Atherosclerotic plaque development in mice is enhanced by myeloid ZEB1 downregulation.

Accumulation of lipid-laden macrophages within the arterial neointima is a critical step in atherosclerotic plaque formation. Here, we show that reduced levels of the cellular plasticity factor ZEB1 in macrophages increase atherosclerotic plaque formation and the chance of cardiovascular events. Compared to control counterparts (Zeb1WT/ApoeKO), male mice with Zeb1 ablation in their myeloid cells (Zeb1∆M/ApoeKO) have larger atherosclerotic plaques and higher lipid accumulation in their macrophages due to delayed lipid traffic and deficient cholesterol efflux. Zeb1∆M/ApoeKO mice display more pronounced systemic metabolic alterations than Zeb1WT/ApoeKO mice, with higher serum levels of low-density lipoproteins and inflammatory cytokines and larger ectopic fat deposits. Higher lipid accumulation in Zeb1∆M macrophages is reverted by the exogenous expression of Zeb1 through macrophage-targeted nanoparticles. In vivo administration of these nanoparticles reduces atherosclerotic plaque formation in Zeb1∆M/ApoeKO mice. Finally, low ZEB1 expression in human endarterectomies is associated with plaque rupture and cardiovascular events. These results set ZEB1 in macrophages as a potential target in the treatment of atherosclerosis.S

Search for direct top squark pair production in events with a Z boson, b-jets and missing transverse momentum in s √ = 8 TeV pp collisions with the ATLAS detector

A search is presented for direct top squark pair production using events with at least two leptons including a same-flavour opposite-sign pair with invariant mass consistent with the Z boson mass, jets tagged as originating from b-quarks and missing transverse momentum. The analysis is performed with proton–proton collision data at s√=8 TeV collected with the ATLAS detector at the LHC in 2012 corresponding to an integrated luminosity of 20.3 fb−¹. No excess beyond the Standard Model expectation is observed. Interpretations of the results are provided in models based on the direct pair production of the heavier top squark state (t~2) followed by the decay to the lighter top squark state (t~1) via t~2→Zt~1, and for t~1 pair production in natural gauge-mediated supersymmetry breaking scenarios where the neutralino (χ~10) is the next-to-lightest supersymmetric particle and decays producing a Z boson and a gravitino (G~) via the χ~10→ZG~ process

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Standard Model Physics at the HL-LHC and HE-LHC

The successful operation of the Large Hadron Collider (LHC) and the excellent performance of the ATLAS, CMS, LHCb and ALICE detectors in Run-1 and Run-2 with $pp$ collisions at center-of-mass energies of 7, 8 and 13 TeV as well as the giant leap in precision calculations and modeling of fundamental interactions at hadron colliders have allowed an extraordinary breadth of physics studies including precision measurements of a variety physics processes. The LHC results have so far confirmed the validity of the Standard Model of particle physics up to unprecedented energy scales and with great precision in the sectors of strong and electroweak interactions as well as flavour physics, for instance in top quark physics. The upgrade of the LHC to a High Luminosity phase (HL-LHC) at 14 TeV center-of-mass energy with 3 ab$^{-1}$ of integrated luminosity will probe the Standard Model with even greater precision and will extend the sensitivity to possible anomalies in the Standard Model, thanks to a ten-fold larger data set, upgraded detectors and expected improvements in the theoretical understanding. This document summarises the physics reach of the HL-LHC in the realm of strong and electroweak interactions and top quark physics, and provides a glimpse of the potential of a possible further upgrade of the LHC to a 27 TeV $pp$ collider, the High-Energy LHC (HE-LHC), assumed to accumulate an integrated luminosity of 15 ab$^{-1}$

Search for pair and single production of new heavy quarks that decay to a Z boson and a third-generation quark in pp collisions at root s=8 TeV with the ATLAS detector

Open Access. This article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited

Search for new phenomena in events with three or more charged leptons in pppp collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

