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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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Spatial targeting evaluation of energy and environmental performance of waste-to-energy processing

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Frontiers of Chemical Science and Engineering 2018年第4期12卷 731-744页

作者： Petar S.Varbanov Timothy G.Walmsley Yee V.Fan jiri j.Klemes simon j.Perry Sustainable Process Integration Laboratory NETME CentreFaculty of Mechanical EngineeringBmo University of Technology61669 Bmo Czech Republic Centre for Process Integration School of Chemical Engineering and Analytical ScienceThe University of ManchesterManchester M I 3ALUK

Waste-to-energy supply chains are important potential contributors to minimising the environmental impacts of municipal solid waste by reducing the amounts of waste sent to landfill, as well as the fossil fuel consumption and environmental footprints. Accounting for the spatial and transport properties of the waste-to-energy supply chains is crucial for understanding the problem and improving the supply chain designs. The most significant challenge is the distributed nature of the waste generation and the household energy demands. The current work proposes concepts and a procedure for targeting the size of the municipal solid waste collection zone as the first step in the waste-to-energy supply chains synthesis. The formulated concepts and the provided case study reveal trends of reducing the net greenhouse gas savings and energy recovery by increasing the collection zone size. Population density has a positive correlation with the greenhouse gas saving and energy recovery performance. For smaller zone size the energy recovery from waste approaches and in some cases may surpass the energy spent on waste transportation. The energy recovery and greenhouse gas savings remain significant even for collection zones as large as 200 km2. The obtained trends are discussed and key directions for future work are proposed.

关键词： waste-to-energy supply chain optimisation GHG savings energy recovery ratio

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Taking FAIR on the ChIN:The Chemistry Implementation Network

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Data Intelligence 2020年第1期2卷 131-138,310页

作者： simon j.Coles jeremy G.Frey Egon L.Willighagen Stuart j.Chalk School of Chemistry Faculty of Engineering and Physical SciencesUniversity of SouthamptonSouthampton SO171BJUK Department of Bioinformatics Maastricht UniversityMaastrichtLimburg 6200 MDThe Netherlands Department of Chemistry University of North FloridaJacksonvilleFL 32224-7699USA

The Chemistry Implementation Network(ChIN)is focused on supporting the FAIR Data needs of the research community regarding chemical related *** Implementation Network is a consortium drawn from a community,in this case the chemistry discipline,committed to defining and constructing standards,materials and software in the spirit of the FAIR data principles and under the structure of the GO FAIR ***,as a core science the ChIN has to reach beyond the chemistry community and support the use of chemical information in other *** will be facilitated through connections in the GO FAIR ecosystem of Implementation *** of the FAIR chemical concepts that need to be supported include molecular and materials structures,chemical reactions,nomenclature and other chemical terminology and *** ChIN aims to drive forward the application of the FAIR Data Principles relating to the full range of chemistry concepts that are key to the transparent and efficient communication of chemical *** the goal of FAIR chemistry data will require a culture change across the *** this is best addressed once a critical mass of tools and approaches has been developed.

关键词： Chemistry Chemical information Chemistry data Chemical data standards Infrastructure Nomenclature Molecular structure Materials structure Chemical reactions Education Community engagement Endorsement and governance

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Factor analysis identifies subgroups of constipation

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World journal of Gastroenterology 2011年第11期17卷 1468-1474页

作者： Philip G Dinning Mike jones Linda Hunt Sergio E Fuentealba jamshid Kalanter Denis W King David Z Lubowski Nicholas j Talley Ian j.cook Department of Gastroenterology St.George HospitalUniversity of New South WalesKogarahNSW 2217Australia Department of Psychology Macquarie UniversityNSW 2109Australia Gastroenterology Research Unit Nepean HospitalUniversity of SydneySydneyNSW 2050Australia Department of Colorecta Surgery St.George HospitalKogarahNSW 2217Australia Gastroenterology and Hepatology Mayo ClinicJacksonvilleFL 32224United States

AIM:To determine whether distinct symptom groupings exist in a constipated population and whether such grouping might correlate with quantifiable pathophysiological measures of colonic ***:One hundred and ninety-one patients presenting to a Gastroenterology clinic with constipation and 32 constipated patients responding to a newspaper advertisement completed a 53-item,wide-ranging selfreport *** hundred of these patients had colonic transit measured *** analysis determined whether constipation-related symptoms grouped into distinct aspects of *** analysis was used to determine whether indi-vidual patients naturally group into distinct ***:Cluster analysis yielded a 4 cluster solution with the presence or absence of pain and laxative unresponsiveness providing the main *** all clusters there was a considerable proportion of patients with demonstrable delayed colon transit,irritable bowel syndrome positive criteria and regular stool *** majority of patients with these characteristics also reported regular laxative ***:Factor analysis identified four constipation subgroups,based on severity and laxative unresponsiveness,in a constipated ***,clear stratification into clinically identifiable groups remains imprecise.

