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CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through mYC degradation

Signal transduction and targeted therapy 2024年第8期9卷 3519-3532页

作者： Alvaro Quintanal-Villalonga Kenta Kawasaki Esther Redin Fathema Uddin Swanand Rakhade Vidushi Durani Amin Sabet moniquetta Shafer Wouter R.Karthaus Samir Zaidi Yingqian A.Zhan Parvathy manoj Harsha Sridhar Dennis Kinyua Hong Zhong Barbara P.mello metamia Ciampricotti Umesh K.Bhanot Irina Linkov Juan Qiu Radhika A.Patel Colm morrsey Sanjoy mehta Jesse Barnes michael C.Haffner Nichlas D.Socci Richard P.Koche Elisa de Stanchina Sonia molina-Pinelo Sohrab Salehi Helena A.Yu Joseph m.Chan Charles m.Rudin Department of medicine Thoracic Oncology ServiceMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Cancer Biology and Genetics Program Sloan Kettering InstituteMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Vagelos College of Physicians and Surgeons Columbia UniversityNew YorkNYUSA Weill Cornell Graduate School of medical Sciences Weill Cornell MedicineNew YorkNYUA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Center for Epigenetics Research Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Pathology Core Facilty Department of Pathology and Laboratory MedicineMSKCCNew YorkNYUSA Antitumor Assessment Core Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Divisionsof Human Biology and Clinical Research Fred Hutchinon Cancer CenterSeattleWAUSA Deparmentof Urology University of WashingtonSeattleWAUSA Gene Editing&Screening Core Facility memorial Sloan Kettering Cancer Center New YorkNYUSA Department of Laboratory medicine and Pathology University of WashingtonSeattleWAUSA Bioinfomatics CoreFacility Memorial Soan Kettering Cancer CenterNew YorkNYUSA Institute of Biomedicine of Seille(Bis) HURCSCUniversidad de SevillaSevilleSpain Computational Oncology Department of Epidemiology and BiostatisticsMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Well Cornell medical College New York NYUSA Present address:Swiss Institute for Experimental Cancer Research(ISREC) School of Life SciencesEPFLLausanneSwitzerland

Neuroendocrine(NE)transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor *** to date,even if patients at high risk of transformation can be identified by the occurrence of tumor Protein P53(tP53)and Retinoblastoma transcriptional Corepressor 1(RB1)mutations in their tumors,no therapeutic strategies are available to prevent or delay histological *** of the cell cycle kinase Cell Division Cycle 7(CDC7)occurred in tumors during the initial steps of NE transformation,already after tP53/RB1 co-inactivation,leading to induced sensitivity to the CDC7 inhibitor ***7 inhibition suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation by inducing the proteasome-mediated degradation of the mYC Proto-Oncogen(mYC),implicated in stemness and histological *** overexpression of a degradation-resistant mYC isoform reestablished the NE transformation phenotype observed on targeted therapy,even in the presence of ***7 inhibition also markedly extended response to standard cytotoxics(cisplatin,irinotecan)in lung and prostate small cell carcinoma *** results nominate CDC7 inhibition as a therapeutic strategy to constrain lineage plasticity,as well as to effectively treat NE tumors de novo or after *** simurosertib clinical efficacy trials are ongoing,this concept could be readily translated for patients at risk oftransformation.

关键词： tumors markedly transformation

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基线舒张压对标准降压和强化降压效果的影响

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中华高血压杂志 2017年第12期25卷 1182-1184页

