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ANDREWS OFFICE PRODUCTS CAPITOL HEIGHTS, MO (K)

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'111c bnnrlal ul ('r11 haduFy Klt!/t7.'N.1, quleu\I 140147. ( NM•r \oppN(: Naliunrl In\/iwtc\ sit /k.llh aal Anlr rican (:Irnyr S,y'itly It,an 11/e IAp:/rluk•nl ul ('rIl Iti,A++My• Nrw Y.NI IInivrr\ily Ml•dical ('clller, Ncw Yllrl. y K1/7111.A'll(/N /(NI) K(11 /.111 (AInNYI.&lli l'1'('I.A11• ('Y('I.K'tiMl' /N VA\('III.nK KI.I.nXA11(tN lhrcc cla\v. 4.1 va\.kId:NIN\ na•dl.pc their cllcc/. 1110110110 tht :n11v:11aN1 .,I yuanyl:NC rycla\t arkl lhc iM rca\cd \yntht.i\ lll c yl bc (:MY NNrnv.wkhlah/t\ \ul h a\ n/tr./Klycrrin, ndnKwu\\Itk • hydruayl.slmnt• y/all'. l'll• . rl•\Uh in 1hr /,'l'M't:NaM /II /hl• nllrll' n{Nll.• Irel't:alk •1I 111411.1t 1lvJll•\ /IIe \ yhN1+I1N INt11/hIC) /Vk'n/yllle IINIt/,/I r11•/ny IaNr ry.ia.a (llt\t alecrl/\ havc hrca u.clul /n IMrra\IaK .yllk• (:MI' \yntlk•.1. /N I h1 65100 7818 1i

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M AnKrk•an )lwrn.J l.( ('arJlx ImapinK 101 2J2-2t1, hrly ly1(7 Other .ul.lant Ank•ncan II[Vfl A,MtctalNM1, rennsylvania Alhliale, and lhr Mary \oNlh I4•:.J 1'ru•1 I n•m llN 1>, ~.lnne'nl. ,.1 Anr.lfK•.,a anJ Ilnahenu.lry/lll,q.hy.it'.. Itnlvr/.ry .d I'. ur.+llv.m, . 1'Inl.ul. IL1„ , rd, 1 / 1 (Y1MI'/1KIS(1N //I A'1IIIiKOS('I.I'.KOTIC 1+A1(/NS ANI) I11)1.-I.11'll) I IiVF-I S IN MAI.Ii, I I MAI.1:, ANU fh\'flltifliK(/f~l.-IKI:A'fLl)1-1•MAI.I: MI(7i I K(/M SIRAINti (-S7111./h, IfAlJl/r, AND ('111 In /vrlk•r tr, drlcmmnl• whrllk•r Inak aml lirnak nlia•c Jlllrrcd in I IUI. hpkl kvclN lN in ,Illk•rnx IcnNic rr.l>,Nl.c NI a high /N Jk:(, we c><amlrrcJ.1 inhrrJ .ttaln% whk h drllrlyd m.ua•t•INlhlhly lu llhrr/ha knla~;('S7N1.l6, 1I/U.11/c, and ('111. Mk'c wcrc IrJ rnNm:d llNlw /N an alhrllTrnk• diet clNllaimnR 1 2S'{• chl.k'.hYl1I, IS/A• Ial• alkl 11 S'.( l IN/IN' :N'1lI I.l'\NNI 11111111\Y a1kl \//e Wrrl't(eler1111111'd aIICr 1-8 wrl'k\.m IIII• JN'1• pl•Lma 1/h1. hp/d kvrl% wrrr lklrnmrlcll al t/:uk) J wlt•Iv. Im the Jlcl. I"IN (' 1I1, Ihr uk..l a/)Irrnx•kN1.i.-rc.l.la/N .Ua/n, 111)1. lipill Icvrl. wrrr vrry hll•h arkl/kN •dlrt trll by .rt tN dlrl hlr NAI.N/c,111)1. Iq+NI kvel, wcrc intrnik•dlalr Ix•Iwrrn 11k• lNhrr Iwo./raln. Mak kvclc wcrr.igndil.nmly higher than Ihr Il•m.llr.. alkl IIk• •nIk'rur.rnk• d/r/ t an.r,l a dnlll in 11111.-Iqwll kvrl% ul 14 - 2T>:- lkpl•nllu/r. lN/ x•. IvN ('S /I/l.i(*, Ilk• I/Nh1 NIk'/11xlrnN/~ \YxYlNlhk %Iraln, 111)I. Illtk/ kvrl% wr/r law clN1y..IrrJ lu Ilk• lNhl•r Iwn .Iraln.. M•Ilc, and Irnlalrl aNl nlwmal chnw d/li IkN Jd1cr nl 111)1 l/pk/• INd (rnlalr..hllwa•J a54'; lhvrca.r in I IIN • wlk•n /rJ Ihr a11k•r,. Flvlk dk'1 ('lN IrNtl IIA1.1(/c anJ ('57111./A, tl:al..(rr/Nl<IrcateJ Icmale. rrx•/llbh•d Ilk• m,dc. IIN' 1101. IyNl1 h•vclv in n/k'a• Iln alhcr/lieenlc Jlet dillcreJ uvrr a 1 Inld r,ln/,•r a11uN1ir IIk' n/lk' ~.'rIN1111 Whrn 111)1.IKNII kvrlc werc clNnparrJ In Ihr nu/lltn•r ld adk•r..a ti•IINk- k.kNl. IN dlc kual k.kNl arra, a high degree 111 a•/Nrcl,ui.Nl wa. I.h a•Ivrd 1. - (1 45 hN k.km nlmlhl'r :IrNI -(1') I hN hMAI h•mNNI a1l'aI I h/. .ul[Fr.l. tIl)1. bpkl kvrl• arr u1qNNlan( in ik9cruupinX athcn.x•kn.a..ux•cplhlluy in nuar I'urr.•n, 11 . Ilnlnk•.• 1'. A . MAchrll, 1)., arkl Alhre, I). Alhl•nnckroa. M 215 221, 1Y117. (MIk'r x/p(NN) (':IIIIIMnIa AIIIII:III' 11f AnlCrk'an Ikarl A%%nl'Ia1NN/, Na111MaI IICan, I unF alkl Ilh.wl In.ululc cnkl NalilNUl In.llluk.r nl Ikallh I aan /lw Ilnke l.y./n McnNlrial Ke.ran:h ImINwalory, (11i1Jrcn'. 1llhpnal McJkal ('c/Nrl, ( /,J,larkl. ('A. 1 (iIiNt:l l(' ANALYSIS t/1- MIIKINIi •S"fKA/NS ('t7N1.1h) ANI) ('111//rc) •f// (Y 1N1•IKM 'ff11't MM' I41SI11( )N (1F A!h-/, A(iliNl: UI:11:KMININ( i A"1111•.K(1ti('LI:K(1SIX til IC('IiP1'I1f11.ITY 14rvi1N1o rc.ull. .urrr.1eJ that slrain. ('t7111.//Sl and C111/11c1 JillercJ in a .inKk gl•nl• IIN allK rux'knrciv.u..rplilNllly, ca1kJ Arh•! . ha.ed lNl dala Inlol rcclNn hlllaw n/1NrJ .uain. Arh I wa. Irnl:Mivrly av.iRncd b.M/klk.ulnlc I bnAcd N. Alp 2 h/1h1. /r1aNt, ac1...a h.•Iwrrn ('57111./A anJ (' Ill/lk) wrw cameJ /NN In.N.fr r 1./,r.1 whrther Ilk• Irnlal/vr n/.lp Ll„i1NN1 wa. currrcl ParcrNal vrauy, anJ /, anJ 1•, Ilrnl;a•ny werc camrnrk'd ~uxcpl/hlr ullcks IA Arb•l, hNml) m C'17N1./h, we a.wrtialaJ wilh rrlMllvety hlw kvclv n/ high lknaly hl.qlnllein IIIIM./•a1N.k>Iend in aunlul. led an whenlgl•nie JIr1; rr.i.lara allrk+ uf Arb !.re aeMN:iakJ wNh relalively high kvel..d H/)I.-chldc.ltad 1•, prnKrny have 111M. kvels that xe in(ennediate hclwern thc.e n/ the Iwu rareMal %Irain. A/nlmgIhc I-,pn/geny. Alp 2 wkt Arh d nnern•Ka1cJ. INUvId- mK clNlhrmal.ry cvkll•nl'e thal Ash l i. liai eJ lu Alp-2 an chnNnlvwNnc I I hrre mk e n'alNnhinanl I/N Alp ? a1M/ Arh I wl•rr (INMd anMNlr Ihe M1chHNINMNIK',o Ic%led, rYvInR eT

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Awl .u41•IN/1N111y i.l .111N•t.Nt ICL.\1. ./lryt••n 1111w• 11CICf1Ulr11•tl hy iht• \:nIN• )YIM laN by Iwu 11//4•ly Inl\iJ )lfnt'IN I.wl.a\ Ihdi :NC a Nlaaunun11.1 1 7 ICntlUalr'dn\ al.atl i I hl. yc/Nt wr% n:lllw•ll Atll f• IIN :/IIN'h/41itIN1\ \U\CCIN/hlhly• w11I1 ]III'It'\ r IIN H'N\I•Ilwt':/INI 1 IIN \/14l'INIhlllty Ash I 1/1:1(NIMI IIfINia/MN11C I IM.':Ir All. '• a I:clw• l11•n It1•ICtnunC• 11w• .ttlw llnc /ll Jlw/bp/11tlNCin A 11, /NIC U( IhR 1wu n1:/11N ININa•UI\ LIu1Nl in 111)1 Ata 1 1. ck;Ulv 4•11•II:IhIC ItlNll Alll Z, Nnti tllf th\IJnCC Iktwt'l'n tlw'\t' Fl'tM\ 1• (/ /l l t'/11/11NNF:111\ w/1h J\Ill1NI.1f/I Ct1.N I/i J? l cnhnaNpan\ In hanlan\, icvcl. ul 111)i. J/c 1111w'l11t•(I :NwI :Ill' 111vCf4'Iy l INICIJICII wlih :11h1't114•I1'tU\I\. I:Nnllr•1) hYlttalllll:dqal ININCIntyw.l l\ ;1\4nlatcJ wnh hq•h Icvrl..ul 111)1. chl.ic•ICrul atwl lkarca..d tl./• ul Iw':Ilt II/4':14' 1 hl' hll/ll•In IIJ/I IIIN'INNy(IIl:1IIy tc\t'nltall'\ Afl1 I in 11w IINN/N !'.Nxrn. It , Mlh hl•Il, I) . Kruc, K• MlNrl/w, A, Lu\i\, A/•+Itwl / iltlw•ul. K(' /'Ill.t't'dull'\ 4.1 Ilw• Nd1/1MJI AlNlh'111y 111 `lNntl'\, II%A 11•1 11t.1 l7(/7, Iu1a' Ilnl/ 1 NIN'I \Il/aiaNl N•NIUN.II I la'•111, I IInF! JMI I1ItNNI I/NIIIU/c ]M.I AIIN'l/Can I Il'LII A\\.N 1•1 11NN/ 1 1..114 lla' Illu.. I.••n M• m.•rl•d K.4••u.h I.AtiN.11.1/v. ( I/II/Ir1'n'\ IL..p11:11 Mrdl.al 1. IN• 1 11 •11 n..l /\ 1•• 1•..Inr .•1. .4 li1. •Ia .ua Ind k1a 1.•i•1.•Ir.I•y Ilmlil\dV nl t Jn• .•.• • I \.. . 1. ... 1 l.. ..•• t.t.•...•. n.1•..a 1/•. I••1 J 1•.. I.. 1'I A l l l l f A( • I I V A 11N1 ; I Al •I I)K 1:1 i L("1 \//N IIIIVINI 1'l lt M(1NAKY AKII KY I NIx111111 IAI. ('I'.I.I.S I INI.NIN'I1.11 till, 11 (\) Wt'tt• I4.L/1tYI 11.1111 INWI/w• INIIIIwNi:tfy :Illt'ry :IINI 111.1111 I.IIIw'1I /11 LNIF Il•1111 111hlllf 011 h'.N11/11F a.N1/I1N'/wy, I.(•\ IaN11N1I a lh•If•Nla'11,11t IINNI..I•1\'l'1 1 hw' INN11 •11Iff :III.IIINN11.1 I IIM /.Idlclt'I :Il lival//lg LN 1.N II'.\I 1 In dN• 1•Inw111 nN•d/n•n, 1'('. ulwlcfwcnt .IId111.N11' 1h:111F1'\ in \I1•11\' 110411 (IN'If 1aN/11•II IM/I\I'.N1•II IIaNI.IN.I1.Fy 1.0 IINNt' ChMIF•IIIYI \I11n1I1C\II:II\YI IIN111\ M.NI' IN.1 nlNnwirl i Ilct 1, wrl.• a•vwlcnl In Ilw• I+It•4•/wl• ./1 1/ (/IM 1414.06.1 12 nlyn\I•dl• I 1 ,N ll•11c• 11'M ^ I. •1 IaNt'111 .N IIV,dIN 11i (' I.N1.14• II W1\ IIN1/wI1I1,11 :11 l'INwI'/111:NwNN II..NI III " III A1. 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NI 1.410 GI4'\, :III/Illll IIN IM.IMaN\•ICINII WN h/Wl'1lYI Ilnl'IIIIIII 11N1 NM/ ( hu d.N.1 .Iq•Fc.l 111•11 1'A1 IIIIii.NINN1 w/dl 1:(' k:wl% lu an aph:ttrnl /i cwI1CIN'tltN IiacIN.N I llt'4'/IVI//.IINNI III•11 IN..L:Ihiy ;wi. V1d a(.IwN/.IwNyLNNIn IIN'lh,1N1.IN Ulv/dvU1F (' L1 /1•NC Ilh IIL.IINNI uI L( I1N tl/ nuoulc% wllh /1 1 1 11 nM 1'AI' tau.cA ullubuaNl ul INNII IN.NI•N$t I111 .11NI 1I111N111at1\•ItK IN1wItNINN1ISS :11wI 7St.l • ft'\INY1/\'l'I)1 11NI11:11111F (II•1/ I'Ai :w 1\ •/I •/ Il'tiI k+N1nINN/ III hIIII 11•IlI1WJy\ I/I (U;w h1111N1A1t' I/w•I:dNlh4n SUn11.11 avu11% wc/c uM.nlw•111NnIF PMA il/ I IIM/ hul twN wItI1111NN1w.) 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INVI 11.V1,M1•NT IN VARII/l lSINI•LAMMA fUKY I'K( X'1.%'SI:S M.1.1 l'r11. I rlwH c1111c1rn11i..ur .ilr+ may havr thllrrrnl hi.hlc llrlllic at, l llr nlic'.d. a11J Iu/NINN1.7) p/.qll•rl/r.. Whalrv~Y I11r hJa. I/N' IIN'V• lh/Il•n•14'l'\• IIN•y 1110.4 hr i/uplN(;nN /u Il•rnlne uI Ihl•il hN.lar/r vll,'n/hl';nK'l'. I'1111N1/!h IIM'lt tlll•IhJ11N\, 1161d IYII• Arc IIIWoIvIYI In u1Jny J[I/rtC11t:ICINr iM11/l'ININIh' 11111.1111111A1INy 11nN'l'\y9 '1In'y ;Nt lu Ik•IJylvl kyry•ra•nallvily• uonlr.kalr hyl+rr.rn.divily. a11J /n k1a1111kwn;NIN1.Ir:N tnNl. IIN'Y l'JN 111111N'/hl' 111/.11•.q yl.hl%. CIN•/INIIUIk•m%• a1NI /ll;lny.PIN91% 1111111/11111N':N1Ntly la w•vl•rJ1 tldlra•nl 1 J/N1 II t cll p.nhway., In //NYIINNI INIIy n IC W t•IICl1.. MJ.1 l c1t. JL• /Ilvalvt•.I I/l /l'Ir.In IINIINhn/,• (1M/IIIli0 IIIIhINI/l :/INI 1111/1N1\ 1IN'll 1'/11w1I1 011.1,0 Ilr 1111I1n•/N lYI by 'I a cIl /k'l l vl'II I,N /u11. 1C wrll :N Iikl.lr% /kT/vCtt 1141411 (Ik r1/11IN' huln. 'lhry JLIIrJ/ Ilql h.• Inb1/1JICly invlllveJ wnh nl'rvr% anJ rJn hlnu ://tly/rnl IINn 11N/1111":qNNIV Wilh IN'tlnNlrv. l'%ftlc/://Iy /1Nhc l'lNN:11111nFr SulNlarn'r I•• wllil b lau.r. all lylr• /d IuJ•I.cI1.1.1 Jl FranulJtr Ma.t crll% nuy 111rrrl.wr :N'1 Jv fC111raI %Wlll IIINqII.t% (r•Iwrrn 11N•.ra1/Jl /N•/v.N/..y.lrm JnJ nuKtJlwr. aml v.ak crll lylll•. In wllanlnl./ uNy (IrrNv..r. 71 65100 7823