A generic search for anomalous production of events with at least three charged leptons is presented. The data sample consists of $pp$ collisions at $\sqrt{s}=8$ TeV collected in 2012 by the ATLAS experiment at the CERN Large Hadron Collider, and corresponds to an integrated luminosity of 20.3 fb$^{-1}$. Events are required to have at least three selected lepton candidates, at least two of which must be electrons or muons, while the third may be a hadronically decaying tau. Selected events are categorized based on their lepton flavour content and signal regions are constructed using several kinematic variables of interest. No significant deviations from Standard Model predictions are observed. Model-independent upper limits on contributions from beyond the Standard Model phenomena are provided for each signal region, along with prescription to re-interpret the limits for any model. Constraints are also placed on models predicting doubly charged Higgs bosons and excited leptons. For doubly charged Higgs bosons decaying to $e\tau$ or $\mu\tau$, lower limits on the mass are set at 400 GeV at 95% confidence level. For excited leptons, constraints are provided as functions of both the mass of the excited state and the compositeness scale $\Lambda$, with the strongest mass constraints arising in regions where the mass equals $\Lambda$. In such scenarios, lower mass limits are set at 3.0 TeV for excited electrons and muons, 2.5 TeV for excited taus, and 1.6 TeV for every excited-neutrino flavour.Comment: 442 pages plus author list + cover pages (60 pages total), 6 figures, 25 tables, submitted to JHEP, All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/EXOT-2012-20

Inflammatory macrophages reprogram to immunosuppression by reducing mitochondrial translation

Acknowledgements: We are grateful to Dr. F. Sanchez-Madrid (Hospital Princesa and CNIC, Madrid, Spain), Dr. D. Cebrian (CNIC, Madrid, Spain), and Dr. A. Valledor (University of Barcelona, Spain) for helpful insights on early versions of the manuscript. We thank Dr. C. Stephan-Otto Attolini (BIST-IRB, Barcelona, Spain) and Dr. J. Rios (IDIBAPS, Hospital Clinic, and Autonomous University of Barcelona, Barcelona, Spain) for their expert guidance on the statistical analyses of the data in the study. We also thank Dr. L. Ribas de Pouplana (BIST-IRB, Barcelona, Spain) for advice on mitochondrial translation experiments. We acknowledge technical assistance by staff in the Flow Cytometry Unit at IDIBAPS, the Molecular Interactions Services Unit at the Biomedical Research Institute of Bellvitge (IDIBELL), and the Transmission Electron Microscopy Unit at the University of Barcelona School of Medicine. We also thank A Téllez (Hospital Clinic, Barcelona, Spain) for his help in collecting samples from septic patients, and Dr. MJ Fernández-Aceñero (Hospital Clinico San Carlos, Madrid, Spain) for help in collecting skin samples from healthy controls, psoriatic patients, and melanoma patients. We are also thankful to Dr. DC Dean (University of Louisville, KY, USA) for his generous gift of an anti-ZEB1 polyclonal antibody. We thank Dr. A. Garcia for the artistic drawing of schematics in the article. IDIBAPS is partly funded by the CERCA Programme of Generalitat de Catalunya. The study was conducted at IDIBAPS’ Centre de Recerca Biomèdica Cellex building, which was partly funded by the Cellex Foundation. The different parts of this study were independently funded by grants to AP from the Leo Foundation (LF-OC-19-000166), the Catalan Agency for Management of University and Research Grants (AGAUR) (2017-SGR-1174 and 2021-SGR-01328), and the Spanish State Research Agency (AEI) of the Ministry of Science and Innovation (MICINN) (PID2020-116338RB-I00) as part of MICINN’s National Scientific and Technical Research and Innovation 2021-2023 Plan, which is co-financed by the European Regional Development Fund (ERDF) of the European Union Commission. AB is a recipient of a PhD scholarship from AGAUR (FI Program, 2021 FI_B 00514).Funder: Government of Catalonia | Agència de Gestió d'Ajuts Universitaris i de Recerca (Agency for Management of University and Research Grants)Acute inflammation can either resolve through immunosuppression or persist, leading to chronic inflammation. These transitions are driven by distinct molecular and metabolic reprogramming of immune cells. The anti-diabetic drug Metformin inhibits acute and chronic inflammation through mechanisms still not fully understood. Here, we report that the anti-inflammatory and reactive-oxygen-species-inhibiting effects of Metformin depend on the expression of the plasticity factor ZEB1 in macrophages. Using mice lacking Zeb1 in their myeloid cells and human patient samples, we show that ZEB1 plays a dual role, being essential in both initiating and resolving inflammation by inducing macrophages to transition into an immunosuppressed state. ZEB1 mediates these diverging effects in inflammation and immunosuppression by modulating mitochondrial content through activation of autophagy and inhibition of mitochondrial protein translation. During the transition from inflammation to immunosuppression, Metformin mimics the metabolic reprogramming of myeloid cells induced by ZEB1. Mechanistically, in immunosuppression, ZEB1 inhibits amino acid uptake, leading to downregulation of mTORC1 signalling and a decrease in mitochondrial translation in macrophages. These results identify ZEB1 as a driver of myeloid cell metabolic plasticity, suggesting that targeting its expression and function could serve as a strategy to modulate dysregulated inflammation and immunosuppression

