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C., Nature 379, 413 (1996).",{"doi":1560},"10.1038\u002F379413a0",{"id":22,"text":1562,"url":22,"identifiers":1563},"For a review see L. P. Kouwenhoven et al. Proceedings of the Advanced Study Institute on Mesoscopic Electron Transport Curaçao 25 June to 5 July 1996 (Series E Kluwer Dordrecht Netherlands in press). Also available on the World Wide Web at .",{},{"id":22,"text":1565,"url":22,"identifiers":1566},"D. G. Austing T. Honda S. Tarucha Semicond. Sci. Technol. 11 212 (1996).",{"doi":1567},"10.1088\u002F0268-1242\u002F11\u002F3\u002F018",{"id":22,"text":1569,"url":22,"identifiers":1570},"10.1103\u002FPhysRevLett.77.3613",{"doi":1569},{"id":22,"text":1572,"url":22,"identifiers":1573},"M. Alonso and E. J. Finn Quantum and Statistical Physics (Addison-Wesley Reading MA 1968).",{},{"id":22,"text":1575,"url":22,"identifiers":1576},"10.1103\u002FPhysRevLett.78.1544",{"doi":1575},{"id":22,"text":1578,"url":22,"identifiers":1579},"Figure 2 actually reproduces in large detail in four different samples implying that the structure in the density of states in the leads is not originating from a random impurity potential but probably from the lateral confinement potential of the pillar.",{},{"id":22,"text":1581,"url":22,"identifiers":1582},"The sign of V sd is such that electrons first tunnel through the thicker barrier. In this situation only the excited states above the ground-state electrochemical potential are observed. For equal tunnel barriers tunneling out of the dot from excited states below the ground-state electrochemical potential can also be measured; see (2). Note that for a thick enough entrance barrier we can assume relaxation to the ground state between tunneling out and tunneling into the dot of the next electron.",{},{"id":22,"text":1584,"url":22,"identifiers":1585},"See for example J. J. Palacios L. Martin-Moreno G. Chiappe E. Louis C. Tejedor Phys. Rev. B 50 5760 (1994); for more references see the review by",{"doi":1586},"10.1103\u002FPhysRevB.50.5760",{"id":22,"text":1588,"url":22,"identifiers":1589},"Johnson N. F., J. Phys. Condens. Matter 7, 965 (1995) .",{"doi":1590},"10.1088\u002F0953-8984\u002F7\u002F6\u002F005",{"id":22,"text":1592,"url":22,"identifiers":1593},"Fock V., Z. Phys. 47, 446 (1928);",{"doi":1594},"10.1007\u002FBF01390750",{"id":22,"text":1596,"url":22,"identifiers":1597},"; C. G. Darwin Proc. Cambridge Philos. Soc. 27 86 (1930).",{"doi":1598},"10.1017\u002FS0305004100009373",{"id":22,"text":1600,"url":22,"identifiers":1601},"We believe that the smaller slopes in the experimental data of Fig. 5 for B > ∼7 T are due to a changing confinement potential because screening from the leads is modified by the formation of Landau levels in the leads. This is also reflected in the changing stripe width at high B.",{},{"id":22,"text":1603,"url":22,"identifiers":1604},"Thurner G., Herold H., Ruder H., Schlicht G., Wunner G., Phys. Lett. 89A, 133 (1982).",{"doi":1605},"10.1016\u002F0375-9601(82)90875-1",{"id":22,"text":1607,"url":22,"identifiers":1608},"Wagner M., Merkt U., Chaplik A. V., Phys. Rev. B 45, 1951 (1992).",{"doi":1609},"10.1103\u002FPhysRevB.45.1951",{"id":22,"text":1611,"url":22,"identifiers":1612},"Su B., Goldman V. J., Cunningham J. E., ibid. 46, 7644 (1992);",{},{"id":22,"text":1614,"url":22,"identifiers":1615},"Ashoori R. C., et al., Phys. Rev. Lett. 71, 613 (1993);",{"doi":1616},"10.1103\u002FPhysRevLett.71.613",{"id":22,"text":1618,"url":22,"identifiers":1619},"Schmidt T., et al., Phys. Rev. B 51, 5570 (1995).",{"doi":1620},"10.1103\u002FPhysRevB.51.5570",{"id":22,"text":1622,"url":22,"identifiers":1623},"For details of the calculation see",{},{"id":22,"text":1625,"url":22,"identifiers":1626},"Eto