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fO'lr Detai ls]

__

-',

'CQiV,ER
lfhl1,AMS Anj'iiLmll. ,1Miee'ling in ~Ol5tOil1l, 14 'N~18IF'~lrual~' 2.000"e>;plol'es 1mrterd ~~d ptunifirry' Ir~earrn iii mI d d~nlQI'I~IJ'i;Jte5~Jrn,~]plflu,~~~,f 5Clence' ,and t:ecl~nQ~,ogyOf! s.Qdety; TI~ meeting b:r~lt1lgS rt.og'elh:e~il!divers!ll aUirraJY oo~eadiillg :srie1il1llilsts, enginleer~. edlolcat:o~s,. 1I1ld polfcy'ma:ker,s;.Seethe A.IIl!.AS,.Moo'ling Program b@gii'ilnli'ilglen pdlg~ 818.
Im~': DmJme ,t/l,OTWOtid {phoMmJets~ USDM

709
711 717

Sd~'n(e OnUliu:: lhil~ Weekil'l SciMce

~ditn.~~.' (hQiC)e tOl!rta(~ Silence 723 Ra.nd'om 5aD'l~res~ 725, N'~:s~abr'S81 a,AMS M@i!tifiilgl Program 833 Sc,ienr,eCa~eerli

720

,EDIITORIAJ ..
715 Mpro~il::hin9Sd~oo Df D'Ollald.Kef11J,edy'
>:>Ji'f:!'f'lll"dJAdides M. 7tJ6 md

?1?

NU!!WS OF THE. WEIEK

CDI( ,DiirlE!'ttor':s M~'!I5.[Iglemil IIili~kRun'5 Ahl!1!ll. of White HIQu5i~~d~iL§, IiJwone SI!fV P!~l"1e' ,",e~p:s Fig:M Calh~rlQrf!~aJ~ire'S,n7 : 726

ILIE,TlER.S
ShePIPirlg fow Expliimati'Drli~ E:, Mi. Brum/Jet et aL Rie~PDI1i~e M. .KfiOMa'Wel at. M. Tllile AlB's. IIlf Multiple: ~Qlndilil~, 6. ffentJ1f1,g emu' R. TonJ~erIRespo~$e t: ~nhold tJ.nd C. ,R. ,[am:J.i!> COU:Eal(l~S 729 AND CUJUFlltCAlUONS 745

Tum~H SUpp'~50r May Al~oArr:e(t Gestalti!l!!1'al Dill!betfs

::>:.-

729

l1~po.rl p. 8(16

:SC:IIEI~CI~S(i():P~: P~f!lagon IWse!iilrr.:~ (Illiflf Seek'511 o/~Boo~:lin 2.009 iCaUi[omtaJ S~if5a $600 MiHio'fillP'llt of S;l1b.niollls ~Jecol"!~tr~ctingthr~Qlijgin:; or the AIDS [Ridl@ 1iliI~!c_ FirOO'l Arch ~w[j ,ifill" ~so[a~es: Sg,enti~ts f~te China's S'lIplremJe l~olYlifl:clthi

130
730 73~

IBOOKS IT.AL
DI! MllIst,llmpgrtam Fis!il·it! tbeSea, MJml1aJd~i1 ,anod Am~rh;,al H.8'. Frfilfl.fi:lifli, re~·fW\ed.by D. ,Pauly

7SQ
751

II'!t~S'lladow ~Ul'iiii M,oiWi D. ,Sftji9·~o!it .Ditt':crO$';. fWi~wed' oy ).,i\\'I.

Pos,ot:nolf

N!EWS FO'CUS
Who OwniS·'G'~y'((lblolog:t? Ii ~b to G~t t'1ll~M~:slur~ of Maltet
Te's,tinQI the Line l3elw6oo Too MII:.d and TClIOI Uttl,e

ATMte ,oHllile ,Giorma, Stimti,m AILinr:lI~iilfI ~<I:5it ~~ OrPHne f~tmC~ p, 7I'J9

7S0

734
738

[10 Wal'llCi!!rln$l1 A.!.ba~roSls@s; C,ar~ AbDut Ma.th?

740 742

(ol1lffooong iOtll'l.1,s,terIWSSE!'~, L. &f. .80IJWer et iilt

753

IPERSPECTllVES
,Atcmhtire MGgirm. tll,S't,t'l(,U-ffl ~>RSl~;d:l
,4"

-~-

754
,QJ"j{l'l~p_

Tn ISiS

.AU aJ1i: OlllWe: (amiJen ;50:;> R~arI: No· Prowmo\fl

[I)"

188

R,eglJ~fed
:';>0

756

R. fl. rJ(Jbtre~

Rq.larl" 783

A [lcckw1tal a FllR; SlWitchl JL C PD'ofJonfJ]. E.f&'te"{ jf.

~=- RfPorr p. 8{W

76";

1ST
7S:a: 759

A~iE!IjIiI'Stam of QU:a,!il.tUiIi'll M~tt,~!, III: .N(J{]~(}S~ ~:- Ihf!rotrh jlrjl'd~p.

Mirnill'liJ ~orthe Il[phem~r:ilj~

G. C Bower »» .R~ar:r p" 1n

703

Science,
PLANEliAffY SC~IEt\IC E PHYSICS

CONTENTS

Modelillil!!! tlile llKall:iz·ed·te·ltil1le:ralilt UE!(.tr1ll"1lC ir'all1Jllalili1!OriI, rlil the Heavy Flllrmiollil Systellil1 (IEllrll'lts ). H. SMm_ K liGule.; G. R@t1klf Fir5t."ipriliiCip~.s UlllCiJli!t[o:ii 5 w~c~~fu~1y d'i!.SLrib~·~~octroni( ~fan5ilion~·if! a liNhlV'j r~lI1I1iijJjn ,tjclmipa'IJl'ld Jtlh!l:>!1!!'ll~CI~r,c)'n~ bQih~~ IU ~If~hl!(Yh;!!jfe;!!llI1l!1~h h~iiI~r mass,

R.. di!l~ S;OUlil diing'of th,€! .Mad !JI!'li!le'fjOS~<l.e PO,rrnh!l.tion Mar~; Eqll!li!lroriall[-.e!! or [) 'l. low· Derils,ity ,1LlJE!pnroits? ~R. WCl(ters et ,at Roo~r ~O!Jndln!J Qf C!IiIilJ[IOOr~1hjlL~ 01"1MiltS .w,g[l~'t$ !Ih~~(h~ ~(!fIl:i!in O! l!!1r,gl! ~L1hsurf~.oo 're-a'turemllh ~ow€lef1.SilY-ei~h« ,a IiIge volume or walter ice or ~~I!n~o~a!1j(ash. 'mo. 11261s,'Lilmoo. :ll1!H!U2 PLANf SCIIENCE Erl9irll~'e~ij;IfI'Q Modifiei!J 1St To(l;.]nlim CO!JIIIIJter I nSI!;ct i~!!'5istalfl~e M. 5o.bjj'mn. .L Pa.r:rJO·i.6plU, 1 t.6pez" L Gomt'4 B. E. ii1'bfi~htn!~ A.. 8tGVO Bt~.O.I!!iFl,a lflii1turr,ilil iln§,e(I~IC~,~'Bng~fil;f!i!reclilm.tD lpi<ll'ilts, ,alil 00 motlillied ID rnrl1l'((Jm,~
illlSll!d ~~~~1i!1 by~onmlf]J!J d~l1IIl;gln!l pD~'~~ p@n~ lindQJI~l'lIdm'lllly n(Q 10

lO.U261scieiilce.ltc490M
PHVSICS Go·h~rE!m (Ci~nilil ,~~ Q! Si!ii9~~IE~octroii!S,iill, wiI:~ 111Jectri(Fields K. C. liJoWo.c,<,. F.. :fl. L K,op/JfM, 'Yu. V.Nomro~ L. M K. Vonde:f.S:ypen The5p~n, Sc1ateof a S'lllg~e elecl~trI on a IigLianltuffIlI da~,•.aFl .be liIlIa.n~ptlIlSl~edby <iw,p!ficalliim ill a IDeall ele~lii~.lie-llt im,pro'lim.g ~h e e:ilnIrG~ (if iili'ijjll~.i'~11e [lot!!:

am it~!ilorliTIli!l

Pi~RS!l?l:ali,V~:The IlPtJllverOif the' ~iul'iliid ~ J.MoGIf' cmd K. J. ArrilktJmtJ'r

GEOLOGY l[i~fII!rnl@'rI~ 01111l.''Iles.tlg@ 'DWEia~·.s 1)ldl@:s,tO!j!Iil]olit:@;;

EOOlOGY

746

A.Po Ndooun and C. It L Fffend fuu tiMl m. f'MI1~rrif!JI,emmt.rJrwmilfr:Jm'mWt.JfI!31Bl5!~

51114 ~(

'~illllfmlle!i!t (I!1!~AVes.t!,ge ,[If iEaflllb'.s ()ldle:stOph~oUite" 1W.8. HlJ'milrr:m

fl1U

Vlildli!(I Ci'!rn,@i~a,S ~nWU~iBl 765 C i?rJtl,. l A. B{uff, A. A. S. W:err.AK~r:€{llik .M,fnfailun ~ed video ,(.a'lil1Ul!l'i3l~I't.i!rnes.~d IaIlliHcI Ntl'W C'a![e,d'oill~aln CmL!.i~i ~ItVI!.l'~~<Il:tnI!'!' oil~1iI uU! IiMgs. as JiJols in thi2!lf IIIMurtl~ Ih:!llOO:~ilt

~~s

r~xtor WiViI~ scimremog.rNgfqiilwflieflrlfjnV31SI28

il:l1l "A, ~s,1:iige

51fl41Jfi

'!kmo~$1ii! til (omml!l!ll:ts IOldll!:st: Op!h!ili~~i11l!:".

of l1:arthl'S

PHYSIICS QUIi'UilU!.1Trn S:@~I'IIiI1MIlIIllSl!!IatJJ:Ii Slamrnn Hglt@

766

H. Ftlrnet ,~'I:al, luU ten m ~;J1I: f(if!1lremog.fI!'!IIc¢/[r:UllmrJjiJlV.318;i5i1511'4~e

W'8~rus .M •. {,(onig et OIl.

QU!!!l'IIlulirn

R'EV'IIIEW
MOLECULAR i81:m.oGY

A j!l:mdictQtl, oo'O'Q:[ ~tam or 1I11<1itr!r 111: !l'ilil~[lh .. ~pilll-illidlutj~d nm:ll:nt rro~~ ocr!llss.ani~~ui!.l"'Min, ~h~ i3fu1~9[{! of,jJ rn!ill!]ml!li(lil!~d ~ defmm~!!r .. Wd in 81 dOP8i!:1lhiin ~Hm"
>~ Ed.[JlotJ'Dl P. 11 S; hrs~~r:!iv.,p. 758

The'IP~wi·pillllNAPa~hw'a.y ~'rovidie!> AdaJptive an [)'efe~se ~111 the iriamslPoso.1II .Arms: Race! A. A.A'fOIViI1., G. 1. n~/lflO~ 1, BrearledJI;'

'761

NEl.lROS C!i E.NCE

77,2

FQrtlim'b ~,en eratfon, ~i1! newts rGQ,!lIi~~ ~m~,!a,nt regeneration con or lh,e nei'i'e, a n(l(t.55ily ~I;]jat calli be circulm'i'erlil~ by ap~lical~ionl or al5il1g~e protein, mAG ..
;';>0

E/Juanal P- 'H;

PI!fIP~[.tirl!J. Hil fl

,R.EPOR'TS
A5:rI'lO!NOMY M~~I~i!i~oWlG IFI:ai(il]O BiJr$:to~ IEmtlgfll .];(till: ,origin II R.{o;rl'merelhIL, A. r<ipid andl powt!rf I!ll bUIr5t oill'iiltlio Iffl!:ill!~ i:sl()u.ntlHu\Ougl;i<lfil

A 'Bright

TIl

!!IfI!.u .. ~.~i~ !)f ~!!I djo

:>:>

~rdl!Wall PI!.!Is¥ .(Ja!a, ~£!ge~!i'i'f! (Ii ~ n~w di::lss @I

Ibu:rs~" perh~s f!!QITl .a,~~,per!f!1Jv~. Perope<rr Ive p. 75'1

759 &.17"
705

Science.
R:EPOIRT.S, CONTiNUED ...
AlP ru ED f IHYSICS If!lJajii,M(:1ll1eWrictioi'l 'Valned '!:i!li' I~o,tn,p;k $hiAj'i'1,g i;lf S,urFa(e' 'Vijib"atiornaW Fi~~qIUE!fhd~'5 R. J. Cctrn7arO et ~t 5uifralc~, n1U;~~dirn:~ln9il!shiltiofil.

CONTENTS

7'sa

MEDI:CIINE Men/lin ((il'jtm~ G,r,i)!iYth l~.anL':fE1atl1o( ,C!~: p·(elt in IPregfl<iiiit MiJeeai'ld IPmili'tCi1~,l(lie',st~~CiJiial~ialfuil1!tes D S. K. Ka('I1ik '~1:at . ASlliKly ar mice~den~ifiua Iprole111'lllatni:aYlrr:liil!~riIJnO!lC!n tn 9eslalioiil!iltli'ali;e~~, ill (omlflit) iii eii;Frip~iGilioii O!I~regiianLif.
;>o=>

806

ME!Uiiitl!!~

CnoogiRg !he surfate lermimlllof1 or OJ! diamond 'Of ,silicon sud'ace Jrnm lfI)J1d'r"O~ to ~e.Ul~i'ijj m lower~ Iliherib~al.i\)i'il~lF8q,UI~tJ ill~ltie f fJi

M. .5. (fum, Gild M. r. Wblre

~d ~itm(

C~EMISI~Y A Pftl,iJi mb'~¥S@i~.emive J\liglilatJ1c C~H 0.0 d:a.ti·en IRll"tIdii![I1i11 ~tlr wlrnJpiJE!X MohmI!lLeS~IiI:the~s

~'IiI

J/DQ'

p. 72~,

7'83

S'rfSTIEMS BIICllDGY ONie:medl PhoSi~hor;yl.a:tiolf1G01Jiem~ O~il[ti'lltion

ofa

809

.!\ ~,ynthI!l:Knit[tlg ~nl=oo!l1dililated' miil m~iM~sl iClin~:titJit(! o~idatiiJ.n ~ Cilfil

>::> P'eJ'1per!'w~

l.iuee-Pfot!l!in Cirt:adian (llJ;~1( 111'. J. Ru.est e<t. ;a,L

liirl(! qrclill!)oi

(--il bDllidsiDl m~n,~dirf~~ol e. 7.56

~a.!'llp~~x (lrgJ~k

ma~i[l!!tes..

CiHEMi'STIilY 4.[a!~,SU',ilJti:zatiolill (IffliililildUon1'll S·tmdulrre5i IiII l~ha'Se 1rr:allS/ri(lrmatii;lllilS> by ~teari(llrlDiffrPlcti~lil.

788

th~e~ p'rGl.@iDlrn.rnp,(j:n~nl!S '~[iII111p,ris.!l1lg!h1i! (~r·[Mi.:Iifi dli)~k irrlcyall!,obO!d,~i!i!is d liiven b~'i! I):m.e.m ,~f~e!!lY~rn~i.;!~ ~I:iQsphoO'li!1:~CI!lIhat tim be deS(fIlbed fTlal!hem!i!tlc<!I~. t ~~ hrilJen~'''' 751
IMtMU'N

0 LOGY

R' Bourn, D',~S.Yon:q,A. I{ Zew,(,lil E~c:!ml,n dli~'~!'!liCl£Onre'O'e-a'lsIhe r,emto~ec;o:nd in, vana:!ium :ditO\!;ide·,
:-=" PfHfJff.ti~

~ocat !lJtO'mk rm:olio!il aoo pioos'ocoooi lal~ice:5h,.ea!r ii1!jn ng lheliilsuliitoHo-me~l!Illriliiuiiliolil

p. 7.5.5.

EVOLUTION MIJ~'e:(ullair ,a.:lfi,a Gelliolflll~c Oatilll'dmtiry tliHi! (lO'.ses,t thri llig Re~abllveof l[J,rji1flMes

Varr~.a!ri:(llii! ml),U R~Sil~t,a~ imd IC~ 812 T~lerali!ceto IlIlfe,cti:Cll!IS I[)ffiseases il1l A~imals L Rooef;g. 01 Sim. A F; Rrtod InB,dl1itlQI1I to d®telowiin!!l mslitan!~~I!D' parasite- in recliolfl.. i!llj:(i]: (alii @'I,I'OiVl!!'tooolfl'8tl1 maia riel parasil,~ hy lilfllltinl9 U'I@ tlama'ge (8IUiStt!

IJ'ise!iltaog U'fHJ 6€!1iIrtk

7'92

Df their

prt!S@filli?

CELL SIGNAUNG

}:.E JO'IJef;ila el 1Ii1. Co;mp,atiisoin or 9~noli1i'l~s~qu~IiI()@S Irnma

!'i:!1i;'!!,lves.. @r 11!~~t~5.

v.liri.~lyiilfs~C(il'!S. sJi,ow:llJll~~ Ih~iIlilIJLlgQ~.tO'lfLyiii91~lri1Il!I~~~.~Ii: th~,[losi!St lwinf,l i:I!:'

t:

D:EVElCl PMElf\lT:AL B IOlDBV A Gellil'e!ltlJegju.lamry N:eMCi.ulkS.ubdr(u~1: ll'n'!J'eS iii 7\94 IDYfla.llilf,:c:1~,[lttenilO!f Gene iE):lpre!5$hli!il. Smitb, C rheo.rJ:oris,f. H.. {)olfimot1 The rirrlgl or ,glen!!~J;prreS$i)on~ ..~~s\!,Ieeps .U.lOSSsE',aw~hir1 embfY!ls is (on~roned I:!y iii regulatory [Icuil~! hal gel'le!'aJles al wilile ,of a C~Mij\a~CO:f\l. r'OIIQ!,!j;~9 tJ.ya, wil1l\!1! ,of re;pre~l>jI)n...
MOLEOULAR

TAR!" .Am:jl~.tIJry Sulbulnits :~wukh .#lMPI'! Rempmlrr 815 .#i;IIlMg~)IiJ,imint>e IPamil.l ..Ag:onis,~ ./{,Mmaz,. R. M. Stll'tlu.d,; R. A. !i1im.lt F..A. :ffuy.> It quillNl(l;~il'i!l'dll[jne 9!lu~arn!alh!' r~~p~or i!rl~go!1liM~CiOme":i; !ili!'!1 <!~O!l!i:!t W~Q ~hil! ~ecepl_.or <lc:q,ui~~ <11'1 e;;tr<! su bunil:, ,~a~pUng c:h<!nges,jn IC~.a!1ld.~ndfn!l 00 OPI~ [n'9i,of 'Ine cl1 iii nnel,

ilieiomeric IRJe:pea~-(o(lilWi1lf1i
C M. Alluii~ et al,

BiOLOGY

1Il9 RNA. arid R!NA. S'Ur\lie!:IU~alll(e Foctor) ,at Mi1immil[~nI ChHlrnJosom.e

798 IEllilels

lin lfi1i1i11lrIrJills, R.NAis. tramcri~1Jl Jrnm repetillive OINiAM '~Eleoo·~ ~d diI romosOml!!~ OI1d~ <I!lo:f'l[l i~h ()~h @r reg:u!i1I.ory Elmroins., is< w in C:(I.rPQI'8!'e(i locO!l~Y in'iIJ'sHl!!lI'Iredchr()rn~ilin;
PLANT S CIEINCE

A Hig:n-Re~o~:9I:Jio.ra IRoo! $p:atiomm;PDratM",lp liJomililant Il:xpte,~~oli!l!i!at:lier~'!O

S;

Re\/e~~. .

.sm

M',. Brody

e~a~,

754 ,&.772

I'I!~f('~~~.Q!~~m.MlQ#fr,· ~~'\!'e!opi'!!n!il ~WOi#i g~nes .~~ e~p~mcliln com,plex Ipa!:lemHnl'lll1ai\!e Inol, bel!ril lD'Fev10'U5l~ <lp',pa~ent.

,~I;!PIUt~!'!'~!!(l!!-~11il;

A!)y' ..... N!~1N G ~~ I ENC:iE. Ui!!\,!IN{i

,~O(: 1ElY

'r.>i' lIoo~oJO_MMS~I.il!liIj l!t1l~ ""I!i''IIMIi i!te~ f!iiW.Iii.uIlt~I.!i,D(.~i~' ~... .. lilol.bIW 1Jdi ~~iOJtoIjUi!>nlil~, ~84e:1~D' ",W .. Iji~I"". DC, ",,~.~MI(iOoiIl !"""11Ig·~I1,~ ~hi'O fl'Fo!i .... 11m' br III_ i!m""'~.,~_brl", .,lh.Jo!..."_,,, r ~·!llil;_'I1I. ~tl;~ltti!lWI",i; .•"llIiI«<1 ... .JoiOii ... r'IJ,;,1I.iU& lib....,;;I1<. ~r.I1oli!1I1iL"'''''bml1~.ii:!i~!,<ihiiibn;,;,ln~'''''''r ~jj~ '~:i'~,~~ ~ ~i:"!~brl!. ~Fi:!~ t1~~i,!i:!~~·Ii~~~!f~i'i'!.5\1,~H '~r.~ f,1;ii'!(~:.'II~~gt!i~~LI\I!Ii~~ C!!~~I~r~t !li';,IiD <Cl1tWJ!ilni!! rJl••mlil.d<'l.i:ttM'1~i!l.IlM.llIiiI'i'l,;.IIIltI\lil,;llIdm. ~~; .,d.fmmul.OiIl5 "" ,"",",~,C.,.ojI!l".rjj"'M'liI·G6I ."'!L!"f ~ 'l\lut'i!" 1)5,] .:!2H BBlll_ 'ij!l~,,~! lIo!l,!'iJ'._1 No_ ~P~~!ii.~" t. !lIl!'N~E ~p, !'tr~1 ~~. ~t!!iIloiil!<'.e.-$IoJ !iIi.iH, l'rIi'iI:01!

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~1I!o~OI~!I!1~ ~;Io!,~~~.,~'W~I·~kO.!n!. j;!l!lii!!'. P!II:tI!iIllIU:~iO!l~.~~c!,l(/ij'!!lI~UiI!U .o.I<l<" u.1,·i'!!1IlI1"~~" C ... D M(liI!I'-,!:I~.~~!!Ilo~ !Io<H..",.l"'f'oI.:i "I!:..J .. '~""'"poliD;!O.; ,,,iIEIi "'''''l"o;;j.,'''udooo·lUitIlooo~ !phoI .. ~PI' ... ~o!~'" 1"""",01,., pors",..j use u..r .... <lrt!J",_ '""lr.;j!l1~ .. ~Iilolli. ~~ oM·".,i!i!i!o'il ~ !~.~[I!!mi1l'(j'~~ ~''''''''j; ~ ~~ m~n,..._ '11i1i_'!1~""~~ ~H""'!(oJF-i.~_ ~ilJfo::mf~m;!~~ ~Ifui!~~~, .. ~I#~~ ~iI!! ~1M!l'IPf'~~!!!:! f'!'i~.tI~ bile( ;l;l;l R""_dlbl ..... v'".,.....~i9,Zl,·IooIi!lBilHlt.oIbI.t>:i.,brf<lioo1C1i'" OOM-!til~_51.M:.'II.·~li<>odl" iI.Ri<'Ii:I.ot·'.~.!I~a',V,l\<iJW!·_. .. ,..,.,..J"!'ffioliood "do",_ .

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707

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WVl'w .•sciten Ci€

magi ,org

SCIEN CiEINIOW
'I'fI'M.$cieI1Gll'IlDIIl',org

DAllY NEW5 (OVERAGE

nbi!ta uS Get TIii'~f ,B~cod IF'~CMl'ig' S~lIdy iIe'!lelals 00w lhlgilil-.altiilllld'e ·i:MeUe;['S roiiJ1Ip oo5ate

'lor [ado::nf O)l/9.erD.

E(i~IlWii:C (otJlple Rieveaisa Starry'Se-we.t MifJW modei t'~~~iftl!i, \!tiySmriu~alooits rompiimliOOl!n,ave jliJch ,Sri e/cmgatf'ij, ol'irnt Se.il;, ltlhJil'lim s,ilIllild VideQlt'lpe: :S1i'fi:~mlli1g' ,an a geil1eil1l, l1leU[!(m5, Gain alter wleimaro,des,"

SO EiN'CE CAIRIE:ERS
wjjl;!;\1,:sd~ncecare.m.mg
CAREER JlESDUl!!m FOR SGENTiSI5

:sexual behavior.

dl Riel;c>g,milJl!IJ m j. :9...loaini. A. EMid~aels: 'ThE:O'IiiJlioo~$a:dlrisllffiS;~lrdl~;~ on m~!iI<ligllilg' PLJbli(~j~!:lIll~ ~n;d c~.Jl:iom!S; p~ 1 !if 3.

S. ?Jlftr.(Jfl, P; Bt1~(Jm~ it f... Belt

US:: ,M~ximlili:iifl'g ~rllldil!l'rnvity'arl

GlORA.l: In Per:5.'On:-l1~e ruUrr,[lLoliIgi"'D,i~tilllu,e lijlJe:o.t ,L .rlell,f1~{}!:Jaus~fl InIUiI~' Ur~fIrI, ~lnew:~m~sof ~1l:P;,O\il~1P~~pi!iCli!'!~$,i1I}(if!lfI~iSl! ttl~ wl1i~t g biqrcl~ ~md'l!I~noo 1~(I~ t~dllll;!l··1ltItD@yt.;;I~rt!f!tf;
!E!Y I1!:O ~iE:: Somletiunlng "5 Cooking E. ?ain (.;iIl:.'lrlnta pn;SI!~~1ld J ~1I!a 1!iloura onb $d~lfIa: and! (oot;ing in lh~r ~tudv Qf 'fiIlo~eclJlar'Q~strrolilcmw:.

SCI ENOE'S Sl"IKIE

wmI.5t~e.,{)[g SIGf>,IJlL mA~5Dl.!cnON

ltll!Jl1!:OfiiE~ Frolllli! tilil,e Ar,!C~i\!'~Fmlllil

Crul~(i~~f!~SS

Cinspillle'ss

KNOwLEDGE ENlJiRQNMEfJJf

R. HO!1mollt
CiliIliSCielil(i? 1i!(i!1i!i1 j]i5~r,o:nollilcs~Iil t~~if qlJl~tl'!l.r g

illEIf,t5:PcClrIVic;: N e~,!Ir''O>tm:pih~I If:tlct{M~ <lind parii{ijmo 111' 5 i!j,filClilse--:lhe Icml1[!gelliloC:eofa N!ewIPlayelr? iwt fmue:f

tast(2, hii!!ffi,()I'IY.

fllldte:iflwc£

SOENCE ,ONIJINE FEAllJRE

TiHIE GONZ!O $ClliENTtSTiA. U!:'!!i!~~ FeiQIst Tile- s@icondl in sta[~m@nt iifith~s :stf!ri~s

SCI ENC EIPOiDCASi[

_
D!OIlllf!'ro!!dth~ 2: No\l'iem,i{e,r Stiie~re IP.odltas,tto he~" abollit ~ri!il'li3!t1!:s' dl)S"~st lti'!!iiing welati'.re ..

(in du.d1IlgaJflaUl:ii 0' :s'~]deslhow) Hlmm'e,liTWlr.1lte:~ tlhe 300th Dllfilihday or (<lr~Lilt:lnaem; •. W~O' 11I~:d the' fOlJlIlIdatiCl!il '[!(If modiE!rn foodSiril~l'I(e.
li~~,«f,i!rjtemgg_arf1!t'~,oo:~tJ&:1r:f.rj

oou n~ring p@S1i(id~'r,e!il:sti:1liilOe" '

IllIfi,der"Stillfl!(jing peanut ,dind mera, " iiil.ltrgi@'s, -

709'

EIOITE 10 B;¥ S,fE lU HlilURllEVAIN 0 iNiU l 5.2!U IF! MI O

Quantum Splin HlaU

!Effect Confirmed
(lhanJ~dc~rfi1e~s~~bjll:C!tedW

a iIT1agrl~!l.c ~,ad can tHe denec'le:d~!II,d j:lrodl~ce ,~ IHali "'Q~t"ge .;I'CI'OO~,aJ :;o;Illf'! ~ ~e.ollllf~ll'Iiflg the' d1!l:Irgi~cl (£I ~~'iE\ts ( to mov,e ~IiiII,W() dili'l'lfliilSiOiIiilS car. 91~iue' to 'l~e rise qilJ~IiIW I'IlI Ha~1 e-fJ~Ic:t, H!o!;l,l~!i!'ef, Idhal~ge !C'!'iuiers a~~D~D,sse:s!>p'in, ,ilInd recent 'l~eDreHc.aILwork s ~!1dkgltes ~hillt~:il'ls .;a ~ be ,aUect~d~va \I'(I~~l;Ige b]i31l and gM ri~bill5:pin tillat~, eUiocUor !;alrll'i:ers (onfinNi tolwo' d~melilsian!>. l~ij,n'igl,ehd .. l~p. 6,6, 7 pll:lW:i~~5dCl.lillnne ,20 S~pteliT1l~r; see l~e P~r,sp'et:~ tlve by ~alg!lIo:l'Ml~!performed tr'illl'I!>pmt 1'I'I~.asmement~(m HlgTet(IHg~Crl)TI1 C:P1JliIll1lum-'W@lmtru(-' ~ rurr!Et:lj i'ln di pre:8ent :~igl1f1rtu PEl'S the QI!lI flliIlum or spn n HidU, @ifhl,CI:.

have liIlJaJd!ejJrog,re>s taWEllrd t!n~:5 gO<l.I.by <lPI~I.ying tilTll.~·rll~I.'!,!\ec:lB[edmrll d'iffrlldiollil 1i.o 11 Vlirjlj ~1I111lplein the midst af ilt~tJr anr5~Orlil1lati0Ii1.Th e W'!eu.. IOOn~ilileIlIP'roo]r1gl dl:!pth 1II1ld Ihig'n sigllmi!lll-to·I'I(I~fIe' rrtHin jIilermifioo' .rr@':5IJi~UJIJi(m(Df'~()(oil~ .Jlollli(. lliIot:l!On. as wllil ss !ti,e :!loower i31ll1cl ~ong'l¥f I~ ang'~ !On~@'l of ~"ttIC~he"~c,,er,3, ~J]iiJ1@' scale' rglif!5[I]lfIIg [irorn ... 1 s HI 100 I!JlCOiS@~(md~.

the f!i1 (i!~on 'ron!~of diamolild an dls:m~:1fI 5u:rfacl€S that li\iefeleIT!lifialed~t~~ €ith.e'rH or D atoms. 1Ms $lib$liM.iorl 'i:l~i:il!!lge~ Lhevib:rg:ti!!)ii1i1!~frequefln::y by " f,i3JttoJ!; between '1.315 :;lInd :11.40,

3ndAFM eil:ll'e.ff~e!il1S fe'\lt'al[.e(j Iha'l tie she~~ streng ths rdroill'pie,d :ror bath SJl!lrfac:e'5, b~ f;:!l!rJ.or~o~ 1,,2j), andl 1.30, iJ'e~pedilieLy, upei!lillEl ~l.Ih~ti~lIilioln.
A InilO'de!~ing ~tlJdy' ~iLJ~Hl:e-stl> la,t~he ~I~r' fi"E~· U qy,~nt;yo~ ~t.,~ deLI1.eri um -:S'i!I bs~itutl1,d boml Illw,er:> the IF alt. w~kh :~ll1e~:k ,energlY GlIi! beale faniverl!ed illiia 'IIibrartnoIili5.

Fast and low

ASitr~~hys;kal~tp'lOs~:Of!S G! ~ reb~@se h~gie' bYr~$ 'of lenerg-yl!ll~l~i;wl be spied at dHferen't \11~~ ~elilgtih~, womih e rad~(I band IJ,~ ~o g,amrma. rays,
5(~Ui~llllg pi!lh:lIr su:~vey data, LQr~lirl;l':rd'.(lII',. (p. 7'71, ~u'~ln:'lhed olliiil,1ne :2 JSep~flil1ib e,r; iee ff1e Pe~~peLl.t\le'ltny' Bowe'~1 '>palted <I. fli'!W abrupt. ~msl: l~<lt lemiUed very pow~rmu~ riidiowlIlJ'es ~m.iU:5~ 5 miLli&e!i:Olilr:k liI;J,e110wfrequelllqr a,!ild ~a:clkof rep·' IlItil1iOill o,r the l!!V!ent ~lmgJg!e.s;tth:i31 tJiJe :SDurce ti:~ be)lolmd our OMl 'Galaxy;, vdlrich woulld make it !II'ImepCiwe-;rl'iUi. and h.riiBf lliarn (JIIIlIHrad~o'traDil:sl1ml5 klilO,wlmiilm o~rM~llkyWilY" Bec.alu~~ ilihis Hash tll~.e~y~rniilliil;ned! JrolfI1la s~l1g~ {ata'5trnph~c ~wmri.fi!IU:h as ,a, ~,p(j'M~vaar 1hC::~lfIal liIlI~rg~l!iIg('jr li~ati1;l]i5tJ(,cbjem,.s.]mflar

Piwi and the' ,ArgonalJt'es

All the h e811'i1of IIfl.N!A. ~ I1lerl'€reiIilCIE! ie t~e Argla .. ~ Ila Im~!!'(Ago) l~ro~l!hlJS;. wIl irh bilild ~mlllUin~~er'ing IRfillA. Clirm,kroRNP! ,f1lnd SOl,oonslgl!1i the- talr~ g@ted messenger RINAs to ~lheir 'ri:ne--si~i:!l1t)edlor destroyed. ThE! ,i!!.~olsll:.!pedaJllfIily CDiflsi,st~Gf MD eiJ()I~li!t!lontlnly re!~a:~:ed9r()~p.s, tJi'i.~ Ago dad ~ ,a!fid the f'iwi (lade'., i1!1iI d Ar,!1!Il!!!i!et {po 7 ~,e:v~iew the f'y~ ctiOil'l oflh is ItaHer gloo!.!~.lhe e1J!J;~ll!t~ioJ1" allY apiPeiJ~af]Ql air Pijm prolehlis ~s oowet.n~

Ira nsifions
dil~!i!iI dil'll~jdf
(\liOl}

Hectrons Tracing

m.

c,l}

I~hO~~iflducedtfa !il!sit,iQIlS In so!lids su:c:ha:s vana"

than: WfI]i€rt

wlththe emerge~(:eof

splocn a~i~ed germcelb 1~

f'rolfl'iii!il$lI;ItgOO,~s tc
<l!

!'Il,eta ~ have 'beel'l

til studied by i!! ra!1lgi~ ; ~f .~lPectJro$C)opiic ;;.;-m,~tjlmd1~i. Hlow'"'I li el!,l~r, tJhe rJ.mde'lty:.. , ~ ~tno~ irealrr an g~
'!':

.-

bdgh~bl.lrs.1:s,o(dd ~r(]ve to b@'I!.aiLlaIM!

p!iQb~ air til@- diistalf!t
Ulif!ij~ili'S@,.

mml5C8lnJin'll0llve

A Charnge-U p for SLiders

C,{!fiI\i'elill:

animclLs, anid, nl!ldeed., Piwi protelns are ~eqJl!.lilredi forr :gerrm ce~~~, d1e'J,i'e~opme,iilt They arr,e.also ,oon ~ ~~nts fIor- ~ populLM,101'1 of re!,)~ni~lyis!l:!O'!Jered d slma~lRNAs .• 'Pi!N~ 'imlt.eracting (pi)RINlAs" r;he 14LwiIp'iRNA. p<l~hw1l1t 'ril!mdkllrn~a!i[lheirr~ilIlb~e and QiCiapti'ile ~~teilllil tID pwtem. tliii egle r!i11itili1egenoli11ie' hom palras-itk nrm:I~~k<l.ad!>.

~ mo~ki,1iI 131[0 n9

:i: s ever.a:L dim~rel1lt

~ (Oma~llllltES. illilids'll~he deepest umJerrs,1:.c.nding ls IUrely to GlOme '[]rolillitochliliqJILR'_5 ~~lIt lfIl.olm~tor ; an orlht5~ IIti lJI!.',ecl1ll ~n1iliiS~1ItiumtfllllIDUJsLy. IBilIilm et ~ ,111.(p, 7!3B; s~, the f'ers:pel(tilv!1 by Call1l'ilUen)

ImL bklion? Cilmllli,1I1r3' ~. aE•. (p., 78Q) used an a:!tollflk '[orne mirrescepe (AfM) tip t'O rneasare

flr~,ct~on betwe,eo~~i,di!'llg sti!Ff(lICell Cil!!!'J: tr~iil5!~Micmeiter9,~ll!lltOll;ribralion~l exdt;:!ltiO;f]~~ but ~owhat ~¥~erIitdoes :!.he 1iI.. ttl!Ueo~~he viilbrationi31111il1i0'desmn~ro~.he a.li~t ily 'Clr ,;31 SLIda.(!e layerrto absorb en.ergv ;:!Ill!Id'COIlii-

Of life and limb

lfuJellliJilijt.y (lir .. mp~ibi[Jn, tl(llregel!illlrll~e: <I iii 1lilfl1lputtl~ed ,Umb u:pre5!ent'5, ,111 ~V~~OpliTl.mtil~ d Jlex]bihLy '~argJety t[l$l fm hUlliflal!1i5. The n~ge1il!1[al"'

711

t.lkm p,mcesg,in ,[llmp,hlIDi1llITl'o; d1epend5Qnin~iffaLl:iQnJs with the n enve 5l:lpply, IKulliIl,'Ir ,!lit at., '~p'. 1'7 2; see '!ih,e Pef:Si~ednve by Stal clUm) hillve IIlIowid~ntilliMa seue1.ifrl pfO~enln 9 rOlNth '[,adem expn'!5riediin~liIe
II1INve"l· ami ~piderlilili!>dr !I1lem5 dlllrriDilQjlim b [eQ,ene'r,ati(m lli,.1 wl~l!m the l1erve sl.lpp~,y is; Hl'fIIiIj,W!,d. ( Galnl Sef'llle

tit] rulPpont rege.!lIBratiolil

e~~f1

Dyn a m~c Develo p menta l. Gene lRe'gu lation

IGf<lie !ll9lj'~Mc'ry ifu~bljiDrk$ ,oon~!roi,m'~1:azoamJ de-ve~opiiTiE!~M and ce:h!!liJiillil'le wihidi 1Jf,aln'scription fai!JI:or,s \'M]~l.reguilare ii\\hidll regl.l~Mory !get;( e.s. Hlowevet,(ieve~.oiPllllri,~nti~ ili!cyna rrif:t:: ~roCl!',5:St~ al is d:liivelii ltiy co:ntifll!!o'l.!s c:tI aimge il'lt~llll~ snd $va C~. Smilh! ,!!'t aJ. (p. 794) flow :slh'(!Iij\ililow"lliI!~~,~Cfk ~~ wrcYlit centools iii! d~CILdg'~pi1l1t~M regi!!l;1!to~ gie-f!;~ e;l;IJ'J~.ssign~'Ii!~t;!S\l,!e~p,s o!l!!tward 'ffiromlthe~~:eta~ ~I.Il: of the

or

:seillilludlilhl embryoaJ!td exa:irilgl!Ji$he~i~ owm O]C;livilyinl th~ mor'ecen~!r" I,~ lens to ~s1aJll~ish
Inegl!~a1my

!oil

pattern or 'gel:'!e·expres;s~orl,

~!laJmi'

SoUl th~ SL':.;!ndelltia (!tree~hre\~II,!JiIl:l Dem!'lilopteuaJ a

I~CCl!~Mg:~~ CI:!'f~:iili1!'Jjle,liIiilJlus) ~ <I've been p.mpaS!~d!to

~ep:I'E'~!eflitth~ dose~t re~aI~1ii;1~S; p,rinll~te5:,A ·of Ilargl~!;f:ale £len.CkIil1i~)C: se.~UNl'oe :a ~i!JliUl'liI~:nt lP,e~'rormed b1y ]lImeel!a1 ,ei~' '!!J. 1'92) nO!i\l 'jl:lgg:~s1:~ ~lhat mlu!Qos are Une' dosesl Uving re~atll1i'e of pllimallie!>. Fu ~:hewm ore, tlhe origl1111of treesilrrE.'MIs <It tih'e (re1acoolJIs-ier:1:iillry OOUlndiillry flildf:cates Hlillt '~Ih~Ipri mates probililMy eJ;Io~';IIeda~;:[I1]l1lf'!lIIh;~n 11iI1Iirlyother mfll1illililflU1a,n nn~iirg(!].di'!lllrs~ioo.

m.

A,n End in ttselt

re~oIiIiIlue~,!IJ!h]ch ,~p t~'elend~·(]!ff ~ulli:!fLry(JtiiJ;; U(lmO~OIflflll':!i, ~oi~V!@th~"md replitaLiorl~ I~rol)~m a ~ n dl prIWCilinit ~jhl~C~!~~ frowllI mls'taJkingth@ If! ~d's ~or' DNA dililM1iIgle •."i'eioillll eres ht~¥@ Qiffl:eralllyllileen '!ltHni~ to be tram) s-ci1iptiOlf!any ]~ e.rt A.:uilti'!i!!l:'," (11. (p, 79:8, pi!! bllshedl ofiltli1€l' 4, rOGt~lbe;r) j;!()iiI! 's:h~w ti!l,~t,i!il a ~a!1ge g~,hl!!!f!iI,gjfll~f]:d mdellt c'elb, 'll~()me~e:li are i~~gcUr,~f!iscribedj~wt~gmeric: f~lpeg.l cO:liltaliliing RIN#k'S,whkh a~SiDciat.e w~tlh thele~lClmere he'te.r(ldhr()rn.atJllfl. Uis as,'S(lda:t'1QI1i ·~.liiIWdli!l.a:t~d ~

nt

I~'y"~eb:NiJ1el~e"asso,ij:;!~edproteif!s, whk~ a~'e aho nUi!ked With ~he!l!(;!!1lserr!$e~medliated dec,ary RINA s yrVei~~Clililt:lep~~hw.a:y.

the'irum3"'~ll1g IP,~v~ia~ IlOJllka~ d1ern,i:I:nd~ p~i:I(ed (1m! ~'e IrnICiltnelr by the gmlMiIlIQ mE!tus. lin.e!liIlIole{ll!l[lf Irne,cih[lnislll'l'S (Cultromn.g !lhi~ physl.{llngit:JI~. resp~niSe, witlie~ he~~~ p,re¥e!f!.tltie d~!oI"Mpment a:~"gest:ltio.lila~ d~'ahetes," nlil thE! nil atn.Br,. i1Ja\l'e beelll! 11mdear. Stud1ililigl r!'lOU se' m;[)de~!>" KtImik. etaJ', (p, !illi6~ Sit! e 'the lIl!ew.~ .~Lory by IGo.liizilli) 1I10W .5~owlbt mllffili iii, tI p:rotein l~reviolJl!iLyic:l~nitified ii'!5an eir'ldocr'ilille'tiJm 01' slJpprrllBsor a C1Id '~lran~cnip1ilonal.IreglJ~[ltIlr, ]lIl!tiilbits :tihe!lrOWln ofislel p rn,~15dltiring pmeg.lilt1my" Tirrantsgenk explr'imiiol1 of menrin ]iIII lliI[fjtema~. p (ell'5lprevtllilled blet. e\l:!~ilIllls.iollilIliI,dc.aJlj$edlhe mice 10 de:ve!rop5i~e,[a,llhaUt~ m.[fjr~, feBl~1J of g;~till'tiiomd diii'!iJeJill'lO. eIlil~'1n 1Iipp~ar'Sto b~ maintain ed allow Le'll\~lllllli1n:5l~ts;through fe:s M ~'tiJ'fIoea.ctio,n"i of til~ip![egni:llmy-'Ci5~o{n;ated h!Orli1liOne prol.KI:iIlll.
l!i:

Molec.ul[a!F Culprit in Gestational Diabetes: [Dming pregn.am:y. IliIlla~~ma;l 8iflruieatic i~let p nl~~~ expi3lrtdm arcolmlilflodate ~

""

~ Genetic Var~ation for Tolerance ~

I~I'Ii9rniiflili31l~,.l~@'di~isti~aiOJl bl¥~~
::

~ ~ ~ ~
~

~
~

~iflilita~ '!'ii(m) Ie anirnifer.:ti·UiJl 'is: f~n~ly rnade-,"!lid ~h~~ is litU.~ u!1,d€~sttQ nding of 'dii Ii!i·imp,act 'ef~Q~~~,"r1C€lc:nth~ flvowlli!jrla!!i1d ec!~lQgyor a~i!il'ba!ls and their' paJlh~gef1,s.!R~b!l:rg,et l11. (p, S121'exp:lored t~~E\~a:n(e to g ma!lillna pa.ra!sjl~~ mic!e'. l~ki!'!~ Qiumia .i'!n(ji welg~t [oss; asm~~rures O!rlO~,~raill~~ ]Ui! Q raffll~l'e~Ir ouse ~iII m m.ains 11hilU;e~~hef I~edlijoe:d ~l1'i.~,as~t~ ' b!i.!rde!'f! (I~ m~~mi~edvi~ ~Hdijii! iii!glij'ifectioi'i., g gen elk ~,~i!; fo~ '~;Qiei~,gnIO;!W1l5' ~'e\!'~led,Mo~e~r, Irr5i;t9i~oe a!l!d~ollera~~e wNetrade,d ~nQ;g~iiil~t §ali!:h other I!\Ihen 'tI'e IPri re 'Ilt mOire agg!~es~i¥e iilin m~me OJ.liltroi o.f 'i Ii!llfedioll wa~ in,re.asinlg !l:~~l,~te~·i31l dalnilage, UIlJl5,. animQils;,;;lIre: 1110,\ g~'walf-S elilQlagled. il'!! ,evo~i,lUO,!'Ii;lJ'y~~rms ra(e'~" with ]!ilf'edio!Ji5,org:a,n]sms, afild it ~'l[Ild' be j'lJ~ a5pmdl,:u:tive trD breed IHv,~todk for di:5e<a;~etoJh;~ran(ea:s ~(J~ re5~I~tancelo' 'inmedion.

r~SilstilnC!!!

(pat~Q!gr:ll11fl Liliilil~~.atio'lidandl[ClL@f'aiIflC!l'l' l(dillmaglli

Ca~~ tQ,dEr':{ to put llh:e T aconl c .Mva~t6ge to, work for ~o'U!.

1.SGG.3ia:I!.G~49 www.,:t:ac::onic:.cDril:'llfadm.eL:s!cl
1

713

EDrT

R~AL

SCIIEN CE (OM I\MjIIN I(An 0 N I'5 ,A IH er rO~K

li:Ional(l~'m[II~d1~' ~s~h~ EtI~'or,]~l'iCn!~f S£i~Ii~. ~f

TH E

CiA-p~oriRg, lmO\vsc:i~ncejooma!i.:5ts ,iiild sdcmisrn CilIi'ifii'hd i1ev..\,I,fiy:s u~\wrldjj_g more effucl!i'!iG~y with g~e ~tl~M~~er~ Prngfam~~uchlls~bc AldQL.coQpolclll~;de:rshi~lfuHmv5:hip~1l:re:edlJ.H:;.uing: YO\lng~i:el~tis~ i':ibout hQii,'i'~Q m<'liw their wQf:kmore~tnd!el:st~ud!<'Ible tQ,Ole ffi>\tblic and to the mainsh!ca!.m mod~a. These1!ro >C()~lmol'!~itje:!'!.8e!)~~PO!ilJsc&~ohvo ~mp()ft:i1!!lt ch;:Lll.g(ls,. first,the sc]c:nUI:lr:;d!iscip:~i~~esf~ drilU!lg deeper i!U(l! the :ft~lC de:m~~8llf c¥eryth~ng ffOl!fl "tn:t()81~hcrl,c
pt1i~sii.(':s the: molccu]a:r basis ofc:cl~ s'u~~ding. Ac:1i[)nyrlil:s,mlld ot.ler :shortha!liid~lm;di.c:i~.aJ[,eused ttl! morn;; Ofil()ll ihan ever, ;;Ind (:von tl!ielidc:i1 ()rllesoon)~lpaperg a!f,C::;;ODctmnnesc;~lIengil1g" Se~!iild, sclenee ~nd ~edl1l!ioTogy ~re ~1'iCr'L:.'as:ilmglY :I:eh;;·v~nttc)pl~bliiC :pd~!CYjmJdUIl]~:$ those who speak fl)r : ; scienoe can be I,mdersroor;l, the(po~i.cy dt':Ci~om slnelike:ly W' be wmn!!!, S{I~~.ow' 'we dOJngS!t Sci{;!n~? frQlllrcad:~' sl;ln>'Cys~ dj:~t1~,iollS .Sire wi:I]] (lUll' BO!l.m of Re\"~ewilllgEdn:lors:.ami In),,'mRi] 'We. ge~ t]ae same ~: G~ iJ!ii ynlilr OpLntl)!'1 IM~ ......~.-....~ S~Ol)'. ~1f:lail.lgJl~<Ig;e sed ill H:.elPOl1S: nd Researeh AI.,tic,leo;; is !luft1cienUy Tl u a tedulIli.,oai. aad 30C<1:m,e ~~'D:atthey <Ire b~~o ill]l;der:staIli~ :evel) fbi[ those in related di:si::ip~m.es. In ,ooil'n,vc:rs;alIioJillIS <Ioont tW.s.PI:IJ!;JI.e:JiU, lbase Ilea:rd~le rO]]Q''I/¥~,ng: "1.1 d!Jes,l1I't have' to be like ~:is: ed itarspush ~:lm.\d to D.<I~:e -,. .umdlOif:S ~!IllnpiresS tliLC]I: :~aJ.l!iJ.u<uge too much" (Point tilkellil~but <Ii!]OIl,V:m:g extra :51]:101.00 tbil:' 01 arityin pa:pciIi It. makJes leess, roam il;van aib1,c tel' the newJi~m;dtinWl in pllperB. t11lld~e.s a1:f>O cost.) Qr:'ICan'tyou {lo,a oom:r jo!b ,ofte'ac:l1ing seme Of~11C$.oientiists t.OW[1.le in a mere accessible or 1.Jl!1i:dlen~t~nd01lib]~2 wa~f~" (Anot~,ergPQd poillilii~but edhonw!ho do tll:laIt sornerime!!filild they edit fur mo~c,cbrity\\ibi.~,elliuthorsin!iiSl: hlt they are sacrificurn.g PrG-ci:slOli1l111.Vtlid a:cCllrflCyn ~fi:j;e~!lr tih:at !lIco~~ib~ru]ty ~ prob~en'l!, OOea~!8~ i~ all lflyp2iopl(; MaLI or olillinl!!' 5IlIw!!)': these da}is: Each 5pee:iahy ha:::l:bcusOOI ii:! to, ~ point atwhi(lh even the M'i!W.sDelOCe Itbag ..crgt OC~4iP~i'!It~; noigl'ibo,ring of fi~~d8 hii),ii(i trouble 1ijiJ'!dtiv~t~ndi~'!g each ~i&q;fE!\35U f'I!!f Q~hC:fS' paiP'cr5:. We t~[!l!1;lc!:!ln:\\tdy lIU1~h;rti!l~kcWlS(l.1;': m~f!Sl!rc(> tha:tw'C=

s.;~DAVS.

I KN rOw

(I IFTWO

COM.M~TI H S

_L·_

'l(.-er~

t~l:ink:a![,e el~fut We]loororc eachissue~ h

\¥e

gather Ne\vs and EdJih')!rilal ;1:S1I~si:Q, ,consider \lI'~lich S

Ibrthco:m~iI'!g pf!~'jcrs 8hOliitid be ,f~cc~mp<'!!ded News Qf a..I\:npcctl'\il!;;. t]u;; ~a~l:Cr fw]iJ!idl by ~ pr~vid,es a 'CQ:llil~.t for, er lPo:ss~b!e e:x:~elliii[orns o~~nc\vl:i:ndtllgt; pub:~]shed ill 1:futesaJmiiieissue, We hope t:limlt~h~~ e~1(.lTa covcmge fmpiOOVf:S ,co.pl'ehe11lsion. 180mrun c:k:m."ItM!<IUo s;CII1~c 1lI:ndel'ly.i[~.g ~)mhk:m weneed to do sOlnclll.ri~~g mCII\(,': H!1l1lhiti!lIJ$, t£ne Accoruingly~ we :Ire :iTtlhi;SJting a new c~"'pedmeflt, begiimdlmg {In I!l'" 766i!lii. tlli.s issae; Each ReseaJfCli9JA:rtic~e pll'b1iShedlilil.is\.Veek mldillmllhe nexJtillVicisslJfS will. be preeeded by 3. Oll&pag.e "Authm:s' S1!IiIIl!lnalj"; all <IDCO!J[llt, wit.lnl one lfigllm .. of \Vha:titlln,e paper ~"eports sud whatits cancll]s:ions 3:00. Eac11,i1umm' wi~.~, have agreed to. sl1pply such an <I.coomll find IO let lJ.l'sinpmve iutSlllC cC.'tssi:bi]iUt)I fIInd d<l.rilty whel1e needed,. Our plan is f'l'lr s'lirnlma:[ies ofpBilPeI:g inpl.~J'sjmll sC]f:ncetnekls, to 00. reviC\!,.;edbyouirlire..s;cie(llices ,000iton. allil:d vice versa Thi,s el'!:peri ment will <I0cct both t~e Plr,~ version ofSGi·~ti .eand Sd,~fjoe, On[ ine .•]~i s fit c Emparmlill tor Qn~readers to, 111J1de,ust1:ll1d 'ilfu,ePUlil)O{se:.£ offhe di,ffer>ent ways in which we pn:·::;el,lt research papc:Po'lt£l i:m:prm1c underntaJii:dJing. The one-p ..~c summaryis inte~llded to! nmkc ck:!l.lr what: theitlive<iOt.i.garors did .. ~ow itW<li5 dene, wh<l.t t:liier:esll!ltwa8,s •. andits si:&>t!iJicfl]1ce. A P~f:spec:t~ve.a~ a]w.fI.y8. '!.vUIbe complemelm:ta~y~ pl!l:tting t~]e rlet,,[.ri::su[t V~l eontex t~ exp lori wg irs.impact; dril.'II'!'in,g in rel <,!,tedi,J]!:rorl1,liItlOofro:rn other st~di,es, <iiild asse S;S]ilg howit ,dH:lnge."l th~fi eld, Obvio~IS~~j"'i(; \~~~:t(l'[;"V'.aJ~W1!t(!lhc,tM.!,ooOOn(; t ofth~s e'XrerhWW!l'~ so 'il.te; in,,,,!l1(.lre~dorl';to look wi~ speei.lIW carnal ~lU·c; flf:M of t]];~se" i~th:iso ~SSU(l, and ~t those th<J,t '1!,iU follo,wfo'r~]];(llill!ext s()w!'1!] weeks, Gi'ile·~.ts::f,our opinio!'!,. either b)1 retl!irn~!'!,ga ~;l!tr"t{::yc<u4whic,h wUl hei~ ev{:t}' '~s!B~e ti],,~~ ~s,~ltlfii':i!lna:l"!e['l;,(l!l" b~ g(1Jliliii,goliillirlc 'I~ ~~,:>cie~~e;m!l!!;.or'j1:/sc:k:xti'ea$tlrvey h l"l,ll' fHI. Q1!I:t~1 :s~o:ri:quc$f:ion~lIlJi.lJe, We lo()kfonvam to ~~earimi,g&ol11.YQ~~
j

H)IIH D IBV GllIBIE'Rli CH:I'N AM'D JAKE VE:STON

fS"l'(~

{HOG"!"

(ognitiiv€! Homeostasls
mo hcmd two Opposed i,tiedl~in 'flll! mindatt:a'le Si3!IiIHlUrnJe dirt~mH I'Etai'liI t:hil!i!lbility t>IiJfiu:ncfmtlllJ lfilfls b@i!1iI hiiiUediJs:ff1e mark (l!~ nll'5,1I:
r

AI~,as,,ample wjdi!:mtl illJ~['GI.!b:i'~ tlil~t IfIiHI~th!;lm,il!rls· ii!liIeab!~,e: IIln,a MlW~il1l~1 ,aJlt~r th!dr artt:!t:udes :51(1' !l!SW 'bri!1l!il tlilii:!'!li!1lw linlli: with to h(lw th,ey Ihave be!l1a!v,ed.,i'lnd fh.Ii!'s to redlu(!£: UI,e ,dis'(;Qlrdalll:c:e b~l:1!'oiil!,e!11 hil!~~, ~Iif!f,a(t.thlffl~ le-q;l!!aL~lf\laLY~ it~s ,(A~ 13,. and C) ~

fCib! ~rgb!l~i'g~'i1 (~afidi!\loili kI also be U~f!:ly tIJ' 'f!:LiiCiltClJ state of ,CO~Inithl'e dis.'Solll a1Iil'oe-" wllrli (ill aln~!!5ii\1h!i!jIlJbE!'~i i!~s aJl'illlbehawors l(oUidle:.

tan

~,(';l

I';lxp~l~ilml(l!liIt:aUy

ml!lliiliIPr'liIl!l!ted~by!:!sk~ll'!g

aJ 5ubillil!ct

te

{ho@s~ i~t betw~I';l!i!! A afidB. aJrtd the,~ by as,kiiii gl tliI'E: .$!Jbj,e!!:t to !:'I'1i1!It'e aJSE!!XI!f!di ch(li·(~ ~twe<ef! I( ,1'!liildth~ Y!l!iilho5!':!I~itt!~ ~!'(!,~im~ i!t~s!t rOil!lli!ldr=-.to yij~ldl a !]1~lQ!tl';llrrh~n 50"'/0 pr~'£!r~I1J(~ 'rlL'lf ( O"!!'erA t or B. Tille ex,!anaJti.IlJilo~this Olft!:iDllIU! is 'that the 1~1iIc:;1IIQi.S.eri!.ii~1i1i! has: 'h:),d lII'g~,u·eby'l,1b1N!H~ o:J 1~'I!C!t ha.l/ill'll) b~~1i! s~ll1,ll:tE!<d., ,!:Ind 't~I,IS sUlrier~'i iii (Qin'illpariSlon to C. ~:g,an fit ,G~: h!Il.W adopted !Jhis: ~ara,d.iglil1l, UiS~triI!!i' .m ekers f,~ !il!lri IiIgI li'ilI110w.alrili.lruJbiUld .. il, Sl,p ed:mlm ,ail' coaolied MB.M:~"to
illl~!itigill,le .;the; eixni~tllllII(lI'l and resoi~liI;llio.1IIo~ COglilUJiVEl di~ol1liilllil~ein 41'"l{€ll3ir-oW ,childre'l1l anal ca ~uc;hJiIl1i 11IIiI1l'lIIkeys.IJIhe'y fillld ~naJt booUnsil!lbjie,(t lfiIioods be:hiilv'e sijimilady; tlll.<lt i:s, ~~ml C ISinide:ed~b~Hien sigilllHkalniUy rIiIOlre ,QUhe time: (60g./o)wi'le'l1l ~ubje[1:s hCIJ'l,Elbeen Illlil1km imlto i3J stiltte of Hig n]me ,aii5!>oI1<IInIU! vila iii fbt-mu nd ,!Cliloiil:jll!,f.A 1{€'rll'lll~; B"illlld ( is liIot5lElLedeid " IlirUl!~'l~! ufl:elillwtnen the'lllJ bjem dire :5:hli]lp~y Iil'r,e~elnted in,lle tfiiirst !rI)U lilt! wiith A. olr Ba5;~h,e e~p,erllin enter's, thoi~!e.-G] C ~YClmL 56. lEI, '97·fI,r20nn

~ 'uuing a Pox on Cancer

IA.dvante5illl geiile dllerap)! and o~t.eri.e(hI1lOIo~ gJies I~ave lilIe~pedlmevi¥e~he idelCll'~llatviml[ls:e:s calii) be l~il'rn:~~edwdes.trJ(lytuIllllQlr cells, IJver ,I dio.zen dii~t'iml[t¥a IIIlU'ies of virll5ei> are beln'g en 9i~ m~erredltoopl.'i!1l1~lethenr ~ol'lcolyn:nct!' potential\d ~.Ie.,l~eir i!llbiliily to repliial'tein ,alnd km~l!Imor ; (elnsiUi:l.ihollt hiilr 1IIl~g m!·omliillltiSis~e'. AIm [lng n ~ tile!SI!i) wu:ini!a, vbm,. WhOSie1 deskable me:a'IDlI[@s as an olflmlyliic agent ~Indn.u:reIh,e i1Ibil~ityt(ll ~ ~ .$p:r~a:d rapJd'~lfthmuglhthe: b~o(liJ :1.0 epndtumaL ~tq~~aj'(5 a ibdl ;31 wLl'1l9Li'iltalJlilsh ~tl - pmme!'ilii s.a!fety ~ ~ i'ltillil,an:s beciiluse ,Giils U!ie as (l,va;!:one mtlr ~ $liVlaJ~lpoi!li;, ~ lwo ~:ml $h,!idi~slll~g'hinght ifrI·e: i~e:J'S~I!'I'''Ys d

i!it1Jpafila~lly,.lhe~,apeytk laJa~~it.y 'liNtS, :seePiiiIIj:hen t~€ \I1lff"'S~S were a:dm~imi5U:r'oo ~5t.em~C;gUv, ~hli: d e~i~erv iIIi'i,etl'i(;d m ij&t reLe'II~f1ll f~H cUnf,ca~ thera-

thil!' i'lllth(fr'~CiOUli(J gi~n,B'rili~~sta'blll p~tt~l1fl~ ,a~

sl!lF~lO nm r~so~utJlon, thotl!t ~11~f!~ed(l()r M I e'tdli n!;i er il:<id ation ~IJe;p:s,. In e mailll a.dva!fqtage T

p,ie~ ti1l.rg'et~!IIIg5'(1lijdn!l1:Ii!ows, ~ MI't. orr this metihod,!hQygh, !kI,I,gs~he(;i1!IP\adt.~~a 'C~" 1, (Ii)!!,m~~i, :U1,Hln",l2~ (U~7.2.7(200i7~; ate Sf!'N~r;:li~h(!O!1rgrf!il,alcQ~~!i!gs g", tl:rin 9 ~ass Can{-el R~, ,61,100(313 (:200'1~. f~bers, When IPi;imped ~i'i~ a bhl!::~~se'~ S~~I~ ~u~ltravi1ole!thump, the C10ated fibef'~ ei!flllW;ed .;I, reciJo,rangle glow. Adding er~jllilfl dil~m'l1de1.0the IHSQs,todkso!u:nl(lln IrJi!lve rise 'Ni a 5OCCH:ldphom.A COilll~: of ,5Ukon lu IIIllnl'l'e!'S(!er!t b:aIIlIdli:lt wa!\lie:liE!nlgt~!! re'~e'l>i31!1!t mou a,~Uci:ll [ornmulnk.al~ Ollll!>. - MS;:~ SiLkolii IFIIltlll>e!riall5 'with n,morneB-~cdle' mnrplho~.ogi es iIlave ,al wide I[IInge o~ I~assibllephoAd~ Ma.le[ 1[9, UlllOO'2Iadm!il"2!OO700H1 WID?). ~onk i3lp,p~katiiom,~iP03inll1!in:gIi'i'd1iliHg lIIide 1Ilf1llpliliers, Iligllt'~~liIlIiUin'9 CIi.IMAU SCIIIENC:E d·i9d!!!l,. ,alnd la~~r

ea ia, &:~,M.illrlg IiIl ethad 5 Ier 'IiJiIOli I\;,ill1g

IiIl

W,el and Dry IDati ng,

~flF!wMchv,a(dn]~ virUts is; being redes,l:![Jnedr(!f 8:. llSN$; ,i31CiiI!l ~rli1 !!::~,apy, c TihOM~ ft' at, gene:rate:d
00

::1!

stra~i11ofv,acci!l~,a Ul'aJt O~ s<pedrk,al~y tQrgets

t::,eII[~ with ,ac:ti~,a!!i(Jl'!l~f

'~mb~dd'ed 1i11 ~m~ iii

Ul~ di

s·]~iwfl

1i1i111i10ICry5,~!il,I$

A fUiPUdI(jmetll~(jl ch:Clllil!~gle ~n (!~plyi!lll I~( dlati ngtg, lJ'a~mcea!1l(Jg,raphy ]$;

lh at the rad'iCJc(i~llo!1 age: (If

S~l1! :Slllr~

~miiflo~

tIr ,anlscrip'UO!1raa(l~

o);)]de lI1I13illFiIX (I!lC-:SllSiO~) gl@fter?

~ 1[.2fa,~d~~eepiderl~1I~9~~hf~al)lrr .re(~!)ID~ ~ S~gffii ~hn9 paU1.w.a.y, a!ild M pflodl!!()~5 ~If!he t

,aJUy li!indve'lIlude"
,at~Qi!iI:fu:olllil ,g, sHioofi

...
2

~ tUlmOU

\!idliii~y a host·,enc:oded ql'lnlC.il"!.~ (GM-CSH

'oxide

~
~. ~

E
15. ~

S ~

tha!Lalp\pear'Sh':I' ,enlnam::e the! ~odyl~aJfIIlitumo:r ~'n1iI!i1I~n~ reslpOln~~. IMi ~~depe!lidl~f1:t Olrk., futa W Z ngl t;'tal. ~'rI!~rted ~1rI~OUile va~ci~ia g:~nom~ ~raml~-' glen~ elillcodililQj tnnN!' d~~~erBnt l.ij.gh:l.-emllling pr'Gteins, a strilb!~ll thiil~ ilIUGwed ~Iile antitumo,rr activiily' {IIfthe V~IrI:I~ be 1IIl(l1il~'Ioredilli rMII. UIII1II1' to, by op't.i:G:lJ~mi!l'!jil1g.S·ailh vilrrl!ls !ltraillil sinauced re,gre~sjkm 'Gf ~lIl11lmSilli pr@(JiliinttiR models a mid"
-

~6istalildletchiliig b~c~ni~i.le ..H,~~>cl oi sh~1IiI et' 'l~ill ~ c-5:ilSi 02 iCa.m] ~1iI~t'eadbe l~re~gJre,d$: ~ a
t~in-n~m, ~mater:1:al ~r,ouigh tlme delPosJiM(1n '(ilf :5(1Mi:(m~.,(jIf hydirogelll s.1liSie$ql.l]o>!alrle n!SQ~ r1ollowed by' ~herrn[l1 pm{e~5']lilig alllOOI!lC. I~~ (m~~llilii kin 9lllille' 1"115Q ilI'!Iing aln elh!lI:tmn beiillliJ1l,

~eq,~fire.~~bse,qu.enl p'a!l'l~rl'i]lf'lg 11lI.~ii"lga

mm ;gUIld: .if!'lay

f·aJC€ w.a:1e~'i diiHeFen t. 'fflroml l~ at olr~I:i'e s ,~tmo'Sphere' aibove 'ii, becaiys.:e !!)If va'Y" in!) ~( producttol'1l a:f!d dniS~JriIb~tJl!(I!II p'!lthways. IIOiJ OW]liigl '~hisdif~e;reJil te Uerm,oo the' m'a,rifle ~aL'ilil:lc:ari'lalliQ ~eserrvoiirag,~) 'im! ~p~dfk lo La 'ti oln s i~ ,es!Oenlial for e~tdibU5h il'lQ i;ompa ~.i;lt,',lJe clillrolrlomgiil1? ohlhi:liflQW5 iilll oceal'l circll!daliolrl <lInd eli male beM€,endllU,erelrd re,gion1l5,,!i\I~tlh the fUirliih,N ai mow exp,lolli Iillglln e cau:s,d mEl(han~'~m'~. S<lrntJh.ei net {Ji. Im<lve de1:elnrrnined r~elf"'l'o~r ages, lor 'fOil r hcnm~l( all1d Jiitlci mt,l!r ~O(ilIt~lDn!> CMt:inU~r1 !illPrJfllt 7J'5I.

7117

betwe,en 23~OOO !lina 111,O()Q years befo~i~ ~he pm:BfIt u'5,llilg ,~Irad~oG~lrbj)nplt!IBa.!ru·tullilill(!J t.emlm~q!lle. nelre,nds 1li'hi3i~.tJm·ey see rl~!ruire m,a~m eJililIlIiIge5il1 ,deep om!llfl drr'rntI ~iiltiOIl d ming dl~He!reaMiillit@rvii'iIis air tine' U!!(orlll, Two rn iijor lItiIililO,5l!lhll'll( U( p~,iMetlIU~, ring the en dl .of Hal! dill Helrmn til: 1 ewntalfldthe< ~i31r~lfB~[~inglinmr)ltI~ d~I1iI,.()()~i!irC::oi1l~ p;or,ili'i'OOilisLywitliilhe ~w.(I"smp

~,10nlele-ctriC.:lUy and mnti muolJlsly by llaryi IiIg l~e amo!rullilOrin~roed "ip;j['J from ea:dhinj@C!:olf. 'n~s ele,tllf1:(;i3L (oll1trol ,ojf :5:pil'll<I(!(!lImllJlatioJll presen15 gaeiilt simpLiiric,atiolm for fu r~lh~r d ElVelQ~IImm~ of
';p]m!~rolld(;:;; circ;!lii~ry; -

i:I

ISO
1, l

:Phys:. Rf'v•. Lett 99 16M'iOl(2007D.

earliY dI~'lada~ !ll~ 'in altrnCl::plh~ffi!: ICOi IXlHia~. p~s!!!r~~JIld I!ppw,r 'to rreflectb~ U~11Iski rof ICO'2 hll!1l! ~!~~ d~H~P\!,.~antoth~ aitIl!'lO$ph~re. Th~Sle: resllb imllb'lihaJ~.·]~C age ICgUil~r,aU~n~s(a~e:s Mil

.Pig ~(ILdi pl~nt; br~edI]!ii!gl !if!e'thods ilI,iiadif!lQr~ !

m~edto be C)orred,~d ,a(~ordiiml gt~'. . HIJI5 ~

6~p}ly.ll. M~gf"

reclet1lt ge~e nalii!sfoITll1lthn'l tedll!'1Q!I,(lgfle~ hall€' ~liItrod~(!ed :iiiiiIIdfi~;edgeliile'5'in:order 00 cl(InFer

gd ~l'It[!QlOOI!I!S trailS
0Iiii1 cro~s,

S~r; 1173"US (2007).

W~eliilaU"ilt

depe~ ds (If! (l11~ 'ge'mie, the prs(j~S ~15.

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spfuo!lI_,

IEIOIHD BY (ONSTA~CE

IHHDE,IN

Way Up North
U MIlS; big of ru·ctic ~ea k;e rr~t:lii1edtil r~oord I~G!i\I !il.lmm!IF (Sde-nCf, Uil~!l '5 Ol1oiJer, p, 3:3). AHhe Arttic R@port Ca:rd ,2007 Web ~i,t~,p(i~~ wattlllff!i Calf!rac~ t c,~ eW'~il';firc!ilil1ii ~mlUd~11~,ng~s
lImeuflt IflewS,whell

U'le

from 'tfie U.S. INliitic'lilal OC~iiUil~C: eric Ad'!iliirIFlisua'tion, !,Ilpda'te:s~aJM lI'eaJr'::;.SWle- ()f l'h~ Ilrf"4'" ,"'"--"1ft 1",. - n"'l~ii b:r~~~'·~""'"t--""II"'".,,€1;ii 1ft _.I;t!, " 1'1... ,n ,..p... 1,1'1' O__ IP€"" .... 1.. - >ii i:!1~[1d~es(In val11}lb!es; Sil!u::1iies air'teif!'1[peralyre iii iiiidl the iI1l,a;ss Gre~Jillglnd'sk,e Sh,eet. ~o!'le ler!il!l1J of r'e!Je8!1:s~ ,iii "h(!lt. spJ)t"wJ:!ere tem,peratur'e.\i am~ 3" to 4«>( ,above ,~rW!~gg~h~ edgedl d~serrtg IEmo~ehJ)m its t~rev,iClI!JS~m"liti:m"lin ~351lE!fnI
Ii! IiildlAWcsjlh
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~ntheffar IlwID, ne new s~t~.

Sii~err'iiffi. O!;l'eri1l~l, Afftie cOl'llinllLle:sl:a Itrieat.lI~, bl!llth:~ sill~ notes th,a;I.not a~l me-asme~r)(lilow the ~nelncl. IFor ]lilist[lrrl'Ge,pe:rnlil1larros~. tempe~[ljtllrl~ i)[ppe<llr lQ Ibe l~eve~inQ (lin. » WIlM,a nr:l:ic.noillllg ovilN'llJ'Drtcard

~ne

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#!ltniJOlst 3 yeQil"S afte,~ alsu!'iil!mi lJatIJeJ""'€,d coosts thool!9iluJi!!t :SQutl'! .Asi'iil, Im:iia iIIaSiu~~ed a

high~'t~ci:! f'a~'lY\li'a1f1iili!lJg (emit,er that iOOllisSll!!e allmsflor'he kil~~e~wav~s:witfuii'l13: Wi~n1U:leSlte~ a "IVi eaJf~Ih~YQlke..
'!iih,ef1IJa,tijOf!!:!l ~~~~~.mj!ilg SYi~ejlil fur Surges; in the flildf<i:U·1 (!~ iii, O ~ h,eoa:r:iqmll'il.erOO iln Hydlerillbad, will1:.ake "abo~t ~ 7.1m in 1lIk':~to alii al1{le the realn1hql!l~ke diata and! ~ illlitOmelr 6 minlllJte.s:to nun !>imil!JlalkHInedels.te r ~ ge<nera~e! ale'II15," S<I~ Ill'Idia:'", :'lc]enl[e Dlllllli:!<~r, i:!! t{api~ Sib-a I. Scielilitist"l are Mlriijll'lg 1JD IrEdLice tJiI e ~ ~ [llmloun10w tim:E! evl'J1 JiJmtfule,~; lle &30 mlilll1101'1cenler reeenw,s: dataholl'n sn~ g ootoolilil-plm5Wlfe recm:lJers i!ll~ta:l~~d dl~'p,illlllJoth ~ the 18Ia,~or Belilgial ,and ~lheAraiJj<1l,n :5e13l.,II111d!di~ tiollll, 30 tide- QllI.IJ!ges: fuJiii;re1J~1Ii inst1il~led tlO~lrad!; ~ tSlilllam~ MI,I\~, P~~~r Ko~t~Fllilllililliln\.UNESOO'.s ~ t)unam~ oo~rdiilililitow, 511y::. India's f.y~'t~mi) ~hart ~"tQm,plilte:ly' dir'r~rl!IDIt" from IhElIP.a~if~i!;1iSlUilili iIII~: 1
:5 'j"~I!ma,liI"1ii a,lil~ Storml

Ka,JlI:Z], a ~on(looat tliie Gf@:at.~ Trust of ~owa.'9ftfJ@rs 11Ig~n1lPS@' into ~is liliI'iM wimlfl:@,t~:~, !liItJlIl~ '~l'I!Ii3Ik~r11t an C!il!lliiiJ:it 'rni ap~ ~fI~~thlg.~ (lJmn~y aitZfln~baf~ (on~ MV1!nhn:@iI1ID~~Mo~I'Ir~. lOr 116 painllillilgs, 13J wer~rsflaIUIii'Hj UP][;1 iIlil'~ Ilrst 2: days. Jilis a!~!jtrillot.l~iece, wilill ~he ~fiUJr~!!,(:i~coes'" K-.ilJllQ IP~,~ets., b~(ll:!gM, fill USOO •. l~rc(I!OO~ go 110ape~cm~nr.atJlQn illil~'~ wild', KarlLii!:; cJlIiIl:y a 1ll'I~liImrma:s~€r ~Gmplilr~d with till@ Idte mim!i' CO~giD., ~hrll:@c:f whos@ p,aijl'ltilllg~ {Iiltcli!ooa ~e:c.aiid $,,25,0,00 ,ait. a 2005aJucl;li(!lj1r lnoollildolll.

wairr~i!1Jg and .Mitig~I:f:(!111 )ysh;m.s:j~"!I!,.d~:;i!~I!J;;:!OOs'lY l1!!ori!Wifiing fII11!l!LU,~k: hazilirdS ~u(h ,QiS 'stll)fm

surge's,ty-phoo!TIIs, and rises: in sea le~1s.a,nd

ea:l'ifliIqu1lJkes.

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p~I~Mtia!l ~10 00: '!J1.• 5, Ilres,i~e!1ttl9l 'CiilJl!did ales" 10 :r~UiIdllP,eop1e~~ 0 wouldlil~t re~~lili:i!eev-e!il Ctt!i!ta:li1,his; team elliliiSt:ed 's-t~dle!'1t~in South Ausla:a!lla (liild 11'11Ne~tlllgroili!., New Ze1lJland. Cli.liltCl:n''!l faCE Ii\',on Ime C!omp,el'Mce race--

S.eliJtI~DrIHmaln'lt rClillmlFi (D-NlY) ils headed fm lh~

Whir1!E!House. :5oSiliy p~edic;tiam; based oliJ"faciiall (o:li'rnpe;telilce" a~ a~51~sM by----tillfl cmgl o~lhBfSIf:I,!ewZ&1Ilil ~dl ~dmo(llfllirlli. In! 200S, p11-Ycill(JIlbgi"il Al~ mldier Todliiltilll of l[jlyjnc:etlm Un~ers~ty

&!

,avewaglmlg 7.2 on ill .rI(ah~Cl~1 m jJ[{}-4it:ik}]j'jIecl hy (,e'lIIerri3ilWe5ley (!lUi(: ~m:l Senator Bari3id: Obi!HiIl11!. (I[HILl. lI~eto.~ th~ee Re'pul[Jlka.mlS'.Semil'lor j.ohiFi IMc(ail:! ofArizcnna, lllepmEC'Sem1talhre D!Jmca n Hl!ln11!l!ror CaIWfmnl'i3i, anid S malto~ Ch~d: IHa'!le~ or Neibra~,artrniled six '[i1emOntlil.'S, tying at 6.:2. !hie lea~~· (ollilpetel'lI:-iaiJiPearingl
III1fre G,O'!l~flrHilf

; I"'!!I! z I.
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:;

report~d f!flSdellCf' tlO

June 2100'S, p, 1162'3}llhalt p~U~dli! [itS WhoiS@ il!.!!dged rn()SI: '00fIIiI1l11:1eJ:lt" lCil(JI~llr!g ~y p~CpLeiWftQl

Slilt

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1!iI!!!ckabeil: (Jejt) aim:! R,'ieillila!i'd!S1)!l! b<m~lnd inll,l!! "'1liu:iai, ()~ml~!!UIiI(]e'" race"

IRkhaJros'Oll ([lb.INM)
!i[i1i1Criorlllil~r gO~i1irlf!o\r Olr }!i,rkiJIn5as iR€PI!!iJ;tic.;J1lJ

~ ~ ~ <I;
Iicr.

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o -- ---. ~ Sl(~f.lr~n ~howS~iredi(1l(!d dii:!'~(t,iMil!i!.of iii mlllt!)!' ~tSl!llilaJlm'i~ ~5, mllnllilt'@Si!llft~r a maglilltu1dl@"S.>!\1 !!i r!!;;iillfIlliquak@ ofHlile '(~ilst of SUlmatra 0111. ~ .l,Z S@:Ptil!r1i'lJIelr.

~kl'!i!'l recogrnlize ~hem~end klwi,!iiI sle!l!atonal electiQns.

T(id(]!mO'lJ'~ported oliil~liiie' 24 Octdbel"ii"illh~ P#)t:,wfil!l"gs oj M'I!: N(Jlit;)fliJ! Ac(,\deml oj'Sdetl'C€s tl;I~tlhe' ~hn)ique ~ad a~IO(]l1J'~,cU.v fo~ec:a5,t fIilOJle tlhal1l~D·tMfds of 89' Irace5~Dr gOV"fmm. Inspired, lI'IiIal~iketing pro:le~of]. $!:o'tt .AI'm"llr'0i1ili91 'title U!llh!'e:~s,i~y'o~ H>ensylv[l!niill '5, of Willanon Sdhool. triied Hile test with 24 reslasd

,a,1,!'!.'9, the au~hors rell(J!~t if! ,ail'! a~'1!'(~t"~nrpW!b~ished paIP~r. IH"'1H.iil]- lpioop~e- 1,.",,1\1;; 1,-ll.. JI"=!;J-I .. ,.. ''"'' Tod''''roV' ... ,~~,~ "1'1" tl"d~m"--.',l __ ~'''' __ . ._'" ._y _ -~-, :Sg.y~M~ ~~b"$ al.iiiiij)lllter ilItodel 'indiicate; 'IhQlt ~mo:1'e (!lmlpeten~ 'fa~:5< ~~ IiI'1Qr-e m!!lt$culii!il~,
Mik'~Hrilr.:~bfe,

wi~h :Si~IJi!rei~lH5: ~!iildhig~ che-e~b!1lnes/W~el~S:

inqJl!illIpeten'lra(."e$i3.re mOil:e rCll.mdand babyish, ThIili!:':Sfor lin en,illJl}lWilly. LGm PUlelr5 .have ye:l:lD ,aer-ine ~he l1Iill..uy m!i'IIg~c.

723

EIO~'I"EO BVVUDHIUT

IBHi!!rrAC:HA~JIEE

Pioneers
GUJiB;AW. AUiIOIIENCI&. Urlii'llersHy of Catii[,omlli;! (ILK). B!\l,rkJilleoy. plmry:slCi;st iRjc~ardA.. Mu:~I~r ji5 '9 ~tl:irlgl ,a mste ,of YOI!JTu~,eJamie f,'Or hj~,'effQmtolleaclin oon:sdeme' rn,ajors;. last Ill!,onthl, ill( ~e'f~el.ey' Ibecarme the ·fir.51:~.rnver:si~y to po:s~ 'emir!!; coursesen 1he Video-sihan!lg Wi&! site, grntdlMu~lel!i"s, "~ysks fOJ ~~IW~~ FI~'e~ide'mts"~~~ br;el!lllhe' ~'u)~ 1~()p~I~I~ QHeirri!mg.,.~151mJltrodl!,l(.t):l¥ iedl,lte, "AWI1!lOS~J'll[:l Heet," hai5 been Vi~ell'l,led9Q, 000 ti!11!:e5. Ml,IIll~eris: dle'iig!~.liedthiit I~i> 26 .!~ectUlre COUlrr5e,w1hW'lI~~I~'eelli grv.aikilblre on tlliH!$.'(ho ors:'lNeb :5Jt!e feu a fm :ye.!irs. b'S!lIOW Ireachilllgi din ev-en i:Jroadelr tludie;rll:e. He r'E."t1lU~Ollie e'lr(Hai~fmm,a mgh :5dlO!lJii~r l'i!!1l MinnesoltaJ 1l'\IOO the l~h'jl'.5-k5:h'e iej3lmed ]lrQm M!,I'~,~err's.l~octlJrre>egrll£\d [him S~t~ 115lPo,t as m~Gtlp~~rl oftile ~klllil(lwitedge mlaste'[) 'qUliL 1!B3m"1I1illd' ilmp:Wllf,d ~lis;1I~,ti~·de tm'lltilrtl sdteel. "vUhar( i1I:s.weet thnllllg for aiB1l,cller tQ ,lheaITlI~ .Mu~rer Stl,1,{S" [)espl~~ 'hils ,glo~\tll weilch!, M!i!lll~M ~asnl't fOfgronen his hCillilileaudi,ence.,. To !kl!,ep ~hem cal'lJl]ri.$j1 to dass, he!uses ,m III o[d ·ra~h]on,ed triclh~'~'p '~t1ll::e.!I~. M~nlllilesQI.a(S'(ien(:f~';,J.4 .5epterlllber, lIP'. 1417'9)-' !i!lfld f,eelinglhgill't€! hadl d0l!1e~,aPH~~tY9'OOO IHOMEAGAI N. titter just ,2. years, alll[)l,I~' j.Qb" iii! lluk!e--hiea!:lillli!)llbad: to, EMtrTmorero UPlI~vel'5lty' ~~dIa SI,I.!ifII1!IIIl!r ;p;e'nt wsting the s ofl:g ht dt global scourge ,m ke> AgJTe! "w~rmlatl po~i1jQ~water5, dlellifi'isl'Y Nob~L l~al,llrea1teIPlete r Ag,~ ~s re'lllirnhi'~ll1Q ]ohl'l~~opk:inlS: Uni~'r.~~Ly 1[1 over," he ,,>ay."'. B~tUmo~e, ,M~l~nd.r 'Ilihere Ime~!pel1l ~ ql,iialE1i~r~ Wl~~ ~ ]!HMRI glrtlll'lt ~rre ho1lditlilready' ,~mLJ ny ss 1:1 'r,esoof'(he,r. Ag r'e wm. becolllJie ~~ e begun ;ald~p:hg hlis: pliiz,ewiinlnJlrlIg re:Sie-~~di on ne,w d];rre('[lOrof the ]I(l!~rs If.!o;pki milS Mabnlll .1i,q utlpil!rinls-IPr;oteirlS that form IP ore:sirll ceU IITliem'~fllll'le5,.,-;lQ,r'O(]L.lS (I11fl1 thllll.1ilrllng the Research ~nl)lihJ1~e: (JIHMRIi}"rl)iljllilded 6 ye,illl'5 ,tlQIClWl'ru~ a :SlO:() milHol'1l i3lntOiIillYIOOUo; doaatien, malaria pi1l~tlsite. He :Sti"y.) he pla MOO IJJ se I~~s lihe lln:stiilllJtll!has bsen Ired UI'I'l:i:l. oow by star pow@rto r\l1O'urotYOlingta'~@'llll to 'me SI.'udiy vil'!Ologist lDi~rI@'GriUijIl. who i'~S{J chairs the af fl!!lgilect~dI d isealSi@s~ m ~OCllLar mkl'obi:Qology ,and ~mmun.o~()gIY ~ depal~t.mel:lt. or wtiidl it is part GlifiHln sa,ys,she IFROM ,AlIIRlO !ilEA. Sm:an 1\'W.ery has, beoolne ~Ih,eril~:sm woman !presld enla~d dirlocto,r .of m>e ~ ~\\ld b~€iJi1 Lookln:gl to' r~c~uit. ,al nlNl! le:aoor for Wood s Iio!le (kEl~nograji)hik ~tl:~,t.tluth:u~WHOO ( ~ yeall'S and hadfiwst oU,e'J'ed ~e jiab to' A.gre lfili Ma$sa(hu~Us. ~~~O<lIIly' ilirrt~ l~e ~~r'('ed to oocolfie 'Viic.e: '"' ,d~'ii.m(elbn rorr scier;!,ce illnd~och'il'Qwgy ,at, OIUke"S' Allery, ani 'lltmo:spherk pl:!y:ski$l, comesto z t~~e n-ye:ar-~[d fLQl!i1Iprofiit f~of!ll,the UWliiver5ity ~ Medlka~, C'ente'~in .2.00,5 .Afrer givli!l:gIIUl P 'Of! his; of Co!~o'!1!d'o, 18'OuIld er, w~el'"€!, s:he was ttl'll!: flrst drearn~1) nm iil50a 20016 Seriate (~I!!1ldlidah~'fox

(Mperat,ive Instiltu'l:e
r'Or

"m m3mIito

~eald the 111'11

ReSel!lHh

EnivirOfilifi'ilelltal

Sciences". She '-'h'ad ,11 strofrllg ci1lpabf~.:ilyr'or wisi ng a bOlJ,lle di~d:p,U[l.!lry d is(lJ sSions iI:i,n.dl ~H!IHi Ilg olul nll(lrrlj'Sd~ ~ fIilry I~jnlkl;"'" says a ~i

I' e
...
iiiI

Avery shoulld m~nweU[ wHh tlbe '0(:001111 seerees because bo<~~dllSdp~ilmies::lIre f;eld-lb~5ed !1ilnld IrelY hl:'<a\l'il.yoln Im~dell'!ill.g, Avery,. 5,7,~y.s she plans ~.Qmalke the'iflst.iMi'Ofll!inQ:~ei!'lterdis:dl"!lifl~'DY glnJdmQl!le~!1vd~veidiM~1h providii:l.gl ~1'I!1}w!~edg'e aloout climate oh.;lnge O1lliildothe,[ sode't~li5<'5ue.). S,he 5:fglrts:ea [[y Inl ext yle~lr,

ecologist Calrol. Wes Smill1 r "a pE\l'son with vl:s~orl1i." WH 0 rs ,acting dh·e'r.:trir.]am€~ tllyt12It. pred kts
'00 Illll3Q1U@,

(()lo,~ aido

wih,o, al~~'O ca[~~~er

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i
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s il<
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!l!i

rlie '/>kq;!1 Atl'UJ,~,fs.edl,tedi b:r Adam .Keiper, has i1pp~lediillSoolIlserva.bve p~.lo50~Jhytolte~I;ru: cm'mg,e ofSCie~'CilliI.d tc\:;molQgy :i!S5ue:~. 1IlltrlID:1ibth. die L leftc':I!ea:nilng ~~l.il:l!kt<lrntk Ccnte~ fbr f\fl,leriCaifI PIlQ,gres5 laurnlched Sd~l,ict' PWgI"ess, c::ditecl by biio~1roci~.kml'l:dHII:I Mor(;;i;!lo.K~i~:I ~Ieft) ~!ll1kiothat M!()!)~IlIJ)~ journal: "has a Jot to sortout" ~,n&:rillliing noora]pooltrOl1!.'l Oliill scienoe i.ssli.feSn\...hereas Moreno (ri!gh!O st!gg.c~tslha)t Keiper's §1!mPn!1!rn ~ffcJi":S"~vcry dark vlslen" dmt m!on~K;itS.S '~roo.kl:ls ;)!ni!'!m!port.ru:n: pr.!i~t ,abwt tiltJ !:'!~d to
ne4-),"OOr-oldjioUirtl3l 'WOWYfID~utUl~ cllIm as\Vdl~ ~
~(;i,e!i!,C!~1lI~'li(,?'
:lI

S:fSlle'. i!!oojhearriva.l of the Orion l[n·lI!l'iISI~OI·l:.<IJtJioIJ~] sysle,11ll1,. 'flitose~ will be 5y.e~IHwlilrellethe Unl~:ed States: '\\'1'00 't'b!3 aMe,1:o ,~~tpeo;Ple iilm.tospace .... ,. As 3. lriiitl:er of
mmtID:IiIiI,1 pre.st~I;'.this

~"~m~l sciefloo.,"

~ ~
!:l!l

Q:W~lt'·~ tlJit~~'" 'Ihe tfJll~5'! mo.v,~b1thll!! :BIUIsh Adimiillilirstlr.aitii,QIlJI

OQ

be il.vciclied", 'ntis h. of' crnn;se liIIot :shnplly a Bush A:dnli~lis,m.,tiQll prnbl:ern.it's bil!lld~tm:y presi&~. ~'t~ ,CongnlSS, MOFief!,O;:Wnetl:!~f~e~"ve i!::al!end.lI!ld to, or not, they'\r,~cwea:red:ill terl rilibl~ merale probhlM ~n s¢k~n{;IC~ ,~I:11!et~f~~pectfOrr '()vid~.nce. •... . .. [TMiI~y] Sit;a~ fOf :sO'URoeS ofp Iuri p ote.1W1 stem ,c~118 though 3;f1 tlhc,v doJ'!i~t n~d ttl< :a~SQ eootin ue wor~w~th cmbl!)loJ'Ih:: S~elfgl'C~US, Tbis fu~wUd:ly ul1i~mr~1IL;:d!by ~:he 8cieM~;.
rQ~ WhY' pu~ti~h ~o!l!lm~lI;:
~llr;y ...".". a'pl!!ll';~:l' .I" ..,

gn, mw;ht

10'

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~ u
Q

K!eipe,r~ 011 ~'tt:ln oo~rn~~~~C: ~~hAdl11imtll1"~ti~ i.ll 2001 d~]~~H~d B poHey Hla~:'~in fflct as(:ns:ib~e ICQ"llri~lllise:,. ,!:hat does !:lot v:t~~! 1ThascC'!1t ~umgln ]i:feas: 11!:csQul"!;.)e tbr -ex~~.i.tne:l1Ihtti('ln,

lijke:y:ours:whe"WaI!!hi!i'!9t~n is fl~@ldool 'with

Moreno: That's

<31

~awd. 'Olle.

1~,ir:J~i': '!fIle ooru;.~fisst!C$ ""''e ~1I1 \wifu , , • !ID~. m)~.9TI~}" uictly flC,letlOf,l: ~ ~em~c!'!!sj ~~l~:t'~ cthic;~1 !1~MlIp~ilo1i~hiil;:a1p~fi!to:ns, andlhey sh(lJUld q

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bL;l\vci.ghe!d by po~i,c;ym*e:!7Sr ..
MQHi~:o~ Wllilt the~'s ]lJ;ot~ tj~e vision i1hlg. Qur rob:: is to ~:ooik UlOf!e' boooolly art~[~!e roh~ oFS'CielX!:e ]wAu:lerica.1ll ~:ifC.

IQ: lind tli1t;eWG.rst ~O'!t,!!,? KJe,'ffipen:I'm IJIITi.hflPlllY with lim gfl~ :betv.re.en the ,e~,d of d:le sllin:IruU~.e

725

,AlIIliil,ttlef

o<f WD~:li. Sellai!l1r Il,a mbalra l1loxerr {f.l.-iLAJ ~~ tI (:tr}C Oh~(tgv j I\! 1:1~ (i~ ~h~di n·9 (.liJghd (@",hi:if beifolll iii l'ieafiiw,; ellfl IhGillttl im P1I~ or dimab! dll'J IIIgl;!. bet;l;"reen t~,lel'CiC' d.:r1iRte~tW.1Qny;" ~ol'tsfilm,d~.ngs andthe

C UMATIE CHANGE

cOle Director's Mes,s8gle' on Rislk

I

B~e!" called dlC 'edit~lg 'dle; lattl~ example o:hhc Whilc H.,.1:,ni:1i(: ~·!nl:(::rIlblft1lii!g [If'lliHl ] the sc:i(IIltific facts,"t\nd ill prh,a~,. CDC scientists 'lili.tef'eOl.!Ih,g,cd .' 'TIley gutted it," saId!omC,·tFor nhem ~., !iiaythal O~lCl" a,ge:mu;:ics had ::!: poo~b1.e'm wu~ it :~ jlllSt ,8 ,\Veale cover."" fhlll' :SU:!l"l'l;li>~~,g the seienee," Gcrbcrd:ill:!;l: t;~:y$ she ,g{):t :;IcmSi> lser message, lrn8lme:l.y. flUitt' i"fm11li~. ~ publle health pe:r'sll'ecti.,~' tjlm.at cI.i.male ch<m!ge is an impo:riani:,. ,i:ssue:' .Bnt she teld &i,~J·lrntiml sM.e l"e.b'l:et$ itl'iJJaJimeiJItCicleJlit hOI,S·''n.'a.lsed q,1I.I:e5tkm:s About the coodibil:ut;y of~le CDCsci.e'l!lCc," Central to the cerrtroversy iswlsether

Runs Afoul lofW,hite Hcuse Bdits

us.
qjlIellC}'

Oe:l1b~lrdnl1igboo1ulcrn.atelyrepresented what's
blOJI;\11il,,<Ibclllt t.be effects of clinwte ,e:h;[Jlge on globlirn IrnJealth, On ~ileIJ,t'!.vaves:•. lPO(' tJll:isl year ru>sigoodl'':IiJm:ed:n.Im Qonfi,oonce" to the asser-

L!.ltc '011 MO:liiId!lIY eve,1I1Ii,lIIS. 22 Oct%er, the jjirC!!:lm oflliu:e Centerslfo:r Disease, CO:UiIi~ trol Ii:nd ~evelilhoJl '~CDC) sefi:led. into !IWjjJ,si:I~

iil1~toli!l hotie~ tOO:1n fo·Ji 1), itua,1 fami Ii ar 'to r blilr,~i;it'fats\Vho n;-gular1y briefla\vmakGffi~ a ~a~e"i1]gbil,erdM sel:l~iOifil,!!iitith a thre,c~tili!l,gcd b. • i'-b· ,, . • fu ~nlil ,ij~g .lb J 'I" r!i 0'...1. 'dj"1;!1g,."ll~!;);~S!:!.j ~ !!i!lll'~it.'U \~ "j,~g~' ~ng tJ:iCl !:I~,t mOO"!d~g befu~ lhc; SCmJ!fI!1:e EIWiI:(llnme;ntand Puliitc Works, !OOfJJ'l!ljm~t'I;cel wlhiicllil was hold~lg dre n~t"ever SC'fJ:~ scss:i(rrl om th,e ~ealthimpaCl~ ofdim~tc ,Q~,a:IlJe. Neld to her w~a .1~I~age.!m:lfl!l1wry o:f t1\te SCiCllltifk fi!!sue:~.pr'cp~I:,ed by ~~ncy mcarc:he:rs, to be distributed I,n lAe he~ing, :B:~.u :shod~.)! before t~le he a.:ring bega.nl Ger1:iel1d:U.l'lg leerned [l1h~1t W~li'l:e Hlo'lllse the
Oli.oe: ClfMI[I~i!lgemenl' and . .BlIdget ~OM:B) had slashed the handout in hal.f.Gone wm-e details OIl hmv d~,mllte;change could wOJ;seJ~,

ies sJiI,O\\.!edhi.!i!her uroonrempenxllIJes, ceuld increase ground -level OZ.(1I1 e. wars ea1Ii Jm~ asthllm and ''cih[0l1i~eI1ll!!1g d~c~~." Why '!!vas li!Cf ,vritt~r! test:i~loiiy;:iJ1~·OO ~ seyeroiy'~' A'Wbi:te House :spokeh\PliirfirJl'I~ii:~d ]:~e ~dit~w~:ro d()!'!c be(1),M5~det~ib; "did~!l group QI~[lrousa!lld;!; f ~dcn1iM8 'v!'iOi$C re~rts Q earned i[ ~his year's. N,obe~.P.e!lccPrize (SCj'@'IJC(:t, I 9 Ot,;rolber. p, J721 The p:re:S.idel~fs sl(;:in;:lloe adv~~er. J![)ll~MaJrblJ!!"gc:r, we~Hh~'~1O .ol'e:oola:iI 2 days~a:lerin a 1i1!1I1C ,exp~aflm:ilOJl :of his I:o.]e. M$'mlJ:I'gel~ saidst3)fffo1)[l1d''iB:pp:ropri.me OOJillIliemm1s betVi~en elimare cliangeBm:ll lIirLTIul!1l he8Jlt~{'~n the .dJid:n Imtclf'htirnzed"several ]iI'wmm:::edbuti.lfI,lport~llt d,if1erelil;C:i!S

of exrreme heat 'liWl.VE:cS'"

,Hill::! tJrni1Lt :sW,.d).

tien t~lIlLIC.~ ~Ill;ate'chi! n;,e- has allleady led 'tJO "mCI\Cil;Si!~,,:I he a t.;\:~ rel~tcd de<'l!th:s:" OMS
~moi'>,cdl \¥otd!il wn'llu~ CDC h1l!im:dm,d describing the "1]k~lihoodofhi.lhelF mortality" ~-t"""'> .~~~ eol,!!~r'.J ~'!""_,o <!,,~<l!o <i!1.."""g ~11. ";1,.'.1 ,,'t"Fm .' h ':It \l.\"""" ,~. (.I-n 'fu; - r .... ,.. c. ".,J;;,. or~1f:(;;[Il"9ir~,, !Gc:liberd.b:!g ~IiII';~IIi![)ljiJ~ddl~ more
thQ:~ 25~«U)~taliljes~D~tkcdt~ ~e

~~i~~J ith~'~h~ w ~,~d~1ons QfUiC .1~.~)\'CrnlJlJi1eliil1:a~[iiWld Climate :Ol~;aJllgc (IPCC}. the (lIfIi

2003hc~t

\~'ave~l'E~.lfropC b~fuc:~ed (Ill h()\ili' US, 0'111- ~ ciajswere deal]~ng VJilh thcpoottk':liu,) In terms O'finfe(lNm'~s; dUsc21~es,. tMie [pee's 2007 rep~triI meruioliiicda reoel1t study showmg

••••.

allerg ic d~se as'es, exacerbate deadly hemt VWIV1e,s_ and bocmden t]u,e ~;e'JD~phjc faJiil1!le; af

Wb:tious diseases, G'elmm:i~!!'; didln'tl];mc:h. As. iiiLwe prese~too her 3~mmDe openi~,lg :iil;atc~ ment, !J, s~[de listed [Is,tlillmll,. ~Ik:r,gi"es,1Jl~,d harmfll~ ai,glll blooms M"flO'~elm,ti,;lru Ilcgati.ve

~ r!jw'tabacteri~o:[Ulbmak inoystcl:s"linireld'~o .. ~~ypicallyhiigh temperatuaee in .AlaJS(1.:ilIll cO<ls~a~ waters," Itnoted thatt extreme: :~,i1lD~ ~ ra insin No rfh AJTIilieri.ml. mld Eurepe ",nay ~: eN!pi<lm" pM!tcrns in cl),pt'Ospori.diollis bru:::IJel;-"~ I,d dli.se3se. ,Both exampleswere oLd;&olIl~,le :3l lialldout andwent UIUl~~eJltioned tiID:, heminlg. ~ at z Ge~;l:u;:,[iIDing~ <IIl'Ib~,~ba,tio1!lJsF'd:ise:<ls>e seien- !!! 'list. ~<I,YS~,l~"roi!eidu 't req,ll[re: her '''to go ill~Cl '" d !b"

l'aeaJthimpac1s:' S:Iil(l~xpaJmde.d ~ooeiss~c~ on

c~ha:i~. Se!lawrBa:rb~ruBo,~e:i

~respo.rl!!\eto qlt!e~~o~~lirom the cOiI'!:1i!'lJiH)ce (Dc..CA), ttlld otlw;:r members. The etU~ didil:'i~t cOil!m~e 'Uip. n~ithe liiIii,flttcr didl1i't em!!b'l;':re. Wjtl:d!lTh l~o~ws•.:l'Cporr!~s:h~dlhe:ir h~dg Qnn~ QVigi~.1 versiOI1. h >aiSBert'cd,. Q.Qllg ·other thm.g~"'dl~U "uUi,!!! Ig'l!!!dgl Ii! S,.;1@!!C@'. S cil~'!lil(~ ii!(i\!'iSIH ]>0 hI) the Unh.ed Statc~"~s cxpcc'tod tiC) see !iliii, 1III_:!l rbl.lrger~'u,g5md oolliirnlrng parts O'fGeir'Derd~ IlJ:i '~, Uffilcrease h~1the se'!;'cri.ty. dl:U"d'li!011. B]1H:I fre~ sclw:clll~ed' Semlltlf ~~$l1lm®illY.

r.l! de'mli~on every singile COOiLP~~(;lltion o:f di~ai.e ':2: dlmge,. ,., .R:ooely.ifever, does the'\cw.uit!;entes~ ~ ~imony !ct read [by the pablic],' IEhll Ri ek ~ [:I'ill:l:, f()ml~rly (J,f'~in!(lWhite HOlJise ClimaiI:C ~. Ch<\linge S:ci~l1Iee Progr~m. dis~grce~. ''Thi~ ~ off~eial ~tij.t~m~~llt (J'lfil, aprQblcli!ll~():Ii!I1 :tlmic: ~ ~ '~p-ra~~il'll··,gPtibl!: ~iilc:1tlth ,official to ~ !';':;Ollgl:4;'l'OS; . ,t rmaJiICI:S, :1il Those fitmiHflf with the prQC~S~ ~~y ~h~ ~. ~ .~ sti ll'OI'll¥. su.brn:itt.oo~oth,e Wh hie House '_. days before ~~1L'l :~.earing. '<"IS velitoo hy ~gen- 5 W des~lrn.dudi~g NASA,.~he :EnvimnJme]1JJtn] 110' f!i

s:

illi

IiU

Pnrroct:i,on A~~llCY, ,l'D:Jd MarbllFgiCt's OEfic:e~ ,of

Seienee <lind,'fechllOhngy .Policy (~T;P}. Blut Gerbe:rd:iliUiS ~aidI1CJ1.r1Ie on:~,e comments silii,e ~ww 'illirero "~:~!l1'\"':5Wp;pms." ~frmple" tOQ:ki ssue w g,th sp ecif~q; '¥Qrdiil1~:gon h~r~i~

]]illP:J!e:l!led to cmrooits,"'whi,ci:! 'we~:e:8l!11bm~:ted on ,M.m~,<ill1ly;.M,a:Ii'OOU~!rls sta,tement said ttm,t

mt1ike Slwe thi~ deesn "I: h:ii,:ppoo as,lllil ,:'

~ftbe ,gOa] W1]S to s'llp]Jre~ tJ.lei~[Le,. c:-!Jtt1n~ sj,vem.edi3, cov-e!I<Ii~ !ll1~estS tml~l.e ll,tlJempl

o:::rr'~rof

ctlines. food sc<!n:ity. and mental health. An

OISTP' otl'tc iiil says that the otrio~ "hadno pmib:tem'" ,,,,,':Dth>.ectkm:;; an illli:lcli(ll;IS di~ooses itt!!id 11~1!t waves brl!Jtn~~t '.~ d!o!,!jt hO\\f\vliiJ.aJl
NATIIJ RiAL IDISASTE,RS

seek 't.orodll,ct!:iect~.G\liIs.'" Oerlberding ~llys ~h~~ skepticlll ofthe OSTPllflWmml,~la:t OMIH; ~)' editing "'Vl1i::l h :uileO~srn-"y bec,n.l~ ofilll8l.l.'I'1dell!t t~j1,ete'rec(HlCn~ tile v<.i!!'ious CO!m'!IT'I!CrMts, c.-.:ml1!\g th[1'tt <jl!lSit
01!

osrr "didiWl

:fitil'~d.Geroerd~ng:i!.lYS !:lhe'dbe p:]em~~ ~J~le flllp aboul her teillt"iJi1lwny ,ie1ld\\1to .ewe talk ,{bou,tCDC"s role in ~1iUdiyill:g elimate ch.mg;e. oo[I~,git"i:l! sil\'er [inirhg~'jShe says She h~lri¢C1

hyp~l:hesiJs""

th

Shc'8allihil her filli'illf OOrt,,,,dC;'!.V Mo"g,::uJIiJ,iiii,Issue all the 11I':ap'furprUb1~CJ hoolt~l, ~z.pag~ difllfl: ;;g;i1dtlm,~ '!,f~tr'i!]g process "to, ar:ud I 'Ii.vin eomi]lt!c 1(\100 so" --mJllKlINnstlill

SA-IN 1b:IIEGO, fA.I!JIFORNIIA-One UffiIiSllitllg ~ro, ~u tiJewee1i::kmg b~tt[,e aJga:~lll5tr~~.ema;<;$ive

wildfilies: that de\'"d.SlflJted SloutlJa.ern Califwnia ~a:St:week W,f15 <ilm;lillliU<IIlUledP:Jr-eiCIllitof.8 air" l plane., origilmlly deSrnglllJcd ~:og.at~iler[llJteni~ gcume for the ~J.lilitllry: By :provid~ng fiIe:fi\glilt~ e;r8livi.th UI:H().-.!J:te~mi~tlru~e cli1'ltaon Ul;emany con1i1!!I!,mtiiO:lUls"it h€diPedin the 'OOor-dIiIl<l!li,OIl offin:fiJghting; effurts that SP,lIfOO nmny livea iJ.lilcli!Jtru,etnl!e S-~flC .Iudi!l'!ig th'e'i,re;lllcr,1I1d e PaI;Oi:'i'i.lU O'bserV;\'litof.il.

Genter ill Moffet:!: Held, v,ihrich d.e:v;eLIJpooi the 5eFa,m:r. lkTI.lomillill.'S, JilreaNl'lail4'i1uc ~Oltbil'" mation ]S .aruso ;1. w1lt,!i!.~i~.u:prQVe~~ ~,1ile],lt P:ilbted alliplaues: don1t flmave ~Jmis,eqiuip.e~lt and '(;11]11 O:[Ilylri1~.lS'" mit their d ..ta by iiirdlliOJ]s Of IMler
t!llleybnd. so sc\'e:rni.
bOlUS.

Qlficn

TI1:e p,hii'lCfi01.'lt flies for NASAiilim.d the US:,F"QOO~~ S r;lrvk~j' tlihtch have QuH1nedit wi,th s'Wtc-of..;th!:HYr~"lhe:itma:L-i:fl!fl'~fCd SCImoson;, to hc:l!pflr.efightc:rn decide v.ihere to do batl:lc, 'the 5,ycflr de:nmofl(ltrn;t:iomlpl'oj,ec.t'. dlilln:!tJcd rlduuna after the Nflt[ve American Chm::~wwo:rd for "aware" o:r "'~Uitellig,e·~t!" lmlll~i!lTh'nlilred hQt-,s~~ d!1i!~ ~o'a :!i:!l'~eni~e"Wi'dl,11l 15 :miIUJte;5tril:;C oomm:l!!nid. centers all 'ovc:r San I)'ego received Clo~:e]'~(loo.ed (ioo~e~M91~ • . ~m<lfl,e's 'l:hm:irId!]GlIlted Itli1ere:mper.ruru.re on the ~'otn1iclat di,ffel)ent:lcmal,fls. "The fire COhl:l~ manders love the data," :says ;i3lf:ooS]l[loe e'llgi.", neer Brent Coblern!il~,l. ,,¥J,lO h,;a.ds the pmjec.ot from NASA~s Dryden .Fli,ght R.esea,]X;h ee([Ire~r hl:s~de EmwarrlsAirfrnrce Base,

I:l<'lSHbefurlC:~r:e:figbl~rsreeei;ve it f "~n ii:l1ieil!lv.~roJmmelrn!t~.c ~{lutllliern l Ciiliwrni,~. wi,th ;"l:iry' 1~~gh t~ld:s w atKIfire-!l, iim:!IQving lfiiplidly. th~1L!i~ ignagcry car! bg; ,ol'!H;),f-d1~t'e ql;i!,i.~kly;' S~y8 H~nkh;y,.NASA ~~Iope~e:vc1l1lituaHy tralm!s:l:er d\J!a!t t~

c~ilily

to piloted planes,
j

,::)j

~ ,~
~
!~

'i_
:~

.~

The ~:est Senloe tor 40 ye1!lrs:lruiliS relied.

plnflLes. nat!l:S E\fCrct:l" 11]e~,ilWlestigatow amhe pr-oj'ed who '" :~ ~sbased ail t~;1C .rorcm ScIl;~OO~SftemgW S!l':,'M,~ ~ngApplicll;t:iCll~;8 Celrltcrin San Lake CU:y.
.~ Olill. il1\al;geslh:nt.1.p[]o,ted

i~ ,Iiinklcy;

Utah., m]d.!an!'lrepre:s~~~,~t~chr!o!~ogk~~[ st~p '~ up, he ~ayt,!;vi'dl a ~l(W~i S!:iimS(IIf~la!t c.;,,1,IJi],penc:· ~ tr~ue$~'!liikc:~!'ld elm,i~~fllC :spots b;t de~ct· d ~at nffi !~... ~I.lg. tnP(: .•.. ,e.'d.·_. em;:. 11"'. e.~~. s. S!~ ..I.J..as. 0.5. Q.~tl.p._' ra~~.:. .'. .• . to H)OOroC,"We ~n g.et ~rytmlt~ a~d hm;
, t,e:rm:tl"leralur,e d:!sorim[n!ltfOll from !!urfa"c!!:; W' e vel1ils," says, Vi:oot'IJnAITlb:ro~:ia. ru1kha:rna's, l~rJ]'ni. 'LIO :f:!j ci[pBll:rI\!'esti~mo:rat'NAS,A":. ...A:I1imJ~:Fteilear.cl,
,ill

i
a:

tc. _.. '

:~k~ml'ia'8; pllots sit lin .81tmile:r at NASA's [)rydelffil oCen1:er 1'0 Ibe IGI~U~ij9Itth,~: liJidijr~. lIil~rm~L-lii'l'II~~~E!r;Iima1i~sl[o,i'Iii tlil~ pl;:lJlloecan 'fly i:n'110 dcmse: !limo:!.::<€: IUlllirnilllned ikhal1la (in£'~) h~lfi'edll\1mfigM!1![s batJtl~ the P,tlmnacila pIUIl1(:so.r higJm !Il.llnds ,~il!llOllt:lUlt] fir~ ~earr 5..Ull' me!lQ.'~ fatoon!i3,r Ob:!:elV.attJ'~j', fMiJg ~lm:mv's rile ill dU1g,er. lk!1lJOJ8i CElilrn, (;male:i!l ~;mtspoU:b:r~lOul:S on end, tar elll::HI1I1I~ .Fortl!1!nflt,e~:r fo:rth e Ci,bservi!ltory, U'DIC '\~ one o:rt~lel8isU:ob:rea~. O'M:!:. pie, aJndftiy foo' as. W1Illffi~,y 3'11 heurs stni.g~,l~ i?bOMa,cha:fir,e U OlLssi.gm.nC;:~l1Il's would $ie'ite:re~y stress an '~lm.[JJt "'M ~il~.yotlin,~r fires hadteaehed tiitern-(llOl'Ic:h~~ Q\llibomtl, ,crew:I;k,h,UiI<I rnIi~ ib; f~,1Jtn~his over :S]Oilil".ruud support fmm <lOrDS s the :sta,w had (lJm,vecl;" :says KNdel .... ~:f\~~ad OOe::IiI1 fi:~str to h fires iIII .Aiu:gust.but the: desen fires tlla.t b~m.ed bfe<l,k Ol!llt. we~i::IhetalkiJ.l:g aibout 'lI:ViIlait a gl1et'Ut in S<IlnCHe~o COllntylut: we e:kput [tto 11 oou.:ghe:rtest '''E"'iierytb~lI1g;sh:api!J'eni!'li(!; ,I lot pla.cedl]SlUsed to be:' til:Sl:er,:" said .AmbJ.~~~<l (In Friday. 26 October, Wi.th the dM'W()r'!str.atiofl proj1ect comiJiill@; t11e third day O:fIk11,la!li'lS SooD.]~ m:llssj,cm. to <1.1.1 encl, rescerchers <Jj[ieiI:Uiai:tin~ word on Thin day, ~ifLcp~'1Irl!e flew O'i,l(>r tl1.c'coimli[l<l£ha \J f1!u1l!dii.Ji1Ilgre;(ijiI.U;;stte sustain theeffort, f~.'e:j~v~ic:l\! 'ea!mewiftlm j,lC\'CrailkilOM:Clro:rs Qf MOile)' !!!'lU'1Hile only hurdle, however, tl~Pak)!mar Ob~e~to$)'. O\i",~dii~d 0[Jr::r SUict ru!csa~()ut f1yi!lg u!lw~3in!ledairc;!'~ft ~~d by tile: C{t:n'fom~!l~t'I:l:~ru,t:e or7e!llh:llioro,)I; in prime !n~rioti;;a.I!ii~!'s,,<'!!eoOk~'ll~aflic~ :at tUM;;olb~!:'Vato!y's :five 'teli;;~("Q'~5 incll~d.c the ~:nllhth:ide iJ·f 7 km}inak~ it difHcuU to 50g,·~m "BIg .Eye .... Astro~ome!i W. SCQt't $eI;M:tre pernr:tiss,ipn for e~,ch nig~t. And Kflrd~I.~a spo:k:cspc:!'SQ!lfQr '~beob~r'\f"4t)[)ry NASA 1i mi~8io~~o d.twel,op tlmefict~ch~Qlowho ~~d t(l,ew!c~(1!t:e his OWliiJ,hQIll!;: nc~rby, g,k: s dQi;;SliiI ''I: CQV cU' resp~n.di ng to' mla!tr~:r.a I said!. i'~. dOll"1: :kIl()W or I!I fill': that's ev,cr bee~1 dIsasters. Til at puts :Hl:haJlut\;; fli,l!twre ,as ~ timls big .of i!.~nea,! hem." tlre:figh.tm up In thea:Ur.. ".'JONIfiOllillEN
i-

72"

Se,IE:

ESCOP'E

New S;~rul iny onWcltCcii I.e Tr,iia~

S:l,U1m1liiedb)l the dooSiol1 to ~QI~ta '.!.~[!elri(!l of g ~rCimi"lil'lg AlIOS 'vtIccim~ made D:lIMe.rrtlk 8. Co.,. iril 'Seiple IiJllbe\t '~c,iel'lce", 5 OctDber, p.. 2 al, l~e$9t1IITner~ :ne ,!ilQW' (iOOlhlOn:ling 11 miOre!i~a{]'k·' inngl prusiped .~Ull:1iJia.calillil.'1.et:i peQpl,e, !!!oll11le~aw IliTiIiI¥ ~i!lvehemrne n:J'CRrusceplliMe to HIli

Shllilfooo University,!;, Seul!iItg Kim was ll'>el.it~

~ng CilJIOerpad:ients,wheliili

IIUO'l~!siclJn't d

he first enceua-

~'Ji1ocmce ~il'l!mlin·~leyl1.eeded. the hJimcase and n1lJl:mIUiII cells, Ki ]111]."8 te,mril

The paltient::l, 8utrered from a rare ~l1lrn!e~ ited

sy:1!i dr(N"
C

teredil clue <'Ibout: the bio!lo,gy efdiabetes,

c al led M I~N :~, e r mu hi p h:

CJ1ldoc~rine ne;oplas]lJ.typ

e ~.wliuri'Ch tlr.igge!:~ flll~!Orsit:!e~lclocri~'!.c g]arJids, Jn some cases,

bc;t,rilICcll\lili1i! thepal'licl"eais muhip!y and 1000cr,·

t]r,Vggm !beta, ce1lproIH«1l,lioill in mdi(;'11I:t::;.,w:as what caascd merl~I1I1~'ve~,~,faU TJIg,is.S~ty~ to SoromJ(:r!@; sugg1CSlsa di8ti:ncnchf!l~rI of C·\'6"1l!tS( A OO(lS't: in prol~c~n ~YSC\l a drop illl menin,
\iiJ!J]c:hi]l!;c~~8 ~t~ c(.i~1nU!88. 'f~~d~~oo¥ery is~'quH~ different U~~n the ~:iYmlOf iiiIO!:Y," tJec~use liiIere: 'dle' liiIQnnalfum;:tkms ef menin '!:1lilce CiCm'l!l:' ~!lg(!. ay;s.S1iep~ool s M31fX of1r:l\tf) NSiliol181 ]ns:DULte of~)il!Ibc'l'es a.~d IJige:g1,iv,e >aJucli Kidney Diseases in Bet~l~,;hl" M!!lry~a:t'U4wbJ) helped ~e:adl:he teem ehatclened t~e .MEN.' ge~.le. liU. ooc<LlJ!1I.sethe'INOlik. is S i:11I miee, "it's har-dj~o c::ttrnJ'}o'" l:ale, too much" Kim c<lurn:o'l:ls,. The wo rk ngge sts MUlt mcniinmigliat bCCQ~]:lle a tool flJr d.cv,e,lopil:l,g hera co] lsin di 'Iib,ct,efi patients who tack, dl,ern. "Up until ,iiiibol1!t2'OO'41. Iliv'c:rybodiy Siitid tihii:t you c~~t

tblllrid 'dlOJ.tpro,lactin. ,ill hotl'l'iOne 1hii,tri,~es dWlrili1g ~;b'TIil;J!1;CY and 'ihfl,t: St't-eI'!~OJ!l hlltJ~ll1d

iIDIffCliolT~ha:nI p:artiap.al1!h who re reiVM a pl:a(eho.~pen15 (iC.lJlim!~h[l,t Ino Iil1!:!Wd!lI!t.a hll;'l/e I~m~!!d, simp1y.tll rnewinterprr~tO'!timii ofth~ S;'JIiI1@ f~~dlililg!s. .,!!I;1iI im~BpEm:le,rn iDi!~fIl,l'IclS.i!f(!l.yMoIiI~.tDliln~ [
BOiird (DSMB,)', required

klr celi1:alli'1~l!d!l.\ira[ ,~rlfli·

prodl.loo ]~18Y~i!il. T~ig rc.ind'cd Kim of

lh

11.

vcry d:iflicn;,Ht't -

state: 1J1Il::~,I;!~lCY;'her,c, ip!,OOelmt~ :sig,naIBand l

e bUl'!deu
0 t31

:lieh.lS lead to

il1ISI,llinlX'Si1l:m~'ce

a:ndademaJm;d

ca i. !Mla~s~reoom li1lIelllde-cI lD:ppi'ng the 3000· s Iperson tria~, uiil!der way fiii 1f'4(1rlJi ,and Somh Amlirac:a, itih'e-C'alfiiJb~!'I,. ,and AUSlu:ati~, ,af~eran !r<lU::rim aili~~~i~g:r ~aIHh~ Illii!rtk:ip~glls re~lled ~Iilat 19 ~p'le ~i1o II:1a'd re~,eil/e<dat I~g~ltwo

'rolimme henaone, An mllncky 4%, ofwome:n (laJlI~,ot plTIdm:e eIli01!J!l:l ifll:ld ml;: di>a£."Ilosedl with
~stfltiQl'lal dj,abete;s, On p... 806,. Kim. a d\(l'!,;e]~ ;ge OP1'Ull,cnt'i] hi o]ogi st.tind fuli:s

deses tdlhe~\I'I~(;ci!1e becaiTi!ei!1lrled~v~rsYls;

Sl~Jnfurdcolh~3gllf5, deseriae <I eonaection inmice between

menin ..Hle protein encoded by

the !JxlEN.l!ij)elle, and gestatienal d:iilbetes: .. Meliil.in m~d ~Oli1,g been k~lo"i'i.'n as a hl!ITIO'f'
~i!i.ppre:!l~OV~ M EN~' Occtiif:s \Vh~i1~hepj'1()tle~j] is tilc;king.

lllpoop~e'il'l pl!lcebo'gr()l;Ij). IBe;;:aJl!I$e vaociliile ha.dlfa.i led, a ~.rl,i;ll.afnhe same p:repara· tiOl'l in S,ooll~ Ahita 'wi!:5.,aiso sklppE!d" 1IlIlldlh~ [li5M'B ove.~eeimigllha:t st.udy su;gge~ed ~~t :~~earrh~rs;rmtii[Y'Wl.()cjlll1ltBci p~ple of ~e !po{~nliilli~irUlrel!!~edri!lklhE!Y nOi\! f.ate, aUhougfuI fne d~nBf\ena!' 'ii'i\[I Ii nllt sI:ati~kally signlificant. HW-e had t.",O D,.s;MB~ [(]ol'Jt:!dai!.ltle dialta ~at dif~rentl!i';'" 'Sil.:fli Lftiw.rerim Corey, 11 st~d~~&'Jder

me

me

NO\l,\'.K:iJ!l!!~~~dhi:'! 'COUG1!gue:s report tha:t inilrea.hhy :f!ini~~aJ~~.

geti:'imvoo1tt cet[slJromrep!i·, c1lti (l!~l;if YOI.'! [g~'e your beta (;'C'~~~.h)~ b\\'!;d:' srlys A]l,df,e·\V

W'~hlllf1' Urliwr~ty ofWashingtQIDI, .Sfa~:Ue. (olney $<lYstjher~ ",ere'''geo~olftica~. (olnsid'era· tionst lhilt LiIl'dllll~ Smllm Aif'rilG'lIii[il~5M8110 "err onlh~ slide Or$i31r~y." Swd!yorgfln~r~'m~. mee;l, ill! S~alltl~~IiI~l!!!I~~k.to, t:lcooly ro¥im th:e- data.
-mONI (JOHEN

m~llilli1\l;hibi~ ~llelrcplka1:iQn SllC\v,aID'r. an Clldo(dnollogisr at of beta ct:;U~. Oi~[~ulg it dO\!iJ11 the lI~liven::l~.ty ofPH~b~r~h in Sd~lgI"ply prl!)bl,~m. IIIi~lI~ililPt:nnsy lvania, The 'find. that allO\ii,IS beW!cd~s ~o:pmI iferaitl; 1in:0i, klOg beta elll~~sin irlQrm ill ~ i:!1.cm~o1Is.ingins,l!.I.!linslJ!WJy" .I;t:'~ III pm~g:ii1IalltIml(e expal"ld to m sst !iillppre:s s.]l1g men~ ninduees el ever lnsi gilt s.~y & Rob ert i!l:~ma.lfld '(t;opt blJit !l!Oit in m"iC~ b:et~ eell eN.pali1li!~~n~s"~IlC SOFe'I1i$OI1 o!ftlil;e UIli1'1.1'ersi~y ef smaU step ina ~,ong quest' !j'ji~ ttl :hig!'lc r l~'i,i'~ls @~ Illfl Gllli iii tLD '1LUlde:r.sU!1l;c! beta cell ~'ellH~ M'tJm.neool~. ]vUn11leapo~~s" wllio p,mnteilil (bGrt,t)m). studies: hmvthese m~]lsmla!pt~o eatien, ~><IIys Yuv'!IJl[)or, a p:reg~l8JI"tC'i: ".1.knew abolLlli muHip~ 'el~d\)c;ri:ne develepmental buo]ogis:t: 81 t~~.e Hebrew neopl3Jsi<l 'mryeafs: ~d yea.rs,. .. , but :~ne\'e;r U nive~."si.ty_:H.ilIda:!>SiilhMe di Cl<l~.s: choolilJ]1 th(llIg~lt3Jbout ~~lll:l;i:1:Ig i~ r:rorclgmmcy:" ,~fils· J"e~,·m><li,enl. lsrnel:. Adlm iHed]y, dillyis in Ii! a to ro] e .bo[ds lip ~Il Ila;l]m3,lls. ~,l,lenin l~,my ol:l.'c~r ~leni.n·.b:El5ed thel.'apy COll[d be comp'~e:x" dtles atu:)l!]I~s,t1donill dblbetcg .miI,d ways the Iil>ec<uuse,it .,i,~,htintedbw wit.m.1 m:elmiin's m]e betace:lb [iegen~lIOC:. IIJ~. <lmmol' sUI~p:r-e:Ml()(f. Kj[lf~ gmup first'exmni:mtCd liM:IDlit Jm:p~m. M~i:IiIN reJev.:l!nceto, g~tati!()llal d~betes ::;: tc :menin ffilring pregm~im:jr;.[Ji1, nOliiluai, mioe, ~-e~l:I1IJllirnsullU:detl!r~ SOJiI.1!estudies :!RJ~e.st that

FnerIJt:1iiJ SM' 1CmIPS;IHaI~led

.rAlIIS-Frenchl Pre'lid:erut Nirn'~iiIS 5arlOO:zy de~ig:ntBd emkoollllBI'lti! ~. activisls l:asl~e[;: lfu;i <J,nll'lol:lm:in'9a mOlf,atmiulm OIl tine ((mm:mia~ witi'llatioln of g;eJI,!2ItkaUymadiifi~ (QMJ (fOP!!;. i5 of swe~~· The:'~lllI1pordry:fualn 1i\I'il!l (!'Irl!!in ill

t,m

lIDI!J1 ~itvira!i'iIlriOOiltlil

glo~i(i~s amli

OUlllcded

acllhl~

end of 112.-rlillY mtJlndt':ib!l~ It:lile~imtg all ~h!!emil:Iroliimemttlile:r,~,S;arkmy ~amdh~ mJlt)itQ StiiSpend olJi~~"I1!'i:icl1l!J1r MOlilSiflni.o ;810, a!liJilsect.,,~~tS:ta,f1t: ,1TIlI1i11:ean:J 1ihe:orniy GMcmp tm.rmtly g~m~lII'l1inl

fra

nC~j

llimila nm ~High Al:lthmmy" ba,'S b~oo

b1J,ok ~p :aRm- (he .~ aJIIJimaJ ,~~ws biliiil. Totcstw~~~l~r thisw<l8 z

5 Il'.enin lc:v-els m.op <lim clim,b

w-onlcn ,,,<ho'are d~~.10sedl;vil~gestatilollal

~ di'iving beta ci(l~1CXI~~~lS~Qli\ Jm and bh;. >oo~I}· K !Z 'i ~<'IS:1!I!CSct\(la,'f(;d,lra,mhi5;~nic li!iIIicc. \"ihQ~ men]ll ..,; prod!i;lcti.oi1 didin't d~cl~e d_ing l'i!X:gll~i)Cy; ~~\illhC:Jl nl.~e mice beCaIllC:p~a]lt,dleif 1:;: .gi,lj. :~ oOSJt;;rose ro ~C¥el:s {:(]~~rob:~(:; tQ ~~o~i~ ~~ g t,uiQnal dh~b~h~g, Atltopsiefi OQllfn.nned th1U, :ij \\lhen men:iw didn't fade h~.pl:cg,um::y, beta ;t5 cd] pro:nfel:.~ldoll was iIIli1I<1f.1:,e~ amI tile a~mi~

OifLee'I~.ey~ro~~!ia!m. saysThomas Bl!:C~'mI!.all,

dime~g liWiay ha\IC; had ~Il~ldm dotl!clm b~fQ!I.'e [Jlregnai!lJcy. ;<¥ou haJppc.n toiwoore(l;pt UlC!n"

