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[(and)-334.1(Kulkar)-9.3(ni)-334.3(et)-336.1(al.)-336.5(\(2010\))-338.6(and)-334.1(to)-334.3(v)-6.5(alidate)-337.7(the)-336.9(mode)-8.4(l)-333.6(proposed)-341.1(in)-334.3(Section)-338(3.)]TJ
/F6 1 Tf
10.959 0 0 10.959 107.6031 682.0156 Tm
[(4.2.)-496.9(Estimation)-330.4(of)-331.2(the)-334.3(DA)]TJ
/F1 1 Tf
9.9626 0 0 9.9626 117.5811 664.1006 Tm
-.0141 Tc
[(Dete)-14.1(r)9.1(m)-1.3(in)-14.1(i)10.1(n)2.2(g)-356.3(t)-.6(h)-14.1(e)-341.8(n)-14.1(u)7.1(mbe)-14.1(r)-343.8(o)-14.1(f)-342(e)-14.1(q)11(u)-14.1(i)10.1(libr)-14.1(i)8.1(um)-359.8(po)-14.1(i)10.1(n)-14.1(t)10.1(s)-351.8(a)-14.1(n)11(d)-356.3(t)-.6(h)-14.1(e)11(ir)-358.3(sta)-14.1(b)11(ility)-356.3(is)-357.5(a)-358.1(f).2(u)-14.1(n)12.8(d)-14.1(a)11(me)-14.1(n)11(t)-.6(a)-14.1(l)-344.5(ste)-14.1(p)-347.5(in)-356.3(the)-358.1(a).4(n)-14.1(a)11(ly)-14.1(s)11.6(i)-.6(s)-357.5(o)-14.1(f)]TJ
-1.0015 -1.2007 TD
0 Tc
[(b)16.3(i)0(o)24.2(c)0(h)25.1(e)14.5(mi)20.6(c)14.5(a)14.5(l)-413.2(r)14.3(e)14.5(ac)23.4(t)13.5(i)13.5(o)0(n)-399.9(m)12.8(o)16.3(d)0(e)25.1(l)13.5(s.)-400.7(H)12.4(o)16.3(w)12.4(e)0(v)25.1(e)0(r)23.2(,)-410.1(a)-412.3(c)14.5(om)23.4(p)16.3(l)13.5(et)22.4(e)-406.6(c)0(h)25.1(a)0(r)23.2(a)14.5(ct)22.4(e)14.5(r)14.3(iz)22.4(a)14.5(t)13.5(i)13.5(o)0(n)-399.9(o)16.3(f)-412.5(t)13.5(he)-396(sy)25.7(st)23(e)14.5(m)12.8()14.3(s)-411.7(be)25.1(ha)25.1(vi)24.2(o)16.3(r)-412.5(r)14.3(e)14.5(qu)21.2(i)13.5(r)14.3(e)14.5(s)-411.7(t)13.5(h)0(e)]TJ
T*
-.0143 Tc
[(co)-14.3(m)9.1(p)-14.3(u)12.6(t)-.8(a)-14.3(t)8.1(ion)-328(o)2(f)-330(t)-.8(he)-329.8(DA)-326.3(o)-14.3(f)-313.7(ea)-14.3(c)9.1(h)-328(as)-14.3(y)11.4(m)-1.5(p)-14.3(t)9.9(oti)-14.3(c)8.1(ally)-328(st)-14.3(a)8.1(b)-14.3(l)9.9(e)-324.1(eq)-14.3(u)6.9(ilibr)-14.3(i)7.9(um)-325.9(p)-14.3(o)6.9(int.)-327.7(The)-329.8(D)-1.9(A)-326.3(o)2(f)-330(a).2(n)-328(a).2(sy)-14.3(m)9.1(p)-14.3(t)9.9(o)2(tic)-14.3(a)9.1(lly)-328(sta)-14.3(b)10.8(l)-14.3(e)]TJ
T*
-.026 Tc
[(e)-11.5(q)-26(ui)-26(l)-4.6(i)-12.5(b)-9.7(r)-11.7(i)-12.5(u)-26(m)-184.7(p)-26(oi)-26(nt)-12.5(,)]TJ
/F6 1 Tf
7.1416 0 TD
0 Tc
(x)Tj
7.4718 0 0 6.641 183.0614 626.5699 Tm
(e)Tj
/F1 1 Tf
9.9626 0 0 9.9626 186.2929 628.214 Tm
[(,)-171.1(i)13.5(s)-167(a)-173.3(s)15.1(u)0(b)21.2(s)15.1(e)14.5(t)-174.2(o)16.3(f)-173.5(t)13.5(h)16.3(e)-173.3(s)15.1(t)13.5(a)0(t)22.4(e)-167.6(sp)25.7(ac)23.4(e,)]TJ
