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1.
This paper is prepared in honour of Professor E.T. Brown for his outstanding contributions to rock mechanics and geotechnical engineering and also for his personal influence on the first author's research career in geomechanics and geotechnical engineering. As a result, we have picked a topic that reflects two key research areas in which Professor E.T. Brown has made seminal contributions over a long and distinguished career. These two areas are concerned with the application of the critical state concept to modelling geomaterials and the analysis of underground excavation or tunnelling in geomaterials.Partially due to Professor Brown's influence, the first author has also been conducting research in these two areas over many years. In particular, this paper aims to describe briefly the development of a unified critical state model for geomaterials together with an application to cavity contraction problems and tunnelling in soils. 相似文献
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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
4.
Dr. Yahu A. Liu Dr. Qihui Jin Qiang Ding Dr. Xueshi Hao Tingting Mo Shanshan Yan Dr. Yefen Zou Dr. Zhihong Huang Xiaoyue Zhang Wenqi Gao Dr. Tom Y.-H. Wu Chun Li Dr. Badry Bursalaya Dr. Michael Di Donato Dr. You-Qing Zhang Lisa Deaton Dr. Weijun Shen Dr. Brandon Taylor Anwesh Kamireddy Dr. George Harb Dr. Jing Li Dr. Yong Jia Dr. Andrew M. Schumacher Dr. Bryan Laffitte Dr. Richard Glynne Dr. Shifeng Pan Dr. Peter McNamara Dr. Valentina Molteni Dr. Jon Loren 《ChemMedChem》2020,15(16):1562-1570
Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation. 相似文献
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何晓华 《安徽工业大学学报》2020,37(2):112-118
以江苏某企业的石英尾砂为研究对象,基于Jenike剪切理论,分析石英尾砂的物料性质、四棱锥料仓结构对重力流卸料的影响,考虑料仓卸料口尺寸和斜锥角对料仓内物料流动状态的影响,设计石英尾砂料仓及其辅助气力助流系统,且将其应用于江苏某企业试运行。结果表明:石英尾砂的含水率在14%(质量分数)时,物料的内摩擦角最大,物料粒径越细小,物料内摩擦角越大,但达150μm时增势趋于平缓;设计的石英尾砂料仓及其辅助气力助流系统可保障物料装卸料性能和防止物料堵仓;年产2万t石英尾砂的条件下,设计的石英尾砂料仓及其辅助气力助流系统可为企业节省200万元的生产成本,且社会环境效益显著。 相似文献
7.
UML在网络安全监控系统建模中的应用 总被引:4,自引:0,他引:4
本文首先介绍了UML的特性,然后运用UML对网络安全监控系统中的数据采集系统进行了可视化的建模,建立了系统的需求模型和设计模型的各种视图,最后总结了用UML进行系统需求分析和设计的优越性. 相似文献
8.
Yong Zhang Yuanlong Mo Xiaolan Zhou Jianqing Li 《Journal of Infrared, Millimeter and Terahertz Waves》2003,24(12):2085-2094
Recently disk-loaded waveguide has been widely used in high-power traveling wave tubes (HPTWT). It has been shown in many experiments that the interaction efficiency and output power can be increased greatly by injecting plasma into the vacuum microwave device. Using field analysis, the dispersion characteristics and the interaction impedance of the disk-loaded waveguide filled with plasma are analyzed in a strong longitudinal magnetic field. In conclusion, the frequency of the TM01 mode increases as the density of the plasma increases. It also can be found when the plasma density increases to a large scale, the TM01 mode of the disk-loaded waveguide overlaps the TG mode, these two modes couple each other and form the new hybrid modes. 相似文献
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10.
An optimization model for placement of wavelength converters to minimize blocking probability in WDM networks 总被引:7,自引:0,他引:7
Suixiang Gao Xiaohua Jia Chuanhe Huang Ding-Zhu Du 《Lightwave Technology, Journal of》2003,21(3):684-694
The introduction of wavelength converters in wavelength division multiplexing (WDM) networks can reduce the blocking probabilities of calls. In this paper, we study the problem of placing a given number of converters in a general topology WDM network such that the overall system blocking probability is minimized. The original contributions of this work are the following: 1) formulation of success probability in a network as a polynomial function of the locations of converters; 2) proposal of an optimization model of the converter placement problem as the minimization of a polynomial function of 0-1 variables under a linear constraint, so that standard optimization tools can be employed to solve the problem; and 3) design of a search algorithm that can efficiently find the optimal solution to the converter placement problem. Experiments have been conducted to demonstrate the effectiveness of the proposed model and the efficiency of the algorithm. 相似文献