700 research outputs found

    Kahler Independence of the G2-MSSM

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    The G2-MSSM is a model of particle physics coupled to moduli fields with interesting phenomenology both for colliders and astrophysical experiments. In this paper we consider a more general model - whose moduli Kahler potential is a completely arbitrary G2-holonomy Kahler potential and whose matter Kahler potential is also more general. We prove that the vacuum structure and spectrum of BSM particles is largely unchanged in this much more general class of theories. In particular, gaugino masses are still supressed relative to the gravitino mass and moduli masses. We also consider the effects of higher order corrections to the matter Kahler potential and find a connection between the nature of the LSP and flavor effects.Comment: Final version, matches the version published in JHE

    Increased RPA1 gene dosage affects genomic stability potentially contributing to 17p13.3 duplication syndrome

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    A novel microduplication syndrome involving various-sized contiguous duplications in 17p13.3 has recently been described, suggesting that increased copy number of genes in 17p13.3, particularly PAFAH1B1, is associated with clinical features including facial dysmorphism, developmental delay, and autism spectrum disorder. We have previously shown that patient-derived cell lines from individuals with haploinsufficiency of RPA1, a gene within 17p13.3, exhibit an impaired ATR-dependent DNA damage response (DDR). Here, we show that cell lines from patients with duplications specifically incorporating RPA1 exhibit a different although characteristic spectrum of DDR defects including abnormal S phase distribution, attenuated DNA double strand break (DSB)-induced RAD51 chromatin retention, elevated genomic instability, and increased sensitivity to DNA damaging agents. Using controlled conditional over-expression of RPA1 in a human model cell system, we also see attenuated DSB-induced RAD51 chromatin retention. Furthermore, we find that transient over-expression of RPA1 can impact on homologous recombination (HR) pathways following DSB formation, favouring engagement in aberrant forms of recombination and repair. Our data identifies unanticipated defects in the DDR associated with duplications in 17p13.3 in humans involving modest RPA1 over-expression

    Expedited batch processing and analysis of transposon insertions

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    <p>Abstract</p> <p>Background</p> <p>With advances in sequencing technology, greater and greater amounts of eukaryotic genome data are becoming available. Often, large portions of these genomes consist of transposable elements, frequently accounting for 50% or more in vertebrates. Each transposable element family may have thousands or tens of thousands of individual copies within a given genome, and therefore it can take an exorbitant amount of time and effort to process data in a meaningful fashion.</p> <p>Findings</p> <p>In order to combat this problem, we developed a set of bioinformatics techniques and programs to streamline the analysis. This includes a unique Perl script which automates the process of taking BLAST, Repeatmasker and similar data to extract and manipulate the hit sequences from the genome. This script, called Process_hits uses an object-oriented methodology to compile all hit locations from a given file for processing, organize this data into useable categories, and output it in multiple formats.</p> <p>Conclusions</p> <p>The program proved capable of handling large amounts of transposon data in an efficient fashion. It is equipped with a number of useful sub-functions, each of which is contained within its own sub-module to allow for greater expandability and as a foundation for future program design.</p

    T Cell Integrin Overexpression as a Model of Murine Autoimmunity

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    Integrin adhesion molecules have important adhesion and signaling functions. They also play a central role in the pathogenesis of many autoimmune diseases. Over the past few years we have described a T cell adoptive transfer model to investigate the role of T cell integrin adhesion molecules in the development of autoimmunity. This report summarizes the methods we used in establishing this murine model. By treating murine CD4+ T cells with DNA hypomethylating agents and by transfection we were able to test the in vitro effects of integrin overexpression on T cell autoreactive proliferation, cytotoxicity, adhesion and trafficking. Furthermore, we showed that the ability to induce in vivo autoimmunity may be unique to the integrin lymphocyte function associated antigen-1 (LFA-1)

    RNAcontext: A New Method for Learning the Sequence and Structure Binding Preferences of RNA-Binding Proteins

