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| 1 | Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system显示文摘允许的技术内长的基因的特定的规定为基因功能的学习是珍贵的并且在治疗学有大潜力。我们创造了在 CRISPR 上系统,由核酸酶死者 Cas9 (dCas9 ) 蛋白质组成的二部件的 transcriptional 使活跃之物与互补顺序与 transcriptional 激活域和单个指南 RNA (sgRNAs ) 熔化了到基因倡导者。我们证明在 CRISPR 上能高效地以一种悦耳的方式在人和老鼠房间激活外长的记者基因。另外,我们证明在 vivo 的柔韧的记者基因激活能被把系统部件注入老鼠接合子完成。而且,我们证明在 CRISPR 上能激活内长的 IL1RN, SOX2,和 OCT4 基因。最有效的基因激活被对近似倡导者有约束力的 3-4 sgRNAs 的簇完成,建议他们在基因正式就职的 synergistic 行动。显著地,当指向多重基因的 sgRNAs 同时被介绍进房间时,柔韧的多路的内长的基因激活被完成。染色体宽的表示介绍表明了系统的高特性。 | Albert W Cheng Haoyi Wang Hui Yang Linyu Shi Yarden Katz Thorold W Theunissen Sudharshan Rangarajan Chikdu S Shivalila Daniel B Dadon Rudolf Jaenisch | 2013 | Cell Research2013，23，10： | 65 |
| 2 | Structure and function of aggrecan显示文摘Aggrecan is the major proteoglycan in the articular cartilage. This molecule is important in the proper functioning of articular cartilage because it provides a hydrated gel structure (via its interaction with hyaluronan and link protein) that endows the cartilage with load-bearing properties. It is also crucial in chondroskeletal morphogenesis during development. Aggrecan is a multimodular molecule expressed by chondrocytes. Its core protein is composed of three globular domains (G1, G2, and G3) and a large extended region (CS) between G2 and G3 for glycosaminoglycan chain attachment. G1 comprises the amino terminus of the core protein. This domain has the same structural motif as link protein. Functionally, the G1 domain interacts with hyaluronan acid and link protein, forming stable ternary complexes in the extracellular matrix. G2 is homologous to the tandem repeats of G1 and of link protein and is involved in product processing. G3 makes up the carboxyl terminus of the core protein. It enhances glycosaminoglycan modification and product secretion. Aggrecan plays an important role in mediating chondrocyte-chondrocyte and chondrocyte-matrix interactions through its ability to bind hyaluronan. | CHRIS KIANI, LIWEN CHEN, YAO JIONG WU, ALBERT J YEE, BURTON B YANG, Sunnybrook and Women’s College Health Sciences Centre and Department of Laboratory Medicine and Patobiology, 2 Department of Surgeny, Faculty of Medicine, University of Toronto, Canada | 2002 | Cell Research2002，12，1： | 27 |
| 3 | 美国国立老化研究所与阿尔茨海默病协会诊断指南写作组:对阿尔茨海默病诊断指南的推荐和介绍显示文摘背景:尽管早在1984年就制定了阿尔茨海默病(AD)的临床诊断标准,但是近年来的研究进展从未被补充到诊断标准中。因此,制定一个新的临床诊断标准已经成为大家的共识。方法:在2009年,美国国立老化研究所与AD协会组织了一系列圆桌会议,目的是讨论用于AD临床和科研的诊断标准的修订路线。经讨论后决定组建3个独立的工作组,分别制定AD在3个不同疾病发展阶段的诊断标准,即痴呆阶段、有症状的痴呆前期、无症状的临床前期。结果:修订版AD诊断标准与1984年版诊断标准有两处显著的差别:加入了能提示潜在疾病状态的生物标志物的内容;制定了不同认知障碍阶段的诊断标准。其中,3个工作组一致认为,生物标志物的诊断价值还需要更多研究来规范和验证。另外,修订版中还明确区分了仅存在AD病理生理改变(语义性)和仅存在AD临床表现(概念性)两种诊断的差别,该内容在1984年版中没有体现。结论:修订版AD诊断标准中共产生了3个文件,其中,核心的关于AD的痴呆阶段诊断标准和可归于AD的MCI阶段标准推荐用于临床诊断,而临床前期诊断标准仅推荐用于研究使用。 | Jack CR Jr Albert MS Knopman DS McKhann GM Sperling RA Carrillo MC Thies B Phelps CH 贾建平(译) 李丹(译) 閵芳菊(译) 陆璐(译) 张逸驰(译) 黄丽(译) | 2012 | 中华神经科杂志2012，45，5： | 26 |
