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[(T)69.1(e)0(c)20.4(h)0(n)15.5(o)0(l)18.9(o)0(g)15.5(i)13.9(es)13.9(,)-438.6(P)11.4(ai)12.8(sl)17.7(ey)83.4(,)-216.6(U)0(K)19.1(\))-218.6(su)20(pp)15.5(le)18.4(me)17.7(nt)13.2(ed)-206.8(w)12.4(i)0(t)16.5(h)-217(10)15.5(%)-213.7(f)0(o)19.6(e)0(t)12.8(a)0(l)]TJ 0 -1.0471 TD [(bo)15.5(vi)18.9(ne)-457.2(se)19.6(ru)19.6(m,)-459.5(10)21.2(0)-467.4(U)]TJ /F9 1 Tf 8.8659 0.1992 TD (.)Tj /F7 1 Tf 0.2731 -0.1992 TD (mL)Tj 7.472 0 0 6.641 162.879 640.063 Tm (-1)Tj 9.963 0 0 9.963 173.537 635.641 Tm [(pe)15.1(ni)18.9(ci)18.5(ll)16.5(in)-453.5(an)15.1(d)-461.7(1)0(0)15.5(0)]TJ /F10 1 Tf 7.9383 0 TD (m)Tj /F7 1 Tf 0.5634 0 TD (g)Tj /F9 1 Tf 0.4951 0.1992 TD (.)Tj /F7 1 Tf 0.2675 -0.1992 TD (mL)Tj 7.472 0 0 6.641 279.383 640.063 Tm (-1)Tj 9.963 0 0 9.963 58.28 625.153 Tm [(st)17.7(re)19.2(pt)13.2(om)18.1(yc)20.8(in)-225.8(su)14.4(lp)18.9(ha)20.8(te)-226.2(in)-225.8(5%)-225.8(ca)14.7(rb)19.6(on)-229.2(di)18.9(ox)21.2(id)13.2(e)-234.5(i)13.9(n)-234.1(a)0(i)12.8(r)-230(at)-226.2(37)]TJ /F8 1 Tf 21.516 0 TD (8)Tj /F7 1 Tf 0.3756 0 TD (C.)Tj -21.8915 -1.0471 TD [(Th)17.1(e)-314.2(c)0(u)20.8(l)0(t)16.5(u)0(r)14(e)-308.5(fl)17.3(as)13.9(ks)-304.3(w)12.4(e)0(r)13.5(e)-314.2(co)20.8(at)18.4(ed)-303.5(wi)14.9(th)-305.5(a)-314.2(s)0(o)20(l)0(u)18.9(t)0(i)16.5(o)0(n)-303.1(c)0(o)15.1(n)0(t)18.9(a)0(i)18.5(n)0(i)18.9(n)0(g)]TJ 0 -1.0527 TD [(0.)15.9(01)-382.8(mg)]TJ /F9 1 Tf 3.3745 0.1992 TD (.)Tj /F7 1 Tf 0.2675 -0.1992 TD (mL)Tj 7.472 0 0 6.641 108.113 608.655 Tm (-1)Tj 9.963 0 0 9.963 118.091 604.233 Tm [(fi)17.3(b-)13.9(ro)19.6(ne)15.1(ct)18.4(in)18.9(,)-398.7(0)0(.)21.6(0)0(2)15.5(9)-393.4(mg)]TJ /F9 1 Tf 9.0594 0.1992 TD (.)Tj /F7 1 Tf 0.2675 -0.1992 TD (mL)Tj 7.472 0 0 6.641 224.561 608.655 Tm (-1)Tj 9.963 0 0 9.963 234.539 604.233 Tm [(co)15.1(ll)16.5(ag)20.8(en)-388.9(an)15.1(d)]TJ -17.6919 -1.0471 TD [(0.)15.9(1)-302.4(m)0(g)]TJ /F9 1 Tf 2.7884 0.1992 TD (.)Tj /F7 1 Tf 0.2731 -0.1992 TD (mL)Tj 7.472 0 0 6.641 102.274 598.223 Tm (-1)Tj 9.963 0 0 9.963 111.345 593.801 Tm [(BS)17.3(A)-306.3(f)0(o)19.6(r)]TJ /F11 1 Tf 3.659 0 TD ($)Tj /F7 1 Tf 0.8251 0 TD [(1)-302.4(h)-302.4(b)0(e)15.1(f)0(o)19.6(r)0(e)-293.7(s)0(e)13.9(e)0(d)20.8(i)0(n)18.9(g)-308.1(th)18.9(e)-302.8(c)0(e)14.7(l)13.9(ls)12(.)-302(T)12.2(he)]TJ -9.8105 -1.0527 TD [(me)17.7(di)18.9(um)-317.7(wa)16.9(s)-326.3(c)0(h)20.8(a)0(n)15.1(g)0(e)15.1(d)-319.4(tw)14.9(ic)18.4(e)-325.5(w)0(e)16.9(e)0(k)15.1(l)0(y)81.4(.)]TJ /F4 1 Tf 0 -2.4526 TD [(X-ray)-341.2(micr)28.9(oanaly)-7.4(sis)]TJ /F7 1 Tf 1.0015 -1.747 TD [(Ce)16.1(ll)16.5(s)-286.5(w)0(e)16.9(r)0(e)-282.4(c)0(u)15.1(l)0(t)16.5(u)0(r)19.6(e)0(d)-280.8(t)0(o)-282.7(c)0(o)20.8(n)0(f)13.9(l)13.9(u)0(e)15.1(n)0(c)15.1(e)-285.7(on)-280.4(ti)16.5(ta)18.4(ni)13.2(um)-277.8(gr)13.9(i)13.9(d)0(s)-281.6(c)0(o)15.1(-)]TJ -1.0015 -1.0528 TD [(ve)15.1(re)19.2(d)-336.5(w)0(i)14.9(t)0(h)-334(a)-336.9(ca)14.7(rb)19.6(on)15.5(-c)19.2(oa)15.1(t)13.9(e)0(d)-332(F)0(o)16.3(r)0(m)16.5(v)0(a)15.1(r)-338.1(fi)17.3(lm)-331.4(\(M)17.7(er)13.5(ck)20.8(,)-341.8(D)12.4(ar)13.5(m-)]TJ 0 -1.0471 TD [(st)17.7(ad)15.1(t,)-259.6(Ge)16.9(rm)16.5(an)15.1(y\))-259.2(co)15.1(at)18.5(ed)-263.7(w)12.4(i)0(t)16.5(h)-273.9(t)13.9(h)0(e)-263.7(f)0(i)17.3(b)0(r)13.9(o)0(n)21.2(e)0(c)14.7(t)0(i)16.5(n)0(,)-257.2(c)0(o)15.1(l)0(l)16.5(a)0(g)20.8(e)0(n)15.1(,)-267.8(an)15.1(d)]TJ 0 -1.0528 TD [(BS)17.3(A)-238(s)0(o)14.4(l)0(u)18.9(t)0(i)16.5(o)0(n)-229.2(\()0(s)18.4(e)0(e)]TJ /F4 1 Tf 7.3237 0 TD [(Ce)16.1(ll)-228.2(cu)15.1(lt)16.5(ur)54.2(e)]TJ /F7 1 Tf 4.5638 0 TD [(\).)-230.4(C)11.6(e)0(l)18.4(l)0(s)-232.7(w)0(e)16.9(r)0(e)-231.2(i)0(n)18.9(c)0(u)15.1(b)0(a)20.8(t)0(e)18.4(d)-239.8(wi)14.9(th)]TJ -11.8876 -1.0528 TD [(or)-447(wi)14.9(th)18.8(ou)15.5(t)-458.4(4)0(P)22(B)0(A)-454(i)0(n)-447.8(D)0(u)17.3(l)0(b)18.9(e)0(c)14.7(c)0(o)]TJ /F8 1 Tf 12.5192 0 TD (')Tj /F7 1 Tf 0.2106 0 TD 0.4572 Tc [(sm)457.2(o)475.3(d)457.2(i)470.4(f)457.2(i)474.5(e)457.2(d)11.4(E)457.2(a)473.9(g)457.2(l)476.1(e)]TJ /F8 1 Tf 7.0108 0 TD 0 Tc (')Tj /F7 1 Tf 0.2106 0 TD 0.4572 Tc [(sm)457.2(e)469.2(d)457.2(-)]TJ -19.9511 -1.0471 TD 0 Tc [(iu)18.9(m:)15.7(Ha)16.9(m)]TJ /F8 1 Tf 3.6761 0 TD (')Tj /F7 1 Tf 0.2105 0 TD [(s)-212.5(F)11.4(12)-200.7(me)12(di)18.9(um)-203.8(\(1)19.6(:1)18.9(\))-212.9(w)0(i)14.9(t)0(h)-203.1(g)0(l)18.9(u)0(t)18.9(a)0(m)17.7(a)0(x)-201.1(\()0(5)13.9(2)0(4)-200.7(m)0(g)]TJ /F9 1 Tf 16.8839 0.1992 TD (.)Tj /F7 1 Tf 0.2731 -0.1992 TD (L)Tj 7.472 0 0 6.641 273.883 493.568 Tm -0.0185 Tc (-1)Tj 9.963 0 0 9.963 279.836 489.146 Tm 0 Tc (\),)Tj -22.2387 -1.0527 TD [(2%)-419.3(U)12.4(l)0(t)16.5(r)0(o)13.9(s)0(e)19.6(r)-423.5(G)-425.8(\()0(G)15.7(i)0(b)18.9(c)0(o)15.1(,)-421.5(BR)11.8(L)12.2(/)0(L)14.7(i)0(f)17.3(e)-422.3(T)69.1(e)0(c)20.4(h)0(n)15.5(o)0(l)18.9(o)0(g)15.5(i)0(e)18.4(s)0(\))-414(a)0(n)15.1(d)-421.9(50)]TJ /F10 1 Tf 0 -1.0471 TD (m)Tj /F7 1 Tf 0.5634 0 TD (g)Tj /F9 1 Tf 0.4894 0.1992 TD (.)Tj /F7 1 Tf 0.2731 -0.1992 TD (mL)Tj 7.472 0 0 6.641 85.039 472.649 Tm (-1)Tj 9.963 0 0 9.963 94.394 468.227 Tm [(ge)15.1(nt)18.9(am)17.7(ic)18.4(in)-328.3(fo)19.6(r)-332.4(7)0(2)-325.9(h)0(.)-325.5(T)12.2(he)-326.3(ce)14.7(ll)16.5(s)-332(w)0(e)16.9(r)0(e)-327.9(t)0(h)18.8(e)0(n)-326.3(s)0(t)17.7(i)0(m)15.7(u)0(-)]TJ -3.6249 -1.0527 TD [(la)18.4(te)18.4(d)-205.6(w)12.4(it)16.5(h)-199.9(5)-205.6(mM)-194.4(8-)19.6(br)19.6(om)12.4(o-)19.6(cA)16.9(MP)-190.5(or)-196.6(5)-199.9(m)0(M)-194.4(8)0(-)19.6(b)0(r)13.9(o)0(m)18.1(o)0(-)19.6(c)0(A)16.9(M)0(P)]TJ 0 -1.0471 TD [(an)15.1(d)-256.8(5)0(0)]TJ /F10 1 Tf 2.9249 0 TD (m)Tj /F7 1 Tf 0.5634 0 TD [(M)-258.8(g)0(e)20.8(n)0(i)18.9(s)0(t)12(e)0(i)18.5(n)-256.8(fo)19.6(r)-258.4(3)-256.8(mi)15.7(n)-256.8(o)0(r)-247.8(w)0(i)20.6(t)0(h)-248.6(3)0(0)-251.9(n)0(M)-248.2(C)11.6(PX)-249.4(fo)13.9(r)-252.7(1)0(5)]TJ -3.4883 -1.0528 TD [(mi)15.7(n)-382(i)0(n)-373.8(s)0(t)17.7(a)0(n)15.1(d)0(a)20.8(r)0(d)-378.7(R)11.6(in)18.9(ge)15.1(r)]TJ /F8 1 Tf 9.3666 0 TD (')Tj /F7 1 Tf 0.2105 0 TD [(s)-383.2(s)0(o)20(l)0(u)18.9(t)0(i)16.5(o)0(n)15.5(.)-381.6(Th)17.1(e)-382.4(c)0(e)14.7(l)0(l)16.5(s)-383.2(w)12.4(e)0(r)13.5(e)-382.4(ri)17.3(ns)20(ed)]TJ -9.5772 -1.0471 TD [(wi)14.9(th)-390.9(co)20.8(ld)-396.6(di)18.9(st)17.7(il)16.5(le)18.4(d)-399.1(w)0(a)16.9(t)0(e)18.4(r)-400.7(fo)13.9(r)-400.7(s)0(o)20(m)0(e)-392(s)0(e)13.9(c)0(o)20.8(n)0(d)15.5(s)-400.3(be)20.8(fo)13.9(re)-390.5(be)20.8(in)13.2(g)]TJ 0 -1.0527 TD [(fr)18(oz)15.1(en)-189.7(in)-191.7(li)16.5(qu)15.5(i)13.9(d)-205.6(pr)19.6(op)21.2(an)15.1(e)-200.3(c)0(o)15.1(o)0(l)18.9(e)0(d)-189.7(b)0(y)-189.3(l)0(i)16.5(q)0(u)15.5(i)0(d)-191.7(n)0(i)18.9(t)0(r)17.3(o)0(g)15.5(e)0(n)-189.7(\()0(-)18(1)0(8)15.5(0)]TJ /F8 1 Tf 21.442 0 TD (8)Tj /F7 1 Tf 0.3756 0 TD (C\))Tj -21.8176 -1.0471 TD [(an)15.1(d)-336.5(f)0(r)12.4(e)0(e)20.4(z)0(e)14.7(-)0(d)19.6(r)0(i)17.3(e)0(d)-332(o)0(v)15.5(e)0(r)19.2(n)0(i)18.9(g)0(h)15.5(t)-338.9(un)15.5(de)20.8(r)-343.8(v)0(a)20.8(c)0(u)15.1(u)0(m)-334.7(a)0(t)-328.7(-)0(1)13.9(2)0(0)]TJ /F8 1 Tf 19.6495 0 TD (8)Tj /F7 1 Tf 0.3756 0 TD [(C.)