VEGF is upregulated by hypoxia-induced mitogenic factor via the PI-3K/Akt-NF-κB signaling pathway

BACKGROUND: Hypoxia-induced mitogenic factor (HIMF) is developmentally regulated and plays an important role in lung pathogenesis. We initially found that HIMF promotes vascular tubule formation in a matrigel plug model. In this study, we investigated the mechanisms which HIMF enhances expression of vascular endothelial growth factor (VEGF) in lung tissues and epithelial cells. METHODS: Recombinant HIMF protein was intratracheally instilled into adult mouse lungs, VEGF expression was examined by immunohistochemical staining and Western blot. The promoter-luciferase reporter assay, RT-PCR, and Western blot were performed to examine the effects of HIMF on VEGF expression in mouse lung epithelial cell line MLE-12. The activation of NF-kappa B (NF-κB) and phosphorylation of Akt, IKK and IκBα were examined by luciferase assay and Western blot, respectively. RESULTS: Intratracheal instillation of HIMF protein resulted in significant increase of VEGF, mainly localized to airway epithelial and alveolar type II cells. Deletion of NF-κB binding sites within VEGF promoter abolished HIMF-induced VEGF expression in MLE-12 cells, suggesting that activation of NF-κB is essential for VEGF upregulation induced by HIMF. Stimulation of lung epithelial cells by HIMF resulted in phosphorylation of IKK and IκBα, leading to activation of NF-κB. In addition, HIMF strongly induced Akt phosphorylation, and suppression of Akt activation by specific inhibitors and dominant negative mutants for PI-3K, and IKK or IκBα blocked HIMF-induced NF-κB activation and attenuated HIMF-induced VEGF production. CONCLUSION: These results suggest that HIMF enhances VEGF production in mouse lung epithelial cells in a PI-3K/Akt-NF-κB signaling pathway-dependent manner, and may play critical roles in pulmonary angiogenesis

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Knowledge-based matrix factorization temporally resolves the cellular responses to IL-6 stimulation

<p>Abstract</p> <p>Background</p> <p>External stimulations of cells by hormones, cytokines or growth factors activate signal transduction pathways that subsequently induce a re-arrangement of cellular gene expression. The analysis of such changes is complicated, as they consist of multi-layered temporal responses. While classical analyses based on clustering or gene set enrichment only partly reveal this information, matrix factorization techniques are well suited for a detailed temporal analysis. In signal processing, factorization techniques incorporating data properties like spatial and temporal correlation structure have shown to be robust and computationally efficient. However, such correlation-based methods have so far not be applied in bioinformatics, because large scale biological data rarely imply a natural order that allows the definition of a delayed correlation function.</p> <p>Results</p> <p>We therefore develop the concept of graph-decorrelation. We encode prior knowledge like transcriptional regulation, protein interactions or metabolic pathways in a weighted directed graph. By linking features along this underlying graph, we introduce a partial ordering of the features (e.g. genes) and are thus able to define a graph-delayed correlation function. Using this framework as constraint to the matrix factorization task allows us to set up the fast and robust graph-decorrelation algorithm (GraDe). To analyze alterations in the gene response in <it>IL-6 </it>stimulated primary mouse hepatocytes, we performed a time-course microarray experiment and applied GraDe. In contrast to standard techniques, the extracted time-resolved gene expression profiles showed that <it>IL-6 </it>activates genes involved in cell cycle progression and cell division. Genes linked to metabolic and apoptotic processes are down-regulated indicating that <it>IL-6 </it>mediated priming renders hepatocytes more responsive towards cell proliferation and reduces expenditures for the energy metabolism.</p> <p>Conclusions</p> <p>GraDe provides a novel framework for the decomposition of large-scale 'omics' data. We were able to show that including prior knowledge into the separation task leads to a much more structured and detailed separation of the time-dependent responses upon <it>IL-6 </it>stimulation compared to standard methods. A Matlab implementation of the GraDe algorithm is freely available at <url>http://cmb.helmholtz-muenchen.de/grade</url>.</p

Measurement of inclusive and differential cross sections in the H -> ZZ* -> 4l decay channel in pp collisions at root s=13 TeV with the ATLAS detector