~n c!1do~]~t)logi:5t !llt: llJ~ive:r.sily of $outll!· enil, Cali!Qr]i)Ji.f1iulL.Q!; A~,gck:sl' \li~t) d()~bt~ ~!~:{It mC!'l~nis '':ai!lim,portf!nl:: cO!'iltrih~()r'~ i~
~~~n gestatilOll02.I.di:S!be~es.,Sti~ill.iliat·~some>flDUil:IINI

too

n1il'lg, $ci~nti$ts ~n 't ]\;nO'lIlJ lmtilthey a:ssess

~uellilmi~llpeop]e."'JEiNINIIFER

set IllP lC!l weigh its n'Sk.s "'mJd advl!lLflitages. hllrnpgBi{), ;'i1F! ilfidlJstry k!bby group, ..S<Q~id the' p~alil! vi{!~a1les frt!~Iif! rules:;aspo~pers.on ri(ITi~he ~l,nqll'eafl CmnmiSS!offii ((l1~lijr!lliis ~IhQi~ {olJInll"~!s.Clli1IiiiCilt ban tfuielE~roi~e~fI Uniol'lr d'PlI:lrCl'Ved~tlrann but sa:is, that ~hemiTl'llfl1i~S'§iiOOli!l ,;mi~,'Ii'I!;! detlli'~ And:~ (hol[!l~l!:a, a boaud .!iti eDf1:bef o~ 'industry group IFra tmC~Bial.edh., saw~!h e ,a,u1llil0rilycoo'ld ihetp' i'nject more .!>Cil&mell!i}tol 'lne GM d1ebalte, af1di~ 'it I~u~e!>on 1:1 :lLOIberi(llfe the Ine~. pLa tmrtillilgl5ie\!l5(iln~the b[lil1'~ iIlllpacl ('oll~d ibe millll~mi!l~. ~ARI1IN IENISE.RINI

729'

NIEWS OF THE WEEK

u.s.

DEFENSIE

B·~ [)GET

us. <ICt1ld.elTll1iclobbyIis;ts
[}ep~rtme~JJiJ:t ofVefense

have long 'Urged the (.DOD) to boost i.t~

complete

aetion on ~lilii.:s:r~mr'sequest :~hr r

$:1'Il.:~billien

OO\le~cllt in sciem::JC and~eclmol~'}' {:S&T}

to enha.:lilice, the nation's strategic i1:liId eOQ~ j;'iomi,c cO:nilpetiti'iene!'ii~' .. But ~.It~lmlshthe

fOF die pr~iflI.mlj. Ai~ the tqpof'iom:~g.s .~ilst is til :$3<00' nI~~]~O:IJi i]1lj\leSih,~.lent: :in rtlIJiIlMt~.OJ1~~. sciences, cO'!.!'eri][l,gii.teil:S SIJic,h ilisbiusenSiOJs, pho'loo]~; ,ctr.;-

research spendi.ng (Sci(N~C-.e,. 2: I.October 2:005,1'1.423). Adds Alain ShllffeF. OUilC of Ycmillgl1 se III ier eJOecl..lti,,-es: '''Wc'r-e not gcttin,gtille

geL

Yes. ~1m;ej:'e<lire a lat of dai:milJll,tsroif do~h.~nl,But tlrne~c's ii1groiJ..nm.&1r1i'CII.of :S1J.l~:,pcrt fO'lf theidlea.'''
N(Jnc~l~.e:ii~.

same; type ofpnsJrub<l.ckwe used: to

Ol\gJency's averill! S&T pOlH:oli<t1 ~1I~~ r(I\!ffl modesny since 2002, g fiIJ.ndingfov b~8~C rcsl;)<I:lfcfuI hflS stagnat e d. Now. lnan u npre-

I!ils:kre~anh.

everybody 1!drfl~tN

Ail,pIi!!!d' r~Ji~ar(h
Jlfhl'<lna!d
1i!!(iltllll!ll,l.Gg¥ (I{!jji\l!lop!llli!ni

Ik.ttthc poop()sed~~crca!(jic: fa.c~s a

ItIjghurdlc" "Tile OOlTlillini'ments~lC dcpO'!rt~lcnt !mas made el'!.tcnd

eedented step, the Pe1'llta:g,on's;

re:8~~!i!clii Ibo~sig s(;~k[ng en I ~!%
]!Il(lr(':as~i~

DOD's; 8&'f budget

Ibr the nextli[l<:a1 yeSir:. 'Qh!l!cnlers say the; :mque~.t. whh:::ilIPe:IWla!;,Q!ImJ eize, improves

$lays LO[C'I!)TllO"VSQWJ On~le LexIot..!l r:e5e'lIIP:h:,.

Id~tl! t~l11rn evallg.atlilln, Ibud,get

f~r b~Y(HHlIav,S!i'~~bk re~aU!r'c~s."

""r:n·cialsa,p,eiiu· e~!.l:.e:ro, p1!1b~rut

the :1.Oug:~NInlill :more de:fe:lm,se·~

iI~gton lust:! tute, !I.Ws!!l~I.'i~~.gl!On,.

nC-ib:3!sednon:pl!Ol·il:.

'1"011" CX~tn-

pie. he S!I!)"St tI~ AirParre u!l:gielldy ]l;oods 32 J .f~21 iI'i,ghtl:!t !lir{\l'~,n, l1l b pros[fIiC!ci:s fOIi reklltedIJe:sea:ooh des[phe thecOIII~ Sl!lla.Ue~ sl1ver~. S pemdlilii.gl o'llsl;,h,mtt andl tedllil,oI09V Ihi:lt5if1't !Qlrcli~n<110 fa£l iI.~lhe "there s note'l1lOl,lgh IIIQney in ~he i tinued cost of'Ul,C wars in .h:a.q rest oflh:e 1i1i1.i~il<llny'~eesea ~1CIh,Cle:veloprnll'tlllt, tiesting,. amid e'i,la~uat~ol1lfmclge1 .• 21009 P'l'1}]]@sed~dget to purchase and Afg~l<1nistan, even half" tll,I,! JiDJliImbelJ'." "'WJ!a'8it The p:ropo sal. e OI.UCs,t~~iom ]'0 ~Hl,"fij:omlg, the, senfices. WiIJl"U ri~,n: now is: muh,mre. ]1,oi MI~ls" and tJia:e OU1IPutfull;g scieaces ..ThanepreC direc~:orof DeitellseiRcs;einrch and En~i:neer~ sents !I. 20% ~~ike:iIlthe agelmcy1s $l.:5bMmolJi :sciel!il.ce,~·he says .. A ,coJJil~liess;iom.d s~aler .<lgr0e5 thar [I. i1Jig irIwg (DRE). lu iii 2-4 An:1~lls'tme:mo to Def'e'[l'Se btlsiclie.seaJicblnullet."Wc are'I~I!ea!icd to:see reseaeeh iIJo,ost [I(':XJt ,e<lr]s un]~ke:ly. "Just timi s clJi scussi O~1.,occm:riQ!i!:withi:n~he h~g'ier Secrct!llty Robert Ga te S'. 'i\' l:Iiichl\e C ently ooc~se Mr. (~illie!ias~dfo[t~.lcpmpo§l] <J]iI,di levels of the ~eutag!(Jn;' s1il.ys:M. Mlaitthew became pu b lie, YOru.~l,gw<!IJms that tile Ow,ells of the Afii8ociati,ckll ofAnlerilcall UllI!i..M!r;¥olJ~ produ.Qed it dees net mskeit a slam ~erIlCY'S S&T~:m,IEHHmerH"liIIlI.lily beinadeViruitie·.\1.:iJidding that too ]JIll: director ha:!Jli!I't dl1~1:k," he sa:r~. Ilill!t he believes dlatt the plan q,1!I:1l'teto mee,t dl~ impos;in:g ~ecuri~ thretlits aJ~:kJaW forsi.iJch a h]l1:~~'i roectlt hi:story~ "~'We ,rcpiil1iiS the g!ifou~dfolf bigg)ct increases tih;at e~i1i~]e:n:g.e the ~l\i!tiOli." Citing Huemod~ erni;Uliti.m ofCbi:na's rni~itary. t]l;(i deeliimC ili!l ~1:J flie·t(.acl. Lobbyi~ ~~~O liiI.oteihtiit"iiollitl,S o1Iireoili,limisti.c ~~tit: will ha.ve80iiillU} im:pii.cl '~ '!,!l~r:,_ '~".C-".~1t."· b;Th8~C research by Q"rpo:r1,1:tio,!'g8!.~md the O!l fl~ ' s .I¥ ~n9 b,Y""l:<~' , \! _ i~ ~\iVd~ing oo~,g~~~~md t!Ppw!!''',d hJb~QM1~ ~!lJ,cro~i!ngoop:hi$dc~.til()jl olfreffiOdst o:rga~iSlOOf,etaxy fu[~Qql!i5iti()~. S\~PP0nCflilp" lnt to 1f!c;faCl~~:!l!1 d~c: me :ft~DCy's ~!~ldJer zatinns, 'Yb1!Il)g.prop('!Is·es e:stalbli:sh]n.g we\'\f .elllQ ~s reqaesred by Oa~esj,iii me:mbCT of k:.ctmology, .s!lldll~gi:$t~C:St~"'~lich \vould .g[ve S& T ] ui t~~H'1ICS.\'\fIO.fd~ $1 ,2: b~~~ ~Il lon the (i! hi a:liQ~~[ Acadcm[,espa~lc:1 d~!~til 2005 t him over~i.ght: ora Sl57 bnl~(l~blldgJet th:a:t 2009fi.:>cnl Y'ear CFY ~I. C01lil,grcs~ ~~,fIt>yet to cal~Clc]for a 1O!'~ lncrease in basic defense im::lltdes .DRE EYUDIiII111IJ'11l1il!AnAt:HM.lEE
CLIIIMATE

CHANGE

Ca 1IIIlorni,8 Sli rs 8$600 IMlii11!liom Pot 011 Soliuti 0 ns

Cali fbunia rese,mihem; couM :SOQiIl be aillille to ~~pa l~ye:<lf~ 3:600 nl]UiQiIJi c,li:ma~e:ilraitiative.

Th.e pr~ecl wou~d1 C~<lite t~,le Cal:irom~ ...Jmti.·~ ]:I.[te fuin' C[u~na:te SOIUUtHliS ~Q toSi:eII' n:~se<lln::~ml
s (I Ul,c st<lltr: ca~ll.meet s,tiic:;tgr'CC:::I1Ilholl:seFIS' ~ emissions limilS C'J1I1'tCtedi Q,ve.rtoo pa.s~ 2; yetl!l'S.

:mir~scJebehind. the: cUm!lt:~cha!nge laws," OIll3:ryag]rnli.:. a chen,is~: <It UC L()~Ang;cles:, who\!mrks: en mrue:r.Ua~s capable of sc:::p:rnting carbon d:iQ!{~d:e fronl poweli"pl.lIIll emissions, llkesthe [clef! tllmtllt utility co.mis:s;ioners are
paY~lg
Ol.ttellilih.OlmI

.~ meet it.!> mtewgroe.lThhouse ~s: em[s..",inl1stalldm.'d:s.Hu:fi:r:sl sland.a:Ji(:I. enactedlast ye<l!r,.

requhcs

iii.

:251% reduetien in greeahouse

gills ,e~lilis~oll1is. 1990 ~evels. by 20:2,0".1\\1\0 to

remere tlm.l1iIj~§1~leiflld!!lsITy's

The pl)CcsideJl1lt of the state's iwmb]~cuti[itiles cm.nmi.ss;io(1Ji (Puq., Mic];gld. ,Pee:vey,:rocclltly annol!ulIced that PVC is lonking O'I!t the pea,o~din&til1u~(,'l fIB O1i\vay~O ~~r;;~p'mc>IJt ~ew t1iu:(l :!~rg,C:IS:..lhceio~'liss~~~ ]S \ve:igh~"g ap]a:o to nl1ane~iI;thmugh 3i S ~'''''''I-t:n.Oil'!Idl :i1!ikri:: in cleotn'idty rates.

bot.ilO:m line. "ID·.rem~yhill!p;pyro ][ea:.rdleP'UC iSirlking the ~niliMiveOI.l~IUs"·Yaghi :says. The ins:ti'hHe:~ d)csi\g!Tl~:Sstill influx .. Ill.lil Kammllri mid otht'lfS sa:yit~ Hkeli:rlo fO(aJ:S Olil

rong~~fp[Oject'S tha,t:'ol~~1I"noor ..tc~'n. C:!l!i~ g;'l;ving.s. A p!le]~m~li1:ai~t ~t, KaMmC:iWsay~, ~~

O\l!

yean). lI!§O. Govemor Arnold &;h\-W1~zenegg;er signed u. executive :t:H.d·eT~<Irset]ng 810 % redl!l.Citio:ns: by 205'0. The [Ieov :i~tit:ta:teis not e}qJecled~oIim:CI Jre'l!V bll:i.ldiQs. K;ammcil sa,~1'l,. b~t ratim;cr \v1.U '" ~ B!!lpport ~l1d .cxWlld "~1<!.i.~i!l1g camrru~ roa~[I£IC:h ffi ~tl~ns acr,008the i<taw. "'COOrd:m~iti()i!l l;;: key ~ hero." ~lYS EllcI:iA~nti. e~1!Q;d¥"(l:di~cttJr for ~
, _ .' 6:!

.KJ'!~!l'I!~-n,. Cll~y ~n

"This

is~~[~{

e.'l\eiting t'Q see," sa.~s[)ani¢1 po~!~c;y xpg1 if~dle tr~i··· tio~~;;!!!ldgre~ 'bl;![~dings" ~d ~ [JoUc.)' octU:er e
no nl'C:s:I1ICai~]lbnilifl'5 d.fJll~re,n;:gJiIll.f!t:iQns; w:i~h ~:Iitosc (If ot1'ncr stales and C{).uno:ieos. Caii:ifo]'l]ll;fJJ nelCdstedll:lol!Og;lca:~ <JJd\i'\ElJllDeS

indudci! rese'arehcCJ1JH;tr~, foli' efiier.g~ c:flHc~.c:rtJcy. SQlidL.sta!t;:: lightif:l~ca.:rfbOll $~1li~[;lTa,"

,~er:1lH.y Qf<Cal:ifbrllia {UC} • .B:e!l"kel1cyj wllil.o vic'!.vs ~hchilis;nHlIJteasS! '!i~y to hnslla~ Q~[]n:ate gOfl,]S; to iIl:OtUOl.1,. It wi.11re!lJty put fimulc! al «

dlent A pub]~c CO~l1:~ellt per;i,pd (l~oses !le;l(,i i! v"-:~'k t'..,:~l!r-w~·d' ~::!ru co.,_.~ "-aritJ :'ll'xt· """ >Ir .,'I f ~ .',."'" .• ~"L,Y 1;,<, n Ili!y . ~'''ri:nr''s ,,'-k~' .. reL :I ~[~gO'l}5 $i1l100dilly. 'tiThe ]nst~tute CQ!,dd have 8 m.oI~ICjI~O spend by nei."il SUIllIiill.cr, ~
""R6:I!:ERf F~SEIH:VllfiE f!i
IiU

rel'careh policy

all

UC 'g om~l(;;of Ole Pr~~- ~

'.c,..

-...,,:lli

Se,IE:

ESCOP'E

AIDS RIESEAllilCIH

R:ecoElls:III',ucfing 'the 'Or'iglins ,of theAIIDS Ep,i,demlic Fr'om ,Archiiivad HIV 111501,al'I',&
Five HIVi~I<I!tes th<1ithad beeli1,forgotteniilrn, Ih:ezers fo~~2 decades <I,Fe, :rew-euling IIiJ,ew delili Is t100"ll]l ho,,"v <1irid ''I!'liCri &e ",ilia!! :spft:<id from Africa to Hil,iti <i1Il1d~,~ene:l';;ph)ded OJrn, t dl,e world scene . .Evo]nt~QrHI,ry b~ologifl't
Ot.liI,el" AJDS tesearehers CCilJlliIter that the ~l1obe:r ·pi<lpenJff'er.s t~le ck:ilregt picttll:e: yet OIrhO'!~·the yonwli!; epidietllic 1l1<lltur:edi.":lt'!i! it
111C!e piece ,(lfe,d~I;t;iQli1:~rys;lelilthi~g,:' Beatrice Hilhlfil'. a "irol,o.gi~S!i atdlc Umversityef' A]~ba!rrH.!, .Binra.'1i,~ghnrn, lliJId ,1 coiUlirt'!O!' ofd)C; 'Ko:llbet study, One prmiQc:att\'C

ChiirUI Wants lMior'e' EllIv'jiros.. ,

IBEI~ ING-At Lar;lliTlr:dh's (I()mlrrnUl~istPCirl.y Congress, Ch,]!fHI's. leaders E:',r1snril'ledIBmr1i[OI'lIriI1!elilti!lllpmletJl,iiDn.il:! &:e OOUI1i~~~S mmlstijtu· lion. Now' Chllm1!'s State Ernoiimnmenttl~ Pirote(~ lion .Mll"rnnll1i sl:rill.liOrIJ (S:EPA} ha.sinikeiJ iii de;am to train gril'i.:~!rOO~'.i (OImSBrllatiollisK S ElPA' s I( 1iI~ln<l Enllh'olluli'i'mtall Cu[l~re Prmnotio:n Al;stKi'11IltjOIlil o1IlndlRar~,fI mliIselrvatioll1 g'mWipin, Arlilligwn, Virgi'rlia, vr1ll~tflllpiI Itni!d!diflg Chinese UllilS~[VII' Uornstsin~echl1iqu~llKfuI .:ISfe$J:iva~s and !puppli!tJry~lh,fJt ,all'l stir I~UMic ifllte-res,tand 'P ride II!'! bl:Cld~'ers:llyi!11 Qr'd1er kl"t~,a,"!:siat.e lkflO'".rde·dge flilto ~le~.s!(lfi m e,gifl~iiiglfl,l~, a~, change., ~says EJretl JI~n 1(;'5. pf['stdeLi'lt of l1:ilf€. SOltnhwest ~(iresl:~y IU:iilil,ilers~ty ~!1IKYlilfi!lililg City
iDi!

very
~y~

Mic:h.tcl, W,,~.·Qbcy ofdlMil Ul!iiii;ve:l1!ityofAfi~ zona in Tucson ledths l!!,(jl:\l,f 8hJ!dy. wh~c~

<:l:Mlyz:cd HJV s~ved~~rlO•. ~~¥e H<')!i'l:ialiil

AWDS iPf!tie:::rli~ 'I:roated jfill M i~~i in 1982 <'!nd 1983. ··[t wa s the uex t b~!H thing~o Ibe~!lg able, to 'lmvel bftcik ~~l t'im~le~," s;aIjlS WOlrobey., who oblailncd tl~e SifIJlllp_ ••

:lcsthl:~l,Ig_ hthe: us. O;:;ntcr,s for Dlsease C(:l[ltIJO~, :i1l1d!PrevCi:mJtioll

(CDC) ~n A,Uiilillta, Gem:gi<l!"

l",_I!I'._,.J I

_I r~~~II-lli~"'~""~'!l:I}I-~i-~;~~
f~ndilmig. Sia!)11'l Ha:hn, Siu=esti;1,I!~f~al~~Ol!g!fu1 t

several dtffcrent ~$iOhrte8 ,of S1!4btlt!P:(; .Bc~n~

.1ro·WIiI.hll~~tibJtthe United Slat~~

oot~onegot a

~Uli:i!

';"~"""

-~=~ ..
.....

I~,~)(tye~r

Chil"l~,wiiU heliJ] l.aul"I(h projects at :J!.JO site's: •. !i!1!I)s:t ~ik~ly lm!s{)~e' gf (hilil1l'~
~RlliClil!ARIDSlONE. '1(11

IroU 91~1.y2\[)OO ~:[lll)lre reserv:e$"

In a paper :pulb~.i~hedonl.i[lelh.]s week in the Ar:JC(!~¥iil1g.f! (JltJut N(J~iOtl,{iIAcn,demyof .sG'ienCl1',s. 'WOf>ooey alui, ,oo',\lfOimeJl> tbcm>edi ol1lwhat"s, known <15 .~IlV~I. su/btype . B.''T~~is

~~-

,.,.AI d H'ea ds

th,e

M'inI'I:JrIJ

was the

YilT.imn

that led

110th e d~gCOI'ilel~yof

A]1ClSru-ad so Muth ofthes,tQf)' d~,1Ltreasedits

~~eild a.ftel" ] 98 W says\Voro'bey, ,'., Mm::h oonilii"Ove~~1iy bIT!> Slll'idcj,ja:roU!mi. the ori;ins ofti1e AI, I)S epidemic . Beeause some

first A]DS C<'I~CS ~1!I:rf!.liCedin Hla:it~,illm: i!mm:i.,g~,aiit~ tilitii6 Uimlited S~at~;s., to CIIlC-,t"O tU1C e()inS,'Ilefl'lfl!tio~1I! ofmall!y~c:nl,ee ihel~dii:d Hi'!i:ti,i1!~TIias aspecial ri8k gr®p. SQimcpromi~ nent HaJhi<l~ rej:i~~dll;;n1 have rejected the ud:ea tfutSit t~,(:virus spre:adrn-01lilrn~hd'l'i to the
OftlmiC

The fi~st ~ipg(ec~aRLQUi1c~r!id b~YCi"idIEaJfllh 0[b:11 bV aelewl.oljijang ila.tkm l:s'Oi"iitsWffj Hi ·th~ mggflJ, Cht:l!n~'€!' t liI~ii1'!eg:fQrthe- !C:hifles~ g·ocIdes.:s ~~Olnewtollhe mQO!i!,Ii\'~UQ~i!ii\l\e ~'fr! hmar o~bit. 5 Novl:!IT1i:1e-r, 24 Octobe~ The: l~ilUHii!ch rew ~aD"ge(rowds neg ~the 9kh l!a fl d 1~~lJIliilclm (e!IiI~errFwa$ bmQld\ca$'t l~ve'on ngtiona~
tiE!le~:sioliil. ~:I'!dlp,mmpted se,nio:r (h~lnlese

oflkilllls. t~ d eci.are l!liamlS roshare 'w~led sdence data, The! .2 3 m}·ll::gl5:atE'~li~!lilll~~ dude fhe meen fair a year amid :!lefld b<ldclh rsediIlllJ~~ionallllil1la~ e~ o~ t~ e ~lJl1aJr smrac:e ,amiCI <I1f1 <IlfI<I,I.y.!ii ... Clir moon dust, Indlaand ~he M'rili~er:l Srn~ pltln to [1a.ulIlch InIl oon ~biflien :riIe:xt year, ,and )a Ala!iil illlilllfOU ('Ked lli1~s wlile~ fhat it.wi!~~.l<I.um:hiii ml:mtlk Irl:l¥er ~I'Ithe

U!l~ood:State:s, contCllJd]n.gdil~t it likeoly

o~:'irurn"dl.recti,oo.

:t'l'1,Cfy,e,d

il!JJ~l(:

Mo.]euiLllar analyse!; Qiftl:~ a.reiliWll i:sola,t~ o~~llI":inlledearlier r~ports U\a!t s;!,1ib~pe !BlraJv~ c[edF'1i01l1I Cie:nlr;\ll[A:!h~ to HaHi mJbout .~. 966. entc:::riw_gtheUlrlHe:d SlEites J ye91's, kIlter. 11m researeh ers' estimated j)lfO!biSibi ~~tytlli,aJt the '~lms instead h'ave.!ed the Ulrnii.iool States t"ol~.I.ai1:]-'O.00003-i:s :int~;n] tesimal, "The ],],letlffilom alIe bell,UJ~,ful,lID.l(llhe a:lliIlysi si s e]e~ '~' g<lutr," ~ys 'B~~c '~Qfber, m.l,iJrunMno~qg~st m .~ Los Alam,os Nat]O]Jl(JJll<liborat:ory ~Il New

'lI;ff IilJliV'. A. new ~liIilal~y$~iClt 5~ore~: blllllo.~ i 5aflillpk!s homl eal~wA liDS pat~!li~s ~hOl'J~ IH:ait~1 Ja~n) ~ as iilst~pp~lIIgsto~e betwe,errl '08I1ilr.alAfriGli1IiIld ~e:1 ~11!:'!i~ of~he w®~~d,
Di@!>I[E!nt

.&-0.

:~ .Me'Ki(':o.\,,.rhopuhlishedis~m]'bf ]'e'sllhs, hll :9 Sciena1i~,2ijOO{91un.e,p. r789}. .~ SO~,lle:1IIlie p:~1.Iadecl. JI~4lJ.t"BiLl" P"pe-. not
.~who hea;dslhe b[uge.'ltAlDSf(}:S~[ich IJw,b'Tml:1 00Haiti, ~ys WDro~ey a~:dI o"\wrker~si,mplY o ''r'''~ at; proJu u':s ~dl! . oed 'clades -, :~!;l.o, t- .. "cre __ .. !~_r:;". _HilL'.~ ee'_~
l~ 'YI

'~ P.wpCllot~~ thaIt th.ti;3JU!~lO:!'fi ~() dc~~ih~ ctl~r ::!l abou~the:sexi,j:8!l ~USOO'ft(;~ of~lefive~hu'U£~
~~i~ll.N.igra:nt5'. who be ,C(l'~ll:c:nds QQlta]d hlt'lve :~ b~~~ Cl:!fle~lled by Amc:!"icO;lJrls. He f!i8Q! q~e!).~ dons; '~etl:lI;:r l:UV ,amvCldi!l1il. 1966,poi:llit~lg :; tOfletl:ospecUve st:t!JJd~e:s~nl~laitJ[hat: did not
:t5ffimff mil

fholihokl, it ~md not evolved wa;ys to tr:;lnsm:lt ~1~JOJJe ·e:l'ld;u]y,. SR;r:!!i o'rober,3.mtd ~ W 3~'pClar.s ~o ~~:fIve,beelml "hlcky" to-have spread ;fIImong ~lligh=.I.~skImllu]ati.olls-:pl:i:lm:r.ily~ W1Ymales m~u:: Un~tedSmte$" ~Ulen:spread!to >Caillada, S(m~,~,AlIm~emc~ E-urope,As~,. aad even hack to Afr.ioa '(see- figl.u:e). A~,ulle~Mje;ke Vandlllmme, II mo[,ec-ul.<Iir epi.diem]o~;og]5t ttl due ReS<llnst[tl~t'e:rot MGdiciI[ Rlesearchi~1L l.eUvell. Belgi~ml.a['ld oO""iiiluthor of!] 2003 srudymllt arri:vled aJ si,mi.I.~r cone]llsi()i~.:S, $,ayfil.the nC!'M work. undelfSiCO:iCS afU!odame['ltal fea.'l:J.I:ro ,orlUV c;pidemio'~o:gy. M08:t: of the cady tsok!tcs f(l!in.liIDdinlbiti~n~ ~~~ie~'~y "di~d, Ol!!!l," :sh~ ~,01c~. "VtHI

OCtHlins

Are~INijckell~nd.,Dlinledi

liiIIIQNOi!:l!iIi..tJ-A dozen marine sdentl1st5 gall~· ered here !a~;l eek at ili e befule~;t ~ tim e lnterw o IriI,al]ontil l5eabed Authonityru d'~sigril s,dif'"' g uard"l a.gail'lst. tille ,i31ntidpalied ,damage hUJilil ~heilll:l~ ~rill~ hl0i3rve~till(g or polaroo·s;izec:l nodII!des ricful ijll1n;icke~. "Illd oop,p~ sit1!.im!QI .cI1 !parol: '01'1 of !:he We.s:lern Pildrk sea noor with grB1lt bio~
l

d·iwmit.y. ~IPrralttk~l~:few~ frildivndl~iill~ [Olrgililll'· 15:",,] l'5ilil Il~ ~~~i:~5, ", !illi~d .,rue;::II), ROg(l1fS ,of ~~e ,roologki1l~. S()cietyof ILon,aolii. ihe !'ldemi· U)1:5. in~iIlr~ed1 aJ Rl'a~dmrr(mK IJ!r nlflle:400'~~flil~bV·

~~,ed a:r.I c~nt

that litI(;:H,)Sti; the

Ams

ca:se ml.1!H 1.978 ..

tl"411&mi~sio!l!ll~nd the cpi~lUicHIk.elO Qfi1~"~~ a d~i8 (;1:!1l1C. Vall!d<lm~e ~mr,"j the pr,omis>cvity (lif' gary mt}ll. appe ar~ h~' l!JiIDrvebOOi~ te d the [nIfeVallCflCeabove <'!I thN~ sho kl. t~~lda] ~O\'ved tlmJe'Vim:!; ~D lIu~",e.~ON (OIilIENI

4'O(H,ID prote"!Cbi:d ore-as, in IJellli'~~n 1m]li1ing in anamlllile.adyihe si~' o[ AU5:1lri'l:Ua. H,aw~dl1gi:5lfxpec~e-dl LO :s.t:ulwiithin ,aJ (j'OO1!de.If adlop~d, ,as €.iC~ocred. 'l~e r~t.!1i!c"" li~~~~l.!i~d~e th e first sIKh ~i3!ftcruQIF~e5 w in
tlailllHi

i~U:FliIi'!ti~n~l wa!tE:~S.

-(HRISWP~HfJIRPA!LA

NEW!i,OFTHEWEEK

S,cien!tiisls F'ele Chlina's SUlp,reme Pollymsllh

S,HIANGIiiAI:"""h,l tlm:e c-:Ellrly l7tlilC:f(lltury. tlilis hUl1IiIanist and c-XJleritnlelllt1l1ist ~H:,I[lJed avert glmi<il!b;oliiin Chi1~JlIby d~SSie~,nmaltm.g hlillrd~~r
crops: mild d!e'\rised d~lInlS<Ind ,e;a;nalsfar [rri,g<I.~
,0000liib;,oill. He I:aL~llchecl ii, decadelong 'eftbl1 'to g,mptmrethe ,1lCCIIt!liCY 'of the

hO'lil OiI:l1idflood

Ch inese c,aEeTid ar by ~,Il!cQT[Jorlil!ti a mere ng PlfGdse k!lo'!;¥,~ooge1iJt' oeletlti,ll'l :gp;o*J;;try;Hi~

ofthe hea.ve~s;,"S<liys Peter Ri.dbt:el~ £I ttii!ooire;t]u" cal ~l)is~c:is.f a:tll1eU]lii;vejrs~lt)i' o.f'BiremllileJrnlin Oermzmy. Wdhsudl kuowi,cdgc: •. ilicci, p:redi.cted Ml<'li~ iUl, eclipseweuld occur on ]::1 [lecmilbet 16,1 O--n,!1i11t.em 'Ine hIDiiII.ey. "'lI1:at ~m$lfless:edXu >Gl.laJlgqrnj~· R~,chtelfs1l.}''N. : A&r X 111 1lndR~,oci·ssuccessers c(lfJiectly predic·le,d1,m ec]ip;sein ]62:9. t~:e e,w~pe~'Qr

mcmunental
wi~h
;:a:

c(Dlltribil!tit)~ was to team up

to tr~llishu:c p:fl!r~of

aJppoo~lc(I Xu a511~de:roft!w'c;;doochff(Jro~

lIesl!.:I!it seholar

Ell!c:l~d:9Ef.rtl"l€iUS,introdudllg brut~ M~!lg D>ynasty iIl~:Q[~CClt~als t~ li1CW mal~h.(:!u!ltic!ll

cOIii!(,';(q,tS-(Hld
aehie VClfIliumt (;; •

~:'Ilhk:h he cmba!rk¢lI on lvit.l'IlIlhIc a~~s.tail!ilce of ~~ilj;its ..Tile ~:ID~ll\v;@_sc(Jmpl((ltdi <lt1i(c'T Xut

Weg~e:m~~m()l~~htFor h~~
to

(k~~l in ]63J..111{lrea!!l~ of da!mused ~oJi~~1try

the n:~vis]()n ~Ol.ln~~d to the first sc~c'liliti:fic c(}]laborat~[Qi[l be>\:'!.'>'eOllsciCiI'lHsUl ~'l EIU'm'I~e: !Uiir:! ihe Hl!rli.a,s!:.

Leon~o
Who

he: hgJis:!D,e COlDl' are d en d!::IJVm.ci ~nd lFr,aI,ds BooQ:'M),

WaJS,Chin!l.'sRc;maJb"s,81nce

:m:!liu'?

Go to the head ofthe class if YOlJIguf;::;;sed X~ GuaJng,qi, last lilllQIlt!],l. :scl!endslSiJl."oW;l ,81 'ii'ar i:ety di9::;i;pUues met ~en;: a~~n~ .Prurb.lt::r ,In:ii!l:itlll:e for GOIn,~~l]l:ii,tioml[ i:o]D~"Y (P~.C.B~~o oOJJnlllDJe:J:l,1.~ B Onlte the,400lh allnivmary oftbeplIblioaliioll :; of the first :s~x¥o[mnes: of l:J{{ll!eli/s ]n ellai~

Xu's
2: I) - _iT:llute

to:mb is a

or

dr~"'efrom

:PICI3. joiuUy :mal !by ~hc iChille{;Ci A.carn:::rny o:fSc~~

CIliCeii

(CAS)

aillii

the Mal{

~ nese <I]iI,dto explore

.0;:

Xu's l'"e;biJi1I1ili"kabie I,egacy.

I
'" ~

I~

.~

;~

'i ~
:r:!i
:::I .Z

.§:

:~ .~ e .~

:;
'!1!

"lie sfm1ed Ch~ll<I's:::mLl~~tIe1l1il1Le;11I11:."&1IY:S cell b:iolq£:I!'flPei. Galllg,president: ott:ongjiUlmi·· vef:i:ily in Shangoo:i,. ~~J(uJPmliUlotedJ d~eid~~of' ' ~e~m~!'ig·1io:u.ihe West" Ov~r thlC past ce~!t wiiiy, Ch~nes.>e~cOOlem have t<'iken Xus advice to, l~!(.':'l!'!JilliC:~u.ditlga r'Cf()reflCe byP:rc8;id)om H~.J lntao at 1,1!s1!n01nth IS Co~rm~~i.~:t .Part)' 's I.7th N~Mtonal ('O(f1Igress te tifuleimIOOlr:l~Il(:'e of ~ . taking a <'~r:;ie!ltifro vn\e;w Qfdcvcl.QPcmr;;li1Ii't.'" Xu (1"1 rmnOUiIlced ~ike "~ue~') was bom~ll ... ~' Sh$ng~1;$i~n.5 62 sml~ft!>.gmcnned [0 be 3 ~ civil Sicrva:llit A w=wtershed mOM{,':n,t ca~'e ~Il 1.6:(10,'when Xu met M!lIU:eo R.ioc~. an Itallan J'l:l"Stl:ut3!udone o.flhe: first Weslerm':l:s anO!i'.~ed to live in Chtll<ll. No i,nteUectual SJOUdl hlJil;1.~· self, .Ricd bad been a.student of Enrepe's ~e.:'1<i:ingm3jhflm ...Jiici,nlilofihel:in,lme. COOSID[1h::r

1l!~;!Idii~!l! Iti'rJh,~•. AIfIl~1iI9 Im1'lilfy :::(IIl~~IIbUllions to Clilirnii. XIIIGIJiHIJ!!lq~ I'l~lped dlsselill~ilateW.esle~11'I ~naIlf1eeg,e or ge,ome'uy; HUe 'jl,age (!if IEtlr:lirol's c~mp~~~!ll E~,t!mlJn1'i.

CQrlwoi!m C,Ii18:ijic~i~H'o tin. b

Phmc:k Sodety. "That's OOwwe ]e1Iruled iLboulOl.lS gl!!l¥," ~ys Dress, a cornputati anal bi,o[og;i I>t wi th <1.0 ab~d;iJ!ilg i.nte-FE::St ]11 science ~li:::l't:oty.."Sudiool:llyilt d!iJi~d ~tl.: e" til'!!.at 2007i~ the iift!n~m "re:i1it:rry ,ofChilloose ElcmieHls. A:CCgrd~,g[y; D!'e8~ brol'!d~ood

Aft(;:f

(l,1!rfli.~!g ~ jfmJ.fll

the 'i,"'11!r:ks,!m.opin~o·~lta. lnrer1]1IUon(l:~ XI,] Ch,Mlngqi Con:feren~~. oo:gal1ii.7:OO.by CAS. the S:oo~~l~i lnmtnu.es for Bi:r;l]o'gimll Sc~e:llil::eSi. !UiI.dI Sh1,!lngh:llJi

CI.1W1;US. "X!Uw<ls''i\fl'no~eherujedlly <litlta.cted to, ] 1.1Ilng~rnmn Cha, ctI histm,',uan a,t the <c Ch[neseUni,ve:rsi~ ot-' .I-~ong:Km;lg. Theki~m.~ I.,
I~

.1 hi~llll;' says

:ii dred sIIi~~ came ~:orea:liz.e t'1~;fLt: pkm<llf £;elil1i1.1.~ l~ e-trya[1d~1iIDer higher Ma'l:};eJIllattic;'l] ClOltc:~l8
~ rhea uIl!~mo'lIjfn Chin a were essentbd to in fi: ""I progres:s.'~1S1&I,i€flIJti~ ba8ic<l:~lya oook<iibQu~ '0 i~ Western lo.g~c;! SIlii)'ii: Yu Slln~e ,of BeU~ng '!!!j A.dimi!1i!;·ooril:m nn~~:rutc. ,0 'IJ ru!'l!Ift:tF!~liliti!lg .E.lefl'letll'S,. Xu :aoo. IRicei<ll~o :£ e coined ·11. ho~t ~f tcmls,ifiehI.d~,gji}hl' aJ(l< fhi2

d:etJ)l"C!e:,lile eq!,l~'Wal\;;!lt 01" a fifl"[),, :h~.the lP~r~acc: ~X.!i!~ni~:a!tiOI1f I 6:04. :X:~was aJ:lm~n~d to o BC:ij~ll.g·5 pres:~igklUs HanlililJ Amu:l~tny;~-Ie uoelldledslumuhly throlitgh 11~:e gl:l,Vl![1ljjmewt m:l'lks, 1)JtnliUl ~~u:ein hi~ CS!~:lee;r liite eameto be knO\Y:l1I" s~mply. ~s"The Miniisterr."'fluoughcmlllli.s lite, ene COlllilUmt\w:s ..i:tis dedknHofl [0 :illl~.p:OOV <Igriaulw:re. His e'x;pe,'limentsilll ill.g S~~ru:l:ghai. wiol :rBlllS,. ~];\Ien ,a new :il1l~:llorllti'O. SC!'1.1f~] AaneriJca, ~edlnt~,n! wi.dCsp:remi. arlo;p~ t:~OIl of the ]iIIig]i]l~e-:I1IeTgy 'CJ)Op. "This wm; dI!eCEldes:be:ml!e fue' 'Vik,st: OOga,]'I1 tald.ng a seiendfic ll~\pmach t'otlgri:cl,d~!IJ.~'\i:':· SRfYS:P~C.B· d:irectorAno;re,ls Dress, Xu a:lso trtLilledimpe-

XI1~~t~i Distrlct

('lOV('il"IJ1M'e1~1:.

OJ~e.aspClct It)fXu:~ mna:rk!llbk liFcHl~U ~he Chinese Ml~erm]lel1~: :rl!ire~ylalks ~bo'l.l!t ~s iris cl[)lllJ.ersion to .Roman Callhol.idsm and b~ptism in 16m as Paal Xu GlIaI:I~qi. All:tnough

sebelsrs ,!IAgM:e 'i:l1lll.t )Gll.(ml1\lef~edOUiI:of b'Tillt£mrl:e 01: :iJJl,recompe[l~>e fo.r .R:k:..:i"s help. Chu snd ot.hers <lire ·cQlliv~n~eddl<lil he was boiill.l,EIdie'llUm IC~uisl:iain and <1IItli ithth~ eOil]ifll~ d;i1:MI, noti~l~ that XIIJ,\'s writiI1ig~ ,cOJm,sis~eJm,tly
:SOD.e

~dl.leretOIC()nfi:I.C~i1m,p]u,j losoph!y. NorV'lre~'Uthe

<I s

rial !iloM:iets,to

:g c]m~r~cte:rfor·'g~~:nnetJiy.'u Ri{'lC! de8e;rvcs

@ CQntrib~Iil.Qll 'of ll1'l1ylbrei~cri:o' (:ldl1cse >cuI.,· ,'" :a: Wre tll1id c;iviliz,at~ol~:' K.ml,owledg.c t~o\ved :f:!j both W,8iYS: Riic:c,i f11:so trnnsklited sevenl
'",

ia

cqjt!£.ll bi II:i!'lg.Yb

,!i!~~~S:

"Hill '!;~'Ushcg~rest t

Jesuif,S as zealeus in their mi,g;sioliih<1lfy\\iO:rk: groll:ps. tl:llllit 'Clime ]01te[: AfltcJfall, notes ~{)!lymi!'li:l'!,.'II'ho Sl)'r~.ad bis intc:re:sts f<.l!ral:'ld R~li:ll1ieir.Ri cd hel[ped tRnslllre £/~mI.m's'\'Vi:defof~ s~cifk;pulfpOlSe: ~taOO;r;::r.i~:l.'says not[!w Biiltlle"-inooc:htn~. OagrrH!¥' Schiifer rJif ta~J(l Ma,'( P]arrd:. Jnstill!t'C Xw:'slegacyWcagimr,le:ril~eJ by the 1(.;0]fQrtlK'iI~]istory ofSd~!ce m iBCl'I~1\Gen:ma;ny. I~p~e o.fthe MiJrng Dynil&tyil!li! 1644.!lllit Id~ X1!U. a.I:oo!!kc.-yI:lgure ~!lChimi)j e:alet:i- gc:mimll coonibu'~,o!l::; are cih~jjisl'!C!d by lmCIod.~~ r.bf rlel)~rm. Chilla.\ {~a~klld~rwa_:s b~fi~dOlm! (l'r! Chiina. "HI~ for~ed ~ d]@,logjuC 'ben.vee:1'I
use

11. J1l~\'frul~!Jecl d,e.'\~ce fWJiIIJiL

was af:UscinatiJiilg

Ernro;pe. the catnuoiiil."He

Qb~erv~d ~no~ions!\lf 'the s1Jrlflnd mO'O~i,. whereal'i tbe West's W(!S baged on av,erage
lfII10U,OIlS,

OlJC

We&'! f.!J1!dChiml~" say(i: Li Ti<i!Jflgt1Jng ,onh~

L!I.fe

"The Jesuits hi!cdbe!ltcr daM: thali'!il Mil1lg astroncnners allil.dill c.lear geometry

S,1Ja,~ughai. ACaJdc.y of g,ocial ;Sc!.Iellces" ~ di.8i~ij'g;~e ~jU[tgl:o.V'.s r~dmer, a:mud more releV,a1lnJt, by t~ day. ~1(IiIlAIRDI S,1IONI!:

733

Who Owns Glycobiology?

A 'I mill P IDf bii:'1~o!lli's.ts 'Who ala iiiliJ1o :be ellle:ltllliiillil~gu!p~h e'ilF~ilEdda Fe batt~.i HI ,I Texas C;ORilllpan, .h:at mak,es t g II'rC!lllIlliIllft.r~e tilile CIllIIiD ani', Uuealtellilii liI;gleg illia!clillil lilts; P sa ys~h e'se~ slcl'e ntl sts a~e:s Ilte'ildiln!!ll fa Ise h;m ds 0
t

Mos,r B;A~HCI~OUNiIISlS P'ROBAB~V dQiIll~tg~ve mnch tllLoug!1m~~o gilH1C:l1g~ 1iD.,crblll teas, !t1lThdhe ()lhcr d;ic'l'~'1 sl~p~k,:mcnnaha,t. t fill!Th.,c~hd V{:~ of ~leSl]h-fou d store s.Bu t t O1rn:c g'f!"(ll~p hss been C:SIu;ghit !,lIPin iSJllescalatleng 'CO~l'l:mversy (liver :;lup;pl:enU:llts inrecens wec:ks., 'llHtil1gthenil! aga:~n:(it Ii n1!llraccU!ticals campiln)" t1lcSilhBlS:been cluugedwith mega.1 sales pr.H:t~c¢s in T!;:X3S". Seve:r<ll pmlil,l,in,ent U.S. g~.yco,b.i:ol:og~s:t:s allege that 'l:i1Ieco.~ palliY; M<IllUmiec.h. t~lJ:"C'.tIte]l::Sto' "til:iJm,t" their

artothar twist, after M~~mu~t~c:~~n~1 uthen OOl.'!liPl.ai!~IJ;;d about th~ G,y.cQbior'og}1 edltorial.lhep~lbli;:liher,. Odord Unhl'(::rs;ity Press. re:~ovcd it 3 "veei(:s ~~ pr'OIl1]sing!o relP0S:~
jtl:aJtCli 'l;!i,lHh ~iPO!lS()!5.

Gl)"Cobi'oJogy 1!JJ1IJ lead <I!1.dhor ,ohhew~thdH:!'!.¥nCldit'orJ~.Adds.AJit V~_mki,aglJc'Olbio~O,giiilt a:t the UllJiv·ersh:y (lfC;lHj1:irn~.~. San
DiegOt~l]iS "st:rIking

MSiu:)'niS!tech Jne., a p1ib~]~ly trSided 'C()If,IiI:$400 1l1U]]On i:11JJ saleslasa ye,nr~ '\V!lS um:i,er fi.r,[!, ftom legal S!!:It~u:lIrurue:::: he:lim:,e thi:(i CO!llitrol!,l\e~.~yb:iok!e. In ~l1ly. he aJUorueyge[ler,d t Qfl'ex~s dua:rged. 1::!()H111)3.ny with vi o,l<ilii~ llmgTexlIs laws <I!lId has s:m:dl~o slop it:s sales associates from mllkrnng c]liIhns l:hat its p:rodJ[~cts eure di:Sic:'ases., T~llie 'CO~ll:pany bn denied. the charges but bM s:1lilld dHJ,tit: is ~tvi,s,i:.~ts ru~teTllmlie.. :~l1ide,pclld:entty, !'lC\l'er~] u. s. g;iycoblioli(l~ gis1lS sfly91eY\l,1'$nt to Set~le reeetd ~1r,il'ug1i1lt and p;rovel1t d)<,ullag.e 10tliiLernr H:c]d."ffsliI;onc: of 01!U' bus~rI,es:\l as Slycobio':log]us~f Wiij)'traeeiWlicilJ oompa:f.ii,e~wa!tU to sel ~b~fk c;Xitr"(:~, 'Whef! ~h(:y~i~~o tic; it 00 Olllf dY8p!tny

in COIP$leU, ~exa:s.

w;~th

III 0

re thalm'

field by liJmlk9:ng~]ycoMo:~ogy discoveries vii th e laiias :for :sugar llill'Us 0 f flllfH'l(fV e 11 III edi cal ben 01]1.. Tliu: C empa ny and :i rs
C()iI1IMI.~t1liH.h" w<lve fired! back, urging the witl~d!raw~I.of ~ crit ical conan em~[y ,at! d wOiIitni:ngofleglli actioll, .. T'e dispute began whcIiJJ 111 eaderi 1[!J! the Held :and~l!;;~ditor of'd~ j:o'l.!.l1'!:al.OI),rommo'l1)'
j

me

exar:!l:ple"u'n~i>I'.r.%tc:~ "the ~pOOtnil!i~biHty of f,Cic!l~lst(1; ~sp(,'3k oot" u But otlherSt i~l.dud:D~.g seve:rra11E1!I:rQp,ca:11 glyc obio']og.i.1iJts. sugge:!!lttha.t ~hes e c:rHucisms $In~o''II'Cr.re:;u:\hing. The ·c:l1Ji:Elf o:ll!)Elnizer ofth:e Br~b]:~n eonference, .lokn Axford-;Si BI.i.rns:iru rheu1ili'lilJt'O.~ogii$tr <Ilnd until recently <I .Mannatech beard ull:::m'be.r-SllYs he, and. other orga,]lJllze;!'s 'livem "fl;Bibbe:rg~Sled.'" by tbelettelF sugge..sti.ng 'speil:k:eI:S, not arUt'::litdthe
conferelU:~. He says M.lI~inl!lItelCh'S, S!U11'J!port is

no difli:~ren[t1tol:u the dlll!lJi;company

tliuOlt funds

Mmley

cauntless sc]eIllti.frnc, ~lf1:ee-rings. H~s: cemp argues, t~l<1!tt~.le lllUil:lllt:echcritics .M.•

OO--3i!ijlho;red.a ~ea!lbi"gcritiq,ue ·of Mamuuceh tviwieb WHSp~~N.ldali, an oil~ii'leprepft~l't iii SCiP~~b:::r. O~.hC!~icnti~8 jigi:)'ncd in" ~!ying
speak!;)rs~o recQliii5,id\:;rtlinefrl:p~rlifuipa.'U!)llilla

~1)(lILnlfllI.irlydh"l!!Im.iss~fi~, ,ell~in~co~:pl.ctl~e mental)' IIiIIIled:i cine in dl!lstty. 'l:l;'h~t!mJ should I!:I: :::i, be ~lJIc(nlira,g'edtQ take 'P,lIrtilil,$cie:!lrntific ~

m(Scti:n:~"

!'i0!~ba'iWti!~d&o_

the;m,

~:
Ii:

~de!1lt!fic: meel~.ngl:aJs;!:weeki nDubl i~lh(lJ \"~(i, pa.1r~ly spons,o,red byM~flll1iat:ec~. [11

cipHne:. thi1iiti8 th~probl~lWii,,'~sfl),I'lR(!mild SC]1JTII~awo.f JQ.hn~ .H:opk~!l~ llni.\'e;!:'Si.'l.y :i~ Ba'~~tmo re, M.~l:y land, edi1Q1r- in-ell lef '0 f

~S l!Iglar ther"i:!Ip'~ ~~ "'I, The scie:l1l(;'e at the heart ofthis d~spute ~: C"H'l'C'C rns not d i.etaJr y slUJg.f!r ~ but :5l!gar 5

::e:.

734

NEWSF'OCUS
~ Sweet tn!ii!/mJi'l!llIit. M'ImI1l:Btedl'S, n<l!;j)hiJI prodlil;CiI,. ".. A,ffIlb~oto:'le{®rnp!~e~. is a Mud 001' plant ex.uacn

to;:';;lll'wm ];IJe1p..Jr~mr::::-oPal~~,wnof!h~ :Scri]JP~ broa:~'t 'CfJ,l1!CCfam'lcei,ebilia~p.aLs,y t!looicd\i-~,]th Resca:rchl!iUsritutc it! 'SaJ!l .Dic~o" Calif()mi~j gl}fCJCDn.1!,I'm,clu1.il ~1:50a~peair'oo, in the Pl'()(;..ypra/:. M.1I!nlHHC clil. starred ~y ent:l"Cp re 11 cur beg1)liIIg,c!l:li1lilg Cfll~!~l'i,~ncr be became Il!tcOldof :Safllj,i!l!d('~st~r, whu) 'h,~dprcv[(lu8-ly run a gly'cabiology ()O]!ll~,ortium funded by ~:lrnle tng.!l O,ftJ1(J Ftshftl' lu,~mrU'(!.fQJ' MedicaJ ni};S.~'UJ'tlJ.w~ic~~ ispultlli~hcd! by 1)n ~ld!I:'p('l11.d'· N~l~~ltniS!llnsrimt~s,ofHe~dth fN1U) i!!1200]. b~s'i~(,';s~C5,:licUilmgpcst-COJ1Jtro! de'Vice~ and "ru~.j!,Ist t,~.J[e.eup klID{lwililg Jfly u~me was ~omeliJiil~~I~tion.I~I,:IIlChed its first product 'eJm~~ni:Z~llioll descr.nitlcd b)lthe 'ft.Q~Attar,. i~ ]994. T~S!t:r~r" CongJ'L;lS(; pfl!s~cda hlW neyGeil~mal IDi "~in.l!eW(lI'e d1W!n,':l!>~rn;rnnchSl~~ty being usedin that way," ~,e :says" Tiruree ~UO\ving cO'.mp!lllii,i.cs: ~iO Ken die~~I:)'$wp:p[e .., wi~lillh()o~e: ptu-pooe ()f:p~\li.dilJmJg 'SCi(:11Nf"~e· Nobcl~rize s '\!!'lImer!ii. :ail R'ockcfel!er U~1h',er.CU,ts 'W.id~,C1rutFClodiand lD.n.l!g:Ad~.ui~,'i:i!tJ.'a~ Sliilpparl: to the ml'egal health cbims:lllade aJ!tiout s LtiJl- inc hid i.ng (li flute r BI cbel=- fH ed a t:iOllDl",ppn:i'!,f<iJ~,<l!; long as they d01il, '~: ela il.ll c;Q.mp~.a.]n,l~ ~n MilInlla,~i;:chI3styeal!: to aga Sit Ma~maibech's j?!rOducts:· afny ther<l.peuth:: bem'lfit. The: COm:PDIlY~S Asfer p,eeF~r-ev iewed re search 011 the Ill<llre the ,co'mp<l:llYand esseeiates stop l~s:inri!J!: Web sije stEl~e:;;thatits g1ycQmn:t:l".ielllp.I.'od~ health beJmler..~lli of" Amboo~ose i:nPllbM:e;cl]~ iuhdr.m!Llne:s en Vile!) sUe:s. The O(m:lllanrDY "has listed jo:u:nl:lIls, there's net mach, <licco[d~ng accepted $mnc 11e-sPOr:JISillhi.li,ty"o p~tmi] sueh t ucts "'lIPP~Y concepts fi~on1l Uille :rap]dJy emerging fi,dd ofg~ycoblO['Ogy:' Apl1eSls to Sdlill<ill.f and Freeze. Their revlew efthe We:b sites. s<liy:sR.!Clc~e,t'dlel' Cl1iI,er-•.tI cDlulisel. g 1;I~rriet .Rabb .. release gees an 10 say thiUei~hl s:wtgtms"~JiI1e l,iJc.f<IJtwtrein the past &5 years found that larch b.1liIk :[II.~[lb]nog'<IbctHin ~:iiIJi't dli,g,es~e~d, h rticnJiI:H1r1yd:i:s~mili.i.~,l~, S£ly Sc.hn<l,[lt !lJlil,dI WJc'ede:d<llt the: cellular level for optimem im.lIilil.mef~nct[,on" b1:1t t~,l t "si x of these a lInd ~u, main effect :isflil,tu~.el!lce'. AMut )10 i1:1 I'n:,e:;r.e. !lTe~cfer\lnC!es to me 1J001efi~sof glydieta:ry gly:cQ:liIlmrients ."' <lire,o.flC]1I l;Eld:in:!1l co:rmUierlil~ in a .cd~·cll,~ ~ext~[l'C)k called vltre and anim<il~. tudielSOrl!ili!i.geslili!Il~: 8 iall. mill modern d[e~tfl.. The c(nnpiO'l!ny:!J~naJ~n 1JJ[,Q(:ge'l ;11!II;colmannllliill,l.orurs;e]y tb.luilied by fla'l:lJI!I"S litust.m'ell i3iocitemis:lI,1 from ' prodtu::t. Ambrot'05'e OOn1p'~c"",-a mi:1(tnl!e Malli'lO'l!t~ch oMits S~If:J:plier cjomp~ny, sug;:est McG!C'II'i'V'alrfj]~"vhOise 1~<Jcl ed!i~ol'i~a Ilet:ired sysh:i!ti cffij1ctl'l,. but the()!il1y Univc:rnHy ()ifThf,ont'O bi,oel~e!Tdsl"!'yp'~ofe:sofl~reh bilflk Hrabiiiop[iicliiWti. aloe ver,iig'C~" ~om(i ~~nfll!!Uiti·e gUli!Ill ghani. and SUMU'ii,g:aC'i~iiltb-i~ "a elm leal ~ri,i!!~ ·~.PubM ed- [i8t:~d J01lD:fn!J1 in ~or,.Roben MWflfaY, MUWfo/" \W~ino alse a iii! bl,i;;nd~f spc(:~fil(; pJilI!1t s!t(.':cl]ta!ri:deiS U~:1!it ::mp· round ~.Q benefit, Th~ !lotion lha,t <litiy sacMa]lJoo'IDQcl@ CQi!"!~l!idl!lill!'~,!Kl!dcd pH!tdg;r~ph '~() a por~ the hnm~!1e~)"ste:J¥il" gjj!'Jd"s!:!PP,,)ft ~pt:i- dHli!i.de m iKt1!ilfC W in ~!l1preve h ealth hi t he2f,H)6 ~d!hi.Q~ fl'll"iln,g that ~hhoug'h t~c ~~1"!] cell-to-cell !cOImra.ffilJ!:'!:icflltioJilI,'" :t'I ProdJiiCit na,w~d. says Vark~t boca1!JtsernQs:1 p,e~'ple'l'l, body oan :mak!e (lI1i!lIer mOllosacc~arides fT(l(m d~tashec't ~8a.:y(;. !cells ca:unmake;(1!U the 8ugaJr.slhey need 'f!:l)111 gl1WcG\se~"'l'heliC is evidccO!ce tih~t '~e otl~r s;~gMa!tm:I!l!f1te>eh relies 011 mere tha1lil 5-00.000 gllh:::i()Re~n 'the dkt aIS maybebeliiid:loial. ill ~ome ci~rClJms:mnCies; hl~epe:fldeliilt salespeople; or ~ss oci.~tesj.tl) Degpitel:he :S(:$~lit::l!l,IiPport for g.iycoifrn!l1ltl:i~ wheu ~ddcd to the diet T11i:s~UI sled ttl the !l:eIJ A*br,oMse. ACCQirding to a I,~w:~itfiled ,enlt~ ~n.nlal.m:;:'lrem;u. s c:ienrn f1cp:u.lbl. i{laHons,~ devek}p:IlI,1!e~1It of g!y~onuJ:ri.ellt: :S1lJ~~,pi,emenIE." wb:ich ue"u:I<der iit'tl:d.y;" '1:\';1;(':. ~e:l{t iJiilJuly' 200'7 by theTex1ts Alt;ton!~ Oe ne r,f11, the company's ~ s::Iles no~e s:, :Sclms9.:rand Fre·eze SIIY <Ii sso ai;EJj"~es pl1ornote i.~:sro d;u:cts: p this sr<l!temrl!ellt. which .M.3:I]Jna:tecl:i witlliii, tesHmrN;dal:s frollDI1'p'eop].e, ,cHe;s in a faicl s;hee~. could Jmrli.swho c:lai.:lilThg~,ycQnrutrieJ]Jts ]~,<Ilye, h:ad )lQ{U:lg Slc~e:IJIJtis:ts.,tblldl dDdorn. cll.ue,d! dis'eOl,ses. such a.s Down M.uRay ~-'Spo,ru:ls tlilCIt: '·'tlu;;hre :~s :syu,cl'ro:me .md cm.l~er.. TU.u,~cO:llll~ SOJlilI1:ede:l1IItlfic b"s]~ to the way S lpilluYtdso "~,claims: sd,eJ~.tif:ic va.l i,~ [Ambl.·otoS'e] ,t1ffectswd.lness." cliation from tbe fieM ofg;]yconQt~IlS tl:m,t ·'thouslilnd:s of people ""cl,ence"fo]" ~u pn)du.ct~. the .c hdm to have bcnefiled'" from AUome:y Gen.e:r<JJl,coudnded. it He: S.~y8 :1M31:1 .... 8 dQne['!ot~l~
M~liIrl1J,WClmiS<li!d ~nl-e"sPQlrl!Se thal

widely stilld:iedfo[ their roles ~n normal bi()':logy,~nd. d~5e·11~e (Sci(Jr~c,c, :2:3-M,ll!lch 200 I. ~. 2337)1 .•

['E1~i:fbrll1i:ru.examine MalrUl!l.tecbi's edllCa,tiofl!l] Website, Glyco;Sde:l'tce.org. shUltel.'ed Sllrloe, (.!:)!lIt~iI1l1mJgl p(J~ysa«(h~lI1di~, AIIJ;gtus,l:ro:r revisiens relatedtothe .AitOfIil,e'y Ge1liend suit, Mm.ln<l!lech !>lIY;S, he. ar-ch]ves T :m,ph~c1lllIe's hnked tcmcsrpteteins ;8111(1 inclnde a se~f~.e.scl~bed "peeJi""'!re,vue\l!i'ed seiea.a!llymtsiIl the body. These .w~yt:joprote;i~11 s ~JICj.oufiI.l<ilJ."called .riiyc()Jrcie.IUJ(! &: Nllf.rin.cJIJ, and glycolipi.ds dlotlthe ~1![rf3,ce: of'cells and ,edi~(.Id !by M01l!lniltec:h scientist~alliclco]ii'8lJ:QUs~mve as id eJiilti,·f~c;Eliti,onliilI11~rkeli'Sl\eCO,W1iimd anrs. Its articles desceibe g~yc;obio.~ogy by other cells, l1u:: field look offinthcp<lst fi I"idi.~ "ruixed \,1!1~tih speeulati,ol'i O1Ibo !!llt the :2 decades, jj1J'!Id~rbol@ydrUes ~re now c pote ntial of g I:ycQlTi~:tl!~ents to p'" 5~t~vely
t

lllilJi1JJYgl.yc(.bi.ologisl:s have fbn.md their IlaJmes on Web shes pmmO'triJJ1JJgM.~m~ruteeh products .. Re:~e:renoes to Freeze's pil(pers ll]JPEt<llI oa.l. Mamrn'lIitec:JI S~le~s beeause ~2 yeaH <11.0. he s:l1l,oM/edt~,l;8Jt i~,~, ()li~il.dr-en with srare St]g1lJ"'pJfOcie!)!sing di,sellse Ji'ecO'II'ered if th~y well'(lfool maanese, Ever s~~loe. Freeze s.aylS he hastre!ceived eta,lIs <lind e-mails i:h:nn~~m~]ic's afpati.cllts wi.th diseases s~ch mi1cailcer and ~1,~ti,SM,. They want to ll;tl!",,,'if:spil;ndi~,g

imp~ct" vmouJ'] disorders, "¥fite Sch~~~r ~fld frcei';e. Cia,8C; report::ion di~Je'Hle~ :such as

$34. :$:I.OQ'.,

0:1 ~~or~p~r month

em Ambrc-

it "il1lH,Hltk~df~dJ to' OOOpCfaite: Hi' ~ re~lcll a"eso~utOC!:rrw~th the s,Mte:: ; ge.~!1.whHe,. th(l; Attor~ey Gen·, § cr~]1g oftiCi;i ~$-J'sth~t it i~;i.iI!,~,~. '
f:,l

3:wd h11!,; diClTl11f!1.dcd thl!ough a I:av.:'yer that hi~ Jlmnc; be

i.f!I.gliWO'llg

f~li!novc:dt'rom the (ld~tQrial b'y Se~lli!!i!!lIr~ticl :Fr~eJ!:e.

~i,~g. the ch1irgefil i!1l ooun. ~ Inth-eiir CQm!'!l~!1Uwy~Scl~:!'iI!m~r ; ~nd 'e0 -,~uthQr H ud.sQ1'!Ifree~e ~ of UliJIi: .~ Uf~llliImJm h~sti~ut,e for IN'utr~(I~ulic,a[ls; 1iI1@IB!']fWe,j'g hl~.~alilni:!t~c:Iil,hu:", hiiNldQ ~ Medi.cal..!i.eseamh til San n~ ego, :J:reiltas, ad !\ales last Yllar o.f!lllorelhi:!1i1 S4i(Jl':)mi~~,ioo, h

The ]e:!i!:n!e!J' m:e:eti1ngl The ~108t re,c~~,~ ,exa~pi~ of M<lim~a'!;eeh":ii t1i1.·c~'ic.s" c:ritlcil ~f!yj' i<\l hS(iPQ~$!;H·sb~.p ofthe ~clil!'!!er lUiairt.cr~dil1ll((l!IP~Cl~. (Uy'cob[,oIogy aluJ Mc:did1lille

NEWSfOCUS
Symposium a bienlli8i~ 1IiI~!ootillg OIgani:zed by the [Royal. Society ofM~dici:ne {iRS I., a u..K, eduearienal o:r,ga.l!'Iliza.t1!oIL xford. a member A urlhe RSM board and. head. of a research cent:er!!!l: St. George's Uliil!i.ve'r:!i~ty' oflol.'idon. tliI.e
~8iS

,m'ga:liI1i.zed the: meeting

since ~tbegJ,I.1II1 in

~'991 ..Axford served on Ma,mrnEIItech S bOllrd fiJ.'OIml1. 2002 I1m'ti I he sret)jp'ed dQ1i~ll ~D1 Septcrnbel~ lu: 11m!; eceived at least $420 000, in com .. r pensatieu, $370,000 in stock and S2 1Xl'.,OOOin research contracts, from Mrllrnillimtedil since 2000. accordi,ns toreports med with the
1

posrod

U.S. Set:;mities and ,Exch,mge Comntissiol.1. After Iloe 2004 J~['ifi.el! m.ecting, Mallililtech
OJro,

its OIy,c(JiSdClm.cc.org sltea

Dlc:g[o some g:lycobiolog:ist. [objected .•

Aceording to Scripps 's P~ul,:il,oll1 he ,!lnd
othel.·loce] organ:ii:ren; asked RSM rereturn $3'0,000 i.n.:I'lllpportiTrol1l Mannaeech and aJf~e1l"bll,~:. the meeting was, canceled f01l" t lack of f[[lld~ng.Axford s;arys the I:lle>etling, .arpe:ril:!ec<luse of lolllil' n;g.i:str.<IJtiOlr.Ji aad ,EI t failure to< find locel sponsors, Th~s year, ~he controversy blew !.lIP ,again wben Selmaar and Freeze decided to send the speakers ~nViited toHltc: DuMwll meeting OJ, m~py oftlilleir cfiutuc;a[ editorial, along with ;i, Jetter :siglle:di by themselves Paulsen, Vmrku. and

i!ng th~lt:he m~cting's "':m,ajorsponsor was t Mannatecb, Inc," la:st year when Ax.:fhrd prnpesed Ilo!ding the moeHn; in San

garry by A x fuN wIith an adldedp'hr,f1st: st~l~~

sum-

16~rar)l' Liitemuu!'. Many clinical case I'i2porits ,CllOdr'ev.iews or Ui~ liIiflallh ~h~ct:sof 'I}lyc,r:mlltliients havll! alllP@ar,edi ]11 two journals tlhat. iuefl't lis,tIlt! illl Pl!IbMied.

could post his Sl~mm3;ry ef'the 200~·Jenner

around their R&. [) d~IP<lrtm~lIllt" The Texas

fe,n,

The other four ur,opl':'aa'lglyeobi.o~ogillim The' editQriial'MIillni.shes who Clo-orgi!ni~cd the JCililerm~ctiilg agree Meanwhile. Oxfo'rd Uni:ycn;ity Press :il!ar:.l, with A<ii.fQli'd'~view that dietary supple.hdm Hopkin's Gerald ~I,;jrt.lJie l~ttera~]e;ge.s removed the S.chnaiiiir~-:fe,ez:e commentary meres ere widdy u !led and should be ~tll:d1h[lt M.mna1iech sites have "pmmine1iill,y dis!" andplan~to p~:.;t ~tl.ateTw:i~, r,e~pOlmiSe8+ 8io·, fed. "This tndu!ij,t:r:yneeds 1:(1 be iucl'i,l:d.e~!in pl,~" the: Je!il~~rMooliing end tbrrt"yo-uJr f"l~~' s!Ci~~(;:[e til sen i"or ed ito:r CI alre S,i:rd S>ai)' I), sde.ntific m,eetilmlgs~'" they wro,re ~Ila l!eU:e'l"1lo .oxford Pr.ess bd received [C(niliIlJI~.a.i.11iI[h; fr.om ticipflltio'lnimay be; misused to ~nq>rel'is, mis'lea4, Sc:hmlRlI'. Raymond Dwek ofOx:fm-d. UUmi'\IIElf= or [coJ'tthlS'e clleNpernt,e and vll'lnecaJble :people,:" slty. who eelned fliLe term "'glycdbio:logy" in Mannatc>ch,. A:cdbrd. and Murray 'that the ari!!ldc was net prop· [t lH',g'l;S spc;:lIl:.ern to 1988. concurs" noting that with US. health= er~y peer-reviewed .. food SllOPiS "fun of remedies ,md ekil~esc ma~' sure the moorklg "It's none of our husmass The authors arid the medicine," Icml1ph.'!menlary medicine can't L not sponf;l)red by as glycobiologists if press have' agreed the Mannatech and take be: ignored, NIH has reaehed the same "wha'lcvcr actions )Iou nutraceutical companies posdng should be' eonciusion, U,:vek <lind o,tben say. citing a H~V ised, Schnasrsays feel am .3j:C!propriate: receru NIl-,jJ-spoJm!sol'ed stud;y cf'glucossmine want to sell bark extract. he: illJop,eslfo:r ",81 real Theletter 3!'pparfor artlui~:is. When they begiin to tie it forum 'with space for Dw-ek disagrees thil,t :Mllnml,tech':s plr3iC~ ~ntlyh~dlitlile iln~acL tu Dur disclpline, that is Se:\1e:r<II~ spe.1ke!;!l tDld <I. Hi nte re S tedp OJ g,'~ tic es are dtJim,lgwn,g the t'ie:~d he :~el.ped !WI ~ Science dU1'1 R.S,M the preblem," ties,' Bird says ,guest found ..ALtbough he once wrote the comediters will oversee pany ro ask Lt to stop, using the nmne of his ~ assured du:m that -R[]nald Schnsar, the sabrnissions, '" MannatC'cll was preinsnture • " ~t~jnk gJycobiology is bigg,~r." \tiding an unrestricted Johns Hopkins Umv81'siOj In its letter to savs D'I,.fck. "rn don t think it s harmed the Ii! educationalgraatand Oxfo[nj Press, Man,·, field with scientists." that itwould have no influence Oil the content rnteeh calls the ooituria1"a del:ibotatc <liltaok ••• E"en Mann~t[ech's erincs agreethat ~ of'tbe meetii~g.I~SM "set lIP themeeting in ,il based on false s.tallCmcMs,." The company, research o,~ the p[(ncll'l1:t !learnth benef~r~ ef i~1 ~ Ilfe::S:PQnill]bh: and seasible manner," says wl~ich pllwided S..cfeiu::e w~tlh~. cOp!f o~the ret·, C, OI:1.S 1!l:1:11ildU,1.gs;~pee i. fie ~ug ar ~ h as :biiliic:r t. ~ Allt1i:ony O:Jrne:ld of Bristo'l Ulliliv(lr.lil;uty in tl~e rer and a roSPOISC to Gf,yoob'ioJ.DgJl cites :ti'lii!1.n~ Val:'ki. :f~r eXa_pho; s:~~ ~;e b: il'ltlcre;sted in ~ U.K. RSM cduC:ainlJlil diirec,tor 10 :Parkinson 'dlilrl! n.1;'(j d~ei'!l sludies, 'iilildijd~lg IliiJf.i"IJ!k!1I!wd·, si~ru~cacids: as lr.eaitllil'lli=llts 'but feels "'mMb~ WN.'Ua: 50 fence tha't Mo1(jU\wt~h is jiu:u ailC of k'$ :it' :h~s pUbI.nshe-d or p~&elft:ed at m"'G:Ii!lil~s wted" became of the sUgD1l.a llilUlched. [f the ,!t!ld .says it has spent more than $20 mmi.on ~ f~ CQinpany 5p!)Il$Or.i; a!ld thatRSM policy field ofglycobiol.ogy h, to expand, many iii "in JlO ';;''f1Y aUO\vs the Sr,001:sor~!1gcomparl)foo [on rese:a:rc:b.. !Ieaders agme~ Ilea.:hh cl.a.inu. muslt' be based Aido:rd ddends hh; iin'llolvcment wi.th on sohd s,c,i!ellcc. ~ claim ii:iiiry as'l'oc~ation, w~1hthe RSM: Axford ~ t,(),ld ScicriCe that he agre~d thait l\Ihm.11iIIlte~h the com,pB It}' saying be's "he] Iled them tllrIl
:E

meeting an its Web site fOf educatioaal p1!lIr· poses. He says, he had (j'VleiJ]oo:kedi until ;r.lO\I,f ti:lil't M:mmu:ech ha d addeda pb:r,<Isestatin S thatit W1JiS the '''n'iOilj.ot s,onsor."whic;I:i!;WlS ineorrect; ho ,,·IYl!. Pari'kin:.Jon :Sia)'~'the;ro\\i'ilS, :110 viola;uon ,of RSM poHcy.

Attorney

General 's allegatians are "appOiU~ng"if true. he adds, but: they remaJin"uW1prOVertl!.'" Axford stepped down

the indcpeadence (If his research for the company. he gays.

from M iillnaroch '$ board this fa U t'o en nrc

NEWSI'OCUS
NUCLEAR PHYSICS
Oe:l"Hla:n ~ate of'Hesseu The labstarted mut

'lIV~tha. :8] ngle linear £I,coe[eJIil tar tfu:rut ,could

~c(]e[eJF:!Itenn:v element from ]ruydrogcn to arranium up 1:0 20%, of the, speed olf'.liH;ht A. s)llm,c:hroiltOll added later boosted speeds to
90%

GI~rm31I'1iV"S GSII

La,bo1fart,oryllJimsto

11:J,~'cGmll~ eU~',ope'sp,ri~mmelf nucllea!t

d:OIlfS,

lPllily.slcS ((1'11'111&1

'wii~~ al se,t IO€'iiJCCel~elratoIfSDlli1ldldeb!

tlillat win ~'~h'e

€1.2

@ImJVY' (J,ftlilitB waddl

ofli.!:"lht~s.,

DARMSTAIOT, !G!ERMANY~A~~l~.mug~ilitcammt yet ela iru ~ns.t'ill!ni!lme tiec,ogn~ti,on. a Oem1,l]iI natienal ~"Ibin t:1mlissn1a1~ w'wn near

~ill,i)Oll prioe rn\g~ "Wt's <II big,r1ew venbIte, a mylti(]Jis.ci)p~ilil:rn-yt~ldhty with :i.1i very broad iIi1~,lffi,;e ofei'>per,ilfl~,erus." 8iliYS :Sydney

111"1. late 1.990::>" GSl'sre:Se1li[cn,ers: me began d.i.!I(;lIS::liO:Il!:5. with tile I.200 eutside users oil!

its ]:5 millil!te:s O"fhmc se,'\flCnil~imes over. aSI. as t cm:Ued. ha.:ii

rmnk[H'I:
fOliglOd ~C\V
seen

1l.1li5 earned

~hem]C<'II]elements never refore

~e~

G,deti, director ofFnll1~~"s.heiil,l'!,~y.;i:on lehora~O!lY GANllin Caen. Those hW()]'f~din d:eslgnif!l.glhep!'ojr-"(;t <1m ecshliUc,. "SUtlftmg
M!p such a facility is ,f! once ..ln-a-lifetlme chance," ~.~. FAJIR p'h;y:!iicil!tTb~!1~S Bdcr. Witblhe 'wide array o:fhi.g~l-ene'rgy jj~rti.cle bc:lO\1!!~~vail:.lbllC ~tFA,.I ..R, ~re~~~'he~ "vil[ !be ali~ewst1!ndy the p;I'liiticle ~o1!.lp ~~ifLt elds~oo 011'1 the 'Very b egi :~nin,!,!: !Of the univerne. the wo'l:'k:mg.s of ammie .mldd,.the dense ~,;)s!m .in the eorea .0:1' bTOi1IYIl d:w~:rfs;Rndga:!1l=g~a:11i1 :S~iI:fS.hew steUm." expl,os.io:m creme he;avyel~
Dents" and w.i1tetll~r anti]ruydrog:e~ml diJt'ern t'i:mn its nermal fo:r~ll,'hysids1:s here and elsewhere are 3~re~dya:dd:ress~~~;g these q:l.!le~ tiens, but FA.IR:wili. p:[1Qv:ili:ep<l!rti!de beaims

wh~t tilil~l!i!b~.hOtgMdo next By 200 l, th~~!]b h1td dit"dWlTIl~1P acoil!ccptll.UiJ~. dc:si.W1' report tot a f!!(;)W tl!(.;n~th<1lt would e;lflfll!1d Oli! GS~ 's1>l,iQrk W'ithparnjc~.e 1bc~!l1J8 and o:a.ddan aibHity to use ~ntipwto!1s. G(;lnn~u~y's l:Cd:end gO\~rfl'tne:ot
~grned to I'll!l1ild ph-n ]f at ~1~8t 29'''':' of ~h(l the C!l)S~S~!."ebOrlle bY' f'Orcign partaers, So· '~r •. .~,3.p_1ntuers ~p~rI: f1Pnl 6e:U'1ilI1~11Y have s,igneiCI up ·i~.d~ucliing Gu:rorpeocfIJ nati.onS and .R::n;'~i::i!, h'Ddrua. ocn:d Chin!!. {"rille Udt:ed SnuI::!J is worki:ng. Ol1~.I's 0\\/1} pblll!>lb:rrm:e isotope resf;rnreh i m:idis not involvGldL) Cml$tI.oq,.u:tion ofFAlR w.iU be,gjlffi!~n aJ ),'e<lir" <lid dn~[(I(Ji1ity sholl.!l!ld be complete by .20 1.6. GSlwm il'ieJ,].l.<1~n a German i.ab, EIInd a neFW COI;UfliiHlry ~e~ YiP ulldier Ge[m~,MI lFIW will :mn FA[R but be owned by the ~4 [m"f(l11I!lItiol.l~I. pilttU.Cr:s. Tilfuis armTilJg,e;mmue~n didn't .SP' down weJrnw~th 8()tmecountrses, p01i!rt:icuh.rl.y

00

Eiif~h, Cr;:;Id.1!i'iUe8 tts O'l>'i.1ijjl, h SUCC-~$!llCS

by presontiJrui!!: visitors to t11.ebbw~th;'J :packet of~~x c~~!uli~s, in d~ff(;)r,(J~tcolors. The nrff~

i81:abe]():d"Bo~rilJ."i'!~~d 'ltI(:ar~the df!t~

d:~ (JIl'lwlJik,:b GSr'~ ~~1!I.c'Ie:~f alelm{~!1li~~~c~t~d tilli£; e~.e.emwu,u~ 24 .~ebril,Uljry~9:'U.the ~~om:i~ Imr!iiber H)7. 'fhL'lI~!1i:~I!C(lre~l'Its: elelfau;:nl l. l2. (ij seov ered ~n 1996 but sti II urmamed!li;~t ,~¥ait$ ye~~fk:ation, AIt:ll,ough a. :rivallflb has a,dJdec'l flve IOliiler supe:rhea.'\Iyeh!ments~o the pe.riod~Gklb~e. s~loe t;'heli1, GSi: hepestn soon glIdb tlra.ehead~
.~iim:sRgII~n,in I.mmy allle<l!S,of research,

Over

tJ:mnext cie(];<Ide. the rnaoli,\iill more than doll.li~ ble :i~1,size ..\iith the eonstmction of two hi:g;b~ ellieilikcr:f ~l,I[pciroond:m:iliIil¥ syru::luo[u)ons ClIpllli ble of :a:coe]e(mtiill~'1UilY !Ito:rn IlJj)tO uranium, th~ee :lit IClI ge "]'in.!!j;l toe oJrud,iti en p<airt~c~e bC[tmg"rnldI1IJM'ero~~ new detedOtS .~efvlii'ig fi,ve ·diffuremfDel,dsof physi,c:s, COifasm...cliiOIi1,
a

with as :JfIiltll::l.l asHI.OOOli.me~st~:lC lnttl'nsi'ly and 3'0 t~mcs, the, cmer-gy of those ~.rowdivail= t1ble [l,t thelllib,wirtth the ,added bOIil.m. 'OftI11lti.g~t.ter beartt.ls 'fr!fut'mlCJe l!!J.6'ivt)',es of experiMent'S p ossi bl,e" "Th~s type of mll!Ch~[lc1l1i1,d

f'nnce. whicJiu, predf"er~.'1I.:'d ~n 8o:me eo;untnes

~wte:m<l.t]olllial.

b.OOy li100 ather ,pa1~.-E!W:rope.."Ji11 re8el'lre.~ een'~. AUho~gJl U1l]~ ~S~~ clIkln't pl'~~ 8110,,",'1,!st()ip'P~, have :yeItt~o Qt)nfi:rtI1

ofthe new il,j'!wt:iOlrnfj" dlwbed the Rl,c~:htyfut Antiproton amJ: ~Of!Rescfl!r(Jh (RAIR},wili be oft.~~ci,~~ly la'lJlrM".bcd ~~ext: l7ilc,,-ek.FAUt will be aJl!i.!'!!t~r:!1!!lHorHd aJf1lirmwith .ore 'li:liO'!!'! a
dozen other
COtlt:ll:rie;s

cne:rgyis tlottlvai~OJllJlC:,~iiywhere in the\<\'oild tod!ny,,"'s~,ys G~lle·s,."I'M Ir;lilger to !je~'!,l'~U1t theyfi.m,d:~

Ifb:otii,l; :dgdiie~:

(; S lwas fo unde d iu 1%9 as a sh ared

1iC;S'OtU'CIC for several R,jil1tversitks
hill '~l\III;:

OOriltriJbi~ttimg to the

'l~i]'fi~!I!:'i¢i"-il'eO"ii!itribultio:n. OSl umdfAIR if7l~cnd w,ofk ch;)~cly ~:!P rog,cthe:r,bu~ ,finth~t: ("liSi win ,,'1lysh~a:!]y ptt:lvide;t~the W(;,\/Ii fa(;il"ityis..a ~m ¢;Jfp~nlc1.e~ a!~e~d~spoo 1!.ipby its Un~r ~ccel!e!J:![~oralmd 5YllilChrotroflll. Tbebeamwlllthe» :be passed tofA[R's; new sym::l~:rol~rons[l) be beosted 110 hi.ghe:l' speeds. After that thi.cl!f:s'l!lh:ing

Old .00 1IeW. f:&l(l's SYflchroboos,5Iorige rings, it nd dll!tedlQ~ dwarf the existing faciLitie'5 wt (15.1 11$).
1

73B

NEWSF'OCUS
pflrlic~lc beem \,.[u perk)d.]C:A~1Ysmflsh ~lllto.<I i~<'I!rg.el HI de~:ectarthmt will iU,la]yzetillK,;debris ~n ~:op[ovi.de ]U:SWg]il,t intothe Sltllte o.fmiltteriilt t.he ~.uomeJm,l of collision, At other-times, the bean:!: will :tllit iI. target,. and it!l~.e obdsw~m be o coUectedilNto a ~.~.e\Vell~ncont!liwillga]] b sorts ofli1l.m::~ei ..These 'I'I1iU he siftad ,on the fly to l~i,ckolJJt:piut~c~n'l.n Ullstabl:e ntlcle-i fOf study. These :iilillCle:icmb:,passed to a SWlr.il~ ci~g,. which ~lO'1/vs re~eIi1in;I.1~ to ~ontrol the speoo Of~IU'C~e:i ,mld create a f,!!!ccisc, h~gh-q~aJUty uh[ma~e]y d)ep]oy dif'f"cli'efl't leolm:iq,ucs. erenti,ng eamp~e1rl~.ent3ryresearch p:mgrilms .. "In each main region af'U'n;e worJ!d, there ,are mllj Of :i nve·slmcnts ill [h:is~~(e,a.of researc h
because peeple <In: ex.c:iu~diil.b()'ilIt Uille sci, .. euee," S<lys Gees<llm<ln."NOlIl!e [ofthe ftlc:ili·"· Peters, HlJemain .g.o1'!!l. w~lif:n FAIR!s online wi ~l~. 1.0 bombard ~'<ld:ronswf.t~~. i:lInH~ be pmtons> fopl)obe: the; b:indrnng or the q:M!f1["ts.

Thep!JlI"tiicles th,)I! nu~dia~etille strOllS force,

klilliO\'Ii':BiI lIsgl,uo:ns, '''lilUlke most of tliI,e mass," Iles@l)i!i.

ties] can taekle aU.the problemscomiug

from tillisl<lJjf!e
COU.Hllli1:nl1lty:·

FA.m:. isuot <ill! aboutlilud,e~.

AhJiti:ic

beilm for :SUb8.eqU~ln exper.irnelIilts. "'fAIR VliH} ave h~Q l!gltq]w~a'bilih Laoo~t~ neer Chi.cago.,lll:ino!$,

phYillicist 1110'mas Stoh'I1;e~ :i:s!ookiJ:1.g fO~~lm to ~'i!Orlf;; ofU~ ~U'.on1~c di8::l~uior.lh~wes lI!OW

Peters expects .FA1R to become dle most ~~nllPorta,lfI.t in ~,la:da.1Jlrnlpllysicfl:"T!hel\e!s W:ll lab real comp1etit:ioll." About 400 hadren fe8e..fltChersfrom ~r,"ntld~l.e"il,il(1(lld-·'i)IMost

half' ofth~oomm1J.nity,"·P.'etef8 ~}'s-he[p~d pLaJi!l. fAil '8, pmgnqm •. r.M Raho 'hf.!8i its sights on
~nottlili:::r rb::e:a quark-glson p pla$m:I ('QGP). Thfu; slate !):f matI(:ll:" ~L~t~mdcr~lmh (;X,!::l"Cft!e OO!l~ e ~ ditlo~s th~u qw.~fks andg,]uons ,"iil()Ve aJm.fi8tfrlcely in II l'lOlJil:pof p~u·tidesr.~itber th~Ql bc[ng ()~mfinedi 1m. l/naJdm::ons •. It [s t:~~.o·M:gln t:tlaJt Jt'he e:<lldy '1IlIli",erse e.xi sted ..s t~ili s fO'[m of p[.aS:Mm 20 to :30 Milcl"Useooll.dis· afterthe b]g baam,g. Pilliliys~of atthe Relativistic srs .1.;.lle<l;vy~on COmdeif (~J~.I~C) at

tie8:~ says llijCrear physic:b'St[)rrlil!~ld 1(].ee~aMlIIn ofA.rgO~]1e Na~iO~l3J1

"high e:ncrgy ~Ild st[l[ag~ rings, '~",hi(!h ,!l!]]ow' you. ~O do cefilain 'iyl,es of ex~rilm:nts.." .P~fI:nui~lgfarFAUt lITi~sinlVolved : about 2.5 1[10 ~d(',':nti st s and e11lg~~ Mileers'l¥Olr]dwide. "We've never worked Ensuch la.rge numbera befOre,,'" says ,FAIR Jlhysi,dst ·,Ingo AugwlStia AlthoU:~lit serves severilll field::;, asrn.'l> b~gy:st 1)IIDg,nmfl Brockhaven Natioil1llaJl L(JJbol'ilI= is :iJiilJ exetie nuclei, FAlR w:m h!l.v,e iBiack.to b[ldcll. Vllilln a bealifl'l {if 11irt~prol.OlilIS,IFAIIIiI'sj)AI~IDA.deteeiClr wi~l probe tory on Loui!i]: Island , NewYo:rk,. ~nd ~ ~im~hu:mpllaJsi.s:Smi,lle 700 sei- t~@if'l~r W{lJ~fJlig,~~~.prolo.!fls. 11i!~!.IIlro'llI~ 1~I(!too IPil!II;W:~s. believe, th<i.t they m;verllre.'ld:y ereentislsltoiI'H. IDIlWllet~l3!nlOc eaniu~d 01QGp, but thoy 1i1~\1Ie yet lfDot tries devised FAI.,R B: ,exoti,c~nw:;lic~l:e:s,earch ail:(rSlbut ex~~>eCts :EAJ l.",villpro",ide hlwm. deteoted t~le ~:d,~~.de: that :ph!Hletlrnn~itioll iom narpro,~.ram..Exoticnuclei IlI!rl~hi SI~ly ul1st!libl:e \'!lfl'SI'&l!te:l' .~ccnl1mey in l!WlI~]il!l.gdo.v:i!I.moms' mal ma:ttelf. S~a.nc rescru:dl~oow' thill!iJkth:a:t isotopes Oiat are ~cy 1:0 :findiog Ol~t tlle Origi~l pr,opcj"lie~. Fow e~mp]C', fA~I. shOiald aUow at th!2: hi~lJijl'b;:i1til,p~lt!tCg ~:tilOOitt II-IIC,(b3oo ofm~l)lt ,of !he chcmi(::~1 c~~mc!)~!3 onEanl~, him ~()Il~k4;!! bea1lW!! ,ofl;!nmi~m a:!J()m~~s'lTip I1l~J be a phr!He tfam!lili~!l~ t .f! Iro\1:d,u~1 ~1I)t jm:. ,,_. ~n;o!1l1! ...'I'fi1J" __ <In,,,,. _O . 'I.J~, AlthQl~~;~ a t7ew ,e~C1il1eID'gi!NWf;lr:e wl;lld~ by tl¥;.-rn of all n~if'e~Clctro]i!t']"f!g~d the:!'l! m,,*I::!l!~C shin~-~I ·oo__.. a.'1 tl1J'-'"""'" ~-, :Q'I1P ~iae~'ttn::~llC~cmp~r~n!res and p~S:8!,l:l"e~t~~t: lh~ ~~,~$;S o:f ~h~!1ak'ed !mJ~(l~el~ljj,'itbc::~trem ~ "Wh~l ls sdU mi%iog is proof ():f tEllis IlI~¥ (':l·,j&ted so~ al~e'r big b~ng.In!a:rly' moretil(: pr'L;:ci:sion.giving a better fix Qn e]ec:u::olls' sl~t:e ~f ma U:~r;'" s.~ys l'sf1e~er SCIiiI.g~r~ 1!.1:]) tuiron amid IlDo~n;;1on the peri~di![.:: blk:~ b~nding energy. '"11HC has some ~~ld!!ca:~Omj no n.oki1l1llg blltl :;l!r,e fm'ged hill ..he cores af£ilt3:rs~ The ;~'n.eav~e:M FAIIRwi.H atse provide i~~.ewori~d's gllill." :F:'AI.R.wiU 1ilPprl)ach ·Ihepr~b!elm.~ f!lOln aJ ek.len~$ have ,Sill even mare 'IIi.olielllt: birth fn most ]ntcftlJ:l>Cantu.pratOIl beams, ~II!Owing di.lferellit dil.'lectiJOn.lllst,cadi of RHIe's 1~lgh te,mpe'.rn:tru'cs, PAIRwu.]~ use high PI\Css:~1f.;e!l, :5 teller estacly sins s.ucfuJI3J S S 1lllWlefmilcrVaJ.'c res.ea:reheil"S to beUe']" :stllJ.dJy the s[pectrosDOPY ,. g~lnm:.'3J r:a~ lIriM~:tS;, or x..;r~y lb~rsts.]:I1J such creating; the sort ofQ(JPFbI111d' ~~.lClIIl'(lll sims I IOf a:rJitihydiro~eFII 1JliiI.d com[,~re :utw~~h normal expl.o.siolns,~I.i.ghtllT1C:m.Cllt:s are bOb1lllbmrded C .llYdroge~ll!. A:UD:Y dLifferem::eSI1l]g~l hel, solve and one. that has 111deloom.b]e phase tlI'"dllsitw!n1" But sl.mlt1lnglllle QG.P '\7!!'~1] b!. no .eanreEit :In whh lrn:mrl:rons or' withp.mtoll!> •.:sw.eni~g~to the lOl.lg~:st~ndingmys~el'jIOr\\f~Y MlleH':- is so <Ii la:l'gesize buti beeo mi~g iaerea t;] ng [y Ihile a.~lti:ma.tte:T:un the universe .. :FA1R will thelleetllng il.'lstffillilof a ·pa:b'tici.e oollis~QiI1II, the t111lista.bhl.Unde,rsl<lllui:ilmrg how these ml:stJ.~ offl~!i 3. "q;M]:itati.ve; j ump·1 mil \:V~.m['spo:ssib] e:: pllltm:ivil: p]3S~llJ;<JJ SfJtnVS Ol'ut thcmsmmds {It'PRlI1i~ bile Jrn.!JIc~c;i decay iIl[() :!'lolnli~th]ngmorli:'lon~:~ bec:tlus'e of its dedi.ctltedi shmage rings: mId cles,. only a.tiny!htctionJ of' wh~cEilmay carry l.asth]iI!l 5lI1iCill~d·ttl II ,r1hYlSici:st5 <Ibo1!lLt the o(r:i~ deoe,~e::rtlltm:. :says, Stoh]k:er. the signilmre of a QGP; S:enw:r aJlld ~Uiis 0[0 gins. <llld .abumtd'IJilICC' ofthr:, ,e[e:ml~lent:saml!llnd ]e<l.!:1lues b~ve 'e alcnl.tlted Ih<ll tDiLey wu~st :Iog P~ay:Statiiolm...anyoliti!li!l' illS JrilIOW; "U,\fC k~]OOi tJ~.c11U1:::[e'lI:rilhys~cs. it 1.0 ]Th1iJI'[on roac:tilons IJet secolrnld. beyond t~lc C(lll!straiJ)'g,ill the as.tt'Qphys~cs. fI()th aJlie lwt .Rese~rd.lers hopew ::>1lep Oll.ti:lilliO ellt~l:e]y abi.Ut~e!il ,oftodlly';g c..arnputier pr,QCClHi:(lni. [lew tierrainwi dl: ;lIintiprotolrnl beams,. which ~:\'cJllnm\rtl t!o.v. This win Chflr!@Ci ma:mm:i~ Til e-y've:i]lJ!vest igatcd l~rotoitype proc CiS80lfN c,llIUy with FAl R," :'>11)<'8GSW reselllfclIiI direc .. fA~.R. will. be, ;<Ib]e to prodim::eiiln.lcll hil.liiI.CI[e-;@Is d~till,"1dfur PIa~I'8t1tio;lJ! video gnoo.e c{)li1sole~ <it no oiiilet'lo1Ib. T.he:yp]a.nto s~dy tilrnle :Stmn g flo:t )'1>1,on ~(il fIl<i!tkC.t. "'TI1~ a.w th~ fllstest tOfK~Y~ h(;inllLo1Insank~. t1l1cl'ellI'IfQrQe~nd the Mr.lIJCibLl'lfe,onl:i'ld«nl~- pmr;es~~. ,s!~ldW)'Ouhave tllOU~!~'~\l"lorld~lg Otfuer :~a:bs; chas]ngsorme of~he sa.·e ~r,e .I)'lliit~clcs :such i!lS ncut[onS:i'llldpmtons th!i.t qu.arry. inc ludi!lg CI~.RNlin Gene'Vfl. ]1] P[lfa:]]c~ ~twill 00 pOfjS~Ib;li:l." •. Se!1~r ~ayl:i. lIi1'll:: m!lcle ofqL!!l:rk$ .•GJI'temlt the,ory does 1'101: Swit ..:;cil:aJt'id, ff~fic(;~ GANlt- J!!p~f!'gn~}.v f'indhlg the: phase U'!l!~l8iti.O:fi toa QGP cxpl.1i in ~hepmi'tieula:r maSSe$ or :spin:s that ~i(l... tIH~u~lor gloal ill be.~'!,iy-~(l~l pliit~sics:' Radi(l~,ctive··lsotope Bean fa~tory ~t the qU!!'FkSlhait m~J;;~ s~y:s Se~l!!Jer•.Andw1~;o kl1oil!.!i!s .• oonfirlilll.iMilg RIKGN ].abi~.Wll!ko. a:l'!lidille J"aci.lhy fo·]" hf!dro~\; ~lii!VC+ Tl~e U~f1ec; t a ~~ewn~te Qf:matte:r just Di.ght: .give ~Ih.re :~!.iowpeBoo!ns bdng. d.~clopCld. ]11. dle up ~.p:rQtorl, for e:~<lmiP'I:e. i!iCcountftlr{J!!dy !!: Unhe:d S;l~ltei>.AHhoM.gh. t~lerle wi.n be ()Ve;r~ 10% Qfhs ~1a8~ fInd 40% Qfiu gpi.~ .. I)hy:sk] sis inlDamlSitadt.3. Ile;WOOBSion tlO l)fmd Otll !cu.di.es. '-ilAINIIIEl (Ilf IV ~ laps wHh 'FAlR ..the v<ldous fac~ru~des wU~ ACQordhlg_ t:~}G'S~ h~dron plm:ys:icht K.la;us

as

NEWSI'OCUS
.~. Eat Oil' aiv'~ffidJ? ~a_ nUltm~leirglie.5 ilime {Ilillllmlf1lse., but ., ~stieeril1lg de~rr (Iltlliem flclrily 1111 m,ay or Iml1II)I lGt life U he~IJ' ~~ep tlilellll~ t Il!~" being hreiilst4'ec:!.lIIud tbemU!l,e of expos1![re •. w,heUle~:by tilLe, skin erfhemouth, Some alk[";; gi s:~;swDlliIde:ri f fe [I d ~J1re:iJlHlfii,ti pi airs <I Dllli ro]e--ill,·POlrticu](tr;. if me boiled ~e,mub. con-

are thiollgil t to be relaeed ro i~cp hJ!1ge in

sumCld ~I'i :Sollithe~st ASiailimd A!lVic~. are ]~!lS alle~eJ'iic lIm.o the dry..;m~ult:edtOir[ti eatenin the;\¥e st Tbe 5i~U'~e fMd ~U:etg~ also ~Il es tracl<;~a:ni~c~'ls(;lir:! a.st~m" ·~m]<imtoi~~mu!1e diseesein Europc:,aJnd Nor!:hAmcrka. am.da~1 ~nfcctious d i.s,e~s(lIII e~dy e bil.dho od. 11M;:

"hygiene Ilitryp(MJm.esia."a:s~fs bow1l!i!,POSU;I~!n,(;fll 1iII~t ~.pos1!Are to p;~:thog~rI s 'williS the ~

~11l.tUll~sy:li.telllllOregl;l~~eiit~lf.

'Testing the Liinle' Betwe,eln To 101 MIIU'C:,h and 'Too Little

IKooping, pi!lalil'!!lllsaJlfnd ,dhIN

Oiven tJ~i:!:1l (lomlP'l.cxlty,. there's ]utde hope til1,U aVl)ii,dl<luce will lrn;E1vet11l'U'II'er.saJ e:~rect!>. A:l1idi1rn:deed_ the e'vk~nce!>o fall'i.iiimixed •. ~Ror.' some children, liying with a C<1!t Mny make: c<Jjl aUerg;iesless ~i~e~y; hereas living w,iitli!, Hlor"C w dust mites, eiUDler .tale~ps.or~illlU'tS: as: far as allel'gy ,revC:::l1lti:onls ecncerned. de:1Jilemi:i~lI,g Oili1ltbe 5>htdy; Willen lit eomes to peil.]1Jjut~lt, M1lnyp!1ys [~ eiaas aretorn betweea how lillie,~hey know

Imlasbe!~1iI1(ioltlllTlon

pl1ilidl,[e

Flis:kyfoods; flrO!m~oddlershll ~he hC!pe!,5o~ plfe:~i!'nUng aUergy

f(Di1'

and \vhllt the.y visce:rnUy fe'at: D~tarll,vo:r.ilrilig ~~riy <1void3!11CJC are skimpy, but dioctor'8 are

YOOlfS. IBI!JIUS ,iJlvo:idallfl(11il' aauaI1safier?'

In Isr~e.I,thc jrikc c'Oei', .!I. chthl);; first: Uucc words ~ M(l!W!.QiHI. [);',!dJdi!, 1!~dB!!MJllb~, The ~,18 t, ~:~l' i.ld~ypepularkoahersnack of pe~m,l~-t'1a.'ilo1l"e:dplliffr:;. shows ,~ car~!i)!)n b~by witillf! mil: !)fredl hair 011 its IP1il!ckf!gi~g. MalilY i:nf;aJn~s e,at Bainba whc'lill they 'n~ a~

young as 6. mOlllt'l1i1S old. 'Salliliba }'n.SiS. becQlue !I.!~~.nlll.i,k,e]yoster p that le~~dbrs:e lhi.!! v~ew-[l1ic~lI1d~llg the IU1lJJHed ehtld in the world! offoo!d. ~Uergy. where S:ta,u::st the United Klngdmn. l3Iud (;a:l1ad;@:ph:y!)i.c~l[m,,m'e: d!espc'rn;~e to ease the' soaring have seen a~1le""pl.os:ion of PeflHiUt :<JJ~~el1!;ies .• bnrdellill of hypera:ctiveimim"m.e respenses .. In Mea:l1itvlmiIJem .hJrae~. wi[h~:mba. meJl:irI.~:iH tl1.e pa.st: [0 :yefln~.peanut al.I'e!~g~es,----,a~iuo:ng the, :m:outJiniS ofbabi!es tee YlOlmgto M.]k, the, I!iI~JiIlnos't: OnUl11110[l andletbal-e-have roughly C [<ute ofpea:unltllt a!.lergy in todd.lers is O.O~%.

1Jli1!e(H'I:tmrt~lde P!!o!'!'!ot:iw,g pCf!~'I~te()lmista;!i!iI!pt10lmi. "Pe~mJ.t tlU(i:igy is so .Iethal; you dlllll't . get a second ,e~.mne'e.·j$iiy~ Patrick .Ho:~tonJ~e ' ,ehildr,cn pe\\1!!lUf.8 ~nWlnl'ey f.!~ ]. yef!!f~oh~ Q!1 'lI'nivC:!1li,ty ofWes~em A1J.!;.Si~~ii!l ~'ertt~l.who in the r1!tiOfl!~~c.tI'!i.lit @!le C1!nm:otb~cOIT!~1!]ktg~c ~1-t,~mh,.e;s. ~~cll!.1!!n~Sffl;ij. li.n!i;devlyh~g ."Uctgy. ~o a; food without: be:i~g c~oscd·1;O Lt: fidlh~.t Sd'I:I. he Sfl)'f1i. "'lI~~roi)'thf!t 'li"~~:houg:illl ~ ~ fheiu:mnm:; and d~.gesd'!l'e systcmsofo~d.e:r \~'ere sedng 10 !¥ca:rsag'o,;' wit!!;)aT~c:rgy risk !ch~ldreJm \l"~U be better abl,.;; to h)]c:!'~tc the l!raok~l1iig til doge IOUl"'!!.IC" "doem~t hold.IJ,f.i"" pe;mut pmteilll~,~h8~: emil!d~cit reaedees, BUJ~ 'f~e til ouglllit thalt hi g:~c r doses may not in wh!lit seems a c[mtrn;dic:Holl, tlli.e eountrles bCWC!II"se ~1:::!1> (lome gr~dilli!i.lIy. as sde]llJtiiHs
d:i.!!l.deep er into hOI\~ envi ronmeata I. cues prompt I!!!nim~une :response!. That tliil,e ~.Imnune sys~elmrn.attacks somethlng l.ike

Esd!edc.l1ill coli bactesia, ;EII s>]ck'ne:ss~ ~nduc:ing p<lithogc:ll1,. "makes sense," says
~iaflpllla;nie .Ei.:se1l1lIbartl'n, ofY<lh~ Ul1:ivlilrsHy SiI::;hQol Medi~im::"wliTho peTIf:O:l1iI1Ledll,Ue:rgy

ti.cmb~'edin1; lNJth tlteIlmted Kingd.m,H. and dle Ullillited. Stflitc::i.'l. wh~re they ,I,n'e~t 'It l!e<J:st: ~,%of YOlln~ GIJiui ldren, A .British stndy4 )leafS 1Jg;oliep(!rtiCd tlmt peall!lMt~all~[c cliitihkctl! lmve <1li ]()~lfCir quality ofHfr:; Umlll those wl'dl diallJctcll;, S;t1iff~lfm,g anxLet)' evcry1;!,,:i;lere, fronl riding the bus k) emisi!l1gthc :su$lCirtrlllrket. "The k[d~ den't 1'0 ttl ca~.p ~j'I\;,e t~lCy shoui'd. ~1(:;'}I O~l~t~ to b~!ih· d d.i'l!Yparties," ~!ly8 Bri~11V]c:~rYi afeUO\';t ~gl aUergy and ch!'wicililhmrij:nli.lliW~o1IY ~t Yale Uui'Io:crsirj. 'Ihey and tJmclr p1l!re:~ls live w.ifh"femand. tl:'r.!lm::llIdclJ!li a.l~xkty'" t~iD@t une:xpected cx.po~le "viU trigg.(;r ~!l.Qdkand even dC!lfh. :F'or yea rs~ phy:si.(l.i!!llls i:n m:l1ny cOHiluies ~~t1ve IJrgedp![rellts til !nmid. feed)inghl!!lh~rL<;k

lsthis <IS:S0C:1,ltiO:f1 accl!cre;aiJitll]. or C<l1l it ten m someth in gah out how fo I) d a I]e rgie :5, devdQP7 :Irs 3, question <lfiked iJrncl'll:<lsilli~)tyhy

st~dli es in~'en OW:I1LC immunol d og:i st K im B,oltom~y's lab farhee Ph.D,. f,bef[;i~."But lIU,erlillsts. :Sl]!rlythisyear, <1. :Bri~jsh team whywo1!lld YQuwrm,ttofligilial r'lII;6"'ivced:t' The Launched tl;e first tritlla:imilrilig ['Or a d~lle(:t commolfilpbin~isn't a ]];ealtL'II thJieat l'.!ruis ]S answer; Their study is rocrl]H~ng4&O hggll~ rha quesrsen aJruc'l'gy ~pens have ~~kcd ris k bab~,~:li llflId < ,oiferi,J1(g pe~nil.ts to bal.f of thclTl~e~veS.mr dec1iJdes. th~'!l1Lw~\lil(;\vithhOlcliins [ftl~nfrolitrlthr;: rest ~lilI someone YU~~iCl1'lIDI~beC"a,Mis(;ofi!'lm~~r Win one ,grou$l bem"'~'C ~!]rn~:rgk? 1l1e:re¥ no, genes or for otl~!cr re.aJoom;-j~t"ial IC';WKlSures s~J~ bet; :i'lJ~ :8 h!.d~e8of food"p ~t. and othe:r hi} l1(flnlli~.~Uynno,ClJj'()U8 :prICI'~e~ns w1\i:it~ [ ~t~!I" SJ]lCrgi.es~{i;t'i the sp~C'tru!:i\ w~~h conflicting blood !l;e'~~~ncJii!rlc"nas l' hel~r 2: (TH2) oe:Hs k re$l;!Us ml wh~herexpo~t'rre il'lpr(;vent.ive·, il~t'O ,S!ti~y, They alert .B cells. \vbuch c~ml,!!rf! o.1)[t~l:1Iti:lbol)d.ies~ot~~.ero~:ciJl.1'l:iose autilbodp Reith] nJd!ng CIIVQ!ll.'IlI'al ieiS. part QI~i ;j\ Idas;s c;aill]cd illlD.\mogl.ol:n.dlnl!: Anil~tl"kaJN~ set' oif'v~l:hlb'le::s C,~1I1shape th.e (I gB)i, !bind to wm'a!stoells mrn.dset (lff8ilh~ monset oi:3!I.lcrgics,: genetics, eczema, lm.ot blown re:m::tlO!n the :nex.t n.WIC the ofielld:ilmlg

ar

! ~ ~, ~,
~:
<oJ,

~:
5

NEWSF'OCUS
rrqie]~1,. c~~hil an al.lergen. ~f11I)lP"ea:r.s. The mast QI~US empty inrlTIfI:I"Irlma!tary diaenric!I.bs such as ~li.s·t~mines the ~loocl]Sitre:~nl.callsinlil; the into c;[al>silc:5Y~!lptonJ:S o:f;!ii.llergy. In the mid- 1990s" Bot:rt:ml,dy. nmv presi» dent of Wel.l.e,s~eyCo][e~ei]ml MOi.:sS:lIc.hn~ seit:l:s,.beg~nllre'porting 11 n101-cm~!l."lllc~d ·pg.c~ knews w'het]n.er this is hl.le ~11:lJmna[ls;, BlJ!t :U~;l cells ~nd aJIIiJl1B!~S~the: ~~~rgy 3.milmd!y, ~:g.E., can be stimllJlated with !>1TJa1l doses ofcert8l~n ;!II]l\!rgeIThSgllvenili'U!eflllli~1i:ClJ1IUy. whereas <I pro· teetive <ll1llti.body,. :~gG.comes f"ollw~rdwi~b 1.000r_ge esesgivenregularly, d Mays AlhHl BCio~r. Oiiped]!ltric aUeqJist at the Ulliliver:s'~ty of Malllit;obll inWinllipeg, C~n!lC!~.Ars"had's ,own .~[k. I:im\ile'l'Cr; 1.lJi1.detScOirct:l. tensien the: be'l:\cveen W'iroidi.ltlce and e~pos~lre.

expos:~~res tl~a;t m.B}''be delererieus,

thilillrgotber

$amenot Jmifl!\I'c

a.voida.'I>oe :studies:ma.y

ture in cleUs and mmice;

Theinsrmme At

re:spo~,s.e to .1li~(n)eigJIjl.sub:stal1ce' shiflled ils :

tJ1C dose ohh,'J.t 8ubs·~atl!ce:incre;1ll~.ed.

~QW

de ses, ~~.elf 1.<Ibsaw 11. d~:H;icTH2: respoase, High doses :-.oetoifthel:1ip !ii.ide (;If The bile Qf Wjgllid: e~perilmlent th eimmun 13; ;$)" ~teM. i1ctiv~tiO:!'l! orrill. S~nt:ef.Jn years <J!O,. Arsaad began fiQUowwhich served .SiS :S!. brake on Ti~2.[112002:,. i.rlg ~2.0 'iliihf~nl:S enthe ~8h~ 'OFWijighll', ;fli self!l~i .• E]s~~'!Ib<1!irth;I!l1I.d BouO®l'Jjly['.C-'I,"'C(;!]eod~1'! mice rM;r~~ ~t::l~ndS~\l'c:m~ k]]CI~J~tefS ofT th~ Icoaslt UHU ~h~ :nmc: do~e:p~tl(;fI'i!. ]aQld 'w ith .a n ~dju va:llt, is! silib.s.ltanc ei ~l tlhe IC m,rir01lilJMC nt tl~~tprimes the t!mm..lne liiY s:l(;m. m- :re8:po.nd U:l' ana~]el':Si(:n. ;"We l'lt:,m. (i!OIl' f li:'IH)\;V" M.ihfU: '$ bch:u~]d this, .ss:ysEi:\le~d)adh. Te:sti~~g hether :soll1leitl1~i:11Ig w similae OC:CIJfS U[l ;peoij) le, some <IUe:rgy-rnueventiJoll siud]e:s uncovered a be]~~ s:Jm:8iped. c:t]rv·e. pSII.ticulfllrly with e..x~)Qst]re pCils:: norelllcnon at the 2iel'O~ to
close end,
til

accomplished, Some phY:S]c1.ml!> are [ooJicing beYO[ld~hc .Ievel Qfm;lJj)oS:l~re2 and ('ons~,deri:~ hmvroQc:I IJmtei.m; ~et 'imasid,c the body. In 2003. ped~!l.tr,ic O1I~.~.,el'.£;i:Slt Oid.eoll Lack, now' ,1t: I:(;irl.!ij~ Co~~c~e:L(JJilclon, l"Cported in TI~e New'l!Ilg'laud .J01~·':nai of Mledicill'c that: by the 'liill1ille they were {I months ,olcl\. 2:~. o:f' 23 pt,~&eJrnoo~en; with pel1Ji!1l1itilll~.y had h;t.di erearns CQn~ tll;ini.ng pe,HiliUit oi~. '1~licih1!l-etypic;aUy u;8~d for dJi.a.pi:lf rash, a~plioo to their ~ki~t ]n a eonttlJll gmtmp of I.40child!ren.~'I\i!e m.l.mbe:r w~s

:59%. LflCk believes the roure OIfle",pOOl~IJt;~8 kC:Y"__'.'1poC~nc:aJUy. that' skl~ eJ!.p081!,1:~ in the ~d)Rc:!lCCofi.nges<lklll. ratherihan illge~holii!,of
sm.(l!.~1 oses, is behhild gm,.,.filiilg rates 0·1' d Ile!l~~ntaUcl:gy, ~'ltwould bL:":. high~yilnpl~Ii1U'[.. ble to nle t]~;8it Vole 'veevatved I.!~ a speeies SlO th<lit rnfwe m:<Ii'll\'!: lay amounts of:li"oodLhrm..l:gh n thegJll:l,"ml<lJlergy dJevtCl.OlIls" Om: ·effort: to settle the qu.eS!t.ioll come::; in a study Lack lauuched .eal:i.y Hllis year; Funded by the U.S.~based ~DilUI1lUlle To[e]"~ aace Net'\fOl1'k (TI'N], his nmdomLzilJlg babiea ycIfL1Jil,&e'.f than I [ mOililllH1!i old]to :rece~¥c pe~m.l.ts in diffe'I'e,11IIfomlS!. SlI C~1. sp.eil.mJ!1 ~

srrm.l,g ['.eacooIli

with ~mv

Of

:IIiIr1)od~

erate doses, and li.tk~ or !m10 reaetien !I:gnan at tln.e liniglJ.dose end. Some foods: may fall 1!a;1IdCF t~)tis I'ubrk:" tDO. :11111 2[1H~, pedi atric asthma <l!n all ergy d !l:peJC~:ali~tJQhnW.:nl'leF oflm.periil,] Co~~e';,e Lo\liIdon deserilbed ~ eohmt ()iflbE'lbie~!"lt b~Sh risk for egg allrel:'gy ti!1d ~o1lImiiled tll.~~r'fue,f

b:Mn~ ~.i:'l:edv.1i:th bllll.l<l1M,.

0]"

no pe<l.11Uits :UlJili.~.

of f!I~.il!t <1.1 diet duri li1,gpr:.t\gii1lil!ncy;lllf~j;lts ern

who!!l~ cgrd blood l@il!d~~'f;l ~O"l;v~~t '!" ]:l,ighest o k;\I\';I~of ~i:!tibodie8 to egg p~lei~ls'W'Cfe least ~ik;clylQ cl'_perilcf!ce {IU~:r-gg.c hype!]~nsi.livity. su(:hml ec.zc-rnl1j by ~lli!.en!l1;(:iI.cy \VCliC6 loo!lths old. 'fhosC:!i'1 ilh ~1idrange antlbody levels Wl;:1iC ~~ MostllYllersews:itive, Theevidence~s sng" g.estive :ii!~~hoo~ [I remains UI1C:~ wl~dle:r .(;1 pregrlmwt \\'''Olllaill'S.dtlct C£l1l.i:fIII]U.ellce; aWl'ergy un ~:lm."moom (1h~]d.. StlJm: stndi.es such as Un,is QI~,e have researehers ques~:iolilJi.1lig"wbethe:r we CmJll ~ ~'e'Bllly pl:event exposure" camp~etely. sa.y:s ~ lJem.ti s Ownby,llpedilltrii,e allergi.st at the ~ Me;dlilcal O::.H,ege 'of Georgma.in A'~tgusl<l ...At ~~ast ·~.l~l.ftheoddleJ,'S hil::~se(;lS .'0':1:10 ~ll;[J:¥esnd~ t ~ den[)'n~u.c~cd U) aJ food weren;t kno.vm to i' 11I<1iivee:atelllit before. But bec!i;u.setJIila]]eQ1;Y ~ cCllu:t.develop W]dlO·ut expo~ure' t~rM •.th.ey 81].1l~~1:oo.ve eoocmnmred prnt-e'lus, SOMe'I'\r!lCTC. . ~ Foods !lo·t knO\JI,'Il to cO:rl!tai~ pomlu'ts nl~ b~

ttiey;[c.3 years old. and tru.ckwho de\i'e~op~ !llllel:.g;~es.Ab{l'~t 200 chiM¥em! !:la.ve (;;nl'o]]e-d !"IO:tlir.the!@:~dY~'rli~]la!i.t 7 yc~.r8. ~Ig,]t. n Auslrn: lia, i.srui:'i:if~i~:g.~.simdar i ITN :i!h~dy,gf g rass ,. e at •. and d ust-m tte allc[.g-y~r,,;~ru.hi~lg 2:00 hi gh-l18k babies aJiid giving half ofthl(;!1l d~,]~)" doses of tl!U(;l'rge:n
i

dmiP~ under the H)~lgue+ ·'For pe>op:~e Il the O ol!i~~de,t.hl:s; .~~u.1I1JJd~li!lr:e ery adventurous v
slu:If," ~y!! Holt .. But "aJiThYeaJr11y fears of 'Obi Illy 004 Y01([ 're going. to erea t:e havoc' " by exposi.rlig. hi.g1lL-ri.:sk b!lbies to allergeus IU!IVel1't yet 001111.':['.0 e. RiesUl]ul are still slew b Ye.!l.H oft:: Wmbotllml the Un~te:dStates and, the Ull'ure:dl K:i:ngcl'Qm. phy~~ci,ruli1_s nd health ol':icia]s are a reool.l:s:ud.cri:ng gllidel.~IU;:S. Urn! ellClOUlrn,~e '1Ij,'"~ ents to avoid giving liLrgh.·r.isk cl:llldlren poren~ t~:any<Im,e~eIillilo foods;thr::,y may s:l\ili~:to <I mare ne'l!litrtl~; $~.t1nC!e, .B:m'·[;ul ~Jt:in~ler'!;.'ous a.bou~ poonuf," o1I:dm:i:ts. ne ~eol!derin the J1:e]d, o lil1!a.gh Siil.IU:pS omit.of M01JJnt Simi ~Sd.ool of M,edic~i.ne in New Y(]!rk City."~: doll! '1 h1i'iic proof.lj1itst haw [hils 001:1 Of~Cf!fi(; thllttheres smnetld~1.!diffuroflt aoo'l[tit" Aslkcd by 'W"Or~ 1i000~r~u'S ""~l(.Uhe;~i'Ou1d d:owm the ,child hi :-lg\Vn, '~P~~. ~, .~ w~'M;dd prObf~bly ,w.void ~ pefmitH:.:" At the: sa~'.e tr~"H;~. S,<:Jilllf.'!!.Q:f!i ad!mutl,li ~(;I.ncver qui~ekalo",v~g \",~h~t ~(j"l.dJwse,"W~mtever w~'~rle do:i:lii,g i8.l'i!jO~""'Oli"ki~.g," l\I.e sgu~s. "lbecfIrl.ise rh:ing:s h~\!'e ol'lly g.c;rtten \"'l)rse~" -:JE'NINIFiE:R COUil1N

Om~il~i!!ent,.Scil;![!M:s ~r'~tflS!i!l!I~ \"~ftoolf ·~xpQS1J!lm ~o IP~.a IllIUlts, diust mites (~br;!~), iHu!lgra5l5 (.an ile til
preVfii'Vt

all!er9i~Jin lIIigh-rid':uldd~er~,.
i

..

of El1IigJ]and, Tll1. e chi.[dn~;rll, 11]] ;rut M~]I :ri:sk pi .1I][e:rgy tlilld I.tsth,lIiIIiLlI,.were p1!(l:i:lil<il ]~metecl,,·

.expo,s·u.re gr:Ol[P or o~l.(:;wrufh notlitr'l.al ,ex.~o··

SU!feS. In th e'low~.expos llJli1e· gmu.p breast· rocdil!lg mo~bcf8. \~Oiided [lOW\" HliliIk,!;lggs" ~ nut~. a;ndw~leat. BKPOf;:l[W tobomsc dm~t mites \·vm" r.edlilcoowitlm. pe!'lticide~ flilOOdilnatj

§ OiIIe; pl!llce: In 2001.

the US ..Food afldDn~~: !lil Adm][1i:str.ltlOil!l :rep~mdl thllt 2.5% of fcod.s "" ~li~vey,(.':d that did .[!~:t li::npeai:iltbt~ on th~ir ~

§ Ilaibelstested~~m'illc

fb1f t~~l. ~"Ti~~ 1~r{!!bI9m ]~th~ .,m~Ua1IWi!!Cll!!lts ma_y ~ be (:v'ell 'm.o,rc; a]~,er,g,ent,o th~1l fhe ~f!.rgle ~ !llnOij,nts," .~ys (lIlIC~:g.istllaJs:ml Arshad of ~e ~ Universi.'l:y of :So~dh1tmlPtQIlJI, U,K. 'No one

halhs

·of W~.g.h:t, rnhad thoo:ri2ic:s. bCCO;1{ISe several A

I~ '~'lTheirirlit 8 }~~f~~ 'I!he~e ,eh:i]dren "".,;ere f mn;:lyt)() SiwFller;;l,Uergit:ls a~ 1!iI~!1;: C{!l~lttQ] gr,oup, Umitcdc~lIo!\it:!n} \~rIood O~ th~h]il~

.a~]{~~ics'~:re t(lrgete d simllJh~n1JeO'l.lS~and becal1.Ise t~Je c:!ilildr!cn :!1Hc:rcd eireaM' of small

NEWSI'OCUS
S:t~llley 's ~e~IIIi app,m:1enUy acecept s this dramatic abeat-face ..AU the surviving <1lllM1Q(fsfrrom the 1996 mild 1999 pa[pcrs are e e-authors on Ulc new report, And G~mdhiililf[oh,m: V]SWamlit~,laJn et'the Il",ederal IJwiiv,enitJ· of AI.iII~(HtS ~IlMll[jei,6" Brn:z~il, who W.7l~ t~,e first Ilutl:iotofthe ·twO· e~rli.ler IJ~PC:r.s. 1iL,~l'ees"v:~~hEd\\l~aJl1ds:that "the jury is elll t" 011 \\\h~!,ji&a:er Uvyngg~lts ,1Ipplyhl iifillj' fonlgillgii'ln]m~ls. ~'One M~~llbrethlllt thi~ ncwp'<llper sends is de<lir: We~nMst: be more c<'I!)cflliwhh di<'!t.lJ lIfm]y~i(j:·he .saY!j.

Wet alm,d! dry hird5 Phys,id$~8f~['S,'E]8CU;S~cd the: notion ~fll~ta:_1'!~d IIIals perf~rm U:vy mglJt. se !!f,ct\i,(;~ im tfu!1;
19:$.0$" but obnailrnJing d~l!ita o~l~fl'ge-sc~le !llOVC~~~UlS of ~n$~ll~!.8;i1JTh .~.Iiii:S!tliJl'al,en'!;'iro!lmcnt' \!!!'asll'it 'ea~y at: 'til!f::lime'. Whelm. the 199:6

aJb!lh:'O~srep

011:esme rOut, ~~leide~

{lIfo

Le'lJ'j'

IDlolWalnldle'riingAllbat:rIOISSeIS, C,ar'l Abo'lut Math'?

R~IPIWlcIDiatillillgaJ dE!l(adll@'·~b:!I!l,tJWldy olf sea bilrdis,j a 11iI1E!!W P ort Iq U!fl!Sti~IIiI!I, a pIO'~lna,r I1I::!' of Iilow aniimla,ls,....-,t!ls eU ss fi slillingl boa.ts illlWd poop~~5e\al!'icl1lfGl!ffood w
mOld!fl!l,

flight:!> ]11 ~.1fI;ilJlJulls I'lea.IJy took off aJuong elOo~o~ists" That IIlUb]]cBll1.0n Jrn!aJS ~beencH:ed more tlili,lll .~ OOilme.s. iRe:sea:n::;hernI.l~ve since df:'5(l~':ubetll Le:vyn:iglins in jackals, spi.der IUQukeys. seals, ulicroscop]C Z.oopli<ln~.to:n. i1lffi,d evea by It'h]u,i~ilg vessels and lrunrer!;l;<l:therer tribes,

A~~. this ex:dtenl(:;nt pi.qU'ed .EdwOiIrds,'S curiositty ]1.1.2005. An e>oo.~o.~'iico1li. modeler, he

had just landed a posifioil1l wrntll1t~,lC .Bf~tish

Ali1I!U!rc~je S urvey (.ElA S )in C~1fI b ri,digc"

'lI.K.• '~lm.e ~oi.iir,ce: ohbe il,Uiniit~o~s dati! a;ii!,iity.wd by :St~nlley. V[swil~~a:th~i1. their iind A'5.itll nlI~1l'l ~l1igg~g~.th~ W~lmd~fi!~gaJ[bu,- 1!rti,c~e:tl~:atth(;l' tagged birdls alse tb]~()ij,~d C;QU~~gl!~~., fldw"aJrd~d~r;;idedtQ t(!~e a closer ~mg~ (DiQJ,,!'wt~'Q/~.;G'd(~',l,")Usa falbl~[{!!usf~)li;;r. t(:vy niglm. : 'look .:It tJiu;; ()rigi:Ella1il sludy to l:!i!ld~f8tand tJ~(; napping h:s\'!fo\'lyalrolmd ~:h;ill woddw:ith~hi';l This 8tr~ltc;gy C!()!J!d:~'\JIrk\,,'re~~'1""hc~fOod method~~ 1JiI~8~d•. ~,(llffi) of its 3. -merer pi u~wi]i)g~pf!n~ the su:ppN~:s are ~o:!l~cf1n'ated~Il ~ fewp~ace$b~ ]'992, BAS r~::lj'eali"Chers ~if!dOIfi!.e to ~g say, in l'iiCh()(lIi~S,offislm ,o!rfidds ofAO\!i!C:rsIO'liilgest of any U'V~ngbird. A~996 re:po:rt mrdls.li~lJIld in SOIJtlilGool'gia and a~choo aJ
seemed to uffer clear proof of t[~e 'bini.~. cnd;1)I:ralm::e: It (bulndthat: the b]rd~ l'ii(lITl(:tnme;s· !;o{!:redfbr as mRJIlY .a:s4 da;is befollf:: kluclmi:ng d)OW:Jm1on w~lte:r, pr,eslm~:fIb]y 1.0 C<l!tc]~,f~sh O(lr ather food. Ollie, of the;f~rrs:[ stll!d[e:::;ilil, l:vJ,lich :re:card'i ~lg dev ~ces tracked auj~,ual mov ements. Ul,e\vork also b:r(mg~mt <I ]iU:le~l:nm1!'n D,<IIthe~;l,1<11ti,cal~:ool to bear on the study ot aJlli]m<lll, Im:<Igi.wg. It soorwed ecologists that a :.odel, of :rrm,u!:oMl. Moti mil !C<III,I,ed 11 Lev y fli,gliui1dc:scr~,bed the wtuy rnJbUroflis.e.s ~eil![icbcd foM'food. 1m:pirod by ~hC\'i()irk of French nmthe ..
l!1I'iI~tiCi;lIlP1lld

~Icte,,~... by ~1~nyshort hops. with ITlM:ch ;ed IO.~J'Jmla,ps. on r.~fe (}t:'C~S;iOfi~. pr,!mysici.st.s '~01iive; hrng used the: ~'1af~cm iltfe:'> b~h~nd L cvy:f]lghts tQ pred!klt hOi!,'iiplitnid,es m()v,e i11l.·~iqu~ds.!)nd lm(Yw ma,'ltell' spreads in the M~ivc:r~eJ fur C]iHI~p~e, And ~nera~~~y;d:ng I:j;g(; reconk:d aJb.aJt r,os;s datia!, a team :~ 'by ed p:l'iJ,ysic~st HI. Buge;ne St:mJIl:~e'!iQifBoston 1I11ivm::shy

Levy. Le\'yfiIIg~Us are char-

enu) COllcl.lm!d,ed

:~mal '9':.}()' NallU,,€

sea or bare Ilewly des:~gMledde'ICc~o:rthat: rog;ii>terod eongr'OUlld In bet'lvcell" bmdeCld.11'II a 1999 N,rU'f,~,,(j tact w~~hs1i!ltw~ter to ~. I'eg ofeS!c:lm! of f]'!,Ii;; ~nricle~ S'I~n~ey's gn:)I,I1P louUiil1l!ed tfhe iI:liite:ore'l:biw1'lt retrilev.iillilg t~ledetectors mJbO'!J!t 2: '~eks ical belle~~lS, offorngi.ng wit.lm, dil;e Stf.'llj'~egy ]a:ter !It ~i:lJeIh.imls· nestIng sites. After a BAS ,E1nd m;serted that deer ,Simi, liJtumfijl.eberes: fcll.~ gm"OIJ!l.P lIIl!eluibe:I:'lllel smn.eone c!iI1l~ll.Ul BU~e;Bm kllwed.EI Levyt]]girul search ~<IIttern. ~~lteres'l!ed ~n ~11!ode:]'ili1l,g mrli ~miSJ~ 11lOVe,I,ti1.elUs" BAS <'Ig:reedlo pa~ovide·the dieltecil:o[JIS·d'<lila .. Lastweek, howeve:r, a new stu!iYIJ1lveal!ed (J<II:WSi~ll, both tJhile 1,996 and I, 99 ~li:ffi)o:rls,. ln 9 for their ~mil,]y5is,. the .BU teaminterthe ~.nida,l<IIlbtlltro$Spaper, St;all~,]~Y'Steam p:ueted"wet" sigmds as lnOJlIDl)enl~£\\iliLen~Il.e w~::ilill)lte[pret,ed. k!e)" data mm,tlrn,e b~rd5, says birds s top~~'edny]ug over opense iJ, and Ancllre\M .Ed:wi'JJi"ds .@ftherllcific Bio~o~IC:l.d Wll.bbed II ~l<lck: :IT'On1i d1.€w(lte,v. The time: in S;ti'ltioilili [11Nil~a~mo, CalDlad a, ~n the re anal y. between \\;1<'18> censidered to be; mgi'nt time •. sis by Edw-afds ami c,oUeague.s. re[IJO'rlJed in with longer "dr y"'i,:IiI1 terva b :!ill Jiili fying the 25 October iSiSlIC (JfN(;rt.u.I"e. the ~otlgest ](]J.'Iger distancesin tli1lc alt. Vi.sw""n".t~.liilin. ~ night dl'DIJS from 99 Im,Ol!fS 'lo2cO hours, fur thMaBU graduate ~wd!t:~u" StalOOlcy. and ~ 1e.x~mlP'lc. More>over, u:<ilns an <1J~e1!l1l] ot'Sta·· their ic:o~'1i1i.dh(m~fallnd a "'Ilop,. h0il' •.. ]()Ji1I,,~ ~ ti~~'ic,fitests Or'! the: ]996 ~nd 1999 p!l'~t~~ l jiulm,~,pj,helP ••. " pau~'fli11 amo~\~ 'th~ O\'l~ba:tros~ m the rescare'en~shO'w thattthcbi:rd, b1!d:mblc,· jOlijrijlC:y~. W!hcn they ,gr!l!p!l~c.dt:h~i'iC di!'!ta aJ ~' w~y:,the prQbalbiHty fQf a; j t~n~p f ~. e bee. ud deer data $t~'PIH'~:'~ f~(':r ~ea.lich p(l,r~ilcul~r Q 8tm'~lCgiesIc:qu~]y Vt.i¢II, .Ed~rd~ gQC~so' f~r a sp~dfi~ dh;'t~l)l~e seemed H~ follow 1;1! ~'. ,fIS tQ gay th:a!t !lone Qfthc51,j'bscque;nt sn!d:ies so·c,aJ~ed p QW,e!r-la~\V distrUiYlH!on ~i:lil '!i.~dch ~ reporli.llIgani ~!l,S1I .'levy nights tlll~t he: ~l;!IS mostJUlllpi$ 'iVC:re ~I'y sh(l!l1~ ~nd the. ~o]mg.er~ ~: soen <II.'!:: ., I 00% COll'l,fil1Jc:~llg:' jUil1lro.pwns. t~lerarer its ,occura:,elme. 'fh~s type 5 w:uth rnm1g, stretches of empty

NEWSF'OCUS
of' prObalbiJil:y d~str ibl'lt:~i]!IlI1 '1'1\1:(:: dcfiwitiou (]if a L~vymg;btpallem. Yet EdlwmJrds:netieed that t~.u.,:first: find last rn~g)ils, fO!r each bird 'were SllSp[ci!OllSly ]Qrwg,. Wbe'n ]rueremoved these f1ig11lIt:sftmil~,tiile Oif]~ml] ana~)i'!iis. tl~ll,y evidence fhrl.evy f1I]ghts \l<a:ni,shed. T~,lI,e eliucher came when, dmin~ a,coffee breakwith ii, BAS ,1li]lJ<TIitl1os:s !'opeciilJi st, Ed\!;I<Irus~.'eIiI1il16dabout atti, tb~t the BU~e!lll!l didn't k]1JjO\votlbcmt For; some of dl,e ree olided! tTip!ll. some of the birdJs al ~o wore nld~:mel1Ja;ryloc'l,tii()!l ttaekars fbra

rut

V:iswanathaftll~ wasn't used i.]] the 1.990s. SHIl,

lhe Bl1;tllys]s removed from thetwo early p<lper.; the hlst bits of solid evidence for levy nights. Those papers lln:'l;~ being retracted, not however; Vi.Sl'V!iffiHl!tluln Sal)'!!: thai ~il.e and the, other o:,rigi:l'la] O!i:llithors ~eri.O'moly cOil1s:ider,ed rel1'ac:ti!olls bu1: decided t~l<11ttlim!e ItC\v,ula[~sis seli'vesU tl~e needed public cnrreetiea, dIed twe new (Hl,per. adds that
re\'ie:w~rs

Ro;ry ~-Iow~eff,a!:'l oediwf

.n Naiure

Wl,lQ hU!ll1cj.ts peer-

did;~'teq~U~:i!~:re'ffi'l.ct:io.lil~s. ithc~-. r c

seperare s.t~J:ly~W~Ic;n dw,flm8 .-.~dhts colE

k:~gl!ii:~ 1IIt~h~ :sunC)l p1!.t~!lcd ' dlOlI1C df!!t'ai f10m ~h.e <LvChhre:s;.tJ~~y di scoveted :rlU1!It much f~r of theitruiU.d I'ong ';.mghls," t]n:c b[rdfl h3!d neverIe ft f~e ir IiiICS~S. S jlrril'i] arly, thelast "flights" ~e:ndedto be mueh ]O!l'illgCili·because tillC ibi:OOiI' hadn~tunm:edto tI~e:ir I'CS:~~" 3lndWCf'e ~~:igh aad dl'yf:(jl~ho~rJl, .F]:iglrulsrecerded as 69, 67. 44. 26:,mu~1 hOI!J;rs, in 'l::fue QJf.ugi]]jEl.~. 23 l:')'aJpe!l" were iH;tlla.I.ly ,~]~.4 ~.~mus (l·r shorlicr, :J;omelinlcs, less 'l::hml ,ml hO'W". ]3dwilI-dlS,~ndlli:s eolleagnes <II so jo]~,H~d with the origi]1la~:·.Btl <I,~thol's to rellJeat the s,eil.~bircl sHldy. dl"<Iwi~~lglllpon BAS da!t<l taken ~n 1004 from 2,0 Bird lsl.<!lllldiil~b..,.

'orig,[!laJ e ]~im$;;" he ~ays."

Filum ,j:atkah
'1:01

''This isan 1in:nllsl~,dci.l:Scinth01!:t m.w ~t!,dyli.c[l~1 erhndsand a.ISi.O new diflta became m f!,,'a:it~b~ethat ]~dto .fJ re-evaluation af'the

I&1dward.s: '$ re ap:p:rai:sa] o,f ~hetwo N(:mn~

pallP'e.iS b:.Il'1 the Oldy rcoeln ,at~ack on Ibi:(l]og,. ica~Levy nigMs. Bdl,t1viQ'I"n~eco]ogist Si.m~O'~il enhameu B QJf France's 11I3!tiolfn.aI reSle;![fdia:gency. CNR;S,il1l MO[ltpel.Uer has t1illsoI:m]]ed into (][lc:;st~()li1J the: bem;::f'ils ofd;uis fo:r~i:l1l1 ~)rutteTlil... 111 the August ]ss,]!q;eof Ecol. ogJ1, he: deseribed compH~el' s[m~ ulations indi'C:i1;t~n£ fhlltlevy [I],gh t-!Sty,~ed liUlOv,e~nen]i:!> lI(I more efficient at s,eil.rcl:ling ;t]iJ1 are01L than isa ,rari:allt: ofd.lIss:ilclIl

bee5

tresses e:qlmlippedw:ith more soplmistiearod

IlntIiilt:ki:mlJg equipment. The new study enn~ firmed that Slllll1k:Yl1 team had been lliIli filled.

~ "Th e: Ikl'iltd s arc'll 'I~pcrfOtMi J@g 142 L ~vylli.gh'ls\vl~ei1fofa.gi !1S,"

BnviWl11me1m1i;!I,] Mode~~~llgth~ Uni'\I\el'sity ~t o;fS~:. A]flI,dil\e\'YS in ·Flufe. U.K .• the ~pp:li:CatiQln ofthe Levy f'[i~hl:: oncept c to ecology Wl1.S ahvays "a bit r<lir ..fel(~h.ed~·'''h$:ma;the.~ci~ eians U.kinga s~JmplistUc~ool aJold! pl,'etendj~t!': ~t]!!I'elewilit to tIme ~;e:<'l~.!;~mrkl." s~yfij. The he ~dea thllt ':for:ag:ins iHiI'iJililll ~.~ con daet Levy flight searches, Dr any Sil1iiLili1[" random sei1i.rcim. str<li~egy,i,!:ili:Ore5 tlmla'till'il m!I1 SLlS!3 the;ilfililtelli!enc>c il~d experience to guide themj,Buck~;nild Iaidlds. Butl:llot all f.1ic();log~~t~ ~halrCth.-..t d!ismi::-;slve vi~w. Th~ymai~,'t:f!i:r! hat some .Levy t fli.ght studi c;~ m ay be \I~lid. ·'My viewi s thil;t the .~Jb~l.T(Is~\\iI()rk miiY\~~rn b(;n~'il\.re", bu~ it: has pl~)I~d.~ big rn]~ 11m! stjmi!.l]~ti!1g some rc:S!U:rs:oQd suhseqI,]JcI1~'work on 'I:~e who]cJ issue of"sem'e:i:I sr:ro:licgies and own,]llm1 be]~~vi'or~~" lHlyS ClmdstOopl~e.r Rhodes ~f Iml~efia:~CoUeg.e .l.cmdoll1JJ, who has reported H13.tromgi.mgjm::b.~s mwrform. l.evyfli.ght searches, Andy ReYJi1lioh!!)i of RothiUillil::Uif!:d R.eseaJr!Oh in Ha:rpenden. Ij,K .• is ,equally a.dmnant that Levy fl,i~htsflre <I useful tool. fer eccl ogi Si:S • "Thea ry :shaw::; that l.6vyni!]ial~:s <Ire ;11good 'i%'ay to sC<lJrc:i:1. M.y feeling i.s that <I;n;~~ ~~a:s evohn::d to dol:we l

; Ed,ri;.'<itd:S 8<I}'SI. ~ Eti'l,x'awdsthen tcok iA~(I!h~r

~~(lQk at thc~999 '!i1i'o~:k 0)] Ib~m~ blebees and deer, H~ fO~fld oth(;r dat~ ,0 f quc;stt~'gl~bh:: rele --:110'0 :if V@IlCIC to Levy fligl1it~.: The deer ~ '·fO·'ia.g~ng·' tjl'1lu::s !HUllyzed ~y -J.S![I I ~ t'heiIBUle.a!:m, fOol!' example, tumed outtCl be:. t.'fue amo1)J1nt IOf -200 itinm spe:1!Ii1eat~ng at a locatiiCfwl 1

best po!S~ible. setlrches;' he !llays •. RCYfi'oldg has tb'1i1fid L ~vy flight ilctivHy ins ta rYe d fli~s ~e~r!(:hi~lgfQ!TCood b~!a
cOllh!.incli'

-r

~liil.'the!.· ~h<lnt.~.1.e ~j~nesJle::I1I11 tr.f1\1ie I~ !!!:Uil;1g b et:we;en feedi~.l.g s:it.es.

-20(1 -!L50 -100 -50 ~ .' Mo.reover,.~m. ~th the .~ 996 '. and 1,999 :su](bes. t~'l.e BU le.Ulm, .!'Ught pat:hs .• $;cie:l'dim have :5,1I9g:estechhat halm.1lt:SI!}d a. sinlprn,e .g:rl1lphi~,~l 'IMagiiilg ji3idka~$ be~5arlrl e'OiEliiI i3i~: f~llirtg bnat5 8 appr o'<J.ch W dem o~:str;ue the 'Iioll~~,~ LeV';'·mglfl1: ~tb'!u~ {cOO'!lpliJl£r$iT!lilIlatlon, i' power-law distributimli tbilt si:g~ ahwe)',wIliKI!i is rtlndl(lflf'j, lliIotion lliI,al'iked Ib~'s:nrDrt ~~.i[]ed Levy ,nig~t~h (me that "?s :'llP!!IrhS [lirild ()Cra~ilml. 00Ii1ge~~l!Imps. 1 o sm ce been ·1IPiP hed by otl:le,[,8. Hil it[lckllJ!lJ~I,y'Se~ of ~~mlLis' m.Qvc~ ~l1n~nts.l3~l,s.ay:'i Edli\f'll!~ds, tb(; Slrat~JfY can. Bro~1I'ltiail [1JfJ:rjOI'U m!!)lti()~. More-(wer,. ~tm:ke.s a ve:l'y close ~n!}.lysi8 ()!ifl:i:le: ; o.fu~n P,[(!dllCe ~ sp'ufmuscQnd~8mn.of dilt!.i.to d~s;ti~,~.t!~~hthe :~;O typc~ OfMO'\iU~ ~ L~vynl:ghts.I:l:!d~i;;{_~ "wIlen Bd1i\mrd~stal1:ilimel"l'tS. "Bgthmypap~[' ~lm;d dw!lnlg~g paJp~r E ¥I!: t.ic1i]iy C'Ci!np~f.~dwhetllinJerapQl,"l0:f-l.a:w di:::i~ tt'.~b~li.Qll fi~ fhe bwnblebe:e: aFtid de:{:l: f\i)r.~gsl~!owH~a:t [t:'~1C U:vyfli~h~] i\;o~ce!pt i:ll ~lot likelytQ bct1!s(:fu[ tomm,fliIpe fuf~g;i~g ITlO\fc;.~i;ng . dat~ bet!!:Cr Hlf!~ ~on-Lj~vytmi!i'li!it distiia . ~ b1i.l:ti,Q~lS]t dlidn't, •. me:trl!ts hili InQ4\5t SUr,U~l1'i)llg~" sfl)!slk:rJIhllmo~l. iii u This type (.lit' sopbisHc,f1!'cd st3JtisHG(I:~ 'TO f)tal:i:::;dc:i;8!ll S~e!pheililBuclda:wdlQf tll.e ~ C entre !ITOI!' Rcsml~:ichu~HO H co.1ogic~~, and $: I~mdel cOlmro.pa:d SOI~,.!lote Edw.m:d:s l'Ind

by ra.d!:fIr-lOl)killg fo·r food or hh.. sinfieldaHe's e alse 1I1PpUed several staI.'usti:cal '~cchin~qucsto ~imJ_ ~)lzeliIli.s dll,ta.. "I ha~~e used manymethods to sh ow Ui;vy :fl.i.,ghts~:!ItM.el.' than one 1i1.1.e ~bod." is a.y s I.~cynolidl:s"
R,eYI.lO M.s
lfIl<II s

bCJCs,-tr,1)ckcdi

and

:~Illml)ll~y-

been

'cor r'e spondi ng whh b odil .B e lliIl.l.<I.1m.u,) U 11n d Ed\W<lItd!s,about h~8 ev']~ m:nc c fOf U~:'!Iyfl ~ghts. bllt b~th lfCl1iIM1[11 lU.i!1c,on ~ vi~lc",d. Bcnham,t)u do,c;s!1't j:m;ist: tha:~ ~co]O'gi8t~ allDa~ld:o:l'I! lC'Vyfligh'is just yet Bl~t hc~ like EdI~rd:s,. arg:l.ij;cs ~~aJt rc~caJ!:'che:i'~ !nus~ reaJ~;;::e ~'hatthe!:1C ,c!)urn·d be other" ~qj1I~~Uypl!l,w:sfbWe e'Xpla~~HQn~ for how iJliiI!i IiIlals se~ri(;h; .. Shl1)\V:!il g th at: data <lire wen 3!'CC;O'llultedfor b'Y(lLC vy pro (l ess :is 11011 ughl:" eno ~J'O:HN 1iUlI.:!;

VIllE WERE S.IHIOClKIED !6Y THE IR.AINIDOM S,AMIPlE "BORIN TO Sl~mp?~ f7' Se"h;~m~r. p" 1301.),. 81!J!cl~ :;I! study hltrdi:r dese'I"'!,I'Cs the Ill,)ti()e ofa 'pnmrnier seienee jo,l,u"I:1S11

ed fDrdu~ pf.'lliod olf.l.liUfl'lal'!l!evoluili(lll .. A:rchaeoJo,~sL~ m'gl;lc Ul3!t wijh the ill:vcnil'~()fI1il of speair,,:t:!'ruroweri>. bQ<\:lts 3!lld arrm1l!S;, and PO:iSOll derts, hh;o:lithic hU1IiIting pm'baJbly IrwoIved ]m.crdi!il!,rurro:U1Ild~H![ld!g:~n:te drive$, 8,1!J1!cb 'those IPractii.ced .~ N!I,tiveAlm::rkn(; ~s i1lil1 the 'Wc5l~rm!U~rni1Jcd Staltes aJt the lime: OrBf~r,opem', cm~t:ac:t These ,su:rrouliu:ls,~l1dldrives
ill¥oh'oo all ca.'Ii1l~p l1iHlIl}llH~I:,!;:mel'l.w'QmellJ~ lind oh:ikh:,eIL An ~rn,1?orrnJnIItm][~~rnt d:isti~l.gu~~;he:s, modern IUl!lrml,m1S 11:0111. Ule!li" O species ]siilia.ear'~.l:mI~w:ired'"<Ibi lit)' tolearn awidJe ~1,iill1:y oil socml.ly trarulS]'Illi:m'OO p!<I!btemsof Ulink:il:lg ood aclltng" SlJfdly Sd&~ce\N<lJS pU,'l:lilll"~ ture ~I.ldrm.v:iIlg public <ItJtelltio:n~o a :5ru.ay flm.tr PUIJIo.lfitS·tQ say :'[il:mletlm,ing;

The .Rmld!om.Sample sunnnaeizes ill ":stiUl!)Y"orsex~bllsed dit:1'e~ enees ~n t~l!e albi1Hy of mode.n city dwellers tQ remember t\e ]mm!" tions ofpm1ic:ul<lf' fooo:s at afanaers' ma.rkeL (i~veil1l ithe ®cilill bias in Ame<lJ~UC;@l1l CfUUUl,'C tQ~l1d meel pa.'c:plll.'ation by W'O~'alCIl and HIe,.] ,ooi.IiIS:MmJIJt]()ln by men, sm::.h iJ diffel't:l1ce ~5 mH suuJui Sil~g, buu neither is it i:ndjcllt~'!,fle of"ha;rdJ='w~n,:d" bioklgica~diifiicrelfl.ce:s :IJI1, bmiJ~i&IJiO=

,niJom unive.rsall dilIre~es

bcl.\vee:1:I\'!()llll1en

HImel

Imme]~:Msed 011 ob5e4'!;'11~

tien betweerrwemeu

aud men, Stu]~ ~essC"il,l

SIU(i,h

differences be

~tIYib1i!ted to iall evol:utionOil!i)' past ··,,vliu;elllmlJeIl'ivc.re the, .l:mm:e:rs ~lld !'voillI1U!J,1 ihelillllh erers," While thi,~ ,ge]1);delr-ed divis~olllll (If 11lbor pre'\mi]s (but is !lot: 1IIliVlets..'1l) ~liO!'ig elhriograiphlcilUy ki'iQi!,l~lb~gii~1g gfOii.l p5, s~h iii. p311tim. ,eii;Mm be a.ssum~
i

lions madJe ina sirl.g!te, c;tdlt!lJire. Str!!a:die.s m:ch as this reinl!o[C(.': the A~1Jl~ica[U il1diMtion to eNp!lIm QlIf 'm%'ll cu'lm"dl.y basOOIgcnderod cli.v:i~ sian of ~,aboJ"(c,g".'I,~netl sootp1JlJid (look, ~uell. ee rnathe:l1n'lti,d.ms) in a tlm1l:18'ofbiolqgymtb!i:;t tihfIJlI[liat1llJ!:mS ofSQciam~f[!:ton and di8c.runiIlH'J.1:~Orl..

IELl.ZAI!El'~ .M. BR:UMFlIIEl, MKAE'!JI. m LIE,QNl~RDO, KAlIiH.ERIINEIE.I~OIFlFMANi, I(HIRISliOPHE!R.W. KUZAWA, 1iHiOM IMfIlAI!)E"H REiN B..SJ!:HWARnMlAN\, IRFJBOOCA UUiMAN ..5

D~l»i1I;ilfle~~~.iI!1t1~~pd~~:f.~11!lr'hw~~I.!:'" Yil!~Il'~itYl~"~~t~,!i!.. Pl,6@~03,US:A

IFleSIPO'liil51!ll'
IBRUMlrlEIL HAL (RH'ICIIZ E C iii:!) ~IDEJNI''5 :liumma:ry fRal.ldOlI11J Smn~':lcs" 'j September, p. I) Of,OUiI" research (l}; woe \l\!'e~COl:l1e ~iwe. opPCiflf~nifytorespond,

no

dalla, 'FU's~,sti.!d:r~ $1lO'>V ctl!:heir'llio :;;~'( dii~x:r,,,

ence fir it male spatial

di s,'Cdlminartto'!l. FOl" decades. resea re hc'!:'S ulli1J!Jrf'Orliilil!ed about 0[11: ,e:'II'Oh~t1onary Mstory
UIl1knowil1Jg~y eonstmered sm:mtial t~sks th:$[ :faJ¥Or l1J!!Cll'Si Skru~~~i, U:Isonly when we t~l!:(: seriously men's ~nd wmn.cll 's e!i!lo~ulio]rn~ry lleli~tages that wec:lIJn b:rellk[hl.·lougffil tTI1js: ~ml,dIVleiitent s,e:l{is~m,1:!I.nd e)lpoge, '\:vo~iIf,len'l>

Many s·tud.i.es document

men"!>

!illl:}!!"

[~~m' spafi!!l perfonnance (1). ·\iVe!hllll.d til:mt: 'INOD.Clrl,e""cel.ol] :EII. S;)03Jt~allask m~Hicki:1ilg Ule cogn~t'i,,-e'demiliids ofpli<unt!"lbod ~'fJinerilmg" eve'IThW,in;e:ll, we 'used a me<lS'lu"e that :1LI:oilmUy give's ~en <111.1 amr.ru,lt<Ige. 'ornmf'iel.et a,l. :mg~ gesl dw;t Hlm:ce',Str'dl 'sex: d,i.[ieuc~ i];1, hnnti:lil,g

advantage :~IlD1rn!tOOd s1\iOppmg,'('!Thvironmenl!; (5). Second, co:runte:r

to the sll,')dal~le;)1liIJiFillglilypotJm.esi.s.il1ldlli",i.d[l!ll

dII''er.enoes: ~n s,]![O:PP]I.lg e{,l{p,el~~e::mc:e~ teste pre.telie~m!ces, and 'C 01.1 SruIlIP1]O!l1l1 frequency

m:riqlnc I!l!bffi~~nes.
MJIiJI. M" KRA:S!NOW,,~ D.~INImE1ItU!mW~ :Ii ~0511!i111JA ~ S;U'II'EN JI. e, J6,t1ULIINI! IN~, lIrni¥llf~ity Q! 'iilif'llrni~.5ii1n~ii1 Baflma, (II 9:3:106 .• U51t.. "E1ep,alti!iie;ml 6'f P':S)ldioleg~. \tii!l.e !Jn~"'ersilY. iN~ H\al!;'en. (1 065 liD. USJ\. :J;Dep~:r~l!1e·n.t011 A:1l!~rnI~~9'jt Ul"!i~~'~i\!I ("'l11I)r!1r~, S·~1l!1<!1~rb-,;Ilr~. (A ,~.~
lDepilrlm~ntl1~ P,~ytiooloW,

did u otp:redi,ct spatial perlfhrl1ill1'lIHCe ~11our

stiJJdly~ ,\Knnen ()illtpcrfQml~'!iJIlnen !!::Kll,molling

maybe: small;~lG"~i,e[~ ~ :iml,~un to out for these el'lpea:ilC:l]jccf.lctO[S,,, MOlleol\leJ, bot~] thf.s t~]eary (}flVlther~g-[\eltl!re.d :spatrn.l <ld~~ptMio:ns. SleXeS :S1:1!CP!'J,.W betWr:pcrfQrm~nce O:mJl~j]i\gl.l.c:alorie V!1h:ruti:s :r:deV!mli~ \\lihetheT. 81:a!I:i~tiic~]ly. aacesfood.itcl1iIS. Th~ ]s~Uae ~g~mwre Orill" Ciiio]VW,
ti["~1 "\,{)~lr:;llg11h~red.!1'!,(Jireflmfl~ mG'l, lho., tl'KlY Ci(m]d litJ.e U1Cta~l(;t of stronger:!i~llccH{)!l f{lr cio:p,itiv~mccllan~~m~ s'lilppo;rtimJlg~thCTmg, This sex difkn::lmc(l:ing~thelJ"hi!,g ~sttiniv,en;al ~mong d!escribed hunter"'ga,til~.er,e~ (3), md chim~l'1~oc dait3 gugg.cst '!h~ui:IC:;.;l~l,dii; bac'k to' muIJ;.e,-l~Qmi.n~l {!nQe~'Q~ (4)\ Cj,t:jwg cUltl'l.lral b:iases hl!lbopping and Glooki]lJJg, Brll_m:lF~el et al. pret5eJIJt a ,soci,EI:I~ lcal].l:ing I;Diplani!3!tloillTh:rnii our :ros~~lts, hek ~I!te~ T 0:.11' h" ClQIl~I'adi,cled by othe:1" :studi!es mld oun."
mCd.l<llli§mifor eM'Cle1Jlt ~"b.eiiiIug, nat one

93:1'(l<.6, USA.

..
~

~ ~ ~
~

identity. The sexes dim:r. M e~ l'I;e'!,lcre;y..· l t~te olt1"spdTig, o~ ,!bv'c:r~,g.c fJmi~yarc 1;!!Irger, le$i~ !!tr~i c~l@t;c. shorter lived\,ailld 'bctteF a,t mc~t'<1il r,o~atiolf;!If!~k~ {2., 6). Dcnyilill,g these .and o~!~erdifwrences will net :mali:!;:tbem di!i~ppca:l". B,u[ the SciCill,ce thate::o:plore5' these mifferell,ces pmll!idcs too:~sN) camba.t

:i.Oci."I1I:~y .~emnooi~ 110mtm:1.~ 6lWilun~OOl'Ih\. Fi!t'l<'lU:y, oilly thofle; \l!.'ho,illSi.8t UfOl1 cgalh:aIri~!l]sm dc:pc!ui O~ ,e~ait~~!!! biolo~ile,d of

IReIf~rmc:es
r, ]1. ~~W, .~\ M. t:;ri!~!Jo'iN.~". TH!!:I<!WJ :5,1, (, 'G~l:Ili[). P!'O(. !\IJ~. m. 2~~"~~19' (~(I;l)lt l,. 11 t Iffillipi!!t1'Ii ~l' f1P{fffl}m;e!> m [~fl'i~~ AbiUt~ (l<l'lJ.lj~il'O~ j;~lrurujill,M1!h~h. Nl 'i!!~. j:. ::lo!l{J~, 3. IF,. ~', iW:i~lm'll!.:fIfD!A~rlmli'pa1 •. lil4. ~ t~DO~J. !l., C. S. Slillitilro. ~iI1IM~m-llflii'ilg Ol/,d I:iilmlDJll ..Dl~li,r:m., C. 8;, SI';lIIr~ml. III"r. Elwu'l', Eds., ~n~rQrd,lJllliv,. ,Pf.el1s", o.~rordl. ,:l:l)O1'l"IPP. 1l2-'140 ... 5, U. ~tJg~. f. !iir!C:ip, EIJ~ •.fl~hffio; :3:;!, ,'31 ti!oo(tl, 6" U •.I!)~ly. ,M.J!'!!~~orl,~~ ~L!'a!ji'ion gntf &.Iwl·~Qir (F1!,is, Ildnflill:'O\. I!!d, 2'. 1518;1).

IlETIERS

TheABC:s olf: Muniiple B,ondhl0

IliNI Pi IRIE(HIJT IPERSIPECTIIVE

'CQmibilrl.EIII'iO!W1 of nm

EH fragrlremJis, i[l t~'1.ellJ:slt

excited state~Jfa.at leOOls lothe slDdaOO!l.lewis.

type: Srt1lJ.ctuu:w~th a line'ilTtJlTifI:lmgeme-H:t ~I]ra-EI~" because eilchfrn£ilnen~ .liias tirurce unp.8J~lrecl e:lreoons tbat y~eld abip!e bOlitd, In 'C:OImlr8ist,. the ~nle~m::;tio~.l:S be~;l:1!'-eenlil-ll fb'I:8," me::JII:ts :iliil. the .gaio~liJ]d
!it11ite

(,6 AP'RIL. P: 6:U disc'~lSlS]ng hi,~h bond arden;, in metal-metal bondil1i~and [Ill the iii licon homola,g ofacetyrene ]-[~Cri. w]~!ere, e = Si, F. Weinhol.d a.11ld C ,R. Lll1lidi!'l st1Ire thai '''itlmlefi.rs:t stah]c Si~g:ii
g.eoJII:l.ctry," IC]tU~,lg tirue

·.",Ellidl:I11~S one

,ehcoonp:air,. otle' enw-ty olloitill,1JilId o~ one tll'qlarired elec;1Jj0ij,-r:::11'!:phuri the preferenoe-mr

A mmdB, over C. A.cetyleJ~~ d~JfeiIfNi-om its
h~11V:i~.r Q~]og~. heesuse ht1i_1ki~!n-ujch .IC8~, h le~~e!'£)' to el'!:cite CHrro:m~le £JQ1.IJ:!id ~i,l~tg

thl)o~:et:iC'a.]t~nd.i]lligs for lrJ:ci~eicu]cs 'I:hat l~WI"e l1'igh bond OIMe!:S between _e~1I1s dead)' showslillillitthe ibondingin t~~.esero11!1]JOIf~dsis not p~\oJP'er~:)lclesc."libcd by !ciD'npleLewi!i~type str~otures,. IFUIlU'~' 'WOTrk.sbonM usc: met.1ruods: and ide·t1!)h<l:t are not oonfinedto ,c]ii1lss[c:1Iil. t bo:lildil~g models,
GER!~UJT F1R.~ll:(nilG, ANDi IULF TtONNIEIR.
f,~dnber.eiitl'

speJ(;~e:swa.sreported to Oldopt 11 plamn, bu~

i,~an~ilne<lr.tr'lIm;;-beJ!!lit

Chellllie. PI1~liW5.ilJil1'l'l~er$il~~ M<lrb~~g, ~.m~G~rllMl1i~.

rl!ieel"i'if!il1l·~~r,g !,. n.35IM,31M1iIJ.burg_.m

wmk. by Se'kig~tdhiet ,,1. (.l tThey show r:it.nlOttJ..ro C (J'ig,. '~.) fer me patc1m!t compo'T!!:!lid
HSiSiHflild

the ~xcitedsta!te

mrnl (urthe

hcavie:r sp.ecics

IHi!:'fi!:iftli'i":4!§ :;L. l\5:e!k,iglild1l, It ~rnjo.. 1IlI.. llch'lnollv!!,5.dtJ'lC~j;~.5., liS" 2.. 01. 4. 5. 6"

cKpl;lin it!li!,r;:: diffCr,encc to '~i1e bOlJdillThg sitmltioo ]11 LiflCo'l!f' i'!CJcryl~le iHCOH

te~'n.~, :fhigh pref(;~(': f~r ,.otb~tal charo ~dc:ri:IiJJ the Si-Si G bomd (2), U(lwcver.~;!:tc C1()1l1Jt:louud~,cISilSiH ",'.':IS:,':I~I·,ea~ :s:y.~~thesi.zcd
'~!

~, 199~(3}1 15 ~I:S ~Ili!icrtlmn Swguchi~ (1J•• whi)i!i!O:~!Itedthe s;nbsll:itill~edderivati.",'e RSi5ilt 18

/\

,~I

,
.H
6-1

S~-Si"""-

Si=Si

IMI

