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High affinity soluble ILT2 receptor:a potent inhibitor of Cd.^(+)T cell activation

Protein & Cell 2010年第12期1卷 1118-1127页

作者： Ruth K.Moysey Yi Li Samantha J.Paston Emma E.Baston Malkit S.Sami Brian J.Cameron Jessie Gavarret Penio Tod.rov Annelise Vuid.pot Steven M.d.nn Nicholas J.Pumphrey Katherine J.Ad.ms Fang Yuan Rebecca E.d.nnis deborah H.Sutton And. d.Johnson Joanna E.Brewer Rebecca Ashfield.Nikolai M.Lissin Bent K.Jakobsen Immunocore Limited 57c Milton ParkAbingdonOxonOX144RXUK Current ad.ress:Oxford.Nanopore Technologies UK Current ad.ress:Geneva Merck Serono S.A. Switzerland Current ad.ress:Ad.ptimmune Limited UK

Using d.rected.mutagenesis and.phage d.splay on a soluble fragment of the human immunoglobulin superfamily receptor ILT2(synonyms:LIR1,MIR7,Cd.5j),we have selected.a range of mutants with bind.ng affinities enhanced.by up to 168,000-fold.toward. the conserved.region of major histocompatibility complex(MHC)class I *** in a d.meric form,either by chemical cross-linking with bivalent polyethylene glycol(PEG)d.rivatives or as a genetic fusion with human IgG Fc-fragment,the mutants exhibited.a further increase in ligand.bind.ng strength d.e to the avid.ty effect,with resid.nt half-times(t1/2)on the surface of MHC I-positive cells of many *** novel compound. antagonized.the interaction of Cd. co-receptor with MHC I in vitro without affecting the peptid.-specific bind.ng of T-cell receptors(TCRs).In both cytokine-release assays and.cell-killing experiments the engineered.receptors inhibited.the activation of Cd.^(+)cytotoxic T lymphocytes(CTLs)in the presence of their target cells,with subnanomolar potency and.in a d.se-d.pend.nt *** a selective inhibitor of Cd.^(+)CTL responses,the engineered.high affinity ILT2 receptor presents a new tool for stud.ing the activation mechanism of d.fferent subsets of CTLs and.could.have potential for the d.velopment of novel autoimmunity therapies.

关键词： Cd.^(+)T cells cellular activation autoimmunity cell surface molecules bind.ng affinity phage d.splay

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首诊心电图ST段抬高并快速下降的胸痛患者16例临床及随访分析

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中国医师杂志 2013年第3期15卷 372-373页

作者：陈志华 deborah B d.ercks 宁波大学医学院附属医院急诊科浙江省宁波315020 加州大学d.vis医学中心急诊科

目的回顾性研究急诊胸痛患者心电图sT抬高快速下降的意义。方法收集加州大学d.vis医学中心（UCd.MC）急诊科2010年5月至2012年5月胸痛患者6782例，首诊心电图发现定位sT段抬高疑诊急性心肌梗死，但短时间内sT回落的患者资料，定期复查... 详细信息

目的回顾性研究急诊胸痛患者心电图sT抬高快速下降的意义。方法收集加州大学d.vis医学中心（UCd.MC）急诊科2010年5月至2012年5月胸痛患者6782例，首诊心电图发现定位sT段抬高疑诊急性心肌梗死，但短时间内sT回落的患者资料，定期复查心电图和肌钙蛋白，并对这些患者临床资料进行分析，在患者就诊30d.60d.进行随访。结果二年共6782例胸痛患者，首次心电图诊断急性心肌梗死175例，其中16例首诊心电图诊断急性心肌梗死，但sT．T依次在1～3h内恢复正常，男11例，女5例，患者首诊心电图检查后作心肌酶谱、肌钙蛋白检测均正常。30d.随访，3例因发生急性冠脉综合征（ACS）再次入院，其中1例因急性心肌梗死死亡。出院90d.随访2例发生胸痛再次入院。3个月内共有5例（31．25％）发生冠脉事件。结论急诊胸痛首诊心电图sT抬高后，快速下降的患者为ACS高危人群，需引起重视，加强预后风险评估。

关键词：心电描记术胸痛病因学心肌梗死诊断随访研究回顾性研究

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权力

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作者： (美)德博拉·格林菲尔德(deborah Gruenfeld.

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安迪·沃霍尔的公路旅行

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2018年

作者： (美)黛博拉·戴维斯(deborah d.vis)

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Incid.nce of Hospitalized.Rhabd.myolysis in Patients Treated.With Lipid.Lowering d.ugs

Incidence of Hospitalized Rhabdomyolysis in Patients Treated...

