247 research outputs found

    Revision of the DELFIC Particle Activity Module

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    The Defense Land Fallout Interpretive Code (DELFIC) was originally released in 1968 as a tool for modeling fallout patterns and for predicting exposure rates. Despite the continual advancement of knowledge of fission yields, decay behavior of fission products, and biological dosimetry, the decay data and logic of DELFIC have remained mostly unchanged since inception. Additionally, previous code revisions caused a loss of conservation of radioactive nuclides. In this report, a new revision of the decay database and the Particle Activity Module is introduced and explained. The database upgrades discussed are replacement of the fission yields with ENDF/B-VII data as formatted in the Oak Ridge Isotope Generation (ORIGEN) code, revised decay constants, revised exposure rate multipliers, revised decay modes and branching ratios, and revised boiling point data. Included decay logic upgrades represent a correction of a flaw in the treatment of the fission yields, extension of the logic to include more complex decay modes, conservation of nuclides (including stable nuclides) at all times, and conversion of key variables to double precision for nuclide conservation. Finally, recommended future work is discussed with an emphasis on completion of the overall radiation physics upgrade, particularly for dosimetry, induced activity, decay of the actinides, and fractionation

    Stable Force Balance between Epithelial Cells Arises from F-Actin Turnover

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    The propagation of force in epithelial tissues requires that the contractile cytoskeletal machinery be stably connected between cells through E-cadherin-containing adherens junctions. In many epithelial tissues, the cells’ contractile network is positioned at a distance from the junction. However, the mechanism or mechanisms that connect the contractile networks to the adherens junctions, and thus mechanically connect neighboring cells, are poorly understood. Here, we identified the role for F-actin turnover in regulating the contractile cytoskeletal network’s attachment to adherens junctions. Perturbing F-actin turnover via gene depletion or acute drug treatments that slow F-actin turnover destabilized the attachment between the contractile actomyosin network and adherens junctions. Our work identifies a critical role for F-actin turnover in connecting actomyosin to intercellular junctions, defining a dynamic process required for the stability of force balance across intercellular contacts in tissues.National Institute of General Medical Sciences (U.S.) (F32GM113425)National Institute of General Medical Sciences (U.S.) (R01GM084947)National Institute of General Medical Sciences (U.S.) (R01GM105984

    Free Water in White Matter Differentiates Mci and ad From Control Subjects

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    Recent evidence shows that neuroinflammation plays a role in many neurological diseases including mild cognitive impairment (MCI) and Alzheimer\u27s disease (AD), and that free water (FW) modeling from clinically acquired diffusion MRI (DTI-like acquisitions) can be sensitive to this phenomenon. This FW index measures the fraction of the diffusion signal explained by isotropically unconstrained water, as estimated from a bi-tensor model. In this study, we developed a simple but powerful whole-brain FW measure designed for easy translation to clinical settings and potential use as a priori outcome measure in clinical trials. These simple FW measures use a safe white matter (WM) mask without gray matter (GM)/CSF partial volume contamination

    Are Wearables Good or Bad for Society? An Exploration of Societal Benefits, Risks and Consequences of Augmented Reality Smart Glasses.

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    Recent market research forecasts predict that a new form of wearable devices will soon influence the media landscape: Augmented Reality Smart Glasses. While prior research highlights numerous potentials in personal and professional settings of smart glasses, this technology has also triggered several controversies in public discussions, for example, the risk of violating privacy and copyright laws. Yet, little research addresses the questions of whether smart glasses are good or bad for societies, and if yes, why. This study conducts exploratory research to contribute to narrowing this gap. Based on a survey among consumers, we identify several societal benefits and risks that determine consumers’ evaluation of the anticipated and desired success of smart glasses. These findings lead to numerous important implications for consumers, scholars, managers, and policy makers

    Lung function associated gene Integrator Complex subunit 12 regulates protein synthesis pathways

