293 research outputs found

    A practical guide to conversation research: how to study what people say to each other

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    Conversation—a verbal interaction between two or more people—is a complex, pervasive, and consequential human behavior. Conversations have been studied across many academic disciplines. However, advances in recording and analysis techniques over the last decade have allowed researchers to more directly and precisely examine conversations in natural contexts and at a larger scale than ever before, and these advances open new paths to understand humanity and the social world. Existing reviews of text analysis and conversation research have focused on text generated by a single author (e.g., product reviews, news articles, and public speeches) and thus leave open questions about the unique challenges presented by interactive conversation data (i.e., dialogue). In this article, we suggest approaches to overcome common challenges in the workflow of conversation science, including recording and transcribing conversations, structuring data (to merge turn-level and speaker-level data sets), extracting and aggregating linguistic features, estimating effects, and sharing data. This practical guide is meant to shed light on current best practices and empower more researchers to study conversations more directly—to expand the community of conversation scholars and contribute to a greater cumulative scientific understanding of the social world

    PEITC-mediated inhibition of mRNA translation is associated with both inhibition of mTORC1 and increased eIF2α phosphorylation in established cell lines and primary human leukemia cells.

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    Increased mRNA translation drives carcinogenesis and is an attractive target for the development of new anti-cancer drugs. In this work, we investigated effects of phenethylisothiocyanate (PEITC), a phytochemical with chemopreventive and anti-cancer activity, on mRNA translation. PEITC rapidly inhibited global mRNA translation in human breast cancer-derived MCF7 cells and mouse embryonic fibroblasts (MEFs). In addition to the known inhibitory effects of PEITC on mTORC1 activity, we demonstrate that PEITC increased eIF2α phosphorylation. PEITC also increased formation of stress granules which are typically associated with eIF2α phosphorylation and accumulation of translationally stalled mRNAs. Analysis of genetically modified MEFs demonstrated that optimal inhibition of global mRNA translation by PEITC was dependent on eIF2α phosphorylation, but not mTORC1 inhibition. We extended this study into primary leukemic B cells derived from patients with chronic lymphocytic leukaemia (CLL). CLL cells were stimulated in vitro with anti-IgM to mimic binding of antigen, a major driver of this leukemia. In CLL cells, PEITC increased eIF2α phosphorylation, inhibited anti-IgM-induced mTORC1 activation and decreased both basal and anti-IgM-induced global mRNA translation. PEITC also inhibited transcription and translation of MYC mRNA and accumulation of the MYC oncoprotein, in anti-IgM-stimulated cells. Moreover, treatment of CLL cells with PEITC and the BTK kinase inhibitor ibrutinib decreased anti-IgM-induced translation and induced cell death to a greater extent than either agent alone. Therefore, PEITC can inhibit both global and mRNA specific translation (including MYC) via effects on multiple regulatory pathways. Inhibition of mRNA translation may contribute to the chemopreventive and anti-cancer effects of PEITC

    Physics case for an LHCb Upgrade II - Opportunities in flavour physics, and beyond, in the HL-LHC era

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    The LHCb Upgrade II will fully exploit the flavour-physics opportunities of the HL-LHC, and study additional physics topics that take advantage of the forward acceptance of the LHCb spectrometer. The LHCb Upgrade I will begin operation in 2020. Consolidation will occur, and modest enhancements of the Upgrade I detector will be installed, in Long Shutdown 3 of the LHC (2025) and these are discussed here. The main Upgrade II detector will be installed in long shutdown 4 of the LHC (2030) and will build on the strengths of the current LHCb experiment and the Upgrade I. It will operate at a luminosity up to 2×1034 cm−2s−1, ten times that of the Upgrade I detector. New detector components will improve the intrinsic performance of the experiment in certain key areas. An Expression Of Interest proposing Upgrade II was submitted in February 2017. The physics case for the Upgrade II is presented here in more depth. CP-violating phases will be measured with precisions unattainable at any other envisaged facility. The experiment will probe b → sl+l−and b → dl+l− transitions in both muon and electron decays in modes not accessible at Upgrade I. Minimal flavour violation will be tested with a precision measurement of the ratio of B(B0 → ÎŒ+Ό−)/B(Bs → ÎŒ+Ό−). Probing charm CP violation at the 10−5 level may result in its long sought discovery. Major advances in hadron spectroscopy will be possible, which will be powerful probes of low energy QCD. Upgrade II potentially will have the highest sensitivity of all the LHC experiments on the Higgs to charm-quark couplings. Generically, the new physics mass scale probed, for fixed couplings, will almost double compared with the pre-HL-LHC era; this extended reach for flavour physics is similar to that which would be achieved by the HE-LHC proposal for the energy frontier

