2,322 research outputs found

    Simultaneous transcranial magnetic stimulation and single-neuron recording in alert non-human primates.

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    Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report new methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally perturbed by stimulation artifact in awake monkeys (Macaca mulatta). We recorded action potentials within ∼1 ms after 0.4-ms TMS pulses and observed changes in activity that differed significantly for active stimulation as compared with sham stimulation. This methodology is compatible with standard equipment in primate laboratories, allowing easy implementation. Application of these tools will facilitate the refinement of next generation TMS devices, experiments and treatment protocols

    Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

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    Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

    Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

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    The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

    Synergistic effect p-phenylenediamine and n,n diphenylthiourea on the electrochemical corrosion behaviour of mild steel in dilute acid media

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    Electrochemical studies of the synergistic effect of p-phenylenediamine and n,n diphenylthiourea (TPD) as corrosion inhibitor of mild steel in dilute sulphuric and hydrochloric acid through weight loss and potentiodynamic polarization at ambient temperature were performed. Experimental results showed the excellent performance of TPD with an optimal inhibition efficiency of 88.18 and 93.88 %in sulphuric and 87.42 and 87.15 %in hydrochloric acid from both tests at all concentration studied. Polarization studies show the compound to be a mixed-type inhibitor. Adsorption of deanol on the steel surface was observed to obey the Langmuir and Frumkin isotherm models. X-ray diffractometry confirmed the absence of corrosion products and complexes. Optical microscopy confirmed the selective inhibition property of TPD to be through chemical adsorption on the steel surfac

    Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

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    The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

    Observation of associated near-side and away-side long-range correlations in √sNN=5.02  TeV proton-lead collisions with the ATLAS detector

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    Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

    Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

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    The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

    Ratio of the Isolated Photon Cross Sections at \sqrt{s} = 630 and 1800 GeV

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    The inclusive cross section for production of isolated photons has been measured in \pbarp collisions at s=630\sqrt{s} = 630 GeV with the \D0 detector at the Fermilab Tevatron Collider. The photons span a transverse energy (ETE_T) range from 7-49 GeV and have pseudorapidity η<2.5|\eta| < 2.5. This measurement is combined with to previous \D0 result at s=1800\sqrt{s} = 1800 GeV to form a ratio of the cross sections. Comparison of next-to-leading order QCD with the measured cross section at 630 GeV and ratio of cross sections show satisfactory agreement in most of the ETE_T range.Comment: 7 pages. Published in Phys. Rev. Lett. 87, 251805, (2001

    Understanding patients' satisfaction with physician assistant/associate encounters through communication experiences: a qualitative study in acute hospitals in England.

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    BACKGROUND: Physician assistants/associates (PAs) are a recent innovation in acute hospital teams in England and many other countries worldwide. Although existing evidence indicates generally high levels of patient satisfaction with their PA hospital encounters, little is known about the factors associated with this outcome. There is a lack of evidence on the process of PA-patient communication in hospital encounters and how this might influence satisfaction. This study therefore aimed to understand patients' satisfaction with PA acute hospital encounters through PA-patient communication experiences. METHODS: A qualitative study was conducted among patients and representatives of patients seen by or receiving care from one of the PAs working in acute hospital services in England. Semi-structured interviews were undertaken face-to-face with study participants in the hospital setting and shortly after their PA encounter. Data were coded and analysed using thematic analysis. The study was framed within a theoretical model of core functions of medical encounter communication. RESULTS: Fifteen patients and patient representatives who had experienced a PA encounter participated in interviews, across five hospitals in England. Four interrelated communication experiences were important to participants who were satisfied with the encounter in general: feeling trust and confidence in the relationship, sharing relevant and meaningful information, experiencing emotional care and support, and sharing discussion on illness management and treatment. However, many participants misconceived PAs to be doctors, raising a potential risk of reduced trust in the PA relationship and negative implications for satisfaction with their PA encounter. Participants considered it beneficial that patients be informed about the PA role to prevent confusion. CONCLUSIONS: PA encounters offer a constructive example of successful clinician-patient communication experiences in acute hospital encounters from the patient's perspective. Study participants were generally naïve to the PA role. Hospital services and organisations introducing these mid-level or advanced care practitioner roles should consider giving attention to informing patients about the roles

    Complementary intestinal mucosa and microbiota responses to caloric restriction

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    The intestine is key for nutrient absorption and for interactions between the microbiota and its host. Therefore, the intestinal response to caloric restriction (CR) is thought to be more complex than that of any other organ. Submitting mice to 25% CR during 14 days induced a polarization of duodenum mucosa cell gene expression characterised by upregulation, and downregulation of the metabolic and immune/inflammatory pathways, respectively. The HNF, PPAR, STAT, and IRF families of transcription factors, particularly the Pparα and Isgf3 genes, were identified as potentially critical players in these processes. The impact of CR on metabolic genes in intestinal mucosa was mimicked by inhibition of the mTOR pathway. Furthermore, multiple duodenum and faecal metabolites were altered in CR mice. These changes were dependent on microbiota and their magnitude corresponded to microbial density. Further experiments using mice with depleted gut bacteria and CR-specific microbiota transfer showed that the gene expression polarization observed in the mucosa of CR mice is independent of the microbiota and its metabolites. The holistic interdisciplinary approach that we applied allowed us to characterize various regulatory aspects of the host and microbiota response to CR
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