• Aucun résultat trouvé

Les cancers professionnels (à l'exception de l'amiante)

N/A
N/A
Protected

Academic year: 2021

Partager "Les cancers professionnels (à l'exception de l'amiante)"

Copied!
13
0
0

Texte intégral

(1)Les cancers professionnels (à l’exception de l’amiante) Danièle Luce, Marcel Goldberg. To cite this version: Danièle Luce, Marcel Goldberg. Les cancers professionnels (à l’exception de l’amiante). ONCOLOGIE / La Revue Francophone de Formation en Oncologie, 2007, 9, pp.1-4. �10.1007/s10269-007-0596-2�. �inserm-00150018�. HAL Id: inserm-00150018 https://www.hal.inserm.fr/inserm-00150018 Submitted on 11 May 2010. 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 ONCOLOGIE / La Revue Francophone de Formation en Oncologie 2007; 9 1-4.  

(3) 

(4)    !"$# $% '&(  

(5) & )  *+,-" %./ 0 ) % 12 

(6) 34#%5 768%2(79"

(7) % &32 $

(8) 7/ HAL author manuscript. :<;7=>@?BA@CEDF.GC-HI JLKNMO;7PQGCARTS AVUXW$C7PYZHI J [1\^]=_LC7PL`ba1=>dcfehg ijK [k'P4F.ChU^F<l-;7AUmon<_L=XCK pqkk[srut;7>+=^cMv;8FPL>+GC wx\^]4yz{gpKqlZ>|A@A@CQ}F.>~ >dc€PLChGSqFPc(\^‚;7=XGC7PN_ƒPQS$~€Cq_N_L>VS ==CA"_. inserm-00150018, version 1. MOS^cL_Q„GA+e'\qG;s=GC7PƒPQS$~€C^__L>VS ==CA+KC7 ƒS_L>dc>VS$=-ƒPQS$~€Cq_N_L>VS ==CAA@CK>|=XUC`†=>"_‡;8c€>+S=KƒPLe8ˆ$CB=‰c>VS$= Š1C7‹-Œ<S$PLU _8\^SGG8Fƒ;c€>+S$=X;AG;=XGC7PLKS GG8Fƒ;Žc€>VS$=X;BA.C7 ƒ.S2_€FPLCKGsS$`1ƒC= _Q;8cf>+S$=XK$ƒPQC8ˆC=^cf>+S=.

(9) w. HAL author manuscript.  . A F_-UC A; `'S >dcf>@e UC^_1G‰;=GesPLS$Y?s=C^_1;7ˆ.e7PLe^_1G C

(10) Am XS `'`*C _QC3c€PLSqFˆCs=^cZU;s= _-A€m"C=qˆ> PQS$==XCB`*C=^c ƒPLS~€C^_N_L>VS ==CA@KC8c A€mC7 ƒS_L>dcf>+S=UCq_ G;=G‰e7PLSY?7=C‰_hƒPLS~€C^_N_L>+S==CA"_ZGS=G‰C7P=XC7PL;>dc C= yPL;7=GC†ƒAVF!_ UChUC8F *`>@AA@>+S = _ UCEƒC7P_LS==C^_BD Cq_C7 ƒS_L>dcf>+S= _ƒP‡S~€C^__L>+S ==XCBA@A@C^__LS=^c;^_N_QS G>+eC^_hUC5=XS `-WPLC8F . inserm-00150018, version 1. c"‹ƒCq_*UC G;7=GC7PD C ƒSXF`'S=OC^_€c-A€m@S$PY;s=C G>VW.A@C A@C ƒ A F_~"PLe^F.CB=‰c'UC‰_*G;=Ge7PQS$Y?7=XC^_*GC7P€cf;B>+=_QK _4F.> ˆ>!UCTA@;1ˆ$C^__L>@CKUCTA@;TƒC;8F.KUCq_A@C8F2Ge`'>Cq_QKUCq_G‰;7=XG‰C7PN_=X;q_LS„ _L>+=^F_L>@C=_LKU^F ~€S >@CZC8cU^F A@;7P‹X=q .K `*;>_ ƒPL;8cf>^F.C`*C=^cc€SqF_EA@C^_c4‹ƒC^_ UCG;B=XG‰C7PEƒC8Fˆ$C=^c8coPLCGsS=GC7Pf=e^_ AdF_L>@C8FPN_h`*>AA@>@C7PN_ UCG;q_ UC G;=GCsP _LS=^c<U^F_*G ;^F.C ;==eC UCq_*C7 ƒS_L>dcf>"S= _'ƒPLS~€Cq_N_L>+S==CAA@Cq_LKE`*;>"_ _QC8FA@C`*C=^cx[. r . We=XeB~€>@G^>@C=^c Um F=XC PLCGS$==;>"_N_‡;=GC C= `*;A@;U$>@C ƒPLS~€Cq_N_L>+S ==XCAA@C! D C‰_ C XƒS2_L> c>+S=_. ƒPLS~€C^_N_L>VS ==CAA@Cq_ GS=^c€P> WF.CB=‰c~€SPcfC7`<CB=‰c;F >+=e7Y;A>+cfe^_h_LSG7>+;A@C^_ UC'`'S$P€cf;BA+>dcfe'C8c Um>+=G>@UC=GC'UCq_ G;7=GC7PN_Z‚C7ƒC=U;=‰cfK<AVC PL>_"^F.C UC G;=XGC7P ;^__QS G>+e# GC^_ C8 XƒS2_L> c>+S=_ ƒCFc$Žc€PLC PLC7A@;8c€> ˆ.C`*C=^c ~f;G>A@C`C=‰cƒPLe8ˆ$C=^F.K ƒ;7PF=CZeA+>`>+=;8cf>+S=*UC^__4FW_4cf;7=XGCq_A@C^_ƒ A F_ =SGB> ˆ$C^_ C8cƒ;7PF=CZU>|`*>+=qFc>+S= UC^_=> ˆ.C;F *U&% C7 ƒS_L>dc>VS$='. (*) ,+,- .0/1+ MOSPLC c2 X;=3 X;BA@~'S ~hc2 C PLCGS$Y=>

(11) ‰CU G;7PLG>+=SYC= _3;7P‡C ~"PLS ` SGG8Fƒ;8c€>VS$=X;BA S$PL> Y>+= ;7=XU{>+= y2PL;=GC ;8W$SXFc w `'>A@A>+S = S ~Œ'SP54C7P‡_-;sPLC C ƒS_LCU687ZA`'S_4c5C8ˆC7P‹ _L>dcfC S~ZG;=GC7P-`*;7‹ W.C >+=qˆSAVˆ.CUK c2 C A F=Y W$C>|=Yc2 XC-`'S2_€c~"PLC^F.C=^c S$PfY;7=u~€S$A+A+SqŒ*CU†W‹*c2 C5WA@;UUC7PLK c2 XC†_54>+=K AVC8F&4C`'>@;K c2 C-=S_LCK$c2 C A> ˆ.C7P ;=Uc2 CA@;7P‹X=q 9# >@ACu_LC7ˆCsPL;A c2 SqF_L;=XU _ S ~G‰;^_LC‰_hSGG8FP C;G ‹C;sPE>+= yPL;=XGCKS=A|‹O['cfS. r! ;7PQC-GS `-ƒC=_L;8cfCU6nZGG8Fƒ;8cf>+S=;A!C7 ƒS_4FPLC-GS$=qc€P> WqFcfC^_A@;7PYCA+‹cfSc2 C†_QS G>+;A>+=C^F2;A+>dc>@Cq_>= G;7=GC7Pu>+=GB>@UC=GC ;B=XU `'S$P€cf;BA+>dc€‹';:<SqŒ'C8ˆ$C7PLKhSGG8Fƒ;8c€>VS$=X;BA1G;=GC7PuGSqF.A+U{W$C A;sPYCA|‹ ƒPLC7ˆC=^cfCU c2 qPQSXFY0 -c2 C1CBA+>@`>+=;8cf>+S$=3S ~c2 C-`'S_4c!c€Sq >+G-SGG8Fƒ;8cf>@S$=X;AC7 ƒS_4FPLC^_ ;=U†c2 C1GS$=‰c€PSAS ~C7 XƒS2_€FPLC A@C7ˆCA"_.

