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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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Petrologic evolution of the Gysian ophiolitic serpentinites,NW Iran

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Acta Geochimica 2024年第5期43卷 996-1011页

作者： Monir Modjarrad donna l.Whitney Hadi Omrani Department of Geology Faculty of SciencesUrmia UniversityUrmiaIran Department of Earth and Environmental Sciences University of MinnesotaMinneapolisMNUSA Department of Geology Faculty of SciencesGolestan UniversityGorgānIran

The Gysian ophiolite of NW Iran is located at the intersection of the ophiolite belts of SE Turkey,NE Iraq,and Iran,and provides the opportunity to investigate the preserved subduction and obduction history of an important tectonic site that has not previously been *** serpentinized peridotites of the Gysian ophiolite contain the assemblagelizardite+chrysotile+spinel/Mg-spinelwith relict clinopyroxene(diopside)and very rare relict orthopyroxene and *** compositions of clinopyroxenes and spinels are more consistent with the formation of the inferred protolithharzburgitesinafore-arcorsupra-subduction zone instead of an abyssal *** Gysian ophiolite is a remnant of the Neo-Tethyan arc-ophiolitic system and records shallow subduction(late Cretaceous to Paleocene beforeobductionalongthrustfaultsoverthecontinental *** review the spatial trends of the metamorphic grade of the Neo-Tethyan ophiolites in this region and provide detailed information about the petrology and mineral chemistry of the Gysian ophiolite.

关键词： Ophiolite Neo-Tethyan Gysian Serpentinite Iran

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lKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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Genes & Diseases 2024年第3期11卷 417-426页

作者： Zijian Xu Elizabeth R.Davies liudi Yao Yilu Zhou Juanjuan li Aiman Alzetani Ben G.Marshall David Hancock Tim Wallis Julian Downward Rob M.Ewing donna E.Davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely *** previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine ***,we report that liver kinase B1(lKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a *** IPF lungs,this is caused by the down-regulation of CAB39l,a key subunit within the lKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between lKB1-depleted ATIl cells and fibroblasts augmented myofibroblast ***,these data suggest that reduced autophagy caused by lKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39l Crosstalk EMT lKB1 Pulmonary fibrosis

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Neuroimmune actions in the brain and interactions with the effects of alcohol

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Neural Regeneration Research 2021年第9期16卷 1791-1792页

作者： donna l.Gruol Neuroscience Department The Scripps Research InstituteLa JollaCAUSA

The neuroimmune system of the brain:Early studies(1990’s)on the neurological consequences of human immunodeficiency virus-1(HIV-1)infection in the brain were instrumental in establishing that specific brain cell types can function as an innate immune system within the brain and in that role influence cognitive function(Kaul et al.,2005).

关键词： Neuroimmune actions in the brain and interactions with the effects of alcohol

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Preliminary landscape analysis of deep tomographic imaging patents

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Visual Computing for Industry,Biomedicine,and Art 2023年第1期6卷 20-32页

作者： Qingsong Yang donna l.lizotte Wenxiang Cong Ge Wang Rensselaer Polytechnic Institute TroyNY 12180USA Murtha Cullina llP BostonMA 02110USA

Over recent years,the importance of the patent literature has become increasingly more recognized in the aca-demic *** the context of artificial intelligence,deep learning,and data sciences,patents are relevant to not only industry but also academe and other *** this article,we focus on deep tomographic imaging and perform a preliminary landscape analysis of the related patent *** search tool is *** patent biblio-metric data is summarized in various figures and *** particular,we qualitatively analyze key deep tomographic patent literature.

关键词： Artificial intelligence Machine learning Deep learning Medical imaging Tomography Image reconstruction

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High energy femtosecond mid-infrared generation pumped by a two-color Ti:sapphire multipass amplifier

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Chinese Science Bulletin 2008年第5期53卷 664-670页

作者： donna T. Strickland Department of Physics Guelph-Waterloo Physics Institute University of Waterloo 200 University Ave. W. Waterloo Ontario N2L 3G1 Canada

Intense mid-infrared was generated by direct frequency mixing two pulses from a dual-wavelength Ti:sapphire system. From a multipass amplifier we generated two tunable wavelength femtosecond pulses with a total energy of 15 mJ. Pulse energy of 1.6 μJ and 7.4 μJ of mid-infrared light is achieved with and without its multipass amplifier at 9-11 μm, with pulse duration of 500 fs.

关键词：兰宝石激光器红外激光远红外激光超速激光激光放大器

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Much room for optimism on measuring diet, preventing cancer and cardiovascular disease, and correcting for measurement error – discussion of the paper by R. l. Prentice and Y. Huang

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Statistical Theory and Related Fields 2018年第1期2卷 14-20页

作者： donna Spiegelman Harvard T.H.Chan School of Public Health BostonMAUSA

I commend *** and Huang(PH)for their continued and longstanding commitment to the generation of knowledge concerning the nutritional causes of chronic diseases,and in their dedication to applying their extensive,and in the case of ***,virtually unparalleled,expertise towards the development of statistical methods in this regard,to which this paper is one of a long line of such contributions.

关键词： diseases cardiovascular continued

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Wong's nursing care of infants and children / senior consultant, donna l. Wong ; primary author, Marilyn J. Hockenberry ; section editors, David Wilson, Marilyn l. Winkelstein, Nancy E. Kline. 7th ed.

Wong's nursing care of infants and children / senior consult...

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2003年

作者： senior consultant donna l. Wong primary author Marilyn J. Hockenberry section editors David Wilson Marilyn l. Winkelstein Nancy E. Kline.

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Treatment with analgesics after mouse sciatic nerve injury does not alter expression of wound healingassociated genes

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Neural Regeneration Research 2016年第1期11卷 144-149页

作者： Matt C.Danzi Dario Motti donna l.Avison John l.Bixby Vance P.lemmon The Miami Project to Cure Paralysis University of MiamiLois Pope LIFE Center Department of Surgery Leonard M. Miller School of Medicine University of Miami Department of Neurological Surgery University of Miami Department of Molecular and Cellular Pharmacology University of Miami

Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Administration of post-surgical analgesics is an important consideration for animal welfare, but the actions of the analgesic must not interfere with the scientific goals of the experiment. In this study, we show that treatment with either buprenorphine or acetaminophen following a bilateral sciatic nerve crush surgery does not alter the expression in dorsal root ganglion（DRG） sensory neurons of a panel of genes associated with wound healing. These findings indicate that the post-operative use of buprenorphine or acetaminophen at doses commonly suggested by Institutional Animal Care and Use Committees does not change the intrinsic gene expression response of DRG neurons to a sciatic nerve crush injury, for many wound healing-associated genes. Therefore, administration of post-operative analgesics may not confound the results of transcriptomic studies employing this injury model.

关键词： acetaminophen analgesics axon buprenorphine dorsal root ganglia gene expression peripheral nerve injuries regeneration sciatic nerve wound healing

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CourseBuilder for Dreamweaver f/x & design

CourseBuilder for Dreamweaver f/x & design

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2001年

作者： donna l. Baker.

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