3,129 research outputs found

    Learning the Repair Urgency for a Decision Support System for Tunnel Maintenance

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    The transport network in many countries relies on extended portions which run underground in tunnels. As tunnels age, repairs are required to prevent dangerous collapses. However repairs are expensive and will affect the operational efficiency of the tunnel. We present a decision support system (DSS) based on supervised machine learning methods that learns to predict the risk factor and the resulting repair urgency in the tunnel maintenance planning of a European national rail operator. The data on which the prototype has been built consists of 47 tunnels of varying lengths. For each tunnel, periodic survey inspection data is available for multiple years, as well as other data such as the method of construction of the tunnel. Expert annotations are also available for each 10m tunnel segment for each survey as to the degree of repair urgency which are used for both training and model evaluation. We show that good predictive power can be obtained and discuss the relative merits of a number of learning methods

    Activin/Nodal Inhibition Alone Accelerates Highly Efficient Neural Conversion from Human Embryonic Stem Cells and Imposes a Caudal Positional Identity

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    Background Neural conversion from human embryonic stem cells (hESCs) has been demonstrated in a variety of systems including chemically defined suspension culture, not requiring extrinsic signals, as well as in an adherent culture method that involves dual SMAD inhibition using Noggin and SB431542 (an inhibitor of activin/nodal signaling). Previous studies have also determined a role for activin/nodal signaling in development of the neural plate and anterior fate specification. We therefore sought to investigate the independent influence of SB431542 both on neural commitment of hESCs and positional identity of derived neural progenitors in chemically defined substrate-free conditions. Methodology/Principal Findings We show that in non-adherent culture conditions, treatment with SB431542 alone for 8 days is sufficient for highly efficient and accelerated neural conversion from hESCs with negligible mesendodermal, epidermal or trophectodermal contamination. In addition the resulting neural progenitor population has a predominantly caudal identity compared to the more anterior positional fate of non-SB431542 treated cultures. Finally we demonstrate that resulting neurons are electro-physiologically competent. Conclusions This study provides a platform for the efficient generation of caudal neural progenitors under defined conditions for experimental study

    Unraveling the developmental roadmap toward human brown adipose tissue

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    Increasing brown adipose tissue (BAT) mass and activation is a therapeutic strategy to treat obesity and complications. Obese and diabetic patients possess low amounts of BAT, so an efficient way to expand their mass is necessary. There is limited knowledge about how human BAT develops, differentiates, and is optimally activated. Accessing human BAT is challenging, given its low volume and anatomical dispersion. These constraints make detailed BAT-related developmental and functional mechanistic studies in humans virtually impossible. We have developed and characterized functionally and molecularly a new chemically defined protocol for the differentiation of human pluripotent stem cells (hPSCs) into brown adipocytes (BAs) that overcomes current limitations. This protocol recapitulates step by step the physiological developmental path of human BAT. The BAs obtained express BA and thermogenic markers, are insulin sensitive, and responsive to ÎČ-adrenergic stimuli. This new protocol is scalable, enabling the study of human BAs at early stages of development

    Directed differentiation of human induced pluripotent stem cells into functional cholangiocyte-like cells

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    The difficulty in isolating and propagating functional primary cholangiocytes is a major limitation in the study of biliary disorders and the testing of novel therapeutic agents. To overcome this problem, we have developed a platform for the differentiation of human pluripotent stem cells (hPSCs) into functional cholangiocyte-like cells (CLCs). We have previously reported that our 26-d protocol closely recapitulates key stages of biliary development, starting with the differentiation of hPSCs into endoderm and subsequently into foregut progenitor (FP) cells, followed by the generation of hepatoblasts (HBs), cholangiocyte progenitors (CPs) expressing early biliary markers and mature CLCs displaying cholangiocyte functionality. Compared with alternative protocols for biliary differentiation of hPSCs, our system does not require coculture with other cell types and relies on chemically defined conditions up to and including the generation of CPs. A complex extracellular matrix is used for the maturation of CLCs; therefore, experience in hPSC culture and 3D organoid systems may be necessary for optimal results. Finally, the capacity of our platform for generating large amounts of disease-specific functional cholangiocytes will have broad applications for cholangiopathies, in disease modeling and for screening of therapeutic compounds.This work was funded by ERC starting grant Relieve IMDs (L.V., N.R.F.H.), the Cambridge Hospitals National Institute for Health Research Biomedical Research Center (L.V., N.R.F.H., F.S.), the Evelyn trust (N.R.F.H.) and the EU Fp7 grant TissuGEN (M.C.d.B.). F.S. was supported by an Addenbrooke's Charitable Trust Clinical Research Training Fellowship and a joint MRC-Sparks Clinical Research Training Fellowship

    Across-arc geochemical variations in the Southern Volcanic Zone, Chile (34.5- 38.0°S): Constraints on Mantle Wedge and Input Compositions

