• Aucun résultat trouvé

Etude physiopathologique de modèles murins de leucodystrophies dysmyélinisantes et approche thérapeutique

N/A
N/A
Protected

Academic year: 2021

Partager "Etude physiopathologique de modèles murins de leucodystrophies dysmyélinisantes et approche thérapeutique"

Copied!
339
0
0

Texte intégral

(1)Etude physiopathologique de modèles murins de leucodystrophies dysmyélinisantes et approche thérapeutique Bérengère Depiets. To cite this version: Bérengère Depiets. Etude physiopathologique de modèles murins de leucodystrophies dysmyélinisantes et approche thérapeutique. Médecine humaine et pathologie. Université d’Auvergne - ClermontFerrand I, 2012. Français. �NNT : 2012CLF1MM04�. �tel-01077895�. HAL Id: tel-01077895 https://tel.archives-ouvertes.fr/tel-01077895 Submitted on 27 Oct 2014. 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) 

(3)    . 

(4)  +

(5) 

(6)      .  

(7)    

(8)  8#?-0#0$ .  0=1$,2=$:?,(4$01(2=#?

(9) 34$0&,$ -30*?-!2$,2(-,#3&0 #$#$-"2$30#?,(4$01(2= .="( *(2= =,=2(/3$$2'61(-*-&($ -32$,3$ .3!*(/3$+$,2 *$ 4$,#0$#( )3(,. )" '"  .       

(10) .     

(11) 

(12)    . 0=1(#$,2 .  0

(13) * (,

(14) .  ..-02$301 .  0 2' *($

(15) 

(16)   0 0 '(+

(17) 

(18)   060(*. $+!0$1 .  0=*(,  . (0$"20("$#$2'<1$  0 #(*$ 

(19) .   7 '61(-. 2'-*-&($$22'=0 .($1#$1+ * #($1#3"$04$ 3#$*?$,% ,2 9 /3(.$7 (,2$0 "2(-,#$1"$**3*$1&*( *$1 3"-301#3#=4$*-..$+$,2,-0+ * 2 . 2'-*-&(/3$ #31612<+$,$04$35"$,20 * 9.

(20)

(21)

(22)

(23)

(24)

(25) !"$!"+% 1).  U ,BSMCIJ;NBIFIAC??NNBeL;JC?M>?MG;F;>C?M>O=?LP?;O>?F‚?H@;HN Y CL?=N?OL $62??2&''"' $mJCN;F.I<?LN ?<Le  <IOF?P;L> /eLOLC?L ,;LCM. "#%%"& $?9.6;' &$)$ *?OLI IF %*/!.) 1 (;<IL;NICL?>?,B;LG;=IFIAC?)e>C=;F? ";=OFNe>?)e>?=CH? ,B;LG;=C? JF;=?$?HLC OH;HN , F?LGIHN "?LL;H>?>?R. ?".A5.962!"&#" $552?052B?"&' & ?HNL?>?.?=B?L=B??H*?OLIM=C?H=?M>?(SIH. 1).%*/!.) 1HCP?LMCNe(SIH.  ;P?HO? 0IHS#;LHC?L. (SIH?>?R. ??.56:"(#)!'!& $5 52?052B?"'&! &. ?HNL?>?.?=B?L=B? >?F%HMNCNON>O?LP?;O?N>? F;)I?FF?!JCHCdL? .%) 1HCP?LMCNe,C?LL??N);LC?OLC? ,;LCM %*/!.)1). / *./ 1). <>>?F$mJCN;F ,;LCM=?>?R. $?F?69#-($)$ ! (;<IL;NICL?).#)U);F;>C?M.;L?M#eHeNCKO??N )eN;<IFCMG?Y 1HCP?LMCNeIL>?;OR/?A;F?H 1".>?M/=C?H=?MGe>C=;F?M LO?(eI/;CAH;N ;M? IL>?;OR?>?R. $?#1692#'$ )("),$)$ ?HNL?>?Le@eL?H=?>?M(?O=I>SMNLIJBC?M /?LPC=?>? U *?OLIFIAC?,e>C;NLCKO? ?N);F;>C?M)eN;<IFCKO?M Y $mJCN;F.I<?LN ?<Le <IOF?P;L>/eLOLC?L  ,;LCM =?>?R. %*/!.)1).U ,BSMCIJ;NBIFIAC??NNBeL;JC?M >?MG;F;>C?M>O=?LP?;O>?F‚?H@;HN Y !KOCJ?U %HN?L;=NCIH>?M=?FFOF?MAFC;F?M;O=IOLM>O >eP?FIJJ?G?HNHILG;F?NJ;NBIFIACKO?>OMSMNdG? H?LP?OR=?HNL;F Y. ?!T96;.#) $5.?: $5 %*/!.) 1). U ,BSMCIJ;NBIFIAC??NNBeL;JC?M>?MG;F;>C?M>O=?LP?;O>?F‚?H@;HN Y !KOCJ? U %HN?L;=NCIH >?M =?FFOF?M AFC;F?M ;O =IOLM >O >eP?FIJJ?G?HN HILG;F ?N J;NBIFIACKO? >O MSMNdG?H?LP?OR =?HNL;F Y ";=OFNe>?)e>?=CH? ,B;LG;=C?  JF;=?$?HLC OH;HN , F?LGIHN "?LL;H>=?>?R. .

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

(28) AB12=5F@6<=.A5<9<46>B212:<1S92@:B?6;@1292B0<1F@A?<=562@ 1F@:FT96;6@.;A2@2A.==?<052A5T?.=2BA6>B2 &T@B:T (?M GON;NCIHM >O AdH? >?M JLINeIFCJIJLINeCH?M %!%

(29)  =I>;HN >?M JLINeCH?M MNLO=NOL;F?M G;D?OL?M >?F;GSeFCH? >OMSMNdG?H?LP?OR =?HNL;F,(, ?N ) MIHNL?MJIHM;<F?M>‚OH MIOM ALIOJ? >? F?O=I>SMNLIJBC?M >SMGSeFCHCM;HN?M FCe?M [ F‚4

(30)  (; @ILG? F; JFOM MePdL?  F; G;F;>C?>?,?FCT;?OM )?LT<;=B?L,)  CH>OCN?JLCH=CJ;F?G?HNJ;L>?M>OJFC=;NCIHM>OAdH? =IH>OCN[OH?BSJIGSeFCHCM;NCIHG;D?OL?N;H>CMKO?F;@ILG?F;JFOMGI>eLe? F;J;L;JFeAC? MJ;MNCKO? >? NSJ?  /,#  CH>OCN? J;L >?M GON;NCIHM HIH M?HM IO >?M >eFeNCIHM >O AdH? =IH>OCN [ OH? GSeFCH? G;F =IGJ;=Ne? ?N OH? >eAeHeL?M=?H=? ;RIH;F? N;L>CP?

(31)  ? NL;P;CF >? NBdM?JILN?MOLF;=;L;=NeLCM;NCIHJBeHINSJCKO?>?MIOLCMNL;HMAeHCKO?MG^F?MJLeM?HN;HNOH? CHP;FC>;NCIH >O AdH? %:>

(32) MIOLCM ,FJ HOFF  ;CHMC KO? >?M @?G?FF?M BeNeLITSAIN?M JIOL =?NN? GON;NCIH?NMOL?RJLCG;HNF?AdH? %:>

(33) MIOLCM,(+ GI>dF?M>?MGdL?MNL;HMG?NNLC=?M>? =?M G;F;>C?M

(34) 1H? eNO>? FIHACNO>CH;F? >O =IGJILN?G?HN >? =?M MIOLCM ; eNe Le;FCMe? ?N ; J?LGCM>?G?NNL??HePC>?H=?=B?TF?MMIOLCMG^F?M,FJHOFFF‚;JJ;LCNCIH>?NLIO<F?MGIN?OLM. M?HMCNC@M ?N =IAHCNC@M  KOC IHN JO ?HMOCN? fNL? L?FCeM [ >?M ;HIG;FC?M >‚?RJL?MMCIH  >? G;LKO?OLM ;MNLI=SN;CL?M IO GC=LIAFC;OR ?N >? H?OLIJ?JNC>?M CGJFCKOeM >;HM F; >IOF?OL ;O HCP?;O>?F;GI?FF?eJCHCdL? >?G;LKO?OLM;S;HNOHLmF?>;HMF?MJLI=?MMOM=IAHCNC@M>;HM F?=?LP?;O?NHIN;GG?HN>;HM=?LN;CH?MLeACIHM>?F‚BCJJI=;GJ??N  [ >?M;FNeL;NCIHM>?M PCN?MM?M >? =IH>O=NCIH H?LP?OM?

