A noncompetitive peptide inhibitor of the nicotinic acetylcholine receptor from Conus purpurascens venom

A paralytic peptide, psi-conotoxin Piiie has been purified and characterized from Conus purpurascens venom. Electrophysiological studies indicate that the peptide inhibits the nicotinic acetylcholine receptor (nAChR). However, the peptide does not block the binding of alpha-bungarotoxin, a competitive nAChR antagonist. Thus, psi-conotoxin Piiie appears to inhibit the receptor at a site other than the acetylcholine-binding site. As ascertained by sequence analysis, mass spectrometry, and chemical synthesis, the peptide has the following covalent structure: HOOCCLYGKCRRYOGCSSASCCQR* (O = 4-trans hydroxyproline; * indicates an amidated C-terminus). The disulfide connectivity of the toxin is unrelated to the alpha- or the alphaA-conotoxins, the Conus peptide families that are competitive inhibitors of the nAChR, but shows homology to the mu-conotoxins (which are Na+ channel blockers).     

A magnetic resonance imaging study of planum temporale asymmetry in men with developmental dyslexia

The influence of ionic strength and composition on the binding and inhibition of human leukocyte elastase by glycosaminoglycans with variable degree and position of sulfation was investigated. The kinetic mechanism of inhibition had a hyperbolic, mixed-type character with a competitive component that was promoted by low ionic strength, reduced by phosphate ions, and which also depended on the substrate and glycosaminoglycan structure. Enzyme binding was a cooperative phenomenon that varied with ionic strength and composition. The inhibition patterns correlated with the cationic character of elastase and with the distribution of arginines on its molecular surface, most notably with residues located in the vicinity of the substrate binding region. The order of affinity for elastase binding was chondroitin 4-sulfate < chondroitin 6-sulfate < dermatan sulfate, iduronate-containing derivatives being superior with respect to the glucuronate-containing counterparts. Additional sulfation at both the 4- and 6- positions or at the N- and 4-positions of the N-acetylgalactosamine moiety decidedly improved the inhibitory efficiency. The results highlight a fundamental physiological role of enzyme-glycosaminoglycan interactions. In the azurophil granule of the human polymorphonuclear neutrophil, elastase and other enzymes are bound to a matrix of chondroitin 4-sulfate because this is the only glycosaminoglycan that simultaneously offers good binding for enzyme compartmentalization together with prompt release from the bound state at the onset of phagocytosis.     

An Experimental Investigation into the Feed Rate Capacity of Rotary Valve and Blow Tank Feeders

Industry widely uses rotary valves and blow tanks for the pneumatic conveying of products, each having their pros and cons depending on the specific application. This article shows the differing results obtained when low-velocity conveying a product through a common pipeline using both a drop-through rotary valve and a bottom-discharge blow tank feeder. A number of issues arise in the rotary valve system, the main one being rotary valve air leakage. A blow tank system, on the other hand, does not leak, as it is an enclosed system. The experimental results show dramatic differences in product throughput. Further exploration leads to a novel modification being made to the rotary valve system in an attempt to increase its capacity. The result of this modification shows a slight increase in output tonnage, but still significantly less than that obtained from the blow tank.     

P#: a concurrent Prolog for the .NET framework

We discuss P#, our implementation of a tool that allows interoperation between a concurrent superset of the Prolog programming language and C#. This enables Prolog to be used as a native implementation language for Microsoft's .NET platform. P# compiles a linear logic extension of Prolog to C# source code. We can thus create C# objects from Prolog and use C#'s graphical, networking and other libraries. We add language constructs on the Prolog side that allow concurrent Prolog code to be written. A primitive predicate is provided that evaluates a Prolog structure on a newly forked thread. Communication between threads is based on the unification of variables contained in such a structure. It is also possible for threads to communicate through a globally accessible table. All of the new features are available to the programmer through new built-in Prolog predicates. We discuss two software engineering tools implemented using P#. Copyright © 2004 John Wiley & Sons, Ltd.