305 research outputs found

    The Open Navigation Surface Project

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    Many hydrographic and oceanographic agencies have moved or are moving towards gridded bathymetric products. However, there is no accepted format to allow these grids to be exchanged while maintaining data and metadata integrity. This paper describes the Open Navigation Surface (ONS) Project, which aims to fill this gap. The ONS Project is an open-source software project designed to provide a freely available, portable source-code library to encapsulate gridded bathymetric surfaces with associated uncertainty values. The data file format is called a Bathymetric Attributed Grid (BAG). The BAG is developed and maintained by the ONS Working Group (ONSWG), and the source code is available via the ONS websit

    Jost Functions and Jost Solutions for Jacobi Matrices, I. A Necessary and Sufficient Condition for Szego Asymptotics

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    We provide necessary and sufficient conditions for a Jacobi matrix to produce orthogonal polynomials with Szeg\H{o} asymptotics off the real axis. A key idea is to prove the equivalence of Szeg\H{o} asymptotics and of Jost asymptotics for the Jost solution. We also prove L2L^2 convergence of Szeg\H{o} asymptotics on the spectrum.Comment: 49 page

    The Open Navigation Surface Project

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    Many hydrographic and oceanographic agencies have moved or are moving towards gridded bathymetric products. However, there is no accepted format to allow these grids to be exchanged while maintaining data and metadata integrity. This paper describes the Open Navigation Surface (ONS) Project, which aims to fill this gap. The ONS Project is an open-source software project designed to provide a freely available, portable source-code library to encapsulate gridded bathymetric surfaces with associated uncertainty values. The data file format is called a Bathymetric Attributed Grid (BAG). The BAG is developed and maintained by the ONS Working Group (ONSWG), and the source code is available via the ONS website.Muchas agencies hidrogrâficas y oceanogrâficas se han orientado o se estân orientando hacia los productos batimétricos cuadriculados. Sin embargo, no existe un formato aceptado para que estas cuadricuias sean intercambiadas manteniendo la integridad de los datos y los meta datos. Este articulo describe el Proyecto « Superficie de Navegaciôn Abierta » (ONS) cuyo objeto es cubrir este vacio. El proyecto ONS es un proyecto de software de fuente abierta disehado para proveer una biblioteca portâtil de côdigo fuente de libre disponibilidad para encapsular superficies batimétricas cuadriculadas con sus valores de incertidumbre asociados. El formato de archivo de datos es llamado Cuadricula Batimétrica Tributada (BAG). El BAG es desarrollado y mantenido por el Grupo de Trabajo ONS (ONSWG), y el côdigo fuente es disponible a través de sitio web de ONS.De nombreuses agences hydrographiques et océanographiques se sont orientées ou s ’orientent actuellement vers les produits bathymétriques quadrillés. Toutefois, il n'existe pas de format accepté qui permette à ces quadrillages d'être échangés tout en conservant l’intégrité des données et des métadonnées. Le présent article décrit le projet ONS (Open Navigation Surface) qui vise à combler cette lacune. Le projet ONS est un projet de logiciel libre conçu pour fournir une bibliothèque portable de code source à libre disponibilité devant encapsuler des surfaces bathymétriques maillées avec des valeurs d'incertitude associées. Le format du fichier des données est appelé Carroyage bathymétrique attribué (BAG). Le BAG est développé est tenu à jour par le groupe de travail ONS et le code source est disponible sur le site Web ONS

    The relation between global migration and trade networks

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    In this paper we develop a methodology to analyze and compare multiple global networks, focusing our analysis on the relation between human migration and trade. First, we identify the subset of products for which the presence of a community of migrants significantly increases trade intensity, where to assure comparability across networks we apply a hypergeometric filter that lets us identify those links which intensity is significantly higher than expected. Next, proposing a new way to define country neighbors based on the most intense links in the trade network, we use spatial econometrics techniques to measure the effect of migration on international trade, while controlling for network interdependences. Overall, we find that migration significantly boosts trade across countries and we are able to identify product categories for which this effect is particularly strong

    The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans

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    <p>Abstract</p> <p>Background</p> <p>Arachidonic acid (AA) is a long-chain omega-6 polyunsaturated fatty acid (PUFA) synthesized from the precursor dihomo-gamma-linolenic acid (DGLA) that plays a vital role in immunity and inflammation. Variants in the Fatty Acid Desaturase (<it>FADS</it>) family of genes on chromosome 11q have been shown to play a role in PUFA metabolism in populations of European and Asian ancestry; no work has been done in populations of African ancestry to date.</p> <p>Results</p> <p>In this study, we report that African Americans have significantly higher circulating levels of plasma AA (p = 1.35 × 10<sup>-48</sup>) and lower DGLA levels (p = 9.80 × 10<sup>-11</sup>) than European Americans. Tests for association in N = 329 individuals across 80 nucleotide polymorphisms (SNPs) in the Fatty Acid Desaturase (<it>FADS</it>) locus revealed significant association with AA, DGLA and the AA/DGLA ratio, a measure of enzymatic efficiency, in both racial groups (peak signal p = 2.85 × 10<sup>-16 </sup>in African Americans, 2.68 × 10<sup>-23 </sup>in European Americans). Ancestry-related differences were observed at an upstream marker previously associated with AA levels (rs174537), wherein, 79-82% of African Americans carry two copies of the G allele compared to only 42-45% of European Americans. Importantly, the allelic effect of the G allele, which is associated with <it>enhanced </it>conversion of DGLA to AA, on enzymatic efficiency was similar in both groups.</p> <p>Conclusions</p> <p>We conclude that the impact of <it>FADS </it>genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to the larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA.</p