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    Metazoan genomes encode hundreds of RNA-binding proteins (RBPs). These proteins regulate post-transcriptional gene expression and have critical roles in numerous cellular processes including mRNA splicing, export, stability and translation. Despite their ubiquity and importance, the binding preferences for most RBPs are not well characterized. In vitro and in vivo studies, using affinity selection-based approaches, have successfully identified RNA sequence associated with specific RBPs; however, it is difficult to infer RBP sequence and structural preferences without specifically designed motif finding methods. In this study, we introduce a new motif-finding method, RNAcontext, designed to elucidate RBP-specific sequence and structural preferences with greater accuracy than existing approaches. We evaluated RNAcontext on recently published in vitro and in vivo RNA affinity selected data and demonstrate that RNAcontext identifies known binding preferences for several control proteins including HuR, PTB, and Vts1p and predicts new RNA structure preferences for SF2/ASF, RBM4, FUSIP1 and SLM2. The predicted preferences for SF2/ASF are consistent with its recently reported in vivo binding sites. RNAcontext is an accurate and efficient motif finding method ideally suited for using large-scale RNA-binding affinity datasets to determine the relative binding preferences of RBPs for a wide range of RNA sequences and structures

    Hypersensitivity Pneumonitis-like Granulomatous Lung Disease with Nontuberculous Mycobacteria from Exposure to Hot Water Aerosols

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    OBJECTIVE: Human activities associated with aerosol-generating hot water sources are increasingly popular. Recently, a hypersensitivity pneumonitis (HP)-like granulomatous lung disease, with non-tuberculous mycobacteria from exposure to hot water aerosols from hot tubs/spas, showers, and indoor swimming pools, has been described in immunocompetent individuals (also called “hot tub lung”). Our objective in this study was to examine four additional cases of hot tub lung and compare these cases with others reported in the English print literature on this disease. DATA SOURCES AND EXTRACTION: We retrospectively reviewed all cases (n = 4) of presumptively diagnosed hot tub lung in immunocompetent individuals at the various physician practices in Springfield, Illinois, during 2001–2005. In addition, we searched MEDLINE for cases of hot tub lung described in the literature. DATA SYNTHESIS: We summarized the clinical presentation and investigations of four presumptive cases and reviewed previously reported cases of hot tub lung. CONCLUSIONS: There is a debate in the literature whether hot tub lung is an HP or a direct infection of the lung by nontuberculous mycobacteria. Primary prevention of this disease relies on ventilation and good use practices. Secondary prevention of this disease requires education of both the general public and clinicians to allow for the early diagnosis of this disease

    Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.

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    Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses

    Aspects of Non-minimal Gauge Mediation

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    A large class of non-minimal gauge mediation models, such as (semi-)direct gauge mediation, predict a hierarchy between the masses of the supersymmetric standard model gauginos and those of scalar particles. We perform a comprehensive study of these non-minimal gauge mediation models, including mass calculations in semi-direct gauge mediation, to illustrate these features, and discuss the phenomenology of the models. We point out that the cosmological gravitino problem places stringent constraints on mass splittings, when the Bino is the NLSP. However, the GUT relation of the gaugino masses is broken unlike the case of minimal gauge mediation, and an NLSP other than the Bino (especially the gluino NLSP) becomes possible, relaxing the cosmological constraints. We also discuss the collider signals of the models.Comment: 56 pages, 8 figures; v2:minor corrections, references added; v3:minor correction

    MR and CT techniques

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    Magnetic resonance imaging (MRI) and computed tomography (CT) are routinely used in female pelvis imaging. MRI is primarily useful for locoregional characterization of benign and malignant diseases. CT is less accurate in locoregional evaluation, but remains useful in the follow-up of treated gynecological malignancies, as well as in the setting of emergency and in the guidance of biopsies. Although transabdominal and transvaginal ultrasonography (US) is not under the scope of this chapter, it remains the first-line imaging method for most gynecological conditions.info:eu-repo/semantics/publishedVersio
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