Modification of the calcium and calmodulin sensitivity of the type I adenylyl cyclase by mutagenesis of its calmodulin binding domain

The type I adenylyl cyclase is directly stimulated by Ca2+ and calmodulin in vitro, and the enzyme is also stimulated by increases in intracellular Ca2+ in vivo. Ca2+ stimulation of the enzyme in vivo may be due to direct interactions of the enzyme with Ca2+ and calmodulin or to an indirect mechanism involving stimulation of the enzyme by Ca(2+)-activated protein kinases. In this study, we have made several point mutations within the calmodulin binding domain to determine if the Ca2+ sensitivity of the enzyme can be modified by mutagenesis. The catalytic activities of the mutant enzymes were comparable to wild type type I adenylyl cyclase. Substitution of Cys-507 with Ser-507 did not have significant effects on the calmodulin or Ca2+ sensitivity of the enzyme. However, replacement of Lys-504 with Asp caused a 4-fold decrease in sensitivity to Ca2+. Ca2+ and calmodulin stimulation were abolished by substitution of Phe-503 with Arg-503. Stimulation of type I adenylyl cyclase activity in vivo by intracellular Ca2+ was also greatly diminished with the Arg-503 mutant indicating that Ca2+ stimulation of the enzyme in vivo is due primarily to direct interactions with calmodulin and Ca2+. These data demonstrate that the Ca2+ sensitivity of this enzyme can be modulated by point mutagenesis within the putative calmodulin binding domain and indicate that the enzyme can be directly regulated by Ca2+ and calmodulin in vivo.     

A 150 MHz 0.6 μm BiCMOS superscalar microprocessor

An implementation of the Pentium microprocessor architecture in 0.6 μm BiCMOS technology is described. Power dissipation is reduced and performance is enhanced over the previous generation. Processor features, implementation technology, and circuit techniques are discussed. An internal clock rate of 150 MHz is achieved at 3.7 V and -55°C     

The effects of impact ionization on the operation of neighboringdevices and circuits

This paper examines the detrimental effects of excess majority carriers and photons induced by impact ionization on the operation of neighboring pn junctions, bipolar transistors, MOS transistors, and circuits. The experimental results show that in addition to an increase in the substrate surface potential due to the excess majority carriers, photons can lower the barrier of a pn junction and, as a consequence, shift the Gummel plot of an npn bipolar transistor. As for the neighboring circuits, an example in which the speed of an NMOS ring oscillator is retarded by impact ionization in a neighboring NMOS transistor is presented     

Fuzzy rule interpolation for multidimensional input spaces in determining d50c of hydrocyclones

Fuzzy rule-based systems have been very popular in many engineering applications. In mineral engineering, fuzzy rules are normally constructed using some fuzzy rule extraction techniques to establish the determination model in predicting the d50c of hydrocyclones. However, when generating fuzzy rules from the available information, it may result in a sparse fuzzy rule base. The use of more than one input variable is also common in hydrocyclone data analysis. This paper examines the application of fuzzy interpolation to resolve the problems using sparse fuzzy rule bases, and to perform analysis of fuzzy interpolation in multidimensional input spaces.     

Non-peptidic HIV protease inhibitors: C2-symmetry-based design of bis-sulfonamide dihydropyrones

Potent, non-peptidic, dihydropyrone sulfonamide HIV protease inhibitors have been previously described. Crystallographic analysis of dihydropyrone sulfonamide inhibitor/HIV protease complexes suggested incorporation of a second, C2 symmetry-related sulfonamide group. Selected bis-sulfonamide dihydropyrone analogues display high HIV protease inhibitory activity.     

An antinociceptive effect of the intraperitoneal injection of nifedipine in rats, measured by tail-flick test

The tail-flick (TF) technique was used to assess the antinociceptive properties of nifedipine (NIF) given intraperitoneally (i.p.). First, the most suitable intensity of the noxious stimulus (temperature of the bulb) has been ascertained and used in the main study. Male Sprague-Dawley rats received NIF, dissolved in dimethyl sulfoxide (DMSO) at the doses of 0.0, 0.5, 2, 5, 10 and 15 mg/kg, or control with no injection. For the main study, the noxious stimulus was limited to 15 sec (cut-off time) and TF latencies were recorded up to 120 min. The antinociceptive response was expressed as the area under the curve for each rat and analyzed by one-way ANOVA. The antinociceptive response to the lower doses of NIF (0.5 and 2 mg/kg) did not differ from control (no injection) and DMSO alone. Significance was found at 5, 10 and 15 mg NIF with no difference among the doses. However, there was an increasing tendency of the mean values from 0.5 to 15 mg NIF resulting in a positive correlation. The correlation coefficient was 0.32483 (p = 0.015) and regression equation Y = (19.37) x dose + 1320. Our data suggest that spinal mechanisms are involved in NIF-induced antinociception.