Tumor-Induced Cholesterol Efflux from Macrophages Drives IL-4 Mediated Reprogramming and Tumor Progression

Tumor-associated macrophages (TAM) have been shown to have important roles in the malignant progression of various cancers. However, macrophages also posses intrinsic tumoricidal activity and can promote the activity of cytotoxic lymphocytes, but they rapidly adopt an alternative phenotype within tumors, associated with immune-suppression and trophic functions that support tumor growth. The mechanisms that promote TAM polarization in the tumor-microenvironment remain poorly understood, these mechanisms may represent important therapeutic targets to block the tumor-promoting functions of TAM and restore their anti-tumor potential. Here we have characterized TAM in a mouse model of metastatic ovarian cancer. We show that ovarian cancer cells promote membrane-cholesterol efflux and the depletion of lipid rafts from macrophages. Increased cholesterol efflux promoted IL-4 mediated reprogramming while inhibiting IFNγ-induced gene expression. These studies reveal an unexpected role for tumor-induced membrane-cholesterol efflux in driving the IL-4 signaling and the tumor-promoting functions of TAM, while rendering them refractory to pro-inflammatory stimuli. Thus, preventing cholesterol efflux in TAM could represent a novel therapeutic strategy to block pro-tumor functions and restore anti-tumor immunity. Biopharmaceutic

BioModels—15 years of sharing computational models in life science

Computational modelling has become increasingly common in life science research. To provide a platform to support universal sharing, easy accessibility and model reproducibility, BioModels (https://www.ebi.ac.uk/biomodels/), a repository for mathematical models, was established in 2005. The current BioModels platform allows submission of models encoded in diverse modelling formats, including SBML, CellML, PharmML, COMBINE archive, MATLAB, Mathematica, R, Python or C++. The models submitted to BioModels are curated to verify the computational representation of the biological process and the reproducibility of the simulation results in the reference publication. The curation also involves encoding models in standard formats and annotation with controlled vocabularies following MIRIAM (minimal information required in the annotation of biochemical models) guidelines. BioModels now accepts large-scale submission of auto-generated computational models. With gradual growth in content over 15 years, BioModels currently hosts about 2000 models from the published literature. With about 800 curated models, BioModels has become the world’s largest repository of curated models and emerged as the third most used data resource after PubMed and Google Scholar among the scientists who use modelling in their research. Thus, BioModels benefits modellers by providing access to reliable and semantically enriched curated models in standard formats that are easy to share, reproduce and reuse

Constraints on Higgs boson properties using WW∗(→ eνμν) jj production in 36.1fb-1 of √s=13 TeV pp collisions with the ATLAS detector

This article presents the results of two studies of Higgs boson properties using the WW∗(→ eνμν) jj final state, based on a dataset corresponding to 36.1 fb - 1 of s=13 TeV proton–proton collisions recorded by the ATLAS experiment at the Large Hadron Collider. The first study targets Higgs boson production via gluon–gluon fusion and constrains the CP properties of the effective Higgs–gluon interaction. Using angular distributions and the overall rate, a value of tan (α) = 0.0 ± 0.4 (stat.) ± 0.3 (syst.) is obtained for the tangent of the mixing angle for CP-even and CP-odd contributions. The second study exploits the vector-boson fusion production mechanism to probe the Higgs boson couplings to longitudinally and transversely polarised W and Z bosons in both the production and the decay of the Higgs boson; these couplings have not been directly constrained previously. The polarisation-dependent coupling-strength scale factors are defined as the ratios of the measured polarisation-dependent coupling strengths to those predicted by the Standard Model, and are determined using rate and kinematic information to be aL=0.91-0.18+0.10(stat.)-0.17+0.09(syst.) and aT= 1.2 ± 0.4 (stat.)-0.3+0.2(syst.). These coupling strengths are translated into pseudo-observables, resulting in κVV=0.91-0.18+0.10(stat.)-0.17+0.09(syst.) and ϵVV=0.13-0.20+0.28 (stat.)-0.10+0.08(syst.). All results are consistent with the Standard Model predictions

