Kdi adh a rliav UIR ehnt took panrsi -;&tg yeeR rendsomy, a ahcipet hcnyhapl.opeate eTehr is eadnercis nioamma oidptorcun esbeuca fo the ierlv eadmag, enadigl to .mmeiemyohanapr ishT estg to het ,rbain is oterdnecv to maengilut a(n mo).lyeost hsTi csause hte irnab leigwsnl.

It's ton )E railv iechleitapsn ueecbas ti ieslmpi eht uivrs is ilycetdr usngcia hte iehc.silaenpt n,etd sIa hte rlvia inoftceni &;t-g npriisa ;&-gt eivlr edamag gt;-& inmaaom -gt;& reosssc BBB ;&-tg doecnevtr ot lemtgiaun gt&;- asdwr in atwre -> lceaebrr medea

noas8e//sdp-s.ealatntt0ah:go0ct/sl7iorptm0tpthebhttnpclyep/s1ec.mi/aihl1eeu

shiT si iamtsectat enrla elcl oicamnacr 20A(F02 6p)05 rof eht lolognwfi nsraso:e

• oythayilPmec - siht si het rrypmai celu, sa ti si siaacestdo with pciotec POE or(iephiot)rtny esconerti in cnspteoaralapi oysresmdn F022A0( )8p22, wchih nac eb cdusae yb om,ocoetphoaryhmc rlaen llce ,canoicarm lrlteuhleocap rao,icmcan asiomalobgmhntae and olmay.meoi fO etshe, noyl rvile dan idknye oudwl eb a choeic vgnie nad taeclhloarpelu riomncaac is ritorccne eabescu he did not ehav nay dsotieasca nndiigf fo dicun,aje eehgtal,pmoay ca,tsise or nraiaeox 2(0F2A0 .9)p23 ulP,s the rilve dsoe not mclonomy aziasstteem ot rinab aeerhsw nyiked dsoe FA0(022 3)2p2
• crmaaeypHcile - tshi is iykell adeiivitcn of PrTPH rsointeec, and lrane ellc icnrmcaao si noe of teh rcnaesc that nca do hits. Hvo,eewr tshi is ifalyr pcnncoiefsi sa reeth rea mnya naercsc taht acn etseecr PPr.HT
• mratieHaua - tuesgsiveg of nyiurak/yidern rctat vnielontvem
• vNetaige for acnbimicrcoerony nnagiet - thsi is a pinccieosfn mreakr ailnym rfo noolc dna cnpaetcria necrcas A2F0(20 p2)26

• nurgBin oalibndmA iaPn rohsu earft aiegtn = satiGrc cruel
• Bclak lotoss orf 2 asdy = ???
• fatRcoeyrr ot TCO andAstci dan 2H sBecolkr
• nwegiSat dna woL BP
• ecaiatcPrn sMas = omst lkeiyl SRGAAIONMT

meImthisoulhnaciocm lglebina suse tinbsoiaed sa skrrmae rfo hawt tyhe natw to di.fn nI shit aec,s we'er gcinspstue itsarng igvne het pysommst

t:eNo Yuo duhslo rsviee het ic,tuofnn is,aomutnlti and tesi fo aeelrse for eahc fo hte onshemro endtmoien sa wlel

:ERN EEERCFr-nosnilgollZElie eyrSdmon

I llce iaedsse ei—dnrhet i yososalml rstgaoe sidrdero oat(mauosl vsr;cee)esi ecetfd ni caih1l-ylucl-o-neshsntatpesraeogoNafyprms >-- erulfia of teh oilGg ot haperlpootshy semonna eedusirs (deaercse a)6po-oesnmh-thnpase no osenlyrgctoip g&t-;- roeintsp  rae srdeceet aarlyxlutelrlec ratreh nhat relidvdee to sooysmlse

(iciNna tiV B3)
- ihitsbin isillposy ( nmoehro ivnseseti aespil ) nda capthie LVDL sshsenyti teoiecn/rs .

ideS ftesfce :cFlaia nhlusgif , orseayncd to nnpsdiaotlrag leereas . Pre taetr tihw ANDSSI
- olAs esusac yaegiypHe;rmlc nad ypicameireruH , sa hucs aoivd in ouytG nttspiea and scbtDeiia

ATCUE aloolhc niiitsbh YCP → eansreIdc baiiaitvbiyoall of tpechinnomeoa

HCCONRI ocalolh eiusncd YPC → udontniIc fo hemocyortc P405 yemznes atht ivettaac oheniatnpamec to a oxthoitcepa aimeetbotl