flH. Ol'l~yill'~:he cal'boil:lcoil!tllP'01!.!l1id do(':sthc stirOllig.e:rbonding~n. Ulcline;irffi'OITn HC=CH ,co~llp~nsat(; for the ~dtat~onen~rgy (If theihagln~lllts, The e,;:pedmental (l) ~nd tieore'r:ical (6), ~hldies:dl) 'Im.ota~re<e wi.th ~hecC)ne~usi~n of WemhoM ,mll(~ hndis; 'Illa~~[I']ntu~ symhetic " lIndi I]lomp1l~J:<lHou<!l[ exp.lor<lItiom;s11iOlI~d be; guided. by closer <Itil:'e-~tiouto the .ax.i],illim~,]y rnslcbed doa.laf"iElccep:ror ,ilmil:en.ct~QIIstilal Lead to £'wQmb]e:[.ewi:s4ype bm.ldiing patterns,"
Careful
ex<l!lrn~ll,1Iitio~

c. R.IL3i1di~ f.'lM!inhahi, I~ ~ m. foe. ,U 8, 1j~5 aOi1!Q~, g..Bog~)', 1·11. I(J~1iifl,( iil!!I'!I!I1fIt~ l·L !ll!!'1.lClfllli:o!!S, .I'l\i~. I E ~v.. ~.~ "IU 1(1I:!l?1}. HI.. Li~~hk-aJ~ IKijh'l~r; J. .!1m. (km. ~, 1'(1:5, is MiS il900). Q, O!rd~~!!iet~ ~, .Bag,~~C. [)e",~~k;. J."L.l)ii!!.tDmb~~, }. diem. flfl~, 9l1', ,~@Il U99,lI, ~,ILeil!, A. 1()r~,(l~.G. l'er'!kfing.J..Am., C:fle,m" .:)w,127', r

com·o.

"6.

~~ot2oos1.

R.Gtsponse
lHE Sl1RUaIUIRAlllS:OMl~RS AT ISSlln: (OINTAIIN S]~ S~. ()~ds with ei.ther Q(I1;ebridging 11 ,(Cs b POiNlt !!P·()IIJ,psY.Me~.y I,. twobr,u dgi:lilig ll:'s

ofdlC e:"'l.f)c:rime]]ilttl,~ ;fUnd

~i!1l.1. ,El1lerg,~tic;lI~ly IQ'~esllying :strucll!i r'~s D, anI:! A. C of IHSiSiH .. Ue ~i'i!l!S il~dic;ate m:nl~ tlileatooi11k COil" !iI~ctMt~e~ b lit ['It)t 'tlil~ ~l~tll1)li!. paitS D'~'Leili1!JS5UU(-

lures. R,I!~alwQ'QiV!~rg;i~s kc;i3Vmol.,~ro '!'liOm, (6)'. in

\vilel)C R .~ a b1!illky sily] grollp ,(.I). Oestambes

-~~I - "'-iii' - rl"-':ffi 'I.~ tl;h - Iti!ll 't-b.'l __ J':: ..,qL_~ ~ all!!.! 0 ... !.IO_.!W_~ 1:1) ~ __m-~~~.;!II!.!l:i! .. 'til'" ": --~iJ~i'lb-

g;eam~uy {If HS~StH: does nct ferm struC'!:lii:f(lC. but !fidh~]th e d<mbly !bridged :l;tr1i,!Lch.re A (Fug.1 ) prov.io!':!~:l.y pmda;crodby . abirtir[o,·ca!c-~laH('!ns (in,. '1'I(!~I;Jexciu~t~OIiiiI A. of yid~s ;aJ~lother ~80~ner ~ll!SIS'i HtidC:l1Itil1ed a~ stn~c'l'l![re8 I(Fig" 1) (_:5l Q'~lIn'l'i)[m cim.clllic~~ C:!Ilk:~llaHons, pred:ict that :stro.clnl:es A and .B !U"elo\ljIerin e~ergy~harn structure C {,6). Thus, the si~:icJi)1lhmnril.O:g,'Clfa.cel)lwlle dO(!ll ~;lotexillibi,tme Lewis-like bOl'ldullg 1111!ttern disClISSied.byWei~lhold !Ifldlanclis.\,\i\liio cmls~er Cllll~Y eJleJ·.gi.!tica'l~y h[gJm,=.10ng furm C Tl~e fire mln~rellitgeOl1llietliy oJ"t~m RSiuSiR.cm.upotlu ofSeldg,ll,u:hi ,etal, (,I) OOJlle'S from st:edCR:Pl]~ mOli1i1 between the Dl]]ky ,.Rgn)l~!ps"wJtUcb p[\~ Ve:Jillthe tOrn:Jim:ioll o.ft~~eiOO'm'l:ricr(ffmS A and
nUlll

NM:!l focm;: '·G~~l1iingl·lli1:~lJl~~mn9~ by 8. lE!·_,.t~rt5 O~l!OOer, " .. 36). Tn!!: ,31r:tal~1!<S 1 'I'l~Hl~ Jl.GIiJI annual oolir~~retl{~, Hmn ~1II00 ~m P" g:~ .~ 6 .~mIDh,~ESA. rnr!!'ll!nH!' On! p";gi~37 \';'@rl!' !1Ij)Il~ by l;(il!jn~Jii(~~lu'!i "nd l3.ord!!H:50011 IIi! ,1J::!IiJrllmgE! w I!JniNlilr~i1y, nlJ~03vid5roit TiI~~bl'tro,i!t of their jJ05hlt wa~ !lubli ~~d ~n<,[,,~ 1lol'j~..AGUFdIM~f. SrIPpi" 34 (2®Ol}. /!iliO' the cred~t ~gf the b(!~m 1!'1!'1 on p.3S sho~l\jJ~d ~ge ~N($J!, ACCE'5S I[M~i'!a~,. "fll/WUT c.oi!lsumll!!lI ULCAI~chitectl.!~e ,~l'Id Inn.Il!Jd~i'I!~~ TI!dln:DIDg~ O~;g Ill"~ CQ'IlI!'rCapti(lom, (28, Septel)) be~ II. 1321)" 11111 [redilllifl~, !lie AIldr'il'a Ottesen"'$ I'I!iIm~was rni:!-'!!pe'lq~lii.

Edi1~\~I: "f'l\a,yingC:1~mate'(hange ~er"

i'o.!! iJt 2"C-'wil~

!bye (I'!'~lleil!{ZOJ!Ily;p. 2 9S1Tn~pmr.il~ inten~!!I ~ red:~[ea .... ra!ile [I~b.al Wil!rme

fi!neitilltID :~lgriif¥tl1d.la\i!i!iril9!!!gIDbaL\'tamli~g 'be'l[rnit~d10 ,2"(, I!lMJUlillt U:le< {Urri!illll~:1I'er:l!9I!' redOll!iII b12"C. b!!

COIMMElNir IN"AVesltige Q

!ill,"

lEar1:hi"sOllde:sl Olphil(lIIIHe"

AU.eR! II: Ilmlirtmari aoo CllllrlC: R., IL Fnilf!ind

~um~~i!lt {R)~rl$, 23M""r!:liJ 2001, p. 17M} r'lf!\PI)r!QdI :t~ fdl)n!ifiuCi!lHon iof·i!ln ophiolite ~ul!n~~ wt1!hilillll~ -3J3c rn~~onry'ta!r..ottl ~cUa,slllPfilausta~ ~~t Hgml!r,~Mr'did 1'1l1t. e<II:Jn~locI~illmUbil Ioo:rt mnlaiM ~upra,(ruMill ",,(k~an.d ~Ih: dlkfs ·of dii(itNoMt~ge:s,In~r d~ th'!r~demQ!ilI~lr~ 'ih:ai: !he ~o,pGsedl~o:!'lllllOn~lS, or!ll~ 'ophia!iite are: coM. FuU telJiJt allMWf.wei1!cem!!:9Ig'~W'comerin/r\!lIIllar5a.:511'746(

ca.1ly mor:e smble tbruw lilSi,SiiH, whi:c+1 Cmll olilly be· isolated i[l alJ)1i.~a'~emllilpe~lIture pl;~lm (3. tJU!t ~his RlfIU;!;1S ootrwrn !:110m fil.varaMe S1-5i lJifldi~; Wgror-a.cdofl~blt ra:dlcr 10m the sl;S;:ric

B. Se;ki,b,lillCili'S oampm~ndiRSiSi R ischemi.

COMMElir OIN"AVestiige wan,en IB" Hamiiil~oJII

cd IE,ar1li1i's 'Dllde!S'II[]IIPhiiID,llli'te~

,"1.

Th~,claim lwiF~rne~et (11. I[R~~Il!i..23M~1dl! 2007.!p, 17Q!l} lli~~ Grel'Ol9nd !IfI:~t~~l'Iit; 1110& mq~~ ~aI~OOJrdI!!'!n:l@!!IF Rooi:' sprgaoingls ililmnnpatil~'~ withl ~I\.eir ,OWl'lldata. Thi~ !lurp(for~J1!,dl5Ihil!@~OOI : dikes, 111_ Ithil!!'oolflflpOsi1:iOI'lI r 'P')'ffi:ll@nitic o IbJ;matl!l,~allld c"lid! Rot ~ W the adjiKlllM r~fOiIooes!'tic pillow 11a1Ias. e~~h~lyJ!H1 ~ ,ophiolitic analog~ altdi boaih are N ~~!li'e~!~Ik,

~1J1l~~~~t~·H.sri~(~maj}(!i'W@iilmn~Qm.T)'I'l!Ilil!'3l8f58i5lrltl6d

jjrotccl:'ion O:fd1C siQ~(!Ol1.atoms. Wh)t do,the et!~,eticIlJ!ly lO'!l1l.i;;"St ~ying stru!D-

RESPOINSE OOMM ENl:S In" A,Ves,~ige of I.anih's 101 est Op,hilOI ~te" m d
Hi!~aitd F'i.!me $; M!:!anJ@1'!
l

rures of ~e giliotm hgmot~ '01' i.icC'ty[e~e

exhibit tiliie M:1liU-"'tlal hydrQ.gen,·~rkl)ged g>eQ~CQ:i~~ A andB (Fig, I)?' We '~~. IMl§}ly",:cd tl~e i1liille:mcliol'ls oot'l"ec.Jl l'lo't.'O E IJIfragll1.tuts (\,,1}C:1iC H"" C, S;~.oe, Sm., .Fib lin ~!ee~wmmc N01Hlld , ~aJ)e IDld cl~.efii~'St e:x:chedi Siial~,r 0),. h 'is mill' tlle

it Wi'. HI!!!~@!fIUS,ta!lmdifi:ll:tj Mhf!~tRo.s~I!!:g(\ liCal~Uls .gle:h~e'ri!baidlis M

.DJJ:mmiflll~iby NI!I~lTii.lni!nd Fmim[J, f(lul H<Im~lon',qu~li!lnl '!Jill ~dkm~~ fljjf '~IOO pr~(1] ort~;!! tsu~ ~ki~itt.lfheir aib.iraI. WnaiF~aITe' parliclil'liMIy eai~e.lerlal th~~l<iIi:ity o!OIiF ~i1if~nr,ed:lihe:e~·<Il ke 'OOilllrP~, Ibe cO;Qenili:(ly ('d pilUJw Ia'li~ .am.d d!i~es.. O!ll!dlhe ~O!i!e;{~l.eme~!1Mdw'!i! 1!1!i!;!l\V!lllent'S. 1HI!!~e.we e;~p.md:,on our !!!:ilkma~'ons in re',lpon~e~!l,eadli of t~rc!!!m' ' lfIOO~tsm I:I1!'Hlf!ri~5HiiyiJtr 'nglfjllll@l'Ii;!;cfln{lilft1Bllpro:l<ltiGn,

Full t@io!ll.al ~J6Mmm1Bg.Ufgtqifoon~QIil'llfIllW31S15aSlr7!'l6~.

2 NOVEMBE~~:2007

IlETIERS
(C2v :P(}~m:gficmp s~metry)'. or no bl'idgiIl£: IJ1> (trn~,l:s·l:ent. C2TIiIpoillltgnJl:lp ~mnl.et'Y). <Ill ofwmch are ]ocal m~lli~lI<l" The"sec a!]te:mll~ tUv,e :sh:m:rl'l.uJe!>\\lCi!e- Uli.dy m.14:edin Seki\guch~

eJ a t..'5 ,ori,~~1l1ll1Sci ell!C!i?ReiPorl of time first Si""Siltbp.Je~ond(n" ate .:'IiCOO:ilJl,r:mll::rmg ,Pers~ec'liVie{2}" and in 'Oll.lil' OWllrtlcenit :R.eSic<lrl::h Artid~ (j).I-~owmiew, in the ejOilreJd ,of ~lI.lf Per:.liP~tiii{c ,(6 April, p, 6~)1 :ij1jqdlH':b!'idg,Qd i8omer~, ~f,e~m!~'t;;tnt~ Th(:;y do not: o~nhtiul SigSi t1!.ipJ.~ boods. NiilitlJ~a~bond. OIr:bi'ud (N.BO)aJnd flflh!:faJ~rCS()lla;!:voe thei.llry (NRT) analysis (lIf~},e~l~brid!lled [SQmer:;; y[cld~, ilcadmg Le~'I!~~, sooct~s \'\.~thSi,-Si :li]~glc-banJdoog In thee2v ~S!i.)lllcrarld double-b~'l1id[ng in

the Cs isemer (add itional sl.~:8iredclien:si:ty ~~;l snCMIsub:st~tm::llIls, disfavor bri.dgU,Il:g; Ilmdles t~.lalooce·s:Si!lrily lower the m<lJxrumlIM a.ch]eN~ Si".H~Si. :~nl:cr,lIcliQns: .!il]ves net S]~S;i NRT bond arders of l.811nd 2.5,re-spectivc~y). in lll,le, bone] ,rn1:l.cr. A'tJ, strJiletlill QUit .Perspective, tbe ~.lighest i1.chievi:ibJ:e !Jond ,oruers mOMlike;ly cmUr.ast to the trip:~c: bonding (NIH bond will berea]:i~ed by '~intl}mctiCl~I~ th~t .Iead 110 '1llideF of ,2.9) in the eited C2hisoJmmier (4l fu[~C'rdiscussi,o~10fthCl:;.~Ii,lt'em~tiw ]~K\llili6rs: fWfiOI·~bl.reLev.:'i!:l";ty~c bOilil;d~ng ~i!liUem:~;"a~ cle'I]".~ydeIllillIOJ.l:stril,wd :iu tJruet1in,eoreticrn] klig;ic and the 'jlJ],tei!estillg e~,ectronic origins: ,ofthe that ~edllDsuocessfu] p'redicllirClIl (5, 6) of the pt'efe'ii'e'i!liee:ror ~I':bridg,oo veniu!) lIJllbtid:ged bOr!di.ngmQtifio,,\;'ai~ pr'ec'l~ld~d by c()il1!!5,idCrn'~ Cr-Cr qu~~)rt:u.pi~-bo!l1id~!lg lNwM priQr to .~~~
tion s of] e~glhf!!]d rel.c\ia:r!c~IQ ~]nC: maj~ n::~r;;:Iil!t s)'m:~~i~ (7).
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I'!iiadiwn" H.lHlIUnhl\~l\l,ity-I('I'~C1Il1e., Madli~QIii. WU SiH06, ma:fliy bomd:>ican USA,£·lTIiH: landr~@t iii em,1'!Ii;5 •• ri1,dlii (C.~.U~ weir;! ~Dld@ be m~dc Ibcr\vcc:nTh a!t'O!l1ls?'" f,or silicon, two ~hem,vmc,edll (F;'WJ Se!kigIH~h~'$ n~cmroopio·l~cS!l(: ~Ilthesi!!i ~Ild c ry SUtll.ogra.phic ch a:i3C~eT lz at:~on of til C: IF,Ii~fi!iI'@nt@!Oi'lnlill N',0,ti!:!O persistent .RSiSiR {ll=CI~(Sillv1el~~" !ru:g~ flf.St :1. A ~kjj~li(ihi. It I'ii fIIjp, 1II.i.II(hlnoIIIleSr:itrurl! 3;0\5,. liS,S g.estcd t1~3!t the em:wer was: three. Conl~~].-, (201ll.0. 2. !lWell, .lldf,ocd05. iiJ'2:<l· ~2'OO4). lati:O'l'l:8im an:;dys:is of ~1'Is:.lbent Si2,~ IJ• \!'11:iruic~il C.1lI,ILi!!Icli'~F. 1l'r'ei~lroi,d" J. m', (hem. 128" 1,n'5 bears s,tronggeonu::tri.,e mm eleclTI:}n~c s;im~jilur~ 3.. t!O(l6~. i,~~o Sekilm;hi,'s cmnpom.l~ s~,pporb; tlili.:S, <!., Wt'!f!D1l~~1i!t·Iln~~· R!lbcl'!d 'or'~~r;$!ilre.ML\Ib'~MiSl~m N ~tl~ th :S~Sj I~~!~!! p;iir ~h~,~ ~I!~e ~~en~d by e fO:rnliuhltiQn. Ongo:ing, synthetic :~tiIJ,dliJese t Ilne'Ff,~n!]mgg~~ lit L'e1ifl, ~ Kir~pp, g. fr!!IIlKil\;~ c;qll;on: the lmppe:riIIlI~ts ofbQmH~lllbetween l J AiR Ci!l'tJi?" $«, i2~~. ~2!l1[li5). 15·.2-90 two o1iilonrs li.keilywiU fetl!tm:,e b!!lliky .R sub!t IF,. W;~ql'lll!!lll1 (.I~.nJ:!mil'l~" IVil:I!ellrYmld,lIoiildfh.'.A.fflI!lM'!l'l BuM! &!\I.M! £rol'll!lll'oMtl?j:lr.ot ~pr2,di\~ {Ci!mbrlifl;1'~ stime~1.~sl'ilther dmn [I fOll" twO very difrere~n tli'i'~\I.f'l~~~(~i1~~., PfL S:~~.!'J!;9', ;!OM)" reaseas.Pirst, ~1'a.e l~~c; pmtectiolIil,p[I(J,!,fided s 6.. IF,~v'~rlf'lIWlld,C IR. ~afilCi~,CI,It!'m. ld!~. Rt!!.'.PtCf;[:lf(€ by OOilkyO'lmd.ooe~.lts ~litlders iJlternaite reaef~e~, iH (:l;(iOU. 7" l ~!J11j'e1l19' d.•. ,u'J](e 3:1.0. M4 120QS), S lion pll!thw<w~al1d eases ~S(lhlil:ioli1.Second,

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Int he' (hdf of Me:.dco, tl!1iC rel.atrcd Gulfmenhade:lili lBrei),()Ol"tia extetrsi vet~shery, :;t~:l.1:SIIJIP]Xll'ilS mill that I:I~ml~ l]rue AJIEJnt"ic- co~ Sf by one
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Tales lof a Smlallll" IB,ut Cruci:all, IF'iish

'.1: fi:rlJt Sight,. TIJf!MtJ.Sr lmpm't.~.rmFish •. ill the Sea IIp;pit:a:rsto be-] O]ll~tO~],l:@jt liliie~!i!.ewlilliidt earlier pve us 1lIC:~ ClaUI1Uof cod [rlle fish '~hm dl:iiliny.ed.thc\~d

genetllriiOlg oantl]cfs

lm:ul lhose or f\'\liO deca~s,

O!lrlFec~he 'u,pell ;Pllrt oithe foocli\:vcbs. n~ireat~ t

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(1)]1. Ame:ric<)]1, 1l1'u'1Id I[the fOiJJJiildingfish (,J)]" and P~l1lgiUnill!:ltQotb!fhihj' ~lSiO k~l;oWJ!il":-J Chn~~n seebess [the; pe;rf(;"Ctn~h(3n. These
all. ~mp(llrt~nt bCC~t~Sie of thdr iiii1'llpa.J:ts. (!St Of prc~i1t. 01'1 poorp[e: '9. wc:ts .. But p Atl,a!1ticmC:!1Ihadell aj.,.'e~!Oo~·U~ tYl''i.'U,IIJUN)ig fis~in wete

Mmhmom.cdil]O'W.,g Conflic:t hind 'Ilways :-l~nmlemill between th~

PI!~l1t:'i,wh~!l:lIOO·jf .111 t:it:l1Le tili1Je (:JOlIst.

1,1,1til.U;: 1iIIiJJealJltime', e,c:olagJists diis;c:o'llen::(i]i th!J:tlnel1~,mde'lI, J!;m:ven tl:ieir feo(kn!il; hl.iLb~tli:. "i\Ioj~lI'el:iiJl.f'illil1i!il: aJnmliler c<oolqs;ic1l.] mh::: kee',pg,ng1:l]~~,blooms rn, check. Altl:icrugh t~~e ['(de

of oy::!t~s,ijIiJj ,cl~ll['rifll,g

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re~]1y i(fiufl"emntlmllilliJ.cod, I>l~;!:!d,.~ldtoOlhl·i&liI!

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91l1Se

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n~:aJt\:ve do no~: eil1t and

~:b~\:~>' new:r will,liba:the't .iil: 'us Icat~n by ~lin.{: t1s.hes we UIm: to ca.tch .wnd eal~ T~l~US~ tbeeoa-

a:rrrud 3.1DUBld thi5 :fis~1.1l!l'e rnfli"el'enl q)l'ruft.kltS. ~bollJt others, 'W']~JtIl'ei:fI\el!"~ d ent jpeo;ph: {dlili: French 'I;c'eI'sIlS~le H:lgl:isilinl.il~,e li~il(l fishers 'll'e1'$lUS the enes using trawls,etc.)
OOOlMlt

t~~ds

fmmil.the

c-lOln.:p;ereH:lfbil" access tow·Jrno]eso.mc,

W!jh 1J1;leJ,l&,OeU,-;,llli oii,ly. bmlilY. sr.l1lB~I.ffiiIId F'Cjputudlliy illl..trIstlngllepfC:i>enl:tIitiv.e oftbe fu;eJf~

food, fislili.

T"iI'UlM 1!!1'! 1!I.i'!I1m1tH"MOJliil>~~.U;~~ mlli!!J""'rn.~.1"'''-~--1 I

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contlictf> have bee,llIa:boottlm.e uses" Idli~:ecl Qfind:irect, to \\lhi,c;l:!thi:s fish was to beput Tmdill(u13J l,y,menhaden W1I'8 tied as

nil,! fiJ_~y-lhc

fc:mlizcr, and &e oook.m;s aniflim:reMillS

tiO\i!iO!i ~O\V olfigi~

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ea.'l:eilbY:ilI liiigti f~sh)~ iir'id ike rnlludtoofi~h· ~. ('\1i.'hich c!TIpIIQ)'cd :'!pot~-rpl"f!!es i!l!OOpu~ ~ei:ne~ h".l'save 'li;lc!lJlf!'Qm f!!J!c~()rud dooHl.) •. Tlme d~bate hll~!lS~nedil1i theI970tl~wJ~ell it Nf!rr,f!g~n$,'CUs. O~ the: otlmef was ] oim::d by recreational ~l~lld,the I.arger fish cxpk)~~ed <Wllglou, ,\vhOi:lie :mrge1~rccic5 Th,e Most Imp'CilraaiM Ash by the learly E:tul:,ope!l~l :se'i'l:kn (e:lpeeially sai.ped bass) iU~i!!Seiil depend!;)d onmenTht1J!denalong lhe US. Ea~t COa:sf•. smdl MI1Hlh adJ,en i3il'ld Am 'e[ Ie a ~le :mam:nem,uTIlna'!s also :3!bu:11Iide:sp:it~i ,ll!sse;rlIi(lll'ls 1.'0 the 'COl'n:by H B(!jt:fi FrsnfdlrJ' dant aiong that sasne coast, tmlY by s;!XlIk.espe:r",ollJ~ ,f:SO!n1J.l(!? t s:! 811d P'm:ss,. W.3isll illHWI'I, all fed on mC([Ihadelrn, TI1iis fiS~ll, elected offfici.aill~) ofthcl.'mtlo. D'C, 20[17, 21,B PIP. $25, tim} fishery, bouoees back ..if~'I,i\ellihe, ,e~:mIU:e.l'heroile o:f and the mieroseouie E1~ga!e it l SBN '91B1 !m126;] 141. feeds an ,fO[]ilH:d th~ I;lilll se Tlrisfisheries o(ulll[c'tt was me'~lllidel1i iu ooastal.eQosys~ew.sis IIl.CM1\!!!'e1l one oft.iID.:fiI:St:tlmttp:~tt~d those ullldle~l'Stoocl. m1<1king :s:rn\Mi,e.spec:iesrnrg).lments and 11.lInOOrsl:ory. r1Sp~tr..le1Y.of l.UOst CQrust .. lfeod \wbs,mm NewlEliIg]aIld~o j,1iI:tm:smd.i:ll1 .81sWl.lgJ.,e~SJ~d.es ..,pproi<lC~l, h]th~ ulmpossilD~e 10 1U<I~niau[l, Alild ttae sele.eerpeeeF.iorida <lnd l)iJjrti;Cl:Jlm~y in (i!CS!lIpeakle BillY. erte dnlililiml1lil:t, 3:gflj]IlSl 'ldJvm;o.(I't~i'li1 of what is l~on tll~t still t~shil:-s A d<llllt~il::; muenlil'f1denfQr manWitml tlru~ ] 1l\f e:ntl(nil, ft1sh meal. and i~:::; EiQW cOI.IIed "ie:cpo!lyste.m,,111lsedf:ishe:ry o lied:IlaiCituon dots, not h(\J)ven lmo:n!!)l:'lo~yi]iJJ s~puse fOJ;':~cediIlg dJi.cke'J:lI ndlivceteek, the a ag;e:nre:nC (4). Theaf6~Ime[l't~ [IIfbotli\!sides aJre p~)!'ing Jis~,.eal.lIif!df]sh oiil to the M!lrkc:t. iud!ijistJr'inJ fishery for m.e~l~:tId.e]ilincrc~sed sri]] with US" even tho'll,gh fpl)edict21ibl:y) the lndeed. it appearste be "Jbleto mll]utain ~ts tl)eJN!liC~.loomll,y. ,especiillly 11fler WorM, W.aJr 1.1. Mooted. rm')!q:ctiOirl f shiery, .i'l:~orlgwiltil the ~~:~n· fleet oI1lii.ybec[U!I;SC oftheweJfllre (s.ubsi,diclii) it MC·!lh~d~tl.w~~iell <l!nic:rhiil!dfom:t~ m~m~1TiI~ gile ~t()(:ks: OlfD,l!,'hiiCh it dC,e!l(ied, ~.flfglO~y colc ~1.s. Pcrha,s. 'ilUr.s Sb:l!~ wi U have ~ posinve scl~!ooWs,imml!~J(lto tI~n',cl!!~icd :h;il)~des ef 10000psed. AUlha,t ~s!cft~n tihe Mid-At~3:nUc clmding;; H. B·l'l!QJec Ur!kli~ s~as:c;ina:tilmig 1.1(';F prodi'lt()ryfishc:s stl~oul!ildling(heWll, became ~gj()il'! is 1.1, ~mangtodl:'O'fm~rih!('lck;n.lmtl)ddlins: eou~Uma~es '!.IS fQrn-'aioo to th.l1!t kldk ill Cil~PC~~t,; Bayalld a ~;ii:'ig_k:f~~thc hIt· sleamc. Theckrcdiu:cc>di "lUMbers bc:gm:'i!to IR'ili@ftMe.s; ter ~ di:stiiUa.te of everything ~l'a!tcan br;: VitrOng :1. U. t1w!r~II't!lKy" (tJ.d:l.fJJ09Il1#lJfrl/rJ~mll rhmcn~ru ,~ti'~~d!""'I:rh~ fi"h c_ .~~.- (·il:ii ·i'iI·'r~:k"·liar: ........_ ."" "ri, __ L I!i!"""._ L _._. c." 1''' -[,,'l"--~r!"~'!- 10I!'" f~ WM,,J M&IJlJ~, N~~ li'orlr. 1l'.9,)?)' Th!l'r~i!!~,~' i~ Uilef~herl!;!s·(e!'!lt~, FtquaUcEc!~)s,t~ ~t M(PI~i!., 'r~ fDiilltJfn~ FM m_ffAf', S.t~Ili~.•~MI GlrililU.. but wen-CQfI1iInectect cO!rp{)r.f!te O\V!J.er:;;).,. 2.• ]1,. ~1eal~clllJ"a:bi!)r"to·I)!'" ,22012 M.ailm Mal~ Un~verli[ty O'~Briliishi Ni!'I\ni'mrlo:,.2il102). Fm:theroonh, olt1:''New ~'~rseyalndbeyond, 1ihe 3. ~_KJn!!tfitit, ~'ltQket1~.Pi{l]JM!!,. IlMtmng. dilt.! H:i'l! iWf~~' (1I1~l!Ilili>l·.\t.ln(l!!jflii!r,IlLV~lim, Clfilj~Ailil_ ·li'IlIillt: E Ilpml@ n~h'~ m08~ (::Q!'!lP,O!) 1!me, ~ .11.i.!(:I'm.~wlJ((NWH(g. wldc:l~ mCf~115"that W11ich 1:iIl~llIliU.1l'eS" t~e A[g:(lllqui~l :1~Ii£J!M!ge of Ill\: Ill. @f
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nsl'ieiS exploi:ting ~lI~rf]~h.w~lIO "Il"":iHlJ!ted. ... ,_.-:.,-4 . 'I" .~£u.'fi·I-I~.·,']--o'-r'l]- liI!,,,.'l! _.. ~c ("1I~O!!.ll«.. . -11i··r--I-r.".~ 0" -, 'I!.~ ~W._._._ij "~_Cl

"e]ated m;tejr-fe~deli1;wa,g not, NO'I'I'. pe()p~e realize '~hi'lltit 'ii,'i.i()1.dd be~fi!:'id:y 'to have Irltg~ SiOhoo~Si.of mmlladc:n iilel:ij;lS~s giarl'!'li \'<],Cuti'imi1J; c~ea1lWrnitI. 'Cl~~~r!JIci!k~' ~!!dI~;u~l~rQoa~tal Bay' bodies ¢!JjITe!iiJlly cho~cd 'by <'!ilg~t1 bk,~_u tri.ggel1L':d by furm :l!U1Iii~i1"s, The j\llo:H imrX_Wfa.U,' R~l~ tu lh'f: ;se!l~whic'h tells ~ndllmm1l\gh:~ydm:'lUIi1iH:~llt$ t!lm:esc gtmi(lS) c!Juld beseeu $~ yet mother Fie]ples;f; cornIne;flt~ry on n~!e ,,,lay""!!;; ~~et:rras~,il1ig' ~U!r il)c'CmllJJis, 1HJl![t it is ~n !Jpt~mist!lcbook, ]1 de,mJ[s willi ,1 :resiUenf little' thing tha~, mllilile ml:gc:r, [ollger~lj'll'ed species such as cod. lifHldJily

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pmgram Wlinc:di widesplJ(~a:dl eirenlation ..W~th its pe:>dIign~t:: of"'Ro:~ H(:MlaJldPresemL<;" ,and] <IIC;:1!stof 8 oflhe' 12 Cls:~u.mts wholu,ded Oilll, andtwn others who c~rc:: the MO!.)JlI. In tile SJmaow qf'llw; ~e!l\ Mom! il~mninm:es; he hau:IDy em ofhnmr ]&1'1(1•. t ings fram HI PO][It efview neHIFLy 40 years OJil. OfCOUffi~-:_' it is remarkable that,\¥e:---lInd iul 969 iruU!ma[l[ty took c::redi:t for the M.cmn 1:m;r1du~l;-se~;lt ~ople ,offE:arth dllrillg~l~is 'i1fit cel,lh:uy. SIJ!!ltn~k,OiF ApoUo nlI11Y be ",4,1~fi!I remeJmillberod from iO;jJrpi'Cv:iot~~, liI!!iillenlilriUITi bypeol)]e inthe 3,I]I~ffiI or 41] l:b centut~e!ii. [t i\l also r,c'!Wi!.~~~b~e 'dliU\\;'i;l ~opped gQ!iIg.gw &e
i

IIr:I!d .lo:s8 ,of ~tscrew. fm1lul,1t1!tel.y.ri1l;}t speech neve:r 11:lId t()! be delivered, E<I]']ie!f, \1!1CWe're deadly COl1isequel'lce"s of th e;(iIJe.,\Ve le arn !'lhg,\1!~ 110:1\111 ~eilililooy jjtm.o.1U!~ins 'Ihe gClid ,of th11.t Gus Gris~Qm had beCn\VOir!l,~ed ,!libo~:t Lwil!1:gi~lg men tOlh~ Moon ~!'!d.OOiCks<lfely '~O th,eCOiiiUdiitiQI1I(If t~:-m.ew~i:in!!l:in the 1,00%- Eari~ by the ,~d of the dJ~<]de.BIl!,t .~he:omisoxyg'C!1 ii:t:III1:0!liglbe~'e. bu.t "I can't ~.ly 1nl,:Y- :'lion of l;yr!d!o!l Johl1l18on t~orn tfu.;: lll1l0 'l':LO (l,\~'-e ·k. '1 ' , . 'b I!.~ d t"~ ..JI lhtng alb:olll!tit or ~Jm.~y'il[llre me,' ',c'rhaps; it o~.J seenan 8~tlt!!:b.;ge~tiJ'L~lmI!1eYiy d . .·Uf!]iJ-l@; wasthe~~[1C iliCe:rlCc-,!llld! ,[I glimp~e ofc,igfllr~ lhe~tre;r'S, 8en~l<t1C !lp~¢h) ~cmt5 t~ strrang:e., lit ~n the Houston ca!'l'trro~ room ~tfi;ef because JOlll1lSOlI1! played !tHijor roles by s~gAp(IU~rn ~'s b!l~ding-tbll t ges,ti~g the Moon ]~m:Jj~lg~; to Kc;nrncd!y .nlle] bfi)l,I!:l:ht t~c fUM Its PO ~helllb:r carrymg t)ill!)ugh, nl.t:ilm.g, for "mHdlangl.ll!,g:e'. .~v,ms .fe:l!:'''''v.ii~ a ~urm:!;tE ~y the fil.!n's neat1U(:ltt!)ifreligiml, l1Ie"lllr end, Gt':IiiiIC Cernan .it~ br~ef violf,lllt i:n1!1_ge:S.Silld talk. .. aOOl)!tagenc'mi~ ()l'eaJUrJlI' "~:at l-iit8!I'KiIls ,above ]1~~~deI1M smQhlng~" OMe inimtigl~ung~aclc,.ooci:~ the [,eligiolls l~mlg-ovcm, ollr~Wes,·'m~.d then whute!O~uencemGOn;ls the Cha:Diie D'l'I!ke~eUs aoo,ut filill.di.ng ~esl)Jls".How a.oout the: ,other 1ij M~OOllci<!illd:i,MI!!! astronaut::;.? iI,PI'eElliallCe of .M!II:, and Mrs, ,[).idallY losemUgicm 'QJ~ decide 1:1tI,a:tl\(,:ligim~, W<lS Ar,I1I1ISitIl,,{)~lg, dt's parents, N on tbegaraeshow ., I've' Got a Secret,' No~odJygueSises theirs:
i

the 0!r.igi.111f1:~mms (no s inmla:tkm s 'or reerem:reused). We:lresr Al~1l Bean of Apollo .~ one of 2. the; .ol)e lOC:llll!l.cnOm'; !I:sta'OIl:lmts rea.bred, dcS!:ribe lliiiCJW cli.s!lb<eiieviug he: WOI,$ wben ((l,M. 011 the 'p~]Qine' that the Apollo ~, c:reww.aiS "bst": H!e fi~t <lm:ised 11m!'> caller t:ohxnk fOT Ihe~miun the beach house, bef(me re1l1inllg the
nt:UOI1:l>

And Bean recalls. "SiMioe: tllil8Jt ~iime,mhia'l!c nOI: ,oolllpkl~lledJ !Ii).C)[It the weather ollie sin= glc tiulll.e. I'mjust glad t'bclieisweathec" 1'11e Sh'!Hlgestpif')ce: ofh;ustol~C foot!lgeis n:'ild,l:<11ld Ni,l'!:0]11 bC!!JJinlliliingEli. speec;h to~lle
natien 'llllnoU:IiI(;]~]g faihae of ApoUo the
~I]

lhatdu:ir.'·somJJw<lsrrmde

m,1~s1I1CF

n1i!!l!tooifJ!y.'" Thei]ii~e~ie\v& then t ;lIsked Min. AmnilTiOn £ how s.h,e

",vou~,dlfeel.if her son were chosen

to
]!lIl!d

The fi:~m.dke ctedl by Dav ld Si:l1igon str(lw_g'scool m~mlj;erw",s adr (\vho hf!8 pv("d~ced and dirc;c,t,cd 8Cience miii!'alb1.c, with hus''Olle slMaH srep r'Orma.1IiJJ"" f\J(hili!JJ @dllii,it:;;tJ,l@t h;;td pmgr~msji'or tel ev ls:io1!l),is narrated by Ule ~U!r1Oml'l.n:!li, who sre shewn in c:.w.tre.e he s~elPped OlJ!i!t of fbela:n:d!er clo(lC'ups. '[1':0 at ]e:ut: some of "M, who first, he m~g]w[ at h~vebeenable n :re:!IIii~.c:ll'1Ibc:r thesnas YO'lling Illill:eu w:utll the ~orefnill frem slm1iJti.wg s(lIme .. ltig~n Sruft' (the Tam W-o,]fetiUe.~owbich dl~n;g[ii'::e "'YiI.lwoo,~n.rlU.helJe." seme of tlle,g, refer), itis <I sli1liOckto see .He <11m decscriilJes: bO\.v A1fIll:s'l:ij{)Jrng '~~~.e~I:\:\i'~i'l.e"]l.a]red heads onl:h,e screen. Bu~ d:cddod 10 ":go,long' ~lCm a bou~ .(k:,rfidd \!!I'3.S,llilllld.er the ]ander mmd <lifter aU. Buzz A ~dcill. N e:i] A[':mstrong. and .M;~c·Jiill<ld.comus; were all !born in :~~no. :oot.es flm,t ";itt "vas a ~it:tie~fly right ]ilIIl<ll-dllg daiem about: 11, 'If o Imlay's c()]~e'g,e dle:re ar the ¥eryemi" studeets, tllaH~ film remaias OJmle ofdc,T~ing~ M ~dililliC~,~ Collins, talk s a:bollt clio. It tells the stary ~:c<ldilIlg up lie] and how ~.lefelt iI:oout orbiti. l:1iu,e ~i:ndl!ld[n.g tile A,ollo ~1 missice, then MQonwi !1i1Loll!tge,tl:i~lg ZI chancje ~ deals eurscri ~ywhh~he ]iillissiens fo l[C1wing taland, pOii1iliti.:iIIg outtlia,rut lile was gltJ:d to have ~ i~[l:a!tfirstlanar ]afid~tlg;,. here i:slinle about T been 0:11 the C;re\V of tLliCfir8t manned I.mmd~ ~ !~il.(l usalan R role Iw !the :l!p.r~c~eCjc. The; ins. H,~ tvasn't totlllily\~,iw.el1 Olmittic far ~id e n !of the MM'~ by .hiWlgelf~thol!ghhc WaiS ,~.~I{~,(; .j~c~rplor:.aJt,c 8 fo,o,t~a~et~lat.it~re: g l;ia;rcher5 fm.l,nd ] n N ASAs ~.lous ton v<llul t8. l'IWarethaTthc:re!,;lffl!)(.'l trw'O pccpl,c Oil'! the !mrThce~e@!: ijmagc~.reflect the rc~:~or~tioi:'i of f3!·ee oliThtb(;; o~hc:r ~idJ[;; of the M()()n~i:ld ~ be;YO~ldhe. 3·billklll on Ef}lmt~l,wl~,i'Ii;; t "'over ~ hero. th(;r~'s mle plm~",g,QdonlykT!Q"'¥5, 'r:h!l'r~i~~, ~'!1! Ylili!~r~I (o.~iI1'l~ A~~oo!:l~J¥ lhe ill whait;" 1.lello:~@d Qf,S~r'l:b: '~I;I,[)wf['a,g,~I,e.i.'1 N,~1It A~Jlfr~n!l,ltl'm., 1sat :H opR~rI~IObl!-:N~at)ory. jU!~m~, W ,apl)e~re d.:" 011 .hlSi rdurn ~ fule nml;ar:~t': d. ~ 1II1i~'to\loin, lIll!1. ICl1:l1. 7. USJ!!.. 'E'iII'I~il~ !aVill. w l.on~~.!iVillli~ "Nice: ocean you"vegQt here. p~i!:ne'l: mnh:' E ~ P:~iI.3(h:llf~@l'Iim~1iIii5"@d~

Moon .15~ears ~go.

cl usive, eho S:e net t1oap'poiir ill the fi.1.WL,thQMgh~i::l Q~~'!l.e comes l~p oflicn. A~drilJ SflyFi tha:t Ai!!n-

on t11~M.oQrI. N~Ht\rm~Ii'O!ig. f.1i!gJioi!i;~ly rc-

i
i
'I'

not ill)<lItlk:cl1.brpart f hi's vo~£C to the Moon.? o Earli!0t, Jim Lmr,ell,wi1o road! from (ltrle-sis Of! i\pollo 8, r~p()oo:ing ro a ~ctl:('l:l [:rom m :atheist ,vh!()! wrot~"th~:t: '~tasi.mljj~r,op!iiate," oo~vers, "~be it \"~l._\l;~ dO:l1lt k"OO'\wt limewhcll \~i'C ma:dc: bohll1ilQ~s:' The mm ~sf:i~!~~r.;cdi!S'\,¥Q-nde;nU!l]y prochri~ "TJm!i5 111m WflS s;~ot e~tire[y ()1i!JJ ~OCa!lt~1l 0:1:1
ultet~ "~

A1lth~ ~m~, Siri,g:t'OIi1 Oi~~; a mrwing; tiib-

I
..

r,,~

Earth, ~n SI~ce a:nnd the Maori" tvrl

ro.1l~61.1id!!ACf!J:.1"l(l1.ol~

BOOII<S

ET AL

A TASTE OF THE ,GONZO SCIEINr~'ST

. .

me·n.t? TI~@co,.rder,@Mce or·garll1liz@rspetr~mmE!d a pla,y inl hal'ldmaldli! period (OlstUlffi:es, no leSS=aOOUlt OD1;E! I@xuao.rrdinary day h11 th@ me of Ijnll1ia,@us. We ~r,@then e,:(IPosed110' ,dalililce [Hille of tl~e t]me"ru~e ~he -. f YO. milii'e iIiI'~ heard the news ye1~ 'lhii$V~fll~ 1m Ilksthe 3(m~h bl rthu ..... day ·of Carl~!ll1liil.;;ums. ~ (alii re~iort that ~~lsrIE!llow SW.edle.siue' k.eenly mirllJe-t i(lm,glliil8 SarurdarlVigM,Ftwr. but with MDzarU 11 :jliWare. (llnl {,!, ~e(;ElI'ItV1s;lt 1;0 lIp~:sa'la, I too~ parlin 3 ilinna!l!i!Js c:el.e" if youl mi5:~,oo '~~e~Ia!'it~r don't. worry. TlIMii~l.lCliris 11,0t~l dlQi'le.W~lY t b~attio,., o.rganllZed bya gIOO!IJP of SWllldis:l~ .)lcholau :ilII1lC c.h~fs. U. W,a,~ not tJmlW a U I'Ina,sm 3OJ)t~, b]r~~dlayparty or'yom own? 1lJ~:ehe foUoW" c3ll~d '[,Iltina' .MutQta', l~e eha Ilgin gl Id'licbe n, a IfId it W.Qi$ ~~ e 1m os:t 'ingl pro'to[:ol~ to prElpailr~ a Wlli'lte"lrr fea,s,lllmi true' U~lnl,a~n style. [The redpss (bd~)' awefwom un!i.:!51!.! a[ birthday pall1y'llhave 1(l;l,IIer aiU'e:nd'ed. G1!I!flflar Brobergl ~fldl G'IUlliHa UWlllITla~llJ:5 is best kncwll asthe inll,l'ento~or modern UfldeU'5 :rill ,(j:vs med [jrme ti;!xonQ!lflY~the system IOif Ulililni na~)es t:h'at. dl:vidle ~n ~Ual1tlis. Slcdh,olm!, 20(17).] ijrg.lllli~·m~.ifloospedes based Wir'5t~llm!d i;I ffiish. The wiDlltelr mil shared 11~a~!5, lI~e 1111U110i'f~f .11M~ ecee 1l11~ S~· m{ll!illh,~ are best fQlrr the nJlth\!'gillon hel1P!ed IP', remaf iIiI ,at the forefront off·o,od sdem:(l U!s(t,tll'rn rod :1Iy. Wi~idliii ·ro eds iii I:e n;ecessaryford evelopm e'rilt, and \!l'hti {~,sllinould be .abo known as the wo~)idlgrouse. BUit lb,ewar,e, ~hley ,are' 'initeIUjge'nlt,alnl~ i1I\I'Oi:ded?'lo wllat.ex:tent (an dlet ploomcr~e!Of ltlilhilbit di,s:e<:1Ise? Is there an .agile Cl"eiliUJIf€:S ...¥Oilll will tneed 11 wiidB1y dlf5persinl~1 shcn·gull,. if no[ an id@i1I~die:lfo,~ lea'ell pei1S0.nl,orjndeed fOt~ ·@adl g,sl"Ilome? ,amO,llIIililk w.eapa-IIiI'. CI~.'ed.what toea lllflli\is !lIIPpLy. Safer thr·e@' days, ,ill di'wrs@' me,dl~y O!f Il!cadlf!.mk~](dElm,isl~, On yom way bact to the !a!lie mth lIDij i'ril ha I1d, ma,:li'(h to ~~e rds ~'IIlIilImpto glal~.er(rail'lb!ul~i:es (Oxycocms: p:a/u.seRs). ¥ou WiW~find ·them h'stQI~ji!!ns, agrkillLtutra~ oc~@'l1itM;l'!;, psychoiogls.B ,@xpou~d'e,d o~nthe $I!i;eoce offoodl, Iboth lml:the lifl1l~ C)!f tiinli1lf!e,~s and 'today. The I~eth.ns in Irow deprre<flstons b(!ne.ath th!!2§iIlilOrw, IfVOl.lf fe'Bi: 'get w~t, Ib,uild alir,e. BeUertQ rluin a dilliner th\\lr!1 leseatee to the frost ~lOIHN D()iI!~~m!lI~ IIIIlllr~ PUllct.ui.lil,ed lb~ aseries of 1.811'l-CE!l1tUIiY m~als, starting withia lOJ,!!';;:6?l;d~l1Ce.U.Sl,ss:l peasant's I~~ri:~h e'miding ~'l'ith ill. ~lQyatl b~nql!.!eL,And for el'ltertainiiilmid

Ffi~ '(01I~f.~Uliie:

g~J(, B~n~t

the·,f.f(;,~~fo.t,r;Jm:r~lft

Wlfl!U~r~~b(!g~ 1 h~ardl IColb'oolg,t rd 3 .~",pl~~ eo ~, s ooseiat '~Qf IblJll'lter) 1onio.'I1I

"1 rili]dI(lIrp~ 3SQ ml !!:t!11l' ~~~r 3{) 1ifI1~ m"laSliiies 'or l~cll1ev 15 m& Vinegar 10 glsa~t 2.5 gl wh~tQ II'!~pp~r Me:UHrll!at ami (JJ!(};~sJi{edtkJ cabbage~'lId t.IJmd MrO.!'l ,ullrii J(ght1y blown'. Md ,~,e-~~slked ~ppk~ tfui {lO$kria.r1 afld s.iWl'!e ~ttr~ Simme.f wi{ertt! l!ntit th.~ ,@b~€If! i~t~{lder. Add.J1I1(lre w.tlter

1(~p~n:ali~~~ 1 ~6!rn stk'C of ~ro' 30 9 fre~h Dutlielf $ah ilIl~d whr'ite pepper Gr~y; 4~59 b·ut~f 20 gll.our 3:50 Irml (~cream,
15 gtabl~~p:o~Ul )aU wh~1:e il@p~nn
CU

ifJllGllf~f(JFe ,rJ'(iding t,ile «(.tim aCfld i!JU.y, rbl!l~ In I:l S~ti\C~~i7 J'(}t
:!lOOt' miflui1l1.!l
lVl)[I

1m1lrJ:gtll

rmtif t,l t,\!l:SleS Ii'~gh.r.~l t~jint! cmniJr-ttiRs, •.

,(l

~'~Y W€lu.Mm\J1k,~
tI1Ij'fng jdfy;

mf,~ J!lI'WJImpti=

5 @!Jg~ 475 m~,milk 11s: !ill traisirn; 2..S 9 teaspooli1 S1ll~.

5 rnl~~:Sfl'(I(l'!il·l~m~~ l,u:i~~
Riai.e: ;ti1eMi£,ifl5,: dT'j til em., ,(J'lI.d pla{t in C/ CQh Jl!'>C111, M~n.whiJ\·!5'. rh~ul1!l·~r n~ix,egfJli ,(1fKi rml'k./oij;Q~dby:&o.n~~ ~/,~ fl:l!'dl€JiJJl(lf!' j,u.ke. fkmslQwlr~ ile!ticw;e< jffJff1 f1e~t wflffi it tlaftS ro rutdle and be.al· .s],owl) iDNJ./bt .!Wl'lIi!!l1es;Pt)lJr t:hfm~rc Oil!?!' t~ r~S~jl~ Qnd plcr::~the p~n,n ,(l ~I)~ plr1re,

h(Jli!fl~ .~ 't!;l~~fl

~r.al'it .~e~¥

I,~ pike' .2 P'ik~.ii'!~;II;~Ult ~!iI!each l.S· 160 III1t me:lt~dI~liesh Mtle~

~a,9

'9rfl'lfld h(yf:!ieratcl1s~

P'Ju.i{( ,r:mrl,gllt th~'bkd. Coaf: i~,wi" ,alr:vhoi.«fld s.~;f ,J!lI%lbUv sirrp'f! ~h!l' je-o'ih:e:r!£fl1bs. flllis!? with MJlel. .f.ig/dly c~~t the .iMw''e ~;'fh -salt .BJ'odtfie k~ muljmteJI ;fhe ~~eI oj.lo;mQ~r tlie ,mil w;,l~ s~ e:l~ SptiFlld,r:genemus,{y ~'th :m.ll O~p€'p:pef~PfJt the bifid ·().1I1 ,r;J ~l ,am;ifry It with ,f! bJazil1g fife. ,(;~tf'lli:r ~'€' jiJt as. it·fi1111~ b~~'in!J' thllili'{} ftequf:fJM., to p.r;r:v;~mdryfug .• (1)0 1J(lt ~d~\I'~tfm~M thj~ia{). A k~W'leflb(l!lr~~i~d} F(Jf tJ~'

$ai~ Gut a.nd ri'llS!! dtefi5h hl' do rnl't ~,{ilie'tmm, PJ;f;f(einf)oll!J¥j.mted ~tcr !lmmeflde(.r,lfld.s~~ r.¢~·h

melted b~l'er .r;Jm:lg'(J·.ted hQ.~!mgdisiJ. fh.i'!: d'fl'!$SJlr.g

orn bft ,~trlrv~flet1

rwiffl· .0 ,tG!.fch 9flt!I'I't!!},o{ lJ'I.l'll ~!J(goJ': ntor1' fjsJl' sJ.lrwld~p.rtsenrtd fitJ~~ (l,lM.g :with dfifl:ll:m9 wo.!l?~,M~r. brlrl~¥ br:Md_ ,and ale !tale ,of hli'~

c(JR/~Jy, TIl~ dishstroui4 il(live ~ mild ,CliJd.ple,Cl~am ~~r1l-5WtBr tGSI:e.A1JGIt':2 .hmil's to! ti'l'is;
!)'{('fl:$lG.JlliO.U¥, S€I:lSl!Ifl

Wh.1m th~t~,kr!h~~ .tllf(feJle~.5f!f1/f!' Iwit:UltJehttty i'll1m'. lMn LWlfUbe~ktpylJjl'el Jthi~Mlfn.d' t:he. (l1n.o~'I!S:.
Do J'J~1'mm doiW/l :d~f ,lW!l5Ol? l

rot!' lJ1JJg:ilr

ltbefl"l.

R:ecnipes: adaJpte:dllfmmG.I!!Innlllr B,mber~1 ,all11l,dj(j,unHIa lil~.deill· 51ril~' wed UM.e (.A1l\a~~'5. SW(Jkholim. :2007). b"vs

:2 NOVEMBER2Q07VOl318

selll~NC~

WW'W;.soier'lC€lrrH.'!lg.org

BISASTI:A !MANAGE.MENT

COlnflr'Ool't:iing ID'iis,asler Losses

l;i!'1(!!lens, M. Elo,UWe'J;,1!1! IRyi!i!1l ~ IliIo.g;!r ,A.IPli,ellke Jlr:A
ICr'Q~p,too,i

Adiol'ii OJ:! di5:alS'tE!1!l !'i~~~ldlJctEonl

iCa!il

.o;ulli'PO<rt

'$ul!:t.;i'inahle d~iIi',ekip.me:nt UJl'lder dima'!:e' cbl1g~.

Eberhard

1F!!R;,!$1',~ ,e.ter 1iI,iip,lpe.~ P

to U.S.84,S.1 bi~1i,ml099'7-2006)., In CglWlj:ng decades, ~~I(; IluQlJ!beJf o:fpMple .-u riskfrom c;ure1mi1lcslf.,.i II Vt:iry likely grl)W', <lnd C)::trcme
'VOOt~l~wilUlikdy

G
_

~O.~.1I~O.Og.t~.:.~f.W.:~ -><II .. T.'~~.I.il.E.' d._~.... n .•.. _t~le ... S.:.~ ....

!i.:~ ten; hn;vc jncreased from alii ~Iln~m~ !J.~'enlgeUS,,$.8J" biUion (W97f-198iS)

pjf.~'1i1]tei:lIiIIS'UrliIm:e

It;;O:I!M5t:irllctiJotIS. :il}f.i,stiw!

de'!''e~:opgeJ;litfi]!l<liglCi!lgw~~~in

~Qc~1CgJjlmiU-

~~[d,l~"g,e and eeenemle dc:vel~pmc;TIit ~N) m,~ill'D;ly ~p::m:sib~e: fur~lcr'OOi~,ingIS8e&" AI'Ie'i k

~By:2,[1 J5~]OiSS ~O'lel,~liab: i!lmQng the: "",\ornd·s

t1iiicre..~e,(1). ]'0 dale. secie ..

~djuSl:inslbr

re:necl tJ~eo~iln:aook,~:ieallJ~ord, (2).

societal cl,'nan~es. loss 1!ime !,';CJ~es

]]t'C:S!J!Idlpro~!(1l' ty 1m;1icromsu.lm~lC'e t'O the: most 'i,i'!I;J1lnera'Me. The World .Ban].~:-!!porml~.i)mdl Ca'ilbre;f'!u Cat!lslrophertlsk [m&;,1I,I:mm.:eFad:li:ty oilIer.;; govc:rl1lmellits, (Jove]" !l,gai~18tli!JU!~Timrl1l:e!>

f!ili'~j.fO;r~xfl~lp1e,~\'e.~l:l~U mf!&. for ~rr~i~ inl"hl:stn~ctl.ue ~mpim"'~:Ilil~!l::nt~11E] Su;lv'Jdlor:. -, 'U- -. rt risk Cl!i!C._lL_. (()~ I. ~L _ CQ· .... JJ._.lf . H ,w. nd - ..mm,ni'::il.ptpOL f,!" ... red gro~tpS :m.lm:Jiowl~'nt'i,;,eleve~oped! d\;::fic:ltmtntF.\l.~.~ d tjl8yriiflCe ,(9~. hi! Coknnb~<'l:,. icrocl~.tr~'Pr<em !lCYit'S t"ff~rS!fF~nbble and e~sy I,'Q UI1<!rcn;laftt(]
I
u.

~ <0 !m,"g,est aiti,es, .nost OfWThl,id~, in d.evel!Op~ are :ing cOl.:lntlrles,,~n~]lmjeded,~o ]!1CremSefTOIll 2l % (Tokyo }~O 88% (SI'l<li[lgh11,], lII"al1a) (3), ~ A I\epea.t (lithe:, .hJy 20{i;J;fruooos, in Mm];l,tm] (see:r.:gt~lie-.. r.ight) in 20]:> c(dd cause gO% :!iIIighf::r ]ossesmui: aJftl~Ql 20% mm-e peolPite. iJil,deil:H'::m:bnt ofdi~.n~te dm:nge. Greenhollse glls emi$siolJl redluttions a:ro ofce.]lItr,1l!1 impm~ ~:d!llOe, blJl: they C1lJt1Hot Gecl.'(!aS€: . .irullzlIni.ri,s.ktb·r

aed

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with [(1mb a:\'3i1a:b.~e,<I fe.w

day.; ~f1!eJil:he 'e\Iil'll~t:(.J()., l'he MtJ!IIlilC~l (li_at:e lnsurance ,IHiti~tive b:r.in.gst~getE1ter tille World B~~l];. insueers, nOlil;goverlilimeMlttl'~ oil'g:::Illh:;<I~

t:ions,. and the' Sicie"Il:t:ific ,cOmlllliU][tyto de:\!'ie1o:p

tUliInce soh.nim,lsibr
lIrli<li]JmdOl'l

i~il,deydlop:i~~

cotm.tri.es (H).
:If pl!etleJ,u.t trc>J.1!ills ICO]1I1:inlle,£,IOIbll~~ di,s:tlif3.llet biSeSW] m ,kie~eiPo,utuPac:i Il;g "v,e~:Hge ece ~ nomic gw'wtlil. Therefore, dis.rustcr Ii".is.kllcdueriol'l li1II,lIi~'I1De [JOl'te to dirml'~cl'ldO\l!'pUI.ti.o:l'I WllIl1!t i~ th~s di:sasi!i!'r 5hlo~ddl ha,perl a:g'airl1 poHei (is. Ntiim ~roii!liS m~~h~i"i~sm:s for~etiOiil! ~i5.~: tiliH~tC!an cO;nlribute to tlm:e ilim of S'l.lSulinf.!bl,e d:~\1·!;'llop~e!'!t..
R@f'l!iIf@l1!i!5i'100 NIlIIe<.5,

d!ecO'Ides.Iu this [101l1!el'lt,\\fC olier ~l~reerecoQm~ . D:el1diMiomfrn: dec:i:!i:iojl-makent

limprove data ·i:ioUOO,l01il. W~lihf~
exoepti,ollS,.

ere of iP'OOf q]t.l!,duo/. • 'I. .1 'II] ·"1' .)] !~uO!1l!Og~rlCO'~S. ~I'!!'!! ~o~.~roy u~~nga \'l,n~e ml.lg:eofrnel:hoos f'(lil" dj)ifC:liCn~pUipOSlCs,. lU:ak'lifd~~~S'!elfl()ls~Cil

roCONg

il'!\g rc5e~!"Ch cM~mdy

cl~Ue):!l,gnng.l!ltp!iO\"(Id

dinltl!!could be 1!1S('d 10 cvall~lC di!ll!!S'OC\r ro[~cies, eS:li:mate return pe:rlodis .• iJ(Jle:nliiFyl:S!c1.m,s t:~!It drive IOfiStrel~ds, ~Ild oDuldpo:renHaUy ,offer

~r1d~~n, dlalbbaw811..n Ounch box Gmielrs) 'wl!l~k ~l;lrOI.i:gh, f~oM erl ra1~wa:!l a ~lraLl~.;rheof hHm~IiI.Ual : Iri:i~fii5pillri.l~V.ii.iedj ML!ITii~llIi., 27 July 200.!). The city':!; w~a ther' bl!llre!llill said that MlImlbillilfe(l!ive(j 944.2 Imi'lrim,~I.ers; 07.1l ~Ii'lche~) o:~rra1Jiflf U llfl'l 21'1ililom.~, a

Inil!!Fg·[w.I!tllifileiilal. rid ill'lii C:,llrl'l:rtl~CII~1i!l ~ ~ PrO. ~ C'llint:n!~ aM~ 2(I('J7 ~jP,(c,.(im!!l!:l' 2DQI7j, WL'lJ1IJpOCJ~h. ~" I;:' A. IPie!I~(l f,. .. ~, Lml~M, Bl.ir~.Am,Mt1e"",m" .S'oe; ~c

:to

eo, .lO2l! (1999l

'~:~e:p:roiSJ;1<cct 'ofm~, arly·'w~rlilil.lg $:rs~e:mfo]" e ehaage is, .i.mil e.SiI.'li.iiIH:!:!. i:ma~e sySlienl, 01r~ the :rent'1y. the :ooost c'OJnpm!lhensive fuiS:!> d.atalba~:s are l1i,e~d y ]~'I.%11I"8[1\re oCllllpil!Il:ties, and ,~re nor b prub]idy 2.vailJble. An 0lllen~somme. peerJe'!'1Le..\lCd d"l:a'b~e '1!101iiliI,d, e],l<llbie t~:l.esc;ientrnfilc cm.umllilluty to stm:l.y W'C!'rlcllw,id,~disasters,

to ~n:appiro:pri.~ue·val't!a:~,ion ofir1ive~n1I~lt.mt ~Ild fillllimJ1cial ca~c!,]hli'lli<ons: in misk.:reduclng Me'$sures (51.. Ris:k reduct lon is: not 1I s;wl!),]1y .00felTed ~o as cl,~m2,ttfl..di1lp~:<Ihol1. hrut may be de$c'i;il::hedills lpi.mn brelC(h~l.g and seleetiou, lood~n,iS:k re<illm:ti.ol'l,. pM.bt~c;h:e',<IJUh Caire, lIIuj so on, -1)\~el,Opii]ll~ ccuntries have nmny
'0I)lPort1mti:ies, to Illltega.'<I.tc

<1.Ii: •. M~t~!.!;:r,'o~~e'f;I:'fit.4IJat:%;5 fI/ Mliif!oW!i

3.S!e Supp<C<l1:i!1g1 O!l1il'!~~l.iit~ilJl~~M),

[GlIZ ~GI!lYrIan :SlIlth!t'llI~1f WlM'ittfl'ical,(7MIl'!!~a~~fI), .8tl1i1Mifn,OMl l s,. (. S~IS1N),'. foogg. ~ll1Wtfng t.1ili'gMM: tilt!'lIrM'O.IogfIl'S
TN ~l!1!1'fIg

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~l!l~liIfgaoorr ~PH)~I1i~Dn. UEl!!eViJ,2~Q411, 6,lt Fm "I, Q~bil'l!if, i~~~r;, D.llin~r; lM. f.S:!l"liift'ir:JQ.

alilmme <I.m.pt:aJlftOlJ]I
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~

E,~nd

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lE!da;l*!i~]OIl1!' The ooSl;,:oo.lJiefirt rn,tii,(I

of diMS'rern"
lc,ad,s

in dis<I,-st"';:'r :Ii":isk"T1Cduct ion effeets (,6)" Mo'w !ell,e~,cilny. disaster aid is probalMy best s;penl - '~, " on.ex, :mne m~: roduenon ( n-...,' DeVl!d,OIIJll .apiply i~IIiIOVai~i\li(!fiili!alil(~ ,!!iIIl!!!i1 m.e·dh,ai!ill~sms.lnd'li.lstne8vdth grcO'1!test~)!qJOi8ute ha""ere~pcmd!(;ld to ~~l(:rca:S]!1ghJ:;s(.$w:i~l\! iIl110\~b'Clprod'1l..e~R Cal;,ll~L1iopliil:~ bo!Jd:s arc a ~~la!1i~m ijsooto :~fi;~ pcruk ri8lJ:.:s to th; Icapit,,~~ markoet~,wHh ~her~!i!lge 'ofbaz~~rds ,ver,··d ooIlitiln,~1] co f.. X -; rat:IJ~1r Cge_._y,~ f"" -.- n,u- .... ~o._.e_ --_ ... ,-L.S _QC.p_._~ the ROQdr~sk~,in die UJ:" (8")., Pr,evi.o:tJ!!s:ly uldm;uredtilood r~sksi~~. B'fdgi.1)Jlnll the iBlnd
1-'

M!ii.!lagem~r 511.iJill~i!lMe' JI'>o~ro/.I?ttlildirm liJulfis~Mlll" a~d M~pCatl'(jii 1i:~,!lJ[jM~Gr~mp 'CVAitG)"

WMIIl ntglffill, i!l(,~()061; \'\f~{/£rn"~"~~r>!i" I, L11~lltf1)~~I·e:irl'i!:r, .M.I!dll.'@t G. ~fl~ .SdeltG! 31l~'. It

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1044 (2005).

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9,,, JIIlliam, pr~~ Il!ll~:re, 10' Apfil200:il;

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. ilJut e:ffm1;\'i remain

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of ...

UlJ!de:riI1U:ndcd, l]]Ipl1rtlnd<l!r~
CO!j~~ andoorlefits

~. 1111'1!~titut@ EIil'o'ironIni!n~~l Stu.dlil!s, Vl'iil! U ni!l>l!il~t!!h, I'or ~ IImd@rdalill, N@tlill~rlands,. "IRi~!I:, Il'roml@'FS", 1M:iI(quillr~ 1'.1 llJ'm1f~r~H'I'. S'!fdlii~yj. All! slJ iI~io'll ~G €\O IIU5,~5 l1i:e5ilm:ch ~ El'ep.al1m~Iil!I" Munith IRe;, IlIIUflieirn. ,e; ~rrlIlilriy. ~Cernrer r~r S:!liI~1i)ce ~I!di T'elrn nologi!" fo.l~1!;y~~eal~clh.1L!l ni~~!'~RII' of

10. Ml!lmch,R!~ p.~e,s~ r.ea~~, 1)!Ji1\lt 2'0D7~WM~\l1IIl!Ifii~I1~E.ml'li~ n. Mwnidil C:ltmai.il!,II!l!iUfilffICoI! nml'ti1ltWe, _.~L1fni!l.e· in~llilr~fIU!Jl!!I.

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Su ppll~liru~ 'O~II.iI'll~Matl!riall ,Wl\il'll.!id~ifl!l!!;!rna@,!lWo:M~(irrt~MJliJlli'3,l8.i<j!l$lIJ;S~OC1!.

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Und!!!WSt1!liU::iillrlQ I1:DiI'Ii i.l fartQ:~ Si!!!( r~iI:@d by IIf! eUJail IJIssue'I):romm~s n~ Un'll:! r~!1lf01Nth ;1it1 ay h~~p field I~f'regemle!lati'lfe' !'!'ulldid~'h~+

me
]iblOil!ries: from tissue and . mals, ~]!IrV~,r:I!;lbnJ,tes" such as spon,g,C;f1i. MI.I;st~mi'l::i! wit:i1I Pt,od-l pro,~ydil:l''',1Iiild nahVQ'Iln~, 'cal1if\eg,cnern:~e e:ntg;l)e teia . .hod~lis a cd~Sln:t1u::e org,mi.l'lj]il~,iom ~1H~:e di!..~1li:irQf celk A':JOOf p~.·m~iu ex;[lre~8e;d~[ a pr'w;;~Inal-'l(J.-;~Ii~t~~ gfilidie:nt ]r! th_(; lp-C!!1l!.brares.~philbia~lS (;rmrogene~tc: ~imb,s

'T".

"..~.1e <l.b.' t.O'ItJine-s Si!etdly .. ,i.li.ty.... .nl.!l.~.I.<I.·,.c. ·~.Q.s.t e. booy p<l:n:s

00.' r

~ni:Oi"ig .mll~

dl[[Il.'lI.-ge~ ..

eX]lr~sslon

nCli'itlallimb

aJlld other c(li]'U1!l'ilc:r.: stl"U(:lures." Oe~pi~ a rich newt limb regelilcr~t~ on irl,g:rtAO exV(':SSliol'll. \\ihilJi:: b hI8'~nHI. ehai vcl~ e(:E:S a research l~istor:Y'\;vith tlJl~~ !fiIlodeolorgt!!liis~llS, 1!a;nm~eli~aJwd ,iiJ\~:1i ~il1pOl'<i,'!Ill:: ~r,e !;;tm] dcdphcrilmg h~w ~11C<!n cells, Cl~m ,g;r~di(;llt'ef cd~l,!~ar ~~en~~C~lC bia.'ii~~rrUl~.'l!it cl'ooiW~ertliti~tion (regr'es.sil()l1 00 a:!i'!Ile~lier. un .. ti~nalid:enlhy (8)10 Tl~!e~il,l'~1{I\\f$+ A~ Sch\~r:Dn ~e~.\ll :s.p;ec]al.i.zed ficum}, ,m~ds,eci.t1e, genetic and tlmrs show that nAG laa fOrm .aJmyelin ffi~iflalh aJrOtl'lrnd oell:l(!!.100" Dgl:iiill:illg m~ed:19r1ii:!lms 'ooruirl:d ~11_~:~secreted ]ig3!I'idFor' P~rori-I. $ 'lrnewli:rrtb ,ax.ol:llO>!h~y'l'ro'l!lld ~~·o"!.!O!th (se;e d'l;effigl!me),. On I!')agJf!: 1'12 b:lllli'li:s Ibee:xpeL1l~dtoresume MOI1mmd ~S8Jl'~'1i:lomen(stimlJl;aJ~e:;; 'pl.'o.~[FemtiiOn)far newt 'Ma.~ im;looed nAG expressieu, i:ssm:.llGttm,<If el cd. ,(.1 }report~~le d:iisoQ'!;re:;y s;i~m1l.ce]]s., .lA,Iring the e~11y of ill ne,w ~nolleGJukH:' eue that p.':mnJ)1~S 1.1mb A nl:!'ljQr ql1esitiQII1J :is dedi.~el)eni:i<l!t ieu s;l;E1ge of' re,ge:11H::I:a t:iOI1lin newts" Sucllil, iJm!sigilinls cOll[d "vJ:letber 11AG-PrOO!-~ .i~m.le["~ ex~lmnwJ,~y IllfllmUlllb have [[mited ~'e!'l,:owth nc,wt limb I'egenemti.o:n" :11it\G' action ~~Ilks "lfIIs.lema IH'O~ liremno]il, with patte rill" ~b:ilitic5" and lue~pgluide fue"eMof[l.>:ge:neJ.'.a.~ wasdetec~,~1.1 Sch\\lImul cells of the d,lstam nCli"'lie shesth; i:~'-defin~ng the:prox;i .. ~ive medicine. Ne,lWt lli~1.M reg;clll;:rille by dedlifJ'cn:::lJllIiating; mimi <lind drust;fl]lIe.b'iirnil,s,-ot' b.ter. at ~JrniC' em':~y b~d stll!il,e. fibroibll!J!SI:, muscle, skelletilL. and w.:JIU,'lemlm!lI] it was e1!.pl.'eS~>[iJIillll gland! cells nevo'limb pm'S. R.emoval ,of (SC;h\\i:aJm.l) cceU" of thenervens :syste]lm i:n~l] oftll'lle vm:l!u!d, epid'e~.mis, P;rodl...~ H1(lm the bjasteJll'~ 111 Hileiw em:=]]CrS,t£lUll [eUwl'lIiIiiI. These stem, cells cell slitfllCe. Oli' its: ililh~b]Bm i1~\7!'id.1.<111. other mi~~ n~,elm!pruiirerate to t~ 11.rrn1:SS ·ofl!mdilicren~, ,S.~!~futbhl;~i:cmaee~I~s, dime!: tion by ~rod-I,-specifi,e a!:'ijtibody~iibQli,8ll~!'j dHJ~tio1lltedi CC;i!!S, the blil~tema" in aprncess '~hii,t iii v:i'!,!:Qcvid:e!"iOC for seere(?il()'e8 i]!l ce]]!idhe~ajfg as~oroqLiii:"es rncOO\l1iIih:iM both thenerves and tien ofliiAG f"omt~ei:'iefVC (lv~"fl)'ing \!'(()u!ld ri:l~i:d()rnli:s ,(2), Ptbr,ob~i!;8t 5:h~th~~Q ~~tK'l tJlf!S~a \Vd.s df!,t:cdwid~ pr'o)l;~mQdi~'!:mJW gW~:l,fth ff!CtOT-2 (.Fgf-.2:) {3)o.!gH~I. growt'h :not dCflnon8tt,W~d. Ho\vc\l1i;'W. My.!ltery j)!~ ir~gene,rarti,olll!. Ui1Iidie;r- pos.iti.,orul.I. .idel1t:ity of ~.1!nAO e:l{pl:essJQIl ~Il glaJnd ${~fIIr1ili'lg IfllM v,enebr,:J~~s.L1di!, .a~~~ S1!)]1l~C!e~n~ ,and oven;;x,(8). roctol'-2 (4). the ilet'lro;h'anSln~~t~rsnbstanceP (.)),fmd the lron trol:!hSport pII'Ole]~lIT8!11SFemll cells reqllJi3:ed a IlCrve :;l;~pp:ly•. Iil@\m h;h!OW!il~ (oi!!iI I~~row boojo .p~rrl'5 pression !!)f:P rod-I resuhs (6], IHom(l!l)C b~!lste.a eell pn):Ii'fura!d(n~. In MOS:I Sipe~c:u!a;rly, ~nt:m- liilJ'IiI}lliIave klflp'lica.t~ot1!isroOr fe[te neral'" in tile :prmdm@~ 'n;!l~~::doca~ fli'(J11Ii1 vino anrl in. \'['1,110,. ~!ldFgf~2-:!;o.~r:] eads sop .. dlJcti.on of ~lAG DNA (by t1\!e' 1fIl~~ici~. iM~p:~~(I (12)]1 b [tOO of d!!.I1tail b~s1em~ 1Je]1lJ:: pon re:gen0mtklll ofdc:nm'~ted a1(;(iI~ml [imb~. e]~cn'l)pOll"S'ti(iln, a ceH pettrSln$I~]a:nted into prO)d~ll:a1 I~D the point: of :tol'ming di@:ilS whe~ro.impl:9iIncd me:mJb:ul:izajti(l!WJ~echini~q~.e)"estoredregellc:m'blastemas (9)1. T1ro;cresults ofKuma:r et (11. lion to digit S'tiages'. wiltliH)u[:plJmno<ting nerve slUgg,est tha.tPood~ I. is .1 i!<ie];:t no~ di.r,edly i:l1I!tO a ~.!lstemadlat has uireooy al13l11led a.cH1Ji. ieal mass of eells (1}.. N one of these l1I1O(i~e,. :l1egencmtionilflto tin,e \1!'O!l!m.ded li,liIm. ~nV\o]ved i~.l s:tnbli:shiJII~ po:dtiioIlOliI. idelmtily. e cu]c's .. ]n;owe'llrm:'. has been pu~:~o the ri.gol!'Ous Thes>Cl1es:rIUs ralsesevesal qnc;stiiCll:1s•. Is: bl![l reflcl(:ts the 'Il:roae:ss:tllli:a!t does .. Prod-I ~es;i of supiP~ort:ing :l1egenem;timl of iii. denernAG IIJ11Uiqnetar reg;ene:r<lit~,ng limbs, or ws: Us may de~~c::~ gaps in po,stt;iOlUll ide:'IfI;tity. and vated and fl,~,nlPld<lted, li~nb frul.n the e<lili~Y saceess a:ll:rilbul<llbl,e to its 'co]iJ,ti.numn:s ~Oll~~ iU.lfO!1J1ghits Hga.nd nAG, promotes bI<lste'JIiIl.<II dedifferc;:,nti.at~oJil silage whenOJ.dy a, few term ezpeessien, im:hiewd ~JiuQugh t'I'aJeg.ene teH pllol.i.fcmdol.l. ~o f'HI. in such gaps. bI<lstC]1111a cells ;m~p:resellt, Kllliilll!i!ir e:t al. p'<ISlS ~.lect"UI)Qmti,ml strtlt~Ky?W]mlfl't is. []],efhnc~ O!r~OInilrillti:QnOf~~:l,ese cells ~s then fnrt,her thi$wmw:~th <I,previously HfJlkll()o1i.~n !lliClor mll,t tianal rel:fl!tioll between the nerve :a!Ild. the dcru 111ed by o~]u,er sign aJ ing rn 0] ecules \\iQlI!rld epideooi.'s? The 'l!1!'01..u:IId e;pide.tm18 is ii~.lvolvedillile:mb,ryoni.c limb deyclQpm.e:nt I::;;e~ressed by limb DiLeITVCSi. The, new f.lIcl.o:r is newtlllliilteri!o:r !i)[.iild:icllt il]s,oessentj~l. fOorbklsterna. :form,ltion, and (10.11).. l'here,g;ene~rl1tiQrI b]~stema h: a self;' (iIlA(H pn)rein .'llI()MoJiog anile k/jq'}l;I'S l:a~ mo&tlikely providJes pDJli.l1ern.tion f<ilctJor8.w,::ry !.'i:~ :sec~~t:ed pro1:e~r! XAG2. ,,,rhie]]jslP<cc.ine:s eartySifte'r1!liW!1pl~~tilCll'L &ChSI'll XA!G2 s,i~!la!-, oijJ;an~z;iTl:g~tnu::rurefro;m ~uili1le~pUoll> but :lJited!e,,'Clop~e!ilt of il~l!Crior Sln.l:tt1!ll;flCS (!:HA.ch inS;~!'!!lf~~l1bryo clC~e!'!(jIs OjJ~ Fglf's.jgmdliVCdO~l't k~lo.W l~!O\v Sl~cdn,cs tl'!1C~f!!Ue'm of i.t t~le~lmv Hmlbo paliit'S. One idtWIis 'lh'llrt:prQN~rlU!] a~thtl 'forOOmin} mlri~'!glfKJ,g e'flilb"o;ell~~ii! ins: p~tlnv.t!iy Might!1AG Sf~i!lilins aillo (i}. Ki.!imar ,~l' al. ielcl.liHftedriiAG by sc~e~i:qg dcpe:!ltdl ollii,l~g;I:2 :If(j!~~ 'th~;w'()~d t.)pid!eml~7' arud dlistal celli.i bw bOlii~ld3rri~~ ~re ~elt up simuM!JJte Qij:tdyi~ dille ~rly b~~[:it~m~, wilh ~Fu!!lher!liilQr'e;1 .R,;;l ~he lih"~!!fl,te!lla:~w~~U~ disl

T~:l.C mOSt lik)e]y answerto • f.he ]llIst q;!!llllstioilis a~Olls,. t:h;e ce~hdil.r (;,!:K.~eIlS~OIi!iS of ~ltC'1.I!!fO!,!8. SChwllli!ifl! oel]s diediiftl)~l:l.ti,.Ue <lnd ente::v tillu:e blmMcMfl. pOOS,1i,[_m01lbiy ]05 ..

<n

'!I'M ,a!!UiO~ is e
Mifi9.i,gan

Ule Oep~ r~!'I'!emt 01 BioO~09!i',Illa!"n!! Uiil~'i~r:~it.y-PL.ind~eUn.1'!j1~ul~yl:m:d~lnapo'lis. 72:3 "I.

St. Il1idi~nJ,gpohs"
liN 4ll202, iIJSJ!b ,E-ma iI

r!ll

IM~UlITrI@ti 1p1!i£dUl L

lOr.; 'I:i~ired. Does ·oo!dlii:iQw'.S1[ ~AG ,cOImclto!mt.he wo,M;l1Id epide:rmis:? And what Jna.i:f'lit8:nI1lS, 11iI1AG synthesis I:I~ Sc]:IiWi!I.Iln oeUs'! s:he;;l:H:'I
1ll0000y

ta~c~ dun !lAG

d[ffi,1(l.C~ t'r'O!11 ~illledi.s·mW !:'!~!"''C

j~l,terl:fl~d~al:C p08itiOir!a~

:~a:redIbet:\vcen tbe'm (2).

~d~1mJlhi~si !)i!l;r(:a-

So,l.ving,~i;le

mecma-

Ilism 'of prmimodi:stal pe:tterllffing may ~,e il.e most: i:mpo.rrtRnt kiCY·~oilm:du(::i:l'Ig the :reg~.'owl:h

754

PERSPECTIVES
]]~nbs,& Kunklr ,(1$' at. st3.te., if we ~nde:r:stDod h,Ow the l~aUe:rn of t;lil,eFe.,geM.el'iil.tionb:1,8i!>tel]i[~ili:s!iiped~ : f~ed, '!&e could engi]~rn' mat 1)<I!littrn:ooro cells. of' :m.mlleg,eJ~eIfatjLl1g <llqDm;dil~s. GlUW'd]~ll)Otmg m:o:]ewk-s could then be, s1!Jppliede",ogenom,I,:y to ~'!m'l[1ifes,ttbe r"I,tt,errlw:i'l~o(Jt: o,tliler inre,T~
VlennoillID.iHowsoan this:mi!ilh~ bepossible, '1i~lic!la1ai"ly i:~llrul]ln.lns. is iinyom!'s: ,g.llCS;s" ooil: of 5reMi.ngly n:ger:tC'mti(D:IlI."def~cie:ITIt

the ad)dhiqn 'Of' nAG H) the repertoire of' neoe..sSElry faeters is 8lmju1pmUHtSl:epb.wmrl.
R!!f~r@nI:~!!
~_p" ElrlIiCk£l. !idrn~ 2" Il!. L"5~.~.mm
1_ iI.. '~llrn ..r, ~"II\i.. G.odmii{,

.'Us, 7~1[ZDo7l"

P. :B" GaM, .,""A Qi'!0'!·GaKil1l" Biol'9'.:ioo lIll'.didJl.!!

3- l M. ,M~~e-II ~" ~vm,:';ljnl:!t, & 3<l{l:1 ,9'%1 U RA. V!li~j.ilV~ NeumbN.!~. 43. J. 1\$0 (~OOQ). s, 1'\\ ij!~b!!'l,P; JjH~.J;flip., .zwl, :;l54. ],65 (I, '!)~O).
4. L 'lj'!\a!1![!,rIc~. .A. MiI!tlliianlll\,

~i!l(ad~lnif; ~re~, ru~eor, ~" ~e;o Md .~ew,'Vort.2006).

6. 11!- UM.llh!~re~'O!. ,D~: Growth [)iff 39. 6..1'1 ~l~?ij" I ..F ..PlI~r:gi!;f,It1W~:htirl~~~Ill..(jru fiI2.. K. ,RlcIMl!t,tIl!!ll'R, i!).?v: l!2,:U5 (190911;). 8. '5,.. M•. MJlI~il: d\1 Si1w, ft. S..G:ns, ,I. P: BirOOk'i!~. Ci!li ,lJ'ey. ~. !l47 (:roO.n. 9., K.litIMl'!lllNi" 1:;.. M. lana"'il, O.e~Smt279!, ~9:l (2,005)' ll(I, C T:dledW. !le~ j,.r~.~IHI.roL1',45 (:2(106.1 :n, R- 11:. ffil!.~. ·~~Di3 4'&. 4J~ {~OOn 1i2. J. P 8~~ i!l ai,.~ie,,(;! 21'~. a:i (l'9gl)_

C [HIEIM IS,TIFIV

FeilflltJl,';~c(md e[~mol1 .Jjryilallog raphy reveals

t~e,Ci~iiflk ~tnjlUuwal d1affiigeHhM !J'nde~lPilii g U ghN.~d.lIJ;:ed i;1i1i ~tllato,..m.l?'ta[ tr,all!§iltionl.

(S'IiH:h 3;[1 <I1ti!.1m[C:pDisli:i,QfIs, IlIs.\NeU as e:lecl:rnl~G or 1n3.gnc;:tic m:.r,m.lgeommls), d:la}]~e-s ar OIlOe:. To S,()J1 o!l1tthe UfIdflrl.y~~lg pbysk~s., mre nm5~ beworkoiJ!: at the spaliialalmd tempo". ral :resQlution ofllille, chiln~~',. which C,1I1l OOC(1111[" ever [e;u;Jgth 'SC!I]c:i:lohfe\W1'l~lgstfml,1's ~ W A.=: I Or-I~ ]1fm}1 lind ~.<Jstm.lillclls a:fe\v fe~:u.to", seeends (l fii ~ lOr~:; sl. Olil rue'7~8 ofilii.s: ~.8~l.IIle.BiJil.nllt Y~Ilg" !lmlid Ze\1!i'ail use ftmltoooc:Oilt[ ~~ed;rol:'! '1I[~~ LOHi:ke ery5l'\'IUogjfj.ph~e: 5;l!IiiJP'shots oftbie e'\iuh;:ing ~tiee stfi!.Cmre in ii. comp~e:.x:il()'lid (lh Fro\l1lllh~ilf dat~> a dei1ir cormoct'iof! CaJ~lbe ~l!LadebeIM;,ccntht: dyl1f(.h~sifa s:~l!llgleelICn1Cll~oflaUic~ S~llll.Cin:y ~1¥Jj o a djn<l~l,gc i!llf;:fectfoO!Yic ~1)1''CliX:!1~. lnreeent Y'Ca:rs"ClOllliP·l,cxl:ronsiliOll-Mc,tal m:ill1es ha.lll\C received \!,fid'e:!!p:re~daltilellHO:I1i~ili!i; part InoHv~t~d by th e q1!lC~:[ ~O' ~,d)cr50ta!nd! high ..:I:e~l:pcratlll:e :lluperoom:!t~c1liVI~l:f .1111 doped! cuprBJ1!es. A~oJilg ~1lneW2!Y. awealtbef :~ew pheOOJ,nCIl3, ha;Y·e' been discovered, i:ncll1d~ng
one pn;ll?~rty

.C

Olnp:Jex

solids with stmliiJ;!:ly' ·(::O,l"l.~il,OI1e~fa<l1l

:re~9Iled ,el'ectlrCWils ,e_~.hibit tm~!s"

s~lid (3), B,eC~iI,t(;elhese:r.e3n-an~me1m!rfi arl\e coo:pel.'a.1i.ve the! wl\io~e si)lid ,M;3JY

'form,EII~:im~~ which .in

micr(l15copk:

()1'l3fn~ \!;lhellill~uBt one: phalonis ahsomed for ,every :moo ".uniitcd]~ .1.~I!~vever,as w'e t:ry~o I.Ill;ck::fstamlt1a.~e be'!.!!'~.M.eril.lg; pile" ]1l;Q]uena, ii, ne>v s.imp~icity leunerg~s 011 the

:~Itwrn,st time scale (.;). The reason is 1:h<ilt

the 11IIpidp~,lmoe:"",dta.tia[l event C!liIill impose eoherence {5}. A cohe~re'1llit CiID1:I~1!eis one where all the fl!Qni:t eells th!lJit fcrro t1u:e~<I,tI:i.ce, e\l'plve, in ~oQbtep w:ut~.1 a ch othe.li".~Jfe(:ting e t.helil:<1lero~c()':lli,c resl)()IDI~e of the sys~enl <'IS 'm~yevolve <\lYllehron~:ii~yfll1dal~,O'i~l1g to us OOfI:d'ic:m i!l!the; tm~e domaa:n. The ul'l:iafiis:t p'~)i~ie$ Oifwriiid!;l]1ll wO;:I;;ide (V02)'i~ a pnM(M:yp]C.1!~ exa~p~~. Th~sreom-

tr.lm!pcra;at~reIDs;,,:da;tor has aJ ~norl(X;lb:lk: ~n~c1tl'r,c, .Pa:ili.~l~.g:Illd U:lt~ngof v~n~dhlilill~[rs .

(,QIh@JWlt

tr·m~rormation

.WIl~dillIllHii'5'iQm~

mOI1l 0.'1 tIiJ@ ffilgillll.iin,r:lllIced {1~ano.grraphk m~n.t i~VOlS~l!Ill1i~',(1by Bi! [JImiJmdi(!!~,-wc;n:~~r~ Atllr}t, lhoe bond be1lw~;e1ii1 pOlirs 01 vafb~diilJlm atoms dlilat~.5

depk~ei!lrrallg~:·

~I()~gone axis (see tI~ fj'§iJn.; top left) is ~t(he hea:r~ ofrhe i~lsl.daling beh3v~or. ..P!a!rt ofthe galle thatlreep!!l t~K':pllin.':dato:m." dose to lOne
a!n(lt'l\1(~[· comes from the [{D~rnru7.J!!tiO]l of two ele'CiInlliiilli on me' v:a~l;s.di;1iUn S[~!~.~millfrom the gai:l1l in e:l;lChml,ge' ene:q;)!, when spins point [11 o]lj)osi.'tte di:rec:;t:ions: .. PJlo1Ge~cit:<uttiOlll, remctve:s mtllraction Ciifljhese eleetenas ;ami s~~g~l!yweakens afraetinn aftliLe bonds-erlOlIJ;g1:i to
1J]l1~

rnph:lly al.orngl CIne axis U.effl. o.n~f

0111 ~(lnger (ptOl1e(.

~iild) ~!'l~sc.ale$ does the :s']fs:temr'fla~ a~Qiilg ~he

~~llilogl~li!i!l d~n.Kttit!n,Ir~IIil~fot~llII~fl~ Wrl1!p~s!S~d ii!

n1:agI1Iet:ic phase letia.g,G'IiI1I~ s!~~UIIlJi~~to i1I slabrn prod L1cllpi1o'lS!e(righiij .. tl:<InsiI::LoJ]]S. co~osS:<Irnnega.tive JiII,l3i.gJlldm,~s:us". k tail~ce"and u evel eI!tfecls <lit interfaces, Thn.s to rui;!lJlmiZie' ~a,1~ir ~lleli:ceneo~.V!{henthis rielmess arises frem pec'ld:i:<IIf physics: of ~ll<lippenS, <I Metal is rOrJiilU.ed. a:ndmagm:!li!C partia[~y tUfted 3d o[ibit1lis.wmlc·l,l d,oil1lThi,llateHle 'll:rlrdIII.g.e:I':I:U::l.ll:slend to Ch'in.1,ge aswell, Nowhe<reis~[s C:!lJm~'l'etitionmnre s:trik~ngt~l<'lin in e.~eotJi"oiEilli!c lind J1I1Iillgl1et'icprop~~ties < ohrnllsi.-

ul1co:~.V'enlJiornm] ,el'ec:ttaolcad

me.

leash a eollective reJ~~1ii(m of ilie :stil:u;::tum] dJ.s;tIOlllOlm, t1. dJelocal:i.LlIti.oJ]], -ofthe ollim,ge. OiIIod
a lass OM llilll,tlgIl1let[c, o:r;(]eilF.Prey~:olJ:s ld:tlr"d,ms:t

hWilrm.etrui

Because [!Ifit1ille~lre;11Iiormo1.a:s ~IilUIttmilr'Cpul,-

cou.pm.a:f1w.

sion, and beCi"lllH,e the)' :tire ta,'l.lppecl by ~l!Iomic' d~MiOtthJIl!s.,tlhc 3d d~itro1!Wsle~d 1:0 I:ocalil:~ Ol!lll thc;~ralls~ri(l!!l·metal site. making 'the S),stCM ~!l&1.d~I~!1g. the; ~1i'I.l(;~~!aa:f\Oltfj3100 teJl!ld to "'{t"t hYbri.($f:q,;!;vil]lI 2p orbit~.~;froi!lii! lhdfox;yge~ nei~hb(]r;s !lind ~J~d over ma:lii!y ]a1!ticesi!:es.
11'11~,aJl.!ithor i~ in 'th~
~h!!,Sil::ldJX.~{.uk

o:p!ical andx..;my s.mdi,~5 showed a rnp[cL noneqll[~~brilllM tf{j)nsit[ol'l~o the:!tIe:t.llll~ic that OCCU.' when the dJem~ityef ,co]m:CIl~c,1:i1l!i!i! pll<l,Se'. '~lcJOmu,lp1nti.cdby 1JiI1J equ<I[[Y rapid reeloctram, is cJrull[l!s,ed by 1;;lwmi0'1d do'pilfilg. ~rr1l!ng.eI:1.1entorllle. atomic stn1c~re (6). '¥Cit. in these stt!dies;, ,omly 11, sili1g[CSIJot [11 t~e diif· S:i!mJliblmiY,. because 'oftlllll im.J?om~~ lof~'\it~1!J(::i~~bo~' ·om~'ud o,\tcilap. gm<rl~ di:;to~i~ns in 'fraellon paJtt:em W~ m(';<'l$l!re,d,givi!'l·S.i~$'l.!,ffiIalti,ee gtt'lDe'l;~OO COWf!Ci'lIlIS{l! ]a!rge ehflll,1eS in e~rI:t ]l1fQr[]mt~onto ehlCi,d.uCUle ci:la!l!;~ ~ti
tH,€:<librllpl[ .eleotroolc
i'lJm:difllagjll'tic

triU:lSiitkli1l3

Dep'arl.m~I1~. ,~f Ph ysia. Oii:r~fi!l tln~l;'~r.~fi~r, Q.rdfi.r.f!' OXl 31i1:LLUilC .E-rnau~:;u·.il1ol'~ln~Ii1L@

C;l(:lctr,O)lic and m~_gi1e~i,cWliOpCf1!i"c~ Will) these ~lO!ls:ide~iioll~inmi~ld, :His C'f!(;Y to 8e~ :h;0\1,~ ~cil~ti()taJ wi~h i~~g)l~ V}l'Vh[d'~IJ'lea1ira~:,§cs the fi.lliil'ilg (1,1' ifferent d orribita]S-CaJn trensform ~Ile:stru.Gtural, ,c:1(:1otRl''01IlIlc. ITlldll'lagne'li:c ~mope:rhe; of a ,coull]ex

at'O~e

stwd~

~b.:~"~M "'--- ,h fl''''t "'--" .~...., ~tI -~ -- d~te:ct ,'" "';h"!Iiii;iO\'-:S .. 'li'ali1i,(i!dh,ul'II (iiQ:ddlC ~Il m,lmb¢r of drl~hlclioll .. spots a't the:sam.c: th1l1,e. T111f: mOistumiPOI:tal:l~:
C~' .. '/.\;\'''''-'''. ~.
'.

"',

In tl'cw~rk

..

....,-~

IPOb]j~~hfldj~ 'dlis ~!);i>~c.~t!lm

"'-"'

ITlifm:matiOil oomes in ~m,dr abi'liUty 10 ~d.efltury

755

PERSPECTIVES
the: fa.stes:t atQm~,c metlons dm:illg [lmi:s dlilnge ,[lCGlU' <I~OJm.g eae pi":lltimlhw asis of d'ne
t]]~t

c<ry!lt<l~. and <IDe relatedto p!81i:rsof'va:mni:i1llln atoms movi:[Iga~%9Ja:tf'n;ym oue ~!lOrtber (see ilih.cfiglll'e, ~il:'fr). 0:l111.y<lt :~a:~erimes do the t

excited o~cany anriS\¥e[pt by the dHfmciiOll probe, Re:noOliOllgl.)O][r1letiy opens Ihe wiily to ['em~rneOOl1:de]OClHlim dilfrnctiol1l ;ilil IHQlSt. rotdk solids, w'itel1f::HIS,p:revi.ou::; experiments per ..
['or,med, illl tram,slmJ:l,l s!<~oJJl.~[e ~1~IIUIt:edo vet)! t Lhlln fi lrns (8. 9~

other CD,)'!irullog~1qlhic p.bn.cc,S eNpaloo; (~e~e rJ~e n~!lIre, right). The tnlll~sfolFm3tir(U'ip!it:l:i'Wi!cy
betweem st1lb.le ~rolanod.in~Cililm:el t:ctrag.o]illl]

ph<l:sesisthen :shm"..~t{)rpa;s:s itlwrougill ~n lILfiSlru·

ble, 'tiCnb'tl!~la1im!lJI,tcen.whil;:h is Cj()Inp:re:;~cd
<ll,QI'lS one ofdle

,11X,es. ne <lilld~Qrnthlmi! eSiab-

~ish

ndi~,:$CtC{)l,ln~c;liglIl bet\\i~1l! l;'h,efemto8eo-

ond di b!!t!o(O!(l!n~,eV- V bO!l'lJdfJ!'l!dthlCl e.qmll.ly

fast rCh:allges ]!;l co:ndu,cmrily tl~f1t' tCOlmIJ measbe ured \V~t~~ rother ui'C11l]l!iquC8 (7), It isil!)!fpres~ivc t~S!t: Bal1.UlI!1flit ~J.~C:hie¥e ~i.s rClllt'()S,'COOlldlThl1le!res(lhl!t~.oiliil lniherrcne(:lion ~modeof di.ftmc~ion. '~cail.lSe IlbiC m,hemnt "'el~~c:il:y ~,i:8]11:11JtC~ be'~~cl' eleenens lind l~hotClIlS'ean, ~n principle H~mlflll:r ut t'liH~ o tUlmlC response mrd h~lld~rDke obse:rV<liI::iimrn, ofth:e Ibmwi!>ecOlrod1a10¥~nent~ of ilieatnms. 'TOthis em:J.the a'l,tUl():rs~gemd.oiUs~Y mted t]le f.h:rnlilof t]ilC op;timl:~PIJ~11,p l]~~se.t'hiU:S InaWMng the p speeds witJrnr\\mi,dl,~.l.e sUlff".reo,ft.Eue' smllpll.eis

1[1 thililk:~lSofllew !ld\frul1~es in sl:toclies of ultD;<I:mst mlCrulTrl.~I, dYllOtm~CSI' a few key onusi'dl. ,mt,1io:n:s ""Orale k>milfbd. ,Elecl:mrl rm~~es C,iWiI, be incorpom:ood in a mkiiQ~()py llppO'lnJillS<, a~ SI!a,OWJ1II pi~viollS~Y by ,Z~iJillHJ cc-werkers 0)•. h~ _iCll).illCIOjfyatw<'!nce is ~lnp(miJ!l1 tor T 'tho Si , ..,~ S~I1i'.>X 00_r~·~l""d·· ~ tr;~~l:ii-tf"'li'I;-, . _.1: ~.l!J ""V_,g_y c ~ ...... <1, ..... __ ~!L~._]...~_ I:rte'~f.!~ o:x.:idie8 di:>.C:tl1OscdhelJ'C. '!.vll'toh ~rekno~"'~l to ~I~b~t impor~mplm:~csel~imtiOtiph~I1!~~'1e.L~;S!t~n.~ ~titediff~ct!.ttto j~~I1ga:le (1 The m;:Xlt fro(fljticr ~""~~~!be ~ ,t.1'I11i1!c·resolution of I 0 fs, er be~m¥~\Wlmichwrurn,] allow t]lc~,uQ\!'e. Inentl;! ~f Ole 11~htC:!1it ato~:s thal[ OOlnl~o.s;e

me'

si:mih]' dm.e :oosJo~lIi1::u·onl> but i1rn so i.r:IIIprO'I'tant speeuescepie capabilities (13)r. Tim cfllpabm~ ity of ~In:errn:g:.lting mHtltC::TW.i~h uU:r.<Jf!ist electmn 3.]1(1 }!;,.rn:ypU~Sle:ili!; opc]fI,ing new hO(f,izons UII!fI'ltcm]ld OU ly be dreamed [I f as reoently as 3J dectade: ago.
t, P.e:l:I!L1T:1, 'Yilmg. .Ii.. ft .~l5Jml[1,~~ nil., 1M (2000). :1. '5., Ko~llil!lii1'li ;!'/(rt., Pliy~ :I!iliI:. 8' 414"43:1 ~:199n .3. K J~i)'<III'O,. i. i<lll.a~.t., 'to TiIlmio~r.t. T0~~ra..Pl'1.I'.!i. 1If~" tell. 7., 4lS? (1997~~ 'I. ~,611d,i~ [),-5, ¥illig, 1(1. ~D'!J!'ImO'll: II. :Bo;lll)~i(••4, H. Zi::~j~5ae~{;g :;I1!;6, 44'S (~O7l • 1:1. PoIIi ~t ai" NtJt. M'atet ~, ,~013 f~J!101l
~~fl:!i~,",(@~

n-s,

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15_A ·CaMan!!lli8tm' ..,.~. flrlN: le1t_!l7,.l3",l,ii'IlH20Dr1l!. 7. c.. t1i:iiilite(, {!I,iy.s;. iIl.lil'~,(t.~t 9, 111~40l. (:2!110l'l. 9 8.. S, WllliarfitiliOflt G,.~~, J. C Mi, 1I. MJi:!i.. 1Ii!~~.~!1'~t!Sa:. 23'64 (1~9l!J4).
9" 18..

s,

s.~nff 30i2.BB2: (2003).

J. StlJ'!i(~"J. fj:, Owrer, It

E, ~lI>IdGf!1\ ~,

l, I), ~iU~r,

m!l!~:yi~~~pm:lUilll'~[W~l!Lllilic: cQi!lJilpm.l.nds n:lJ1l.d liqaidssobe ~reso.lved.Femtaseeond electron di rrw!loHon is evel vi n:g m,f1l1d in ~1~i3!r1d w.i~h K,~:r~y~ec:]!mi!qne:s{.I1)., wldcllrll naJvc devel-

UI, \f,I!.I!.gb!m~·~,!'t.S"!I!il.@~'il.A.H.Z;~lt fif(K.ft/Ir!L MM, Stt I:tSA:1IJI]~,.7~\l!2IJo.S):n,. IE~D9!lliltill, flItmfJS(01~ fhfJ!Yl: ~1It10J) otlIW Colossal ~MtiJj7t.l'i,yml(!i '(~:rlm'~l, i'i!ill1f'1,\ :20012(jr. ][2,. C. ftI~cIIil'l!!l!l'l~ HmWIJ 390.:,~OO UW7,Io,. B" A. 'liiWlILer:i ill m.,. PIlyr, Rt!v. It'lI"'l!~5.,,674Q,5 r(~OO~l. r

oped i.mthe eeeent pmstt wi.thi beth talbletDp ;t'lnotlcce]erntol'"b.fli:>ed tedum;i.qJues. offemi~ng

CHEMISTRY All h~~ catallyn CO~!Jerts; (~H bond s ,to C~H !:lr~~p:o; VI:~ p.~edlkta.~le 5!~I~ctiVi:ty eve:ri,;11 \l'rer~ w

synthetic rreaoC~klllil!lii~l)~he desired products. Actlw~i:ng gllOllpss!lmh a<;:~l~~.]dese1!1lhanceIilillf: re~c~.ivity r()f~:eact~l:lts., ''''herea:> prol.\ectin,g grolMps such as ,amide!> air le:>l:e'[S~oe:k f.e.s!cHvity at :Ill[lde:s]reds~utes" Ol1ipa~e 783 of tll:!s issue, Chen and Whi.te (1) s111:C}wthall !j·1J(;11 lien Wl!tang mind :protechon groiM.ps ,fIIn::: not ah1!1<'liYs liequJrod f!:ve:u inreactieas :ilmlyo.~vi.ng
Cj(JlllJPl!ex.

l' ~ . )]"" II ~g. H1t. s:{llt~c~,!S ~~a~.triiY.' r.'@.!l.a.Y.·.· "C ._.' •. .1. relied he8!vi'ly Oil] 'll.ctiva.t:ing grrOUp$

"

l.!l ~ge l!mo~'~lJlle$,

a~dp:rotootiruggrlf)ups

~O'

slicer

ti:va:I)cdre~ta~l w~th ·fI. sekc~Mt)' ilalt c<'m'100: n~ned byclliloiclf;; olf cll!ta!l~:st .hi! prattlOt:::. ~H)WC'I~r, l.te O'lfC ~m ilr fr!OOilil the ~al p~rl:k'iJ.I:ID'!ty V
~)lr110l1theSil~bstrmJt:e ill) a: oomplJe.1i( o:rg:rnl'ic mele00.1.::: with 'Il1~tu~tiplefuflctiiOll3,lgrn1!.lPs. Ptdla~~ tiJ.~cgl'e~te[iltchallc~ is. fi~dillg cal~lyststh~lt: se]ectriv:e'~y Blttack C-hlbondi('i.

v",hi~l~ :@~·~.1ibiqui'~m",'lin C!rg{!!!l.l~omp@unds c

but O\1irrL;: ofl:en veil)' ],Q:IlrlCaCru,,'(:, A l'lJum~>C1: Qf . 'I., jl'.~" " • '" cata!J S(S, :f!~.~''k ilo\1i'n!ulOf!!!HS "C' r~1 acU\<a~!O~l '.-~ I:,ea;cri.oll(.n, bl.it~lCy ac;t oml)' 00 g:~mpkmolec~,es such !liS hydIiOCI~1rbmu., ]:t1J ~n(lilecOl~~lplex
i)~llic

moIClCU]~j

~UC~l ""''''those (lOI~l.Dn]y

elJil!coUIW~t}red in p~lIu:m,S!ceultuc;8i]S:,.numerous oxyg.e1~ er n~h1)gen-co:ma:ilroling flJniCt~onal glFOtliPsare dis!t:Jr.~IJI.~;~ed overa core heldte-

molecules.
0'

With tline rise i(lfg;feClllc~~el1l:isny (2), urere attelmitionis beml1gpaid to d,hni~marililg m;tiiiwtt~ ~iI:1!giind tproteotiung £l.lJl..lp5,.,melcv-er IlossiMe"
fOlf tW(IIiCt1S0il1!.S •. .First,

54!lJ'Q.

they

gene,t"d.re\\'1'Is,re.,

Seoollid, bott! <!JClivliitililil:'; I1rdprowctmg group:s ru!l]~l]reo>.mI sy~.lthe~~!\; Sf,cpS to 00 inWM.Mlood

poJyfil:nc'limulJl.mo,l.ecul.es(see the f1gl.lrei"ar

gethel" byca:rl)ml~e~I'bon bends, In S;ltCilml II polyfm.lclwlIThlll DlO]ccule .. mlSe.lec:~.w ..tim::], at <I:Jii1IYoilia IffiumJOOt ofe-~I. bmds Cillill [\esu~~ ill a cockt:l]] offi:nal pmci:l]cts .. Chen ~m:i,W'h~te IUlW repoli a strildl,lg c(Jil..1lrlt:er-ex~nl'ple thal s:i1:owflliu,ow rG-H bOllJds Cain be <],cri,j<l.t'oo se]e:etlirvcliyeven m. complex

1l1!U;~:l'\,~!Ml:p~:c'r, iiuthors lI~ed ,a~ ]rotmJ c.o1l!rn]}'S:1 Tile S;e~f(.tive (1J!lIiIi!ierrS~onlI'i1Ie iI~~~ma~3I1ia:l •. coonlpo!llnd i!l1'I~reflc:t~~lts~protecHng gr(l'II1J)S :al,so f1Cl!)d to COl:ll\'erl: $peci.fic C-H bOrldsilm,a ,'WIidc\l~Mtril :ste:p:;;.N:. be removcd ~fter l!e.!!ction. ,nl)~misin]Dl (It,ft) lS,e~"IJillded fnliliJl i ~hrll!b u~d ei~ ('Ijfnno]~eules to,C-OI~groups; th~ bC:riigJli) ~fi1 IheiliiJ;cll ~'cmll if! (tI~ f1fl'S'e tra diliol1a'l mEliJ:lkin!~. C!'ltal:y~is:C:!11giv~oollcti;v:ilJ :mind se;llCctivily ~li!Id~~IIiH~~lSi~1t"i ~~ydrog~~~peml'ciid(l Sii;';i'i,~C:::;, tliS Al!h.oIl9hlalf1temi~illl 1iti3!~ filUlifllemi!l~ (-\HI b~Mildsai'ld without the 'ri~odfor ~ct'wa:tmgor protcetin,g thctil~ii:rii!lc ~~~ rflft~~e o~q;bllC~li.iOOm. (i dcilic:~t.e ifi'li',ro:(iid~~lu!li;;ti~.!iI;:!il.glrtil!jp.i~. g~,ve~~ s1 r'lg~li g_oolt!PSl.1"JoC kkil ~.~i~Yi5treal(,':ls wifh tull1l1ac[)e:relJild~ng O!'l d1e.~ecifl,c ca~~t:l\t.e ~~t~l1l prociluct bii~lwt~whrirl tlhl~ Chen-White (oltllly:st'is 'lsc~ib>c the~m~r~f!!bly hig!l~:'l~lcc~ivityt:Q' a l!h5edi n (Ofil;~l!Iil1Cti on 'wiillh hydlnog@11i IpeiJlOllde. flil~s co:mblilath;p:n of a l:iI~mbe.1 o:f ~uscs. These: ~!'1Il;p~i0$Ih~Hh:!l (ati!~t Ii!.l!s,h~~h~~l~(tivlty12Wnl"f Tille aJ!j~h~r h fn the lLhe'i!"acr~IlIl'~:rJIlOf Cillelil)~$lty, Ya Le illclude I'lliC re·:;J!c1ive C-li bcmdl !bdng 'ehher .. mmp!e:l!; mO~etllltl;l" but poo,di.ctab~~itll' ~or other Unl\i1~f~nry. UW>I.Hilvm, a 065,2(1, ljlSA. E·III!.alil.: ~ ~.Il~lCrelldy ore: ~"eii:lctive~hailla)my(nher. 01: m (i!li~e's i~ ~eCll!Jirrre detaiileod 'Stlldy .. w IrIiiCI~eo UillbLJ~:@Wi!I~,I!W .

PERSPECTIVES
phys~h;aIJy ac::oess1blc todlf: c;aitalyst,. TIlc can i'l15>O be f1tlllltacted to a spedfl:c"iDcml .• tinn by b:indliillg flO ,a. prej"o;::ist~ngf.lmtti{)lIil,d grol.lpqdtmnthe [·emc1mIl~.,tjlmsm:tacldllg owy 11 :m,eamy f:-H bead..Agorn in the ;8Il)eais to 1J.tnders'i:al.ldthe re;le'WiJrn~ lek~]vit)1lrends:frOO1 ~ '!~,e :PJle:vions resu~:ts,iml ordeil'" t:o predid tJlne 'Ollt~ come ]~l":lII,Y slrhseqoom: case. P~,-eidict<ibili~y is e~,sellti~fbdhe desIgn, 'Of<liiFIlLu~,ti5ltep syfithe'tic wlde relying O\fi,l, ~e~ecit~\fie. ]~.ro-stlIg.(l C-~-I
.Ol'e
C!lihll[Yst

.amiwtrn(ll1l, bCC3lU$efai.I~11I:'c <It BJ Imlter stcp \l;\L)U,]d Vimre:ihe: e:l1Jtlre'sebeme, This mluu:k::lb~e'~i'ofk 'is part of an cmeng.. iug tJ1eJ1d,in ,""hiebd:iflerml~:S ofsclecl:i'r'lc, ,[;atll]yti!c C-l!l. aJetrvm:ion lC(!acihons ~[1e berullg .slllccie~sru:lly 3;pipliiedw 1fI,1IJ001iC oOIlWillex mole,oldes t.\\iaililpMrK:n:IS~,yea~,YiS<lged ( ~6). Wiih the ,oo\ncep:t1i.~:111 bm"l1iel: breached fOTIWdJiO"\yb.rI:i!OJl .• ~brther ~:mriklil1g .. ~p~iC;i,tioo:sh')' W:illlllJm M;6]e·· cules ~j:\elikely to em~e; in :OOfi!l&mre.

1. M.S. (bill", r.t C WIl'ile, 5(i~(E'll~,]a3 (~O[)'L 2. ,P.T..1'!IrI·~!5til~,iii" til. KrlF!1~,liIOO'r. ('~ (/j1o'm. ~,a 6M ~ :n.
'~2(00).,

R:~!l:!i"~!W!l$:

3.,

'(ii" ~~e!.

Ed."H'MJ'tll.'IlIrJk

aj(-HrmntJirllln(,!rjQl\l·~Mil:e,...

V(H, Wein,heilTl,ll'lQ~l 4. 11,_ R.ll)id:,M. 5.s;ankiro" r~'~;!i1i,;!439 ~:2~O~'_ 5,. ~~. fj;j~, c. O. IrlfiiMH" l~. (~,!lbtF!f.!.,. G. 'IN. 9:mIMg. Ill•. S(j"t\ill't! 3:12.1L 9!11't20M)"

i. ',,)I;. ~b~nget

J. IE. ~r~ilil'I, l'hIfli'fJ1417',:5:00~2a02'.

too

SVS-TEMS

BIOLOGY"

Th Ii:! heart of dn:adila Iiltimelrte'~~1iI 9 in !rYan lliib3cterii3i iis a.'toggte ~lftIn.td11~hi3t !l:on~U()ls: th e pE!rkll:ih; phil s:phoryi.a'tiO:!Il fl'f i31lkey drmi:tl!lofote'in.

T'"" Y"'" 'Il",

-

on ~:i.e scales of :5elcolmJds Pl11lifi,ed. proteins WC\OO mixed :ilill, ;EI. testtube, ol'ln~~,lllti:e~--;andso seeUlIJ1. dn.ey s[pOJltmlGOIUSLy .ge'DiIJ:]jlli~ed $~~st,rnnedosci~~ pom:~y :suhed for S[i()W KaJiC 'CO:JJi~J:I[ex. prevents ,KaJ~ fooMl;u aoovaiing K:.1LC natiiOJi1llsi:lillhepho~p'I:IOFY1<JJtID]ll,:H'<J:ie' arone of ,c]!icadinn ~lyl:lrums .. Bm1m1 : fh.e pl'Otei.m ,[I). The tmmee ffililUtehil's-KaiA. srtrdies emmiJ,1IC detai Is OrST pbosphoryladolL Thus, 5: T KaiB. aindK.aiiC-i~-;ere p:[eJ!,fiousiy identified when S~K~iC !l:0J1CICl,1,lrn~ the- timing o:fKai!C p.ho!>~ iis;impOilllOlJlt fOJ the daily plllrerns of act·Uvi.ty phorylall:io!l1 dJl~ring oscilri.o'li1 is h~glill,KaiA is sebli!iQiIliS;. !l<3i.C is, phoSIJhO" lind behav~or ('circa:d~n rhy;tmims} ~in the ,qllcstered by S"KiiI~C "]Ildi C:cY'llliob~c:teTi1!.mli Syru!ciJococau.s e,{rmgate.s. ryl med <Wt tWlJ sites and 1111 Kai.:S, ,and K<l.iC d.~plmi!'l<'II prurticlll.ar oooer.: fum (ffiJ phory~!ltiOJ.1 predomi!lill~; A~mniishi:Q~1y. o:i!cllli1ti.QI~'ill ofrrn:oopho\~fl,tioo 'fuJthereeo~stitntllid ~y!l.t~m were simi1ar ti.) .aJ t~lroon]i'iC .j:,e8i.dl'!c·,theimJ \iih~!:"!S-KaiC ,eOweeil!tr,~ti(J!l] is ] cl'I'!', KalA is t,etU1CbilC:1i6rhim.·~ t1ii,t1JJ.fil.ldiitC~d.]~nrhyt:I\Lm of ,0'11a ~tt~~.le. S1!!I.bseq1m,elJ1:d.y. ;!boot2l!hou~. M()~(lr.ml!i!:m!ti()Migl one gf the U®t)~rilfgemHl tll(\!)sc:r~,~5l~-d!i~d Ki,iC phQspl1Qryla,·th~!li~~t!.~tcd. the prole~$. Kai.C, ~~m: ~ng,elhe '(i:i~,f~d:~~l 1:1'1(; re d~iliaJo~rn'hol}'!a;lcdi c ~ pcr[od in vivo had IllCflr~y i-de:llJjtical e:ifeds ~:Ul and thl(lKaiC reruens to l'til)ugh Il1(lCbUJlgstudlli!'~ .~yaf:tl!lbt3«~'rci~ll cfiir,[adlm;J~ du(k. ic;f'l~Rust ,el' ~l. ShQ1.iV th~t VilfO. T.lrulu~~ relatu!{'e:~y simp:le :aJud big~ly a an lU'!$f)oo~phory~a:too s.rnte (,dill: plii'~fll1oryla~on .aflddllphosp;h(l~I,- tile st:oi(;'~,iome!l:rilo ~n~mi.bi~ I:(lillmsitimekeeper s;cem:cd~o set t~c p.a!ccl~r '(:>.CiC the !l1gurc).The KfI]A ,a.t:iono~tlile dock Il'mt!1!'in IKaK On5e!rIiJ1le tion of K3)lA by S,.,K~]C pl'meill ~-eg,u1@!tes~.1Cseln·:mthi~colD'll:lCi1red orgaruusm, '[he b:lgrenm~lli:Ulg ,alf'l!1Mim~olililile b.eJ!:a.I'IlIil'Ji ,rn:rutatory c:haUcllglCwu ~l:l' dcle'rmil1!i,C howth~s; dook ~~i!'km:s IPlDlno~in:g: ,~w.'O~ ~ allows the: cydk;pllo~lh rough';;)1 doulll~e-ne!ilf!tille·fe;~dlbiN::~ ~OifJlJl phO!l!p~m.aryhlll;jj(l]ml and inworks, 'TXl!ffl stud:ues" rc:ported Iby the K('m;do ph.ory.~$tian-de,hos:phoh:edl~ tllrii'lJiI.tOglgles loet.lfIleeln t.WO states hib]rt~~~;g a!ruwd,eJlhO\llI~11:O~ ~th: Ihigll,()r ~.D" CO!IiIi:!E:i'lU,at'l(lfll ~r Ilre~ 1),I'<I.tIOI) s.ystem.to iheDome gml~')(2) 1[11£1 .R:l1st t!l ai.. Olrn.p~ge 809 ofjihis by Uss,rce, ,(3},no\1!!'pliD¥~de...Siltis~f,yil1ig anS'!,'vcrto rylatian ~y K<liC. Kt!iA prot~!,Jil. tli:.illl:l!. is thii! tl1ird Pn1lt)~l'Jil ~! mil,oso~]~at!ar: This ]~m.ii1i.b~tUOll, eleses BJ. feedhack ~oop tlruis '!lne:stUor.Ji.The osciUrut[m~sarise :fmm Ule .BntB cycle ef IP:hos- Ih~ o5dUa~or" s.~0\v.,OI.·derly additton <lind ilie!l1i, smmtl<i.diio!l1l1 of' piloryla6o]1Js <1100: d~p:hos~ <I:nd.m:akesK .a~ <lind A two' pho:flJlha~es {r'Qm ;bIle KaI.C protein 'Ihis phoryla:tiol1s 'I/¥Oiuh1. liIIot necessarily be- e'X~ S~ Ka,i:C mu!~lI;ny 1I]i1t<I;golJist~c.;. K,t1itA.is II,n~~ 1)["Qvides a fa:sci:nating, ,e*'llinple of re<illm::4D.ol.li&- pected to ~ellel7illte oso]llilit[olm's. COililsidl'er. fOT ative regllJ.I<JIlOl~ OfS~K.:l]C.because ~t pushes ,example, t1.c:;tiv<I,ti.on ,[Uuillin<l.ctivII.tion of the th.e b<l]ance Ibetwec-1:I S~.l:tll]C <JJnd ST':'Ka~C ti.e ~SileJ:l,U! bi.o~,oID'. her-e Ul!C lI:bli~~ty w topid:. apart n ocmm.plex systemliil has, yi:eld'ecl iUl,ml.deJi'" e~.lzyI.ue .Ea:k2 (e~tl:il'celhaJ,iliJj s~£_['I<lI~.-;re!lUl<a:ted. (P~.lOSliJihoryl1Jt:ed On se[j~ne lind tbrooni:Jil.e) ptoteiJ!!li kinase 2). like K.<1IiC, El'ik2 c;ycies. to.ward itl:IDelaliter. COJil,ve~ely, S-KaiC ~s <I. neg~.md~g of haw the ""'i.~liWl~; systeJTI."wrkJil. The; am!]tocm Imdrell1.1ml<J.1l of pilimsph <1!te; can iliITlolJigfollir ehemical stRitc-s. mJ:oditi.ed by ative[ie~')!lil at.or ,af K..'1I]l\, because it seqaesters <BJ:terii:liplDrein'8: fi.Ux:ti,Ofi, m.l,diflhep~'meinis e~lZy['!J1CEi1m~tph()spl!Jory]iUe:"'tyroiSmc t ms;Killllc K..tI~A (winl the liu.e]pO'f.K.1IiB). This mUllllii:lil, part of ,000!1C'hlliOfli:. o:filrlool'llC!ting fllC!tons;, l~ 1ih(;Il.aI t1WeofJiioo (4),. and ti'Klill by CliH,)'ITlCS <It:lJtagolWis:1fl!II,, or doliblC'-fl,oyvrive·R;od:lDack jjlllt)~hory[a:~,on status;ma)lrday i~~brmf~tion th~td1c~:ho~phoW}'l:.1ito ty!iO(l,il'J;c :tlrst ~m! th,C~l ]001' (sec the fi:gMreh allOlivs S-KaJCa!'ll(] Kr!iA nJ.e;threoll,]I1JCl (5). B'l,U'dlcre iilllmO ~~int ~lmt'&Iis rorul"lct~o:n a~ 01li bistlllDl,~rngg~,a switch \!.~in'l tI~atimp]I1'IlC~ (Jll somlli ceU b~]'g'O'!!vior:The dynami,c8 of reve~ib]e p:ho~pha:t:c~d.dJi'tk'l~l ~YliU;'fili(.'j~'Cinal!e8. W~a~,thCi~'keeps :tlin,e ~dk. two ~J1ICrJ"i!i.iil:ivt; :m.!bl!t;ste~d;r-~t!it~il; (lISe iII~phQ~pl.~Qryl'~ltuQ~ !,llnd dc:ph(l~ph()!rylflINa~ (Yf ~:UQ~scot~ldthe':i1J~ri~er:h?~ tl~ s®c~s:~"Ve nipK!li(: f~~msc:tlHngi~ro 11 ~~a~i>cs~~ai(jly-~'~~te piw,g o:f the K~iNS-K.1!iC ~w:i,t~h b'~lt\l,"e!:'r! 'lliile ~Y~i'lors.a Fe ~n ,he D'g,p~Ft!'li!emt ~r CD~efi!'llC'.al I'!dl ,fI~ld! a1.10\'\i'S..iI to 'QSl(l~lki!te? ~ thes;e t\'VQ :::i~:~~, Sbrting w~t1m! 'tmlO:hospllQ.yf:)r-:~tl1S IBiolIl'!JY,S~anf,ord IUlnlll!ef~jry S;ch,oo~ of li\$dic~n~. 'Th.e key insight:wlisthe db;corvcry by Rfuls,t at:edKaiC a:nd ~he:KaiA/S·KaiC swhol~ III its ~J:jI;;IRI!lr'fl',C1L'9Il,:!:05-5.1"<II, USIi. E~ITIUil~ iilm~s_t~rni!il.l@t :~ilnJllrd.@du ,(3{ al that the ser.ine:-.phosphOlryl.atfldrol"1Il1 of ~ow-S"K!I:~C COIllNm.tra!llOlm. iim~e, ph()lSpiin()l.y~

s:l'n.owed thaI wJm,en a p]m.o~pla.lesOlJree . (ad!eIlQl);ilill.e 5·';I:n.iphosrpha'l"i)rn1d~hme

Thka. RD.,",;' ~"'"P

,and

re'lll.iil:()VS!~

in eells are

US;!!.HI~]y .f.'llpid:-occurdng

~iC (S':K~iC)b]~~dlt; sllo1t~,i.ometricnUyto both Kai.A aJlld KaiB. nne forI.lliilillOll, onheKaiI'\~:K;ft]J3-

en

aoo

PERSPECTIVES
l~tion '1!1']]] p:~do:n1fm.i:llB.re. and JilJ.1QI1C and ~uo:re ST;'.KaiC will build l]p. As tMcooCCIlIJrnalion of S'f·.KaiC increases, S..Ka~C will. increase too, The inCle'BJsin!,'l S~KaieC will sequester ~uore and Jiilll:cme fliiA, whichi~cl:eases, K tliLe rate of ro:fI11aJtJUOlJl, ofS-'K~iC This then c:~lJfije~s~no:re ~qjlle.stliatiIOJl ofK1liA.lll:lcll W 0[1. Eve:rllll!lIl,y dep]inoS;pllO\I}iI.atOC:in cliomill:llWS. 1I1i1d tliLe,sy!i,tem ~ cifive;l!il back tll Uil1[lOOSplU)~,'U:edKii:i!C. decreases the rale af1hnl1i!:Hon o:fS·K;aiiC. Thas, the ciraadifl:l1l 'as!c]~rn!l!:or SYS'IDlll ean be.thollltg~lt of as a bistable sw,iu:h. toggied first by' the, slow <liC-CIJ]Thll1~!fliOll of S,KillC and. tliIen by asl.mv ne:,gm:ive.-feed,buckl!oop, n:i:s~pe of 'CiJrClliitcml o~cilbu:e, <IS Rmrt etai. d.cmolDUstmte through !l.siDp]e diflerenlti~;)] ,eq;l]ilil:ioflITlOdel whose POUJlJiJm:iMeTs ;iibreoom.trtl~l1tlld by their ,e.'Il;perime"i1~<'I1 ab~~Jtioos" At first gblil"lOc,t]:lC' ckc~d~iin o~ciIlOlt~t ,eyk~es d]oos nat seem to 'i'i'1)~ill the same
\l!o1l,y.

cseillame
ll.

Illi!JjY be. qnhe :sbnihu. .lBo~b dl'Cl!!tH[';; ;in{l~lId.e doub~e-Tleg!lrri""e~teedbad, ]oops; that might fimctien HIS bi:stabl'e triggers, uno II)Qtl:l ~Ildmle siownegRltnv,e;..feedbiack [oo[ps. (8). ]n teaas of sys:l:em!>~level 1!O!il:~c, these oscillatm"S lIpl!leall"ll~~ior:e sl,mihlwthan d:ifterelJlt. M<lybe th~jS: is how <I. suecessfnl CilrC~d~l1n

Iiru~!>ffii

be"i[milt

What, tI~Jl!"f1Iip8 &e K~WS-Ka:~C s\<vitch bflckto release KllIiA1H'IJdi fa,'\c-ot p]wosphorylll· tii(lin~~'With ,1:(;!!iiA~'C(I!!UiesteRl-d, ~S,·KaiCtbn!II~1!f· tioililCaIl!r!o,t be m<li~U!]~~d ind(lfi]!!Jilr;::~y;!he ~~e ofS:-I{.,!~C "mCluctkll1llromi~i111MllCdl~Ut
prcClil!r~r
ST·:}(fliC

o:r

It i~ooni!p(l~ mainly IQf~.·":!1l~riptiomd

wiH e\~fhlluaJ!y s:~o"'\1 ti.kf"A~

as, ST-l(aiiC

bCClO!l1{lS

d!cpk:u:d. This elect is

t~lC eqrtli\!'al,(:~llt of a g]ol!!l!I' negfljt~,~c-lic~C1back ~(l>IJp--;all.~~l.{mea:sen S~KHiC oouoentmtiorl i decre,!Ii~es: the 3:mou~u. ~f S'f-K.ai.Ct\wlmich

rc£iuJ~h~:i8iJ!wj dirlect~d pooitein deg!'fldii1!tio!1 '(,6). rotherlh(!11 a st:ok:tli@n.lewu~a~ly .~:on!tmilled f!il!,tophl)~ph(lryl!Mtnl:li.,g M(;r!"M~tll¢tFi~hospha,· tase ~~k~KaiC andm:l!mJe of th~ c!.!k~ryotlc Icompolmen~ ~:1iS,~ a~y seqtie:~ce: haMo~oJJY h) KalA ,K!BiBo'I" Kaie On the Qthe:r :~31ndo the dej!l~,princiiPl'es of the ~.\w ~sc~:~~s:ton"

U. IM~k.l~IIm:ll!iI al .• ~frn~ ."Ios. AM (2100$). :2. lINI~hMi1!t1!1I .at, £MBG,}: 216,·~'02<) (20017). 3.. M,~. Irlu~ ~,S. i~ilI"k!;oill. W, S. bme, (I,. S. f[,sl~r. E,. ~~ O'SMiI, .~d8'll>f 318. 8<09 ~2,D(l7.I.:'Iptlblhlled oolijmre<l O,wbe<r :21007WU12~ e!'!!le',:114a~61. /l, ]lIE. Fefr~l~r~ Ill: 'R. Elhat!, J. &101~ (heJJi, 272;. ·:Il'.Hloa U1lW). $. if, t~o, z. 'Ii, ~~mg.J l#¢.r:/l~j, <l76,,3~a;! (10100.). 6 •. ~;, ,III.. 9!~~nl" O.iR.!I'i'e!!J@r,.Wt.l1ure !lIB, ~:~ (2000~.

IR@f!i!irell(~"

PIHYSIICS EJiIP e'(~me;nts: 's.n ow ~~at 'ete CWlliI :5 pin:l; CiI!rl ffilowwntih,olfll aissi pati oni n a n:O'!.l'el elecm(.I!'~
]1lj;1II

lil1!or.

di:rocte.c1 by llppl.iJed'e~eetric <'lind mg'· l"Ietie fie'I&. In rueenf y,~rg, r,eMl<1i[iCher~ ill. Ow rol.iiti¥eDy ),Ol!Ulgfield of siPintroillc:s, ha,;,re ~[I)l'Qrod thi8 ~I'~'t For LIP'p~icm:ioo8 i!) mic~ dCc:tfO!l~Cl> [H;:Yi.~din 0)1. The gQf!~is h~' oon'lTI::!;1 :rJ!lld1i.lse s~i.ns l1iI!IIuch ~slloday's ~ntCi· gr~ted d!lc y~ts U&'e the pro;perty of IC~~I)(:tric oha:rgcl;or c{ln,.pt'~ling nper'<!li.olls" 011 pag.c
1'66oH~i" isslUe,KEillThig, (H ('d.(2}repOrl: e'Xllc:r:· iMe~l:t'.'!!~r'estiMsthat :shl)\¥ ~~~eexi!1it:ence ef a ~.e'!.~s:lalte Of~Il31tte:r thrilltlli'J!ay' ta}:;:e SpilmL1:mn~c.fi evenmniruer. Not onl)' does this wmk ofrm:" IJS a leek <lit flmdamelllltflm]y ~,ew IIt'I:i)!1'Iica:~phe.,"
rlmUe1I:l3:=

E.

mel these

~c.ru ...'O'.].m.'.s. ha.,ve. .: ....IH'(),p~'4lIy.,..•... k[J.

S]lIl1:~ can

be' contrclled and

iPJ.

m'-'IlIM.,.S .. ,.'Jl' .•

m1Jd! lsein Ifll!et.Uic systems a . (8~ I 0).. ~I.m.'e!;'e:r"~.he detailed mechanism ill these cases ~tfu~W !lood~ uJibc ~CfMtintl.ed; ~lt!;e

nol,v of ch~.itgescalj:Jst~U be

d~S'~ortGdby impu.vity :-JC~U~:!lfi,g :(1Jf!d tb~8 contribute tCl

the sp:in cW'~nt 'fhe:n;:fom, .~l,I(: need t:o obtai!mJ dC'~~: obscrva;tkmsof a tru~y d~~:dpatioll~ niS5~pa.'Ii'0l11:ess :ll!m:\I'i~ klllm.VIl in the convcn~liO]J1N;I~ si!lml:l~eil1lld~oo~i!lrnrbil5, ~4}rm]~!l!il Iflel. flow o~ IChalrgle< <3nl'urn:d title qmmtmll~. llmU e;ffeJ()~\1!'hel1e 'I1\r,e boolnd:~ry ~d llIifahlili~L. Nr!!! ~g"'iI~tt:: l1ie~d i$ liIeedec,. 1iIQ'WeJ;',~r,in tine ,e]e;CltiJ'OJIlS dehLecredl into ,ci;m;. me U')~qlJ!.~!lI!l!.!rnspin HaiU syrt~m hi !lhn,ifm~if(l spin"1Jp @!1Jd s~l!l!"dowlil cular paths by S! nl<l.gneliic€ield (iillr,OOrrs!l.ew in o~p'l)Sioo dnctiO:I'I5: in ~dge d'lallli1~~. ~tate~. 'tsee the I!et[ p1l1me.]OfUUl tlg;lt~), app~ied.el.ectcicr.~M. 1],lC spurn, n,al.~::Jf:ect'iV<lS Tirismetierris notmlldom iI,m,ong eleettens : bl!~tis ,coheren.t'1y ~8iI.lj.:mcl, lead:ing 10 01,llO~.]ec:~ ( pl:'o;!}o$ed trrrleoR':1I:caJily]0. alio based. Orla]]1 ti",e stil.~e.,11tl:ilsffilteis st ..ble becll.use anl;lile "'e~tJrillils:ic'·~11e.clliu1ism(3)\, ~nwm.cml hnplL'l;it~es a:rnownt ()If'~JJle~{the M~garp )is mquimd in n m1:lreui~.I efied tke ~iPirl't~pand s~in-dowJiil\ d to dismrb it Ina re<li[::l'iIImpl.e. the eleetrans ClecwiIDI!il, ilfil 'iJPpo$:ite\\.a)f8 •. Howe'lrer,,[ece'lrill inKme.st h1JiScentered on 1IliIIintrinsicfiam Qf IJrnulce, b<1lckmm, dleedges. c~ms:illg.1:I, :net (Hme·~ dim~$I(I;rnd n'l,Ot!Orn:li. whi.c;hcorrespond!l ttl' til sp~n ~bdl e:ifecl <lnd the -P0iSSibility of 5-pmlmv ng~1!" olf Cl.iF["C!ilil aroll!!-d ·ihe: ,ed~e.Bocau~ '!hf.i 'lj!,,;Ih~t energy di~si~~ui(ln.. diJICcHon cf'mts mm·tof'!i8~le-W~!i U c:!'!~mot ~~s!(;adof ]~l'Ptlrirics.'dlC iI:'uri!ls~c: mcoha"'.".N""'·r"· ~'d' <;:)~t::!\,1;lIa.~ c.!.!!, ~O ..... U!~"'.p<J_O .. 'tdsm -rdie:s 01"1 theil!lit~rpl ay of th(ls:pin;'!l1d 11:1" ~e..... re .. ~. ~'I•.·.~ I'lil ':Jill_I ~ . '11- ,~lis"Y",tI' I'll " o~biM& m()!liIOt'iof'!h~ electr,o!lS ~!1 perli'eC:1 o:fthe HQ!.\i''of charge i~ 'th,c. !l;upP'!i'C~cd in the ,qu~lperiodic b~cli:gmt:lnd ofihe !(;ryst1l1 ]a;uice., ti.unl"Jail ~stem .. A ,;;rudal q1@esti,o!l i~ whe1:~era ~:i~ii~r ~ood:WIlg ro d~I::"fu:ret!tpf!tl~~f'Of 'the up a:llid dQW~' s;pins.. TheilieQrcl1i~'~ P.llOpQis;ilI.~ illlis c:fffi'ec;t shll:eis po.ssib!e for ilinlC spin ~Uru:C":OIt.. .)' (lO~fur M (4. j}werel"ollowOO. [by !.I'n.eexl'eoriln{:lltal :l:l]s- leag:1Ji.L'.:s(md 1 sbdied th~s qtlesU011l theOl:et'i~ 'covery ofd:m slPin HJ]~ eWec~ in G<lAs (6, n c!I]ly Ilrl, 2004 (1 aml\:ve oorl~dered the s~~ln applied to
OCCI!IT
l ~I

Sipil'llli:Onnot

q,lI{! IlIIIUin1iH<llll sy~,ti~ml ([,e!fU, Ilh~ Ng lileIl: ft)~ldC<lLlseS. lectrolll:5 to bOUlnCi~'(!fl1Iilre eeiQl12 01' the e

1111~~ {OmreMi:Mtal t

less spin currem;

km!lY

also aUOW' Ilh.ede'l!'e]opme:l1lt

of

:mO'!l\e] SJ~iil:l",(m:i.cs de1Viioes.

M <!]iJyre.se,uchen have el'lLpl,O)ied.the ~ called spi~1 ~,"I e:ft~e!i:t.<Iili a pOSlsibl!e reutetn a :~;~Plinlil,'Ulllliic ,1Lp:p:ticar!:~oTl:s.l',h£:' OJi'~inill ,1-IDa]]e:l'1eol goe.s;,baoek to the .liu'e ~800s"wiruell I&hvin lilllU ]iJoticc;ddmt ti'll'olmgc i!.voutdfooo pe~ndjoo· 11'111)' 1D a curreat flowil1\!:'; :iill. :Ill c.uoo]!q;coowiIDI a l!1I~<'lg'[l!cticfidd" [li1L the ~~llJ!iihlilnH,lll effec~~s. which '!Ve'Pll di¥OO\~~OOih! time [980 ,M-d 19B2. cj:c,cIWtC~ c~m:lIl~ct~m::e t!!lre~on ~1u;;rrvtiJ~ val1!!.e:s.ili1dle SP~!l HaUeffoc:t:,dle d{roctio:n of '~en{W!,¥ OfellCCbJOlli; ,ean be eaillJij',d1Icd, depend· ing. Q:!1Iw!a\::!:her the ~p"i!lig iU;por d(lW~I,. by ·all

,me

i~illlllil'~ O'~pO!lrtl'!l~.llIt of .ApplEedl Pi'lys:lu, IJl'lltloi'~nit.!fIIf Tll,ky.o,. "!Iliky.o 1113·:eoi5~, Ji!pe.nl,. [-milil::' l1i1!g!ilOS1!@ilppi.u'tmkya~1!c·ip .
The ;lIu~l!Icr

n,

:2 NOVE.MBER2Q07 VOl318

Selll~NC~ WW'W;.soier'lC€lmQlg.org

PERSPECTIVES
Hall co]~.cl\lctiv~ly~b:r a band ins~]lato:rw:it~m..<1 rnuite bflludgilP caused by tUle spi:~,~rbut:illlle]T!o ~ciIJl(m.hil this ease, tte, e~iC~rmilS 00\,(::' <llve:.loo~ ity t]·ans·ven.e 10 ~Jine xtemal eleetrie field and e <Ii d~~:e:ct~(ln de,ends. on the ~p[n..ThlllltES. that Illite :spin eurrentsin the tDl,dly oCOJ[pi,ed bands do not cancel. el.tc:l.l etlter onto and. flinitEl $p~n Hall cO[ldllJ,eti:\1]t)lliC:im]ts even in the blind i iifiSlIll1iIItot. Thi s :rt;li;te\~s called 11 Sp.Ull ll.lI~] iJ!i!:lul,'litQl" and ti'lrf~ cmll;dl~d<vte:mfrterial~ we pmpased illdm1Jed~lg:re. HgSe, HgS., .. PbTe,. PfbSc, •• md ,PfbS.. HQ\!fC'\I'e~:.;t\'4~ !:lot deliroo'lil i :!(lfilroo:t!!me:r!tfiUy di8ti!)guis:~ thesematerials I:h:lm~hc!J."lU ~dbarld! ru~l!si.lla!rors. .Kli¥ie O'!lJi!dMe:lc U 2, B) aehieved a brea!k~:hrol]ghwh.e!:l U~c"yi:!Yvcf.ucd a nlod,c:[ for gmphel1e' with Spi~l~o:mi~il1iter~IiI:::l~O!l1, w~mich reveakdaJll i:rtS;l'~~3ling ilittute\:\i'it'lrul'OiJtIllSt h.e~~ca] edge.ode:~. ~.e",the Inodcswi~h o~p~site :spii]TIShave oppos:ilie dil:ectim'ilISofl'l!l"Opa.gat:L'llrl. When U:le·llU.m.ile:r o:ftliLese he::licml. ~iCIIge nlode'~ iseven, seme 'pe1iil:iLlnns;tioll ]n~nces. the hy~ Ibri.dtlEtl:OIIi ofthecse helical: lillOd.esB!nd. hinders n~.e]l· pmp!l:g<ltion'Ulis does not OC01],vto!v <IIIl odd :llIunlbe:r afmo~es, where tJrnte p:oopa;;<uioJl ls ::.i:&Iijb.ieand pl1oteiCrod ( see the right ~:I:.fllid of nJ,engu~re}· .. T.he l<illttc,rn-ease (1(1rJie:r>pm.l.ds to. .11 11l~' class ofb,md ilml:!H.tI,~tm,i:.e.,.~llC qM~.lmm spllml li.al~.systelmll, ,l;D1,d]ithemmlf'rU} the 1JiSl..ki dudaooe..l'hc
(j()llGUctafl!lice: sho%tlds:i:lQW;EI m'll~d
!it@:fi!iI"!I!rlQ!!l

iilmlllNIli~.s

decrease ali 1'ille'nuq:;'nelicf~eld fj; lI1CIJCa:ses" wlm;iohKDlmligt1 al: ~dso ()~fuser\'eldlf:%pfirimeMi' t8ilJy .. ~n tbis case, tte authors dJi.dInot direct]y

measure iI:lirle ~ iai,],aonlCruct3:ooe!";wliIJ:chis,not s;pin ·'qI~mIlllii:rm:."Thisis~ause., unlib!, Ihe ch~e, the t:O'tOli] sp~n is not.lI CO'r1Sietvedqua!ru ityi n the wre~el.lce, of the sp~Il~:rbit ~lltet["u:;tim.1. Thererore, altoolillWul the ~dm, fOtt1m.e~iltiJl~C

~inH.aU ,eRect

d<miiif:L'I;;1J~:OJ,l,

oftlii.e:e.!ectron

m the ]l1sullloo;r

simltes, in :oolids,.

I~:& to·a !leW

m~

Tile impa.ct o:f'trll.s;'\\\!'Oik\<\1;11. be f'ar..[t::a!cliii:., i[!gbeCl"!il.l~ ~t~~sofC,~c~~dlhit!there ii.:..~ruF!.·' d~u'm.t:;lmlt~~lyiflcf>0l1t ki!ldS: of i~lSt:dll!~'Org.E\H':~l d
adler 30 ye~I:S,·the biSJnd~~eol)'orlililat:c:ri~~g, st.ill ha:!; n~! 3JlltimVIP1.is[ing.as:pe:clS. A mm'e ,collillplete e]:1'!f!lSJi:fiea1itC)ll scheme: f'Or thc,se:
unusual insr~~.a~i]TI,g st"S!~es i.sn:O"IvbehllJ1; 'CO!fI-

·~.cstill remain ~obe 8lMd~d s

implk:~.tio.l1I!'l,ifb~th~ l,11agliUe~;o.:h:mlJ!5pwt proper-

1.5, ..11.\llmU~/m •., :S'~1li!"f'0l94, l!.~B~ (2001). 2'. 1.11 •. ~m,I91!?,tm.,.!i:ru""flG'i!' US, ;.66{20M~; l~clhlu~1 (IlIL'm~·.~O 'S~plBf1Mr.20arr (;IO,!l126lsclllIl!lU:L.a:8M7J. ~" M..~"[I')'G}:liln1Jl1, v. ~. r'er~'. J.f1iP l!til'l.l.3 ,,'M7 (197D. 4. :5,.I'!~~~abllll~~. INall'l"$;!i" '5.-(. :~I"I'!g, .Sdence :3(11i. IH~(,003,t 5. J.5d!!lgil'~e'a1 •• MJl$. ~ ..:~e,~!;9~ '~;;!6!!l0l (;21004}. 6_ 111'_ ti•. ~d~D, R. L~")i'!!~~.II ..( Gti.!:urll. 0 ...[[I. lmi!l!lballt:IID,. Sdmce .10 is. 1L910t20!J):l). i ..}. l.illill@F~fl~.II!. ~".!iI!!M)fIo!!'. SIJir:JiIlI..1. ]i.JI1~w1r~I,.~~ W [, ~\:!L-: iIlU'. '9'4, 04·720.¢ (2iO~,}. a..S\. 0 ..VdLtl1!ru)~I.~"1.lI.. iin,kl~arn. Nlfime.44a 1;~ tl!:OO6t 9. E.. 5ilii~l,M. llIliilllal H.l~[)',aji"1I.lI, 'G.Tatara,~pII .. f'Jw!i. t~N,a8, 18ZSQS'(Ol:006l. :W. T. !<hriiJ'Oi~· ~1.I"P.~ J\t~lI!~E'Il. '~!!I,~'l9'~1 Cil)()il'J', :li1..5,..MIJrratllill~ N,.lIta~!I~~,5,.C llllill'l9 a 'Phys. :f1,1rn •. ~eU_
~3,. iS600~ ~2M4)i.

s1t~lllclm:l.inc.lm;l:iing the three-d.une:liIsi.onal sys'~~!5. ( .1j). ]=:ventmUy, the fJU<'lI11fillinspin Hall system migl'ail ellab~e:he d.es.i.~lof:sp:rn eurrenl t 'cnF~mhsw:if:l],(llIt di sstp~timl.,wThlii.ch w[U open
lip
11ie:'i!l!"

:l!2. Col KJIII!" Eo ~lll.l;~!~,tRllj£ kw, .~i!'I!t..9!!i,li4~fI)2 '(20M). 'l!3. e.t, KIiI!I~,E:. ~I. e~~, Jill. 11:{!!I'"~t1If. !l, ~'68fJ):iL U M 9 '(2000) •. • ~. 6. A.16ii:m~~\ T. iL. H~~~,5.-(. Zil<lng.S"Q~~ 3 M. :!J5~ UOI)6). l!5. L I'll',. 'c. L Ka,i1i!, f'lI~. Rev. J±t 16". 1)!l,53;Ol{ZIllDn, :].6. 'lad:[ji~~I~ ~mlli!hl.!;Upplltll: liiliIill til!.! Gf<lfi1 ·1n--,Il,lih IIM'·~r grant IWimb~r~ 15 ro~'('06, li61:1i1'62:01l,and .H~OMOl.illKIll4a!;it:I~L Rt$'llaWi Grid II(rIil~iltj,'I'4l M~n(f«ij,el~,e' P.r'ilj!ltL Jr·1)11I le Mil'li,1ly ilil ~atjg.n. U 'C:uL\IS!"e:. :5pDrL~. !itie~eo, .andi fE;i;hlf!Dl,~,~ilp.;iI1'.
1

~Joss~lJilitilesin

Sp]I.lOOIlLCS ...

ASTRONIOMY

i~s-~ku,()f ~ih,e<Jllianilu:~~.~~!l~:~laU ~d 8yste:IWh It: t~rned Oll,lt fhaltrl:»e ph~e ~r,allsitkm aJOOC)lniPfIJ· ~s

iJililH:n.hnor02, ,13).. Soon o1l!fterlhe:iiCJre~,~t:i,Bem~i.ge't,ai"(.! 4J ,ropo8ed a. dlfc!fe:nt \~y ttl cr,~te aJ qiltmtwTI ~pifi Hal] syMM!L T~ley .IM~~d at &e p;liObICITi. IG'(HMmy [C.Bl!IWe~ as a pha~ I;rn:~i~i~ oofi,:v·~~~~h~ Q()~l'\;-~f!tk~Iil;a!~ d~e
A fi@W ~j.e-I1~rotiiOI1 oHE!~~S({lPe-s is.It~lpil1gll~,eo$~ar'd~~J'!l (u.!~id'!l! (Ill! f Ga lal<V.
@'iClI:!iIOf@trflI!1Sj'lmt

Me-rg.~th: processes

1I1Ikrl 'by. :!1J"'lOOmdt.:ross.~g,;',..,IhkJ'I ChJI~~

S:ky ami the: lilllllited ~Illfll.ingtime that led to this diSiOOV'e~r'y,ita:Wpe.:'lII:!lthal1'urr~ooreds ofsi:1llr n:~arevel.~;~;soc::cU:l"thmugholl.n't11.e:s1cy every dary. The bLln.·s:t hemids: a ~ew em oftrml:Kue:l1it discoveryofa singlernruo Ihurst so iini~eIliseth<I! :~t\ covery 3~ r<i.d:io3nd other\'N'<!Iveftem;gtils, driven overloClded U1.e detector of the:PaiikcsRadio by new tel'escotpe-s iljj1Jd1 ".clIY3Ji1cedtc::dIlito~oID' ]illlod.es ...'fheymbl1mliireiCill qU<IllltlLWl\.vc~,I, tmc~ s Telbsro~;.ei]iil Allslr.aiI,la. tor peIfO:rnlIi.ng,aJ;ulli Illrn lI[y.dng enormous SlU'" l;)!U"CS and chan!;l.ed the thickness ,[ of the '~I.~lIe The 311tOO\fS argue ttlltllt tlIDe burst ni~inatJed. V'eyll oft.hc' sty. outside: of the: Galaxy, pOfssi.bly Hit ~. dillst1l~l.o~ ~.I].h~ p1ii~ cenuuy, ilsliVOno:melrS ,esc<1Iped t layor. As di IJ1Clieases. dIe energy Wl:P decmlses ~t!de:voo,tJ.mlly clo[lilPSCS at a ,criiti.caldl]ckrlC81S of more thilfil 1 billion ]]giillt ye~['~.This indio the ~~fiJ.litedfqpcctrum,1i.sjb~e'to the hllnlmlrl eye C<ltes i1iinenomWllSalmdllil'l:p:reoodented [mn •• !'lDild evdoiped ~n~immefiitSilpilJ!!e of obse:rvd C of d~""6.3100. This gap dosing comSJil<onds to 'to the 'qll1:lntLllll. phase trarlt'i~ri0:l11 b~'1:1i"'C~1l the ]1L(ls:itym:;\<v-eIJ <'15 pOSis]bly pr1Ov:icl.ing fI. !:lC\V hl_g ,vavel,c~th~ foom radro '!Ml.v-es, .g;amnla! l!!.8ua]i~l]w:wr at d< de and ,quiatltJU:m ~pmllla'l~ g"1lm:od~r sllwyin~ thei:m~!yaI.ilcHc mOOliunl r~8. As ,IIlC suit, ref;(".<'!!n;:lliiI;e~si h<1'~ M1"Id<l gt:ne :!lit d :> ((~ K.511iget (rl. (lonfmne:d ~i.s by (10M)'., ,om!ofl1u~most poorly ch3r.aC:ll::ri;:oOO f!!.!_emu~ d~sco'Vewue:s tncludirllglhe 1m1le!lOIf!JiH;;rulliu'ing(h~: ~),.'Pec~ ~l~O'!lI'Iti.~d ioll.\1!tge 0(111C0l1stUl~l'll1t8 ohh(:;l]n~c.More detectiiolms "'""iilVC b<il.e~!grol!int~pu.l~il1!N. li!Il<'!sS]Ve Ibl,~ck d!ltel;a!~lQe O!1~istcntlJ wjtThJ ,!Ii ~~e~i~!,'!l~dc fQ.i" o could! give thcI1!:s;t CGl!ilpt~re ,eel'l!::l:~s,of' hoh:i8'1' \!m!g~m.!!i-f.~ btir~t~l. AUho1!lL,gh < the c:ach Qft!lll!;:.t\VQ ooge.s. """hiie ob~rvingamuch bflryo~s (Le-,pmici.es ~!,I¢h aspmt():!1~ :fIJlld ::;:1~9!~,ic~ky h~~ flO:~ bee~l:ltHy explored. t~l~ !S~nilJk:r ~Olldij,:c~;:!fI!ceat smaller t1~.idl;!lC8S, ~~,ec~ tha1tVll:)}' i()1iic:rtifin(;!fep~s:(itrt the n(."'!i¥ lena ]!III.CQpit~of' a.~~tmm(l!m¥.l'he ;;1!vailtiib'l~ im,dfu~t'in.gthe 1J$i;.W~il'!is:lllftitill\g sia:I!C. 'Tl1e "'l~ho:r il$ln th't l~ep-ar!l!ltefU. d J!i.$~~OIlOfillly:, U:rri'lNf$fW 'I'h'frs CiOll(l~u:$iofl :is further :bl':i:llJbr.(:.~d by t1~c CI~r.alljr·~TI'i i;(1. ,60]l ;LillI!! pbl!lll H.aU,1l,~,rkl!Il!y,0'1 9~ 1.20, "a:f8!me;~erspace h. Wi)t imnskllu C'l"l;:I.m; an;: UM .. E....,~il: gtmI'o1~r(Q)i!ll'llro..b@rk~L'i!}!.@du observed m a,]I\.Vilvden;gths.rn,a. ,...:ude \:'miety :m.!IgrI1tl"!:icfi:elddependenoe orOle dllftil'gC OOila

rIlninber of ~lenM~ edge modas, F'I!!tr~lrL(::rrfl1'1):ro,. tiLeyp:m~secl a sped:fic g.ystel1'l. Le..IDequan. ~Il'!! \iiJd! 'of CdTe!llg'fe!CdT~. where ~ilid$ phase tl:!m."imOJloou1d be i.I:v.:il!,lCcd by cil!!lngi.1I1il ~,b,eldcknes£ohhe .UgTe ~aj'ie[·. n~:i51was :<1 t :stmcrmg [IJImposail. <liOO.:!Ippe.:l~~;lg enOM.gh~o mot:il" WI!t!:! cxperu:nentali.sts to tryre;sli:Img h. Kiilllg eJ al; nawrepeet tlit~ e,,"periJ:l1le~,lttl.~ observarion oftl,les.el'ohust hd,i,cai, ,eaJ.!.!;,e

tu.m;;~.e'lliitsources ~lrn:~t: [ptlJll;;e.tilickier. :burst,. !!!OO bln·p.~ 'l.liruc esteee e~t maJll]fest::ltu (llJ], of l~. m sueh .elPli1temer<l~. p~en()lmJI!eni1l •. LOI:imer etal. (l) re!pcnt 01.11[l9ge Tn ·of'th]s issue the d~s·

bscr'\I'Cd at radlo \w:v,eI~llg~hs, the sky ~~. revesledin :~ce:~.t~e~rs that it ss p.1:a,:shOJ$t to azoe of vaTl$ble ~Ild

ncutl1(llls}illil the IGM, ~NhiC:his Ibd]C'ved llO ;'loco:l!llltfol' 90% o.hhe ~Q'I~II~ baryens ill the ulli'l.fe~e. IOn the ba:!!u1': ~f the ~~liJ;al~] !i~~\I'erof

slkie:s<. Tin!'!SQ.!.II,~re KUomelre.Afi!'olyuitl bl!g:i!ll (Ip~~a[~iof!lsi!i!! 202:0.Thc fad~~ywm ha';l~,n~~: a.r,rays, @f (:iilp~l(? ·~mti!'!i!!i!:as; !>te.era b1~,d1i5h~sl\:ir mecffiwlm· a![Id4ilig~lir~ql:lem:)I' ban ds, . .
SII!:!1!!.!1!lil!i!!j1the:

~'Qr

~n~ 1000.,;I'J~IiJ~!li(;¥ iOOl!!Ild:si.'!!'ld

of cos;.i,c

ell1lIYlnJI,lJiil1:en1:S

fto:m s,mr~foruJf[ing:

space

1:oillii.l:;~ude ext~.'3:gaJhu:;ti.c

tll~,el6W>fl S
'\1l"!IS

new

le]fl'S(!OP~

(the' Exp oJ.TlIJdedl Ve:ryLmrg,e

['t)bryOJms,~o di:s'~I1[ g~~xie5" <Iumd oCl1llt~nleSC<l~,~S as s'lmlart as nmloscoonds. Tlinus far. :sy:ste:rruJ,tic searches lrn!W'ile only probed narrew slices of til~is mlD;]tud]~.uellsi,omlLl,t~:llll1ll:sue:llIt~:mr~u:llelelr spillce,. Th~i:\:is cSi,peciilrn]yt,rue <It radic wave-

IC()Jll,lPHl[Ido'JIIi'~ E:lI.peMSivCiill]di l[y

there.

ArJr3.y) wru~.l mm.oil'de~?otkmillil'iilitmle ~m:I.·e<iJs>ein

survey speed over 11brood wii,ve~eJ.~gth irnn!il,c. Adldrutiolltll prt1jec:l:s wit~rn, ]~nprolYed :survey capib]]il:y are lMui.erw<liY in the SQt]If~,l'I,!I!'e-r~1ern
1!JlIIi~cd St<llc-8,ithc' Ne1I:u;:if~llds.Ausltldi,i1,rn!ld :S:()~thAfricll. ASIJiO'\1I.'Cirful ,1lStl~y <l:ro. th~::;e

rengthsb~ca']iAse On~]esmall number of!.iU'ge

and (he h jgh eo:i!t ef t:e1,c8eo'pe

fi!ccililiefi Yvill 'bc d)wilIrltd by the:!ilk'Juaoo KilJO'ltietife Awtii;Y {:see the: f~g,ureh ~l!J:6 nexttlM~!e!:'!~ll~d I:h~ricful~Sfl !Df ~x;istmgarchivcs. g~!1r;;r<!ti(l~r~d~~ teleseepe w~th lOO times Tbis llC;wlIy d:i8COl!of(,;rod ~t-ra.gfl:!~cti(:: burst: ·from!l~.jort"a_!CmtDes, sl.n::h ~ ·~h.c·P,r~~kc5,tc'~c-- the ~~.!l8hiiv:~!y~d .:I, bfJ{)~flITay 'of PO\7i.('Crf~l. ijlll!.Is:h'ate~, SOIll(': (lIftheeh1ll1(.'iJlg.CS alldop,Ol:tu,. si,gll:S!~'''pro(lessillg '~pab~!!It;~es;{8). s~op(::a:oolhc Vr;:Ji'f .large Arr~~ nitie~for tra:!mlstent seienee, 'f!n,e fbcl~r5:trcS\l!l1!Whc:l'1! alr.a!m;;~eilu ~s um;::Q\~redinthe TJirueldt~iIiIl;a!tcIPri~c Hulit these teksc():pe~ bles a pi1lc:liilomCl:I:on k1m:()\VTllIS mt~ting mdfll) m:c'JlilJives ,udclltu!1ci'[lIoll of 1i1\Le pmgeniro:r aliii,d! ~(lhnol,()g~es offeris h the diseovery
t~lle~e(jp6!)
OO:iiOlDl'eGsnecessiity tD ooiidli.lict,exte~lsive tran~i~fI:tSl!i!'itcys (2'),

fOlie excluded in ,o:n:lerru opti:m~e t],]le :se'lIIrcb fur gal,<Ictic objects. 1:11teceJilil: }"f'.tllfS" asnonemers ~;lIiVeifOlJllld udler elassesof rudio trrul.sient events du:tlu~h <'In."'I~)'\S~ ofatch~villi d!1liUl, (4') ~s;'w,eUas~1:rol~gl1 ~ ... -: ---.:si 01;; :i""nlt~1 t~, ''''''!i:'ic"il''';;''[,_ d·' ~,~ ... ...,. "'J {,"" 'I-d- _... __ct _0 .... __!'l_ ... . '·.·:"""i"'\/""nt ,",~. ... .~~~ 1'lwse [.e:::.-ultgpmil!lt tOd16 lflc:hriCS8 ,of:suc:h phe-

of RRAT~ .Sil);:!,) :llCqllillCdsimngUm"~.I1 'pernbytes Qfd~ua :1i"(JI: a Jrn,f1m:ID~iLdol~ lnslve ~llhcs: .. Bath e diS0~'e[ies, wel'e: ul:mde Ims:(>ilbl!e~ the a.&:lUri.on . af!llnu.ltibe:Euu receiver tome, J1a:rkiestel'esm~J(l dmt improved :survey speed by an rn:de:r of ~~liiIgnJitude. by access [0 h~:g]D,~speedoo~ and: ~){ulliu:g. Ilme. :spQJ<ldic RIUI.:rbu:rsts <mebyp9i:i .. esized'i:o origiM~efrotn lWl\U:!ruiil~:puil5m; (fO'lnt~
~ nClIllI1:JJm,

trn:n.~ilentl> (RRATs)1 (J)-

n~.cdiscovery

'ObjCict 0:1"ho,st: clIIn. be ]~niPOS:s ~ble.Typic$Uy~

!cOllil!)e~lll:Jar~n~gus

dats! ~u m!,l~lC]p](: wave-

!i,mrs: mattplloo11Qlceperiorncenlis-

h~ngnlis~re: essential For determining the mui.erl:ying piruysical pmpe~,.tie:s of the: lnillit" sient. aswas the ease fOT galllllmB.~Tay Il:mrslt: ;!IfterglO\i\ls (,6),. Fnrtl1te,". a. rndi!ote~c:selOI)e's Ica.pm::ityto srwve.y bllrg~ <llrea:!>of the ~ly I.S most eill!~Iy coup.led toiowEl:lmib·u]a:rfies;o~tim.l; that is.lm:l:;~r.e]d:s Qf view <lire traded off-roT poor loca~ization OhOll:Ules.l:lill the C,L'>C' oftlmi:s

of $IT'opJ.iilrysic!ll I)~.leoo~rn;en$..Pul:S3rS:l :Sl.ljper~ 11QW.eSilld g~~n~ .. ill)l b:~rrsts;~U represers r elasaes of n.am::le!IWts01l[roes til a,t halVe been funIJ!1011<1l1"iIll)1D~S ofal bread 'iil8llie1y o:f~}i<)1siCEim pmoess:es"inc]uding: cos;ooo]0m'. g<IJ~BXY eW~iUttiilln.the basic properties of dense stair' lll<Iiltc:'a:, mild.genel1dre~."liv~ty. TJle bmst tmmd hy .Lorim:l" et (11. is aremindee tiillrl~:stilrtli~1 diseoseries ;iIII)(l :stmto ~e MrnJle..
lR~f!!~II«!!i

suon} [oOl:wd in ~l'ue:Milky\'tHy. ]3oth ltiRAT~iIInd the ~tr'lIg~bu;lilc b1i[rst were druscov(!nd.thrOl],gh <I .c'i1iIHdysi.s ofdata 0I'lJt1'li:ned for 3:~argc~~c,iII~epn]s,!iltsll!tv~y.

burst. the bunMi'sloc;]Jized~o

<I r-eg,imml(me-

Giv~t'lth(l s:i.fI'li:larities in iIIh()wpro;pcrth:'8. rl1c

~n·ag~iaeric' burst eOl1l~d ~!l!¥ebceml :Ibu~~d ~ tih~ datil m[nllflgtha:t d~eovemlltR:.AT8. i!i1:1tial seerehes f'Of bursts, hO\Vi;Vert\VCr,e opnstraJin~d to c!\)vcr ~lil!I.y ~.~arr'Q\l;Ir~!~gco!F
a pa:li!:!JW!e~~:1 k:lJ!;O\l;t~ :~s d~:;;p,en;ilof!mi;~~~u:re.

n~(J

'CJlwrllerthe size ef'the MooiEill,.rrmJd['lg Uru.(!IlllC: ~deJ:IIIlif'i,catim,l, ve!rymrl!ikel:y~ In the c(m~.ing: e<a!fS, Jrewmcli.o w[~(jOj)es, y \lll~]]diramati1call}' c:l'ttcliWdi ,oW' c~pl\libUfuie~fur tr~m;;!c~~ sea:re:hcs. AU .sJrc i:!1t(;:rrtero.~tric 'I "'I'''' ·~,I 'I f-~ I~JI ,iiliI1'fi)'SUiit ~!mU tfl!1(;lou.s',llJrov.!u,eWKIt.; .. :l~.uS iof,.i(:\'"v~i'ldili(iCttmtc $oonx; ]o~li~ti()~l. The An'ell T~]e~()~peArro.y~w~lich mcc:nUy bejffial1 (Ip;r~i!:ion. ~~I«;~ use ofn la~a~y of sooU

:1. I). it l.!lt1f1i:e:r. j~. iili!il~f!J.j1~. rMLa~gI1~ill.O -. 1- Niafil:1l~k. It. 1=,. (~1lwrotd, .'f:d!!~Uln·' !2JOOl);p(jlil1~oo aHl~~ Z1 5!!pMm~r :2~Qai(1().112,6~~-rI@~~,1147!l3:2~I.

whid~

ch~r;)lC'tcra,lJ:=sthe

'efliec:ttha:~ inter-

dIshe:;lbr unpn;:oedellt~d survey c.1p~b~~ide5

,at omlJllune1JC,i \';':a'\fC'h~ngths; {7J, An I.IIPIbI:a.de h:), the Vrt.'r'f .la:ug:e .An.·uy n1IU1k:es,this ~n dfectlli'lldy

2, ]lllll, umfe-~v: J. W. ~.aiiO.1 iIlI..hkl1a~hli", MlifAflro.!J, ReI':. 48. 14S,9' ~2004l1, 3, M.M~!.il'L!'DIhLiI! ~la':"I\!Q'IW\Ile4::l:9,·a·11 (~I!l6) .. II. G. C!lowe~eI.l!ji.,A::'1i'~~,l. 666,3:46, W)07l'. S. S. EiI~Jija'fI eJ I!lj~ N4ltt.r~ <134, !i'D,(2005)6, il. ~i'1 :P~r~clIli~. i!ltlllM!!liIMtflu.ii..j,~ til [, W.ijI!F~ MIMI,. L J ~i'.Affl'i'iJtJll!i.lmp~, 3::8, ~.79 (2DOO). 7. 0. 0It81l@Ietllj"f'mr •.V'/£541l:!!, 102~1(21004). 8.. C. CAlMnl. S;, ~<lwlill9l!;, lVewAll/I'M.lI'f'IJ. 46. 91'9

slen@jI'a:ndi:liii~ergal.f1cti'c plasmabas all a pn~pil!gati:~g I:mJduowve.,. Extend:ung the search l

tlO~O..

Thl8 P"iwi-p,iRNA P,atlhw8lY Provides B!D Ad81plive D'le,f:,e'nse in theTransposen Arms 'R,8IC'8'
~~~I~~as'il",g~y I':~!i!i'lpl~ fI~tr!\!(ld:!!) of s!il'l~U1 ,RNAs ,~u: 'thI!iQlllglhRNA·ijl'l~fIlr,~n:c!!l Ul:NA,j~ PQithw,aiV·~ t(lr,~glglme g;efle 'eX~Sislt(!n~ t(!I m~~l!Mf! gl!ilt1iviilri1!l,f'~$PO!i!~Ets:, c!,g;.aJn,~e ,~hr'C"HIS~mal~ ':tto (h:HliI!i'!~IFISi.il!nd fe'Stiralif!i!,!! sp:re,ad of s~lfi~n 'g,Ei'n@tic: @IEliI!Ii@!ilts. Him:lfi~aUy:. RINAi 1i!1!IS: OO~iI! to, dffi1il1 e,d asa re,~pl!lilil:5le t'O dOl!l'IIll.l!'·S'ImimdEldi IRNA. HO!l\l~~!;v,er,salmI! :5rnal~ RNA Sp.tlIC~:es, m'il!y 1111 otari~e 'ffimml dOl!J:il,le-litll"amded IIUi,I'A premr:ljl[lr~li. Yet.. li~e mi,~rroR>N,~ ami! sm.all llntellfi"'eril'lg RiN,A~,~l!Jlch ~plE!C:ies; uide .I!Jrg,ol'lal.ll:tI:! Ipmil:-e'ifls,1D 5iHem~:lilgl 'ttl ~get:!i;tiuo l!I~h C!ompl~menra'l)! bElse'"i~iilm~iiililgl. g Silelil of'llg (g:iill b~ ,ach~~ltedby 'bQ~~(nd:tweelnt ,@f01lt:C€SS(lry fii,rulr'5 or th,rl)II!l'gh ~h~ ac:1iVil,ty o,~

