79 research outputs found

    HerMES: The Contribution to the Cosmic Infrared Background from Galaxies Selected by Mass and Redshift

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    We quantify the fraction of the cosmic infrared background (CIB) that originates from galaxies identified in the UV/optical/near-infrared by stacking 81,250 (~35.7 arcmin^(–2)) K-selected sources (K_(AB) 350 μm. The contribution from galaxies in the log(M/M_☉) = 9.0-9.5 (lowest) and log(M/M_☉) = 11.0-12.0 (highest) stellar-mass bins contribute the least—both of order 5%—although the highest stellar-mass bin is a significant contributor to the luminosity density at z ≳ 2. The luminosities of the galaxies responsible for the CIB shifts from combinations of "normal" and luminous infrared galaxies (LIRGs) at λ ≾ 160 μm, to LIRGs at 160 ≾ λ ≾ 500 μm, to finally LIRGs and ultra-luminous infrared galaxies at λ ≳ 500 μm. Stacking analyses were performed using SIMSTACK, a novel algorithm designed to account for possible biases in the stacked flux density due to clustering. It is made available to the public at www.astro.caltech.edu/~viero/viero_homepage/toolbox.html

    Variation in pre-PCR processing of FFPE samples leads to discrepancies in BRAF and EGFR mutation detection: a diagnostic RING trial.

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    Aims Mutation detection accuracy has been described extensively; however, it is surprising that pre-PCR processing of formalin-fixed paraffin-embedded (FFPE) samples has not been systematically assessed in clinical context. We designed a RING trial to (i) investigate pre-PCR variability, (ii) correlate pre-PCR variation with EGFR/BRAF mutation testing accuracy and (iii) investigate causes for observed variation. Methods 13 molecular pathology laboratories were recruited. 104 blinded FFPE curls including engineered FFPE curls, cell-negative FFPE curls and control FFPE tissue samples were distributed to participants for pre-PCR processing and mutation detection. Follow-up analysis was performed to assess sample purity, DNA integrity and DNA quantitation. Results Rate of mutation detection failure was 11.9%. Of these failures, 80% were attributed to pre-PCR error. Significant differences in DNA yields across all samples were seen using analysis of variance (p<0.0001), and yield variation from engineered samples was not significant (p=0.3782). Two laboratories failed DNA extraction from samples that may be attributed to operator error. DNA extraction protocols themselves were not found to contribute significant variation. 10/13 labs reported yields averaging 235.8ng (95% CI 90.7 to 380.9) from cell-negative samples, which was attributed to issues with spectrophotometry. DNA measurements using Qubit Fluorometry demonstrated a median fivefold overestimation of DNA quantity by Nanodrop Spectrophotometry. DNA integrity and PCR inhibition were factors not found to contribute significant variation. Conclusions In this study, we provide evidence demonstrating that variation in pre-PCR steps is prevalent and may detrimentally affect the patient's ability to receive critical therapy. We provide recommendations for preanalytical workflow optimisation that may reduce errors in down-stream sequencing and for next-generation sequencing library generation

    Computational Analysis of Thermal Adaptation in Extremophilic Chitinases: The Achilles' Heel in Protein Structure and Industrial Utilization.

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    peer reviewedUnderstanding protein stability is critical for the application of enzymes in biotechnological processes. The structural basis for the stability of thermally adapted chitinases has not yet been examined. In this study, the amino acid sequences and X-ray structures of psychrophilic, mesophilic, and hyperthermophilic chitinases were analyzed using computational and molecular dynamics (MD) simulation methods. From the findings, the key features associated with higher stability in mesophilic and thermophilic chitinases were fewer and/or shorter loops, oligomerization, and less flexible surface regions. No consistent trends were observed between stability and amino acid composition, structural features, or electrostatic interactions. Instead, unique elements affecting stability were identified in different chitinases. Notably, hyperthermostable chitinase had a much shorter surface loop compared to psychrophilic and mesophilic homologs, implying that the extended floppy surface region in cold-adapted and mesophilic chitinases may have acted as a "weak link" from where unfolding was initiated. MD simulations confirmed that the prevalence and flexibility of the loops adjacent to the active site were greater in low-temperature-adapted chitinases and may have led to the occlusion of the active site at higher temperatures compared to their thermostable homologs. Following this, loop "hot spots" for stabilizing and destabilizing mutations were also identified. This information is not only useful for the elucidation of the structure-stability relationship, but will be crucial for designing and engineering chitinases to have enhanced thermoactivity and to withstand harsh industrial processing conditions

    Recommending video content for use in group-based reminiscence therapy

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    REMPAD is a semi-automated cloud-based system used to facilitate digital reminiscence therapy for patients with mild-to-moderate dementia, enacted in a group setting. REMPAD uses profiles for participants and groups to proactively recommend interactive video content from the Internet to match these profiles. In this chapter, we focus on the design of the system and then the system architecture, the system build, data curation, and usage scenarios. We also report a series of steps carried out as part of our user-centered design approach to system development, and a series of analyses on interaction logs which indicate various levels of effectiveness for different configurations of the recommendation algorithm we use. The results indicate high user satisfaction when using the system, and strong tendency towards repeated use in future