| 4 | Impact of concomitant use of proton pump inhibitors and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome显示文摘BackgroundThere 是在质子泵禁止者(PPI ) 和 clopidogrel 之间的可能的不利相互作用上的大争论。另外, PPI 的使用是否少些影响 ticagrelor 遗体的临床的功效,知道。在经皮的冠的干预(一种总线标准) .MethodsWe 回顾地从 “ 分析了数据以后,我们试图与急性冠的症候群(交流)在病人在临床的结果上决定 PPI 和 clopidogrel 或 ticagrelor 的伴随物管理的影响;真实 world” ;,国际,在 2003 和 2014 之间的多中心登记( n = 15,401 )并且在1年的合成主要端点上估计了 PPI 和 clopidogrel 或 ticagrelor 的伴随物管理的影响(所有原因死亡收到 PPI 的病人更老,更经常女性,并且是更可能的有 comorbidities。没有协会为收到 clopidogrel 的病人在 PPI 使用和主要端点之间被观察(调整 HR:1.036;95% CI:0.903-1.189 ) 或 ticagrelor (调整 HR:2.320;95% CI:0.875-6.151 )(P 相互作用 = 0.2004 ) 。同样, PPI 的使用没与所有原因死亡,重新梗塞,或与交流后面的一种总线标准的为与任何一个 clopidogrel 对待的病人或 ticagrelor.ConclusionsIn 病人的严重流血的减少的风险的增加的风险被联系, PPI 的伴随物使用没在收到 clopidogrel 或 ticagrelor 的病人与不利结果的增加的风险被联系。我们的调查结果显示与 clopidogrel 或 ticagrelor 在联合使用 PPI 是合理的,特别在有胃肠的流血的更高的风险的病人。 | Yan YAN Xiao WANG Jing-Yao FAN Shao-Ping NIE Sergio Raposeiras-Roubin Emad Abu-Assi Jose P Simao Henriques Fabrizio D'Ascenzo Jorge Saucedo Jose R Gonzfilez-Juanatey Stephen B Wilton Wouter J Kikkert Ivlin Nufiez-Gil Albert Ariza-Sole Xian-Tao SONG Dimitrios Alexopoulos Christoph Liebetrau Tetsuma Kawaji Claudio Moretti Zenon Huczek Toshiharu Fujii Luis C Correia Masa-aki Kawashiril Sasko Kedev | 2016 | Journal of Geriatric Cardiology2016，13，3： | 12 |
| 5 | P2Y12受体抑制剂联合质子泵抑制剂对急性冠脉综合征患者缺血事件影响的临床分析显示文摘目的本研究旨在分析P2Y12受体抑制剂联合质子泵抑制剂(PPI)治疗对经皮冠状动脉介入(PCI)术后的急性冠脉综合征患者缺血事件的影响。方法基于国际多中心回顾性注册登记研究,纳入2003至2014年因急性冠脉综合征人院行PCI术的患者,分为PPI组及非PPI组并随访1年,主要临床终点为全因死亡/再发心肌梗死的复合终点。根据P2Y12受体抑制剂种类,将入组患者分为氯吡格雷组及替格瑞洛组,并比较不同药物与PPI联用发生临床终点事件的风险。结果研究入选9429例患者,PPI组占54.8%,具有更多高危因素。Cox回归结果提示PPI组较非PPI组全因死亡/再发心肌梗死复合事件的发生差异无统计学意义(HR1.00,95%CI 0.86—1.18)。根据P2Y12抑制剂种类不同分为氯吡格雷组和替格瑞洛组,不同P2Y12受体抑制剂联用PPI较未联用PPI患者的临床终点无差异,联用PPI的氯吡格雷组与替格瑞洛组的临床终点差异也无统计学意义。结论急性冠脉综合征患者PPI与P2Y12受体抑制剂联用不增加全因死亡和再发心肌梗死风险,尤其PPI联用氯吡格雷在患者的缺血事件上与替格瑞洛比较差异无统计学意义。 | 冯斯婷 严妍 范婧尧 王晓 郑文 聂绍平 Sergio Raposeiras-Roubin Emad Abu-Assi Jose P Simao Henriques Fabrizio D' Ascenzo Jorge Saucedo Jose R Conzalez-Juanatey Stephen B Wilton Wouter J Kikkert Ivan Nunez-Gil Albert Ariza-Sole Dimitrios Alexopoulos Christoph Liebetrau Tetsuma Kawaji Claudio Moretti Zenon Huczek Toshiharu Fujii Luis C Correia Masa-aki Kawashiri Sasko Kedev | 2016 | 中华医学杂志2016，96，33： | 6 |
