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.     

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.     

Alpha blockaders--first or second line antihypertensive agents?

Alpha-receptor blockers reduce blood pressure by blocking of the alpha 1-receptors in the smooth muscle cells in the arteriolar walls. The heart pump function is not disturbed. Most studies have shown that the alpha-receptor blockers induce a reduction in plasma-triglycerides and an increase in the ratio between HDL- and LDL-cholesterol. They do not interfere with the metabolism of electrolytes, glucose or uric acid and have no negative effect on pulmonary function. Although long-term use does not induce a permanent increase in heart rate, some patients respond to initial therapy with faster heart rate and palpitations. The alpha-receptor blockers should not be used in patients with coronary heart disease if the patient is not on chronic beta-blockade. When these precautions are followed, the alpha-blockers can be used as first-line treatment--just like ACE-inhibitors and calcium-antagonists.     

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.     

A comparison among 1-, 3-, and 7-horn feeds for a 37-beam MBA

A very common multiple beam antenna (MBA) configuration consists of a collimating device illuminated by an array of feeds. The collimating device is usually a reflector or a lens. The feeds are usually horn antennas with a circular aperture. The reflector is usually offset-fed to eliminate aperture blockage; the lens is center fed. The antenna's feeds are excited to produce a finite number of beams, so as to provide contiguous coverage of the field of view. The designer is forced to minimize the angular spacing between adjacent beams in order to maximize the minimum gain over the antenna's field of view. On the other hand, the feed horn's aperture gain is maximized when the feed horn spacing and its aperture diameter are equal. This results in antenna efficiency of the order of 30% when a single feed horn is excited to produce a beam. When a cluster of 3 or 7 adjacent feed horns are excited to produce a single beam, antenna efficiency can be increased to 50%. When it is tolerable, several identical antenna apertures can be used to replace a single aperture configuration. In this case, each of M apertures produces approximately N/M beams of an MBA that produces N beams. Horns producing adjacent beams do not illuminate the same aperture. This permits the use of a much larger horn aperture for a given beam spacing. This results in reduced spillover, higher gain of each beam, and increased antenna efficiency of each aperture. This paper investigates the maximization of gain for several lens antennas. It shows that antenna gain is increased as its focal length is decreased. That is, a focal length-to-diameter ratio (F/D) less than 1 is preferred     

A thermodynamic evaluation of the c- cr- fe- w system

A thermodynamic evaluation of the C-Cr-Fe-W system has been made using a multi-sublattice model. A set of parameter values describing the Gibbs energy of each individual phase is given and a number of calculated sections of the C-Cr-Fe-W phase diagram are presented and compared with experimental data. Formerly with the Division of Physical Metallurgy, Royal Institute of Technology, Stockholm, Sweden     

Enzymatic biodiesel production: Technical and economical considerations

It is well documented in the literature that enzymatic processing of oils and fats for biodiesel is technically feasible. However, with very few exceptions, enzyme technology is not currently used in commercial‐scale biodiesel production. This is mainly due to non‐optimized process design and a lack of available cost‐effective enzymes. The technology to re‐use enzymes has typically proven insufficient for the processes to be competitive. However, literature data documenting the productivity of enzymatic biodiesel together with the development of new immobilization technology indicates that enzyme catalysts can become cost effective compared to chemical processing. This work reviews the enzymatic processing of oils and fats into biodiesel with focus on process design and economy.