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The p75 neurotrophin receptor:at the crossroad of neural repair and death

Neural Regeneration Research 2015年第5期10卷 721-725页

作者： Rick b.Meeker Kimberly S.williams Department of Neurology University of North Carolina Curriculum in Neurobiology University of North Carolina

The strong repair and pro-survival functions of neurotrophins at their primary receptors, TrkA, Trkb and TrkC, have made them attractive candidates for treatment of nervous system injury and disease. However, difficulties with the clinical implementation of neurotrophin therapies have prompted the search for treatments that are stable, easier to deliver and allow more precise regula- tion of neurotrophin actions. Recently, the p75 neurotrophin receptor （p75wrR） has emerged as a potential target for pharmacological control of neurotrophin activity, supported in part by stud- ies demonstrating 1） regulation of neural plasticity in the mature nervous system, 2） promotion of adult neurogenesis and 3） increased expression in neurons, macrophages, microglia, astro- cytes and/or Schwann cells in response to injury and neurodegenerative diseases. Although the receptor has no intrinsic catalytic activity it interacts with and modulates the function of TrkA, Trkb, and TrkC, as well as sortilin and the Nogo receptor. This provides substantial cellular and molecular diversity for regulation of neuron survival, neurogenesis, immune responses and pro- cesses that support neural function. Upregulation of the p75^NTR under pathological conditions places the receptor in a key position to control numerous processes necessary for nervous system recovery. Support for this possibility has come from recent studies showing that small, non-pep- tide p75^NTR ligands can selectively modify pro-survival and repair functions. While a great deal remains to be discovered about the wide ranging functions of the p75^NTR, studies summarized in this review highlight the immense potential for development of novel neuroprotective and neu- rorestorative therapies.

关键词： injury plasticity neurodegenerative disease brain therapy neuron microglia neuralprogenitor

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ORIGIN OF CARbONATE MATERIALS IN THE NORTHERN bASIN OF LAKE bAIKAL AND ITS RELATIONSHIP TO HOLOCENE PALEOCLIMATE

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Chinese Journal of Oceanology and Limnology 1993年第1期11卷 57-69页

作者：邱林青 F.williams Dept of Geological Sciences University of South Carolina Columbia SC 29208 U.S.A

Fine-grained disseminated carbonate was found in Holocene sediments in a core taken from the northern basin of Lake baikal. The core had two distinct facies. a terrigenous blue-clay overlain by a diatomaceous silt. Oxygen and carbon stable isotope analyses, combined with SEM , X-ray diffraction and .palynology, show that the carbonate in the blue-clay layer is pedogenic in origin, rather than biogenic or authigenic . The S C values in the blue clay suggest that the carbonate is derived from a single source , while the carbonate in the diatom-rich layer might be transported by winds from different sources. On the assumption that the carbonate was formed during the post-glacial age and was transported primarily by river runoff, the 18O isotopic values suggest that the annual temperature in the northern baikal drainage area was about 3℃ warmer during the middle Holocene (8500-7000 a, b. P.) than during the early Holocene (11 000-8 500a, b.P.) when the blue clay was being deposited . This interpretation

关键词： Lake baikal carbonate oxygen isotopes carbon isotopes paleoclimate

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A vaccination model for COVID-19 in Gauteng,South Africa

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Infectious Disease Modelling 2022年第3期7卷 333-345页

作者： Christina J.Edholm benjamin Levy Lee Spence Folashade b.Agusto Faraimunashe Chirove C.williams Chukwu david Goldsman Moatlhodi Kgosimore Innocent Maposa K.A.Jane White Suzanne Lenhart Department of Mathematics Scripps CollegeClaremontCAUSA Mathematics Department Fitchburg State UniversityFitchburgMAUSA Department of Mathematics University of TennesseeKnoxvilleTNUSA Department of Ecology and Evolutionary biology University of KansasLawrenceKSUSA Department of Mathematics and Applied Mathematics University of JohannesburgSouth Africa H.Milton Stewart School of Industrial and Systems Engineering Georgia Institute of TechnologyAtlantaGAUSA biometry and Mathematics Department Botswana University of Agriculture and Natural ResourcesGaboroneBotswana Division of Epidemiology and biostatistics School of Public HealthFaculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa Department of Mathematical Sciences University of BathBathUK

The COVID-19 pandemic provides an opportunity to explore the impact of government mandates on movement restrictions and non-pharmaceutical interventions on a novel infection,and we investigate these strategies in early-stage outbreak *** rate of disease spread in South Africa varied over time as individuals changed behavior in response to the ongoing pandemic and to changing government *** a system of ordinary differential equations,we model the outbreak in the province of Gauteng,assuming that several parameters vary over *** data from the time period before vaccination gives the approximate dates of parameter changes,and those dates are linked to government *** parameters are then estimated from available case data and used to assess the impact of each *** forward in time,possible scenarios give projections involving the implementation of two different vaccines at varying *** results quantify the impact of different government policies and demonstrate how vaccinations can alter infection spread.