    LHCb upgrade software and computing : technical design report

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    This document reports the Research and Development activities that are carried out in the software and computing domains in view of the upgrade of the LHCb experiment. The implementation of a full software trigger implies major changes in the core software framework, in the event data model, and in the reconstruction algorithms. The increase of the data volumes for both real and simulated datasets requires a corresponding scaling of the distributed computing infrastructure. An implementation plan in both domains is presented, together with a risk assessment analysis

    Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

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    Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a ZZ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 <pT<100< p_{\textrm{T}} < 100 GeV and in the pseudorapidity range 2.5<η<42.5 < \eta < 4. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb−1^{-1}. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

    Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

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    The decay B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} is studied in proton-proton collisions at a center-of-mass energy of s=13\sqrt{s}=13 TeV using data corresponding to an integrated luminosity of 5 fb−1\mathrm{fb}^{-1} collected by the LHCb experiment. In the Λc+K−\Lambda_{c}^+ K^{-} system, the Ξc(2930)0\Xi_{c}(2930)^{0} state observed at the BaBar and Belle experiments is resolved into two narrower states, Ξc(2923)0\Xi_{c}(2923)^{0} and Ξc(2939)0\Xi_{c}(2939)^{0}, whose masses and widths are measured to be m(Ξc(2923)0)=2924.5±0.4±1.1 MeV,m(Ξc(2939)0)=2938.5±0.9±2.3 MeV,Γ(Ξc(2923)0)=0004.8±0.9±1.5 MeV,Γ(Ξc(2939)0)=0011.0±1.9±7.5 MeV, m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV}, where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt Λc+K−\Lambda_{c}^{+} K^{-} sample. Evidence of a new Ξc(2880)0\Xi_{c}(2880)^{0} state is found with a local significance of 3.8 σ3.8\,\sigma, whose mass and width are measured to be 2881.8±3.1±8.5 MeV2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV} and 12.4±5.3±5.8 MeV12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}, respectively. In addition, evidence of a new decay mode Ξc(2790)0→Λc+K−\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-} is found with a significance of 3.7 σ3.7\,\sigma. The relative branching fraction of B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} with respect to the B−→D+D−K−B^{-} \to D^{+} D^{-} K^{-} decay is measured to be 2.36±0.11±0.22±0.252.36 \pm 0.11 \pm 0.22 \pm 0.25, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

    Shooting the messenger(RNA) in B-cell lymphoma

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    Systematic review of spontaneous reports of myocarditis and pericarditis in transplant recipients and immunocompromised patients following COVID-19 mRNA vaccination

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    Objectives To determine whether spontaneous reporting rates of myocarditis and pericarditis differed in immunocompromised patients compared with the whole population overall, and in terms of demographics, vaccine dose and time-to-onset.Design Systematic review of spontaneously reported data from the European Union/European Economic Area (EU/EEA), the USA and the UK.Data sources EudraVigilance (EU/EEA), Vaccine Adverse Event Reporting System (VAERS; USA) and the Medicines and Healthcare products Regulatory Agency (UK) spontaneous reporting databases were searched from date of vaccine launch to 1 December 2021.Eligibility criteria Publicly available spontaneous reporting data for ‘myocarditis’ and ‘pericarditis’ from EU/EEA and USA following COVID-19 messenger RNA vaccines. Reports with comorbidities or concurrent medication indicative of transplantation, HIV infection or cancer (‘immunocompromised’ population) were compared with each overall database population.Data extraction and synthesis Two researchers extracted data. Spontaneously reported events of myocarditis and pericarditis were presented for immunocompromised populations for each data source, stratified by age, sex, dose and time-to-onset (where available). Seriousness of each event was determined according to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Guideline E2A definition. Proportional reporting ratio (PRR) was calculated.Results There were 178 reports of myocarditis and pericarditis among immunocompromised individuals overall. Seriousness was comparable between the immunocompromised and overall populations in both databases. No trends in age or sex were observed among immunocompromised individuals. Most reports followed a second vaccine dose and occurred within 14 days. The frequency of reporting was similar to the wider population (PRR=1.36 (95% CI=0.89 to 1.82) for VAERS population).Conclusions Myocarditis and pericarditis following COVID-19 vaccination are very rare, and benefits of COVID-19 vaccination continue to outweigh any perceived risks. Reporting rates of myocarditis and pericarditis were similar in immunocompromised individuals, however defining characteristics differed compared with the whole population; therefore, continued monitoring of adverse events following vaccination remains vital to understand differences between population subgroups
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