(35)  B?T F?M @?G?FF?M GONe?M %:>

(36)  F?M ;HIG;FC?M =IGJILN?G?HN;F?M M?G<F?HN FCe?M ;O AeHINSJ?  ;P?= F? >eP?FIJJ?G?HN >? MSGJNmG?M OHCKO?G?HN=B?TF?MGdL?MJILN?OM?M>?GON;NCIHGI>eLe?

(37) ?JOCMKO?FKO?M;HHe?M OH?HM?G<F?>?>IHHe?MePIKO?HNOHLmF?>?F;MO<MN;H=?<F;H=B? ?N HIN;GG?HN F; GSeFCH?  >;HM F?M @IH=NCIHM =IGJILN?G?HN;F?M ?N =IAHCNCP?M

(38)  (?M LeMOFN;NM I<N?HOM;O=IOLM>?=?NL;P;CF=IH@CLG?HNF‚CHNeLfN>?MMIOLCM,FJHOFFJIOLGC?OR=IGJL?H>L? =? LmF?

(39)  ? JFOM  F?M HIG<L?OM?M MCGCF;LCNeM C>?HNC@Ce?M ?HNL? F?M GI>dF?M ;HCG;OR ?N F; J;NBIFIAC?BOG;CH?J?LG?NN?HN >‚?HPCM;A?L F‚ONCFCM;NCIH >? =?MGI>dF?MJIOLF‚eP;FO;NCIH>? HIOP?FF?M MNL;NeAC?M NBeL;J?ONCKO?M

(40)  *IOM ;PIHM ;CHMC eP;FOe F‚?@@C=;=CNe >‚OH H?OLIF?JNCKO? ;NSJCKO?MOLF?MNLIO<F?M=IGJILN?G?HN;OR>?MMIOLCMG^F?M,FJHOFF

(41). !<A@09T@  %!%

(42) JLINeIFCJIJLINeCH?M F?O=I>SMNLIJBC?M >SMGSeFCHCM;HN?M  G;F;>C? >? ,?FCT;?OM )?LT<;=B?L  J;L;JFeAC? MJ;MNCKO? >? NSJ?   GI>dF?M ;HCG;OR =IGJILN?G?HN. eNO>?JBSMCIJ;NBIFIACKO?

(43). .

(44) $.A5<=5F@6<9<460.9 @AB1F<3:<B@2:<129@<31F@:F296;.A6;4 92B8<1F@A?<=562@.;1A52?.=2BA60.==?<.05 /@A?.0A )ON;NCIHM I@ NB? JLIN?IFCJIJLIN?CH A?H?  ,(,  =I>CHA NB? G;DIL MNLO=NOL;F JLIN?CHM I@ NB? =?HNL;F H?LPIOM MSMN?G  ,(, ;H> )  ;L? L?MJIHMC<F? I@ MIG? 4 FCHE?> >SMGS?FCH;NCHA F?OEI>SMNLIJBC?M

(45)  0B? GIMN M?P?L? @ILG  NB? ,?FCT;?OM )?LT<;=B?L >CM?;M? ,)   >O? NI A?H? >OJFC=;NCIHM  =;OM?M ; G;DIL BSJIGS?FCH;NCIH QBCF? NB? GI>?L;N? @ILG  NB? MJ;MNC= J;L;JF?AC; NSJ?  /,#  >O? NI HIH M?HM? GON;NCIHM IL A?H? >?F?NCIHM  F?;>M F?;>CHA NI OHJ;=E?> GS?FCH ;H> F;N? ;RIH;F >?A?H?L;NCIH

(46) 0BCM NB?MCM QILE @I=OM?M IH JB?HINSJC= =B;L;=N?LCT;NCIHI@NL;HMA?HC=G;F?GC=?QCNB %:>

(47) CHP;FC>;NCIH,FJHOFFGC=? NIA?NB?LQCNB B?N?LITSAIOM @?G;F?M @IL NBCM GON;NCIH ;H> IP?L?RJL?MMCHA %:>

(48) ,(+ GC=?  GI>?FM I@ =;LLC?LGINB?LMI@NB?M?>CM?;M?M

(49) FIHACNO>CH;FMNO>SIHGC=?<?B;PCILQ;MJ?L@ILG?>;H> ;FFIQ?>NIBCABFCABNCH,FJHOFFG;F?GC=? NB?IHM?NI@GINIL M?HMCNCP?;H>=IAHCNCP?>?@?=NM. NB?H FCHE?> NI ?RJL?MMCIH ;<HILG;FCNC?M I@  ;MNLI=SNC= IL GC=LIAFC;F G;LE?LM ;H> H?OLIJ?JNC>?M CHPIFP?> CH J;CH@OF JLI=?MM?M CH MJCH;F >ILM;F BILH   G;LE?LM CGJFC?> CH =IAHCNCP? JLI=?MM?M CH <L;CH ;H> ?MJ?=C;FFS MIG? BCJJI=;GJOM L?ACIHM   ;FN?L;NCIHM I@ H?LP? =IH>O=NCIH P?FI=CNC?M

(50)  %H ,FJ GON;N?> @?G;F?M  <?B;PCIL;F ;<HILG;FCNC?M M??G NI <? L?F;N?> NI A?HINSJ?  QCNB >?P?FIJG?HN I@ MSGJNIGM IHFS CH @?G;F?M =;LLSCHA GI>?L;N? GON;NCIH

(51) /CH=? @?Q S?;LM  >;N; MOAA?MN ; LIF? I@ QBCN? G;NN?L  ;H> J;LNC=OF;LFS GS?FCH  CH =IAHCNCP?;H><?B;PCIL;F@OH=NCIHM

(52) .?MOFNMI@NBCMMNO>S=IH@CLGNB? CHN?L?MN I@,FJHOFFGC=? NI <?NN?L OH>?LMN;H> NBCM LIF?

(53)  "OLNB?L  MCGCF;LCNC?M C>?HNC@C?> <?NQ??H ;HCG;F GI>?FM ;H> BOG;HJ;NBIFIAS ;FFIQNI=IHMC>?LNB?M?GI>?FMNI;MM?MMH?Q NB?L;J?ONC=J?LMJ?=NCP?M

(54) 3? NBOM;MM?MM?>NB??@@C=C?H=SI@;NSJC=;FH?OLIF?JNC=IH,FJHOFFGC=?<?B;PCIL;F;FN?L;NCIHM

(55). 2FD<?1@ %!%

(56)  JLIN?IFCJIJLIN?CH  >SMGS?FCH;NCHA F?OEI>SMNLIJBC?M ,?FCT;?OM )?LT<;=B?L >CM?;M?. /J;MNC=J;L;JF?AC;NSJ? ;HCG;FGI>?FM <?B;PCIL J;NBIJBSMCIFIAC=;F MNO>S

(57). .