/F14 1 Tf
11.3697 0 TD
(O)Tj
/F1 1 Tf
.7056 0 TD
[(,)-171.1(s)0(u)25.7(c)14.5(h)-171.5(t)13.5(ha)25.1(t)-174.2(e)14.5(ve)25.1(r)14.3(y)-171.5(s)15.1(t)13.5(at)22.4(e)-167.6(t)0(r)22.2(a)14.5(j)13.5(e)0(c)23.4(t)13.5(or)24.9(y)-171.5(s)15.1(t)13.5(a)0(r)23.2(t)13.5(i)13.5(n)16.3(g)-171.5(i)13.5(n)]TJ
/F14 1 Tf
16.2636 0 TD
(O)Tj
/F1 1 Tf
.8877 0 TD
[(co)25.1(nv)26.9(er)23.2(ge)25.1(s)-172.7(t)13.5(o)]TJ
/F6 1 Tf
5.0646 0 TD
(x)Tj
7.4718 0 0 6.641 532.2896 626.5699 Tm
(e)Tj
/F1 1 Tf
9.9626 0 0 9.9626 535.4645 628.214 Tm
(.)Tj
-41.945 -1.2007 TD
[(DAs)-307.2(are)-309.4(of)-305.1(para)-8.6(moun)-6.6(t)-305.1(importanc)-10.1(e)-304.2(i)0(n)-305.9(biolog)-10.1(ical)-308.1(system)-9.3(s;)-307.1(indeed,)-307.2(whe)-8(n)-308.1(a)-304.2(system)-310.9(that)-312(is)-307.1(operating)-313.8(in)-305.9(the)]TJ
-1.0015 -1.2007 TD
[(neighborh)-7.7(ood)-264.1(of)-265.3(an)-265.1(equi)-7.6(librium)-269.5(point)-265.4(leaves)-270(the)-268.6(boundarie)-9.5(s)-263.7(o)0(f)-259.6(its)-265.1(regi)-9.6(on)-263.3(of)-265.3(attraction,)-271.1(it)-263.1(is)-267.3(usually)-269.9(abruptly)]TJ
T*
[(led)-450.7(to)-448.2(a)-452.1(new)-451.9(operating)-456.1(condition)-455.1(\(corres)-10.3(pondin)-7.3(g)-444.6(t)0(o)-448.2(anot)-7.6(her)-449.9(equili)-9(brium)-450.3(point)-453.2(or)-447.4(to)-448.2(osci)-8.8(llations\).)-455.7(This)]TJ
0 -1.195 TD
[(phenomeno)-8.3(n)-387.7(i)0(s)-381.1(a)0(t)-387.3(the)-388.1(basis)-386.3(of)-384.8(many)-389.6(on-off)-386.1(regulatory)-390.6(mec)-9.4(hanism)-8.2(s)-383.2(o)0(f)-384.8(biological)-392.1(functio)-8.9(ns)-384(and)-385.3(periodic)]TJ
0 -1.2007 TD
[(behavior)-8.7(s)-275.1(a)0(t)-279.2(the)-280(molecu)-8.7(lar,)-282.3(cellular)-10.3(,)-273.5(o)0(r)-282.3(population)-285.2(level)-280.4(and)-282.9(is)-278.6(closely)-283.1(interwea)-11.5(ved)-277.2(with)-280(an)-282.2(important)-284.2(iss)-7.4(ue)]TJ
T*
[(in)-374.2(systems)-375.5(biology,)-375.4(nam)-7.6(ely)-371(the)-376.7(relation)-378.4(betwee)-10.9(n)-370.7(cellular)-380.2(decision)-374.9(mak)-7.6(ing)-374.9(and)-374(biological)-380.7(noise.)-374.1(Cellula)-10.5(r)]TJ
T*
[(decisi)-9.2(on)-394.2(making)-399.6(is)-392.4(the)-399.5(process)-400.2(by)-394.2(which)-399.2(cel)-8.6(ls)-392.4(can)-398.5(assume)-401(differ)-9.4(ent)-393.8(and)-396.7(herita)-10(ble)-393.8(fates)-400.3(modify)-7.1(ing)-397.7(their)]TJ
