Le travail scientifique présenté dans cette thèse s’appuie sur des collisions proton proton, à 13 TeV dans le centre de masse, produite par le grand collisionneur de Hadron (LHC) et enregistrées entre 2015 et 2017 par le détecteur ATLAS. Après une brève introduction sur le programme de physique du LHC, le premier chapitre donne un aperçu complet du contexte et des motivations théorique. Ensuite une description complète du détecteur ATLAS et plus généralement de l’ensemble expérimental est donnée. Le troisième chapitre traite d’une des mesures des performances du calorimètre électromagnétique ATLAS, à savoir l’étude des efficacités identification électronique à l’aide de W se désintégrant en électrons et neutrinos.Dans les chapitres suivants, le coeur de cette thèse, la recherche et l’étude de la production associée de boson de Higgs avec une paire de quark top, appelée production ttH, est traitée dans le schéma du modèle Standard et au-delà. L’observation de la production ttH avec le détecteur ATLAS a été récemment annoncée en 2018 et représente une étape importante pour le domaine de la physique des hautes énergies. Afin d’élargir le spectre de cette analyse tth au-delà du SM, cet état final du canal 4L a aussi été étudié dans le cadre de la recherche de bosons de Higgs doublement chargés se désintégrant en W$^{\pm}$W$^{\pm}$, H$^{\pm \pm} \rightarrow $ W$^{\pm}$W$^{\pm}$. En conclusions, les perspectives sur les futurs résultats scientifiques dans le modèle Standard (SM) ainsi que au-delà de SM (BSM) qui pourraient être atteint en utilisant les statistiques complètes des Run1 et Run2 combinés sont donnés. / The scientific work presented in this thesis is based on proton proton collision produced, at 13 TeV in the center of mass, created by the Large Hadron Collider (LHC) and recorded between 2015 and 2017 by the ATLAS detector.After a short introduction on the physics program at LHC, the first chapter gives a comprehensive overview of the theoretical context and motivation. Then a complete description of the ATLAS detector and more generally the experimental setup is given with a highlight on the different physics objects used in this research.The third chapter is dealing with a measure of the performances of the ATLAS electromagnetic calorimeter, namely the study of the electron identification efficiencies using W decaying into electrons and neutrinos events.In the following chapters, the core of this thesis work, the search and study of the associated Higgs boson production with top quark pair, so-called ttH production, within the Standard Model schema and beyond is treated. The observation for ttH production with the ATLAS detector recently announced in 2018 represents a significant milestone for the High-Energy Physics field. In order to broaden the spectrum of this ttH analysis beyond the SM, this 4L channel final states was also studied in the context of the search for doubly charged Higgs boson decaying into W±W±, H±±→W±W±.In conclusions, future prospects in Standard Model (SM) as well as Beyond SM (BSM) scientific results that could be reached using the full Run1 and Run2 combined available statistics are given.

