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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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Continuity of care by a primary midwife(caseload midwifery):a cost analysis using results from the COSMOS randomised controlled trial

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Gynecology and Obstetrics Clinical Medicine 2024年第2期4卷 94-101页

作者： Emily j Callander Hannah jackson Helen L McLachlan mary-Ann Davey Della A Forster University of Technology Sydney SydneyNew South WalesAustralia The Royal Women's Hospital MelbourneVictoriaAustralia Faculty of Health University of Technology SydneyBroadwayNew South WalesAustralia judith Lumley Centre La Trobe UniversityMelbourneVictoriaAustralia School of Nursing and Midwifery a Trobe UniversityMelbourneVictoriaAustralia Department of Obstetrics and Gynaecology Monash UniversityClaytonVictoriaAustralia

Introduction Caseload midwifery(continuity of midwifery carer)offers benefits including lower caesarean section rates,lower risks of preterm birth and stilbirth,and improved maternal satisfaction of *** these advantages,concerns about additional costs hinder widespread *** study examinesthecost of caseload midwifery compared with standard maternity care from the perspective of both public hospitals and public *** A cost analysis was conducted using data from a randomised controlled trial of 2314 low-risk pregnant women in Melbourne,*** randomised to caseload care received antenatal,intrapartum and postpartum care from a primary midwife,with some care provided by a‘back-up'*** in standard care received midwifery-led care with varying levels of continuity,junior obstetric care or community-based medical *** cost analysis compared differences in mean costs of health resources to public hospitals and to public ***,a budget impact analysis estimated total costs to the health system between 2023 and *** For public hospitals,there was no significant difference in overall costs between women receiving caseload midwifery(n=1146)versus standard care(n=1151)($SA12363(SD:$A4967)vs$A12323(SD:$A7404);p=0.85).Conversely,public funders incurred lower expenditures for women receiving caseload midwifery($A20330(SD:$A8312))versus standard care($A21637(SD:$A11818);p<0.001).The budget impact analysis estimated savings of sA625million to the health system over the next 5 years with expanded access to caseloadmidwifery *** Caseloadmidwifery in low-risk women is cost-neutral to public hospitals and cost-saving to public *** abstract Continuity of midwifery for low-risk women reduces costs to public funders,with no additional costs to hospitals.

关键词： random continuity Continuity

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Older Adult Compendium of Physical Activities:Energy costs of human activities in adults aged 60 and older

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journal of Sport and Health Science 2024年第1期13卷 13-17,F0003页

作者： Erik A.Willis Stephen D.Herrmann mary Hastert Chelsea L.Kracht Tiago V.Barreira john M.Schuna jr. Zhenghua Cai Minghui Quan Scott A.Conger Wendy j.Brown Barbara E.Ainsworth Center for Health Promotion and Disease Prevention University of North Carolina at Chapel HillChapel HillNC 27599USA Kansas Center for Metabolism and Obesity Research The University of Kansas Medical CenterKansas CityKS 66160USA Division of Physical Activity and Weight Management Department of Internal MedicineUniversity of Kansas Medical CenterKansas CityKS 66160USA Clinical Science Division Pennington Biomedical Research CenterBaton RougeLA 70808USA Exercise Science Department Syracuse UniversitySyracuseNY 13244USA School of Exercise&Sport Science Oregon State UniversityCorvallisOR 97331USA School of Exercise and Health Shanghai University of SportShanghai 200438China Department of Kinesiology Boise State UniversityBoiseID 83725USA School of Human Movement and Nutrition Sciences The University of QueenslandSt.LuciaQLD 4072Australia Faculty of Health Sciences and Medicine Bond UniversityGold CoastQLD 4229Australia College of Health Solutions Arizona State UniversityPhoenixAZ 85003USA

Purpose:To describe the development of a Compendium for estimating the energy costs of activities in adults>60 years(OA Compendium).Methods:Physical activities(PAs)and their metabolic equivalent of task(MET)values were obtained from a systematic search of studies published in 4 sport and exercise databases(PubMed,Embase,SPORTDiscus(EBSCOhost),and Scopus)and a review of articles included in the 2011 Adult Compendium that measured PA in older *** values were computed as the oxygen cost(VO_(2),mL/kg/min)during PA divided by 2.7 m L/kg/min(MET_(60+))to account for the lower resting metabolic rate in older ***:We identified 68 articles and extracted energy expenditure data on 427 *** these,we derived 99 unique Specific Activity codes with corresponding MET_(60+)values for older *** developed a website to present the OA Compendium MET_(60+)values:https://***:The OA Compendium uses data collected from adults>60 years for more accurate estimation of the energy cost of PAs in older *** is an accessible resource that will allow researchers,educators,and practitioners to find MET_(60+)values for older adults for use in PA research and practice.