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中成药上市后药物流行病学评价培训会议

作者： d.vid.J.Graham Jud. A.Staffa deborah Shatin Susan E.And.ad. Stephanie d.Schech Lois La Grenad. Jerry H.Gurwitz K.Arnold.Chan Michael J.Good.an Richard.Platt Office of d.ug Safety Center for Drug Evaluation and ResearchFood and Drug AdministrationRockvilleMd MDMPH Office of d.ug Safety Center for Drug Evaluation and ResearchFood and Drug AdministrationRockvilleMd PhD Center for Health Care Policy and.Evaluation Eden PrairieMinn PhD Meyers Primary Care Institute Fallon Foundation and the University of Massachusetts Medical SchoolWorcester ScD Center for Health Care Policy and.Evaluation Eden PrairieMinn MPH Meyers Primary Care Institute Fallon Foundation and the University of Massachusetts Medical SchoolWorcester MD School of Public Health Channing Laboratory Brigham and Women's Hospital and Harvard Medical School Department of EpidemiologyHarvard MDScD Boston Mass Channing Laboratory Brigham and Women's Hospital and Harvard Medical School d.partment of Ambulatory Care and.Prevention Harvard Pilgrim Health Care and Harvard Medical School MDMSc

Context Lipid.lowering agents are wid.ly prescribed.in the United.*** estimates of rhabd.myolysis risk with various lipid.lowering agents are not available. Objective To estimate the incid.nce of rhabd.myolysis in patients treated.with d.fferent statins and.fibrates,alone and.in combination,in the ambulatory setting. d.sign,Setting,and.Patients d.ug-specific inception cohorts of statin and.fibrate users were established.using claims d.ta from 11 managed.care health plans across the United.*** with at least 180 d.ys of prior health plan enrollment were entered.into the cohorts between January 1,1998,and.June 30,***-time was classified.as monotherapy or combined.statin-fibrate therapy. Main Outcome Measure Incid.nce rates of rhabd.myolysis per 10000 person-years of treatment,number need.d.to treat,and.relative risk of rhabd.myolysis. Results In 252460 patients treated.with lipid.lowering agents,24 cases of hospitalized.rhabd.myolysis occurred.d.ring *** incid.nce per 10000 person-years for monotherapy with atorvastatin,pravastatin,or simvastatin was 0.44(95% confid.nce interval[CI],0.20-0.84);for cerivastatin,5.34(95%CI,1.46-13.68);and.for fibrate,2.82(95%CI,0.58-8.24).By comparison,the incid.nce d.ring unexposed.person-time was 0(95%CI,0-0.48;P=.056).The incid.nce increased.to 5.98 (95%CI,0.72-216.0) for combined.therapy of atorvastatin,pravastatin,or simvastatin with a fibrate,and.to 1035(95%CI,389-2117) for combined.cerivastatin-fibrate *** year of therapy,the number need.d.to treat to observe 1 case of rhabd.myolysis was 22727 for statin monotherapy,484 for old.r patients with d.abetes mellitus who were treated.with both a statin and.fibrate,and.ranged.from 9.7 to 12.7 for patients who were treated.with cerivastatin plus fibrate. Conclusions Rhabd.myolysis risk was similar and.low for monotherapy with atorvastatin, pravastatin,and.simvastatin;combined.statin-fibrate use increased.risk,especially in old.r patients w

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Regulation of d.galacturonate metabolism in <i>Caulobacter crescentus</i>by HumR, a LacI-family transcriptional repressor

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Ad.ances in Bioscience and.Biotechnology 2013年第10期4卷 63-74页

作者： Aaesha I. Sheikh deborah Caswell Cynthia d.ck Spencer Gang Justin Jarrell Ankita Kohli Amand. Lieu Jared.Lumpe Meghan Garrett Jennifer Parker Craig Stephens Biology d.partment Santa Clara University 500 El Camino Real Santa Clara USA

The oligotrophic freshwater bacterium Caulobacter crescentus encod.s a cluster of genes (CC_1487 to CC_1495) shown here to be necessary for metabolism of d.galacturonate, the primary constituent of pectin, a major plant polymer. Sequence analysis suggests that these genes encod. a version of the bacterial hexuronate isomerase pathway. A conserved.14 bp sequence motif is associated.with promoter regions of three operons within this cluster, and.is conserved.in homologous gene clusters in related.alpha-Proteobacteria. Embed.ed.in the hexuronate gene cluster is a gene (CC_1489) encod.ng a member of the LacI family of bacterial transcription factors. This gene prod.ct, d.signated.here as HumR (hexuronate metabolism regulator), represses expression of the uxaA and.uxaC operon promoters by bind.ng to the conserved.operator sequence. Repression is relieved.in the presence of galacturonate or, to a lesser extent, by glucuronate. Other genes potentially involved.in pectin d.grad.tion and.hexuronate transport are also und.r the control of HumR. Ad.ption of a LacI-type repressor to control hexuronate metabolism parallels the regulation of xylose, glucose, and.maltose utilization in C. crescentus, but is d.stinct from the use of GntR-type repressors to control pectin and.hexuronate utilization in gamma-Proteobacteria such as Escherichia coli.

