The Critical Role of Passive Permeability in Designing Successful Drugs

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.     

沉管隧道水下最终接头施工技术初探

简述了沉管隧道水下最终接头施工技术的应用现状，结合具体隧道工程实例，从外模工程、混凝土结构两方面介绍了最终接头施工技术，表明了该技术具有运用价值。     

机动武器系统的含间隙动力学研究--下篇:系统仿真

本文把中篇建立的间隙铰模型引入多体系统动力学分析中,得到了一种处理含间隙多体系统动力学问题的一般方法.应用这种方法对机动武器的发射过程进行了原理性的仿真,验证了前面建立的碰撞模型和间隙模型,并分析了间隙对导弹运动状态的影响.导弹发射过程具有变拓扑的特点,本文方法提供了一种处理这类问题的思路.     

A framework of virtual prototyping environment for the design and analysis of mechanical mechanism with clearance

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.     

论剪切质量的提高

通过对飞剪剪切长度，精度，剪刃间隙和压板机构等参数的优化，来提高钢板的剪切质量。     

排气系统在注射模中的应用

介绍了排气系统在注射模中的重要性,排气系统位置的选择,排气系统的种类以及应用等     

NUMERICAL SIMULATION OF TIP-CLEARANCE FLOW IN CASCADE

1 .　ＩＮＴＲＯＤＵＣＴＩＯＮＴｉｐ ｃｌｅａｒａｎｃｅｆｌｏｗｓｏｃｃｕｒｉｎｖａｒｉｏｕｓｅｎｇｉｎｅｅｒ ｉｎｇａｐｐｌｉｃａｔｉｏｎｓｓｕｃｈａｓａｘｉａｌ ｆｌｏｗ ｐｕｍｐｓａｎｄｄｕｃｔ ｅｄｐｒｏｐｅｌｌｅｒｓ .Ｔｈｅｉｎｅｒｔｉａｌｆｏｒｃｅｓａｃｔｉｎｇｕｐｏｎｔｈｅｆｌｕｉｄｉｎｔｈｅｎａｒｒｏｗ ｇａｐｂｅｔｗｅｅｎｂｌａｄｅｔｉｐａｎｄｔｈｅｓｕｒｒｏｕｎｄｉｎｇｗａｌｌａｒｅｓｕｆｆｉｃｉｅｎｔｔｏ ｇｅｎｅｒａｔｅａｔｉｐｌｅａｋａｇｅｖｏｒｔｅｘｏｎｔｈｅｓｕｃｔｉｏｎｓ…     

自由锻锤上冷冲厚板新工艺

介绍了自由锻锤上冷冲厚板工艺的特点和模具主要结构。以及如何解决凸凹模间隙、选用小间隙冲孔时刃口磨损加剧的问题。研制出了降低磨损。提高模具寿命的润滑剂配方。设计了适合自由锻锤上厚板冲孔的模具，对在自由锻锤上厚板冲孔进行了有益的尝试。扩大了自由锻设备的加工范围。解决了不具备大型压力机情形下的生产难题。     

连轧管机轧辊轴承的调整、维护及保养

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。     

Association of IgG1 Antibody Clearance with FcγRIIA Polymorphism and Platelet Count in Infliximab-Treated Patients

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.