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.     

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 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.     

Emission Of Volatile And Semivolatile Organic Compounds From Waterborne Paints – The Effect Of The Film Thickness

A waterborne paint was applied to tin plated steel sheets with three different film thicknesses. The emission of volatile and semivolaile organic compounds ((S) VOCs) from the samples was measured in small climatic chambers under standard conditions over a two-week period. The purpose of the study was to evaluate the effect of the film thickness on the emission rate decay. First order decay models, including sink effects for the high boiling (S) VOCs, were fitted to the concentration versus time data. The results showed that the first order rate constants decrease with increasing film thickness. In uddition, the results indicated that the emissions of the (S)VOCs in the waterborne paint film seemed to be controlled by evaporation. The thicknesses of paint films used in climatic chamber tests to estimate emission rates for product compurison or emission prediction must be known in order to prevent erroneous conclusions     

An overall model for maintenance optimization

This paper presents an approach for identifying the optimal maintenance schedule for the components of a production system. Safety, health and environment objectives, maintenance costs and costs of lost production are all taken into consideration, and maintenance is thus optimized with respect to multiple objectives. Such a global approach to maintenance optimization requires expertise from various fields, e.g., decision theory, risk analysis and reliability and maintenance modelling. Further, a close co-operation between management, maintenance personnel and analysts is required to achieve a successful result. In the past this has been a major obstacle to the extensive use of proper maintenance optimization methods in practice, and techniques to promote the communication between the involved parties of the optimization process is an essential element in the suggested approach. A simple step by step presentation of the required modelling is provided. Contrary to most current methods of RCM (Reliability Centered Maintenance), the approach is based on an analytic model, and therefore gives a sound framework for carrying out a proper maintenance optimization. The approach is also flexible as it can be carried out at various levels of detail, e.g., adopted to available resources and to the managements willingness to give detailed priorities with respect to objectives on safety vs production loss.     

Existence of discrete-time LQG-controllers

Existence results for the LQG-controller are investigated. An infimal Riccati equation based controller may potentially give closed loop eigenvalues on the unit circle. Assuming left and right invertibility it is shown that there exists an optimal controller if and only if the Riccati equation based controller stabilizes the closed loop system after removal of all its unobservable and uncontrollable modes. Furthermore this reduced controller is the optimal controller, and its transfer function is unique. This existence condition is a considerable simplification of the more general geometric condition recently derived by Trentelman and Stoorvogel.