Endothelin receptor antagonists: effect of serum albumin on potency and comparison of pharmacological characteristics

Endothelins (ETs) are 21-amino acid peptides that bind to membrane receptors to initiate pathophysiological effects. Two types of ET receptors, ETA and ETB, have been identified. Various ET receptor antagonists are being developed as therapeutic agents. This report examines the effects of bovine serum albumin (BSA) on the potency of ET receptor antagonists and compares five ET receptor antagonists. Competition studies show that in the absence of BSA, A-127722 and L-749329 inhibited ET-1 binding to ETA receptor with the same IC50 value of 0.09 nM. Addition of increasing concentrations of BSA incrementally decreased the potency of the antagonists: in the presence of 5% BSA, the IC50 values increased to 4.3 and 820 nM, respectively. Similarly, addition of BSA decreased the potency of antagonists in inhibiting ET-1-stimulated phosphatidylinositol hydrolysis. These results suggest that serum albumin has profound effects on the potencies of ET receptor antagonists. FR139317, PD-156707, L-749329, Ro-47-0203 and A-127722 were then selected for direct comparison under identical experimental conditions with 0.2% BSA. The potency of antagonists was assessed by binding studies for the determination of IC50 and Ki values and by ET-1-stimulated phosphatidylinositol hydrolysis and arachidonic acid release for the determination of IC50 and pA2 values. All five antagonists inhibited ET binding and the biological effects exerted by ET in a competitive mode. The Ki values for A-127722, PD-156707, FR139317, Ro-47-0203 and L-749329 for the ETA receptor were 0.07, 0.38, 0.80, 3.67 and 33.6 nM, respectively. A similar hierarchy was revealed by the functional assays. Our results suggest that the rank order of potency of the antagonists is A-127722 > or = PD-156707 > or = FR139317 > Ro-47-0203 > L-749329.     

Vena contracta suppression in dilute polymer solutions

Very small amounts of high molecular weight polymers were found to eliminate vena contracta formation in flow through a circular orifice. This effect was reflected in the decreased efflux time for drainage between two fixed levels in a tank, reductions up to 30% being obtained. Aqueous solutions of seven commercially available polymers were studied, consisting of a poly(acrylic acid), two polyacrylamides of different degrees of hydrolysis, and four poly(ethylene oxides) of widely differing molecular weights. The poly(acrylic acid) and two highest molecular weight poly(ethylene oxides) each caused a sudden drop in efflux time at a “critical concentration”, which was 2, 50, and 90 wppm, respectively, for these three polymers. An explanation of this phenomenon in terms of the high Deborah number flow field existing near the orifice edge is advanced. In the case of the polyacrylamide solutions, a very gradual reduction in efflux time with increasing polymer concentration was observed, beginning at about 3 wppm. Coincident with this was the formation of a wine-glass stem or converging flow field upstream of the orifice. Such a flow field was not observed for the other solutions. It is suggested that vena contracta inhibition with polyacrylamide is simply a manifestation of solution die swell. The reason for the differing efflux time behavior between the various polymers is not known and represents a challenging problem for further study.     

Ultrasonic Sol/Gel Processing of Aluminoborosilicate Glass and Its Composite with Carbon Fiber Reinforcement

An ultrasonic sol/gel technique has been used to process aluminoborosilicate glass and its composite with carbon fiber reinforcement. In this new technique, ultrasonic energy is used in place of alcohol solvent. Gel time is easily controlled by varying the amount of ultrasonic energy and the resulting gel also exhibits less shrinkage during the densification process. The sonogel-based composite has lower flexural strengths than the alcogel and has close values between the measured moduli, while still retaining the same fracture toughness. Micromechanical analysis produces higher values; however, ill is suspected that the in situ modulus of matrix is lower than the value used in the analysis.     