ININY nplrNl N.Ihun.ll In.lnNlc. u1 Ilc.lllh I l..m IIk Ikp.llunN•nl uI 1'.ahnl..Ky, lltnvl•raly .d MIthlFrn MrJh:J l't•nlcr, ANn AIINN SI N\11KY NI KVI S( IINI AININ(:l'Al'IIYKININS /1NI11•GNI' IN IIII•. I IIW/ K AtKWA1% I UN('11ONAI. IMI'I.I('A11()N1I()K 11K11N('11/x'1)NCIK1('111IN. VA\//1/11.KfA'IIUN ANI)/'I(t111'IN 1`( I KAVA\A I II /N An mvl•.h/•,IILNI ..I 11N' lI1%ItIM11NN1 plh/ INiKin /d 1/N hyAlnul. ulhl ('( iKl' I 1/t• vr.dr.l Ih,N C1', NK A,nhl NI'K.ur tokt alv.'J wnh( t:K1' I 1 tn IN•tvr IIIhY..ulydylnlt IN/NN 111.11 .n.rah Inu.t Ir, t h.a• lu .nNl w/lhrn IIN' IInIng l'INIIh'I1/1111, anN1/hI h1.NVI v.•.a•I. ,1/h) ./11N/1NI I1M .11 Il.h Ih'..hfINh111aI /,':Inl!INNt tl•II\ 111 anl/ll•1/% a/N1 nlan %I' tK a1N1( '( :K 1' IK w t•rv .J...IN.'~l'lll III IIh' .:Inlt l l•II. 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J:IIa .III.INNt (Ih' INC.cIht oI SI' I:/NK A rtycphw% iN hnlmhlal .IINwNb IINI.t'h' nl I11NI1 IIh' j?IIIIh•d INIr a1NI /N:u1 ('(iK1' 11.111 INl l'Ill't'1 IN1 hflNh'h1al NINMNI. 11111N k'. /h'l1lh't /n 1Y1'.. INN or wt.n. Xuh.1:uN't% kmnvn III :N'Itv:Nt .rnvlry (' /dx... .IN11 :1% t:111.Jh"In amI t'IIN'1 • l aUV'II (tnNN INIlIN1.ItNINM in MMnIJ1/;111/1l'a Inl!p hIN 11.4 N/ y1n/N•a I+IF% plt•trt./1rJ wNh t a1NalC/n. Ilrlhl'tIINNtI ltte I11.1a11111h'-I/hI1N'l'J MINh tht l.Nl.lllt INNI w:N rCJIN1'J ./1N•r t;ql.awln IrtaulKnl, .uFlec•NnK a ec1.NNN1\hll/ hl'IwCt'n Lhhy1.111/11. rl'k•,IN'J ILNII y'nwNy m'tvl'% nINI ININNIMN'1NLIININNI 1/hltNl'1I hy IIh•..• ILmF LL.Y If.•MIct IhlwnN•Ity, il w,1..INlwn Ih,N v.r,J INYVt .InunLNN/n nt .IUUqNIm-cJ un.liNlN•tl ./n wlNqNlll r1.1.1:NN 1tININVl brNN11/rlalnNl. Illlf( /.1 whN i/ wa. lf/II INl'4'111 .111f1 hl':/INh'nl w1111 Ihr I.'anFlNlnit' hkh'llmr aFcnl. chhM/./Nwlalolnt•. (',1r..IK In :h'fIM11 dINI1/11hCally J~IIN'J l(.KI' a1v1/1Nrta.elt IIN' II:Nhtal hkrNl Il..w IN t II/...IININ•..N11-LIIrd INIInNNIay arla'r/c..uKKc.l Ihal t:N hylllmnm am) ('17K1' wcr: t'11111INN\Y/I 11/ rCIJ\ v,1N IILN \IIMNdI/111t/v'k', Ilhhtalll/r n 1a111yl.ll/ln at'INNI v/a ti1' 1't NK 1' 1.../a.N. I IN• IN.a.ln r.n..va..d~nn /n tlh• 1.40 .Nlw.ly. ..•rn NINNI t•t(...Wn• 1.. t iKJ1r11: .nN.1c w.l. J. 1. n.lrul.N...q•N Idl..a. wnLNN•nh ul 11h• wN.kl' IN/I INa.n IIh' IIIlIN//N' I In.l•ItCCI w;1. [IIw.Ii.IN•J /11,ininqll.INClrt'JtCtl wNht':1(NaNln 114 by 1 v:Ilhuln/•uauun 1.1 XI' an,d..ylh'. w111/1.NIlyA/11111 JnL1j!4N11.IN IN111k1th'., ]IIFrI'.h11F 111.11 6Nhy/.min Irlr./.r ILNIa N'11..N V nt•tVt'. 1% a rrt'/l'1111N/ll' Il.r IIh' l'NII:Wa.a/NN1 UI III;N t.Nlh.Ifl'nh'• 11 tlh• anw,1V NIIN...a Al NI :I/hI I!,t.11N' IIINt' alMl R:IIwJ ININI'l/1 l'\Irava..IhlNl lo tht k•wrt :nlway. Ilh• Ir.utn .u}Fr.ICJ thal :NNI ImI1NrJ abway elkncl invulvr.l MNtI V•n.INV IN9rr. ;11h1 .NIN•f IIh'th•In1.111. Jt•14n1I111p! 1N111N (MI 11 L lulhlu.k•J 111.11 IrqNdatnN/ .d .cILINy /N•tvt. in Iih klwl•r allway% t':ul Ih• v1.11at1/CJ JIN' In /IKII c11111C11t lll .ItYihc Ir•pll.k.ll:h'hvlmnt. aml (Y:KI'1 arNl al,l..Ih.'J ,1\ ht'kNlFl/ll! It. IIN• ('hhl't FrIN111111/C tIt /IN'1r V•n.111V11V 141 l'aIl'.:INIn I/N'a' I~ •INNk• C'.NN,In1//1Ip cdl...lll l/l M'IL/llvl' YnVlry /N'evtd atr x1/va1rJ by Irrll:nn alnndl .uh h.1. cll•,Nt'nt .nNAc, a•dN•1 a/hl w'hl a. wt11 r. hy hl.lunnm• +I/hl Iw.dyAlnlu iluhal uq' hINI1t l'1111.11/1'lll'RP.:u1J hK'al rrka.r..l 5P. NKA a1Nl ('GKI' 'ellt.r prplNk•. UN•n mlt•/:hl w/lh .ItY1hi IrccIM.N% nn IarytY h.uN•% k':h1NIF lu va./Nh1aLIhlN1. IN.Nr/o l' Rt1,/vN.,N/1N1 :IINI IN1NhINM.N/.IrN'INN1 M.1t11n1F, C K 1l wlJh.vK, / I Atla 1'hy.Nd./yn a St:uNllaavN',1 1(IN %f.11 157. IY/(7 (h1h•r .NppINI SwrJl.h McJlral Kevarrh ('.NaN'il, SweJi.h Tuh:N•cu ('.Nnpany• I'chllm am/ Augu.ta IlcJlu/hl. Llum/a1Nln, SweJ/.h S.N'irty ld McdIC11N•. Swrd/.h W(wL I•.nvlnNmh•nl I ulNl, a11J I1N KanJln.ka In.InuN•. I I.NU 111t 11.IcnInN•nl ul ('harN1:N'uk/Ey, K:IrlJin.Aa In.tllutc. SNN~INdo1. \wclll•n NI'.IIK(1KININ A IN ('AINAI('IN SI?NSI'flVl: NI:IIKI)NS l)1 1'/ll: (:UINIa11'tl: tN1i-K/()K MI•.tiliNIliKI('(iAN(:1•1/1: AN AUI)Illl)NAI• 1N 11 A'I IVI: MI'.I)1A I I/K 1•(1K "1111: Nl NV•( lll N.INI:KGII' I:X('1'1 A I l 1K Y P1)Sl tiYNAPI l(' 1'( ) I I:N'I IAl. 'tllc prevmr ld /lcunl4inin-A likc inunamlrtartivily in Kuitra pig Inicruw Inc• .culcrir F:Nlllia wa% tklct'ICJ by raJilNnNllllmla..ay ptlNtYhln'.. 14c1/tat/nK Ihc ani 111:11% wllh l'a1NaN 111 7/Iay. Iftult 149 t;111Y1111en1a1NN1N rtY11N'lYJ IIM nwan t .N111'IN I.t IK unlAinin A Id,r imnNlmwcx•tivl/y by KY1f• /nwu il% n111trN1 va(Ik ..1 IS11 / 11 1 hlN/l Iwt Ka/1Klnln lhr'h lovrlllrNlanrt IiyuiJ t'hnNluH/fraphy tcveakJ 1ha1 INYU../ mlu A IIAc inNlwmlrcacllvtly wa.lN•Irnp,r•mluN a, in alkhtilrl lu nrunikionl A. It•a4% tllttc. pNNhllg h/111C a1111.111h/an 1:N'hyA/nin ckdllan an111N nCUr11/N'INilk K wCtC .ICLY'IcJ, and IIKy t1t11 wert tk'111tItY) by l'a11NaN'in. I'.IIYYnlllhy\Mlh/l,`KiI t1ullN•. .Ih/wcll thal m'INnk/n/n A appINYI l'l/hl'r by .u11cr1u.Mln ur by prc..utc ej.ti•Inln cv.d,eJ a.h.w Ik•IMllal/a1NN1 in /IN• /I/a1lNlly t// Inll'rNlr Ilk]cMctK F'a11/,`ha m'utlNl. In YI/L. Neuru- INmn A eW.1.eJ tk(h11a1/~:nMN/. In IhC n1:IMlrlty UI I:ell. (c.h•J wCrt awN'I:NI'J w/dl a u/11,1II /mIt'aV' 1// I/h'IIIlNn/h' //IIN/I ft'N.tWNt Ih,wl'vl•f. Illl' te./N111.t% wl't\' llhrtyM'1/ by nM nllw.llw hY1r11r.LnIr:NNN/. 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INna'LNh.h Ih•aIaNIJ4• Su/lerurek d/.nNILl4' p.NCtll•J hNh 11K .yn;yNN' vrat k• IIN'111tKi/n1':1rMI1tICI11~•II MIIIn1Iyu~ttYl.l'.y.tl•IIIIrIN1/tIM.'lh'k'll'fNW\eIIIY'/\I.ItNN4'r:NI 1.111h'1/.{NI.14', IMNnl/lll,' I./ (IIC 111N\/hh' /I/vnivC11M'/N 1./ .//lp'r1.R/.ll' anMNl r:NlN.lt.ln II1C MN4Y.Mh.h la•naMlJ.c rrlalrJ ell..t. l l/c.c IMNVeaMh.h rrr.l.Mlav ImhMr.l IdNYJ Ii.NI. Jllllt•:Ir 1., t\ 1111t•t (C.I L.wafll. IIK' C~IMhIYl.yna(MN' vC.N k' 11M•nltNanC. •/INC tMNI . d1/11n1.uCd /N.///1 .ht l'. Ct(h1yYI N/ hIN.Cf:Mh.h ~a'ru~NIJ.C /ll. MN e><IIIMI a rCIhN InM /n cllhrr IMyl6 .N 1.1w alhNlly ("('1y aullrNlhnlyric x•NI upla{,c. 1•uw a(hnily uplalkc .ul I"l'ly ,n11UN.INnyrN :N Nt JMI I"('INd////1NNV/1M11yfN' aC1/I In1U l'IMIN'aI \IKl'. W:L IN.t alltth•d ,1171't IlNl/h•/INN. In K' 1111•1-ti wnh INN.cf:Nh.h (hY...MIaw' I.Iw at.lnlty NL1.Jr h..W i•r. /• 1.'.lu. r.) hy lip• In/•t. K rN.1 * I4Y' ~II/IIIII•111Nv IIN I/h.11MM IN•.N /a, ul•t.d.- 11 .qq. .r • tlw. t1r r/ hry•1r rN,l Inw •dhNlly uld.dr .N.• dr.1/m 1.uhl .IJlr/rnl t .y.lcnl. w11h the hiy.h al/inily Iran.pNt .y.lcm .trw•turally a.aw c/N•J wills .ynalNlc vC.ICk• nwnlhl.uM•. Ik•Ider. 1: A,•C.•t./N•n, Il., Lahha, A. anll (knnatu• 1 1'.. 11 Nr/ulhlx•ml.by InlrrnJulroal 11421141 151. , 14t17. 11uu1 dM• ('rlNa LN Nrtu.rlM•mi./ry• Itk Nalh:m S Klillr In.hlutr LN 1'.ythlattlt Kr4':Nlh, WcNJ-. LlJlal. Nrw YINA, a/Nl New YINA Unlvrfaly• IA•IaNlnw'nt..1 1(Nd "4y NI('1)IINI INUIII'1 U('IIAN(~IS IN'Illli Atl:"1'AHI)LItiM l)I til'/:('ll l(' IlKA1N 1'K1/11 IN% lIh• t•Itl•l1 rd ,N Wl' arNl tllrtNlK INt/N//N' tNI IIN' IIMIaMdl.ol ..1 .IrY /iN hratn INU1C111. W,/N t'R:11n1nt'.I by nlCa.urlnF' 1/NINIIIN:IIMM1111 IJtICkII vaI1/1C I/NU IN.NCItI • wnll Ik'n.IhMlku/c r/ annlny ld ptulrnl. revdveJ by Ket ckctaMllMNe.i. Acule arNl thronN a.Innni.tralMMlulmt.d/rlClo41UI,'/k/.'IICt N1nlln1/N 21MWr],..1' ,INII 51/11,'rAl!141 41 Illln IIN S tlay. ( A I/v1 Illl/li INN1111 i111t11:Nlll'l1 .u1M'1/t:1M•IIINIy 1) rl'llltt lYI IlM'11fIhN,11 NNI..t 1'Y'/valuK :Nhnln/.lrrrd by ;IpNUnmalt'ly 6 77i lllc re.ult% wtlh CtNtNlll' Il1..N1/N• a1h/11n/.Iq1/NN11rMIH'JIIYI a lal'1k t/I IllkrlltK'e t11t Ihl.l'IICI l UI //NIIIIIIC MI•t-an1yIJ11u/N•, a IINah11NI!JIIrINN11t' a1NJF91111.t, Jllc. 11114111 .cem 1.1 hktt'A the mhIh11NN1 .d INUIrm .ytNIN•.1.. Snlall nNrra.r. in prrMCiu cINNcM were Ilh.ervcd nl a h/rh am/ a tuw nMlk'tvlat wclyht rcltNNl n1 tiUS pnlyx'ryl:anak kel, u.cd ,o .rp;11:/1C ININCIII\ Ifnnl nt•wIMNn INam IN;Mlull twain allCr chHNIN nil•Uline aJminl]uU1Mn1, .C1C.IIvC IINrea4•• a/M1 a Ik•t-ICav' were vYn in Hka•(We harNl.. RC.ul/% afC cIN14Nl:m/ wdll .CICIUvC cllccl% ul nla'INlrlr INI the .yrNhc.iv tN dcgra11a1NN10l .pecilic twaln Ix.NCin. Jrrth.•n, ll . Banay-Sl'hwxq, M., Uunklp,l). S..1)chlcr, l:. A, antl Krnh. M li A NcunKl>,rnN'al Kc4:atch 12/21:1Y7•2t/2, 14117. 1 rlNU the ('t•nlrr /ot Nrunlnccmi.lry, lllc Nathan S. Klirlc In.hhne 1.N 1'.ya hlJorlc Kc.carrh, WuJ'. LIanJ, New Y.Nk. lihUl'.(T O1;AS('OKIIK' A('IhUN'tllli SYNAITOS/)MAI. IIPfAKI'.IN; 1'I/IMI'1", I'111IKN'AMINI:• ANI)1"('1(;AItA Vol• l'IICI't. nt nMYMh/C acid tM the .ynalMnwlmal u1Nal.e ol /'111MI•P', I'111J./ punnnr, anll I"('/(iA11A were cxan/intYl in al.nlplv N/ unJerarrMl the rnelhunl.nl ul Y.I.MhN 1N'/11 NICIWYINM 11/ MI•CI' nrwdn.N /1y 1'1111)r111amirrc uplrkr waN i/N teJ4•.1 at bw.'r kvcl./11111 and 11.1 mM) wNllkcrea.aY1 at hlRtrr kvel. (NI mM) ut .4vwhN• acNl. A.c/Nhlr rciJ inh/h11eJ 1'111M1'1" uln;/ke IK'„ - 11 1 n/M /+uNl ('Y'K ;AIIA uprali< IIC_= NI nlM/ Wa./Nlut lll axlNhir at'Nl re.NlreJ uplake u/ ('ll/Jllplmulc a/Nl /'11/M1M" ,.u1tRc.linR that arcarhic-xNl inllw'eJ lipid peroaiJ.1NN1 w.% rM11 mvnlvcJ in the ef(ect rNl upukc In a.Wlitilln h/ the plom-ihk mwAvemeM Id anliulit Ml.nl nM•, hs n/.nl% in the rn rrl'.r anCnualNN1 u/ the newnluaN'Ny rd MI•11' by A.t'.NhN' at 041. she (Ne.enl re.u1r.11NIMa/c a Jucrl e/ln'1.11 ..clNhir aciJ m Inh/hitlnR Ihe up.kr ul MI'1" /nr11111111Yn/1M'r)'M IM'Ivl' N'1/111n.11\ x x 1119

