Introdução: O metilfenidato de liberação imediata (MFD-LI) é um psicofármaco receitado mundialmente para o tratamento do Transtorno de Déficit de Atenção/hiperatividade (TDAH). Embora eficaz, o MFD-LI está associado a problemas de adesão ao tratamento, uma vez que os pacientes necessitam ingerir os comprimidos várias vezes ao dia. O Spheroidal Oral Drug Absorption System (SODAS™) é uma formulação de metilfenidato de liberação prolongada (MFD-LP) que mimetiza a administração de MFD-LI duas vezes ao dia, e que apresenta menor flutuação nos níveis séricos. Nesta formulação, cinqüenta por cento dos grânulos com revestimento para liberação entérica são liberados aproximadamente 4 horas após a administração, proporcionando um perfil de ação semelhante a duas tomadas ao dia do MFD-LI. O MFD SODAS™ libera de imediato 50% do medicamento, proporcionando um rápido início de ação quando comparado ao sistema de liberação OROS®. Poucos estudos avaliaram a troca do MFD-LI para o MFD-LP, sendo que desses, apenas crianças e adolescentes foram avaliados, e nenhum verificou os preditores de insatisfação da troca do MFD-LI para o MFD-LP. Objetivos: Este estudo tem como objetivo avaliar os sintomas de TDAH, ou preditores de insatisfação e/ou desistência do tratamento naqueles pacientes clinicamente estáveis que fizeram a troca do MDF-LI para o MFD SODAS™. Método: Os critérios de inclusão foram: diagnóstico de TDAH de acordo com os critérios do DSM-IV, e estabilidade de sintomas com o uso do MFD-LI. Os critérios de exclusão foram: condição clínica coexistente que pudesse impedir a prescrição de MFD SODAS™; diagnóstico de abuso ou dependência de álcool e/ou drogas de abuso; diagnóstico prévio de retardo mental moderado; tratamento psicoterápico concomitante. Este é um ensaio clínico aberto realizado em oito semanas. Os pacientes foram designados a receber doses de MFD SODAS™ de acordo com a dose de MFD-LI previamente estabelecida. A eficácia foi avaliada através das escalas SNAP-IV e CGI-S, e eventos adversos através da Barkley's Side Effect Rating Scale (SERS). Foi solicitado aos participantes que classificassem sua satisfação com o tratamento através de uma escala Likert de 5 pontos. Também foram avaliados os seguintes potenciais preditores de resposta: sexo, idade, etnia, nível socioeconômico, comorbidades, subtipos de TDAH, resultados das escalas SNAP-IV e SERS no baseline, tempo de tratamento, tratamento farmacológico concomitante, dose de MFD-LI prévia ao início do estudo e a existência de pausa do tratamento nos finais de semana. Resultados: A partir de uma amostra total de 207 crianças, adolescentes e adultos (provenientes do ambulatório adulto e infantil de transtorno de déficit de atenção/hiperatividade do Hospital de Clínicas de Porto Alegre) foi possível contatar 133 pacientes, os quais sessenta e dois pacientes foram elegíveis a participar do estudo, e 47 completaram as oito semanas de tratamento. Não se encontrou diferença significativa no escore total do SNAP-IV durante o protocolo - baseline, semana 4 e 8 [F(1, 51,26) =0,012; p=0,913]. Ao todo, 46 (74,2%) dos pacientes relataram estar satisfeitos com o novo tratamento, 16 (25,8%) estavam insatisfeitos ou saíram do protocolo. Nas análises univariadas, foi detectada uma tendência para a associação entre etnia e insatisfação (p=0.05). Não se encontrou uma diferença significativa nos escores da SERS durante o ensaio clínico [F(1, 111,49) =0,748; p=0,389]. Em onze eventos adversos ocorreram ao menos 5% em alguma das avaliações (baseline, 4ª ou 8ª semana). Um adulto, que apresentava uma doença cardiovascular previamente ao estudo, apresentou um acidente vascular cerebral hemorrágico (AVCH) após a quarta semana de tratamento, evoluindo ao óbito após três semanas. Conclusão: Poucos estudos abordaram os sintomas de TDAH após a troca do MFD-LI para qualquer formulação de MFD-LP, e nenhum estudo prévio foi conduzido em populações de países em desenvolvimento ou em amostras com adultos. A taxa de satisfação encontrada (74,2%) na troca do MFD-LI para MFD SODAS™ possivelmente reflete a conveniência da dose única diária deste MFD-LP, como já especulado em estudos prévios. Não foram identificados fatores preditores de insatisfação. O número médio de efeitos colaterais pode ser considerado alto, mas isso pode ser o resultado do uso de uma escala de avaliação adequada, diferentemente do relato espontâneo do evento adverso. Não foi possível encontrar uma relação direta entre os efeitos do MFD SODAS™ e a morte por AVCH ocorrida em um dos sujeitos da