CINXE.COM
Just a moment...
<!DOCTYPE html><html lang="en-US"><head><title>Just a moment...</title><meta http-equiv="Content-Type" content="text/html; charset=UTF-8"><meta http-equiv="X-UA-Compatible" content="IE=Edge"><meta name="robots" content="noindex,nofollow"><meta name="viewport" content="width=device-width,initial-scale=1"><style>*{box-sizing:border-box;margin:0;padding:0}html{line-height:1.15;-webkit-text-size-adjust:100%;color:#313131;font-family:system-ui,-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Helvetica Neue,Arial,Noto Sans,sans-serif,Apple Color Emoji,Segoe UI Emoji,Segoe UI Symbol,Noto Color Emoji}body{display:flex;flex-direction:column;height:100vh;min-height:100vh}.main-content{margin:8rem auto;max-width:60rem;padding-left:1.5rem}@media (width <= 720px){.main-content{margin-top:4rem}}.h2{font-size:1.5rem;font-weight:500;line-height:2.25rem}@media (width <= 720px){.h2{font-size:1.25rem;line-height:1.5rem}}#challenge-error-text{background-image:url(data:image/svg+xml;base64,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);background-repeat:no-repeat;background-size:contain;padding-left:34px}@media (prefers-color-scheme:dark){body{background-color:#222;color:#d9d9d9}}</style><meta http-equiv="refresh" content="390"></head><body class="no-js"><div class="main-wrapper" role="main"><div class="main-content"><noscript><div class="h2"><span id="challenge-error-text">Enable JavaScript and cookies to continue</span></div></noscript></div></div><script>(function(){window._cf_chl_opt={cvId: '3',cZone: "pnas.org",cType: 'managed',cRay: '91348f035bdafcf2',cH: 'MJMYX0hTmcLAigDDTv50Wwv3O_aDPEj2.VDujhdSFwk-1739782528-1.2.1.1-99pgpb.lAemQ12O.T7qjCM4eLuonYHGYCDlGo2_DDbzExwyiaDEuEPPaKsRGXa.5',cUPMDTk: "\/doi\/full\/10.1073\/pnas.96.15.8681?__cf_chl_tk=wU4kijJR5BD7GkR01Vqpo2rsRGoSUKV_C7cfGHLGPYg-1739782528-1.0.1.1-Py6uuhhhxoK5HeO5L4soG09eWeGLxWHkk7M11Ap33kE",cFPWv: 'b',cITimeS: '1739782528',cTTimeMs: '1000',cMTimeMs: '390000',cTplC: 0,cTplV: 5,cTplB: 'cf',cK: "",fa: "\/doi\/full\/10.1073\/pnas.96.15.8681?__cf_chl_f_tk=wU4kijJR5BD7GkR01Vqpo2rsRGoSUKV_C7cfGHLGPYg-1739782528-1.0.1.1-Py6uuhhhxoK5HeO5L4soG09eWeGLxWHkk7M11Ap33kE",md: "dueRoYCbnE2Pgzf3QJl766hKpheShBxKoMhXFMETruo-1739782528-1.2.1.1-Q6NyLicF2Qdd6XvNPfuTPX.njvOxaF2ALaDq9xgHxbYZlPht7cnZJalio5QlWbg8lwvJNM0B6ttv6BvsDacDKPhCIS75nxL_qvDjHOvDHn0hWzCycQVr79b3U86xbdLpLo2bDuFnEZDvU8yXdJNfXEUgCtvbyAiWzfo4jnxe_0urEbEcYNVU5dRSjry6TaOpHCJAqu0PVXHSHABDd0Twr76nbeV.AQHEfYCvAfNGbReC3IJf.qxzitDFDN7.MaQ7DLO_JfbBFy1SizUXyVLbii_6s53V6YM.sM4vu3dJUuqTWSRuc.nsVINO9msEo7Fd2jBMuBXzJuXm8AzF4DK7EQEd0XRXgo0BZmYyHS4mw.KXUnVJNyFJ7Ga97MyDbN7p2HD9TySWGcoaMaysKLYhlPgszom7s91R.l9AC5lSP3HUpKA93I8CSaqcicLfcpHpY5vdmXJTe2e7YKbYKcsM0xi1H3XDyiALNOFxIvBdl20fO2_RBcpTjnAyx0ZKTqevyIf04pikDogsuE6xokF_k8KkMEs6Jhn.WdjWHr_xdmm.e5GvUfwmvKn8cMa1QnC65Qx_LXkbl3.U3DYdxYqS_cGlM2neT3qr7Px8_wJdZKIP_Jlf5aSNXuc.9SrnAeHstIXAhX4yeaYo9QPKt41qTC2JN_Utyo4Wo_MIAId7pxJ6mco8Nxx_WDBtyfER.lCLnfdXyYC3LZUnZ_veonnq0wLFhKY0nCpbIOsu.TsHD4CEZomYT5odI08wV1A5BsrauxaDN0YBshWxU6CBlzE29S2FRU5zLK3YB1Cwc57B3t3i6KnWmLoprd90FhN4iw49769tircDn6rJfYEhHE.yU6FqIBCUrJc3qo_ChI3a9X_C2jkw3XETvQvfIkkXfh8OqBKJJj9pULVWPWV68i7DMU4opAsSujijLEbIpx9p2h0tLZOxkihwhL30HD1Nit7y9iltKO9g659oIarNikpvSsMJiBXpGZsE7PUeG7cX_COWZhaJBqZpmDPKI7QIw.L9M0TABF6u_44LLlJuS0vE3GMp2wSM8k4V.EmN8GThYlxglWzg.kPspSPVzsJkw7ojeEzlctAMaz6bsVZXYglSlu0hgqbtD60noOMHevsnzOutNrz1oyM9_ISw3lsQ9AutrJ6MdDe4bdaZg8.UrkM6LSSHuOkPDPRFF2DTjH_2BlIQO1yxQJO2zOWVuO1570vK8yVzO1JlcZrwe5RUUnQLbqaTHa6.1HxzuyC.9jgp3jhbGR.M54fh6m74HTHt90gA2nrEGALkThRhg9xhTnVtH59KwpT6BpBs6flHQ4LYHE6pORA0T0fC5fCxHtnwtWg7AJvteixP_LofbaJ9DjgwkaQ4CWYrmq24c0bnZU7QfOeOgVTnwOcqcyYcxuYMjNNnxDpsYe8le_Crxatie02.leDYzI05KjKsCyvsxScrr1CNNWaTM07tEDMD31Rgk2j5sg9dizJbGmyHddb2torVpnbpEbKf8nAWBJoyMOtH.LOkVey9lcW1tqOFvmjfN3FgEYyaoi2FPsimiMu4vqTvBTaA5tuOspXnnaaqPh4W3vvMRQkz6XhAn9Fblr68dhotkLidoDwpYbVziZmrdckDJw6H4gdD1faWxV68vzmrbylMDA5dfl0rqVyvh1cx7gotz1SccwObC0iaO.WQNIeoPdS2zd6cfg6l52Decldm2BtpZJd9TV674Dt3cCYjVsTnTT6GEAQ1XVVLln1pudz3S_zkx1EeHmeq5oewzTNmdam8V1wgOv7rCeUI9SYASoXsZRS4O3WXu5vXiMC8XyW.BBYF5.w8Vg1DoJNAwLsMXdNvWHX2WGfQBtCpsAtv59LUdmKQ.WLDl.FMUfTR95_F_h4x_WBzL.pHgRtH8ycLF9O7kCcKVz75iapdWDWy_cSSnjGhT3J.aO8svgJy__gdvRM9epnaYRvSgp57Is_yD9A7UErssjNkEKAKREKLQ_Bb.B01Fqef8B0UZZynbRwv0PDipSqANgz2NKQuN5_3CRrE_ZJK1Z70FyxHJONr2HWna02arPGYqUSWF2t9ADzF4jJvafhQcOIxVJFBmOEsXIYV0oXGPC2wsLxcZL6ejtRRjp_ZZnhd8LZN.166JUO_WxoynpNb.U3XqCgVTMA02ElXkG0pm6O_tq1QMv1P8aksjcGAVse2o9FASswgZ5fWfvTLv2m9YT.SYMaWeAwvubnj22cnUolPYCXSu7Yzfr8z.OG8TEYu5C4apU2RRgcQI1DtS15VcWeiZ6LoeOshu0PbNuJn391mWJyzmo56btfLb8mlT1622bQDbvlyEvdLKL29jDNO64lyOI6H95JhEurtwaizmEotLwO4pa8tWkzcpAYi6qrALH.z_6rrP74FuskBI414M.v8IkOxNHnnHQdjq6.jeO3pYj9xvXqsPMTWnHNShgKMMyof06HEapy5eW6FRf3tmQOJeqCs8TM_CVGZRY._yadFKHdGEKt883K2z3DgIIZlE08.rog9RMS4WofKBAeafiNSlFbONf_Tlb1tDSBaa0Ja6.CihxlXUF_dQJk.tiAsqjOskoQXV7eGGJrQqs8vjxaFw8QpMmhuq.g",mdrd: "7tXvFI03w23ziNuONbX3VWvJ0OQK1w.2wzSgzFtQDY4-1739782528-1.2.1.1-kRrnmssPA4_iiSacoNPTIsST0Ujr1mBm3ELj.sQwGuALXJr0JBQqdlOSIV5SlU4SFo0aUK71B4c.bbhTPAUtD2kHJLCdaHPPzh0BrdQ4m26g3rux6YIFizku018LuZoC.Frr0Sf9PWoUuy9EtdYqaXr8t7yiawJf98JWE5MD_.J.KMAHRnBBVNMNuAEv9PrZAo2xasGMbDoBV.lZP2noEdAUd3pKjAL3dWw3.mu3Yia5z3RMHPNlw3HOlbIPdtxjDour4ZYUsTxoUrEJMCj.ITD4N3hbjiTfHeg_snYF_Bwsi_hmNBWR9mEb9XQeDzl04zpuWb58XhgiN.ce8pq_wzi1Tpjs8nDq11ckJKZXzd4pqRcG5MPjkHhmlcNIWaPpCE3TmMDv_BPLOS20RbOhGiE623AuKvGfe6t8kMhOPAeKYEmY.DIxFZkfJPPOH9V8qsuaysFFIZO1Exzw6VUyp_nuXyHwDdRiJWT3dSuItqz_Yc.Z2wICLWrzU02Dw700_YF78QqsKyzRkCGNNUWn1V3nyeni_E3mnegO1DV_q7ajnSUAD1ek5knZLRX5WkaxHKNowYd4KbyB4JyqY74YsQ6JZLaTkGt2w_A7.G38pByxh31ey0FlyBMctcY6p04NTp7FW4GgjhB93S.1zDCvgw7P23ngViYZ9E82fQUvnydGw8ESU2Gi_nD6WGcDzaHsSTUK4toEHw35zWg4EeJ001bvfmL6iSOJZLmIMtjo4abXkpk57CociC1zmmE2bX6bUuQFRo3EMU3WfBmUQ5R0XZAWm090Is_gd4Z64UgcxHuPxWI1LaIgH96qwzxT2Rw7xWOD2aup6.rTQG0ygxo95kmcLraKjA7iOQwfBTbMQQnu6z0nJm_KKaCKkHUpqi79Tk181SkVRDlex2HttN82fOFvTHGepQy0SwtRYSTUmIBFan4x94RePD04fKJpP1NuqYXC7EId0svxC4se2emi4hQt7HlFSnqoW3WsQLt5oXKa8jtisIrKrHJduONJcAOKCvHVimztFEHMS5AHTdX0BTczp9nuWuYx_u3KEJ5pUuF8Gi5B846RnMZVfP4Llut9nuC4LfSRfQ_zFEnJmRd8CwM0UTSVxFI8EN2ftyYZEw7HrCnl1UkIEtAGQmvcEHgKMAxkldY7SO0_4QzaUdmCi1XF103AN3Fy5zwS26gbxdjTq9waWYE5UHlJbNiJTMDpZyAn00EuOF3MzTVSzko_FVz7xndIh5E525jAaTeXtEFpeVsZ6t00TdFjNLP9WjayLkGnztzei1pzNjH8U1uFNMEnbnps_myLmyov6YH9TXvODoFgEZ0bwwi2j1ELyrlu8k32TS_lrZK188To0y.xGYapKOOeUE1E5ohX0cuW.wqODk3_2_Y_c2MH4wxn2AijqGFahDVXUJlktmM6cI.qbuFx__L9jBmqUwCLJ8l5MaKDYcLl3qKjV1_orsS3gyI0GoNjsa_FR3fZUl3lOqq3OuyXKPIGAQi_QF9jbgUif7ysiV.w1TyKfDSc_NGyVwo4SELU1Y9cXYelbqNVVYZoOkjRbhOWEwz0tJDQwuY12jTu48darYTQdajZOxf78jV1qEMU_tVB7z3mKDmWDqglRPCasvwNlXXFYIpN1AEm6kqkYhShHrW2567vAK_pjRexFWjGN2iMdOkORZ.9G.zE5QBn7hxOCvt_ZOqKif8aDIBjTt1_WX2i7rFGePlP2YO0gqmAFUa2kx53nwxqoaXt27fJS0iSpo9Sa..VEz75.rFjCVmaYbw5nnpoPa8D3teaM7fYq_t7NWlyL6qYPigxaGVqkFl5NbbAZrmM9H68ti0slu0cmy_xaBOcPtA68.DphzgYD39DG.leU2f50ob.ZHVUwlC3fkKEMOfVN.u9t8neZMcVqJmxgNNgXdV.qjOJmr_Yv5xackqPm8xs9iAV2izoxrCU0tmUjs49XZrLSMg"};var cpo = document.createElement('script');cpo.src = '/cdn-cgi/challenge-platform/h/b/orchestrate/chl_page/v1?ray=91348f035bdafcf2';window._cf_chl_opt.cOgUHash = location.hash === '' && location.href.indexOf('#') !== -1 ? '#' : location.hash;window._cf_chl_opt.cOgUQuery = location.search === '' && location.href.slice(0, location.href.length - window._cf_chl_opt.cOgUHash.length).indexOf('?') !== -1 ? '?' : location.search;if (window.history && window.history.replaceState) {var ogU = location.pathname + window._cf_chl_opt.cOgUQuery + window._cf_chl_opt.cOgUHash;history.replaceState(null, null, "\/doi\/full\/10.1073\/pnas.96.15.8681?__cf_chl_rt_tk=wU4kijJR5BD7GkR01Vqpo2rsRGoSUKV_C7cfGHLGPYg-1739782528-1.0.1.1-Py6uuhhhxoK5HeO5L4soG09eWeGLxWHkk7M11Ap33kE" + window._cf_chl_opt.cOgUHash);cpo.onload = function() {history.replaceState(null, null, ogU);}}document.getElementsByTagName('head')[0].appendChild(cpo);}());</script></body></html>