C.•.J.rn. It : 1k-I.1cr. 1 A atwl l.apha. A h.mnal.d Ncun.\tu-n.c Kc.ratlh 17 2I/K l/ll, I'/X7 IntulllM• ('t•mcr Lw Ncut.ahl'mt\Uy, Ihc Nadun S Kltnl• In.blull• I.K 1'.yllumt ll kl'N•.Irl II, N'•:Ir11 \ W.IINI, N.'w YINII HI IIAVI( /KAI ANI )Itlt x'lll MI('A1. 1•1'1'li(1:C t/1:NI('()11Nli 1N AN MI'll' INlrllt'I II MI111~1 Mt)1N 1.111 1'AKKINS()N'ti 1)1%I'ASI: l ltn\ \ludy c%JtnuK•d tht• cllcc1.1/( nit o/inr.M hV'1RIMMIM Jl'11v/1y a1MI.n111N• h•vl•) NI 1h•II,ut/11M' ( I)A I J/NI 11\ IIN'1•IIM.1111•\ 1•.1 dlhydruR yphl•nylJarlwx td I IK )1•A(' 1; n.l IM•IIMW,It11IIn M nI/1IVA/11t IIN• \IrIJ1Um JINI..II•MI.My Inhl'rlh t.t IIIKI• IIIJI h.M1 IM't•11 la:drd with dw• tw•uart..\ut I nw•Ihyl •t t,lK•nyl 1,!, 1.6 IctrahydaM.ynclnM' (MI'1 i'/ MI'11' aty.mhl.odly 6.wctrd t1N• .p.nlJnclw. Ww/wl.ra.» :Khvdy I 2 wcck\ JtM. r nwmth. J11cr 2 tnN•ltum. u1 MPII' / N1 m1;/1K S(', 24 hr ar.ut/ in ylw,ng :wluh I 1 /IMN11I1\) JMI 4.I11111/l1• (:2 1/ uM•nllt\.ll.l/ IIK• l•IIIYI /tl nt\INI/K• lMl hnINIMNIInI W;1\ hq.6.lal , Jn ttutu,l \InnuIJ11.N1 Ot hI.NIM4.N 1// 1 min alter nw-rNlnc) h.lluwcd I/y a .klwc...ml lt•n.ul IJ\tuty Inwn S t.t 211 mm Jhrr utM•ltntn r..h•rancc lu 11K lklnc\.Jnt fllClt..1 IINtd/1N• 111'v1'Lhtvl J/ICr the 5th.L.y.d d.nly mlcatpwt\al ma•ulnrc 11/ 4 my.Ay S('. Iwn r duly / I.drr.uM t• .bJ rw.l n. t ut thy dJy M 1u 1IK• tnnlal .Imml.ll.wy cllcl I ot mlultnl• A vnulJr rlltlt .d nN.Ntnl' .NI Lnn/1w4.N 3ltlvlly wa. \ccn in mKC /rcalcJ wllh MI'1 I' I la• tl•vl•I..d 011 11'A(' JtaI I I V A in Ihk- InJtunt wcrc tcdwl•d by Jnl.wm/ !Irf In IM•.hnntn tn..4nw' uc.ne.1 •uum•J. IIN• Irvcl. ut 1)1/1'A('• IIA, an111 JA wc/r rednl yd ut Ilw' MI'I I' Ilt'•Ha•11111tp l•, IM.WP\t•1 . Jl u1l• JMI t I/I.Nlll nn allnc dnl 1HM IJUV':111;MIIIIInNWI\I1.1/14l'111/)M•7111t11M'IC\I'1• IIN'It'\I/II\\III,'I;l'\I\Ihalnn-1M1111'h.l\]II IIIIII/Cnl l' M1 I14.MIM4. V.N Ilvlty in MI' l l' Irl•J,1'.) Inn l' JINI th.11 thl\ {•Ill•l I 1\ n1N llw• 1.. .hJn).tiv in 1)A rc.clN,a :n Ihvtly ut the .trt.llum . Ju.cd by chr.uln nalwtnc Nrr.lu'n, ll , I1J\hml, A a/w/ I:qthJ• A I'harat:NldttFy Ihlncenn.try Rc NchavilN ?RI'1 2l1') 1411. 1')K7 I rluu the ('culcr Ilw Ncnnw•IKnuslry, 'Iltc Nalhan S. Kline In\tllule It.t I'\ythiaua• Re.carlh• WuJ'\ 1\/atwl, New YIMk KI•.514)NSL• (N' 111f, /11-V1a•UI'INIi NIi1IR(1MIIS('lIl-AR SYSI'IiM (1F lllli kA 1' It) NI(Y11INVANI) I111: NI'11KOIR1N'I(' IMiIT11W I KA(:M1•.N1 Al' I11/MS114 111 Re.ulls \Iwlw rwo chanye in lwitch lK Ietanic nmlracliam amplilwk hetween la within the ynMq.s tc.1r.1 N.t nicrMine tw M'l ll/MSH 4 NI InlhkeJ chanpes l, cuneJ in c/lher p.\I re.t t•r ry.\I tc•tania• Irncntuatam Nu Jd/crences were secn in mu\rlr wet wc/KM. I'up. IucaleJ wtdt ntaAme during prenatal and p.analal Ide as t•nnq.arcd /u cuntul4 ammal. l\attm -saltnc) \MwrcA \MMCr Iwltch claaraclirxt dunhunc irwliraltng a Iroae rap/d twn.h 1•tcnat..l A('lI1rMS1/ 4 111ucateJ pupa hall MMnewhat Ntngcr Iw.l.h w.tt, nn.w.rw 1.,.1n.d.dty lu Iwtp\ trc•nc.1 with 65100 7831 i r- candy la\tcr Iwitl h hall rclaratinn /intc than pultv re.-eivtng niclNlnc pt\tnatJlly lmly 1'uln IrcalrJ wrlh n1a.NUtc durnnK prenata) and ppMn•alal lilc a\ C1N111t:IR•II Ill IINIItuI anunal\ .IwtwcJ ;In IrM7l•a\C in Ietan/C l•tMMral'IMM tluralNM t/MIN'JIIIII! Jn lnywuvcJ Jl.rhtv In \a\l.uu Ictanu\ ( Illyainp rcccrvinp nicrdinc prc anJ Irntn.ually h wl .IKnth r:wllv WatrY•r IclJntr c.mlrarlNn111mes Ihao /hlr\e Itlrp% rca'crvlnF onlNUk (w..lnatJlly IN/1y Adldl I'UI. mu.ck, nlak up rd prty4mtinaMly la\I /vl+e 1/1.cr\, tmtUally hJ\, dlamy /MMIIIai lkvchtlomcnt, cnrNracuk I+ararnck•rs \mnlJr lu tlwr.c u1 \h.w typl• hlrt. Na tNur• ncty cwt clctalc thl% maluraem pnw•cs>, whtk A(' 1 t I/MSI I d III otJy hevc ht11c cllcrl J\ vcn Iwo wcch\ altcr hlrth. K I aal SnnnJ, f'. l.. ~ AnnJl.l.l Ihc New Y.n). Acatkvny tt/ Sa•icrk•es 41W:11'/ 122, May 27. 14//7 1'Hn/l the IIN.L.yy Ikp:utn.•n/, Ncw Yluk Iloivcrsily, Ncw Y/wh V. Pharmacology, Biochemistry and C ell Biology kI:V1:RS1111 F. SL()W• ll/illr-IIINI)IN(; INIIIIIffl(/N (/1• IIIIMAN 111 IKI K'Y 11: ITAS'fASI: ('hi AIJ Ala /'rmarnlwnVal Ch, was syn(hcsiicJ 'fhe clmqrNmJ mhlhn\ hu man M•w'lr•ylc ela.lasc with K. =( 11 x N1' M. 'Ibi% rdlihul» i% a reverslhf,•, sl.tw• ughl Mwhng /otuMlNlr wnh A_ = 2 x N)' M' .' k- - I 9 x N1 • s', FIK Ihc Mt1uh11rv:ItMN/ l.I c1J\un by I lI.f. by 1 t(' .= 1N/ nM. 'Iha rnhibihw ia lhc nrt.l cllee tpvc akkhylk lu kC11MN tnluhtaa ut J.crnk palcurase yet Je.erihrll. 1lurdap• R 1' . SllwK', P I and AM•lr., R. U. NNtlhl•Iml'JI arMl IlM.phy\Il'aI I(e%eart-h CtMIMMMII'aNNMm 14S(1)1, May "), N)K7. hr/wn Itw 1)cp;/nnK•nt nl anKhcntistry. Il,tah.n Ilorvct.uy Sclurtl td Mcdwtnl•. Jtwl (ir:duJlc IkpartnN•nl ol ttMw~hcmislry, (lranikis (Imvcr.uly• WJltham, MA I:X71'N111:11 IIINI)INt7 IN/tlhlll)kS 111: l'l1YMl)1RY1'SIN 'I IIA UIN I I.KAt'1 WII I/ I IcAVIN(i (iktK/1' 5(IIISII'1:% S,' S; Wc have \ynlhc.i/eJ inluhiaw\ ut chynw.lrypsin, ha\eJ un /lwKlwlcdlyl kclunl•\• that hinJ at S and S' whsiles. "Slnall" inhihilun n/ aerine Iw.Ncases• whNh have previnosly been \yrahc\veJ, rwlly inlerar/ with S wh.ites. llle parenl clMqxwlnJ 1\ Ae-leu-utn/nt t'he ('I• 1t /1) (K, = 25 x N1• M/. llris inhrhihw was nwMldw'd by sw•ce\\rvely replJclnK 11 td the -(T,11 Rmup by -('11,('H,('ONII('ll, (41, ('ll• ('ll.('()NlI It'u N11Mc (S). (l1,(l1l'()NII (tu Val(11:.1 /61, .al ('11('11 41

1 ( Y/NI I( a•u Aq• I IMc• 171 ('.Kre.INNIJIny A, v:dut•.:uC 7 K/II.11 21101, tl 21(61. •uNI o 111.1 171 pM I alru.l/ng 5111 6 by .Nklltnm al V•d (11 t al 1'.' .kr•. INN tka rra4• A, lu t.Nlfl.l.l, C711c'ua.Nl ..1 5- t.. 7 hv uKININNdImI! AtI,' (IMC JI 1': .IIYrCJ4'. A. JI.INIqI nl.ltrlv 15 Iuld. .Npl•r.unl IotrraclnNl hl•twcrn Arp rn11 Ihc S.' .nb.Nc INII INt...r/t• \INNNI/III! /ulfl•Nh.N/ •It 11LN .uh.It1• with V,11 ItIC.C rC.utl% art• In:MY1KJ.Una' Mllh Il•41I1. IIIM.//1N'll w11I1 IIN' INNIM.k/~.N1. /•//IIIIy nl :IVI•In 11V/NIIIN.NJ IIII/J IkN11.11/1 (Nn Il'nl. 1't.Nfnl. wilh A/F .11 dN• I',' IN.vtnlrl.hllw ht}hly IJvIK.lhlr mlrr:Il InNI. wId111N• IN.dr.14• .11 tll.' \.' .nlb.Nr I IN .c tr.uh. r.tahb.h Ihal nk IKINN:Iu.NI ul rt.nhn. wlut b mk•r.Nl w/lh \• .IJ+.III•. 41'/nhl.lntly nNhJV'% thC c1hl:Ny Id nlh/hu1N. au11 thal v1I11.1hk' IIILNNI:IInNI tINNt'/111111! 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S K. anlt /'..G/4. / A( . Nrur..,c/en.•e 1W'1 M11 627. 191116 ()ther upNNt ('anlcr Ke.carch Cam(+a/Kn I rlNn 11k Ik•partlnenl% ul Ih.nlchemiary anll MeJicine• Kuyal /'n.1gnNluate Mel'iral `11N111I, I /NNkN1, I' nF IJIN) 65100 7849 1 I111 I KI 1• KM)I('AI. ('IIPMISIKY (If (•1(;AK1:7•IT SMIIKIi ANI) I IIIi INAI'I1VAIlt)N(/1 ALPIIA 11'KO"Ili1NASliINIllItll(1K ('/y.ucne .nw.kc clo he .cparalcJ IMI/ ra% phase .nwlkc alrl blr. :uw/1NNl1 phav. a.NN./•n vcry 1u1•h l INNrnn.Nnwl. 411 In•c r:wlical. 'I:It caxNam..l:lhk t:Nhcal, that a./n It• .d...•rved J/ra•l lly I.y rkrllr.wl .pln re.+lnalK-l: 11:SK1 (;a% ph./.c .nM/kc cl•INam. N'.MIIVeI':11ItNl alwlutyl:en-.cnlrlrJr:wha•a1.Ih:Ncan/wNIk/lhvtvcJJua•cllyhyl.~K INN cau Lr Ilh.crvcd u./nF tlk 1•tiK yxn-lrap nr•Ihlwl. I IK I,a /,whl.d 1. 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Itra• IlP Irur:Md. ('hr.r \IMIIC\ IMINaIe 111.11 hl•IIN.II.lpyrenr a1n'1 cl*/udc olay MII he Ihr III./IIM Ilh•17h„hlt ul 111' mvutvrll in pl..hm huwlml;. Wallm, 11 ,)rlltr, A M aMl Grnrrlfa, R M. (•arx•rr 1x11rr. IS 114 1•1h, 1'/117. 1 nMn Ihr ('anccr t•cntcr/ln\lulue I.f (':•nrrt Kc.carch, (•Idumhia llnrvcr.ity, New Ylnll. S AI)I:NIriYI. 1. MliII111)NINI: MI'1)fAll 1) PN/.YMAI1(• MIiIIIYI.A111)NS IN 1111• 1'1 A%MA MI MIIKANI•S ut• 1111-. III/MAN IK111•I1l)HLASI' lo ttvcnl yr:u., .evrral eniytn:mr rcxlNlnm mcalralrJ by S alk•me.yl lL nw•Ihulnun• (SAM) havc hcrn,k\crllx•.I //1 thc\e. Ial \lepwlv c,.nvet.M•n ul nlcnl M.IM 1•IM..MI..hdyk therndaminr 11•1' / u. ph••.phwtrllyl N nlclhyktharllllanrok 11'MI• / ll'1 Ihvldn•y•lldqa•1N 1\M'thylt1.1/1IC1.IM'\II'Mf (aM1111•/tb1 /1'1 AU I I.v 1•..A. ul , atlr.. yuw'IhvL,.r 11'., \1 . .../ ..... n. . . . ...1 . ... .. / .... .. ..I. /•, 1 .n. a ..1....L.., lu. 11.~ L..r. 11•A(•MI have rra•rlveal c,m\iJrrahle allcotnln 1r•cause they have hren intphcatcd in vvrral crllular /unrtnat\ aMl in hin\ignal tran\ler aanl\\ rncmMana•. Inhlhm,m lul SAM nlcdlaltll rniynK• rcacti/m\ in iMact human placcmal vr11om ha\ lkprr..a•ll 1hr .i, uvr ulNakr ld all+ha-arnlMaiadwlyria• acnl/AlII1 by thi% li\.ue. AnuM, aan) ulNalc \y\trm. arc kM.wn la hr kKalvcJ in Ihe pla\nla mcmhranc. lhcrrhucI thr p1a\nwl nlcmhranr ul tlr• hutnan Ir111+IwIMa.1 wa% prrp:urJ and SAM-nKJlatcJ nwthylau,.n\ wrtr \nIJIrJ t.o a•valualr a. 141 whlah nne 401 Ihe ahuvr rniyarc% mIy111 play a adr tu da•Ixr\\rnF 11k Allt upt:dc. 1hc pla\Ina nk•mhranc ad the huntan lull lrrm placenlal villu% wa\ prcpartJ by ral.d1a11un ul mn'ruvdll Inlm.yncyliMnK+lwllda.l aMl lldlcrcnhal cenlrilugatnm AI {,al•Iw• I,lu.y,hata.r aMl S'.nuckMlJa.c atr markcr rniynko faK plarcnlal•\url:lcc uw ud+rarr•. 11M u:Lirvtllr. wttr rnricheJ hy ahlwl 2t lukl in /he pla.ma nrvnlwaM a. a1Nlry,•nrJ tn 1hr vdlu% h.wtr.genalc- The pla.una memhranc Clnl/atlKll clVylllr .y\ICnI. whl. h IlnoK•J 1'M1:11'MT 1: K_ 4•. µM, p11 rM+llnwm 8.G/ anJ 1'( • 1I'M 1 11 K_ •_11 tl M, p111hHmnun 11/ 5) PM'1' 1 wa. enrw'hcd nl lhe pla.rm menthranc I'art /.1 tIk• I'Ml' II /ah,w14/PR I wa\.IduhlliicJ and pr.\/hly krN JurinF Ihc Incparalnln.d dk plr\nla uk•nlManc Iivcn thrn, 1'M'1' II wa. al.wl 4thmc. NaN ol 1'M 1 I fhr aa uvna•. ul 1'l •M .uw/ l Al'M wrrc con.iJrrahly ktwa•r in the lda\nla mclnhranr Ihan IM/\c in Iha• vllln\ IMn/N,/!rn,/lr I hr\r /nvrVl/,'WNIII\ NI~`~•r\I (hal hli\/IUI IIKlnhfaM• 111M1\I1IN/II/N.I N nM•thylatnnt rlay% a\Ignlli.'nw nde In Ihr u1+lake uf anuM/ aa'al. by Ihr hllnl./n tnlrlnA.L.\t Tran.n•n/ x'cunudalwln ld 1'MI: in Ihc mcnlhranc Irpal Inlayer Juwmg plw.ydulllpnl N nw drylatnnl lnay aher mrulhranc QuiJdy whwfi, in lurn, m1lurMr\ Ihc lalrral nucnrlt\plracmcM aMl alirnmenl ul annMe acaf canln .yarm\ in thr IM•m hranr aMl thco tnlrr-•Linln% with amiMt ac/J.. Ilanlwcll. S 1.L aMl Sa,nv. B V R. Tn.llhlllda.t R/:.car.h 2:YS•120, 14117. (Nha•t \ul.ltlnt 11 S Public Ilcallh Servia•c and 1'hamtaa'eulical Manulaclurcr. A\\.r'1- al u MI I'1 nl l klat 1,1/1. I I•nnll the I)r11:n1/11l•M ol 1'hannanrklogy. VanJcrMlt llniver\Ily tich,r,l 411 MrJl.irr, Na\hvllk, '/ N Rf.CI/)NA1. ANI)11IfFI: .KkNT1A1• SIiNSIl1VITY (N' (IMNILI('(/1'I.AI•I:NfAI. 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S 11'1', mcdlnt, aM/ clhyl ak•nM+/11i1/)111 rn Ktrh% hicarlrwlaNr hullrt Ip11 7 4. 17••(•1 In Iht•.r prrparab,nt\, /n.rra.rll va\culm ra•.r•tanrc 1\ /Mha'ateal by /M'ra'a\CII /l•n\MM1 1M 111n1L:N1nM1 u1 II1t va.rul•n \Irql\ Ilw•.a• e.ltnnterqa gave Ihc lulk/wlng tc\uh.: IcU S/11 wa\ vrry IMllenl hn a'a1/Vn4• l/nNral InM\ nI un11nINJI, th111nMK, aMl villu..Itm 1U(•., N•1, 47. aM11t11 nM, ta•./t•a tlvrly / arrrua) anlra; (h) nKalhnc IMkKrl) aYMNraI'INM\ m u111h1I/a /I, chlni/lnic and vdlu..lcm artcrial Nrillc (li('., 2.4, ). ~, anJ 2.1 mM, rc.lta uvrly /. a 1 1if/)11//1 S Itu 2 IMX•, v/v) h:MI111/1QRM1aI ellerh.Ml WIIINhI'aI ant/ rIMMp/11N' a/ter/aI .rrnK M. 1/% e/lca•t /m umhth.vl arltria) .trip\ wa, mmimal runlra.1nln.ln Ilal cldny ` I11' wa\ k\e rl/rrlrvr ut 11K umlwln'aI arlen:d .Irip. Incuralca/ with 1:11111 Atr•In I 111 1 .• /

