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.     

Nonlinear system identification using BBO-based multilayer perceptron network method

Microsystem Technologies - Recently, nonlinear system identification has received increasingly more attention due to its promising applications in engineering fields. It has become a challenging...     

The ‘Hoare logic’ of concurrent programs

Summary Hoare's logical system for specifying and proving partial correctness properties of sequential programs is generalized to concurrent programs. The basic idea is to define the assertion {P} S {Q} to mean that if execution is begun anywhere in S with P true, then P will remain true until S terminates, and Q will be true if and when S terminates. The predicates P and Q may depend upon program control locations as well as upon the values of variables. A system of inference rules and axiom schemas is given, and a formal correctness proof for a simple program is outlined. We show that by specifying certain requirements for the unimplemented parts, correctness properties can be proved without completely implementing the program. The relation to Pnueli's temporal logic formalism is also discussed.     

SlideBar: Analysis of a linear input device

The SlideBar is a physical linear input device for absolute position control of 1° of freedom, consisting of a physical slider with a graspable knob positioned near or attached to the keyboard. Its range of motion is directly mapped to a one dimensional input widget such as a scrollbar. The SlideBar provides absolute position control in one dimension, is usable in the non-dominant hand in conjunction with a pointing device, and offers constrained passive haptic feedback. These characteristics make the device appropriate for the common class of tasks characterized by one-dimensional input and constrained range of operation. An empirical study of three devices (SlideBar, mouse controlled scrollbar, and mousewheel) shows that for common scrolling tasks, the SlideBar has a significant advantage over a standard mouse controlled scrollbar in user preference. In addition, users tended to prefer it over the mousewheel (without statistical significance).     

Reduction of Radiation-Induced Hair Loss by Topical Application of Radioprotectors

ABSTRACT

Our transdermal permeation studies of radioprotectors in permeation-enhancing vehicles led us to hypothesize that radiation-induced hair loss could be reduced by topical application of radioprotectors. In the present study we used a hair regrowth assay in “plucked” mice to measure the radioprotective effectiveness of WR-1065, cysteine and TEMPOL when they were dissolved in a variety of vehicles, i.e., saline, dimethyl formamide (DMF), propylene glycol (PG), dimethyl sulfoxide (DMSO), ethanol. Protector effectiveness varied with radiation dose and vehicles. At 600 R, WR-1065 or cysteine, in any vehicle, reduced radiation-induced baldness scores; at 800 R, only WR-1065 in DMF and cysteine in saline, produced some protection. TEMPOL in ethanol produced protection at both the 600 and 800 R. Results suggest that suitably chosen topical application of protector/vehicle combinations can reduce radiation-induced hair loss.     

A broadband PHEMT MMIC distributed doubler using high-pass drain line topology

A broadband frequency doubler, based on distributed amplifier techniques, has been designed to operate from 11 to 21 GHz. In order to reject the fundamental signal over a broadband frequency range, the conventional low-pass drain line structure was replaced with the high-pass structure. This topology can suppress fundamental signals over broadband without any balanced structure so that the chip size can be more compact. Measured conversion losses of better than 10 dB from 11 to 21 GHz input frequencies are achieved with fundamental signal rejection better than 12 dB. To the best of our knowledge, this is the first demonstration of distributed doubler using the high-pass drain line topology.