amostra. Entretanto, o evento cardiovascular ocorrido sugere extrema cautela ao medicar pacientes com doenças cardiovasculares, conforme proposto pelo FDA. Os achados desse estudo sugerem que o MFD SODAS™ possui eficácia e perfil de eventos adversos similares ao MFD-LI. / Introduction: Immediate-release methylphenidate (MPH-IR) is a pharmacological treatment prescribed worldwide for patients with attention-deficit/hyperactivity disorder (ADHD). The MPH-IR, although highly efficacious, need to be used more than once a day, and consequently might be associated with poor adherence. The Spheroidal Oral Drug Absorption System (SODAS™) is one type of MPH-ER (Extended-release methylphenidate) that mimics the twice-daily administration of MPH-immediate release, but presents less peak and trough fluctuations. This formulation allows the immediate release of 50% of the drug, providing a rapid onset if compared with OROS® formulation. Few studies have evaluated specifically the switching from MPH-IR to MPH-ER. All previous studies accessed only children and adolescents; none evaluated switching to MPH SODAS™ and no predictors of treatment dissatisfaction were mentioned. Objectives: The present study aims to assess ADHD symptoms for 08 weeks after switching from MPH-IR to MPH SODAS™ in clinically stable patients, and to identify predictors of dissatisfaction with MPH SODAS™, and/ or withdrawal from the protocol. Method: The inclusion criteria were: ADHD diagnosis according to the DSM-IV criteria and clinical stability with MPH-IR. The exclusion criteria were: a clinically coexisting medical condition interfering with the administration of MPH SODAS™; previous diagnosis of alcohol and/or drug abuse or dependence; previous diagnosis of moderate mental retardation; concomitant psychotherapy. This is an 8-week open clinical trial. Patients were assigned to doses of MPH SODAS™ according to their pre-study dose of MPH-IR. Assessment of efficacy and side effects was performed by means of the SNAP-IV, CGI-S, Barkley's Side Effect Rating Scale (SERS). Subjects were also asked to report their satisfaction with the treatment in a 5-point Likert scale. We also evaluated the following potential predictors of treatment response: sex, age, ethnicity, socioeconomic status, comorbidities, baseline scores on the SNAP-IV, and SERS, length of treatment, concomitant treatment, previous prescribed dose of MPH-IR, and pause of treatment on weekends. Results: From a total sample of 207 children, adolescents and adults (enrolled from the ADHD outpatient clinic at both Adult and Child and Adolescent Psychiatric Division of Hospital de Clínicas de Porto Alegre) we were able to re-contact 133 patients, where sixty-two patients were eligible to the clinical trial, and 47 completed the 08 weeks of treatment. There was no significant change in the total score of the SNAP-IV during the protocol – baseline, week 4 and 8 [F(1, 51.26)=0.012; p=0.913]. Overall, 46 (74.2%) patients had reported to be satisfied with the new treatment, and 16 (25.8%) were dissatisfied or withdrew from the protocol. In univariate analyses, only ethnicity (p=0.05) were associated with dissatisfaction. No significant change in the SERS score was found during the protocol [F(1, 111.49)=0.748; p=0.389]. Eleven adverse events occurring in at least 5% of the group in any assessment (baseline, 04 or 08 weeks) were observed according to SERS. One adult, with previous cardiovascular disease, presented a hemorrhagic cerebral vascular accident (CVA) after the forth week assessment, resulting in her obit. Conclusion: There is a scarcity of research assessing the switch from MPH-IR to different forms of MPH-ER, and none across the life cycle or in populations from developing countries. The 74.2% of satisfaction with the new treatment may reflect the convenience of the once-a-day dosing of the MPH SODAS™. No predictor of dissatisfaction/withdrawal from the trial was found. The number of adverse events reported during the protocol could be considered high, but this can be the result of the use of an appropriate assessment scale, rather than monitoring only by spontaneous report. It was not possible to find a direc relationship between the MPH SODAS™ and death from a CVA occurred in one of the subjects. However, the cardiovascular event found during the trial, suggest extreme caution when medicating patients with cardiovascular diseases as recently proposed by the FDA. Findings from this study suggest that MPH SODAS™ has similar efficacy and adverse event profile than MPH-IR.