fW!lcliml of :Piw~ p:roi.ei!l~wt!5; ~nQ~U!!m discovei}' (If Inh.cir smalllRN A ~flJI1Rm;.

'iWi":llnill!li'iI,cilflgRNAs

U1ioC

l'h¢fi:fflti.l~dkaltiol~ ,of.a dL~ti.I~(:tpopi:i.!atiom ofPi\:vi'-~SQcial~d $r:Jl;l~~ RNA.SC1l!fli¢ .fiI(I:!tl studies in !JJ"O!..WJJ-J:'~ilQ,. The p~!~l;le of 25- ~o 27-!i:l!ldwlidlc {!11)~NAs :hamoliogous l~ die
rc,w,e~:i~ive Slell(1.re loc'l.ls wa.<; (lo~c:Ia1i.}clI 'w:~mt~ i~s Sli.luRcingaUlclii il'Cl~,I.IinOO tlt~ :P~w:i c~aoo:promciili, Aub~lti'i (t5} .Pinfllh:tg(:!f:so1l1all NA.q IfiI~ro~l~. R

DJ't)f>r')pl~ikJd¢wn.Q!ll1il~I)jUpla~d St~NmMp~iffi:¢ 5!~ RNA~i!~IJ;:iI,a.~rel~. dt'fi'!;'~ oon'!'!iW'" 'i.ous:.lith"e elements, C<!Jle($ repe,H-.(lSsooi!Jled s!llOlll~~nerrerl~,g R"'1As {msi.RNAs) (J8')'. A diroCi~i"ICra(ltiA:i!'In. ootWOOJ1l a:asiRN 1\.<; 3~1.dfii,,,vi p:ron:it:tS "WaS de!llliOf~tmool by ~m.nll!l".op'rec:lpl1:31ku~ ofAw~. tIOJllptcxGS (5-7~ JOj, S~MII RNi\s 1liS¢g'l1!~~ltii,l:lJJ'();~v!}lI:it(1 'm~RNA.. l~~oo~t!

ArI!JO"'aJU~ iitsilllf. whkh (lftlllll has eJilId1r)f!1l!ldr('ld~(: at:tivIT~, .. Asa ~pll:dfljc ,!'!~dad ~~till'E! reg!,!llla1o~ ~iIi~m, RNAi i~USi~~ ~n fot!ghout 1ili!!k.airva',li\ihiio1l! l!illdlh:arll!s iii 'long '~oi~uti(l!l!la~y hilSiOOry.A ll'ikeiy ,mlJ 1II(1iOIiI 'of Rf1ijAi tlilrmll'Qh:oultitlhfrt hri.s:l:ory·~.ropr'Gtect th@Q@;IiI!JliFU!fra:1iJn ootlil p,arthogl!lIik .an~
1

id~tiiRedif:l!~

.mdovames

of:;rebrn(iSh,. whicl~

l~aJiI:5;'itk im''Ildid1sfs.

ill COlillp!i:lX. wiit[h. ,(fLs.. t~!~Cl~d1k~ .gf !'i,n11!!l RN~. ~f!nlhe core ,r)mllll RNA~d:uccd ~~~lCl~g OO!ll~ ~~ex (RI:S(;,). I~h:RN.~i!Dtcrfe!le.llce (ItNAi) ef~ fcel:ru'oc!l:n;p~cx {I), l'1lm Argofn.m.ltc ~pi\tfm1il~ly !lC,~gatc;:!> iHIO 'l\OO cikldcs;, tire: Agp cliadc and: 1~!Ilfl.fliwi. CJl,a:t:iG (lahh~' $1], Til('l surn,gr"" .lio;sl.cm :y'~iU ArgOOiU.ll(:: al1ldaUplaut ramHy nu~nlb~ Ibel{lI1i8, 00, 11!1!~Ago clade. 'I.\I11~" ,cili<ll!~ ,~ldi sK.lJle!:l.JOld.,,>oontlli..1l !'!rom1ileD'8of the Pi""" cibdC, To.getlleu:~ I~ihese llucii!'ligs indiC<ll:e '91,U Plwls:OlIIlcl AgOiS ,a-i'e siJil1i~ar~yru:Wioot An:[rllal.gellm~ typ'" tcany cootain IJ1I,mlbcrs,ofooth d8d11!;~a11ldl ~.t is Mcm!llin,gclt:ar 'Oilll this div~~IDn of AI:'g{m't!.u:r~ re!Wcl~ I~heir!.lrrldcr~.yi!~sO:loioS,¥. Ago dll& ~)fl}tci~'lS loon~p1ci'l.w:i&. ~~ioo,RN As (~liRNA:s) and. 5!ll1iU imc.!Ifering RNA:!; !(si~NAs]\ wh~iI.derive Jroll.l oo1JlN~c!fw [~ (dsRN.A) ~'roGt1:li'SO:C; 0). IIlli]'tNA.4'lgo OOJil:'iplif.'x!.':Sro&Jec
rgmtw:ilh':pm~irns.,. l~iIiI~lffinslaJliQ:illa~dI ~ffl:bmty():f fJm~£iJtl-c!ild'tlilg

de'jn'O!1!SI~<ltell e!,'(lll!l~tml@lY ,ool~!'V<!LiQn of !!hi!> snul!U RNAeiass (/9). 3rtlaU RNApar1ners of Puw~. proDeul1l.S weroallsoiid.maUied ~.Il~n8immai" Iian ~q~es and ~cm.ed. !PL,,,,~..j.nlm.Cltilflg RNAs

~nlNAS'. ,,,1'£I)chioolil!llt8:in ,111 i!.I~rEilpry ~ 11I(:i~ii\{(u'k ~lhaJ;in~iP<lC!" -.,3~ {lIh!l ~l~ . slRNAs 'i!~ IJnr ,Wpll.if,'l arise rro~l 1~~gJJ~hJlilRNAvil!'!U-'ieS laud! are 'cnu;ie!i~ :LUaH~'~va.m1 hlln~~Il'C~ IMSPml'Ses {ZJ_
I:n CaeJlorir,aiMlitt.s elegans, CI!dcigCllKDllS siiRNAs (iI\'er1@ipprolcilrrl.-cOO~lilggcncs, .md. likely partieilii!flne 11il.g~~G oogu.lalio:n, (3).. As das~,fiI.egthcr '\I'i[lj~ilri'!)\~d 'nOO'" endpg~1tlous film.NA'l haV¢ yet Ib~r! de~ribedi hi Ye:!1~bn~es.

The! ,Pi,wli 'Qgld:~ TIlle Piwi clade is f:m:ill.din

so (')f,. 3I.tdil$~n.,oo

mni.il1:l2lls; cx.ru:nillloo L~tigMycorrelf!li!cd wilh,

an

!~!Ile l,lIl1crgeI1C£ of sp~~ alizi1':d. g~m

cell(l. M~t

Wal:OOO School o~ B'iolOg~CD!I,s,ut:QCJe:5... !H~i'lr,d

lfIughes fj.1l!d~~l 1~5nMe. Cot'!1lS~ni!i!~"'arbQJ laDcfOiI:o!,)"l [l;UIi9~~ Road, Cofdl~p~ifil!!l Haltor, NY:Un4. USA, 'i'lhl'.I'i~~'l!iUlor~CQifil!lMI!IU~ equ~.~!tto the 'No·rk,
"~'ll'o' !'lhom (Qrr~.spood\l!'IlG! I!~ l1Ioon,@csh'I"@du sliiouldl be addressl'd •. E-mail:

(piRNAs} (21J).,.A:~n.h(fugh! 00i': RN.A:s ~ some r~~I~with ~iRNA~ tll~ am: a1~ !'lu'b~W1~ sian speci.!ic<lUy ro :germ ·c,e[~" lin.blw"Oml;~, an tiai difi'c.run.ccs,im;;ludiHg, :adearll~ of ,'Jeq!!!e~oes ITIlilklhi~g fi~ili vc elcmcllil)s, NOIile~le~iS;, 011 aJlJllmll1ladaclcse ~o IU~C blialerirnl ~~.Ph",is c i.tlCl basis of drew!'cooumma. 1~es,. we rufer ~CI EIre' expressed ill ~Jm cells a1JldllllooMasls. ~d~f· u farcl1'1:i~ !>,~lm;'IooHs~Insiiblc fm the ~~:nrui:~ S!"l'naiflRN I\..:!; in Piwi ool~lj)le)i)es as pmNA:!! wiitla. ml~rege.~el"ativ~ ,eapa_city {)if I!lh.esc orgal~L:slm; wiRl\1\s lOOiI~g ~dru:~ one su.bdass. Pi\l,ih~ !Iud pu!lll\lAs ft"J;oo a. ~ysroa'l1cill~~ilil(1 {f). Ahhftlili£J~ l1.ellbla.'lI1~ 1I11'i;: ooli~:id~~ S(lJ11Mic foom Iillle cau(u!it1!1 RNA:u!lnd aI:li RNA ~a'IJ~w,~,s;, stennrell:;;. 1I'1~ O'I!UiC capablie OfgMllg 1I:i'\'C Mgenn ccl1s. 11lus, dleOO!~rve:I el'!p~llilnpal{CIT! (If No a...~ia:ilion 1X:lwe.e!l! Ph~'is ood. !'l'~R_NAs\"'rm> detected i!leidler [Iy (5, 6) or ~,{)!Jlse(21. 22), Pi.wi proteins is il S1l!iO!lg i!ildiCiilim] of iUlcir. vHilI] I'iIlthou~tn, piRNAs, ~1.k() miRNAs, can:y BI 5' ~iul!.l!i()llin, tbe ~lJml Hme, TIlle gmm]~E.qof ~llJjtlkdtu1Iltirarl~ma:bl n- IlHmop11lOSphailC:gn:mp e 811d exi11bilfl pre:J~liCmIoo fn. a 5~ uridilw fL."l:tdl.m (2.1-23).. lin. OO~lraJ>I to coda I:nI!l~tilPlePiwi prul~ins., Bm Inhme .DfIi)."Opk!tI!iRNAs. ~y Qrwi~id! ar,e cO:L~~~rvooii~l!!gh ilaprole:l~i Ph",,~;,AlJ!,l'~l].ttle. 1!DldAG03 ~ eVoOlulio~.t~dJiYidl!!<!1pi ~As, ,e.x;~ed In the n~ale a ndfcm ..le gmn ~~es. !UiilWio!ls of}'WrS Piwi is addilimlai.~,yexp~e.d in lIre SO:~lill~ic e:tliepooily COJlS~OO C'lIi(;ln bctWOO_Dl cio.scly re:l.inoo. s,pooi,e5 {21-2J). IPiilitN'As.in. DrosopJtUa ootls, \V,lildh are in close conttlcl: wii!'h gcrnlHn.e (S, 6) and l'L'ulI:Ilsmlls {2.1-.2J),a:s\wI~, as :si~NA,. 00115 (5--,K),E.,'tpffi ..s.im~ of Iulna~~u:ue l1!1Ot~pro· , lUllm scan RNA$ dUll! b:Lndi PLwip:ruIteins it] ellIllins MIV!ll (fIWILi.), M]U (PIWfU"),ond. M1M2, (Pf'llVill-M) hi mni:nly f,l~lrn1011~d'1('1 rlile iil~es (24),. are stI'Ib~l3li1ltfu11y longer (24 to )0 mit) . ul!tle ge.nY!:lliju~ (9-.11), A~a~.Q!,!,g[~. ~~iQU ·of jJ,lOW!n~:~R.WA'j a..w. ~RNA~ (1~. kI 23, IrlO.· UUllik:e Milii,~~!'eJl<lI:a]ovaries: ha'3 'been, repol1lN, (9),. nQ mnl!U<Ji1,~~RNA~ but~imilill!' to pJOOtt !.n!RNAB" fU!lctiOl~ for '~wisun Il~e f:eJ~)~te gn,!!mma~tL<l.u l.l!RNAs al.ny ,ii, 2 'Obmeil:lY! mJdUlcar1i!on Jail: ~~cir 3.' ~m&, wbiQb is ad&d bYflFkI~~1 fatlli~,y .RNA genll Hm: ~~asyet b~l~ degUQl~slmted" Corui:S1enl with d:t.c~r: exp1l~si(m paltcm, nUltil'ly.l~fcrnsc (25)1 fi'lilflilly. ~n~Dio tmalyscs .PI':wi IIlll1Jrul1, ,anh,wa1s c;.:bibl1(!ll:fecl'll ing.ocm In,m,es (Ui) :u.K!. zCbmi1sl~(1'9)' 1lCgU(l 'lg.a.in:l'>~. a ml!G f\l!t .tHeel, a:k~ emym[': ~n miRNA ru:K!. ooll d:e"'~10iPllli':nl. D:M),'ir:1~/i,l:n Pi,wiis ruqll.iF>ild. ~RN'A biO@~~m~tnp1RNA ~rodtilctiQ.li!. b!IDle !r!l~il!i:e!!"Hl.ceOrS,~nli!1ie Sie!\1 ccli5'. b0dl i!'l·~~ ,md ov;w!cs O.~,~!~ nlQ]!Se, :all '~~Ne P~-w:i 1~: G~!1!Qrrrii( 1()1~!Jili! ~f pilRIN;A;s ]lfOleins are n,onR'!cln;l!ndantIYNqUl,il~CI ['('It ~I"" Ill!llng~l~'>i!l {10-12), Ald:rough OOI.W~ mm!li~ic Mos~. l'lMs'()pln"la piR'N!As mat<:h repctiinive elc. ie.x~ii(l!n of Phvis :lms boon,~cdl, nlUJlnut IlH::nlE ruld, d~eme:~ore: Illiiap I~O tilL':g,L':llrnne ]11. runim:::a,11'l ltck o.'b<",i()ul'l defLlCIs in d~G iSQlmcl, 011 dmz~l$ kI! IIii~QiI,WU\ds(lif 1000a!!klllf,l. V~t li'iI~p~ng O:le';: b&~~s()f their I{ls","'"olt.fumoti.(m p~,~:llotYP~i of IlihgSc';l firRNA~ th:Mi. o.'l!lkll ~ plac~. !:Illiq)lJ.l~'~Y C Piwi prolei!i!s: were ~~:l!.cedlin s:tgnaling l};otth- ig~ U~e,gC!:IQ!i1e: ,~e,g.j'[ptRNAs rIll!!'! dhre~e"t ~,~ ways uooeili~ying gwnlil~e devd!op:~nent Va. J'.f}, peal co;pie-s) [deillifOOlcli aiimlrod set of discrete HG\1i,It.'Veirj Selle~ic studie,s a:lso(Xlililltoo,to <l role 1.001~h<ltcould. gi''IIIerise tomoS'~ piRMA!;, nesc. £bt tI~Piwi ~a1:hwayin si.k:r.ci:ng sc~:fish ®eUlc~i(:') W~ du'bOO{l. piRNA ,ctMs,I:e~ (5), jpUtNAclllSf. rorllliililt1ge from K~!lI. lD :hllmclOOdl.,·of kjiltilhasilS 'L':l(l~itI~ (/5-J7)~ .h1l!>Lglt~ ii~to' d~.e iliICi!~Iru'
3iI.tinmals ,SL:jplmUegcrmHult): .3Jlld. sl!}jm~.ic
Ct:inS

~'l)'

in d~wcl~p'!!)i)~l,aJ!lI(jl~ctriwi

expre.~-

or

REVIEW
i~ t~giJ~, Thrzy ~ deY'Q!it;l. 9( p!\Otei!] ,oo41~I,g g~les ,nidi !4t'lt~gjilJle high~y ,e!lr!c'~ed in IWal15'"OOOJilS and O'tber~u; (5g. $,1). The vast m.iI!l~ jorily a,r ttaI\SJiIDsom OO1il.Wn.tin pilRNA dllJSl~ GOOU!~ lin. lite: foom .of IteSrocl~ IWlUle'9IOO,.or dam3800 .,~i~ 'that ruUil!; H~~ly eil~ab~~ oO\f'a'"lunml'tot (iI!t~t.I~ ,~'!';p~k~~. Qt. Itfiooiliz.llioo. Th.e,~~nOi.i: OIlft~'JjXIS!lMe ·eI1e:if!'ePil.!l:per se isnet s~flk:ie!ijt oorplRNAprodltOiioo. Vimmlly <ln, p~~Aclll_&
, IUI!',"ISsemh~:eid ce:nll'G!il'!e~ 'MIE!mcl!ir~111!'I 2, ~selll1blad ~~n'ImI'l1:el'ii'llh!!WrtlChn:llJl'iiIlilEm

th(l~ i!I~<l:~ !Jmr~~~ do ,!l!!"!!W~~OO <i!recl)~ve:rgedhn~ CQ!~!US~pg. lentiaiJly adive copies: (lig. Sl ,. ,P~!IllCh!Y'I:mle piRNAs are fOlmld jl~ gCliJill oo:Usbefore nIDLosi5 (26). Tlhl!(lSC ~Iare: the 1l1()I~cuilaroftlamotcristioll
~~>;;:.

"Ii!.d ~""

CQ1~iP!~);e,~>iiW!d d~

]S ~.~ O!!!.ly b~.]i~y r!fm~~lOOr

!rngjSjJOOO!1$

tI!>1.t is 1.~'!Ie!;!i,;"i!11,i n ~I!!,esmm!!~ic cells QWtll~

O'ii'ELIi)' (5).\loI1ll~re flali~'(~ru)() i:spl:'CdJ:nnj.Il.{\11JI'~y
~xp:i'c-SSl.'ld

of pilelii~~i!;it'l!l p~RNA~b'iid(i1D'ig!l~aoo fl'!OIIiI ill. dif~ f~~IM s~, 'ofcllL51_~~ lhat!i~Q:re ¢ld6~lyrnlaJlth Ui~...e g f Dro.~'OphiJ,(J and ~ebfd.~I~i" W'Cpea;~
OO!1:00!Tht

Ul;nd_i.ll;e.cmnls~ootingliRNAs ~Ilpl!anw., piRNAs i 00 iut .~$,'; lTD]] dii~rn: ina ~ct~y lphru;~ m:<'ll'iilerb~d~efg~,gim1are ffl)m ~~l(i~.ait po5il~aJlisroo,rti~g P!'OlfioUillced peak:!l: ~mdg'lps

of~iR.NA dCr'lStl'_y(fig •. ]). piRNA JX1IpuiIOlt~O!ii> are (:.-;xmron):ly (lQ1illp~e,''{, with ow' IfOOCl!lt esllmt!'l4lL1S placing the UllIi:n'b(:}jf (iif disliit:\C.tI~.wrumliliail. padlY.3, Ei!!!clYGmalJ'n

4 relMlerklttet19cOOhlii)~J1mI

Ulitep.iRNru:

all.

>::500,,000 .

Bi'Dgeillles;i~ 1M p'iRNAs
'n1i!l

_k (If a de;p'~lde!l(le (li!~ D~(lef 1(16., HI) 0lf:'idI Iheprofoond s:lr:l:ll1ld llS)'U'nneLf)' of uliIDIJIH<lli!'lrl.

iiiiii

~iR_NA, ooMrly l(pbJa &tmn~ ~iAiN_A.OO!Blty ,(IT!lnWis, ~aid)

"

-.&.

'

.. ...

.. . 'II. _~

..

... ...

IlffiJil~)IltCil}C clu~tet:'sindiMtc: 0]",\( piRNAs:~re noOl §cn:emtOO, room dsiRNA PE'CCttmlrn'S, I:n Dl1;mop1~ila, I~i!>~ piRNA ch.ls,tm:ll g.cnc~ sn.'I3~~ ..RNJ\s f[l)m bod~ !!tran(b~ 'hQW~vcr; IUner.e .~ cx.ce.!l'" ti:on._~ S'1;I~1 115l~e,tlQm.e",,£'{I leeus, wl~~re piRNJIo.s Il%'q'l IIlm'OSl 1e.N.<etl.!si,\'Cly to ORe ~,eoo!uf!l) .~'!'dI (lil'l, S.]) (5),. 10. ;rob:raMS.h, piRNAs can 11iI.~ ~C!
bod1 gll'lOmic SUiIlltds;.hawC''i,!(M. \lo'id~[Dl 3i'Y .!!j.V~I,

"'''

...

". ..- -._

,~... '. ,

II

,,1 ._

.. ~

.1 'iliiiiiiiiill

II
....... + ~

l'~PIl@l'l!)lll1

p!:i,le, ·slfl.;l!li!(;J
OIl! m_1IVS :S~C)!I

.._ ' .. - ... ~ . ._ ' ..

1I'ar!sposoo

" ,'

.. '"

'. ,

."
_ ....... _

rc,gi(1nJ of aeiUISW:r,. omly one .5lmnd gives, rise I~O piRNMfl9~ (h\liOO 11~I~e cO!'l8id~<!tioIJs., two p~~lI!Sible lTI:ocl:C~.s· e!~i.1:ge. The fi~t islhegieD!!~lh:m o:f piRNAs by samp~in!ll of long .sing~·5!r,allll:!edI p~lIJJ:':\iO.US, Allel1lmli.vcly;. I;)lRNAs 1J0'IJ1dI e made: r as prirl'aary lI'mlS.erip1:ion p:rodiMCICS" Eliklcllcn for 1i1,_conneris the lack of a 5' tnp~l.osp.\'a\atcgmtlp J and Illil~ (I~ef'l.i~liOti IliIl,'dtI single r,~l~I1'M;;"fiJ~~ll!ierlioo .:wI. ~lbe5' cltdof l:hefl,m./(l'JlC.o d!Jl~r pMVCI~"" Ij~e p!'1:lIdlucti'Oflof 1)i_RNA~ IUp l....I,60 1(0
away (5), This :Sl!!im~g~ySU:plpo!l~:S <I. nnoocl ill. wh~d~. a slrl.gk} Irma.s-cripl U:8vm,;!.1S a!lfl C1ltim piRN.A c~mU!:r and is sub~qIUmtflypr{!'O©isOO.

.....

..

1·

..

il~~o Iwa.rI1]''CpiRNAs. P.roe~~tlg of Slf!lOlJU RNA~ :ri'Q~l ~Q"gsluilg1.c:.. strn"-d'o(l tr.mscri~~Is, 15 not U!~p!iOOedcnle:i [ill' . " .. .... ..... .. ~ ~.... - ~ deedl, Il1l.RNAs ilre ~fOOesse~ fllOl]l prool,morn ... · ...- .... ... ~ r AGOe: ." .. ....... liliilit often span scveroi. :kikibases and I~hm can. eneodc :IDVeml ,Ludi.vidillffil IwiR.NA5 (27). P,i'OIlUtlJflood.pcalksin fJdRNA den8illy ,¥idlirn,aeillsttr also hill~.illh~ C(f(r~ten.c(; of specific:pR)CBSSi ingdietefJIIlh~@u~s. bowever, tile WI:attl!Je·of rnh.e.'ge .slgn~l!'iis ye~ ~o bereselved, Then;ntc[liu~I:'Y lila:!: [l1OOt.locs:piRN As :ftmn fig. I. f,(l;at~fl!:S (If pliRNA dlllst~~s, IO\l~rVim o:~Or(J$QPhj£(J mrom;Q!i(l!it'l(l; :2 iaiflld pfogr~s5hl~ly !i!il(l!'!l cll:lstur.a~ri,vOO '~sct:i,is mllm1i 'OcsOI:oow'lmt d~;iLt:NJ'llie:W of al miliDor IPiil:tlNA d:u:Ster •. l1(lldlbh~, <liS di:iferonl .Piwi pro4£1W in !:tiCs and m,rumrlnaJ ill oocb.illtootpOfljill3!), disl~nct.si2e Cla.:% of Sl!tb8i1:1 NA (5 U, R 22,) •. D:a'm ..lom. fl:{6-S ru:Jd. I~~ in .lJn~'(JfJ"l'l(Jam [00C31;edlupenoool.KlJ'I:'lenC G~nel<lny. cl"IlLS~!1rnin: nk~ and \'ertebl'"a~ '1';"'1,-'_Qln~:c ~k,"'''''''''h -;,.' ~!...... ,-",_·_fOI!·!~L _, ". '-1-' _I" ,...-'.,. -"'·'?"i~ W :]~_1 SlIgges~ (11_ ..... ght:ll rise .tg ~RNAs ~:<l!t <h~(I!i;i<l!~e wi:!'J! gl1~~t1i!le m"lPI'ln'!OOs ~1Jgg-e8t a, Jnoo~1 h] v.41lch [liRNA., p!'QPiwi p:~m, MQ~e paoojl!iene; piRNAs: join I~~i'!i~ Ch!lO!dm i~lm.ciu!:eI1~:Y p'tay a role in .~ d~ctio!l begl!!lswHI~s~~~g1.e ~ea¥:a£le of <I pri!lil~ pi ~A dlilster tmmsClipt ~:Q:genernlr; a piRNA 51' i1llil'lgp:[RNA. C~US~CIiS:Ptg.l). f 'oonl~, MIU and. MIWI: Qmlll~Ie."iies (:l7)" SilUiliillrfy. .DtVSOpilil(l ohlLlMlJm prodUce piRNAs, ~V:~licl~ ago end, piRNAs Ill!aY 'be. Sfi,nploo, Vii111fl1~yfrmu Pnm.loomt pLRhVil. kKl:l Me.fltiiO :foondin, !>{iI(liat!.:llv[lil. all dll'ii)ePhvi poomhl'ii (5}.Hc\lif.. al~y ~ion withJU a dtlismr '!,V'.ill~!:timanI)' p:reJ. nll3!inl'Wals (11-2'3. 26) m:tdzrnr.lifisb V9). Mam(l~OO ooJtllg 11. 5' urklltu~~ ~1JUf': .. AiTh(l:[l" & fn.oorpo:~ni3Jli,i11II. ~iR1NAs can be di_v:ided~~~to l\l;IO pop,ffi,!\~Ut :;;oum: cl!1-Sffifl> s~~t'(l piRNA~ ItltJai jcnill rnill)ll of tll(,i c't¢avedl RNA-inm, .r1Piwi. 11.~. ~laI~iO'.ll:S,P.fld.tyt!rn~ pi.RNA'i: ap~;ru:' aR;ll:!]ldi t!.Wl ~fi¢ . P~i IPlf(l.tcit.L~,lilroily~~ dlOO~ c~· f,(i£hyle!'!e ~g~ or!~,edru;[s, ~eo~.'!e eltceptio!'!.~ I~~ and Ui.ot1l P~w:t lPi~!\s \vijJJijv~k:l~ t~le~r aCltivv!y gCf:imIles lllile 3' ,~d ·of ~m~ piRNA wlilh t!~e specitik: s1~e detcnmne-di by U~.c;foo'!pclul of ajly a!bl:mcliant,iindi persislllln~l Ul:- :Impiokl roUl1d proaw:;tsassodate: ,d!tsplay .~clfic renl£KKl'l~' nd .. special ,e;x;pre.._o;s:[Qnp.1ltcnlS, for e~runple, /)ro., . sp~iilna1icilst1l@.c,,~ftlNwhi~h they grndu,,'i[!y <iliS'" t!~e Jlmicu~,1lI" fa:luTlYlllelli1lber 01] dlIeilNA. wpll;l-a piRN!l.s origiiiialli.ilig fro~'I'Q,he jiamilllbj t .Phvi o"irild Alllb<~~ii~c: OOiUp~CXCS Qoltltruilffl 3:p'PI.W dllllriilig SPCiTi1d1lilfcrenliQIUOn (U, 2.2J piRNA"'aiIIt~S(l~s{l '10.a. wide varie~y of n'MI(}{illcll!uikiu ,iWCrO'l!mtl:ll~mai'~. ID:dl!lSiw~yil~ Piwi P~d"'~l'lnC' l~iI.NA!;: :tflt ~liaJttv:tl]y dopl!!tool of
lSi(!)
_ _

.. .. ....... - ..
_

~'"

~ -

....• _••

• ••••••••

'.

'.

".,.

REVIEW
;jkr trnr!sp~Q'~s, @!td ~~e~ S!'!.Qi\'V th~ 5tKmg 5' U pNlbNi!we !w,tedfq~ m;;l,'N!q~<l!'!~<1!!] ViRNA:;; (S. 6,. ,/ 0,~n l~xmtms:1, AG03 associales 'MrUh, If!JRNAs slro'llgiy b~9.'i);~d m~ l!]a(\l ~usc :snrn.tlrn, of rn.:u~liIS and wiinb, ~Q 5' Ill!.llcluolid3pruf~ ~t\~W~1.'l I'). :piRNA~ ril. AGO] ~](]\;V ,i:'jJ d'il!lt.!C(5., I!~n~u(:~I;;i~ion w:iiOi p~RNiAs ill;tnd Wi AII;i'b cQmli~~, With Ilillie...e S!ll<1n RN'AJSO'v~u1a,plp'i!fi,g p~sely 10 !i~:a~. ~lteir 5'ell& (P~g.,2A).Acoo:l'dil~ly •.'filleAG03"~lm:d.I)iRNA.s were ~~g~ I)' C111i'L!ClwdlrOO" adcrliil~ a~ position lO,. wl~jC:h,

~r

is !,}fm..,km~n.lruy
1[l(iRNAs (j:. 7). ~i'!'Dl)1:1ce ,of [,\-MOI

n~

Ito

~e .S' Uof

AllIb-bo1:JH
PooI'of IPJlmary pil9NlA:o
h(ii,ii1d,

'011lfiL;lr'l!'Miol'lsiiI1~l~I~.d 11)f,lJ disli!'Lct ~mNA :r~l!IhUigrn~

to PliJiIi

'Dr AJ!jO

~oosib~ywi9~cl]~ffere~U b[\lgenesis: ~)OC;!~i8ms, .md Iedllto ~e 'h'Yl'o9~,esi!lllo: cl'm;lel'-dcrivoo tm~,~ st:ripns M(]I mtIl!;;cmiPIS from acli.vc 1~~roIL" ilfltm:aellJ:trolli~h ;[h.a 9.(lcion of :P.~Wip,roilciliL~I!O form a qydc ~~irl :aJ.'I'II,pllfi~ plRNA!!! d~:lIJt target <lcllive n~bir·~ ~1Lm1~~L'i1 {5).
The cyclic (caUec:W lllilePiB~-P~'1~ an~p!ijncallio:!~ 100'1') CF~g.2B)oo,gi~l!Sw~tEl. almJ!lsp;aso~li':ieh piR'I\1:\ drum::!: ,giVi.IJtJ,risc~ rIo a variely of

l;i!lRN.As.. i!~ll:noosl~lmtcrs;. a.rJII1OOm,runllifle:mem OlflmngpOSOlil1 fmgnIDUlts weuld i.fJJlmiaUy j:nm:tlloo a 11i'iIi'!i:lti:l'i!il sel~&e :lnd~iIlt~~eil[ii('l j;iiiRNAs, HIt.eof ~,polP.l1i!lgriwi1!!f!dI A!.!b. Wti1~!l~l'IOOI!,l!!tIi;l'" ~ng <l; (lOltlplel'1l'lmlru'y~, !I.In!!~r! !'!ill;,NA, l~iwi/AI!!lbooll1iP~e'Xes; cleave W II] fOOl'll 'ille ,S' 0 end of dL!'}] rassOOstedpiRN A (61, 7). lh:is not (IInlyi~aeli,vatGSl, I~"lctaqjlct bUI a.lmcroa.~s lIlle 5' mild of I':lb",,\'l,i Af'rt)G-.assoontM plRNA •.LoodM
AGO:) CO:l!IlI~(:X~
,ilJi1e ~~'i(i!,

~U

~,

-.A

'

capal!)le ~f d~vllti,g

(lOlTlpl1e<J:l1enlWry

wc!Jl~'Cls

~.et.j (7)'. orne pl!iloe f:lloln,M]J!ch OO!J!rj be deli vedis Ul.'CduiStm Iil~em3' el'lidi IprocessLng amldi mQdijliC;;l,~IQIl -

selves, CICl!iv*~ of 'C~lli!tertmJf!sCildu~L<l AGO] by woold thcngen.euatc adl:litiol:'lfllcopdcs of .he (llri~n:llJ~ aililljSirnl~'ropiRNA. Wlili~ch wooM. ool~er AlUh am:looMlu:: a\faii.lah!('l~o srllietlre n!.Jtivl]U'af» ~m..~, 1i~~ c(J\~lbinati(ln, (lf~l~e ~~ ~rb~11 a oolf~n~Hfyfu~g [oap. SigrI~l~ (Jiflli'J<'lINpU.-

fi'Cad.G1O loop are also

1!pf~11:

:~.

zeb1iafish (19)

and tl1. ~uma;lImili~n~liCpOO!lil~ne :1lI1RNAs. ,(1~, 'flInslmllsposoo .• nmnciugpallli'rway, s with ~HI, ge~!C>tiiCallyIilncpdecil!lndi ad3pd'l,l~ 'oomp'(HoolrulS, ~as mar:ry. OOJlCeptlt!l8J~ sim:i:lflrrlJtl~ to ,ada.,ptive .. IFl1IlIIdin.n, I?i:wffi Plrot~i!ilsal~,dl piR!NAs

"ig. 2. P,mpElrties imd liJiO!JelllleJj~ of IplIRNkl. (1,)

Feld~I!INlli;

of .Aub- lind AlG03-a!liliOdiited l!lilRI!iJMIJI

fJ!asCfJ.hlfD. Indicated .i1I~lhe! Si' U bias ili!,Aub~bc'l!I'1id p11mAs. tlliie lOA bi~ mn#II.G03-oo!JInd piRINlA.:5~ lhre S· p1i!()$phat~,. "!lIdl th~ 3' O·!1l1~JIt1!'Il(i!l1. (8)1 Pililg·Po~~ m()d~ ,~r plRNA m(i~nil'liis,inl D.to;Qphif(A PrliimiilIJ ~iR~Al>llIre '!Jlmeratedl by an Ulllltm(!IWWI m.edll8,rnilooniillllld'.ll[ll' iilJe miiltmJ.a.U~y d~po"'lited. Thooe:m.tiIir Qlt;llrgeta~ spedtkaU.'y' al"!llp~iAlIl!dlrill aJ SI~lller-d~,e~d~liI,t kliOilP,nvol\fl1g A.G0'3 ailld Al)Ii~\ ' a~:ld .~hjg:My enridln,cd:in IrlY'!lny types of 00· peuti:vc ~lel'l~millS, ~.Il(fludjifilg Il'Il!Ih1iplcftagn.~f.li1S o:fm2Sy. ZA'M; :lI:\'!'J . .ltlefllr.. 1njlrll!'ll,(l1l;C(.I m1illlnJ,tl~. mAtI~is ~:tef'l.Ooo.arad. essooliaiUy aU pi.RhV\.cs deri,redl frnrn this c:l~~~ .ii!l\e I.o~. I(J). 1111!s, ./l(l'" me!tco ls ,iilJ~ <1Whel,w<!i! plRNAcilJlsler ~~d en0Jd'es a: sp~ia\;~~,ellci~i1g p~m1i1li, wM~h is

I~~

ceUs (&), Th~ {lub.r:rglne. p'JJcrmly~ ~"semriMes so-celled spin!clJ~e..c:lfiJSS I:l'llUtlflnl£ thail ,d~:monSlra:~£: m('l~oli.cprog,ilSsioo def'OOts (101, 'fhl! de:rlilct~ ]111 sp:~lfId:~ ..d8$~f1IIilIJ~:lIJriil:S ·8J1fe a, direct I~WJ~OJ!l. Sll;P~I~ observed .illlfh,vi muCQ!~5e~II;!ei!100 C!~l;~~dl ATR (!l!,<l!,\,d". !;!If W!1j~1~;:aJ*(I '-I i').O~eli!]e ,gf !Wt~e,~oeQ1fl1esftQm o g!ecl"'5i>l: !]'gJli!lll~cd <1nd :R..i_dl3·.!'eI<1h~Ql) k!!'m5C ·cIe.,. :iiiiYdlJ:c{'J: knd t!1!a!; 'e.'o1e!1,ooHI~l ov« s,pec~!1:'c gf pe1Kient 'm~iQlic c'heclp;iit~t !i\'Cdv~niQ;ll, aadjhe ~ll<n~OlilS 'il'l f1iies.T!Ille j:r<l.fIUt,II.CX) lOO1!ls ~ pmed by~lng into jifilQlirvidual, 90~ive sl1'naU pllCilotypcs .of (mh mufintls am p •. ialiy &tipI;i!lresSes ImIlSPOSiUOlll of ill(; renrotmllSpooollS pressed.in milnals doL':[~' f:or lfuli~smvd~la1li'u,}e .RNAs dlJ."iI.~Ctt1ldmar o:ff'ect$ 01lL 100i ~ocaIDd. elooID~J!'; Z4M. ~.ldeJix (28, 19) jl'aI:l'tCMG'tJ 1'll3~ \!o,iI1(l1Tl:: til.d.~!¥I10m'l':;. !~O illL): pericm~ln).lll~richetcittll!;l1ilfl)ma:~in m~ 1IDI.ct: X patlnvay (3./). ln ~.l~.,Cb'l,.lM!!ofindhfidl~8J~ f\iwi Ilrot~hl8 d~~!1i1(!!oom~,Qlll!l~iie ~aly.sis f:.1t~~ I~O f:'!;iv~1 :l G~,ml:i~ ~lKrdi~ ,af Piwi rltQct3r.t:ru:! ~@:g~~ cause.';:! ~~oog.e!'i!C iU:!iest {UJ-./J). Ii!'! JlIlh!rj !mvol¥~!U :hi gem11]~le de,vc!lQPI'!!C!'ii1 til bodl f!ro'tet!'!~oodi~g ,ge~le I,:Ind~ly~~gfl'tm~'em:Q I\mcliml :,hO"!"l;l'l,~er,Ihe ,cl!~Q'yery ,dial j/iml1,el~w it:l!'I'I~I3b:r.:treslili!lcl, V1e'1:lCb:Jim,s {8, } (J-J2. 30), IliMm!!lts,.s,e~l cells are ell~ni!i.aledby .apoptosjs aillie.!" d1e ~l!lJ?~oicl~rmJiradi siPCml1l:ljdl slage (10). .Drosophila piw! is: r.cqJui...-d,i~~ ~e;r;m ce~ls, as is IllllilJOli pi:RNA duster pmvid~dI a Illol~l~lar Howe'ii'cr,in .,~J.li(JJ)!amcli ..MiwiJ {Jl]llil:'lUimamtlS, n 1lJ,H$i$ rorim abiilily '10 ~~ sevcrnl In:1i~I;aIOO; wem as in. SO~M~:i(; ~e ceiils, ft!rregn~a.ti'oiTh of Slladies of ~m.N As hll,lve fIDilH1ioo 10 a, 'OOIl5ervOO, funcu,On i'll. tlmoonlwl of mot~.h!, g,;;mcui£ etc:linCilis;arad Ith.i~ con£'i SHmt \oviill 111m :js, d~f~clJi,iI~
IrelrOO;lcmci~~, jla.hrdnm ~ns at l~ ~00 ~b
1

ool1di\!i~.Cinl :lIiild miillint~naiilce

of gsnnHnm mmliil.

~~h~t' d~r~t'lns a~~'i

~ioo:;;

ls ~lI\d.

REVIEW
;:I!.!iQYf!,gJ '~H.l~5,.. .

iilies halV,eyct been d,et~wd {l1lIwdeo;fllitac genu ~ine, 'Ull mXlO:i'd, wi~1IiI Iilllc c:l:xprossioflpaltem of

~~ep~ll!y~!!!e ~t,'lg¢, !m! ni~\'l., n~1,1!11~ !~d ~e:'ltIi~rllSl~,nQp~eWlQl),iPiCab!Ilormal~

11!!~iQn Q\r~[")"g~u.RNA-'I,i~ r:[!'S~~,,~~~d

m~!;mll!w;;~,~ ge!"1QlM

hm i]!e

Piwi:s,

.1\ k:~y qi!i,~'i!t~m iswlteth¢i' InI~~div(;lti!¢ ~ff'~cM: of Piw! ~tJ[1Il1a1~(1I:i5 ca.D'i. e;jo;:plaMI~d :i}01~ly be 1~lIliro~gh the: <lctiO!~!J of P~wipw!e~1i.5 Wi Il!i<i!l!:? pO&»~ cQn!rO~ Oil" whe:Owr odlet Piwflt!llCtiol'!s e:l!:{s;n~,[0 .J)Jv.-.Yp!Jila, studies (lffl~~rikl. d,~ al'ID on II.. iC(!rpmteilh, (3SJ D C'm:L'lp:ari,00Il3 to, ci~io:w.!> ~vtMi~ t!.lat, . .rnilmulli tC'ii~esL ~;~llIk£ld, .. IrilllSpOSOU acli.\I1UiQi~ 1:0 S€iv~rely i~1paifficll g8ri'lcl:ogene$iS, MU~il,]i~ of a :.'>urni]itc .('J"voll!ltioUl,. d~c:·oom .. I?awia:ndi pilrNA nIlllC~~I:1,er)' 1~(iRNA d~:s!~[~ jlcmW!J!ta, ~J,!i~t~ir! .d'e!rOOt!~iH !l1ay I'lave .<ldop!;.OO. ooth ,d:irrtri;,'fI~ s~FlU(;gi~ FoD' 1G,~~l and fo.Uic!{l .cell ~CVC~OP!lle!!t1!:!'!d1 OOU1~ !Woouc'ii!l!: OMld Iiltc!'h~~~,Jl11iU RNA 1!.rigg¢1'8 :,1 r ",,'Ut,) . .J'~l-Jb.!'e_cc", L 1. O!l!:J mlL._. __S ,,(~7\ '~fi~~" :1' I' ~,- lam ~ 1;'l_6.e s.e!'! :at!~ddHfereRl!: slrate,gies for l!~~imalfely silene-

d'lt'ol.!lgllil illtcmCl"lrons 'iVid~ the ,old lil"'-lCili'Onll'dl.eru" gtll1lm:r.ul.1l1~ sllllall .RNA!; dlDt Il!m~ :irmu dlis process ~ooiJy rnpca1 sU~]lg"irnl tlrLri!,~ c..~ 'by ¢tilt1:imia:liC)l'i from '[h~ It~\I'!.y rtmmi'~g :liIId Ei~~riflio":;illyacfhl'l.'; !"fI'le!tllil)lc!~iIL~. DNA ,~Ii!tliliatiO!F! depen&~'~l a~wi pro!ein,. "fwi!. Ibu! u!~!ike Ilhe case: '~ri. 'VeI:!ebm[es OlndDro-$'{)phflcr.

,~d !lu.b~qllle:!ll!lyfi~I.~Nd

<"5 'IlYl:J~v~~M:tQ!.]~ 1!~:!!rt ~QCOO!\~t w;~h~iP~~!l~ hW~,efS, T!t~ ~iwi and ~lRNA p<!thw~y 1111!Y tlll.l.slmVCl played a.llo lilg...sumding 'Eludi~lporta:lJll: ro~c ~n iuainmilJiiilllg spooh:;sC!:llieston by allowtl\g adiaplation of poplLllaiiOii'l~'i to fllllW I.nob~'lc;
l

~h~;ifl1~iiit.s. P[·G"w.N-'I'Ii.n~~rodllt.«iv~iMiilliiO'JJ1. Iti'ld! R\'lre~m~s~lild lNotes :1.. N. It 1'~1!:a, L, :~h~l!iltTDr,. hWt (It.em. 1m1. 3, :~~,
(:2001).

i~lffiled~o DNA. d!:nt~age ch.eC:kpoin[, S:~g!'l<iH,!,s: 1~lIlmis::probeM), .acln,vaterl [na,re...,~:re 1:0, d'oMblb. ",!mild biiCaks Mdsiing fl:OIl'I '1ra1l:~iiI 3CI~vil.y

(31).

'~11 Ili'I9I:uD'l'I11I15. g.@ml

CIOlU.!t)SS

im.. MiU amd!

Miwi2 Ittlllt<'l!~L'l: :has beel~ (',(I!mlM.od wid'! !!ro!i.,~ lil'OSQ:!i! 1Jdi\i'1l!lio!i! (/2', 16). O!~~~:SIJli!diL~ ..Ise sUjfppmt Ole 'id!C3 dll>1.t severe delbons ~Url~] ce~.~ dL':Vcltopn:lmlt C311l be a direct COIlSeqUCJ]oc of 1~ii'3j~I1I.octivai~ion. For leXain1p~e, .Dfm,dl.~

ins Ulrgc'ns. ~!~ D.~!(),~ophim, Pins·rong :~u::lde~ i!J~e sDrougjySlllgge~ .~postnra:nscr.iIt'I1i'O:Il:il1 OOlilllp<'J' UCil"ll to 'l:riI1iil~'Q.S:ou :!lLicnd.Itg;. H!O<wcvcrdliCt'C' is ."1100 ev:id('ll\lOO [{[Jlrii.np!3.eLSlD,f .Piw.i. ~lrotC~i!L" .flU 'C~II!iiIln'U!~n !l:1a1L;lS(36). I'll man'l!TI!,ds"Piw~ pto~ip!:S baw,!:: beer! mlpt~cam.dI'UI! DNA m~th)ll"!A;iOf! 02, 16). .. fUllOtioH dla11i may be C1>lf!!100 ,ei~er

!l, W~n!l ~~ ¢~~(/g 3':!'~, ~.i1:(~g@6), 1 J. G, ~i!J.v .tl' at GN lIt2!J!, l!.l91 t!O!l6). ~. ~~ W. Reddi!!n" N.lO'WBiID, J. lit )1'1 mrn~ " il!!iTIitil1l ."" S'I!IC!II!!zI!.lV,!lr~lIiID\~deM,~ l]~ U2:7(20OS}. 5.. J. Bft!f1nf!{~~'e'l aI'•• (~11.1Z8~1!J)I!9(20;0 6., It $~~(lft (1/., ~fl'te; ,1Jli'Y. 2iO:. ~2~M (2.006). '1.. l.. S. GWi1iI,'ilIilirdilM III S:,im,',e ,n~,l.50B7 : (:200')'t 11), N. 'COl;.~ (iI" ~,~ Ow, 1:2, 37!!S ~l!~9Ill
;1, ll;,

c,

n.

m..

a.

9.

s. liJ;J:f,1.~IIH"ir~9l1'l;l1
(2 Dol} .
I

# ~J'~ medr-

Ow_

l'.M, III

Uk W. ID~rng.H. ~~I\\ ~Ii'. CI!U ~ ~11.9 (lOOO). n,. 50, KI:I:r,a rrrKi!C!lrI,Mi)'ll9ilw<l (~ (j/~ ll,2ilt1j'ilI\llr.\~lt 1311. 8,:1'1' (2004). . li2. Ill. A.l.'lrlll.~I.l ~t 11I~ Dw, .(f{/ :12: u 5·O.~Wl07l ~~, ~. N •. c.w.. j\, II:I!!ilo, It Li~\, l:MteJ'IIlme-nr lD;27,. SO:l (:200I!il. 114,. ,!i, $'H~rn<llry, 0. ~. GO~, Z. W,~~, H.Lip·, (~[; Bi~. is,

d1!1'OOUy o:rilldiirrootly.

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pf>!]vi~llil rnSup'piIlIlrtingl Orn!UiDi!!.M'Mi!riill.

lil;atefi,als imC Ml!tl~d:!,
"i!Ittle< @n ~'I!' (~~111~~ SO:.\!i'T'm ~ere~~ M~5)1

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[lnd vieUi:IiIJllI[lnljJile of a \lOCI 00 Il£lIiIiIElI'ilIl (rE1!ll11fhe IlIIlIit'i~mpellm 1iIne upper.D oi"1MIo iImeulBil 'r~~ The:'~~at1h~ dl~l~md'is, ~g'.~~:_ fu.;h~IP~~lrO!'W~d ~h'lhe 1!l!!JS. (8) p~,~~ 31 daisfQrag!f!g~d:c/iy (G'm,t OCl~ ;001 Oem_ill" 2(106,;5~2200 6:44 p.ml,~ _~ 521. l.M! ~00Ia~ was G!lilllr~d tymro gro!.lnd.~itedllrJ8(eivel5 ~Rlill!d 1R2~alWF r.lmt"lg: ItiitiiJe ~aJDlHii 1m !8naH:lIl1dII~;j ba~ingl(l,ftl1e 'Ijr,d, ~.~·I.n IlIi:llll'f;fillel'l~!11Id ~l sha~,gfwgPllmm* ~OOlrlsdtM'Sl:J~OOfoIfil l(bhE~ 1l00ld.1 '~d) me'llieeo shoot\fJ:Jeo.reall"dedllbehfi:~ Garl be l~ro. ~n:lll~ tIBjedmy (see ·fum v~:im~ ..~liIiIdedl.al1ei1S ~llIdicare ~,,[lnd 1rees.. (QI,Am.!ityprOIim m'Mi'CCl (pe~relillnge Ilboom,obJradMity in mi-$ '1fumIe: blliis)turing the: \!ld1oo :sho~ 1fJ:! .", 242 bi'tis,'wiih 11!Ini1-.d vkIm reoepiiorn). fbod.·itEms i1 I~a~~ WER mt 1il0itlliilft(jJ_ ~D) iool.~ grool'd {eragli:g lliivill VtiJ)(J a'0i'I (EK1; :ll7lkEimiJer 20iJ6.; 3~S6 m ~:O6 p.m.;: moWet S31. Irmge'> stJM' al ~ooI.~Mtr rnin~ill1ldl (r#§h6 illEr <!Ii long llIJight ·(I:Iote· d_d: ruM!d~'p). IFiig. 1, 1(A~I~f~

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.;1001

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:[lO.1126!sd!!11~l'!.114,6{89 IlIcllld~ ~Iili,'im!mma~oll 'l:\lhe~ Citil"l! Ihh

poliptr ..

!)ep~r~!'Il1ent 'o~ Zoo~Y. IJJiliW!rsi\!fo~Od~,SC!uth ~il~l!I, !lifor~ Qln3PS~ 1I..ii11i: •. Q

·~'o ~hllflli ~!lrre:IjIDOO~JlI(;l! :!ihlooldi be ~Id:llr,~d dilrisliallLwub@.21OOIOo!l: ..i!I[.uk

Parks
E'I!El<lil:

IQuan'lum Spin IH81111 Iinsulal'to,r Stalls in HlgTe Ou,anlum 'W1e,lls,

Mil~klm!l: K:oo,i:gl,.1l5~effen 'Wi!Blfrrn:ilIliIlll:, 1I. IChri~topb IBriUtfle.1 Alndll!i!!:a'$ lo.th,1 1!!l1I1fiI:m!llI~: BUIil.ililllil".lI ILIlIUI'I!!insW. MOWe~m:p,I'~"Xiao-:LiilllDlgl Qi;!l :Stlllll!l.Cfrll!2:l1Ig 2li11i1lllgl~

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~aycroo !MCiI<lIis at higb IfIla~lletic
flt':klS8lIld, il'CSU~~S fIioJT:l1

-he ,dJiSIOoverymofe II~llir:l 25 yearsrugo of IillIIC qU •.mt1l1ll'l ~9n efffibcl U},in '\\\h].ch.d.u~

~1C(!IfeUcallytffiU1:~ Ute: c~JoclD:on;[c stllKlMllre onnverted ~gTc:qlli.l!]l1~ [!lI1lrl wcUsexhilbilS d~c liircpemcs, il:&1.a1h(n.lM ml~1b~calii. obsel'\'Sl.km s
of 'i.hc;~;L1:ltlu!jjn

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d@"((lbp31~~!m

ciaUy d!~mooh lboca.u!reofdre vel)' ~~i!]l1Il vo.llatil~ly of Ag. Mn:roov.cr, Q.U:intUIiI1I i[Jol!.!n."Spil1! ~.umk.r of Gdg,Gchannels ~IlKIm ,san). w~ 1.1.!llvt: d~~~lopoo.a.~cial1owWf!n 1cir!,U!)e Gi3!r~ie~5, d9IDOcsJllim rull~~(oo Si,·O ..N ,j(~ dh:1ool.1y rul!1LtOO.lu dJl(;; v.altl@ of is 1~IiI~qj[Ja:nnurn H~I[ (uldI!.!Na11lCC:., M',~ c :@~te hh~ail:oF (.7).. wllch a1lo\l$ i( Schemiliti of tile sp]n-pgl .a.:r~~d ,ooge ch<lll1lnel5 1111,[1 q:~[lntum spin H',aU I!.!S I~() 'cotllroJ inhc Fennitevel I~n~ (!IlVCr,.Ute d~rge carriers i.Hdl~C cll~· inlslll:~Cloor• ~e18 <lLu:e vC'Yres~]al1t to, !>Cal:lerb~g. ew!fgy level 'liP ~o\'l,flich <III. Nol: onlyc:rul the (j1IIDlItlJ..U:t1Hi.lU elect be o'bscrvOOl :UIJIIMa.crosOOp'L'C s<IIl'lp~:€S elocln:mia> sta.lI:ii are filte&) :kIldlC ql!l!llL~1lUWwolllh:ml alc oolilclldolil. 'bruLd. tltml!l,g'h, lll~eillSul!tltimg gaPI !!II~d into {he valence Immlndl.Usimg boIJ]~ dOCIrOIii. fur lb~~ 1:'C@,";Om\. w~'liln 1t1~e clWllilels, dgaa:ge cam.m C81~ be: tlalc~o::I bl1ll bemn ilnd opliC3J~liiltGgr.3phY1we have fabricatoo sil.wphll roclBllgular 'wi~O:-i!l1 energy dio;..'lripatkln. TIU1:rel':"oru-,qlllailllU..lIl.l H!lU. oog,e chrulileis may 00 SIn!i.Cltli~ in. 'li'iu1O'!IIS SlIZllll [man q,llflnllnn \.'IiiLliUsr.f V3!~l:Ig wkld~ end ~cffl!lI [Of' ,appl~liofu~in ~n~:egrn~oo. lttU~1 ItachmQlo.gy, \'il:lmm pcD~"{j' dis· c sllJatliol'! is bcconllU1g 1l10.ue Ol.ndrm:rJie (Dr a f1fiOMii:;ln deviCC:!!booo.nne sm!!1tcr. !llea..lllfed dle OOQd~c~oo as a fU!'tCI.ion of ~ yd~~, as We ,ooS'lmlClhal :saH~~~~es ~nRdillrrom naa:'OOw 'qj,ruJlnUWl ,,",'CIls wi~.~ a oroCJ;U_I'SC" ~ero Ol.ru:~Hror(Untttl~'bleohs~adesto Ove!'OOlllltll-'the qUI;mM!!!ll "I!lOlJlIlkl~" elcooln:m:i:c: struchu:e'b1lSLeally :sham 2.e.m ,ooHdruc!illloowilelldlc; HtlU. e[fOOt:c.uly OUCUl'"S ar l.owlClllJ:naI'alnres and high u'Ii.l!DlC!lc fields.. fC'nni~e\fd fs inskie l(h;e gap'. 'Qu<l~num wdis wmd~ :Il.uinverttidi c~lecuxndc ~~nlh.e pt!.'l:I:fcw years, l~llilcol\l2tocm'lpilysii,cis~s ~f)'I!\e SI.I\gg.eiSliOOliliIat c;dgiGcbmmel. trmn.5po:rrt @f'0"lIIrrcr.u mig:bl be:IXl$~bh~ timl.il~efl,ibiSen,{l~ of ,8J SU1.u:cI.llrre,. tty contms~, sho~:v .81oondl.loli;M;"fOO close 10 ,lO!ihla~:is, e.)!;poo~oo.rQ'i1.~ei il~ n.lagJ~.elicraeld, fl'my ml!'lledi.Cfil,di~2-4)1~ffill3it~n ~IL~tl1lators wid~ sui'!aib:lt:l edge ch3l1J11e;lmrnil'l~:I1D a qUi!lnliiillll spin HanUI!I.~lllaMr; 'fhisinmrprelauoJ1l. ~.~further ~01fili'(Dno:malb""tll 'by' magile~omsi(lI.8!llOO dMtlJ,for e1!i:ail~,le, high~!~ctroil1i(l .s1:n.aC~'nIDL\ ,~dg!lSI~Mes:!t¥.QlIC!:ld~'eVidopwffilOO1:-alld Ihi..to:i is !ll.OIg!lcl:ic field, ~ GI! 5a.!I:!p,leswJiIl. a:!l.~f!yerted, cleotronit~ 54l!r!lIoturesl~owa d.iffer~mtli:1)i!~l ~Je ql.mntum :Fl!<l:n ·err~ot;-t~nl Ca!iril.'fS; wilh: oO!p[IOsilie veryulutsua! flnslllla~or"rllel;~~"h~l:Jil!.1t(!Iril'aJl';)kron .iilS a fimcd.(l!u. o.ffield. I SI):~UlS!liI.(!Iveil!l OiPPOlSi~~ dh:ectimall: O~I a gh~el] edge, as :shml{1l selic" nUit'Lcallyin thefig.l:ll:e. 1ihls:is the qllll,Unml sl?h~1Ha:ll effiCc~. and U.s wh:i.ch, we demonslmte isa direc.t conBeqlll.cm~e oifil}c electronLc SII:PJC.~I.Ife. (lI:b.scrv;at~;Ol'Iba .. been hOlly .purnlleJ ]111 !'1m fiic~d. Th~ sp1lil"pola:l'izc di! 'O\l,amlcl:eii,ofU:u:; cdgG CIl.!I'llIltlls SliiU. In.ced~tok liIneq:urooc.'ibly d(iialOOlSllatoo, Po:r "PpUcmio:ns or ~I~(; GWOOlil~ 30Illil!. Aldlollig'h.liIlI~roaro mal~yillLwla~ol:'S i:n.naillro, ~n)$t)1'fl!hl!i1iitl l1'Gl ~8iV\C ( 00 I~im IIligh:~S'h!3~llrulp.rope:i1Ii~ ~\l!,~~lpw I.hequllI!Ihrim ~IrI Hall 1L'l1l:'~1til) 00 1:I1I:aoeI.QelruniCIlM:hUB~lo.gy, Inhjsl\:iJ,w.II~~a:~~ru ~tfl'lCt (W~dbSC1lll('lil Q~e~~. Thi<i i~ .. h~lIl'l fI,gTe O(~ v i.llc.:BIli.lk HgT(: is 3.11·VI s~[j:l~· b~~Q\'" IOK) 'l-vinhil¥¢ to 00 d~'i1iOlil:jt_~d.M~m 1:eI:n~mIi!J:~ ,)!iihich. may be po55.~b'Je lnwc~i!s wilh~'ViderlP!p:ij:, . . crn.ldU!c~or~ool has a pOOl.!!!O!:f~~eci:ro!l~l,c s:lructUil'e:1 u nlQS~woll mai.eri<!!is, ~lheoQn,duocHcHR, bawd, m~mlly ~ri.w,s frorll! S"S(aiesl!OCElle4 0111 nlegro~p Il ai.Dmns,ITlld ~~c v.~l!elwe bIliUlIci!f'rolll p"siates at ~~e V:I atoms .. mil, :H:g'r~dlis S!!!!'!'!Im<!!ry Re1'le:rencn {i!lrd.G:'~:!l ~va~:cd. i~lrnl;l~Vler (5),. Using moleoular b~amepitIDiY, '\W can ~. t:;- v. ~i1l:[I1~ ~ lil'Oroli!\ rill Il\ep~lI. P~" J'1et'; Ut~ ~,5.,411<1~19·~()l :;!. s.. ,rllruraitaml, N"rI.I~!ama, S,.(. Lit)2f1'9, ~",~ei\i. 9"1, l.5'Q.M!4 (:WI!J;:I~, g,I'OW thiliit ,!-:a.gTe q:u!l!lll\l!m weilq. sandwieil~iIldb~lw,LlC:n {Hg,OlJ[e barricms, ~. (. t. ~~~, E,.JI,./l1!!11!, ~. ~ir.. .~m. §, H~Di.;l: i(2000), 9 1~IIil~lolT~ra. ~11.iqtl~ Wiil,tQ tillme ~l~ ~lG-Cir{]tlio:ll'ftnDCI~ oflh~lnal.ml:t11\VIum ~, B, ~. ft~~iIe'il~. 5 ..·(, Zlianog. 1'1Jyf.'. krl-~. l,l!'Ili:. ~6, lQ\f8012: W::~61. I~§ q!lla:IrIl!;il'il "\i~U.is wid~ih¢ ¢1~~~1!!i(:~~~i~ itt! d~§.W~U ~1lr!i.al~:I1!i 5, A.. fila-iii}:. fJl M~ fJlzy~ ~ ,1:1 1',2, 0'3512:][ ~2:00i~l, imrert:etW. :How,c\>Ie" tOr natrow~?fCinS, i~islXlssili!e·ru. oMail1 a "rlQrn'l<lI'" 6, B. ~. 8e1flilllrl~, T. t Ii!~ghe,$" S.~, ,ZI~II~, .:iil'irn~ 3lil4, 115,7 (~006t 7. 1. ffi!!llei m,. Semi',OJiQ, ~i. Tedil'td. :21, '5:00 (2006\1. a!i.iglfilUCJ1l ofU:te qlJ<Jn~llIInwdtl stWes. ReoonlDy, :Bemev.ige!aJ. (6)prodJl-ctodi isnic of ()[tL-"'-dim:cnston.<L11raI1SpCII1't. Tim
ICo lfMlIiliKtaDCt!
,cnal!!)!'!!E![

(!lInt;)!' ilIlmle dJ~reclion, cx~~bil:s, iilql!<Ji!la I~'W!CI,oon.dlll£l<ln,cedlQtiscltaMCter-

suff'iciootl,Y ~igh c:micr m.oMII.ry. co:mmumd ..:.nlt]t 1ihL'l IJlIDlngmphi~ mool~niqjues!roooed tD ~a:IIMl Ure SOImple.']1ile paUt'fnilDlg is: esIJC'

wl~,1iI

1'.

RESEARCH ARTICLES

FULL-LENGTH ARTICLE
IRIl1.(!M,t theMY p~,dffided that the! ,q,u.am~!lInil ,IIili! tlaU !il!ff,K1" ;"ill flfl!il1dl1n;1e1maUy IIIUW qlJ!ali\ihil:liIiIl~te m: ~ Il'IiIatkli ,tha~~Jflm: a1 ~,I\a!' !I'!:~tllr~'l !'Il3!]l!iIelik flebll~ !in:!'!,Y' ~!'!Ihi!l'!d1 in "gTeI(H!J~CdJ'T!I'!' qua,,.'hlllm'l w~. bl': WI'! f:!'!bP'ii~gtl'!d $1[1(1111 ,~!inp1e ~fI)!Cllll;)J~ 'M,n! tl)1Wdef!$f.I:y' ,:1m,dl higih lmobilityrll! wM.:h w,e C!l)Ijtdl'tul~'~ tlilltlU~h tallil @i!tlii!JrtlililgatE' lItoLta9~.~e' ,(arnetl Wl1Itl'lmtium flroml1l~,pt!' t~ P"-wP@, ,assi"ngtW'O'ug:lll,i:llil tillS !!I~,til1lg regime. IFur tliiilil'Q,uarrt1ium weU~ wilih wel!i, ViliCiUl 0<' 6,.3 rnllil~mi~ell'S., ~he'ml!lsulartill!lgllr@giime' showed UK! ()llnvl.Nnio~I~.lbeih'Mo~ \I'~i£hiingty ~I~m IllDnd!!lCli:ru1looilt. 1~llwb!m!fleliilil:ul1e. Ho.we:vet. flOr '~:Ir"i~keli !llillllltUfIII wen,; (d::- 6.3 ii'laIllOmIB'lll,r'5). tlile loomiillla[[yiflSlillailllgl q A"l,gffime ~Htledll IW.i'li1tr(1a!ll re$idll1lal ro:ll:dl!J!;il:anc~ dL'l~eto 3ri;l.IJ1~!when;!' ill' is tliJle elecib'alil c;h;ilrge an.d! h IPlailld:'S 'IN IWIW;amlllile: ~~d 1[l~llll(lfildlum IlJlle wa~ ~!ild~i~lild~!1Vt ~the ~,mp~e widiOr!.ilildk:atililgjllat it 'j;s C\l:I(l~ed Ib, 'E!~e s:ta,t~~ ifl.!!iiIIl!e:!'!iI'!@!"Qj' tbe iJ;estdL!!'!~.oo!i!dy(tamoo wa~ d~stroyiMI bya ~rna~l ,W!elllid. ~!!Jnetl(. ! fj,ef!d. l!he· ,q,ul!!llTh'Wmplhase' traruitii(ln al Ule cn;fica~.midimless:. tJ ~ 6.3 IfiljIlno:mete:I'S.MS a1500 ill1lCiep!l!liIdentty de~I!In1iI!l!!l:Iflrl!1llilltillie' 1~I~nm( tiel~~dn..mdl iIlIlSlllliltol1·tO"'-Jil1Il!U1l.I!J:'iiIll5iliii.m11l'~.9@ l~bSelNiltiDlils ~IRWi:ml!!expE!riim!!ntalmdeliu;e of the Iq.lililrn~liIm SP~II!I Han 'efifw.

q~~!~hJ!m p:h@:.~ tr1!ll!shioll 'In,,~ @.~$Q OO~~ in¥e!'!t~~di~ ing

mllOO'l; re',ii1i~~~ic !illiOdeJ:!l.b~y~'!iI&!ll~ t

siaflil;l'Ie f()iUJ:~a:ndmode~presetnted
thC:S!'IlJ~C

~lere,reac'.~

(loneh:li.'>ima U.I).

The QSHpl:tQscooclLlr.l>~m dac lilverlioo m,_ S~I)'i~W~~D'(; M< ,[I,. i,~",wh$l~ tl > ,df?,+ 1Il:~~ fiai'llp~e,edg~~. ~. 'Vi~WOO~8 ii. d01'iflJi:lJ~u:'i wall on~e W!l~~p"!'alhe('.Cr M. 8e.p<l.!i;.ui,~ the 10pologially f:J.{!I!Iurivial iPhasc withl~/< 0' foo.n tlte ~'Opolqg:ica'~~y lIi,ivi8i~pl:bl1i.se w~t~~ /!it> 0, w'l~iiCh, is ooi.a:bmically eoiUl(l~i:.,j to the vae1I1!11111. (12). MJlIl!s.less ~~eliCi;J!~91B:~$ ar,('j COi1fll~~
Olt! Inb~(lalifl.lpl~,

eondu.,c!:~noeever! wher! d~eFI;'fani leivc1~ics inside the ~~lk insl!l;ati~g~:p. Therefore, as

!!:lII£gesteci:~n (6), dlft~ QS.H stafecauoo
t}(liI~dll{ll:anC(lpla~c.:lul as O:l1:[)varies
VQI'I1itg,(l1

,oo~. 'lhL;':s&rlp~'~

l\;,is aff'iniOO'

~T"lm

~1~ooro~i.mlprndi.ctiolD.

Inl~3.lil~d~li'Isu~.l'IW'rs [n .zinelbit1f1tJc,.:~yp~ sl('~ie(mdl!l.enu~ QW5l, lI.oc:ro b~d~ dOSifi: I!(!, tltc(l F~!]II:u _ _ (1-.3) :has:~~"i:era'l~~gm;;atiflli(lr~ t!lq t~]e aJF(:.fuul!'~lev!ln[ ..

:s:!"irn,Hall (\!tT~ctin.

of

ex-

perh:w.c:n.~au.y detoo~ed. iby ~le3S!llri n:g8i li'USidmd

I~m lij~lriia:lJl[e <ilii,mliOil Oit' lffiI!cl~;umlflllm1il1 SPl~l H9.1~, ffcct e (6), the gate

fle~d oW~~,illtOO!!licsj[)e(;;1JWC d~~8 cUl;.lc( ".]lZY"""8 di ree I ek~ctric !'IHm~'IJ!i!l.a]!o'!1 of d~e spi:n degrecs of flicedorn \?;,'i~illloo~: Inagtleli.c fi:c!dI., '-l. aile:!. t~~e I:c~:l1i 1,1gSpi~1 CllUiliCIU ean tlmv with~ nut di:s:s~.p;a:tio:lil 1lIC!ll(,: ~'ropc.rtk~ !)outd. ~C:adll\Q ..
~ool~.is[l'I;g :Sl'llnlm'om.ic devices 'I(l,!'Uhi(ii~'" IP0\''!!('lr

le~eL 'he~] 11il1!~dI m:~iS!~or the ~o s.p:irl slates of !!:hes m,ilii!l!Jl.whereol.s~:hc flH~.band oo:Uls.i:s~s flh,c Ip.., ~ illY' o ,HM:lIII'-{Px ~ ..I~PJ)'J)
orb~tocls. 1"1:te,elI'Ccluvtl: Ha:m~lt:mal~.an.Ileali l~mlCr 'poiml, thC!c'ool~cr of l~:hc Bril~ol1~111 zone., i:!! g.iv~l~ by fl~(k,r.k,,) fl

di~mpat~o~t
HiI)'i'!~ver,
bCyQ!Mi theiXlfenl:i<lil

ica I appli:catto:n.\l;, thei!1trinsics~i.n fu dIe

led!l!~ohJlg~ H,,~I erfec;(

=(

l:l~k)fr~~}

), (I)

~;l'!SW!1idoo, us in d'lil: se:flJ1'd~ fOil: afI'CW' lImd toliX'~ .i(iigi.c8i~ly mUDtn.vi~l SIllI:GS of ]ll@i!'~.er: h.c quenT
IM!ll.tI!. Hl'IJi st!l~@

== 8](k) -I- tlJ(k_)O:j

i:I~81!!1I.a:lil~~rugimc. F~I'I.h.emuOt:el b~~iU;I!~Ii.lII;~ecyrnC!fl[l~ C<1iH'icd: by the e~~ ~ale8,lhe ro'!!dUC~m;N~ sl'l'O.mld be I!Ki,c,El(.IJldCI!1l ·(If sampl'e widi~h. .P'lroi!ccted by lite titlle..I"Cv,cl'S!l1 :!>Ylnmctry, nOlll!:13gncli!c inl~ purilie!! er 91~y Olllil('lI'li 1,[Q!N·C\,I'crs:!!lli1~villril:IiI1l loeal pm1I1!1rbami.ollSCSJnilolCSJUJSC' 'L::~3Slic baekseatl~[J!!Ig 1l'I~ ~l~~iea~. edge !lHIiI~, \lItlkb \It,ll ... of rant~ lffil,(l'[OIXfi~(I~~]!1ObnlOl!~il ofd:le I;ldlge ~ condu~ta!1LCe. Howe!;'Cr. Ule pmClilOO <!.f!l~· netic fieM bllCaks ~ime-revc~l symrnMl)" and ltloodom can open II!Ip 8. gap ill jhe cmmgy S'J?(')C;'

I~ Imlli'mnruni.tm.!i.y

or

~ll'l>'~~3illdi!iQF2Uih(l oOnl.)' t

OO!ldliCIaII.O(l

(l;l(3mple, o:Wa tq~,ologie3Jllyno~lri.v:13m. S~i.lJ1£ (If I!Ui1!tlJC["wl:tef!1: 'ihe ~uOln~:i:zalion (J\f 1!li1o(;:; H<!llool'I~ dl[.c~,~ isprO'roc~ed by .<11. tlJpdlogic.ui!'II'\!',aw·

Imit!Ull ~f 1~~le edge l>nfltcsllilld .rernoVll: lfilmresi.dual . du£~o t~!le oog.E> ~a~, Experirnlemtat. Id,ri!:aIU~. 'W~ set O'lJt to t(lSI

tl~e.se tl~e(l~lic<l1 ell ~ .M- ./'i!(k; + k;). ~=C-D(Ji;+ki)" (2)

p:rOOlctions by ancaSYII'Lf:l.!!

~mll Th.e qu.matllJ'uspin

H[llil (lOS-H) i!!8ui1ato:rs

(4:_6)hav;e a sillli~ar, Im~Q:~stillCt,.I~O:ilttlvfut~ Iwpol.ogfcal ~roperly., QS.IEI ill.'lIJI,a~'OrsJllre imv!lr.ianl. ILIluldcr time r~I/(']s!lI.~~ill(\i'(l l3J .Cll~Mgt' c<~il~lion g;(lpil~'I t'hcbUiIi!:. bUiI ~.<l.'!'!1i:i OO;pologi·

the trnnspor1! prope~tie$ of HgU:I{Hg.Cd)'fe QWs :!ISiJ fUlIlctitn:n, of Ute' s@fnp1e tffia k;lkness"

n~

Here, k~ a!,!di.li). ,a,re ~lo~~tWlta ill thep~tl;!ilc

c1Jilly pmlJooled gap1e1l8 cd~e stale!'! tID!;ac tie !~s;ide dl.C bUill< 1.I'oCsulail:l!!l,g Sa,P. n!is type or

orthe (wo-dJimc:n!'!iom~J electron gas (2DBG~ .• d\;:.). DOO'ica~m':IICI~li,!-idlCnl1lit~ bllj(!lgct GptiC<l:~01i!:td aad A, B. C. ai!!l~ D'ili!ie IJil.uclilal sped.:fk) COOlsDams. Spim ·orbi~:cmlllUnig~s nal:lIIc1lillyl'll.lihin ~n thi:s Hflwl~bo:ni,flJlil tlDrougffil. til,'_": ~h~~orb~~ oouploo. p rubilals 11:);.; +ip,. l} ruild II~·- .riPJ'). J}., [,w()·dlilmmSkmal n~almi,8J1ls Cl1lIil. be grouped i,UllO Uwe types a,cco'wiug ~O< 'q~e~i:gr~ OIflhe :I):!nc ulass!'"JJiitme(er M. [n w'nve!'lt~m~ .. 1 sem'tcona!Jl;ltOO'S slIch as GMsilind CdlTe,. ~'e S"~:[kleEI
'U81oo to Sti'iI!I.mlJ!lre d~.,5 in H:al:~ bar gCOill.lCW1I' witll dimtillilSiiolils (Lx W) of(600 )i;;~OO}.. {2(1,j) x ]3.3)1 (to::':: 1..0)1,liln:cl (I.•g, x O':))'fu~t2 (Fig. I A,.~Ii'I$~l]\ All i de\'iQ~ h@cW.. 1] O'·$!.m.-th~ck S~~N41S 2 n:n.d;0 tt~~ye:r ga;leh~~;~lalrn: (It}) and! Ol 5130 nmi TilA:1JI sate o:lecuroo,e :sta,cl;;"T'r.a!:lsporl!1!l~,a5ltl'em~I~1s

the: gml'lvolta:ge, illl~d. the exretnal ~lJil:gIn:O'I'i(l [tela!. 'iii.'; ll"'il~dmOOtI:l!mt&aIN:Iopcd ~ypc Ill (13) llgTclHg)],,jCd.r,):, Th QW struet~II:e.~ fa'bri.C3too byJllolec~l"'r beal'll ~piUt"'.y (4),~wui!h ,,,,~dd~ .. (J'.:ijr 'I,'@ryillglWo!ll 5S I~Hl {d< ll~) (Q12 !'!i!TI (;I >
c.lbe8ml~il'ilQgr~~y,\'ifiitS

~IilSIll a1~!r lSlyp:~ca~ly i reaU~edhl. S;p:tIND!rbh c.oop1ed. systal:lls;. ~hc cfu:re8pcmd:illg cdg£ stains ~,flVI.'l a d:i£i~i~.ethlclic31 pmpelty:ilMJJ .$ta~M,,,ith,

V~Ci3:\i

lIlPPO£iUliil: SP~rnl.-'polru:.izat.i~:n,C(l!]Iii"IIi~iIDpagat(\;

3:1

~ g~'i;'1~led.g~;{4. 1,8). The ,edge

Kfmm~!'S,' dooMe!S.
el~Sll!:eS tl~ecm'ssing

s~~~ cQ:!1le i,!~

ma,d! t[!I,le~!\..~'e<ml8)'m:!l~t!)' of Uleir I;nergy Ibvels at :lp~cii'J.~'lXIifrutsin til.;; ~h::mQ<u~fI ZQ.1iI'(l. :Became ofthus cn.,ug:y~,lcvel.crossllJlg,. InJa.e ;spOOlrlJim ofa QSH h~l!fl'llatorCfl'ln,01 b~ad!l3b~li.C3l1y d(l~ fOfl1100il:lllo thrut ~r31 topolo,g~eainy l!rivl'al i:lilsy!<Ji!Qr~1!'iltl!Q'~l' eHc<!1 ,edge ~,.i!'l.eref'O!Te.in h I~~b: I~!se I S'e!~, ~~~e 'QSliili'!lruIliU.Q!'S :!le'p!le8ernta ~'OPJIGgjca'nydiisiin.ct 11~Wsi~(e Ill'itt~er; iliHlUIflrtic:al lJ:ockgruYl1Id. I:l: laas been pro~ liilosl.1>C1I~oo.mtfc8Jny that .~gTcl(Hg,CdlTe l quaillnMt:lw~~~ (QW~} pro.v~dc 3..miMilLmatro-

OO'[D(Ilies I1l00YC: d~c: 'P"'Hk1,;;!iffl ~Jldl! (l);lld I~'hc

Pfll'llIl:tl£'ICii lIJh!iPOSltive."

WC((l

d:Oilt ~,n11iJ, ]lMctMc~dil'Ul,lioQll ~.frigeiOO.lor

or

tf1'ty~ik;~Ii~d!E'S IFI!5iiitJUt tEiP 1IIIlo, UrtiversU.il WW~bUFg, [ji-9'70i4 WiI'2l!uJrg, GE\r'~ !ily"zIDepli!fII:!f!'i!e~t ,D'I Ph)'S'l,C$. M((I[I~!ill!giln 8:~,AldiI:l9,· 'S!afQIOId Uni\!er~lw.St~rnJ!1ln:!. CA

9<lJ~S-<l!Q'4S, US:A.

S clu~"mclBl:; S"i!l.dl.as gfaphmn~ (9., It!) am desc,'l'ibed ~ya m!L~sll$S~ D'.traJCl1Ilod{l~ willlll1, .~rI= O. 3It(hoogh dm b<!'I1~ h<lvc <1 clifre~e!~tpl~)'S~c~J~!1le~~t~!k .. ]l. [!1sQ~!i!nedi!!lvC'rijed. :sefllicom;!"CIiCl!,"s S\!'C;I~ liS Hg"ie" ~,e s~like orbiitllJ lies below iiltle p~lfke orbital s; i~;herdQl:e., ~lI:!e:Dime m MspamllllCter Min the .~ gT,(:/(Hg,Cdi)Tt- QWs can be ClOIl· tiriJIjolID(>ly~l!l:n.oo.frQalii!:.t pm"il!ivt;l'i,!'fl:tiIJt;l.M ::. 0 fin tkin QiW~ wi~iliI.ihickn.e£1'l (J <: d~ ta 11 mu~,g,,arti\le:W!~ue 1"1'0:: 0 for lhickQWs wjiUi(J> d~"It lapol:O£j;ica Iqlll,ilII~1Jum:phasle ~iiol.f1si.tiGi~ooclIIrsa1 a criti.c.l1 th.icJja~ess d ,d"". 'Where the sy,s~~n is
,erroot;ivc;~.y dc:scli.lbed by a I:'i;la:ss~es!l D.irnc

Illa.~s

(l:1il:SCi te:ll]poi1:rl1hm~ l'..;:: 30 linK" ru:n~a...i.flt fields . up' 10 .~. 8T) 3:md.ii1l.il, 4HecryG.s~at fiued witl~ II. vCoctor aIrNagoct (T = 1A K, am(l :fields l\1JI' ~o 3,00 n~Ti~l Y.<wi<lJ)~e d.ir«l.i.Q!]), wsing k.lc~"i!il

tcCh!llq (!CS, A~ zefQg<!:~e voUE!g~,the jl~n~pl,es:

were !n·'~ype, e.x~~i'bUing cmili'lcr 4ensi.des b~~ tween t3 x U)IIIITIl~ 3.5, !O: UIU1 CI1I1I-2 .:111(:1 :1ltliJ~ up to 1.S ·xl.,OSam~ Vi !,-~. ''[he ,carri£f d!~lll~ny ,oouild 00 rudioo~. 'CO]lt~llil!lQtlSly ig:y alPp~y;ng a ':i:~g4t~V(lgaMy(lltag~ 'trl ~h~A~ ele(:.. trode w!tb respect loca!Tie~ ~I'l tlii,e OW. 11).(: Su~O·N S;ai.'e iIiS:lIlia lor s~<JJck~lIoW\ed oo'r quite large sate voilag,cs, el1QIllHllIgus to gate the

m~e.~

'Olio t~hlll1ll rorresptJllId!!IlIQ!' :~hol!llJ!l b~' ~!lIre5sl'd •. E-mail:

mllli!!iiili:liI1IIl@P!IiIr.;i~"uni~ul!if~!lJfg,d!~

s.rnnp~.~~ ~~lrou:(!;h g8:plfolln 1l4YPiil '10 IHy~ 1 'lite

cOI~du.,cC:'\ljjlCi(l:"

O~Mf'y as ['Or tfiiiP~(\,;ifl(~. TIu~ nalure of ~~~i!!

RESEARCH ARTICLES
~I!lli;l~ di!~c:~I.Y oo~~it!~~from I~'~e ~m~~in',~lCY,~ I'H~t rQbg~ly ~t~~d S~mlH~n~~1 coupling, of ~he siH!lple Di_I'l1';nlgd~~ iI)g from this ease, im;:J!ea.o;!'ngltqe!n@gg:l~.ic eXpCli"~menilS., as. SIIDWill in, Fig.. LA fer a. I:ru:ge fi.e4cl! slrui His the iliool La:I1Id:lilileve~. towa:ro: highoer (Eq. ]) to a.petrpeoo.i!ouhllt m~aDle~icfie M, lJlc. 'r(L )( ~P) .. (600 ')f: 21(0) ~~.1iI1:!]Ha.II.OOr wj~h iii [f;' we ~11I.~.yooIJSkl\::r tim o~mi.l3] !.1:f;[ects of 1m 1m 3~dllliIHl 1b~.l1eml:e 'Iowan:! I.ow·er cn,crgill-s.,\vihelil, wel Iwid[h, of 6.5 Imil, 31" 30'mK. TIm. ehslIg.c ome of ID]a~ !bUJlt :l:alli:!U. .hwel Cf~SL'!S the :Imlgllctk:~.cld, II.wo S1rni~.S of LaI;ldall!llevels im C31urn1Gi' !type: .~ dii'ootly ro:WlL'iiCt~il~t :Ii ;\ligl~ aJttil· obtailled fi'(IIt:i ~1IiI~i!lfPC'f m1d low~.2: x l: Fent'il It;;..el, them l'l'iiiui.1L1:! 3J ~il~£k;~m.gt:: ~1'.\U:t; block~ or Illiiliil .Hi}!11ntol'liiil~"Eq. ~, in\ijJi~ioCh D!fi '~h~dgei.@Il:di OQ~ ob~ins a!1l~I: QH e:1~l cli~!1Ig~ of ~!1.e!ii~ope·Qf IE[~~HaU~~5taiiC:eR~" ,.\iid] either-Oa;l' .~. {fig,. 1£) ·ot w'ith G;.y ~ il!~d\iilecalr! ditrr.'t:t!iy iwr~!U' (bat ~!e carri,~ density the twole\'el:s ,c~osc8jl to thCiFe!1~ief'ietg}' v:alI!j,ecSWrro,ri,l alileledron de~,il)'r~ ~ :~.2 x ] O~I .~ given by E.!- - C + i\JJ- ,~ + .ff;l.:, -lanclilL ;". ,-ilh {FIg. 2F).Wlien ~h,e !ll~gf!e~ic field is 2 j,I'bCrefised funher, du~ ,seoondhulk .Lruadalll C1Im- 8t ~te\lo.~l:age~~'" -to V Ito 8. bole; deft"i~y C - M- {D - 11)l~ with. l~ ~ ,j.ft/(e!1.l).' -2, p' c·to xll]cm ~I-] in Vl;; =. -2,0 V. At modest level Gmses ~itl('l Fc;n:nl:~~c.ve~, (lI:n.c reaebes and Thas, Ilrlle CJond,~ri,o.iD,I'Qjj':l~."C'leii'OiSSjil:l& is,givm -~ :~n~ginctic It'k~Ms~Ioit bol~~ l1;.1Jy~!lJld. j:l.'~)fpr: 'by .~. -E_ =2M- 2:B.I,~ =' I) o;'.l!f" ~ VlJ\il)f(.elJ}. the: cOmVmlltLonill i1[llmllllltor C~G (Fig. 2C) blllt ~ 'G~n~ran:y, d~~ B ~:;l!l'lurn!lt~lti~ <l~.w.. y:s 1[l1~~ \ViIHth~cnl{iir$ofnh¢ Landau ~~vl1;1 ~n~h;ll~. .• cl.liUl!iflL'lis,R.'i!' I,;.(I(llIibuL<ll ,!itI;l<1l'lEUlin H".,iI plm;~~~. (lU'AJ M:~'!,I~' iili!e~lbro;, ~'c:an ~e I!!i!a!n lhe ~e\'el eroS-I)· In moo~lswiil1l b!!!lk ;rb'V',~iom ru;y~TI!rI.~try if!diL~~\~ (l!rdl.~ S.ood qu.:d~tJ {Df 1lli1~!Mteri!!I,. (/1), !he I,e\i"u] coos,s,j1ng betwee!~ £1 <lnd filii I!!!n!iila~ fields aoove ~3 T 'dle~i:lJSl bn<bu I.evtolJ~8 in~ {I!lJCU!fS o!lIY~~l IIiIl:e i!Wl;lrleti ~ioln with M'''';:O. :Ulldi<ll!l levels ![iif' .!..can be a.voided,IlII'IG, the d~leled. No<mbl.c O'ruwl}(),nooh.av io~' is ObS\U'!lCd :for Tbe tan~l!I 1erw.:dsor 'lh~ I~Qrm,[l Cd < (;i~) p~f15e n:g;ioH.s (i:) ilImldl (i~,) in f'ii.g.. :2:8 oooom.c f ! d~,. -~..9 V ~ VI; :::;.-] •.4 V (sc~Lhc gre,l.ull~m:ll ~u: and. '[IM;: :i,lweli'll£,d, (,d :> tl~) r~gi.I:W.1.'l BJ~: shown cm:tliu'lcted. G ~mem~l~,ililcmO:lilm(flllfit(uaic lret! lrm:m,~i:n. Fig. ]), wlmro lim: ~Hlmph~is :iI~~ in .. fig,..2, A and. B, ~!lpec'~:ivc~,. EclJge !l;,i:affiS pmtt!MiI'lCll:oUhe l.a;f1d!l.l!l.le\,(l~ ooergies Ill:m'l IIQ suilatill~g1i!! ~R) .!i~agn~f~(: ~:~Ml(i. e., jl'!clF~F~l~ in d'lCi p~:S~'liei@ ,of a:!i ~",~~[1l0i~ ~'iIiI<lWii(:;tfc fi~ld tlte tmll.ili'lio!lllf,om U~~ insl!l,a~i:'Ia1: sl:atcll) th~ ron be e$.ilygb~:ail'!edl ~;y SOhf~f!g01l!!!' si1ln~)l~ QH sl4lte .H ,I 'OO!u.5lal~tiFcrlll'l energy,whe!l tim level is ill! the ,~p ),FOf d~eslll~1I!~itlivoll<l!~~, mliil.~IT!edcfle~d .i;s VM~:e!d, D[;.u;;lloodeli!~Eq" ] wilh open ool!ludrn),oonwe obselil,1'(l ~h'll ~he SOlnr~~~IJe '!!!nooll'oos ·01. 'phase l~nlliSlliQllilim~'W, an tnSllJ:laL;~g Shill.::~O~ Of!: .sl:a~e d1miol] ak!:llI.gollie di:~lion: ollila: pcn,ooie boolld· OlhCii d:irn'cCli,OOl. F'iglJre wi.~ a, q;IlI:i1:nni2ool Han ollllldmialloo off G'1" 15 Will, <llrY olllldljmioualo.mgiltc: ehher ft.;. Qlrp-lyP'l d~lildLlllg om i!~.211~a S:1t'ilan~. 2C s1ilow's dm Indlk and eclg{l Sl3lll!O ~hr $1 coo( ...~ to 2: T)appi~edl. m'.'lgrtlL'ltic fI('lM. "Om: samventiol!la~ ili.:'ii!I~al:oc~Wlthincooasing Ifihicklillli::SS ii, ~Ie Jremai!1J~i.!~Iffil:~QH sM:t~for.1IfCcwnlo.e T, Hac: t~'(I!' ~ro1J d~~l 001'lheFentlli e:!t~'W' ~fl· p~Jilat!!1d 'ilWfI! oro\~ leacJl Olhiiif. ''ifhis''oond <lJ~d~llilel1 beeomes O!1l©C 1!Igiliini!~,sl!li<Jli!]g." We i!:l\rers.ion·· k'l!ldi!'> [Q U'le bulk and. cdge S~.ttes (]I:~servcdl Inl~is p:ll'CllomenO!1~1I'l <l rlllll'l~be~rof srunp:~I.':S, ~~leinv~rlcd. r:egitn&, wUlh. 6.511l1l1< ,(Fig. 2DT).. n,e Femll CllCilr,gy crosses a 1P1['jJ~~of in d <; t211m. ooblntcfp;rro,p'agc"lfilllg oogc: S'~:atw> on 'l':8d~.edge, rom:~~llg m. no. fl'ct :H<I!U e:fft:Ct Th(';s~ ClQUIifIfl~· 1Ih~' pI'~(1; Inrillls:ltiol'l fromll~m. insU:lattnl,g pt'op,<tgM'ulfIg ooge $~;(aW; ;'1I1~ s;jmUm:.r to 'Im!~ 8lilll;: Itofll QiFI81:Me l~ i3J IUilOI'tiI:rivi]ijIOOll~q~~rnc¢ helical ed,gc 8ti;l:1~ofl]l,e QSH ~!1c'<;{JI.u:gr" rHo",.~· (iI,f 1!11a~ .im1ver:~cd lll""mclisl.l1J!cll!!re of the Q.g.H ill~ lever; owing ocn,~~leplI'e.5C!lCe 0 r the :n1<lgucljc su.hu:o.r <IDd can be c;:tphrlned b)' a!,e level ~le]dit_lld lID!,ehreolkiIDlg of 1!~It~ U!llle"re\llersail c;!Ussb~g {If tile E'I m~d iilll bl!lcli!lu, levels.

i~ carrier tYP'e can 1,i)e ulQ!1it·m'edi Ifoon~ Han~

~ietd-i!!id~lil;ld l~hOMi~~.!!IMitiO:"I, 'rhg d]~-'!;g,~ wtlich

;/J~

IFig_ 1. W Han resi~tar!~. ,R~ of a (J.. x IW) = 1~~600' 20Q)p:rliif OW s1:ructUll'~ 'Wi;~h x 16.Sc"'{jllm w~'U ~~th fO!' ,d\lffi~fI,t '~ml\!r('Ol~" (Eilllh'itioos '!Jbtahu!!lfo.~ 9'* vott.ag)@S Vgl of -Hl V Wttld;). -]J. V (p.mpLei),...;L2 V '_lli)_· -1.3 '(blu~ll ~L3S V (iciJgJil), -1.4 l(grlEel!B),-lJ' V (red), -1.:13 V (Oiil!i!lllg,e)I,~: "':1. 9. 'V (brtIWrol• ,rnd -2.0 V ~lilll1dl!:;, lGwer

n
2(1 -

110

oorv@ .. For ~SWlg

'V!}'

·the, 11I~,t'liPe ilmer C

Figl. l. B!!!'~kand edlg,e'5.Uilttl 5p~t:l'ljm orth'i'l Dirac rirlDd:~l d'e5cnbetil by IEqI. lilt! the pr~eme' of allil e::dE!!mal erbital IlIIflglne1i[ftiif3'I.dL (A) lh ~ bulk Lg!i!d1~!!!1 le'lffllsi!'lltl1~ !ilo(~!I'I'Ii1Ill reyime. (B)lIihE! b!JIl~ laindilll!llievetsi ilfl the i1lil1ler100 regime. A pair !Ow ~o!il!·lyinlQ LA3lnidau
fOl!Poo'lIidi

OOIliOO!ilt1a:tlOO~f~,mdalr@f!diofi W I,ll I~·tylpe ailild:m1oriis omerrveill.. tpas8.iln'g Iuol.!lgh. ,Q1f1il'l:5!l!Jlatill{l1 ~gim~ Ib~M!'),~ -1.4) and ~1.9 \fMB"", 0 T. 'I'hiliim@t ~IhOlj\llii 11: !i~hemii!tk I\\lIl~p~e llay"ootWillh (lhmk loontaru I~a'b~w~l ttl 6. lIh~ grg,y :shad~ l~eg$(l11Iillld]caitesi~lile top gare el.ec1rlOrl>eilliid ,defin:e'!l, the: p.cJ1t of the> ~.. m~ lliftere '!he ~arrleli «I!i!C.'el1ltratioln m tallid type caine!' crnnged. Rt!dI .i\'illld bll:i;e~ '..... dlrro'WS1Ii1dlica:M,lhe c:,ollmlErprrop.a,!!Iatin:g 1~1-20 ~pir:!i",claJri~dll'i!dg,~ (h~!iln:., 01~ thi'l 'OSH @if'f@ct (8) IDe lLa~H:lallli:;leJi~1falfl (h'art o,f ill !5.5.;u)m IQW o;Stli'lleaWrom al'l eig!iIt·b1lind Ik·· pi cal~o~la!ti(IIi1" ~l'ac_k da.shoo I~in;esifldi~
ICM.ethe

