393 research outputs found

    Textures and Semi-Local Strings in SUSY Hybrid Inflation

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    Global topological defects may account for the large cold spot observed in the Cosmic Microwave Background. We explore possibilities of constructing models of supersymmetric F-term hybrid inflation, where the waterfall fields are globally SU(2)-symmetric. In contrast to the case where SU(2) is gauged, there arise Goldstone bosons and additional moduli, which are lifted only by masses of soft-supersymmetry breaking scale. The model predicts the existence of global textures, which can become semi-local strings if the waterfall fields are gauged under U(1)_X. Gravitino overproduction can be avoided if reheating proceeds via the light SU(2)-modes or right-handed sneutrinos. For values of the inflaton- waterfall coupling >=10^-4, the symmetry breaking scale imposed by normalisation of the power spectrum generated from inflation coincides with the energy scale required to explain the most prominent of the cold spots. In this case, the spectrum of density fluctuations is close to scale-invariant which can be reconciled with measurements of the power spectrum by the inclusion of the sub-dominant component due to the topological defects.Comment: 29 page

    Role of Common Genetic Variants for Drug-Resistance to Specific Anti-Seizure Medications

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    OBJECTIVE: Resistance to anti-seizure medications (ASMs) presents a significant hurdle in the treatment of people with epilepsy. Genetic markers for resistance to individual ASMs could support clinicians to make better-informed choices for their patients. In this study, we aimed to elucidate whether the response to individual ASMs was associated with common genetic variation. METHODS: A cohort of 3,649 individuals of European descent with epilepsy was deeply phenotyped and underwent single nucleotide polymorphism (SNP)-genotyping. We conducted genome-wide association analyses (GWASs) on responders to specific ASMs or groups of functionally related ASMs, using non-responders as controls. We performed a polygenic risk score (PRS) analyses based on risk variants for epilepsy and neuropsychiatric disorders and ASM resistance itself to delineate the polygenic burden of ASM-specific drug resistance. RESULTS: We identified several potential regions of interest but did not detect genome-wide significant loci for ASM-specific response. We did not find polygenic risk for epilepsy, neuropsychiatric disorders, and drug-resistance associated with drug response to specific ASMs or mechanistically related groups of ASMs. SIGNIFICANCE: This study could not ascertain the predictive value of common genetic variants for ASM responder status. The identified suggestive loci will need replication in future studies of a larger scal

    Pathway to the Square Kilometre Array - The German White Paper -

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    The Square Kilometre Array (SKA) is the most ambitious radio telescope ever planned. With a collecting area of about a square kilometre, the SKA will be far superior in sensitivity and observing speed to all current radio facilities. The scientific capability promised by the SKA and its technological challenges provide an ideal base for interdisciplinary research, technology transfer, and collaboration between universities, research centres and industry. The SKA in the radio regime and the European Extreme Large Telescope (E-ELT) in the optical band are on the roadmap of the European Strategy Forum for Research Infrastructures (ESFRI) and have been recognised as the essential facilities for European research in astronomy. This "White Paper" outlines the German science and R&D interests in the SKA project and will provide the basis for future funding applications to secure German involvement in the Square Kilometre Array.Comment: Editors: H. R. Kl\"ockner, M. Kramer, H. Falcke, D.J. Schwarz, A. Eckart, G. Kauffmann, A. Zensus; 150 pages (low resolution- and colour-scale images), published in July 2012, language English (including a foreword and an executive summary in German), the original file is available via the MPIfR homepag

    Simultaneous Quantification and Visualization of Titanium Dioxide Nanomaterial Uptake at the Single Cell Level in an In Vitro Model of the Human Small Intestine

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    International audienceUseful properties render titanium dioxide nanomaterials (NMs) to be one of the most commonly used NMs worldwide. TiO2 powder is used as food additives (E171), which may contain up to 36% nanoparticles. Consequently, humans could be exposed to comparatively high amounts of NMs that may induce adverse effects of chronic exposure conditions. Visualization and quantification of cellular NM uptake as well as their interactions with biomolecules within cells are key issues regarding risk assessment. Advanced quantitative imaging tools for NM detection within biological environments are therefore required. A combination of the label-free spatially resolved dosimetric tools, microresolved particle induced X-ray emission and Rutherford backscattering, together with high resolution imaging techniques, such as time-of-flight secondary ion mass spectrometry and transmission electron microscopy, are applied to visualize the cellular translocation pattern of TiO2 NMs and to quantify the NM-load, cellular major, and trace elements in differentiated Caco-2 cells as a function of their surface properties at the single cell level. Internalized NMs are not only able to impair the cellular homeostasis by themselves, but also to induce an intracellular redistribution of metabolically relevant elements such as phosphorus, sulfur, iron, and copper

    Assessing the role of rare genetic variants in drug-resistant, non-lesional focal epilepsy.

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    OBJECTIVE: Resistance to antiseizure medications (ASMs) is one of the major concerns in the treatment of epilepsy. Despite the increasing number of ASMs available, the proportion of individuals with drug-resistant epilepsy remains unchanged. In this study, we aimed to investigate the role of rare genetic variants in ASM resistance. METHODS: We performed exome sequencing of 1,128 individuals with non-familial non-acquired focal epilepsy (NAFE) (762 non-responders, 366 responders) and were provided with 1,734 healthy controls. We undertook replication in a cohort of 350 individuals with NAFE (165 non-responders, 185 responders). We performed gene-based and gene-set-based kernel association tests to investigate potential enrichment of rare variants in relation to drug response status and to risk for NAFE. RESULTS: We found no gene or gene set that reached genome-wide significance. Yet, we identified several prospective candidate genes - among them DEPDC5, which showed a potential association with resistance to ASMs. We found some evidence for an enrichment of truncating variants in dominant familial NAFE genes in our cohort of non-familial NAFE and in association with drug-resistant NAFE. INTERPRETATION: Our study identifies potential candidate genes for ASM resistance. Our results corroborate the role of rare variants for non-familial NAFE and imply their involvement in drug-resistant epilepsy. Future large-scale genetic research studies are needed to substantiate these findings

    A genome-wide association study of sodium levels and drug metabolism in an epilepsy cohort treated with carbamazepine and oxcarbazepine

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    Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy. Objective: To ascertain the clinical and genetic factors contributing to carbamazepine- and oxcarbazepine-induced hyponatremia (COIH), and to carbamazepine (CBZ) metabolism, in a retrospectively collected, cross-sectional cohort of people with epilepsy. Methods: We collected data on serum sodium levels and antiepileptic drug levels in people with epilepsy attending a tertiary epilepsy center while on treatment with CBZ or OXC. We defined hyponatremia as Na+ ≀134 mEq/L. We estimated the CBZ metabolic ratio defined as the log transformation of the ratio of metabolite CBZ-diol to unchanged drug precursor substrate as measured in serum. Results: Clinical and genetic data relating to carbamazepine and oxcarbazepine trials were collected in 1141 patients. We did not observe any genome-wide significant associations with sodium level in a linear trend or hyponatremia as a dichotomous trait. Age, sex, number of comedications, phenytoin use, phenobarbital use, and sodium valproate use were significant predictors of CBZ metabolic ratio. No genome-wide significant associations with CBZ metabolic ratio were found. Significance: Although we did not detect a genetic predictor of hyponatremia or CBZ metabolism in our cohort, our findings suggest that the determinants of CBZ metabolism are multifactorial
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