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A chN1eJ I1 M1-Ma.e pa/r (raKott•rn ol nww.e rrlN•u livr 1)NA /pl•1 11/ wr% u.cJ >t% a pr/d+e in S.wthern hM/11inK ealN'rrmcnl. M,NIV• y,lcrn atwl 1.12111 Iynq,fNNnu 1)NA N+I+rareP ub hc rNxmally methylatrd aN Il/r/ll .nc. pa,hrd hy Ih/. v.tlN rN c Pr 1erNt rrythn.kukrmia crll, aml Sp2 crll l)NA MNh .howrd an rMwNtu:d halNlu,y paurrn in ll1w111 J,Kc.1. IlytNwhiNN,n rn vtu h- NN•faph,lw• l'MMINNtNIM~ %tw,Wr,I I/Iat 1N.dN•d.ey1N•IN r% werr M.,ally rmer.IN•rad ahnq' dle arn,. 1 1S

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Ir-r..l llmn«N/:dlnr. 110.01 /w•Innt aml Irthafw "ire dll/crrnllal I)NA uN•Ihyl.Itu1N1 101 r.1:d~h.IN d t rll IlrN ;q•r. Ildlr•rp, M I' , I'1/1N11'IINIII, ti I, Kb.ak, I JMI .Snlr/b, J.S IIN' IINIIII•II Id Nndlq'L.d ('hrnu.lry Z6:1:11 11167 111716. Aul•u•1 IS• 1'/N7 / NIN•r %NIMMNt N,I11.N1.1) In.lnulr% ul /lcahh I r/N111IK I)IV1%N«I, /1I SIIlprry :IrNI IINdl.yy, ('Iry l-i Ihyu NatNm.d MrdN'aI ('rNtrr, 1111.Ntr, ('A. ,NNI Ih•p.ulnr'nl nl I'rJljlnl., Ilnlvcr.ny Ill Cal/hNnr•1 al I.... AnFrlr., %l IN.-11it Ml IIN I/N' 1111MAN 1)NA I('YIII%INI SIMI IIIYI IRANCI I KASf %I I.1'("flVl'.I.Y MI'IIIYI.A11'S 1)111'11 X I>NA ('t/NIAININGMISI'AIIt\ IM INl•.r/Nr /11 Ihr (''(' 1n1.p.ur ul .1 J.'blN•d duplrs ullp.A-./tvltlNh'.NNk t'r. h,Na'rlI ItN1.111•N /ly tl.N'/ vic e../ •Ilh.n,dc IIN hlyhly INUdIrJ hwu•In 1/NA nN•dlylu•ul. It'I.IM• AI1:IIv,1% l/I Irlll,la'1I Il'.N 1/1N1 INlAI1N 1% 'IN-wrII 111,11 Ilse ('1 1111\h,llt :N IrI) .11 :1 uNlhyl.Inlm:Nlr/+1,N" In 111,11 it w:1. n.r/l r.1plJly IIIrlhylatrJ Ilse mY'•(7 ha.c p:nr ala/ rn1/.NN rd the 1:111,N /ly 0.1 Ilse 11I1F1«Il'11tynIN IrIMNk 11/ V•IV1' a\ a Wh%lr.nr IIN Ilse rIVV/1N• 11uMrvi•r. Ihl. ~uloplrNlrm:uy h.IN• Il,ln wa. hNnNl Iu:N1 a% a"U/rihyl:ll/. n 111tr111N ' I hit 1%, Ilse INl'N'/N r UI Ilse /11 C/n INIr Strami nN11N rd Ilse rmynNr 111 r:lpldly nN•Ihy1.11r cN Ilse cyNNnN• tcadur lm Ilse I~I+INI.dr •Ita1N) in an :NI/,N l'll) (''( i h]K 11,nr Snudl. S 1, Itardy, I' A:mrl Nakct, I/ 1 Nul Icll Al NI. Kr.rarrh IS1171 blllrr blrl(., 1'qS7 I/1IN't mIIyNNI Nr1nNl.d In.plulr. ul Ih':dlh ( ruln 111r I)v1.NN1 ul SIrrycry, ('ity ul 111hr N:nNNlal MrJaal ('rnlcr, I)uatlr, ('A '1 A1' AN'I I(:1'N 1(1KM1 1)1SI11.1•II)/? 1-INKI-I) HOMOt)IMY.Rti Inlrrkuk/n 2111 21 i. rr•fNlmlhk (IN .tmlulalinR T•ccll pndilcratinn via mlcr:N - INN/ wlrh./t•t dn . InFh alhn/ty menllxarlc rrrr p111r. AIIINwyh an 11. 2 binding pmll•rn he.IN•rn Nw•IdlhrJ by vlrturr ot qc tc:N'nvny with a rrNNNlchNlsl annMNly Iha1 rlNnpele. w1111 11 2 liN hu«hn/t L/nl/ 1•N /, Ihr tlmqplrlr :/nll (NCl Ilc %rnN Illrr nl IIIININNILI II. 2 /'., rlw~.l. 1. Iltl Nnlnnwu I .. '11'II/N' II//lIN'1 IIN• 1 uln/«1\IINNI --1 11 .2/r1-rfNIN\, IYN/I 11. 2 il.rlt anll and l,N- wcre u.cd av IigarNl.l,u adaxh uK InlNaoe pnMrm. IlN analyvl% hywiahunllhNkcyl.ull.llc/pdycN'rylanlilk Krlrk.1alptNNr.1.IN:d1.Nlti(!,/1'Al~l'1 A vculrly ol ra/.•rtnN•nlal allhnl:l.hrv yahl tr.Nll% imlw•:Nmg Uu111N: l x antlyrn, wln. Is nuKr.n.•. 1../ .ulylr prolrm nn NalANISl1,/PA(il: ulafl7 IIYIuI'1/1r. l'lNNI/1NNN, 1% almo r1tNl'\Y'lI J% II1%11II11k linked INNINIIhnll•r\ :nNI 1/11l!4N111'r\ I-.It:IrnIrN.YI urllkr rNNnrlI1N IIIF /111NI/1aN1%, INNII :a'tlv:Nrll INIr11t:lI hnllldn I ccll% rtaf.rll IirN-./nnn pallrnt, wllh :NI1d1 1 1 rl/ knka•nua l11( I I 1112, M 1• 11 r.prc..'I:N' anhprn INNINrhnlcn IM• HIS INNII in ,11kI/1NN1 a111NNNNnI't% IA/, 54 (NMI) I'1N/11a/NN1//1 Ilse /h\Nllak IMNMI 1\ M/t a l1NIV qlN /Nr ul 11N' cRlt•1nIN olal pnrrdurc% uvd w Lldalr Ihr pr.Arin% lllr an3lva•• rn.l. IIIINh :/% NI1911N:1i rr%uttN are uM,urN•d when t1N• rcccpNw pnNCmc arc rlrhnalyd rnl t'AIrdl h'lI /11 Ilse IMryMl' Uf N l•1I/yI/14t1'InlN/r IN 11r1•pire1l IIK ckCtto111NNCV% 1/1 (/N' :/hN'IN'l' ul IN':N /ll'1IJ111rdINN/ ACl'/KII1111[Iy, IIa'H• /1/NI//1~\ f11NM IU I-al' anh);l•n a..." / L/lnl/7 wIlI1 11N'It /N('hYl'nINIIy I hl' 11hy\Mlhl~a' NI!n1IN'JrN l' I/I INN/NNI//11rr :/MI uhl'll IIN•/11N//1.IIN//1, r%INY1JIty :1\ 11 tl'IJtI•\ IIIt1a• IIN111:11aN1 UI h/l!halhnlly II.- 2 Il'l'l't/11N~, 1\ /Nl'V'lllly 111/klN/wn K:IIa, K J/NI .Smnlr, K. A ISar IN•uN.uy 2h 161 54 51trJ• 1487. ( MIN•r .u/MNN1 NalNlrlal ('a1N'rr In.lllulc aml 1:11 Lilly ('arplNata.n 1'rlNn Ilse (k•punnN•M ul McdlrNlr, I):Irt11NN/111 Ml'IIIr:1I til INNIl, IIAn11vl'r, NII '1111i IN17:K1.I:IIKIN 2 KI?Clil?(N(-• /(/N('I'K)NM. (Y/NSI•.U(11'N('IiS O1• 11 X 111M(1I .L('ULAK S"hKI/('l ( IKI: Ihgh allinny 11.•2-R binding re.ult. /ral/n an excclMwmal lypr uf llNll+l•rallvr inlrraclNln between 1wu 11•-2 hialmK pr111cm. Icmrcd a aml /t. When cq+rr..cd NI rrlhrr nn the rcll .utlarc, lhcv 1wn diNinlt chainm hwm a tauw'uv•rkni kirk tUC hyM/d nYY'IM/N l'IN1111kR Ihal etp11Nh a ra1Nd aMMN'Ia1N111 tAle l'/N11t11Wtell by Ihl' Il« (t l haln arNl a.f,lw .11..11.•ualilwl rale rharalkri.IN' hK tllr p75 ii chain '1-hr 1,75 n chanl../Fnal c.•11 Kn.wlh, w/N'nv.Ihr pSS I1 chain.INl/y Iacdllalr t) ••2 binding by .crv/ng a% hcll«•r hlrNlmK .nr.. havrmy rN/ di.crrnihk.iFnalink tuk Ihrmvlvca. '11N• umquc IwN d.Nlal InlqdiralilNl. r/l Ih/..IrlNtural lK~,'arIVa1NN1 irNlic:NC that Ih/% c1N111rranvr hulN/h•a'uI.N anankcnN•M n•/kl t% a yrra'ral nlrt hant.m by which 11N• c/b, w•m•y ul •lnrlacr trcrlw.Nt can la cnh.nNrd matkl•Jly Wang. 11.-M. a1N/ Smnh, K. A )oumal o( l:yrrinN•ntal Medicine 1(16.NISS N/hV, (khlhrr 19117 (Ahrr .IIMNNt. Nalalnal ('anCrt In%l/lulc a1NI I'.II LIIIy CINIMMa1NH1 Fmnl lhr Ikpannlrnl l-1 MrdNinc, 1)arlnNNllh MrJrcal S.'hlNd, /IatNlvcr, NII 117 I Ih 65100 7854

IN I I N1.1 IIKIN ' IAIMIINI MSSA1' USIN( *.MON(K'I t)NAI. AN ItHOI)11-.S I1.11.',It•//.l ,l'1•V11v1' .11NI tl'(NIRIt/l Ihla' 111 / / 11111N.a,\Jy I1N Intrth'l/{.111 2 (II !). 1w.. II ' Il'•N 1IVl' I/NNNR LNLII Jn111b11I1C\ 11)M< I JtNI l)MS 51 wrrr c11.Ir.Rtrrvr.l l•al: n ./.. Iv (1N• nn1y1R 11 .` huNI/nF t hJr.N Irll,lN +u1 I)M\ I atNt I )MS S wrr.• r.Id.NtrJ I.1 I..n./nN t..n 11 '/.nnIN/N.J...ly th•n 1, a•n,ll/vr tn 11111M n/unlN a/Nl hllllt:nt 11 ? t 1SIt Iq•/u111, :InR a.d•Ir I..IhNh r.Nhul..d.hNl JINIrII/yln.ttlC Ih•IeltµN1• 111N11C,NIIIy •1v./1L1Itll• t...N1h'1 Ldh•/eb.nr% flud.l. K C .mJ \nrrlh A A Ilw/ lr.hn.d.q•y J'/NI 'tRr,, N..vrn/hrt 14Rh. ()IIN•1 aqy.Nt N,Ih..n.d ('./rlll•t IILUtulr atNi I:II I,/IIy ('IN)RN:Ih.111 I l..m tlN• I i. p.utuN•nt .d MrJn /nr• I t•nulNNUh McJIt Jl 1/ Mh.l, IIa/R.vrr, NI I IN11'R1 I t1KIN ! AtuN(K'I t)NAI ANIIH()I)Y AI•fINIIY AI)%ORI'11()N 1111 I/(1IIl AI HlH 1(11 111N1)IN(;KINI 1I('S 1()K I)1'IIMAI. IMAt11N/)AI )SI )KI'1 II IN Wlth t1N• rC:Nly Jv.ldahllny ul nhNNR LNI,d Jn11h.NhC% rCJ.tlvl• with an Ca1l'mivC .I.ra 11/11111.1 .Inrt/•P/l.. /II/111urN1.111m/1y .Nhn11NµM ILIV lR'l ININ' IINNC w11h'Iy ./11~.111 Jl./r lIN IN1.1.In pur/hl.A/.N/ IL.wrvlr, 1'/vl'11 4'VI /dI IINNNR LNIA1 JIIIIhIRIM, rl':Iltivr wlth IIN' .:n1N• .Inu/•cn. an..t Invc•U{•.dar. ILLr I.•und 111.11 ..n1v a Icw aat1MRIN•. ue uvlul I.N ,UINI I.IIJw• nnvuun.elh191v .1/11J/•. n I.n/dh .111..n n...N.hn/•Iy, lo nllkl II..Ic•1.'/ IIIIIN' IIN' ~..11.11/N't.'/,..I /1h.n.R LNLII.1111./w.I~ .11111r•111h11hI1n/• I1N.,1 IIII/rN1.11111.N l'Itl't Ilva uomutN.,llhluly J.L.NIMUm. r.1111I111/111//1 .11N/ L/IN IN h/rIJInF .'.IR'r111N nh w. /l• IN•1/.NUN•A u.nly //NhnL/t.IrJ unetl. u\nl ` ill '1 •/. .Inlq•rn .uR1 L.ut .h11. Irn1 II ` Ie.NUvr uwNNNhmal :In111RRhr. IIN' .11111Ih~lµ, wt•/1• LNI/NI 1.1 ddlr/ I.nnl,ody wuh Ir•IR•tl la tlMn I.ItN•ul 1.11NI111C llwr,µti•rNtN,-.It 1r'l11 ' IRNIINI W two ul IIN'V' a11111NN1NV vrry 1.qN.lly, wlnlr It I1NN11N11U IIN• .dIN•r 1wu nNNr .hlwly WIN•n h/rNlmy w.l. Iw r11NnR d al •1 ( '• thr l'aI111I1M111/11 1I/,MR 1•/111N1 CINNIant\ hy a1I t11 1IR' :In11hIRI/lY Ikt rrJN'lt Ihlr 141 a nµwr ItlirAt•tl fMal/Mlg:111/NI I.t thC /Ii..IRiatllNl ratr Ih•m the :KMwIa luNl ratr IhIwCvCr, JI •I"(' Ihe a\MR'IJInM1 tall'\ UI the Iw1/ %hlw-reaChve :In11IRNIµ'% IRV anK rraulkd +11 nl ukrdly dlal rllN /rM alhmty aJ./1qN11n1 JIJ nIw Ilcrut Ity com pJnwNl. 