2,151 research outputs found

    Saccharomyces cerevisiae and Schizosaccharomyces pombe contain a homologue to the 54-kD subunit of the signal recognition particle that in S. cerevisiae is essential for growth.

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    We have isolated and sequenced genes from Saccharomyces cerevisiae (SRP54SC) and Schizosaccharomyces pombe (SRP54sp) encoding proteins homologous to both the 54-kD protein subunit (SRP54mam) of the mammalian signal recognition particle (SRP) and the product of a gene of unknown function in Escherichia coli, ffh (Römisch, K., J. Webb, J. Herz, S. Prehn, R. Frank, M. Vingron, and B. Dobberstein. 1989. Nature (Lond.). 340:478-482; Bernstein H. D., M. A. Poritz, K. Strub, P. J. Hoben, S. Brenner, P. Walter. 1989. Nature (Lond.). 340:482-486). To accomplish this we took advantage of short stretches of conserved sequence between ffh and SRP54mam and used the polymerase chain reaction (PCR) to amplify fragments of the homologous yeast genes. The DNA sequences predict proteins for SRP54sc and SRP54sp that are 47% and 52% identical to SRP54mam, respectively. Like SRP54mam and ffh, both predicted yeast proteins contain a GTP binding consensus sequence in their NH2-terminal half (G-domain), and methionine-rich sequences in their COOH-terminal half (M-domain). In contrast to SRP54mam and ffh the yeast proteins contain additional Met-rich sequences inserted at the COOH-terminal portion of the M-domain. SRP54sp contains a 480-nucleotide intron located 78 nucleotides from the 5' end of the open reading frame. Although the function of the yeast homologues is unknown, gene disruption experiments in S. cerevisiae show that the gene is essential for growth. The identification of SRP54sc and SRP54sp provides the first evidence for SRP related proteins in yeast

    Custodians of contemporary pluralism? Acas' evolving role in addressing conflict during a time of economic and regulatory flux

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    AbstractThis paper charts the development of Acas over the last two decades as it responds to the changing context of British employment relations. While dispute resolution services have evolved to focus on individual disputes, Acas has remained true to its pluralist roots through its training and advisory services that continue to promote ‘good employment relations’

    The Value of Online Information Privacy: An Empirical Investigation

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    Concern over online information privacy is widespread and rising. However, prior research is silent about the value of information privacy in the presence of potential benefits from sharing personally identifiable information. Analyzing individuals' trade-offs between the benefits and costs of providing personal information to websites revealed that benefits, monetary reward and future convenience, significantly affect individuals' preferences over websites with differing privacy policies. Quantifying the value of website privacy protection revealed that among U.S. subjects, protection against errors, improper access, and secondary use of personal information is worth US $30.49 - 44.62. Finally, three distinct segments of Internet consumers were determined: privacy guardians, information sellers and convenience seekers.

    The HSV-1 Latency-Associated Transcript Functions to Repress Latent Phase Lytic Gene Expression and Suppress Virus Reactivation from Latently Infected Neurons

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    open access articleHerpes simplex virus 1 (HSV-1) establishes life-long latent infection within sensory neurons, during which viral lytic gene expression is silenced. The only highly expressed viral gene product during latent infection is the latency-associated transcript (LAT), a non-protein coding RNA that has been strongly implicated in the epigenetic regulation of HSV-1 gene expression. We have investigated LAT-mediated control of latent gene expression using chromatin immunoprecipitation analyses and LAT-negative viruses engineered to express firefly luciferase or β-galactosidase from a heterologous lytic promoter. Whilst we were unable to determine a significant effect of LAT expression upon heterochromatin enrichment on latent HSV-1 genomes, we show that reporter gene expression from latent HSV-1 genomes occurs at a greater frequency in the absence of LAT. Furthermore, using luciferase reporter viruses we have observed that HSV-1 gene expression decreases during long-term latent infection, with a most marked effect during LAT-negative virus infection. Finally, using a fluorescent mouse model of infection to isolate and culture single latently infected neurons, we also show that reactivation occurs at a greater frequency from cultures harbouring LAT-negative HSV-1. Together, our data suggest that the HSV-1 LAT RNA represses HSV-1 gene expression in small populations of neurons within the mouse TG, a phenomenon that directly impacts upon the frequency of reactivation and the maintenance of the transcriptionally active latent reservoir