I tgo tish rnogw sacebeu I dusseam hicnroc hocallo etnma syera nda ye.sra I gseus a eedwnek wlil usfic?ef

s,nyHolte kucf itsh .mpboerl

I thikn stih si yedsngSolotri slsoteicrar ()ramehwodrt is a ormdnworu hwose rlevaa eliv in slio adn who nca eacus poyurnlma dseiase. tI ahs teh tiilaby ot etnrptaee nski form hte lios btu cna olas eb eodtianb by iisggennt eescf nsotciaenatm slio (0A20F2 9p)15hfi:oefgintoyrws/pg/gawmt/...asso_s/taslt/dhevwn/rctldcpnieoqs

tMos sniieltnta uordwmnrso era loaealfrc- outre ceeptx eignoosydsrtl hwhci can aosl npeteater ,nski rohokwom etan(cro ca)arimunes ihchw nlyo ersaenptte ,skni dan anrihielltc whhci anc oecm fmor uecedornodk meast eiaeyl(spcl p)okr tbu oeshw stpommsy od tno catmh htta of the p.neaitt cilhraTnlie aavlre rntee eht ldboo atmers nad tcfine slemuc dna acn aslo eucsa ointciirhss tiwh erfv,e ,eanasu gimi,tonv bpatirilore edae,m dna a.myialg

dDesu nad dt,eutdes tle em tell uyo ohw hgih edyil ahtaPom .Ch -31 a.re .Dr atatrS is the gearkifn .nma

yanwAy, siht is ebrsrviele clel ryiujn beseauc fo nwlgeisl. If eht aKN/ saePTA is tno irgno,wk aN si not ine.glva Na osolwfl raew,t so awetr is egigntt uckts in the ecl,l lgaeidn ot wselnlg.i

Most animoprtt si geginnozicr taht sti' reeebrlisv elcl iryunj - tgyrvehien lese xee(tpc KFP )lol is gklniat autbo lcle hetda

Gdear reesfr to hte ofnritiftdeeani, sahreew agets erfser ot eth NMT odcipernsti

hisT is hgdrhg-iea csaeeub of eth o"lopry tre.ma.edacd. lescl ognriwg in ht"esse wti a hghi :CN airo.t snMea 'sti tgo wol notrnfi.etidaife

Tshi si wgaol-tse cbeaseu ereth si NO EISM.TTAASS eEnv htohgu trhee si vsoinani n(ad usth, a ec,an)rc M ofr eht TMN si stom mroptta.in

ECFREERN:SE

• wogainwlSl
• nuhCgogi

LIEWH NOSIWLAGWL ees( ralyLange roclues omrf wiSlaognlw)

..rt.eu volca flod ceuorls ttha si hte yarimrp lyrhnonlgayeragpa teirpcteov hmcmasein to penrtev asnaopitri niudrg nwglowlisa

• cogLi = lraoNm nu;ctoifn tsrevepn ofod mfor inogg into aerhtac edinast of g.aeusopsh Yuo notd nawt to eaaiptsr ofdo nehw oyu ,owslawl so uyo sloce uyor toglits dan CsV

MEITYLAEDMI RTFEA ONIIITRRTA e(se gnougChi - arphrpaga obatu het msnmaheic of het c,hugo setp 3)

h...Te toltsig olecss mc(ussel nvnedeatir by rrrctnuee aanrlgyle rvn)ee dna teh vocla drsco oatrcnct to tsuh hte alx.ynr

• cigLo = FLERXE to pnetver aiiptnsroa of ronfgie yobd morf igong fretruh ntoi c.hearta

LEHWI CGGNOHIU se(e higugonC - raghappar tabou eth iacmhnsem fo huo,cg epts 5)

e..T.h vlaoc cords lraxe dan het sgtloit e,sopn angeriles ari ta rvoe 001 p.hm

• goLci = To eplh peelx the ifnrgeo odby tuo.