14m h11th Id Iht•.r anllhlrhr., elliclrnl rrnwwal uf II. 2 clndJ hr 11hl:utK•d 11 :µI,.N).Ulnl w:1, IR tIIMIIN'1I a1 A7'(', I1Hw/Ik/I IIK 11 11 1 / 111n Ilow rJle wa, all/n,IlY1 :IlY1N 11 . Inf' t1111N• 11 2 a..IR/anlm rate K/rtl•t7a t/N1.NkraNIN1% aL11dn-1a/CJ 11.2 all.urhtluNl tll /111\I//rC, II Iw111N IIFNI' nMNNt 111n.11 atltlhlNhr\ II. 2 IIIIIIIII/MI:NIMNIMNM cINrI'I•nr1l wlth 1111' d„IR ta1N111 1.11t'% Id the irNlrvidu.d an/1fRRIN•.. ta/lN•r th.ln Ihr cyu11/fNlanl huNlluy..N/.la1N. Ihr.r tr.uh. IrNINJlr Ih.11/tN' /1N1\I I/IIlRN6m1 pwJnlacl I.N a•1 hIN•nt .dbmly :NI,INI111.N1 1% thr a.,ml•IINN/ rJle tINNt7n1 lit A111N111N1, the /1•,ult. I.1N,nIKQ IINIn.1/C Ihal nNNwRI1NL11 JrIt/1RRNr% may ddlcr m:IrACJIy a. /rI;J/J. Ihelr &nN•1/t hutabnF .hJIJ. N•n.iN., and thal atl jnu1NRllr% ran .rrvr a^ e11rc11vc nn/11u' na.NlaNhrnt., IN..vNkd their anlirrn MrRImF ahrrxleri.Nc% atr Lrnlwn I1u.61• K l JIN1 1.na//- K A Lnun.11 d InulNmnl../•h ..1 MI'Ih.RhW. ) 17 ?dN. 1'//16 1 ( hIN•r ursfNNI Na1nIn:11 ('arN•rt Inahulr anl) Y.11 Lilly ('INplwatlon. I r.Nn thl• Ih•p:uulKnl of MrJla'irlr, 1)annNlulh Mrdlaal tiaiNN+l, IIJINIvrr, NII RI.VI RSIHII IlY l)F GI 1 ti(N.IN/A('1IN IN'II:KA('Il/)N IN MA('kl /l'l1AC1•S- IiVll)1•N('li /)f ('a" 1)1'.1'IiNI/1iNT ANI) ('a ' INUI1'1'.NI)1:N1• 1'A-111WAYS R:IpiJ :nNl rrvrr.ihk a.vcmbly /If an arlin m.11t/t in the Itripllrral cyluplaan 1% a.w-c1:u1•J with the nN+11k lunt•/i/w1% ul m•rulmahan phar/acylr.l/) AIdNN/yh.cn.un a)qNn.1. I1rIR1111 r a Iran.Irn1 rl,r m Ihr mlralYllular ('a" c/1nCro/ra111N1 whNIl (Mr1 rlk. 1IN' IN14•1 III k11111R'ytl' at'Iin a„Cn/t1ly a1Ml nNN/hly, it /\ aIN1 :yhlarrnl IhJI Iru1,IR yie :N 1111 a\N•111t.Iy a1N/ a\MN'/all'II IIN/venlrnt\ aan JIVI Ia1lC Illal'e /11 MNIN l':IV'\ wllh.µn a Ikll•1 t.lhk I/N tt'aM• m(1M l'y1./411N' ('a ' k vrl '1 hrrel/we, hr.uk. ('a" , an •whhtNNl.II .11'/L11 1. nnPlN:nral (1M the Iegula1NM UI at1Un a.vnlhly a%Mll'/alelf with ku1.R-ylr nNNlhty ( i.Iw11u1. a('a" -Mrwlmg prdr/n a/ nl:aumahan ku4.N ytr. ar11111thrr ce11,./. a INIh'lll IINNIula11N /It at'tln hlanll'nt kngth arnl 1,'rI:ItN111. In t111• rreKM'C 11l tllN'tIN/N11J1 ('a ' t'INµ•rnlraluln, INndICJ LYIv111n1 kvrm al'tln h1anICM. and rCn1a/M hlNnll) 111 tw11 .l.lm uwwNNllrr. at Iln laa(,'nlwin~,' ct1111111hC .evrrell IflanlCntc whrre /1 h/11a1% hutlN•r exlllanKe /•1 /INNNNnrrm a11hr end 11 the.e e11e.Y% were revrr+lhk. Kr1.l.lln a1Nd11• in a1NNrr1 wdh dhrr actin-Alnlhnp IlnNc/m, reFulalc the a/:Nr ul INdynu'niatuN1/1/ arun /n re-,IRNI,e 111 than/[e\ in Ihe Cy/11M1111' ('a" cunceMralilln 1luwevrr• whl•rca. Iln INrNhnK u/ purillcd Kckr/1/n N/ alain i% hiKh/y ('a" •drpctNknl. n 1. /Nlly partlrlly ra'vcrvJ in vrr..n hy a M/werinF n/ Ihe calcium cllrN•eMratutn 'Ille •r.Mhtilln ul Ille a'ak lulll chrlaNlt 1:(:TA t/1 the 2:1 al'Im/ ,I'eIM111n CIIf1411CR IIrr/Nlt\ IMly tN1e 111 t111• Iw11 hlNlnl/ al'lIM 11/11mcq'lales rewhinR in a 1:1 wUn/grlwllin ctNllpk>< which I% inrarahk /d .evennl; artin IilanlerN% even thllulth the c/lml+ku can hhu'A the la.t Kruw/ng end ul at hn Idrnk IN% II aMNhef I/KChani<m, tMll tllrlYYly /nvtllvlnl,' l'hanl,'C% in ('a" l'lltnYn- tratnln, wa% ahk III IIi.f11Ci71e the 1:(if A-re,4.lant xlin/~,'cl..dln clm/(111•t, q w/luhl .uyKr.t that Rr1.111in has a rrMral n11e a% a regulahlr ol Ihr aclin maulm rn 1•nv1 ('halNlnnirr, l' , Yin. It. 1.L anl/ Sar.vel, I'. I'. hlurnal ul I:.III•rinlenlal Medieinr 1hS:97-hlb, lanuaty 191(7. t Ahrr suplN.n N:dilNlal Inaitulec of Ikahh. 1•nMn the Ilrn1au1111ky (Mn111/ry IInN, Ma.aa1-hu.etl. 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('Illkcbvcly, thr.e rc.ultaklnlln.lrate Ihc exi.ICac t/l a rcy.ul.lalry Iw•Iw11tk cluna.llmg Ihc l•ilflrc\\NNI t)t Cllt•1111V1' lunwlr iulnwnNy Our fr.ulh tknwal %h.llc Ih:N 4'ICl II.NI Ut hIn1I111l! 31(e•rt•Ialtyl W /llay IMII he a\II,'nliN•ant t•fllt'rIJ ItN (ln' tk•vckqa/u•m Id :In nlNqyrc vaccine. A Itltcr n/rk•r.larwlinp td Ihe rcKulauwy Intcl..< INNh IIMhhtYl by an/l IIINMyhe% is Ile{Yklf I/N the tk\II,'n tlt t•I/lY't/vt' a11111u11NN I/III//tlnlNhl'1 d11y . Kryth.nN/llurl, S, Sal•ki. Y•(lwn, 1 1• Inhc• il., Fuji, 11.• and A..hl.-r• ll Itw• /ouln.d Id Iuullu/Ntlugy 11'N11 271 1)R, luly 1, 1487. t N1N•r %I/I.It1Nt AtIN'flt'a// ('anlt•r ti1qll•ly :nMI (l1C N:AMM7I ('ant•cr Inaltutc 1-tunl tlw• Iklwrtnrol nl Mnkculx Imulua/k.yy. Ka.wcll Park Ml'IIMNIaI I/N//nllt', Itnll.do, NY I I IN( "I K1NA1. ANALYSIti (11= T('1?I.1. NIIItS1:TS ANI) ('1.()NFti IN IIIIMAN KI-NAI. AL1.(xiKAl'f Rlal•.('1•1()N Wc Ilrcvitlu.ly rcllllttetl dnt i% wav rlnvihk Iu prllpa;alc aruvaleJ Ikl/atr-.I+1•cdlc I' IynqdNlt ytc. htwn hNlp.y U.wc d Mulwn fefu) a1k+Rra1(% unik'Iktnng a•pINMk\ 401 rcN•.INIn I Iw• ability 0 Inlefk•ukal 2 In ooI//INIIaIe Ihvl\111f1 Of NN'II /11 tY W. at Ilvah•11 I (ymplNrytc.lc/.llttn rnnfirmcJ by adr•f. hllfn tlcafl, lung, and iivct pr.dl.. Whlk 11 i% a k:lr Ih:N 11n•tl' 1% t•MN h/11CM IIN R'kva/N 1/1MMlr yft•t'iIN' 11t11111cf7Nlve aMt Cy1dIt111C T IynqllNtylc% in fcKtimg praflc, il iv InIpIf/aM Nl /nvc.ligatc IIk /nM.hanl.Inm by whw h J:unaKc 1% u/tinulcly /ncJialcd Whlk thrfc ie eva/cnce /11•u cyuMuac tcllk tan nlrthalc t1a11uFX. ININ'f r,9/MIfIV IMVe l'111IIhaNIIYf tlle l'11Mf11NNNN1% uI 11t•I111•F/ImhN'Pr .nt.v1% ul c•ru.mg rcNclNln vla a.k IaycJ type hypcrv n.ipv/ly bkc rcatlNtn '1'n cv,du alc /ht' t'tt111r11N11NM Itt uw6vlJllal cell .uh.cl., wc have u.cJ a ccll NMt•f lu c11fN 11 (1)J•, ('ItR•, a/NI a ptI11/t:NNln /d (I. 2 n'y111n.NVe (YH•/R• ccll. I.NUwI wplun tlw• } I:IIe. llK.c .ul..cl% wcre asaval hlt Jluww faytlgnilnln Iu lurthcr uur untk Ltanllmr 4,1 dK• /ntlt'c.. 4.1 tktlwlf rcrnymlwM by IynyllNw'y1c% pfc.cfll att Ihe .i/c. Id IL.IN• Inlary Ju/ln4 rcp•.INIn I lw•Ie wa. IcaJily Jrlcrlahk tklnllr yr•rlficlly with rc.lwct a/ pr1,1/1 Cf:1/NNl ln MY'tMMl:lty MI .K It~ h1Ah (1)4 •:wNl ('1)R' ~Irtc.l wMel.. hut anly Iht• a/rtc,l t'1)u• tcll. wctc .I+.vdaally cyltNu11lc. 'Ihr (1)4'I('1)11• t•cll.I:IrkcJ Junlw .pruht IUnt'INN1 III alkl1tN111• wl' have Inl'Ilaft'tI tklrlrV Irlwll hllllhnl,' IIIIu1N1m UI Iy1t/111wp y/l'% .•MaincJ It.nn hN/p.y tl.alc. 1Lr cklnal analy.c% ia11ca1cJ a fwuntauK-c.l cnnt hnw•lu IIw tklnllf..llt•ci8r IynqlMltry/es within Ihe prall hlMh hchwe vKmhcanl rn v/h.. x•Ict INNI (t'l/Nnnl,' wa% /Ifflofnlell within 411 hlqf\ aller CUIIuR /n11/71NM1) and ahcf 1w.s wccl,.ld Krltwlh in 11. 2. SlcpKa/, M• Htlyle. 1. A• Rcfkr, 1: 1• Irary• (' P.('tdvin, R 11 ,('u.nm, A It , anJ A'rrnn l, ! ! 144% 65100 7859 147

Iten./dlnl.Nw+o I4+NCt•Jlny. NNI).1•)4 197. Irhnlary 1'/R7 I hlw•t .n1MwN1 N.NItN1.J IN.tNUtc% ill Ilcrhh a1w) Mrrt 11 ul I)iow•. 11.0111 tlw• Ih•p.111//N•nt. +d 1'.IrM+h.Ky a/w1 Sulycry. M.L.:whu.cN. Grnct,d Il+t.pu.J. I1...1+N1 1 Wt 1('( q/1k 1 1 l 1W ('Y II )MI IR Y ANI) 17IN('TN)NAI. ANAI.YSIS (11 I N MI'II/ K'1' I 1 % ( 111 I URI 1) 1/t( )M IIUMAN I(1'.NAI. AI 1.1 K:RAI-1 S If)1 NIII I('A1111N 111 A ll Il 1' 1- S11H1•l)IM/LAII(Nd I lw• 14w•Maylr u1 I lynydwes'ylr .uh.M% prc.cM in tcna) hwy..N•..Iw/wrNF :w NN• s rllnlar ;Jl..yr./ll /cp't tu+Nl in .n I+:NL•/N..m t y11...1.Yrne have h'rn 1 h.w:N /c1 vcd In vru hv ulmnnwyt Iu./J l.a' .6unlnK, aMl ahrr c.lun.wNl rn rrh.. ln ml. rkukrn 1111 11 by Iwa t../.Y Il+.w t v/uow Iry• .+Nllng• aMt IuM IN/nal analya. Altct K h1 d1 .lay. ul .Yr.In tYhu/c• Irqh 1.•u I' (1'11.11 adl 1cu 2' I(Y)111 .uh,cl% were 1/N1rw1 In t•.w1/ t u1NUC• u1..1.11w11t1.N var/t•.1 Irnul ll I' h/ S O, whlch wa. Mw.1gndwatNly JNlcrrnt d1:1N /lw• rc.u11.1.1 /n vrY unowlwyK to.Nlav .I:IIntnK ul dw uncldlurcJ hwy+.y I IIC cuhnlyd tell.wrlcalnw+.t.Jllcu 4' 1('1)111.e11.1N'rf. • J1.whnhc.prc..rJlhcat'IIv,NNN1 n1,Irkcr.l)/(II11'<- • h1.Yw111w•11 21(•1)?SlrctephY11YS. t 41 11N•l.cu I'crll.wotc 1at1•11y 1 eu x 1'IIY) • h/. wlw-tc.1^ a n11MNlly ill the la•u 1' ccllc wcre 1.•u IS' 1(l)1111N+'( ' 41 1)ulya.m.1111tattwYl+tlNlt•Icu 1' /clL.t,uncJltNlcu 71x'<- • (b/ I ulw b+Nw1 :In,dyv% ill I AIN plnrlN•J I ru 1 1' .IMI I cu ! 1 p1yNIL/111M. 1M11 calcd Ih.N Itiu11 .ul.vt% pruL1.1.NcJ in rc.1+N1.r a+ 1•tah tW+MN rntlgrn. /n a tmacJ Iytnldwt ytc re.N nun t Ml k t.uNl IN+.Int ed 11 .' t hJv Nw 1 cu 2 1 I~yNILm~.n tk nwY1 ~Ir:111'lI t1+NMN ry•cdN t v1+N++cu .w N.+IV A IIU/NN .uhlry.d.+h..n ul r.N h t ul/Nlc wt'rt• M+th Ia'n 1' aMl I cu 1' 1: 1/'11 1 ru 1 I+r11. h+NN.YN• hny+.y wrn• INII1111•d t11 IMYIMy!t'M'Ity t'MI M'R I• aMI wt'11• I+N/1NI 11+f.INf- IIw- I t cll .Inu(•ru rcerIM+N t+NUplrt lt1('1)1/W1 tl'•I.cu •1 /.hutM+tdlct•+u+u1.NldlvnNwrtcawl/•.•nl I/1111K161 Ilw• Irn 2' 1' ccll.tlcnhcrtc•IrNwti•Jmt1w•k11 H.MN.Iw+wctlatly.yNw++tlc.:Ip:1.Ny 11N• I.clt 2' 1' ccllN wcre cap.Ihlc Id 11. _v INII MN Inlt•IIt'IINI r INIwI1N1/.M1 N+NM ul tIN• IN1nIN d culturc% tkawYldr:.ecJ NK :N uvuy A.uh.ct ul ehc IN/r11N J I cu 2' 1' t cll. lu.t leu 2' JunnK 1 Iu 1 wk in culuue• aMl Iwtanlc Iwu-2 U . Ihc.c .tuJle% provNle evNkrN'e Ihal dK ccll% that Inhletale renal alt..rnlt. JurinR reoccti+m /M Iwk alltyx+. Idcrauvc Ivnry+lw.kme pnNhN inK t'elh n/ 1YNh I xo 2' anJ (xu• 1' vuh.ch. T1w• I w•u 2' I ccll% are a1..1 hlKhly cyt.wt+.ic agaln.l tMNwN IynqlMlcytec, iMlicatmK the prc. eM'c nl hclla'r rnJepeMknt cyNNuaic l'('ell. A nNMN (wyN/Ia1NM ill LeY 2' 1' T cell• Iha1 Ih) tN+l cRprcv.IkIMN .peclhc IurIc1NN1 war ala/ itknlrlted. Prcllcr. l: I• l'n/vin, R It. • 1 rary• C. I' , Ilnyk, I. A. • Tuainn,1-. V, Laiaa+vN.• A 1,('n.inli. A H• arwl A'Yrnn 1, I T. (M• hNn11aI uI InInluMdlyry I171')) 2x2I 1N111• NVve1/lhtr 1• P1xh. 1 AIN•r .uly++Nt NrINNUI In.Ntulca nl I lcalth. Match uf Ihnlc.. Shrlner'. 11urn. In.ri lulc, l/c. N.n 1)N kln.nn. 11 S 1'uhhc I lcalth ScrvNe, MeJlcal Kc.carch ('t.uM"11 ('an a1I:1, a/wI ('111161 Med/cjl IltcnJ I mm Ilx Innnamy.atlw+lt.ry 1 trNt ++( tlw• Ikpannlcm o( Pa1M/1+y[y• aMl Trancplanl.INtm I lnd +.1 NN I:r1N Ld Cta/•I+.d \rlvn c, Ma..ax hu.ett. (:crlrral 11o.plt.ul, aM1 1Iatvald MrJN.d \+ b..d I1...1..n 1 1:XCRA('IIR(1M1)SUMAI. hNA S1111SfKAll•.