CINXE.COM

<!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: "academic.oup.com",cType: 'interactive',cRay: '9203199dfffd91a8',cH: 'hWNDgPLkPQuHMKPeLmOShMTH7sDIBCAwfrF.Uoz87Rw-1741948272-1.2.1.1-IIzav3RidT0RZayaNxFaWt8DSaepvMsgWLLeCOmAsSocrxAUfCSP4OkQhQWnlBC4',cUPMDTk: "\/nar\/article-lookup\/doi\/10.1093\/nar\/gki057?__cf_chl_tk=hLOLt7eOD9Wfji_DXG5sa57PvEAiIps04mHlDK7huF4-1741948272-1.0.1.1-0dU_ohjv_FRDdE51a45hb3Vm.0.gW9c6kVOIqwz8AUs",cFPWv: 'g',cITimeS: '1741948272',cTTimeMs: '1000',cMTimeMs: '390000',cTplC: 0,cTplV: 5,cTplB: 'cf',cK: "",fa: "\/nar\/article-lookup\/doi\/10.1093\/nar\/gki057?__cf_chl_f_tk=hLOLt7eOD9Wfji_DXG5sa57PvEAiIps04mHlDK7huF4-1741948272-1.0.1.1-0dU_ohjv_FRDdE51a45hb3Vm.0.gW9c6kVOIqwz8AUs",md: "PrazoedMEK3yA67j8RcJkZHJ8cefExbzgivNhCj7h80-1741948272-1.2.1.1-dGUjfy1JQ1yBsiOt0m70ex8M7lBcbE6PTCeVxlNwfYUMAI8jSl4yZhjdLFktGeybnw4qmRaLHbJo4Yy7v2brqJMvA9S5txbeuDo8ddlUHKMbXQmKX6eAP.mcIDmyMElDaNyJ1fuxmrzBB.LxKQVFMRhvhlC4Jlc0qHi3GckPa0WfMjtWFPQgenmJ1RmUY8.RFw.gUSizoriA2RtoCBS.5WKfZpQdlQz5sB_x7s1AmVW.TbCQCvHaHxt59XINIAWQ3yVO0sNR_3XvNRb_SxGYrqscoTax.uxtjI2T0G3gpiUBQsXpYBT.jB0A.563nOp3D2h1Ok8lILm9AL3GeIptIbJpPVSMWvhJYBJPbh9Uox2EQK7gxK2vaDCm02j8HjiovOQR3qDkGAsrtxiT.7lkFENO.BKYV3FAQnfxLC_sXFX78HZtwwiyMZ.mvp_4PpGy4Lv_disOIDBgbZVVRdKW9q0v.1RSEsQBWEtpIqO6164963iJ7uSVzXFrc1IG8pgK4L0TyRPKprra4P_iKsaHqgEuemtQq7ucoxRNHLwQ2OU__dyG7lDSjBOxt3sbwiXGijKfXM2JyRq5GAVXek7ldWJyohWe1Wis41NeLlNIZwubTIjgRmcBbGitcMRFXhW7PbOr1IjyxqqWfg7Xkgq165oSM2KEw1msV7ZyJj6aLGbI6sazysvQwLQbZUsU2hg35m40ATm._ZvI_VJhxZUm7ZigsteL9gzr8sfD8KDyuOEmH4aS_XnOLNxmD7fk60l3RceSHNCxSNTVliO46xl5ce0PzEMs7oaiECTMQRAsPs7jYKLpI4n6ZCr50WrkznI462dDYbLxhr7__WAsWWZ9GXDk9dO0eZw1OlSHOqww2ye7r791RgXMVlvdmbetmbM8XwjvwvnncGZS7eS3mN6hwHtWolBDOGg14EhZqSJp8lNiXgI6_9WacI.PEkXoPyWvT8P9lBYwgUcKZoAyZa4r076apm34SndhID_OyCiI.R48uBx9zOUN9WAp2lf410l9phb8TFw6h8TLuhYl5NYovow1IcyNxwwtsVbHDkmO57UJMfMhlevMlQu_FCf8P5CiQL2I09hVWs1HjIYFLQRlPQis0IW7Xino66KlyxXh7fCbX00odlvaYP0q.zaAqOSzd1kWf2VNy4dsBhiHfRXK3.q2kg9N7PxM5Wl0Rowz3iEi2y2VgIpWcFmupiRj7Q0l3UiMBScFZerNkkZ1qEoBsySGwM1nnX2qK5qpw0pD.53Cb6zFpdJidU0BApLitQbk0kvIhJXnN1_p87PJSe8Shevj6DlIs9EZkyLpsD8XAcw",mdrd: "yhl29Vr28cuA6gA8TdTr2YrIIp3r1K_ov9GMkPSXjTY-1741948272-1.2.1.1-I0UsElqG63l79Irv7uDGKMyut2dUg0hdPvlm8CvxLtkUQpH4wD4eqxud8WTjLINK7Z3G2s_6eEvzrXtbJRSV1sloTabeonb7zyT5HZfKwYxEloGpa.2POHW6In_tVlPnzPpwPnMzTGZ24Hcs9wRmLzshgr8kqjxkRCbJIBW0BprNXUVgy8PMcEoMjPY1dvmOfKVpiCiT3PEHBh8GyG5KBnZFZukUmVvJ6vcToPdw_NaIQEknDl0laTnnHCA0Nb9xbyXD72T2JDD8jxccD6Hu5DlowH1rFA0NMMhtpYPUQAa8tByS6ssmtkZrDgU5UIi.4yjR02uMdmneo1r2htqEV5q5sBYF54d3B5.fxc2K_uUcQyb2PCHIeewKwjrKvloMzrwZ_oqFBS6cZY1AoEBNZ0hKV0TXnEPoP6.i9epuBJyxadf7hUwBAKctIDzrBLQypyWFMDgFtmI9Mf9FE4CkgFRr_B.W2OBWNaYuwbaqPA3k1AeyoI.wiGFIn6E90j2YPgje_nrVCRUBmO_4fuf8U4whCgh3HAXCj.ws2kbsVnr4t7sN7kANxtwOBDdNJ.5C8kDCA6dJACUvMrVV450xaA6VPTSDKqXoOd03CAZm3x1gscCAh7GkZqfSyrBrbxLqI5fwcUoYE4F5uis6MLtysF9zAY2r3ULhzw88NDEUFCRyZbIuPr65e8BygiAMCvwCHOzCENxQEf73M7oPqzB3GFb_ddoTz61PLISkvarDSTubbA3FU.z0bvZHUYudPVOexN0VUnNTQDLr2_3Tdz6YcLjJFHbXnk.hWrljGaV_xus5LWgi5CzFQ6SLxfbjHmgG4AA_9lvvkJEWYADhv4k6GolXCJxce8VAwbhBE9Rvcvr6YuIODfXgdlBlaWen5Ic1GvHwPR07d3PTqZ1fpfAylLoDaScNemqX5yyQ.olTaYqgtqVYLy83eFH4hJaNPPyp4uk32eVhq3KpAKmNpKFVcErgXDXMSf8DsBV0gQOdF7YVF5VVpSH0E3dADSIL8Bl_ItRC3_RNpb0VE53a8Pavjc8ZTgrwL.lvhOPj83ZEFWdKufinkrzWx9Rpsk2QtbkB8ZI8.4GGOCdrB_IDw1QqEt2dBr.robQopS5jutlaxxWCDrBaE2hu6awcHYOsHyyoX4YSRFKtwBY9TYSD7KjgQuUR6Ia.yEJaXPzdjLVz6AmiNmdUgTzFchTX0Ve6ptbL09PUpycqE1Vo967Shvt9Kar8D6eGp.1yDlNco44CLFLw8gKeQC_k9Qg7YytN5eHbllDk8.q_IW.qpJQ73.eXENSIwFOD9pq_SNA7SsyYhsTMkt6di.wjSndV.qeIj_wOlMv.iYOxtcZ6ds5.ddk.dkMPDairjwvxlc5upe_ygwjEmFyW5WjRzDwkjehf6LAVDxY4Q3Mheq60cKuwxbIFsMSey_3nHCyZWSDkEP_vVF.kmbRBMIERLt8U34SsqlBY_HkTchOJAaJpL551eeZmzkcQk_ee4j1yFGrHNu23MF8cbaOzlewJ.CiDf_KQ5p9ZoKG54ZB61w76uQYCgFalsvdUe3tnrj4yo9IPMYdFmVcx0QuhTMEsA29JlN4RJ0FKiXy4Jd5lsMsP.XxWZbuHm08fokwx2TQBkInMtceIw43vMVAfUr9z1vXhM_y81IG1fQEvRXkT83Lnfg8sunLEwYwofxOBzzoIuDBzhdZ_K78BGjHsykn1lObWE5ecjpuwz44HmBNKTM8MmHD083pZ2IY2LucxRqPHr51Tn5h73DfDEMKo1EeJsOyaF300PbvzbL1EYtwXLSw7Ry7rqJp_Az7SATHv4kLIhYoGIcuIuDfxgglxbyDT43QU6HOJimNAOo1mVKVvXJ.kNZR5lOZXLv_MDyUs1Q504srVXaYraG6B0Oo0T2ki63NHXbPPjF4kkxm9J.bSvAv_c5rS8qU47GEU0E8fmJpx.gHblc98nEl9LobOFPjig6u6KICzzUX6xsh0pPOhmrfFtJjbYqpfTj7n3_BZT7vDl.cGvRNBz_UvLECCYaJP31ZQnamMjcM8pe9MLkd8QRrD3JXKWE9vJA"};var cpo = document.createElement('script');cpo.src = '/cdn-cgi/challenge-platform/h/g/orchestrate/chl_page/v1?ray=9203199dfffd91a8';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, "\/nar\/article-lookup\/doi\/10.1093\/nar\/gki057?__cf_chl_rt_tk=hLOLt7eOD9Wfji_DXG5sa57PvEAiIps04mHlDK7huF4-1741948272-1.0.1.1-0dU_ohjv_FRDdE51a45hb3Vm.0.gW9c6kVOIqwz8AUs" + window._cf_chl_opt.cOgUHash);cpo.onload = function() {history.replaceState(null, null, ogU);}}document.getElementsByTagName('head')[0].appendChild(cpo);}());</script></body></html>