FNU TFCA

r(Fmo laSgwinwlo k)iWi

Seinc the uret lacvo fldos cdatdu dignru hte slwl,owa a itnfei orpdie fo eapan gnwis(awllo apea)n tmsu cneyiarslse kate celap hiwt cahe wllwas.o nWhe ntrilega lisaowwlgn ot tasrone,ripi it has been tmtdseadeonr hatt oilanwlswg cucsro smto tnfoe giurnd pxenortaii, even at ullf nxieartpio a eifn iar jet is deepirx arbpybol to lerac hte urppe rnaxyl mofr dfoo rnentams ro iuqdl.i Teh cialcinl csegnncifiai fo itsh fngiidn si thta ettpiasn itwh a selinabe fo sopdmicmreo ugnl uoncfnit li,lw vreo a rpedio fo eimt, lvdpeoe eyiaorprrts rsdsites sa a alem sosgsrpree

... ehT yspriorarte rtence of teh ludamle si dlirecyt dthieiinb by eht ialslwwgon etrenc rof eht evry bierf imte htta it esakt ot lw.awosl This smena ahtt it si lfyrieb imesplobis to aeretbh dnrgui tihs haesp fo awgnlswoli dan eht mmtneo hrewe gntabreih si etrevdenp is onkwn as tidnioelgtu aea.pn

AF ,0129 P. 40:3

27- ysda ingflwool an I,M tereh anc eb a yppialral cmeusl ruurept, leiagdn to timlar iargrtouegnt.i hsTu the mumrru ni eht snr,wea iyfsecapllic hte ictrodpisen of osloyihlcsot nad caiadcr xaep

In ryoseekau,t teh '5 ygsaeinuehmtonl (7)mG apc si mnpiarott in hte nitniiiato of rlatsoatnin bescuae rticauykoe iiiiotntna afrstco )(sIeF yditfeni the cpa adn ehlp saembsle eth ioorbsem at hatt siet 022(0AF .4p)5

The sebeanc fo a '5 mG7 pca wuldo suth eieurqr a efntfider uescenqe ot lwaol nalsatontir tntiaiiion nad oimorsbal etynr .(e.i na enritaln ilsorbamo treyn s.ti)e

heT '5 dan 3' eaatnstrdlun eirnogs era roem attimpnor in ugeitalorn of rointtnalas nad onatntriime of snlr,ittnoaa yelteei,srvcp adn ierht ceesnba uwodl ton dai snatraotnli of hte ialvr RNAm. hTe '3 -pyAlo atil si tnimropta ofr tcooerptni fo uryiaktcoe NRmA morf giddaeraotn nad igndai in xroaitpetno ofmr teh lcu;unse tis scbenea dlowu tno aid sinaolnatrt. A yvre htosr nope nargeid erafm odwlu not aekm a nnaiigctisf fficerende in iltaiyb ot be sdaetntlar te(h epon ndgeria fmare is eth rpat fo het mRNA able ot eb tldtaers)an.

siTh esnqotiu nca be newarsde by a cprsseo of etinioalinm ahpcoapr ni my iinonp:o 2F2(00A 68)3p

• ucesBea he has tsseet tath m,erodf eh hsa ot aevh the SRY neeg nad thus hte Y omsorechmo hiwch itlaeinmes 6X4X, nda 74XX.,X
• sihT is tno a mrola-ligkonno poyibs adn teh stnqieou sask abotu a rahocmlmsoo atrylobiman so yuo nac eieminlta .,X6Y4
• saoMic aokprtyey 64X5X/4,Y, si asatciosde hwti Te'unrrs y.ndresom sTeeh idduinlivsa tprnees thwi leefam eeratxln gaeletani nad teetss usddcneeedn or erlrya esndceedd iotn eht aalbi ojar.am eyhT duowl ont veah arlcsot ss,tete adn uths tihs ileaitsenm ihts r.eanws

shiT asevle nloy 7,4YXX hhiwc is lilnteKsefr'e sdnmorey nad si aaesdotsci thwi tteucsalri thpyroa adn evsxtinee iiobsrsf dan hztyniaoaniil dnalgei ot ittl.fniyire

woFl tear ( Q) = V * A
-V oeitylvc A - cross ctlioenas reaa

uOr ieoyctlv si nvgie as cc2mes/0 Covetr n sthi ot mnc/mi /c0sec2 m * sso6endc0 = n120im0mc/

Piugnggl ni sith veula tnio ruo oianeutq orf wflo erta ew teg c21m00nmi/ * 2 usraqe cm = 0240 ciubc cm /nim

etoN : 0001 bucci mc = 1 L nda heefrtroe we anc ntevocr uro nraswe ot nLmi/ hwhci rea eth iqeedrur tunis by vnddigii by 1000

= 42. mnLi/

it si coarcht rimea totho deeissa as it is edetnriih nda ihwt loaabnmr yielnm hh,aets toof pro,d hemmar oet tce.

phemioCenl si a EMRS ahtt inzgsanotae rsegeotn errptoces in hte .slhamphyaotu

fI ogenters si dingeaoztan hreet, reeth si ersddaece gtaeeinv cefebkad to empiovr FHS nad LH leaseer to asttelmiu ouotivnal. shiT si evyr aonmprtit in CSOP and eorth seoirdsrd wthi dearcsdee rlteiifty.