    Time-Splitting Coupling of WaveDyn with OpenFOAM by Fidelity Limit Identified from a WEC in Extreme Waves

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    Survivability assessment is the complexity compromising Wave energy development. The present study develops a hybrid model aiming to reduce computational power while maintaining accuracy for survivability assessment of a Point-Absorber (PA) Wave Energy Converter (WEC) in extreme Wave Structure Interaction (WSI). This method couples the fast inviscid linear potential flow time-domain model WaveDyn (1.2, DNV-GL, Bristol, UK) with the fully nonlinear viscous Navier–Stokes Computational Fluid Dynamics (CFD) code OpenFOAM (4.2, OpenFOAM.org, London, UK). The coupling technique enables the simulation to change between codes, depending on an indicator relating to wave steepness identified as a function of the confidence in the linear model solution. During the CFD part of the simulation, the OpenFOAM solution is returned to WaveDyn via an additional load term, thus including viscous effects. Developments ensure a satisfactory initialisation of CFD simulation to be achieved from a ‘hot-start’ time, where the wave-field is developed and the device is in motion. The coupled model successfully overcomes identified inaccuracies in the WaveDyn code due to the inviscid assumption and the high computational cost of the OpenFOAM code. Experimental data of a PA response under extreme deterministic events (NewWave) are used to assess WaveDyn’s validity limit as a function of wave steepness, in order to validate CFD code and develop the coupling. The hybrid code demonstrates the applicability of WaveDyn validity limit and shows promising results for long irregular sea-state applications

    Comparison of Identification Methods of a Time-varying Insulin Sensitivity Parameter in a Simulation Model of Glucose Metabolism in the Critically Ill

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    6-pages (invited)Models of glucose metabolism can help to simulate and predict the blood glucose response in hyperglycaemic, critically ill patients. Model prediction performance depends on a su ciently accurate estimation of the patient's time-varying insulin sensitivity. The work presents three least squares approaches, the integral method and a Bayesian method that have been compared by prediction accuracy on an absolute and on a relative scale. Clinical data yields 1491 blood glucose predictions based on 10 critically ill patients were processed. The Bayesian approach proved to be best with small errors (9:7% absolute percent error, 14:7 root mean square of logarithmic error for prediction times 2h), and fewer and smaller outliers compared to the other methods. Computationally, the Bayesian method took 1.5 times longer per prediction compared to the fastest method. It can be concluded that a Bayesian parameter estimation gives safe and e ective results for the insulin sensitivity estimation for this model

    The Patient Assessment of Chronic Illness Care produces measurements along a single dimension: results from a Mokken analysis.

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    BACKGROUND: As the worldwide prevalence of chronic illness increases so too does the demand for novel treatments to improve chronic illness care. Quantifying improvement in chronic illness care from the patient perspective relies on the use of validated patient-reported outcome measures. In this analysis we examine the psychometric and scaling properties of the Patient Assessment of Chronic Illness Care (PACIC) questionnaire for use in the United Kingdom by applying scale data to the non-parametric Mokken double monotonicity model. METHODS: Data from 1849 patients with long-term conditions in the UK who completed the 20-item PACIC were analysed using Mokken analysis. A three-stage analysis examined the questionnaire's scalability, monotonicity and item ordering. An automated item selection procedure was used to assess the factor structure of the scale. Analysis was conducted in an 'evaluation' dataset (n = 956) and results were confirmed using an independent 'validation' (n = 890) dataset. RESULTS: Automated item selection procedures suggested that the 20 items represented a single underlying trait representing "patient assessment of chronic illness care": this contrasts with the multiple domains originally proposed. Six items violated invariant item ordering and were removed. The final 13-item scale had no further issues in either the evaluation or validation samples, including excellent scalability (Ho = .50) and reliability (Rho = .88). CONCLUSIONS: Following some modification, the 13-items of the PACIC were successfully fitted to the non-parametric Mokken model. These items have psychometrically robust and produce a single ordinal summary score. This score will be useful for clinicians or researchers to assess the quality of chronic illness care from the patient's perspective
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