关键词： COVID-19 Gauteng South Africa ODE epidemiology Model Vaccination Parameter estimation

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In the presence of danger: the extracellular matrix defensive response to central nervous system injury

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Neural Regeneration Research 2014年第4期9卷 377-384页

作者： Lyn b.Jakeman Kent E.williams bryan brautigam Department of Physiology and Cell biology Ohio State University Wexner Medical CenterColumbusOHUSA Neuroscience Graduate Studies Program Ohio State University Wexner Medical CenterColumbusOHUSA biomedical Research Graduate Program Ohio State University Wexner Medical CenterColumbusOHUSA OSU Center for brain and Spinal Cord Repair Ohio State University Wexner Medical CenterColumbusOHUSA

Glial cells in the central nervous system （CNS） contribute to formation of the extracellular matrix, which provides adhesive sites, signaling molecules, and a diffusion barrier to enhance efficient on and axon potential propagation. In the normal adult CNS, the extracellular matrix （ECM） is relatively stable except in selected regions characterized by dynamic remodeling. However, after trauma such as a spinal cord injury or cortical contusion, the lesion epicenter becomes a focus of acute neuroinflammation. The activation of the surrounding glial cells leads to a dramatic change in the composition of the ECM at the edges of the lesion, creating a perilesion environment dominated by growth inhibitory molecules and restoration of the peripheral/ central nervous system border. An advantage of this response is to limit the invasion of damaging cells and diffusion of toxic molecules into the spared tissue regions, but this occurs at the cost of inhibiting migration of endogenous repair cells and preventing axonal regrowth. The following review was prepared by reading and discussing over 200 research articles in the field published in PubMed and selecting those with significant impact and/or controversial points. This article highlights structural and functional features of the normal adult CNS ECM and then focuses on the reactions of glial cells and changes in the perilesion border that occur following spinal cord or contusive brain injury. Current research strategies directed at modifying the inhibitory perilesion microenvironment without eliminating the protective functions of glial cell activation are discussed.

关键词： nerve regeneration glial scar proteoglycan axon growth spinal cord injury contusion inhibitory inflammation astrocyte macrophage neural regeneration

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冰雹对美国玉米带作物产量影响模拟(英文)

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农业工程学报 2012年第21期28卷 177-185页

作者：王尔大 bertis b.Little Jimmy R.williams 于洋大连理工大学管理学院中国大连116023 美国塔尔顿洲立大学美国德克萨斯州76402 德克萨斯农工大学系统美国德克萨斯州76502 辽宁对外经贸学院金融系中国大连116023

为了尝试计算机模拟方法能否成为制定作物保险保费的辅助性工具,该研究运用计算机模拟模型预测冰雹对作物产量的影响。通过对现有EPIC(综合气候因素的环境政策)模型增加冰雹天气模块,即冰雹事件发生概率的数学模型,模拟冰雹对作物产量... 详细信息

为了尝试计算机模拟方法能否成为制定作物保险保费的辅助性工具,该研究运用计算机模拟模型预测冰雹对作物产量的影响。通过对现有EPIC(综合气候因素的环境政策)模型增加冰雹天气模块,即冰雹事件发生概率的数学模型,模拟冰雹对作物产量的影响。除此之外,该研究还模拟了干旱和霜冻等天气因素对美国Iowa,Illinoi和Indiana等3个玉米带州作物产量的影响。首先介绍数据来源及处理方法,讨论建立冰雹模拟模型过程以及对模型进行有效性检验;然后运用统计分析方法对模型模拟结果与实际观察结果进行比较,检验模型模拟结果的准确性。结果表明EPIC模型可以达到95%甚至更高的产量预测的准确性;同时,冰雹灾害模拟结果也可以达到一个较为合理的准确性(R2>0.7)。这些结果表明本研究所建立的增加冰雹模块的EPIC模型可以作为一个较为可靠的冰雹引起的作物产量损失的预测方法.该模型可以用来模拟冰雹事件发生的概率以及其对各种作物产量造成的损失。