gUh tihs ine.qtous hTe raGm sanit adn ppurle made em htgin hptaS auur,se utb it aosl nonismet "dbg"undi nad l"ileiapct"l AS( si a uc)scoc. lidtilnoday,A AS si nto a cmnmoo UIT icfetnnio wilhe daindaC is.

iygnAnon ceaebsu of eth raGm inast adn rpuple treidpcrs.o

mFro oqur:a en"wh ueiorelodrzc is dedda, eth syrtalc tevoil tkena up by etays cesll is eritaden". tWwwodtyane-si-e/muecvs:-pw.yap/eiiioovsgr/--at-clmr.t-r-hocaolseGtaeqh

Fitsr rrode it:inonameli a tctonasn RFTNOACI of gdru is olzieteamdb pre ntui emit i.(e. inotlmiaein rtae si prloitaonpro to het gudr na)ootitcncner

sihT siedffr ofrm rzoe rrdoe amneiliiton ewerh a tnaconts mtanou fo rgud is eomzbtldaie rpe tnui etmi ie(.. taer tayss nacn)otts

In sith n:qeousit

• nI wto ,orhus .52 mg fo 15.2 gm si miezdbo,tlae iwhch is a coraintf of /51.52.2 = 0.2 or %20
• ,uThs ni tnaerho tow ho,rsu troeanh %20 wlli be diebmtloaez ecsni ihts is esodrt-rirf alininitome
• 02% of 10 si 2 nda -012 = 8

A02F02 2p23

geetPsz-eJruh drnmyeso is an slouomaat ntniamdo sredynmo adtaosscie twih ietpgyhmepdren cmseula on eth tohmu, pils, nahsd, nda eelgtanai as well as ceirdasne skir of betsar and IG a.crcnes 00F22[A 37]8p

Tihs tpeitan srstneep hiwt the ciarctcreithsa egepytmpdhnrei aemsluc as lelw as poievsit uoctcl odblo ttes hchwi dcolu eb eidatnivci of an unrdygelin IG a.lingncyam eegtePJ-ruszh is aslo tiodasscea hwti msouuren aahormtasm uoohgtturh teh IG atrtc ichhw lcduo eb soscedaita htiw eht aptisne't areglen IG ommtpssy edu to hiter yaiitlb ot uscea k.ablcgoe

rtOhe rsaw:esn

• Cwdoen sdeaise - ptemluli aamaohtrm rnodmsey htat scaneirse krsi fo ,absret hod,ryti ,interue adn throe ac;rnsec it si otn esdsocatai wtih het gedyemtprinhpe ecsmaul
• naedGrr dmenosyr - lfiamali otuaeasdnom ispslooyp + esusoso nda sfot sstiue mtours
• -eouTrrrMi dymsoern - rera errtydhaie aosamlotu ntaidnom anrcec dnyomrse ohthutg to be a tupesby of HCCNP c(hyLn )monesrdy
• Nrousirsifmeotoba - not oeacssadit with IG ssiseu dan yctplilay aveh a yrve tnfefeird isonrtetpnea 2A0F2(0 )552p - N1F = efatcu-aali- ,tspso hcsil oeunl,ds yomeophocohmct,ar eusreszi, nuuteasoc anrbrome,ufiso c.e;t NF2 = aarlbilte sleatbrivu cn,hsawnmoas lleevunji rcatts,eac emisgaon,nmi mnymaoepdse

Yuo want mhentiosg tath epmirvos rhe osootspresoi, hhicw is sluauly wntbiighreag-e csxeeir.e So vidao hte snwmiigm eon, ceueasb t'tsah jstu erseddeac it.gryva ehT tseb rneasw is anwkgli ostduie eyver yda ttha locud ttenhnergs reh orev .etmi

Fsti,r oetinc that 'etrshe a rdpo in ninoecorctnta efrat llryeeeadhdcgy eahhst3po-p to 1oce.,topira3pbshylhgse- h,suT the cnisoonevr si erimdaip erhe.

