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.     

Dual command travel times and miniload system throughput with turnover-based storage

We analyze travel times for automated storage/retrieval systems. In particular, we apply our travel time model to turnover-based storage systems and determine the mean and variance of dual command travel times. We present detailed numerical results for selected rack shape factors and ABC inventory profiles. We then investigate the effect of alternative rack configurations on travel time performance measures. We also show how to determine the throughput of miniload systems with turnover-based storage and exponentially distributed pick times.     

Performance of Indoor Infrared Wireless CDMA Systems with Angle Diversity

Indoor infrared communication systems is one of the possible ways of offering data rates in excess of 100 Mbit/s without the need for wiring. Multiple users can share an infrared channel by code division-multiple access (CDMA) techniques. However, the CDMA system performance is limited by both background noise and co-channel interference. In this paper we study the use of angle diversity for mitigating the effects of the noise and interference. The system considered uses on-off shift keying modulation with multibeam transmitters and imaging receivers. The overall system performance for different diversity combining techniques is evaluated and compared to a system without diversity. Numerical results for a 2-user CDMA system indicate that signal to noise and interference ratio (SNIR) improvement (over systems with no diversity) of 5 dB is obtained for at least 50% of an ensemble of 10000 sample evaluations. The generalized selection combining (GSC)--a new diversity technique yet to be implemented for infrared systems--offers the best performance even with its reduced complexity.     

Fractal-wavelet image denoising revisited.

The essence of fractal image denoising is to predict the fractal code of a noiseless image from its noisy observation. From the predicted fractal code, one can generate an estimate of the original image. We show how well fractal-wavelet denoising predicts parent wavelet subtress of the noiseless image. The performance of various fractal-wavelet denoising schemes (e.g., fixed partitioning, quadtree partitioning) is compared to that of some standard wavelet thresholding methods. We also examine the use of cycle spinning in fractal-based image denoising for the purpose enhancing the denoised estimates. Our experimental results show that these fractal-based image denoising methods are quite competitive with standard wavelet thresholding methods for image denoising. Finally, we compare the performance of the pixel- and wavelet-based fractal denoising schemes.     

The role of perspective in the accessibility of goals during reading.

An implicit assumption of several causal reasoning models is that readers adopt the goals of a narrative's protagonist during text comprehension. In apparent violation of this assumption, readers participating in Experiment 1 of the present study drew inferences relevant to a protagonist's goal even when that goal was already satisfied from the perspective of the protagonist. In Experiments 2 and 3, participants were explicitly asked to view the text situation from the point of view of the protagonist. In this case, the goals of the reader and the protagonist should be the same. In these experiments, participants focused on the goals of the protagonist only when those goals had not been satisfied from the perspective of the protagonist. These results are discussed in terms of reader- and character-based perspectives and in terms of text characteristics that cue perspective taking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preparation of the international employee: Career and consultation needs.

Studied how 26 senior managers and 47 senior professional technical staff (recently repatriated) of 4 US owned multinational organizations viewed their international posting, specifically with respect to career path satisfaction. Results of satisfaction scales indicate that many Ss felt under-prepared for their international assignment. It is suggested that a comprehensive international employee development program should assess, provide feedback, and coach individuals on career path, culture shock and adjustment, and performance issues prior, during, and on return from the expatriate assignment. Results suggest that opportunities exist for individual and organizational intervention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rheological and drug‐release behaviour of a scleroglucan gel matrix at different drug loadings

The aim of this study was to investigate the drug‐loading effects on release and mechanical properties of a scleroglucan gel, with the intention of considering them in delivery systems formulations. The rheological and kinetic properties of a 2 % w/w scleroglucan gel matrix loaded with 0, 0.02, 0.04, 0.06, 0.2 and 0.4 % w/w of theophylline (Th, used as a model drug) were investigated. Rheological measurements were performed in a controlled‐stress rotational‐shear rheometer under isothermal conditions. For theophylline release from the gel a flat Franz cell was used and the kinetic parameters were derived applying a semi‐empirical power law. The influence of scleroglucan molar weight on kinetic and rheological behaviour was also studied. Results suggest two possible effects of drug loading on the gel network: in the 0.04–0.06 % w/w Th range a plasticizing effect and in the 0.2–0.4 % w/w Th range a rigidization effect. In the first range mentioned, the changes in the gel structural properties tested by means of rheological measurements are coincident with changes in drug‐release kinetics. Copyright © 2005 Society of Chemical Industry