(12) . HAL author manuscript. = UC1 XS$PN_ UC A4m@;`>@;=^cfC"K'UC =XS$`-WXPLC8F G;=Ge7PLSY?7=Cq_ _QS$=‰c ƒPLe^_QC7=^cL_ U;7=_ A€mC=qˆ>+PLS==C`*CB=qc ƒPLS~€C^_N_L>VS ==CA2qD CX_ e8c"F.UC^_ C7=u`'>A>@C8FxUChc€PL;8ˆ;>@AS$=‰c}LSqF.e5F=*PA+C-`;}‡C8FPU;s=_A4m@>UC=‰c>+~>@G;8cf>+S=uUC _4FW_€cf;7=GCX_ G‰;=GesPLS$Y?s=C^_ >@CB= ^F.C-A@;5ƒA Fƒ;7P4c UC^_=‰F>"_‡;=GC‰_ƒPLe^_QC=^cfC^_ C=u`>+A>@C7FuƒPQS$~€Cq_N_L>VS ==C‰A _LC-PLCc€PSqFˆC=^c e7Y;A+C`*C=^c U;B=_hA€m"C=^ˆ>+PLS==C`*C=^cfKA+Cq_c€PL;8ˆ$;>A+A@CFP‡_T_QS$=‰cE_QSXF`'>"_ *UC^_ C XƒS2_L> c>+S=_. inserm-00150018, version 1. ƒAdF_E>+=‰cfCB=_QC^_ C8c ƒ A F_ A+S=qYqF2C^_D CX_PL>"_,^F.C‰_ UC†G‰;=G‰C7P A+>eC^_GC‰_T_€F W._4cf;7=XG^C‰_h_LS=^c US$=XG3_QSXFˆ$C=^c GS= _€cf;8cfeC^_xC7= ƒPLC`>@C7PxA|>@C7F C= `>A@>@C8F UC c€PL;8ˆ$;B>@A+K'C8cF=XCvƒPQS$ƒXS$P"c€>+S=b>`'ƒSPcf;s=^cfCOUC^_x;7YC=^cL_ ;G8c"F.CsA|A@C`*C=^c GS= _L>@Ue7PLe^_ GS `'`*C†G;B=XG‰e7PLSY?7=C^_ ƒSXFPA€m XS$`'`*C'S$=‰c e8cfe-`†>"_ C=ue7ˆ>@UC=GCTƒ;7P U Cq_ e8c"F.UC^_ UCEYPSqFƒC^_ƒPS~€Cq_N_L>+S ==XCA_ D C ‚C=^c€PLC >+=^cfC7P=X;8cf>+S$=X;A UC PLCG XC7PLG C _€FP A@C G;7=GCsP‚]4z ‚ ƒqFWA@>@C PLe7YqF.A>@?7PLC`*C=^c UC^_ `'S =XS$YPQ;7ƒ0 >@C^_ _4FP A+; G;=G‰e7PLSYe7=>@G>dcfe Um@;7YC=^cL_ G1 >`*> ^F.C^_LK ƒ q‹._L> ^F.CX_QK W>VS A+SY > ^F.C^_QK UC GS`-ƒS_Le^_ZCch`'eA@;=qYCq_ZGS `1ƒ A@C7 Cq_LKUCƒPLSGeUe^_Z>+=U^F_4c€Pf>+CA_5SXF UCuG> PLGS=_4cf;s=GCq_ZUm@C7 ƒS_L>dc>VS$='. SXFXP G1 X;^F.C ;7YC=^cfK A+; `'S =XS$YPL;sƒ0 >C GS `-ƒPLC=XU A€me7ˆ;A F.;8cf>+S= UC _‡; G;B=XGe7PLSYe7=>@G>dcfe ƒSqFP A€m S`†`*C! D C{cf;WAC;8F [ ƒPLe‰_LC7=‰cfCbA+Cq_ ;7YC=‰cL_ SqF `<eBA@;=YC^_OUC A€mC=qˆ>+PLS==C`*CB=‰c ƒPfS$~€C^__L>VS ==CA GA@;^__Leq_ GS`'`C U C‰_uG‰;=GesPLS$Y?s=C^_ €YPLSXFƒC [

(13) \ >+A"_*PLC7ƒPLe^_‡Cs=^cfC7=‰c'ƒ A F_3UC A@;v`'S>dc>Ve UC^_ ;7YC=^cL_3UC G‰C YPLSqFƒC N[, D ; Ue~€>+=>dc>VS = U m F= G;=XGe7PLSY?7=CuƒPLS~Cq_‡_L>+S ==CAC‰_4cZGC7ƒC=U;=^c5Uq>_QG8Fcf;8WA@C!*C _LS=^c ƒ;^_'>+=GA F_>@G>EA@Cq_'`*eU$>@G;`*C=^cL_<SXFOˆ> P4F!_LK;8F &^F.CA4_1ƒC8FˆC=^c8c€PQC GC7ƒC7=XU;=^c1C7 ƒS_Le^_*GC7P4cf;7>+=_ c€PL;8ˆ$;>|A@A@C8FPN_ 7 A4m">+=qˆ.C7PN_QCK _QS$=‰ch>+=GA F_1A@C3cf;8W$;7Y>_L`*C ƒ;‰_N_L>+~ZC8cZA+CuPL;7‹XS ==C`*C=^c-_QS$AV;B>+PLCK ^F>_LS=^c Ye7=Xe7PL;A@CB`*C=^c GS= _L>@Ue7PQe^_OGS `'`*C UC^_OC7 XƒS2_L>dcf>+S=_OC7=qˆ>+PLS==C`*C=^cf;A+Cq_LK `<;B>"_O;F ^FCA"_ _LS=^c C8 XƒS2_Qe^_†F.=OYPL;7=U =XS `-WPLC UC c€PL;8ˆ$;>|A@A@C8FPN_  UC^_u=> ˆ.C;F {eAC7ˆ$eX_n5=OƒC8Fc*GS$=_4cf;NcfC7P ^F.C A+Cq_. !"#$&%'%)(+*-,/.

(14) 102,43(!0*568798;:8(10"31(=<.

