A Heterogeneous In Vitro Three Dimensional Model of Tumour-Stroma Interactions Regulating Sprouting Angiogenesis

Angiogenesis, the formation of new blood vessels, is an essential process for tumour progression and is an area of significant therapeutic interest. Different in vitro systems and more complex in vivo systems have been described for the study of tumour angiogenesis. However, there are few human 3D in vitro systems described to date which mimic the cellular heterogeneity and complexity of angiogenesis within the tumour microenvironment. In this study we describe the Minitumour model – a 3 dimensional human spheroid-based system consisting of endothelial cells and fibroblasts in co-culture with the breast cancer cell line MDA-MB-231, for the study of tumour angiogenesis in vitro. After implantation in collagen-I gels, Minitumour spheroids form quantifiable endothelial capillary-like structures. The endothelial cell pre-capillary sprouts are supported by the fibroblasts, which act as mural cells, and their growth is increased by the presence of cancer cells. Characterisation of the Minitumour model using small molecule inhibitors and inhibitory antibodies show that endothelial sprout formation is dependent on growth factors and cytokines known to be important for tumour angiogenesis. The model also shows a response to anti-angiogenic agents similar to previously described in vivo data. We demonstrate that independent manipulation of the different cell types is possible, using common molecular techniques, before incorporation into the model. This aspect of Minitumour spheroid analysis makes this model ideal for high content studies of gene function in individual cell types, allowing for the dissection of their roles in cell-cell interactions. Finally, using this technique, we were able to show the requirement of the metalloproteinase MT1-MMP in endothelial cells and fibroblasts, but not cancer cells, for sprouting angiogenesis

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 fiducial cross-sections for t\bart production with one or two additional b-jets in pp collisions at √s =8 TeVusing the ATLAS detector

Fiducial cross-sections for $t\bar{t}$ production with one or two additional $b$-jets are reported, using an integrated luminosity of 20.3 fb$^{-1}$ of proton--proton collisions at a centre-of-mass energy of 8 TeV at the Large Hadron Collider, collected with the ATLAS detector. The cross-section times branching ratio for $t\bar{t}$ events with at least one additional $b$-jet is measured to be 950 $\pm$ 70 (stat.) $^{+240}_{-190}$ (syst.) fb in the lepton-plus-jets channel and 50 $\pm$ 10 (stat.) $^{+15}_{-10}$ (syst.) fb in the $e \mu$ channel. The cross-section times branching ratio for events with at least two additional $b$-jets is measured to be 19.3 $\pm$ 3.5 (stat.) $\pm$ 5.7 (syst.) fb in the dilepton channel ($e \mu$,\,$\mu\mu$, and \,$ee$) using a method based on tight selection criteria, and 13.5 $\pm$ 3.3 (stat.) $\pm$ 3.6 (syst.) fb using a looser selection that allows the background normalisation to be extracted from data. The latter method also measures a value of 1.30 $\pm$ 0.33 (stat.) $\pm$ 0.28 (syst.)\% for the ratio of $t\bar{t}$ production with two additional $b$-jets to $t\bar{t}$ production with any two additional jets. All measurements are in good agreement with recent theory predictions.Comment: 41 pages plus author list + cover page (58 total), 9 Figures, 16 tables, submitted to EPJC, all figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/TOPQ-2014-10

Search for W′→tb→qqbb decays in pp collisions at √s=8 TeV with the ATLAS detector

A search for a massive W′ gauge boson decaying to a top quark and a bottom quark is performed with the ATLAS detector in pp collisions at the LHC. The dataset was taken at a centre-of-mass energy of √s=8 TeV and corresponds to 20.3 fb−1 of integrated luminosity. This analysis is done in the hadronic decay mode of the top quark, where novel jet substructure techniques are used to identify jets from high-momentum top quarks. This allows for a search for high-mass W′ bosons in the range 1.5–3.0 TeV. b-tagging is used to identify jets originating from b-quarks. The data are consistent with Standard Model background-only expectations, and upper limits at 95 % confidence level are set on the W′→tb cross section times branching ratio ranging from 0.16pb to 0.33pb for left-handed W′ bosons, and ranging from 0.10pb to 0.21pb for W′ bosons with purely right-handed couplings. Upper limits at 95 % confidence level are set on the W′-boson coupling to tb as a function of the W′ mass using an effective field theory approach, which is independent of details of particular models predicting a W′boson

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

Measurement of the energy asymmetry in t(t)over-barj production at 13 TeV with the ATLAS experiment and interpretation in the SMEFT framework