ler~b OI'O$Sat il.rili!ite magrne:lic ~ie:kI~ J.' Ue (;r'tJ1SsinQ dtvh;l:~s the phQ'SE! diagr,1.Im of ~t!:
ljjIoltta.g~'dllil.d magllllei{

~~~~~~--~~~~~~~

~if ,of ,mul1wp.li(lpag i1rt1 ~gJ ~d !Je~~t.rt~'S,WI~!Em the milJQWU!ili1il::fU@,ldl f!s~IiI[rea:s@·gi,f!Elltli\iollcw@Sit'"

lying tliml~R. JU!IIUI le'!{el!'i .tIp,lJ,miildh earn o~helrr;. Lj! an~ dt~y eros'S the F~,I'il!IiII! l'lin~!i9.¥ill .gl d~liif~r,~nt orderr, de;~eifldiIllQ 011 th!E! vatlll.1!!< ,of the gaIte '!Iolttaig~·.1Ih~ J[fO~s!l1g oftlhe ffirmlie;IIl'fflglybV

Iiel!d ililm fulur Il1egffirnle'£, I~~w-lyiflg1~l.dlk ~!liId e'!lg/81 $latie 'i!nE!rgiles. a~ tal fUI'lt:1itotl of the 'oont@rs of the Ilan al1.umbbls 'i 111 ~M liIorl~ill R!'gr·lllUl... (D) Th ~ ~(IViI"lyinlg lb~lk ,Qiilld ~dgil! SMt~~!1ll!r'9~les a~ aJ (!.!!Inmon ,of the C.ellflte:ws of the' L.alndau urtbit .. I~5 for the' ililiv·e;rreel mgime,. wllilem~ the If,ermi ,en:e'!lIY li'e,s in-boetweeli!l '~he: two' b~lk ilnVE!lrrite'a Laliii:da,ii' lewl:S. nlE! fermi ,e:l1IlH'gy [Nl"l!'lEl!:stfil El! L.mdaul I!E!!1Iell!s;, givUl1g Ii'~~e :kI 'Iii! e

~:~Ii'ld !~i)'tg.

~III~,~C) ]h~

e<nergill, If!'., for Vg ~ ·~l.!~lllndl~.(D,\( .. Red .B/T ~und Igreen da!:ihed ~1I11e'~ ,oorre~~Qilild'~ 'Ute IPOiSi1iicll1 of the IFemli'ill~,enNgies 'o~ the' rd' i!ll1d gre:E!i11H!ilIlI res:ilstarJii:e tJ]i!(I!!S 'Ilf I(A). The: Ltmdillu~lml, l~o]iIllBa~e welllrn~ed rily ann'oW of HIe !KImEl! miar:.

ImiM~iiJ~ positiolll o,fme Fermi

ao.SlSiillQ

.one of'the Landi;IJu levels: ,~i'lle:s rise t~ eiitliller'the n- Or thep-lYPt! IQIHE for ~nec;liws :~ilo'Wli'iii'i1 (£II iH'~ (fl'.

RESEARCH ARTICLES
Ald.~Q,!.!g~~:~~ rQ"~f-001],4 ~.rnc: rnOOl;~(~., ~) gives <l: slll'nple q~~H~;a.dv~ !I!!1Idc~rs~ndi!~of i~iIlIis novel fbasc tnmsiti.aH,we alsoperlD.nlJlcKl: lJI1C!fe re;alisti,c allld s,e~f .cmlsis:toml ~.!1Il~bMld ,k.p l:ti'I4lId!el. calcllI!liatimlS {.13) for 816,5~nuUl qUlmni" l~iI!.iI1~. , ... d~,.wutllil. t~~~fl1JI'ielila:F1l (l!r 'l.h.eiLam1(ibu
~W't~ ~(l d~c~~~ t~ !~~ity;d~ 'fM~ ~~be.Qat!Slcfw ~,esc w'eU 'WidtUl!l', the b~)dg!!p ~Q

IQllgerooiOli.l:rs between the EI and IlH~. kw~

bUI

'els,

ra1'hflli

~tw(,~]1

f1l!~and flln-mlm

!;e,CQlm.d OCmfii~()d IKI~.c:·Dik)e[Clv~l, as SlD~hema!lieaMy (;iho\'\i'l~ in th~ il,~!l1~~f Fi;@,• .3 [s~~ .tli.~~ o !¢\'~~s:, displa)'$dIimFig. In. n,~ tWO~U101'tl(lj(11)]. Abi:o 11'1 lli:$ re,g~lfIl~ b:iimd ~[~~ing ·of ~ •.a ~g!:!sL~cl!;'iu le'vets Cro5sa~ a crili)~ ~~~e~ic w~d1~Cl:at!Jl00- {liBn :~d \'.i~e!'!.oe- (HH2) b;:Uldi~(!u~tu!i"es we inves!lg<lloo. RD~~ is !'!lost.!red deriv,ed .l.1!'Ki,0\11.I levels OOCUiUS with fnc!:eOising w:bHe llie:Fe!1ltl ~eve:1 in the de,vtce .[s sc<u~!ied. fieid 'if~ \%111 11 evid~!li~'~Y c dCpe!]ds Q!~ weH wklil'!u. lltil>h~lp~ies 'd11U w',hen a ~11~,le ~~rusims n1a!1,Il(lil'ie ficMI (J 3, 1 i;. 1~1. ,Figure .3 c;1.c."ir..ly I!~ra~b l]aegap. li!fllhe law..l:'CSisli1l11oo ~g-[QIlS at F'crffii:~ 'f:ifI~)' in ilIe g!llfm .rom m~iI'Ie:~ie iU~trilll~CS I~llil~quantum :pho;sc: Itrnn!itioilli 1111I!I~ posilli.VI(i VI;! .~. V~~ Ilt\lC :sl!ltlllli~~ is l'I'-tyjl'C~ lit oeCUil'S IIS!lr(lil'Ieti(i~m. of ,til in the:: .HgTc:: QW,s: il~h,IC V8- V!I!!' the safl:lpl,c~~ p~t,y-Plt fi'ekl. ihis ,eme:rgy wHlllllw8:yS be croMoo by Th~ b~a.ck C!llf'\!\~ 1l"iJ~l(ld[ i.n fi~" 4WOlS I~~(; ~wo :;ll,!an~alo~lal~&M1~~V~~(\1j~~llil~~,.l~ OmlyfOird i :> t~~ do~~ .iff' J. (fXiS'l,,<lBld iU Iljfil~ ,ar!1edim11-iSi~ [(20.0:w:: B.3) aQH p.hM'~"ul! i"'-b~!'Weell[he 1\7i,.fO~.M~S: sam~ t!in'!e tile: '~¥!Gf!W iG~P Lis Il~<!tiw (i.e.., obt<i!i~oo &Oi!l!1 fLe~,&. F~8J!l!lre 3 sUr1l!nru:i7.es: ~l~e depe:~d:C'~ce U~eband S!I!'!I.!C~~lle .!lsiW1.\re!'b~d)~lhe experim.en",!ill] device with a 5"S'mll (iW ru~d sl~O'wsthe vlor of 11'..l.O'nwell widlh d. The open re<il,8qjUlOl!'eS m~ da!l'IiIl~o~1!! for aq!uile <!Joca.nml!e dli3!1.\er!M~" bcl1<1 we o·ooerv:c (or !In de\!' ice.swi~ih <I, nOnlr18.1 loanGli .struGLUrc,:~ml,(Nl ~1Il(il crm:~ :~c:!Vcl F are c:xp(l'Iill1lcllital dasa 'poimns Itlil~t re:mllifrom nation of tbe:: ,criliellD 'thickness., ,ieldin:g d"" ... 6.3 :It 0.1 am, fitlitllg tiM::: ,e~~bl-b3nd k'p model 10 CXPC[I~ is in d~c:g;ap" R!4.~' i1l'lCrMSes s:lronglyalndi is :nnoo'n~l&la. asill'l. Fig, 1, white: [he' filled rc<i! Z'!!!Iio4ii!!!![1lI e,dge ,c[h a nll1l~li:allld tlke Q5!H !I!II~l rovj;;''H'I~ teas of rliLegoh.11l1 (!Iili~Sis: ilm dierocl:ioJ'! l;a;il~t(ir I.hilil!oCk~n ~q;i!.!Jpn~ritu.~ in tnll'~!1J,GlI~ 111~~i,~!t oolilal~ f!(ll't! !lh..::l!i:·p, (:<'1101;1.1",- ,eil;1·a::t'fI1¢lIclpl ,exi:S~~l'Ice ()d~gdh,anm~ls ' (If 1!1C ~~Xlrimc!~l. lJrhis cleMy .~~ U~C e."!POOledi t!:i<m. f·Q:v !1ii.lref~lcc. ~lhecalcll!~a!!oo!1lap '~n'ew- ini,"~l!!bUhliS, ul\i'~flted QWs i:so!flly [!'e;w01!led oo!Ulvenliolll,~1 iUSlII<lID!r. Howgies are'<l!~80 pial:liOO in '1l1is ~!.l!pb ss Qpel~ when .sU.!dYil'l~smOlIk!: Ha~~ ~\]!'l'l rU~c ~;ypiCilli bch~yiorfClrOil blue ci.roh':~."nl,e 'band inv,~siilo.1ilisrefl;oob!~. Ilrmbil.~ty of 10.. en; "irl !i-I i1111il'~YPCm~tc,ri a& cvc:=r, fur aU devioesclQlll)l1{liIi,IJ~,a!n. ~nvel1ied QW, im lithe si.mtJl Ch81~gC' o:f the} gap'. F'orrclll.'~ vely irwj?;li,e;,:;IUiI elastic I:l'aC,m :f£,oo Pfl~", or l!"'l"p :;:: the res~rulCe In tI~:ifllstlI3timg rc,gjnrut:: mmlllimis w'M£wc~,1,5 (d :> 8..5 !rum). Illhc (in'!I!Uli1.edl)ga.p ~I!lIliU (.19. 10)---..,a1ll0i {m.'L:: m:iliy anl.i.cipa;~.e low~r rinitel. R.• ,~~ l!!!~aJ~MI1SIII weB ltIekJ.-w HID kilol:m1 4 (1.1;.\" .c; ~4.23 = 0.3 .e"{/l) :~hr I!h~ blu.eOlLlN'e l!lbck;d [I, wl)id:~ is :agaiWl. [ijf a {2110 x 1.3,]) .!!I!f!l de-vic~ (aOClCi.!too- by op.t!~1 li~og,r.l[ll~y. IF'lg.3:. Cfl@:iilflg 'fie~ b!Jllh~t cOO1I:<l!iu<I 7.3,.nil1=wide Q\V" :FOf n111!ci! SC.,l. (r,m 1inalfiglel),. ililild S:lmrtl.i1li sru:w,~.cEi {l, .,. 1.0 IJ:ltl,.~~1il and red i9'nErgygap, _J::~ (b'tIlEl ClIINC.'l; 111 and ]V) fnlhrkatcdfmil1l the smUG open ,d\)tsl as iii ,rue" \V.arer,. GI4,!Ji 8al~lmUy roaches; Ihe rffid.iClM non O'f QW wilidtlil' ,€I o 1t1lll' va~u('l close to ZrirlJ. d~mOI~radl;J,g E~~~e~l{l~-' trre.wffitingf[om i!lf1I,el!ght~ 1IDO 'II' I~a!f!d k· p' ,calb:tI!ItaOO!l~ E: ~[! renee ,of lIne QSH~!ls ~~ lOt ::;;;W¢ Ii::n iiuw¢rI~ .. -, I ffiir we:U mldths III r'ger H:s:'fe 'Qw SlmCWtfeS. , tlilarrl 6,,:3 mill, tille' QW l!i Hgu.rc 4im::ll!I_des: dat1!i 01] two devices\!\,r;~~t i~l,II~ gf1:d ili. rid"ggp d "" 7.3 IlIn, L "" I -")!MIn. 1l1cgreoo. 'Irac!(l (I]:~) l(fll~ttgof IlliIrndau.lew~ is from .~ dib'Viccw.il.h. W == Ul jJlfiil,aoo. ihe rOO. deli\tllingt fQ'llm 'the HIll trace (IV) CO."I'ID'CS]XIOOS I~O a <ilE\.t\i.o~wil.h. U' = (!m(:l~cta~'~~nd Ellta· g 0•. J,uJ;j~ Crearl)';. i!l~,~ 5 ~sidl!l'al r~i.(l,lallc~ .O\f tit.; It!!ll:OO< bimuoUlilr:s. tilt fiii.. de\~ces dll!~ .!!Iom dep(lHd olmU]ewidd~or the tillite,ma:gnEtil Jiel~~. he T
"._

!1to~l1i~il~ iQth.e!~.Q~ijf.!;:iUy i.!l5t!!J!!t~ngregiH'!~1 • "fhe pcr~I~I~ data .~ s'hQWI] ·imJ. fig. 4,Viihicll pl'ots, Ilih.e z~'O .8-"f;icJld fmlll'"lcflilil1i nal resistance J?~4)j ~ Pi!5/1!4M 8 :~il1llC!~ionoJ 11On1m8!1i!md,gate voirngc {P;I", is defined.1l.\l ~Cll \ld,~nR!g(il for w~~id~. d,lt§ oosi;Gfia1flce is liMlMO !brg~';I~~~VL~ II.I~ilt a~[i~(~~ll1ta!liv~ Qf 'I:ile large;l1J;iiflloot or

~pt:!Tu!e;nta'~y OOsfrmi tm5~,llilgl polntlillNlindicart!ed by Ol~en red

sq!!i!!J~ The' 'iIilS'~ s.h~5, ~liIe leflNgErtiC ionfelful\ll ofjjJe IQW wbband !itr1!l(jme

tIS,

ill 'flnllrnOli! of qWwidt~

d: [S:ee ill~o, Un).

~lle ~r.U1iSpo,n OOOM rs IUh.roltgh eCl@cchambc~s: (21 )., T,ia;c ~mocs liG, ~iIlI~d"'"7,~ mJilJ, .~.., 1.0 ~lln devic~ do Itot [cae.tn.all dIe: w.8iyint~ the p-r.cgion beN'l.UIl$ethe ~lecIrP:tl-fueaJlIJ:~i'l.lmgmp:hYledt1:d t,p ralOOi.c~ th~ devfo~im:m~e8 the i:!!It!~hl.~ic = (I V) {Vg
S:!fl!l,cU;!!rC. dUll

VI,lddll~d:lca]cs

varioos l1'1')f1:1lai~ (d'"" 55 nm~ 'm·alildil¥elited (d::; 7.3 nm~

IFig. 4. l1h! lDlig~lkH.!tr~ tmTiJiMt re.si..taIllCie.Il'1M~.' '00

cOll:!?ie:r QQm;c!~Ali:o:n. WII,lddli~.[Q!%,fJl!i.!c(uarli:o;!!S I Oli! ~~e 'conduJcI:il!,uce,.~Ii!ite~u ~tace-s,.IJj,~~t 1n and IV are :rqlrodL]cibllc and d,o not sl:enl frm1~.

21

1l?

j.-~A:.o.-II\-_,jl

1~~lIifli!J~'~ s:amed~,ce $i~ OIl)M: 3ifjl ,tiIli!K (gr'!elli') !lInd!

~.al1l1Jlles fJCIIlI the sam.if!:wtlfer,.

.~~ g~ d~ '!he ai~ Iiii~r,ed lei' B .~ 01 T at r = 30 Il!IltThe dE!1liiLe'sizas .;lIfe (20.(D1 x '13.3~1 j,lm2:klili d~~ IlIlild[[II. (H) x 1.0) jJm~ri!l"dellrii\iie IU.<lU1C[ ... U If]IX t(JI!.'SJ 1J1'If1~ d~o~ IV. 1Ih~ l!liset .shows R:ful,23.~lIgll ,of two,

O~ !I'll,. <IInti M OW :5I:rmres

~ gfu~oo

e.g., eilecl:i':tcalmoiS{;. A~illoUigball ..R'I4.,23 1~!I'aOes file '¥erG talkeo. at the ba$': telllpero;~l.I!ru (:3()' .1.b1IK.)i o!.IFdJi~lIIli()n. :!'¢frigcr{!I~l
d~SClISOOd:SO<

rnJ

'Mack) m.kI.m a.'IUI Kiroon :Ml.other (U) )([.0.) lPil~:l~amp]c:~'whj,~h, Will< I'"aibrieru:ed frnnl th~ sa"ll.l~wafur; .Imt thefa,'bric:atig~ ofl!lis sa:!'!'!p..le, we~d .. In,'Wet-i~h!!!~i!iaU.QrI crose ill thee-be<iIn l:i!.'l~oS:~~jl, 1!e!!.ulI~ing lJn. a OOU:Cf (but s~in 1)!)ilq1lliwc(HI.lplele) covcr~ of
II. U'lMXl (ill

;'i~Q!",h~ 'OO!i!4I1J.!ci_<lOce1J~.1!:~~lI!.!!~<!re!Plot ~~m!ted l tI~ls 'i'\.'rY~lQ''!!l.'..:~egn:p~l(!~ few,me, I!~ the j,ns:et ofF'ig, 4,\1i,fc repf'Oid:u.ceiJiI'eg~l~ )O~m'K traCQ: ~n 0'111n lincl1Il:' 5C1iLI.e ,~ut;;l ooll~lpareh w~rili,
~Q

(L 'i>: ~,=

1.8 KMad!:) ootll~~eaJr .!iCa~.

the

1:1.;.i~p' tmll'ls;irkif:l. Clearly,

ifni ~is

.fd:rther

s;:1iii'I.lpl~).a.il"Id at Ul K~ I~~~ 2e~/tj 'Mf~.du.emmre

RESEARCH ARTICLES
pI!Q,()~i¢.~ m ~~~~~g~!t)e wid] i!lll~t Qr fhe ~~ng~y\":h~~th'lli ~l1eijc iP'!leSel14~n~!Jdh11l. O~~~.!"~n1UUy 11~e~:~ '~~5 tki~d is ~i!Wd. 11m\! Ute QW p~!W. !PO!' fu!!y Inc- reQen~y dis!l;lQvercdrp:"i:i!11e!H~. [Ill !~.mY' Wl!y5:, ~n rili,Q .p:tJII'C lwo~crnj!lla~ geometry, w~ilh. plan.e r.,dd~.lhe: QBH OOlildllo!_ce, can be 00, the H.gT~ QW sys:leliu (:;l1In be \!f~wtd :I1IS a scrved OIYrn"SI mucln,widl~r Iliaguaenic fiCildrangc (i!lllly source alDal dmiill eonraets (COrlmc1S laad tllmlSlble gmpbCll~ sys:trnu, wln.ere the Dirac O 1n£l.!iiS term eM be ~1Illfitedcon:tnll·IlI.QUsJ.yto :zero 4,il,1SCI Oir .rn:lg. tAl. lbl~.e ll.wo COII!II~m·rpfOp.ag.3t~ (Btl.i!l!lM ::::; ."} T), niL'! m'u-~'i~ o:W[h~ h~lie3l~8¢ iln~ ill fr'O:l.i~. ~ith~r the lP{l,si6ve (to~ol.ogieiilly img h¢licld ¢.d£L'i ~lal[I.'l~:.ilIl.olfL~ ~~I~ i)~~e 'OOi:lJtrij.v:~~J) r~he ,~e.WiJ~iv~(toptl:IQg~c~ll:y!lIonQ ,~;;~red by the Hitn~"'reve!1'i~l~l~tt~~ A !Ti!~~~.[ ~'1'~eh@ini~1 porenlia! from (he OOu!'oo i.wd dnd!i!,re8pec~vel)';.('illd !!hley <100 ImCl1 hi netie field b~b l~'~!lle·:~~<li! !'iy:Qu~euy and triv~al)' side. Ut~8 ~1!!!mSn a gap ~etw~e!l [he t\~lo()!11e.rwise o Clq'l:.!i~~bl'iu~nwlilffii lea_Cla ,otl~ei be£a11!Se I!le: e~~:t-c bac~~limn!ll'valliishes: betw(lCl~ihese tW.o chmhr d.c,gclDer:ailri Ilclical. ,edg'e !>late!li .. llle perpend ie" R~M~liiili)~S,Mid INcJtes !Il!c:t~.In,lbl~(ll1lbsel;\OO o,.fvoHBge p.ooks .2,.3, :5. Silld: uler 81~d illlP.!:lI'UIC I~il.gmetref:ield l~d to d:i~ a, S;.i'I"lriil<:om~ N. N.ag,aoi.il' s, c, lilaaltiJ, ScJ~(if 310tl., 6 ss iIftlcl:LcaI~OOn. dll~~Mic;t o,f .fl.g.. LA, the t~'iIC!<- f~iU gaps, d~Cli1dlng Gn. d~tlllfll.'\trb: cl!~une:nlS of i la4a(zowt 2. J.:Sri l!!Ilo'!'oiI ef ~ .• llllj:l. l'l'e:v:.. ~tf.90i!. lJ:66o.~ ~lOOt4iI. th~lll~!pilQ-t~zaliojfJ a~ra;~~r.:.Eiiil\[1lL= (11'1(;1] .• :~ X 1~~l'IInin~1ool~di!Ja!:ano~ ~1~ouldB:u"'~2elllJ.]!'l tl~ 3. S;.M~~<!~~~ N. N<lg~!:)j;jl,S. c.. ~II;!~~ P/!.r:;; Rev. tell• f:~~noo of n~ voUage ;p"ob~, Il!Ii1e ·YOr~~ . + :J.~;!:l'S.tJt~)lB1Olnd.E!j~JlII = (1i~a~.eJiI~~~!.8]J, ~ ~tl !)II;,!, IS68Q4 t2:0041 IfileaSl!!rc'J1lCn{ ~ooessarily .~~ to ~lIiIe Qq,uilibra~ w~lio1~ i,~are I~!bepoo;iticm~tld c~ootrie CW'lref:~~ ,t. c, L. IKane, E" J" ~lE!. ill,""': l.ett 9S, UOOIiI2 IHem of IVie two 'h:clica!l c:!l!L1nDlle~ w~I'h Intu~~pOS[oo l oper~Drn:~ respocti'l!ely;. !!!Ildi i is 'Ihe ~mit"'\!'ec:mr (2'OO~_ $. 9, A. e·~rnlf!'lli~l ('.~llIafll!l\ iPJl'~ ifl!!l.t. M.t 96 .• 10111902: S, spillfl oIiilCil,~a~:iI(m.be<:mllise ~n(! volta:g.e [probes are perpelldict:llac' to. flnc,QW 1i',lrnH:: S~n} stan& fur .. ~200~. lilI.O! spin :S~flslti",c.A sinlll:.p~.e Lru.\dml~,~B~lIUi.kGi dle d:LO!l1JetttSi.Of~liCSS :pai1 of the ZOOlllJlMl1.QOlIp1in1ll 6•. 8.. A BBrnl!\~~, T. t HlI!!fue~. s. ,C:.ZlililiIlgl .!\(ie..l"-i' :3::1.4. 1~:!I'peof eal.ctilal:ion shQwg l:h!lllltcfOuf4G.l1uimlll matrix dm:nm~t in.l!lpci'p('lilldiiclJllar (psra.nG~) :H57 (20otll. ~i~~ce $hQ~kl ~;~ &i\~!] b)' RI4cill = h!1iz. [~I~ Ul~gJl~i(!: neld!. W~ .~. ~~m~ 111(:; m~[j~lu'de 7, C:,W,<!I, e, Ill, e'!:m.,;:tri.g,~. ~. Z!~~I~ flhp;. Pel': klr.96, llMiilOll W)06k 1~ID!e ~reIiern()e u f l.'Ile vol~~e probes, I~e vo~~.a~ o:r~~~etwo;.a~sby !~O~~S Uw <fj7.:'!i" a, C. XLI.; 1- Mornr,!!',f:J!I'ys. Ji',Ev_ B 13, ~,~:;I2 it 1[~!lI6t dfOf}s Vl.2, !If;!;., :<lnd. V.M <!.d'dill !!iooeslo !!live a .r!'~ and UI5'IfrJ-lil > .... ] ,hI wbich l' .ut\! ~ Inc· ~he 9'. it s. ND\\O!iIiiliJ)\1 eel at, MtitjltiJ. 43S;. 1_9'] (101lI~. fell111~. VCI.OC.iI]Y Sind! wkll!lli of tile edge chilllnelli>, bi~cr l~islalll00 orf R','i ;;;; VI"!I'; - 31t1U. Iil 'I .. Lfr~nq.'f. ·Tan. H. t. SUII111Ill. P. IKim, MJi.J1[(! 'Ii~:lt .2O:I Gpooli vC'ly.. "-". nd ~ call beob'l:Iliimoo ~rorw. the a Th~ li'CSulJtsare v31~d 3S.~(mg asll~c d1.SlaillOO (2005). bL'5tX"'~~[1tim '!IollBge:pro:beg .isl~ 1~ltIam. tiro Diuacpara1ll1ctars as V= ilH~81J.d~ ~ .l~W'IA11.TIlm H ... :'L I)iiij, 1'. t HIli$lIe~,. X.·1l. Qrl :Z. ~1I1lg, :5.,(. 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EHT

RESEARCH ARTICLES

IMlollecular Basi:s, f:IQ1r 'the Ne!rv,e' Depsl1Iden.ce 0" Liilmb IRs'glsnolr,at:iion in aID Adult Vertebr',ale

nillOl_ndelS earn. OO:gNW _ !Iii'! n:~npU'!<I!le~~~mb. '.J]'li sreg.CUlcrntlj:m oo:ctm> GUlly iflhcr,cis siitlu18me'()fll!llru~el~ (l:fl:J!ni01fl of dlL'l s(We:rotlln(l~('S+ Aid~o,ugl'i \V('l 'lL~[~yl.1ilffi'ikof l!mJL;! 1:l.~I¥(l!!.!!L~ m~ <1S ~ ~try.ijn,g
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tbiorcc.ioximl .am.d.is seereted fnnn. clll~ls~ Willlil IfiOO il~lp arntiOOtJ't(!S: ·of r$'tcti~ 00 '[\,,10 .~gi(:!rb.<: fnt\,O, o

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wilhil'l!gfu.nd cdillillil. 111IiI@ spc,. ci;l!liz(!)di \l;'ol!,ll'lld 'Ll.Ii&l'J1I!:i~ at ~~Ie t::i~d! ·of ~tl~limb (C,).Th~s epidll3[IM~is cr:imiml fa:' S'!:.Islrull~ .l!attr. cell pro~ifl!m!i01Il.njhe i blasl:cma. DIe appe.arnlll.ce of ~:e:nti!Jati!;)n ,of' sa~IiIiI~litd€r iimb$ reqlJ1:~~on(oll1itant l~egeneratiOlii 'l'lf: 'the: ~ve ~ed nAG iml.bod~ tt]1l~SeI~Wallllll cells 1~lIiIalll1~1I'I('l reg~rnle\l';:un",e tisiliI!IlL'i,. uti the\:voucll epude;[lJni:;; is 1!1I1~ limb iSt!JIlrtlp is ptta.lUm.1;Lml~ il'llN,es,. A S!iftlgi~~ ~tctt:jn, fl!A.(S~GI!!fl S!UbS!ii_ ·~CIf the: re~Je:lileriliM gl Iile\rw' Q\lu's. amo,i!P~~ ~ &!tervMlCifil (D), iy dene;Na!iOO. ti]~ ;U;lHiis 'Clll'· slmW:[l1lg lkat e1IlPressto~ln. ~ 1~1!Q11iSd~pemdS on <li.X0!1S.]lJlisojalJ:d ceUs I~ot ~gener.llc, '<!i[lC:l~bnb ~~genemtion rOllis. clIIhredfimn .~.~ IbI]as~enl1l,InA:G I)roJllO'!eS :prolilcrflJirn,l (ll ILI\G can, be 111~ IllCl"lfC depcail'cll.Ce of H~.tIqeJ1CJi'a1:tm~ WM discovered li11l. 823 by ] fll1ifi~laU.ye.;'i:p;ressed in tire dWrl~rv:atoo, !all1mp 'by il'ljoot~U1g p!]ru;l!llid DNA Jtiml. Tweedy Jo:llm To&.!, an ElJiglJsh ~I~ystcttan, ao:ill mmIymdi in tk i.940srnld ~.9jOsby Mru:clllS S~l1gcr. Nenr{)S .fUI"e re<gl1Jur:ed IlliUJJY dilNlnmt sorts of enecdes nAG 81ld. pa.'>Siin,g 8Ilappropti~Clm\::ltnflCll'08SdlC: lUlrm, 8. prooOOlll.ro CliI!~~L\Id~t~lro,f,I<):ra.doo Il:In~(}rnilgM onUs to lake lip '~temaI DNA. (O).m Id131 rogefl!~ill!iolil Ln.bi;nl.h ¥1lirl:to'IIDrutes nd In:~bn:ll~s 01 ~[fu1l!PS oo~mlim d1ll1t a ..... WL.~y <WItil i~ ~~I~, 31~ I~e reg,eneR!l:OO ~i~l,i{; ~ht~ad~!!mm innervatioll. Sill~~' £'ih()w""6d lhilll d~lH~t d blasll'llllll 50 ·~md. IliAG to;; ~~d ill~ (IU:u~t\i\~S(lIi.ll~il'lg .~laI!l:1j~I'lUlewl.'nund ¢pi&rmi~ 3iJiC: ~~li51~ (E), ~t1Ii~f 8C11L~ny ·at ~rli~~ C(Dll!ld $~P~ re:g(:fi~ti(m 1lltd dil~url~gd~ ~{:!lldluC1iOlfl '0f Ihc UC1i"!i'C hnlJl.Qlse nor n:;.. uLraVlSll~i,tlcr Irelea..'>1;l Wa5 teq~Jiredl. '11~e IIW1dlS~g,ses! Il~t mAG I.I~I. is nJJnl""l~yrretC'ai!cd, fW.llldlie SJ;IVW3I!Il m cetls during regl::IWrMiml,indwes IUliI!l: :gIMds (~, 0, Mootslrildng, dilern1iliH.ci.al TIlle n:1:Ci~cllllarbasis, for col!:rIfnlllnimdon bet'Wc:ennel"\l'CS and, il't\gCil;lellatimlg ei!'ip~o:lJl ofllA:G :U\3l11.es Ole deilCifN'alOO, b:~kl'l1Ja so 1d"D~ ~~~Ihwb I~issm :has~en ~leaI:~ ,flt~iIlll,gh, v~ous g1(IWlh f~ors. have boonpoo.pooocl regcmmlllgs lDinJJ.!IgltI I~ilemlliru I1dssirng I?rox~ma:l..d.ista.l, ax:ils mild. fOOliiS dl,gils as 11iIiooimors:. OW'pa~r now~.d(.111:i:fi£slIIpro~eilil tIiImcrulft..~U£ tIiI,('J (O). "~.e~li~,d:ten:;ql,Jlin...~!at :fQ;f 1IIiI(;l p~l~~ o:f :'lerv~~~Il"iln ~le!{e: d~]~.Jl)!'tl:t~IilI~I~riI1a3]ild in.dl!loe ~g~l!iJem~i(NlIlfiMI~lil.lriIlb, '

cells and dleinrse;!.lOOI')!andnlo" I~Dr l.;~5. nerve!> are also c'ssenl~i!;li For tissue regerH,~,", atiea, Wh!Hl $11s~:I!,amMdtM' ~ilttb 31tr!p~cl ;,It m.y p{tK~i. is 1!~i(Ji!'I\, t'!;om n.h.~ .srnlollld{;~ ro I.'h.~ fmgc:rI:ips. the stmllp rorms.Oli blm;.tcllila" a 1ll10Ullldiof ~cn: ce:U:!i frolin\%fhichrelllC4nCIi~ ariol'l. ~gin.~.. n.,e; IrU;i1"!l'illsup,· ply c~t by the amll~tmion a~~[)r~g~uQ.~~1~8, and d~is~ .. grOf!Ji,fl!i is: !leqllli!'oo for ~~~ I;llro:LifCl.'mim]. i()\f lilac: b~1ISto:Illliil~ cells.[W tile lletVCS are OOlEII~ 1~~1C::base of Ihe Inm:b,dcc~1i

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11l(l;lin~b b!<'li]t~I]llI.~i\l~ .~. 00 ~~~lJI~ ~;~y ~.too i~ 5t~~Qif!Qngiu {d~1d bla.~.na ,atIhe~'3l gi~ d'j¢ t~,<lI. ~aJ!d!.!lOt ~~ !,Il-!~p!.'fomrsd. ne~l1::!l'! i.,,<l cells of t\Ile blllS!):I1i,l!ll can t!e be~cif1eCl aco,"m!l!w.gto~~m; sncilm:s rure being ;fO:r.lnixl~n.O"I;jmt wlaat ~n twes laMed. AIl<ilysis ·o:rd]i:>p:m~rty ledl ~o'tIle~:viQUSidtl]riilic3Ilo.n Oil"~ ~;.fl :oman rnn01ll'.in, alil.cl:rore<!,'~.o rilie swfitoo O!fb~tiI",l[J1~ cel~~ and (iNPI1il;.~ iml.l'I.grnditoot along lfihll: hmb (1iiIlilroPRXI] .~ i ~~~ fijynd ~in'ila1ly .tlWIcl at c;li$!~~ ~rnl$~P~ I .a.. ~nlbGf of :apjf()ll\lil:l ~~r.r~miliy ~l.)6, d~~li!~ ilt'¢~o~ri&lt~iiy of~. ~~~~iliJlg ~l't5~e.5. ~1lI;~~ to< ~b~@ ti~1djJ r(l!, 1\"00 1,\1i,11© (:~&l!Q~oo.<l! ~!'W.!'! i!~ To yeast ceHs iIlIKi. i'd:ntufled Ille n(ewl)jl.:Gpm.ein, Thus cillnidJ~d~te·~i.ga1ild,IlAG, i
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A. §etleth~ist. ,Inig:~t pMfe:r to see ~e ~li.IIl.Ct[OI~ fmA(l ~estcdi by ~~iMvnn,g Q the n.erveinlaoct an.(! ~n.ocl<hng oU~Dihe ;ex~l'eSl>ri!Jl~ of ~h.e Iw\;U gme indl.() riiovafll CI.l:Hs aii'l~r8ilUp1.!liatiCl:lil. Till!): l'Willlipubioo Is 1l.00l.~ble eajhe !i.a.kuJn:ru:iI(h~r !Ii p~lnt" but Ithe ~U{: ~,e~lllll:lntwe ii1L,"POl1m!ly l!told p~m~~FOT flJ~ e~orL~ tQ.pmm(ii~limb ~e.em~c;rti{]f1illL!i11~1~1.'ls (.1),
1. S. M. (a~I~I~ Plil'llCJPI:02~ oJ' ~loeI'(m':l~ 8iolD(Jy I!EIs€Yi"tr. ~Olnoom, 2COOn, 2" lIi. PiliWfI.). life :)6.., IP-60 'tS4lpiillmbtr ~bO[ll',

Slilmlltl'aI)fReti!l!iI1!fI'e~;

RESEARCH ARTICLES

FULL-LENGTH ARTICLE
The: limb blJai:SM!liI'Iall (jells of iilli .iiiluillit ~lil'lm'~lIfuileli 11\!,g.emelf,atetlie· :S1:lilIdlill1e5 dlil5t:a(·IW·f!iiH:!· liJE!:\I!il!l of amplidatiollilillltdlUlIl!' :iluniIllOO pifomilil Pliod lii5 a cl!1iti~llllliI.et,e:rlm1iIilBln~oftllf!'iir pr'oo:imodlm~;a~. illllem.itJ .. 1J"'e~ante'rl®!rglf.adhlll'lt. !p!rioteirnl f,alllmil.y n'lelmb~r !ibAClis;) ~(lre:ted Hgalfldlfar 'irod! '1 and a ,gl!:,~h 'fal,ctorifur wlltliJlf100 lII'ew~ b1aI5~Jii'lgll.l;~Us. iiiAGI 'ffi!!l, .$eQijeii'lti!"illt~ e:c!,p,j'\~$!'!:d afte:!' QlnlI]Hfrtatil!i.iilin ·th~i!f!!1e~.r~Uf!!l illl':li'V·E!: ,1!!ildlth~w(HUl!d ,epid!i'l~mi.s~itih~ ke~ 'iI:ii~~IIi!El:S:oftlt!~~t'!:m l~e!ll. lilliidile-alri.dl lit! 'i'l)1!I~f'i'l~~ig!ii Ibi)~tri ~~.:ati:Oifi:S:~:;,,i!b!ll!il~'al'kl:dl by de:!l!ll!n.I!'!UOlill. 111.1ll~o~l hi' Ie-,XIIU'lI!Si5lIDI'I IlIA.G a~1!11 e;~eal'i!!lporaiolll of is sUiftic~l!lmW' I'i!l!S(il!JtI!illde~Ii!I'\I',artied I!llas1eiITIIlil'l i3illlldl lrEigll!l!le~i!te t'lIIe di$talstll!u~rulre5. (i.lllt ill'lallysms:tllriiligstog,ed1!1l:f time p~llitj,lll'lalli:dlelllit:iy of t~e 1!l'la~eliMlil rnldlU~ dlaS,5~:till~. IlrU!IN'.edepelll!l.d'e;l1lceo:~ b r,eg,ene~JiI'tiiml'. lmm

QViNn;:l;pph~g ~M~~~ (f~g. ~!!)). ng C(l~di~ml~cl~lwt!!!!M was ~~ted w!lh l~e 1·N,Qlm :PS(dIS tmlSfecled. so as tocxp:!"CSS dre m~'iiho~. newt ~ 10Jild.te stmr[a.oo. 11mbiuding of IiA.G

m·dn~ slufllOO W:!lI> dmecred byp.1~osp~l8Jta.<;:Cilab¢1~dI .s~nW:tyaI1tibodjes (Fig, IE) mid .\%i'3!i: a~"t imi I~!'!!~:r~~~ PS ce~L<;o:rafOO"~liQIl '>\!llh wn~! 1'1i!«IiwmrJftlf!l !ngCklt;ufb~r~O[OO ,CbS 7 cdb. N'Wl'ul:eprgm{(tJu e..pi~!i.iti(}il Ir~r.e..geuemtlrJM. 'iI11Ccxpl,~:ssioll of'nAlG ~ro1.c1i11 aualY2M. by ,vas mact:ing sectl{i!m,Oif the n~l,.t lillUb w~lh Ih~ two
aHtilOOdi~.:.'Un'I~ I:h.es~ .~ve:oorr:upar,::1t;i!~~I1.~ (111[:.S~~h~ !he .!lQ:m.'!<II.~im~,U~em WOl-15 ~. st<li!rl!1.g ·of a !ruililsel: oifgllaf:!ds. h~~lIiledermis (IlS. :SlJ\~ll! a:t'ler rull~utni{m lhe diis.l.d l"l'ld.ofd~C!

h~iS;hls i!]~Ci Ihe pGi~lb.i:H'lieslb:r irt,l,et'!;:er~ a:li~~g ~ c(uupJe.x SInlClililroilll mI111!.wnu'bmlics (1) .. Rl\g~fI.ll'i'atio:n'proccc(ls[mm, [h,e li~rnb b19l'>l!(M'f;I!aJ, 3. rmnm.t1 Ofilil'»i1!;cud1Yl1tiiai .s;lm~1oo'lh: 1!1Ilia![ aci~ ;.it tll¢ ~Ulc1 (If 11!~ ~i!lli:tp'" A MOh<i'OOI'11!~ a~w!):;!I's!'el}~l~ :Slruc~ di~l~:o iL~le~~1 of (!Ilri,gLrI;!1 wrisl~]a\!~en.'I:!I ghlCS lrise 1.0 lJ~e IlJ01nd, whereas .~ simuld\;:r ~lM!!L'ilWlg~v,er;riseto the arrn (2~ n~~.blasl£lm~.ooUsare CIOlWtlilOO. I!D more:p:mad~ual,oo:Us by C'J<pmmre: lDro1!ifn.oi'C acid air 00l~, rolimlo:i:ds Gwr a liil'ilath/'L'i~Y ruarmw r:lm~ (l!f~gnc!~I~f<U~g~l (3,4). lll:~Sful!l~ing~ecd! t(l l!ltim ~d~l~ifica]L'On of Prod 1. it deronl1!iml!lII ,of fJl!lOXi!nod:L~!1! (PD}identi!,Ydm [s:expre....<;sGdI It < 1~lIileocU surface .as a..glyrosyll.lffi1osp'lmliclbtllnos(» IW~.(GPI)-mooorocl :pmrl~lrul @f the ~i{6 5r~pcr~ faulilUy Pl TiI1S ~p:ressioo. i~~~. (P ;::.D)Iil~ b['ltlll uonnal allJlregmlJ.cmt~rn!illil:l'~Jb~ (6),.md d!st~ I~Uj ofll'l!:l~~t ~a(lll bl~~lm ~ oorn~ ~e!i!ed 111 !MOre p!'O!!L.in'll~ .. (iC~1!ii fO~~~Jl8 f~ e41e(ll~[Q!~ (lira pl~1id lex~.g PJI'iCId l (7l We ~~8.'\!Ie lWg&el\tOO 'dliU a ILganrl f« P1rod lcould be aninlpOf:itarn pl\ayCl" Lm. ~[)i.dmlilt}' (5).

imb ~i-I!a!1.er;l!~g~l OlXUI'S h~ ¥ariO'~ spe-cles of ~~amand~mcru olTtlfs:rnlporol1rll

d~ne""'aloo .d)yriJ~S: 'UI.e i!]H~i;l!lI~I~e (If ~ILyl!li!' '~OUlllUbliOOl, bllll dmCi!"I!ati'{l!~l~rtl1iC Illid!...bud O ~e alloM the fO:I!l!lllll.iaI!! of !1Ille£ientlrnle (.15),
ill:

first wcclI: ofrog,e.nmo:. .Mionirnl. m~.adlJl'~.mmvt,. Irlllt.v~i!l eritteal. for slIb·

thl':

n~W(IIt1!fride.p1.d0lil'l1is
pmli:f~m[o'nl dllrillg

is'm:nroquill'l'lcli

ilOSllIIPtport

reacn:llli strongly,. asilrusntat:cd by 8. ItHlgiru.diml!. !!tmU!Q:1llat S~Y!l I!iR(}jjl!Jimpl!lt:aIJlOl~ [pos[.,an~ptlla1.iQn (~!I)l!.co:~porn(ji!ng (0· tile
Ilier'iIC ShMd~1

mo:loc!.d~ arere· ~ibl\l:mr dle <ldivi~ ofdlC IllJ!'il'e anciwund '~lidEnnis 1(8). TIl~ecandiclsnes considered 00 in.dude nemrcgJll~im (.n, 18)., f1hmb:lJast growth factor (/9]1 Inmsfemn (l(}) and suhs~anoo P (2'1) ..

ooqtl~m divi.'<:i(Ul (.J~I. 1m n;;m.un.<:: !.!mf!tlear wlIlcl'l

~~,

d~iffu:~Jiltialiolll

~:,i~¢

{26) ('~~

2A, mJdl

c,m:

[n,

rt(:);

.t':.1Se.

:ha,qil.oo~ndlcmon.~

Itln3li1l

riJ,~Q~Y d~~t!I 'bW;~n1a ~. lre~u6d s!!!Ci1 U~ ill' rege~tes oo· fOnl1! dig~Is"We ~a.\!'-e ide!.~ri§edi1l seQ'Ckldi pmlei!fldm isa H:QMdlbr Prod. I and agm,!';'ifiI~ faclmfbr Hn:m bl~lai!
0011£.. [t iSilldlllecd.:ilifirn" 3;tl1pllffilio:n M;lL"i)Q.ti

al.olllg tll~ It(';f\,ii('J simatlll, and tlt~ ap~ [ill. tllfl \vooiDdl cpi~ln'!Ii~. TIn!:: ~p-m&'lion in ooih!ocatiOlil!ii ~s@bm.gat~d bj! d~!iIeI'V"41ion" MOS!: !J.(iH~)~Yi' (Il!e C~~ioBof ·Ilillil.pro!~~n .C[ID reseue .he d~lCili'!i'!Ji~ed. Unili blii!S1)Cllm and. Sl.IIp.pcm: re~uno~iQtl Ito d~c: dig[~s~~e. Resllii,ti .f:rtemifi:catim.l Qf'~AO fJJv~ei{1 al. (1 Uf§~nd l()j Pnxl 1. We ~utun'llGiI'<1! )l'e&lt ~.wo.tybridJ Sll:iret.'u wr~b Idw 69 "!Nt~o .add !]C\:vt Pi!'Od ~. !protein

rogJ,;m.e~

lltestmmtooU niche fur Hi'iIlbliL:'gl.lllle:rrattcm ~;;!b<; bool~ srud!~edl[uu.nsive::ly, and the key ~jS$u~ are the; !i~tle:L,e<Jilll]~lgperip1l!er.ll!lerve'li:'limdl ihe wmm.d qlidiemlls (oS}. Tire se'ii'erod WlJO!]!> re!r.ilCl afWr .a.1mlPU!.fli~DOl1 ,aJJtdlll1ilcn.regenel'atc baCk aim1£, I~~l~ ilil(M'll\e sh(;adl13lndinto the 1tJ~a,'>'I:C':rl1Ja\. A.wltoll ru.g£lt1(lral~M ·cam.1le: prevrnu:cd al"fl.:lmOS~oo by I~ilian:seclill.g '~lmspinal nerv'&S stllte '0000 .of tire ~umb~ dib~tan~~i1ol'1i1 :I)h~ amp:u!a'I~oniil>"i/{:J (9), the g~lmttm~ d]C' l!l!tl.d cclm!tQf blasl_e:Rl~1ct,1~s of {\I«LI~'Stn ~ del!1cF!i'~!ed ~.hlib, but il'he .gliO\!tdl .allld! div:r:sim~ of tiae.sc' ccl'ls depends on the COIlC\lIl.l~ i~Mlregm~.cmt~{lll oi~'pcr:i.p:b.er.d llXQrlS (ltfJ). Bo[J~, :motor .;:mdi ~nSl)Ji}~ rutQI:ll'lbm.ve dlis a.cu v.hy, and i~.isind~n~d'eliIII:.ofimpl!l:lselIDotiT'i(:'Of h1UlllliU~ ~~l.~ OJ', ./2)1, H.ilI [)g~tph.ernlJl~eMis CY! ..mcl d!ev!<!i!oo~ntQ ;;ii, :sklllWQ1;md,it cm~ ,eve!lev~ ~!he fonllatim!l: {If ~n OO:lopic uppel1l.~goe {l,3, t 4l .Lilli'! rt;gela,era~ion '~Dbrogmicdir ~lIlIe bl~l1I!1i1
Q'~ B~OIj~@mr6~r:l''l'IId 1iki'k!i[UI~r Bidtll>JJl'., U.nilr'BBi~1i (oIlE'gil I.«ridiOO. MWBl §i!Jtee!·, wmbn well: oBI. UK ~j)iII'i.iii(1ni lot Mot~!iI!OiJ 'SlruWII'e, N~llioliial ~fi!~lii~~te ""rt\t\lldi:cal R"~searth, lbe m~~. hU~ ~il~ ~ Ll!!iildorl NIit\17 1A.A. UK"

11l;l, 3). We 'aJI~aJ!y-4XJcro~¥(;ttkm~ .oNhe s'hea'tl~ 8 by sl<!!~ni!:!g fb:i Ibotll rlhG 0100.'dle Sdl~Wilnr:l !Cel~ Il:H[ilt'ker HNKI .. and the mAG w:as ,e;xprea.ro lim. dim Schw::iliilnee~1s but l~lOl ~llil 9Xm~ (Fl.m. 28). 111(: wound cptdflrmis was: ~I)itiany 1il~live during rogcncrnu.clll, ilbUit. aJilllI' day 10"pa, i~iiilae~oo i~l 1!l~;'!n.dI~lM~a,~ .a.~~h{rV;w! at Idly 12 pl'l, ~~d!~"g m ~e eMIr bu& m_ge (26) (r~t,l. 2C and fi.g. S4)., Ne~,'t!!i'Were (k:nflNB~oo.by ooU~J~gthe: spin.al. ItcrveS; ar d.1C bJrIlo'lMal. [plc.xw of dteri~1llt lk~'l.b 3l~.d thell amp:utalM en bad~ .si.d:C!.,>.'Th@ ncl'Wl 8hcJI'~~ [1m. tl:leirnl.l:~iil.I.'Q~l;n~b ~h(lw~dI smfOtig e'!i;pres.~ioJil !U I&y 8 1Jl.\\)j.!he~ nne ~h~thorl llle de~e!"V<I!,Jedside ilh.ot\V'cCilno incac!il{l~¥ (fjg. 3. A ami B),.li~leuestl!nJgly the ,ex.~Slofl h:ilOre wooncl. '€lPi.dl!nmisW8Srillso d~H)iI!tcl~liIt ond~c: ll~ •. Figure 3C sh.owsl!Ji l'o~1iI'1?O'\II(lu~rnage or li1~ewCfl!llw.epidoo:r;uiso:il Ihe tilll~CM.tOO: s;ide ,lnn]l. rliAG PQ\li~\!'e simas d~1y vl~~e, w~e~~ the

Cf;K1!!H!ilal!crnllimb :&110\\1100

riO ~liyi!,)!

!md

!'l1J

ID~pa rlme'nt

'i'lhl'$e ~'I,I!1I0r~~o<mlJMl!lu~ l'ql!J.;l.~!I' to thi~ ~\m~_ "~"Il'!ll t~lit~ (olu!sP'tl'nd\I!'Il'~1!! :~houM b~' .ad\dre5S'l!!d.E·milill.: j ..b:r'GCil:as@l!Icl.ac.lIk

{w:hlmut. N 0\1' C tenllihaal sigJlallal1clu:!Jil~£ 00" qttcJ:tccs) <lIS bah al~J wl~lilprny 1i!bmri.ffi ~rivOO. fIDJllibo~h llOmi8l1 rnle\l,It~irnb Hunbb!a,,,~OOIa!. .d ~fI :a seal\;hr~n~l{;nthli e:l(ltli<illl:l~hlllar Ugan.c111. l\'IItO ~oo>d ~(roOO:lll-~ ""'ere i·de!~ti~.~all ptl~. hivc:s _mOJ~ st:!'eiilnandi .subseotu!:'i!~t !Cmuw~ ,experi nWHI", {.Flg, ] A). Om:: was a. ne\li,q u1tllaJTh1.'ler of thefmuHy offLfItcri.or gm.clJiCll~ ~ra.t~.f:\s. oogiufllly de(]n0rn: by dle .XAGJprowifn,. wlrut<:11 isexpresscdi:n d~(':cell:tel~lg~and~flbe X(JJ·{UfJu..'! mdpo!,f; (f:~g. ~! 3; (12). 111es;~ pl'(Ill:lins 1h1llV~a 1 \'lingl,€; thiQred(l;.~ijn rQ~dwlliil~ ;;l, soo~~:~)!ys.igw!;li~ ~e!lQe (2J). TI.ley mre e1!i:.p;~~e4i!~ s~re~C!!'Y ,epiUl~Haill1td ~~ave loom idlcndf,i,ed .i1!S e~evmed. in vari01!lS el-::u:nplesafrodoot ~'U~d:hm,1f11n cmn.cc:r (24,15). .. Epiloi~.I~ggedl v,LlrnNi.on.~oJ ~acren.aUy ¢X'. pr:e.5Wd nAG iiHnd Prod 1 ·!NCre·foynd tO~O:~lP~ex log~l!he!tifl a 8ta!1iilau:d puU-d-Qi\!';'!1 as5a.)' (Fig. ~q.V!Ii~~tl Itly~(Olgged. nAG\'\,'OlS .eKpte~swd al1tei'lrnllsfeotim~ of manlluaJiilrn Cos ']' ,oe;llls, lit W8.!l ,t;OOrot!oo. and. tlli:m: dctool:OO.ifii, l~lI!m.oM.a~ Wlli\g Inwo dif[~IiWtI'[3j~~iOOd:i£sdilll\\CtGdlm !:lUi)·

Actii\11W.tilli oj I.,AG .WJ ,he(k:~r.rJnul'(Ml blafjr(}/~UJ. To ·&;~hll~[f liherwo!~il!l. !,glhe .. dyl:! !l~wt ~ln1h•.~

gla1I!cilUl<J11" l!!!Ma~ure-s (Fig. 3D). 'lNe ron.dude S ImJ~al: d~e Im.G I;i!f01if.l!iil1~Se:K~ed ~ndJ.'::i by niche n,o;sucs ,earJ.yin. rogmmr:a'lion rulKi.that C1;lIlpllL. skm. ..... il1l.oofih. ~ocat:kIlD8is: ab~ by dlmM'8.1ioo.

el:ec:IJ:QJ>O!iUecl. r"~~!\~tdONA iulto U~e d:LS!:I:d stul!l1fl .. (cia>' Spa. :Ill b'!i1il ~r:url'!en(S" Nd :fluo~m ~r:oichl (RIFP) woo soong:ly C>iP~. jill .ab.a\][ .3010 50% ofdJo m~l1i.chyw:wl.c{il~ :um, dl;is reg[:cm {Fig. 4A)andpBfS:isIOO. ('Or lip lO J wook.'1. We ~NP~ nt\G :rOOll'Jla ~bsi1in;:d wiiJ:h. lheN lennimtt ;s:~grml 8~Ue'!100,. !,1!]d the. 'pltl"e:i!1! w.ii1,S !:eadny deteci<l!li!e ~O~.l in ~he ,e!l.~tfOll~f!Ued
ceUs (Il'lg. 4.B)iil:Ildl al\l;:r

tmoonlll~3r .S,paooofthceai.lyrogtlllera~£', .Bccan..~ IIDlisp:rrooodu.ro !ippt.'8r:ed. (0 dd1i\i;ar thePOOlmll. tll'G;CthOlL'l~Y1' v:.s: de!l~:M.edl .. 31.~i.m:la1!lm~dll1lrigillt si:®., ~'i'l!p.ulatoo oodll~rn~j' <md. !]jell e~oo'OOpomk,'d the !lAO pl~lidl or ell'iply v,6(:wr OIl iii€: de!lmra.t~dI side. At :day S aner e],ecnroporn~km. w,e sec.;timl.CCI i~~le distal Iju]oo on !!lotS! sid~s ru'KI. stain&ill \1iI'ith, d:te :nAG !l'n.lilbodies.. None of du~ an.iirullil(lib:ilro,potatOO. w1~~, ItlI!1l00i~iroll"'OOtor

~tLon.tn

iililee.x~

RESEARCH ARTICLES
~11O!\:¥OO ~p~!!¢e iihe Qf!~AG' ~tive g~~!1!d..~ i~ !ale 'VQtmde'pld~~lnl." blllt" f.iveQ1J! of six a,liL~rllals eleclropommcil \!lith, ~ffile nAG plasHillid; sho\:vOO lhIeiltdt1t'll~Oil, of IlIAGposi'viw gJ ancl~ (Fig, 4C). '[herdore, th~ dcliv~ Qhh;iS:p:lUltc.iI~, hl ,:lJdlilltoGtvatecli bla')lnma can in'iclu(:~ 1!,'lt~ 'L'lleI~'i~!itllil~ w~inld ,~i&i:r,!11is. UIi,i,l; To de,te"~i:ne whether!i.AGi ~ ~'lOUe 1I~ ~~e detJeJ'ldence of Iimb fc;gcneral:ion,gtllJ'!!!ps
of @im~5 w~~ ~Qe!'\'<I_te(;f! on ~~~righ~ ~i.!~j <l!!~cl~~!'lMl~I),li!l<dW bil~mUy (Fig. 40). At ,~ "fhe n~'\.'il't00 I~h.e !,~fi1~<lll n;~!wWi,OO it~ CQ!~~l 1"":I':t" "I ~""''''''''I.. k!·,IO! ._""" . · ... :~ ~.. , . ~;'I':I·'h ",,1,1''''''''''''' iillI... .,t"I,~· \1.1;;"", .. >'u,!'!·I I~~ Il""": ~._.._... _1,_10."",,, __ " .'~.". fill led to ill'l.:..··g.eiI1li."iioll:e.~n So.1ille lUtitl"mJs:, (he IDt:'OI1IS may !1ulbseql'lenttyrregimICfilUl' fllrmn dKl level of liiIe ~lru' 10 !llilc 8.nn:ptl(atL'On plruac, oo~. .ei]~l"\ffil.OO. d arnolt It~\MI D1a£I~i'!J.la.'l 11!.i11dI~P fi.bro~~all1d! ~1I,uer tls..~¢ changes i~t <'ltop lIie"!ijJ :rto~l !ltl<lilki'~8 a .:iI"'la ·AI ·.·-.Ii __ -,. -- , - ,(27).. ",'L_ .willrn~~!'i: 1:<11 __. .ggj 1.1"'__J''eY! oo,ge_ll!-~Ii ._Ye!lel;'!IXLIt!SC".... elec!OOp'm~i'etill ~~~ dle veclOit l!ese~nb~edUte: ~efi Il~l JJ,l .fi£. 4E. The rig'ht animal has :1100

5 ~a, ~eri@hl

liml!), W~ dacltopomtecil, dl1l~

wttilil, nAJG p!8$illJ'llidlor wida, iC:m1"1:Y vootoo: TIlm

~illr]lrls
pm~llI
10

we:m a~,~o'l"i'tldJto rcgmtcra:ru, .and!! the I

oflill1'b
~M~F.ttt![!I] l"'ai3ii1()~l~tO~ :!lI,,"P~I!lUUi~!('i

d~y 4Opa, Two

up Inew!!!; ~

~howf:i at day 4!0 in fig. 41E. llie po!li~orl ,of ale inIHiil!~ellerv<llio:n!s tm!!te~ ~~1110'1 ydbw ~_!'; d

ro,gi,m.c'ii'i~oo. .on '1.I~£OOI11rol~d side, 1i:tm.d,1,e

~)o!pre&Sio:ll'I
bl;l;~m:,l:!lIlld'~~~Ii1~rn!iOll

om' w\.G 1.1M limOll.lOO. (J,tC: d~rnervnll1d ~a.~ p~ood~d oo.dt¢ digit ~~. We .m~y~cG~l!lI'!e anim ..l~·ofd!ff~!TMt bal!ches ail ,day )0 00,40 pa, and Iwf of lI~e !:!lAG

elootropmi'iJlted antm<lils sb>owecl di,s.it·si!age roglm.c'm~6rn) {f~ 4E). Some animal!> re~l1cralOOIlltOIlC :slowly :tilt!!. ~: 11tH ill~e]lli1G(JI as

fi~g. 1. Ildilntifii'UltiO!III of lilA'll pro1!!1illil as <II t191i11i1di~or Plmdl .1. (A) Y·east tlMI-hybriiIlilliS1iIlY iIlm,IJall1il91 the ilil,tflr,actfiOl:!l between niAG; oiIrnd~ro~ 1. (I.) (~Ul~!iI~·:5· Baye5ili3i!il phyllJ9enetkIIrEH;l@[ repr,e:seIi!1iIIti:ve lifllle;lfIiIbers of thE!' AG~alil1iLy ,of lSE!(:r'~ Ipm1reki&, higMigWiting lioA!G:, thLi' foUnaerrnJemJlDer XMi~riliiiJ(jlthe IliIul1Ii1iIllii AG2~ wlhich~~, !I,!l-regl!l:~1Iitedlrn ~ewral el!'Hlilple~ of G:ilnmf. (C) ~1II1l-mWiI!l<I~ay 'MIl!! lepimipe~ 1 tagi!1J!'ldfGf;ms .Q;T !'lAG ~Ii!d IProd 1 pillrifl~dI gller Ibac:~'.a!l !'l:,m~:ss~OIiI\. 1~,u11'11, !)onli!lI;!~ 1:i~$U~ gJ~lI!!th I~Ci.ac:r ('(TG!F) 'beal1s.; 2. I!IAGb€a!ds:: 3 •. 'c0fI1tiT01,1:18a~·s + i?rod 1: 4, !CT1GF ltI~itj:s + fred :m; 5.~ IIilA,G 11!!~.dls; +
.~rod 1. Nlote' 111'<1111 l"!rtO~ lis olilly IlimUred dowl'Il~:1!I La'lile ~i. .Secretion ·d~ ~G ..If (Dr)

at ,d~ 5, P!1!!, S<1ii!hl00 ~thali!tbodliil!S,

ftl. 2. &pre~](nl! ,of nAG afit:etillllfl1p!!!t.rnC:lf1 0:[ the lI:rkrilt ne:wt.. (A~IL.ongituJd'iirliill~. sootiiori of a ll~a~m·<Ii

II nAG

(glr~nJ. Notei:~e moogl r'~CtiO.1fi ofithE! lliE!rw sheath illiI.dllack ,of llle'amOn in: 1:11 e WiE. Th e dotted

(ells. G~s 7' (~~IsWIillI~ '1:!'g!ii1$fe~wltlma 'pi.asHilM '~r~~i!'lgm~ myc·,m!!1Ig~ 'IIIAG, er RIFP. ss c)lllltitrot. The mediulill w.as aniiJJlyz~d ,by Wes.-te:rn Msmn:g MltJI ,aliltl!ooy to myc. The central lane iiS, the IiIA.G' ~[ilIn~er:i sOiIll1l(J~e,fue lniQht i~the~ Riff', <±IlliId the left is the' m;ole~luir Wel[itut 'lII1IilrklH8. (1:) ~.actioo o,f l~y(·tag~ed nAG at 'the: .$liIlrnface (IIf' IPr,ocl 1 'tralii$'ectedmou~ PS:~'eru~ nA'&~on;dit:iion:edl.n;lediiLlin deriVied ajsirll~~[I') MIS reflctll!d M4°( m~h tmte PS 1~E!lt~filn5feded to, ~re:5,S l!fIr'cd 1.. INotelie: IPIlil!'ple ~eilctron
I~r.odurtat t'he II!Jile!m'bralile ~iDmdITi,DrI Ib'eiweelil. tile 'two {elI~s '[i:I~)i. S{Bl.eili!lr~ 50 jjm, .

on 1ri1llilflfernon

l~~il!~di~a~$ 1h~ posiOOfi of '!he: ,i1!lfiIpU.tatiOli! p!tliliU!. ~J) 0[0)$ :semo:Jil of ill IiIll M Sheath r'liI 0'31
l

of COil 1

l}~astellrlCll ,at day' 10 PI:Ii", tlBiinoo b JiiAGI '(gre!m]' • s th(l SChwaltllil1 (~II mlQfk,~HNI<l (r~dJ\ a!il~ l1uci!'l'j (J)h,oe-). (() ILoogiudlilillll. ~on o,f ii, I~lamma ,at miY' 12 fl'.:l,r ~t:I.lililoo wilh,mtibooieJl, tu mG ,[Ind :;hQWl~Q ~A~ pgsi~ gki fiidls (!il f~,gW)+ 1N:S, ~.!l!~ shmh: :BL, bilal~IfiiI:il;WE,. WIilIund,e:pj(Jj~rmis. S~le ban: (A) .200 fi·m; jjlill\; (0 ,250 i·jlJli.

on ~

'174

RESEARCH ARTICLES
w~chi~:g ~Ilgit !ijti!!,g~, w!l!~$S oth~ dig) ~ot ~ge!wrn!e,IJQ:il!liibly ~<!1JI8e Qlfd1!;) v~bmt)jin 1~lIileiil1A:Ge%press:iOfill It.'Vet observed !l£l~ d~cl'~ l!iIomuon of plrus1illid:s~I~I~{) a.d.uihlnmlm. .Limhsroseti~d by lilAC CiXlPrnssiioll, Wim': SJ3C.. I!h'iltud al~d Slaiji~edl\!!,lid'iai1llj~i,~ aIO:ifigwil!1~

ih§!r CQ1ll~II'$~<lle~!QO!f!f!'Q~U!lli!J\'l, Aner~~~in" i!~g wl!il!! clll!!Jtilx!d1r' ~,Q,ace1.y~@~ed tubflllUI'I.~lkh sDlllinspcripi1etill nct\ics, d~~l'!esOlJ!ed. lirnb s1lIowed r~w lm:belcd ~rafiile,!!. whereas 1m1m oo;illoo] limb \10'1.1,8 dm1t!ldy i:iIlffi'leivated (Fig:. 5. A and EI)•.Tlli~ ~$uH a.ls{j,il~di¢iil}~ tI~t I!lAG

dt\! !lQt~~~~ g~e: d!;!W~f'I,'ii1!iOO b.hl~.<;;~~'l11i!l, by e~h@:ncil~g~l~ r<!~~of nerve ru,gelle~ti.Q[!. 1l1CS~ Hnrubs were I:lsUiaUy IlJlmphiccmmpru:oo. with the contm!lrnJtera:loofJ.~diul!l (fjg. 4.E),. find. F~g. 5,. Cl'Iild ]),' shows Sli'lCt~Olil~~ stained '\V.i~l, 3ln6.bQtly t(l ~ii~y~.:dti. ~)tr~ri:n'i~nta& Uiii~M Th~ had! l~ ITt!!m;cie 'Ihiil~ Ilieiifili¢FVal~~d conir1ll~. ii!ndi i! OiP[J'OO:rs ~ll>l!t'lllli1e d!epl.~deftCe of~.bl~aJ1

muscle

Q~t

i~s im'!ervalion

i~di~cili SUbsliillllt~n!1l 1fIA.G. by c!e.!U'; ~Qwc'!,\'C;, 1i~8Jt ~h.Gnc~ reql!lilrrc~niL't'il oo:~upl:et:l(m of d,Ul fM I'D axis '\\t'i!:>; i~lCt in 1n!IR.. c aili~nllll~ .. ,aJlG at;lJ (}W ~!;,'J'{Jwlh JCi,,'f,()f" !o.~'("wti'w~ bkl!s'Iemo.1 c£tls. U is: difftcl,lln ~Q l!lll'lde~"(j d:~e elo'e!uslll!li:!eriyill,s: 'De~~divislom in [i~illb m.esellCI~yme ~ec!luse of ~he oon1plcxil)! of ep~nu~liallfII,escnc'tn;Ylll:lll)1 illflleracliJ:ms :tn d.cv,el!op.1fIl~l1Il 3J:d re~in.(lfalk!Gl {29, 30}. To (fulm:murm wiledlter IlliG i!I.tl'> directly o'i1llim,~' l:i~amCl:lila!1 cells M! Stili'll·,

n~s

(2&)

W,~S:

I!I!ct ~l-

!,il~

I,]i~ir: p:L'(!liferl'l:~i(JI'l, the

'Wllwtd

~pi'd~n1[!i~

IFig. 3. IE:yJess~ol1l of mA6, il1llfl'E! eariy ti~ilIli'1Iel1l'liCJ depend50@l1inlllerrvatioilil. (I\) Cr10ss seclif:onJ ofa Ileil'i'li'e ~tl!~g:th Ofl I;h~ '~li'!!i1eJ¥gtd:;jd:~ cat doilY pg\!ii!~~ (8) ~r~ss 5ied!'ool 'a~!! sh~1h ,00 'I!~~a!ilttatater;~~ de!llmat:e:d sidle, liIetJ1il :ltaillle,d rll p;a~rnle:~ wi'i ,alirtibcn:hs, to rrAG. (,0' wngiilUci~lflaJl :~oo ala 'blllst~fflill onJ~he 111llliervallBdi SEde at day 13 pa, .5Illtwlng n:A:G~po:5itive glal1lm 'larrow)'. Ueinsetsil.O'lHs two, 'gla:l1I& all: higher' In;I'oiigl1ifkati~. {o:~Secti::i:n ~f' :the ,cantl!iaLii:te~al denel"lll.awdl e~dermis,wi~h th~ amp-:utQJtion I~La~e (l:io1tt1'Jd lilt~) iiilildWhe I~a Sie;l'rIi'l.. .5Lt! ~@J bm'S: '[A)a:lla ~Bt lOMlJI J.lm:; (Q alld(D) 5001,!JIm.

w,~ re!l~(!!ved :~m Umb blaslemas,md ~e cello; w>lNre .dJis:soof~li;1d1 ~nd~lI()woo. to ,aUachlo ~illic!tlwe~l:!1iin sernlll."fi'CC~medlulwi before 1l:llti.ilterutmlCe jSili~'ledJil!lm (loilllaii~:ingi % seOOilrl. (Jilg. ,6A). 111~ elllltll!ll'CSwcm rcacmdl. UlM!.1r live ool:1.diliOin.~ with ruxnibody I~OIProd I, 3J:d -70% of dIe: oeh W'~~ sp~~fi~ly ~aialoo O!] d:l~iw ~~II SlI!r" lace.. n~ce~l.. were 'i!~clllba«;dI wr!ilil !nedilal

room em; 1 cdls

'0.1" \ltlUh.

'Iransifecwcli wlll~ it nAG ~plasmtd a OOlltml.P!3Sil1l:iciIL ll1c nNGprotcinwlti

If'tg.4. D~~iI!~!iYg,f IilAG p~grer(]ro Iregerueritting n~ Urn!>!.. (A) RRP exPr~~illtl at. €'illd 01' t~e iimib

s:tYml~ iilt :d~!r llO' I~ l~olrjUi(J!n ,elt d:ay Spa"

me

(I) Exp.r6" s[m'!lor I1IAGilli ~)~lli> of 1Ii.e limlb' ;alfiter l!l.@ttr,~poIiMiOO! ~f IilAG plGs, Irrrnidall day'] pa, TIU! sernoilwall sta'inEld: ·w;j~h ,al'ltibod:i:eo~ to mAG l(gf~!l!!1J. (C) Sll1liiO!i! ()if aJ rrAGi 1))$1t;iJre 'glomi i'Jllhe WE.r~r eieooro" I~CliratiOlil of :nAG pLa5:mtd ~nm' ';1 d,efle!¥ated limb bla:ste-millat day' 5; pa,iilllTldl .:malysiliatdla.y I,; IlllIiiI. (I) i::xper'iinentbl desigfl~or ll~s.a,ying

"rUIi el~dJrQ·

dcrucll'!d ~n the IT.IJcdiMl!llfll3:rii:mm1llOOIi.do~lil:1g Uirrldcr bod} oocl:llIc1rng Mdilmrurcdudn;g con.dllil.mas; as '" bamJ~al. 18 ItO (fig, S5)l The 1iIlI~ stu~ ulatliOl'i :ilmeK for S"p1'!~ C!lt!y~, 1t.. ,deOOnt~im'!ed by b!'Olli!.odeQx}'U.ri~lY!e (Brdll.l)' pu.lsela'be6ns. w,as 8.;3 ± 3.:3 roM (So' as ~lli.nnecli in cjg3ilt iooe,pciloo:lilexpcnilUoolS) {I8Me 81]. .tI.!l.~ cell. prlllflrauoUis W~ respo:nsiiYc ~:o MG; an ex3mpl~ is )i1ilOWf~ in Fig. 6, B ,fL11Idi C. 1111.",'L'iVi.~

de.~ ~-ppG!rlS, ~~~e \~~V IUg:;J( MG all] .re.'O'Cu¢ Ille de!teMwd ililia'l'tew!lOl) by <:!~ing directly Oft
blO1Ste!'!lal cells
ttl

sd.!l!lI!bne d1cir pr:o:lirem~.QJl

nt.1'\'C-r

~:ndl, IDiIlcmfOllc. thill it lt1.od!uates ~~e

depend~~l~'\~~ E:H~(UI55ion o:flIDbeearly Illgeilcrale.

Ol!!f LdeUiIiFlca~g~l·gflnA(; Ol.\HI IlS<9ndlbu- i1!¢ PO ~te!'mill1!,!i_l!t Prod, 1 has l!!ncilerlhl\l{i ~'B!lIit p<l:Ucm-

artMty of

IlII!1G 00

t~@'

d@ne~.md

I~la~ema. NeMG: we~e denelmted alnd ,a!1ilp,utamdll~ef,cml eiertr.qJl!lOll'il:"

ti(l~~:1iI
le'iIiI~

1~1gand cell dMskm ar.c lUnl«:;dIat ~,e IlnolCcl.!.laJ" level. We etw~sagc!l:oot :PI) M.cntuty is ilifl<illifus~, by l!liIe !p'IJlutarlVG: grn'Ciali01fl. of Prod 1 @ ililddl!at :MG mlas no role tn. spooi f:y:tng 'nhal
id~!~~ty bI[Qtr,llU!.§f <l!g;:t5 !iI~IIQ1,ighI~ ~OO p~ mote cell divisi@. ,B,~i"~mlll grow~.~,~ sli!]1jilqlated Y1l ~ri!tleHJj)al COnffQHb~om:; gf cells

'1!fIll! t(h::!i1e~rmd ~de with

nAG p.~lfrIidl DNA.

\i'ootorOI"

'I:) iRieprElfoenrtta.I:i1,\tf' ~liiim!l~$at day

,:U) pa. hm~'e two gr'oops ,~faiil Ie-iliperime-:m a:liltti'liledinl (0), 1lheY'e~" I~oli'll Stair lliidlicatel>me 1~~mCii!il (If
~~@

difflwl!lg in :pos~~iomt:~ id'ell~ity-rQlj' ~'Il1p!e '~fI, PD inlnroal.m:miOJil, ~Ilw:hi,ch a. w:n!>1 k,:vel. MasIDilllil is gm[~, {HMo ~ ,$hol!lld:cr :5~llunp(3'1" J2)-illlt!.
l!lIisiil
!'l;~.e, 3JWl¥Y.~

~lillit!lall ,OI@!i1@!V.atiiOIlI.

Scale oors:

d~i1Id{lnl Gil l:lIae~ID.llei1l.ct'l iJfd.~e { II!! <l: !'eceJtt &!iUdy o,f ~pc!'!aume~ IhlW

I~B)'d:lTldl (C~, 2:50!Jl!m. .

fllmlaliatl :~ (he a,"iiolotl, dle ,~c'.~ectkm the of bt.l.CI~LI1~ Iilerwe into <I. skin w",und pro~fided. Oil gmwdil sli,mlil;~1iIS ~o~rnt:lna;n ,ec~picb1;as~e~u:l Of "bull1p"~ stich IOmnp:!l m~~yprogm~ 110 [Mil limmuf .i3Jpi~oc: o~ .skim'!. L~gr:itil'l.c,j fIDU'iildle:

77'5

RESEARCH ARTICLES
o('lf!irl:!I1l!~~ ~i,~~Q i$!:ewQl!i!ld :st~~@ ss Iro r,!!lQ'I'kie deml.!lfiboob~a..'l]:s of di8p~e !ide!m;i~y (14). II~.is il~~hag Idmt d~nw:aJ. HbroblMiis e-xpn:.."'lS frod 1 and IdUIl~ ItBlis C:XfreS'l>tOIil,is IUp" ~C.gI!.lIailed 'by retLnoic ao.id (6).

1''';;0 lPRl",>ior~ lUUd,i~ .. (liiflAn ~mI~m~ .~ ~~~'II1i:Ii1I,00, ~lliii'j pEg..ilel~t. ~~II"l.Fii!'8t, the: ~~rllif!!~ A02. ptQl}~~n wa,s u~d1 as bOi,i~lm'i a }<e.;a_,;;t

1!.'Wo-1~¥b:rld"ssaJy <!Indlinll!!td to cO'~lplel'i:.with a GPI~!:IliiIC~'I'lored protein called C4.4, W;hl;:ub :~s a$gocia:l£d.wiil1~.m~taslasi!1i (24..33). nis 'P.iD~
I~dn ih,ffiSj~'W'O L:y6-ty]Xl GOO1!'i!bm IniHil $iii'C re!.M.cd im S~Ii)J~IlI00lo 1ll1mki~.~~-I~y~pt<lSUlir.lo.~en <!iCljv!'Ii!:or'\~e~tO.f (34,). The lieW'e¢ ·ofrel,attedl! ~}~s k~WCiCill U~e '~ilroo-d!~~~le!!1sior:lai s!!nc~ures

It! ~.~.~oofld ~~ 1m. \V~'l rg~d!@tQV~f:,ex~'JiPl'! 'Oirrthe XAO~ 'pro~~i~i~l .W~y cle!i!!v~ e ~e Xe.i'tOptfS Qi'I"~bryasceuld iDl:d\;ICC~fom1<l~iol:l of aJn.e.~to:Pi(l (]l!rn!!l~t Slruld tim! llXPlil'lSsOO XAG2 (21) .. We; fine! dB:e.'i{p~IDfl of I~AG iil.dij(i~ r~m1~.ltonhU\..G~~ti\i1:l g1.iu1U'il Ijl~ o il~ :d~l1)el\ltit~ [j.mvl\1\IOI.i:n{i epideWl~.5, Alfiei' <t!tlpY'L.1IIioo. r:i!AG ~ppearg IfhiSil ~!lUi!e Sch~!!lri ce~b of Uie dli&toil ~e: sI~lI~ and I:hen .~R1.g1:!lJtds: ~~e ir:l ·W'O'IJII~.~iP"l.dil'il1nis. ~~'.aiXOJ\fi1 ro;g\mCrmiOOl is i1Pre.
VCfiil'i.'Jd dcoCli"lilMion, ncid1ct ~lhe ScltnV:8jli100U by
no, Om

~f~PGnd~~oorreg§~e~~i,gn Qff,~<l!g:~"'i,g.clijQ!1! o
,de\'e'lQPB1II.'TIL .~tW !:e,ge!~em~km, the <mtgr:owth of lJiIe inH~b~d is nnt df.'P(l<l~eIlt.o:lil ilsinrn:tvatim:ll (36) .. NOI1c1b6bs, dil!Cin~w~:h. of dIe IJ.~f'iiiC .~ cri~:tca]fo,est3b~islnbr.~.we~llim!b·
~'l'Ii.IZ

~IMlSIi!lBS~ lnll,,!! !1JAG is[(;lI,~OO .tzy tho¢ di:S!3J~ sil~ <lm.d .~!ldy~ ~~elbmla~Qn (!If ~an,d8 ~!'! Ule wound cpid:crmits. lt a_Wei!l!'8d1Ji:ll i!lle sccrot,oo of['l'rod ] and C4lA dOlilmns is 110l yet. ~lved, !lAG "..cis dil:cicUy em d1e~imbb1as!elll<l1 ootls. U: Il!lut ~CilI' l~og.,Cit1ilClttlhesc rcsllil~.IS sl:1ggllSl that I is lInc.!ca:r !how IIDiDer,cgctleratim-.g axonsaet .ou rUfncli.on.8i1 IU'VCf90niOllll b~[w~n }'l.JG :pro~eiilflJ!' aIiI'd, d~G:!lheath ('iictls. 9.ltll{mgh. th.~n'(lll:tlhl"3ite: ~brl:uD. 1~Ih~sel~ of :Jll'mill ~ys.rich Ipm1(l!~I:Id!crnW.lt;;; of Itl.m.l'e~lLllin ils 3. eandiidakl,in VtlJW ofilS .~IJID:pon'la:!l,oo Ibr ~(!l]il iln[~r.:aeillons (3$),. 'fh~ l!ll~rut:l !111lo/00: OO!l~I\'M.

:gJancf!LI~a.m:ll~io:l~

is

de!lcctoo. Ou,

1m..@: I~~I'V~ {b~~ln(;lt~nC~j .:M;~holA/['j. ij~L'jI~.w:llll dte 1ml:l.~ll1II!Il;'Il~iOl'i GX.~ri!~eJll<; (H~ a,'i!glotl !~aJe (J7). The ld~li~C<1:tiofi ·afnAG ·off~r5 iii. !'t~ qppoo!!'I.u~~lt}~ sh:_ldy Ui.e rn:ed~a!iisliTI!s 'U!fideirykig 10 1i,1iss~.ti.":h. NGrvc: depLm~Rcc of .c~\eml~.o.n is COIn~w·cd in :pl:ljl'J.og_eil.y..~t hss beci~ ~rudjGdl~lIi. ~1l."i;·nerMiio!l (If ~ml~ fl~:'lI fin. th~ ~~. 1;).1 in

eatfuSh, Ute <If!l~''of crinoid ~!m.ac'Stle:rotdspeci~ ·

in edl1in~:xl:C!'ms, and !l"IeOOd~ 01.;"~ in aru.le~iM (18, 38).. !:Ia.~l \~bmte"ppeJldllges. I Ole densiit.y OnmlilCI"V3liOlnis: ~owcr lhanira.salabmL'ndk~rs,
amd Sirng:er' s:ugg~roo 1t]I~liI1nis is. aJ p.~lnruy de.. Ulrrl10UITI!DU fnr lillie loss ef ~'Cgcllef8liva' aiJi:!.iH~Ytfcr ~!'!iU]ipl~ in ~n~!Il~ (9, 3i9).lliis Il)'po!lt~is oo'W ~!l1~ uJ!hkclyoocau..<>e tl1~ .meo!.lilcf!,'llr'" iab~es .1!p~n(~y ,curU!mn~ rt\ge!J.emlion (I). His uotaMc aa,a~ I~lhcc!X.pressian of.' a s:iI~glc pro<le:~m. C~il ru~u~ limb regel~crat[Q!n. ill an. a:du1t.:iUl.im2l~. (F~g. 4E),. 91ld th.isiliimjing l!l:m:J:illrJ.~nCi> thot tltD hl:1Si~III.li!li~ 31~ iI.i.llOiOQlltOllL!l unit of or~lli~ ~ati(H~ for wh~cb 1~Ih~rei-" ~Q ObVto:u..~~lanl~ ITIla[taf<l oo'~nH.e!'JlM. \Ve have sl!!ggeSllJd l'Ii3t o~e epprcaeh rOif r,e,l:!!lIl!lero!.liYc med![c1.l1.e w{J~iMl be: to ulildC;:ir:s(al~(I~he spccific:artLO.Dl of the:
bll:!!sleM1Si al:il~c.v~~ of dictruil d~8l 'WUukl. 81.low it ~.o 100 cngim:mrod! tlil mammals (I). Tha kDca~. d~'l~vet:)i {))f~mli~iv~Ii(;Sl!l~a!~o~ :sll!jclii .a.<i IIiIAG

Fig. !!ii' 1~E!f\I'.~!'I!iidi~lmll~l!llSde ame: d'<el1i~ii!m Tii 11AG~[u@r;i lJm:b~

Re:5I!illlea Umj~ll weroEli!IiI\i!I~l':ditllerg the l)o~bmf!i!1 iliua~DVat~d lill11bs:.geUle;ra~~ all Ini~!rad'il!5lrulrl'ill l.eveL.SernOflis 0:11 lllllle:rv.irted (,OJ alildl ~(llI:ed (I) regeiiiE!rate 1~1inb5 were s-tiljinli!d witi1il1miboo~ til iID[l·tyllnedlmdltJlmin. Semom; d nJii~ !iierv,g~ (C)a~dl ~lJedl '~D) l~mb.s

Wi!irlli!

stiiltocl with amhld¥ to s!k'.@it et:II lrif'lyo8il1lU ·to laiJel. musdl:!. Mi., mlJ~l~. SGiIe bars. ~oo.~m.

coU!ld

Olen evgk}c!b~m<lf'i(l:ra ·of th~

<[Wlmprij~

me

!l'lI\!ClQ_DleSw:i~[O"~l

idle !o1~d Pm! s!!!bseqrJ.!~~l

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(;1'1)04).

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Rem~liIiteSamld INotes

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IFi,,_IS, Am'llit¥ of niAiG Qn Cl!~wret!l newt 1mb bI~s.te;fmll

allIs:. fA) BIill5;mm;)~ ooll:5;iiDi dThillmiltted !Cl1:ilb..lrle at 10 dI.aiYS QlfrOOr' p~~ti!iig,. (B an:d () Mk~l)~ll m.!ltums. of bl~~l~ (l~ii5 ~lila1t WIH'B oCIlll:alM:zsdwr S.ph~ entry IJI"'Clllilotl@d by ~lS.)' mnlrnol. [OIll@emiafJOO fn!S7 'G~m'(lIln.diti1\ooE!d mI.edilmJ Or (() I!ilA.G·l:I'ans:Fe(teL'il! m~~1I'li'I pr'O(E~~in parg~l 1li~ ~~U5 were' ,iJlIise ~ab~ withB~dU~llh::oo sta.tredf:or IiIlocl.ei ,and 'llblrle) or Il:rdU uptal(e, t~eDd. :5ca~e:bairs: 'W 200~lril1l; gll1d (C),. 1mHil>

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m9100t

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;~ul!s;arslJi'velr-i Ililfer II fare 1000ptlil'l!!1lnllzy to monatoo the radlio .sky fll,~ im~l.It'llwe' burS-I-like events withl 1ril1l~~~i~eoolllci dlll~ail!iollls. We <illllaLy,oredan:hwal Sl.Imvey dClIl<l,and f'mmda 'O-janllky di~fm:ed burst, less l1a!fl 5, !1!il!Uisecgf!ds if! d""I~~tilQm l~(i(:!!fied ~Q' fr,g!1lilt~e'~aU .l!i!Ia!g~~ar!i!:. (lol!d, Tih~ hi~st pJ,opries i:!lf~.Y~ag~ilr!:st,~ p~~h;a~SOC~OOfl Mth 00 r l~alalW gr th~Smal ~;g!l!la!iik CW'i!.!dl'CllIv!If.lm ~ m(ld!~bfq~ ~he:~ aecUofloonOOM; lliltfle: UlnN~~eimply Ulaltilh~ bill'st 'is less (ha!iII 1 g]i!i'Qp,o,f,~ dri~t:lnt No :ffiiilrther hur.sts w~re :Se'11111i~1!I (1 lim'IlI!'.!;'GfiHidJii(J!rllIi. ooSlmtltieffil, 9 will:1fri im,plj~ tlll~titWii5 ill sin~llIi~a:rr e!iel'llisuchi alii a supernova, Clrrooa:~esljeliKIE1 re~~[jc 1000em~ :Hunidredsaf ~f1rml~~ar of 1'l\!"BIiti lCOO:rd COCUIU e'~ry ,clay and., if c:leHted, Ilallidi seN~ as m:51m1Clilbgi£l!Il~. Ipmiiles;.

~1'C3~(}1" 1tIlI!lill 4 \;vid~ trn-leI!I~ ora. mallllmd m~oo;ng '~cch[li~,!I!IC O;plilltl!Zcd f(ll"pu~'>t': wMdns (7) in dJe ~ng.e ]1)0 ~OOO m8. nebum~\lt.t\ao; d~1)(,.tIW U~dial1l bl;.e!~eu 24 AYg~ ..200!1 w~1.'h DM = 37.5 cm-]: pc CO:!~I:c~}()r.aneO~~yllil !.hreene:t~hooril'lg beams (:fv," I)wlldl W1l'>~oo.ltGdI _3!;l 9Q(lnl~ofdte [leultrn" of Iililc Slnal~, Nful,gclll:9nic ClO'U1d{SM.q. TIm ~lldSi2 c:..n~mb.~~.ccl lh('lc:;:h.ru-ae~OOSlicquadliiil~Cd~lay asa n.me~i!On of radie f~l.mllcy U~~g. :) ~~f.ilOm 2 di~!$i(l'l li;ly a: ooM ~gl1~ ~ed pl""~<l!<lIOr!ig, iii(_': hO(l of s~gh{(~')..Aoo eV'ide,tll \1I;1ru;: II significa!Il ,e!jfO:~ulio~ of ~uillse widlIDIoooo.Sl> (hIe observimgri:e<!liucncy band. Tire bcha:ycor we Q~rvCld!, wbCitC dle pmscwid.lh J,Y '!l'.'!, • seaies "",!JI1il1 l:ooq~lI~ncyJ' u-'" .l8JS "CC . ., -, IS 00l1.l!i.~m. wi,1ih IfliL~lYwid.lh mr-Q'lmio1!'l cl)U~ fO
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'iIW' 24:944. USA. lGBlilw (or divi{!~a~dJi;spb'ffil~. 'Ihu~l~, .~ gi!,'e'll. ~n I~ihl$ kl.roph)ll~cs~nd SUj)emllllpw'iin-g.$wirof:Miile UIfilWe'r:l~~!f ef sll.!~ing ofll:i!~e !'i1.tOOri<!l.ln b:rief,for eath TI!!~lilno~, Iflal!!t!h~,"" 'VicjQ!:'ial 3122, A~slt~~a, QiDleF!:lrtDe<Mll" .he elL'.c1s oiriH~:m.Wnar dlspcrsiO'.Il\'Vefe meiii~ tit Plt~l'cs andl As't!l)I'!OO't~, Fr;m'Hl!'l o!!ild~'~rsh.a.U mililin~ized fur 183 tlltilli~ DMsin. dle mllge 0 ttl (ollege, ILa f'l(a~ter. PA 1,'1'(1)11, USA 500 Clin-J pt.'> The d'ilta. wtllre dtl"tl ~ItL"CI for 'Olio t~nlll1ll rorresptJllId!!IlIQ!' :~hol!llJ!l b~' ~!lIre5sl'd,. E-mail.: ol!lnc.:m.lmiml!f,®rm8illl.\WI,i,@!1lIu iiiidivtdi!ml ~llt'lBS w~tl'l ,irignal-ll}~Ulois:tl (SiN)
Oib~l!l\'atol"!j'" Green IB~n~.
1

sisn<1ls r~]]. B d:lfllrem posilim~s (bcllImi) 01] ~IC ,~ky. 110 daWL foolll eaeh 1 beem w~re one-bit Sm:l'P~!.Hi. IH/eli)!' mimseoo'nd ovet 96 fmMll1Im~cy CiWlml('tm s:J1I!amll~imga oo:m:l. 288 MHz \'li'kle, I~ililcn)()ooo..~ I!ellilporal ood ~.Iilla1I!1lS!)tutuOl~ IroqlJi.~d~Q I.l:n,ambii;g-.aol!lsly diS(:;n~llilna~.e b~ il~o sig!lllls from. 1111!ooh~stial s(}tlrces ~v.i;,et!~sh{irl~!JLr.l1ion a'3trof.)I~ysiCI.IJ b~.!fsts ,a,JIldl 'poop@.S<l~c rthooll.gh OJ. co~d iOlllbiedp<la5!l1a.CJ'f ~e ~m'eslri~1 inle<ufill:ence, ]!~d~,illCY have l:ecen1ly ,e:l~lroll$ ilb·eF'Iuc~'eacl~in£ the lele.'iCOj}c' TIu;: beell s!J.Ic.tlessfuU.y mfnC'd to det~l a Ilew gal~~c plasma, \?{,I'licb e:."lists wLd.ln omt 'Gamy 11'0(1 ~n !L:;Xlmgalaetic spaoe, laas ·flI ,ruCU;l(f;li.veilnx:iex iliIa;~ j:i!QP:IlI~31i00lor hrllsiCftD;~ 3£OOciatoo with.lntatiing rnl:LruOO1ll ;S!:W'S (4).nlL'; !:rue iit wT3liili]IDn beurc, d.epcn.ds OOfOOo![UCllCY.. As. a. [CS.ul,t, 3my ['ad~o h(l>we-'i!'~, ha~ III S":"lit'bmamuially higb£[ l.nfmoo sign .. ofa.~ropl:rysaC31!i)cigjll sholikl. c~I:tr~,a '1!l i:!Hergy (l\!~U:~ tWm~a~l!;Scl~ ,aIF!~hM f!ot. bet:!~ q~_dmttc sMft in i'~~wl 'thli!iC~ .<Jj. ~rl!cti.{l!,!:gf (lI:bllervedi i[O IIq~t 1'!l'iis bQ!'S~ ~l~r'm.'l; lrepref.~u.cncy. wilhnh,eml~:Ylll!.lto;nQ'I'i.'W! beh,g ~e 1n.~e;gmt~dIOOh.llllatl:density o:,fftee e:teo~lS along sents lUlle.mreiy n~~.le;(rtomenoH. dl~ :~ineofsigh~, tn.OWIilasdK) dispersion Ineasul'e (ILflVij. F'ILIU,dtlLai!is Qrlhc:d."LOO.Ii\rlIll{l~ion.pl·{li!~duru lD~,pal'1llli!'lilIt 01 Ph)rsi 13., wl!n ViiFginl<l U ni''I@rsil)!.Mar'g:~n. ~OOjn. W :1: 6506, IUI'SA. ~iNiljiJQn",l Radio As~ronlNl1i~ III OOQotmt Km ~tli8, llIlfoot, and to !;~~h fOJi' illoolk".clecl: i!ldepaKiemt

dCIcct, bllu [hey can 'po.tcn!.i<l ilYJlOO'vide illSigJ111Sil:~~o ~. wtde\!\mict:y of astrol?,h:y:rica~.p:llI;,momoo8J (I), Of paftimiar i1l'l11l~t is l~iI'I('lde~OCli(mof SbO:lillrad!o bursts, ItoO'IMre 'I.lnam a fllW mi~lisooOXlit" III dtl:~!['Jn.d.1iffIt rnl1a'"y be [lirodMOOO IIbf exolic evenli'l ~t C:OS!'!lotogi:ca!. d~!? l~ru'!.WS, sueh as Inerslng f1Cl!IlI.'I\)!] S~.lI'S (2) or c'VOIlpomUIlI£l b!.Erok ~l()oo.s, (3)1. Pulsar 8'!J.1I"'1'e}1'S ·rue c[l~lttly amOl~g dle: fll:w moordlli o:ti'lhc: sky ,,,.iLh, good. ::;.cfw!.·iv:i~y to radio bU[SIS,fhlllcll d.u~:y have:

f'I.'-_.~~.!'ii.C!l.

_.1.....r.uli._iO

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dimC:lI!i~

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Th~ blln'St was ,dl!.sCO\II!!100 d!!!ril1ig ;<1. ,sC<:Lrch law r,~,1"!X 1-4 (9)J~11te I!tl£!'-b.u:i.k srste!l1 1'IaS ofa!:'Ch:iv,[ll data, :fro:tn ,~1.4·GH2: .su,rvey [I r iIl11(~ fin!l'c froq1!!ency ;imd lime l:eso[uHon,'4lIlldb, elL"Cli\lldy sets 81ill IIiIppill Hnilit ~Q I~i!le ~lllrillSiG Ma:g¢llianrc Cloudis (~fJI t:ls:ing theUilm,~~ib~l'Uil. reOei'lill'lil oil'lll~~ 6~ml .Parkes .bdLO 1ie~csJ():oF p'l.IisewidthU'"",. = .5 1m., we rcp~.liit IllIis 1(6} in AI!lSnf£l,tia The ,SI!lNey oo:D1isisl~ed011'209 be:lo:w by 'film f'!a~milltiflr Ws = Wid5 ms, NfitC I!jl['fJ~il muke~y [~ihle; ln1ml. dte: itt'lmll.qic wid1!h ls l~li(';seo~po:irn1tings..Moh. ~a;!nirn:g :;L3 hO!lIrg,
Dililfi!~g

'i[!ln~tcllar

st:~,n~ri!l.g~~fijJ] Ko~mQ3,,:rorov fi'Ov.-Cf OJ,

each pointi~g"

~11;l

m;lJdtioo~n1 roce:iver

could be !!t!u.ch· sm:otlie:r

srnUering and.
,\~ mini

Ol<l!]

lir~..;:<1 ) and &~Ilh .. wk'hb 'WC' observe!n, Fig. 2: >e res!J.I.llsIi'O][l &'ecoIMb'inm.ion of h~]iJrga!.acttc
Oi~U: i.n:snrmneiilulI!ion,

o~e"oo U,e.;

ool11m:ate Ih£: fllIl>l.

H1iIO \V'3iY$.

d!l-mS~ly0 t'

the:

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.Fo:li' ~1fiI~ :Sl~nl¥>st

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tlz~.!'~Pl U~e obscrvi.ng sysl!e~n, we !n~e ~. of the fad aa·~]lhe i!Ltc,g!'o1i nl:!cwc~it ~!im~ s-eu>tI:te l1Jie~mleve:ls and. ~~fCsh,lIds~s aQ)liIlog, Willen, ~xpo,'>ClCl~Ofl sol!lfCG:of s:inmgi!lil comparable ~o

(iet;ocn:.1(i!'II"\'ilhk:l~ s~ltw:a.reddH~

th'es:ystemeql!llv<1Lh~l~t 11m;:.d~nsity:, .8!ll aboo:i1ptlor! f~I.I!IIooin. th¢ jp[-.Q\f:ile i'ii Indy()~d da1l1!. call ...~ .. ; ~A ''"' •..•• """ws_ w illSUm<li~ 'il- . 'n~-'.·"'t~;1 ""u~t e__ .' _,WlL _~.grn .'"'"' I" •. -ill'~fgy. F9'f ~S-m~ bllJrS'~.WI; c-siin~@ted,g~e p~ flux l . '1111\ u I'!" to lC._ 4v.·J'y (~JI ~.,I!,y;;;; '1.t1r- '6.u In_7- nZ, -.1) uS~I'Ig ~1'
j ,'''' I~ ,JI -

the d~i.e'ti.onsh[n ill,e IIH:U~lh.bo,"ng berun fXF siit.i.milS,. 91ild.lI~tl,Il'~ea..,i!.I:oocl~sc ,or ~mmn[ll.l!tliboo-m. ,~:illllm .a;_Il a. .lTi!lf~cUo:n. afolI..aw:isprnsciuml, (6),Wi$ d~II~llJil'lin~d d~~ PL'l$flIux d~"msity lilil'·~ <!Jll!easl 20 Jy.We ~Wiereifo.e adopt <l bU!'St flu.... of 30 ±I (I ly. whiC:h. !scO!i5islent 'W.~~h our miC:MllIre~n~ll'i. :rill:' lhe; rer:mli Iilll~gdiscwsi~o:n. Aldlou.g!~wl.'i I.\ave o~lynin~~£C1imf6nli'ii8it'iCii~1m. O tltD nUllxdcnSlify sp(lm:ru.i1~. !'Iii Slb':Ci~.ii~ Fi~.:2.

777

REPORTS
1~W!e ~~15~ ~~~oo~5i~y~n~~~e:S<1!' l~he!Q!!;!>!>C5t ~~ q~el!lc:~~ Qf 'OOf g~~yil!!g band, This: imp! ies 1~1Illi1.1~,the Hw;:,density S seales with oi:lsmrin,g freqpcu,e:y / as S 0:;; J --4 •
~tis '!,ImIYdn:frfnlcu It In atl:r~bil!lteI!Irl.isbuu'Sl to al~jllih,;[igbW 3J {j~~ez$lialg(j!~!'C~ l'h~ frn<!i1Iel~.i;y "'Vi~re also se ....~!~c.!rQrptllriooic rll,di(l!J!.w'b~l<; YSlng :5tili!!lI~~ tecJmiq~es (9)wi~~ m,gU res~I;!s:, The golaotLic la1il.me (b -~U!~) and Iiligh. DM .of the burst ImaJ::e:it h~ghlyimp:ro'bab~e for IiiIc OOllifOO to ·Ihc.loo._~~oo ·will:h.iJll OUi Galaxy. 1J.11!: We havc e::tlclwvdyscareh.ed f'Ol" subsa. Oif ~~I rnd!Lt!pol~ fll'Ol]1I d'i~~eiti:g'l~:iilie :SlUlii'OL\i. l'itOt'll ~'I~~ ]tl:ld~~ of 1llilt1l ~al:atli¢ di~~Jiii;~!iI!ttoti : ~l]cludil1!:g th~ ()rigi'~! d~tG(;IiQPl, II'h.ere \;"~~:l f~e ~!~trofi.~ (Ill) iJi$diCl~ a DM c(l!ltcibi[ltio~ I~l jjJf:a7~!11S i!~ ~he$U,q!\r¢y dii!ff! iihall pgi!iWd of O!l!Y 25 cJn-.!I pc for mis~ine gf sight •. ~.~ fa~t, of 1!11otel:iilliH lI700p'lJls.u~ CYIWC!~~]y wifihfu .:m Ol_rorilillflof Ute !W!llillfm! bLm [KI,Sltto!'i!. !mown, il.OU£' of tll~730 wilh Ibl .:> 3"S~ h.. as Tlu.1se !il,lbsmlaniOlt~. M~icia w~silecl ,SO IlOlrnl, DM :> 31501'1:.-3 ~. l1le; ID'M. is ailS(! far hLglltr 'W~ camoo. OI1l~ bli.'twcool, 9 JrnfllC aud 2:-4JM~Y 200,~ and sh(i!\vOO. ;mO sigm,i:ficrul'~'Ilru~IS. In Ii~~nany QifdlleU~ kl~lownradio I1l11l!s:ar.sim,b~ Ap!'i~.:l007 W~ ¢~~~d (l:\!!t4iO 1'I(litlll'S ~ffonO\l'!<. M!{!.lJ~~~ani¢ Cloml~ (5)1 'die;l~~t ·of \l!lhid~ ~" ro~IPSR JO!3!-7310 i!~d~c: SMC wiMAlDM = lI!po'tiit.'Jem;lioJls with the P.;;l;rit>e.S 1!~1escopeat ~A GHz w~rth sinri~r !1e~'I8utlvi~y to Inh,e arigmal 2G5cnf1 :~c. Tile odw:r f'01.!f'knQMl Gidio IJ1id!!<!!~ m the SMC IlQ\le DMs 70', 76,,105. and! obse:l'Val!iou. N'o IOl:lil:S1s: '~vcre fmll!win ,I}, SiC<lrch 12:5 Cl'lnl-3 pe, Dc :hig.lI.DM ofPSIUGLU~7310 over 'the DM r,mgc 0 [,0 .:5,00 CI1Cl! Tbese d:cdk~atl.'lcll [OnQ'W'llpob;rerval!i.onsi:IiiJ)p:~r!:lcl I:lia 11.1 iSaillrihl!llOO. (5) loilSl.ooa1io,1i'I. in3'ff1. H I]re~ml. th(l ~V'Gm !It!It~ ~inll"l i:m lass Ifib.ru1. .0.025 hOl!lJr:-1 (1fj~.ll W~ ~lav·G ~n::rurnanGd areh1vrnl sU('i,/GY data I!~ lool forio[]i~d $1!JlI!,Q(;tur.L:) !\11;1.d~ ;)8 'H~,tI; forbu~lO;: wul.h. SIN >6 {i"~.,.;;l;.I.4!-GHzpe* n~ dC!k<;ily ~~I~l!'d~all 300 ndy). n~da!a fil!ul~C!H~ or H II rc,~;gm.~ ~h,nool!!i~d8:h:ui~~Jy cxp~Ol.lnthe: ~!l;(I!ln<l!lOul)' !:ar~ii;:DM gf the b'~rsl. N\Q Slil.eh. fClirurcs arc:a:p'par:oot Th.e sornro,e ,~ics
iij!rg~

!!;If the Qb~:vv~ttg:!1,. nl~king it vkh:!i!l!b' in~[IDISl!]b!e fQrgool!lnd·,~~ed. ~nm~m~~me~ l~ .tQ respolilsiM,c for a source ~ru.~t:was ()Il~Yd~tooted in throe llclipooOOl beams of Ihe'poii11iI1lS..

di~~'~i()!i'i

~!'ld

p~lsl}owi&:h rr~ ~:eliLcyev(llil~~

l!ioi!~iM'giJ!e for a oOO"'~lk; gr:iSh~. It hi: VtW~ 11!J!'l~ iilely th.tt a. S'i\'ep~-ffe>q,l!ill!j:C:y ~!1.Slllil!IJeI" oould both :lfnimli.clht'l oakl Illasl'Wil dlispersicm l\.9iW 1.0 l~igb accuracy (:~LlC fXg. 2)1 and have a. scat~
hlfhlg

relatiaa

CoOUSist13iU \l,I~.dl(h(l Ka~i'W.ogolmv

1~·O\'i~r~\V, .Furtll¢ITIiI(lI~"t~~lllritt il~l~ul~~ne~ Oi.fiJoo :repearll'J, and 'lbi5,wm; l!he only dis~!'SC1!ll Iblll.r8~ d,e:rectecW wiUt SIN :'> l'D in ~lIi!,e 'Hl;;l;ly8~8 SOlllroes with, IilIJ.'l< dcns:iti,e!! gro9i~eJi(b:lln -~: Jy are ty:pk~al~~~ delootoo.iu, nuJlIi.p~(!: r,ec:eiveus ef I~II!I!(" n'Dl!lllii;m~m systein. AI'l.hQugh Ul~S is {oot'; foli' IOOth OOIl)~stri;'l1 .iII.td .MlJ\opiiy.~;,~~.s'Ol;lre,~, 1~W!le 1)1:!~oopc: had! ,a:!!! lelCiV<l'lionof ...6iQQ :aJ:. 1111;:

or data, ffO!n~lnno!it

.3000 gep<lratept!lS:~Ho!ls:.

'c.

or

3,15SCfllllh fmiin I:Iil!e center of th.e SMC. pl~.ci ng it oil!ltsidJil an klIU)Wi~CC!i~to:urs.ofradiiol l.nfll1lf.Lxl., opli~aJ. and Iltgh.... (llil.~~y m'li'il~siio:n.!'rom the:

SMC. I'llili!!.w!d 'U~~ll~lll~l DM S4:oon!g~Y,'i!!!~:resl U~t ~~:eS{D1!lroo is wei !bi::yan1dl ~~!!I(;: SMC,~li,llilich
He!i 61 ±: 3 kpc
m,W.DiY

:(11).

burst 0:1' ,supcr~ 1l0¥8. ,explOS!OI~ is ~}IIOwn at d.\iii c.poch or pos:!.oon •.. mdl no sil.~UlHlcarnll g8fl:lltl!:1J"~y 'CVeillS \\I'l~ d~IW:~dIby Ul~ n!!fdlltli~~'I:lliIfi~!a:~ N~t~ \~ {l2 a :13)1 1!!fQu)Tld I!qelime ofO]€: rad:lo b'll_rst JI.J(;: frlj~ciiPll!1 Gal<l!."'YCaW;lQ,g Woe (14) ]\;\,'ilS !!eareil~cdro:.i I~(el~l'iil] ~lOSISIO 111c blllr:HcS()y'_l"Oe.

NOp:UbiLshcdlg!u:mnil"'rny

1he iW3rostCflJl:ldid@:~e (POC 246-336) is 1009tOO. :Smlrcmill$Oml~. Oil' I~h.e ooJ~iinal Ijl!lID'Stposr~ion, but :Ihc IilQllde~t\Cli.Oi~of tile Ioilli':'ltin Ul('lliloMlml
SO'~Ul

•. .'

I:
=.'75·

r:
(

,
~.!

'.-

-)i

C)
t
r:

o
\_

r: 0 .._)
1~

r-,

@N

---.

,mt ana£'Ki!Ciolli'O!~. the ~Qhuive !ID$~ :g;:lJ~y wCJre !d.l'!Jlil<l:!"in type 1(1 d~e:MilkyW,*,; Il'h.cl1J.OndetecdOll ha. dl'C: fOC (lilrlt~jl1lg BmJill@j111.tltide (lit :18) ~l1liplif.S arrougb IO:~?WJ:r nmi~ of -.,600' MpCi 011, IiiIfJ di5~8Jlfioo fCI !l]li:l SGlflooe. .~ (:a!ilplaoo all. llipper Ixrund Om dlL'l HI~)G~y dis~uc¢ 00l' dIe 'bUfflt. frol.HOlUDM ~le.a.su»
!lJ.J~!1I~ A!ls!J!~ir~£:
<1:

of the brigll'[~dCroc~io'!l ..~

lr

Itol1!!l~

c;) .......

b~n(t~e;noo'If!~: i~f[l\::~<lil"'dk:

lh.30m~:b1,5in

:!:noom

R~gh.t .u,cEn.s:io:r.\ (J20

a,o)i

lflg. 1. .~.ilI~tiWalli~ielfigfi m~ge ·of thel1eW !il:ir~OUliie']i1gl ttie burst 'ile '!!ira)! ~le ;and (iootaiii~ Ir~spernv'lI~Y t1(1!i\1' lHoi <lnd H ~1E!I'IiIi~ia.lllamciat:ed with ~he SMC 02,. 3:1). frG8se.ll Ilfldlrk the pmitioos Il'f lIeli\i'le kl:!OVifI I~gd;i~1I1ltD~f$ ~n 1h~ SMC ,a1il~1lr~ arliilo,tatedi with their' 11'alm6· o:IliIdOMs in, p.;!~!'I~IiI~~i!'l g Il!.!nl1Sof cm-3 pr::. lih'i! lopen clr,dlE!';S sheJw~1i!: IPOSi]OO:JilS IrJti o,~UII!13 beams inl th@S!!l.!~Y peJinting o,f diilrrnetelrrlequtli.to the hi1llllT·lPOwerWildth.l1Ile :sl:r;ongestt de1emol1 :5dfruralEdlfue ~mgle~bit digitizer:5 imlthe di!~1J~I!li:r;:lmll S'!jm!lli!. ~lfIdi~!'IJg th~t 'its Stflijl :.-... ~~. Its locatnOf1lis m'af~ witI1l .1:1 :!iqllg'iI,(l:!:It !1j;!Jht alS(iffiSilllifl 01!i1 18'1Hi~6~ and deol1I11atiolfl-7S'~ 12' 19'; ~J2I]OOI wOfmnallEsl ll'E! [limer 'll'iW d'eternoos I(WlhSlNls of 14 <lnd :21) "lIFlI1: malrk.edllllli!jjh :lim.. Uer cinles. The: ~rurallcnli mlilkeJl; the true! poo[tmn diffi;ol:.llt to locatlize iiI:ccuraJtely. lh~ pO$iti:r:II:tall!llill(erta~lilty 'isliI:ooninallly' ±?" Qlillhe Ibasffi5:Qflffile Iha~f·po'o!terr WidWi ,o;f 'fiIIIe lTiiillili1l:leam s::Y*m. HoweN.:!,r~theliifuE! rpoft'ionis prijlbal1~y :S!tigfitly (a t'm artIiI1i1!i~ IIfIOtfI:lliwes.I :of this lpe!'lmon" g1lve1i!!the l'Iiondet·edJlmii of tille li'lullSl1~rn o~he~ th~ IIile,am'i.

'*Ion

Iruedhuinh~~Mdl~ all ba.rym~,~ :ibil~y h:mimd. l!~einl~l!3htC'l:lcDMis ,e"",pecl:I;.'d OJ, 16) to seale widl roclSl,'Iii[l,'" .8I$DM - :1200'" Cmt-::5 pe for z .~ 1, Sll'bl~ug d'le c;l'ipoctecll OOOBr.ib'udolll. 1.0, li!Ba~ DM.Di:Olin eur Gai~~~y ... "'~ Illd)~ z = 0.:3, "vl~k:hCQ~~I1!~ to ~.d)~"'!!lJt~~·Qf -lOpe, '!1ds is Wwly OiJ) t!;ppef li!MH,oocln~ a hosi: ~~llMy !l1ll.dk1tc&t e.1~'Viom:nellt oCluld, bod] OOJllribute ~o r itle olmir.red! .DM. Usirng the elec~ron (len~iliy m.oocd for our GaifIXY (.J 0) as: a guicl'c,wc ~ I:1Im~ill d1l"t dlefe i~.:;'1 2:S%pl'6lOObd.~iily thatU.~e: .D:M 'CGI!iJImiIb~~EOO flif(l!llJ'iJ apUIa!~iv~ha<il. g%l!(l[KY L"l > 100 c.lli",3 pc <!11K! henoe Z' <0 .. . Ob'll'io!!!8!Y, jhe 2 Iltore disl:ant iIl'le S01J!'1c:e, 'dIe: nlore powerflillil b~Ol:nes as a (mlelilltitrl oOS1.1'1iolo,g~.~lprobe. he T
so~c ellll1fU,. ~o\l,I~VlU. olf:t'fS: U.tt~e 1:'tOjlC:of a. oofii\ilrl'!,l'~ mlll~VCf ~l lfib.ill: $Iag.~. 1b '~ii1:!1!Jhi]e iIDi:rtile

REPORTS
i~clJi~tiy~c.1i~clJ!l~io!.1c~ .. pQt~m~i<l,l 8Q~~ ~!l!!]1ji'~QSttY<l!~:cW e,Vl;!!]~~~s,w:e~J,'dOiPtlI dhlt.moe orr 500 Mpc.. Th.is:oorresponcis. to ;::- 0.1 :2 and. a

oo~t

ne

Qii",:tyl\VQ c!,!Jrre~t~yk~()\.'!,!~ ~cliiQ

5!0!;!!!(:~

~p<Ji~~,e gf p!'Qd:Ul;i!~g s!J!cb b~'rstsll!re ~w.e ~Q.

lflI~illg radio I~ruruls:icmls (.RRATs),. dlIoqgh.t to !be

I~{)stga~axy IDM of20D cm-1 pc. ]n moogmlil'~Gn orf the oolil£idm:aMe ·ciiL.'>'Iance ~11CCI1:aJ~llty,\ve fiag.~rofii:t!~ Iilili\l :i.L~ D~oo=Dt500il."1~p!:l_ ~ffhi~ ~oillooe l"li.V'~n ~yo:d d~~ l~l g!"Q~P, i[!"iii)1:!I~ rn'ili!lO\dtte' iUie I~m~derl!!litlVie I.mlil' .o:uJ. Inhe~!~i ... »~ co'l"'I'nn de'rlsi.y of the in1it.l.CllIISler medh.!irll, which is 011.1rrol'ltl.ypoorly oolll:slJ-:ainl.'Jdi (17) .. Vlhat is ~~(li ~m~ ·ohhchui"st SOlIroe-?f'ronil 1~lEm oo$trvoo. burlll cr'i!J:r.liI:!on,fiIu,,( dCMit)'., and dishu,!C~. W1,; ~.nil'l1"~; ~IDIL:; brigh~!iI~s It~!.~~ffitill!~

proolloocllb¥iilltmiUllitmnt j:llld5:.'ll1i'S ('iI).iUK!. gfallt ]ltlilses fml1nJ ciitlmr a miMisecoilldlplli~:sa:r Q:,ri1

jl(li)ltfig ~~ergeti()pU1i~.1';A t)'pi.C\I. pu.lg~ fr(HU:li. RR:J\ng{giil~ol (iHd}i:~ d~I~!a'I~ (j!~~ ~1)-6 l(iPC wilihoU!" Q'b~,~ i!j,g S%t!l!i1, E vet! OO~l,eof ililli~ iwigiltest ,gian( iP,ulses Ifro!TII d~e C'r<!lbfl!i!l sat.

"'1~~ly.~ooW~~ ~~~:;Ji~ve~pby~t~Qf ~~i~ i!'!!~!!5!l)' ever 11i~. ~ of <100Ul :5 .~~. ,~~es (:~ie, .. I!S2.5Q of,'Iheclltim sky) lIlt any given tlnle ov:er a. 20-day poo.oo.. A'>sfh1fa1ing the btlll'Sls to be disltribhltooiso_picaUy .;a:vc:rdle sky, \V(l ~I~fe.ii 0., lliC!l'iili,~al GU~ (If &2c5W20.~ 400 .silli!iUli!I:F '~~iil~
dii¥. (,liiv.el~ourQ~~~ijl~§J.SySfl.'tln~r:ailll..'" lets; \7I'e e.s!mlat!l Il~ ;,'I. W -Jy~tho b!.!rnl "'!,!'{J:l.d~ d~ll11lMe ('Il~l'0 :;:- 0.3, ·01II d~natnce be

per

!.1.d ~lCn..""f!T(!]ca .. 00 ~ . ..:...[ OH{D:1ioo/fJ'~)~ K and -:IOfiWsD:liOO2 111.!'eSl;)octiv;u~J: 11Ii!ese values, and Hgh~l:mveI4intc a_~lm1tIllslllQ( 'Iim~(IJ}e SOl]roc siZil: ·~<I SOO'lm tb:li'8JI!1{III1'C,lallViis.tLe ~~, imply ~ oo:btlroiM I.lIlilIisl>iQ:mp:~!rom. a e(lln~c( I~OOI.Re~ati.vi~c OOIm@S \v1n1~, ItIlIilk veiocit'l' ,am ~~()Jby!l fa.;l(I' ~r~ith~!'r {fora ~W_y jct.",~n (ljif cr~ I(forM i!nfU;!lUsUv,e ~~a5lmooeijiw!tDere the 't2 and e is the Lorenl7. fac~Qr r .., - hI::! 1[1
a.~.

oo

speed ofligll:n.

!c1r

of! Gpc.ne (lO:mii\'iSpm~dJin~lMlrllO\lo~i~1 i~ ( fnr blUfSJs oflhis encilJ1 is tlIlerefore -.90 &8:1'-1 Gpc-~. A~.IiIIIo;iJ;f,\hooasicier.ably iJiIHX!rta.~n~th.is I. s S(l[ii'.l~wl'l!;,lthi£h.~r dl<ill tilL'! C(ii~p(mdi!t,s. ~Ii~ ,gf01ili!ef .&~pl\Ys~~~ wU!'Ces,!l~(:;h ;~"l tributi(ili!!-'5 ~:t!!l~ee!~ews.ie!'O. llM~ ~rer!s:d~ of of bi!~<lf)' 'G!e~tro!l star [ru;ptrnlls [~3 d<1iY 'Glx;-3 -], thlsbWl>~ wl~icll i.s SOiltl!~;two o!'d!cwso r magnitude a.bo\l'eo,",r detect'um~ UliresliH,ld. ~~~"1I1d (1'9)] -ilnd g.a;I~llW<Ji."my m)urn.4s[~4 day:-~' (:;1)(,-1 ha!,l·(;:casH, icdlo m~lly 'C'l,:'CiI~I~S allowcl' [pIJllse (2,O'j],lltED. wen ~1Q\l,!' 'dill rntc! of C(lro<oJ]iSip~ sll['Cmov~ [-lOOQdla!y -I Gpc -J. {1JnA~(h{lI]~]~ ,mtcrg~.eii,.c'i~ffil!!;lr:ha. th,c m:ig:im'lal ;~II!I:r\l',ey&t!l IirlGlia:l'ili1P~:icCl :iii:com.,al~bill'l wid~ gan:u.11iI9~r:!I:y ml@ or foi!tO'w-l'IP olbsoilrvatiom:. Henee, it 3PtPG9rl> bli.lrsI1'l, th~ bttCiShtl[l~~g W!t~pernh!!!'l3: ~CI Im<ld[ig Il) ~pr~se!1'~ an 'L;\lllli~ly !l¢"t\\" cl~or ~ad!Q ~!U!,ce. freq,l!cJl'cy 'We: !Clb..~!ffl0i far Uti.,\: b!!.!nlt .are MgJlJef WlD.bpe9k lUllli.I,1'Q:sities oif 4 tlIy kp:r (i8), would 00 observahle CUI 'tOo -.100 kpe wIdl Illlile !>ll.ili'ilill S.y5l12'1!tl. 1I~ adIlition.ool~. dle RRAT OOl1li:l'li ~ild:!:[iU'l!t p~~s~ forl(n ... pCi\''if(:;r law di.~· ...
TOe8!~!1l<!lc e mll;l oJ shlm~lar C\lCU)S in ~lI!e than cme!lU~' diiiscussedmec]!;li111sl'I!!S {II' ~~rll~~~ :fl'ldio s:ky,!A~e mGt!!! daaJl [J~,c! mlVley we ~a",e timns l'rnr the obsrn'V:ill1oU OfpfOlll1IJ~. rn.dl~Q; cm~~

sij,om from dle!l:C .oouro(!Si (12).. ~I~s; of Itlm IPil),!lical ori.gLtI of ilhis. Inlrst, we:~rodi'Clihat Ii:lXlslnng data from aliter r!!!I,~ $!1!!'¥~)'8 \wilm IH~ f1!!do;~ n1ylln;J(~a:vn syslen~ (2J-.2!~' :should oonbi!~ ~ever.!~ ~t!t!n~r bm~l.s. 'i]'I~'err d'i&iovel)' l!,liQulld lJOOiI1U a :1'11O:I'e: rcli:!lb.l~ es.tm~B.~cof dl{; ovcmlll. 0VOOl mtc. The:
'Orl.

firraiy odler .li'uIML'lJ:l(xl :wrvcy §0Ji rncl!io.Iral'llllimus d~is HI.l!IC :scalt:l (27) did norhave $I!llfici(')]ll ~ns.ilivity~o d~~1 ~niIfil~r,~~li1L'" dt¢ mlt~ p:ueal dieted ~iJe:Ee" l(l<wer f~lIertcies .Am {-400'MHi) wl~CreHHI~}1 [)ti~J: SlJ!r'I'oCYS; were ooDid)l!!cled. alntolil£hd'lC sleep SJXlclralhIKll:e);, ofdlle S01lLr:ce

i!liup:tics 8111 evcnkigh.er

scattcr.ing

nux d(mSil~. the prediclOO.

bursrs

~im£ (...2 :50) wofID1.d makielhe

diffiO-i!I~lo d~r:ecto"'Ll:O ~~e:rndiome~r noisc~ At t r~,YC1'J!(::i¢s near 100 MH~.;,."I.1o'h~ ~.(!!lN.,r~q;I)I~ncy mazy'S cUliWCnfly Ulld.'er lQo!~l.!:UCtkm \~'iUo~c: (18). the p~dlkood ~~~gtbne 'wo!lldd be om d~e ofderohCV1€l1al man~tes;~n(l :hcn.oewmn'ld 00
IJindd~I(') .. .p·~mb 1El!p5, IIllil~ 1:n.oSl tntrig.lllilll g fOOUlm Qif :th~s bUfl):l:isi'l$ .30....ty surol'ligih~ AILhfflllgb. !!Irlns has

100 IFig.

:=lOll'

~O[l,

Tim.!! iif.le:rm'

:19:511:01.63, (ws)

;2. Fr!~Q;L!lem:y E!'\l\Dluilien alild iRm'QF.lmdl P.1JI1:51El lltJlIPEl Ielf~h'e r.aJdlio Ibulrst llh'ElSiilll¥IElY diarta,. :5 ,c~II~(md 24 Augl!l~ ~OI]I1. !HI~ shownl h~rn;aIS,i:! tw,o"~nUlill';l~sh:HiI,!l!l"'wat~fuU ptot" ef '~l1tINlS~ty!:l'S QUI ·aJ flillllil:t:i~rl ~f rod~lo fr'equenc1f Vfil:5 l.!:S tillite. Thed'i~l!Ili!:l'5noD1i;s; dearly seenl a5. 'lI,ql!l:a:d~atk ,sweep aorQS~ ~1tI'!il rrequrElncv bl1llrldl, with hro.a:dlffilmg mwarrd l·owerhequell!l(ies", IFroClflfl.Ci IlHN3ISUH\1!III Dlto;f~h'!il p:L!lLse e de1iaiY ;aJ~flc!~(I 'the recei'l!ler ila'lil.d\, we II!ISledi:s.tafldi3irrl p~l!s.alr timinlg '~e(hI!1l1~.lJe!iamdl detenTi!~IiI'OO ·tlil;e D.M to Ibe :3175, ::ii: 1 (:mt"']' 1Pi:. The mcii\imti! llilles separME!dllDy 15m!; that. bcliilllidtJ1le: p~L~!! showfhi!
l

1~~lperted lineh8lvlOili'flOr ·thE! co!ld'·,pl[lsliI'IlCIl oos.perSlDni 1~[I!i\lal~umirn ilia DIM lof 3:]5' 'bm-~ I~C..Tine liu)I'i1,20illbl tilil,e ,i3it ~i.3l1 'GH:lli$ ;QJ1i!1 ,a~tl~a!d'iililth~ d~taJ !Call,dsed !i)y ,:;I Iillilltfl,ll!!dil)nilil{llhql.Ueli!(.)' ,hililllrle:L ih~iS. !)tot: is; fO!r Olll@ O!fthii! O'ffS€t b@aJm~~lrl wiIiIh:h the' di!li:lii~rs W~1l! fillt :s;atuw.arl:@d. By ~p!~itting the dlalta 111100mlllu h!il(l!llelllc.y slll~barnli~. we !Jave Il!IIIeal!iunl,d bG~h ~~e .hill~f·!Iil(lwerpulse width f giRd nux dfl iIIsity ~'P(I;arl.!!wn 'O'll~rlh,~ olbsll!f!lJiflg IballildWi:dth, rAiOC~'l!Jnltili!!li f~~ IiIldls~ Ibl'l)gdelil'il1i!Jdiy'~b:I Iknowlll!il'l~oomenrt.i.d~flie.cts, we detErlli1ll~Ifl'E!a~req,llIemy $callllil!ij rel~ati1i(1ri1,$Mp, for the Ol~iSiml',ed Width 1W= 4.16, ms VI.li,..4 'GH.z)I-4,8 ':I: 1M, where:! ill the :ob5lermngl iI'\Ife;qlUen~y•. A. PGlillel~'~i3iW ffiitm the Il!IIIean : :~III!f):: d'elilsi6ie$ob'taiined iIll.!fIadl SJUilband yi,cld:~iii spectr,a:~ in!dex ,@f _it· :it;.l. 1ihe in,set ~ifiI(ilws·ti,e tata~· I~OiNer :Si.'Qnral. af:tE!'r aJ di!lpefS'iv.e elililj G)clIrremOl'iili:55UiIi1ll~Ifi'ga 10M ,of 375 '1l1i1ll""lP!!:: il1di illI ~fei~nce rmeqju:mcY of 1.5:il65GHz. llh'i!! 'Iliirnlll a)ii~onl thE1!in!!le\rfri~ure <llso sp.1msth!1! range illl tel 5mli 1iI1iS~.

.. UOW~l(I_~ ~\iI' COllV!!.l:CUnJ,g ~ero. iI-.. e:li:.tfalc~ri.ll1 1J!!llu.!:e, ~~e :flllCt 'iI:!al [I: is i!TI(I'~'e; thi'l.!] 1.00 tinle5 OlJ!!f dclltllC'liom t'br·esI1iO~(I g~l!ilkes Us Il!!lildq11lel~essHmil.:iarlg. ORen, .aslrO:llomriclll. I S.OO~C5 E~I!I.'I!'~ a UW(, d.is:u-iblIlioll thill woo:~d llatl.I]'3].!Y~L:lfld to 1ll:!!"Y burst ,d:C~oct~ol'l.~ of lo:wet (lli.gn:il~lCal1l00.; :tru.ch !Z'v'(l:lfI:u;are nat oib5!~NOO irl QUIit' d{J!tll, ~f, Q.~ HK:Q'th~li !~:!~d, r~hl\'; b!l!!:S~ was <l. ro~ ,slarnd<lN Cil!~dle.,.nllo:re drn:!<ll!!ll SlQ(IIUQcswOlIki have suC<1llI.q.e OMs th,il:~ i~ihey wOflld be both mcl:~s:bmed toiGw~rmd.io froq ulmd~ all'l.GO'I!II5·icie our~~i.t,'mpmd.d!~sper.. sion trials. :~fr,tl'(t ..11nft.~.l)f Iffil{:lr :host g8ik:udes ,ame m,~IDf!!llflblJG, tl~l'l{]ttlIHi3l (lm'!l p{l!pl,llati(il:I~ I;JiF rOldio iJW!s.ts:al, co5~lologi~~ disJilnce.s!o probe the iOllizlld hllll!3fg<l'l!)ct~cnleditull1 (29) is very e:Ncilil1g" es.pedally guv.cn 1~lbeCOI1!>tmcu'on of wirnu",flcM.in.!>I.ru.i'i'ii.cnL'> (.NJ1ii'l :pre~aF.:Ukm fl:I!f tltD Sq Ua!i'EK~~OillliJ~li'C Army (3./).

_r;: ..

779'

REPORTS
REfi!~e:n:lOE!sa!'!d N'OtES
LalI;i!),U, A. ~~~nij!I, N, Mflm'. JiI~. 4S;. !I.AS9/(~(I'04). 2:. B•. r!.L s, Hl~ ~ii'i, Nt 1.)iii~Ioo\I, MMUM" til. Mti'oo. 5M"
!C!!tde5,

t.:~. . M

r,~I.;'11. 1

lB. ]1.1Mi.. tir~t NI. 0. R. l!llIlft, iI..HI. H.!IfI~m, ,M., A.l~f!J!i~liLllf" C JI. t;il:11l(, Mr~ J. 6Ii'.,m, 12004). 1:9. V. Ka~ra ,ef 1('j'."AJlroph,:s.. 1.6GliL. llW (20014). 20. 0. (jj;Jetta" !Ill. Oell.il Ma-~~ J. 657.

s. f!;.

~" rll..lli:!!E!!l. ~,t,= ~~6, .l~i~('197 ~. M_ t,t Md.llrugli1ln ,Llr'tlL NQJ~ 4~'9, &17 1201l\S).
~.

:3i:ilZ, 9~ (200:Jl 6

n.

(OOfn). 21. 1'. l~d~1I,Ill, II)·ell.:i V~ll~,~" l':~iiIii.gla. MM. ~i!.

vane:.

us

3,;1•. 5:.. ~ramJlmmrO""I{. L St.liI;'M:.j!y~Sfi~tlil\ ll..Mo. ['jJf~, I'Ll. Sitlil~, S. L SlKl'IltdlNl, n11lJ'i1. NoI. lit ,.tr/oIlM. ~r:t<. ;~Ol!. o!:li ~U~W.

~.~•. flrie f;;!~e~ RJdli0 Tel.e~I!r;rei5 IP'l't '!lIf !h.e J!w5;lfa~;<I'

s.

M;a1"dl,~i~@r,G. ilrl. l\. G. ~~. F

F. (J~l'i'rl:irdl. JI5j~). 649', BS &. L. :St"w!l:'e)"~!I!!iljh 9' af .• AN;j'"AsJ~

~]OO"i,
$0(;.

\1'.. Mi.. K.a~pi, Patr. 13:, 2;43

Iii. A. ffl~~~I~~. iW~~ ]. 5I!.l\li, ~Ml ~lli.D}). {Ii" i!t 11:. liltilifi!!r, ,Nt ~t~mt!j,~MID!OO1 fl/ ~ Mtf~my (C!mI!!Fr~ UIIW,. ~1~.iS.,(!nilll'l!!g@. ,2()Q,S). 9. L C. ~!ll~, ,~ R.I~~p~, MfI)~. J i~O!!l,mi,
~ll9'761 10. ], III. '(aMi,. T.~. IN" LilifiD,IilU~l:It'iI:xiv.JC'il~~~~~f!)"RI!I.

r. .~. . '(!!~5, M

IU'Mt

M1l"~~. 51X. Z'91', LI!.7 (W~). 2~. 11 P. MooqUi!lnl~M~ffl'3'> .· . I" 6<58., Ili (~!il()7). :n.. It N. M~rndl!mu !1t ~ •• nlM ,NDI. ~. A!!lItM. S~ ... n~, 117'~2:00ll). :M. II. T. S~~~ M. IBaili:5i. W. V~II :Str,at'en, ,M. C. BrU'~DI~

M~ .. NOt. R; l!.IJI'Oi1.,so(. 32)6, 3'~a 12:00]1 2~. ~,B~r9i!~ e~ i'!I" ~~. NfA. :ft, i!l.!!\r~, 5«, 3'68"~a:3 j. i'i§o£i. 400, (20ill'fl :21. :5. W. hrn1. 111. II. l<I~'. A. ~.lI~lJgIiUll!, fJ'(D(" Awoo. S'~ hliit.a, lil US!8'9)' 2B. I!. \V. 5Ii~ppllr:5; A. G. ]" 'WIll L.eel1J:\l!l1ii1\, M. Kr,3!I1J~r" I). S.nrneib:!1ing. l. He~~~ ill ~,wi1Jg't aJ flilf 3,~:J.
!l'kRii~ SwJi;ltl~
,!Wi ~.[I/f!)rj

(W06l. 36 •. ~. 1\. ]aomlJ)l;.M. IfIlt!!lrn, ~~:ji.!l

Bai,If!l:,

s, ,rll. 10l!l, IH.5,

toIi~lll

/I, W.

T~~!:S~l1Iptl. ~~!ill~ ~~ 11l!!1I~ ~y ~11!e Oi:img!'IWe;I~~!l! !\1ll$1Jf~Ha r~r o",21,iI1;[;lll:i,a~a ~ilfti~Mt fae~i!~ !n.;;IiI.l{jeodl ~y me' (1ifrn~~11mJ $rI~mllil'i~o!I'Um IrntliJrtlial ~~S!lal'(jh orgaiirl!l'ltkl:lL \jj,e<. '[tHIrd: ,~. Marndl!!!oI.'eif 'for If.I~Mi'i!J! thi!! Ilrd~Ml d:liA .i!vAlla!bl~ to, I!l!;. TliI~ r.t!~ar.dl hlu ma!!lli! ~!~ (If ,[jam ,DlJ.1iijlil!li!l fr,am the Higll llifl@1'W Astropl~i(Ji :~,et1I~ Arl::llivli' ReSl1~r(h (;eluL~r, !IflI!oidfdi I!rol N\I\SA.'5 'G'Jdtl~rd SiP<!'.i~!iliiilJhl, '(~tllr. W,~I;b;!(\Ik K. IijUII~ fer p.:~~1!'!!l <l~~, '~~. \e GW r1-e.~Q!1o; .;r!"dli¥~, ,~!1!i H 1/. !Wt!dr~ill ...5. ViiliiPY, S, Jiiflll!~gfl. ~. (a1l11~~, .~ ~ , ), IBl!and\·IiiIa~lttmFn 'trnr m~r..ll oo:mFlt~ilB ,mil ilit!' flilllrlll9!:flpJt W!I!' ."ii(&rIm.~I~1ig1!!lU! pnlmpt. oIl~Vlird1ii!ii of [ follli.W-!!I1Ptlm:~' 1:r\I' tJl! JiTNF [){r!I!d.lQIf !n,d 1l\\\l L. !!M!nlif!V ,md P. Sulli'iilm' lQr ~b>eMllgl,m;MIIf1(~"

~r

O~~1~6 ~200!2.J,
U." ~ .. W.. Iilil!tlill!ill, II. ~. H~'rtm. T.

J. IH2Ir~:!.,

41'01;)'.Mf'J.t. ~

.Mtron •. SG.:i~".3il11 GOIlI~., l!.2:. It H 1If11.!!.~ ,~r' ., Mi\r~~. J ~!lpp! '5eJ. 1!l0'l" :l!2~ m
(2:006),

W., ~e(jktr. 111, iii. ""~r!!!J,

l'fr;J~!~f, (i~1l!1'Ii!

B. I!::" HIUI!!)", jitlF!iOil'al (jJ~lUllloollfilllml. 14. G , ~tuT,el a I'll .• IillD1:;tn .. k:.fMphy& 4.:iIl. 4'~ (IDOB:). .. as, K, 100:<1" A~rophJl'. J;~!l:, l7'9 t2,O(lJ)' ]j" So 111!1l1l:~,MM, UfJt. R. AQ'uln. S~~.~4.8i,99'9 (2:004t ll". ~> 1t.1~l(r'~)i.~. !ll<ln-ge!;la!'!,!I1!~!i, ~R1phft. J. 5;!,)!,. LlU

~9. \1'. !.. Gilil!l:biH~,11lfljlm! :!o. :5, ~lolfllfl!tl)FI eI d" IjrN!-' SM iW1!irIr.O .13 (.l\JJ!~f.a'I~
1i~f~Jl'!! N.llt1~m!al. f;~dtlt,., :20(1). ~1. P. N. W1lmlNlfl, K. ~ ~IL~frmIiUl. ft. o.Elblr~

"Y, .~QOQ),

~i. PilI

Stl!l~ ~ P~fi<l!$, (r~~5i~.nru.rWIm\8~i!!

slIp'pc!mn91 OIll'~ilH!.Ma!tilrial.
.'1'I"jlili\:!,ifil!no!ei!il!lgJ.~

MII~1(IJ. 2;0\1:6,~1'5 ~~9il3J.

[(jiuilrt:onlil'l~ll!hIlV.liM"lS:jl2\lIOC~, fl.tatffi.als <111m lI'lttllOtH Iligli. 5:i <lod S.'

R<~f~relflt!i~,

tll9'Wi

li. M. CoI11l~ 91wLy 200[,1; ,3m\pleil Z05El!Miell1beI roO? Rfy.ot:9, us].. (21004). !l1il'~i5i1ed 'L\llIi~~ 27 :5~p!e!'llber ,(1101; 3~. II. IE.G'!!,!$!~" !1'. It. #,I'jt.C!!ltg~!'gll,~. ~ill!(l. 1)1. V!i~ B1.!fo!l!1l, lIO.U:2Mtie!!i!eH4lS·n CfldiJiIi! Iillillml"~~maMn !!,onerncitiiJJjlllli~ pa,pE'l'. fifo!J(. JI!!.IlQ.il" .soc.Pli~. 113, n:t!,~UD~n .. 1'.1. W.
ILiI~:iI!.\ N.. ,{[mm.

Nan,OtSCII!le! IF'ri,ctiioln 'VSIII'ied b·y

Ils,olOIPic Shiifling 0'1 Surfalce Vlibrat:iio:na I Freql,uenlcies

Ammt~c

de,pem'fell~ 01il. Ihe aCi.so:rnales' Illlml!ll"aJ viil>mliO:Dl. rroq,lI.lGmCtCS (Fig. :~ Bec.mJlsc lfllllt~r ).. alOl1lS v.ibrntefus~icr; eucl;gy d:issip8!Dioo :shOllilld. be more liap:~d., aud di'II.,Yefo!rofi:i01Jro,n !li~"oo~d be ~Mte:f than fricl~:km pmdluo~d by l~eavicr S.~(::Ie.s" TIre $~n~j ]rn;)..~lik'elylo exhibil o])!;~f'V~liie

IU I.IItes

mMS[lQ11mlS!iU'I;lhydliO£,!iin

CHl ... 1l1~cl:d~l.Utcri.~

limn ,(DH~Uinimllcd Sl.Iifflce5;. Illile m.O:Si d,l!Wailllle BlIldii;m~rt of WhL'Ch IsdlillJ'bilom:l. (T}.. H~ and n~ Fric:tio:1iI,WIiI,vem ki nellj,c Imer'9Y at s~.dililg ililterr~ilu~sil'lro taffioe Vibr a 'ttiOM" ~LUit the det .. ffiiloo lriIiIElChlilnii:smsorthis p:ro.(f'5'5, Il'Iem.:lJin unrrel>'Cllved. ~mlCe' m:icm'llmp1 mfli!lSI!l~elil'l:enrt5, we-mi!l'~tha~ ,chaJnlgililg1!~e mass ,oftlhe termlilril[lijlil'ga1o!:Dms om a sumfillcie, ",mi:! 1!~mlstheir vi bralional freqlllen:cie's", aiff~m !:tg'!iI!)s~al~~rri(tllO!il :uibs,t]rutii~l1y,W~~o!ililpa:~d litydrlOg~!iI~~,uadl s d~merhjm"iOOr'~ll1!,~td sffililgb!~(~sta~ dia'~(I!ldlail!idl :s~[ioon,$l!!.l:fac€$.!l!l'!diln all cases .~~~ hl{dJ,o!lienat~d SYf~C~ Ii)i~h'itrlli~d l~lgllil,@frimollfl. Tlhis llesui~t!mlPlies ~~at the lower flaWlf.ii l,freCll!I!!IU!(lI of mmlS10fbed deweriulntI f Iredlu:oo~~iUl Irate at wh~l;;hlthetJi,',~ IiiJlletii\:; Illnelfgy 1:5di~5;iIP redl,,"I'rn:5; di.sw'II',el)l' is mlH.i~~liIt with II .. lrililodel del!(rib~:ngl IlII1lllrrgy ~rilnl~f·errrl:(Iarl5nrba1ies, from a mOiving ~l1Irr[1{;ll.

lui'min~~oo srlUcall (:Si)1 sunaae;s .. less stabile (Il~.(l.Sl,II'racc: Qxidilz,~ ~Il 11k .aJlfur ~, ocl;hourn) (8)j~l,]~ swd0n1g: Sii p:!~:j,,,~d~~am .add:~I~ion;;)Jrest <lnd IlliOvicle!l irlrb:~l",,!iL1l] (ill] 1Il!l. hIil;podallt' n'W,-

a ~~.moo:ciled~,~Ii~ .<Jilbng ·Oil. MlIrf~ejbutk5'ed dltsslpi}~irnl. OOWf!: ~!f ~;he gr., '. m. Vi~~ ..Jimml,I."le._>~ y; :Ii~ll. oe",.ru~b~~.,.,g on lID!~riesof<JI'omlc .•. .•... _ ~.'I'ro bodI~es ~:osclll~' IlI;Qch.:!.C'es heal. Tins . lip"s trnUlsl~IIOl~ai~'CIlergy c.m Ilx: 'CClU¥Cllted lo ~:l"C!Oess OCCililI"S, eYen :UIilth,~ IIDSCIlQC G~ ~M. ~u, la/Idee \",tbmli,0l:1S or c~.oo'l:li\l,dc ,aam.cl'S (1-4). I'~; COlJlalJ-t.·mOOealDmlio. fo~rni\looSii)opy fAfM1I wO:lI1d belOOllnol\og1-ca.U.y oone:ficial to <lD:l'lOO~. haw- en.ergy .i.\l los'i. 'd~roIII.f!'he;l~!I. of thooc chanri'C'ti:OU COl'lve~ ~1OlIl'l-~~iM!~ot.li!l~. k:iR~llc !;l!W[.... 10E\partnt~liI! ~& Ph~,r;S" UrniYl!r~tlf

1'1'1

'Wiil{OCli~rlFM.a:dioolll, M~dii50~.W~51106, USA. ~lD'I!p~rt!J!ent ~d E~ine~ring r~fc~,. UI~i~ersrt'l" '01 M~ooi'!~!1-M~(!!!~, M~~~~, Wii 53:1(16. U5A ~Oep~r.'l!'IlIln~ i)Jf (hE!!:n~strli. 1I1!1~~~aty oj
(I!~

n.elJl byllllii'ling .pltu::tll.ont<: ar ,~I~lmllicpmpem~.

~~f!tl)'. P<trk el aLh~c~5e:d ,n;i'!!iI~!,e friction ,eJ~"Cir(ln!c.a:Uy (S)I~iVhe1Na5 .~. i~he P~!ilA~ work
~

H~Il~!oo,

HOIlSlDt'1\; 'IDI 7'1004" U5Jl

"PIr@s@l'Il ",rIlllIr\l!':!~:: ~BM I!iJ~.l!lNIrdJ oGrmti)H, Zuridil

I.<lDIlJ.ltl)"f),.B80J

1l.@s!!iIioolii

RrB~hii kom.)~IZl!!tl~md.
li>epOIrtrment

bm~:OlJI~1 ~~m'~ of oor&cics. We: a~m~ .surflliCeS 'by vruyiJlilg !iIlGma.om,

silo'w rLlnd,fci:ctr-on ililoo, d~rg&

onillil,e v,i~
~tr~

°fP.reS!!l!itl'lddre~~: HllD4, I!.ISJI.

IEhg1neer:ili!~ UfI!!.w:'r::lityot f1::'MiS~'!la;_~ia.mil.adelph~iI.PA *Pre~~ idll~eii;: Cenlifll '!o;r ~r1o~le MMef1iall, /I.!fg~F!e WJ~tiQn~1 .;!tw~tQ~tJi,~gllfl!1![!:. I~ ~04~:9, 11JS,i!L, L
§Pl'~~l~dililf~
,md: Awlii!ld IO!p;!Iit~el:rt m-f IAecl'lOlI!ll't:l1 Eri;g1nol!~llil'ig MKhani(S. :llIl'1il;'El1!ity a! P~Il!'i~M\a1lliil,. P,ITiiI.a~i!ll·

of Materi.aB .Science' a mil

no!. 'DImc1,lrunl.!l,Ify, of IhL':el~emi.'>Orfu~d if\I111l.n'lflfin;g g~rfacl:l atom, .iLeavtrng d~~ gll!tr~, d~~mn1lilry i.n~d~<I!!£1>daVolid:~: che!I~~1 ,e'oed!!'> due kl

'D s.tretch
FigJ. '1. It SChi€!!iIlgjt]COlf thli€!' hkti'()i'I'~li'flittJefface'. Vllibr.adnglilla ~tlrWt.e:s, curnMe with, ilIlntl dliSiSm~\are Idliletic; nel[g~ fmmtItAe mlo¥fingl tip ,at i!I rarl:e tha~ depern.dls olilthead$'orba:te":s fiI'E,~uenICY and
,ilI[d]ft,~rellflt;

dilT~re!ilinter.facia~follCeS.&se.d
ofp.l~QnQuio d~~paIDionfior faao. mfmol.aYGt' 8.cts: as
il.'IC:djrl!iit1.

OR

a :~mde~

;fricD.io:~(6),. l!IiIe SW'"

an tYlCi:'gj1.iI'fllLn!>r"e.' fmiill dli'iUp

phia" PI\. 1'9'104, U5A.

a.Mlribli\gk,iit'l~nietl:ne:~y

Uii!l.s~1ts, maJsfi;iI:I1ati5, than for D.

liart~ fC:if H

REPORTS
9115~ed. 'CQf'. devices !I1,!l.d~j'fiW:~l~. H~ ~irnsl~ ~a!.(; .. t 2'160 Ql~-l\~j! ~~.mtJl,a~oo ,~i<l!ll~Hld! ~~Q 'e1'd~,ib~!:sdistlflctlv>e ~n\lin:Jll ~Q!!l,e C-D' s~ch, Analy,sis gf ~e ei,ec:twI1l1C proPl:u1:ies IDih,s.t di::pem,cil on the eH reg[(i!nfi:mll 2750103150' CIll-1 sllO\:ved I~O orn:l.cm~1r3tion of sW'moo pl:tysioolriJ,eo. OOI~II!.Ill~ fl.l3jJhlJ:eS ~\iflC3l1illy above ~heb3c~clI, dflll1,. ol:lsu':t'l;ling ['lin GOVUI<'Ig.€: D amd 1l.1acl:. of 0([1), by ii!l~lill;s. As dcseribedin the Suppot;nflhrtgoilDlimu::
1~~fhd!bl!f!~1]9SC!:l!~~

of"'adillesL:on td valillles, jspro,po:u:II:iQnll'~ to '1;" Il'On'l1la:Uzoo, by the approp:ri8J~£:pGwet olfOm

dfii~ttC

Ffg~nnh~ CQ!~~'iw!!i!JY!~I!~mlh~J~~S: il:5.~.r~ gXf Mote4 ~rr~cijve ~eolf· s;tre<~g~. (It)m~~''Ofk-

rnlM~~al (9)\ Ihe~bSt:!rpt:l{iII~f iil1filIbjLt~Uhydrno ¢~qCbGm~ d~~iliJd¢~d ch~ngg frictl'OJifOF di;i!~]ood. lIi1ie\'l'b!<)~iOliai~ fwqlUet!cy '00 o:f an .:tds!Olmecl a:ll:U1i1s ~ll1nn:Lned. by'ilSmass, i lll'lJlIW!lSSo.l'll'lie subslrnlJe Illnm{S<}1 ·10WI~Lchilisbol1(OOd. aM. the

Il'i!n'iillla:~iOi'l.01' lil.Sidwl

ltat~
~i5ruljJC

OQj~mct. 1l10011:t1lS {9,.2:6, .27). 'w:hjd~ dimi,. aIIl)' cl~~lld~neGOin dIe lill!lknor\lvn hut

n~rric~g!'l iblfC(i F f ~ ~i.lJfliI O!~d!~· . u~cill as.if! rlll!!t<:lW!f!of 1000lu!l bDdl a-'Y i!'!ioogen .il.lIiI !!!l4tt.;iJ1ighvawurtl (U.HV), <!IOOf!!.tti~g!ldliple fin~ ootwoo~ lh~ H- Ilnd.[)·ti(liljnina~oo S~U:l'lIfIC!l ii~ caalll ~Dc SiOO:lte hyd~". (HC}-oo:al!cd
~p wasu.J'lfid fUr !~ffi1C;ll~ e:(!E'CiI!il1n(\lill:s,n~ fri,c· li'Cj:n "'~mlS ~.o~ @ta ,'V~II;fill I!oa cO!illil~tll!lnl1L

~Ia'.l!ic p:U(l!I~rties 5hea!'~!1gU)S ('To) '\\'ll!!ie

A~llIre a lso es~!~aood! by !!eI~liJ,grea.OOf:W:lhl v.ilue:s: f« Ole dasll!:: coastSirilS ef th£ti«~, (0), IbtU dtC; ei'ective ~~ear

·()f Ih~bP.

H· <.1I:id D4~mli'1~ ~::'I!E~. nf!~"S'Y1t!'l .~Sm1Ul~ari:l!ed i.!m Tl,lble ~ R~II).• !llOOel for dIe Co!lItacl .<l;F~. A ysing th.e !ll00e~ fur ~~e ~w'O IremllrnatiQ~ of i!lferflidai 'fri.O!k~!~ f'" 1'.,4, whe:re To is ~~~e rese!r!aJtl~ f~O'Is·(If P and envirol1I'WlIllnls siIUd!&ed are s'ILoW\!Jlin :p~, 21!3:. inl!!ifFZlCi a!l shear ®'IreIlSi~h. (1 n mood !l1"Pl"(l" 111esc dma ~IHction, mcasurel1lCllil:!I div.idoo. by pri3'Deil~ !I.h,c albsenccof wmwamCll for loadClOm:p81 rod to D (mi)) is 'ffi!dImDI .~ VjIj·D!JJ·11 ... IitIC;ir fL\'JecttVl~ 'OOltWlC'1 ~ filS at eaeh load, iln.de;p0U1.d.cm. sh.e.'lI' SU:'lllilgLhs. We; flldle f:riclioll L.363 (10., 1J). Om, 8](111), ~hc: ralni.ois] .389 dala.wil.ll. a I)QJ!llblll!lUm I1l:LlCh;mics, 11lOclIe!1 deIli'Idirurnil'llg 'film d:lff~ll@ncr: betwoon C-H !lnd C-D (12-14)., S(;r:i~iIilgihe .d.~pt;:n.doooo ·ofA Qnload,. a.8SlIaninlll ~!O:[id I)()·res.tdua~ Dt.'Vialio~ at ~(fwl~~ .m~ :~ ~pheriC01!~, ~astic, OOIt~'\,re C(U1UlO[ (21', 23), e filiti"~ crmrsilllrht:;jc 1_0 t[~e ~l!l<l:U, ~pil,Y' .lDiarl:1ond(OOI)' su~glCl-CFY8~~t Sl!fr<l!Ce~ were l!ct!Hl!U];]OO wi~h H or D mO!~{llayer:ll by means n~is:Iftlidcl cliIMl'n1llle.o;: [he: li!oo(JIDo~!l!lke <!u;1 Ch<l1gin8 'OO!'!I<l1;t~~ llre: ~Ieat!'· ~~~. {eff.e~ (i!,f a. :hot:.flllil:m:cm pmooSSi (:9).,T~~is pro eedure t~vc: allCll abS!J!~me) wcrea11l~mgJ~ of 1.2.6 ±: 0.05 8.SSI111llptDOll5 aboulI~hc ~miSiI extem ofadh,eslou for:~mo. wd~..;oirlerodl. ~!early S3llumlioo :mrfl'loes, erjhe oo191iGnbcl,~~I~ pl!d~r'Of['foliCCS nd the and] .26 ± !H}7 Hmes gmlll:}, frn: IiIm H'lenntllmed as denlo.;ttStt2tooLby !linn fmql1lelil:cygmmrat.1on !rMfaccs for _N~ and.rnv~ rospccli.vdy. wenk of adhesion. S.iing1~~. Si{U~) stilirnlll(1l!l \!,!i~i'iIll termi(SFG) spNlilmiSC1QP:Y (:F~g. 2A) .. Vml:III:~ltic!l.~a~:3;!lCall1lt.tcnrushmlll~ ·be. used 'WIICII applyiifllg con· si~!,!~]1~!~!,> ~ madl~ on tIl~'eb~~$ (lrP1l~~ro>d w 'hl]!!!~ln ~~01!nic.1: to ~1Ii"(I.,'l~~ooHlaclS •. ;;i.<; i,,· !~d by H or D by ~~~ of.m ~tl~l~~l~ (f)~ IU~C qu..[i~y ,[):f'wllilich..~ v.<lihl!l\-s(l~19). FIlIH .oo,VI:lr.l!-Wlon:j ~silQhievoo, dnted by moon !~~C;1I~~ dYIl@JruCS !'!lirlll:Ji!>l.liolll!i" w,c1! elr;;h~; vmffoo by oo~t angle snd )!.~rn,y [)1'l<!Ulelccl~ baseden tl!elXls'i~~m~ IIndilltens;,ily oflh.c e·A (24. 2..n\iVbatev:croo'!'!'OCtimfis were!le"qll!imdl, strc~chill,gpG'ruk. measered a~ .1835 ern -v 0:11.a sp!:JClJ:ll>Cop:y 1l:'1!C3Sl!reIl1_el:ll5. FticHoll vem:L~ 1000. OO!U' me: of the SIll1fl!.';l!ip·, sll.~·.aJJldi envirou. q l.Il] ml'f;ooc ,~:uat \WS Ilmruam.oo. ~llllilcfalnocmly I1H2Sl!reI'I'ilcnlJ> 0.11 H~ and D~oollJilllatccl Sl(U I) IllClll fox:aU Hvcl".>Us D oomparisum: OJldial1Dlon:!!, w~ lfirl@'CWOO]).J:[ ~llifiK!(l.11Irl(') ·~.lIt 2930 cm:-I _d .!!cpamlflly on Si, alllowcd us lOd'clmll!ilin~ saJlnph'lS \VGIJ:'COhlfllDllCO ~n dry ~N:i!\Milh Iil~@ S81t'lfl is a"-~~ntIOO to dIe: H·oormunlll)~ C~OO] )(2:x ~) llll'hOiltl!Ji>igIl09Sly \vhedti;;'I' ~n ismopic !\liilb,~ilt~~ion ~lkCln ni'cride: ~i:p. Ah)m~(: ~ I)ClIfl1r.'l9n'''ftL-" ~~iOi dbs~ed {Fi1jl. and '[ab!e~), Willl ~~~ ;) lroool~dion (20},.011l 111¢deule'lflIted 8<lIlIP'C. a ,effuc! ~m:d,

stiffim1'lS k. II'I.panic.ula:u, (U ~ Viilii~wih10re ~l ;~ 1I1():I~I(I¢OO n~ ·of'O~~ oondoo.~mat~ b~ I!~ ]imil of h~vy t\ub!;lm!!~ ;:U'o1rn!1.~.i~ .apJW1J(.b,1!It~l~ylhcacl~fIMUe's lna~, m. O!1!d)~no!ld, l!iIlleir.l!tLo· Qif the 'l'im'!ll~ol!ml fre,qlJlernc,Y ·of Hi (rol~) ~d

't:laI!IJ!C

Slrei1~fiIlS were :rulici.ctn .fu, ·0](:; alla1lysis., bedric "1Ul~'~P 'was always used to,oo:it"IIUli'!.'j

e:

riJm~

~OL..Il-0-2-1II..!!.O-O-·-2":'2[]:-~O-·. -2-,sL..'O-Ql

ll2· 2BDO :100'

[]

o
2900

seno

3200

UHV

Wai\l1€lli1llli1fl1DelT

(om,·1i)

IFiy. 2. ItA,) SfG :~~ectFafe:r ~Iille C(001)'·H (f@d~ .affll[j ·10 ~Iue')'sl!rfac@s. Bolli the (.:Ii and

IC·I) regiolllslIlue ~i~dllliderl fell' ~he d'eul:er<llre,d smf.i31Cle to deDiiOilll~trate' :the CIl!lIIiIp~!ere' l~ep~,~(!:mll!fI'I:l)f' IFilbry I), (0) .A\I'eillgJg~ ~'~r\octhl"ll!sh~<:!lrs!berlgth (diIDshed lbnes) 1~,egj$liIt!ied! .~.~ ~2: an:d !.!IilillVall (1(IOQ1)', aJnd Ire~idu1lllsfrgm fits klr '(:.1'1 '{sQUd red ;~ymbob)1 allild (:·D l(open b(llJIe syrll'llbels) measlJlrellrnelllK .-5

10

5~O

1:5

Load (trruIN)1

REPORTS
~~~~]!f!

~Jl;)r

,(f,!'l

l!~efll~~!'!~il~lliOO~mr~

~QQmJngw fge rut1Q t30 if: 1]'.09'. lIihe(J~OO l },H. I!tnd. ·~IDI surfaces lliaw nearly ilfld1r.s;t~rlgllislmM.c wol'k-or..adl:u;:skl:1ll valnesin UHV; Q04:'I.\'l~SiOOl wii~ dH.~e;.:poond! b.ck: of dmm~
~1 oOtiIt:L~ '[lte\vM
1!1Ilii'i
t=

Cif~adh,esioillwn~

~ii[

!,a;~s:e gf plir,e varn d~\Viiat'5ijn~rac600-~ (lS, 19), p.ruwl:iJrly for I~ UHV!t'iea~~~~:i~ and display Ol.fl!~fllI~ive~)~ Sillman dwt1il'o!1 «J%), 'g~clll illonfl,y c,1tpootoo. for well.~:
ffilifacrnl

:i~sli1lb,1£ ,ell\;1romtlCililts. \\'c c~akllil ~nn dtere i1il no. iiJ1lhm'Ci1:~. chCi:bitle:afl.

M'I.~'I;~ 1[[1(; H- 3IDIdl 1!JI..1~:lirh3t6~ sur... f'a ees, TIle l\'IIl1aI~illti!;m.cti(li!~ cl'ectlW!f!lll~ 'iSQ!Ol:}jcs.~Utl!:lio.!f! ef H widl D.w'I'!ld~can
COIilItaS~
~<J)'!;Ie COl~q~'lQes

rO:Ii"!{ery·kmg<llQi~l

~ollyn1ieF

syS!Jmns (30)" is ca:loo.1iatcd 10 beinflfnj~esiin~aUy .m'llaU 11m:: (31)., Dm dilT~rent'Cfj ilI~ 2Jdile<>iOlil 11191 W~ doo1t:Jsru'\!'~ lbet~n H- 31l'Id D-4::crnruiillll~d! ~1:t'!1P1~ (Table .1) do, It<l( vary~$tcm:,11li~ty~ AdIlesL'On i~l~l~!cf fov Hi on ((Oil]) if! Na, lo~){er wll~ "~il~ i~Ute dYtll;Jlfllic:1!i1 cffect!'\I!!;l !1l:!L."S of for Bon SHU] I)iln N~, <ilJ!'Kif!I::<lJiy iH~ dlC: 'lip. III ill Ilihe dmnpi$lgoCmst3R( of ~liIe diSiI~:in'gJJi5hSlibleor qDOI )h~ UHV',. The 'ISliI:£et' iI~ltet:octtion. om!!. uis tl)!o(~ f reJJOIlive sl~di'nS velocity bcl:W{.'C1li Inlm: l~p' and ,!>a1ll1ple.. The minus :sigll 'v2W:ialio:~ui.l~N:i as lJo:mpared. w~th UHV:ilire ~ml. Inlmlf:ri.CiI)iou l3irohabl.y dille (0 \!'.rul}'nng d'Cgro(}.~ of OQ.1ilI:~Wli.na,. (oxdudccll hooacfoi1il~),iindi~ I~[on ffiiQm 9jliilbl~rnt m,Ipo£um:..WG also cnwl_~ ~bro(;l OpP'li!'~ LI:w'l di[R,".Cliionof motkn n~ !~l!I~lbcr If adsoroore.~ invol\Ioo i'lpmPQ!1icmM ( O~~t.~y i!!~~o1f! fricli{J~ by Lheoo!.lI!att ~ 10 llliIe iJd..~roate ~1 de!\Si~¥ C 1!!ld l!iII!eoot!lbCi~ (:i!!loooodl bycl~!~Ses h'l! adtiJesLQ!]) ~l"'<; breR rol'l1oveCi b;}1 11imdiuf!g 'the ,clflOOlijve :shear SLn."1lgU~~. ~1l il. When .my vllrialion ·(If '!lCliWSCd! by nO!I" uniform OOlllact :s:u:esses us; llIc::gj.oct()d., lillie to12Ii~ 1Il1~ n !no ~kt~mg ~O'ID1icmllu:eamDl1i5 Ih81 ~1ll1i~ diroc~.oolllpaMcn w~ili,dlesiil e~rimIll:'IIs:.. V!ihra~io;n8J~coilmlhuuo:1l wi~.l '00 F'r,.,.,'IJ, == ;!'1,I,~pl100A,
:1.• Re)utts. fOir IIIIU1:~lIIlremlmts UIII di~\:tmol1d and S~: thM2'work. ef a;dh~io:1iI (1),. 'liifife·rnve Ie') snd e-~tili!'laited (,,~J!':>~il.af $tfei~giililit$.allildith~ii!i ~altio h~~l!., Ttl e ,~fil·~~hei31r ~.tireli!g,~~fu$' ~1~mlail!edri~1iIl 1iiili afpic~Fo~tQi'l!~5il!lm'efCiUi (COS~I tf"ms.mO:ifi flit'!; (9" 23). IJJliilClNttfiflttE!S ~orrespci't(J m~hi!! ~'1iI d'ifllrdi l1!r1ror ll~liI!! Il!H~<1IIIiI', m II1legl~ectil\:g~lrntiltk Il!Im:elffillinties. S:liil'f'iI:;fil:,~li'Jrl

:~."QI;!~I~ p-l~~'!ic fgri!1(err\1:'C~~~rri.c'iQ~,.dl~ ytJJ~i!Qn<li~ Q01:!iribl,l!.nlmu;i~~r in~mc~if!£l !:lm~tothe s~w ~t!'ern~l~ wi~l be wtnh, a SilI'l,gllc~IMV:~lllg surtlil'lce. [Ftk:llon ari~s (2) rronJI kleJlmst;.o co.~lisio:ns, oot'WlilOO vibm~n.g ad· mfbai~cs ,arIi'Id tile :l!l!Ifr1l!oe.. 1l,Jdmugllil this :sil~lHI' l'hedamp:imIg CQ.iillllnflll'll 1IJis l:'C~alMm th.edInJsi~.y ~'o:nd~ not oo~'porld ,d!i~e~lyroaR AFM p m~,jdU:I~~~~ i.lG~ll1d 'l,'i3~oeily i!T of d.1C: !ilea5Y~IIiI~nt whell~ confil~cd ~UO'Jh5 eh~n· a~ mOcvirng ~rflic~ by is~ed to ()!!Ill ,~al!!fu_o~ i!i:[~l\i'i~d) <lJK! ithe 01l~f (3) !ilOV~ S\.!iri::Ke ~!~er 10<d, weuse i~heli;~[ !II :p.mJL'Clldl~ qual~tati:Ve ~haviOf:. U'Le AIfM lip 'Sllr.'IM!! aod IMClS ,nhcpilacli: o:l'lh~ m:Q\lifl.lli!.ilmfooe, and Ike H wh~re n.~ru1doorefl.'i" 1100 ~~eacnsor:oot~ v.ibmliolil!l~ :f~qU(mc.y.r{~Jt,'Ctively [e.qI1Qti(fii~S IS (D)!iMllitlS oO-~i~d IIi Illil.c OOooi'I!:Ja!~cs,"li'hioCh and 22 imI. 1(32)], .~ fil(iiMitch~!l!!isorbOOl\) d~ di~mondl orSiSl,lb· :snm ~. ta..-: . • _~.. 00 k..JIP' Oillle'~.~ i.! - rnlt.~I~":" ~I'I -, ~ !i.',g _. _ _I!,IO,L_~c\!_·_ To ml!l'Uro~e l!Ii!e p]!.y8lC8: OO'hindEq, 3!, CQIlUle n!Cide~)~d :a;re iiSSli!mOO kliJe 1!1!f!(;oopt.ied sider .an.ad~rbal.C\i'ihr.iti~gwilh C!!.Crgyi! 0lf:'idI [mlill one <ill:olhec: 1m tbe [1l00FY, ~le m01!iOH Coree oo.1UdJ',g wiKh Ole :~mving !lUlrfaoo (iI11te AF'M: Wlil'i vilbl:'lIiIiOlilai. ,dm.n;pll:ti,g by a~cacl:\>orOOlCis tip), Durii1\8, (i!m,~'l!'ib:~lim;t:C)le~e,. dlmadsorbMe bi'aiitsfeliS{'i~a~ AE" ,~.'lIMs.:)lS frOin ~lli"G: tip,

.HQw~u:.Pe!lit5Q!~

frict!oHoor

,m

(6)h~1l

<l~00'b<i1,~

~J.;;Y

pt;

i ""¥Ii (i') E. [iIIld:leooliHsioilil. 3. 3.

where .flJ(~ ~~ihc nms of 1iI'I.@J [IOmOi~,of 1ffi'!!L'l tip ~;Il~li'\'clyinwlv~ in IhcCQU~iolii (3J).1l)I,I!.s. the elJ!I~~ tf~8f~:r r-lLe' fila), 'be oxp:res.$Cdi by l~me f
~

.2lltm,

looal,cI.",~,aec£t1JC!ru:lJc[l(!.fo:ml!: ~n [he: tiiP'\?ilidllun. f dis~a.lilOO {.-i,rn Ii!rl,:OU: 'c>orre.~ds. ~i[l; a\!lo:~lillllll': (t:'[iID)" .TInls, ..M,~.,:;::p.(t.'pI'(,fli)". n('l Cltergy tmilSf~r:~ ~ !I~] .. .
(4)

T,illb'l,e

Tlm soL'tiJlnJlll to Eq}. 4 is an cx;po:lllenti3~. docay wid.l d1i!n~urn@: COl~S;la!ll 1il: == (lrffri)/(.2:r:q:J,e\-l. ~nmih!$ ~o l!I~e'1TlQ:ie p!li)clse1ydCrivod q~ll:!ilY tUn Eq • .2 (6). Bec.m,_~.(Q 0:: !.I;.~a.11;,1['... ~nd Fi' 1111. '
sealeas
NlfwL:1 ~

11m.

m!lwri'a~.
It'lJ,vilroJ'lme'nt

"t
(m~~.nl~)

'1;'.,

(MP'Il)

5,6.:1: 2: 41:;i:; :2 liIi

D 3101::1::: 2: 25.:!: :ru

'][22

fJ7 :;i:;'5

* :2

1010 :i;.17

806 :;i:;

as

.Zl1I:!: ':Il
19' ~ ':lL 'illU:I:: '7 ;86, ::1:::4

:;1.1[12' ~.U 16:1 ~. 7

680:1:: 40

his la:npooi1;~nlo lm!CicrsnfLlilrn: how dam,plllg leeds 10 fli'iCtl0ill at IIle Iti~mpleinl~rface. S.Hd~ liilg flli~ocmis Cll'I!I$'OO by l!~fJloss; of tip 1.~1Q.o m~~hun to 8U1mf.we <iI.ocUl1~ AlOI11S,e.!I1ci~wbyd]c: t!fl ~I:! ~m:'i"5f'¢f eme IQlhhei!"C!~ersy b.ld. 00 Utt: s tip-and heJptl: s~'~pw tile nexl ~posm.on" T.his ~ ~J1lii n:tI" to ~h.e (lQlKlCpi of I.-educed! :frictio.llm. imcresstlflg ~.cm~r*m <3'4). [S~n:i'b'l!2rn: t al. e (jj) <IDservOO ihl~.is I'OO{ of!oeaJ~ized crxcmatimlS ~
Inri loo1.eenlklr d~!'i!trl]~e,~ simlJi1aliol't"'t]I\Vhm~dtiil 5Ui'fice ,~u1ial is 8yu'm]:ruac.d.l~e ex,c~ted~~r~ racc <JlmlllB,kick Ifiile ~ip :~~ fUl!"I!Iafdl <!!1dbac1l;· .he

1m3 169 IFiig. :~'.Avel1!l[ieIMEd:ve ma:tlr ~!Ii)i~g;tIiI (d~oo Umm0iiI1 :$'~1l!1)

::I:: ]' ::I::

'S.30:l:: 20

(lInd resirll!a~$ frOlTli r~~re:se-liltaJ· ~or the' :5i·[j-j (8d~id[ red :wm~,l'a~dl :rjr~' (~IIi~en b~~ syml!llols)' i'IIieilSi!lrement$.

ow ·fits

w,;;uti. ,dJ~~lmlS, ecplmlly ~~lotlnsam[ opposing the ti~s m,olioll. Cillfimever lW'ist :add S~ bi~ to ~Ie otherwise ,syI'l'itilmuic .IXlJflllntiai and :l!cr!'~ts. ~e energy w'CU 3~OOIg I~m.e:Hd~ng,dtucc~,O:Il (36). s Co:nileqi!ji:mtl)';.lh~ moril'it\llliU[lll:m1llSf~d! back !,g,!:he ~ip by .s;lJ,!rr~ ,;;uiQn~~il:; !l!Q!Te ~ffet;:li'!i'e :~!1!

Iii=:
IWI

..w'

50 -4,

~----~------~------~------~----~ ,-2 0 :2 4, 6
[wood (mN.)

r~f'I!~!<lJ:dd!!l~lij;o~, 4iIJtd m!'fuQe W;QIl"!5: !C<lm help :p{f!shll~eli;l) ron~'ill:dl" Tlae' ~"'liliil~!iecn~ m,do, so is md:ucoo, by 'dl.ecflergy 10(;lm~U slll'faoo atO:Iin5 In tim suhs:trn.m (1haI:il;,. dru:rrapiflig.). :I:{'Billec, alill(ifuglll.dICr:a:tL;: of ~NdlauQ.1!l ""~.$!-flI.. v~s 1h~lipiillld ~IIf:ao~ riMy be· gQ~"fIl.eJcl!byLl.1~ altemp~ &equm'iCL~ of.lie swface~lom8,. Uie &mffiJlltg 'OOIRsl;i!lllSrre;presem( the dimluished <lbml,y t(l~'litlnSrer ellergy ~!i1cktodtc:lip,. A ~I of otli'enm~;Y timl:'tSrnr ~~memlS 2I!m !!il!liJPOi1l'id, Ill"
~le

1n.0I1~('iIll~iW dy;n9iiiil~.cg ~iii.1i]jL\ltiO!i1."'. whi(]1iIhave

(!Iooe!"!t~H

'~ledh.l:~l
!)mK"lOe:!l

~'Q~

REPORTS
s, It,.V. IPIl!l:. D. F,. Oog;l~tF~!!', . A. illM. M. !i~n"fi(!<~~1I, P SdM.e 3:l.J. 1.86 (2:Q;061. 6. ItN. ],.~r>OOfl" 'S~''diRgFiidiW!: J!l!.r.;iml .Mndpkt; U!II'dtl,!;lptJCOlilln.!1 ~51lf~r. Ee~li!"l', 2.200Q'l, !lid\. ~ ;!,a2~lla;9:~ '1. v. A~, M. ~~ttril. ,M_ ~mo. 'V. S!ltO, !O.iowt. Rel.,\\l,jtg.r_ .II, 6. S. Yt! !]I d" s.!1lt '$(l 47,11, l:li[ ~IiJIOi!J. '9. SUPPol1lmg fIliIt!!!Fl.a1fl! ~v.i!lill!!i}I'@Qm 5r.li!tlt~ tOmLlil'!!. 110. A. Gohtbo~~" ]1, P. TOOMnies. '5" \t'lIllITiler. S, II. ~lI1,~(m. l', s. S~~fl'cIlJlid:, PIi;!ol:., ,i!I n,WCN!~{1'1~.81 kw:, H. :5. 'flq~d1~~!! e~1IiL. I'tly£ Re~ 1:l6!l;. 1/.!~140UR}(,'0031 11.2. !1.5<!lII;ifQ!1~ /1,. ~~!!!". j, ~~~~n, M~ Re~, .fI 51" (l!3~
U!;I\\lS), 6i!I] (19'1l'5). 2~9., J. M. Ilm~l1!fti'\i'lU, 1il1(!r7!'iDf~{ij!tfl' if~rd 5iJ!tf~~ FDtcf!}; tArn:t:!tI1li( P'~s. tL:OOdbll" '{1t:!, 2,1992t 2~9,. A. '!J. 5ulMm~ Ill' i!flt., ~ Mtfl. 1,7. '1:,0.3:9' (2005'. 3!1 F,. S. Batl!!. G. (JI iiI\i!:lt~lI! W,(,. K(t@lnl@r,p~ k~ 11!U. 111@~L.o!., U'M,r(!j'~Il.y rn' Wlmlf~IIF.M<ldi!un, lila tli5Q 11, WI (:l,OOS). ~2. It N. J.Pfll'~~tH" E,.1:~s~tU" I). IFu~rnl<lFif!l. til", ctMttll!. C, !fI\olt iNIy/i. i\tev. tj!' !i9. ]:,]'7'n (;1:;999). ~,~, It IE"\\Ial klJjl, O. M, 1Ne-wns. p, A¥D~ai~, 1mAr~flir Mil' NIiIIiI~Ii!e.ri\l'·5atilie ~10\1iJl'mrf$ll ~tMli'.!if'ftQt:!i: f<llM~Ii'ill;,tJ.OO ~&(j~~~, fl. A'i'aUri~ iii!!. (IUllwe.r, ~~!~~h!,~~Iu~!¥iI!'!~,199,~l ~ UI(i', 3~, ;(,Ziltal), M. IHl2ItniitoIil;W_G,)a\1,!j\ef,51, ), Pel'l)'. !'rilNf,/, J'.8fit~i!'. nl(2!OOn 31,. M. ]1, r!rrukmam.

:S~id~iJ.lgooltk"l(1t {.til l'h~ dalfllprng mood prodJi{)iI'.'> Fl~~~j ~} F~... ~ for dimuQoo and F~n~~1f~'ic.:i ] ,36[0:, Si. F Olllti~ilddii~i,ve. :ii1a..~.i~~~p.'ttd~mt oonlilt:ibut~ol'b~ 110 [Mcli(1I11 ~Iid thi.~plt(j'1;{l!,!!~C m~hal1!~~i wi~~ tNdiucc jh~,~s'!.m.":dF.JJt:t{i5 fm!~ Ifilie ~hrore!ical f!redicI1O!lS, as dbserw'd (l"olble rn). 'I'hepred!tc.l!d -'8% differolfliOO in ,Pr~~iIlJ~vib for di,rua:lO.1ild. \rcf~ sus !iii:!> wi~D;iIi1, O'l!lr GXpecili1lOOt:a1 IJtUlOOf:taimny 3ndI1ll~:lilJ;o be (i01!liiitcrnmccl by lite il1>Cr~ COtUpHIlS ,of slDl'faee ",ib,,""i(li!~l :moo~ 'lJ!f d~.nIHi,'i,rnllXflSi{:1 11) 1[0 ~.nlk plI!O~lOl1.'il 03)ac<; 0001~& wiJ!~l 1'!y~SC!~a.'OO Si(l~, 1) {i.2). Ond~uo!ld, suA'loe :~nodes: overlap, Ib'l!!llc'hless witllb:ulk l;i!h.oru:ms rJJ),F"Unlt~:r.1Ore" rcin.mtlfll!: tRIe a.w1ll_nlP~ t~im~ I!hat tlmae3dso~::!itc:s aoo lHIDrru:~tM (dl!ll1 is, C1~:sidmimg ,ooulplt.'tI d('l~orn~.i.il:{)dJvililral.iolliS)
i~il

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p:~dJicl~ ma.'li.'JI)an.'lf$t

(12), U i~ tike~y, ~owey(!!', t1~ts~rtare defcc~ whll::h aeec!~~l!I.ate!JIi!e errec~ ~f ~ocaU~dlv:i~ irJlratlmns (9). are preSl.'m mid ttlIDY C:\I'e,Il be the domil.\itin~ cmuribu.t~OIl[0 odliSsip.ariOfIi..
R@fl!r'~iIl:!!;'!!!laIiCiI N~tI!s IL. ~,. 'Ci8pa~1:; E. rD. Srnrilb. M. Q. IiiCil:illliifl~, 5(itJXle 2Jfl5., 1.200 0!:994J. 2:. "C, ",<ilk. C. IrMl)', .~. Krlm, rlJilll.~at, 1I1:m:. 2!l,~.190 (19914'), B.. II, ~.,JI, IPffl~, )\.1.'!Jir.olok4!if), /. '~MJ!&~G3~ M:l'9 U,9'95')' 4,.~, B. $r.oklll4~ p,,~, Rw;. e 52" ~1S i[:i,WS).