-335.9(T)12.2(h)0(e)]TJ -20.025 -1.0528 TD [(fr)18(ee)14.7(ze)20.4(-d)13.9(ri)17.3(ed)-400.3(ce)20.4(ll)16.5(s)-411.7(w)0(e)16.9(r)0(e)-401.9(c)0(o)20.8(a)0(t)12.8(e)0(d)-400.3(w)12.4(it)16.5(h)-410.5(a)-410.9(co)20.8(nd)15.5(uc)20.8(ti)16.5(ve)-400.3(ca)14.7(rb)19.6(on)]TJ 0 -1.0471 TD [(la)18.4(ye)15.1(r)-383.6(b)0(e)20.8(f)0(o)13.9(r)0(e)-373.4(a)0(n)15.1(a)0(l)18.4(y)0(s)20(i)0(s)17.7(.)-387.3(Ge)16.9(ni)18.9(st)17.7(ei)18.4(n)-387.7(a)0(n)20.8(d)-387.7(C)11.6(P)0(X)-380.3(w)12.4(er)13.5(e)-382.4(p)0(r)19.6(e)0(p)15.1(a)0(r)19.2(e)0(d)]TJ 0 -1.0527 TD [(fr)18(om)-220.9(st)17.7(oc)15.1(k)-228.4(s)0(o)20(l)0(u)13.2(t)13.9(io)13.2(ns)-219(in)-220.2(di)18.9(me)17.7(th)13.2(yl)-220.1(su)20(lp)18.9(ho)15.5(xi)18.9(de)-218.2(\(D)15.7(MS)14.4(O\))15.7(.)-228(T)12.2(he)]TJ 0 -1.0471 TD [(co)15.1(nc)20.8(en)15.1(tr)17.3(at)18.5(io)18.9(n)-330.8(o)0(f)-327.5(D)0(M)15.3(S)11.4(O)-334.7(t)0(o)-322.6(w)0(h)17.3(i)0(c)18.4(h)-336.5(th)18.9(e)-331.2(c)0(e)14.7(l)0(l)16.5(s)-332(w)12.4(e)0(r)13.5(e)-331.2(ex)15.1(po)21.2(se)13.9(d)]TJ 0 -1.0527 TD [(wa)16.9(s)]TJ /F11 1 Tf 1.7527 0 TD (#)Tj /F7 1 Tf 0.8251 0 TD [(1%)13.2(.)-228(N)0(o)-221.7(c)0(h)15.1(a)0(n)20.8(g)0(e)15.1(s)-229.6(in)-220.2(th)13.2(e)-228.8(c)0(o)15.1(n)0(c)20.8(e)0(n)15.1(t)0(r)17.3(a)0(t)18.4(i)0(o)18.9(n)0(s)-224.6(o)0(f)-219.4(t)0(h)18.9(e)-234.5(va)20.8(ri)17.3(ou)15.5(s)]TJ -2.5778 -1.0471 TD [(el)18.4(em)17.7(en)15.1(ts)-244.1(me)17.7(as)19.6(ur)14(ed)-240.9(we)16.9(re)-242.5(se)19.6(en)-240.9(in)-242.9(th)18.9(e)-251.6(c)0(e)14.7(l)13.9(ls)-244.1(af)19.2(te)12.8(r)-247.1(e)0(x)15.1(p)0(o)21.2(s)0(u)14.4(r)0(e)-242.5(t)0(o)]TJ 0 -1.0527 TD [(1%)-197.4(DM)15.3(S)11.4(O)-203.9(fo)13.9(r)-201.5(3)-205.6(an)20.8(d)-205.6(1)0(5)-195(m)0(i)15.7(n)0(.)-194.6(C)11.6(el)12.8(l)13.9(s)-206.8(in)18.9(cu)15.1(ba)20.8(te)18.4(d)-205.6(w)0(i)14.9(t)0(h)-191.7(s)0(t)17.7(a)0(n)15.1(d)0(a)15.1(r)0(d)]TJ 0 -1.0471 TD [(Ri)14.1(ng)21.2(er)]TJ /F8 1 Tf 2.6461 0 TD (')Tj /F7 1 Tf 0.2049 0 TD 0.3156 Tc [(s)-10.7(s)315.6(o)335.6(l)315.6(u)334.4(t)315.6(i)332.1(o)315.6(n\()315.6(3o)315.6(r1)315.6(5m)315.6(i)331.3(n)315.6(\)w)315.6(e)332.5(r)315.6(eu)315.6(s)335.6(e)315.6(da)315.6(sc)315.6(o)330.7(n)315.6(t)334.5(r)315.6(o)329.5(l)329.5(.)]TJ -1.8494 -1.0528 TD 0 Tc [(An)17.3(al)18.4(ys)14.4(is)-221.3(wa)16.9(s)-235.3(p)0(e)20.8(r)0(f)18(o)0(r)13.9(m)0(e)17.7(d)-234.1(us)20(in)18.9(g)-234.1(a)-234.5(H)12.4(i)0(t)16.5(a)0(c)14.7(h)0(i)-220.2(H)0(7)17.3(1)0(0)15.5(0)-234.1(el)18.4(ec)20.4(tr)17.3(on)]TJ -1.0015 -1.0471 TD [(mi)15.7(cr)19.2(os)14.4(co)20.8(pe)-280.8(\(H)15.7(it)16.5(ac)20.4(hi)13.2(,)-284.9(T)69.1(ok)21.2(yo)15.5(,)-284.9(J)0(a)13.9(p)0(a)20.8(n)0(\))-282(i)0(n)-277.1(t)0(h)13.2(e)-285.7(sc)13.9(an)20.8(ni)18.9(ng)-280.4(tr)17.3(an)15.1(s-)]TJ 0 -1.0528 TD [(mi)15.7(ss)18.9(io)18.9(n)-484.5(e)0(l)12.8(e)0(c)20.4(t)0(r)17.3(o)0(n)-479.5(m)0(i)15.7(c)0(r)19.2(o)0(s)20(c)0(o)15.1(p)0(y)-473.8(m)0(o)12.4(d)0(e)-474.3(a)0(t)-476.6(1)0(0)15.5(0)-484.5(kV)-477.8(w)12.4(i)0(t)16.5(h)-484.5(an)]TJ 0 -1.0471 TD [(Ox)17.3(fo)19.6(rd)-447(In)13.9(st)17.7(ru)19.6(me)17.7(nt)18.9(s)-457.2(I)0(S)20.4(I)0(S)-446.2(e)0(n)15.1(e)0(r)24.9(g)0(y)21.2(-)0(d)19.6(i)0(s)17.7(p)0(e)15.1(r)0(s)18.4(i)0(v)18.9(e)-456.4(sp)20(ec)14.7(tr)17.3(om)18.1(et)12.8(er)]TJ 0 -1.0528 TD [(sy)20(st)17.7(em)-460.3(\(O)15.7(xf)19.6(or)19.6(d)-467.4(I)0(n)19.6(s)0(t)17.7(r)0(u)13.9(m)0(e)17.7(n)0(t)18.9(s)0(,)-457.6(O)12.4(xf)14(or)19.6(d,)-456.4(UK)19.1(\).)-458(Qu)17.3(an)20.8(ti)16.5(ta)18.4(ti)16.5(ve)]TJ 0 -1.0471 TD [(an)15.1(al)18.5(ys)20(is)-494.5(w)12.4(a)0(s)-492.5(p)0(e)15.1(r)0(f)18(o)0(r)19.6(m)0(e)17.7(d)-501.5(by)-490.9(co)15.1(m)13.2(p)0(a)15.1(r)0(i)17.3(n)0(g)-490.9(t)0(h)18.9(e)-501.9(ra)19.2(ti)16.5(o)-501.5(o)0(f)-486.8(t)0(h)13.2(e)]TJ 0 -1.0528 TD [(ch)15.1(ar)19.2(ac)20.4(te)12.8(ri)17.3(st)17.7(ic)-470.9(pe)20.8(ak)-468.6(an)15.1(d)-478.8(t)0(h)18.9(e)-479.2(ba)20.8(ck)15.1(gr)19.6(ou)15.5(nd)-468.2(un)21.2(de)15.1(r)-480.4(t)0(h)18.9(e)-479.2(pe)20.8(ak)]TJ 0 -1.0471 TD [(\(P)14.7(:)13.9(B)0(\))-411.9(w)0(i)14.9(t)0(h)-407.9(t)13.9(he)-411.7(P)11.4(:)0(B)-407(o)0(f)-412.8(s)0(t)17.7(a)0(n)20.8(d)0(a)15.1(r)0(d)19.6(s)-417.4(co)20.8(ns)14.4(is)17.7(ti)16.5(ng)-405.6(of)-407.2(a)-416.6(g)0(e)15.1(l)0(a)18.4(t)0(i)16.5(n)0(/)]TJ 0 -1.0527 TD [(gl)18.9(yc)15.1(er)19.2(ol)-220.1(ma)17.7(tr)17.3(ix)-220.2(wi)14.9(th)-220.2(mi)15.7(ne)15.1(ra)19.2(l)-230.8(s)0(a)19.6(l)0(t)16.5(s)-229.6(in)-220.2(kn)21.2(ow)17.3(n)-228.4(c)0(o)15.1(n)0(c)15.1(e)0(n)20.8(t)0(r)17.3(a)0(t)18.4(i)0(o)13.2(n)0(s)]TJ 0 -1.0471 TD [([1)19.6(2].)-333.6(Spectr)-8.6(a)-336.9(were)-345.1(acquir)-9.4(ed)-337.7(for)-341.2(100)-338(s)-343.4(and)-338.4(each)-340(cell)-344.4(was)]TJ 0 -1.0528 TD [(analys)-9(ed)-332(only)-341.2(once.)]TJ /F4 1 Tf 0 -2.4526 TD [(Statist)-10.4(ical)-338.3(analysis)]TJ /F7 1 Tf 1.0015 -1.7527 TD [(On)17.3(e-)13.5(w)12.4(a)0(y)-263.7(a)0(n)15.1(a)0(l)18.4(y)0(s)20(i)0(s)-261.2(o)0(f)-264.9(v)0(a)20.8(r)0(i)17.3(a)0(n)15.1(c)0(e)-264.1(a)0(n)20.8(d)-273.9(N)12.4(e)0(w)11.2(m)13.2(an)15.1(-K)15.7(eu)20.8(ls)-266.9(mu)18.1(l-)]TJ -1.0015 -1.0471 TD [(ti)16.5(pl)18.9(e)-314.2(c)0(o)15.1(m)0(p)18.1(a)0(r)13.5(i)13.9(so)14.4(n)]TJ /F4 1 Tf 6.8856 0 TD [(po)15.5(st)-306.7(ho)21.2(c)]TJ /F7 1 Tf 3.6761 0 TD [(te)12.8(st)-306.7(w)12.4(e)0(r)13.5(e)-314.2(us)20(ed)-309.2(to)-305.5(ev)15.1(al)18.4(ua)20.8(te)-311.6(st)17.7(at)18.4(-)]TJ -10.5617 -1.0528 TD [(is)17.7(ti)16.5(ca)20.4(l)-577.9(s)0(i)17.7(g)0(n)21.2(i)0(f)17.3(i)0(c)18.4(a)0(n)15.1(c)0(e)-565.7(w)12.4(he)15.1(n)-569.8(m)0(o)12.4(r)0(e)-561.2(t)0(h)18.9(a)0(n)-565.3(t)0(w)14.9(o)-569.8(gr)19.6(ou)15.5(ps)-560.4(we)11.2(re)]TJ 0 -1.0471 TD [(co)15.1(mp)18.1(ar)19.2(ed)15.1(.)-273.5(W)0(h)14.4(e)0(n)-263.7(t)0(w)14.9(o)-273.9(gr)19.6(ou)15.5(ps)-264.5(we)16.9(re)-271(co)20.8(mp)12.4(ar)19.2(ed)20.8(,)-279.2(a)0(n)-263.7(u)0(n)15.5(p)0(a)20.8(i)0(r)17.3(e)0(d)]TJ 0 -1.0528 TD [(t-)17.3(te)18.4(st)-255.5(w)12.4(a)0(s)-253.5(u)0(s)14.4(e)0(d)20.8(.)