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Zhuang CHENG Jianfeng WANG Matthew Richard COOP Guanlin YE 《Frontiers of Structural and Civil Engineering》2020,14(2):357
The development of a miniature triaxial apparatus is presented. In conjunction with an X-ray micro-tomography (termed as X-ray μCT hereafter) facility and advanced image processing techniques, this apparatus can be used for in situ investigation of the micro-scale mechanical behavior of granular soils under shear. The apparatus allows for triaxial testing of a miniature dry sample with a size of (diameter height). In situ triaxial testing of a 0.4–0.8 mm Leighton Buzzard sand (LBS) under a constant confining pressure of 500 kPa is presented. The evolutions of local porosities (i.e., the porosities of regions associated with individual particles), particle kinematics (i.e., particle translation and particle rotation) of the sample during the shear are quantitatively studied using image processing and analysis techniques. Meanwhile, a novel method is presented to quantify the volumetric strain distribution of the sample based on the results of local porosities and particle tracking. It is found that the sample, with nearly homogenous initial local porosities, starts to exhibit obvious inhomogeneity of local porosities and localization of particle kinematics and volumetric strain around the peak of deviatoric stress. In the post-peak shear stage, large local porosities and volumetric dilation mainly occur in a localized band. The developed triaxial apparatus, in its combined use of X-ray μCT imaging techniques, is a powerful tool to investigate the micro-scale mechanical behavior of granular soils. 相似文献
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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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Ole Wiborg Martin O'Connell Richard Thiele Martin Wichert Gunther Kolb 《化学工程与技术》2015,38(8):1308-1314
Many critical issues need to be addressed when microstructured reactors are manufactured in large unit volumes. The most crucial of these are cost, ease of production, and reliability. The lack of breakthrough manufacturing technology to provide high‐efficiency, low‐cost, high‐precision plates is a hindrance to the early market implementation of systems requiring metallic microstructured plates. This contribution focuses on the development and optimization of a combined embossing and bending tool for the quick and continuous manufacture of easily machined plates. 相似文献
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Dr. Hui Qiu Richard Caldwell Dr. Lesley Liu-Bujalski Dr. Andreas Goutopoulos Reinaldo Jones Justin Potnick Dr. Brian Sherer Dr. Andrew Bender Dr. Roland Grenningloh Dr. Daigen Xu Dr. Anna Gardberg Dr. Igor Mochalkin Dr. Theresa Johnson Dr. Ariele Viacava Follis Jared Head Dr. Federica Morandi 《ChemMedChem》2019,14(2):217-223
Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon. 相似文献
18.
Igboamalu Frank Nonso Ndjiongue Alain Richard Ferreira Hendrik Christoffel 《Telecommunication Systems》2020,73(4):521-530
Telecommunication Systems - Signals from indoor access points in a wireless fidelity suffer from high attenuation as a result of the thick walls and metal structures in the multilevel-storey... 相似文献
19.
Effendi Rusli Timothy O. Drews David L. Ma Richard C. Alkire Richard D. Braatz 《Journal of Process Control》2006,16(4):409-417
Robust nonlinear feedforward–feedback controllers are designed for a multiscale system that dynamically couples kinetic Monte Carlo (KMC) and finite difference (FD) simulation codes. The coupled codes simulate the copper electrodeposition process for manufacturing on-chip copper interconnects in electronic devices. The control objective is to regulate the current density subject to the condition that the steady-state fluctuation of the overpotential remains bounded within ±0.01 V. The controller designs incorporate a low-order stochastic model that captures the input–output behavior of the coupled KMC–FD code. The controllers achieve the objectives and the closed-loop responses implemented on the low-order model and the coupled KMC–FD code match well within stochastic variations. The nonlinear feedforward control reduces the rise time of the controller response while the feedback control ensures robustness in the presence of model uncertainty. 相似文献
20.
The Intellectual Development of Science and Engineering Students. Part 2: Teaching to Promote Growth
As college students experience the challenges of their classes and extracurricular activities, they undergo a developmental progression in which they gradually relinquish their belief in the certainty of knowledge and the omniscience of authorities and take increasing responsibility for their own learning. At the highest developmental level normally seen in college students (which few attain before graduation), they display attitudes and thinking patterns resembling those of expert scientists and engineers, including habitually and skillfully gathering and analyzing evidence to support their judgments. This paper proposes an instructional model designed to provide a suitable balance of challenge and support to advance students to that level. The model components are (1) variety and choice of learning tasks; (2) explicit communication and explanation of expectations; (3) modeling, practice, and constructive feedback on high‐level tasks; (4) a student‐centered instructional environment; and (5) respect for students at all levels of development. 相似文献