(58) $(&! % )  BPA>C>=8=4 "%  X0<8=>

(59) 7H3A>GH<PC7H;8B>0I>; ?A>?8>=0C4 (  20=0DG8>=8@D4BB4=B81;4BM;[02838CP )%  03P=>B8=4CA8?7>B?70C4 (0=C8B8;4=24A4=70=24A4;4<4=C 0B?A  2>=C02C8=0BB>280C43?A>C48=   #  2>=CAU;4B8=7818C4DAB3855DB=>2824?C85B #% [

(60) [2H2;82=D2;P>C834

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

(62) "$ <H4;8=$;86>34=3A>2HC4;H2>?A>C48= "'  502C4DAAP6D;0C4DA3D6O=434;0<HP;8=4 "H)   "H4;8=CA0=B2A8?C8>=502C>A  #  =>A03AP=0;8=4 #  #02PCH;0B?0AC0C4 #  =4AE46A>FC7502C>A #"  #<PC7H;0B?0AC0C4 #'  =4DAP6D;8=4 #)

(63)  =4DA>CA>?78=4

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

(65)  7>A<>=4C7HA>R384==4CA88>3>C7HA>=8=4 )  )A4<>AC0G80F8C74=CA0;H?><H4;8=0C8>= )"+  )748;4A[B<DA8=44=24?70;><H4;8C8BE8ADB )'% %,.!&%!(,*1+)%*!%+)'+&)'&+%+!#2 )'%+  AP24?C4DA8>=>CA>?8@D4E0=8;;>R34+'. ))G CPCA>3>C>G8=4 *%'  D=5>;343?A>C48=A4B?>=B4 +#  E8C4BB4342>=3D2C8>==4AE4DB4 ..  502C4DA34CA0=B2A8?C8>=.8=6.0=6. /5?   ?A>CP8=4M3>86CB34I8=2 . .

(66) %!$  &$!'&!   G&'!$"#'. . . %*%& $(') &$ .  %$"&!  &!#'' %  .  :%7' #   $&##7'!%!5)    *%)*)3%!%*  .  !"$& &&! ' %     *,*+%)!*+#*%,)&%*    *,*+%#%    0 !4B0G>=4B   1 !4B24;;D;4B6;80;4B

(67)   !4BP?4=3H<>2HC4B

(68).   !4B24;;D;4B34;0<82A>6;84 

(69). 

(70)  !4B0BCA>2HC4B

(71)    !4B>;86>34=3A>2HC4B 

(72)   0 P58=8C8>=

(73)   1 "P20=8B<4B34<0CDA0C8>=34B$!B

(74)   2 "P20=8B<4B34<>AC34B$!B  .  ! &! %' % 

(75).  &%+!&%$&+)!   &%+!&%*%*&)!##   0 !4BB4=BB?P2858@D4B  1 !0B><4BC7PB84 ;420B?0AC82D;84A34;03>D;4DA    "P20=8B<4B?PA8?7PA8@D4B8<?;8@DPB30=B;03>D;4DA   0 !4B581A4B=>2824?C8E4B    1 !4BAP24?C4DABP;P<4=C08A4B   2 !4B20=0DGE>;C0643P?4=30=CB     "P20=8B<4BB?8=0DG8<?;8@DPB30=B;03>D;4DA !4BE>84B0B24=30=C4B   0 #4DA>=4BB?8=0DG8<?;8@DPB30=B;03>D;4DA    1 !4B508B240DGB?8=0DG   

(76)  "P20=8B<4B24=CA0DG8<?;8@DPB30=B;03>D;4DA .   "P20=8B<4B342>=CAU;434;03>D;4DA 

(77)  !4BBH=3A><4B3>D;>DA4DG   0 !03>D;4DAJ ?7HB8>;>68@D4 K   1 !03>D;4DAJ 8=5;0<<0C>8A4 K   2 !03>D;4DAJ =4DA>?0C78@D4 K   <?;820C8>=34B24;;D;4B6;80;4B30=B;03>D;4DA    G?;>A0C8>=B5>=2C8>==4;;4B .  &%+!&%&%!+!-   0 !0<P<>8A4    !4B3855PA4=CBCH?4B34<P<>8A4    0 !0<P<>8A4B4=B>A84;;4  

(78)  1 !0<P<>8A4M2>DACC4A<4  

(79).

(80)  2 !0<P<>8A4M;>=6C4A<4  

(81)   %A>24BBDB3[02@D8B8C8>=4C34A4BC8CDC8>=  

(82)  !4BBCAD2CDA4B2PAP1A0;4B8<?;8@DP4B>DBHBCO<4B34<P<>8A4   

(83) 0 !420B?0AC82D;84A3D?0C84=C"   

(84) 1 !428A2D8C78??>20<?8@D4  

(85) 2 !428A2D8C0<H630;84=  

(86) 3 <?;820C8>=3DBCA80CD<4C34B60=6;8>=B34;010B4   

(87) 4 <?;820C8>=2>AC820;4 

(88) 

(89) 5 =APBD<P     "P20=8B<4B24;;D;08A4B34;0<P<>A8B0C8>=   0B4B<>;P2D;08A4B34;0<P<>8A4   1 ![0=G8PCP     (CAD2CDA4B2PAP1A0;4B4C28A2D8CB34;[0=G8PCP    0B4B<>;P2D;08A4B34;[0=G8PCP  .  0 !46;DC0<0C44C;4  .  1 !4B<>=>0<8=4B  

(90)  2 !4B=4DA>?4?C834B    *G '%*%& $(') &$& %"&!!    &!    !$ %&! *     *!%+)%&*   *')%&*+",.+')%&*    *%9,*%-!)   !"!%&! * ' %    *#!'!*#$/7#!%    *')&+7!%*#$/7#!%    **$#!%+)##,#!)#$/7#!%+!%+7)+!&%$$)%!) .  !$&! * '!'$%'(!"" &    $!*     &%,+!&%#:!%#,.%)-,.  

(91)  )&++!&%#:.&%+!%+)+!&%*##,#!)*    "&!!% '$!!#'%& !% %'%&      + &#&!*-++!%+')!$!+!-#*,*+%#%    0 %0C7>;>684B6P=PC8@D4B;4B;4D2>3HBCA>?784B     !4B;4D2>3HBCA>?784B7H?><HP;8=8B0=C4B .   !4B;4D2>3HBCA>?784B3P<HP;8=8B0=C4B  1 %0C7>;>68402@D8B4;420B34;0B2;PA>B44=?;0@D4B 

(92)   (2;PA>B44=?;0@D4B4C3>D;4DA   (2;PA>B44=?;0@D4B4C2>6=8C8>=   + &#&!* %,)&77%7)+!-* !$'#!(,%+ ,% ++!%+  # *,*+% #%  . 0 !0B278I>?7AP=84  1 !0<0;03843[;I748<4A   2 !0<0;038434%0A:8=B>=  3 >=2;DB8>=  . .

(93)  E  %"$!&G!"!"$!&G %&%%"&! %! &! %  "*! #' %"$!&!"!"$!& %   %&$'&'$'  ""   "$!'&%N)"$%%! '  ""   +),+,)+*/%+ 5*   !*+)!,+!&%*'+!##:.')**!&%*')&+7&#!'&')&+7!%*    .')**!&%*')&+7&#!'&')&+7!%*,&,)*, 7-#&''$%+   7,#+!&%#:.')**!&%    ! &! %!!#'%  ""    "&!!%%'   ""    + &#&!*+%+#: &$$#*'+ !* 

(94) 0 !0<0;038434%4;8I04DB"4AI10274A%" .  1 !0?0A0?;P684B?0BC8@D434CH?4 (%    *'+ !**$$* 7+7)&0/&+*   *$&5#*%!$,.  

(95) 0 !4B<DC0=CB=0CDA4;B     !4BB>DA8B<DC0=CB=0CDA4;B     !4BA0CB<DC0=CB=0CDA4;B

(96) 

(97)  !4B<DC0=CB=0CDA4;B3[0DCA4B4B?O24B

(98)

(99) 1 !4B<>3O;4B<DA8=BCA0=B6P=8@D4B

(100)

(101)   !4BB>DA8B4C;4BA0CBBDA4G?A8<0=C%;? >D%!$ 

(102)

(103)   !4BB>DA8B0E428=02C8E0C8>=3D6O=4%;? >D%;?=D;; 

(104)  

(105)  !4BB>DA8B4G?A8<0=C" B4D; 

(106)    !4BB>DA8B4G?A8<0=CD=A0C8><>3858P34%!%" 

(107)  2 !4B<>3O;4B34<OA4B7PCPA>IH6>C4BCA0=B<4CCA824B34%;??0C784B !&%

(108) &$()"$ & <>3-6/ O/-2+83=7902C:/<=/8=3>3@3>C>9>2/<7+6=>37?633873-/A3>2./6/>39890>2/ 7+49<7C/638:<9>/38P   %APB4=C0C8>=4C<PC7>3>;>684  .  'PBD;C0CB4C38B2DBB8>=    >=2;DB8>=4C?4AB?42C8E4B  + AC82;4   <>3-6/ O9>9<,?>+6=9-9183>3@/./0/->=3873-/./6/>/.09<>2/7+49<7C/638:<9>/38P    %APB4=C0C8>=4C<PC7>3>;>684    'PBD;C0CB4C38B2DBB8>=    >=2;DB8>=4C?4AB?42C8E4B  + AC82;4  . .

