ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.     

Sixty years of dislocations

It is well-known that with the appearance of three independent papers by Taylor, Polanyi and Orowan in the year 1934, the concept of crystal dislocations was born. Since then, dislocation theory has had many spectacular successes. It is quite appropriate therefore to be aware of the state of development of this exciting subject, sixty years after its discovery. A flavour for the vast subject of the applications of dislocation mechanisms to real materials is presented by choosing three examples, one each, drawn from metallurgy, physics and electronics. The topic of ‘Strength of metals and alloys’ is the first one, as this is also the author’s area of research. The phenomenon of solidification and crystal growth forms the next topic, especially in view of the seminal contributions made by A R Verma and his school from India. Dislocations play a useful role in the strengthening of solids, but how influential are they in affecting the performance of modern semiconductor devices? In the third example, the interesting and painstaking work done to settle this question is reviewed. Can we regard carbon fibre as thetransistor of dislocation theory? How shall we understand the long-established effects such as corrosion-fatigue, superplasticity and shape memory as well as the electrochemical and electro-mechanical properties of dislocations in semiconductor and non-metallic crystals? Answers to these questions belong to the realms of the future developments in dislocations. The talk is concluded with a discussion of these topics.     

Understanding of the concept of numerically "less" by bottlenose dolphins (Tursiops truncatus).

In 2 experiments, bottlenose dolphins (Tursiops truncatus) judged the ordinal relationship between novel numerosities. The dolphins were first trained to choose the exemplar with the fewer number of items when presented with just a few specific comparisons (e.g., 2 vs. 6, 1 vs. 3, and 3 vs. 7). Generalization of this rule was then tested by presenting the dolphins with all possible pairwise comparisons between 1 and 8. The dolphins chose the exemplar with the fewer number of items at levels far above chance, showing that they could recognize and represent numerosities on an ordinal scale. Their pattern of errors was consistent with the idea of an underlying analog magnitude representation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reactive Power Compensation Technologies: State-of-the-Art Review

This paper presents an overview of the state of the art in reactive power compensation technologies. The principles of operation, design characteristics and application examples of Var compensators implemented with thyristors and self-commutated converters are presented. Static Var generators are used to improve voltage regulation, stability, and power factor in ac transmission and distribution systems. Examples obtained from relevant applications describing the use of reactive power compensators implemented with new static Var technologies are also described.     

Successful Aging

This issue's Works in Progress department presents six abstracts for projects that are developing interesting solutions to the elderly's quality of life challenges. The first two abstracts discuss projects that will help provide the elderly with freedom and independence by instrumenting their environments with supportive technology. The next two abstracts discuss projects building specialized user interfaces for addressing some of the challenges associated with aging, such as vision impairment. The final two abstracts present projects that will aid independence for the elderly by providing remote monitoring and assistance.     

Benzoquinones, a homoisoflavanone and other constitutents from Polygonatum alte-lobatum

From the rhizomes of Polygonatum alte-lobatum, two new homologous series of 1,4-benzoquinones, polygonaquinones A and B, a novel homoisoflavanone, a new gentrogenin glycoside and 13 known compounds were isolated and characterized. The structures of the new compounds were determined as two homologous series of three 2,5-dihydroxy-3-methyl-6-alkyl-1,4-benzoquinones and three 2-hydroxy-3-methyl-6-alkyl-1,4-benzoquinones, with chain lengths C21 to C23, and 4',5,7-trihydroxy-6,8-dimethylhomoisoflavanone and gentrogenin 3-O-beta-D-glucopyranosyl(1-->2)-[beta-D-xylopyranosyl(1-->3)] -beta-D-glucopyranosyl(1-->4)-beta-D-galactopyranoside.     

Transition metal joints for steam generators—An overview

The transition metal joint (TMJ) between an austenitic stainless steel and a chromium-molybdenum (Cr-Mo) ferritic steel used widely in steam generators of power plants has for a long time presented problems relating to premature failures in service. The direct (bimetallic) TMJ presently in use is designed for a service life of about 200,000 h; but such TMJs with iron-base weld metals have been failing in service within about one-third of their design lifetime, while their counterparts with nickel-base weld metals fail within about one-half of their design lifetime. The causes for such premature service failures of these TMJs are discussed in detail, leading to the development of improved TMJs. One of the improved TMJs with a trimetallic configuration of austenitic stainless steel/Alloy 800/Cr-Mo ferritic steel is discussed in detail, covering its development, characterisation and evaluation. Accelerated performance tests in the laboratory have indicated a four-fold improvement in the service life of the TMJ with this trimetallic configuration compared to the bimetallic configuration. The metallurgical details of these studies are also discussed in this paper.     

Plasminogen activator inhibitor-1 secretion of endothelial cells increases fibrinolytic resistance of an in vitro fibrin clot: evidence for a key role of endothelial cells in thrombolytic resistance

Time-dependent thrombolytic resistance is a critical problem in thrombolytic therapy for acute myocardial infarction. Platelets have been regarded as the main source of plasminogen activator inhibitor-1 (PAI-1) found in occlusive platelet-rich clots. However, endothelial cells are also known to influence the fibrinolytic capacity of blood vessels, but their ability to actively mediate time-dependent thrombolytic resistance has not been fully established. We will show that, in vitro, tumor necrosis factor-alpha-stimulated endothelial cells secrete large amounts of PAI-1 over a period of hours, which then binds to fibrin and protects the clot from tissue plasminogen activator-induced fibrinolysis. In vivo, endothelial cells covering atherosclerotic plaques are influenced by cytokines synthesized by plaque cells. Therefore, we propose that continuous activation of endothelial cells in atherosclerotic blood vessels, followed by elevated PAI-1 secretion and storage of active PAI-1 in the fibrin matrix, leads to clot stabilization. This scenario makes endothelial cells a major factor in time-dependent thrombolytic resistance.