Relationship between prion propensity and the rates of individual molecular steps of fibril assembly.

Peptides and proteins possess an inherent propensity to self-assemble into generic fibrillar nanostructures known as amyloid fibrils, some of which are involved in medical conditions such as Alzheimer disease. In certain cases, such structures can self-propagate in living systems as prions and transmit characteristic traits to the host organism. The mechanisms that allow certain amyloid species but not others to function as prions are not fully understood. Much progress in understanding the prion phenomenon has been achieved through the study of prions in yeast as this system has proved to be experimentally highly tractable; but quantitative understanding of the biophysics and kinetics of the assembly process has remained challenging. Here, we explore the assembly of two closely related homologues of the Ure2p protein from Saccharomyces cerevisiae and Saccharomyces paradoxus, and by using a combination of kinetic theory with solution and biosensor assays, we are able to compare the rates of the individual microscopic steps of prion fibril assembly. We find that for these proteins the fragmentation rate is encoded in the structure of the seed fibrils, whereas the elongation rate is principally determined by the nature of the soluble precursor protein. Our results further reveal that fibrils that elongate faster but fracture less frequently can lose their ability to propagate as prions. These findings illuminate the connections between the in vitro aggregation of proteins and the in vivo proliferation of prions, and provide a framework for the quantitative understanding of the parameters governing the behavior of amyloid fibrils in normal and aberrant biological pathways.

Anaesthetic impairment of immune function is mediated via GABA(A) receptors.

BACKGROUND: GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients. PRINCIPAL FINDINGS: We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin. SIGNIFICANCE: Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem.

Function Innovation in Combined Surface Technologies for Metals

表面技术能够显著提高材料功能而成为工程和产品设计的重要组成部分, 但前提是表面技术必须具有可设计性。为此, 需要开拓和发展表面组合加工技术, 进行创新。该技术的内涵体现了新材料与新技术、基础研究与产业化有机结合的特点, 具有重要的价值和广阔的前景。

Performance of low density parity check codes as a function of actual and assumed noise levels

We investigate how sensitive Gallager's codes are, when decoded by the sum-product algorithm, to the assumed noise level. We have found a remarkably simple function that fits the empirical results as a function of the actual noise level at both high and low noise levels. © 2004 Elsevier B.V.

Performance of low density parity check codes as a function of actual and assumed noise levels

We investigate how sensitive Gallager's codes are, when decoded by the sum-product algorithm, to the assumed noise level. We have found a remarkably simple function that fits the empirical results as a function of the actual noise level at both high and low noise levels. ©2003 Published by Elsevier Science B. V.

A Salmonella Typhimurium-Typhi genomic chimera: a model to study Vi polysaccharide capsule function in vivo.

The Vi capsular polysaccharide is a virulence-associated factor expressed by Salmonella enterica serotype Typhi but absent from virtually all other Salmonella serotypes. In order to study this determinant in vivo, we characterised a Vi-positive S. Typhimurium (C5.507 Vi(+)), harbouring the Salmonella pathogenicity island (SPI)-7, which encodes the Vi locus. S. Typhimurium C5.507 Vi(+) colonised and persisted in mice at similar levels compared to the parent strain, S. Typhimurium C5. However, the innate immune response to infection with C5.507 Vi(+) and SGB1, an isogenic derivative not expressing Vi, differed markedly. Infection with C5.507 Vi(+) resulted in a significant reduction in cellular trafficking of innate immune cells, including PMN and NK cells, compared to SGB1 Vi(-) infected animals. C5.507 Vi(+) infection stimulated reduced numbers of TNF-α, MIP-2 and perforin producing cells compared to SGB1 Vi(-). The modulating effect associated with Vi was not observed in MyD88(-/-) and was reduced in TLR4(-/-) mice. The presence of the Vi capsule also correlated with induction of the anti-inflammatory cytokine IL-10 in vivo, a factor that impacted on chemotaxis and the activation of immune cells in vitro.

Barium-Functionalized Multiwalled Carbon Nanotube Yarns As Low-Work-Function Thermionic Cathodes

Barium-functionalized multiwalled carbon nanotube yarns were fabricated by drawing and twisting multiwalled carbon nanotube forests through a solution containing barium nitrate. After heat activation under vacuum, the functionalized yarns were enriched in barium oxide due to the high surface-to-volume ratio of the nanotubes. The cathodes exhibited good thermionic properties, with a work function as low as 1.73-2.06 eV and thermionic current density that exceeded 185 mA/cm(2) in a field of 850 V/5 mm at 1317 K. The barium-functionalized yarns had high tensile strength of up to 420 MPa and retained strength of similar to 250 MPa after a 2 h activation process. (C) 2008 American Institute of Physics.

Semi-weight function method on computation of stress intensity factors in dissimilar materials

Semi-weight function method is developed to solve the plane problem of two bonded dissimilar materials containing a crack along the bond. From equilibrium equation, stress and strain relationship, conditions of continuity across interface and free crack surface, the stress and displacement fields were obtained. The eigenvalue of these fields is lambda. Semi-weight functions were obtained as virtual displacement and stress fields with eigenvalue-lambda. Integral expression of fracture parameters, K-I and K-II, were obtained from reciprocal work theorem with semi-weight functions and approximate displacement and stress values on any integral path around crack tip. The calculation results of applications show that the semi-weight function method is a simple, convenient and high precision calculation method.

Synchronization of modified Chua's circuit with x vertical bar x vertical bar function

This paper considers the chaos synchronization of the modified Chua's circuit with x vertical bar x vertical bar function. We firstly show that a couple of the modified Chua systems with different parameters and initial conditions can be synchronized using active control when the values of parameters both in drive system and response system are known aforehand. Furthermore, based on Lyapunov stability theory we propose an adaptive active control approach to make the states of two identical Chua systems with unknown constant parameters asymptotically synchronized. Moreover the designed controller is independent of those unknown parameters. Numerical simulations are given to validate the proposed synchronization approach.

Self-consistent kinetic modeling of electron distribution function in a low-pressure inductively coupled plasma

Based upon the spatially inhomogeneous Boltzmann equation in two-term approximation coupled with electromagnetic and fluid model analysis for the recently developed inductively coupled plasma sources, a self-consistent electron kinetic model is developed. The electron distribution function, spatial distributions of the electron density and ionization rate are calculated and discussed.