,Ntex 'sit smoweoh nierebergmm hhcwi kiefanrg nemzye is vveo.nlid iWhch si epyl-yep-eeohlatcdrhg3ashd goeaeyhnsedrd in teh ygllicotyc aw.yapht sTih is noe eewrh if yuo nwko the etbruasts aenm uyo kown teh yeezmn a.nme

fa 2190 pg 2,66 aioathnnIl jniryu dan iae.un leseq teh talinonhia ruyinj nad qealusee tpar htye yas sideng nasla aishr or osot ni eth opaxrrhnyo gt&;- deeecrsda aticiyvt of ywaira aiicl sa trehe si otso inlrvgoye ehmt dan actn fuoncnti rbptopocolcry ae sah lciasi a(f 2109 pg )663 - aisilc anc rsudipt lpoyseohgamsso and raimip oehscpgrama ;-> dasdrecee eloravla rhpcamaego ntfucion sa ofr het aencdersi scumu tiopurdocn dan cetiesnro - ikd i ifuegdr rteeh si an rtrnaiit nda rouy dyob liwl be tynrig ot lacer ti msoe ,how i suegs thnki batuo DOCP

eHr lcmuaci is ylon a ellitt iehghr tnah oanmrl prepu( itmil 1).02 deu to eht sxscee tvinmai D lspntmesepu ehs okt.o gdnrocAci ot AF 1'9 p.( 07), daecattvi ivnatmi :D

-ecnearssI itntnlaise onsoiprabt of liaucmc and s-puh hrisTsohop- si wtah ienersac ehr lcaumic nrotonateiccn ni eth r msIe-nesarseuc eobn tnraeiiizamnlo loe(wr e)lsvacsneer e-Ils eobn ieorrosnpt ihhr(ge svl)eel

nkPi srod is scdienribg a Grma eeivantg atrac,bie hihcw sah owt bnremsame an oerut amerbmne and na reinn rnmmebae as(wreeh rGma tivsoepis have jstu oen cihct bmaen.rem)

thBo rmGa + nad - btreaaci eavh an ER, can be htbnidiei onofuileoruqsnol gt(hohu anieevgst &;tg s)epvoit,si obth aveh the gldancpteyopi alwl oss(pietiv hckerit hatn sgani,teev) nad terehi acn evah aocaseilhrpcdy cuplsa.es

FA 2020 p. .525

Aslfae-h ospst rae yrpett ogtcipoanhonm orf TCS. hTe ueelnaymbdsp soleund dad terruhf upotspr orf STC

uYo hslduo be ginhnkit fo eomgsnith iekl Ercsoceucto.n hTye had a GU cpeeordru adn nteqesbsuu ccdaria usesi.s

nheW I hera stof S,1 i hntki ahtt the atptnie stmu vhea adh a euiss thiw het olingcs fo itheer het lrtmia or itsuicdrp easv.vl Pnigayl osd,d itsh dhouls eb teh trlaim .vleva Yuo saol eerh an yreal ioialsdct umrumr, os uyo htgmi eb kihnnitg vmoleu rvaelood S3.()

eIllgdiwnn IV thetcersa si a ommonc casue fo essdnmedaiti isacdindsai adn it is due to dnrhaeeec fo het syate to het cttrseh.ae

emmRrbee hatt sedeimdsatni icnonitef amy aslo eurlst ni ipetsant ihwt enaernotpui

CMI unntfosdyci S,(IAD )DISC essespdoirp ot tacsouumocune TNO atiidmdnesse niioctenfs

hisT si a esca of nafMra ds.yeonmr ihsT is a ltal idk "('63, esod elwl no ).edriTn esadL to a 1BNF geen ti,maotnu tcnfiegfa rilbfnlii pote.nir

eioCpd ormf ENBM 22 orf escetnsompel :aske

A" gdoo pci inwohgs numaslooa irsaeetr ni shroohsee ikyned

-Pc/e-w-hihstakharcreyc/sgea_aae-Ar3otoseso/7w9oiswt-9efrin-lfsu3ssnry.1ed-_-foehgse:r--/pt.sgeeptaeociireotnftrrtre9-w13-eh2tacehi"

anRle liparapyl rsosicne is a conomm iipotmclocan fo ekscil lcle eadsesi hchiw wdulo asuec orssg rmuiahtae A02(F20 ,026p 4p2.2)

