Bioinformatics advances in saliva diagnostics

There is a need recognized by the National Institute of Dental & Craniofacial Research and the National Cancer Institute to advance basic, translational and clinical saliva research. The goal of the Salivaomics Knowledge Base (SKB) is to create a data management system and web resource constructed to support human salivaomics research. To maximize the utility of the SKB for retrieval, integration and analysis of data, we have developed the Saliva Ontology and SDxMart. This article reviews the informatics advances in saliva diagnostics made possible by the Saliva Ontology and SDxMart

BioMart: a data federation framework for large collaborative projects

BioMart is a freely available, open source, federated database system that provides a unified access to disparate, geographically distributed data sources. It is designed to be data agnostic and platform independent, such that existing databases can easily be incorporated into the BioMart framework. BioMart allows databases hosted on different servers to be presented seamlessly to users, facilitating collaborative projects between different research groups. BioMart contains several levels of query optimization to efficiently manage large data sets and offers a diverse selection of graphical user interfaces and application programming interfaces to ensure that queries can be performed in whatever manner is most convenient for the user. The software has now been adopted by a large number of different biological databases spanning a wide range of data types and providing a rich source of annotation available to bioinformaticians and biologists alike

Unilateral thalamic infarction presenting as vertical gaze palsy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Vertical gaze palsy is a recognized manifestation of midbrain lesions. It rarely is a consequence of unilateral thalamic infarction.</p> <p>Case presentation</p> <p>We report the case of a 48-year-old African-American woman who presented to our facility with vertical gaze palsy and evidence of left medial thalamic infarct on diffusion-weighted imaging without coexisting midbrain ischemia. The etiology of infarct was determined to be small vessel disease after extensive investigation.</p> <p>Conclusions</p> <p>This report suggests a possible role of the thalamus as a vertical gaze control center. Clinicoradiological studies are needed to further define the role of the thalamus in vertical gaze control.</p

Enhanced cosmic-ray flux toward zeta Persei inferred from laboratory study of H3+ - e- recombination rate

The H3+ molecular ion plays a fundamental role in interstellar chemistry, as it initiates a network of chemical reactions that produce many interstellar molecules. In dense clouds, the H3+ abundance is understood using a simple chemical model, from which observations of H3+ yield valuable estimates of cloud path length, density, and temperature. On the other hand, observations of diffuse clouds have suggested that H3+ is considerably more abundant than expected from the chemical models. However, diffuse cloud models have been hampered by the uncertain values of three key parameters: the rate of H3+ destruction by electrons, the electron fraction, and the cosmic-ray ionisation rate. Here we report a direct experimental measurement of the H3+ destruction rate under nearly interstellar conditions. We also report the observation of H3+ in a diffuse cloud (towards zeta Persei) where the electron fraction is already known. Taken together, these results allow us to derive the value of the third uncertain model parameter: we find that the cosmic-ray ionisation rate in this sightline is forty times faster than previously assumed. If such a high cosmic-ray flux is indeed ubiquitous in diffuse clouds, the discrepancy between chemical models and the previous observations of H3+ can be resolved.Comment: 6 pages, Nature, in pres

Radiative association and inverse predissociation of oxygen atoms

The formation of \mbox{O}_2 by radiative association and by inverse predissociation of ground state oxygen atoms is studied using quantum-mechanical methods. Cross sections, emission spectra, and rate coefficients are presented and compared with prior experimental and theoretical results. At temperatures below 1000~K radiative association occurs by approach along the $1\,{}^3\Pi_u$ state of \mbox{O}_2 and above 1000~K inverse predissociation through the \mbox{B}\,{}^3\Sigma_u^- state is the dominant mechanism. This conclusion is supported by a quantitative comparison between the calculations and data obtained from hot oxygen plasma spectroscopy.Comment: submitted to Phys. Rev. A (Sept. 7., 1994), 19 pages, 4 figures, latex (revtex3.0 and epsf.sty

A remote secondary binding pocket promotes heteromultivalent targeting of DC-SIGN