-262.1(S)11.4(i)0(g)18.9(n)0(i)13.2(f)0(i)17.3(c)0(a)20.4(n)0(c)15.1(e)-257.2(wa)16.9(s)-263.7(a)0(t)18.4(t)0(r)17.3(i)0(b)18.9(u)0(t)13.2(e)0(d)-252.3(t)13.9(o)-262.5(a)-262.9(p-)19.6(va)15.1(lu)18.9(e)-262.9(o)0(f)]TJ /F10 1 Tf 0 -1.0471 TD (<)Tj /F7 1 Tf 0.5406 0 TD [(0.)15.9(05)15.5(.)]TJ /F6 1 Tf 34.5189 42.7588 TD [(Res)-7.8(ults)]TJ /F7 1 Tf -8.8602 -2.0998 TD [(In)13.9(cu)20.8(ba)15.1(ti)16.5(on)-473.8(wi)14.9(th)-476.2(4P)16.3(BA)-482.5(or)-475.4(st)17.7(im)15.7(ul)18.9(at)18.5(io)13.2(n)-484.5(w)0(i)14.9(t)0(h)-476.2(8)0(-)19.6(b)0(r)13.9(o)0(m)18.1(o)0(-)]TJ -1.0015 -1.0755 TD [(cA)16.9(MP)-389.7(al)18.5(on)21.2(e)-393.8(d)0(i)18.9(d)-393.4(no)21.2(t)-395.8(a)0(f)30.6(f)0(e)13.5(c)0(t)-379.9(t)0(h)13.2(e)-388.1(ce)14.7(ll)16.5(ul)18.9(ar)-384.8(co)20.8(nt)18.9(en)15.1(t)-390.1(o)0(f)-384.4(p)0(h)15.5(o)0(s)20(-)]TJ 0 -1.0698 TD [(ph)15.5(or)19.6(us)14.4(,)-262.2(c)0(h)15.1(l)0(o)18.8(r)0(i)17.3(n)-268.2(or)-253.5(po)15.5(ta)18.4(ss)18.9(iu)18.8(m)-271.4(i)0(n)-254.3(C)0(F)17.3(B)0(E)18.1(4)0(1)15.5(o)0(-)-259.2(c)0(e)20.4(l)0(l)16.5(s)0(,)-258.4(b)0(u)21.2(t)0(,)-259.6(a)0(f)19.2(t)0(e)18.4(r)]TJ 0 -1.0755 TD [(in)13.2(cu)20.8(ba)15.1(ti)16.5(on)-576.3(wi)14.9(th)-578.7(4P)16.3(BA)18.3(,)-592.2(8)0(-)19.6(b)0(r)14(o)0(m)18.1(o)0(-)19.6(c)0(A)16.9(M)0(P)-583.1(c)0(a)20.4(u)0(s)14.4(e)0(d)-582.4(a)-587.3(si)17.7(g-)]TJ 0 -1.0698 TD [(ni)13.2(fi)17.3(ca)20.4(nt)-248.6(de)20.8(cr)13.5(ea)20.4(se)-247.8(in)-248.6(th)18.9(e)-257.2(c)0(h)20.8(l)0(o)18.9(r)0(i)17.3(n)0(e)-246.6(c)0(o)15.1(n)0(t)18.8(e)0(n)15.1(t)-253.5(\(f)18(ig)18.9(.)-256.5(1\).)-259.6(An)-267.2(X-ray)]TJ 0 -1.0755 TD [(spect)-8.2(rum)-280.2(of)-276.3(the)-272.5(cell)-8.6(s)-275.1(i)0(s)-272.6(show)-8.2(n)-273.9(i)0(n)-271.4(figur)-9.4(e)-274.3(2)0(.)-274.3(Stimulation)-284.8(of)]TJ 0 -1.0698 TD [(cell)-8.6(s)-235.3(with)-239.4(a)-234.5(combinati)-12.3(on)-234.8(of)-236.4(genistein)-243.6(and)-236(8-brom)-10.9(o-cAMP)]TJ 0 -1.0755 TD [(reduced)-486.2(the)-477.4(chlor)-8.2(ine)-477.4(conten)-7.8(t)-475.5(o)0(f)-475.4(the)-483.1(cells,)-477.6(and)-480.7(a)-473.5(com-)]TJ 0 -1.0698 TD [(binat)-9(ion)-266.4(of)-270.6(pretr)-9.8(eatment)-276.2(with)-267.8(4P)-6.4(BA)-266.3(and)-270.2(stimul)-10.4(ation)-270.7(with)]TJ 0 -1.0755 TD [(gen)-8.4(istein)-309.2(and)-304.3(cAMP)-310.2(together)-309.2(induce)-7.8(d)-302.4(a)0(n)-303.5(even)-305.5(larger)-301.2(de-)]TJ 0 -1.0698 TD [(crease)-549.6(in)-538.8(chlor)-8.2(ine)-540(conten)-7.8(t)-538.1(\(fig.)-543.9(3\).)-538.4(CPX)-545.1(signifi)-9.6(cantly)]TJ 0 -1.0755 TD [(reduced)-355.3(the)-352.2(chlorine)-354.7(content)-352.3(but)-346.1(4PBA)-352.3(did)-346.1(not)-351.8(enhance)]TJ 0 -1.0698 TD [(this)-435.8(effect)-426.8(\(fig.)-430.1(4\).)-430.3(The)-433.6(chlorine)-434.4(conten)-7.8(t)-429.9(o)0(f)-429.9(the)-431.9(control)]TJ 0 -1.0755 TD [(cell)-8.6(s)-297.9(was)-298(stabl)-10.2(e)-297.1(for)]TJ /F11 1 Tf 7.9952 0 TD ($)Tj /F7 1 Tf 0.8308 0 TD [(15)-297.4(min)-7.8(.)-296.3(The)-297(d)-6.5(ata)-295.7(for)-301.4(phospho)-6.5(rous,)]TJ -8.826 -1.0698 TD [(an)-451.5(elem)-9.4(ent)-448.9(for)-455(which)-454.4(no)-451.1(signifi)-9.6(cant)-450.1(changes)-457.3(were)-453.3(ex-)]TJ 0 -1.0755 TD [(pec)-8.8(ted,)-335.5(are)-334.7(provi)-7.8(ded)-332.8(a)-6.9(s)-332(an)-332("i)-6.9(nternal)-342.6(control".)]TJ 1.0015 -1.0471 TD [(In)-247.8(or)14(de)20.8(r)-252.7(t)0(o)-248.6(d)0(e)15.1(t)13.9(er)13.5(mi)15.7(ne)-246.6(w)12.4(h)0(e)15.1(t)0(h)18.9(e)0(r)-248.2(t)0(h)18.9(e)-257.2(se)19.6(cr)19.2(et)12.8(i)13.9(o)0(n)-246.2(o)0(f)-247.8(C)0(l)]TJ 7.472 0 0 6.641 509.386 351.269 Tm (-)Tj 9.963 0 0 9.963 514.318 346.847 Tm [(in)-242.9(CF)]TJ -20.577 -1.0755 TD [(ce)14.7(ll)16.5(s)-303.6(i)0(s)-289.6(o)0(f)-293.3(p)0(h)15.5(y)0(s)20(i)0(o)13.2(l)13.9(og)15.5(ic)18.4(al)-294.5(re)13.5(l)13.9(e)0(v)15.1(a)0(n)15.1(c)0(e)20.4(,)-302(a)-302.8(n)0(o)15.5(r)0(m)16.5(a)0(l)-294.5(h)0(u)21.2(m)0(a)17.7(n)-302.4(br)13.9(on)21.2(-)]TJ 0 -1.0698 TD [(ch)15.1(ia)18.4(l)-208(e)0(p)15.1(i)0(t)16.5(h)0(e)20.8(l)0(i)16.5(a)0(l)-203.5(c)0(e)20.4(l)0(l)-205.5(l)0(i)22.2(n)0(e)-201.1(e)0(x)15.1(p)0(r)19.6(e)0(s)13.9(s)0(i)17.7(n)0(g)-200.7(t)0(h)18.9(e)-211.7(C)11.6(F)0(T)17.9(R)0(,)-199.3(1)0(6)15.5(H)0(B)18.3(E)0(1)17.1(4)0(o)15.5(-)0(,)]TJ 0 -1.0755 TD [(wa)16.9(s)-235.3(s)0(t)17.7(i)0(m)15.7(u)0(l)18.9(a)0(t)18.5(e)0(d)-223.9(w)0(i)14.9(t)0(h)-220.2(8)0(-)19.6(b)0(r)13.9(o)0(m)18.1(o)0(-)19.6(c)0(A)16.9(M)0(P)-224.6(\()0(f)18(i)0(g)13.2(.)-228(5\).)-236.8(The)-240.1(decreas)-9.7(e)]TJ ET 0 0 0 1 K 0 J 0 j 0.5 w 2.613 M []0 d 1 i 342.095 774.2 m 342.095 649.672 l 342.359 756.488 m 339.618 756.488 l 342.359 738.441 m 339.618 738.441 l 342.359 721.153 m 339.618 721.153 l 342.359 703.106 m 339.618 703.106 l 342.359 685.608 m 339.618 685.608 l 342.359 667.58 m 339.618 667.58 l 535.038 649.85 m 339.618 649.85 l S BT /F16 1 Tf 10 0 0 10 333.4 645.195 Tm 0 0 0 1 k (0)Tj 3.8704 -0.9027 TD (P)Tj -4.3079 2.6604 TD (20)Tj 0 1.8128 TD (40)Tj 0 1.7415 TD (60)Tj 0 1.7952 TD (80)Tj -0.4625 1.7345 TD (100)Tj 0 1.8017 TD (120)Tj ET q 366.726 745.148 15.591 -95.229 re W* n 0.36 w 439.988 700.335 m 371.724 632.071 l 437.188 703.135 m 368.923 634.871 l 434.387 705.935 m 366.123 637.671 l 431.587 708.735 m 363.323 640.471 l 428.787 711.536 m 360.523 643.271 l 425.987 714.336 m 357.723 646.072 l 423.187 717.136 m 354.923 648.872 l 420.387 719.936 m 352.123 651.672 l 417.587 722.736 m 349.323 654.472 l 414.787 725.536 m 346.522 657.272 l 411.986 728.336 m 343.722 660.072 l 409.186 731.136 m 340.922 662.872 l 406.386 733.937 m 338.122 665.672 l 403.586 736.737 m 335.322 668.473 l 400.786 739.537 m 332.522 671.273 l 397.986 742.337 m 329.722 674.073 l 395.186 745.137 m 326.922 676.873 l 392.386 747.937 m 324.121 679.673 l 389.585 750.737 m 321.321 682.473 l 386.785 753.537 m 318.521 685.273 l 383.985 756.338 m 315.721 688.074 l 381.185 759.138 m 312.921 690.874 l 378.385 761.938 m 310.121 693.674 l 375.585 764.738 m 307.321 696.474 l 372.785 767.538 m 304.521 699.274 l S Q 366.726 745.148 15.591 -95.229 re S 0 0 0 0 k 351.075 727.329 15.59 -77.41 re B* q 382.316 737.569 15.591 -87.65 re W* n BT /T1 1 Tf 3.6 0 0 3.6 382.3 649.907 Tm 0 0 0 1 k (aaaaa)Tj 0 1 TD (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj 0 -24 TD (bbbbb)Tj 0 1 TD (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj ET Q 382.316 737.569 15.591 -87.65 re S q 431.293 746.796 15.59 -96.877 re W* n 0.36 w 505.683 701.163 m 436.271 631.751 l 502.883 703.963 m 433.471 634.552 l 500.083 706.763 m 430.671 637.352 l 497.282 709.563 m 427.871 640.152 l 494.482 712.364 m 425.071 642.952 l 491.682 715.164 m 422.271 645.752 l 488.882 717.964 m 419.47 648.552 l 486.082 720.764 m 416.67 651.352 l 483.282 723.564 m 413.87 654.152 l 480.482 726.364 m 411.07 656.953 l 477.682 729.164 m 408.27 659.753 l 474.881 731.964 m 405.47 662.553 l 472.081 734.765 m 402.67 665.353 l 469.281 737.565 m 399.87 668.153 l 466.481 740.365 m 397.069 670.953 l 463.681 743.165 m 394.269 673.753 l 460.881 745.965 m 391.469 676.553 l 458.081 748.765 m 388.669 679.354 l 455.281 751.565 m 385.869 682.154 l 452.48 754.365 m 383.069 684.954 l 449.68 757.166 m 380.269 687.754 l 446.88 759.966 m 377.469 690.554 l 444.08 762.766 m 374.668 693.354 l 441.28 765.566 m 371.868 696.154 l 438.48 768.366 m 369.068 698.955 l S Q 431.293 746.796 15.59 -96.877 re S 415.641 736.851 15.59 -86.932 re B* q 446.882 726.344 15.591 -76.426 re W* n BT /T2 1 Tf 3.6 0 0 3.6 446.811 649.907 Tm 0 0 0 1 k (aaaaa)Tj 0 1 TD (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj 0 -21 TD (bbbbb)Tj 0 1 TD (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj ET Q 446.882 726.344 15.591 -76.426 re S q 495.828 751.965 15.59 -102.046 re W* n 0.36 w 573.859 703.755 m 500.819 630.714 l 571.059 706.555 m 498.019 633.515 l 568.259 709.355 m 495.219 636.315 l 565.459 712.155 m 492.419 639.115 l 562.659 714.956 m 489.618 641.915 l 559.859 717.756 m 486.818 644.715 l 557.059 720.556 m 484.018 647.515 l 554.259 723.356 m 481.218 650.315 l 551.458 726.156 m 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[(F5)16.3(08)-388.5(CF)17.3(TR)-391.6(mu)12.4(t)13.9(a)0(t)12.8(i)0(o)18.9(n)0(.)