Introdução: O metilfenidato de liberação imediata (MFD-LI) é um psicofármaco receitado mundialmente para o tratamento do Transtorno de Déficit de Atenção/hiperatividade (TDAH). Embora eficaz, o MFD-LI está associado a problemas de adesão ao tratamento, uma vez que os pacientes necessitam ingerir os comprimidos várias vezes ao dia. O Spheroidal Oral Drug Absorption System (SODAS™) é uma formulação de metilfenidato de liberação prolongada (MFD-LP) que mimetiza a administração de MFD-LI duas vezes ao dia, e que apresenta menor flutuação nos níveis séricos. Nesta formulação, cinqüenta por cento dos grânulos com revestimento para liberação entérica são liberados aproximadamente 4 horas após a administração, proporcionando um perfil de ação semelhante a duas tomadas ao dia do MFD-LI. O MFD SODAS™ libera de imediato 50% do medicamento, proporcionando um rápido início de ação quando comparado ao sistema de liberação OROS®. Poucos estudos avaliaram a troca do MFD-LI para o MFD-LP, sendo que desses, apenas crianças e adolescentes foram avaliados, e nenhum verificou os preditores de insatisfação da troca do MFD-LI para o MFD-LP. Objetivos: Este estudo tem como objetivo avaliar os sintomas de TDAH, ou preditores de insatisfação e/ou desistência do tratamento naqueles pacientes clinicamente estáveis que fizeram a troca do MDF-LI para o MFD SODAS™. Método: Os critérios de inclusão foram: diagnóstico de TDAH de acordo com os critérios do DSM-IV, e estabilidade de sintomas com o uso do MFD-LI. Os critérios de exclusão foram: condição clínica coexistente que pudesse impedir a prescrição de MFD SODAS™; diagnóstico de abuso ou dependência de álcool e/ou drogas de abuso; diagnóstico prévio de retardo mental moderado; tratamento psicoterápico concomitante. Este é um ensaio clínico aberto realizado em oito semanas. Os pacientes foram designados a receber doses de MFD SODAS™ de acordo com a dose de MFD-LI previamente estabelecida. A eficácia foi avaliada através das escalas SNAP-IV e CGI-S, e eventos adversos através da Barkley's Side Effect Rating Scale (SERS). Foi solicitado aos participantes que classificassem sua satisfação com o tratamento através de uma escala Likert de 5 pontos. Também foram avaliados os seguintes potenciais preditores de resposta: sexo, idade, etnia, nível socioeconômico, comorbidades, subtipos de TDAH, resultados das escalas SNAP-IV e SERS no baseline, tempo de tratamento, tratamento farmacológico concomitante, dose de MFD-LI prévia ao início do estudo e a existência de pausa do tratamento nos finais de semana. Resultados: A partir de uma amostra total de 207 crianças, adolescentes e adultos (provenientes do ambulatório adulto e infantil de transtorno de déficit de atenção/hiperatividade do Hospital de Clínicas de Porto Alegre) foi possível contatar 133 pacientes, os quais sessenta e dois pacientes foram elegíveis a participar do estudo, e 47 completaram as oito semanas de tratamento. Não se encontrou diferença significativa no escore total do SNAP-IV durante o protocolo - baseline, semana 4 e 8 [F(1, 51,26) =0,012; p=0,913]. Ao todo, 46 (74,2%) dos pacientes relataram estar satisfeitos com o novo tratamento, 16 (25,8%) estavam insatisfeitos ou saíram do protocolo. Nas análises univariadas, foi detectada uma tendência para a associação entre etnia e insatisfação (p=0.05). Não se encontrou uma diferença significativa nos escores da SERS durante o ensaio clínico [F(1, 111,49) =0,748; p=0,389]. Em onze eventos adversos ocorreram ao menos 5% em alguma das avaliações (baseline, 4ª ou 8ª semana). Um adulto, que apresentava uma doença cardiovascular previamente ao estudo, apresentou um acidente vascular cerebral hemorrágico (AVCH) após a quarta semana de tratamento, evoluindo ao óbito após três semanas. Conclusão: Poucos estudos abordaram os sintomas de TDAH após a troca do MFD-LI para qualquer formulação de MFD-LP, e nenhum estudo prévio foi conduzido em populações de países em desenvolvimento ou em amostras com adultos. A taxa de satisfação encontrada (74,2%) na troca do MFD-LI para MFD SODAS™ possivelmente reflete a conveniência da dose única diária deste MFD-LP, como já especulado em estudos prévios. Não foram identificados fatores preditores de insatisfação. O número médio de efeitos colaterais pode ser considerado alto, mas isso pode ser o resultado do uso de uma escala de avaliação adequada, diferentemente do relato espontâneo do evento adverso. Não foi possível encontrar uma relação direta entre os efeitos do MFD SODAS™ e a morte por AVCH ocorrida em um dos sujeitos da