Characterization of AT4 receptor from bovine aortic endothelium with photosensitive analogues of angiotensin IV

Newly developed photosensitive analogues of AngIV were used to characterize the AT4 receptor of bovine aortic endothelial cells. The photoactivatable AngIV analogues [N3-Phe6]AngIV and [Bpa6]AngIV displayed high affinities for AT4 receptor, with IC50's of 3.7 +/- 0.3 and 19.1 +/- 3.5 nM, respectively. The radioiodinated ligands showed a good efficiency of photoaffinity labeling demonstrated by high proportions (60-75%) of acid-resistant binding. Covalently labeled receptor was solubilized under reducing or nonreducing conditions and subjected to SDS-PAGE. Under nonreducing conditions, autoradiographies revealed a major band of Mr 186 +/- 2 kDa and a minor band of Mr 241 +/- 6 kDa. The labeling of these bands was completely abolished in the presence of 10 microM AngIV. Under reducing conditions, only the low Mr 186 kDa band was revealed. After endoglycosidase digestion with an enzyme that cleaves N-linked saccharides, the Mr of the denatured AT4 receptor was decreased by 31% to a value of 129 +/- 10 kDa. Kinetic studies revealed a stepwise process of AT4 receptor deglycosylation by endoglycosidase F, suggesting at least two different sites of N-linked saccharides. Mild trypsin treatment of photolabeled endothelial cell membranes released a large fragment of Mr 177 +/- 3 kDa which accounts for about 95% of the whole receptor molecular mass. These results demonstrate that [N3-Phe6]AngIV and [Bpa6]AngIV are very efficient tools for selective photoaffinity labeling of AT4 receptor. We have shown that AT4 receptor is a 186 kDa integral membrane glycoprotein with a very large extracellular domain. These properties are consistent with those of a growth factor or cytokine receptor.     

A quantitative study of fault tolerance, noise immunity, and generalization ability of MLPs

An analysis of the influence of weight and input perturbations in a multilayer perceptron (MLP) is made in this article. Quantitative measurements of fault tolerance, noise immunity, and generalization ability are provided. From the expressions obtained, it is possible to justify some previously reported conjectures and experimentally obtained results (e.g., the influence of weight magnitudes, the relation between training with noise and the generalization ability, the relation between fault tolerance and the generalization ability). The measurements introduced here are explicitly related to the mean squared error degradation in the presence of perturbations, thus constituting a selection criterion between different alternatives of weight configurations. Moreover, they allow us to predict the degradation of the learning performance of an MLP when its weights or inputs are deviated from their nominal values and thus, the behavior of a physical implementation can be evaluated before the weights are mapped on it according to its accuracy.     

Pompes de chaleur à transferts thermiques sans auxiliaires, à convection naturelle et rayonnementHeat pumps operating without power for auxiliaries by using natural convection and radiation heat transfer

With many conventional heat pump systems the energy absorbed by auxiliary equipment (fans, defrosters, pumps) can be higher than the power used by the compressor. For example, with a particular air-air heat pump system the annual energy consumption of the compressor and its crankcase heater is 11 240 kWh, whilst 21 501 kWh of energy are consumed by auxiliary fans, the defrost unit, back-up heating and system heat losses. Some savings can be made by monitoring the interior unit fan to correspond to the running time of the compressor or by increasing the size of the heat pump in order to reduce back-up heating, but the latter solution has proved to be costly.Laboratory experiments since 1976 have been to reduce power consumption of auxiliaries, particularly air-air and air-water systems, by using a solar collector as the heat pump evaporator. The collector is made up of flat plates oriented in such a manner as to receive direct solar radiation, with both faces of the plates absorbing energy from the surrounding air by natural convection. The faces of the plates exposed to solar radiation are preferably painted black, but other colours with a low coefficient of reflection (eg brown, brick red, dark green, etc.) can be used if the evaporator-collector is to be architecturally pleasing. Glazing is not necessary, as is usually the case with solar panels. The collector-evaporator plates, and associated piping, are precharged with refrigerant and ready for connection to the heat pump circuit.A heat pump equipped with this collector-evaporator will provide an annual energy saving of 30% as compared to a standard air—water system. Additional benefits are no defrosting cycles, simplified installation, greater operational reliability, and an increased system COP. A table sets out the performance parameters of this system to show the incidence of back-up solar energy during the months of lesser solar radiation, ie outside the months of June to September, eg the COP during daylight hours (a minimum of about 7 h in December, to a minimum of 14 h in May) averages out at 3.89, and 3.27 during nocturnal hours.The article also describes a water heating system (200 and 300 I) using this collector-evaporator, an air-air heat pump with static (no forced ventilation) heat exchangers, and an air-water system using a static evaporator which will provide a 25% energy saving over its conventional counterpart.     

Myocardial color scan with 43K in ischemic heart disease

The value of myocardial scanning with 43K was assessed in 64 consecutive patients undergoing coronary arteriography, and in five young volunteers. Myocardial scans at rest detected only 16 of the 35 transmural infarcts documented on electrocardiograms, 11 of 11 anterior infarcts and five of 24 in other sites. Myocardial scans were obtained immediately after a graded exercise test in the five normal volunteers, in nine patients with normal coronary arteriograms and in 25 patients with atherosclerotic narrowing greater than 75% involving the left anterior descending artery, with or without disease of other coronary vessels. All patients with normal coronary arteriograms had normal myocardial scans. A regional perfusion deficit was observed after exercise in all six patients with single vessel disease, but in only 11 of the 19 patients with disease involving two or three vessels. Although the technique was specific, it lacked sensitivity, due mostly to poor resolution and the location of the disease.     

