++++++++++++++<%#-&=(/,.+>/*()$,%)+ m+
@"#3%+.#-.+3%..%+3)(,..#-$%+@),.%+@#)+"%+-/*0),C/%+D#-.+"%+*(-D%+D\#/H(/)D\4/,+%$+"#+-03%..,$0+D%+'()*%)+
D%.+,-D,B,D/.+#D#@$0.+N+3%+*(-D%+s+0$#-$+D(--0F+D\#/$)%+@#)$F+"%.+#B#-$#J%.+#B0)0.+D%+3%)$#,-.+(/$,".+.@03,&
',C/%*%-$+3(-K/.+N+D%.+',-.+D\%-.%,J-%*%-$+%$8(/+D\#@@)%-$,..#J%+3(**%+"%+$(/$+)03%-$+$#Y"%#/+-/*0&
),C/%+(/+"%+D0HN+Y,%-+B,%,"+%O%)3,.%/)+@%)*%$$#-$+"\%-$)#,-%*%-$+,-D,B,D/%"+N+"#+)0#",.#$,(-+D%+$x34%.+.,*@"%.+
%$+#../)#-$+"#+3())%3$,(-+#/$(*#$,C/%+R,**0D,#$%F+.#-.+),.C/%+D%+D0)#@#J%+#''%3$,'S+D%.+@%)'()*#-3%.2+
;lS+>#-.+"%.+L(-%.+#B#-30%.+D%+"#+')#-3(@4(-,%F+"\0C/,@%*%-$+%-+*#$0),%"+,-'()*#$,C/%+D%.+0$#Y",..%*%-$.+
.3("#,)%.+%.$+J0-0)#"%*%-$+*(,-D)%F+$#-$+%-+C/#-$,$0+C/\%-+-(/B%#/$0F+C/%+3%"/,+D%.+'#*,""%.F+%O3%@$0+
3%""%.+D%+"#+lower!lower!class!%$+R@%/$&^$)%S+3%""%.+C/,+'()*%-$+"\0",$%+$)#D,$,(-#",.$%F+"#+.@4A)%+3/"$/)%""%+D,$%+
W+/-,B%).+D%.+3"#..,C/%.+X+R>(--#$F+:ZZ[S+C/,+.%+3(*@(.%+*#H(),$#,)%*%-$+D%+C/,-C/#J0-#,)%.+Y,%-+D,@"f&
*0.+#_#-$+J#)D0+"%/).+D,.$#-3%.+%-B%).+"%.+'()*%.+#)$,.$,C/%.+"%.+@"/.+)03%-$%.+%$+-\%O@"(,$#-$+J/A)%+"%.+
)%..(/)3%.+D%+"#+$%34-("(J,%+#/D,(B,./%""%2+Q%+-\%.$+D(-3+@#.+N+"\03("%+C/%+"#+*#H(),$0+D%.+H%/-%.+#@@)%-&
-%-$+N+.%+.%)B,)+D%.+@)(D/,$.+D%+"\,-J0-,%),%+-/*0),C/%+%$F+"#+@"/@#)$+D/+$%*@.F+3%/O+D(-$+,".+.%+.%)B%-$+D#-.+
"\%.@#3%+.3("#,)%+#,-.,+C/%+"%.+3(-D,$,(-.+D#-.+"%.C/%""%.+,".+.\%-+.%)B%-$+e+"\/.#J%+3(""%3$,'+D\/-+*#$0),%"+
(Y.("A$%+$%*@()#,)%*%-$+D,.@(-,Y"%+e+-%+3(-'A)%-$+@#.+#/O+./@@()$.+D%.+#3$,B,$0.+@)(@)%.+N+"#+D,.3,@",-%+
W+')#-K#,.+X+%$+N+3%.+#3$,B,$0.+*^*%.+R.,+%""%.+,*@",C/%-$+"%+)%3(/).+N+"\(/$,"+,-'()*#$,C/%S+/-+J)#-D+@(/B(,)+
D\#$$)#3$,B,$0+%$+/-%+@/,..#-$%+B%)$/+D\,-$0)%..%*%-$2+V-%+B%)$/+%$+/-+@(/B(,)+$%".+C/\,".+'#..%-$+(/Y",%)+"%.+
@(..,Y,",$0.+C/\('')%+"\0C/,@%*%-$+@%).(--%"+D\#..(/B,)+"#+3/),(.,$0F+D%+3(*Y"%)+"%+Y%.(,-+D%+3/"$/)%+@#)$,3,&