    Eggshell membrane in the treatment of pain and stiffness from osteoarthritis of the knee: a randomized, multicenter, double-blind, placebo-controlled clinical study

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    Natural Eggshell Membrane (NEM®) is a new novel dietary supplement that contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy articular cartilage and the surrounding synovium. The randomized, multicenter, double-blind, placebo-controlled Osteoarthritis Pain Treatment Incorporating NEM® clinical study was conducted to evaluate the efficacy and safety of NEM® as a treatment for pain and stiffness associated with osteoarthritis of the knee. Sixty-seven patients were randomly assigned to receive either oral NEM® 500 mg (n = 34) or placebo (n = 33) daily for 8 weeks. The primary endpoint was the change in overall Western Ontario and McMasters Universities (WOMAC) Osteoarthritis Index as well as pain, stiffness, and function WOMAC subscales measured at 10, 30, and 60 days. The clinical assessment was performed on the intent-to-treat population. Supplementation with NEM® produced an absolute rate of response that was statistically significant (up to 26.6%) versus placebo at all time points for both pain and stiffness, but was not significantly improved for function and overall WOMAC scores, although trending toward improvement. Rapid responses were seen for mean pain subscores (15.9% reduction, P = 0.036) and mean stiffness subscores (12.8% reduction, P = 0.024) occurring after only 10 days of supplementation. There were no serious adverse events reported during the study and the treatment was reported to be well tolerated by study participants. Natural Eggshell Membrane (NEM®) is an effective and safe option for the treatment of pain and stiffness associated with knee osteoarthritis. Supplementation with NEM®, 500 mg taken once daily, significantly reduced both joint pain and stiffness compared to placebo at 10, 30, and 60 days. The Clinical Trial Registration number for this study is NCT00750477

    Ras Conformational Switching: Simulating Nucleotide-Dependent Conformational Transitions with Accelerated Molecular Dynamics

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    Ras mediates signaling pathways controlling cell proliferation and development by cycling between GTP- and GDP-bound active and inactive conformational states. Understanding the complete reaction path of this conformational change and its intermediary structures is critical to understanding Ras signaling. We characterize nucleotide-dependent conformational transition using multiple-barrier-crossing accelerated molecular dynamics (aMD) simulations. These transitions, achieved for the first time for wild-type Ras, are impossible to observe with classical molecular dynamics (cMD) simulations due to the large energetic barrier between end states. Mapping the reaction path onto a conformer plot describing the distribution of the crystallographic structures enabled identification of highly populated intermediate structures. These structures have unique switch orientations (residues 25–40 and 57–75) intermediate between GTP and GDP states, or distinct loop3 (46–49), loop7 (105–110), and α5 C-terminus (159–166) conformations distal from the nucleotide-binding site. In addition, these barrier-crossing trajectories predict novel nucleotide-dependent correlated motions, including correlations of α2 (residues 66–74) with α3-loop7 (93–110), loop2 (26–37) with loop10 (145–151), and loop3 (46–49) with α5 (152–167). The interconversion between newly identified Ras conformations revealed by this study advances our mechanistic understanding of Ras function. In addition, the pattern of correlated motions provides new evidence for a dynamic linkage between the nucleotide-binding site and the membrane interacting C-terminus critical for the signaling function of Ras. Furthermore, normal mode analysis indicates that the dominant collective motion that occurs during nucleotide-dependent conformational exchange, and captured in aMD (but absent in cMD) simulations, is a low-frequency motion intrinsic to the structure

    Large-Scale Conformational Changes of Trypanosoma cruzi Proline Racemase Predicted by Accelerated Molecular Dynamics Simulation

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    Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is a life-threatening illness affecting 11–18 million people. Currently available treatments are limited, with unacceptable efficacy and safety profiles. Recent studies have revealed an essential T. cruzi proline racemase enzyme (TcPR) as an attractive candidate for improved chemotherapeutic intervention. Conformational changes associated with substrate binding to TcPR are believed to expose critical residues that elicit a host mitogenic B-cell response, a process contributing to parasite persistence and immune system evasion. Characterization of the conformational states of TcPR requires access to long-time-scale motions that are currently inaccessible by standard molecular dynamics simulations. Here we describe advanced accelerated molecular dynamics that extend the effective simulation time and capture large-scale motions of functional relevance. Conservation and fragment mapping analyses identified potential conformational epitopes located in the vicinity of newly identified transient binding pockets. The newly identified open TcPR conformations revealed by this study along with knowledge of the closed to open interconversion mechanism advances our understanding of TcPR function. The results and the strategy adopted in this work constitute an important step toward the rationalization of the molecular basis behind the mitogenic B-cell response of TcPR and provide new insights for future structure-based drug discovery
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