Dendritic cells (DC) are antigen-presenting cells coordinating the interplay of the innate and the adaptive immune response. The endocytic C-type lectin receptors DC-SIGN and Langerin display expression profiles restricted to distinct DC subtypes and have emerged as prime targets for next-generation immunotherapies and anti-infectives. Using heteromultivalent liposomes copresenting mannosides bearing aromatic aglycones with natural glycan ligands, we serendipitously discovered striking cooperativity effects for DC-SIGN+ but not for Langerin+ cell lines. Mechanistic investigations combining NMR spectroscopy with molecular docking and molecular dynamics simulations led to the identification of a secondary binding pocket for the glycomimetics. This pocket, located remotely of DC-SIGN’s carbohydrate bindings site, can be leveraged by heteromultivalent avidity enhancement. We further present preliminary evidence that the aglycone allosterically activates glycan recognition and thereby contributes to DC-SIGN-specific cell targeting. Our findings have important implications for both translational and basic glycoscience, showcasing heteromultivalent targeting of DCs to improve specificity and supporting potential allosteric regulation of DC-SIGN and CLRs in general

Detection of very high energy gamma-ray emission from the gravitationally-lensed blazar QSO B0218+357 with the MAGIC telescopes

Context. QSO B0218+357 is a gravitationally lensed blazar located at a redshift of 0.944. The gravitational lensing splits the emitted radiation into two components, spatially indistinguishable by gamma-ray instruments, but separated by a 10-12 day delay. In July 2014, QSO B0218+357 experienced a violent flare observed by the Fermi-LAT and followed by the MAGIC telescopes. Aims. The spectral energy distribution of QSO B0218+357 can give information on the energetics of z ~ 1 very high energy gamma- ray sources. Moreover the gamma-ray emission can also be used as a probe of the extragalactic background light at z ~ 1. Methods. MAGIC performed observations of QSO B0218+357 during the expected arrival time of the delayed component of the emission. The MAGIC and Fermi-LAT observations were accompanied by quasi-simultaneous optical data from the KVA telescope and X-ray observations by Swift-XRT. We construct a multiwavelength spectral energy distribution of QSO B0218+357 and use it to model the source. The GeV and sub-TeV data, obtained by Fermi-LAT and MAGIC, are used to set constraints on the extragalactic background light. Results. Very high energy gamma-ray emission was detected from the direction of QSO B0218+357 by the MAGIC telescopes during the expected time of arrival of the trailing component of the flare, making it the farthest very high energy gamma-ray sources detected to date. The observed emission spans the energy range from 65 to 175 GeV. The combined MAGIC and Fermi-LAT spectral energy distribution of QSO B0218+357 is consistent with current extragalactic background light models. The broad band emission can be modeled in the framework of a two zone external Compton scenario, where the GeV emission comes from an emission region in the jet, located outside the broad line region.Comment: 11 pages, 6 figures, accepted for publication in A&

Limits to dark matter annihilation cross-section from a combined analysis of MAGIC and Fermi-LAT observations of dwarf satellite galaxies

We present the first joint analysis of gamma-ray data from the MAGIC Cherenkov telescopes and the Fermi Large Area Telescope (LAT) to search for gamma-ray signals from dark matter annihilation in dwarf satellite galaxies. We combine 158 hours of Segue 1 observations with MAGIC with 6-year observations of 15 dwarf satellite galaxies by the Fermi-LAT. We obtain limits on the annihilation cross-section for dark matter particle masses between 10 GeV and 100 TeV - the widest mass range ever explored by a single gamma-ray analysis. These limits improve on previously published Fermi-LAT and MAGIC results by up to a factor of two at certain masses. Our new inclusive analysis approach is completely generic and can be used to perform a global, sensitivity-optimized dark matter search by combining data from present and future gamma-ray and neutrino detectors.Comment: 19 pages, 3 figures. V2: Few typos corrected and references added. Matches published version JCAP 02 (2016) 03