The cell line A-to-I RNA editing catalogue

Adenosine-to-inosine (A-to-I) RNA editing is a common post transcriptional modification. It has a critical role in protecting against false activation of innate immunity by endogenous double stranded RNAs and has been associated with various regulatory processes and diseases such as autoimmune and cardiovascular diseases as well as cancer. In addition, the endogenous A-to-I editing machinery has been recently harnessed for RNA engineering. The study of RNA editing in humans relies heavily on the usage of cell lines as an important and commonly-used research tool. In particular, manipulations of the editing enzymes and their targets are often developed using cell line platforms. However, RNA editing in cell lines behaves very differently than in normal and diseased tissues, and most cell lines exhibit low editing levels, requiring over-expression of the enzymes. Here, we explore the A-to-I RNA editing landscape across over 1000 human cell lines types and show that for almost every editing target of interest a suitable cell line that mimics normal tissue condition may be found. We provide CLAIRE, a searchable catalogue of RNA editing levels across cell lines available at http://srv00.recas.ba.infn.it/atlas/claire.html, to facilitate rational choice of appropriate cell lines for future work on A-to-I RNA editing

Impact hazard protection efficiency by a small kinetic impactor

In this paper the ability of a small kinetic impactor spacecraft to mitigate an Earth-threatening asteroid is assessed by means of a novel measure of efficiency. This measure estimates the probability of a space system to deflect a single randomly-generated Earth-impacting object to a safe distance from the Earth. This represents a measure of efficiency that is not biased by the orbital parameters of a test-case object. A vast number of virtual Earth-impacting scenarios are investigated by homogenously distributing in orbital space a grid of 17,518 Earth impacting trajectories. The relative frequency of each trajectory is estimated by means Opik’s theory and Bottke’s near Earth objects model. A design of the entire mitigation mission is performed and the largest deflected asteroid computed for each impacting trajectory. The minimum detectable asteroid can also be estimated by an asteroid survey model. The results show that current technology would likely suffice against discovered airburst and local damage threats, whereas larger space systems would be necessary to reliably tackle impact hazard from larger threats. For example, it is shown that only 1,000 kg kinetic impactor would suffice to mitigate the impact threat of 27.1% of objects posing similar threat than that posed by Apophis

The Determinants of Privatised Enterprise Performance in Russia

Using data from a large enterprise-level panel designed to address this issue, we account for enterprise performance in Russia. We link performance to four aspects of the economic environment: enterprise ownership; corporate governance; market structures and competition; and financial constraints. We conclude that private ownership and improved performance are not correlated, though restructuring is positively associated with the competitiveness of the market environment. These findings on private ownership support those of previous studies, e.g. Earle and Estrin (1997). Moreover, we find evidence that financially unconstrained firms are better in their undertaking of restructuring measures then financially constrained firms. Further analysis suggests that causality runs from restructuring to financial constraint, rather than the reverse. Finally, our findings indicate strong complementarities between the four factors influencing improved company performance, confirming the view that these factors need to be considered jointly.Privatisation, enterprise performance, competition, corporate governance, investment

The metaphysics of Machian frame-dragging

The paper investigates the kind of dependence relation that best portrays Machian frame-dragging in general relativity. The question is tricky because frame-dragging relates local inertial frames to distant distributions of matter in a time-independent way, thus establishing some sort of non-local link between the two. For this reason, a plain causal interpretation of frame-dragging faces huge challenges. The paper will shed light on the issue by using a generalized structural equation model analysis in terms of manipulationist counterfactuals recently applied in the context of metaphysical enquiry by Schaffer (2016) and Wilson (2017). The verdict of the analysis will be that frame-dragging is best understood in terms of a novel type of dependence relation that is half-way between causation and grounding

Mental Health Status and Perceived Barriers to Seeking Treatment in Rural Reserve Component Veterans

National Guard and Reserve (RC) troops (N=617) primarily from the Appalachian Region in Southwestern Pennsylvania who recently returned from deployment in support of current military conflicts responded to a survey that assessed their demographics, mental health symptoms, help-seeking behaviors, barriers for not seeking treatment, deployment history, and stressors. Veterans were classified as rural (N = 334) or non-rural (N = 283). Rural participants reported a significantly greater number of issues with transportation/access in seeking mental health treatment, were more likely to perceive others as worse off as a reason not to seek treatment, had a more negative attitude toward seeking treatment for mental health problems, and reported fewer concerns about a mental health problem affecting their career. Recommendations for mental health care providers and policymakers are offered based on the results, including the importance of recognizing the distinctive barriers to care that RC Appalachian veterans face when they come back into civilian communities, many of them rural

Enslaved Phase-Separation Fronts in One-Dimensional Binary Mixtures

Phase-separation fronts leave in their wakes morphologies that are substantially different from the morphologies formed in homogeneous phase-separation. In this paper we focus on fronts in binary mixtures that are enslaved phase-separation fronts, i.e. fronts that follow in the wake of a control-parameter front. In the one-dimensional case, which is the focus of this paper, the formed morphology is deceptively simple: alternating domains of a regular size. However, determining the size of these domains as a function of the front speed and other system parameters is a non-trivial problem. We present an analytical solution for the case where no material is deposited ahead of the front and numerical solutions and scaling arguments for more general cases. Through these enslaved phase-separation fronts large domains can be formed that are practically unattainable in homogeneous one-dimensional phase-separation

Mass modification of D-meson in hot hadronic matter

We evaluate the in-medium $D$ and $\bar D$-meson masses in hot hadronic matter induced by interactions with the light hadron sector described in a chiral SU(3) model. The effective Lagrangian approach is generalized to SU(4) to include charmed mesons. We find that the D-mass drops substantially at finite temperatures and densities, which open the channels of the decay of the charmonium states ($\Psi^\prime$, $\chi_c$, $J/\Psi$) to $D \bar D$ pairs in the thermal medium. The effects of vacuum polarisations from the baryon sector on the medium modification of the $D$-meson mass relative to those obtained in the mean field approximation are investigated. The results of the present work are compared to calculations based on the QCD sum-rule approach, the quark-meson coupling model, chiral perturbation theory, as well as to studies of quarkonium dissociation using heavy quark potential from lattice QCD.Comment: 18 pages including 7 figures, minor revision of the text, figure styles modified, to appear in Phys. Rev.

