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Abrogation of immune complex glomerulonephritis by native carboxypeptidase and pharmacological antagonism of the C5a receptor

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Cellular & Molecular Immunology 2016年第5期13卷 651-657页

作者： jessy j. Alexander lee d. Chaves Anthony Chang Shruti dighe Alexander jacob Richard j. Quigg division of Nephrology Department of Medicine University at Buffalo School of Medicine and Health Sciences Buffalo NY USA department of Pathology The University of Chicago Chicago IL USA Correspondence: Dr Jessy J. Alexander Division of Nephrology State University of New York at Buffalo Clinical and Translational Research Center 875 Ellicott Street 8-022 Buffalo NY 14203 USA

Activation of complement generates C5a which leads to signaling through C5aR 1. This is tightly controlled, including by the plasma proteins factor H （FH） and carboxypeptidase N. Here we studied a chronic serum sickness （CSS） model of glomerulonephritis （GN） in which there is an active humoral immune response, formation of glomerular immune complexes （ICs）, and resulting glomerular inflammation. The antibody response, glomerular IC deposition, the degree of GN, and consequent renal functional insufficiency in CSS were all worse in FH-/- mice compared to wild-type FH＋/＋ animals. This was ameliorated in the former by giving a C5aR1 antagonist for the final 3 weeks of the 5-week protocol. In contrast, blocking CP-mediated inactivation of C5a increased these disease measures. Thus, complement regulation by both plasma FH and CP to limit the quantity of active C5a is important in conditions where the humoral immune response is directed to a continuously present foreign antigen. Signaling through C5aR1 enhances the humoral immune response as well as the inflammatory response to ICs that have formed in glomeruli. Both effects are relevant even after disease has begun. Thus, pharmacological targeting of C5a in IC-mediated GN has potential clinical relevance.

关键词： C5a carboxypeptidase N factor H glomerulonephritis

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Strip Casting of High Performance Structural Alloys

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journal of Rare Earths 2004年第Z2期22卷 78-84页

作者： S S Park j G lee Nack j Kim Center for Advanced Aerospace Materials Pohang University of Science and TechnologyPohang 790-784Korea Center for Advanced Aerospace MaterialsPohang University of Science and TechnologyPohang 790-784Korea Center for Advanced Aerospace MaterialsPohang University of Science and TechnologyPohang 790-784Korea

There exists a great need for the development of high performance alloys due to increasing demands for energy conservation and environmental protection. Application of strip casting shows a strong potential for the improvement of properties of existing alloys and also for the development of novel alloy systems with superior properties. The present paper reviews our Center's activities in the development of high performance alloys by strip casting. Examples include (1) Al alloys, (2) wrought Mg alloys, and (3) bulk metallic glass (BMG) alloys.

关键词： strip casting 6061 Al alloy AZ Mg alloy bulk metallic glass (BMG) alloy dispersion hardening

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Nanoscale resistive switching devices for memory and computing applications

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Nano Research 2020年第5期13卷 1228-1243页

作者： Seung Hwan lee Xiaojian Zhu Wei d.Lu department of Electrical Engineering and Computer Science The University of MichiganAnn ArborMichigan 48109USA

With the slowing down of the Moore’s law and fundamental limitations due to the von-Neumann bottleneck,continued improvements in computing hardware performance become increasingly more *** switching(RS)devices are being extensively studied as promising candidates for next generation memory and computing applications due to their fast switching speed,excellent endurance and retention,and scaling and three-dimensional(3d)stacking *** particular,RS devices offer the potential to natively emulate the functions and structures of synapses and neurons,allowing them to efficiently implement neural networks(NNs)and other in-memory computing systems for data intensive applications such as machine learning *** this review,we will examine the mechanisms of RS effects and discuss recent progresses in the application of RS devices for memory,deep learning accelerator,and more faithful brain-inspired computing *** and possible solutions at the device,algorithm,and system levels will also be discussed.

关键词： resistive switching oxygen vacancy metal cation memory application in-memory computing bio-inspired application

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development of mathematical model with a genetic algorithm for automatic arc welding process

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Acta Metallurgica Sinica(English Letters) 2010年第3期23卷 230-240页

作者： d.T.Thao I.S.Kim j.W.jeong j.H.lee j.Y.Shim H.H.Kim department of Mechanical Engineering Mokpo National University

This paper is to represent new algorithms to predict process parameters on top-bead width in robotic gas metal arc（GMA） welding *** models have been developed：linear, curvilinear and intelligent model based on full factorial design with two *** analysis was employed for optimization of the coefficients of linear and curvilinear models, while genetic algorithm（GA） was utilized to estimate the coefficients of an intelligent *** only the fitting of these models were checked and compared by using a variance test（ANOVA）, but also the prediction on top-bead width using the developed models were carried out based on the additional *** developed models were employed to investigate the characteristic between process parameters and top-bead *** solutions and graphical representation showed that the intelligent model developed can be employed for prediction of bead geometry in GMA welding process.

