832 research outputs found

    Regulation and role of the PP2A-B56 holoenzyme family in cancer

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    Protein phosphatase 2A (PP2A) inactivation is common in cancer, leading to sustained activation of pro-survival and growth-promoting pathways. PP2A consists of a scaffolding A-subunit, a catalytic C-subunit, and a regulatory B-subunit. The functional complexity of PP2A holoenzymes arises mainly through the vast repertoire of regulatory B-subunits, which determine both their substrate specificity and their subcellular localization. Therefore, a major challenge for developing more effective therapeutic strategies for cancer is to identify the specific PP2A complexes to be targeted. Of note, the development of small molecules specifically directed at PP2A-B56α has opened new therapeutic avenues in both solid and hematological tumors. Here, we focus on the B56/PR61 family of PP2A regulatory subunits, which have a central role in directing PP2A tumor suppressor activity. We provide an overview of the mechanisms controlling the formation and regulation of these complexes, the pathways they control, and the mechanisms underlying their deregulation in cancer

    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

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    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

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    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

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    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

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    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

    Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries

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    Background: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. Aims: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. Methods: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). Results: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20–37) versus 47 (IQR 32–58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11–40]) than in HICs (44/102 [43%, 95% CI 34–53], p = 0.039). Conclusions: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.</p

    An embedding technique to determine ττ backgrounds in proton-proton collision data

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    An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe

    Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

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    A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

    Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

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    A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

    Search for Physics beyond the Standard Model in Events with Overlapping Photons and Jets

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    Results are reported from a search for new particles that decay into a photon and two gluons, in events with jets. Novel jet substructure techniques are developed that allow photons to be identified in an environment densely populated with hadrons. The analyzed proton-proton collision data were collected by the CMS experiment at the LHC, in 2016 at root s = 13 TeV, and correspond to an integrated luminosity of 35.9 fb(-1). The spectra of total transverse hadronic energy of candidate events are examined for deviations from the standard model predictions. No statistically significant excess is observed over the expected background. The first cross section limits on new physics processes resulting in such events are set. The results are interpreted as upper limits on the rate of gluino pair production, utilizing a simplified stealth supersymmetry model. The excluded gluino masses extend up to 1.7 TeV, for a neutralino mass of 200 GeV and exceed previous mass constraints set by analyses targeting events with isolated photons.Peer reviewe
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