关键词： Factor analysis Constipation Symptoms Clusters Laxatives

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Progress in research on Chinese urbanization

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Frontiers of Architectural Research 2012年第2期1卷 101-149页

作者： Chaolin GU Liya WU lan cook School of Architecture Tsinghua UniversityBeijing 100084China School of Politics and Public Administration Suzhou UniversitySuzhou 215006China School of Social Science Liverpool John Moores UniversityLiverpool L32A JUK

This paper is a comprehensive study on the progress in research on Chinese urbanization. On the basis of the concept and connotation of Chinese urbanization defined by Chinese scholars, the paper systematically collects the research results on the issues concerning urbanization in China from the different approaches of demography, geography, city planning, economics and history, reviewin~ the process of research on Chinese urbanization made both domestically and internationally. In this paper, the domestic studies fail into five periods as follows： the initial period of research on urbanization in China （1978-1983）; the period with both domesticaUy constructed and borrowed theories on urbanization （1984-1988）; the period of research on leading urbanization factors and [oca｜ization （1989-1997）; the period with the research greatty promoted by the government （1998-2004）; and the period featuring flourishing studies on the science of urbanization in China （2005 ti[[ today）. In contrast, the overseas research on Chinese urbanization can be divided into three periods： the period studying the history of urbanization in China （before the 1970s）; the systematic research on Chinese urbanization （1970-1999）; and the comprehensive research on Chinese urbanization （2000 tiU today）. The paper focuses on the key results of research on Chinese urbanization, including nine issues as foLLows： the guidelines and road for urban development in China, the features of Chinese urbanization, the mechanism driving the growth of Chinese urbanization, the process of Chinese urbanization, the spatiat patterns of Chinese urbanization, the urbanization in rural areas in China, the comparison of urbanization in China and other countries, and gLobaLization and regional urbanization.

关键词： Urbanization China Policy Urban study Progress

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Capacitance,charge dynamics,and electrolyte-surface interactions in functionalized carbide-derived carbon electrodes

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Progress in Natural Science:Materials International 2015年第6期25卷 631-641页

作者： Boris Dyatkin Eugene Mamontov Kevin M.cook Yury Gogotsi Department of Materials Science & Engineering and A.j.Drexel Nanomaterials Institute Drexel University Spallation Neutron Source Oak Ridge National Laboratory Materials Engineering Division Naval Air Systems Command

This study analyzed the dynamics of ionic liquid electrolyte inside of defunctionalized,hydrogenated,and aminated pores of carbide-derived carbon supercapacitor *** approach tailors surface functionalities and tunes nanoporous structures to decouple the influence of pore wall composition on capacitance,ionic resistance,and long-term ***-elastic neutron scattering probes the self-diffusion properties and electrode-ion interactions of electrolyte molecules confined in functionalized ***-temperature ionic liquid interactions in confined pores are strongest when the hydrogen-containing groups are present on the *** property translates into higher capacitance and greater ion transport through pores during electrochemical *** hydrogenated pores,aminated pores do not favorably interact with ionic liquid ions and,subsequently,are outperformed by defunctionalized surfaces.

关键词： Supercapacitor Carbide-derived carbon Neutron scattering Energy storage Porous materials Surface chemistry

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A primitive mantle source for the Neoarchean mafic rocks from the Tanzania Craton

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Geoscience Frontiers 2016年第6期7卷 911-926页

作者： Y.A.cook I.V.Sanislav j.Hammerli T.G.Blenkinsop P.H.G.M.Dirks Economic Geology Research Centre(EGRU)and Department of Earth and Oceans James Cook UniversityTownsville4011OLDAustralia School of Earth&Ocean Sciences Cardiff UniversityCardiff CF10 3ATUnited Kingdom

Mafic rocks comprising tholeiitic pillow basalt, dolerite and minor gabbro form the basal stratigraphic unit in the ca. 2.8 to 2.6 Ga Geita Greenstone Belt situated in the NW Tanzania Craton. They outcrop mainly along the southern margin of the belt, and are at least 50 million years older than the supracrustal assemblages against which they have been juxtaposed. Geochemical analyses indicate that parts of the assemblage approach high Mg-tholeiite （more than 8 wt.% MgO）. This suite of samples has a restricted compositional range suggesting derivation from a chemically homogenous reservoir. Trace element modeling suggests that the mafic rocks were derived by partial melting within the spinel peridotite field from a source rock with a primitive mantle composition. That is, trace elements maintain primitive mantle ratios （Zr/Hf = 32-35, Ti/Zr - 107-147）, producing flat REE and HFSE profles [（La/Yb）pm = 0.9 -1.3], with abundances of 3-10 times primitive mantle and with minor negative anomalies of Nb [（Nb/ La）pm - 0.6-0.8] and Th [（Th/La）pm = 0.6-0.9]. Initial isotope compositions （εNd） range from 1.6 to 2.9 at 2.8 Ga and plot below the depleted mantle line suggesting derivation from a more enriched source compared to present day MORB mantle. The trace element composition and Nd isotopic ratios are similar to the mafic rocks outcropping -50 km south. The mafic rocks outcropping in the Geita area were erupted through oceanic crust over a short time period, between -2830 and-2820 Ma; are compositionally homogenous, contain little to no associated terrigenous sediments, and their trace element composition and short emplacement time resemble oceanic plateau basalts. They have been interpreted to be derived from a plume head with a primitive mantle composition.

