Direct correlation functions of the Widom-Rowlinson model

We calculate, through Monte Carlo numerical simulations, the partial total and direct correlation functions of the three dimensional symmetric Widom-Rowlinson mixture. We find that the differences between the partial direct correlation functions from simulation and from the Percus-Yevick approximation (calculated analytically by Ahn and Lebowitz) are well fitted by Gaussians. We provide an analytical expression for the fit parameters as function of the density. We also present Monte Carlo simulation data for the direct correlation functions of a couple of non additive hard sphere systems to discuss the modification induced by finite like diameters.Comment: 16 pages, 7 figure

Advances for the topographic characterisation of SMC materials

For a comprehensive study of Sheet Moulding Compound (SMC) surfaces, topographical data obtained by a contact-free optical method (chromatic aberration confocal imaging) were systematically acquired to characterise these surfaces with regard to their statistical, functional and volumetrical properties. Optimal sampling conditions (cut-off length and resolution) were obtained by a topographical-statistical procedure proposed in the present work. By using different length scales specific morphologies due to the influence of moulding conditions, metallic mould topography, glass fibre content and glass fibre orientation can be characterized. The aim of this study is to suggest a systematic topographical characterization procedure for composite materials in order to study and recognize the influence of production conditions on their surface quality. © 2009 by the authors

Importance sampling for integrated market and credit portfolio models

Abstract: Standard credit portfolio models do not model market risk factors, such as risk-free interest rates or credit spreads, as stochastic variables. Various studies have documented that a severe underestimation of economic capital can be the consequence. However, integrating market risk factors into credit portfolio models increases the computational burden of computing credit portfolio risk measures. In this paper, the application of various importance sampling techniques to an integrated market and credit portfolio model are presented and the effectiveness of these approaches is tested by numerical experiments. The main result is that importance sampling can reduce the standard error of the percentile estimators, but it is rather difficult to make statements about when the IS approach is especially effective. Besides, the combination of importance sampling techniques originally developed for pure market risk portfolio models with techniques originally developed for pure default mode credit risk portfolio models is less effective than simpler two step-IS approaches

Modulation of GSK-3-catalyzed phosphorylation of microtubule-associated protein tau by non-proline-dependent protein kinases

AbstractThe phosphorylation of bovine tau, either by GSK-3 alone or by a combination of GSK-3 and several non-proline-dependent protein kinases (non-PDPKs), was studied. GSK-3 alone catalyzed the incorporation of ∼ 3 mol 32P/mot tau at a relatively slow rate. Prephosphorylation of tau by A-kinase, C-kinase, or CK-2 (but not by CK-1, CaM kinase II or Gr kinase) increased both the rate and extent of a subsequent phosphorylation catalyzed by GSK-3 by several-fold. These results suggest that the phosphorylation of tau by PDPKs such as GSK-3 (and possibly MAP kinase, cdk5) may be positively modulated at the substrate level by non-PDPK-catalyzed phosphorylations

Role of protein phosphatase-2A and -1 in the regulation of GSK-3, cdk5 and cdc2 and the phosphorylation of tau in rat forebrain

AbstractIn Alzheimer disease brain the activities of protein phosphatase (PP)-2A and PP-1 are decreased and the microtubule-associated protein tau is abnormally hyperphosphorylated at several sites at serine/threonine. Employing rat forebrain slices kept metabolically active in oxygenated artificial CSF as a model system, we investigated the role of PP-2A/PP-1 in the regulation of some of the major abnormally hyperphosphorylated sites of tau and the protein kinases involved. Treatment of the brain slices with 1.0 μM okadaic acid inhibited ∼65% of PP-2A and produced hyperphosphorylation of tau at Ser 198/199/202, Ser 396/404 and Ser 422. No significant changes in the activities of glycogen synthase kinase-3 (GSK-3) and cyclin dependent protein kinases cdk5 and cdc2 were observed. Calyculin A (0.1 μM) inhibited ∼50% PP-1, ∼20% PP-2A, 50% GSK-3 and ∼30% cdk5 but neither inhibited the activity of cyclin AMP dependent protein kinase A (PKA) nor resulted in the hyperphosphorylation of tau at any of the above sites. Treatment of brain slices with 1 μM okadaic acid plus 0.1 μM calyculin A inhibited ∼100% of both PP-2A and PP-1, ∼80% of GSK-3, ∼50% of cdk5 and ∼30% of cdc2 but neither inhibited PKA nor resulted in the hyperphosphorylation of tau at any of the above sites. These studies suggest (i) that PP-1 upregulates the phosphorylation of tau at Ser 198/199/202 and Ser 396/404 indirectly by regulating the activities of GSK-3, cdk5 and cdc2 whereas PP-2A regulates the phosphorylation of tau directly by dephosphorylation at the above sites, and (ii) that a decrease in the PP-2A activity leads to abnormal hyperphosphorylation of tau at Ser 198/199/202, Ser 396/404 and Ser 422

Dysregulation of Protein Phosphorylation/Dephosphorylation in Alzheimer's Disease: A Therapeutic Target

Studies during the last two decades have provided new insights into the molecular mechanism of Alzheimer's disease (AD). One of the milestone findings in AD research was the demonstration that neurofibrillary degeneration characterized by tau pathology is central to the pathogenesis of AD and other tauopathies and that abnormal hyperphosphorylation of tau is pivotal to neurofibrillary degeneration. This article reviews the recent research advances in tau pathology and the underlying dysregulation of the protein phosphorylation/dephosphorylation system. An updated model of the mechanism of neurofibrillary degeneration is also presented, and a promising therapeutic target to treat AD by correcting dysregulation of protein phosphorylation/dephosphorylation is discussed