34 research outputs found

    Strings between branes

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    D-brane configurations containing fundamental strings are constructed as classical solutions of Yang-Mills theory. The fundamental strings in these systems stretch between D-branes. In the case of D1-branes, this construction gives smooth (classical) resolutions of string junctions and string networks. Using a non-abelian Yang-Mills analysis of the string current, the string charge density is computed and is shown to have support in the region between the D-brane world-volumes. The 't Hooft-Polyakov monopole is analyzed using similar methods, and is shown to contain D-strings whose flux has support off the D-brane world-volume defined by the Higgs scalar field, when this field is interpreted in terms of a transverse dimension. The constructions presented here are used to give a qualitative picture of tachyon condensation in the Yang-Mills limit, where fundamental strings and lower-dimensional D-branes arise in a volume of space-time where brane-antibrane annihilation has occurred.Comment: 35 pages, 16 eps figures, JHEP style; v2: a comment adde

    Freedom and constraints in the K3 landscape

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    We consider ``magnetized brane'' compactifications of the type I/heterotic string on K3 with U(1) background fluxes. The gauge group and matter content of the resulting six-dimensional vacua are parameterized by a matrix encoding a lattice contained within the even, self-dual lattice Γ[superscript 3,19]. Mathematical results of Nikulin on lattice embeddings make possible a simple classification of all such solutions. We find that every six-dimensional theory parameterized in this way by a negative semi-definite matrix whose trace satisfies a simple tadpole constraint can be realized as a K3 compactification. This approach makes it possible to explicitly and efficiently construct all models in this class with any particular allowed gauge group and matter content, so that one can immediately ``dial-a-model'' with desired properties

    Using symptom-based case predictions to identify host genetic factors that contribute to COVID-19 susceptibility

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    Epidemiological and genetic studies on COVID-19 are currently hindered by inconsistent and limited testing policies to confirm SARS-CoV-2 infection. Recently, it was shown that it is possible to predict COVID-19 cases using cross-sectional self-reported disease-related symptoms. Here, we demonstrate that this COVID-19 prediction model has reasonable and consistent performance across multiple independent cohorts and that our attempt to improve upon this model did not result in improved predictions. Using the existing COVID-19 prediction model, we then conducted a GWAS on the predicted phenotype using a total of 1,865 predicted cases and 29,174 controls. While we did not find any common, large-effect variants that reached genome-wide significance, we do observe suggestive genetic associations at two SNPs (rs11844522, p = 1.9x10-7; rs5798227, p = 2.2x10-7). Explorative analyses furthermore suggest that genetic variants associated with other viral infectious diseases do not overlap with COVID-19 susceptibility and that severity of COVID-19 may have a different genetic architecture compared to COVID-19 susceptibility. This study represents a first effort that uses a symptom-based predicted phenotype as a proxy for COVID-19 in our pursuit of understanding the genetic susceptibility of the disease. We conclude that the inclusion of symptom-based predicted cases could be a useful strategy in a scenario of limited testing, either during the current COVID-19 pandemic or any future viral outbreak

    A2ML1 and otitis media: novel variants, differential expression, and relevant pathways

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    A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media

    Consensus recommendations for histological criteria of autoimmune hepatitis from the International AIH Pathology Group : Results of a workshop on AIH histology hosted by the European Reference Network on Hepatological Diseases and the European Society of Pathology

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    Background & Aims: Diagnostic histological criteria for autoimmune hepatitis (AIH) have not been clearly established. Previously published criteria focused mainly on chronic AIH, in which inflammatory changes mainly occur in portal/periportal regions and may not be applicable to acute presentation of AIH, in which inflammatory changes are typically predominantly lobular in location. International consensus criteria for the diagnosis and assessment of disease severity in both acute and chronic AIH are thus urgently needed. Methods: Seventeen expert liver pathologists convened at an international workshop and subsequently used a modified Delphi panel approach to establish consensus criteria for the histopathological diagnosis of AIH. Results: The consensus view is that liver biopsy should remain standard for diagnosing AIH. AIH is considered likely, if there is a predominantly portal lymphoplasmacytic hepatitis with more than mild interface activity and/or more than mild lobular hepatitis in the absence of histological features suggestive of another liver disease. AIH is also considered likely if there is predominantly lobular hepatitis with or without centrilobular necroinflammation and at least one of the following features: portal lymphoplasmacytic hepatitis, interface hepatitis or portal-based fibrosis, in the absence of histological features suggestive of another liver disease. Emperipolesis and hepatocellular rosettes are not regarded as being specific for AIH. Conclusions: The criteria proposed in this consensus statement provide a uniform approach to the histological diagnosis of AIH, which is relevant for patients with an acute as well as a chronic presentation and to more accurately reflect the current understanding of liver pathology in AIH. © 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Lt
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