Gprlleoumoritnesih dlwuo eb csdeosatai thiw RBC satcs hertra nath rgsos ematahrui sscat( aer tpenesr fi ythe ear deelears ofmr hte rsmguluelo or l.usb)eut arhiioepNthsisl dye(kin ness)ot rae tno daisecotas wiht eksicl llec dna ulodw kielyl be eissocaatd iwth ycsarlts of esom rsto no nslrsiyaiu. Pttiritossa ldwuo lileyk nptsree wtih mroe BCWs nda dseo ont clomnmoy nepsret hwti eaiautmrh tbu rterha curneyg nad .uadisyr tiosTlrinaan ellc omainccar si erra in eht niyked adn inianotrltas lcle imoancarc of het dabdrel si eacaidosts pssalnie .tiramaehu

alnldiSefi si a DEP5 hntriiboi ttha nrsu het krsi fo aucgsin ontyopniesh in itastpne no tsetianr ued to het yygesnr of het ecnhmsasmi fo naoc.ti AF0220[ 426]p

tsNerati, kiel tl,yoncinergir rokw by incsigenar NO prcditooun cwhih ni rutn tacs ot ceasienr cPMG in hmsoto cuslme icuangs oionilaatvds. E5PD birhinotsi cat by idcarsngee teh nrbkdewoa of PGcM ni mosoth es,ulmc gicanhnne eht otcina of NO to ecsua staviodol.ani T,ush nwhe noidcbem erteh nac eb yssemcti aiionldstova atht sedla ot ogseunrad .oheopstynni

yFtta Adci airodetgadn
Ocrsc-u in tdoiricmnhoa ro msxesroepio

ristF setp - takupe fo the tafyt scdia by hte ellc dan daindito of oCA ot mhte

cedonS tpse - keaUtp of the ttyaF yAcl CoA llomeecu toin hte oatchrmdnioi by eht atrnCniie utlheSt (* ihchw vlnvesio varolme nad hnet odanidit of hte oCA oumleelc gaani ot hte ttyaf aidc enoc sidein the oamn)rcoiithd

cnOe ni teh dimnhitcooar hte ftayt cdai yam gneourd , ad-tBoxtoeniia ( a psesorc in hwhic a ayttf cadi is e/dladxvdciezieo ta hte aBet anrboc to retangee ltAyec oCA ni eavsrel lccsey )

nA clyA AoC eyshnoreddgea azatclyse eth iiltnai tpes .
okoL uto ofr Hkoyeptcoti eHloapmyygic ni fecsetd fo ftyat adic deiodatrang

ehT 2 mnai eptuyssb ot be waear fo rea a - mpblore hwit eht erniancti stehtlu ( ecymitss reinincat )efc yiencd-i or wiht na cAyl CoA aoedneeghrsdy ( ge ADCM fcndyeicie )

Cna naoeny xneilap ywh coagrpmhea itticyav wdluo be scdrdaeee ni is?th I ednawt ot ipkc oen ttha ahd tohb uucsm tgenscire aiyvtcit sa ebign esceindra algno itwh scaeedirn amgpocahre vtaityic thwi tcctmianono desraece in ayiicrl ctaytivi btu hsti wsnt'a an nootpi so I wten ihwt lal deiscrn.ae Siecn ti's lb-aselstdehliew hatt aorsaphgecm aceus aaemgd ni ymhmsepae piecyes(lal ni roksesm due to tscnanto irtiatinro ormf hte ,smo)ke hwo is it lipesosb ttha haromapegc tivtciay uodlw go DN?WO

aNualrt onirasrfmottna si ewnh eabciart eakt pu edkan tbacelari oohlsoammrc DNA in eihtr rnveeoninmt luau(lys mfor llce )yli.ss A ellc e"tasy"l is htwa semnira of areilctba eegns newh het caiebart si edad (can eb dctxetrea fmor atrc,aibe sa ohwns )hr.ee The HSNi gubs all nca edrougn mraorf.satinton uYo wnok it si fnrmaoatorinst enve woiutth kninwgo hwhci ugbs can od so ueecsba ti s'toend etka pu eth AND nehw saDeN is ddade t(i likls yna fere miranvneoentl ADN in teh eslta)y

ehT ol:bdsgao atroiitnp icotieenfcf is teh iorat fo etcotionarcnn of nseathcite ni het boodl sv. ni eth ulgsn newh a datyse ttase is ehade.rc oBsoalg/d poitrniat fecfnoctiei si na pexsoneris of lisbytuoil of eht rdgu ni pasl,ma adn sels lbuselo eagnts aehv a setrfa tf.osn/tefoes

ACM immu(inm oaaelvlr nocn)iactntore si eth otntonccienar of eicshenatt in hte ulsgn ehewr %50 of eth apnlopuoti odse otn omev in nssropee to a ugriscla nrasrtdad uimsu.tls It si uagsoalon to ED50 in etrho saear of omya.gcphorla MAC si rdencsiae whti cngdeaires slitylboiu saeeg(ircnde sl/oobdag tipiarton eitocnesi)fcf adn rcdedseea cnt.pyoe fI oyu ihnkt tuboa ti isht loduw emak ssene cebause fi a rudg si sels seoullb ro ont as toe,ntp uoy hvae to imdrsanite emor fo eht drug and tshu wldou ehva to aehv a rhghie iinamlm aeorlavl nciaenttcnoro to ees na ftfce.e 0[2F02A p5]49

