A boundary exchange influence on deglacial neodymium isotope records from the deep western Indian Ocean

The use of neodymium (Nd) isotopes to reconstruct past water mass mixing relies upon the quasi-conservative behaviour of this tracer, whereas recent studies in the modern oceans have suggested that boundary exchange, involving the addition of Nd from ocean margin sediments, may be an important process in the Nd cycle. Here we suggest that the relative importance of water mass advection versus boundary exchange can be assessed where the deep western boundary current in the Indian Ocean flows past the Madagascan continental margin; a potential source of highly unradiogenic Nd. Foraminiferal coatings and bulk sediment reductive leachates are used to reconstruct bottom water Nd isotopic composition (εNd) in 8 Holocene age coretops, with excellent agreement between the two methods. These data record spatial variability of ∼4 εNd units along the flow path of Circumpolar Deep Water; εNd≈−8.8 in the deep southern inflow upstream of Madagascar, which evolves towards εNd≈−11.5 offshore northern Madagascar, whereas εNd≈−7.3 where deep water re-circulates in the eastern Mascarene Basin. This variability is attributed to boundary exchange and, together with measurements of detrital sediment εNd, an isotope mass balance suggests a deep water residence time for Nd of ≤400 yr along the Madagascan margin. Considering deglacial changes, a core in the deep inflow upstream of Madagascar records εNd changes that agree with previous reconstructions of the Circumpolar Deep Water composition in the Southern Ocean, consistent with a control by water mass advection and perhaps indicating a longer residence time for Nd in the open ocean away from local sediment inputs. In contrast, sites along the Madagascan margin record offset εNd values and reduced glacial–interglacial variability, underlining the importance of detecting boundary exchange before inferring water mass source changes from Nd isotope records. The extent of Madagascan boundary exchange appears to be unchanged between the Holocene and Late Glacial periods, while a consistent shift towards more radiogenic εNd values at all sites in the Late Glacial compared to the Holocene may represent a muted signal of a change in water mass source or composition

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

Budesonide orodispersible tablets maintain remission in a randomized, placebo-controlled trial of patients with eosinophilic esophagitis

Background & Aims: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder. Swallowed topical-acting corticosteroids are effective in bringing active EoE into remission. However, it is not clear whether these drugs are effective for long-term maintenance of remission. Methods: We performed a double-blind trial to compare the efficacy and safety of 2 dosages of a budesonide orodispersible tablet (BOT) vs placebo in maintaining remission of EoE. Maintenance of remission was defined as absence of clinical and histologic relapse and no premature withdrawal for any reason. Two hundred and four adults with EoE in clinical and histologic remission, from 29 European study sites, were randomly assigned to groups given BOT 0.5 mg twice daily (n = 68), BOT 1.0 mg twice daily (n = 68), or placebo twice daily (n = 68) for up to 48 weeks. Results: At end of treatment, 73.5% of patients receiving BOT 0.5 mg twice daily and 75% receiving BOT 1.0 mg twice daily were in persistent remission compared with 4.4% of patients in the placebo group (P < .001 for both comparisons of BOT with placebo). Median time to relapse in the placebo group was 87 days. The frequency of adverse events was similar in the BOT and placebo groups. Morning serum levels of cortisol were in the normal range at baseline and did not significantly change during treatment. Four patients receiving BOT developed asymptomatic, low serum levels of cortisol. Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5 mg group and in 11.8% of patients in the BOT 1.0 mg group; all infections resolved with treatment. Conclusions: In a phase 3 trial, up to 48 weeks of treatment with BOT (0.5 mg or 1.0 mg twice daily) was superior to placebo in maintaining remission of EoE. Both dosages were equally effective and well tolerated. EudraCT number; 2014-001485-99; ClinicalTrials.gov number, NCT02434029

A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)

