%PDF-1.3 % 94 0 obj <> endobj xref 94 20 0000000016 00000 n 0000001206 00000 n 0000001287 00000 n 0000001431 00000 n 0000001549 00000 n 0000002240 00000 n 0000002761 00000 n 0000002864 00000 n 0000010161 00000 n 0000010684 00000 n 0000011103 00000 n 0000011275 00000 n 0000011647 00000 n 0000011923 00000 n 0000012078 00000 n 0000018107 00000 n 0000022814 00000 n 0000025115 00000 n 0000026012 00000 n 0000000696 00000 n trailer <<2F947EEB2AC9BE4587D19C047B806410>]>> startxref 0 %%EOF 113 0 obj <>stream xb```"Nu'!b`e`s%-q iW\~Kx؋}a>{,b 3N33_h& g`?cϗC_0kj endstream endobj 95 0 obj <> endobj 96 0 obj <> endobj 97 0 obj <>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 98 0 obj <> endobj 99 0 obj <> endobj 100 0 obj <> endobj 101 0 obj <>stream /GS1 gs BT /F1 1 Tf 17.9328 0 0 17.9328 138.5007 646.4124 Tm 0 0 0 rg 0 Tc 0 Tw [(Simultaneous)-336.7(Reconstruction)-337(of)-333.6(Multiple)]TJ -.6133 -1.2235 TD [(Signaling)-334.2(Pathways)-333.6(via)-336.9(the)-333.7(Prize-Collecting)]TJ 4.3216 -1.2203 TD [(Steiner)-336.2(Forest)-334.6(Problem)]TJ 9.9626 0 0 9.9626 128.6929 558.8786 Tm [(NURC)-9(AN)-333.8(TUN)-10(CBAG)-9(,)]TJ 7.4718 0 0 6.641 221.9527 563.3007 Tm (1)Tj 9.9626 0 0 9.9626 229.0393 558.8786 Tm [(ALFRED)-10.3(O)-334.8(BRAU)-9(NSTEI)-8.6(N,)]TJ 7.4718 0 0 6.641 342.7086 563.3007 Tm (2,3)Tj 9.9626 0 0 9.9626 355.4078 558.8786 Tm [(ANDREA)-343.5(PAGN)-8.4(ANI,)]TJ 7.4718 0 0 6.641 446.2298 563.3007 Tm (3)Tj 9.9626 0 0 9.9626 122.9669 546.9164 Tm [(SHAO)-8.4(-SHAN)-341.2(CARO)-9(L)-336.3(HUANG,)]TJ 7.4718 0 0 6.641 256.4787 551.3384 Tm (1)Tj 9.9626 0 0 9.9626 263.5086 546.9164 Tm [(JE)-8.2(NNIFER)-342.5(CHAYES,)]TJ 7.4718 0 0 6.641 353.9338 551.3384 Tm (4)Tj 9.9626 0 0 9.9626 361.0204 546.9164 Tm [(CHRISTI)-10.3(AN)-333.8(BOR)-10(GS,)]TJ 7.4718 0 0 6.641 451.8991 551.3384 Tm (4)Tj 9.9626 0 0 9.9626 172.9133 534.9542 Tm [(RICCARD)-11.3(O)-334.7(ZECCH)-11.1(INA,)]TJ 7.4718 0 0 6.641 279.4393 539.3762 Tm (2,3)Tj 9.9626 0 0 9.9626 292.0818 534.9542 Tm [(and)-339.8(ERNEST)-341.9(FRAEN)-9.7(KEL)]TJ 7.4718 0 0 6.641 402.0093 539.3762 Tm (1)Tj /F2 1 Tf 10.959 0 0 10.959 259.5968 480.4156 Tm (ABSTRACT)Tj -16.9266 -2.3641 TD [(Signaling)-237.9(and)-237.7(regulatory)-236.9(networks)-235.6(are)-240.7(essential)-237.9(for)-240.9(cells)-238.6(to)-237.9(control)-240.5(processes)-236.7(such)-236.8(as)-237.6(growth,)]TJ 0 -1.1795 TD [(differentiation,)-323.9(and)-320.4(response)-325.3(to)-320.6(stimuli.)-321.8(Although)-321.3(many)-320.6()43.3(omic)47.3()-324(data)-324(sources)-323.8(are)-323.5(available)]TJ 0 -1.1847 TD [(to)-579.3(probe)-569.7(signaling)-575.6(pathways,)-567.7(these)-577.8(data)-572.3(are)-577(typically)-572.2(sparse)-574.2(and)-573.9(noisy.)-573.9(Thus,)-574.8(it)-570.7(has)]TJ 0 -1.1795 TD [(been)-412.7(difcult)-404.1(to)-408.6(use)-411.1(these)-412.3(data)-406.7(to)-408.6(discover)-408.9(the)-406.2(cause)-410.8(of)-408.6(the)-411.4(diseases)-404.8(and)-408.4(to)-408.6(propose)-409(new)]TJ T* [(therapeutic)-406.4(strategies.)-404.8(We)-405(overcome)-405.6(these)-401.9(problems)-405.4(and)-403.2(use)-405.9()48.5(omic)47.3()-406.8(data)-406.7(to)-403.4(reconstruct)]TJ 0 -1.1847 TD [(simultaneously)-493.2(multiple)-495.8(pathways)-496.9(that)-496.1(are)-494.2(altered)-500.4(in)-496.5(a)-493.2(particular)-497(condition)-497.5(by)-494.8(solving)]TJ 0 -1.1795 TD [(the)-457.9(prize-collecting)-459.6(Steiner)-453.6(forest)-462.4(problem.)-452.5(To)-458.4(evaluate)-454.4(this)-456.2(approach,)-454.2(we)-459.4(use)-457.7(the)-457.9(well-)]TJ 0 -1.1847 TD [(characterized)-272.9(yeast)-266.4(pheromone)-265.6(response.)-266.7(We)-265.3(then)-268.1(apply)-268.9(the)-266.5(method)-264.6(to)-268.9(human)-265(glioblastoma)]TJ 0 -1.1795 TD [(data,)-462(searching)-462.1(for)-463.4(a)-462.2(forest)-462.4(of)-460.3(trees,)-463.9(each)-459.5(of)-465.5(which)-460.8(is)-461.8(rooted)-459.4(in)-460.3(a)-462.2(different)-465.3(cell-surface)]TJ 0 -1.1847 TD [(receptor.)-418.6(This)-418.1(approach)-414.5(discovers)-417(both)-411.6(overlapping)-413(and)-418.7(independent)-413.2(signaling)-415.2(pathways)]TJ 0 -1.1795 TD [(that)-361.6(are)-354.5(enriched)-361.8(in)-356.8(functionally)-356.1(and)-356.6(clinically)-354.8(relevant)-357.4(proteins,)-360.5(which)-357.4(could)-358.1(provide)-357.8(the)]TJ 0 -1.1847 TD [(basis)-431.9(for)-432.3(new)-435.1(therapeutic)-427.1(strategies.)-435.9(Although)-424.8(the)-437.2(algorithm)-428.9(was)-430.1(not)-430.8(provided)-431.7(with)-428.4(any)]TJ 0 -1.1795 TD [(information)-340.6(about)-341(the)-338.9(phosphorylation)-338.3(status)-341.8(of)-341.3(receptors,)-344(it)-337.9(identies)-344.8(a)-338.1(small)-342.8(set)-345.6(of)-341.3(clini-)]TJ 0 -1.1847 TD [(cally)-334.5(relevant)-331.5(receptors)-335.3(among)-327.6(hundreds)-332.4(present)-334.1(in)-331(the)-333.8(interactome.)]TJ 0 -2.359 TD [(Key)-294.7(words:)]TJ /F1 1 Tf 5.2456 0 TD [(multiple)-295.1(network)-290.5(reconstruction,)-285(prize-collecting)-295.1(Steiner)-288.8(forest,)-290.4(signaling)-292.9(pathways.)]TJ /F2 1 Tf 9.7825 -3.9316 TD [(1.)-501.9(INTRODUC)5.6(TION)]TJ 27.7155 0 0 27.7155 74.0976 181.4173 Tm (H)Tj /F3 1 Tf 9.9626 0 0 9.9626 96.7748 193.2661 Tm [(igh-t)-7.6(hroug)-7.6(hput)-328.8(techn)-9.1(ologies)]TJ /F1 1 Tf 14.0215 0 TD [(includin)-10.5(g)-325.1(mass)-329.4(spectro)-9.2(metry)-8.2(,)-324.7(chromati)-9.3(n)-325.1(immu)-7.2(noprecip)-8.7(itation)-331.2(fol-)]TJ -14.0215 -1.2007 TD [(lowed)-194.4(by)-183.6(seque)-8.6(ncing)-190.5(\(CHIP-Se)-9.5(q\),)-186(RNA)-191.3(sequen)-9.3(cing)-184(\(RNA)-11.9(-seq\),)-187.5(and)-186.2(micro)-8.2(array)-193.4(and)-186.2(screeni)-10.9(ng)-183.6(methods)]TJ -2.2762 -1.2007 TD [(have)-279.8(the)-280(pote)-7.6(ntial)-275.6(to)-277.4(provide)-285(dramatical)-11.5(ly)-277.4(new)-275.5(insight)-9.1(s)-275.1(into)-276(biologi)-7.9(cal)-276.1(proce)-9.4(sses.)-281.9(By)-273.7(provi)-8.6(ding)-273.3(a)-281.4(relatively)]TJ T* [(com)-7.6(prehensi)-9.9(ve)-367.5(view)-364.3(of)-367.7(the)-365.3(change)-9.9(s)-366.2(that)-363.2(o)-6.5(ccur)-367.1(for)-364.7(a)-366.7(specic)-372.4(type)-366.1(of)-367.7(molecu)-8.7(le)-364.6(or)-367.7(perturbation,)-372.5(thes)-8.8(e)-361.1(ap-)]TJ T* [(proac)-9.4(hes)-215.8(can)-216.4(uncove)-8.1(r)-207.6(previ)-10.3(ously)-212.6(unrec)-9.4(ognized)-216.5(proce)-9.4(sses)-213.3(in)-214.8(a)-213.1(system)-219.9(of)-214.1(interest.)-220.7(Howeve)-10.3(r,)-208(interp)-8.2(reting)-218.7(these)]TJ T* [(data)-191.5(type)-7.6(s)-184.1(toge)-7.6(ther)-186(to)-186.4(provi)-8.6(de)-185.4(a)-190.3(coherent)-192.6(view)-193.6(of)-185.6(the)-188.9(biological)-193(proce)-9.4(sses)-190.5(is)-187.6(still)-186.8(a)-190.3(challengin)-9.9(g)-182.9(tas)-8(k.)-183.2(In)-191.3(order)-186(to)]TJ ET q 1 i 74.098 113.953 m 504.51 113.953 l 504.51 69.902 l 74.098 69.902 l W n 0 0 0 RG 1 J 1 j .454 w 10 M []0 d q 1 0 0 1 74.098 113.953 cm 0 0 m 490.677 0 l S Q Q BT 6.7246 0 0 5.9768 84.0755 103.8047 Tm (1)Tj 8.9663 0 0 8.9663 87.4771 99.7795 Tm [(Department)-336(of)-330.4(Biological)-336.9(Engineering,)-335.3(Massachusetts)-339.3(Institute)-334(of)-336.7(Technology,)-335.5(Cambridge,)-334.4(MA.)]TJ 6.7246 0 0 5.9768 84.0755 93.8268 Tm (2)Tj 8.9663 0 0 8.9663 87.4771 89.8583 Tm [(Department)-336(of)-330.4(Applied)-339.1(Science,)-334.2(Politecnico)-339(di)-331.8(Torino,)-335.2(Torino,)-328.9(Italy.)]TJ 6.7246 0 0 5.9768 84.0755 83.8488 Tm (3)Tj 8.9663 0 0 8.9663 87.4771 79.8803 Tm [(Human)-329.3(Genetics)-338.3(Foundation,)-335.9(Torino,)-335.2(Italy.)]TJ 6.7246 0 0 5.9768 84.0755 73.8708 Tm (4)Tj 8.9663 0 0 8.9663 87.4771 69.9023 Tm [(Microsoft)-335.6(Research)-336.7(New)-336.3(England,)-334.5(Cambridge,)-334.4(MA.)]TJ /F2 1 Tf -1.4922 74.5218 TD [(JOURNAL)-340.5(OF)-331.2(COMPUTATIONAL)-337.8(BIOLOGY)]TJ 0 -1.2203 TD [(Volume)-336.3(20,)-337.1(Number)-333.3(2,)-331.2(2013)]TJ /F4 1 Tf 0 -1.2266 TD (#)Tj /F2 1 Tf 1.3341 0 TD [(Mary)-337.5(Ann)-334.1(Liebert,)-332.8(Inc.)]TJ -1.3341 -1.2203 TD [(Pp.)-335.5(124136)]TJ T* [(DOI:)-337.5(10.1089/cmb.2012.0092)]TJ 9.9626 0 0 9.9626 281.8204 34.9228 Tm (124)Tj ET endstream endobj 102 0 obj <> endobj 103 0 obj <> endobj 104 0 obj <> endobj 105 0 obj <> endobj 106 0 obj <> endobj 107 0 obj <> endobj 108 0 obj <>stream htWwTT-v%FŎb"I`: eR v&{/y&1)ww[gǙ=}ovCۿ{ZAI>[}c{VG\AWGS ţ c /LJI]> 2m3lon.[ 11Y..QQ.[l .[į£\\\A.1!.c`.fĻKH<0S;aQv-dΝkg=n1ڮڧk?uТAEz|`p?Y1$jQʓj:! "wf:9 Z7>fû|t,C{LbpRw^]ސod_2]Pxs"qљLmGָCZAt=iEK30րkh0X d}q0V840Lo   sf3"`36*]ʹv]\0h6kx5g ( :lu~cas> G*R]88of 7SVH`&`UGe}Kf>Wp iNKU̅/pP-χֻ~\Kb&fcatp:.F;tv;X}$oo rk`eL>%)@O+p֡M_EuW}(oj+vOyR.#:Vbbc \XLç0gZ*83&no++tއ c̈́t?a5PD3&ѵ l5Rӛӧ˪ taM߂^Rcq1N(d`zzpgL-| deVJB  Iڭ)3 *03=*LP!^d M4 $$zU8?юmU]|-1ʻ,l"jjiba+W-d&s}Ll{wk8[,zEƎ?C9+xmYӸrqM5mm]4 Pa5P/fKR.W -d1g:@0p2PdInio>_ZVg k[ ]&) /5d]k"eJna`-{$Ueaϋlp{#m28B8ct ^B< ke; ,ցU:ܷܗRXXG4 mk_u dSw."c =2}I 8Y]HR {ftef>bq!a//CQ.g}n\c\ENoO7'r~K m6wba(t:_ 0 j]ylwsYP~"[U[,dq~ ;dg|L~4]qjtYmU J}7wV?jS> nܲ9?pRC:\ZU˷x?Ϸo[H,0[nK5qP@2j3:Q 4 ҀvWKvjlHP)fאb=Y>%rxv@ ٜ਌7Lh~@p?Lu=B4'Th]0њ@Xx3 GβA N_s*ȋhNkL裌Y( uz} %bD}E:q|%Sd㦄$'#g@^1I٭ܝB ťok-H(vۖ 3_cje XgkM w:tdy*$J#?˂({| x~ٿAc řv00.I3_8j`##>u^ {'x G;KR)&e ;D5e@Q˿t]?&I$װK+eVR] aL R3Wr )R\9Wm qu)S$pTy*iRm68Ytb]AC䐘Ϊ j)qO9QiHOwU5I?OBjYL'9Y|bltj4u]w=ɩEsD2L~gF N%8٬YPҍں,)s§󓠄R:c7hkrG=~BeJC^ WTRwLZQev!AUfs1~1D#RnY5hl+!)I,RspvM=QSV 8)TYS9af2s"g۵&_UdlcWq,9--'ftU*m6/k>Y5[h9*I\׽4EIĪ0IKUk2Sma FQk>̔YiRG(=ܡ׋RI搪<h:V@|ߗOhs#=:y8N7PvSKQ9iN_DèjRQ~x-S!mX l z|L7br/kio O+ܩW)FLܐ\#:_9GVc`Ć| ^Q4א 5 150\դ_Sha|[^-&L<, 0TTƌ`&3m_6 fҨTn[އy .rʪ k֡JX#M||vg[?XpW/ɆpFfcnigqx{R-ACрݫis%|Qt:Qco׎m endstream endobj 109 0 obj <>stream hޔWiT׶nCڱ VVE&D#F(" 8 4v3C ĨQc3\5ܘ]yUoֽZjsN}>N"a"'' ޫz"/r͕W'"j0*V #92u*A +"2Z*SG(BUQ2wT40lҰaa? _=\9TgsxxUTd1A.]nX2"qĭȪ0jʨQ0:|t_xi@2Z(ÌQiwZ^7n\и'jOgK:g\[Nmf-f8;?e'CKҴI8I]@G Ml9q;a.!zo?$pT 6QGS8H&_a͞M8ų8Ơ8&:hpq㧠VzFNMBЂNRz¸KiQ.&V͏"^PdU3)x戁''- 16_}q_"LJ/++8~>\֪cWwH#K!q8ݨxPu[% \u5}~|!6ofx9p4$)JwC)x NSmܺEs-.~j/( ГA pa],ѹcdM/\ NK^Ӯ%L&젩Z:P r~;mOBFݯ?glB;K'jV!kl y h9wCu ట@S=pkloq#g؏,b驸1JZ3in/\<\n1PSe*b̕ Glëת6ⶸT67?V*] LuK\-qaC b56z!-?Q7*)T(7NV.wt0էY*e%oԲ*EQ'A;}: 0o3,orn0ߗ~QPd84Gp[Ovna%k&+@!,^SQӆ=xG_Y劥%Uܞ_a` ӀAF,I{\܅>0B:LWw8`KxYEu{6ٓłIs1 #$')?n*Krł3^3-}+TݺHgMa/HoЭA`d;`O,mdMAW\T8m55rkJ=k *j@wİq#!pSo0KHChd W3 mj`Zpu`m⽅W>\?SYtyFntU䴮7JE#F)@ a ޣ `O°~G=f噊tϾP&\τʩrSQ}|~(ʃlsv(>&4> g@:`˯# rF'i5xXoE.6<"8&)''6Eƈayf-} tX {asY`+i'&J23dAXHC"C8gJŗp|4t!/*rO\_K$pmޛ<8b`a!BƝ|TmmMz cWMiKBg؈%z# M?v>F}H>6jEIB O5~CߧzKT䋼}> ^2_&HUQ_{ǐJ!(?yh L\ !L;Au͸1^Py  0 ڨI/&jzDŽGϪ,UQݛgd!{ 6H|,??ЭsYS!pR`<fI0:>k1 ,%koԧk5,plN#W@C(%I$iiq1;._4d\q7ףϪ1¡:aNdc0.k={)xieA/PjU$Kœ%?$Of8IeYOJyr\WCYVE8/ p.֕ʘvǪB%;}p?umSHcC|^HtVFho4qnui./PVKl8 kP_1Ei)4K9(Pw0Zfj Zi@/kEOggz}No-⠒|f@eEcn8q垭Jn!8!l 욢zU%=sh3}tjz\\ǖ 'ZNl¢`g$k##S8(-]_Zu[_wO@BSWhX?R/@v|V՘l~䊱pճ[8gN~Շ-qzNx7N"aH)cU=? $$sEhڙT@00Ɓkvi071h,ma\Qd`ߵo7Eư7s}iEcEh `?*/_͕!n<ȁ%!;Xh59[lOEjX5YIE!Rɋ%Z'=e^$T/̭oeM&dG>2GXK0CȻ;ێvuʏ u9Ҹ/єLeq"NGMz;8:72d%;u]B3I##.KHbRta:Jr5l@]cŞ ']I3g~pڮLV)XISΕ.N 详Zt@5V^4*9y׸5ʡT1zn9Gϟ>w1016Fo79DP]jsC-? '=DgG}l2p×i5~+O\:sG.EWgxi.ǀkkIGޞ1p"x_ g۝Wdwvvo#q$f.ȬMNW}{$\FkE`p7:vm(ƵF=^'z]fr7)zQ$DnߚX%ۨE%e)I_ẅimnlY]: e!gRz-.S`*tqGuL# 3wou 1HM $*B&4%aжnfI[ T`LpMvL5e?lb2tivz.]cA!ptbtcy\Qa46R04[a0j2D1[qT2@% ꘺zsY@PX`,J< eۀR4Z͕*5iZ40>Jz'7P?`Wp7iڌVFqN}Vdz5y8^K3Rd ۚt>|xYzAwD+$ȳBMOwmA7q#Ng0҄*~[Gt)P;ÿB[k6߾Ur24+;t֡<0ABPȹ|G=.Hగct/>stream htT}XTesߗ\,ڽӢ@&! 1H jK, 0 _sG`D2q>$ $%55Kɥ%6+cs=ٽcOm>y?P1FRRZPdR~ez悤t1>A95]bt 켵kMT;<ɆҚr}F6|mt종Q7ci h3kb6dPg*ȟ&mެ#ƂJwyZSy^~Aq^&a6U_b0ՔhiJ5kJq>_W/0i J1F0&,`y*fy0Yf2u*F3 S uPScfsvH/bMǂn<,{Th;E5`+IQcQ{sLxMh(XaCqśux>0؋/H#/{X[ލuyw8 ][ 8cD smvoqx ,&7*Lsw I+T)LM [jT3)4*V "KiՒU9`0v[3f]_ pG om[!27XH. O+>E M9anS$c(3X0x9̀`d7vOtzDZzIJuV6QIU)az0c "b0ͨ0 Y5J?zj,=%٭;:_l7>y#$85EtHq;;B C1 UjQ˼$uf|GyHr?˒N}z}F k բ a!vCI+ ?}uD5.f3v0X}4bvM҄Y/՞MV<g_QDpWYxҺQNA`0÷#8 [SR)5ڥg{p*`(C^XfJ!=}WĽ2ԲBʒ%'}T#~`^TwMJVJNF |;99FYh/ hο-:VckImKX?05ydpDN " !h--FGtuNaqpvX'm.< hB|$@R},?1UzP\5y  ֮$@Gh]_kNU|5rv ]Y;^!?gB{%Top|bLi*!iUNvE/:0CI*I8(X)~[_Cb:~s8gsxblB ,S1) ` .7 !.dEtPn'*``[EcU-ؚݪmy3z썪2Ks?2.qˌMيcfakF0¦Oz4U3sD,'Jp{'۴(mh0>9#[Nߛ%ܗ(=P׌KsҞAmOcn߶۹k|V8K\L^Q]ʒo_m`LޤvmNwH.SxҀSX9r&K"S-=T4tô?#zrnt˸5t~!j N`mw@3`;2%2uT[j(Qlm_cOvu~>stream h,Rˎ4n5g3K$l҈ 6M'Ny?} ??ᓧ=]W7G~Lg;."'r"Ͻ^vXk\{wFRGBL霂Yl,F1ڡd}՗x6`dN}H ؉C1Xs5*wƴx`J&Y`)P:oAɇ|(UneHQԢP IJdԇ"UBjϣE^)N4'F8,A~x3LqON~xݝ닸N=g3'6ґn-%\g]-IX%`n6w2`9 ԩl$v& 4 Q`ga#d!dt{!4#`0)jH3L %`ЌVL.-NaWgKKV[k5׳ڹEay\uXYн3Cm"!: 48%̣sanPcy[ hB=nٟ1Xv|De-XƷkq.^Wg5nQP }^UjfgPϢ-rÓ}2ŻLr JR]KrNh8Xƒ`7ExNa53>D_j=ݍ endstream endobj 112 0 obj <> endobj 1 0 obj <> endobj 2 0 obj <>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 3 0 obj <>stream /GS1 gs BT /F1 1 Tf 9.9626 0 0 9.9626 107.6031 715.4644 Tm 0 0 0 rg 0 Tc 0 Tw [(discover)-214.8(h)-6.5(o)0(w)-210.3(change)-9.9(s)-206.8(i)0(n)-209.2(dif)-7(ferent)-214(classes)-216.2(of)-214.1(molecu)-8.7(les)-212.9(relate)-216.6(to)-209.2(each)-213.3(othe)-7.6(r,)-208(it)-211.9(is)-210.3(possibl)-7.6(e)-207.4(t)0(o)-214.8(map)-212.5(the)-211.7(data)-214.2(onto)]TJ 0 -1.195 TD [(a)-213.1(networ)-9.3(k)-211.3(o)0(f)-214.1(known)-218.3(or)-208.4(predi)-10.3(cted)-214.2(intera)-10(ctions.)-218.3(Ideally,)-216(the)-217.4(observed)-217.7(int)-7.8(eractions)-220.1(would)-215.4(all)-214.5(lay)-217.4(near)-219.2(each)-213.3(othe)-7.6(r)]TJ 0 -1.2007 TD [(in)-260.4(a)-258.6(functi)-8.2(onally)-262.3(coher)-9.4(ent)-257.2(part)-265.6(of)-259.6(the)-262.9(interact)-10.3(ion)-261.1(network)-266.2(\(the)-260(intera)-10(ctome\).)-267.2(Howeve)-10.3(r,)-259.2(due)-260.2(to)-260.4(false)-263.7(posi)-7(tives)]TJ T* [(and)-277.2(false)-280.8(negativ)-8.7(es)-277.7(in)-271.7(both)-279(the)-274.3()48.5(om)-7.8(ic)48.1()-275.9(data)-276.8(and)-277.2(the)-280(interactome)-12.2(,)-273.5(the)-280(true)-277(situatio)-8.7(n)-273.9(i)0(s)-272.9(muc)-7.6(h)-273.9(more)-277.8(com)-7.6(plex;)]TJ T* [(advanc)-9.9(ed)-225.2(algorithm)-11.1(s)-223.9(are)-229.8(needed)-231.9(to)-220.5(n)-6.4(d)-222.7(meanin)-8.7(gful)-229.7(connections)-231(amo)-7.6(ng)-223.5(the)-228.8(data.)-231.7(Among)-227.5(the)-228.8(appro)-7.6(aches)-226.6(that)]TJ T* [(have)-194.4(been)-200.1(propos)-7.7(ed)-191.1(to)-197.8(nd)-195(these)-193.4(subnet)-10.3(works)-198.7(from)-192.6(the)-194.6(int)-7.8(eractome)-203.6(are)-195.6(network)-197.9(ow)-198.9(optimiza)-10.1(tion)-190.7(\(Lan)-200.1(et)-193.9(al.,)]TJ T* [(2011;)-399.2(Yeger-)-10.3(Lotem)-398.7(et)-398.7(al.,)-399.5(2009\),)-398.8(network)-402.8(propagat)-8.7(ion)-397.7(\(Vanunu)-400(et)-398.7(al.,)-399.5(2010\),)-398.8(the)-399.5(Steiner)-402.6(tree)-398.3(appro)-7.6(ach)]TJ T* [(\(Bailly-Bec)-12.6(het)-416.6(et)-410.1(al.,)-410.9(2010a;)-418.8(Dittrich)-417.5(et)-410.1(al.,)-416.6(2008;)-410.6(Hua)-8(ng)-411.2(and)-413.8(Fraenkel)-9.7(,)-410.1(2009\),)-410.2(networ)-9.3(k)-410.5(infere)-9.2(nce)-409.9(from)]TJ T* [(gene)-319.6(expre)-9.4(ssion)-316.2(\(Bai)-8.6(lly-Bech)-10.5(et)-313.4(et)-319.1(al.,)-319.8(2010b;)-320.3(Friedm)-8.2(an,)-316.7(2004\),)-319.2(linear)-322.9(program)-8.9(ming)-316.6(\(Ourf)-8(ali)-316.9(et)-319.1(al.,)-319.8(2007\),)]TJ 0 -1.195 TD [(maximum)-9.1(-likeli)-8.8(hood)-247.7(\(Yeang)-253.1(et)-250.8(al.,)-245.8(200)-8(4\),)-242.9(ele)-8.6(ctric)-248.2(circui)-10(ts)-244.5(\(K)-7.4(im)-246.8(et)-245.1(al.,)-251.5(2011;)-251.3(Missi)-8(uro)-249(et)-245.1(al.,)-251.5(2009;)-251.3(Suthram)]TJ 0 -1.2007 TD [(et)-279.2(al.,)-285.7(2008\),)-285(networ)-9.3(k)-279.6(alignm)-9.7(ent)-280(\(Shar)-8.8(an)-282.2(and)-282.9(Ideker,)-285.6(2006\),)-285(and)-288.6(Bayesian)-287.6(networ)-9.3(ks)-281.6(\(Akavi)-9.3(a)-281.4(e)0(t)-279.2(al.,)-285.7(2010\).)]TJ 1.0015 -1.2007 TD [(In)-453.1(our)-453.8(previous)-457.7(wor)-8.2(k,)-450.7(we)-456.8(used)-455.6(the)-456.4(prize-)-9.2(collecting)-462.2(Steiner)-459.5(tree)-455.2(formal)-10.9(ism)-453.6(to)-453.8(nd)-451.1(an)-458.6(optimum)-456.1(tree)]TJ -1.0015 -1.2007 TD [(composed)-327.4(of)-322.2(nodes)-325.5(dete)-9.4(cted)-322.4(in)-323(experim)-11.5(ents)-321.8(\(termin)-8.7(als\))-323.7(and)-322.8(nodes)-325.5(that)-323.3(wer)-10(e)-321.2(not)-318(d)-6.5(etected)-325.3(\(Ste)-8.8(iner)-322.6(nodes\).)]TJ T* [(We)-335.9(assigned)-344.9(costs)-335.1(to)-334.3(each)-338.5(intera)-10(ction)-335.5(reec)-10.4(ting)-332.9(our)-340(conden)-8.1(ce)-335.2(that)-334.7(the)-336.9(repor)-9.6(ted)-331.2(intera)-10(ction)-335.5(was)-339.2(real)-341.4(and)]TJ T* [(assigned)-344.9(prizes)-338.4(for)-336.3(excl)-9.4(uding)-336.6(any)-339.8(of)-333.6(the)-336.9(terminal)-12.1(s)-332(from)-340.6(the)-336.9(tree)-341.4(based)-338.6(on)-337.3(conden)-8.1(ce)-335.2(in)-340(the)-336.9(proteom)-9.7(ic)-336.1(or)]TJ T* [(transcrip)-9.7(tional)-253.6(d)-6.5(ata.)-253.7(By)-250.9(minimi)-8.5(zing)-252.3(the)-257.2(sum)-251.7(of)-253.9(the)-257.2(total)-252.9(cost)-253.5(of)-253.9(all)-254.3(edges)-259(in)-249(the)-257.2(tree)-256.1(and)-254.5(the)-251.5(total)-258.6(prize)-256.8(of)-253.9(all)]TJ T* [(nodes)-257.2(not)-261.1(contained)-262.4(in)-254.7(the)-257.2(tree,)-262.1(we)-257.6(were)-257.2(able)-259.8(to)-254.7(obta)-7.6(in)-254.7(comp)-8.4(act)-253.3(and)-260.2(biologi)-7.9(cally)-257.6(relevan)-9.7(t)-253.9(networ)-9.3(ks)-253.1(\(Bai)-8.6(lly-)]TJ 0 -1.195 TD [(Bechet)-455.6(et)-449.9(al.,)-450.7(2010a;)-447.3(Hua)-8(ng)-445.4(and)-453.6(Fraenkel)-9.7(,)-444.2(2009\).)-455.7(Despite)-452(the)-450.7(powe)-8.8(r)-446.6(o)0(f)-447.4(the)-450.7(Steiner)-453.8(tree)-449.5(appro)-7.6(ach)-449.7(for)]TJ 0 -1.2007 TD [(identifyi)-10.3(ng)-263.3(functi)-8.2(onally)-273.7(coherent)-272.3(networ)-9.3(ks,)-264.9(it)-268.8(is)-267.3(restricted)-276.8(to)-266.1(discover)-9.9(ing)-266.8(a)-270(connecte)-10.3(d)-262.5(subgr)-7(aph,)-266.2(whi)-9(ch)-265.1(may)]TJ T* [(be)-413(an)-418.7(inad)-7.6(equate)-416.7(repr)-8.8(esentatio)-10.3(n)-416.2(for)-416(many)-418.1(systems.)-421.4(In)-413.2(p)-6.5(articular,)-423.2(we)-417(often)-420.1(expect)-422.4(there)-416.2(to)-419.7(be)-413(man)-7.6(y)-410.5(si-)]TJ T* [(multaneous)-10.1(ly)-311.6(acting)-315.3(biologi)-7.9(cal)-315.9(processe)-10.1(s)-309.2(i)0(n)-311.6(the)-308.4(cel)-8.6(l)-305.1(that)-317.7(may)-309.2(n)-6.5(o)0(t)-305.9(b)0(e)-316.3(connecte)-10.3(d)-308.1(togethe)-8.7(r)-310(b)0(y)-308.8(intera)-10(ctions)-314.7(in)]TJ T* [(the)-359.7(current)-9.9(ly)-357.1(know)-7(n)-353.6(intera)-10(ctome.)-361.2(Th)-7(ese)-359.9(processe)-10.1(s)-354.8(may)-360.4(b)-6.5(e)-355.4(unconne)-8.9(cted)-362.2(either)-362.8(becau)-9.2(se)-357.3(they)-360.4(may)-360.4(invol)-9.3(ve)]TJ T* [(essential)-11.5(ly)-334.3(independe)-9.3(nt)-334.3(cell)-342.2(functions,)-342.1(or)-333.6(simply)-339.2(due)-334.1(to)-334.3(ou)-7.2(r)-332.8(imperfec)-10.3(t)-333.6(knowled)-8.1(ge)-333.4(of)-339.2(the)-336.9(interactome)-12.2(.)]TJ 1.0015 -1.2007 TD [(In)-350.6(this)-351.2(wor)-8.2(k,)-348.3(we)-354.4(formul)-9.1(ate)-350.1(a)-355.4(forest)-355.7(\(dene)-9.3(d)-347.9(a)0(s)-357.3(a)-349.7(disjoint)-359.8(union)-353.7(of)-350.6(trees\))-357.5(appro)-7.6(ach)-353(to)-351.4(identi)-9(fy)-350.6(simulta)-8.7(-)]TJ -1.0015 -1.2007 TD [(neously)-358.2(acting)-360.8(pathwa)-9.1(ys)-349.8(in)-357.1(biologi)-7.9(cal)-355.7(networks)-359.2(usin)-7(g)-347.9(b)0(o)-7.2(t)0(h)-351.4(proteom)-9.7(ic)-353.2(and)-356.9(transcrip)-9.7(tional)-356.1(data.)-356.9(We)-358.7(use)-358.1(a)]TJ 0 -1.195 TD [(general)-9.7(ization)-449.7(of)-447.4(the)-445(mes)-8.8(sage-pas)-10.1(sing)-445.2(algo)-7.6(rithm)-447.3(for)-450.1(the)-445(Prize-c)-10.9(ollecti)-8.6(ng)-445.4(Steiner)-453.8(Tree)-446.6(\(PC)-8.2(ST\))-447.2(problem)]TJ 0 -1.2007 TD [(\(Bailly-Bec)-12.6(het)-348.3(et)-341.8(al.,)-342.6(20)-7.2(10a;)-343.3(Bayat)-9.2(i)-339.3(e)0(t)-347.5(al.,)-342.6(2008\).)-347.6(We)-347.3(rst)-343.9(demonst)-8.9(rate)-347.1(the)-342.6(forest)-350(approach)-349.2(by)-343(usin)-7(g)-342.2(i)0(t)-342.8(t)0(o)]TJ T* [(integr)-8.2(ate)-452.5(proteom)-9.7(ic)-455.6(and)-453.6(transcrip)-9.7(tional)-458.5(data)-453.2(in)-453.8(the)-456.4(yeast)-455.2(phero)-7.6(mone)-457.9(response,)-458.3(show)-8.2(ing)-454.6(that)-454.2(the)-456.4(forest)]TJ T* [(consist)-9.3(s)-360.5(o)0(f)-362(trees)-371.8(enriche)-9.7(d)-359.3(i)0(n)-362.8(speci)-11.3(c)-361.1(and)-368.3(distinct)-367.2(biologi)-7.9(cal)-361.4(proce)-9.4(sses.)-367.3(As)-365.2(an)-361.8(addi)-7.6(tional)-367.5(featur)-9.2(e,)-361.4(direct)-10(ed)]TJ T* [(edges)-8.6(,)-319.1(which)-331(are)-326.5(partic)-10(ularly)-326.8(usef)-8(ul)-323(for)-324.9(represe)-10.1(nting)-328(the)-325.5(effects)-331.6(of)-327.9(enzymes)-328.4(and)-328.4(transcr)-11.1(iptional)-326.2(regul)-10.3(ators)]TJ T* [(on)-331.6(their)-343.2(targets,)-342.3(are)-332.2(als)-8(o)-330.8(inco)-7.6(rporated.)]TJ 1.0015 -1.2007 TD [(We)-284.7(reas)-9.8(oned)-289.4(that)-283.5(the)-291.4(Steiner)-294.5(forest)-287.4(appro)-7.6(ach)-290.4(could)-287.2(be)-287.8(utilize)-8.6(d)-285.3(i)0(n)-283.1(mode)-8.4(ling)-287.4(mammal)-10.1(ian)-285.7(sign)-7(aling)-284.3(whe)-8(re)]TJ -1.0015 -1.2007 TD [(there)-279.6(are)-281(many)-275.8(mor)-7.8(e)-275.7(cell-surface)-286.8(rece)-10.4(ptors)-277.2(and)-277.2(down)-7(stream)-279.4(path)-7.6(ways)-277.4(than)-280.8(in)-277.4(yeast.)-279.2(In)-276.7(princi)-8.2(ple,)-274.7(the)-280(forest)]TJ 0 -1.195 TD [(appro)-7.6(ach)-392.8(could)-395.3(uncove)-8.1(r)-389.7(multipl)-8.5(e,)-389.9(independe)-9.3(nt)-391.3(com)-7.6(ponents)-398(of)-390.5(the)-393.8(biological)-397.8(resp)-8(onse.)-393.4(Altho)-7.6(ugh)-389.2(the)-393.8(in-)]TJ 0 -1.2007 TD [(teractom)-11.1(e)-344(data)-350.8(are)-349.3(much)-349.8(less)-351.4(comple)-8.7(te)-341.8(for)-347.7(mamm)-9.7(als)-349.5(than)-349(for)-347.7(yeast,)-347.5(we)-348.7(show)-349.6(that)-351.8(the)-348.3(same)-347.1(metho)-11.9(ds)-344.2(are)]TJ T* [(applica)-10.5(ble.)-382.8(We)-387.1(built)-382(pri)-7(ze-collec)-11.9(ting)-384.2(Steiner)-385.5(fore)-8.8(sts)-383(derived)-389.2(from)-386.1(proteom)-9.7(ic)-381.7(data)-385(from)-386.1(a)-383.8(model)-387.5(of)-384.8(glio-)]TJ T* [(blastoma)-281.7(multiform)-9.1(e)-270(\(GBM)-9.9(\))-270.2(i)0(n)-271.7(which)-274.1(each)-275.9(tree)-278.8(was)-271(root)-7.8(ed)-270.8(in)-271.7(a)-270(dif)-7(ferent)-276.6(cell)-273.9(surface)-277.6(rece)-10.4(ptor)-269.6(repr)-8.8(esenting)]TJ T* [(independe)-9.3(nt)-482.3(sign)-7(aling)-489.1(pathway)-9.9(s)-480(and)-487.8(potential)-488.1(point)-9.3(s)-480(o)0(f)-487.2(therapeu)-10.5(tic)-481.9(interv)-8.2(ention.)-490.3(The)-481.9(solu)-7(tion)-486.6(reveals)]TJ T* [(several)-471.9(known)-468.7(pathwa)-9.2(ys)-463.7(and)-465(some)-464.8(unexpe)-8.1(cted)-470.3(new)-463.3(ones)-467(that)-471.3(are)-463.1(alter)-9.2(ed)-464.2(in)-459.5(the)-467.8(disease)-471.1(and)-465(sugges)-8.8(ts)]TJ T* [(potential)-362.9(ther)-9.6(apeutic)-363.3(strategi)-9.7(es.)-357.7(The)-362.4(modied)-365.4(algorithm)-363.9(can)-358.7(n)-6.5(o)0(w)-358.3(b)0(e)-356.1(appl)-7.6(ied)-359.7(to)-357.1(a)-355.4(wide)-364.3(range)-362.2(of)-356.3(com)-7.6(plex)]TJ T* [(system)-9.3(s.)]TJ /F2 1 Tf 10.959 0 0 10.959 287.9432 201.4299 Tm [(2.)-501.9(METHODS)]TJ /F5 1 Tf -16.4559 -1.6399 TD [(2.1.)-496.9(Datasets)]TJ /F1 1 Tf 9.9626 0 0 9.9626 117.5811 165.5433 Tm [(Through)-7.1(out)-301(this)-305.7(work,)-305.2(two)-304.9(differ)-9.4(ent)-302.7(biological)-312.5(networks)-308(are)-303.7(used:)-305.5(the)-308.4(yeast)-307.2(interact)-10.3(ome)-303.5(and)-305.7(the)-302.7(human)]TJ -1.0015 -1.2007 TD [(interact)-10.3(ome.)-338(We)-335.9(refer)-337.7(to)-334.3(nod)-8(es)-334.6(with)-336.9(prize)-336.5(valu)-7.6(es)-334.6(grea)-8.6(ter)-333.2(than)-337.7(zero)-338.7(as)-334.6(termin)-11.7(al)-330.4(nod)-8(es.)]TJ /F5 1 Tf 10.959 0 0 10.959 117.5811 129.7133 Tm [(2.1.1.)-497(Yeast)-261.2(dataset.)]TJ /F1 1 Tf 9.9626 0 0 9.9626 218.7212 129.7133 Tm [(The)-260(yeast)-267.4(intera)-10(ctome)-264.1(cont)-7.6(ains)-264.9(34,712)-266(protei)-8.2(nprotein)-266.5(and)-265.8(transcrip)-9.7(tion)-264.7(factor)-9.2(s)]TJ -11.1535 -1.2007 TD [(to)-351.4(target)-357.1(intera)-10(ctions)-354.5(betwee)-10.9(n)-353.6(5,957)-356.2(nodes.)-354.3(The)-356.7(terminal)-359.2(node)-357.7(set)-355.2(contain)-8.7(s)-349.1(106)-355.1(different)-10.5(ially)-355.3(phospho)-6.5(ry-)]TJ T* [(lated)-303.1(protei)-8.2(ns)-298.6(detect)-9.8(ed)-299.2(by)-303.1(mass)-301(spectro)-9.1(metry)-304.1(\(Gruhl)-9.5(er)-301.2(et)-296.3(al.,)-302.7(2005\))-307.4(and)-300(118)-298.2(d)-6.5(ifferentiall)-11.5(y)-296.7(expre)-9.4(ssed)-303.1(genes)]TJ T* [(\(Issel-Tar)-12.7(ver)-336.1(et)-330.4(al.,)-336.9(2002\))-335.8(detect)-9.8(ed)-333.4(by)-331.6(micro)-8.2(array)-335.7(in)-334.3(response)-338.4(to)-334.3(the)-336.9(mating)-339.8(pheromon)-7.7(e)-332.6(alpha)-334.5(factor)-9.2(.)-330.4(T)0(h)-7(e)]TJ T* [(node)-266.6(prizes)-264.5(are)-269.6(compute)-9.5(d)-262.5(from)-260.9(the)-268.6(fold)-263.9(change)-9.9(s)-258(betwee)-10.9(n)-262.5(treated)-268.6(and)-265.8(nontreat)-11.5(ed)-259.4(condi)-8.4(tions.)-267(The)-265.7(edge)-262.7(cost)-8.8(s)]TJ T* [(are)-252.5(calculat)-10.1(ed)-248(by)-251.9(taking)-250.9(a)-247.2(negativ)-8.7(e)-247.2(log)-249.7(of)-248.2(the)-251.5(intera)-10(ction)-250.1(proba)-7.6(bility.)-249.3(Th)-7(e)-247.3(details)-251.7(are)-252.5(availa)-9.8(ble)-251.5(in)-249(Huang)-248.5(and)]TJ /F2 1 Tf 0 67.0005 TD [(SIMUL)-9.7(TANE)-9(OUS)-339(RECONST)-12.2(RUCTI)-10.1(ON)-333.3(OF)-340.6(MULTI)-9.5(PLE)-335.9(SIGNA)-9.9(LING)-10248(125)]TJ ET endstream endobj 4 0 obj <> endobj 5 0 obj <>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 6 0 obj <>stream /GS1 gs BT /F1 1 Tf 9.9626 0 0 9.9626 74.0976 715.4644 Tm 0 0 0 rg 0 Tc 0 Tw [(Fraen)-8.6(kel)-274.3(\(2009\).)-276.4(In)-271(this)-277.2(study,)-269.9(we)-274.7(modi)-9.3(ed)-270.8(the)-274.3(transcrip)-9.7(tion)-276(factorDNA)-280.1(intera)-10(ctions)-274.8(to)-271.8(be)-270.8(d)-6.5(irected)-274.3(edges)-8.6(.)]TJ 0 -1.195 TD [(We)-455.4(also)-452.7(added)-456.9(to)-448.2(the)-456.4(interact)-10.3(ome)-451.5(a)-452.1(set)-451.9(of)-447.4(dir)-7(ected)-455.8(edges)-452.4(that)-454.2(represe)-10.2(nt)-448.2(phospho)-6.5(ryl)-7(ation)-455(and)-447.9(dephos)-7.6(-)]TJ 0 -1.2007 TD [(ph)-7.2(orylation)-269.3(reacti)-11.7(ons)-265.2(betwee)-10.9(n)-262.5(kina)-7.6(ses,)-268.6(phosphata)-8.7(ses,)-268.6(and)-265.8(their)-269.2(subst)-9(rates)-269.4(\(Breit)-9.2(kreutz)-269(et)-267.8(al.,)-268.6(2010\).)-267.9(If)-267.2(these)]TJ T* [(int)-7.8(eractions)-351(are)-349.3(available)-352.3(in)-345.7(the)-348.3(original)-348.2(intera)-10(ctome,)-349.8(proba)-7.6(bilities)-347.3(are)-349.3(retained.)-355.1(If)-341.2(they)-349(are)-349.3(not,)-346.9(the)-342.6(prob-)]TJ T* [(abili)-8.2(ties)-324.5(of)-327.9(these)-330(interact)-10.3(ions)-325.7(are)-326.5(set)-326.7(uniform)-9.9(ly)-323(to)-323(0.8,)-326.6(based)-332.9(on)-325.9(the)-325.5(distributio)-8.3(n)-325.1(o)0(f)-322.2(the)-325.5(p)-6.5(robabilitie)-10.7(s)-320.6(i)0(n)-328.7(the)]TJ T* [(ori)-7(ginal)-301.3(interact)-10.3(ome.)-298.2(The)-299.8(nal)-302.7(interact)-10.3(ome)-297.8(cont)-7.6(ains)-299(35,998)-300.1(edges)-304.5(betwee)-10.9(n)-296.7(5,957)-299.3(nodes.)-303.1(In)-299.4(both)-296(case)-9.6(s,)-298.2(the)]TJ T* [(resu)-8(lting)-336.5(intera)-10(ctomes)-340(are)-337.9(comprised)-344.2(of)-333.6(both)-335.9(undirect)-11.5(ed)-333.4(and)-334.1(dir)-7(ected)-336.3(edges)-8.6(.)]TJ /F5 1 Tf 10.959 0 0 10.959 84.0755 619.8235 Tm [(2.1.2.)-497(Human)-245.5(dataset.)]TJ /F1 1 Tf 9.9626 0 0 9.9626 193.4362 619.8235 Tm [(Prot)-7(einprot)-9.7(ein)-240.2(intera)-10(ctions)-246.4(in)-243.3(the)-240.2(STRI)-8.8(NG)-242.7(data)-9.4(base)-241.1(\(ver)-8.8(sion)-240.3(8.3)-7.6(\))-236.1(are)-246.8(used)-245(as)]TJ -11.9786 -1.195 TD [(the)-325.5(data)-322.4(source)-324.3(for)-319.2(the)-319.8(huma)-8.4(n)-319.4(interactome)-330.9(\()-122.2(Jense)-9.8(n)-319.4(e)0(t)-319.1(al.,)-319.8(2009\).)-324.8(Here,)-320.2(the)-325.5(probabiliti)-8.9(es)-317.5(from)-323.5(exper)-9.4(iments)]TJ 0 -1.2007 TD [(and)-254.5(data)-9.4(base)-252.5(evid)-7.6(ence)-253.1(channe)-9.9(ls)-250.2(are)-252.5(com)-7.6(bined)-253.1(to)-254.7(obtain)-256.6(the)-251.5(nal)-257.2(probability)-256.5(of)-253.9(the)-251.5(intera)-10(ctions.)-252.5(Int)-7(eractions)]TJ T* [(wi)-8.2(th)-328.7(a)-326.9(combine)-9.5(d)-325.1(proba)-7.6(bility)-334.3(greater)-336.1(than)-332(0.8)-326.3(are)-332.2(include)-8.7(d)-325.1(i)0(n)-334.3(the)-325.5(int)-7.8(eractome.)-334.9(Th)-7(e)-326.9(recepto)-9.7(r)-327.1(molecu)-8.7(les)-332.4(are)]TJ T* [(collec)-9.8(ted)-262.9(from)-266.6(the)-268.6(Human)-263.4(Plas)-8(ma)-262.9(Mem)-9.6(brane)-265.4(Databa)-10.9(se)-260.6(\(Ben-)-8.6(Shlomo)-266.2(et)-262.2(al.,)-268.6(2003\),)-262.2(whe)-8(re)-261.4(331)-264.1(rece)-10.4(ptors)-265.8(are)]TJ T* [(avai)-9.4(lable)-320.2(in)-317.3(the)-319.8(interact)-10.3(ome)-314.9(d)-6.5(erived)-320.2(from)-317.8(STRI)-8.8(NG.)-317.1(Th)-7(e)-315.5(phospho)-6.5(proteom)-9.7(ic)-313.4(d)-6.5(ata)-315.9(in)-317.3(Hua)-8(ng)-314.5(et)-319.1(al.)-319.4(\(2007\))-321.5(is)]TJ T* [(com)-7.6(bined)-372.6(with)-371(the)-371(huma)-8.4(n)-365(intera)-10(ctome)-372.2(for)-370.4(the)-371(GBM)-377.1(test)-370.1(case.)-374.2(From)-372(this)-374(dataset,)-376.3(72)-365.7(prot)-7.8(eins)-367.3(cont)-7.6(aining)]TJ T* [(ph)-7.2(ophorylated)-343.8(tyrosine)-340.9(peptide)-8.7(s)-332(are)-337.9(present)-339.2(in)-334.3(our)-340(human)-339.2(interact)-10.3(ome.)]TJ /F5 1 Tf 10.959 0 0 10.959 74.0976 511.4833 Tm -.0001 Tc [(2.2.)-502.1(Prize-collecting)-334.8(Steiner)-330.3(tree)-333.5(problem)]TJ /F1 1 Tf 9.9626 0 0 9.9626 84.0755 493.5684 Tm 0 Tc [(For)-350.6(a)-349.7(give)-7.6(n,)-348.3(directed)-354.7(or)-350.6(undirect)-11.5(ed)-350.4(network)]TJ /F5 1 Tf 18.3748 0 TD [(G\(V,)-349.8(E,)-348.1(c\(e\))-10.6(,)-347.5(p\(v\)\))]TJ /F1 1 Tf 7.944 0 TD [(of)-350.6(node)-352(set)]TJ /F5 1 Tf 4.9451 0 TD (V)Tj /F1 1 Tf .9617 0 TD [(and)-351.2(edge)-353.8(set)]TJ /F5 1 Tf 5.5141 0 TD (E)Tj /F1 1 Tf .6146 0 TD [(,)-347.5(where)-354.7(a)]TJ /F5 1 Tf -39.3558 -1.2007 TD (p\(v\))Tj /F6 1 Tf 1.9519 0 TD ()Tj /F5 1 Tf .8877 0 TD (0)Tj /F1 1 Tf .7341 0 TD [(assigns)-241.1(a)-235.9(prize)-239.7(to)-237.6(each)-236(node)]TJ /F5 1 Tf 11.3356 0 TD (v)Tj /F6 1 Tf .6146 0 TD ()Tj /F5 1 Tf .8763 0 TD (V)Tj /F1 1 Tf .6203 0 TD [(,)-233.7(and)]TJ /F5 1 Tf 2.1681 0 TD (c\(e\))Tj /F6 1 Tf 1.895 0 TD ()Tj /F5 1 Tf .8877 0 TD (0)Tj /F1 1 Tf .7341 0 TD [(assign)-11.5(s)-229.6(a)-235.9(cost)-236.4(to)-237.6(each)-241.7(edge)-234.2(e)]TJ /F6 1 Tf 11.5063 0 TD ()Tj /F1 1 Tf .8763 0 TD [(E.)-234.3(The)-237.2(aim)-238(is)-233.1(to)-237.6(nd)]TJ -35.0879 -1.2007 TD [(a)-338.3(tree)]TJ /F5 1 Tf 2.629 0 TD (T\(V)Tj 7.4718 0 0 6.641 115.2567 467.9999 Tm (T)Tj 9.9626 0 0 9.9626 119.3952 469.644 Tm (,E)Tj 7.4718 0 0 6.641 128.0126 467.9999 Tm (T)Tj 9.9626 0 0 9.9626 132.1511 469.644 Tm (\))Tj /F1 1 Tf .3357 0 TD [(,)-330.4(b)-6.5(y)-330.8(minimi)-8.5(zing)-337.7(the)-336.9(objective)-339.2(funct)-10.3(ion:)]TJ /F5 1 Tf 9.9755 -2.1169 TD (f)Tj /F7 1 Tf .4268 0 TD (\()Tj /F5 1 Tf .3244 0 TD (T)Tj /F7 1 Tf .6317 0 TD (\))Tj /F6 1 Tf .4894 0 TD (=)Tj /F8 1 Tf .7227 0 TD (b)Tj /F9 1 Tf .7568 .9503 TD (X)Tj /F5 1 Tf 6.9738 0 0 6.9738 267.8739 437.2156 Tm (v)Tj /F10 1 Tf .4552 0 TD (=)Tj /F11 1 Tf -.0894 0 TD (2)Tj /F5 1 Tf .6585 0 TD (V)Tj 4.9813 0 0 4.9813 279.3259 436.1385 Tm (T)Tj 9.9626 0 0 9.9626 284.655 448.5542 Tm (p)Tj /F7 1 Tf .5008 0 TD (\()Tj /F5 1 Tf .3244 0 TD (v)Tj /F7 1 Tf .4496 0 TD (\))Tj /F6 1 Tf .4894 0 TD (+)Tj /F9 1 Tf .9503 .9503 TD (X)Tj /F5 1 Tf 6.9738 0 0 6.9738 311.0739 437.9526 Tm (e)Tj /F11 1 Tf .4471 0 TD (2)Tj /F5 1 Tf .6585 0 TD (E)Tj 4.9813 0 0 4.9813 323.0361 436.8755 Tm (T)Tj 9.9626 0 0 9.9626 328.3653 448.5542 Tm (c)Tj /F7 1 Tf .4496 0 TD (\()Tj /F5 1 Tf .3244 0 TD (e)Tj /F7 1 Tf .4496 0 TD 14.9856 Tc (\)\()Tj /F1 1 Tf 15.6319 0 TD 0 Tc (1)Tj /F7 1 Tf .5008 0 TD (\))Tj /F1 1 Tf -42.8783 -3.0558 TD [(whe)-8(re)-289.8(the)-291.4(rst)-292.7(term)-291.9(is)]TJ /F8 1 Tf 9.1959 0 TD (b)Tj /F1 1 Tf .8365 0 TD [(time)-8.2(s)-286.5(the)-291.4(sum)-291.5(of)-288(the)-291.4(node)-295.1(prizes)-292.9(not)-289.6(include)-8.7(d)-285.3(i)0(n)-288.8(the)-291.4(tree)]TJ /F5 1 Tf 23.2288 0 TD (T)Tj /F1 1 Tf .552 0 TD [(,)-290.6(and)-288.6(the)-291.4(secon)-8.6(d)-285.3(part)-294.1(is)]TJ -33.8132 -1.2007 TD [(the)-336.9(sum)-337.1(of)-339.2(the)-336.9(edge)-336.7(costs)-335.1(o)-6.5(f)]TJ /F5 1 Tf 12.0412 0 TD (T)Tj /F1 1 Tf .552 0 TD [(.)