(109) <>3-6/ O00/->90+8/?<96/:>3-></+>7/8>98+,89<7+6,/2+@39<38.?-/. ,C6+-590""  >2/7+49<7C/638:<9>/3890-/8><+68/<@9?==C=>/7P    %APB4=C0C8>=4C<PC7>3>;>684    'PBD;C0CB4C38B2DBB8>=    >=2;DB8>=4C?4AB?42C8E4B  + AC82;4   <>3-6/

(110) O9183>3@/+8.=/8=3>3@/+,89<7+63>3/=382/>/<9DC19?=0/7+6/73-/6+-5381"" >2/7+49<7C/638:<9>/3890-/8><+68/<@9?==C=>/7P    %APB4=C0C8>=4C<PC7>3>;>684  

(111)  'PBD;C0CB4C38B2DBB8>=  

(112)  >=2;DB8>=4C?4AB?42C8E4B  + AC82;4   ! '%! G G$   $L0L</8-/=,3,6391<+:23;?/=   88/B/= . .

(113) %&%&') )!*  '%'(#))$#(")&*('#)( ).%(""$'  

(114) )!*  )!*. '%)*!) ( %)$!$( #!*(( #( !( *- '#( )$'( . !*$.()'$%(  . %&%'$% *'  $"%$(#)(#)$"&*("*'(*(.()" #'+*-#)'!  . *'  $"%'($#![#)$"''!![$"")!($*'(  *'

(115)  $*%)'#(+'(! "$!!%#' *'  '%'(#))$#(")&*('#)( #'('##(   *'  ()'*)*'[*##*'$#   *'  !()$'(#*'$#((!$#(')'($#)$##!() "$'%$!$&*(  *'  '(*"($#)$#( -$#!(   *'  !!*()')$#('#)().%(!!*!(!!( 

(116) *'  !('#)())( [)+)$#! "'$! 

(117) *'  (")()$#! (.#%()'%')) 

(118)  *'.  '%'(#))$#(")&*!!#$!$#'$.)'

(119)  *'  (")()$#. ( "*!)%!( "#("( #!*#L#) ! '#)$# ) !. +!$%%"#)($!$#'$.)( $!( +'(()(+!$%%"#)*-  . *'

(120)  !()'$('#()$'('(#'+*((  *'  /$#(  %'$)$# ( '#)( )$'(  '( #$%)+( * #+*  ! $'#$'(!! "$!!%#'  . *'  ()'*)$#('(%'%'&*(#(!(#'(*)#( #$#)$#*")') !+)(($#*)$# . *'  #*-$#&*( -%'"(#(!(#*'$#((#($'!( %$)#)!!"#)"%!&*(#( !("#("(#$%)$#  . *'  +$(($"()(&*( (##)(   *'  ("'+(! J )$' *%$')!!$# K   *'  $*!')'$)$# #)+(%#$*!$(%#!($*()##)*#(.()"#!(&* #$#"(#*%'(()"*!)$#(#$%)+( . *'  #)'$##-$#((()'*)*'(!"&*( $#())*#)!'*) %%/   *'  #)$"*(.()"""$'%%$"%&*/!%'") )!'$#*'   *'  %'#%!$##-$#( ![".!   *'

(121)  #)$"(#!$#(!(  . .

(122) *'  %%'#)((%'()') J %! K +( J '%$#( K  *'  #)'$##-$#(#)'!$')-'$#)!)!!$)"%$'!   *'  '%'(#))$# (")&* ( ()'*)*'(. "%!&*( #( !( '#)( ).%( . ""$' . *'  "#("!!*!' !%$)#)!()$#!$#)'"   *'  %'#%!(()'*)*'(''!("%!&*(#(!('*)(![#-)  *'  !( '*)(  ![#-) #)'$##-$# #)'. !( '#)( ()'*)*'( ''!(. "%!&*( #( ! )')"#)  ![#$'")$# ( ()"*! -)'*'( )  ! '%$#( %%'$%' . *'

(123)  (")()$#  ![#'$*!"#) ( %'$!$#"#)( $!$#'$.)'( *)$*'  ![-$#%$*'$'"'! # $"%)".!#.  . *'

(124)  ('%)$#('#)(()'*)*'( !".!#   *'

(125)  ()'*)*'!# ".!#   *'

(126)

(127)  $"%$()$#"$!*!'($"#(()*(*#+**#W*  '#+'  . *'

(128)  $##'!)+( %'$)#(!".!#   *'

(129)  ()'*)*'*#  $###)!* ($$'"( %!% ) " . *'

(130)  ()'*)*'(($$'"( %!% ) "  #(!""'#".!#&* . *'

(131)  !(()$#!#&*(%)$!$(.(".!#(#)(!( .  *'

(132)  %$()$#( (*' %!%. ( "*))$#( %'(#)#) / !( '#)( ($*'( "*)#)(. #)*'!(  . *'  (")()$#! +$'%$#(*- %'$)#("!'%!( +$ *%' 

(133) *'  (")()$#  ! +$  ')$# (($ * ')*!*" #$%!("&* +$ '

(134). *'  +!$%%"#) [*# "$! ($*'( (*'-%'"#) ! # %!% "$!( %!$ . ).  

(135)  *'

(136)  +!$%%"#)[*#"$!($*'( #+!%$*'!# %!% ($*'( %!%#*!! 

(137)  *'  (". * %!# -%'"#)!  ![)* %$*' ![+!*)$#  ![)  !. '(%'$#(*'!( !)')$#($"%$')"#)!((($*'( %!%#*!!  . *'  (. .($#)$##"#)( $!$#'$.)'( %*+#) "#'  ( !)')$#(. $#)+(  . %&%. )%. • • • • • • •• ••••• • • •• • • •• • • • • •• • • • • • • • •• • • ••• • •• • • •• •• •• • • • • •• • • •• • • • • • • • • •• • • •• • • •• • • • • •••••••••••••••••••••••••••••••••• ••••••. .

(138) .

(139)   . .

(140) .

(141) +1/,!2 1&,+. "(&#)(#" (; GSeFCH? ?MN OH? MNLO=NOL? FCJIJLINeCKO? JLI>OCN? J;L F?M =?FFOF?M >? /=BQ;HH >;HM F? MSMNdG? H?LP?OR JeLCJBeLCKO? /*, ?N J;L F?M IFCAI>?H>LI=SN?M +(M >;HM F? MSMNdG? H?LP?OR =?HNL;F /*

(142)  !FF? @ILG? ;ONIOL >?M ;RIH?M  OH? A;CH? =IGJ;=N? J?LG?NN;HN F; =IH>O=NCIHM;FN;NICL??N L;JC>?>?F‚CH@FORH?LP?ORF?FIHA>?F;@C<L?

(143)  ‚;ONL?MLmF?MIHNeNe ;NNLC<OeM[F;GSeFCH? ?FF?J?LG?NNL;CNJ;LM;=IGJIMCNCIH?NMIHILA;HCM;NCIH >?Me=B;HA?M MJe=C@CKO?M ;P?= F‚;RIH?  @;PILCM;HN ;CHMC F? G;CHNC?H >? F‚CHNeALCNe ;RIH;F?

(144)  ,;LGC F?M J;NBIFIAC?M AeHeNCKO?M NIO=B;HN F; MO<MN;H=?. <F;H=B?. /. >O /*  ;JJ?Fe?M. F?O=I>SMNLIJBC?M =?LN;CH?M;@@?=N?HNJFOMJLCGCNCP?G?HNF;=IGJIMCNCIH?NF‚ILA;HCM;NCIH>?F; GSeFCH?

