2,296 research outputs found

    Variability of Quasilinear Diffusion Coefficients for Plasmaspheric Hiss

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    In the outer radiation belt, the acceleration and loss of high‐energy electrons is largely controlled by wave‐particle interactions. Quasilinear diffusion coefficients are an efficient way to capture the small‐scale physics of wave‐particle interactions due to magnetospheric wave modes such as plasmaspheric hiss. The strength of quasilinear diffusion coefficients as a function of energy and pitch angle depends on both wave parameters and plasma parameters such as ambient magnetic field strength, plasma number density, and composition. For plasmaspheric hiss in the magnetosphere, observations indicate large variations in the wave intensity and wave normal angle, but less is known about the simultaneous variability of the magnetic field and number density. We use in situ measurements from the Van Allen Probe mission to demonstrate the variability of selected factors that control the size and shape of pitch angle diffusion coefficients: wave intensity, magnetic field strength, and electron number density. We then compare with the variability of diffusion coefficients calculated individually from colocated and simultaneous groups of measurements. We show that the distribution of the plasmaspheric hiss diffusion coefficients is highly non‐Gaussian with large variance and that the distributions themselves vary strongly across the three phase space bins studied. In most bins studied, the plasmaspheric hiss diffusion coefficients tend to increase with geomagnetic activity, but our results indicate that new approaches that include natural variability may yield improved parameterizations. We suggest methods like stochastic parameterization of wave‐particle interactions could use variability information to improve modeling of the outer radiation belt

    A tale of two studies: Study design and our understanding of SARS-CoV-2 seroprevalence

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    The COVID-19 pandemic is arguably the most important public health crisis of the last century. To date, infections with the SARS-CoV-2 virus have caused nearly 300,000 deaths in the United States alone [1], while also contributing to substantial excess morbidity and mortality from delayed and deferred care [2]. In addition to the direct and indirect health impacts, policies intended to limit the spread of the disease have resulted in large-scale disruptions to education systems, economic activity, and social networks. Put simply, the COVID-19 pandemic has impacted the daily lives of nearly all Americans in a way that no other health crisis has in our lifetimes

    A Review of Family-Based Tests for Linkage Disequilibrium between a Quantitative Trait and a Genetic Marker

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    Quantitative trait transmission/disequilibrium tests (quantitative TDTs) are commonly used in family-based genetic association studies of quantitative traits. Despite the availability of various quantitative TDTs, some users are not aware of the properties of these tests and the relationships between them. This review aims at outlining the broad features of the various quantitative TDT procedures carried out in the frequently used QTDT and FBAT packages. Specifically, we discuss the “Rabinowitz” and the “Monks-Kaplan” procedures, as well as the various “Abecasis” and “Allison” regression-based procedures. We focus on the models assumed in these tests and the relationships between them. Moreover, we discuss what hypotheses are tested by the various quantitative TDTs, what testing procedures are best suited to various forms of data, and whether the regression-based tests overcome population stratification problems. Finally, we comment on power considerations in the choice of the test to be used. We hope this brief review will shed light on the similarities and differences of the various quantitative TDTs

    Cytosine deaminase base editing to restore COL7A1 in dystrophic epidermolysis bullosa human:murine skin model

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    Recessive dystrophic epidermolysis bullosa (RDEB) is a debilitating blistering skin disorder caused by loss-of-function mutations in COL7A1 encoding type VII collagen (C7), the main component of anchoring fibrils (AFs) at the dermal-epidermal junction (DEJ). Although conventional gene therapy approaches through viral vectors have been tested in pre-clinical and clinical trials, they are limited by transgene size constraints and only support unregulated gene expression. Genome editing could potentially overcome some of these limitations, and CRISPR/Cas9 has already been applied in research studies to restore COL7A1 expression. Delivery of suitable repair templates for repair of DNA cleaved by Cas9 is still major challenge, and alternative base editing strategies may offer corrective solutions for certain mutations. We demonstrate highly targeted and efficient cytidine deamination and molecular correction of a defined RDEB mutation (c.425A>G) leading to restoration of full-length C7 protein expression in primary human fibroblasts and iPSCs. C7 basement membrane expression and skin architecture were restored with de novo AFs identified by electron microscopy in base edited human RDEB grafts recovered from immunodeficient mice. The results demonstrate the potential and promise of emerging base editing technologies in tackling inherited disorders with well-defined single nucleotide mutations

    The evolution o constitutive and induced defences to infectious disease

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    In response to infectious disease, hosts typically mount both constitutive and induced defences. Constitutive defence prevents infection in the first place, while induced defence typically shortens the infectious period. The two routes to defence, therefore, have very different implications not only to individuals but also to the epidemiology of the disease. Moreover, the costs of constitutive defences are likely to be paid even in the absence of disease, while induced defences are likely to incur the most substantial costs when they are used in response to infection. We examine theoretically the evolutionary implications of these fundamental differences. A key result is that high virulence in the parasite typically selects for higher induced defences even if they result in immunopathology leading to very high disease mortality. Disease impacts on fecundity are critical to the relative investment in constitutive and induced defence with important differences found when parasites castrate their hosts. The trade-off between constitutive and induced defence has been cited as a cause of the diversity in defence, but we show that the trade-off alone is unlikely to lead to diversity. Our models provide a framework to examine relative investment in different defence components both experimentally and in the field

