Molecular Dynamics Simulation of the Crystallizable Fragment of IgG1—Insights for the Design of Fcabs

An interesting format in the development of therapeutic monoclonal antibodies uses the crystallizable fragment of IgG1 as starting scaffold. Engineering of its structural loops allows generation of an antigen binding site. However, this might impair the molecule’s conformational stability, which can be overcome by introducing stabilizing point mutations in the CH3 domains. These point mutations often affect the stability and unfolding behavior of both the CH2 and CH3 domains. In order to understand this cross-talk, molecular dynamics simulations of the domains of the Fc fragment of human IgG1 are reported. The structure of human IgG1-Fc obtained from X-ray crystallography is used as a starting point for simulations of the wild-type protein at two different pH values. The stabilizing effect of a single point mutation in the CH3 domain as well as the impact of the hinge region and the glycan tree structure connected to the CH2 domains is investigated. Regions of high local flexibility were identified as potential sites for engineering antigen binding sites. Obtained data are discussed with respect to the available X-ray structure of IgG1-Fc, directed evolution approaches that screen for stability and use of the scaffold IgG1-Fc in the design of antigen binding Fc proteins.     

水泥生产工艺与混凝土耐久性的关系

1 影响混凝土耐久性的因素 水泥是混凝土的一种重要原料,它的性能对混凝土性能有十分重要的影响.混凝土诸多性能中耐久性非常重要,如果混凝土结构物没有达到预期使用年限而过早地被破坏,不但经济损失巨大而且危及人们的安全.黄士元等[1]将混凝土破坏的原因分为四大类:①磨损;②物理因素的破坏;③化学作用的破坏;④钢筋锈蚀造成的破坏.     

基于DSP的小型捷联惯性航姿系统研究

针对微小型应用场合,设计了基于DSP的导航计算机,成功构建了低成本小型捷联航姿系统.重点描述了DSP导航计算机的硬件设计思路,特别是"数字信号处理器(DSP)+单片机(MCU)"的特殊的主从式双CPU结构.扼要介绍了系统软件的框架结构.实验表明基于DSP的捷联惯性航姿系统,性能稳定、达到了设计精度,降低了成本,成功的实现了系统的小型化.DSP导航计算机体积仅为65mm×80mm×10mm,对导航系统在小型化领域推广应用具有实际意义.     

狂印假币逃脱不了法律的严惩

近些年来,社会上的一些不法之徒利用印刷技术疯狂伪造假币,违法犯罪活动呈现明显上升趋势,有些案情闻后着实让人触目惊心。最近一些网络、报纸又爆料出令人震惊的消息,说犯罪团伙肖某、张某等人为首的犯罪团伙纠集多名印刷工人,在三     

焦化酚氰废水工艺改进及综合利用

针对朝阳钢铁焦化酚氰废水工艺存在的问题,通过应用斜孔塔盘、可提升式曝气器和改造臭氧催化氧化系统等措施,使酚氰废水出水达标排放;并将生产排污水及富余脱硫液回用于酚氰废水,实现了废水的综合利用。     

Synthesis of chiral polymers having camphanediol moieties and their applications on the optical resolution of some racemates

Optically active exo-exo-2,3-camphanediol (CPO) (3) was synthesized from (+)-camphor. Chiral polymers poly(CPO-co-TDI) ( 6 ) and poly(CPO-co-IPDI) ( 7 ) were synthesized by the step polymerization of chiral compound CPO ( 3 ) with toluene-2,4-diisocyanate (TDI) and isophorone diisocyanate (IPDI). To investigate the stereo structure of the chiral polymers, two kinds of model compounds, exo-exo-2,3-di[(phenylamido)oxy]camphane ( 4 ) and exo-exo-2,3-di[(propylamido)oxy]camphane ( 5 ), related to polymers ( 6 ) and ( 7 ) were synthesized. Chiroptical characteristics and stereo structures of the chiral polymers were investigated using a circular dichroic spectrometer. The results obtained in this investigation suggest that the chiral polymers ( 6 ) and ( 7 ) have no one-handed helix conformation. The optical resolution ability as chiral adsorbent for HPLC of the chiral polymers was investigated. It was found that chiral polymers ( 6 ) and ( 7 ) are effective for the optical resolution of some racemates. © 1995 John Wiley & Sons, Inc.     

Demonstration of delayed hypersensitivity in Chlamydia trachomatis salpingitis in monkeys: a pathogenic mechanism of tubal damage

The role of delayed hypersensitivity in the pathogenesis of Chlamydia t trachomatis salpingitis was studied in the monkey "pocket" model. Pigtailed monkeys (Macaca nemestrina) were sensitized by inoculation of live C. trachomatis organisms (E/UW-5/Cx) into subcutaneous pockets containing salpingeal autotransplants. At 21 days, affinity-purified recombinant C. trachomatis heat-shock protein (rhsp60) was injected into pockets either previously sensitized with C. trachomatis or not sensitized in the same monkey. Delayed-type hypersensitivity reaction was observed, characterized by mononuclear cell infiltration with peak reaction at 48 h. Injection of rhsp60 into the pockets of a naive animal did not induce inflammation. This study showed that C. trachomatis infection in monkeys induced delayed hypersensitivity, which is mediated by hsp60. Histologic findings of the salpinx were consistent with delayed hypersensitivity reaction observed in ocular C. trachomatis infection, further suggesting a similar pathogenesis for both salpingitis and trachoma.     

轮胎厂蒸汽的生产使用和管理

介绍了轮胎厂蒸汽的生产、使用及管理过程中应该注意的问题。就如何以最低的成本生产蒸汽、以最佳的效果使用蒸汽、以最科学的方法管理蒸汽提出了自己的见解。特别对锅炉的配置与运行、管道及附件的正确安装、管道保温层的临界厚度及冷凝水的回收等问题进行了探讨。     

TOWNHOUSE发展的探讨

T0WNHOUSE是一种典型的独立住宅形式.其特点已经包含在其名称中,即既要有TOWN(城镇)的支持,又要有HOUSE(独立住宅)的低密度品质.而传统的、地域和乡土的文化是使TOWN的氛围、HOUSE的品质和室外的环境,这些物质环境获得灵魂的重要要素.作者针对当前TOWNHOUSE的现状,分析了其特点、问题及发展趋势.