Antilipid a monoclonal antibody HA-1A: immune complex clearance of endotoxin reduces TNF-alpha, IL-1 beta and IL-6 production

When the projecting point of saphenous nerve in second somatosensory cortex (S II) of cat was stimulated, the evoked potentials elicited by C-fiber inputs of saphenous nerve recorded in the primary somatosensory cortex (C-CEP) might be either inhibited or facilited according to whether the superficial and/or the deeper layer of the cortex was stimulated. The inhibition was expressed as a decrease of amplitude and prolongation of latency of C-CEP; while the facilitation, as an increase of amplitude and duration of C-CEP. When the superfaicial layer of S II was stimulated by weaker current, both inhibitory and facilitatory effects could be observed, but only inhibitory effect was observed, when the deep layer was stimulated. With the same intensity of stimulation, inhibitory effect was more pronounced when the deep layer rather than the superficial layer was stimulated. It is suggested that S II may play a role in the modulation of C-CEP of S I.     

Multiple solution conformations of the integrin-binding cyclic pentapeptide cyclo(-Ser-D-Leu-Asp-Val-Pro-). Analysis of the (phi, psi) space available to cyclic pentapeptides

The aqueous solution structure of the cyclic pentapeptide cyclo(-Ser-D-Leu-Asp-Val-Pro-) has been determined by two-dimensional 1H-NMR spectroscopy, combined with a conformational search and distance-geometry calculations. As many as five conformers in slow exchange were observed, and the rate of interconversion between components was measured from the build-up rates of exchange peaks. NMR data allowed the structures of the two predominant conformers to be determined. The major component (66%) contained a cis-proline as part of a type-VIa2 beta-turn encompassing residues Asp-Val-cis-Pro-Ser. The second component (16%) contained only trans-amide bonds, and a type-VIII beta-turn formed by residues Val-Pro-Ser-D-Leu. These structures are discussed in relation to the (phi, psi), space available to the cyclic pentapeptide, determined by a conformational search, and in relation to previously published cyclic-pentapeptide structures. The molecule exhibits activity in a scintillation-proximity assay for the inhibition of the interaction between the integrin very-late antigen-4 (VLA-4; alpha 4 beta 1) and vascular-cell-adhesion molecule-1 (VCAM-1). The structure/activity relationship of the LDV sequence is discussed and related to the recently published X-ray structure of VCAM-1. The relevance of the work to the design of anti-inflammatory drugs is discussed.     

X-ray microtomography: Application to microstructure analysis of a cementitious material during leaching process

Leaching of cementitious materials leads to an increase in porosity, which has important consequences on transport and mechanical properties. The present study outlines the characterization of microstructural evolution in a mortar subjected to a chemical attack, by means of a powerful non-intrusive experimental method, namely synchrotron X-ray computed microtomography. This innovative method is used to measure the variation of porosity in a leached mortar. Having described the effects of leaching in mortar (influences on microstructure and on mechanical properties), we present the accelerated leaching process and the microtomographic analysis that have been used to monitor it. We then investigate the capacity of this method to quantify the evolution of porosity during the leaching process. The method is validated by comparison of the results obtained with data available in the literature.     

Visual insights into high-resolution earthquake Simulations.

This study focuses on the visualization of a series of large earthquake simulations collectively called TeraShake. The simulation series aims to assess the impact of San Andreas Fault earthquake scenarios in Southern California. We discuss the role of visualization in gaining scientific insight and aiding unexpected discoveries.     

Hybrid Approach for Addressing Uncertainty in Risk Assessments

Parameter uncertainty is a major aspect of the model-based estimation of the risk of human exposure to pollutants. The Monte Carlo method, which applies probability theory to address model parameter uncertainty, relies on a statistical representation of available information. In recent years, other uncertainty theories have been proposed as alternative approaches to address model parameter uncertainty in situations where available information is insufficient to identify statistically representative probability distributions, due in particular to data scarcity. The simplest such theory is possibility theory, which uses so-called fuzzy numbers to represent model parameter uncertainty. In practice, it may occur that certain model parameters can be reasonably represented by probability distributions, because there are sufficient data available to substantiate such distributions by statistical analysis, while others are better represented by fuzzy numbers (due to data scarcity). The question then arises as to how these two modes of representation of model parameter uncertainty can be combined for the purpose of estimating the risk of exposure. This paper proposes an approach (termed a hybrid approach) which combines Monte Carlo random sampling of probability distribution functions with fuzzy calculus. The approach is applied to a real case of estimation of human exposure, via vegetable consumption, to cadmium present in the surficial soils of an industrial site located in the north of France. The application illustrates the potential of the proposed approach, which allows the uncertainty affecting model parameters to be represented in a way that is consistent with the information at hand. Also, because the hybrid approach takes advantage of the “rich” information provided by probability distributions, while retaining the conservative character of fuzzy calculus, it is believed to hold value in terms of a “reasonable” application of the precautionary principle.     

Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors

Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABA(A) and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA rho1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.