关键词： Top-bead width Genetic algorithm Multiple regression Robotic arc welding GMA welding

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Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert j.Thomas M.Brandon Westover Can Zhang department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(Ad) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of Ad is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

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NECAB family of neuronal calcium-binding proteins in health and disease

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Neural Regeneration Research 2025年第5期20卷 1236-1243页

作者： diones Bueno Michael K.E.Schafer Sudena Wang Michael j.Schmeisser Axel Methner Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany department of Anesthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of Anatomy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interac

关键词： calcium EF hand mitochondria nervous system signal transduction

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EFFECT OF CARBON ANd BORON ON MICROSTRUCTURE ANd MECHANICAL PROPERTIES OF A SINGLE CRYSTAL SUPERALLOY RR 2072

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Acta Metallurgica Sinica(English Letters) 2005年第1期18卷 33-38页

作者： d.H.Kim d.H.Ye j.H.lee Y.S.Yoo C.Y.jo High Temperature Materials Laboratory Korea Institute of Machinery&Materials 66 SangnamChangwonKyungnam 640-010S.Korea dept.of Metallurgy Changwon National Univerisity 9 SarimChagwonKyungnam 640-773S.Korea

Carbon and boron have been considered to strengthen grain boundaries that might form during single crystal *** this study the effect of boron on solidification behavior and creep properties of the carbon doped single crystal RR 2072 has been *** order to understand solidification behavior with boron addition,the solid/liquid interface morphology and solidification microstructure were examined with solidification *** relationship between mi-crostructural evolution and creep properties of the carbon and boron modified single crystal has been also investigated.

关键词： single crystal superalloy defect tolerance directional solidification creep rupture

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A Study of the Critical Nozzle for Flow Rate Measurement of High-Pressure Hydrogen Gas

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journal of Thermal Science 2007年第1期16卷 28-32页

作者： H.d.Kim j.H.lee K.A.Park T.Setoguchi S.Matsuo School of Mechanical Engineering Andong National University388Songchun-dongAndong 760-749Korea dynamics Group Korea Research Institute of Standards and SciencePO Box 102YusongTaejon 305-606Korea department of Mechanical Enginering.Saga University 1Honjo—machiSaga-shiSaga 840—8502Japan

The mass flow rate measurement using a critical nozzle shows the validity of the inviscid theory, indicating that the discharge coefficient increases and approaches unity as the Reynolds number increases under the ideal gas law However, when the critical nozzle measures the mass flow rate of a real gas such as hydrogen at a pressure of hundreds bar, the discharge coefficient exceeds unity, and the real gas effects should be taken into account. The present study aims at investigating the flow features of the critical nozzle using high-pressured hydrogen gas. The axisymmetric, compressible Navier-Stokes computation is employed to simulate the critical nozzle flow, and a fully implicit finite volume method is used to discretize the governing equation system. The real gas effects are simulated to consider the intermolecular forces, which account for the possibility of liquefying hydrogen gas. The computational results are compared with past experimental data. It has been found that the coefficient of discharge for real gas can be corrected properly below unity adopting the real gas assumption.

关键词： critical nozzle compressible flow hydrogen gas ideal gas law real gas effect

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FATIGUE LIVES FOR INdUCTION HARdENEd SHAFTS MATERIALS ACCORdING TO THE ENVIRONMENTAL TEMPERATURES

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Acta Metallurgica Sinica(English Letters) 2005年第5期18卷 585-593页

作者： d.G. lee K.C. jang j.M. Kuk I.S. Kim Korea Institute of Industrial Technology Gwangju 506-824 Korea dept. of Mechanical Engineering Mokpo National University Mokpo 534-729 Korea

Rotary bending fatigue tests were carried out with two kinds of materials, S43C and S50C, using the front engine and front drive shaft （FF shaft） of vehicle. The specimens were induction hardened about 1.0mm depth from the specimen surface, and the hardness value on the surface was about HRC56-60. The tested environment temperatures were -30, 25 and 80℃ in order to look over effect of the induction hardening and the environmental temperatures on the fatigue characteristics. The fatigue limit of induction hardened specimens increased more about 45% than non-hardened specimens showing that the endurances of S43C and S50C were 98.1 and 107.9MPa in non-hardened samples, 147.1 and 156.9MPa in hardened samplesrespectably. The maximum tensile and compressive stress on the small circular defect was about ＋250 and -450MPa respectively when circular defect is situated on top and bottom. The fatigue life increased 80, 25 and -30℃ in order regardless of hardening. In comparison of the fatigue lives on the basis of tested result at 25℃, the fatigue lives of non-hardened specimens decreased about 35%, but that of hardened specimens decreased about only 5% at 80℃ more than at 25℃. And fatigue life of non-hardened and hardened specimens were about 110% and 120% higher at -30℃ than that of 25℃. Based on the result of stress distribution near the defect, the tensile and compressive stress repeatedly generated by load direction were the largest on the small circular defect due to the stress concentration.

关键词： induction hardening fatigue test front engine and front drive shaft,fatigue crack fatigue life fatigue life ratio

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Exploring effects of property variation on fragmentation of metal rings using a simple model

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defence Technology（防务技术） 2023年第5期23卷 1-7页

作者： j.d.Robson department of Materials The University of ManchesterManchesterM139PLUK

A simple finite element implementation of the Mott model for fragmentation of a thin walled ring has been implemented and used to explore the effect of local variations in fracture strain around the *** model has successfully reproduced the fragment size distributions previously reported,which follow a characteristic“Mott distribution”form,providing sufficient(1000)simulations are *** has been shown that this form is retained even when there are large differences in the random distribution of fracture strains or a different choice of function used to describe the fracture strain *** these cases,the strain rate has a much stronger effect than fracture strain distribution the on the average fragment size and fragment ***,for cases where there are a small number of local defects that strongly reduce the fracture strain at certain locations around the ring,the predicted fragment size distribution develops a bimodal *** is also the case for large but gradual variations in fracture strain with position around the *** results have implications for cases where a small number of large pre-existing defects exist,or processing has led to macrozones in the *** utility of a simple fast running model to study these cases is discussed.

关键词： Fragmentation Mott model Property variation

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