T*
[(genome)-449.8(or)-441.7(the)-439.3(envi)-7.6(ronment)-447.9(in)-442.5(which)-444.8(they)-445.8(reside)-446.6(\(Balazsi)-451.7(et)-438.6(al.,)-445(2011\).)-444.3(Some)-445.8(exam)-10.2(ples)-441.3(of)-441.7(regulat)-10.7(ory)]TJ
T*
[(molecu)-8.7(lar)-299(switch)-307.2(concern)-302.9(virus,)-300.3(bact)-9.4(eria,)-302(yeast,)-301.9(lower)-304.5(metaz)-9.8(oans,)-302.3(and)-300(mammal)-10.1(s.)-298.2(In)-299.4(lambda)-304.7(phage,)-303.7(a)-298.5(gene)]TJ
T*
[(regulatory)-316.6(network)-311.7(controls)-306.8(the)-308.4(lysis/)-9.6(lysogeny)-307.7(deci)-9.4(sion)-302.9(in)-305.9(which)-313.9(two)-304.9(repress)-9.6(ors)-307.1(\(CI)-306.9(and)-305.7(Cro\))-307.6(opera)-9.4(te)-307.7(as)-306.1(a)]TJ
T*
[(mutual)-345.5(toggle)-341.9(switch)-341.4(\(lamb)-8.2(da)-339.1(switch\))-344.1(with)-342.6(bistable)-343.5(dynamic)-9.5(s)-337.7(\(Gardn)-8.6(er)-335.3(et)-341.8(al.,)-336.9(2000)-8.7(\).)-333.2(Anoth)-10.5(er)-335.3(examp)-10.9(le)-336.1(is)]TJ
0 -1.195 TD
[(represe)-10.1(nted)-366.1(by)-365.7(the)-371(Nanog-O)-11.3(ct4)-365.3(gene)-370.8(regulat)-10.7(ory)-362.8(networ)-9.3(k,)-365.3(which)-370.8(cont)-7.6(rols)-367.5(embryoni)-10.5(c)-366.8(stem)-365.1(cel)-8.6(l)-362(dif)-7(ferenti-)]TJ
0 -1.2007 TD
[(ation.)-461.1(In)-458.8(the)-462.1(latter)-462.3(system)-9.3(,)-455.6(regulat)-10.7(ory)-459.5(interactions)-11.6(,)-455.6(involvi)-7.9(ng)-456.8(posi)-7(tive)-459.9(and)-459.3(negativ)-8.7(e)-457.8(feed)-8.6(back,)-462.2(generat)-9.7(e)]TJ
T*
[(bistabil)-8.7(ity)-332.2(from)-340.6(noise-induc)-9.3(ed)-339.1(transitions)-344.2(\(Chickar)-9.7(mane)-340.2(et)-336.1(al.,)-331.2(2)-6.5(006\).)]TJ
1.0015 -1.2007 TD
[(Typical)-281.7(informat)-9.5(ion)-278.2(that)-277.8(one)-277.2(can)-279(derive)-280.3(from)-283.7(the)-274.3(know)-7(ledge)-283.3(of)-276.6(the)-274.3(DA)-282.5(is)-272.9(the)-280(extent)-281.1(of)-276.7(the)-280(perturb)-8.1(ations)]TJ
-1.0015 -1.2007 TD
[(that)-255.1(the)-251.5(system)-254(can)-256.2(tolerate)-255(witho)-7.6(ut)-249(changing)-257.1(its)]TJ
/F6 1 Tf
19.6495 0 TD
[(operati)-8.1(ve)-249.8(condi)-8.4(tion)]TJ
/F1 1 Tf
7.8473 0 TD
[(.)-245.1(I)0(n)-253.9(other)-255(words,)-256(the)-251.5(DA)-254.1(is)-250.2(an)-248(indicat)-11.5(or)]TJ