TE:NO MCA si vidadiet os if oyu imx otw sesag at 7.0%5 of tierh ,ACMs uyo tge a oltat 1.5% .ACM Tuhs rfo eth onqtsu,ei ouy rea tenlayelsis mntidigrianes teh esam OTTAL CMA ot chae rogu,p so it si tno eht fnfedercie ni MCA ttah si snagiuc eht ffreeidnec d.borseev

ehT rsibagan: ptiartnoi citfnoifece, eomr lmcnoymo dlealc hte i:gaols itpirntao ctcefnifieo, si esud as a sterragou orf hte ontamu of eihstectna in eth biarn and oecnrropssd ot idlip tyull.oibsi CNS usrgd muts be dlpii obeulsl ro atliyvce ao.spttrrend sA hetes ear nidaelh thns,eicaset the piidl uoiilysltb ltlycaau deso ton lytrgea uettnrcbio to mtei of tsoe/nseff;ot eidatsn eth lpaams ytslubioil si het nliitgim trcofa. gas/liO ttoianrpi incciteeoff odluw be edasoictas wtih het rdug ctypn.eo

leurNa csret eclls temigar ot mofr eth ainoolcutrraoypm pusmte and lmairsoinabet eaossacdti htwi relnau scrte omiragtni in the rateh cdleuin ttoelrogy of fa,llto nnsrastiopito fo hte agrte srraieet, dna enrepsistt nruustc ssarur.oeti Fonsiu of eth tprmaoiocruoalny emuspt ihtw eth ucmlsrau enacvriltru metups is atwh ofrsm hte uonsmremab ,pesutm so tstepani iwth a senpteisrt sucuntr trasueoirs liwl hvae VSD as lw.le 0A2(F02 2)80p

ncniaoF oeSmrydn
paeI mdri enirtsporbao of oieatncabrB and eorth cpmdouson in het liPaomrx cdotnovelu Tbuusel ( eg aoimn aisdc , oguscel ephaphtos )

lCciinal rFeutesa antiiV:m D sntsterai oyhpetpciHsaohpm /oaiclaimekRocttasse

Fiaonnc nermdyso essrtnpe whti lrpaimxo nelRa aruuTbl dAssicoi ( anlorm naoin gpa amctobeil caisidos )

IV laonmr lesain lwil sareicne tdthioyscra ueserrsp ni eth .acutuseralv isTh iocniost uistnloo si fyelre rdteilfe ssorca het lai,eapcirsl whhic is ecdotllce by paiymtlhsc and acn be dkipec up in this mipentree.x

rneoipMh itemstalus mu odipio ctrrposee ot repodiv teh iddeers ftceef fo anaislega, tub ni ndgio os nca asol itcaerptipe mayn seiddrune e.teff cs iTsh inttape ahs tmlplieu sgsin of oodipi icyotitx, ldicnniug oimiss ie(, tipoinpn pui)sl,p ytrrirasope esorisendp cddivee(ne yb lsow ioryasrpetr etra and ypaitrrores c)idosasi, and CSN eserdnopis g(,e esnolnmceo, o )amc. Mnerihop si maiyprlri bezdmeialot by eth rvlei vai cldungntoaiuroi to mfro 2 jraom taltbeseoim . ehTse atistbemol,e eogroeciup--mlhnrndio3 nad e6mlrohpgeocuin-odn-ir, etnh grnoude eanrl itoilinaenm aiv eirntxcoe in the ei. nur eucBsae the betlsoteima are mcoilallatybe atiev,c alenr fsciytnundo cna edal ot aetieltmob uaocnitlcuam adn opidoi xocy ti.it nrieidMo-ehonrgol6ucp- si rparculaytli epsbesinlor for ictotxyi, iacgnt sa a remo etopnt um opidio errtpoce gntoasi than oinerpmh itlf.es

Due to tis alybltlacoeim itcvea adn neyallr delcrae sbmtloteea,i ohnpemir eriqures acuferl tingmiroon nhwe eusd in ntiatsep thwi nalre s o.nudifyctn hnWe ioidop napi rolcton si dndeee ni such i,tasepnt nynealft ro edyhhrnooprom si nfote rfeperrde sa heste gsudr era mryatpenlondi hcplailyate eadelrc.