A search for the dimuon decay of the Standard Model Higgs boson with the ATLAS detector

A search for the dimuon decay of the Standard Model (SM) Higgs boson is performed using data corresponding to an integrated luminosity of 139 fb(-1) collected with the ATLAS detector in Run 2 pp collisions at root s = 13 TeV at the Large Hadron Collider. The observed (expected) significance over the background-only hypothesis for a Higgs boson with a mass of 125.09 GeV is 2.0 sigma (1.7 sigma). The observed upper limit on the cross section times branching ratio for pp -> H -> mu mu is 2.2 times the SM prediction at 95% confidence level, while the expected limit on a H -> mu mu signal assuming the absence (presence) of a SM signal is 1.1(2.0). The best-fit value of the signal strength parameter, defined as the ratio of the observed signal yield to the one expected in the SM, is mu = 1.2 +/- 0.6. (C) 2020 The Author(s). Published by Elsevier B.V

The ATLAS fast tracKer system

The ATLAS Fast TracKer (FTK) was designed to provide full tracking for the ATLAS high-level trigger by using pattern recognition based on Associative Memory (AM) chips and fitting in high-speed field programmable gate arrays. The tracks found by the FTK are based on inputs from all modules of the pixel and silicon microstrip trackers. The as-built FTK system and components are described, as is the online software used to control them while running in the ATLAS data acquisition system. Also described is the simulation of the FTK hardware and the optimization of the AM pattern banks. An optimization for long-lived particles with large impact parameter values is included. A test of the FTK system with the data playback facility that allowed the FTK to be commissioned during the shutdown between Run 2 and Run 3 of the LHC is reported. The resulting tracks from part of the FTK system covering a limited η-ϕ region of the detector are compared with the output from the FTK simulation. It is shown that FTK performance is in good agreement with the simulation. © The ATLAS collaboratio

Alignment of the ATLAS Inner Detector in Run 2

The performance of the ATLAS Inner Detector alignment has been studied using pp collision data at v s = 13 TeV collected by the ATLAS experiment during Run 2 (2015-2018) of the Large Hadron Collider (LHC). The goal of the detector alignment is to determine the detector geometry as accurately as possible and correct for time-dependent movements. The Inner Detector alignment is based on the minimization of track-hit residuals in a sequence of hierarchical levels, from global mechanical assembly structures to local sensors. Subsequent levels have increasing numbers of degrees of freedom; in total there are almost 750,000. The alignment determines detector geometry on both short and long timescales, where short timescales describe movementswithin anLHCfill. The performance and possible track parameter biases originating from systematic detector deformations are evaluated. Momentum biases are studied using resonances decaying to muons or to electrons. The residual sagitta bias and momentum scale bias after alignment are reduced to less than similar to 0.1 TeV-1 and 0.9 x 10(-3), respectively. Impact parameter biases are also evaluated using tracks within jets

Measurements of jet observables sensitive to b-quark fragmentation in tt¯ events at the LHC with the ATLAS detector

Several observables sensitive to the fragmentation of b quarks into b hadrons are measured using 36 fb-1 of s=13 TeV proton-proton collision data collected with the ATLAS detector at the LHC. Jets containing b hadrons are obtained from a sample of dileptonic tt¯ events, and the associated set of charged-particle tracks is separated into those from the primary pp interaction vertex and those from the displaced b-decay secondary vertex. This division is used to construct observables that characterize the longitudinal and transverse momentum distributions of the b hadron within the jet. The measurements have been corrected for detector effects and provide a test of heavy-quark-fragmentation modeling at the LHC in a system where the top-quark decay products are color connected to the proton beam remnants. The unfolded distributions are compared with the predictions of several modern Monte Carlo parton-shower generators and generator tunes, and a wide range of agreement with the data is observed, with p values varying from 5×10-4 to 0.98. These measurements complement similar measurements from e+e- collider experiments in which the b quarks originate from a color singlet Z/γ∗

Search for resonances decaying into photon pairs in 139 fb−1 of pp collisions at root 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 root 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. (C) 2021 The Author(s). Published by Elsevier B.V