-27.4967 -1.2007 TD
[(of)-418.9(the)-427.9(capabilit)-11.9(y)-416.2(o)0(f)-424.6(the)-422.2(syst)-8.2(em)-422.3(to)-419.7(adapt)-425.6(to)-425.4(changing)-427.8(envi)-7.6(ronmental)-431.2(conditions,)-429(which)-427.7(is)-420.9(reco)-8.6(gnized)-426.3(in)]TJ
T*
[(biology)-340.9(as)-334.6(an)-333.4(esse)-9(ntial)-338.2(feature)-341.8(for)-336.3(every)-339.4(living)-337.2(organ)-7.6(ism.)]TJ
1.0015 -1.2007 TD
[(Unfortunat)-11.4(ely,)-240.5(the)-240.1(exact)-245.2(com)-7.6(putation)-243.8(of)-242.5(the)-240.2(DA)-242.7(for)-239.6(a)-241.6(gener)-9.4(ic)-239.4(nonlinea)-9.5(r)-236.1(syst)-8.2(em)-240.2(is)-238.8(a)-241.6(very)-240.1(dif)-7( cult)-243.6(problem)]TJ
-1.0015 -1.195 TD
[(to)-288.8(solv)-7(e,)-293.1(especially)-297.4(for)-296.5(systems)-295.8(of)-293.7(nontriv)-7.1(ial)-288.4(dim)-8.6(ension.)-295.2(A)-289.2(mor)-7.8(e)-287.1(aff)-8(ordable)-292.5(probl)-8.6(em)-291.4(is)-290(that)-294.9(of)-293.7(determin)-9.3(ing)]TJ
0 -1.2007 TD
[(an)-498.4(estim)-10.2(ate)-498(of)-498.6(\(and)-501.9(possi)-9(bly)-500.1(close)-500.7(to\))-502.1(the)-501.9(actual)-504.8(DA.)-499.2(Sim)-7.8(ilarly)-500.3(to)-499.4(wha)-8(t)-492.9(has)-506(been)-501.7(discusse)-10.3(d)-495.8(for)-501.3(the)]TJ
T*
[(multistabi)-10.9(lity)-324.3(anal)-9.4(ysis,)-327.2(the)-325.5(probl)-8.6(em)-325.5(of)-327.9(DA)-328.1(estimat)-10.5(ion)-323.7(is)-329.8(greatly)-329.4(simpl)-8.4(i ed)-325.5(whe)-8(n)-325.1(dealing)-333.1(with)-325.5(the)-331.2(class)-331.2(of)]TJ
T*
[(nonlinea)-9.5(r)-332.8(quadratic)-338.4(system)-9.3(s.)-332.4(In)-327.9(partic)-10(ular,)-334.3(below)-336.7(we)-331.6(reca)-10.4(ll)-331.4(the)-331.2(main)-335.5(resu)-8(lt)-331.4(of)-327.9(Am)-9(ato)-331.2(et)-330.4(al.)-336.5(\(2007\),)-333.3(whi)-9(ch)]TJ
T*
[(allows)-443.8(to)-442.5(easily)-447.3(and)-442.2(ef cientl)-10.3(y)-438.9(solve)-442(the)-445(aforement)-11.1(ioned)-440.8(probl)-8.6(em.)-439.7(Since)-447.5(the)-439.3(adopt)-8.4(ed)-441.5(method)-445.1(yields)-439.9(a)]TJ
T*
[(polytopi)-8.7(c)-332.6(estimat)-10.5(e)-332.6(o)0(f)-333.6(the)-336.9(DA,)-339.8(let)-334(us)-338.5( rst)-338.2(recall)-336.1(the)-336.9(fol)-7(lowing)-338.4(de nition)-10.5(:)]TJ
/F2 1 Tf
1.0015 -2.4014 TD
[(Denition)-342.1(1.)]TJ
/F1 1 Tf
6.3108 0 TD
[(A)-334.8(polytope)-343.5(\(or)-336.3(box\))]TJ
/F15 1 Tf
8.5757 0 TD
