pinecone/core-2020-05-10-deduplication huggingface dataset:
Anthocyanins do not influence long-chain n-3 fatty acid status: studies in cells, rodents and humans

AbstractIncreased tissue status of the long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) is associated with cardiovascular and cognitive benefits. Limited epidemiological and animal data suggest that flavonoids, and specifically anthocyanins, may increase EPA and DHA levels, potentially by increasing their synthesis from the shorter-chain n-3 PUFA, α-linolenic acid. Using complimentary cell, rodent and human studies we investigated the impact of anthocyanins and anthocyanin-rich foods/extracts on plasma and tissue EPA and DHA levels and on the expression of fatty acid desaturase 2 (FADS2), which represents the rate limiting enzymes in EPA and DHA synthesis. In experiment 1, rats were fed a standard diet containing either palm oil or rapeseed oil supplemented with pure anthocyanins for 8 weeks. Retrospective fatty acid analysis was conducted on plasma samples collected from a human randomized controlled trial where participants consumed an elderberry extract for 12 weeks (experiment 2). HepG2 cells were cultured with α-linolenic acid with or without select anthocyanins and their in vivo metabolites for 24 h and 48 h (experiment 3). The fatty acid composition of the cell membranes, plasma and liver tissues were analyzed by gas chromatography. Anthocyanins and anthocyanin-rich food intake had no significant impact on EPA or DHA status or FADS2 gene expression in any model system. These data indicate little impact of dietary anthocyanins on n-3 PUFA distribution and suggest that the increasingly recognized benefits of anthocyanins are unlikely to be the result of a beneficial impact on tissue fatty acid status
Rail–bridge coupling element of unequal lengths for analysing train–track–bridge interaction systems

AbstractThis paper presents a rail–bridge coupling element of unequal lengths, in which the length of a bridge element is longer than that of a rail element, to investigate the dynamic problem of train–track–bridge interaction systems. The equation of motion in matrix form is given for a train–track–bridge interaction system with the proposed element. The first two numerical examples with two types of bridge models are chosen to illustrate the application of the proposed element. The results show that, for the same length of rail element, (1) the dynamic responses of train, track and bridge obtained by the proposed element are almost identical to those obtained by the rail–bridge coupling element of equal length, and (2) compared with the rail–bridge coupling element of equal length, the proposed element can help to save computer time. Furthermore, the influence of the length of rail element on the dynamic responses of rail is significant. However, the influence of the length of rail element on the dynamic responses of bridge is insignificant. Therefore, the proposed element with a shorter rail element and a longer bridge element may be adopted to study the dynamic responses of a train–track–bridge interaction system. The last numerical example is to investigate the effects of two types of track models on the dynamic responses of vehicle, rail and bridge. The results show that: (1) there are differences of the dynamic responses of vehicle, rail and bridge based on the single-layer and double-layer track models, (2) the maximum differences increase with the increase of the mass of sleeper, (3) the double-layer track model is more accurate
Matching, sorting and wages

AbstractWe develop an empirical search-matching model which is suitable for analyzing the wage, employment and welfare impact of regulation in a labor market with heterogeneous workers and jobs. To achieve this we develop an equilibrium model of wage determination and employment which extends the current literature on equilibrium wage determination with matching and provides a bridge between some of the most prominent macro models and microeconometric research. The model incorporates productivity shocks, long-term contracts, on-the-job search and counter-offers. Importantly, the model allows for the possibility of assortative matching between workers and jobs due to complementarities between worker and job characteristics. We use the model to estimate the potential gain from optimal regulation and we consider the potential gains and redistributive impacts from optimal unemployment benefit policy. Here optimal policy is defined as that which maximizes total output and home production, accounting for the various constraints that arise from search frictions. The model is estimated on the NLSY using the method of moments
Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial

SummaryBackgroundLung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis.MethodsWe did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50–90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene–liposome complex or 0·9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867.FindingsBetween June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3·7%, 95% CI 0·1–7·3; p=0·046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups.InterpretationMonthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in efficacy and consistency of response to the current formulation are needed before gene therapy is suitable for clinical care; however, our findings should also encourage the rapid introduction of more potent gene transfer vectors into early phase trials.FundingMedical Research Council/National Institute for Health Research Efficacy and Mechanism Evaluation Programme
Evidence and belief in regulatory decisions – Incorporating expected utility into decision modelling