关键词：作物经济分析农业 EPIC 土壤类型冰雹灾害模型模拟

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MEASUREMENT OF SOLID SLURRY FLOW VIA CORRELATION OF ELECTROMAGNETIC FLOW METER,ELECTRICAL RESISTANCE TOMOGRAPHY AND MECHANISTIC MODELLING

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Journal of Hydrodynamics 2009年第4期21卷 557-563页

作者： XU Jing-yu WU Ying-xiang ZHENG Zhi-chu WANG M. MUNIR b. OLUWADAREY H. I. SCHLAbERG H. I. williams R. A. Institute of Mechanics Chinese Academy of Sciences Beijing 100190 China School of Process Environmental and Materials Engineering University of Leeds Leeds UK

The study presented here was carried out to obtain the actual solids flow rate by the combination of electrical resistance tomography and electromagnetic flow meter. A new in-situ measurement method based on measurements of the Electromagnetic Flow Meters （EFM） and Electrical Resistance Tomography （ERT） to study the flow rates of individual phases in a vertical flow was proposed. The study was based on laboratory experiments that were carded out with a 50 mm vertical flow rig for a number of sand concentrations and different mixture velocities. A range of sand slurries with median particle size from 212 μm to 355 μm was tested. The solid concentration by volume covered was 5% and 15%, and the corresponding density of 5% was 1078 kg/m^3 and of 15% was 1238 kg/m^3. The flow velocity was between 1.5 m/s and 3.0 m/s. A total of 6 experimental tests were conducted. The equivalent liquid model was adopted to validate in-situ volumetric solids fraction and calculate the slip velocity. The results show that the ERT technique can be used in conjunction with an electromagnetic flow meter as a way of measurement of slurry flow rate in a vertical pipe flow. However it should be emphasized that the EFM results must be treated with reservation when the flow pattern at the EFM mounting position is a non-homogenous flow. The flow rate obtained by the EFM should be corrected considering the slip velocity and the flow pattern.

关键词： slurry measurement Electrical Resistance Tomography (ERT) Electromagnetic Flow Meters (EFM) in-situ mean volumetric fraction slip velocity

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Numerical investigation of particle saltation in the bed-load regime

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Science China(Technological Sciences) 2014年第8期57卷 1500-1511页

作者： JI ChunNing ANTE Munjiza ELDAD Avital XU Dong JOHN williams State Key Laboratory of Hydraulic Engineering Simulation and Safety Tianjin University School of Engineering & Materials Science Queen MaryUniversity of London

This paper numerically investigates particle saltation in a turbulent channel flow having a rough bed consisting of 2–3 layers of densely packed *** this study,we combined three the state-of-the-art technologies,i.e.,the direct numerical simulation of turbulent flow,the combined finite-discrete element modelling of the deformation,movement and collision of the particles,and the immersed boundary method for the fluid-solid *** we verify our code by comparing the flow and particle statistical features with the published data and then present the hydrodynamic forces acting on a particle together with the particle coordinates and velocities,during a typical *** found strong correlation between the abruptly decreasing particle stream-wise velocity and the increasing vertical velocity at collision,which indicates that the continuous saltation of large grain-size particles is controlled by collision parameters such as particle incident angle,local rough bed packing arrangement,and particle density,*** physical process is different from that of particle entrainment in which turbulence coherence structures play an important *** distribution functions of several important saltation parameters and the relationships between them are *** results show that the saltating particles hitting the windward side of the bed particles are more likely to bounce off the rough bed than those hitting the *** on the above findings,saltation mechanisms of large grain-size particles in turbulent channel flow are presented.

关键词： particle saltation bed-load regime hydrodynamic forces turbulent channel flow

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Genetics of anorexia nervosa:An overview of genome-wide association studies and emerging biological links

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Journal of Genetics and Genomics 2022年第1期49卷 1-12页

作者： Clara de Jorge Martinez Gull Rukh Michael J.williams Santino Gaudio Samantha brooks Helgi bSchi oth Department of Neuroscience Functional PharmacologyUppsala UniversityUppsalaSweden Department of biomedicine and Prevention University of Rome Tor VergataRomeItaly School of Psychology Faculty of HealthLiverpool John Moores UniversityUK Department of Psychology School of Human and Community DevelopmentUniversity of the WitwatersrandJohannesburgSouth Africa Institute for Translational Medicine and biotechnology Sechenov First Moscow State Medical UniversityMoscowRussia

Anorexia nervosa(AN) is a complex disorder with a strong genetic component. Comorbidities are frequent and there is substantial overlap with other disorders. The lack of understanding of the molecular and neuroanatomical causes has made it difficult to develop effective treatments and it is often difficult to treat in clinical practice. Recent advances in genetics have changed our understanding of polygenic diseases,increasing the possibility of understanding better how molecular pathways are intertwined. This review synthetizes the current state of genetic research providing an overview of genome-wide association studies(GWAS) findings in AN as well as overlap with other disorders, traits, pathways, and imaging results. This paper also discusses the different putative global pathways that are contributing to the disease including the evidence for metabolic and psychiatric origin of the disease.

