A2ML1 and otitis media: novel variants, differential expression, and relevant pathways

A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media

FUT2 Variants Confer Susceptibility to Familial Otitis Media

Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154∗) is associated with either risk for autoimmune diseases or protection against viral diarrhea and HIV. We determined the role of FUT2 in otitis media susceptibility by obtaining DNA samples from 609 multi-ethnic families and simplex case subjects with otitis media. Exome and Sanger sequencing, linkage analysis, and Fisher exact and transmission disequilibrium tests (TDT) were performed. The common FUT2 c.604C>T (p.Arg202∗) variant co-segregates with otitis media in a Filipino pedigree (LOD = 4.0). Additionally, a rare variant, c.412C>T (p.Arg138Cys), is associated with recurrent/chronic otitis media in European-American children (p = 1.2 × 10−5) and US trios (TDT p = 0.01). The c.461G>A (p.Trp154∗) variant was also over-transmitted in US trios (TDT p = 0.01) and was associated with shifts in middle ear microbiota composition (PERMANOVA p 20 were combined, FUT2 variants were over-transmitted in trios (TDT p = 0.001). Fut2 is transiently upregulated in mouse middle ear after inoculation with non-typeable Haemophilus influenzae. Four FUT2 variants—namely p.Ala104Val, p.Arg138Cys, p.Trp154∗, and p.Arg202∗—reduced A antigen in mutant-transfected COS-7 cells, while the nonsense variants also reduced FUT2 protein levels. Common and rare FUT2 variants confer susceptibility to otitis media, likely by modifying the middle ear microbiome through regulation of A antigen levels in epithelial cells. Our families demonstrate marked intra-familial genetic heterogeneity, suggesting that multiple combinations of common and rare variants plus environmental factors influence the individual otitis media phenotype as a complex trait

Search for resonances decaying into photon pairs in 139 fb−1 of pp collisions at √s = 13 TeV with the ATLAS detector

Searches for new resonances in the diphoton final state, with spin 0 as predicted by theories with an extended Higgs sector and with spin 2 using a warped extra-dimension benchmark model, are presented using 139 fb−1 of √s = 13 TeV pp collision data collected by the ATLAS experiment at the LHC. No significant deviation from the Standard Model is observed and upper limits are placed on the production cross-section times branching ratio to two photons as a function of the resonance mass

Measurement of the top-quark mass using a leptonic invariant mass in pp collisions at s√ = 13 TeV with the ATLAS detector

A measurement of the top-quark mass (mt) in the tt¯ → lepton + jets channel is presented, with an experimental technique which exploits semileptonic decays of b-hadrons produced in the top-quark decay chain. The distribution of the invariant mass mℓμ of the lepton, ℓ (with ℓ = e, μ), from the W-boson decay and the muon, μ, originating from the b-hadron decay is reconstructed, and a binned-template profile likelihood fit is performed to extract mt. The measurement is based on data corresponding to an integrated luminosity of 36.1 fb−1 of s√ = 13 TeV pp collisions provided by the Large Hadron Collider and recorded by the ATLAS detector. The measured value of the top-quark mass is mt = 174.41 ± 0.39 (stat.) ± 0.66 (syst.) ± 0.25 (recoil) GeV, where the third uncertainty arises from changing the PYTHIA8 parton shower gluon-recoil scheme, used in top-quark decays, to a recently developed setup

Search for single vector-like B quark production and decay via B → bH(b¯b) in pp collisions at √s = 13 TeV with the ATLAS detector

A search is presented for single production of a vector-like B quark decaying into a Standard Model b-quark and a Standard Model Higgs boson, which decays into a b¯b pair. The search is carried out in 139 fb−1 of √s = 13 TeV proton-proton collision data collected by the ATLAS detector at the LHC between 2015 and 2018. No significant deviation from the Standard Model background prediction is observed, and mass-dependent exclusion limits at the 95% confidence level are set on the resonance production cross-section in several theoretical scenarios determined by the couplings cW, cZ and cH between the B quark and the Standard Model W, Z and Higgs bosons, respectively. For a vector-like B occurring as an isospin singlet, the search excludes values of cW greater than 0.45 for a B resonance mass (mB) between 1.0 and 1.2 TeV. For 1.2 TeV < mB < 2.0 TeV, cW values larger than 0.50–0.65 are excluded. If the B occurs as part of a (B, Y) doublet, the smallest excluded cZ coupling values range between 0.3 and 0.5 across the investigated resonance mass range 1.0 TeV < mB < 2.0 TeV

Search for boosted diphoton resonances in the 10 to 70 GeV mass range using 138 fb−1 of 13 TeV pp collisions with the ATLAS detector

