36 research outputs found

    Spin-transfer in an open ferromagnetic layer: from negative damping to effective temperature

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    Spin-transfer is a typical spintronics effect that allows a ferromagnetic layer to be switched by spin-injection. Most of the experimental results about spin transfer are described on the basis of the Landau-Lifshitz-Gilbert equation of the magnetization, in which additional current-dependent damping factors are added, and can be positive or negative. The origin of the damping can be investigated further by performing stochastic experiments, like one shot relaxation experiments under spin-injection in the activation regime of the magnetization. In this regime, the N\'eel-Brown activation law is observed which leads to the introduction of a current-dependent effective temperature. In order to justify the introduction of these counterintuitive parameters (effective temperature and negative damping), a detailed thermokinetic analysis of the different sub-systems involved is performed. We propose a thermokinetic description of the different forms of energy exchanged between the electric and the ferromagnetic sub-systems at a Normal/Ferromagnetic junction. The corresponding Fokker Planck equations, including relaxations, are derived. The damping coefficients are studied in terms of Onsager-Casimir transport coefficients, with the help of the reciprocity relations. The effective temperature is deduced in the activation regime.Comment: 65 pages, 10 figure

    Antimicrobial Peptides and Skin: A Paradigm of Translational Medicine

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    Antimicrobial peptides (AMPs) are small, cationic, amphiphilic peptides with broad-spectrum microbicidal activity against both bacteria and fungi. In mammals, AMPs form the first line of host defense against infections and generally play an important role as effector agents of the innate immune system. The AMP era was born more than 6 decades ago when the first cationic cyclic peptide antibiotics, namely polymyxins and tyrothricin, found their way into clinical use. Due to the good clinical experience in the treatment of, for example, infections of mucus membranes as well as the subsequent understanding of mode of action, AMPs are now considered for treatment of inflammatory skin diseases and for improving healing of infected wounds. Based on the preclinical findings, including pathobiochemistry and molecular medicine, targeted therapy strategies are developed and first results indicate that AMPs influence processes of diseased skin. Importantly, in contrast to other antibiotics, AMPs do not seem to propagate the development of antibiotic-resistant micro-organisms. Therefore, AMPs should be tested in clinical trials for their efficacy and tolerability in inflammatory skin diseases and chronic wounds. Apart from possible fields of application, these peptides appear suited as an example of the paradigm of translational medicine for skin diseases which is today seen as a `two-way road' - from bench to bedside and backwards from bedside to bench. Copyright (c) 2012 S. Karger AG, Base

    Antimicrobial and Efflux Pump Inhibitory Activity of Caffeoylquinic Acids from Artemisia absinthium against Gram-Positive Pathogenic Bacteria

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    Background: Traditional antibiotics are increasingly suffering from the emergence of multidrug resistance amongst pathogenic bacteria leading to a range of novel approaches to control microbial infections being investigated as potential alternative treatments. One plausible antimicrobial alternative could be the combination of conventional antimicrobial agents/antibiotics with small molecules which block multidrug efflux systems known as efflux pump inhibitors. Bioassay-driven purification and structural determination of compounds from plant sources have yielded a number of pump inhibitors which acted against gram positive bacteria. Methodology/Principal Findings: In this study we report the identification and characterization of 4′,5′-O-dicaffeoylquinic acid (4′,5′-ODCQA) from Artemisia absinthium as a pump inhibitor with a potential of targeting efflux systems in a wide panel of Gram-positive human pathogenic bacteria. Separation and identification of phenolic compounds (chlorogenic acid, 3′,5′-ODCQA, 4′,5′-ODCQA) was based on hyphenated chromatographic techniques such as liquid chromatography with post column solid-phase extraction coupled with nuclear magnetic resonance spectroscopy and mass spectroscopy. Microbial susceptibility testing and potentiation of well know pump substrates revealed at least two active compounds; chlorogenic acid with weak antimicrobial activity and 4′,5′-ODCQA with pump inhibitory activity whereas 3′,5′-ODCQA was ineffective. These intitial findings were further validated with checkerboard, berberine accumulation efflux assays using efflux-related phenotypes and clinical isolates as well as molecular modeling methodology. Conclusions/Significance: These techniques facilitated the direct analysis of the active components from plant extracts, as well as dramatically reduced the time needed to analyze the compounds, without the need for prior isolation. The calculated energetics of the docking poses supported the biological information for the inhibitory capabilities of 4′,5′-ODCQA and furthermore contributed evidence that CQAs show a preferential binding to Major Facilitator Super family efflux systems, a key multidrug resistance determinant in gram-positive bacteria.National Institutes of Health (U.S.) (grant R01GM59903)National Institutes of Health (U.S.) (grant R01AI050875)Netherlands Organization for Scientific Research (VICI grant 700.56.442)Massachusetts Technology Transfer Center (MTTC)National Institutes of Health (U.S.) (grant 5U54MH084690-02