U~'I.I: Griisdnus: A, J!NIIlIIf; J.FIt:l1lmafl,Swt .~ .168;. 11'9 U'9116..1 n..c.. ~llililm:li 1m. IGi"eogdlfn~. 1fI.. lbadt P~J& n't!ftl. 8 45., 6M6U'9'l!2). 1&. If"('CII!ilIlg'" l..-c, ~rn,..''I'.t,'I'u, K.-liI." ~1I,j:. j Ptlyro Ch,em, 9" 110811. U99St ~6. (. t (me~go" R,c. tljl:!, HI. e, (J],~~g, 1 ,K.W.[l~. J,Ch~m.fi,h~:U)5, a~n(:1:9%1. 11, T. Mtoli el ,ar" J. Mal. 5i'1l!C!. )'52:-)153\,. 4,s,S U9S1Sl. 11,~. RP. Oftj~\ ~,'f. l!fI1!'~n9. ,!" !I,. 'Sht;r!" ]i,]. C~~f>l" ~" S~~, ~iV~ !It~- H ~2" S91~5'(l99·~. 19. It ,Po (Ilim eJ at ... fJhy!_ Rw. Ifl !l~.1:5cl2 (19911 20. t, 'II. zm~!llJ!i, ll~rliI'!'I5lllW!. 9.1, Ga~r1!!OOi, 'SiIff/. .'!:d. ill'lI, .333(19~1t .11. M, ~nil{htg;u ,9 ~d,.7i'j/ja/,kit :iI. ?,~b~99J, 22. I). S;, G!i~oo. E. e. E'late!', R. W,. Ciirpitk, ~ AtUl. Sa. rMl',
U .2~1 t~OOS.l

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36 •. ,6. A 1i1lm1lil9iili'l\ ~.~ 1, 90S 'ti!92.<)). H<lmiOm. C, V. Wllfl~t. R, J. oCIJltOfl, DI,iiI1. 8ftrmer" 1NJ,J, SMd ,iI':rlim ;26iO'. ,2OS ~19'9S). 38. We- alill!!k: .~, Ilill!lI:tr ,f:f!!li ], 'ralil!! fer bal1!iflQ .allId pG.'kiliimg .I]je (OOlhlri~ ~ll!lliH.~<i1 diial!'!ll'~ .a!1dl Jt!:f he~!J ~.~ ~!Iy H U!flmtmli!l'l. ], ~tt!~ ~eg.

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'WEm ~~ii'ik L EHlltm ,!t:il ~:JI!~fi~liJt! Kid 8, GalSrrlo!lfill! for ,~ rn.tlplll~ re2dJi'Ig ,or ~lis ~ppOlt.to!l bf lill!ll ,t4Sf CAAElEII:Award IlI!l. ~

t0134S7l1; iii! N~ GfiHlwtll II\f1re<!n:11 Fe~~imll !oool\ir .I'«"~~ orfj~ iII!SI;i~tii~~ ~~tII, '~f'lln!¥\9~5~l\-(iI;2a.4,

:i!~. It, W. C?lrpid:,. t:l. Fc:, ~en~e:, ric', :~llT!Ief1ln,.j. ~l/~' fIiW! S(i 21i, ~'.5,(l99 ~)J. Z~. Il. ,LlIam\. M. O. Rolllllitl5, Mat!11I't 43!l. 9.2:'1 t2!!1D!lJ. 2>;. III 11l1'lfi.,. ~ 0,. ~lllilrl5, P1:ty!,~ ~"'" r 7<1, 2:~1l'l. (2100ID. 26. U. O. ~diwHfZ.. 0,. lWoffi@rr. p, Ko~W, !R. J1jirl@~OO!i!fi!llE!:r, f.:IllJl'.lO ~~, j'j' 'li:6" '~8l'(199'7]<, 27. G. ~D" R" ]1,C~lDIliira. !t '!N. Cal]lk:k. llt ~~ui5I:m.. ~arr!l'm~;(r~:31 S~~4 rlOon.,

9M)' 200(1: ,ltwp!M 2:1,5~pte'ltlbef :roOO 110, 26!$t~~tUl<!1:S,50, U

di_roc~~ !rn100Olji~hlltk (SJP,:~ C-H bonds. O!Xi~~ tlm~ roact101~s: for JSo:lailDdi,~lIac~.vated sp::! C-li: bends (l~paihle oropeuat~lfIg with IPred~ .clim:b~c seI.oolhlvcies Of~ Co.n.1P:!C:XSlJlMmlrus hold. s:pL"(lla~ proa:wise for 5tj'f(~[lnl!iI~~ng synd~e.'>i':& Such rsact!O!!L5 \!I'Ol!.!I.d pf\J'\l'.ide ;J ,g,e!lcrol \¥a'j toun\1!~IIO'Xidiz:edim!!.C~iona:ti,ies at D" ~"ltstolge,. ~!he~by rOO.!:wll,gM!\]poodMCIiYe cl1t:'!nlcai mll!~i«?ui~atlO!!S 3S.<;ooblll:edi w~.tlilc.9.l:ryingll!cl'l1 ~1ID1Jgl;la ~ ~~,~!ri!ilgilffile ~.1!fQlQ~dnlli3:ry pate~ti(:d !)If !l!Inl!3dii,tQJ~d sp'3 (~ ~d 'oxidati!O[!1 ~~ @iigallk ~ynth~is: qll.Cnoo (2, J)" tretJliJ!iti thE! (iisw~iY of' Ga~liiW that I'lr1i! bcrtJ11,ighly reifK~llll! ,a,:lfidl ~r,edktl~ty~~emw. h We ~jrod an .DespiiLo lilmiporna11llflldWllces in. the ,dj'500Wry 1r,011l {Fe~flse(1j! 5i'I1aUmelecld,e; catalyttlIDiat tUses~rogei1 p~tie (I\O',zl ro, o.xice!li btroad r,aUiQ.ecff ·of.cal<1il)'d'Cm~D!Jw~ OO[<'Ili.~l<'lti~C:"'H Ix>nd l'ly~uOObiim. P'n!di:ttab~~ .W:1.ectMtyi!l~i!!Wd' :sole~)I'iori tlire ba5is;. of Ut~ el.edirook ilnd. mlirk propel'itiles g,ff dro;t-yli!!~Q~. <l.lilli!~:t~!!S"MdI <I!k-yI~~Q'U'i,(4':"6). ~liIe (-H bon:d~, 'lItIi,tilIcmt the mleedfor dlWnmg! gmllps.ki~iitiOl!la!~i)f, (.arbox~atie: ,dlremn!J g!rlOu,~~m'<liy !Sel~lh!e D;;:,l()!l.vity wid~ mn-.'I~ S1JDstmles 1:1.1'5 lfureU5/M to fmlili~ 'fi¥e-merrnb~red ring la.$ne pmdlllcts:. 'We. d,em~~raJte' that tl'1e!leilililree' nrtodiE!!l1 ,of g~~.ybc~!l~lIDl~tedi f'Oflloti:;llled C-H ~ds ~iE!I.e!i:~ ienable the predirtab~~ ~datiM c:l1foomplexlii'!)tural p:mdijc.t; ,and 'lheirr d~imlPlti~ ,at :sp~f1!i: (i.e., .adja~u~. tOfll~elCromOJiU Olillt systi(.'l:tI) ('l-U) (-+I oonds with ~r~pa~artilv@~~ til!~~i!l!lvi!!~~s;·'tis; 1iYP~ dg.@III@r:aJ and Pf@dr«abX~ regjcij,lAw !tarld'~m OJvU8J dte we af s~ dir00timg groups V'1-14). le-nillreliliptAatic (:...:H OiX,itidollll ,a,-s: iIImethotill ~or' ~n~mJiin~l1g WillIple::c mol:e(lI!~e 5Vfililh~iS. Mi.,.yi~M. iI~g QXi..d'a..do.iQSof .•ilk;iI~loo.liln.acti!..?l~ ... " .. ~ C-H &lg~&; .~.~, ~ndp:ngdlL~!ib~ 'llf,;~gi~!Yi1!y h~ Q!]lyooe~ s1~O\v!~Wi~,l ::>i:mr.:lelQ!d~rbQIIl :I!..e ~(m~ c~nl!.!fj!' witn~ed treme!ilOOM ,em~leH.cy. ,BecouMile Jlllili!1i'b:tQJQIF:l~C<l!lly t~le.\'@n~ WJ'S~ (10, 15-.17), The ~~iI0'x,klll .cIm!.wv,moes ill S'Y!1~:lctrc m~~lOOs .m&!~t· SlIll"n ITIt;lleClnl.es.<lIN Q)'!;id~zed IJyg~I!"',!lf:(!C· 'egjes;!llZtl 'h,!ilVe ernab:led s'1ila!~, nullec",ite lio(IlJ1S ~~,i!!~; iI~tlOIl)!,1mte oxi.d!~cd.fUlnctiGI~lllit)' leng;ein oo~vi~gll~ispr,ob~elllliesilill di:sooveril'lga c.."ltaty...~.'dmt isooih highly m."lc!rn,V\eand prod]ct,.. t~nrgcts O'f C1>i.iJl'a.o:millill:Y conlfl:~e::dly mile! bio:lo,g" ~l(lCI:ivcly ium, o:rgnuicfi:nlIllCi\¥Orks are orpal~i(}; aMy;sc:lcclivc fDlioxidizing lh,C5~ linen m~d I!Ibtqt!.lar mll':~ :imH~~is ~d.'[h:fIOO gmle~l ,R'J3Nion ~calim~lCC '1.0 00 s;ynl.hnsizOO in. 11m ~3bom,.. !wry (il All. i:~nporlant .oom3il~ing ch!1!ltcng02l(;, t~fi da..'>S~hllve b~llI dCNeIO',ped. for Illiln~1P1J1H:pt:nS(l;: uil{);tl.q(;-'H bonds, M"feoOV~. tore l!lS~rltll~1iI OOlt!iplgN; !OOle~le ~y,"lI1:esiis, !his rea:ctivily o1.J"idI a~I~~~i!l synlffil~~ W~!i!iI hci~~t('ll1i~ le~~il ~f fijncl~mla~ w<rIllP ill~f'OOlweliNlm..,C-C ~d,,fonning :!1e!I!cli01'!s Oif pro(I'Xidiitedlta,Si!~~~~, ..n_d !5ele-clivitylll!.!5t be gle!~~ ~r'O:i 1.!~mtdt.iJ!~ of d-el\S~jy fum:tioualize,d, sli.lbslfilles. Nai!ure'sd'e~ ole'fin aI>iJda1:~ons:,Wi~a these ~t'iml5, nlodetn [lI'e<,JlO! i'I),I'!en tot 'Chemhtr!f, Ro ge'l'ManM l~ oorat~ry, S1i.jili'ill1cip~i.1Sfui' OIi't'aung sm:ih aualysts: involve s.Y'lfS1le~icJ1,i1Ulli,[~g ()~~1 ce,~il'ers 1ID:l1!I1J:d, tli.e: lIIse [ IJln~i~,~ sr IUim(li~. Urb~liIa, I~ 618G-lj USA. d~e 1!I:E1.': of Clohor:liII!C pr:otCJin.bil1Kijn,gpocllml!!! tdmt ar.dlli'lah~~.ooru.\OO:.0:1' 1Pme.:ris~in.g o:;:ildizt'd. fmlc· 'ilio t~hlll1ll rorresptJllId!!IlIQ!' :~hol!llJ!l b~' ~!lIre5sl'd •. E-mail: ~hit@@ocuiu(.i@dll iii1I~~i'il\"tIlily Hm,im. stIlb!>lm!e~i~1il,. A d~rr'eroilll 'l.iio.if!!I.~ily..A p6wcr.n.IJl new c]ass of roaet'LOilSis
1

A, Pr edic'18IbIy Selle!lctiiv,e Alip!h,at:i'c Ie-HI IOx,idattii,on IReac'llo,n lo,r IClotlmp,IIIB'X MoI8cull'8~S;ynths!si:s,

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1f!i!!'tClI:uQ~~lrUy

REPORTS
~tQl!eID'wa.'5 51i!gS~W,goo
Q1!!1

~s by ~"mim!I~1I.'~f:k sll.e-se~,ectlv~ glef!m! o;tid<1~iQns YSt~g b~~kyj' eiectaro,phHic ;IlJcmlcam,lysl$ (18, '/9), \Vithd~cse nmgtmls, miOl1t1,.ox;idalni.on ofpO:~yoocs oce~ ~lrOOtcm:bly at ~~.c~UOSlO~OO'ljl'(!'i~,~ridg, least
~a(jrk'al~}I I~il'id~~d

ple~ 4 (2,6)1, .jlI,1,g~g) (i. t!~~!@ b:tupwv~met!t ~Q .wci\lcl:iv[ty (~%)" !!!'ru~latl!."!g h]~QI:l. doobilil'lg ef di.c:y.teldof2 f]4% ytd{l" eutlijl .2).. T.heMd!itiof:l of aoot~.c; cid (A.cOH). ~reviollSl.y dem01ilsUa~ed a 10 il~al\lc bcnefieial CffOe~Qll'epC!x:idMi:ons wi.dl a .1 (24)~ increa;;;oo Ihe caJtaJy'~ic acahd~t¢!lO!rbodj .3 a..bd.4 wid'iowt $ub!ltal~,tiill.~Y~~1iq:'igtilg I!Hii~ir ~J!llctiv(!ies (e!iiWl~ 3 ii!id 4, ~iOCtlV\e:~y), ll~is IleS\d~ed In! oot<lible~IiWm"!;.real1lCl~lin y~e'lds WiOl caJDlys.t ,4 ,~t}nlr)' 4). W1~.erea.,>iltcreasiifflg;ilbr~.iSi~ mJalys.tl.oodMiIgs,. equ.i,V,8J~Cn1iSof AcOH,oi:Cijlllliv.. all.!uDi'l :fH~O~ "lIJlI:iiteer in oombil:L!atiofil) WUVef1i.O o fi,nrll'u,l:r im:,P[\ov.~ntOOI:$i'll j'i~~d.Q(lII",ctiv.e:add~lio:!~ {lif aU tlU'Q;e COIT:lp~!~e'R~]~ a 'pofll1iO!1IWise
Ul!!nncr fUl!1iIisl!ed preparMivcly

foilar

d'{Hnbt~ool'id, .Morng,v€i', n,lnCI~kllt,'iH!}' ~!!~xi lila! t~ ling o,I~f1iI~caiil

d~!!t'~~9~~gricalzy 'P~ I~y~ro?;y~.u:§~ p!iOOi!!G! .~ l~~S 1% iwn~ )'itld! (en~ Sl. A. pue:l.i1inil'wyi1ilVflStigat~()rnl of lhe s~OOtmte, seope .higM~gh;1s die SdOOI~i\'c, e~ootropiliH:CI'la,. WIre of tllt~ (lIl'!:tdaJllt gellcrnloo wi.dl 4 3il,d H~O~ (fi;g, 3), .lim anca.",~~alliim~.~ Wlydl\Y.xy~al~om
O()t~~

direct oili.ldatJOJil,ovemdli~g e_~cb;(!l!lic and ~t~uic e:~ecls:. We hypOU1¢sl~~ dlilt sile;·se1ecHve Qix.im.titmsofu.lllac~iva~cd S:p3 C__;H:bml,cl5 c'oold Si.ll<I ar~ylOO::PfOO~CIal1bily iJll1llIro:~loo if a Sl!l,~~l'lb l Iy
Irca.et~v@ firliCIa) Mnai~j'SJl (iould be disoo.v.Qi'C,d 'd~!II~:!l ¢a:p~1i:I1¢ digcr:imil~tLI!IS: 'iI~¢ ~1illle c~eClnronl'C ,of !l!ud stene ,d:tA~!~()es oo!~lJCe.. (''''''~ oo~c.t<:i!~ CO!'l'!p~exn1oloouiles (Pi,g.. J). \fu Mrei!1! report an ""1 """-I''''''''''~ ..~ '-1''''''1',""i~n"'~·"I·· wil",. iLiI, '!iJ!'W '~,;,F '~~.o"""'nit;,!l; ·of. '_. " 1..:""I'Il.\1' '~:,~~~".:I' J~~I:..I'!!H;b~,r,,, ,_'II fnl:lmcw(D!rk 1lI~;a(1II ses H20], anim.:lx,pi'l'llSivc, C:lwirolrum.CI,t~:a.ny frrlcn,dJly Q:d.dru'l~ to ,c:I'l'OO( highly :s(l"lseti'l,l!(': oxi&ri(lu Olf ~!n~3eti"'!I~cdlsri
fl.,-.;
J~

b(n~d.desp~~ ItlI~e fill;;t 'ihat secO:liidlJry(2.~)! C-Hoo!lla5 ~<lve ,ill si§!li~cml OOf~ary {JO)C--H
st:lllljstie@i~ advimn~e (entries. I ro9}.A~lIiLOlII~1~.

p:~~~ii1lian)i <'it

th~!'i'itQ!ill ~1~tfOti·rich

1t1e d1tcal~onj£:irou c:;.l'nllJ~ygl4 ~s..Le\l,Iis .acidiic, a, rmnarkilhlc: I:!}jl~l': of 1:nOO~:r:a~elyte'!!lls: basic SI'iOI;!P$ "i."'~~ ttI!~~IM, FOr~aIn.lp~~ cydic

'f~~n

u._~ru~a'~(ll!IW!l\;

~'Y_'I!

~-I,J!!iT~)I

II. dJ

o:r~~')'t'W",y.l!oA:ed! i~roollici.S]Encci:ficall,j.we,rbuRd ltuU. 'l.iUCiG: 01] sec;lIlh~c:,ad.d.iliolil!li Oil!' cHI:aLY:!It4 0

(5 n':IOl%)\ A.eOIi (0..:5; equaili'::!!();I'i),. 3Jld. HiO~ (12

'LltJ'l!ll.V:'!1lllill"]1 overl!li pm1.oo. of 30' nl.i!~.ai'lbm.cd

t~on, reaction, {Fig. 3)Lln <in easese x <!ln;l~ned :~m. ~(l 3~ C-H OOlaol :is pMI of a sl:eIlL'ilgenic e(}i1I~m·.h,moKylatl(m eeeurred \\,!rill~ cQllnpllcte rn~(\i1I~lm of ~tercoohsmistry (~!n.I!l1i('!86 and 1).
wldch

..mldcs~~e

ed1ers, '~~'

~OOIlpatJb!,e ~~dl !!i!i.s c-'Hoxioo-

~!mtes.

and ,e:~eclro1f!.~efiei~t

C-Hooll1&over

aJ. broad ral1l~Oir £r~bstr:alt~~ that Iil~'e8l~ ·of g,,,,i&uio~.'I,\ljiith !loan ·Ocpre.a:icted '~n com!lJeY! o~nic: subSlrn.le!;on dlC: basi:!> of tbe e!ecimnicMlo. !>liCicic enViln1illlrUll1~ of 1I11e C-H bo:rnl. Add.irlallany; when c3I'boxyi:alC flllllm!oot'Ilil~y ispl\'!Smlt, i~cain dir:l\Ct. (lxidSJtk:ulilI wr\~f:i'l,\\a-IiImnmLMcd: ring iaclol'!elil!1l1<itio!il.

w~deg~{Ii~lrn~e

IPig. 1. WJll!~grl}so!t! bemem

m:e-S€lective olefin tioos and IPr~c~1

rolF

'e'$!1illJliislledllfnodes

S<i.p~~teCl!M! ( ....H bond ,oxidMioos Witlii, bulk)" ,~te!(-

m:ooes

of oxidta,-

l!bHJet.ura1loo
Il~!rOIlJ!)

Scwml oo!dle.!.~le iron !OC!lT1lpk,xes I1QVC!iI'IDWn fj!!lQl.TlI\l:ing, ~creospeci~c ~lydroxybli(m :!IeadlV'~

