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61.
Dr. Blijke S. Kroezen Gabriele Conti Benedetta Girardi Dr. Jonathan Cramer Dr. Xiaohua Jiang Dr. Said Rabbani Jennifer Müller Maja Kokot Enrico Luisoni Prof. Daniel Ricklin Dr. Oliver Schwardt Prof. Beat Ernst 《ChemMedChem》2020,15(18):1706-1719
Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewisx has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewisx and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved. 相似文献
62.
This paper presents an integrated passive damping approach in hybrid metal-CFRP parts for structural applications. In this concept a viscoelastic material is embedded in the joint zone of the hybrid component. To examine the connection strength single-lap-joint specimens were produced and tested and the influence of the used material combinations, different surface structures, and different process parameters i.e. the moment of cross-linking were evaluated. Afterwards, the metal-CFRP hybrids were tested in quasi-static tests to assess their connection strength and failure behaviour. Dynamic cyclic tensile tests with step-wise increased loading conditions were performed to determine the specimens damping behaviour and to estimate their fatigue performance. Finally, these results are compared to a state of the art metal-CFRP hybrid with rivets connecting both materials. 相似文献
63.
Mingchang Lin Yufei Zhang Guosong Chen Ming Jiang 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(45):6065-6070
Glyco‐mimicking nanoparticles (glyco‐NPs) with Förster resonance energy transfer (FRET) donor and acceptor groups formed via dynamic covalent bond of benzoboroxole and sugar from two complementary polymers are prepared. The glyco‐NPs are proved to be quite stable under physiological conditions but sensitive to pH. So the glyco‐NPs can be internalized by dendritic cells with integrity and nontoxicity and then dissociate within the acidic organelles. This particle dissociation is directly observed and visualized in vitro, for the first time via the FRET measurements and fluorescent microscopy. This feature makes controlled release of drug or protein by glyco‐NPs possible, i.e., when model antigen Ovalbumin is loaded in the glyco‐NPs, the released Ovalbumin in dendritic cells stimulates T cells more efficiently than the free Ovalbumin itself as a result of the enhanced antigen processing and presentation. Thus, the results enlighten a bright future of the glyco‐NPs in immunotherapy. 相似文献
64.
介绍了超高性能混凝土(UHPC)的制备原理和性能特点,对UHPC国内外研究和应用情况进行了综述,指出了我国UHPC研究和应用中存在的问题。结果表明:UHPC是一种具有优异的力学性能、耐久性能和环保效益的新型水泥基复合材料。国外在UHPC理论研究和应用研究方面都取得了大量成果,在实际工程中已经获得了广泛的应用;近年来我国在理论研究和应用方面也得到了快速发展;如何简化UHPC制备工艺、降低生产成本、补偿自收缩是今后的主要研究方向,完善相关规范标准以更好地指导UHPC现浇工程应用是目前首要解决的问题。随着环保和可持续发展理念的日益重视,UHPC这种低碳环保材料将有广阔的发展前景。 相似文献
65.
铁尾矿砂的储量日趋增加,要减小铁尾矿坝的风险、提高铁尾矿砂的利用率,须明确铁尾矿砂的力学特性.通过对铁尾矿砂静力特性及动力特性的分析发现,尾矿砂的粒径分布是决定尾矿坝稳定及铁尾矿砂再生利用的主要因素之一,细粒含量、干密度、含水率等因素对铁尾矿砂动力特性有一定影响.再生利用铁尾矿砂的主要方式是将铁尾矿砂混凝土、改性铁尾矿砂用作工程材料,水泥、石灰、纤维是改性铁尾矿砂的主要材料.最后指出需进一步研究新型材料取代传统改性材料改善铁尾矿砂的力学特性,从而提高资源利用率. 相似文献
66.
In this paper, we consider the classical finite mixture model, which is an effective tool for modeling lifetime distributions for random samples from heterogeneous populations. We discuss new results on stochastic comparison for two finite mixtures when each of them is drawn from one of the following semiparametric families, i.e., proportional hazards, accelerated lifetime and proportional reversed hazards. 相似文献
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69.
Functional expression and synergistic cooperation of xylan‐degrading enzymes from Hypocrea orientalis and Aspergillus niger 下载免费PDF全文
70.
Variations of Incomplete Open Cubes is the major project by the twentieth-century conceptual artist Sol LeWitt. In this paper we interpret the enumerative component of the project as embeddings of graphs. This formulation permits use of an algorithm to check the completeness of the list of the structures produced by the artist. Our conclusion is that the artist found the correct number of structures (that is, 122), but that his list contains a mistake in the presentation of a pair of incomplete cubes, a discovery that appears not to have been noted before. 相似文献