amostra. Entretanto, o evento cardiovascular ocorrido sugere extrema cautela ao medicar pacientes com doenças cardiovasculares, conforme proposto pelo FDA. Os achados desse estudo sugerem que o MFD SODAS™ possui eficácia e perfil de eventos adversos similares ao MFD-LI. / Introduction: Immediate-release methylphenidate (MPH-IR) is a pharmacological treatment prescribed worldwide for patients with attention-deficit/hyperactivity disorder (ADHD). The MPH-IR, although highly efficacious, need to be used more than once a day, and consequently might be associated with poor adherence. The Spheroidal Oral Drug Absorption System (SODAS™) is one type of MPH-ER (Extended-release methylphenidate) that mimics the twice-daily administration of MPH-immediate release, but presents less peak and trough fluctuations. This formulation allows the immediate release of 50% of the drug, providing a rapid onset if compared with OROS® formulation. Few studies have evaluated specifically the switching from MPH-IR to MPH-ER. All previous studies accessed only children and adolescents; none evaluated switching to MPH SODAS™ and no predictors of treatment dissatisfaction were mentioned. Objectives: The present study aims to assess ADHD symptoms for 08 weeks after switching from MPH-IR to MPH SODAS™ in clinically stable patients, and to identify predictors of dissatisfaction with MPH SODAS™, and/ or withdrawal from the protocol. Method: The inclusion criteria were: ADHD diagnosis according to the DSM-IV criteria and clinical stability with MPH-IR. The exclusion criteria were: a clinically coexisting medical condition interfering with the administration of MPH SODAS™; previous diagnosis of alcohol and/or drug abuse or dependence; previous diagnosis of moderate mental retardation; concomitant psychotherapy. This is an 8-week open clinical trial. Patients were assigned to doses of MPH SODAS™ according to their pre-study dose of MPH-IR. Assessment of efficacy and side effects was performed by means of the SNAP-IV, CGI-S, Barkley's Side Effect Rating Scale (SERS). Subjects were also asked to report their satisfaction with the treatment in a 5-point Likert scale. We also evaluated the following potential predictors of treatment response: sex, age, ethnicity, socioeconomic status, comorbidities, baseline scores on the SNAP-IV, and SERS, length of treatment, concomitant treatment, previous prescribed dose of MPH-IR, and pause of treatment on weekends. Results: From a total sample of 207 children, adolescents and adults (enrolled from the ADHD outpatient clinic at both Adult and Child and Adolescent Psychiatric Division of Hospital de Clínicas de Porto Alegre) we were able to re-contact 133 patients, where sixty-two patients were eligible to the clinical trial, and 47 completed the 08 weeks of treatment. There was no significant change in the total score of the SNAP-IV during the protocol – baseline, week 4 and 8 [F(1, 51.26)=0.012; p=0.913]. Overall, 46 (74.2%) patients had reported to be satisfied with the new treatment, and 16 (25.8%) were dissatisfied or withdrew from the protocol. In univariate analyses, only ethnicity (p=0.05) were associated with dissatisfaction. No significant change in the SERS score was found during the protocol [F(1, 111.49)=0.748; p=0.389]. Eleven adverse events occurring in at least 5% of the group in any assessment (baseline, 04 or 08 weeks) were observed according to SERS. One adult, with previous cardiovascular disease, presented a hemorrhagic cerebral vascular accident (CVA) after the forth week assessment, resulting in her obit. Conclusion: There is a scarcity of research assessing the switch from MPH-IR to different forms of MPH-ER, and none across the life cycle or in populations from developing countries. The 74.2% of satisfaction with the new treatment may reflect the convenience of the once-a-day dosing of the MPH SODAS™. No predictor of dissatisfaction/withdrawal from the trial was found. The number of adverse events reported during the protocol could be considered high, but this can be the result of the use of an appropriate assessment scale, rather than monitoring only by spontaneous report. It was not possible to find a direc relationship between the MPH SODAS™ and death from a CVA occurred in one of the subjects. However, the cardiovascular event found during the trial, suggest extreme caution when medicating patients with cardiovascular diseases as recently proposed by the FDA. Findings from this study suggest that MPH SODAS™ has similar efficacy and adverse event profile than MPH-IR.