(145) (?MJLINeIFCJIJLINeCH?M,(, =I>e?MJ;LF?AdH? %!%

(146) @IHNJ;LNC?>?MJLINeCH?MMJe=C@CKO?M ?NG;D?OL?M>?F;GSeFCH? JLI>OCN?MJ;LF?M+(M

(147) (?MGON;NCIHM>OAdH? %!%

(148) CH>OCM?HN=B?T F‚BIGG? OH F;LA? MJ?=NL? =FCHCKO?  ;FF;HN >? J;NBIFIAC?M BSJIGSeFCHCM;HN?M MePdL?M  F; G;F;>C? >? ,?FCT;?OM )?LT<;=B?L ,)   [ OHN;<F?;O JFOM GI>eLe F;J;L;JFeAC?MJ;MNCKO? FCe?[F‚4>?NSJ?/,# =;L;=NeLCMe?J;LOH?;NN?CHN?;RIH;F?N;L>CP?JLe>IGCH;HN?

(149)  ?M GI>dF?M ;HCG;OR MJIHN;HeM ?N NL;HMAeHCKO?M IHN J?LGCM =?M >?LHCdL?M ;HHe?M >? GC?OR ;JJLeB?H>?L F?M LmF?M >? %!%

(150)

(151) CHMC  >?M GI>dF?M GOLCHM NL;HMAeHCKO?M JLeM?HN;HN OH? MOL?RJL?MMCIH>OAdH? %:>

(152) MIOLCM,(+ IOOH?CHP;FC>;NCIH>OAdH? %:>

(153) MIOLCM,FJHOFF IHN eNe>eP?FIJJeM;@CH>?GI>eFCM?LF?MJ;NBIFIAC?MBOG;CH?M

(154) @CH >? GC?OR ;JJLeB?H>?L F; JBSMCIJ;NBIFIAC? >? =?M @ILG?M >? F?O=I>SMNLIJBC?M  GIH NL;P;CF >? NBdM? ; JILNe MOL >?M ;H;FSM?M =IGJILN?G?HN;F?M  BCMNIFIACKO?M ?N >? <CIFIAC? GIFe=OF;CL? >?M GI>dF?M ;HCG;OR >? /,#  G;CM eA;F?G?HN F?M GI>dF?M >?M GdL?M BeNeLITSAIN?M NL;HMG?NNLC=?M >?,) ?N/,#

(155) !N;HN>IHHeF‚CHNeLfNAL;H>CMM;HNJIOL>e@CHCL F?LmF?>?F;/ ?NJFOMJ;LNC=OFCdL?G?HN>?F; GSeFCH?  >;HM F?M @IH=NCIHM =IAHCNCP?M ?N =IGJILN?G?HN;F?M  =?M GI>dF?M ;HCG;OR J?OP?HN J?LG?NNL? >? GC?OR =IGJL?H>L? =? LmF? ?N >‚;<IL>?L F‚eF;<IL;NCIH >? HIOP?FF?M MNL;NeAC?M NBeL;J?ONCKO?M

(156) JLdM OH? eNO>? <C<FCIAL;JBCKO? =IH=?LH;HN F? /*  F; GSeFCH?  F? AdH? %!%

(157)  F?M J;NBIFIAC?MCH>OCN?MJ;LF?MGON;NCIHM>;HM=?AdH??NF?MLmF?MJIN?HNC?FM>? ,(, >e>OCNM>?M I<M?LP;NCIHMJBSMCIJ;NBIFIACKO?M F?M >C@@eL?HNMLeMOFN;NM>?MeNO>?MMOLF?MGI>dF?M;HCG;OR M?LIHN>eN;CFFeM?N>CM=ONeM MIOM@ILG?>‚;LNC=F?M JIOL?MM;S?L>?GC?OR>e@CHCL F?M@IH=NCIHM >? ,(,

(158). .

(159) .

(160)

(161) 

(162)  

(163). .

(164) .

(165)

(166) 

(167)   

(168). "06018*"+"/3"25 "+1/). L() #&$%) . ','(!"&*)+"(&. (?MSMNdG?H?LP?OR?MN@ILGe>?>?ORJ;LNC?M F? AGABO;3 <3@D3CF13<B@/:(# >IHNF?LmF? ?MN >? L?=?PICL  ?HL?ACMNL?L  CHN?LJLeN?L F?M MCAH;OR KOC J;LPC?HH?HN >? F; JeLCJBeLC?  ?N >‚ILA;HCM?LF;LeJIHM?[?HPIS?L ?NF? AGABO;3<3@D3CF>P@7>6P@7?C3(#% =IHMNCNOeJ;LF?M H?L@M=L^HC?HM?NF?MH?L@MMJCH;OR KOCMIHNL;NN;=BeM;O/*

(169) (?LmF?>O/*, ?MN>?=IH>OCL? DOMKO;O /* F?M CH@ILG;NCIHM CMMO?M >?M Le=?JN?OLM JeLCJBeLCKO?M >? F; M?HMC<CFCNe IO >? F; >IOF?OL ?N>?NL;HMG?NNL?F?MIL>L?MGIN?OLMeGCMJ;LF?M=?HNL?MH?LP?OR

(170)  #1!0'.2'-,,2-+'/3# "3 (? /* ?MN F; J;LNC? >O MSMNdG? H?LP?OR MCNOe? >;HM F; <ICN? =L^HC?HH? 3<1P>6/:3 ?N F; =IFIHH? P?LNe<L;F? ;=3::3 P>7<7O@3 " ?N =IGJL?H> eA;F?G?HN F?M H?L@M =L^HC?HM % H?L@ IF@;=NC@ ?N%% H?L@IJNCKO?

(171) %FM?=IGJIM?>?NCMMOH?LP?OR AFC;F?NP;M=OF;CL? ?N?MN?HNIOLe J;L OH?HM?G<F?>? G?G<L;H?M ;JJ?Fe?M ;P<7<53A

(172). 64B?2 <:=<@.;A@.;.A<:6>B2@:.72B?@1B@F@AS:2;2?C2BE02;A?.9 (? MSMNdG? H?LP?OR =?HNL;F M? >CPCM? ?H NLICM AL;H>M >IG;CH?M  F? NeF?H=eJB;F?  F? NLIH= =eLe<L;F ?N F; GI?FF? eJCHCdL?

(173) ‚;JLdM !FM?PC?L(N>

(174) ILIHIOFJ;?J )?>C=;F,BSMCIFIAS 1J>;N?>!>CNCIH

(175). .

(176)

(177) 

(178)   

(179). . "06018*"+"/3"25 "+1/). V2;0T=5.92. (‚?H=eJB;F?MCNOe>;HMF; <IjN?=L^HC?HH??MN=IHMNCNOe>?eFeG?HNM 64B?2   . !3 13@D3/C IO JLIM?H=eJB;F? KOC ?MN =IHMNCNOe J;L >?OR BeGCMJBdL?M >LICN ?N. A;O=B? MeJ;LeMJ;LF?MCFFIHCHN?L BeGCMJBeLCKO? ?NLeOHCMJ;L>?MMNLO=NOL?M;MMOL;HNOH? =IHH?RCIH ?HNL?=?M>?ORBeGCMJBdL?MF?=ILJM=;FF?OR?NF?M=IGGCMMOL?M

(180) %F =IGJL?H> >?OR JLCH=CJ;F?M MNLO=NOL?M F? BP:3<1P>6/:3 ?NF? 273<1P>6/:3  =?>?LHC?L M?=IGJIM?  >O B6/:/;CA ALIMHIS;OALCMKOCDIO?OHLmF?>?Le=?JNCIH?N>;H;FSM?>?MCH@ILG;NCIHM;P;HN >?F?MNL;HMG?NNL?[F;JeLCJBeLC?>O=?LP?;O=ILN?R=eLe<L;F >?F‚6G>=B6/:/;CA KOCDIO? OHLmF?>?Me=LeNCIH>?MBILGIH?M?N>?LeAOF;NCIH>OMSMNdG?H?LP?ORPeAeN;NC@?NKOC ?MN L?FCe [ FBSJIJBSM? J;L OH? NCA? JCNOCN;CL? ?N >? F‚6G>=>6GA3  OH? AF;H>? KOC LeAOF? F?M ;ONL?MAF;H>?M>?F‚ILA;HCMG?

