1,899 research outputs found

    Valve malfunction detection apparatus

    Get PDF
    A detection system is provided for sensing a malfunction of a valve having an outlet connected to an end of a first pipe through which pressurized fluid may be flowed in a downstream direction away from the valve. The system includes a bypass pipe connected at its opposite ends to the first pipe and operative to bypass a portion of the fluid flow therethrough around a predetermined section thereof. A housing is interiorly divided by a flexible diaphragm into first and second opposite chambers which are respectively communicated with the first pipe section and the bypass pipe, the diaphragm being spring-biased toward the second chamber. The diaphragm housing cooperates with check valves and orifices connected in the two pipes to create and maintain a negative pressure in the first pipe section in response to closure of the valve during pressurized flow through the first pipe. A pressure switch senses the negative pressure and transmits a signal indicative thereof to a computer. Upon cessation of the signal while the valve is still closed, the computer responsively generates a signal indicating that the valve, or another portion of the detection system, is leaking

    RCSB Protein Data Bank: visualizing groups of experimentally determined PDB structures alongside computed structure models of proteins

    Get PDF
    Recent advances in Artificial Intelligence and Machine Learning (e.g., AlphaFold, RosettaFold, and ESMFold) enable prediction of three-dimensional (3D) protein structures from amino acid sequences alone at accuracies comparable to lower-resolution experimental methods. These tools have been employed to predict structures across entire proteomes and the results of large-scale metagenomic sequence studies, yielding an exponential increase in available biomolecular 3D structural information. Given the enormous volume of this newly computed biostructure data, there is an urgent need for robust tools to manage, search, cluster, and visualize large collections of structures. Equally important is the capability to efficiently summarize and visualize metadata, biological/biochemical annotations, and structural features, particularly when working with vast numbers of protein structures of both experimental origin from the Protein Data Bank (PDB) and computationally-predicted models. Moreover, researchers require advanced visualization techniques that support interactive exploration of multiple sequences and structural alignments. This paper introduces a suite of tools provided on the RCSB PDB research-focused web portal RCSB. org, tailor-made for efficient management, search, organization, and visualization of this burgeoning corpus of 3D macromolecular structure data

    X-ray structures of two proteins belonging to Pfam DUF178 revealed unexpected structural similarity to the DUF191 Pfam family

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Pfam is a comprehensive collection of protein domains and families, with a range of well-established information including genome annotation. Pfam has two large series of functionally uncharacterized families, known as Domains of Unknown Function (DUFs) and Uncharacterized Protein Families (UPFs).</p> <p>Results</p> <p>Crystal structures of two proteins from <it>Deinococcus radiodurans </it>and <it>Streptomyces coelicolor </it>belonging to Pfam protein family DUF178 (ID: PF02621) have been determined using Selenium-Single-wavelength Anomalous Dispersion (Se-SAD). Based on the structure, we have identified the putative function for this family of protein.</p> <p>Conclusion</p> <p>Unexpectedly, we found that DUF178 Pfam is remarkably similar to Pfam family DUF191 suggesting that the sequence-based classification alone may not be sufficient to classify proteins into Pfam families.</p

    Higher physical fitness levels are associated with less language decline in healthy ageing

    Get PDF
    Healthy ageing is associated with decline in cognitive abilities such as language. Aerobic fitness has been shown to ameliorate decline in some cognitive domains, but the potential benefits for language have not been examined. In a cross-sectional sample, we investigated the relationship between aerobic fitness and tip-of-the-tongue states. These are among the most frequent cognitive failures in healthy older adults and occur when a speaker knows a word but is unable to produce it. We found that healthy older adults indeed experience more tip-of-the-tongue states than young adults. Importantly, higher aerobic fitness levels decrease the probability of experiencing tip-of-the-tongue states in healthy older adults. Fitness-related differences in word finding abilities are observed over and above effects of age. This is the first demonstration of a link between aerobic fitness and language functioning in healthy older adults

    Photometric and spectroscopic gamma-ray observations of solar transient phenomena using long duration balloons

    Get PDF
    A program currently in progress to conduct extended duration spectroscopic and photometric observation of solar X-ray phenomena from balloons is described. High photometric sensitivity to weak hard X-ray bursts is attained using a 600 sq cm array of phoswich scintillators. High spectral resolution for stronger bursts is available from an array of planar germanium detectors. These instruments are carried in a novel balloon gondola dssigned for the 15 to 20 day float durations available through using conventional zero pressure balloons in the radiation controlled (RACOON) mode

    Recognition of Polyadenylate RNA by the Poly(A)-Binding Protein

    Get PDF
    AbstractThe cocrystal structure of human poly(A)-binding protein (PABP) has been determined at 2.6 Å resolution. PABP recognizes the 3′ mRNA poly(A) tail and plays critical roles in eukaryotic translation initiation and mRNA stabilization/degradation. The minimal PABP used in this study consists of the N-terminal two RRM-type RNA-binding domains connected by a short linker (RRM1/2). These two RRMs form a continuous RNA-binding trough, lined by an antiparallel β sheet backed by four α helices. The polyadenylate RNA adopts an extended conformation running the length of the molecular trough. Adenine recognition is primarily mediated by contacts with conserved residues found in the RNP motifs of the two RRMs. The convex dorsum of RRM1/2 displays a phylogenetically conserved hydrophobic/acidic portion, which may interact with translation initiation factors and regulatory proteins

    Structural basis for activation of the therapeutic l-nucleoside analogs 3TC and troxacitabine by human deoxycytidine kinase

    Get PDF
    l-nucleoside analogs represent an important class of small molecules for treating both viral infections and cancers. These pro-drugs achieve pharmacological activity only after enzyme-catalyzed conversion to their tri-phosphorylated forms. Herein, we report the crystal structures of human deoxycytidine kinase (dCK) in complex with the l-nucleosides (−)-β-2′,3′-dideoxy-3′-thiacytidine (3TC)—an approved anti-human immunodeficiency virus (HIV) agent—and troxacitabine (TRO)—an experimental anti-neoplastic agent. The first step in activating these agents is catalyzed by dCK. Our studies reveal how dCK, which normally catalyzes phosphorylation of the natural d-nucleosides, can efficiently phosphorylate substrates with non-physiologic chirality. The capability of dCK to phosphorylate both d- and l-nucleosides and nucleoside analogs derives from structural properties of both the enzyme and the substrates themselves. First, the nucleoside-binding site tolerates substrates with different chiral configurations by maintaining virtually all of the protein-ligand interactions responsible for productive substrate positioning. Second, the pseudo-symmetry of nucleosides and nucleoside analogs in combination with their conformational flexibility allows the l- and d-enantiomeric forms to adopt similar shapes when bound to the enzyme. This is the first analysis of the structural basis for activation of l-nucleoside analogs, providing further impetus for discovery and clinical development of new agents in this molecular class
    • …
    corecore