Um dos principais fatores de risco de doenças cardiovasculares, a hipercolesterolemia afeta um quinto da população brasileira, e é atualmente a principal causa de morte no Brasil e segunda maior de internações hospitalares, segundo a Sociedade Brasileira de Cardiologia. São utilizados agentes hipolipemiantes nos pacientes com propensão a doenças cardiovasculares associadas. A sinvastatina pertencente a classe dos inibidores da HMG-CoA redutase (3-hidroxi-3-metilglutaril-coenzima A) e o ezetimiba pertencente a classe dos inibidores da absorção do colesterol são fármacos hipolipemiantes. Este trabalho possui como objetivo o desenvolvimento e a validação de métodos bioanalíticos através da cromatografia liquida de alta eficiência acoplada ao detector de espectrometria de massas para a determinação simultânea quantitativa de ezetimiba e sinvastatina e seus metabólitos em plasma humano. O presente trabalho foi dividido nas seguintes etapas: (i) obtenção das amostras de pacientes provenientes do HU onde foi administrado a associação ezetimiba+sinvastatina, (ii) obtenção dos padrões de ezetimiba, sinvastatina e padrão interno, (iii) caracterização dos fármacos utilizando técnicas de análises térmicas, ressonância magnética nuclear e espectrometria de infra-vermelho, (iv) obtenção dos padrões dos metabólitos de ezetimiba (ezetimiba glucoronideo) e sinvastatina (sinvastatina hydroxy acid ammonium salt), (v) seleção do método analítico, fase móvel e tipo de extração nas amostras de plasma compatível com o detector de espectrometria de massas e (vi) teste no cromatógrafo líquido de alta eficiência acoplado ao detector de espectrômetro de massas. A separação cromatográfica foi realizada utilizando coluna Poroshell 50mm x 2,1mm, com partícula de 1,8 µm, eluição isocrática usando ácido fórmico 0,1%: acetonitrila (50:50, v/v), vazão 0,7 mL/min e volume de injeção de 10 µL. A temperatura da coluna foi de 30ºC e a detecção foi realizada em equipamento do tipo QTOF, usando fonte ESI no modo positivo para o ezetimiba e sinvastatina e modo negativo para o ezetimiba glucoronideo e sinvastatttina hidroxi-ácida. A monitoração dos íons produto foram: ezetimiba (m/z 409,1489>392,3123), sinvastatina (m/z 418,2719>419,2892), ezetimiba glucoronídeo (m/z 585,1810>521,0673) e sinvastatina hidroxi-ácida (m/z 453,3090>239,0501). Os métodos analíticos foram validados de acordo com os requerimentos vigentes da ANVISA e Farmacopéia Americana. Portanto, os métodos propostos demonstraram ser lineares, precisos, exatos e adequados para a quantificação simultânea de ezetimbe e sinvastatina e seus metabólitos (ezetimiba glucoronídeo e sinvastatina hidroxi-ácida) em plasma humano / One of the main risk factor, hypercholesterolemia which affects a fifth of the Brazilian people, particularly in people with more than 45 years old and currently is the main cause of death in Brazil and the second one of hospital admissions, according to the Brazilian Cardiology Society. It must be used lipid-lowering agents in patients with trend to cardiovascular disease associated. Simvastatin belongs to the HMG-CoA Reductase Inhibitors class ((3-hydroxy-3-metilglutaril-coenzyme A) and ezetimiba belongs to cholesterol absorption inhibitors and they are hypolipidemic. The aim of this work is to develop and validate Bioanalytical methodology using high performance liquid chromatography coupled to mass spectrometry (QTOF) to determinate simultaneously quantity of ezetimiba and simvastatin and their metabolites in human plasma. This study was divided into the following steps: (i) obtaining samples of patients from HU where ezetimibe+sinvastatina were administered, (ii) obtaining of ezetimibe, simvastatin and 4-methoxycoumarin (used as internal standard) standards, (iii) charactherization of drugs using techniques of termal analysis, nuclear magnetic ressonance and infra-red spectroscopy, (iv) obtaining of ezetimibe metabolite standard (glucuronide ezetimibe) and simvastatin metabolite standard (simvastatin hydroxy acid ammonium salt), (v) selection of analytical method, mobile phase and type of drugs extraction in human plasma samples to be used mass spectrometry, (vi) tests in the high efficiency liquid chromatography coupled to charged aerosol detector and mass spectrometry detector. Chromatographic separation was carried out using a Poroshell C18 column 50 mm x 2,1 mm with particle size of 1,8 µm, isocratic elution using 0,1% formic acid: acetonitrile (50:50, v/v), flow rate 0,7 mL/ min and injection volume of 10 µL. The column temperature was set at 30ºC and detection was performed in one equipament like QTOF, using ESI source, positive mode. Monitoring of the product ions were: ezetimibe (m/z 410,1557), simvastatina (m/z 419,2784), ezetimibe glucoronídeo (m/z 611,5756) and simvastatina hidroxi-ácida (m/z 552,2250). Analytical methods were validated according to the current ANVISA and United States Pharmacopoeia guidelines. Therefore, the proposed methods showed evidence to be linear, accurate and precision, suitable to the simultaneous quantitation of ezetimibe and simvastatin and their metabolites (ezetimibe glucoronídeo e sinvastatina hidroxi-ácida) in human plasma

No description available.