关键词： Energy expenditure Exercise MET Older adults

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Resurgence of dengue in the Philippines

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World journal of Virology 2024年第3期13卷 7-9页

作者： jasmine S Interior Kyrsten jannae j Bigay Remigo Angelo A Iringan mary Beth F Tanco St.Luke's Medical Center College of Medicine-William H.Quasha Memorial Quezon 1112Philippines

The coronavirus disease 2019(COVID-19)pandemic has significantly influenced the epidemiological landscape of various infectious diseases such as *** is an endemic disease in the Philippines,which showed a significant de-cline in the number of cases beginning in March 2020 due to the stringent public health measures implemented to curb COVID-19 ***,the easing of these restrictions subsequently led to a resurgence in dengue cases,as reported by the World Health Organization,with a notable increase compared to previous *** the country navigates towards a post-pandemic phase,addressing the resurgence of dengue requires sustained efforts in vector control,surveillance,and healthcare *** article underscores the critical need for collab-orative efforts among stakeholders to mitigate the resurgence of dengue while managing the ongoing recovery from the COVID-19 pandemic.

关键词： Dengue Dengue fever COVID-19 Pandemic SARS-CoV-2 Philippines

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深孔金刚石钻进

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国外地质勘探技术 1980年第10期 34-37页

作者： j.savage 张才林

希思·舍伍德钻井公司(Heath & Sherwood Drilling)是在原有公司的基础上于1951年重新组建的。原有限公司从事金刚石钻进和金刚石钻进设备的制造,而新公司则专门从事金刚石钻进。据估计,20多年来加拿大百分之九十的5Q00英尺以下深取心... 详细信息

希思·舍伍德钻井公司(Heath & Sherwood Drilling)是在原有公司的基础上于1951年重新组建的。原有限公司从事金刚石钻进和金刚石钻进设备的制造,而新公司则专门从事金刚石钻进。据估计,20多年来加拿大百分之九十的5Q00英尺以下深取心孔都是由希斯·舍伍德公司承包的。在全加拿大和世界许多国家如智利、巴西、巴基

关键词：金刚石钻进舍伍德希思希斯提引钻机钻井机深孔钻进井架钻塔

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Cognitive changes associated with ADT： a review of the literature

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Asian journal of Andrology 2012年第2期14卷 232-238页

作者： Rhoda j jamadar mary j Winters Pauline M Maki Center for Cognitive Medicine Department of Psychiatry university of Illinois at Chicago Chicago IL 60612 USA Department of Psychology University of Illinois at Chicago Chicago IL 60612 USA

The use of androgen deprivation therapy （ADT） has increased since the early 1990s after early detection efforts and greater use of the prostate-specific antigen （PSA） test. Although ADT is associated with favorable clinical outcomes, ADT has been associated with an increased risk for cardiovascular disease, increased serum cholesterol, triglycerides, insulin resistance, body mass index and fat body mass. Here we review findings from 11 clinical studies examining the effects of ADT on cognition as measured by standardized tests in cognitive domains such as verbal and spatial memory. Most of these studies have important limitations, including small sample sizes, suboptimal control groups and baseline group differences in confounding factors. Despite these limitations, the best designed studies, those comparing patients on ADT to healthy controls, generally suggest that spatial memory might be especially sensitive to the effects of ADT. Critically, to date there is only one study involving random assignment of ADT versus close clinical observation. That study revealed a decrease in verbal memory with ADT, but was limited in sample size and did not include a measure of spatial memory. A recent observational study revealed no substantial evidence of cognitive impairment with ADT, even in the domain of verbal memory. Like the randomizedstudy, however, this large observational study lacked a measure of spatial memory. Overall, the studies with the best controls suggest a potential negative impact of ADT on spatial memory, and perhaps verbal memory, and a need for continued investigation of the impact of ADT on cognition, particularly in these two cognitive domains.

关键词： androgen deprivation therapy cognition prostate cancer

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IgG Fc engineering to modulate antiboc affector functions

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Protein & Cell 2018年第1期9卷 63-73页

作者： Xinhua Wang mary Mathieu Randall j. Brezski Genentech Antibody Engineering South San Francisco CA 94080 USA

Therapeutic monoclonal antibodies are among the most effective biotherapeutics to date. An important aspect of antibodies is their ability to bind antigen while at the same time recruit immune effector functions. The majority of approved recombinant monoclonal antibody therapies are of the human IgG1 subclass, which can engage both humoral and cellular components of the immune system. The wealth of information generated about antibodies has afforded investigators the ability to molecularly engineer antibodies to modulate effector functions. Here, we review various antibody engineering efforts intended to improve efficacy and safety relative to the human IgG isotype. Further, we will discuss pro- posed mechanisms by which engineering approaches led to modified interactions with immune components and provide examples of clinical studies using next generation antibodies.

关键词： antibody-dependent cell-mediated cytotoxicity antibody-dependent cellular phagocytosis,complement-dependent cytotoxicity Fc engineering Fcgamma receptor monoclonal antibody neonatal Fc receptor

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Adding Value to Crop Production Systems by Integrating Forage Cover Crop Grazing

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American journal of Plant Sciences 2024年第3期15卷 180-192页

作者： Robert B. Mitchell Daren D. Redfearn Kenneth P. Vogel Terry j. Klopfenstein Galen Erickson P. Stephen Baenziger Bruce E. Anderson mary E. Drewnoski jay Parsons Steven D. Masterson Marty R. Schmer Virginia L. jin USDA-ARS Wheat Sorghum and Forage Research Unit University of Nebraska-Lincoln Lincoln NE USA Department of Agronomy and Horticulture University of Nebraska-Lincoln Lincoln NE USA Department of Animal Science University of Nebraska-Lincoln Lincoln NE USA Department of Agricultural Economics University of Nebraska-Lincoln Lincoln NE USA USDA-ARS Agroecosystem Management Research Unit University of Nebraska-Lincoln Lincoln NE USA

In addition to their value as cereal grains, wheat (Triticum aestivum L.) and triticale (× Triticosecale Wittmack) are important cool-season annual forages and cover crops. Yearling steer (Bos taurus) performance was compared in the spring following autumn establishment as for age cover crops after soybean [Glycine max (L.) Merr.] grain harvest. Replicated pastures (0.4 ha) were no-till seeded in three consecutive years into soybean stubble in autumn, fertilized, and grazed the following spring near Ithaca, NE, USA. Each pasture (n = 3) was continuously stocked in spring with four yearling steers (380 ± 38 kg) for 17, 32, and 28 d in 2005, 2006, and 2007, respectively. In 2005, average daily gain (ADG) for steers grazing triticale exceeded the ADG for wheat by 0.31 kghd-1d-1. In 2006, wheat ADG exceeded that for triticale by 0.12 kghd-1d-1. In 2007, steers grazing wheat lost weight, while steers grazing triticale gained 0.20 kghd-1d-1. Based on the 3-year average animal gains valued at $1.32 kg-1, mean net return ($ ha-1 yr-1) was $62.15 for triticale and $22.55 for wheat. Since these grazed cover crops provide ecosystem services in addition to forage, grazing could be viewed as a mechanism for recovering costs and adds additional value to the system. Based on this 3-year grazing trial, triticale was superior to wheat and likely will provide the most stable beef yearling performance across years with variable weather for the western Cornbelt USA.

关键词： Cover crops Soybean Triticale Wheat

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Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

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World journal of Gastrointestinal Oncology 2014年第5期6卷 112-120页

作者： Kyle j Napier mary Scheerer Subhasis Misra Department of Surgery Texas Tech University Health Science Center School of Medicine Division of Surgical Oncology Chief of GastroIntestinal and Hepato-Pancreato-Biliary Surgery Texas Tech University Health Science Center School of Medicine

Esophageal cancer is a serious malignancy with regards to mortality and prognosis. It is a growing health concern that is expected to increase in incidence over the next 10 years. Squamous cell carcinoma is the most common histological type of esophageal cancer worldwide, with a higher incidence in developing nations. With the increased prevalence of gastroesophageal reflux disease and obesity in developed nations, the incidence of esophageal adenocarcinoma has dramatically increased in the past 40 years. Esophageal cancer is staged according to the widely accepted TNM system. Staging plays an integral part in guiding stage specific treatment protocols and has a great impact on overall survival. Common imaging modalities used in staging include computed tomography, endoscopic ultrasound and positron emission tomography scans. Current treatment options include multimodality therapy mainstaysof current treatment include surgery, radiation and chemotherapy. Tumor markers of esophageal cancer are an advancing area of research that could potentially lead to earlier diagnosis as well as playing a part in assessing tumor response to therapy.

