ k>Wk4;+FVWh<CEy&>T@QQSR;Ä>AQt;WAQSU8CBBD>W { Qt;+FVg ;¯S¯V;kzQ2<>&¯ O** WT>AQ >&WBe >lW g\@<kE@(BD>7<t«;B;zQtCBR;4CBQVR#y`@Q"CB8<2> >Wr;+g~lBD>eg ;WQ° wRUp<<QN@(d e <2RT>Ti<QSRTCEQigr>h<QikC<2;A<0>¯iO*_UDWQSR;¸{;W;F2CB>& @(BDCEQtUD>W>lk4kE@FVF2;dUDWr>FV«UbW{ <@y ;kEQ2<M>&¯\y&>TQSR]{;+Wd;+F<GC+FQSUDkz@hB8C+F2Bbe UbWyB@(;^Vk4>&B8BCFY>&FV«;F<1CWdBD> i;+F {FCd; rRUQt;^Vk>lBDB8C+F . *. ). (. . (. .
(42) Y>&FV«;F<z°A|q<QSUDgiCEQt;A<·>&¯-QSRT;#=_= >l¯6O** r;+F;~y&;EQNY;A;WK°¢iCWd UDW Y>&FV«UDW`{¸<S@ly ;kEQ2<*UDW1{;W;F2CAB C+WTdKQt>]UbW]yB@;4^Vk>BbB8C+F\Y>&Ft«;+F<z°vIRT;A<2;F2; <S@hBQ2<MC+F2;Ãk>Wl<2UN<SQt;+WAQnrUQSR;+UDdl;grUD>lB>&{U8k£<QN@(dUD; < <VRT>TYUbW`{ÁRUD{R;+FUbWkU8d;Wk;F2CEQt;<>¯1O*_UDWk4;+FQtC+UDW>kkE@CzQSUD>&WCB\{F>T@h<G#giCUDWBDeUDWdA@-<SQSFVU8CAB Y>&FV«;F<z° ¾ »t¾ L \m#BDB*QSR;¸giCUDWUDWdA@<SQSFaU;A<\r;F2;¸UDW :>Bb:;4dG;Eo(k; Q\¯S>F1<2;+F:U8k;ÃUDWdA@<QSFVUD; <i¯S>&Frgr;WTG rUQSR1=*=F2CW {UDW{¸¯NF>lg °¥ Qp>h°§l°lX~> r;E:&;+F2G =*=g UD{RAQ*RTC+:;y;4;W1@(Wd;+F2;<QtUbgiCEQt;4d y;k4CE@-<; >l¯ QSR; 4dUB@QVU>&W n>l¯ :&;+FVei;+o>h<2;d <V;4kU8¯VU8kCkEQtU:UQVU8;A<*<V@(k+RYCT<6¯S>>ld\Ft>lk4;A<<2UDW {MCWdrkB;4CWUDW{GCgr>&W{ B8; <<iRUb{RBbe ;+o>h<2;d]>kkE@CEQSUD>Wh<z° ¾ L iwR;F2;A<S@hBQ<0<@>FpQQSRT;Ã>&UDWUD>lWKQSRCzQr>kkE@CEQSU>&WTCBqF2Up<2« ¯tCkEQt>F<\¯S>FrO*_]C+F;k+>Wk4;WQSF2CQt;dKUDW¸Y>&FV«;F<rgr>h<Q~;EoT>7<;d¸QS>F2;+;QSUQtU:&;gr>&:;gi;WAQ2<YCWTd S>F R;4C4:e lR e(<2UkCB Y>&FV«BD>Cdh°rwR; F2U<V« >¯ZO_* CA<z<2>kUDCEQt;dÁ~UQSRÁY>&FV«ºUDWÁQSRT;Á<2;+F:U8k;Á<2;4kEQt>&F d F2CA<SQSUDkCBBDeMd&U8¯¯t;+F2;dy&;EQNY;;W{;WTd;+F<z°TIRUN<6F2> yC+yBbeiF2;¯SB;kEQQSRT;{;Wd;FPdU:Up<2U>lWi>l¯ Y>&Ft« UDW\QSRU< <2;4kEQt> F2G¸<tUbWTk;Ágr><Q >&¯ÃQSR; r>gr;W y;BD>W {;d Qt> QN~>ÄRU{RºF2UN<V« BD> ?A@(CBU¯SU8;dÄ>kkE@CEQSUD>W kCEQt;{>FVUD; <2G \RT;+F2;C<giCW ergi;W\y;BD>lW`{;d#Qt>YRU {lR\{FCd;>lk4kE@C QSU>&Wh<-YUQSRrCBD>T FVUN<V«i>¯-O**° JY;A<VUQt;UQ2<:&CB@(;¯NF2>lgQSR; @yBU8kR;CBQSR:U8;E >lUDWAQtGlBDUQNQSBD;nUbW¯S>F2giCEQVU>&WrUN<vC4:&CUB8C+yB;_Qt>iCA<<;A<z<-QSR; mh| >¯*O*_1QS> ~>FV«G PF;+F2;A<;+WAQtUDW {1QSR;gi;CW1F2>>FpQSUD>W0>¯PO**CEQNQ FVUy @QtCEyB8;YQp> Y> FV«Cgr>&W{ Y>&FV«UDW`{ <@y ;kEQ2<z°P}tW> @F1<QN@(dAeTGCEy> @Qr¦À >¯rkCA<;A<1>¯rO*_UDW£Y>&Ft«UbW`{Y>lgr;Wk4>T@(BDd£y(; CEQ8QSFVUy @Qt;d QS>Á~> FV«°~IRT; <QtCQSUN<QSU8kCB > Y;+F¸YCA<UDWl<S@h¯t¯VU8kU8;WAQ0QS> Ft>T:TUDd; C kBD;4C+Fk>WkB@<2UD>hW F2;+{CF2d&UDW`{ QSRUN<¯NF2C4kEQVU>&W UDWr>FV«UDW { gi;Wh°Xr> r;z:;+F2G UQK<2RT>T@(BDdÁy;y>FVW; UDW giUbWd QSRCzQ´QSR; kCBDkE@(B8CEQtUD>&WY>l¯-mh|]UDW :>lB:&;d#r>FV«rUDW\{;W;+F2CBDGCWTd ;A<SQSUDg CzQt;A<6>l¯mh|KY;+F2;RUD{lRT;+FUDWr>kkE@CzQSUD>lW {F2> @h<w\UQSRi{F2;CEQt;FP;EoT>7<S@F2;Qt>´<2;grUD^F2> @QSUDW;n>&F6F2>A@QSUDW;#giCWA@7CBlY>&FV«°TIR@<2GhO**1kCA<;A<·k> @Bd y;k>&Wh<2U8d;+F;dCA<rCzQNQSFVUy @QtCEyB8; Qt>¸Y> FV«¯S>FrCEy> @ QqQNR`F2;;^V?A@(CFQt;+F<Y>&¯ngrCB8;yB@(;^tk>lBDB8C+F#Y>&FV«;F<2G QN~>^ QSR`UF2dh<q>l¯P¯t;giCB8;yB@7;^Vk>BDBCF_Y>&FV«;F<qC+Wdgr>F2;#QSRCW0RCB¯·>l¯P¯t;giCB8; BD> r;+F*{F2C4d; <2;F:U8k; <G <2CB8;A<·CWTd kB8;+F2U8kCB7YRUQt;^Vk>BbB8C+FwY>&FV«;F<z°A|q<QSUDgiCEQt;n> ¯mh|UDWY>&FV«UDW { Y>&gi;W UDWM>T@F*<QN@(d e\iC < kBD>h<2; Qt>QSRCEQik4C+BDkE@(B8CEQt;dUDWQSR;H]>WAQSF2;CB\<SQN@(dAea¢¢À¡1k>g\C+F2UDW {QSRT;KUDWkU8d;Wk;Z>l¯ <@Ft{lU8kCB F2;BD;C <;>&¯ QSRT;g ;dU8CWWT;+F:(;y;zQNr;;Wg CW@(CBiCWdW>W^VgiCWA@(CB\r>FV«;+F<ÃUbW ^a¢°DL @F ;A<SQSUbgiCEQt;<IY;+F2;CBN<2>ikBD>7<;_Qt>#QSRT>7<;>&¯hQSR;UDF*<QN@(dAe\rRT;WYY;>WBbeMk>Wl<2U8d;+F2;d\yB@(;^Vk>lBDB8C+F-Y>&Ft«;+F< (. HAL author manuscript. . . . . . inserm-00256944, version 1. . . (. . ). .
