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A phase 1b randomized clinical trial of CT1812 to measure Aβoligomer displacement in Alzheimer’s disease using an indwelling CSF catheter

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Translational Neurodegeneration 2023年第1期12卷 568-571页

作者： Kelsie M.LaBarbera Yvette I.Sheline Nicholas j.Izzo Carla M.Yuede Lora Waybright raymond Yurko Hannah M.Edwards Woodrow D.Gardiner Kaj Blennow Henrik Zetterberg Anne Börjesson-Hanson roger Morgan Charles S.Davis robert j.Guttendorf Lon S.Schneider Steven DeKosky Harry LeVine III Michael Grundman Anthony O.Caggiano j.hn r.cirrito Susan M.Catalano Mary E.Hamby Cognition Therapeutics Inc. PittsburghPAUSA University of Pennsylvania PhiladelphiaUSA Washington University St.LouisUSA University of Gothenburg MölndalSweden Department of Psychiatry and Neurochemistry Institute of Neuroscience and PhysiologyThe Sahlgrenska Academy at the University of GothenburgMölndalSweden Clinical Neurochemistry Laboratory Sahlgrenska University HospitalMölndalSweden Department of Neurodegenerative Disease UCL Institute of NeurologyQueen SquareLondonUK UK Dementia research Institute at UCL LondonUK Hong Kong Center for Neurodegenerative Diseases Clear Water BayHong KongChina Wisconsin Alzheimer’s Disease research Center University of Wisconsin School of Medicine and Public HealthUniversity of Wisconsin-MadisonMadisonWIUSA Karolinska University Hospital StockholmSweden MedSurgPI LLCRaleighNCUSA CSD Biostatistics Inc.Oro ValleyAZUSA Aclairo Pharmaceutical Development Group IncViennaVAUSA Keck School of Medicine of USC Los AngelesCAUSA McKnight Brain Institute University of FloridaGainesvilleFLUSA Sanders-Brown Center on Aging University of KentuckyLexingtonKYUSA Global r&D Partners LLCSan DiegoCAUSA Department of Neurosciences University of CaliforniaSan DiegoUSA

Trial registration:May 11th,2018 *** Identifier:NCT03522129 https://clini caltr ***/ct2/show/*** therapies for Alzheimer’s disease(AD)target a wide range of mechanisms,yet promising dis-ease-modifying therapies remain a huge unmet *** evidence indicates that the oligomeric form of amyloid-beta(Aβ)is a toxic species contributing to AD through synaptic damage and neuronal toxicity[1].

关键词： Alzheimer Aβ damage

Compositional complexity dependence of dislocation density and mechanical properties in high entropy alloy systems

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Progress in Natural Science:Materials International 2020年第4期30卷 545-551页

作者： P.Thirathipviwat G.Song j.Bednarcik U.Kühn T.Gemming K.Nielsch j.Han Leibniz Institute of Solid State and Materials research (IFW Dresden) Frontier research Center for Applied Atomic Sciences Ibaraki University Division of Advanced Materials Engineering and Institute for rare metals Kongju National University Institute of Physic Pavol Jozef Safarik University in Ko?ice Deutsches Elektronen-Synchrotron (DESY) Institute of Materials Science Technische Universit?t Dresden Institute of Applied Physics Technische Universit?t Dresden Korea Institute for rare Metals Korea Institute of Industrial Technology (KITECH)

This study focuses on a quantitative analysis of dislocation accumulation after cold plastic deformation and mechanical properties of Fe Ni Co Cr Mn and Ti Nb Hf Ta Zr high entropy alloys(HEAs) which are single phase fcc and bcc solid solutions, respectively. In order to study the role of compositional complexity from unary to quinary compositions on dislocation accumulation and mechanical properties after plastic deformation, the single solid solution phase forming sub-alloys of the two HEAs were investigated. All studied samples revealed a large plastic deformability under cold-rotary swaging process by 85–90% area reduction without intermediate annealing. The dislocation density of all studied samples, determined by Williamson-Hall method on synchrotron X-ray diffraction patterns, were between 1014-1015m-2dependent on the alloy composition. The level of dislocation density after plastic deformation is not only affected by the number of constituent element but the lattice distortion and intrinsic properties in terms of stacking fault energy, modulus misfit, and melting point also impact the dislocation storage. The level of dislocation density determines the level of mechanical properties because of a resistance to dislocation motions. The hardness and yield compressive strength of the studied samples are proportional to the level of dislocation density.