A search for diphoton resonances in the mass range between 10 and 70 GeV with the ATLAS experiment at the Large Hadron Collider (LHC) is presented. The analysis is based on pp collision data corresponding to an integrated luminosity of 138 fb−1 at a centre-of-mass energy of 13 TeV recorded from 2015 to 2018. Previous searches for diphoton resonances at the LHC have explored masses down to 65 GeV, finding no evidence of new particles. This search exploits the particular kinematics of events with pairs of closely spaced photons reconstructed in the detector, allowing examination of invariant masses down to 10 GeV. The presented strategy covers a region previously unexplored at hadron colliders because of the experimental challenges of recording low-energy photons and estimating the backgrounds. No significant excess is observed and the reported limits provide the strongest bound on promptly decaying axion-like particles coupling to gluons and photons for masses between 10 and 70 GeV

Evidence for the charge asymmetry in pp → tt¯ production at s√ = 13 TeV with the ATLAS detector

Inclusive and differential measurements of the top–antitop (tt¯) charge asymmetry Att¯C and the leptonic asymmetry Aℓℓ¯C are presented in proton–proton collisions at s√ = 13 TeV recorded by the ATLAS experiment at the CERN Large Hadron Collider. The measurement uses the complete Run 2 dataset, corresponding to an integrated luminosity of 139 fb−1, combines data in the single-lepton and dilepton channels, and employs reconstruction techniques adapted to both the resolved and boosted topologies. A Bayesian unfolding procedure is performed to correct for detector resolution and acceptance effects. The combined inclusive tt¯ charge asymmetry is measured to be Att¯C = 0.0068 ± 0.0015, which differs from zero by 4.7 standard deviations. Differential measurements are performed as a function of the invariant mass, transverse momentum and longitudinal boost of the tt¯ system. Both the inclusive and differential measurements are found to be compatible with the Standard Model predictions, at next-to-next-to-leading order in quantum chromodynamics perturbation theory with next-to-leading-order electroweak corrections. The measurements are interpreted in the framework of the Standard Model effective field theory, placing competitive bounds on several Wilson coefficients

Search for the Zγ decay mode of new high-mass resonances in pp collisions at √s = 13 TeV with the ATLAS detector

This letter presents a search for narrow, high-mass resonances in the Zγ final state with the Z boson decaying into a pair of electrons or muons. The √s = 13 TeV pp collision data were recorded by the ATLAS detector at the CERN Large Hadron Collider and have an integrated luminosity of 140 fb−1. The data are found to be in agreement with the Standard Model background expectation. Upper limits are set on the resonance production cross section times the decay branching ratio into Zγ. For spin-0 resonances produced via gluon–gluon fusion, the observed limits at 95% confidence level vary between 65.5 fb and 0.6 fb, while for spin-2 resonances produced via gluon–gluon fusion (or quark–antiquark initial states) limits vary between 77.4 (76.1) fb and 0.6 (0.5) fb, for the mass range from 220 GeV to 3400 GeV

Search for heavy resonances decaying into a Z or W boson and a Higgs boson in final states with leptons and b-jets in 139 fb−1 of pp collisions at s√ = 13 TeV with the ATLAS detector

This article presents a search for new resonances decaying into a Z or W boson and a 125 GeV Higgs boson h, and it targets the νν¯¯¯bb¯¯, ℓ+ℓ−bb¯¯, or ℓ±νbb¯¯ final states, where ℓ = e or μ, in proton-proton collisions at s√ = 13 TeV. The data used correspond to a total integrated luminosity of 139 fb−1 collected by the ATLAS detector during Run 2 of the LHC at CERN. The search is conducted by examining the reconstructed invariant or transverse mass distributions of Zh or Wh candidates for evidence of a localised excess in the mass range from 220 GeV to 5 TeV. No significant excess is observed and 95% confidence-level upper limits between 1.3 pb and 0.3 fb are placed on the production cross section times branching fraction of neutral and charged spin-1 resonances and CP-odd scalar bosons. These limits are converted into constraints on the parameter space of the Heavy Vector Triplet model and the two-Higgs-doublet model

The ATLAS trigger system for LHC Run 3 and trigger performance in 2022

The ATLAS trigger system is a crucial component of the ATLAS experiment at the LHC. It is responsible for selecting events in line with the ATLAS physics programme. This paper presents an overview of the changes to the trigger and data acquisition system during the second long shutdown of the LHC, and shows the performance of the trigger system and its components in the proton-proton collisions during the 2022 commissioning period as well as its expected performance in proton-proton and heavy-ion collisions for the remainder of the third LHC data-taking period (2022–2025)