AbstractRecent changes in the assessment and management of risks has had the effect that greater importance has been placed on relationships between individuals and within groups to inform decision making. In this paper, we provide the theoretical underpinning for an expected utility approach to decision-making. The approach, which is presented using established evidence support logic (TESLA™), integrating the expected utilities in the forming of group decisions. The rationale and basis are described and illustrated through a hypothetical decision context of options for the disposal of animal carcasses that accumulate during disease outbreaks. The approach forms the basis for exploring the richness of risk-based decisions, and representing individual beliefs about the sufficiency of evidence they may advance in support of hypotheses
Cumulative effects of common genetic variants on risk of sudden cardiac death

AbstractBackgroundGenome-wide association studies and candidate-gene based approaches have identified multiple common variants associated with increased risk of sudden cardiac death (SCD). However, the independent contribution of these individual loci to disease risk is modest.ObjectiveTo investigate the cumulative effects of genetic variants previously associated with SCD risk.MethodsA total of 966 SCD cases from the Oregon-Sudden Unexpected Death Study and 1926 coronary artery disease controls from the Wellcome Trust Case–Control Consortium were investigated. We generated genetic risk scores (GRSs) for each trait composed of variants previously associated with SCD or with abnormalities in specific electrocardiographic traits such as QRS duration, QTc interval and heart rate. GRSs were calculated using a weighted approach based on the number of risk alleles weighted by the beta coefficients derived from the original studies. We also compared the highest and lowest quintiles for the GRS composed of SCD SNPs.ResultsIncreased cumulative risk was observed for a GRS composed of 14 SCD-SNPs (OR=1.17 [1.05–1.29], P=0.002). The risk for SCD was 1.5 fold greater in the highest risk quintile when compared to the lowest risk quintile (OR=1.46 [1.11–1.92]). We did not observe significant associations with SCD for SNPs that determine electrocardiographic traits.ConclusionsA modest but significant effect on SCD risk was identified for a GRS composed of 14 previously associated SCD SNPs. While next generation sequencing methodology will continue to identify additional novel variants, these findings represent proof of concept for the additive effects of gene variants on SCD risk
Ellipsoid Localization Microscopy Infers the Size and Order of Protein Layers in Bacillus Spore Coats

AbstractMultilayered protein coats are crucial to the dormancy, robustness, and germination of bacterial spores. In Bacillus subtilis spores, the coat contains over 70 distinct proteins. Identifying which proteins reside in each layer may provide insight into their distinct functions. We present image analysis methods that determine the order and geometry of concentric protein layers by fitting a model description for a spheroidal fluorescent shell image to optical micrographs of spores incorporating fluorescent fusion proteins. The radius of a spherical protein shell can be determined with <10 nm error by fitting an equation to widefield fluorescence micrographs. Ellipsoidal shell axes can be fitted with comparable precision. The layer orders inferred for B. subtilis and B. megaterium are consistent with measurements in the literature. The aspect ratio of elongated spores and the tendency of some proteins to localize near their poles can be quantified, enabling measurement of structural anisotropy
Natural X-ray lines from the low scale supersymmetry breaking

AbstractIn the supersymmetric models with low scale supersymmetry (SUSY) breaking where the gravitino mass is around keV, we show that the 3.5 keV X-ray lines can be explained naturally through several different mechanisms: (I) a keV scale dark gaugino plays the role of sterile neutrino in the presence of bilinear R-parity violation. Because the light dark gaugino obtains Majorana mass only via gravity mediation, it is a decaying warm dark matter (DM) candidate; (II) the compressed cold DM states, whose mass degeneracy is broken by gravity mediated SUSY breaking, emit such a line via the heavier one decay into the lighter one plus photon(s). A highly supersymmetric dark sector may readily provide such kind of system; (III) the light axino, whose mass again is around the gravitino mass, decays to neutrino plus gamma in the R-parity violating SUSY. Moreover, we comment on dark radiation from dark gaugino
Reinterpretation of Faddeev–Niemi knot in Skyrme theory

AbstractWe identify the Faddeev–Niemi knot in Skyrme theory as a vortex ring made of a helical baby skyrmion (a twisted chromomagnetic vortex which is periodic in z-coordinate) with the periodic ends connected together. This allows us to interpret the knot as two quantized magnetic flux rings linked together, the first one winding the second m times and the second one winding the first n times, whose linking number mn is fixed by the Chern–Simon index of the magnetic potential. This interpretation strongly suggests that the Skyrme theory could also describe a very interesting low energy physics in a completely different environment, which puts the theory in a totally new perspective
Nonlinear Zeno dynamics due to atomic interactions in Bose–Einstein condensate