(43) HAL author manuscript. >¯Iy&>TQSR1{;+WTd;+F< °hwR;B8CEQ8Qt;+FPF2;<@(BQ2<<@{{;A<SQwQSRCEQ6~> FV«^F;+BDCEQt;d1¯tCkEQt> F<*UDWkF2;CA<2;#QSR;\F2U<t«>l¯vO*_G y @Q]gY>&F2;F2;+¯SUbW;4d gi;EQSRT>ld>BD>{&e <2R> @(BDdÄF2> :UDd; gr>F2;ÁF;k+U<; C<<2; <<2g ;WQ>&¯KQSRT; ¯SC4kEQt>&F< UDW :>lB:(;dh°mh| d&UDd1W> Q-QtC«;#UWAQt>0Ckk4>T@WQvC+W eMUbWdU:hU8dA@(CBkRC+F2C4kEQt;+F2U<QtUDk <*>¯-Y>&FV«0CWd W>W^Nr>FV« ;EoT>7<S@F2;r>&F*gr;dU8kCBwRUN<Qt>Fe0CWd QSRA@<qdU8d´W> Q·d; Qt;zF2gUDW;#QSR;rkCz@<2CB-F2;B8CEQtUD>Wl<2RUD´y;zQNr;;W0O** C+WTd~Y>FV«iC QQSR;UDWdU:(U8dA@(CBlB8;+:(;BN°DL. inserm-00256944, version 1. n!
(44) %). |vUDdl;grUD>lB>&{U8kACB*<@FV:;U8BB8CWk;0>&¯xO*_KUDW C {;WT;+F2CB6>& @(BDCEQtUD>WKUDWQSRUp<r<SQN@(dTe<2RT>TY;dÃC1RUb{R;F UDWkUd;WTkA;Z>&¯iO**UDWQSR; Y>&FV«UDW`{> @B8CEQSUD>Wk>grC+F2;d£Qt>QSR;¸WT>&WT^pY>&FV«UDW {> @(BDCEQtUD>&W(°_m <@y<SQtC+WAQtUDCBF2>>&FNQSUD>W1>¯PkC <;A<q>l¯6O*_0dU8C+{lWT>7<;d1UbW QSRT;BD> Y;+FP{F2Cd;#rRUQt;^Vk>BDBCF·Y>FV«;+F*C+Wd yB@(;^Vk>BbB8C+F]r>FV«;+FkCQt;+{> FVUD; <Y;+F2;CEQQSFVUy @QtC+yB8; QS>Ä~>&Ft«h°1m#BQSR> @{R QSR;F2;A<@(BQ2<g#@<SQy; k>W¯U Fagi;dKUDW >TQSRT;+F\CF2;CA<G"QSRT;4e F2>T:U8d;´U8gr>&FNQtC+WAQqWT;E UDWh<2UD{RAQ2<QS>Kgr;4CT<S@F2; QSR;´UDgrCkEQx>&¯xCAW ;Eo&kA;<<wF2UN<V«i>¯-O** UDW#QSR;_Y> FV«UDW {r> @hBCEQVU>&WrCWd#Qt>QtC+FV{;Q F2;z:;WAQtU:;CkEQSU>&W(° !¨Y³. \3 ~', wR; CE@QSRT>&F<QSRCW « J\F<]cwU8;+FVF; uv>&WTkRCgr QtG mnWW; \U8;U8BB8C+FQCWd zCk?A@7;A< ~B8;UDW ¯S>FQSRT;UDF C+FQSUkUDCEQtUD>W UDWQSR;;WQSUDW;Bqj1;EQNY> FV« C+WdJ\F1cU8;+FVF2;K=*@(kC+e¯S>F´RUN<R;BDUbWF2;C+F2UbW{QSR; giCWA@<2k+F2U Q° .