@#$,B%+#/+.%,-+D\/-%+3(**/-#/$0+D%+fansF+D%+.#$,.'#,)%+N+$(/$+*(*%-$+"\%-B,%+D%+3(-$#3$.+in!vitro!RQ#..,",F+
79::S,+D%+D(--%)+,../%+#/+D0.,)+D\0B#.,(-+D#-.+"%.+*(-D%.+',3$,(--%".+%$+D\_+3(-3)0$,.%)+D%.+'#-$#.*%.+@#)+
"\,-$%)B%-$,(-+B,)$/%""%2+Q%+C/\(/B)%+"\()D,-#$%/)+@%).(--%"+(/F+N+'()$,(),F+"\,!#DF+$(/H(/).+N+@()$0%+D%+*#,-F+
3\%.$+/-+%.@#3%+,-',-,+D%+",Y%)$0+,-D,B,D/%""%F+/-+%.@#3%+(I+"%+D0@"#3%*%-$+e+"#+B,$%..%+D%+D0@"#3%*%-$+
./)$(/$+e+D(--%+#/O+%-'#-$.+%$+#/O+#D("%.3%-$.+"\,""/.,(-+D%+.\0*#-3,@%)F+/-+%.@#3%+(I+"%.+@(..,Y,",$0.+
D\,-$%)#3$,(-+.#-.+)0%"+D#-J%)+"%/)+D(--%-$+"\,""/.,(-+D/+@(/B(,)2+!#)+3(-$)#.$%+R%$+@%/$&^$)%+%-+'()K#-$+"%+
$)#,$SF+"\0C/,@%*%-$+,-'()*#$,C/%+D%+"\03("%+-%+D(--%+J0-0)#"%*%-$+#33A.+C/\N+/-+D(*#,-%+",*,$0+(I+,"+'#/$+
*#)34%)+#/+@#.+.#-.+.\03#)$%)+D%.+34%*,-.+Y#",.0.2+!%/$&(-F+C/#-D+(-+#+0@)(/B0+$#-$+D%+'(,.+"%+.%-$,*%-$+
D%+@/,..#-3%+C/%+@)(3/)%+"%+34(,O+RD\/-%+#@@",3#$,(-F+D\/-+@)(J)#**%F+D\/-+",%-F+D\/-%+,-$%)B%-$,(-F+%$32SF+
34%*,-%)+D(3,"%*%-$+%-$)%+D\0$)(,$%.+')(-$,A)%.+o+!%/$&(-+-%+@#.+0@)(/B%)+"#+-(.$#"J,%+D%.+B#.$%.+4(),&
L(-.+o+!
mlS+>%@/,.+/-%+C/#)#-$#,-%+D\#--0%.+"#+3(-',J/)#$,(-+D%+"#+D,.3,@",-%+W+')#-K#,.+X+Ri%/$%)+h+=#4#-,%)&i%/$%)F+
799;SF+D#-.+"%.+D,''0)%-$%.+'()*%.+D\%-.%,J-%*%-$+%$+N+$(/.+"%.+.$#D%.+D/+3/)./.+%.$+#''%3$0%+D%+$/)Y/&
"%-3%.2+Q%.+D%)-,A)%.+.(-$+#3$/%""%*%-$+@)(B(C/0%.F+#/+@)%*,%)+34%'F+@#)+"%+D0@4#.#J%+3/"$/)%"+%-$)%+"%+
*(DA"%+.3("#,)%+D/+H%/-%+C/,+%-$#*%+/-+@#)3(/).+@)('%..,(--%"+(/+C/,+@(/)./,$+.%.+0$/D%.+%$+3%/O+*,.+%-+
0B,D%-3%+@#)+"#+.(3,0$0+*#)34#-D%F+B,#+"\,-D/.$),%+%$+"%+3(**%)3%+D\/-%+3/"$/)%+H/B0-,"%+D%+@"/.+%-+@"/.+
/-,',0%+R!#.C/,%)F+799mSF+(/+B,#+"\,-D/.$),%+%$+"%+3(**%)3%+D\/-%+3/"$/)%+)0.%)B0%+N+/-%+0",$%+.0"%3$,(--0%+
@#)+"\#)J%-$2+=%+@),-3,@#"+@(,-$+3(**/-+D%+3%.+*(DA"%.+%.$+/-+,-D,B,D/#",.*%+40D(-,.$%+$%*@0)0+@#)+/-%+