<p>This thesis is based on work done in two different experimental projects. </p><p>The first project, the Tau RICH, is a previously proposed τ-neutrino appearance experiment for the CERN neutrino beam at the Gran Sasso laboratory in Italy. The proposed experimental concept is based on the use of focusing RICH detectors with liquid radiator (C₆F₁₄). Simulations made with a Geant4 code show that in the proposed experimental set-up, Cherenkov light from delta electrons will constitute a severe background that in practice would render the experiment unfeasible.</p><p>The second project, ATLAS, is a general purpose detector at the CERN 14 TeV proton-proton collider LHC which will start operation in 2007. To make the reconstruction and selection of the events in ATLAS more accurate, complete and up-to-date information on the interaction of the produced particles with the detector is needed. A service program code, the Material Integration Service (MIS), has been developed which makes use of the detector descriptions already available in a Geant4 code and which uses a novel algorithm, based on line integrals evaluated within small volume elements that build up the detector. This code is demonstrated to constitute a practically useful tool of satisfactory performance and accuracy.</p><p>The charged Higgs boson production in the gluon-bottom quark mode, gb → tH^±, followed by charged Higgs decays into a chargino and a neutralino, is studied for a specific choice of values for the Minimal Supersymmetric Standard Model (MSSM) parameters. It is shown, using a Monte Carlo code to simulate the ATLAS detector and the assumed MSSM physics model, that for an integrated luminosity of 300 fb^-1, in the intermediate region 4 < tanβ < 10 where H^± decays to SM particles cannot be used for H^± discovery, charged Higgs decays to non-SM particles can be used for Higgs discovery at the 5 σ significance level.</p>

This thesis is based on work done in two different experimental projects. The first project, the Tau RICH, is a previously proposed τ-neutrino appearance experiment for the CERN neutrino beam at the Gran Sasso laboratory in Italy. The proposed experimental concept is based on the use of focusing RICH detectors with liquid radiator (C6F14). Simulations made with a Geant4 code show that in the proposed experimental set-up, Cherenkov light from delta electrons will constitute a severe background that in practice would render the experiment unfeasible. The second project, ATLAS, is a general purpose detector at the CERN 14 TeV proton-proton collider LHC which will start operation in 2007. To make the reconstruction and selection of the events in ATLAS more accurate, complete and up-to-date information on the interaction of the produced particles with the detector is needed. A service program code, the Material Integration Service (MIS), has been developed which makes use of the detector descriptions already available in a Geant4 code and which uses a novel algorithm, based on line integrals evaluated within small volume elements that build up the detector. This code is demonstrated to constitute a practically useful tool of satisfactory performance and accuracy. The charged Higgs boson production in the gluon-bottom quark mode, gb → tH±, followed by charged Higgs decays into a chargino and a neutralino, is studied for a specific choice of values for the Minimal Supersymmetric Standard Model (MSSM) parameters. It is shown, using a Monte Carlo code to simulate the ATLAS detector and the assumed MSSM physics model, that for an integrated luminosity of 300 fb-1, in the intermediate region 4 &lt; tanβ &lt; 10 where H± decays to SM particles cannot be used for H± discovery, charged Higgs decays to non-SM particles can be used for Higgs discovery at the 5 σ significance level.

This thesis describes the final precision mass measurements with SMILETRAP I, where a relative precision of &lt; 1 ppb (10-9) was reached routinely, and the development of SMILETRAP II, aiming for measurements with &lt; 0.1 ppb relative precision. The emphasis of the thesis is on the implementation of new techniques for achieving this precision improvement with SMILETRAP II. The Ramsey multiple-pulse excitation technique was tested at SMILETRAP I, and a reduction of the statistical uncertainty by factor three could by verified. The technique was applied in the last measurement with SMILETRAP I on H2+ and D+ ions. From these measurements the proton mass was deduced with a relative error of 0.18 ppb. It was found that temperature dependent magnetic field oscillations limited us from reducing the uncertainties further. A technical achievement of reducing the peak to peak temperature oscillation in the trapping region of SMILETRAP II by a factor four is presented, which should give an extended observation time and likewise improved precision. The new SMILETRAP II super-conducting magnet, with a slightly stronger field of 5.8 T compared with the previous of 4.7 T, was installed and adjusted.  A careful field alignment and reduction of inhomogeneities was done for minimizing the disturbances of the cyclotron frequency for improved precision. In that attempt, the localization and control of the trapped ion motion is also important. Thus a new cooling trap was set up. In the spring of 2009 coherent axial motion of a confined ion cloud was discovered in the cooling trap. By observation of the axial oscillations we can see the effects of evaporative cooling in the reduction of the axial energy distribution. Storing the ions up to 1 s in the cooling trap reduces the energy distribution by a factor of five. Other remarkable results of the ion oscillations are also reported. / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 1: In progress. Paper 3: Submitted.