M., Jpn. J. Appl. Phys. 36, 3924 (1997);",{"doi":1627},"10.1143\u002FJJAP.36.3924",{"id":22,"text":1629,"url":22,"identifiers":1630},". In the numerically exact calculations every electron is assumed to occupy one of the lowest 15 single-particle states at B = 0. The strength of the Coulomb interaction is fixed such that e 2 \u002F ε ℏ︀\u002Fm*ωo = ℏ︀ω o (ε is the permittivity). (Interactions between electrons in the dot and in the leads are neglected.) The calculated results indicate that the many-body states consist of one main configuration [two main configurations for N = 3 and ( S M ) = (½ 2)] and several small contributions from other configurations. The depicted configurations in Fig. 3 overlap by ∼70% or more with the many-body ground states (the spin-polarized states overlap by more than 95%).",{},{"id":22,"text":1632,"url":22,"identifiers":1633},"For a theoretical analyses of the N = 2 excitation spectrum see for example",{},{"id":22,"text":1635,"url":22,"identifiers":1636},"Pfannkuche D., Gerhardts R. R., Maksym P. A., Gudmundsson V., Physica B 189, 6 (1993).",{"doi":1637},"10.1016\u002F0921-4526(93)90141-R",{"id":22,"text":1639,"url":22,"identifiers":1640},"Also for N ∼ 100 quantum dots the excitation spectra of N and N + 1 can be strongly correlated as observed recently by D. R. Stewart et al. [",{},{"id":22,"text":1642,"url":22,"identifiers":1643},"10.1126\u002Fscience.278.5344.1784",{"doi":1642},{"id":22,"text":1645,"url":22,"identifiers":1646},"We thank R. J. van der Hage J. Janssen Y. Kervennic J. E. Mooij S. K. Nair L. L. Sohn Y. Tokura and T. Uesugi for help and discussions. Supported by the Dutch Foundation for Fundamental Research on Matter. L.P.K. was supported by the Royal Netherlands Academy of Arts and Sciences.",{},{"id":1648,"createTime":1649,"updateTime":1649,"relativeEntities":1650,"slug":1651,"properties":1652,"entityType":378,"verifyStatus":379,"verifyTime":1649,"verifyNote":380,"syncStatus":21,"languages":1668,"translateLanguages":22,"viewCount":23,"primaryUrl":1669,"fullTextUrl":22,"authors":1670,"publicationType":420,"publisherRelationship":2141,"citationCount":2178,"citationInfo":2179,"publishDate":2183,"publishYear":2184,"citationAnalyzeStatus":21,"lastCitationAnalyze":22,"indexDatabases":22,"openAccess":22,"references":2185,"isForceReanalyzing":563},"4a3e2460-df7c-4e8c-a89b-245da2bab273","2024-09-11T23:58:44.403+00:00",[],"Phosphorylation-by-p38-MAPK-as-an-Alternative-Pathway-for-GSK3%CE%B2-Inactivation",{"mag":1653,"keywords":1655,"pmc":1656,"openalex":1658,"abstract":1660,"title":1662,"pm":1664,"doi":1666},{"VOID":1654},"2056907950",{},{"VOID":1657},"2597039",{"VOID":1659},"W2056907950",{"EN":1661},"\u003Cjats:p>Glycogen synthase kinase 3β (GSK3β) is involved in metabolism, neurodegeneration, and cancer. Inhibition of GSK3β activity is the primary mechanism that regulates this widely expressed active kinase. Although the protein kinase Akt inhibits GSK3β by phosphorylation at the N terminus, preventing Akt-mediated phosphorylation does not affect the cell-survival pathway activated through the GSK3β substrate β-catenin. Here, we show that p38 mitogen-activated protein kinase (MAPK) also inactivates GSK3β by direct phosphorylation at its C terminus, and this inactivation can lead to an accumulation of β-catenin. p38 MAPK–mediated phosphorylation of GSK3β occurs primarily in the brain and thymocytes. 