AbstractWe show that nonlinear interactions induce both the Zeno and anti-Zeno effects in the generalized Bose–Josephson model (with the on-site interactions and the second-order tunneling) describing Bose–Einstein condensate in double-well trap subject to particle removal from one of the wells. We find that the on-site interactions induce only the Zeno effect, which appears at long evolution times, whereas the second-order tunneling leads to a strong decay of the atomic population at short evolution times, reminiscent of the anti-Zeno effect, and destroys the nonlinear Zeno effect due to the on-site interactions at long times
A Variant in MCF2L Is Associated with Osteoarthritis

Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease with a substantial public health impact. We used a 1000-Genomes-Project-based imputation in a genome-wide association scan for osteoarthritis (3177 OA cases and 4894 controls) to detect a previously unidentified risk locus. We discovered a small disease-associated set of variants on chromosome 13. Through large-scale replication, we establish a robust association with SNPs in MCF2L (rs11842874, combined odds ratio [95% confidence interval] 1.17 [1.11–1.23], p = 2.1 × 10−8) across a total of 19,041 OA cases and 24,504 controls of European descent. This risk locus represents the third established signal for OA overall. MCF2L regulates a nerve growth factor (NGF), and treatment with a humanized monoclonal antibody against NGF is associated with reduction in pain and improvement in function for knee OA patients
A Three-State Model with Loop Entropy for the Overstretching Transition of DNA

AbstractWe introduce a three-state model for a single DNA chain under tension that distinguishes among B-DNA, S-DNA, and M (molten or denatured) segments and at the same time correctly accounts for the entropy of molten loops, characterized by the exponent c in the asymptotic expression S ∼ –c ln n for the entropy of a loop of length n. Force extension curves are derived exactly by employing a generalized Poland-Scheraga approach and then compared to experimental data. Simultaneous fitting to force-extension data at room temperature and to the denaturation phase transition at zero force is possible and allows us to establish a global phase diagram in the force-temperature plane. Under a stretching force, the effects of the stacking energy (entering as a domain-wall energy between paired and unpaired bases) and the loop entropy are separated. Therefore, we can estimate the loop exponent c independently from the precise value of the stacking energy. The fitted value for c is small, suggesting that nicks dominate the experimental force extension traces of natural DNA
The affective modulation of motor awareness in anosognosia for hemiplegia: Behavioural and lesion evidence

AbstractThe possible role of emotion in anosognosia for hemiplegia (i.e., denial of motor deficits contralateral to a brain lesion), has long been debated between psychodynamic and neurocognitive theories. However, there are only a handful of case studies focussing on this topic, and the precise role of emotion in anosognosia for hemiplegia requires empirical investigation. In the present study, we aimed to investigate how negative and positive emotions influence motor awareness in anosognosia. Positive and negative emotions were induced under carefully-controlled experimental conditions in right-hemisphere stroke patients with anosognosia for hemiplegia (n = 11) and controls with clinically normal awareness (n = 10). Only the negative, emotion induction condition resulted in a significant improvement of motor awareness in anosognosic patients compared to controls; the positive emotion induction did not. Using lesion overlay and voxel-based lesion-symptom mapping approaches, we also investigated the brain lesions associated with the diagnosis of anosognosia, as well as with performance on the experimental task. Anatomical areas that are commonly damaged in AHP included the right-hemisphere motor and sensory cortices, the inferior frontal cortex, and the insula. Additionally, the insula, putamen and anterior periventricular white matter were associated with less awareness change following the negative emotion induction. This study suggests that motor unawareness and the observed lack of negative emotions about one's disabilities cannot be adequately explained by either purely motivational or neurocognitive accounts. Instead, we propose an integrative account in which insular and striatal lesions result in weak interoceptive and motivational signals. These deficits lead to faulty inferences about the self, involving a difficulty to personalise new sensorimotor information, and an abnormal adherence to premorbid beliefs about the body
Slow wave sleep and accelerated forgetting.