-388.1(T)0(h)17.1(i)0(s)-392.1(i)0(s)-392.1(c)0(o)20.8(n)0(s)20(i)0(s)17.7(t)0(e)12.8(n)0(t)]TJ -6.362 -1.0471 TD [(wi)14.9(th)-214.5(pr)19.6(ev)15.1(io)18.9(us)-213.3(re)13.5(su)20(lt)16.5(s)-223.9(w)0(i)20.6(t)0(h)-220.2(a)0(n)20.8(o)0(t)18.9(h)0(e)15.1(r)-224.3(C)11.6(F)-227.6(ce)20.4(ll)-216.8(li)16.5(ne)-212.5(an)15.1(d)-222.7(p)0(r)19.6(i)0(m)15.7(a)0(r)13.5(y)]TJ 25.1977 23.0809 TD [(CF)-318.4(ep)20.8(it)16.5(he)15.1(li)16.5(al)-311.6(ce)14.7(ll)-313.6(cu)15.1(lt)22.2(ur)13.9(es)-316.1([5)19.6(].)-332.8(The)-336.9(effect)-330(of)-333.2(the)-340.8(xanthine)]TJ 0 -1.0755 TD [(CPX)-271.9(and)-264.5(the)-261.2(isof)-8.2(lavone)-269.5(genistein)-272.1(on)-263.3(the)-261.2(CF)-267.2(cell)-264.7(line)-270(was)]TJ T* [(inves)-7.8(tigated)-366.1(and)-361.2(this)-367.5(treatmen)-11.1(t)-356(c)-6.9(ombined)-364.1(with)-364.6(4PBA)-363.7(to)]TJ T* [(see)-499.4(whether)-503.4(the)-494.5(e)-6.9(f)0(f)12.4(ect)-500.6(of)-492.5(4P)-6.4(BA)-493.9(could)-501.7(be)-497(further)-502.3(im-)]TJ T* (proved.)Tj 1.0015 -1.0527 TD [(CP)11.6(X)-357.5(i)0(n)18.9(d)0(u)21.2(c)0(e)14.7(d)-359.3(C)11.6(l)]TJ 7.472 0 0 6.641 385.512 511.823 Tm (-)Tj 9.963 0 0 9.963 391.464 507.345 Tm [(se)14(cr)19.2(et)18.5(io)18.9(n)-359.3(i)0(n)-351(t)13.9(he)-349.1(CF)17.3(BE)12.4(41)21.2(o-)-350.2(ce)20.4(ll)-353.4(li)22.2(ne)15.1(,)]TJ -8.2456 -1.0698 TD [(wh)17.3(ic)12.8(h)-296.7(i)0(s)-289.6(c)0(o)15.1(n)0(s)20(i)0(s)17.7(t)0(e)18.4(n)0(t)-294.1(w)0(i)20.6(t)0(h)-294.1(p)0(r)19.6(e)0(v)15.1(i)0(o)18.8(u)0(s)-287.2(s)0(t)17.7(u)0(d)15.5(i)0(e)18.5(s)-297.9(on)-291.7(CF)-290(ce)14.7(ll)-290.8(li)16.5(ne)20.8(s)]TJ 0 -1.0755 TD [([1)13.9(3],)-350.6(but)-368.9(an)-360.4(incre)-8.6(ase)-362.8(of)-367.3(this)-361.8(effect)-358.5(after)-368.7(incuba)-7.8(tion)-366.3(with)]TJ T* [(4P)-6.4(BA)-209.4(was)-292.3(not)-294.9(seen)-295.3(in)-288.4(the)-295.3(presen)-8.2(t)-287.7(study)55.2(.)-290.6(The)-291.3(mecha)-8.2(nism)]TJ T* [(by)-320.2(which)-317.8(CPX)-317.4(acti)-8.6(vates)-315.5(Cl)]TJ 7.472 0 0 6.641 419.131 468.964 Tm (-)Tj 9.963 0 0 9.963 424.687 464.542 Tm [(efflux)-312.2(is)-318.1(not)-312(clear)42.2(.)-313.4(CPX)-317.4(has)]TJ -11.5803 -1.0755 TD [(bee)-8.8(n)-256.8(show)-8.2(n)-256.8(t)0(o)-260(b)-6.5(ind)-260.7(to)-260(the)-261.2(firs)-9.8(t)-259.2(nucleo)-7.8(tide-bind)-10.3(ing)-260.8(fold)-263.1(in)]TJ /F2 1 Tf T* (D)Tj /F7 1 Tf 0.6715 0 TD [(F508)-377.8(CFTR)-385.7([1)25.3(1].)-379.1(Other)-382(studi)-9.8(es)-378.7(argue)-376.1(against)-382(a)-382.4(direct)]TJ -0.6715 -1.0755 TD [(acti)-8.6(vation)-436.5(of)-435.6(CFTR)-436.9([14])-433(a)-6.9(n)0(d)-428.3(sugges)-7.4(t)-435.6(that)-435(the)-431.9(CPX)-10.2(-in-)]TJ T* [(duc)-8.4(ed)-411.7(Cl)]TJ 7.472 0 0 6.641 346.507 426.104 Tm (-)Tj 9.963 0 0 9.963 353.027 421.682 Tm [(efflux)-408.9(is)-414.8(related)-422.6(to)-413.6(CPX)-419.9(induced)-418.2(changes)-417.5(in)]TJ -4.3874 -1.0755 TD [(intr)-9.4(acellular)-233.5(pH)-233.1([14,)-226.2(15].)-231.9(Since)-228.1(4)-6.5(PBA)-226.4(did)-232.3(not)-226.6(incre)-8.6(ase)-226.2(the)]TJ T* [(effect)-392.6(of)-390.1(CPX,)-397.5(the)-392(presen)-8.2(t)-390.1(data)-393.2(do)-394.2(not)-391.6(suppor)-7.4(t)-390.1(a)-393.8(direct)]TJ T* [(effect)-335.7(of)-333.2(CPX)-340.2(on)]TJ /F2 1 Tf 7.3237 0 TD (D)Tj /F7 1 Tf 0.6715 0 TD [(F508)-332.3(CFTR)-10.1(.)]TJ -6.9937 -1.0471 TD [(Ge)11.2(ni)18.9(st)17.7(ei)18.4(n)-592.6(p)0(o)15.5(t)0(e)18.4(n)0(t)18.9(i)0(a)12.8(t)0(e)18.4(s)-593.8(cA)16.9(MP)14.4(-d)19.6(ep)15.1(en)20.8(de)15.1(nt)-584.3(ac)14.7(ti)16.5(va)20.8(ti)16.5(on)-587.7(of)]TJ /F2 1 Tf -1.0015 -1.0755 TD (D)Tj /F7 1 Tf 0.6601 0 TD [(F)11.4(5)0(0)15.5(8)-359.3(C)11.6(F)0(T)17.9(R)-364([8)19.6(].)-366.9(The)-371(presen)-8.2(t)-367.3(resul)-9.4(ts)-369.3(confirm)-373(that)-372.4(gen-)]TJ -0.6601 -1.0755 TD [(ist)-8.2(ein)-323.7(induce)-7.8(s)-326.3(the)-329.4(cAMP)-8.6(-depend)-7.7(ent)-323.7(a)-6.9(ctivation)-330.2(of)]TJ /F2 1 Tf 20.0763 0 TD (D)Tj /F7 1 Tf 0.6715 0 TD (F508)Tj ET 0 0 0 1 K 0 J 0 j 0.5 w 2.613 M []0 d 1 i 119.579 733.302 m 128.079 733.302 l 123.829 730.107 m 123.829 733.409 l 264.265 736.826 m 272.765 736.826 l 268.515 734.269 m 268.515 736.933 l 248.39 731.8 m 256.89 731.8 l 252.64 729.243 m 252.64 731.906 l 232.64 735.08 m 241.14 735.08 l 236.89 731.885 m 236.89 735.187 l 200.015 720.17 m 208.516 720.17 l 204.266 718.146 m 204.266 720.276 l 168.328 733.387 m 176.828 733.387 l 172.578 730.191 m 172.578 733.493 l 91.198 774.592 m 91.198 646.737 l 91.461 756.146 m 88.72 756.146 l 91.461 737.948 m 88.72 737.948 l 91.461 719.439 m 88.72 719.439 l 91.461 701.304 m 88.72 701.304 l 91.461 682.674 m 88.72 682.674 l 91.461 664.645 m 88.72 664.645 l 284.14 646.915 m 88.72 646.915 l S BT /F16 1 Tf 10 0 0 10 82.503 642.255 Tm 0 0 0 1 k (0)Tj 3.8704 -0.9027 TD (P)Tj -4.3079 2.6604 TD (20)Tj 0 1.8128 TD (40)Tj 0 1.8549 TD (60)Tj 0 1.8126 TD (80)Tj -0.4625 1.8392 TD (100)Tj 0 1.8254 TD (120)Tj ET q 115.829 730.732 15.59 -83.749 re W* n 0.36 w 181.1 691.659 m 120.818 631.377 l 178.299 694.459 m 118.018 634.177 l 175.499 697.259 m 115.217 636.977 l 172.699 700.059 m 112.417 639.778 l 169.899 702.86 m 109.617 642.578 l 167.099 705.66 m 106.817 645.378 l 164.299 708.46 m 104.017 648.178 l 161.499 711.26 m 101.217 650.978 l 158.699 714.06 m 98.417 653.778 l 155.898 716.86 m 95.617 656.578 l 153.098 719.66 m 92.816 659.378 l 150.298 722.46 m 90.016 662.179 l 147.498 725.261 m 87.216 664.979 l 144.698 728.061 m 84.416 667.779 l 141.898 730.861 m 81.616 670.579 l 139.098 733.661 m 78.816 673.379 l 136.298 736.461 m 76.016 676.179 l 133.497 739.261 m 73.215 678.979 l 130.697 742.061 m 70.415 681.779 l 127.897 744.862 m 67.615 684.58 l 125.097 747.662 m 64.815 687.38 l 122.297 750.462 m 62.015 690.18 l S Q 115.829 730.732 15.59 -83.749 re S q 131.418 741.982 15.59 -94.998 re W* n BT /T6 1 Tf 3.6 0 0 3.6 131.358 646.955 Tm (aaaaa)Tj 0 1 TD (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj 0 -26 TD (bbbbb)Tj 0 1 TD (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj ET Q 131.418 741.982 15.59 -94.998 re S q 180.395 726.982 15.591 -79.998 re W* n 0.36 w 243.083 689.787 m 