(45) ~!,. ° m F2g UQtC+{;´cwGP¹x;+FVFVef#GPH]CEQNQSRT;Ei<Vj0 °q QtCEQSU<QtUDkCBngr;EQSRT>ldl<iUDWgi;d&U8kCBqF2; <2;C+FkR(° o¯S>F2dG ¹xBDCk+« r;B8B c @yBUN<2RT;+F<2G§§h° ° mQSF2>h<VRU6}2GPf@(ggi;A<z<>&WZO*G >&R`Wh<<2>W=xGP;EQnCBN° cF2;E:&CB8;Wk;0>&¯xkC+FVCBQN@W`W;B<VeWd F2>gr;´UDW]C {;+WT;+F2CB>& @B8CEQSUD>Wh° zmH]mº7¬h¥®N¢`^+¢¥° ).
(46) h° ¹xBDCWdaJncwGl=*@(d>lBD¯S;+F H °lO*BUDWUk4CB6<@F:(;UDBB8CWk;\>¯PkCFVCBlQN@WW;B<VeTWd F2>gr;\UbW QNY>0C+F2;CA<·>&¯ QSRT;_\WUQt;4d ~UDW{d>lgrGw-^§§-°wj ;z@Ft>&Bji;E@F2>h<@FV{\c6<e&kRUCzQSFe\§§h¬ ¦ ®p¤¦ ^+¤¦h° ° JYCE:U8; <uvG ;BB8g CWrXrGlc@WW;EQNQwuq°(T@FS:;UDBB8CWk;\>¯IY>&Ft«^F2;BDCEQt;d1kCFVCBlQN@WW;Bw<VeWd F2>gr;\UW H£CA<z<2CkR@<;EQQ2<G# ^+¦®wC F;+>&FNQ¯NF>&g QSRT; H]C <<2CkRA@<2;zQNQ2< ;+WQSUDW;B6|:(;WAQ·j >AQSUD¯SU8kACzQVUD>W el<SQt;gÁ¯S>F k4kE@CEQSUD>WCB=UN<V«i |"j´ =¡ °Amng P}VWTd~H£;d\§§-¬ ®¢¥`^V¦-° ¢° C4yB8;k«lUO ~GlmnWdC+FVe\H]6G&BD>;EQt;+FwH ~Gh;EQIC+BN°AcF2C4kEQNU8k;C+F2Cgi;EQt;+F®A|vBD;kEQSF>ld UDC{lWT>7<SQSUDk<QN@(d U8; < UDWkC+FVCBQN@WWT;B´<VeWd F>&gi; °=;>&FNQ>&¯1QSR;mngi;F2UDk4CWm\<z<2>kUDCEQtUD>W>&¯1|*B8;kEQSFt>ld U8C+{W>h<QSU8k H£;d&U8kUDW;Gmngi;+F2Uk4CW mnkCd;ge >l¯]j ;E@F>lBD>{&e CWd mng ;FaUkACW mnkCd;ge >¯ c"R eh<2U8kCB H£;d&U8kUDW;C+Wd#=x;RC+yUbB8UQtCEQtUD>Wh°j ;E@F>&BD>{e\§§ ®¢¥(®p¢¥`^+¢` ° ¤h° ~B8;UDW y(CE@(g JYf#G\ @(BbB8U:(CW H]G_¹xC+FV«;+F~jYJM°Pm >k+«;Qr{ @UDd; Qt>;+UDd;grUD>BD>&{e°F2UDW {;+FG ji;E9~>FV«G§§¦l° ¦h° H£k¸C+F2B8CWT;Kf 4°P}2d;WAQSUD¯VU8kCEQtUD>WCWdF;4:&;WAQtUD>&W>l¯\Y>&FV«^NF2;+B8CEQt;4dkC+FVCBQN@WWT;B\<VeTWd F2>lgr;`° uvCWk4;EQ§§-¬l¢`¦®Nz¤^+z¦h° ¥° H£>&WTd;BDB8UYH£Grf#U8CW`WUDWlUrGrf#UDCkkRU\H°nO*C+FVCB#QN@WWT;B <VeTWd F2>lgr;UDWkU8d;Wk;UDWC{;W;F2CAB > @BDCEQtUD>Wh°j ;E@F>&BD>{e\§§ h¬D¢¥(®±h¥`^S ° h° jiCEQSUD>WCB =x; <2;C+FkR O*>T@WTkUBN°RT; jiCEQtUD>&WTCBm\kCd;g\e >¯ kU;WTk;A<z°HZ@<2kE@(BD> <t«;B8;EQtCB JrU8<2>F2d;+F<qC+WTdMQSRT; >&Ft«BDCk;®&uv> yCk«C+WTdM~(;+FP|o`QNF2;grUQSe0gY@<kE@(BD> <V«;B8;EQtCBd&UN<>&F2d;F<z° jiCEQSUD>WCBhmnkC4d;gre\cF2;A<<2G CA<2RUDW{ Qt>&WnJrO*G§§-° §h° ji>&Fdl<pQSFt>g JnuvG_Jr; Qt;¯SCW>G \U8;+Ft«C+WAQ\=xmnG_uvC+e(d; cH°P}VWTkUd;WTk;>&¯Yd&U8C+{W>h<2;dkC+FVCB QN@W`W;B <VeTWd F2>g ;UDWrC{;+W;+FCB> @(BDCEQtUD>&W(°|vUDd;g U >&B>&{el¥¬ ® ^V h¢° ° c@WW;zQNQ¸uvG ;+{lgYCWJ#XM° >&FV«^SF2;+BDCEQt;4d g#@<2kE@(BN>h<V«;BD;zQtCB0dUN<2>F2d;+F<E®YQSR;;lUDd;giUD>lBD>{lU8k ;E:U8d;Wk;C+WTd#QSR;d;+yCEQt;`° w|PB;AkzQSFV>g\e>{F ~UbW; <2UD>BN° §§ h¬Sz®p^h° z° =x;g\(;BJYGT|6:CW>¯¯¹Gm#giCdUD>Yc"O*G;EQ"CB ° O*>Wh<2;Wl<V@<6kFaUQt;+F2UDC¯S>F-QSR;kB8C <<2U8¯VU8kCEQtUD>&WY>l¯kC+FVCB QN@W`W;B <VeTWd F2>g ;UDWr;+U8d;giUD>lBD>{UDkCB<QN@(d U;T< °Amng c@yBU8k_Xr;4CBQVRl¥¬D¥¥(®Nz¦^+zh¢° . HAL author manuscript. ). ). inserm-00256944, version 1. . . . .
(47) . HAL author manuscript. =x>?A@(;+B8CE@F2; 9\G XrC O*G c";+BDU8;+F2^tO_C4dTe H£O° =n A<;CE@ ;+o +F2UDgi;WQtCB d; <@F:&;UBB8CWk; +UDd g U>lBD>{lU8?A@(;¿d; < QSFt> @yBD; < gY@<kz@hBD>^a<?A@(;B8;EQNQSU?A@(;A< dCWl< B8; < c"C+eh< d;¿B8C uv>UF2;`° @F:&;UDB8BCWk;n;W > @hBCEQVU>&Wr{ W +F2CB8;#dA@Ã<VeTWd F2>g ;~dA@0kCWCBkC+FtlUD;WMdCWh<vB8;H]CUDW;\;EQuv>lUF2; ;+WZ§§ °-}VW<QtUQN@Qnd; :;UB8B8;¸<2CWUQtCUF;G§§ °
(48) "!$#&% ' )($ +*,,-. /0 +12354. 6" 7' 98. inserm-00256944, version 1. z° =x>h<<2U{W>lB H£G Qp>lk+«0G cwCQNFSe\uvG&mF2g1<QSF>&W`{Y¹~°`O*C+FVCB QN@WW;B<VeWd F2>lgY;®rRTCEQwU<ICEQNQSFVUy @QtCEyB8; Qp>~~>FV« qIRT;_H]>WAQSF2;CBTQN@(dAe(° k4kE@\|PW :UF>&W#H;d¦l¬D¢®¢^a¢h° ¢° Qt;E:&;+Wh< O_G @WG¹x;C+F2dOH£G_;QnCBN°6O_CFVCBQN@WW;B<VeWd F2>gr;UbWÃ=x>lk+RT; <Qt;+F2GH UbWWT; <2> QtC+G ¤-Qp>¸l¥`§°+ji;E@Ft>&BD>{el¥¥¬ l¥(®p ^zh¥° ;:. ).
(49) '_µh%8 Jr;A<k+F2U QtUD>&WY>&¯hQSR;UDWkU8d;WAQ"kCA<;A<6>¯-O**®|PB8;kzQSFV>d UDC+{W>h<QtUDk¯UDWdUbW{h<
(50) . !" $#%&(' ) *,+-.. HAL author manuscript inserm-00256944, version 1. &/ 013245 6 7 98: ) <;3%2:=>?7 #A@ CB D2:,+
(51) . E 7FG 84 6>H
(52) 6?#6 1 08I ) 0;J2:47 #JK (2ML,+ . NO?LPH*Q> 6 13 7 98:G )) 7 R7 >,@ PB D2S,+ Q. NO EGT?U VKÃ 4W3XY+ . UZ 6 241 05A ) [;% H 02:79 ]\3 7 4 ) <;% Z >H^
(53) 0 _\6 1 Z 7#`2?H^" >a+ Q. +
(54) ._9Q4+ . +
(55) ._9Q4+ . + ._9Q4+ . . '. h. `b c%d"edfd"g6d7hjidRk6ilnmpoqsr"tvu1w>xay<zk"{l7|"epy]|
(56) oqql y<}6o~61hj~>,eo%>GAd
(57) ~1GA|
(58) dyl y]o7m! _d
(59) mmpl |Fe$h~6,e6lqh9eQd~GJil"me,qphy[eyt ql y[}Gl
(60) |"ehg6l
(61) ij7c%d
(62) ed`d
(63) qll
(64) 9}1ql yy0l
(65) d5yCeGl}Gl
(66) q|
(67) l~ed
(68) 1l`o7mPh=~6|
(69) h>lR~9e|
(70) dyl yF61l
(71) lne=6l_el
(72) e6mpoq]1l"ed
(73) hiy]o ~JeGl!c,|"qh*el"qhjd. '*µh%8?!&}tWkUDd;WTk;>¯-O** C4kk>F2d UDW {\QS>iC+{;G {;+WTd;+F6C+Wdr;g\BD>&egi;WAQ6<QtCQN@<7 U +<8 R". £ £ £ £ ¤f > '. ]?G M>] !nM>] +.¢¡0Q >7 1 +.¢¡0 17 > + 1. PB + 6. PB + 6. 1B h + . 1B + h
(74) . 1B + 6. PB + . PB + 6. 1B + 1. 1B + Q. PB '. . . ' '. . NG M>] !nM>] +.¢¡0Q >7 1 +.¢¡0 17 > + . PB + 6. PB + 6. PB + 6. PB + . PB + . PB + . PB + 6. PB + 6. PB h + 6. PB . . '. . ¥ ) 72I6V9 ¦2I>5§;9#*¨ Q24\^" © ;3©ª>H^ 61 "1 1*H^«4&/7 ¬ \ 79 6 H2 Z f[+ .9?2: >4 73 1% J ) ¤ E \7 *
(75) ® J\3 ""6£<871 "B.
(76) '*µh%!~+%8 2¶(NP 0 V2µ)h2µh%z +
(77) +28 v w!n'x,M
(78)
(79) \2r
(80)
(81) )$ 2`.
(82) 2 .M 0 T$ z4´$ HAL author manuscript inserm-00256944, version 1. 3 _
(83) P
(84) 6!, !?G >B 02: " ]B ) ' &/62:7®F1( &?62:7I9?2419 " CB! )
(85) "61 ]B¤f7 7; >=9
(86) ®6
(87) "6 ,\ )
(88) "6>$ CB*+ &M7 _ >, &D; £ => &/6 -7 R CB*.,*H1£< >=> &/6/ -3 " CB T >£ &?G0 -?\7 R"Q2 1 N G >B 02: " ]B ) 2:7® E >"2:7®247 R CB! )
(89) "61 ]B¤f7 7; >=9
(90) ®6
(91) "6 ,\ )
(92) "6>$ CB4+ &M Q 1 &/; 1£< 11 &/6' -7 R CB*.,*H1£< >=> &/6/ -3 " CB T >£ &?G0 -?\7 R"Q2 1. !a+- .. T +- .. ¡. U! ©+-." ¡ #. 1B !B !B !B PB !B !B. M+ !B . 4+1B . 4+ !B 1. 4+ PB 6. 4+ !B 6. :+ PB 1. 4+ PB 6.. 1B $ 3B G£ !B % PB ) 3B £1B PB ) 3B £1B PB ) 3B £ PB * !B ) PB £ PB % PB ) PB £ PB %. £. !B PB PB PB PB PB PB. :+ !B . :+ !B . 4+ PB 6. 4+ B . M+ PB 6. 4+ PB 6. 4+ PB 6.. 1B ) 3B G£ !B % PB 3 3B £1B % PB ) 3B £1B % PB ) 3B £ PB * 1B ) 3B G£ !B" !B $ 3B £ PB %. . . . . . '. . . '. . . . . £. . . £ £ PB ) 3B%£ PB % PB ) PB 4£ B % £ . . £. . . . . £ £ £ £ PB $ hB 4£ PB £. _7 R"Q5&M6 -* >H $ 0;§8 > 4 ) 0; 7« ]¢+-V."6\^7 >71 >¢ ) ;3¢ 7H\ 6 ;P ¢ 77 >P\P>\H 6V ) 0;/N©>1£0R £+` D1 7« T +-.266H32 Z 7 ,S\^7 >79 04 ), ¤ E j >71 ` G57« ¡ %76 - Q ) 7 >%1 #1<« J ) "7 1J >H\.
(93) '*µh%P\=x;BCEQVU:&;FaU8<V«<6C+WdrCEQNQSFtUy @QtCEyB8;F2UN<V«i¯NF2CkEQtU8>&W<6>&¯O** Ck4k> F2d UDW {\Qt>\UDWdA@<QSFerUDW ;EoT>7<;d\;+F<2>Wl< HAL author manuscript inserm-00256944, version 1. ¡ n
(94) %! + T?UM V . ]M6 1B U = 7HP <H !B 1 0 H
(95) 6 PB>N6H ) 1
(96) [H *6 !B E 0# 1%$>H^ 5 PB T >£ &M6 -$M\3 ""6 1 NG 1B U = 7HP <H !B 1 0 H
(97) 6 PB>N6H ) 1
(98) [H *6 !B E 0# 1%$>H^ 5 PB T >£ &M6' -?\^7 RF6"1. !a+- .. T +-.. ¡ . U! ©+- ." ¡ #. !B PB A1B PB !B. h%+ B 6.. !B ) ^B £ CB % !B )V5B £ PB % !B!VB £ !B % 1B )VB £ !B". PB $ 3B £ h1B £ !B! 3B £ !B % PB ) 3B £ PB" £. 1B $ 3B £ !B % PB ) PB £ !B % !B )VB £ !B % PB ) 3B £ PB *. £ PB ) PB £ B CB $ ^B 4£ PB £ £. :+ PB 6. %+ PB 6. :+ !B 6. 4+ PB 6. . . . . '. . . . . h%+ PB 6. M+ B
(99) .. B B !B 1B PB. . :+ !B 6. M+ PB 6. 4+PB 6. '. . . . . . . . . . . . % _7 R"6 &(6 '-:>H j( <;3%83 > ) [;%9
(100) 7«]a+-."69\P 171 3a ) <;*>H^ 0 84( [;J77 1 \>\H7 64 ) <;JN©1*1£0R £+f %1 « T +-."69GH32 Z 7 D\^7 >71 J ) ¤ E j 79 _ 6
(101) 7« ¡6 - Q ) 7 11 0#1<« % ) 7 "7Q >JQ >H\V« ª \P ) 4
Documents relatifs
To test whether the vesicular pool of Atat1 promotes the acetyl- ation of -tubulin in MTs, we isolated subcellular fractions from newborn mouse cortices and then assessed
Néanmoins, la dualité des acides (Lewis et Bronsted) est un système dispendieux, dont le recyclage est une opération complexe et par conséquent difficilement applicable à
Cette mutation familiale du gène MME est une substitution d’une base guanine par une base adenine sur le chromosome 3q25.2, ce qui induit un remplacement d’un acide aminé cystéine
En ouvrant cette page avec Netscape composer, vous verrez que le cadre prévu pour accueillir le panoramique a une taille déterminée, choisie par les concepteurs des hyperpaysages
Chaque séance durera deux heures, mais dans la seconde, seule la première heure sera consacrée à l'expérimentation décrite ici ; durant la seconde, les élèves travailleront sur
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
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
Attention to a relation ontology [...] refocuses security discourses to better reflect and appreciate three forms of interconnection that are not sufficiently attended to