(15) k. HAL author manuscript. G;7=Ge7PLSY?7=C^_1ƒPLS~C^__L>VS$==CA"_'=C _LS=^cZƒ;‰_'A|>@`>dcfe‰_  F=C G‰;8cfesYSqP>+C ƒ.;7P4c€>+GFA@>?sPLC UC _4FW_€cf;7=G‰C^_QK `*;>_<GS `-ƒPQC7==C=^c  A+; ~€S >"_1UC^_';sYCB=‰cL_Zƒ0 q‹_L> ^FC‰_‡KGS`†`*C A@C^_ZPL;7‹XS ==XCB`*C=^cL_1>+S =>"_L;=‰cL_-SqF A@C PL;7‹XS$==XC`C=‰ch_LS AV;B> PNCKUC^_hƒSqF_N_L>@?7PLC^_ >|=0 ;A@;7WA@CX_ N _L>+A>@GCKƒSqF_N_L>@?7PLC‰_ZUC†WS >"_ LKUC^_ GS `-ƒS_Le^_5U C `*e8cf;8F  ;7P‡_LC=>@GK G;U`> F.`'K =>@G 4CA+KxG PLS `'C LK UC^_ `eA@;=qYC^_ Um q‹UqPQS G;sP4WqFPLC‰_ ;sPLS `';8cf>^F.Cq_. inserm-00150018, version 1. ƒSAV‹$G7‹GA> ^F.Cq_  ^ F.>A@Cq_ `*>|=esPL;AC‰_LK YSqF.UqPS= _QK _4F.>@Cq_; LK CcOUq>+~4~fe7PLC=‰cL_ ;Fc€PLC^_ ;7YC7=‰cL_ G >`> ^F.Cq_. 1 AVS$P4FPQC†UCTˆ>+=‹ACK~€S$PL`';A@Ue q‹UCK!SX ‹XUC†Um@e8c2 q‹A@?=C  = UC XS$P‡_ UC†GC^_ ;7YC=^cL_ SqF `<eBA@;=qYCq_QK. G. ƒAdF_L>@C8FP_uƒPLS~€C^__L>+S =_ SXF >+=U^F_4c€PL>+Cq_ _QS$=‰c3e7Y;A+C`C=‰cuGS$=_L>+U esPLeC^_ GS `'`C G‰;=Ge7PLSY?7=C^_3ƒSXFP A€m S`†`*C  ;7WAC;8F w  ]A_m";7Y>dc UmVF.=C'e7ˆ;A F.;8cf>+S=uY A+SW;A@CK ^F.>=XCGS=GCsP =XC-ƒ;^_E=XeG‰C^__L;> PQCB`*C=^c c€SqFqcfC‰_ AVC^_ C XƒS2_L> c>+S= _OƒPLe‰_LC=^cfC^_vU;B=_ A€m>+=U^F!_4c€P>@CK C8c ƒC8Fqc ƒ;7Pf~€S >_OPLC~4A@e8cfCsPOUC^_OGS=U>dcf>+S =_ Um@C XƒS2_L> c>+S= ;=G>@CB==XC^_6 SXFPZGC7Pcf;>+=C‰_ZU CuGCX_ ƒPLSq~C‰__L>+S = _5SXF >|=XU^F_€c€P>+Cq_LKA4m@;7YC=^c G;F_L;A;ue8cfe `>"_ C=*eˆ>@UC=GC F.Adcfe7PL>+C8FPQCB`*C=^cfK.GS$`'`*CTA+Cq_ƒSqF_N_L>@?7PLC^_ UCEWS >@_(ƒSqFPA+;T~€;7WPL>@G;8cf>+S=UCZ`'C8FWACq_QK ƒSqFP-Um@;8Fc"PQC^_LKGS$`'`*C A@C^_-ƒC>+=^c€PQC^_1SXFOA+Cq_hc€PL;8ˆ$;>AAoC8FPN_1U^FOG;SXFcfG SqF.G A€m@;7YC=^chPQC^_ƒS= _Q;WA@C U^F PL>_,^F.CheA@C7ˆehUChG;=XGC7P=m@; cfS^Fs}LSXFP‡_ƒ;^_e8cfeE>VUCB=‰c>+~€>"e! ‚C7P4cf;7>+=_OUC G‰C^_vG^;=XGe7PLSY?7=C‰_ =C _QS$=‰c ƒ AdF!_ Fcf>+A>"_Leq_LK SqF GS$=XGC7P=XCB=‰c F= ƒCc€>dc =XS$`-WPQC U C c€PL;8ˆ$;>|A@A@C8FPN_ C= yPL;s=GC f GS$`'`*C A@C Y;

(16) `'SXFcf;sPUC ƒ;7P C8 C`'ƒ A@C   :um@;8Fc€PLC‰_ _QS$=‰c C7=XGSPLC GSqFPL;7`'`*C=^cxC`-ƒA+S$‹eq_ D Cvcf;8WA@C;F  >+=U$> ^F.C ƒSqFP A+Cq_ C XƒS2_L> c>+S=_ A@Cq_ ƒAVF!_ ~"P‡e^F.C=^cfC^_ A@C =S`<WXPLC-UC5c€PQ;8ˆ;>A@A@C8FPN_C7 XƒS2_Qe^_Cq_4cf>+`*e Tƒ;7P4c€> PUC-A4moCB= ^F'8cfCtqF.`'C7Pwrr0 w/fK ^F>=XCTƒS$P€cfC ^F.C _4FP A@C^_T_Q;A;sP >@e^_QKC8c;-ƒ;sP4c€> P UCA@;<W;q_QC†UC'US$==XeCq_h‚;7PQC8 ƒC=XU;B=‰cA@;-ƒe7PL>+S UC [sppr„7[spp06.‚C8c"cfC W;q_QC UC US$==e‰C^_ PL;‰_N_‡C`-WAC UCq_ >+=~€S$PL`*;8cf>+S= _ _4FP A+C^_ C7 XƒS2_L>dcf>+S=_ ƒPLS~€C^__L>+S==CA|A@Cq_ ;8F G;7=Ge7PLSY?7=C^_ C= (FPQS$ƒCZCŽcƒC8Pf`CcUCh~€SXFP=> PUC^_ Cq_4c€>+`*;8cf>+S=_(ƒ;sP(ƒ;7‹_  ^D C^_ C7 ƒS_L>dcf>+S= _A@Cq_ ƒAdF_ ~"P‡e^F.C=^cfC^_ Um@;7ƒPL?^_ ‚;7PLC7 =S= eˆ$;AVF.eCX_ U;7=_ tqF`'CsP _LS=^c{AC PL;7‹XS$==XCB`*C=^c _LSA;> P‡C 7[. rr'rrr c€PL;8ˆ;>+AA@C8FP‡_'C7 ƒS_Le^_ 'C8cZA+Cucf;8W;7Y>"_N`*C ƒ;^_‡_L>~ 7 [wrr'rrr c"PL;ˆ;>+AA@C8FP_'C8 XƒS2_Qeq_;  =. UC1 XS$PN_*UC GC‰_uC7 ƒS_L>dcf>+S= _LKEA@C^_3G;=Ge7PLSY?7=Cq_*AC‰_ƒAdF_*~4PLe^F.CB=‰cL_u_LS=^c'AVC^_†WXPLSqF>+AA@;7PQU _*U m@;G>@U C.

