79 research outputs found

    Caveolin contributes to the modulation of basal and ÎČ-adrenoceptor stimulated function of the adult rat ventricular myocyte by simvastatin: A novel pleiotropic effect

    Get PDF
    The number of people taking statins is increasing across the globe, highlighting the Importance of fully understanding statins effects on the cardiovascular system. The beneficial impact of statins extends well beyond regression of atherosclerosis to include direct effects on tissues of the cardiovascular system (pleiotropic effects). Pleiotropic effects on the cardiac myocyte are often overlooked. Here we consider the contribution of the caveolin protein, whose expression and cellular distribution is dependent on cholesterol, to statin effects on the cardiac myocyte. Caveolin is a structural and regulatory component of caveolae, and is a key regulator of cardiac contractile function and adrenergic responsiveness. We employed an experimental model in which inhibition of myocyte HMG CoA reductase could be studied in the absence of paracrine influences from non-myocyte cells. Adult rat ventricular myocytes were treated with 10 ÎŒM simvastatin for 2 days. Simvastatin treatment reduced myocyte cholesterol, caveolin 3 and caveolar density. Negative inotropic and positive lusitropic effects (with corresponding changes in [Ca2]ÂĄ) were seen in statin-treated cells. Simvastatin significantly potentiated the inotropic response to ÎČ2-, but not ÎČ1-, adrenoceptor stimulation. Under conditions of ÎČ2-adrenoceptor stimulation, phosphorylation of phospholamban at Ser16and troponin I at Ser23/24was enhanced with statin treatment. Simvastatin increased NO production without significant effects on eNOS expression or phosphorylation (Ser1177), consistent with the reduced expression of caveolin 3, its constitutive Inhibitor. In conclusion, statin treatment can reduce caveolin 3 expression, with functional consequences consistent with the known role of caveolae in the cardiac cell. These data are likely to be of significance, particularly during the early phases of statin treatment, and in patients with heart failure who have altered ß-adrenoceptor signalling. In addition, as caveolin is ubiquitously expressed and has myriad tissue-specific functions, the impact of statin-dependent changes in caveolin is likely to have many other functional sequelae

    Measurement of the dependence of transverse energy production at large pseudorapidity on the hard-scattering kinematics of proton-proton collisions at √s=2.76 TeV with ATLAS

    Get PDF
    The relationship between jet production in the central region and the underlying-event activity in a pseudorapidity-separated region is studied in 4.0 pb-1 of s=2.76 TeV pp collision data recorded with the ATLAS detector at the LHC. The underlying event is characterised through measurements of the average value of the sum of the transverse energy at large pseudorapidity downstream of one of the protons, which are reported here as a function of hard-scattering kinematic variables. The hard scattering is characterised by the average transverse momentum and pseudorapidity of the two highest transverse momentum jets in the event. The dijet kinematics are used to estimate, on an event-by-event basis, the scaled longitudinal momenta of the hard-scattered partons in the target and projectile beam-protons moving toward and away from the region measuring transverse energy, respectively. Transverse energy production at large pseudorapidity is observed to decrease with a linear dependence on the longitudinal momentum fraction in the target proton and to depend only weakly on that in the projectile proton. The results are compared to the predictions of various Monte Carlo event generators, which qualitatively reproduce the trends observed in data but generally underpredict the overall level of transverse energy at forward pseudorapidity

    Measurements of the charge asymmetry in top-quark pair production in the dilepton final state at s √ =8  TeV with the ATLAS detector

    Get PDF
    Measurements of the top-antitop quark pair production charge asymmetry in the dilepton channel, characterized by two high-pT leptons (electrons or muons), are presented using data corresponding to an integrated luminosity of 20.3  fb−1 from pp collisions at a center-of-mass energy s√=8  TeV collected with the ATLAS detector at the Large Hadron Collider at CERN. Inclusive and differential measurements as a function of the invariant mass, transverse momentum, and longitudinal boost of the ttÂŻ system are performed both in the full phase space and in a fiducial phase space closely matching the detector acceptance. Two observables are studied: AℓℓC based on the selected leptons and AttÂŻC based on the reconstructed ttÂŻ final state. The inclusive asymmetries are measured in the full phase space to be AℓℓC=0.008±0.006 and AttÂŻC=0.021±0.016, which are in agreement with the Standard Model predictions of AℓℓC=0.0064±0.0003 and AttÂŻC=0.0111±0.0004

    Study of the B-c(+) -> J/psi D-s(+) and Bc(+) -> J/psi D-s*(+) decays with the ATLAS detector