A measurement of CMB cluster lensing with SPT and DES year 1 data

Clusters of galaxies gravitationally lens the cosmic microwave background (CMB) radiation, resulting in a distinct imprint in the CMB on arcminute scales. Measurement of this effect offers a promising way to constrain the masses of galaxy clusters, particularly those at high redshift. We use CMB maps from the South Pole Telescope Sunyaev–Zel'dovich (SZ) survey to measure the CMB lensing signal around galaxy clusters identified in optical imaging from first year observations of the Dark Energy Survey. The cluster catalogue used in this analysis contains 3697 members with mean redshift of z = 0.45. We detect lensing of the CMB by the galaxy clusters at 8.1σ significance. Using the measured lensing signal, we constrain the amplitude of the relation between cluster mass and optical richness to roughly 17 percent precision, finding good agreement with recent constraints obtained with galaxy lensing. The error budget is dominated by statistical noise but includes significant contributions from systematic biases due to the thermal SZ effect and cluster miscentring

Monte-Carlo simulation with FLUKA for liquid and solid targets

Introduction Monte-Carlo simulations can be used to assess isotope production on small medical cyclotrons. These simulations calculate the particle interactions with electric and magnetic fields, as well as the nuclear reactions. The results can be used to predict both yields and isotopic contaminations and can aid in the optimum design of target material and target geometry [1,2]. FLUKA is a general-purpose tool widely used in many applications from accelerator shielding to target design, calorimetry, activation, dosimetry, detector design, neutrino physics, or radiotherapy [3,4]. In this work, we applied the Monte-Carlo code FLUKA to determine the accuracy of predicting yields of various isotopes as compared to experimental yields. Material and Methods The proton beam collimation system, as well as the liquid and solid target of the TR13 cyclotron at TRIUMF, has been modeled in FLUKA. The proton beam parameters were initially taken from the cyclotron design specifications and were optimized against experimental measurements from the TR13. Data from irradiations of different targets and with different beam currents were collected in order to account for average behavior, see FIG. 1. Yields for a pencil proton beam as well as a beam spread out in direction and energy have been calculated and have been compared to experimental results obtained with the TR13. Results and Conclusion The reactions listed in TABLE 1 were assessed. For most reactions a good agreement was found in the comparison between experimental and simulated saturation yield. TABLE 1 only shows the yields simulated with a proton beam with a spread in both direction and energy. In most cases, the simulated yield is slightly larger or comparable. Only the calculated yield for 55Co was significantly lower by a factor of 4.2. This is still a good agreement considering that FLUKA was originally a high-energy physics code. It may indicate that the FLUKA internal cross-section calculation for this isotope production needs some optimization. In summary, we conclude that FLUKA can be used as a tool for the prediction of isotope production as well as for target design

Rapid and substantial increases in anticoagulant use and expenditure in Australia following the introduction of new types of oral anticoagulants

© 2018 Morgan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objectives To quantify changes in anticoagulant use in Australia since the introduction of Non-vitamin K antagonist anticoagulants (NOACs) and to estimate government expenditure. Design Interrupted-time-series analysis quantifying anticoagulant dispensing, before and after first Pharmaceutical Benefits Scheme (PBS) NOAC listing in August 2009 for venous thromboembolism prevention; and expanded listing for stroke prevention in non-valvular atrial fibrillation (AF) in August 2013, up to June 2016. Estimated government expenditure on PBS-listed anticoagulants. Setting and participants PBS dispensing in 10% random sample of Australians, restricted to continuous concessional beneficiaries dispensed oral anticoagulants from July 2005 to June 2016. Total PBS anticoagulant expenditure was calculated using Medicare Australia statistics. Main outcome measures Monthly dispensing and initiation of oral anticoagulants (warfarin, rivaroxaban, dabigatran or apixaban). Annual PBS anticoagulant expenditure. Results An estimated 149,180 concessional beneficiaries were dispensed anticoagulants (100% warfarin) during July 2005. This increased to 292,550 during June 2016, of whom 47.0%, 27.1%, 18.7% and 7.2% were dispensed warfarin, rivaroxaban, apixaban and dabigatran, respectively. Of 16,500 initiated on anticoagulants in June 2016, 24.3%, 38.2%, 30.0% and 7.5% were initiated on warfarin, rivaroxaban, apixaban, and dabigatran, respectively. Compared to July 2005-July 2013, from August 2013-June 2016, dispensings for all anticoagulants increased by 2,303 dispensings/month (p<0.001, 95%CI = [1,229 3,376]); warfarin dispensing decreased by 1,803 dispensings/month (p<0.001, 95%CI = [–2,606, –1,000]). Total PBS anticoagulant expenditure was $19.5 million (97.0$203.3 million (86.2% concessional) in 2015/16, of which 11.2% was warfarin. Conclusions The introduction of the NOACs led to substantial increases in anticoagulant use and expenditure in Australia