We investigated whether the benefit of slow wave sleep (SWS) for memory consolidation typically observed in healthy individuals is disrupted in people with accelerated long-term forgetting (ALF) due to epilepsy. SWS is thought to play an active role in declarative memory in healthy individuals and, furthermore, electrographic epileptiform activity is often more prevalent during SWS than during wakefulness or other sleep stages. We studied the relationship between SWS and the benefit of sleep for memory retention using a word-pair associates task. In both the ALF and the healthy control groups, sleep conferred a memory benefit. However, the relationship between the amount of SWS and sleep-related memory benefits differed significantly between the groups. In healthy participants, the amount of SWS correlated positively with sleep-related memory benefits. In stark contrast, the more SWS, the smaller the sleep-related memory benefit in the ALF group. Therefore, contrary to its role in healthy people, SWS-associated brain activity appears to be deleterious for memory in patients with ALF
Search for electroweak production of charginos and neutralinos in WH
  events in proton-proton collisions at sqrt(s) = 13 TeV

Results are reported from a search for physics beyond the standard model in
proton-proton collision events with a charged lepton (electron or muon), two
jets identified as originating from a bottom quark decay, and significant
imbalance in the transverse momentum. The search was performed using a data
sample corresponding to 35.9 inverse femtobarns, collected by the CMS
experiment in 2016 at sqrt(s) = 13 TeV. Events with this signature can arise,
for example, from the electroweak production of gauginos, which are predicted
in models based on supersymmetry. The event yields observed in data are
consistent with the estimated standard model backgrounds. Limits are obtained
on the cross sections for chargino-neutralino production in a simplified model
of supersymmetry with the decays chargino to W+/- lsp and neutralino to H lsp.
Values of m[chargino] between 220 and 490 GeV are excluded at 95% confidence
level by this search when the lsp is massless, and values of m[lsp] are
excluded up to 110 GeV for m[chargino] about 450 GeV.Comment: Replaced with the published version. Added the journal reference and
  DOI. All the figures and tables, including an additional supplemental table,
  can be found at
  http://cms-results.web.cern.ch/cms-results/public-results/publications/SUS-16-043
  (CMS Public Pages
The implementation of managed entry agreements in Central and Eastern Europe : findings and implications

Background: Managed entry agreements (MEAs) are a set of instruments to facilitate access to new medicines. This study surveyed the implementation of MEAs in Central and Eastern Europe (CEE) where limited comparative information is currently available. Method: We conducted a survey on the implementation of MEAs in CEE between January-March 2017. Results: Sixteen countries participated in this study. Across five countries with available data on the number of different MEA instruments implemented, the most common MEAs implemented were confidential discounts (n=495, 73%), followed by paybacks (n=92, 14%), price-volume agreements (n=37, 5%), free doses (n=25, 4%), bundle and other agreements (n=19, 3%), and payment by result (n=10, >1%). Across seven countries with data on MEAs by therapeutic group, the highest number of brand names associated with one or more MEA instruments belonged to the ATC-L group, antineoplastic and immunomodulating agents (n=201, 31%). The second most frequent therapeutic group for MEA implementation was ATC-A, alimentary tract and metabolism (n=87, 13%), followed by medicines for neurological conditions (n=83, 13%). Conclusion: Experience in implementing MEAs varied substantially across the region and there is considerable scope for greater transparency, sharing experiences and mutual learning. European citizens, authorities and industry should ask themselves whether within public health systems confidential discounts can still be tolerated, particularly when it is not clear which country and party they are really benefiting. Further, if MEAs are to improve access, countries should establish clear objectives for their implementation and a monitoring framework to measure their performance as well as the burden of implementation
Measurement of the Zγ production cross section in pp collisions at 8 TeV and search for anomalous triple gauge boson couplings

The cross section for the production of Zγ in proton-proton collisions at 8 TeV is measured based on data collected by the CMS experiment at the LHC corresponding to an integrated luminosity of 19.5 fb−1. Events with an oppositely-charged pair of muons or electrons together with an isolated photon are selected. The differential cross section as a function of the photon transverse momentum is measured inclusively and exclusively, where the exclusive selection applies a veto on central jets. The observed cross sections are compatible with the expectations of next-to-next-to-leading-order quantum chromodynamics. Limits on anomalous triple gauge couplings of ZZγ and Zγγ are set that improve on previous experimental results obtained with the charged lepton decay modes of the Z boson.The Scientific and Technical Research Council of Turkey, and Turkish Atomic Energy Authorit