关键词： High entropy alloys Dislocation density Synchrotron XrD Mechanical properties

Laser additive manufactured high-performance Fe-based composites with unique strengthening structure

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journal of Materials Science & Technology 2021年第30期89卷 242-252页

作者： Hongyu Chen Dongdong Gu Liang Deng Tiwen Lu Uta Kühn Konrad Kosiba College of Materials Science and Technology Nanjing University of Aeronautics and AstronauticsNanjing 210016China jiangsu Provincial Engineering Laboratory for Laser Additive Manufacturing of High-Performance Metallic Components Nanjing University of Aeronautics and AstronauticsNanjing 210016China Leibniz IFW Dresden Institute for Complex MaterialsP.O.Box 270116D-01069 DresdenGermany

Steel matrix composites(SMCs),reinforced by ceramic particles,have received a consistent attention in recent *** conventional methods to prepare SMCs is generally challenging,and the mechanical properties of conventionally fabricated SMCs are *** this study,we successfully fabricated highperformance SMCs by laser powder bed fusion(LPBF)of a composite powder consisting of Fe-based alloy powder and submicron-sized WC *** effect of laser energy density on the phase formation,microstructural evolution,overall density and resulting mechanical properties of LPBF-fabricated composites was *** present results show that a novel Fe_(2)W_(4)C carbidic network precipitates in the solidified microstructure entailing segregations along the boundaries of cellular *** presence of this carbidic network hampers the growth of sub-grains even at elevated temperatures,and hence,stabilizes the grain size though prepared at a broad range of different energy *** exact distribution of the Fe_(2)W_(4)C carbides depends on the employed laser energy densities,as for instance they are more uniformly distributed at higher energy *** density of LPBF samples reaches the maximum value of 99.4%at 150 j/mm^(3).In this parameter set,high microhardness of~753 HV,compression strength of~3350 MPa and fracture strain of~24.4%are *** enhanced mechanical properties are ascribed to less metallurgical defects,higher volume fraction of the martensitic phase and increasing pile-up dislocations resulting from the pinning effect by Fe_(2)W_(4)C carbide.

关键词： Laser additive manufacturing Laser powder bed fusion Steel matrix composite Microstructures Mechanical properties

Microstructural Evolution and Mechanical Behaviour of Metastable Cu-Zr-Co Alloys

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journal of Materials Science & Technology 2014年第6期30卷 584-589页

作者： S.Pauly K.Kosiba P.Gargarella B.Escher K.K.Song G.Wang U.Kühn j.Eckert IFW Dresden Institut für Komplexe Materialien HelmholtzstraBe 20D-01069 Dresden Germany Laboratory for Microstructures Shanghai University TU Dresden Institut für WerkstoffwissenschaftD-01062 Dresden Germany

Three different Cu-Zr-Co alloys, namely Cu40Zr37.5Co22.5, Cu42.5Zr45Co12.5 and Cu49Zr49Co2, were obtained by rapid cooling. The microstructure and phase formation of as-cast rods with diameters of 2 mm are compared with those of the respective ingots. An increasing Co content stabilises the B2 CuZr phase and leads to the precipitation of a ternary Cu-Zr-Co phase. The variation of the cooling rate affects the size of the B2 dendrites as well as the volume fraction and the morphology of the interdendritic phases. The mechanical properties were determined in compression and all alloys show a certain plastic deformability despite the presence of several binary and ternary intermetallic phases. The deformation mechanisms are discussed on the basis of the microstructures and the constituent phases.

关键词： Bulk metallic glasses Microstructural evolution Mechanical behaviour

role of the intracellular receptor domain of gp130 (exon 17) in human inflammatory bowel disease

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World journal of Gastroenterology 2005年第8期11卷 1196-1199页

作者： Christoph j.Auernhammer Kathrin Zitzmann Fabian Schnitzler julia Seiderer Peter Lohse George Vlotides Dieter Engelhardt Michael Sackmann Burkhard G(o|¨)ke Thomas Ochsenkühn Department of Internal Medicine Ⅱ-Grosshadern Department of Clinical Chemistry-Grosshadern

AIM: To study the role of the intracellular receptor domain of gp130 in human inflammatory bowel disease (IBD).METHODS: We amplified and sequenced the complete exon 17 of the human gp130 gene in 146 patients with IBD. According to clinical and histopathological signs,the 146 patients with IBD were classified as having Crohn's disease (n = 73) or ulcerative colitis (n = 63),or as indeterminate status (n = 10).rESULTS: No mutations in exon 17 of the gp130 gene could be detected in any of the 146 patients with IBD ***: There is no evidence that mutations in exon 17 of the gp130 gene are involved in the pathogenesis of human IBD.

关键词： Exon 17 Inflammatory bowel disease gp130 gene

No relationship between biopsy sites near the main testicular vessels or rete testis and successful sperm retrieval using conventional or microdissection biopsies in 220 non-obstructive azoospermic men

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Asian journal of Andrology 2013年第6期15卷 795-798,I0009页

作者： j Ullrich Schwarzer Heiko Steinfatt Heiko Steinfatt Manfred Schleyer Frank M Kōhn Klaus Fiedler2, Irene von Hertwig Gottfried Krüsmann Wolfgang Würfel Andrologie Centrum MOnchen MOnchen D-81241 Germany Kinderwunsch Centrum MOnchen MOnchen D-81241 Germany Andrologicum MOnchen MOnchen D-80331 Germany

In 220 consecutive patients with non-obstructive azoospermia, sperm retrieval was attempted by a combination of conventional and microdissection testicular sperm extraction （TESE）. For sperm retrieval, 2-3 conventional biopsies were performed followed by a microdissection TESE in cases of negative conventional biopsies. During the surgery, the vasculature of the testis was assessed using the operative microscope, and the location of positive biopsies was registered in relation to the blood supply. The overall sperm retrieval rate was 58.2%. From the initial conventional biopsies, sperm could be retrieved in 46.8% of the patients. With microdissection TESE, sperm could be retrieved from an additional 11.4% of the patients. The further use of microdissection TESE improved the sperm retrieval rate significantly （P=0.017）. No significant accumulation of positive biopsies was found towards the rete testis or the main testicular vessels.

