Constraints on new phenomena via Higgs boson couplings and invisible decays with the ATLAS detector

The ATLAS experiment at the LHC has measured the Higgs boson couplings and mass, and searched for invisible Higgs boson decays, using multiple production and decay channels with up to 4.7 fb−1 of pp collision data at √s=7 TeV and 20.3 fb−1 at √s=8 TeV. In the current study, the measured production and decay rates of the observed Higgs boson in the γγ, ZZ, W W , Zγ, bb, τ τ , and μμ decay channels, along with results from the associated production of a Higgs boson with a top-quark pair, are used to probe the scaling of the couplings with mass. Limits are set on parameters in extensions of the Standard Model including a composite Higgs boson, an additional electroweak singlet, and two-Higgs-doublet models. Together with the measured mass of the scalar Higgs boson in the γγ and ZZ decay modes, a lower limit is set on the pseudoscalar Higgs boson mass of m A > 370 GeV in the “hMSSM” simplified Minimal Supersymmetric Standard Model. Results from direct searches for heavy Higgs bosons are also interpreted in the hMSSM. Direct searches for invisible Higgs boson decays in the vector-boson fusion and associated production of a Higgs boson with W/Z (Z → ℓℓ, W/Z → jj) modes are statistically combined to set an upper limit on the Higgs boson invisible branching ratio of 0.25. The use of the measured visible decay rates in a more general coupling fit improves the upper limit to 0.23, constraining a Higgs portal model of dark matter.

Measurement of the t(t)over-barW and t(t)over-barZ production cross sections in pp collisions at root s=8 TeV with the ATLAS detector

The production cross sections of top-quark pairs in association with massive vector bosons have been measured using data from pp collisions at s√=8 TeV. The dataset corresponds to an integrated luminosity of 20.3 fb−1 collected by the ATLAS detector in 2012 at the LHC. Final states with two, three or four leptons are considered. A fit to the data considering the tt¯W and tt¯Z processes simultaneously yields a significance of 5.0σ (4.2σ) over the background-only hypothesis for tt¯W (tt¯Z) production. The measured cross sections are σtt¯W=369+100−91 fb and σtt¯Z=176+58−52 fb. The background-only hypothesis with neither tt¯W nor tt¯Z production is excluded at 7.1σ. All measurements are consistent with next-to-leading-order calculations for the tt¯W and tt¯Z processes.

A search for t(t)over-bar resonances using lepton-plus-jets events in proton-proton collisions at root s=8 TeV with the ATLAS detector

A search for new particles that decay into top quark pairs is reported. The search is performed with the ATLAS experiment at the LHC using an integrated luminosity of 20.3 fb−1 of proton-proton collision data collected at a centre-of-mass energy of s√=8 TeV. The lepton-plus-jets final state is used, where the top pair decays to W+bW−b¯¯, with one W boson decaying leptonically and the other hadronically. The invariant mass spectrum of top quark pairs is examined for local excesses or deficits that are inconsistent with the Standard Model predictions. No evidence for a top quark pair resonance is found, and 95% confidence-level limits on the production rate are determined for massive states in benchmark models. The upper limits on the cross-section times branching ratio of a narrow Z′ boson decaying to top pairs range from 4.2 pb to 0.03 pb for resonance masses from 0.4 TeV to 3.0 TeV. A narrow leptophobic topcolour Z′ boson with mass below 1.8 TeV is excluded. Upper limits are set on the cross-section times branching ratio for a broad colour-octet resonance with Γ/m = 15% decaying to tt¯. These range from 4.8 pb to 0.03 pb for masses from 0.4 TeV to 3.0 TeV. A Kaluza-Klein excitation of the gluon in a Randall-Sundrum model is excluded for masses below 2.2 TeV.