-330.4(Not)-9(e)-332.6(that)]TJ /F9 1 Tf 3.2607 -1.1723 TD (X)Tj /F5 1 Tf 6.9738 0 0 6.9738 231.6472 373.7196 Tm (v)Tj /F10 1 Tf .4471 0 TD (=)Tj /F11 1 Tf -.0813 0 TD (2)Tj /F5 1 Tf .6585 0 TD (V)Tj 4.9813 0 0 4.9813 243.0424 372.6424 Tm (T)Tj 9.9626 0 0 9.9626 248.3716 385.0582 Tm (p)Tj /F7 1 Tf .5008 0 TD (\()Tj /F5 1 Tf .3244 0 TD (v)Tj /F7 1 Tf .4496 0 TD (\))Tj /F6 1 Tf .4894 0 TD .3357 Tc (=-)Tj /F9 1 Tf 1.8437 .9446 TD 0 Tc (X)Tj /F5 1 Tf 6.9738 0 0 6.9738 283.6346 374.3999 Tm (v)Tj /F11 1 Tf .4471 0 TD (2)Tj /F5 1 Tf .6585 0 TD (V)Tj 4.9813 0 0 4.9813 295.5968 373.3794 Tm (T)Tj 9.9626 0 0 9.9626 300.9259 385.0582 Tm (p)Tj /F7 1 Tf .5008 0 TD (\()Tj /F5 1 Tf .3244 0 TD (v)Tj /F7 1 Tf .4496 0 TD (\))Tj /F6 1 Tf .4894 0 TD (+)Tj /F5 1 Tf .7227 0 TD (const)Tj /F7 1 Tf 16.7985 0 TD (\()Tj /F1 1 Tf .3244 0 TD (2)Tj /F7 1 Tf .5008 0 TD (\))Tj /F1 1 Tf -42.8783 -3.0558 TD [(so)-270.2(that)-266.4(minimizi)-8.9(ng)]TJ /F5 1 Tf 7.8359 0 TD (f\(T\))Tj /F1 1 Tf 1.7641 0 TD [(amo)-7.6(unts)-263.1(to)-266.1(collec)-9.8(ting)-264.7(the)-268.6(largest)-268(set)-269.8(of)-265.3(high)-261.9(p)-6.5(rize)-267.4(vertices)-270.5(while)-271.1(minimizi)-8.9(ng)-263.3(the)-268.6(set)]TJ -9.6 -1.2007 TD [(of)-242.5(large)-245.4(cost)-247.8(edges)-241.9(in)-243.3(a)-241.6(trade-)-9.2(off)-239.6(tune)-7.6(d)-239.8(b)0(y)]TJ /F8 1 Tf 16.8952 0 TD (b)Tj /F1 1 Tf .552 0 TD [(.)-239.4(A)0(s)-245.7(a)-241.6(starting)-247(point,)-243(we)-246.2(consider)-248.9(the)-240.2(mes)-8.8(sage-pas)-10.1(sing)-240.3(algo)-7.6(rithm)]TJ -17.4472 -1.2007 TD [(for)-290.8(the)-285.7(PCST)-284.8(probl)-8.6(em)-285.7(introdu)-7.1(ced)-284.7(in)-283.1(Ba)-8(illy-Beche)-10.9(t)-282.4(e)0(t)-284.9(al.)-285.3(\(2010a)-8.3(\).)-282(Th)-7(e)-281.4(message)-10.9(-pas)-8(sing)-285.8(algorithm)-289.9(conver)-10.1(ts)]TJ T* [(the)-348.3(global)-347.6(problem)-345.4(of)-344.9(nding)-342.3(the)-348.3(optimal)-343.3(tre)-8.8(e)-338.3(into)-344.3(a)-344(set)-343.8(of)-339.2(loca)-9.4(l)-339.3(problem)-9.7(s)-337.7(that)-346.1(can)-347.3(be)-344.8(solved)-346.1(efcientl)-10.3(y.)]TJ T* [(Th)-7(ese)-274.5(equat)-10.1(ions)-274.5(are)-281(solved)-277.8(itera)-9.2(tively)-276.4(in)-277.4(a)-275.7(computa)-9.5(tionally)-280.7(efcient)-285.6(way.)-275.8(Here)-280(we)-280.4(present)-282.3(a)-275.7(general)-9.7(ization)]TJ T* [(of)-259.6(the)-257.2(message)-10.9(-passin)-8.6(g)-251.2(algo)-7.6(rithm)-259.5(designed)-264(to)-254.7(solve)-259.9(the)-257.2(PCST)-262.1(problem)-260.1(on)-257.6(directed)-263.7(networks)-262.4([)]TJ /F5 1 Tf 37.7283 0 TD (i.e.)Tj /F1 1 Tf 1.2292 0 TD [(,)-256.5(where,)-258.4(in)]TJ -38.9575 -1.2007 TD [(gener)-9.4(al,)-461.7(c\(e{i,j)-8.6(}\))-457(mig)-8.6(ht)-459.5(be)-458.6(differ)-9.4(ent)-462.1(from)-460.1(c\(e{j)-10.4(,i}\)].)-458.3(In)-464.4(this)-459.3(variant)-10.7(,)-455.6(the)-462.1(op)-7.2(timization)-466.7(will)-464.8(be)-458.6(done)-465.8(on)]TJ 0 -1.195 TD [(dir)-7(ected)-393.2(rooted)-392.4(trees,)-395(where)-394.6(choice)-394(of)-390.5(the)-388.1(root)-389.1(\(w)-7.4(hich)-388.9(will)-390.8(be)-390.3(part)-390.8(of)-390.5(the)-388.1(candidat)-11.3(e)-389.5(tree\))-389.7(is)-392.4(an)-390.3(external)]TJ 0 -1.2007 TD [(para)-8.6(meter)-340(of)-333.6(the)-336.9(algo)-7.6(rithm.)]TJ /F5 1 Tf 10.959 0 0 10.959 74.0976 235.0488 Tm -.0001 Tc [(2.3.)-502.1(Prize-collecting)-334.8(Steiner)-330.3(forest)-333.6(problem)]TJ /F1 1 Tf 9.9626 0 0 9.9626 84.0755 217.1338 Tm 0 Tc [(A)-255.1(type)-258(of)-253.9(pri)-7(ze-collec)-11.9(ting)-253.3(Stei)-9.6(ner)-256.4(forest)-259(\(PCSF)-8.2(\))-253.1(has)-255.6(already)-260.1(been)-262.7(consider)-9.9(ed)-253.7(in)-254.7(Chekuri)-261.3(et)-256.5(al.)-256.8(\(2010\))-258.9(and)]TJ -1.0015 -1.2007 TD [(Gupt)-9.7(a)-258.6(e)0(t)-262.1(al.)-256.8(\(2007\))-8.5(.)-256.5(I)0(n)-259.6(thes)-8.8(e)-258.6(works,)-261.7(penal)-10.1(ties)-261.9(are)-263.9(assigned)-265.2(to)-260.4(each)-264.5(pair)-260(of)-265.3(nodes)-262.9(either)-266(directly)-264.6(connec)-9.9(ted)-257.2(in)]TJ T* [(the)-388.1(tree)-386.9(\()]TJ /F5 1 Tf 3.8468 0 TD (i.e.)Tj /F1 1 Tf 1.2292 0 TD [(,)-381.6(edges)-389.8(belongin)-7.7(g)-382(t)0(o)-379.9(the)-388.1(forest)-8.6(\))-378.3(o)0(r)-384.8(comple)-8.7(tely)-385.9(disconnec)-10.5(ted)-382.4(\()]TJ /F5 1 Tf 25.5164 0 TD (i.e.)Tj /F1 1 Tf 1.2292 0 TD [(,)-387.3(i)0(n)-379.9(differ)-9.4(ent)-382.4(forest)-389.8(compo-)]TJ -31.8216 -1.2007 TD [(nent)-7.6(s\).)-249.8(Her)-10(e)-252.9(w)0(e)-251.9(consider)-260.3(a)-252.9(different)-260.9(PCSF)-255.8(construc)-9.9(tion)-253.3(for)-250.9(a)-252.9(give)-7.6(n,)-251.5(directed,)-258.3(or)-253.9(undirect)-11.5(ed)-248(n)-6.5(etwork)]TJ /F5 1 Tf 40.1639 0 TD [(G\(V)-8(,)-250.8(E)0(,)]TJ -40.1639 -1.2007 TD [(c\(e\))-10.6(,)-307.7(p\(v\))-8.8(\))]TJ /F1 1 Tf 4.3931 0 TD [(of)-316.5(node)-317.8(set)]TJ /F5 1 Tf 4.8427 0 TD (V)Tj /F1 1 Tf .9276 0 TD [(and)-317.1(edge)-313.9(set)]TJ /F5 1 Tf 5.4003 0 TD (E)Tj /F1 1 Tf .6203 0 TD [(,)-313.4(where)-314.9(a)]TJ /F5 1 Tf 4.0858 0 TD (p\(v\))Tj /F6 1 Tf 1.9519 0 TD ()Tj /F5 1 Tf .8877 0 TD (0)Tj /F1 1 Tf .8137 0 TD [(assigns)-320.7(a)-315.5(prize)-313.7(to)-317.3(each)-315.7(node)]TJ /F5 1 Tf 11.8079 0 TD (v)Tj /F6 1 Tf .6146 0 TD ()Tj /F5 1 Tf .8764 0 TD (V)Tj /F1 1 Tf .9276 0 TD (and)Tj /F5 1 Tf 1.7641 0 TD (c\(e\))Tj /F6 1 Tf 1.9006 0 TD ()Tj /F5 1 Tf .8877 0 TD (0)Tj /F1 1 Tf -42.7019 -1.2007 TD [(that)-363.2(assigns)-360.6(a)-361.1(cost)-361.6(to)-357.1(each)-361.2(edge)-359.4(e)]TJ /F6 1 Tf 14.1069 0 TD ()Tj /F1 1 Tf .8763 0 TD [(F.)-358.9(The)-362.4(aim)-357.5(is)-358.3(to)-357.1(n)-6.4(d)-353.6(a)-361.1(forest)]TJ /F5 1 Tf 12.4737 0 TD (F\(V)Tj 7.4718 0 0 6.641 363.2314 155.6787 Tm (F)Tj 9.9626 0 0 9.9626 367.8235 157.3228 Tm (,E)Tj 7.4718 0 0 6.641 376.4409 155.6787 Tm (F)Tj 9.9626 0 0 9.9626 381.033 157.3228 Tm (\))Tj /F1 1 Tf .6886 0 TD [(that)-363.2(minimi)-8.5(zes)-359.9(the)-359.7(objective)]TJ -31.4972 -1.2007 TD [(funct)-10.3(ion:)]TJ /F5 1 Tf 14.5564 -2.1169 TD (f)Tj /F11 1 Tf 6.9738 0 0 6.9738 223.37 128.4094 Tm (0)Tj /F7 1 Tf 9.9626 0 0 9.9626 225.8078 124.2708 Tm (\()Tj /F5 1 Tf .3187 0 TD (F)Tj /F7 1 Tf .6601 0 TD (\))Tj /F6 1 Tf .4894 0 TD (=)Tj /F8 1 Tf .717 0 TD (b)Tj /F9 1 Tf .7682 .9503 TD (X)Tj /F5 1 Tf 6.9738 0 0 6.9738 254.7779 112.9323 Tm (v)Tj /F10 1 Tf .4471 0 TD (=)Tj /F11 1 Tf -.0813 0 TD (2)Tj /F5 1 Tf .6585 0 TD (V)Tj 4.9813 0 0 4.9813 266.1732 111.8551 Tm (F)Tj 9.9626 0 0 9.9626 271.6157 124.2708 Tm (p)Tj /F7 1 Tf .5008 0 TD (\()Tj /F5 1 Tf .3244 0 TD (v)Tj /F7 1 Tf .4496 0 TD (\))Tj /F6 1 Tf .4894 0 TD (+)Tj /F9 1 Tf .9617 .9503 TD (X)Tj /F5 1 Tf 6.9738 0 0 6.9738 298.0345 113.6693 Tm (e)Tj /F11 1 Tf .4471 0 TD (2)Tj /F5 1 Tf .6585 0 TD (E)Tj 4.9813 0 0 4.9813 310.0535 112.5921 Tm (F)Tj 9.9626 0 0 9.9626 315.4393 124.2708 Tm (c)Tj /F7 1 Tf .4496 0 TD (\()Tj /F5 1 Tf .3244 0 TD (e)Tj /F7 1 Tf .4496 0 TD (\))Tj /F6 1 Tf .4894 0 TD (+)Tj /F8 1 Tf .7227 0 TD (x)Tj /F11 1 Tf .9389 0 TD ()Tj /F8 1 Tf .4951 0 TD (j)Tj /F7 1 Tf 13.9589 0 TD (\()Tj /F1 1 Tf .3244 0 TD (3)Tj /F7 1 Tf .5008 0 TD (\))Tj /F1 1 Tf -42.8783 -3.0558 TD [(whe)-8(re)]TJ /F8 1 Tf 2.9022 0 TD (j)Tj /F1 1 Tf 1.0015 0 TD [(is)-449.3(the)-456.4(number)-455.7(of)-447.4(trees)-457.2(in)-448.2(the)-450.7(fore)-8.8(st)-449.3(and)]TJ /F8 1 Tf 17.4871 0 TD (x)Tj /F1 1 Tf 1.1723 0 TD [(is)-449.3(the)-450.7(new)-451.9(tuning)-454(para)-8.6(meter)-453.8(explain)-8.7(ed)-452.9(below.)-450.8(A)]TJ -22.563 -1.2007 TD [(prac)-8.6(tical)-396.9(way)-395(of)-396.2(minimi)-8.5(zing)]TJ /F5 1 Tf 12.1948 0 TD (f)Tj /F11 1 Tf 6.9738 0 0 6.9738 198.3684 85.4929 Tm (0)Tj /F1 1 Tf 9.9626 0 0 9.9626 204.6614 81.8646 Tm [(consi)-9.6(sts)-394.4(of)-390.5(cast)-10.6(ing)-392(the)-393.8(PCSF)-398.1(into)-395.5(a)-395.2(PCST)-398.7(on)-394.2(a)-389.5(slight)-8.4(ly)-391.2(modied)-399.6(graph)-7.6(.)]TJ -13.1053 -1.2007 TD [(Th)-7(e)-520.4(owc)-8(hart)-521.7(of)-521.3(thi)-7.8(s)-519.8(algorithm)-528.9(is)-523.3(illustr)-8.2(ated)-521.5(in)-522.1(Figur)-7.8(e)-520.4(S)0(1)-524.3(\(Supplem)-9.7(entary)-525(Data)-531.2(available)-528.8(online)-529.7(at)]TJ /F2 1 Tf 0 67.0005 TD [(12)-7.2(6)]TJ 34.5644 0 TD [(TUNCBA)-12.7(G)-334.4(E)0(T)-335.3(AL.)]TJ ET endstream endobj 7 0 obj <>stream NDLFIJ+AdvP7C2E 0mM AdvP7C2E 8jUd8<:#x' @2HP:)־j):PH@2' xq#:> endobj 9 0 obj <>stream NDLFIL+AdvP4C4E46 wr AdvP4C4E469{+;PWB> ( ||MO=B3^s587 4,# rd#!Gmv)qTf}zY{^: btxh endstream endobj 10 0 obj <> endobj 11 0 obj <>stream hTP0 A7E:鐪.:' !q{п')`[~{T򏝮1@c0n`p+0V*j8خ%dK-,NzR  6BnvU 퍝F|v{4) |Ξkf"&V:e@td![KI+ 0h endstream endobj 12 0 obj <> endobj 13 0 obj <>stream NDLFIM+AdvP4C4E51 l AdvP4C4E51#[j-e~~vVE=0c4:# jtqurf><$R?6sc:~} endstream endobj 14 0 obj <> endobj 15 0 obj <>stream hTP1n0 2HNVKu]hW@M <'E#w<\twd'?A=Xg4 [cK+ l*S[gȎ\w"9_"(h y|CVkoq kmdϞ[o~4ǦRS#fU>)\DC% `(iX endstream endobj 16 0 obj <> endobj 17 0 obj <> endobj 18 0 obj <>/Font<>/ProcSet[/PDF/Text/ImageC]/ExtGState<>>> endobj 19 0 obj <>stream /GS1 gs BT /F1 1 Tf 9.9626 0 0 9.9626 107.6031 715.4644 Tm 0 0 0 rg 0 Tc 0 Tw [(www)-8.4(.lieberto)-8.9(nline.co)-9.1(m/cmb\).)-291.7(Th)-7(e)-287.1(idea)-293.9(is)-290(to)-288.8(introdu)-7.1(ce)-289.6(an)-287.8(extra)-296.7(root)-292.3(node)]TJ /F5 1 Tf 29.9892 0 TD (v)Tj 7.4718 0 0 6.641 410.8534 713.8203 Tm (0)Tj /F1 1 Tf 9.9626 0 0 9.9626 417.4298 715.4644 Tm [(into)-293.1(the)-291.4(networ)-9.3(k)-285.3(connec)-9.9(ted)-291.4(to)]TJ -31.0989 -1.195 TD [(each)-458(node)]TJ /F5 1 Tf 4.7004 0 TD (v)Tj /F6 1 Tf .6146 0 TD ()Tj /F5 1 Tf .8763 0 TD (V)Tj /F1 1 Tf 1.0698 0 TD [(by)-451.1(an)-452.9(edge)-456.2(\()]TJ /F5 1 Tf 5.5369 0 TD [(v,)-452.5(v)]TJ 7.4718 0 0 6.641 251.0362 701.8581 Tm (0)Tj 9.9626 0 0 9.9626 254.7212 703.5588 Tm (\))Tj /F1 1 Tf .7853 0 TD [(with)-456.4(cost)]TJ /F8 1 Tf 4.3077 0 TD (x)Tj /F1 1 Tf 1.1666 0 TD [(\(Bai)-8.6(lly-Bec)-9.7(het)-450.7(et)-455.6(al.,)-456.4(2009\).)-455.7(The)-453.4(PCST)-455.6(algori)-8.2(thm)-452.4(is)]TJ -21.0266 -1.2007 TD [(employe)-9.5(d)-285.3(o)0(n)-291.7(the)-285.7(resu)-8(lting)-290.9(graph)]TJ /F5 1 Tf 13.4354 0 TD (H\(V)Tj /F12 1 Tf 1.9519 0 TD (W)Tj /F5 1 Tf 1.2405 0 TD ({v)Tj 7.4718 0 0 6.641 281.6503 689.8959 Tm (0)Tj 9.9626 0 0 9.9626 285.3921 691.5967 Tm [(,},)-288.6(E)]TJ /F12 1 Tf 2.0884 0 TD (W)Tj /F5 1 Tf 1.2348 0 TD (V)Tj /F6 1 Tf .7853 0 TD ()Tj /F5 1 Tf .717 0 TD ({v)Tj 7.4718 0 0 6.641 341.9149 689.8959 Tm (0)Tj 9.9626 0 0 9.9626 345.6566 691.5967 Tm (,}\))Tj /F1 1 Tf .9788 0 TD [(,)-284.9(and)-294.3(the)-285.7(solu)-7(tion)-287.4(will)-294.1(be)-287.8(calle)-9(d)]TJ /F5 1 Tf 13.0996 0 TD (T.)Tj /F1 1 Tf 1.0869 0 TD [(We)-296.1(dene)]TJ -39.0599 -1.2007 TD [(the)-291.4(forest)]TJ /F5 1 Tf 4.0915 0 TD (F)Tj /F1 1 Tf .8991 0 TD (as)Tj /F5 1 Tf 1.1267 0 TD (T)Tj /F1 1 Tf .8365 0 TD [(with)-291.3(all)-294.1(edges)-293.1(that)-289.2(point)-293.9(to)-288.8(the)-285.7(root)-292.3(removed)-8.7(.)-290.6(I)0(t)-285.1(i)0(s)-290(straightf)-10.7(orward)-293.1(to)-288.8(see)-291.6(that)-289.2(the)-291.4(tree)]TJ /F5 1 Tf 34.7408 0 TD (T)Tj /F1 1 Tf .8365 0 TD (is)Tj -42.5312 -1.2007 TD [(minimal)-261.5(for)]TJ /F5 1 Tf 5.0418 0 TD (f)Tj /F1 1 Tf .5349 0 TD [(if)-256.6(and)-260.2(only)-256.2(if)-256.6(the)-257.2(fore)-8.8(st)]TJ /F5 1 Tf 9.5146 0 TD (F)Tj /F1 1 Tf .8707 0 TD [(is)-255.9(minimal)-267.2(for)]TJ /F5 1 Tf 5.9637 0 TD (f)Tj /F11 1 Tf 6.9738 0 0 6.9738 328.8188 671.3007 Tm (0)Tj /F1 1 Tf 9.9626 0 0 9.9626 331.1999 667.6722 Tm [(.)-256.5(T)0(y)-7(pically,)-262.3(the)-257.2(algori)-8.2(thm)-259(is)-255.9(run)-254.7(for)-262.3(different)-260.9(valu)-7.6(es)]TJ -22.4435 -1.2007 TD (of)Tj /F8 1 Tf 1.1666 0 TD (b)Tj /F1 1 Tf .8877 0 TD (and)Tj /F8 1 Tf 1.7811 0 TD (x)Tj /F1 1 Tf .7227 0 TD (.)Tj -3.5566 -1.2007 TD .0238 Tc [(W)23.8(e)-289.4(used)-307(the)-314.5(p).3(reviously)-312.7(published)-312.7(m)-3.3(essage-passing)]TJ 22.1533 0 TD .0242 Tc [(approach)-306.6(as)-313.5(the)-314.1(underlying)-306.6(implementation)-312.3(for)]TJ -23.1548 -1.2007 TD .024 Tc [(th)-5.2(is)-296.6(forest)-292.5(search)-295.4(\(Bailly-Bechet)-292.5(et)-292.5(al.)-4.8(,)-289.4(2010a\),)-295.1(as)]TJ 21.4477 0 TD .0243 Tc [(many)-289.4(of)-297.1(our)-291.4(networks)-296.3(exceeded)-295.1(the)-291.2(capacity)-295.1(of)-291.4(the)]TJ -21.4477 -1.2007 TD [(linear)-302.9(pro)-5(g).7(ramming)-300.9(a)-1.1(pproaches.)-300.5(T).9(he)-302.7(message-passi)]TJ 22.0566 0 TD [(ng)-300.8(approach)-300.8(is)-302(computationally)-300.8(f)-1.2(ast)-297.9(a)-1(nd)-300.8(robust)-303.6(t)3.7(o)]TJ -22.0566 -1.195 TD .0238 Tc [(th)-5.4(e)-462.5(noise)-462.5(in)-466.4(the)-468.1(n).3(etwork)-460.7(as)-467.5(well.)-466(A)-3.7(lthough)-466.4(th)-5.4(is)-467.5(algorithm)-464.2(is)-467.5(not)-463.4(guarranteed)-466.4(to)-466.4(nd)-466.4(t)3.2(h)-5.4(e)-462.5(optimal)]TJ 0 -1.2007 TD .0241 Tc [(solution,)-340.5(in)-340.9(practice)-342.7(t)3.5(h)-5.1(e)-337(n)-5.1(e)4.5(tworks)-342(it)-337.9(d)-5.1(i)3.5(scovers)-342.1(are)-342.6(v)]TJ 22.2159 0 TD [(ery)-341(s)-.7(imilar)-342.9(to)-341(the)-342.7(e)-1.3(xact)-338(solution.)-340.6(Introducing)-341(t)3.4(he)]TJ -22.2159 -1.2007 TD .0252 Tc [(art)4.6(i)-1.1(ci)4.6(a)-.1(l)-445(e)-.1(dge)5.6(s)-449.1(al)4.6(lows)-443.4(the)-444(a)-.1(lgori)4.6(t)-1.1(hm)-445.7(to)-442.2(identi)]TJ 20.0933 0 TD .0239 Tc [(fy)-449.2(one)-445.3(or)-451.2(more)-451(trees)-444.7(that)-446.3(are)-445.3(only)-449.2(c)4.3(o)-5.3(nnected)-449.2(to)-449.2(th)-5.3(e)]TJ -20.0933 -1.2007 TD .0236 Tc [(articial)-401(node)-405.7(and)-398.3(not)-401(to)-404(each)-398.3(other.)]TJ 16.5083 0 TD .0242 Tc [(Although)-397.7(this)-398.9(modication)-397.7(s)-.5(eems)-398.9(a)]TJ 15.4897 0 TD .0238 Tc [(lgorithmically)-403.8(straightfor-)]TJ -31.998 -1.2007 TD [(ward,)-397.6(i)-2.4(ts)-399.2(biological)-395(implications)-399.2(are)-399.8(v).4(ery)-398(i)-2.4(mporta)]TJ 21.755 0 TD [(nt.)-397.6(T).6(he)-399.8(concept)-395(i)-2.4(s)-399.2(i)3.3(llustrated)-398(in)-398(Figure)-399.8(1).4(.)-397.6(I)4.1(n)-398(t)-2.4(hat)]TJ -21.755 -1.2007 TD .0245 Tc [(example,)-465.3(two)-465.7(d)1(istinct)-468.4(p)1(athways)-472.5(a)4.9(re)-473.1(connected)-471.3(onl)]TJ 22.2956 0 TD .0237 Tc [(y)-472.1(t)-2.6(hroug)-5.5(h)-466.5(s)-1(purio)-5.5(us)-467.6(edges.)-471.8(The)-468.2(m)-3.4(ain)-472.1(d).2(ifference)]TJ -22.2956 -1.2007 TD .0244 Tc [(between)-340.6(the)-342.3(t)-1.9(r)4.6(e)-.9(e)-342.4(f)-1.1(or)4.6(malism)-338.4(and)-340.6(t)-1.9(he)-336.7(forest)-337.6(formal)]TJ 21.203 0 TD .0241 Tc [(ism)-338.7(i)-2.2(s)-342.1(t)3.5(hat)-337.9(t)-2.2(he)-342.6(former)-337.2(one)-342.7(connects)-336.4(a)-1.2(s)-342.1(m)2.7(any)-340.9(o).6(f)-342.8(t)3.5(he)]TJ -21.203 -1.2007 TD .0244 Tc [(experimental)-297.8(data)-296.8(as)-296.2(it)-292.1(can)-295(in)-295(a)-296.8(s)-.3(ingle)-296.8(n).9(etwork.)-294.7(A)-3.1(s)-290.5(a)]TJ 22.7053 0 TD .0238 Tc [(result,)-295.3(i)-2.5(t)-292.7(w)-3.7(ill)-298.4(e)-1.5(ither)-291.9(h)-5.4(ave)-297.4(t)-2.5(o)-295.6(e)-1.5(xclude)-297.4(some)-297.4(of)-297.6(the)]TJ -22.7053 -1.195 TD .0217 Tc [(data)-293.8(th)-7.5(at)-294.8(rel)-4.6(a)-3.6(te)-293.8(to)-292(dist)-4.6(in)-7.5(ct)-294.8(biol)]TJ 12.8322 0 TD .0238 Tc [(ogical)-287(p)-5.4(rocesses)-285.4(o).3(r)-291.9(a)-1.5(dd)-284.3(spurious)-285.4(edges)-291.1(t)3.2(o)-289.9(f)-1.7(orce)-291.7(these)-291.7(d).3(ata)-291.7(t)3.2(o)-289.9(c)-1.5(onnect)-287(to)]TJ -12.8322 -1.2007 TD [(th)-5.3(e)-263.2(t)-2.4(ree,)-266.7(while)-268.9(t)3.3(he)-268.9(latter)-263.4(one)-268.9(allows)-268.3(the)-268.9(c)-1.4(orrespondi)]TJ 21.7436 0 TD .024 Tc [(ng)-267(nodes)-268.2(t)3.4(o)-267(b).5(e)-268.8(i)-2.3(ncluded)-267(i)-2.3(n)-267(d).5(istinct)-269.7(t)3.4(rees.)-266.6(H)2.2(owever,)]TJ -21.7436 -1.2007 TD [(th)-5.3(e)-314.4(f)-1.6(orest)-315.4(f)-1.6(ormalism)-321.8(is)-319.5(able)-320.1(to)-318.3(locate)-320.1(d).4(istinct)-315.4(b).4(iol)]TJ 21.2827 0 TD [(ogical)-321(processes)-319.4(i)3.4(n)-5.2(t)3.4(o)-318.2(d).5(ifferent)-315.3(subtrees)-319.4(through)-318.2(the)]TJ -21.2827 -1.2007 TD .0236 Tc [(articial)-298.6(node.)-295.5(T).3(he)-297.6(artical)-292.9(no)-5.6(de)-291.9(and)-295.8(e)-1.7(dg)-5.6(es)-297(give)-297.6(th)-5.6(e)-291.9()]TJ 23.1093 0 TD .0239 Tc [(exibility)-295.5(o)-5.3(f)-291.8(g).4(enerating)-295.5(s)-.8(everal)-298.3(subtrees)-296.7(without)]TJ -23.1093 -1.2007 TD .0242 Tc [(paying)-329.4(any)-335.1(p).7(enalty.)]TJ /F5 1 Tf 10.959 0 0 10.959 107.6031 440.5038 Tm 0 Tc [(2.4.)-496.9(Tuning)-327.8(the)-334.3(parameters)]TJ /F1 1 Tf 9.9626 0 0 9.9626 117.5811 422.5889 Tm [(The)-299.8(parame)-9.7(ters)-295.3(to)-300.2(be)-299.2(tuned)-298.6(in)-300.2(this)-300(problem)-299.9(are)]TJ /F8 1 Tf 19.4218 0 TD (x)Tj /F1 1 Tf 1.0129 0 TD (and)Tj /F8 1 Tf 1.747 0 TD (b)Tj /F1 1 Tf .552 0 TD [(.)-296.3(T)0(h)-7(e)-298.5(number)-302.1(of)-293.7(com)-7.6(ponents)-301.3(of)-299.4(the)-297.1(solu)-7(tion)-298.8(\()]TJ /F8 1 Tf 18.5796 0 TD (j)Tj /F1 1 Tf .552 0 TD (\))Tj -42.8669 -1.2007 TD [(depend)-8.2(s)-246.7(strongl)-8.3(y)-245.5(o)0(n)-251.9(the)-251.5(parame)-9.7(ter)]TJ /F8 1 Tf 14.0727 0 TD (x)Tj /F1 1 Tf .7227 0 TD [(,)-245.1(but)-249.7(it)-251.7(also)-247.8(depend)-8.1(s)-252.3(o)0(n)-246.2(the)]TJ /F8 1 Tf 10.9657 0 TD (b)Tj /F1 1 Tf .8024 0 TD [(value:)-252.7(e.g.,)-249.1(for)]TJ /F8 1 Tf 6.0718 0 TD (b)Tj /F6 1 Tf .8877 0 TD (=)Tj /F1 1 Tf .8877 0 TD [(0)-251.1(the)-245.8(op)-7.2(timal)-250.7(solution)]TJ -34.4108 -1.2007 TD [(is)-426.6(the)-427.9(emp)-7.6(ty)-425.4(forest)-429.7(for)-427.3(all)-430.7(values)-433.2(of)-424.6(othe)-7.6(r)-423.8(para)-8.6(meters.)-433.4(For)-424.6(othe)-7.6(r)-423.8(valu)-7.6(es)-425.6(of)]TJ /F8 1 Tf 31.8216 0 TD (b)Tj /F1 1 Tf .5577 0 TD [(,)-421.5(while)-436.2(some)-430.6(subtrees)-432.2(are)]TJ -32.3792 -1.2007 TD [(composed)-276.2(of)-265.3(a)-270(single)-269.2(node,)-272.7(some)-271.3(others)-268.4(are)-269.6(com)-7.6(posed)-268.6(of)-271(a)-264.3(large)-273.9(numb)-6.6(er)-267.1(of)-265.3(nodes)-274.3(in)-266.1(the)-268.6(resulting)-276.2(forest.)-270.7(A)]TJ T* [(forest)-344.3(with)-348.2(many)-344.1(very)-342.6(sma)-8.8(ll)-342.8(trees)-343.4(\(a)-341(sing)-7(le)-341.8(node)-346.3(each\))-346.9(would)-346.2(be)-344.7(obtained)-345.2(with)-348.3(very)-342.6(small)-345.9(artic)-9.2(ial)-345.3(edge)]TJ 0 -1.195 TD [(cost.)-322.1(Th)-7(e)-321.2(limiting)-325(case)-328.3(in)-317.3(the)-325.5(other)-323.3(direct)-10(ion)-323.7(is)-318.5(a)-321.2(sing)-7(le)-319.1(tree)-324.3(resu)-8(lting)-319.4(from)-329.2(very)-319.8(large)-325.1(art)-8.8(icial)-322.9(edge)-325.3(cost.)]TJ ET q 430.485 0 0 204.435 107.66 129.713 cm /Im1 Do Q BT /F2 1 Tf 8.9663 0 0 8.9663 107.6031 113.726 Tm [(FIG.)-417(1.)]TJ /F1 1 Tf 4.1984 0 TD [(Conceptual)-419.8(illustration)-422.8(of)-418.9(the)-422.3(Prize-collecting)-420.2(Steiner)-421.6(Forest)-423.2(\(PCSF\))-420.1(algorithm.)-417.5(The)-418.1(left)-422.1(panel)-423.7(shows)-414.2(an)]TJ -4.1984 -1.2203 TD [(interactome)-420.8(and)-424.6(the)-416(right)-425.5(panel)-417.4(shows)-420.6(the)-422.3(Steiner)-421.6(forest)-420.9(constructed)-424.7(from)-417.8(that)-425.8(interactome.)-423.8(The)-418.1(direction)-419.8(of)-425.3(tran-)]TJ T* [(scription)-266.8(factor)-264(to)-262.3(target)-265.5(and)-260.2(kinase/phosphatase)-271.8(to)-262.3(substrate)-266.4(interactions)-267.9(are)-265.2(pointing)-261.1(toward)-262.3(the)-264.2(root)-263.9(node)-266(\(opposite)-262.8(to)]TJ 0 -1.2266 TD [(the)-270.5(biological)-269(direction\).)-273.1(In)-267.2(this)-266.5(scenario,)-273.3(there)-268.3(are)-271.5(spurious)-270.7(edges)-269.1(between)-270.4(these)-273.2(two)-265.1(pathways)-275(in)-268.6(the)-264.2(interactome.)-272(The)]TJ 0 -1.2203 TD [(PCSF)-333.6(algorithm)-332.4(provides)-335.1(the)-333.8(advantage)-338.1(to)-331.8(connect)-336.7(these)-336.4(distinct)-338.2(pathways)-331.9(articially.)]TJ /F2 1 Tf 9.9626 0 0 9.9626 107.6031 737.4045 Tm [(SIMUL)-9.7(TANE)-9(OUS)-339(RECONST)-12.2(RUCTI)-10.1(ON)-333.3(OF)-340.6(MULTI)-9.5(PLE)-335.9(SIGNA)-9.9(LING)-10248(127)]TJ ET endstream endobj 20 0 obj <>stream Adobed         s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjzm!1AQa"q2#BRbr3$4CS%cs5DT &6E'dtU7()󄔤euFVfvGWgw8HXhx9IYiy*:JZjz ?N*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*Ӛ)# ʖ^u< oǂx(=*<S!U8wHvGwc9]Q]NWaTqW<S!U8wHvGwc9]Q]NWaTqW<S!U8wHvGwc9]Q]NWaTqW<S!U8wHvGwc9]Q]NWaTqW<S!U8wHvGwc9]Q]NWaTqTX ΍pePSh8;]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]Պ^dثWb]v*Ĵm&rߧ #/QPNߠ=U~f辮Q֐޼\[cE]%HЮV?o\x㷳ԿEDӬH%O#h6*AmKI ^892*@4VX4CPv/yXzq$ӕU!8ھ i,Gu;,G|}yvE,V2l= 4ۛ_Ġ)owS(%+|<2zRQtio1J*UثWbO /wOeWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثUv#V7c@bnsGT*wng0W}n9w*ѼW*_XHeHKEՑVN\GAOm2 2]eNjnLԜU^[KukeA4rLIn0qT?: {&uuwơ$B+WQ(OS׭<1TGnl[z.f4"K%وh**Y*UثWbO /wOeWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثUv#V7c@brkA_|V* ֛mGL;)luhfChqmⵁ~PƃUWb]v*UثWb]v*0t8qVYv*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]['m?c?/|00*ɱWb]v*ԍ^ |Voh5+Yn[kkf %ۘ㳑x# qTci_bzPUt!hȯ.SRiN:ϾZ4o,Ip^SyU1^s%ۘeqHqTLxm= y.K%8UZ^,ÊWC?Y~4ߤw$Kny-T7 qV14kc%ō<L  :b3κ~S93nR=G#(WhY^*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UlݷU~XO'FoBrib~[y?jX_+Q~ן5-ǀW(֏^o:L5SCyO072QU[OtF9EӒn ;Mc>ڸbv# E{-TZZWLK DȌRV U/?,Ao{1oI 6LqxrG^=늷yoa}A\݋ S"5Xޝbk}2Qbu"5UzyjMmwF{ȯf7wQH#F(pZCSPyRI&(x%yd~y]%ܫI"VX"4'j/NmE(,糚ՒBXH$9$^ ߯Q/uKvx$U z}F&|U5 ^uk\}ac(%PK,c?gI=T|騈|RZ$ieXiRqzxuwlU/ƭM6ʹo$)-[ih,cA/6yLu$:~EcJh>|apMEhqTv*UثYf*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UlݷUX&X|`AgYӒil2Ml N nl~$4'=[ձۯ<-⽿ޱDj|z!S9 k5)zb$X5*b8+UC3" RHVV*AT.t.#%)U`UllUm֋]n.vr#u+LUSvIhMn Q1^Jثv^],UMTBIJh+UҴQF\4jAHe>*nz[ʕ E;J|UF?*f+)lcmpku0 $xb[K[KxbH-c5 <*v*U~aunp⬯v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*OV*,^{`a UbX<3Ok>iXx#b|1VA 1CC ,qFc@ 6]v*UثWb]v*UثWbO /wOeWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثUv#V7c@bv*5[22I Y71o8yA}e幬3tZW] 8"H\PWb_]\jmZ%/'*1$䟄㊦,1rT7eUn$ sk*y[Asn@ O_ Utl2.mU@bM|T8V)./`8yc"^p㊂X^$VT.?0wP^qy5كeV TyA$[_/?OiLUJ/7vӡ7)n#\CAMLU ck:cCZ-бteWXzU} WӁ :tQat l}K$DCi7Zַ,<dCQSUثV&H0.5% ȱL튤W?:\B%uA,!(z|cP;⩞=Jk mn^+,$0DU~~IJFتˇVT/qu]kWqTaq'--6rƲēK$I>S5ߦ*^^4Nncx`ڴ}U+!kw׶oX.`mwdVNIf,%t^#.IFS|U~aunp⬯v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*OV*,^{`a UbMOKvYGx$WҢ}bI[ J܏HSlUثWb]v*UثWb]v*0t8qVYv*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]['m?c?/|00*ɱT&EYãJ8`O$x-{8,|pYHۋkxRDOfyjqUK F+j é V9)q%:*j7mv*$q%Zb*f!TnIuEi]p Q㊭ybFEwUiԐ +AWb]v*Uaunp⬳v*Ӻ"3E7$z| Α}՛* 0銦+N*UK+J׾*E+p PzUv*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]Պ^dتK"\R^Xe⍏wSU%ֈY-'aH]b**UFQWgDh3_P8*OIK/4cmXG$oX yGt'2{mM_D#3gM7QZѥQpoďlU~[j ڍFbc ecpX-iDLUb]v*0t8qVYI#D7$[Ξt#A[67~ߩ%v&g'm*pk^V&E 5$ù= rE\^;i~kթY⧱]{<}櫏:'OJKE'r]T, fSLUoouJUnc)6)$ 13&ZƝ1TZfs9<=ۙmf3ə_S[Z:Xj4QZGh `E{m-Y䴘$|(˾*/1ߦElMKhc9ʷ"*NjıRIFCޭǕkSjtY*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]Պ^dتżI*6VSbJzuc$sė dn-AW,UX$(QثWb]v*UثWb]v*U~aunp⬯yN =^Zw/)+zFH!|^1 4vK;K;X$>7hXA_LgW@}C;k԰V4!|N߫|(k!ls}w=זU5i܊64ʜ_+A{'qyT!xP`㱧C*Cis\Ejq}rXh]D6 ו>U.>ROklח28OIen⩭\Oʹ+VRAUqWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*Uت?oX{ 1VMZTVvf;*I&B&R4Ư>e쭡@10+ ͎2M*.>f}e$nMoZ)ۜg½Glˈw~=L8Әf[UdE/4αF4UU$43ywWHNH)Rd* e̪TT-Y`C*¡A+ Vm퐨y\AvOhzdZ4Vo*,8Y jx}2䩯J^4a=kј.[9ә8x_ (/k+%w^ΌU~E2'~FF7GZ󝍿LuTY$M3:P"b$jއO0G$>Jv%k8-8}9>KJЅlUƱ{6mIuE4R3jD@!ZpL~jizpKsȟ_{ Ÿf1zeI޸.IHy,n 1jŸ}Ry(m.U.5#AkXݯzv5%w.8(>ytv"XZ~*6aK/婞I'"T[2U"76b>N{]?I :-’\K jHp!4%hUaunp⬳v*4=3\&u(Dֳ =Te=v8? 3kN4wgcw+S 7!Юة/򗔵4Pbg` }8!?*(Z{h;ۺVi .g^]2SQ7.@ 27+,:^ت;Z{]7OGZJit,ت.[CG{oWMz}b#.Q*%#j ǎ*hIu Uv*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]Պ^dتQӬ+obZ)IcnPE^[{8dEWٍDrFxr *:;qG3'y#FbI桸ޝ(̍k ;v*UثWb]v*UثWbX^^'*1Wb^ ?|k7:}]l"flψfA<VX5%i+I#M~x8< j$V вGi}J#KRr7\(I4+O׹Ǧ$jvv+M[SYnan7|U~qgsymŢVf݁튧Sjzl 512U!b 9 UXZ8d;J ~#1U; {F$)NT`LR((*"G$F* :U!v.Kh.gŸ\4pum:Ot=XY5DmBʕ2r8T7UsKD5n׾*PjCv*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]['m?c?/|00*ɱT>\'R!'n!Cwu8gK~?"bԁ1'W0٨J1~;v*k>fLإs: a-#`تIyVҴWˢDQFӴIaI38;HP#WU@5;)~bm4nժ׍;^D~,ܹq(LU^KX(f  UwҾH*7c˶)VRTۯ8_FyW+RMB?gHDʼnuvk&͌6@)P{qSPmi+rT5E>!ޘ_ږ$.KlhÔrDO~8yvSB:$Z}lU$󺤳)+JCCzD:dw/dUeN**eRA;TRii.$*#qhoIsA$,۹AG'P`A ȎwU/HHe~J*ePJbRʤ WGGqSTlqULUثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb"튰+>mtm6͌Vqm-݄k wQ=r늻;]oqW|Sw˭*nu]M.þ{ww7ܺ[\U=r늻;]oqW|Sw˭*nu]M.þ{ww7ܺ[\U=r늻;]oqW|Sw˭*nuTe_n5o2孅WlPRH;fWbR:h.5P փ8Ga:jє--GX:ϔ2֮ܩP_WŬ Ln۾إmԖmKOHY#vv@ ZbWrѷ_ U7Q8Pn㨯qR(ldUYq)eS^8P錒ѐ*.Qs7#⨙$RD*:{iŦ-fbYKZ:b_\A}gS86 t=T[Nދ,b4{t{7%w~8SҵWLV{rJn,;b5 t HA*ZRZm%T+_jQ+]*v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*Uت}9u+;x;5@Pq$&?(JUzAQR rA)@d^w*ԚX)pثoiahLaxU㊠5E/DG8- о,Q1Mim+ͽP تɡh)T$ҭD߼w'D[ m<0,7W M +OLUN&ۛk%RWkrhVWTҙCwSA_]8dVAL  ש#a9Yc5GScZ6a9}e%7Q/Z_z P\RT`;j<:O'F*֫.n~gEP=Uo+/;@+Cov*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]@tu5 CF=1U jV%SYVTנ*KO·uTT^)HTpf"e}*6/{Kn4AክuuR `.*=qT:eϫ^ RըщyQZ(X]|Oc^ت;v*z1KHH'bVZusۀ[Ums.UO~ UV$pz5Ulo~1tGA_h_\kq*׵+HoH,ӎ0 Hvb;64&xh+zj(S /X}omȁ4b(hUPW;⩬<+4Gn**k;iX՞2Qӯ.o\VJw$xս+嵎?[Ԟ0r^5ޞ4[VdTQR>x-pۢ=*;^;Hۼ^_d⫥ "MĂkbMSIxnKbЊ8Zwbh7QW:A<%UA1TV*U noB+H+ORg qTpֺp$E3/NqWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]3My}Yyrg:Gi R6/.¸oNl[}cqV?M*=d>kղ(tzd~UE,rĒyG"F ]v*UثWb]v*Uثׯ;V//i}Vg: rUcՕ ^S+6ev>>n@k\wVE%Ms} YyMHE.}r銫=5 Qɯi#naQֿت}*Z<%Y<$P-rMT\˭i<֝fbRyK{wolFu4-b-wDP *WqU_Қg#⭛< DCڦn%kIbC'Wu])&aJWԬ/ ޸Wuܩ4FAWTb]CM.Q j~*Wӧi- 0n5'~W#.TQ-H9%Q)OniZœVzR+^Z_zf};ӒCY$O=6FB{Ub]v*UثWb]v*UثWb]v*UثWb]v*UثWb]Ve|7cǷ(*qTm˫du$kڒkQ@דxT/B$ _W]v*UثWb]v*UثY`޵K{miqm_ڎ 8⬓bVh4Z;CpZBM2 eSPwt# b]v*UثWb]v*UثWb]v*U Y\XM饨j@j>Xo8YAVuR˭] (SV[iەYþ*~ $_bAqV/)ւ6z*HSSӐJ f@mFFqTL2ܣI OiBou*_, ߺ}*{Pt*ych{S'gp[ɪp}BH!ݗzTEߥڽ&+$mت'v*tt0^W!ծIsDy%nX\rQlU$VκVvrEhՔ4pTƥR*6n O(}3"mX%L{izEr_!GwF Bmh:3VIgUKT4Q[(| 1TW?_dXUg#ɟ`Ӷ>ъ`Lui(>!w >تNeB!QPy7wxtxTt?.<#ro.鵴C(V?)xT_kQJ"*KFvJjr[>_ԡ:w7LU$.Malv qDO\Ֆ1ߔWfJEVE0"Npu`yX'0Rߏ^Y1APA'b]v*UثWb]v*UثWb]v*UثWb]v*UثWb^]Gm!}o^![֪j;RSg˸lCko6yGzmuf@Ԕpo96G>x>N[.eԵ;d;&P `z %b3cGɒjv*UثWb]v*UثWbR{@TX&wԬؽ`Q̧*[uӍ\K v#c] o8z[tSҟЋMm(glŞmJe"Bw'zQ>9}Cz_=y,vuwo/߿Q|-??GPwg4ڽ'S+`1}7[iN:8eۑp:;2XUثWb]v*UثWb]v*UثWbw=܊QDPH[նzhv늩jזf`ՊYwUbzޢJG7nWei8J9X^ثi=!xnP4R=c,BP;h1UڕSڣqZvU8#F| +3jerWr.?؂1T\(N$#֌m銣`wwCnY#7F `TO)Acyo2jQzT Vr̷,٘ˋ:M??9{MҼX}ڝܶq;Xr ۦK$q4hdØA=ގ4}9 -@ "E\[x6nEUu51UyBT8 4"BTXXH1b'ӊ7̖r&MBPPHS7&*U,"uP&QWe{m9F*|X:~j2 4IJuQ֭c~"GPv$u8ZL޵O Y*G*-o,IOaDbsWދexeˬKKӔM*jPy]qT hs ӷC+S{q N+&-m|M"'giw>N*ԼX8=@%$6튱9hluݏ./e f!fHd0PF͕'g7YA'U|=J};^ ,E `F؊wg3EQ1O͌I;2o&2Ls~,ohσ~!dzyVA^}y7 ثWb]v*UثWb]v*UثWb mm%Dr QԩLU_PPƌѣVZm,'.de+o4|<$T} HU>_U o֟,Uѥͷ G8jS0Q'bn㰽Y'z^݊NWKuQ1b7b{o)H3_LbX^8euYT%zӭ1U8l-kt$uNثV772j1TTMBM>; _4R/V qo3ZO#`T4x^;/07HAh}X強:R}1DeYRx)ت2Cۨ.th4$NW5}6E>ѼB'㶇NS@8rIJ'ƻ*UتͬW4P׉\UU7^LԱ+CjވAf<=21y;wN9DAzJުZcō İ@y~XT*vڕ##Y<\ ss}N}'p~ T~byԡo6v/ ۧiwr9}~e^Y|ߥ4MH?וM)I"?.Ĺ:^.\9#_qf6M}2n"{YG>vUWb]v*UثWb]v*UثWb]v*UثWbvh-y%V9Hu?qTu>̾zEgqo=ۙc8SFKym!&%d3sRߐv}n<i}=si]u`AR <Ay:{ZnyjW,K(4|^q/'z^݊v*UثWb]v*UثWbPZ֓gi7z]󶼉{0G22mX'q6)ukySUjZK~J+خVmykXc3/z{Wb;wRI4M}>([oE;vLQd~?b3'}4Ob宕u#$g34oTHKC$4Zֹ^<|>?]:\03y⸅fF7?^4OR+ |:y D55żRt rț!ÒQ%jq=APrBlm_n\Uk֘&S,)!F؏*䡚0dnUM/c9ڸN{G4OHËBZQ{z)k5$D60^8(;{b5mkp&{H)LUXXZicoCPBj<T1U^ۘd%V|}cY8$/zK}a[KncbqU9<]ڐz jL6\URP˷fL!#aibkj]>WzY55aybiWUf' TcBС.5 &YSyc2Nhر;F99wpY?̞^` %K';2ujZya,rAjIc(*(;v7FKP6ݩ኱O0ZhZi2ɡksS1;=߾S< 6.I1ǂc~,~ki_OX`#!2#$|ܓ5#M*%z6GmԴ须b!/p29p5e*^9ZZnC%Xw)8 ㊪wm$J*2#U]v*UثWb]v*UثWb]v*UثV5cT:MJc eǻ|+_\Uy5O#ҮJK*,uWG5,U^{e<}ZE&9 ô^ M 8 ! BIDGPUثWb]v*UثWb]@ >=in3 kGtIEcM :$:銫xnfVaʠWc*hVPcekǃS>*WXǤ:0} ʎm9il>&^$;{#9cY#` AA{ E`5P`P7-$S҇t=%%4(U^9cYр G*v*UثWb]v*UثWb]v*Uث֖EV=ͅ+oA-",DQÓ+LU1g.mE:@Eyh?>U&yP?K@#( P3j Ub^{uyߢ:mҏG( z?l>{ /tn]v*UثWb]v*UثWbPg跚M򷽉nCfwF7H[OԿQWq( FU[Qm`3C{ugb]-3N-QCyb<#3J$v6n2Vr; 2٣qu,Q"D8~(-t8x=w8@-uMs^'<ĐϦkX\B;sV"i|UثWb]fTzp9}ت*UثWbPlSjVw/- RG~\Z z*В wUQoO+7qQd(wPq~j2 U { 4m!hI$STk3H[淎GCqVK r3jힿ;@[C$)ЪI;1Tɼq*u9}Y.YH@>UXzaMCJbH)U̚di^+vrj*}6M]Avka8`pe+NQ ƻ%+-~TҜi uA.NSҬ%ӯ- OoEݔ>S]o~`H"~RߕA-+WѤ?| ^w ebn$Q_qZYy -ݽ!T.{,彼&l,QdK#H|1Ѽ]s֮y?&O *B^g{o:R.ldԆ1V^VqZdj,)ڶ޸Z?D`R]XXkRHF*Ҽ冶ol/ݴW3 I8 {{te!U kk{ "*WjTg1"װ8#v*U >m5w, u$TC_A%j$?έFCM*3]Ql9_ 1CӦ}.]YW__JRD (s米d8Q} $|GJ$e9%Dan1@ur"X#(hԎLj_pt][>uI3A{n[44ӍŀO]H8!d&Q6o"ij..ٺwz#|t WR[ Y+&jh.^ ulLj캷Ҵ#cGpī3ծh/㸐p%jRe$*[4@IM\|$VDx0j{:PQtAӄy0ɖ0"Sz'_44rwI1 k G}Wb]v*UثWb]x7i?*Ck21BTWnWtuW@ #0 (>" LUT*lv*yn8 6ܚ ޠ?<[dl~{=EA=Wb]v*UثWb]v*UثU O3KUEI?!p7n|yhM&VRI^N1ڔ3'zn$a|tc ]&:+1*R7_9tuh2 ~-<;1hjuT&ݣvtjx"Mp2v*Uث׭<嵞$aOz$fLUBjךU o<2$qe :п8MWMսh$[G)JuRsyqrdeqˋt/˦4kSOm:S#AH&?iSاL.KƇ{DWx[yw"͌[m#KC&1eMҟQHw{Zө@>l|"Ƞ9m YY- Qk9unCEO`j# {:.tKuh9T%dDg!/|9]Z <'.Hc6gv$1ܒORsu<2hFx}Z$]q5(Gk9Nɑ\a rDUتI}RYUuI;y\rXcE4쿵zF*m,}{+P@ RћgmGFZ J;5(F* +#XT_v*UثWb]v*UثWbXHZT՚J7|Wb~B,C W7kק!ᚽG^ѿ?Kv*UتOmP{ WO\J\߄JAE.kpϣޮA%)$:\&=,KsX׶>0\Nx7ǷcxǜtyK@5B%\BG3ŗ%̷e?7~{҄ \Jôq2}99e.5}'ZUثWb=cO:=M+ZAኢ`Fя&E @qU[k\6.[A*W]jUnkZlU@#~xKAI^ j0Y>$*0S҃B/§njIͿ U&՗P]_y QHB=ry8_8Hdw0IzDP]v*Uث#G䴍 J݅Ηv6hc=róuOxQ|cȽOC\\jfIbzT`>!6]2zw=|c*]kWbX/5ۡPo{w(~}(Lhi<3n?!:_i/*O27.M_*=/^C|jlZz}f@0@(<3R26]  "UثWbw1zZz_BGMiBK1TRTAwZ]ꬢSV/ܭ\)|'*R7y~Љ!e뼽O1MOPo5Ư#v%Gmqbo I5F 緞;yXk,DOolUbտ,-vޛKSE&F糺w t::gJ*mrV_e߆*ZjZuFE}N*卵kXlUN[׆;vRa|1T^*U ));aIa;zb$ J! q튢ԣ…NU ->k*F cbx⪶-4f;؊ִUTޛ.B&ã+ ՇcQyuXA@'eR2d TçZy ֿ}OW_.Pzw`EZ6 NeSdwvm&< LW$_=μ^ۙ0MVP_^FRkwfxea$Krwf"3E6_"H.~YK@[[f?oUAf\pVEثWb]v*UثV1Rш4>䛨xM$CWͮڑ#S;R]{#!o7\K}L{|r/a=W<=,=0ލتK7W 7O-g쑧Rrj'=iV/o#zTgtp@*e#vv:| @NGDv}_B-Z)K{v K"9!Vߝ$L 4 ʿij6+e2ñx'.B=g̚g[}_M#̧N}^x2s?dgb]v*UثWb]v*UثWb^1 <_<ӈ5:i,$ܶ*ʌWn ۛP2Zz/c#Q)oGQ}uٕޛlpc$;CC-4N;!e Wb]ymm>~6gA$=|\C1tϟX^msռW6%eE"V|^ ĐyL,]v*UثWb]v*VPĢ^sކj#eS}qTA7ƭGn% ICCG寗'Դt.4𸫿P~~Y/+b)gYK)a rъ]5%&"{qUZuH+f_'??\Uk~cffM/w^FqJ[0|2ȓyNdΑHGHOኲ[[;qtx]OҤ⮼AЌUBy,- 1#W(jQZxLUeaFS 8ɯ3/fFhhYX7$J2g|Q%}L57[M6a=_uaف،2Xu:kx3?日[]Eum"o:! UA2 IB.]v*UثWb]v*UثWb]Yt}[s8jQ-51vKqGC$Yt/H+d:b]v*UثWb]6ww/;[,IRca4>JBTҦ/CI~)8>\ X@z=U\U~cujuiHX~4m2p(..E7=]~Hn.oShdPGNHkM2S)s-zncy@6t*s~F`7] 8,)4DV'He 嘄Ȱ(*wD XAu~Ԅ}_\O(<]*5S0w[hMmk6Vǥ) .YdȪ[_CXj6Y]KOVtY#n$04 UO~Wy0,D֦ >'>v^WhbL๭Z:޼VnX~vռȗ]h =} m'мU[o̟'K2]^*TK+>'OR8R,m$ÒWO4d>#UT5旦_!KH.YIUY#y-SD>p ?b}(_C\ߙ$RūiwmqjH&9][̿w ow[zp X Qk*k vkNHM]i-Ť/㊼y~Hj]խ/MSJ7vw.\?cqK{C3ZIpi{-WV(xBYXTFdo=8 ![ b_Tn%5}K1!?az!Rf-XppzdWb]v*UثWb]v*UثWb^c]+P/< Mݰ>d#BktƜLt0e5?DޗiZA,w($UA#̈a,s0Vb]xg,4w%eYhe;$2:a mdl/oD޸OZޣ*6;GWSw^Kޏ/3] X]U㺷\χ;/1%Cv*UثWb]v*unVJ 3 T2x֟ d:f*A%0%sĨUe%ZpTPPaiڄ+qgr&GcQQlÖX'R<~}}|JiӒX$vuQxOkqGW8LyK-j%hڴ ̇u[$D# FV]v*UJRu?5`F*ƥM6pƦ]&y,}-*ߟacu(A!-H)& V:yFH.Ӊ$Kg,⩖ŴzVor1VD jU}cA2QoUNlI7LT9SFb8Z-n aP|1V Yb&q^ت_/-yu2Ď~ #؇]y/˞F@YKK-UXYbdoL$4~>8{ї6iZ%aifKǜYwQogKlߎ*KJށn4]A@1WmqX~U( < "+Y)쥖TbF*Ƶ:]sM^8Ev71^nQ\(cRʶz+6HoTj$(8 HrEثWb]v*UثWb]v*uumio%̫ *^Yd!UTu$(@Ȁ;s_2iZM/(;x܁Gj Sݿs#a^|Z':GL˞Z|G6oln۫1Ajy3Ϗ!dwb]v*y˺gk'RԶZWt=N#8 .FU<w ?^bQ9jvGڏv fSd{GK ?T/^ثWb]v*UثWb]v*UثVё20!PF)Yqvp+K-VZ@c\95>??/G;G c'XePȆ ;rQ14yثWb1mƲK2$fH}43 t1e:&Qek=Ǟ$+M!DnD]Y9e./3^]v*UثWbRFI$r-vr#m⩆*U/56zA㺘C$|UZ;ym$-NP*]1~b^M&fvӊ3[" ykav#<G^({>+jvvP:Wxs]wi80rfsRd)$hO8AVyn&TSHqU|U e]DFchUu:⨬UتG?)ii. ?_$Czd2@HSON?;/7jSO?<4iBaw{)giχ=ŗE|)-$ ѵ^6.cS:tH`IG**UثWb]8^2(uB*6RWLMBdPdd4~'RW_; @wmˤ@*~d.cD?z i=<={nqU]Vmw:6A5p}p>qbw$jnO!튩`'DB|u%Ebp5 GgiO-kt+,7f^)BF5xcuLy限]bֵkE/u Kb\ykO|%DF/O~<ˊXc!R{7$ e ŊY$#dntO'ݩKy\O)9& ^8NEثWb]v*UثWb]'45]Y4TUK~f|Ij ol(ݑ1b"˓d> bqXҼ$A+5>̗DP_s] O?Y^kkmioK*(UTt ~s2$dbUثWb]c>}TgbkMZ̻ZWv:y8-^>}Rȍ`ŒauB$! P qz2^[\s rF*v*UثWbPEvQWQXu]X#qB<1TV*ռkzm|$ː41TUi AԵ UE3@= ~Zy8|+0Xks,7H񚦿<ç'K]Ïl >ҵ+]SMmk,gمh}Cv*UثWb]v*UثWb]c^lfԮ 4&}MG0|=gcڸ$UUP(*ƴ 櫝06;Z}f!ҏX&]v*UثWb]H<]EŦ7SWv:VYQF |銦V6: AoD |x~c*2x`㗽\B7YmXV_>RU]v*UثWb]v*UثWb]yO3Ko ?Ff1v!?%~g>]Eԍv\h_C/}, jCv*UثWb]v*UثWbVnClUIIڂ+lU`?kkN*֍أQxWb]v*Uتż7@AgH([a;)(6qWbT/m>4Let4 ױ;1o@銣7pqV擣l[V1CTku##>=3l>${g*[}ҷ6R{|k5e^۱~.?T6O\Wb]v*UثWb]v*Uث5<|w]Zh=#B{`qTWk|>`<>bԢGݢ[1|Dj=Αۏ, GRkzZtk_ъ:^. dҗU$^P^y/?;? Y9R=)=!A )Ubl]v*UثWb^9qf:Ϙo>KAdec&F~|M1" {O)h6,^hcO[ى( k©bĚakO_֭Y4-u(dG?2*~vMݥ%<+j7TX4U UYmghY9]yhPA貺\=#r8#$E6+ #&FżPUثWb]v*UثWb]K|5/FUmNH[n s'kE}[}Vk3m8.