1H)~iih: !ift~l
iRdiwesbl,l!ky dfi~gl

~~~3.

C-Hoolndns; ill !>ilUp:~1i; mm:c dihydli:xyLatioos ,tAl)) m1,~~t~ ~.yd!jrQcal:'boll :mbslmlC.S (2~-23). TIm:app]ic:atiiOl~ ,cattl~\d by e~droplili lie 0'[ l]agre~stmus: to :preparnli'!;'(;l C-H oxkhl.tcm O~~ wilffil bulky IqllliirUlldi~(lH cherniSlit)' lila,\:lJ~n~v~r~OOdi b},ilh¢ reqp!J! ~~nl d~l!f!,e ligarlds,. dihy~"aJ(.yl," fQr~aQ!;cscesses ()hu'bsu~~teIl'elative ~()Q(!{idal.u, e alliiol1l of poLVe!lIl:E!!i O;t;;(IIIII'S. io·.~' 'C<l!laJy!lA. tU.fn.ovel' mtmbers. :<lind, ~O:]" sepref,erlf1flrtia'l~J art me' most: ele,mon-ri~h d(mllle! band ijrig,liI~ghtecl:inye'lInw~l. (11HIlln .Ai[)',. 'th~ mC!ll:t sternc.aUy ioc:~iv~]'tes r~p:roductromlation". Nle''l/Cr,U~e;'less, ao:l~~'b~ ~~~~ .sit.E!(~llow) ~ dihydlil)~~~tEdl ~r~~re!il.ljdy I~IIII)O~fi]lk ,a~ooho~a~ ~W~(U~d sim<· irott(llru~p) OOlnp~~JJlS [n~ ~sNj\l':,d~~:nc~I~yl.NN·~ selern,'II'e~ with Ma{OO}"" VO(at:;itl(;)'2< Oll'il{[lEtI((}iI"iPr~~."C<lI" a'rnyliltWllilaID~;: DBIT, diethyl.tilrtraihe'. bis{2.pyrr.l(!ylm:(';Ill~yl).el.lm.ne, 1 ,2~:~flmhne] apfCl8rod p:m!ml~~ng [orplll3,p(il.l!rn1tli'llt'i C-JioxklatiOI!,~ with ~o~]pile){. Sill!bstr:a:les~~se ope:l<l're viOl! aneliccl:rophil Ie !~~c:!t!loxid<'!~n (22, .2'.ij, ~:a¥e a [bll!1]ky Ug,.u~dhn.leWQrk anilC!1Iab1~ i!O ~nodlililOatto:n, and ha.rvc OOlCIlWlOO for~:cpara~ l~iveclJ?Oxio8do:u {)if o~.,~I:insool1ltailling :fl.lI:K'JI:.kit'!n,.

i~ics with

IUI1OJo~i.va.ll.'ld s:pl

r.ro up.

, . .p; 0'6"

e.G

L _ J,".,

a.

wey

aHty,(24).

-~, with dectrop'hHuc [fe([n(iIl;]~J.)(CH!~CN)i1'

tile .alten1pltoo. (;-H' (fl'l.idfltlrnl of pi'!,'l!Ilate

(SOPdil CQ'~.lp!ex, .3, lI!~ilCter pt'l':~n:ilive cond~~:~oussub~t!ateas jhe ~!i:lnitf!lllg ( q.cnl)!leS'I.!lwdl

AGO:~ Elltwy ICallilys~ (eqlii'l.)

1

Y:~eliJl
(,%~

eon"", t,
(%) 1:2 15

in {!n~.yklW cmlversio:n of ~~ta;;dn.glll1llerhll (]2%) : and I:I].OO1':stS!c~oolnivit¥ forrtll:il1l'l1f11ti<m of'lcrtlary ~ydfl»iy1atoo. produCfi, 1 (.56%. Fig. 2A, ,ootty ~J Pr$Vip,tLq SAAad!~es,n,8i\l~ ~~OWi1li af'i'i)Sll~iw;oontdar l~i()f1 OOiwee-~ flcxibHii,yQf dl!;) nlep 1~i!!I!d..mcl 1~~e!<1lblH'~yf !U.lOOfl oom:p']el'll;-8under Qx!diIdv~ o 'Qndi'i~iQfliS25), :Se\lil1.lSe n~lectlve {lxl,dadolls ( ~ wi~~~I!u:ndtenlle i.n:m. oomiPI'!:~ fiR: oRen al~ l~iI'ilhu~ed I~QIPml.wn~type: dromlSUY U.porcl C3lll1lyst
dOOO1irlpogil~O:I1I. {251. we h~tl.l.C$~L)d. Ihat hl.~~~ing thB ~g~¢Hiy (iI,f th{.'l,l;'I~iP ll.W'lillldlmllY lead to i:~lp1l'Qved~lf:lec~:i\!hies.E.~.c'ha:~gi~g Ule ed}Y'I~'1i: bld.dge with II c)"Clohe:;:ane iuinglla!d

2:
,:3;

..
~,

3"'

CI
(I

.,

SdeGlL t (%.)

14 213;

3,"
4,

0'..!5
(JILS

till

,51

es

a8·
5'11

fiig'. 2. (10 Deve'J)oplil!if,nt 'Cfill p:iiep;ara~ly ~serul. .ili~i.~hiith: C-H ,o,xidl.alt1ora J,elloll.ioll. PH~duru re~ 51l11lrtiin[i1I'lI'oml IJm5el~edi,'II'e<lInd mreroillrlation I were 'ObJll:1nrec:lliDl tnlI.'E· arnmlJmrn by lH Inlll.clLelIiU IllnagnJeti'c; ~Q ciff~l.. However,iu;oorpom:ling (iU) mel!.lY~~ f'~Sg:!i!an~!!l'(NMR:~I ~f!d '~!1!S(hromiii!tcgl~~~h gm1!ly.sb ~f 1h!1lcru(!i!l !IIel'!cti,~!!i!m~,tyr\!\'. (B·)~t~~duoo ~f aJ'tl'Iif~(\\jl iil'llri ~klJifyif:lg pynnHdnne rifclg5l,\vh.idh. o;!!(S,s~IPDPJ~OH3,CfllJ)zJ~SbF&2 cM..alyst(4)' based 00' x~ray !onystlilogr:aphi!l: ,ililfial]p:li5 (.a:rriclIfisililrre OO1itted lior fOi'fli'illllS c~ih)grnphiealjly ,olimEa.ctmi2cdi OOill~ ,~~al1ly).."'lI)iP 1mdliCBItec!; 2:-·(f~J-2·-[(5)~1.-(Plfr1idil1i-2·y,II'I'I.~1FI~ p)i11idtidilll-a·"Opy.lirlOlilJil1i~1·:!Ii~~ITI1Bth1fiJ!l1ridilile'.

REPORTS
.... ~!1!.)!Hric ~~~yl"~Q!'!. ~~tl~~<W~"1l Qft;c~Uy p",.~~iary ~k:>Ql1;QI5:.!f.! od!l:lbr Q:{mstrn-.;:trng S'te~e!]~C .:1: g .Il!UI;:y~ Q;:n~ SIllooirll;1~ lwl.wMc!~ flQ .3° C-H bonds~1i,fere occ~ at lh.~ml;lell~yhme i~illlisre.actio.m.ei1i a'b~es ill very sumpl.c I.lpproadll f:ot a'i'aihb~e.oxidabj)i1i IFiig_ J. ElialllNl.tion of :ril!!!1.ct!ioolal ~r,(ll.i;~' ((j:~~

w~~~) ~QyplGQl 00

IP1ltilii~ity al1ld5'u~trMe ~mjpein4l.catl~d 'Dxi~pii: (-H' ~,and~ witiil ,H~O~ "Stanmlm cornd•.
tiOfh~"

d~ti@m !(If tJJ~i1Ictiv!1!ood

I\!,~t!il d'ffl~i~

i!lnbNkeio!il~ ~:~lJ!c!vijad:~~ i~lte~ne(U"cy of ill· .:;!.Q ~~~~:h~~<e!]~ H»).. '!Ii'h~ sirese~l'lc~v~tics nnd SDm"lQCjbelillioal Olil.t(lQI:l1e 01' oxicllaliions widl 4· aile oOl1siisk:nt with, BJ 0011oerwci. m~I1{l;I11iJsm moo.tared by .am. Ifll!ec~pb~lic IDtid.all~ (1'1), n~!lla..'tsoal~i~OO o:fth~L'!l ~;'i(;i~iO:!1\l[~~g~ of .C~ii (~) 51% ~fiQ!1.o·>o:xyget~~ ~rOOllI_.ct wilh cit. 2.9%fOOO"verodi stulj!'ig f:I1!aterb! {min]}] il,1d.ka:tcs tllilarr~bs.Ull1itW!Lt~ev€1sofill.dimllnil\'9.t~ oxidati.on ru:ew:n lilCJiJmx!. (ffg. 3.). WjJtBn a.I:tiLgh~y
l~roS§Ifk~w ox.j,::lJi~d .L-lcool:\o:l dJCtiv.a.~iw, hydro.xylatkUli.

a,OCi~Il1!lfl Qf iliseWOOll1 of '!i2,-O,2:OVN IUilI. <15m 1.5 s M r,o oilli!t~~pe:r,~hlr~ ~(50 Higiirt o/m ,em 'o/~', 1.2 eqUl~alen15(eq-J in (I\ON atl0.13 MJ Ie a ~(I[aJiCio:1iIof 41[;5 mol.iIl' 'o/Ill

~.• )1;:",81

i, :<""OA.~

4li.I~)

!93t.;.a)

!Ii

t
.i3j

o..~l .~= rO (*t-.~~! ~"l-'n".2:...

MO-

·ooc~ltti~d 11(C~,,*'ii!~~y"u ~ !lhe:)Q (""'f[oond! (~ntry

:ll~~T) .~'(~2)

H'

IOAQ

,,~1~~)l~
,~o}-ti!

OO{6f)

EI!:r~~)

'. oW o/~I~.. .kOH (0.5 !e:q)!Jill.), aJldsl!l'm~~ ~11 'C~ON «0.67 M). Mer ()f 4 (5 m'O!%) ,~~dl Ad]'! '(IU; 'equ~;v;) 1111,CH~CiN 100,05 M)is ad:Jedl. rd-· Ir~li!I~d:~' drc~sl!'il"d"
H)
IIlIiI,ilil, .ilI :!If(D'riIdl prntiorn

8). Alti~~i~S;hr-eal~F tha!i th,,~itern~iom~ g 01, H,A,a;!I!d AcQH ·fait 1.0 ~!1Cr·ease PXOOl!ct yve~ds.. 1\.."C'yc~,i!,!S lO:ri8()~>l!ledi :SOOJnltlg :lllal~aB Iuovi:des an e::lJoot~\iU Sl!~te~ fOli obtiljning ItI~gb yi(!lds~v~~~~ !lI,'1Jlabl!esubstrn'les~ for cX.!I:~nplll·. V IIlrlC .L~lm!leUnQI erivative was :nxycloo. .f:i'\!!~UIW'lS d W olbtail]<i! OOl%isolal~ yij~ldl .(]if·~ {-)-12 (c!U"t~ 8~ em~~!ex s~~lain:nlO~GCiY~es (l~e!~ cmHlI:irl In"lJ~tip~~~ C-!H centers. '\Vb sm.~.glnto tll!".resli" 3 gat!! wla.ether thle!'iii~lo. .sCl.{Jclivily ofoxklallim 'I'liitJm. c:llcclID,phiUc C9talyst4is .Eml!!i~uv·(l to dIG: electrmil!le cihVimn1lnL'lnl. of lihc 3" C-H bOlld (Fi;g .. 4A}, A s~ie$ of,cilii~l~dlrocitro!l~.nol deci¥.ui\!'~ wiere !liVah..!O!ted'l,';'~Hl 'el,c'CIII'Dnw:i~M!1!wing goou,ps (EJi,V"Gs)iflu er 11 posilio:ns ~(]Io one of

or

I~eactio.n mixNne ..

ditioUl ow H:.~Ol ~(II wi 0/0., :]1..2 eqllllw.) mlil (H3Ctf1lJ ,'01.:13: M);: ~th]rdi'ldcffii,t:iolll is th elil ,aOine in the same 11lIiI"lI!Irnefa~ .iill'lD<tal of 'ill5 m:olO</il, 4.r } ..5 e'Ii!IlI~V' A~OIii,."Ulld, 3:.6 iIl!i~lJiiv .of ,H4;O<:. 1~~~dll:lffl.~~llIll1liirlgl r •. . iirllm 1~IiiS~~OC'ti\li~!:!llildl(l·v{1oo~id:atkll:) w~r~ ObSl~~ied ~~.tra(le .alrrnOI!I!·lJts by ~lfht'!JMIR ::!~atysi:s ,of 'thE!' iIJ!'1t:li!j~

the t\l,I·O)0 C-H

e~I~n:ir:!li (Fig.

48) ..]I~ Sll'bll'htcs

IAf~'

H ...............

,«_)(_ ~

[~WG <~EWG< ~]
~'Jv.
II's.1ed I[RuiMiDte: $'!I'IIel'Clr ~1i'.51ili1~11Pm~I~l]r
~a~(29) ~3 ($S)

.1lI~

N~

~.,

IFig. ,4. (A) Re:actMtytnliii~'U11$ fOil wffidatn~riI~ cat.alyzed ~1i4 oos!edl 01lil1lllH! e~ectl'1~l'Ik5 o~ the IC-+! blCjfid. (8) Sy~~~ ~1!l!W():ifik: ll!'U~ oil! siit!e S!e1.ec~]viHtyiril' hiydroxyl,;IDOlliSOf m!!ltti1P11e: 3" C-HOOIll,oS wit~1 .4. Onlty smi1lU[lf!ilolllrnBof d~i(ll 1b.¥lil,r,od'l!lrn ~re ,()bser'!ledl (0' rnFr·~kuQ:alted ~liIrel'!-dim:ensional :5!trucrurl'!!' ItlftliJe ~Gli'liest potelittilil. lenergiY (ooformer of H-i2:3Wii1i1 mm~espDndin.g alikulgt~d~~~cbrost;rtiii: aib)mh:; dna rges I~W)(If 'lh~ :~~ C:-H bo~dcS, af ~J1ter'e$'t.~I))SelKflvt hydr'~v~ DOI1lI of ~:~~·23 (:-1 withl 4· bas:ed Illm s,b;lFk:: at ~ff~(:ts. IFof~t~d1:iliid OO!li!dlitio:i'!~ :S~~., lli:i~'. 3.

~H~X

Alipi1Mk (-HI OOnldli tl"loa:t: in@ 1000id~z@dI tof,OtfiI'rI

Iprodud ,Ul11i1i1d'iir.<litedifl

4 19\ X""Ok
20~ X= B[
I"I~
-

.313(3~ 043 (2.0)

wed1.

49 t21l'
·q6 (17),

29;11
2(l;ll

.,
6

HI ..

{!;

.R

HOJ ~I~..l.. ..R /~

a

2'1, PI = CH.J'
.22~A

5'2 ('~e,~
.56 (321'

~9~:'
;099;.1

= OCHa.

'UlilJassqlhem'lse mt.ed. i50~ yii!~s lue 0.'1 pum 1maJ'1lf IPf(i'l!LJI!;II iw1aIal:lI!lQfIlIiII!ElI ·frl1.r!1 '!Io~.worO!l ~!iWd .. 1l~~11!g !f!3!OOt!!.~C .a!"!l!_~.~ruo!'·~d~ ~I'! J9;~~ IIlI5iJlallidl 1I.1;1~"ol n 'r,e~OIB'llll'-Qlil'lll8~

en1ireroodl'ooi 1Iil~
mrxlLm u~ .1I1l1hon!:!e

r;;'Ac

AcOH,H2~ cmdit100s

cat.·4

8r~

REPORTS
11.,1I!J1Hl:lt!lm;1t

wid~

!!Q. G'J~lAAlic

bi~

,~lJilimo~<tr' mi'll~
;d

e
Mea~ 1IIIIleric
.;: H

,~HiO\.
(+)-2B

~t4,

tmriifiotns

S1MIda!'i1

we:Ji'e r'O:rIltled (enll)' ~I ,,~n ,!In oil~ cases eva'h,ml.oo, ) hyd]m;yla1ioll m,dl .:I and H~01: ooclun'ldlp:mF~rotrltiany arfhe 3<1(:.-,H !IDndOOliOOUic fromdle
[~:~iI!Qts;

l~ro1>l.yllW:ecll

ooijJ~ O~1t~

QiW

o
MeO~

HH

oat. 4 ,MOtl, HzO,\,_

~ar-d -

~00ns ~")~29 IlIIldl~'I:eCiI '0 Ha~. :, .( H

~Ii:>rt~

EWC~ {~iUri¢S, :2: 10 8),. ~-A~'4all1lOlfha~_ogM fUilctiOI'i<1,litt¢il ga'il'~ ~tioocgl lliu! i;Ls$fu~ site !l~I~tl:vities (cf:irCri~ 2 ~o 4), ol.ltdr.t~I~!W!'I wi!lld_m'Wi'~~g; f"~c~ol""lHll,es IreslJ!l~edi!i' eLl!,ce~l~l selenli",it~es fiJ!Ir lratliom li,yrlroxy:Lariorn. (murl.us ,:$ IIInd 6). Site !ro'loolillUnies of ;;>99:~wero (JJb.scrv~, w:hm~ !lti'Q;ii1gly clool:ron-wLuhdi1l.\\!i1ug ecwonyls w,~in~t:;iWd un lite Pl'l*ititl!~ ~1:!J{iv~ to

'n\ese
~_1\1

o~~~rU~¢ 3,<> C-~ixli!~d~

i~

{6I'!~lriesj <Rnd S).

re~ul~dcnl~~rnle (1il<J!1: C-HO'Xidlltil!'lr~ wilb 4 ~re~bjecllo decl.!~il'!!>C deactiv&tton 'Will:11 EWGsin Ihe fj m I~,posil.i:o:ns.

!+)-32

B
II,ere~ro!illc:
G. eortiluI1BltEl

\\l'e..I].C'.)ltiJ~'I,!\cstig8J~oo.wh.ctltcr·sitc g~!ecti!,f~tOC:s .of oll!idm:ioo. 'W[[h.lri!l~lky ClBl3Ilyst 4, sr'~ Si1n.sluve tQtl~~ s(,~[h~'L,'lI'l\,ir0l1n'ie:mt ·of tli.(l 3~ C-Hoond. W~·cWIO~ '1:0; C'.l'llln'!ine {-l-<lceta"'Y'":f)-~~lMtb<!!'lC,
ca'I. ,. ,AcOH,~ ~1iI

~MYS ,47%

,=~

..

-;»
f9C~

(+'):-34,

;:;(

23 Cfi~. 4D}. EroIergy lflli!ru~mi.;r.a(icmc.a~cuiiations WCIie 1Pe,r'roli'Jrned 011. (-},.,Z3 Wll'h, me of dCllS~t.y fuiH!~ioll~l tlu:lory (DFT) Jollow.cd by Ca:lC'l!ht31no~. oli' the !C.1ccO'Osl~::Il'ic atl:!111j.e parlillJ C~Sil"g(ls. .h~ I~h.(\lI.oWB.~~ poilmrllia.~ energy COI1fa!'!f!ler of{ -)-.2.3. the two 3Q C-H oorn;l~ ill th~ Y posi~ioDl!Q {heace~oo: grolUp (C- [ .and CoS)

Ji.cO~\ ~,
~~'

em. ,~

SlW'ldllta

,u'relhe least positive .md have vel:)' s!mi~::ir 9~m'lll:te cilarge.s;" :SlLlggestil~~ <I high :similarity il1l. tlt(';~reloCiron dC:lIsiti£:!! (f~g. 4(;l TlllUIS, ou'~y om dnlll basis oj[ lim c;leomrornic nlClors, CiI'l!lnvah~l~t ~e'\!d~ (iI,f i4E'ii.d:Mkl'll \'i,iPI!!!]d ~ Ipil1OOic~~ ,11 these ~il!e~ Bowevew. we Qbse"ed !J. stliOfl,!J, p!l'e'leul!l'loe to!' m;:idatim~ ;!.l!t the C"~, s;ile" i!II~o:sl I:iJlle~y OOc<!:iI!SC ~~ili 'is less s:rerioollyllliiLllldc!'ii:d site (Fig; 4D} '1I'hc: gel.ll.diIWCd1yl i!1iIi'OUP o;fd~c:

00!I'IdI1iol!s
,(+}jlJl~
1m!

~~i'I1

____...

,.. (+)-3il

mcJl'l"ll!

~x

jsopropyllL1l~]tillt ~~~cn'Cf1Th'~11iIIinlrnilzcd.SllnlClrtlill is orieUl.ted 8\>"3!y .from dIe 300lBru nmll3~ly to reH~lIe ~!'ilfa'{Qmb!~ M'ericirUcr.Ol.(:ti(m.Dt$ cong Ibm:K!li(y~l P:_iaoe:s the 3 C-H bond of C-8vroxhnOli~ dJle1!.l;le!a!~.egrolJ!ll; mali!Jig tl steri:caUy l<l

less aocc-ss:iibiJeHI ~e o:ddaru~'lim

the C·,I OOlld

~\- ;Ii "'1 1 __ IFig. 5. '[llJlnu~, modeii of !!ela:liwal~hatic

(...!,H bolild oxid:ail!iOI"IL~dllJj

-.~ 4 v~X·

~i

~~
1
~I

(Pig. 4e), '1ll{;fi~l'ffi\trl.'; d~Il'!OIM;lmled~ill,ulI. m:01J}011I~es where e--:HbomdSor mm~:lareh~lrcm.

':~~~.··.1·(J(r·.·- .. :" .....•....

'f:t' --" ' ~

'I,

rlbllSuni~ ~
alld

o:mt!oom'bJin

30 (-H blJmlrol[l~d I~m :5~ltU' li!utOl'lizama

and wiIh clt~ of C edI:ih'UllM ,ocrurs "lOCIL@i'lSltsh!n:a[y IliOO8rW 3X-H ~CI1~:W hnlil~ (*).",35. ,[lit) s,btt!:oo.!1l! of '~.)I.J', det!ermined byl!i.~rtLYi!I1Ii!IV5is. 1Nhe;Jj)H~16Wil1s,expo~dto !itand~l[d 1[lBtIctin:1iI cumlitions, 92:o/-llofttle~trrt1lilg lilliiate-ifatwas r,OC(I'iI'~di OO~~ of~r()llkd~ttiv;rti~ of·~ ,o(l~al1ld~rk ~llli~(IfI ,@ftl'le ~ropr,opy1! 3~ (-iH bQffla. ,m!) Cal~,boxyme·diireded lacmrii...mOfflo,ftetroh~rogjbbm!Uk aJmanatag (...,}·31 vi>aJ C~H de~
a:t:tl1e moot @Imroo~m o:dd\al:xm ro 'form larto:1iI1l ~)-3Biilil 5120/0 ~oIaterJ yield (re~ ,ooCie).fl~e ~trlJLOOJre.!> ail' (;)-37 and (",).,3:B Wiere deter!il11irne:dl by x-r:ay 'OliY~llogiiaiphic: Ilfilial,v.5is and ,illITe shO!i'lfn below. For w'bSltr-ates, vd.ihca:riboxylkadd dinN~llililg 'J1lfOl!PS[i,@'.. '(+~1~3aillilild (*)~:a:1m,AcOH a,ddi~w' 1{IIjU'om~dl for add"S!ilIils:iitl1i1i~stllbstrams D\i1~" 1~:+1-341 AG;CH~laddime WCiIS lm!ffi~~dl to ]0 rnIa[ % per arJdiffi 0 iii.

'(i'~~26 rerovered 1m,2;';%)lielc:!'fi1:!m the rl!N:lctOC!liL 'Willi ,[II) O'.Gdatioli! O((~ a,tiilile Ieast:$terii~~1y hTrnd~. Q~ d!~n-:I'kh, IliIiletilylene sUe. Unoxidimdl[":}'29 was I~~rd J11 ~~Ill~d;l bmlthel~ttioo" ~!I!~ JdWdoob dl~ctOO·:rolihri:! ~riC-ll[iflh~oo~~~3!;> C-Hsifte: t¥~!.l O ffiree(1!r~i:: ~B)II1,redmb'lyse'r~ alii!hatic (41 l!ioodlloxidatiJ:m wi1I1l 4 m lliIa1iurnll,.oowm am~ th~ilr Uoo_EN1

lfIi1.rprodUct

'flr'!:! indicated

in, llied. 'ill OIllldMioo ~wl'5l~feJ'EIltil:lUyat

4. AIi:~:aiL (~l bmrls:thifl.are

the nooiSl: lem,oo'fith e

TlteL~lterpila-y be(\'!,!@C!~elec~rmu:ic .uK!. ~ecic raciiQ!~tn d~~wnining dle se~eclivhies ofC-:.H (1""Jdatoons l>':ilh " was IillUillhcr it~~lstlrlu:ed in it s:l;u:dy air rnuctllylrzsi.u:r:s frig, :SA), HIe.xallO~ {+).2;6 WllI..'l hl.y(ID.x;-;riIatoo.by 4 <'Ild H~O~ pl\l'dO& Ili'mroly at IhL': 3,,0 e-:Il ;Silfl 1~(l'l'Iilfi]lfcl~ a:!l:·~f M. :~I1.

h<'ll!lclle rOJ' sel~I['ii'it)',

prosmli:, SlI\nC$can ~:fil)vi(te It see-

5iity~·c~@iw_tig!~, (+)-2:7 as ~l1em~r

[)!tw;h.!;~t

ro Se!leai,~' Qlricla,tiorl,a~ 4 w-i1hSliftaU 3 I'I1dioouie: ~t4 ~

am.

Wid] methyl!k'~Qnll:: (-)-~~<lS the:~li.nQlir j:l,!'lOd.llIci (Pil,g. 5A), 1:,111.5otilb;:onlle was p.redicted Olil ~iIlIe b3S~ of' e:tClC'iil'\)l1ItC c-:I'I'ecis..[lilcl:e:f!Si,ng the sil~ric bulkru'(DllIlld tI~i~slltl b'y introdud,ng :11. ~oomd IIl~l'h,yl ~ulDst'UJffijent l.~~hfShtL'l f.}~9 i ~v~~ ih¢ ~eiiv1!Y .im~~1i)I11S itl fllrmaiiolil of m~yl keoone (+)-31 as tl'lie f:I~j:m' product The 2Q C-H bond 6x:idal.!oo 'by 4i!!lso, oocurred

ai, tbel1ilO~, d!ectrol~"ridh,leasl, s:terictl'lily h~llderodJ sit>e:..This ~liPG~rn1ernt show,s dlat :stccic; ail1l:hctil:eai1.ov~md(l c:loolronio c:ffOOIi.'!in, Siiw:

REPORTS
~el~tiYiti~
~jYle ~m~ly:s!.\!1f~~ bW<l:d '.i'1!!b5tr.:!,t~ ~oope tl;I 1I'<!lld ~~ie'j ~Iim~(Joxi4a'ior!<lt 2° C..rij sites ~~]g1YQflernw wi,t1~ acltfLeveI"4S0-!ike ~~lm'~ng enzyme ~el,ectl:v;"
\~1j)!ij

9fQXioo.ti(l~

selectivities simi~arlo those ollltLililOO aOO¥e for 3'0 C-H si~i!S. 011 11m:Iba::;Lqof !be knQwnrole of CMbo1(.~ )'laJ~~ a,;;;: ligand5lbr 11G1'ii~inL') imm ooiupl~~ iilHd die b~~f!cil'i~ ml~ o:fa<:$ti~ acid 'O\!ljh.¢~l!a~
POfS:!'li.dat~ Oa1'll,>1; c:amO;l!~ ,1i'!(egrlJ~p .o:n. Itla,e sub<srurortecould be used to dir,ool lite si~eofe-:,H O'x:id8i~ii:m (28). [llIS~p~ 1Ji!>OI:t or ll~is ~~ypod}~s" ~'le:x.ath'ilieacid (+)-32 fum~!1II~oo m~.ly l~llilefBv(}-rl1('liljnba:redrin~lacto:n£: ~ytic

ities is rermllrbbl!e,. 'iVe c'xpec~ 11'lm~ 4 w-illfind \\r;idcs;pr,('mcl;us'e~or o:x:idati.ve 1Il1odl fic;at~o~H, 10 Ihe (lQm WOOlums of nall.illlroljfro(ll.l.Cts and
pl.t\tr:iJYilil.¢~ijtLC3!l~.

5. Ii'. I'Itllll.~r', C. Firll'lt, (~m! t&m lOa:, 290i~ (2CCl3), :!ilj,ti re:rilli'!I1tilN!S ~hoI!ri!!i:fl. 6\, H. M. L.. Diwie~, lit ~, ~I,B~klMtl~.Ch~ •. IteKi.ui, 28&1 ~:2,003). (i!1dl re!liPl~e~ U~reil"!, 7. ~.I. 'C!!l!/E.'llt A. Y~~!A'!:!I. N. A. L!lbe!!~. ,m.c, W~~'. ~. a it. I- Fr~luill,mrr!!!r, lit ,c. While,}: Am. .the/ft Soc_ 12~:. 121.'i (20011,.i!I Ilml r@j'ei\!!Dll!~ Ih"!Hii,fi. 9. It'.• A.. W1:!fl!ll1~" M,. ti:. Hl'Ilfl.lk~ A,. V, W,.I!t!i\iW1l~ 01(1, imt. :][0., S;, l.e.~,r'. L, f!iKh~, I. Am. (km. S"O!::", 1~4••:iiil9iJ (2'00:2). )\!! etbere~l (-iii ~!!j!'lio~ \~~_h,,i!J '~~!I1lp!e~
'/W5ieol!l; ,CJi!ei!1'l, JiI~

.&t45. a~1!7'(~IOQ6l.

~,tivilyo.r"j'iire

n~ l~~ghsen~ilij.\filY.or~!al.~ ,4 to ~r:erie ,eft«:l<;i8f!.!!~dler iIluHilt~loo i!ld~e: <ltle'!ilPIie'd

oxidatl;vo:n of {-}a.-Cli~~y;djropicro~~!'d!l'~!'I, 36 {!fig" SB}. .A.I"! Qiflh~ C-:H ~:llIdS Q:1lI th~h:~ghly m;rgern31Icd. oo:~are CI,e1.Hj',Q:I:'ICcalAy dca:m:iV:3!lm. IOw8.iid oxkl'i!ltiml. TIu:ls on d~(i basiS of eliec· It-{ll'li\:~f«;to~ :"~(m~)1!llli'; 3,~ C-H tI·Ot~d(!If Illfili1; '~ooycHe is<npmp:!,1 ~lOivet:l 81~cu;!rd l!!!'l'de~o ~.

:r, 71) '[200&).

:n.
][2,.

(+)-3'Oil~ l00'!Oisola:~ :yiLliklt wl]~~~ o!(idlli1~:iOi!l of ihe~ltl,!!Q'!iI.~ !lle:nh)l'~ ~~t~!' +»-:J:'9i S<l!\lC {
]k!i1IOHC {+}.. ,]a~ dli:l lIillOlfjQf prodl!lCl 3 fP~, SA~.l'~e 'Iooninal cru:baiocylicacid m'Qielyin, (+),3.2. OVCUiI"Lrles IlI:e ~reviolUSly neted Sl.eric :r!le~yl

H_ ,M_ '!.. I[).aioii~.!!, :l(_l)a~. 1~"5, ~g!l!l. ./Im. ·Chem. Silb J :ru211, 2A,B5 (200:6). flj, EiI~rn'iDlilfi, J, Dill sal:!;. J ANI, tlrtm._ Soc, 125:, Tl.!H1ii

~1ii:~~~l ~,~I!'.!ii~

~. $i~l!.

loctive oxicllllicm with 4,1f.laOz. How,ev:c.r.lreaJtin~ r(-};J,6'lulder stmtw:d hydroxyblkm OO~dlUI,iru1S res:uitlie.din ~'''2% r'OOi)VierOO slM'inin:gma:mr.ilml.
E)i3m:U~.mion oili' all, .~.·rny i>~.enlm Ili'CVcals d~m.

:n.

(:UJ03J. R, Br~~lo",~ eI Qi,. ). Am OIeJrl. 5«, g,S, ~251.

(j,'~{~:~,

c:FroclSand d:imcts:hydroxylation (0 Ihc !ibideM, 3° she. Atl.ll0llgh 8. 'lmiq ue aspect {If alip~'ulitic
C-H o)t~.<i!~i"'~~il;p~ b:y 4 iL'i: 'Ul;11IilJcy d'o 1iI0l

'roQjyi!'le a diwecti'~~ l;lifiOil!!p fOr high ~k'1:l.ivi~i,C8, IliIlle01Jbi i:ty 1!(lI~sed~is;errcc~;pmvid!es<l U~lrda:nd l I;lO'1i.lef:rtl~ all!CiJ.c'for S!e~ce~ivil:y. Pood:ict0Jblc I~ ~cl'llcth'ityin fC"i~IH)nsc2tD~.~1 I~h,ree.SI.Ic:lI. modes ahclcm:il,'hyba.qpoov,OIl '(lluivc in IPriorm(nl!.l~ Ca:lalyzoo. aHphaJt~c C-H ,o::ddaluons.
'IDl~y;:j;II!!!L;lOf

dl.G'i!!Cpropy~ molcly,irn. «d'cr lO8iVO[t! severo I,I!nfuV'Qrotl:l~e~ri~ hU~c~i{)ilillj i (irierU.~~wlU~~ .. ~ ~m-dimillltllilylgrol!!p p~j oc~!l~ 1IWa:yf:fol~] O!~ ril;~,symcnl (P~g..SI3)'.'fI~isoonrm"l1"fi;o:t~mienls dn.c: iSQPropy~ . .30 c...:.H bond IlIlJdemealh ~c ll'in~ sud ~11.del'!i it ·.i:n::tene;ssi,bleto 4.. TIle dC'm:0I1· :SDra~cd.g~:abiUty of a.dXlt1iS€'ly fi.m.cti:a1il9li~OOllflln.·
~~

114, S;, DiI~, C I). II'It<I!'I'itt!:. It H. Cf~'llI!r'e(: G, W. Bnldl;jg,. S(IelKe:U'-:, 194~ QOO~l ]5 •. 1. JI!. b.!liIll<~W, ~!E.Ber~\l,I, lV!i!Wlif 411. 5'01 t!Q(2), ~IlI!i11 I r~r:l1trl1lit~ :li6, Il iii. II:r,~~)', l 1Ll1l1I!r:rlt lAm .. (Jle-m Stit.~:21'. :liS}9l

t'*-e~I.

(2IOO5). ,MlJrr.!ll". j;l, ~1!~ar,i!iJlaiffi..L ,M.~I'IaIfl../ •. Am. (r:-ttlt Sot. j]JO!9J, 2:4 iQ (I99'6), la., H. ~, Kolll.l M,. :5. Y<inN1eLi!J\!ernllle, K. B. ilmrpl.t!ol;, !(h~.ll. JIil:e:!l,. '94.2483 (l'~I\'!·). ~'.ll !f,!;I. Sh<!;rp~~j;,re.llWietiror;r 5>(1. 4235 tl:~4)' :2(1,;1;. !illiI,S, r!t, ~, q~ .i9'i(lmimei'i" O~li(l-Ji,5 fa~.j~' byif"r.m!;'~mt! J\'!!!ilM~Ei\I!'WI~s,. I~ JMu II1~F; iE:d_ [!lrIpeml 8re:~'$\ UiIl'l!!l1:Kfl, .MOO), ViI~, 269. 2::1. fM til!! rlr.~t !l!~1I1!ll!!! ~r i! InMIli!!'Ir'I~ ~f!!Iil' 'fl~l ...~t '~iIl100:!tr,lI!1!N! to, J(-I1lto1t :~Mn~O~PftJ;Ii!: ~Jlk~IIII1'

:li?

m,~

th~~1!liphMt~ C-Hoxicluv(m

m~ p:i'O\1iL1C1 dmi.vau.vt'l to lihis Qii'I:[cl!llliOOl.:roaCillh:1I1 ('0 '!!!!1id~~(Ji~ tI'I.~ ro!1~a!bb!y mild nMI!U\'l

c~ne-ge:

roacliofl foc~~s!a.ge .sYl~!lresi~;~ on :hQ'W f,redicli.\'C the c~ootron!c, {ijooric, and CllrOO!l1:yl<ll(& diroctimlg medes of ~kiClI:iviruy are in 'OOllilp~C.1I!. rnoliem.l.1ar soU:inrgs.. In ,on:im' !~Ocwlu:llJte:tlliIis ql!l.'e;s.. I~imru. \\IIe ~'i{an'lli[loo 111,~ C- Hoxirn!ali,o:n OF ;Emlem] Iml1iIill,llt.1!lp((ldlllC~i! nd thcir &rivaliv.e!ii.'1:vil.h a ".A'nltm;'!I;,l:;i<HJ O(m1IxUIII'b!1 (+)-afl~rl1iNiiJfl'in, .34 di!lpllilys five 31;1 C~ Mm <uo!1lg,ilS '!etrn.C}lCli"c
2

of t111i~ !~(\Urodl.
A l]lIOWerfula.pp:l:rcatim~ of 4-<call1lymd Ivy:. droxylatioll!> is I~O 'GlTcd caroox.ylm.~G"dLroctodl,
dias~e~,j£cti'!J{lloc.w!n.izaljmilS;M 2°' C-ti :!5~iIGS,. 'l!,\~ ebose ~o tolValtl!3lE Ihfu! awUM~ion will!ln. telm· hydm,cjb.~.l ..~.ni\c ,add analog, {+)-0.3'1 (f"ig. :5B),

,~m.Soc n9" 'S9&4 u 9[l'1l. ,2, ~t~!Jr,~t. r~II"Jr1,!t1 ~r(l!'1tme~} t(l!'!l!!l>;:~ OIIl,Lliill!, <!~ ,~I;li!i!i~1!!l reOiWrity, ~~ if. O~I](),. S. II:Ii\. '5:.0ltW, Y. !'l,i~hri~ i"fi:i1MJl 50(': Om'ii!loll rttrnS_ l'i1'~1 • .35·,fl

1~~<rl1Qn,

see C. IKim.. t:, {n~l1,l. Kim, t, Que ]'1.,

J. Aim..

1.1~ecwboxJ~ate m.QJcly of (+)-37

Ill!!)'

direO"l

(1~~7l 2':J.
j( (II@II'II

l QIJ!! ,II., C/JI!.!i'I.(;~JfJRI,wt 199'9', 1.n:!i

skclewml

:SC~OO1livil:y ~5SUG

posed in ~nll:is:ruDSIl111!e.. a cheno~~c(lniv:iJny daaUcrngeis; [p1ML'tIlifn, lite famn of a ~lli~mi\'--een.dqJM!)(id6 fl'lOiely ltf1{MMll. ·be. prone to Ito f'~(Ii}J.tlooia!~d~'iI~S~ (;2'9").. On dl¢~;S: .of I~beseieClivily mle:!>oo.tiincCl .ool!{e,we ~rOOi(liW I~~<li~ Ihe ek!cl:ron·ridl ~lndslreri~UYll!tef}c'1!1I.1~ beired 3,0 C-H boud ,11.]: C~IO would! ooa.oddlizecl ~'ruffreild8ny.'fb(l nmmruning 3~ C--M OO1illlls are i~.fm 0: Mdt'or ~ position :DO C!lcetnm·mlhdra~j1l'lg ester and ,oodb;pefl)'"xid~ l:oo~elieg. We W!.llrogrnlifiedlo~nd lb,,1dl¢ se~~v~'Y n!I,~rOrO"Xi&~~l;~" wi~h 4 d~v~1o~dlQn rela1ivcly sinlpl'e

{F~l!ll. SBJ ]1] o_d'dW.Q!t

HI

(he

Si~.l~

~l'oo~i~~rellttlOiucl)l.We

flve1"~~~lTIl))erodi!llg ~~c!O!'I!iizab!iJrrI..8:Iy410 ene of r l [oW' G-H bends, Om the ~ru;fui: ,ozy~~· logJ'fl.phk: ru.\fl~y$isof (+Fl7. we proi1iCtlXI d~a~ hydroxy.~ati.m~wOllkl. OOOI!lt' s~lecl1i.'!I\e~ya!ldle ~. a 5 2"' C-Hoon.d on '!1m D"ring thal ~sdooe:fj~,Il) Iffim

or "'.my

(1~9), 24 •. M. C. Whitt, ~. G•. DlIl~~. E. ~. j:a.aJb:!en\ StJ(, lI:23:, 1:t:~4 (~OOfl,

J. Am.

(jIl~iJI',

~5,.

\~T:e

gra~~i'oo.I~O find

d~al hydroxylation w~~~4 .;lind H~()2 fUf!lts1JOO fl1o'C·'l1leIJdbe!led rill'lg la~l"Om;: (+H18 <liSa sh~e dlasteror.181l!Crin:52.% W.ated, yield (rec)·.:kd O:UlOC).
Wkilllhe
salli~ ~~

rnmly5'l3

a:liinroOOl(+}j8

A. I. p, Whfl~. 1ft0W9,CfIMI'. 4~, H~2 ('20'01). ,6\ M~·teP<lI~~d 11'!f!eI!Ii~ ~I\!:' ~,v"i~b:I~.,.t .S"dffice Oll1i~. ~7" It 1)1. EIii~II.1-t JlriHlte!- • .MA1..5tt 1- J. W',.M.aJgLliOlll, J 11m.. '(h.lm~~_ H:S" '~l6!l (19'H)' 2:8•. ~. Y. 1i!!!IUlo'.<J', ~,. ,~". ~Ipp!l rd, t~m. ti:~~,.illi, ~B1 l (::WM~. 2:9,. J. :;!:I~I\I,Ill, GIIII, J, DI.i, y,. Zhlil·~ IDo. ~~ Ter;m~r1ron len, ,43, 4SH '[200(2).

J. EiIlglanll.. 6, .~I,P..1E:liu~!1i~ NI, Ra'ba~.

iI~ ol'lly 26% iso:IMo\XIyiG;lid,Lhis lia.rg(Sl d.iITerml.OO ~fl yicldswiiih. t:alalyst 4 vcrs-u..>iJ hMpro\l11:l~ ge:nt'la& wilh ~I CQlTIp:l~~!.!!b.~es ~~ni!led. :hiflpQ!1al~l$-y" ol'li·thli1Jl!~ ofd1e c(J(~~icspondh1S gn'l.'!1JilyI'~f ·o:f37 v.1hkih, is (+).,3:S~ GiV()fl dl(l; 1Pru.dk:lab~Jl ooacti'!,!'ity 8!U1(] bro.'lel OO(),pa dl!i!litl:}jfJsu'ittoo.wl.wis sllJidy, w~ aJ'ilieill3l~ Ui!@titlJs ~~~1~r.t1;l!1~1l<i"tk; Qxid!!liQ!ll!'eadtQ!l!; i C-H Iil!!i!d' Q!ihe;m U~!t,wmf~f!d.<!!111e!lmny @.Iter ~!e lMtys in 'I!.~'lic'hcom:plel'l, Inol!;ic1!l~es and 111jlMlm·
!OOl'J:~ica~s ~}'ind:K:sb.loo~ndn,e ~3'lbo:ratory, ,al'iC
IRll,f'ell!:flGl!'liand NGtli'j t:. (. Nioolaoll.. E,~, $or!lrn~II, .CJ'mskliiIiIfo.rar ~,ri~ Mill, N!i:w ¥Drk; 1199;M'" ~. J. IFr~lm,liI(!,frer, ,D.l\. B.i!dllOVl:M!iI., n.\ C. ~Ili!i~. ~~!;'rJ. {, ?~3(~OOS}, It. w., H!Mrm~I:I!iI. Synll'j!!:lJs 3:5,;11 (ZOO~. .Il 'F:,. lLlid; r!.t. S. S1li'lIfD~d', l.1!trnhM't'J!)t;I, fI,t .2~,39 (21006). !!1M F!!h:!I"@OO@,~ UW!!FI!!In.

30\

s:,~l!l1)!'!,rQr ~~r~)'(~tJ!Ul1lg~~~i( i!~()~~,. ~,A. 16igi! ~,~~I[I_ J. (~·'IIlUl!fJ(:ii!!CHI\i!I ~tJ~ ~~rI~m!:l~ IH'lXe[!IiJr~'.
,alili!l:5, IE.Hl.i!IiI'lE!l: an,tiI (,
S,

w~gratefuVllI'

"~kn~~di.li~].

EI<! IJ!!I!,,! f,~r (WI 0lu.III,.;i(j'~!Il.

lteg~n5 for a gifto~

H2I~<!rdi

(S.:s)"~~,~IJ,ii!i'Jrulnlllin,~ ,~rtul'!!'.,.IIlS.,'C,.fI;, III ..

SUbSll~liCS QQ~~dIbe ex~eliLded ~o !!MsOOH[p~elll

!~Hl.~lYml IProou;ct (+N (}~JHy~:oxym:te r:niS\i,niirD, 3~ wa.~gpmrn'lltOO as !tiI~.e m~jO;1prodl!lmirn, 34% y.ic!d (4 [ %:P..im, F~ :5;8:).By rocyclinglbUil v.all!ll~M¢-sta:I1I.'ifngll!!l3.Hlllal ~lIiIrol'~gllil~Thl,i'l 'i'lact.t(JI!'~ f Ilwki@, we Qb'!mliledl diru;~er"oo!!l~~"tc~n, pl!r~ (+)-3Zi!!1S4%iSQ'I~ted, yield. Whh d~e~~!ne ~iroWiQO'l. .c;,,";Jillllyst3 <l ft"l.looet;!, {+).,3:6: i~ 01;11.y :2J%iso~al~.cd. yLckLlnt'CI:~es(i .. gly, (+)-34 ~'ms ~:revi.ooSity beef~1 ~fiZ.yI.'L'na:I~,Coqny '!rmsfonned to (+)~5: ~n]4'fl'!~yial,d W~.I.bmicr{ilbfulc!Jl,~H~()f Ct~I.~},;,,!gkCi.I.~r.efl~ ,rx:Mmitli.a (29) C8!~l'l~ysl! 4 gives bi~'t!e;f yielcils d~_Q tile e!ll)tyn~~.ic reacttm~ 'Wi~h su'bsll!lnlia~:ly s1mrler fea!l)tiol1li mes (~ilillw )O"""llU" reacti.mn;. nlilru$ 4 days) !lnd a l~rold:
~ighet
'IIQIil'IUe 'IDllf:

[n.loos.~y !~"Ve~ ~l1ig UlOlteri",~,~~d m~"'llJl!eS101' 1fIdcf:i!lled, OJdd9.tL'(l.l~l~> u UOIJ.e: of

~I~cli

llInI!i'Il~til' !!lr,~dllimli!! ~~lIlI~1lt'~oll'l,pl~ll.rl!Jll dU!tL'o~l WQit~;lll N,C.'!!'. iI~ ti'nr,liil), m Ilm'OO'r~ <11: Lirb,ma· (h"ii~iI(gn. !We <l1"IIl '!If.iil!lldili til' lille .AlP. :s.:IOJH
1101.!!'!!!iI!!,1iiI!lI'l"U~ Qro'lme ~J!J~ He!'!!,,! I)r'~i"'~ f,~ull~tiOf!, I ,a,lId IlliIi 'University QIIIIJ~ncii5 k<rlif!OIl];d~1s!J,pJl<!rt ,~t.C.W ili it 2(101 !.ill~ 'Gr<!~tee:irnI~rd rfliipreflt S"'lI'plellier:rt~!Y ,~~~~U~r~pl1i!; '~~~~r ~i!ol~ p.;!~r @fI ~. ,~~"'~!'!~1tI {r~m the! C~rnIruimge or-:IaiIUli9rapin~[ !Ji:lUJ Ollifli! v,i.~ WWIH:ak:,cam,aC!Il'kId9L9.J'B!lII!IeSltci~mn, '~ii~tilI!I ~~~1I1'1' i . mO\!:, Cl(OC.-6~:lL9.~B 4,c:mC'·6,619li~, fj}J 1'1lI(-j.;Ui~ _

CIDC·66.1J93:.q· ~r 't+)·:n. ,al\l!ll ~CrlC·661936 ~Dr~+).318~ I SUIlI'I)!,,,,ti!"!gI On'heM!!!lt'l!rial

1.
2. 3-

.~m'r,!l1k!Di!!r::rruI:M!lWmlillll!nIJtuW3,11ll1s.1l51f:1\~.3mCJ) Ma!en.al~ .~~ M!!tli!ll~s

fl!), Sll T!~bl!!S51 to' S~

~re,elllC-e~: 31. JIJ 111' 2:llill7~ aO:!!!p!.!!ol :l OOI(lil>!!r .2J)[hi!' l'llIl.12~dftil~!!.:n~~i)1,!

(IIr.OlJ]S .M),

'lIu:lYl!I.gb:@t1t (tl0:l3 M \I'~lIS :!Ibi~i'~y oili':1i stliit'iJple, Si:n~U :~\:)tc-

~,

zoo~

REPORTS

4DI Viisualiiza'l,ion of Tr'ans,ltiiolnal Structure:s in Ph8:S,'B~ Transformatiens Iby IE111'B',ctIFo'n D i'H:raetio n

i(,o;mp'fex ~relTl'll> [Ill mmclelllsed pfiai!l'Se5 in;'!lD!l~ iii Irmu~~tidlhrten8l:Dnal fne~gy IilIlUj~~,]pe,r ,Cillldlknowledg;e af tr:anlitJIoo'O!1 !ltrt!lmtires alild ~pa~atiOIf1 'Cll,T lll1lf'3CilII.e!lr!Or atomic DilO'Ii',Nlilelllt5 'i~clliitkall. to m Il!Ind~rst'.af1lding tliieir ~rolillical. lrie'havior. Her,e" we l'ejmrt. lJ~lng f'(llJ'-dimen5ioml (41[)~rellililtn~~n~dl ~~ct!'!l::in di~ri!io1ldl)",m~vi';l,!Il1!tliza,ti(l11l Ol~'tr,gns;ftio,na~s;tr'~ICU!!lie'Srroillil th~inirigl !iIlOl1odillh; tl;l,Ih~ fiirniil, tetJ.cJig;CINillilba:se:in 10000~.tltrll'l~'I!',"'l!!adiuml dio~Id~;the di!an~E: M!iS·~nililit!ld bya 11fI~lr·h'!'ftaredl e~dt,moo,. By r,eve-atllil!jJi 'Ii!!' ~ameHilIilQrall, behli,'II1Of ~1IXIIirI al~ omE!l"II'ed 'Bragg dlffratil!l:on~~1iI 310. ~nefeilil1k1,secondll~IiI1"iy vlllilild'lI!lIlll-VimtlidiuliTIIllIond dilil,tiool, lie ,dl~lill!iffilllem o.f ,ilIDmI~i'llpmSl«ond!Sj' <lind the'S'OOilll~wa¥e shffalrr IlII1Iotioo on Ihu:m~redll Oifplmselioncs :wer,e m'eSlllllved,elu~iGatin!9 the
nue of' 'th.e strootural p~~al1d ~e liIonoonce.rted mie!;hallifiSma~'~~etliarn~'Orm.a1lioo.
:ar!l'lcl U~~r!'" !1].:otig!L~1~ ~~~,s~cl~

~l\lOll~Vg

ing ,mlil, I(]Dtio~C»yl1lillnk;s :by ullr~flllSt)l,..rny n~ so:rrplio.n (3), and dHrrnmi'Ol~ (4-,7) ,1liGldiek'Oimm, diJifmctOClliJ(8- HJ). In mil': laboratmy. I!Il1nllJ~(llcc~ ~rI !'I'!Ii¢iiO~py rUEh4J) illid i'itl't.~fagtdJi lfiFaeliom (.U) ha'i,1l~ liOOt'ith~ lli~llli'iod~ ofdlg~cefu:1" :iltii,idJL~ ofn1o!lX:ui~(lt ali,dpl:uL~lta!U-s:ilioln'~ (J 2-1&)' r.n I.'he OO!"de1.~pll!<lSe,IJi'e use of the i1lf'i:erg}'
18n&eapec<meG~ .hMIlOOe.n;~ly been, tBioorel.icaUy adlnressoo. (17, .J 8)1 :fOll' IIrtSf'Oi'f:i'l8uoilS i,I'I'\!IO~viI1g two 11iI~kli'fnoo}'ii1r:11i'il~ca~lySlBhl\il: ~O;j1figwati(u"-!;, as: mso~:id-Bolid 1tt'aI'b~itulJl'ih~tl1le~ ,:;'t!i'O: l,,'IOda.."'-~Iilf'

dis~~,

~~1i.l11iV~~!'1ig!b I;I.~. the ~c~l~Qf ®m.k: as d.erllg~lfJied l!ll tlte mdlecso:hneh-

d~i.pt!:O!~!t UIo-seti~Minvoke fum! Ow moti~!'1 o:f lilea:toms i!'l d'leu!'lil oen. and ~aMnhcl!oWtice o.~<I!liZOlitiool £lind, i!'J1O!lelhat deal wi~IDl.ltle~otl~ ~ arramgCltltmt On~,1ela~~ioo i~clllldil~gdlC'd~~ace,.. IlH:t1I: of lJitlH~e~1 alruns."1li'e 'liI:nc !>c1!I.~('lS 2Ild, l\attire of $Ilrumilrell dkUtln: 1l'1.'~V3Hdiry ·of dm 1J1L:M)~i~[ <!ItJJ!l~~'IiI <lud\vhiU ;9~r'{lN,inraatii(un. ..
Phf!iJc.a1. Sl!:ila~'i' (~n~1!'1 UJltil'ar'il~t. ~ Q@'nt:e ililld' 1f,~dmol· lor ~!il)!. f.!rIlliimf I!.IOO:i Nil'/il'j lLaiborattJflI' 'Dr Chemi,,'l'l Pilirt5ks" wlir'lif!li~ lil~tiM~ol 'T'~[!lologll. f,a~~'n<!1 CJ\ U1ZS,
ald1llr'i!':!5i~d [··rn .. j~'

'W·'

. . . her! IDulllmrn!l<ltic'ns ,of ~~Uefi!~vol \Ie ..........•..........•..... m<l!!.~J.',u.on ... ,,_1!;S :h~.o,O:.·In!,l~ mloou~ .. n ..' _ iitnrlCltlil'CS 0:, in cOllc\:ln!>Cidi! phases. I.m,.

trn!L'JfoVl'm}.-

fioD!s~!lvO~VC en ene~y~~!l{L'lCl!pe desccilboo '~ IrnDlsilli.o!l S!m~El:ncillfansient inl!el1l1;Jedime:> (.1)•

audO:Il~.y \\lhclJ: lIl,lC til~)!} sca~L'lof (iI:bos~uvmiOl~is ~~ejlidJYua:mlc!l1 bcl1.o"i.lli'iocreq'Ulf:'C!>he, t US;/t Irn'ansitttoOO!l strucl!l!lr:cs ap~,!II~ can such spreBrul 00 stud:icdl (1). fOi "'!i,ll, ~hllfl1' t!lrrti~pornlflde'JlI(;1! ~I~ooldl be wl~l~.spallal. and 'ill:nlpoml~oll~tiOil ()ifdH~a.I.'On~~ dJmcl p:robiJll!l;, Ihe' rad1iati(H~, or p3Irlc1~ used nltili~ 2!'rl'relil@(OI'lIi~.@flu
dL"ii'S,Ulltdil:tg

d,miGf11,~ilil3uolQ of aemal

IFii'!II.,:l!...(ry~!tal. stmL!lI~va~i!IIdium ,dlio;:jlli@' iIlfllftSie5amdl O~ rwdl Biragg djlrffaaOOll. I(A)! Clj!!lital ~tmcturte of th~ I'IIIOliUl,..
~1!I.i!!~a~

dink.. l~w~OOm~~fii!bH1!
Iph:a.5e Heft) and tiHl I~h!a,se (rigIWit). 'Vai!lad~ijml ilrttJ.lilllS arE! m,pmdl illl Imdl a!nd mY!l:~I:!J,awllM, in a Il~~Iht~r (elliot SeCil!!.!lse:of <lis,~IliI.etry-blie'<!k'illlg psirllilglor V<I,IiIi!ld:il!lm ,atom~,

.".

bm

t~~,~., h.-tem Pf)!~ o1l.t.ure h~9

filii-

-~.~i.,;-

'Md_.d ti!ilefS),.m~ aiJ(isdef~

111l1il:iii:lnsch.:lIIiIge. Moo

0:-

dv,k ~or'dili1!ltes. .a'!:ld aoces· ,glt"il: 1!!!:;~If! the' p.al~r, ~.

to E) Ty'Pica'i ,difha~m I~aijerns; oIb~ii'lJed I¥ IJl~

t;l'alil,st@h~wofl'~~.:ilklg; ... I~ap~vlJf dlUferelilt 'ay:5tll f

sllriaoes ami dj,fi''fn:!n.tzOIIIe

QJ~~s.:1i ts the

I~ab@lsl

lliTIIilj~.· dir,ootJiOru .and ~~ ~ls lie ela:tro!l drecticlIll (moo axi~jl.A!U. B~~!1!!is,potS ,c.ailil : I~!!idlmtifiied .&s.1he'fIrlO:1iI0,.. d~filk ~UI!I(I:I!I r~ '(yeUow

SlIldgll)~ !ilCW~

REPORTS
@re<Jippro~~fQrdl~
~y~

~t~cmil ,cxciMml f11l1~IOO wms ~ to R4 dkIU'~, m~fjiJgb l(I mive the p'lla:se imlliSi!l!ioll v.';lh, a :s;iillgle Pni~.~~.Withun.tll@ i:lj(p~ciin~rrl13I.~P.i~liuon ~~od of ~ ~ns. litl~c.ySll.'it h~'ldI at molEI 001tlP~~ flJli!ly :~~O''II\~ 00 IUnJ~1h~ili,a.~ :!ilanOl::lilic ~ihase.. Thill: recovery was con'~fn1ed byob:ill.'t\~h;;.gnG dil!!nge il~ liIlIeclliffiira.cli.olli lPi1llliC1l'lilS whedll::r' iro«lrded. at ~i"l,!'e dcl.ayume (an eWoctive ~.~fir;'~ d!eliay) or widlQUI.t d~lll~X!t::il'3lio:n.'Whe OihservOO ehsn:gcs by (~~c;talno~, O~~fL'!;riQ~I'l';"'~l~ tll¢llolt~~ill\ri!l!lTl d1n.t!l1ic.~wit~lcl!;r! c~a$!'nribwl:io!'1s fWJf!l s!Oi1lie !teating. We c'hecJ;.,ed Ibr possil)[e effeo!s of surrn~ sYI'III:Iflli!t&yis, ~Co1:li3goI18fl. {21'). Titil(;: SAruCJJi!lre9Ud pat(mtilal ,eimngcM ,ail8Jrge lneap,plng on ~il1~dif~ 3XCS.'i\llc:re c!Xlll'vn:incd em 11iI1£re:Ir.n.o,sOOOlOO, ru IJUMlQ. loog..rangc:: (Dr:G£'r f Ollr.' vl!I!nad~mn dim:::ioo! silrugle o frnCi~[On dllLlring dm 1il':91:l s iilian from i1I~t1~:or I~O b';ooond time iiCliile. The d~~·"H1inC:iJlsiO\Jil:[l {3D' I1H:.mll pll3-~~ sueh ~iTo~~s we:ro found, as. ,(W'i00 ~amplil:tg.Si~(!j long •.rml~ om~rsll!rli(1ld milaktl: Cit')i',lna:1s \'\IIL'lre oolllig~(1d by st:Ju~!x-.f'iiily diiT:mc· f,~ib~¢ d'\li:s~,p<'i!mli.Q11I di'~m1jil!1!.!1.(;~w rooof ~g!l.,al!.d (DIiiC {lifd~1W ~s~1& wa.. eut arid fO~· ~oo ItcOln (!!!.I!tro~rv~U]Q~ (lfiil!g[~dty po~ilkJl'l I~Li()fl$,\~~~ <We :m:imroroed ino'he oompornl c!~1!n~ i<ihcd ~o ~1!""e a slI!rfaoo ~J]l1l!tLo;: rnu:!.mU~y :sWW!~. ,mdi"fil!1-,<d~)!' ·(If (he diro~! :!!ondi.ffwcloo 'e~!;1!;lfo!! I!f!ot For dtcse C!i'J',s;m!s, lh(;l <cl~a)I.lc:!~k:h~ysl!llresis OOI!ln for ~!Il!'lail a U min"le deilays ..AI: 5Q iIlCide!'!oc, (II,f ~esLJUC~ll!re facto'f fil!f var!ol!!'>i!ldiocs. BeUeari.~ Kv;~s obsCI"'!I!ed,. ;i.1i~3W~dthof 5.6 K.. w 1],1eco].ccnr:ons dilTrno[ from all:aalcri8illhic:b~ of ca.IlISCIh.c!UiOI1Srtmumirm mk~,p'l:aoe h~ a s.tar\]u£ly [n fiig, ], B to E. I(he SUllie, ,el!t.1i}IIDI~ di:iTruCilion aoo~nlO 1~11Jl; do IUlot OihscM' 00& in, tI~e difW'C oom'Jared systmn,. !lImd~pe"dcllec' em cc::mit2tiim[ :m iililt::idcnlooaillg~c of ....5 rrnC:~.ioop:lt~lflms Iblll.t iUlS~@.[I.dI \.I{cU«IJ!Il('ldB~g f1J[ml1ooiscvidlclt~ iUa! lIrtJli'CSlIQ~du1~a!vio:r, and W!(l :p>alill:r:I'nS,tmlmIlOOm. b ~liI!Icljoo :wc1~.d'epcflld~)ooa!I. slml"l.mdil(t!ltg UI1UGtll »d at room LttUilT,Jef'all!lre:(a1lM)moc~ildc: jllla.:'W:)1 are spots, .s:tlggesnil~gdN!lt ilt lea ..n ~OiuremLo:tl:tl~ lay~~e·(lo:m~1 ,d!i!mcliOO'!.~ !i)orUrib'll!l~ ~OW!~ ~rd1iffi.lre!lt ~rr.m~ ~Wi'mll<l!~ d:iroc~iorn:, fl., ~!$in. t!~~ I!~ ~ll!ctcl"Ue llle !wue:q~mbri!lu'l'! lim!1-rS[!iOll(oom i~lg to !l1~~!'!ooderef1;Qes(18). A :rou,gh ,esli~1<l1i;lo:f aItld e!~ctrol'! dW(lctiom, (zone: a"!is). :V~.AU ~~'~ ~~.~ic Illo1io:!!IS s1~' .. !i!J~ndwalt;'~ l(ilI!lcl ro ~ts\,;'Ufe ide!!l!ified! <lSll:lonoohlllic va!~dilll.!n tiile mean ~e ~<J!II~ a 30"klN e!'e(llfUn .g~'!fesa of cm~ velocity. dioxide; Imru;l:l'd:ssio!lI~ltkep3Ut1:.nlS oiligtmue from, pooelrntl(!1;1ldep~~ (...5 11111) Iba~is aboo~:.10 tinncs: A'l equilibrinm,. lhcpbase liIi'3lll~:t101il iI~ tll.rgcr Ihfli1l fhe interpl311M s~lThfflfial!l!. fjoo.,Q1ll5fl01' 'i!'MlarnUilliIl diOM:tdc; b:asbce:ca . .suulUed by C;'(runilill" l>!llrFacc glITlCR];l'OO (tl), and tbe sil~II~s:~aii order is l.W1.dmllin Iffil.G: ,."",~il·~.l:Idellijcdd~lfra.Nlon imgd,lG:c~,m.g(1l of ~.ml C8pg.city with I£I.np()1t1i1"c S!lull angJc of iilJlcicfull.Oc. th~probeG 3JlCl!. Om. 3:1~ (19~1). Sy(::mi :;;llJ:di~id~nil:ifymllii~ Imm8ijl~mll pal~l'ns, Iil!ie 8I,lrt"lC'e .is ,..,..2 :1TIttI OJ' rn n~m,. vin,g; ill glloo,P ~ U fir;s~ order W:Lt!~ ,~ hysle~is, Sen'binl<1i1 COinlri~ Wilth SI!.!Ch rich d;ifftmcli,on. ~6 of !lie BI'<I~ velocity misrt~tcl! of -2,0' IJ'5' betw~en !.he (lptiC<l~ i bll!ti{l!~ l:!i8~~g o~ti.cjl reficclio!l!aJ!I!cli :toi~y ~1'K:th,~ spots we~ inl_c!!Sc e!mllll~1~ few ~i~~",rew~vedn· ,c1iicimli(J]1.u'ld lI]~e elecllxllt ~!J!]se.s. [;n order 1[0 vcsligaIlO!!S. 11t(;l dh!lJ~igc ~1Iru> h,!&gj<!lI)OO, I!.!~ing [lvero(JJne such RliS!!W:OIkh OI.llG, roochfs resoil!L~iou, by oct> tlacv,e iIldllC<iwd! Ute !i.lllmlf~ 1!'a1JI.WJ·c of Ul'C: Ii~eopti.c;!ll I;iInllse\!VaS:li~rud w acl:deve ttlmpom.1 ~.ehrollywidl '~Iffi;eloolID:lfl.pae};je~audmentill'll A- . IFig. 2. ULtJra~afitbalild pJl~, ,aifl',~amom dry-' probed! c~l S-MaoL'l h A :fS;IroI[lsitmt" ~Ql(\!I. (2' 1!iI,arniC$ ~f th~~~r,a~ pl!¥;e 1!r,an~til)~. ~Y~f,m.dll!desooril"..okJ!io!l frollttl amy resid!.:l~1 I(A) ImlNl~ity challlg;e: oflJ1e (606) Brag~ spJ!ead .W!:cW dle :~lfIvolvcdJ dU1<!liOlf! of 'o;pllcal ru:!'d ~lPatll'l!i'tilil timJil!. At rle~y' with 11 im!!!' oom~' electron pukes, .<1.5 disOl:ISSod OO~OV\l. SUint T:Ii. (If 30i]'fs 1i'.igJ$ oo:t'ain>e'dl'()!11 thlll to,t}l TbeObs~edwnllJ0rnlC:lmm£e of fn~ensil)'o.f l£ilnE!·scaleof :1:3 I~S· W.O); l!Iote:IiH,e: I:hlilllge OJm elas..; of Bragg ~s, for CKflJlllplc,. ~m ,~6(6)1 in ~lliItelil1;ityol'diffil~acti(lill~:Iil thJE1250·]'ll s:po~, is shol!Nll1.in fig. :21\.. \VlIh l'im~ s.teps SiOOps,. ~In 11~~!iH,jW·~hil~g;~of {~06) i~bl~~) :2)0 ~. il. Immirlro d(l'CreMe in ~nlEnsiryis o'ibalnd ~091.) (r'etd) spDt5. with tme.FDr.aU 1m,. s~J'Yed. ]!]~'!'dleur to NCordl such <J. ~;;UlJ.~reiln.d:]e veEiDlJ!8lted Bragg :5:pe1i]~ twa, crlliHerMt "lI'Ie8 m~mlber of'e!·ec~~!!S iu~'~~!i: Pll1·1&:: ,:101M !:ed~ ~Q !Of d~liI'ii~ ~. i(lb5~f!.1e~ .~ rt:~I'II1~~i!iId ~:500, wlrlcl~is be~nwlile SJ}a_Oe~IHI1!'ge HnTIlil dll!(ay )imGlf M th@ b[U;~ traG! was II!IlIBlI~ UI" .t:1).~dlin d~is, lij~nitof ~OWfli!lUI. I[he ,e~(Xtt!iJn, ~'IJI"edfur' (8®6J. (826), (82"6);, (846);, (8 4f6~, 1 2 3 p-i1lse wId:dl 'lWsm~rOO (32::2:1: l2:S ~'i»ilJ1J sitlIl. 1~6(6)'. (7':1,4), (4·j1), (10 :24.). o'!IliId1l61,8)~ ala $~kiffilg spoodi oj]' ~,4r)± 2: fs per p~el (29'). ~ deGay with ell dme wrnstali1t 't.~ of 9,,2 ps, Gi¥(.'udlC; opttcal puls~width.of]2!O fs, dle; c~ ~~!m~W1lf mlJae Irredlma:~e. W<I:8ml1lBli'IlUOOfoll 1(~911il'. (084), ,~_f!~ (Q18.~11,,~. 'th~tota~ ti!iil~ OO!'re!.ro(l!] WM II.!Sed h~~e .~.n~}'s~f nl~ Q (606) ~~!~e: of 40 ps:. llie:telll'l:pcwal !:jJllfig~ vawes, ~!~e!w, ~ws {11J!a!!l~gi!! drne QQ~.:;;trnl!j tto of I{Ai~1 ,md At~~over WhtCilil the -d!scajl' ~is 307 f:s., 'Ii1w: e.1TQli 'ooli~l:ea.ch. dre:llay tijl:neis .~.feS\llt {09 1) l~rOililOllliiced ·:;u,e 160 fs a:nd 15 p:S. (4(:0. Th~ of I:I~siJi,gle m.ea..~r:e.nr.;llts, :For ;1lU'afthe ,8i1<lgg i!2 ::;;.'9.2ps dififer@IfUlei"cika1~a SilEpWiS!! m&h.al1liSiIilli spots s~udkld{r~g. ). wcobscf\lIOO [1.'110 t~ ] of roraml1l1k I!mOtiOIilS. bchi.'lvtOfF~g,2~~: .ilIc (~ d~y imI.il.~~t\1iIS;~ybh:ue) ( ( ~1I1mi!II!i H) th.i!l:606) ~tmd!. .~rb1My~a. d~y ( Jac'ki!t,s Sl!,l;:h f;:i,.."t' d)1W!<l!!flli~sbut clI_h ib:~~inl; ~m inl:ensity decrease with til. ti~l1leCoflsJ:<Jj111j t2. of 9 ..2 ps (red);. iDle MiIIii;)Jj r...dlces (11k/) ofih.~ l\,!;10 ~10 o 1tO 20 30 d:ll'lilSC!! of :spoL~~re ~:ist(ld ~t1. II!ilCl I]gtI!reeap~ion. iirn.8; (pG) \Vt1 oot~ Iffilat no s1~Hlii~ ~iilil[l orchru~~ in wid:d!J.
05

k 'Wiij~c'hemkl!! roaCliOJils, I.heoo~ of concerted (0.1"oonClllnmt) VmmlSOOlllSCCuti:w l1iuc_lOOlims H. 2) beOOJ:n~ CiGlflimlro iMlldc:rstunding Ihe ,e!rnnmlfillyfi~ps of

d~.c: :rrequitedl; ,ex>eLla'nion a, v,iIIliiilileC~!l'ro.clerisllic depenrlemll 0111 am lworpho'Jogy oflhe spcdil'ic !>.,\rIiIlP~e.R~'tl..sparoim3.g~llg (and di~ImGI.icl!ll) wag; 3elili~'I:'oo w~~hUEM rOtc I'iI1HO!lC3~~SI'I'JjO· I!Wlei'm~c'Ilru1iSlt'i, ~ij~~'..q~@~il)' H~,\'Vle ~~tI ,on II!1~g"<'ih~rgof 1'U'aJ'iJ5iitL\i;iOO~ 'llliflg\5 (14" .1]). W~i!l¥~llS~OO{!I ...ingle c!')~1s gh<J!!~ .dIiill!!rto;>;;ide,li'ivdked !iILti}· a ~w!y01:ii.l~ dUicil!1,gas~~elty~~tsh'ig pmc~ r~ e~eotro!] c~~.lo,gmphy l7¢i!h a L1TI~ ,geOlU· fwm '~!!l~!:a'll1mJl!()!I;~i!lichisl!i~ai!QfHCl fi!l.d oot!'<lg'" : ( o'lnll {1~lal)1 O'OSeJi"i!led. WLd~, 3Im:mic·scaile spaH811 ,(loti)' (U, 27, It:j. ru~dI~dli lhe 3D f\%"~Ilr:ca~ ~ooco:f :IIl'OiirlS iI1",o.~VM (20 BmU ~). and InmporalOO$.Olliltum" Thesll:tdy is perrormoo 'TillIe ililitia.1.aiiid f:ilmal ~rryS1i:li!1 :!>tlUCltllires of va.· !JIll. !!ii1i1lIc:eiJ'sta1s. of '\I.anooillllfn (~tolllkle, WhOE ftg. ])1.:: iw I]I~ l[lhas~nl~i"O'!l ~i~ibtDs '<\ i!N¢l[l..d~fim~d ~ly~W~1:s !~a~lI!Ju'!ldiQ)(~i,!~atl';. d~;!el~i!~ ~I;~ern 11\'lQ th~,!OO)"'!ill"liC01;lIy ~I,lli snroeu.~ !lXli:~a-cH!l!ie phageihc v:ru~~I!.!")~I(1in'L"'~''iWl in.to. pU:s, liH!!~:in ~elewg.onotl :p!~le {~rerred 00 !J!(lrd~to map ~1!!9aw1!!ysof!110'Iicm, allobscrvecl as r,!lItl!e)a~1 V":'V dist!l!lces .are L-qu.1li1 lind ~;he BroSS: difradLCO!lsof dil'ere!trl" plal1le!> <liiDdi 7,Q1Kl

Qr n!ll!~~rlK~~iQl,lS.

sg.p;1~'iQQ

of 'tff~r:gl!!t it:\1i!15i~g~ (22..,26), 11!eln!!~tiQ!~

:nmlihernll<li~~n aIle ultmSl1!Qliii o

C<l~ bei:~dll!ood

t~~1eSC<l!~~ wid.}

!1~'f~~nr~ (800 !!I!m) lP~t~j<!"Ql, ,<l!!1~~ v~~ ble d~!,OI!y tinle, 5.truQ.~J:l1!1 d~m~mtcswe!'em~,l.oweCl by di.:Ilfrnct~n!!l d'\eeieclro1il lP~d{cls. 1ll.e

or

REPORTS
spots'MR OZ) S~(lWS UgallnQ !!uIbsi.rntialla~lioo ex:pa1ilsiOJ;l is InElldfilg place on Ihhe lIlmlsh.m1 '~nte sc,,9!l!e;llliI.c 3~n.oe of 3 dear 'width dlQllg.e also iIllQIi:ealm; IIwt ne IweaJl'!!.lr.WlblJ.e disolXkris ~iltrodiilQOOOI1 tli&-: tilNO: ~1.c" n,~o~iVat~(ii1L"
W~~!1~~~~I~

~u ~b'

t~~,~~~. ,<l,rg~ce TI~

·Qf ~

~;;,;;-

ch.tde th~rm~~i!;pa.l~5iin!fi Ill' lattLC~ inlio:mo~~il~y

(~fi)i!~ Ud!!, t1ml~e I~'ig:e (28,). All B~gg!ipo!s ~h<!J! show j[le 'fs beha'lriot i1ilVo!venllUlzeY.O 'l'ai~ues ef (il1.tJ), whereas tI~fise

•••
a

and ps :il!lUi)I",,-lY. ,e~13ng!Ml gf .8!l<igg ~~lS ,at~ ~"5QCia'!~dwith !1~tiQ"-{lf aoom~ \lI,';itl~~~d~e u~l cell by dleslructive a~l~e.rrere!'l'Ces• .tod these • c;lJ.an:g,e8 ,Me delCl'1llined byU~,e st!'iUC:U.III,'e fuetOf' ~nOl~illl1i\'!C1 droil~~ctl'>ily of SC1lilmerod ClCcmJiL'l tn fur a :glvcil dlre~iQn aIld :i!lQll~ axis, ~llOOiflcaH)!', 1~IhGlimU(lMil)l 1 {)If.l:'lJ :l3mgg :~I (kk!). wMeh. L s ~lQpilll'iol](l:llto Il,~ ~~a~ ofl!'1(l ~fUCh]i\I;'l rnct~t F(/Jk/J. ~ clctwninoo by ~lIiIeposilion Ot)!l;) elf 'iIlO~ll wilhh~ !!he l~mDI0011 (Eq. I}I

dispilaY£fl3 Ihe .sIQW~ jJ.'l Mh.!i!viOr :lm\'S a zelro comjl'OfKlill of h, A.oonudill!l:lily, Ithfl olb:oeJi'\!loo fs

0"5
,

.F(hkl} ...

Lhexp[~21.i:,r:
i

~hk{)·{~).rJ
,OtJ;l5 ''!PI IDJS!pllai~ei"iit

't .
'O\.O!;i: 'IF'" Displlao9li'bei'1ll(A}

wh~~

J; .is· tile ai:O!lltC ~:MILWil!lg r:acll)v.1]l~ ]11~lOOli!'l~cIPlge :Im'i il! ~{lwcr s}"nl!~lry tlw

(.A)

(]If thernlilie phase, aad lfihc SY1l11'lOOtry.r.aiWsI~,g 1;iI!1OOessG£ csuse ,01 .~argcelmn:ge ill. Bmu dH]'rao.
l~tOn.even when ::>1!'t1iiI11.aJiiillpniutde aoom:Lcmotiolls a~ invOihiloo,a.~ S~OWiru Imelbw" 111';O~",OO two typt;$ ofdy.n.<'III'I:iLcg ii:'K!ic.'lOO' srepw~~ alo:m!c ialotrO!L'5lrMb!1g diffe!n;:I~l di~ l~im\£.figl~_re 3A depic~nte inilial and :!ina[ li'flII1adimnpollilio.uas: iu d!m II.wop1ilsscs" froJiH the iWillcr Il~CI in Eq[" ll, iliS C'\I'iCilcll~hat 81~atomk t :nlOV1rnllGl'It along III ccnair.l difOOtton cam. (un[y 3f~ f~m. ~c1il ..iB:ma:ggspol;~ dnm hacloffi IIil000Z.ero QQ(u. ri.

lmm

IS
1.01

•
'-12(1
(I

ii'

'"

Ii

II

II

M:lII,C$ :irldi~.lt ]8 l~iJl~ooncl'udecW th<l!llhe ~~lhi~i !]lG~:O!l is ..i~,g fs I~~ea !il,;(is, wllil(ih~s~le dirool!rnl ohhe V-Vbo:nd
bll!ii:o!1.<; dlC:oo~~'ldiml.g hi! i1ildlC: "nu:moolililac S•. c!lml:. IDirl. Id~.cOdlC1i' hand, 1~~lCPSSItl'iUctuml mms:fo:m11i1iIio:~ p:00Jl oots .a:lm~'lll tire c and b axes (ffg. 3A)" ]f tile fs iIi'I1Ot.ionhad: '~ compoonml.l~ aklllg b or C·, II \V(lll!d:sh[}w !J~' in lire dy!,..unics~f<Jin m"{~lipdl :5!JO'l Q(llJilimry to s,
o:bserv.rl~on'iJ. 1b qli!<!!lltfy selec.dv'e

:2040

'so

OO,~ 00

~2014<l

Time ~ps~
,_
~ • 1i'!"11 I

~ ~~

~·'·.·t~. "'_ .

f~~l:eI1:i>ily cl~lm~cs",r~ caloollililed :nw ~h.e obscNooBra.gg (!)fr:flreLCtiom the sUi'iUcmmil''aClO:l' and. dltllJ3rusily d:wt.rlgcs o'.r the ImomocldilitC !p:hase wilLl'tldle: atoms und'e£g(l' s:ma~.~. ~g",~k: diSf~a~~:l1~~lS,T\VQPQ~~lbl~ ~tlYwa~ fQf ~w!l~lc nk!veI~"!e!Q~ \'!,1\~~ oo~s;i&ret:!I.h] ff.g. fj.g. ~" ,tI), ~k !1f]g~m~mts·andl ~k~~dl :stfii!O!l!f~racto!5, ,ttQP me II~ij~~(PlifPtru'!!!I!dlfhat(b!t~) JA, we. d!l!p~ay t~~e~Ql~e~e!lcc(lifV-V 1)cmd~ pOsiOOliiS offthe Viiiililiditm ifIDllIi:s.. TliJe moooo.fuii!: ~iiI: :eeIItill di!pOOtm .as,~dj purple 1~n.e5;alfl~1 Mm~lumt the wcak~n:~ng:(or diilati.o'l1.) motl.o!n, <nil, vill!.ies (If 1(:eIlI.aJ; 11lijLll lootted! lfuox. Uqp' ri9f11r}1 The direct lOO~iDn,~ff the'lltllllllriium .1Ilromfrom tIileiinmai (p~M to the Ifl3~ilI!~1 Spools wi.lffil II # nsh.O'W' :JI clllcrea.'>(:iI~, fi~~ (tQ!ue~ ~sl:'lioln, Imm.y O!i~gl the II; .arl~ lis. dep\ctOO.~13G~ klffi S'b',udm,e:foaM' a!ildl~~ trn!e1ll5i~ i~lellSil.ty.ffWi~ for IUn(l.5e will~ h = {}Ihc'int'Msjlly ,~b:mge: f'Ofth@ tilted Brag,g .s,potSror a! cflS~{@fI1!mt ,00the varladium .alDl1Ifia~oo!l'·1Jl!: dl!1itii~.G3l 0000;, as IrnltI!Ltttn.\'l ii!litcht:lI:tg~., a\l. ob.\'lil;lf\'ecle;.;lITI~riilleiltan1y; ,dep~ed iln '!he IiDp left inil3~. Ol:O,1Ltoimln:~t) S1nmtrull'efam and iriltel1t'l~ 1c!liIal!l!,le fa' iii d~ta(errJ.enlt o,f the In CQmitta'JI, .~~. cQ~dcr:ing d~cl :mOi\l\e:n'e~t vartad~1ilil aiOOmrS, aWnghdir;m ,nh, es oopltmdinl U~ 'mp r.gilitt ]mQj~, 11IiI~ 1IJ~"Ii diisP!a{~me_fIIt:s5hQllilfil a~ ieacH~g 00 ,nlie 'li<lasi6g:n fr-OlI~ ilw: 1i1m1QCJi~lic i!O for rde~Ylm.ed 'e1!UllililIDn of '~1iIe lilIIla!. ~B) TlIfarultoclIIJtll ~ [eo· dl.uilllg me' lIi[~ I~ trnlllsrorm'atioo. l~iIlerut~lehase, l'I1osl spool;S show an increase ,ai!1t~ IToplllfhe iIl\l{penimeml£ll data" hff:re~IOO p (6B6) ~.'(brnEl'), lrillillem ~oo s.repwi5ea1IlfiI'iIE l1ilJilicm MIti~m thill' IlImil:lle~1 SC1llle <I, decrease in IFI~ V"liiles, a Ix:I1<llviorlhai .a:!i!d;.: gji! t!l~ ~~grlh ~let of ShOOfnliotiQli1\ Omd' Th~ditffer!lf1!OO·iliI ~tk ;l("*aypa~s: ~~.I~ooQ(!mic was 1~0'~oo.'>CN'eodi C'.ll:)pcriinmiit!allyo:l'l dt~ ullrafast (lm ielfnp8l'awr,e)!lilllld IMl~e (higiii m.wWre) ~al'laimW'i diw:ifJ\e :suggeSIS m-a(resooph: s1iiiillr {~!iilliid

I~ro

me

I~:ime seals,

,~Ii!u;enillmlL

~Botrtom)1 .ShcwlII iI!Ir~ Irilll'liE!!'iat 1h~ rnrr~"mclin9

ijifil1.iR!> u~

t;r:.

t~ almdl :t~ of sm..mul!a~ dilillilg!es•.

REPORTS
'1!fh~ loiti~~Qg ;};;cii<!'iQ!i!. ,U

i~Vg!,,'CS,Q.le d Ixmd,w'hkh oamesfwm ~d!~n,g ofdle vaMdi,umprurs (J:O, 1/), Fil'Ollil::iiI chel11li>C<ll1 1:i'~1li,ve" tbc cxcilnliOOl is to al] alitrOO:tad~tlg ~lom, wllicl~ iml5lmJUldyrestlllDllif~ 9, r'L'.iPlili~'>i\leforoe alit ,jEil~a.I:or.l13.a:ndj Iil.~~)' ltral~ alOi1~ !tI'i~ bo:ntru ~ di~LOII!.II~ ~ql!ieilOO ~iid gil a 81(;~~1'timc; 51~Ie,
I!Wie1i!!f:!JulceU 11,~tsfo"~s l'O~)iiaOO lhe 'oo!WfisW'lMtm~ o,fthe mlilepha ... llteref~, dl!:l dbserved! step..e. wise aw:nlic nlCii~iO:las, s1ro.\1I' I11llm:lmm l:i'hll£e IJ::mhl'" I sjm~Qn pi'OCCl:lds~y II, nlOOdjil'ool flilill~w,~y om, the :~nill!rlidiunm'lsi,Qn::i~po'lentia.1 l.mcrgy !i.liif'aO~ ,:li.Itld

'~ss fiV 'pri~~ly

o:f ~clyral d~~nk,,~, A.~ ~hQiJ.\\''m!i'~Fig, :~" 3 <1i~' i!1;~ in~!Jj<!1!H...~ia(Q!"'mctal ~itl.Q!1 .Il!n-er a
delay,. dl(.n is
3. (lomltim.!led:teD1l~or:'1I1

chatlcgtl of

~ot by

:(l d.i~l ~11.i'C~1!It,3J1 o!w~n~iol1. r Sevcffll po-!!Il'J .t!'le \7ilOrlh ~'I1!iI;,'!!l~oni!l!J~,l'i!'li~

in.ten!>ii~y l[Jml!()\IIe~..off all ..,.30()' ~IS.Gi'l!lml !lm opnicat prn1e:~lllIt;iof~ depd~ (il~;} -~ 00 nm Po) of aII\1llil!~ 1I1~'ial dl~W!,l'<ioo OrOOfflCL'Gill,of 0_0<2 i)Er/,g (20), \lI'~ eG!1.(;1I,lI{l~ d~ ih~ oorilduetio,naw:a't from 'ihepWood ~a}'lir!'!l!!iJ_slbe :$1Qli.'\'1eth",-,,, :1 ns ( ,ilIIlO C11!1iUlQl e;x;,plai!1! Ute om.e!"l.'cd ~iOO-p'" ,ay· namics •.HO"NOvcr, beeaase I~hc ~pecd of :!i01md in d~~iDtill"Ulil is 11~ 400D mt~ {33}" sll.e3Ii", WI~Lchis H~y for Ilillle fnooanon o:fnlrl!('l WIl!lldilJllfiiJ

1!lIi!eseresolvoo Sbuch!JICS!lro for It;'U~te!l~ spcdes, en ImUle ~,Q, j],1e :S'IOlble!1!!!lilielrLlCottue,andi 'il1l'\!O~ve IkiJ~ i!>rll!rther!>ll~;!X'l.'I!edllby Oilher OOS'le''''l.lliIOl~S, s F~:I'SI, ald101J,gh tlilC Bragg S:poll'! !.'l::d~ib~.tI~rnm a laudsea.pcwilh distiilll.d coomimalt!S,,~1l1 Fig, lB, IIIDIc ovcr.:1l~1 IlOlt'lporal bCtl~8J\!'iQx' t1P~Q ] .,:2 filSatl'd, game early f~-ps behavior, d~ey ~ow i.nttmsi.ly ~ml(]ll.lr$ll sma,,""'I1ot~are sl10\\l1ll1. Sec()!f1cl, tn.p~irn] inerease ~room·e&~eat 1lli1.~ SILIb·ns s;c::'ll~ fa, di rfi~:m~iOIJie<i!Xl():S,oolU,l<is'~~nm 'W1(II rs~~IOO:r wc:~~~viA~ <llld di.fftoot~n fro!'!l ¢iYCf~Sl\'!nirn;: i~~,rl~nc~ (37), Soo{lfldjw~e!ll 'lJI.leob~mcd 8<'!nl'pI,es pfOyide .~.~ ..erOl¥.e o\ler1!]1 ,oricrtWio!L<: x.-my d:llTrnC!lron of 19~.e crystal III! dlfrelrewl~: .wd win~ive :rige itO c(lrl~:sil:e In:msil:l!ltbCi!avior. (Fig. 3.B,insel) as :i~. [PIBSSOO Cawd~£ri el' al: (2.nlmve ffilowl~ Ilillfit. x'riIiY d1if~ ~Dliupem:lfI'liCS fmClioo amand Idm ((H 1) ~1 regicm (12) oJ a IhoolLlgh ~lljlCP~IlIS!;l'lr:3JllISimtof:l!"Itllilrl.y an BI:il~ crysmlis aOoTIIl91M by ";l2:w~5 cl1illli,ge, wi.lllI. a .ots \Ve~ oih.se:rvedito. move angtnlsdy, in.dj.· lro~!iu.v€ly small faJ>l.e:reQmpo.niJilill~. tS300 fs). 'Oiv- c:rUI'Iig m~iilti.cm lor tim pdnei~i~ axes. FUlidw.' Cll Ill\r ~"1!11s, W~ co:nchl!~dlllffiI<l!1dO~liI1rOU~ C1r ~vith~l1c~ c(Dmes!WQI'!l the nli!~moe depen~lc~ OlItld ~n;:d'llreslwld be:lwvw1t. 1!IIi!Cfs dY~<lIf!1~cS, l!!n e!ll!~fl:l,e C Ihere!iJ'ii'rn'lil Figure <I. sbC)w~: Iiliu~ :lllue!(,lCC: depellcienoe ·of ~oo!iCl;!il diffrnO!'ion is m;oni~orecl: and d'iolt '~II,eps ef coonponmlt is due IDO d~CU1lflS\rCriS8J~IliKntio:~. hst~ <ililTlI'3Clio:nl chl"lige.~rnr ,exrnnp~e. :[ordl~ (606) ~y;fer the firsl Sllql', OOlnpariSOll wil~~ ~!.h£... lOO~fil 13l!mgg spal, atlWQ ~iflrm: poifl1iS, .t. ... 10 [Dfii :anm t ... ~ mi, l'b(lifum~ ch8l'lJ5:,~!lsp!ays (iillmal;~)iil.lin. d 1~;~n.1~ IOmlStluat from optIcal. n::lillcl.iviiny (13., 25) ;liud .... ' ('I;: ft(Jm, d\~ ~K-ruy ~'lh!ldy (22) !.$ rlOI 500 ,~r dr;;p~dclil.o~winh. a I:ltl~O]d 1Ii1. 6;t1 .nrnJ!cl.rI":. TI~elltueshold\. whidlillt1l!n~lal:cs 001, "'"'fU:lr5pbonon S~!@i'htrofWalid\. boc~~e !'he lb!'lt~cr~pmlaChus perlo'ID!.. dJll!.!!Tt .Itom (38),. r.ndicatcslhc !]l'~qin]Ji!Jn ~l~ scns~~i\'c to iJre 'elocLfOnic dl<tll:gcsof jJ'!ie Olll£!'lCereqni~d i!'m'swlwIJillng into(hene\\\.'pI~ ]1!HJlCfiLd wherel!i!'l ~lhe laUer OJ!IC i!I.w:cg:mtesIJl'C stt'llID1!ilml d1fl:1il.geS olVer d~e x",.mYpnlbJng 11.m®[J~, in ~bis crysla.llinc nmfftGr~9l and as s,uc~.dc::I'i.I~es ,t'llevd of ©OOIi!l('lctl.vity 8niU)I.ngd~~ ffereli!lfS!te.'l clJi (iI,f :m:tiCro:l'll~LQfS..Full:l:l"C' ,experim.cfbru;~naYI;IJ\"'e3!l l~iI'I('l vibrattonal Ilin'9!': seale: ,of -110 rn of {Ire ifmvolvcdl. (lSDb far l!Iu~SjlOlS lhat ('lXh.lbil the [0:; "q,lIJi~l.bri!X!ll S,nll!!(;Ul~ (llf;~ ~1"!~wru.a,1iong.ef '~I'I!t¢ d:ylil~micsi' w~ ~ot~. dw:t Ou} thr~o&o,1dfor I~rnl~ is due '~\J ;011.pote!!A:ia1.<JriYe!] nlouon, fn lili!le e;li;dwd SIllb-!1B (;l()n~p,ooe!~~ e:l~1I.,'T the sa:!t!c Of Mgl~er d~Il!~ thoU: (I f ~W!efscO!:!llJO!]e1Ml. MJgge;fill.h~g~,a:] sUltc(.?K). dlC shear Is llS!lOclla~cd w~Ahl])le :tnilh:ll almfnic The I~mn~rh:nlbc1JuJI'Y'iOlT on dile I,oager. mOI:iOllil), InfW,lOsoo:mdllme scalc roVlOOJlsaflod1~r dinlimsuon,

dit:Ll!tid~(34) and Wllay i'YV"ol",,~ dis!oca1lio:m; (33), w~U OOCIl!!r :~. ~IOO 'psfu !, 11 le:n~I,1il~~ ·of IUJ!i'!~reds of n<li~OJlliett~s (36J TI~iss]le:;;wmo·
l

(0.38 Jhmn3) fot lhen~n,h~dud"g ~~epii~e: bimns:i!iof1~inC!llU(!Hng title lalea;"Il ~l (l,ifl}.1llis h o~ scNa:niOlil SIlWSI:slhat '[lbcpJI~~ tt'iulSimion is eriliic.ally ,dcpGutlG~tem. the 'Io~l l1u:lwoor CD!IT rnrnr;;nl. 'dl~_~ a.ldo,p:Ii~1 (206). Ol!I~dt[~a:n Ul¢ d~m trm~L'O!W~true~yres !'!lJil1e'~cboo b si!l1ii,my but wiU~ ·diffferent l<l_tes, as 5110wo, for e1>!!lHlIJle,in S'!Jfr:aoetf~TII_c:u::I1i::'w~I)" (39). l.aSl~,y. we havc rnpcmed. 'lIa~seCXper.,ll1l~l1lSm di:ffefi!.:.~lt ruiW!pllitS.rwco;; at] 10 K,. tim nucf1lCX': 'I!hros:tml!d,
!ll~lns 00 a higillGii v:8Jll11Cl ,ool:rrt;p!3!ii6di wi.d~ t~~~t31 K. l>vh:i~~ furlil~iI;'lf~lI!Pports tllc:a:tH;JoVe>-

III ArM ~:tu:zM v-v 'pajrs" W~I~~~~ Ih~ Itllil~~. t('J~l e1tCfgy d~posi.ood at tirres!hoTd {-0,4 ± 0.. r 'I , ,i.-..4 8 ItIiJ'ib, .,;";",,,'' '11 -~.w, n\",r.tni~ Iffii e ~_.~nll· -1-wq,'!:.!_,<;lI..!! .. _ ~ "'''''''''-''_c'!l;.e_ _._. - .V!.!.i!.!._ea_

Ffg~'l1gq.1 , i.!~e~~l;~l:.1t~ di$D~e~t (F~. 3 Ajl ~~les 'O.,(](l A rQr ~ O.·~ p1l!@rlpoer VJ.!lllmUUan fO:li dCIQemJliz.!."I1. ,e,.. ita~iQn .oF'[Jne laitioe. .c ;Howe~,VillmciliL!iJ.m dioxi& is 11 $mngly eorreluted. systcn\ rulod .•hig valll:c could '!be. 85 high as

v-v

me.l~Q~~ :slcpl!i.vi\le

:nno

l'l'!eCI'la.!]il:!"It

The 1!!bi~:i!:y 00' decipher !.he !il<llu.ire ,of t1'11ll alomric ~lJotiOf~S; min,ga S'tIJllilClJlilt'JiI phase Innn", d sii.lioll. lSi dCmOfnSU'al:cd. ~!Y Ida,c' mm~.1S reponed IrorG.For vamt.dium c:liox:i&'crys:lal~!. d1t': cl~
1l%'t'iI..'UiY$tl1Ps

ir

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rli8!ll1 c~; ilm 11~q;l!.!e!lre .of tmlf!.'iiit"ill!!a~ Sfi!"Ul;;I~, ... I1mI ~fiv(llvi!,g ~ dis:p,lacemC!lt'i Of:!J W,e fs and! po.. ~ume ",C<!leoo~kn~ed! by Im~go!r.l!l.Sle ~leolr rea:m1f:tg,CJT:I:oolson tIlI.c sllb.liIS fim:c scale: iilnId at ilrl£ S~~IOO of sound, 11.1:(;V-V bond d:LIati(H~,~.5 the Jnirial S:IDJ:D' of the i:mf;:lJ~,8iW:l'.~o ·lIiJl.~ta~

fn~low

3. flolnornlmrl.ed

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IPfOvi,~tng 11.dynrHllifll!Cf,jJl m(],l~Cl!lIlr pi(;t~ 1I1l:iCc:Ola'l!;:udel'!ooof the 1fI;1~1<l!1.lnd plloooi ndmoe<J UfwliSLtkm iI:tuesk(llds lIt diITe!lei!nl W!1]penllU!reS S!i.lg'!:€iStS ilreOOllll:n1:lOOl p@O~WiJy IlilJcchaUlSl:r:l1for tlm:IroMilio:n. W~tI~ atomic;., 4D srnle: spatllli.fL1ild. lmnporat rnsolution.s,wc
bia.iL~rgl'lltilO!I'~iOrl;

expe0D., by l!i!s1lligd.1{_~It2b.lc:~t()paplpro'lC~, rn<any

fU~IIi.Ir,e@(:!eltj:t\il!IS

ill'! th~ m~dll,e.,,;. d~igl!h~d 'of

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the h:liiti~liii'!t~!'IlSity

decrease ,(YiI1olet) .am:iJ the <llrn'Ii~~'lDl!ldlll oiF~liIe l~ol1g • tim~ d1~!il@ (gr'~!1~i1!~ IpIDttedfew differ1mt 'eK(j. t:i.tiDIII ~uelllC:~Ji,. (om' A.
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REPORTS
1<1- .M•.. S, GflfiO(jj~, 'Ii. )\. tOM~ImI.~, W!~SilftiflOOti', .. A. H. ~w'li~ I'mr, Jilafl. AmGt Sd, rJ~:5Jl liQi3, 13'l.2: 7 (,'l:OO&j, ISo. V, ,A,. ILw,mov" ] .. Wiil~5ei1!ried:er, II, T<!flI9,/1" HI, ZEW~il, lioI'!rr:!Q' Lett. 1. ;::~~, (lQ 01),
~. 5.1P"'~~ J. S, ~$U!l, 'iJ_·lflL j(li.iO!TI,A HI. 2ew.aiL Na~ Ui!:. 1', l5,"'~, (2:001:/)1, ii'. it JI. (a!1lil!r.~~fI, ~. Il ,r::O!ii~r...fIoc il,[1.lr:L A~ti; Sd.u~.i ~.

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fllN. tell. '91, 025700. !2oQIB~. 19" r. JI. M,mn, PIzy:;. /.low. leii'; 3, ..:14 n!9S9l.
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(Mi6?),

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flllill ~}i! oofltllll!&y o~ 02'l1.!iit.l, th@!!iJIJlIr~tbil ~h ,DlJ!.OO' 1m i'It 800 fUI!'I, (20). [Ill! IJire!OOi.d mlJ[fl(ll:{{lfr,e:;pornit to, <lSO ,fli1]/Inml at tll!e ~!.;(rrilce. 'Wi.:11 !lI1II ,:e[ 'I'~1m!e ~l!l' '!Jr 118 A ~ 12.1~ W1!kll WIllil~!'I5rVW' W1!"!<!lI!1»1l! ~~()!!l5, tbi~ 1,:!i$9Y ~Jty ~'I'!:~-(lQ5 w~~W!'!. 39'. G- £r~~Aij~: ,~~l i1I~~!l f.wOrn,

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:1;6 IEi«.!!!~e:1&trlill'i!: (Gar,n!!~h IIjl~[jj ar~ mnt.lilil.!lllil Ill" strolfl!J •. ~jjffi!ailiHIIl~·wlth ~i~ laUiOO, may ~~M.FII:!IJj~i!mtMn IIII1!! l!)OCi~i.! Itl!!!tllmr(~~!jll blil ~ ~~.im.il!I!d~d~. t~ ill!;u~lrllll!i ~uf{1}OOdiru Q .. E1e!lr~~ 1fi1'!!lIl;iim lrem the prol:oedl l<i~

T~' (I'J,-ef,,:Il1it~~IJ!!e Il',!!~:e~t Wi:ii ~Il!!i"':ed :].00 0 til!i!l:!,~o , ,~~~ ~g~ ""'~~f [:[I ~i~'1M'•. ,rl!!f~ wllkh t'!<!S ~~~ . to be !t!OO 0... we' ~!l! tiil:rt ~~riI¥$im,il!.e;~t)' ~ i~ ,ii1S1i~!!I !If .~'5fl1fl!, itDr III~ lJi'.! oom'JOOiI!!lI. tile! lange' ~ ·mf g Il1:! ~.~ i!iIiiIt!jji:nrom U~~IiJi.ii'i!·
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~fII.~ dil';II'igil!! til 1!H'i!I{lJMI.~~

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'd~Kl:I5ii~I1~., , Iii. Tjeng: l~r g:en~r~LI!llifprO'\!id!~l!!ilme L ,tf'll'St<i~, G .. III ~,fmn 'for lilt uyn:~I,-(vUill1g ,~qllip!n!llll. ,iI!~dIL ,M. Hel!1li~ ~w hie-I,pMtfl,i.!ll: x-r<l!( '!:,!e.l~II!"~!1~nl~, T!tt~~'ffilfk: wa5 ~\~portedl !zy i!'!e NSf" .I,)y ~!~ ~ir ~t;jr~~ Office Iil~ S(ie~i~i(; R>el!!i<utll,~Iid ~ ~l~ OOjl~"'~ ~~d ![!~!!:y,F!1~~r~ ~~m~'frllr ~~«!i !lIi~:i~ ~ {~I~~.
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~llta~ IIiIIItlorn m!lJ)l''~JIlI:l1I!)~or ~uP,Pll!~!, t~ B:r~9!JI ill1i~rri1tit~~O wl.lae.~ ,a~ or i:Iill~ ~heiflili<ll illitertiily.

:~j)Mmblr ,:!:OO1

IM,ol'ecular and Ganom:iic: Data lldent:ilfy the Cllo'sest Llivilnlg IRle,II,alivle'uf Prilmat!e~s
A flllln I.lmd:eor~t<mdi.ng of pnlrirm.te lirl()rp.'l'lol(li[iki!l~ <lnd ,germornIkevolllltio:riI ~eGlnIireS~lrle idellltificm,cDn! of the'lr diOSe:st tiMiill'g r"eloaitive.~m Q:rrder to Irre~olve~~,e am.cesrrai .~eLa,tio:lIl~hip~ amomg llfil'rimate~, a,mdl~,e'U~ (los5tmel:.athl',~,!i'IIe :re.m:hed rnlut~is:~ede5 genomeal.'iglll.llilfliliil1: fc:rr 1~·h.yl();g,oo~'cal~l~ t~f(J;~maM ran~ g~!1omh: (h~f!g,es, 'Within 'the- .sup~rn:~dif!lgi'Q'ro'~P IEual~(h(l!i1.ta, Wi~'kh,~i!1;r::wdf'S;tliN! orders IPI~:hT1litIl:S.r DennopteirCli kO~]jlgc:'S);.IIiIllild:5!:,,!'!'dent!a '~~~es1:l~~W$t W'll:ii'~s!(I IC(f:Ii!$lrl.!cted IPhyrogi!!lfletJtctrees fn:m'l 1.4 ltilobaseso ,of 1l'!!!,6tei'll[ genes fOir n::presentaltWesh"tlJ1il mQ.s,t IlfIIIrajor pdmiUe Illlfl'e'O'i'Qe:s, ltIoth Ie-dam l!:oi~taQltl$rillllfld' 1frI11.!~bi~leiIJreeshr.e!l'lls .• iln:d!:l(fing the peliltail ~ee:shrlfW:, ftI1or;e«J15 ,l'(}~,ii,. ~liIe olllLy livililg 11fIII1l,nllbero'~IiIiI'elfaIlilUy IPlilocerddi!le'. A rel~[I)i)ed llIl1l aID~culard~( ki!lm ..I~~sil'dl!ldlilr:lg I'JJ$Orif!«AJJ su:g'ge~bthat 1reeshllillW.!l <i11'O!'le lp,proocimatei)f < ,53 miillUolII ye'aIUS,i1I'!;Jo. Our diil1iai~h(l'W t'hat CIlJ~ugn~ are ~e c:lo.5!f'it livililg Irrf!lathre~ ,of' prrftlllilatJf:lili1llill'il

S'IlInmnheria (3, 6, 14),. llllil1ml,gh S'!Jpport for lhis

hYp!.]OlCSis WflS ~.o'i'o'CrO\rul for oIleli Iil1Iallltllf'lliB(ii. iaarol"Cf:dill.8l c!latl'(s (15), ,Prinl2l.t.omorp:tm, Propcils~, on IlMltp:boliogical SImIIW (12). hlti ,llIlro been ina,. di~ ~ry SQlt'M!; IIiOl~ili1.a' sJ.iijdl~ V6.. .I 1). Omh!1f
Rliidi~ 1~1i';rtilled 1.O~~t ~~ni\''¢ 1'iI}'~ii~. a!~d(j;n(i!I)'~ ofdin~~U d~c~&Sl.!~ 5l'lp~rt oonlmdic~uY' tQlXilogies (.l8-:2{}J, T>o imipoovc o~r U,ltd)CiI'SffindJi~g of cl'l~'~y eUiarehomm ,evo.~lUlikiil, delYilinc dilJe C~OSCSl and :Hving loo18U.\I,(;o:f :pflimates,we used 'I:wo, f~~ ~l!d~nt iII~Olc(:UtlW a,~~~ .:~ lim SoC~~ii"lOO a !l()i!lrodll!li!&mil set gf ]97.5:22 pm~ira~odi!'!,~ 1)"'aJI!5 &O~l

iw.dl!Ui!te fuait: 1helr ,dtvl:'~!ii:IF!,e()c~u!'fed i!'llth!i!: Qr!rtaali(l~.

i;1~dI'rows

nilEl :iannI, Crl.lZ KnowlUlGenes track ,~:oiden~i ['y rare ~nornic OOa'lflgcs ,fc..",oniciildels) tSm.~. \M.(ml'd. potr:mwl~~ ;sup;po:mIIIncll:ur{!c'fIi prkrril~,y~tlllesc;S. ' We .rlso ~,nml,~ :and arllal~1 .:fI. ] 4-kb nueh:~arg~~ d:rni31t (I~:9gclI-C fhlgqn{)uD$il1l ()ird~r ~ ] to, ¢stima~e .~.pt~y~~~lY~.ld.Ihne~:1e for extlnt eua!lOllo:t'!ll'!Qil~.T'o nr~l~p_tc' a~oti!JIS~ l!he ~ S1i.Me effcCli.'> of h:mg;brnll.d~ 8!1.I.m'ac~,0lil (LBA), wlu'Cb '00") ~noom:lO"lIy placc ;rapidly CVO:I.v1ing c~ooks
11)~~rtmI!m Ilif '1JII!:1.!riR31)!' InoogrOlH I!:iooil!ma!;. Ji~~ J!l&M 111iiM>r~il'l'.[olli!Qjii 5tii~i:oo., TX.771343:, 1J5.i'i. ~(lI!llh!J ~Or GJ'1iII" lflilil<ll~'O'il'GefiQmit$ iBioiiTiIwilllaitil1.5. P~lirn~111~"1ifila, !it1itil !J!I!iIoe!15~~1f.11.!I!li!v~r~~P<irt PA 100®2, u~A~jSlt!eir~!iI~ ~O~!I!~1!'w~, I~ef\!e'. OR '}7i4Il1s, U)A., ~~~!1tM!'!t ~ !\rrq!~l "h:I'sadlo-gy. tJi'Ii~!f\!i~ ~~ ~~~I1i,rMSAi40~yreu!!I'l. G,~IIn<IJ1I1.. ~oo'IogicaL ~nsti}jl!i'!Je'; ]maM.m WOlfg2lflf!1 'G!ie~ileI..Im~~il.r. 1!J...600S4 ~r.!l1:klt~lirn, G~mli3~. ~Natiiflflilll rJ.!4J5@!1I1iIl o:r Natural Hi:!il0f'\!',Smi:1h1>!luian Inlllit!JtiClQ, 'Wash~liigloo~ DC. 2O(!:1lI, I!J~A. :til~J:<I!il1iIl1!l1iJ't of iBiDII>!l)'. UriIi'wrsity ~I Co~fJ)rni .., Ri'!'l!r;liDI1, CA, 92521 USA.

Ihe ~ha!~!~U!i!lversiw ·(If Cailif:or..

:he Qrirgi~s Oi~'1:w.od~m,prlma:~1.':S .ood ru.e:i,[ [fi~hl_wl~~ives. [~lrt~,~_,~opie .Qfi~~eUl.$~ da~Ul P J), a'l filmruhas OOe:n. 3111 nil
wt~M!l pnrl101W8 .m&! iiltle dY'~mjcs evolllU'liQlJl m~{,~U~~ pl:inl."l~e lilfleiilgoe w

Ule. mWH)p~yiy iO,rn' 'l~;Slb:rews, col.ugo.5 (flying I~WlrlJl[S:)I, D!llCi rnni:flflal(lS~lild~e-c.la:de E.lJarch.omtfll, oolMiooship ~CI!,Glirus [,vh{:cb a!~d]@,gQmQ~!S ,(So 6-8)]~lfI c,mjira~!, tiN !:'eJ!@I!Qns'hlps: wl.ih~nE~!KI;~i~ ~'l1.ot we'n reoolved\,(J.losi Ii ~Jl.ybeca.use of 6Ie
mpkl
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(4, 5).. R.csO:~vi.ng, ~i.gher pcima~cfC.l:alimD :>:h,ips 1~!aSbeen challcm,.gili'l.~, Itl3.ki.l1ig ill. diffic~]I~toO id('lllIliFy chai<tc:I.er. ~1ii'a:1!l~~fo.liiin!ruti:O'f~i.l~ 6am-lypri~:lati'l~"'O~:i.ioo. Am. !~ss~Dia!~Pl'IJli of OIi!l;cha1I!<),

n~t'l

,e!loh.lt:iol1l of Iilile.'>e gro1!IPs ancll jn~8Jdcql.mm \vlthil~ S.C8..,.d~li!l a1fIcl! nen~lOiPlm:8!.

liIypoth~

:ha~:!Jemlp:l'(Iipo:oodl;

(i.),a

~crige]8 to, detennin.e th-ec.lo!lest~'uviflg.!1e~.uive

p:ri'lnates, ,~id~ would fravide 11 brower cWlllexl War lII:Il.d~lllnClin,g p:l'irmlte e'!;lQ~llIlkttl. !DNA. seq~lmnoo and m.o~~olLog,ical studies.
iliKi. ,a.:i'Iiil~ygCll,

si.~D~grOl!lpru!al~l)li$llirn '~tw~t.iJ ~I'Ir!,\l!I1itS and pri~'n1!!Des (9-JJ), (iij 11 si¥re,,"goouprelation..~ip i:eLwool'l rOO~!J,gosilJildprilflli!IJ~ [Prillllill!OBroqiila (.lJ)], and {ii i.)' boJbcQ~.l1'S.os: <LIJdi treesh,le,ws M mD:t.'t t~,iI~e p:1Ii:ntcs I[S1i.Jnd!lllr'lmi8J2. H)J. Mo· (

OOjj.~~oliiEflce shoo.d Ibe' a,ddrE<iiea at .lie LNlpartrrnellt oJ\I'e~ri:1I!ii 'l' !rttegr,u.!l'liE' Bi:oroe IiC~S. c,oUeg,~,01 '1i,fI~1~ii!'@i)' 1V!!H!lr~~!l!~ ,~~I!!Bl~d!~l $(1 en«11 ~~~eri"'5!'Y

"'lio, IlIlhn
M!:!fL!~l

Qif ~am i&te'ltHI!a:i'ii:ic: c:h3:nges,S""IIPi11{lft

locuhu: and :in~ho'IQ~ie.an 5tlJi.ditl':$ ha,,>!,(l;!avo:m

Mlmimi$.t~i!tul!')l'l IBuj!.di'llg~. Ri:I!!!lmI llGJ, i;!!:til~ MM I..ImiW!r~ity" Cdl~9J~ ~~i0ln. lX. n80-~"':53, tHSA. E_·I!Il<lil:
.'Wllllllrptw@![VfIif.I",mU~!!dlJI.

REPORTS
I[~~er, W~

i!!I;;jlOO~d~lw

])NA

~q)\!~~ 5e.QQ!ld!

pl;fl~~(I~.

shl'eW fil1ulli1y, Pti kloeil'C:idae:C21, 22).

from bQiJl!ivi~g ~!wgos and ~e

Wei.de:lltificd

tree

Gir ~m!ioo~~~(;!le~-cQ!!t"i!~t!1g~~OOl-'J
~Q

.30 Clomudidate ]Ildklls i~.ood~ illlg gcmeexom.s. will~ilnl. :Euareh.m~iil. or l~iIlI~, l 04~~ ,L§Xeh.Ild'",-d ~i.1.~ th¢yla<:kOO Aa:nk~i'i,g ~~ul)::l~ [Ilioll w~re lQ~g or ~Q~~it.d ~o!.i:gb f(U'priIller de.sig!!" "'~!',ede!~.!':Il1h~ '1..:0 be 1J!~mti~ :~u.ll!i:1ipoicl-~a!id :s!wqJs~~hi.~ PQtent~aIiy h1· f'(lnUlililive for Pfr.ma1Q1lno!p~1~).j incllels 8h<i!~ U akn.!s !WiSOlHgmnents', or we~ OOI11[l!l!ti!'lio:m!!lly 'by j?irimates end tro!!:!>ilre'Ws: (poN:il~'~i!}'ny i.lj· dl}!:m't1liltodi to beparn!~Ql'l!S gc~e:illigl'l'I~;ltmts (23). The .l!aCk o:f II COhllEO' :gOOomlC!: st'q~~Ii'ICX: ~brmatiw f(Dr eOh.lg>OiS,~iil:!1lii1!8i basal I~~iou
n1C1~r:edp!llyj'iiiCii'liml ohain,~I~io:n (PLR) ai11~
Of

~he ~lIrew geritOl:ll~ scqpCliloo :(23) .. :PC[~.pril1';2r.; 'were designoo. for d,le rellTlilimil~s 1195 cruldldawsl of \\lhjd~ 7:So/~Iii!ru.W:coo a single hru;w:j,in, ruugn. di~l!iflLl:d .illi llli~ f'll!!Jowlnii; ca!~Bgp:ttt~ 32, iitd~lg UW ~~re~ni~;ani' p11i1i.l_~,,~~ufic {81~~. by
oo~U,go<li!'!diOOlli!pari!lml

IflUlie

.Allcr 'exol'udJ~ilgnm~ilIlforma~]\!e lind h}'Per~ vruii.~b~tl iil,d:els (23)iillild: the; ,evall:mtiOf~ of eddi:~Oliml CYI.lmriamagc:rnm~:MliS (mble :S~,), ~~r:oo ir.[i~1R~~~ptl[t~d IhGii~(U~o;ph)lly ·of E\!~h(l!ntii [N4IJP2;.ZNFJ2;, a:md. COCAS (A:tJ. S~ Ito S3)~ @I'(!I

,md !O:4:i~OO1i3; U~ \!i\~ t~.]rnVi,'·~~~!1c (pote!1t~Uy h~fum~i!tivl;l!bf :S~nd"lheria.),

lFlI!J.lL. AlIi 1i!\I\i'lmple !cd aJcodfl'lg ~.eq u:eI11~(!e~:IiI:del~.~IUpportil11 Qltihe .fr:illi1ilatomo~plhaJ ~ypo:tlle~i§. .#It.

TEX2'(!-X(}!I'!'4

~~mu
chimp

~11!t~a_m1Ii!t)ad~ ,~l€liQ.l1 l!i!1~"(I!i! ,q·ou the ~.iQ g;mce i~ lpn~llHI11!t111 ,all 1 IIi1iI~iOlipriirnate 1in;~lg.e~~nd both !clll~9~' gm~a: (sh~id!ed: Qf.ay) b!!!t~fS ilIlb!\eni inl all tJ:li!l:!Shf'L'lWllline\iges antti ~li!t~~rilIl~ O:t;fl!:l!i(l(!ll~'f~I,~ent!~. s:ee:figl$. SI to S:llOllorfulil iIiIlijglil~
Ilinel11itl;;. d'eS(ripOOl1111f lIddffioo!ill alAd o ~ilIPP(Utiililgl ~rld~els ~or ~l!Iiud:mM:l alnt! Pr~liI!Ilrt(lI1flO"lfIii.

ClCliiii!1i1lJttan

Ima.ciul;1ifI mamQ;$el
tfl~(lilr 11u.lsliiillaby mOO~.ll' l!ilmu~

~l~te: i~e enl:etgi:~g rblf~ogC!]ctic OO~~!l!iUS !hill! prill!Olles, colu@os, m~d tlll."e8hrews are a, 1n00IDpf-vyhnic'gmI1l1) (3,.8, 15. 19, ,JUl. No :lI1Gl~ls plaoed.~m.::ws wiJtIil.rodennJ>and Iagrun~l[s (If) or ~!mvs as _1 mlthim. ~1:itm~~Ji'('S !l!H~nmu.vclly Iror ~mBro1lIOi~~a.Ii"Iili'lCiim,phyly): (14).. ~i(I~l1li'fioo ~v~u, i!ld~s il'lllll S!.iPPOI'I~ oolilll~s as 'U~ecl~~t~ivU!l,S; relal!i'i,l'~·of pri!l~ P1'11n3.tGt.I'I!Drpha rPtvUl~latOlH{lrpll.!.'!!: SPBC25, Slli/PDJ., MTUSI. SE EKPPA!E -- ~l(JtS~D.l?iKKPPlRlPQEilliTR Sf:llR.F2, .l'W.JOiJ4, rEX2'. <lnd SSHi2' ~fi~s.1 .n'£! Sr: EkPPA!E-,- -:G:SfDI?l<KPPii'tIPQErGifR. 2: 311.d figs. 84 to S BY)].. By OO'Il1trng~, Ino iIfid\!lS SE~KPMc -- -,rs~i.1~~PFtRfW:'IlIrR iS~.POl1ncd Smld:ail.h.cn8, 1rn;~lUl: iii Jarger umnbcr SE I:KPPA!C:-~ ~i(iI5JCiD.l!'iKKPPiI'tiF'QE'GTR af ·powinl!i.l'lJ~lyil~fom:tilllt~ve 'e3nd~,d3~s l~'<ll'dais: SE: !:KPSA!!i:-,_ -l(;iS~DIPI<KPPiRIPQEIGlTR Il~~lhe''1i!\l Wiar'l'i~ oog:~ .s~ri.~. OI'iC; in~:e~ SE E:I<PPi~~t;:~- ~iCi5E;D,IfiQ.KP~IPQE.'G;rR (A.DD2) Sl!;ppculeda s~~ef"gro1.!rro~!I~Q~I.r" '00LEEKlI!.PA!E::~~~tG!s~Dl?iKKP~IPQ~iGTR LE i!iKtPV,~'"- -i~~DJTiKKPPi9lfQl.r6AR. ·VE:EKlPA!!i: .... -:G\5~D.~l(KPPVJFlQE.iGTR
lWeL'Il t~I!'eW'S

IPtJil1.Iily1ng ~~i!.U·
!i'!O!1ti1Eiim tfMst!!rew

lpenta11 'Irees'hmw

mOO$e
Ir;al:lb~

QI!!q,ea plQI dogl liIoll&e ~ro1Mil bait

and PL'1lIl'l!!l:es (fig. S II). T<JikcrI togeiJihciU', an ~malysi.s Oflllc~e hlst e,i.wllllindc(ls by mlle.<l:llS of a :!>tm~slica~ff3l]lCWO:u:k (7) p;roSEID:KPPA!EREL>GSfO~iKj(.PPi'ilSQ.E'6iTR vides sigl~~:fkl.m:1 SIlIPiPOrt. for PJii:lma(iQlllilOliPllS SEEKPPA:EREPI(i:SIWl1'iKKPPH:SQ~'Gi-R 'TE EKPP,~ EKElrl?'SEDLIKKP~Q:FiQEIGiTK [.P -e 0.0.2:5 (2'3)]. Th~ !~(!!!m!'l'l'yly Qrp,ri!l1amm~ha wa."! i~cI~·, SE E:!(PMEKeL,,y!Se:D:I?K~PSH~Q,EIG;TR pendootly oo:nffinnoo lby pky~ogl;ln~lic~1)!l~ SE E:KPPAJEREl/tSEDPiKJ<PPQlPQE,GilR QmlSisl~ng 1'9 SE i::KPPA!IERE1!GllUlIPIKKPPtillPC!.E,G!m sb:uetronRl]m a ~4;kb ·dati SCi~

cow

sfil'fl<W'

:am1ildil~Q Iljlie;phant.

wid:} l:n1IfiXUIlTWn UkcliJ:LO£Id ((!NIL) 9~A, boatslrnp slIppo:uu]am(l BayllSian. SE ~KPPA~RDUJrVIHllPiKKPPH~QI:IGTR CEIEKPPAiIERELi(J;G!E'[llPiKKPPliIPQE,GlfR (1 !ClOpos~~~or p:rohabll)ly)! 31goridul'ls (Fig;. .2 51:;~I(ILPA!~KE1.!(lAUll?iKKPMlPQE GlTR ~1I~dfig. SI2J Ptrrev~oullly, I!~~hi~[\ebical I'll'tkr S~~KPSA:~R~l.(iiSI[DS!(KPi'~SQ~.IGlrR <II l!Ja~ ba'5e of d1:eE~1~,~J~I~\''iI~ ,d;iO;'LCyll o ~ SE EKPPA!ERE.LAGEDl?ii(KPP- -lEIG:TR ~!\lC wilh confide!lce l~eca~ (lollte!1lflOSEIEKPPlIEKE~E:Dl?iItKPSIPPQEIGiTR
Il'llcie.ar gooe sc~rra:~1I1S

or

or

phY" l~tlQooyIJ,j 1h~ ~er'ofWr waidlolirl1!" With r,edel!lt and Laglln"hr :~i'll'age!i as c:mg;mu~:i. Bril,lIIch ll@ngillils W@ii@ ~st:imD!d lunder 111111 lFS4 IrnJode~. of ~e''llte!!m:e evolutliml!: and the ImE!·'
lFig. ~. A ~grn",\krFJihood l~~~d moWe~l~liH

lPdmakimorpl'la MIn. M, !'II}%:

E!:A'If PiP:~Ul(l

Iflg,&,~
:I: all del., :SIr'1S025 Z ~a dDI';.SMPiLI~ 4 ali! dei'." MliUS1 :l: aa dBI" SHll:R:F:2' 4:!11! del." N;oQ,J!I;,,4,

11111 p.te-mel1lted 1111 the lil!r!lglram MLimO:l.vrWl~ 1'23), lEklotstrap (B.5~ l!alll!~:sal~d1 [Ia,~s.ian ,g:st~llfi:Qr
l~mltlfllsiities {BPiF~): iiill'e sIio'Wrl ail Im.raliuh~fiuwthlclh~h~ '~tm~ ,ne lOO~to ,a1IIcl :1.0. r~e~lI. Amlt~ aim '~ru'inde~ 15n~ ]liI!ierlioo~ ~~, de~etioo) YlIwomng the' mooepi'J,:l!iY ()f E1!!~iid![)!l1m !iHiI~;1?mr.m!i!fl(;!fiI~I'I~1 ,lire l.istred in: 1~il\l1l'ito the' let,. a~!Jft~ With! I~pedj:ve BS and Bli"P '~~ues:. Pi. md.eg::~ftime' .~~~ its, lpr~~d IllIelow the ti1!e: 'ii.?3). The, 9£i@/~ (mi· illmty iliiterva'its (I~ a~E' ~r.wllil ,all rg~ay bars sp,anJilm!;l1 ea~ !i!od~.'TIl@' l~ail11ltesil:iiilil!liJle:S .fimll9~, (ls;rora~l. II!IO~ are preselil1ed.i!1 table Sli.

cklok ap,roach,

i:::::~
110C!tU)

II
I

:1

~-----------------------

Oio;J,Qm,ur A!lil'lJ'l;

iE:ulIrdionllJ
M:Il.BS.92%

liA'r( PiP:; ·U@ InaoRB: 4 !ail del, N4f1J:>2 3 aa 1M.• ZNF12: 1 <1i1 del., C!DCA5

T~
U~~le'

:Pti!1Jcetc~

I "do.'.
$..

::l0

201

MiII~~!!ii ofyeillfS:

REPORTS
{If @!~Qe~r;d]i~~~:5: dw~ %!B; ~~pp<!l!li.i~gSYrn~ihe!"i~ pl~>oo ~ti:~O'! i~gihe Cr~~.coou, L:BA, and ~~mitootlto~,m~ p1~sLadapifuml~ lwl. a IllO'!:K)~~yletk c~~de wid.l Priunatcs, (3), in ool~.t"li'3.Slto, E3:eruxI {Ii), who and gmllll SR1i1lpllimg (25J The mslll~~sfrum our ~pamclllcll~jn set {talbJ.c, 'S2.)oonmJst wilbp.;e.. id\.mtifted plesiRdSipifrnrn:li>as ~m.'1I11~rsof Dcr-vicm,~ slJUdics $ifppol1~ng Su;~c13111eria.\Vlunnl :mopmrn,. wi~ffilin .~l:imalOmrnpnlill. OtIC ireail'llll· )Isis ·of ~~'"&U'i.s~ fh'nU (Jj l!ffiI~U. corls!~at['l~ Ilffi~~ P'!il'w;en;::t'l kn"'li all.t!. lDoih Qn~1!ig(i!st'ii1l~rn ~imDtl<.Jti:f:!;Op~ta (:lii;.1d:~~~. inheMl@ilcl .Bayesi:ll1. ~~ b;;..c()nl~ OO~- !ilQ~oplllly~:yoFE!.ipfi~l(i!l~011p'id i<l,£i~~\5 with the pla_c~TIJe!~~f 1!!!esiaJd~ipiri:l!il1]S o slst:e!\lwilll JaW: g~i~mlic1('U~. 'De i!t1~rice d ~ l,jI,fP:. "()wiili~fas evidelii[.\:V.heni twas !:emove.d: .0!5 Ute sls!~rgro!l1!p loEWI,prim:ates, 1h!~O:l'!gh i~is r:csuh ·is oilll)' w~ly guppanoo (3) (fig..Sl4). fronadte dma SI!.)t; ML trees lacked sig:nilic9li1t bOOmsU'8iPi>lil~~~ :foj' IfiI~c dlivei;g~i~OO Ibei.lNCeU .Allan),. o1lirre$itl:llSii~djC9til: d~al a Gtl!ift ,getKiln1~ ~u£iiJCufIDJII,aOOllll!lgn isail1l1lo.,.~, ff:mequiiti1iIG f,riimaJrul,lfOOSIlli'l.,\V.!!, Mcl ..Mlugo,'l (fig. SI3). 10 .acellf:M~~}' ~OOlh~~t Ih~ m\'C¢s~1 rm!l1~111l A .18i~y,~UM~~ nl1Olt;ClI)I~areIO!l;k :::lp,~ch 'Wilt]) ,-u"i~~.~.sil-.-I"-il'll~~-iilYJat....i 1~'IIfI- (ji..g_"ill ri __ ei;>'" !vSL. C'Q"~_S ~_." __ ".J;; .~(l~j)n:!e (5" of Eu!'l:!tbClllUJogl:~ .u 8&.8 nItUi::u! .)!e!US ago (MY)I !itlilfllilrefl(ip,salild Notp~ E;tlalfC'tmnl:1Iiill ~,7.'9 My. <lllldll"'l'imat0011orpha 1. ~. ·T.\wa ~e:,c. R.Ml'lrsl1alL0.. rMil~ C.. ~ali~, ft 0. i!Ilil.rtin. at 86,,2 My (SIC'C' Fig. 2: a:nd. table S4roli 95% MiJJJfe41.6, '1:26 ,t~OOl c;redibni~y in~c;rvaJls')I. O.lilf d.i'!.l\l)iltg:eit(!l;l !lm:r.::sfor d ,~. !E. J. Smgi!; .ti'm-rn;e 2:9'8., 1'5,6,4 (200,1) .. HOfiltl.ll'IOidel'llCcrtPpidliooJdLla (16.:8 .M;Y), .A'I~d:UQ .. s, II. I. Bloch. ~. T. SilcQ~" 11).~. B~lr, iE. J. S;a~:5, fifIX. l'!!"lni. 41:00. ~:i. .u:SA. 1!)~, us'! ti!OOf;l]l. ~Ldea (4~.7 My), f~lnu!"!Mi(;:nJ('rtlm .. {4.o.4l My}, 'i .~. ~, (j,~i!II, l ~, (i~~~!l, D. E.iM,ldlM!iI. ~~.1Ild.l: Slrt1psirhi!~1 (62.1 My), ..1.Iind Primal~ (79.6 My) r;e.rteJ. 2:11,.511 moos). were '\\lezysimiiaii ~o dIose esl~~~b1L~e:d fro!M:an :im,. s, IE" i?lli1fi1i~~ .~.fM~ 3lffi •. 2::lI.8 (2.oon dcp~cll'm .S9..7~b .:lI~igtlmcn.t" J lhe CrrRgare o ,6. w. ~. M~rplill' ill! 111, Sdl1J\lC1?:l:9~" ~~B (;l0lli).. ~llgio:1l (2,rij, (lah~Ll:S4).TIm ra:picl dhrergoooo 7. P. ~ W,Hlcr~lJ, It ~1!i'l1Uw.IR. '01<1,G.!loll~~J'if.l),ml:. 12, ][4·[ t201l1:). aemssihe basal cuarehoiiltm 1l00cl;; cNplaililS why; B. II. 0 .. Krill:g~ ,G, 'OIIWr.lkD'\l;~ . .hlrt:~,1. !Ir·e5l111li,1 ~Sdlmitt d~ilc dm sc:ven t[ldl:e1.Si high Iboolfl:~nlp' ad oocli lreROJGef.ieL ~3, :lSlI(2!l~m. BlIy~~u;;]!:l :supPQ:ilI·or rriml!);lo!]lo:rpba, W~ w~re f ,~. "= .1), Mi1irti!!, ?r;'rn~ QrigiM ~mif~,rut:~ ~~!!.~I!.!I If!{Jt able: to ~ed ~hc:Sl!riclaUlirria byp)!'e.~~~O!!l Om\l'. I>A!~~, rlJlr~lil1\. I~.I, 199m, P
Q!:j,c(;li~g:i¥e~~!~Qe
"o;JI,!

li? P.. ~.W:ld,ooll, !i. SIi£alt!~. M.oL f'hyI.lI\;It-n£1" fw~.2:e. 191 • tilOO'). . :lCa. J.S,dhmil~,. ht (llllllfl, !'I. $uryobr'Oto, Hr. Zlooll~~f, • tr!a.I. SJiJ;i f~. :l:9.2.~(l3 'l2iOOOl.
~9'. '0. M~~~~

~rOf •• f\falwe

4@9.610 (~~:O:U,

~3. S<!:!I1' ~~!!'PI1I!1ifl~J f~~lert!<!l~~ 5(.iffi:~ O~~. 2:~, I!), !fllJt~m eUI'J~~c Nalt. ~I!I: S;d, ·!.IS.,A:, l@A. ;!~'!i'S
(2007),

~iJl.W.}. M4!I~Y~~ aI.•, li'4t,we.::iril'!il, (:!lOOll. ~l~ 21 .. M. C M(I!:i!Bna,. '5,. Ie Se'lk ,~~wa.~oo'ol Mam.J1Ii'iIll: .!ib_ 'Ii!:>~~~ 1£1181 (a.IUi"lID!.li iJliili...." ~~!!!.!l, ti.i~ y~,k. 1'l'9'l). 22. K. M. H@lI~1'I1 .iWa.!l'JJ'OOI' ~ej ill ~'lJu~ ~'l\Md. Ill. E.Wilsliin, 0 .. Mo, j;L~r. Edi•.~l:ol!ll liI.rm I.Irrriv .. Pr'~~~8~~ !MIT:, ~ •. :woo), ~r:t.l.O~lOO.

2~5.M. ~. S:pfl ~:r.! W" .1. M~.fp·ll)', It.. £lfh1'k. :~.. ~.. Q'8,ri~, h<J€" M!j( Arud. Srf..Us.tt 100, 100,6 (200~}. ~6\ M. ~.Si~eiiper. N. ~. YQurnq, aL P1\fI'Ogfnet. frui.<l.l. M
!l:1M t.1:00iM.

1!lti!e basis of se~Uet~ dm41<lifone :(Sh~~lm<!iim~ Hasegaw.1li ~:cst.!P"" O'J}66) (23) ..\Vc d_idrejccI an alliaacc of 1:W'C:c.s:1iuuws:lmd. I?rilutcs ,(P ""- Om1)\ dG:Spilfl the SilI:'lg1~ dl~sc~pa~tirndc1 :!luppommg [lnn~3~ + l~ ~hUi(_"'\\lg, l1~is (I~~a'tiO:ili i8 ~~ill:i~ ilali' :~o olherli!l1Id1irngs (lir~Qool~pilcre ~:i!lT!~e 8(utial,g
]1!1{he OO!Mlnor! O1nceswr of

nco •. M..~" Nij"a~eIi:,ffltjilJIJ:

12. U.

n.

seqlll£'noes fromp.tilcl!cien:id Il:roe.sJilrews >fIUt'll~1iteds to d,aw u l~iI'I~ origin. of e'x!!:aI~1 ~!l"oos:hrn'l'o'S {Scandtmlia) to ~63A My (Fig.. 2 ;,lndU!M~ 'S41 In,~ lIte llit<lCOOiJJS·'"[:-e.!1l:iau;y bound~;. OO!'iOO!lllMln\'o~rnh

Cl!ilJrlenrnl cllades (n, ,28). l'he ~,llOlmion of iall!ldenrgcrlID

mp:~dly divclSifyf"s.

u.
1) •.

16.

186, .liH n<)~}. II..SM~I~aJ'~ !it. ,(. Md(i!rnIlia,i\'Ii7l, null~i!'Mlr-~1. 9, . §n (Jl9'9'S). ~. ·C. el'ard; in' M~ Ph;)1~PfMffifm.~, iF. s mi::!t. i!.I!..~. Nb'i'.l~~ ,M. '(.Md(el!l(:!.il\ f.dIs:. ~s:pri*r. NEW 'rork; l!9'')3), !!f;l. l'~l'.!O. IE~1SOil'gi:5,E~l ~~{t~·l3.i ss (,2'00<11. 1'.'6. R:.Liil f;!J M~ 5(ii!!fJ(~Z'!il1 17~ f2oo,:o1, M.. S.5pn~(, m ). Slalfltl!:lptl', 0, l'J.tlil:sl!l"I, 110'.W. ~ ~~~I'!lI, l.ll:!n.(;i:! fta[ f~ ..19: .:110 '[~l It Ill, i!'\dMfi!, ~ l b~.!ifiJl1;'1i'X. lIknlt J1€J!I'i:.I. 5(/. U.SJi f 88, :llOO.lf jI<J!9'n).

~:7 H. ~jililioora. M. !!~qawlll No 'Oi<ad:l.\ PffX •. N{fll. Acoo..Sd. .. a.ll 103,W,:J.9 12.~. ,:al 'IN. J. Mv~y,.'l'. ii. !i'nngli.e,r. frider. M. :S,Spl'ing~r. 'IN, ~i~!~r, (l~~ ~q, ~:l'. 4!!3 r~001). 29', ~. Hl. EI!!imIH!£, ~~ A tieM SNiJy()1 BlNnml! l~ee 5hrem (UI1II,o.of C.a!IJlllIfiar PMS~,.B~fkl~"Y' ell. Loom . j 0. TIftI~ rn:lF~ mU Slilfip!itt.@l!llirn p.afllloj i1~ (gram!!! EN:J62 M49! toWJ,M, .!Il:r1 EF0629S:60 ID iM.s.:SJ BOO' Ill!!! tl<1i1ftiMl II1j!'itutt$ Iff He<llth ~''!Il<I!ll:iI«lO,:!2~.Elt~!l'i'.M.). We tl:liill!!; flI_lki!ni~gr, l, (ri!Hil, II.. Wil~,fSDI1\, V. 0l!1lid, K'. !)lIIrki·'1I. I!). 'lmll!1lrJ" lG!~'Ir1!~imir .• .aM II.. WW~~ b~et:!:!lTrit<ll ~rM~i;!!'!!!~iJ!p,l"!In .~!iI!!t~ Bf,l).!!d l!rllitlU.!~MIa~~cl1.~~ IlI!:iJtut!!!If l~~dDfi, ~1mF; Oll!i!gi! ,~rlill!if"lCilif!.o!:li:i!1Dil ! GeMfIll! Seqlle fioIli i1I1i ,Ulllt-et.l!luil Wa!lliflglllmlllrilvenlLy G!!Mifi!! ~@!:jIJ~;i'oili[til '~i1l1!' ·rtir ~(a!~ .tI!l. iI~p'tIln~tt@d1 ~~IJI1fl(@ dl:.!i. $~Il!i rrom ~11~ '1!i~di1 mi,@ tt~1l ,~~~d [II ~I3B~1i w.n • .ilm~II'~ii\ iilLlI~bt!lf5 W1421,ljo. E:Ull'l22~·JL alii!! 1E!J2BOO2-EJJl2'BO],9'. SupipDiltingi OIll'UiIll!! .M8Iti!riilll
_,.9fI~:rIll~r:fia'Y!~~~ilIiI.@rlllitllltij.lel$a'j.ln92IDCi ..

.Mlltl'fllll~ jll"l~ Ml!tMd~ figs. S;1 l'!]S14 TabLes S:l: ta' 55

~~r,ell!t~;i.

9 Jrutr .20[)~; <i(;@pl&lli O(toll~r 2007 1!O.11::!~Jsd@rlf@:lM~55

divcrgC!'liCC e~:ID~n'ltcs.of !JH<my CI!!tl.1CriaJt ome>l'S and cmlSi sUmt\'Io'idl the lG1~g"lllJ.lSe lllooQl of ClII.'" 1~~lerifl,1fI.dti\lQi"1!i[jrotIDn (15). l1d$ d~cp dJ'IIIGIl}ooCC
b~\W~l
P:lili:Ultf;JUl.'1!

comopliem:e!l1ISp:roibl!md

ioral

!lInd olh.(lll" SC8!Uldm~tcl'l:i'ts ~wla~:omealaUlcl IOeha::...-

dil&tii!~~~O:U1S Il",ve 1J~_t

bceu

dO;i;;,.mler!l~

be-

~'I'\Il;;erl. Ih~gl!\]lIIlfS (2,U. :2 J, 29'}<w!di vindJ.c<!i!e:'l INCc.nl ·c1.<t58il1cartions d~.. :~Qave selhl~ Plt~ Oll'l't,'iM';in. aun~lJe faB~ily. Pti~oo~.daJ::' (21, J1]. As lfilm sale: l:ivhlg 1~&"iCin.ttldw of a. w91£rian ~~n.t'l.~~ dJ.\~~oo. hili ihe ~:~y Teruai)'i!lloog IllilaJl wl~.mai!l!Y m::xie:m. mammal ian.rude:~, we ::rugp. d~<l!!ih~ :p!~y~"Qge!1e~l;l;mjqlllmcss. ·Qf PI!. ce.1~iM·, OQJ~'ili!l~dlVi,~th re-siriclq,mll!O 19~?iIO!ncl i~ fGresi Imbilais Wllthgll a ~latively Ug~~iiecil: gl.Oba~

.A Genie IRellgullratory Netw',ork, ,Sulbclircuit: IDr'ives a OYlnami'c Pa,'HiB'.rn. 01 IGlenls Exp!ressilon

Ea.rlyspecification .of elildomeJloderlil1l8l~emitcrie:5 ilmtille :sea IlIIuhilil emb~ ,depenid& ,on <31moving rufUS lof reg!Ul~v 'ge!1!e' ,~~5iO'IiI, Wi~ show h'OWlhii: dYli!<lUli!ic pl3l~miJi!!1 ~UflL!iCl[!J~ enrod~d 'in a g:ene J,~tlli!.t(l(!C!f fI~fk (GIR:fi,I)s.!J!'bdn::.~it th!'!~~m::l~d~~h~{I~, ~m$,.a!ildblimp:1, g~!II~j~h~d~f\:l!Ji!:~~t!:)!y

runge, shcmM :ro~d'cr it animportru.l[OOilSCN9tionr ~rnolity ingroba.100l1leXl

lB~!jse our(lomd~ia.l\!liru~lPly

Illilr::lll. oo!.lIIg~

,~Whid;) ha,'I,1~all boo!:! @;i~dmI\'lMalily defii!l!~d,A d~;il!lawfY r~oo~mcr;too '~l(perimeirt: re\Ile-a'~mtha.t ,{;limp], .ilili!JID'r:epr,~mc'~·a'Wlurm rolr p'egms'lilj~' e;i(ll!iiCliIJ:1iI ofl!xprre5~Oi1 iln the ,oont~ of llie tGl'LJ),5;, vdfIe'ri~il m. oiL!ltwiiro exPill15l00 'fdUeM reoeptiolli 'oit '[h~W!iit8 Iig.alri!!l by .ilidjilQent 1(:eII~!l;.6,R1N cirtu1bylmms 110mrOllli;i only ~trtk :5i~atia~~S5igIIlUir'i~ntill de1l'e~oprnllmt IllDut11.00 dY,lIlf1lmK IIiiOt ~egld.atCi,ny paJIJlEming! .. 'oontJ'i)l sys~
!'!egC!ilO!i~iC regulatory I;lod~ llIia!! ~!1tro!s Ihe specifica~ioll ,of the fuwlre Silrel.ew" genio. ,gut endxfotl'll,~ndI10nsk~j]eto.g,eiI'lic mruiooer:anal OO:I~lpo'n~~ts of 1I~c; Slea. l!ai;hin 'L'l:it1Jbryo is mmhodioo.in, ~ .r,m!L~ro~i!i~!lII}:i'jI' mel·

.IiiJP:Profor PriaT!~es in glll!dly i!~g the ev:ollllkiAm ofadiilt)I~v:e tri.'li~l.5,du::se !ltesIJI!ltslllay ,dfed the placement Of'iillW·dilol!llnn .fossi.is.i11llcl.
tI.1IllL1~ tr,~~~~:I'(lW.~.! 1U~
i~ih~It'bQ~

miller p'ria~lii

Oi:ll'gl'OUJp'

(!I'M lILIillclcrstaild:iull!; ofpli'imam ~nml1~ccvo'hJlltml, (3-5) For ,(lXafl'lple,!I mOO.i"llillilO~lO~agjea.l ana!l~

wmi {GRN). l'ihe GltN !ll<Jlesi~hei!1'!kfaotiof'IS of Oloout 50 g.enes moodiltg, O:"IlSCripttol'lfacto:m,,'<iS dehmni~ed. in a!llle:xlensivepmuroali!ilI!l~Il<llysJs along '\?iI'ilh ath~r data (1., .2). 'il"he stlbcireUlilS of Ilbiill nL:itw'o~. cCliltrol. Ith~ estahlishiilleiftl of Iraill.-

REPORTS
!l~,;~ej{7}. .By fifi:hc!,eaY<lge', ~iIi!e l!rm8 g~!'I!e is .m!lh1ate<iin lhefll~.cimm.cfes (fig,. ~. neC). iCl.'!ll1!lC .~.C3:lirnliwrrCF :find .Blimp 1 am tim rCKIIlU-M illPU,js :i~to lhe lw.r,~8 gefl,~,~~:M£ma~. .m.~.i.Ylif~,]fael!C]r tij.~1 be avai.liilb~,~,oa'IIc'li~t~l n "viOl 1I1e ~vid¢nc!L',i Iilii:lll! I.lli!i~,g:~'~ L"lli1iit~i1l'H'I~:~y e~p.!esse~ (fig. SM.).. '~e~l d'l,~!~NtR gene: bc,ghllS ro be tf<!!'I.~cibecll, its ~'s:pQnse LQ Hs own s;igmIl lr9!~ oo,l'Lcl·k~:liIsrYsten:l p:Iloomms I!i, pos:iljv'lll foodback: ei.rcuit: beilwL~~Dl acljmmil1ll ej~d'alm~oocn'i'lal eells illst '~th, jproollJoo ru.'id r~~ivi!) W!:I~S. (1 • .fj, Otx: p~'ll';in.i~1I1"(li rllJ,qcl~ri~dl hliil!i;a]~Jim!~l~e~l1:icro~lere~ l caw]y :Uri! cl~vag.e va)',I~en.ee it is !lv.ailabl,e abini6o. blimp'; rml!lScrip~ii,)n~s ootlv.a:re>d ,ml!ec~eavage 9ilile~' u!1.It8 lmi.1SCriptiQU (Fig:. 1C and mg, 8:211.). A<l1l:iv!uion :mll.'i.tdepend OI~ lil.'c GnJ~8JI\'COO l~vc~ ·of l~im~W:Il!iI1l/TCl? lalpl!lt d,riVCl~ bly \1~m·8 ~:~'itli(: dOl,'[J,aill .aoo. th¢l~ ·~Il.he m;CSiOOe"~~ ' i'1~lIit. llid],iWOOwil~S: 00 ~k~.s.ula~ory W).@).Y'· tr~"il$cviW1ti(l",i~~lf. o.lI~e boU~ .~~Oies !!.~ fraHW i!~ d'!csa!me oeils (ie.., fwom sl,XII1I~ doml!tin. sis, is ob~~g<1I~rO:!' blimp! ex:!l!res!iliQ~ (tlb!~ ~bcd S]). Thllls,MA:SO I~cpress[co!] ef Wn~8 'l!Xprc£" cl,cav<\ge (!Iu), tire ~bci:fOOit aro:hi~du!le (F:lSlIlc:termmaN~!!l(lf theGRNlII!Kk"Ji~yi!!£ endQ1JiI!(,,':SQ(!erI'WIl'ldLcl\.~'lopnleil:lin ille sea. tlro~ilin skln celi~l1inate-5 80 I~O 98% of cnJiy b.limp} 113) inrn:ic'ff!Cs lIml the patterns of c·l(~l!CSsion of (ng, 81), c:rl'lbryo (/, 1) has lrovcaled dmJI InI~c;:lmjl' ,clJ:!'!,I\cr ,(l:X~i(!il the ilil1l1llid re&tJi~ato:ryp9JII1Ci1S., bUml)l aed of Ilmm dynam1e rerus ~Ia~mmn lI.wGRN .stlb~ is Hl.~tl"[JCSiOtllli()n.IllMStm:lflroC:i1ItS of Mim.p 1 '1wtt8, shm:nid be .!!il1'li~8r,.T.h,L~ w3£cxml1li111\'!<! circuit !lho\~\JQ. FiR, ]R To !lt11ldernUllidlih~ mRNA. by qIll9rnt~~lltive r·M~-lim~lltlor~cooc~ i:rn. by \~holc-:l:tto!llJlill in SiliJi.ltI.ybilirn:i:zaI:ioo.(W~~1JSH) '·Un~er.:lr-; thail] r eaco:. ,,8,. -'" A· and ._. • "t!i11 "fi'_ S:'l .._ _ !E3:) (il'pe'!;,HioR ,(1f tI~L!'I.s,~bd.fC",.it, it isillll,JO(rtamt to (f~g. [C)~ .mdl d:~rpalte:!'!ll~ of ~p~,,~(I!,! .~ !XI!!,. _.~ .. . MQ\.Y thata sm<lir~alti;own ·of blimpi mRNA is ~w[ly~~n1cdl :ii!'! FtS. '~A. M essen!!1!1demgl'l.fu<l!u!:e o.f t~ijerele'i,l'mt present m<lltef!1"!lIy~lm'We:ver. I!'hero I:S no. :1'11"" [ili ... ~il!flo~ aqrO~-09Y" :15 6-29, CO!~f9m~<! i!'!~~.it!.!tt·~J ~ l@Jjllfll WiltS' :mn:RNA. ]I~ thc:carJ.y-c4mVilg.c:: blimp.! cis =.rog;liIatory InOO.tdc is tlmt i~.imlcloocs Te~liin(!O~lI, P~:(!Ieno'!\ {A 9l!.H5. UlSA. 10 the iI1Il.Icil(;'llI:s., 3l!1tfil'iCiJlrcssi:OOl silrcs {S}.Ibe;]ludllillOC.tW'C of H1(:: "''I'D t~IitOIIi1 oonr!!slllOlII~J!lQ!' :5:hmj[d D!! <l<ddr@55Eid',I~·mail: .emb.ryo, p.catenin [oc;]Ilizc£ dali'i·d!iQn@QlIl@(:ITl,·i!d1ll and by rm~rtb druav!lgc, .~~U!:nIIl em'! IlOO !l1lL'bell'cUiil ill Fig,. I B slImt!sts HlJat 8iulnroprcs--

mwws gf l:m(h wmB .me! blimp} f~!1ClilQ1Tl M A.ND OiPI~:mlDl:'S 0); dli1lt is" 'I,vt.l.f8 ex~f\essi(Jn ~requ.ir'es bo:lllil ~,.catGlliIJJICf and, B~~lnpl in· ]lll~q (4) amtd! blitl.lfJl cx,p~ltiSsi.(ln reqlliilliCs bodl ~Cl.1l~!~.il~rrcf ili~c:I Olii: ~ti~i.u!l; ,(I:tlJb!e SQ. MQrph~lino-5~bs(ih:i!~~d ;'i~ti~¢1]S~ o~:igQli'!!J'. cliooaide (tvJlAOO) i~~~!Qg blimpl!llRNA (5) c~ro,lneres" n~esc -celb giverise l'O ~lliIek'Cle:!o~ Of w,lt$ mRNA(4) s Mocb e!~do!]1esodet!]1 g:~11ic HiIle.!iitles: of the ,embryo. l'mlllsQ,\pitimii of ~jfiealkm. 1~1h~ CcilLd!esttmm ~cn!;l'; ;!>Iarts :M <%0011.11 6 booltS E."'p:!I~nCl,f th~wm8' gcttL'iili1iL15~ tho aRe:i" f~ffi1i2alni!oi1. Il.blCDl,ill{Km,sto the!ldjaeein,( C9i'J}j~i.CilIIOill~ pa;OCCi'i1am:! d~,rnct]y OOn.lm,IS ins I~~~ of m~d~~I3J~ b~"UJiI!tt'l~II'eS: ~J'I d~ ~arly ,~pal~on. S(w~~~clJifffi~l'l~ U'/iM~~~ ;~ ~ . : .."'. (4\ AU!til(]l bl"'styl<l!5iI;~Ale (]2 I~~~, ould fi'~<'lily 'OOC:O!l1~ ~cm""'y,il'l 1:11"!'l IL ... il:.. ,.. G:._!)IO_ \.".f". ""_~iI>" ",1,1 ...... ;!:ll!ltliliml 'l'lili; f~~es (he ~:rec~!'SOroells Ilhal wUlgemefa!te the 'ear~ier evidence 'fr,om sea l!Ireh~!l and XOl0l-HiS gut jllsl be:b!;! 111JeSlc.l!ldhynl,e b,IM~l,d,alSt'lge (>~, 8 indica!leCi t!I~~1Wing lsp.!'ooob1y rrespmlSible for ~OOil'l» (Fig. 1A). HOW'evi(;\~~ r~~lin w a.fu.w boom> dfi,v~ng prQgrcui,w ~~~eniln nIllGl~@1i.rza~i(lU af~rn" these g.cltCS: are first 901:iv,:lIItc!d~their dliIring .eI~v8@c p~, \W [oUlne! d~MWit~:8 is exprGS:siOIl is m:~i"gui:sll(;ld, Ilr.slil:1J IilrllLl: k:c:1~I0~ ~liLo;;ibl!1.'l oorp,mdtle~ng s tln.C' ~!~i1IillfTCF

~~g!11tl!iI:~I;l!~~ ~Ul_~i~dl~1l\p;:lli<!1 QlQ:!ll"i!i!.'ii ~Ii!e,d:e''\Iel.Q(.!il~g '~rlocyQ. HeN weoo!15ider a GRN Sl.Ibciroult, themlll;cliQ:1,l of w~lid~. to is direet a. dY.llfilll~iM~~y !"ipOildilThgring Of toms; of U ~~.gatllffJJmr.lr'·goo;(J lnJ'ru:t';cri.p1!.i\t::lIl mtrlyilfi. S~ uirlli:n, cl~~b~O!'i,¢Ii.~t$,Tr3ilHlcriptiO:il {iif the l:Oru~ ~SIJjI(iJOO!)'ge!1lM be!llilii~<'lit the vC;~1a1 ipofu ,of' 1~lIlieegg Ii!'! the pe,.'lyoo!l!1 fuul!ilih"'C ~eav~ge!'lli~

~r

·!~9~g tb

..t~l!~

ci~I.,~g1lJ!1~1,lI;l)wy ~Q~!;!lO~<lP:Plio·

¥~s~,,~,i.~~d in the!!!.ew~jI' bQ!M~l~crome~

A@_'
Oe-alolagef 'ead\!' Iblas!ula,

Ob:

IBlimp~b ll"caI:~h:! dea.:lia!!lm, th!l!

IFlig. t, MmrifilgJ"OOHg'5 Q,rme J!ll!(WI'rl!!:ssl~~p~m;fH~.. ,lId Jl:~IW!r~sJ!lfilrt.atigf! ,(;I,f e~l!lriru~olil patte,rlrl cff biimplor wn:~8QI!mes hE!dI'. Ih Ii! 1I1l.rl.enlIl:D.st (!eII~salre ~1k!e!letll<£lellli,iC m~:[jmlll1le'~es.; ~liHl Irml lrim.gl 'im,frle sl1!i(onddwawi mg~now:s mes(ld~'ml'li!'1)~1ls (pro~~~ml\l'1'l si'1ooliida.ry me5i'1!i'1~lny,j;'ii!II'I}';II,~ oillJt~~ ring ils. dffiillnm,ve e·lildoGl'lrrlll, Bi:pressnolil' offttae blimpl. gelil@ ib!!ginsil'l ~ltJe IrillIi~J'1Of1iIer€~5 ,i:lrG:l'I!md 6 h01ll11!5 artelrr[ieritJiilm.rticl'llIi!1lll1al iI.ppei!lr:511i1.the i!ld~ia(ell.t ti.erof f'III~l)d~~mi1!l~ (€Us b:y12 hQI.I!I'$, SOOIl gift~lI. e-XP~:S51;(lIii' dI~lpp~ars. :rlltllTil the ml~no:rner,e:s. By IS hClu[s. e~pll!5S~Qlllcf blimpl beg:~m[1IfJ ~bii!: illC]:<I.cent IJf,E:SI!IllI'1lptive e.llIdbderm lineoage· amd aliSa1~ars. filloin the mesod:emnaL rC~lls, (Bl GR~ sl!!li!cir·cyit il!f!clluding QIxs blfmlXJ, .• i!lI!dl wrrtQ g§:,f!es; .tiimp<lb lilldliwte'.s the eiim~ iso;foflTII M the blimpJ. ,geiiie (5); r1o.:TClPr COOijiPlex of liii.u::leiilf ,~,-(d,tenlll1 iilmd TClF trarascrip1Iicmfa.l@i:or;· 651<3, ellll'Ylll'le .rnCl(ml!lili1!.Ily .spornsiblefoo m

rmptietl oflhe

~i"~·IiI~ilil.r al Gmllldi1WTCF @omple\i: fa·.rllflll"in~1!e\1ldl'tt2) an:di:lel1s: as a dllm]l1Iil1rnt 111ep'.ffi~!lOr .art

WIiI,tS S'igmfij~liglilnd.llithe- awence

amwity

'gi 1!'Ihkh is 'i!llhibitoo

e,f liiud~~lriZiid

i!:; i!

c·~S:ll:qyef!(!'l of

rmiiG ~iJrIiI1ing by GSK3.,th!! :blO;dltJelll1~l:iIllfI1emmi~m! of Miich is; !lYi.slued hV th~ !\',Ciiii.dl did!!' •. Pm,m'll,e impllts iOO'l B~rrnplalrild IllIb·],CF mntm'l .Lt'l!.m ~rallil~!n1mOfl (4). Wilillll~ilS. ootlntlilb"T(Fi1!n:d 1Qb:[!f'{! ffl'~,Yiroci if~r biimp1 e:~JiI!r'e:Sll~OO~ blbp.l is $ubjedtc aJll,BeiJfeSSiorl \ilfi twcJ, BU[JiJpltarget:sites. ('() Ilhrpr,eS'SiolllOfMt8 and iirimp1:, v1MilIl~'Zed by W.MIS.IfI. BVIii~ffitl1ide~wge" ,~1'11.8 ~f.i!IIi'l~I~ b ~d~t f'!i1!h~ ~(!!!!~mtOllom:ef~ at ttl!'! ~leJial, pghil', anI!!: d~a!;l~ la,ter (si:dlii),.l)l'impl tranooriiipts !Iii r,1i!Ipr'l!Slenrllii'l1ifle mi( r,ti(l'ie~ After thl~."'NJ'8 al!!ldl blimptl 1!'rll! eli:pre'll:edi in~liIe Sdlml! lDemimrie5.

bath ·lIe wlflt8 an<i btimpllh)cit (dg:j: bhle Iba~~,~d ~sl nibefCF is: in'nlbil1ld ~

REPORTS
~~Q~

9!f ii.he bNI~p!' g~n~,. oon~~ It!~yl'¥ i!:!le:r i~

~fe IProg~ive ELlfIdiwI!18 tr;msc:ripls

<l,c!i\'~tiQ!1,. QQ1!!~daocoun~ b

eleaeance of both Mmp.l frolli. thc: oe~ror of l!Il.e .OOl,'lng :Iotrtl!; of regJ.a" iatoi'}!' g('}ijl~ trnnscrillltkuil. .11. series of cis~~~Ia!!NY~eii'l£i,i.¢~~'~,!i: ~j(I1;i~i'~i[i(int!il~lfIow~cl!

\'Jkm .~~ e;!{p~ri.n:!~l1t1i!1 ,~mbryg:;; ,~~g!~~~r~dtl;l ,ex~ blimpJ l~l!11e ~neslXleml (Fig, 2C, mnl} ruldlifih oo!unlus). [See (.Il)! al1l.d.~g. 83 for qlW1limll'l,'@ dH~8J frolt'l 1iiIC$e ,c;xpcriilll:l0nls,.~reill.d" in® 8uGiilh~cll (iFfiriRNA .Q1!IlpMt ~'rum the
~'L';I~J8 lBiAC-GFP

''f!~~~e¢)I>p~l!tI!~t~
progressjve\~

OOI:L~C~~]

rl:hi.~ i5 il'l:d.oo~~.~JI} !:ru~ltan:i$ml of ,el~at.tnm. We used ..~ htl~i~p} eDNA (".XJjressku'!cO!,"5mict l!ffiiaJ~ lPood.uces m!olin.d blirJ/ptmRNA under
1!1Ei:3!~
OOl~Iro~ ofd1ecis"i~uJalOli)'llr1.od:Ule

Ii"eSpons1.blle

Aooolicl;~f:igt.o dl~ ~fCi~it~o!lIl~of Ute ii~b· ci:!;;;yi't ill Fig, I B,!X'-siU''¢spalfal ilipid. mlo ai~ bli'mpig£ne is:pmvided by j3,.c;ate!iJiioffCf (i.e.. in, ~IiISIC te WillS. sl~rmnI1lg)1 beeaase [he

f'Ortl'.2lily Mmp.1 ,expressl<m {5}1 (F~ 2. A sud B), WI~!.::ll 'i1IDe~IN;'Cgula;D:tuy ailJt{i!:~rcs.s.io:n shes w~~ lIliuUl~~ ('&l'~S,.2.13),. lli~ CO.l'Isnro.Cl pmdu~ fiMclu~ of :!I,!~"~;;1;l blfJu/'Zlrn.n9Oripl Iyva,al:
wid~in IllIi!e endog~nO'Us (lI!1esod.e!'nl!lI.~,blim.p1 c1.earrnll£C zone,. \!!i&!ereM .he l.":Qntrol gCl'ler.lI_ed orn'ly the IllOf'lMlIIOru.s pat!~l of C',xnflll.."'lSkun. (fig. 2C,liffi'Slt.lllJi'Ci2 oolulmLt!l). W~ ~. tln.csc: coin!"

1Pr:G.d~.ctoo. emrlp[c Wil-<: .s~'rnciMt I~Q cause co!Ui.nuccdi:e'Ji:p~siQ:!1 ·of wmS i !~ :nleoodem:Jil~'Ie~tnries. lEudogeumJls wl'l!5i'ge!te
~O:'iU~S 00, lru;l \~.e1l~er,iI~~

lrodbp~l~nt

(JIr bliIJJ()i,!nRN'A

{l'x.pression nlQlllj~Qred. byW:MJSH, as wdl .iIS. a (!Oi~jOOtccl.l~1~t8BACdGf'lP (bae~nl arifiCrlal CIlil'{im.at;rnlli~gI·C!m, niI)J.OJi'C:SOOlt~ proluill)b~ock-in. lucpillrtcr, ~ijeOOpefl>iSlmlt Il!Ib....ooml1llal c:.:prosf1i~g... .Z... 1~::<p~ril!lil'efl1!all d~mOj!tl1rntiOfil ,~fspalliia!l bJImp]. ,[lYil:lOr~pre:ssi.OI1!.

produces lID!'eaclive ~-ca1~li!lirCF' IIrot!!LQiU~lio!a fOO1Jor OOI'Wm~~C~ i!J'!a:~isr«JlIIjrodi forel\:pre.'\S~on Oir Illc .. w~t8 i!ilCI1~iml,cl[ 1111 'dUo'!' elldmlfl!\\SOOel:'i'nI, TInereftill:e, ItEm restriell.'ld. pa1l:GIiiIl. of 'CIi~d:OJge~o:I!I.s 'JI!ilmdlcj"rn;·~1.~I.lfilmre is:il~o 2111 91~Looa:~Dm tlO:IU.. ~t(millffCF, due 1:0 d.tL:ll':~ctGdI. dcaltlail} crf pLllwnl:, adjaec;lut Ci2Us.::tre illd~L:;d~illl\1oo.lllroU€';h WIi!IZ exP~s.i(l!ili sufJlc~ f,0J( 1iliI,t': I'l!sl:ri.Q'N~d U~j;s~i~n!ll-dicive!1 'mmm;cci,IliQIl l,ocF> [Ute ·'to:m-. ~!!!!i,a!I'r!X'po!~io!~ of !he bJi'rJ'rpJ ~em~~Blilt wl1m m~!]1!)' 'e:rr~cl" Tire ,i;:is-re~I~rof)'ily8'te:~l dH~reslrilJt~m~ ·of Wmg C:l!I}!le8..<tio:ni!~"e mesa' of I!l~'ewm'8 :g.enc operates as .1In ANI!} pro~ s.m;iWl. (he SetlSC, d~al it feiitlires !oolffil.d:Le denn wasre!all:iOO. by illlrOO!!ImiQu of 'IXltopic blimp.! muRN}., Ilhc: Ill':Pi"ffiS;iOlil.·ofdle b.limp} ]3~~nl!pland .~eaten:iUlJTCl'll:lp'l!1t$ for fimmiOOl. 1111!.l.S, thill :roqll!lirmnl.'lUnfor Blinllp'] Iid:lkSiit GFP oon.SIrttCt ~addlil~ BHLlIlp.~. IlarrgGI siites was am rnll3l%oo. (Fig.. Ie,. :siKlh calumn, bottom), ~blQ.galO;rily In ~~e:.sooooo. foo,db8:ckloop .. The:

otb~r POSiliV\ciIl11Jl1lJl.t, Ot'l, is oo~ti.n'l!l.oos.ty aV9!~lfiblc Ilhrotl,gh.mltt Ihe 'wilrlQ~~ :i'L'gio:n.TOIW;~ i1)!Us,\.\I~ I~ooa bli:mlJ! (iFP ~(lI1~[ beawin~ !llUlatoo Blimpl !a;i'g,~~ ~i~. 1Jil~i$ e~1~1nICi~ crumo:! I1UtO~~res~. ~U~.il ,dL'IJ!htYSili Jn~nal paUer:n of ,e:x:preSSLQ!l if lhe loo.atiOl~oF bllmpl 1m~51Qr'.~'lis IlOrnili2Lt {Fig" 2C,. sixd~ coll!lllma,. IIOp)..

:s1,'jQ<W th .. t d~~ cause QiW ~4e;)~n'Cegf ~~!tj/l! exp~ sioais Ille ~trk:led. kl!l)i!llizatocmof the B~inll~ inpu:n, whichisdJu:e CI11i:ro~yto blimpd aut~ ~:$iOl.'ll, asportmycdlin. ~~.(! ne[work SU1hci[~i!Jitof Fig. ~.R 11~~!Fi:g, IU SiliiX;a~lI!.it ~bi~~I~ i~dirtcdy al.!lth~'i~catcd at ~W!ecJ.·'l-reguila~Q!)' WWI.\l (l, 6., 1) !lind! in t!lis WQf)k. Us desig_n o!.tbi!fiS its ~1!!!l£~ tien, .~l OOI'J.:!>~stsoff t'WO 'p'ru1i8lUy overlapping fet"dbaek loops,.!xi'l1I. of 'w~~iehBr,esu,bjoo~.~o

ali'! 3Ul'O'rejlrei'SS.iOi~ :f:lInctiollil.. Oinc' dilroelly

O!i1L': .ir!.(ji'Ifi\;,'(;lly.

rule!

On~ ~oo~~i~ ¥~g,n,al."n'!~diawd~ Rece~liof! (If WI~18 ~i~<l!~d in recipiC:!r~ ~ll5

on

,tA] Qe.!ilomfIr:: lO!:U;!;. R~d Il!!!ci!'!l!S..@»(Ins; belilt .a;rrt!Vii,

~t1r~ of tr.dinl!lcrip1J1iorn;

'ooiilflg :seq,ll6ITloe patrne'5

I!!!f·tl~ifl;pedes: L;vtemi'i:lMS :

l~illM h~nJe ,b~e5.

non-

di!l1pl~yil1;1J high ~om!E!r~ lIati.Ci:Jil b.~!I! ~a

me'

B II"E1Il"Bli!!!P" I :I ., " ,.."., , " ... ..

~IObp

"."

"

"

".,-- ..,..~

"

mI1qn:Ws and SitJfongy-' ~~Irelitrows purp.rJ1!1lr~ IOl1livthe· e:rons afilhle l8'arlV"explessm 'Win¥"lb) ls.~OOrllil. ~rll~liiorWJ1l (5). '.' &pr;~(nl! ,cmstJuW. ~'ExoIBUDllp'" 'wmrbha.e~

II"muu~xoWJmp..11

jhf.
TGP

~ree

colilSel"!ll1edregioo~ and '00 d~~

~liIiM ali! sliiIfficif!lIItw l~ l~rnduce loorrebi: blimp:1

I~~(llil

C
ExOrB~imp

.blimpl dl[p4Ainh n:JUllinilll pat•. ~m (!If ~:I;pffl.55ioo. l'Ui -·the: ~'IftI:tt&tl8til~~ Wl!iDllld, twQ Blifm:p, tnget ~ites.

@':I:,ri8-s:s,ienl cJ·f

~oo

imdkattedl a ~e mu~t·ed.,
dema~llJ:lllhe aUlmrep:e,. !I)vembppmg) T(F ~ ;and 3!1!iJ1d possi)te BtimiP sitt@
~ijQn fl!lrlctMm;thE! l~mi'!l~

mut~oBlimp

re,arilli!;l E:wBlimp{lop row~, or IDil-ult~o~Blimp (lbotJlrlm ILV;. tJtf!r.a~ Wfflfilj 'VII.• vege1kl1 vk!w; Vl!.V: roli~i1.liIe l~gr~r.!li~·Vf.lg~t:!.l ~t!l!bt~ inoofpo!)f,@l;)n ,gf' i!lj~~ oo~rnYiw,!is· m~~<:!k~ vi~. Selli 'ilIn:hfuis (18); ~i1er,e<fo~ei1Im.all d!lls~liIliliiii! d!1i.ter ofithe: ringl are imiWim~y •. ~itail'liedil'l It'J'utExoBl.irrnp ,e.mrYOJL. h11Exo~Bi~l1IIpemorymi, '~pti'miO:1II 0.1 bllfnpl
e,lI:h

~igh~~om8-r of

l~rOOllIiIalm 1:IiJIe. ~lilillp·KF d~r ~mai1rl ~ii1'latt 1[(1 1[~p~.ssIi:QfI ,o,fge,UI~ ,and @!I!mm iii! dkatd

row).

PiiiliU~1 fifl

e~bl}Os

ilill!!lPt[i)~~

mRNA 'fr,~mth~ OOIilS~d: 'is SliIiWlrimflllSOOI 00 the e!ild~g;~fI:~ljJiS~~ ~'~'!l (If ~ bNmpl ,expJess'blTl,WllitS ...[i.AP' ,de'III(1~, 0 Me (ontairiing iii!!: mlt8 Igene thid C:i(lfr!a~lII!>iI (iff' reportEllr ~5il1(jJue~meinrilLa~.e e\!:OO 1oflhre gEllIiJe,. procllmoo hy nf ~f! vitrg liIie(Qmbi!i!mio~ ttU ~Ump--oGl~fi d~!i!~~ !1!. WIi'!s,b"ud :Slf~i~1!rW muitJ&oBtim~ 1[!OOm[pa:re with (811, e)jJ~pt that the blimp! dlN'A ~as beeiil F'~pla~e:d by a 'l.'iiFtPs;equeliull.

REPORTS
seccnd !oopoon!5kj~"i: (If th~ rgqW~~'l1t~~ fQr B~i~~)plasa driver 'of writE 'expre~Q~ ,!!lm~ the
~uoi~roc.:1l:~ ;req~irei1l1ei1t ·ilJf ~~lelJl~nrrCF:b

'~~hm.uy

!~~~~

~le'\Iie~ w!~e
wn~ripliQ;l'! !i!re

it .1l.C!.Sk:I
IQQ1!!~d

!lI.1J~!I5: daan
twical

Q\!oWl

W!~CI~ ~~~

blimp} c:tp:ression. The AND p;roocssor of the /j,limp! g~le simi.~~l'rlyHnks it,ilu'Oih,efirs:1 loop by il'<i;oIb1i~oryttl!u,t~I]'fJ~'i~ fil::!:[ (he P-c:M(:lfUin} TeF inpl,l.t, but (he O:lher parht¢rh~isa]c OllJ: ~cliviUrn';rnfoolllicis-:regul,atory ~~!'llS d:id !lot ilfldude ANDg<!:I~ depend.e~~l 'O!1! (he Il~a:~eninITCF inpul. li1lI!c guooiroI!lil: would !lOt wrn'k. TIiI1'lsl.Ibcirouit has oon:dlil~ion:1ilopC:r.1lt~m,{l, femmes; litat is, lms ooh1iv~Oi"d£:pei~d'l ,all the 1~,_·i~uiiari!np1!.l~ ~~~. ll1e TCF inp~t tan it fun!cli,Ci:!l ,~it~l~ W!eg~til!'ely or Ip,~it~V'.e~y,~e;.. c'1ll!!se (c:l!o~'1 in ceU:sl!J."C'e~vh)gWn~8 :S~&!1Ia[)' it ~,in& dUl tmllscril~l:i()md rep'reswf GrOl'.lcho (f1), 1"hi~ kce,ps [be whole su.bainr~mi~tll~.ctin q I~~~e c.modicrm. It'S second (!cmd.iti(Di,~al. "'oi'" fUl~elnj}l~ is Ih~ 311~o~~ro$IoiD. ofll!e l;iiJ1'ip,j :9~l1c~\miJtill room ~i:,~'Ie:-CO~ ,~m d'e~l. !IJ!'1 a ceflai:1! acc!.!i!lu!!:tattOrl of blil}'pi ndtNA {atIlcl

be as miU1Y as -~,:500nlOlecui~es ~ii nmiliew, g;i\ll~ sea. ur:cbin Il'I'::1I.ru>ilatLOIl m1es: {J 4)1 [m.<Dfiil
sllllT1Ciantro., It.MgCt: ooc.u.pan.cy

.by tile
itl

Ita;ns~rriil'lliolflfi!i{:~r (.U~ :pru1ncular~y

mclOf) (n;. S2Cl 1Il~e' !rn.ooirel.litacts '~oprodltOe tile ~.lliO\'iim.g ItOfU!! of leiil~ C~lPressiGilli. a'O SIlli'UaIUIlIUOOil~ Fig. 3. Mea!fl!lro:J1l:'J:lml8 ofdm Irn'Moopt cOOIrenlratioll,s ilrldJtcat(il Iil~H dmiil!l\ ihis ~,b;lS~ b!.i1.lIpJ get](l: 1llilG:
is P~~~'lg;a,~l 50 !fa!L~wi~p'er c~n·!]glUr (~is is ()!~]Y!:lrewpefiCeHlof 'I:~ae ~~iml!.!m

U1e;SJii;'i[~-mi~lliaC~ :nlid~;] •.'1IJ]Jie Hn1pl lfaclQr B Ute1~diRa.p~rWt!l d~e cells oBJ~ 1!Li}~/8' gene ,e;.,;;pressi.yil] ~1!!f!iSolT as, liI~ereinforti!'1ig fecdhlKik: loop i~ Ibro];cul. Thehllll:f';':lif~ (If bltmp.l 1!m.11· scr,i~t~isaOOtll~. .Shoot'S in ItlI~cmiCmi11e~ and narwL'CaUy d:til!:n~i i~:g~M lal{)f'Y S'l1l.ms, Her,c, W(l 2.5 h(il.lffi'S~lIil tbe rn.1G.lOOl{icin'ii,. vcrsus a. derau.~~ re..;;ol.wd Ill. .~mliL':regUil.ator.y ~(]~WI'):Di:9lLlooirouil tlw ,eol'l'lllb,i!l~ th~s('l ;l~~(:ls:un (tilfli; !l:1~~ .a:p-. ,..v~~~ o:f 3 II) :5ilO"lfits fijI" ~11 pO~~rn'laJ ~ urol~~ e~'1~!wR.NM Us)' Mea:t~\Jif:nde, h{!i!l>~t- P<l.!'ai!lI!S.Tile S'II!,ki!'cuilf~ ki:!1·~~l~ dq:_!e!l.d Oli'! '!W!M'. Ilke WillS lipAKi has difl'UBed to Ole !1.eX!! the s.)TIlhes~s "!1dll!f;~vc!'rates:or i!le re!ev~t Iier (jifCN~ns,dte :1i:Jtlllfe e..<:OOlenn (middle tier in It:ilRNAli~nd[iilRlidll.ll. ~ wdl asen Uu; IIt~ m Fi~. 3). TIle ilnteR':Ci~lJl.arrr'd:i:t]\ISi.(m mIe ofWnt.8 fini'~.,esor 'I.h,e trnlllscr,i.plirnl r&ri.clors,fu.;j~~~etlicis. p]m ~he ;i"l(Ilcclili~CSIj) \vhicbil isbeued il'l:mo.g~ re:guI31(l1)' lrug(\l~ s:ilcs (13]1. What d~c3:pp~mll.llS 'Imlik!ll~Y h~ mtil~Umil'ing,given rttimwl) Siln;aU IrQ do~. however. d~M(h" on '!:h@ get~ft'!:[e eisinWm-oothl!liIr di~J~;l!Uidi dl!em~~ lI'iat ~a",~ res.yl~u.11n')'~q!.!!.¢Iil~~or UU~ bli,upi <1.!:id'i."'~iIl8 Tooooa'it~~~;eCl'fO$thi.I:p:~ by o!h~ (i 6), ~en~. w~lerei:l~Y!aiq~e r~m~, h~~edb:!l!ck liIpoIl ~oe\plCJif ~~e WnU;;~~md, thl;l;.101.!bc:iw,clJ!t~ loop8, AND garue!!, ~r!,dI :!i!IJiIDfi'-'iP!IeSS;io!'! famelior! is 'l:bcrebyfl(ltiva1:cdi w~thhTh the llilesOOem18i.~ are encoo:cldL
ru

5cri'ptiO!~g.~~ O(~, it s!~S oR: .~U.!.~p'l.~. :~ID' OOgl1~~lpoo~ei!il, CQlI!ld ~ sile[lci!1£ i~ Q'WO :too~ by ;uernJi~lmlHI: olf [acki:U!> sHd~ .ru; hislo:lle 1'Iadh.~ ytnram;;fc·r:'Jl$efl (17], The :slJbs.t'qIIJ.l!en~ disa~ pcarrrulca of iJ1JOO~£:a.rJl-Cl'IiOOil~1iII from ~~lc cells \vidll'l'I IC:Ei~ OOO!i.S C!O'uldaloo lres~]~ iti Gr\ol!llCl'iO f~p,,~5i'O:Il I( 7). The ge!w~licreg,l!!,~atory code is .<lJ. ",~tic Hfl!e<!fs!rtoc:tu;~, wheoeas ,e~~btyonic developIfK11I~ jsi'nU:tl]~:!>ically .1IiproCC.'1;:S dri.ven by dy-

leiiritoxy •. an,d the. SiliItlC cYC~C}oli' cvcms

I:'UWlSins
EO. IcI.IDiI\lic!Som, llle lIif:!!11~l.wy&>;fil(l:!')'1.e1 Qe'~ R~~lai,""'Y Nmt'.Wk.HII Dew•. ~'1 !l:!Td fLll1fudOl':J ~'AI::~[feo!l'liC P~t 5:.a1l Dillgo.. til" 21](6). 2. Eo. E!(,. O:l,Yl·m~ ~t iiJ., 5tif!MeOi!·1!5 .• :l'6.69 (~OO2.l! :!.S;, Ili:rai! .• t iii. 1[la!li~!IIIm., Pmc,. Ndr1.lI!'mI: 5<l_ 11_5A!

~rn;s!b~e lmns~l'lion

!!1.'I!te

:(/3)]. BH~lpl IUclof'

ooursein, !.his tier of cells, wl1ml: it opGlllttcs widl very ~.fIlli.Iai"kiil;r:t"L'CS {fig. 1 ~~g. S2C),. Sl!ll!c~ro1!il r:eacli\fatio!~ .~Ii'!.tire ·ccl~ Oil t!~ m:s~od~ of !IDle I!:O~ of :grenc iex~:srQ!] (!by ]~~".m:I s.gnkl!l:i!~g)is lrot o!>senroo: Once &limp 1 troul"

:1.

Referenc.Es ,<l!~dN~t:es

j]j.o~ ~9.!j;ol (200ig.

~. 'T'. i!Mlltj]/klM\:l(.~. lit Wlkrllt11~naylI'I:@.. E, ttl o.wtl1,~m. ,D'!:w~ BirIL ,21118,~S' ~2(10!l]', 5 .. 'C, S, mj, E. H. IOnfdls,ol1l. ,~II'. DiaL :i!~3, sn
(21006). 6. C'P~ eii' iii" D~: :B'iQi. :3!1~,U~ Q006~. 7, C. '(. I.I!g<lfll,~- It .Mii~r, .M_ Ferbil'lia, !D- !il. .m~~~. 1Dwe.l~mtf:lr Hili, .145 t1.99~). 9•. ;!L,.IiI. 'Wltr.!!ffliai'i!l!y.'ilk);! ~t D/,. Gi:'M.l'Ji ~IJ, liil'4

J. c,

(:2:f)O.aL
9, S;,~, .DlJ,~, At P'III1:.t!tl~). t ~lll'ist1al1l, L Il, ~\(:6rew. [;;" ~C;!m, .!il~, (fll. :8i'e!l.. 15, 2625 t199~1 T. 101,(;. ~. Chw~!l!ll"A. Iii. Wi~r~I1I~I'I;1iy~~, (, A.M<!IJ! X. ~V.• t'.);~i!TI, .o~!i.YM.e!',.:!,'9, ;J;3'1 (t9~6l. ,

:n .. 5:i!e,5~pporlif!!]IITila[.e;rii'!l ,Ilml 5tirocil? G.MinJ!'. :li2. m .. (, li:arnge, ,. Iii. ~liIll11rl, [t R hkCi.ay, D.& 8ftJi: 27'\l1'
2Q W)O!ll,

w.~.

H.

1'1. B!OI(mri., E. H. Oa-..td!lli11I,. iPmE hI1.~, Acmf 5(i, U..~iII ~OO, 9"~;I'll (~OO,~. Ji,'l. E, 1:1, Ool,vi.mlOm. G.l'iN~· AcrMtF f.!l &'rJi)r ,Di£~'~ml:Tl~'

~liIlli1l.1 Simps ~iIm!9f tier orlly) h111~aI StMe: Gr~ll,Id1Ci>" Tet n;tpllif;,~ zil9'J~Ci I:!limpi and wnrs '@(pr,~sl(m

IliIi~ial RiPS (mtd!Illil'

3fl1!:i

()urelli~lfS) ,4 Wn.t'.8 sigiiiBIllilQ: ,amOi1Q

sig'!:aJ4)el'leraUrng oeills i~~~~ 1I!~~.tOO[I'!; llgallld dlfl~$~S tIl rJt;llglillJorl~il ~li!!r ~to ':;;!)l'IP ., ilil I1IDi1ti!!l~ 5 elill!lp~

1n.1~S!III.nput ma'~erml
Ol!I'li(OQI~py :st~bIl121K 1iI:i).ea!t9l'1lli1lal 'vsgatal , pale

middle lie-.r to, 'OUlte~tier 21 Ilfi·cm:eflln +- Clti: dn .. n

,b!imp'f€il!pres5iI!CI ;3; ruJ.c.ffieIlin .. 8ililIlpll

1 V!lirntBlig3n1il1 ,If:Iilliuses (rem, liMer tie;[' to rmi[j'dle tier I!Jr

repl'Elsses

~II

~!!tmi~ 'r~5, (!I~!iilrldb, R,l9'S:ij, c V, C~llr'~ra.. ], J. l'~,~. IEIIi:5lKl,lt 1. Snit!!!)' [, Iii. Oiwi~jg~,}. I'(l~ ~fqI:, 114.65 f19a4l. :l!,g,S;. S'r~~s, Ri!ir1~\r, ]1.TlII~m,~,t T.>elll~kle', S(rt~~ ~~.i1I" UA,;r (:!1DIlIS};pu!JL'~rn~d,~m~1i!!.~ NfI!W!mrng .2:!OO6 (liO..l12~f!l!.il!!fi~.I!!!.l!J.~OOili!~. ][ 7. I, Gjory. ~ 'Viu.t'i. ~~r. I[ Sl.'ill.1 ~ .. L~~iil~llt Mert. lrllmulilr.ll'. 5, .299" r.2Ibt04). '],13\ [l. l.. ILivOlIl!t,lit R. Hi!i<tJ1Illft'Eli~lllt J. U, ti.l.ooirtl, R,~. 8n-'iIll~. [ H. O<li!ililw!l, De~r~mJ:l'J't l:U, ~U~l), ~9'. S;!!,~f;IQrl~cl ~ <! r:~~!j~~~!ii!: II!1$t~~, cl ~~!!ef~tM:' ,Mei!litiFU~ rl1l!~llip W5J Olnd tI,i INI~ ,g,<'!rn1: U.

w.

~oo.

i\lm:leiBJ Irn~CB/lel'iilm 'Ii m.aternl'lll Blimp ilrIitia,re'

cr~

wnfB expl'~51QIl 1(~OM<ep 41)

H[fo.,.li7ms.

~rRfSexpre$$ioF!; !liJll.cEU.eilil!li .. 'Oti); d~i!jfEI zygoillc blfmp~ (10 step 4)'

SlIp'pD,rtingJ Ol'lll~i Ill!! .M8It!Jl!riill '_,.!4!iIIO!~rna91.~f!!:it@ornill!lnLltuWj191~M,lrr\iMlICl Ml!tl'fl.al~

ilrld

,M!ltllOd~:

iF'~g.3 •. SliImmfy of' IliTnf,chanmsm 'by wWtic'n the dyu'lCllm:k, cOilflc~lIitilfkal~ly f);~ilInding~Qru:li l(Jf wntS <lIB£! bHmp:'1 e:.:.pressiOlllli50 'gelliJell'illted.TIile dl[olwing £IiIGWllII :5,f;l'V!£1Ii1.tJh,.de!,n!lage emlbnyo V11ewed limm ~b'e 'l,i'ege:til!~. pol!ein iHl!I!stl'ateitll'e radial~ ,colllc.lemulk org~lliIi.2lat.ijionl., IHowe:v~!r, ~'IiI:e:events. i'n:dkatedin ~"tii:e! mlmbl!lftHi key ibegili! art f,C)ILU1ii1 (I~ea!(ag;e(fllid Imi!lfiai O'i.lt to' m'!!Sf,ndllYIlli1i!' blili'_I,i!i stag.! '('IS 00 2.1I, hOIl r';JI.

figs. S;1 l'!l ~~

ralll~:i'1, ~~~r,e:IT!QIl~, lSo TJJ lie .2:00 7, .am:ptOO l Oct.ober .2007

1

1'0.1I.12~ck!il~!!.:n~,t.~2~

REPORTS

Telomeric Repeat-Conlaiiniing R,NA 8IndR:NAS,ulrveillanc:'B: Faclors at IMlalmlmalliii,an C,ihlr,olm'o'somll Ends

l[:lau'iM. A:ual~in,t2.3 Pa.tr:j,~k.Ill!ekbelilba;~IiI,a.M ILeia KhorialJll!i. ~ Ill:le~!!'I GllllLU!tt~~1l ]i[ll!!chim .~i~.glne:!,l.~.li",
i@!I~flfl!!f@'S.1~@

!'~pt.':<i~!,; ~Q ~~~~ 3'

~~d~

telQ:_~~emj!e ~K:ll~1!';y~le Q~;mlpri9}S a reverse I.m:nscripmse calnl~itlc sublilnil, the ~lcm~1me

Qr ~'I,l!ffi;nKISI!)~HlS. 'Whe:

RN A moiety. !I!1l1cli !.>cvcm~ aCCll:$SOliY]llIlIlors l2., 3',. 8). l'h~ SaC£hatwJ.~lrcf!S Ct3Jle:Im-;ftME.'>'I,~, p:mt~ill bjil!d.~ di~lty ki thL'i 1~IDlIWm~~ R.NA

a.ud ~o the siil.s~e-sl!,o'il1~d~~d (c~a"'i~rie DNA Iii!!'idi~,g 'poolcit!l Cdcl.3p" which feC'!ii!l!.!!5 l[Cilo!~e!'a5¢ w' dtmroosml1C: !endS h~ Sph~e {9-J/}. Tll!n:ee: :E.jjt"IP;~ikcp:rolCil1!!i (ESiI"I A. EST!.]3:, and .EST ~.C) Ill!iv"-'i booi~idtm.tif:iooin.lhl1iifI:WlnS; (12', f 3) .. EST ~A m~d EST ~B int.eraN. '1vi~~'1.G:lol:l'il0r.ao;e., aiid owr" ~)(p~~ipl!l. ~f ESTtA 1$;!d'8 00 Ih~~~'I'fl~~(u.~n.." <l!lid 1e~(I!f!\iSre if~Q!'Imil'!g(12.13). .ESl'iA,. BSIIB, ~ <l!lid EST'I C 11:Ol\rea.1so been idcf!~:nedJ ru;·iu.!!II'!am o:ri!lcl~~ ·of the CfJel!W/Ulb(1ili£ ,eleg.t!.rlS SMG p.roteins SMOG, SMG5. .aM. 8.MG1, respoo ... li''I,I!~~yJ3-.J6),!A'ilili(}'h. are c:iJOOi:-ors: fO:1i !11QJ"t'>CU.o;.c.>. (
I1iI.OO:ll.loo. l:I'iiR.NA dcea;y (NMD) NMD ·ool'l;l!]liidii!li)F}'~pri~ (/4). 1rhi.'l ~lltilnrul fou!'·~tlierSMa

I!].NIA-prc!t@~n OJ(llllplr~M!S locart@d atma

@li'Idl ~f ~llil,@ar @l!kall¥ob(~llHcmciSom@~.

h~@ b@@r1 wlIi,si(f!!fed to b!! ~marnurip'tiimllii!ny :!I:]~.ent.We! demo.nstraite! tlmat 1ni1i1mmi!ll~jantelollill1l~e5 [lIre tr.[[IiI~lITilllled inro~LoIliTleri~ Irrepeal:-.c:c:mlalTlirtg RNA (1rElftR:A).1rEIil:RA f1!IolE,©ules ,ue he;te:rog~IiI€®rn[1iI lemgiU\ alre tm<linl:\luib8'C 'fiITomi seJ;I'I:!'r.13I1 sl!I'brte~ollillli!ric lodi iI:owarc:llChmm:o~®l1iu:! el1ldls, imllile:!Itocat~H: te,telomerre5.WIIl!' alsn Sh~liIIthgt .S'~PPHl$$-(lfS with liirw'~~hog~UI~( d'ef~ds! ill 'Q,~liliiti'l~.i~ (S,MG)' ~i1(lOOii1I:;,!rI!hikl~ ;g;~e !~ff~(OOr;s cd ~~:l'!:Sioos:e"moo~md m~S<Si~ngilili'RMIA d~cay. a!t~ @!i1.rich@diat ileW~er,~.in viVI:J.. Ilf!'ilgatTIivtW rtQl!!lOO.!· i1E..RRA ~Slroda-it.iQ!ilIWiliIJli!oo r·emallin.antip:IT01!oct(·hnlu..!.!(I!Som@.md~ff1Om 1i@IoIliU![i@ lo:S-:5. Uu$,. telolTl@resar@ ,actJj;v!!!~ytrnfis(lnbe(iirilOO TERRA., 'lln~ SMG fa'COOr;~ lfeprE!SI!!f1t a: lrililaruecular I.in'k betweenl 1rEIRM. regulation and the m<l;inli:elil'ilrn lie Oi~1!elomfrce~inl!eglnity ...
Sj~TTAGGO"3j re,peats,wiO~ Ote {j~ch slr.:md ,DXlEildli,llgbeYOil1d1its oomplb3l1wHI. to6nm sn -l112lo:!rui,:IiJl1cli On.cy 'oqlt~p· ooi1iTnll.l Imman ovcrh:llflg; (1, 3).. Tha dOOlbJ.C"llllrnndlli1 part of l'iC)~Ii3I!eil~Uswilh :a: C(!~11i!l1.3:l' clack Inilal d!~JCr~ mIOJ:rt~ is 1Do1llil.dto a Il'WIltipJ:':OIL'itll.ca[illpllro!. ~l~n~~ 'Mwir~Hca~ivelif~pm (l~j)l. M1I"m~~~ kll~!'a a~; ~hclrorln, \vh~ch p:ro:v~~ '!eto~.~\l ffOlnooiHgfOOog!~~~ and. ·prores...ooi 0lS ~~aI!!ll~IOlT!;~caan~ri~e!ll!F!clcm 1iff<I)'l'> of dUp~en S!.!:atr!d1cd.breOlkoi {<Ill. ne liIele!iOOhr(mH!I~ic !lIme of l!iclolW.cres, d:ldJigcnc~css n@iIMC, and tJ~c.~ l'SWiss 1:m5mlJt~ for 1i)i'pilrim'fClb<ll (;an~r R.e.iea:J~m (15R£Q, IIQ silence l:m'31iL<;miptnJ)i~ of C:)Ip('lrill}GI'IHI~' 01!·1.o66 ~PIiII~n~e~. Siwi~lllilillldl, 5'~hooltI!1 !if~ SO~~,"~.~., ability ~ iE,~1e I1ll'l1.!:ch ilIi",,~ F~d~!,OiI~ 'Ce ~!lii5~FIiiil~ (ElPF!.:)"CiHlIy in.~cf.too sl!.lbtc~oJll1crIc.ffiI]ilOFlCrgmm:s. which :llllS l.aUS<iUii'ii!·.,. ·5iM!Ii!~~l!d,. "1r·O:iiliiei1 II! Ge~etfcs~ I:;; kl1(]!\'or1il&<; the OO:iOliliJ~r.e posr~ilOti'L':ff'ec~(TPE) ] ~~~\o;mal ('entr,e~o,r (imIlJetenr;e illl Re.!leardl (NCcm. C~{5-7'}I. ~ypp'OOlIoo Ihcidca M!loU.' 'l!ell:;Jn1Cfe~ ~ UU 'G~nil!",aj $.wit~~~L,m!i, ~UI~iW!'~i~ o.f lPacll'laj.Oepilri.

a'!1~ @~>s''@ontiiaJl (hromo.~om!! ~1i'J~mty. Ul1ltill lliaw.t:eWmlle!'i~ fo(r

.· T

poi~~Mptides:UPF]

(SMGi2)1 UPF2 (SMO],).

1nm1il~pfi.oll'"

lIPf3 {SMC~). and. &MOl (U).

eiol:il.cresmHIH e...'<SCHli~lfiln.clion,s; for ~J~lfl~800n~ £l9hmly d.ur~ilgmLtosis._md,

To tcs~ WI:H}d~e:.i le~:OOl';2resMe'

aU.}" sLk"m, we pcrfolll'lOOI NOJi1jbrnml. blot :!I:i'I:lllysis

oooole-

.of RNA fronD, It hUilllll~ CCllrv~ca.1. iIlC'll't ·OCtlliilCl M (Yeta) lil-u,:ing !;trnndi.-:spG:Cilic ,vdome·ric p.robes. n1i$ ~p,~mach.o~oo dte~N:~lC~ {If TERRA. r rn!ij~i!!:gin ~.ZI.': hm """U)O,'OOS~U!)!lQ ~l 1.e<J;,~ '9 kilo'b~ '(Fig. l,. A and .IlJ. nc; TERRA sig,~al was .aoo.~is:iloo.up(n ri'bomu.d~ ,(RNase,) ~~ Ineml, ,ooi'1lfmnilllgi.hllti1 origtmliloo. from. RNA
(Fig.M) 'TERRA molociJles am fl¥~nd ,(D;d!Jj.rr:ae;~iOjfJlian(W oor~tlhl UUA:C'iGG r:ei.~S, We oll:lly derec~oo Ol.f1)i!~t ~i~rM'!!l f{i!rdle oo!wp~emerHa.fY CCUAA rep;!:* (Fig. I~ C A).

8ivl@ly iml

IIl;d(:l}r

m~rI~.o:~G!I!!l!Irrtio;~nrlMil:robiology, :l:n:o~)P~'\!i.;J, I!:al~. "'To

tVh!:HiII (ol'I"il~palTl~l1~il'

iooldilirn.lilngJ!ii!r@i.mc.rn .

shol!lld be acdflijiie{i. ["m~il:

Ir.mscripl.:io~_jly s]lent r!l1lh1lm~0l:1.<.l.1 oe~lls, fel'oHICrnse IUOI!ootes: telamere ~.ciQgm\l.hJ)mooiSl~is;by add:LngIBl!om~ric

S:liISg,eS(ill.~g

tlmJO:CUAA~m~l..lli[lfutlg RNA loolerulJe5 m1gl.t~. ;:.:.t'>"lOllJl!Y at very lowlevels, e

IF;g. 1\. ~d~li!l:iilildati(mof HRM. (A) NortheUilI b!I(lit i1Ili1l1i'~$t (If H~La cyt~las!iilIIic (d MId liI\J1d~r (!iI') RMIA with mll!ild,~dfk t~I.ornleri[ . ,8il'lid 285 rib®5Ctrirml RNA ~rIRNI:A) probe~.· BI.uJk
QJrrCIWhea.d~ ~oiliit 'In IlIIi1de.'ar l~rOOl.lr~(i!r$ o·f :2!BS, IrR:NA (fractiotl'l" a1ilolii [HnO~~ .antithewhitE arrowmelAd :point5,w the :I!lliidtl!lr@ :2 as I'i'RNA. (8) No:6em iiJlnt arnllly5'i'sef 1iI1J(1~,r RiMA '1I'IIiI:!1iI al Ill'N!A PJob~ ~lI(!mlhe XpffpSllbt@~(!!Iilllelre'. EtIidffiuli!l bmlil1id~' 1(8t!Bd' $1!tJiil1in:~ rn' ~he gel is )IiLMI1J as ~ldd:illig ·oontJ',ol'~(,.) HeLai lliludei!llrr RNl W;]/'i relilerse trrilm.:ruiii~d (1RJ1 with oTe!~orWfr"tih. 01,1'1. (~ootro'l Rr rMctil)filswere !lPedlOiiillBd by omiUii1.glhe lin :'i!tf!p er Iby pm(lfmi!ilg~!! IR"I" w'l~ il!!iI*'ef!SJe: 'OtigO~~i~otid!l'S (g:r~Ia.s <lInd 1li1W. P{R. was perro.r,rililedl with ~liIe i1dital:m p1lrililer P'1i~ Qli"id '~mplat~ ([1I!IP). gi'l" ~il'lornfc DNA Pt:R li'~diJlm ~~ vi~alUed Iby Emir s1i'lalting (bruadllirrcmuads: rn l!!PPEr l~fHels) or bJ 11iI~linridiltifilil to dlll ,atiglHllU!l~EliIlti:Ie ~Iline ,(®~, rero~rriliny o1!l 5pedlk~'btelomeri(~e!gia:1iI distal t!O .an 9.tlwe;f pi3lfle'lisl

.~om @~~fjm .....

mI:P, .• RN!

......,~om""'''_Df~nR:...
IAN6

,II;

,~,,,,;

.;*"4ti

......

~ .•; ...
in

,01 .Hift.

0'1'1. 0'1

'* an

't

~ii!l'

O··1nIl.. oil

REPORTS
Tl!:RM m'Ol~!!!~,~~re ,dl;OOo~~d!!] d~fF~oo:~t of d~n;~!:\~-~~r;M;oo>Ql !]i!.!d~~ W'i~~~ :fl:l!!o:~~n~· .p!. ~tmlm Imd!'i\'XJml'l'e~1 1~~1es :~~/\')', i~d)!c@~o,g Iy~l~d! (fl,g. iiC:CcrM~w!1ltUni!1l.£ .poo~ OQllsm'.a1iOlll of'IER:RAin nlllirnl't1!als, feV\eaJe~ an RN~SiC!llsili.vep'lJl1l:ltltefilil1lil,eill" Hyhrid.iza:niotl oJ mllilt:,k4'1C' .RNA. !)liOls wiru1ll. iii snainl1llg: ";3(}%. o~·.Hela and primary human Itmg flbm'i:iLa£ts (fII1Fs)dli.'>P~aJ'Cd!.3 to 7T.ERRAfo.cl. ~Ir:obc dl.mvccl fro"ldn~ ~lbtdQm~ric oogion of \...~~~. 80 1\'1 1I]W/~,af l~[iju~. oSI!OOsarnOlii'ia ~Wt'iitl1 ,ehiXIii~o.ool'i'M':; XplYp ~i'I~rl~dl1J TERRAiuk~ I¥ybridi?~~o''ilI~U~I'I~{F'~{} ~.W), TIfL¢~f(t¢, cells: ~nd :iti!.i!rla!ioe r~<1!~ 'C!lli~~U' (lL!iUs d45P.!a_Y$d. lfim~ 5\!i.b1_eIO!'!)~~;tre~IJs.oi, !ta,~rioot\attn!l 20 hl 410 foci (f1ig,.2A and fig. S], If:! and C" CO!~~.sler!t\",.]lIi.dle Nortl'!en~ blots, our RNATERRA IttI!1!scriptionrnlghl' ~lso ~rt· at su'bteio:Iiueric leel alld pr:oct.m illto lillie ll.'l~.m:tlcric. IlmC:I. 1f,~SH anal'~s fDi~.edi (.Q,d:etool~ OOCUMr.cpcalTo. Ilest Ihisl:l)l'paOl.csis', we reverse ll'3iiismi!bOO: COi~.Uli.l~ingRl'\IA Il'Iolccui~~ We dlCil~ IPGrfoon.>L':d. RNA-'fJSH o"ii!lcrilndiirect.iit1ii1tIi1lXlimoornsceiiioe, Ili'Iu.cItll'ir' RNA. u,"i~.~ill.€:tomcric 5'·(OCCTAA),:;)' (lilu.&OUl~d!)otr-dl~ ((i:r~)Q(ui1pI~Itt:l~m1mry I:Q ll)f,lj In.~llg 1IIUI(iJbOOil~ ~~i!1L'lt ItiI~~I~Uli'lall sh~lrorijr.! C'O!llpcl!tf.':In Il!R<:1p~ (1f). TERRA fod c(ll~~· ~llI!t!ti:ve UUAGGG re~:i: ill TEIlRA!limi ~o.lY!~lem.<;iC:,c'llrnl~~lio~l I(PC~)""ul~)li~o; 1I11e iz.ed wj1lh~ll fod (Fig. 2B <lndfig. :S~D)', in· dmve<!cDNA l!ISins,pri:II~r ~<l!irs'~ocar!eCII~!l the dlc~lin£ that TERRA, is <1 C'OIl11i'OilCl~t ,oofhm man ICloa:uK:ri~lu.'lll::roo1~flullmif].We also dlctootcd sl1bwlooue.ric regions of ChIi\1JIMoon~!CS pfYp, X ~. 'p, I] q, 2Il:l'd. 2p (O'~. and 0.2) {rig. I.e) (17), J TERRA. mo1oolil1cs a1. 'dl£:elm Qfm'l~Il¥,hascQ]lm. The: PCR ",:rod!oots llilla!wh{)di tit€: :prndll!le~s n'lOsoa:r~(l8 flliUlli'I. rnnr,L1I'Ila1i)' ~~ mlmlb~nJbro,blasnl! sro!1~Qn~ffL}JuPCR ~n,Hf1~lign~ (lr~~lfI(]!1~~{: (M.~:O (Fig. JC). Th~ u~,~i;ou:rol'!of TERRA , DNA (Fig, I.e). l1hm" TERRA !'l~IOOll!ies· .~ wi~~tl'aMCripti'O!dl)! s~le!n Jlle!a!lla<;!e d~mo· I!n~ribed from di·ffe!<."-!1tlelomefC8 OUWaL.!ie ~lllfS 'i~c1icO!les ~~,!l I,~( ~l~e: TIERlitAre· ill
!1tOre, Ute aJ!P!lQxin~~~I~lf~~ife fQr T!~:[tR..A,ef J 11Q!.!lT5 ,'\,~!!"~ <!Y£!l:le!lt\;ldi i~l cells d:~le!ed f'Or 'UPf I or EST~IA (fig., S5).. These l:'eSulcsSl:J~l liiIs.t SMG I?ro:treillll p.roJ1lOre du~dJa~,loocme..,.i~of TERRA. fml:nl tdO!l1lCnC ehromati1l'l. amd d1f111)diff!'l~lr~ SMG lpr{)teil.]s i'i'ii!i:gl'it l~ihI)' l!i.on.l'lIjdUilldanl Ji()o~es: i.l~ ~~li.ilp!(l¢~~ SUppofli:!lS ~ di~l 1.''''I!!iA;~ tion for :ElMU p:!'(!lleit!:s in f~gu~~ti~'i:g lEllRJI. T
!lIt chmmo&u1iu: en,dls, ·c'hJic)m~tinrTaCI;imilOl;tioll cxpcn.l1J1ifut) :[dU;olwadi by Wa;ste.ltI~ blot: amml:ysis fGw:aloci that i1I~I.SCVoCit1 S:MGpOO(ei,i]S ,m'('; prosmn ~n. cI:liMililllUm ft.:le:~oos d~ri'vOO. fmJ1n

~idwi'~lIdl[(lnq~s or S.plna.'l¢ !H~LaOOL~ (fiS, S6A). [n additioJi!-, d1!'!tl~l1;alin i!'l~mi!.!!lQ~ret~i[li~t!O" expecl~'r!e!llswiih Hey oenl~'l"u:aa!s denl-omtrnted 1I1.'l!! o1~!:c:ll~~~i!~·ooullil'dMG rro1ei!lS S ru:c se"iImI!=fol(l, clmch'(xl at teJ].o:mem:::sin vivo over A1iu"lI\lfeat S,e.qlmlilC~ (r~ So, B aim. Cl

\,~ d.too. tmns:r~ctEdi .Hc:La.~~n.s withp:w:"

prolein!'l,.whi6h l~ 1(1 !MOn.:: emd~!U de~)~eUo!l tbm dIe lcn1ivi:mI'"'Jl!i'Cdiatcd! dCiPlello:n used aoove (f:ig. S'2l 'Ibm1~nalresmc.t[(:m fragl!:lcn.t (T!IR:f) Im.!",s lC~(m:lc~<;sooiamBi:l alier its .syuthcsis, C1JlnpG800 of sub~d:mmoo.c~cri.vOO.RNA .:31Ild. a1n91~s iml UPfl..:;'lm!.EST~: A.~~pk:tcd cell.sdl[d, UUAG(]G ~l!>. ~Ve amoi'l.'VCi'Se InMSrnibed, Several SM"Gproll'llilS am. hwolvoo.iiil, gC'itPlil:K'l ootrL'1(I\BaJ :nol.iJeeabJ.c. clJ.illlig~ ill mf Imlgrtb.s. lilll.1il'liaJil nue~ClW .RNA. "!.vilth run, o:n!¥llll!1ch::olfilla sra;loillily .Mrl11e:!C!Iil;'i1l'iC ]'I'WillIlmnoo (J2,. 1:1• .19, 2'0) of «(f["RJ COiltalflil~g fUve S'-CCCTf\A·31 Ii'Cp€:lIl$ at To de'lf:oohlLl: glG~JIle:. SMG proruilns Iro.g-1!i~3te N~nh.c1~. a. drel!CaS(lif~ 11OO·~niu!mShy Ule [clgl1rK.>:ric SI1!lW \~.~ S~ cwIDlem Ul.'C 004(l!l~ri.(1 O~e 3' end <lind 20 di.1tim'lc!i\'C: Hl.!cioolij,&.o;; ~ d'le 5' T!E~ i!lt cIU'O!]1Q~l~ e!~d<),~1iI'cil~focoodi .Hda e!]d (G:-n •.), <lfldI.PCR.~mpHnedIlle cONAwir!1l cells wl!hloolh~if!.!!,5ies ~·pres...i!1£l .shGrt IlimilDTh~~!'! ~!g!1<11 ,oln<li!~oo hm d\'!'iOmoootnecndlO:\1'!'WO oo!'1!lti!e oT.L primer WI ~cmlibln;Mtonwi(l~ dl~gonm~ RN~'\s (.shRN/I.S) diro;;hl:!l<lgllll~ UPFI.ESf'l A. I.tizcdi 'Do II'he si~'Il<llderi\l\edfoolflli~le!:S!iLijal tc40:mr.icl'\epeats (Fig,. ~A), Tllms". UPF~ ruld CJcot[.dCSi for ~b:le:].o:mcr:es .of dlll"OlDlOIs<mmcs ] lq SMG]. and UPf2 (fig" S2). ~pl(!tim~ offUPfl, EST~. A d:CI:l~.elionf1ilJ:Lghm~cadto 'dn.c' :suddml. loss ami. XplYp ~o I. ill Fig. ] C) The PCR.p:rrOOToons lESl'lA, or SMI.Glinduooo. :lI,5'lIlhstaJtlia]ill.crem: w~re ,iml£:mgooetrm; illl'l. size 3I1d~tt¥£ I~OSOu;dn,.. il'l 1I1~G:~iUMl'l~r !lfQ~~ls dHspliayung ti!.'::lOlllgnro· of !:lI1.ti:l'c mlom01iC:IrnClSa1 SOll!:'tl ~hromoml!!Jfl ¢flilh,yMdiZiill(i!1'I \-viin~. jlji~l'Ii!lelool:id~ ( {Gel,111I ;fu_~odal~dTERRA :PO(;! ail \:VC:U in rbe 1'l!.l~l1~f ~ ~lfId~" ~rl~«'eI!1l1y.II)Nt\-ifISHalil;J~.y,'il~ C (i!fn~plbase dlro!11{1S{miJe!l:rfo:~"!lUP,I ,·or EST~I A Fi1} ~.el' 'OOIHl>J:Luin:g sequenees l'h<l~ lW¢~ ~~ptOC:~ft'C oflQci~rl);()-5ilive cell ~Pi;Q.3. A<U1di B,. fj~. S3, depleted Hcl.acell!s I!'C'\nea!cd :11. :be-- ~, .se\l'enfbJkl mr &.!~Lelo:nKlri'C ·re,giQrls d~~ to tIle dj~gonlll~ A and! B. ~J!dfig. S4l~ A :~lilde!Ti-'1C~ WI.!!!! ends, A omervcdm!" UPF2..(11eplietoCl oeIls, IlIJ.(EI01!Igh t'hc imllrea."C ill teioln~f.roo ,cll_lUJ!I:lOSO.!11C cl00tilCies U5edll f'O!:lhe PeR. l1~ehele!'O£'mot!S si2e dis:mbllltLcm of idl.C' PCRprodu<:(S is inferred s~:eady,,$If111)e ~£vels of tile ]'<,ND Sl!l.~ BAG I twofoMillCreasc l!lfIassociailed sisl:C:U' miOlillCi'iCS alnd .1IJfi),lI:~ 00 flvcfOldi iJI'C~in. tlJ'Jllnlll:nC fmg. (2 J) wme sin:uilarly Lm:mc3.'>L'idl upon. dcpkt[on of Ino ·be· due to ihe PIIC:SOIroCfnl!II~Y UUA.GGG o Irepe,\'l1S in [h,e j.'rogicn of TERR.A aJlt<!.tO Ill£' aUleS1.Cd. SMf.i faclP:~ (fig, SJ.D).. 11m observoo In.mts ",vcoo alOO ob.'lO"iIOO (Fig,. 4\. B aJildJ C. 31:w:i <i,!lJIIlc~,di!l\S. 6'1fR indii f:fcmrilJieg,is,te~ durr:tn,g .wCU~WII!!~iUijO'$!·of l'1ERRAun ~rudeior :SMn· lig. S.7]. Sil1ililow :iil.c~ilS.!{,\~ o1i)laink-d forSMa~()If dep~erod ,oot~ w~ ~O!: doo to a~lulatiOf! of depl~ed ~1ls,. a1di!oo_gh~ciOlnm:~!~~~1~r!!.lS feVer'S'Cl t!<lim! ~ripl io!~. cetlJs fuJI ,cl]I'~!llp'm~i:Cs, f Iililccen C}c.Jc (fill. 3C we<Jre®~,vOO al LQ'L"!'Cf fM:jme!ldes til ce~is ,~ o Toall<!IYZC~lecen~~llr~.~~iim~ otfEIl:RA plctoo foc U!PF2 or ~"fle {flg" 4(;' 8nd~,g. 81). wcperfolifllcd .RNAnIIDrescCIIlOO :ina sIIu ~)'brid'" aIId '11i,g S3C), Iwr w.astllhe ~llitl: ·of s!!Ibst.udally Bccau~ ,Jasmid ~lR:NA.-mooiatedi dcpl(';lioo or i:mln.oll. (lNA':.f1SH) experim~llt5,f:liylbddizalLon, illftcfLc'i1.'.rl't0t81. mRRA. ~~Is (f~. S3D), .Fuoolarr·
I

l'J!iid!'i: e."p~~i!li£l s!~RNAs a~I'h'U di:fI'~b'iI)Vll SMG

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or''ITA.Gl1i.&UUAGGGI ~ Ife:pec~ ' ~~' 1iivetl'. 1~l!I1ImIl>WE!re peililbrnmedl , .~ _ l~~ili! I~ ,(trJ ~ M:A)aUlcl ~ ~~ . dmalu!mg (ro (j't(e(t [llNlA) wndj. ~ tiomo!l·,II5.' -diiilil1ifirtO--2-p!IJ m,~li1d:)IJe , iii· I"'~ ., ,. "".' . .. !'iI1!tdel ~'il!! ~ay.. (8) RNA.·fISH expe1nillillmtl> pmClfmedi ilIi! H~IP(ie1l5 ,afierilil,direri i:mmun;CliSTIlilii1:liIgi wilh antibOOi:es,m hiumafl Ra~l,. TlmlitA~gli1:a~al\~ ilil ~d., ~Rap.ll si~i1~Is, r,e [!i1g~eiil.,ai1i;1 coljlG!5~tio:l1 ofth~ two $i9m~l5: '~Eii'i,~r~ a y.ell!(fIIII' .sigiiia15 the II!III@rg@dlpalfle~~.(() RNAFRI:5H @\xperim~ns perf,olnifl!l@d on 'l!III@tlpbiiSe. oh~omoromes pr;epare~ll'ir:oml M~Js. lI:MA signaILsa~I!!~[1iI ,greBlil"alildl IDAPil·st!iinJed! ,[]It'iJ!A.is 'il Iredi,

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REPORTS
urF~.,E:ST~A,
z<l;]iOli!. Oir !IDle !N'M!) .~ NSJ9 RN It (22) (:11£.S2), Ill1Cas~ 9 'pm. . ItClmlil~ril'l defool5~s II1C!l lItll ~~~dJil'!i)'!CtOOl:ISC~1LlI%IOO
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~Hd!W! wl(l~ p@1Q!J!~~-dd~gcl!l:!iQJ!! 'of ~. ~ i'~!nl.dOOl~Qoo~~l lQ@ool~ {Fig, 4U)1 w!idd~ i51 ~pill: cgodh~grbf~QWn le~Qmericfuc~, i!1Chd· CQ!'!S:~twiih ~1Qre ~~erl!l roles IbrtlP[!,,'1 a.ld il:\gdlC six s1,lIlitletrinl o:m:lpOltwl.s{23}. Fhlilll~y, SMG] in g~t'lOlllile slabiiily {l9:, 20'} and :s{~g" SIDrin8,o.fmd3p:ll~ dqp!~elOOl for UPF~., es-r.IA, !llcsli.Y~ sim:ihw m~es fOlr .EST,IA. of
illrId. SMG ~
~fii!l¢!ind iro"!,!\c:aiI,OO,a.OCI!IIW!!l~.aJlio:~

of fuss ofca.nonko'l, NMi)" CQru;l$llmt~}'~.R.l\lA. rnlicl'Qant'iJ' a-iill)'sis: of ~i'ill$ d~I~Il!:d for UPF ~ Ifig. 3.
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pr~~!'is; j1ifCif'i!i OIll! URRA d~j},dmi{i¥1 from

chrom:atin. (A) IHe-La, ce'~ls 'werlE! lli1f@ch!(j: with ~enm~II!!I!lE!s 18'.xJ,pr,e~:o;iflg :~lhRN.As dl~irled!ed .ilJglaili1~t the im5~dited .SMG I~H~t@'in/S ~~ @mlpty v@CiOOr(siIi!E\I}, .and RiNA':rIS~1expgfilml@nts WIEHe p;il,rfomH!d to dieted ,c:IUOmaitil'hll!lSociiltled TEIRlfrl'A fil~ Irredl). Numbers 'inldlk<lile the' [iOll~ted 1rEI1l:RA.riOd fo.rr e<:ildh
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lliIumb!r o~ illERRA,fod" :1I:li'Oto' .2:00 m,~1s W1~re ~Ol.lli1t:eJlj fi'Or eamililf&tion •. 1!i!I.e:arns, (bar~) ,;lInd! .sD.!>(¢tmr biars) il,r,e from tw.o i'f!d~pll!ndi'lI~U ,~p~rimlffi& ~() FlhuMes~enlC1!~rti~ood U!u ,~Dltirln,g.afi8ilYiiiis lof the £a1n1!E!i (lE!l~'s; :S~1iI (A)ilild (8). IF'I, a Ili'lr,opidiulI'!l- iio:did~.
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If';g.4." SMG p:rmel'l5 p.uoted: IhUlflltilil 'Oelll!s fnllil1 I~oss: f !nlilre' e teklm;ere 'tra,ct\>. W TRF ,ilInlaIV:'liiis: o~ gel:!OO'Iic. IDNA prEpared ffi!'(!!W! I~lai ~ll!llst!'aJfI.s,ff~cb!!dwith pl~rniru ~j~re:S5[~g shRNAs <I:g:airut 1~IPfllll1dl IEstIA. or with lemp~"wdnr tOli!1mk. fiIIl)lliI1ibel~ at tliu~ Ibottom llilmrnre' the: ra.oo betwemtlile s1gl1liill

aJss()dit~doo the b~lk (Jh~tom~salii'!dl

~hrCsi~If1i!;1ilissodaoodl 00 , ilJltr,u!ljuomo:nlrll~lMmnerii'c repe:~, 'OT~, re~lIive' 'Ul~h8l~ralniSl'ert.ed '!ielk. Me8!liI~ <lInd S'l!)sare fmmlhrree ~ndependelilt: e-.:';jJ€:nmI!IiJIS, (8) ('()m~ iT!ietaphaJ~ and ili!iI'H~ecl eXlarnjie-s

'rll'om telomerk IONA-FiliSH lecxperillflBm pm'Ofmed 011'1metl· IIi'l,ha~chromaillOme{'lff.(lm H~~~a c@mls' 't'i~ted as· in '!'A~I. rel~tm(j!rk ~fiI,Y~()ll:S ,are i!il g~;~. i!;liI!dl I[lAPl ~!nOO !:hromJl" ~,Ollli1e!5 i!,fI~illl red. Armwhe'ad5 IPSi~ililt m ti~lOltierlE!·fre!8! IChllOliI1:C!lSOlililellild~ Irn~B). klt:erisks ililMatE telc:lilileril:rl7ag· e liI!lie,lF!ts·(TB). esSiocim~si~r~lom1fres I(A,SW$);.gs!illb~Loo't~ric IchrmlrlatTid Ibrellk I: IJIb) and an i'ntr.athIiClillQ1ioimilll ,hrmifl1lttd , I~,e:ak (Dr)., ,t'C) IIf'reqlll~lllcifl> of le~®men1ci3ibena:liOin;\i (liib5eIMd ~1iI SMGj,depietedl (Ellis.

REPORTS
TeRM m91~!Jjl~ ..l\wIi;iticiO!l~.~.yil!!!d1!!,Q;~sir~!lg ~1!<Y,\SCrlp~irnlQr OJ, ~uddh~ .Y'~_s~ oo[Q~~!Ie alIIlm:re 2. A S:Ii'IiI'iJ~fliilm!k.'l!' dtl IUingi!', AM!!, ~~. tJijjjt~m. T. 11.7'7 (ZD04t ,~. t;" ~~, J. Lingner, Oi'Io,~l.lffla i:i!S, 4]3 (2006). ~. '1'. 'lie' .l.l !"llI~" GeM~ De~, i!:9" ,UI!!;O i(2.000~"
~. M,A. "~o!.(!<, ~.~. Ilfl': ,~~~

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~eviateJ the 'WE C'x,cnOO by Iilile ~rulSCfibed, l.ciCF and pmvokcQ, Li!i!l<lmcm slli.O:rimling (14), ~1~~1ilg a mlcblelOJillJenc .RNA iiul.~i~,iziJtlg
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by ~Tl~l~i!;ms simiia!'10 It'heX:<h!iO~~Of!leiln~ <iJolhrlllion iflfum~'lc~!',~iffliid~ ls !llcdua!!cdi by Ut<e IOII~ ;noJlloodl~mg ij'i RNA (15)" 01" I[olh~ RNA X i~tcrf~nce-ifli,eclia~oo 'h(\lDCii'1J!Cllliruna:niu~liQl1 of l~ffiI~ In:lo:~nmie dll.:hoiill0!o,gOtl$! Jiegion tn. fli.'>il~m~, y~o;t po).. SMG ~mW.Jns~SIJli~ TERRA, <11 'C,h!!'(l:r!los,u~'!e e!Kl'l, O1I]d UPF~~mlESTIA ~)lzy8iC!llIy i!ll.~cl wimh DNA t)lll)']ll~r.lSC S ,aid l!cl~[N~rnse" '~iveiy (11, ts, HI, J7}, we spool]bte Id~8l 'dm RilmlfDaric~ !!lfoolSiudooed by SMG~~,plciiOll' cOlllddtcn,'i/c from, the lo~ of c()rnrrluimuo:~bctl.voon TElR'RA. aud key ~IW31~ ic<ldivitr~ dml&~ro ~1(inl~~p]L£<'!Ji(l~ and tmn~1IDI :hon'lO~is.
Reftfe!l1iQ!i:Siln!li NI:I~5 ],. T. _ Z'gllil\icki, Go SarEilZkij, ll.ad~ff"F. fa[li!~M, '5, f. Mcbm. ~roi ..~O'e!l' d'AiIiI<I dl ~~, llll. WlO5\l,

~_ ]1,.Jl.8a~f, 'i\.~ti!J, l!l';', :511.3\".W. [, '1jIJri~~ S~te 21fl\~, 2D]5 {ZOlIli :;i' •. lil_I~.'Gri~~d~li]lg~ O. M..lIp,ar:ldo, .iLll!!l1~If~hl~l' i.I.ltZB~kia~, o!-n ~3, 751. U'l'!lOJ. s, s, 8,. (-'!111m ,~.r.til." S'a.eI!Nf' 31~,lilSQ '[;Wlm. s, 'I.i'. LLmdl:il,lld. ], W. S~.oot.l'k. 57., ,~~ ~1!Jll:9t (dl liO. l r.~!Uwdl:, ' elJ~~let. l!!!ild 1,I~1iI,Ceil j:(i4, ~e7 (~ll K V. U. '1', .~ f!iiw. /1...~. V"99~r!,\/: ~M~l~~~ #~. ~w~t Ma8kf1, 1:ru. ~ 19$ (201)<1)H_ ~.;L ~liIU\'i' eli tI,t, curl'" 6ioJ'_B" ~Il I(:;lOIE). U .. p, 'fIt!kIU!lIlba.c1i t!i d1~ ,(".ai,1; J9:rt.i lit ~!j!lia:~fi~L n •. I. 8dlrn.j\~~~ E. IMUITfilld~,~ f.!IM ,20; .~91 (2'0061 1&. 5. 'r(.Ii:I~"\ ,Iil. Sedfl(, 10. O-lL!ar<l,I.. f.Mii~w~ JWtI~'. n (2'0003:11,6. I). G0t1i~ld,; L Untl1rlloLzner', F'" D', 1!'i((~HiIIi, !l" B!)rk~ e. l1<!urr,a~ ~O J; ,22" .:1%10 ,[WOO), 17, n Q. ~irdj' J ~~,. D. Wy!ilr'!!]\!H!~omi!<!5. Ill. Kipilt!l!1lli' Nat G;m~. 33~ ,m: (:ro~Ht 1L~. !l,LL 5. 'O~~~j~~" T. ,~~ I~Ogf~' ~# l.(I!!, 4 H~~O@Q), 1!,',l- (_ 'lt !\m~rn, l ~iili9rlleJ,GLI1't_ BIwl_ 110,4B (ro()~l ~D. K. IlL. Etl!JfDllrlaiugh,~tat.Mal. (eN H, !OIl'S, R.o[hf):. 21. 11,. Wlllirn1!iiln" E:IM. H:~'I, Ii. M •. !IId:, Mol ...C~{I, maL :2i'l, ]2:12 (2006), Z2. II. TIIlm'L~OO~' ~i.,li100 J. :t'l., ~484 U'l918,. t 2!1.li J. N!lil!d~l~ 1r4,.A.5Il!i1MI~,1. L,. ~e)!!fr,5;F., M:Ii!tfie.i:-M!IIMUtI; 1'1. C. [li:!l.. NO!. ,~. 36) 1003 {W(lr4}.

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21l. IL. t, :5Ii;~dl'~, VI. E. 'Gott!J!ilillli'i(l,\I, .A. Z!'&:f<lII, P~D~ Nil10, liard. :Sfi iJ.1A '91.. 12()'61 {l994!. ~5,. K,N~,[L P\!Ui~II,~,~~ A.Wu~ ~'Il~ 8,.~ [20007i. ,:6\ .1. fI..a!1:l1!l~Mi, 5il!!J<Li~. . 1I.!~~mlllC, !~II!i~, (Uf,;i5W1. 15, 1

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Sioblnaill
][O!le!

q~ie._"'Oernt (:c=!]oo ~QC1,wIDl~ illiiil tt-1~s !~liat ~u~mmd<lI1'1~roticallyless OO1!ive(eJJucellni.chc: s divide. Ce~llypcs .W'e QO.1ilslmimca wlddn 001 fI~es. so Ihall Mch new a::U diviS:[m~ slIDoossi.vcly displaces an oklCl' cell.clIisn~~ 1:0 11l.e qlliiGiOOoot ,0000irn .• Gells: ll]l.d'erg<n divi_~[Qll!,ctm:tgru!ioJ1l, and ,dlif[~lli<I!ionwt!e~lhey enter then~riililen'lottLc, ~I~~
tio!'!!, KDldillllllt!!!Oltio!'!! mIles,
!.e~atiVl}j)l,

M., BriI,dy ,.1 Diilwd .A" IOrlilll1ldlo,~'~ ]i~"Iri@'llIi1f1,gl 1U!,e,,1!-~ IDeillIDIV•.Wa rng.~ ]e:rl8!nfIliKIKI'I,.~ [R. Dililnelily,l Dl'ltliliie[~.Ma01!,.2 Uwe! Ollder;.4,$,G PIiIi[li[p,N.BerdeyJ,16t

a!ong

u~

li'ri:!JiiSl::npti@!1lat

!!!'Iild@rstaif!,(ijif!gllii!'~ ;gil:qli!~sitiooo:~ (@U and! tissu@ i~'IiI'tMty •. W@ :preSilIDtmtOlioorray @;rpmssioo profiles ofa liIig'n'f£s.olutioo .~Btof dew:&i:J:[i!lmmt.alil:im.e poif[~ii\iitli!~lfl 11!inl1gle ./k.abidOfJsit met ,fi:lilaa lOOIiFI!lIrelMIII5:iwmill!ll' ,0:1' neady ,iit~. Ult!)[ celli. ~. TheSie typ~pedliit tfal1l!icripielll3ll S~'gIil:atUlrres 'ofitrm ~rE!ldid: prre\lim!lSiI~ Il!Inj~fiJ[I1m celluilBlrr fillmm'olil~. A IOOlTI'1ipIJ[1iaI~Dn,,<1iI pipelil'1ieirlB!lltil\ij~ dGlilllnmm1. ,!t'Xj]!J'et>5iO:1iI pi!li1temll, that d'eIiftCll1t5irnail!:!' ~rral~~ljoillaai .simil .. rity [iletweenl disp(!rall! I)@U ty,pe5:, [!IaminaM expII'E!'~ion pa.ttemlllS' ,aLorn!) the' ~OO1'5 [~!:)n:!JiWdma\ axis dQ 11~)tslirial¥ !oon~~a!~ with [~~!iLiSily d~;if!~d d'~~pif!i!~!iltgl~oo,~ !i!nd 1111l'Ii1!1f!Y f (as!~,we db~M:ti @_ifPf@SStOO bCi'Nabloo aJlooi~ ~Qs;. 80th robust '!J~·f@~Yiia&ioo lat Ql~!i! ~~f@s<s:ron th~. ;atnd pot,mtiil'l~ ph8!s1if!~' 1iJ'~ g@i1@ @9(pt@Slsio!ilM\~idmti~@,~, b~III~I'l~~~dl!ilIl, r,oou"MI@iI!I1ods ti'lM comru,illJe these [proii~e5 de;mo:lilmam trarlsa;riptiGfilalm,!( rndlil aIfla liOm¢iE!!Jo! pmgrilln~.that demrle Af(J.bici'opIfs rom d)9'!le[lb~m.ent iln. both spate <lnd tiuJ,e..

.El~d[Jatilllg

t"'~~~NJgra!ilfl~m'gt und@flhi!

[~f(!IQfams: th~: rt'!!JUIDi3Itt!d~l(lp!!li!~lrlt ,are ,~u~[mly ~@fiIW[~OO ~

I!:imlDPflfH!m is '~~n~tro

SpaCfl

andt!!lIliil.

lO!lSHwiiIlill a:ds (Pig. ~). ~ll8e ceUs are Qo!]~~ stmim,~clI wililllill Inlu:~sefiles and 11C;'!.lI'ceIl!> areoolllL. at dle I:'OOt apex, 1'1 oo~,t's dev.el:OpJillGil'Il3ltlmnelil10 CfL11IOOtme];~daloog Iii,e .rool':Sloogi~tldiim8J1 ,rods~
.flIt [lre!,lij.'01!IsaJ~.~~ys1soom;baning fJI:UiJllieSiixmoo:-

oouival'ed ceil sortw.s; of~!i!

m~a!ys1s described

ten

{GW)-'markedi oe~1po;puiiatio!!5

ftu,oresccmprale.Un with rn[(iroa_~y ~resslOll I~rol!lies of five:

tissue ty'pes an.ddtrol:ldc¥elo;pamL£l1tal zofl£slndm rool (3). t1H.'.S~ ti.~ :l'IIx!. dnveloplllCilta:l ZCi.~.e:

p.ru,fi~&S revealed a greater 'If.ali'l$ldlPt~m~al ()O:i1l~ ~~,10l;1i1 :pwf!ile8 of lill!eo~,t<l!lone 0)..To Ilcc!l."alely de.wribe an ~S\iripliol;'!_"'lpiIlle!11S

ph:xilJ

d:nlit In ill\: l1.mt, hmi'l'Wiilr, :feqlllJ~'!:-S<I h~1.e_"" .. re""Oltl~iOl~d.wlil ~t Iillm!:prolfilC!l a~l cell ty,pes and,
OOv.e:lOp[tUlOI~1 :S!8!ge:i WillIDlan M Qtgoo.

ocwr

f!!lOV!de IMlsltl.Q!'gill wtfulrn1.1~:~on U~ AI!! ~!'g~~~ siAm:diug,afiUiLespatkd and lempomlCOlll1rct:l orim Oirgfllil '5 '~lfansQi,~pi:i,Qtud oomp Ie;;;i~y r'e\j lIIl res detaitcd k,1I0\l,I)ooge of its ~iIiru~npiio.1fI:liJ~ .s1a~('!S at 3. ru;oollJ!!i:OJ:I.~ fin f{i:rOO;U typL'l altd~do.pillleUital ~ag{\, H~~, \'~p!t..~n.l:,. !lthj,gh~It!iI!.~an.lhe fiM ~trl:cro~!'tay~basQd e7i;p~OWiIl'iap
(II"

Usiugdl{l

d.' ~~~liIo. .l'!li2ut. . jj' p il\liSJ'[!(~ L.~ regl1l~arod.lJiy

0. _

"!?

InUlin.'O~.l.h.M:~ar,org~.ll~. SCrJf'li.o:Iulil. networl::

trantlcnpl1;Qoo.1.

'!"'Q~~.~~

.•tel

ru ~rry~U

I~et-

~lllp(I!I:aiI.

Ihilit ~!lindm'li~~K!(Ilt .s.P'1110. d~\j~lO-pll'UlHlt, ;llclMding e'Vi(J('Liloo ·of

i]uOlTI3soel1<lC:

ooU-sort~mg

~:ilpres;$i(m

afilil,Iy:;~.s

1~ypc:5 <!rndj :~Q

fI(!!;itu~ti:~!l: ex[1~iQ!1 Qwr ~:teYeIQiPm.;n~<1~ tilll~ Iil!!.'ld: oo~dernb:1e c-~'!'eS!ldm~ V<!!rlai:km betweoen IndivJ.d~lal,f!IJOls.

a.s1!ligleOl'Stlll

ilnd ~pWme

·ofJleady .d~

."JrfJ/}ld(Jpsi;~;rool ,oo'U types,\\i'i,dl a.oolll;Pl'Lt.'ltL'Ollll~. lil"ijJiL1i~.iirrl!(j developGdI. (O<aJila:lyzJL'J tllisiil1ll:rtC'iIi\E Wle d.::lJ!aSGI,WC show' dl~,00000'DlllilIOf II. ooi.mple.:>:Ie:llm!"

TIle~eIlI1iIru'Oli!g~mlizm!on {l!i'd~,e Arnibid,apsJs fOOl. roclit:£c;sil.he ~]£)(ily of W1I3!~lr"liilg ill'! $p3ll0. Ien.lpotml. deve!l)~ut ThL'lfOoClliOOJ~SIJ;, of ~~ ~n :~yp~ tha!i.a~orsilnized!.~!,lillld.~iS. radial ;m:~o::, !1l!!:!~]' 'o'f~lioo display rolaUOll~1 S'y!'l1I~..e'!ry (Fig. ~and I<lM.e' 81 ,) 'C2), To a .~l'l!i: 3~roximalij{lIl., Ie ~ 1'OoiJ1:'so!aHon~:l SYUlffietJ}' p~nils: lillie<I1il<li~)'s1Sf r o cc,1:1 l~ Ito 'l'!c: OOilil'itK'il to one diriiioos:iolll!, !:be tadi~l~i~nt:l d:lIT:e:~rru cell lYj'ie;\llruiile fOOill n]~12

Ulnhfer:~t~yjOwrh~lIIl; NC ,27108, USA. ~1P~i!lern~~ <Lhap~l tlil~NIC ~'ni4, U~ "Ilillparlment a'l ,00mllll[oinfoml,;tlu[S, l!Jultii!! Ulnii\i'@r~ul)'. DJlrliu.1iIl, Nt ;rr7!!11l1, UStl. 5D@IliLJ~IiTl~rut oi {omlli'wl~r ~rl'ffi(i@, Du~e Urnili'llf5ny, Ou~lii'lf1rl"!NC 2no8.,I!JSJI. 61r1L5~1tUt~'(~r G ~~orne Sci ena:s <lnd Pclicy, Duke urniw:,rsity, Duma L!Lt role .2770a;,
()L!ilj;~

r!rnent ~ BiD.'~!I'. D!i.lIiI~ IlJni~eF5it}t OUt'lihil11!1, !1( UI$A. ~rFQ!grim iii! (,(Iffi:j)li.!tiiltiO!'!i'l Bi:o.log)' ~!l!~ 81.01njrOflll'!Mr~. ~ilS!:IMlte,lor G.!!no!!t~ Sdi!l~ce$ ~nd: I~~C~:

1D~pa

z]70i;i,

GLlIll! Oni~, ilfio[§ltMi,sli(s

US;I\.

'Pr~~1i!t ~dr!\'lel1~; £j,Qyoo Tl'loii!llp~ lil~t\J1eIQr Gt~L!'a rdI,. Tmw.er RoatlI.I~~lliC!LI. NY 14SS3,. U)'A'I'ro whor:n GJ)r~~~j:Qn~~il! shauM be ililId!"i!SSm. bl!lrurl!:.'p@dubJ~!1I

p\,,~!
E 'L!Il<lil:

801

REPORTS
n~~~~oo (S~."V>eQ1!lt~i~gj
g};P:~i9Q

e:igl'!t new GFP'·mi!lfk~dlIcell pop~la~Q!§[S I"]' (4)\ SJ 2 (4), eonUi (5)\ JO~.21 (lij, S4 (.f)\ SUC.2 (7). J2:501., 2111dRM~OOO' (tSibie Sin 'We oOilllmiillled ~llil~ willl ] l pi'l.'V.icrI!ls~y plilblis,hoo cxp~nlenl"l [PEn] [ (8). AG142 {S}.tlC {3}, (3),. CORTEX « 4)~ SCR (3),. J(D"f] {3},

IPfQf'i:~~~r g.1,.me,~ oolric!1OOi!~ ~;;l!ir ~1~5 (P =2J~. SJ.r, 3J!:r) (Fig,2~). ()ru.<lm<!i~Y,5is rurt!:lewi'!!c~,sed
dle SpeC_1iI1 oflblo~ogLcll.IPlIooe$se-s ilc'l&Ociillk.'d w~l:h.r:ooo'l.hair devebp:iilmnl to lilil.obllci!!l ooJcill.m. : ion transpoi'l., Vlcsiitlh-:dook:ing cillwi:ng(lXooylosi.'>.,

cQ!:i;§~~~W!rich@df]~VQi!!l"9Lcd. b~9.SYr!~~~;~ wuliJ!

au

J2.66 1 {9). Aft

{41 \VOL(n

and :$1 ~ 8 (4),] 'no

fonu a cO!lllpruhe!\'sl¥e dala set of 1'9e~u:hnc!'l1.S (mdl~il dam ~et) 'dlat ~mliite !~xp~n Oi.l'I4i
nOllGwrJawingooU l~ii~, I~hc Jl:i'f(JbM{)p.W1~root

(lI3hlt:: g] ) ..To ~oollle "h~wlo,lull'n.eil~a:lS1illgcs td1 thl': lmot, \.~ n1icrOOis~~I~ a $~~~¢ luoot il;J.t(;l l3 sootiO!t'JTWid~ '~cb~t!(m ('i!loomp;:l,.~!1\G apf!!l(Iximalely :5 to 5 rells Ol,'kli!!:g ~e lQngiludi~ OL"is, and we 1>110'100 Iill!,e e}!~~lressciori each by of unicraan:a~ (Hi)...TCI'I'lpom1 ,ex~·ton v.aI:ial'con, il~ sI.tO<I!lll:is1>1!lc been <icmoHstraiIOO, lIlId uaise ~a.'i imgCltl1l (l"'p~SiOJi'l.l'Ielw,ool~ gmm~ieanyidetr~i .esl (lillll~lfii<il!n<)e~n,clelt:iFmUVliL~cclt (U~.12),n~6~ fiM;(l fore, we<!(oo.~nicrodi~c!ed ~. fieoond root Ito assess ,cx.!'re._<:sim~ v.owiiarlion ~e.tweoo fOOlS h~de'iI"lilQp;lille:atnl livnl.':. "Vcflr:s~: asked! bow ,e}tpr~i.ol~bclW.eClD. imd)~v~dll!l8il cclll~ypocs .d'itTcred, by u,'>in,g 3.mb:oo;" IUl.1OOt:i~ ANOVA (aJiI.9i~yru; af vnrI9iIKIC;) to dctJCr~ ~~i!~ ~igf!ili~lt >dI!iff~~lia! ~~5iO!:l (Cj< 0'.00']) (9), We scloorod m nwkcr~i!1!es d];.ll fJ<!lOmC in.divkl.l!Ial 'Cl\l~ Ilypes, h'Vo ~btcSlh<l( explore G)!p.r:essii:mvariat~on withlind.te poocyclc" ami. [oI!lr ~iJiles~11~~.p:rotl~.c vary.illg de\'cloprmmt8!l illllgc.s ofxy.h':iW md! I:lI~t0illl1 (mhll1: S~lOlllrmy C l~lJlPI"¢VlIQ(1lSimt~~13Iio:n, d1:t;': va.<iIC!!!br o~]1 tYr~ comlllinihe ~~i~:l~ mYJlloc-r of cllrio'tiled ~~Ul<~ (fig. S.]. ta'lMe S~.1(31. fU!~cti(lns {lfiJKlIVid:u@[tcM ~.ypes.h.ave been. 'ClllIU,OC(Cr!_zcd bygclI.Clk Of ~;h.ysio~o.:gj.C811 sum.lo..~,oo~.lm cOlrup;il.dtC:lIsive 3n8~ys~q has ·~boo lItep.ul\1t!tive['ultcl;mlS of
each ecll t.ypelffiS d~fiinoo. by ifill IrlilfLwriptm:ru~; Wi.':
1!~e~fQre:~x;i:lirl]i!K>dG~~~ Ou!OOl1oSYGO) 1.~!111 ~ e!!rich!~~em usIng U]C: 1Jiy',pe~eolllCIrlC d!stri~ llIulilon:, cOlTooti~g fw n]l!IUil]D~c lypotl:i,wis test~mg~'Oinlbr ,cel:lllllru- f~llcdol!l (H). Anlllfllbcr gt'irl~ have also been as,ooc~at:ed! w~lilil o~ogiCld M

hiosyudi.ctic I~me·s 1[1"- 6..12F'6 (~ab!e S.3H. Almlher wilking example is liae '@DlnchJtltool of gellGSinvol.vod. iilil. defunSliil, hMn, sud ox.idflJlivc; 3JJ1m,nkmtiJiltlJnl:ici'.¢ ~dei:i!tn'~dtP'l,-"d~lid~ ,and/or ~t~ ms,~UIil~ il~ I~JIli~~od~~i~: [P = 4..:rr4, ,tiOo.\'UIl~rnlid!¢ adl~liIii1C; di!ilUc:J.c.otidL:l Iphl(i~lhal~ 8;97.g-"l. :B.23E-<:'i (tab.le 83:)]. ,(NAIl'" INAI!)Pi ~c~~~'Y {P = 2E. :~ W~ \\ie~ ..lso l!H~te:d i!~ldeilli:lYirng iOO:!!l'" U~. SE-'l).W!jh th~<!dded cO!l!~clkl!]oe in pl~ ",p~i~1~ressi:G!l,~lter!1S that are specific our method, we Im~l'mu sed cm;~e:h.cd.gellie to two or ~rnore cell ~pG:s, and tI~CMrt:1'e, 'we catego:r:[~ to infer' ~ilile f1300t[QIU, f (D'ther oeU o dev..elopOO an lJi~slllplCrvi~cd SP,iU(NIDh, wi~ilt~~ ~Ypi':S(tab~Ci 53 lI:ndi figs. 8:2 ki S4),. Ofpru1ielll.I!I1 dm:vD;inaiu.DlC1M~ve lJX~i.m~ [piiliue~s aeross c~ll. no!.!): "'!,I'~lfI} .!(:yI,~!tt:l~lh<; i!fl 1IlQ:n~(lrij~oowliltie zo:n~ lyp!';£ ::uid ;'IIOTIS; d~~~opm~~I:!I1 t~!1fIi:l (10). If ~n¢ U)J,l('~1l'cre 1;,'!m~ll1;ld fo!"lrnn81.Wlio!~ WiitiaMn and OOes !l<1itkn{!'Il'I.'the it friOO'i C)!~~O~ P~I~""'~ iin a I:\)io~ogicl!) OO'!l!re1>l1:, dleICC are tv.'O ,!:\l{jHsatiOfl, RNA bhHl:t~g .mdl~-ss~rng', and ~cm ... '..' '1 .~~...5 13~:1I~ umOll!<!S "D_" ,~~ ·S·~. \l!.!;;~~II].,. ~.. y C, & ,) mjel!ods d\ilII:·catIiI :~denliry ~ili!entThe farsl CnI.I(16), {fig. 8:5). Sltmn~ oolooaili.zati;(!ln, of ~e lil~ IfiIx.1il.le!>8il~possibhilpatrenilS. HO'WCNfr! &iv(i'l]d.u~ two. el~IllC.~ inf:i9!;lOno:id biosyn.dlesiis I'll tlim It.mgll~1.8.iIildlOQEl~I.exily of Ow I!'fIi~mlllilili! we IIJiC eenex h3~~ boon d.GttD10Jilf>!ratlld. by l!IitUlIii.l!mj)looa~· Illoking [or. ~~~~ nmlm~r of :I'Hlil1ll:1m':w(ll!lkli 00 izatuon (I1).\Vc: pfO\'idJi; ful1thtlw ,~vkft.~ fo:r m'lmcUlb*, li1~. cQ~~!.1eItny~(1)lr pi!~lin{:: IUS~

cmic'I~l;!d! ~.xf~ron

gf WOOf Q\r~tle nVl:hVQ~o:k!

.:sr.

,._& ..

,t.;.

II

Ol[;,

..

profiles of 19 ~ruor'~ll!tiIy $O~dt IGFP·

~re~~:01ll

In!l.~..~kfCl.!!ff.~ .

,~~

In!lal~rt'@c til1l~WI:!fli!

I~yzed0-9, 23,. 24l Th~ CQ!~Drsassm:1a.te.d wij"

fJ!l:Eli"

eaCih m~f~ef ti~~I~~led

~~e ,dewi.op:mernIaJ srn:~ <lInd ,oollbP~.!>aJlIlp~ffl.
ml15:Mfe Sill!lilpl.ea aIDnig

ThilWm ilafll:l'!l'~~se: ec;. s

~I:QS (r@t! tilf!@'s~'(1,0]. (iC', rnm~tlniOlilnllil;.

~h~

I~OQ·t'~ kwn g.ilW.d)ilii..].

or

l;l'r:oo(lSS,L'lS ~~lIrpu~h IInierQllliliD'ayGl(,lPmssLQllill]aly~

nmurnled d~e,Hlel'alUror{}r $.11icJ~ <ils..'>1;lc~atto·I1I~~d fQr~e<lt~, dw:t fuJ:k: g~~eslo trn1~~clp!ig\!!l<1!1 nelwO'J.'li;;s !bro~!ig;h. d&SlS. g!~lL':

Vile. ~lerurQre

e~CI11c·~t ern:ichnwnll(Ags.

52: (:0, 34) (},o),. Two

wcrreob'Sli1tveCi :ioI.'GiO' terra • 0 I. _I RMl 0001 ~urEIMi.. ROOT} elmcl.tmool: Firm, IiIiIcmajOOiI.y of ~iIilri.QtDOO.tUI1'1l1S DO ••• 1• • 1. WOlr5fEU:' weroa.~ociatOO with. ul:'id.~."..i.doo~. eoll Il"YPC:S,fIIl:lr.:i • SUiC2 [11'.HLOlM fCO' Cl • 532 IAU PRetroPJ.!lW/!M, seoomd. dllM~ GO tem~S8!f;Sodfl~oo W~1I1 mul__ 0•• Ali'LWHWEM H~'CJ I~:iple tYl!~ I~~~nl. mere .gl;!~m! b.~g~"@ic.d •• c~U M (DflIfWPlNG fl'l£M)
fi!OOe~iC:S

illltcl'CStingb:cnas

(e"g., ~1\}"isglll<lIOJ.'Cl:lvity

eud mem-

bir:;;u~C ~l!Qlli zat[oll) (f~g. :21>., and lil.bJe SJ<!Jnd: fig. S2:) (14). AS.fI measure oflh~ roli8ibility of Old( mffiinod 111 £dcIllifyimlg eell ~.~m~lridled: gt,m~ and. .of m:ur:!lbmly '!.O C(J~!iily aimo!a~l'l ,",iiL'l~(lg~.caI.p~~ to a cell iyp!,l~w~C(lmp:ar~tt

• c:
ell.

.1.1.0

.0.1
DO

5:1 is fMATlJWNG X'fLfI4} I .J2SIU (.:saUJ

a ]iSll'I;,'!: g.e!'1;et'aled"fgenese~lric~~ed

i~l

rool.hair

c,ells,',dd~ a ~revio1i.ls.s~u.diy dlOii('prof'ne:d roet hair nlOqlhlC!§elIles!S. ~I~aooo!r:d: wi~h.9~i;s pubiis:hed, n~.i»rl (IS). we: fiooillldl [OOil hairecU ditlIlliMcnlli2lcI~L'On~~UI~, kiill,ISG::fi" i1iild. fN~.u'i'l12II.-1ofi<;GiIl~m.g

GIl2 {NON-NAJRatu .A.GiA~ fQUl~KfN7C~lIlm~ PlE'rn 1 KOW!~ELLA J .1[:] 'bHef.t.Affl'fA t ·flQar CAP~

B~~~:;~::JfPMJ~' \ .to
'.
. .... .
t

CJ.

• LJI.. .J 2M~ ......... '''-'''' r. JO'1:l 11}O'LEM POL f "~fll!r\il~ 0 .J:OS"·l (GROUND n.s;Wf)

S17I'PHl!OEM

pa,!'E

REPORTS
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h~bo!!l! dal~ "V~~ 9'f~. mdi~1 ~. 1b!'lJgit!!&!~~ Q~~r, se d11!l, poottive~~o;;~~ ~. dOO1~!~t ~~ioo ~. (p,t£, 4, A oct'\!. :B,il!!la ~ W~ req_cired,.ru~,;'!_ .~~ fe~lII~ing, S8 cllJl!sl~ \'i.\lt:e aml~'yzed {J(}) (fQ~(b; S5)~By lJus ~'edmdl, fokb' ~l 11Ie.reru~l'lnghjgh Ii\'!JIDve~11Ib III, the
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intmooniOils of,expressicm were VUlll.mlrned. tn. 3, I~t ~11IlP (!!fll:hc ~~roc G,iml2lns:ifllloll {lD),IOO'I, (Fig:. 4B aad fl]~®t:S4:;'Oo.;.d OO~bbOl~~ \\~~ fwnd, b~\"'~1iI ~~5io:n b_un ~1e1i)f'.m~piIi(;»'i;;d. f!'!!'~lb~ imd 1I1<e ~reftcl.6d !lpatLtl'C1T!~1 CN;pressi()\l [lalll'!:!!:ts (fig. 4B SI6), Om: oOlil'tplllIllimiial pipeHnerevl'S!~ooa
<lirlcll [I£;.

2lUSprO~

sets \~

ld~IfIl'Ufiedsmng a

Ublg;I!lillI!l!.~ly ~\!} 4q A ll'l1lI'L'iI'OO, of dw;lm'fl were thmd 11iIa1.i'lM dw~opn'iCliilllll. :z~ (Fii} 4Do), cg1l '~. ·at spOO:fil(: (iI~Q~(':mud. ~~~,(lIiid ~ vAl~ ex:p~tlJl~' ,~aiti" a si!~e ceU

InOO~

,md f:QTU:j.~p~~OOQf Q~j'IQ~di!Ug ~~. t1Q!lfM:~g'S. ~we~ <lb!enQ iHr~r1!.MYE4l1!lclfl trnIwr:ilJrnon facIOf'r-fe,gulalloo. il~""in 'bjmywlli1:esis Inooul£", mnauxin ~nSll fllou {AR:F)-lljgtlI3~~. IlOOdu.1c; iUl, dJI} oo:l'!Il:t1dlill, ~ld ti!l.lO W.R!Ky::regtila~oo.
i[l.liIaii'c~~.s:lltdiff'~11l ~\i!~Ojlil~!lj!al dlt~

IlIlJ!nM

oil'dOltUnrull C!(f~..ooil pil~Ctus, but lheinimjaldarta=~~ing Sl~p d,irnt~lfIa:rOO.. ~oo®illNU: 'Were net ~~d (ff tl'!i!ltdl5p~oolowL;l.:'::~tl'~~l!iOl:l. 'CawertL!1.~~P!'ii..~(!i!~ 00 bi!W}l (,re&eni or liIbsenO~<I!]lI!eS· caiXll!fes c1iffe~!iI(!l._~1S «ge!lie f'~Ifre!L~.{ln diSCMiJ.edJ when a!'mlY".d~g relative C'.x.,m&'>tQIll. Binary p3I.1mlSfDil~ bod'! ,(Wa ~ts
Wllro sllIlper.~~ll!posed lISi,i\g Ihc AND ~ogica~,

liP:: 'U!muglw!)l~,de~Qpn~_3J time (FIg. 4E). r:;:(~j}m. dnUl, ~tOO wiJ1hoori.1oefl'ilfim. ,~ lios Meil,albll.'lm ~l'l!'c 1mi~j;)~{InallPm. ~.YtiJl III higlil ~tia.l aid '~nwrnru ~llH·iJn. '\\~ ~~(I~ldih.()l'! b1: ;:abib to ~. Ill'iif!S~gfOOPS ,of~")t· .~~&e~ 10,i~te!'bmlg(l'ipiiOlllaJ.~~~!~ lilies. Cis-eI!Ol!lC!i1I.e.mrld~!l~!'!J: witID!~'!cooxp!\..~ ~te PlI"S .c.-m 'jWfim cloos as to u:~lre<lm ~s.c
lIIll1lm:y l.IiUlS'CnpWIl :footors:. VI\'C· m~9~ymcll gcflCS asii~noo 00, all IPflUCII;tS [0;' !.'llmalled c~1CniH7!niili

po~~ (fig. S~l)o. l1~eaWliJl 'biosynUI($~ [i1~tlJt.y~ ooo:fi!n'!I.>d. :b:y <In 1!lIele of i1~ iJ/teMd :rl"}'Pi()plwli R~~~kJ.~ionI (I,j.m'J) lvrYB4!TI<liDnClmL"C~Jliori footo:r ,supports idle validity of Ol1l"rI:lCd~ool in i!lfl, filifiiilg Ithle.ore oolllm (1,0, 22) ..MQi'fe ~hisliicalIOO, m 31gOOitIlIiliiiJl :\11i1ooklbc abrclto c:(in:mldldiii~ MlSiiys~5l :i R id~fy U~oo~:I1Ip;l~~l ·of 1:FdiI~!JtLomt regul~ 001)' '!f!~ules i!l1~!\lb 'fOOl d~~OJlment T c '''"",,11 ·d......''''~;1 -A' ,~;, - c· llliIi S ~Ii "," .. ~ _Oge",,"T, _Ie '.... a. ~_!.Gy ~!UJI!li -'-c1i:l'-

re..OO:~ll!tim~&la. set. ilolh high~'isJi!.i!!ndl!'eVise

O'~

view ofdll(;:rich. a\'d, Qomp~(!\i 1'I'k.'t\wrk o:ifIll9JEri,= lim].1(lpngt<lfw$i1l« 'lIl.riie rnU. 1~.1fJC."lIIm'Im~~ral

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radial, ,@/)(pN!$$,iolf!lpa:t$~m
Fig. 4. Cr.mflb.tl1lmg r,ad'al, arid longitlildinal exjilres$l;{lfll data t'oidemify gene ,exp.re~io:!il ~:!ilspace and timf' lI!I~il1l9dDllnililiClilt ,ec...:p;re5i5io:1iI pa.tilemlil.'(.A

and ~) er lwini!fV l,ogic i(('~

~" (A)

Radiji!I'~ ~is}a!i1d l~(p!!l~di!1~!l i~lv ,~S)! ~

z~. eloog:i:lltli~nll,olile. (I).A 9,DI r,epreseflrtatim 'of the' (.o:riHMrli~,a~ ,alHm.m 1111 "l'-!:'0"" . ~1~'.1I1~At3§Q5150 tr~l1OOJIipool1iall G~Pfus:;1')r:l1 OOli)firlTllS tlu~1S~li~ru&i(;lfil, I1111~'eto E) All '@'i(plfeslO,nvalttu.es.wer,eIl:OOr'!lE!rledw billie ry r'~r;esEliltD:IIIi, and MARIKER ILJINE'S IMARKeR 1D"IN~ MARK~R 1.1 NE$ wm(1,inOOlIllIl:ililgl me logrkal AND :operate~ •.Ptrr~ence (reet) Or' absem:f W~ue'JI !!)f ~1~~,i'Qf) i!il tim radial ~~~t (x~iiS) ~f!d tp!ID~ I~~f!;gi~$p!arndi!ta .S!~ W ~is) ;f:s, indkattOO.¥(!1.I}gw~fi!dka~~ 1il;ilp~El'S:ri~!1lround ~ b~ d~~!,!5Jets,Mgr~~f [i!il!l! lillnd wliigitu:t:iinflil ~ertJiOOI ori1l~r ife .iliS: in ~gs. 2il1n(J1 3. ,~C)lIii~qi.ii'biiS exp:rE!5stomliilil all cell w!pe5iillna dmlc:pmentastages,. (0) .&preSlSiclll'i00 ty initlt~ mMilli!tiOiil mille. ~E~Iexprl!!'Ssiiolil~!ili1lml.mot mIIIe!ll amf cen types except Il'iIlIamrilil!£1 x~l!rrn" .. . -

pM!t:ems ,are wmblilfle:d by Ilor'ld~tional i1.d:<iitlioo toyieldl ~I:.mve: en ri~~l!d pMks fif e..'I:IPfes81YcInlrby ,(-ell. we and ,aE!M',etoprrne,nml. time. The Iheat rna,p' pr,ook!si;!liIenrlched n'llattv,!'! p~k 'tJf' ~,r,~stofl' ~~'~h:~ ()~ ,and:mo~ WB\il:1(Iyiii! tliie@Ii!'oodLm'lflis, a1I: ~e ·~llstal r'egion gfllle mmU!liIlflib'i:c lJ!Jn2 ilnd

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REPORTS
@...~pe~~-" Qfroot d~~rQP~TIe!!'t!~ d~ (~~,~! wi~~
b einteresling
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13 •. I',
M.

~h~,5pat~~ <lnd~elwjX!!rnl

i~iI'3.l\'5Cnp~iQlflSJ~ool.,exriJty ~a'~ tmdk:d~cs organ d:evdopme~t im, othGrmlll~iodlular o:rrgarllislt1Jll.

R~fl!~elnli!:i!!$O!!!dl N'ot!!s

'1'. R; CI'CIIMIIQr" c. C!ynlfillfl, .J' .~. Wyri~k;. fJJ"infimm~''c:s ;!1 4411 ~2:00;s,J', 1~. M,A. J~~S, M. J. !l<!pi!lo!J4. N. 5!IJfr,~I(, fiffiflfj, 4!J. ai3
(WOQ),

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fl.. 5'lilt So.::. 5111. ,9. Metlit;d,

U, 4"9

w.ilh tli!i! Nf,r:Nlll)iMill{!i~ OlI'i~F. Vi!IM~ 'far di:lumii:! ,oot1I[>!lrrril1lg ~jQo if!ii1mElnmeml. ~ ,~Is<IIMI~ N. Pl~all.1lII~. J. H.are., 1:, !~LcfuelHlIdli, Ei.5cbe!EiS, ~flId ~mbffl'5 Ql '1lI1e Ber!!'~ Itb ri!!f _""~ 11M!'!!\<IfI!!IK~pt SJU. reu\\~ P!!!t~! 5\!~!~ ~rg!Q ~ ~!~'W!~ fe~~p,f«Htr) .~ N~'ISri~i\IC~'~md

:1. ~t li!!!.!i[],e, E. IHL Ill!o.riii!l~lJrn.. Pr,t'!!:. Nbt,(, ,&'t.'i!lt Sri_ u.SJ11, 1m" 490lt (2:0ffiG). 2:. 1'\ N" Bernfli!!f, It Srn~r!!l, Cwr_llfot mIlIl 111:813 '[~OOIl~ j,. tL $i~~li~, £t'a~~f.c:~{j~ ~;rn2" 1~,6 '(~OQ3t 4_ l~- ~~ ~'oIlf. Pt(J(_~- Ma1, 5P, ~S.lli,l[k;!.. ~5 (2O(1:Ql', : S" S. ~, ar,iIIjj~, 5, S!!l~, ~_ ;5, !)~IJ!I~" j, A, R~i:!!~ki, P. N, !!ernfl~, !i'Jli!lrJIM:~i!lt l43,. ILl::! '(21000). ~.t, I~!!'I~~'et til.,}. £:(Po~' ~~. ;l4H (~OQ:5}, t, A, 1!l1lia!.!.E, T~mt N. ~tJa'. /'l!\!l'Jr' (;~ 'U. 3,09 (], m, ~. T. ,~~W)' ef (Oil !'(Qljr (.:[1 il7,,~90$ Q:ooen. .. 9, M. p, lew5qu~ ellil.. PlDSB!cl. 4, el~,~ (;?'o(!:6)., 10. ~le~iI~ ,~r!d:Im'lmoil~,~r'e ~¥i!iLab~Q~ ~lIIW'rLiI!QI
I~te;ij<d Oro 5{i~lI'e' 'O~!iil!le'. U,. E. l{~~if, [l, i1Iillll.'lll, '11'_ Iilaliir, :R_,~. Gi~n, ,ftJJH :;l,]',ti,

is, M,. M'I!nge~, :5_ ,M_ de,

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Ja:[II!r,w" Grlli~em., l '"'_ H_ rllurrrar,

,IlUl. 'i~!Uppottf!i!l' by,~ IIilrth Il:irSl:hrtrili f{j~iJmal,~~H:h

~1'lItt!, bill Ifl'lI!lJkittoF1!Jj,~Irn'!l!tIp q,iiH(i...lLi!ll, ilai'lll\~~d li\ !jlmn ~UffW' In Ccirnpul2tlmal1J.\olill'!:ulu I3bl!!j1!. 1I111i~ 11,\11111: il~ 'flJlllded ill 1!Jq,e IJi!I1 Il)f Ill'! ~F A~2a10 gf<llnt 00 W P,N''s, (o]~J'54l ~OO lbot Ir4Sf 06iL:B~04 til P',Us. .mll lUI.

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j. ~i.. 546 (lOM), Ill. Sa!JB\1i!JfI', 1m.Wll'llkfl-S1i!J1n1f!(1\, PitrrJt t 2:7. J·7 (~oa). M,.-t.Deq)li'lIru.!!.'1 aJ ~ Sdl1Me 311t4.,.IS9:~ ~to@6}. s, Vim~ m~ eI' a,I"f!I:«II,~' Cell I'. 3D~$ U!:OQS,). !, l'!e ~!net ~ . .rr{" ~!1L'glQpmell!';!.~~" !6::!4 t:!!OO',l}, 11.1E~I1S!i 11,.It4au,z:. Ba'·J~ph. 6, mo.Yllosm.tltf{:5 2:1.hl!59
(l'VIlG),

Sgp'pg,rti!!gJ Orq'~iMM5!'~ri~1
'W~_f.Il:i!iJ1(~~~I.~W<1(!!I!1g!ilIle!l!J!ll!M3:!!'()!5&'51I'3DlLMKl Ma!ed.als ailD !1i2[1KH!I~,
~igli" ,5:1 lim~2:l!

,~~s.tl:illl~)" ~', H. r!.~a!W!r. ii, II!;"j~ [l, 1)11It'n~i!J"SdeMe ~:U. 5~6l:!Q~n_

Phy.;lrJI., 131.253. (2:[101;)', :n. t(. 'BlrillllJ.iil!fifl .!l'I' ,gj'., Nm•. i!t!~/Jlad:~ ;2,61-~ (2:00~)" 24. M, 8Dflbl. ~Thlit.illllade!1', A. P.!~almnerll M"T. HiliJ,iier', ':f. Iiii:~!iiutt".lMlr.tIJ'e 4!2:6" 18l ("oon. 2S. We lbilmk. ~ OCr!1lImm f~ pltM!!i!i9 '!I!e~~m, ·~Soiit ,?Ji!!l Il. ,Pillrild «If!!! II. N~!ilrl!e ratfleo RMlO 00 wt;l :5et... !1f!em!;ie,fl; !;II t~ [l~e Qmi:er f~ S~!!IS IBi1!1iIW ,;!M! l E!I'od\rrJlr ~Il!~ 1!ful;Y;~!I!, m.. ~~ r~J~~ta~

I', t, (1!1~lI:Iaet (11.,filOfrI

't'!bl!!!! Sl t~, Sl.1i

1iil'1lf~~efll('Il~' f~ld~r5 si to :5&

~~ep~~ 2: lO~tQl!!<~,OO'~ 111),1!,I;l6AlCiefl~e,ll~<R66 a:1~ne;~f!)1;

:M,enin Control:s G,rowth ef Paneteatic p,~Celll:s,itn Plrelgnant M:ic,e, and IProm1o,te's IG,es1alliotnal IDis,betes MeIUm!:s,
:5.aly:ajtt K. Karmik,l H'ilJil1llll~, 'Cl'le'Ill~;1!~GIi',tenH!W. McLelll n.h Je~)!lmy l. Heii~.:l!.~ X;llIeyi'ng 'GII!I,,4! A!llIlolie,w\i'.. ihallilg.:1 .Ma gaH Fo:l1i1:aililiej! .M~d;tiille~. HI.,¥ien,.l;51Soelmlil!l 11< l!i'iiml•5It •.
[Dllrilrl!j Pf'~!il(!!ilCY,!I!1aU!!TIa!l p.amlr,~lsWts !:j,Miillb:! n:1atJ:h, dyilalll!!fc physio!~gical~ dem:andi. bllitlhe l~edlil,m~iSlm'ti '~I!iILa.tllngl CJidaiptWe~meJt gfOM~ifl thiS s@lililllflg~are 1~lOrly l!!iI!~@rnoodL 1f@~E! '!n'@. show that

:~~lelsW!aood dm"~ ge._~.uf(m~\~ledI i li~liS!~. l$d_s of Mi.m.l nill:.NA Ol!xinl.'uin d~ c~d! ;lll't:-gm!lKo/ ~~3 ]" D~, G)\ jh"n~~oo lO,pq:ortllI1l1l:!vt1llS: by 1 \welk allcr bJrtJtl ofd:m·pqpi (Fig,~" Farad. G),.By eOOltm9t. we ,d'~dlll,a~ ,d,(1lacl ~h3ng~i[l ntlll1mnalE>~~I~L:lVru ocutRNA maoodll'lg nVRlje!. 1~tCa!~!I~~~tnia-·] (I\4!LU),. a p:[tQll;'lin IIhM assoeiates wid~ !llCrnn (Fi.g.IF,), '1]!lUIkl;:,alre!w<J!loo

maronw

mern~ililr ill p'rotEin'lpr~liliSly tililarac.telii!edas .a!l1lmCio<:ril'leWmOf SIJJ~pr,es~:If andrranrsm1Ip1ilOO:ilI, reg.uLlIiOti. mnlrnolsisletgJiswtlliJil'l IlIffign!l3l1Ju 11IIiInil:li!'. IPlr'E!gn1ii1mc:y mutated! pIIoLif,e;rra.ti:ol1J of mamrnal PBI'IQ[le'alici!ilet I~,.(:e&filial W<lJ> diC)(1OOiIpanl:ed by ~MOO3dl IS!ret L~l!> ,ali menin aMI its, Ilalr~ts.. Iralllll!?1ri1k 'IDIp~ioli!l of IlIIiIeliliilil i:I matemna~ ~~ells PIN:!V'Mlei!i~·Sl& explllil~oo. ,lIiIi':I lled W' ~YI~lrglycElI1Iidlandl im,ai'iu@d ,glucose ~ra~(~ Ih~~lM!'!i~~~aWr'~ of g,~!il!ll diab~, lP'r,~.mn,a lIi!~m~(j!~1 r~g!!!~ (:llf ~gf1';1!nqy, Imep~,esS@~~llet Hil@!1]fll@-VE!:Jsaf!~. stfm~lilWI l1".(@n l~iir@ratiDn,. 1ih!!S@ f@silits @xl!.:md ~I!.I' !!!iI!Rmalilding o,~ 1~@Qlili1lJl~5!il'1S II!rld@rlyintQd'Eab~ pathO];j,mesis illllOO r,ewallil~al tng@1ShlFlIDl~rrapY ,(ij~b~~ ijlfl
..(J)!.· ..;: IPI;l~.C~ .•. k .1 'cr.~Iw1 t .•. ...~.,pru.)'S .•ro.!.l. i.! s1.el i .. ~ IUdcms "'rid :Ill.!!rr~n~(J-J) Sll!gs,es~ dlat adapllV.1.'l is1.cl cell :growd] lis ~ moch!iil.Inl~,t,n1i fa: IIlll$l!lrlng lin (llR'lhciliic 1lmI;llinooil~ lPf!.'lgtl2lncy;

!!1kI,1 'eN:pressim~ ,co!TCSpm~dledJ with increased p"oeU prodirem1ion in :1I,mlc.milil islets, MG~dllf~1IIIonI0lill!i ill~ ~OIm l1:1:1.]d~!YllmlWre~~ prollM oomp.l~C()l1lailDimlg Mll (9,. .Wl n~s ootrUpi]cx pmlnQt~ ~1I1nlell~y~a1ioJil. oJI.t~<;'I(lUlC! H) : Or! 1~;ne4 (H3''''4), alll ep,igcne1)icll:wi;:~:<;8ooia!ed will! tm!!&iri,prion~nJ OlCI.iVC ,ch_l'l}_D'!m!in, MCruLI]·
SlI,Oi"D ,ofp2~11 and J"Jlf~c (heroalta;. p27 ml:! p.l8), whicb. Clx:oOe cyclilWl~lnmm lkim&'£(COl{)
d.i~.)e!~._

l~....Msm!le ~~ ...jJ~iil,li~rg n.~.i~.lm. .ex.~ .. I ins

(fig, S,I B).;. i'\;IitCi!' jpW'll!![lnia.u!. n'!al!mlii1.~ .~~U 1ll!l.5.'l OUilcl body lwass; r:ot1I:'lled. lO l~rqlELt'Gl!L1n levels "fig, S 1•.A OlImI .13). Toasooss Inarum8~, islet mU, proHf. ill p.11ysLolo,gkal gnate mwked. hY~IlC.1:e~dI ilQ$ll!~ilD, !~i:m, \ve pnlfofilMCI .~1tcliililg stiJI.di(')S Wm~,bmI~la.dm:naml .~nptr ... Sliud'i'L\::\! ~ \villl~fl)ltJ! (2', .J) 8ilpdw..tymdil~ (]'hfU).. ~-(;tln pru~ifht~otlilt{:ro[L~":d ~. the l.lYptld.tesal'l !ihatprolir~ml!ion. Q~' ims:~:~irn- ill p~al1l :Itl~e !,lflJtiI .~.~days [l(I8tcoilUlll (diJc) ~cJcti!!g i511el ~-censLslh~pril!~dpal :vnec!~J!~i!l!\~. al!di!~(l!l declined '!o lJrep<.I!I\nn liev-e!s (r~£.1 Ii. lQ ()\f j ,~'''Cen ~!p<JI~~I~ In IRgJ1JIjIJl:lY, !lilt dll.'l !l1IO(k;C~J: (.'"lhus,rnlill_emaltslet~'il ,e;I';PaI'lSIOlil Ula58 1l!!ldi basis !IlffaCI.I~;talli,'iI\1.'l :n;unemlll !3-ccllj#rollifiCrntion IS '~JJ'edyI,ll1llnic: inm[o;:'. IlInoQ\l,If.1I. Mor:eo'!,~r,il is l!IIn.c~.earifilll1plli.rnd: :F:ID~lasla a[ Ihe Ina.rull1ial piltlLllliy,5) flll.d Imll1n0rl\a:~ ~-oot~prulif~imt[{mleaw t(if: oodl-u:ooo islw ~[I. p~liI3l1Cy is fllJ:lilunJoomu of c.odOCr.i:ul~ imsuliliil ~.e¥elsa:nd! g<~Lo!nal, cli;ili~i'::S (4) .. 'pool~fl1imnioCl ill mui~l;ph:: enducrw:m noop~3N:i!l r~ l'Q h¥¥~j~ ~,~ '!'!eC'fil<l!~~5, ,coo~!i!~g H~~ {MID.J ~1·,,·h~!~J!Ci!i!loot syI'!drm:ne d~d~_~ It~m1 hllet ec),!pam;!oo •. W'e. '~al'Il~~~ ~~ll :rllG h~ by ~l\:!!rOnQm ~l!In~ ·gf .~!Ie p!i.Y!~imy. e!~!!e
~irresillll!lll

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by l"!!i'CifoM

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~h,,!, S';aln~ilI'rdl C!! 94~ 05, UlSJI. l[lE1parlli'mmrIQ~

S;la~dord Unimsit!f, 5tanriWKiI. (11. ~M305.• USA.~lD;epilrt·

meiiIt er ~I:didn~' (Onoo~:I' nhfision),:5t!inf~ UqW!f~lty,. SM~Ho~d,{~94305. USA,

S!iI~tjj'fOOiliIllilJli\ltDon or,IW:~fl, whose p:roteinprodoo'i is lwe!lil.t (6,. 7)..ml~mice .fflJ!tlQ:. bJJ~nl!ll~s, :u~a~iQ-nr;g~d ~ pall{)Jogi~. Melll lo~pmll'ilU!rn 1fI~i!lfOO'IldocriUl(il ltI~iJndl,!d-ililg :L~tet «1:1'~~m(IS (7,8,~,TiIlU1!l. ~ ~~ pow:d1!iled d'lat [physlolagicoll d~es,i!l! Men)

'i'lhl'.li~ ~'l!iUlor~c:o~!lFi bu~ l'ql!ii!.~!I' to tlli~ 'r.~olll:.

"~"Il'o' !'lhom
(Qrr~.spood1i!ilG! ~.I!ungkim@.5~anf;orrlA!<d!ll_ sliiouldl be addressl'd'. E-mail:

,e;.,;,presskm Intl\lht!iegui~atefacu~llitivelllater!llai~ ~dI~ ~m\1i,fd~ illl jp!'e,gl'l!ill't!:ly. Inll'Wl!lIl1I.Ghistolog;y.

"\~Dcm,

bhlllJjj~,am. iiC:8~.",~~:l'm 1\WCi'SC;

OOil,mpt{ial

iX'1,yn:n;~(3ehaii~

macli.cm (RT..JIrn) stndies of

llIl:]lfibilOlfS ~ililfflpl'eventisl~:prolife:rrationl (11-.14). CooS'i~len~ \vJJtffiI ,t)tlr lW!f!1iv1.otllll :~Ild:img.~in i_:';!~~.liui-, !~ (U).reduQ;ldi~!e~ !'llCiU!] l'cve~ in i~reg!'li.'l'!11C)' .. afler 8 ~)C wcreao0011~panhxl. by red~!OO:d JJ2 7 .mdl pi8 IfI!RN.A~~d. 1~"I~fI level:> ,(FIg. ~G aodflg. SIC} amid. as; 11't"llll~OO bycinrolll81irl,il:runElnopl:'C'" cipiwi,QlD, (0iIJ'l). ·~oot'fCaOOdil~ls. ,of l~lCIlin ;U,~ mmCil:ryllTU~4~ialed wiili1~.pLr al{! p 1~ {.fll1l< IH}. 'Dt~ 1lI.OO1'DlIa~ nl~inurnl(,Ml~~ <\'Uri fun;J(.'Iio.ll redliJoedp"~cn.m~ch~lct p27 ,aII;'d 1),.18 ~~km .~. PNgf~a!~] ice, m To dcl:enlltlll.'l '!'I\'IIIe~lel: adapUve maik:ulIl~ell proLifemtCon mtigtli ruq]l!Iire i:OO:umd .. M~ll wpms. $ilOi'n" '\W .gr..llOOlOOdi mK:{lihat ~enl')]uoo. co:m:wllooal .M'm.!J etptrl-.~I,~ 1:'1 ~-ooDs..llalb~(lIlic mre~l.cing !],~~~~yd!1-ig~.;~edme!ti!il 'J~~r 'OO!'li_I'Q'~ Qf il1e ~etm;;:.ycl:il1e~')O!1Be e1en~H~ (f!R.~·Mcnl) (1'J)W'e.1I'e gclle:L'aIi,ed ;iM'KII 1Ja.1'ied, wiih .~ni.Qe CXJEs.> slingdJe ~l,'erne te@:'ac,yclun.e inmns"~!iliVlior ~I\:) jill. p-cll:lls rullllKJIiM! by iIrlem'l.il~~.illptDJlKltCtt' rW-p) (.16). ]11 bi-lrd:l:~milfcRW"rlTJl, 'rREM¢.i\I,JmLfi;: {~vL'1l!(,ld flliitetd1\l~I~~ir.lIliirm (i(fdOK.yqdil~ (:00...;) aJl(J!.Msd'fA ~i!l:il:~gl(l19~e; mE &~OOl iii_1l;!I s.twl'lul<JJ_1.'lS Il~,~ ~iP~ioo of .i.... knl .lilRNA. <lId IlWIilin~n (mg~ A <!11K!. 11)" E.."'POO!ll'e ('!rm:~ 82, nUl' ,or llffi·JWl!-)t1 ~irngl~ fransgt'nic~tiL'C 1:0 D:J:,;:. dKll. rnlOll.ii!idoce dllilIii'i§~ fu mC'ii1.ll~\lek 'Cfi,g. S2~ A

REPORTS
ll!!ld Eo),.

:~Mefll miee oonli!l1l!w",!y ~pQ!led,goDQNiil!Iil~ U) w~ks of~e, we <iI!.'iected il~ Icvtlls of Mall. pl.'!. Md: IJlS nrlRNA.11l:m, ooliJditimm.lin,~ dltcli<m Ofm2llfnil~ ~.o::ng s.lLltmJaiIOO,t1'i{~On afkMv.ti n~~~iI~~~ g~l~ HOi.~Llit,TREM(fJd ~~i~l i!~ fI:\1iI~ 01' vUlg'tii ff'm'iiiil.e IYMJ!fi~ ~nice did !wl .<!I00t· 5~n!!,1l]lt'ii!!OOot gJuoose ctnUliO <ng· S2, C ~o~" i!i.dk:ali!ig ~'I!!illnu?':~~"J e;!;.~ ~nmrm a1\cnncdldlInt d~sru,pt~~U ful\)1iioo. To assess d1~'~~llI.eDlOO;!l of ~~lmti,1}mi~)!i'" :
l]

~isbl~ isol;;lirOO!\v!]'g n~~

Q!" vIrgil!

r~m~

~~

<1i!~

i!!.~!'ioo '@'~l.~~i!!Jg ~:J~!hli& g'~tI~ ,dclive!), .. 'W~ b]gt ~ldRf..pm ~!WW8is fe'!i'eut!~dll\atMw,!l rnRNA anillmili1ill~1s ~ ill~dlilill islens :~romDox--e.xpCiis~, pf:Clgmlllt ~nl :fulillOies millpflil,:i':dlo controls, and im:imJ'
1~i)~W~i)&'Xi!l~6m1~iI~.Ii'ilmt[lWail ;1l;Cma.~ ~tl

glyQ)S~ ~g. u~~.km,. L.:J~ ,ge!le e""'P~'O!],.md! :~!~1I,4h .t!l rl.1lll1k~k; I3Meil ~in1J~ sWlmg 111 m \!I'Ceks of age. Utl~ike~~l8'~bOO! preguElIlt OOlllm~Sor v1rgm. IfMaIiI.]fmlmiks ex~ to .Da.X,progilfU1l: ilM'£U~,

pM~!I!]i¥!e~ (rig. S2.G), V\fe ~~~

rl;iiltil:ll~ ~~

ID~

andl

i81~ pqn~ffi'o!il ~~M~JiilO1~i'5

{Fis:. 1, A Ito E.

~rn.l>s:ioi~ dml~g'~.gilaJf1ey,

,,~

OMliit'OOuslyGx.~
I,iO,Dtli!ll.

1~lo-\''V>~k~ld

~M~I~I n~l~ ~

r~r8

:~d I!g :S2Fl p27 @.dpI8r1lRNA <'11(;[ p~{!i .11 ~en~ i&lds a[OO!ii,ereascCl ~Q ie'l'& ilidlslingiUls!l:able froml 'I.hose iltlprepm1I1iliflls;lclS. (rim- 2A !Iud. t~_ Sl'F), By OOil!mS.t,. ~:lRNA.'1Cilrod:i~ liis!ffJitl (l'ltd~ ij~'i'di:ii2 (1ii.:~2)tGli:'IlJ. rulld .Piiit.l ,. faCkirili d'll!lt ~~ ~nrUltCtL'(:IJ,\\~mIl I!Iid<'illgOO in

~~~'!OO~~I~~1U !i.\\'(y~ until ~'ll\l~}' (Fig. 2f <l!~d~g. J,. A :iiJ'd S .8). 'CO'l'l1:P~!!f.~ to W1Hloois', mear! gl!;.!cGseleve1s :~!'I fasloo, jiMefl ~,IWQd}mmii. ~were also sigui~ CMt~ 11i.g£lcr(1f(g. 2G and fi:g, S3C).~~~taleal gloo~ ,enlalikm~S~lrl~~1i'Iyrevealj}dJ ill~rOOglll!}~ !Q1~~~oom p~n~f:U 1iJvl~~~Jml!~ QIa Dg;i{
BrdU~n:su lin
M~Jlllnfil1Sulin

fiX! adlibifui.t~ d~~1,. by 9 ,~,whi~

~t ~.'i)'~. 10':1 ~ , m 6 !iIlke SOOIflPied pet fie PQ!m). '~lilI:~

if), I~m ,of Iw5iltUili(g11lel!11') ill ~SI!e,tl ~UI(Im IIil'OIl!PI1!;glil!iimt ,(B(~'allfldl 1.7;dpc l~ffigmliUmice, (o.m'ill11d E)

IF'ig. 1. Dynallfi: rl~!awnofi IllIiIeliiiilflilIld iIli~fI:~!IIes d!llugl ~~ltatM:! islet ~.i:1i1iliXEg;Iif!a!!tt:!lfJ~@' (I.) O!.!aliJli!Hlm~or a:rd)iji~0fI~amlll by' ma1Ermt

and BreilJ ~~
~~(m

melti IiII (red~i lliiiSlm~rom llIloll1preglrlant ~[)) and lI!1.dp( lli!'regnalilt:~m~ ml:'r!: (10.,S~~~

ofil§OOll

(~eJl)a;m11

I~ar,50 .1IIm., !lAd G~IReal~~

~lJRillfliitysiS afMeIU
.tIIc;i 1m!

