21 research outputs found

    lincRNAs act in the circuitry controlling pluripotency and differentiation

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    Although thousands of large intergenic non-coding RNAs (lincRNAs) have been identified in mammals, few have been functionally characterized, leading to debate about their biological role. To address this, we performed loss-of-function studies on most lincRNAs expressed in mouse embryonic stem (ES) cells and characterized the effects on gene expression. Here we show that knockdown of lincRNAs has major consequences on gene expression patterns, comparable to knockdown of well-known ES cell regulators. Notably, lincRNAs primarily affect gene expression in trans. Knockdown of dozens of lincRNAs causes either exit from the pluripotent state or upregulation of lineage commitment programs. We integrate lincRNAs into the molecular circuitry of ES cells and show that lincRNA genes are regulated by key transcription factors and that lincRNA transcripts bind to multiple chromatin regulatory proteins to affect shared gene expression programs. Together, the results demonstrate that lincRNAs have key roles in the circuitry controlling ES cell state.Broad InstituteHarvard UniversityNational Human Genome Research Institute (U.S.)Merkin Family Foundation for Stem Cell Researc

    First measurement of neutrino oscillation parameters using neutrinos and antineutrinos by NOvA

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    The NOvA experiment has seen a 4.4σ signal of ν̄e appearance in a 2 GeV ν̄μ beam at a distance of 810 km. Using 12.33×1020 protons on target delivered to the Fermilab NuMI neutrino beamline, the experiment recorded 27 ν̄μ→ν̄e candidates with a background of 10.3 and 102 ν̄μ→ν̄μ candidates. This new antineutrino data are combined with neutrino data to measure the parameters |Δm322|=2.48-0.06+0.11×10-3 eV2/c4 and sin2θ23 in the ranges from (0.53-0.60) and (0.45-0.48) in the normal neutrino mass hierarchy. The data exclude most values near δCP=π/2 for the inverted mass hierarchy by more than 3σ and favor the normal neutrino mass hierarchy by 1.9σ and θ23 values in the upper octant by 1.6σ

    First measurement of neutrino oscillation parameters using neutrinos and antineutrinos by NOvA

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    The NOvA experiment has seen a 4.4 σ signal of ¯ ν e appearance in a 2 GeV ¯ ν μ beam at a distance of 810 km. Using 12.33 × 10 20 protons on target delivered to the Fermilab NuMI neutrino beamline, the experiment recorded 27 ¯ ν μ → ¯ ν e candidates with a background of 10.3 and 102 ¯ ν μ → ¯ ν μ candidates. This new antineutrino data are combined with neutrino data to measure the parameters | Δ m 2 32 | = 2.4 8 + 0.11 − 0.06 × 10 − 3     eV 2 / c 4 and sin 2 θ 23 in the ranges from (0.53–0.60) and (0.45–0.48) in the normal neutrino mass hierarchy. The data exclude most values near δ C P = π / 2 for the inverted mass hierarchy by more than 3 σ and favor the normal neutrino mass hierarchy by 1.9 σ and θ 23 values in the upper octant by 1.6 σ

    Measurement of neutrino-induced neutral-current coherent π0 production in the NOvA near detector

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    The cross section of neutrino-induced neutral-current coherent π0 production on a carbon-dominated target is measured in the NOvA near detector. This measurement uses a narrow-band neutrino beam with an average neutrino energy of 2.7 GeV, which is of interest to ongoing and future long-baseline neutrino oscillation experiments. The measured, flux-averaged cross section is σ=13.8±0.9(stat)±2.3(syst)×10−40cm2/nucleus, consistent with model prediction. This result is the most precise measurement of neutral-current coherent π0 production in the few-GeV neutrino energy region

    The Single-Phase ProtoDUNE Technical Design Report

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    ProtoDUNE-SP is the single-phase DUNE Far Detector prototype that is under construction and will be operated at the CERN Neutrino Platform (NP) starting in 2018. ProtoDUNE-SP, a crucial part of the DUNE effort towards the construction of the first DUNE 10-kt fiducial mass far detector module (17 kt total LAr mass), is a significant experiment in its own right. With a total liquid argon (LAr) mass of 0.77 kt, it represents the largest monolithic single-phase LArTPC detector to be built to date. It's technical design is given in this report

    Nanocomposites: synthesis, structure, properties and new application opportunities

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    The Single-Phase ProtoDUNE Technical Design Report

    Get PDF
    ProtoDUNE-SP is the single-phase DUNE Far Detector prototype that is under construction and will be operated at the CERN Neutrino Platform (NP) starting in 2018. ProtoDUNE-SP, a crucial part of the DUNE effort towards the construction of the first DUNE 10-kt fiducial mass far detector module (17 kt total LAr mass), is a significant experiment in its own right. With a total liquid argon (LAr) mass of 0.77 kt, it represents the largest monolithic single-phase LArTPC detector to be built to date. It's technical design is given in this report

    Functional impairment of the auditory pathway after perinatal asphyxia and the short-term effect of perinatal propofol anesthesia in lambs

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    BACKGROUND: Sensorineural hearing loss (SNHL) is a common feature in the postasphyxial syndrome in newborns. Several anesthetic drugs have been proposed to attenuate secondary neuronal injury elicited by hypoxia-ischemia. We hypothesized that propofol anesthesia reduces auditory impairment after perinatal asphyxia in comparison with isoflurane. METHODS: Twenty-three pregnant ewes were randomized to propofol or isoflurane anesthesia and sedation. The lambs underwent in utero umbilical cord occlusion (isoflurane n = 5; propofol n = 7) and were compared with sham-treated animals (isoflurane n = 5; propofol n = 6) at a gestational age of 133 d. For 8 h after delivery by cesarean section, repeated auditory brainstem responses (ABRs) were recorded to obtain hearing thresholds, peak amplitudes, latencies, and interpeak latencies. RESULTS: Significantly elevated mean thresholds, diminished amplitudes, and elevated latencies were observed in the asphyxia group relative to the control group through the observation period. Comparison of anesthetic treatment in the asphyxia group revealed a significantly lower elevation in threshold and less impairment in the ABR amplitudes and latencies during propofol anesthesia as compared with isoflurane anesthesia. CONCLUSION: Our results support the hypothesis that anesthesia with propofol has a preventive effect on the functional changes to the auditory pathway in the event of perinatal asphyxia
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