作者： Beddhu S Chertow Gm Cheung AK Cushman WC Rahman m Greene t Wei G Campbell rc Conroy m Freedman BI Haley WE Horwitz EJ Kitzman DW Lash J Papademetriou V Pisoni R Riessen E Rosendorff C Watnick SG Whittle J Whelton PK medical Service Veterans Affairs Salt Lake City Health Care System UT (S.B. A.K.C.) srinivasan.beddhu@hsc.utah.edu. Division of Nephrology and Hypertension (S.B. A.K.C. G.W.). University of Utah School of medicine Salt Lake City. Stanford University Palo Alto CA (G.M.C.). medical Service Veterans Affairs Salt Lake City Health Care System UT (S.B. A.K.C.). Veterans Affairs medical Center Memphis TN (W.C.C.). Case Western Reserve University Cleveland OH (M.R. E.H.). Division of Biostatistics (t.G.). medical University of South Carolina Charleston (R.C.C. R.P.). Division of General Internal medicine (m.C.). Section on Nephrology (B.I.F.). Wake Forest School of medicine Winston-Salem NC. Division of Nephrology and Hypertension Mayo Clinic Jacksonville FL (W.H.). metrohealth medical Center Cleveland OH (E.H.). Section on Cardiology (D.K.). University of Illinois at Chicago IL (J.L.). Division of Cardiology Veterans Administration Medical Center Washington DC (V.P.). Ralph H. Johnson VA medical Center Charleston SC (R.P.). Intermountain medical Center Murray UT (E.R.). Icahn School of medicine at mount Sinai New York NY (C.R.). Oregon State Health University Portland (S.G.W.). Primary Care Division Clement J. Zablocki VA Medical Center Milwaukee WI (J.W.). tulane University School of Public Health and tropical medicine New Orleans LA (P.K.W.).

血压升高是心血管病、终末期肾病（end—stage kidney disease，ESKD）和全因死亡的一个重要危险因素。自20世纪60年代开始，随机对照试验证明了治疗高舒张压，随后又证明了治疗高收缩压的价值。

关键词：降压效果舒张压标准基线随机对照试验终末期肾病心血管病血压升高

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Utilizing the ultrasensitive Schistosoma up-converting phosphor lateral flow circulating anodic antigen(UCP-LF CAA)assay for sample pooling-strategies

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Infectious Diseases of Poverty 2017年第1期6卷 1379-1391页

作者： Paul L.A.m.Corstjens Pytsje t.Hoekstra Claudia J.de Dood Govert J.van Dam Department of molecular Cell Biology Leiden University Medical CenterP.O.Box 96002300RCLeidenThe Netherlands Department of Parasitology Leiden University Medical CenterP.O.Box 96002300RCLeidenThe Netherlands

Background:methodological applications of the high sensitivity genus-specific Schistosoma CAA strip test,allowing detection of single worm active infections(ultimate sensitivity),are discussed for efficient utilization in sample pooling *** relevant cost reduction,pooling of samples rather than individual testing can provide valuable data for large scale mapping,surveillance,and ***:the laboratory-based CAA strip test utilizes luminescent quantitative up-converting phosphor(UCP)reporter particles and a rapid user-friendly lateral flow(LF)assay *** test includes a sample preparation step that permits virtually unlimited sample concentration with urine,reaching ultimate sensitivity(single worm detection)at 100%*** facilitates testing large urine pools from many individuals with minimal loss of sensitivity and *** test determines the average CAA level of the individuals in the pool thus indicating overall worm burden and *** requiring test results at the individual level,smaller pools need to be analysed with the pool-size based on expected prevalence or when unknown,on the average CAA level of a larger group;CAA negative pools do not require individual test results and thus reduce the number of ***:Straightforward pooling strategies indicate that at sub-population level the CAA strip test is an efficient assay for general mapping,identification of hotspots,determination of stratified infection levels,and accurate monitoring of mass drug administrations(mDA).At the individual level,the number of tests can be reduced *** low endemic settings as the pool size can be increased as opposed to prevalence ***:At the sub-population level,average CAA concentrations determined in urine pools can be an appropriate measure indicating worm *** strategies allowing this type of large scale testing are feasible with the various CAA strip test formats and do not affect sens

关键词： Schistosomiasis Diagnostics Sample pooling mass drug administration Circulating anodic antigen Lateral flow Strip test Up-converting reporter particle UCP-LF CAA

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Some aspects affecting the response of rc compartment structures subjected to internal blast loads

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Earthquake Engineering and Engineering Vibration 2022年第1期21卷 135-148页

作者： Osman m.O.Ramadan m.Galal El Sherbiny Ahmed m.Khalil Faculty of Engineering Cairo UniversityCairo 12411Egypt Higher technological Institute(HtI)at 10th of Ramadan City Sharqia 13658Egypt Structural Engineering and Construction management Department Faculty of Engineering&TechnologyFutureUniversity in Egypt-FUECairo 16383Egypt