    Get PDF
    The decays B-c(+) -> J/psi D-s(+) and B-c(+) -> J/psi D-s*(+) are studied with the ATLAS detector at the LHC using a dataset corresponding to integrated luminosities of 4.9 and 20.6 fb(-1) of pp collisions collected at centre-of-mass energies root s = 7 TeV and 8 TeV, respectively. Signal candidates are identified through J/psi -> mu(+)mu(-) and D-s(()*()+) -> phi pi(+)(gamma/pi(0)) decays. With a two-dimensional likelihood fit involving the B-c(+) reconstructed invariant mass and an angle between the mu(+) and D-s(+) candidate momenta in the muon pair rest frame, the yields of B-c(+) -> J/psi D-s(+) and B-c(+) -> J/psi D-s*(+), and the transverse polarisation fraction in B-c(+) -> J/psi D-s*(+) decay are measured. The transverse polarisation fraction is determined to be Gamma +/-+/-(B-c(+) -> J/psi D-s*(+))/Gamma(B-c(+) -> J/psi D-s*(+)) = 0.38 +/- 0.23 +/- 0.07, and the derived ratio of the branching fractions of the two modes is B-Bc+ -> J/psi D-s*+/B-Bc+ -> J/psi D-s(+) = 2.8(-0.8)(+1.2) +/- 0.3, where the first error is statistical and the second is systematic. Finally, a sample of B-c(+) -> J/psi pi(+) decays is used to derive the ratios of branching fractions B-Bc+ -> J/psi D-s*+/B-Bc+ -> J/psi pi(+) = 3.8 +/- 1.1 +/- 0.4 +/- 0.2 and B-Bc+ -> J/psi D-s*+/B-Bc+ -> J/psi pi(+) = 10.4 +/- 3.1 +/- 1.5 +/- 0.6, where the third error corresponds to the uncertainty of the branching fraction of D-s(+) -> phi(K+ K-)pi(+) decay. The available theoretical predictions are generally consistent with the measurement

    Measurement of W boson angular distributions in events with high transverse momentum jets at s√= 8 TeV using the ATLAS detector

    Get PDF
    The W boson angular distribution in events with high transverse momentum jets is measured using data collected by the ATLAS experiment from proton–proton collisions at a centre-of-mass energy at the Large Hadron Collider, corresponding to an integrated luminosity of . The focus is on the contributions to processes from real W emission, which is achieved by studying events where a muon is observed close to a high transverse momentum jet. At small angular separations, these contributions are expected to be large. Various theoretical models of this process are compared to the data in terms of the absolute cross-section and the angular distributions of the muon from the leptonic W decay.Fil: Aaboud, M.. UniversitĂ© Mohamed Premier and LPTPM; MarruecosFil: Aad, G.. Aix-Marseille UniversitĂ© ; FranciaFil: Abbott, B.. Oklahoma State University; Estados UnidosFil: Abdallah, J.. Academia Sinica; ChinaFil: Abdinov, O.. Azerbaijan Academy of Sciences; AzerbaiyĂĄnFil: Alconada Verzini, MarĂ­a Josefina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - La Plata. Instituto de FĂ­sica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de FĂ­sica La Plata; ArgentinaFil: Alonso, Francisco. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - La Plata. Instituto de FĂ­sica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de FĂ­sica La Plata; ArgentinaFil: Arduh, Francisco Anuar. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - La Plata. Instituto de FĂ­sica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de FĂ­sica La Plata; ArgentinaFil: Dova, Maria Teresa. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - La Plata. Instituto de FĂ­sica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de FĂ­sica La Plata; ArgentinaFil: Hoya, JoaquĂ­n. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - La Plata. Instituto de FĂ­sica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de FĂ­sica La Plata; ArgentinaFil: Monticelli, Fernando Gabriel. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - La Plata. Instituto de FĂ­sica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de FĂ­sica La Plata; ArgentinaFil: Wahlberg, Hernan Pablo. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - La Plata. Instituto de FĂ­sica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de FĂ­sica La Plata; ArgentinaFil: Bossio Sola, Jonathan David. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Ciudad Universitaria. Instituto de FĂ­sica de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de FĂ­sica de Buenos Aires; ArgentinaFil: Marceca, Gino. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Ciudad Universitaria. Instituto de FĂ­sica de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de FĂ­sica de Buenos Aires; ArgentinaFil: Otero y Garzon, Gustavo Javier. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Ciudad Universitaria. Instituto de FĂ­sica de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de FĂ­sica de Buenos Aires; ArgentinaFil: Piegaia, Ricardo Nestor. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Ciudad Universitaria. Instituto de FĂ­sica de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de FĂ­sica de Buenos Aires; ArgentinaFil: Sacerdoti, Sabrina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Ciudad Universitaria. Instituto de FĂ­sica de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de FĂ­sica de Buenos Aires; ArgentinaFil: Zibell. A.. Julius-Maximilians-UniversitĂ€t ; AlemaniaFil: Zieminska, D.. Indiana University; Estados UnidosFil: Zimine, N. I.. Joint Institute for Nuclear Research; RusiaFil: Zimmermann, C.. UniversitĂ€t Mainz ; AlemaniaFil: Zimmermann, S.. Albert-Ludwigs-UniversitĂ€t ; AlemaniaFil: Zinonos, Z.. Georg-August-UniversitĂ€t ; AlemaniaFil: Zinser, M.. UniversitĂ€t Mainz ; AlemaniaFil: Ziolkowski, M.. UniversitĂ€t Siegen ; AlemaniaFil: Ćœivković, L.. University of Belgrade ; SerbiaFil: Zobernig, G.. University of Wisconsin; Estados UnidosFil: Zoccoli, A.. UniversitĂ  di Bologna ; ItaliaFil: Nedden, M. zur. Humboldt University; AlemaniaFil: Zurzolo, G.. UniversitĂ  di Napoli; ItaliaFil: Zwalinski, L.. Cern - European Organization For Nuclear Research; SuizaFil: The ATLAS Collaboration. No especifica

