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.     

Design and Characterization of a New pVII Combinatorial Phage Display Peptide Library for Protease Substrate Mining Using Factor VII Activating Protease (FSAP) as Model

We describe a novel, easy and efficient combinatorial phage display peptide substrate-mining method to map the substrate specificity of proteases. The peptide library is displayed on the pVII capsid of the M13 bacteriophage, which renders pIII necessary for infectivity and efficient retrieval, in an unmodified state. As capture module, the 3XFLAG was chosen due to its very high binding efficiency to anti-FLAG mAbs and its independency of any post-translational modification. This library was tested with Factor-VII activating protease (WT-FSAP) and its single-nucleotide polymorphism variant Marburg-I (MI)-FSAP. The WT-FSAP results confirmed the previously reported Arg/Lys centered FSAP cleavage site consensus as dominant, as well as reinforcing MI-FSAP as a loss-of-function mutant. Surprisingly, rare substrate clones devoid of basic amino acids were also identified. Indeed one of these peptides was cleaved as free peptide, thus suggesting a broader range of WT-FSAP substrates than previously anticipated.     

Fast internal dynamics in polyelectrolyte gels measured by dynamic light scattering

Summary Dynamic light scattering was used to investigate the dynamics of sodium poly(styrene sulfonate) and fully neutralized poly(acrylic acid) gels as a function of the degree of swelling and weight ratio of cross-linking agent. It was shown that the collective diffusion coefficient increases with increasing degree of swelling and that the diffusion coefficient shows stronger concentration dependence than predicted by scaling arguments. For gel samples measured at the swelling equilibrium, the diffusion coefficient increases with increasing gel concentration for both gel systems.     

Manufacturing method for monolithic dye-sensitised solar cells permitting long-term stable low-power modules

A manufacturing technique for monolithic dye-sensitised solar cells is presented. Encapsulated modules designed for indoor low-power applications have been prepared using industrial methods and equipment. Under certain conditions (light intensity <5000 lx, temperature between –10°C and 50°C, and relative humidity of appr. 50%), the modules have performed well and shown excellent long-term stability. Moreover, modules withstand illumination in combination with storage at 100% relative humidity. However, a certain degradation of the module performance takes place at illuminations exceeding 5000 lx and temperatures exceeding 50°C.     

The Region 1 & 3 Broadcasting‐Satellite Service Plan after WRC‐03

The 1977 Broadcasting‐Satellite Service (BSS) Plan for Region 1 & 3 had been widely acknowledged to be out‐of‐date by the late 1980s. Development of digital modulation in the early 1990s provided an opportunity to update the technical provisions of the Plan to make it more economically viable. After a decade of work and three World Radiocommunication Conferences (WRCs), the revision of Region 1 & 3 BSS Plan was finally completed in 2003. The new Plan increased channel assignments from 5 to 10 analog‐equivalent channels for each country in Region 1, and from 4 to 12 channels for each country in Region 3. Yet, despite the increase in capacity, the new Plan is surprisingly similar to the original one in terms of the technical parameters. It is still based on national coverage, and the channel plan, orbital location, orbital spacing, and polarization are also the same. As a result, the new Plan is no more economically viable to implement than the old. To create economically viable BSS systems would most likely require modifications to the assignment in the Plan. Yet, modification procedures were made more difficult to apply after replanning. Less future implementation of BSS networks than would otherwise have occurred can be expected, and an inefficient usage of these frequency bands will likely result. On the other hand, less implemented systems will mean more capacity set aside for future use. This is important for countries that currently do not have satellite operations. In the end, BSS replanning reflects the eternal conflict between efficient usage and guaranteed future access. Copyright © 2005 John Wiley & Sons, Ltd.     

汽车空调冷凝器腐蚀试验的表征与评价

介绍了汽车空调冷凝器的腐蚀试验程度及方法，对试验后的冷凝器进行了密封性检查，并用光学显微镜和扫描电镜检测和分析了材料的显微结构，焊接质量，腐蚀性质及其腐蚀深度等。通过对冷凝器的宏微观检查与表征，评价了冷凝器质量的优劣，提出了改进措施与建议。     

New CAMAC based data acquisition and beam control system for Lund nuclear microprobe

A new CAMAC based data acquisition system has been installed at the Lund Nuclear Microprobe facility. This paper reports on the development and present status of the data acquisition system. The system is a true multiparameter CAMAC based system with fast Fera bus readout and in crate memory buffer. The user interface is based on Sparrow Kmax software for a Power Macintosh platform. The system read out and tag the event data with position on-line, which make fast on-line monitoring of spectra or element maps possible.Simultaneously, all data can be saved event by event for off-line analysis. The beam scanning part is software controlled through a timed D/A converter, this allows fast scanning of the beam. With a CCD-camera and video card the area to be analysed could be defined directly from the image, and the sample position can be moved. Any kind of irregular scan patterns could be defined.     

B2O3/TiO2-ZrO2催化剂上环己酮肟的气相Beckmann重排反应

用共沉淀法制备了TiO2-ZrO2复合氧化物载体，BET，DTA，XRD表征结果表明，该复合载体具有较大的比表面和较好的热稳定性，对于环己酮肟气相Beckmann重排反应制己内酰胺，用复合载体制备的B2O3／TiO2-ZrO2催化剂，比分别以TiO2,ZrO2为载体所制备的B2O3/TiO2和B2O3／ZrO2催化剂具有更高的活性和选择性，实验表明，催化剂表面中等强度的酸位是环己酮肟气相Beckmann重排反应的有效活性中心。     

考虑抗力退化的公路钢筋混凝土梁抗弯强度可靠性分析

本文采用了一个时变荷载模型和一个考虑了钢筋锈蚀，钢筋屈服拉力，混凝土抗压强度和粘结力等多个影响因素的多参数抗力劣化模型，对公路钢筋混凝土梁抗弯强度可靠性在服役期内的变化趋势进行了研究，并针对一实例对各影响参数对可靠性分析的敏感性进行了分析。     

鼻咽癌药物我成像定位仪的光学设计

对药物荧光鼻咽癌定位的光学系统进行理论分析，给出了该系统的光学设计方法和设计结果。光学系统设计包括，激光器出射光束与光纤高效率耦合技术，同光轴非接触两光纤间的光束耦合技术以及获得较好的像清晰度和衬度的技术。