    Cathelicidin-like Helminth Defence Molecules (HDMs) Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation

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    Host defence peptides (HDPs) are expressed throughout the animal and plant kingdoms. They have multifunctional roles in the defence against infectious agents of mammals, possessing both bactericidal and immune-modulatory activities. We have identified a novel family of molecules secreted by helminth parasites (helminth defence molecules; HDMs) that exhibit similar structural and biochemical characteristics to the HDPs. Here, we have analyzed the functional activities of four HDMs derived from Schistosoma mansoni and Fasciola hepatica and compared them to human, mouse, bovine and sheep HDPs. Unlike the mammalian HDPs the helminth-derived HDMs show no antimicrobial activity and are non-cytotoxic to mammalian cells (macrophages and red blood cells). However, both the mammalian- and helminth-derived peptides suppress the activation of macrophages by microbial stimuli and alter the response of B cells to cytokine stimulation. Therefore, we hypothesise that HDMs represent a novel family of HDPs that evolved to regulate the immune responses of their mammalian hosts by retaining potent immune modulatory properties without causing deleterious cytotoxic effects. © 2013 Thivierge et al

    Human Antimicrobial Peptide LL-37 Inhibits Adhesion of Candida albicans by Interacting with Yeast Cell-Wall Carbohydrates

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    Candida albicans is the major fungal pathogen of humans. Fungal adhesion to host cells is the first step of mucosal infiltration. Antimicrobial peptides play important roles in the initial mucosal defense against C. albicans infection. LL-37 is the only member of the human cathelicidin family of antimicrobial peptides and is commonly expressed in various tissues and cells, including epithelial cells of both the oral cavity and urogenital tract. We found that, at sufficiently low concentrations that do not kill the fungus, LL-37 was still able to reduce C. albicans infectivity by inhibiting C. albicans adhesion to plastic surfaces, oral epidermoid OECM-1 cells, and urinary bladders of female BALB/c mice. Moreover, LL-37-treated C. albicans floating cells that did not adhere to the underlying substratum aggregated as a consequence of LL-37 bound to the cell surfaces. According to the results of a competition assay, the inhibitory effects of LL-37 on cell adhesion and aggregation were mediated by its preferential binding to mannan, the main component of the C. albicans cell wall, and partially by its ability to bind chitin or glucan, which underlie the mannan layer. Therefore, targeting of cell-wall carbohydrates by LL-37 provides a new strategy to prevent C. albicans infection, and LL-37 is a useful, new tool to screen for other C. albicans components involved in adhesion

    A CONSEQUENCE OF POST-IMPACT RADIAL PROFILE SHAPE OF INDENTATION. PART II- A POSSIBLE EXPLANATION

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    A CONSEQUENCE OF POST-IMPACT RADIAL PROFILE SHAPE OF INDENTATION. PART II- A POSSIBLE EXPLANATION

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    The shape of the radial profile of a rotating disc, is different in the case when a free falling ball collides the disc, presents in the region between the imprint and the periphery of the disc a different shape from the one it has in the absence of contact. Accepting, in accordance with Saint-Venant’s principle that at distances far enough from the region the load is applied, it doesn’t matter the manner of applying the load, under the hypothesis of the linear elastic behaviour of material and using a FEA software, the phenomenon is modelled. There were considered the cases of the rotating disc without impact, the impact of free falling ball with the resting disc and the impact with the rotating disc and for neither one of the situations the material in the vicinity of the disc periphery reaches the plastic deformation domain

    Public support for European solidarity: Between Euroscepticism and EU agenda preferences?

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    This article investigates public support for two types of EU‐wide solidarity that currently exist, namely member state solidarity (such as transfers to less developed and crisis‐hit countries) and transnational solidarity (such as granting cross‐border social rights to EU citizens). Drawing on data from the 2014 Belgian National Election Study, we find that opposition towards European integration – in particular regarding EU enlargement – reduces citizens' willingness to support European solidarity to a large extent. However, this article reveals that public support for European solidarity cannot simply be reduced to a pro‐versus anti‐integration, nor to a domestic left–right conflict. Citizens' substantive positions towards the EU's social and economic agenda are a crucial element in understanding contestation over European integration issues
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