1,105 research outputs found

    Using Insights from Psychology and Language to Improve How People Reason with Description Logics

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    Inspired by insights from theories of human reasoning and language, we propose additions to the Manchester OWL Syntax to improve comprehensibility. These additions cover: functional and inverse functional properties, negated conjunction, the definition of exceptions, and existential and universal restrictions. By means of an empirical study, we demonstrate the effectiveness of a number of these additions, in particular: the use of solely to clarify the uniqueness of the object in a functional property; the replacement of and with intersection in conjunction, which was particularly beneficial in negated conjunction; the use of except as a substitute for and not; and the replacement of some with including and only with noneOrOnly, which helped in certain situations to clarify the nature of these restrictions

    Redevelopment of the Predict: Breast Cancer website and recommendations for developing interfaces to support decision-making.

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    OBJECTIVES: To develop a new interface for the widely used prognostic breast cancer tool: Predict: Breast Cancer. To facilitate decision-making around post-surgery breast cancer treatments. To derive recommendations for communicating the outputs of prognostic models to patients and their clinicians. METHOD: We employed a user-centred design process comprised of background research and iterative testing of prototypes with clinicians and patients. Methods included surveys, focus groups and usability testing. RESULTS: The updated interface now caters to the needs of a wider audience through the addition of new visualisations, instantaneous updating of results, enhanced explanatory information and the addition of new predictors and outputs. A programme of future research was identified and is now underway, including the provision of quantitative data on the adverse effects of adjuvant breast cancer treatments. Based on our user-centred design process, we identify six recommendations for communicating the outputs of prognostic models including the need to contextualise statistics, identify and address gaps in knowledge, and the critical importance of engaging with prospective users when designing communications. CONCLUSIONS: For prognostic algorithms to fulfil their potential to assist with decision-making they need carefully designed interfaces. User-centred design puts patients and clinicians needs at the forefront, allowing them to derive the maximum benefit from prognostic models

    RAD sequencing sheds new light on the genetic structure and local adaptation of European scallops and resolves their demographic histories.

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    Recent developments in genomics are advancing our understanding of the processes shaping population structure in wild organisms. In particular, reduced representation sequencing has facilitated the generation of dense genetic marker datasets that provide greater power for resolving population structure, investigating the role of selection and reconstructing demographic histories. We therefore used RAD sequencing to study the great scallop Pecten maximus and its sister species P. jacobeus along a latitudinal cline in Europe. Analysis of 219 samples genotyped at 82,439 single nucleotide polymorphisms clearly resolved an Atlantic and a Norwegian group within P. maximus as well as P. jacobeus, in support of previous studies. Fine-scale structure was also detected, including pronounced differences involving Mulroy Bay in Ireland, where scallops are commercially cultured. Furthermore, we identified a suite of 279 environmentally associated loci that resolved a contrasting phylogenetic pattern to the remaining neutral loci, consistent with ecologically mediated divergence. Finally, demographic inference provided support for the two P. maximus groups having diverged during the last glacial maximum and subsequently expanded, whereas P. jacobeus diverged around 95,000 generations ago and experienced less pronounced expansion. Our results provide an integrative perspective on the factors shaping genome-wide differentiation in a commercially important marine invertebrate

    Greasing the wheels or a spanner in the works?:Regulation of the cardiac sodium pump by palmitoylation

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    The ubiquitous sodium/potassium ATPase (Na pump) is the most abundant primary active transporter at the cell surface of multiple cell types, including ventricular myocytes in the heart. The activity of the Na pump establishes transmembrane ion gradients that control numerous events at the cell surface, positioning it as a key regulator of the contractile and metabolic state of the myocardium. Defects in Na pump activity and regulation elevate intracellular Na in cardiac muscle, playing a causal role in the development of cardiac hypertrophy, diastolic dysfunction, arrhythmias and heart failure. Palmitoylation is the reversible conjugation of the fatty acid palmitate to specific protein cysteine residues; all subunits of the cardiac Na pump are palmitoylated. Palmitoylation of the pump’s accessory subunit phospholemman (PLM) by the cell surface palmitoyl acyl transferase DHHC5 leads to pump inhibition, possibly by altering the relationship between the pump catalytic α subunit and specifically bound membrane lipids. In this review, we discuss the functional impact of PLM palmitoylation on the cardiac Na pump and the molecular basis of recognition of PLM by its palmitoylating enzyme DHHC5, as well as effects of palmitoylation on Na pump cell surface abundance in the cardiac muscle. We also highlight the numerous unanswered questions regarding the cellular control of this fundamentally important regulatory process

    Restrictive ID policies: implications for health equity

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    We wish to thank Synod Community Services for their critical work to develop, support, and implement a local government-issued ID in Washtenaw County, MI. We also thank Yousef Rabhi of the Michigan House of Representatives and Janelle Fa'aola of the Washtenaw ID Task Force, Lawrence Kestenbaum of the Washtenaw County Clerk's Office, Sherriff Jerry Clayton of the Washtenaw County Sherriff's Office, and the Washtenaw ID Task Force for their tireless commitment to developing and supporting the successful implementation of the Washtenaw ID. Additionally, we thank Vicenta Vargas and Skye Hillier for their contributions to the Washtenaw ID evaluation. We thank the Curtis Center for Research and Evaluation at the University of Michigan School of Social Work, the National Center for Institutional Diversity at the University of Michigan, and the University of California-Irvine Department of Chicano/Latino Studies and Program in Public Health for their support of the Washtenaw ID community-academic research partnership. Finally, we thank the reviewers for their helpful comments on earlier drafts of this manuscript. (Curtis Center for Research and Evaluation at the University of Michigan School of Social Work; National Center for Institutional Diversity at the University of Michigan; University of California-Irvine Department of Chicano/Latino Studies; Program in Public Health)https://link.springer.com/content/pdf/10.1007/s10903-017-0579-3.pdfPublished versio