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Genetic Vertigo\u003C\u002Fjats:title>\n          \u003Cjats:p>\n            Peoples living in high altitudes have adapted to their situation (see the Perspective by\n            \u003Cjats:bold>\n              \u003Cjats:related-article xmlns:xlink=\"http:\u002F\u002Fwww.w3.org\u002F1999\u002Fxlink\" ext-link-type=\"doi\" issue=\"5987\" page=\"40\" related-article-type=\"in-this-issue\" vol=\"329\" xlink:href=\"10.1126\u002Fscience.1192481\">Storz\u003C\u002Fjats:related-article>\n            \u003C\u002Fjats:bold>\n            ). To identify gene regions that might have contributed to high-altitude adaptation in Tibetans,\n            \u003Cjats:bold>\n              Simonson\n              \u003Cjats:italic>et al.\u003C\u002Fjats:italic>\n            \u003C\u002Fjats:bold>\n            (p.\n            \u003Cjats:related-article xmlns:xlink=\"http:\u002F\u002Fwww.w3.org\u002F1999\u002Fxlink\" ext-link-type=\"doi\" page=\"72\" related-article-type=\"in-this-issue\" vol=\"329\" xlink:href=\"10.1126\u002Fscience.1189406\">72\u003C\u002Fjats:related-article>\n            , published online 13 May) conducted a genome scan of nucleotide polymorphism comparing Tibetans, Han Chinese, and Japanese, while\n            \u003Cjats:bold>\n              Yi\n              \u003Cjats:italic>et al.\u003C\u002Fjats:italic>\n            \u003C\u002Fjats:bold>\n            (p.\n            \u003Cjats:related-article xmlns:xlink=\"http:\u002F\u002Fwww.w3.org\u002F1999\u002Fxlink\" ext-link-type=\"doi\" page=\"75\" related-article-type=\"in-this-issue\" vol=\"329\" xlink:href=\"10.1126\u002Fscience.1190371\">75\u003C\u002Fjats:related-article>\n            ) performed comparable analyses on the coding regions of all genes—their exomes. Both studies converged on a gene,\n            \u003Cjats:italic>endothelial Per-Arnt-Sim domain protein 1\u003C\u002Fjats:italic>\n            (also known as\n            \u003Cjats:italic>hypoxia-inducible factor 2\u003C\u002Fjats:italic>\n            α), which has been linked to the regulation of red blood cell production. Other genes identified that were potentially under selection included adult and fetal hemoglobin and two functional candidate loci that were correlated with low hemoglobin concentration in Tibetans. Future detailed functional studies will now be required to examine the mechanistic underpinnings of physiological adaptation to high altitudes.\n          \u003C\u002Fjats:p>",{"EN":2782},"Genetic Evidence for High-Altitude Adaptation in Tibet",{"VOID":2784},"20466884",{"VOID":2786},"10.1126\u002Fscience.1189406",[382],"https:\u002F\u002Fwww.science.org\u002Fdoi\u002F10.1126\u002Fscience.1189406",[2790,2809,2842,2859,2876,2893,2908,2923,2938,2953,2970,2985],{"id":2791,"sortIndex":120,"researcher":22,"roles":2792,"affiliations":2793,"properties":2804},"a8dd82c2-986d-43ac-8482-1a3298ce800b",[],[2794],{"id":2795,"sortIndex":23,"affiliation":2796,"properties":22},"c91210c9-b5e5-4267-89c5-bd8fef3c8243",{"id":2797,"createTime":2798,"updateTime":2798,"relativeEntities":2799,"slug":2800,"properties":2801,"entityType":49,"verifyStatus":21,"verifyTime":22,"verifyNote":22,"syncStatus":21,"languages":22,"translateLanguages":22,"viewCount":23},"fe1b9dec-5880-4fe1-ae95-5a3bb5137247","2024-12-23T23:58:04.032+00:00",[],"Research-Center-for-High-Altitude-Medicine-Qinghai-University-Medical-School-Xining-Qinghai-810001-People-s-Republic-of-China-",{"title":2802},{"EN":2803},"Research Center for High-Altitude Medicine, Qinghai University Medical School, Xining, Qinghai 810001, People's Republic of China.",{"openalex":2805,"title":2807},{"VOID":2806},"A5022391237",{"EN":2808},"Yingzhong