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.     

Stabilization of bioethanol recovery with silicone rubber‐coated ethanol‐permselective silicalite membranes by controlling the pH of acidic feed solution

In order to produce highly concentrated bioethanol by pervaporation using an ethanol‐permselective silicalite membrane, techniques to suppress adsorption of succinic acid, which is a chief by‐product of ethanol fermentation and causes the deterioration in pervaporation performance, onto the silicalite crystals was investigated. The amount adsorbed increased as the pH of the aqueous succinic acid solution decreased. The pervaporation performance also decreased with decreasing pH when the ternary mixtures of ethanol/water/succinic acid were separated. Using silicalite membranes individually coated with two types of silicone rubber, pervaporation performance was significantly improved in the pH range of 5 to 7, when compared with that of non‐coated silicalite membranes in ternary mixtures of ethanol/water/succinic acid. Moreover, when using a silicalite membrane double‐coated with the two types of silicone rubber, pervaporation performance was stabilized at lower pH values. In the separation of bioethanol by pervaporation using the double‐coated silicalite membrane, removal of accumulated substances having an ultraviolet absorption maximum at approximately 260 nm from the fermentation broth proved to be vital for efficient pervaporation. Copyright © 2005 Society of Chemical Industry     

A novel dynamic survivable routing in WDM optical networks with/without sparse wavelength conversion

In this paper, we study the dynamic survivable routing problem, both in optical networks without wavelength conversion and in optical networks with sparse wavelength conversion, and propose a novel hybrid algorithm for it based on the combination of mobile agents technique and genetic algorithms (GA). By keeping a suitable number of mobile agents in the network to cooperatively explore the network states and continuously report cycles (that are formed by two disjoint-link routes) into the routing tables, our new hybrid algorithm can promptly determine the first population of cycles for a new request based on the routing table of its source node, without the time consuming process associated with current GA-based lightpath protection schemes. We further improve the performance of our algorithm by introducing a more advanced fitness function that is suitable for both the above networks. Extensive simulation studies on the ns-2 network simulator show that our hybrid algorithm achieves a significantly lower blocking probability than the conventional survivable routing algorithms for all the cases we studied.     

Enhancement mode InP MISFET's with sulfide passivation andphoto-CVD grown P3N5 gate insulators

High performance enhancement mode InP MISFET's have been successfully fabricated by using the sulfide passivation for lower interface states and with photo-CVD grown P₃N₅ film used as gate insulator. The MISFET's thus fabricated exhibited exhibited pinch-off behavior with essentially no hysteresis. Furthermore the device showed a superior stability of drain current. Specifically under the gate bias of 2 V for 10⁴ seconds the room temperature drain current was shown to reduce from the initial value merely by 2.9% at the drain voltage of 4 V. The effective electron mobility and extrinsic transconductance are found to be about 2300 cm ²/V·s and 2.7 mS/mm, respectively. The capacitance-voltage characteristics of the sulfide passivated InP MIS diodes show little hysteresis and the minimum density of interface trap states as low as 2.6×10¹⁴/cm² eV has been attained     

Numerical analyses of high‐beta spherical tokamaks with varied elongation

The effect of plasma elongation on the second‐stable spherical tokamak (ST) was numerically studied using the experimentally measured pressure and current profiles of ultrahigh‐beta STs. The maximum beta of ST over 50% was obtained in the TS‐3 ST/CT experiment by applying an external toroidal field to an FRC. It was found that the marginal beta for the ballooning instability increased with the plasma elongation κ of ST. The elongated STs with κ > 2 have the magnetic shear (S)–pressure gradient (α) profiles located in the second‐stable regime for the ballooning mode and the stability margin increased with κ. The close relation between the absolute minimum‐B profile and the second stability was documented. The effect of elongation on maximum beta was observed to saturate when κ exceed 3, indicating that the optimized elongation for high‐beta STs is located around 2 < κ < 3. © 2006 Wiley Periodicals, Inc. Electr Eng Jpn, 155(4): 1–6, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20132     

Suppression of photo-induced dilation in cyanide treated hydrogenated amorphous silicon films

Effects of cyanide (CN) treatment with hydrogenated amorphous silicon (a-Si:H) films have been investigated. The decrease of ΔV/V was observed in cyanide treated a-Si:H films and the successive thermal annealing at 200°C after CN treatment induced the further reduction of the ΔV/V. XPS spectra show the indirect evidence that the cyanide species is present within 10 nm from the hydrogenated amorphous silicon surface. The results of CN treatment with a-Si:H solar cells are demonstrated.