Protective compartments are typically used to protect some specific structures from internal explosions,such as industrial buildings that contain devices that may explode in certain *** research investigates how the response of reinforced concrete(rc)compartment structures subjected to internal blast loads are affected by the following aspects:introduction of material nonlinearity in the analysis,reinforcement ratio,and aspect ratio of the *** achieve this goal,a calibrated and sophisticated FE numerical model is introduced,and a parametric study for the intended aspects is carried out.A discussion of the results and conclusions are offered,which show the role of each aspect in the dynamic performance of the compartment *** main conclusions are as follows:introduction of material nonlinearity in this type of analysis and for these structures is very important and significant in obtaining accurate outputs that are similar to actual behavior;the reinforcement ratio has a significant effect on the response and its effect varies depending on the thickness of the compartment;in general,increasing the reinforcement ratio enhances the behavior and reduces the stresses in the compartment;and the aspect ratio of the compartment does not show a clear pattern on the response of such structures under internal blast loads.

关键词： blast loads protective structures nonlinear analysis explicit dynamic analysis

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Residual drift spectra for rc bridge columns subjected to near-fault earthquakes

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Earthquake Engineering and Engineering Vibration 2021年第1期20卷 193-211页

作者： S.m.Seyed Ardakani m.Saiid Saiidi Paul Somerville Department of Civil and Environmental Engineering Ohio Northern University525 S.Main St.AdaOH 45810USA Department of Civil and Environmental Engineering University of NevadaRenoMS 258RenoNV 89557USA AECOm technology Corporation One California Plaza300 S Grand AvenueLos AngelesCA 90017USA

Permanent displacement of a bridge column can be directly measured during the inspection after near-fault ***,the engineer needs to estimate the expected residual drift at the design stage to determine if the bridge seismic performance is *** most direct method to estimate the residual displacement is nonlinear response history analysis,which is time consuming and ***,an attractive but indirect method is generating estimated residual displacement spectra that depend on displacement ductility demand,column period,site conditions,and earthquake *** the period and the expected displacement ductility demand for the column,the residual drift response spectra curves can be utilized to estimate the residual drift *** drift spectra that are applicable to rc bridge columns in different parts of the United States were developed based on nonlinear response history analyses using a comprehensive collection of recorded and synthetic near-fault ground motions and were linked to one-second spectral acceleration(S1)of the AASHtO *** was also found that the residual drift ratio is below one percent when S1 is less than 0.6 g.

关键词： near-fault earthquake reinforced concrete bridge column residual displacement

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A novel deadline and budget constrained scheduling heuristics for computational grids

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Journal of Central South University 2011年第2期18卷 465-472页

作者：王勇 R.m.BAHAtI m.A.BAUER School of Computer Science China University of Geosciences Department of Computer Science University of Western Ontario

the conventional deadline and budget constrained （DBC） scheduling heuristics for economic-based computational grids does not take the inconsistency of grid heterogeneity into account, which can lead to decline of application completion ratios. motivated by this fact, a novel DI3C scheduling heuristics was proposed to deal with sequential workflow applications. In order to valuate the inconsistency, the relative cost （rc） metric was introduced, which was used to indicate the task-starving degree for resources. the new algorithm assigns tasks to resources, considering completion time, budget and rc together. the GridSim toolkit and the benchmark suites of the standard performance evaluation corporation （SPEC） were used to simulate the heterogeneous grid environment and applications. the experimental results show that the task and workflow completion ratios of the new heuristics are higher than those of the conventional heuristics.

