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Pharmacological applications of a novel neoepitope antibody to a modified amyloid precursor protein-derived beta-secretase product

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Protein & Cell 2011年第7期2卷 573-584页

作者： Guoxin Wu Sethu Sankaranarayanan Donna L.Montgomery Adam j.simon Zhiqiang An Mary j.Savage Department of Neurology Merck Research LaboratoryWest PointPA 19486USA Department of Biologics Research Merck Research LaboratoryWest PointPA 19486USA

We have previously described a novel artificial NFEVβ-secretase(BACE1)cleavage site,which when introduced into the amyloid-βprecursor protein(APP),significantly enhances APP cleavage by BACE1 in in vitro and cellular *** this study,we describe the identification and characterization of a single chain fragment of variable region(scFv),specific to the EV neo-epitope derived from BACE1 cleavage of the NFEV-containing peptide,and its conversion to *** the scFv displayed on phage and EV-IgG1 show exquisite specificity for binding to the EV neoepitope without cross-reactivity to other NFEV containing peptides or WT-APP KMDA cleavage ***-IgG1 can detect as little as 0.3 nmol/L of the EV ***-IgG1 antibody was purified,conjugated with alkaline phosphatase and utilized in various biological *** the BACE1 enzymatic assay using NFEV substrate,a BACE1 inhibitor MRK-3 inhibited cleavage with an IC50 of 2.4 nmol/L with excellent *** an APP_NFEV stable SH-SY5Y cellular assay,the EC_(50) for inhibition of EV-Aβ peptide secretion with MRK-3 was 236 nmol/L,consistent with values derived using an EV polyclonal *** an APP_NFEV knock-in mouse model,both Aβ_EV40 and Aβ_EV42 peptides in brain homogenate showed excellent gene dosage *** conclusion,the EV neoepitope specific monoclonal antibody is a novel reagent for BACE1 inhibitor discovery for both in vitro,cellular screening assays and in vivo biochemical *** methods described herein are generally applicable to novel synthetic substrates and enzyme targets to enable robust screening platforms for enzyme inhibitors.

关键词： scFv antibody BACE1 amyloid-βprecursor protein(APP) immunoassay

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Windows 2000 API超级宝典

丛书名：计算机技术译林精选系列

2001年

作者：（美）Richard j.simon 潇湘工作室译

本书是一本完整而详尽的Windows 2000API参考书。书中每章介绍一个编程主题，并在同一章给出与主题编程相关的大量函数及函数说明。

ISBN: (纸本)7115092397

本书是一本完整而详尽的Windows 2000API参考书。书中每章介绍一个编程主题，并在同一章给出与主题编程相关的大量函数及函数说明。

关键词：窗口软件网络服务器

来源：畅想之星图书光盘版（南... 评论

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有点作用的抛物型方程解的控制(英文)

系统科学与数学 1983年第1期 1-27页

作者： j.simon

本文讨论状态由右端有空间点作用的抛物型偏微分方程确定的控制问题。具体地说,给定Ω（Ω为R~n的开集）中的点b,以及（0,T）上的函数v=v（t）,状态y=yv,b（x,t）是下列方程的解: （y/t）+Ay=v（t）δb（t）,x∈Ω,t∈（0,T）,这里假设... 详细信息

本文讨论状态由右端有空间点作用的抛物型偏微分方程确定的控制问题。具体地说,给定Ω（Ω为R~n的开集）中的点b,以及（0,T）上的函数v=v（t）,状态y=yv,b（x,t）是下列方程的解: （y/t）+Ay=v（t）δb（t）,x∈Ω,t∈（0,T）,这里假设y的初值和边值都是零,δb是支点为b的Dirac函数,A是x的二阶椭圆型偏微分算子.被极小化的代价泛函为其中z给定在Ω中,N>0。这一问题是由Lions首先提出并研究的（也参看[10]-[12],[14],[15]）.本文对此又作进一步系统讨论,特别是改正了原来的一些不准确的结果.例如,引入空间 Ub={v|v∈L2（0,T）,yv,b（·,T）∈L2（Ω）}.本文指出而不是以前所指出的本文也指出,Green公式一般也不成立,而应该是这里Q=Ω×（0,T）,∑为Q的边界,A*为A的共轭算子,vA是关于A的外法线方向. 同时,本文还讨论了最优性的一阶必要条件,正则性结果;引入（b）=inf j（v,b）,v∈Ub.还讨论了对b的连续性、可导性、导数在边界上的性态以及对控制问题的应用等。