#3cP5d,⋸0K+[ƌ̉0f!EHQs>$1cȽsS|Mq Cuo'D!c@C~lv*UثWb]v*UثWb~6#^-enzNb#w/Gɨ sSγf]]E:\iH+WJUС~u5 Mk r/g VZZk:ШHK ;>qg^ZLܮnHAP'|y7skN.\;$xUS@77Q|K瞚k5?I.#Wsv_l1>NfQzy-9kY^AzU9p6DQ Xv*UثWb]Bi9KeJq<<* n :t8*UEu*2U s}! _/uٯF5ѶVRmgeM"Cq|J\v ,F^iwkykݤqk: !6 *XlA)Wv*UثWb]v*UثVA,@; Ugmߩ1T͞qɩ^IP!VBssd S^b;/OSH'_`{!Kv\b=0.?sx[̚|wqbL|$E^~OfX,cs,QIp#*\,w3*ya-5njT:7BprzstU|B#֔SMC#+B n4zeثWb]̪Uf;s_u |zq\Vz'dj?72,y~[-bMRD 9R@R@YvML[DrNX)%q&ogFPxnGY9]6303e.iڭ:]ZL)$2Jه4Js&˷k/->!ujIc/y,|kX;efo7h>gr&Aз,M!N] FEO.Nrn#Wb]v*UثWb]v*2ëy{ƱEڍw 2B$Z% 'b"?t1iH5/2Eɸ]v*UثWb]v*U"g+ϩJ\! s._YϹR>(MOߘ-.uFADz1-Of;dk_8#s4]Kt}?M[{[dUөI;b<3M?Tƥ~%E@$;7Uz̒NlF P2Oe8;Ӥl!J:6ْ6FBp\zy:X۫Vt/+IGM3'gC<O?idOQBI`d:V*Uث󯚴/%/nJ}%Dy0@{ ɄFhy_|-3<%˸wMGH5ŤƻrxZYzO֛QSFV^F(}R_˞A4yQy8{P7ۡڣn\giD81;t\V=^\m*B9E! QZVx'+/R}P_ty fA'Ol't~/rnݝ崖p)YaC+)AE%D(|GB;ּy{Ͷͩjt5 fA[o r(or;CG 0 _7ZnϹ,鿝o4yF[Fdx)Jf$4]ieZ)1|IN` SmzE:׮*3av;gO2^靊v*UثWb]v*U&O4r7WmK_6oO 9Cs/~f+v*8w&#j2B8@NQwQ/PT>Uͤɦjz78$m,2h4>E_X$ƓXou}aQ]ђ)Uh2cQ}31"sA%sC$X;oL[2gfK[wUa{9a{avV8q&?^t<ŠJ4{y+G*A98O[Lo]L(u$&+]v*UثWb]_5fL+@Osa\H/9?[fƇ{2L$PLO%kSf_'O49ރ7bX_0#x|'y9DcHvCP }Mv*UثWb]v*U.&>GP ghT)"*Q2lTS3?'G*5/|/P`_ѫ |#\z1 ۶K-_F1} ]?{V?0CO[YYuQȉ,δYL2<Ë̺L^@2Ipy[xe~Lw"̽_̚<-*rRDQcTEqErȮ ̲CWb]v*UثWbWϙttHm3'N;P7|9]nauo8)h̯y:/9?ʿ :Ψ B\W,kU\͗۸c|Vm9S_[i3]1KkhYHT&so 4yNԡDiC.yںl^ 8G>c7Vr5̋*`Aw4h29[ F9>anv*&mp}{Sf~ ?oeOC?[p4>s!H%kWE@.2Y8%nHs9;c#̯Gez'ɵ7աHE!"^WOٲqw]:|||qتOI$*?*]W;k 9{l}?A9{v*U~U.M]q0"Ï+!+.bU~<227_GzW 5oֆ4&̍ n_`bf=gie&'eNsWb]v*UثWEA؃KIbHF*6:h n1c<_RK,IE٘mNfxyں$$|ݞ`LZ^~x2^YdR6wޛ;b/caCCѓOqQv\5\T<ۢA匧QlcrP"(}Ov*UثWb]v*U(w\G݊"P**U.n̺LfJzǏ”)0PO;C>-A&b%"8Gq2"*(vR2l3WGg%,Ԓc]9{b3VO1>kO qzruޫ|cN]ԐdHc5ȹ?[wbtǤ_Z>^].tM$HUQYJͻ88Q06ʮXSpqU/< 1VX20P1U\Uثmו8ktNF*ucZ?˒x43X/?4uMC>0G6p+Y$TS-D|,>$N~_~h^hןM5yđ(6G.#mЎG{Ѳ=ت١h)de`{v85Y<_N+k,Zmr ,)!j*]v*UثWb]I<(v0Sɳ]_>C7CS(YuLe'6kثW~xiE'$2~03^Y_tVofCEʜb]v*UثWb]v*U$O&*xt,OO>Lf>v2=.k^ثʯ <#i(]سRm `6b/?P O7׏Q6#e"*UثWb^ kxV F5v*UثWb]v*UثWb]V\4_\lOZٱn^7%dFrRkNH0cfs ''\ԾSPUثWb]v*UA1$p}aͫ=;SI_9`9w韼=0ޑثWb]v*UثWb]v*4}KN .he(h\P*W@}#4?"ӿ&|a[_5Mi*MyT$5eKf-r@, ;v*{0߭nܬb +ऐ(8Dד'}g!/Ւ%Z'G-i^k.&٤iYY6V$ȓmш(&;v*UثWb]v*UثWbg,.u.jv65ʹB'*;("<zd>E1Oæ^\DQM3 шD`M Ʃǖ f@^ثWb]v*UثW?U Tno39JPNńsO~fq26_"\;b79Ђ0@srv*UثWb]v*UثWb^(X~oODDE <**UثWb]v*UثWb]v*UثWbvtbk 3ԒOri-?+hUE *<1VWb]v*UثWb]oS&~V_W}NBkӑQTej"$hVSWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]KރRu?}W]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثW endstream endobj 21 0 obj <>stream hlJAoFNTI.8D0WXD DR&n$ |_Z|λ, |3Z/XVu\wZ\Jlϳⵘo%c g}A๞ 1%x#S}pѩB=Re@*܇-!rsA!  "Ca0B7fHđ㕣e,8 !CT@%(#sht(&+࿀e0RRj!♝> endobj 23 0 obj <> endobj 24 0 obj <>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 25 0 obj <>stream /GS1 gs BT /F1 1 Tf 9.9626 0 0 9.9626 74.0976 715.4644 Tm 0 0 0 rg 0 Tc 0 Tw [(Th)-7(erefore,)-352.7(there)-353.6(is)-346.9(a)-349.7(nontriv)-7.1(ial)-345.3(intera)-10(ction)-346.9(b)-6.5(etween)-352.4(the)-348.3(two)-350.4(para)-8.6(meters)-353.3(\()]TJ /F8 1 Tf 29.864 0 TD (b)Tj /F1 1 Tf .8991 0 TD (and)Tj /F8 1 Tf 1.7982 0 TD (x)Tj /F1 1 Tf .7227 0 TD [(\).)-344.6(In)-350.6(principle)-9.3(,)-341.8(this)-351.2(two-)]TJ -33.284 -1.195 TD [(dim)-8.6(ensional)-369.2(\()]TJ /F8 1 Tf 5.6109 0 TD (b)Tj /F1 1 Tf .5577 0 TD (,)Tj /F8 1 Tf .6089 0 TD (x)Tj /F1 1 Tf .7227 0 TD [(\))-361.2(space)-368.9(of)-362(parame)-9.7(ters)-363.6(shoul)-7.8(d)-359.3(b)0(e)-367.5(explored)-8.7(.)-358.9(I)0(n)-362(this)-368.3(way,)-366.9(we)-360.1(get)-365.3(man)-7.6(y)-359.3(possi)-9(ble)-359.7(type)-7.6(s)-360.5(o)0(f)]TJ -7.5001 -1.2007 TD [(fore)-8.8(st:)-242.3(many)-247.4(small)-243.5(trees,)-252.7(many)-241.7(large)-251.1(trees,)-247(few)-243.3(small)-249.1(trees,)-247(few)-243.3(larg)-9.6(e)-241.6(trees)-246.6(\(see)-243.1(Su)-6.4(ppleme)-8.7(ntary)-243.7(Material)-251.3(and)]TJ T* [(Fig.)-260.7(S2\).)-254.2(The)-254.3(effect)-261.3(of)]TJ /F8 1 Tf 9.1845 0 TD (x)Tj /F1 1 Tf .9731 0 TD (and)Tj /F8 1 Tf 1.7015 0 TD (b)Tj /F1 1 Tf .8081 0 TD [(intervals)-260.9(highly)-254.8(depend)-8.1(s)-252.3(o)0(n)-257.6(the)-257.2(distributio)-8.3(n)-251.2(o)0(f)-253.9(edge)-257(cost)-8.8(s)-252.3(and)-254.5(node)-255.2(pri)-7(zes)-251.7(in)]TJ -12.6672 -1.2007 TD [(the)-245.8(target)-10(ed)-242.3(interact)-10.3(ome,)-241.3(so)-241.7(thes)-8.8(e)-241.6(parame)-9.7(ters)-244.1(will)-242.9(be)-242.3(differ)-9.4(ent)-240.1(for)-245.2(different)-249.5(datasets.)-253.1(For)-242.5(the)-240.2(yeast)-250.3(dataset,)]TJ /F8 1 Tf 42.48 0 TD (x)Tj /F1 1 Tf -42.48 -1.2007 TD [(valu)-7.6(es)-334.6(are)-337.9(tune)-7.6(d)-330.8(betwee)-10.9(n)-330.8([0.005)-6.2(,)-336.1(0.1])-334.7(and)]TJ /F8 1 Tf 17.5895 0 TD (b)Tj /F1 1 Tf .8877 0 TD [(valu)-7.6(es)-334.6(are)-337.9(tuned)-338.4(betwee)-10.9(n)-330.8([1,)-333.9(20].)]TJ /F5 1 Tf 10.959 0 0 10.959 74.0976 631.7856 Tm [(2.5.)-502(Functional)-329.5(annotation)]TJ /F1 1 Tf 9.9626 0 0 9.9626 84.0755 613.8707 Tm [(For)-407.5(funct)-10.3(ional)-409.5(enrichment)-416.7(analysi)-9.9(s,)-406.4(the)-410.9(BINGO)-414.9(plug-in)-411.2(\()-82.4(Maer)-10.6(e)-406.6(e)0(t)-404.4(al.,)-410.9(2005\))-409.8(of)-407.5(Cytosc)-9.3(ape)-409.9(\(Shann)-7.5(on)]TJ -1.0015 -1.2007 TD [(et)-267.8(al.,)-274.3(2003\))-267.6(was)-271(used.)-268.2(Th)-7(e)-264.3(p-value)-275.4(signica)-9.9(nce)-267.6(threshol)-10.9(d)-262.5(o)0(f)-271(0.05)-264.4(was)-271(used,)-273.9(which)-268.4(is)-267.2(corr)-8.8(ected)-268(for)-268(mul)-8.6(tiple)]TJ T* [(hy)-7.2(pothesis)-380(testing,)-381.2(and)-379.7(all)-379.5(yeast)-381.2(proteins)-380.8(were)-382.4(used)-381.6(as)-374.4(the)-376.7(backgr)-10.1(ound)-378.6(set)-377.9(for)-376.1(the)-376.7(yeast)-381.2(data)-9.4(set.)-378.3(For)-379.1(the)]TJ T* [(hu)-7.2(man)-292.1(dataset,)-296.6(the)-297.1(functional)-300.3(enrichment)-297.1(is)-295.7(performed)-298.7(by)-291.7(usin)-7(g)-285.3(all)-294.1(huma)-8.4(n)-291(proteins)-295.4(as)-294.7(background)-297.7(set)-8(.)-284.9(All)]TJ T* [(networ)-9.3(k)-336.5(visualiza)-10.3(tions)-334.9(were)-342.6(performed)-344.2(in)-334.3(Cytoscape)-345.3(\(Shann)-7.6(on)-331.6(et)-336.1(al.,)-336.9(2003\).)]TJ /F2 1 Tf 10.959 0 0 10.959 257.6125 524.1826 Tm [(3.)-496.7(RESULTS)]TJ /F5 1 Tf -16.7456 -1.6347 TD [(3.1.)-502(Practical)-330.2(advantages)-328.7(of)-331.2(the)-334.3(message-passing)-331.7(solution)-326(for)-334.2(biological)-331.4(networks)]TJ /F1 1 Tf 9.9626 0 0 9.9626 84.0755 488.3526 Tm [(Previo)-10.3(us)-446.6(wor)-8.2(k)-450.3(has)-449.1(show)-8.2(n)-450.3(that)-454.2(the)-450.7(message)-10.9(-passin)-8.6(g)-450.3(approximat)-10.8(ion)-448.9(is)-455(faster)-454.2(than)-451.5(the)-456.4(branch-a)-9.7(nd-cut)]TJ -1.0015 -1.2007 TD [(algo)-7.6(rithm)-413.2(and)-408.1(typical)-11.5(ly)-408.3(nds)-407.5(a)-412.3(compara)-10.5(ble)-410.9(value)-414.2(for)-410.3(the)-405.2(o)-6.5(bjective)-412.4(functi)-8.2(on.)-411.6(This)-410.8(comparison)-419(was)-413.2(per-)]TJ T* [(formed)-372.3(on)-365.7(a)-366.7(benchmar)-11.3(k)-359.3(set)-366.5(that)-368.9(is)-364(not)-369.2(related)-371(to)-362.8(biologi)-7.9(cal)-367.1(data)-367.9(\(Bailly-Bec)-12.7(het)-365.3(et)-370.3(al.,)-365.3(2010a\).)-367.2(Since)-367.9(the)]TJ T* [(mes)-8.8(sage-pas)-10.1(sing)-251.7(appro)-7.6(ach)-250.6(only)-256.2(approximat)-10.8(es)-249.2(the)-251.5(exact)-256.6(solu)-7(tion)-247.6(found)-256.2(by)-251.9(the)-251.5(branc)-9.4(h-and-cut)-256.2(algori)-8.2(thm,)-253.7(we)]TJ T* [(com)-7.6(pared)-282.5(the)-280(p)-6.5(erformanc)-10.3(e)-281.4(o)0(f)-276.7(these)-284.5(two)-282.1(algori)-8.2(thms)-278(o)-6.5(n)-273.9(phospho)-6.5(prot)-7.8(eomic)-281.1(and)-282.9(transcr)-11.1(iptional)-286.4(data)-282.5(from)-283.7(the)]TJ T* [(yeast)-341.4(phero)-7.6(mone)-338.4(response.)]TJ 1.0015 -1.195 TD [(We)-307.5(perf)-8.8(ormed)-307(an)-304.9(ini)-7.8(tial)-303.3(anal)-9.4(ysis)-304.1(to)-305.9(determ)-10.7(ine)-308.4(the)-302.7(appro)-7.6(priate)-311.6(parama)-9.7(ter)-304.7(setti)-9.4(ngs.)-305.5(In)-305.1(the)-308.4(branch-a)-9.7(nd-cu)-7.6(t)]TJ -1.0015 -1.2007 TD [(algo)-7.6(rithm,)-493.2(the)-496.2(size)-494.3(of)-492.9(the)-490.5(networ)-9.3(k)-490.2(i)0(s)-494.9(controlle)-9.3(d)-490.2(only)-495.2(by)-490.9(the)-490.5(beta)-498.8(parame)-9.8(ter.)-492.9(In)-492.9(the)-490.5(message)-10.9(-pas)-8(sing)]TJ T* [(algo)-7.6(rithm,)-248.5(there)-251.1(is)-244.5(a)-241.6(secon)-8.6(d)-245.5(parameter)-12.9(,)-239.4(calle)-9(d)-245.5(depth,)-247.7(that)-243.7(can)-250.6(also)-247.8(be)-242.3(used)-250.7(to)-243.3(cont)-7.6(rol)-246(the)-245.8(size)-243.9(of)-248.2(the)-245.8(resulting)]TJ T* [(tre)-8.8(e.)-253.3(Dep)-8(th)-254.7(\(D)-7.4(\))-253.1(repr)-8.8(esents)-263.7(the)-257.2(max)-7.6(imum)-257.6(allow)-9.4(ed)-259.4(distance)-262.9(betwee)-10.9(n)-256.8(the)-257.2(far)-8(thest)-257(nod)-8(e)-252.9(i)0(n)-260.4(the)-257.2(tree)-261.7(and)-260.2(the)-262.9(root)]TJ T* [(no)-7.2(de.)-288.2(Based)-297.8(on)-291.7(these)-295.9(observat)-9.9(ions,)-291.9(we)-291.8(tes)-8(ted)-291.4(several)-295.5(dept)-7.6(h)-291(values)-296.6(on)-286.1(the)-297.1(yeast)-295.9(interactome)-302.5(and)-288.6(found)-296(that)]TJ T* [(dept)-7.6(h)-308.1(value)-311.7(equal)-311.7(to)-305.9(20)-308.8(produc)-8.3(es)-311.8(the)-308.4(best)-310.4(objective)-316.4(functi)-8.2(on)-308.8(value)-311.7(in)-305.9(the)-308.4(PCST)-313.3(runs)-313.5(on)-303.1(yeast)-312.9(data)-9.4(set)-309.6(\(see)]TJ T* [(Fig.)-311.9(S3a\).)-313.7(To)-308.6(check)-316.5(the)-308.4(robus)-7(tness)-312.3(of)-305.1(the)-314.1(message)-10.9(-passin)-8.5(g)-308.1(algorithm)-312.7(we)-314.5(added)-309(n)-6.5(oise)-310.4(to)-305.9(edge-)-9.4(weights)-313.7(and)]TJ T* [(re-)-8(ran)-262.1(it)-263.1(\(see)-265.9(Fig.)-260.7(S3b\).)-266.4(We)-261.9(refer)-269.4(to)-260.4(the)-262.9(solutions)-267.9(of)-259.6(thes)-8.8(e)-258.6(nois)-7(y)-256.8(input)-9.3(s)-258(a)0(s)-260.6(subopt)-8.5(imal)-264.3(solu)-7(tions.)-261.3(The)-265.7(overlap)]TJ 0 -1.195 TD [(betwee)-10.9(n)-296.7(subopt)-8.5(imal)-298.4(solu)-7(tions)-300.7(and)-300(the)-297.1(origina)-8.9(l)-293.7(solu)-7(tion)-298.8(is)-295.7(still)-300.6(very)-302.7(high)-301.7(up)-297.4(to)-294.5(a)-298.5(nois)-7(e)-292.8(valu)-7.6(e;)-296.3(theref)-9.2(ore,)-302.3(the)]TJ 0 -1.2007 TD [(solu)-7(tion)-338.6(is)-329.8(robus)-7(t)-333.6(t)0(o)-334.3(nois)-7(e)-332.6(o)0(n)-337.3(the)-336.9(yeast)-335.7(phero)-7.6(mone)-338.4(data.)]TJ 1.0015 -1.2007 TD [(Hav)-8(ing)-255.4(identied)-256.9(a)-258.6(suitable)-258.2(range)-259.7(for)-256.6(the)-257.2(parameters,)-265.6(we)-251.9(com)-7.6(pared)-259.7(the)-251.5(mes)-8.8(sage-pas)-10.1(sing)-257.4(algorithm)-261.4(to)-254.7(the)]TJ -1.0015 -1.2007 TD [(branc)-9.4(h-and)-7.6(-cut)-499(algorithm)-500.4(on)-496.6(the)-501.9(original)-501.8(undirected)-504.2(yeast)-500.7(intera)-10(ctome.)-497.7(As)-501.7(mentioned)-503.2(previous)-8.1(ly,)-499.7(the)]TJ T* [(mes)-8.8(sage-pas)-10.1(sing)-297.2(algo)-7.6(rithm)-299.4(n)-6.4(ds)-298.6(a)-298.5(solution)-300.1(to)-300.2(the)-302.7(PCST)-301.9(problem)-305.6(in)-294.5(a)-304.1(computatio)-11.6(nally)-301.3(very)-297(eff)-8(ective)-305.7(way.)]TJ T* [(Fo)-6.4(r)-440.9(example,)-444.2(the)-445(branc)-9.4(h-and-cut)-443.9(algo)-7.6(rithm)-441.6(\(Lju)-7.6(bic)-439.3(et)-444.2(al.,)-445(2006\))-444(takes)-443.8(931)-440.5(secon)-8.6(ds)-440.9(to)-442.5(reach)-443.6(the)-445(exact)]TJ T* [(solu)-7(tion)-310.2(with)-314.1(an)-310.6(ob)-7.2(jective)-314.9(value)-317.4(of)-310.8(2.2123,)-311.9(while)-316.7(the)-314.1(message)-10.9(-passin)-8.6(g)-308.1(algori)-8.2(thm)-310.2(reports)-316.6(a)-309.8(solu)-7(tion)-310.2(in)-311.6(237)]TJ T* [(secon)-8.6(ds)-270.2(with)-274.3(an)-265.1(obje)-7.6(ctive)-274.7(value)-271.9(2.2178.)-272(Critic)-10(ally,)-266.8(we)-274.7(nd)-269(that)-272.1(the)-268.6(overlap)-275.4(of)-271(the)-268.6(nodes)-274.3(betwee)-10.9(n)-268.2(these)-273.1(two)]TJ 0 -1.195 TD [(solu)-7(tions)-289.4(is)-284.3(98.5)-8.4(%.)-282.7(Th)-7(is)-284.3(result)-293.9(shows)-289(that)-289.2(almost)-289.7(the)-291.4(same)-290.2(solu)-7(tion)-287.4(is)-284.3(obta)-7.6(ined)-286.4(by)-286.1(bo)-7.2(th)-283.1(algo)-7.6(rithms,)-290.3(but)-289.6(the)]TJ 0 -1.2007 TD [(mes)-8.8(sage-pas)-10.1(sing)-371.2(approach)-377.6(is)-369.7(almost)-369.4(four)-371.2(time)-8.2(s)-366.2(faster)-374.6(than)-371.8(the)-371(branc)-9.4(h-and-cut)-375.7(approach)-377.6(\(Table)-371.2(S1)-6.4(\).)-367.3(The)]TJ T* [(dif)-7(ference)-352.2(in)-345.7(speed)-355.7(becomes)-356.8(critical)-354.5(when)-350.2(exploring)-351.9(the)-348.3(space)-351.8(of)-350.6(parame)-9.7(ters)-346.5(or)-350.6(testing)-352.3(the)-348.3(robustne)-8.1(ss)-345.3(of)]TJ T* [(solu)-7(tions.)]TJ 1.0015 -1.2007 TD [(To)-365.5(analyze)-373.7(the)-365.3(effects)-371.4(of)-362(the)-365.3(dir)-7(ectionalit)-9.7(y)-365(i)0(n)-362.8(the)-365.3(solution,)-368.8(we)-365.7(added)-371.6(directed)-371.8(edges)-367.1(from)-369(enzymes)-368.2(to)]TJ -1.0015 -1.2007 TD [(their)-462.7(substra)-8.6(tes)-457.6(using)-457.3(the)-456.4(kinase)-461.7(and)-453.6(phophat)-9.9(ase)-456.6(intera)-10(ction)-455(networ)-9.3(k)-456(i)0(n)-453.8(Breitkreut)-11.1(z)-452.1(e)0(t)-461.3(al.)-456(\(2010\).)-458.5(The)]TJ T* [(algo)-7.6(rithm)-327.8(is)-324.2(able)-322.4(to)-323(n)-6.4(d)-319.4(a)-321.2(sma)-8.8(ller)-325.3(network)-328.8(that)-323.3(still)-329(include)-8.7(s)-320.6(the)-325.5(same)-324.3(nu)-7.2(mber)-323.3(of)-322.2(termin)-11.7(als)-321(as)-323.2(whe)-8(n)-319.4(only)]TJ T* [(the)-331.2(transcr)-11.1(iption)-331.5(factor)-9.2(DNA)-333.5(edges)-332.9(were)-331.2(direct)-10(ed.)-328.1(In)-327.9(these)-335.7(two)-327.7(exampl)-8.7(es,)-329.2(havi)-7.6(ng)-325.9(more)-334.7(directed)-331.9(edges)-332.9(in)]TJ 0 -1.195 TD [(the)-314.1(starting)-315.2(interact)-10.3(ome)-309.2(resu)-8(lts)-304.9(in)-311.6(more)-311.9(compact)-318.6(PCST)-313.3(solutions)-313.4(that)-312(connec)-9.9(t)-305.1(the)-308.4(sam)-8.8(e)-304.2(n)0(u)-7.2(mber)-311.9(of)-305.1(prot)-7.8(ein)]TJ 0 -1.2007 TD [(ter)-8.8(minals)-238.5(u)-6.5(sing)-240.3(fewer)-242.9(intermed)-9.3(iate)-239.8(nod)-8(es)-237.8(\(Table)-246(S1\).)-237.2(Th)-7(ese)-240.4(more)-243.7(compact)-244.6(trees)-240.9(are)-241.2(likel)-8.2(y)-239.8(t)0(o)-237.6(b)0(e)-236.6(mor)-7.8(e)-235.9(usefu)-8.8(l)]TJ T* [(for)-279.4(gener)-9.4(ating)-278.6(testab)-9.2(le)-273.5(biologi)-7.9(cal)-276.1(hy)-7.2(pothesis,)-283.6(since)-278.8(the)-280(Steiner)-283.1(nodes)-279.9(that)-277.8(they)-280.7(include)-281.9(are)-281(the)-274.3(ones)-279.2(that)-283.5(are)]TJ T* [(mos)-7(t)-430.3(constra)-9.1(ined)-434.4(by)-434(the)-433.6(experim)-11.5(entally)-438.3(derived)-434.8(terminal)-12.1(s.)-429.1(Fu)-6.4(rther,)-433.8(by)-434(adding)-435.9(direct)-10(ions)-433.8(between)-438.5(tran-)]TJ T* [(script)-9.4(ion)-363.6(factors)-363.9(to)-362.8(targets)-364.7(and)-362.6(enzyme)-366.3(to)-362.8(substra)-8.6(te)-358.9(intera)-10(ctions,)-366.3(we)-360.1(are)-360.7(able)-367.9(to)-357.1(obta)-7.6(in)-357.1(condi)-8.4(tion-s)-7.6(pecic)]TJ T* [(tra)-8.8(nscriptio)-8.7(n)-330.8(factor)-9.2(s)-332(and)-339.8(compact)-341.3(networ)-9.3(ks.)]TJ /F2 1 Tf 0 67.0005 TD [(12)-7.2(8)]TJ 34.5644 0 TD [(TUNCBA)-12.7(G)-334.4(E)0(T)-335.3(AL.)]TJ ET endstream endobj 26 0 obj <> endobj 27 0 obj <>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 28 0 obj <>stream /GS1 gs BT /F5 1 Tf 10.959 0 0 10.959 107.6031 714.7841 Tm 0 0 0 rg 0 Tc 0 Tw [(3.2.)-496.9(The)-430.6(PCSF)-430.6(approach)-425.6(reveals)-434.4(parallel)-425.6(working)-430.2(pathways)-432(in)-429.5(addition)-428.3(to)-429.5(hidden)-427.7(individual)]TJ 0 -1.0864 TD [(proteins)-331.9(or)-330.7(genes)-333.5(in)-331.2(yeast)-335.2(pheromone)-329.6(response)]TJ /F1 1 Tf 9.9626 0 0 9.9626 117.5811 679.7478 Tm [(High-thr)-8.1(oughput)-315.4(experimental)-320.3(methods)-316.2(like)-312(mass-s)-9.7(pectromet)-11.9(ry)-305.1(are)-315.1(capab)-9.2(le)-307.7(of)-310.8(simulta)-8.7(neously)-312.7(detect)-9.8(ing)]TJ -1.0015 -1.2007 TD [(change)-9.9(s)-246.6(i)0(n)-254.7(many)-253.1(disti)-7.6(nct)-251.5(biologi)-7.9(cal)-253.3(processe)-10.1(s)-252.3(that)-255.1(will)-254.3(not)-249.7(be)-253.7(connec)-9.9(ted)-251.5(by)-251.9(physical)-261.1(interactions)-11.7(.)-250.8(Howeve)-10.3(r,)]TJ T* [(the)-359.7(PCST)-358.8(appro)-7.6(ach)-364.4(searches)-364.7(for)-359.1(a)-355.4(tre)-8.8(e)-355.4(structu)-10.1(re)-358.1(in)-357.1(the)-359.7(interact)-10.3(ome)-360.4(that)-357.5(connec)-9.9(ts)-358.3(as)-357.3(man)-7.6(y)-353.6(o)0(f)-362(the)-359.7(experi-)]TJ T* [(mental)-392.8(data)-390.7(as)-385.8(it)-388.3(can.)-387.5(As)-387.9(a)-389.5(result,)-391(it)-382.6(will)-390.8(either)-391.2(have)-393.6(to)-385.6(exclude)-394.7(some)-390.8(of)-384.8(the)-388.1(data)-390.7(that)-385.9(relat)-9.2(e)-383.8(t)0(o)-385.6(disti)-7.6(nct)]TJ T* [(biologi)-7.9(cal)-304.5(process)-309.2(or)-299.4(add)-305.7(spurio)-10.5(us)-298.6(edges)-310.2(to)-300.2(forc)-8.8(e)-298.5(thes)-8.8(e)-298.5(data)-311(to)-300.2(connec)-9.9(t)-299.4(t)0(o)-305.9(the)-302.7(tree.)-307.6(The)-305.5(main)-307(advantage)-312.7(of)]TJ T* [(the)-268.6(PCSF)-272.9(appro)-7.6(ach)-273.3(over)-268.6(PCST)-279.2(is)-267.2(that)-272.1(PCSF)-272.9(does)-273.5(not)-266.8(forc)-8.8(e)-270(the)-268.6(system)-276.8(to)-266.1(be)-270.8(connec)-9.9(ted)-268.6(in)-271.7(a)-270(single)-274.8(network,)]TJ 0 -1.195 TD [(and)-334.1(it)-337.1(can)-335.9(auto)-7.6(matically)-339.8(separ)-10.6(ate)-333(mul)-8.6(tiple)-338.2(pathways.)]TJ 1.0015 -1.2007 TD [(We)-290.4(tested)-293.7(the)-285.7(PCSF)-295.6(algorithm)-295.6(using)-292.3(data)-288.2(from)-289.4(the)-291.4(yeast)-295.9(pheromon)-7.7(e)-287.1(respon)-9.5(se,)-289.4(which)-291.1(we)-291.8(had)-288.6(previous)-8.1(ly)]TJ -1.0015 -1.2007 TD [(analyzed)-494(using)-485.8(the)-490.5(prize-)-9.2(collecting)-490.7(Steiner)-493.6(tree)-489.4(appro)-7.6(ach.)-484.2(Th)-7(e)-486.3(data)-487.4(consist)-493(of)-481.5(phospho)-6.5(prot)-7.8(eomic)-486(and)]TJ T* [(transcrip)-9.7(tional)-418.7(change)-9.9(s)-411.7(induc)-8.4(ed)-413(by)-416.9(mating)-419.4(pheromon)-7.7(e,)-412.7(and)-419.5(the)-416.6(networ)-9.3(k)-410.5(i)0(s)-415.2(enriche)-9.7(d)-410.5(w)0(i)-8.2(t)0(h)-414(directed)-423(tran-)]TJ T* [(scription)-293.2(factor)-9.2(target)-289.6(and)-288.6(kina)-7.6(se/phosph)-8.1(atases)-10.1(ubstrate)-291.5(reac)-10.4(tions.)-289.7(The)-288.4(edge)-291.2(costs)-289.6(of)-288(the)-285.7(intera)-10(ctome)-286.8(wer)-10(e)]TJ T* [(compute)-9.5(d)-427.6(a)0(s)-431.3(the)-427.9(negat)-10.1(ive)-427.9(log)-431.8(of)-430.3(the)-427.9(intera)-10(ction)-432.2(probabiliti)-8.9(es,)-431.7(and)-430.9(node)-431.6(prizes)-435.2(were)-433.6(obtaine)-8.7(d)-427.6(from)-431.6(the)]TJ T* [(scheme)-339(deta)-9.4(iled)-334.7(in)-334.3(Huang)-339.6(and)-334.1(Fraen)-8.6(kel)-336.9(\(2009\).)-339(To)-331.4(expl)-7.6(ore)-336.1(the)-336.9(space)-334.7(of)-339.2(solutions,)-336.6(we)-337.3(tune)-7.6(d)-330.8(the)]TJ /F8 1 Tf 39.8111 0 TD (x)Tj /F1 1 Tf 1.0528 0 TD (and)Tj /F8 1 Tf 1.7811 0 TD (b)Tj /F1 1 Tf -42.645 -1.2007 TD [(parame)-9.7(ters)-295.3(betwee)-10.9(n)-296.7([0.005)-6.2(,)-290.6(0.1])-300.6(and)-294.3([1,)-299.8(20],)-294.9(respect)-10.9(ively.)-296(Th)-7(e)-292.8(minimum)-10.1(,)-296.3(maximum)-9.1(,)-290.6(and)-300(average)-304.7(size)-300.8(and)]TJ 0 -1.195 TD [(numb)-6.6(er)-324(of)-327.9(trees)-332(in)-328.7(the)-331.2(construc)-9.9(ted)-331.2(PCSFs)-331.7(are)-326.5(extr)-9.6(acted)-330.6(for)-330.6(each)-332.8(\()]TJ /F8 1 Tf 27.0244 0 TD (x)Tj /F1 1 Tf .7227 0 TD (,)Tj /F8 1 Tf .5747 0 TD (b)Tj /F1 1 Tf .552 0 TD [(\))-327.1(pair,)-334.3(and)-328.4(the)-331.2(distributio)-8.3(n)-325.1(o)0(f)-327.9(thes)-8.8(e)]TJ -28.8738 -1.2007 TD [(values)-336.5(along)]TJ /F8 1 Tf 5.4515 0 TD (x)Tj /F1 1 Tf 1.0471 0 TD [(p)-6.5(arameter)-336.5(is)-329.8(plotted.)-334.5(We)-330.2(looked)-333.5(for)-330.6(a)-326.9(solu)-7(tion)-327.2(in)-328.7(a)-326.9(regi)-9.6(on)-325.9(whe)-8(re)-329.7(the)-325.5(numb)-6.6(er)-329.7(of)-327.9(trees)-337.7(and)]TJ -6.4986 -1.2007 TD [(average)-304.7(size)-300.8(of)-293.7(the)-297.1(trees)-303.5(in)-294.5(the)-297.1(fore)-8.8(st)-295.7(are)-298.1(closest)-301.3(to)-294.5(each)-304.3(other.)-300.9(By)-296.5(these)-301.6(criteria,)-302.9(the)-297.1(best)-299(solu)-7(tion)-298.8(is)-295.7(found)]TJ T* (when)Tj /F8 1 Tf 2.4925 0 TD (x)Tj /F6 1 Tf 1.0528 0 TD (=)Tj /F1 1 Tf .8877 0 TD [(0.025)-327.8(and)]TJ /F8 1 Tf 4.3533 0 TD (b)Tj /F6 1 Tf .8877 0 TD (=)Tj /F1 1 Tf .8877 0 TD [(13)-325.9(\(Fig.)-326.1(S4\).)-322.5(We)-330.2(note)-326.3(that)-329(in)-323(order)-328.2(to)-328.7(explore)-326.6(thes)-8.8(e)-321.2(para)-8.6(meters,)-331(we)-325.9(construc)-9.9(ted)]TJ -10.5617 -1.2007 TD [(400)-235.6(solutio)-9.1(ns)-230.3(to)-237.6(the)-234.5(PCST)-239.3(probl)-8.6(em.)-234.8(This)-240.1(number)-239.5(of)-236.8(calculat)-10.1(ions)-234.6(is)-233.1(only)-239.1(practi)-10(cal)-236.2(using)-235.4(the)-240.2(message)-10.9(-passing)]TJ T* [(algori)-8.2(thm,)-333.3(but)-335.1(not)-335.1(with)-342.6(the)-331.2(int)-7.8(eger)-338.7(linear-prog)-12(ramming)-8.3(based)-338.6(appro)-7.6(aches.)]TJ 1.0015 -1.2007 TD [(The)-373.8(soluti)-8.4(on)-371.4(to)-374.2(PCSF)-375.3(problem)-379.6(places)-378.1(disti)-7.6(nct)-371(funct)-10.3(ional)-375.3(classes)-381.2(in)-374.2(seperate)-383.4(subtrees.)-381.4(In)-373.4(this)-374(solution,)]TJ -1.0015 -1.2007 TD [(there)-364.9(are)-366.3(six)-364.7(trees,)-372.2(each)-366.9(contain)-8.7(ing)-363.6(more)-363.2(than)-366.1(10)-365.7(nodes.)-365.7(In)-367.7(Figure)-368.8(2,)-359.6(each)-366.9(tree)-369.9(is)-364(labeled)-369(with)-365.3(its)-367.5(corre-)]TJ 0 -1.195 TD [(sponding)-300.3(path)-7.6(way.)-298.6(Small)-298.4(subt)-7(rees)-300(such)-301.9(as)-294.7(T)]TJ 7.4718 0 0 6.641 287.0928 415.0487 Tm (36)Tj 9.9626 0 0 9.9626 301.2661 416.7495 Tm [(are)-298.1(enriche)-9.7(d)-296.7(i)0(n)-294.5(speci)-11.3(c)-292.8(biologi)-7.9(cal)-298.8(processe)-10.1(s,)-298.2(including)-301.5(the)]TJ -19.4389 -1.2007 TD [(protei)-8.2(n)-484.5(kina)-7.6(se)-488.2(C)-494.9(\(PKC\))-493.6(pathwa)-9.1(y,)-490.5(actin)-490.9(organ)-7.6(ization,)-495.6(protei)-8.2(n)-490.2(folding)-490.8(and)-493.5(kinetoc)-8.7(hore,)-490.9(and)-493.5(DNA)-492.1(and)]TJ T* [(chromati)-9.3(n)-370.7(path)-7.6(ways,)-374.5(while)-379.2(larger)-379.1(trees)-377.5(contain)-378.6(multipl)-8.5(e)-372.4(processe)-10.1(s.)-372.2(For)-373.4(exampl)-8.7(e,)-372.8(the)-376.7(largest)-376.1(subt)-7(ree,)-372.4(T)]TJ 7.4718 0 0 6.641 531.7227 391.181 Tm (1)Tj 9.9626 0 0 9.9626 535.4645 392.8251 Tm (,)Tj -42.9466 -1.2007 TD [(contain)-8.7(s)-474.3(the)-473.5(phero)-7.6(mone)-475(core)-475.2(mitog)-7.2(en-activat)-13.6(ed)-475.6(protein)-475.6(kina)-7.6(se)-471.1(\()-88.1(MAPK\))-481.4(pathway)-476.5(with)-479.1(CDC28-)-8.5(related)]TJ T* [(protei)-8.2(ns,)-316.1(and)-317.1(the)-319.8(secon)-8.6(d)-319.4(largest)-324.9(one,)-317.4(T)]TJ 7.4718 0 0 6.641 265.4929 367.2566 Tm (3)Tj 9.9626 0 0 9.9626 269.2346 368.9007 Tm [(,)-319.1(contain)-8.7(s)-314.9(transcr)-11.1(iption)-320.2(and)-317.1(transpor)-10.1(t)-316.5(proce)-9.4(sses)-321.4(\(Fig.)-320.4(2\).)-316.9(There)-322.2(are)]TJ -16.2238 -1.2007 TD [(two)-282.1(differ)-9.4(ent)-280(yeast)-284.5(MA)-7.4(PK)-283.5(pathwa)-9.1(ys;)-279.4(the)-285.7(pheromon)-7.7(e-induce)-10.5(d)-279.6(M)0(A)-7.4(P)0(K)-277.8(and)-282.9(the)-285.7(PKC)-283.3(path)-7.6(ways)-283.1(\(Buehr)-9.3(er)-284.1(and)]TJ T* [(Errede,)-478.9(1997;)-473.2(Zarzo)-9.2(v)-473.1(e)0(t)-472.7(al.,)-473.5(1996\).)-472.8(Th)-7(e)-469.2(PCSF)-477.7(algori)-8.2(thm)-469.5(corr)-8.8(ectly)-473.8(separat)-10.9(es)-471.1(these)-478(two)-475.6(pathwa)-9.2(ys)-469.3(into)]TJ T* [(different)-414.5(trees.)-412(The)-407.9(largest)-415.9(tree)-409.7(in)-408.3(size,)-409.3(T)]TJ 7.4718 0 0 6.641 281.1968 331.37 Tm (1,)Tj 9.9626 0 0 9.9626 290.8346 333.0141 Tm [(cont)-7.6(ains)-407.1(phero)-7.6(mone-ind)-10.5(uced)-405(MA)-7.4(PK)-408.7(pathwa)-9.2(y,)-405.2(but)-409.1(the)-405.2(PKC)]TJ -18.3919 -1.195 TD [(pathwa)-9.1(y)-239.8(i)0(s)-244.5(located)-243.8(in)-243.3(T)]TJ 7.4718 0 0 6.641 200.6362 319.4078 Tm (3)Tj 9.9626 0 0 9.9626 204.3779 321.1086 Tm [(.)-245.1(While)-247(the)-240.1(former)-249.1(one)-243.1(induc)-8.4(es)-243.5(cells)-241.7(to)-243.3(differ)-9.4(entiate)-246.6(and)-243.1(be)-242.3(prepa)-9.4(red)-245.1(for)-239.6(mati)-8.2(ng,)-240.9(the)]TJ -9.7138 -1.2007 TD [(latter)-337.1(one)-339.8(is)-335.5(involved)-337.8(in)-334.3(cel)-8.6(l)-333.6(integrity)-340.3(and)-334.1(new)-338.1(cel)-8.6(l-wall)-339.2(synthesi)-10.1(s.)]TJ 1.0015 -1.2007 TD [(The)-277(core)-281.7(phero)-7.6(mone)-281.5(resp)-8(onse)-279.2(pathwa)-9.1(y)-273.9(com)-7.6(ponent)-282.3(in)-277.4(T)]TJ 7.4718 0 0 6.641 341.9716 295.5401 Tm (1)Tj 9.9626 0 0 9.9626 348.4912 297.1842 Tm [(include)-8.7(s)-275.1(the)-280(STE2)-286.4(receptor.)-286(In)-276.6(this)-282.9(subtree,)-282.7(the)]TJ -24.1791 -1.2007 TD [(STE2)-7.6(-GPA1-FU)-8.9(S3)-353.6(interact)-10.3(ion)-352.2(is)-352.6(in)-357.1(the)-354(core)-355.7(of)-350.6(phero)-7.6(mone)-355.5(resp)-8(onse.)-353.5(In)-356.3(addition,)-358(the)-354(MA)-7.4(P)-347.1(k)-6.5(inase)-352.8(FUS3)]TJ T* [(activa)-9.8(tes)-446.2(several)-454.8(transcrip)-9.7(tion)-446.7(factor)-9.2(s,)-446.2(such)-449.9(as)-442.7(STE1)-7.6(2,)-445(DIG1,)-451.4(and)-447.9(DIG2,)-451.4(for)-450.1(the)-445(expre)-9.4(ssion)-447.1(of)-447.4(mating)]TJ T* [(related)-251.5(genes.)-248(T)]TJ 7.4718 0 0 6.641 171.1559 259.6535 Tm (1)Tj 9.9626 0 0 9.9626 177.2787 261.2975 Tm [(cont)-7.6(ains)-242.1(DNA)-8.4(-replicati)-10.9(on)-240.5(prot)-7.8(eins)-242.1(and)-248.8(cell-cycle)-254.4(proteins)-249.9(associated)-250.3(with)-245.8(CDC28)-250.5(as)-243.5(well.)]TJ -6.9937 -1.2007 TD [(Here,)-303.1(the)-302.7(connec)-9.9(tion)-298.8(betwee)-10.9(n)-296.7(the)-302.7(MAP)-303.3(kinase)-302.3(path)-7.6(way)-298.2(in)-300.2(the)-302.7(phero)-7.6(mone)-298.6(core)-304.5(and)-300(the)-302.7(CDC28-)-8.5(assoc)-9.8(iated)]TJ T* [(subnetw)-9.3(ork)-260.3(is)-255.9(const)-9.6(ructed)-263.3(through)-260.5(the)-262.9(interact)-10.3(ion)-255.4(betwee)-10.9(n)-256.8(FAR1)-267(and)-260.2(CDC28.)-262.2(FAR1)-267(is)-255.9(a)-258.6(direct)-266(inhibitor)-264.6(of)]TJ 0 -1.195 TD [(CDC28/)-9.3(CLN2)-318.8(comple)-8.7(x)-308.1(and)-317.1(functi)-8.2(ons)-310.8(in)-317.3(orienting)-320.5(cell)-313.7(pola)-7.6(rization.)-316.2(Th)-7(is)-312.8(associa)-10.2(tion)-315.9(blocks)-317.6(the)-314.1(cell-cycl)-12.9(e)]TJ 0 -1.2007 TD [(progress)-8.5(ion.)-244.4(FUS3)-244.4(phospho)-6.5(ryl)-7(ates)-243.9(FAR1,)-250.3(and)-243.1(only)-244.8(phospho)-6.5(rylate)-10(d)-239.8(FAR1)-249.9(can)-244.9(associa)-10.2(te)-239.4(with)-245.8(CDC)-10(28/CLN2)]TJ T* [(comple)-8.7(x.)-308.4(All)-313.3(these)-312.9(interact)-10.3(ions)-308.6(and)-311.4(thes)-8.8(e)-309.8(connecte)-10.3(d)-308.1(pathwa)-9.1(ys)-310(are)-309.4(corr)-8.8(ectly)-314.5(located)-312.1(int)-7.8(o)-308.1(the)-308.4(sam)-8.8(e)-309.8(subtree.)]TJ 1.0015 -1.2007 TD [(The)-277(algori)-8.2(thm)-276(correctly)-283.5(iden)-7.6(ties)-279(SLT2)-7.6(,)-273.5(which)-279.7(was)-282.3(not)-272.5(dete)-9.4(cted)-276.8(in)-277.4(the)-280(phospho)-6.5(proteomic)-283.2(data,)-277.2(as)-277.7(a)-275.7(k)-6.5(ey)]TJ -1.0015 -1.2007 TD [(node)-312.1(in)-311.6(regulat)-10.7(ing)-312.3(new)-315.3(cell-wa)-10.7(ll)-308.6(synt)-7(hesis.)-312.7(SLT2)-314.9(is)-312.8(a)-309.8(serine/)-11.9(threonine)-319.5(MAP)-314.7(kinase)-313.7(act)-8.6(ivated)-315.3(in)-311.6(a)-309.8(casc)-9.6(ade)]TJ T* [(starting)-286.8(with)-285.7(PKC.)-289.4(The)-282.7(phospho)-6.5(proteom)-9.7(ic)-284.9(data)-282.5(are)-286.7(not)-283.9(sufcien)-9.1(t)-282.4(for)-279.4(the)-285.7(algo)-7.6(rithm)-282.3(to)-283.1(pick)-286.4(up)-280.4(the)-285.7(upst)-7(ream)]TJ T* [(pathwa)-9.1(y.)-291.4(Howeve)-10.3(r,)-293.3(in)-294.5(T)]TJ 7.4718 0 0 6.641 205.7385 152.0504 Tm (3)Tj 9.9626 0 0 9.9626 209.4803 153.6945 Tm [(,)-296.3(the)-291.4(algo)-7.6(rithm)-299.4(links)-295.1(SLT2)-297.8(to)-294.5(several)-301.2(transcr)-11.1(iption)-297.4(factors)-301.3(that)-294.9(mostly)-299.3(function)-299.9(in)]TJ -10.2259 -1.2007 TD [(cell-wa)-10.7(ll)-268.8(integr)-8.2(ity)-269.6(and)-271.5(bios)-7(ynthesis.)-277.9(SLT2)-269.3(act)-8.6(ivates)-276.6(RLM1)-271.3(\(G)-7.4(arcia)-275.7(et)-267.8(al.,)-274.3(2004\),)-273.6(SWI4)-274.3(\(Baetz)-275.5(et)-273.5(al.,)-274.3(2001\),)]TJ 0 -1.195 TD [(and)-254.5(SWI6)-257.2(transcr)-11.1(iption)-257.6(factors.)-261.9(RLM1)-259.9(functions)-256.3(in)-254.7(the)-257.2(maint)-9(enance)-256.4(of)-253.9(cel)-8.6(l)-253.9(integrity.)-261.1(SWI4/SWI)-10.6(6)-251.2(regulat)-10.7(es)]TJ 0 -1.2007 TD [(the)-336.9(expressi)-11.1(on)-331.6(of)-333.6(genes)-344.3(functionin)-8.3(g)-330.8(i)0(n)-334.3(cel)-8.6(l-wall)-339.2(synthesi)-10.1(s)-332(and)-334.1(G1/)-9(S)-330(transi)-9.4(tion)-332.9(of)-339.2(the)-336.9(cell)-336.5(cycle.)]TJ 1.0015 -1.2007 TD [(Transcript)-10.3(ional)-381(ma)15.9(ch)13.8(i)13.5(n)0(e)13.8(r)0(y)-356.3(a)0(n)13.8(d)-370.7(t)13.5(r)0(a)17.5(n)0(s)14.4(p)0(o)21.2(r)0(t)-359.1(p)0(r)13.6(o)0(t)18.5(e)0(i)16.7(n)0(s)-355.5(a)0(r)17.5(e)-372.4(lo)18.5(ca)17.7(te)16.7(d)-370.7(i)0(n)-357.1(T)]TJ 7.4718 0 0 6.641 384.5479 104.2582 Tm (2)Tj 9.9626 0 0 9.9626 388.1763 105.9023 Tm [(,)-370.3(s)0(e)18.3(p)0(e)19.4(r)0(a)17.5(t)0(e)-364.6(f)0(r)17.3(o)0(m)-357.9(o)0(t)18.5(h)0(e)13.8(r)-366.9(tr)16.5(ee)17.7(s.)-360.8(T)10.8(h)0(e)-361.8(c)0(o)19.5(n)0(-)]TJ -28.1625 -1.2007 TD [(ne)19.4(ct)16.7(io)18.5(n)-302.4(b)0(e)19.4(t)0(w)14.5(e)0(e)17.7(n)-296.7(tr)16.5(an)19.4(sc)12.6(ri)22.2(pt)18.5(io)18.5(na)13.8(l)-299.4(m)0(a)15.9(c)0(h)19.4(i)0(n)18.5(e)0(r)17.5(y)-302.4(an)19.4(d)-296.7(c)0(e)12(l)13.5(lu)12.8(l)13.5(a)0(r)-295.5(t)13.5(ra)17.5(ns)14.4(po)21.2(rt)-290.8(pa)13.8(rt)-285.1(is)-295.7(ac)17.7(hi)18.5(ev)19.4(ed)-293.5(by)-291.7(t)13.5(h)0(e)-293.5(i)0(n)18.5(t)0(e)16.7(r)0(a)17.5(c)0(t)16.7(i)13.5(on)-291.7(be)13.8(t)13.5(w)0(e)15.5(e)0(n)]TJ T* [(P)11.4(H)0(O)13.4(4)-365(an)13.8(d)-365(P)0(S)17.1(E)10.8(1.)-359.7(Al)14.5(t)13.5(h)0(o)15.5(u)0(g)21.2(h)-370.7(th)18.5(es)18.3(e)-366.7(t)0(w)14.5(o)-365(pr)19.3(ot)12.8(ei)22.4(ns)-361.2(ar)17.5(e)-366.7(e)0(x)19.4(p)0(e)13.8(r)0(i)16.5(m)12.8(en)13.8(ta)16.7(l)13.5(l)0(y)-362.8(u)0(n)21.2(d)0(e)13.8(t)13.5(ec)17.7(te)16.7(d,)-359.7(th)18.5(e)-366.8(P)0(C)17.3(S)0(F)-358.5(a)0(l)16.7(g)0(o)15.5(r)0(i)22.2(t)0(h)18.5(m)-368.5(lo)18.5(ca)12(t)13.5(e)0(s)]TJ T* [(th)18.5(em)-314.1(i)13.5(n)-319.4(th)18.5(e)-321.2(s)0(a)12.6(m)12.8(e)-321.2(s)0(u)14.4(b)0(t)18.5(r)0(e)17.5(e)0(.)-310.2(D)0(i)20.2(r)0(e)11.8(c)0(t)-307.7(a)0(s)18.3(s)0(o)14.4(c)0(i)16.7(a)0(t)16.7(i)13.5(on)-314.5(of)-310.8(P)11.4(S)0(E)16.5(1)-319.4(to)-311.6(P)11.4(H)0(O)13.4(4)-319.4(is)-312.8(re)17.5(qu)21.2(ir)16.5(ed)-310.6(fo)19.3(r)-321.4(t)0(h)18.5(e)-321.2(im)14.9(po)21.2(rt)-313.6(of)-310.8(P)11.4(H)0(O)13.4(4)-319.4(i)13.5(n)0(t)18.5(o)-325.1(t)13.5(h)0(e)]TJ /F2 1 Tf 0 66.9892 TD [(SIMUL)-9.7(TANE)-9(OUS)-339(RECONST)-12.2(RUCTI)-10.1(ON)-333.3(OF)-340.6(MULTI)-9.5(PLE)-335.9(SIGNA)-9.9(LING)-10248(129)]TJ ET endstream endobj 29 0 obj <> endobj 30 0 obj <>/Font<>/ProcSet[/PDF/Text/ImageC]/ExtGState<>>> endobj 31 0 obj <>stream q 1 i 74.098 695.679 m 504.397 695.679 l 504.397 119.735 l 74.098 119.735 l W n /GS1 gs q 0 575.943 -430.242 0 504.34 119.735 cm /Im2 Do Q Q /GS1 gs BT /F2 1 Tf 0 8.9663 -8.9663 -0 520.3274 70.3559 Tm 0 0 0 rg 0 Tc 0 Tw [(FIG.)-258.9(2.)]TJ /F1 1 Tf 4.0403 0 TD [(Prize-collecting)-262.1(Steiner)-257.2(Forest)-258.8(\(PCSF\))-255.7(of)-254.5(the)-257.9(Yeast)-257.5(Pheromone)-258.1(Response)-260.9(Network.)-261.7(Functional)-257.2(groups)-253.8(annotated)-257.5(by)-258.3(gene)-255.8(ontology)-257.1(\(GO\))-262.8(are)-258.9(tagged)-252.5(with)-262.3(r)]TJ 61.8044 0 TD [(ed)-256.5(boxes.)-257(In)-254.5(this)-260.2(PCSF,)]TJ -65.8447 -1.2267 TD [(the)-333.8(rectangular)-340(nodes)-336.3(are)-334.8(genes,)-335.3(triangular)-333.4(nodes)-336.3(are)-334.8(transcription)-337.1(factors,)-330.9(and)-336.1(the)-333.8(circular)-339.1(nodes)-336.3(are)-334.8(proteins.)