(P)Tj
/F7 1 Tf
1.508 0 TD
()Tj
/F12 1 Tf
1.0471 0 TD
(R)Tj
/F6 1 Tf
6.9738 0 0 6.9738 298.5448 309.4865 Tm
(n)Tj
/F1 1 Tf
9.9626 0 0 9.9626 305.8582 305.4046 Tm
[(can)-335.9(be)-333.4(descr)-10.6(ibed)-337.7(as)-334.6(follows:)]TJ
/F15 1 Tf
-6.1003 -2.0201 TD
(P)Tj
/F7 1 Tf
1.3942 0 TD
()Tj
/F1 1 Tf
.9389 0 TD
(conv)Tj
/F7 1 Tf
1.9519 0 TD
(f)Tj
/F6 1 Tf
.5008 0 TD
(x)Tj
/F8 1 Tf
6.9738 0 0 6.9738 297.2408 283.748 Tm
(\()Tj
/F6 1 Tf
.3252 0 TD
(i)Tj
/F8 1 Tf
.2764 0 TD
(\))Tj
/F1 1 Tf
9.9626 0 0 9.9626 304.2141 285.2787 Tm
()Tj
/F6 1 Tf
.5008 0 TD
(x)Tj
/F8 1 Tf
6.9738 0 0 6.9738 313.6818 283.748 Tm
(\()Tj
/F1 1 Tf
.3252 0 TD
(2)Tj
/F8 1 Tf
.4959 0 TD
(\))Tj
/F1 1 Tf
9.9626 0 0 9.9626 322.1857 285.2787 Tm
()Tj
/F9 1 Tf
.6658 0 TD
.1682 Tc
(...)Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F6 1 Tf
.5008 0 TD
(x)Tj
/F8 1 Tf
6.9738 0 0 6.9738 351.3826 283.748 Tm
(\()Tj
/F6 1 Tf
.3252 0 TD
(p)Tj
/F8 1 Tf
.4959 0 TD
(\))Tj
/F7 1 Tf
9.9626 0 0 9.9626 359.8865 285.2787 Tm
(g)Tj
/F8 1 Tf
16.2807 0 TD
(\()Tj
/F1 1 Tf
.3244 0 TD
(8a)Tj
/F8 1 Tf
.9503 0 TD
(\))Tj
/F7 1 Tf
-28.9137 -1.6104 TD
.1689 Tc
(f)Tj
/F6 1 Tf
1.4397 0 TD
0 Tc
(x)Tj
/F7 1 Tf
.7284 0 TD
(2)Tj
/F12 1 Tf
.9333 0 TD
(R)Tj
/F6 1 Tf
6.9738 0 0 6.9738 284.8251 273.3165 Tm
(n)Tj
/F9 1 Tf
9.9626 0 0 9.9626 291.5716 269.2346 Tm
(:)Tj
/F6 1 Tf
.5463 0 TD
(a)Tj
6.9738 0 0 6.9738 302.0031 267.7039 Tm
(k)Tj
.5447 .8048 TD
(T)Tj
9.9626 0 0 9.9626 310.7338 269.2346 Tm
(x)Tj
/F16 1 Tf
.4496 0 TD
(p)Tj
/F1 1 Tf
1.0015 0 TD
(1)Tj
/F6 1 Tf
1.0015 0 TD
(k)Tj
/F7 1 Tf
.6316 0 TD
()Tj
/F1 1 Tf
.9389 0 TD
[(1)-168.5(2)]TJ
/F9 1 Tf
2.1738 0 TD
.1682 Tc
(...)Tj
/F1 1 Tf
1.3145 0 TD
0 Tc
()Tj
/F6 1 Tf
.5008 0 TD
(q)Tj
/F7 1 Tf
.5008 0 TD
(g)Tj
/F8 1 Tf
12.6501 0 TD
(\()Tj
/F1 1 Tf
.3187 0 TD
.0065 Tc
(8b)Tj
/F8 1 Tf
1.0072 0 TD
0 Tc
(\))Tj
/F1 1 Tf
-42.8783 -2.0031 TD
(where)Tj
/F6 1 Tf
2.8054 0 TD
(p)Tj
/F1 1 Tf
.8536 0 TD
(and)Tj
/F6 1 Tf
1.8039 0 TD
(q)Tj
/F1 1 Tf
.8536 0 TD
[(are)-360.7(suitable)-360.6(integer)-10.7(s)-349.1(n)0(u)-7.2(mbers,)]TJ
/F6 1 Tf
12.6672 0 TD
(x)Tj
7.4718 0 0 6.641 301.1526 247.6346 Tm
[(\(i)-8.2(\))]TJ
/F1 1 Tf
9.9626 0 0 9.9626 311.8109 249.2787 Tm
[(denotes)-360(the)]TJ
/F6 1 Tf
5.002 0 TD
(i)Tj
/F1 1 Tf
.2845 0 TD
[(th)-357.1(vertex)-360(of)]TJ
/F15 1 Tf
5.1898 0 TD