关键词：一宁

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乳酸盐积聚与无氧阈和呼吸代偿阈的关系

扬州大学学报(自然科学版) 1984年第2期 86-91页

作者： j.simon 杨广鉴

正常而未经训练的受试者以最大耗氧量(Vo)的50—60％的强度进行加功测试(IW)时,每分肺通气量(V)和耗氧量(Vo)并不是成比例的增加。传统的理论认为,V的这种非线性增加是以代谢性酸中毒为基础的。因此,通常所说的无氧阈(AT)是指“乳酸盐... 详细信息

正常而未经训练的受试者以最大耗氧量(Vo)的50—60％的强度进行加功测试(IW)时,每分肺通气量(V)和耗氧量(Vo)并不是成比例的增加。传统的理论认为,V的这种非线性增加是以代谢性酸中毒为基础的。因此,通常所说的无氧阈(AT)是指“乳酸盐开始在血液中积聚而引起代谢性酸中毒的最大耗氧量。”在很大强度的IW时,代谢性

关键词：乳酸盐无氧血浆 AT 受试者最大功率

A good gut feeling on Sarml-mediated axon degeneration

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Protein & Cell 2021年第8期12卷 596-598页

作者： Victoria E.von Saucken David j.simon Department of Biochemistry Weill Cornell Medical College1300 York AvenueNew YorkNY 10065USA Tri-lnstitutional MD-PhD Program Weill Cornell MedicineRockefeller UniversityMemorial Sloan Kettering Cancer Center1300 York AvenueNew YorkNY 10065USA

关键词： degeneration chemotherapy traumatic

In situ characterization of particle formation in spray flame synthesis using wide-angle light scattering

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Particuology 2024年第3期86卷 304-312页

作者： simon Aβmann Franz j.T.Huber Stefan Will Lehrstuhl für Technische Thermodynamik(LTT) Friedrich-Alexander-Universitat Erlangen-Nürnberg(FAU)Erlangen91058Germany Erlangen Graduate Schoolin Advanced Optical Technologies(SAOT) Friedrich-Alexander-Universitat Erlangen-Nurnberg(FAU)Erlangen91052Germany Competence Unit Engineering of Advanced Materials(EAM) Friedrich-Alexander-Universitat Erlangen-Nürnberg(FAU)Erlangen91052Germany

Wide-angle light scattering(WALS)was used for in situ measurements of droplet and nanoparticle size distributions during the synthesis of titania and iron oxide particles from liquid precursor solutions in the standardized SpraySyn burner for spray flame *** was synthesized from titanium tetraisopropoxide(TTIP)and iron oxide from iron(II)nitrate nonahydrate(INN)using ethanol(EtOH)as *** images were taken at heights up to 120 mm above the burner surface and classified into droplet and particle *** size distributions were derived from a sequential analysis of scattering data containing the oscillating Mie pattern,the lognormal size distribution parameters for spherical and fractal particle fractions from a multivariate approach on averaged particle scattering *** results show that the precursor addition leads to altered evaporation behavior and even droplet disruption probably induced by puffing or micro-explosions compared to pure *** the case of TTIP(a hygroscopic alkoxide),the synthesis of a large fraction of spheres was observed,while the nitrate INN leads to the formation of mostly fractal aggregates.

关键词： Spray flame synthesis Metal oxide particles Elastic light scattering Droplet size distribution Nanoparticle morphology Particle size distribution

Machine learning ensemble model prediction of northward shift in potato cyst nematodes(Globodera rostochiensis and ***)distribution under climate change conditions

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journal of Integrative Agriculture 2024年第10期23卷 3576-3591页

作者： Yitong He Guanjin Wang Yonglin Ren Shan Gao Dong Chu simon j.McKirdy Shandong Engineering Research Centre for Environment-friendly Agricultural Pest Management College of Plant Health andMedicineQingdao Agricultural UniversityQingdao 266109China Harry Butler Institute Murdoch UniversityMurdochWA 6150Australia School of Information Technology Murdoch UniversityPerthWA 6150Australia Hebei Dahaituo National Nature Reserve Management Centre Chicheng 075500China