185.401 632.106 l 240.283 692.587 m 182.601 634.906 l 237.482 695.387 m 179.801 637.706 l 234.682 698.188 m 177.001 640.506 l 231.882 700.988 m 174.201 643.306 l 229.082 703.788 m 171.401 646.106 l 226.282 706.588 m 168.601 648.906 l 223.482 709.388 m 165.8 651.707 l 220.682 712.188 m 163 654.507 l 217.882 714.988 m 160.2 657.307 l 215.081 717.788 m 157.4 660.107 l 212.281 720.589 m 154.6 662.907 l 209.481 723.389 m 151.8 665.707 l 206.681 726.189 m 149 668.507 l 203.881 728.989 m 146.2 671.307 l 201.081 731.789 m 143.399 674.108 l 198.281 734.589 m 140.599 676.908 l 195.481 737.389 m 137.799 679.708 l 192.68 740.189 m 134.999 682.508 l 189.88 742.99 m 132.199 685.308 l 187.08 745.79 m 129.399 688.108 l S Q 180.395 726.982 15.591 -79.998 re S 0 0 0 0 k 164.743 732.022 15.59 -85.039 re B* q 195.984 718.232 15.59 -71.248 re W* n BT /T7 1 Tf 3.6 0 0 3.6 195.941 646.955 Tm 0 0 0 1 k (aaaaa)Tj 0 1 TD (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj 0 -19 TD (bbbbb)Tj 0 1 TD (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj ET Q 195.984 718.232 15.59 -71.248 re S q 244.93 729.232 15.59 -82.249 re W* n 0.36 w 309.144 690.903 m 249.913 631.672 l 306.344 693.703 m 247.113 634.472 l 303.544 696.503 m 244.313 637.272 l 300.744 699.303 m 241.513 640.072 l 297.944 702.104 m 238.712 642.872 l 295.144 704.904 m 235.912 645.673 l 292.343 707.704 m 233.112 648.473 l 289.543 710.504 m 230.312 651.273 l 286.743 713.304 m 227.512 654.073 l 283.943 716.104 m 224.712 656.873 l 281.143 718.904 m 221.912 659.673 l 278.343 721.704 m 219.112 662.473 l 275.543 724.505 m 216.311 665.273 l 272.743 727.305 m 213.511 668.074 l 269.942 730.105 m 210.711 670.874 l 267.142 732.905 m 207.911 673.674 l 264.342 735.705 m 205.111 676.474 l 261.542 738.505 m 202.311 679.274 l 258.742 741.305 m 199.511 682.074 l 255.942 744.105 m 196.711 684.874 l 253.142 746.906 m 193.91 687.674 l 250.341 749.706 m 191.11 690.475 l S Q 244.93 729.232 15.59 -82.249 re S 229.278 733.232 15.59 -86.249 re B* q 260.52 734.857 15.591 -87.873 re W* n BT /T8 1 Tf 3.6 0 0 3.6 260.453 646.955 Tm 0 0 0 1 k (aaaaa)Tj 0 1 TD (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj 0 -24 TD (bbbbb)Tj 0 1 TD (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj ET Q 260.52 734.857 15.591 -87.873 re 104.146 734.783 m 112.646 734.783 l 108.396 731.588 m 108.396 734.89 l S BT /F14 1 Tf 8.521 0 0 8.521 198.463 718.916 Tm 0 0 0 1 k (***)Tj ET 123.641 646.88 m 123.641 644.544 l 188.279 646.88 m 188.279 644.544 l 252.814 646.88 m 252.814 644.544 l S BT /F16 1 Tf 10 0 0 10 184.338 633.228 Tm [(Cl)-5859.7(K)]TJ -11.084 13.6365 TD (140)Tj ET 91.461 774.482 m 88.72 774.482 l S 0 0 0 0 k 100.177 732.022 15.59 -85.039 re B* 135.079 744.956 m 143.579 744.956 l 139.328 742.16 m 139.328 745.063 l 183.953 730.161 m 192.453 730.161 l 188.203 727.285 m 188.203 730.268 l S BT /F14 1 Tf 8.521 0 0 8.521 186.529 729.022 Tm 0 0 0 1 k (*)Tj -1.8483 0.3939 TD (*)Tj /F16 1 Tf 0 10 -10 0 68.303 651.985 Tm [(Element)-228(concentr)12.7(ation)-228(%)-228(control)]TJ ET 172.23 764.982 m 204.23 764.982 l 172.23 762.232 m 172.23 765.232 l 204.23 762.232 m 204.23 765.234 l S BT /F14 1 Tf 8.521 0 0 8.521 180.757 763.772 Tm (***)Tj ET 187.983 748.727 m 204.478 748.727 l 188.239 745.977 m 188.239 748.727 l 204.23 745.977 m 204.23 748.727 l S BT 8.521 0 0 8.521 193.966 747.518 Tm (*)Tj /F7 1 Tf 7.97 0 0 7.97 58.28 618.633 Tm 0 g [(Fig.)-327.1(3.)-331.2(\261)-332.2(E)0(f)15.6(fects)-396.7(of)-401.4(4-phenylbu)12.4(tyrate)-395.8(\(4BP)91.1(A\),)-395.8(genistein)-392.9(and)-391(8-bromo-)]TJ 0 -1.0599 TD [(cyclic)-415.9(adenosine)-415.5(monopho)14.4(sphate)-415.7(\(cAMP\))-412.9(\(8-bromo-cAM)9.4(P\))-420.6(on)-415.5(phos-)]TJ 0 -1.067 TD [(phorus,)-485.6(chlorine)-484(and)-483.5(potassium)-485.4(levels)-482.1(in)-489(CFBE41o-)-484(cells.)-483.2(Data)-492.4(are)]TJ 0 -1.0599 TD [(presented)-387.2(as)-394.3(mean\213)]TJ 5.579 0 0 5.579 122.627 593.234 Tm (SEM)Tj 7.97 0 0 7.97 137.197 593.234 Tm [(from)-390.6(four)-390.3(to)-396.5(eight)-391.6(experiments)-385.7(with)-397.2(96)-394.1(mea-)]TJ -9.9015 -1.067 TD [(surements)-275.9(on)-287.5(8-bromo-c)12(AMP)-284.7(and)-284.3(genistei)10.5(n)-289.6(\()]TJ /F21 1 Tf 18.0602 0 TD (h)Tj /F7 1 Tf 0.8322 0 TD [(\),)-281.6(59)-287.5(on)-280.3(cells)-285.1(stimulated)]TJ -18.8925 -1.0599 TD [(with)-354.5(4PBA)-345.1(and)-355.5(cAMP)-352.7(\()]TJ /F12 1 Tf 9.9513 0 TD (u)Tj /F7 1 Tf 0.7967 0 TD [(\))-360.9(and)-348.3(87)-351.5(on)-351.5(cells)-356.2(stimulated)-350.7(with)-354.5(4PBA,)-344.1(8-)]TJ -10.7479 -1.0599 TD [(bromo-cAM)10.6(P)-429.6(and)-426.6(genistein)-428.4(\()]TJ /F12 1 Tf 12.1066 0 TD (r)Tj /F7 1 Tf 0.9958 0 TD [(\).)-430.9(*:)-432.1(p)]TJ /F10 1 Tf 2.703 0 TD (<)Tj /F7 1 Tf 0.5477 0 TD [(0.05;)-426.8(***:)-427.9(p)]TJ /F10 1 Tf 5.1428 0 TD (<)Tj /F7 1 Tf 0.5548 0 TD (0.001)Tj /F4 1 Tf 2.6745 0 TD (versus)Tj /F7 1 Tf 2.952 0 TD (8-)Tj -27.6772 -1.067 TD [(bromo-cAM)10.6(P)-330(o)0(r)-330.3(between)-328.6(columns)-329.6(indicated.)]TJ ET 268.207 283.818 m 268.207 287.768 l 252.333 290.317 m 252.333 294.242 l 232.333 284.416 m 240.832 284.416 l 236.583 281.22 m 236.583 284.522 l 187.895 292.067 m 187.895 296.985 l 203.958 283.318 m 203.958 287.236 l 168.075 279.222 m 176.575 279.222 l 172.325 275.699 m 172.325 279.329 l 103.838 286.643 m 112.338 286.643 l 108.088 283.448 m 108.088 286.75 l 123.521 290.317 m 123.521 294.744 l 139.021 280.317 m 139.021 284.148 l 90.89 311.297 m 90.89 183.322 l 91.154 289.409 m 88.412 289.409 l 91.154 268.32 m 88.412 268.32 l 91.154 247.29 m 88.412 247.29 l 91.154 225.865 m 88.412 225.865 l 91.154 204.851 m 88.412 204.851 l 283.832 183.501 m 88.412 183.501 l S BT /F16 1 Tf 10 0 0 10 82.195 178.836 Tm 0 0 0 1 k (0)Tj 3.8704 -0.9027 TD (P)Tj -4.3079 3.0224 TD (20)Tj 0 2.0955 TD (40)Tj 0 2.1522 TD (60)Tj 0 2.1086 TD (80)Tj -0.4625 2.0954 TD (100)Tj 0 2.1638 TD (120)Tj ET q 115.521 290.317 15.591 -106.748 re W* n 0.36 w 196.876 239.764 m 120.52 163.408 l 194.076 242.564 m 117.72 166.208 l 191.276 245.364 m 114.92 169.008 l 188.476 248.164 m 112.12 171.808 l 185.675 250.965 m 109.319 174.609 l 182.875 253.765 m 106.519 177.409 l 180.075 256.565 m 103.719 180.209 l 177.275 259.365 m 100.919 183.009 l 174.475 262.165 m 98.119 185.809 l 171.675 264.965 m 95.319 188.609 l 168.875 267.765 m 92.519 191.409 l 166.075 270.565 m 89.719 194.209 l 163.274 273.366 m 86.918 197.01 l 160.474 276.166 m 84.118 199.81 l 157.674 278.966 m 81.318 202.61 l 154.874 281.766 m 78.518 205.41 l 152.074 284.566 m 75.718 208.21 l 149.274 287.366 m 72.918 211.01 l 146.474 290.166 m 70.118 213.81 l 143.673 292.966 m 67.317 216.61 l 140.873 295.767 m 64.517 219.411 l 138.073 298.567 m 61.717 222.211 l 135.273 301.367 m 58.917 225.011 l 132.473 304.167 m 56.117 227.811 l 129.673 306.967 m 53.317 230.611 l 126.873 309.767 m 50.517 233.411 l 124.073 312.567 m 47.717 236.211 l 121.272 315.367 m 44.916 239.011 l S Q 115.521 290.317 15.591 -106.748 re S 0 0 0 0 k 99.869 284.317 15.59 -100.748 re B* q 131.11 280.317 15.591 -96.748 re W* n BT /T9 1 Tf 3.6 0 0 3.6 131.06 183.54 Tm 0 0 0 1 k (aaaaa)Tj 0 1 TD (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj 0 -26 TD (bbbbb)Tj 0 1 TD (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj ET Q 131.11 280.317 15.591 -96.748 re S q 180.087 292.818 15.591 -109.248 re W* n 0.36 w 263.144 240.988 m 185.068 162.912 l 260.344 243.788 m 182.267 165.712 l 257.544 246.588 m 179.467 168.512 l 254.744 249.388 m 176.667 171.312 l 251.943 252.189 m 173.867 174.112 l 249.143 254.989 m 171.067 176.912 l 246.343 257.789 m 168.267 179.712 l 243.543 260.589 m 165.467 182.513 l 240.743 263.389 m 162.667 185.313 l 237.943 266.189 m 159.866 188.113 l 235.143 268.989 m 157.066 190.913 l 232.343 271.789 m 154.266 193.713 l 229.542 274.59 m 151.466 196.513 l 226.742 277.39 m 148.666 199.313 l 223.942 280.19 m 145.866 202.113 l 221.142 282.99 m 143.066 204.914 l 218.342 285.79 m 140.266 207.714 l 215.542 288.59 m 137.465 210.514 l 212.742 291.39 m 134.665 213.314 l 209.942 294.19 m 131.865 216.114 l 207.141 296.991 m 129.065 218.914 l 204.341 299.791 m 126.265 221.714 l 201.541 302.591 m 123.465 224.514 l 198.741 305.391 m 120.665 227.315 l 195.941 308.191 m 117.865 230.115 l 193.141 310.991 m 115.064 232.915 l 190.341 313.791 m 112.264 235.715 l 187.541 316.591 m 109.464 238.515 l S Q 180.087 292.818 15.591 -109.248 re S 164.49 275.567 15.59 -91.998 re B* q 195.677 283.568 15.59 -99.998 re W* n BT /T10 1 Tf 3.6 0 0 3.6 195.644 183.54 Tm 0 0 0 1 k (aaaaa)Tj 0 1 TD (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj 0 -27 TD (bbbbb)Tj 0 1 TD (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj ET Q 195.677 283.568 15.59 -99.998 re S q 244.623 290.567 15.59 -106.998 re W* n 0.36 w 326.122 239.872 m 249.615 163.365 l 323.322 242.672 m 246.815 166.165 l 320.522 245.472 m 244.015 168.965 l 317.722 248.272 m 241.215 171.765 l 314.922 251.073 m 238.415 174.565 l 312.122 253.873 m 235.615 177.366 l 309.322 256.673 m 232.814 180.166 l 306.521 259.473 m 230.014 182.966 l 303.721 262.273 m 227.214 185.766 l 300.921 265.073 m 224.414 188.566 l 298.121 267.873 m 221.614 191.366 l 295.321 270.673 m 218.814 194.166 l 292.521 273.474 m 216.014 196.966 l 289.721 276.274 m 213.214 199.767 l 286.921 279.074 m 210.413 202.567 l 284.12 281.874 m 207.613 205.367 l 281.32 284.674 m 204.813 208.167 l 278.52 287.474 m 202.013 210.967 l 275.72 290.274 m 199.213 213.767 l 272.92 293.074 m 196.413 216.567 l 270.12 295.875 m 193.613 219.367 l 267.32 298.675 m 190.813 222.168 l 264.52 301.475 m 188.012 224.968 l 261.719 304.275 m 185.212 227.768 l 258.919 307.075 m 182.412 230.568 l 256.119 309.875 m 179.612 233.368 l 253.319 312.675 m 176.812 236.168 l 250.519 315.475 m 174.012 238.968 l S Q 244.623 290.567 15.59 -106.998 re S 228.971 282.317 15.59 -98.748 re B* q 260.212 284.317 15.59 -100.748 re W* n BT /T11 1 Tf 3.6 0 0 3.6 260.155 183.54 Tm 0 0 0 1 k (aaaaa)Tj 0 1 TD (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj T* (aaaaa)Tj 0 -28 TD (bbbbb)Tj 0 1 TD (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj T* (bbbbb)Tj ET Q 260.212 284.317 15.59 -100.748 re 263.957 287.661 m 272.457 287.661 l 248.083 294.135 m 256.583 294.135 l 119.271 294.637 m 127.771 294.637 l S BT /F14 1 Tf 8.521 0 0 8.521 170.52 278.674 Tm 0 0 0 1 k (*)Tj ET 123.334 183.465 m 123.334 181.129 l 187.971 183.465 m 187.971 181.129 l 252.506 183.465 m 252.506 181.129 l S BT /F16 1 Tf 10 0 0 10 184.03 169.809 Tm [(Cl)-5859.7(K)]TJ ET 91.154 311.067 m 88.412 311.067 l 134.771 284.042 m 143.271 284.042 l 183.646 296.879 m 192.145 296.879 l 199.708 287.13 m 208.208 287.13 l S BT 0 10 -10 0 68.861 188.07 Tm [(Element)-228(concentr)12.7(ation)-228(%)-228(control)]TJ /F7 1 Tf 7.97 0 0 7.97 58.28 155.225 Tm 0 g [(Fig.)-327.1(4.)-331.2(\261)-332.2(E)0(f)15.6(fects)-389.6(of)-394.3(8-cyclopentyl-)10.8(1,3)]TJ /F10 1 Tf 15.1794 0 TD (=)Tj /F7 1 Tf 0.5548 0 TD [(dipropyl)11.9(xanthine)-384.3(\(CPX\))-393.2(and)-383.9(4-)]TJ -15.7343 -1.067 TD [(phenylbutyr)12.1(ate)-563.1(\(4PBA\))-554.7(on)-557.8(CFBE41o-)-555.2(cells.)-554.3(Data)-563.5(are)-560.9(presented)-550.8(as)]TJ 0 -1.0599 TD (mean\213)Tj 5.579 0 0 5.579 79.654 138.274 Tm (SEM)Tj 7.97 0 0 7.97 95.187 138.274 Tm [(from)-525.8(four)-518.3(to)-517.5(six)-523.7(experiment)11.7(s)-525.5(with)-518.1(43)-522.2(measurement)8.7(s)-518.4(o)0(n)]TJ -4.6306 -1.0599 TD [(control)-316.4(cells,)-326.7(60)-323(on)-315.9(cells)-327.8(stimulate)9.9(d)-325.1(with)-319(CPX)-325.9(\()]TJ /F21 1 Tf 19.3406 0 TD (h)Tj /F7 1 Tf 0.8322 0 TD [(\),)-324.2(43)-315.9(on)-323(cells)-320.6(treated)]TJ -20.1728 -1.067 TD [(with)-276.3(4BP)89.2(A)-270.7(and)-277.2(38)-266.1(on)-273.2(cells)-278(treated)-271.7(with)-269.2(4BP)82(A)-270.7(and)-270.1(CPX)-276.1(\()]TJ /F12 1 Tf 22.8189 0 TD (r)Tj /F7 1 Tf 0.9958 0 TD [(\).)-274.4(*:)-275.6(p)]TJ /F10 1 Tf 2.39 0 TD (<)Tj /F7 1 Tf 0.5477 0 TD (0.05)Tj /F4 1 Tf -26.7525 -1.0599 TD (versus)Tj /F7 1 Tf 2.8595 0 TD (control.)Tj ET 0.5 w 3.864 M /GS3 gs 341.367 773.131 m 341.367 645.623 l 341.631 772.939 m 338.889 772.939 l 341.631 751.76 m 338.889 751.76 l 341.631 730.582 m 338.889 730.582 l 341.631 709.403 m 338.889 709.403 l 341.631 688.225 m 338.889 688.225 l 341.631 667.046 m 338.889 667.046 l 537.244 645.868 m 338.889 645.868 l S BT /F20 1 Tf 10 0 0 10 332.672 642.331 Tm 0 0 0 1 k /GS4 gs (0)Tj -0.4468 2.1022 TD (20)Tj T* (40)Tj 0 2.1187 TD (60)Tj 0 2.1129 TD (80)Tj -0.4468 2.1352 TD (100)Tj 0 2.1518 TD (120)Tj ET /GS3 gs 367.283 751.703 m 391.888 751.703 l 379.349 748.979 m 379.349 751.854 l 429.921 728.914 m 454.526 728.914 l 441.987 724.071 m 441.987 729.065 l 492.105 745.216 m 516.71 745.216 l 504.17 742.644 m 504.17 745.368 l S BT /F25 1 Tf 10 0 0 10 501.618 749.756 Tm /GS4 gs (*)Tj -6.8388 -1.8875 TD 0.1184 Tc [(**)13.1(*)]TJ /F20 1 Tf -5.6559 -9.805 TD 5.5762 Tc [(PC)5576.2(l)-76.6(K)]TJ 0 10 -10 0 319.136 650.367 Tm 0 Tc [(Element concentr)10(ation % control)]TJ ET 0 0 0 0 k /GS3 gs 355.369 748.972 48.243 -103.072 re B 418.118 724.131 48.197 -78.231 re B 480.118 742.631 48.197 -96.731 re B BT /F7 1 Tf 7.97 0 0 7.97 309.316 617.556 Tm 0 g /GS2 gs [(Fig.)-334.3(5.)-324.1(\261)-332.2(Effe)13.5(cts)-728.9(of)-728.6(8-bromo-c)12(yclic)-732(adenosine)-714.3(monophosphat)15.3(e)-729.6(\(8-)]TJ 0 -1.0599 TD [(bromo-cAM)10.6(P\))-385(on)-379.9(16HBE14o-)-375.2(cells.)-383.6(Data)-378.6(are)-383.1(presented)-380.1(as)-380.1(mean\213)]TJ 5.579 0 0 5.579 525.09 609.109 Tm (SEM)Tj 7.97 0 0 7.97 309.316 600.605 Tm [(from)-219.9(three)-210.5(experiments)-215(with)-212.3(26)-216.3(measurem)10.8(ents)-214.7(on)-216.3(control)-216.8(cells)-213.9(and)-213.2(48)-216.3(on)]TJ T* [(8-bromo-cAMP)11.8(-stimulated)-711.6(cells.)