    A TESS Dress Rehearsal: Planetary Candidates and Variables from K2 Campaign 17

    Get PDF
    We produce light curves for all ∌34,000 targets observed with K2 in Campaign 17 (C17), identifying planet candidates, eclipsing binaries, and other periodic variables. The forward-facing direction of the C17 field means follow-up can begin immediately now that the campaign has concluded and interesting targets have been identified. The C17 field has a large overlap with C6, so this latest campaign also offers an infrequent opportunity to study a large number of targets already observed in a previous K2 campaign. The timing of the C17 data release, shortly before science operations begin with the Transiting Exoplanet Survey Satellite (TESS), also lets us exercise some of the tools and methods developed for identification and dissemination of planet candidates from TESS. We find excellent agreement between these results and those identified using only K2-based tools. Among our planet candidates are several planet candidates with sizes <4 R ⊕ and orbiting stars with Kp â‰Č 10 (indicating good RV targets of the sort TESS hopes to find) and a Jupiter-sized single-transit event around a star already hosting a 6 day planet candidate

    Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

    Get PDF
    IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. EXPOSURES: Genetic test results. MAIN OUTCOMES AND MEASURES: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. RESULTS: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes

    A search for an excited muon decaying to a muon and two jets in pp collisions at √s = 8 TeV with the ATLAS detector

    Get PDF
    A new search signature for excited leptons is explored. Excited muons are sought in the channel pp→ΌΌ∗→ΌΌ jet jetpp \to \mu\mu^* \to \mu \mu\textrm{ jet jet}, assuming both the production and decay occur via a contact interaction. The analysis is based on 20.3 fb−1^{-1} of pppp collision data at a centre-of-mass energy of s\sqrt{s} = 8 TeV taken with the ATLAS detector at the Large Hadron Collider. No evidence of excited muons is found, and limits are set at the 95% confidence level on the cross section times branching ratio as a function of the excited-muon mass mΌ∗m_{\mu^*}. For mΌ∗m_{\mu^*} between 1.3 TeV and 3.0 TeV, the upper limit on σB(Ό∗→Όqqˉ\sigma B(\mu^* \to \mu q \bar{q}) is between 0.6 and 1 fb. Limits on σB\sigma B are converted to lower bounds on the compositeness scale Λ\Lambda. In the limiting case Λ=mΌ∗\Lambda = m_{\mu^*}, excited muons with a mass below 2.9 TeV are excluded. With the same model assumptions, these limits at larger Ό∗\mu^* masses improve upon previous limits from traditional searches based on the gauge-mediated decay ÎŒâˆ—â†’ÎŒÎł\mu^* \to \mu \gamma.Comment: 33 pages in total, author list starting page 16, 4 figures, 5 tables, final version published by New Journal of Physics including corrections in Erratum https://dx.doi.org/10.1088/1367-2630/ab46ed. All figures including auxiliary are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/EXOT-2015-0
    • 

    corecore