35 research outputs found

    Minimal immersions of closed surfaces in hyperbolic three-manifolds

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    We study minimal immersions of closed surfaces (of genus g≥2g \ge 2) in hyperbolic 3-manifolds, with prescribed data (σ,tα)(\sigma, t\alpha), where σ\sigma is a conformal structure on a topological surface SS, and αdz2\alpha dz^2 is a holomorphic quadratic differential on the surface (S,σ)(S,\sigma). We show that, for each t∈(0,τ0)t \in (0,\tau_0) for some τ0>0\tau_0 > 0, depending only on (σ,α)(\sigma, \alpha), there are at least two minimal immersions of closed surface of prescribed second fundamental form Re(tα)Re(t\alpha) in the conformal structure σ\sigma. Moreover, for tt sufficiently large, there exists no such minimal immersion. Asymptotically, as t→0t \to 0, the principal curvatures of one minimal immersion tend to zero, while the intrinsic curvatures of the other blow up in magnitude.Comment: 16 page

    Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD

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    OBJECTIVE: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. METHODS: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. RESULTS: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. CONCLUSION: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD

    Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

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    Publisher Copyright: © 2019, The Author(s).Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.Peer reviewe
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