| 6 | Impact of triple antithrombotic therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention in real-world practice显示文摘为在急性冠的症候群(交流) 和经皮的冠的干预(一种总线标准) 以后的口头的 anticoagulation (OAC ) 上的病人的 ObjectiveThe 最佳的 antithrombotic 政体仍然保持辩论。寻求回顾地在真实世界的 setting.MethodsWe 评估 OAC 正 clopidogrel 的功效和安全与或没有阿司匹林的这研究分析了数据从一国际,在 2003 和 2014 之间的多中心登记(n = 15,401 ) 。有在一种总线标准以后的交流和收到的 OAC 的病人被屏蔽。合成主要端点是 1 年的所有原因死亡,重新梗塞,或分析注册了 642 个病人包括的严重 bleeding.ResultsThe 期末考试有 OAC 和 clopidogrel (双治疗) 的 62 个病人(9.7%) ,和有阿司匹林, OAC 和 clopidogrel (三倍的治疗) 的联合的 580 个病人(90.3%) 。三倍的治疗上的病人更经常是女性的并且是更可能的有 comorbidities。关于在与三倍的治疗病人一起的双治疗之间的主要结束点没有重要差别[17.74% 对 17.24% ;unadjusted 危险比率(HR ) :1.035;95% 信心间隔(CI ) :0.556-1.929;调整 HR:1.026;95% CI:0.544-1.937 ] 。然而,重新梗塞率比三倍的治疗病人在双治疗是显著地更高的(14.52% 对 5.34% ;unadjusted HR:2.807;95% CI:1.329-5.928;调整 HR:2.333;95% CI:1.078-5.047 ) 。另外,在所有原因死亡和严重 bleeding.ConclusionsIn 的二政体之间没有差别有交流后面的一种总线标准并且与 OAC 的一个指示的真实病人,三倍的治疗没与双治疗相比与不利结果的增加的率被联系。而且,它减少了重新梗塞冒险并且没增加严重流血的风险。 | Yan YAN Xiao WANG Jing-Yao FAN Shao-Ping NIE SerGio Raooseiras-Roubin Emad Abu-Assi Jose P Simao Henriques: Fabrizio D'Ascenzo Jorge Saucedo Jose R Gonzalez-Juanate Stephen B Wilton Wouter J Kikkert Ivan Nunez-Gil Albert Ariza-Sole Xian-Tao SONG Dimitrios Alexopoulos Christoph Liebetrau Tetsuma Kawaji Claudio Morettil Zenon Huczek Toshiharu Fujii Luis cL Correia Masa-aki Kawashiri Sasko Kedev | 2017 | Journal of Geriatric Cardiology2017，14，11： | 6 |
| 7 | Silicon carbide resonant tuning fork for microsensing applications in high-temperature and high G-shock environments显示文摘We present the fabrication and testing of a silicon carbide(SiC)balanced mass double-ended tuning fork that survives harsh environments without compromising the device strain sensitivity and resolution bandwidth.The device features a material stack that survives corrosive environments and enables high-temperature operation.To perform high-temperature testing,a specialized setup was constructed that allows the tuning fork to be characterized using traditional silicon electronics.The tuning fork has been operated at 600 ℃ in the presence of dry steam for short durations.This tuning fork has also been tested to 64 000 G using a hard-launch,soft-catch shock implemented with a light gas gun.However,the device still has a strain sensitivity of 66 Hz/με and strain resolution of 0.045 με in a 10 kHz bandwidth.As such,this balanced-mass double-ended tuning fork can be used to create a variety of different sensors including strain gauges,accelerometers,gyroscopes,and pressure transducers.Given the adaptable fabrication process flow,this device could be useful to micro-electro-mechanical systems(MEMS) designers creating sensors for a variety of different applications. | David R Myers Kan Bun Cheng Babak Jamshidi Robert G Azevedo Debbie G Senesky Li Chen Mehran Mehregany Muthu B J Wijesundara Albert P Pisano | 2012 | Engineering Sciences2012，10，5： | 6 |