L’Univers est dominé par une composante invisible appelée Matière Noire (MN), de nature inconnue mais dont les effets gravitationnels sur la matière visible sont clairement observés. Il a été proposé que la MN soit constituée de particules massives et interagissant faiblement avec la matière, permettant ainsi de concilier théorie, observations et simulations. L’annihilation de ces particules dans les régions où la MN est fortement concentrée pourrait produire des rayons γ de très haute énergie dont les signatures spectrales peuvent être détectées par le réseau de télescopes H.E.S.S. Un excès à ~3σ est observé dans la direction de la Galaxie Naine du Sagittaire, avec la méthode standard d’analyse ON-OFF. Plus de données sont nécessaires pour conclure quant à son origine. La seconde partie du travail concerne la recherche de raies spectrales en γ dans la région du Centre Galactique. Une méthode de Maximum de Vraisemblance Complète a été développée, étalonnée et appliquée à une fraction d’un ensemble de 20h de données prises en 2014. Aucun excès de γ n’étant observé, des limites sur la section efficace d’annihilation de la MN sont produites pour des masses de 100 GeV à 2 TeV, la sensibilité de H.E.S.S. à basse énergie étant obtenue par l’ajout d’un 5ème télescope depuis 2012. Ces limites complètent efficacement les précédents résultats de Fermi-LAT et H.E.S.S. D’autre part l’analyse finale devrait permettre d’exclure un potentiel signal à 130 GeV observé dans les données de Fermi-LAT en 2012 et ce avec plus de 95% CL, et de proposer les limites les plus solides à ce jour sur les modèles d’émission de raies spectrales en γ dans le domaine d’énergie couvert par H.E.S.S. / The Universe is full of gravitational evidence of a dominant invisible Dark Matter (DM) component at the Galactic and cosmological scales. Although its nature is still one of the major puzzles of the 21st Century, Weakly Interacting Massive Particles (WIMPs) are an excellent scenario for matching theoretical predictions with observations and simulations. In particular, their self-annihilations would give rise to characteristic spectral signatures in γ-rays, detectable at Very High Energies (VHE) with the H.E.S.S. telescope array in regions such as the Galactic Centre (GC) and Dwarf Spheroidal Galaxies (dSphs). The standard ON-OFF analysis method is applied in the observation of the Sagittarius dSph where a ~3σ hotspot is observed above 300 GeV, although more statistics is required to conclude on its potential DM origin. The second part of the work is focused on the search for monochromatic γ-ray line signatures in the GC region. A Full Likelihood method has been developed, calibrated with Monte-Carlo simulations and applied to a sub-sample of a 20h dataset acquired in 2014. No excess signal is found, thus leading to limits on the DM annihilation cross-section down to a 100 GeV mass range, the sensitivity at the lowest energies being achieved by the 5th H.E.S.S. telescope added in 2012. These limits efficiently fill the gap in mass between results from Fermi-LAT and the first phase of H.E.S.S. On the other side the analysis of the complete dataset is expected to exclude the 130 GeV line-like feature recently reported in the Fermi-LAT data, with more than 95% CL, and to provide the most constraining DM limits so far on γ-ray line emission in the VHE range.

In this dissertation, channel estimation and channel prediction are studied for wireless communication systems. Wireless communication for time-variant channels becomes more important by the fast development of intelligent transportation systems which motivates us to propose a reduced rank channel estimator for time-variant frequency-selective high-speed railway (HSR) systems and a reduced rank channel predictor for fast time-variant flat fading channels. Moreover, the potential availability of large bandwidth channels at mm-wave frequencies and the small wavelength of the mm-waves, offer the mm-wave massive multiple-input multiple-output (MIMO) communication as a promising technology for 5G cellular networks. The high fabrication cost and power consumption of the radio frequency (RF) units at mm-wave frequencies motivates us to propose a low-power hybrid channel estimator for mm-wave MIMO orthogonal frequency-division multiplexing (OFDM) systems. The work on HSR channel estimation takes advantage of the channel's restriction to low dimensional subspaces due to the time, frequency and spatial correlation of the channel and presents a low complexity linear minimum mean square error (LMMSE) estimator for MIMO-OFDM HSR channels. The channel estimator utilizes a four-dimensional (4D) basis expansion channel model obtained from band-limited generalized discrete prolate spheroidal (GDPS) sequences. Exploiting the channel's band-limitation property, the proposed channel estimator outperforms the conventional interpolation based least square (LS) and MMSE estimators in terms of estimation accuracy and computational complexity, respectively. Simulation results demonstrate the robust performance of the proposed estimator for different delay, Doppler and angular spreads. Channel state information (CSI) is required at the transmitter for improving the performance gain of the spatial multiplexing MIMO systems through linear precoding. In order to avoid the high data rate feedback lines, which are required in fast time-variant channels for updating the transmitter with the rapidly changing CSI, a subframe-wise channel tracking scheme is presented. The proposed channel predictor is based on an assumed DPS basis expansion model (DPS-BEM) for exploiting the variation of the channel coefficients inside each sub-frame and an autoregressive (AR) model of the basis coefficients over each transmitted frame. The proposed predictor properly exploits the channel's restriction to low dimensional subspaces for reducing the prediction error and the computational complexity. Simulation results demonstrate that the proposed channel predictor out-performs the DPS based minimum energy (ME) predictor for different ranges of normalized Doppler frequencies and has better performance than the conventional Wiener predictor for slower time-variant channels and almost the similar performance to it for very fast time-variant channels with the reduced amount of computational complexity. The work on the hybrid mm-wave channel estimator considers the sparse nature of the mm-wave channel in angular domain and leverages the compressed sensing (CS) tools for recovering the angular support of the MIMO-OFDM mm-wave channel. The angular channel is treated in a continuous framework which resolves the limited angular resolution of the discrete sparse channel models used in the previous CS based channel estimators. The power leakage problem is also addressed by modeling the continuous angular channel as a multi-band signal with the bandwidth of each sub-band being proportional to the amount of power leakage. The RF combiner is designed to be implemented using a network of low-power switches for antenna subset selection based on a multi-coset sampling pattern. Simulation results validate the effectiveness of the proposed hybrid channel estimator both in terms of the estimation accuracy and the RF power consumption. / Graduate

The thesis is concerned with relationships between progressive technological processes of spheroidal graphite cast iron’s production and their structural properties. The aim of the work is to explain causal relationship between parameters of the proposed manufacturing technology of the iron type given (involving selected variants of modification and inoculation of melt and the parameters of melt crystallization, solidification and cooling down in a mould), their structure and even chemical heterogeneity of elements in this structure. For close specification of presented relationships three-dimensional model of spheroidal graphite growth was used, which was developed at the Brno University of Technology, Faculty of Mechanical Engineering. Its usability in praxis has been verified on the basisis of the application of this model on experimentally acquired data. The U GRAFIT 20 model of the authors Stránský and Million counting segregation in the frame of eutectic cell has not still been used for prediction of segregation in real condition in greater extent. On the basis of the above mentioned model microsegregation within “on average” of the cell has been discovered during experimental melts. Microsegregation has been described by segregation and heterogeneity indexes. Calculated values of segregation and heterogeneity indexes have been compared with experimentally verified values. On the basis of comparison of calculated and measured values the possibility of further usage of the mentioned model in praxis has been explored.

