633 research outputs found

    Acute spontaneously resolving pulmonary vasculitis: a case report

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    This is the first description that we are aware of describing the spontaneous resolution of an acute pulmonary vasculitis, possibly secondary to microscopic polyangiitis. Haemoptysis is a common symptom for patients presenting to primary and tertiary referral centres, and pulmonary vasculitis is one of a variety of aetiologies that should always be considered. The pulmonary vasculitides are difficult diagnostic and management problems. They are encumbered by a relative paucity of level 1 evidence addressing their diagnosis, classification, and treatment. This is therefore an important paper to publish because it adds to the global breadth of experience with this important clinical condition.James B. Geake, and Graeme Maguir

    Combining machine learning with structurebased protein design to predict and engineer post-Translational modifications of proteins

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    Post-Translational modifications (PTMs) of proteins play a vital role in their function and stability. These modifications influence protein folding, signaling, protein-protein interactions, enzyme activity, binding affinity, aggregation, degradation, and much more. To date, over 400 types of PTMs have been described, representing chemical diversity well beyond the genetically encoded amino acids. Such modifications pose a challenge to the successful design of proteins, but also represent a major opportunity to diversify the protein engineering toolbox. To this end, we first trained artificial neural networks (ANNs) to predict eighteen of the most abundant PTMs, including protein glycosylation, phosphorylation, methylation, and deamidation. In a second step, these models were implemented inside the computational protein modeling suite Rosetta, which allows flexible combination with existing protocols to model the modified sites and understand their impact on protein stability as well as function. Lastly, we developed a new design protocol that either maximizes or minimizes the predicted probability of a particular site being modified. We find that this combination of ANN prediction and structure-based design can enable the modification of existing, as well as the introduction of novel, PTMs. The potential applications of our work include, but are not limited to, glycan masking of epitopes, strengthening protein-protein interactions through phosphorylation, as well as protecting proteins from deamidation liabilities. These applications are especially important for the design of new protein therapeutics where PTMs can drastically change the therapeutic properties of a protein. Our work adds novel tools to Rosetta s protein engineering toolbox that allow for the rational design of PTMs

    BAs and boride III-V alloys

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    Boron arsenide, the typically-ignored member of the III-V arsenide series BAs-AlAs-GaAs-InAs is found to resemble silicon electronically: its Gamma conduction band minimum is p-like (Gamma_15), not s-like (Gamma_1c), it has an X_1c-like indirect band gap, and its bond charge is distributed almost equally on the two atoms in the unit cell, exhibiting nearly perfect covalency. The reasons for these are tracked down to the anomalously low atomic p orbital energy in the boron and to the unusually strong s-s repulsion in BAs relative to most other III-V compounds. We find unexpected valence band offsets of BAs with respect to GaAs and AlAs. The valence band maximum (VBM) of BAs is significantly higher than that of AlAs, despite the much smaller bond length of BAs, and the VBM of GaAs is only slightly higher than in BAs. These effects result from the unusually strong mixing of the cation and anion states at the VBM. For the BAs-GaAs alloys, we find (i) a relatively small (~3.5 eV) and composition-independent band gap bowing. This means that while addition of small amounts of nitrogen to GaAs lowers the gap, addition of small amounts of boron to GaAs raises the gap (ii) boron ``semi-localized'' states in the conduction band (similar to those in GaN-GaAs alloys), and (iii) bulk mixing enthalpies which are smaller than in GaN-GaAs alloys. The unique features of boride III-V alloys offer new opportunities in band gap engineering.Comment: 18 pages, 14 figures, 6 tables, 61 references. Accepted for publication in Phys. Rev. B. Scheduled to appear Oct. 15 200

    The PHENIX Experiment at RHIC

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    The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix
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