Multiple lines of evidence suggest that Toll-like receptors (TLRs) are dysregulated and emerging evidence suggests that many endogenous ligands are also elevated in the disease leading to 'sterile inflammation' and ultimately the induction of fibrosis. Currently, no effective therapy exists and exploiting the innate immune system perturbation may be one possible avenue. Innate immune dysregulation is key in SSc pathogenesis and may represent a novel target.

The ATLAS experiment at the Large Hadron Collider has a broad physics programme ranging from precision measurements to direct searches for new particles and new interactions, requiring ever larger and ever more accurate datasets of simulated Monte Carlo events. Detector simulation with Geant4 is accurate but requires significant CPU resources. Over the past decade, ATLAS has developed and utilized tools that replace the most CPU-intensive component of the simulation—the calorimeter shower simulation—with faster simulation methods. Here, AtlFast3, the next generation of high-accuracy fast simulation in ATLAS, is introduced. AtlFast3 combines parameterized approaches with machine-learning techniques and is deployed to meet current and future computing challenges, and simulation needs of the ATLAS experiment. With highly accurate performance and significantly improved modelling of substructure within jets, AtlFast3 can simulate large numbers of events for a wide range of physics processes.

This paper presents an analysis at next-to-next-to-leading order in the theory of quantum chromodynamics for the determination of a new set of proton parton distribution functions using diverse measurements in pp collisions at $$\sqrt{s} = 7$$ s = 7 , 8 and 13 TeV, performed by the ATLAS experiment at the Large Hadron Collider, together with deep inelastic scattering data from ep collisions at the HERA collider. The ATLAS data sets considered are differential cross-section measurements of inclusive $$W^{\pm }$$ W ± and $$Z/\gamma ^*$$ Z / γ ∗ boson production, $$W^{\pm }$$ W ± and Z boson production in association with jets, $$t\bar{t}$$ t t ¯ production, inclusive jet production and direct photon production. In the analysis, particular attention is paid to the correlation of systematic uncertainties within and between the various ATLAS data sets and to the impact of model, theoretical and parameterisation uncertainties. The resulting set of parton distribution functions is called ATLASpdf21.

A search for the Higgs boson decaying into a pair of charm quarks is presented. The analysis uses proton–proton collisions to target the production of a Higgs boson in association with a leptonically decaying W or Z boson. The dataset delivered by the LHC at a centre-of-mass energy of "Equation missing" and recorded by the ATLAS detector corresponds to an integrated luminosity of 139 $$\text{ fb}^{-1}$$ fb - 1 . Flavour-tagging algorithms are used to identify jets originating from the hadronisation of charm quarks. The analysis method is validated with the simultaneous measurement of WW, WZ and ZZ production, with observed (expected) significances of 2.6 (2.2) standard deviations above the background-only prediction for the $$(W/Z)Z(\rightarrow c{\bar{c}})$$ ( W / Z ) Z ( → c c ¯ ) process and 3.8 (4.6) standard deviations for the $$(W/Z)W(\rightarrow cq)$$ ( W / Z ) W ( → c q ) process. The $$(W/Z)H(\rightarrow c {\bar{c}})$$ ( W / Z ) H ( → c c ¯ ) search yields an observed (expected) upper limit of 26 (31) times the predicted Standard Model cross-section times branching fraction for a Higgs boson with a mass of "Equation missing", corresponding to an observed (expected) constraint on the charm Yukawa coupling modifier $$|\kappa _c| < 8.5~(12.4)$$ | κ c | < 8.5 ( 12.4 ) , at the 95% confidence level. A combination with the ATLAS $$(W/Z)H, H\rightarrow b{\bar{b}}$$ ( W / Z ) H , H → b b ¯ analysis is performed, allowing the ratio $$\kappa _c / \kappa _b$$ κ c / κ b to be constrained to less than 4.5 at the 95% confidence level, smaller than the ratio of the b- and c-quark masses, and therefore determines the Higgs-charm coupling to be weaker than the Higgs-bottom coupling at the 95% confidence level.

A direct search for Higgs bosons produced via vector-boson fusion and subsequently decaying into invisible particles is reported. The analysis uses 139 fb−1 of pp collision data at a centre-of-mass energy of $$ \sqrt{s} $$ s = 13 TeV recorded by the ATLAS detector at the LHC. The observed numbers of events are found to be in agreement with the background expectation from Standard Model processes. For a scalar Higgs boson with a mass of 125 GeV and a Standard Model production cross section, an observed upper limit of 0.145 is placed on the branching fraction of its decay into invisible particles at 95% confidence level, with an expected limit of 0.103. These results are interpreted in the context of models where the Higgs boson acts as a portal to dark matter, and limits are set on the scattering cross section of weakly interacting massive particles and nucleons. Invisible decays of additional scalar bosons with masses from 50 GeV to 2 TeV are also studied, and the derived upper limits on the cross section times branching fraction decrease with increasing mass from 1.0 pb for a scalar boson mass of 50 GeV to 0.1 pb at a mass of 2 TeV.