Influence of the nature of the sterol on the behavior of palmitic acid/sterol mixtures and their derived liposomes

AbstractThe phase behavior of mixtures formed with palmitic acid (PA) and one of the following sterols (dihydrocholesterol, ergosterol, 7-dehydrocholesterol, stigmasterol and stigmastanol), in a PA/sterol molar ratio of 3/7, has been characterized by IR and 2H NMR spectroscopy at different pH. Our study shows that it is possible to form liquid-ordered (lo) lamellar phases with these binary non-phospholipid mixtures. The characterization of alkyl chain dynamics of PA in these systems revealed the large ordering effect of the sterols. It was possible to extrude these systems, using standard extrusion techniques, to form large unilamellar vesicles (LUVs), except in the case of ergosterol-containing mixture. The resulting LUVs displayed a very limited passive permeability consistent with the high sterol concentration. In addition, the stability of these PA/sterol self-assembled bilayers was also found to be pH-sensitive, therefore, potentially useful as nanovectors. By examining different sterols, we could establish some correlations between the structure of these bilayers and their permeability properties. The structure of the side chain at C17 of the sterol appears to play a prime role in the mixing properties with fatty acid

Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7

Cancer Signaling networks and Molecular Therapeutic

Discovery of a highly active anticancer analogue of cardamonin that acts as an inducer of caspase-dependent apoptosis and modulator of the mTOR pathway

Nineteen analogues of cardamonin were semi-synthesized and tested against A549 and HK1 cell lines. The analogues were fully characterized via IR and NMR analyses, while compound 19 (a Cu (II) complex of cardamonin) was further characterized via HRMS, ELEMENTAL ANALYSIS, TGA and UV-VIS spectroscopy. Results of the MTS cell viability assay showed that several derivatives possessed cytotoxic activities that were several-fold more potent than cardamonin. Compound 19 was the most potent analogue possessing IC50 values of 13.2 µM and 0.7 µM against A549 and HK1 cells, corresponding to a 5- and 32-fold increase in activity, respectively. Furthermore, the active analogues, especially 19, have generally demonstrated lower toxicity towards normal MRC5 cells. SAR analysis showed the importance of the ketone and alkene groups for bioactivity, while substituting cardamonin’s phenolic groups with more polar moieties resulted in activity enhancement. As part of the SAR study and further exploration of chemical space, the effect of metal coordination on cytotoxicity was also investigated, but it was only possible to successfully obtain the Cu (II) complex of cardamonin (19), and results showed that the metal ion enhanced activity. 19 was also able to significantly inhibit the migration of A549 and HK1 cells. Further studies have shown that the most active analogue, 19, induced DNA damage resulting in G2/M-phase cell-cycle arrest in both cell lines. These events further led to the induction of apoptosis by 19 via caspase-3/7 and caspase-9 activation, PARP cleavage and downregulation of Mcl-1 expression. Finally, 19 inhibited the expression levels of p-mTOR and p-4EBP1. These data indicated that 19 exerted its anticancer activity, at least in part, via inhibition of the mTOR signalling pathway

Measurement of the VH,H → ττ process with the ATLAS detector at 13 TeV

A measurement of the Standard Model Higgs boson produced in association with a W or Z boson and decaying into a pair of τ-leptons is presented. This search is based on proton-proton collision data collected at √s = 13 TeV by the ATLAS experiment at the LHC corresponding to an integrated luminosity of 140 fb−1. For the Higgs boson candidate, only final states with at least one τ-lepton decaying hadronically (τ →hadrons + vτ ) are considered. For the vector bosons, only leptonic decay channels are considered: Z → ℓℓ and W → ℓvℓ, with ℓ = e, μ. An excess of events over the expected background is found with an observed (expected) significance of 4.2 (3.6) standard deviations, providing evidence of the Higgs boson produced in association with a vector boson and decaying into a pair of τ-leptons. The ratio of the measured cross-section to the Standard Model prediction is μττ VH = 1.28 +0.30 −0.29 (stat.) +0.25 −0.21 (syst.). This result represents the most accurate measurement of the VH(ττ) process achieved to date

