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High affinity soluble ILT2 receptor:a potent inhibitor of CD8^(+)T cell activation

Protein & Cell 2010年第12期1卷 1118-1127页

作者： Ruth K.Moysey Yi Li Samantha J.Paston Emma E.Baston Malkit S.Sami Brian J.Cameron Jessie Gavarret Penio Todorov Annelise Vuidepot Steven M.Dunn Nicholas J.Pumphrey Katherine J.Adams Fang Yuan Rebecca E.Dennis Deborah H.Sutton Andy D.Johnson Joanna E.Brewer Rebecca Ashfield Nikolai M.Lissin Bent K.Jakobsen Immunocore Limited 57c Milton ParkAbingdonOxonOX144RXUK current address:Oxford Nanopore Technologies UK current address:Geneva Merck Serono S.A. Switzerland current address:Adaptimmune Limited UK

Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin superfamily receptor ILT2(synonyms:LIR1,MIR7,CD85j),we have selected a range of mutants with binding affinities enhanced by up to 168,000-fold towards the conserved region of major histocompatibility complex(MHC)class I *** in a dimeric form,either by chemical cross-linking with bivalent polyethylene glycol(PEG)derivatives or as a genetic fusion with human IgG Fc-fragment,the mutants exhibited a further increase in ligand-binding strength due to the avidity effect,with resident half-times(t1/2)on the surface of MHC I-positive cells of many *** novel compounds antagonized the interaction of CD8 co-receptor with MHC I in vitro without affecting the peptide-specific binding of T-cell receptors(TCRs).In both cytokine-release assays and cell-killing experiments the engineered receptors inhibited the activation of CD8^(+)cytotoxic T lymphocytes(CTLs)in the presence of their target cells,with subnanomolar potency and in a dose-dependent *** a selective inhibitor of CD8^(+)CTL responses,the engineered high affinity ILT2 receptor presents a new tool for studying the activation mechanism of different subsets of CTLs and could have potential for the development of novel autoimmunity therapies.

关键词： CD8^(+)T cells cellular activation autoimmunity cell surface molecules binding affinity phage display

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NAVIER-STOKES ANALYSIS OF A CIRCULATION CONTROL AIRFOIL

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Acta Mechanica Sinica 1995年第2期11卷 137-143页

作者：刘晶昌孙茂吴礼义 current address is Institute of Engineering Thermophysics Chinese Acadamy of Sciences Beijing China 100080 Beijing University of Aeronautics and Astronautics Beijing China 100083

The two-dimensional, compressible, mass-averaged Navier-Stokes equations are used to investigate hows about a typical circulation control airfoil. The governing equations are solved using the implicit approximate-factorization algorithm of Beam-Warming with a modified algebraic eddy viscosity model. Results are compared with experimental data, and excellent agreement is obtained. The effects of different jet momentum coefficients and angles of attack on the how are studied. The mechanism of genenating large lift by circulation control is discussed.

关键词： CIRCULATION CONTROL AIRFOIL NAVIER-STOKES EQUATIONS

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CRACK DETECTION OF STRUCTURE FOR PLANE PROBLEM WITH SPATIAL WAVELETS

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Acta Mechanica Sinica 1999年第1期15卷 39-51页

作者：王泉王大钧苏先樾 current address:Dept.Mechanical Engin. University of South CarolinaUSA Department of Mechanics Peking UniversityBeijing 100871China

The structure damage detection with spatial wavelets was approached. First, a plane stress problem, a rectangular plate containing a short crack under a distributed loading on the edge, was investigated. The displacement response data along the parallel and perpendicular lines at different positions from the crack were analyzed with the Haar wavelet. The peak in the spatial variations of the wavelets indicates the direction of the crack. In addition, a transverse crack in a cantilever beam was also investigated in the same ways. For these problems, the different crack positions were also simulated to testify the effectiveness of the technique. All the above numerical simulations were processed by the finite element analysis code, ABACUS. The results show that the spatial wavelet is a powerful tool for damage detection, and this new technique sees wide application fields with broad prospects. (Edited author abstract) 14 Refs.

关键词： damage detection wavelet transform plane problem

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IL-17C is required for lethal inflammation during systemic fungal infection

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Cellular & Molecular Immunology 2016年第4期13卷 474-483页

作者： Jinling Huang Shaoshuai Meng Shanjuan Hong Xin Lin Wei Jin Chen Dong Institute for Immunology Tsinghua University Beijing 100084 China current address: School of Life Sciences Peking University Beijing 100871 China

Within the interleukin-17 （IL-17） family of cytokines, IL-17A is known to be critical in the host defense against fungal infections; however, the function of the other IL-17 family members in anti-fungal immunity remains largely unknown. Here, we show that IL-17C expression was highly induced in kidney epithelial cells after fungal infection. Mice that lacked IL-17C exhibited increased survival and attenuated kidney tissue damage, although they had similar fungal loads. IL-17C deficiency resulted in decreased pro-inflammatory cytokine expression compared with wild-type control mice. Additionally, IL-17C directly acted on renal epithelial cells in vitro to promote pro-inflammatory cytokine production. Taken together, our data demonstrate that IL-17C is a critical factor that potentiates inflammatory responses and causes host injury during fungal infection.