关键词： Mafic rocks Archean Tanzania Craton Primitive mantle MORB Oceanic plateau

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Early Identification of Stable Transformation Events by Combined Use of Antibiotic Selection and Vital Detection of Green Fluorescent Protein (GFP) in Carrot (Daucus carota L.) Callus

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Agricultural Sciences in China 2008年第6期7卷 664-671页

作者： Yuan-Yeu Yau Seth j Davis Ahmet Ipek Philipp W simon U.S. Department of Agriculture Agricultural Research Service Department of Horticulture University of Wisconsin-Madison Laboratory of Genetics University of Wisconsin-Madison Madison WI 53706 USA U.S. Department of Agriculture Agricultural Research Service Department of Horticulture University of Wisconsin-Madison Madison WI 53706 USA

Genetic transformation is a useful technique to complement conventional breeding in crop improvement. Although carrot has been a model organism for in vitro embryogenesis study, genetic transformation of carrot is still lengthy and labor intensive. An efficient transformation and detection system is desirable. Direct infection of Agrobacterium to carrot calli has provided an easy way for carrot genetic transformation. To improve the efficiency of antibiotic selection in this method, we report the combined use of an improved green-fluorescent protein, referred to as smGFP, to establish a versatile selection method for carrot callus transformation system. By combining antibiotic selection with the bright fluorescence observed in the callus tissue, we were able to easily identify stable transformants in early stage of the transformation process. In addition to the GFP expression of the callus cells, the transgenic nature of callus cells was confirmed with Southern and Western analysis. We found we can link the simplicity of carrot-callus-cell transformation, early detection of stable transformants with antibiotic selection, visualization of GFP fluorescence, and molecular analysis （Southern and Western） of callus tissue （non-photosynthetic tissue） to provide a more efficient way in identifying stable transformants at early stage of carrot transformation.

关键词： Agrobacterium tumefaciens antibiotic selection Daucus carota genetic transformation reporter gene,stable transformed transgene

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The complexity of sediment recycling as revealed by common Pb isotopes in K-feldspar

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Geoscience Frontiers 2018年第5期9卷 1515-1527页

作者： simon P.johnson Christopher L.Kirkland Noreen j.Evans Brad j.McDonald Huntly N.Cutten Geological Survey of Western Australia Mineral House100 Plain StreetEast PerthWestern Australia6004Australia Centre for Exploration Targeting-Curtin Node The Institute for Geoscience ResearchDepartment of Applied GeologyWestern Australian School of MinesCurtin UniversityPerthWestern Australia6102Australia john de Laeter Centre The Institute for Geoscience ResearchDepartment of Applied Geology and Applied PhysicsCurtin UniversityPerthWestern Australia6102Australia

Detrital zircon U-Pb geochronology has become the gold standard in evaluating source to sink relationships in sedimentary basins. However, the physical and chemical robustness of zircon, which make it such a useful mineral for provenance studies, is also a hindrance as zircon can be recycled through numerous sedimentary basins, thus obscuring the first cycle source to sink relationship. An elegant approach to addressing this potential issue is to compare the Pb isotope composition of detrital K-feldspar, a mineral which is unlikely to survive more than one erosion-transport-deposition cycle, with that of magmatic K-feldspar from potential basement source terranes. Here we present new in situ Pb isotope data on detrital K-feldspar from two Proterozoic arkosic sandstones from Western Australia, and magmatic K-feldspar grains from potential igneous source rocks, as inferred by the age and Hf isotope composition of detrital zircon grains. The data indicate that the detrital zircon and K-feldspar grains could not have been liberated from the same source rocks, and that the zircon has most likely been recycled through older sedimentary basins. These results provide a more complete understanding of apparently simple source to sink relationships in this part of Proterozoic Western Australia.

关键词： Detrital zircon K-feldspar Pb isotopes Sediment provenance Sediment recycling

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Oil-bearing fluid inclusions from the Palaeoproterozoic:A review of biogeochemical results from time-capsules >2.0 Ga old

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Science China Earth Sciences 2009年第1期52卷 1-11页

作者： simon C. GEORGE Adriana DUTKIEWICZ Herbert VOLK john RIDLEY David j. MOSSMAN Roger BUICK Department of Earth and Planetary Sciences Macquarie University School of Geosciences University of Sydney CSIRO Petroleum Department of Geosciences Colorado State University Department of Geography Mount Allison University Department of Earth and Space Sciences & Astrobiology Program University of Washington

The observation of oil inclusions trapped prior to 2.0 Ga in Palaeoproterozoic rocks and the ability to obtain detailed molecular geochemical information from them provide a robust way for understanding the early biog... 详细信息

关键词： Palaeoproterozoic fluid inclusion oil biomarker blank

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