An AlGaAs-GaAs dual-wavelength photodetector with 500 Å resolution

An Au-(N)Al_0.07Ga_0.93As-(n)GaAs Schottky barrier dual-wavelength photodetector with 500 Å resolution has been developed. By varying the reverse bias, the photothreshold of the detector can be changed from 0.82 to 0.87 μm. The diode can thus be applied to demultiplex two optical signals with respective wavelengths of 0.8 and 0.85 μm. This provides a useful detector for use in a dual-channel optical communication system. The principle is based on the band readjustment effect which is due to the interaction of the closely-spaced Au-AlGaAs Schottky barrier and the AlGaAs-GaAs heterojunction.     

A rapid and sensitive method for determination of theophylline in plasma and saliva by high pressure liquid chromatography

A fast and sensitive high pressure liquid chromatographic method for the monitoring of theophylline concentrations in plasma or saliva was developed. Each sample requires only about 15 minutes for the completion of the assay after receiving the plasma or saliva sample. Only 0.1 ml of sample is required, and concentrations as low as 1 mcg/ml can be accurately measured.     

Decomposition of 2-naphthalenesulfonate in electroplating solution by ozonation with UV radiation

This study investigates the ozonation of 2-naphthalenesulfonate (2-NS) combined with UV radiation in the electroplating solution. 2-NS is commonly used as a brightening and stabilization agent in the electroplating solution. Semibatch ozonation experiments were conducted under various reaction conditions to study the effects of ozone dosage and UV radiation on the oxidation of 2-NS. The concentrations of 2-NS were analyzed at specified time intervals to elucidate the decomposition of 2-NS. Total organic carbon (TOC) is chosen as a mineralization index of the ozonation of 2-NS. In addition, values of pH and oxidation reduction potential were continuously measured in the course of experiments. As a result, the nearly complete mineralization of 2-NS via the ozonation treatment can be achieved. The mineralization of 2-NS is found accelerated by the introduction of UV radiation and has a distinct relationship with the consumption of applied ozone. These results can provide useful information for the proper removal of 2-NS in the electroplating solution by the ozonation with UV radiation.     

Evaluating phenanthrene sorption on various wood chars

A certain amount of wood char or soot in a soil or sediment sample may cause the sorption of organic compounds to deviate significantly from the linear partitioning commonly observed with soil organic matter (SOM). Laboratory produced and field wood chars have been obtained and analyzed for their sorption isotherms of a model solute (phenanthrene) from water solution. The uptake capacities and nonlinear sorption effects with the laboratory wood chars are similar to those with the field wood chars. For phenanthrene aqueous concentrations of 1 microg l(-1), the organic carbon-normalized sorption coefficients (log K(oc)) ranging from 5.0 to 6.4 for field chars and 5.4-7.3 for laboratory wood chars, which is consistent with literature values (5.6-7.1). Data with artificial chars suggest that the variation in sorption potential can be attributed to heating temperature and starting material, and both the quantity and heterogeneity of surface-area impacts the sorption capacity. These results thus help to corroborate and explain the range of logK(oc) values reported in previous research for aquifer materials containing wood chars.     

Vortex flow of dilute polymer solutions

It has been observed that very d longchain polymers which are effective in turbulent drag reduction inhibit the formation of a vortex or air core as water drains from a tank. This paper considers the fluid mechanical velocity profile measurements have been performed. There appear to be at least two distinct mechanisms for the vortex inhibition—one involving the viscosity enhancement caused by polymer addition, and the other related to the viscoelastic properties of the polymer solutions. This second mechanism is shown to arise due to the generation of high normal stresses as the air core begins to form. The very close correlation between vortex inhibition and turbulent drag reduction suggests that normal stresses may also play an important role in this latter phenomenon.     

On-line measurement-based model parameter estimation forsynchronous generators: solution algorithm and numerical studies

In this paper, a sixth-order synchronous generator model identification technique from online measurements is considered. An algorithm is devised to identify the generator model. A constrained conjugate gradient method is incorporated into the algorithm to guarantee rapid convergence to the final solution. Using the algorithm, a complete generator model is derived from online measurements recorded by a plant transient recording system during a system disturbance. In addition, the algorithm does not greatly rely upon the accuracy of the initial estimates, allowing the initial estimates to deviate reasonably far from the true parameters. Detailed numerical studies of the Taipower system using raw and filtered data are included