关键词： fungal infection IL-17C kidney injury pro-inflammatory cytokine sepsis

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Extended finite element methods for optimal control problems governed by Poisson equation in non-convex domains

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Science China Mathematics 2021年第8期64卷 1917-1934页

作者： Tao Wang Chaochao Yang Xiaoping Xie School of Mathematics Sichuan UniversityChengdu 610064China current address:School of Science Chongqing University of TechnologyChongqing 400054China

This paper analyzes two extended finite element methods(XFEMs)for linear quadratic optimal control problems governed by Poisson equation in non-convex *** follow the variational discretization concept to discretize the continuous problems,and apply an XFEM with a cut-off function and a classic XFEM with a fixed enrichment area to discretize the state and co-state *** error estimates are derived for the state,co-state and *** results confirm our theoretical results.

关键词： extended finite element method optimal control non-convex domain variational discretization concept

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Absence of interleukin-1 receptor 1 increases excitatory and inhibitory scaffolding protein expression and microglial activation in the adult mouse hippocampus

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Cellular & Molecular Immunology 2015年第5期12卷 645-647页

作者： Una Avdic Deepti Chugh Harer Osman Katie Chapman Johanna Jackson Christine T Ekdahl Inflammation and Stem Cell Therapy Group Division of Clinical Neurophysiology Lund University Lund Sweden Lund Epilepsy Center Lund University Lund Sweden current address: Division of Neurology Department of Clinical Sciences Lund University Lund Sweden current address: Lilly UK Windlesham Surrey UK

In the present study, we demonstrate that adult mice lacking interleukin- 1 receptor 1 （IL- 1R1） exhibit increased express- ion of both the excitatory scaffolding protein postsynaptic density-95 （PSD-95） and inhibitory scaffolding proteinge- phyrin, respectively, in the hippocampus. The morphology of hippocampal microglia is also altered towards a more activated phenotype. These results indicate an important role for IL-1 signaling in maintaining physiological conditions in both neurons and microglia.

关键词： increases excitatory inhibitory scaffolding

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Photophysical properties of heteroaromatic ring-fused(di)benzosiloles

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Science China Chemistry 2011年第12期54卷 1937-1947页

作者： SHIMIZU Masaki MOCHIDA Kenji KATOH Masaki HIYAMA Tamejiro Department of Material Chemistry Graduate School of EngineeringKyoto University Kyoto University Katsura current address:Research & Development Initiative Chuo University

Benzosiloles fused to heterocycles such as thiophene, benzothiophene, and benzofuran, and indole- and benzosilole-fused dibenzosiloles were prepared by palladium-catalyzed intramolecular coupling of the corresponding 2-（arylsilyl）aryl triflates in good to high yields. Molecular and crystal structures of 5,7-dihydro-5,5,7,7-tetrakis（1-methylethyl）bis[1]benzosilolo-[2,3-b：3＇, 2＇-d]thiophene, 6-methyl-12,12-diisopropyl-12H-indololo[3,2-b][1]silafluorene, and 5,5,11,11-tetraisopropyl-5,11H-benzosilolo[3,2-c]silafluorene were determined by X-ray diffraction analysis. The UV absorption spectra of the （di）benzosilole derivafives in cyclohexane red-shifted when compared to 1,1-diisopropyldibenzosilole, indicating that replacing a benzene ring of dibenzosilole by the heterocycles as well as fusion of indole and benzosilole moieties onto dibenzosilole narrowed the HOMO- LUMO gaps of the n-conjugation system. The thiophene-fused benzosiloles were faintly fluorescent in solution and in the solid state, whereas the dibenzosiloles exhibited luminescence with moderate and high quantum yields in cyclohexane and in microcrystals, respectively. In other words, aggregation-induced emission was observed for the dibenzosiloles. Notably, 5,5,11,1 1- tetraisopropyl-5,11H-benzosilolo[3,2-c]silafluorene in microcrystals exhibited violet fluorescence （λmax = 396 nm） with a quantum yield of 0.70. Density functional theory （DFT） calculations of the prepared （di）benzosiloles were also performed.