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    Crustal assimilation (e.g. Hildreth and Moorbath, 1988) and/or subduction erosion (e.g. Stern, 1991; Kay et al., 2005) are believed to control the geochemical variations along the northern portion of the Chilean Southern Volcanic Zone. In order to evaluate these hypotheses, we present a comprehensive geochemical data set (major and trace elements and O-Sr-Nd-Hf-Pb isotopes) from Holocene primarily olivine-bearing volcanic rocks across the arc between 34.5-38.0°S, including volcanic front centers from Tinguiririca to Callaqui, the rear arc centers of Infernillo Volcanic Field, Laguna del Maule and Copahue, and extending 300 km into the backarc. We also present an equivalent data set for Chile Trench sediments outboard of this profile. The volcanic arc (including volcanic front and rear arc) samples primarily range from basalt to andesite/trachyandesite, whereas the backarc rocks are low-silica alkali basalts and trachybasalts. All samples show some characteristic subduction zone trace element enrichments and depletions, but the backarc samples show the least. Backarc basalts have higher Ce/Pb, Nb/U, Nb/Zr, and Ta/Hf, and lower Ba/Nb and Ba/La, consistent with less of a slab-derived component in the backarc and, consequently, lower degrees of mantle melting. The mantle-like Ύ18O in olivine and plagioclase phenocrysts (volcanic arc = 4.9-5.6 and backarc = 5.0-5.4 per mil) and lack of correlation between Ύ18O and indices of differentiation and other isotope ratios, argue against significant crustal assimilation. Volcanic arc and backarc samples almost completely overlap in Sr and Nd isotopic composition. High precision (double-spike) Pb isotope ratios are tightly correlated, precluding significant assimilation of older sialic crust but indicating mixing between a South Atlantic Mid Ocean-Ridge Basalt (MORB) source and a slab component derived from subducted sediments and altered oceanic crust. Hf-Nd isotope ratios define separate linear arrays for the volcanic arc and backarc, neither of which trend toward subducting sediment, possibly reflecting a primarily asthenospheric mantle array for the volcanic arc and involvement of enriched Proterozoic lithospheric mantle in the backarc. We propose a quantitative mixing model between a mixed-source, slab-derived melt and a heterogeneous mantle beneath the volcanic arc. The model is consistent with local geodynamic parameters, assuming water-saturated conditions within the slab

    Measurement of the relative rate of prompt χc0, χc1 and χc2 production at √s=7TeV

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    Prompt production of charmonium χc0, χc1 and χc2 mesons is studied using proton-proton collisions at the LHC at a centre-of-mass energy of √s=7TeV. The χc mesons are identified through their decay to J/ÏˆÎł, with J/ψ→Ό+mu− using photons that converted in the detector. A data sample, corresponding to an integrated luminosity of 1.0fb−1 collected by the LHCb detector, is used to measure the relative prompt production rate of χc1 and χc2 in the rapidity range 2.0<y<4.5 as a function of the J/ψ transverse momentum from 3 to 20 GeV/c. First evidence for χc0 meson production at a hadron collider is also presented

    Observation of two new Ξb−\Xi_b^- baryon resonances

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    Two structures are observed close to the kinematic threshold in the Ξb0π−\Xi_b^0 \pi^- mass spectrum in a sample of proton-proton collision data, corresponding to an integrated luminosity of 3.0 fb−1^{-1} recorded by the LHCb experiment. In the quark model, two baryonic resonances with quark content bdsbds are expected in this mass region: the spin-parity JP=12+J^P = \frac{1}{2}^+ and JP=32+J^P=\frac{3}{2}^+ states, denoted Ξbâ€Č−\Xi_b^{\prime -} and Ξb∗−\Xi_b^{*-}. Interpreting the structures as these resonances, we measure the mass differences and the width of the heavier state to be m(Ξbâ€Č−)−m(Ξb0)−m(π−)=3.653±0.018±0.006m(\Xi_b^{\prime -}) - m(\Xi_b^0) - m(\pi^{-}) = 3.653 \pm 0.018 \pm 0.006 MeV/c2/c^2, m(Ξb∗−)−m(Ξb0)−m(π−)=23.96±0.12±0.06m(\Xi_b^{*-}) - m(\Xi_b^0) - m(\pi^{-}) = 23.96 \pm 0.12 \pm 0.06 MeV/c2/c^2, Γ(Ξb∗−)=1.65±0.31±0.10\Gamma(\Xi_b^{*-}) = 1.65 \pm 0.31 \pm 0.10 MeV, where the first and second uncertainties are statistical and systematic, respectively. The width of the lighter state is consistent with zero, and we place an upper limit of Γ(Ξbâ€Č−)<0.08\Gamma(\Xi_b^{\prime -}) < 0.08 MeV at 95% confidence level. Relative production rates of these states are also reported.Comment: 17 pages, 2 figure

    Study of DJ meson decays to D+π−, D0π+ and D∗+π− final states in pp collisions

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    A study of D+π−, D0π+ and D∗+π− final states is performed using pp collision data, corresponding to an integrated luminosity of 1.0 fb−1, collected at a centre-of-mass energy of 7 TeV with the LHCb detector. The D1(2420)0 resonance is observed in the D∗+π− final state and the D∗2(2460) resonance is observed in the D+π−, D0π+ and D∗+π− final states. For both resonances, their properties and spin-parity assignments are obtained. In addition, two natural parity and two unnatural parity resonances are observed in the mass region between 2500 and 2800 MeV. Further structures in the region around 3000 MeV are observed in all the D∗+π−, D+π− and D0π+ final states

    Model-independent search for CP violation in D0→K−K+π−π+ and D0→π−π+π+π− decays

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    A search for CP violation in the phase-space structures of D0 and View the MathML source decays to the final states K−K+π−π+ and π−π+π+π− is presented. The search is carried out with a data set corresponding to an integrated luminosity of 1.0 fb−1 collected in 2011 by the LHCb experiment in pp collisions at a centre-of-mass energy of 7 TeV. For the K−K+π−π+ final state, the four-body phase space is divided into 32 bins, each bin with approximately 1800 decays. The p-value under the hypothesis of no CP violation is 9.1%, and in no bin is a CP asymmetry greater than 6.5% observed. The phase space of the π−π+π+π− final state is partitioned into 128 bins, each bin with approximately 2500 decays. The p-value under the hypothesis of no CP violation is 41%, and in no bin is a CP asymmetry greater than 5.5% observed. All results are consistent with the hypothesis of no CP violation at the current sensitivity
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