The merger that led to the formation of the Milky Way's inner stellar halo and thick disk

The assembly process of our Galaxy can be retrieved using the motions and chemistry of individual stars. Chemo-dynamical studies of the nearby halo have long hinted at the presence of multiple components such as streams, clumps, duality and correlations between the stars' chemical abundances and orbital parameters. More recently, the analysis of two large stellar surveys have revealed the presence of a well-populated chemical elemental abundance sequence, of two distinct sequences in the colour-magnitude diagram, and of a prominent slightly retrograde kinematic structure all in the nearby halo, which may trace an important accretion event experienced by the Galaxy. Here report an analysis of the kinematics, chemistry, age and spatial distribution of stars in a relatively large volume around the Sun that are mainly linked to two major Galactic components, the thick disk and the stellar halo. We demonstrate that the inner halo is dominated by debris from an object which at infall was slightly more massive than the Small Magellanic Cloud, and which we refer to as Gaia-Enceladus. The stars originating in Gaia-Enceladus cover nearly the full sky, their motions reveal the presence of streams and slightly retrograde and elongated trajectories. Hundreds of RR Lyrae stars and thirteen globular clusters following a consistent age-metallicity relation can be associated to Gaia-Enceladus on the basis of their orbits. With an estimated 4:1 mass-ratio, the merger with Gaia-Enceladus must have led to the dynamical heating of the precursor of the Galactic thick disk and therefore contributed to the formation of this component approximately 10 Gyr ago. These findings are in line with simulations of galaxy formation, which predict that the inner stellar halo should be dominated by debris from just a few massive progenitors.Comment: 19 pages, 8 figures. Published in Nature in the issue of Nov. 1st, 2018. This is the authors' version before final edit

Cosmogenic neutron production at the Sudbury Neutrino Observatory

Neutrons produced in nuclear interactions initiated by cosmic-ray muons present an irreducible background to many rare-event searches, even in detectors located deep underground. Models for the production of these neutrons have been tested against previous experimental data, but the extrapolation to deeper sites is not well understood. Here we report results from an analysis of cosmogenically produced neutrons at the Sudbury Neutrino Observatory. A specific set of observables are presented, which can be used to benchmark the validity of geant4 physics models. In addition, the cosmogenic neutron yield, in units of 10-4 cm2/(g·μ), is measured to be 7.28±0.09(stat)-1.12+1.59(syst) in pure heavy water and 7.30±0.07(stat)-1.02+1.40(syst) in NaCl-loaded heavy water. These results provide unique insights into this potential background source for experiments at SNOLAB

Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The analysis was based on a search for gamma-rays from the de-excitation of the residual nucleus that would result from the disappearance of either a proton or neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90% confidence for either neutron or proton decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton decay modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of 2) Submitted to Physical Review Letter

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

Which resources should be used to identify RCT/CCTs for systematic reviews: a systematic review

BACKGROUND: Systematic reviewers seek to comprehensively search for relevant studies and summarize these to present the most valid estimate of intervention effectiveness. The more resources searched, the higher the yield, and thus time and costs required to conduct a systematic review. While there is an abundance of evidence to suggest how extensive a search for randomized controlled trials (RCTs) should be, it is neither conclusive nor consistent. This systematic review was conducted in order to assess the value of different resources to identify trials for inclusion in systematic reviews. METHODS: Seven electronic databases, four journals and Cochrane Colloquia were searched. Key authors were contacted and references of relevant articles screened. Included studies compared two or more sources to find RCTs or controlled clinical trials (CCTs). A checklist was developed and applied to assess quality of reporting. Data were extracted by one reviewer and checked by a second. Medians and ranges for precision and recall were calculated; results were grouped by comparison. Meta-analysis was not performed due to large heterogeneity. Subgroup analyses were conducted for: search strategy (Cochrane, Simple, Complex, Index), expertise of the searcher (Cochrane, librarian, non-librarian), and study design (RCT and CCT). RESULTS: Sixty-four studies representing 13 electronic databases met inclusion criteria. The most common comparisons were MEDLINE vs. handsearching (n = 23), MEDLINE vs. MEDLINE+handsearching (n = 13), and MEDLINE vs. reference standard (n = 13). Quality was low, particularly for the reporting of study selection methodology. Overall, recall and precision varied substantially by comparison and ranged from 0 to 100% and 0 to 99%, respectively. The trial registries performed the best with median recall of 89% (range 84, 95) and median precision of 96.5% (96, 97), although these results are based on a small number of studies. Inadequate or inappropriate indexing was the reason most cited for missing studies. Complex and Cochrane search strategies (SS) performed better than Simple SS. CONCLUSION: Multiple-source comprehensive searches are necessary to identify all RCTs for a systematic review, although indexing needs to be improved. Although trial registries demonstrated the highest recall and precision, the Cochrane SS or a Complex SS in consultation with a librarian are recommended. Continued efforts to develop CENTRAL should be supported

Structural motifs recurring in different folds recognize the same ligand fragments

