Systemic AAV vectors for widespread and targeted gene delivery in rodents

We recently developed adeno-associated virus (AAV) capsids to facilitate efficient and noninvasive gene transfer to the central and peripheral nervous systems. However, a detailed protocol for generating and systemically delivering novel AAV variants was not previously available. In this protocol, we describe how to produce and intravenously administer AAVs to adult mice to specifically label and/or genetically manipulate cells in the nervous system and organs, including the heart. The procedure comprises three separate stages: AAV production, intravenous delivery, and evaluation of transgene expression. The protocol spans 8 d, excluding the time required to assess gene expression, and can be readily adopted by researchers with basic molecular biology, cell culture, and animal work experience. We provide guidelines for experimental design and choice of the capsid, cargo, and viral dose appropriate for the experimental aims. The procedures outlined here are adaptable to diverse biomedical applications, from anatomical and functional mapping to gene expression, silencing, and editing

Charged-particle distributions at low transverse momentum in √s=13 13 TeV pp interactions measured with the ATLAS detector at the LHC

Measurements of distributions of charged particles produced in proton–proton collisions with a centre-of-mass energy of 13 TeV are presented. The data were recorded by the ATLAS detector at the LHC and correspond to an integrated luminosity of 151 μb −1 μb−1 . The particles are required to have a transverse momentum greater than 100 MeV and an absolute pseudorapidity less than 2.5. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the dependence of the mean transverse momentum on multiplicity are measured in events containing at least two charged particles satisfying the above kinematic criteria. The results are corrected for detector effects and compared to the predictions from several Monte Carlo event generators

Measurement of W+W− production in association with one jet in proton–proton collisions at sqrt(s) = 8TeV with the ATLAS detector

The production of W boson pairs in association with one jet in pp collisions at View the MathML sources=8 TeV is studied using data corresponding to an integrated luminosity of 20.3 fb−1 collected by the ATLAS detector during 2012 at the CERN Large Hadron Collider. The cross section is measured in a fiducial phase-space region defined by the presence of exactly one electron and one muon, missing transverse momentum and exactly one jet with a transverse momentum above 25 GeV and a pseudorapidity of |η|<4.5|η|<4.5. The leptons are required to have opposite electric charge and to pass transverse momentum and pseudorapidity requirements. The fiducial cross section is found to be View the MathML sourceσWWfid,1-jet=136±6(stat)±14(syst)±3(lumi) fb. In combination with a previous measurement restricted to leptonic final states with no associated jets, the fiducial cross section of WW production with zero or one jet is measured to be View the MathML sourceσWWfid,≤1-jet=511±9(stat)±26(syst)±10(lumi) fb. The ratio of fiducial cross sections in final states with one and zero jets is determined to be 0.36±0.050.36±0.05. Finally, a total cross section extrapolated from the fiducial measurement of WW production with zero or one associated jet is reported. The measurements are compared to theoretical predictions and found in good agreement

Search for doubly charged Higgs boson production in multi-lepton final states with the ATLAS detector using proton-proton collisions at √s = 13TeV

A search for doubly charged Higgs bosons with pairs of prompt, isolated, highly energetic leptons with the same electric charge is presented. The search uses a proton–proton collision data sample at a centre-of-mass energy of 13 TeV corresponding to 36.1 fb −1 of integrated luminosity recorded in 2015 and 2016 by the ATLAS detector at the LHC. This analysis focuses on the decays H±±→e±e±, H±±→e±μ± and H±±→μ±μ±, fitting the dilepton mass spectra in several exclusive signal regions. No significant evidence of a signal is observed and corresponding limits on the production cross-section and consequently a lower limit on m(H±±) are derived at 95% confidence level. With ℓ±ℓ±=e±e±/μ±μ±/e±μ±, the observed lower limit on the mass of a doubly charged Higgs boson only coupling to left-handed leptons varies from 770 to 870 GeV (850 GeV expected) for B(H±±→ℓ±ℓ±)=100% and both the expected and observed mass limits are above 450 GeV for B(H±±→ℓ±ℓ±)=10% and any combination of partial branching ratios

Search for dark matter at √s=13 TeV in final states containing an energetic photon and large missing transverse momentum with the ATLAS detector

Results of a search for physics beyond the Standard Model in events containing an energetic photon and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. As the number of events observed in data, corresponding to an integrated luminosity of 36.1 fb−1 of proton–proton collisions at a centre-of-mass energy of 13 TeV, is in agreement with the Standard Model expectations, model-independent limits are set on the fiducial cross section for the production of events in this final state. Exclusion limits are also placed in models where dark-matter candidates are pair-produced. For dark-matter production via an axial-vector or a vector mediator in the s-channel, this search excludes mediator masses below 750–1200 GeV for dark-matter candidate masses below 230–480 GeV at 95% confidence level, depending on the couplings. In an effective theory of dark-matter production, the limits restrict the value of the suppression scale M∗ to be above 790 GeV at 95% confidence level. A limit is also reported on the production of a high-mass scalar resonance by processes beyond the Standard Model, in which the resonance decays to Zγ and the Z boson subsequently decays into neutrinos

Measurements of the top quark branching ratios into channels with leptons and quarks with the ATLAS detector