    A Comprehensive Phylogenetic Analysis of the Scleractinia (Cnidaria, Anthozoa) Based on Mitochondrial CO1 Sequence Data

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    Classical morphological taxonomy places the approximately 1400 recognized species of Scleractinia (hard corals) into 27 families, but many aspects of coral evolution remain unclear despite the application of molecular phylogenetic methods. In part, this may be a consequence of such studies focusing on the reef-building (shallow water and zooxanthellate) Scleractinia, and largely ignoring the large number of deep-sea species. To better understand broad patterns of coral evolution, we generated molecular data for a broad and representative range of deep sea scleractinians collected off New Caledonia and Australia during the last decade, and conducted the most comprehensive molecular phylogenetic analysis to date of the order Scleractinia.Partial (595 bp) sequences of the mitochondrial cytochrome oxidase subunit 1 (CO1) gene were determined for 65 deep-sea (azooxanthellate) scleractinians and 11 shallow-water species. These new data were aligned with 158 published sequences, generating a 234 taxon dataset representing 25 of the 27 currently recognized scleractinian families.There was a striking discrepancy between the taxonomic validity of coral families consisting predominantly of deep-sea or shallow-water species. Most families composed predominantly of deep-sea azooxanthellate species were monophyletic in both maximum likelihood and Bayesian analyses but, by contrast (and consistent with previous studies), most families composed predominantly of shallow-water zooxanthellate taxa were polyphyletic, although Acroporidae, Poritidae, Pocilloporidae, and Fungiidae were exceptions to this general pattern. One factor contributing to this inconsistency may be the greater environmental stability of deep-sea environments, effectively removing taxonomic "noise" contributed by phenotypic plasticity. Our phylogenetic analyses imply that the most basal extant scleractinians are azooxanthellate solitary corals from deep-water, their divergence predating that of the robust and complex corals. Deep-sea corals are likely to be critical to understanding anthozoan evolution and the origins of the Scleractinia

    An intrinsically disordered proteins community for ELIXIR.

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    Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) are now recognised as major determinants in cellular regulation. This white paper presents a roadmap for future e-infrastructure developments in the field of IDP research within the ELIXIR framework. The goal of these developments is to drive the creation of high-quality tools and resources to support the identification, analysis and functional characterisation of IDPs. The roadmap is the result of a workshop titled "An intrinsically disordered protein user community proposal for ELIXIR" held at the University of Padua. The workshop, and further consultation with the members of the wider IDP community, identified the key priority areas for the roadmap including the development of standards for data annotation, storage and dissemination; integration of IDP data into the ELIXIR Core Data Resources; and the creation of benchmarking criteria for IDP-related software. Here, we discuss these areas of priority, how they can be implemented in cooperation with the ELIXIR platforms, and their connections to existing ELIXIR Communities and international consortia. The article provides a preliminary blueprint for an IDP Community in ELIXIR and is an appeal to identify and involve new stakeholders

    Evaluating Enzymatic Productivity&mdash;The Missing Link to Enzyme Utility

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    Kinetic productivity analysis is critical to the characterization of enzyme catalytic performance and capacity. However, productivity analysis has been largely overlooked in the published literature. Less than 0.01% of studies which report on enzyme characterization present productivity analysis, despite the fact that this is the only measurement method that provides a reliable indicator of potential commercial utility. Here, we argue that reporting productivity data involving native, modified, and immobilized enzymes under different reaction conditions will be of immense value in optimizing enzymatic processes, with a view to accelerating biotechnological applications. With the use of examples from wide-ranging studies, we demonstrate that productivity is a measure of critical importance to the translational and commercial use of enzymes and processes that employ them. We conclude the review by suggesting steps to maximize the productivity of enzyme catalyzed reactions

    Characterisation of Bacteriophage vB_SmaM_Ps15 Infective to <i>Stenotrophomonas maltophilia</i> Clinical Ocular Isolates

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    Recent acknowledgment that multidrug resistant Stenotrophomonas maltophilia strains can cause severe infections has led to increasing global interest in addressing its pathogenicity. While being primarily associated with hospital-acquired respiratory tract infections, this bacterial species is also relevant to ophthalmology, particularly to contact lens-related diseases. In the current study, the capacity of Stenotrophomonas phage vB_SmaM_Ps15 to infect ocular S. maltophilia strains was investigated to explore its future potential as a phage therapeutic. The phage proved to be lytic to a range of clinical isolates collected in Australia from eye swabs, contact lenses and contact lens cases that had previously shown to be resistant to several antibiotics and multipurpose contact lenses disinfectant solutions. Morphological analysis by transmission electron microscopy placed the phage into the Myoviridae family. Its genome size was 161,350 bp with a G + C content of 54.2%, containing 276 putative protein-encoding genes and 24 tRNAs. A detailed comparative genomic analysis positioned vB_SmaM_Ps15 as a new species of the Menderavirus genus, which currently contains six very similar globally distributed members. It was confirmed as a virulent phage, free of known lysogenic and pathogenicity determinants, which supports its potential use for the treatment of S. maltophilia eye infections
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