A measurement of the energy asymmetry in jet-associated top-quark pair production is presented using $$139\,{\mathrm {fb}}^{-1}$$ 139 fb - 1 of data collected by the ATLAS detector at the Large Hadron Collider during pp collisions at $$\sqrt{s}=13\,\text {TeV}$$ s = 13 TeV . The observable measures the different probability of top and antitop quarks to have the higher energy as a function of the jet scattering angle with respect to the beam axis. The energy asymmetry is measured in the semileptonic $$t{\bar{t}}$$ t t ¯ decay channel, and the hadronically decaying top quark must have transverse momentum above $$350\,\text {GeV}$$ 350 GeV . The results are corrected for detector effects to particle level in three bins of the scattering angle of the associated jet. The measurement agrees with the SM prediction at next-to-leading-order accuracy in quantum chromodynamics in all three bins. In the bin with the largest expected asymmetry, where the jet is emitted perpendicular to the beam, the energy asymmetry is measured to be $$-0.043\pm 0.020$$ - 0.043 ± 0.020 , in agreement with the SM prediction of $$-0.037\pm 0.003$$ - 0.037 ± 0.003 . Interpreting this result in the framework of the Standard Model effective field theory (SMEFT), it is shown that the energy asymmetry is sensitive to the top-quark chirality in four-quark operators and is therefore a valuable new observable in global SMEFT fits

Search for chargino–neutralino pair production in final states with three leptons and missing transverse momentum in s√=13 TeV pp collisions with the ATLAS detector

A search for chargino–neutralino pair production in three-lepton final states with missing transverse momentum is presented. The study is based on a dataset of s√=13 TeV pp collisions recorded with the ATLAS detector at the LHC, corresponding to an integrated luminosity of 139 fb−1. No significant excess relative to the Standard Model predictions is found in data. The results are interpreted in simplified models of supersymmetry, and statistically combined with results from a previous ATLAS search for compressed spectra in two-lepton final states. Various scenarios for the production and decay of charginos (χ~±1) and neutralinos (χ~02) are considered. For pure higgsino χ~±1χ~02 pair-production scenarios, exclusion limits at 95% confidence level are set on χ~02 masses up to 210 GeV. Limits are also set for pure wino χ~±1χ~02 pair production, on χ~02 masses up to 640 GeV for decays via on-shell W and Z bosons, up to 300 GeV for decays via off-shell W and Z bosons, and up to 190 GeV for decays via W and Standard Model Higgs bosons

Identification and rejection of pile-up jets at high pseudorapidity with the ATLAS detector

The rejection of forward jets originating from additional proton–proton interactions (pile-up) is crucial for a variety of physics analyses at the LHC, including Standard Model measurements and searches for physics beyond the Standard Model. The identification of such jets is challenging due to the lack of track and vertex information in the pseudorapidity range |η| > 2.5. This paper presents a novel strategy for forward pile-up jet tagging that exploits jet shapes and topological jet correlations in pile-up interactions. Measurements of the per-jet tagging efficiency are presented using a data set of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of 13 TeV collected with the ATLAS detector. The fraction of pile-up jets rejected in the range 2.5 < |η| < 4.5 is estimated in simulated events with an average of 22 interactions per bunch-crossing. It increases with jet transverse momentum and, for jets with transverse momentum between 20 and 50 GeV, it ranges between 49% and 67% with an efficiency of 85% for selecting hard-scatter jets. A case study is performed in Higgs boson production via the vector-boson fusion process, showing that these techniques mitigate the background growth due to additional proton–proton interactions, thus enhancing the reach for such signatures

Search for W′→tb→qqbbW' \rightarrow tb \rightarrow qqbb W ′ → t b → q q b b decays in pppp p p collisions at s\sqrt{s} s = 8 TeV with the ATLAS detector

A search for a massive W′ gauge boson decaying to a top quark and a bottom quark is performed with the ATLAS detector in pp collisions at the LHC. The dataset was taken at a centre-of-mass energy of s√=8 TeVs=8 TeV and corresponds to 20.3 fb −120.3 fb −1 of integrated luminosity. This analysis is done in the hadronic decay mode of the top quark, where novel jet substructure techniques are used to identify jets from high-momentum top quarks. This allows for a search for high-mass W′ bosons in the range 1.5–3.0 TeV TeV. bb-tagging is used to identify jets originating from bb-quarks. The data are consistent with Standard Model background-only expectations, and upper limits at 95 % confidence level are set on the W′→tbW′→tb cross section times branching ratio ranging from 0.16pb0.16pb to 0.33pb0.33pb for left-handed W′W′ bosons, and ranging from 0.10pb0.10pb to 0.21pb0.21pb for W′ bosons with purely right-handed couplings. Upper limits at 95 % confidence level are set on the W′-boson coupling to tb as a function of the W′ mass using an effective field theory approach, which is independent of details of particular models predicting a W′ boson