Yang",{"id":2810,"sortIndex":128,"researcher":22,"roles":2811,"affiliations":2812,"properties":2835},"af56322c-bea1-45e0-88a6-4abfd4641de5",[],[2813,2824],{"id":2814,"sortIndex":120,"affiliation":2815,"properties":22},"66f8a135-1f42-46cc-a0e8-67f2a9f72ede",{"id":2816,"createTime":2817,"updateTime":2818,"relativeEntities":2819,"slug":2820,"properties":2821,"entityType":49,"verifyStatus":21,"verifyTime":22,"verifyNote":22,"syncStatus":21,"languages":22,"translateLanguages":22,"viewCount":23},"56fc5cda-7c33-435a-ba01-de5fdac98667","2023-12-12T23:48:55.457+00:00","2024-12-23T23:58:04.021+00:00",[],"Eccles-Institute-of-Human-Genetics-University-of-Utah-School-of-Medicine-Salt-Lake-City-UT-84112-USA",{"title":2822},{"VI":2823},"Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA",{"id":2825,"sortIndex":23,"affiliation":2826,"properties":22},"69184e5c-deed-45b4-9ed4-5401e96610aa",{"id":2827,"createTime":2828,"updateTime":2829,"relativeEntities":2830,"slug":2831,"properties":2832,"entityType":49,"verifyStatus":21,"verifyTime":22,"verifyNote":22,"syncStatus":21,"languages":22,"translateLanguages":22,"viewCount":23},"0629e730-6083-4744-8458-5539bf579fac","2024-12-23T23:58:04.007+00:00","2025-06-11T19:16:03.995+00:00",[],"Division-of-Hematology-and-Department-of-Pathology-ARUP-University-of-Utah-School-of-Medicine-and-VAH-Salt-Lake-City-UT-84112-USA-",{"title":2833},{"EN":2834},"Division of Hematology and Department of Pathology (ARUP), University of Utah School of Medicine and VAH, Salt Lake City, UT 84112, USA.",{"openalex":2836,"orcid":2838,"title":2840},{"VOID":2837},"A5042381475",{"VOID":2839},"https:\u002F\u002Forcid.org\u002F0000-0002-8019-2940",{"EN":2841},"Josef T. 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REGULATE ION-CHANNEL FUNCTION IN CAENORHABDITIS-ELEGANS MOTORNEURONS, GENETICS 139, 1261 (1995).",{"doi":3374},"10.1093\u002Fgenetics\u002F139.3.1261",{"id":22,"text":3376,"url":22,"identifiers":3377},"SIBLEY M.H., MUTATIONS IN THE ALPHA-2(IV) BASEMENT-MEMBRANE COLLAGEN GENE OF CAENORHABDITIS-ELEGANS PRODUCE PHENOTYPES OF DIFFERING SEVERITIES, EMBO JOURNAL 13, 3278 (1994).",{"doi":3378},"10.1002\u002Fj.1460-2075.1994.tb06629.x",{"id":22,"text":3380,"url":22,"identifiers":3381},"SIBLEY M.H., GENETIC IDENTIFICATION, SEQUENCE, AND ALTERNATIVE SPLICING OF THE CAENORHABDITIS-ELEGANS ALPHA-2(IV) COLLAGEN GENE, JOURNAL OF CELL BIOLOGY 123, 255 (1993).",{"doi":3382},"10.1083\u002Fjcb.123.1.255",{"id":22,"text":3384,"url":22,"identifiers":3385},"SNYDER P.M., MECHANISM BY WHICH LIDDLES SYNDROME MUTATIONS INCREASE ACTIVITY OF A HUMAN EPITHELIAL NA+ CHANNEL, CELL 83, 969 (1995).",{"doi":3386},"10.1016\u002F0092-8674(95)90212-0",{"id":22,"text":3388,"url":22,"identifiers":3389},"TSILIBARY E.C., 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NUCLEOTIDE-SEQUENCE FROM CHROMOSOME-III OF C-ELEGANS, NATURE 368, 32 (1994).",{"doi":3408},"10.1038\u002F368032a0",{"id":3410,"createTime":3411,"updateTime":3411,"relativeEntities":3412,"slug":3413,"properties":3414,"entityType":378,"verifyStatus":379,"verifyTime":3411,"verifyNote":380,"syncStatus":21,"languages":3428,"translateLanguages":22,"viewCount":23,"primaryUrl":3429,"fullTextUrl":22,"authors":3430,"publicationType":420,"publisherRelationship":3591,"citationCount":3628,"citationInfo":3629,"publishDate":3641,"publishYear":1175,"citationAnalyzeStatus":21,"lastCitationAnalyze":22,"indexDatabases":22,"openAccess":22,"references":3642,"isForceReanalyzing":563},"05c223a5-cfb4-4939-88ec-c841838a6389","2024-09-04T23:57:53.915+00:00",[],"Impaired-Nociception-and-Pain-Sensation-in-Mice-Lacking-the-Capsaicin-Receptor",{"mag":3415,"keywords":3417,"openalex":3418,"abstract":3420,"title":3422,"pm":3424,"doi":3426},{"VOID":3416},"2050781058",{},{"VOID":3419},"W2050781058",{"EN":3421},"\u003Cjats:p>\n            The capsaicin (vanilloid) receptor VR1 is a cation channel expressed by primary sensory neurons of the “pain” pathway. Heterologously expressed VR1 can be activated by vanilloid compounds, protons, or heat (&gt;43°C), but whether this channel contributes to chemical or thermal sensitivity in vivo is not known. Here, we demonstrate that sensory neurons from mice lacking VR1 are severely deficient in their responses to each of these noxious stimuli. VR1\n            \u003Cjats:sup>−\u002F−\u003C\u002Fjats:sup>\n            mice showed normal responses to noxious mechanical stimuli but exhibited no vanilloid-evoked pain behavior, were impaired in the detection of painful heat, and showed little thermal hypersensitivity in the setting of inflammation. Thus, VR1 is essential for selective modalities of pain sensation and for tissue injury–induced thermal hyperalgesia.