关键词： Anorexia nervosa Genome-wide association studies Genetic variants Psychiatry

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Signalization options to improve capacity and delay at roundabouts through microsimulation approach:A case study on arterial roadways in Ghana

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Journal of Traffic and Transportation Engineering(English Edition) 2021年第1期8卷 70-82页

作者： Kwame Kwakwa Osei Charles Anum Adams williams Ackaah Yolanda Oliver-Commey Regional Transport Research and Education Centre Kumasi(TRECK)Department of Civil EngineeringKwame Nkrumah University of Science and TechnologyKumasiGhana building and Road Research Institute of the Council for Scientific and Industrial Research(CSIR-bRRI) KumasiGhana Pennoni Associates Inc. PhiladelphiaPA 19103USA

Roundabouts are very useful when flows are balanced but can have operational challenges when flows *** roundabouts on arterial roadways in Ghana experience recurring congestion during peak *** four roundabouts between Ejisu Municipality and Asokwa Municipality on the N6 highway are typical of the situation found on arterials *** experience recurring long queues and delays during the peak hours and over-representation of truck rollover *** Ghana,historically,most roundabouts with capacity problems have been developed into interchanges at very high cost without consideration of other effective at-grade *** roundabouts are signalized,various configurations can be explored to enhance capacity while preserving the safety *** simulation techniques,various configurations and design options were tested for their effectiveness at two of the roundabouts,located at KNUST police station and Ejisu,with similar demand and high left turning *** objectives of this study were to a)evaluate the performance of the selected roundabouts on the corridor;b)explore alternative intersection configurations to improve capacity and *** video data collection techniques,2-h time stamped footages of AM and PM peak traffic flows were captured for two *** design parameters of the existing roundabouts,queue lengths,travel times,and approach flows were also *** models of the selected roundabouts were developed and calibrated for the baseline *** unconventional roundabout configuration,with a phase for major road through traffic were simulated and assessed for capacity,delay and queue *** results showed that signalized roundabout intersections effectively increased capacity by as much as 50%in some cases,reduced delay and queue length significantly,and maintained the benefits of roundabouts including *** performance could be further enhanced by introducing separate

关键词： Transportation Signal strategy Roundabout Road safety VISSIM microsimulation Congestion

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Paleoenvironments and geochemistry across a continuous Permian-Triassic boundary section at bukk Mountains,Hungary

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Geoscience Frontiers 2021年第3期12卷 214-233页

作者： M.E.brookfield J.C.williams A.G.Stebbins School for the Environment University of MassachusettsBostonMA 02125USA School of Earth Sciencec The Ohio State UniversityColumbusOH 43210USA

The bálvány North Permian-Triassic boundary sediments were deposited on a carbonate platform in the tropical part of the western Paleo Tethys *** overall elemental geochemistry of the detailed two-metre-thick section across the boundary that we studied shows that the clastic content of the sediments came from dominantly silica-rich continental sources though with some more silica-poor inputs in the uppermost Permian and lowest Triassic limestones as shown by Ni/Al and Nb/Ta *** inputs bracket,but do not coincide with,the main extinctions and associated C,O and S *** aridity at the Permian-Triassic boundary with increased wind abrasion of suitable Ti-bearing heavy minerals accounts for both the high Ti/Al and Ti/Zr *** geochemical redox proxies suggest mainly oxic depositional conditions,with episodes of anoxia,but with little systematic variation across the Permian-Triassic extinction *** lack of consistent element geochemical changes across the Permian-Triassic boundary occur not only in adjacent shallower-water marine sections,and in other marine sections along the SW Tethys margin such as the Salt Range sections in Pakistan,but also in deeper shelf and oceanic sections,and in non-marine African and European continental *** the absence of significant changes in physical environments,chemical changes in the atmosphere and oceans,reflected in various isotopic changes,drove the Permian-Triassic extinctions.

关键词： Permian-Triassic boundary Paleoenvironments geochemistry Hungary bukk

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