(181) B?T F‚$IGG?  F; MOL@;=? >O =?LP?;O JLeM?HN? >?M MCFFIHM JFOM IO GICHM JLI@IH>M >IHN =?LN;CHMJILN?HNF?HIG>? A17AAC@3A F?MM=CMMOL?M>?/SFPCOM?N>?.IF;H>IMIHNF?M>?OR JLCH=CJ;F?M ?N J?LG?NN?HN >? >CPCM?L F? =?LP?;O ?H KO;NL? AL;H>M FI<?M  F? :=03 4@=<B/: [ F‚;P;HN F? :=03>/@7PB/: ?NF? :=03B3;>=@/: ;O=?HNL? ?N?H@CHF? :=03=117>7B/: [F‚;LLCdL?

(182) B;KO?FI<??MNNL;P?LMeJ;LNLICMIOKO;NL?MCFFIHMKOCPIHN >eFCGCN?L>?M=CL=IHPIFONCIHM

(183) %F ?MN [ HIN?L KO?  =B?T F; MIOLCM F?M MNLO=NOL?M =eLe<L;F?M MIHN GICHM <C?H >eFCGCNe?M ?H FI<?M G;CM L?MN?HN <C?H =IHM?LPe?M GfG? MC ?FF?M ;JJ;L;CMM?HN >;HM >?M JLIJILNCIHM >C@@eL?HN?M J;L?R?GJF?F;MIOLCMJIMMd>?OH<OF<?IF@;=NC@NLdM>eP?FIJJe?H=IGJ;L;CMIH >?=?FOC>?F‚$IGG? 64B?2 

(184) . !3B@=<11P@P0@/: ?MNF; MNLO=NOL?=?HNL;F?>?F?H=eJB;F?MCNOe?;OHCP?;O>?F;@IMM?. JIMNeLC?OL? ?HNL? F? =?LP?;O ?N F; )!

(185)  /IH ;L=BCN?=NOL? L?JIM? MOL  HCP?;OR  >? B;ON ?H <;M F? ;PA3<1P>6/:3 F? >=<B IO >@=BC0P@/<13 ?NF? 0C:03@/167273<

(186) (?NLIH==eLe<L;F?MN >;<IL>F;PIC?>?J;MM;A?>?MAL;H>?MPIC?M;M=?H>;HN?MPIC?MM?HMCNCP?M?N=eLe<?FF?OM?M ?N>?M=?H>;HN?MPIC?M GINLC=?M PeBC=OF;HN F?M CH@ILG;NCIHM ?NNL;HMG?NN;HNF?MG?MM;A?M JLIP?H;HN>O=ILN?R

(187) %F; eA;F?G?HN OH?CGJFC=;NCIH >;HMF?=IHNLmF?>?F‚;=NCPCNe=;L>C;KO? ?NJOFGIH;CL? G;CM;OMMC>;HMF;LeAOF;NCIH>?MGe=;HCMG?M>‚eP?CF?N>?MIGG?CF

(188) . !313@D3:3B =B?TF‚$IGG? MCNOeMIOMF? =?LP?;O ?N?H;LLCdL?>O NLIH==eLe<L;F ?N>O. =L^H?KOC?MNL?=IOP?LNJ;LF;J;LNC?>?F;<IjN?=L^HC?HH?;JJ?Fe?F=117>CB ?NJ;LF;N?HN?>O =?LP?F?N KOCMeJ;L?F?=?LP?F?N >?MBeGCMJBdL?M=eLe<L;ORMCNOeMCGGe>C;N?G?HN;O >?MMOM >?FOC

(189) %F?MN L?FCe;ONLIH==eLe<L;FJ;L NLICMJ;CL?M>?Je>IH=OF?M=eLe<?FF?OR MOJeLC?OLM. GIS?HM  ?N CH@eLC?OLM

(190)  ,;L =?M Je>IH=OF?M  PIHN J;MM?L NION?M F?M ?@@eL?H=?M ?N ;@@eL?H=?M JLIP?H;HN>?F;GI?FF? >ONLIH==eLe<L;F >?MPIC?MP?MNC<OF;CL?M?N>?MHIS;OR>?MH?L@M. .

(191)

(192) 

(193)   

(194). "06018*"+"/3"25 "+1/). =L^HC?HM

(195) (? LmF? >O =?LP?F?N JILN? MOL F; LeAOF;NCIH >O NIHOM ?N F; =IIL>CH;NCIH >?M GIOP?G?HNM

(196) (‚?H=eJB;F? =IHNC?HNNIOM F?M=?HNL?M>?=IGG;H>? ?N =IIL>CH;NCIH >? F; GINLC=CNe

(197)  %F ?MN F? =?HNL?Le=?JN?OL>?NION?MF?MCH@ILG;NCIHM M?HMILC?FF?M

(198) /;P;M=OF;LCM;NCIH?MN;MMOLe?J;LF?M NLIH=M ;LNeLC?FM =?LPC=;OR ;LNdL?M =;LINC>?M ?N ;LNdL?M P?LNe<L;F?M  ?N F?M NLIH=M P?CH?OR =?LPC=;ORP?CH?MDOAOF;CL?M JF?ROMP?CH?OR=?LPC=;ORJLI@IH>M

(199) . .:<2992 T=6;6S?2. (; )! M?MCNO?>;HMF?JLIFIHA?G?HN>ONLIH==eLe<L;F?N>O <OF<?L;=BC>C?H

(200) !FF?=IGG?H=? CGGe>C;N?G?HN?H>?MMIOM>ONLIOI==CJCN;F

(201) !FF?M‚CHNdAL??HNIN;FCNe >;HMF? =;H;FL;=BC>C?H G;CM M?N?LGCH? =B?TF‚$IGG? ;OHCP?;O>?F;JL?GCdL?P?LNd<L?FIG<;CL?(

(202) J;LNCL>? F;GI?FF??N>? =B;KO??MJ;=?CHN?LP?LNe<L;FMILN?HNF?MH?L@MMJCH;OR=IHMNCNOeM>OH?L;=CH? ;HNeLC?OL? GINLC=?  ?N >OH? L;=CH? JIMNeLC?OL? M?HMCNCP? 64B?2

(203) 

(204) !H >?MMIOM >? ( ?N DOMKO;OM;=LOG F? =;H;FL;=BC>C?H?MNI==OJeJ;LF?ML;=CH?M>?MH?L@MMJCH;ORCMMO?M>?F; GI?FF?FIG<;CL?F?HM?G<F?>?=?ML;=CH?M KOCM?GeF;HA?HN?NM?=IH@IH>?HN @ILG?=?KO? FIH;JJ?FF?=IGGOHeG?HNF;KO?O? >? =B?P;F

(205) /OL NION? M; FIHAO?OL  F; GI?FF? ; OH? MNLO=NOL? BIGIAdH?