<p>Abstract</p> <p>Background</p> <p>The structural analysis of protein ligand binding sites can provide information relevant for assigning functions to unknown proteins, to guide the drug discovery process and to infer relations among distant protein folds. Previous approaches to the comparative analysis of binding pockets have usually been focused either on the ligand or the protein component. Even though several useful observations have been made with these approaches they both have limitations. In the former case the analysis is restricted to binding pockets interacting with similar ligands, while in the latter it is difficult to systematically check whether the observed structural similarities have a functional significance.</p> <p>Results</p> <p>Here we propose a novel methodology that takes into account the structure of both the binding pocket and the ligand. We first look for local similarities in a set of binding pockets and then check whether the bound ligands, even if completely different, share a common fragment that can account for the presence of the structural motif. Thanks to this method we can identify structural motifs whose functional significance is explained by the presence of shared features in the interacting ligands.</p> <p>Conclusion</p> <p>The application of this method to a large dataset of binding pockets allows the identification of recurring protein motifs that bind specific ligand fragments, even in the context of molecules with a different overall structure. In addition some of these motifs are present in a high number of evolutionarily unrelated proteins.</p

Expression and activation of the oxytocin receptor in airway smooth muscle cells: Regulation by TNFα and IL-13

<p>Abstract</p> <p>Background</p> <p>During pregnancy asthma may remain stable, improve or worsen. The factors underlying the deleterious effect of pregnancy on asthma remain unknown. Oxytocin is a neurohypophyseal protein that regulates a number of central and peripheral responses such as uterine contractions and milk ejection. Additional evidence suggests that oxytocin regulates inflammatory processes in other tissues given the ubiquitous expression of the oxytocin receptor. The purpose of this study was to define the role of oxytocin in modulating human airway smooth muscle (HASMCs) function in the presence and absence of IL-13 and TNFα, cytokines known to be important in asthma.</p> <p>Method</p> <p>Expression of oxytocin receptor in cultured HASMCs was performed by real time PCR and flow cytomery assays. Responses to oxytocin was assessed by fluorimetry to detect calcium signals while isolated tracheal rings and precision cut lung slices (PCLS) were used to measure contractile responses. Finally, ELISA was used to compare oxytocin levels in the bronchoalveloar lavage (BAL) samples from healthy subjects and those with asthma.</p> <p>Results</p> <p>PCR analysis demonstrates that OXTR is expressed in HASMCs under basal conditions and that both interleukin (IL)-13 and tumor necrosis factor (TNFα) stimulate a time-dependent increase in OXTR expression at 6 and 18 hr. Additionally, oxytocin increases cytosolic calcium levels in fura-2-loaded HASMCs that were enhanced in cells treated for 24 hr with IL-13. Interestingly, TNFα had little effect on oxytocin-induced calcium response despite increasing receptor expression. Using isolated murine tracheal rings and PCLS, oxytocin also promoted force generation and airway narrowing. Further, oxytocin levels are detectable in bronchoalveolar lavage (BAL) fluid derived from healthy subjects as well as from those with asthma.</p> <p>Conclusion</p> <p>Taken together, we show that cytokines modulate the expression of functional oxytocin receptors in HASMCs suggesting a potential role for inflammation-induced changes in oxytocin receptor signaling in the regulation of airway hyper-responsiveness in asthma.</p

Cost-Effectiveness of Magnetic Resonance Imaging with a New Contrast Agent for the Early Diagnosis of Alzheimer's Disease

Background: Used as contrast agents for brain magnetic resonance imaging (MRI), markers for beta-amyloid deposits might allow early diagnosis of Alzheimer’s disease (AD). We evaluated the cost-effectiveness of such a diagnostic test, MRI+CLP (contrastophore-linker-pharmacophore), should it become clinically available. Methodology/Principal Findings: We compared the cost-effectiveness of MRI+CLP to that of standard diagnosis using currently available cognition tests and of standard MRI, and investigated the impact of a hypothetical treatment efficient in early AD. The primary analysis was based on the current French context for 70-year-old patients with Mild Cognitive Impairment (MCI). In alternative ‘‘screen and treat’ ’ scenarios, we analyzed the consequences of systematic screenings of over-60 individuals (either population-wide or restricted to the ApoE4 genotype population). We used a Markov model of AD progression; model parameters, as well as incurred costs and quality-of-life weights in France were taken from the literature. We performed univariate and probabilistic multivariate sensitivity analyses. The base-case preferred strategy was the standard MRI diagnosis strategy. In the primary analysis however, MRI+CLP could become the preferred strategy under a wide array of scenarios involving lower cost and/or higher sensitivity or specificity. By contrast, in the ‘‘screen and treat’’ analyses, the probability of MRI+CLP becoming the preferred strategy remained lower than 5%. Conclusions/Significance: It is thought that anti-beta-amyloid compounds might halt the development of dementia i

Measurement of neutron production in atmospheric neutrino interactions at the Sudbury Neutrino Observatory

Neutron production in GeV-scale neutrino interactions is a poorly studied process. We have measured the neutron multiplicities in atmospheric neutrino interactions in the Sudbury Neutrino Observatory experiment and compared them to the prediction of a Monte Carlo simulation using GENIE and a minimally modified version of GEANT4. We analyzed 837 days of exposure corresponding to Phase I, using pure heavy water, and Phase II, using a mixture of Cl in heavy water. Neutrons produced in atmospheric neutrino interactions were identified with an efficiency of $15.3\%$ and $44.3\%$, for Phase I and II respectively. The neutron production is measured as a function of the visible energy of the neutrino interaction and, for charged current quasi-elastic interaction candidates, also as a function of the neutrino energy. This study is also performed classifying the complete sample into two pairs of event categories: charged current quasi-elastic and non charged current quasi-elastic, and $\nu_{\mu}$ and $\nu_e$. Results show good overall agreement between data and Monte Carlo for both phases, with some small tension with a statistical significance below $2\sigma$ for some intermediate energies

A genome-wide association study of total child psychiatric problems scores.

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits