103 research outputs found

    Weak Localization Effect in Superconductors by Radiation Damage

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    Large reductions of the superconducting transition temperature TcT_{c} and the accompanying loss of the thermal electrical resistivity (electron-phonon interaction) due to radiation damage have been observed for several A15 compounds, Chevrel phase and Ternary superconductors, and NbSe2\rm{NbSe_{2}} in the high fluence regime. We examine these behaviors based on the recent theory of weak localization effect in superconductors. We find a good fitting to the experimental data. In particular, weak localization correction to the phonon-mediated interaction is derived from the density correlation function. It is shown that weak localization has a strong influence on both the phonon-mediated interaction and the electron-phonon interaction, which leads to the universal correlation of TcT_{c} and resistance ratio.Comment: 16 pages plus 3 figures, revtex, 76 references, For more information, Plesse see http://www.fen.bilkent.edu.tr/~yjki

    Antimycobacterial drug discovery using Mycobacteria-infected amoebae identifies anti-infectives and new molecular targets

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    Tuberculosis remains a serious threat to human health world-wide, and improved efficiency of medical treatment requires a better understanding of the pathogenesis and the discovery of new drugs. In the present study, we performed a whole-cell based screen in order to complete the characterization of 168 compounds from the GlaxoSmithKline TB-set. We have established and utilized novel previously unexplored host-model systems to characterize the GSK compounds, i.e. the amoeboid organisms D. discoideum and A. castellanii, as well as a microglial phagocytic cell line, BV2. We infected these host cells with Mycobacterium marinum to monitor and characterize the anti-infective activity of the compounds with quantitative fluorescence measurements and high-content microscopy. In summary, 88.1% of the compounds were confirmed as antibiotics against M. marinum, 11.3% and 4.8% displayed strong anti-infective activity in, respectively, the mammalian and protozoan infection models. Additionally, in the two systems, 13-14% of the compounds displayed pro-infective activity. Our studies underline the relevance of using evolutionarily distant pathogen and host models in order to reveal conserved mechanisms of virulence and defence, respectively, which are potential "universal" targets for intervention. Subsequent mechanism of action studies based on generation of over-expresser M. bovis BCG strains, generation of spontaneous resistant mutants and whole genome sequencing revealed four new molecular targets, including FbpA, MurC, MmpL3 and GlpK

    Arabidopsis R2R3-MYB transcription factor AtMYB60 functions as a transcriptional repressor of anthocyanin biosynthesis in lettuce (Lactuca sativa)

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    The MYB transcription factors play important roles in the regulation of many secondary metabolites at the transcriptional level. We evaluated the possible roles of the Arabidopsis R2R3-MYB transcription factors in flavonoid biosynthesis because they are induced by UV-B irradiation but their associated phenotypes are largely unexplored. We isolated their genes by RACE-PCR, and performed transgenic approach and metabolite analyses in lettuce (Lactuca sativa). We found that one member of this protein family, AtMYB60, inhibits anthocyanin biosynthesis in the lettuce plant. Wild-type lettuce normally accumulates anthocyanin, predominantly cyanidin and traces of delphinidin, and develops a red pigmentation. However, the production and accumulation of anthocyanin pigments in AtMYB60-overexpressing lettuce was inhibited. Using RT-PCR analysis, we also identified the complete absence or reduction of dihydroflavonol 4-reductase (DFR) transcripts in AtMYB60- overexpressing lettuce (AtMYB60-117 and AtMYB60-112 lines). The correlation between the overexpression of AtMYB60 and the inhibition of anthocyanin accumulation suggests that the transcription factorAtMYB60 controls anthocyanin biosynthesis in the lettuce leaf. Clarification of the roles of the AtMYB60 transcription factor will facilitate further studies and provide genetic tools to better understand the regulation in plants of the genes controlled by the MYB-type transcription factors. Furthermore, the characterization of AtMYB60 has implications for the development of new varieties of lettuce and other commercially important plants with metabolic engineering approaches

    Measuring local depletion of terrestrial game vertebrates by central-place hunters in rural Amazonia

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    The degree to which terrestrial vertebrate populations are depleted in tropical forests occupied by human communities has been the subject of an intense polarising debate that has important conservation implications. Conservation ecologists and practitioners are divided over the extent to which community-based subsistence offtake is compatible with ecologically functional populations of tropical forest game species. To quantify depletion envelopes of forest vertebrates around human communities, we deployed a total of 383 camera trap stations and 78 quantitative interviews to survey the peri-community areas controlled by 60 semi-subsistence communities over a combined area of over 3.2 million hectares in the Médio Juruá and Uatumã regions of Central-Western Brazilian Amazonia. Our results largely conform with prior evidence that hunting large-bodied vertebrates reduces wildlife populations near settlements, such that they are only found at a distance to settlements where they are hunted less frequently. Camera trap data suggest that a select few harvest-sensitive species, including lowland tapir, are either repelled or depleted by human communities. Nocturnal and cathemeral species were detected relatively more frequently in disturbed areas close to communities, but individual species did not necessarily shift their activity patterns. Group biomass of all species was depressed in the wider neighbourhood of urban areas rather than communities. Interview data suggest that species traits, especially group size and body mass, mediate these relationships. Large-bodied, large-group-living species are detected farther from communities as reported by experienced informants. Long-established communities in our study regions have not “emptied” the surrounding forest. Low human population density and low hunting offtake due to abundant sources of alternative aquatic protein, suggest that these communities represent a best-case scenario for sustainable hunting of wildlife for food, thereby providing a conservative assessment of game depletion. Given this ‘best-case’ camera trap and interview-based evidence for hunting depletion, regions with higher human population densities, external trade in wildlife and limited access to alternative protein will likely exhibit more severe depletion

    Combined linkage and linkage disequilibrium analysis of a motor speech phenotype within families ascertained for autism risk loci

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    Using behavioral and genetic information from the Autism Genetics Resource Exchange (AGRE) data set we developed phenotypes and investigated linkage and association for individuals with and without Autism Spectrum Disorders (ASD) who exhibit expressive language behaviors consistent with a motor speech disorder. Speech and language variables from Autism Diagnostic Interview-Revised (ADI-R) were used to develop a motor speech phenotype associated with non-verbal or unintelligible verbal behaviors (NVMSD:ALL) and a related phenotype restricted to individuals without significant comprehension difficulties (NVMSD:C). Using Affymetrix 5.0 data, the PPL framework was employed to assess the strength of evidence for or against trait-marker linkage and linkage disequilibrium (LD) across the genome. Ingenuity Pathway Analysis (IPA) was then utilized to identify potential genes for further investigation. We identified several linkage peaks based on two related language-speech phenotypes consistent with a potential motor speech disorder: chromosomes 1q24.2, 3q25.31, 4q22.3, 5p12, 5q33.1, 17p12, 17q11.2, and 17q22 for NVMSD:ALL and 4p15.2 and 21q22.2 for NVMSD:C. While no compelling evidence of association was obtained under those peaks, we identified several potential genes of interest using IPA. Conclusion: Several linkage peaks were identified based on two motor speech phenotypes. In the absence of evidence of association under these peaks, we suggest genes for further investigation based on their biological functions. Given that autism spectrum disorders are complex with a wide range of behaviors and a large number of underlying genes, these speech phenotypes may belong to a group of several that should be considered when developing narrow, well-defined, phenotypes in the attempt to reduce genetic heterogeneity

    Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

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    New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide1, 2. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis3, 4, 5, several of which are currently in clinical trials6, 7, 8. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis

    Superconducting spintronics

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    The interaction between superconducting and spin-polarized orders has recently emerged as a major research field following a series of fundamental breakthroughs in charge transport in superconductor-ferromagnet heterodevices which promise new device functionality. Traditional studies which combine spintronics and superconductivity have mainly focused on the injection of spin-polarized quasiparticles into superconducting materials. However, a complete synergy between superconducting and magnetic orders turns out to be possible through the creation of spin-triplet Cooper pairs which are generated at carefully engineered superconductor interfaces with ferromagnetic materials. Currently, there is intense activity focused on identifying materials combinations which merge superconductivity and spintronics in order to enhance device functionality and performance. The results look promising: it has been shown, for example, that superconducting order can greatly enhance central effects in spintronics such as spin injection and magnetoresistance. Here, we review the experimental and theoretical advances in this field and provide an outlook for upcoming challenges related to the new concept of superconducting spintronics.J.L. was supported by the Research Council of Norway, Grants No. 205591 and 216700. J.W.A.R. was supported by the UK Royal Society and the Leverhulme Trust through an International Network Grant (IN-2013-033).This is the accepted manuscript. The final version is available at http://www.nature.com/nphys/journal/v11/n4/full/nphys3242.html

    CXCL10 and ILâ 6: Markers of two different forms of intraâ amniotic inflammation in preterm labor

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137580/1/aji12685_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137580/2/aji12685.pd

    Asymmetric perturbations of signalling oligomers

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    Exploring new physics frontiers through numerical relativity

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    The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology
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