(206)  !FF? ?MN @ILGe? >OH ;R? >? AC0AB/<135@7A3 /# KOC;F;@ILG?>OH?;CF?>?J;JCFFIH?HNIOLe>? AC0AB/<130:/<163 /

(207) (; /# ?MN@ILGe? J;LF?M=ILJM=?FFOF;CL?M>?MH?OLIH?M ?NF; / J;LF?J;MM;A?>?MAL;H>?M PIC?M GINLC=?M  M?HMCNCP?M  =eLe<?FF?OM?M  ?N ?RNL;JSL;GC>;F?M

(208)  (; PIC? GINLC=? IO PIC? JSL;GC>;F? ?MN =IHMNCNOe? >OH @;CM=?;O >?M=?H>;HN >CL?=N ?N OH @;CM=?;O =LICMe CF PC?HN >O =?LP?;O>O=mNeIJJIMe

(209) %F?RCMN?>?ORPIC?MM?HMCNCP?M  C<3D=73/A13<2/<B327@31B3 23:/ A3<A707:7BP >@=>@7=13>B7D3 >@=4=<23 M?HM >?M JIMCNCIHM  M?HMC<CFCNe PC<L;NICL? ?N >? F; M?HMC<CFCNe MOJ?L@C=C?FF? N;=NCF? eJC=LCNCKO? M?HM >O NIO=B?L ?N KOC ?MN MCNOe? ;O HCP?;O >?M =IL>IHM JIMNeLC?OLM >? F; GI?FF?   C<3 D=73 /A13<2/<B3 23 :/ A3<A707:7BP 2=C:=C@3CA3 3B B63@;7?C3 KOC NL;P?LM? F? =?HNL? >? F; GI?FF? ;P;HN >? J;L=IOLCL F?M @;CM=?;OR ;M=?H>;HNM F;NeL;OR>?F;GI?FF?

(210). .

(211)

(212) 

(213)   

(214). "06018*"+"/3"25 "+1/). 64B?2 <:=.?.6@<;129V.;.A<:620T?T/?.92129V<::22A129.@<B?6@ ;HM F? =?LP?;O BOG;CH  GfG? M‚CFM =IIJdL?HN NIOM ?HM?G<F?  IH J?ON ;NNLC<O?L [ =B;KO? FI<? OH? @IH=NCIH CGJILN;HN? =IGG? F?M GIOP?G?HNM PIFIHN;CL?M  F; GINLC=CNe  F; GeGICL? IO F; @IH=NCIH PCMO?FF?

(215)  (? =?LP?;O GOLCH?MNKO;HN[FOC>eJIOLPO>?FI<?MG;CMF?MMNLO=NOL?M=eLe<L;F?MMIHN<C?H=IHM?LPe?M?HNL?F‚$IGG??NF; MIOLCM

(216)  ;JLdM LS;H;H>$IFG?M . 64B?2

(217)  <B=2A?.;@C2?@.9212:<2992T=6;6S?2 (;GI?FF?eJCHCdL?M?=IGJIM?>?>?ORMNLO=NOL?M F;MO<MN;H=?<F;H=B?@ILGe?J;LF?J;MM;A?>?MAL;H>?MPIC?M GINLC=?M M?HMCNCP?M =eLe<?FF?OM?M ?N?RNL; JSL;GC>;F?M ?NF;MO<MN;H=?ALCM?@ILGe?J;LF?M=ILJM=?FFOF;CL?M>? H?OLIH?M

(218) ‚;JLdM </B=;733B>6GA7=:=5736C;/7<3A

(219) !F;CH?*

(220) );LC?< ,?;LMIH!>O=;NCIH

(221). .

(222)

(223) 

(224)   

(225).

(226) . "06018*"+"/3"25 "+1/). 2@;2?3@0?O;62;@. ($IGG? JIMMd>?  J;CL?M >? <3@4A >P@7>6P@7?C3A >IHN F?M >?OR JL?GC?LM JL?HH?HN F?OL ILCACH?>;HMF?=?LP?;O?NF?M;ONL?M>;HMF?NLIH==eLe<L;F 64B?2 

(227) +HF?M;JJ?FF? ;OMMC F?M <3@4A 1@M<73<A =;L CFM eG?LA?HN >CL?=N?G?HN >? F‚?H=eJB;F? =IHNL;CL?G?HN [ NIOM F?M ;ONL?M H?L@MKOCeG?LA?HN>?F;)!

(228) ?MH?L@MMIHN=F;MMeM>? %[ 4%%  0LICMMIHN >? BG>3A3<A=@73: F?M H?L@M IF@;=NC@ 7%8  IJNCKO? 7%%8 ?N ;O>CNC@ 72%%%8 ;JJ?Fe ;OMMC P?MNC<OFI =I=BFe;CL?  =CHK MIHN >? BG>3;=B3C@F?MH?L@MI=OFIGIN?OL 7%%%8 NLI=BFe;CL? 7%28 GIN?OLI=OF;CL??RN?LH?IO ;<>O=?HM 72%8  MJCH;F 74%8 ?N AL;H> BSJIAFIMM? 74%%8 ?N KO;NL? IHN [ F; @ICM OH? @IH=NCIH M?HMILC?FF? ?N GINLC=?  ?N MIHN >CNM ;7FB3AF?M H?L@M NLCDOG?;O 728  @;=C;F 72%%8  AFIMMI JB;LSHAC?H 7%48 ?N JH?OGIA;MNLCKO? 748 ;JJ?Fe eA;F?G?HN H?L@ P;AO?

(229) (? LmF? >?M H?L@M =L^HC?HM?MN>‚;MMOL?LHIM=CHKM?HM F?MGIOP?G?HNM>OPCM;A? F;>eAFONCNCIH ?NF;JBIH;NCIH

(230). 64B?2 &2=?T@2;A.A6<;@05T:.A6>B212@1633T?2;A@;2?3@0?O;62;@. .

(231)

(232) 

(233)   

(234). "06018*"+"/3"25 "+1/).  -+.02'+#,22'-, "3 . . .@B/@A.;024?6@22A92@;2B?<;2@. (; /# =IHNC?HN ?MM?HNC?FF?G?HN F?M =ILJM =?FFOF;CL?M >?M H?OLIH?M  F?M JLIFIHA?G?HNM >?H>LCNCKO?M >?M H?OLIH?M ?N F?M =IHH?RCIHM CHN?L H?OLIH;F?M IO MSH;JM?M 64B?2 

(235)  (?M H?OLIH?M. =?FFOF?M B;ON?G?HN MJe=C;FCMe?M ?N ?R=CN;<F?M  J;LNC=CJ?HN [. F‚e=B;HA?. >‚CH@ILG;NCIHM

(236) ?NN?CH@ILG;NCIH?MNNL;HMGCM?[NL;P?LMF?H?OLIH?MIOMF;@ILG?>‚OHCH@FOR H?LP?OR=IHMNCNOeJ;LOH?MO==?MMCIH>? JIN?HNC?FM>?G?G<L;H?>eJIF;LCM;HNM IO >=B3<B73:A 2\/1B7=< , ?N ;O HCP?;O >?M MSH;JM?M J;L F; FC<eL;NCIH >;HM F; @?HN? MSH;JNCKO? >? H?OLINL;HMG?NN?OLM MJe=C@CKO?M >O NSJ? H?OLIH;F

(237)  (‚CH@FOR H?LP?OR ?MN NL;HMGCM >? @;bIH =?HNLCJdN?>?JOCMF;MSH;JM?J;LF?M>?H>LCN?MDOMKO‚;OR=ILJM=?FFOF;CL?MH?OLIH;ORKOCPIHN ?HA?H>L?L  ?H LeJIHM? [ =?N CH@FOR  OH? HIOP?FF? CH@ILG;NCIH MIOM @ILG? >‚OH JIN?HNC?F >? G?G<L;H?

(238)  (? H?OLIH? =IHNC?HN  JIOL MIH <IH @IH=NCIHH?G?HN  OH =SNIJF;MG? LC=B? ?H ILA;H?FF?M?N?HGIFe=OF?M>CP?LM?M>IHNF;LeJ;LNCNCIH?MNMJe=C@CKO??NHIHBIGIAdH?

(239) B;KO? H?OLIH? ?MN OHCKO? >? J;L M; @ILG? J;LNC=OFCdL?  F; JIMCNCIH KOCF I==OJ? >;HM F? MSMNdG?H?LP?OR?NF?M=IHH?RCIHMKOCF?HNL?NC?HN;P?=>;ONL?MH?OLIH?MIO;P?=>?M=?FFOF?M Le=?JNLC=?MM?HMILC?FF?MIO?@@?=NLC=?MGOM=OF;CL?MIOAF;H>OF;CL?M

(240) (?M =ILJM =?FFOF;CL?M J?OP?HN GIHNL?L OH? AL;H>? P;LC;<CFCNe >? @ILG? eNICFeM  @OMC@ILG?. =IHCKO?  JIFSe>LCKO?  MJBeLCKO?  JSL;GC>;F? ?N >? N;CFF?