\ IN I'KI: If ('Ii1.IS IINI)Iik(;() INVI'R11(IN l1K I)11.1:111)N A'1 IMMUNIKiI.I)IqI1.IN V•IU/1 1OININ(: 1NiNA1 t tirerN•rK•c% rM Iw1NIK unnmMlyhd,uhn variahk /MNruinm ate kMtwn lo he a..cn1 bkJ laNn vnrl:d+lr t V 1. Jlvcr.Ny 11)). aMl pnn/nK /1/ v'ynw•nt. hy .rtc .pccncivtct.NN hlnrawYl We INCwtll J M'M/IIYI '/IIYI' :Nwl rapl.l awly LN V 1U1 1 rt'elNUhmale.n Ih:11 N.r. pl:l.rnld I)NA t1.111.w•Iltly mlr.whNrJ Irtln Iraa.l.Nnwd prc-N tcll., aM1 IkuwNl.h,Nr. IILN IIk /YCtN1/1MIn:dNN11% Nwkrl9Nh•nt 111 a11y 1111nh1e 1'IInN1wNIN11aI l'INIII'tt. 1t'41N'/NY% \NIIIt h'III lu fINNt1111N' NYYN11hIt1:NNM1 \Ill'% :Yt' l IY11:11/k tI w/lh/n Ihl' K4 :I/N1 •11 Iy+ II.I/lk iny• reyt•tilvcly. 111c mur//1c 1,1 aMl V,I K yrIIM.•nl%, wI111I1/11CI1Nk IIK k/w/W11Iw•IN./ nN•r /wN1d11Mt V 11/1 1 pNnmy %lynalc 1)l'k•INNI aMI /nvl'f~NM1 tll'Cl/r :Jt ctN111+atahlt• InY11N'M N•• 1111m, V( I)1 I IIYMIIh111:NNM 111:1y Ir rl'LNlvely 1/1wIImllve tn 11N• I+yw+lul• Nal anallycnNln +d .Nr., a/w1 evcrN..N IIN' twn M.Vt•I IN1N'INN1% INtwlw'cd hy Uw• tl':w 1NN1 /Iiay IN' a 1 N111hYI Ik.v', 1 1: , Ll+la., AI R. •(iclkn. M., :Nwl Mtiuuthl• K ('rll 441 77S.7111. )wk 14, 1'1R7 / hhcr .Iry11.+Yt N:NwNlal ('anccr In.lilulc. I:aun IM• I.ahlNalury 401 Mtlkcular Hi11111py, Na1NN1:111n.INu1e ol 1)I:Ihclcc and Utgc.- llvt• aM1 KNlnry Ih.cax'., Na11wN1a11n.1Nute. u/ Ikalth, Ne+Ika/a• MI) INiVIi11)I'MUNI'AI. S rA(;I: ti1M:('lhl('ITY (N' T{II: I.YMIM1()II) V(I)Il NI:( Y)MIIINA I1//N AC") I VI'1'Y Wc havc csanllneJ Ihe level ul immwMlKWllwliw ~ene V(I))! rea'umhinatNN1 xirv • ity in a mnuhcr ul cell line, derived InNn Iyn1111w/id Ir M/nlynlplwlial IlneaKc.. Ihc a..:ly we cN/pluye.l u.ct e.Irachr.NMlwNlul I)NA trt .uhNrale amt thereby avuNl% d/1/N'ullle5 awq'iak•J with Ihe W[ n( l'/KtNIMMNH7/Ily /MeKraled .uh.lratc.. lhe rc cINllhinatilNl aclivNy .kcrea.ex during R-IyrnplN/wllkvchqNlrrN 11 i% hr4hca at the carlie.l.laKe..t( r..uanlncJ It-cell dd/ereml:NNN1 ard Ihen lall% pnlgrerv/vcly, rcat 11 inR untk/cti'Iahk kvcl% at Ihr noture N crll .IaKc. 'lllc aclivqy i, alw prcant /n nndlilYacnu:dp/1gcni1/N.ulmycMNJcellcaMlin/xe•1'celLhulMNm:aureTcell. Nu a1lrvNy wa\ In11MI in %Cveral MNIhCNWN11NNe1K' cell Itne• 1(el'11111hIn,1/NN1 wa\ MY'n INIly anwN/p wh.Nalc nw+kY"uk. which haJ replN:aled in Ihc cukarytNN ccl1. \cvtv.d p+..+hk nNe11Ne1 NNNt. trl Ihr% rcwll ae Ji.c'u..ed. I rrlrrr, M R.• Ilc..e. 1. E . Mvuua•hi• K• anJ (ielkrt• M (knccQe /)evehy+nrnt 1 751-761, 19117. (Aher.ulywNt. NalwYlal ('arxer In.ululc and NatilNUl In.lNUte% u( Ikalth FnNnthe I.ahINaNYy o/ Mnktulat Itinh.Ry• Nanalal (n.lNule ill I)lahctet and I)1Kr% live and Kidney I/1.ca.e., hcthe..la, MI) Itx 149 65100 7860

('AI'1A1('IN SI NtiI11V1. NI KVI S ANI)1111- ('!I'fAN1:1/11S A1.1.1'RGY HI'.Al' (111N IN MAN PI /\\INI I INVIn vl MI NI tN %I N\INtY N1111NN•11•I11n \ IN 1111 11 ANI NI AI INnd I hl• t'11r1 1\ ..1 IIN ,1) l:11M.IIl In Iq1'IrrJInKM tN111K l•UI:ItIrINI\ Irlltle fl•\(NN1\l• tt'.N- 11.N/1111I1N'r.I hy.1Ik'll'l'n t'tlMnltrl' ••r al/ll IKI. wrrr \tlNhctl /n lnen Atu1c rnp.•la, .11 IIN' I111111./11 ~I,/11 (n t.11N.11t /11 t,111\t'II :/ htlnllnl,' \rll\a1NN1 antl a t ICall UI II:IrC rl':N I IM/ Mn 114, wIN'.II /t-11MNIw I/ILNI tl'llt•alr.l •NIIINr11\IfY1NNl lhl•\C 11\:II fC.N1NN1\ 1/1 la(/\all'lll 1l1\J(>I.ra1C1I I IN' ll,llt't.Nn111NN'n1 AMI1M• Whll•t'llv'C /la'h/n~.Cn\a111N11/I Ihra'lllalN'• N/\ allrtky trJ.tnm t.. tJ1 ,INIyrU In.CM11Vl•1) /1l•OINI\ // i1111 II,'I: /n INNI alll'fl!N IN'r\.NI\ wrtr Iht•n /n.111,rJly rc•t11N.•tl fwo wrel\ af/er cap\airin pfclrratnlrnl /1,r IIJtr rr \INNIN• III .1Ik'r/'rl/ W.1\ M11 \lyn/haanlly ch:Nl/,'l'lI a'1NIII,arC1i /.1111r 11NNru1 tr.1t111N1, .Np)•r•tlnl• a/rvrrvhk' rll,•ll ut avp\alun IrcalnlrM 'Ihc wht•;d aoaqnNN•nl 111 11N• ,dlr//•y IN anll 1/•I Il•:N INNI Wa\, IN.wCYr1, n11t I/I/IIII't1tYll by CAI„aN/n INl'IIr.1111M'111, I/NIN IIInl! Ih,ll IIN' w)N•aI •IMI Ilatr a/NIII\Nlrnl\ ate CYnNeII by IIIIhYCfM /IN't h,ln/.nl\ 11 1\ t+NN IINk'II 111J1 1,11N,IN 111 V'n\/llvt• V'nvNy rN'rvC\ LfC 11/ /n11NN/Alt'l• I/N 1!N• honl•m t111d/N'INN I1111I1' It'\INNIy /rat1NM InI/1Nrd by alktRcn empl\utr 'IhN\, .cctNN:JIv tt'Ir.IV' UI IIM•,IL/hN., NN h J\ (•1 iRl' IN Ix hykinin\ Irl/rn .cnwxy /lrrve MarN'IN•\. Inay I.NII/1lNllr /I. IIIr II,/rr •,NIIIrNN•nI l.t lhl\ /l'aIINNI I uflhl•IIINKI' thl• 11l IIInK Y'n\:1 11N1 N•rUlv tt/1N• ,h•1.•INk•nl 11. ,, I,If/,'r ra1C111 Ln ta1/.aNm vn\N/vr rN•rvC. ll/lwa•.rr, 491.ntV IN'IVr..IV•1111.. h.lvr Ic\• rntp.tt.ullr Il.t 1hr whral rra.u/N1, / r., 11w IN,.1.•IN t•aU.w.l.Jlan, rf.INInV• I untlt.l•NI, I• I Nndlv'.c, I M Anl•}rld, A, an,l %rHC/.lrlNn, 4) Anr/ry a: 211 !%, 1'/N ) IhIN•r .1qq.Nt %wrd,.h M.'Ihtrl 11rvJlth l',wnld. Swrdl.h Wlak (nvIt..nnN•tn1 I uod. 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Ikn 1'.XI'KIiSSI()N (W 1111MAN ly(i StIll(•I.ASSIiS lluman imnNltNtyh.h/din (3 IIX(il ran tlc Ilivilktl Intu hlur .ohclas.r\ Ihal are .clrcUvrly r.ptr\.a•11 I tN m.larlrr, cathllhylhale anliKrn\ prelrlr/ulally Chr/l Ik(72 an1ltNNhr\• >whl•rra\ prldc/n antlXcn\ n\ually cIN:11 1K(it anll ILd71 1:hN•idallnK ,IK M.11//)!N'alha\NOI IIK V•h't11Yel•tI1R\V.N1/1111NV'I«(i\IItKIa\4\1\IIIIINN1:1111HIINIf UMk•r.laM/1nF' NItl1111nINll'/NKM1l•\ aMI It IynlptNlcyle IkvrhqNlN•nt *f// invr\//J!alr a'IInN a1/n1/11NIa1N"r t/I IRl i.I/IM I:1\\ /h'hl N nl'/r\, a vCn\/llvr iMI \ItY'Iha i\\ay IIa\ 17ah'/l Ilt•vl•k111C111/N II'( i\Uhl1a.K\ 11\In/.' 11anN'IC C/NNCIMfa1NM /IINNCN CM'C InIn1UM.a\\ay. 1'er1NNlnary t ImNal .11NIN'. h:avl• a1rr:Nly .IN1Wn /hn/ Inlrl'INN1 ININIr NNIIvN11/aI\ Ohrn have .rkv llvr IKI i? \u1N I./\. /k /i1ae1N y Nunnal kvr/% ul 1X( i2, IIUWrvef, Ikl MI f11lC INn an InU11utNMk•ht Ir/N y UI Ihe Inll•C1N.n IIf/Nle /nlhvldual\ IYraua' aN11C in/livltlnal\ 1..1v.' n..nn.ll lr.. 1..d 1/•1 •uN LLU•l and Irr INaNty tr.pN,avc I.I,/nnyrn\/11 hal lr/lr Il....l..u .n.r..,l /.......nh-,.nr nw.4'1...111., 11.G•.r1.yoN•nlIlavl•fx•cn Iwlynl.c\ n/uI1q1Ir hllral!a•S and Iq/11M,\c\ Ihal a It a•cll can raplc\\ INlly ..Nllr ly(i \ult L/\a•\ 11 ha\ hrrn 1/1utN! hy u.lhat anti 1'(• arN/1NNlir\ arr nN/\Ily (rl i2 w/lh ./NNr II,•( iI, :11N1111,11 Ilar V IC)YIM /It 11,'( il anl/ atNl 1'(' anutNNly 1\ ddlrfrnl Iflnn lhal ul 1140 a1111IM1,Iy lhlt IIINIIIIg• 11NYr111t1•, \I/I,'~,'C\l.lha( N aYII\ Iq/NIUI'llll' a1N/I•t• a1111MNIN'\ alr (mll}rny ul n1,1/Nlr arlte\Iral 11 ccll that ha. vl/l•ce\\ively \wnt•INVI• hul 1wu nwkpl m Iknl .uN'r.lfal It lcll\ ('t•Ihaar .hNlir\ u\ing p,lyakNlal acllvahN\ al\t/ \uFyr\I 1hJ1 rryul.utNy nN•% h.m1\1m lur 11,•( il a1Nl 11.•( i 1 atr Jil/crcnl INNn IFNIV Id Ir( i2 anll IFl'4 WIN•1/1IN• Iwn IlNltk'Ik arr tallen 1n1!CIhe1, we IaY1N IIIe /IlUhlllnl•agl• tNll• hrlll'1 IIIJ111IA' .In L• h • /! 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IN..Ktrsw.•ly wnh Inar I rcJtuw•nt with Jthy,k.. yt., tlrnl.nat H JrNI a'vcr.d JnJh.):. 111.11 INrvrut Jnlt/:rn s/nnulJlrJ 1' :wtUn Js.cnddy rn 11.11k t'% 4't'fl'1/.N1 .11NI,1rI./y. lla• Irrn•Mh.Nr .d Jnnycn 14, Ms I/N1' lysmr rrsislJU1 hN,n 1'vt.a tr.da.w ta•.MON'ut al... p•nnus dN• l.w/• rangc nv,vruw•n/ n1 Jnnycu rn1., surl.,, r ..q,. I1J4•J 1NI IIN'4' Ih.11 4'tfl•INMI I\ Irnl'Frrc.l by lh. :NI ,.1 a•, cIN.N t n...hnl,,ny .N by .1 IINMt IIVr.1 f . %t n.Vl .I.Mr ul IIN• t n,..Im1.rJ ,mUyrn 1/' tlv.'IN.N I,NOIdr. Wr I,r/hr.4' Inr1IN'1 III./1 ./IInF1'n .nnnd•MrJ 1' a.bn Jsrruhly l.N, I/IlNMr% 11t IIN• 1rJA%rn.N1 UI Jn11Krn Ipl .r. r1a.N ..Nnldc.cs I.. a I)NI' Iy.nN• rra.oot LNn, 111.00 J+n•s rNM uq'yrr s.ltrlNNr I w.. Ir,..d.lc- nN•.hJm4,.. I.r Ihr u.uf.no,n It, 1)NI' Iy4tN• rr.r.IJrNr .ur J.4a.4d %l•J}•r.wc. I (' . IlrJnon. (: (i , MJrlm, ) (' . I)Jvrs, 11 1) . .aNl O!nv'r. I Af (-yMmN•try /l 297 2'tt, I'1M7 (hIN•t .ulMNat AnN•rNJn ('Jntrr t/N'N'ly. NJIN,/1JI In%fltl/ll'% ol Ilrallh aml lI S 1>, p.uu,N ru ..I 1'rN-rFy I nNn dN• Ik•pJftna'rM .,1 1'Jtholoyy. (lmvl-rsity 4.1 New McRi.u, kh.Nd n( MrJ,cn r. AIINNIaI'f11/N'. :nNI I 1147 Slrrrwrs Ihvr.N,n, 1.,.. AlanNrs N:In,mal LatNaal.Ky, I us AI•mN,s. NM, ,ual l)rhJrtnN•rnl al 1'alla,h,l y, t LatraNrOr 11Mt hlvN lk MrJN J1 ('rnt.•r, IlarNwrr, Nil A k1)1 1•. 1 t tk 111C1 AM1NI 11'1'f 11 111 ?) KI'('fPlllll IIININN(: IN I'K( /1111(' 111)N ( II I I II•. I.YMI'll( IKINI . S( lUIH1 I: IMMI/NI•. kl -'-11't)Ntil. SI1I'rkl•s.I/K IsIK%t \.daMr unnm,n• n••I.•o4• .uMNrs4N 1SIKS1 Is an Inu,alm,.a(qNl•sslvc (a.Nrln IN.rheld l.v 11.1011.411 •m.I tnO11tIN' •111,IN.'~NN .r11% allrvalrJ by a v.aN•ly ul at7rnls Ill•. .n...' Iu.leuN$N• 1,... 