515 research outputs found

    A brain-sparing diphtheria toxin for chemical genetic ablation of peripheral cell lineages.

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    Conditional expression of diphtheria toxin receptor (DTR) is widely used for tissue-specific ablation of cells. However, diphtheria toxin (DT) crosses the blood-brain barrier, which limits its utility for ablating peripheral cells using Cre drivers that are also expressed in the central nervous system (CNS). Here we report the development of a brain-sparing DT, termed BRAINSPAReDT, for tissue-specific genetic ablation of cells outside the CNS. We prevent blood-brain barrier passage of DT through PEGylation, which polarizes the molecule and increases its size. We validate BRAINSPAReDT with regional genetic sympathectomy: BRAINSPAReDT ablates peripheral but not central catecholaminergic neurons, thus avoiding the Parkinson-like phenotype associated with full dopaminergic depletion. Regional sympathectomy compromises adipose tissue thermogenesis, and renders mice susceptible to obesity. We provide a proof of principle that BRAINSPAReDT can be used for Cre/DTR tissue-specific ablation outside the brain using CNS drivers, while consolidating the link between adiposity and the sympathetic nervous system

    Compressed representation of a partially defined integer function over multiple arguments

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    In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

    Workshop to scope and preselect indicators for criterion D3C3 under MSFD decision (EU) 2017/848 (WKD3C3SCOPE)

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    The workshop to scope and preselect indicators for Descriptor 3 criterion 3 under MSFD Commission Decision (EU) 2017/848 (WKD3C3SCOPE) provided a platform for experts from the EU member states and relevant regional bodies to meet and support development and progress the assessment methodology, based on a request by the EC (DGENV). WKD3C3SCOPE is the first of a series of three workshops (WKD3C3THRESHOLDS and WKSIMULD3) to provide guidance in relation to operational indicators for MSFD D3C3. The workshop was organized as a series of presentations with intermittent group discussions. On the first day of the workshop the participants discussed what defines a ‘healthy population structure’ for species with different life history traits (ToR a). During the following days, the group discussed and identified relevant D3C3 indicators (ToR b) and developed criteria to select among the identified D3C3 indicators to allow further testing and setting of thresholds at WKD3C3THRESHOLDS (ToR c). The participants found that overall, healthy fish stocks are characterized by high productivity, wide age and size structuring in the population, and the ability to quickly recover from disturbances. The groups noted that environmental factors, along with stock biomass and fishing pressure, influence the productivity and health of a stock, with environment playing a particularly large role in the recruitment of short-lived stocks. It was suggested that the age structure of a stock might be more relevant for evaluating the health of long-lived stocks. However, it was acknowledged that not all stocks have sufficient data to evaluate all proposed indicators, and a single indicator is unlikely to suffice for all stocks. Data availability, species- specific factors and regional or sub-regional variation are thus also important considerations. In relation to ToR b, the participants presented their work on potential indicators including: recruitment time-series, proportion of fish larger than the mean size of first sexual maturation, F rec/Fbar, length distribution L 90, relative proportion of old fish above A 90, indicators of spawner quality, and SSB/R. A discussion on pros/cons, benefits to the population of high or low indicator values, benefits supported by empirical evidence, applicability to data-poor stocks and benefits supported by simulation/theoretical considerations followed the presentations. Finally, in relation to ToR c, the difficulty emerged in ranking the indicators alone without considering the data used to estimate them and a new set of evaluation criteria for use in WKD3C3THRESHOLDS were defined. Based on the outputs of the meeting a list of indicators to be further evaluated has been drafted, which also emphasizes the stocks for which studies have empirically demonstrated effects on productivity. In addition to the listed indicators, indicators of genetic diversity and proportion of fish with parasite infestation were mentioned but to the knowledge of the participants, widespread data for these are currently not publicly available.info:eu-repo/semantics/publishedVersio

    Precise determination of the mass of the Higgs boson and tests of compatibility of its couplings with the standard model predictions using proton collisions at 7 and 8 TeV