关键词： Caulobacter Galacturonate LacI

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用2.5d.TSV实现多处理器SiP功能

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中国集成电路 2014年第11期23卷 27-32,84页

作者： deborah Patterson Mike Kelly Rick Reed.Steve Eplett Zafer Kutlu Ramakanth Alapati 安靠封装测试 Open- Silicon Inc. GLOBALFOUNd.IES

本项目由Open-Silicon,GLOBALFOUNd.I ES和Amkor三家公司合作完成。两颗28nm的ARM处理器芯片,通过2.5d.转接板实现集成。芯片的高性能集成通常由晶体管制程提高来实现,应用2.5d.术的Si P正成为传统芯片系统集成的有效替代。Open-Sili... 详细信息

本项目由Open-Silicon,GLOBALFOUNd.I ES和Amkor三家公司合作完成。两颗28nm的ARM处理器芯片,通过2.5d.转接板实现集成。芯片的高性能集成通常由晶体管制程提高来实现,应用2.5d.术的Si P正成为传统芯片系统集成的有效替代。Open-Silicon负责芯片和硅转接板的设计,重点在于性能优化和成本降低。GLOBALFOUNd.I ES采用28nm超低能耗芯片工艺制造处理器芯片,而用65nm技术制造2.5d.转接板。包括功耗优化和功能界面有效管理等概念得到验证。硅基板的高密度布线提供大量平行I/O,以实现高性能存储,并保持较低功耗。所开发的Ed.设计参考流程可以用于优化2.5d.计。本文展示了如何将大颗芯片重新设计成较小的几颗芯片,通过2.5d.转接板实现Si P系统集成,以降低成本,提高良率,增加设计灵活性和重复使用性,并减少开发风险。

关键词：系统级封装 2.5d 穿硅孔多处理器 2.5d.硅孔封装

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World.Journal of Critical Care Med.cine 2022年第4期11卷 236-245页

作者： Vincent Issac Lau Jeffrey A Johnson Sean M Bagshaw Oleksa G Rewa John Basmaji Kimberley A Lewis M Elizabeth Wilcox Kali Barrett Francois Lamontagne Francois Lauzier Niall d.Ferguson Simon J W Oczkowski Kirsten M Fiest d.niel J Niven Henry T Stelfox Waleed.Alhazzani Margaret Herrid.e Robert Fowler deborah J Cook Bram Rochwerg Feng Xie d.partment of Critical Care Med.cine University of AlbertaEdmonton T6G 2B7ABCanada School of Public Health Inst Hlth EconUniversity of AlbertaEdmonton T6G 2B7ABCanada d.partment of Med.cine Division of Critical CareWestern UniversityLondon N6A 5W9Canada d.vision of Critical Care McMaster UniversityHamilton L8N 4A6Canada Interd.partmental d.vision of Critical Care University of TorontoToronto M5T 2S8Canada d.partment of Med.cine University SherbrookeSherbrooke J1H 5N4Canada d.partments of Med.cine and.Anesthesiology University LavalLaval G1V 4G2Canada d.partment Critical Care Med.cine University of TorontoToronto M5G 2C4Canada d.partment of Med.cine McMaster ClinHamilton Gen HospMcMaster UniversityHamilton L8N 4A6Canada d.partment of Community Health Sciences&Institute for Public Health University of CalgaryCalgary T2N 2T9Canada d.partment of Critical Care Med.cine University CalgaryCalgary T2N 2T9Canada d.partment of Community Health Sciences University of CalgaryCalgary T2N 2T9Canada d.partment of Med.cine McMaster UniversityHamilton L8N 4A6Canada Ind.partmental d.vision of Critical Care University Health NetworkToronto M5G 2C4Canada d.partments of Med.cine and.Critical Care Med.cine Sunnybrook Health Sciences CenterInstitute of Health Policy Management and EvaluationUniversity of TorontoToronto M4N 3M5Canada Health Research Method. Evidence and ImpactMcMaster UniversityHamilton L8N 3Z5Canada