-710.8(*:)-716.6(p)]TJ /F10 1 Tf 16.2037 0 TD (<)Tj /F7 1 Tf 0.5548 0 TD [(0.05;)-711.4(***:)-712.4(p)]TJ /F10 1 Tf 5.7118 0 TD (<)Tj /F7 1 Tf 0.5477 0 TD (0.001)Tj /F4 1 Tf 2.9591 0 TD (versus)Tj /F7 1 Tf -25.9772 -1.0599 TD (control.)Tj ET 0.5 w 2.613 M 389.587 254.049 m 389.587 256.299 l 340.393 326.299 m 340.393 198.792 l 340.657 326.107 m 337.915 326.107 l 340.657 304.929 m 337.915 304.929 l 340.657 283.75 m 337.915 283.75 l 340.657 262.571 m 337.915 262.571 l 340.657 241.393 m 337.915 241.393 l 340.657 220.215 m 337.915 220.215 l 534.836 199.037 m 337.915 199.037 l S BT /F27 1 Tf 10 0 0 10 331.698 194.283 Tm 0 0 0 1 k (0)Tj 0 2.1295 TD (5)Tj -0.4498 2.0776 TD (10)Tj 0 2.1295 TD (15)Tj 0 2.1254 TD (20)Tj 0 2.1295 TD (25)Tj 0 2.1136 TD (30)Tj ET 0 0 0 0 k 345.056 211.444 25.946 -12.385 re B* 376.306 254.049 25.531 -54.99 re B* 407.806 228.8 25.53 -29.741 re B* 438.805 262.049 25.781 -62.99 re B* 470.055 291.799 25.781 -92.74 re B* q 501.305 309.049 26.031 -109.99 re W* n 0.36 w 591.512 256.844 m 511.517 176.849 l 588.712 259.645 m 508.717 179.649 l 585.912 262.445 m 505.917 182.449 l 583.112 265.245 m 503.117 185.249 l 580.312 268.045 m 500.316 188.049 l 577.512 270.845 m 497.516 190.85 l 574.712 273.645 m 494.716 193.65 l 571.912 276.445 m 491.916 196.45 l 569.111 279.245 m 489.116 199.25 l 566.311 282.046 m 486.316 202.05 l 563.511 284.846 m 483.516 204.85 l 560.711 287.646 m 480.716 207.65 l 557.911 290.446 m 477.915 210.45 l 555.111 293.246 m 475.115 213.251 l 552.311 296.046 m 472.315 216.051 l 549.51 298.846 m 469.515 218.851 l 546.71 301.647 m 466.715 221.651 l 543.91 304.447 m 463.915 224.451 l 541.11 307.247 m 461.115 227.251 l 538.31 310.047 m 458.315 230.051 l 535.51 312.847 m 455.514 232.852 l 532.71 315.647 m 452.714 235.652 l 529.91 318.447 m 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[(de)15.1(cr)19.2(ea)20.4(se)-355.9(in)-356.7(C)11.6(l)]TJ 7.472 0 0 6.641 115.427 535.464 Tm (-)Tj 9.963 0 0 9.963 121.436 531.042 Tm [(in)-356.7(th)18.9(e)-365.4(n)0(o)21.2(r)0(m)16.5(a)0(l)-357.1(c)0(e)20.4(l)0(l)16.5(s)-366.2(ex)20.8(pr)14(es)19.6(si)17.7(ng)-354.3(th)18.9(e)-365.4(C)11.6(FT)17.9(R)]TJ -6.3393 -1.0527 TD [(af)19.2(te)12.8(r)-252.7(8)0(-)19.6(b)0(r)13.9(o)0(m)18.1(o)0(-)19.6(c)0(A)16.9(M)0(P)-247.4(s)0(t)17.7(i)0(m)15.7(u)0(l)18.9(a)0(t)12.8(i)0(o)18.9(n)-251.2(is)-249.8(th)18.9(er)19.2(ef)13.5(or)19.6(e)-257.2(e)0(q)20.8(u)0(i)18.9(v)0(a)15.1(l)0(e)18.4(n)0(t)-248.6(t)0(o)]TJ 0 -1.0471 TD 0.2174 Tc [(a1)217.4(2)11(m)217.4(M)5.9(d)217.4(e)238.2(c)217.4(r)236.6(e)217.4(a)232.1(s)217.4(e)9.4(i)217.4(n)8.6(C)229(l)]TJ 7.472 0 0 6.641 149.613 514.545 Tm 0 Tc (-)Tj 9.963 0 0 9.963 151.937 510.123 Tm 0.2166 Tc [(.I)216.6(t)11.9(i)216.6(s)6.6(e)216.6(x)237.4(p)216.6(e)231.7(c)216.6(t)235(e)216.6(d)9.8(t)216.6(h)235.5(a)216.6(t)7.4(C)216.6(l)]TJ 7.472 0 0 6.641 235.502 514.545 Tm 0 Tc (-)Tj 9.963 0 0 9.963 240.038 510.123 Tm [(ef)24.9(fl)17.3(ux)-206.4(is)-204.3(ac)14.7(-)]TJ -18.2439 -1.0528 TD [(co)15.1(mp)18.1(an)20.8(ie)12.8(d)-245.5(b)0(y)-234.8(K)]TJ 7.472 0 0 6.641 122.797 504.057 Tm (+)Tj 9.963 0 0 9.963 129.43 499.634 Tm [(ef)30.6(fl)17.3(ux)15.5(.)-245.1(I)0(n)-236.4(a)0(l)18.4(l)-247.8(ex)20.8(pe)15.1(ri)17.3(me)17.7(nt)18.9(s,)-241.3(th)18.9(e)-245.9(p)0(o)21.2(t)0(a)12.8(s)0(s)18.9(i)0(u)18.8(m)]TJ -7.1416 -1.0527 TD [(co)15.1(nc)20.8(en)15.1(tr)17.3(at)18.5(io)18.9(ns)-401.1(i)13.9(n)-410.5(th)18.9(e)-405.2(c)0(e)14.7(l)0(l)16.5(s)-406(th)18.9(at)-397(sh)14.4(ow)-398.1(ch)20.8(lo)18.9(ri)11.6(de)-394.6(ef)24.9(fl)17.3(ux)-394.2(ar)13.5(e)]TJ 0 -1.0471 TD [(lo)18.9(we)16.9(r)-406.4(t)0(h)18.9(a)0(n)-394.6(i)0(n)-390.9(t)0(h)18.9(e)-405.2(co)15.1(nt)18.9(ro)19.6(l)-401.5(c)0(e)14.7(l)0(l)16.5(s)-400.3(by)-394.2(~4)18.1(0\261)15.5(50)-394.2(mm)20.6(ol)]TJ /F9 1 Tf 19.8316 0.1992 TD (.)Tj /F7 1 Tf 0.2675 -0.1992 TD [(kg)-394.2(dr)13.9(y)]TJ -20.099 -1.0528 TD [(we)16.9(ig)18.8(ht)]TJ 7.472 0 0 6.641 84.643 472.649 Tm -0.0185 Tc (-1)Tj 9.963 0 0 9.963 90.595 468.227 Tm -0.0172 Tc [(,)-438.7(o)-17.2(r)-430(p)-17.2(ra)-17.2(ct)-17.2(ic)-17.2(al)-17.2(ly)-439.1(t)-17.2(h)1.7(e)-445.2(s)-17.2(am)-17.2(e)-432(a)-17.2(s)-430(t)-17.2(he)-445.2(Cl)]TJ 7.472 0 0 6.641 232.044 472.649 Tm 0 Tc (-)Tj 9.963 0 0 9.963 238.677 468.227 Tm [(ef)30.6(fl)17.3(ux)15.5(.)-421.5(T)0(h)17.1(i)0(s)]TJ -18.1073 -1.0471 TD [(me)17.7(an)15.1(s)-394.6(t)0(h)13.2(a)0(t)-385.6(t)0(h)18.9(e)0(r)13.5(e)-399.5(is)-386.4(no)-388.5(ne)15.1(ed)-388.9(to)-385.2(in)13.2(vo)21.2(ke)-388.9(me)17.7(ch)15.1(an)15.1(i)13.9(s)0(m)-392.8(o)0(t)18.9(h)0(e)15.1(r)]TJ 0 -1.0528 TD [(th)18.9(an)-258(Cl)]TJ 7.472 0 0 6.641 86.854 451.729 Tm (-)Tj 9.963 0 0 9.963 91.899 447.307 Tm [(ef)24.9(fl)17.3(ux)-257.6(ac)14.7(co)20.8(mp)18.1(an)15.1(ie)18.4(d)-268.2(b)0(y)-257.6(a)-268.6(st)17.7(oi)18.9(ch)15.1(io)18.9(me)17.7(tr)17.3(ic)-260.4(K)]TJ 7.472 0 0 6.641 255.685 451.729 Tm (+)Tj 9.963 0 0 9.963 262.545 447.307 Tm [(ef)30.6(fl)17.3(ux)]TJ -20.503 -1.0471 TD [(to)-305.5(ma)17.7(in)18.9(ta)12.8(in)-305.5(el)18.4(ec)20.4(tr)17.3(on)15.5(eu)20.8(tr)11.6(al)18.4(it)16.5(y)-313.7(a)0(n)20.8(d)-313.7(it)-307.9(is)-306.7(no)21.2(t)-316.1(n)0(e)20.8(c)0(e)14.7(s)0(s)18.9(a)0(r)19.2(y)-313.7(to)-305.5(as)13.9(-)]TJ 0 -1.0527 TD [(su)20(me)12(,)-432.9(f)0(o)19.6(r)-434.8(ex)15.1(am)17.7(pl)18.9(e,)-428.3(C)11.6(l)]TJ 7.472 0 0 6.641 149.896 430.809 Tm (-)Tj 9.963 0 0 9.963 152.22 426.387 Tm [(/b)18.9(ic)18.4(ar)13.5(bo)21.2(na)15.1(te)-425.4(ex)15.1(ch)20.8(an)15.1(ge)20.8(.)-432.9(H)0(o)17.3(w)0(e)16.9(v)0(e)15.1(r)37.5(,)]TJ -9.4292 -1.0471 TD [(th)18.9(is)-238.4(ef)24.9(fl)17.3(ux)-234.8(of)-242.1(K)]TJ 7.472 0 0 6.641 117.694 420.378 Tm (+)Tj 9.963 0 0 9.963 124.328 415.956 Tm [(is)-238.4(so)-241.7(sm)16.9(al)18.5(l)-247.8(r)0(e)19.2(l)0(a)18.4(t)0(i)16.5(v)0(e)-240.9(t)0(o)-237.2(t)0(h)18.9(e)-251.6(hi)18.9(gh)-234.8(K)]TJ 7.472 0 0 6.641 250.242 420.378 Tm (+)Tj 9.963 0 0 9.963 256.932 415.956 Tm [(co)20.8(nt)18.9(en)15.1(t)]TJ -19.9397 -1.0527 TD [(of)-276.3(th)18.9(e)-285.7(c)0(e)14.7(l)0(l)16.5(s)-280.8(\(~)16.5(5%)13.2(\))-281.2(t)0(h)13.2(a)0(t)-271.8(a)-285.7(si)17.7(gn)15.5(if)17.3(ic)18.4(an)15.1(t)-282(d)0(e)15.1(c)0(r)19.2(e)0(a)14.7(s)0(e)-276.3(i)0(n)-277.1(p)0(o)21.2(t)0(a)12.8(s)0(s)18.9(i)0(u)18.8(m)]TJ 0 -1.0471 TD [(co)15.1(nt)18.9(en)20.8(t)-412.9(c)0(o)15.1(u)0(l)18.9(d)-416.2(on)21.2(ly)-402.3(be)-406(se)19.6(en)-406(in)-407.9(t)13.9(h)0(e)-406(e)0(x)15.1(p)0(e)20.8(r)0(i)17.3(m)0(e)17.7(n)0(t)-407.9(s)0(h)20(o)0(w)17.3(n)-416.2(in)]TJ 0 -1.0528 TD [(fi)17.3(gu)15.5(re)-310.8(5.)]TJ 1.0015 -1.0527 TD [(Th)17.1(e)-223.1(e)0(f)30.6(f)0(e)19.2(c)0(t)-214.9(a)0(c)14.7(h)0(i)18.9(e)0(v)20.8(e)0(d)-212.5(b)0(y)-212.1(4)0(P)16.3(B)11.6(A,)-215.6(ge)20.8(ni)18.9(st)12(ei)18.4(n)-217(a)0(n)15.1(d)-217(CP)17.3(X)-226.6(o)0(n)-206.4(t)0(h)13.2(e)]TJ -1.0015 -1.0471 TD [(CF)-415.2(ce)20.4(ll)-416(li)16.5(ne)-411.7(wa)16.9(s)-423.1(c)0(o)15.1(m)0(p)18.1(a)0(r)19.2(e)0(d)-417.3(w)12.4(it)16.5(h)-421.9(t)0(h)18.9(e)-422.3(ef)24.9(fe)19.2(ct)-414(of)-412.8(8-)13.9(br)19.6(om)18.1(o-)]TJ 0 -1.0527 TD [(cA)16.9(MP)-310(on)-303.1(hu)15.5(ma)17.7(n)-313.7(b)0(r)13.9(o)0(n)21.2(c)0(h)15.1(i)0(a)18.4(l)-316.1(ep)15.1(i)13.9(t)0(h)13.2(e)0(l)18.4(i)0(a)18.4(l)-316.1(ce)14.7(l)13.9(l)0(s)-312.4(e)0(x)20.8(p)0(r)19.6(e)0(s)13.9(s)0(i)17.7(n)0(g)-303.1(t)0(h)13.2(e)]TJ 0 -1.0471 TD [(wi)14.9(ld)18.9(-t)17.3(yp)15.5(e)-422.3(C)11.6(FT)12.2(R)11.6(.)