| 8 | Correlation between the proportion of breast volume involved by locally advanced tumors and invasion of the skin and posterior structures显示文摘AIM: To evaluate any differences between the percentages of involved breast volume, pathologic attributes,and tumor marker expression of T3 and T4a-c tumors in locally advanced breast cancers(BC).METHODS: All patients with T3 N > 0 and T4a-c BC without evidence of distant metastasis(M0), presenting to the Breast Clinic from 1980 to 2010, were examinedto determine whether their BC's involved ≥ 50% of their breast volumes, defined by gross replacement of at least one hemisphere. Core needle biopsy or postmastectomy specimens from tumors involving a known percent of breast volume were evaluated for:(1)pathological grades and lympho-vascular invasion(LVI);(2) hormone receptor(ER/PR) expression > 0; and(3)epidermoid growth factor 2(her2) over-expression(3+)by immune-histochemical staining or fluorescent in situ hybridization.RESULTS: The data base included 98 patients with T3N> 0 M0 and 120 with T4a-c, any N disease, M0 disease. T3 tumor masses involved 50% or more of the breast in 23/98(24%), and T4a-c tumors 65/120(54%)(P < 0.001). Only 1% of T3 tumors and 23% of T4a-c tumors presented with total breast replacement. There were no significant differences between the pathological attributes and marker expression of the T3 and T4a-c tumors.CONCLUSION: These data suggest that erosion of the overlying skin or underlying chest wall by some BC may be due to neglect and delay, rather than inherent biological aggressiveness. | Parastoo B Dahi Komal P Dhiran Constantine A Axiotis Jeremy Weedon Mahmoud El-Tamer Gurinder Sidhu Albert S Braverman | 2012 | World Journal of Clinical Oncology2012，3，3： | 2 |
| 9 | Pancreaticβ-cell dysfunction in type 2 diabetes:Implications of inflammation and oxidative stress显示文摘Insulin resistance and pancreaticβ-cell dysfunction are major pathological mechanisms implicated in the development and progression of type 2 diabetes(T2D).Beyond the detrimental effects of insulin resistance,inflammation and oxidative stress have emerged as critical features of T2D that defineβ-cell dysfunction.Predominant markers of inflammation such as C-reactive protein,tumor necrosis factor alpha,and interleukin-1βare consistently associated withβ-cell failure in preclinical models and in people with T2D.Similarly,important markers of oxidative stress,such as increased reactive oxygen species and depleted intracellular antioxidants,are consistent with pancreaticβ-cell damage in conditions of T2D.Such effects illustrate a pathological relationship between an abnormal inflammatory response and generation of oxidative stress during the progression of T2D.The current review explores preclinical and clinical research on the pathological implications of inflammation and oxidative stress during the development ofβ-cell dysfunction in T2D.Moreover,important molecular mechanisms and relevant biomarkers involved in this process are discussed to divulge a pathological link between inflammation and oxidative stress duringβ-cell failure in T2D.Underpinning the clinical relevance of the review,a