2,687 research outputs found

    Rigidity of SU(2,2|2)-symmetric solutions in Type IIB

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    We investigate the existence of half-BPS solutions in Type IIB supergravity which are invariant under the superalgebra SU(2,2|2) realized on either AdS_5 x S^2 x S^1 or AdS_5 x S^3 warped over a Riemann surface \Sigma with boundary. We prove that, in both cases, the only solution is AdS_5 x S^5 itself. We argue that this result provides evidence for the non-existence of fully back-reacted intersecting D3/D7 branes with either AdS_5 x S^2 x S^1 x \Sigma or AdS_5 x S^3 x \Sigma near-horizon limits.Comment: 55 page

    Digital PCR methods improve detection sensitivity and measurement precision of low abundance mtDNA deletions

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    Mitochondrial DNA (mtDNA) mutations are a common cause of primary mitochondrial disorders, and have also been implicated in a broad collection of conditions, including aging, neurodegeneration, and cancer. Prevalent among these pathogenic variants are mtDNA deletions, which show a strong bias for the loss of sequence in the major arc between, but not including, the heavy and light strand origins of replication. Because individual mtDNA deletions can accumulate focally, occur with multiple mixed breakpoints, and in the presence of normal mtDNA sequences, methods that detect broad-spectrum mutations with enhanced sensitivity and limited costs have both research and clinical applications. In this study, we evaluated semi-quantitative and digital PCR-based methods of mtDNA deletion detection using double-stranded reference templates or biological samples. Our aim was to describe key experimental assay parameters that will enable the analysis of low levels or small differences in mtDNA deletion load during disease progression, with limited false-positive detection. We determined that the digital PCR method significantly improved mtDNA deletion detection sensitivity through absolute quantitation, improved precision and reduced assay standard error

    Influenza C virus NS1 protein counteracts RIG-I-mediated IFN signalling

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    The nonstructural proteins 1 (NS1) from influenza A and B viruses are known as the main viral factors antagonising the cellular interferon (IFN) response, inter alia by inhibiting the retinoic acid-inducible gene I (RIG-I) signalling. The cytosolic pattern-recognition receptor RIG-I senses double-stranded RNA and 5'-triphosphate RNA produced during RNA virus infections. Binding to these ligands activates RIG-I and in turn the IFN signalling. We now report that the influenza C virus NS1 protein also inhibits the RIG-I-mediated IFN signalling. Employing luciferase-reporter assays, we show that expression of NS1-C proteins of virus strains C/JJ/50 and C/JHB/1/66 considerably reduced the IFN-β promoter activity. Mapping of the regions from NS1-C of both strains involved in IFN-β promoter inhibition showed that the N-terminal 49 amino acids are dispensable, while the C-terminus is required for proper modulation of the IFN response. When a mutant RIG-I, which is constitutively active without ligand binding, was employed, NS1-C still inhibited the downstream signalling, indicating that IFN inhibitory properties of NS1-C are not necessarily linked to an RNA binding mechanism

    Blow-up profile of rotating 2D focusing Bose gases

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    We consider the Gross-Pitaevskii equation describing an attractive Bose gas trapped to a quasi 2D layer by means of a purely harmonic potential, and which rotates at a fixed speed of rotation Ω\Omega. First we study the behavior of the ground state when the coupling constant approaches a_a\_* , the critical strength of the cubic nonlinearity for the focusing nonlinear Schr{\"o}dinger equation. We prove that blow-up always happens at the center of the trap, with the blow-up profile given by the Gagliardo-Nirenberg solution. In particular, the blow-up scenario is independent of Ω\Omega, to leading order. This generalizes results obtained by Guo and Seiringer (Lett. Math. Phys., 2014, vol. 104, p. 141--156) in the non-rotating case. In a second part we consider the many-particle Hamiltonian for NN bosons, interacting with a potential rescaled in the mean-field manner a_NN2β1w(Nβx),with--a\_N N^{2\beta--1} w(N^{\beta} x), with wapositivefunctionsuchthat a positive function such that \int\_{\mathbb{R}^2} w(x) dx = 1.Assumingthat. Assuming that \beta < 1/2andthat and that a\_N \to a\_*sufficientlyslowly,weprovethatthemanybodysystemisfullycondensedontheGrossPitaevskiigroundstateinthelimit sufficiently slowly, we prove that the many-body system is fully condensed on the Gross-Pitaevskii ground state in the limit N \to \infty$

    Cavitation of Electrons Bubbles in Liquid Helium Below saturation Pressure

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    We have used a Hartree-type electron-helium potential together with a density functional description of liquid 4^4He and 3^3He to study the explosion of electron bubbles submitted to a negative pressure. The critical pressure at which bubbles explode has been determined as a function of temperature. It has been found that this critical pressure is very close to the pressure at which liquid helium becomes globally unstable in the presence of electrons. It is shown that at high temperatures the capillary model overestimates the critical pressures. We have checked that a commonly used and rather simple electron-helium interaction yields results very similar to those obtained using the more accurate Hartree-type interaction. We have estimated that the crossover temperature for thermal to quantum nucleation of electron bubbles is very low, of the order of 6 mK for 4^4He.Comment: 22 pages, 9 figure

    Unique and conserved MicroRNAs in wheat chromosome 5D revealed by next-generation sequencing