The ATLAS trigger system for LHC Run 3 and trigger performance in 2022

The ATLAS trigger system is a crucial component of the ATLAS experiment at the LHC. It is responsible for selecting events in line with the ATLAS physics programme. This paper presents an overview of the changes to the trigger and data acquisition system during the second long shutdown of the LHC, and shows the performance of the trigger system and its components in the proton-proton collisions during the 2022 commissioning period as well as its expected performance in proton-proton and heavy-ion collisions for the remainder of the third LHC data-taking period (2022–2025)

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at √s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into diferent pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at √s = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, tt¯, and tb) or third-generation leptons (τν and τ τ ) are included in this kind of combination for the frst time. A simplifed model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confdence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion

Searches for exclusive Higgs boson decays into D⁎γ and Z boson decays into D0γ and Ks0γ in pp collisions at √s = 13 TeV with the ATLAS detector

Searches for exclusive decays of the Higgs boson into D⁎γ and of the Z boson into D0γ and Ks0γ can probe flavour-violating Higgs boson and Z boson couplings to light quarks. Searches for these decays are performed with a pp collision data sample corresponding to an integrated luminosity of 136.3 fb−1 collected at s=13TeV between 2016–2018 with the ATLAS detector at the CERN Large Hadron Collider. In the D⁎γ and D0γ channels, the observed (expected) 95% confidence-level upper limits on the respective branching fractions are B(H→D⁎γ)<1.0(1.2)×10−3, B(Z→D0γ)<4.0(3.4)×10−6, while the corresponding results in the Ks0γ channel are B(Z→Ks0γ)<3.1(3.0)×10−6

Beam-induced backgrounds measured in the ATLAS detector during local gas injection into the LHC beam vacuum

Inelastic beam-gas collisions at the Large Hadron Collider (LHC), within a few hundred metres of the ATLAS experiment, are known to give the dominant contribution to beam backgrounds. These are monitored by ATLAS with a dedicated Beam Conditions Monitor (BCM) and with the rate of fake jets in the calorimeters. These two methods are complementary since the BCM probes backgrounds just around the beam pipe while fake jets are observed at radii of up to several metres. In order to quantify the correlation between the residual gas density in the LHC beam vacuum and the experimental backgrounds recorded by ATLAS, several dedicated tests were performed during LHC Run 2. Local pressure bumps, with a gas density several orders of magnitude higher than during normal operation, were introduced at different locations. The changes of beam-related backgrounds, seen in ATLAS, are correlated with the local pressure variation. In addition the rates of beam-gas events are estimated from the pressure measurements and pressure bump profiles obtained from calculations. Using these rates, the efficiency of the ATLAS beam background monitors to detect beam-gas events is derived as a function of distance from the interaction point. These efficiencies and characteristic distributions of fake jets from the beam backgrounds are found to be in good agreement with results of beam-gas simulations performed with theFluka Monte Carlo programme

Measurement of vector boson production cross sections and their ratios using pp collisions at √s = 13.6 TeV with the ATLAS detector

Abstract available from publisher's website

Evidence of pair production of longitudinally polarised vector bosons and study of CP properties in ZZ → 4ℓ events with the ATLAS detector at √s = 13 TeV

A study of the polarisation and CP properties in ZZ production is presented. The used data set corresponds to an integrated luminosity of 140 fb−1 of proton-proton collisions at a centre-of-mass energy of 13 TeV recorded by the ATLAS detector at the Large Hadron Collider. The ZZ candidate events are reconstructed using two same-flavour opposite-charge electron or muon pairs. The production of two longitudinally polarised Z bosons is measured with a significance of 4.3 standard deviations, and its cross-section is measured in a fiducial phase space to be 2.45 ± 0.60 fb, consistent with the next-to-leading-order Standard Model prediction. The inclusive differential cross-section as a function of a CP-sensitive angular observable is also measured. The results are used to constrain anomalous CP-odd neutral triple gauge couplings