\n          \u003C\u002Fjats:p>",{"EN":3423},"Impaired Nociception and Pain Sensation in Mice Lacking the Capsaicin Receptor",{"VOID":3425},"10764638",{"VOID":3427},"10.1126\u002Fscience.288.5464.306",[382],"https:\u002F\u002Fwww.science.org\u002Fdoi\u002F10.1126\u002Fscience.288.5464.306",[3431,3452,3473,3490,3507,3529,3544,3559,3574],{"id":3432,"sortIndex":126,"researcher":22,"roles":3433,"affiliations":3434,"properties":3445},"fd740ed6-88f1-4a5b-aa7d-de55e74367e3",[],[3435],{"id":3436,"sortIndex":23,"affiliation":3437,"properties":22},"41471b35-7685-4dca-aae8-479ad6bbcc7c",{"id":3438,"createTime":3439,"updateTime":3439,"relativeEntities":3440,"slug":3441,"properties":3442,"entityType":49,"verifyStatus":21,"verifyTime":22,"verifyNote":22,"syncStatus":21,"languages":22,"translateLanguages":22,"viewCount":23},"6f6762bc-aae5-449e-a3b9-a2091e6ed2e3","2024-09-04T23:57:53.991+00:00",[],"Departments-of-Anatomy-and-Physiology-and-the-W-M-Keck-Center-for-Neuroscience-University-of-California-San-Francisco-San-Francisco-CA-94143-0450-USA-",{"title":3443},{"EN":3444},"Departments of Anatomy and Physiology and the W. M. Keck Center for Neuroscience, University of California, San Francisco, San Francisco, CA 94143–0450, USA.",{"openalex":3446,"orcid":3448,"title":3450},{"VOID":3447},"A5007740596",{"VOID":3449},"https:\u002F\u002Forcid.org\u002F0000-0002-1710-6333",{"EN":3451},"Allan I. 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L. Fields Pain (McGraw-Hill New York 1987).",{},{"id":22,"text":3647,"url":22,"identifiers":3648},"Holzer P., Pharmacol. Rev. 43, 143 (1991).",{},{"id":22,"text":3650,"url":22,"identifiers":3651},"Szolcsanyi J., Jancso-Gabor A., Drug Res. 25, 1877 (1975).",{},{"id":22,"text":3653,"url":22,"identifiers":3654},"10.1016\u002F0006-8993(90)90498-Z",{"doi":3653},{"id":22,"text":3656,"url":22,"identifiers":3657},"M. J. Caterina et al. Nature 389 816 (1997).",{"doi":3658},"10.1038\u002F39807",{"id":22,"text":3660,"url":22,"identifiers":3661},"R. J. A. Helliwell et al. Neurosci Lett. 250 177 (1998).",{"doi":3662},"10.1016\u002FS0304-3940(98)00475-3",{"id":22,"text":3664,"url":22,"identifiers":3665},"M. Tominaga et al. Neuron 21 1 (1998).",{"doi":3666},"10.1016\u002FS0896-6273(00)80564-4",{"id":22,"text":3668,"url":22,"identifiers":3669},"R. Dubner D. D. Price R. E. Beitel J. W. Hu in Pain in the Trigeminal Region D. J. Anderson and B. Matthews Eds. (Elsevier Amsterdam 1977) pp. 57–66.",{},{"id":22,"text":3671,"url":22,"identifiers":3672},"10.1523\u002FJNEUROSCI.12-01-00086.1992",{"doi":3671},{"id":22,"text":3674,"url":22,"identifiers":3675},"S. N. Raja R. A. Meyer M. Ringkamp J. N. Campbell in Textbook of Pain P. D. Wall and R. Melzack Eds. (Churchill Livingstone Edinburgh 1999) pp. 11–55.",{},{"id":22,"text":3677,"url":22,"identifiers":3678},"10.1046\u002Fj.1460-9568.1998.00037.x",{"doi":3677},{"id":22,"text":3680,"url":22,"identifiers":3681},"10.1016\u002F0306-4522(95)00055-N",{"doi":3680},{"id":22,"text":3683,"url":22,"identifiers":3684},"10.1016\u002F0306-4522(96)00259-X",{"doi":3683},{"id":22,"text":3686,"url":22,"identifiers":3687},"Szallasi A., Blumberg P. M., Pharmacol Rev. 51, 159 (1999).",{},{"id":22,"text":3689,"url":22,"identifiers":3690},"10.1016\u002F0166-2236(94)90149-X",{"doi":3689},{"id":22,"text":3692,"url":22,"identifiers":3693},"10.1016\u002FS0165-6147(99)01294-8",{"doi":3692},{"id":22,"text":3695,"url":22,"identifiers":3696},"10.1038\u002F386173a0",{"doi":3695},{"id":22,"text":3698,"url":22,"identifiers":3699},"10.1074\u002Fjbc.272.34.20975",{"doi":3698},{"id":22,"text":3701,"url":22,"identifiers":3702},"10.1073\u002Fpnas.95.17.10240",{"doi":3701},{"id":22,"text":3704,"url":22,"identifiers":3705},"10.1073\u002Fpnas.93.26.15435",{"doi":3704},{"id":22,"text":3707,"url":22,"identifiers":3708},"10.1073\u002Fpnas.94.13.7006",{"doi":3707},{"id":22,"text":3710,"url":22,"identifiers":3711},"10.1152\u002Fjn.1999.82.6.2853",{"doi":3710},{"id":22,"text":3713,"url":22,"identifiers":3714},"10.1146\u002Fannurev.physiol.61.1.835",{"doi":3713},{"id":22,"text":3716,"url":22,"identifiers":3717},"10.1016\u002FS0306-4522(98)00535-1",{"doi":3716},{"id":22,"text":3719,"url":22,"identifiers":3720},"10.1523\u002FJNEUROSCI.19-24-10647.1999",{"doi":3719},{"id":22,"text":3722,"url":22,"identifiers":3723},"The VR1 gene was disrupted in JM1 mouse embryonic stem cells [",{},{"id":22,"text":3725,"url":22,"identifiers":3726},"10.1101\u002Fgad.9.20.2523",{"doi":3725},{"id":22,"text":3728,"url":22,"identifiers":3729},"]. See (58) for details of VR1-null mouse generation and northern blot analysis. All animal experiments were subject to institutional review and conducted in accordance with institutional guidelines.",{},{"id":22,"text":3731,"url":22,"identifiers":3732},"The 100-kb VR1 genomic bacterial artificial chromosome clone was used as a fluorescence in situ hybridization probe on metaphase 129SV\u002FJ fibroblasts and mapped by comparison with centromere and telomere positions (Genome Systems St. Louis MO).",{},{"id":22,"text":3734,"url":22,"identifiers":3735},"Immunohistochemistry was performed as described (7 38) with modifications. See (58) for details on immunohistochemistry and statistical analyses.",{},{"id":22,"text":3737,"url":22,"identifiers":3738},"10.1038\u002F18906",{"doi":3737},{"id":22,"text":3740,"url":22,"identifiers":3741},"Calcium imaging studies were performed on cultured dorsal root ganglion neurons as described (5 29) with modifications. See (58) for details.",{},{"id":22,"text":3743,"url":22,"identifiers":3744},"M. J. Caterina et al. data not shown.",{},{"id":22,"text":3746,"url":22,"identifiers":3747},"See (58) for details on patch-clamp analysis of cultured sensory neurons.",{},{"id":22,"text":3749,"url":22,"identifiers":3750},"Single cutaneous primary afferent neurons were recorded as described (54) [",{},{"id":22,"text":3752,"url":22,"identifiers":3753},"10.1152\u002Fjn.1992.68.2.581",{"doi":3752},{"id":22,"text":3755,"url":22,"identifiers":3756},"]. See (58) for details.",{},{"id":22,"text":3758,"url":22,"identifiers":3759},"Nociceptor conduction velocities were as follows. C fibers: VR1 +\u002F+ 0.56 ± 0.02; VR1 −\u002F− 0.58 ± 0.03; Aδ fibers: VR1 +\u002F+ 5.2 ± 1.5; VR1 −\u002F− 6.4 ± 1.2 m\u002Fs.",{},{"id":22,"text":3761,"url":22,"identifiers":3762},"Behavioral assays were performed as described (40 59) with modifications. See (58) for details.",{},{"id":22,"text":3764,"url":22,"identifiers":3765},"Some residual paw swelling was observed with high doses (>1 μg) of capsaicin. This could in principle indicate the existence of a resiniferatoxin-insensitive low-affinity capsaicin receptor but more likely reflects receptor-independent membrane perturbation effects similar to those previously reported with high-dose capsaicin [",{},{"id":22,"text":3767,"url":22,"identifiers":3768},"10.1097\u002F00001756-199511000-00009",{"doi":3767},{"id":22,"text":3770,"url":22,"identifiers":3771},"]. Indeed no significant swelling was