,m

G
11m!!l1lln

gn.:d W~ [!DfOlle!im (G}~lICm bWt gool~ ~ 'Ii~ lililckated

HI '~I~~~~;;;;~-~~~~~;;;]i ~ ~~M;;;,oo~p;,;;w",,~,;;:.W!~J;_,'
~Q
.~Q

~;

J~

,~6e

,J: ,

If

i5oI!aJe:lmum.l i5le18. OI~(hIP iii II' ~ II" in IP Iii 11" ~jj II' II.. Ii' I" IP III II' lb II' iJ ~~ liJ 11'" ., IP smdlie~ 01' ll1«IilJ .,mel trim2!hiyt· prlJ ~I H3K-4 tissod'almMlllI p1:89AmH fJ27' <lIndp27 flOm nOClpre[!nant, ~r~nt. and pm1paJiltImI lII1'atemal.iili;llEITs, = ~, ' ,6 mire)l. I~"J~; hffe'i!llnIi in Figs. 2. to 4 <l'represented as, tine' means ± SO. 'l<p.< O.ll~. ~. m <lFlrp <O./{DrL AI>. .an~lbody; IgG. ~IiIilIililWl~gkilblJf]i1"lG(; Menliin, @IiIWmeniilil A!b.1Meth~, ,l:lllilttiIfl3K4· Ab; In.,nput DNA; IIP.ifl\l1flunJQpi\oopitate.
__ ..... ,;;;,;.,Iiiiiiu.iiiiii!

~""',""""",P,;"N;;"..!9fl:,;,.Wi~:;.;,;U~l;:;;;M~~· ;;;;dpe~· _,, .• ~b' =r= ';;;:,!;!'~~;;;,FI,;;;;_I!m~ ~ ..~(~,-4,::,,) ,iJ,·_lilllL MoO.., M>~. No"""._~ ~ .1iI""~~ ~i> .... ~~. b M..." 1Ja!"Il
Po~.

IFilg_ 2. P'h~o~pE!':'l fromlll!lllJ~ ~~iPflEl!'S$~o!i!of m!ll!i'lifll ~n i~~~; A

of pr,e-g.lflalilt mle. tA~Westem 1~lot illliNlly.sis of tine. ]ndlicatedi

I~umeiin$mi~ ~ ~llIIi!I!II'!: (ooWI Glnd prlegllililliti3Mtlill 11lIiI~1ffi,bolhat :17 d1pc, sad fmml' 1!iI'on,r,eg)l'Ii;1int (I)iUltriol mice. !'l'!er!!nli==~~=~' 1~!1I!to IE)I Imm!~!iI(lhiru!bgkd~ p18 tediCln Ilif IlIIurl~in 11!IiI!1!1111111 (red, aJrr~Wh~gdcS; ~ii! (0) ,!'!I!ildlg.rr,o!!'ol'J illl (EI]flfl 1~~8'I: pulls (Qlr!e@Iil) 'rllfCfilfl p.regmmt c;ol1tmi~.(8: ill11d1OJ ,;lJl1d pf~!liilal'l~:~~M(ml('C.aiil~ lli1· EI

IUllike. oolihM 17 ~iX"Stlil.e bar,

!:iij~m (B allld C) ilIHd2t1IJmli OiIlild I~I. (F) BloQd gl!J;405!e l~e\!l!1lSr Iii ~,Mm1 IlfIlIi!OO '~~ljiC:k'I <ilndoonfiiids (gr<Ly~fildl adl Il'ij)..

1m

itU!l!lI

Irue, .!I'i~,aildl.

Qif'ld '~IX'~ed

t't:!

D~ be-

pregnafiOj

IlGl' Intr~~~tCDfI~l~ gh~oo~wlIe-ralfloere~ti ~f DOiX~~lPo:sed pr1eglillalm PNlenJll~~Iack~ ,ilIli1~ llil'[leQllIalilt C!ooh(d mica l(gray), bath at 16 d ptt:{~ ;, 3 to ISmki~ pelf grllup)'. Caku.Lalediufli'il llilliider tih'e !l':t1we"was; :2S::I:OAi!lr~ I.Imts ij)liAieli!ru' ¥er~us,:22.:Ii: lilnl.i' <:!1mB limit; '(,c;n'itro~d, .P'o;;:; OJ')!05. (H) S'~ml 11115Uliiil comllmba,tlliClI1:S, (II)' p.Il'"(reafl1c ~~Il II!IlIBSS, ,an!! (D IBrdU 'inJCOI'IPOtr<lrtiIDIlIi1:lj!die.s 1111,16-00 :r;jl..,dpc plr~ln'lIlIt. JJ,Mel11] !

'(1;1 =: lOin !!i liI1il~ per g![I[}lII~.

mice (MaJ(,k). ,pre,glllilint ((J'rn~Clls (g!rtlry). ,and nOllip~ln1lm: (OlliitrOlts '(White},. DO:x I(r:!= l1!o 6 Irnln~e ellllo.~pti')I. (II: illild U liJiI1 tect]om !1!frl:!lMl) ~f1;d ilfl~yl]~ (gf,~I,'l!li ;I!Ii ii1f'@~naJ!1t '~I:!m~(!( (I() ~!ld p:rregll'ia;m ~1iI1. mioe I(L) .at 17 ,tipe. Scale birir, SO .!!nt "p", 0.0 5.,~W.P< !lOl. ""~p'<:0,1001..

i!lIW~ ..admnllli~tered @if ~~ltI (fI~.

REPORTS
11"1'91,,:1. ,Stat5 (lInd BdE! Ir@'£! ,~,[I!tim:'J ef IDel1liril i111. u lliJiiatema,t ist~b;. (A ,gmdl B) [I,&emOIl of IniS!.lliil'l(gelil) ,[lInd .StlilS bed~ 'inl i~~el:5, :r~m l!IIonprogM!1Jt (A) ~!ild Illuegllliliit I) ml~•.Scate lbon, .50 1J.m. ((II Wefllelmlil tlIJeil: StiltS, lIiI rid! IBcl~6irll eXltaC:1:5 of malierni1!ll islet. (mI) ChIP

d~OiIi

of S~6,

p~wh~

D N"P'2.,
,------------------,~ I~ ~

~ilJ

!'lO,Il.lI . 111'"

~a_

lIelS

al!'!~~is OI~ Bd6 g~da1i(lfil withl th@, MtjJ,t,l:8,. and p21 loci ililisl~i 5D'~Cllred :r~ !l)II'I1)i~fI(irrit. prJ~n:mt lli1IO~lrttulirl dal{ !it, iillrnd past:Ipal'i:!!Im dt.a.y21.rnic:e.IPrim:er Iiii'm!' '[PlJ',2)kM Mml ~, li!)@et'I 1~es>OOiEdl I!lr,evOCIl!I5I.v ,(7). (E amdilFc) IR&'!l",tiirmll! IRJ~('R (!iiila~ of4ll!nt pW, and p27 (Ell Of Bd6 lliIIBIilA IrMI:'l (If) ~1iI ~ I~I to, Illlu~~,ctinl (b~add,v,~hIi(:~~

NO>!.b 1111 IF' -----------------~,

Mm

_
HI

. ~@

.'

!19~

~6,

~~

In

Ul'

IDi~

.,
'I'll

III~RL
I.~ .,
~:

'"

,~W.OI" ·to I~th p;ifW.WIiI

,uta pr,¥~OIiII2
3~~M~t~m)\

(g~.ay) (n':::::

ll111D1J1Ofatian ~,.~.

R~.fune' R1i~Ram~

p,~

or,6cl6' '(m or Mm.l" p18.l¥KJp27 ~J!4A IeWtll (H)im ~sret:; Jromp;olidrl~_s:ed badi~'ill!Idmmrol.lIIfIla!, (WtiJ~. (I) 'QmdCa,OOtiJo~ B«IU [ill pml~nl:J&'d (bI;!d:)' Of .~00'IJ'(Jl milE! ~lle)' (Q= a miie pi!rlIre'almelil®'. ~p,< o.OO,""P -e QlOO!." -p -e OJOOl.,

(Fig. 2.G). Qms:istl!.li1lwith,dlC5efimiiJlIgs, ~l1Jjn ~I~sl!.lin ilnwre t:001LIC£d.mlEg!l"lIll ~tmll1uoo INc {Fig. 2M}. Otbi:lr~il:IOCI~~\in::l~illig body mass, ~ilOOl'8;ze.rufldI aVl;l<'l.~ biflh ~ig]uof ,\M~ und~li!1gyisl~ble rUt IiMm~ Iooll~ 1!IiIdWllools (fig '34, A roq.ln 'INOn~lMjh g.est~~iJ!lal~~

'tIP~.

§:25

~
~

;~

~'1!!:i, .:... '1!0I

beres. ~"llUl giucose oO!~!IJ~IJID:l<~l oiflcn 1~l!.!HS to IUlOO'JiIW.atlW dIDlivmy . .u~V1Z£ ~n .~M:Clll loollIDii'S m~IJo,:(.,bloo;j].gl'lilOOSll; Imr& dmrrea.'lOO! ,whblffi1b of I~h~pq~ and '\'IerC iltdlsill~gaJisJhab~~ fmm tI:ICISC of Og~! nJ1(fid:~ Wig. if), T~~l!!S, I~Me~l "li~ I~"-

captlu~f~liI'es Qt~U!f!l!m I~tkmal dJ.es. To !!lvt8ngaE.e wkdwr I!"l'!p<litd hmiUn product:Lal](ij'~retim mi:ghD Uiooedic bypoil1sl.d.:incmia in lIMen ~ mioe:, lWC n'lOO'lllBld ;~nrulin mn.lLmt <!tid: OOcr:rJlD:illIJ i'illlatlcll$t('t,J;, hmUn C(j~tml~r~te( cell 'Y.-m sl:tni:l!alt inpn.'gI;)nIIlMoo]am OOIlm)! m!1;.e «(~ S4D),.l!k~:w:I.9e",il!ll.d~~ ~i~~ by P~l ~ .. i:'i!~.sO1JiI'ef S1i!"l'!~~.ttonwil.l g1!i100sc (]t. qi!~~!,e: (fig.. :S4, :E :~dI F),i'i\i1S indL'ldngulslllOOile fro.iIl} iJllll
omlu;ols. Todetmni!llc
~aU;OOI

and ~.yperglyoomliail:l !fM~~l:I'Iiooll,dhdoo.

~r ga;1nIl\!f1a1,h,Xp!.1i!~_mila
'We

or

of ~~tfrom.oon d:ea!b, Ctdllecth,,,GI,!r', 11lI1e$L'lftlildtilllg.s STAI5; ;xx.I1LII]1Jl!.laOO m. (fUg.. :3, A and B), IfMoo]alOCl cootmlll'llioo. [m ~esi; '~~~.~l.mJt!IT!iQ:lllof !~!~~~ ~let !VIle. :~t- rud levels of p~'V!!Q-STA.TS and SlATS OOQ~ 1P~"!<l;~t I~Me~.!. !1~ice la~e~dQf.s;e~'i.m!l; fk.'eU .. SToATS:~J~,db!£mtlllmQ:-8 "-21) !~nm W'M s~!:6crn~dy n:dlwr....! CQ!l!J~~'o 1P"'~ ,ell; pe!'!ll~ls ~P1!~ i3,«n i~~l!Stan llil p:e{l)~f!cy.. p.imCy ...l~k~~ ~rot:a.cti!lltl;nd! p!~uillllaci;0IgI;.1IlS am 1K:!l:Jl'IOf'o1lil iI~!kid J~rr;ueas.edi !rlitl1lQo.'I1iI'Qlst1:llCili al~dIIilildisill'lgUiiS:oobile from sc lIld fig, SS.Al. f:ki6 InRN1A 3ldpro~iH ,oomm ioo~dI (fig. 3C 8jYJ. ~,-ccllllil85!l il1p;t'CpartuTIl .~mdm:~ (Fjg. :21} ~lnl ;regu.hrn:];s ofprcgnan.c:y Inlml s.tLnltllflle.~~lprol.if. ~l{in (IIf ~rogtilm.t1 JfM.cnl. I'lTIiee,. EmU S"ilU:lies n.";I1eaDed: i~lionin ilTII!jCIl~. and h.uilinrn. isl(Jii;(17-19), I~tr~ r;ug, S5]]:)SI~d OrP ro\lC:3ledldlf!OOti riLI)I_Oed. ~-ctlJ).pro1iIMl:ioo. at ~.1 ,(Fig. 2, j l~fI dar: 1liH(l~ldrll"~;~ fi;Jjj d:teiu nni.tog~ni.c,rnfed i~ d~ &i~ ~.lrnjt-~rt~\ftl(G~()i (21, 12),wiih 1'1vlenJ L], 111m, ~iol'i'l~ ~!,i(iiorl j]:W m~I:I.p2j. :.ncl d~riJl'lg~gm~rtr:y (Fig, llJ1, Mi..~IP~ooof!lt!!i;!16 kBown Wi1l im,!~i~iid ~f~1ll1~1Th ,8;gnn1iI~ ~IH MIN6 cel~, a ~~lWi~, i'1Il~HOOIil1i,""demrcd ta"ll)e~ p]:B lcwelS\V<ls ~~!1~W i!lI~M'~.·! is:1.d.. 1~!1.g to ula.l.e5 }'.Wd l!'l ~rCe'llJs. La.cl(l.genic!toOf!t'io!'!e.<J s, srJ~nllllalc p!lOspilOl}'lalkm ,aI1d1liJ1.1c~' ao;;U!'~l\Ila- Hlie ~'lSi'!,i'e 1.0, ocmT1;i:!1 growIJ.l rues: {,I.1, 23), im~~red .tkieil ,~fml!. MoNoWf. we dicW not W,i1S ooffidenit Ito rod'ooe C'li\Pressicm .of cn.m.,geG,{Uli> de!ecl dirteRll1l.oes in. isletoill :apol~IlsLsin, J)Mku lion of s~~im~lral1&il.llceJ! ac~v<llurofnmlls::~" tU'd Iiiofii 5 (STAT5]\ wbbb 11OC11~GS ,ex~ocm o~'~1lS .Men.l" p18, and.p27n.1RNA (fug. SSC} MtImQilllCi". and oo.1:nm~lillilfiDte i1nioo (Big; S3Gl .:;u~1i1ii11~ 1[Ib~ .&1'6 (20} TniJ;ltltS, firm, If.lttWi~jju. ilIIl~@.,i1U~lMi l1d6~D'l.~.Cii~ ii1OOtwOO, ~iK1i~iM. ,of kfejt.ll~halrod.l:eM P-c£11 mJ~bl pM~J ~'I:Iiolil net dit!ll
'n1il,C;plli~~

~-aGnGXp:lliISl.{ltl!,

,aa~ru

Ln).

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P{Q(:. MJIItAmd. .Sa: tliA. 93, 694 7 ~19'9,6)' 'Ol. V. I.. S,gy!er~ O. A~~!iI, "{. I-I~,L !il.S~i!·~t, 0g.1!"e ~, ,aU!l {1 <;lI')61 2,t l Mi,yazak:ii it nL, tJld\Xrlfli!lrn.gy Il7, 121], [l:W!]" 2'i, j!j.~. ~l1;malil!. N~.V•. l1IliagFoo. 1i. (,. Bf@ij~', It. I.. 5mrtftllom"IEivlMlflli1!1!i!"",. :l~t Hll:~ (,MOOJ. 2'5, r. :5hffiQO e'/.ar •• SdeJl("e 2:99, . .11? ~2QO~. :2:6\, t !lGlI~liiI. ~. E. ~itl!, S. a.:onner'it'lliir;, fll'd«rfnt!l~

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([ooaJ~~g ~.mn~ism ~ unlairn."rn S:~t11(l~~ 1. IF. A.. ~\iaJIA!;~I!, L AIlirn. F:. n~, ,FlIil,~81. ). OMl'~. • P I~~ e~ie ·of t"D~alCCI !~~ i..<:1.eIs!o p~ ~m'tol. ss, ale: ~l9?i8). 2. II,.it. IP,miQrn;" 1. c.. ~nl~~, It. lfi~roflll~l, ffltltlClii'ltJicgy !adin iIld. pmges!e~~ ot[e~w. d~"~FsJ!.tfeJtJ, ~ 1:H). :l.4S~ (:l9?2). 1',18.p27~ atd 1k:l6 ~ptCl>Si.(lnp1Wokoo :by jii1Q,.. 3. "=1... ::;~r~~~. 1[. C. !;l~ij~,ffl!tm~~. N~ ~9!, 3'!):I, t"i.rt~~ 3boo, (As. .3. E ru:id, f). UU!!,nrultiple 1.tt1t~ (l!)\iI'1). Irl):)Ulsli~em:cly ~00l: ~.,m1J. Mbti ~~'iioo. ~. ~,Erllnkl!r,. :5.1- Ger~, It It. Simmooa t@~~ 51. U'il9 (moo), I3cl~~t:'I'!l d~($iri!. }~n1., pJ8" 3!!Id p2''! s, IE. 1iIorI'~(I .. f(, t:'!r~:t1, S" W. Sdll!!itllllll!!r. MIJI/till! 1. 'l!.6i9 ~F~~OI~ provd\)oo 0, '~:rc~~l in 1\.11'\'6, OOUil, or (1999), in ru~ ~1W1'!<1n is~1s (!t~S6 1[0 8[;1 ~oo 6. C. iilT:I.5~m. 8, Sl!Jog!'IlHd..K". 00019. Y. U"~.!WIlI'~, til!~e 'U!ldh'lgS.~ldshm~\OCIhal Men}'~~<li~on by M. UIJiI~em,lr;j!I-I~. /'rJartJre 33.2, as U?8a}. ~~n slgI1A~ilig ~s evolul~iomJri]y OOI.1.'Wf'vOO. 7. :5.. K ~LeJtll,,""'m. ill, Y.Acm'l, Sa" 100,4, l!89(2£(l.f1.. ~. II,~, !i!eit" :5, ft, Ka r!frik:, s. ~- Ki!11\, Mro\!1..~!f. ee! :Ow" To, 1t.(lI'.t. if laelogen !>~!81i ng 'wall SIlI:Iil"K::La;'il I!:O ~it!i. :i!~. ;n~ Q:OO'~l. lredu.t'£ .M.'(!j.tJ cx:~aorn arndil'JCre~ p-rell ~roU9- (_ 'lt !-lilI!Iho;!~ ,~ (If, .M~ (eli 13, 52] (2.o04!]I. cmlloo :iJ!vWgj ,,~~ 'mu~~~dnlL~ w~I'I ~~nlil(ti(: nco •. I\, 'lfllkiJ!r~lna et· at. ~[ [e1~_ .Biol .2111 .S0619 ~;lOO.::l~. a '~lic~U!'IlllS 00, dl'lli\fli:f prolooli!'! lOr ,6 days {Jj)1 n, !j, It Ii'.li mil ~·llr1.",Ptoc" 'MJA Al:r!fd. S'lf a,~. 16~, 146,§~ l2J)a~J" C(!n~~redwitili! islets fmnllwhicli>iu[lfiloo.oo~l!'Qk, 12.'1'. A, .Milne .el ~i.,'f1t .. /If.alf.. ,4{·oo. Sa. U;~JI. 102, 749 f ili!j!e!iBrrompm~oocn~l]fusoo. mi'cc: ~~~. afhurfold. {~(1.5), i"~ilil. J1c!6 ,exp:r;essi.mI.3 5rPA! roclMc~()n of B. Il W, :St~!'1'!:W ~ (!~,,''(l_Il('~ .. ~60; 5:r(l~' ~ZOOOl'< ~ .M}ml, p18, aildp271111R.N}.,. Mdia 25·;[nklincreaoo l~. !).. S. ff~lfI~rlli ~- IL. G!i!!;lI'ire)', I), J4 Q'8r1~ C. ,!)eng, 'Ir'_ l(~rnfig,MJl (ell .B:WL Z~ .sUI (2:0001 !if BmrlU IllYlrpn310C111 by fi-oolils; (fig. 3, ,G to wjb lUI•. i!NalJ!<n~1!! .a.rlil m!!Uloo~aF!!;J'li!i!.a'~e' as :H!iPlltlrl~mg T'hl ...Shl!t·tr,,"lr~~~ i.~~i~]'!~ !.'i~di~:rntltD fM~~tI~l ofl .~dlljW~ O~IIM. m~.""f;~w,l ~re._~'{)!.l :~. vi\i'o a!ld ~o ~nWl~e li6. 11,. ~, liI'Ilit .rl'.~.m .. NatfJJf:4ot3, B45 (201llil,~. [Ilfdife!<!li!:I!1I: nt· <KiI.u.lli5~il ikrelL~Adcll!licmilll ~l.!clic:s jJ'. '1'. C, Rteljll (tJ (]~~ in(foctfntt:!.1bgy i:it2, ,B79' (19·~.~).
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o5dlratmft1'!!llailil ,~.aniOO,ccteriil 'aln 'be ~eams,l!UtUi1Win ui5iIilQl tiulrftptlteililr-' <l11iId KaiC" Ile toltll pI!JOOl~.rn~alhm 1E:ve1of IK:a~(,o~Uates,wiiimil Irn-cadh:m period!, but. the m.f(h'<lJ1~sml IJI'Idei~g '~ ..~lIIStl'inedooi!lillatioo rel!li1C~l'IS:lInd~e.ar. We Il!Jaw sIiIOWIiI,liIiIaI:Iioor Ibtrms .Oi~ Kale I ,dliff~g if! their plilt'~~h()'Yl:rtioiii1 ~!a~ !i!ff~ m1'!lii1 ~!lrrOO pa~m grislii1gl oom 1h~ifl'btr5f( ~~!iliI~ ~''i'.,!i "'-,""4:-I!l"'h~.'~ r"'..... OJ·! !I'!!iI!'" "lr! __'~'I.. " m._,,'!!n!l.'!iI IIJ III"-IA.• ",~!iI~!I!"..-d :b·..... .. ..,t.,.~!' ........ ~,d""'~....,· " lIti,~: .... IL _l""IIIIr .. ,.. !li&!. ~. ~1i!__ .""~ ,,'Jh!.!""'I~"lIi"__ .!i!~.=4 1It~,"". ~~~i!l·Iit'"'.-~....,.i'I,ii~i .... _~ that g;oo wth~ pihgspl1.oW;Ii\H~iIilh,iliJts,tti1e ;G.cti;v1w of KaiAthfOOg:hifl1ie;IToiiwOOwithr l!<alg .• p~kllng 1h~ It!rrlooiill.fuedoo(k tliiiIlsli5tlins osdllation. ,tJ" 1ii11Illiem:a1!i'talliilode~. ''-iortmfl]neci by experimleml. ,dial:.lI Iqua:lilti'IErtlli!K1l.y ~proolllrns the ciuam!al"l p1lioo amllmm dimru11iljf1 rd1nlilmits ,oflilile foom :phlJS~a:fol'm'ii. KaiA,.KaiB,
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silbi~ily ilJll( &fe::1!> iIrl. ,SlgJil<Ji~I'Ig ~.ays~U1!J~cl I:ly lacbgeuic or sn.roWil hoowollcs rulgl'it ufl'lJefli'e specific foou of ~,JiPC .2 dia.OOt(S,ilimlndiJlilg~la-Iniou8i1 di:aoo'lM,. and ,oociJe~m noop~ ~.in~kcd Ito

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KalA fc:r 225 li!'OC!fS giRd ~h@i!I

b~~~alph'!)sp'Jilgf(lfm ·di;swibmioo ~ Kait ,det~rnilil~ th!li:~!!b~ue!ilt d)!li!ali1ilt'CS. We I~rillialred Kaie e:nrki1edint l·KiliC bo~id dr:cle!ll) byinmbatimgl rylmes (9], Ccm'apiexes f,'Q;nnbetwooo dil,e Kill, lfl'rotc·iJ15 (.14). and the: mimi. \'(lproponlti();1flS orille: KaHJ.contaiillilO!J!; oolnpl,OJi;,(}S osci~law:(9', .15)1.
11];: 1II.1iiIQ1:i:rf ofpl~1~uyJ~dI Knl.c: OSCm[~G';!; wilt]1 01: dgdim I~OO (lI)" .HQ'!iMIJ'i.~, 'nhc Iroml ~!}'i,~C:~ f II'Jh.o~lo!}'l<lMgn C!Ut!lol: be !heOOlly dy-o ~1!!1l1iCi.'!1'iI>!I"ia~jb::' QOO1lmUll!'l,g n~ o$Cl~alo:r bei;ame 'il I~'~, d.1;(; ~:I'IC: value Inwicli; e.o"l.ch IDtll. m.cb l~illU::'lin !.I dii'erell~ diuooeli.o:n(j!Il(}UC8~~.iogdltl:liln:gdl£ !lu'iIDjoonlve ,dhy end d'cc:rrc:asi,l~d\urililg (11.e,~u'bjooA. '.

r'~I!I1IOOngl KffiA.lby imrnlllrnoi"redpJ'tltlrlil'l:Im',.We pr!~llIffid .KaiC emr1i:dhooinS-KtI~( (CI\pe!llsqu.ares) by inrub\!lting IJfilpho~horymatedl I<aie :wi:tt!h epitoplO'":I1li9geci IKG~ fa 18 hDIi!:r.5. wemDvhtg KalA;ollld ~~el!ll1Jt~owir~gi IKaiC to ilumd'epms" ph'GlI'Ylillief,oo .5.:5 hours. ln both Cil5iil1>, l~ri«l.I:lij,m ol.!icliIU1ltiioo~._1[e1Ilelil initiated by addi!llgl IKa~B"inrubatil1gf,clJ': 1,.5. hC!llIirrs;" tineIII reillltmdU!;IDI.g KaiA (_2·SI'.II'i~dMfit'S shQifi!·tt!~ I~~C pt!g:ip.li!gfQrm I(!~IMfib~Q!ilat!;h~ tiRll!l!g!f KalA re...:Jld'dmorn.

1m

... T,KslG
~

.1 Totalll."
3T~KaIC
:EH(laJjC
1 _

H:

"I
llil

I' ..

C) eel I
~. 1

I.

my.

~4C11'
2(11
1

~J ~I
"

MI

.I

1~,i\,ll 'm~gllt). Provious

m~~Ill!Uiel3J]ffillOO@]sl.1.ilI:VG

I~~loo bod] pl~pl~oryl<ttioosiles Ol,!l: (l!lIc~i(J!flllJJI¥ eqm~c~ U 6-24)<J1!1C1 ~lIVC pro~cI<l;ddiltona[ dytlOl.lniCill vW"l:ab!es ansi!lig ffOlTI Ipel'Si~ll OO!U~ fOnIutlii.omli dJru:vge.s (18, 20-14) OJ tmlg';~ivOO; ~lle.1crooompl~es (16, .1/);. we ~ypothe&2led thilt at:Mitiomll variables oOI!dd. 'be: fm,md by II¥xill1i'!lil~u['lg I!~elP~ll~iffillOr ~llillt~Dsirepl'I;Qsph(!l!}'~;).t:i(t!!~ Qf

01bol==~",=='==="",==='===",=~==<._dld "

0'

Tim~,I~I~)

10'

15,

~@o

·Ulll·

~=,==~~~~~e~·

Iflig'. 2~ Kaa.C 1~(lsp'limformkilrJMic;s

pho!>,phm}rlllait]mil lifl~~ b:l'al fuUli~

illl

dll!rim,g !!be cli!'Cacli;ua cy(:~c.

[(me

rylaoon at S43ltud 1"432 by SDS-~,~ooU)i,ll,unm Idnl!'.iltIJowoo.,·15 slimwilil. (0' Re.amm diagraDlil' fur thefOl!lir~tate iDlilOOid wlthr.m~Oofl(ief ~i.iil~G, gel~leamp1'nrcsis (S,Og•...\'.GE], (Fig. ~" A. 1lII:m, B) r and mass ~m.iftly (ttg, l~;). qu~fyil1g the: Iiluiaion alld 'U~en .a;dclJing Kati.B and KaiA. ItO h~i· afflitlM b-y Inlm presoooo of K:llIiB (fug. gil. fieStll fij!Mr" j1IOS5~bl~ mlhosphcrylalkulSlarllS:. lmp1ll00pbo. ~al~ OG';;i~IMrl;ll.~,II1.d~ "~~{l!]!!wltial_ed wilt! .<l. dat.... ~ d~bed w~1I by .. lira~ .~:u)(le~o:rK;;liC Iryl;J!~ed. (U':KaiC), p1~~phOfJla100~nb''''n 543 ~ ,fit!' v","n '1,.·KIl1p:n,.rymte~(!f~W 'Oft 'f4'::1" ,~" .,I' . 11..- lAI 'II ~.1.~~;...:)o '_',;M. "''I(m'n, ....jr, ~tC I~ al~~i!d. III l:iK<liC 'be7g!!~ f~l lIlC j:il~m· p:lmsp.11OIbrm. intefQOll",efS~ou (Fig, 2.q,DlOk'>ed and p11osri1~QrYlawdl(m ImliJl $4,3:1 md 1"432 (ST~ an d~~!<Ite O,'iII!5tIJllsc~t'Cl!I;o*:d b:), :~t~il1gJthese: ~h_ooe, 'Nh~ a If;,'aOillOJillu:!ltWilJ:cdw~Jl $'1), we ool:tctucilc KaiC). '[1Je oo:nQl;.';llImL1.{mof ~~ ~h.o~IDfoo)l hrgh~r..wels of' ~11:'.a1C bcWns&ll ~ile depl~oopliI!Jr:Y~" data (Fig, l,flg, S3" and tIlb'le~ a1iiQ11lpl~ (fig. 1(;]1 Ihl.'ll: l:aiA bQ1ibplXunmoo K.9!LC pi"!o.'>,Ph.om)'lau.ol1l, oSciim3l.e,~ Md~ a circadJa] f:iil:riod Ir!l. W:l)du, d:i1J~nt (a.oooooing to !I. byperlxin,c dCpllndOOlOO q:ua:ll tified ,.has!:S,creat~~g an ord~. patrelibl 0 1' jphO\i]ilQToumvestJgah;; jhe origins o:ft~ .wde:illd.p;aIJt£m ImI,(1&. :~) (J1), and :ill1hJl;bj~s iIDn'iI,il; d~ph~sphQo:f:KaK' phQ..'~ph.o±'olr.nsj \'1'll':d'GOOtiIil,~d1 'Um (lsc1J. r~nli'll.a'bl.'!~nce dl!u]rtg ooolil.~Jde; .MiI!Jl.tisil~ .~);)8ryl~~'Q.~si!~s ~~ Phoopt!ofo",]l~!l~fCQ!]'Vte'~i.Q!~ ~)hQ!jiti\ti.;:ltl Qt iKI1!rC .~ ~'iIiJ!~oodllhr~i!~kln, as "!'~orlH!O p~iaill~ctiOl\!l. \¥J:1en K,!liA :~ !tclx,w
!,~•.

\Yc nleasWL>d the ~b'!lil:l~peflOO!lce

or (:ill.ml"h:l-

fll'lear !iI1:00:el. (Flg~ .Zl]t issl1OM1. (B) AI;!,tJ;fICiliiI'U.lU$ deiphciSiPlhoryl,ilItllion o!~ KilI~C. PhQ!illillh,orylatHlll(;iflIiC was p,rei!plilIfENl! by~IiI,J!jl!lba~ionl:wiith KaiA" whidlii WIU thel1!l reril1lmmll byimmllm..o-' p!1lcipli1!aOOf!1 ,(28), ~iI!itiatlji!l1g' dep~~phOi~bii(l!,!~ A I~mt~.$q,ua:~.s rTt ~tJt]il lines) tD tlile' same 'r'OO["'S,taitl:! md8~With pltD!:p;t1o!,}!,Litiolll

~lriI he pUe5el1lbf: of t

KaiA. Po Leal~t~:flql!l![lre5 {!liolid iit

pilrtial re:actiolilS<.

(A~ Kaie

~~"nml

~rnl nn,dadQ!ls. at ,eM~l'1i:rS4:n

I~)'dlnl!icity (7, 8), (fig, S:.I),

go

~in'!ei\lCi)~e ih~ {)scg[l..oorn; as T4~2m.1O!!8'I~ v.~tl~ U.iKrnC, r;'J:;;,<)!C .,!;QQtIIH1UW :Uh~~IDllQ'''w QWurr;mlll~ s<!.:lne

,(heprodl:mmi~Ul!ilOOef disl'inclp]lO;.'>plmfofrl'i1S at diltmrenlp:llltns in~ aycl&---"f:.KaiC:: dlurillg dl.'!': Ilh.o\S,rJ:H]I~ylru~iO:[I. ·~~;;mds.:KaiC durillig lire d~llQ~hLl)i'laili.Qll plga! _ rug~ts Ibwl idl~ .~~

[);horoml distribll.!lian {Of a call fOf:ndiO!l ti.gh:Uy Ih&ed 1:0 Ole ~hGS~~O[yb:llimi~} ilia)" dcte:nli!i1e i~he'iJhl!lSe' the {)ScUlal'Or.lf iih.is is Re,it SI;~lU:ld, sllIgge&ts liim1!3"KaiCils: r,nrodillood from 'S1'~K!liC of 'by d~h.{i~!ll.OiYJafiom. of T412. Ndd'r::iif l!1~e pat:. ~PO!lliill:i:le Ill! .~fy 'dlc:tni~ial~!I6~ Iby ~~iI'I,g Kale wit~' li1I~ !!I.~31il P~lMp~~Qirilrmdi!>ld~ !em. of (k;~hfiS,~lt{irylat~oll. ilOi' ~.ts IdiUnicl! is

by S,1j:KalC" and evenMl.mlly by S~K<li~C(Wlg. 2:A), \Vh.el~liliigh~y~aosp!lrnybl:OO. :lKaiC is tHClilhatoo. ~kHle, ]~ '3.UlooeplKt\ip.booy!.a;h1:S., and the COIlOOI~~ionq af"f;.Kai.(;andSKt{aiC d~eaYllxmo. Iollic."IU)' (Fig; .2D), C'o:nOOjniiant with tim .dec,,1:Y o:fSl~K.at!,'C, i~ablin~&J'Kle ·of S-Kaitc Im~ilet'il~ O lnereases bcroreeventuail!y decaY~I~g"whkh

ihel1J.se~'ii"es,. oornsJs.wl~lw~l:h.~te idei1llbat ihese.1lJie keysil.oW' d}'WI8.11il11iCl:~~procc.g~ncill::rl.yingdle u o..:'iclHru.o:u. CO]Tlilli:nlmgdle: plosp'klfum,l ~runrcsaM::tvGd
t!ile

imI.d'l~ pmDii!ll

~~i'On,,'l

{Fig ..l,A. andl B) yit!l~&Inlle;

s<!;!l'iC'q~li!t.Jiive: p!lllem QfiPh¢~1lio.roo~abU'ndlu\ice

o'bservedin lillie run ,oscil1!at~1lg .~H(!tl!, su§SEir.Jg

l.iitlrl. eadb. ,c}de of the OSC~hlllu.ilii:mn~, of" <), p:OO~l«)'~locmp-lm;c ofi~bl lKaiiA oo1lvuylbf.. 1.(1\""('(('by Zli d~~~1niY.I.:Pt~CIi1. 'pl18fle ,dmj~ whiclr.

810

REPORTS
{Wi

Q 'till: 6® ~

.£:: SO-

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,fit

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~ #-' ~~ .
2nl1

D __ pW~~~~~~~~~F91
'il~

a~
~!().

Oi!WI
~

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il S~
8"<t®
,;=; ~

6®

f.

Z[l

sa .. 1®

~ 2~

poo'~I~~b,;g~ Jt~l;l'!e. To :ru~Q1i!tih~ "Ire!'!~i"'-e c~Jl~l~knU~ it .~i!'!e ~~vi~ '~K~C b K;il_ll" (21, l:1)-m.llller InI~"l tlilC acti!iiro;y of KfliA i~lf':_ !mil vJ:wrnin a clrcadi~~ cyc~. ~ marmre<h'lilll' 00fi}. OClUltroItt;i1l ofKaiA ~l.~iC miidrl:1b ofdtc dcph'n:TI.1ll!tyl,. a6alil jl'Eia~ {fig" 311B).llte p:lilosphQ:D'}'~.il!liaiil~t;iV~~ of K~~C:i~1.\m~dJlcatel.>,imi~;;;oo. i"d!!~ti[i!g In!lal K~~C~<K!.!lot ~neiR~~sili ve ItOI ~~. rnadivo'!!ioo ·ofKaiLA reqw;~KalB, as Ilomei!,. laIIm'll!lOo!l:)UJr' in :lit!> a~llre (9)1 (Hf,l. 2A). Since jlroil'ioos stOO!i£i>I~::¥WshOW1l!'lI!~l KaiiA.·.KhlB.JCaiC COi1I:'iplrn.'lEi!'.! fOnnl duriilgll:m cl.odo:.mactim:'i Md. Ithat KaiB pm;__. ......'iII¥>.lalM. KaiC tQ~ c . _ •• 'rmntialniT-dho 'L_",,,._~_. 'Y'I._~ w,~'OO1'!ied!~!'OO.l'h1Jt ii[lartlvliian .orlC!liA amdl!l':lK¢ j~l~ilart!C»l of ij'le depJ!ospIlal)'llolliiOl:! phase OOOll!!'S Ill!t:n~~ a physica!inl1Jr.:!!::lilonbdween a spooi5e poo.ro:fOOitl of KEilCslld. :KaiA amI. KaiB. V!b foonddilal 1I,~WI1lt}tio:U1 of T<aiC'am:l. K:iliA. {'on].. pl(li(oo. wilth. KaiI3 clO$C(lylllliows Ilille a!:J,l.lm:laJllooor S-K<I1C (Fig. 3Q,\M\lich 81L1~e.<l'iUliat$·K.,'lICmedialcs ,S! ~pi\l'er~htCk 'loop 1~'!!!'Wghi!,!ar;H'I'11!lioo of hi!\.. v~i!!KaiB. Beca.!se S4.31!!!u;l T432 am
~}I

1(1

KariS 5Ii!,PPJf@S5es:KaiA artivity hi an S·KiK defell~'ent marmer. (A) Gloooll KaIU!!ililrnmy vanes l duu:iiingi me' drC<ld1ia:ncyrle. ,[)epliu'l1l:lidi1D~tea; ~i%·KaiC (hn:ialJ'lgoos,. rin:lei.s:, diamood,s) wa~,ad'dl2dat 10% !l)f th@'ti~n~!l:~~gtTIoo of u!'!t!g~e~, I(,g~.c '~(lYiQresJlgJtth~ ijJi'!dlcat~dti!'ll~ {B~ Pl:!@sphO!l~ltio!il. g!CIMI,y i~ Iraphily Irl@SWlr,m by the, ~dltrlilIlI'IJ o~iI,~f()1!i 19~~!'i IOf KaiA, dli1r'i:Jigt!1@ ,rnepti05pim:JfyI.QtioIil, p~e 'llrialilgl~~, whicln ~ontinllle!i'~1iI HI cDJiltmlt withoot el!ices.s KalA, (5I1;IlI,uE1if (() lKa~,Bil'l~r,am(m Witln; I<ilK illl1d KalA, 5~W5 with iu~ abllllildan:oe- air $·Ka,iC.Th~ righ,t ,;:I~niS' shoJi'llS th~ IliOfmatli1ledl ilImOIJl1ilb: lof Kaii( and KalA that IiIG~!mmuniJ,nedpitamm1lil KaiB·iFLAG lI1J!iilliIl OISCmatinQ Ir'ffij"moirl; tille' l.eft ~ili sliiowsfhe [otri~Qn:riin;£i IphoSlphoID.mlili1l diswimrrrioo. I~)D) KaiS dol11'S,IllIat ,af'red:: Iphmphor)l1atiollll 1I1l1tij[ 5·Kai(, Is glbujildrurrt. Il!l!phosplilorylgtoo ~~C wa5ifl:ouba'~~d w1I! K:!!iA. ~fl:d KaliS, WQj\) i"tr.odyc~ 'in1:c iIih~ ~cticn art various, time poil~ ('lx'iatl!lll@~, dr,r.lres, diaIlflOnt[iS) !llndl COOliPtJif@~ tea C:Olmf~l. wiltiQutlidd:ecI !!:aiiS: 1~$quarB5t Pie' ,dham shol;\llilil,~ lKail( phDsp;liIoforml diS'lrij~u:tiiOn at th:.etiln1e af l(aiB a.ddri1iolll. IF'ig.3.

Inll:i,e;::l MDh1if1"1D~e K:aiC flii.gomcr (2i5).O]~speciffi.c l preference of Killin, for S-Kale SU~I!; InI~IU cliilIl'Iig@S til. 'Kille [pIiOSPliOrylaJliO:ll lli'DfI)' be C!l.oS(~y tim OCI l~lfQlmmliQl'lailclmllg,(ilS go'I:'ISfiJ. by iKaJiR 10 {

i.~late Om ~fftc~ofrl~~l!Of)'hUrlQrl.a1.'~I] ~ro·~ KaiBof:!~cdiatoo fulXIbaCk" '?Ire strJd~oo ;sif!isJe-.si~ I1m1Pho!f!l~Ol:)4all1!li)Ie K<liC m!l!l<Il'r.s OIIil:dfouad iIJ!aI KalB im~lSpref.crelt~iaJ!y md~,~helwll!lilltrti'bo&p:b.ooyloo:ah]conly em 84.31 (1i~ S~ and alse ped'" m!(l¥ltiruly m:hibill;il&p:b~hJJtYIl"ltl.QJ:'I (!ig. 81Al 1b fun!l~rin"'~~OO: tillie '1!1'liJJlu,gofKiliB FIiIIl,o.

En

tiGllj "!.'o'C imllfOdoctlclJ il~ ml)~.K.tiA~Ki!!lC~C1ion

!II.

vOIri!()us[pOin~ (Fig. 3D) ..AJ:idinll!J K:1iB Ci!!ri}!in inl~ reacrio!'!, whem S«ruc le>reGs .. ~ .1!Jw. dUes '~l lodrn:;8i~y jJ1(I~~.c dev:latkOn Em tllc !:<aiA=KaiC OOI;Utml ~ll1il g.·KalC' ~~fI.:~Ii'COOII.m -~ Wh
aloomdruloo.. [j.~ro~lI:mt"in~I!ICln(m S-«aiC lm<el.,aIDe <1~qdly hlp ofKalIti,
i\\,~ll'll1l.

(:-~ 5%}

Il'<lpi(ij~y

k •.' "$\=
.• 'Ii:( ~" ~ -

k~ .
''X'(

+
-

,1It<i!ed, ilw simUocl.tylXll'\\Ve!,'l!l the dC,~I'KlSphOl)!'I.~ 3dm~,pan:iln~:Cat~ by 2ddli:nlgKa!iB wllO\lfl. $-.KaiC 1~1s are h~ mid. that .• tduoodi by retml'J\1iIIl'IgKalA (~ S~) d,Ciil'!l.gwt~rf~~ IUI;I: ~jmg .Kai13h:'l 'nI~ p~.\~e 'of~!.I!b;nallM:i:aI S.JKaiC L5 e~l.!hraiUetJl ~o

h'!d~ d:eplmphOfylau'O!!!.HeiOCie. S·~iC pl~ys .. s,pootal role :tr!P~101]IDiiliL~gIm'!l:tivaliO!l ·of K<ci/!...

K 112+ ,A,(:5)

k"~:y A(S)

!:eI.l1im!.i!!g~A

A{S,) = ma!X H~.I [11i(a,iA] - 2S,} 4. A mOOIel fo.r d:r(i1Idr~lr1I mdtlMi~n drlvenb¥ ml!ll~iSlire Kale p~o:spmoIi)i'L.moilil. (A) l<aiiA oillctMty i3llter,s the fir5t·on:l)er rare c;OO5i1!aJl'ltli, r'im~rtomr€'r~)iotl'l 'oil' lKaliCphulIphofimlm!'l. I.:il'lesemlillili!lHmgl flrom m Ki'liA ~Vi!d~~gli!ilIil!f!.a!fiIi'QW~~ad (bla~k) Ol~b,a,f'(gfilly:j, !1ildkat~stim~lati~n 9~ f~~'rl~sg(li"',.fl~pecti\f,ely. ,gfthil! ~[a IIIsi,tiioiiirow.alm tile 1m dicat100 f,orm ,of IK~iC. We SnOw Or1:~yli,@ dtllmilii'a lilt l!:Hili!dS (~eE tilIli1te :52: a,liid rig. :5-:K<iiC ~lI1aGtrNat:es: lKai'A lll'al KaiB. fine' ililiterljOlW'er~OIIil rd!te.sfirlGm iphlil~phofmll1l:XID Y, k~, dl~lend hYP~fbQlh::a~~y <01'1 t~~IIl:Q!ii(!~!iltraitJ1'o!ilI,4 (S) ,of gaiv~ Karitll~Oilil'Ol'liUl!f'S w;hi(h llliltorJil d~pef1jds '011 .• S:·l(ii(~~ r'oU:[lllIiitsinlilibit.ory ,iI(~,1rity. Sell,IiIiI,~supporting on LiJlilIE!!mxtfm the' (om pliete !MjU'iltiens o;¥the dYiilarnkal modeL ~B~I NllllImeri,(al[ i.mltegra~ol'l of tln,e llililociel~.rleptro!l!IllJ:CE~5 1!:i'liiLilIdiil! n ollcillartiO.1I10f IKaii( l~hQ's,h,O'~gti 1)11.
f'lg.

'It deWrmin.e wl\\l!Jt!c.fi'o1l!fl.l!!Klc~l'lJ1.din£l ()if' tIilc p:hoop:h.oRi{ltl 1r;iIIClics Q,nd. fwclhID.(:k me\:h9F nim
C.q!liH~IUfll1ln!aln.V{;~~1" OOOQ1!11nt

for lire cireadialll.

suo.

o.:~ci[~atioDl o:fKai.C' p'&lospbOtyl!a.tio~, Wll:; creallMJ. a sl1l:1p1e: 1:rulII~1Lm'la:nica:1mooe:1 (fig. 4Aandl fig. S6A) cm~"lfl'!ii!1loo byQ!.l!!" ~·pt:;rinle!fl:;;i~ !f!~~'"' 1TI:~~~'5."fhe :key ..~mpik':~" or lnil:!s !lnin!n!i!1 InOOe;l are· (1) Iilie OOIL.centmh.OI1.s {lfUleJ ~,~r:ee

pboopfuOliYi3~OO.SPQC'ics am the only s~ow d¥tnarlj.. inal ",rniabl~; (H) Illil(l wl.e:rooJ1.Yers111D);i> ~~'Vcell.
pilosp.1iIQ.mnlls !lre filf$~-ofd:er I:'lMLcti(H:b.~ withtJJ~ilS {rn.lllliil $2)1 thrut d~~f~d! :h~~tt~TI.t:y 'OJ!Id.t~

KaiAis.il]'(';""live. l"Gtk.'sl dlisid!ea, whitoh lias beel~ 1J~p:i'CVimjsly [~~.,. {9J]~\witnrodllC~ a ~mctl!BmI!ily of ~il~L'J.ifal~dL"'pI~j}_SjJI~a.oo:

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REPORTS
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dllO: l!.cey Il:IGillileut> of d~Q;~1 ViLro ()\1c!I!liittlf:; MOC!iryitg Ith{! !'I'fIOd~ LO~"P~.citly lfifl';M 'd¥li lb· -'~·r -·C· .OOHi!~"C'~_~".._,~ lik..l ... ro---...-JI-. ~ -"n) __ !HiUU;XIII 0_.. K:riiAJ( at .__ ,.

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!IJ.--dll!cti\1'C: l!nd~a!ldi!!£ ·(lf~~c VaftO'llS ~ecl!l: ef for :r,rtm!o(i',g KaiC pb:iSpilazy1atio!~ d1.ecl\:iC. e!ilpecially ~H!il!if !he (lore Ka;i o$ci~" ( :~~. OIISi5.b3]I. w1!h die ob._~;'\1ttBo:n 'UlOlt he c oscilllattQlSW IBtll).I"~~~~sil:i,,'C Ito dtcIDIDlI (\(l11.~ lai~Q('p~ntecl: IIlmn.,":----,sholllkl,enable us to lInder~ !>Dfi1I1IG IlhlC ~lTems of rnndm:w, IlllCruati{u~sand Cnfilllra1b:i!I nfK.aiprolnlllil (9) (s~pat1l'lg; unllo(; t(!X( v8riaJbil~~n,v.romn~lDlS. Die Syrtttdi.{lCtxt:1tS elook: 3JtdRg. SS~ 1I]~ fl)~btVl'~~ piLUIJmof 19rc Qnsi~ ,of Slabl~ :pr«v~d~ "r:lidl;all~l ~S~~:ml!ba' un~.!)[Slandin~ @!'Icilhti:(lf'l8 ~.rm!!~~m~ S6.A), SI.mi~rmm d~e how eells ~!lM~YOU1~tUi""e func(~onsi!!LWli~~ 'Il!!JI~1.o~-~]altl:.d:i<!<lle. alA p:!1OI'l';~ ~!l{l8phafJl~ vmi~~le intr.1.~a!lde.'(u'l)cel~!Jb!l'e!wiron!~~I:S. K ationllli9tis kmm.rnny :1iI.wr:o:!. at Tlll32~ ~~l}UIl 1iI!!$Il!!'e!!C!e! .a!!!d N!!!tt!! I;i!h_O>llhn-ty~ati(lnm S43~. j?rt:MiLces, Snil.ic. ST~ L S- L H!a ImI!r, :5- ~.illll!la., S. ~" IGIr, ..tImu. ili'tv.. (tUo.>v, Kille ·eaJl. ~!Y '!lii..~ c1L!@liIOs!ilOl}I~tionifT432 I~O o lJ:Itit. 11. 21S {Z,OOill" 2. II..fMl~tI.,~t.NM1lJlma 11. KtimM, I!I. Imm~l~ ~dr!l1{1'!' ~fOdn(2 SJealC, blill! S-KaIlC aoClilllliil:latk>nis :shw 307. 2~1 {2:00iS.~. ~~ KalA ~~ il'\l~~'biti)wt~l!l!l~,l'OC)'bliil!~ ..

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and p:oomCl~~I~Wim of S.,KriiC lO 81-::' K!1lG l1ulS, So:KaiC ~_evc1s~I1<!!in :bw Imm <l: sio. S'tlialW iIK'O~. of ST·OCaJiChili fnn~lCd.~.l(l;l. s;KaiC' .~ewls do mire, .1<:aiA oo~vilyis m:llICOO\ Ipmln.lOlmg d~lOSp111ryJ.ath:n orST-KaiC m1d.dillil':~ ~g ~IIO rapidil)' d'ccay ~I'ilb S~iC UI,Il. S-KaiC :oc:cele~~~ ilS: 0'I'I.'IifI prOO!!!ct~li (&om ST;.J(.uC), lIAl~h ca~ iis coooof!!ntim to' Q\~~OOl iI~IXI1!:!1. at wille!! KiIiA .isOOlnPlk.iely~mCllwar!ed:. ihi.s ()li.IIC~t
ya.olds a~ir of S,KaK:: d:k'l:~ m:ennilS ,('lXIf:I1<kd imoot~va~iOlfl of Kfllm. even as: S·K<tiC'(lo.mccn:~Jl<lli. 1~1mt'ld~ IiliIrooghdepl:rosp1:mry~atktlb..11l tiro a~n.c~ of KalA activiLy. T~!KatC(l!1!d ST~[[(@iC' Il;li)d~d.c~!m:piJQry~. ~d S-~Iliroo de.,-

3. M., N!~h~ifI'I,!j ~.,~fI1i'I()2 ..!l!' 301tH~ t200,o;)l. '¢' Ii. M.lllIii ~. !?~.,['UJ( • .N.rrfiL 1IlL1l15([ 0.5.11. 99, 1.7203
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S.T. Ni~mW'!lki. H..11~\\iIii<lk~M.I~~'uf:il. T. t'.i!iniJu.. Proc;NI'I!J. Sup',pil,rtingl Olil'hll ,Malterlal. ;'!Wilt Xli. U.SIA. 97, <l~ ~ {i!;QiJO}, ~. 'It .~u.r; lW!!<ri, C. fI, ~h!i!O'll, ~'J ~;!.i!n\l ~~,oogt .WIWi'. ~ieno::.eilfl.ilg!.grojuMomtel!.Jtullllj[MIl5!j!6!lIOCl Miil~ffi,~l~<Il1Id~tl1od~, l 1_ T., Hn!.i1t1l:ak:i ~ m" Pi<G!'_ .Uirll,. ,,.l,iItJ"til .:M'.l (ilSA.l~i, llli'2,1 $O~'T,m (~~!lig;. S;llJ()~U 9•. 1(•. :W ,~. ot.. ,Ptt,;t. !tlfllAalo!l',.Sif lJ5A l!~:n.H9.B (2tOO!l",' nbtes 51 ~~ S:2 9. 1'1. K~!)I!)'llgllil ~ 01~ Mot ((:It ;~3~ 1.6,1(2000). liI'i!I',ere!ilC~ ~.o. s. 't'e, ~ V,iI):onak.i~, 1. J!:. Ill!I1f>[!ef. A. c. 1J~~q. II. c. S;m~t~m."t.Bioi. ,(JjStr,J. 2:19, 2~5n t2:004t U. 1-1, ~\'!~~~il r, ~i;iOO!~ki'.'1'. !!iii~:f~!g, M. Ui!~~j!mo<!. 31 fuil" _jl'QI07;~W:!M~dl ,11, :~p~mW~ .2:007 V. !!'it1in!fQ,. Pf(j(. ~if. Ai@d. ~n, {J.sJl.. ~6I. ~~ 73$ (~,OOl). i'~~~i~tJe!:llilIil\i!! ·~O~~.I)~r ,:OOl; ! lL 5_ 8,_ \I'l'illidn:i~, I.II.:tikOIiaK1S,>, S_ €!:Jll!!f!rn. A. (. lUl'i'amg_. :HI, U261!:riecfl~e_n.t~,911 ~_ 1ifoliL Ar!Ul, 50::,( U:~A. !Ji9, 1.~d~1 (2002). ~i1[~iJiI~ mrk, illl~~ma~d~hen cHtllI9 [hh P"IiPg w

fh.osphocyl<!l_e5 ~~ s)owty-beiJolll€8ihe do:!'l~~ ~mM.- OOllla!Lnlil,g liliiO~rol.yl~&oo. srecies. :EMelill1ta1ly cllt)Ugh S-:£<aiCdCp:oo.s:pbmy1at\'S for KaiA ,ac.tM~y to I!1:llDlI!, and!'dm:c~l.ebcgiM a1~l,I •.
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~~.lbe ~bil~ loderiv-e !Node! 'para:!~~'('''J5 d~fe~Uy fOO!11 01!!f oexjperi!l!eHf!iI&tl~ Q1Jf ~~el~gnoi!leS scm)!; k!m'!'Vl~mQcl~(;l'Jnl!calIJl\)poertl~-~of lhc Kaj. ~:I'CItl:;lnS,nldl IlootrnO]sotUieu:s ti.nt(ld;1Cm~~ con,~ sinn'liS.Kaie' ex:l~ ·fIS a hex8iluar and! \!,lUi have rnl!l.lglootedl~ll~:i:ble efFects drlatdCpc:ru:I.on.liliIe start~ ot ihe Gfilni.ffi :h~);iilmer; F!IDllilt:(, m(llWmer ~l'i;ch<!!:1:g.e ~tweo.~ 11e;i;:.u~li~(9) is: not ·~~pHdH.Y i~c'u.dC>d,<li~d1·~~· ~me tI'!.ai,irnh~Dlt1m~ 1K;~~

Disentanlglinlgl 'G,e'nelic V,Bria,tii,on flor Res,istan'C8 and 'To,II'B'ra,Dlc8 ,to Inlacliii'D'US Dli'se~,aS8:S,liin A.nimailis
Lars Rabe:rg!,:Ji,~~ D.er.-ek Sili!i\.ltAliiJdJ!iE!'W IF, Re!ad~t !foiStS '!lJilrl ill l~ril:1t$1e: employ 1M'O d:iffer,e;m ~filite;QIes ro defernd 1tifl1rls.e1.\;Ie$aQaill&tporn~ res;isttllfl~li! arid'tolerne. AfIma~s;typically eJ:jhl'~iI: mm:t:dera1J1e Slefle:tlk variatiOI1l W'l)rresistJ1li1ce (the: am~tyro Umft pIiIlmSite 1~lr.I'IJ.HG~r~ little· ns.l~nMiI.aiDootMe1IIner."IIiIi'ml~C;i!l11 emhre tdlier.mrn (!he abi~l¥ t1l ~imi1! tilie· d\;mnag2 IUllllsedi by .. 'gl!venl 1~i!lrM1fto lruii'dend. IU,!).,.g rodenm: lrillialam 'hil' ma'OIIaml)!' ,!11IIc:e i1l~" IrillIOdel ·~alil~ 5tatislkal !framework d.e~~O;Iled mtant-]pmliiogenl Ibi~iSIr:s,. 'M. denrntralied by 'Qed ~riaf!Ol1r~m tdl!eli'afl~f ~. ~!1Ir,oo bt lie ~ttlli'ihid'l ,j;lin~mii1!l"'liid:weig:irIt lo~ ilii(~di withinLi~S"in.g .Pflirn~b"'Jden'. ,M.Ofe~~r. resl~i!1!:1: anciWlefilllilu: n~e: IIfl~alhr'ely gelfltlh:al[lI'~OIi~dl1ihese re~llts m.9au~M;a!liIifll;lat, tlke' p~aJnrts, fillil !l!V·tlil:lR cOil!~~'-aM:y di~nt two tyl~S of dewlfl5e, ,afinidlflg, thM hIlS mpottfllilt rmp~,aticm, merUn~ Il!Inder:s.tandril1QI,of the~pic:fmfni.olvgy ,m~evdlumll a,v Tlifem:ot!l,s, m~51~

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812

REPORTS
If.Hl.!~i~s.w:!l~~ ~Q~tNrul!.1e @!; ~5-.~~<Y!~ does ~Ii!ei!'~~\'e i in!~nw .,,¥iI:l !imv'e HlmMw<i1 QOO~ sequcl'l(les for llIiIeecology ml,d ,ev()J.u~()f1 of.IM)st~ fmJSi~ intllllclitmts· (2, S-~ ..1l11.~~ di$liua1ofl btt!Wl.'m~. ~ ~ ro~erruiID(!1~8.'allm.cl\dlocmidcmb.fe iW,'(1iill.(iifLiill.~cllt~ ofth~ ~\IOh,lliO'Jfi o~~1umI1 ~f)/):\~ . i,tgainsl pt.;l51!~::li!ldlbe.uVQ~ (1, 6, 8)" [!lIU~is.~ Ithee!'l'ierging~~ is th1!ilP~MISget~ly e4lbit gii."<!~ic~aria/~iOllrorooU~ ~sta!'loea:llld i!o1ernrice (1, 6, 9• .10).

m@60~ fQfIQ1~~ 'y-e~rf~~n ~perim~l] v.4ihfive dil'~ ~~ n)IJ~ si_fllhilS f,I,Mice (2.. ?i.'t.'1"l:~I[feo~~. willl' one oif (lee ·clilifuliiOOt F!: dwiJ(ll,Jt cl~ or I~~ U'IJliimifOOOO.~la fumy f£L'iIDnai dmigjl. 1l1C ex,mIWCl.'Il wa.olpctfo:nnocl.ind~, e:q1Gril1lCil' tal b!~ll ,s~~ Iml. bl'iII¢, A~~ViU.tb.i!lllil.'1.ti 1.~'illaJtija,

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iWm !'J~ma .~ ,Ule1WOii.P. d~b~jl<li aL-ro cali!.."C8 \','i,;,'iigh1.loss it! 11I~:Ce. The dt..~ (If 1iI.>d. bIDod. c:cl~ (ROC:) kiSS: ;Md! 'WCl{iht 10SlI .ili> ool"l'cl!i~ wiinh. :~nfoo. Vlhm~l QOil1CS to aJfIiil:fiiii~ ~U:II['1Grom, studies Iiiinunli1191y ,rud ~redl'cts n»i1:aljty {2:~') To .~~.[(j" ~mw dll:iMili!l~gmliCtic V'.maUOOl. :for ii'CSiisl2nre, 'wriatLcm .~~oolaOCle,\V(i Ihere[trc usodi miniiWllliJl. wl~~ ~~'I;OO: E:s·lY!PiicaU.y I~!!!~'d ~d~i!trv~ RBe d~!SilYt1!~ Wltil:iin~UIln v.~lSh~d:urin-s 1~1.¢1'I'. (iifp.u,a~oowro~~ (/l-l4). HO'W~!; lime is lm.Q<;V',~ klior!ai)!w~~ ofd~~~erimy(atl<l!~~Om to liI~I~lIedWf aninlats I'll.'!:)' <lisa ~lJW £l(lll~licvoc>. 1!OSI.fi~oos.s u..~i!l!·!he ~~!I~~ ~itC'l~jJIiI'e~Spe::i'bicri~ly? 'i.. '1ItiOOl ltb:ifol~;.;ocr.\ Vt'lt 'tos~hcr~ i~~oe m. lo~.~ we (esloo \7lihelllCf the !llo,pe5 oif dre rel<!!liol'ls ~" ~lOil: !!rn~.tc 1\'00 QOIlfl,prnDU of aruip!!l41mgenl defoose ltihat drt:c;,m.llim; d~!';(1l,l.'1e sevmly. SUggilSm.vc ~d'o.\refurl~:oIJ~K]IC:~,l, _limit! roJ:r:I(S ~~lnn] :I]Iwy a (lfot ~Ib."&~~. $.Ii'i{llt~.ii,; 11U~Jobiill d~;&' il1 ~ll11n~: !llc1a~proWCl~.~!~ m![dl\f~]8
h~.ero· Q·r l\'OnI:O~y~(JlI!,slbrU~LS [~'HllI~hon do 1:kJ1~lSiVC:IOO'tY il1illoctl<m~nl~lmul.'S OfPlasnlDdJml,ijaleiprnml iI1ii311~~.dividilllJ; mt :arc·h.m:lll1li!Y~ d gQUfl b ItlOOwiMl~ b:lt d~~~olf' am'llt'l:ba at
1!ID!a!!<!1I'e

[8

O.il

I~n@ilii f![lmO:ll ~['jl.@imlli@sis d:ti1l.lilt'lillhoo. 111c;n_':by ~mu.ci!lg:~lO!tl!~l}I ri{ln~ !l1!lil~a (J5) ..1l1ll!S, it ~~]iL"
(l! ;. !~'lClni<laffro1lsLO~iOl!I!ce ~

In.wo CQll1potlCillS of dsfuMC m. ::Iny ::lIJ,'limiRI. bosrl;lill'3S:imc: sys~£I1l1" ~nll~pllarll til~l!lJi'e,b!~c¢is !:h~a!ly ddi~ P~!<:!,""ebu!7den ~ ks~oflJJ~Iiil!fJ¢..ss.<l!~iI1SI ~iI~Ol'I mWl~~y fiig.lIl. Sdile!ililiJlh: fi~,n.e s!iowin:g reamnllil n~ Q·f (1. 1(J, 1.7). ~!fI Qlher oo1*, ilielcilblirllOO of 01.1:l!')S( ·two htJS!tg)enooypes (Fed !(If Ifue UIile1 1,00 dris~se :g.el\'Jlweis irs reoothll nean to, :~JooliDn :intcrlsil}t A ~rity imr1M!'iil rHl'Ige'o~ i1!f~rlii:ooilill:t!rnltil'es illilinr Itd1'flll~ga~tct:ypeiis OIU"~l.whiclll dlsca,<;c S'l\~rity is ,dtlitdu.a[ I~ (d~~ (Po) ~ ,equa.llyiliDleraurt ~U!0e' rn'C'latt'o'Oly lmafioowd·b,y i:OOIlt'2l<tlnlgp8b::if$~ hun:loo,. types; djflii~qh fm~i!I(~; here, the ~1 g~OOV!il '~l,illl.l'lliClildl£ !Ill~ of iii t~ l:oih"WIII111.!J'llOlype ,00.. hilll> I.bwer parasite, Iblllfiderns (is m~ re!li!illlllllrl') .and d~~ ~~nil( :", ~;~ idl: as ~·~:w.:. ~b·I!I'&n.~ ~\' g_",1'1'. _ . _e.'l _~ _y __~~ ~~_'I ._~:sse [if iJ::, ~_ '1ti!1!!l!lby rmililt;Ji~ Qj l1igh!llf' h!!l~1lh ~,taW5 when Ifd1C~likm !lO!TI!Slif&freretll i~~!l{t~ { 'l,i'~ ilI~l. (I) 'mm 'eqt!'idly resi~lilt g~o"es '[same (~!a115";ifdcla.lW ~ ill. !l~MiC<:l1 i~lUll"OCiruO!l,t':eltil,lOOtl host awraQ!! paw'te bumlen}. but 1~f1ethe· red geoo~ gen((yp:: :tnttldion h:l!:c:nsh)!'~dl'OOt!IOOreis ~IICU:U 'i!: lessml.er:ant ~lili~l3:t1h,dedline:s ~rwith.IJiI(re;tS,ifilg 'i!'anaocm tor k:l~etaroC.. We I~'i!& bnilfOMlM ~s .apparaS<itebt!rn'elilt (() GmD~es, diIHer In bd tOller" I;l~fh 1.0 d:cfu~lmg ~ i.tocarlJlring .galt\lOC v.ariali(lnin. .afire and ImsiiSl:<Ll1lffi,; I~Nl',.the mOf"!l tolerant g;mois It{)ilei:'am~(l ]lnin I~m plaml nrotcli~ure3i.'ld. a~1ffidl it I[j;)a typE. [h1.l,hi~ Ie~ l~istallt5C1 th~t b!otI1lg~o~ ~.l"'brill m~~ !'i~LIQ".l (l:t(r..';'1"odii~m,1~'Q.~«li .il~ ,~1 l!P h~gl •.00 a.'!iW'~~. t~~_iiI1E: heiJ,~lhSl:ailiJ~ ~Ol.I~]I!:a'rn:y n~ce) to g.!wes!igale wh.eU~l.'fi!!!;1lma~ whenl irnf"eded ,~mHb~ gBOOVes: diffi~ i:ri1 lil.eil:ifrl2r f,~tbii'lG'i (sal!il'le~rage IPIi!~s1te bocd~ iiiOj" tll" ~ooI!; iIlUY showge!~elJic ya_rialikmlOr t~lero.JlOC:ailJ1Cil

P..fll'l'dp'lJ1wll. So .rar as ·wc are !I~', iI!l(l study has yel ftm:mIlLY~11IaingM g€l10~icvlmaoon ilD.lIDw

~w l'!ot!ieSL~JXlto

Peak f811!dsll.elllensity (1WJ!!Lb::lIot~

Ft1Jl, ~.•V>ClliillwflWftdeltlnOOallm!i!Q rnoo~stta~n;.

I'Al

M.illIimillil1 RBI( ,dilil'lS!iy l~lbg{r.ml5fmmedlV'er:S!ll"

(1m

p~k para~ oo~I!!!IOO5i\'l~gifll ><I~a~~ '~l'!~i .Foii,l:l.7 ~ 6.08 • .P' ~(M)OSl2:; pa~ite· C1mslty. ~tt? ,~ 1]3,.3,. P <: 0.0001; 1!illllmE1 !i1raifl: '''~:l!.1.7 ::: 0.201 .P= 1194,; ami experililile!li!Iiat b'lo.:k: x'Z.:: .21.1, r« o.omn. InitEal !RiC dlemity ftm .;:;:,0.80,P ::::::' 0.371\ the q~d.fajk ~mms.l[plil~5ful m~~.:_li.m _=. 0.. 6, :P.~ 7 O.3ll• wall x IP~U_ de~ity .F~ru'" ~33, p '" . 0.S6L illi1d1the' 'ifl!ttif.!rtil!c;tiof! be1weWl blo!:.k snd
slrailill (:P >0..25]1 wwe' mJl:!>ignfficalill: end .~

l.usl.sI<lWean.d tolernn.ce .~ \Wtfekuw tn(a. .R cJmooudi iswidn~ymedloo :8ii~ QUUlInlln. imalruia O~,J9.).P.I'~l,dous srudJ:OOI~v.e :!lltlO\vn d'tat Inhere iSic~id'elahll£l, v;'ll]alnoll a11K)1lg li'D:Y1l.IJl!'l.suai~ t' .'. . . .~r. .. . .. . _. .:1 1.J· \,1,e.. ~!leij.c Y.m~~~.\i'_lJ_lfres~iM!~ Ib p:. C1ffi~~f(fd wh~ber (2Q-2.n. 10 inv~!~ wh~er~~1Ie

is <l1oo ge~tk\:

'~rm (Silm:e~) .. IlmSlEalll,tiile gerBil( differ·eoce ill lileatlilil m.mSi5 dll!! to i! diffuoonooin ililwrcept . SQ.!lilita1t !!he. ,dif{erelnG'!! emih:. e.ren whenl anifm>ahl are lI:Iirrf,emd. It islhu51lildi~,e of genetic dififtrelilc!S 'n '~9Me;ralvigpr" 0) and h.1!)IriI~hirilglrn '00 wilh delt:~se aganrut • '''ded!i(MJI~ agiel1lt iin !l1Jl~N!1, ~r:.!l<~~ ,gf tIl.e- ~~~ ,~'te!lOO gf valiirilOO!!1
'gi1!I'Iiil!rillvi!Jl'rlr
f'OOI@!i!II~Ul:l'l'lil'! trileJllIIlOOl!!

'l:!rIe~II1!' I'll!ldlYredf~m the modi'lL (B) M.,i!il"lllfli! WE!~g.lnt R~rtr;alI!srorm.w~'W~5·I~aIIl:~ Ipa~lli!: c:@llS<ily .•
S1riln x paraw· deru.5iy:f<!.l!1o ::: 6.00" P
I:::

o.:OO(g;

p.arai1t1e de1l5i~y:i\1'l1l :: 8.09.P·:: 0:0053; parasitl:! clE!fl~: EU1!. ~ 34,4, P <: 011000.; 1Irli0CiSE! ma~rt .1f:<1l1lOl = .'2..16,.1" = O.:GB1; iYitial weight FU!!4= 140. P . ..:.0;0001; .;:I1i!d ~perimf!lillall)tcd:: 'X~ ,.., 18.1., P< 0.0001. S1ii1ililxpar~m dem~V !f4.11)5 ~ 1.2.0,. .P'::::::
031]1 ilIlildt!lle Del<l:rnoo be,:lweelil bbcl!:: .a!lld :ma~m U~':" 0,2$]1 ~ i~ot slgn&Ii~Glt iiI~d1i1I1::SE!' ~$

I1Ji1W1!r5Ry Q'~ ~dln'bl!lrglh. W~t .M<i~m i!llIad. IErniliioorgh 1E.M9 UK. ZOep:armenl: ~~ Animill. [coI.Ilt'!Jl". Lund Uni~'l<i~. [OOlogy ,Buildililg.:22362Lmd~ Swedeill. "V!IlowilolVl ooi'l'e~polI!de·,if!!l'.e· ;~OOIiJL::I a~dre.ssed. [·m~H: be~~rI~~.

~ln~tl~J1jt~ ,d' 'E¥olllliooilr:'/ ll.i00l6g(ll and II:I!ItiN!i:lf! or 1rrn· mlJj}Dloy~ ~ndl Im~ruon Rt!5@Iif\(1i!, 5(h.1)~ 0:1 molO!Jlr.a l

~m,

fPr~en,l~d:ara:;~ Center fi hfe(!i~· I)~~ 0:yI'!<!m1~ I~ p~fljllli!lil~ of Bl(llogu ~11!lI1Eiltl!l<m!l.etgy. IPenl'l~~l'li!nrn S;lBlp ILlniVl!lflifl)1, 208 MIlIl!IlE!r lom .• IUlniir@Flity P,a;rk;. PA. Hii!102, ILIIl.A.

I.<!t,!:,~b!:i9@~OO~UlJJJi~

al1:d 51)! 'it: (aGl ooly be ~Q1Sur~a~ 'OOIIIfIpaf@~: amlSS ~''Ol.!PS; cf anilma.1s (l.n.iI1ti!!~ 1", Irnmm. till fll£im!lnce:.it~5 mal: !~O!lSiMe:ro loompanl U'~ook:ralil~lil'llf 'I:wI:l TliIdMdlYalh~m., D~~l1IStI'atflilig 'Qen:etk vammnlf,OI' wte;rrclll.a!' diler,efor! mqlillR~ ttJ .. t dii5&l5e llWBrity Ibe ilMe~ in iilliI~lIIiIills of [h!! same gero"e a!)L'i(iiS$ .ralilge 'llifinreb'il:!il ililim<Ii ~,; .ill dliffer!l1(l!! ilil slOpe ltieMem 'gelil~lldij.
,~.ti1!!>genNii~. variation for t:olern!llil@e •.

h:as;m bl!! defined a ~iII

W!il·r·e~@r'~f@
iSo1il1
Cl>~

:lill®pe.s.ilndl beca,l.II!il!!' tI1e· il,itial weiJ:ilht ,(the' inmliiCl'lp' dlll]i~1 I~~~n st~aiills but f'of' thf!

@):_ciudoo. fa I'a clltaoo til@Oampalf"

pr'e5ent 1JilI~I!l()iSJeSisilll!i~ilfil'elEwnt milfl ,e1Jl,eotWileill temgf,oo rrui5la:riIm~ .. lrIlIl to![err"linoo,. tile r'eNi!,rnom noi'lil'l$ rD.~ 'IlIfelgi!it Ihave been, scaled ~oiffilatai~1

g;ene~e;SM'II\e- anrnerapt OfZE!f.D. DBA11.INIIHr MI, CaA, and! (5.1 ar'i1l ·l1IiIe ,diiff·erem om!! ~i1Jalmis..

REPORTS
iliy U.. Q!1! ~f~e4A9± 0;88 (_Q:~1!!~~ SO) ) "~c_""'" ,""""t. """'''''''''\i'' ,Ab~~" .~A;UII"""l" u"'i ....t g~It'-~I!L'-~~-" ~~'~~~ ~1i','",_· ·U'l:'l!!· __ 00JLI:18d! 3ro1lrd,dillysW ID ] ~;. un m~I.60 ± 2.89 wys mklr (Jmpeak ~ile ,dcru.ily {rlg:. S]). To. Imlm, v~mL{Jnil~1 i~~3jM1g mUl.~ ~l~ \\ll'i ~rJhm.~ a"aI~al.y~g Qif'~ p,am.-.iJt~
@rn~!'4
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~in~~g) ~)i!1~!rom d~ "!~Y5~

&ff~~ll ht~Q!1!t!lte!~ly illl on;ltlOO m:aremlllext), ~l~res

QI'~.

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QfgJ~~e ,ooN:!].~~ir!.~.Cg!~",t.gt~~.~~~g~
~.lIiWlltllI15 by ~lI1iIiifici81 selcOOonOOl <iI'~ 1m.~1i> IOf0111 torol.~c~il~ 'dll:!' free oJ

~e ~~.

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~1.e!lq"l5b~!I!Il!.!lCeyi~d hl.~'OY1~

IrF4..~Il!~'I 5,54, P <: 0;000 ~J,ilII:d piI!as!te clm1eS ~f2,~lll ... ,64.8~,.,p < .0.00011 bl~ld:lCili'e "WIIS, no S'I.r.1iilhl'" b"y..cl(Dj~~ 11fltlY9C.uom [F!t.m~... 0.651.P= .0,13]. Th.}re was!l~!1 sigilifOC'.a!ru~IToolof Cl(j~ri!~.oolfll bb:ik b:;:l: = 41.4.1" <: 0.000 ~.Jl,\bl,l![ 1l(}~Ii!II~QI~io:n$.oon~l~ tllockalld ~ina:!1dl·orcltr.·H~(P> O.2S).l1a, a~i!~ ~revious ~~dies {2()~, 2jt nl~C .Slm~!$ dlrr~cl in resislmlOe, a!!d p<DSile clbile8 differed ln~lhein,~ rl:lCliOl~I~JlCIWW (hat liIlIey i.l!ldU:xJd., TQ, 1t.C1St goolltic:mritui(IU for for ItotiCnllCC,. 'we ~1f001l1cd3I!a!ly.G of Ixainm1tlinl DC'cl.GIlIlitymd,
!~lirtifl"Ul!I!fi "\~~''1l a~illit."l ~ ~OO OOI~ty {OOU~ iinear <ID~ ,~,,~c ~m)j !'!]()~mf:4i!l!. lhefwimIteu~, <l!lJdll p,!lI.a!lOCldatiouvWlfCS ofR-Be den,.

d~~ty ~n.o.t ~~5tmJ[i iil'ld ~~[!l; ewe. !halt Pa.'Iia.. d:;i!~~Y ·dlm!iW OO~~~~ :nlJ"~e smti!~

~1i5iJ.y fbi" ,_I.~ 1"IlGi;l~ ~ lb~\Ya.~ 8i,g1tiffi"C;,iIil~ 0" ~~ow· a [~~~~ ory;eld ~ "w~f1 dL'(;nJ~1l~ ~ wrre:~ti:oo ibHi;I\~ IUie 1~\?o\O!~~ of ool~i~ ~l~ri~~tJ]!\iI!:d~bttlc aA~ifOO.di lk'll'dli~:~ .read· Hy h,~bee (0 oon"lesl!ic ~intils wJwre k could {Spea:n~,'s iI'lilk. o~t.l!~o~ I;' - to, n - 5 1~9ii be limed to wi.1fk ooIO',lilfLI~"1 seloctL'On :~giCs. runinS:..P -c OIlS) l1ucwetealtn ~~g)~if1Cal]111~U,ve

To 1m wheda ~~~ b.m'~lilflJ!es oflobm.lIoo 'WU'C' o:lIrd~ \1VIilcafa.tla.ed. dl.\l :s!~.Q.t" mi1i~lmli.ll]il \"1.,-t~'i1 ilI.'d ROC kiilSlity a,~1I't."t il'il1i ~ p:tJilN~~

rer~

to!} as "~icll,{lc" f18l]cookll. ~lilCrmI.ea v.a,. ~"'ly()f'1'1ilrn (;'it .~ ~rrn:IM~O~ii'li,l.S; ltl~iidii.1g

wroouOll

~is.tIm;: [oReIlI.

mirn!aool.1$ 'bi."lLWOOIlI rcsiSl8l.~ atd, oonia, ~liI:'I1lSof roImJ~ (r. ""-1.0, Jii = 5" P< O;Cl.:5ii~ ·~Q;f Iiliic. oon~ru?i(, ~.OSil.ud. \~~:Il ~) ('Fii} 3). DBA. !TiIi~r;;, .

1m' e~'nple,. W'ere~~

lo!mu~t ..r~d ~

re~~la!l1

illo1!l CS7:s,,,,,,il~~1 tW!"e I]~. 'Cl'poiJISile. Uw,reduood

toier-nUi is: <I.'co:;,( of' resi8'!l!Ii~ealld: vice vmaOtll' .slridl.es~lIDmlr<ll.l2;dla~he rolloollWil!ll~d. arufll,ytieiiJ~lrn.nlCiwork d.evcl'opcd 'bJ" pbnt CIIOlutLcn· aD)" blobgislS Olin also 00 II!E 00. ~, fIiNf!3~ gl1"lruc \!"ar.

J. Of9: rva/.. ~:Q. l'l"!i ~1994). .2" 111"firntblilrm, M. 1R.a~i:ler" ~1Jle 3:n" :5iH U'9'i!5). 3" J. Filnn:iFii. J. lr4uiil2-F~ rI[lll. ~, L 1l<IIw~liIe.: RiiU!lti~r, M. [~~ jlfl.j..,Ol'g, £~ sa:, 1,600, ~].o04h 4. 0. ~~!ii~1 ~~I~ Am, lI!~t,~64" 1;9:0 I[:;!QJ!!I:l}. 'c. 5. 1:1:. A. ~, .~.IH_ II(ir-d~II~, Evtil- MI. 1_ Otg. fVp.t 1~4,Sil (2,OOiW.
1. E,. i.. :~ilfiiifl!!. J, TlrI~@tt .(val Int. s t;, M.

R@'mr,i!IiI:tt!5 "Mid INotes

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S"r~yor wcilll~l In. !he ,oose af:OOIb ROC I.md \\l'C~ln loo;;,lhcre:\~\CICh.igJlIy Si~nifmnhill~i:flI~ beIn.""~1iLiSrrall~ .alllcl!~m d~.ty (FIg,. ).TIw:1~ Ihero 2 ~l,fas ~ioo. 31~I1ig 11rH:Y1)E('l ,iSfr3insll~ lDl(lt:'dllOO
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TliIi<i;O~cl!'!sLal isro'~l01111e hldm.i!l!l ofp_m c~m!Cg; :ifl lille ~i"'ical ~I$, IU!C exClEm~ or

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TllC exislmJ;eof~!:lt."'tLcc~tioo .wei UlI~crn!UJ;e 1~'IeOl!l!S ~.h.n hoot del'im .•. C<!!l l:akell "C wmety oli' cvdl!lll1iAltwy mwertori:M; lim I~:t..~ to pa.d~~~mre, 'TI1(~ ~M:isIi~ 'bmis,ofd.u:: g(}. 1!JI!IicV'Ml'I!mOOl. kllrile;li'JL[I'(l'; 'llN'@re,pM ffil'l.'lllJns:IO I:im tkltm1milGi \{ufufirnl~r.ltol£lillaoom.~.as RiBC 'oook~ {JQ;;ut ~<;l;l ,(;jdlCi!' lillie fl'lgl.i!~ i~Or!OrR.'BQ; ord'le r.llie of 'b!J.n!!.!dJoo. of RDCs 'by p~tbs mdo:r ~oot in"llWlOOle ~~ "li'RS H1O~ SIJ1Iim.1'ih!'oofl'cilwia.li1 bed\\'flC1l m'lcrrul.Dl: n~.:lIS .ru3C 31id WGlgh{lo;s ~st>.lillriillklre Is:I.'Ii OOi1llllllOl.1 iI!llldcriyilrg 00« 00:~1 Ille'!£ l\VO ro:m~ firIDI~~ Illfl.~.ZIlI~\'oi~R;; ~~te ti1lS h~ '001::!~ S1l!!di~ga'!es o;uuftr:r:in@: djis!e;;L<'l.: lQl~ce 1!Ol\'Cyet (Q!be idk,l~lifioo at like:nlOhc.ldar ~vcl {6). In oor dis~ n_~,re.si..s!<lm:c !!ud ~kr!ltce \!.i'Cre uaclbdO'If~h'l5~ cocIl olhcr{Flg. 3~ Asimilar tmde. aff~asr-r:cvioosly OOt'J1 drnl.K'JIlsttIltCc:lin InlilC:OOOIfl)l~ af~~al1def"CI1.trC 3.~iJmt 1~~'i!lOi)' (2],~lll1Jle m~ 0.1'

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Our Ihxm.gs.~fd~ hil Pfiruullli. ittlpli~CitlSlbr
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t~oot~. li!eU1!':aIorlposunve eifa;:l~ n,us, fe~S!lll~ ,MfI!oI~ .... ~:a. S;, A Biii~1;, C, A. MDrris;. ~. J. f,a(aw'Ol, 26. :S:S, U ~96t MeG :11il;.'e ama:&I£ cffCct.sOtl d'£~l&.nli.olqgy of :29. W'I:Ifl[!!~~. , GrolMIi!'I, H, 5.rn.itb, ~!1dI M. '~tj:~!lIl'!q~rl !I!l~ A ililectiow ill.~ (5. 7). SL'OOllKII, ald. ~I~ I~ 'e',;i)ern;jJ",~ di~~!!!'i~~li_ Th~~1il'!irk wa:o ~!!I"~!!! 1.1)' th~! ,a]\'; 00I111mtl:lf1~y lhl.'I!Ig1iIt 1[0 k e.llgaged in. aJ.ua.lPlli~b ',,/.ellOime, lfl!i~t {.n.lf .Ii:], .a h!arii~ Curii~ Mlm'f~li~P' -o.oa:--~~~~~~~~ . ':2.5 2J~1 115 Hli 1iI,5, (,'O.:lV(lhJ;WIl, wi1{frC ,~olurtkI:LII. ·of ~~. r:e>;~, se(fP1fo·~0]56t'~ ~LR.t .anillile Sl'tl!dl~l! R1lSlli!Il.h(Q1!i:fi(il (lift), 'Th~lMliMi"\'i\li~ ~~rI~iI1lihille All 1Mil~ ~t tliil! lec$ror !;lQl.mrer.N~~s [!!lYle ~i:e,,!;v!~k;h Resinstance ,(111:0. p;ua)!iiI~es~.dx.110" WI:§'!tllsdlilftjIIDIII~ .W 8~.rljll, 'Thlt '~p@l1fl11!llil[till t\!OF~ '~.iI:i 9it~i5: f« !!l1l'f'l'Ved m.~~ce!!1I, l~ I~Md 00 Q!I!, {'l)OO!:Kte!lli ,om ~,Nl1j~Gt liGNISll 6~2'H4 ~~iIl1i~ed by tl:tt Ifig.3. T~nfiIf betwe!liiiOOleiillifi~e: am resManre. ICldlng JtoOl:;en~I:d~ 110IteqUilibrium ~,\lIiwooruy Ii!~mt Orlir.lf!' 1M1!;:I'~r Iflle~,§pi:~e; 01 tliltl· IJ. IK. ~JIliIl1!1'i'1J; 1~'Al' mreWartioo IEtweeril r'esi!il<llu]e l~jlil,\I'Ilrseof peak C dyuwwics (2i). iHa'wcvct:, 'toImi're does not ~~VC,ri1 ($demtifi~ fAKed\:! r'e'~ .Act ~i; 9916, 1 llf'a~~te dMirty) and m!~afl:t1eim 'the fOfl'l'l m: mllnl .. 1!lCg:rti!'cc:H'oo.('j~. a.cfifli1.es;:of~~('l p;lmSW; ;nd. so i~ a ml!illilil :RBCdenmy ,GllI"ilQililmctkllll'{1Iiiat ~l5.mi~ranoe .SUI!hPD,ni!l!JI On'heMOlltcerial IriIlIsa:smedas; ilie :5Io,pe ,of <IIr~il,llId~ IriIlIillllif1!l!llrilil mi~M~ ruel ilII.tn~('!Ili~ic ~!tr~ioiil. im dJ.e S31.'I'n~~IDy 'wm'r'!l!H!;II't!!l'IEg.mJ!lih:si!fDfiI~]jjLittlLli'3~~J!I!>&5.cl[a:l.:2'~D(l ~ l~I~~~cliof ~~I~ C~be ",ari1lliiOl~ror .fIla!m:al .~1fH!I Me!~tm&, ROC d~liI!lijy a!:l!Q,\llit pookpa~ OOJISity). (8) ltan, d~refu.re be I~OOrjlo allO'i!.! sOd Sa:!AI'T'~J:t k (o~ijoo l~etween resistali1~e: w[er.tuiloetlil the IOI~ ami frq. S;j[ of :hos~:evolu'!lo:r. ~al wi~1 tilJ:~ntlaIlY&!111Xf1 110 ,of minil1f'lL!lil!l wel1glll:. dUlring in:fedJ:.on l~hiM is, !l~~ee1ilC4'!~, r ~fg!i1al I~M'~~l!!S thilii! sroi~ Igfa ~J~(!I{! Q'f M.]isti.eC(l;ei''Q~lJii{lll {6}. B~I;'l! mrol\tr[~ t'ID.!ogy. II.htlm is !I cllW' mrililllifi_ wei~ illgailnst~k parasitE! elnmy). Pll)ctI:s, d 3'0 JIJ 111' 2:lltll7~ a((!!pI.!!OI 3 OOlflil>!!r 2J)1J:7 1)O.1I.12~dftil~!!.:n~~:M i!Jll~. klI rerog~!ind !!~nlllld~.C' lMlOCIn'IPOiiili'li.~ ~IhG'l!!l' l!IiIB'al1l~ ~E.M 'w:r I~ch mousemil1l'.

+""'

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~m~.

814

REPORTS

'TARIP,Auxiilisry Subunits S;'wi'lch AMPA Recep,to,r Antagoni:sts into, Pa rtii,illll AU'0 n iii sts
1

,~ S:ccl~j p< OJl5) \~~ = <l! d~~i!~, ~p:!i!tY;h (~~. ~,~ 6, ~ pA i,Q·193 ::C ~.l [w\., '1 = S Gells) (Pig. 1, A a10CI .8) {.f),~npil)'ing hn~. e.tcilahi~ty of~h,c~ p~~IiJ::ifllem.cl1llro."Ils: '!.1CrebeUa1iGolgi eells

(8). Appticatiorn, o:l'CNQX

~.iiI~

to {'jQ>igi cells ~'C~i9h~y

i':L\V~eilitnti.liltl:il~voll:'lS~-C~~Ili}~
Ii = ~ I

(...;;n.9 ± 4,4 pA,

IKarelll MemUlz,:!:,2

IRobert M. Strlllu3.3;~, Rog!er A. NiiC!Dll,.;l!.,,4., IFramlll:l!ffilll .It IHlay:?

'Qunm::a\illledl'ofile IIlOI1lllPOOirld~ w:d~a:s, 6-qafllO·J-nitmqlll1inO!l!aline--2,,3-dia:liIE!i '[(NijX) ar-elhe: most: rcOO1!)l1lJQ:liIly tII~Edl !).,pmin;(l·;!,.[bydroocy·5-ro~hyl.~.;tsoX!:!:ooI~liI'rq[!1!iOililk~rld (AMp~) IlIE'(e,ro:rr af1ltggOlili~ts. H'(f~~r. we ~liIdl that in ~h~pruefire OIf tr'al!ilsmembr-a!ii!';l AMPA !1eceplto!" J~glJl~oo,ry IPIl)'Wlru;(TARFIs), W:~ich are AMPA I,ec:ep,tgr ~1J~,inililY :s.'l.!bul'l~ts. CINQ>:: ~mG~ a pa~l.ag:ooist CN'QX,~rld!il~(j1:S!l1la~l dellil®IJ~riiilTl!Igl wu,entsglllilltUWI1IS of th~ ml'lrriilllervoos ¥mm., and rewrnmM:iol!l orthiS:flgom~ ildNity l~eq)Llired wexp:w..siOin ofTtA:frtP5. A ayrn.l strlll>wu[1eof 'ONQX ooundfu ~~e TA~P·I~ AMP:A rm;e'~r ligimd· lfulimling dknmin 5i1owoo'tlut. ,aMlmttllgh (IN(,lM 'indu(e~ pan1ial~dom:ain dCi!'SU~e .• this mO!Jem.~nil: I$: 111m. ~~!'lln~tI(ed ~];r1:Q lffiniker Si~ar~tiiliil., '$I!lggestlililgl ~hi3'l;T,ARlfl$I~Ii!Y il1o:-easeagooisl: Emca,cy by ~,1:Jie.ngth~n!ng 1I~~(!!IJl,~U!'l~:~~11W~f!1dOi~~ifll'~c!s!,Ii~e ;gnd (;h'aln!l~1 '@pening, i('1YJn1!'sutt:sd\,)lI'i!oJi!wat~ m~tU1e- ~~!i!Ql' o,f ~f!1 ~I!!~:b~y~bl!!!~it d~fmriJi!~~h~h~ g (,gmpound flJf1cti(l!i!':; asa:!I! '~~!i!i:rt ~~ Ci.:!Ji!

~11il,1YI-o~ru1:i1.1.e (NMDA)

~CI"tofS~ A n~~or lrl~llUl!I.gI~ m.lilmffi.C'ld ofe.~latctry ~¢fmliS-

E~~8~;~:!~~:~~~~::~
of rollOlI:Up~.croce~:o:rs: AMPA iBRiI I\l;;

~ma9~'t.

c~ns(f~g.~. qdm,,",rc\w.we fo\!i~ d!iala!!lI<J,S.Q!l'~1. i111,g AMPA rucqplnrl> dOO!!n(l~: s~n~ly lleadl to d~ po~arizg~iain,lhooalEea.;I'pliealioi"l. of fiY.i<J 536.55 {IOI.l.Ml '\\\&l.ich~sa.liilOUIOOltlpetilMc; A:MfA. K'C~ al~J'Ii!iit (QjJj did Il'}'I .ili~ <'ll"!.• w,vrod CU~~ .111 Go~giceIDL51(6!j:. SI) (l~",~~~!at O!~CNQX:",indJ~~ d-epo~w.JltiOill\'1ir~ lIOOocCfuCIn 1'"\iUnhIDbu~¥lic i acid! ~YfC A tTJABJ\",),NMDA. ,Mdi ,glycire ['OO~ tor ,atn~{misls ,as ",ella'> ill ~otrodOCO"Mrn.cnX) ID block Iltlt'\:\IIOIdI:a~.vil?J, 011:' da.flii :ru~SIOO: Jtilat
GNQX ~
1:IOt

~!oo:iCld oopi:!I~!\g

~~).i,idt;;:al_iil:ga iiI~' clT'~l .of CNQX I;lf) d~

:iiun.'Ip!y ,aa~n!!:~~rooghl.'Ilil.(lHffir:b.;;,1!J,. 1

7..~\.!I§(l'latmlde· {l'\IOOJI;;}~t~y and 'scIOCAi~ly bJoc'kM1IPA ~I(II!s1!I~d ~ave :~IlI!1:di~l'!able in cl~_clcrizjng CN!dittl.lrlfy S)'1mpt~ u:lI1ISlni£. siooinlhe ('Cilurru rei"!ill¥IIlS~1 (eNS'),

AMPAr:t'O!pfOfall~~iSi: corum, bbokllile CN~ ililduccd dc,polarriZltion ilO.1. wl1ctililer .% ~i'!,I"C:

b1iJ1 hl:Sr~dI mJual CNQX. !~J;'J.ct as am AMPA m;~roc ~~:m~!st !l~~~ O!~ oeU",. \)b I1eld'cm 'Ie..~ 'WJilciJU1!! ''lCIllCOn~~I[~i~ pn:~LlfIIialc:OJCm~rlOO .

[(mal ~e~'r

.As,ro~~ilw'[l 81~~kIs,q;"tlillQ.'(a1i1l1,,'dbUltlS of~: qwnOl>l.~ .'nlm.ct with .AlIII'A il:l!:l~lDffi'lJJ. 1I1!1e .!Sa1il1e' fuilrld!tng aiiJlooia'le ~~ of (i(Jr!.~iti~·AMrA ~plOf ~IM ~~~ Ith~)' ooc!\ti.dlng 1Ig"OOl~~ bim,· iAg. U!lilikeagJ)niM. ... QQ~~ltIw ~lI<\gQni<t.'l ~!m~ <U~~rlist .. m 19&5 (1-3). 11~ dn!J8S~N"Qx' 6,7-dlIl~wmo.x<!ILm.l'·2.,3=db:_~ ([)NQ.!"QI .. u:I 2!J~ no cffic~y, fM\lI!ung U~ blndi~lg dces.!1.ol ~ei!!d. 00 q;lmllng oI'h io:Ul. d~j]j~clic.,. gnliimg)., ~itc ( (he d0Cl1'ID-6.rurro.l,2,3;4-I!';Imi~Il!lO[fl<f:liI10iX.31iIil!.). OOl1l.':lnt 'M~ 6l; of ql'lit~ajjJim.mnl'S as

all.0IlIl3rk:millaiklliOO1!lkl

19.1mlm~ eams wk!~ dm diroo.~

PU¥:i~I.lb:ll]'OI'l afrn::ttbfillar .sHc~ '\,vidl 'G:Y~Kl 536'55 bl~kt,;~ llIi!~ CWQ.X.·:indl!!ood CY~I (CNQX~ imKl'u!ced c~nt iID'!. (iYKI "" 0.4 WilS pt\" II "" .S cells, p « O.ooil, as 00011J};Uu;! wV!I~ CNQX 1}~,oo.eD' (Fig. lC) Fl.IIitbm:uKi(C.llM~kro1D1C!..1~d.e (J.1O.()

or 0elllbr gOO Moc~t Ph\!lrnrl~o:jl.ogy, Um~l~ !l4 C;ifl~ .at S!i:ll! !1r0!~~ ~n Ff.a:lllti~O:r CA9<4.1~,3, US!\. ~Gra~Qj;1! I?mgrilill iI 1!l1!ll!1i>!:~~no~ tnill;l!I!'11~'II)jiCi'Wfornia a~ San f'r.nci!im,ia'll Fronliwo, rn 94:ll.43, UMi.. lOi!pillilrlii12nt mi lBilXbi!rri!lIryand Bimph¢G, Uni'l@~ty ~ (~jOOrialiiil. ~~ fl"ilmi;~Q, S<inFr~ri~,g), 'll'4143, U~ ~~i1.JnJe1ilt {I~ F1ilyr ~Q~ UIfliw~lly 01 CitifemiiI <Ii :~n~a~ .5a;rn Fr<l~lJj CJl 91:1143,. USA
'I Oepo!!'!r!'IEl'Il

Al\,>j"PA ro~r

U'l~~Lt)'1. !lf~\!' OlIrll'I;;¥V"e ,~~<!'t1~~

{:5DO~lM}, aposiu'\iIt:: n'OClld.iJllmsbdU:li'itiUy isil.wiw 10 illiutagmllS"lS Ii) smy S]/'I1i2pu.c 1MW.1I!· e.yc'lodllazrd~ (10,. U~ int::mlSro. 11m ~~ 10 .rl"i il:d!«!!~d)a~II~ oo~ld;; CNQX {-fit? ;i; 216 pA, .r~= 5 ~~iL\ P <: o_m" ~
OI~ iiil! ~~

Ofgl~~

oO!lI~d

\"mi)] ICi'{QX ~!ooe)' (Frat m) Tli!!ls.

PJp!!l"i{llJs.ll.~ not Oil! ~~ ~ II'!~liS (4 .7). TIle IIIlxil'mlli£~l fur lIDlisC['OCl ghl!!l£l gle'(p1arJm;d. 'Y\IiIrlik: litJiXIi'dlimg ccrooollfu:gram1ll: celli, 'We a~oo dJ~,d.liiLt !IW!iicooJJU of CNQX. (11:11JM)ill? j

'i'T~ whOIfl1l'~!ilIr~~p~d~l!If~ :~Ili)uldl'~ .~d\ire$~@i!I: ntNld'@_ mS!J_ocrl ..!i!lIll!I (ruutl!l"imlr@nlll!l,lJfsli.~d!w '[ItJ'bNJ

orea;oo

("l!iPSC)

spornMooti\l~1Iilib1ku:y ~<f)illaplic OI!lmlr~ f~~I1I~.cy (0:22 iii o.07ID Ito L5S: {D;S6.~

CNQiX.~~. !!:)·m ssaa ,.gooi'El (J]"l treseA_M.PA ~IOOS, deoplle '~[!S lI1fC\':~(YS d];'1.!.ru:I.eriz.1lkul 1!;S a ml:1pCUIJ.'IIIC affil~:miS'l. .AI~rol1gh AMrA il'eCeJ!l1Ors am' ~p:e.'>SOO ·ow 100SI;. if nd. atl, nOOInlll'l in die brain, 81oo,polmrizil.1g a(llJiOll of CNQ.X ')i'!~ Il;(lf p.n.."\~o~ay~~ fur
r :

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:2!' ~
0'

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e -G;~II

9!}
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5

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10

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o
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CNlQX

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;I;

!, -ao·.

+
O-"WCM

'i
i1'.'.

~Q;-

"i'
~~" ...

'

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..

GI

roCl
.•..

..

111m!! (mlFl)

15

'iI~I'

,B ~1'OO'
0, - T~I
_"'jFT

~ -~2(1.~.• .....TC .,M..,_ ....... 1, .... .... .

r>0

""F"',...........,
10 11.5,

.... .'

,~ -t5iO

. Ii'
· .... · •.. I

..

~ -eo")-~-r.....,~T,eM ~ . II
0

*111.
r

llme trn1jlJ)

is

_.,_..,,........,

TIiT!e!(mi'i~

1®

IS 110 i1rne (min)

IFig_ 1. Depof.lllmng runeD"lt Ie;licttecl' by' I(:NOX~!iI 111191!1r"H5. (A, ,ami Bi!1 lmIe ffir~ooncy of sIIPS(;s, 'inl ~!tJiebehr ,gralilyi~~ (,~~'II1~taJ~-dgmpd .ail: I) IfiIii\( <lInd after ba,1iIiIiIlRllh;ilI1iolll m (NO~tn,= ~ (~~"p <: '0.0-5). «(: ,ilD"lcI DVilhE1l~oflljl'lIIg cunelilt l'IE!ei:ledloVl)fiagE-daIIil1il ICErebelar Q)l~g~i CElls (GoO ·tD ~!10 m''II 'W~, measur,ed as (rrIN:;!>!: was ap,tiHilii the ab:sen~ or IX'e5elliCf! O'f either 1.0 J;.IMGVK~ !i3655 1/1' = 1l,mal.5 cells,re:!p~'ty', :P <: O.oiOI1!.) (I lor ~OOj!i,M fCM '(rJ =1ill (

[ewt.'i"1D1l PG~nl1lp'lic currelilt '(EP5C) re¥ersa~ pote.l!It1iaU was, 11fIlI6a:sU:ed befOf'e

ilIlllIdl 5 (ells, respedi'J.l'e~y,. « 011111.)(0), ~E~ S.llini~a:m~li,(N(fJ1(Wtl$ ii!I~~ti:edil:o hipPOOln:lpg.~ CAl PYl',gmidlalo~~ ~FIyli)in the' P!'~~f'lQl a iil~ab~liI(e ,of"liOtl, ~ .'" 50 ('£lis. forea.ch 1lr,eoiiioomt!. '{IF alflel 6l 'CNQ.X 'wa;s'fdsol Clp,~ted to l'rippGUl!lrlilli.!l. d\ElnJtare gr,lITIUlJe mll!J; {OO) tn·;: 5 looIlIs)'OIlidi j),l:fkinJ;e (IEllbdp<] ~ 5 U!1l!J)in the p:reseilillEl olf w"CM. H~wo~T!lpal lilelll1iOOi$lNfre ~ttage:·damped at: ~jlO mW; fllilrmji! Il:eJUro\lilswer,e: :heldl at -10 IIfIlI\f to, IIltEfvern: wttag;e: escap~. Eilfor barS m (S) to (G~'i1d;;mte.9EM.

81!5

REPORTS

nfj. 2.AM~~ !'tooptOj' A c!.S.x ,($. 6), T!~!s~~ .~~ ~bi~~¥ ~mt AM!'A ~~ on h]~RI.®'1S ~lCI"iV d!f~ amw!1fi'm by (NQX and IJqi,IQl(, bl!lt: :Ellot N[B!QX. fer fll:mllldw~ 00 ather '1ype5. afrnelU1.!!). ·\\·bdl~ rom 1cf;lOO. whcAihcrCNQX cal act ss aJjl agonist un il:1l iii l:.~iUlrcOO~Og S SYs< terrrn•. Wil1h!2! c;h'dnge ~:1Il AM]1A I~~ ,(IN;~OO 'by' m.iip~l. CAd hcldili\lJ(!l!Im:!rnf. elicited [[i~mda~ (G;t~" 1m~.~~i1b~b100 of'JiCM; ("N.QXdbd! ~o1 ~nt~ ilifi iltW<1td~t H.9 ± 2.lj. pA. .~~ 5 bJ a ~f' ·a~pIl~OOI 01· = 10 p.MCNQX:mwb~ "'Ii",) tr;" ~'E\ c<; . ..~.J : ."!vl "!;il eeusi !FIg. . ~. h .as ".: JJWLJ t6 !il), \'" . "'J' '~~'mnlit)~ HOi.?r(Weij<I. Cl'\'QX~!.i.WOl!dI a.m~!1l\li,~ dls~'edlh~, Id l~resii1~ G~'R1 I~he~I~ o:fliCMl. Ho.1S ± 43;3 pi\, rJ'" S re'Us) !lop .aand "t2~.rw.3iS. ~I·· ,EI'!DNQ)< {F~. A CNQX"inwcoo ·e~1 ''!,!,'3Salso .00.~refi! in the: ,absi!!ncr1 Ireaodl~ldl('jP:~itOO' o:fTCM iil'l d~I1t2It!(!:~lIl\(: aJld1 [~re' C'rsoo! .!;I_M C~~ (;..] 2,2: ± 5.] ~.I~ = 5 c~IL'5i)F·iIl, .~ .:;'ili~lliH ( F) 1iQII,: .A lbrief ill:Wlicatio:1II ce~~I~r PtLl'k[vJj,~ c~I.<oH3~ .•7 ~27.J p!\ rJ =5 'oW :m mM g:~ll!Iti!lllilili!lti~ cells) (!F:ig. :IG) .. Gl'il"e!l~'!:OttQ\fQXoooldi ill!dJLce (GWI:) irliliOM Wl:!S [~'I:ie'r d~larizh\S 'CI.m~~ns~ an In~['OO ~YflCSk~lledl, d'te a,pplioo (a .~ 6oe41~~I. h ~listadi~~y oil' CN('JN: is: 11'10:>1. li1j,jelYII.~1!MIl1 (8~~e ('NQ~':'ii1!dl!l(ed ~~y o:fCN!S nmrnlls 900. J\M:PAI'O.'lC~01S.Tbe I~!ianglein lliioklht~ c~r·D! ONQX '1IL"!,.fioo_dy 1~l'd~~1k. of ([\:terti.en of 'CNQX_ ~e:JirtWdIS mei3iwrec:i '1Je.. in&~OO(il.umM was ~~. ·ti~ly~~ CN'Q,X foIl'E,diuring, .<Inti ,af-mr th~ gPt~UlCatiO!il Irlf 100 'W<I!!, !~t~. in Ule ~ of1'CM.
~~~ !\I,,>g_~.
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To ooll;:llI!t'OlwiyalliWlule ~l1iullru:

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1['0 AMPA tm;.."CCpiQCoo~.V'aIiiOIl,we nc.'daIJ.CIWptOO

to

1I~(l: 9gOf~i519(}~.vilyofCNIQ:X. 00 .MlIPA 1~1~.:m'S G'<:~in mttll:l'Cd. limnalllmmij'TIi1Itc kklney (JiEK) 293 rel~. A b~f app1ical1{m {)if C-:N.QX ,~V(lkoo 1.lllnw:.mJ ~jlIOl~ Ha:::29:3 C~L5
l~iIixi!OO~U! 1l~A!NrPA ruo~·pme·fOOlliu,s: s'lioorn:~. OtuErI Q)dop<!!1di y.2, 01.'1i!eH~ of he TARP mlllily of .AMfA lJ'i'(tj~(!IrallXilill:y s~units (13;...J5) (-lit.? ± 5.71;)1\.,,,~"" 60C1k) (Flg.2A..~ f,ur~

indlu:ed' Clllili~l1It il1l il'CM is $h:ow,!iI (n ",4 I1~U~:~I. (D ,3!nd[ IE'I The' li!ffd of 1,0 ~!M DNQX !.'inti to j!.lM NBQ~Mf€! ate, meii,sii'-ed ~!ll.Hec29;9 ,ooljs ~cb~~ wiffiI GWR1.11Jililli y-2: (ElN"Q!~ n ~.iIllo9ll1s; Ir1IJ8Qilt fi .~. (E!~I (0) ill1Id i'I G~~i ails 1111 1i~ 9 1 aOOEMflOe!(If KIIiI (ONQX: n ~ 6 {~Ik; NBQX: no :;:. !:I mils) (ro. mor bml.iJl WI to, (1[1 [ndi;·ate

J1M GYI([[ 536.55 (n..~ ·4 cells). (()1ihe H( lliel.(!· ti!i!!ll~hl$I' of the O~:O.l(>

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di£liIllOJl:,filG CN:QX.tf!ldl1!:'Cdi clIIOC'mtin HfJlG!!-l3 o~IL'"~.Dd.:m;m~ip:[f[)~~~ 'eGlt~iLilIi~iM: :wiiH]AM'A I!? ce~ru;t[~IJiQIfI, l1le~'PilD1~ l(I CNQX \,~ ~~grrlir~ i'C1l~llye~1!Ol1'CCd !J]iLlC[)~~ce ot1lC[i!;1If-287 JJ ~ W4,6pA,n- 6 cells,P <: 0.04) (f'f,g. 2:1\). r-Of ease
oil' Ilil\~liiUi':(ml:lnt,all f"Wilr'Er (lX~i'ilW£tl~ in Ha::293 ceJ,l~wcro:mndi eu WIMlile pn...~ of lCM ..C'o:~,. jl1lill'iOO:ill of the: Cll!li'lielllS c¥olrod by ChlQX. <IIIld;

Wl;!t .. t~ ([ .!liIIM)1 iFd~ ~lal:i~'QX :~ ,d~!g .. ,11-5 a ~ial ~~ (fig. .2A); Partial !lgooist3r, !loch as 11l!!!iMe; blld A:MPA ~epcam!l IOnly a kahn ·o:f(hc i1C1WElIkln.&d~ bywll ~f~ :5lIJCI~; as glUJllll:lMd!i:. .M~n·~ cclls, Ol'K'l :53fi5Sb~oo; -=1-;- ? t"'['.i<'Ii">/ «:n'#- cf o"iNii"I'iI ............... "tIr. ~PA -~""'mv ~!)[lI.i~uR· rn---c-- .", .. ~ """'1"""...:1' ~t ...L 00 ~.. ""' ,., , II ~i£(.~~Hilm::lilli\lftrl mmnt in fliBK2'93 cdL.., !!" . g. iii _ y",'~"'~ ........ O. '-!.. ",~ !.IIN!N "'"' '1iI!!: • _. _ ..• !ll"",1"'" IW_. ~ ._" ... 0110111111., a~ ...... tJilmlinelil1bml1e I1ellasalill ,ooe reoo1ralill: ioqp, ilrJl N-~m1oo ,~Dt1naili\!. mdl O3IllJBlD'. lIDw:nare '1Mro IpJre-rorri1g S (D~iIlbilloo: 93 !-Q,Ji'%,.l1 =4 oou,q) (fig;. ~B), ruJj 'he 9 helilles .!lS'~!i!! ~er~ wiIfIj'!'I aJUIi!~Ja~ bi. ~.IBIJ :[~Iild'.~ ,i}s,a! IiIboo d1agr~ and e;nt'd gf' G'YK[ '~fI.'"ii'l;:i!$bk:. F~ru~, dl~ ,w1!cmjI.k1iIilII!1Iilmti ,~ f l),a(f!d[~~~'~~2)),·~!.SO til! b«k=Wbadi d_r~fw.e pr~, eooll of' Cl~R!l~ eUci.ed by C1'IrQXhacli U~e c!JI_n:e:!!t~'!I'dU~Ol~ lIN'hKliJ,,(:()f]fjjirJ!S. iJJ mmalm lilllld dbmiliill 2~.(A aid [B)GlUlR2IJBD~l mlliWui'e in 'tihe'apo iJoogfulamlm-bom.d (l~~) t'ebt1G!!s'ipex~d:I fm:GluRI ~Q)AMr.r:\. re- ~ tPmmln, Dafa Balil~mde; :1!If(QI <lu:l1f'lij, ~d'ive~ '~32)].'GlilrtlD'l'il* ~ rernder,et].;sal (C1~~ilIlli1g~~1IiI ce~:s (1.1 "'4C1i.'ils) (Fig. 1(,) (6).. 'f'JIgiJJber, OIJl"·~11ia (CPKJmOO~. a 001 is l!DWred[ illli QIIiIl!llrli1 ~B). 1~1 dJJ5ll!'E! ~kmO'tEs'!hi! degl!eE! 10'If dom~i'llil 2 ~rnem: ~ undicalJoo. d:12LtCll'QX aasss a.r-wtw agonislim a 1ffiljjj\le to tile .Gf1tJ. ~1E: (20.29. 1.i'J'l(er disitmm ·is. ~lfed be,j~~ tI:le Ca. ,tmm!i 01 [F'ro(>:l:aiiIiJ earn t.el0:~log1;.I1l!l! ~~iQ s-y,snl1l:l •. p!IlIDQIJ, I~ile ·ru1H.E!ilgtth1iM1*Hi.lhe O3r:l!iliida'~ IUilkeu (I:Ha~f! ~) is COfilleotErlto h [prJl'e400T111i\g ItEti(eS:. We ooug'ht tI dmrmLn~ ,;~11Iekr .r.tnherrn!3;llJ~ G~~ It!lrIti!lgi~~'~~1!l ~ ~ioc~h 1iIrJ;i~' I~w,(:e; and ~ _ dI'if!ool [~~ ((lI1 GblR2. (!If ~he qW!!lQ)!!;~~oocli:O!!@ fuJ_rnl~ .OJJoo'h~'C ~~llt WD ~1.5Iructure ~m. (j~QX·iOOuldI smte loooofr:ed as.. ,0iK IiI'iJ1l!deLM rolomd ]11 qi'ilrn). . a a

".100

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99.4 fA, I.l ""

,nicaruy dlillfmn1l m;..ll tilw rom v.4th CiNQX (~2~I.l ±

619:9 pA, l~ = 1] mt~.P == 051). [11~Mt, 1ktlQJ{ did I~O:~ dtcil .. im.vru-d ·~gl~nro iuaHEK29:3 ~~l~ {13.2; :Ii 7:0 ~,A,IJ ~ 9oclhi)t (fig; .2'1)). We ~.~~ stl1ni.la:itefiF:a;1S :i!i! wrcllclhw G61gi ce'llsir~lIie ab~ (!Ilf TCM (DiN"QX: "':1n.o ± 3,.0 pA.,n - 6cemS; NBQX: 2.1 ±.1.] ~J!i, I'Ji == SooIls) (Fig.1E)., 1here,.. fliill\ cl\IBQXacm p1Llooly all. iii ool.npet:~llw AMrA

inlmflsr'CC~. HE:K293,cclts (-34J:I .=1:: ]3oo11S) {f:ig.TIJ1,. \lo\llld~ was fiJI}( s!Jaliis.

fJ;.'\lcpillr <lillt~gollllisl..'i'\~heNas boih (,NQ'X lillie! .rM'I,\QX act a~~PQrtial~c(Jilis:ls. MooGl!s of (h:MIIlci art~wlM:m.mcl! desrnli>llimim
'.1iI!IW ~~.~ .'] A~",,-Yi . .. ... 1 ~'(;ln (1,¢'iI'L;ll:~I'''''' •-il' oo"oo~ ~ctID"-JI:·11
.• stroo~ ·m i~lku\1d itl!llO~rkC: gllltal.l1ffiL'l :~1!:ttcI~imd!.:Ib.in;:1.11:ng ~Ril: {TIJ.I)s). T1!!e5eLBDs 0Jf~1 Qr~WO' Wll<.d!\;'; ~ in a clam15licll4lik2 lill.lrln€f Ow I~OOl oJufi::mlatioaairei!rnllilSerJlCIli,. I~l)!' I1KJl111W;l!ltll of MwaL~. ] li'Tl\lnirl d::lit'IllIlu 2 {d~Jn'ilali~.ebrlll1.~. 11!I!Xl'1
;1' ~.:I

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RE'PORTSI
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ory-8 (~ ::il.. 4" 5.,lIna 4 r.eln:~.ri~pediwlf) .. f:rml: bers in W' alnd ii!'ldh;;aJOO :S~.

:ill:;!: CE!US}!!iiild! GLI;lIil:l alloliie' ('nI= 12 (~~Isn. 0) (INQXAi~dlij~d "'d~dling ( (urn!lflt Cflil1il1l!~@:S' 1111! ~@;~lls tranI5f@(t(@~ Grul! "!lid '81\1il@I' i#!JRP·l'2. 1'~,3, :I'~.

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wnb ~ooL<t OOlW!ty, wco~inoo. die C!)~ ,SiILJCtllRofCNQX b;oondl. lID IntaeGluR2LiBn, ako rof~ 00 as, '''S.I52" (f!jg. le, lnahlc Sl,a.ad. lig;. S2:). 'fho CNQ'X~:K!I, stmllll!lre
O~~I. -6.45' elesed relalL!;lc to d~BtljXJ mare (-1.7> 3fld, ...5.~r> fer 1I'!e t,.t{l [W!t)l~). v.~~~I~ .is (',(tIh~fC~t ''''''1m!!. ,,_~ .. 1 a .~, ..alid ' .... ,1""'_ -.J;l,;Jll"" _J::_._)j'. BOOo'.~, • .m." IiiIlk" ---" I; }er ~pmrntfofl irl~le CN(!iX:':boo!lid Sln..fO!l.tne: {:29'.7 A) Wru.l1<lt d~nerenlrM:n 'd~ilOif~ae'ap1.stillIC (29A 11.)1 m1fm,emng l1ast.CNQX l;l~l'I)' mlOliOOJ1i ... dtl!C: If:>dOi:l1wlin:
W~

'Iii!!p~-- -, -:- :lI '('A~,-:.• n~~.j"'~ 1(1';: _ '!!El,lJO ,~I""'! - ''- _. pp--- ~""1~ """,--g.--} \"} ""'''' dller e!<Chat<lf)! OOl!!lO!1S ma.}' red~ t(lrnpid de5C!\"
~ti:mii\Jnl m(:'NQX~:llltlitlouJ, c~IIiiIit.1II~~I.lilhl:St: 'i:£U,.!Jl> 8Jlres.u]t oflhc(;Np~lGl of~llIip !lpticcwria.tt of MirA lOO€.Pb:U s.t'Ihta~trs (23~ 24ll, ll:ICCIJllil\::l,nl'tm.eOO. by CNQOC (m Gtl)li.l Il"mrop~ '\!,/IlJ.lomly .... % ·of d1l1:;e~1 Wiaoomdby (.'II"l"Qx. ilfl .~~(:; ~3

1 Ill.}" ~11e.3~~bM'I., E. (I, NieLlien, A.1.l!llalMel\l ,Po 1i3(O~II, T', tii!)oore. £.'ien'~Z41. 511 {l9f:l'O)" 4•. Ci. j~8.a~n,~I•. V. Eiltflml, T. llili!l\!,lf!I., fl. Oingll!rll~,BM,~l' flies" !SI92" 2S,5 (jj;9~;~. s, S;, Go Bl1dle;r. M, !F<lfil~ G. t SWIIlfIWlIl, S. ,til. C.u'I-CiJiWi.
WRl~II!i'l(iQ,f09Y 4iI!,. ,30

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~l.oo1!1refIaJ.o·~h=-lml ~il1Jg, aed isdlcrufmuilltOl[" ~~ wl!~.Idili':P*lia~ sgooift .aOOvtry (hal .~~ 00~!\I'oo.CIt:!l!I CNQX~dl ~I~ \!ia'l :S~'~lik it{) l!he~ro of DN'QoX bal!IDd fo 1lIl'l Gt!llRl LBD' (Ca~; mean 'SCJIU;.'lre d(.l'!;'r.t~l- (10.7 [ A.) (115'),. A key -dJ~1l.ce boct,vren ~he Ch'!QX.·bm.Juad LBO. ~b:m::; aed IlaI!iw ~liUSi>:dl.!."Il\ lfill£ iall\1f am oooxp.~ uiflh TARPs,. w.hkh fuldt!d.B'1-2" :f~3,
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lWOuM. ex~OJilIy :3 ~ of C;""NQoc.-±~!ilccd. Ct:lJl'~ iUnt~il, tlrlc8lhsCilOC ofTC1vn, whld~ .is; Silliniila: III t!i»il rrerdb'll 'we obimlV!cd Fi.9 ± 2Jipk\) ~I~ cO'ImiSI, dm weak:cr 'fCMl [pOImtk'1JDhn. ~I'IGolgi cells !itI:fY 100 ' &m tI ~.,p~iooQf 'd~ll'op ''!,Ii!ri1l!.~t.~ if AMPAroO rep~,~e I])e CI'>lQ:X,-mdJlr..r.xl. C!!!rre~ lN!!n .. Ghill.l IJp!tCeplws: \!!'ere rn]~ moo~~)' [Xllenuak'idi .by TCM (Ii,g. S3~ 115 1.l1iC!d~ pcitoolID[on ~ wiIJ~ I~~£ kfliown Wcal:ro'~iilCY of C}'eb.
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t. 'f. H'a~llimato, 11-1. Mlyahwa, Y..KI!IOO. . IMIIe,.l!rJ'eur'Osti-_ M ~, lI~!I":U (2064}. 8, 5:,. I... P<ll~~; ,. (I~n.(!lll~~, '("i!!\i',[1.\i]!le,·(o·[,tfx: (j!folo~' v ffli-d Or(l(iilimrfoo [Slllingl!lf. 8~rlill. :19(4). 9, I, Tilrl!iiM.et ,~1" f!j/JOfg •. M:wio ,Q'je,lrl; .Utl. 3,. '99 U.99~1. lil !{, it lta!OO(!\1, C Q;.f'~~ .t. /1mho.Ki. 13, 3:5'0~, U. 9'9,;lil. n, N. A.t!-tit,ehel~~t W. Fne-J:k; il'Dplly£ J. 92, ,':192: £2(10:J'l. :l!<l. rot, J!", le!te1, .rlt t. ij!!Jafl~l_ ID. r·~r.~e{. W!li!ler, ~. ,r;:, r.;"Ii!:IIr, 41~. ~~~~. :J~. ~6!i. ~1l~~9). It A. MI(J!]l~ S, TIHt'IIl:a, 111. BI~,~,S~iM~ 3l1!:l, 12:51

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11 TJJIle ,Zoo17, am,pte~ 1 Oct.ober .2007

1,(1, U2~ck!il~!!.n~,6:~.]J

2008,

AAA,5, Annual Meeting

14-18 Febru i.uy =Bcsfon

,On bellilaU' >6Ifthe AAAS,lllllllam of D;ired:'@r5. :it is, !i!ilY di~di'nc~ hOIilior to ~!ilVfteYQ'1:! tol)o.S'l:c:lilfor the: 174111 l~ati:~na~ ,Meeting i(!!!ftlile Am e~ica!r:l :As150d~liion fllli!' the .t!:chtanl1ement o:fS,tiie'noe. !iSdience ,glnd 1~(;J1m liIolo:gy ifi~lm a G'lobalIP~r.elj_ive!! empilaJsizE:!1S the pOlNer',of sci:ellce ;andletnflO~o:gy i9iS,wetl as Mucatiollill to asslst lessdeve.~o,pe(J1segwnent:s ofUe 'iI'Iroii~ds,ocT:ety. to 1m prOV\e par~!1ieirshilPiS amomilg a ~~ll!idi¥"d'e\lleh)lped cQuntnies,.a.nd! to spuw :know~.edge·drivel1 tr,amlfClIlrrm:diolrrlS ,:lC1ross i3J host.oHie:ldls.. As yO!!!, kl!1ow.the AAAS A~lfI\I!al Mee:bl!ii1lg has becoflile the most, ~mrpotrtalii!lt ga1ti~.eri~ig of~~le year ror ti~te,gJ()1,!jing segme DiIIt of :stiel'drl~1!:S;3Jfid Eillli1lgilrlJE!!E!rrs s.El.el m 'E!'Jilplolrli! the '1j!jI.1110 inite:rsed.h:ms bet,wee,~, discrplil'lieS endto wib'!e.ss t,he bm'illdinl\lluelt'Q,ce of s,01Ie!'!ce and techn(ll[logy Oil w,dety, '1I'Qillil 'W',ill h~\fe Ute I~PPQ:nJiiPtlity ~@; imer,~e~ wi~~ii:diVerse!lrray of tea~:ingsciemriSts,! elilginee'rs~ !edw!aroo:rs,. st n:ldel1lltst iilnd 'poUcy"makler:.s.. Attenci'!re8,YlliU have the ,opp~ril:urlility t~ clilloose: amo:li1lg ;3i broafJll'il!lilIe of,a.ctiM~i\!l5, indlU]ring ::160 sym:pos~a" :s@imillal':s,. and ,c:aUrEl ell' di,evelojJ m@<l1t wQ,rkshops as ~~mas, p~,@na!y a:lfildtOIP'ical laeturss by SCIllTleonhewowldl',!; leadingSCie:lllltist5 O3IliiIdlill~·Ii1I:eN3ms. e 'fYIP~c;allY'the meeting im::lud1es up t'O 10,'000 p!SIl'tHcilJantsi1l:nd hundirilllOS ofmne:mbeifS ofthe' lliiatiollal and inrerrllli1Jrtioli1lal 'medh:ll.
r

iIiIl'nethe Iliru~for ~'hle mee~lli1lrg -

Sipedal Events IIFlclude~

'. Marine Sdel1lces, S,emil:ilar ,~ ~brum
mill SCh{)10Q
1

s,G:iel1!£:e INutritirofl

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I. Topical
'I

'. fli~!tl'narytactu res Lecttllll['El5

A pl!lblh>enga~m~nt e:v~liiliton ''''Wnders,t,andilillg Obe:sUy and (iI1IlI.dho~d ~Iutfitio~;'; is, in!l:eml,deG WI expand the dial[,o,gue ,arnO'mlI8: s·cientists,. te:aelher5. stu de If!Its. polkY'rmak'€lfS, edtJlcatiolj'j ~,@ade;~:s"aifil the g:e:n'!l! al ;pl!i.ilblk Oil the :sdenO~' behind dilUdhoo d obeS!l tv €lInd d r nutri tilO'Iil, ~t wiU 'featu:!ie a bu:oad and excit:ing'array 'of speakers W:~tha strOl1gfooUl:S on :s:tr:a.tegi'E!s for i3Jddn!!s:Silrlg thep[ioblem.~()u snd you~ f'a'lIrii~V can i311~s.o @n~oy FamitY'Sdli!n~e:!' ~)!a!ls - a fre~ Ie;VE:iflit open to tlm:ElGElneil'a~ pl.iIl:J!~ic. i1ihefolLowiili'lg pl3lgll!!:s prrese:l1Iit:the lillligMSlhil:S oflhe :sdentifk pl!,ogtilrm to d'i'lf:e. YOl!! e'xplore 't,he p:!lGgr,arn Ql'dij~ie',Q'btain l!Update:~ ant! dlevelop;;l pe:rSQl1al itilnJe~.ry at .www.aaas.(lrg/meetings,.
(i3J11ii

'. P;o:sterSes5,ioWiS

flIImMy Sde:m::',e Da;ys

(,a f,ee if Ex.tr,a s:

'. Si:i'ell'lce Ca.reters f~i'r
'I

'iliirneAnWltNd M'eetilrn:g: reIi[JB()t$, trel11lemh;n[:I5 eff.ort5 ~'rr(!!m the AAAS S'E!cttons .•dh/isklns. and comm~lLiIt@e's, w lim icWil.W@glr<lJtefuny03;ck:l1ow]edge .. I <lI~SO '~tr@nd a pe:rsona!~ thiilb to the me!inbel~s of ~hle Al!lln ~al Medlili!,g s.c iemtitUk Progrrai!ir! Com m~·t:te,e wt! 0 lreviewed a!I!lQd a.ssembledl the Ima:IrlY exoo Ih1lllillit ideas a ndprcpos als inil:Othis ,outSt!lllliding fill eetilllg.

SJP,et~a ~jl@,d Ciare@:r Works!l1olPs

rarF'el1!r 1I!J@'50UOC,e'e,nlb~!r (

I Dynillmic

~:o_~
Plea~ joil1 us in IBoston. O:aV']d Ba~~lmo~e.Ph.D, AMS !P,res-idlenl
Rober~ Arldrews Mi~IUk<il:1iII1 rornSSiQrf P Calfiifo rnia II'lS'tHl!Ji'e' of iedlillillolo gy on~h)'logy

PI!tJl'llS, i11rs. _DJIlIIII~

~ U!illc

fl!!Jt!S.orl~t~m'!g[ioI:~~ 0!',1'IIl;~[iIIi!lI O!JIUlfiI:!if er Ll!i~

Atte nd plenary and toptcal lectures given

by eminent sclentlsts and eng'inee rs.

,Global HerJlth ChaU,e'rJ'ges

MAS 'res~ij]ent li>avrnd IB:alt~mOrrre·,. moderato:r
DiireL.lol". FI1aIm1r~:is.xiJ.~!i'!f lEIagl'lolJ!U!lICemr~eli'oow ,l1CeiiJUba.nd HllIlfll<lilll Riigrli\lts. Harvard, ,S(=':oolra'f II\IlbUc Hea~iI1l, ilml.ifJI lPifooossm o~f :Social Me,~lieiifile and ,M.edii:t:ii!l,e,.11,llalMro M.edi1iml~5(jlilool rGl1'IIiilMd) ExeC:liJltlve IDii'i~UCli". UNA.IDS,~IId1 Under S.e.r:reta:ry·G,eneliirll
liJl'liit:edi N<!Jtil01'l!i

Plenary teeture Panel

. I]a l"i;;,

IfI II,'U,I,,'

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,.;;;J!'

Hm'tong Kim ,M.D.!. Ph.D,

l

Oa.yid Bal~imore, Ph.ID"

MAS Pl'esidelm~:: RObert Andirews MiiUika 11 ,PIITl5!fes8or ~f IEli'O'~rlD'gy., Ca.6foli1lliia 1~lIlst:itu~e of
Te(;hlill!ll!ogy

Peter P'wot~M.D., Ph.D.

of the

:Baltimore ":sone ofthe w{uld'$ ~!eadjili1~lbioh:~gi:sts. aJ!ilJd aCJ]·~edpieVi!lt or the' 1975 Nobel IPI~b:ei!1 Medicij~,e' fo!" the dr.S('OVtery ()h~eil'S,e tmlllscriptas.e .•Sillce then. he has piUliblishe-dl I'IH)'['@' ~h>afl 600 Ipaperrs" i,fI!ClUd~iliilrg se'M]l'Iat research onthe g@'~le[ics of cancer, ~l1ieWOM:]rlgs. of nIle' HIV vln~sa m1id DS V(lrI:::cil1E! ,All ca.ndlidate s" and 'flurd:amellita~, (lbservatioll:5 hal mo~e;cull3Jl" immlJlml:ology, He' woo ful!Jm~m1li d'jire'ctlClr oH~e White!hel1ld Institute roirr l!J:iomredka!l Res,el!:m::h and p~es]dE'!ililiti)f!~()Ckrefunelr IJiI:d\i\er:;;.lty a'lili,d I Calte<:h, Toda.y he meads ~&1te' Baltim'Olrie il~b at Caltech,. wJ~hSil.llpp(lrt fromtlhe Gates iFou!'!dalio~ffi!I; 00 1001<:fur wa!~~o gel'!et~,ca!~IV'beest the immll!mle systl€ml against irnf€dtou:s pathiogePils, pa:rtJkular~y H~V; Throughout 'hiis (anee~ Bal.ib1l11'lol'eas ilnnue:lilc:ed s(ijencrl/l [piQrlicy" He h Ilelped set standards for mtombirlarrt IDNA.ile dhll1llology and r¥loeived the 1999 Natioll'!ral. Medal of:5ciience· ~'1iI1par'~for hils wOlrik on AIDS research pdlk:y:. Todlay he :j15Oi!JtSIP<Olke!'l about wtflat he sees as gOlVerffi!l1ileli!it.e:m)lrts to· distort aliDd slUJpp.ress sdemiitific reseaJfCh. Preslde'r~'Il':sRece.,ptlM: 'mmed]ate/ffo~~'(}w!.f1.g

N ina V~fedor"llff, Ph.[)<.

SIPecial Ad'fwsefjSdience and re!l:liIlil!!llo~ U~S ..lih~p Ilt!UfIemil: 'of:smlf:!' a EVaIIili Pogh lP,roFesStIll ofBiol~'gy 'i!I.rKI :Will;~l1Ilililll1ll 'Pm\@!f~\5ol" rI))If llI.iufe: Sdel!1:~s.ltill!Ju;k Iinstiitut~ 'on1n.r~: ILit: SdrenCleli. Pe~n5yl¥~ulila .$ita.t.e I!JniYlI]!isity'

AMS liP'r,eskle1iliit :a!~tiimOlre 'wi II moder~te a DaJVQs," e s1y1e pi1!ilt'le I di.scl.! S~iO'!iii' thQlt e.xph~!r:e$ glob~I.Ih,e.a~l~~1 C:1TIr,alleng.es 'from ~"e~ peif'spe'cti'll~s.~ :philiant!lilio'p1t, w'Orld Itealirersihlip,. and pmgrnm successss ,il'i 00 olhliSl.ll.engrf!ls .. EX.reoll:litiIV.e:dilrlliCMr"Or UINAIII)S since Us (~reatiOilll!l ill 1995 and I!lIlllider .M!Cll!itary":g.E!IlE!'ril I. of the Ullliitedl Na.tioIl1lIS, Pio~ {DIme's· from a distinguished ,~cadeimk tll'ldi ~c~eli!itil'iccareer focus~~' ornAllrIJSal!'ld~l(')ime!'l's he,a!lth in i~h:e de:VE:itopirng 'world. Dl:alwing en his$!k~lIs as a s'CleUliltist,. MiaJlillagiE!f, nd au1:vist·, !liE!has c:h3ilh~li:!I.g€d a IHOrld ~ei3.dI,ersr(l, vnew A~ID'S~ifl Qonil1!xt or sodal. tile 13111.([1 etonomk dewiopl'1ll@nt as wen as s.ewwil)t KilFflI has wOIli~e d 00,im pmlJ.ie healillhin d'E!v,f! 10j:lililg OOrlJnt)rie5 for mQme than 20 'Y81;!lrS anoiSSfi lexpert in ~~lbel'W~g'5is. Hei$.;;1 fo'~nd~!m~tJruste.e andl the fOMiller exewtiw d'ire-dor ofPa:nne.rs II'IDI! Hea~thi a flot·fu r·pm~:~ ,ofgaililizaUon thi3!t Stl,PPQII'ts a ra l!iI.ge of IIir,ea~[t'~1 program 5, ~1Ti1 poon:omfl1l'~ niti~s frn Hi3Iijiti, Pel'l!.l" R.ur5:sia, Rwanrla, 8:11(1the United Sta:mes. A lJallLen~t wm be adld!e·dIDo, offier a lP'erspE!!ctive011 providilr1:g sl~ppciu~~o cl(llmbat d~seases ;;;Ind OO'ii!ddl~SS otn.e'r g:lobal health~orlICerlru;.

In' the ,{)e.v~iopl{J'g Wo.n'd . ~rnAu g;!J.Ist:2>007. Fedoro~r"'!i'as liIamed th:e Scie:nee and '"fee hno~og'l{ M~islew00 U.S. SeCirr~tifl.1}of Stine GQndo~eelEtiI.IRIi(e..S.he holldlsilin , a:c:adem~~ic as the Ewn IP'lLIghProfesoolr ·Qf .Buol.og:y and Wi~l<ln1i3in iPrQS~ P,rofes·:soroUJfe Sdenoesat: IPennS!yilva~lia~t,at:E! UliliiVJefsl'ty. wj~e·re S she il~ :also i\u.llGllidil'lgdiulI;ct~rof ~hle Huck ~Uilsti~lWltes f ~I:n,e fe o U $c!€ilii!c:es. As a lea.di"g gef!e:t~CI1:sta~d m:ole:Gutar bijo'log]s<t~ :she has contJrlb!!JJtedto, the dewllorpMent: of modi em ttE:d~liiI!iql,ljrlilS l!JJisedto st!ll.idvand modify pl6iill!ts., Her book. Mellde:iltJ the' Kitc.hen: A S(i'efJtis~'s'View of (j'!M:etlc,aUr MOdified foods,. exam Ilme·sthe s(;~entiliirc a !;rId societal iSSllIleS5.tII rrlro'l!]nd~mr,g ttl1reilrmoductiOrl (If sene:1tlica~ly' modifiedl ~1!UpS.She ~ecll;1iV',edhe 2000 National Med~1 t @W' Sden~e IF()lr el~ piQ!ille elliil!1g woriC on !p,la~'~mol~eov,rllarbi (l\o.gy' .al1d h fO!!i.bei~g tihe finrt 'to dO!ii!e ii!i!il!d(h;;l!~acterb::e OiIaize' tJraml,S\poSOrtlis.

Making' the I~rid fkJh Science ~nd T~hflOlQgy