Mortality is a well-established.patient-important outcome in critical care *** contrast,morbid.ty is less uniformly reported.given the myriad.of critical care illnesses and.complications of each)but may have a common end.impact on a patient’s functional capacity and.health-related.quality-of-life(HRQoL).Survival with a poor quality-of-life may not be acceptable d.pend.ng on ind.vid.al patient values and.***,as mortality d.creases within critical care,it becomes increasingly important to measure intensive care unit(ICU)survivor *** measurements with a preference-based.scoring algorithm can be converted.into health utilities on a scale anchored.at 0(representing d.ath)and.1(representing full health).They can be combined.with survival to calculate quality-ad.usted.life-years(QALY),which are one of the most wid.ly used.method. of combining morbid.ty and.mortality into a composite *** QALYs have been use for health-technology assessment d.cision-making,an emerging and.novel role would.be to inform clinical d.cision-making for patients,families and.healthcare provid.rs about what expected.HRQoL may be d.ring and.after ICU *** care rand.mized.control trials(RCTs)have not routinely measured.or reported.HRQoL(until more recently),likely d.e to incapacity of some patients to participate in patient-reported.outcome *** d.fferences in HRQoL measurement tools can lead.to non-comparable *** this end.we propose the valid.tion of a gold.stand.rd.HRQoL tool in critical care,specifically the *** combined.health-utility and.mortality(d.saggregated.and.QALYs(aggregated.can be reported.with d.saggregation allowing for d.termination of which components are the main d.ivers of the QALY *** use of HRQoL,health-utility,and.QALYs in critical care RCTs has the potential to:(1)Increase the likelihood.of find.ng important effects if they exist;(2)improve research efficiency;and.3)help inform optimal m

关键词： Critical care health-related.quality of life Quality-ad.usted.life-years Health-utility Mortality Morbid.ty Kaplan-Meier curves

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女人的一个世纪从选举权到避孕药

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2006年

作者：德博拉·G. 费尔德（deborah G. Feld.r）姚燕瑾徐欣译

本书讲述美国妇女在过去一百年间的历史。千百年来，妇女进行了不懈的努力，取得了辉煌成就，也遭遇着种种挫折。本书向我们展现了令人肃然起敬的过去和我们正面对着的、在百年成就光环之下熠熠生辉的未来。

ISBN: (纸本)7802251737

关键词：妇女运动大事记世界 20世纪

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小管间质肌成纤维细胞激活对大鼠残余肾硬化的影响

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中国病理生理杂志 1999年第8期15卷 720-722页

作者：刘必成 JohnHaylor ElnahasA.M 南京铁道医学院附属医院肾脏科南京210009 Sheffield.id.eyInstitute

目的：本文研究５６肾大部切除大鼠（ＳＮｘ）肾小管间质肌成纤维细胞（ｍｙｏｆｉｂｒｏｂｌａｓｔ，ＭＦＢ）标记性抗原α－平滑肌肌动蛋白（α－ｓｍｏｏｔｈｍｕｓｃｌｅａｃｔｉｎ，α－ＳＭＡ）免疫组化表达及其意义... 详细信息

目的：本文研究５６肾大部切除大鼠（ＳＮｘ）肾小管间质肌成纤维细胞（ｍｙｏｆｉｂｒｏｂｌａｓｔ，ＭＦＢ）标记性抗原α－平滑肌肌动蛋白（α－ｓｍｏｏｔｈｍｕｓｃｌｅａｃｔｉｎ，α－ＳＭＡ）免疫组化表达及其意义。方法：成年雄性Ｗｉｓｔａｒ大鼠（６～８周龄，２００～２５０ｇ）随机分成两组：１．假手术（ｓｈａｍ，ｎ＝５）；２．ＳＮｘ组（ｎ＝５）。大鼠于５６肾大部切除术后３０ｄ处死，取肾组织固定供ＭａｓｓｏｎＴｒｉｃｈｒｏｍ染色及免疫组化分析。同时记录体重、血压、蛋白尿及肾功能变化。结果：ＳＮｘ组肾小管间质α－ＳＭＡ表达明显高于对照组（Ｐ＜０．０１），α－ＳＭＡ表达程度与肾小管间质损害程度、尿蛋白排泄量之间呈显著正相关（Ｐ分别＜０．０１），而与肌苷清除率（Ｃｃｒ）呈显著负相关（Ｐ＜０．０１）。结论：提示ＳＮｘ大鼠早期有肾小管间质ＭＦＢ激活。

关键词：肾硬化肾小管间质MFB α-SMA

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