Handbook of LHC Higgs Cross Sections: 4. Deciphering the Nature of the Higgs Sector

868 pages, 295 figures, 248 tables and 1642 citations. Working Group web page: https://twiki.cern.ch/twiki/bin/view/LHCPhysics/LHCHXSWGThis Report summarizes the results of the activities of the LHC Higgs Cross Section Working Group in the period 2014-2016. The main goal of the working group was to present the state-of-the-art of Higgs physics at the LHC, integrating all new results that have appeared in the last few years. The first part compiles the most up-to-date predictions of Higgs boson production cross sections and decay branching ratios, parton distribution functions, and off-shell Higgs boson production and interference effects. The second part discusses the recent progress in Higgs effective field theory predictions, followed by the third part on pseudo-observables, simplified template cross section and fiducial cross section measurements, which give the baseline framework for Higgs boson property measurements. The fourth part deals with the beyond the Standard Model predictions of various benchmark scenarios of Minimal Supersymmetric Standard Model, extended scalar sector, Next-to-Minimal Supersymmetric Standard Model and exotic Higgs boson decays. This report follows three previous working-group reports: Handbook of LHC Higgs Cross Sections: 1. Inclusive Observables (CERN-2011-002), Handbook of LHC Higgs Cross Sections: 2. Differential Distributions (CERN-2012-002), and Handbook of LHC Higgs Cross Sections: 3. Higgs properties (CERN-2013-004). The current report serves as the baseline reference for Higgs physics in LHC Run 2 and beyond

Handbook of LHC Higgs Cross Sections: 4. Deciphering the Nature of the Higgs Sector

868 pages, 295 figures, 248 tables and 1642 citations. Working Group web page: https://twiki.cern.ch/twiki/bin/view/LHCPhysics/LHCHXSWGThis Report summarizes the results of the activities of the LHC Higgs Cross Section Working Group in the period 2014-2016. The main goal of the working group was to present the state-of-the-art of Higgs physics at the LHC, integrating all new results that have appeared in the last few years. The first part compiles the most up-to-date predictions of Higgs boson production cross sections and decay branching ratios, parton distribution functions, and off-shell Higgs boson production and interference effects. The second part discusses the recent progress in Higgs effective field theory predictions, followed by the third part on pseudo-observables, simplified template cross section and fiducial cross section measurements, which give the baseline framework for Higgs boson property measurements. The fourth part deals with the beyond the Standard Model predictions of various benchmark scenarios of Minimal Supersymmetric Standard Model, extended scalar sector, Next-to-Minimal Supersymmetric Standard Model and exotic Higgs boson decays. This report follows three previous working-group reports: Handbook of LHC Higgs Cross Sections: 1. Inclusive Observables (CERN-2011-002), Handbook of LHC Higgs Cross Sections: 2. Differential Distributions (CERN-2012-002), and Handbook of LHC Higgs Cross Sections: 3. Higgs properties (CERN-2013-004). The current report serves as the baseline reference for Higgs physics in LHC Run 2 and beyond