Effect of glutamine supplementation on splanchnic metabolism in lactating dairy cows

The suggestion that glutamine (Gln) might become conditionally essential postpartum in dairy cows has been examined through increased postruminal supply of Gln. Net nutrient flux through the splanchnic tissues and mammary gland was measured in 7 multiparous Holstein cows receiving abomasal infusions of water or 300 g/d of Gln for 21 d in a crossover design. Milk yield increased significantly (by 3%) in response to Gln supplementation, but the 2.4% increase in milk protein yield was not statistically significant. Glutamine treatment had no effect on portal or hepatic venous blood flows. Net portal appearance of Gln and Glu was increased by Gln supplementation, accounting for 83% of the infused dose with, therefore, only limited amounts available to provide additional energy to fuel metabolism of the portal-drained viscera. The extra net portal appearance of Gln was offset, however, by a corresponding increase in hepatic removal such that net Gln splanchnic release was not different between treatments. Nonetheless, the Gln treatment resulted in a 43% increase in plasma Gln concentration. Infusions of Gln did not affect splanchnic flux of other nonessential amino acids or of essential amino acids. Glutamine supplementation increased plasma urea-N concentration and tended to increase net hepatic urea flux, with a numerical increase in liver hepatic O₂ consumption. There were no effects on glucose in terms of plasma concentration, net portal appearance, net liver release, or postliver supply, suggesting that Gln supplementation had no sparing effect on glucose metabolism. Furthermore, mammary uptake of glucose and amino acids, including Gln, was not affected by Gln supplementation. In conclusion, this study did not support the hypothesis that supplemental Gln would reduce glucose utilization across the gut or increase liver gluconeogenesis or mammary glutamine uptake to increase milk protein synthesis.     

Modeling and measurement approaches for electrostatic discharge in semiconductor devices and ICs: an overview

Electrostatic charges can be generated everywhere. When they are discharged through semiconductor devices and integrated circuits, an event called an electrostatic discharge (ESD), failure of electronics systems using these devices and ICs can occur. This paper first gives an overview of the ESD sources and models. Then the emphasis is placed on the modeling and measurements of the most commonly used of these models called the human body model (HBM). Various HBM protection circuits are examined to look at ways of preventing ICs from being damaged should ESD events occur. The issue of HBM measurements is also addressed so that the rapid transient associated with this ESD model can be accurately measured and characterized.     

The high affinity state of inositol 1,4,5-trisphosphate receptor is a functional state

Inositol 1,4,5-trisphosphate (InsP3) is a second messenger responsible for the rapid and discontinuous release of Ca2+ from intracellular stores. In this study, the effects of the sulfhydryl reagent thimerosal were investigated on Ca2+ mobilization and on InsP3 binding. Thimerosal was shown to release Ca2+, in a dose-dependent manner, with an EC50 of 135.8 +/- 5.2 microM, from bovine adrenal cortex microsomes. Thimerosal-induced Ca2+ release was not prevented by heparin (250 micrograms/ml), ruling out a participation of InsP3 receptor in that effect. The slow rate of thimerosal-induced Ca2+ release rather suggested an inhibition of microsomal Ca2+ ATPase. At submaximal concentration, thimerosal (100 microM) was also shown to potentiate the release of Ca2+ induced by InsP3. Dose-response experiments revealed that thimerosal enhanced the apparent affinity of InsP3 by a factor 2.21 +/- 0.28, without modifying the maximal amount of Ca2+ released by InsP3. Thimerosal also enhanced, in a dose-dependent manner, [3H]InsP3 binding to adrenal cortex microsomes (EC50 = 43.3 +/- 7.6 microM). A similar effect was also observed on [3H]InsP3 binding to solubilized receptors, suggesting a direct modification of the receptor protein by thimerosal. The effects of thimerosal on Ca2+ release and [3H]InsP3 binding were abolished in the presence of the reducing agent dithiothreitol (1 mM), suggesting a modification by thimerosal of specific thiol groups on these microsomal proteins. Scatchard analysis revealed that thimerosal (100 microM) increased InsP3 receptor affinity by 1.87 +/- 0.26-fold. Kinetic analysis indicated that this increased affinity was due to an enhancement of InsP3 association rate constant. The concomitant increases of binding affinity and Ca2+ releasing potency suggest that the high affinity state of InsP3 receptor is a functional state.     

The programme of quality assurance of the EORTC radiotherapy group. A historical overview

Decreased activity of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the catabolism of cholesterol to bile acids, is known to result in increased biliary cholesterol concentration and supersaturation of bile. Supersaturation of bile by cholesterol is a necessary condition for cholesterol gallstone formation. In guinea pigs, the hepatic concentration of ascorbic acid affects the catabolism of cholesterol: hypovitaminosis C reduces cholesterol 7 alpha-hydroxylase activity. Cholesterol gallstones are frequently found in ascorbic acid-deficient guinea pigs. Risk factors for cholesterol gallstones in humans include obesity, aging, estrogen treatment, pregnancy and diabetes. Plasma ascorbic acid levels are reduced in these groups. Vegetarian diets, which typically have high ascorbic acid contents, protect against gallstones. Since ascorbic acid effects the rate-limiting step in the catabolism of cholesterol in the guinea pig and many human risk groups for cholesterol gallstones are associated with reduced ascorbic acid levels, ascorbic acid may play a contributory role in human gallbladder disease.     

Cellulose acetate structural foam

Structural foams of cellulose acetate were prepared at densities down to 1.01. Decreasing density produced decreasing cell size, decreasing flexural modulus, and surprisingly, increasing impact strength.