The epithelial cholinergic system of the airways

Acetylcholine (ACh), a classical transmitter of parasympathetic nerve fibres in the airways, is also synthesized by a large number of non-neuronal cells, including airway surface epithelial cells. Strongest expression of cholinergic traits is observed in neuroendocrine and brush cells but other epithelial cell types—ciliated, basal and secretory—are cholinergic as well. There is cell type-specific expression of the molecular pathways of ACh release, including both the vesicular storage and exocytotic release known from neurons, and transmembrane release from the cytosol via organic cation transporters. The subcellular distribution of the ACh release machineries suggests luminal release from ciliated and secretory cells, and basolateral release from neuroendocrine cells. The scenario as known so far strongly suggests a local auto-/paracrine role of epithelial ACh in regulating various aspects on the innate mucosal defence mechanisms, including mucociliary clearance, regulation of macrophage function and modulation of sensory nerve fibre activity. The proliferative effects of ACh gain importance in recently identified ACh receptor disorders conferring susceptibility to lung cancer. The cell type-specific molecular diversity of the epithelial ACh synthesis and release machinery implies that it is differently regulated than neuronal ACh release and can be specifically targeted by appropriate drugs

Human Embryonic and Rat Adult Stem Cells with Primitive Endoderm-Like Phenotype Can Be Fated to Definitive Endoderm, and Finally Hepatocyte-Like Cells

Stem cell-derived hepatocytes may be an alternative cell source to treat liver diseases or to be used for pharmacological purposes. We developed a protocol that mimics mammalian liver development, to differentiate cells with pluripotent characteristics to hepatocyte-like cells. The protocol supports the stepwise differentiation of human embryonic stem cells (ESC) to cells with characteristics of primitive streak (PS)/mesendoderm (ME)/definitive endoderm (DE), hepatoblasts, and finally cells with phenotypic and functional characteristics of hepatocytes. Remarkably, the same protocol can also differentiate rat multipotent adult progenitor cells (rMAPCs) to hepatocyte-like cells, even though rMAPC are isolated clonally from cultured rat bone marrow (BM) and have characteristics of primitive endoderm cells. A fraction of rMAPCs can be fated to cells expressing genes consistent with a PS/ME/DE phenotype, preceding the acquisition of phenotypic and functional characteristics of hepatocytes. Although the hepatocyte-like progeny derived from both cell types is mixed, between 10–20% of cells are developmentally consistent with late fetal hepatocytes that have attained synthetic, storage and detoxifying functions near those of adult hepatocytes. This differentiation protocol will be useful for generating hepatocyte-like cells from rodent and human stem cells, and to gain insight into the early stages of liver development

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

Study of the spin and parity of the Higgs boson in diboson decays with the ATLAS detector

Studies of the spin, parity and tensor couplings of the Higgs boson in the H→ZZ∗→4ℓ, H→WW∗→eνμν and H→γγ decay processes at the LHC are presented. The investigations are based on 25fb−1 of pp collision data collected by the ATLAS experiment at √s=7 TeV and √s=8 TeV. The Standard Model (SM) Higgs boson hypothesis, corresponding to the quantum numbers JP=0+, is tested against several alternative spin scenarios, including non-SM spin-0 and spin-2 models with universal and non-universal couplings to fermions and vector bosons. All tested alternative models are excluded in favour of the SM Higgs boson hypothesis at more than 99.9 % confidence level. Using the H → ZZ∗ → 4ℓ and H → WW∗ → eνμν decays, the tensor structure of the interaction between the spin-0 boson and the SM vector bosons is also investigated. The observed distributions of variables sensitive to the non-SM tensor couplings are compatible with the SM predictions and constraints on the non-SM couplings are derived

Measurement of single top-quark production in association with a W boson in the single-lepton channel at \sqrt{s} = 8\,\text {TeV} with the ATLAS detector

The production cross-section of a top quark in association with a W boson is measured using proton–proton collisions at \sqrt{s} = 8\,\text {TeV}. The dataset corresponds to an integrated luminosity of 20.2\,\text {fb}^{-1}, and was collected in 2012 by the ATLAS detector at the Large Hadron Collider at CERN. The analysis is performed in the single-lepton channel. Events are selected by requiring one isolated lepton (electron or muon) and at least three jets. A neural network is trained to separate the tW signal from the dominant t{\bar{t}} background. The cross-section is extracted from a binned profile maximum-likelihood fit to a two-dimensional discriminant built from the neural-network output and the invariant mass of the hadronically decaying W boson. The measured cross-section is \sigma _{tW} = 26 \pm 7\,\text {pb}, in good agreement with the Standard Model expectation

Search for long-lived, massive particles in events with a displaced vertex and a muon with large impact parameter in pp collisions at root s=13 TeV with the ATLAS detector

A search for long-lived particles decaying into hadrons and at least one muon is presented. The analysis selects events that pass a muon or missing-transverse-momentum trigger and contain a displaced muon track and a displaced vertex. The analyzed dataset of proton-proton collisions at √ s = 13 TeV was collected with the ATLAS detector and corresponds to 136 fb − 1. The search employs dedicated reconstruction techniques that significantly increase the sensitivity to long-lived particle decays that occur in the ATLAS inner detector. Background estimates for Standard Model processes and instrumental effects are extracted from data. The observed event yields are compatible with those expected from background processes. The results are presented as limits at 95% confidence level on model-independent cross sections for processes beyond the Standard Model, and interpreted as exclusion limits in scenarios with pair production of long-lived top squarks that decay via a small R -parity-violating coupling into a quark and a muon. Top squarks with masses up to 1.7 TeV are excluded for a lifetime of 0.1 ns, and masses below 1.3 TeV are excluded for lifetimes between 0.01 ns and 30 ns

Search for long-lived neutral particles produced in pp collisions at √s = 13 TeV decaying into displaced hadronic jets in the ATLAS inner detector and muon spectrometer

A search is presented for pair production of long-lived neutral particles using 33     fb − 1 of √ s = 13     TeV proton–proton collision data, collected during 2016 by the ATLAS detector at the LHC. This search focuses on a topology in which one long-lived particle decays in the ATLAS inner detector and the other decays in the muon spectrometer. Special techniques are employed to reconstruct the displaced tracks and vertices in the inner detector and in the muon spectrometer. One event is observed that passes the full event selection, which is consistent with the estimated background. Limits are placed on scalar boson propagators with masses from 125 GeV to 1000 GeV decaying into pairs of long-lived hidden-sector scalars with masses from 8 GeV to 400 GeV. The limits placed on several low-mass scalars extend previous exclusion limits in the range of proper lifetimes c τ from 5 cm to 1 m

Measurement of the transverse momentum distribution of Drell–Yan lepton pairs in proton–proton collisions at s = 13 TeV with the ATLAS detector

Abstract: This paper describes precision measurements of the transverse momentum pTℓℓ (ℓ=e, μ) and of the angular variable ϕη∗ distributions of Drell–Yan lepton pairs in a mass range of 66–116 GeV. The analysis uses data from 36.1 fb-1 of proton–proton collisions at a centre-of-mass energy of s=13TeV collected by the ATLAS experiment at the LHC in 2015 and 2016. Measurements in electron-pair and muon-pair final states are performed in the same fiducial volumes, corrected for detector effects, and combined. Compared to previous measurements in proton–proton collisions at s=7 and 8TeV, these new measurements probe perturbative QCD at a higher centre-of-mass energy with a different composition of initial states. They reach a precision of 0.2% for the normalized spectra at low values of pTℓℓ. The data are compared with different QCD predictions, where it is found that predictions based on resummation approaches can describe the full spectrum within uncertainties

Search for new phenomena in final states with large jet multiplicities and missing transverse momentum using s = 13 TeV proton-proton collisions recorded by ATLAS in Run 2 of the LHC

Abstract: Results of a search for new particles decaying into eight or more jets and moderate missing transverse momentum are presented. The analysis uses 139 fb−1 of proton-proton collision data at s = 13 TeV collected by the ATLAS experiment at the Large Hadron Collider between 2015 and 2018. The selection rejects events containing isolated electrons or muons, and makes requirements according to the number of b-tagged jets and the scalar sum of masses of large-radius jets. The search extends previous analyses both in using a larger dataset and by employing improved jet and missing transverse momentum reconstruction methods which more cleanly separate signal from background processes. No evidence for physics beyond the Standard Model is found. The results are interpreted in the context of supersymmetry-inspired simplified models, significantly extending the limits on the gluino mass in those models. In particular, limits on the gluino mass are set at 2 TeV when the lightest neutralino is nearly massless in a model assuming a two-step cascade decay via the lightest chargino and second-lightest neutralino