1. ,n @. IwNtr.I N..n I/../N' 'UIlNr"•N l-PII%. IIN' IwnNhll/ty 111.11 11 a14t inJar-eJ SIRS Iu.Nlucli.m was invesliRala•J Iluman IynydwN: ytcs IrcatcJ wMh N) ' M fitslJrmnc hK kss Ih:m I hr reka.rJ a sup,rr.arve .nha•Jncc irMO a•ulturr snlN•t- nalants that was physitally. IunctirMaHy and anliRrnN.dly stmJn lo human SIRS ('rmctalmr anJ randiJrnc, slructurally Jidinct hislarmnr lypc 11111 2) nvcpl,M antal;o- ms1., (+revrntrJ lu.tanune-intlw-cd SIKS pnalaclirm. In lurthcr erlrrrrmrM., w~res- .i,at u/ htmran pdycHmal (KM 1'1(' ayarnats by (im A aml intcrlraM,s, .uhstarwrs t1u1 allw:MC Ihc SIRS p:Mhway, was inhibita•J by 11 2 rcrrpUK anlal;tarisl.. Acliva/hwt ot IyrnlAwK ylrs tn Ia.wluce SIRS by ( iMt A/w mlcrlrnms was bMn•YrJ by cimehJnK ..r ramlalmr '1 hrsr J:Ma tknaalaratc thM luralucti.at .d 3IkS is iralurcJ by hi.tamnw•, anJ rarsr tlr (rrssJ,drt y that I I: recqNnr hiraling nuy play a nrk in the SIR S palhwJy Srhn.q.r.t ll W. AarK. T M. anJ Kr,hy, R K. l1M• 1.Nnn:J ol hnmumd..ry 114(i)./INS-11Y/1, Aurus1 15, 1'1RT. (Ahrr .nptwwl N•MNarJl ('arwcr In.hlutr. I-nan thl• 1 kpJrtur•nt u/ 1'JIM,L.Ry, )rwish lhspilal tul SI I AN/I\, arNl I)r11Jn1nMnl%U1 I'rlhUlr/l'\ arNl I'Jlh„I..gy, Walh/nghal (/nlvCr%My Sth1arl „I MCJN'nK• tit I_..wrs I LYMI'll()MA M111N:1 C It1k H('1:1.1. A('iIVn111)N ANIy lY)t.l•kAN(T ' Ill ('LL1. ('Y('1.1: I)1'.1'1'NI)IiN('li Ii)1( Nf(iAl IVI: %1(iNA1.1.INGU1' WI'.III 211 11 I•YM1M1()MA ('I:LI.S IIY ANTI-µ 11 has IKt'tNtK incrca.inKly a~weM Iha/ H lyntltlwanas (auviJr cl.ara/ nark•L /.w antiKrn srot•cfic IynrydaM'ylrs and hK thc analysis u/1aMh prsilive anJ nr/:anvc 4gna1 hnl; m 11('cll.. In:NIJMiun, aMl-Ir, rCal,'CMs hare IK'Cn uNYI hr n111nN' an1l~Cnlh,Irl.,~rrl in thl•n inlrrat liwar wMh It ccll recrphK, al a p,lycMMtal kvel Wr have hcrn slwlywl: Ihc rllrch t.1 atni IK on a KnaM rrl umyue It rell Iymplamlas av oNNk'Is La cMIN•r hdrn,krna rn tmrnumTrnic signalling. (Ira'.uch hne, W111 211, has been aarwn to hr rr:MlJy mbrhitrJ in i1s Rrnwth by anli 1p reaKrnts We craNirnKtil thr .ensitrvMy .d Ihts tmr 1u yruwth tnhdnlear hy anli •µ anJ anti M rraprMs, aral drtr rnutK J ns linrlw s, yK•a'ilra'ity, anJ site ul lhr hMr'k in 1he cell cyck N the ( i,/S aMrrlace, la thr. rrpat, we have rnrMhrJ W I•.111 211 lynq,laana a•ellk a1 variuu. INanlv m(:,1n S and analyicJ Un c11rcN..1 anh µ un pn.prrs.Na+lhnwph S phasr (hu Jala suyKca 1hJt crMrc:J rvcnls lrcur rarly m( i, aral arc uniyurly xespive lo owalulatinn by antu µ'I la•v tnNhrs IN,w will alh,w, .rn.Mrvr nwJrcular ay,ltnrarhe% towarrh :ur unJrraaralrng ul H l rll .rynJl Irng, as well as na•IM.Is lu rrRulatr lynp,laana Krnwth l•.r a. S..Nr, I) W., LrvnJt, 1) . 1'cnncll, C. A., anJ KenK, 1' l.,urnal ul lixprnnwntal McJicinc IM.ISf+ IM, July 1486. ()Ihcr suplNat' 1I.N 1'uhlir 11ta11b Servire anJ the Irukemia titti'n•ty ul AnN•raa hrom Ihe ImnarnnhtFy and 1:> perimeMal'IlrctareWKS llnM., (lmver.ity ,rf R,n ccstrt ('arwa ('enter, k.Nhr.ar, NY. ISS Itd 65100 7863

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In.urJMr Rrpl.lrr .NI Ihr hJ4% nl thr unitple Nk'1111h1'a1NM1 nu1/11Kt a%%l/,•M'II hi r:ah Ptlrol.h ulvrn 'I Ik .Iwly vrlr. nw1.i.1rJ u/ d117 nwnNliy~,tMa• 1 MY.1 aMl'1I62 JvyF.da 11)LI .anw Y NYI Iwl/l 11:11f% hMNn IaeI1Mr I'/5R a1NI ahvr In 1975 AltnlytIN9, 2(.1 auhK•rl. In Ihr 4:rN•% h:NI IIM' 111!h11t1 tell•Ivr Irrt' InellNalNMl IIK fllrumatnNl ar(hr1t/V IRA) utMk'f 11N• SICi,ntr. In.ur,lntr Aa•1 IhaN ruvrt. Ihr rnlirr 1•/nni.h ppyN11J1Nm fhe p•urw14• t.NkawJJMr IN•ICrrual..e IlN RA wa.12. \ in MZ Iwm% wNl I S in 1)/ Iwul. '1 he agr :uNl va adlu.IrJ rJIN/ ul nh.rrvrJ prt rapeclrJ nurnh.n 4111 1M'twJJM p:ur.lrclJ/lvr rl.l.l wa. R(/ lur M% pair% a.N1 1/ hw 1)% poir. 'Illr.e /IYurr% arr k.wrr Ihan Ih14• IMt•vNNNIy 1t'(NK(l•aI tM IwIM hu1 1Y1111//Nlh/e wdh tr.u11. InMU /alndy .luahr. aNl dlr 1•'rM•IN' t'IN11111KIr nl ..1 RA. AINI, K., K.aRr/n•n.., At . Twwninrn• 1, anJ KaprN/, 1 )twrnal td Rlleumalobgy 1)15/ MMJ 402• 1'111b. (hhrr .upplw1 Siyritl luvhu.l-.wntl:NitN1 uf Finland. from Ihe NataNlal Ih/hhr Ikalth InUitu/r, Ilrl.inki, UinlaMl, arNl IkpannN•nt ul Ibhllc liralth tiaN•nrr. Ilnivrf.i(y td Ilrl.mki. 1 SNl)RIN(i AS A RItiK I A(`fOR 1OR 11('IIAI:MI(' Ill'ARI Ut11•AtiF ANI) S'1 R1)K1: IN MI:N 1hM al4N.•Ia11.N1 u/ .Mwing with i4h:N•mK• hrart Jivare aMl .uule wa../uJIrJ pnr.pt r/rvrly in 11MN nw n alti•J 11/ h'/ '1 hr okn wrrr a.krJ, In a yM .u.Ntna/rr 4•nl tu Ihrm, wIN•llKr dN•y .MNrJ IcrhlulJlly, Ifry1N•mly, .wca4amJlly, tw nrvrr tec..rJ. :nNl ak :uh a rrldN a1r. were t hl•aked l.u 1he nritl Ihrre yrar. /n r.lJhl..h I..w nlJny 1.l I/N.' nKn J.'vt't..(la•J 14h,N'1,/1l 11N:Ir1/l14'a4'.N a/./1it' IlN' 11111111N•/\ w.•rl• I•t'/ /'•• 1 161

1%. JINI -12. rc.lt•ahlt•Iv I Int•(• a:dcyunc.+d .na,r/nlt wtrrc u.cd Itw :m.dya. hab141.t1 .uN1 Ila'+IIN'111 \INqt'/% I/1 I~'/•I1. 11ta:141N1.1) %INKI'r% In -:r+I4I. .I/NI rNNI 4NNC1% (11 411111 IIN'•IFa•.Nlltl,tt'tlrt'IJtlVl•rl%kull.ah•tctnla INVr/d14•a4•Ir•Iwcrnhaluturll+lu.lrcqlN•n1 •/N+la'1\:IINIINNI 4N1rt'II w.1% 1'II111 1111I1:111NI I/N 14II;INIIIN ha'://11It4':/4'/+ro11+{.t' ++r 1r41t• ! 1)t 11+ 11111111 1 h.-rc wcrc /N+c.+4•. td .Ilukc :111NNIF Ilk' Ih- IN.f+'1• Ad1tu.l /IN'l1I hN ,IF•a'. I\4I% Ilt./,% /1Nk' a. I1t'r+Ny LI hY111'rtcn,ItNa. %/IN11.111/.•. ,IINI :III IIIN+I 114' tI/1I IN.I.irnlhlJntly tkara•.LC IIK ra•Llllv. tnh.. whNh wcre I 711p •1/1/S1 hN 1a11./rnnl 1N•JII II14'.14' JINI ! Illt Ilt' 41111) (++1 14 h.1C/tIN' Itl':/r1 IIme;Nt• J/NI .Ir.,{,t• at+nthNN•d AI IIN• Iry/mmng ul /+dh+w up In 1'rxl. It+2 or•n rn(r+rtcJ a Iu.Nwy ..1 :uq'ina I+t't Iul1. ++r IItv+4.t111/:11 Illl.l/t IN+It I tN IIMIt11111' Il'I.IIIVe rl\l. 1/1 14h:q'/11/a IN',Irt t1/4'.I4' IY'Iw+'t'It 11.0110141.11111101 /ICqIN•nt 4NNt'1\ JtMI nt+n %nlMm wll% ( N/ INS1. /+a nN•n w1dNNlt I+rc vNNt. /a h:N•nut IN•.Nt d/va.c 2 7? Ip- 111/S1 \m•u1n/• 4•cnl. w(+r .11r+N n1/.11 tk•tcnnar•ml 111914 at 14 h.N•tnti IN',Ir/ tI14'.11 •.I/NI .1r++Ar K..+1.Ntun A1 K,q+nu. I, la•Ltlrvl. I. I'.1rt+lN•n, M. 11.•tltI.A.t. K..NNI \.uNt \ 111111,11 MrJ.+,11 hwln.d ?'rJ IA 1'1• l.Ntu.Ny 1, 1'/N7 ( hlh•1 .ulyral I'.tavu Nurtn/ 1 +NIrNL11N+n 1 11N11 tIN• I A'/+.1/1//N'ill +/1 I'uh1N Ilc.dlh_ 14nlvcrvly ul I Irl.lnl.1. Ilrl4nll• 1+nLirNl 1 Ku.4r rn'rnt. At . K.qxlo, 7.,1'Jrtincn• M. • Ianginvainut,ll . SJrna, S• Rita. II , J/NI IIc/1,1/1J. K P.yt IuJlrt.l I t-noi. J\apidclncnlum 115.1?O, 14N6 IY+NII Ilta' I)t'1+;Ill/lN'tU ul 1'11hhr 1lcaIlh SCN'M'c, llnlvl'raly ul 11rl.mh/, Ilrl.ln6/• I 1111:IIN1 1t1 Sl(;N ANI) tAM/9 ING(•(/NSII)1'KAI7t1NS, KIiSl4)NSIi KAIfS, ANI) RI 1'KI SI'NIA IIVI NI:SS IN A I INNISII'1 WIN 1•AMILY SIUI)Y K/ll.h/lh ttunlN+y+l lll twin p:/h•nIY. thei/ .I+It114•. 7MI Chlklrt•n. 1+1-/a•r :1 H+IN/J uNl 1h•.dd\• %.t1111+IN11• tk•VI,'/1 IIN Il•%a'A/aIt 1/11Y'IN•IN' CIINk'IIINII/t4'y I•J/nQlc. ul twutm tk 41!N., a llt uNHCnl 4ulw Id 11t. .JU11d1111; 111t1h/l•/11\ IIIJI ArNC WIN /t /1Nk.•Ita•/Nk•Ilt II.NA 4'I• art• atnnl.nkd. tuNl IIM•v ak•.ign. pruvak unNluc evalualaan% ul nt,dcrn:.l /nlhlcnac., :1.4Ntd11Yt• /It.lU/lg JINI X II/IltO/!e. Ilnlttr1U11a1a'Iy• a•/IIININ':Il %I1NIIl•% alI IJIIIIIN'% ++I Iw111 p:ncul% h:lvc hlt•n hmllctl hy rclalivcly .null .antptr% anNl Ivy .a•II vk•aNtm M:IV. Inllln4a ut J•ac/ta/nurcnl ol IamdN'% I/tNn v/duoteaY twin rcocINnc• A 1•Iryc alNl rclxcvnlauvc rulN+rt nl nNllNt/yrtMN' a1MI Jvyptqn• Iwnt p,ucnl.• a1r:Iw111ttNt/ a IMMNII:NNN1 IIJNYI twin rCl,'I%Ify• I+fUY11/C% lhe /MMI/IIJI %AIn(1I/11l: 11.1UN' /ar twin lanuly rc.ca/ch. •fhtI paper nvicw> l1k %;mtpling con.Nk•f:uN+n% nak•llyln4 11w inu1J11:1Ullly %IINIy hdrC1l tN111N I'111f11-11 1 wln ('u1N111 :11N1 a•vJI11Jh'% (M' fa'1Nl•Ne11/allvr rta•.% td dk .alnpk•J Iwtnc. Spnu.c% antl a11oN t-hlklfco I/uver IN yc;lr.l ul 2 lb pJlr% ul 1w1u.• a1NNu equally Jivwk•al by KcrNk•f ;aul iyrualy• were cvalladcd by a Iwn6d arN•.1Nlnn:ure 111411101411121 reyNllt.c rJIC. ctcwyk•al Rt+'.(. atxd rn 464 /11 dtc 472 nul lcs I:IIIt1IN% ('/}I 1'{•), A1 Itihl tMle nll'nahcf OI /IIe Iwln*\ liN11/Iy C1N11111CIa'II 1IIl' qIN•.NtNt- lu/re 11w• .://npk•tl Iwin.• aekcled llw Iccurwbly lu nuttnliic .lau.tN'al puwcl al dk• uM;nnavl dala• wa•rr Mlr.nlly reprc.cnlalivc /d nnn .clrclral Iwln% dlJwn Inml Ihe (*111NK1. W/III WIN1111 thl•y were na/akd nn age. Fentk•r, atNl iyyu-my Slxh ra•.uh. .uyyc.l Ih:x Ilr• 1'tnnl.h (•uMtn hJ% c><cclk•n1 plMcmiJl luf calcrNk•d Iwut-I:unlly re +car.h /k4gn. K;yxal, 1, Kt/.e, K 1, Satna, S, l.anyinvalne/, FI., Am4.nlNa, M, Kna, 11 ,•J/NI IIcILLIIa• K. (`(M)K SI 1 11' V1IAI 11 Y. 1'M(/II/INAI \IKI SS ANI) MI1KF111)Il'Y A:ilX 1'I AK 11)1 111W 111' \I111)Y 111 11r771t 1'1 K\IINS A(;11) 1% t+J 1'1 AK% 1hc o4u.dlly t+1 .Iccp 4.1 111779 1 Inn+.h .Nluh, aycll IS tt+ W ycar% w.t.:+.lcal In J I++.Ld yur.ht+nt.urt• ul 1'/IS SIrrp yu.dny w.t% y.ttalpt•tl In thrcc aalcl'+NN-. F1NMl I IM'x 1, ymlc g+Nr11S1Mi 1.Int) h:N111:'= ) I IN' 7/%4+a/:11NM t+I IMNN Ah't'1+ tlW+llly W/III tN•ur++li./4n, .Irc..++/ d.nly NlrvnK.:utJ hh Jt..Jb.l.t.bon werc vcry alcar..h.+wtnF I'+NNttud/lyul.kcpr++rr:Lltrd 1tdluwml! at+rrclalN.na+~'llan•nl. 1/ 11•11 :2:uN111 211 :Il.u Nt.IN+A .kcp hrnylh Ir - 412 (1 alNl ht urN•Inphtynx•nl (1 // 111 IlNhvrJu:dk wcra• 1n11nwca) up n•/ny dlc clNUpulcri.ral nalNmwNk rcyl.Nlc% lu ct.lka'1 .hvlh certdiaalc% a1N1 hl+.pdal rlY•1MtIv I'crvtn yc•Jr. 01 lulktw up wa% atan- I+Illctl unlll 1hc lu.l cvcnl t+r crrl ul I++ll++w up in clN) ul 1v1t1. Ay,cathuclcd n-.k r.dio. IKKI htr h:Nl .Iccp quullly clNlqtar.•d tt+ ytNNl quality wcrc calrulalcd ha Nren alN) wtmun ul nJlutal tk•Jdt.l KK llx Nkn 2 t,/l• ••, antl hw wthncn// 42 m)• vedcnl.k:nhc 1•t S'l••• 2/.1 n./. InKnl;d lli4takr hn,lal:JlvalaNll+t .uN'Nk /2 Kh"'. 2 21/ n.l. IN+.p1lJlivJlit+n thK• It, IN•unni. 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MARY \11 ANNX 1•AR\III I:Y, Itit 11 1:1)WARI) W W'.I.IKAN, M 1) (llaeman, 1)cparlmeM of Pharmxoh.Fy .nd I:yurimcelal Thtra~euln-., 11u.ww VnSrersNy Schm.l nl MeJN'rne, N...h.n R()R1S M PITI?KL/N, M 1). A..IS1aM PnJc.aw ul Mcdlcrnc. Scalww M Rheumahrh.fy-t'hma'allmmua.A.gr. Ilntvct.dy tA ( aldmnu ScMwd ul Mnh cinc, San 1'rancl.co. IM:NNtS R M:TERSI:N• Pn 1) 14..Ic%aw ut PAatnucoh.Ry. Ilnlvcr.ily ul (•trMwadn Sch.wrl tA Pharmaay. 11rwWcr CARI• W PII'.Kt7:, M 1) . Ptt 1) I41Ars4N, I)a•parlnw•M\ ..1 1'atlwJ..Ky and Mlp.i.n.h.gy-lmmum•h.gy, Wa.h.nrhw I/mvcr.ny S.'Mwd tJ M.Jtunc. Ihrcahr, t•a1MJ..~r aml latwwanny MrJ..rne, Ihe kwl.h 11'..InIr11A S1 l..wl., \t I•.wr., Mt ). MAI•('(11•M C. PIKI:, PII 1) 14u1e.ww n1(lwrunumly MrJiane aa/14 dta/tn•s, I /auvcnny.J \.wllw•tn l'althrnu Stlwn.l td Medianc• 1... Anltek. 