Evidence for the Higgs-boson Yukawa coupling to tau leptons with the ATLAS detector

Results of a search for H→ττ decays are presented, based on the full set of proton--proton collision data recorded by the ATLAS experiment at the LHC during 2011 and 2012. The data correspond to integrated luminosities of 4.5 fb−1 and 20.3 fb−1 at centre-of-mass energies of s√ = 7 TeV and s√ = 8 TeV respectively. All combinations of leptonic (τ→ℓνν¯ with ℓ=e,μ) and hadronic (τ→hadrons ν) tau decays are considered. An excess of events over the expected background from other Standard Model processes is found with an observed (expected) significance of 4.5 (3.4) standard deviations. This excess provides evidence for the direct coupling of the recently discovered Higgs boson to fermions. The measured signal strength, normalised to the Standard Model expectation, of μ=1.43+0.43−0.37 is consistent with the predicted Yukawa coupling strength in the Standard Model.

Identification and energy calibration of hadronically decaying tau leptons with the ATLAS experiment in pp collisions at s√=8 TeV

This paper describes the trigger and offline reconstruction, identification and energy calibration algorithms for hadronic decays of tau leptons employed for the data collected from pp collisions in 2012 with the ATLAS detector at the LHC center-of-mass energy s√ = 8 TeV. The performance of these algorithms is measured in most cases with Z decays to tau leptons using the full 2012 dataset, corresponding to an integrated luminosity of 20.3 fb−1. An uncertainty on the offline reconstructed tau energy scale of 2% to 4%, depending on transverse energy and pseudorapidity, is achieved using two independent methods. The offline tau identification efficiency is measured with a precision of 2.5% for hadronically decaying tau leptons with one associated track, and of 4% for the case of three associated tracks, inclusive in pseudorapidity and for a visible transverse energy greater than 20 GeV. For hadronic tau lepton decays selected by offline algorithms, the tau trigger identification efficiency is measured with a precision of 2% to 8%, depending on the transverse energy. The performance of the tau algorithms, both offline and at the trigger level, is found to be stable with respect to the number of concurrent proton--proton interactions and has supported a variety of physics results using hadronically decaying tau leptons at ATLAS.

Female hippocampus vulnerability to environmental stress, a precipitating factor in tau aggregation pathology

Tau-mediated neurodegeneration is a central event in Alzheimer's disease (AD) and other tauopathies. Consistent with suggestions that lifetime stress may be a clinically-relevant precipitant of AD pathology, we previously showed that stress triggers tau hyperphosphorylation and accumulation; however, little is known about the etiopathogenic interaction of chronic stress with other AD risk factors, such as sex and aging. This study focused on how these various factors converge on the cellular mechanisms underlying tau aggregation in the hippocampus of chronically stressed male and female (middle-aged and old) mice expressing the most commonly found disease-associated Tau mutation in humans, P301L-Tau. We report that environmental stress triggers memory impairments in female, but not male, P301L-Tau transgenic mice. Furthermore, stress elevates levels of caspase-3-truncated tau and insoluble tau aggregates exclusively in the female hippocampus while it also alters the expression of the molecular chaperones Hsp90, Hsp70, and Hsp105, thus favoring accumulation of tau aggregates. Our findings provide new insights into the molecular mechanisms through which clinically-relevant precipitating factors contribute to the pathophysiology of AD. Our data point to the exquisite sensitivity of the female hippocampus to stress-triggered tau pathology.

Aging and Alzheimer's disease: Searching for novel molecular cues

Tese de Doutoramento em Ciências da Saúde

Search for a Heavy Neutral Particle Decaying to eμ, eτ, or μτ in pp Collisions at s√=8 TeV with the ATLAS Detector

This Letter presents a search for a heavy neutral particle decaying into an opposite-sign different-flavor dilepton pair, e±μ∓, e±τ∓, or μ±τ∓ using 20.3 fb−1 of pp collision data at s√=8 TeV collected by the ATLAS detector at the LHC. The numbers of observed candidate events are compatible with the Standard Model expectations. Limits are set on the cross section of new phenomena in two scenarios: the production of ν~τ in R-parity-violating supersymmetric models and the production of a lepton-flavor-violating Z′ vector boson.