(P)Tj
/F1 1 Tf
1.2292 0 TD
[(,)-353.2(and)-356.9(conv[)]TJ
/F17 1 Tf
4.6947 0 TD
($)Tj
/F1 1 Tf
.4496 0 TD
[(])-355.6(indicates)-363.1(the)]TJ
-37.3471 -1.2007 TD
[(operation)-342.3(of)-333.6(taking)-341.9(the)-336.9(convex)-338.2(hull)-338.6(of)-333.6(the)-336.9(argumen)-8.7(t.)]TJ
1.0015 -1.2007 TD
[(Next,)-302.1(we)-308.8(state)-304.3(the)-302.7(probl)-8.5(em)-302.8(that)-306.3(is)-301.4(solved)-306.2(by)-303.1(the)-302.7(propos)-7.7(ed)-304.9(method.)-303.2(Not)-9(e)-298.5(that,)-306.7(for)-302.2(the)-308.4(sake)-303.7(of)-299.4(simpl)-8.4(icity,)]TJ
-1.0015 -1.195 TD
[(the)-285.7(statemen)-10.3(t)-282.4(o)0(f)-288(the)-285.7(problem)-294.2(refers)-288.4(to)-283.1(the)-285.7(equi)-7.6(librium)-286.6(po)-7.2(int)-281(in)-288.8(the)-285.7(origin.)-285.6(How)-10.2(ever,)-287.8(it)-285.9(is)-284.3(easy)-286.7(to)-283.1(gener)-9.4(alize)]TJ
0 -1.2007 TD
[(the)-262.9(de nition)-266.5(and)-260.2(the)-257.2(proce)-9.4(dure)-262.9(to)-254.7(equi)-7.6(librium)-263.8(points)-261.7(differ)-9.4(ent)-257.2(than)-263.7(zero)-8.6(,)-256.5(via)-257.2(a)-258.6(change)-266(of)-259.6(sta)-8(te)-256.5(variabl)-10.7(es,)-261(as)]TJ
T*
[(shown)-339(in)-334.3(Amato)-340.2(et)-336.1(al.)-336.5(\(2007\).)]TJ
/F2 1 Tf
1.0015 -2.9989 TD
[(Problem)-411.8(2.)]TJ
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T*
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T*
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T*
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T*
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T*
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T*
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[(less)-436.8(of)-437.9(the)-434.9(initial)-442.7(concentration)-441.6(of)]TJ
T*
[(Gal80p,)-705.3(whereas)-706.5(different)-705.5(initial)]TJ
T*
[(concentrations)-562.5(of)-564.4(internalized)-566.3(ga-)]TJ
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[(lactose)-335.5(lead)-342(the)-340.1(system)-338.2(to)-338.2(different)]TJ
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[(equilibrium)-335.4(conditions.)]TJ
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9.9626 0 0 9.9626 107.6031 737.4045 Tm
[(BISTAB)-11.7(ILITY)-338.2(ANA)-8.4(LYSIS)-342.1(IN)-336.7(THE)-339.6(GAL)-338.8(NETWO)-10.1(RK)-17757.8(157)]TJ