1)TAKAR 1 1414 1•AK, M 11 , Pn 1) liaa'wivc IAtca.K. Ih.vct McJw:al Rc. .ear.h ('cnler, Inr., Ih.ver, IH•. M(AtKIS POI LARI), 1•a 1) /htcr/.w, L.IwnJ Lalwaa.wy. Ihnrcr.ny 411 NtMrc Uarnc•, N.Ntc Uamc• IN C. M P(NMI:RAT• Pa I) Ihrct irr nl Hi..M.Rn al Kc.cata lA, Pa.a.kna hwndaluwl LM McJla al Rc4•arth, 1'a.a dcna• C'A S H 1'RAI)IIAN, M 1) , 14/1) hu/csuu .4 ('halmav..InKy, 1lurarJ I/nl rct.Ny (•.AkRc• ../ MtJn rnc• W a.hmRhw. IK. 11 R PRATT TIK/MAS, M 1) 14../c\4u Iq Pa1MJ..Ky and Ikan. MrJwd ('dkRc td Gwth l'aulma, l Tark.wm 1•111K'1iS5 A~,INSIRIIMI{NI\ (Y/MW IRA 1NM/ 1lnwilyn, NY 11 KAt 1) A Mt1t'111 I I 1'tl 11 A....ul• /'.••/•..•w ••1 An...•rny W ).r \Ld• 1 t..•,• .,,1. \. 1....1 •.1 AI• •h• ur- 11 hv•••1 MI A.a.lan1/1.JtwM.AAn.aanr in(MnlelrK~ ll.lumMa I'nnvenllr ('nl anJ l:y~nc..d..ley4 kKe ..( I'hr.w tan. & 11wKc.wt.. New Ytrt HLNI)N'111 1/ 1'Alll 1. 1) V M A.4w lalc 11.Jr.4n nl 1•allw.h.Fy. Ru.h Rr.hyk'nan G 1 uke'. MeJw al l'rnler, / lu• tap.. MAkTIN S I'Rl)1/1-1., it 1/ S (lntl• 141wlmrwt n/ (hal Pa1Mdn~y• Nc.rrt ('Ny Ilnynlal. Ncrratt. N/ WII t.IAM A PIIYt/K. 1'u 1) Noyd PuJc.vr .d l'htnn.lry. 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M1l'11A1I S RAHCIIN• M 1) Ke..vlah C..ann.1, I alwwallwy al ('alh.J h.l•h N.nl.rul l'anarr In.tnlwr. HrIM~.Ja. RI)NAI I) 1 RA%MI/C\I N. I'll 1) A...w late AJluna t 1•r.•Ir.vw. Ik•ParlnwM% ul Ilm.mwlNy anJ I nvu..nnlrMal Ma11• Ilnc. Ilm.cr.wy .d ldd.wnlA lldkKc o( MeJp n.•, Irvule. ('A WAI II k R1 1NSl'11• M 1) A..+•a.alr 1•ndc...y .4 ( Lnk al Mrdn /ne. Nrw Yo11 1 Imvrr.rty %. M.J ol MrJw nw, anJ Nl'1/ kr.rat.lb Cr/vMr, (:.Jdwaltt Mrnrwul (In.Pt.J, Na•w 1.w1 I IMI)111Y I kl GAN. M 1/ Pr.Ar..ar .4 Mrdn.nr. 1)ncal.w. 1)IVl.n.e 1•1 ('A1,In.vaN tlLlr 14.ta.r.. 1'/J6 orr ul Mr11N/M' a/wI (A'M..Ir~ .4 Naw Irr.cy, Nrw Ir/.. y Ma Ja al \, IrrA, NcwarA WII I IAM 1114.11 \I)N M I) /'H.Ir.wa a/r1/-hauro.n, 1lrrahmrnl .4 M.JnaI IMN.•h•rv• M,.1.a.1 (•.•Ihrr .J V///'m.a, Kn lan/•.nal 1 YNNI M k111) M 1) W.dl•.n h I'r.dr..•. „1 Patfw•1••ry /In.A•J M.Ja al \a Iw.•1 1/.•.b•n 1 h.u.n..n 1 h' P.u/uw nl .d 1'wdnd.• ~ 1 h./Jla n. II••qn IIIINARI A RI IMANN, M 1) 1'u.lr.vq Id M.J/. nn, Ilahncn.ann MaJr a.11/'ad1YKc a1N1 11•..I..lal. IT/I.Wa If.h/A 111!1NRI-Ml11.1)1) Ix)NNI I1..1'u 1) I'nn..ryl kcvar. h A...•aalr. 11Ar varJ h1l'dNal %.M.J, InvC•I/ra1.M, ('eMr/ l.w 11h.r1 kc.caah, Hn.lam /tHIN E RI PINC•. M 1) A..r.(aM Ihrr.hw. Wchh Warlrl I.~nK In.INWr: A..rc ralc I'role.•Iw u~ Mcdl ./Ile, ltllIVC/•/1y .4 (lJ.wMh/ Ikahh S./ rmc% ('rnlcl, I k•nvr r R()HI RT RI?SNk'K, M 1) A\M\ lalc Pn•k•%.rw u/ Rfl1r.alwuve MrJ n Im•. I lnwrr.ay u1 l'a1111wma McJn al CcMCt, San Ihcral Ill•R11I•kT Y RI YNU11)S, M 1) 1't.dc...w u( McJl.lnr. 1kw/, ILlnraary %ecn••n. Yale I/n/vrr.ny S. h.rJ ••1 MeJ/. ./nr, New /laven, 1'1 141141 ANI) 1 kl YNtN 11\, M tl A..../.M Pa.t....v ..1 I'.d•.d..rv 1 h,.vrr a. ..1 1.. \...../.....,.w VI('f1)k RI('11AKIri, M 1) ( hw•1 n1 Xurprry. Prc.hyl.•n.m k1rJ/, A1 ( 'a•Mer, San I /.aK La.. VIR(:INIA 1. KI('IIMI)N/). 1•11 1) Rr.car.h A..awlNr, 1•aa/lK N•wlh..r.l kc.car.h I.InM1:Nnm, %ralrk. W.\ ARNIS RI('111'1,RS, 1`I/ 1) A...¢ul.• ('ruk...w..l l',nlr.hlrv • I lmvrr sny o/ ~rwlM•ru l'aldlwnu S. MrJ ul Mc.l . iainc. la.. Anra•Irs W11.LIS If RIh%I:N, 1'/l 1) Sennw HnhhrnlNl, I lir kn•n.-. Itlvl .nw1, 111 K.•vvah 1n.twWC, I hn ara 1)ANIH H k11 KIN. Pn 1) Ava./anl Pu•/r.v.w J 1 llrnoa .J lhe R.r\elrlla•r (lmver.ny, Nrw V•n\ R 11 RH:Ik1N. M 1) 1'Y.Jc.+.w ..I 1'a1h..h.Ky. llmvrr..ty .J Tc>ta. McJn:a/ Hramh, (:alvr.tlr. SYI)NIY1' K1111NI11R17.Pnla 1'wh•.4w a.l 11.wlcn•.h.py. Ilmva•r.ny ol %.WIIw'In 1 ahl,Nnla, I In Anl•a Ir• I111:1NU k111(1kIS,I'u1) kr.rAa h Sa wnrl.l. ('/ly ul I I.qw- Rr.raa h /n./nurr. I h.al/r. ( A III N\I1N H RI)P. M 1/ A...wutc I'r•Jc•ww ad Surra•ry . /'hwI, ('a/dlaa Sw •a•ly. Ilnlvcr.uy ad (.Id.wma \aMrd a.l ~cdn.nc. San I ruwl..la a()SI.PII tl R(N:/:R%. M 1) lhdy Nanle ul lc.u. Ihr.(w1al, GaJ.akn, Al.. RUH/:R"f (' R(KAN, M 1) As4Rta/c Pa//csMw uI PatlnllaakZ anal Pc dultlc., S/ lawl. llnwcr.ny hiral n( Mcdn Ine; A.wt ialc 1'a1hlJlryel.l, l'al.bnal (iknmin Mcnuwal 11u.lnlal hw ( hllalrra, SI 1 Iwrs, M( / ('11AR11:S 1. R(1SIi, Pu I) ('IInN' Ihrel'hM, I)IIC.11w, N.rmaovc A/t (np Stuwlr, Vrlrran. AJ/wrn/.l.aln.n (hN Pa//rM ( hnN, Iln.hw/ H)IIN A R//SY('kANS, 1•u 1) Aswrcrale Ptnlc%..w .J 1'bxnla.nl•.Ry, Medical CnikRe n/ VlrRmla. Vupnu t'.wnnw.nwcahh I /n.vrmly, kn hnr.m/ 11 111( M R(1CC. 1Y/1) N. .r.a h A..•. ulr 1 hr R.. trlrlla. l lrn 1 )/)IIN R RI)WLANI)S, Pu 1) Stal/ tian•ML1, Saulhwca Rc.ench tn.U- lulc, San Anlunn., l% H1•NIAMIN A k1IHIN, 1'(1 1) A..LIaM Ik.dc.,.w.J Puhlm: Ileakh, Hay• IIw 1lnlvct.ny ('aJkke..t MeJlclne,l/nu. LM R/1NA1.1) P KIININ, PII 1). 11aAr...w 401 1'hnmx'ola.Py, Mcdical ('IJ Irpe .4 VlrpMl., KKhnwwnl. I/I:NKY I kllt\I-.K, M I) Prr.nknl, Thr ku%,cl1 1•Iwnlalnw/, Inw., Slalcn I.land, NY W l' k11SS11 I, M 1) llnlvcr.dy 4.1 Ir.a. Medic.) ('cnlcr, 11,w.h.n WAYNI• 1. RYAN. Prl 1) 11.Ae...w /11 Hu.hcnu.lrr, Ilnivenily .d Nrhra.(a ('.J1cRc 1/1 Madicrnc. ()maha 1'I 11:k 1 SAI 1\1WKY, M 1) , 1'hl l) IIraJ, hwrnavr 1 rca/meM ('cnlet. Sainl I...rph Ilu.lwlal, Hwhank, ('A. I•AI11• SAI : f MAN, Ih/ 1) A..Ltanl W..Ic...w .11 Hi.whrnMUty .rnl Nutnlwln, 11Mvcr.dy.J Srwlhcrn('aldd• nu S.hawd u/ McJ.loc, lan AnKclrs. MAIIkK'1: S SI:(:AL. M 1) ('hnw d Pt.dc•vw u/ McJrclnc. 1 u11.11M vcrvly Sr1u.J.d Medn.nc. Uara.w. IA• ~rarlmrnl ol Inhalaunn I hcr apy. 11o.1.r. l'ny Huynlal, Hn.h.n ('ARI. C. SELTLI:K, 1h( 1). I/.wwwary Re.eanh A.wlriae. PeaM.ly Mu.ewn, Ilarvard Ilmvcr.uy, l'aM txnlKe. MA. 1L1 K'1t 1 SI : V I:R1, h1 1). Ihtcchw and Dean. In.lilwc u/ Analomy am/ 1'a1M.M.opy. blvl\nM ul ('amc. Kr %tar.h, Ilmvervly ul 1'crvRla, 1'cruKla, 11 aly ('11AR1 ES R SIIAW. M 1) l'Mc/. Scclnln ol MrJ.. al (:rnrna •. M 1) Amkt..ws Ihr%Iw/1I and 1n11Mw hn1/11NC, Padcva.w 4.1 Hnd•IKy. Ihc l/nrvcr.qy ad 1 c.as al 11.w.l.wr ('HARLESI:. SIII:RW/KN). M 1) As.r%lanl Pt.Aes..w ul RadnlhlKy. Ilmver %ny .d kaLhc.lcr S. Mw.l nl MrJK Inr and Iknl/.lry, Rrwhcarr, NY S111)11 S11111A1 A, M 1) . PII I) 14.Jcsaaw Id 1lhawwl:nul•.Fy. l/nwcraUy ul Ilawail S.hInA.J MrJnrnc, IlawnJulu NRAIIMI P SANI. t'11 1). 1kad,1'ralrrn Hntihrmi.uy, S.wlhcrn Rc• .carch In.leulc, HnnminlCham, At.. I II .Rll'll 1/ Sl'11A1:PP1, M.I) IhrccMw u1 Nrwnpharrnac.Ih.Kr. Mav+n I(e.carah Inai/We. W.wces(er, MA X)Rl:1:N l/ Sl'111Ja:1:1., M 1).. PH 1). 11n/eWw anJ lbawnlan, I)ePalmeM d Sur~trry, lulanc llnivcrsily ScAlwll u) McJnlnc, Nrwa Ihkan., I.A. ALVIN R S('lIMII)T, PII 1). Il.rcchM .d ( inmKl/nR, Tdu Universwy, Mcdhwd, MA. IAKINI S('lIMt1)f, M 1)., P(1 1) AvN/.l.nlPnJc~..wuIHNK'helwiMry (hvi- .nn1.J Iln.l.~(N./ ~r/cmcs, Sldc 1lnwcr .ny u1 Nrw Y.wk N Slnny Hnrd, lnwly 1h..IR ISAA(' S('HOtIR, 1) 1) S., Pw 1)., D S/'. Ikan, Ilnrvetslly d Illimwa Cu/kRe at IkMlslry. ('hlcaRa Sl RIIM'S ('I INI(' ANO RESEARCII It)IINI)Al l()N I a (hJ1a, /'A 1:1:RA1.1) SIIKLAR, 1) 1) S. ( bark. A Btac\cll Itole...w rl( ()ral 1'a Ih..h.Ry:llcad. 1)cParuncnl al Ihal Mrah• tlnr aml ()ral Pa1MA..Ky, IlxvarJ S.Mwd nl I)eM1I Me111\1nc, H.NNM 1)AVII)1.. SIMON. M 1). IwNnwhw.n IMctnal MeJicine. ('in.'rnnan ( irneeal Ih..plaI. ('In. raaau.1)H E?RIK SKIN/IN/, M 1) (lwel. 1)clwlmcnl nt Neun.hryty. Hrylcb- lerK 1hnPrlal, CnPcnhaRen, I Rnmar\ Kl)III:RT ) SKLAREsW, Pu I) Reser.h Aswra/e Ptrdes..w ul 1'a1MJ r.Fy. New YrwR 1lmvct.ay Re.ran.h Scr vn'e, (:oWwalrr Mennwlal 1loyulal, R.u..e.ell h•and, NY NIK111AN 11 Sl.(MNIi, Pn 1) PYdcwwd Hn.nc47m/.uy, lhc Iln/vrraly IA ('cnncs.ee l'cnlrr 1.r Ilr 11.v1d. S./ ences, McqlMs HAN(K'll SL(Nt, Pn I) AxYKla/e P!n(cfMw .d /luman Gcnr/ias. Saalikr ScIw.A nl Mcdwlnc, let Aviv 1lnlvcraly, Tel Aviv. lan-1 1 a 1 191 ~

TI11 OIK)K1 A SI I)I KIN, 141 1) A..Ll..nl 1'r..lr..w .4 1'harmx.dryy, Ihr\r I/mvrr.nr M.'Jual ('.•nlr., IAn ham, N(' I:I l)R/:1 W SMI 1// MS. MO A.wul.• In 1'.aMd..Ky. N..Ihwc•ICtn IIn1..r.rtv MrJ...1 \.h.w.l, 1 hn•.Ku 1)I NNI%M SM1111. I'n 1) A..Llaul 1'r..Icwa ..I 14.d.~taal S.t emcv, Wrlk.k'y l'..1kFc• Welk.ley, MA (31 NI. M SMitll, 1'u 1/ A\vlNant R..Ir.vw ul /'.y.MJ..ry. Ilar vaJ MrJr. al \. M..1, Ma..an ha.r•nv (kn rr,11Ilo.bn 1 11('ll.l: SM1111 WI 1) I'L.IC\VN .•1 Itnahenn.lrr I)artrmnNh Mr.lnal Sah...l, 1lamrvcr. NII 10111% A S111 1111 , M 1) lllan.he 1• 1 rvy Ih.l.nrur./n•J %rr.nc Ptr.la•\va, Prulr\..a ul McJn/nc. Ouc. hu. Rr\c+r.h I/PId I.h.w.awyI fcml.k (lmvct\IIy /lcahh \. n•mcv ( rnlcr, 1'hJ. .h•Ipbu SIII.I.I)ON (' SI)MMI.kS M 1) Ihre.hw..1 IAIra.Iwlr.• I ea.. 11d11/o. pItal.(lrnk .11'u.lr...a u/ /'•nlwd..py• 1 0 IanAna I Ilnva•t.n ( 1.11cKc ul ITy\n r.n. A `YtRt.N1.. Na•w ?.uk 1 RNI ST S//NI)111 IMhR. Ihl 1) Awti lalc 1•rnlr.\.w ol Ib.n Iw ou.lry •('.J kFc.d I.nr.lty, Sl.tr Unlver.uy.d New Ynth, tiylxu.r t M SONNI R(NIN, Pa 1) 1hv11nrut.hcJ Scrrnc PruIc.vw u( Y.ad I.gy, Ilnhana Ilnlrfr\Ny, I(kaN111nRItM1 SAM SORI)1'. Pn 1) Ik,ul. IlrP.nlmrM 401 Ma.r.Inn.kaular ( Tww1.11~, Ihr In.l8u1.• l.u ('.ncer Ke .fu.h, 1'h11nk•IPh1a S/III111W1.SI KI SI'AR( 111NSTIf111U. San AM.+Ia., I X 1)AVIIyM \I•AIN. M 1) I/nrvhn, Ih'p.rn.wn1 0l Palh..l.ryty• The IIr...Wak Il...pa.l 1.n1.r, 11u.ilyn, NY AI 1 t ANI N k\I-4 u M M It .A..•.LM 1•..d..,. ..I 1•..L.uw. Ilutr 14u....... M. •1.. .1 1 . a... I..../..n. Nl I RI III RI('K I STARI•. M 1) 1'rolr\v.a..l Nuln/mn. Il.rvuJ Ilmvet.ny S.M.d ul Puhln 1k.11h. 11.n1..n NORMAN (' SfA11R, M 1) 1•tnkwa .A Phy\~nl..ly, ('..Ja.v... al.n kevx.h In.hlulr. Ilmver.Ny .J l ahlor n.a. San FrancI..u (:I:INIGI: W SM1 1-11RS, M 11 /4vuxiMC tn 1•.d.d..ry. N..Ihw..lrrn Ilntver\ny MeJn.l SaMad. l harF.. JACK P STRI)NG. 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