seen with similarly effective concentrations of resiniferatoxin.",{},{"id":22,"text":3773,"url":22,"identifiers":3774},"Individually housed adult mice fed ad libitum were fluid-restricted to a 3-hour test period per day. Fluid intake was monitored by weighing sipper bottles (Nalgene Rochester NY) containing the indicated solutions before and after the test period.",{},{"id":22,"text":3776,"url":22,"identifiers":3777},"10.1126\u002Fscience.278.5336.279",{"doi":3776},{"id":22,"text":3779,"url":22,"identifiers":3780},"Body temperature and locomotor activity were continuously monitored with intraperitoneal telemetric probes and VitaView Software (MiniMitter Sun River OR). One week after probe implantation animals were injected subcutaneously on the back with capsaicin (1 mg\u002Fkg in 0.5 ml of 10% ethanol) or 10% ethanol alone.",{},{"id":22,"text":3782,"url":22,"identifiers":3783},"10.1113\u002Fjphysiol.1970.sp009027",{"doi":3782},{"id":22,"text":3785,"url":22,"identifiers":3786},"Median (and quartile range; qr) mechanical von Frey hair thresholds were as follows. C fibers: VR1 +\u002F+ 8.0 qr 12.0; VR1 −\u002F− 8.0 qr 8.0; Aδ fibers: VR1 +\u002F+ 5.6 qr 4.0; VR1 −\u002F− 8.0 qr 8.0 mN.",{},{"id":22,"text":3788,"url":22,"identifiers":3789},"See (58) for details on spinal cord recording.",{},{"id":22,"text":3791,"url":22,"identifiers":3792},"See (58) for details on analysis of heat-evoked spinal cord Fos immunoreactivity.",{},{"id":22,"text":3794,"url":22,"identifiers":3795},"10.1016\u002F0304-3959(88)90026-7",{"doi":3794},{"id":22,"text":3797,"url":22,"identifiers":3798},"H. O. Handwerker and P. W. Reeh in Proceedings of the VIth World Congress on Pain M. R. Bond J. E. Charlton C. J. Woolf Eds. (Elsevier Amsterdam 1991) pp. 59–70.",{},{"id":22,"text":3800,"url":22,"identifiers":3801},"10.1016\u002F0006-8993(94)90690-4",{"doi":3800},{"id":22,"text":3803,"url":22,"identifiers":3804},"J. Levine and Y. Taiwo in Textbook of Pain P. D. Wall and R. Melzack Eds. (Churchill Livingstone Edinburgh 1994) pp. 45–56.",{},{"id":22,"text":3806,"url":22,"identifiers":3807},"Mustard oil (10% in mineral oil) was painted on both hind paws and the hot plate assay was performed several minutes later.",{},{"id":22,"text":3809,"url":22,"identifiers":3810},"CFA and nerve injury experiments were performed as described (38 59) with modifications. See (58) for details.",{},{"id":22,"text":3812,"url":22,"identifiers":3813},"10.1161\u002F01.RES.84.8.921",{"doi":3812},{"id":22,"text":3815,"url":22,"identifiers":3816},"10.1016\u002FS0079-6123(08)62758-2",{"doi":3815},{"id":22,"text":3818,"url":22,"identifiers":3819},"10.1038\u002F22761",{"doi":3818},{"id":22,"text":3821,"url":22,"identifiers":3822},"W. J. Martin and A. I. Basbaum unpublished observation.",{},{"id":22,"text":3824,"url":22,"identifiers":3825},"10.1152\u002Fjn.1997.78.4.1841",{"doi":3824},{"id":22,"text":3827,"url":22,"identifiers":3828},"10.1002\u002Fcne.902610409",{"doi":3827},{"id":22,"text":3830,"url":22,"identifiers":3831},"10.1046\u002Fj.1460-9568.1999.00503.x",{"doi":3830},{"id":22,"text":3833,"url":22,"identifiers":3834},"10.1016\u002FS0304-3959(96)03176-4",{"doi":3833},{"id":22,"text":3836,"url":22,"identifiers":3837},"For supplemental data see www.sciencemag.org\u002Ffeature\u002Fdata\u002F1048712.shl.",{},{"id":22,"text":3839,"url":22,"identifiers":3840},"10.1038\u002F32897",{"doi":3839},{"id":22,"text":3842,"url":22,"identifiers":3843},"We thank members of the Dallman lab for experimental advice and assistance and J. Poblete L. Sun G. Gerkoff K. Schmidt N. Kileen and J. Meneses for expert technical advice and assistance. 