关键词： Esophageal cancer Esophageal cancer staging Esophageal squamous cell carcinoma Esophageal adenocarcinoma Surgery

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Ground-based and additional science support for SMILE

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Earth and Planetary Physics 2024年第1期8卷 275-298页

作者： j.A.Carter M.Dunlop C.Forsyth K.Oksavik E.Donovon A.Kavanagh S.E.Milan T.Sergienko R.C.Fear D.G.Sibeck M.Connors T.Yeoman X.Tan M.G.G.T.Taylor K.McWilliams j.Gjerloev R.Barnes D.D.Billet G.Chisham A.Dimmock M.P.Freeman D.-S.Han M.D.Hartinger S.-Y.W.Hsieh Z.-j.Hu M.K.james L.juusola K.Kauristie E.A.Kronberg M.Lester j.Manuel j.Matzka I.McCrea Y.Miyoshi j.Rae L.Ren F.Sigernes E.Spanswick K.Sterne A.Steuwer T.Sun M.-T.Walach B.Walsh C.Wang j.Weygand j.Wild j.Yan j.Zhang Q.-H.Zhang Planetary Sciences Group School of Physics and AstronomyUniversity of LeicesterUniversity RoadLeicesterLE17RHUK Rutherford Appleton Laboratory Space Science Technology Facilities CouncilOxfordshireUK School of Space and Environment Beihang UniversityBeijing 100191China Key Laboratory of Space Environment Monitoring and Information Processing Ministry of Industry and Information TechnologyBeijing 100017China Department of Space and Climate Physics UCLMullard Space Science LaboratoryHolmbury St.MaryDorkingSurreyRH56NTUK Birkeland Centre for Space Science Department of Physics and Technology.University of BergenBergenNorway Department of Physics and Astronomy University of Calgary2500 University DriveCalgaryAlbertaCanada T2N 1N4 British Antarctic Survey CambridgeUK Swedish Institute of Space Physics KirunaSweden West Highfield Campus University of SouthamptonUniversity RoadSO171BJUK Goddard Space Flight Center NASAGreenbeltMarylandUSA Athabasca University AthabascaCanada ESTEC European Space AgencyNetherlands University of Saskatchewan SaskatoonCanada The johns Hopkins University Applied Physics Laboratory LaurelMarylandUSA Swedish Institude of Space Physics UppsalaSE 75121Sweden Tongji University Shanghai 200092China Center for Space Plasma Physics Space Science Institute4765 Walnut Street Suite BBoulderColorado80301USA Polar Research Institute of China Shanghai 200136China Finnish Meteorological Institute(FMI) Finland Department of Earth and Environmental Sciences(Geophysics) Ludwig Maximilian University of Munich(LMU)MunichTheresienstr.41MunichD-80333Germany Canadian Space Agency MontrealCanada GFZ German Research Centre for Geosciences PotsdamGermany Nagoya University Institute for Space Earth Environment ResearchCenter for Integrated Data ScienceNagoyaAichiJP 464-8601 Northumbria University Newcastle upon TyneTyne and WearUK NE18ST National Space Science Center Chinese Academy SciencesBeijing 100190China Arctic Geophysics University Centre in Svalbard

The joint European Space Agency and Chinese Academy of Sciences Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)mission will explore global dynamics of the magnetosphere under varying solar wind and interplanetary magnetic field conditions,and simultaneously monitor the auroral response of the Northern Hemisphere *** these large-scale responses with medium and fine-scale measurements at a variety of cadences by additional ground-based and space-based instruments will enable a much greater scientific impact beyond the original goals of the SMILE ***,we describe current community efforts to prepare for SMILE,and the benefits and context various experiments that have explicitly expressed support for SMILE can offer.A dedicated group of international scientists representing many different experiment types and geographical locations,the Ground-based and Additional Science Working Group,is facilitating these *** include constructing an online SMILE Data Fusion Facility,the discussion of particular or special modes for experiments such as coherent and incoherent scatter radar,and the consideration of particular observing strategies and spacecraft *** anticipate growing interest and community engagement with the SMILE mission,and we welcome novel ideas and insights from the solar-terrestrial community.

关键词： magnetosphere ionosphere magnetosphere-ionosphere coupling ground-based experimentation SMILE conjunctions missions

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