33 research outputs found

    Uniaxial versus biaxial character of nematic equilibria in three dimensions

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    We study global minimizers of the Landau–de Gennes (LdG) energy functional for nematic liquid crystals, on arbitrary three-dimensional simply connected geometries with topologically non-trivial and physically relevant Dirichlet boundary conditions. Our results are specific to an asymptotic limit coined in terms of a dimensionless temperature and material-dependent parameter, t and some constraints on the material parameters, and we work in the t→∞ limit that captures features of the widely used Lyuksyutov constraint (Kralj and Virga in J Phys A 34:829–838, 2001). We prove (i) that (re-scaled) global LdG minimizers converge uniformly to a (minimizing) limiting harmonic map, away from the singular set of the limiting map; (ii) we have points of maximal biaxiality and uniaxiality near each singular point of the limiting map; (iii) estimates for the size of “strongly biaxial” regions in terms of the parameter t. We further show that global LdG minimizers in the restricted class of uniaxial Q-tensors cannot be stable critical points of the LdG energy in this limit

    Analysis of eight genes modulating interferon gamma and human genetic susceptibility to tuberculosis: a case-control association study

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    <p>Abstract</p> <p>Background</p> <p>Interferon gamma is a major macrophage-activating cytokine during infection with <it>Mycobacterium tuberculosis</it>, the causative pathogen of tuberculosis, and its role has been well established in animal models and in humans. This cytokine is produced by activated T helper 1 cells, which can best deal with intracellular pathogens such as <it>M. tuberculosis</it>. Based on the hypothesis that genes which regulate interferon gamma may influence tuberculosis susceptibility, we investigated polymorphisms in eight candidate genes.</p> <p>Methods</p> <p>Fifty-four polymorphisms in eight candidate genes were genotyped in over 800 tuberculosis cases and healthy controls in a population-based case-control association study in a South African population. Genotyping methods used included the SNPlex Genotyping System™, capillary electrophoresis of fluorescently labelled PCR products, TaqMan<sup>® </sup>SNP genotyping assays or the amplification mutation refraction system. Single polymorphisms as well as haplotypes of the variants were tested for association with TB using statistical analyses.</p> <p>Results</p> <p>A haplotype in interleukin 12B was nominally associated with tuberculosis (p = 0.02), but after permutation testing, done to assess the significance for the entire analysis, this was not globally significant. In addition a novel allele was found for the interleukin 12B D5S2941 microsatellite.</p> <p>Conclusions</p> <p>This study highlights the importance of using larger sample sizes when attempting validation of previously reported genetic associations. Initial studies may be false positives or may propose a stronger genetic effect than subsequently found to be the case.</p

    In Vitro and In Vivo Efficacy of Ether Lipid Edelfosine against Leishmania spp. and SbV-Resistant Parasites

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    Leishmaniasis represents a major international health problem, has a high morbidity and mortality rate, and is classified as an emerging and uncontrolled disease by the World Health Organization. The migration of population from endemic to nonendemic areas, and tourist activities in endemic regions are spreading the disease to new areas. Unfortunately, treatment of leishmaniasis is far from satisfactory, with only a few drugs available that show significant side-effects. Here, we show in vitro and in vivo evidence for the antileishmanial activity of the ether phospholipid edelfosine, being effective against a wide number of Leishmania spp. causing cutaneous, mucocutaneous and visceral leishmaniasis. Our experimental mouse and hamster models demonstrated not only a significant antileishmanial activity of edelfosine oral administration against different wild-type Leishmania spp., but also against parasites resistant to pentavalent antimonials, which constitute the first line of treatment worldwide. In addition, edelfosine exerted a higher antileishmanial activity and a lower proneness to generate drug resistance than miltefosine, the first drug against leishmaniasis that can be administered orally. These data, together with our previous findings, showing an anti-inflammatory action and a very low toxicity profile, suggest that edelfosine is a promising orally administered drug for leishmaniasis, thus warranting clinical evaluation
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