(17) . HAL author manuscript. _4F.A+~FPL> ^F.CKhA+C ~€SP `<;BA@Ue q‹UCK5A@C^_*ƒSXF_‡_L>@?7PLC^_3UC W.S$>@_LKhA; _L>A+>@G‰C G7PL>"_4cf;A+A+>|=C Cc'A+C WC=

(18) ‰?=C!(D C^_ C^_€c€>|`*;8cf>+S=_ UC†tqF.`CsPC8c ‚;7PLC8 *=C-_LS=^cƒ;‰_U> PLCG8cfC7`*C=^cGS$`-ƒ;sPL;7WACq_QKG;7P CA|A@C^_ _LS=^c SXW‰cfC7=‰F.C^_  ƒ;7P4c€> PUC-`ec2 SUS$A+SY>+C^_ U>|~f~e7PQCB=‰cfC^_#A+A@C^_ US$==C=^c GC7ƒC=U;=^cF=3S$PLUqPQC-UCTYPL;=UCFPE_L>`*>A@;> P‡C'\ ;8F c€S^cf;7AVKA4m@C7 ƒS_L>dcf>+S$=$'UC^_ G;=Ge7PQS$Y?7=XC^_ƒPLS ~€C‰__L>"S=q=CA"_ 5 SPN_cf;8W$;7Y >"_L`*C-ƒ;^__L>+~KPL;7‹XS ==C`*C=^c. inserm-00150018, version 1. _LSA@;> PLChC8c;`'>;=‰cfC  GS=GC7Pf=C7PL;>dcC=TyPQ;B=XGCEƒAVF!_UChUC8F *`*>AA+>+S=_UCEƒC7PN_QS$==XCX_^]fA _Žm;7Y>dcUCEƒAVF!_ Um@C^_4cf>+`;c>+S= _ U C A€m@C XƒS2_L> c>+S= vF.= `'S `*C=^cxUS$==eK'C8cxA+C =S `-WXPLC UC ƒC7P‡_LS==Cq_ ;7‹;=‰cxe8cfe C8 XƒS2_QeC^_;8F3GSqFPN_UCEAVC8FPˆ>@CEƒPLS$~€Cq_‡_L>+S ==CA@AChCq_€cƒPLSqW;8WA@C`*CB=‰cc€PfS$>_ SXF ^F.;Nc€PLCE~€S$>"_ƒAdF!_eA+C7ˆ.e! ‚C^_xC^_4cf>+`*;8c>VS$=_ _LS=^c C7= SXFc€PLC W;^_QeCq_ _€FP A+Cq_xG;=GesPLS$Y?s=Cq_x;ˆ$e7PLe^_hnhP ƒAdF!_L>CFPN_xeBA@e`*C=^cL_ `'S =‰c€PLC7=‰c ^F.CuUCu=S`<WXPLC8F G;=Ge7PQS$Y?7=XCq_hƒPLeq_LC=^cL_5CB= `'>A>@C8FvUC3c€PQ;8ˆ;>+A=m@S$=‰cEƒ;‰_-C=XGS$PQCue8cfe >@UC=^cf>|~€>@eq_ :<C^_EPL>"_,^F.C‰_heA@C7ˆeq_hUC*G;=GCsPhS=^c eNcfe'S^W_‡C7P4ˆ$eq_hU;= _ UC=S`<WXPLC8F_QCX_ ƒPLS~€C^__L>+S=_hSqF >+=U^F_4c€PL>+C^_ _Q;=_^F.C A@; SqF AC‰_ _4FW_4cf;s=G‰C^_ PQCX_fƒS$=_Q;7WAC‰_ ;B>@C=^cxecfe ƒSXFXP A€m>+=_4cf;=^cxGA+;>+PLC`*C=^c >@UC=^cf>|~€>@e‰C^_ ;7P;>|A@A@C8FPN_LKqF=C c€PQC7=^cf;>+=ChUChG;=XGe7PLSY?7=Cq_ƒPQSXW$;8WA@CX_ 4 YPLSqFƒCEw07bU^F3‚]4z ‚  CŽc!ƒAdF!_ UC GC7=^c5G;7=GesPLS$Y?s=C^_ZƒS_N_L> WA@C^_ 4 YPQSXFƒCuw# U^FO‚]4z ‚ ' _LS=^cZUC‰_-C ƒS_L>dc>VS$=_TƒPQS$~€Cq_N_L>VS ==CAA@Cq_ ˆ$S > P. ƒ;7P C8 C`-ƒA@C  k/ ƒSXFP F=XC A+>"_4cfC C8 & X;8F_€c€> ˆC  O]LA _Žm";7Y>dc C^_N_QCB=‰c>VCBA@A@CB`*C=^c Um@;7YC=^cL_. G;7=Ge7PLSY?7=C^_1ƒSXFP1A4m@;=>`*;AƒSqFP-A+Cq_,^F.CA"_'A@CX_<USq==eCq_<e7ƒ >VU e`'>+S A+SY>^F.Cq_*_LS=^cZƒSqFP-A"m@>|=_€cf;7=^c A>@`>dcfeC^_ SqF >+=_4F.~4~>"_‡;=^cfC‰_h]A'Cq_4cxUS$=XG =e‰GC‰__L;> P‡C UC ƒSXFXPN_4F.> ˆPLC UC^_ PLCG XC7PLG C‰_ ƒC7PL`*C8c"cf;7=‰c Um>@UC=^cf>+~4>@C7P C8c UCGA@;7PL>~f>CsPhAC‰_hPL>_"^F.C^_ZUC*G^;=XGC7Ph;q__QS G>+eC‰_ UCq_ C XƒS2_L> c>+S= _ ƒPLS ~€C^__L>+S==CAA@C^_QK. ^F.>ƒC8FˆC=^c A+; ~€S >"_'GS$=‰c€P> WqF2C7P  A€m;`*eA>+SPL;8c€>+S=OUC A+; ƒPLe7ˆ$CB=‰c>VS$= CB= `'>@A>@C8F UC c€PL;ˆ;>A C8c >@UC=^cf>|~€>@C7P UC‰_ ~f;G8cfC8FP‡_ CB=qˆ>+PLS==C`*C=^cf;8F ƒSqFˆ;=‰c G;F_LC7P UCq_ G;=GC7PN_ U;=_ A@;{ƒSƒqF.A+;8cf>+S = Ye7=Xe7PL;A@C! D C^_ZC7 XƒS2_L>dcf>+S=_hƒPLS~€C^_N_L>VS ==CA|A@Cq_-_QS$=‰ch;‰_N_LSG>+eCq_ uUC=XS `-WPLC8F xc4‹ƒCq_ZUCuG;7=GC7PD CƒSXF`'S= C^_€cA4m@SPY;7=CZG> WA@C-A@C5ƒA F_ ~"PNe^F.CB=‰c  G~,^cf;WAC;8F [

(19) LK_F> ˆ>UC-A@;5ˆ.C^__L>@CKUCZA;ZƒC;8F.KUCq_[email protected]‰e`'>@C$_ UC^_ G;=G‰C7PN_=X;X_QS „L_L>|=‰F_L>@CB=_QKU^F ~€S >VC†Cc U^F A+;sPQ‹X=q ]A~f;8Fc GC7ƒC=XU;B=‰c=SqcfC7P ^F.CT=XC†_LS=^c >+=U$> ^Feq_.

