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.     

Sequential Decoding of Convolutional Codes for Rayleigh Fading Channels

The performance of sequential decoding of long constraint length convolutional codes is evaluated for Rayleigh fading channels. Sequential decoding is not practical below a certain theoretical signal-to-noise ratio, and these theoretical limits are calculated for a number of modulation methods and code rates. As an example, with BPSK modulation, soft decisions and code rate 1/2, the theoretical signal-to-noise ratio per information bit is 5.7 dB. Above this limit the bit error rate can be made arbitrarily small by increasing the constraint length at no significant complexity cost. Furthermore, it is shown that with carefully chosen quantization steps, 8 level uniform quantization gives a negligible loss also for sequential decoding on a Rayleigh fading channel. Simulation results using 8 level quantization correspond well with the theoretical performance bounds. Also, the performance on a correlated channel with finite interleaving has been obtained. With an interleaver depth of 50×50 and a normalized doppler frequency equal to 0.01 we are only 0.5 dB away from the performance with perfect interleaving. Finally, bit error rate results show this scheme to compete well with Turbo codes.     

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.