    Psychometric analysis of the scale for the predisposition to the occurrence of adverse events in nursing care provided in ICUS

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    OBJECTIVE: to present the result of the validity and reliability studies concerning the Scale for the Predisposition to the Occurrence of Adverse Events (EPEA). METHOD: construct validity was based on Principal Components Analysis. RESULTS: reliability verified through Cronbach's alpha indicated good reliability (structure α=0.80; process α=0.92). CONCLUSION: based on its psychometric indicators, the EPEA can be considered a valid measure to assess the attitudes of nurses in relation to factors that potentially lead to the occurrence of adverse events in ICUs

    Assessing the Contribution of Heme-Iron Acquisition to Staphylococcus aureus Pneumonia Using Computed Tomography

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    S. aureus acquires heme-iron using the iron regulated surface determinant (Isd) system and the heme transport system (Hts) with both systems showing critical importance in systemic models of infection. The contribution of heme-iron acquisition to staphylococcal pneumonia has not yet been elucidated. In addition, the use of computed tomography (CT) for the evaluation of staphylococcal pneumonia and its correlation to pathologic examination of infected lung tissue has not been performed to date. We have applied CT-based imaging to a murine model of staphylococcal pneumonia to determine the virulence contribution of heme-iron acquisition through the Hts and Isd systems.Mice were intranasally inoculated with approximately 1.0 x 10(8) colony forming units (CFU) of S. aureus. Lungs from mice infected with wild type S. aureus or strains deficient in isdB and isdH (DeltaisdBH) or htsA and isdE (DeltahtsADeltaisdE) were harvested at 24 hours. Histology, radiographic appearance by computed tomography (CT), percent mortality and bacterial burden were evaluated. Infection with S. aureus DeltaisdBH and DeltahtsADeltaisdE did not result in a statistically significant difference in mortality or bacterial burden as compared to controls. CT imaging of infected mice also did not reveal an appreciable difference between the various strains when compared to wild type, but did correlate with pathologic findings of pneumonia. However, a systemic model of infection using the DeltahtsADeltaisdE strain revealed a statistically significant decrease in bacterial burden in the lung, heart and kidneys.The development of staphylococcal pneumonia in this murine model is not dependent on hemoglobin binding or heme-iron uptake into S. aureus. However, this model does reveal that heme-iron acquisition contributes to the pathogenesis of systemic staphylococcal infections. In addition, CT imaging of murine lungs is an attractive adjunct to histologic analysis for the confirmation and staging of pneumonia

    Calcitization of aragonitic bryozoans in Cenozoic tropical carbonates from East Kalimantan, Indonesia

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    © The Author(s) 2016. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The file attached is the published version of the article

    The C-Terminal Domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC Is a Lectin-Like Carbohydrate Binding Module

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    The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Herein, we present the crystal structure of the C-terminal hydrophilic domain of the ethambutol-sensitive Araf transferase M. tuberculosis EmbC, which is essential for LAM synthesis. The structure of the C-terminal domain of EmbC (EmbCCT) encompasses two sub-domains of different folds, of which subdomain II shows distinct similarity to lectin-like carbohydrate-binding modules (CBM). Co-crystallisation with a cell wall-derived di-arabinoside acceptor analogue and structural comparison with ligand-bound CBMs suggest that EmbCCT contains two separate carbohydrate binding sites, associated with subdomains I and II, respectively. Single-residue substitution of conserved tryptophan residues (Trp868, Trp985) at these respective sites inhibited EmbC-catalysed extension of LAM. The same substitutions differentially abrogated binding of di- and penta-arabinofuranoside acceptor analogues to EmbCCT, linking the loss of activity to compromised acceptor substrate binding, indicating the presence of two separate carbohydrate binding sites, and demonstrating that subdomain II indeed functions as a carbohydrate-binding module. This work provides the first step towards unravelling the structure and function of a GT-C-type glycosyltransferase that is essential in M. tuberculosis. Author Summary Top Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis, burdens large swaths of the world population. Treatment of active TB typically requires administration of an antibiotic cocktail over several months that includes the drug ethambutol. This front line compound inhibits a set of arabinosyltransferase enzymes, called EmbA, EmbB and EmbC, which are critical for the synthesis of arabinan, a vital polysaccharide in the pathogen's unique cell envelope. How precisely ethambutol inhibits arabinosyltransferase activity is not clear, in part because structural information of its pharmacological targets has been elusive. Here, we report the high-resolution structure of the C-terminal domain of the ethambutol-target EmbC, a 390-amino acid fragment responsible for acceptor substrate recognition. Combining the X-ray crystallographic analysis with structural comparisons, site-directed mutagenesis, activity and ligand binding assays, we identified two regions in the C-terminal domain of EmbC that are capable of binding acceptor substrate mimics and are critical for activity of the full-length enzyme. Our results begin to define structure-function relationships in a family of structurally uncharacterised membrane-embedded glycosyltransferases, which are an important target for tuberculosis therapy
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