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Dr. Li Di Prof. Per Artursson Dr. Alex Avdeef Prof. Leslie Z. Benet Prof. J. Brian Houston Dr. Manfred Kansy Edward H. Kerns Prof. Hans Lennernäs Dr. Dennis A. Smith Prof. Kiyohiko Sugano 《ChemMedChem》2020,15(20):1862-1874
Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients. 相似文献
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A framework of virtual prototyping environment for the design and analysis of mechanical mechanism with clearance 总被引:7,自引:0,他引:7
Mechanical mechanisms with clearance abound in technological fields such as robotics, machine and steam turbine industry. The dynamic performance of these mechanisms in working condition can be achieved provided that the effects of the different on the mechanisms (such as mechanism dynamics, technological effects and thermal behaviour) are thoroughly understood. Virtual prototyping provides an integration of multi-domain dynamic simulation for the design and analysis process. In the current paper, a framework of virtual prototyping environment for the design and analysis of mechanical mechanism with clearance is presented. A case study with such a simulation strategy is studied for the optimum design and analysis of the technological parameter. 相似文献
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NUMERICAL SIMULATION OF TIP-CLEARANCE FLOW IN CASCADE 总被引:1,自引:1,他引:0
Chen Long Yang Chen jun Wang Guo qiangSchool of Naval Architecture Ocean Engineering Shanghai Jiaotong University Shanghai China 《水动力学研究与进展(B辑)》2003,15(1)
1 . INTRODUCTIONTip clearanceflowsoccurinvariousengineer ingapplicationssuchasaxial flow pumpsandduct edpropellers .Theinertialforcesactinguponthefluidinthenarrow gapbetweenbladetipandthesurroundingwallaresufficientto generateatipleakagevortexonthesuctions… 相似文献
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本文介绍了应用于MPM连轧机轧辊上的四列圆锥滚子轴承的结构特性及其调整、维护、保养,旨在提高轴承的使用寿命。 相似文献
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Gilles Thibault Gilles Paintaud Hsueh Cheng Sung Laurie Lajoie Edouard Louis the GETAID Celine Desvignes Herv Watier Valrie Gouilleux-Gruart David Ternant 《International journal of molecular sciences》2021,22(11)
The FcγRIIA/CD32A is mainly expressed on platelets, myeloid and several endothelial cells. Its affinity is considered insufficient for allowing significant binding of monomeric IgG, while its H131R polymorphism (histidine > arginine at position 131) influences affinity for multimeric IgG2. Platelet FcγRIIA has been reported to contribute to IgG-containing immune-complexe clearance. Given our finding that platelet FcγRIIA actually binds monomeric IgG, we investigated the role of platelets and FcγRIIA in IgG antibody elimination. We used pharmacokinetics analysis of infliximab (IgG1) in individuals with controlled Crohn’s disease. The influence of platelet count and FcγRIIA polymorphism was quantified by multivariate linear modelling. The infliximab half-life increased with R allele number (13.2, 14.4 and 15.6 days for HH, HR and RR patients, respectively). It decreased with increasing platelet count in R carriers: from ≈20 days (RR) and ≈17 days (HR) at 150 × 109/L, respectively, to ≈13 days (both HR and RR) at 350 × 109/L. Moreover, a flow cytometry assay showed that infliximab and monomeric IgG1 bound efficiently to platelet FcγRIIA H and R allotypes, whereas panitumumab and IgG2 bound poorly to the latter. We propose that infliximab (and presumably any IgG1 antibody) elimination is partly due to an unappreciated mechanism dependent on binding to platelet FcγRIIA, which is probably tuned by its affinity for IgG2. 相似文献
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分析了水泵底架原冲压成形工艺存在的问题,提出了新的成形工艺方案,介绍了新工艺中关键工序的模具结构以及模具加工、现场调试应注意的事项。经生产验证,改进后的工艺与模具结构合理,产品质量及生产效率大大提高。 相似文献
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