-421.5(W)37.9(i)0(t)16.5(h)-421.9(4P)16.3(BA)-419.9(\(1)19.6(5%)-413.6(de)15.1(cr)19.2(ea)14.7(se)19.6(\),)-418.2(ge)20.8(ni)18.9(st)17.7(ei)12.8(n)]TJ 0 -1.0527 TD [(\(7)19.6(%)-355.9(d)0(e)20.8(c)0(r)13.5(e)0(a)20.4(s)0(e)13.9(\))-349.5(an)20.8(d)-353.6(C)0(P)17.3(X)-351.8(\(1)19.6(3%)-345.3(de)15.1(cr)19.2(ea)20.4(se)13.9(\))-349.5(t)0(h)18.9(e)-354(re)19.2(du)15.5(ct)18.4(io)18.9(n)-353.6(i)0(n)]TJ 0 -1.0471 TD (Cl)Tj 7.472 0 0 6.641 67.465 326.211 Tm (-)Tj 9.963 0 0 9.963 72.397 321.789 Tm [(co)20.8(nc)15.1(en)20.8(tr)17.3(at)12.8(io)18.8(n)-251.2(i)0(n)-248.6(t)0(h)18.9(e)-257.2(ce)20.4(ll)16.5(s)-252.3(i)0(s)-249.8(l)0(e)18.4(s)0(s)-242.9(t)0(h)13.2(a)0(n)-240.9(t)0(h)13.2(e)-251.6(26)15.5(%)-253.5(d)0(e)15.1(c)0(r)19.2(e)0(a)14.7(s)0(e)]TJ -1.4169 -1.0528 TD [(ac)14.7(hi)18.9(ev)20.8(ed)-400.3(by)-405.6(cA)16.9(MP)-401(in)-396.6(th)13.2(e)-405.2(n)0(o)15.5(r)0(m)16.5(a)0(l)-402.7(c)0(e)20.4(l)0(l)16.5(s)0(.)-400.7(H)0(o)17.3(w)0(e)16.9(v)0(e)15.1(r)43.2(,)-410.1(c)0(o)15.1(m)0(-)]TJ 0 -1.0471 TD [(bi)18.9(ne)15.1(d)-228.4(t)0(r)17.3(e)0(a)14.7(t)0(m)15.7(e)0(n)20.8(t)-230.8(wi)14.9(th)-220.2(4P)16.3(BA)-220.7(an)15.1(d)-228.4(g)0(e)15.1(n)0(i)18.9(s)0(t)17.7(e)0(i)18.4(n)0(,)-223.1(w)0(i)14.9(t)0(h)-220.2(a)-228.8(re)13.5(du)21.2(ct)18.4(io)13.2(n)]TJ 0 -1.0528 TD [(in)-368.1(Cl)]TJ 7.472 0 0 6.641 78.803 294.803 Tm (-)Tj 9.963 0 0 9.963 84.983 290.381 Tm [(co)20.8(nc)15.1(en)20.8(tr)17.3(at)18.5(io)13.2(n)-376.3(o)0(f)-367.3(2)0(2)15.5(%)0(,)-367.7(i)0(s)-369.3(c)0(o)15.1(m)0(p)18.1(a)0(r)19.2(a)0(b)15.1(l)0(e)-368.5(w)0(i)14.9(t)0(h)-368.1(t)0(h)18.9(e)-376.7(de)15.1(-)]TJ -2.6802 -1.0471 TD [(cr)19.2(ea)14.7(se)-213.7(ac)14.7(hi)18.9(ev)20.8(ed)-218.2(in)-214.5(no)21.2(rm)16.5(al)-214.9(ce)14.7(ll)16.5(s)-223.9(\()0(f)18(i)0(g)18.9(.)-222.3(6\).)-225.4(Many)-238.7(groups)-240.7(have)]TJ 0 -1.0528 TD [(shown)-566.6(that)-560.2(genis)-7.8(tein)-560.2(incre)-8.6(ases)-563.9(the)-562.7(probabi)-9.7(lity)-562.2(of)-560.8(the)]TJ /F2 1 Tf T* (D)Tj /F7 1 Tf 0.6658 0 TD [(F5)-6.4(08)-439.7(CFTR)-442.6(being)-444.8(open)-441.6(and)-440.9(have)-442(sugges)-7.4(ted)-437.6(a)-439.3(direc)-8.6(t)]TJ -0.6658 -1.0471 TD [(action)-505.2(of)-498.2(genis)-7.8(tein)-497.6(on)-502.3(the)-500.2(CFTR)-499.5([7\2619].)-502.5(Geni)-9.8(stein)-499.6(in-)]TJ 0 -1.0528 TD [(creases)-318.2(the)-306.7(phospho)-6.5(rylat)-10.6(ion)-306.3(level)-316.7(of)-304.7(the)-312.4(regul)-8.2(atory)-309.8(dom-)]TJ 0 -1.0471 TD [(ain)-448.9([8,)-441.7(20])-447.7(without)-454.6(increasing)-454.6(cAMP)-446.7(level)-9.4(s)-445.8(o)0(r)-441.3(prote)-8.2(in)]TJ 0 -1.0528 TD [(kinas)-7.8(e)-274.3(A)-272.2(acti)-8.6(vity)-275.3([20,)-277.4(21].)-277.4(Furthe)-8.2(rmor)-9.4(e,)-274.7(it)-273.7(prevent)-10.1(s)-275.1(deac-)]TJ 0 -1.0471 TD [(tivatio)-9.6(n)-342.2(o)0(f)-338.9(the)-340.8(cha)-8.8(nnel)-341.6(after)-345.9(remo)-8.2(val)-340.8(of)-344.6(cAMP-ind)-9.9(ucing)]TJ 0 -1.0527 TD [(stimul)-10.4(ation)-304.9([21,)-300.2(22].)-300.2(This)-306.7(can)-299(be)-303.5(explained)-308.7(by)-297.4(inhi)-7.8(bition)]TJ 0 -1.0471 TD [(of)-401.5(the)-397.7(depho)-9.9(sphorylation)-406.4(of)-401.5(the)-403.4(regulatory)-409(domain)-403.2(that)]TJ 0 -1.0527 TD [(inactivat)-11.9(es)-532.3(the)-534.3(channel)-8.9(.)-529.6(Genist)-9.2(ein)-528.6(incre)-8.6(ases)-535.5(the)-534.3(phos-)]TJ 0 -1.0471 TD [(phoryl)-8.6(ation)-322(level)-328.1(of)-316.1(the)-323.7(CFTR)-323.1(but)-323.3(also)-325.7(increases)-327.8(the)-323.7(ac-)]TJ 0 -1.0527 TD [(tivity)-327.1(of)-316.1(the)-323.7(channel)-321.9(indepe)-7.8(ndent)-325.3(of)-316.1(the)-323.7(phospho)-6.5(rylation)]TJ T* [(level)-339.4([8].)]TJ 1.0015 -1.0471 TD [(4-)19.6(ph)15.5(en)15.1(yl)18.9(bu)21.2(ty)13.2(ra)19.2(te)-544.9(di)18.9(re)19.2(ct)18.4(s)-553.9(m)0(o)18.1(r)0(e)]TJ /F2 1 Tf 12.8606 0 TD (D)Tj /F7 1 Tf 0.6601 0 TD [(F)11.4(5)0(0)15.5(8)-552.7(cy)20.8(st)17.7(ic)-544.9(fi)17.3(br)19.6(os)14.4(is)]TJ -14.5223 -1.0528 TD [(tr)17.3(an)15.1(sm)16.9(em)17.7(br)19.6(an)15.1(e)-473.5(c)0(o)15.1(n)0(d)21.2(u)0(c)15.1(t)0(a)18.4(n)0(c)20.8(e)-479.2(re)19.2(gu)21.2(la)12.8(to)18.9(r)-474.7(t)0(o)-464.8(t)0(h)18.9(e)-473.5(ce)14.7(ll)-467.2(me)17.7(m-)]TJ 0 -1.0471 TD [(br)19.6(an)15.1(e.)-291.8(G)12.4(e)0(n)15.1(i)0(s)17.7(t)0(e)18.4(i)0(n)-294.1(c)0(a)20.4(n)-296.7(ac)14.7(t)-299.1(o)0(n)-291.7(t)0(h)18.9(e)0(s)19.6(e)-302.8(ch)20.8(an)15.1(ne)20.8(ls)-289.6(to)-294.1(in)18.9(cr)19.2(ea)14.7(se)-287.7(th)13.2(e)]TJ 25.1977 66.1583 TD [(op)15.5(en)-479.9(ti)22.2(me)-483.1(an)20.8(d)-490.2(s)0(u)20(p)0(p)15.5(l)13.9(em)12(en)20.8(t)-486.8(t)0(h)18.9(e)-490.6(ef)30.6(fe)13.5(ct)-476.6(ac)14.7(hi)18.9(ev)20.8(ed)-479.9(wi)14.9(th)-476.2(4-)]TJ 0 -1.0471 TD [(ph)15.5(en)15.1(yl)18.9(bu)21.2(ty)13.2(ra)19.2(te)18.4(.)-284.9(4)0(-)19.6(p)0(h)15.5(e)0(n)20.8(y)0(l)13.2(b)0(u)21.2(t)0(y)18.8(r)0(a)13.5(t)0(e)-271.8(i)0(s)-278.3(a)0(l)18.5(r)0(e)19.2(a)0(d)15.1(y)-285.3(in)-271.4(cl)12.8(i)13.9(n)0(i)13.2(c)0(a)20.4(l)-287.7(us)20(e)]TJ 0 -1.0528 TD 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-1.0471 TD [(gen)-8.4(istein)-497(or)-481.1(genistein)-10.3(-like)-494.3(drugs)-496(as)-492.5(a)-490.6(pharm)-9(acolog)-7.8(ical)]TJ 0 -1.0527 TD [(treat)-11(ment)-339(for)-335.5(cystic)-341.4(fibrosis)-10.7(.)]TJ /F28 1 Tf 7.97 0 0 7.97 380.523 659.112 Tm [(Acknowled)11.4(gements.)]TJ /F7 1 Tf 8.5144 0 TD [(The)-400.8(technical)-396.7(assistan)10.5(ce)-406.3(of)]TJ -9.5103 -1.131 TD [(A.)-333.7(Ahlande)11.9(r)30.4(,)-340.4(M.)-330.3(Ljungkvist)-324.3(and)-334.1(L.)-333.9(Ljung)-336(is)-333.7(grate-)]TJ 0 -1.1239 TD [(fully)-492.4(acknowledg)12.1(ed.)]TJ /F6 1 Tf 8.966 0 0 8.966 402.349 608.655 Tm [(Refer)11.6(ences)]TJ /F7 1 Tf -10.3759 -1.998 TD [(1.)-1766.5(Brown)-417.4(CR,)-409.7(Hong-Brown)-419.1(LQ,)-413.3(Biwersi)-422.1(J,)-408.3(V)98.4(erkman)-416.6(AS,)]TJ 2.5165 -1.1128 TD [(W)70.8(elch)-290.8(WJ.)-293.2(Chemical)-297.4(chaperones)-293.3(correct)-290.9(the)-297.8(mutant)-294.2(phe-)]TJ T* [(notype)-321.6(of)-322.4(the)]TJ /F2 1 Tf 5.7033 0 TD (D)Tj /F7 1 Tf 0.6639 0 TD 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