Measurement of the branching ratio Γ(Λ0b→ψ(2S)Λ0)/Γ(Λ0b→J/ψΛ0) with the ATLAS detector

An observation of the Λ0b→ψ(2S)Λ0 decay and a comparison of its branching fraction with that of the Λ0b→J/ψΛ0 decay has been made with the ATLAS detector in proton--proton collisions at s√=8TeV at the LHC using an integrated luminosity of 20.6fb−1. The J/ψ and ψ(2S) mesons are reconstructed in their decays to a muon pair, while the Λ0→pπ− decay is exploited for the Λ0 baryon reconstruction. The Λ0b baryons are reconstructed with transverse momentum pT>10GeV and pseudorapidity |η|<2.1. The measured branching ratio of the Λ0b→ψ(2S)Λ0 and Λ0b→J/ψΛ0 decays is Γ(Λ0b→ψ(2S)Λ0)/Γ(Λ0b→J/ψΛ0)=0.501±0.033(stat)±0.019(syst), lower than the expectation from the covariant quark model.

Synthesis, antiangiogenesis evaluation and molecular docking studies of 1-Aryl-3-[(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas: Discovery of a new substitution pattern for type II VEGFR-2 Tyr kinase inhibitors

The synthesis and biological evaluation of novel 1-aryl-3-[2-, 3- or 4-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 3, 4 and 5 as VEGFR-2 tyrosine kinase inhibitors, are reported. The 1-aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas 4a-4h, with the arylurea in the meta position to the thioether, showed the lowest IC50 values in enzymatic assays (10-206 nM), the most potent compounds 4d-4h (IC50 10-28 nM) bearing hydrophobic groups (Me, F, CF3 and Cl) in the terminal phenyl ring. A convincing rationalization was achieved for the highest potent compounds 4 as type II VEGFR-2 inhibitors, based on the simultaneous presence of: (1) the thioether linker and (2) the arylurea moiety in the meta position. For compounds 4, significant inhibition of Human Umbilical Vein Endothelial Cells (HUVECs) proliferation (BrdU assay), migration (wound-healing assay) and tube formation were observed at low concentrations. These compounds have also shown to increase apoptosis using the TUNEL assay. Immunostaining for total and phosphorylated (active) VEGFR-2 was performed by Western blotting. The phosphorylation of the receptor was significantly inhibited at 1.0 and 2.5 microM for the most promising compounds. Altogether, these findings point to an antiangiogenic effect in HUVECs.

In vitro digestion and stability assessment of b-lactoglobulin/riboflavin nanostructures

B-Lactoglobulin (b-Lg) is the major protein fraction of bovine whey serum and a primary gelling agent. b-Lg has a high nutritional value, is stable at low pH being highly resistant to proteolytic degradation in the stomach, besides, it has the ability of acting as an encapsulating agent. This study aims at assessing the ability of b-Lg nanostructures to associate a nutraceutical - i.e. riboflavin - and release it in a controlled manner throughout an in vitro gastrointestinal (GI) system. For this reason b-Lg nanostructures loaded with riboflavin were critically characterized in terms of their morphology (i.e. size, polydispersity, -potential and shape) by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and efficiency to associate to riboflavin through spectrofluorimetry. Furthermore, these nanocomplexes were evaluated in an in vitro GI model, simulating the physiological conditions. Stable b-Lg nanostructures were obtained at pH 6, of spherical shape, characterized by particle size of 172±1 nm, low polydispersity (i.e. PDI of 0.06±0.02), -potential of -32±3 mV and association efficiency (AE) of 26±1 %. b-Lg nanostructures showed to be stable upon their passage throughout stomach (i.e. particle size, PDI and potential of 248±10 nm, 0.18±0.03 and 18±3 mV, respectively). Concerning their passage throughout the intestine, such nanostructures were mostly degraded in the duodenum. Regarding riboflavin, a release of about 11 % was observed after their passage through stomach, while 35 %, 38 % and 5 % were the released percentages of the total riboflavin associated observed after passage through duodenum, jejunum and ileum, respectively. Hence,b-Lg nanostructures showed to be suitable carriers for riboflavin until the intestine, where their degradation occurs. b-Lg also showed to be structurally stable, under food simulant conditions (yoghurt simulant, composed of 3 % acetic acid), over 14 days, with a protective effect upon riboflavin activity, releasing it in a 7 day period.

Síntese de novas tieno[3,2-b]piridinas com potencial atividade biológica contendo 1,2,3-triazoles 1,4-dissubstituídos obtidos por reação "click" de ciclioadição azida-alquino catalisada por Cu(I)-CuAAC

Dissertação de mestrado em Química Medicinal