    Are autistic traits measured equivalently in individuals with and without an Autism Spectrum Disorder?:An invariance analysis of the Autism Spectrum Quotient Short Form

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    It is common to administer measures of autistic traits to those without autism spectrum disorders (ASDs) with, for example, the aim of understanding autistic personality characteristics in non-autistic individuals. Little research has examined the extent to which measures of autistic traits actually measure the same traits in the same way across those with and without an ASD. We addressed this question using a multi-group confirmatory factor invariance analysis of the Autism Quotient Short Form (AQ-S: Hoekstra et al. in J Autism Dev Disord 41(5):589-596, 2011) across those with (n = 148) and without (n = 168) ASD. Metric variance (equality of factor loadings), but not scalar invariance (equality of thresholds), held suggesting that the AQ-S measures the same latent traits in both groups, but with a bias in the manner in which trait levels are estimated. We, therefore, argue that the AQ-S can be used to investigate possible causes and consequences of autistic traits in both groups separately, but caution is due when combining or comparing levels of autistic traits across the two group

    SWAMI: A SWARM-INTELLIGENT OPTIMIZATION TECHNIQUE FOR VOLTAGE COLLAPSE MITIGATION

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    In this paper, a voltage collapse optimization system based on comparative studies of swarm-intelligent techniques is proposed for voltage collapse mitigation in power system network. The approach draws inspiration from the idea of utilizing the intelligent behavior of swarm-based artificial machine intelligence technique coined SWAMI for voltage collapse minimization or prevention through dynamic shunt compensation of overloaded power network buses. Several simulation studies have been conducted considering three very popular and successful SWAMI agents – the PSOM, BCOM and ACOM on an IEEE benchmark power network with promising results. Simulation studies showed that the PSOM SWAMI exhibited the most stable response in terms of voltage profile collapse and recovery from voltage collapse state after voltage sensitivity studies. Safe margins of loading and optimal shunt compensations are determined based on the SWAMI techniques

    Kinetics of diffusion-controlled enzymatic reactions with charged substrates

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    The Debye-HĂŒckel limiting law (DHL) has often been used to estimate rate constants of diffusion-controlled reactions under different ionic strengths. Two main approximations are adopted in DHL: one is that the solution of the linearized Poisson-Boltzmann equation for a spherical cavity is used to estimate the excess electrostatic free energy of a solution; the other is that details of electrostatic interactions of the solutes are neglected. This makes DHL applicable only at low ionic strengths and dilute solutions (very low substrate/solute concentrations). We show in this work that through numerical solution of the Poisson-Nernst-Planck equations, diffusion-reaction processes can be studied at a variety of conditions including realistically concentrated solutions, high ionic strength, and certainly with non-equilibrium charge distributions. Reaction rate coefficients for the acetylcholine-acetylcholinesterase system are predicted to strongly depend on both ionic strength and substrate concentration. In particular, they increase considerably with increase of substrate concentrations at a fixed ionic strength, which is open to experimental testing. This phenomenon is also verified on a simple model, and is expected to be general for electrostatically attracting enzyme-substrate systems

    Incorporating Technology Into the iCook 4-H Program, a Cooking Intervention for Adults and Children: Randomized Controlled Trial

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    Background: Families who cook, eat, and play together have been found to have more positive health outcomes. Interventions are needed that effectively increase these health-related behaviors. Technology is often incorporated in health-related interventions but is not always independently assessed. Objective: The objective of this study was to describe challenges and facilitators to incorporating technology into the iCook 4-H intervention program. Methods: Dyads (n=228) composed of children (mean 9.4, SD 0.7 years old) and an adult primary meal preparer (mean 39.0, SD 8 years) were randomly assigned to a control (n=77) or treatment group (n=151). All treatment group dyads participated in 6 in-person sessions designed to increase families cooking, eating, and playing together. We incorporated Web-based between-session technological components related to the curriculum content throughout the intervention. Assessments were completed by both groups at baseline and at 4, 12, and 24 months; they included measured anthropometrics for children, and online surveys about camera and website skill and use for dyads. Session leaders and participants completed open-ended process evaluations after each session about technological components. We computed chi-square analysis for sex differences in technological variables. We tested relationships between video posting frequency and outcomes of interest (cooking frequency, self-efficacy, and skills; dietary intake; and body mass index) with Spearman correlations. Process evaluations and open-ended survey responses were thematically analyzed for beneficial and inhibiting factors, including technological components in the curriculum. Results: Only 78.6% (81/103) of children and 68.3% (71/104) of adults reported always being comfortable accessing the internet postintervention. Boys reported being more comfortable than girls with technological tasks (P\u3c.05). Children who posted more videos had a higher level of cooking skills at 4 months postintervention (r=.189, P=.05). Barriers to website usage reported most frequently by children were lack of accessibility, remembering, interactivity, motivation, time, and lack of parental encouragement. Conclusions: Incorporating technological supports, such as cameras and websites, into children’s programs may help produce improved outcomes. Identifying barriers to and patterns of technology usage need to be considered when developing future child health promotion interventions
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