Seur:oc 6U8W153

hTe owt ssincteo fo eth pnrenho toms cptsisebleu ot ipocxyh iditnncoso ear the 1) moripaxl olocdventu tbuule nad hte )2 TAmL erudmay(ll noseitc of eth kthci sdingaenc lpoo of e)enHl

hTe semt si diircnbegs lbluosu mdiephoigp, iwchh creospdu gGI isabodntei omms.edsisehmeo P(V is IgG bidnsitoae nagtsi e-e1dnslgiom dan -esglme,3oidn ni het oral .uosmc)a

PB ocresupd het sente iberslts htat hvae a egvenait Noklsyik gnsi nt'o(d ueptrru htwi ub)i.nrbg siTh is eeubcas rh'ytee euaismrppled. usrrSdpei they id'tnd ask abuot demmssom,sohiee tbu I thkin atth htat hte BP etgnnai is artp fo the mssooememsedih dna usicterr eth adbaniousi.eott

heT ernwas is ussecnraear uecsabe tihs si lla amrlno ehbir.aov Sshe' lnyo rdones IEWTC in het psat yrea /w on itemday epinsseles ro thero leprsobm.

It uwnltd'o be a lesep luaonjr eaebcus ti doluc iplym ttha sgtnomehi si wn,gor btu teerh 'sitn. sehS' 72 dan fi ahgytinn ehs dolhsu rduegap morf ehr huadbns gpcomnailni oubta hnntoig tirnam.pot

GIg nsoetiiadb nca ocrss the penaaltc, iadngle to rihtyod ntl.rmeenaeg Tsih nca losa nipealx eht srridot nad suessi with iisoranerpt in the ebrnwno. Etanyslel,si hits si sncaigu ltoneaan avGres sieds.ae

oFmr Dto:eUapT N"atnoale asevrG eadsies seefrr ot teh dtyerrhoimyhpis taht si enes ni a lalsm pcetraeeng of anntfsi rbon ot ermsoht twhi eGrvsa de.esais gthAohul eatonnal rGeavs ssdeeia si ysalluu silm-ditf,ele it anc be esve,re veen lhtn,arge-eiftein nda veha eotdelreusi ctffees on eruanl eeedv"tpnlom

dGoo eoapnanltxi no itd:red dos.a5sh8or:b/nt1eqmae_aesnbemdi/trap_opovwgtrs_jdyw__h_ywndt_/cco/cee1_lto/m//ei/cp.idnh6e_tmwty

eE,slAnsyltai = imcusoun algdns (myfao myaBlspoc) t = plaietra clsle insa(t ispeiln,ocoh P ra I atle sllec taisn IPnk /w a efird geg paacepera.n nAydiltol,iad yehrt'e eoabv fehic sc lleC = cihfe lecsl (tanis coblapiish, ueprs a,kdr nad lewob lraeipta lcels)

Li anemiFur edosrymn is dscstieaao htiw a sols of intnucof oiauntmt ni p53 002(A2F ,24p2 )46p

53p is a atldourom at eth G/S1 rrseiticnot .toipn p35 tiiatvocna in hte scpeneer of ADN aeam,dg emfdsdoli trn,iepo and ixhypoa ldaes to ianotcavti of X/BABKA adn uetsnqsube vtcanioati of het itpaotopc atywpha 0p8).2( hTus, slso of uitoncfn fo 35p lwil dael to ediiparm oelruatnig of oositpasp dan uieindbnthi cell noiisivd in nrceca lclse.

iL iuneramF rmyoneds is asteasdioc ihwt ptmiulel urtosm at a ungyo gea SA(LB - sraoc,am eatsr,b ekumil,ea a)alnrde

Tshi si urtopagsdeo yesmdorn ihchw sah odbenaiist iedcrted tnagais lvaorlae dan meglarroul maensetb mneermsba 20FA2(0 )956p

Teh eky sihnt :rae

• ungL nmetnlievvo
• encesrtC aotnrmofi aiiingcdn t( lpidyra psrioeesgrv cs"cit"enrec puotoihlslger)mrein
• L""nraie dosetpis fo gIG nda 3C - isth is raaccichisertt of uotosrdGpea beseuac teh anoesibdti aer ot het agolrrleum bnaemtes emabenmr so tyhe pioetds lla agonl het oulmrleusg stbmeena emeambnr glnidae ot nerlai lmnmu.eoescenuifcro
• rbeRmeem tath hte ehtor amni euyil/ngknd tboin,mcinoa aagoosmsultrin htiw stialpny,oiig is caiPu uienmm hitw no leucemfnuroseniomc and tyeh lliw uysallu imennto ACAN