We thank CERN for the very successful operation of the LHC, as well as the support staff from our institutions without whom ATLAS could not be operated efficiently. We acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWFW and FWF, Austria; ANAS, Azerbaijan; SSTC, Belarus; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; CONICYT, Chile; CAS, MOST and NSFC, China; COLCIENCIAS, Colombia; MSMT CR, MPO CR and VSC CR, Czech Republic; DNRF, DNSRC and Lundbeck Foundation, Denmark; EPLANET, ERC and NSRF, European Union; IN2P3-CNRS, CEA-DSM/IRFU, France; GNSF, Georgia; BMBF, DFG, HGF Helmholtz Association, MPG and AvH Foundation, Germany; GSRT and NSRF, Greece; RGC, Hong Kong SAR, China; ISF, MINERVA, GIF, I-CORE and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; FOM and NWO, Netherlands; BRF and RCN, Norway; MNiSW and NCN, Poland; GRICES and FCT, Portugal; MNE/IFA, Romania; MES of Russia and NRC KI, Russian Federation; JINR; MSTD, Serbia; MSSR, Slovakia; ARRS and MIZŠ, Slovenia; DST/NRF, South Africa; MINECO, Spain; SRC and Wallenberg Foundation, Sweden; SER, SNSF and Cantons of Bern and Geneva, Switzerland; NSC, Taiwan; TAEK, Turkey; STFC, the Royal Society and Leverhulme Trust, United Kingdom; DOE and NSF, United States of America. The crucial computing support from all WLCG partners is acknowledged gratefully, in particular from CERN and the ATLAS Tier-1 facilities at TRIUMF (Canada), NDGF (Denmark, Norway, Sweden), CC-IN2P3 (France), KIT/GridKA (Germany), INFN-CNAF (Italy), NL-T1 (Netherlands), PIC (Spain), ASGC (Taiwan), RAL (UK) and BNL (USA) and in the Tier-2 facilities worldwide

Determination of the ratio of b-quark fragmentation fractions fs/fd in pp collisions at √s = 7 TeV with the ATLAS Detector

With an integrated luminosity of 2.47  fb−1 recorded by the ATLAS experiment at the LHC, the exclusive decays B 0s→J/ψϕ and B0d→J/ψK*0 of B mesons produced in pp collisions at √s=7  TeV are used to determine the ratio of fragmentation fractions fs/fd. From the observed B0s→J/ψϕ and B0d→J/ψK*0 yields, the quantity (fs/fd)[B(B0s→J/ψϕ)/B(B 0d→J/ψK*0)] is measured to be 0.199±0.004(stat)±0.008(syst). Using a recent theory prediction for [B(B0s→J/ψϕ)/B(B0d→J/ψK*0)] yields (fs/fd)=0.240±0.004(stat)±0.010(syst)±0.017(th). This result is based on a new approach that provides a significant improvement of the world average

Searches for Higgs boson pair production in the hh→bbττ, γγWW∗, γγbb, bbbb channels with the ATLAS detector

Searches for both resonant and nonresonant Higgs boson pair production are performed in the hh→bbττ, γγWW∗ final states using 20.3  fb−1 of pp collision data at a center-of-mass energy of 8 TeV recorded with the ATLAS detector at the Large Hadron Collider. No evidence of their production is observed and 95% confidence-level upper limits on the production cross sections are set. These results are then combined with the published results of the hh→γγbb, bbbb analyses. An upper limit of 0.69 (0.47) pb on the nonresonant hh production is observed (expected), corresponding to 70 (48) times the SM gg→hh cross section. For production via narrow resonances, cross-section limits of hh production from a heavy Higgs boson decay are set as a function of the heavy Higgs boson mass. The observed (expected) limits range from 2.1 (1.1) pb at 260 GeV to 0.011 (0.018) pb at 1000 GeV. These results are interpreted in the context of two simplified scenarios of the Minimal Supersymmetric Standard Model

Muon reconstruction and identification efficiency in ATLAS using the full Run 2 pp collision data set at \sqrt{s}=13 TeV

This article documents the muon reconstruction and identification efficiency obtained by the ATLAS experiment for 139 \hbox {fb}^{-1} of pp collision data at \sqrt{s}=13 TeV collected between 2015 and 2018 during Run 2 of the LHC. The increased instantaneous luminosity delivered by the LHC over this period required a reoptimisation of the criteria for the identification of prompt muons. Improved and newly developed algorithms were deployed to preserve high muon identification efficiency with a low misidentification rate and good momentum resolution. The availability of large samples of Z\rightarrow \mu \mu and J/\psi \rightarrow \mu \mu decays, and the minimisation of systematic uncertainties, allows the efficiencies of criteria for muon identification, primary vertex association, and isolation to be measured with an accuracy at the per-mille level in the bulk of the phase space, and up to the percent level in complex kinematic configurations. Excellent performance is achieved over a range of transverse momenta from 3 GeV to several hundred GeV, and across the full muon detector acceptance of |\eta |<2.7

Measurements of differential cross-sections in top-quark pair events with a high transverse momentum top quark and limits on beyond the Standard Model contributions to top-quark pair production with the ATLAS detector at √s = 13 TeV

Cross-section measurements of top-quark pair production where the hadronically decaying top quark has transverse momentum greater than 355 GeV and the other top quark decays into ℓνb are presented using 139 fb−1 of data collected by the ATLAS experiment during proton-proton collisions at the LHC. The fiducial cross-section at s = 13 TeV is measured to be σ = 1.267 ± 0.005 ± 0.053 pb, where the uncertainties reflect the limited number of data events and the systematic uncertainties, giving a total uncertainty of 4.2%. The cross-section is measured differentially as a function of variables characterising the tt¯ system and additional radiation in the events. The results are compared with various Monte Carlo generators, including comparisons where the generators are reweighted to match a parton-level calculation at next-to-next-to-leading order. The reweighting improves the agreement between data and theory. The measured distribution of the top-quark transverse momentum is used to search for new physics in the context of the effective field theory framework. No significant deviation from the Standard Model is observed and limits are set on the Wilson coefficients of the dimension-six operators OtG and Otq(8), where the limits on the latter are the most stringent to date. [Figure not available: see fulltext.]