.(3,#Y,",$0+./@%)',3,%""%+(/8%$+",*,$0%+N+/-%+3(**/-#/$0+D%+@#,).2+Q%"#+%.$+'()$+@%/+3(*@#$,Y"%+#B%3+"\,D0#"+
W+4/*#-,.$%+X+@)0.,D#-$+R('',3,%""%*%-$+$(/$+#/+*(,-.S+N+"#+.3("#),.#$,(-2+!(/)+3%+C/,+-(/.+3(-3%)-%F+3%$+
,D0#"+4/*#-,.$%+@(/))#,$+.%+3(-3)0$,.%)+D#-.+/-+Y/$+D,.3,@",-#,)%+3(**%+"\#3C/,.,$,(-+D%+3(*@0$%-3%.+D%+
3(**/-,3#$,(-+R%..%-$,%""%*%-$S+B%)Y#"%+C/,+.$)/3$/)%-$+"#+@%-.0%F+#33)(,..%-$+"\%.$,*%+D%+.(,+%$+"%+)%.@%3$+
D\#/$)/,F+J#)#-$,..%-$+"\0*#-3,@#$,(-+,-$%""%3$/%""%F+D0B%"(@@%-$+"\%.@),$+3),$,C/%F+'#B(),.%-$+"#+*(Y,",$0+.(&
3,#"%+%$+)%-D%-$+@(..,Y"%+D%.+034#-J%.+D0B%"(@@#-$+"%+@($%-$,%"+D\4/*#-,$0+D%+34#3/-+e+-($#**%-$+
@#)3%+C/\,".+@()$%-$+./)+D%.+./H%$.+*%$$#-$+3%+@($%-$,%"+%-+C/%.$,(-+a+H\0B(C/%+#,-.,F+%-+@#..#-$F+"%+)f"%+ir=
remplaçable+-(-+D%+"#+",$$0)#$/)%F+*#,.+D\/-%+3%)$#,-%+#@@)(34%+D\/-%+3%)$#,-%+",$$0)#$/)%+Rr(D()(BF+799bS2+
>%@/,.+"#+*#..,',3#$,(-+D%+"\%-.%,J-%*%-$F+#/+3(/).+D%.+#--0%.+:Zb9F+"#+3(-',J/)#$,(-+D%+-($)%+D,.3,@",-%+
-\#+3%..0+D\^$)%+*(D,',0%+@#)+$(/$%.+.()$%.+D%+$%-$#$,B%.+D\#D#@$#$,(-+D%.+3(-$%-/.+#/O+#@$,$/D%.+%$+#/O+
D,.@(.,$,(-.+D\/-%+@(@/"#$,(-+.3("#,)%+D\#Y()D+@"/.+3/"$/)%""%*%-$+Y,J#))0%+C/\%""%+-%+"\#B#,$+H#*#,.+0$0F+
%-./,$%+@)(J)%..,B%*%-$+/-,',0%+@#)+D%.+J(/$.F+D%.+B#"%/).F+D%.+@)#$,C/%.+3)%/.#-$+"%+'(..0+D%.+J0-0)#$,(-.+
%$+)%-D#-$+@"/.+D,'',3,"%+C/%+-#J/A)%+"%+@#..#J%+D/+)%"#,+3/"$/)%"2+c-+-%+.#/)#,$+#'',)*%)+C/%+3%.+$%-$#$,B%.+
#,%-$+#Y(/$,+N+"#+.$#Y,",.#$,(-+D\/-%+3(-',J/)#$,(-+D(-$+"%+3`/)+%.$+"#+@)(D/3$,(-+%$+"#+3(@)(D/3$,(-+D%.+
D,.3(/).F+%-$%-D/.+3(**%+@)(D/,$.+D\#3$%.+D%+3(**/-,3#$,(-+R@),-3,@#"%*%-$S+B%)Y#"%F+3#)F+H/.$%*%-$F+
/-%+Y(--%+@#)$,%+D\%-$)%+%""%.+#+3(-.,.$0+N+'#,)%+@)%-D)%+%-+34#)J%+@#)+"%.+%-.%,J-#-$.+D%+')#-K#,.+R,-./'',&
.#**%-$+@)0@#)0.+@(/)+3%+'#,)%S+D%.+(YH%$.+.0*,($,C/%.+4_Y),D%.+)%"%B#-$+D%+3%+C/%+"\(-+#@@%""%+#/&
H(/)D\4/,+"#+W+",$$0)#$,%+,3(-($%O$/%""%+XF+"#+W+",$$0)#$,%+*/"$,*(D#"%+X+e+(/+"#+W+",$$0)#$,%+-/*0),C/%+X+.,+