关键词： absorption benzosflole fluorescence silicon solid-state emission

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Twenty years hunting for sulfur in DNA

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Protein & Cell 2010年第1期1卷 14-21页

作者： Shi Chen Lianrong Wang Zixin Deng Laboratory of Microbial Metabolism and School of Life Sciences&BiotechnologyShanghai Jiao Tong UniversityShanghai 200030China current address:Department of Cell Biology Harvard Medical SchoolHarvard UniversityBostonMA 02115USA current address:Department of Biological Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA

Here we tell a 20-year long *** began with an easily overlooked DNA degradation(Dnd)phenomenon during electrophoresis and eventually led to the discovery of an unprecedented DNA sulfur modification governed by five dnd *** unusual DNA modification,called phosphorothioation,is the first physiological modification identified on the DNA backbone,in which the nonbridging oxygen is replaced by sulfur in a sequence selective and stereo-specific *** dnd gene clusters have been identified in diverse and distantly related bacteria and thus have drawn immediate attention of the entire microbial scientific ***,we summarize the progress in chemical,genetic,enzymatic,bioinformatical and analytical aspects of this novel postreplicative DNA *** also discuss perspectives on the physiological functions of the DNA phosphorothioate modification in bacteria and their implications.

关键词： DNA sulfur modification DNA phosphorothioate modification DNA degradation

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Mutation of a Gene in the Fungus Leptosphaeria maculans Allows Increased Frequency of Penetration of Stomatal Apertures of Arabidopsis thaliana

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Molecular Plant 2008年第3期1卷 471-481页

作者： Candace E. Elliott Harjono Barbara J. Howletta School of Botany The University of Melbourne Melbourne Vic 3010 Australia . current address: Laboratory of Forest Protection Faculty of Forestry Gadjah Mada University Yogyakarta Indonesia 55281

Leptosphaeria maculans, a pathogen of Brassica napus, is unable to invade most wild-type accessions of Arabidopsis thaliana, although several mutants are susceptible. The infection pathway of L. maculans via a non-invasive inoculation method on A. thaliana Imsl （undefined）, pmr4-1 （defective in callose deposition）, and pen1-1 and pen2-1 （defective in non-host responses to several pathogens） mutants is described. On wild types Col-0 and Ler-0, hyphae are generally arrested at stomatal apertures. A T-DNA insertional mutant of L. maculans （A22） that penetrates stomatal apertures of Col-0 and Ler-0 five to seven times more often than the wild-type isolate is described. The higher penetration frequency of isolate A22 is associated with an increased hypersensitive response, which includes callose deposition. Com- plementation analysis showed that the phenotype of this isolate is due to T-DNA insertion in an intronless gene denoted as ipa （increased penetration on A rabidopsis）. This gene is predicted to encode a protein of 702 amino acids with best matches to hypothetical proteins in other filamentous ascomycetes. The ipa gene is expressed in the wild-type isolate at low levels in culture and during infection of A. thaliana and B. napus.

关键词： NONHOST RESISTANCE BRASSICA-NAPUS SECONDARY STRUCTURE DISEASE RESISTANCE SALICYLIC-ACID OILSEED RAPE

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Thrombospondin I activates the macrophage Toll-like receptor 4 pathway

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Cellular & Molecular Immunology 2013年第6期10卷 506-512页

作者： Yanzhang Li Xinyu Qi Xiaopeng Tong Shuxia Wang Graduate Center for Nutritional Sciences University of Kentucky Lexington KY 40536 USA current address: College of Medicine Henan University Kaifeng 475004 China

Previously, we demonstrated that macrophages from thrombospondin 1 （TSP1）-deficient mice have a reduced inflammatory phenotype, suggesting that TSP1 plays a role in macrophage activation. In this study, we determined how TSP1 regulates macrophage function. We found that recombinant or purified piatelet human TSP1 treatment stimulated tumor-necrosis factor （TNF）-α expression in bone marrow-derived macrophages in a time- and dose-dependent manner. Toll-like receptor 4 （TLR4） expression （at the mRNA and protein levels） and nuclear factor-kappaB （NF-KB） activity were also stimulated by TSP1 treatment. The TSPl-mediated increase in TNF-a production was abolished in TLR4-deficient macrophages, suggesting that TSP1 activates macrophages through a TLR4-dependent pathway. TSP1 also stimulated TLR4 activation in macrophages in vivo. Furthermore, TSPl-mediated macrophage activation was attenuated by using a peptide or an antibody to block the association between TSP1 and CD36. Taken together, these data suggest that the stimulation of the macrophage TLR4 pathway by TSP1 is partially mediated by the interaction of TSP1 with its receptor, CD36.

关键词： CD36 macrophage thrombospondin 1 TLR4 TNF-α

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