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    MicroRNAs are a class of short, non-coding, single-stranded RNAs that act as post-transcriptional regulators in gene expression. miRNA analysis of Triticum aestivum chromosome 5D was performed on 454 GS FLX Titanium sequences of flow sorted chromosome 5D with a total of 3,208,630 good quality reads representing 1.34x and 1.61x coverage of the short (5DS) and long (5DL) arms of the chromosome respectively. In silico and structural analyses revealed a total of 55 miRNAs; 48 and 42 miRNAs were found to be present on 5DL and 5DS respectively, of which 35 were common to both chromosome arms, while 13 miRNAs were specific to 5DL and 7 miRNAs were specific to 5DS. In total, 14 of the predicted miRNAs were identified in wheat for the first time. Representation (the copy number of each miRNA) was also found to be higher in 5DL (1,949) compared to 5DS (1,191). Targets were predicted for each miRNA, while expression analysis gave evidence of expression for 6 out of 55 miRNAs. Occurrences of the same miRNAs were also found in Brachypodium distachyon and Oryza sativa genome sequences to identify syntenic miRNA coding sequences. Based on this analysis, two other miRNAs: miR1133 and miR167 were detected in B. distachyon syntenic region of wheat 5DS. Five of the predicted miRNA coding regions (miR6220, miR5070, miR169, miR5085, miR2118) were experimentally verified to be located to the 5D chromosome and three of them : miR2118, miR169 and miR5085, were shown to be 5D specific. Furthermore miR2118 was shown to be expressed in Chinese Spring adult leaves. miRNA genes identified in this study will expand our understanding of gene regulation in bread wheat

    Non-structural protein 1 of avian influenza A viruses differentially inhibit NF-κB promoter activation

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    <p>Abstract</p> <p>Background</p> <p>Influenza virus infection activates NF-κB and is a general prerequisite for a productive influenza virus infection. On the other hand, non-structural protein 1 (NS1) suppresses this viral activated NF-κB, presumably to prevent expression of NF-κB mediated anti-viral response. NS1 proteins of influenza A viruses are divided into two groups, known as allele A and allele B. The possible functional relevance of this NS1 division to viral pathogenicity is lacking.</p> <p>Findings</p> <p>The ability of NS1 protein from two avian influenza subtypes, H6N8 and H4N6, to inhibit NF-κB promoter activation was assessed. Further, efforts were made to characterize the genetic basis of this inhibition. We found that allele A NS1 proteins of H6N8 and H4N6 are significantly better in preventing dsRNA induced NF-κB promoter activation compared to allele B of corresponding subtypes, in a species independent manner. Furthermore, the ability to suppress NF-κB promoter activation was mapped to the effector domain while the RNA binding domain alone was unable to suppress this activation. Chimeric NS1 proteins containing either RNA binding domain of allele A and effector domain of allele B or vice versa, were equally potent in preventing NF-κB promoter activation compared to their wt. NS1 protein of allele A and B from both subtypes expressed efficiently as detected by Western blotting and predominantly localized in the nucleus in both A549 and MiLu cells as shown by <it>in situ </it>PLA.</p> <p>Conclusions</p> <p>Here, we present another aspect of NS1 protein in inhibiting dsRNA induced NF-κB activation in an allele dependent manner. This suggests a possible correlation with the virus's pathogenic potential.</p

    Left-handed color-sextet diquark in Kaon system

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    We investigate whether a color-sextet scalar diquark (H6{\bf H}_6) coupling to the left-handed quarks contributes to the ΔS=2\Delta S=2 process. It is found that the box diagrams mediated by WW and H6{\bf H}_6 bosons have no contributions to ΔS=2\Delta S=2 when the limit of mt=0m_t=0 is used, and the flavor mixing matrices for diagonalizing quark mass matrices are introduced at the same time. When the heavy top-quark mass effects are taken into account, it is found that in addition to the WH6W-{\bf H}_6 box diagrams significantly contributing to ΔS=2\Delta S=2, their effects can be as large as those from the H6H6{\bf H}_6-{\bf H}_6 box diagrams. Using the parameters that are constrained by the K0Kˉ0K^0-\bar K^0 mixing parameter ΔMK\Delta M_K and the Kaon indirect CP violation ϵK\epsilon_K, we find that the left-handed color-sextet diquark can lead to the Kaon direct CP violation being Re(ϵ/ϵ)0.4×103Re(\epsilon'/\epsilon) \sim 0.4 \times 10^{-3}. In the chosen scheme, although the diquark contribution to KLπ0ννˉK_L\to \pi^0 \nu \bar\nu is small, the branching ratio of K+π+ννˉK^+ \to \pi^+ \nu \bar\nu can reach the current experimental upper bound.Comment: 22 pages, 6 figure

    Underestimated Effect Sizes in GWAS: Fundamental Limitations of Single SNP Analysis for Dichotomous Phenotypes

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    Complex diseases are often highly heritable. However, for many complex traits only a small proportion of the heritability can be explained by observed genetic variants in traditional genome-wide association (GWA) studies. Moreover, for some of those traits few significant SNPs have been identified. Single SNP association methods test for association at a single SNP, ignoring the effect of other SNPs. We show using a simple multi-locus odds model of complex disease that moderate to large effect sizes of causal variants may be estimated as relatively small effect sizes in single SNP association testing. This underestimation effect is most severe for diseases influenced by numerous risk variants. We relate the underestimation effect to the concept of non-collapsibility found in the statistics literature. As described, continuous phenotypes generated with linear genetic models are not affected by this underestimation effect. Since many GWA studies apply single SNP analysis to dichotomous phenotypes, previously reported results potentially underestimate true effect sizes, thereby impeding identification of true effect SNPs. Therefore, when a multi-locus model of disease risk is assumed, a multi SNP analysis may be more appropriate
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