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.     

Modeling of a constant Voltage transformer

This paper presents a comprehensive nonlinear model of the controlled constant voltage transformer also known as the ferroresonant transformer. Saturation is a normal mode of operation for this device. This paper derives an equivalent electrical circuit that relates to the physical structure of a typical design. The level of detail includes winding resistances, continuously nonlinear magnetizing inductances, tapped windings, and leakage inductances. The paper describes methods to extract the winding resistances, leakage inductances, and hysteresis loops of the transformer and how to fit the latter into single-valued nonlinear functions. The paper compares computer simulation results of the model with those obtained analytically and experimentally. The results show that the derived circuit will be very useful for designers of the ferroresonant transformer, which is used in uninterruptible power supplies.     

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.     

Treatment of acute lateral ankle ligament ruptures. A prospective 9-13-year follow-up study of three different therapies in 79 patients

In a prospective study of 79 patients with arthrographically verified acute ruptured lateral ankle ligaments we have evaluated the long-term results of three different treatments: operation and walking-cast, walking-cast alone and elastic bandage. The average follow-up period was 11 (9-13) years, and 32 parameters concerning interview, clinical and radiographic examinations were statistically analysed. The three kinds of treatment were found to be equal, since only one parameter showed significant difference at a 5% level using Fisher's exact and the Mann-Whitney test, and no difference by using the Kruskal-Wallis test for homogeneity. Residual disabilities and late complications, such as instability, pain on activity, and the number of secondary ligament reconstructions and talocrural arthroses were low. It was concluded that nonoperative treatment provided adequate results even after a decade.     

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.