关键词： computional grids economic-based grid grid brocker grid scheduling simulation

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the Iberian Roma Population Variant Server(IRPVS)

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Journal of Genetics and Genomics 2024年第7期51卷 769-773页

作者： Fabiola mavillard Javier Perez-Florido Francisco m.Ortuño Amador Valladares miren L.Álvarez-Villegas Gema Roldán Rosario Carmona manuel Soriano Santiago Susarte Pilar Fuentes Daniel López-López Ana maría Nuñez-Negrillo Alejandra Carvajal Yolanda morgado Daniel Arteaga Rosa Ufano Pablo mir Juan F.Gamella Joaquín Dopazo Carmen Paradas macarena Cabrera-Serrano Instituto de Biomedicina de Sevilla(IBiS) Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaSpain Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud CarlosⅢSevillaSpain Plataforma Andaluza de medicina Computacional Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevillaSpain Grupo de medicina computacional de sistemas Instituto de Biomedicina de Sevilla(IBiS)Hospital Virgen del RocíoSevillaSpain Nodo de Genómica Funcional (INB-ELIXIR-es)Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevilla 41013Spain Bioinformática en Enfermedades raras(BiER) Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER)Instituto de salud CarlosⅢSevillaSpain Departamento de Ingeniería de Computadores Automática y RobóticaUniversidad de GranadaGranadaSpain Servicio de Urgencias de Atención Primaria Distrito SevillaSevillaSpain Centro de Servicios Sociales Negociado de Servicios EspecializadosAyuntamiento de SevillaSevillaSpain Departamento de Enfermería Facultad de Ciencias de la SaludUniversidad de GranadaGranadaSpain Departamento de Neurología Hospital Virgen de las NievesGranadaSpain Departamento de Neurología Hospital Virgen de ValmeSevillaSpain Centro de Salud Utrera Sur SevillaSpain Centro de Salud Polígono Sur SevillaSpain Unidad de trastornos del movimiento Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain Departamento de medicina Facultad de MedicinaUniversidad de SevillaSevilleSpain Departamento de Antropología Social Universidad de GranadaSpain Unidad Enfermedades Neuromusculares Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain

In recent years,the number of known disease genes has exponentially grown due to the widespread adoption of cost-effective massive parallel *** identify new disease variants,especially in monogenic disorders,a frequen... 详细信息

关键词： Server filtering massive

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the effect of ozone and drought on the photosynthetic performance of canola

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Journal of Integrative Agriculture 2018年第5期17卷 1137-1144页

作者： Bheki G maliba Prabhu m Inbaraj Jacques m Berner Unit for Environmental Sciences and management North-West University Eskom Research Testing and Development Department of Chemistry School of ScienceRK University

Canola plants were fumigated in open-top chambers with ozone（O3）（120 ppb）under well-watered（WW）and water-stressed（WS）conditions for 4 ***-fumigated plants were also studied to facilitate comparison between treatments for the same week and over ***,the treatments were：WW,WW-O3,WS and *** fast chlorophyll a fluorescence transients OJIP for the four treatments emitted upon illumination of dark-adapted leaves were measured after week 1,2,3,4 and analysed by the JIP-test to evaluate the resulting changes in photosynthetic *** fumigation led to a decline of total performance index（PI（total））in well-watered *** effect of O3 was minor under drought conditions,as revealed by a decrease of PI（total） by 3%.the PI（total） decreased as the treatment was prolonged,due to leaf ageing for all cases and the decline was more pronounced under *** the average of all weeks,WW had the highest PI（total)and the lowest WW-O3（decrease by 27%）,while in WS and WS-O3,it was lower than WW（14 and 17%,respectively）.We found that the absorption（ABS）/reaction centre（rc）increases,while the maximum quantum yield of primary photochemistry（φ（Po））undergoes slight changes,and trapping（tR0）/rc closely followed the increase in ABS/*** indicates that O3and drought caused an increase in the functional antenna *** maximum quantum yield of primary photochemistry showed slight differences for all treatments and over time,suggesting that this parameter is less sensitive to drought and O3 ***,the more sensitive components of the photosynthetic electron transport chain appeared to be the probability that an electron from the intersystem electron carriers is transferred to reduce end electron acceptors at the PSI acceptor side（δ（Ro））and the rc density on a chlorophyll basis（rc/ABS）.