Diffusion Tensor MRI can be used to depict the anisotropy of tissue. Translation of this technique to moving objects such as the beating heart has recently become feasible, but remains a challenging task, often leading to high noise levels and limited accuracy. Ultimately, knowledge of the 3D fibre architecture of the myocardium invivo should allow for a better understanding of the cardiac function both in healthy and pathological situations. The main goal of the work presented in this thesis is to overcome the difficulties that such technology presents, by introducing a combination of image processing and analysis approaches. In particular, the characteristic ellipsoidal shape of the left ventricular chamber is used to introduce a shape-based prolate spheroidal coordinate frame that allows for comprehensive, robust and dedicated analysis of diffusion tensor data within the myocardial wall. It is shown that the description of this information is more compact in this coordinate frame. Furthermore, it is demonstrated that the acquisition limitations can be overcome by introducing an approximation scheme based on this coordinate frame. These techniques are tested on ex-vivo datasets to assess their fidelity and sensitivity. Finally, these techniques are applied in-vivo on a group of healthy volunteers, where 2D DTI slices of the LV were acquired at end diastole and end systole, using cardiac dedicated diffusion MR acquisition. Results demonstrate the advantages of using curvilinear coordinates both for the analysis and the approximation of cardiac DTI information. Resulting in-vivo fibre architectures were found to agree with previously reported studies on ex-vivo specimens. The outcome of this work can open the door for clinical applications and cardiac electrophysiology modelling, and improve the understanding of the left ventricular structure and dynamics.

Les pompes sèches primaires dédiées aux procédés de fabrication en microélectronique sont soumises à des environnements très corrosifs de plus en plus oxydants et halogénés (Cl2, F2 et O2). Or pour des raisons mécaniques et économiques, les parties fonctionnelles des pompes sont usinées dans la fonte à graphite sphéroïdale EN-GJS-500-7. La fonte est alors protégée par un dépôt de nickel-phosphore (NiP) chimique. Cette thèse, reprend des études classiques sur la cinétique et le mécanisme de nickelage d'une part, et sur l'optimisation des propriétés mécaniques et la résistance à la corrosion des couches de NiP d'autre part. Cependant, le caractère innovant de ce travail repose sur la réalisation de couches NiP sur un substrat en fonte à graphite sphéroïdale.L'étude de la cinétique de nickelage et la caractérisation morphologique des revêtements en fonction du temps de dépôt a montré l'influence de la nature chimique du substrat. Les sphères de graphite affleurantes à la surface du substrat n'étant pas catalyseur du nickel chimique, provoque des défauts dans le revêtement, dommageables pour la conformité du dépôt. Il a été montré qu'une polarisation cathodique de la surface du substrat pouvait, dans les premiers instants du dépôt, amorcer le nickelage à l'aplomb des sphères de graphite.Une relation entre la microstructure des dépôts en fonction des traitements thermiques subis et des propriétés mécaniques des couches de NiP a été mise une évidence. Les dépôts NiP amorphes présentent une faible dureté et un comportement ductile tandis que les dépôts cristallisés possèdent une dureté élevée et un comportement fragile. Ces dépôts ont une bonne tenue à la corrosion en milieux halogéné lorsqu'ils sont intacts. Actuellement, au niveau industriel, les dépôts les plus fragiles sont choisis, bien qu'ils présentent une résistance à la corrosion plus faible : en effet, la durée de vie des pompes est alors supérieure car les effets de grippage sont atténués.Mots-clés : nickel chimique, résistance à la corrosion, fonte à graphite sphéroïdale, caractérisation physico-chimique, couches minces, durabilité mécanique / Primary dry pumps dedicated to manufacturing processes in microelectronics are subjected to highly corrosive environments that are increasingly oxidizing and halogenous (Cl2, F2 and O2). However, for mechanical and economic reasons, the functional parts of the pumps are machined in EN-GJS-500-7 spheroidal graphite cast iron. The cast iron is consequently protected by a nickel-phosphorus chemical deposit. This thesis is based on classical studies on the kinetics and the nickel-plating mechanism on the one hand, and on the optimization of the mechanical properties and corrosion resistance of the NiP layers on the other hand. The innovative nature of this work is based on the production of NiP layers on a spheroidal graphite cast iron substrate.The study of the kinetics of nickel-plating as well as the morphological characterization of coatings as a function of the deposit time showed the influence of the chemical nature of the substrate. The flush graphite spheres on the surface of the substrate being not a catalyst for the chemical nickel, they can cause defects in the coating and a loss of compliance. It has been shown that a cathodic polarization of the surface of the substrate, in the first