For more than 30 years the Standard Model has been the theoretical foundation for particle physics. The theory has been verified successfully by experimental tests. Its biggest shortcoming is the non-discovery of the Higgs boson,responsible for giving the other particles masses. Despite its success there are hints that the Standard Model is not the complete theory and many extensions of it, such as supersymmetry, have been proposed. Extended theories often predict the existence of a charged Higgs boson and its detection will be a clear sign of physics beyond the Standard Model. The main focus in this thesis is on various phenomenological aspects of the charged Higgs boson. For favorable mass and couplings direct detection is shown to be possible at the Large Hadron Collider in production with an associated W boson. It is also shown how a light charged Higgs can have measurable effects on spin correlations in decays of pair-produced top quarks. The charged Higgs boson can also be seen indirectly, in for example B-meson decays, which can be used to put constraints on its mass and fermion couplings. Exclusion limits in two supersymmetric models are given together with a comparison with the discovery potentials for the LHC experiments. A tool for calculating properties, such as masses and decays, of both charged and neutral Higgs bosons in the Two-Higgs-Doublet Model is also presented. B-meson decays can also be used to test aspects of the strong interaction. Part of this thesis deals with improving and applying phenomenological models to B-meson decays. Although these models are not derived from first principles, their success shows that they capture important features of non-perturbative strong interactions.

Replicating the multi-hierarchical self-assembly of collagen (peptide chain to triple helix to nanofiber and, finally, to a hydrogel) has long attracted scientists, both from the fundamental science perspective of supramolecular chemistry and for the potential biomedical applications perceived in tissue engineering. In terms of triple helical formation, collagen is the most abundant protein in the human body with at least 28 types, yet research involving collagen mimetic systems has only recently began to consider the innate ability of collagen to control helix composition and register. Collagen triple helices can be homotrimeric or heterotrimeric and while some types of natural collagen form only one specific composition of helix, others can form multiple. It is critical to fully understand and, if possible, reproduce the control that native collagen has on helix composition and register. In terms of nanofiber formation, many approaches to drive the self-assembly of synthetic systems through the same steps as natural collagen have been partially successful, but none have simultaneously demonstrated all levels of structural assembly. In this work, advancements in the ability to control helix composition and replicate the multi-hierarchical assembly of collagen are described. Both positive and negative design for the assembly of AAB type collagen heterotrimers were utilized by promoting heterotrimer formation though the use of charged amino acids to form intra-helix electrostatic interactions, while simultaneously discouraging homotrimers, resulting in the identification of multiple peptide systems with full control over the composition of the resulting triple helix. Similar salt-bridged hydrogen bonds between charged residues were incorporated into nanofiber forming peptides, one of which successfully assembled into sticky-ended triple helices, nanofibers with characteristic triple helical packing visible in the solution state, and strong hydrogels that are degraded by collagenase at a similar rate to natural collagen. Together, these results provide a better understanding of the self-assembly of collagenous sequences as well as a novel design scheme for synthetic extracellular matrix mimetics with potential applications in regenerative medicine and drug delivery.

The precision of mass measurements in a Penning trap is directly proportional to an ion's charge state and can be increased by using highly charged ions (HCI) from an Electron Beam Ion Trap (EBIT). By bombarding the injected and trapped singly charged ions with an intense electron beam, the charge state of the ions is rapidly increased. To use this method for short-lived isotopes, very high electron beam current densities are required of the TITAN EBIT, built and commissioned at the Max-Planck-Institute for Nuclear Physics in Heidelberg, Germany and transported to TRIUMF for the TITAN on-line facility. This EBIT has produced charge states as high as Kr34+ and Ba54+ with electron beams of up to 500 mA and 27 keV. Once the EBIT is operational at full capacity (5 A, 60 keV), most species can be bred into a He-like configuration within tens of ms. / October 2006

The objective of this research is to design, fabricate, and demonstrate a microfabricated monolithic ion trap for applications in quantum computation and quantum simulation. Most current microfabricated ion trap designs are based on planar-segmented surface electrodes. Although promising scalability to trap arrays containing ten to one hundred ions, these planar designs suffer from the challenges of shallow trap depths, radial asymmetry of the confining potential, and electrode charging resulting from laser interactions with dielectric surfaces. In this research, the design, fabrication, and testing of a monolithic and symmetric two-level ion trap is presented. This ion trap overcomes the challenges of surface-electrode ion traps. Numerical electrostatic simulations show that this symmetric trap produces a deep (1 eV for 171Yb+ ion), radially symmetric RF confinement potential. The trap has an angled through-chip slot that allows back-side ion loading and generous through laser access, while avoiding surface-light scattering and dielectric charging that can corrupt the design control electrode compensating potentials. The geometry of the trap and its dimensions are optimized for trapping long and linear ion chains with equal spacing for use with quantum simulation problems and quantum computation architectures.