Inclusive and differential fiducial cross sections of Higgs boson production in proton-proton collisions are measured in the H -> Z Z* -> 4l decay channel. The proton-proton collision data were produced at the Large Hadron Collider at a centre-of-mass energy of 13 TeV and recorded by the ATLAS detector in 2015 and 2016, corresponding to an integrated luminosity of 36.1 fb(-1). The inclusive fiducial cross section in the H -> Z Z* -> 4l decay channel is measured to be 3.62 +/- 0.50 (stat) (+0.25)(-0.20) (sys) fb, in agreement with the Standard Model prediction of 2.91 +/- 0.13 fb. The cross section is also extrapolated to the total phase space including all Standard Model Higgs boson decays. Several differential fiducial cross sections are measured for observables sensitive to the Higgs boson production and decay, including kinematic distributions of jets produced in association with the Higgs boson. Good agreement is found between data and Standard Model predictions. The results are used to put constraints on anomalous Higgs boson interactions with Standard Model particles, using the pseudo-observable extension to the kappa-framework

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 vertical bar eta vertical bar > 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 < vertical bar eta vertical bar < 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 the Dimuon Decay of the Higgs Boson in pp Collisions at √s=13 TeV with the ATLAS Detector

A search for the dimuon decay of the Higgs boson was performed using data corresponding to an integrated luminosity of 36.1 fb(-1) collected with the ATLAS detector in pp collisions at root s = 13 TeV at the Large Hadron Collider. No significant excess is observed above the expected background. The observed (expected) upper limit on the cross section times branching ratio is 3.0 (3.1) times the Standard Model prediction at the 95% confidence level for a Higgs boson mass of 125 GeV. When combined with the pp collision data at root s = 7 TeV and root s = 8 TeV, the observed (expected) upper limit is 2.8 (2.9) times the Standard Model prediction

Searches for the Z gamma decay mode of the Higgs boson and for new high-mass resonances in pp collisions at root s=13 TeV with the ATLAS detector

This article presents searches for the Z gamma decay of the Higgs boson and for narrow high-mass resonances decaying to Z gamma, exploiting Z boson decays to pairs of electrons or muons. The data analysis uses 36.1 fb(-1) of pp collisions at root s = 13 recorded by the ATLAS detector at the CERN Large Hadron Collider. The data are found to be consistent with the expected Standard Model background. The observed (expected - assuming Standard Model pp -> H -> Z gamma production and decay) upper limit on the production cross section times the branching ratio for pp -> H -> Z gamma is 6.6. (5.2) times the Standard Model prediction at the 95% confidence level for a Higgs boson mass of 125.09 GeV. In addition, upper limits are set on the production cross section times the branching ratio as a function of the mass of a narrow resonance between 250 GeV and 2.4 TeV, assuming spin-0 resonances produced via gluon-gluon fusion, and spin-2 resonances produced via gluon-gluon or quark-antiquark initial states. For high-mass spin-0 resonances, the observed (expected) limits vary between 88 fb (61 fb) and 2.8 fb (2.7 fb) for the mass range from 250 GeV to 2.4 TeV at the 95% confidence level

Measurement of jet fragmentation in Pb+Pb and pp collisions at sNN−−−√=2.76 TeV with the ATLAS detector at the LHC

The distributions of transverse momentum and longitudinal momentum fraction of charged particles in jets are measured in Pb+Pb and pp collisions with the ATLAS detector at the LHC. The distributions are measured as a function of jet transverse momentum and rapidity. The analysis utilises an integrated luminosity of 0.14 nb(-1) of Pb+Pb data and 4.0 pb(-1) of pp data collected in 2011 and 2013, respectively, at the same centre-of-mass energy of 2.76 TeV per colliding nucleon pair. The distributions measured in pp collisions are used as a reference for those measured in Pb+Pb collisions in order to evaluate the impact on the internal structure of jets from the jet energy loss of fast partons propagating through the hot, dense medium created in heavy-ion collisions. Modest but significant centrality-dependent modifications of fragmentation functions in Pb+Pb collisions with respect to those in pp collisions are seen. No significant dependence of modifications on jet p(T) and rapidity selections is observed except for the fragments with the highest transverse momenta for which some reduction of yields is observed for more forward jets