Potato cyst nematodes(PCNs)are a significant threat to potato production,having caused substantial damage in many *** the future distribution of PCN species is crucial to implementing effective biosecurity strategies,especially given the impact of climate change on pest species invasion and *** learning(ML),specifically ensemble models,has emerged as a powerful tool in predicting species distributions due to its ability to learn and make predictions based on complex data ***,this research utilised advanced machine learning techniques to predict the distribution of PCN species under climate change conditions,providing the initial element for invasion risk *** first used Global Climate Models to generate homogeneous climate predictors to mitigate the variation among ***,five machine learning models were employed to build two groups of ensembles,single-algorithm ensembles(ESA)and multi-algorithm ensembles(EMA),and compared their *** this research,the EMA did not always perform better than the ESA,and the ESA of Artificial Neural Network gave the highest performance while being *** results indicated that the distribution range of PCNs would shift northward with a decrease in tropical zones and an increase in northern ***,the total area of suitable regions will not change significantly,occupying 16-20%of the total land surface(18%under current conditions).This research alerts policymakers and practitioners to the risk of PCNs’incursion into new ***,this ML process offers the capability to track changes in the distribution of various species and provides scientifically grounded evidence for formulating long-term biosecurity plans for their control.

关键词： invasive species distribution future climates homogeneous climate predictors single-algorithm ensembles multi-algorithm ensembles artificial neural network

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钙化评分:一种用来预测是否需要额外的或替代的冠状动脉CT血管成像的个体概率评估

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国际医学放射学杂志 2020年第6期 751-751页

作者：梁演婷 j.simon L.Száraz B.Szilveszter A.Panajotu á.jermendy A.Bartykowszki MTA-SE Cardiovascular Imaging Research Group Heart and V ascular Center Semmelweis University

摘要目的评估在冠状动脉血管成像(CTA)的影像质量不足以做出诊断和/或管腔存在显著狭窄的情况下,人体测量学、临床危险因素和冠状动脉钙化评分(CACS)能否预

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Effects of a school-based karate intervention on academic achievement,psychosocial functioning,and physical fitness:A multi-country cluster randomized controlled trial

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journal of Sport and Health Science 2024年第1期13卷 90-98页

作者： Tania Pinto-Escalona Erica Gobbi Pedro L.Valenzuela simon j.Bennett Pierluigi Aschieri Manuel Martin-Loeches Antonio Paoli Oscar Martinez-de-Quel Faculty of Education Complutense University of MadridMadrid 28040Spain Department of Biomolecular Sciences University of Urbino“Carlo Bo”Urbino 61029Italy Department of Systems Biology University of AlcaláMadrid 28805Spain Research Institute for Sport and Exercise Sciences Faculty of ScienceLiverpool John Moores UniversityLiverpoolL33AFUK Italian judo WrestlingKarate and Martial Arts FederationRome 00122Italy Psychobiology&Methods for the Behavioural Sciences Department Complutense University of MadridMadrid 28040Spain Department of Biomedical Sciences University of PaduaPadua 35122Italy

Purpose:To examine the effects of a school-based karate intervention on academic achievement,psychosocial functioning,and physical fitness in children aged 7-8 ***:Twenty schools in 5 different European countries(2 second-grade classrooms per school)participated in a cluster randomized controlled trial(Sport at School trial).Participants were assigned to either a control group,which continued with their habitual physical education lessons,or to an intervention group,which replaced these lessons with a 1-year karate intervention(Karate Mind and Movement program).A total of 721 children(344 girls and 377 boys,7.4±0.5 years old,mean±SD)completed the study,of which 333 and 388 were assigned to the control group and intervention group,*** included academic performance(average grade),psychosocial functioning(Strengths and Difficulties Questionnaire for parents),and different markers of physical fitness(cardiorespiratory fitness,balance,and flexibility).Results:The intervention provided small but significant benefits compared to the control group for academic achievement(d=0.16;p=0.003),conduct problems(d=-0.28;p=0.003),cardiorespiratory fitness(d=0.36;p0.05).Conclusion:A 1-year school-based karate intervention was effective in improving academic achievement,conduct problems,and physical fitness in primary school *** results support the inclusion of karate during physical education lessons.

关键词： Academic performance Cardiorespiratory fitness Conduct problems Karate Physical fitness

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