moments of the deposit, could initiate the nickel-plating right on the graphite spheres.A relationship exists between the microstructure of the deposits as a function of the thermal treatments undergone and the mechanical properties of the NiP layers. The amorphous NiP deposits have a low hardness and a ductile behavior while crystallized deposits have a high hardness and a brittle behavior. These deposits have a good resistance to corrosion in halogenated environments when they are intact. Actually, at the industrial level, the most brittle deposits are chosen, although they have a lower corrosion résistance: indeed, the service life of the pumps is higher because the seizing effect are minimized.Keywords: electroless nickel, resistance to corrosion, spheroidal graphite cast iron, physicochemical characterization, thin layers, mechanical durability

Bei der Herstellung von dickwandigem GJS treten zahlreiche ungeklärte Effekte durch die sehr langsamen Abkühlungs- und Erstarrungsgeschwindigkeiten auf. Bisherige Untersuchungsmethoden ermöglichen keine definierte Temperaturführung analog zum realen Bauteil und benötigen trotzdem große Schmelzemengen und einen hohen Trennaufwand für die Probenherstellung. Das Ziel der Arbeit bestand in der Entwicklung einer Versuchsmethode zur experimentellen Simulation extrem langer Abkühl- und Erstarrungszeiten von GJS. Die Verwendung einer geeigneten Abdeckung der Schmelze zur Minimierung des Mg-Abbrandes und eines druckfesten Kaltwandofens inkl. dynamischer Temperatursteuerung ermöglichte reproduzierbare Versuche zur Einstellung verschiedener Gefügezustände durch Variation der Abkühlregime und des Impfzustandes. Es gelang, Chunkygrafit und Grafitflotation gezielt herzustellen und dadurch die Entstehungsmechanismen wissenschaftlich zu untersuchen. Ein Chunkygrafit-Index-Diagramm konnte erarbeitet werden.

<p><b>Part I: Micromechanics of dense suspensions</b></p><p>Particulate suspensions are ubiquitous in the industry & nature. Fresh concrete, uncured solid rocket fuel, & biomass slurries are typical industrial applications, while milk & blood are examples of naturally occurring suspensions. These suspensions exhibit many non-Newtonian properties like rate-dependent rheology & normal stresses. Other than volume fraction, particle material, inter-particle interactions determine the rheological behavior of suspension. The average inter-particle gaps between the neighboring particles decrease significantly as the suspension volume fraction approaches the maximum packing fraction in dense suspensions. So, in this regime, the short-ranged non-contact interactions are important. In addition, the particles come into contact due to asperities on their surfaces. The surface asperities are present even in the case of so-called smooth particles, as particles in real suspensions are not perfectly smooth. Hence, contact forces become one of the essential factors to determine the rheology of suspensions.</p><p> </p><p>Part I of this thesis investigates the effects of microscopic inter-particle interactions on the rheological properties of dense suspensions of non-Brownian particles by employing discrete particle simulations. We show that increasing the roughness size results in a rise in the viscosity & normal stress difference in the suspensions. Furthermore, we observe that the jamming volume fraction decreases with the particle roughness. Consequently, for suspensions close to jamming, increasing the asperity size reduces the critical shear rate for shear thickening (ST) transition, resulting in an early onset of discontinuous ST (DST, a sudden jump in the suspension viscosity) in terms of volume fraction, & enhances the strength of the ST effect. These findings are in excellent agreement with the recent experimental measurements & provide a deeper understanding of the experimental findings. Finally, we propose a constitutive model to quantify the effect of the roughness size on the rheology of dense ST suspensions to span the entire phase-plane. Thus, the constitutive model and the experimentally validated numerical framework proposed can guide experiments, where the particle surface roughness is tuned for manipulating the dense suspension rheology according to different applications. </p><p> </p><p>A typical dense non-Brownian particulate suspension exhibits shear thinning (decreasing viscosity) at a low shear rate followed by a Newtonian plateau (constant viscosity) at an intermediate shear rate values which transition to ST (increasing viscosity) beyond a critical shear rate value and finally, undergoes a second shear-thinning transition at an extremely high shear rate values. This part unifies & quantitatively reproduces all the disparate rate-dependent regimes & the corresponding transitions for a dense non-Brownian suspension with increasing shear rate. The inclusion of traditional hydrodynamic interactions, attractive/repulsive DLVO (Derjaguin and Landau, Verwey and Overbeek), contact interactions, & constant friction reproduce the initial thinning as well as the ST transition. However, to quantitatively capture the intermediate Newtonian plateau and the second thinning, an additional interaction of non-DLVO origin & a decreasing coefficient of friction, respectively, are essential; thus, providing the first explanation for the presence these regimes. Expressions utilized for various interactions and friction are determined from experimental measurements, resulting in an excellent quantitative agreement with previous experiments. </p><p><br></p><p><b>Part II: Motion in a stratified fluid</b></p><p>Density variations due to temperature or salinity greatly influence the dynamics of objects like particles, drops, and microorganisms in oceans. Density stratification hampers the vertical flow & substantially affects the sedimentation of an isolated object, the hydrodynamic interactions between a pair, and the collective behavior of suspensions in various ways depending on the relative magnitude of stratification inertia (advection), and viscous (diffusion) effects. This part investigates these effects and elicits the hydrodynamic mechanisms behind some commonly observed fluid-particle transport phenomena in oceans, like aggregation in horizontal layers. The physical understanding can help us better model these phenomena and, hence, predict their geophysical, engineering, ecological, and environmental implications. </p><p><br></p><p>We investigate the self-propulsion of an inertial swimmer in a linear density stratified fluid using the archetypal squirmer model, which self-propels by generating tangential surface waves. We quantify swimming speeds for pushers (propelled from the rear) and pullers (propelled from the front) by direct numerical solution. We find that increasing stratification reduces the swimming speeds of swimmers relative to their speeds in a homogeneous fluid while reducing their swimming efficiency. The increase in the buoyancy force experienced by these squirmers due to the trapping of lighter fluid in their respective recirculatory regions as they move in the heavier fluid is one of the reasons for this reduction. Stratification also stabilizes the flow around a puller, keeping it axisymmetric even at high inertia, thus leading to otherwise absent stability in a homogeneous fluid. On the contrary, a strong stratification leads to instability in the motion of pushers by making the flow around them unsteady 3D, which is otherwise steady axisymmetric in a homogeneous fluid. Data for the mixing efficiency generated by individual squirmers explain the trends observed in the mixing produced by a swarm of squirmers. </p><p><br></p><p>In addition, the ubiquitous vertical density stratification in aquatic environments significantly alters the swimmer interactions affecting their collective motion &consequently ecological and environmental impact. To this end, we numerically investigate the interactions between a pair of model swimming organisms with finite inertia in a linear density stratified fluid. Depending on the squirmer inertia and stratification, we observe that the squirmer interactions can be categorized as i) pullers getting trapped in circular loops, ii) pullers escaping each other with separating angle decreasing with increasing stratification, iii) pushers sticking to each other after the collision and deflecting away from the collision plane, iv) pushers escaping with an angle of separation increasing with stratification. Stratification also increases the contact time for squirmer pairs. The results presented can help understand the mechanisms behind the accumulation of planktonic organisms in horizontal layers in a stratified environment like oceans and lakes. </p><p><br></p><p>Much work has been done to understand the settling dynamics of spherical particles in a homogeneous and stratified fluid. However, the effects of shape anisotropy on the settling dynamics in a stratified fluid are not entirely understood. To this end, we perform numerical simulations for settling oblate and prolate spheroids in a stratified fluid. We find that both the oblate and prolate spheroids reorient to the edge-wise and partially edge-wise orientations, respectively, as they settle in a stratified fluid completely different from the steady-state broad-side on orientation observed in a homogeneous fluid. We observe that reorientation instabilities emerge when the velocity magnitude of the spheroids falls below a particular threshold. We also report the enhancement of the drag on the particle from stratification. The torque due to buoyancy effects tries to orient the spheroid in an edge-wise orientation, while the hydrodynamic torque tries to orient it to a broad-side orientation. The buoyancy torque dominates below the velocity threshold, resulting in reorientation instability.<br></p>

This work is focused on segregation processes in the matrix of spheroidal graphite cast iron with different silicon and nickel content during heat treatment. The aim of this work is to trace the redistribution of the elements of interest during homogenization annealing with different dwell time by comparison of the effective distribution coefficients. Comparison of some specific properties and description of structure development of spheroidal graphite cast iron matrix from initial state to the state after ferritization and homogenization annealing is included in this work.