-329.4(Terminal)-337.4(nodes)-336.3(are)-334.8(colored)-336.8(red.)]TJ /F2 1 Tf 9.9626 0 0 9.9626 281.8204 34.9228 Tm (130)Tj ET endstream endobj 32 0 obj <>stream Adobed         s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjzm!1AQa"q2#BRbr3$4CS%cs5DT &6E'dtU7()󄔤euFVfvGWgw8HXhx9IYiy*:JZjz ?Drj : V_RI~({~eR;v,X`N;3.tIqkޘ_Ӳ퐿ۅ3ҟk߄9}W'[H֤ ^ ^wXx%_Q)u 'Їߞg ;O)\T?;ǿox%Gp)5@V= zx%3HKoUF׸; n+ЇLՁO_'X/?.P?i:ת̜=[g11S+I?{c/w~>,3GO_J~n#~ }I_RҔ+ѻ]B' =C~]Ek>bOOׂ_KъqҴ2GAW͇0׆/B2vjG/>zWsjR>SU}7!\@F? $ޏ=ZV.LVb _ y݉|?VVh}_Y*q߮GÕ}];WUp}~&=\=T9| _^<[W$?O0WK}XC^ ^f~4J|zw_WNﵷx8u.U\?=#^W^oCъE`J_׷L_j.vy|FC'~pWI)WOAo_WNW5.DP|տE?X?LI}bi}F*zRG8kJ'u=x%|11| _ 6AK/=O^ᯩf_*X8#\RFӽ+Zn$̜a o0 ]D}G>w/.AN)N Z=)=pKߏ/`9#Ϸ|ԁK0_B/8 =a~g t9G?Q?rBij !qk?}?>ޮ:F5OC{oǂ_|?C?_:64s'[V= ?<ww⿙?_OOӣk vP.7ڝqXK5R΋ƓMIԶOыB:~"g<ww8j!_yϪ])z_SѸ5%~QIJRF×w \tULIKz1SҊ>2ZV[0J_N4m]z?W/[ՒNqJRwʾq_+ ( $ޏ=ZV.%+կkEwb_rCս/՚_WiyiJ|zw_WNWUpN/X׫^OG"oCъ+B.d%|W1p׆/;/?UVWƔNr>o"ʫD~>Mz1Sh,Z+| _^<#j?VO^8}o_Y%ҔǠ#ʾ͟~"k\~~~>Tp֕ozJc xb@#28m\_0z}OB__R)9K-)J̿QU6~kBk\wUEk^2z~Ğ=9S1V-ջUየLh;d=kR؎ sKGoUIԁK0_B/8 Zǹ<w(?>ӒWЇ|w_ǂ_|S?C_zU?qk ;Gp)wFƑTrЇ|w_ǂ_|W8ԇIZtm{]1K C5Ǹ7c/w> sK~gEIPߦ[?F/ d?rg<ww8j!_yS:.=/\G}^(d)XWw?`\O.@z*}~dx%b+I'0J _ dW^?|O4^ᯫ$㚔cO/CÕ}_c?W5.@Q{E?Y?LI}b9F*z)>]GAKWϫ_1p׆/<ɱ/ڹ!Byޗ_[x+4~4U>=;rsoq_+\~'{}k/'7ODEʕ^2\}kWgj _ }o}_[+ӿ\*w}~+)r|z~zTZ. *V.d%|W1p׆/;/C'~pWI)WOA׮GÕ}];7\DU[^SĞ%b$|##7S퇂Wͫk`ٗjBOKzE^IYiJVd F<9WW ⑮)r"4}z~ֽbdk=/F*zr+H[w/w> ?3QQ64m v^~=kRH轰pKߏ/`9Ϫ| j@/ٙiVwk#8k?.Q? ~6=`?=?<wwaRR/'H7 zv~XK?3HK~gFƑV"= ?<ww⿙?_OOӣ; bJЇNktqoǂ_|7_΋ƓMIԶ~_bZlx%ŏpxCOoU?кSqxkLa_/w> 5q?Ts+Zbq*Ҵ"za_NѵuWOE}^I9JV$=N<9Wx8 qKcqz}Oz_XoGъG+Itd%|c xbH#̛ '~%WKgJUSӿ\*w6o")r#^WDއ=*V>]{tpJb _ ]w|_-'~%!}oWƔNr>o"ʫ]csCk: %.##UI #LbH_?Flp9#DOkwyV\띊v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*U)}:?[aK:z"KB+7SU_s5㪺H?WS_\lv*UثWb]v*UثWb]v*UثWb]v*UثWbigg=܉$4(dwc, Ey[4tD[(J*4mXv?v,1crD}s̾Ѱ> }cEq7UkzܻNo^gN02G˹_c_r^<>I7 zl!HyD[c DR.^h.tL<0E˹1}k~ޗ#7kxW킣\gqOkh-DK}?:L o؋ru .c,a% J7>&|E G?\G' /"L0arWl>&OS]c x}+#zܢ57}_-BRxzf8%o;Pa˹We7+nWYg*=rSl:M[1OmHJ}"]׶zܻ3 2o5SY?czܻ5qPrjHH҇t{پOm.O|j=rl_y\V??{ܠϘP(KWczܻbԼ#uC)nۭnZ:(lw56y8*7Gl(CW4_?t1ȓEdC=rWt?Wic\|!{낣ޛ=;cVtsVq"hG&׉-MĚL\olqKU0;z+"3¶v*UثWb]v*UثWbPޏD?T)f|O忇U7y\v*UثWbevHy2!jHNedV5ͼw B*ڲtzwEe>4?T'2.݆M619%w}7Tyzip??ߵxa%l^L/+POfA~NJ}~%ϗw7i_HҠ=;[slUݏw_|5y*C^/|:l>l[6?kZzu/s!ϻOm9~dz[xt>&o)}&~\NuU=~?a}xSYG'x|#Q=9(w~+Z '-LS_k?K^$0v?f_os)%,Nz丧|Z~<\'<^-f/L:uڙ,˧VK^$x?{W1}k~O/z\^<>שM5xX8oppʷ>E~$d"?:LJӿo\w|Q\x~Yx_|_VrIxM'R 5xX8op\?{|{(~~Z /b LNK^$x ly'j[dѰ}cA# x}$Jާio 9^J__oM?m<>\:F:</)@='S>_X}/VCcINe}gx+R}CGLAzvW[z5.V:DlSeUz.\o|΃L;?Ejpw?ch=?оMtG{NJ}~%t?:_yziptOx_w~{>/:oI}h ِ?gww_|-7u.Zo49!~8ږ^%|xMJ?}󼗋3zN)oHzplww_ O_\=A9y;/6p>Kt'=7>#y \'l>zXx4x}Bޣr_s7'%n/O[}ad\?Eugxĕqv?~\|!{iop+sFCy՚OKDV.^1\jdxW.[| /xϝ_G<}?Wrx^½7Kw˯`3uW[CU"?Vz_[~0ȏNS#Œtixė_ϝ_G<^?WՄ\^<>I7Kw˯`3 p9CW"O}ko4eR?7s2%o;mult_J}Nt2Fz Hzp+=w>&]Gzr=| 5@*SӶbZԑr%O{`ww_/MJ_}'uo{~td9_Y߄cì>/<-5}rOy4/A].ijHy?ޡ??OM/uow}S')w|%l_yK/+POfA~NJ}~%ϗw7i_HҠj[-xtn=w_|5y*C^/|:d>n[6?kO͏WRG?O5?&gnZG"|L߳|S~L-y*t#y;WdOS f_aXxZ~W/+}FӒ7}__q.^x"ݎ:tUK0v?~\^<>7Kw˫_3v+s[CU"Vi=/?YXzds]\wm4UKk>w|Q\ָ~Y_|_Vzx}Sr\S]~Ư  .\VCyՖOKLZ.^\jdxW!˿o\w|Q\x~Yx_|_WrIxM'S޹.).^ۇqϐC􇛾ExXix/Onjdx\K^$x ly'j[dOS a$ _XxZ~W+}6Dތ koYׇHV`wgoU:<2Fz*Hzp+l=w>&]Gzr=| 5`*SӶbZԑr%O{`ww_/MJ_}|3 W?E?c~|7\O;}"iׄrtB( ݨ+|Nb˙p̳Gm>}4(Vd#JȱcQAڞVXhѢ/? ЬIO<<].<.s>˪D0%%*A1#ڽ ÿ́K.oYe̊.U$/͞? u_=rOyv#BedH&U2);7.Wz'L0G)(q\\C/%,$sZǦ3UثWbXDGo;"=R~;rdJ5}R$Yf;XcɕE*HOݐv*UN,p݊v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]JуO/Uym7Ɵk:onp n5'b]v*UثTF w]Z`ܯڜq?g*/a__w^iZ݊v*UثWb]v*UثWb]v*UثWb]v*Uت[^Kfkd_1P3QZwiю\ȴ:9݇]2.] t|a"t6v +PXd]4B nN <3PҋV8c2IfZR̖M?Z6̨o^RT1Y07O:/Xꋯ2jLE@Vfe/\DDPPROl;v*UB,짺}/O;eDuA*:-G.e>2y?rzS$r=@%ثWbPڧ?ї~>~}'X޼ 8;|* vccHKˀ9ve2FdY;v*UثWb]v*UثWb[n7Fko*S~<݉p\7.u]v*UJU87U:ɞ?{*\ӂ J6ӵ/{d0>+'c\쿋ޚeWb]v*UثWb]v*2bRǸ5MH̱gԴ?:m-Ka zlɘrO]TaK|17Qщ㻎9GzfVB̘9rdW|e$;bQ;ƈI'ʈ=_̸, iIвUִ9*ZpD28wq⣮J<%O;VMt8DkqEN]v*UثWb]v*UتV>(oRꞃVi֫-<\~|U_x~M2 ثWb]]ߵñ<ހ'˺q;A:}skx?47b]v*UثWb]v*9.&,x>tIkk^F2 PR:|V/0nӤҴ l g0Kk'২w#oG^KO1M~cktf/$}>M]SKouO7N?1VYѱvYf,cIJB.ty\?m=NOPӴyKybw! #ǟDV81Wb]v*UثWb]v*UثWb]K?0h]ޟi^GksLm43L*O'e]r?cUثWb]v*h }Hw߳r}R_s_K9\b]v*UثWb]v*UثWb]v*UثWb]v*yj~}Z^~TkT|Yw<Pc>EkÏF><ӈmx#.i4'F3>IzmƆBzzBXfލ6Yg:=xpG`{e6Rw5u;l+!{v5Q |r'3~QyXmc[a!0Bڴa1$Amtõŭ:֏ ._?-L/Ko%$qÝ*bbGE@meq ]nl2zwY1õ l6n53Idڽ>$QEUF;9/vzAxĭ~r_"#*^ЭoO#0ƾE=Jr;'S7#i`9vQ4 82Kii  %ƬKV$%6u^_/8r IDŽN26|<%f52#$w^S/!a׮($nEWb]v*UثWb]v*տﵷF2koJ}NOǛ<_.ˆ{/̹;v*UثU+oy?_,<PWywNS ogu!'?q/zi8n]v*UثWb]S7V_D̂S2×TXoNC>mj  MhȬ#}"rG T#3*1b"?F@:ah<bz.EHV\:fA3rDjm؊r=s({"{V5:…O2Txf&Z]T+GU8Mz4SQeNqu&.d`M|Po< k_)C 4htѠx渝$x׵@e ^hp,y/CmkַqէԡqoQє(q㊻v*UثWb]v*UثTV YVbrӎ|\{WNz޹n˲oO~˒{:b]v*UثTF+w]Zrtg?ܯڀo_k*/a__?NIZ݊v*UثWb]v*UثWb]v*UثWb]v*Uت^B_>I^4n\M=8lrP˒&Ǘԭ/QBxU0i%NkhEf#.^J0-m'44n!^4OAo~Hb>?N:iN82|c@ŲM:e0U +PܙDʉ:^I#^]) t˱b>ܠȾxٵi<噬 `ͥIRz6&:85`lp՞}6ʓBn RJ#J1nG1בOF}wrڎ_޽ޫlȖQ,mBF Iosz'zR#/ zQBgZyo2y|^gCjfvlq^ 4!?4N/xC?'<Ũs{\S(2+U6q9\\+L> .-/2O,4y%Ea|C JWlϘҠFD6I r<ަyA3zYvQcJG/J(RB:po'@,)KWb]5~?oyS(NCy=d"\?ox.vWb]Ryf7V:ɞ?{*>\ӊ+%8\/~k??M2 ثWb]v*Uت]J/4m[HEeą4Ԡ^,ǔu]`Xsgo{ ILҴq[ZV0~g_YiZծ/5K-"=;P{VK's! ( wP淤Yk:v`ڮ{ad\wnJ/]XޒƬx|e ˼ TMWZ~Y·H\&7mc,h>* rnF@dv*UثߘCbuh..o6]O5쒅.U,w[4l[W6bhRSTI)~C2Δ]F j咖9}wEꟙ^][o҉\jw6m&OgjqThwsd1cyZUFȲ?F28v߲''\%[Ղ\ y\fUثWb]v*UثWb]v*U_njzR7(7?v_}1aPYfII-<YMV Ly6C$(N %JzYڝ*|yb]v*UwXZH"Oޑ_MBOU־*0ĂA8UثWbR3}g`=O^HⓏ)~4C7m7Azk_P$r=w4,pv*UثWbR IkZWyC[.R+.w^iZv*UثWb]v*UثWb]v*UB1 1U'y!6Ud1a%FфĎi.]IP\ጎ"W- ˔O̺9)Zs rIR2+@Gw鹟6Oȱ(ˏ8r۾ ?ӢiFr'?Y[)obڗl fkH2Q\%HP>wEi7iYL~|EE8Rxk;@|l$h HI'U9p @ݿ`CDv(d ɉ꫶e"TfIf~ʠkH۶W8Kliwyƛ֒.D$aPv4ZW8ÜiЍŪ\|@?皟9gx>|#nE,?(#sNsdqCLG3=$]2u+ij9*DhPn0d&{0t[i˲Ҵ,g{081зayin%>DLrkCǨq)?[m7Ion5 ~((Dw,-!SӎIChP:ui#+4SnWw7Ar0c|1 H΍pnE橧*W΁MA,'?gEHpO5 Sw1\-_II v*4o8Iɡt>{سm'A th8|<6 ,H'F ˱?`dbq@{PSKWbPFxEkIJI蟰zJ[\yK RMU-0?`um)/>eN]v*UثWb]v*UتH Fѓ=sߧ_UߦSv'wϕlιثWb]WRԢ=?ɞ?{Y<NBH֟nF2cΫ2c2mLjJ,%HXF+T)ZxSp̪*vʚPyG}ee2lȎ!ިy)&xɘv O >40m͌qD9b>beB2G߲wy8^é]^gR."[+, /;VQVmX )9=)s;dUWk~0VV"* ˡ]V](O˰=,\\]HYei~ .: U>]v*6Ock[-݅Y\СT3XdF; W~Q~cJ_N:-F?6---zOGV'}VKh~|5i<]SJ4kEM>Ť\:3NdWN<{X<86qQFVX?"ԗBzo-PVUЗ>1E Vo|B b܇q^2w}蟤xލ-o*I ޛe30GEf?|2(_L5/q ċ)kIgqMrv*UثWb]v*Uتv\bT'ܓg!̩(=&rj7Kېb >ev*UثWb]Srcj[t+-YK~nI.ܨܜU%}SϷmq4C"G<=*a \а~YÁ 䥤϶W.+{6o0>EE{״ 5Y22YZٍ?͞n2ӠpXs鶰7.e,Z6^3?]v*U#C/>fI㯮~.U';ÿxv=x_I?IzwI\띊v*UثWbRM{^s8\<_AiB SS_t|yrN\UثWb]v*UثWb]v*U/&jzq䰴 ]&Ƙ-|k/&?isynXMW n'GS+1pɈ En7 }Ѫ֌Md|fy$̝ { Pizl;j2f~)R]@޷[C =?*4zk'[Ö(s ecVӗzLG$.Ai3鳻D"D Jn!$R(FXCy54{˩9Cs KvJB8-|vxt4_.gpQc4BCvNr6HٔE"a/n0= xȐ3O%9Kɯ/ vbܞܓg!̩(=&rޭ/n@>Cu{og+?HO@ u\ғEć@_O߽e-ͧ+}-Mjbv>*IB{WQ청JfScˌF'_7wt77 M+T`(cL,fH7kow bkT))rZEls[ 97c"(Vcy.^MU#HCRz2'fAyWB.meey7~EԢdX&Wb^U ݾ0mAi$|eR6whX*ATwO(H( `149 :Y9U]F5~8čNnGQWVg`LvaveX_M] z֟FU *0K`ݟ钏0rS㉧Yt[|##,v*UثWb]v*UثTz_G#o'?қe_lKiܫ%@Z2?Muk/iJԦy~}&{ -~; X\?Zlr#jp6@!"OE >ᑔ̹Jv*ysq/eM3Wb]v*ohdU'r#}]_r Ch1*ēܵ^mؓ֕6N9_N1(Aj`(TثWbK'K)2-~W-yǔ(!öIKqi  _-܏#/xwj/5?Pq2zg kEX_Z[܏e1lx0R#/]uz)Մ~'_zښyGN ci)Z44fXr`M m{CeAx۵A" I@+㔥 b<ݥ15^L"sv$+QAQyB[ev- 2ĢZ7j⨝+^T+/K/u>_ZdX7Im*b]ۮ*WmhzK(O3'ǚqlv*UثWb$S|qO4Q]FڈXn-lnc *0_nCGc}#b]:Mk%11Pc@>!#0tZ9-+;-,.%ߓD3;*Ւ`gYm|(QA܅Sc S9[Rkv*UتS_X=~~4==U$x/V -ߩ\2d9q6\b]v*UثTIL<ޟ[Q_a^}Rk UԹHu6\b]v*UثWb]v*UثWb7v4r$P%ȡoN3QT ~^yMO.v2[^O%2E7HGdxx)wS% .ifO,ivasyvPxs@.=l洚7dkn Fc tcN&ղ*UثWbR4z?O}}d_POϑE?GZя^)Ǘ¹sHbR۝zKs 4DhԨjV <&/&yZܚŖio%SW7 LhB/^@&2A LFhWQt:̘|>Ǫm̘ckmYtr mu^uA}%>q}Ӿ[/m3ʒUثWb]Skkv HA* u?N*KI.湎_HDPd'kB96G)4;kXy,Έ( O62"Fݸ*}bBʽuۮJ<%OA&MբMu|##,v*UثWb]v*UثTli8ovx>~,û`okvO9 \݊v*Uت~-+^ N 1Ng_I1<)m-ip$d1}#}x#FC#YcUثU:I$jn SI=1TQ7"X+A"B' -b.ҤGv#<ľaѾ.d|2ɘd١IZ5i# Z4]v*-EuVOcb9ثWb]J,ܖ{;2'Ie̼Ks?KMWb]v*UثWjz.h:hZ4ZM-m;?S[ ƽFXoM{gԼ1hvYZA4 q1v$rHMiWi?`gkHoח2=]e2+MmlaEPገ6?>3Bj:,ZޝwgMњffi DI6U~_&t[=JkV1)y#7OBToUb0*av*Ul m,4gc@8 է)0a%ٝNaXb7P(GqFơ#QEE $e UثWb]I<_XBS6۽WZ~?߲w9N:[v\"~y'ysv*UثWb]HOCM$Zzѷ nwq|UR^weιثWb]v*UثWb]v*=4ȱD rQ,[OPt}8\Oٟh3'?;4~э%kM)5J5 FBzGǸ~􀆹зoQX~G?H_4sN4TE Ulc2Gwvn@JJ3f&byNX2dutWSU` "ffk6O]-+ ,O E(B+Md?ޝ9=~q@G ev*UثT=o[ГA?.&l92䈲+~|iԧ:LG%l v*ijc!n,ע/, s_ZaմJI٭NO 7\v nF"my+͓ʯ/fG-Z3\C;alAִ?PuV|Ux(,z֛a2?y|-iLUgie| w'nemiM )GoLF5d׶mLgs&'dPw'?keM@$صK?jjSEƒU䲐UHPԁÔ 2l)gϐkj鷖SEnn${ }3 H-х:eWb]v*UثWb]V)ZSbcH钏0rY4[k_^Pv#h( Ȳv*UثWb]v*UثWbR_Z¯o_Xǧƿ+O?7\b]v*yOOʜ}6"Uia%ɞ/{)z?3}/J~IJ|nW_i_'w|G'e Wb]v*UثViks\0_F]:=[R~(FG\U~n^b WO$k3 ehvTM_QRjEͫjڬkwiڙoƪ$dHQ?>[S[tN^ETO2*<3^_״řl/C5#hd*WއǸS|UتCi%yz[[)2 쿴J?my'P!4nV.J ~? rpxig;]O2Yj a1 +ۧ/21"WΛ?-|-jVzf'ԯIP,4.է0H۾c2$qH?Plx+-AW]v*UثWb]E^@HK;)(+a^˂&ҡ-';ҧ-c@;&yJ\EAo.+47S^W:7D;*eWb]v*UثWb][$ƍ$UrpIY.o M"U:٪jO;{W y_nokZPh⸇¿=ϾFZ\01)1jS\bt?<>'0;{t; ǜ̉'dER5Z,*,lT +1@-dK 1#5B&9H_V)c2Re #P7EHK}=SK랣`?D1Kyp?'}w+K}[iZ0{)O2b H$FVbR4zO?U»ǁ~.<Pc>EOMt!gk _Z8("H '\e _$ _7}/WE??U)N"z*{|9w'w?ORXxz_Ry̔ڍwa`=;|ß+n!7r`n$m˹xz7[ 2-yZνz>߇|^!ށֵUѯ4Cn/ !q+ng7l<^1{$e/43G P"TV[); {&/N<bsW-cmۙL*[ xIŚn-~^fAY2|Zz?) GVp=PaF6;f7.w+-_ORf s%xR()%!ɔr*6^SoV8ZKd'~mBge__"g^q%+wQd8s '~).9҅9$~?DZ˹xz~%//ZD:W2|@x`=\}v>}M~>w}oCzްETS^ (}qy~ky5˹xz>5//]Sh_⧆ܼAKOG'k)qzё4,>8|9w/U=נ}Y-?Qyz'$tD0p o.^;oKҊ~~SҝDwT8|9w/_C=/)_ð{w{JہHe8\Ie=aܼcGRiln.X"&Kt>sS F `o "t?F%"[v1,OKMId"~|{ɇAIy[򶛦g'RM^׵qh8О3uf)UkBҠ-'8=8qFX5T`Wb]v*UثWb]ZW>XQg>NYP1Y;Cj:66ycPD*(9n,Fr&4 2^^ڍ=b7TQbOW;}j5! (*ݘ_v*Uثe>\:W~bȣS$Wӣ(=k8xc@XV].a埩;$DݮPTOA(U@|O?آ,|fGofij[I4/-dR4 RCy3EO0[4rhC$l!@hjSDҴ=.JmO^[^*+S֤MI;qWb]v*UثTſx]߳׶U;2])p :N^UثWb]v*Vy[4gQ|qKxoU`W5\]v*UثWb]v*BIzSJ[{1i0q\JPp˧ō7:ͪoemWX~k4Abv*jwP935d+HOwA( ,mj@%՝vv=؜.S9YP)تWc2[+/kY?ߡ2P'^3!}x/T1Y;v*o[?21'܂b%mxżxt6c KN$/.}bv*UC<^.|N\qf:N(fLJ!S-)NvLjPr˂ה:V_t<~"Zq1ӢZ ~j^ ]=?oq+A})XiDݯHZ,_ ׎ (➚yOxo}._VQk1D=:>fǏaӏ!Nw>8<}Z.\pZA`{ceh-HxqhkNy2ҝFW1'. ^j8Vh.eh-Hxp1Ҝ r+J}"}Fǟ?ϟ˂ ǝi_ l>M)×.*}57US?K-pv*UتOˏM̐z0K<_PQ?gGU SoM| oN_i~f|\W~ m~-p]v*UثWb]I]OQL =1b~C2 fg'rFHMSX)Pāf+$n*UثWb7V71#aGBnIzgOךxRY>)ɜ=Y"6( b]v*UثWb]v*j֟w'g)XsHs++%M8H`ܜbdhsTN[)T>ݶ(?3',#=t1;JF#ױǬlױY5C7uۉ+\U ZGj)pX*|J6S*u#-uiiuoyżۖ(&8)q-Vc904+:Ha{+E'Dc ױNXB&i;SQZa/S9L8^5/bvy|8_M[Z&}1ٕ^ V0c$nF |v*UثWb]v*UتOIR9WbY{YNf{lOO<ӌv*UثWb]J=_>>i^O~>6|GpX]+]\v*UثWb]c/_ivZťkϝRv>Ҽ{y˫k0[[h$r|kRd;U1`*żק[yZP:2) RJ>FVZ\*4[_u]N+Ļ9C2xz3{fHp|{"DDPQE@ &o@ꚋ[[h{m:fQ7'3]Ly7wtQ`͗Dr3)KWb\?nB2H?eKc=U5i'dhEnm[H >S#;eisլW12+ɅrF'BA][,QKE* #qFF<8c" j}GP~-4bum2,a_~5\a+4{Mo *S)ˆP˿H6ʒUثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*hiE??2e_??Sgq]v*UN˗ ;WjLCނ 诩gMEax|">4xj~{v*UثWb]v*oc@XF>Yʣݎf,fr&t{)-m+9 ypk~{(G'%-(.]v*UثWb]v*UثWb]v*U.69~ OL dK&P9 @U 0A<$)wvtW.&CƇ?,?b?Yiav*sej+sq# N/xG5o1y˱NAԢF1 B;vAhNc%>^o-MB?)˨Xwi Ÿ r8g!PƙX~JOPۭ /,Cش d;d<}9*GӖ/#&bowcur H٣??s]v*UثWbo=/z}O÷]u._j 7U*k}OrZUثWb]SsH ꥅ*>XĴ ?̺*~W[[ɯ4I괰I KdZjd 1WI$ -BmϷv~I ZZeȸ++Z\z &z7,d2,|ϫ^]Եۋ(fM>P8&-Ў TLym\UZLaxƅiWA8a[eAkWdWG]:˲#hŔ)v*UتXv2deVd?13$DGM; YK?♪KfV#? MsWb][²7(#Db(m=ǒB JO"=YCA5#}-c||]sM:ª|bL]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UتL X|Gy?ҟoÿ~`oS}?{Nr^UثWbT8R~\xm^uN'Sz|Kf/{(z}3tzi-5+rO3#Wƶro.]v*Uت$8I$h ;7$b5oL 1s_SWBlo n$LHh ]v*UثWb]v*UثTͤ %kAoݣ!_gUo8?9\b]v*UثTK_ϣCz# =! ߦ\/w9 p{{k8N]v*UثMܓ-]_H5 b_Lm7/e1?}n"4k2S]Kԧ^U9ܢ:I.O[C$vC6"GHIEe1ԓu 1C AEEBW:/MG~YD!Ԯn7KcQ }UO!W󞱥^]Kҵq|d'z`F)^+gUPT>gs‹wrK;&@ٕ3Q^jZz|2EHGfǧv*M^v*U,|du30_T1%Z.e|6j(Nebc{Cs5VN]v*U"ARnlͣII_AxSxolc]Iquj-[xcHwFQ O']FzYG{'"U.V[[Kq eJ'2܎d|?058|c4hldm%Rݛn*~}e:ShtUOQ~axh _-_;^?{-'}lkF><`QݭR*;Z|n#/ ՞n,i?CL|?0~̰_R_W~5NjXHdS>lGOʖ锧XȪ^׆ߟߍgl'laxOm?QY9="ߌ~%^/WANYן߇)"D`|,m'.?Gj<~^de>=}B~ x( ?Z9}gꞧ߇/K9tls Cڏ Os^~.x(?Y9}e=OQzd|!O޿FWdId|ߊ~&^wqoX~{_^knW~?P/ۍiƢqaO?o>^?"y(W2CƷKZI잸^?"">+y]r/TIglaIslZx<'bR$V_Or~U_~'ʿMثWb]yrNUjLz ˾;z֌m?*owǎW-]Ko{׽1ɸ]v*Uث޲[G*tHFH?iABY=A-tf%sm$L8Hm҅jVe o e5,sDMCed7vTO/)럔m򶋨i:lwMsgmko\I=xoHK\N*oVKK%;4m|%qWxWb]v*UثWb]v*UثWbR:yPyN7&ꚅ Y:o+`cqX54;=cG_Ee}0I >#*vZ֮un-XESn `MbKɌdˠE6k:ߑzuɈndhSURI_@{q2x/XYrT⬣v*UتWmiM V/oM3V7tkx:H~-bH"~sJ49~cTEeIv*UثWb^mmvm="lk=68b3I;Mgt8rd =aĴNԯnI[(dIT"nn(~v~6QwW+y& QVtJR9nHǧlY1w~[yVܺ{ij/gk )cU pgYkǷ1Vav*UثWb]v*UثWb]uE+@-/gn&aBM1UKky͵F慕kFģV*]v*UثWb]?RھkCt]r,%'y[7bRQxoo??8Wֻe?>^'E}?:˝{Wb]RIqyVOz|K<_PP?gGUdH)M5|9oN_i~f|\W~2MثWb]v*77@(xXTy= Q oRs$.ǔOެzf>I)ZQ-d4 5?T91Wb]v*UثWb]v*UثWb]v*umL !"~Ԓ6ʋN[b 'O%]Pp}N,o=!_AWwep#pX?'c]\v*UTo.׭4ѳ R[L?"V"D^8qV)iyEƖ]oXϣ)/$6dS{bʚOtf-H$ҿ} щ-PL`)S*Ŵ??lӯ{rA2Z<(Vc8Vopr唀DS.M3TMEo!MNefc?_gsMsWb]v*.|y){K?XQ (yYbbU*V,}j?ɝ+GK%_M$l%(UR9MK8CKit8qv-ͧ!& 0@{2FPu\zy#K~CSHlO:Ȟk%U$hͼj(Hܟ:q-// A;3Wb]v*UثWb]v*UثͿ:Մ@JG?qzy]Wy @F|7Sh@&U2sʘbhF \P ҝ;a+7?]1VS XG,g֡죷5Ǣީ3\3^MES*b6 Σa{ zdy56wm$]xJzSAR՚I$ ?3cyo>c611"(1g3#ddWb]v*UثWb]v*UثWb]v*UdE/4(gv7$#Czt Z i6̜ FثWb]v*UثWb]v*UثWb]v*U(O,z"RX.ޞO)տdo*s:M9=Gגo.]v*UثWbz _AiH dA)\Rv:/ UJ>x3y:bX|_LK$R>7V t!)<~SgjP\ -:iInٽGF1##ceuZ jʖSJn$;E7b0dC} ZQ:O䧓-/%Y\[1Khܫ޸/t-/A4}.BpER ԒIfbI$8?[,8CpY@yv2=Z%sVo,$1UتYW\_vG̝>g?y Jg̝v*UتWk-_VX1Y;Jy!Ҝ3 n'2(w,Ozkv*UثT:n|? 8q<$;N}=#63v*Ӣ:u (EA*Tt"dVQٕ{d!7cU'2K2j[IմcCW(I-e? cOLƘ6!5y!awLaoD&~lцGCIaqGBzToױediH4QXUثWb]v*UثWbKNTJK&9JT~n,2.] B-MPVSN?T|?<=wE_5qM"M~$kШ=EY^Hg ~"fV(GcNoc!ȏGiKtɺ<ӇiHB~O&w#/ ?E%ߚ֜o"%ՐfX:WNJ_L߬-='V^A+]\EOmo|ƙ&6~xek)I4T4~$K"p;Ȫ{.}ktqWazqPȰ"eثWbR=|_A=f/Z~^u|35?er,%'[7bREٿ=sӯ)|]p7wʷN\UثWbT8R~\xm^@Ӊ`&xKtC> )Oٷ+DHHlv*Uث볹?Ϋi_i=嬖/mDj'y?ƷD& 5֣ogwc[wHÒ'c]ڸkrѿ.<?̏Pcy{,QrOP*ASt}ci/w{5m̷-^QWb]v*UثWb]v*UثWb]v*UثTu- 1~c/#40;v*UثWb]v*UثWb]v*UثWb]I<~__owJOGr^v9Nz'c|^/eH'ONi\띊v*UثWbR'3?VKԝ%P B;S^:7Q ]O)|9rMثWbMd;4GNe1~MWbP-Q ~KrE!!4Tʧ+) v*U,-?\H~ N/'g̝v*UتY-wlUG̝/Ge1g̝Zui5bddo dBCbވkdo50Gq(%ثWb]X?ܷa?F'{ᯩv^fNNn]I/".A%C#[Fz4 EZm7WǕl40iq$qDn``dO%l*еJO%kZޣ?nuWPH5ޒ4+:`ᗂzw9Qz'_|omq.RnXK"ZhI'#2^4RƂD3_kNjڷ,_:Ǖ.)Uԯ-KƒV4FHےh{nUL_#\.:N?oECj?ky+.'MQh׎T('kܣ=m{nE*}[^P<>\cգd3#Ѽzbڵi~մM2dRo]7W2|GT&WT쭧}a/|;|6[^R;v'p\ثWbNZ?Xo[ц9c7K_MLyl7bRKV?T)?f|O忇Uw}<>|5'b]v*s_KJ׃S kNv=-z,=oT?^d$? /kuUy{,v*UتUn4ۘ5HN6KhQ؂2QR=Z^aZx!RC4#H]OOw@u4K*wY#{hե;a}GtV~R͝im[EoLcZ[xXmǎ*b]v*UثWb]v*UثWb]v*U.jE( }8MӥNn5 ao / D#K{MxRPGjz: Ɣev*UثWb]v*UثWb]v*UثWb]J|уǩĔV}|-og#{SmN]v*UثWb&!=ps v iЯe8~ŻU@Ϛw:bRjhK[SK`?QWxxs(%gk VЊEQ;|$dyWbPi%V/1^wTC + qt39..&RF8mG/DW)+iD8TAQ`zvh6VqԸu5h*BLU%0|ka=^+uէ"/"EecfXOcUM:Ԏոċc1J矟>^;{[˳CsUj̣O0c_v77Z-jp\Zi~b3]*._𶕏_hcG}y'9ثWb>_@~}m^Y#>CJd9ܭWb[n?Fr}kcNt~<݉pÆ{/.TeιثWb]]Vڼz.L}CޗO iG' -m)0$x~Wi_'w|GCcMr تP@v>ʵ8@'DIO3i?X-Q.R(B0ͬLwHcc!-XPGIes"RG ~yZ9ثWb]v*UثWb]v*UثWb]v*?֜_.o!dM5*U1U86?0-럤o[ў K6O R"ui-^ˡY_|Hnjq!մ@'W'WhHyn̚.]sVtQ^YetWUb]5 c8m;bK'Y#oAF*v*UثWb]v*UثWb]v*UثTV XoY!~(.U#;ýsݏex+?Iv<˝sWb]v*UتQ?Mk\r%=^*~ʡK)׃Ӓo,26)G coZ1IXvo_~d["Ԛ?20] RN W%9s@0h[L:̲sq=k/OHzMK!V.8a`yZf+B2R=S]#i־U:[i=JHcW Y$?NUhT)viki-.RRT{sY~Ԑo9-D8rHyH j (XT~Ġubjiw'C;\ZZa˄qO#ꠣrv*UثWbTmaӔTX:2rÄ?8#]T7C"8cXPWb]JBfx ?/*^@ɏT1Y;v*UlG,m7]Tv TY4ˤ.Xi jvs>=ed$x~moJ~=Xo_GjzOR oZvƨ0;v*ԅ6꾧z}ZWZqUm5'b]v*u_KJ׃RLCހs?_NFYOڝ~CC?ruΫ&L"R)UثWb]v*UثWb]v*UثWb]c>Eд*,DFXS0&GE~[a򩼇ge5gηVHI绎 iY[гvc+^4F$VK˽7K[oX5Ko$K*]Qڀ|=MJ/V ֊VYQݻ"0 8Ba?TOe2//%XE5}m.Gj)q=%K?9<Ǖ >i%Mjc`35ze<,,ֵ[BdZIrvc.$2Bzeœ N}KϗaX4pMvr4q'5Rwe7Vc{/o=kjz!m@YhaATs>v2]v*UثWb]v*UثWb]Jу$RK^_ }yn=\5/9Ϛk8N^a]Fj:6eH0IwO4)a+Βm;KmoB' TFN1Wb]0OӺr2ȭ_9a~U_nU~/tӬ׼_lë_=vZޡ= Y0+itRgΗz:]EFK0̎uѣ߈2b8*"`A >+_7]Z]WrIiP!ĴFKK)1n4l|w%ռw4YΣсRȒ|O*7@:m+Wb\@ *U(-3[ʾX˦X264uoe,\I\v>IdO4N;Y=73'taPF*h3Ei\<#r~$i5̋ +ע #:g?L:m =KRZYҤp"fh&Ih:lrY% 9^U榇 ߤ5e,QfҡA~*EǂU;e0NXdGF|Ŧyf[j:Mc29 o Ӗ'd^Ѽ5iVWf_Om$VҔތ)镵"<__}m\$=}^yJ!tXKOrn]koZ+ֽ?\uzUe_loO_e'sv*UثWbWtե87U:ɞ?{B.ix-͢nw^ ?@ϱq/zk8H=&mbYTH-nUR m'OV;Oum³^[|Tf9Y8JLZpiZp4aK 'ywQ6<2y\ ;1$eT(Oqb3LqWb]v*UثWb]v*UثWb]v*UثT̟y+G̭'G|e1iv*#zޮ2ƷCJݤt6.Sw4MoosjZZvD+^(XJU&2spo-~BJCKC`V7 W#J7/ ANSfZ#е jL.]n^G/ \Dqujag i㟙 Q^Eru]e#u+H]J(z%07X'Q`rIfW#jTa)9DFŕAẺgnӤq-*9k/T~T%Ο^. h U"}yEבX$n!5B9G)av*U {ZYEĂ(>ⴉ]v*UثWbR/:}W*gޟ֭*N;r^e9z9.**UثWb>On +t'܎ǿ}Rs?K88\qa][,O:X#Z_~( 4FYszGu2k+#:i@-?qF}wh[_ y )jX>0Hn?[`rj]o}}t2}QiL_("ިl<~r>ȴJt߶ rX44p|ZU_Sl{rԻ?̵$je(FkrԻwz_O'{ޭ0cD~ ־GXr$oܚ=n<$pGEK_>`?҉ֿWqhyr||t rM?6}W鸾cE=^BnMǟFۭpF}w>($˪Iǹ4{WWK&ci"2}Qi,y?/1"@V&2mha}:Q xB.]btj8FI Tވo?}t>czIN}&O/*rj]zŮeO l# rLHo;vWpS̭U''#~j1mC/fP#kbv*UثTVrտqXy}N0_,}V'wcP[gJ!& !i%yOZh\2H]H]Zea\iwUƪo KA>5\Ymp A;2;JkZӃ~1V],G41Y;Cju"9 Rݎ[)"ЖŵXjdzϵod^puPz*M QP@sDb$)Yau6WR#،_v*UثWb]`?켛nvu_{Z7*:ծL\Ѵ-^ٚݖ9VX#'[ v3Cy5˵c5[B B vTGuu ,$(NJ{\|6cz?<,^Ҏw7WK9TtcHQp(dXa^qfF,Ihڮmsa5dH&(D)&cߑ4T5/tK\Ҧ{5M4)p D Ez14meFև{*o-FkȴLk,f+$E?FӠ22X֒xeM\)雩-~ j۝+!ɫQ h-ռ;R-3N{5[LܺrtIŸ we34>GH~a^IS^7;dTX˘Mr J [B_U=S?iח[xeWb]RyfQkc_y3rOjOOh!'?ri8n]ZDȮHUv*U/: _B0tXXƧ*0z_CqePIU7^@mTFq&} v@sNq:2qWb]v*UثWb]v*UثTNxGTNc 3'F{{rL(aЀGӘ2ov*UثWbP:\hZ ^if$Y6 7'x&]K-SKnHtMhQbUU`=Fl6- ?)RUEMtY>5h%33 vk0^kUΌ-`g1FLuH$e-h8$ZIA3h>N:uħKd5 "0C%܏/@ v!%Y<ĿgP׷?'LJ7Ep:i*8|]'h=;CJ*)QTmֻ2Jo̙ZʶJktF2q)KisN wCϒMΗ=YJX#7L"' 6[7o4[̚F8m|uM.Cs ;#sl#㍩U-ăC(4Y_|kzߕK&KOEB-JzAcM1zn*UثWb]^eoW}Wk9\2}|\v*U>rM KՔ϶z]CWtmOkeq4͝>%h"֧] o6 EHr-A"CM*b݀CAw&eioՔ,+rl+2㑗zNxTQ,ɀ@i)Jt@Jԛta'C4G,%'9[4^I4[V[?ֈ!QF@N)l~(2x-3XP}Te3 JE]v*_Yr>ٽ/_<}/K/{Ǫ OKm2-o< !db>`Z͞޽;1,o~<<# WeJ ɾeVo>m`U6J8x ;D~4̃{Re_[NN ok&&:?{>qP-\|\wjg,h=A 2 Ty\KZ&W6eG|$6@c4VNX/湼a,k]OϪjW*BE U,Vb*őJ˖Z<aKr`24iA^T%NY-Q}󏛠,Z~e]G̲xux(TDk% 2dٖy_.,uK%ZkhRBa&eYѨys2g׭ HV̼"khIvܨvkv*UثWb]YY"GwwʡFV*kE&yC<4ʓ*gF*>ceH OM[; =-mknAĀQPLڀn9)ӹZƿSvP%J1RWcLD]Cϧ\8{hqѝF*T` UU"LyާV  :ڕB谗0l݊Hgy4W<=sӯe;x><_.pwʓ̹;v*UثU+oy?_,<PW)O&Wogu!'?q/zi8n]cg[14_ʍQIݵ/2jVlԐ!dcj2_ohVo/O:Thu[Pdb (1Vc??/*ui'o8r(W$1Tʿ.]j>_35[ZI]١!qV'W? 'VSw|UL֋uItWIL!3[әJ[U']gz-as_i,GI'j*oƻmy'%XiZ嶳kWWKa*+=6;b^V4^kz]V\\,^mV"/f1TV "UukO[ݞkdL:6bJZ_aO6k 4Ut8;<R5tum9-,-ݩhⵍ yV㊪^q.XmziH, ;|UK?& Nuo1zzֿY[P⪲d^DoT⩆/㛨G h%.0C!B\S[r?ȶI,vZϘ]66~ˋlJ\UvZ>gP4 UUk\U2S _?0ϧ k㊳_5y[loXU,D#hU 銱+jz֟Xj7^ѤP,0J$xXϛoXksjqGۦlpWӸ C4o*]^?WJ}rDK=]6_6s Q%ثWb]v*Uت-$D@s2& *!1SAw$ԜUSv*UتEy[Jžo%ֽũU=*(qos&ilVRRUi b= eA[]J[=D% xeܢ|*bAU9D 9%S$ǐc9nAJ׈5'#'ثWb]v*yߡW?V1jYZ.^q~j)\;1vW}5Iv=˝kWb^ 94\j~Gҵuk7}&K ypnW~Sд=C@4,;ck) bnڸ2]Ibuitg?ܯX_k*/a__?NIZ7^T nǧ|,2rN2n]v*UثWb]v*UثWb^Wef"[byVIc.4CeAM {g,̼xN(۵A'~ +l'[s;O'0J/}kM?)S/RFej}U?lX1Y;v*U$տܿo\zVY/W/|2̝=!ޝlrȡpUхA wIm̭,\I+! xu{̬€?/fsd0A + (#P][sw2[D9K4|Y*̾\-BMV,. k.|B[c׺ͽot&ٌ_REu)ˑtEFSC!#ȤtH-{v*ZN=YnMfyeiF OMk&SkA"ʞR5y˞h{iu8K0m{i<%K#p%&KJQZeTEs'9GkJ5MPh#^[%khf[̉$\2xt+u}@o}|\v*UثWb]IaZ`_Gؘoq?g*/?S^.\W]cӌJ<7!t z@?'v*UثWb]v*UثWb]Q{ Nܓ}d~\uv*w#?@әXX?Oɉf+'b]z܏oK/K1*;=SL% keqrzC?''R(*:-m!ov|Y P6F)`:Er|Ɠ^zD(%{TGPD'JVI=>X[=P厇/.t9,$o%+ۗ|UcS5-2 wVO+G MiowFY)δSoʖ[Λ国{_0[\7noIldGت"O.7]q<ɬ%j7ۘd{ò[GD{&*UثWb]v*UثWb]v*UثWb]v*yߥWI9z_A՟jm,"\{v*U$_CjX7d\jv>݉p?Oyߟ*;˝sWb]SզkEz/|LCހq<8`ނTIn-u#HЯu\쿋ޙWb[ |ңa~v[so/% :nXj?wYya4E}*{RfATb?:r:.mks Zc@'/YkZզyY -oe#EmjXZmS;o>̛>-OM1_D":0i˗㊵˽;@󏙼ou4^gx q}] N޸տ#!3X:lAoETCLU7ߑugQ%R%ke*d~6yYcU^)]FwWq^(I"^~#犱on|//3đd"yg*S)t?sf ѥ28u4銲IF"i!ӭG&X#jPTQث/ך/u8453i̤0-ǟMxװ*yoN|o5Au4^fkvp_VBr޻@y^bF^ywPv>zIUep $<+isΡA<wwn=`Tƻ" O4>V]Jڵ6Rڰ_I4e r:Uڟ~awdѭgBNʣqTVnoiZn,\鱼S*4ęI v vX痔O(7j_b0bcy;3Fى8=6/5k6^Q| `]G "DͿ V˫+Ti#uA ㊰S8quay]Լ:4FH,GAA*̼s3%Y&X/()1VEYGcYFţ!FnFA4*x/ѡSWu &OF~5,ZxUU坴K<ٕ1$1Y;v*UثWb]v*UثWb]v*UثWb]v*WmE$ӏʿdsSwDz_O ;WxeιثWb]v*U$}/K>-3Zz4)K)jw_C/\פq1.zJ_Z:|Kzw1}L2rNrn]v*UثWb]v*UثWbe8i$`,ƀ' &tʕOaB'aYt1;v*^nެC'Jb*ZirH={ y3vLv*UثWb]v*UثWb]v*UثWb]Ju_>ޯ/B^W']dOS4{(w\IθCH}T$^Zz> /E^iw?:S O~90W;~o8zT[ރVSu잵Y;O:=:}J\9ܐ=>Tovxs>hwlqNJҏ {xYx_ӧw6mSK:S_'ݟژ_؎=/g??{-Q[JVֿ~Otǥl:m|܀}6?Av5>'?!N[ԩKbG҅yv{xXԿs?OpH\ރYlQ6qG0VN24ή?9W2yw*_~i7Ez ZN: O~9W;w}?VOYzГ }f^z~&qMz.d=rݯ_t+tja0ǧez˟^CY_}eQRؗr)2U;9\z~\\=|WN~e~$OS 둬r[#C魇.w׹_?+_bV /WY7f6 |z~\\#s˕r?VOYz+Г$OS4{(wdaq})k9sM}bE姣NB/dןGqҘj}ɇG;tG.5/yҧ׬_Jr[?=kwur!ʽ=9ϿP$^Zz|HeE]:\mA>ӒH?^Ƨ:~^&:t.&Ϳ*i{gJSѿOu?1z_ӯy[tpg{xWK:t.% /lqNlOSxio?_^-TZz~#zjBvgqK?DY ?UNegzSdc/KLCzs'wW떞_K?íp=5}3w}J?VOYzГdOS,{0wda'\Q!רrO#!!ZR;u]M*[TEn2r1$tg}Wʹ_9[쾱g^WLG[]Ւ][M'>!C.w׹_/y}nYV?zTdΜ]Rڙ*ƾ=?.._>\ztgy^NZkϏ_Oxֵ޹\.&\sy˕tP_X/?"J-J9wul4_Dx^CX~X'cI^mdݛژjw5~qp.Uw}[^>e/BN>==O죱|INCHgV6h;_Ku?0=5}3wȎ]_VOY==Uzܵ=O=kwur!ʽ=9ϿP$^Zz~zl袼xk0_ǏM_LC=kl A5>4ӧw.6l+uO?Fy?onƧ:q?!NoʊҶ_ݟ\j}^=/g_?6ni{gˍzrc~Hژ_؟KL:woRlH^P>ݟ\j}cǦwR!:t.%VG׬_J5m&?h :^&*tO.5O떞nJ/Tןw쎵Slx_9ߧ 9)}[^>e//BN>IXXa \?INCP̞GV!C.w׹_7y}nYV?ztd?e7JmLNcWx.Uӽ_:}W~n<'zԯ|˕tP_X/?"J-J9}&!×;ܯynXz/:DMٻ|_>\zռS^ $%fzzaWާdaq}#CHgV6h;_Ku?0=5}3wȎ];W֫o}>rm y)~)|2(NX1ˊ$~RI7xdY{v*UثWb]HOCO$WZzѷ@Fru'c0T;'sI|.GҬ\;ESkJu;e9'Y[7b]v*UثWb]v*R[S1rXWb]v*UثWb]v*UثWb]v*UتQI ~r-=&6u/Cl9|7bRd? }ck[rwK?S|v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWbR̗Os*{Ꮤc4VN]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*_X1zCGT}WveP"8|,utn' vU6\$Xq_լ|~s׌rn7|\'b]v*UثWbTnm-TV>[(=X1UePnY}IXuo/+[˗D.tC5ga\d'ߗqcy|~HܦvVpmbXBĞɒS7#iX`C Pt42&a+Ei7\F\%̋KݒψD~r_%ثTW@>Vdfr~s:oG,%+fUتwsZ&FB|*:.nثWb]v*UثWb]v*UثWb]v*U$ׄt.B2skbUzd9Wb0 1cEߧ9SJ;?}NrثWb]v*UثWb]]]@LCI*QV$ 2r)LOr\G~e/r9@z7_=,|O#?W˯r/?S/?U)۷ 1{`c~C=yxNO'}~SԊ՝yĔtw|Hj UˤMb&~).9҅9$~?DZü2{ ]"T;ޏנ}TEHGJO >${O5_t˞NZS鴕Ň; \y׾V9zއנam)_⧆,{s_d/7N0D5 zN[:cǶ>,{_fd/^z^_mRm'=zD~߇|,{/s2_ze ~e/r9@z7_|H ?%]O#?W˯r/?SYyONݸHf=x !W`ryzߤ/JI҅9$~?DZü2{ ]"T;ޏנ}TEHGJO >${O5_tPbW\j6T}>IZU8Tjӈf+_c꿇$'8W|*xf?VkU\\ײ˞N~zv?+G]{u_Ӛ7}z[koO^^ҿl'O >$y[_2ʫK^_.>;_GKSN>餕gAü3O]pJN辯=_VKO^^II+>"; >${O5_КNOKK%mqJzS?. %vG# #ozZd~k?W*yR'ywyJہHe 8\7[Ie=x%̎G~^ L}D+aYׯXGs?޴y@ PXU:]@zcǶ=y/s2_sO;c?G7%=}?wyB$[ԘuuvǏl|X俒C?W^1yFۈYSHŏxk̗?޻\'0ם |{a#(j yGK׹gޟJ,Tnfzפm}M~,9g#̋}nsFAzSҿoO >$y[_2  e?=_g+_ᯎ6'/W|<:ߧ4o[m?QyzʞGJ<0m\\2ײ˾NS#i%kY|pxa~{ ]<=~꽿//Z$$H='U@M'e?//W??U)L"z*{,{/g0,xOSKQk@JWF0c<|-~'O/?I[p) T V$mǼ2{ ]ܻABߗ)-y νz7|Hf?޴y@"Q>t4vǏl,{Os2_so\ާz~#;<à-L~:q=c_^^w# ׬tďY%G/^O/z~+oORq^{`c~C=y꟧OSEQkNJWH0c<|'HOSy{I[z^R/GX8esJ|wt@QʒUثTV5;5wl!GW8&~{֗P]GssU rF'H*v*?Y7Y+q+Aw;' AWbR_Mv |=DJ?'2%;~Xibv*yhGxlֻ5lfNNrn]v*UF * UFV#ݽ\*WהBP} w8><z7CNjM)CW^8c'>)tzrt]>×?E˒. ^q(էU܏u\G^Ç!89Jtf܌xr1]1w,y\9pZUZ}cN};~8zSM)R%<2]J}c^?WǏ:qھxGsuVjN埢=>\Rg;~c%޿m;~c%3Ͻw|>m'. ^n8VYv'܏u\GE<>*}4$ZSO2]Kza˗բߗ)ua=ˈo7Cƈ֜b5tc;Η^?VGib]z)!G?{|;nJ}VQk/~c;ׯ?^~ӿu߷^=q׻˧sGi׬_DŽw/ǯ^>~iOCJ8%Akܿөӹ._VQk!HN>φ<#|y8կњo?TN>S:1ݼqOKSӗˢZ.\pZqF:xӪ?>5> M)&ZS6c;|RyKcϟբI˂ךj xGrß?EϛI˂כ,էV]DŽw#ƝWo3CÊJpCp;c;|Rza˗բߗ)ua=ˈo7CNJ-=4c:!>c'שտ}kXWj^Hz~x;ǧ^_.~өOJ zEo xr?z;YaZܾ>O{|w;n,_DŽw/ǯ^>~iOCJ8%Akܿөӹ._VQk!HN>φ<#|y8կњo?TN>S:1ݼqOKSӗˢ}Z.\pZqF:x~}kE8}R>>SLFmǀw'.}Bǟ?EϚ˂ךj xGsu\GsܳVÇJpfR%<2]J}c^?W:qھ>4W>?Ei|=?ziOO.ߣ9\-yZue؜xGrO{7NXoֿ;~xDŽw/ǧ^_.,?_W}c|;c;ׯ?^FiԧaS^ _dq>*WהBP} xGrq׿ϫ_4<~.}4 ]ztcx;ΗN/Eߣ9s\+ZuQ=ˈ8p<8|}4pB{sH{ig#%jϯ?DiY1zYH}YbXi  }mGn?⽽5$Y qozՏ'ů;uo|>lg42v*UثWb]iKEf&pj#Zm`uKk%`F=0%GM'!$$ i}~8,F2KԹ x˚ܾy2 (2L#X˚aYm,fiMǐ3$H"O`%y =xI-5D|@BvԎe`hj[%ثT[\o[u2GB쐡v RH]X6-Fʖ[ |[Tm?yDR1V=~ejBm@hZ^m?8@JXeqŽ+"S˟~\ʉne-fNVPMr5aQ3(~`XQ4t9!K{7hn9zODy8\wKB7X@>L#}>>7#yv*UتW0j+%:ܘ8Wǣwbv*yt'ȱr.zS~ӓOsun]v*UثWb]v*UثWb]v*UثWb]v*UثWbRmpҚ&k'/d90l݊I?447_첯w~_)38\b]v*UثWb]v*X#z_Xc>>|H޻ʧv=n|7õO1Z;v*UثWb]v*UثWb]v*UثWbRkҥ[2'\1)bv*UثWb]v*UثWb]v*UثWb]v*eg D2)( WKS"%̬9) -dywIui 2+TҀyd$2ϕ&c*~>㊤_aItWOR]s!y_ˆzӓ2 +QIq X@܀j  zeDQ 4Q=;v*U& *w~_Wt>?eY9?H?w8uOCս_ZLj O_ʟgn\RY 7U*k}OrZ᫿[Ѭ\d|azv1}[0[7b]Ku_3oH8umZOQ("kJ\UR[ҬY[!l:vTWfRm}ֳrqeF $lI_uǝ4mItI^Ŧ A"@Xh{W-ŌKrDG oKܺNQY-cz--: >@( dUت]iZ w2\~ fF,¸'>1*ڔW㉆mf\&q<3B\]<M}5|y(!,-.a9#7LQV$o8͊/VyW--o7Z}V#8fHؒ.IN!V H.UJQiG9sukVJZ.zOBbwxw;' AWbVK )W 1¥_YMgv 9KL)k;M[M{<_L@ɬ jN=~=?;צ=iy*>[?zǮ=>i(οWgv}O{~˦}hy+_VvzN}z|CVkǴֽM/K/l>4z?z}W'}-_W|4)ou~uZ>/KߗG=^JGz}[vս?zǦ=>i(_t߬zv}O{~ˮ}hy+S>[Cכ>n=7OH:z"N+}n>8w޽p?5y6yO`9/ir:wi?y9xkEMiz=}ޯǏO}JպY׫{^NX~n>=>i(SοWcЊO>?Kwl>4z_nWqzoԥO9#};`zGP5KԸrrj}5,\NpǏ^k}^Ko-W4j'_pz|oڧOZ7__}KRm;:=ۈl縑ŴJW[n[DKDiVثT6OXǧJſr\Sv*UثWb]v*UثWb~}OC֟WN MOmSv:./ -q}@sCޞeιثWb]v*UثWb]v*UثWb\HM1WC\UتW_ݻ}@%ZOc%dAyZ=H4"7Ɉ6hcۦV*UثWb]v*UثWb]v*UثWb]VM6DGtɣ.y$Tj1WMokir7 vhѩe$_^D3NT-'F9--^ $vcE+kM(J=`t=it[5_3jjxxq2J=s7mԯDZ7p*a^Uz!//m[IhL+MT(fnU;'|#NP ]K޵խ3H B/x;;6vgZmhzM%K O)W"~*UتM &kkKu={Y9?I_!M/_5W>4}Z}my;8|,utnX%~fK}g׬|~bxfN^={rkJt?6<㪂UثO:u *?UUPLUتG}[Mz׭נeIZG/A]>d~_PO2n]v*O0-J* 3fWׇ?c4VN]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثT ?Ŭi'՗ӯr~U_~'ʿMثWb]v*UثWb]׭KG>ޯp=&6e߶U-ׇzG}ܛ Wb]v*UثWb]v*UثWbXO/XAw*Rw,G*u1y8. mg=m$tuFeWTTkLV=V~l\=vI<)nU2_o2mLo]eCdQҵFU Y@vdù ?[fV\) rmj7w*:?`o}'1Y1;o)^cG),l'ҝl݊v*UتK#6+A#G}=f`?sk5#aI5BPQAp/ ~UOTE% W/ǖP6Czkgň>)wa˻w{7 ͽ+=,N*4bh,S"]AjZb^y M'#S.ØcO1BW r]J x{>FK.Q'*7۫iM4$`Bh%6DXTʎ9&]J=?z5)#X?}to:dȱ!FQ(DȫWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*ч_o??8WֿSS?K7N4Ww]S׻v*UثWb]v*UثT^~}i?R٧j/܋.NO>; YjB?9zw:b]v*UثWb]v*UثWb]Ai6wJGtI0ɔdG&;7ZI*CoMxt[U]0v"yO2kZY-u O`[O) ph[\ou0IOLLk$OD+[לh9^AR#C|gw{疸I,݃@#K$KJ9}(Yc%تah)QdR<8JVEe0I7 Cr5|*iZֽr]@kXXL-9d]<>iwdQGI#E٫T 6MG~оߣ~$x}3F+Ƅay~h6ikjdiGFgfM;T f eFB\&ӿUȍ7A"TzIF9e$Sd)9mHkkv1 W Ԩ55Tҋ]v*UثWb%c2Lc vqUWOA#⨬UثWb\@ =F*xfoc3?yfVy 8_Xa&[hw&DjScF&&&^,H=16iw6<oDr`?i>c)r%cʚe4PhZ(V#FiIdvO+>*,IS 65+WR Z"$HPVb^$:PHT\>pw:dw%xynp+=Oz^>$o =!_AA_mypX?'c]\JЗVǭXNHůuo|>{$ ثUQHU'A~"zSƼz{P6+ZM1 .zQ0>C3  $~wyN"(bXP &6Jt~N@ (+4{VsB|E9$VaIWo Y̭Wb]EVL s[JdfVD>E{\dUثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]#އFzc?s7ʿ5n7KD-p]v*UثWb]v*UتOĽ rt➓}O*>ŹJr?'kUثWb]v*UثWb]v*Uت6(iHq:|#'v*DbRBzs^Z;dX  {c:PӚX3#ʌ9 y1_,D2(XÍ؀[̹b<c{'VVYCkpE~y!V@+dUثU -B{+yT2:0+)؃V+m!4Hh"B(XC:;/DS|JAiXj6LLh:+nG4}^ CMC^_ZVwTCAQ,NhiZե~J'w-dPvN]*0w[鷩=rĖLx8N<PP]pߚE:E@L(Z4O aȃZצeˊ.*,WѬ. 颰N~"Ua:b]v*cPJ۟fWՇ?WE?,g(qfo?j]yH c޹ǀW}߭$*LvR[>ʣ/##9GO2#um=iR._g<+Wpo`qUlU$׌?t>f.ZOԹxw97Al'݆,H/ǹOC$rZz?!)lwqI:/ UJ>x3y:ΟW cqIPqO=ćc >d6Ht-[^L!&>LXvZU̯?Z-fukw*^ib(o= L&k;";vlU9m.%Pڭ-c8 0Z󷣖g[`zTWb_~ mh~ej)baEO-l\X85dv*]vNMBO$_\FJ9n-#Q )g%fPӏ\U4^y5]yoWM-XZͱĒ#85)k_]Z{ ݦ8L3 "dq>gZ K4]v*U*SG;D!R/VkUqiY>{Mfg~Ja[(HP('d"Ru")Hۋhõ@#,Ie^6=2A HBQ/$h7-,z6PO#8 +<PoMq:Ou$^x_Q*C+۾*oQSZX^T7̱&AƔ=7^2Ecoɯ+–WWQ撲#˚B|t_I㓺m//hz>0P"$^N+׭O|eͭ&XA q\ih _i3YKjDK"vc@8H>Ozd",?Vm=+e!f2(I^`~DSoiya*2[7?< <2cͺuшŒro8'$8M&"=x0n&CZ<cZkPX}_Dom:zi-SZb/4yWյ;Yt/ypV hH9K2d18RH:-tK8yre1_d%2QN$)oQVw?g~^q*iX;v*UثWb]v*UثT\44M[_v][/C{Sv*UثWb]v*UثWb]v*UyY^P2JrH6T!дeIE3rAQ\6V?zG嗌8+>Y?y"?|5ԻSX"B;eO|gڶ{ŸC;9RyJ'׉ߟX}J}3R{ "]KX(ʹ/pX47 I!{rM[C5WA0TmmPB[~ov{jz^u"̰Danbp%#VWT!O#}LOF͐u/WYjB?VXbޡC)fx5m>An>Ŀ1vmV(pb/Zf_}0{ 5̜wN^+ْy}?6fkBOc"Ӣ+oNkeӛfP>~Bڋp#lA%a)jSfH{emLbGn}y.纓7Hm2~ { 61P $u]?Iu 4 lR=~eybM9rx*# Z@~W ($†Hx+*-/>[Mz*Q)E_4 _;~RI>zo^sإwS/綹im5%IriG;J'OmZM PvA6QG%4<. 9CC* yy%ߓZVmkGS">>0ZOMH #ӿ)|?5隶o=ֵi k Dw#7N:p$%X)0 K(Ă{]y䶉{_2y1jWzm?oGH]Q6*m?!m.m/5CsQ$gѩtJ?*oUu=>&דFVH4ܬʒs6l1#TME2y\t{TkM(;ML6̊4WraYq؁h:ezpξ $4j7M<w!Mm<(zUFm7QŦa."II`AJNAzҙ )я,nS ;K8D,Qw'=I9$nF@Tz0^[zk[kU~|nc.t:3[^)[8 ٗŜQ=HCGdh-_.OofNX=֋M!IeUC++ VG|dv*U*>GHaoB(䏏3Qz޻tʧv/ok$c=&_Z#'VO̔ExB7Wo~,aK):qUru{.IZ>j@F@W'a>IATYY Ze9X?WN \?i"8!PDG@%#"IY/ȫT&o-Α}o4*̄ Ϲ_;yw[Ϛ>gt[x博'F( P]~C~_/mKX5 =JoJϥT$vq}5YG2jX`ŕJ72:f+Kt>NCY_/廝2;JzŴ(I$B|*=6lUI}2$fPVUԴ(5]$\C-1j/[[J5L&N E Q[HtCVVGiM2c9PIF.~DbWb]v*j?ZBrV3t+mo_,XKNrn]v*UتU_X#eW )?2z(|G~%5VN]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*U*Y7_ |1}WO{ӷ٧W^_7oKk8N]v*UثWb]v*U%J~~<f! *Ga/C{ Z݊v*UثWb]v*UثWb]I߬j?/O^CM4:U=gu~ϨM#/1> RT능yak8w\LӁQe39;5^^:̾Oז$'b BF Ss.lI\^qkk+y"8fA2trO0=E*`3ܲRkY>+3 ! ]Kq0 Dx7J嚘#d~Pb]ATPCD_銷H(63Ci7>G2yeA~N5 _!ȇCeߘ6?E;k:g_AW%o%մڋkwj:qF*ɂpAMpɸjܠ1^?wգIj/xs5A6A)$SEIid_@~}m]I9z/_ASwPS)\Qh,\ {?NBr2ȭ@ܯژq?g >~ű_)t{N^y!pkDzާXw{eap݂@NV.2hHyTWcA]2q$$-fu+wyB@5osj&6~bys;Eyշk wGjZm3 P=*()iv7w?9/ͥ躃 V.}R[NPPT/ +1TΟ>Re7^aYoNgQvLU+'ѫKo2.}o-T,ʼY*y̚7;sZe*Ė`*yA^mW"L) SlUثWb]cGaw}oeu%xj(dxݭWs%*^Y`:f W,SDB$R(xBYXTF]Q2JEDjX߈*ƿ-9J]}?9|S|v*UثWb]v*UثWb]v*Uت٢Ybx$RMPZnT({?o[xwdo1{+O/^[kVc2 ̔%xxz!G,Rcup6%H?"1w0HpAفiZ.."ax#r*tf,ǒ"dQ:"ۢWBVڇ|2dO)Cac46E3&ߙ> zes7ok>R n%GH?_X!K)^;9'k?1-<#y A9ZgWRu*A}<Wట'77u^{;44K{>gݼ7wux7B K{ nOE-, k(%ԣ%ɨCh`hq$B(^r|n4s}Z+HoNe`d ,uVVPC+ 7Wb]~]^Yس3+Wc1Y;v**` BƟhZ]H7#p.f}G%5 RXwrYټY)J*UثWb]D>=}oPeOXKN2n]v*UثT[ڋ|9 $Nedb~Xibv*UثW=AwͿku]Xi( mm-H^0SOs@nKMZ5;SdbE(_QЌU俔ίͺɹ1T䎇e}7B,<ǣj6<'m%Z) 1Uߚu7j]k. a$zO*GJm1k' <)N>ibqywAK SO!Y"b QDQ*=ZkJENy )nA$w<q87?4mSZ5:12xƎG/(i-3SZߕ4%<ԃҚigARR2sU_$󇒿.coKGt#eoP,<y?wk3J}R'lT}s?>yok_'}BR:y/=Q^DXyk]*wn|+y[< 挓Oi^s qBRZU uR/%ծIO· <6;N*!Rت+ߘe>B5ߚ.qgeh$?ٛoU)o/̿$E?0o/0 -oJYa0]؎x-*abͺggmuFfVJ,`@⩧هWN󝾙wa虬,C X%%A,vK?(|y^a.ljV֠²Z0ZT\տ#4 b'ʷ2D>T*~my~mo2y},OLy{UH٣W *bOu-/`.G*|B7K4?6~wIo4^-HЧ.6]D@Y#eXJ|4ח?9KκXh&ZU2^Z1͙xcVkmGCܯiR/%dKz8g8k+=Ikv*UتT>(oR?T_}Zw4-<\~|U_x~Mr ثWb]v*UثWb]WBr~_iݷ[߅%Cx'ysv*UثWb]v*UثWb]v*UثWbDSU2Ӝ^\fG{2O)b2v*K {j6KҔ;vz2JU@۹XZ_kwD*+ q7޹73/~mHnl%fD Uv.݉ћg^VkSu!!x+n[Rwv*UثWb]ʬXVe;*k?(i򗗢 HoVBc\ThSl83z~ߒЗKJ_,ӭ?ICm'j~Xrl}\;]TM[AOvo%Zadsˆ=$#aVvZDZۢPWv*U_NԵOZ ou4J\[Ɉ߉OLUE<6W>^50Fx_zo4>"}VH߼MO6'M#?&yfYiKp=b2ꦪ ;rثWb3xMi1ݴv!Y?b3^{4YLi`(*{fN;/ 5ɐhj<s;jKG^@73Hj3_'^EմYtq-Et6rGv*U"տKսO/Az:u+)\QNEf*U_Pzoj8s+,Wt|?g >~Űs//4-pm?QOBR9 0e]8ʿ!ف~l 'ɍHyVP.d7ZMRKuee |*-r14[a*)t:3Kc\7REw7 gՇ$'8⧗qã,u'c .;,0.Y&č'']\bY1E I H#5 jUUb]]{P?Nd~Wb]v*U*ׇڒ4|K̭/8}˽5Q9ثWb_=~SyKW/|rMơ&Fz>| :U?d旫ê"?YH4.4Hjnzyߛ<~u~jsVwe}nx7ǙZӐ*_:gs䉆 yW-m`$֧v|UΗ>Jz>FaRrH*.;)mtR)IjX'qTKO404mxY@>ِ#* 뷎*ʖ4r8,֬o!innbrKQ`U&u9 i>~!򝶘.mx,' g#wQPx -mۋo::S,i#Fŷ|} rއ?̏6^fLq^z4=RZ:wߔ1s;e]Sfa "C,ͿB*]ͺkZzWx[[{eoÒr1ֽ*SǜEyS@m>( wv q䠶c>aFԴ 45:)nxnn~{튧cə1J:?D) qq Z'*w8{F"jSWYn͛kijԖWNJ>,USZ%u0HZ/t/z )s o!RG_CLnq۵0#YS9".(*]cQ)15}2j~\аy#As銤u O=J_4Xj>BX-XAB@zb DEMVfYVo_/h:sTiQ!)/j::n[ѩiZޞmk3؛ybDTPSY<~}j2׍5żI=$$<"⬛F_;T:-#XldN^Ј'OsmQYV_}!Xa=e=ART*UثWb[n?F~ >?ק_Uv:r?; }\^|<˝sWb]v*UثWb]Ju_鉸}e_J)7µ޻wʲs;K^KzȎQ>-p]v*UثWb]v*UثWb]v*`(ܓ U'=.NS5X$.JA=2t/?opA)6v[@8Q}|&C9e +dثU(E$$ UUQE**UثWb]v*2bRN 4d IU5t`!TK̼?y󏿻;n#'b]v*X6E*;pAMiIܱki+:o9eg|/(#>؍N3 WbR "ig7'`εcހHBDuWӬX1!$N$ ''v*U*GI~a@#7"zes7ok>RGritg?ܯX?_X!K)^;9'9kI@H}d?_cb'[7b]jG碂OѾ*]3POh]JuDH} #I'RDBfF6i>[yJYӵ;-%m?H}$KģQ @3*1rrW$ʟ:Z5Ramka Ld80^$N4144hPk6 ,pLFΡ%X$h,*lH5Wb7s HH₡h2u嚘I27(KWb]v*jO "enW{j}8% ثWb]v*xc!rU(0FF$P:6 {6kiOeoKC8r4E1dv*U-|0[ ]sLb&U>+}*v7A,ipX8So5/-鷗Ӑ]Ok ;,̤*F[L޵mH 84?,U "3nhZ\I%< (Gӊ"F*ME:E}8bqPI늻X4}j^BBKkXSIVlF*@G '[luP=żr2 T/*hZ%4m>(!X$Hp=W}TC|u ~|AY9=BS=o@&ִ}J͍MI*Tt<\T/|-,K6LfP qTV]k jRbFGCQw4]. dKHR.GŸQVie7Ʊ'ۑVjnqT:t}F^BKY1GʻNl4/Oӣ,m"ӡCVq"J7RO΅iBLⵣjLU ~Z~^P__7۹'ViuvZ}Vvq Eo,q%1TȚ~ՏmYc}I/&D0Z{^6keEefζ"ƁbBēWb]Cz>On~uyS69q\v*UثWb]v*UثWb=s^Dᑩ/7(ݎ\_@}D#'sv*UثWb]v*UثWb]v*g{}.&IsH*"olU E_YԠ4 Y]XF7zeݰ#TSPFY7cnu *S.`-KS An:4W^lU'<a+qK-y5[LPTsl-H<_P(N%k^hG,+WmسY ^b]HE^ኻv*UثWb]v*Ue$#KENK?Ķq"_d9w6x3cpq73Ee`Ҙr_XzH &<6ҪP@bZtIdpU;pF¥Z;h1&۫ۓ@+OљZAןb;ldUثWbP0_Zm Xnqba+"кU>Ptl;>!\pO{RRH6#þc%ثWb]v*UتE~=_z[GIN^dUԾԯ|%qG7ep +UWH5lL-l _G٘oq?g >~Ű׃)7=yky9nB-X#׶O '73v*UثUxe"1LUWr G:Ŏ=#&W$\1L J2h(?*4K_Ůwu81Mq ŏ$y7J;,B<;e/<<)l uYG#xEDѤhTv9FB/g)h^W.R7C[ xY^G>f559[Zyc^n2k JW3 +]:<BAt ثΟ+꺖Y\YkmXR}jѸKk!o[os9f8wnNU涓m W{k{;xMZm2PuS_՗d[efߛJ=Ǜ.PȬy6VJ#4]v*UتKzc2nh^~_gY0el݊v*UثWbR:EEQAWׇ?c5VN]v*UثWb]v*UثWb]v*UثWb]v*UثWb]IX?2}cu]e;xbx'\>'xV\띊v*UثWb]v*UتU}c}c"HM?׺o]eS7KkMr ثWb]v*UثWb]v*Uت#X91U94o7$l>d<گa1⬍ fqy_N4-l.dm|*z #2bbRzԵج, ҚhT G^};L M3-:sie_Zjq1s ?4|m[^I,V"E$d(YC q\)eKEOk}>~\_Ai/ T_jw___;˝zMש鄬UZ?NĿǧ|'$+fUثWb]FqъGӊb]`?t<=ZZ-(;5+M ce^wq)^Z >PuIatVqط⣱@A(.4#OHӕ^T7wXK$0}vLcn^gs|cs%7Xc) ^$ӈޙᗢ]v*U)oӺ?Wӭǩ%IN?I`y ثWb]v*U-OD+=`u"?쐰̝)|'|Q$)RXX$C#x*chvv*UثWb]v*UثWb]v*UثWb]v*UثWb]v*U)>?r{tvtW?9-xreWb]v*UثWb]HooSo*|,jWS˛qxYkvεثWb]v*UثWb]v*Uą@7$IPå7h %Ԉ>"~+8ɼW67|u>ӑ$y;vv;rf@NVAF^A2_3tIdaFV$iD ŗW=?;xS2H{K_W$}i}6]]Ns.)@H6UثWb]v*UثWb]`ZEƥGKԾCriS5N 8"Ck?.5QKE1=H3K2Pɞx5"{;\-cjMxvGݺMH$DP_e坭risǥ_G]1Pp{ UwԣŨ%Ku%5 LqWbR3FhWB#x? ~I]V~X:̗jOa>5CJ4XڋX#c ժ垳ݥťw-%y~+)Y* 7?h`T̟~Feԡ0O[ >_ҕ>WWk|~bR?~NtSQ_MOSX,7Uqҽ}9yo ~A_MNa3B2[__7/>9q綩p!Wxw:z}XxK=C2yo38WK=59B:xd++8y.>cq嶩}RoGݿ~׎GzSo.R^澥Oiu_7Qg%__}\8y.Wõw~eKvǤݿ^9ξMXxKk.w׻Uw4V*Mh e~#>vOiu7Sk#ym\-˧pxGkq!ޡE>)pKפr3w"G0Np#W_z>-?k \~w˻g3}:~ҽOM~5=B /Qǿc#,WUrҽ~/ROSO_L/+?;Qx둺^NtS"T:xmOg{'tOwO~c'z~iYq5~.G.G;ҧ]+_MOWyS<6xI./RO&U}_˾?jx_)s^tCNK.8n#xEqnQ켁wIZ`p2.O.6K>T̝[v7je5>7?!Nl+ygǕG(}^Ƨ:~6CΝ?-6oA{eυВ7)}~ƲwK:t.oזO_'Sxǥl:w[l[V׊{xWK:t.> BJsfE?o/nƲw=mڜ&;Y;?ILCzs'r&b:NM8jw0p3uUO.@s*?V_Еyzq=Oԝ낲W0q}3>\W˕tC[ΟVX/?BNYj^}?Kn5wFW1m4_Lx>˟^Goկվ~V1Knڙ*Ʈ=?>.}Wʺw}[W׬~xן'+#=zr5i8Ml9sg[G+OCי/:BMٻ0kp3G~ˑBo9z헭 zq;ShA ?htxqzwȎ]k= 헩ۂބM9_?gpVN::wx0Eo?0_؎=5}3=mo ֖ĝT~qq!u55zOOԷ$z/_IW%k;nGZS?k=5}3ӠF]+Г[v?0VN_:^ܪ G =hyt= 8?L]G~T~?^*$%azzacٗ޸+%s M'>!CPCX֭~ۇ#^lɺ@6J|k3=G{\RV=J=CR{9~m r;3>!+\583V>_U:]{Wb]v*UثWb]J=/Xo[M%zp޾\>nn|7õMm~5'b]v*UثWb]v*yDlKu[64yR x*Ƶ͏$ZApu[{{"prh\"QY^z_̶隁AgErArGӽ1U-jYmԵ[x<5"AC左;e=Ư4ҠaƛS1IK+TIu=^/9?_Y̦ت[iMM(4W_љ8B/6MI/}u9 ~ uL&ϙUGkSғH@C srNq}L+Q),eJ'`uH?зDs^\-coSz>,);-DTZrǿ4|xa]?~qu!JKPǿ L|C_U;-jE tkU(iKY?=??X󿇗O{Sv[ knԍ>YL|COx3zkz5-~(u$o~^=ǧH'aOꞏ q/\~)ۧ)ĝ֘(>o/ۯnQ7Ȱ>#\}? SWG<'Ӝju*K?cPEr9b"/<>b^O=ڙ.3|6ÆH 50k3ϺKSmWo-%#,<8ƅqUUrӾ/zՋsfzK#ͫ7 o뇗1Ϻ?:_7(yzKtke_Il>*a~@_.Gjߦuz_.xzC}^a7ȵV7G鉭F<Ǚ\~/\擃!7jt4~Kx/X=V/STrO^3;׭0|X~S_Q=9s3,c1rn2' 枟/a_GtWsQ-(iKqX?=~S{Qws[C]Ԉ%$Zrǿ4|<?.?m8뺐%zj?ᩏz>(?X󿋟O/Xз@Zǿ4|c]?~ZuLF[!._(k[sH~4?=O{qwsP H9L>$Ng,w^,9Q<ثkP?<=x!yEDŽy~xwJ>!Eq߉F ˜GA}_y8s~5N%_Ig,|U\.\#LdE"#֬\}7O=ڙ.3|6ÆH 50k3ϺW޷ SqrbNlNm.*a\U~U|\tOz?n=?^.~گ_{S%oXp߉ߝ.}{ "~~>.=Pr /NWW˗ND~ϣ&.>Oڙ.3|6ÆH5;\>PW@ss,-^,>/ o:=/<=yyEDŽQIxJQL\y tG;*RV6}.:'50cc?.}?hkSNP?o=oU;yt?i]ԇ).Pǿ L|CG?\}5"~(z\ ~{-qOO)V?^eAݓr4~YL|CO3zƷB~ d8μ`? =ǧHS?>+^ľ(yrnvZ`O_ŗx]F(?bCCGu| ޽*0?~$~ߘ4.r>W ?7\ⓂE׵:5^,>/ȋ2r>jo"sV.>ͧULG_a~$oߘ5˙Ho[gyAY}1ۧ6_vz|YWy6Gx /ʯ!˾?/-z1sxrԆjU@^zV(9z_Otz|YWy~oqqW r˧}?L_gsejXx3|{S%oXp߉u˘JWWG(>i7ۯ ^3|_a~$~k~dя.qzRT=OW|%C˜px9DvJ!~Kx/Xh$5u>a֯ 7!n8K$6@Oq^,ђaFX0!F*J0+[?fVM/sM3T6iڥ~mekFV=1WEM>e=WB!%]y([I1}_zUqeZ&\F\tk=CB|2,"G(~`7CѪn\>i/U4/вEqw]yv4Պ?BaC'*X(P79VQE0ʳq*i!/k)RL|-rv*UثWb]v*UثWb^jOײ…_Zc1Y;q Կ3rϠ\\s*!h0JQ*|M/~]ү/Ⱦ_b4QML*A SWQօwmZNc4='1Yo׀ZLMH͈su]mh=rN~8ZnyV eN* v*UثT^|94_EăhgNNO>; Yj\?9|S׻v*UثWb]v*UثWb]v*UثWb]zM=zޓD gÿ]_r_ j4'b]v*UثWbjK6T莒۟ c<f ^;8n">$ $bz(*v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*Ƶ֫r>{9T>~Źqr/.w^iZ;v*UتU}g}gzރDJ}ݎnn|7õMuIX;v*UثWb]v*UثU{;gn1F*ORO@I2xʇ4ZO}/MY.