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    Background: Genetic studies of human lung function and Chronic Obstructive Pulmonary Disease have identified a highly significant and reproducible signal on 4q24. It remains unclear which of the two candidate genes within this locus may regulate lung function: GSTCD, a gene with unknown function, and/or INTS12, a member of the Integrator Complex which is currently thought to mediate 3'end processing of small nuclear RNAs.Results: We found that, in lung tissue, 4q24 polymorphisms associated with lung function correlate with INTS12 but not neighbouring GSTCD expression. In contrast to the previous reports in other species, we only observed a minor alteration of snRNA processing following INTS12 depletion. RNAseq analysis of knockdown cells instead revealed dysregulation of a core subset of genes relevant to airway biology and a robust downregulation of protein synthesis pathways. Consistent with this, protein translation was decreased in INTS12 knockdown cells. In addition, ChIPseq experiments demonstrated INTS12 binding throughout the genome, which was enriched in transcriptionally active regions. Finally, we defined the INTS12 regulome which includes genes belonging to the protein synthesis pathways.Conclusion: INTS12 has functions beyond the canonical snRNA processing. We show that it regulates translation by regulating the expression of genes belonging to protein synthesis pathways. This study provides a detailed analysis of INTS12 activities on a genome-wide scale and contributes to the biology behind the genetic association for lung function at 4q24.</p

    The Anglo-Saxon migration and the formation of the early English gene pool

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    The history of the British Isles and Ireland is characterized by multiple periods of major cultural change, including the influential transformation after the end of Roman rule, which precipitated shifts in language, settlement patterns and material culture1. The extent to which migration from continental Europe mediated these transitions is a matter of long-standing debate2–4. Here we study genome-wide ancient DNA from 460 medieval northwestern Europeans—including 278 individuals from England—alongside archaeological data, to infer contemporary population dynamics. We identify a substantial increase of continental northern European ancestry in early medieval England, which is closely related to the early medieval and present-day inhabitants of Germany and Denmark, implying large-scale substantial migration across the North Sea into Britain during the Early Middle Ages. As a result, the individuals who we analysed from eastern England derived up to 76% of their ancestry from the continental North Sea zone, albeit with substantial regional variation and heterogeneity within sites. We show that women with immigrant ancestry were more often furnished with grave goods than women with local ancestry, whereas men with weapons were as likely not to be of immigrant ancestry. A comparison with present- day Britain indicates that subsequent demographic events reduced the fraction of continental northern European ancestry while introducing further ancestry components into the English gene pool, including substantial southwestern European ancestry most closely related to that seen in Iron Age Franc

    Natural and Synthetic Polymers as Inhibitors of Drug Efflux Pumps

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    Inhibition of efflux pumps is an emerging approach in cancer therapy and drug delivery. Since it has been discovered that polymeric pharmaceutical excipients such as TweensÂŽ or PluronicsÂŽ can inhibit efflux pumps, various other polymers have been investigated regarding their potential efflux pump inhibitory activity. Among them are polysaccharides, polyethylene glycols and derivatives, amphiphilic block copolymers, dendrimers and thiolated polymers. In the current review article, natural and synthetic polymers that are capable of inhibiting efflux pumps as well as their application in cancer therapy and drug delivery are discussed

    An accurate and efficient identification of children with psychosocial problems by means of computerized adaptive testing

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    Background: Questionnaires used by health services to identify children with psychosocial problems are often rather short. The psychometric properties of such short questionnaires are mostly less than needed for an accurate distinction between children with and without problems. We aimed to assess whether a short Computerized Adaptive Test (CAT) can overcome the weaknesses of short written questionnaires when identifying children with psychosocial problems. Method: We used a Dutch national data set obtained from parents of children invited for a routine health examination by Preventive Child Healthcare with 205 items on behavioral and emotional problems (n = 2,041, response 84%). In a random subsample we determined which items met the requirements of an Item Response Theory (IRT) model to a sufficient degree. Using those items, item parameters necessary for a CAT were calculated and a cut-off point was defined. In the remaining subsample we determined the validity and efficiency of a Computerized Adaptive Test using simulation techniques, with current treatment status and a clinical score on the Total Problem Scale (TPS) of the Child Behavior Checklist as criteria. Results: Out of 205 items available 190 sufficiently met the criteria of the underlying IRT model. For 90% of the children a score above or below cut-off point could be determined with 95% accuracy. The mean number of items needed to achieve this was 12. Sensitivity and specificity with the TPS as a criterion were 0.89 and 0.91, respectively. Conclusion: An IRT-based CAT is a very promising option for the identification of psychosocial problems in children, as it can lead to an efficient, yet high-quality identification. The results of our simulation study need to be replicated in a real-life administration of this CAT
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