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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   
2.
3.
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.
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   
5.
乙二胺与氯乙酸乙酯经取代、环合反应制得2-哌嗪酮,2-哌嗪酮与Boc酸酐进行氨基保护反应后,再与五硫化二磷进行硫代反应制得4-(N-叔丁氧羰基)-2-哌嗪硫酮,其与三氟乙酰肼经取代、环合、脱叔丁氧羰基成盐,得标题化合物,总收率为45.7%(以氯乙酸乙酯计)。为磷酸西他列汀中间体的工业化生产提供了一条较理想的工艺路线。  相似文献   
6.
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  
海沫  徐正权 《现代计算机》2004,(1):29-32,49
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.
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   
9.
X80焊管H_2S环境应力腐蚀开裂行为研究   总被引:9,自引:1,他引:8  
采用三点弯曲加载法和微电极扫描测试技术,研究了X80高强度级管线钢及其焊缝区的抗H2S环境应力腐蚀开裂(SSCC)行为。测定了焊接接头的显微硬度分布,分析了显微组织结构、力学性能及抗腐蚀性能之间的相关性。研究表明,热影响区(HAZ)对应力腐蚀开裂最为敏感,母材的纵向和横向取样对应力腐蚀敏感性影响不显著,薄壁管材比厚壁管材有较好的抗H2S环境应力腐蚀性能。HAZ晶粒粗大、硬度高,局部腐蚀倾向大,由此导致该区SSCC敏感性高。  相似文献   
10.
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   
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