关键词： intracytoplasmic sperm injection male infertility microdissection testicular sperm extraction non-obstructiveazoospermia sperm retrieval

Phase formation of a biocompatible Ti-based alloy under kinetic constraints studied via in-situ high-energy X-ray diffraction

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Progress in Natural Science:Materials International 2020年第3期30卷 432-436页

作者： Konrad Kosiba André rothkirch junhee Han Liang Deng Benjamin Escher Gang Wang Uta Kühn jozef Bednarcik Leibniz IFW Dresden Institute for Complex Materials DESY Photon Science 3. Korea Institute of Industrial Technology (KITECH) Korea Institute for Rare Metals 4. Fraunhofer Institute for Photonic Microsystems IPMS Department of Engineering 5. Laboratory for Microstructures Institute of Materials Shanghai University 6. J. Safarik University in Kosice Institute of Physics Department of Condensed Matter Physics

The biocompatible Ti40Cu34Pd14Zr10Sn2bulk metallic glass was rapidly heated,also known as flash-annealed,at varying heating rates up to 1579 K/***,the phase formation was characterized via advanced in-situ highenergy X-ray *** has been found that the evolving kinetic constraints can be used as a tool to deliberately alter the crystalline phase *** novel processing route permits to select phases to crystallize to a predefined fraction and,thus,to potentially design the microstructure of materials according to a specified ***,flash-annealing poses a unique synthesis route to design materials with,for instance,good biomechanical compatibility.

关键词： High-energy X-ray diffraction Flash-annealing Phase formation Metallic glass Biocompatible Ti alloy

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接触斑点对蜗轮副承载能力的影响

机械传动 2014年第10期38卷 9-13,17页

作者： Hermes j. Hhn B.-r. Stahl K. Monz A. 陈金山 SEW-Eurodrive传动设备德国有限公司德国布鲁克塞尔76646 慕尼黑工业大学齿轮研究中心(FZG) 德国加兴85748 德国IMO集团公司德国格蕾姆斯多夫91350 浙江台玖精密机械有限公司浙江嘉兴314500

根据现有的技术发展水平,只有当蜗轮副的齿面完全啮合,才能评估其抗点蚀能力。但实际上,在蜗轮与蜗杆初始啮合时,它们只有一个较小的啮合斑点。由于时间和经费的关系,通过长时间轻载跑合使其达到完全啮合一般不太可能。在初期,由于接触... 详细信息

根据现有的技术发展水平,只有当蜗轮副的齿面完全啮合,才能评估其抗点蚀能力。但实际上,在蜗轮与蜗杆初始啮合时,它们只有一个较小的啮合斑点。由于时间和经费的关系,通过长时间轻载跑合使其达到完全啮合一般不太可能。在初期,由于接触面较小,齿部的接触应力会很大,有可能会在啮合处的表面产生一条微观裂纹,随后裂纹继续发展使材料从蜗轮上剥落,从而形成点蚀。较小的啮合斑点与点蚀的关系迄今还没有被系统的分析与研究,因此蜗轮轮齿也不能很好的进行优化。通过理论和实践相结合,提一种新的、可适用于不同尺寸、不同接触斑点位置以及齿形的计算方法,以弥补这一空白领域。

关键词：蜗轮蜗杆点蚀

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GLOBAL ASYMPTOTIC STABILITY IN N-SPECIES NONAUTONOMOUS LOTKA-VOLTErrACOMPETITIVE SYSTEMS WITH DELAYS

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Acta Mathematica Scientia 2003年第2期23卷 208-218页

作者：徐瑞陈兰荪 M.A.j.Chaplain Department of Mathematics Mechanical Engineering College Institute of Mathematics Academia Sinica Department of Mathematics University of Dundee

A delayed n-species nonautonomous Lotka-Volterra type competitive system without dominating instantaneous negative feedback is investigated. By means of a suitable Lyapunov functional, sufficient conditions are derived for the global asymptotic stability of the positive solutions of the system. As a corollary, it is shown that the global asymptotic stability of the positive solution is maintained provided that the delayed negative feedbacks dominate other interspecific interaction effects with delays and the delays are sufficiently small.

关键词： Nonautonomous Lotka-Volterra competitive system finite and infinite delay global asymptotic stability Lyapunov functional