Search

Human lung mast cells (HLMCs) express the high-affinity receptor FcεRI for IgE and are involved in chronic pulmonary diseases occurring at high frequency among HIV-infected individuals. Immunoglobulin superantigens bind to the variable regions of either the heavy or light chain of immunoglobulins (Igs). Glycoprotein 120 (gp120) of HIV-1 is a typical immunoglobulin superantigen interacting with the heavy chain, variable 3 (VH3) region of human Igs. The present study investigated whether immunoglobulin superantigen gp120 caused the release of different classes of proinflammatory and immunoregulatory mediators from HLMCs. The results show that gp120 from different clades induced the rapid (30 min) release of preformed mediators (histamine and tryptase) from HLMCs. gp120 also caused the de novo synthesis of cysteinyl leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) from HLMCs. Incubation (6 h) of HLMC with gp120 induced the release of angiogenic (VEGF-A) and lymphangiogenic (VEGF-C) factors from HLMCs. The activating property of gp120 was mediated through the interaction with IgE VH3+ bound to FcεRI. Our data indicate that HIV gp120 is a viral superantigen, which induces the release of different proinflammatory, angiogenic, and lymphangiogenic factors from HLMCs. These observations could contribute to understanding, at least in part, the pathophysiology of chronic pulmonary diseases in HIV-infected individuals.

The current experimental work focusses on the parallel channel instability and possible premature critical heat flux in a short, narrow multi-microchannel heat sink with and without individual channel inlet restrictions. The application was cooling of power electronics and the target footprint area was (10 x 10) mm2. The heat sink was fabricated in copper by micro-milling and had 25 rectangular channels (198 μm wide, 1167 μm high). The heat sink featured customized exchangeable PEEK inserts, which constituted the inlet and outlet plenums as well as featuring the individual channel inlet restrictions, which had a 40 % area contraction compared with the channel area. Refrigerant R134a was adopted as the working fluid and the critical heat flux was measured at several different mass fluxes and different inlet subcooling at around 31 °C saturation temperature with and without inlet restriction. High-speed visualization was used to study the flow patterns and two-phase instability. The visualizations showed that the inlet restrictions stabilized the flow with respect to the parallel channel instability that was otherwise present at lower mass fluxes, thus avoiding vapour backflow into the inlet plenum. At higher mass fluxes, the visualizations did not indicate significant vapour backflow with or without individual channel inlet restrictions. Fourier analysis was used to study the instability atthe lowest mass flux (339 kg/m2s) at a subcooling of 5.2 K without inlet restriction. Here the main frequency of the twophase oscillations was very fast (14􀀚􀀑􀀘 Hz) and systematic. The absolute pressure sensors captured twice this frequency: This is in good agreement since these sensors captured the vapour backflow from both ends of the channel row. The current high frequency two-phase oscillations led to a marginally lower critical heat flux (2-9 %) without use of the individual channel inlet restrictions.

Anti-viral activities of long-chain inorganic polyphosphates (PolyPs) against severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection were investigated. In molecular docking analyses, PolyPs interacted with several conserved angiotensin-converting enzyme (ACE)2 and RNA-dependent RNA polymerase (RdRp) amino acids. We thus tested PolyPs for functional interactionsin vitroin SARS-CoV-2–infected Vero E6, Caco2 and human primary nasal epithelial cells. Immunofluorescence, qPCR, direct RNA sequencing, FISH and Immunoblotting were used to determine virus loads and transcription levels of genomic(g)RNAs and sub-genomic(sg)RNAs. We show that PolyP120 binds to ACE2 and enhances its proteasomal degradation. PolyP120 shows steric hindrance of the genomic Sars-CoV-2-RNA/RdRP complex, to impair synthesis of positive-sense gRNAs, viral subgenomic transcripts and structural proteins needed for viral replication. Thus, PolyP120 impairs infection and replication of Korean and European (containing non-synonymous variants) SARS-CoV-2 strains. As PolyPs have no toxic activities, we envision their use as a nebulised formula for oropharyngeal delivery to prevent infections of SARS-CoV-2 and during early phases of antiviral therapy.

HYPOTHESIS: We have proposed that VEG/PF acts by transforming the cytoskeletal architecture of microvascular endothelial cells. BACKGROUND: Evidence supporting a pivotal role for vascular endothelial growth/permeability factor (VEG/PF) in tumor angiogenesis and edemagenesis is compelling. VEG/PF exhibits specific endothelial cell mitogenicity and is expressed by brain tumors exhibiting increased vascularity and microvascular extravasation. The mechanistic cascade that follows VEG/PF-tyrosine kinase receptor binding remains uncertain, however. Actin is a cytoskeletal protein that regulates cellular motility, shape and vesicular transport. Regulation of actin stress fibers, cell-surface focal adhesions and plasmalemmal "ruffles" is mediated by tyrosine kinase activation of GTP-binding proteins that are in turn linked to intracellular calcium flux. As VEG/PF is known to induce cytosolic calcium ion transients in endothelial cells, actin microfilaments would appear to be logical candidates for study of a cytocontractile response mediated by calcium signal transduction. METHODS: VEG/PF-induced endothelial actin cytoskeletal changes were studied using rhodamine phalloidin staining and fluorescence photomicrography. RESULTS: When exposed to VEG/PF, cultured endothelial cells from human umbilical veins and rat brain microvessels exhibited a reversible, dose-related reorganization of actin stress fibers, cell contraction and rounding, and widening of the intercellular spaces. VEG/PF perturbation also induced plasmalemmal "ruffling". All VEG/PF-induced cytoskeletal changes were inhibited by preincubating endothelial cells with dexamethasone or anti-VEG/PF IgG antibody. CONCLUSION: The findings support a role for VEG/PF-induced cytoskeletal alterations in the pathophysiology of brain tumor angiogenesis and edemagenesis. These observations are likely to be directly linked to VEG/PF-induced endothelial cytosolic calcium flux. Insight into the mechanism of dexamethasone's clinical efficacy is also provided. Images Figure 1A Figure 1B Figure 1C Figure 2 Figure 3A Figure 3B Figure 3C Figure 3D Figure 4A Figure 4B Figure 4C Figure 5 Figures 6A Figures 6B Figures 6C

Nitrate is an essential element for plant growth, both as a primary nutrient in the nitrogen assimilation pathway and as an important signal for plant development. Low- and high-affinity transport systems are involved in the nitrate uptake from the soil and its distribution between different plant tissues. By an in silico search, we identified putative members of both systems in the model legume Lotus japonicus. We investigated, by a time course analysis, the transcripts abundance in root tissues of nine and four genes encoding putative low-affinity (NRT1) and high-affinity (NRT2) nitrate transporters, respectively. The genes were sub-classified as inducible, repressible and constitutive on the basis of their responses to provision of nitrate, auxin or cytokinin. Furthermore, the analysis of the pattern of expression in root and nodule tissues after Mesorhizobium loti inoculation permitted the identification of sequences significantly regulated during the symbiotic interaction. The interpretation of the global regulative networks obtained allowed to postulate roles for nitrate transporters as possible actors in the cross-talks between different signalling pathways triggered by biotic and abiotic factors.

This paper describes a collocation method for solving numerically a singular integral equation with Cauchy and Volterra operators, associated with a proper constraint condition. The numerical method is based on the transformation of the given integral problem into a hypersingular integral equation and then applying a collocation method to solve the latter equation. Convergence of the resulting method is then discussed, and optimal convergence rates for the collocation and discrete collocation methods are given in suitable weighted Sobolev spaces. Numerical examples are solved using the proposed numerical technique.

Capobianco, Criscuolo and Junghanns [2] have studied an integro differential equation of Prandtl type and a collocation method as well as a quadrature method for its approximate solution in weighted Sobolev spaces. Furthermore, collocation and collocation quadrature methods for the same integral equation have been studied in weighted spaces of continuous functions [3]. The aim of the present paper is to present an algorithm related to a numerical model for a hypersingular Integral equation arising in a solid circular plate problem, based on the collocation methods with quadrature methods on orthogonal polynomials as in [2, 3]. The optimal convergence rates is proved.

The analysis of the convergence and stability theory is carried out for a class of integrals accessible to Gauss quadrature as singular principal value integrals. Numerical examples confirming the theoretical results are also given.

In this paper the authors give a different and more precise analysis of the stability of the classical Gauss-Laguerre quadrature rule for the Cauchy P.V. integrals on the half line. Moreover, in order to obtain this result they give some new estimates for the distance of the zeros of the Laguerre polynomials that can be useful also in other contests.

In this paper we apply Newton's method and its modified version to discrete equations obtained by applying a collocation method to a class of nonlinear integro-differential equations. We prove the convergence of these methods in some Sobolev type spaces.

For the numerical solution of the hypersingular integral equation of a notched half plane problem we propose collocation methods which look for an approximation of the derivative of the solution of the original equation. This derivative is the solution of a Cauchy singular integral equation with additional fixed singularities. We also give a solvability analysis of the original equation which motivates the suggested numerical methods.

An account of the error and of the convergence theory is given for Gauss-Laguerre quadrature formulae. We develop also truncated models of the original Gauss rules to compute integrals extended over the positive real axis.

In this paper we analyze the numerical solution by a collocation method of a hypersingular integral equation resulting from the boundary value problem related to an infinite strip containing an edge crack perpendicular to its boundaries. Moreover, we show convergence results as well as numerical tests in a case of interest in fracture mechanics

In this paper we consider a collocation and a discrete collocation method for a Volterra integral equation with logarithmic perturbation kernel. We prove convergence and stability of these methods in a pair of Sobolev type spaces.

In this paper we consider a class of strongly singular, nonlinear integral equations. A numerical method is proposed and its convergence is proved in weighted Sobolev spaces.

Collocation and quadrature methods for singular integro-differential equations of Prandtl's type are studied in weighted Sobolev spaces as well as in weighted spaces of continuous functions. A fast algorithm based on the quadrature method is proposed. Convergence results and error estimates are given.

We deal with the numerical evaluation of integrals of functions with strong singularities often used in applications. The convergence and the stability of the methods for the numerical computation of such integrals is investigated. The goodness of the numerical results for pratical applications are examined.

We deal with the numerical evaluation of the Hilbert transform on the real line by a Gauss type quadrature rule. The convergence and the stability of the method are investigated.