关键词： canola Chl a fluorescence JIP-test open-top chamber ozone

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口服降糖药和胰岛素对眼表治疗的影响(英文)

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国际眼科杂志 2013年第9期13卷 1747-1750页

作者： Burin Kklü akιr Yasemin Aslan Katιrcιoglu Nurten nlü Hüseyin stün Remzi Kasιm Sunay Duman Bahcelievler市Orkide大街39/5号土耳其巴勒克埃西尔10050 安卡拉培训和研究医院眼科土耳其安卡拉06600

目的:描述和对比口服降糖药(OAD)和胰岛素治疗2型糖尿病患者眼表的效果。方法:在安卡拉卫生部培训和研究医院就诊的20例40眼口服降糖药患者,20例40眼胰岛素治疗患者,对照组的10例非糖尿病人作为研究对象。对所有患者进行常规眼科检查,Sc... 详细信息

目的:描述和对比口服降糖药(OAD)和胰岛素治疗2型糖尿病患者眼表的效果。方法:在安卡拉卫生部培训和研究医院就诊的20例40眼口服降糖药患者,20例40眼胰岛素治疗患者,对照组的10例非糖尿病人作为研究对象。对所有患者进行常规眼科检查,Schirmer试验,泪膜破裂时间分析和结膜印迹细胞学分析.比较三组的泪液功能参数,杯状细胞密度和鳞状上皮化生等级。记录视网膜病变及眼表疾病之间的关系。结果:口服降糖药患者泪膜破裂时间值明显低于其他组(P<0.05)。三组的杯状细胞密度和鳞状上皮化生等级相近。上皮细胞稍大,呈现更多的多边形的眼的中位数级为1级,并且嗜酸性染色胞浆和杯状细胞数量减少。视网膜病变与眼表疾病不相关。结论:口服降糖药患者的角膜前泪膜稳定性比其他组差。各组的印迹细胞学分析结果相似。

关键词：眼表糖尿病印迹细胞学

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澳大利亚临床共识指南:儿童卒中的诊断和急性期处理

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中国脑血管病杂志 2019年第4期16卷 218-224页

作者： medley tL miteff C Andrews I Ware t Cheung m monagle P mandelstam S Wray A Pridmore C troedson C Dale rc Fahey m Sinclair A Walsh P Stojanovski S macka mt 徐佳丽(译) 吴川杰(译) 肖潇(译) 吕俊萱(译) 张博维(译) 吉训明(译) 不详首都医科大学宣武医院神经内科北京100053 苏州大学儿童医院神经内科

卒中是导致儿童死亡的十大原因之一,幸存的致残患儿将面临几十年的残疾生活,给患儿及其家庭带来了巨大负担。由于安全性和有效性的证据有限,以及诊断的延误,目前卒中患儿无法接受再灌注治疗。儿童卒中诊断和急性期处理的澳大利亚临床共... 详细信息

卒中是导致儿童死亡的十大原因之一,幸存的致残患儿将面临几十年的残疾生活,给患儿及其家庭带来了巨大负担。由于安全性和有效性的证据有限,以及诊断的延误,目前卒中患儿无法接受再灌注治疗。儿童卒中诊断和急性期处理的澳大利亚临床共识指南,旨在最大限度地减少临床诊疗中的不确定性,并记录与成人卒中不同的危险因素、病因和假性卒中情况的最佳证据。临床问题的阐述来自于对2007年至2017年数据库的系统检索,但仅限于英语和儿科研究。该指南应用SIGN方法和国家健康与医学研究委员会系统对证据进行筛选和分类,通过推荐、评估、发展和评价系统(GRADE系统)对推荐进行强弱分级。该指南提供了60多项基于证据的推荐,以帮助参与院前和急症处理的临床医师快速识别儿童卒中,选择最合适的初步检查方案来确定诊断、明确病因,并选择最恰当的干预措施以挽救脑组织、预防复发。同时,指南也提供了颅内压和先天性心脏病管理方面的推荐。该指南的实施需要将院前和急诊系统重组,包括建立区域性卒中网络,建立儿科卒中疾病编码,快速mRI,以及对能够提供再灌注治疗的初级儿科卒中中心进行认证。该指南能够审核治疗的基准时间线,获得急性期的干预措施及预后判断。它还将促进澳大利亚儿童卒中登记的发展,并与国际登记处建立数据联系,以便准确收集卒中发病率、治疗和结果相关的数据。

关键词：急性儿童卒中临床指南管理儿科方案

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