169 research outputs found

    Beliefs about Social Distancing During COVID-19 Stay-At-Home Orders: A Theory-Based Salient Belief Elicitation

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    Understanding the beliefs about social distancing behaviors is required to inform 2019 coronavirus disease (COVID-19) interventions that are based on theory, research, and evidence. This study investigated the salient beliefs related to social distancing. United States adults (n = 106) recruited from Amazon’s Mechanical Turk completed an online reasoned action approach belief elicitation from April 19 to April 25, 2020. Behavioral beliefs (advantages and disadvantages), normative beliefs (approvers and disapprovers), and control beliefs (facilitators and barriers) related to social distancing were elicited via open-ended questions. A content analysis was performed, and kappa statistics revealed high levels of interrater reliability (α = 0.86-0.96). Results revealed that a perceived salient advantage to social distancing was individual COVID-19 prevention, more so than community prevention. The most cited disadvantage was that social distancing could prevent participants from socially interacting with others, which could negatively impact mental health. Family and friends were the most mentioned approvers, while people who hold conservative ideologies and negative attitudes about COVID-19 were the most frequent disapprovers. Supply accessibility and store policies were the most listed facilitators. Results suggest three implications. First, pandemic-related public health and social marketing campaigns should focus more on individual health benefits than community health benefits. Second, digital public health interventions that address social connectedness and mental health outcomes are critical during pandemics. Third, public health scientists and practitioners should work with local and national media outlets and political leaders to create community-tailored and evidence-based information to increase adherence of mitigation strategies

    Computing exponentially faster: Implementing a nondeterministic universal Turing machine using DNA

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    The theory of computer science is based around Universal Turing Machines (UTMs): abstract machines able to execute all possible algorithms. Modern digital computers are physical embodiments of UTMs. The nondeterministic polynomial (NP) time complexity class of problems is the most significant in computer science, and an efficient (i.e. polynomial P) way to solve such problems would be of profound economic and social importance. By definition nondeterministic UTMs (NUTMs) solve NP complete problems in P time. However, NUTMs have previously been believed to be physically impossible to construct. Thue string rewriting systems are computationally equivalent to UTMs, and are naturally nondeterministic. Here we describe the physical design for a NUTM that implements a universal Thue system. The design exploits the ability of DNA to replicate to execute an exponential number of computational paths in P time. Each Thue rewriting step is embodied in a DNA edit implemented using a novel combination of polymerase chain reactions and site-directed mutagenesis. We demonstrate that this design works using both computational modelling and in vitro molecular biology experimentation. The current design has limitations, such as restricted error-correction. However, it opens up the prospect of engineering NUTM based computers able to outperform all standard computers on important practical problems

    The influence of perfusion solution on renal graft viability assessment

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    BACKGROUND: Kidneys from donors after cardiac or circulatory death are exposed to extended periods of both warm ischemia and intra-arterial cooling before organ recovery. Marshall’s hypertonic citrate (HOC) and Bretschneider’s histidine-tryptophan-ketoglutarate (HTK) preservation solutions are cheap, low viscosity preservation solutions used clinically for organ flushing. The aim of the present study was to evaluate the effects of these two solutions both on parameters used in clinical practice to assess organ viability prior to transplantation and histological evidence of ischemic injury after reperfusion. METHODS: Rodent kidneys were exposed to post-mortem warm ischemia, extended intra-arterial cooling (IAC) (up to 2 h) with preservation solution and reperfusion with either Krebs-Hensleit or whole blood in a transplant model. Control kidneys were either reperfused directly after retrieval or stored in 0.9% saline. Biochemical, immunological and histological parameters were assessed using glutathione-S-transferase (GST) enzymatic assays, polymerase chain reaction and mitochondrial electron microscopy respectively. Vascular function was assessed by supplementing the Krebs-Hensleit perfusion solution with phenylephrine to stimulate smooth muscle contraction followed by acetylcholine to trigger endothelial dependent relaxation. RESULTS: When compared with kidneys reperfused directly post mortem, 2 h of IAC significantly reduced smooth muscle contractile function, endothelial function and upregulated vascular cellular adhesion molecule type 1 (VCAM-1) independent of the preservation solution. However, GST release, vascular resistance, weight gain and histological mitochondrial injury were dependent on the preservation solution used. CONCLUSIONS: We conclude that initial machine perfusion viability tests, including ischemic vascular resistance and GST, are dependent on the perfusion solution used during in situ cooling. HTK-perfused kidneys will be heavier, have higher GST readings and yet reduced mitochondrial ischemic injury when compared with HOC-perfused kidneys. Clinicians should be aware of this when deciding which kidneys to transplant or discard

    Sequential design of computer experiments for the estimation of a probability of failure

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    This paper deals with the problem of estimating the volume of the excursion set of a function f:RdRf:\mathbb{R}^d \to \mathbb{R} above a given threshold, under a probability measure on Rd\mathbb{R}^d that is assumed to be known. In the industrial world, this corresponds to the problem of estimating a probability of failure of a system. When only an expensive-to-simulate model of the system is available, the budget for simulations is usually severely limited and therefore classical Monte Carlo methods ought to be avoided. One of the main contributions of this article is to derive SUR (stepwise uncertainty reduction) strategies from a Bayesian-theoretic formulation of the problem of estimating a probability of failure. These sequential strategies use a Gaussian process model of ff and aim at performing evaluations of ff as efficiently as possible to infer the value of the probability of failure. We compare these strategies to other strategies also based on a Gaussian process model for estimating a probability of failure.Comment: This is an author-generated postprint version. The published version is available at http://www.springerlink.co

    The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

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    Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed

    Climate change implications for tidal marshes and food web linkages to estuarine and coastal nekton

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    Climate change is altering naturally fluctuating environmental conditions in coastal and estuarine ecosystems across the globe. Departures from long-term averages and ranges of environmental variables are increasingly being observed as directional changes [e.g., rising sea levels, sea surface temperatures (SST)] and less predictable periodic cycles (e.g., Atlantic or Pacific decadal oscillations) and extremes (e.g., coastal flooding, marine heatwaves). Quantifying the short- and long-term impacts of climate change on tidal marsh seascape structure and function for nekton is a critical step toward fisheries conservation and management. The multiple stressor framework provides a promising approach for advancing integrative, cross-disciplinary research on tidal marshes and food web dynamics. It can be used to quantify climate change effects on and interactions between coastal oceans (e.g., SST, ocean currents, waves) and watersheds (e.g., precipitation, river flows), tidal marsh geomorphology (e.g., vegetation structure, elevation capital, sedimentation), and estuarine and coastal nekton (e.g., species distributions, life history adaptations, predator-prey dynamics). However, disentangling the cumulative impacts of multiple interacting stressors on tidal marshes, whether the effects are additive, synergistic, or antagonistic, and the time scales at which they occur, poses a significant research challenge. This perspective highlights the key physical and ecological processes affecting tidal marshes, with an emphasis on the trophic linkages between marsh production and estuarine and coastal nekton, recommended for consideration in future climate change studies. Such studies are urgently needed to understand climate change effects on tidal marshes now and into the future
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