systematic analysis of evidence from randomized controlled trials is covered,on the potential therapeutic effects of some commonly used antidiabetic agents in modulating inflammatory makers to improveβ-cell function. | Phiwayinkosi V Dludla Sihle E Mabhida Khanyisani Ziqubu Bongani B Nkambule Sithandiwe E Mazibuko-Mbeje Sidney Hanser Albert Kotze Basson Carmen Pheiffer Andre Pascal Kengne | 2023 | World Journal of Diabetes2023，14，3： | 2 |
| 10 | 遗传性肥胖与心房颤动的关系显示文摘观察性研究已经确定了体质量指数(body mass index,BMI)与心房颤动之间的关联。然而,从观察性研究中推断因果关系会受到混杂因素、逆因果关系和偏倚的影响。该研究的主要目的是应用BMI的遗传学预测因子评估BMI与心房颤动之间的因果关系。方法:纳入1987-2002年期间在美国、冰岛和荷兰实施的7个前瞻性人群队列研究中基线无心房颤动的欧洲血统个体51 646人, | 刘莉 叶鹏 Chatterjee NA Giulianini F Geelhoed B Lunetta KL Misialek JR Niemeijer MN Rienstra M Rose LM Smith AV Arking DE Ellinor PT Heeringa J Lin H Lubitz SA Soliman EZ Verweij N Alonso A Benjamin EJ Gudnason V Stricker BH van der Harst P Chasman DI Albert CM | 2017 | 中华高血压杂志2017，25，2： | 2 |
| 11 | Benthic fluxes and porewater concentration profiles of dissolved organic carbon in sediments from the North Carolina continental slope显示文摘 | Alperin M J Martens C S Albert D B | 1999 | Geochimica et Cosmochimica Acta1999，63，： | 1 |
| 12 | Multicolored hamilton cycles显示文摘 | ALBERT M FRIEZE A REED B | 1995 | Electronic J Combin1995，2，： | 1 |
| 13 | The biology of NKT cells 显示文摘 | Albert B Paul BS Luc T | 2007 | Annu Rev ImmunoL2007，25，： | 1 |
| 14 | In vivo imaging of quantum dots encapsulated in phospholipid micelles显示文摘 | DUBERTRET B SKOURIDES P ALBERT L | 2002 | Science2002，298，5599： | 1 |
| 15 | The large-scale organization of metabolic networks 显示文摘 | Jeong H Tombor B Albert R Oltvai Z Barabasi AL | 2000 | Nature (S0028-0836)2000，407，6804： | 1 |
| 16 | Methane combustion over La2O3-based catalysts and γ-Al2O3显示文摘 | Todd J Toops Arden B Walters M Albert Vannice | 2002 | Applied Catalysis A:General2002，233，： | 1 |
| 17 | Directed evolution of ionizing radiation resistance in Escherichia coli 显示文摘 | Harris D R Pollock S V Wood E A Goiffon R J Klingele A J Cabot E L Schackwitz W Martin J Eggington J Durfee T J Middle C M Norton J E Popelars M C Li H Klugman S A Hamilton L L Bane L B Pennacchio L A Albert T J Perna N T Cox M M Battista J R | 2009 | Journal of Bacteriology2009，191，16： | 1 |
| 18 | Anammox sludge immobilized in polyvinyl alcohol (PVA) cryogel carriers显示文摘 | Magri Albert Vanotti Matias B SzOgi Ariel A | 2012 | Biore- sour Teehnol2012，114，： | 1 |
| 19 | Analysis of the safety and efficacy of intra-arterial thrombolytic therapy in ischemic stroke显示文摘 | Jovanovic B D Alberts M J | 2002 | Stroke2002，33，12： | 1 |
| 20 | Consequences of cell death:exposure to necrotic tumor cells,but not primary tissue cells or apoptotic cells显示文摘 | Sauter B Albert ML Francisco L | 2000 | J Exp Med2000，191，3： | 1 |
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