*MR?xߴ~4yg稜kP5TS\J3v*UĀ &u8DפA$jF4rU ݲ1pC4SFHU]MAv*ҘCMXte>8AAoϧ(T.[ɿ2MaxI'rI>9I6Mb]v*UثWb]v*U+O-%H~1M3VU {]=6;Cs9QQFe5m ũwSb*67?ݮ㏵&s/9w~IʲBXUXpsdv*UتOB-?@ t][/C{ Z;v*UثWb]v*UثWb]v*UثWb]zտĺZ^4܎^}}GLu]]kDWC̹;v*UثWb]v*hWia׷Tj_̭G1x1Y;v*UثWb]v*ԵM7K{J+8\HFU܁c'bEi]GCu5K GZU!NNcH&*H%Ex\E6"+HE}d6,^/NPPDL20y 锸UثWb]v*UثWb]v*UثWb]v*UثWb&~׸|X=N-3!oŔ5W//\׻v*UتE~=_[GIN^pө}^NJ.nEe*DW>={:b]v*UثWb]R寣$z1qR cMjY.tʔOm1{^I Q~b786N]C3\AMl#F]T߲qW?Ϳ`^IpwPoymQ?"(z4`]d[vF,Auk&Gy+˷u#Zt6-^Tx"knF피zNe)̙fHcTߜ4/0hŕ¬I_Jb#74>?Nr^UثWb]v*UثWb]v*UثWb]v*j_X9zXkqzRƐwѷ&gC|AՂO?<Wb]v*UثWbVXd,m.} C1)bv*UثWb]v*U~rj]i׭iAt% Mwjц pr#*|]_5mg̖ }̶uF2"m̈o+כ~g/25J=?QGOKW4_!>@|~Y) ,(?(2~i\VFW Kx]]qFG<ׁ]v*UثWb]v*UثWb]v*UثWb]J4[γK^C=!_JU[읲}R_s5cgmN]v*UثWb]k[Ϛt]"UѬ ;˙o&5Hr*Ybky@,z'^SiPԍFz$ U\tӵ[-O:T:WwsjЗЪHYCo?1O@s8qu>ȷ0i6=%߭ mGePןM~G\ѵ+4k{w\@2hWXXɭ'8ab]v*UĀ &nIPw"/YV^F> S튆iǛ4\I+v<-WTUUF|7~^L h#A *=h»M+V%Yձ,5r%dӊ'e\4 (%*GaAd 8#s>,$A2\:QT(kLS'9d ثWb]v*UثWb]v*UثWb]v*UثWbR=?~ASoNzu'c1_T;'sv*UثT_?Kh>oz+_O&>)\Qu >~̹;v*UثWb]v*yWLM2~ӭӹdi9-*Mcb>of5kcJviNbgɵOb:d U :lﴨWhh =I -RwȪuJ<Է'$KBTǦ*˱Wb]v*o;k{ eCZ?T1Y;v*UثWb]v*UثWb]v*U#5Y"K{{PmTʇZ̜;OրQrv*VYoPIHX BF&0.4Ps%uy( KH]'ثWb]5)}L[^0 >ǖ+Q^ث(E{mi-KpE RS6G4iKXƩXn5\ƫ8 a<6UNfO{ܾ8wߕW!e"H K3c'.|ԧ`8o;,dҬe{-aLj8/Amk Τ xG'Zhmkxr)Τ$FbI*I<јU'SE* Qp?o)y{Y9?I_?O|z'kUثWb]v*UثWb]v*UثWb]v*^ӭǫΑެ-MN*>?77x9.$}%>wϒmN]v*UثWb]Ju>܁y?s+/e?sMsWb]v*UثTum 33?dǚsl/[Y}=QJӑ%UkrQ&peɫ-ra#Te,Z y< b]v*UثWb]v*UثWb]v*UثWbR+5SqSdOA__mB Ѻ$򮛦kUثWbF37\$)OIk+wd={%$O&kUثWb]v*UثTMOԧE[k*{ Y>C2z !@b77FN]v*UثT2YZ̨s/Ǫiv*UثWb]v*UثWb]KuGahooIHy/ޙ9}1{ FZim (*afR2<@U*tE  Mj<4ov]1[k5hG1_Q.;O1䎛Um!gicVs յ~"V|*v*UثWb]v*UتKȠ&kvb1ӯl'݆,<_9׻v*UثWb]v*UثWb]v*UثWb]Grzۼt+>=}*O; 5_/:XreثWb]v*UثWb/bA  ۭ}\P#9cy"ثWb]A>,vV,/eDŽK!ߔ,ZצXt~Ȱsκܖ6Z.5նY]s̾mJ$ NX42BS.<Ǫa6VKqkze*"P~Ş}NS&ֵSIcsߤ.g +@ ơ, ]8qWb]v*UثWb]v*UثWb]v*UثWbo=#oz<?d'Q)\R|^⪕X}_Fsv*UثT^~й}i?Rj/܋-Onwr}Q~)hWR!{Ӽ׻v*UثWb]v*:wc`LmЎ;VIG̝4ĠEo  e$) v*UثWb]sKmi72bv*UثWb]v*UثWb]Y4AK3]`*=H.I! } OJba&١30;0̜"97dv*7|}拍;aBAM>֎JbټaԆ\ l+!5OF i}Y]:DaҖp&IěTǬKsz:\++#BLn2>R^GuؠQQjZ4AUvfWb]v*UثWbRhKOF%=;ei76ש۾U}ߊszˇ?}Zv*UثWbM_Wt}2TOC%̆:_ߓ_6X?ӊ>Wm^EH!bXF)j6 U]v*UثWb]v*UتQ?OK&[?j}Tzv oIIZv*UثWb]v*Mc6ǔt{:][mjRU/*ky7,JmZ-oHeKI xƁ<<92r߆»S$d<i&-:iT$Z[2PcU$W*iM1Wb]v*UثWb]v*UثWb]v*UثWbVGԋ%2|l\+7Qcuwa]\v*UثT[2 OFd n[ ZzM;?:ʲsn~<_OxG=-pv*UثWbX%ֻzX_-33[]:3v#y~j~Xy:~餽z5Xק}bq/eH7ER- ]YbN//<{L[ 2R5 {`7wHHV:튡<9ŻYj =\띊v*UثTΙsw!Jt=A1Wߗ~I򷘼m": BIEʒ1⯧<[;5.m$.\eU]v*UثWb]v*UتGne#Y7^=HAn(:7LdqNM>R~WXeιثWb]v*UثT5Η]^Z^\[G-݃;YN /(u䦆V9y]yQLKqqJ QR65E 3*1.C˽^d-Μw6O-.[xqȫU@d )3Ӭ>{m4};-dqe R!εثWb]v*U!};ktZaӥEp̛l_Q H>,Ccq R]m #a?0 ^cu\\2;`z)J*+].UԴXl&1RGñ*1Wb]v*y~P֭M&A +TE'*q]KC4fLO-_@WOy!4]ڝqT~[}~xm+N>>]Y%i(Eqߍ{ cq=BեAKdէAjBU܏ U]V_/-Aتav*UثWb]v*UثWb&-jV@WM| 456P@|á˧jE1x)ڰH7&F Uj204P w\д["O`$.$^,w$$)ݝv,6Ѭ0BơUTv UWv*UتSy Q:xOYoǪmv*UثWb]v*U'EP`rP*7KRo]eY98}=dG@}^N2ثWb]v*wsR Y*_XJu)M=  O1ViŤWt?M!4"yV~|[I+FF*Wb]v*UثWb]v*j?X9zXkqzRƐwѷ&gC|AՃ|wϢk8N]v*UثWb]uk-H=c=9wv%/HܾUtmVbRjIvv'#)H*V #mЂ:2#GH z|}&_k)wN{/okcGM ثWb]D6F `ܓ?ZC0O c7?WWq]&f|9 2 \P"<|7bYVAf^NM=ܿI 6eg(CRUثWb]v*U-y/;cPH>?jv Brr n+ebHR@J`_Pnk^Q(}(x]3Oivy#̉z}CދNs.]v*UثWb]v*UثTvdǼzp$<|bS'em>,`O *WāNC.C9Vb]v*떲`^lx!Us#M1;b9:#U1= A]v*UثWb]v*k+rKNkU}s/NrثWb]v*e9]~bq3=VjCPuYְK5ۤVѩiTnK/g[џ@l_&YkoU8Wb]v*UثWb]I5CI=Zz^2I/C*mg\q7z.srιثWb]v*Uت6I<(BD̪_4ݡKo u7odgÏ!91bv*UDu(Qb0J.b^ZK'xf_s}[OM-Ijb&\*iMrQ醴i>g'rG{Z 莴;hQ(9&g##̤\v*UثT%毦H\αTOһR<4L6ӬR NxA bG6w2 5M=Đݫq)(d+͓Q|N]yiu't[U䣏OY )M_}<;ߗ0^f+[µeEO"$9 v;d\g$εBg HE6ڙ^*UثWb]c^b<ͧjJQoY^my[Z(uP5ւgV(!Wom^=wM̫ZOk{]bGQ>iyolu{%ݵ,!?W^$R&/'4 oM6yy+ymDNHQ[fۨX$?NndI,"EkrVXpowvM.a1@QdJ?&MnY~[mdҽ)>$20SQN܇]Ǿc̻v*UثWb~?C})Yk z7 @FN:|UR^weιثWbR=-??C$]>SnNJ⏽踼, > eιثWb^i/7MIMHAh@xw JֵPPڇ:ђIW*($IB8 Q﹢"koͦ$zi3Go#[qRRyW"Tfo(7L^_YӤPUdPEs4#AXٍ(c WsU; v*UثWb]v*YRK󽭙k{/~?̼!RXoU!~r/qp0;='P{QKK>!q'((.]v*UثWb]v*UتU}YYɇ"D2zq]Xibv*UثWb]:WޘvZ\Q/?b;ldUثWb]v*UثT[ u=/ZZ=S/G~D-pv*UثWbPږav]X\9#⌬b1V3PXyjչJUO/]v*UثWb]v*UتSzߧt~[Wӝ#X[U?|nn r]_Il&XXT?`թLɎn(zzآ6QZǟM.=OXDjzW2E*|*'z比ٮ]^x^2Z~Q&Ǐ+2ht$:faiږ:D'x'v*UثV!- h:XlQO|(n|'bve qa&˯g.+)#\zVAA_ Cjw3;nO/6w2įsr QB4j<^tf9Z]v*UثT~IV̤6ToHVN'Fእr V4E *אrᄖ'O4{cɏ2Vו ^M$QN8TX= d]R{ H I3zaJѓ3}ր2 v*|k}KWޙI zף3,gj4"%9oNɌdˠE B}A-]v*UتS}cƱ}c!}Xc*zB+; _su>:7D>UneWb]:ϯKGnYoWҸHR{o2Wz*1{-xy.'rm.]v*UUe*2){U #J(?RLUB*@[]v*UثWbTn-mP=īcER|u'劥Z %)DYyxSD_24K$^1D{ s2RAT/t9oo#yq3wfj1T\ݽ Z[5ܶ*!ZS\d+_IAR/'^@:́q/;r\SAyF%7󗔯4{Mf}*ٽ;"h#}7~!=*qv*UثWb]v*Uت\m0_Hp O$"O&Q<~Y&WHP22ݷ,8H;9b]v*UyOe3Ru+yn`YC *;7'.1Vw_ZՖi=suF2F`5SS Э&Pf&6Xo[7yR񤀰*|2kھ\EVSscS M*qWb]v*UثWb.SȠctyܴ _ECi^VO>Ż Yy#xs?'Ykv*UثWb]v*UثWb]v*UثWb]IuaB"+uydWӜ|0]U??vk^u >/.iZ݊v*UثWb{FՕ'+1@zYDJ|tjg4-..I并-'3LBZF@%2xI'uM ?^=6-OD0EͩI,O7Vf7C G-?v3HҮobӭbלj)Mey1J)dZ]`Vӣ(RubxLO8V%Ϡ-Or.O JGYUgeiǏ3*6s1H-pLAb|\A(w3o.j:-yI\KϝqrOۡ5y[ DV:kM' ɰQ%) @'k` HЅ!#Ѱc觠̗, ǣP_c c~htzkM3˭iVByM6e57K <Ѩڧka~1Asp݂ajhr{~.\`γ*WvdXZF A\UJ-WLE+dTYzQXWb]z'տ`z<?d'Q)\Ru|^⪕X}_Fsv*UثT^J\En}Em9>tweG)?=\띊v*UثWb]v*UثWb^e;7zWioh,UxB7GHXr- VXNȅIӢ\5-:I 졢}*&̺}[K.Që=6gޙ V{{+|H,e1YW[H5moWqw$Z+Wkkvhm#>]v*Uث0?*4BK].J7Gsq$mJ"|+[(^(As9}P?6?^~.T[ , ȇj0ʲ`9ԐQYR]%eQV5&#!9kI˿/{ҵt1Ig/"KP beͲ 8|_ɟZo:jb4yLΊx*QJ(=rD`(~hK3 䘫twS_ݺUL9nl%/.s&vEhW!' tJf<Qe62ZC7 Yґ}bBaj T:33CR$i正~󍘲i[Mx a dDHEiv6M#[FU;3eN$DE`CWb]bgZNmK:m XF+1JeHu[ǰ' ecȸ{S1\6_v*U*_W~zzD>6Z}m?s ѺW򮉮X;v*UتQ?I}N?Yn|.Vi7ی8 t*>ŹJ]}?9|v*UثWb]v*UثWb]bk<ɨ[jsiڥ/jm },+X->" MBF=>L^x71Y% j>S,u/\eGg LLi iͺ]mM|2*򕮹k!oH6|25]E[<}_LR;Ҹ3]n쥞h1T#)M`ۊmTԤNCT'ޝѹy "@׋e@)Pb]v*UثWbR,hZksR]=&–2ݐoJoNdZt+K 9ó%YZs^fL3(x (?'OcDI`-mi418 7u=XU9ɧ$ʹ=M{=L"X-an(rbIrv*UثWb]ܨ[Pg#K4xlB4W1xЏMOINH2`ӜKWb]v*UثWb&нOG֟nFLڛr}Q=G~Zr?9rw:b]v*UثWb]v*UثWb]v*UثTU ! $n}?oU??/]y9kUثWb]/"W7CQkˁe,"ImZ֛aJ#hZUϘ SK%j &[3"DCv5ZTeD=L~WvOmEN%-.բF`nZ4U;c :w,U{E]OPky1 s OOUe)LqWb]v*U+նԴ|/X>Hbz&ثT%czUJJц[<- \$jvZܨme׊З?}$7?>D YVgPN;Fcm*wF8)k7Vu^F&L19S;_wq~;ݖ|URT.u]v*N-Ejn }2gNVO>; y?N^UثWb]v*UثWb]v*U*)e̬N^UJkv*UتQB-Qv)Oh}e :Gʼnt1;v*UثWb]v*UثWb]v*UثWb^cMA?2z>|f+'b]v*UثWbRg%~7o](lwcix|=qgD4Fkz Y%U$Pzx>"δ CxcVZ)$S oҀ31|zWz,Z@kɤx'95+yj*0DՆ~\]h^XM_dԯ4L5͸29V½W cs4ֶ~q*I 20"B|PUثWb]v*UثWb]v*UثWbobvf1YmG:CY<=.IR,$jQi++Wb]v*UثTW-WidN^rڛrW}Ee*@CuO2\UثWb]v*UثWb]v*UثWb]v*4SC꾷Z?7OǧoW_iZ;v*Uت}WMC1GPw]Țv(%PHA{6̬0$tOrckkv(HbQGcfD̲KUCy7鶇 뗼֥}m3R G"_9L xR-KJ$Y-GlB:>|B;GHEh?k7z"X}!y ORx¼ H:6W3.;8N̷I+˭9o$8, Y`{W+'>L5{,^0/9 7٩^wiqtCw/թIq/l1?YZ-u(Ɠ)f5$+fl~\h5X3Ù2A4oa9)2fhFVMjiAo Ak(H@UF(0!~*UBx@ PQtBf&[Twc}f?VC2x2#|쵫z[JanqeAwGB1|^jw-7H1\A׌nrP$ov>_k%ԯX6ZvKC"#̌0),N鮯Eb.AfsHCi) v\s?T'"X7kkf6>b֯/aل_}:6ˠ>=OzœkS\ 7]ɍNnd-}Rdy&zӰR,%+ܤeL%wYK)!C0IH*9^\k?:yܘbpc0/r ҙH&pV_(m.. .r ļ P)޹2h2DӧiTeoPr5;?!n7]Zտ`zʳWZz})rw-_WU oᄅ\]v*U&:4~X_=S/C=v*UثWb]v*UثWb]mgKD_Fյ{-J/OՂnJ༁ڭWQk2yN#R^P#9GBo8]c-ryzX['\q(zd7%Jd[E|v]ZFo{YrͼMVP_%j1SUثWb^r|5 ٚ涛QxCVT~JZ0(;bZypV9̲eBhs.axF鮃kkN;4) I,"Ev_1̸>μ"bO1ڨy=I !B6T @v0MWb]v*UثWb]v*UثWbXߜo}WX6VkI3$%dDHUث]5-cL{1RK5Fdxd^3e.v(wl$Ӡ}u}}>mk &T9ilZgRtH$ߟYv]}n>^+[{N⥛zT.!L]v*UثWbV:GO z o_lwc_ d}5&cUثWb]v*UثWb]v*UثWb]v*j:%xܘ[m?cU??/}'9kUث<5RIFDNQkl+,/*u6sDw~\EEQƿZY$>giSI,d5~ۛ@5m#}.1Tdmti{Ta$W6~Lq>!;*I2y;|6:Ŵv>6³) +%7ߊ\œ=*Z1b|m X91SCʚf%ܵ[{s KwO#2r2k[˲ZIp|ڀtcbvl#GENX}b uזwB cr1"qSs'ʓ\zy-/$b-gk^w> G#e#1qsksoumմ-*#Jp!Sv*U"ni_Ci_ۢ<b(,EOdi4bV$qFH#@YݍrIRu?+Igv 8hcm i8$0nuiMQfraJ _4qO98.[R>Ukh^iDZ~gŵ[˅NKkp2* NmJG~>yy`ƽuoma$ƕw=mlQԺQ9VN[ }q׻]1n֫&FKM#U Ոr6&.Brr%鱥k96:}pg~UO1^YzcIԾlEn Bc(>& sb2$/p貟\õeT*ƌ~Y}1ďm^Vsh\|1)yz_[0Rd86_?ػg]]ƞx6l_bc[JIWC|]kLFRd\>/eߤUzD%a+gSco?'-~!n#OIG2;G4_^ m7ju/`~k7X l3XG[- Y$I58Ȃ6=9c`GQV8FZSuQ(psJ_](|r~cloGO)nK/BiV rm2!9#Y67q_lh9|+^$i֚m5ZC$\h\iL%c%7i_aKt-nR.'|KUvxҙ5Y$jym6c28Z;V[إ⥷$BVJ?4`Wޣ#(Ư(CfgayGY` 2Pފ BO\qӴA7_銢1WbR/?WIOHWDWszm77Qct "v>U5'b]Iuҿ4:~?W/t-sA_ijY w;3(^Kї?+uCz>nۑkܬiܜE I-|ٴ[Ki7:LRUh!Vcý?-Y+'ԗ~55+FX~w*")b)6\"lWv*UثWbR/0}[[>Jr =:ڕ(\^juUvεثWb]v*UثWb]v*UثWb]v*U(ğbq̭ʟms]2Q==x9W^/|v*UG$N2-CO{[e *CU!S!,Fj:<}-&^f.KwPz畵S`EԢ F8aY}SNhhI3'[e; GYZ-SO+䡔?NM8 ?+/ssuvE-\ۂ¯!$GcAqTVa? > zyx-{/G̼e[Β@YmP\\^_ZxCz) @hze L< _U]kCNHt$Պxa-G&2{ClJϗՕ׽oI j~-@ DU(3y\Dmjzu}FKedbRXX rC$y"foPF }-k^߳Ɋ+O_c:GI]20XBb[H;InsKFrj2G( _l+#&_U@-%\011;/^N|.2O/yϰآqzKR8)P8q}S̹;v*UتO?IC-υ-=&r厽;Y9?I^^_OzC-pv*UثWb]v*UثWbPW5ԾIb@O䄈3#_eٖhPJ]Ȟk)Wb]v*UثWb]v*UثWb]v*UثWb]qT=1Ull`r[O*v*UثWb]J=Xo_MO_½8o_lwc_ w|[_jMr ثWb]v*UثWb]v*UثWb]v*U%ս/[OE'BߗOǯ݆/z>>IZ݊v*2cEQRO`0jyZ$MzsHЁs'V}\#E~S̑:ݷp<ȲƮSIE@iY17dk`yS^'i.kk9 ߽鹃,<ԆnzexkR/Nwl%n)H>ʨuseh_ :wNzwHGH~j},ޜqy}z6יan6ua9oKz(wVI36[ui45A-=^1?{u$3 ;d>~ly&vww 9㸀X:OREA9E,*];Y=#OFAm O5LU&<.7no $Ku^xjXƆpߤqY-(ຉO8-j6Y̷c$7*Z攖W_ U;-aW<R  #ɎX^Xֵ.5+k[?V:T(W@!Unlr#hܼSUHӬؼX!UL12Ok}=o9 Zԝ3t_dag?uA++xm,Z4i좪8|0D߈jҽܹ) i]]kVU$cqERXu >EFY|1.G@@,Kdl$݊}+y܁|\ ]?$Q F5Χ tScsٷypLԽ>#y&w:,8G$l(ѷd,gthy[N:k޼!W|6c= ITM J߮-<imm| ٛ.IHߌH!ՕW+{n0/tOKZNQ@hj?0n,lrfGDYa%((]!xfYJt_Ʊzc_!^eP"jx|,utnAGɶZv*UتIz_t.~/?\4 _EvT}v;#xs?.u]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*yߥ[ާĦN^^{R\\^juUvεثWb]v*UثWb]v*UثWb]v*U)Ԅߧt~oNHHՙ(*>?'7x9.D}#^w˚mN]K<#f:!~s'J=|Gw~I145U &͔<ߧyWLPn.aK3p#UR7o|UZ5ݼ#mti]JkKV;zgJTc-g薐}T^uѧna,L"1ԲSxF_̝Aykr}_[Wh۔.|T>ٌⲬUثWb]2Tc9%zX1T+Gx%^ nx[deC|3+7=E&"'X"K\'maIġ2 qWbPF#bQ2tl1(ȃayP|J{3~Kq;8XBff; I)eS )o#Z㺻ZiT[D0n2?M@&Ot(X;exqGISM5/)G<d#l?ww܏ع22ĩi1Y%vku-!Y1ʖ$ Ui|9-x,r[$ =ymI?%k{"8'o.f-mrw+'X+#Tn)]!vm}&E p̩B,@R~M(UتW}}PݚK|#E"#"g_*/Q +uY.Ԟ'-Pl9ԭzeaDrW-#Y6J"h2,YߋiU]RI$,Ԑ*Gդ wHuf`YSJNיZp9W??WKXnGem3Q{O"mt_0ygԞʺECap6~i\띊v*U(DߤLM-zV2SodmZ]S=s%Du#MثUeoSRXJS`ֿkGݭR_/-EK P**扴HdEKXcË8Vi\U6]v*UثWbd#AΟ + OE^UrvO2D - SPڞko-<)'Xaʂ^D *xXQeY(jWzbWn<>#WĂ(_W$o*1Wb]v*UثWb^iS0qKZh#BC5P }/c^Oך]wY;IijFlU]v*UثWb]v*UثWb]v*UثWb]J=/zXo[x>>S2WMsst>Kk`}Rk8N]v*UثWb]v*UثWb]v*UثWb&4~[Kԙщ~ v\e38]kQ}_yʹysv*U }YގPYڝhSy$DIBjux"70P<| )P$z1G2 bU~k&>ZK6 -9m̚ȼO;}W`;J$60SȞ ~/~F=_{E{gqKnW}Y!Q_rgzWllrwfH N7vMǮV"D6%8 Ԛ1Wb]v*UثWb]/8_.^mqi=@h" WTGzbX퍵xekp! 4̭YxUhYӿ25iJJXԳ/!M , l?0 T:e%kI Aji4(6  ]K82PzS] CC-R74,>3Xj5@#20.ˠaJ<]"O&Yism(RJ O94M+U˨%ZL.`I%+;41WMvm=f3\;n UTY CitBZKޡW&"?4rS"g<"d:ONKO0]E $*UjB 4,UثVT*{z!  e{u7yYԏf(*ɨ^BQQzhPX B\='冏c}/N"< HsǒdyER[7w` m.Qx#W⨯yqaHȏLE,Ĺ f>]o%̚Ek&̵=3azcyCZז5{y"*p9&DWc2)aI-M6ҼQ1dUYVğ1DFŁj^JeŬDq/Bi&H*cdey'<@km$S$Yڊn) NCW^saf}" {Y =*B8hWc˿7b4yw2~+˒Z5Ĩ%y`xXcBO\LnP!.j@ɦHY;o, 1dw糷ykQq$\UjB1#oMi8őZ]Zwk*mp,3!8،UWv*i>kfJz"+C}U_NvU\4~/x7\b]HCz4?/EDej~mM{qxYkQ}C?H.u]WZ3G0dbg.:w+MԼMUjR5K nn9𬌑W׶*|>}B+MwT]'\;H[4*SOLK-$Ȳ[cӧX.˿:tx%̷FwUD)zJƼyTg$o8y;OG-KS.n~B-qFR:Q>dZǕ55G76jrncs ;u.8X]vYoc,M2[i3:s zAMVq8kO4ZMFZސ<01cȏ*խdX.JusP%NbsX0t wSmݳ^7w2JeL!f )lUW.{y?tYän-+λO,[[˺}嵦ζS4^;C]s[[nʐF*9yG_TgkWL2\,et"Sȿ':T.I3sM$)D(>nڦ ԍ3ۉx#WmAqTWEhIUS,K#_e b'K?0<=ϛ5BJ/-& -㍽S$JC!g4P=VU5-K@0-FmVȗk/1XD~_*b;97w>mIZ(!ONdE ۯ8!kFmMttn^i5͢[Vfnzb?C]򿕼mbXbwZS_[.ߗZHmmrl/(h48~f?0fG/ΛLb~z*UثWb]v*UثWb]v*UثWb>_@~}m^9N^pө}(\^Zt@Poi\]v*UثWb]v*UثWb]v*UثWbRG4[[Ҋ7֑8<:W+7oVH<r>wˢk8JwzVS3s(+VO?izƳ9nKRҥ\گ5Ӯm+ :SOsiP^˧<w2#Ft4Kʒ|;|ǴmHKw'?3Yy\l!Yk\Y!f[YrZw$enJuOR`cݎ]TICgX2Dgd`[ĭP%2{zx]*ͬdӧℨpS3+P!K!y[6fF 8;i^2O^S4N (|>MЊZjEZìYbU,mDilyF))a0~\}]p/f$K}H}69sAe=bk2M^h)QU;ߒ ' >Ce)m?4c˼KS}Tp[ i)Yzc=q8󏿻eɧDGYOBb4NSZдpx(G-GͤVZ- $b7 ,h|]ӗxNG[y CesLi'@]b2VV6Dۢ (((*U%т~xύ@܏9a~U_nU~.|\_?:]{Wb]:?H8}aoF(䏏3Qi72ݏ{_ d}5Z;v*!yg_,eI]>ck_zO 3Ic+hp~KYuɯڣ~{_5?Io1i]U/::I7It\'¤:U<͟.y^W4Val W'@݊]v/᧙54Zܔܘ׀ejUcX^j@%-qyu]m}eUZ$ytKHAm3S{K]6;i]GQ6}ܷ"56YgLx,WѲߴ: ?Q./IuۄwHബn 8;k^hDOPХtm濻ż bG*.?&|0Z˥\kJ(ʓK@w}UNw|i-_ ;+9{avP~{c- ~g<ٮu B"iQVf^N*y5Dҵ9,5 ɚaG^w2: V@Ayg_`,e7c=H$E? ث~Z׵2Ki+c1'9|+Q\UWrC˚瘿*u /CP$xTYbjڽ֥qbCkBTV_6jG[Qϥk>\f Q[@X'2U'>xhC+Uk8Ao?\:SeWlp/,L_y|Mm$sNMS*y>c׭o&i#jڻswX3mO|U+޻&RUEƝ4 M]yo^r'̾`Tn[k{{+FYרqV&|hcŸ,eTץ&򤉾k8wA쥰}Ru`e*Ne֏YL[9&HGxI1TZǟ?-t'QסҞHgEHݝ TYי[?v]RIycwVLޟ#pتƑ[5Kw-l.-tnDч'-u/j/<jyf*ȷѷʊ̏ȏzbaRV@q?jb9Lf8!]v*UثWb]v*UثWb]v*U)~KG~Xo[њ87^~Tǽy/vI>>z&kUثWb]v*UثWb]v*UثWb]v*V>jz>ȳr9z2~.M|^+#yW<˝sP*l,/zv}(\^ZtPoi\]v*UثWb]v*UثZyZخZ " Zׅ:֑7Iӕ̢ĄPrjE]v*UثWb]v*UثWb]v*Uy<,kw{+5ӑ-8v*UثWb]v*UثWb]v*UثWb~}OC֟WN MOmSv:./ -q}@sCޞeιثWb]v*UثWb]v*UثWb]v*U+~oI#plW98|~5rM2 ثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*.a3):+ܑG=ߔmx,3Fmv'zV^_<9 "S˺c-ޑk&b]S`a#)q1[/NN{h !W#Igo{by}^N-ʔFK[jxH:s?qW<~7.3I*^` d|aWG>.(}F?\z weo-}^5/ǔܩN 6Va~B|7pc/x7RXzo0Or8גzqwL9}q#<Sծ n!ե9>0>u|P4>#N, bOm->-ivPRi݃{qӽlC=4Y+kʆJZZVUigaqӹ>_/oVH׻SKc?>0=:w:·?wG5X^./y߷~ø܏:C|[i,ו-jv;N?C?;%̔qqJuoXøܟqCG?zկ*eVgO\|Qztc:(r?#E?me ?Zq&;ag;(sBu=:lG|xm}^^<#RlN/ɇ'wRu~_} nxRn\aeƼWx¹?pC_˼;+,Z9) l. \>/t50_p],^+%~\u~_~M˄zJxט;~U6&OQ]ǩ[KgW'ۗFnT+tca u/u}V~/.7/Ӎy)תw{?qC=O%Ck!1|j֟env|Qza:(rCU͖1'ohcUn()O=qӽlC=4Y+kʇJZZVUigcקr?W!|_ޭ5Xկw?>ov'||aztOt!>jFGʏdǧN?)2VyYyq~ ^LwEq6w\P>WKg?Woqʔgnv8|Qa 锾&}èG__B[?Tdx2wUFl0g>.(}B?\zwe%~{_XחHPܩNl[;aE!>+e}ÝniV/}YRn|_H5+Nwtyw6%ϋǺ^|dG?W?N_W3˕)n}+K[M_}|o}RՅMσKqƾw׎2>86%ϋǺD,kpR?Bvx~}_S_?.uOK?W&Y= xט;~U6&OQ]ǩ[KgC|[ryAʔenv|QuG u/u}Vˍjxגzq6&N>qy*3Yz/]A_KǕssZS 1aGqӹ'WQ?P#C?ty$ v֗m)?gw;&><qErV{եl'5GuǯN'ίC|Zk"VZ/~}߱Nøޟ:C9|b+yֿ_}oqӹt?zu|P#OSz&_qO=>/.6)^LwEq6w\P>WKg?Wop*S)E0n_P_>rQW}Ж&=&^+e}ÝniV/}YRn|_H5+Nwtyw6&OǺ^|dG?W?N_W3˕)n}+K[jxO;ηC4}c>.Rn| W#Igo{by}^N?T*SN/]oϹ3}<_PkݺOK?W&Y= xט;~U6&OQ]ǩ[KgC|y}^N( \>/x7@Ihem,j+X)cuQ:?xC 3␠{*:aN9cG_OL2CWb]v*UثWb]v*UثWb]v*UتG}[KzVuzp:}}oθ˫~_-qW~ךy:b]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWbT-mnP%)2P(`*" "h> Wb]v*UثWb6Gr%]#}T_W8wrNrثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWbRG?O>g#ÿ߮\sw8|~5rM2 ثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]IkzepXxXW{9T>~Ź<\Kךq]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*Vjz>Hr9z 7g\q鸿/tG]OueιثWbbط*ǐqUK1<ҰHRU$@*[DM!j|HS UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*hK<_@Sԅ :C|/c)s/ιثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWbRG4On=oJHZ6zr r_ jy;5'bZo~X__ɿ:yTj Ը)*5?0{KXR{-/P`h?z~_ bc/K.h+1s6jg[XVOZBU2i~x|YMxtIY{ar@h z'd׬-Uvi#ETWe_~Xo>]nʧN.Rb8K^ctM+Srkӡe0iňۖثZvgRӏMtx[7I+/?Gˮ*~_fogLs=&?BCZ #$hhAXS3Sյ2OmOs'x.@VU$T#|}z?‘}x(帎vY殅w--ngIuMKGbna^,TM?lU =DykM52$iD"fFS;"%Gj⨯!~k{\VzO4D.Bh-X27b^+Ǘ_t8={ǞZ^1g*~_~mh~rVF{jqz7 ,84~n:?z^Ƴ^Xi1,VVGh v*V%+?VEhڄ~ݻJ*ف#dWV\Ȱ@,9⨈931=yX%MJzry "tSF|BCv㊲9~hWʚUy.h}fkz1lz04늤z7瞍q =KLWb%FuPۮ*y_ʞGԴ/0<&Աݪa[~ETk:Z^?HI`8 PU(:uثѣWνkI$`ZcE9bnzսݴ7V,Ӣ y+JGPA*v*UثWb]v*UثWb]v*UثWb]:OgYz~>E=!_JU[*\MxXHϨ>iZv*UثWb]v*UثWb]v*UثWb]v*UثWbR=[V5j*0#17 [lU# "~'wEZ +ectpػO6hwvq%r!qq$SnYEv*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]h<V^ 7C*mg\q7z.!^U˪w:bZo~X/O"y_5o/ 1KӬcPw▯n</yȗ647\ޤRU>XS$g5G[]̋Ɉx!O$K=UkmWY[dP $bMok^^Gk2\Wo^qjWbWFߘKI`jvOp@-I#^ UGusiɧo,9GBU9 K/mI@_LʂOk튲˱~xӏAzo*}]ʿ/-l]T$bӯNتjߖb:~: ޼+8$MI^8phv+~O] "k1vzOƸ?k˗DImԬv!LG?ث;וyz^O%ܨ*a@I4aUثWb]v*UثWb]v*UثWb]v*U#>_WփIk-=h7;8NWa*U ̹;v*UثWb]v*UثWb]v*UثWb]v*UثWbRۯ.hwWr\Y%,ȶV!ӊ4y/~]Kvɥi RL!{0>5YZeC|s*/ʏ#. [2xҨj7gI;<v*UثWb]v*UثWb]v*UثWb]@_7yrG{v? a/.$HA˅7*~_~vlWх] k(iD#{*UثWb]v*UثWb]v*UثWb]v*UثWb]ZwGe :Gޤ-Ow9\y+u~$.Q|\v*UTSb_W4 4]2y-亚*_>AAMYݲ]ZMm!!'r:੧ߊ?F<;?-iMqgdd)5S!25x^ኡqyJ-r+9%_'ԯR({B늱h?!-/+y]ޓp),n#6񳚷ꣴu8%H__Oc}\_n/̲ڞث mZvjmVd)b!w`zf`|jTɪEL4NG|U˾IM4uH&[ wRږBJ)oMC34c}Jf*U$zc޸/^:'i̿W21'Փ`(mԜUum{礞sX&%+e~J8xR?3KiF>WPGwʱʨutbX,WךTܪ /m嫛ۍwU׵ X.=PDY%7ťm *,<8mt{hJW Yn jzg忎*|K_5e޾w.a @CʫE5zbf%y_yQO-/?8Qy~}qT̟N-y̓gEDr ޠ*Nvuh^]iױnmߣ#|#pqWZCejekcӊ$ޟ‡zfA鶺}v$&I ơAwbYrz⨜UثWb]v*UثWb]v*UثWb]v*U*ҾcX>z>qT}OA__m Ѻ$ʺ&cUثWb]v*UثWb]q4Ҵ튾t,|G$徥eindɩ 9=Zxߑ?#<{IY麫\n$KD+^X1Wb]v*UثWb]v*DJ-㺴J*6+j8uW YϠ}os'?G9SmNx1 <7!w^j-[UoGg֛U:ߋyww_/g?W>';S7Mx1(fὸDy@QyoWz^V}iOV5:ש!UMʺ..-Gʿ]}S<{L3u?K@,X۵K]9jRh}ݩ?;}=:}\1!Tw'hT h^v՗D /^z(檽C#r U3 IV6;`!,u|[e<*=;j[CW׆뗩/Q9Sdڝ|> nsp&<)=;?^[ޏ%Zofu:׮U߈KyCr_D~}o%/ROV*lSӒcwmxonC7PkVz?W6|}ii}b_zUқ?\\[qr:+Og>~ԓONTSr^nC7 }7ך'_V[%ם~d|UWJlVqqqo<뇻>@X{^KNT6O%3p"< ltUB+^>'םv}]GF\BNW>5/R_n#jrěS_nۆ19Dޣ !zb-Mݫש\;{r..M 2]n''՗˵1/^ݻScC ǧOwDb?7,g&_ʙtt\|,mڥV_z)q_>w͏7OC_6_?~޸19'O?ӯ_ l";S=o5S\< v> {HRU?7˦3n.b#՗^7)v>{_ʙ}=:}U?š\m篫/N_> ~ﱏjڤ9S7.~Ί_.z&aޞ?2ם~&޽Gl;{GEGwV h~sr$?J&*lS<7 !FNWIi֛]kλ0x]GB\ ;'~s}a/9z}~9Sdڝ>;kP{pӿ վV~|}ii}b_zUқ?\\[qr:+Og>~ԓONTSr^nC7 }7PkVz?W[>>ܬZ޽~ Mڎ..-Gpw|'~s}a9z}$~59Stڝ>;kP{pӿ V}8sk^uS#B?u\\[r9 =;\yz{q+S>$ڝl<7!&Ng=G`7VB_S޹߀.Q!RнS/2NO/icN_v?G5UQ(NoU1.bٸbɹ@>쟿q!re(ӯqXnE\V_z)9_>w͏~\_?Ͱ_?~޸9'O?ӯ_ l"G~ژy7O-7/C[?!H> {HRtttX|ĥDz8~wS=XQO:GӴ'/NKLLܙz(#OODP2Q'6&P|Mq݊v*UثWb]v*UثWb^#9vOh9GeZɱ\UثWb]v*UثWb]K4s}dO7 &fNqwd1{$Y$ :F;qVp Pᗟ^u5 OGm-b 9_NHDE9XWyu%+ }ZF`ޣc22 VHNG.5{k-K˟T3$H +̴Gblv*UثWb]v*UثWb]v*Uثɿ'];BQy-ɩ\U~VY^~]`{[?LnQh+ʟ~_un^7NwQ ]˷NAPzUثWb]v*UثWb]v*UثWbR|ãE#F ?g | `0D. fE']`~UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*U>~SkYOt/m'V⁍qVg?eyc[[; 2'JH#VVxUߕl/Կ6R:|%9"r zUثWb]v*UثWb^{g7ld)qk3jt<ի%ENË7Jb o[v_y~4q=y'6[ljL |km<6ۿ[猧I‚nɎ/~nЬ܇i/o[Q?rgS!}߯ōDX)eTJu5V +v*UثWb]v*UثWb]v*UثWbw0%ż?ؙ6 U_ٿ'˖ͦ[_ )6lUޟhvj$]-O*v*Uث?4?"sUh-~sK*S]xTӎ$sz-)⯲|}j[[}nsYe/7>&ev*UāJ& YD  X#XmHXWuuXL*9TOelgǛ-]wAF`xxnVMӮRѮmY J5 @dF1ܨ-^TkN{ۉY IS6)mg|`DfYyNqyL%I-gVO ңpv2,(?/-~o=q-k'jhrPݜZ_}坕kY&k[[\Ȇkb UH\ܱ#V$ͧ]yoMⳆ)}7ӈk^;.g܃_o4y{}=]Mku7ތ Ruԑk}2UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*Ul"sTJӑa^_6`h~jǵ~ZKmJ+/5돫G%LѥMvN4RIbSNxWb]v*UثWbXhѼou8n綥@vB>atn/[Ooo;FAn(er6mRiF;x,X ,k4PN/0G䗐>hap&dj .Xƻ1p3Ji}o6A#H-xh՗Np7s 0]p]c-(ld" za1H`<_Okne/<3ST"PUkO1Wb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UتUw5ڕQxV?Ë'1;ثWb]v*UثWb]v*UثWb]v*UثWb]v*UثVC)Sс~*}+jQP/$RI'G־*~B?&hMMsznHT,k@QԮ*e.O4B돨.2Uiz*7c.oAZKvrjTb~aq[uUy*TW-+ۡ]z>%\Gp$ =7:/!8a&5eaU Ȱa'[}D7KO}H8r~UR@tZ-eIcw~_ncMg2ᯨ#7(@~ud;myG JYd#CTNjרPEoa~l1q81;v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]Sq"h1T5\J"zBF91#7b]v*}w<޾H ;SoIIkX*Ky5x>ZW G6R( EWb]v*UثWb]v*UثWb]v*UثWb4t[(aMf;v*UثWb]YҖOM M7mҜa(v*UثWbTn/-iqMbhܞت}GSKw+faO6J5{UM("Фf')_v$N2yqt vTb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]`t<ӪϩIkzSFidNwmAmRIggcVwc3NV#~Yh:qys=؊Y@Ǒ-nv*f.^ۙc m*⇗ r nC$@lsZ򯒼 bf:&9cF# O5{es NY^h9]2k[ZM9 vRjҙ)aYIw` u ZCiO}*XtUSXl}!OEp|~foդ).5$S%nga-)q*~ω3eC#z橨y˚uܖڄVEʎ~}jǠTa2H COx$Ջ2g, w oa6xxkncQC1W#8p!i;x&RȲ*V(C˱A~*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWbX'?u.M{e\eR>exЍWkMmoiz 패YR6hKzn߈%55-=PNˁp>3՗]H-dĦ𮉪X^iIi:__j]eX ¥䗓ws/k v*Uثk^IꖺmBB'9Uߛ>dI\Xqqk]Zw 15]M~ { o|X귣Kn`e(mi&L[MPv9Hg)}NV]5^z  f&AL+(xm!z*UثWb]Mc(WuS+AS#pF*UثWb]v*UثWb]KȚQ]UXu!1V؎T*5tyVѭ_.4qi+g1{o-DH\y5885Kͺy}$9HBe"dfOrSE鿚na-\.oy@Ј~_\+Mv<3UثWb]o[>m[^Zo7F&Vt)@5L96~by[FT3G k#E&e3/G/|yKvjP1(T)S\(EIb]II󝝷o\GhaWOX¶yѬi)+o X4y[ M5 0ڸvkYny(( H(V*Sv*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*{x.!hn#YqGE {PqTM.FĴ{D1[~ٖ3FbrE$P\}qFV\z$%56Q};?ߖĺc6+ߋ\c/o=zee쏪>Qvz|On,`b?~;I-i-*cgmdMV[Wƈo^RJ}2Sw˄Ù܀mR]و:YEO ԉ#p!.@V^&\@Ȅ閉?娅]i 7"U=P)"m'w@d'f[o)>YMLW3̦g21PGA9]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UتOyGA׮-5;s4][)^"۶*<;+KQ4fY#2X!VD^w|$6pWJm%hn$T<6 2-ɨP 䧐}M>XLᵚ)4Y9#r0FvWbRk˺n֝m[pē"НV;Vy>+T4Jξֱ(ւt ?]u oMN37,s@xޞvsU1lKeyg˱k-ŦZ6(8J ufv*ͱRM:*R_@r Jԯf*]KJ?3Ao3]G坵xaH~$m鯧Swz'Zݥ֓ai=vt-MY3TYԼ xK/mozֺ]WKm乸;/L=.I(W:쵦* y2yu5+7"i;3?(cuREĬ#]EA]v*UثWb]v*U">X{eoo֛PAH=yOƔ.܈c ѴѴ?.)lt69U VS 2FiE*2ŵNdC,I)awyoʷs}+b,V* V_ǶJ2475=CkU66>e_8?gvdpp?rl`DaIy?f9VLҟ>]Ѥۂft>TH'*JGc-ɬ*`x^Ge2;O>}ŏ$)c5&j=9(h]]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثК-FOѤ{I $zT6ӓr6՜y$VZZI$SeܵZc!V+=^X7EF g j1E~  ^ms?֊ b5KzI(u1ka4nt+͵ڴE'eZ 1$v `j/ɻNJ.徿gY eӼo*2*1Wb.' .'q0I,UQV'*-2oo7oqNsoqHn vR9Sř' j_P{(Y~rRVHo7ZX\Kq[8hS4L5F(iPO1uàE8ƳO~.X& v*UثWb]v*U[UUثWb]v*UثWb]v*UثWb]v*ӎ+5Ry<%ƲL$LrRiG!lsJ"'Kbygy.((_O6$HdAb&a'?ȧeO,i:-5=Ll/`$6N3+ٖ-͗`IꟖߘm좵h5MJ{tæ_Fލģ<[îN\ReGVX̷_k1y24:/諘tWCҕ'ᯡ?͑#<$*眼BK 2Y[ټoI;A,v*Uą@7$K:IRYS䲠CSET튄yBR2YV1VM:er?//$VP]('dw#Rb]v*UثWb]v*UثWb]v*W@ (|1W7ֺN֡^iP e)C*}o$4\)f9(ek[QjrZZ\i& B){q~AY2NC9)&ޡtN4//d !YE;V2Ge sRK6² t2wGWZ^EѵK0TxUԆ5[S%]v*UثWb]v*U'Xh+vzU[rvW׋qGcȦVw5ǯVJثWb]oë$/dz ܑ,kCߧ( e#nُ),Ham\ih}:%XY )bJy:Ȫsoiw[˅y}+3߂ Uv*UثGO3Ƥx\@1DPǝ@1u X%|!qR s،U /˺XịOFA*I$jɠiᒈ4BѴ+YܾhIM]=?5{'h€meIv*UثWb]v*UتY1XsA/Wֹq 3PylUgɚ~.Wp-soQB<s~iyYt2j_ޘvloƲ  bgvLf֗swnڅEnKF::` ?]]^d<-x%>LREX`AF]?Q=nDYkˡiQ@ @Q*G֗>YC^>DԲ&rY3<LA t(1TPUQEv*ǼK̞Sl/ WDjh*mWjڞz "u5u u.b[)΅xZrqۊ6P~cO'WԵ #Tӣ[In#Ʈjsda$x0t_'S.[+TJ\hY$9J pޏv*UثWb]y-澼z̚uk&Xnf2DW@?ydҗM:e棢X2B0n7p=V]R[L#M2I_XO%bw2DPҹ1DX-+ZyKMuKt.&N@Ȅp񧨜_nȘYv*symkzq{VnlU[v*UثWb]v*UثWb]v*Uت$4/#EL>ӿAj>iC_sMmc˔FdjTd34J[\?Oі0p#>~yr#rѬl̪eou1%?A6j%1\9$tMO^S*xLRYMq@F 1orHr- 5l9[a$K@p'Q/ПW̢. J4DjVĞ^+'{`oogymyn$v#|R栫dUP=3q^<2" tE hFA\UثWb]v*UثWb]v*UثEA؃5no[yKyH#1X! ;$7-i 5p" Aڧ2Gg5$2O?XXnxE[RBJH`w;AWcdݘ2 uOX]VYD zK6'2ӖcegA((-QN;y`O] BzķWZۓNNY*UثWb]v*UثWb]v*_ƁTVD=CE劼X$PiR@{Rf7k^>(䝶2QTZ լYjPsU"yW fVn}?Vҵi|i(:qyR㐞 Q":Pls {i DaH䄚f'튡5mmѵ zEdiFe V}9Nݎ+ːFGH-WZs{v>!#]xN>W?k: ,Y&?Y<|ǖ29t=߱?QՀT6tq]{e(?ڐm%تl w-Xw?=WwΩ%OL0` jP'yc,k,Oԩ*JSb7+K< ] 跛 ad%aIKN.<$qQ2w t3Yۢi^iW&(ė#ui,5%s7]N~i~x5Y ,!,<ؑilė2ϙgZ]C^;]F<i])*UثWb]v*UثWb]v*UثWbS^Vusq\G J]frN*)y#VxyI_.MsZM4LН=nfqr;|4StySpZG{sX9 ܽ}ew~.*+* /uO˟/bЛOjKI,ml8oQ BԌ)OYiZ,u=>[ 5m#e2qNa7\lR UثWb]c^a][^]M䶵 %zxx^_MIGX(os?$rISuQo<.t{KdOC[P[$(#HdպTcfhsA,5 6k e Fvҥ +JqyֱNϺ>M%xYX/!A-0۸mDf!?9RiݖV+^8 ^;)ŔSfmr/K5^P4Z徟I,sH}^ uQSd&GH3\%κЇ8$?*ƽ\Zsv*UثWb]K}f1YlnPxf>3#L}|'I!8 PEKxثWb\HhU(if Kvhti%gx~90wwwǚ59&ON! 8F1e##g%k{k{tk֤(OWb]v*UثWb]v*UثWbPڅVPz »z*#3_Ttcw!r7XӨ=s͔}e@YfK_U8PSx,?v }xï˟i YxZPJ;}:8c4z"G务 ݤ~#` @jkԍF] H\OdI~soTwVo_wÓ (rUثVEX*N۝*mHY$GRcTIJ1'(˒ Z^$X1(jጢG5 yr,]v*UثWb]Rk{ ӒԎ1TycD`Ubey.3ėzfTQT V ^usYHK-|h3#iCPAVGjRx)iat"_Q^+ ʹf<q4gx#w6PZ*FҿKu .S? 9:8?Σ%n2qf=1#&OWq=3a0{ 2c3iF?Y9D#!8SdB(QAJVI=RuX,!VmcG?vf{z!\NIg/ci&6ޯĵ=G/9}I2  UثWb]v*UثWb]v*UثWb]v*Ӣ:pEA#@# P]HYEAk1jZb,MI'@ɡBeӥ{ NEC?C#RNCϟϛ7w^_oΥb6G^I$I/ה_-d>mﭒMemme PQ{̧߼(@ (ZFGKq#@Vn }B<)m3^I'68P6=9¸?v*UثWb&)xePH]Bd#cLMk+u{Fx:B[5OQDy.RUN&=ĐHQz.]v*UثWbn Vӯu+( %sO|UF*?Ymu;#jY?J2#iᒌ6BF&_m uy5ЬP]d u),]ԐY@o=۷[]&LңKC;>%bb]v*UثWbZ~8PJw KjQ`H4Vr"vS 7˵Ǫsȋ$lUYMA#)JUث0cC"V,Z1>8I ([1TVd7kjtrOwFV8\G# _MWCO*7WچQ\ Yh-jz ,}}4lUUB@` KWb]v*UثWb]v*UثWb]Jtrr !z'˹—rS /̯aK}/=MG B*z@HimDxz5+*]kk;י3} sE_Yyi-UaSʱd0R.m8B6${7%Nܠ2v*U??\֗EO)Un.uZC$c(!^i-N)Yf*y];&qפ =&I.umC]n-oA8g3rv)7,n]V)$гv <,ۍ .Cq(Iv(V|:]v*UثWb]v*vuRsmx[1HJ7#WJ)튰z֖qq+[BF޸7Yd! .RQ͇!*oNkJ+VHGUP=(7'QzZ^6,_'*v cN@SAI7kj]5v| NQ$ & [qn۰nūXcvaRi^qj.q;5Q^l>Y,5gF A5nG]MHĠjsCQ KJ˥մWa ?AH|>ß-z~Yw"[PGiߎl>5{{m}?'noM> N:w,s4E3b Fy7c{G>֤+iL6egkٿUd3g3۔G BTnlZxhF SւQY%cEI$#1Wb]v*UثWb]v*UثWb]v*UثWb^) yחz-fԢF.-$k6q#T*j)41jK=к/OvfL=^&qT//ihq]Qܨ_QKGy y/J5',njYǑ<:a}u Zj[F䕫#O-UB2R^]v*UثTa%)%oRCӗuo\lrDMy ]6;ETԤ7IfF#Bh.RjӬVsr!&3+YzGbyتS/E/֞ )=)&Bq XHӬuĽԵ}E[1Zڅ)qġ#?P7wBTY+{vZZާg I YPаPrLW{+]&/$]fiuK5mHBdbJ 3q !ثWb]v*UثWb]v*UثWb]`_ߙ4Oɠ5Mb}^+ŜI8K@ =F*/1y͡Ϩka2^kLK崑HŽ䰴WU-/0Fث"֡9]jU栺ehn-Ŭ kvӂ4w2 b;NcѵvԼqo ;X!4WorLQR1Vu^_GUׅW2ݭFRGv`k0--y㉤ʥ79BXFIUY"iu2"*b ϘZ++Zk6ڽm_V'YeMsW@6ZSq;BOb{}":jW6B.=( V9u)]~lyt"S5զ:fAg*&r56U4`jǥ2sRP3zicW,?Eʶ69fBFy!lR;)-/-&_ AßFi++_ɍ}ڬV;&*OH(Y}A]\\;?_qphs-p"NO)- 9UثWb]v*UثWb]v*UثWb]v*UثT5ΙarЫIJz4U ҆%3T zKKs6@RiD&3o_l=sw_ƫ*U- Z8ȟGql. C~q=G$RUثWb]wߤ㟊j*:)ex{OLNۧ*7FN$I4rqTAhX|WD+?E~lD?>ެbf+'b]v*UثWb]v*UثWb]v*UثWb]ZFB@%M)Qኡ6ŬRȸFE 9ߘf !/YRId=WD<)'R2 y @(]&8ZDe+ԍQ*J.85$ *(WbTJ4F*Y5{&=m?@~ 1UثWb]v*UثWb]v*UثWb]BN;x@.;PI$N*?]i9]ӟ'@S4I7QX/l}oP]S_LXoZ:NȞykȯ泆fe%f⵩GqVAژΣ!JkeK=g2AZSoh ,ێ@sGi?Z [ء>Ie&-N24}v'[{S> VSIxШ W|c kCoSViѿqLgKhONnjZ0ˡQ˿;R*i$l 7ypANT=czp$ S  )RXY#!e6QUثWb]v*UثWb]v*UثWb]v*UثWb]/[Ц@Rx3T?(rzt(!58PߢjQ/ACe roWދiRXUXn>E2ov*UثN"2:GYN$ in7'H@ B:OGLeY[ - Uoo@r:P8(244@TvP $e++Wb]v*UثWb]v*UثWb]v*UثWb]Ak7Om$d6]<%{+d>(J2OFGKWb]-6V?\cNTL>#b{JncăO1.]v*UثWb]v*UثWb]v*Uت퍥,/bqPF*G Xl[Wy ʋP J2l*6-kk{h@~L&K%sb<*t>4kF1|?ړ\UثWbXh^VlNmcb- T4ϕ}Q JZuլ-1FTT ow$dzx^U?6>}[:ڢD[d6HH@>Ojphځ6cLy5',"PuԹ])Ooz`S AcXI'*LUثWb]v*UثWb]v*UثWb]J.ӵ-z\fjWo2e{w_Uo$T. ^}CK02 v?.H[m9] p1P=Ԃ6kkKzx7g_fqj E :jV,"P"D"ocg緾XpF{Kn)NثWb]v*UثWb]v*UثWb]v*UثWb]v*UثOǃrZ@*%cz}?U:eL[hc n7#2q1Y9;ǿcU7ϖőX]F\n#t/|4Fb[_)jzE%֖W/fDެ:$Sc=+S*˞jiIx4Lm2F$T*b]G0Uyhjx̀9!]m)74_/Pnn#x yJʏECz(dMxC6{~\^_qB4{P3E<LnQ*jO)s-nl xf8_ՎC/ uSN?dZ4-WD5=jwY[LRfD]8>]v*UثWb]v*UثWb]v*UثWb]v*ӺFxǰUZsyBOYEnob+yCq3>@|dLm.R\Mwsi>V"pb5Hz듄nZN4+ܝ qcyS\;qRVOو\+3]v*yU4,Zd5JķVAkxާ CKhťɵX5#*֘n^? 2-:R}G^-w[imdh{t>pFE7LfvIXM~e֖Rivx>$Z ]== .YQVW1Fv*UثWb]v*UثWb]v*UثWb]v*Uث5g.`ҭi@ޚF)ggPˈ4ژ|-%D$(}@H9Ÿǯa#'8CnA4̾PURYyvr~pY*U.syA!MQ@KYP6JT;S1TD .kkXW֎?(IOP ( /Hb{ӝq"&80"]v*UثWb]v*UثWb]v*UJ+[in&B{f8FKȾdv[kah2$3Iq&Ldz/|z<U9d^A9 v;Tv*UثWb]v*UثWb]v*UثWb]v*UثWbHu ook<_VVmbo S)NJ1249l?/5?=Ѥ1XDV1J1\JR4DA=OQHt"yVYSFP,5+YG鄍d0OaȃaS PUm4:K{[k={[pki”( kc8}&CG4!Qt=zX[Ȥ'Z .2 .1PA*}a nbp*3P$3̟~uwص-:;JO%2F q v *\k:r pl0(E 5}jBGF*]h  <8/e=SXd_Hb~zB7BQMS ~E?0|ۯ8jZod6ZAC Zb9) %B1Ti5:4$zm; W=)X`Ff^Hu_(I{Zäw"9VUckd)(qN?N@`4db,~]Xhhu-U1!DOI+ZZE]v*Uت%$+ @yT`H"Ns_늫]v*UثWb]v*UثWb]v*UN hyG b dhnU+}VTCd5lX<{w2e1pyu?~< =r?NLxW1+Gq $ 쨠>@bWbTvJYd"Tk;<$Gco|<G{S:}sNesEg{?Jic2v*ucev.Iu OzdP7H! O֝"cE%He%y%pz9 >ǃwm<ɣ8.hkc~ct̖z͎ygq-pa*ѿun[w,Fo%o3FM9אַ"!gKYT zrw@Xӗ\U8va%hәQphAU1Wb]xImCbY?I)ěfe40^m5oҤm!(QXWb]v*UثWbZfUR@P*I1R5mNuE,'|gC;~||8_?5ibv*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثT>c|6\}V]"2y9X"(XؖbXΧ۽mrVM`u T4^@ʓrIE^;1Є~dsR WWAuoDj_MZcJIaU LUثWb]v*UثWb]v*UثMܓUa[{MTXx2 zSChnfFG y6t*#PCnSM#.@cǐ?ԀK{}J$|b<"Z_h-1o{4r $cM8U\300п'cyzF""sT"yߙU9T'fN>Uv\_ ynJ ꠁ(NX'Rƒ=x:j bjkKE `P& dIwxwoK%I,S̞9$y\&k2_1J)#(oX=5WsvPW+'Rt?# = yb]?k>q%ӛֆ) \Q Q*${W?1mP隵he>-ѿ v:0v2xًCΑi-ylch})%kDs/!̙]rr|<2^syQI! ǏO|pgu CP,u&ӯ5œߡZ1Tv*UثWb]v*UثWb]v*HbX{) `ADWܜU.%m52*u0YRgKA pyYطI/T1s/< Zmv*UتN?ܾˮ` b|3N_`gc86I_ OCoV9F?1iv*U柜Y׵-@4sj-m2(dz8A#p9͆ϒ/ʗTt[K?T^ؤRKH *'54iKOR.m-+!Iuo,'72ѧch+(/,Ŭr` B[ԐIժp+1Wb]`ߗ/\Cmy4J)J+L/<7/4S]_K3 xU6/O{۸_y{J{frf:Q͹ \JBI=GV), +SĎ.(| ܺL jfny^_\koxٸ-BW]gOo/Yɦk~]ycwIk3FIRoo$AԬ.4mGdS+,@P*qWb]v*UثWb]v*UثWbԵaӒOIt˭1%E#J~gߕڵֿNSeg2qGw,qU1va5=Cw:%i@3R_Ǡ*ɫvwwz͍#Qu4U~ly8V*qWb]v*Uتե K,MTdP7EHabiW֭u/Ԡ]$`в1H>ye'?Ls®X d- A;R#%io~u| ^~`6 u^E ב Wn*" jHu#""O$|z+.F}Д Wm: as;6Q_&T{=m"y7&?D@;'S:V z pc2CNc[ i\cE"0 ~`3ˎ]EWb]v*UثWb]v*UثWb)пou{ɲiw s ̖1ͨ"[5RΉ>4^k?;kz40h鶺 c]%Mmiq<$F93ȭHoBHSʚ7{f/fie8̮\TUj^tȟZֳw/IQ֯{$v\IkeCƃ<{*UثT,1L`Dy%T}*ԦhT澤/+Nͽ20t?5;x$Q(TQ s2$e!S"}JZ}Ϳ'A*@0φ`EtIڒ$-7p Q%ثWbP:t3I+4MňnUbi6܋r ! (@P ¡ iX ƃ(co___5Ii}n<]H!ѻO1b h.]v*qoͼ 6⌧*;1yZKM OО+HZCqln~5z^eekcgKi ((jG*UثWb]c_>i ńjWeY`Y&X+pNU4X|NYC}i{ CìK 1H#@f%"Pj@PO0%-6q;\J~$x_XUf76k=6NԼ404-Mܚ%<ŞPSMDFi8m!8_ՍD ʮ:m M`qT'0@txNUMĐD4SDaUa]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]iYJNRK{{]~8Hżr*tfV\Ȑ@HuM.]v*UثWb]v*Uت>Rxf=TTy%֠-QwX}3Ca0.O2-ŀB鑌 e.1yy6c)???A$Uy>Mq?+D%($@;9{s#~i k^Y&vU8efyfaˑSW f@+iy@[LPnthw*ZiyJ#A).Zie k ހb*UثWb]v*= [ϩiZNtoEpپ]Oѫr^U>BE>Pj~U% K[ymiLU_+^aX}i.g2uռr#2VRFKtW~Kh;GKmt\t銣,,5+BQ/])ON2QpEK?,|Z^ũ fow4RK)H.%ȪgaMKkdXY#UE ؏0OӧS2Ʒ/]^ҕ6NQ'㠃1zKBSr JX, ˋ}m)^;uoMČW?ڙZYZΕ^JRX3XZ/e44JHOn* XctT:Nڧ ;q^٬6!5o9)@^dq:|~]i֣&]oRRD{}:72 cn#^dDh&r|~j^Ҽk\j,4YBHIK'>݀@P4-i^تQ{jDL\}NXiRO!ƍd)=:'4KRIVϩet:@y 2ÅL|)ͭݭ"kYQ$Ly#aU$UX} jWb]v*UثWbR˺t4n+ A0䆪z)FY+CQexH.\6N6MYխG"]R'@ޔrd qW.9:ɖoB7jk"E!*÷"SJ;v*UثWb]v*UثL` qU{8 ӷ UEU|2x%w/CƵT=Jl/ _EZiv*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*Uثʿ5>raa{wege}̚rLNMB"6 ˣY-_uKm2.۽ %O_˙Xs]~\Bnt/^UM& [̋4i$޵Twvy9~%~y^MSV]({"S*bY"RxO\fXWb]v*UثWb]v*UثV?W\"Kx\Ff *Zt 1V)KWb]v*UثWb]Kn!IhڱM>(5/\_/짳丈\0QJI3P eyqHĨ6UثWb]v*UثWb]v*Uث<9wث|ũU󎻧>=:o-Ck%$eZ",k_ D{du/Λ|ժϭ`|mq4/#x<{2 nkRE {p,rוX2O3]yzNu[\jK"Ehw=2,UثWb]v*UثWb]v*һb]v*UثWb]v*UثWb]v*UثWb]v*UتN B2v`<  A#[;[X;x$&(OUWb]v*UثWb]v*UثTpו!{DI/#R(PĚ)8ONZŴwWA*OrW>bcv~70Ck6XDlG*zw>CM WQ$-Z#xE]]>*Y^ZY{i 4Uȡ|A*v*UثWb]v*VʯqXBTxbi54X<4vŵ,`[;8 HAM_5?*\wU, i%asFdrgr*ZmoA(ORF%Ҭ8 '"yp!ثWb]R8çG꿇0*T9=3_XMsWbRk=H?Ȁz.eipbSLdUثGoɨɨ_S\–ڊZ\olY!HD=wLU uoGo5d~Kmc4RT*1Tu_ͱZ]G{$WΞ61Uj dtE;.aHR+fv2ZS`ﵽ&vZz~$Y7vFثu3y{CJ.$TCUB~"{&e>]muC=d3= 'ޘQ@||"#ǏU%~"kLU6tu;hQieUcj.F'~lיM+}N[n°u?u'i~lgCF-d.ԯ\U2뿛_\5ZdTy-YX*ʦ/ֻom\U:Wl\y7TX V+rVIzb䯟=!6Z\~"d23O\UWO5?2mVSg-aS3F2D=qUo̟/ͺwUtҢAyլr),K Tw]\EOK:xWPM1#y İ/N[WɖwV^OЬ1][iDԪ 1Tv*UثWb]v*UBq<UoqWʛt>um`ǦOiPHJDN!ƤBOM5Xm+.t۔9(t/"H'[+lo z +ۛ9H3$^QfR9WqJ3{#}i]A$V. !VE^{ԗ4V/a?"zB[Yh h|2c HRAV%ثWb]v*UثWb]v*UثWb]czG-V='Wm!0MJxep EdW*\~b7"iVK;hoWL0n@' ߐ*;Y.N<1BGCɗZk}nJyLUF1FGAǥ1nlדG"4En/Ȯ&ܽ)؍QT=ifphfb?VIIMky.db;NeVNo#r +@⮦_w%9O]v*լZФm&~G˰e܂i}f %'I ظ%]:{EeIv*UثWb]v*UثWb]v*UثWbXwܚ~F} +m\؛A N;ogɤM[u{LѲZ>U<}N!"6)R}Z?$zZy܁a}S}#a|T6`Icjy;n.--Ȱ%8V\fo]+ѫ?DOֵq?;X $5-<}h-G3)V$K%o?<%t*i<t:ZkW2NRtB9+n6YߗVBN.Mvy߲3M zo@(|U@寗uӡo`mN[-($`Y4P/A>|}z-G^֮{Y}hzp nb.ʟOhpm 5-6 FQ(|+%:~Vy3ʾWr]K;{-1khLQ(xnYNrNo-.u谼 s t9Xۈ!6M7Z淔|˦c,Mg{)RdX6So/T_9*~[yCefwQzFOEJFb**yBOߙ4",OA{X@p"sX֊ ~󊽃Z/ˋkh0΋*pFxw$~8/l-c47j$AJSǯ%jo;YQռ%#II&pC<@1T ̏%頧[ `I-$h h7-jDi`;kT:=וF*+)/'Kj|7W2ƦIPJS j UM%םm$k)sV!!*9lUFObl"ʌ7`D7W"vRZc;' t銰}gPsrCq6r$fuE;>Y bm$1 [k7ZHٖU􅽽oCJ(P6TP1ULUثWb]xc3d?wVh7.[,Q#ʁ劰_+k_ʋ{+q[aTߖw%)32i^n~s/튢 T4I{ACJT?mF=Gah:=(\ԜVQU;hG~Z/'KvY1OV\U1 qWii=KN_י44j:1c=ԑƭlU,Y?< HX51F"-\⩇ϒ(4CI/u$7Ȓ<)4""* KDg&tBԬtK΁J}bG*//۟MKѭSQӠh/5K+J&ت qV¤T@XՈYi^Êv*UتUe̱;G,v7/Hee UyHV>`gQj2I$sȈ}&V*+O_>y̟iZu5=6]F/`Vo*cGW$eG0)݈wG鿛is|M0 .YMJJq2%{@s0ѥS]UO#|xYZAwn#Ya}$u UWv*UثWb]v*UثWb]v*UknI/7[E{2,6aHaH׭6PC+7şEz Қl"V4SfDqs75k>R o./i.`eG߇kdbOJ2FXާ{7]\f?8?/JloӬ`}UMN1yKW:BL]~b`[%cD*U$ d?WodNX7vv+3\[ gno| JP$[g"l~y򍴏l\״#8 4TROو=/v*UثT-P+ǂO7f>Lˏ19{?E6FN]v*UثWb]v*UثWb]v*UثWb\_gymM|JH ƾdrH64d\G<$k6Tuu Pe٫4ӵN1&j>K<&ߑ&yG[`銦xЮu&zΧcqi ׂѲ)n TLUq,yCwZGo4̃r|*'ɞd5ˋ2]^k۽XY`IMb容RuuO7jpQ vCz0XXRUJ{ej^s%i g,QT3H*巙|ͥy>]lW  U?;.5k3]hV:4<ŖNJ9Q C|"SkKm?9u-#tffqxy U %5ͼQD_E7Z'ue\h˦%UrS/*B X/-`$&F'W~?V/C*<};9SF|$٬X`dPƻ1ޥ~uo2\2HcNG _,7qj1-м@@oH}h2zT~Y6fb$8?XN|Oyg>N{ȧSR67%T^Sʍt?ʹVߦ>-~W17׏:So;.]̱WN3 ~ytǖ1WyOo/]^KԭhIww]5zPSYm9bWb]v*U&Ick}rXZH6n cwAObwّqFơ#@l3MK*Q7mkRG?veuscȦثWb]v*UثWb]oy1s?L`>r zتyPDd.|.$i7|U-ռm,nX) YQMj|'P sm$XȰN=K5;v0!Sd*I4=HRi62HN~#4XP*"1VWb]v*UثWb]v*UثWb]n::SÐ $9*ZGD!܅>8jثT ƅ\jjڤ2Ap¬TȞb\U[yF˶ZK Z,5`)p)1-Uy;0i6Ȣ9&i"pVJ?/aɔyol/OGF)B@t픸*UثWb7Zm0RV߸xa!! vȏٷ3)TWrD"Qe#3h@:ȇ! >]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثTU44~-COh%f^eaة*ì?+-.m.[߫x z fI^SUNt늧5m QҌ-fˇGʕ*?.Ⱥm%K%ffUR(PG|j ,ܻ|$sCbF銱;GBW3/<oe=R~s9:P xbFO-2+ۭJW.24򚻳6*b]-JLurg4U}Hn0šm- q[0Ӳm%SA+"2HA{\[ C*iȩw4_O%yWF)*;]BXXYJE07eV06BQ{7>Oӏ?0oS6xJǚڇ Sȁ`eȌUv*UثWb]v*Uتɦ2M"B*t]OΝgfd7?kqr*UثWb]v*UتIqyo'mԛMVʼCn?`qTv*:/Lҧbo|ˢykD,k y0ET3Y/Ml->QOeyOm2E +CUv*UثWb]v*iuƣmGw6KYpcY(T#CxWb8B;TsNK:c60_y,-ngKX$uv4P1NWb]v*wk[4?N7Kԯ{EhXr czVoaɦ\Wik$ۛdP4~Mn3!2:=IZWk س|vfEFyVM*[+m:;/g =9" 1Jf3˱Wb]v*UثWb]v*UثWb]v*UثWb]Iko+_S /= Tʝ'@!ִ-;X(uhVdQPI/Ni[ XG Wj0)at $cdy暪;Y8!O[y}M֥:wZB}^-F=˟5[{{YY QRd4rq@LU6O| ']{OuŌ5 kUTg֗@Ϻ,1Η+c<1\#Ѽt PG늱1~ewxO-iyFEĚE#W1Ȧ{ftok;{g:vߡx(h'zPn,U^`כ6Y<2"YM̓J>Yy,C^?,]y_V_:?j~RTX{~do>TZC4:gE 4q7-fֳ:XՇ{q~`~eyWՓK4k}gYwQxAƈ;(cyz_4e,?1<*[XO,a!eӑyߚauюe:ܒKp.RRSTpe989?28GyMrD|'5ʷW@.f@JI%U91Uy2?0cFWMTԵa1=Я8m₌xRU1~wӭ5Yۋi]ԐHjA=Jb'̍cig;;N+I]D@6=1T.sj^A6~`غGM!m}jg<Pwb{PU?|,l,RCmqn_QeR:.˫?+>[qjL,P1ඡC5s]Ts :ϾWuJtU- eTn& .ͥ,m4F3L|r%%}qhhsztyK%+ai ~\-Zpt*Ǯ?60/4-5 +Kx$<]gvv4 ኦq/eM#t,I]Sy%|a% l5ՌӾmDK$ך'S_ʦf1$"ʤt^t֚E̋io 84XXBj߻;|qV",&y;L.jV~\:bM5;R8yBzKHrE\F[6OHj]VKoj/:di#r4߃8qV3l;MNJΧfjWP9"*_ ߷b=wVl9ȓbT?̒X46,.{=@꾬wnMH+lU`\E~\Ks"zI$*h Sܒ1USC7ޓ$2,zŽ2{PhdA"x͎˘ U24u;S^k{M"&Wi^t`c@I *qXiߓ-\`1Tr1VD8LU6bMI*،U_v*UثWb]v*UثWb]v*UثWb]v*UثV+}Oߗ4V}COime H^l@܏xot?%.|ìcZHc;If@,OjGi Ģ^Wß*9C<_󏟕FzM+R$gI]^V,dKuYy/"vg_.l/LUzM&층9KjJ'o\f'Gy`78YSmdޣ¥V'0zoLUw'?Vr{+ZWEŊc^Z w˺u̺Fr:]LAI`ؿ,|kZkW77U1Ut4'*?5UژM,r+"ܙH~Rkg41\ǧZSN,"[i0h @aP?Wr~_K|iysۑ$Qȿ"i{U]sJ'FEcܰn-_;1g>gu%yE!$ۨKYW.I|U 8_ʟ!򎏨?ziS8RC,32O4׿/?3qgjZ[YiG|LIAdGByM7튰k;*?2|=5GLԩ6 ~U;¿y7|xϗ]Wzz\\q̋HLUJѼݩ_`|m"X@M#v*UثW[_91-~-:XSa@# yb~pο:Z躄:^u[qk#*cE߉4?KySaO>*ʓXiȌU鿐&0 lU>ZWv-?^nV X,E(۱&P:*i^UѤԵHxߌ+",@zqUߛa&W_ZòqbzĿ~LUo^v󆓭_'IӧY*K]K4].£U8cg~eͬXz"T,P\BM?#uN'F_Ag|htDf!c*AnL()ZY,hvɃ'~VjKbg]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*U)o?)>,]bЬkƤ*b>-haƵ/5GNDM.)%AiTiG }hTN*X~XOהx3j_튣u$WX-i־옰D*q xgF*I-Nsnąt=T Ut-3OӬ![{+8 hR8*([%ySͶ a=2 NK2H GR $(V_>y.|cu0%,ԕM.0X%ִLu;zU~~h~e<-6w^c-EJXTo Uy'Ϟ]T׮V"!ԴU ½qW_Q6yOY`$MP+6I6Z\UYB[{+69b n)/M}T_ߙ D/K{[GNAVטqdkz|OogzKs)k@u|g 1[Y$Z֥q_^H@`A&gIK+3f5&JuS/!_b- >d7;*?(?-tqg;A.aͥVF1 b8i].-J v2@$BQЫ{q䉼c4[BeI*#6,nDrw;|U4׼yLKa4[NБЊ#Uggz/c$ffb_/kijIy&r{9a\'ّx[/3i2i_鲲< Z6 *v#LQP **UثWb]v*UثWb]v*UثWb]v*UثWbe9cxE)UA؂1V)R~Yie: mҦ9AYT|!*^G_˷]Iq0*COMBtqQfM[qD`E7|SCѠE#[%}?L_կ,/u-> .__NIQU1U־^5fu]AQ/QeQSt]{CҮ/4m'7: VcIثo\{Cw|GFn b_-{=F%2Q*\呲tm2ԞM Kff#qT^DIIt+'ףuu ޢ݇f늪ȞMJ<ţZj ^%g@zqTO|--L-XxX75XU "y7Kk+aQohhvmiJ0ĩU!*t3HӠth-W*kZ(> endobj 34 0 obj <>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 35 0 obj <>stream /GS1 gs BT /F1 1 Tf 9.9626 0 0 9.9626 107.6031 715.4644 Tm 0 0 0 rg 0 Tc 0 Tw [(nu)21.2(cl)16.7(eu)13.8(s)-229.6(\()0(K)15.3(a)0(f)17.5(f)0(m)15.7(a)0(n)-225.2(e)0(t)-222.3(a)0(l)16.7(.)0(,)-222.7(1)0(9)15.5(9)0(8)21.2(\))0(.)-225.1(N)0(u)17.3(c)0(l)16.7(e)0(a)17.7(r)-230.4(po)15.5(re)-227.2(co)19.4(mp)17.7(on)15.5(en)19.4(ts)-221.7(\(N)15.3(UP)18.1(60)15.5(,)-233.7(N)0(U)19.1(P)0(8)16.3(5)0(,)-223.1(N)0(U)13.4(P)11.4(11)15.5(6,)-223.1(NU)19.1(P1)16.3(59)15.5(\))-230.4(a)0(r)17.5(e)-235.9(l)13.5(o)0(c)13.8(a)0(t)16.7(e)0(d)-225.2(i)13.5(n)]TJ 0 -1.195 TD (T)Tj 7.4718 0 0 6.641 113.6125 701.8581 Tm (2)Tj 9.9626 0 0 9.9626 120.1889 703.5588 Tm [(be)19.4(ca)17.7(us)14.4(e)-281.4(n)0(u)21.2(c)0(l)16.7(e)0(a)17.7(r)-281.6(tr)16.5(an)13.8(sp)20(or)19.3(t)-282.4(i)0(s)-272.9(a)0(c)17.7(h)0(i)18.5(e)0(v)13.8(e)0(d)-270.8(t)0(h)18.5(r)0(o)19.3(u)0(g)15.5(h)-279.6(th)18.5(e)-281.4(n)0(u)15.5(c)0(l)16.7(e)0(a)17.7(r)-281.6(po)15.5(r)14.3(e)-287.1(\(K)21(af)17.5(fm)15.7(an)-276.5(et)-273.5(al)22.4(.,)-273.9(19)15.5(98)21.2(\).)-270.6(In)-276.6(t)13.5(h)0(i)18.5(s)-286.5(su)20(bt)18.5(re)17.5(e,)-276.1(t)13.5(h)0(e)]TJ -1.2633 -1.2007 TD [(tr)16.5(an)19.4(sc)18.3(ri)16.5(pt)18.5(io)18.5(n)-319.4(f)0(a)17.5(c)0(t)16.7(o)0(r)-310.8(P)11.4(HO)13.4(2)-319.4(f)0(u)19.3(n)0(c)13.8(t)13.5(io)18.5(ns)-315.7(i)13.5(n)-319.4(a)-321.2(c)0(o)13.8(m)12.8(bi)18.5(na)13.8(to)18.5(ri)16.5(al)-307.7(ma)15.9(nn)15.5(er)-312.6(w)12.4(i)0(t)15.7(h)-319.4(P)11.4(H)0(O)13.4(4)-319.4(an)19.4(d)-319.4(S)0(W)13.8(I)0(5)-310.8(\()0(B)14.5(h)0(o)21.2(i)0(t)15.7(e)-321.2(et)-307.7(al)16.7(.,)-308.1(20)15.5(02)21.2(\).)]TJ 1.0015 -1.2007 TD [(In)-248.2(addition)-255.2(to)-249(the)-251.5(pathwa)-9.1(y)-245.5(analysi)-9.9(s,)-247(we)-251.9(utilize)-8.6(d)-245.5(the)-251.5(gene)-251.3(on)-7.2(tology)-249.1(\(GO\))-253.9(biologi)-7.9(cal)-247.6(p)-6.5(rocess)-251.5(annot)-8.4(ations)-252.1(to)]TJ -1.0015 -1.2007 TD [(nd)-291.7(the)-297.1(specic)-298.4(biologi)-7.9(cal)-293.1(proce)-9.4(sses)-292.9(enri)-9.6(ched)-296.8(in)-288.8(thes)-8.8(e)-292.8(trees.)-298.2(In)-288(Ta)-8.8(ble)-291.4(1,)-291.4(the)-297.1(top)-295.3(three)-296.7(annotat)-8.8(ions)-291.5(for)-296.5(each)]TJ T* [(tree)-438.2(are)-440.3(tabulated)-441.6(alon)-7.6(g)-433.2(with)-439.3(their)-439.9(corrected)-447.5(p-values.)-442.8(These)-440.9(results)-438.1(show)-440.7(that)-437.2(this)-442.2(method)-439.4(effective)-12.1(ly)]TJ T* [(locate)-9.8(s)-303.6(different)-312.1(biologi)-7.9(cal)-304.5(proce)-9.4(sses)-310(into)-304.5(different)-312.1(trees.)-309.6(Instead)-316.4(of)-305.1(forcing)-309.7(all)-305.5(nodes)-308.4(to)-305.9(be)-304.9(connec)-9.9(ted)-308.4(in)-305.9(a)]TJ T* [(single)-474(networ)-9.3(k,)-473.5(this)-470.7()48.5(forest)-11.3()54.2()-475.1(represe)-10.1(ntation)-476.3(composed)-481(of)-470.1(multipl)-8.5(e)-469.2(subt)-7(rees)-476.4(is)-472.1(more)-477(useful)-473.2(for)-472.9(disti)-7.6(n-)]TJ T* [(guishing)-246.1(distin)-8.4(ct)-239.4(pathwa)-9.1(ys.)-242.1(The)-242.9(forest)-247.6(solution)-243.2(retai)-9.2(ns)-241.7(more)-243.6(enrichm)-11.5(ent)-240.2(for)-245.2(the)-240.2(expec)-9.2(ted)-240.2(biologi)-7.9(cal)-241.9(proce)-9.4(ss,)]TJ 0 -1.195 TD [(such)-438.5(as)-437(response)-440.8(to)-436.8(stress)-9(,)-432.9(cell)-438.9(cycle,)-439.1(sign)-7(aling,)-438.3(and)-436.6(transpor)-10.1(t)-430.3(\(Fig)-7(.)-432.9(S5\).)-436.3(Furt)-7(her,)-433.2(b)-6.5(y)-433.3(adding)-435.9(dir)-7(ections)]TJ 0 -1.2007 TD [(betwee)-10.9(n)-347.9(transcr)-11.1(iption)-354.3(factors)-358.2(to)-345.7(tar)-8.8(gets)-350.2(and)-356.9(enzyme)-354.9(to)-351.4(substra)-8.6(te)-353.2(interact)-10.3(ions,)-354.5(we)-348.7(are)-355(able)-356.5(to)-351.4(obtain)-353.3(mor)-7.8(e)]TJ T* [(condition-)-8.3(speci)-11.3(c)-497.6(transcrip)-9.7(tion)-498(factor)-9.2(s)-497(and)-499.2(a)-497.6(smaller)-504.8(networ)-9.3(k)-495.8(that)-499.7(still)-499.8(include)-8.7(s)-497(the)-501.9(same)-500.7(numb)-6.6(er)-500.4(of)]TJ T* [(terminals)-344.1(\(see)-339.8(Suppleme)-9.5(ntary)-334.7(Mat)-8.8(erial)-339.2(and)-334.1(Table)-340(S1\).)]TJ 1.0015 -1.2007 TD [(To)-325.7(evaluate)-331.7(this)-328.4(approach)-332.1(further,)-329.2(we)-325.9(sel)-8(ected)-330.6(terminals)-332.7(from)-323.5(d)-6.5(istinct)-326.7(biologi)-7.9(cal)-327.3(processe)-10.1(s)-326.3(assigned)-327.8(by)]TJ -1.0015 -1.2007 TD [(GO)-248.4(annot)-8.4(ations)-252.1(and)-254.5(constructe)-10.3(d)-245.5(PCSFs)-7.4(.)-250.8(A)0(s)-245.6(w)0(e)-251.9(show)-252.9(in)-249(the)-251.5(Supple)-8.3(mental)-256.2(Material,)-257.4(these)-250.3(tes)-8(ts)-244.5(reve)-8.6(aled)-254.1(that)]TJ T* [(the)-376.7(appro)-7.6(ach)-375.7(was)-379.1(able)-379.3(to)-374.2(reco)-8.6(nstruct)-380(functi)-8.2(onally)-376.1(coher)-9.4(ent)-376.7(trees)-377.5(based)-384.2(solely)-377.3(on)-377.1(the)-376.7(connec)-9.9(tivity)-379.8(of)-373.4(the)]TJ T* [(interact)-10.3(ome.)-241.3(The)-237.2(detailed)-247.4(results)-238.9(and)-243.1(the)-234.5(list)-240.1(of)-236.8(biologi)-7.9(cal)-236.2(proce)-9.4(sses)-241.7(used)-239.3(in)-237.6(this)-237.4(analysi)-9.9(s)-235.3(are)-241.1(available)-244.2(in)-237.6(the)]TJ 0 -1.195 TD [(supplem)-8.9(entary)-337.2(text,)-340.8(Table)-340(S2,)-336.9(and)-334.1(Figur)-7.8(e)-332.6(S6.)]TJ /F5 1 Tf 10.959 0 0 10.959 107.6031 488.3526 Tm [(3.3.)-496.9(The)-353(PCSF)-347.8(algorithm)-347.8(reveals)-351.6(coordinately)-352.6(acting)-346.6(receptor)-353.4(molecules)-349.9(functioning)-348.7(in)-351.9(human)]TJ 0 -1.0915 TD [(GBM)-333.7(by)-330.8(integrating)-329.2(receptome,)-332.2(interactome,)-332.8(and)-331.3(proteomics)-330.9(data)]TJ /F1 1 Tf 9.9626 0 0 9.9626 117.5811 458.4755 Tm [(Having)-263.4(dem)-7.6(onstrated)-269.5(that)-266.4(the)-262.9(PCSF)-267.2(algorithm)-267.1(can)-267.6(successf)-11.3(ully)-259(disti)-7.6(nguish)-264.6(para)-8.6(llel-worki)-11.3(ng)-257.6(path)-7.6(ways)-266(in)]TJ -1.0015 -1.2007 TD [(yeast,)-358.8(we)-360.1(used)-358.8(it)-354.2(to)-351.4(iden)-7.6(tify)-357.7(cell-surf)-11.7(ace)-354.8(recep)-11.2(tors)-356.1(associa)-10.2(ted)-354(with)-359.6(signaling)-359.6(path)-7.6(ways)-357.1(alter)-9.2(ed)-356.1(in)-351.4(dise)-8.8(ase.)]TJ T* [(Cell-su)-9.2(rface)-360.2(recepto)-9.7(rs)-351.8(are)-355(an)-356.1(intere)-10(sting)-357.7(class)-354(of)-356.3(molecu)-8.7(les)-355.2(to)-357.1(study,)-355.3(as)-357.3(they)-354.7(may)-354.7(be)-356.1(partic)-10(ularly)-355.3(easy)-360.6(to)]TJ T* [(target)-266(with)-262.9(therape)-9.7(utic)-266.4(agents.)-268.6(There)-265.2(is)-261.6(increas)-10.9(ing)-261.1(evid)-7.6(ence)-264.5(that)-266.4(some)-265.6(proteins)-267(are)-263.9()48.5(undruggab)-7.7(le,)42()-258.8(i)0(n)-260.4(othe)-7.6(r)]TJ T* [(words,)-358.4(hard)-359.6(or)-356.3(imposs)-7.6(ible)-357.5(to)-357.1(target)-362.8(with)-359.6(small)-357.3(molecu)-8.7(le-base)-10.9(d)-353.6(therapies)-362.3(becau)-9.2(se)-357.3(their)-360.2(three-)-9.2(dimensiona)-10.1(l)]TJ T* [(shape)-247.6(does)-245(not)-244.1(have)-245.6(any)-243.1(appropri)-8.9(ate)-241.9(conca)-9.2(ve)-242.3(sites)-246.8(to)-237.6(whi)-9(ch)-242.3(these)-244.7(protei)-8.2(ns)-241.7(can)-244.9(bind.)-245.2(In)-236.8(cont)-7.6(rast,)-244.5(cell-)-9.2(surface)]TJ T* [(recepto)-9.7(rs)-255.1(can)-261.9(be)-259.4(targeted)-263.7(with)-262.9(their)-257.8(natu)-7.6(ral)-259.2(ligand,)-262.6(modied)-263(forms)-262.9(of)-253.9(the)-262.9(natural)-261.1(ligand,)-262.6(or)-259.6(small)-260.5(molecu)-8.7(les)]TJ T* [(that)-334.7(inse)-8.8(rt)-330.6(into)-338.6(the)-336.9(naturally)-345.1(occurring)-341.5(binding)-340.9(pocket)-335.3(or)-339.2(antibodies)-9.3(.)]TJ ET 107.603 318.614 430.356 .45355 re f 107.603 69.676 430.356 .51022 re f 107.603 300.246 430.356 .51022 re f BT /F3 1 Tf 8.9663 0 0 8.9663 156.3023 335.7354 Tm (Table)Tj /F1 1 Tf 2.9971 0 TD (1.)Tj /F3 1 Tf 1.7514 0 TD [(Gene)-336.3(Ontology)-328.7(Enrichments)-338.9(of)-335.1(the)-333.5(Subtrees)-330.8(in)-338(the)-333.5(Prize-Collecting)]TJ 4.8497 -1.2203 TD [(Steiner)-334.1(Forest)-336.9(Illustrated)-330.5(in)-338(Figure)]TJ /F1 1 Tf 17.4386 0 TD (2)Tj /F5 1 Tf -32.4682 -2.0423 TD [(Subtree)-335.4(name)-11214.3(GO)-334.4(enrichmentbiological)-338.6(process)-11272.4(Corr)]TJ /F1 1 Tf 44.9369 0 TD (p-value)Tj -44.9369 -2.0486 TD (T)Tj 6.7246 0 0 5.9768 113.1023 286.6393 Tm (1)Tj 8.9663 0 0 8.9663 210.274 288.1133 Tm [(Regulation)-332.9(of)-336.7(cell)-333.4(cycle)-21348.7(1.97)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 292.0818 Tm (-)Tj /F1 1 Tf .725 0 TD (17)Tj 8.9663 0 0 8.9663 210.274 277.1716 Tm [(Cell)-335.7(division)-25927(2.60)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 281.1401 Tm (-)Tj /F1 1 Tf .725 0 TD (17)Tj 8.9663 0 0 8.9663 210.274 266.1732 Tm [(Cell)-335.7(cycle)-27033(3.02)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 270.1984 Tm (-)Tj /F1 1 Tf .725 0 TD (17)Tj 8.9663 0 0 8.9663 107.6031 252.2267 Tm (T)Tj 6.7246 0 0 5.9768 113.1023 250.7527 Tm (2)Tj 8.9663 0 0 8.9663 210.274 252.2267 Tm [(Transcription)-25763.7(7.07)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 256.2519 Tm (-)Tj /F1 1 Tf .725 0 TD (13)Tj 8.9663 0 0 8.9663 210.274 241.285 Tm [(Regulation)-332.9(of)-336.7(nucleobase,)-335.4(nucleoside,)-337(nucleotide,)-333.5(and)-336.1(nucleic)]TJ 1.998 -1.2203 TD [(acid)-335.7(metabolic)-334.6(process)]TJ 29.1676 1.2203 TD (2.36)Tj /F6 1 Tf 2.0802 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 245.2535 Tm (-)Tj /F1 1 Tf .725 0 TD (12)Tj 8.9663 0 0 8.9663 210.274 219.3448 Tm [(Nuclear)-336.2(transport)-24096.4(7.30)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 223.37 Tm (-)Tj /F1 1 Tf .725 0 TD (8)Tj 8.9663 0 0 8.9663 107.6031 205.3983 Tm (T)Tj 6.7246 0 0 5.9768 113.1023 203.9244 Tm (3)Tj 8.9663 0 0 8.9663 210.274 205.3983 Tm [(Positive)-332.8(regulation)-337.1(of)-330.4(gene-specic)-341.4(transcription)-11339(2.20)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 209.4236 Tm (-)Tj /F1 1 Tf .725 0 TD (5)Tj 8.9663 0 0 8.9663 210.274 194.4566 Tm [(Regulation)-332.9(of)-336.7(gene-specic)-335.1(transcription)-14570(7.75)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 198.4252 Tm (-)Tj /F1 1 Tf .725 0 TD (5)Tj 8.9663 0 0 8.9663 210.274 183.5149 Tm [(Positive)-332.8(regulation)-337.1(of)-330.4(transcription,)-340(dna-dependent)-10474.4(9.11)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 187.4834 Tm (-)Tj /F1 1 Tf .725 0 TD (5)Tj 8.9663 0 0 8.9663 107.6031 169.5684 Tm (T)Tj 6.7246 0 0 5.9768 113.1023 168.0377 Tm (4)Tj 8.9663 0 0 8.9663 210.274 169.5684 Tm [(Actin)-333.8(lament-based)-339.7(process)-19367.2(1.51)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 173.5369 Tm (-)Tj /F1 1 Tf .725 0 TD (9)Tj 8.9663 0 0 8.9663 210.274 158.57 Tm [(Endocytosis)-26272.7(4.42)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 162.5952 Tm (-)Tj /F1 1 Tf .725 0 TD (9)Tj 8.9663 0 0 8.9663 210.274 147.6283 Tm [(Actin)-333.8(cytoskeleton)-337.1(organization)-18181.8(9.32)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 151.5968 Tm (-)Tj /F1 1 Tf .725 0 TD (9)Tj 8.9663 0 0 8.9663 107.6031 133.6818 Tm (T)Tj 6.7246 0 0 5.9768 113.1023 132.2078 Tm (5)Tj 8.9663 0 0 8.9663 210.274 133.6818 Tm [(Protein)-330.7(folding)-25046(1.60)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 137.6504 Tm (-)Tj /F1 1 Tf .725 0 TD (3)Tj 8.9663 0 0 8.9663 210.274 122.7401 Tm [(Protein)-330.7(refolding)-24266(1.60)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 126.7086 Tm (-)Tj /F1 1 Tf .725 0 TD (3)Tj 8.9663 0 0 8.9663 210.274 111.7984 Tm [(Kinetochore)-338.3(assembly)-22147.4(4.25)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 115.7669 Tm (-)Tj /F1 1 Tf .725 0 TD (3)Tj 8.9663 0 0 8.9663 107.6031 97.7953 Tm (T)Tj 6.7246 0 0 5.9768 113.1023 96.3212 Tm (6)Tj 8.9663 0 0 8.9663 210.274 97.7953 Tm [(Positive)-332.8(regulation)-337.1(of)-330.4(glycolysis)-17975.4(2.54)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 101.8204 Tm (-)Tj /F1 1 Tf .725 0 TD (4)Tj 8.9663 0 0 8.9663 210.274 86.8535 Tm [(Regulation)-332.9(of)-336.7(glycolysis)-21200.1(2.54)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 90.822 Tm (-)Tj /F1 1 Tf .725 0 TD (4)Tj 8.9663 0 0 8.9663 210.274 75.9118 Tm [(Positive)-332.8(regulation)-337.1(of)-330.4(transcription)-16966.4(2.54)]TJ /F6 1 Tf 33.2459 0 TD ()Tj /F1 1 Tf .8852 0 TD (10)Tj /F6 1 Tf 6.7246 0 0 5.9768 526.3936 79.8803 Tm (-)Tj /F1 1 Tf .725 0 TD (4)Tj /F2 1 Tf 9.9626 0 0 9.9626 107.6031 737.4045 Tm [(SIMUL)-9.7(TANE)-9(OUS)-339(RECONST)-12.2(RUCTI)-10.1(ON)-333.3(OF)-340.6(MULTI)-9.5(PLE)-335.9(SIGNA)-9.9(LING)-10248(131)]TJ ET endstream endobj 36 0 obj <> endobj 37 0 obj <>/Font<>/ProcSet[/PDF/Text/ImageC]/ExtGState<>>> endobj 38 0 obj <>stream /GS1 gs BT /F1 1 Tf 9.9626 0 0 9.9626 84.0755 715.4644 Tm 0 0 0 rg 0 Tc 0 Tw [(We)-307.5(modied)-302.8(our)-305.9(approach)-309.3(to)-300.2(identify)-308.4(cell-surface)-315.2(receptors)-310.3(associated)-307.2(wi)-8.2(th)-300.2(phospho)-6.5(proteomic)-306(change)-9.9(s)]TJ -1.0015 -1.195 TD [(that)-380.2(occur)-379.2(in)-374.2(a)-372.4(model)-376.1(of)-373.4(gliob)-9.3(lastoma)-377.7(\(Fig)-7(.)-370.3(S7\).)-373.7(We)-381.4(use)-375.2(the)-371(art)-8.8(icial)-374.2(no)-7.2(de)-373.2(to)-374.2(represe)-10.2(nt)-374.2(external)-377.5(stim)-7.6(uli)]TJ 0 -1.2007 TD [(\(in)-7(cluding)-308.6(auto)-7.6(crine)-308(loops)-7.8(\))-304.3(that)-306.3(pote)-7.6(ntially)-308.4(act)-8.6(ivates)-310.8(multipl)-8.5(e)-304.2(recepto)-9.7(r)-304.3(molecu)-8.7(les,)-310(by)-303.1(connec)-9.9(ting)-310.2(this)-305.7(node)]TJ T* [(on)-7.2(ly)-277.4(to)-277.4(cel)-8.6(l)-276.7(surface)-289(recepto)-9.7(rs,)-278.2(of)-282.3(which)-285.4(331)-281.1(are)-281(present)-288(in)-277.4(our)-283.1(human)-282.3(intera)-10(ctome.)-287.2(After)-283.7(running)-283.2(the)-280(pri)-7(ze-)]TJ T* [(collec)-9.8(ting)-270.3(Steiner)-271.7(tree)-273.1(algori)-8.2(thm)-270.3(and)-265.8(removi)-8.9(ng)-269(the)-268.6(artic)-9.2(ial)-265.7(node,)-272.7(each)-270.2(subt)-7(ree)-269.6(will)-271.3(contain)-270.5(one)-271.5(recepto)-9.7(r)-264.5(a)0(s)]TJ T* [(the)-280(starting)-281.1(node.)-278.4(The)-277(rece)-10.4(ptors)-277.2(selected)-281.7(in)-277.4(the)-274.3(solu)-7(tion)-276(of)-276.6(PCSF)-278.6(represe)-10.2(nt)-271.7(thos)-7(e)-275.7(most)-278(closely)-277.4(connec)-9.9(ted)-274.3(to)]TJ T* [(the)-336.9(mea)-9.4(sured)-338.8(phospho)-6.5(proteomic)-340.1(data)-339.4(and)-339.8(are)-337.9(therefore)-339.6(likel)-8.2(y)-330.8(t)0(o)-334.3(b)0(e)-339.1(main)-335.5(cont)-7.6(ributors)-341.1(of)-333.6(the)-336.9(disease)-10.2(.)]TJ 1.0015 -1.2007 TD [(We)-387.1(applied)-384.3(this)-385.3(appro)-7.6(ach)-381.4(to)-379.9(p)-6.5(hosphotyr)-7.1(osine)-385.1(data)-385(for)-381.8(a)-383.8(model)-381.8(o)-6.5(f)-378.3(human)-384.7(GBM)-388.5(\(Huang)-387.8(et)-381.6(al.,)-382.4(2007\),)]TJ -1.0015 -1.2007 TD [(repr)-8.8(esenting)-420.4(phospho)-6.5(rylation)-416.5(differ)-9.4(ences)-414.4(betwee)-10.9(n)-410.5(cel)-8.6(ls)-409.5(expre)-9.4(ssing)-413(an)-413(oncoge)-8.2(nic)-416.6(mutation)-418(in)-414(the)-416.6(EGFR)]TJ 0 -1.195 TD [(prot)-7.8(ein)-331.2(and)-334.1(cells)-332.8(with)-336.9(an)-327.7(inac)-9.4(tive)-329(form)-334.9(of)-333.6(this)-334.1(recepto)-9.7(r)-327.1(tyrosi)-7.6(ne)-327.7(kina)-7.6(se.)-329.2(Th)-7(e)-326.9(resu)-8(lt)-331.4(is)-329.8(a)-332.6(set)-332.4(of)-327.9(11)-331.6(com)-7.6(pact)]TJ 0 -1.2007 TD [(tre)-8.8(es)-254.9(each)-258.8(root)-7.8(ed)-253.7(in)-260.4(one)-260.2(of)-253.9(the)-257.2(331)-258.4(pote)-7.6(ntial)-258.6(recepto)-9.7(rs.)-255.5(The)-260(select)-11(ed)-253.7(rece)-10.4(ptors)-260.1(in)-254.7(the)-257.2(order)-259.9(of)-259.6(their)-257.8(tree)-261.8(sizes)]TJ T* [(are)-389.1(EGFR)-10.7(,)-381.7(ERBB)-11.3(2,)-382.4(CD36,)-393.3(IGF1R,)-389.6(PTCH1,)-393.1(A2MR)-8(,)-381.7(SDC2,)-392.6(MET,)-391.2(ITGB3)-8.6(,)-381.7(NPR1,)-392.6(and)-385.3(EPHA)-9.9(2)-382(\(Fig)-7(.)-381.7(3\).)]TJ T* [(Al)-8.2(though)-263.4(the)-268.6(algorithm)-272.8(had)-265.8(no)-263.3(direct)-271.7(knowled)-8.1(ge)-265.1(that)-266.4(the)-262.9(data)-271.2(represente)-11.3(d)-262.5(the)-268.6(results)-267.4(of)-265.3(mutation)-270.1(in)-266.1(EGFR,)]TJ T* [(it)-354.2(sel)-8(ected)-353.4(thi)-7.8(s)-349.1(a)0(s)-357.3(the)-354(root)-354.9(of)-350.6(the)-359.7(largest)-359(tree.)-358.9(In)-350.6(fact,)-358.9(each)-355.5(of)-356.3(the)-354(four)-354.1(top)-357.9(receptors)-361.6(has)-352.4(a)-355.4(know)-7(n)-347.9(link)-355.7(to)]TJ T* [(cance)-11(r.)-304.7(EGFR)-312.3(and)-311.4(ERBB)-11.3(2)-302.4(are)-309.4(EGF-)-8(family)-313.3(recepto)-9.7(rs,)-306.7(and)-311.4(it)-308.6(is)-307.1(know)-7(n)-302.4(that)-312(EGFR)-312.3(is)-307.1(mutat)-9(ed)-304.9(in)-311.6(more)-311.9(than)]TJ T* [(50)-7.2(%)-464.4(GBM)-468.1(case)-9.6(s)-462.9(\(Cance)-10.9(r)-463.7(Geno)-8.8(me)-467.8(Atlas)-465.8(Re)-8(search)-468.3(Netw)-9.8(ork,)-465.6(2008\).)-472.8(IGF1R)-468.9(is)-466.4(overe)-9.4(xpressed)-469.3(in)-465.2(man)-7.6(y)]TJ T* [(tum)-8.6(ors)-324.1(and)-334.1(mediates)-334.7(prolifera)-10.5(tion)-327.2(and)-328.4(resist)-10.6(ance)-332.8(to)-328.7(apoptosis,)-335.6(and)-328.4(it)-325.7(is)-329.8(currently)-332.9(an)-327.7(anti-c)-10(ancer)-335.5(treatment)]TJ 0 -1.195 TD [(tar)-8.8(get)-268.6(\()-88.1(Macaulay,)-280.1(2004\).)-273.6(Becaus)-10.1(e)-270(IGF1R)-275.4(is)-272.9(also)-270.6(abnor)-7.6(mally)-276.4(active)-271.5(in)-271.7(GBM,)-275(its)-270.8(inhi)-8.6(bition)-274.6(is)-267.2(pres)-8(ented)-271.9(as)-272(a)]TJ 0 -1.2007 TD [(po)-7.2(tential)-338.6(therapy)-338(to)-334.3(arr)-8(est)-332.4(the)-336.9(tum)-8.6(or)-333.6(growth)-337.6(\(Kiaris)-340.4(et)-336.1(al.,)-336.9(2000\).)]TJ 1.0015 -1.2007 TD [(It)-245.3(has)-250(been)-251.3(previous)-8.1(ly)-249(shown)-253.6(that)-249.4(the)-245.8(EGF)-249.9(and)-248.8(IGF)-252.1(pathwa)-9.1(ys)-247.4(cross-talk)-256.4(\(Adams)-250.3(et)-250.8(al.,)-245.8(2004\),)-250.9(and)-248.8(IGF)-7.4(1R)]TJ -1.0015 -1.2007 TD [(med)-7.6(iates)-480.7(resist)-10.6(ance)-480.7(to)-482.3(anti-EGF)-12.6(R)-477.8(therapy)-486(in)-476.6(gliom)-7.2(a)-480.6(cells)-480.7(\(C)-8.2(hakravar)-9.7(ti)-479.4(et)-478.4(al.,)-479.1(2002)-8.7(\).)-475.4(Altho)-7.6(ugh)-480.3(CD36)]TJ T* [(funct)-10.3(ions)-337.1(in)-340(brain-s)-9.3(pecic)-342(angio)-8.4(genic)-340.2(regulat)-10.7(ion)-335.1(\(Kaur)-343.5(et)-341.8(al.,)-336.9(2009\),)-341.9(and)-339.8(the)-342.6(interact)-10.3(ions)-337.1(betwee)-10.9(n)-336.5(CD36-)]TJ T* [(Fy)-6.4(n-Yes)-263.1(lead)-265.5(to)-260.4(calci)-9(um)-261.1(and)-260.2(neuro)-7.6(transmitt)-9.3(er)-261.4(releas)-10.2(e)-258.6(\(Silverst)-9.9(ein)-262.9(and)-260.2(Febbra)-9.3(io,)-260.7(2009\),)-262.2(its)-265.1(relation)-264.6(to)-260.4(GBM)]TJ T* [(has)-278.4(not)-278.2(been)-279.8(studied)-281.3(in)-271.7(deta)-9.4(il.)-274.9(Further,)-280.9(the)-274.3(do)-7.2(wnstream)-284.8(interactions)-284.8(in)-277.4(Fyn)-274.7(points)-278.7(out)-278.2(the)-274.3(glutam)-9.7(ate-rela)-11.3(ted)]TJ T* [(prot)-7.8(eins)-247.8(GRIN2B)-251.5(and)-243.1(DLG3.)-250.1(In)-242.5(addi)-7.6(tion)-241.9(to)-243.3(thos)-7(e)-241.6(rece)-10.4(ptors)-243.1(pictur)-8.2(ed)-242.3(in)-243.3(Figur)-7.8(e)-241.6(3)0(,)-245.8(w)0(e)-246.3(identi)-8.9(ed)-242.3(PTCH1)-250.5(as)-243.5(an)]TJ 0 -1.195 TD [(im)-7.8(portant)-498.3(recepto)-9.7(r)-492.1(i)0(n)-493.7(glioblast)-9.5(oma,)-497.4(which)-496(is)-494.9(the)-496.2(root)-491.5(of)-498.6(a)-491.9(small)-499.5(subtree)-9.2(.)-489.8(PTCH1)-500.9(is)-494.9(a)-491.9(know)-7(n)-490.2(tumor)]TJ 0 -1.2007 TD [(suppr)-7(essor)-283.1(\(Agren)-281.7(et)-279.2(al.,)-280(2004\).)-285(These)-281.5(less-s)-9(tudied)-279.3(rece)-10.4(ptors,)-277.6(CD36)-284.8(and)-277.2(PTCH)-10.7(1,)-274.3(sugges)-8.7(t)-276.7(novel)-281.5(therape)-9.7(utic)]TJ T* [(tar)-8.8(gets)-333.1(for)-336.3(gliobl)-7.2(astoma)-340(treat)-9.2(ment.)]TJ 1.0015 -1.2007 TD [(Altho)-7.6(ugh)-383.6(the)-388.1(algo)-7.6(rithm)-384.7(is)-386.7(constra)-9.1(ined)-388.9(to)-385.6(identify)-388(inde)-7.6(penden)-8.1(t)-379.1(tre)-8.8(es,)-386.2(we)-382.8(can)-392.8(observe)-387.7(the)-388.1(pote)-7.6(ntial)-383.8(for)]TJ -1.0015 -1.2007 TD [(cros)-8(s-talk)-265.4(between)-267.8(different)-266.6(recepto)-9.7(rs)-260.8(by)-257.6(addin)-8.4(g)-256.8(back)-262.7(all)-260(the)-262.9(edges)-264.7(among)-265.2(the)-257.2(sel)-8(ected)-262.3(nodes)-262.9(\(Fig)-7(.)-256.5(S8\).)-259.9(We)]TJ T* [(no)-7.2(ticed)-428.3(two)-430.1(recepto)-9.7(rs)-425.8(sel)-8(ected)-433(by)-422.6(the)-433.6(algorithm,)-432.5(nam)-7.6(ely)-427.9(MET)-430.7(and)-430.9(ITGB3)-435.3(\(integrin-)]TJ /F8 1 Tf 35.6513 0 TD (b)Tj /F1 1 Tf .552 0 TD [(3\),)-430.7(are)-428.9(also)-429.9(very)]TJ -36.2033 -1.2007 TD [(im)-7.8(portant,)-316.6(despite)-317.2(the)-314.1(fact)-318.6(that)-317.7(their)-314.7(correspo)-9.1(nding)-313.9(subt)-7(rees)-317.1(each)-315.7(cont)-7.6(ain)-314.1(only)-313.1(two)-316.3(nodes.)-314.5(When)-320.4(all)-311.2(edges)]TJ T* [(are)-332.2(put)-323.7(back)-331(in)-323(the)-331.2(Steiner)-328.6(forest)-8.6(,)-324.7(w)0(e)-325.9(obser)-8.8(ve)-322(exte)-9.4(nsive)-328.2(links)-329.2(between)-330.4(thes)-8.8(e)-321.2(two)-327.7(rece)-10.4(ptors)-328.4(and)-322.7(the)-331.2(EGFR)]TJ 0 -1.195 TD [(subt)-7(ree.)-287.1(ME)-9(T)-285.1(has)-289.8(links)-289.4(to)-283.1(seven)-293.1(protei)-8.2(ns)-287.2(out)-283.9(of)-288(nine)-292.1(rst)-287(neig)-7.6(hbors)-285.8(of)-288(EGFR)-295.3(and)-288.6(to)-283.1(16)-286.1(prot)-7.8(eins)-287.6(in)-288.8(total)-287(of)]TJ ET q 430.485 0 0 180.283 74.154 107.773 cm /Im3 Do Q BT /F2 1 Tf 8.9663 0 0 8.9663 74.0976 91.8425 Tm [(FIG.)-296.8(3.)]TJ /F1 1 Tf 4.0783 0 TD [(Network)-296.8(representation)-293.2(of)-298.8(the)-289.5(PCSF)-295.7(for)-294.6(human)-294.4(glioblastoma)-298(dataset.)-294.2(Each)-293.5(tree)-300.4(is)-288.8(rooted)-297(from)-297.6(a)-292.8(cell-surface)]TJ -4.0783 -1.2203 TD [(receptor.)-243.1(The)-241(receptor)-240.2(molecules)-236.9(are)-239.9(represented)-242.3(by)-239.3(the)-238.9(arrowheads,)-236.3(transcription)-242.3(factors)-239.5(in)-237(triangles,)-240.5(and)-241.2(other)-234.2(proteins)]TJ 0 -1.2266 TD [(as)-337.7(circles.)-334.7(Terminal)-337.4(nodes)-336.3(are)-334.8(colored)-336.8(in)-331.8(cyan.)]TJ /F2 1 Tf 9.9626 0 0 9.9626 74.0976 737.4045 Tm [(13)-7.2(2)]TJ 34.5644 0 TD [(TUNCBA)-12.7(G)-334.4(E)0(T)-335.3(AL.)]TJ ET endstream endobj 39 0 obj <>stream Adobed       x  s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjzm!1AQa"q2#BRbr3$4CS%cs5DT &6E'dtU7()󄔤euFVfvGWgw8HXhx9IYiy*:JZjz ?N*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWbr_GڻՋ,+X~wcj%=x槚Z˞S[+߫ޘ㘤5)ad Ff4*??;[[A$"^ᛓRatb-,eCVɆ7[yr%>"Hث'Vum^ O USUثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWbV5 E£"f2~!2>,U޻ }%GȜøFY:wTwjh g+:06}“j6C˟ mi#o:xëi?2Og( Nc޿00xK^< m~?>Ꮞ{xn.|ߦa |s>K6>9 .e|,lಀ/~V$=-oa?f  _ضVٚ6Lj4&#ilO'x[SFX3oQ~jE[[vHLN'[TzdثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UĀ*v-[W rDuV~Mb\;cO(XƹL^P_Zۺ'h?Pe(UḢŪ߯*#)6Wh ~.#EBY*޷YOѶFeIԌ~S-~2F:V\aZnliZ7xiVsөDŽӫZ0<%Z1g1)oǀڟxDŽ[DŽ¼"cR?ڐ2RMl&Gt"n|Ȧ^'#a*~LȟNB@ QZY͟Cцb1\^Le}'U]BzJ~ںkWԆI*ˮXiuOUMV1z վ/C-̯D%ħSW.%x}[0.rW n_LUAT]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWbT 73X)12?\Z?jKwWչ J?]NcUE oט_GCɮE#@ sKe &y'YmlI(vvb~gh 4m{n\iP|?nT_ J e2d?Z3~$z-,^˴S«Z4O ӟi{#,2T<7H!?5VO(yOr?EZY*B_`܊x>RihHS NH9%\5'Z[?},1+X?8UifnQK%.um(z0Y|Uߖ_~b&+\5ѵ ]u DFFdo?5gY>h™Yǽ*-y.x_N@¢y, W+:2-~Iorr8W,HhVpHtE",e2|ZE- ޙUE&!Q]|*PO)LzC1I*,jј*s$lW\LC՞+ a*64Q^D}&|>@ͩXRӷF_ \1 E픜(()onr+cj 7fBۧW *]sm:ʜ91sKKYBޙtt=¾;7^Ej9Fza?n(n/} zjG-!<(,m{&> i0IB @Jgtͺ# 㱴DEnv*UثWb]v*Uثa56wffN] \Y$銱KuymG?@c`EWQ@*I;U'!bn $yzEQU^2! ]Wv* UiUTħo.u*\AO8 AToh{[?QK$0]tri"Q‚6g вǖS-Q±u/W2id:#l%Wd)<*>!D֚&+Zhz3ۭv >\c⩾a7 =QOZ}cK2<0N^&Q$t4baGv*UثWb]hUB]>aI!VR%wU` In.:{(b*/yu+r޴YDcG ƣliwi,t9 ǖA ._//'}Ƈ12H5>yBJjGTd:{1=BD2(u;75``?cBDa̤U'_63*UdL{>q~ʎh*jv*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثUKb0QڽX% 9\iMz9* ??#o0%@ϭNÌ@F2( &CY廂>(MncYq#}\8IQѩZY(ݓ E4ԮmNʞrɎ! !|P!^"$X@)JU_v*UثWb]v*UثWb]2-/M2ԍ@'9x/Zvĉ3 U<7|jZn4m{La j2ZR#S1TU։M>+"%ձerNAf.CAx'6uqg%̦i >͋ 銲UثT[{3%,Wg{hK;H#q[iWw5Kt調T~{v*UثWb]v*UثUfK>#I^XB05H.mVӮ/h_KMK%O2i&A?qsz3щ13$Ya#L㻆AR]!lG8:2"w$$C!"d6W ŐG-ܪ?zz͒SE*̨¯®]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWbrEv?@Nb<%ԫ0ތHs&eKm'S$msY, eDm $Ѧ`%wdZA(,2SH&icfzK>r 3*ByM.o.ɫ]b9 ~Rd&^g՘=S/Ow;fl4sd"ʴ zx "/;nI's12(BƁ@IW]v*UثWb]v*I|3=ƠM *g9c'׮4nM^Z).z]kXWb]v*skmsqȀB:(AVZiV|Bۖ4RjpO60b*"y٨73,U*OQ2xJHDH[XY=.nc?M2 ~Qˆn>-NK^C%~rӸy-ڏWҥ𞒏JEi(x Lp*?LeHfIB:\7)~AsJ UتW0y{Ch I+QF9<*i*<7ҭ n# u #hWcpMYw14(7VyZ\=6ݘQT v U J,WHU6<(~*{b]^:Q[bت`U"b"I?f8%y4ZOB:#նoɉ-}N&a_uO(!7 TaO (g#6#1j%i|d2w0KNQ8IA=әgEu Ī8Q>rJM]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثVg/Ũ=5Ʌ~,F∢h{[rOVIF!+vd旻I4\Jx튢d\h4EqzHE _Q¼ኽkpWu=ͽ|½=e`JT> jD ڮHw'N5K.il7z Ԓ!j:la3UbOV3'RHk~]_^ͭ\W>G_3YʹLR^;A0Wb]v*UثWb]v*Uk:ƱuwMէC umG:KRJ$Vi-!u_4Va7A.c8PTT0p\6-Zw.`*kWk5ҢnU#X2hӑo"qWb]v*Ӻ"v bh-mz ǧ%j?tD́#y?6װПڏxgy_{[lv0{Ke @wahc6pMpF] ^WzTY"XȜ>#| [u#EiRһleۘJ*t7m bmGp1HEXbA#yHv.?2xdo߿ގM_.:$ a~N8zڏ/\k t~Իmw\N&_22>ZY>W&s_B@t`YX::OKt?zx޼QZ=xTmrѼ9(L*>'E˭ plWLofi6'c4d01VD,2\Rƿ1MK[ Fџ[$ܿ쉣VM}W@_3Xk~_El뤟$5A3-Hz|`T{-{")m[K{]NKhQh^u 84뛋(.-dAWX˻}JdIin̠FvE'O3Yͬ+D J\V*UثWb]v*UثWb]v*U4@@e*F؄HX!'p?GEGF4F4x(`;[wt zmT| +/9B6(8@M6tO[󎕣^Kլ EN)9c~\+qSc%yc6V:e}9Mp H. Op<6Pwh9c`@^CEeN{O CkZy#Jvdg8}Grntga%(z`݀d6\|ƒƻe{| J?L@pUdQ'#$fNa)jW1ɴm+Zֱ2fm&YtᗅC-{Qo?ms''Q sk@-gk.e:%[?Vmi~V+ F~1>E5VN\@"*um.TV/fmcou*xbwC($*CiixÏq[Y^ڽ'RKG R0/O[*W~1T׷y6u\K=š6bj0S-zGֻ1אF{,ǂ1H L%a^V*ywmgi=Ԃ+khin)fcXtߚ0j躜p][$pF&14Â*}N$m*a˫ ZkaIo he65| c6E?ӡHV&Mс#WK6e=J&[l[V]NKp&x֕㊱#yVZzh1C;?ZLa}RTKfmPmauZTA~a@#|&ݨPo<674Iu5u7bW̔NO1Wb]v*U,?/ZGw] X&`<`X*jMve.d㷿gբ{4#)wBZ o&\j}1Kۦ"#f0 (xOm!C2,8ªGUSY=4SƲi9(4U-:Mݨ?n){+<~#2>e?Fw[?iXd?)?or,%+kE_|Gf;)ɖSFVb{>QPaImE6rV*tMX a68 va JzgHUG0ؗ?p'K.)a6|2^i9.}fnKNMӥiɐxJYZ4}II Cƈp*ܤ؛;@$&KWݏ˰6N9Xܠ"򤥺vdI2rwq9agRѸQo 4[KVY1~hry2(8=ˊL)vN]v*I8GIތY̏=4jĞʲv*Y/Q<%)lh4˨׈wLn]T&*VQGי$4kR} }OE#76ElUMei67q,@İh}C W~Oc(rpocVWS}mFi8/65<̥#uI!5=VoIz!aÖOčBGzI.x0k$s32%\ WJ@ٻjtc)~ZRGez6x=6=@kvTSIH)bX1҃ ;W -A$U"R9S2qHJ=4~O-Zبjq59pj44s*?<6mHkyV RPiiɰͤKF~/R;+GlqV' 6~NYH*d`(M:_ owpuhV2eVF(-T)n-q:NjmηVh%Jt=VUye+G򺙥#$x w[cOߚ|k]I}ϧsz l[$nkEp6ԝ銠 ZVimm=̶Otk'PX?TO,>q׵4yz7Q1} Ԅz- ܌LҜ&m7hg2?Ȝzej7xߩFaj Xtea#)ǐI ;>qci}J5+Bkg (_FZ-qC;_r6y<âvlu=Zj+ϧ֤b\Jȿ6|yM_ޞWySQQJrUUڦlUxTk=%v)VvU*%v$InN8 Wb]KM Ob)<`)ʛ#R򦭣Oc=݇'LPy11S&)eq?k9:2ZoP܏j O#J2 M~ʎ3cVf `pFd*UثWb]v*UثWb]v*UثWb]v*UثU9"9h;",[uq}K>j k:f>aɉ)Uf1Fb[m- ;MN8yf&>¶a=WЫ*.Քѷ6\R3bCoLռ-hzYp/9,Q<&݀~L~Y$[EV̗>e B6[H(~#^;^[m|\,iDO)xIe#`ҿ&bv*UثT-ESQcxЫ4ѯ0TkDA=Qme{rp2"*FZA~,8iHDC0ug j2r?5TUPxL " ʇP=ገ՗ 2 [>2-9Vb*IInjQ(嘱؂Pv-w?'o-ɔDpCS<{#LzQ'jT~?NWZtԷQ8paט#ثWb]K(-M//ӅiW4̍<&RcQvGmJG˹ʧ3)yW0#x(k*y{Ui C (E :p4˳Dh@SuwּOԵP,n/v ޢCuc&\@w}SG~xEMBMn9%Kǎ[p Gq7טV}7м˗z^&+UU*9Tjb *]SꖿZuhnfA/ * QJzeKWOztlʺӥլlQKs+icƓyr1?"2o+kp2j[iqin8B9\"<=gHWb'VGK{}q.-ӱsr. qXֲKB7>تhKi͌8cԭ["4hnăX@1k .QUQV]{sp$7 5%Cu mZec!M>ٍ_S=<}QiϗÁm-5{yFQ#(9,**Bi _)eez|i:lךeՍC4{j"nfGC_~*ʒb:o/G>WQyy@"ܭƋ!h^KR:b79u+7Dׯ,!(IFPבmS]#ziX\_iV`I%.i*ɱWb]v*UC Qɖ:a}Cu!$7hz-S?Xvm) EE:!>XƩN&V-,wԚrOL0 &pܡh|vͤ&$,6ZI]v*UثWb]v*UثWb]v*UثWb]V#A\0}#A((l]َwfcܱyrʀثWb]v*UتY,u&JC%O+&9lzUI]Z9H4 I;FD[33F9RXfzȳI<2|JRI]~jeċco)nu "q3SnVb?gyyvYP.KdI*fR?"biԴ`1:ίm;]huyQ*qb3A/pӤ0!i!CNO.a\1?P JW~+>~ \lDϙc5z4WF|-ӯ_N/AWa2ڹ &aySDliAim`+$o EȹY /,(XP^O4cRMv TY N54ʒ("@ pBY 'ت->E( فj}Zk%ثWb]C{lJHW^áAl2@N&'K<4g`/_NYI`8ķ_,jhbc:]cGQ$EGLKT, ;l=Jz R@`GCN0Ssa 4,TPWnJ@qc(GB^`K5CK?_ލ~["V#L1*\-»2FJ5 H޹iPp×*W1T:xP+s{v|F^ 8'mHWyFa n=~bᡬTZ!rUڃfWb]C_i@X=CHt[֯nz}1siؘunAFJvWi>U"}*56izS=ˬĩbg*S.H.H䆸t1)%~ʀUZ-|_6AMܼڀEn%تIgiȴ?H~mj&>h5%#?E1V_yW]c>gg)%}bK_WjP+qgH)6}~9=oFO\s2o"D`;|+ F]Aaj-,mHcTTPYH˼W5;Y0%IUթv2 1jP /B蓈I?3kb5#;B ާ}Fq,MJZξqO|h}w,+8n!aVEPrLUث*pKC[ {$G:=IQS(H=Bh3k7o"T?u1olǼHvoqcze:|>H)^dkI.4YZ6p+d(sH,;7>\6ZzQ[il[' CT W5̈́L$udPv-RO88gof[ J}<@ IXUv`s:bv*UتŽ=ĩ RK#E1BIhHo#+,CNAn(K:*C4l-35!kSŐ,&k?$u]si{żDfTtR7!IJQxWb֩ui, @9{ TX:bC#P ~$7(( G5d)wH݆j~NWԭ[I{$J@m9Wbw/WTc .@*B^:-*[7^Ge K4/;og@%ϨNsw~Ѐ2TQ%&"+!E2PU hNMOO'nVI{HIPA#+%h:no$7qՍi~ 4 (ӻayN4i[ydOoq޼QG|!,0ci͛ÏUtO+}(_@4r(YMjw q\$QfV^`nM @9reNz+bޭزm^ۈAm$;6ʤu8 ]?36U->F.;\Vnkz?+5gWӯ_y"עK~zp+ ˚|=|U`;(Y.uUBI$5Ⅎhw'[i0C{M.A3=A({Wb]v*UتQyrUd\u DEXPn}V&s[LcbC:J Q)C M*M %ӗ =Ol-Ͳ2M5Wb]v*UثWb]v*UثWbRF~ W=Na͉)E@8B3V,&w`(+- ayZ O(iO~au,^:][Ʊ3=7v*UثU5g{D*UI* *RN㓆ID4/,K/:})Yԫ7ø}C0gE FXZ~YWf-3PV ,?] |=(~x+'HPuy~[.K`}4TL'洫ū!hF~+̌+TN(k_Z}2\fZcnv*UثWb/<kr8KC /3|ܗv^s_̽g̗uַkIaf$hخZh<}8Ý%^Bl^y[t_"hia03 75P7PN]P dzo[ѭ\Zuf8EYmy]:e)z>*UثWbMZymۙFu9"$l>u S1%HI=C(y:`6YԨ0ލUثWbTn`EBF5czywkwk*MPG3>aeDN0SMVZ[Li@y$nnb̒wmÆ8QF]BjJoCrGy*i?$r)_+JYiwP:o̜$~ic%v-톮-=i5V{m-R%aG1Wv%;VOă2[C)siS^ʶYEldVxU*6Y$}B7<٭^͢eg'..[=K֬P>KqT}~U\G4m'"،eFs#PZ^,3L5#$Њ@铞[it#N{UgPʊX޴XsjZfY8WVߏ:xP)˴rqXܞZkMm˥V:YGNJ·-T&Or¿Ȧֽ׸1(`s7' wfYdiXպS,~!S+i7hH^j٦cdcOE|u]s]K%fXx-E,}KVTm9|sf1~Vkjγ\Nί$NmVEe\٥֎2U*(V5*b]v*UثWb]v*UثT&j Ryޡ_ynX-1Ϳ57P30WnCt3&)G8bv/=9jo.msv*UثWb]v*UثWb]5?`* 8vؒܯ)5Mie60P.;e!6V6p,0 DQ@Ldv*UثWb]C6dY|(!KM/$Ccd`,>fǐШ!F^X|ZT76cOGe4gßǿEW&3m?BP?Q:Pimqnp5gO'nz*UثWb]oo:J"`%a^EARWJLO{y=y!J0̤ˮؠƤ%1Iİr G>aWzf_rzY6z{$s%jK>%Rtd1똎v*UثPQ"дYSIU>*v#ɬa<@ Glv*UثUM1<8H;1RheK)gcj„H<{uS8cgǚ3V^Z] 9NY# ث ~廏/eB;#-涊Yh\#lq6B*G;#U0vc(mwI!H4)XGukv5xNXk^ 'ݖxpzeAhbzW>hw~Csm Z`4N'$BRJqV؀†ǔLM&c(CajiM}!tO(Y2cȫ(]v*UثWb]v*UثWbT/,ແC+εm˷FhMsVQJ_o:?PgyJ*):)WQ&؃S]/Qh],9w7ͦQ<"SdUثWb]v*UثWb]~v,T,mlR(dG!c0iVv U[yimh.HՏQHTZSnjrgrhׯ6_i2oVR@\|*E9IZ9sÅyWϚG|kq⹵R hlzpkdc*,H]h^n$mTCAYCmaaB35*UثWb]v*UثTH֡eE7"qo|'>|e &y=텥^B@ Pe>*u>,ǖP7} 머fj4C1zddlQ:k3Z)//&MK bȐUثWb]v*X'EU yV%r)@/|SNb\_by9]v*UثWbR6bK]ZTMy 14V(QH?F@dy !׬T2)vfE ⫿byjjg\{mʡ yS*Yneiqְ{OfY#gyN36x9UhqWڷ5khӃdYT7!Vݗ,̠Kq8qq}OcÓ0m1Җy㴚IJyq_UB?1g̝Ebm227#*bG]FU{VFPM(GcQRdTw߳M.ũ>[( e9oڎ**O/5-44 HTmk*(hf2XלyŨ^[;xag PFʈFb\_"LWT!{gIG~@a`<S]GLUثWb]v*UثWb]x|ia5鬴VJe7jiq"]O4A=$Orr\dC\GM+ JP8G+:yr}}|}En=FVge&'X{D==3UQiTMVQE ^Zmntek[;^+FmoM QƖ n.d%1q#I7RqWb]v*UثWb]v*UثWb5^ث}%n\ߗ㙐"kQ~!nَ vIPH +OeIދ""34^n6;ۉmZ rkn1T#g^_m-_KU@\ČjcffR '>KJմxghMo 4c'4<:28mdr,EfjKNFԹXGWv@@*nCbRngn?םXdKuL,{E6k 64{$iƭqQURX,\#O2 4浸ЭܳK(y1/KDIxU>]i6Z$fsāӵG'(9ҫ듄dߝRj:ݗOn g`%SGN~h&c{\B~Hة-ثWb]v*UثV;z/.KՈIFžKfWESeC_?i#vk"~0:  5åyȸo.Y?Ց̋>l^Q"u.Y\?{͊>V?0|׮᷶Fyq\UWb]v*UثWb]J|u$6IdX:I&f!rquNwso{m HDл38ZRnh}\ r ]ثT5ͼ\QJ2=B *li#O$c"xaA.Nj&Ӽ lڦG5I *<픥h/mL'ZrQ\Z@WCb]v*UثWb]v*UثU8* @Wb]֘Чg'/A*iMjp Ai:WKsw}"LqKND؜L)h|9qe>ʝVD'2O ;g`"W#*8.\ևaj֏. RH.%/$XRqo!!R\U$u/#0i֯=a# $q ލ]v"AP"b?HRK*#8Լ~u͋I>(/-۝Af@c'X 6&7$ 4O %ѱثWb]v*UتW^@g724q=P?44?[ޙw) 94wQ0^Gpr1!!hgkyy!i%+ $G@[v~;1z5Ltw[t d?>D~i*ʯ˸$A=Vcv*UثWb]v*UثU;{  3CA#pFi$(P으\B)ۑe2y)nv*Uث7wW#艤]( 7QOb$Kdm-gΟ^m ՚r[#+zf}E_Z핥ׂ׭qVV%W%5eNDHkGn"}:5<"і]{;{OV[ HdODq\WD[o =t˝NIX.5(Fp)"o%䤹8.h!4)`{ɧ֮'9v o#;SUNۍTu{2iac%R8ÇJOp˭Bӭg4wncH#y""VImFS}2 "}-SP]KPbwitXZ}&J8t|Mx~L~u~JO&`c?!G&6_\:ecbaѿQhjANVbP֝%LxI/H4% Q|Hz^z.(n|9bқSY<(8Z]y2<ٻv*UثWb]v*UثWb]H~sqF0K'b]v*UتVO)qf?,вUK5#WP|ir㕵hYds*BO5ɯEt9 '?_6ZL_Y"?8?-lO-n΢!m'UtIύ(iZW3UQǦ^=cFu d[c K 7(`<`3|JMz'SQ!-ΝH(5@ʩ͈M)#3oWixHz23׉%('H 4z*UثWb]v*UثWb]v*UثTY$ P Jp"bխ9+"(1$҇,:͜J1Wb]v*UثWb]v*UثWb]v*UتWs5zpYv3%HUTQ|Z1 }"ѶHLpʒiۊ3x~ nJ[V{/z#1t4]HlC2E,e 5'2{uD#կ.^]wi`rXR9A4@KޙR]t {xљdu ѳFd'*Hbo/?VhbfG/E8DXHjxT.gOm&*Mb&PIAۮNquZ HtHH#(@hYZW}F(vXiu~-D'y?K6Q;. TzU|$\e@pSIqqqHE(.tlOb2<8N!NĎQ,B&#ߑRfeiCAΜHk55xY)oXң\:} YG Gw) CZ޹4dږK^%dgj0|qɈW ~;M+GѵCpMwΖצ/*+,[AڙBWxb~?O5D@Mq0tp<>XF/5?$K3Ldf)^ 2!UثWb]v*UثWb]v*UثT&CWʩBaBދImwm^Ϥ@j+,i"[}eUyVITb@memuk {mB ES 7eEv{Y&4 nl)Ӯ*:Xio<0||2jE~ZعG&[ ߛ_,YNgv*UثWbKr#ZzP"e5rdmdl5,҃RҚ0ܮV+{BͷS6l|1!ت_I%@?ҭՋޟi U-O5;k[` '&@ߠlj;M_EdYv*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثTϞ_u-XẼ,2M 9qXG+I[;V xK6Hfyr^oku]^cė#Lj5#u˰L oJ^puGcgjB7l35 DRJY*UnXNTqƝxUտ掙+[/bO3zc'2Ng(ٔ(ZղxWz sGσ̚|0=ד;[D<i ?0H'w 2)ȓe/i]v*UثWb? y1-ɮ[M}U\|Jb"~w.IkLԵ1amt$bb+}U=+&O6\X[4.Eф1JЖBF&.##ݿ ="k+Ȗ{[1 /^h\:vf5uSv\D{v@{ecx{S.y[V֝s}ᵁؙ{8*<z1q%On\:<7ܝ.8Glӄ0|MraUj,7̲hgQP V%hϧQUӴ{a/$$nnc)͖1*(kWb]v*UثWb]v*UثWb]>aso%Hic> ̖YXEpTz۞aVZoٍ@Xto$ZźQNt=~(γB5%uI$5񸄉 SQM_jݠwW2 fQY%v*UثV= ^ w'0u(pK]19kc߫h/[ys'OLegJ8*ͻb#v*U%'Ut:;<_&Mdi/2 mmqͼsyE*CErĐydUثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWbPz?GͼI1+MR m"q0p5*QxB8WbX{rD420GWUɇ.fhgQُzSW yd˘Nr1ثWb]v*U^-,nb _XX.!}:=!/YY$~d~E֍}xscՕ}#څwjV^м|$fbL.F $D;KKHmcy!@;K! )Vw%6>j p̲AP[z-~IG.<:Px oV!QPxAVvYMe]v*UثWb]v*UتSOӮWxby#R5,B$`1WמO"kpkɬXyhu=5HdRЯ՝zcP$ U5^rY:d.n]}-xV̬ĞG-<ŭssA.6s|W&& q?ihWPsZ<b{xUmTYHj]*<à8)Z$Zsޙii|kmрA8?㊡ ɢ:ԣ:NrloLi8dBHlUv*UثWb]v*UثWb]v*UثWb]v*UثWb]v*Uث?4[.tMGR`$EqW~&CE?%dU\W֖q43$J#<+9Kn3d@ 9 (H2 k-4Ʃsp 4^4-nmTxYTcRU2*0QϘY='X#1z1-U_XyXKs65&'|0&sA;ZEkznY`!Za iMB jp뛰)v*ԧ :xE U$b7R=MKJY&6fIijӔ qF*k̯2^YΥi{n-a9M9ifDWepE +_ͯ8]%Ek{ayym rbX"KoIXy]ISVEJ}獼:4i%@V4DEs"8^y Bvh_>dԴ_)\sƱ$eF0^ @a^$Pbk/?Ӯ "~aF|U_VKY\KKɍYؙHIޮYF7V蟖ZZEymCI6p nֶnի~O/8q D$hiMZ+)WK.`Rzytr--G4UY`X-%))'f~,USy^4U]GN5{{B%h@1TEW-_jMϘcm=܉!^M7S5$|@2 ^eԴ]7AQkە%h3a"~g##gdUثWb]v*UثWb]v*UثWb]v*UثUAKxB8;ד.jG*(b8hc*BjUh61V5]DkeV+pbE)! | EWJ䊰P%edٸSB+ify f8%0@<ґ^,N?7|:!UXHUTlhy{]%$<|«8S'wY[h }ZZC;TI)jPp14y*jk1{(Hw/ȴj$h;k\%=a_Lu2~9"?+MIBzQ;wr /:d@2$]%( B1 A@ԦiPshZ4ǓB7޴9tu9p/1'wuofu~hD?U/ նmn.D2,>ew^%M#֊g˦UJ~d({cɑB]bzuXDf[;w5ȡ$E:=I*G68s,n]iYJ (w@A[i۪,K F#C)TlU H)&"j(Z@bH-2kL9ޠ<~ RfLU)9n<40Pc i,3ucS\=̶P:gzv*UثWb]v*UثWb]v*UثWb]v*UثWb]u/lLQ%VY#(kCFTm>.8:%14!JV(=|rPum1)r 1ñWb]v*UثWb]v*UثWb]v*UثWb]I.\A7d ʅy)=9 քCC!LlCNǫ1NBF͹GrWUتW5Ž婳p^"Yy)UFb@-:  =.DwsVc:%Sv*UثWbR'g:@t8$?J:b]v*UeY@Wٚl9j+ iS-WANfRq,6l݊E'`+{6g3۹vٚ$KQjN3{dB?u|w)OkOm .KWb]v*JWVQ::#8% Ѻm\#Zخt!ղ&ROIocoerGt#1Y;v*UثUFFѸ R_rSԼ˽o,[k:^B̗kP#\CxɟZhխF_KᵖYAO5k>%jCW*Jio(Ƴ%H.!Ai/-:x~Y徉ikyMulchг+HQ ULU]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثTΥ?QnUߌlp?B41UثWb]K5I7p13p?NQE?1~t697TU,"yWcռXS-|񢥓A+ YJ9@tV[VW򆉪k{/,Jv8ޙ4s+h[toMs&3?hw k̲k_ҵvlo-`+o5Ǩ&痤! O"mߛo."HmocA"_Rnή6iW)JwaRȗpj0+q so,!T4ȾkbQ]v*U ug"Kt!a6Vkl嘌Ty_M 7כMȳdUثWb]cZ݆>n<\nyVF%$;0X9hHSxF0M*9 wcٷ'>?cWb~o,# /) FDDEj%Uh<_yg%(s_s sMWb]v*UثWbV1˅G.5iᆖ`Wb]v*UثWb]v*UتYiS_Lvdy Uw$U _̿#DV4iGIQ!+ 6 Aت?~M=M 3&$+U#1 ~qTJtZ+:u%Zԕe R*UHσ0TJ@G,S R}NaHnjҢ Bɮqwv*%1Te_4_,U 'wOa*1Un֚O1U&fяImXp^,@|m_6i$6U͚oΟ''WZqur6V.*_FηuUVDJã84PGu2z=YGU.(OX_\UXkIw:PKv/%˓ɞY>Nw)+/C}Ym[]"5=:Ga98FfYWL+ F UWb]v*UثWb]iUK1 *vI:T eh݅N?4=˧S5GxtNb]a۵֡ت6=fŘ$m=`S'?AQ*7]v*UثWb]^ԵI]tK{أ.фHRۛm^˸csڸr^]r?H\j1Eı5F>5} wl( ثWb] VduV;xToL PW(cBF(.]v*UثWb7s"rxR h?@d?KP9#rv*UثWbcJUtK?cꇠ$}v)iپ}OK2tGsn/5}e\ԥ;g(ӯ龀92̽.]v*ÿ5fռ!xnbQ䎼VWe^UGLU{xkksX_#2ոa UN&~ij:|v3Ykuvc1ԑPAеM*Wrkz5ݔney+v`V3W?z|vF*~RyZ״F=fuHĊ!kxNOnL ՐY*UثWb]*b:wVg^}Vk)ց e(?P6 K~z^Z$\1W# r4|ZHsܚ[\[qo"4r) R` UثWb]v*UتT2I1oRvT$vi),B8ѵ}C.i$v}I&Kq/a?[L~eoݿX_:/k[F/ec Bg4[oSKV5q#ypGX*9uKk M Uus U1r}yw*VfQ~Qg?378*?ʯ./XT׊J?t_銯q]*ˇп+1U9?,_銡}~@ՊӿR]8=ntolX{Yi_@⬣-W΢K~UyX[D[#>-b,Qd8DgdK"!BEH&*mYP }LU17zb\HG⩕XnqTv6{7?W6ث Q?ߐ?qTPД3~jhF*]v*UثFs`.tˆ> HKSش ^BU!ӛ!ȋ,qPF"ײd(" v*UثWb]v*UثWbT5K NY=SID_QG$^Tb]v*Uy8|'ÌSKRdf]{k'eo&<ލxܽeFi?Yk5)9x]){7jsshrv*UثWbII{e0a]ivڌij8GiAD#Pl 'QWb]v*4A{(.ݹ۴$6B?,UMXyzäZ[[?; `3 ֿٙ@q{N +U%6i뵹.R4c-A~.=]F~n-- ' Db]v*UثWbX2XkזCz |Ґg`W˭s;2q8d$a 8U TQ@0\Wb]v*Uت Ws4z(fq$} '?iۯ1bA> )_*MpyJU[WFzuIbV^H P1V3i"5y#u?L<1cE !|HڜUyCCPۭA@*Eeiq*U]v*UثWb]c~}m"R.Ku(y"VtAݚIbO41e4]DAg{1K=OJ=M~*:ZO7[WV>rdW ũ b8"u 7JUVm}Khuֶixnfkb?8 CLU4Fx< #XEXLn*|JA 7޵*>sjo`:_5T\7J2 !r>GMmEEr+eRUqM?̗ 8,vWi:>uq0S*]v*qagq=Z1{iT2%~jrBDTrE.]v*UثWb]v*UثWbYʸ{ɤt:K/5$z.Q =zևIuCes[I7mROH7+Ww ӮOz /GU:|rqX $k~BSmnDeN:D³[YʙTL| PIJLSUثWb];}&2GPy%)G4Iv_iu7}2?Gr.kQSsO\Os/A}NK?CF7S 3!.]v*UتN&@ E{K5$7,AbXMNܩ*$u6@M3.]v*UثTVђ'q*G%*w£N1qhZHiC,9RZ~34hs)Av*UثWb]v*UثWb]v*UF-Ă4 '>ceu5cgm]ǹbzL6!۩>'Tk iJ5~lqpzCM6_Lt%X`ݗ㒞~WdOd4vގ][: dۏnT*Q~[=zfL.WPdOUx$r*m|g7+k+Y6b7WEr+/&#ԭ*|aS^ԭX VnAx--ӷN%` zvY*UثWb]v*UثWbZE;*+@MO銶Q@6tv*UW@m4*IMV!VJZ[6ꇍ~cF*5/HcEG}XdbȿiaS*ApybVO^"w:&⬫MK>|J?~UE,SFHU]MAbWb]v*UثWb]v*UثWb]-[h%զV ^x3G}+Uh6:eơ ۋhZrf[xt:2Q4A*G'ZVKx=2ۅ xS]DlYay`X2`T~*UثWbX{C5>rJGAvQ5ԴkaJ̍7G3pn1i"?k3SsTos[f.R3k>ȳ dUثWb]K>bqo-d}X/LWb]v*UثWb]v*UثWb]v*UثWbR[]ZEPjFUj:I$@e@{"qTIX3犤i Zk99AqTED;S*O~*} Z& (#S|qTUTQ@b]v*UثWb]v*UثWb]v*UثWbVI RY0=AXνjYc7V]>n1WVZwBjPve;|;U3 mO4n{g, joGqVmkE%eMt>Tv*UثWb]v*UثWbX杷|&$ZŴ]D Wy_(P^_+~u]W+^{0P° qEGA^^8RGK"ӯo.f6Z[h\@}b2+uVi]TUӬӵ|g&..%1EpSiTPR/5]>̅VCb-Xn< P5[HzOvx5o?T?ދ*-2\hhUT;3O${̞T1ƕX6ރ(J'v*UثWbXלcGӖb%kK&_W̚$CZ4gQ60}m}/5<1ҵS3[XI~`kʬ"UgoZ/?aYgv*UثWb]M{XQ0_=L) xdU3:ȟeA;fFDhAri T]ffHTrL`::S/A ׋wmT2P28VZ\U3]v*UثWb]v*UثWb]v*UتWouE֖?x:zDp_e_aiẇ a+]f1XQ՘qT= OjIkڜ_(㶵ݺ( $i35jLU,sUQE[]v*UثWb]v*UثWb]v*UثWb]v*UتaT)"SU*l~^?jZEu8TIm4lU hqTfugvMgQԭ ޜP]%IC\UxZ_0RB!z\R8X\l'%qii/SKKO%Җ h:APdVNV[-j}g@aK{Sͼ ߏ*b]v*UثWb]Rehg st-āۍzJ̿ 4ߞwdV:Rz***A}?xȌЏ*zm?V#'8ccY3NQҖ\kְKHr̘zq_uL.]v*UثV+E8v!F`055 wӔti?yY蹲füi4Eo}~Z )P3XևyLe2[JdIYmv*UثT&.y$qj2C"-}4f b"O2ysM[ Zi Xm]s1$G*ƕ.0 ָvtųI⨯͘w>Y]ofb?V# Xne <?_`*yWZ2_H؂&èi柿z原keUbUثWb]v*UثWb]v*UثWb]v*UثWb]v*UتYh~lƭRWy>KSknZ1⿫_61A cy8/Wך2/J5nQ~bWU4KZ]F3?QNQb}t vc|UثWb]v*UثWbR?Cc쵧%j?-9bR__cp~}NatYMrScE'0ء^pwGwfvfEl>Lgϐё]#8[u*~Vh$ ^Rz bymb2ALt6OuC:$4.,w4eTm7s%ŭ 2UYH؂2b]v*U )'X-c=s+>D3I\S%~0ʂr=n+tss@6Ǔ1ҁ,snݑ:`"+ ѧ2F[Ň.eHT2GC!}\y~9G9.(.]v*UثPQHADPUثWb]v*UثWb]v*UثWb]v*?1GSE,-ͶTu&Y&!U"VYU,u["|hqV!uiwo-OMmfꭦs~(^])*|ϧ[yϺ."m8%nViA#aYQhEUثWb]v*UثWb]|}/PмgZʾa!aƕq%Nd[cqbkZΟ#[ ][j,g!Op1$@g1VsyCzkkKM WZ+YjD^G suVNJH$wXk%(Q6֬}[tYNj*)eتse1u9yW֐Yjz^ҥ u⯥A:Wb]v*UثWb]v*UV17M*sZ?{hdU U.?(! "`AXW Po%~CL<}Yy^[d llOj?pØX|S]䒺go6ni"~cv*UثWb]v*UثWb+;CYiЫ=d_Rը6&BS㊥-?qu{>8BkKȋO1Ҏ&A~WyM$-wJ 7rV~nlj&]ܾ,85{_Q<47ikVd2ђ_QCj@L#.{y;F/K:+ieqBc^?: Tv*UثWbwnGu4ӏgGd IAc1"8DP3DԗylT$MJC1?6VNob(SjoZ` zUi﬎zd%\SkaQQ ' u(|͞vleثWb]v*UثWb]v*UثWb]v*UثWb]v*05.PH~;L(JrbBqKľ%,1Wц@㊎B~\SoKmOx= ǣ^<^,iZc7I$JʡqPA;ov*UثWb]v*UثWbR3>YM .{0FkϾ*Ȱybo+EZ6±3 ʇ~UQCZUo-|ۋkDH !%N*aUspkeAxф^NMHQQ_*= @]ҽ݃ hB HCW튨yS>R{<[i]'q"gx^^1TeIidxY=İ8~U*?..$ߨ&7*Ғ2WqOV,]v*UثWb]v*UثT\GoD!KI$2 y,L!'*C˭2X4lʡ)%XT*ΑQG@B9EO*L'gK0q$(Q1 xbA[eP@^4NثӼC4[I2G?SUثWb]v*UثWb]uUە1 hN͌5ͅ1G Ev2E<s[=8C40ޙv*UثWb]4MYq(_?ZkZƬsX֑jqCYt*ί(}ZX\D=AͳcxV/MT9p9N{3umA0)><%J+_TRF18ї8J 6 ݊v*UثWb]v*UثWb]v*UثWb]v*UثWb_rmֲ TWj8Y'<\U2n^_jZ";En›R~qVyv*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]97y> endobj 41 0 obj <>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 42 0 obj <>stream /GS1 gs BT /F1 1 Tf 9.9626 0 0 9.9626 107.6031 715.4644 Tm 0 0 0 rg 0 Tc 0 Tw [(the)-325.5(EGFR-r)-10.5(ooted)-327(subtree)-9.1(,)-319.1(and)-328.4(ITGB3)-327.2(has)-329.6(links)-323.5(to)-328.7(17)-320.2(membe)-8.7(rs)-323.4(o)-6.5(f)-321.4(the)-325.5(EGFR)-329.4(subtree)-9.2(.)-319.1(B)0(y)-330.6(contrast,)-331.7(IGF1R)]TJ 0 -1.195 TD [(has)-295.5(links)-295.1(only)-290.3(to)-294.5(three)-296.6(proteins,)-295.8(and)-294.3(ERBB)-11.3(2)-291(has)-289.8(links)-295.1(only)-296(to)-288.8(tw)-8.2(o)-291(proteins)-295.4(in)-294.5(the)-291.4(rst)-292.7(neig)-7.6(hbors)-291.5(of)-293.7(EGFR.)]TJ 0 -1.2007 TD [(Altho)-7.6(ugh)-486(this)-482.1(inf)-7(ormation)-491.2(was)-487.2(not)-488.7(applied)-486.8(to)-488(the)-484.8(algo)-7.6(rithm,)-487.5(MET)-487.6(is)-483.5(dete)-9.4(cted)-487.4(as)-482.5(dif)-7(ferentiall)-10.9(y)-484.5(phos-)]TJ T* [(phorylat)-9.7(ed)-401.7(in)-396.9(the)-405.2(original)-405.1(data,)-402.4(and)-402.4(a)-400.9(MET)-407.9(inhibitor)-406.8(synergizes)-407.1(with)-405.2(an)-401.7(EGFR)-403.4(inhibi)-7.2(tor)-399.7(\(Hu)-8.2(ang)-396.7(et)-404.4(al.,)]TJ T* (2007\).)Tj 1.0015 -1.2007 TD [(Mammalian)-282.8(sign)-7(aling)-278.6(systems)-278.7(fre)-8(quently)-280.1(demonst)-8.9(rate)-278.8(a)-270(high)-279(degre)-9.4(e)-270(o)0(f)-276.6(cros)-8(s-talk.)-277.2(If)-278.6(two)-276.4(recepto)-9.7(rs)-272.1(shar)-8(e)]TJ -1.0015 -1.2007 TD [(many)-366.9(com)-7.6(mon)-370(downstream)-377.4(component)-11(s,)-366.5(the)-365.3(algo)-7.6(rithm)-367.7(need)-370.8(only)-370(choose)-367.8(o)-6.5(n)0(e)-367.5(o)0(f)-362(thes)-8.8(e)-366.8(a)0(s)-363(a)-366.7(root)-372(node)-369(to)]TJ T* [(explain)-446.9(all)-436.4(the)-439.3(termi)-10.9(nal)-439.3(nodes.)-439.7(We,)-444.4(theref)-9.2(ore,)-438.9(introdu)-7.2(ce)-437.6(a)-440.7(perturb)-8.1(ation-b)-8.9(ased)-440.3(appro)-7.6(ach)-438.3(to)-436.8(im)-7.8(prove)-440.1(the)]TJ T* [(sensit)-8.6(ivity)-427.5(of)-430.3(the)-433.6(algori)-8.2(thm)-429.7(in)-431.1(identifyin)-11.1(g)-427.6(recepto)-9.7(rs)-425.8(that)-437.2(share)-431.7(man)-7.6(y)-427.6(downstr)-9.5(eam)-430.5(com)-7.6(ponents)-432.2(with)-433.6(the)]TJ 0 -1.195 TD [(selected)-338.6(root)-332.1(n)-6.5(odes.)-330.8(In)-333.6(this)-334.1(analysi)-9.9(s,)-326.7(sel)-8(ected)-336.3(recepto)-9.7(r)-327.1(molecu)-8.7(les)-332.4(\(th)-7(e)-326.9(root)-337.8(of)-327.9(the)-336.9(largest)-336.3(tree)-335.7(in)-328.7(the)-336.9(forest)]TJ 0 -1.2007 TD [(and)-402.4(other)-403(rece)-10.4(ptors)-402.4(in)-402.6(its)-401.7(correspo)-9.1(nding)-404.9(subfamil)-8.7(y)-399.1(availa)-9.8(ble)-399.5(in)-402.6(the)-405.2(forest\))-404(and)-408.1(all)-402.2(their)-400.1(int)-7.8(eractions)-407.9(are)]TJ T* [(removed)-333.1(from)-323.5(the)-331.2(interact)-10.3(ome,)-326.7(and)-322.8(PCSF)-329.8(algo)-7.6(rithm)-327.8(is)-324.2(applied)-333.1(to)-323(the)-325.5(remai)-10(ning)-324.5(networ)-9.3(k.)-319.8(Th)-7(rough)-324.5(this)]TJ /F5 1 Tf 42.4174 0 TD (in)Tj -42.4174 -1.2007 TD (silico)Tj /F1 1 Tf 2.5209 0 TD [(kno)-8(ck-out)-346.8(experiment)-12.6(,)-341.8(w)0(e)-348.7(can)-347.3(nd)-342.9(the)-348.3(other)-346.1(recepto)-9.7(r)-344.2(molecu)-8.7(les)-343.8(whos)-8.2(e)-344(role)-345.3(may)-349(be)-344.7(masked)-348.6(in)-345.7(the)]TJ -2.5209 -1.2007 TD [(presence)-340.8(o)-6.5(f)-332.8(the)-336.9(recepto)-9.7(rs)-334.7(in)-334.3(the)-336.9(initial)-339.6(forest.)]TJ 1.0015 -1.2007 TD [(We)-358.7(rst)-366.7(knocked)-361.7(out)-363.6(two)-361.8(EGF/E)-9.3(RBB)-363.6(subfamil)-8.7(y)-359.3(recepto)-9.7(rs,)-357.9(EGFR)-363.5(and)-362.6(ERBB)-11.3(2,)-359.7(from)-357.7(the)-365.3(networ)-9.3(k)-353.6(and)]TJ -1.0015 -1.2007 TD [(regenera)-11.5(ted)-376.7(the)-382.4(PCSF.)-381.4(In)-379.1(the)-382.4(result)-9.4(ing)-374.9(networ)-9.3(k,)-376.7(37)-382.8(out)-374.9(o)-6.5(f)-372.6(42)-382.8(nodes)-382.4(in)-379.9(the)-376.7(down)-7(stream)-387.5(of)-379.1(EGFR)-380.6(in)-379.9(the)]TJ T* [(origina)-8.9(l)-299.4(tree)-301.6(are)-309.4(connecte)-10.3(d)-296.7(t)0(o)-305.9(other)-300.6(rece)-10.4(ptors.)-306(Platelet-der)-13.4(ived)-303.5(growth)-303.5(factor)-310.8(recepto)-9.7(r)-298.6(\(PDGFR)-11.9(\))-298.7(i)0(s)-301.4(the)-302.8(root)]TJ 0 -1.195 TD [(of)-356.3(the)-354(largest)-364.7(tree,)-358.9(covering)-361.5(23)-354.3(nodes)-359.6(linked)-359(to)-357.1(EGFR)-357.8(in)-357.1(the)-354(origina)-8.9(l)-350.7(networ)-9.3(k)-353.6(\(shown)-358.8(in)-357.1(Fig.)-357.5(S9a\).)-359.2(This)]TJ 0 -1.2007 TD [(observat)-9.9(ion)-460.3(sugges)-8.7(ts)-455(that)-465.6(PDGFR)-464.4(may)-462.8(have)-461.9(man)-7.6(y)-456(overlapp)-8.7(ing)-460.3(functi)-8.2(ons)-458.7(with)-462.1(EGFR)-10.7(.)-455.6(I)0(n)-458.8(fact,)-467(several)]TJ T* [(studies)-305.2(have)-302.5(shown)-299.2(that)-300.6(PDG)-9.4(FR)-295.7(is)-301.4(critica)-9.6(l)-293.7(i)0(n)-300.2(brain)-300.6(tumoro)-7.2(genes)-8.6(is)-295.7(\(D)-7.4(ai)-296.3(et)-302(al.,)-297.1(2001;)-302.5(Uhrbom)-304.2(et)-302(al.,)-297.1(1998\);)]TJ T* [(mutation)-378.2(of)-367.7(PDG)-9.4(FR)-369.7(cause)-10.4(s)-371.8(alteration)-378.8(in)-368.5(the)-376.7(intracel)-10.3(lular)-371.6(sign)-7(aling)-369.6(\(Cla)-8.6(rke)-370.2(and)-374(Dirks)-8(,)-370.3(2003\),)-370.4(and)-374(it)-371.3(is)-375.4(a)]TJ T* [(therape)-9.7(utic)-363.2(target)-368.5(in)-368.5(GBM)-365.7(\(Ziegle)-10.5(r)-361.2(e)0(t)-364.6(al.,)-365.3(2008\).)-370.4(Another)-368.6(14)-365.7(nodes)-365.3(down)-7(stream)-370.4(of)-362(EGFR)-369.2(are)-366.3(shar)-8(ed)-361.8(by)]TJ T* [(MET)-288.4(\(seven)-290.2(nodes\),)-288.7(IGF1R)-286.8(\(ve)-284.9(n)-6.5(odes\),)-288(and)-282.9(ITGB3)-287.4(\(two)-290.6(nodes\).)-288.7(Altho)-7.6(ugh)-281.1(these)-290.2(four)-285.8(recepto)-9.7(rs)-283.5(\(PDGFR,)]TJ T* [(MET,)-311.5(IGF)-7.4(1R,)-308.2(and)-311.4(ITGB3\))-312.9(capture)-317(many)-310(of)-310.8(the)-308.4(nodes)-314.1(that)-306.3(wer)-10(e)-304.2(down)-7(stream)-313.5(of)-310.8(EGFR,)-312.7(ve)-310.6(nodes)-314.1(are)-309.4(not)]TJ T* [(capture)-9.7(d)-330.8(b)0(y)-337.3(any)-334.1(othe)-7.6(r)-332.8(recepto)-9.7(rs.)-335.1(These)-338.4(may)-337.7(repr)-8.8(esent)-335.7(sign)-7(aling)-335.5(that)-340.4(is)-335.5(uniquely)-337.8(down)-7(stream)-342(of)-333.6(EGFR.)]TJ 1.0015 -1.195 TD [(To)-416.7(further)-425.5(expl)-7.6(ore)-421.5(the)-416.6(networ)-9.3(k,)-422.2(we)-417(rem)-9.6(oved)-420.2(PDGFR)-424.5(in)-419.7(addi)-7.6(tion)-418.3(to)-419.7(EGFR)-426.1(and)-419.5(ERBB2)-12.1(.)-415.8(I)0(n)-418.9(the)-422.3(new)]TJ -1.0015 -1.2007 TD [(networ)-9.3(k,)-245.8(the)-251.5(MET)-254.2(recepto)-9.7(r)-247.4(partially)-256.8(replace)-11.5(s)-246.6(PDGFR)-9.1(.)-245.1(I)0(t)-251(has)-250(been)-251.3(show)-8.2(n)-245.5(that)-255.1(the)-251.5(MET)-248.6(rece)-10.4(ptor)-246.8(is)-250.2(act)-8.6(ivated)]TJ T* [(in)-266.1(GBM,)-269.3(and)-265.8(it)-268.8(might)-268.9(be)-265.1(a)-270(therape)-9.7(utic)-266.4(target)-271.7(\(Li)-268.6(et)-262.2(al.,)-268.6(2011\).)-273.6(Similar)-270.5(to)-266.1(the)-268.6(MET)-265.6(rece)-10.4(ptor)-263.9(tree,)-273.5(the)-268.6(subtree)]TJ T* [(contain)-8.7(ing)-460.3(ITGB3)-463.8(rece)-10.4(ptor)-463(also)-458.3(collec)-9.8(ts)-460.7(several)-466.2(of)-464.4(the)-462.1(nodes)-462(previous)-8.1(ly)-459.5(assoc)-9.8(iated)-462.5(with)-462.1(EGFR)-466(in)-459.5(it)-7.1(s)]TJ T* [(correspo)-9.1(nding)-279.7(subtree)-282.3(\(shown)-279.1(in)-271.7(Fig.)-277.8(S9)-6.4(b\).)-271.3(It)-279.4(is)-272.9(intere)-10(sting)-278(to)-271.7(note)-280.8(that)-277.8(integrins)-281.9(functio)-8.9(n)-273.9(a)0(s)-272(both)-279(upst)-7(ream)]TJ T* [(and)-317.1(d)-6.5(ownstream)-325.4(effect)-11(ors)-318.4(of)-316.5(grow)-9(th)-317.3(factor)-322.2(recepto)-9.7(rs,)-318.1(such)-324.7(as)-317.5(EGFR,)-324.1(IGF1)-8.2(R,)-318.8(PDGFR,)-322.5(MET)-322.5(\(Alam)-325.1(et)-319.1(al.,)]TJ T* [(2007\).)-461.4(Integrins)-463.2(and)-459.3(their)-462.7(relation)-463.8(to)-453.8(GBM)-462.4(have)-461.9(not)-460.3(been)-456.2(stud)-7(ied)-456.4(in)-459.5(detail,)-460.7(which)-461.8(may)-462.8(have)-461.9(clinical)]TJ T* [(importanc)-10.1(e)-332.6(i)0(n)-334.3(GBM.)]TJ 1.0015 -1.195 TD [(During)-331.9(all)-334(these)-330(lea)-8.6(ve-one-r)-9.9(eceptor-out)-336.2(tes)-8(ts,)-330.2(IGF1R)-332.3(is)-329.8(pres)-8(ent)-331.2(in)-328.7(the)-331.2(resulting)-338.8(PCSF,)-330.2(and)-334.1(it)-331.4(retains)-336.3(all)]TJ -1.0015 -1.2007 TD [(protei)-8.2(ns)-440.9(in)-442.5(the)-445(ori)-7(ginal)-443.6(networ)-9.3(k.)-439.3(Th)-7(e)-440.7(down)-7(stream)-450.1(networ)-9.3(k)-438.9(o)0(f)-447.4(IGF1R)-446.1(starts)-448.7(with)-445(the)-445(estroge)-9.2(n-recept)-12.5(or)]TJ T* [(\(ESR1\))-365.1(intera)-10(ction,)-364.3(and)-362.6(it)-359.9(contain)-8.7(s)-360.5(several)-363.7(MA)-7.4(PKs.)-365.5(It)-359.1(has)-363.8(been)-359.4(show)-8.2(n)-359.3(that)-363.2(ESR1)-365.3(and)-362.6(IGF1R)-366.5(are)-360.7(cros)-8(s-)]TJ T* [(regulated)-349.8(in)-340(the)-348.3(brain)-346.1(and)-339.8(act)-8.6(ivate)-343(the)-348.3(MAPK/ER)-10.3(K)-340.4(path)-7.6(way.)-344.1(This)-342.6(syst)-8.2(em)-342.6(of)-339.2(intera)-10(ctions)-348.8(results)-347.1(in)-340(som)-7(e)]TJ T* [(neural)-508(functional)-505.2(regulat)-10.7(ions)-502.1(in)-499.4(the)-501.9(brain,)-505.8(such)-501.1(as)-505.3(synapti)-8.1(c)-497.6(plastici)-10.5(ty,)-499.7(neuro)-7.6(tic)-499(grow)-9(th,)-499.7(and)-499.2(neuro)-7.6(nal)]TJ T* [(survival)-272.7(\(C)-8.2(ardona-Gom)-11.2(ez)-272.6(et)-267.8(al.,)-268.6(2)-6.5(002\).)-267.2(Th)-7(e)-264.3(siz)-8(e)-270(o)0(f)-265.3(the)-274.3(trees)-275.1(correspo)-9.1(nding)-268.3(to)-271.7(the)-268.6(down)-7(stream)-273.7(of)-271(MET)-277(and)]TJ T* [(ITGB3)-424(rece)-10.4(ptors)-425.2(increases)-430.8(at)-421.5(each)-423.8(knock-)-8.3(out.)-420.8(Also,)-426.7(the)-422.2(FYN-rel)-9.5(ated)-424.8(downstream)-428.6(path)-7.6(way)-423.4(of)-418.9(CD36)-427.1(is)]TJ T* [(swapped)-338.4(to)-328.7(be)-333.4(down)-7(stream)-336.3(of)-327.9(MET)-333.9(rece)-10.4(ptor,)-332.5(although)-337.8(CD36)-330.4(is)-335.5(not)-329.4(knocke)-8.1(d)-330.8(out.)-329.8(This)-336.9(result)-333.7(implies)-333.1(that)]TJ 0 -1.195 TD [(FYN-r)-9.1(elated)-339.8(pathwa)-9.1(y)-330.8(may)-337.7(be)-339.1(activate)-10.1(d)-330.8(b)0(y)-337.3(several)-341(recepto)-9.7(rs.)]TJ 1.0015 -1.2007 TD [(To)-314.3(further)-323.1(validate)-321.3(the)-319.8(relevan)-9.7(cy)-316.3(of)-316.5(these)-318.6(recep)-11.2(tor)-314.3(molecu)-8.7(les)-315.3(\(EG)-8(FR,)-318.8(ERBB2,)-319.7(IGF)-7.4(1R,)-313.9(CD36,)-325.1(PDGFR,)]TJ -1.0015 -1.2007 TD [(MET,)-317.2(and)-311.4(ITGB3)-8.6(\),)-310.4(we)-314.5(used)-313.3(the)-314.1(TCGA)-317(GBM)-314.5(Gene)-317.8(Ranker)-316.4(\(http://cbi)-11.6(o.mskcc.o)-8.7(rg/tcg)-8.2(a-genera)-11.5(nker/\).)-315(This)]TJ T* [(server)-388.9(combine)-9.5(s)-383.2(available)-392.2(literature)-392.2(inform)-9.1(ation)-386.7(and)-379.7(TCG)-10.7(A)-380.3(data)-390.7(to)-379.9(scor)-8(e)-378.1(indi)-8.6(vidual)-387.5(genes.)-384.5(All)-387.3(selected)]TJ T* [(recepto)-9.7(rs)-249.4(are)-246.8(amo)-7.6(ng)-246.2(highly)-249.1(ranke)-9.4(d)-245.5(genes)-253.3(\(gene)-9.4(s)-246.7(having)-248.1(a)-252.9(score)-249.6(grea)-8.6(ter)-247.8(than)-252.3(2.0\))-249.3(in)-243.3(GBM)-251.9(\(calcul)-12.5(ated)-248.4(scor)-8(es)]TJ T* [(are)-246.8(as)-249.2(follows:)-254.8(EGFR:)-247.6(15.7)-8.4(5,)-245.8(MET:)-246.4(11.75,)-248.5(ERBB)-11.3(2:)-243.3(9.25,)-247.7(PDG)-9.4(FRB:)-247.8(7.25,)-247.7(IGF)-7.4(1R:)-243.1(4)-6.5(.0,)-246.2(ITGB3:)-251.1(3.75,)-247.7(CD36:)]TJ T* [(2.0\),)-335.1(with)-336.9(EGFR)-10.7(,)-330.4(MET)-9.6(,)-330.4(and)-339.8(ERBB2)-336.4(havi)-7.6(ng)-331.6(the)-336.9(highe)-8.4(st)-335.5(ranks)-338.8(in)-334.3(the)-336.9(database)-11.5(.)]TJ 1.0015 -1.2007 TD [(We)-290.4(performed)-298.7(randomizat)-12.6(ion)-289.6(tests)-292.3(to)-288.8(check)-293.7(the)-291.4(reliabili)-9.1(ty)-288.8(of)-288(the)-291.4(output)-288.9(of)-288(the)-291.4(algo)-7.6(rithm.)-288.4(Her)-10(e,)-287.5(terminal)]TJ -1.0015 -1.195 TD [(nodes,)-439.7(their)-434.2(pri)-7(zes,)-434.2(and)-436.6(the)-433.6(para)-8.6(meter)-436.8(set)-440.5(are)-434.6(kept)-434.4(sam)-8.8(e)-429.3(w)0(i)-8.2(t)0(h)-431.1(the)-433.6(o)-6.5(riginal)-438.5(PCSF)-437.9(analysis)-438.7(of)-436(GBM.)-440.1(In)]TJ 0 -1.2007 TD [(addition,)-244.2(number)-239.5(of)-236.8(nodes,)-240.5(edges)-8.6(,)-233.7(and)-243.1(edge)-239.9(costs)-238.4(are)-241.2(the)-240.2(same)-239(as)-237.8(in)-237.6(the)-234.5(o)-6.5(riginal)-239.3(interact)-10.3(ome.)-241.3(Only)-237.4(the)-240.2(edges)]TJ T* [(are)-434.6(reshu)-8.8(fed)-432.8(rando)-7.6(mly)-435.4(within)-432.2(the)-439.3(network.)-437.3(The)-436.4(rando)-7.6(mizati)-8.6(on)-428.3(tes)-8(t)-430.3(i)0(s)-432.3(repeate)-11.5(d)-427.6(ten)-439.3(times)-436.9(on)-428.3(dif)-7(ferent)]TJ T* [(interact)-10.3(omes.)-487.9(Th)-7(e)-486.2(statistics)-495.2(for)-484.2(the)-490.5(aver)-8.6(age)-489.6(of)-487.2(the)-484.8(resu)-8(lting)-490.1(forests)-488.5(are)-491.5(tabulated)-492.8(in)-488(Table)-493.7(S3.)-490.5(These)]TJ T* [(charact)-11.5(eristics)-267(show)-264.3(that)-260.7(rando)-7.6(m)-260.4(PCSFs)-263.4(cont)-7.6(ain)-262.9(many)-264.4(more)-260.7(subt)-7(rees)-260.2(whe)-8(n)-256.8(com)-7.6(pared)-265.4(to)-260.4(the)-262.9(original)-262.8(PCSF,)]TJ T* [(and)-385.3(these)-392.6(subtree)-9.1(s)-383.2(are)-389.1(not)-386.3(structure)-9.7(d)-382(like)-385.9(the)-388.1(origina)-8.9(l)-384.8(trees;)-386.7(mos)-7(t)-384.8(o)0(f)-384.8(the)-388.1(trees)-388.9(in)-385.6(the)-382.4(rando)-7.6(m)-385.6(forest)-8.6(s)-383.2(are)]TJ /F2 1 Tf 0 67.0005 TD [(SIMUL)-9.7(TANE)-9(OUS)-339(RECONST)-12.2(RUCTI)-10.1(ON)-333.3(OF)-340.6(MULTI)-9.5(PLE)-335.9(SIGNA)-9.9(LING)-10248(133)]TJ ET endstream endobj 43 0 obj <> endobj 44 0 obj <>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 45 0 obj <>stream /GS1 gs BT /F1 1 Tf 9.9626 0 0 9.9626 74.0976 715.4644 Tm 0 0 0 rg 0 Tc 0 Tw [()48.5(stri)-8.8(ngy,)45.8()-486.4(composed)-492.4(of)-487.2(nine)-491.3(protei)-8.2(ns)-486.4(at)-489.8(most.)-488.9(Further,)-491.4(rando)-7.6(m)-488(trees)-491.3(are)-491.5(not)-488.8(enriched)-494.2(for)-489.9(a)-486.3(specic)]TJ 0 -1.195 TD [(biol)-8.6(ogical)-281.1(process)-280.7(and)-282.9(none)-278(of)-276.7(the)-280(recepto)-9.7(rs)-277.8(found)-278.9(in)-277.4(the)-274.3(ori)-7(ginal)-278.6(PCSF)-278.6(are)-281(select)-11(ed)-276.5(in)-277.4(the)-280(random)-279.3(PCSFs)-7.4(.)]TJ 0 -1.2007 TD [(Th)-7(e)-332.6(algo)-7.6(rithm)-333.5(uses)-337.3(subst)-9(antiall)-8.6(y)-330.8(more)-340.4(Steiner)-340(nodes)-336.8(to)-334.3(connec)-9.9(t)-333.6(terminal)-342.1(nodes)-342.5(in)-334.3(random)-336.2(case)-9.6(s.)]TJ 1.0015 -1.2007 TD [(We)-364.4(perform)-10.9(ed)-361.8(another)-366.5(rando)-7.6(mizati)-8.6(on)-360(test)-364.4(by)-360(reshufi)-9.3(ng)-360(the)-365.3(nodes)-365.3(in)-362.8(the)-359.7(origina)-8.9(l)-362(interactome)-12.2(.)-358.9(I)0(n)-362(this)]TJ -1.0015 -1.2007 TD [(way)-8(,)-273.5(the)-274.3(degree)-279.4(distribut)-9.7(ion)-272.5(is)-272.9(retained.)-281.1(In)-271(thes)-8.8(e)-270(rando)-7.6(mizati)-8.6(ons,)-277(we)-274.7(retain)-277.4(the)-274.3(same)-278.8(terminal)-279.5(nodes;)-277.8(prizes)]TJ T* [(and)-374(the)-371(p)-6.5(arameter)-376.3(set)-372.2(are)-377.7(kept)-371.8(same)-375.5(with)-371(the)-376.7(original)-376.7(PCSF)-375.3(analysis,)-376.5(but)-374.9(these)-375.5(proteins)-375.1(have)-376.5(now)-370.4(been)]TJ T* [(rando)-7.6(mly)-350(mapped)-347.4(to)-345.7(othe)-7.6(r)-344.2(nodes.)-348.6(The)-345.3(resu)-8(lts)-344.7(show)-349.6(that)-346.1(the)-348.3(characterist)-14.4(ics)-343.8(of)-344.9(the)-348.3(subt)-7(rees)-345.5(in)-345.7(the)-348.3(random)]TJ T* [(PCSFs)-320.3(are)-315.1(simi)-7.6(lar)-316.1(with)-314.1(the)-319.8(previous)-321.1(random)-319.2(case;)-320.4(they)-314.9(are)-315.1()48.5(stringy)-11.1(,)53.8()-315.7(not)-312.3(str)-8.2(uctured)-315.2(and)-317.1(not)-318(enriche)-9.7(d)-313.8(for)]TJ T* [(funct)-10.3(ions.)-388.7(Howeve)-10.3(r,)-384.4(this)-391(time)-389.5(the)-388.1(total)-389.5(numb)-6.6(er)-386.6(of)-384.8(nodes)-393.7(include)-8.7(d)-382(i)0(n)-391.3(the)-388.1(PCSF)-386.7(is)-386.7(n)-6.5(o)0(t)-385.6(a)0(s)-385.8(large)-393.4(as)-385.8(in)-385.6(the)]TJ 0 -1.195 TD [(previ)-10.3(ous)-379.1(rando)-7.6(m)-379.9(case.)-385.6(These)-384(resu)-8(lts)-378.9(show)-383.8(that)-385.9(the)-382.4(real)-381.2(PCSF)-386.7(solution)-385.5(is)-381.1(signicantly)-388.4(differ)-9.4(ent)-382.4(than)-383.2(the)]TJ 0 -1.2007 TD [(rando)-7.6(m)-237.6(solutions.)-239.8(It)-239.6(is)-233.1(partic)-10(ularly)-235.8(im)-7.8(portant)-236.6(that)-238(the)-240.2(recepto)-9.7(rs)-238(found)-233.4(b)-6.5(y)-234.1(the)-234.5(algo)-7.6(rithm)-236.8(run)-237.6(on)-234.8(the)-240.2(GBM)-240.5(data)]TJ T* [(are)-457.4(not)-454.6(selected)-458.1(in)-453.8(the)-456.4(randomizat)-12.6(ions,)-451.2(suppor)-7.7(ting)-452.4(the)-456.4(hypot)-6.6(hesis)-454.6(that)-454.2(these)-455.2(rece)-10.4(ptors)-453.6(are)-451.7(biol)-8.6(ogically)]TJ T* [(rel)-8.8(evant.)]TJ /F2 1 Tf 10.959 0 0 10.959 249.1653 536.1447 Tm [(4.)-501.9(DISCUSSIO)6.7(N)]TJ /F1 1 Tf 9.9626 0 0 9.9626 84.0755 512.277 Tm [(We)-478.2(present)-481.5(a)-474.9(method)-479.3(for)-478.6(simultaneous)-482.2(disc)-8.8(overy)-474.2(of)-475.8(multipl)-8.5(e)-474.9(pathwa)-9.2(ys)-475(by)-473.8(searchi)-10.9(ng)-473.8(for)-472.9()48.5(forest)-11.3(s)52.2()]TJ -1.0015 -1.2007 TD [(consi)-9.6(sting)-295.1(of)-299.4(multiple)-301.3(trees.)-298.2(We)-301.8(are)-298.1(able)-299.6(to)-294.5(solve)-299.8(this)-294.3(problem)-299.9(efci)-11.3(ently,)-296(even)-302.5(for)-296.5(large)-296.7(huma)-8.4(n)-291(networ)-9.3(ks,)]TJ T* [(by)-251.9(a)-247.2(simple)-249.9(modica)-8.7(tion)-247.6(of)-248.2(the)-251.5(previous)-8.1(ly)-249(published)-254.4(message)-10.9(-passing)-254(solution)-248.9(for)-250.9(the)-245.8(Steiner)-254.6(tree)-250.4(probl)-8.6(em.)]TJ T* [(When)-462.6(applied)-458.3(to)-453.8(the)-450.7(phero)-7.6(mone)-457.9(response)-457.9(data)-458.9(on)-451.1(the)-456.4(directed)-457.1(y)-6.5(east)-454.4(interact)-10.3(ome,)-457.5(the)-450.7(PCSF)-460.7(approach)]TJ T* [(reve)-8.6(als)-360.8(several)-363.7(para)-8.6(llel)-360.2(pathwa)-9.1(ys)-355.5(affect)-11(ed)-356.1(by)-360(yeast)-364.2(pheromon)-7.7(e.)-361.4(Some)-360.4(of)-356.3(thes)-8.8(e)-355.4(para)-8.6(llel)-360.2(pathwa)-9.2(ys)-355.5(cont)-7.6(ain)]TJ T* [(mul)-8.6(tiple,)-310.2(coherent)-10.5(ly)-305.9(acting)-315.3(processe)-10.1(s)-303.6(such)-313.3(as)-306.1(ph)-7.2(eromone)-310.3(resp)-8(onse)-307.6(and)-311.4(the)-308.4(CDC)-10(28)-303.1(assoc)-9.8(iated)-314.5(pathway,)-311.9(or)]TJ T* [(tra)-8.8(nsport)-283.6(and)-288.6(transcr)-11.1(iptional)-292.1(activity)-288.2(of)-288(PHO4.)-289.3(Other)-8.6(s)-280.8(cont)-7.6(ain)-285.7(only)-284.7(o)-6.5(n)0(e)-282.2(proce)-9.4(ss,)-283.1(such)-290.6(as)-283.3(act)-8.6(in)-283.1(organ)-7.6(ization)]TJ T* [(or)-310.8(prot)-7.8(ein)-308.4(fol)-7(ding.)-313.5(Independen)-9.3(tly)-309.4(from)-317.8(the)-308.4(phero)-7.6(mone)-315.7(response)-315.6(networ)-9.3(k,)-308.4(we)-314.5(also)-310.4(show)-315.5(that)-312(this)-317.1(approach)]TJ 0 -1.195 TD [(can)-478.2(identify)-473.4(regions)-479.7(of)-470.1(the)-473.5(yeast)-472.3(intera)-10(ctome)-474.6(enriche)-9.7(d)-467.4(i)0(n)-470.9(vario)-10.3(us)-469.3(biologi)-7.9(cal)-469.6(proce)-9.4(sses)-475(using)-468.7(o)-6.5(nly)-471.7(the)]TJ 0 -1.2007 TD [(connec)-9.9(tivity)-340(informat)-9.5(ion)-335.1(\(see)-339.8(Suppleme)-9.5(ntary)-334.7(Mat)-8.8(erial\).)]TJ 1.0015 -1.2007 TD [(The)-351(advant)-10.9(ages)-349.2(of)-350.6(the)-354(forest)-350(appro)-7.6(ach)-353(are)-349.3(mos)-7(t)-345(appar)-9.4(ent)-348.3(whe)-8(n)-347.9(used)-353.2(to)-345.7(stud)-7(y)-347.9(mammal)-10.1(ian)-348.3(cells,)-355.9(which)]TJ -1.0015 -1.2007 TD [(resp)-8(ond)-235.6(to)-237.6(a)-235.9(large)-239.7(number)-239.5(of)-236.8(hormones)-8.9(,)-233.7(growth)-240.9(factor)-9.2(s,)-235.6(and)-237.4(cytokine)-9.5(s.)-235.7(Applying)-243.2(this)-237.4(approach)-241.1(to)-237.6(proteom)-9.7(ic)]TJ T* [(data)-271.2(from)-272.3(a)-264.3(mode)-8.4(l)-265.3(o)0(f)-265.3(GBM)-269(resu)-8(lts)-265.1(in)-266.1(a)-270(forest)-270.3(composed)-270.5(o)-6.5(f)-264.5(several)-272.7(subtree)-9.2(s,)-264.1(each)-270.2(of)-271(which)-268.4(is)-267.3(rooted)-272.9(from)-266.6(a)]TJ T* [(rece)-10.4(ptor)-423.2(molecule.)-424.9(Th)-7(e)-418(PCSF)-420.8(algo)-7.6(rithm)-424.6(is)-420.9(able)-419.1(to)-419.7(sel)-8(ect)-418.3(rece)-10.4(ptors)-419.5(relevan)-9.7(t)-418.9(t)0(o)-419.7(GBM)-428.3(from)-420.3(hundre)-8.3(ds)-418.1(of)]TJ T* [(mol)-8.6(ecules)-372.4(in)-368.5(the)-371(human)-367.6(rece)-10.4(ptome.)-370.8(The)-373.8(solution)-374.1(reveals)-375.1(several)-375.1(known)-371.9(pathwa)-9.1(ys)-366.9(and)-368.3(som)-7(e)-366.7(unexpe)-8.1(cted)]TJ T* [(new)-247(ones.)-239.7(EGFR)-10.7(,)-233.7(ERBB)-11.3(2,)-240.2(IGF1R)-8(,)-233.7(and)-243.1(CD36)-245(are)-241.2(start)-8.6(ing)-238.4(nodes)-245.8(of)-236.8(the)-240.2(largest)-245.2(subt)-7(rees)-243.1(in)-237.6(the)-245.8(PCSF.)-239.1(Th)-7(is)-238.8(set)]TJ 0 -1.195 TD [(of)-271(recepto)-9.7(r)-264.5(molecu)-8.7(les)-264.1(was)-271(select)-11(ed)-265.1(by)-263.3(the)-268.6(algo)-7.6(rithm)-270.9(among)-270.9(hundreds)-272.8(of)-265.3(recepto)-9.7(rs,)-266.8(and)-265.8(the)-268.6(lite)-7.4(rature)-270.9(search)]TJ 0 -1.2007 TD [(show)-8.2(s)-332(that)-340.4(each)-338.5(of)-333.6(the)-336.9(select)-11(ed)-333.4(recepto)-9.7(rs)-334.7(is)-335.5(clinical)-11.1(ly)-334.3(relevant)-337.6(to)-340(GBM.)]TJ 1.0015 -1.2007 TD [(To)-308.6(nd)-308.8(addi)-7.6(tional)-310.6(recepto)-9.7(rs)-306.3(whose)-312.3(down)-7(stream)-313.5(signaling)-314(pathwa)-9.2(ys)-304.3(overlap)-315.3(with)-308.4(the)-308.4(sel)-8(ected)-313.5(receptors,)]TJ -1.0015 -1.2007 TD [(we)-251.9(used)-250.7(an)-248(itera)-9.2(tive)-249.4(approach)-252.4(that)-249.4(can)-250.6(be)-248(thoug)-6.6(ht)-249(of)-248.2(as)-249.2(an)]TJ /F5 1 Tf 23.4508 0 TD [(in)-243.3(silic)-9.4(o)]TJ /F1 1 Tf 3.4542 0 TD [(knock-o)-9.1(ut)-243.3(exper)-9.4(iment.)-248.3(In)-248.2(this)-248.8(anal)-9.4(ysis,)-247.6(a)]TJ -26.9049 -1.2007 TD [(sel)-8(ected)-239.6(rece)-10.4(ptor)-241.1(molecule)-242.4(and)-243.1(all)-237.2(it)-7.1(s)-235.3(interact)-10.3(ions)-240.3(are)-241.1(removed)-247.7(from)-238.2(the)-240.2(intera)-10(ctome,)-241.7(and)-243.1(PCSF)-238.7(algo)-7.6(rithm)-242.5(is)]TJ T* [(appl)-7.6(ied)-234.5(to)-237.6(the)-234.5(rem)-9.6(aining)-239.5(network.)-238.1(Th)-7(ese)-234.7(cal)-8.6(culations)-241.8(reveale)-11.5(d)-234.1(the)-234.5(roles)-239.2(of)-236.8(PDGF)-9.3(R,)-233.5(MET,)-237.6(and)-237.4(ITG)-8(B3,)-234.2(all)-237.2(of)]TJ T* [(whi)-9(ch)-333.4(have)-336.7(been)-342.4(previous)-8.1(ly)-334.3(linked)-336.2(to)-334.3(GBM.)]TJ 1.0015 -1.2007 TD [(Our)-452.1(method)-450.8(can)-449.7(be)-447.2(efcienly)-451.4(utilize)-8.6(d)-444.6(t)0(o)-448.2(reco)-8.6(nstruct)-448.3(networ)-9.3(ks)-446.6(that)-448.5(are)-446(enri)-9.6(ched)-450.5(in)-442.5(functi)-8.2(onally)-450.1(and)]TJ -1.0015 -1.195 TD [(clini)-8.2(cally)-331.6(relevan)-9.7(t)-322.2(protei)-8.2(ns.)-327.5(Further,)-332.1(the)-325.5(algo)-7.6(rithm)-327.8(is)-324.2(exib)-7.6(le,)-325.1(and)-328.4(can)-330.2(be)-327.7(modied)-331.3(for)-330.6(other)-329(types)-328.2(of)-327.9(data)]TJ 0 -1.2007 TD [(such)-341.8(as)-334.6(protei)-8.2(nsmal)-8.1(l)-333.6(molecule)-339.2(inhibi)-7.2(tor)-337.1(interact)-10.3(ions)-337.1(and)-334.1(protei)-8.2(nmeta)-8.7(bolite)-339(interactions)-11.7(.)]TJ /F2 1 Tf 10.959 0 0 10.959 228.5291 177.5054 Tm -.0003 Tc (ACKNOWLEDGMENTS)Tj /F1 1 Tf 9.9626 0 0 9.9626 84.0755 153.5811 Tm 0 Tc [(We)-381.4(th)18.5(an)19.4(k)-365(D)0(r)15.3(.)-364.6(Sa)14.5(ra)-358.1(Go)17.3(sl)17.3(in)18.5(e)-366.7(f)0(r)17.3(o)0(m)-357.9(M)0(I)17.3(T)-364.8(an)13.8(d)-365(D)0(r)21(.)-370.3(O)12.4(z)0(n)13.8(u)0(r)-356.3(T)10.8(as)12.6(t)13.5(a)0(n)-361.8(f)0(r)17.3(o)0(m)-357.9(M)0(i)22.2(c)0(r)17.5(o)0(s)14.4(o)0(f)19.3(t)-367.7(R)11.6(e)0(s)12.6(e)0(a)17.7(r)0(c)17.5(h)-365(fo)19.3(r)-366.9(t)0(h)18.5(e)0(i)16.7(r)-366.9(cr)17.5(it)21.4(ic)16.7(al)]TJ -1.0015 -1.2007 TD [(re)17.5(ad)13.8(in)18.5(g)-319.4(a)0(n)13.8(d)-319.4(fr)17.3(ui)18.5(t)13.5(f)0(u)13.6(l)-316.5(co)13.8(mm)19.9(en)13.8(t)13.5(s)0(.)-315.3(T)10.8(hi)18.5(s)-320.6(w)0(o)17.3(r)0(k)-316.5(i)13.5(s)-320.6(s)0(u)14.3(p)0(p)21.2(o)0(r)19.3(t)0(e)16.7(d)-325.1(by)-308.8(NI)15.3(H)-323.4(g)0(r)19.3(a)0(n)19.4(t)0(s)-312.8(U)0(5)17.3(4)0(C)16.5(A)0(1)17.3(1)0(2)15.5(9)0(6)21.2(7)0(,)-314.1(R)11.6(01)15.5(GM)15.3(08)21.2(99)15.5(03)21.2(,)-324.7(a)0(n)19.4(d)]TJ 0 -1.195 TD [(In)13.6(st)17.3(i)13.5(t)0(u)18.5(t)0(e)-393(f)0(o)13.6(r)-401.1(C)11.6(o)0(l)18.5(l)0(a)16.7(b)0(o)15.5(r)0(a)17.5(t)13.5(iv)12.8(e)-400.9(B)11.6(io)18.5(te)16.7(ch)13.8(no)21.2(lo)18.5(gi)18.5(es)-397.2(t)13.5(h)0(r)13.6(o)0(u)21.2(g)0(h)-394.2(g)0(r)19.3(a)0(n)19.4(t)-401.9(W9)13(11)21.2(NF)12.4(-)14.3(0)0(9)15.5(-)0(0)19.2(0)0(0)15.5(1)-399.1(fr)17.3(om)-392(th)18.5(e)-406.6(U)12.4(S)-404(A)0(r)15.3(m)12.8(y)-404.8(R)11.6(es)12.6(ea)17.7(rc)17.5(h)]TJ 0 -1.2007 TD [(Of)15.3(c)14.5(e)-326.9(\()14.3(th)12.8(e)-321.2(c)0(o)13.8(n)0(t)18.5(e)0(n)19.4(t)-327.9(of)-316.5(t)13.5(h)0(e)-322(i)13.5(nf)19.3(or)13.6(ma)15.9(t)13.5(i)0(o)18.5(n)-325.1(do)15.5(es)-317.5(no)21.2(t)-327.9(n)0(e)19.4(c)0(e)12(s)0(s)18.9(a)0(r)17.5(i)0(l)21.4(y)-325.1(re)17.5(e)14.5(ct)-319.1(t)13.5(h)0(e)-316.3(p)0(o)15.5(s)0(i)17.3(t)0(i)21.4(o)0(n)-320.2(o)0(r)-316.5(t)13.5(he)-322(po)21.2(li)15.7(cy)-316.3(of)-316.5(t)13.5(h)0(e)-322(G)12.4(ov)15.5(er)17.5(n-)]TJ T* [(me)15.9(nt)18.5(,)-284.9(a)0(n)19.4(d)-285.3(no)-274.7(of)19.3()11.4(c)0(i)16.7(a)0(l)-273.5(e)0(n)13.8(d)0(o)21.2(r)0(s)18.1(e)0(m)15.9(e)0(n)13.8(t)-282.4(sh)20(ou)15.5(l)13.5(d)-285.3(be)-276.5(i)13.5(n)0(f)13.6(e)0(r)17.5(r)0(e)17.5(d)0(\))-271(a)0(n)13.8(d)-279.6(us)14.4(ed)-270.8(co)13.8(m)12.8(p)0(u)15.5(t)0(i)15.7(n)0(g)-269(r)0(e)17.5(s)0(o)14.3(u)0(r)19.3(c)0(e)17.7(s)-286.5(fu)19.3(nd)21.2(ed)-276.5(by)-274.7(th)18.5(e)-281.4(N)0(a)15.5(t)0(i)15.7(o)0(n)21.2(a)0(l)]TJ T* [(Sc)14.5(ie)16.7(nc)19.4(e)-400.9(F)0(o)16.3(u)0(n)15.5(d)0(a)19.4(t)0(i)15.7(o)0(n)-388.5(u)0(n)15.5(d)0(e)19.4(r)-401.1(Aw)13.4(ar)17.5(d)-399.1(N)0(o)17.3(.)-398.7(DB)12.6(1-)19.3(08)15.5(21)21.2(39)15.5(1.)-388.1(E.)16.1(F.)-393(re)17.5(ce)17.7(iv)18.5(es)-391.5(su)14.4(pp)21.2(or)13.6(t)-396.2(f)0(r)17.3(o)0(m)-392(t)0(h)18.5(e)-406.6(E)10.8(u)0(g)15.5(e)0(n)19.4(e)-400.9(Be)14.7(ll)-388.3(Ca)14.7(re)17.5(er)]TJ T* [(De)15.5(ve)13.8(l)13.5(o)0(p)15.5(m)0(e)15.9(n)0(t)-374.2(C)0(h)16.5(a)0(i)16.7(r)0(.)-378.7(R)11.6(.Z)16.1(.)-381.6(a)0(c)12(k)0(n)21.2(o)0(w)17.3(l)0(e)16.7(d)0(g)15.5(e)0(s)-374.4(t)0(h)18.5(e)-389.5(E)10.8(R)0(C)-380.8(g)0(r)19.3(a)0(n)19.4(t)-384.8(OP)18.1(TI)13.8(NF)-374.6(26)15.5(79)21.2(15)15.5(.)-387.3(T)10.8(he)-378.9(su)20(pp)15.5(or)19.3(t)-384.8(f)0(r)17.3(o)0(m)-374.9(t)0(h)18.5(e)-383.8(EC)-381.6(gr)19.3(an)19.4(t)]TJ T* [(ST)16.5(AM)15.3(IN)15.3(A)-323.4(2)0(6)15.5(5)0(4)21.2(9)0(6)-320.2(i)13.5(s)-326.3(a)0(l)16.7(s)0(o)-315.7(a)0(c)17.7(k)0(n)21.2(o)0(w)11.6(l)13.5(ed)13.8(ge)19.4(d)-325.1(b)0(y)-314.5(A)0(.)17.7(B)0(.)-313.1(a)0(n)13.8(d)-325.1(R)11.6(.)0(Z)16.1(.)]TJ /F2 1 Tf 0 67.0005 TD [(13)-7.2(4)]TJ 34.5644 0 TD [(TUNCBA)-12.7(G)-334.4(E)0(T)-335.3(AL.)]TJ ET endstream endobj 46 0 obj <> endobj 47 0 obj <>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 48 0 obj <>stream /GS1 gs BT /F2 1 Tf 10.959 0 0 10.959 251.2062 714.7841 Tm 0 0 0 rg 0 Tc 0 Tw [(DISCLOSURE)-328.8(STATEMENT)]TJ /F1 1 Tf 9.9626 0 0 9.9626 117.5811 690.9164 Tm [(The)-333.9(auth)-7.6(ors)-335.5(declare)-341.6(that)-334.7(n)-6.5(o)-330.8(com)-7.6(peting)-336.2(nanci)-10.1(al)-330.4(int)-7.8(erests)-339.6(exist.)]TJ /F2 1 Tf 10.959 0 0 10.959 286.0724 655.0298 Tm (REFERENCES)Tj /F1 1 Tf 8.9663 0 0 8.9663 107.6031 631.1053 Tm [(Adams,)-295.5(T.E.,)-291.9(McKern,)-296(N.M.,)-296.3(Ward,)-292.4(C.W.)