2,015 research outputs found

    Tools and technologies in mathematical didactics

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    This short paper provides an overview of recent European research about the use and impact of tools and technologies in mathematical didactics. Such research is categorised as focusing on theoretical ideas, on algebraic knowledge when using spreadsheet and computer algebra (CAS), and on dynamic geometry software (DGS). The paper reveals the variety of software technologies, education levels, and methodologies utitised in European research

    Antimicrobial resistance in equine faecal Escherichia coli isolates from North West England

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    <p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>isolates of equine faecal origin were investigated for antibiotic resistance, resistance genes and their ability to perform horizontal transfer.</p> <p>Methods</p> <p>In total, 264 faecal samples were collected from 138 horses in hospital and community livery premises in northwest England, yielding 296 resistant <it>E. coli </it>isolates. Isolates were tested for susceptibility to antimicrobial drugs by disc diffusion and agar dilution methods in order to determine minimum inhibitory concentrations (MIC). PCR amplification was used to detect genes conferring resistance to: ampicillin (TEM and SHV beta-lactamase), chloramphenicol (<it>catI, catII, catIII </it>and <it>cml</it>), tetracycline <it>(tetA, tetB, tetC, tetD, tet E </it>and <it>tetG</it>), and trimethoprim (<it>dfrA1, dfrA9, dfrA12, dfrA13, dfr7</it>, and <it>dfr17</it>).</p> <p>Results</p> <p>The proportion of antibiotic resistant isolates, and multidrug resistant isolates (MDR) was significantly higher in hospital samples compared to livery samples (MDR: 48% of hospital isolates; 12% of livery isolates, p < 0.001). Resistance to ciprofloxacin and florfenicol were identified mostly within the MDR phenotypes. Resistance genes included <it>dfr</it>, TEM beta-lactamase, <it>tet </it>and <it>cat</it>, conferring resistance to trimethoprim, ampicillin, tetracycline and chloramphenicol, respectively. Within each antimicrobial resistance group, these genes occurred at frequencies of 93% (260/279), 91%, 86.8% and 73.5%, respectively; with 115/296 (38.8%) found to be MDR isolates. Conjugation experiments were performed on selected isolates and MDR phenotypes were readily transferred.</p> <p>Conclusions</p> <p>Our findings demonstrate that <it>E. coli </it>of equine faecal origin are commonly resistant to antibiotics used in human and veterinary medicine. Furthermore, our results suggest that most antibiotic resistance observed in equine <it>E. coli </it>is encoded by well-known and well-characterized resistant genes common to <it>E. coli </it>from man and domestic animals. These data support the ongoing concern about antimicrobial resistance, MDR, antimicrobial use in veterinary medicine and the zoonotic risk that horses could potentially pose to public health.</p

    The rationale for Janus kinase inhibitors for the treatment of spondyloarthritis

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    The pathogenesis of SpA is multifactorial and involves a range of immune cell types and cytokines, many of which utilize Janus kinase (JAK) pathways for signaling. In this review, we summarize the animal and pre-clinical data that have demonstrated the effects of JAK blockade on the underlying molecular mechanisms of SpA and provide a rationale for JAK inhibition for the treatment of SpA. We also review the available clinical trial data evaluating JAK inhibitors tofacitinib, baricitinib, peficitinib, filgotinib and upadacitinib in PsA, AS and related inflammatory diseases, which have demonstrated the efficacy of these agents across a range of SpA-associated disease manifestations. The available clinical trial data, supported by pre-clinical animal model studies demonstrate that JAK inhibition is a promising therapeutic strategy for the treatment of SpA and may offer the potential for improvements in multiple articular and extra-articular disease manifestations of PsA and AS

    Human PrimPol is a highly error-prone polymerase regulated by single-stranded DNA binding proteins

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    PrimPol is a recently identified polymerase involved in eukaryotic DNA damage tolerance, employed in both re-priming and translesion synthesis mechanisms to bypass nuclear and mitochondrial DNA lesions. In this report, we investigate how the enzymatic activities of human PrimPol are regulated. We show that, unlike other TLS polymerases, PrimPol is not stimulated by PCNA and does not interact with it in vivo. We identify that PrimPol interacts with both of the major single-strand binding proteins, RPA and mtSSB in vivo. Using NMR spectroscopy, we characterize the domains responsible for the PrimPol-RPA interaction, revealing that PrimPol binds directly to the N-terminal domain of RPA70. In contrast to the established role of SSBs in stimulating replicative polymerases, we find that SSBs significantly limit the primase and polymerase activities of PrimPol. To identify the requirement for this regulation, we employed two forward mutation assays to characterize PrimPol's replication fidelity. We find that PrimPol is a mutagenic polymerase, with a unique error specificity that is highly biased towards insertion-deletion errors. Given the error-prone disposition of PrimPol, we propose a mechanism whereby SSBs greatly restrict the contribution of this enzyme to DNA replication at stalled forks, thus reducing the mutagenic potential of PrimPol during genome replication

    MIRC-X: a highly-sensitive six telescope interferometric imager at the CHARA Array

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    MIRC-X (Michigan InfraRed Combiner-eXeter) is a new highly-sensitive six-telescope interferometric imager installed at the CHARA Array that provides an angular resolution equivalent of up to a 330 m diameter baseline telescope in J and H band wavelengths (λ2B∼0.6\tfrac{\lambda}{2B}\sim0.6 milli-arcseconds). We upgraded the original MIRC (Michigan InfraRed Combiner) instrument to improve sensitivity and wavelength coverage in two phases. First, a revolutionary sub-electron noise and fast-frame rate C-RED ONE camera based on a SAPHIRA detector was installed. Second, a new-generation beam combiner was designed and commissioned to (i) maximize sensitivity, (ii) extend the wavelength coverage to J-band, and (iii) enable polarization observations. A low-latency and fast-frame rate control software enables high-efficiency observations and fringe tracking for the forthcoming instruments at CHARA Array. Since mid-2017, MIRC-X has been offered to the community and has demonstrated best-case H-band sensitivity down to 8.2 correlated magnitude. MIRC-X uses single-mode fibers to coherently combine light of six telescopes simultaneously with an image-plane combination scheme and delivers a visibility precision better than 1%, and closure phase precision better than 1∘1^\circ. MIRC-X aims at (i) imaging protoplanetary disks, (ii) detecting exoplanets with precise astrometry, and (iii) imaging stellar surfaces and star-spots at an unprecedented angular resolution in the near-infrared. In this paper, we present the instrument design, installation, operation, and on-sky results, and demonstrate the imaging and astrometric capability of MIRC-X on the binary system ι\iota Peg. The purpose of this paper is to provide a solid reference for studies based on MIRC-X data and to inspire future instruments in optical interferometry.Comment: 31 pages, 29 figures, accepted for publication in The Astronomical Journa

    Methicillin-resistant Staphylococci in Companion Animals

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    We determined the molecular characteristics of methicillin-resistant staphylococci from animals and staff at a small animal and equine hospital. Methicillin-resistant Staphylococcus aureus (MRSA) identical to human EMRSA-15 was found in dogs and hospital staff. In contrast, 5 distinct MRSA strains were isolated from horses but not from hospital staff
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