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[(far)-405.8(a)4.2(re)-399.9(not)-400.8(a)4.2(ble)-405.6(t)3.2(o)-403.8(r)4(ep)5.9(rod)5.9(u).2(ce)-399.9(persistent)-400.8(memo)5.9(ry)]TJ
20.9355 0 TD
.0113 Tc
[(of)-401.2(th)4.8(e)-406.7(p)-.8(ast)-401.9(e)3.1(xposure)-401(t)2.1(o)-404.9(g)-.8(alactose,)-404.5(a)-401(k)-.8(ey)-404.9(property)-404.9(o)4.8(f)]TJ
-20.9355 -1.2007 TD
.0115 Tc
[(th)5(e)-508.9(G)-4.6(AL)-506.9(regulatory)-507.1(n)-.6(etwork)5(,)-506.7(w)-4.6(hich)-512.8(h)5(a)-2.4(s)-508.3(b)-.6(een)-507.1(e)-2.4(x)5(p)-.6(er)]TJ
22.8476 0 TD
[(imentally)-507(e)3.4(videnced)-507(in)-507(Acar)-509(et)-509.8(al.)-506.6(\()3.2(200)5.1(5\).)-506.6(B).4(y)]TJ
-22.8476 -1.2007 TD
.0127 Tc
[(exploitin)6.2(g)-369.3(CRNT)-369.1(t)3.5(o)-363.6(a)-1.2(na)4.5(ly)6.2(ze)-365.4(the)-365.4(m)-3(o)6.2(d).6(els)-364.8(b).6(as)5.1(ed)-363.6(on)-363.6(ma)4.5(ss)5.1(-ac)4.5(t)3.5(io)6.2(n)-369.3(k).5(ine)4.5(t)-2.2(ic)4.5(s,)-363.3(we)-365.4(ha)4.5(ve)-365.4(fo)6.2(und)-363.6(th)6.2(at)-366.4(the)-365.4(m)2.7(ode)4.5(l)]TJ
T*
.0124 Tc
[(can)5.9(not)-497.6(e)-1.5(x)5.9(h).3(ib)5.9(it)-497.6(the)-496.6(p).3(ersistent)-497.6(m)2.4(emory)-494.8(f)4(eature)-502.3(b)5.9(eca)]TJ
21.9826 0 TD
.0116 Tc
[(use)-497.4(t)2.4(he)-497.4(structure)-497.4(o)-.5(f)-497.6(t)2.4(he)-497.4(underlying)-495.6(reaction)-501.3(n)5.1(et-)]TJ
-21.9826 -1.2007 TD
.0109 Tc
[(w)-5.2(o)-1.2(rks)-412.2(i)1.7(s)-412.2(s)-2.4(uch)-416.7(t)1.7(hat)-413.7(t)1.7(hey)-411(c)-3(annot)-413.7(admit)-408(m)-4.8(ultiple)-418.4(steady)-411(s)]TJ
23.6499 0 TD
.0112 Tc
[(tates,)-410.3(regardless)-417.5(of)-412.6(the)-418.1(v)4.7(alues)-411.9(a)3(ssigned)-410.7(to)-410.7(the)]TJ
-23.6499 -1.2007 TD
.0113 Tc
[(kinetic)-452.2(parameters.)]TJ
ET
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288.933 0 0 254.438 216.057 467.603 cm
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/F2 1 Tf
8.9663 0 0 8.9663 74.0976 652.0817 Tm
0 Tc
[(FIG.)-764.7(4.)]TJ
/F1 1 Tf
4.5462 0 TD
[(State)-761.4(response)-764.7(of)-766.7(the)]TJ
-4.5462 -1.2266 TD
[(concentrations)-670(of)-665.5(Gal4p)]TJ
/F2 1 Tf
11.1283 0 TD
(\(a\))Tj
/F1 1 Tf
1.8273 0 TD
(and)Tj
-12.9556 -1.2203 TD
(Gal2p)Tj
/F2 1 Tf
3.0982 0 TD
(\(b\))Tj
/F1 1 Tf
1.8653 0 TD
[(from)-651.7(perturbed)-648.3(initial)]TJ
-4.9635 -1.2203 TD