-296(2004.)-291.8(Signalling)-290.4(by)-296.2(the)-289.5(type)-295.3(1)-290.4(insulin-like)-298.7(growth)-291.5(factor)-295.7(receptor:)-294.3(interplay)]TJ .999 -1.2203 TD [(with)-331.9(the)-333.8(epidermal)-339.5(growth)-335.8(factor)-333.6(receptor.)]TJ /F5 1 Tf 17.7484 0 TD [(Growth)-332.8(Factors)]TJ /F1 1 Tf 6.8287 0 TD [(22,)-337.1(8995.)]TJ -25.5762 -1.2203 TD [(Agren,)-306(M.,)-303.2(Kogerman,)-304.1(P.,)-301.1(Kleman,)-306.5(M.I.,)-301.9(et)-309(al.)-299.2(2004.)-304.5(Expression)-303.5(of)-305.1(the)-302.1(PTCH1)-307.5(tumor)-304.9(suppressor)-303.5(gene)-306.4(is)-301.4(regulated)-304.4(by)]TJ .999 -1.2266 TD [(alternative)-339.1(promoters)-334.4(and)-336.1(a)-330.7(single)-337.5(functional)-330.8(Gli-binding)-339.1(site.)]TJ /F5 1 Tf 25.6647 0 TD (Gene)Tj /F1 1 Tf 2.447 0 TD [(330,)-330.2(10114.)]TJ -29.1107 -1.2203 TD [(Akavia,)-277.7(U.D.,)-279.9(Litvin,)-277.4(O.,)-280.5(Kim,)-277.9(J.,)-278.4(et)-277.3(al.)-280.3(2010.)-279.2(An)-274.2(integrated)-282.6(approach)-284.2(to)-274.9(uncover)-282.2(drivers)-275(of)-279.8(cancer.)]TJ /F5 1 Tf 40.2706 0 TD (Cell)Tj /F1 1 Tf 1.9538 0 TD [(143,)-273.3(100517.)]TJ -42.2244 -1.2203 TD [(Alam,)-305.1(N.,)-299.5(Goel,)-301.6(H.L.,)-308.1(Zarif,)-302.8(M.J.,)-300.5(et)-302.6(al.)-305.6(2007.)-298.1(The)-304.3(integrin-growth)-306.8(factor)-302(receptor)-303.4(duet.)]TJ /F5 1 Tf 35.9078 0 TD [(J.)-302(Cell.)-307(Physiol.)]TJ /F1 1 Tf 6.7908 0 TD [(213,)-305(64953.)]TJ -42.6986 -1.2267 TD [(Baetz,)-244.1(K.,)-242.6(Moffat,)-246.3(J.,)-240.5(Haynes,)-249.6(J.,)-240.5(et)-245.7(al.)-242.3(2001.)-241.2(Transcriptional)-249.9(coregulation)-243.7(by)-245.6(the)-238.9(cell)-244.9(integrity)-244.3(mitogen-activated)-251.3(protein)]TJ .999 -1.2203 TD [(kinase)-335.9(Slt2)-333.5(and)-336.1(the)-333.8(cell)-333.4(cycle)-337.6(regulator)-336.2(Swi4.)]TJ /F5 1 Tf 19.0256 0 TD [(Mol.)-336.4(Cell.)-332.3(Biol.)]TJ /F1 1 Tf 6.7213 0 TD [(21,)-330.7(651528.)]TJ -26.7459 -1.2203 TD [(Bailly-Bechet,)-299.9(M.,)-290.6(Borgs,)-293.5(C.,)-294.6(Braunstein,)-297.6(A.,)-293.2(et)-296.3(al.)-292.9(2010a.)-293.8(Finding)-294.1(undetected)-297.4(protein)-294.2(associations)-295.2(in)-293.9(cell)-295.5(signaling)-295.8(by)]TJ .999 -1.2203 TD [(belief)-335(propagation.)]TJ /F5 1 Tf 7.9985 0 TD [(Proc.)-333.2(Natl.)-336.2(Acad.)-332(Sci.)-336.7(U.S.A.)]TJ /F1 1 Tf 12.2159 0 TD [(108,)-336.6(8827.)]TJ -21.2134 -1.2267 TD [(Bailly-Bechet,)-337.9(M.,)-334.8(Bradde,)-334.6(S.,)-332.7(Braunstein,)-335.6(A.,)-337.4(et)-334.2(al.)-330.8(2009.)-336.1(Clustering)-334.3(with)-331.9(shallow)-334(trees.)]TJ /F5 1 Tf 36.7298 0 TD [(J.)-333.6(Stat.)-337.8(Mech.)]TJ /F1 1 Tf 5.9941 0 TD (P12010.)Tj -42.7239 -1.2203 TD [(Bailly-Bechet,)-312.6(M.,)-309.5(Braunstein,)-310.3(A.,)-312.1(Pagnani,)-310.4(A.,)-305.8(et)-309(al.)-311.9(2010b.)-310.3(Inference)-310.3(of)-311.5(sparse)-310.4(combinatorial-control)-313.1(networks)-306.8(from)]TJ .999 -1.2203 TD [(gene-expression)-336.4(data:)-339.2(a)-330.7(message)-338.5(passing)-334.2(approach.)]TJ /F5 1 Tf 21.2387 0 TD [(BMC)-334(Bioinformatics)]TJ /F1 1 Tf 8.7383 0 TD [(11,)-330.7(355.)]TJ -30.9759 -1.2266 TD [(Bayati,)-308.4(M.,)-309.5(Borgs,)-306.2(C.,)-307.2(Braunstein,)-316.6(A.,)-305.8(et)-309(al.)-305.6(2008.)-310.8(Statistical)-310.3(mechanics)-311.2(of)-311.4(steiner)-310.4(trees.)]TJ /F5 1 Tf 36.0027 0 TD [(Phys.)-307.9(Rev.)-309.6(Lett.)]TJ /F1 1 Tf 6.6896 0 TD [(101,)-311.3(037208.)]TJ -42.6923 -1.2203 TD [(Ben-Shlomo,)-336.4(I.,)-330.4(Yu)-331.1(Hsu,)-334.7(S.,)-332.7(Rauch,)-332.5(R.,)-332.5(et)-334.3(al.)-337.2(2003.)-329.8(Signaling)-337.5(receptome:)-335.1(a)-330.7(genomic)-337.8(and)-329.7(evolutionary)-336.1(perspective)-338.6(of)]TJ .999 -1.2203 TD [(plasma)-333.1(membrane)-341.8(receptors)-335.7(involved)-329(in)-338.2(signal)-331.2(transduction.)]TJ /F5 1 Tf 24.9881 0 TD [(Sci.)-330.4(STKE)]TJ /F1 1 Tf 4.4766 0 TD [(2003,)-329.8(RE9.)]TJ -30.4638 -1.2266 TD [(Bhoite,)-344(L.T.,)-348.8(Allen,)-343(J.M.,)-344.8(Garcia,)-346(E.,)-346.6(et)-346.9(al.)-343.5(2002.)-342.4(Mutations)-347.1(in)-344.5(the)-346.4(pho2)-345.8(\(bas2\))-341(transcription)-349.8(factor)-346.3(that)-343.6(differentially)]TJ .999 -1.2203 TD [(affect)-336(activation)-334.6(with)-338.2(its)-330.2(partner)-339.4(proteins)-332.8(bas1,)-333.4(pho4,)-336.1(and)-329.7(swi5.)]TJ /F5 1 Tf 26.3096 0 TD [(J.)-333.6(Biol.)-331.3(Chem.)]TJ /F1 1 Tf 6.2028 0 TD [(277,)-336.6(376128.)]TJ -33.5114 -1.2203 TD [(Breitkreutz,)-361.9(A.,)-362.7(Choi,)-363.8(H.,)-356.4(Sharom,)-367.5(J.R.,)-361.4(et)-359.5(al.)-362.5(2010.)-361.4(A)-356.9(global)-361.6(protein)-363.7(kinase)-361.2(and)-361.4(phosphatase)-368.7(interaction)-362(network)-363(in)]TJ .999 -1.2203 TD (yeast.)Tj /F5 1 Tf 2.643 0 TD (Science)Tj /F1 1 Tf 3.408 0 TD [(328,)-330.2(10436.)]TJ -7.05 -1.2266 TD [(Buehrer,)-374.7(B.M.,)-367.3(and)-374(Errede,)-370.2(B.)-373.9(1997.)-367.7(Coordination)-376.4(of)-368.4(the)-371.7(mating)-371.5(and)-374(cell)-371.3(integrity)-370.8(mitogen-activated)-377.8(protein)-370.1(kinase)]TJ .999 -1.2203 TD [(pathways)-338.2(in)-331.8(Saccharomyces)-336.5(cerevisiae.)]TJ /F5 1 Tf 16.4016 0 TD [(Mol.)-336.4(Cell.)-332.3(Biol.)]TJ /F1 1 Tf 6.7213 0 TD [(17,)-330.7(651725.)]TJ -24.1219 -1.2203 TD [(Cancer)-277.2(Genome)-280.6(Atlas)-278.1(Research)-286.2(Network.)-280.7(2008.)-272.9(Comprehensive)-282.5(genomic)-280.9(characterization)-283.3(denes)-279.9(human)-275.4(glioblastoma)]TJ .999 -1.2266 TD [(genes)-332.4(and)-336.1(core)-334.3(pathways.)]TJ /F5 1 Tf 10.8185 0 TD (Nature)Tj /F1 1 Tf 3.1172 0 TD [(455,)-330.2(10618.)]TJ -14.9347 -1.2203 TD [(Cardona-Gomez,)-244.3(G.P.,)-237.3(Mendez,)-235.6(P.,)-237.9(DonCarlos,)-244.4(L.L.,)-235(et)-239.4(al.)-236(2002.)-241.2(Interactions)-241.2(of)-235.6(estrogen)-236.4(and)-241.2(insulin-like)-241.8(growth)-234.6(factor-)]TJ .999 -1.2203 TD [(I)-330.9(i)0(n)-338.2(the)-333.8(brain:)-332.6(molecular)-339.5(mechanisms)-332(and)-336.1(functional)-337.1(implications.)]TJ /F5 1 Tf 27.4035 0 TD [(J.)-333.6(Steroid)-330.7(Biochem.)-340.3(Mol.)-330.1(Biol.)]TJ /F1 1 Tf 12.8102 0 TD [(83,)-330.7(2117.)]TJ -41.2127 -1.2266 TD [(Chakravarti,)-307.3(A.,)-305.8(Loefer,)-311.4(J.S.,)-304.7(and)-304.5(Dyson,)-308.5(N.J.)-306.5(2002.)-304.5(Insulin-like)-309.9(growth)-304.2(factor)-308.3(receptor)-309.8(I)-305.6(mediates)-313.3(resistance)-308.7(to)-306.5(anti-)]TJ .999 -1.2203 TD [(epidermal)-459.6(growth)-455.9(factor)-453.7(receptor)-461.5(therapy)-457(in)-452(primary)-460.7(human)-452.4(glioblastoma)-456.1(cells)-460.5(through)-452.1(continued)-457.4(activation)-461.1(of)]TJ T* [(phosphoinositide)-335.5(3-kinase)-337.5(signaling.)]TJ /F5 1 Tf 15.1623 0 TD [(Cancer)-336.6(Res.)]TJ /F1 1 Tf 5.3112 0 TD [(62,)-337.1(2007.)]TJ -21.4726 -1.2266 TD [(Chekuri,)-297.8(C.,)-300.9(Ene,)-300.9(A.,)-299.5(and)-298.1(Korula)-300.3(N.)-296.6(2010.)-298.1(Prize-Collecting)-302.4(Steiner)-301.5(Tree)-302.5(and)-298.1(Forest)-296.7(in)-300.2(Planar)-298(Graphs.)]TJ /F5 1 Tf 41.5858 0 TD [(Data)-302.5(Structures)]TJ -40.5868 -1.2203 TD [(and)-333.6(Algorithms)]TJ /F1 1 Tf 6.2787 0 TD (.)Tj -7.2777 -1.2203 TD [(Clarke,)-452.4(I.D.,)-450(and)-449.9(Dirks,)-454.2(P.B.)-450.8(2003.)-449.9(A)-445.4(human)-452.4(brain)-449.2(tumor-derived)-454.2(PDGFR-alpha)-457.2(deletion)-449.3(mutant)-453.7(is)-446.8(transforming.)]TJ /F5 1 Tf .999 -1.2203 TD (Oncogene)Tj /F1 1 Tf 4.3944 0 TD [(22,)-337.1(72233.)]TJ -5.3934 -1.2266 TD [(Dai,)-365.3(C.,)-364.2(Celestino,)-369.1(J.C.,)-361.4(Okada,)-362.7(Y.,)-369.1(et)-365.9(al.)-362.5(2001.)-361.4(PDGF)-368.5(autocrine)-361.3(stimulation)-369.6(dedifferentiates)-370.8(cultured)-365.7(astrocytes)-363.1(and)]TJ .999 -1.2203 TD [(induces)-329.1(oligodendrogliomas)-323(and)-323.4(oligoastrocytomas)-333.4(from)-322.9(neural)-324.7(progenitors)-327.6(and)-323.4(astrocytes)-331.5(in)-325.5(vivo.)]TJ /F5 1 Tf 40.7385 0 TD [(Genes)-329.4(Dev.)]TJ /F1 1 Tf 5.0141 0 TD (15,)Tj -45.7526 -1.2203 TD (191325.)Tj -.999 -1.2266 TD [(Dittrich,)-345.9(M.T.,)-349.7(Klau,)-352.1(G.W.,)-348.1(Rosenwald,)-351.7(A.,)-343.8(et)-346.9(al.)-349.8(2008.)-348.7(Identifying)-349.4(functional)-349.7(modules)-349.2(in)-344.5(protein-protein)-350.2(interaction)]TJ .999 -1.2203 TD [(networks:)-335.6(an)-336.6(integrated)-333.2(exact)-337.6(approach.)]TJ /F5 1 Tf 16.6356 0 TD (Bioinformatics)Tj /F1 1 Tf 6.285 0 TD [(24,)-337.1(i22331.)]TJ -23.9196 -1.2203 TD [(Friedman,)-335.1(N.)-334.5(2004.)-329.8(Inferring)-334.9(cellular)-340.5(networks)-332.1(using)-337.9(probabilistic)-332.2(graphical)-336(models.)]TJ /F5 1 Tf 34.9594 0 TD (Science)Tj /F1 1 Tf 3.408 0 TD [(303,)-330.2(799805.)]TJ -38.3674 -1.2266 TD [(Garcia,)-390.2(R.,)-383.1(Bermejo,)-392.3(C.,)-389.4(Grau,)-382.3(C.,)-389.4(et)-384.8(al.)-387.8(2004.)-386.7(The)-386.5(global)-393.2(transcriptional)-386.8(response)-391.6(to)-382.4(transient)-389.3(cell)-390.3(wall)-391.2(damage)-387.2(in)]TJ .999 -1.2203 TD [(Saccharomyces)-317.6(cerevisiae)-316.2(and)-310.8(its)-311.3(regulation)-311.8(by)-308.8(the)-308.5(cell)-314.4(integrity)-313.9(signaling)-308.5(pathway.)]TJ /F5 1 Tf 34.5547 0 TD [(J.)-308.3(Biol.)-312.3(Chem.)]TJ /F1 1 Tf 6.1395 0 TD [(279,)-305(1518395.)]TJ -41.6933 -1.2203 TD [(Gruhler,)-305.3(A.,)-299.5(Olsen,)-302.3(J.V.,)-303.1(Mohammed,)-308.8(S.,)-301.1(et)-302.6(al.)-299.2(2005.)-304.5(Quantitative)-303(phosphoproteomics)-304(applied)-306.6(to)-300.2(the)-302.2(yeast)-304.8(pheromone)]TJ .999 -1.2203 TD [(signaling)-333.7(pathway.)]TJ /F5 1 Tf 7.9858 0 TD [(Mol.)-336.4(Cell.)-332.3(Proteomics)]TJ /F1 1 Tf 9.3579 0 TD [(4,)-331.2(31027.)]TJ -18.3428 -1.2266 TD [(Gupta,)-256.8(A.,)-261.6(Konemann,)-263.6(J.,)-259.5(Leonardi,)-256.9(S.,)-263.2(et)-258.4(al.)-261.3(2007.)-260.2(An)-255.2(efcient)-265.5(cost-sharing)-261.2(mechanism)-261.7(for)-256.7(the)-264.2(prize-collecting)-263.5(Steiner)]TJ .999 -1.2203 TD [(forest)-332.4(problem.)]TJ /F5 1 Tf 6.5379 0 TD [(SODA)-339.6(07)-329.9(Proceedings)-336.9(of)-338.2(the)-333.8(eighteenth)-330.6(annual)-336.2(ACM-SIAM)-332.4(symposium)-339.8(on)-334.1(Discrete)-333.2(algorithms)]TJ /F1 1 Tf 39.436 0 TD (.)Tj -46.9729 -1.2203 TD [(Huang,)-417.2(P.H.,)-420.7(Mukasa,)-417.7(A.,)-419.6(Bonavia,)-417.7(R.,)-421.1(et)-416.4(al.)-419.4(2007.)-418.3(Quantitative)-423.1(analysis)-422.3(of)-412.6(EGFRvIII)-421.3(cellular)-422.7(signaling)-422.3(networks)]TJ .999 -1.2266 TD [(reveals)-334.1(a)-337(combinatorial)-339.3(therapeutic)-335.1(strategy)-335.2(for)-332.5(glioblastoma.)]TJ /F5 1 Tf 25.456 0 TD [(Proc.)-333.2(Natl.)-336.2(Acad.)-332(Sci.)-336.7(U.S.A)]TJ /F1 1 Tf 11.9629 0 TD [(104,)-336.6(1286772.)]TJ -38.418 -1.2203 TD [(Huang,)-512(S.S.,)-517.1(and)-513.1(Fraenkel,)-517.3(E.)-514.4(2009.)-513.1(Integrating)-516.2(proteomic,)-517(transcriptional,)-522.5(and)-513.1(interactome)-515.7(data)-519.1(reveals)-517.5(hidden)]TJ .999 -1.2203 TD [(components)-337.5(of)-330.4(signaling)-333.7(and)-336.1(regulatory)-335.7(networks.)]TJ /F5 1 Tf 20.8403 0 TD [(Sci.)-336.7(Signal.)]TJ /F1 1 Tf 4.9572 0 TD [(2,)-331.2(ra40.)]TJ -26.7965 -1.2267 TD [(Issel-Tarver,)-356.1(L.,)-346.6(Christie,)-357.1(K.R.,)-350.9(Dolinski,)-350.7(K.,)-350.1(et)-353.2(al.)-349.8(2002.)-348.7(Saccharomyces)-355.5(Genome)-356.5(Database.)]TJ /F5 1 Tf 38.4054 0 TD [(Methods)-354.1(Enzymol.)]TJ /F1 1 Tf 8.9663 0 0 8.9663 522.3116 94.1102 Tm (350,)Tj -45.2531 -1.2203 TD (32946.)Tj /F2 1 Tf 9.9626 0 0 9.9626 107.6031 737.4045 Tm [(SIMUL)-9.7(TANE)-9(OUS)-339(RECONST)-12.2(RUCTI)-10.1(ON)-333.3(OF)-340.6(MULTI)-9.5(PLE)-335.9(SIGNA)-9.9(LING)-10248(135)]TJ ET endstream endobj 49 0 obj <> endobj 50 0 obj <>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 51 0 obj <>stream /GS1 gs BT /F1 1 Tf 8.9663 0 0 8.9663 74.0976 715.4644 Tm 0 0 0 rg 0 Tc 0 Tw [(Jensen,)-279.1(L.J.,)-274.3(Kuhn,)-276.2(M.,)-271.6(Stark,)-273.7(M.,)-277.9(et)-271(al.)-280.3(2009.)-272.9(STRING)-275(8a)-272.8(global)-279.4(view)-273.4(on)-270.9(proteins)-275.9(and)-279.2(their)-276.2(functional)-273.9(interactions)-280.5(in)]TJ 1.0053 -1.2203 TD [(630)-327.3(organisms.)]TJ /F5 1 Tf 6.5252 0 TD [(Nucleic)-339.1(Acids)-333.8(Res,)]TJ /F1 1 Tf 7.9985 0 TD [(37,)-337.1(D4126.)]TJ -15.5291 -1.2203 TD [(Kaffman,)-389.4(A.,)-381.7(Rank,)-381.2(N.M.,)-384.8(and)-380.3(OShea,)-388.7(E.K.)-381(1998.)-380.3(Phosphorylation)-388.9(regulates)-381.4(association)-389.4(of)-381(the)-384.3(transcription)-381.4(factor)]TJ 1.0053 -1.2203 TD [(Pho4)-331.7(with)-331.9(its)-336.6(import)-333.7(receptor)-335(Pse1/Kap121.)]TJ /F5 1 Tf 18.3301 0 TD [(Genes)-335.7(Dev.)]TJ /F1 1 Tf 5.0267 0 TD [(12,)-337.1(267383.)]TJ -24.3622 -1.2266 TD [(Kaur,)-376(B.,)-376.8(Cork,)-375(S.M.,)-373.8(Sandberg,)-371.8(E.M.,)-375(et)-372.2(al.)-375.1(2009.)-374(Vasculostatin)-376.7(inhibits)-373.8(intracranial)-379.2(glioma)-377.8(growth)-373.7(and)-374(negatively)]TJ 1.0053 -1.2203 TD [(regulates)-337.2(in)-331.8(vivo)-330.9(angiogenesis)-334.3(through)-338.3(a)-330.7(CD36-dependent)-337.5(mechanism.)]TJ /F5 1 Tf 29.2498 0 TD [(Cancer)-336.6(Res.)]TJ /F1 1 Tf 5.3176 0 TD [(69,)-330.7(121220.)]TJ -35.5727 -1.2203 TD [(Kiaris,)-308.4(H.,)-299.5(Schally,)-308.1(A.V.,)-298.9(and)-304.5(Varga,)-302.1(J.L.)-303(2000.)-304.5(Antagonists)-305.6(of)-298.8(growth)-304.2(hormone-releasing)-306.5(hormone)-302.3(inhibit)-303.5(the)-302.2(growth)]TJ 1.0053 -1.2266 TD [(of)-330.4(U-87MG)-335.8(human)-332.3(glioblastoma)-335.9(in)-331.8(nude)-335.6(mice.)]TJ /F5 1 Tf 19.6706 0 TD (Neoplasia)Tj /F1 1 Tf 4.3944 0 TD [(2,)-331.2(24250.)]TJ -25.0703 -1.2203 TD [(Kim,)-372.7(Y.A.,)-368.5(Wuchty,)-368.8(S.,)-364.3(and)-367.7(Przytycka,)-371.4(T.M.)-365.8(2011.)-367.7(Identifying)-368.4(causal)-369.9(genes)-370.3(and)-367.7(dysregulated)-367.3(pathways)-369.9(in)-369.8(complex)]TJ 1.0053 -1.2203 TD (diseases.)Tj /F5 1 Tf 3.8633 0 TD [(PLoS)-331.6(Comput.)-334.5(Biol.)]TJ /F1 1 Tf 8.5043 0 TD [(7,)-337.5(e1001095.)]TJ -13.373 -1.2266 TD [(Lan,)-414.7(A.,)-407(Smoly,)-411.3(I.Y.,)-412(Rapaport,)-407.2(G.,)-413.3(et)-410.1(al.)-413(2011.)-405.6(ResponseNet:)-418.2(revealing)-411.8(signaling)-409.6(and)-411.9(regulatory)-411.5(networks)-408(linking)]TJ 1.0053 -1.2203 TD [(genetic)-334.3(and)-336.1(transcriptomic)-336.3(screening)-333.1(data.)]TJ /F5 1 Tf 17.5903 0 TD [(Nucleic)-332.7(Acids)-333.8(Res)]TJ /F1 1 Tf 7.4105 0 TD [(.)-338(39,)-330.7(W424W429.)]TJ -26.0061 -1.2203 TD [(Li,)-309.3(Y.,)-305.8(Li,)-303(A.,)-305.8(Glas,)-309.1(M.,)-309.5(et)-302.6(al.)-305.6(2011.)-304.5(c-Met)-313.2(signaling)-302.1(induces)-310.1(a)-305.4(reprogramming)-308.2(network)-306.1(and)-304.4(supports)-308.6(the)-308.5(glioblastoma)]TJ 1.0053 -1.2203 TD [(stem-like)-336(phenotype.)]TJ /F5 1 Tf 8.8268 0 TD [(Proc.)-339.5(Natl.)-329.9(Acad.)-338.3(Sci.)-330.4(U.S.A.)]TJ /F1 1 Tf 12.2159 0 TD [(108,)-336.6(99516.)]TJ -22.048 -1.2266 TD [(Ljubic,)-370.7(I.,)-368.4(Weiskircher,)-368.9(R.,)-364.1(Pferschy,)-369.2(U.,)-369.1(et)-365.9(al.)-368.8(2006.)-361.4(An)-369.1(algorithmic)-369.4(framework)-369.2(for)-364.2(the)-371.7(exact)-369.2(solution)-363.4(of)-368.4(the)-365.4(Prize-)]TJ 1.0053 -1.2203 TD [(Collecting)-330.6(Steiner)-339.4(Tree)-334.1(Problem.)]TJ /F5 1 Tf 13.8472 0 TD [(Mathematical)-336.6(Programming)]TJ /F1 1 Tf 11.8428 0 TD [(105,)-336.6(427449.)]TJ -26.6953 -1.2203 TD [(Macaulay,)-272.6(V.M.)-268.1(2004.)-266.5(The)-266.3(IGF)-268.6(receptor)-271.8(as)-261.9(anticancer)-277.1(treatment)-267.7(target.)]TJ /F5 1 Tf 28.9969 0 TD [(Novartis)-266.6(Found)-269.3(Symp.)]TJ /F1 1 Tf 9.2757 0 TD [(262,)-267(23543;)-266.2(discussion)]TJ -37.2672 -1.2266 TD [(2436,)-329.3(2658.)]TJ -1.0053 -1.2203 TD [(Maere,)-447.3(S.,)-440.2(Heymans,)-442.3(K.,)-438.6(and)-443.6(Kuiper,)-436(M.)-445.7(2005.)-437.2(BiNGO:)-443.4(a)-438.2(Cytoscape)-442.7(plugin)-441.4(to)-439.3(assess)-442.9(overrepresentation)-448(of)-437.9(gene)]TJ 1.0053 -1.2203 TD [(ontology)-332.9(categories)-332.8(in)-338.2(biological)-332.2(networks.)]TJ /F5 1 Tf 18.014 0 TD (Bioinformatics)Tj /F1 1 Tf 6.2913 0 TD [(21,)-330.7(34489.)]TJ -25.3106 -1.2266 TD [(Missiuro,)-297.3(P.V.,)-300.5(Liu,)-296.1(K.,)-299.5(Zou,)-292.1(L.)-299.4(et)-296.3(al.)-299.2(2009.)-291.8(Information)-301(ow)-297.6(analysis)-295.9(of)-298.8(interactome)-300.7(networks.)]TJ /F5 1 Tf 39.1072 0 TD [(PLoS)-293.6(Comput)-300(Biol.)]TJ /F1 1 Tf 8.1439 0 TD (5,)Tj -46.2458 -1.2203 TD (e1000350.)Tj -1.0053 -1.2203 TD [(Ourfali,)-328.3(O.,)-331.1(Shlomi,)-326.3(T.,)-327.6(Ideker,)-326.2(T.,)-327.6(et)-321.6(al.)-330.8(2007.)-323.4(SPINE:)-326.4(a)-330.7(framework)-324.9(for)-332.5(signaling-regulatory)-330.1(pathway)-324.9(inference)-330.7(from)]TJ 1.0053 -1.2266 TD [(cause-effect)-337.8(experiments.)]TJ /F5 1 Tf 10.6731 0 TD (Bioinformatics)Tj /F1 1 Tf 6.2913 0 TD [(23,)-330.7(i35966.)]TJ -17.9697 -1.2203 TD [(Shannon,)-411.5(P.,)-408.6(Markiel,)-414(A.,)-407(Ozier,)-407.3(O.,)-413.3(et)-410.1(al.)-406.7(2003.)-412(Cytoscape:)-408.3(a)-412.9(software)-406.7(environment)-412(for)-408.4(integrated)-415.4(models)-406.6(of)-412.6(bio-)]TJ 1.0053 -1.2203 TD [(molecular)-333.2(interaction)-336.7(networks.)]TJ /F5 1 Tf 13.2339 0 TD [(Genome)-337.3(Res.)]TJ /F1 1 Tf 5.6969 0 TD [(13,)-330.7(2498504.)]TJ -19.9361 -1.2203 TD [(Sharan,)-265.3(R.,)-256.7(and)-260.2(Ideker,)-262.9(T.)-261.5(2006.)-260.2(Modeling)-260.2(cellular)-264.6(machinery)-259.6(through)-262.4(biological)-256.3(network)-261.8(comparison.)]TJ /F5 1 Tf 41.4404 0 TD [(Nat.)-263.1(Biotechnol.)]TJ /F1 1 Tf -40.435 -1.2266 TD [(24,)-330.7(42733.)]TJ -1.0053 -1.2203 TD [(Silverstein,)-261.1(R.L.,)-258.9(and)-253.9(Febbraio,)-262(M.)-256(2009.)-253.9(CD36,)-261.9(a)-254.8(scavenger)-262(receptor)-259.2(involved)-259.5(in)-256(immunity,)-258.4(metabolism,)-257.1(angiogenesis,)]TJ 1.0053 -1.2203 TD [(and)-329.7(behavior.)]TJ /F5 1 Tf 5.874 0 TD [(Sci.)-330.4(Signal.)]TJ /F1 1 Tf 4.9572 0 TD [(2,)-331.2(re3.)]TJ -11.8365 -1.2266 TD [(Suthram.,S.,)-340(Beyer,)-341.4(A.,)-337.4(Karp,)-338.1(R.M.,)-335.7(et)-340.6(al.)-337.2(2008.)-336.1(eQED:)-339.2(an)-336.6(efcient)-341.4(method)-342.2(for)-332.5(interpreting)-342.7(eQTL)-338.5(associations)-339.5(using)]TJ 1.0053 -1.2203 TD [(protein)-332.1(networks.)]TJ /F5 1 Tf 7.4231 0 TD [(Mol.)-336.4(Syst.)-331.1(Biol.)]TJ /F1 1 Tf 6.658 0 TD [(4,)-331.2(162.)]TJ -15.0865 -1.2203 TD [(Uhrbom,)-350.9(L.,)-340.3(Hesselager,)-348.8(G.,)-350.1(Nister,)-346.3(M.,)-341.2(et)-346.9(al.)-349.8(1998.)-342.4(Induction)-343.8(of)-349.4(brain)-341.7(tumors)-349.9(in)-344.5(mice)-345.6(using)-344.2(a)-343.4(recombinant)-351.2(platelet-)]TJ 1.0053 -1.2266 TD [(derived)-330.5(growth)-335.8(factor)-333.6(B-chain)-335.2(retrovirus.)]TJ /F5 1 Tf 17.173 0 TD [(Cancer)-336.6(Res)]TJ /F1 1 Tf 5.0583 0 TD [(58,)-337.1(52759.)]TJ -23.2367 -1.2203 TD [(Vanunu,)-353.5(O.,)-356.4(Magger,)-355.9(O.,)-350.1(Ruppin,)-350.2(E.)-356.3(et)-353.2(al.)-349.8(2010.)-355.1(Associating)-352.3(genes)-357.7(and)-348.7(protein)-357.4(complexes)-353(with)-350.8(disease)-358(via)-352.7(network)]TJ 1.0053 -1.2203 TD (propagation.)Tj /F5 1 Tf 5.3745 0 TD [(PLoS)-331.6(Comput.)-334.5(Biol.)]TJ /F1 1 Tf 8.5043 0 TD [(6,)-337.5(e1000641.)]TJ -14.8841 -1.2203 TD [(Yeang,)-337.4(C.H.,)-331.9(Ideker,)-338.8(T.,)-334(and)-336.1(Jaakkola,)-333.9(T.)-331(2004.)-336.1(Physical)-331.2(network)-337.7(models.)]TJ /F5 1 Tf 30.7357 0 TD [(J.)-333.6(Comput.)-334.5(Biol.)]TJ /F1 1 Tf 7.0437 0 TD [(11,)-330.7(24362.)]TJ -37.7794 -1.2266 TD [(Yeger-Lotem,)-419(E.,)-416.1(Riva,)-416.8(L.,)-416.1(Su,)-411.5(L.J.,)-413.4(et)-416.5(al.)-419.4(2009.)-412(Bridging)-416.1(high-throughput)-414.6(genetic)-416.5(and)-418.3(transcriptional)-418.4(data)-411.6(reveals)]TJ 1.0053 -1.2203 TD [(cellular)-334.2(responses)-335.4(to)-331.8(alpha-synuclein)-340.7(toxicity.)]TJ /F5 1 Tf 19.0256 0 TD [(Nat.)-332.7(Genet.)]TJ /F1 1 Tf 5.0077 0 TD [(41,)-337.1(31623.)]TJ -25.0387 -1.2203 TD [(Zarzov,)-317.1(P.,)-313.8(Mazzoni,)-315(C.,)-313.6(and)-317.1(Mann,)-313.9(C.)-317(1996.)-310.8(The)-316.9(SLT2\()-80.6(MPK1\))-318.9(MAP)-310.9(kinase)-316.9(is)-314.1(activated)-320.8(during)-313.5(periods)-310.3(of)-317.8(polarized)]TJ 1.0053 -1.2267 TD [(cell)-333.4(growth)-335.8(in)-331.8(yeast.)]TJ /F5 1 Tf 8.713 0 TD [(Embo.)-332.9(J.)]TJ /F1 1 Tf 3.9518 0 TD [(15,)-330.7(8391.)]TJ -13.6701 -1.2203 TD [(Ziegler,)-274(D.S.,)-275.2(Wright,)-271.8(R.D.,)-275(Kesari)-272.3(S.,)-269.5(et)-271(al.)-273.9(2008.)-272.9(Resistance)-272.8(of)-273.5(human)-275.4(glioblastoma)-272.7(multiforme)-274.8(cells)-270.9(to)-268.6(growth)-272.6(factor)]TJ 1.0053 -1.2203 TD [(inhibitors)-331.1(is)-333(overcome)-338.3(by)-334.1(blockade)-336.2(of)-330.4(inhibitor)-336.8(of)-330.4(apoptosis)-337.2(proteins.)]TJ /F5 1 Tf 28.8072 0 TD [(J.)-333.6(Clin.)-329.9(Invest.)]TJ /F1 1 Tf 6.3166 0 TD [(118,)-336.6(310922.)]TJ 9.9626 0 0 9.9626 391.8046 231.5338 Tm [(Address)-345.5(correspo)-9.1(ndence)-340(to:)]TJ /F5 1 Tf 2.3616 -1.2007 TD [(Prof.)-337.2(Ernest)-341.4(Fraenk)-9.2(el)]TJ -7.9326 -1.195 TD [(77)-337.3(Mass.)-338.6(Avenue)-339.8(Bu)-7(ilding)-337.2(16,)-332(Ro)-7(om)-335.5(241)]TJ 7.3863 -1.2007 TD [(Biologi)-7.7(cal)-336.9(Engine)-8.9(ering)]TJ -6.1116 -1.2007 TD [(Massachus)-9.3(etts)-335.9(Institut)-8.9(e)-332.6(o)0(f)-334.3(T)0(e)-8.2(chnology)]TJ 6.2255 -1.2007 TD [(Cambr)-8(idge)-7.6(,)-330.4(M)0(A)-339.8(02139)]TJ -4.1313 -2.4014 TD (E-mail:)Tj /F1 1 Tf 3.403 0 TD [(fraenkel-a)-12.1(dmin@m)-8.1(it.edu)]TJ /F2 1 Tf -33.0905 59.176 TD [(13)-7.2(6)]TJ 34.5644 0 TD [(TUNCBA)-12.7(G)-334.4(E)0(T)-335.3(AL.)]TJ ET endstream endobj 52 0 obj [/Indexed/DeviceRGB 255 53 0 R] endobj 53 0 obj <>stream 8;X]O>EqN@%''O_@%e@?J;%+8(9e>X=MR6S?i^YgA3=].HDXF.R$lIL@"pJ+EP(%0 b]6ajmNZn*!='OQZeQ^Y*,=]?C.B+\Ulg9dhD*"iC[;*=3`oP1[!S^)?1)IZ4dup` E1r!/,*0[*9.aFIR2&b-C#soRZ7Dl%MLY\.?d>Mn 6%Q2oYfNRF$$+ON<+]RUJmC0InDZ4OTs0S!saG>GGKUlQ*Q?45:CI&4J'_2j$XKrcYp0n+Xl_nU*O( l[$6Nn+Z_Nq0]s7hs]`XX1nZ8&94a\~> endstream endobj 54 0 obj <>stream htWyTS9Em=`Zk"$L$d d02ψmmN};Nl[o/{~>7;-[o_16wVo^zrsΚ֢_5iHu9[EL8)!Qb~kV-u=W?}~n͈/˖ĥeH?!GKb_ݘ䊐'HJMcҢ)IYfm3ľIsbbIq/ύg<ҍoo-I x1^;/soJ ~ӟ>̷fpCB_a6N\rDܙDӑIdxi-X6eF=,:wxAډ^A~.Zm#`x>3afJi͋|ɕ,tyD OA7.yOAC2pEb~;--M,Nob0^!d`ih*"S4vzC3LXDd^Xh7ᡥ n^saӎ-R!&Mu_1bNCJ1,*8[":C$ p`0f!zEMjvG{v'k!_AH a&?sގx\`X//[DOv/F\*xv?9]YՌ6o GL Jh ?R;a1ah+1~`BP:&@7!>c|A6)`*/0=+,@~bȌbH滐OO`ml^OZki![ȁV _l6{%(bM#J*IO|-UĆ{Q ƍ)Opa3K~ngA¢u硩 @ퟟ:6DEQh E;SE@:ߜ}g@Lv8/OjaٿpzjMOgrz;|߸D8#nMMg'&J;vbe>Y8ԭEJ]RB\`i#Ykj+@/`FAQJ* ,'EPGbƌx)~ UsҨT{Cyuw͌G$ͥQuI&DB#@|]R[&ƺӥ+%(h=\>HËzlD=8k빺%& _gq±\XSR. lL!GY([A ǩ㌼;a<  6Df`gs6M)U * ?UHΠnv%j+!tp^spb1Ydꨮ;M:[-(Sw&  a$c9E:4w!_f.Q)%Z h夶הiһvcBJaV}<)SiOv\l$cq2U[!+mҏQ\D`5BrdހD\*tE T[Nx7cb46kwJF9ˢ:Q2i&3{o/Ev/jZt$6KhIL}2z4f!huL]"5/BH~k۹ mſm)O7\ :w"ٮx[lI0]gO q&fs(CXV|{~e3?C6#g q9j{RU8LZLJŵLeJJg%og]NK'pxBx+/i:9)~k׶p[PRv6'.evAkqTzkQQ |U綅ɜ\}p v^kqY}[z-B6OuZWaԊ;t*tctU:3'銳G_L*0~ZiyNGE*SYal(o&9K`V%=uG4 t΋ $pTpFWp E"omfb%,hX٥g&}*dG է iޣއ%h]Y$pز6[]wEoD~HdTPh4I΃v" z~I6hTuI>,T&2NN.9if)Wpr0GwK^!pTrs(udՆ7мLU9Dbj .+T$ZXe_i)-dz"CWe ZjLBb5ƎsR z'sO,y–3s`Š2!]؉Gx]77MvDi#;%$Yk蠁qjKY7c.A]6AcTzAF7ij׆.>5g,mxU'C HÔa 3檛.TNlqdF)m:Q(i=VKXeI@^O}qTXh>r^UQjzļ.vv%8t~2g43h4: DdO񴙶#_w"2B*ΧT%ቩQ:]q$;tmQwp]馕_ c59Rn߿FOzڈG vv/^Rd&7\NF^Æ e4ꆯ P45Ǵi:~vE!ɴxSR|Hʝ~OGF]&d:Ek뱆nj9HYiT8hR g 4c1 ZDxT"Uuvlb4CEԇ4"9obUV1w?w@o]hIH/ZDDBVdu_ w^Z+rULb^DĄF'S!w0czO>&O֣=o*ZVӗx\Ue!aU`lz5FQJ' q:dA71gzs> `uTMVr"kfOs`G7BYr\Lu.&qf36C!>u${e$Qd^]a^D`G|Nl^ k5˿~zߡs428Z8FEG<7͆n*MP60yE ]#B;zԏc9T"<.;UJTL'`'o)Y1JsƒnʰҊB2 *x/|D4ae22w$? y)̃ Qu8CܹkFQCJqx `_ ڔʬ5(<vt 'S[F>q$-4uG2c3FRsff2UQV,I*g֢Q., U̎WYͶ!Yupc>G¯nc=cZYh;S*MI<\KCA{5.4 |DMbJ(ڹzvʴݼGaH+woя[zFUTUM!EX!!;tLN'hȐ7_Z@`QS%:Fp׵KHo(ٲ:c dUAQsa./DqdVt8>TdeiT.ύU'r9 m*U0G.VŐ#*ʟ^VP*a'p|4H]W(:k{^@9>-(% 9[[TD> endobj 56 0 obj <> endobj 57 0 obj <>stream hT=o w~ǫ:q]pU5!!DWu=k]%q4 &蜷qy3i :2%jߍ %8E70P ,v^_tx-m]x8m0j#Hn_#̷d{DuQD0+ۍǍDf\rrV$bYݼcZw/Ɲ:rȯbu endstream endobj 58 0 obj <> endobj 59 0 obj <> endobj 60 0 obj <>stream hbd`ab`ddsqvL) 0q6q57+iW <HI1c;# 0 +##tw|}-dܵk Wff.\,Ţ'-r3•L>7\AM]WTUr*Mk=YDzZ u볷-> endobj 62 0 obj <> endobj 63 0 obj <> endobj 64 0 obj <>stream hbd`ab`ddsqvL) {XH x 8R'QJC7n?{ߍ}Пl|?(",ߏEDhe{/XZ4mE }/xCw ;P|Æ J>S۔׭XƱf[7Ȧ/_U)9=nq\3d-^״m{D endstream endobj 65 0 obj <> endobj 66 0 obj <>stream hT=o w~ō:bIUCۨN8;H53 JՁ=FWW|yY;öd0F:?KqɴU'qAɇ ]Ú2Lz73o_%bd, B,t1Jԝf;(k@f; um& bsa ~j endstream endobj 67 0 obj <> endobj 68 0 obj <> endobj 69 0 obj <> endobj 70 0 obj <> endobj 71 0 obj <> endobj 72 0 obj <>stream NDLFIK+AdvPSMP10 qj AdvPSMP10CKY}ߵ}Ebo=g{}`hkVX/Y+3migEv]yhD].n=K:Ufypo]]l1i8zYFֆsIG[xwcpzpnzz~9T~ymcgcccff]\7|bLxzqbs&TW#_Yx|aFb0iqOff`_Qpi}Ϧ뒎_7uNMWVmJ6:(αFi0gfTa endstream endobj 73 0 obj <> endobj 74 0 obj <>stream 8;Z\6d1X>>#ikr7OPea&[9(ahW?Q4Co&-Y,`$BlU*-`0r^isNUefZV($Y9Z<7_/$i J%Y)`)o2A8Ck\gKQ1U//0/$#jB?P_\@s9sK'(%`&YmrpE.SJ=_l<:&YaU"4WGL<:O ;&Tp^W6QrUicg;]8r3(qgUsblW3O-m7hn@se/.fYmbg98i.'69-JV"@NUaD'k,-VM SdXIU7C4P_g(ql@8tt3/j0^#Oajp9?:!LBf0B8 d(l9df_[_O3\SH=0>".@;B,792=#c"^.6%^-qdOiS:.YIhFrqJiB-B22!T?la+Ej] $@Nh.+t^c]-,\a]TE%BnW5JT6A?POKIjM0Y$l~> endstream endobj 75 0 obj <>stream 8;Z]!;%CMe#Xj%>$[SBBCKq$R&N9.c`@T8Ha*mA[V4Ok@6." d2'd*E5_rMIYsF:WR)gVX^1Q%k8j5#,m?@c$rC\jH;ZS>/sR[0HdYc=#'O!hKXm*K W"SDE\)])-2j]he`M1B[2,]jOUQu1*e/pbTN\\P#&\Gh#f+O)X+57N*HikX4,B3]d LFsR]I=I,(*%!5M`1ATe?C< endstream endobj 76 0 obj <>stream 8;Z]"=Ur=l$q,OD$i2odg*@;h2_YF[k+cZjG;@LSJKc/K8cW6I]eqR-^HeQgMXnW1 3H)V9@fboS[43CCXN;jjZA3-9AR4\2Q55Fh6R\Wo>BtLoIb3b:prpsjDS3n^(*;B;$-!;Co.0^Y;!<]U'=hj1X3cD\iR[NtgS)l*,J*n3dejmB#Ig.4>%pOAZhNI6&HQnkOkK6#Kh S-u:e8mu_mh;ILq6(\/X,Y/H,~> endstream endobj 77 0 obj <>stream 8;Z\60p][!'_E#;H\?M*Z3OekZ'WNDXR,<)MGn>h2HK^YZ\!`R,^_cf#VRk&Sr3>. _p!W8J/t,s_230R\n9;$%OK\NR['X&+^A >p1+`Y!CF:*k)LRH*OfL*pD%=YU=hQe#UZ)`aLg4a7l0d`1(IOaZPlaCPRnJR9-,: 2C;jP\-%L!/]O&TU"*AURE"1a(.%'YOHH6mW[OV&.VB@pib3G]pnDRGjf^IC8]!]f q4#;No_(7b3"7Ao)hF0+l=nmdr;(s$@D0:m0G4TA'a NN/EMn,W7KL6K"6XA$%Z(!J0$juo_tF9pkg;dsK5ea8@1G/^t+pj'=";F7--C0bYI 7Fbn^5Oa/\Ml%m-l2X46-@*p2Td71/?R0td@;BhYb\"nU%/:nE%B8:A~> endstream endobj 78 0 obj <>stream 8;Z]!5n:jV#XlB+"hi2g1r`Ju#)b`qS41mp3mOM&>3j^GWKa,*D*"*+?3O4IDL!nP PaX*/,8Q3Wd!Okc*6Z4'NbO0(cI54rX6Jo;*rMV&0*Lm8c#YRJ\X%p]:fgAns3Wi# ,jn$.bM-f]kb"m15K#Y5Z?B7(LjjBKc+e3P?'))HrR"t4& g;qGB;M*dhL~> endstream endobj 79 0 obj <>stream 8;Z]";&4j.#XmGI#2)b$-L)^%W-+QTU1l4jbt%ElF1S%>Xl>aSEJKc\VuanW=TS$/ %Ju.gb)QL4^<>j%fDTU&eG\[^b1BUB"k*#RpNPc?(8.Mrc5MmjE3LQ\n\!^D.!_il\E4K/>^Ihf:.$( 1Q'\Of&PuIAAG+dkg9EZ'Kb?6Q_ure[4C.Wkj#U@&cMg,q?,YFGhuRUJFV,lF^bcW 1FLAk5Eej#8IGS'-&-5Xj9Wb4^RTEW!)Sbnr;~> endstream endobj 80 0 obj <>stream 8;Z\74aPj:%+Sdt.>RFk[?p(\l7TH1hOqPIm"J]GA?(unPI!Y`K^2V8"$mQafYhM# p%/&s=Vf-"#7q"]J1Ic&BWbTYL-O*D^3mWq]#!72Zi002Fm`>8XjYHk_puYMl5sNS Tac&3>_DjfdkjPoSgu-=BP*V@PdsDrV=[;%CM`@^0PZp!c]62JSXR/W%[4G=H?2K F?u36QFOK#FHShkn`c^%S/!FU]cZTM7U`3,Go[4TG"tEVdoGV;T\IO+0(]9AU8['< i3"9/5`V$`QWG>%9Z3JN9i]I>2Vg;_--[Ir^Il#@Aj(aNQIX/l VS(*57Lj'hX*ECs. UQc8d@"/N+oIi.;KGJG&\;f80T>EU!FU:TFVB26WANokrKAbS9qUoO*"$^%DN(UCE6m^V^HD'($h#8O!q(' ;g`l3BV[5LAoi';b3&/b3+]YGEB2&m\DQ7@J[LKG=(dFeQ>6U]7GO*S;1i'oIN?=C StgAbZlGLU3W%1DRBp>5!Y$'na:kACfFl?>@>;o+KTmMlTt]cZCrl[X3AUmBoE *We#nA0GEB:0:/rFdUe`2U](g.[&&1r"Pdo7sKI][C@>f?$uU! >Z0*@\c, endstream endobj 81 0 obj <>stream 8;Z\79,<.&%.sN8b]W3WM^g';8H]1^ChtCk1AS^ajMg/`QoH]5HgV5""^>"&nn@<. 6.kF;XtbHqCf>%YpC=%I?A2XYm52AB92*p!kE=i(r#JaHXB3q^lhgK$P bAm4#)PiU>G7oJ0=ZY#]heu0Ll6>^mWu'As&>Pa4CKch6#t%16i?EY9r?js%U\/V\ j"L`VRp@'-2Me0cmu#8\l\Iocee&?"*XX+JbT:5LU[s9IX-_IRHgAmAk8i[1\*Tqg E=,.OpO*mBYojn8=_bq$+lbG'icnnYkSV,/ir4Q~> endstream endobj 82 0 obj <>stream 8;Z\699t2Q&9KdrER*TijCP$s*+Kbk$d;o;3Wg^V6s>0:@5:lX1!g\9h5q45074Ik U50(TfMg0=-rR8idfBd0;O8>dM8aTXreND6>WkQUMInoej'2J9\O[q!cXS@)\@?S# bqWRc8)u0teu%(t=5G!Y%09@)-E^:((i+s'=,lBt;?kO+VAd%k0G$95&;g endstream endobj 83 0 obj <>stream 8;Z]">nVc4%"u=o"`p6Ke5h5Kfh<#la*jqI\Ek"]59c0f:'Xbqkk<<%\1V40RI\&^ (^48'j%;#JJbgd+N-1m1f=d?)N+_ghfTn7T9)&/s7\dLOf@KtY0K8V9>UII,iT`>Q VMQ%6c*`SZO_`<;Ze:K2C`hX/n_B(CRYtIqM@enJXjQ/ho\'sUqW`^3Er?#6'9\WF =o]lc7J:Rq_V"U`cA,FR86r_fb,G@#%bVh4n9hDT@@7PS+,gGJ6KR1=EX8)8lbojY &ZN3mN&mAmbOfE(=UCkrXMHW[O\6PO!g&\I5s4m%X?;1"Gs8!!I]pQr:r_^'p5p9r RnW&DK&ZKE7>u3k,)o:92[,.KLkJj9>tAUUoI*hF!<=%"GeX~> endstream endobj 84 0 obj <>stream 8;Z]"N=LR`%"rp+([UH==[K"6T.A?IN(]Hso-h J]YtI!m3e3ZddS<\"@:qV"i,&38VhBPF@QkLdV%I3>".gc0.hk/k0<1:>b1f@PT%, I&Ug1HNeG.H$*5CQB9JHd\*mf31A[iq]Nc1\YNru$sq7>_X,O+9iX0I^<_pC:Hr>O MBZa-Ttifd)>&?V*7qIp/\$`[)JDl8nN'u[+1st5A(1R+]eYGUPDs'gXCgkMNp!Fk /!a&cXMJdrHK3,q&@p&!pY>XNin=<:lV4m6UM-b73FU&XZm3]'Q=3aEC%Y7gRRu3f E\lQTNjcCYe7Sao%-`6~> endstream endobj 85 0 obj <>stream 8;Z\7>7SOn%.!jFR-RH#?mXl"&lP*s>5bBX0Xc8'!"Wt&6NmChla'6%&u`q.MWQ). jBW`X^oc$O9,s1bFiq2V3&u*[+sk d/08DbIc,<;k67gS0hKFG]#5mVHo]/^6;E0NXPdo-:h=!EM7KQ; L!bppTI;#)E*Z$CthW5C]M)nKc[?d`t$_Skj5i-:Dc!g.hf"p3@7i( 2I1]TE1grS!?r"bB`i]\>b>h?BALb1)CMB(/SF6r!RI+?r"[llj8?!P<"JS8SK6:Z bTuELaBX"jTZcV=^D32`d%eD8C7W&J%@HNMDT'U?Z!A0+V%el(qiW8RcN.O7GS"r)Wnkgqqs=3 0Og]N~> endstream endobj 86 0 obj <>stream 8;Z\7>7SP)#ikn#j>rL5,p8P_i_%U kO*>S/+k&trN72N&qndlW0eZQJ#1gemOJ!/]-P.1M=!T(,/6>tTX:RQk0Vu-\+gf- W$p.ZKb+L&`4FGlH,ppk%>'W2n4_h9,t?:>d1)":0]@cH\LQ:>$N\I%&qcF''rQ_: *^P&o?&Ls(+a'hH()NjMFuOFZa4iU$ZDk:1&etds':E^QL^ioYVF>.-COcS_''?6* =2<3F;-?eo8^_UhR4DUJ9Y:fYgU(LrY1OK%qrXjS;>c!Rr)p8cd:nPp5ipT=piunL `#aU$q?r9I1J"81e(u/d*#q'NY5nV3B*f"~> endstream endobj 87 0 obj <> endobj 88 0 obj <> endobj 89 0 obj <> endobj 90 0 obj <> endobj 91 0 obj <> endobj 92 0 obj <>stream 2013-02-01T17:15:05+05:30 Arbortext Advanced Print Publisher 9.0.114/W 2013-02-01T17:15:05+05:30 Acrobat Distiller 8.1.0 (Windows) application/pdf untitled uuid:14f4a67e-2bfd-44b1-94c7-6b5107bde1fc uuid:a860c62d-d642-48ff-aefa-3b9f5afc1d9a endstream endobj 93 0 obj <> endobj xref 0 94 0000000000 65535 f 0000026224 00000 n 0000026364 00000 n 0000026469 00000 n 0000039065 00000 n 0000039205 00000 n 0000039372 00000 n 0000054329 00000 n 0000054580 00000 n 0000054808 00000 n 0000055209 00000 n 0000055412 00000 n 0000055697 00000 n 0000055750 00000 n 0000056086 00000 n 0000056301 00000 n 0000056586 00000 n 0000056643 00000 n 0000056786 00000 n 0000056964 00000 n 0000067870 00000 n 0000121510 00000 n 0000121925 00000 n 0000122119 00000 n 0000122262 00000 n 0000122378 00000 n 0000134663 00000 n 0000134806 00000 n 0000134932 00000 n 0000150498 00000 n 0000150641 00000 n 0000150767 00000 n 0000151816 00000 n 0000361082 00000 n 0000361225 00000 n 0000361352 00000 n 0000374482 00000 n 0000374625 00000 n 0000374761 00000 n 0000384266 00000 n 0000439742 00000 n 0000439885 00000 n 0000439991 00000 n 0000453429 00000 n 0000453572 00000 n 0000453678 00000 n 0000467018 00000 n 0000467161 00000 n 0000467267 00000 n 0000479314 00000 n 0000479457 00000 n 0000479563 00000 n 0000489364 00000 n 0000489412 00000 n 0000489926 00000 n 0000495227 00000 n 0000495659 00000 n 0000496165 00000 n 0000496486 00000 n 0000496650 00000 n 0000496913 00000 n 0000497328 00000 n 0000497549 00000 n 0000498030 00000 n 0000498289 00000 n 0000498679 00000 n 0000498797 00000 n 0000499089 00000 n 0000499157 00000 n 0000499314 00000 n 0000499479 00000 n 0000499691 00000 n 0000499895 00000 n 0000500432 00000 n 0000500589 00000 n 0000501103 00000 n 0000501564 00000 n 0000502063 00000 n 0000502724 00000 n 0000503213 00000 n 0000503724 00000 n 0000505018 00000 n 0000505557 00000 n 0000506302 00000 n 0000506824 00000 n 0000507317 00000 n 0000507928 00000 n 0000508502 00000 n 0000508538 00000 n 0000508563 00000 n 0000508624 00000 n 0000508753 00000 n 0000508834 00000 n 0000512373 00000 n trailer <> startxref 116 %%EOF