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B. Ganset al., Geol. Soc. Am. Abstr. Programs31, 56 (1999).",{},{"id":22,"text":4294,"url":22,"identifiers":4295},"D. Lal, in Solar-Terrestrial Relationships and the Earth Environment in the Last Millenia, vol. 95 of Proceedings of the International School of Physics, Enrico Fermi (North Holland, Bologna, Italy, 1988), p. 216.",{},{"id":22,"text":4297,"url":22,"identifiers":4298},"J. Masarik, J. Beer, J. Geophys. Res.104, 12,099 (1999).",{},{"id":22,"text":4300,"url":22,"identifiers":4301},"10.1017\u002FS0033822200012297",{"doi":4300},{"id":22,"text":4303,"url":22,"identifiers":4304},"The same experiment was performed with the use of a zonally averaged global ocean circulation model with atmospheric and biospheric carbon exchange as described in ( 38 ). The more detailed model produced atmospheric Δ 14 C for the past 50 ka B.P. within ±10‰ of the simple box model. Subsequent glacial perturbation experiments were carried out in the box model as a computational expedient.",{},{"id":22,"text":4306,"url":22,"identifiers":4307},"Measurements of air bubbles in ice cores show that glacial atmospheric CO 2 concentration averaged ∼200 parts per million by volume (ppmv) compared to a preindustrial value of ∼280 ppmv ( 39 ). A reduction of terrestrial biomass to 65% of its preindustrial size is within the bounds of previous estimates ( 40 ) and is necessary to balance a lowering of glacial δ 13 C of oceanic ΣCO 2 by an average of –0.3‰ ( 41 ).",{},{"id":22,"text":4309,"url":22,"identifiers":4310},"Reduced deep-ocean ventilation is consistent with potentially restricted NADW formation and penetration in the glacial ocean. Global transects of radiocarbon distribution in the oceans suggest that NADW formation is responsible for sequestering up to 75% of the radiocarbon in the deep ocean ( 42 ).",{},{"id":22,"text":4312,"url":22,"identifiers":4313},"This change represents a 120-m lowering of sea level and the resultant shift of carbonate sedimentation off the continental shelves into deep water where dissolution is much more extensive. Discussion and details of the glacial carbon cycle boundary conditions are summarized in SOM Text fig. S3 and table S2.",{},{"id":22,"text":4315,"url":22,"identifiers":4316},"10.1029\u002F94PA00032",{"doi":4315},{"id":22,"text":4318,"url":22,"identifiers":4319},"J. F. McManus R. Francois J.-M. Gherardi L. D. Keigwin S. Brown-Leger in preparation.",{},{"id":22,"text":4321,"url":22,"identifiers":4322},"10.1029\u002FGM112p0059",{"doi":4321},{"id":22,"text":4324,"url":22,"identifiers":4325},"10.1017\u002FS0033822200018233",{"doi":4324},{"id":22,"text":4327,"url":22,"identifiers":4328},"10.1017\u002FS0033822200003672",{"doi":4327},{"id":22,"text":4330,"url":22,"identifiers":4331},"10.1016\u002FS0012-821X(00)00383-6",{"doi":4330},{"id":22,"text":4333,"url":22,"identifiers":4334},"10.1029\u002F1999GL010960",{"doi":4333},{"id":22,"text":4336,"url":22,"identifiers":4337},"K. D. Alverson R. S. Bradley T. F. Pederson Eds. Paleoclimate Global Change and the Future (Springer Verlag New York 2003).",{"doi":4338},"10.1007\u002F978-3-642-55828-3",{"id":22,"text":4340,"url":22,"identifiers":4341},"10.1029\u002FPA003i003p00317",{"doi":4340},{"id":22,"text":4343,"url":22,"identifiers":4344},"10.1126\u002Fscience.1083797",{"doi":4343},{"id":22,"text":4346,"url":22,"identifiers":4347},"This work was supported by NSF (OCE-0117356) Lawrence Livermore National Laboratory (LDRD-97-ERI-009) and the U.S. Department of Energy (W-7405-Eng-48). We thank the ODP Core Repository in Bremen for core sampling; B. Frantz and P. Zermeno for sample preparation assistance; C. Laj M. Frank J.-P. Valet and J. Stoner for providing their data of past geomagentic field intensities; and S. Johnsen for making available the revised GRIPss09sea chronology. This is WHOI contribution no. 11061.",{}]