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    Peer reviewe

    Study of double parton scattering using W+2-jet events in proton-proton collisions at √s=7 TeV

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    Peer reviewe

    Search for new physics in the multijet and missing transverse momentum final state in proton-proton collisions at √s=8 Tev

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    Peer reviewe

    Measurement of the production cross section ratio σ(χb2(1P))/σ(χb1(1P))in pp collisions at √s=8TeV

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    A measurement of the production cross section ratio σ(χb2(1P))/σ(χb1(1P))σ(χb2(1P))/σ(χb1(1P)) is presented. The χb1(1P)χb1(1P) and χb2(1P)χb2(1P) bottomonium states, promptly produced in pp collisions at View the MathML sources=8 TeV, are detected by the CMS experiment at the CERN LHC through their radiative decays χb1,2(1P)→ϒ(1S)+γχb1,2(1P)→ϒ(1S)+γ. The emitted photons are measured through their conversion to e+e−e+e− pairs, whose reconstruction allows the two states to be resolved. The ϒ(1S)ϒ(1S) is measured through its decay to two muons. An event sample corresponding to an integrated luminosity of 20.7 fb−120.7 fb−1 is used to measure the cross section ratio in a phase-space region defined by the photon pseudorapidity, |ηγ|<1.0|ηγ|<1.0; the ϒ(1S)ϒ(1S) rapidity, |yϒ|<1.5|yϒ|<1.5; and the ϒ(1S)ϒ(1S) transverse momentum, View the MathML source7<pTϒ<40 GeV. The cross section ratio shows no significant dependence on the ϒ(1S)ϒ(1S) transverse momentum, with a measured average value of View the MathML source0.85±0.07(stat+syst)±0.08(BF), where the first uncertainty is the combination of the experimental statistical and systematic uncertainties and the second is from the uncertainty in the ratio of the χbχb branching fractions

    Search for the pair production of light top squarks in the e(+/-)mu(-/+) final state in proton-proton collisions at root s=13 TeV

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    A search for the production of a pair of top squarks at the LHC is presented. This search targets a region of parameter space where the kinematics of top squark pair production and top quark pair production are very similar, because of the mass difference between the top squark and the neutralino being close to the top quark mass. The search is performed with 35.9 fb(-1) of proton-proton collisions at a centre-of-mass energy of root s = 13 TeV, collected by the CMS detector in 2016, using events containing one electron-muon pair with opposite charge. The search is based on a precise estimate of the top quark pair background, and the use of the M-T2 variable, which combines the transverse mass of each lepton and the missing transverse momentum. No excess of events is found over the standard model predictions. Exclusion limits are placed at 95% confidence level on the production of top squarks up to masses of 208 GeV for models with a mass difference between the top squark and the lightest neutralino close to that of the top quark.Peer reviewe

    Measurement of B_{s}^{0} meson production in pp and PbPb collisions at \sqrt{SNN}

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    The production cross sections of B_{s}^{0} mesons and charge conjugates are measured in proton-proton (pp) and PbPb collisions via the exclusive decay channel B_{s}^{0}→J/ψϕ→μ^{+}μ^{−}K^{+}K^{−} at a center-of-mass energy of 5.02 TeV per nucleon pair and within the rapidity range |y|<2.4 using the CMS detector at the LHC. The pp measurement is performed as a function of transverse momentum (p_{T}) of the B_{s}^{0} mesons in the range of 7 to 50 GeV/c and is compared to the predictions of perturbative QCD calculations. The B_{s}^{0} production yield in PbPb collisions is measured in two p_{T} intervals, 7 to 15 and 15 to 50 GeV/c, and compared to the yield in pp collisions in the same kinematic region. The nuclear modification factor (R_{AA}) is found to be 1.5±0.6(stat)±0.5(syst) for 7–15 GeV/c, and 0.87±0.30(stat)±0.17(syst) for 15–50 GeV/c, respectively. Within current uncertainties, the B_{s}^{0} results are consistent with models of strangeness enhancement, and suppression by parton energy loss, as observed for the B+ mesons
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