(20) g. HAL author manuscript. U;7=_<GC cf;8WA+C‰;8F ^F.C A+C‰_'G;=G‰C7P‡_-ƒSqFPTA@C^_"^F.CBA@A@CX_'A@; PQC7A@;8c€>+S= ;7ˆC‰G A€mC7 ƒS_L>dcf>+S= C^_€c1GS$=_L>+Ue7PLe‰C GS`'`C e8cf;WA>@C! D Cq_ G;=XGe7PLSY?7=Cq_ ;7ˆesPLe^_ SqF ƒPLSqW;WAC‰_ _QS$=‰c e7Y;A+C`*C=^c ƒAdF!_ SXF `'S >+=_ ~€SP4cfC7`'C=^c _QSXFƒ S$==e^_ Um";8FY`C=‰cfC7P A+C PL>"_,^F.C Um;8Fc€PQC^_ c"‹qƒ.C^_ UC G;=GCsP ;sP C8 C`-ƒA@C‰K A€m"C7 ƒS_L>dcf>+S$={;8F ~€S$PL`';A@Ue q‹UC Cq_4cu_€F_ƒCGcfeC Umc€PLC ;^__QS G>+eC ;8F {AC7F.Ge`*>C‰_LKhA4moC XƒS2_L> c>+S= ;8F. inserm-00150018, version 1. G;U`'> F` ;8F G;=G‰C7P UC A+; ƒPLS_4cf;NcfCKEA€mC7 XƒS2_L>dcf>+S= ;8F c"P>@G A+SPLe8c2 q‹A@?=C ;F G‰;=GC7P U^F PLC>|=XKTA+Cq_ >+=_‡CG8cf>+G>@UC^_E=XS$=3;7PN_QCB=>@G‰;8F ;8F G‰;=GC7PN_U^F GC7Pˆ$C;7F.K ;F A|‹`'ƒ XS `'Cq_=S= :<SUqY04 >+=>@C=_C8c ;8F `†‹$eA+S `*Cq_u`-FAdcf> ƒA@CX_nT=OƒC8Fc*e7Y;A@C`C=‰c'ƒC7= _‡CsP ^F.C A+C PA+C Um@C7 ƒS_L>dc>VS = _*ƒPLS~C^__L>VS$==CA+A@C$_ U;7=_ A;-_4FP€ˆ.CB=‰F.CTUCZG;=GC7PN_Y$‹X=e‰GS$AVS$Y>^F2C^_LKCs=†Ye=Xe7PL;AGS= _L>@Ue7PLeZGS `'`*CT~f;>VW.A@CKC^_€cƒC8Fc„5Nc€PLC _LSqF_L„fC^_4c€>+`*e C= PL;>"_LS= U^F ~f;B> W.A@C =S `-WPQC Ume8c"F.UC‰_ƒSPcf;s=^cu_€FPuAC‰_u~C`*`Cq_   (:<C^_*P >"_"^FCq_ eA+C7ˆeq_UChG;=XGC7PUChA4m@Sqˆ;> P‡ChS$=‰c!ƒ;7PC8 $C`-ƒ A@Che8cfeh`'>"_C='e7ˆ>UC=XGChG C

(21) TAVCX_ GS$>+~~fC8F_‡C^_QK$ƒAdF_L>@C7FPN_ e8c"F.UC^_O_4FYY?sPLC7=^cxF=C PLCA@;8cf>+S$= C=^c€PLC C8 ƒS_L>dcf>+S= ;8F ƒC7PQG1 A+SPLe8c2 q‹A@?=C C8c G;7=G‰C7P U^F GS A3U C A€m|Fcfe7P4F_QK C8c ƒAdF_L>@C8FPN_ C7 ƒS_L>dcf>+S= _ ƒPLS~€C^__L>+S ==CA+A@Cq_ 4 ƒC^_€c>VGB>@UCq_ SPY;7=XS G A+S$PQe^_LK _LSAVˆ$;=^cL_ SPY;7=>^F.C^_ _LS=^cZ_4F_fƒCG8cfeC‰_ZUm;FY `*C=^cfC7PhAVCP >"_ ^F.CuUCuG;s=GC7PZU^FO_QCB>+='2y!>+=;AC`*C=^cfKA+SPN_,^F.C A€mS= C8 ;`*>|=C A€m"C= _QCB`-W.A@C UCX_ ;^_N_QS G>+;8cf>+S=_ C7=‰c€PLC C8 ƒS_L>dcf>+S= _ ƒPLS~fC^_N_L>+S==CAA@Cq_ C8c G;7=XGC7P _4FYYesPLeC^_ƒ;sP(A+;hA+>dc"cfe7PL;c"FPLC7KƒPL;Nc€>^F.C`*CB=‰cc€SqF_A+Cq_c@‹ƒCq_UChG;s=G‰C7PƒC8Fˆ$CB=‰c 8c"PLChGsS=GC7Pf=eq_ a1=G‰C7P€cf;7>+=<cfC`-ƒ_ UCTA@;8cfC7=GCZCq_4c=eGCq_‡_L;>+PLCT;7ˆ$;B=‰c ^F.CTA€m@C~4~fC8cG;B=XGe7PLSY?7=XC†_smC7 XƒP >+`*C!‚ C cfC`-ƒ_ C^_€cˆ;7PL>@;7WACK `';>"_EA@CTƒA F_h_LSqFˆC=^cfKA+C-G;=XG^CsPE_4FP4ˆ>@C‰=^cZ[sru;7=_QK2wru;=_SqF ƒ AdF!_;sƒPL?^_A@C'UeWFc UC A€m"C7 ƒS_L>dcf>+S$='4= PL;>"_LS= UCGC8c"cfCA+S=qYqF.C†ƒesP >VS UC*CB=‰c€PLCA"m"C7 XƒS2_L>dcf>+S= CcEAV; _4FPˆC=^F.CK A@C^_ZG;B=XGC7P_ Um@S$P> Y >+=C ƒPLS~€Cq_N_L>+S==CAA@C _QS$=‰c'_LSqFˆC7=‰c1U$>+;sY =XS2_€c€>XF.e‰_';7ƒPL?‰_ ^F.C A€m;Gc> ˆ>dcfe ƒPQS$~€C^__L>VS ==CAA@C ;>dc GC^_‡_Le! ‚ CGB>1C7 ƒA> ^F.COCB= ƒ;7P4c€>@C^F.CvA@; ƒPL>_QC C=bG ;7PYC `*e‰U$>@GS„ _LSG7>+;A@C UCOGCq_ G;=G‰C7PN_x_LS >dc _LSqFˆC=‰c>+=_4F.~~>"_L;=^cfC .

(22) j. HAL author manuscript. ‚C7P4cf;7>+=_xG;=GC7PN_ ƒC8FˆC=^c C7= CB~€~fC8c ~€;>|PQC A€mSqWs}‡C8c Um F=XC >+=UC`†=>"_‡;8cf>+S= ;8Fbc€>dc€PQC UC^_x`';A@;U$>@Cq_ ƒPLS~€C^_N_L>VS ==CAA@Cq_& a1=Cec"F.UC†PLeGCB=‰cfC;*GC7ƒC=U;=^c`'S=^c€PLe ^F.C _LCFA@C`*CB=‰c'[ C8c r  UC^_ G;q_ >`'ƒqFcf;8WA@C^_ UC‰_hC7 ƒS_L>dcf>+S=_ƒPLS$~€Cq_‡_L>+S ==CA@ACq_W.e=eB~€>@G>;>@C=^c UmVF.=C'PLCGS==;>"__L;=XGCC= `*;A@;U$>@C ƒPLS~€C^_N_L>VS ==CAA@C " gK+j ]fA _LC`-WA@C ^F.C GCG> ƒPLS^ˆ>@C==C C‰__LC=^cf>+CAA@C`*CB=‰c Um F=XC ;W._LC=G‰C U C. inserm-00150018, version 1. UeGA+;7PQ;8c>VS$=XKCAA@C„` B`*C U^F.C  A@; A@;7PYC `e‰GS==;>"__L;=XGC UCq_1`eUC^G>+=_1C8cZUC A;uƒSƒqFA+;c>+S= UXF PA+C UC^_ ~;GcfC8FPN_ ƒPLS~€C^__L>+S ==XCA_ U;=_ A@; _€FP€ˆC=^F.C UCq_ G;=GCsPN_ D CX_ U>"_ƒ;7PL>dcfe‰_ U C PLCGS$==;>"__L;=G‰ChC='`;A@;U>@CEƒPLS$~€Cq_‡_L>+S ==CA@ACT_‡CA+S=†A@CEc"‹ƒChUChG;=GC7PGS=~4>+PL`*C=^cGC8c@cfC q‹qƒSqc2 ?‰_LC! D C^_ G;B=XGC7P_ A+Cq_ `†>@C8F PLCGS$==‰F_ _LS=^c*A@C^_ G;B=XGC7P_uPL;sPLC^_ US=^c'AV;v~€SP4cfC ;^_‡_LSG7>+;8cf>+S= ;8ˆ.CG F=C =^F.>"_‡;=GC _ƒeGB>@~> ^F.C C^_4cZW>@CB=OGS$==‰F.C UC‰_`*eUC‰G>+= _ _ƒeG>@;A>"_Leq_  A+Cq_`*e^_QSXc2 XeA|>VS `*C^_'ƒ A@C8FPQ;8F ;^_‡_LSGB>VeX_ A€m;`>@;=^cfC C8cxA+Cq_ G;=GC7PN_ =;q_LS„ _L>+=^F_L>@C= _ ;q_N_QS G>@e^_ ;8F K'ƒSXF_‡_L>+?7PLCq_ UC WS>_  =. PLC8ˆ$;=G CKUC‰_ZG;=GCsPN_hUm@S$P> Y >+=C`-FA c>@~;GcfS$P>VCBA+A@CuG‰S$`'`*CA@CG;=XG^CsPhU^F ƒSqF`'S= _QS$=‰cWC‰;8F.GSqFƒ `'S >+=_'W>@CB=OPLCGS$==‰F_ =^c€PQC wr! C8c1kr! UC^_*G;^_*UC G;=XG^CsPU^F ƒSqF`'S$= ;8c@c€P> WqF.;7WA@CX_  UCq_ C8 XƒS2_L>dcf>+S=_ ƒPLS~€Cq_N_L>+S==CAA@Cq_ _LC7PQ;B>@C=^c >+=UC`'= >"_QeX_ t > A@C =XS `-WPLC U C G;B=XG‰C7PN_ U^F ƒSqF.`'S = PLCGS$==^F_3CB=O`*;A;U$>@C ƒPLS~€CX_‡_L>+S ==XCBA@A@C ; =C8ccfCs`C=‰c';8FY`'C=^cfe ;8F{GSqFPN_*UC^_*UC7Pf=>?sPLC^_3;B==XeC^_QK Gqm@C^_4c ƒPL;8c€> ^F.CB`*C=^c F=>^F.C`*C=^c C7= PL;>"_LS= Um|F=C C7 ƒS_L>dcf>+S$=  A€m;`>@;=^cfCK A+Cq_ ;8Fc€PLC‰_ G;7=Ge7PLSY?7=C^_ƒqFA@`'S =;>+PLC^_ e8cf;7=^ccSXFs}LSqFPN_A+;7PfYCB`*C=qc!> Y=SPLe^_D ;EƒPLSƒSqP"c€>+S='UChG;q_PLCGS$==‰F_Cq_4c WC;8FGSXFƒ ƒAdF_'~f;> WA@C ƒSqFP-A+C^_<G;=GCsPN_'UC A@; ˆ.C^_‡_L>CxSXFOA+Cq_'A+CFGe`'>@Cq_ ;7P';7>+AA@C8FP_QK ƒA F_L>@C8FP_ G;7=Ge7PLSY?7=C^_ ;7ˆesPLe^_=C5~€>+YqFPLC=^c!ƒ;^_U;=_UCq_cf;WAC‰;8F †U Ch`*;BA@;U>@CEƒPLS ~€C^__L>VS ==CAA@CKGS`'`Chƒ;7P. /( ,!303(-,!)0 .(5 0, %&($,!(;87

(23) 3$. *"8($,!.( .3%&$8+ &70 (0 5 %&$.

(24) &( "87:($,;, )7

(25) 00(%'%)(, , 7

(26) 0 $ $, . $0 , *0 *

(27) &8(.  &3%&( .( 3( 0 *"5 ;87 8;:8(03( / %& , ( 317

(28) 5 "% ;( .($, 

(29) (10, 310"3187 0($, (+ 

(30) ($, . ( 303(6:

(31) *80  1*  %&(1*. .(, 5 %&.

(32) )(, 87:(

(33) ,-, &7

(34) 0"0(%&%&($, .* 8  5 ( ;01% (; .* 8  5 ( 

(35)  &37

(36) %&( .(,83+*"8' ,87

(37) 31)%&( (;*.  $%&(5 (10

(38) ;&8( 37

(39) 0 , *%' 1(=, *%)(9,8 ( . ( %!

(40) "#""$ &0-,% :&.

(41) i. HAL author manuscript. C8 $CB`'ƒA@C†A@C'G;U`> F`<K A@C<W$e7P‹AA> F.`'KSXFxA@C-~€S$PL`*;AUe q‹$UCKG^C^F>GS$=‰c€P> WqF.C'e7Y;A@C`C=‰c<A@;_LSqF_ PLCGS$==;>"__L;=G‰ChUC^_G;B=XGC7PN_ƒPLS$~€Cq_‡_L>+S ==CA"_ 4 i   MO;A+YPLe'A+Cq_E>+=G‰C7P€c€>dc"F.UC^_LK>+AC^_4c GC7P4cf;s>|= ^F.C-ƒAdF!_L>CFPN_E`'>@AA>@C7P‡_ UC†G;^_ UC'G;=GC7Ph_LS=^c U^F_ G1 ;^FC ;7==Xe^C bUC^_ C8 XƒS2_L>dcf>+S =_ ƒPQS$~€Cq_N_L>VS ==CAA@C^_'‚CX_ G;7=GC7PN_O_LS=^c UC ƒAdF_ GS=GC=‰c€PLe^_ U;7= _ A@Cq_. inserm-00150018, version 1. G;8cfesYSP>+Cq_1SXFˆXP >V?7PLCq_LKCcZGsS$=‰c€P> WqF.C=^c5US$=XG ;8F >+=eBY;A+>dcfeq_'_LSG>+;ACq_1UC `'SP4cf;7A+>dcfe C8c5Um>+=GB>@UC=G‰C UC^_ G;=GCsPN_ D;% C XƒS2_L> c>+S= ƒPLS$~€Cq_‡_L>+S ==CA@AC  UC^_ G;=Ge7PLSY?7=C^_ ƒPLe^_‡C=‰cfC C7= SXFc€PLC UC^_ ƒ;7P4c€>VG8FA@;7PL>dcfe‰_Tƒ;sPTPL;sƒƒS$P"c  UC^_Z~€;G8cfC8FP‡_-A+>@e^_1;8FOG‰S`-ƒS$P"cfC`'C=^c5CŽc5;8F `'SUC UC3ˆ>@C GS `'`*C A"C cf;8W$;GTSqFuA % ;BA+>@`C=‰cf;8c€>+S=6^D;% C7 ƒS_L>dcf>+S=C‰_4cCs=†Ye=e7PQ;BA>+=qˆSA+S$=‰cf;> PLCZC8cA+Chƒ A F__LSqFˆ.C=^c> Y =XS$PLeCTUCq_ c€PL;8ˆ$;>|A@A@C8FPN_GS$=XGC7PL=e^_#=3GS$=‰c€PLC7ƒ;7P"c€>@CK AVCTPL>_,^F2C-UC-G;s=G‰C7P;^_‡_LSG>+e -GCq_ C8 ƒS_L>dcf>+S = _ ƒC8FcNc€PLC PLCA+;8cf> ˆC`*C=^ch~€;GB>@A@CB`*C=^c ƒPLeˆC=^F.Kƒ;7PEF.=CueBA@>`*>|=;7c€>+S= UCq_-_€F W_€cf;7=GCq_ZA@Cq_hƒ A F_Z=SG> ˆ.C^_1C8c ƒ;7P F=C'U>`*>|=qFcf>+S= UCq_E=> ˆ.C;8F xU&% C7 ƒS_L>dcf>+S$=uYPGC 'Am@;`eA@>+S$PQ;8c€>+S= UC^_ƒPQSXcfCGNc€>+S=_ GS A+A@CG8cf> ˆCq_ C8c >+=U$> ˆ.>@U^F.CBA@A@C^_1C8c UC^_Z`'S UCq_ZSƒe7PL;c€S> PLC^_‚C^_1G;7PL;G7cfe7Pf>_4cf>^F.Cq_}QF_€c>+~>@C=^c ^F!m@S$=xƒS$P4cfC†F= >+=^cfesP,8c ƒ;7P4c€>VG8FA@>@C7P ;8F G;=GC7P_ UmSPL> Y>|=C ƒPLS~€CX_‡_L>+S ==XCBA@A"C U^F ƒS$>+=‰c UC{ˆF.CbUCbA; PLCG CsPLG CbCc A@; ƒPLe8ˆ$C=^cf>+S$='. 5 - / [ T] 7Ezh‚ MvS$=XS$YPQ;7ƒ0 _ S= c2 XC (ˆ.;A F.;8cf>+S$= S~ ‚;PLG>+=SYC7=>@G{zh>"_ 4_ cfS :ZF`';= _QK†l1S A  [ ii& ]=‰cfC7P=;c€>+S$=;A&7hYC=G7‹*~€S$Pz C^_QC;7PLG 'S='‚;7=GC7P8\BD(‹XS=6 wR F.> Y=S=   K t;=UqPQC8c . qD C^_ C7 ƒS_L>dc>VS = _ ;8F uƒP‡SU^F>dcL_G;B=XGe7PLSY?7=XCX_  !PLC`'>@?7PLCq_ht‹=‰c5 X?^_LCq_. =

(42) wi&"[ „ F>+A@ACcwrr. 6l->+=GC=‰chzhKŠ1;8Fƒƒ>|=C= (KS$> 404;=XCB= ŽK CUC7P_LC= :<K-SqF=qY z K  Š1SYC8ˆ>+=;q_TM#‚ 75z -K _‹_€cf?`'C>+=^cfC7PL=;c>+S=;AU&% >+=~€S$PL`*;8cf>+S$= _4FPhA % C XƒS2_L> c>+S= ƒPLS~€C^__L>+S ==XCBA@A@C;8F ;7YC=^cL_ G;=G‰e7PQS$Y?7=XC^_.

(43) p. HAL author manuscript. C7= FPLSƒC!7z e^_4F.Adcf;8cL_ UC^_C^_€c€>|`*;8cf>+S=_ƒSqFPA+; yPL;=G‰CEƒC7=XU;=^cAVC^_;==e‰C^_h[sppr„s[spp06q‚;1 >@C7PN_ U C =SqcfC^_US GF`'C=^cf;> PLCq_„ :Z‹Y >@?=ChC8c_LeGFP>dcfehU^F-c€PL;ˆ;7>@A„ T [sjgK&C c"Pf>|`*Cq_4c€PQC[sppp kt>+C`>@;8c€‹G 4 >  K zh>@G ;7PQU _LS=†D Ktqc€PL;7>+~(Š1K D ;8c€PLC>+AA@C . K.D ; 40 ;B=>z K‚;B`'ƒWCAAtK z SXF_‡_LC;8FuMv‚K. S$~€~fC8c"cf;; 7D >_4cf>+=qY*S GG8Fƒ;8c€>+S=;AG‰;7PLG>+=SYC= _ =qˆ>+PNS= :<C;Adc2 C7PN_fƒCG8c ‰wrrqk  [ [w/7[ s \"[kkj„ p . inserm-00150018, version 1. & ;1 ` t!:<K A+;>+P 7 nTGG8Fƒ;8c€>+S=;AG;=XGC7P;`'S =Y<Œ<S`'C=\BŒ XC7PLC ;7ˆC Œ<CEWCC=';=UTŒ XC7PLCh;7P‡C Œ<CEYS$>+=qY 7Z`  ]=UTM CU6‰wrr0  kk!\ g„j g6]`-WC7PL=S=.  _4c€>+`*;8c€>+S= U^F =S `-WPQCuUCuG^;‰_ZUC GC7P4cf;7>+= _1G;=XGC7PN_Z;c"c€P> WqF.;7WA@CX_ uUC^_Z~;GcfC8FPN_. ƒPLS~€C^_N_L>VS ==CA"_*C= yPL;=XGC!]= _€c> c"FcZUC ˆ$CB>+A@AC _L;=>dcf;>+PLCK(:'esƒ;7P4cfC7`'C=‰c'_L;7=‰cfe c"PL;ˆ;>A+Kwi ƒKwrr0.  ;7PYC;WA@CT_€FP ŒTŒZŒ  >+=qˆ_ _L;=^cfC  ~"P . cfe7AVeG. j6zh;sƒƒS$P"c UCA+; ‚S`'`>"__L>+S = >+=_4cf>dc"F.eCƒ;7PZA % ;7P€c€>+GA"C†D[sjg„4w U^F GS UCuUCuA+; teG8FPL>dcfe _QS G>@;ACK F.>+=-wrr&. i&Š1;^_W>@„  CB=;‰_N_LSqF.A|>l dK]L`-WC7PL=S=.  K ]4Œ<;NcL_4FWS .  K  F>_‡_LS= ‚  KRTSA+UqWC7PfY M ‚S=~"PLS=^cf;8c€>+S=. UC^_<G;=G‰e7PLSY?7=C‰_';7ˆ.e7PLe^_<C= `>A@>@C8F UC c€PL;8ˆ;>+AhCc1UC^_Tcf;8WA@C;F vUC `*;A;U$>@C^_1ƒPLS ~€C^__L>+S==CAA@C^_ ]=_4cf>dc"Fc. UC. ˆC>+AA@C. ŒZŒTŒ d>+=qˆ_ _L;=^cfC! ~"P; . _L;=>dcf;>+PLCK :<e7ƒ;7P4cfC`'C=‰c. _L;s=^cfe. c€PL;8ˆ;>+A+K wrr.  ;sPYC;7WA@C _4FP. cfeA+eG.

(44) [sr. HAL author manuscript. ;8WA@C;8F [ .  ƒS_L>dcf>+S= _'ƒPLS ~€C‰__L>+S ==CA@AC‰_uGA@;^__LeCX_'ƒ;sPA@C ‚ ]€zh‚ GS$`'`*C G;=XGe7PLSY?7=Cq_'ƒSqFP. A€m S`†`*C 

(45) .       . !#"$%$&'(&)$!*,+.- "$%- +$*/+. inserm-00150018, version 1. !#"$%$&'(&)$!*G+9" 4 - >/& 0#"1+9+#- I>/&+JB%&LK?"- + P - 4 - 6&(6>Q- +*/%4 4 - $& RS'T- $?&+ )>@"'U*V- W1?&+ $)[%<*4 'T- $!&)] RS>,+&)$- 6. XFK?&)$Y- B- $!&3. )'8- $!"O/Z)O,B - [%<7)$4 &!3. RS>,+7)$- 1>,&_B&L`4 4 - 1)' a7)>@4 4 - 1' Mb<%>@"'2&L<?&c!N)4 &)$!* dG- 6#e&4#X,6&H>,*/%- $?+J6"'2[")+97+f] M B)'T- 1' gS1- 4 &+JB)&2+f6!<%- +*@& h "1?B>@"$+J&*GK>,- +iB%&L<?"1%- 4 4 & P 1- &+ gS1- 4 &+i'T- $!7)>@4 &+3j[&)12"1k$!"$_>/D@D/- $7&!+ a&)$YI)$& Mb<4 ">=1>/&_B&2N)- $!)4 & m")>='(%4 B)7)<B)& a- +X,6#<4 ")>/")'27!*F<!4 ]=7!*F<&> n c#B&_Bo 7*F<4 I)$!& \3@p3@q!3sr2t MGuGuvX=B- "!c- $&] a)>/"1%- 4 4 )>,B+iBo 6#- B)&!+DC">w*/+J6")$?*/&)$!)$*jB)&T4 o !6- B%&_+x1%4 D/1>V- W1!& h Y.'."1!*,)>@B)& tj)K`- +'.&k[!++- D. 0#"1'2"$!354 &)1!67)'8- &+93:"%+3;*=<?>@"!ACB&3ED@"- &3 )1*F>@&+ 0#&)1!3G'.74 H$?")'(& M !N)- */7#+.$+9")O/+!- $)1!+!- &)$$&+ 0#"1'2"$ \)O &++- & ^ 0#&)1 0#"1'2"$ 0#"1'2"$ 0#"1'2"$ 0#"1'2"$ 0#"1'2"$ M !N)- */7#+.$+9")O/+!- $)1!+!- &)$$&+ 0#"1'2"$ 0#&)1 0#&)1!3G[!"1)'U"$!3N#&++- & 0#&)1!3G[!"1)'U"$ 0#&)1!3G[!"1)'U"$!3N#&++- & lf&)1?6f7)'8- & m"- &_X=)$`- "+f>,6f"'.&)] d +f"[<)>)$!c 0#"1'2"$ lf&)1?6f7)'8- & tb"1+J6)$!6&H>,+J6"'2K- $7!+ lf)>wH$!c!3S[!"1)'."$ 0#"1'2"$!3NH"- &+J)>,7H>w"O,B- `%&#+*V- N&+J+1)[?7H>Q- &)1%>@&+ 0#"1'2"$.

(46) [[. HAL author manuscript. ;8WA@C;8F w „ !PLS$~fC^_‡_L>+S =_ SXF >+=U^F_€c€P >VCX_ GA@;^__LeCq_ ƒ;sP A+C ‚]4z ‚ GS`'`*C G;=Ge7PQS$Y?7=C‰_ ƒSqFP A€m S`†`*C. inserm-00150018, version 1. bV )!   Gj F R

(47) 4 1'T- $- 1' XV[>,"B16*V- "$2B ] RS1)>,H'T- $!&LX=D@)K>Q- 6!*V- "$8 B ] `%&)$!*/LX=D@)K>Q- 6!*V- "$] M ")1*@6#<?"1!6.XV- $B1+*=>=- &_B)1%] Mb<)>/K?"$_X,`)+7)- D=- 6!*V- "$] M "e&_XV[)>@"%B1!6*V- "$_B&)] m"$B&)> - &_B&_DC"$*@&_&#*GB 6!- &)> Mb<)1?+f+1)>,&#+X=Ds)K>Q- 6!*V- "$_&!*S>,7)[>/!*V- "$)] gb7)'.*=- */&LX,&!c#*F>,!6f*Q- "$_+9"1?*s&)>,>/- $?&_N&#6.&c)[!")+!- *V- "$_1k>@B"$%]

(48) F+"[>,")[)$!"4#X=D@HK%>=- 6*V- "$2B)&T4 ]XF[%>@")67B% 7 k4 !6- B&LD">@*=] &)1%K4 &#+iX=D@)K>Q- 6!*V- "$)]G&*j7)K!7)$- +*,&H>Q- & 0#&- $!*F>/&!+.

(49) [w. HAL author manuscript. ;8WA@C;8F   S`-WPLChUC c€PL;ˆ;>+AA@C8FPN_C7 XƒS2_Qe^_C7=-yPL;=XGC  ^F.CA^F.C‰_G;=G‰e7PLSY?7=XC^_. inserm-00150018, version 1.  C  .   

(50)  . j . RG>/+9&)$- 6 a&)$?YfI)$?& a7)>w4 4 - 1' a)>,"1%- 4 4 )>/B+Bo 6!- B%&#+DC">@*/+J6")$*/&)$!)$?*bB%&k4 o #6?- B)&_+1%4 D/1>Q- W1!& MB)'k- 1' Mj<4 ">F1>,&_B&(N%- $H)4 & Mj<)>@"'(&_<&cH!N%4 &)$!* m")>='2)4 B)7)<B)& gHB)>,"6>FK%1>/&+ )>@")'2*F- W1?&#+.[!" 4 H696#4 - W)1&+ dG- 6#e&4 n c!HB&_Bo 7*=<4 I)$!& 0!"1?++!- I>,&+JB)&_K"- + P - 4 - 6&26>V- +*/%4 4 - $?&. \. Z. q ! \ . Z \%\ r ? r  p ! \  ! !p. r .  . Z)r O O \r O ! r  ) p  \ ) r  O pr \)q.

(51)

Références

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