(241) (; AeIGeNLC? >?M >?H>LCN?M ?N >? F;RIH? P;LC? ;OMMC eHILGeG?HN M?FIH F? LmF? >O H?OLIH? >;HM F? =CL=OCN H?LP?OR

(242) /?FIH >?M =LCNdL?M @IH=NCIHH?FM ?N GILJBIFIACKO?M  IH J?ON =F;MM?L F?M H?OLIH?M MIOM >C@@eL?HN?M =;NeAILC?M 64B?2 . 23A7<B3@<3C@=<3A IOH?OLIH?<CJIF;CL?MKOC=IHH?=N?HN?HNL??OR>C@@eL?HNMH?OLIH?M. [FCHNeLC?OL>O =?LP?;O IO>?F;)!

(243)  %FMIHN>?ORJLIFIHA?G?HNMJLCH=CJ;OR>?FIHAO?OL MCGCF;CL?

(244) . 23A <3C@=<3A A3<A=@73:A IO OHCJIF;CL?M KOC =;JN?HN F?M G?MM;A?M >?M Le=?JN?OLM. M?HMILC?FM?NF?M=IGGOHCKO?HN;OMSMNdG?H?LP?OR=?HNL;F

(245) %FMIHNOH=IOLNJLIFIHA?G?HN KOCM?MO<>CPCM?L;JC>?G?HN?H>?OR FOH@;CM;HNI@@C=?>?>?H>LCN? F;ONL?>;RIH?

(246) . 23A <3C@=<3A ;=B3C@A IO GOFNCJIF;CL?M KOC =IH>OCM?HN F; =IGG;H>? GINLC=? >O. =ILN?R[F; )! IO>?F;GI?FF?;ORGOM=F?M

(247) %FMIHN>? =IOLN?M >?H>LCN?MeG;H;HN>O=ILJM =?FFOF;CL??NOHFIHA;RIH?

(248) ‚;ONL?MNSJ?M=?FFOF;CL?M F?M=?FFOF?M AFC;F?M MIHNeA;F?G?HNJLeM?HN?M>;HMF;/# ;CHMCKO? >?HIG<L?OR=;JCFF;CL?MM;HAOCHM

(249). .

(250)

(251) 

(252)   

(253). "06018*"+"/3"25 "+1/). 64B?2'A?B0AB?21VB;;2B?<;2 (? H?OLIH? ?MN =IHMNCNOe >‚OH =ILJM =?FFOF;CL? KOC =IHNC?HN F? HIS;O ?N F? =SNIJF;MG?  ?N >? >?OR NSJ?M >? JLIFIHA?G?HNM  F‚;RIH? ?HNIOLe>‚OH?A;CH?>?GSeFCH??N=IH>OCM;HNF?MJIN?HNC?FM>‚;=NCIH>?@;bIHM;FN;NICL? >?HvO>?HHvO>DOMKO‚[F;N?LGCH;CMIHIp>?MH?OLINL;HMG?NN?OLMMIHNFC<eLeMP?LMF;@?HN?MSH;JNCKO? ?NF?M >?H>LCN?M JLIFIHA?G?HNM;@@eL?HNM =IH>OCM;HN F‚CH@FORH?LP?ORCH>OCN[F?OL?RNLeGCNeDOMKO‚;O=ILJM=?FFOF;CL?

(254). 64B?2 2@0.AT4<?62@12;2B?<;2@@29<;12@0?6AS?2@3<;0A6<;;29@2A:<?=5<9<46>B2@ (?M H?OLIH?M <CJIF;CL?M eN;<FCMM?HN F?M =IHH?RCIHM ?HNL?M H?OLIH?M  F?M H?OLIH?M OHCJIF;CL?M NL;HMG?NN?HN F?M G?MM;A?MM?HMILC?FM?NF?MH?OLIH?MGOFNCJIF;CL?M =IH>OCM?HNF;=IGG;H>?GINLC=?

(255). .

(256)

(257) 

(258)   

(259). . "06018*"+"/3"25 "+1/). .@B/@A.;02/9.;052. (;/ ?MNOH=IGJ;LNCG?HN>?=IH>O=NCIHKOC=IHNC?HN?MM?HNC?FF?G?HN>?M;RIH?MGSeFCHCMeM. =ILL?MJIH>;HN ;OR JLIFIHA?G?HNM H?OLIH;OR ?N >?M =?FFOF?M AFC;F?M  J;LGC F?MKO?FF?M IH >CMNCHAO?F?M P>3<2G;=1GB3A F?M 13::C:3A;71@=5:7/:3A F?M /AB@=1GB3A ?NF?M =:75=23<2@=1GB3A +(M

(260) .. 2@.E<;2@. ,IOLL?PO? ?<;HH??N;F

(261)  (?M /F=<3A MIHN>?MJLIFIHA?G?HNM=SNIJF;MGCKO?MH?OLIH;OR=IH>OCM;HNF‚CH@FORH?LP?OR>? @;bIH =?HNLC@OA? >O =ILJM =?FFOF;CL? H?OLIH;F DOMKO‚;OR N?LGCH;CMIHM H?LP?OM?M

(262)  ?OR NSJ?M >CMNCH=NM>‚;RIH?MM?MCNO?HN>;HMF?M/*?N/*,>?M;RIH?MGSeFCHCMeM?NHIHGSeFCHCMeM

(263) (?M /F=<3A ;GP:7<7APA MIHN L?=IOP?LNM >‚OH? A;CH? >? GSeFCH? JLIP?H;HN >?M =?FFOF?M >? /=BQ;HH >;HM F? /*, ?N >?M +(M >;HM F? /*

(264)  %FM M? =IGJIM?HN ?H  =IGJ;LNCG?HNM  OH M?AG?HNCHCNC;F>‚Ip M?>e=F?H=B?HN F?M, OH;RIH?GSeFCHCMe>?N;CFF?P;LC;<F?KOCNL;HMG?N F‚CH@ILG;NCIH  ?N OH M?AG?HN @CH;F ;O >?F[ >OKO?F F?M N?LGCH;CMIHM MSH;JNCKO?M M‚eN?H>?HN 64B?2

(265) (;GILJBIFIAC?>?M;RIH?M ?HN?LG?M>?FIHAO?OL?N>C;GdNL? ?NF; =IGJF?RCNe >? F‚;L<ILCM;NCIH ;RIH;F? MIHN J;LNC=OFCdL?G?HN P;LC;<F?M

(266)  (‚;ONL? =;L;=NeLCMNCKO? GILJBIFIACKO? >?M ;RIH?M ?MN F; JLeM?H=? >? HIG<L?OR <IONIHM MSH;JNCKO?M KOC MIHN >CMNLC<OeMF?FIHA>?M<L;H=B?M@CH?M>?M;RIH?M

(267) #eHeL;F?G?HN F?M ;RIH?M >O /* MIHN B;ON?G?HN L;GC@CeM ?N =IHN;=N?HN >? HIG<L?OR H?OLIH?M=C<F?M>?@;bIHFI=;F?IO>CMN;HN?

(268) );CMF;@IH=NCIH>?F‚;RIH?H‚?MNJ;MJOL?G?HN FCGCNe?[F;=IH>O=NCIH>?M, >OMCN?>‚CHCNC;NCIHJLdM>O=ILJM=?FFOF;CL?;ORN?LGCH;CMIHM

(269) ?MNL;P;ORLe=?HNMIHNGIHNLeMKO?>?M IJeL;NCIHM=IGJF?R?MMIHNMJe=C@CKO?G?HN ?Re=ONe?M F?FIHA>?F‚;RIH??NKO‚CF?MN=;J;<F?>?=IHNLmF?LF;NL;HMGCMMCIH>?MMCAH;OReF?=NLCKO?M ?H J;LNC=OFC?L>?>eN?LGCH?LF‚?@@C=;=CNe?NF?>eF;C>?F;NL;HMGCMMCIHMSH;JNCKO?

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