Search for Higgs bosons decaying to aa in the μμττ final state in pp collisions at s√= 8 TeV with the ATLAS experiment

A search for the decay to a pair of new particles of either the 125 GeV Higgs boson (h) or a second CP-even Higgs boson (H) is presented. The dataset correspods to an integrated luminosity of 20.3 fb−1 of pp collisions at s√= 8 TeV recorded by the ATLAS experiment at the LHC in 2012. The search was done in the context of the next-to-minimal supersymmetric standard model, in which the new particles are the lightest neutral pseudoscalar Higgs bosons (a). One of the two a bosons is required to decay to two muons while the other is required to decay to two τ-leptons. No significant excess is observed above the expected backgrounds in the dimuon invariant mass range from 3.7 GeV to 50 GeV. Upper limits are placed on the production of h→aa relative to the Standard Model gg→h production, assuming no coupling of the a boson to quarks. The most stringent limit is placed at 3.5% for ma= 3.75 GeV. Upper limits are also placed on the production cross section of H→aa from 2.33 pb to 0.72 pb, for fixed ma = 5 GeV with mH ranging from 100 GeV to 500 GeV.

A search for high-mass resonances decaying to τ+τ− in pp collisions at s√=8 TeV with the ATLAS detector

A search for high-mass resonances decaying into τ+τ− final states using proton-proton collisions at s√=8 TeV produced by the Large Hadron Collider is presented. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 19.5-20.3 fb−1. No statistically significant excess above the Standard Model expectation is observed; 95% credibility upper limits are set on the cross section times branching fraction of Z′ resonances decaying into τ+τ− pairs as a function of the resonance mass. As a result, Z′ bosons of the Sequential Standard Model with masses less than 2.02 TeV are excluded at 95% credibility. The impact of the fermionic couplings on the Z′ acceptance is investigated and limits are also placed on a Z′ model that exhibits enhanced couplings to third-generation fermions.

Searches for heavy long-lived charged particles with the ATLAS detector in proton--proton collisions at s√ = 8 TeV

Searches for heavy long-lived charged particles are performed using a data sample of 19.8 fb−1 from proton--proton collisions at a centre-of-mass energy of s√ = 8 TeV collected by the ATLAS detector at the Large Hadron Collider. No excess is observed above the estimated background and limits are placed on the mass of long-lived particles in various supersymmetric models. Long-lived tau sleptons in models with gauge-mediated symmetry breaking are excluded up to masses between 440 and 385 GeV for tan(beta) between 10 and 50, with a 290 GeV limit in the case where only direct tau slepton production is considered. In the context of simplified LeptoSUSY models, where sleptons are stable and have a mass of 300 GeV, squark and gluino masses are excluded up to a mass of 1500 and 1360 GeV, respectively. Directly produced charginos, in simplified models where they are nearly degenerate to the lightest neutralino, are excluded up to a mass of 620 GeV. R-hadrons, composites containing a gluino, bottom squark or top squark, are excluded up to a mass of 1270, 845 and 900 GeV, respectively, using the full detector; and up to a mass of 1260, 835 and 870 GeV using an approach disregarding information from the muon spectrometer.

Search for new phenomena in events with three or more charged leptons in pp collisions at 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 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 eτ or μτ, 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 Λ, with the strongest mass constraints arising in regions where the mass equals Λ. 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.

Modelling Z→ττ processes in ATLAS with τ-embedded Z→μμ data

This paper describes the concept, technical realisation and validation of a largely data-driven method to model events with Z→ττ decays. In Z→μμ events selected from proton-proton collision data recorded at s√=8 TeV with the ATLAS experiment at the LHC in 2012, the Z decay muons are replaced by τ leptons from simulated Z→ττ decays at the level of reconstructed tracks and calorimeter cells. The τ lepton kinematics are derived from the kinematics of the original muons. Thus, only the well-understood decays of the Z boson and τ leptons as well as the detector response to the τ decay products are obtained from simulation. All other aspects of the event, such as the Z boson and jet kinematics as well as effects from multiple interactions, are given by the actual data. This so-called τ-embedding method is particularly relevant for Higgs boson searches and analyses in ττ final states, where Z→ττ decays constitute a large irreducible background that cannot be obtained directly from data control samples.

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.

Stress-triggered synaptic malfunction: a gate along the path from depressionto dementia

Tese de Doutoramento em Ciências da Saúde.

Role of sirtuin 3 on mitochondrial dynamics in Huntington's disease striatal cells

Dissertação de mestrado em Genética Molecular

In vitro phosphorylation as tool for modification of silk and keratin fibrous materials

An overview is given of the recent work on in vitro enzymatic phosphorylation of silk fibroin and human hair keratin. Opposing to many chemical "conventional" approaches, enzymatic phosphorylation is in fact a mild reaction and the treatment falls within "green chemistry" approach. Silk and keratin are not phosphorylated in vivo, but in vitro. This enzyme-driven modification is a major technological breakthrough. Harsh chemical chemicals are avoided, and mild conditions make enzymatic phosphorylation a real "green chemistry" approach. The current communication presents a novel approach stating that enzyme phosphorylation may be used as a tool to modify the surface charge of biocompatible materials such as keratin and silk.