[(conditions)-472.4(belonging)-467.6(to)-470.9(the)-466.5(boxes)]TJ
/F15 1 Tf
0 -1.2266 TD
(P)Tj
/F1 1 Tf
6.2762 0 0 6.2762 85.1527 606.8975 Tm
(1)Tj
8.9663 0 0 8.9663 92.296 608.2014 Tm
(and)Tj
/F15 1 Tf
1.8463 0 TD
(P)Tj
/F1 1 Tf
6.2762 0 0 6.2762 119.8488 606.8975 Tm
(2)Tj
8.9663 0 0 8.9663 123.4771 608.2014 Tm
[(.)-394.9(Solid)-402.5(\(dashed\))-393(lines)]TJ
-5.5073 -1.2203 TD
[(denote)-341(trajectories)-342.4(with)-331.9(initial)-341.6(con-)]TJ
T*
[(dition)-350.6(included)-344.1(in)]TJ
/F15 1 Tf
7.6191 0 TD
(P)Tj
/F1 1 Tf
6.2762 0 0 6.2762 153.411 584.9573 Tm
(1)Tj
8.9663 0 0 8.9663 160.1574 586.318 Tm
(\(resp.)Tj
/F15 1 Tf
2.5924 0 TD
(P)Tj
/F1 1 Tf
6.2762 0 0 6.2762 194.3999 584.9573 Tm
(2)Tj
8.9663 0 0 8.9663 198.0283 586.318 Tm
(\),)Tj
-13.8219 -1.2266 TD
[(converging)-487.1(to)]TJ
/F6 1 Tf
6.2597 0 TD
(x)Tj
6.2762 0 0 6.2762 134.2488 574.0156 Tm
(e)Tj
/F1 1 Tf
4.483 0 0 4.483 137.0834 573.0518 Tm
(1)Tj
8.9663 0 0 8.9663 144.6236 575.3195 Tm
(\(resp.)Tj
/F6 1 Tf
2.7378 0 TD
(x)Tj
6.2762 0 0 6.2762 173.1401 574.0156 Tm
(e)Tj
/F1 1 Tf
4.483 0 0 4.483 175.9747 573.0518 Tm
(2)Tj
8.9663 0 0 8.9663 179.2062 575.3195 Tm
[(\).)-485.6(Star)]TJ
-11.7227 -1.2203 TD
[(\(circle\))-379.6(markers)-378.1(denote)-379(trajectories)]TJ
T*
[(with)-489.9(initial)-487(condition)-490.6(outside)]TJ
/F15 1 Tf
12.7723 0 TD
(P)Tj
/F1 1 Tf
6.2762 0 0 6.2762 199.6157 552.0754 Tm
(1)Tj
8.9663 0 0 8.9663 74.0976 542.4944 Tm
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/F15 1 Tf
2.5102 0 TD
(P)Tj
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6.2762 0 0 6.2762 107.6031 541.1337 Tm
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8.9663 0 0 8.9663 111.2315 542.4944 Tm
[(\),)-251.6(converging)-259.5(to)]TJ
/F6 1 Tf
6.6391 0 TD
(x)Tj
6.2762 0 0 6.2762 174.7275 541.1337 Tm
(e)Tj
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4.483 0 0 4.483 177.5621 540.1699 Tm
(2)Tj
8.9663 0 0 8.9663 183.0614 542.4944 Tm
(\(resp.)Tj
/F6 1 Tf
-12.1526 -1.2267 TD
(x)Tj
6.2762 0 0 6.2762 78.1228 530.192 Tm
(e)Tj
/F1 1 Tf
4.483 0 0 4.483 80.9575 529.2282 Tm
(1)Tj
8.9663 0 0 8.9663 84.1889 531.4959 Tm
(\).)Tj
/F2 1 Tf
9.9626 0 0 9.9626 74.0976 737.4045 Tm
[(15)-7.2(8)]TJ
33.5629 0 TD
[(COSENTI)-9.5(NO)-339(ET)-335.3(AL.)]TJ
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