We present a measurement of time-dependent CP-violating asymmetries in neutral B meson decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data sample consists of 29.7 ${\rm fb}^{-1}$ recorded at the $\Upsilon(4S)$ resonance and 3.9 ${\rm fb}^{-1}$ off-resonance. One of the neutral B mesons, which are produced in pairs at the $\Upsilon(4S)$, is fully reconstructed in the CP decay modes $J/\psi K^0_S$, $\psi(2S) K^0_S$, $\chi_{c1} K^0_S$, $J/\psi K^{*0}$ ($K^{*0}\to K^0_S\pi^0$) and $J/\psi K^0_L$, or in flavor-eigenstate modes involving $D^{(*)}\pi/\rho/a_1$ and $J/\psi K^{*0}$ ($K^{*0}\to K^+\pi^-$). The flavor of the other neutral B meson is tagged at the time of its decay, mainly with the charge of identified leptons and kaons. The proper time elapsed between the decays is determined by measuring the distance between the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample finds $\Delta m_d = 0.516\pm 0.016 {\rm (stat)} \pm 0.010 {\rm (syst)} {\rm ps}^{-1}$. The value of the asymmetry amplitude $\sin2\beta$ is determined from a simultaneous maximum-likelihood fit to the time-difference distribution of the flavor-eigenstate sample and about 642 tagged $B^0$ decays in the CP-eigenstate modes. We find $\sin2\beta=0.59\pm 0.14 {\rm (stat)} \pm 0.05 {\rm (syst)}$, demonstrating that CP violation exists in the neutral B meson system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Hierarchical coordination of periodic genes in the cell cycle of Saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>Gene networks are a representation of molecular interactions among genes or products thereof and, hence, are forming causal networks. Despite intense studies during the last years most investigations focus so far on inferential methods to reconstruct gene networks from experimental data or on their structural properties, e.g., degree distributions. Their structural analysis to gain functional insights into organizational principles of, e.g., pathways remains so far under appreciated.</p> <p>Results</p> <p>In the present paper we analyze cell cycle regulated genes in <it>S. cerevisiae</it>. Our analysis is based on the transcriptional regulatory network, representing causal interactions and not just associations or correlations between genes, and a list of known periodic genes. No further data are used. Partitioning the transcriptional regulatory network according to a graph theoretical property leads to a hierarchy in the network and, hence, in the information flow allowing to identify two groups of periodic genes. This reveals a novel conceptual interpretation of the working mechanism of the cell cycle and the genes regulated by this pathway.</p> <p>Conclusion</p> <p>Aside from the obtained results for the cell cycle of yeast our approach could be exemplary for the analysis of general pathways by exploiting the rich causal structure of inferred and/or curated gene networks including protein or signaling networks.</p

Measurement of the flavour composition of dijet events in pp collisions at root s=7 TeV with the ATLAS detector

This paper describes a measurement of the flavour composition of dijet events produced in pp collisions at &#8730;s=7 TeV using the ATLAS detector. The measurement uses the full 2010 data sample, corresponding to an integrated luminosity of 39 pb−1. Six possible combinations of light, charm and bottom jets are identified in the dijet events, where the jet flavour is defined by the presence of bottom, charm or solely light flavour hadrons in the jet. Kinematic variables, based on the properties of displaced decay vertices and optimised for jet flavour identification, are used in a multidimensional template fit to measure the fractions of these dijet flavour states as functions of the leading jet transverse momentum in the range 40 GeV to 500 GeV and jet rapidity |y|&#60;2.1. The fit results agree with the predictions of leading- and next-to-leading-order calculations, with the exception of the dijet fraction composed of bottom and light flavour jets, which is underestimated by all models at large transverse jet momenta. The ability to identify jets containing two b-hadrons, originating from e.g. gluon splitting, is demonstrated. The difference between bottom jet production rates in leading and subleading jets is consistent with the next-to-leading-order predictions

Influence of the Time Scale on the Construction of Financial Networks

BACKGROUND: In this paper we investigate the definition and formation of financial networks. Specifically, we study the influence of the time scale on their construction. METHODOLOGY/PRINCIPAL FINDINGS: For our analysis we use correlation-based networks obtained from the daily closing prices of stock market data. More precisely, we use the stocks that currently comprise the Dow Jones Industrial Average (DJIA) and estimate financial networks where nodes correspond to stocks and edges correspond to none vanishing correlation coefficients. That means only if a correlation coefficient is statistically significant different from zero, we include an edge in the network. This construction procedure results in unweighted, undirected networks. By separating the time series of stock prices in non-overlapping intervals, we obtain one network per interval. The length of these intervals corresponds to the time scale of the data, whose influence on the construction of the networks will be studied in this paper. CONCLUSIONS/SIGNIFICANCE: Numerical analysis of four different measures in dependence on the time scale for the construction of networks allows us to gain insights about the intrinsic time scale of the stock market with respect to a meaningful graph-theoretical analysis

Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0→D*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4  fb-1 collected at the Υ(4S) resonance during 1999–2000, we have reconstructed 38 candidate signal events in the mode B0→D*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0→D*+D*-)=[8.3±1.6(stat)±1.2(syst)]×10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation