O treinamento resistido intervalado de alta intensidade (high intensity interval resistance training-HIIRT) tem se tornado cada vez mais popular nos últimos anos poispromoveresultados positivos com curtas sessões de treinamento. No entanto, sua alta intensidade pode causar efeitos adversos. O objetivo deste estudo foi avaliar se uma sessão de HIIRT causa dano muscular agudo e alterações nos biomarcadores de lesão renal. Cinquenta e oito voluntários saudáveis, divididos igualmente entre homens e mulheres com 24 anos de idade (mediana), participaram deste estudo. Nenhum deles usou suplementos dietéticos ou medicamentos. Eles foram submetidos a cinco minutos de aquecimento seguido de quatro minutos de HIIRT. Uma escala numérica de Borg para dor (CR10P), amostras de sangue e urina foram coletadas antes (basal), 2 e 24h após a sessão HIIRT. As amostras de sangue foram analisadas e dosadocreatinina sérica (CrS),lipocalina associada a gelatinase de neutrófilos (NGALS), creatinofosfoquinase (CPK) e mioglobina (Mio). As amostras urinárias foram analisadas e dosadoscreatinina (CrU),lipocalina associada a gelatinase de neutrófilos (NGALU), interleucina 18 (IL-18), calbindina, microalbuminúria (?albumina), trefoil factor-3(TFF3) e beta-2microglobulina (ß2M). O CR10 e CPK tiveramum aumento significativo e crescente após2 e 24h. Mioaumentou significativamente em 2h e continuouelevadaapós24h. CrSaumentou significativamente após24h e em três homens,o aumento atingiu os critérios para o diagnóstico de injúria renal aguda (IRA). Todos os biomarcadores urinários aumentaram significativamente 2 horas após o exercício e retornaram aos valores basais24h após HIIRT. Concluindo, uma única sessão de HIIRT em indivíduos jovens e saudáveis causou elevações precocese significativas em CPK, mioglobina, CrS,microalbuminúria e biomarcadores urinários, indicando lesão tubularrenal, sugerindo a ocorrência de rabdomiólise e danos funcionais eestruturais aos rins / High intensity interval resistance training (HIIRT) emerged as one of the fastest growing exercise programs in recent years because provides positive results with short training sessions. However, its high intensity might cause adverse effects. The aim of this study was to evaluate if a session of HIIRT causes acute muscle damage and changes in kidney injury biomarkers. Fifty-eight healthy volunteers, divided equally among men and women (median age 24 years), participated in this study. None of them used dietary supplements or medications. They were submitted to five minutes of warm-up followed by four minutes of HIIRT. A Borg CR10 Scale for pain (CR10P), and blood and urinary samples were collected before (baseline), 2 and 24h after HIIRT session. Blood samples were analyzed for serum creatinine (SCr), neutrophil gelatinase-associated lipocalin (SNGAL), creatine kinase(CK) and myoglobin (Myo). Urinary samples were assessed for creatinine (UCr), neutrophil gelatinase-associated lipocalin (UNGAL), interleukin 18 (IL-18), calbindin, microalbuminuria (ualbumin), trefoil factor-3 (TFF3) and beta-2 microglobulin (beta2M). CR10 had a significantly and crescent increase on 2 and 24h. CK increased significantly on 2h and further in 24h. Myo increased significantly on 2h and stayed elevated at 24h. SCr increased significantly on 24h and inthree men the increase met criteria for acute kidney injury diagnosis. All the other serum and urinary kidney injury biomarkers increased significantly at 2 hours and returned to basal values at 24h after HIIRT. In conclusion, a single session of HIIRT inyoung, healthy individuals caused early and significant elevations in CK, myoglobin, SCr, microalbuminuria and urinary biomarkers indicative of kidney tubular injury, suggesting the occurrence of rhabdomyolysis and functional and structural kidney damage

A principal reação de derivatização da quitina é a hidrólise dos grupos acetamido, que gera o polímero conhecido como quitosana. O foco do presente estudo é desenvolver um processo eficiente, reprodutivo e versátil para produção de quitosanas com características controladas. Nesse sentido, o processo de desacetilação de quitina assistida por irradiação do ultrassom de alta intensidade, denominado processo DAIUS, foi estudado. Para o desenvolvimento do estudo proposto, as seguintes etapas foram realizadas: i) extração, fracionamento e caracterização de beta-quitina extraída de gládios de lulas; ii) estudo quimiométrico visando determinar as variáveis mais importantes do processo DAIUS; iii) estudo quimiométrico visando a otimização do processo DAIUS empregando gráficos de superfícies de resposta e iv) estudo cinético da desacetilação de beta-quitina via processo DAIUS. A caracterização das quitosanas, obtidas pelo processo DAIUS com o auxílio do planejamento fatorial de experimentos revelou que a intensidade da irradiação de ultrassom é a variável menos importante durante a desacetilação da beta-quitina, e que a temperatura e o tempo de reação são as variáveis que mais afetam a despolimerização da beta-quitina. Desse estudo resultaram quitosanas com elevados <span style=\"text-decoration: overline\">GD (92%) e <span style=\"text-decoration: overline\">Mv (5,42x105g/mol), enquanto o parâmetro de acetilação (PA) apresentou valores próximos de 1,0, que corresponde ao padrão randômico ideal de distribuição de unidades GlcN e GlcNAc, sugerindo que o processo DAIUS ocorre homogeneamente. A análise dos gráficos de superfícies de resposta permitiu observar que o aumento da temperatura e do tempo de sonicação gera quitosanas mais desacetiladas, porém com menores massas molares. Esta análise também permitiu avaliar os efeitos do processo DAIUS sobre <span style=\"text-decoration: overline\">GD, <span style=\"text-decoration: overline\">Mv e PA, sendo que nesse estudo quitosanas com elevada <span style=\"text-decoration: overline\">Mv (9,83x105g/mol) foram obtidas, porém o aumento da temperatura e do tempo de sonicação resultou em quitosanas mais despolimerizadas, e também mais desacetiladas. A seleção das principais variáveis do processo DAIUS, temperatura de reação e do tempo de sonicação, permitiu uma melhor compreensão da variação do <span style=\"text-decoration: overline\">GD e da <span style=\"text-decoration: overline\">Mv, e permitiu a obtenção de quitosanas que apresentaram valores de PA&asymp;1,0, correspondente ao padrão randômico ideal de distribuição de unidades GlcN e GlcNAc. O estudo da cinética da desacetilação da beta-quitina via processo DAIUS revelou a ocorrência de duas etapas bem distintas quantos às suas velocidades, sendo a primeira, atuante nos primeiros 20 minutos, mais rápida (k=29,4 min-1 103) quando comparada com a segunda etapa (k=7,6 min-1 103). As quitosanas geradas no desenvolvimento do estudo cinético do processo DAIUS foram analisadas por difração de raios X, revelando que durante o processo DAIUS ocorre perda de água do retículo cristalino da beta-quitina, fato atribuído à cavitação gerada pela irradiação de ultrassom de alta intensidade. Assim, é proposto que o fenômeno da cavitação, que resulta em importantes alterações morfológicas, reduzindo as dimensões médias das partículas e aumentando sua rugosidade e uniformidade, também atue no interior do retículo cristalino da beta-quitina, resultando na expulsão de moléculas de água e facilitando o acesso do hidróxido de sódio aos grupamentos acetamido da beta-quitina mesmo nos domínios cristalinos. A utilização do ultrassom de alta intensidade na desacetilação de beta-quitina coloca em destaque a obtenção de quitosanas com características controladas. / The main reaction of chitin is the hydrolysis of its acetamido groups, which generates a polymer known as chitosan. The focus of the present study is the development of an efficient, reproductive and versatile process for chitosan production with controlled characteristics. In this sense, the chitin deacetylation assisted by high intensity ultrasound irradiation, called USAD process, was studied. The development of the proposed study was carried out in four steps: i) the extraction, fractionation and characterization of beta-chitin, extracted from squid pens; ii) the chemometric approach, aiming to determine the most important variables of the USAD process; iii) the chemometric approach aiming to the USAD process optimization, employing response surface and iv) the deacetylation kinetics studies of beta-chitin via USAD process. The characterization of the chitosans obtained by the USAD process, supported by factorial design, showed that the intensity of the ultrasound irradiation is the least important variable in the beta-chitin deacetylation, and the temperature and reaction time are the variables that most affect the beta-chitin depolymerization. From this study, chitosans with high <span style=\"text-decoration: overline\">DD (92%) and <span style=\"text-decoration: overline\">Mv (5.42 x105g/mol) were produced, with acetylation parameter (AP) values close to 1.0, which corresponds to an ideal random pattern of distribution of GlcNAc and GlcN units, suggesting that the USAD process occurs homogeneously. The analysis of response surfaces allowed to observe that the increase of temperature and sonication time generates more deacetylated chitosans, but with lower average molecular weights. This analysis also allowed us to evaluate the effects of USAD process in <span style=\"text-decoration: overline\">DD, <span style=\"text-decoration: overline\">Mv, and AP variations: chitosans with high <span style=\"text-decoration: overline\">Mv (9.83x105g/mol) were obtained, but the increase of temperature and sonication time resulted in more degraded and more deacetylated chitosans. The selection of the main USAD process variables, temperature and sonication time, allowed a better understanding of <span style=\"text-decoration: overline\">DD and <span style=\"text-decoration: overline\">Mv variation, and allowed to obtain chitosan with PA&asymp;1.0, which corresponds to an ideal random pattern of distribution of GlcNAc and GlcN units. The study of beta-chitin deacetylation kinetics via USAD process revealed the occurrence of two stages: the first step, active in the first 20 minutes, is faster (k = 29.4 min-1 103) when compared with the second one (k = 7.6 min-1 103). The chitosans generated in the kinetic study of the USAD process were analyzed by X-ray diffraction, which revealed some water loss in the crystalline structure during the USAD process, which is attributed to the cavitation generated by irradiation of high intensity ultrasound. Thus, it is suggested that the phenomenon of cavitation, which results in significant morphological changes by reducing average particle size and increase uniformity and roughness, also act within the crystalline structure of beta-chitin, resulting in the expulsion of water molecules and facilitating the access of sodium hydroxide to beta-chitin acetamido groups even in the crystalline domains. The use of high intensity ultrasound in deacetylation of beta-chitin highlight the production of chitosans with controlled characteristics.

Submitted by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-08-08T14:11:40Z No. of bitstreams: 1 ArilsonFernandesMendoncadeSousaTese2018.pdf: 5768876 bytes, checksum: 66d7e7ce78b9d2a4b54e615ac9d3282d (MD5) / Approved for entry into archive by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-08-08T14:11:52Z (GMT) No. of bitstreams: 1 ArilsonFernandesMendoncadeSousaTese2018.pdf: 5768876 bytes, checksum: 66d7e7ce78b9d2a4b54e615ac9d3282d (MD5) / Made available in DSpace on 2018-08-08T14:11:52Z (GMT). No. of bitstreams: 1 ArilsonFernandesMendoncadeSousaTese2018.pdf: 5768876 bytes, checksum: 66d7e7ce78b9d2a4b54e615ac9d3282d (MD5) Previous issue date: 2018-05-25 / Only two weeks of sprint interval training (SIT) has been shown to be associated with positive changes in aerobic capacity and cardiac autonomic control. Both aerobic capacity and autonomic control have been shown to be positively associated with improved attention. However, to date, the relationship between this type of training and attention has not been investigated yet. The aim of the present study was to investigate the influence of two weeks of SIT on aerobic capacity, cardiac autonomic control and attention components in healthy university students; Also, to verify if the training fidelity would influence these adaptations. One hundred and nine participants were divided into experimental (EG) and control (CG) groups. EG performed a SIT program consisting of 6 sessions of maximal 4 × 30 s all-out efforts on a cycle ergometer, interspersed with active 4-minute rests. The criterion for fidelity was to reach> 90% of the estimated maximum heart rate (HR) during sprint sessions. After analysis, EG was divided into fidelity groups HIGH (n = 26) and LOW (n = 46), respectively. The attention components were evaluated through the Attention Network Test (ANT). The aerobic capacity (VO2max) was estimated according to Astrand's nomogram while the sum of the skinfolds: pectoral, triceps, subscapular, medial axillary, abdomen, suprailiac and thigh was verified. Autonomic HR control was assessed by HR variability (HRV) and HR complexity at rest and during ANT, before and after six sessions of SIT. Both HIGH and LOW significantly increased aerobic capacity, vagal modulation before and during ANT and executive control, and decreased body fat after SIT (p <0.05). However, only HIGH participants showed an increase in HR complexity and accuracy in ANT responses when compared to LOW (p <0.05). Two weeks of SIT improved executive control, body fat, aerobic capacity and autonomic control in university students, with better results reported for the HIGH group. / Apenas duas semanas de treinamento intervalado de esforços supra máximos (TIsm) tem mostrado estar associado com modificações positivas na capacidade aeróbia e controle autonômico cardíaco. Tanto a capacidade aeróbia, como o controlo autonômico demonstram estar associados positivamente com melhoria da atenção. Entretanto, até o presente momento a relação entre este tipo de treinamento e atenção não foi investigada. O objetivo do presente estudo foi investigar a influência de um programa de TIsm na capacidade aeróbia, controle autonômico cardíaco e componentes da atenção em jovens universitários saudáveis; ainda, verificar se a fidelidade do treinamento influenciaria essas adaptações. Cento e nove participantes foram divididos em grupo experimental (GE) e controle (GC). O GE realizou um programa TIsm que consistiu em 6 sessões de TIsm de 4 × 30 s em um cicloergômetro, intercaladas com descansos ativos de 4 min. O critério para fidelidade foi atingir> 90% da frequência cardíaca máxima estimada (FC) durante as sessões de TIsm. Após as análises, o GE foi dividido em grupos de fidelidade alta, GEA (n = 26) e baixa, GEB (n = 46), respectivamente. Os componentes da atenção foram avaliados por meio do Teste de Rede de Atenção (ANT). A capacidade aeróbia (VO2max) foi estimada segundo o nomograma de Astrand enquanto o somatório de dobras cutâneas: peitoral, tríceps, subescapular, axilar média, abdômen, supra-ilíaca e coxa foi realizada. O controle autonômico da FC foi avaliado por meio da VFC e complexidade da FC em repouso e durante o ANT, antes e depois de seis sessões de TIsm. Ambos GEA e GEB aumentaram significativamente a capacidade aeróbia, modulação vagal antes e durante a realização do ANT e o controle executivo e diminuição da gordura corporal após o TIsm (p <0,05). No entanto, apenas os participantes do GEA apresentaram um aumento na complexidade da FC e acurácia nas respostas do ANT quando comparados ao GEB (p <0,05). Duas semanas de TIsm melhoraram o controle executivo, a gordura corporal, a capacidade aeróbia e o controle autonômico em estudantes universitários, com melhores resultados relatados para o grupo com GEA fidelidade.

L'interaction d'impulsions lasers brèves et intenses avec un plasma est une source intéressante d'ions énergétiques. Les travaux effectués au cours de cette thèse s'articulent autour de deux grandes thématiques : la production de protons par laser, et leur utilisation pour le chauffage isochore, avec, pour principal outil d'étude, la simulation à l'aide de codes numériques (cinétique particulaire et hydrodynamique). Dans un premier temps, nous avons étudié le comportement de l'énergie cinétique maximale des protons qu'il est possible d'accélérer avec le mécanisme du Target Normal Sheath Acceleration (TNSA), en régime sub-ps, en fonction de différents paramètres, notamment de la durée d'impulsion laser. Nous avons montré que l'allongement de la durée d'impulsion, à énergie laser constante, est responsable du préchauffage et de la détente du plasma avant l'arrivé du pic d'intensité. Les gradients de densité ainsi produits (face avant et face arrière) peuvent favoriser, ou au contraire pénaliser, le gain en énergie cinétique des protons. Les résultats obtenus ont servi à l'interprétation d'une étude expérimentale réalisée au Laboratoire d'Optique Appliquée. Nos efforts se sont ensuite concentrés sur l'élaboration d'un modèle semi-analytique rendant compte de l'énergie cinétique maximale des protons accélérés par le biais du TNSA. Ce modèle permet de retrouver l'ordre de grandeur des intensités nécessaires, de l'ordre de 6x1021 W/cm², pour atteindre des énergies de proton supérieures à 150 MeV avec des impulsions laser de quelques joules et plusieurs dizaines de fs. Dans la dernière partie de cette thèse, nous nous sommes intéressés à l'utilisation de ces faisceaux de protons pour le chauffage isochore. Nous avons caractérisé, dans un premier temps, les fonctions de distribution produites par des cibles composées d'un substrat lourd (A >> 1) sur la face arrière duquel est déposé un plot d'hydrogène (schéma d'Esirkepov). Ensuite, à partir de simulations hydrodynamiques, nous avons étudié le temps caractéristique de détente de la cible chauffée en modifiant des paramètres tels que la distance à la source de protons, l'intensité et la tache focale du laser, et la densité surfacique du plot. Nous avons enfin étendu cette étude aux cibles cylindriques et nous avons montré qu'il est possible de réduire les effets liés à la divergence naturelle du faisceau de protons et ainsi d'obtenir des températures plus élevées. / The interaction of ultra-high intensity, ultra-short laser pulses with matter is an interesting source of energetic ions. During this work, we studied the production of energetic protons and their application to isochoric heating using kinetics and hydrodynamics code. We first considered the behavior of the maximum proton kinetic energy with the Target Normal Sheath Acceleration (TNSA) mechanism, in the sub-ps interaction regime, as a function of different parameters, especially the laser pulse duration. We showed that stretching the pulse duration, with a constant laser energy, led to the preheating and the expansion of the plasma slab. This expansion can be beneficial or detrimental regarding the maximum proton kinetic energy. The results we obtained helped to explain an experimental study carried out at the Laboratoire d'Optique Appliquée. We then developed a semi-analytical model trying to describe the maximum proton kinetic energy that can be produced in the TNSA regime. The results we obtained can retrieve the minimum intensity, of the order of 6x1021 W/cm², that is required to reach proton energies of 150 MeV with femtosecond, few joules laser pulses. As a final step, we were interested in the use of these proton beams for isochoric heating. We first characterized the proton distribution function produced by targets consisting in an heavy substrate with an hydrogen is deposited at the rear side. By the mean of hydrodynamics simulations, we studied the characteristic expansion time of the heated target by varying several parameters such as the heated sample distance from the proton source, the intensity and focal spot size of the laser, and the areal density of the dot. Finally, we extended the previous study to cylindrical targets and we demonstrated that it is possible to counterbalance the natural divergence of the proton beam and hence, to reach higher temperatures.

Cardiovascular diseases (CVD) are the leading cause of death, and the underlying atherosclerotic process has its origin in youth. Physical activity lowers future CVD risk, however few adolescents achieve the recommended minimum amount of daily activity and interventions fail to meaningfully increase activity levels in this group. It is therefore essential to identify how small volumes of exercise can be optimised for the primary prevention of CVD. The purpose of this thesis is to identify the influence of exercise intensity on vascular health outcomes in adolescents, and to assess the efficacy of 2 weeks of low volume, high-intensity interval training on CVD risk factors in this population. Chapter 4 demonstrates that a single bout of high-intensity interval exercise (HIIE) performed one hour before a high fat meal elicits comparable reductions in postprandial lipaemia as a work-matched bout of moderate-intensity exercise (MIE) in girls. However, neither exercise attenuated postprandial lipaemia in the boys. Additionally, HIIE elicited a superior increase in postprandial fat oxidation and decrease in blood pressure, and this was sex independent. These findings are furthered in Chapter 5, which identified that accumulating HIIE, but not MIE, favourably modulates glycaemic control, postprandial blood pressure and fat oxidation in adolescents irrespective of sex. A high fat meal was included in Chapter 6 in order to impair vascular function via oxidative stress. Postprandial vascular function was preserved following MIE, but improved after HIIE, and these changes were not related to changes in postprandial lipaemia or total antioxidant status. Chapter 7 addressed the time course of the changes in vascular function post exercise, and identified that HIIE promotes superior changes in vascular function than MIE. Finally, Chapter 8 identified that 2 weeks of high-intensity interval training improved novel (endothelial function and heart rate variability), but not traditional CVD factors in adolescent boys and girls. However, most of these favourable changes were lost 3 days after training cessation. Thus, this thesis demonstrates that vascular health outcomes are positively associated with exercise intensity. Given that HIIE was perceived to be more enjoyable than MIE in Chapters 4, 6 and 7, performing HIIE appears to be an effectual and feasible alternative to MIE for the primary prevention of CVD.

L’exercice fractionné de haute intensité (HIIT) et continu d’intensité modéré (MOD) représentent les 2 grandes modalités d'endurance. Cependant, leur impact spécifique sur la performance physique et la plasticité cérébrale et musculaire reste controversé du fait de la diversité des protocoles d’exercice proposés chez les sédentaires. Notre 1er axe dégage chez des rats sains l’effet de ces 2 modalités sur la performance physique, la plasticité musculaire et cérébrale sur 8 semaines d’entrainement standardisée dont l'intensité est basées sur le seuil lactique. Nos résultats montrent des gains de performance d’endurance plus rapides et importants suite aux HIIT. La neuroplasticité serait stimulée par les HIIT uniquement et la plasticité musculaire semble spécifique à chacune. L’engouement pour les HIIT se répercute chez les patients subissant un accident vasculaire cérébral où l’efficacité des méthodes d’endurance n’est pas clairement justifiées. Une étude antérieure a montré l’intérêt majeur des HIIT dans la phase aiguë de la pathologie malgré une récupération sensorimotrice incomplète. D’où l’intérêt d’approfondir dans notre second axe l’effet des différentes formes de HIIT (longs et courts) dans la récupération. Nos résultats montrent principalement que ces deux formes de HIIT améliorent la capacité d’endurance et la force de la patte antérieure lésée avec une précocité pour les HIIT longs. Les deux formes de HIIT semblent induire une angiogenèse cérébrale. Néanmoins, ils n’améliorent pas les fonctions sensorimotrices et cognitives. Ainsi, il est nécessaire d’approfondir les répercussions de ces deux entrainements HIIT dans la plasticité musculaire et cérébrale. / Endurance exercise is essential for different reasons in athlete and also in aging and pathological people. Two training modalities were found: high intensity interval training (HIIT) and moderate intensity aerobic training (MOD). However, the specific outcomes of these modalities on physical performance and cerebral and muscular plasticity are controversial because many exercise protocols exist. The 1st study explore the impact of these 2 training on endurance and functional capacity and also on muscular and cerebral molecular modifications throughout 8 weeks in healthy rats. HIIT and MOD programs are work-matched and training intensity are determined thanks to the lactate threshold. Our results show a superior and fast effect on endurance capacity after HIIT compared to MOD. Hippocampal plasticity is stimulated only after HIIT and muscular modifications appear to be specific to each modality. A great interest of HIIT is found in stroke patients for whom evidence of endurance modalities efficiency is still missing. A previous study has shown a beneficial effect of HIIT in the acute phase of stroke despite incomplete sensorimotor recuperation. Hence, the interest to deepen in second part of this manuscript the impact of two HIIT modalities (short and long) in recovery optimisation. Our results show that 2 HIIT strongly improve endurance performance and strength of injured paw with a fast effect for long HIIT. The 2 modalities seem to induce cerebral angiogenesis. However, these 2 training do not increase sensorimotor and cognitive functions. In perspective, it appears necessary to develop muscular and cerebral outcomes induced by these 2 HIIT modalities.

This thesis examined the translocation of fatty acid (FA) transport proteins to the plasma membrane (PM) in human and rat skeletal muscle during moderate intensity exercise. The responses to the post-exercise period and to acute moderate intensity exercise after 6 weeks of high intensity interval training (HIIT) were also examined in humans. The overall hypotheses were that 1) FAT/CD36 and FABPpm would translocate to the PM in human skeletal muscle during 120 min of moderate intensity exercise, 2) FAT/CD36 and FABPpm would translocate to the PM in rat skeletal muscle during 120 min of moderate intensity exercise and this would correlate to an increase in palmitate uptake, 3) FAT/CD36 and FABPpm would translocate to the PM during 120 min of moderate intensity exercise, but return to basal levels by 45 min post-exercise, 4) six weeks of HIIT would increase PM content of FABPpm but not FAT/CD36 in resting skeletal muscle, 5) six weeks of HIIT would cause a further increase in the translocation of FAT/CD36 and FABPpm to the PM during moderate intensity exercise and this would correspond to an increase in whole body fat oxidation compared to exercise pre-training, and 6) six weeks of HIIT would increase whole muscle content of FATP1 and FATP4. In human skeletal muscle, PM FAT/CD36 and FABPpm increased 75% and 20% respectively after 120 min of cycling at ~60% VO2 peak which corresponded to a 110% increase in whole body fat oxidation. In rat skeletal muscle, PM FAT/CD36 and FABPpm increased 20% and 30% respectively, which correlated to a 30% increase in palmitate uptake following 120 min of treadmill running at ~65% VO2 peak. The PM content of FAT/CD36 increased further to 120% of resting values by 45 min of post-exercise following 120 min of cycling at ~60% VO2peak, which correlated with a heavy reliance on fat as a fuel during the post-exercise period. FABPpm returned to resting levels of PM content by 15 min post-exercise. After 6 wk of HIIT, whole muscle FAT/CD36 (50%), FABPpm (21%) and FATP4 (25%) were increased in human skeletal muscle, while FATP1 remained unchanged. There were no changes in PM content of FAT/CD36 or FABPpm at rest following training. FAT/CD36 and FABPpm were also measured before and after 120 min of cycling at ~60% of pre-trainingVO2 peak following training, but no differences in the magnitude of the PM content increases were seen compared to pre-training, despite a 27% increase in fat oxidation. These studies demonstrate that FA transport proteins translocate to the PM during moderate intensity exercise, which correlates with increased FA uptake and whole body fat oxidation. This relationship does not appear to hold during the post-exercise period, as further increases in the PM content of FAT/CD36 does not correspond with the decrease in fat oxidation. The PM content of FAT/CD36 and FABPpm were not increased at rest following training, and there was no effect of training on the translocation of FAT/CD36 or FABPpm to the PM during moderate intensity exercise at the same absolute power output, however there may be a further increase at a relative power output. / Natural Sciences and Engineering Research Council, Canadian Institute of Health Research, Ontario Graduate Scholarship

The Apollon-10 PW laser chain is a large-scale project aimed at delivering 10 PW pulses to reach intensities of 10^22 W/cm^2. State of the art, high intensity lasers based solely on chirped pulse amplification (CPA) and titanium sapphire (Ti:Sa) crystals are limited to peak powers reaching 1.3 PW with 30-fs pulses as a result of gain narrowing in the amplifiers. To access the multipetawatt regime, gain narrowing can be suppressed with an alternative amplification technique called optical parametric chirped pulse amplification (OPCPA), offering a broader gain bandwidth and pulse durations as short as 10 fs. The Apollon-10 PW laser will exploit a hybrid OPCPA-Ti:Sa-CPA strategy to attain 10-PW pulses with 150 J and 15 fs. It will have two high-gain, low-energy amplification stages (10 fs ,100 mJ range) based on OPCPA in the picosecond and nanosecond timescale and afterwards, and will use Ti:Sa for power amplification to the 100-Joule level.Work in this thesis involves the progression of the development on the Apollon-10 PW front end and is focused on the development of a high contrast, ultrashort seed source supporting 10-fs pulses, stretching these pulses prior to OPCPA and the implementation of the picosecond OPCPA stage with a target of achieving 10-mJ pulses and maintaining its bandwidth. To achieve the final goal of 15-fs, 150-J pulses, the seed source must have a bandwidth supporting 10-fs and a temporal contrast of at least 10^10. Thus from an initial commercial Ti:Sa source delivering 25-fs pulses with a contrast of 10^8, spectral broadening via self-phase modulation and contrast enhancement with cross polarized (XPW) generation was performed. Subsequently, the seed pulses were stretched to a few picoseconds to match the pump for picosecond OPCPA. Strecher designs using an acousto-optic programmable dispersive filter (dazzler) for phase control in this purpose are studied. A compact and straightforward compressor using BK7 glass is used and an associated compressor for pulse monitoring was also studied. Lastly, the picosecond OPCPA stage was implemented in single and dual stage configurations.

Free-electron lasers provide high intensity pulses with femtosecond duration and are ideal tools in the investigation of ultrafast processes in materials. Illumination of any material with such pulses creates extreme conditions that drive the sample far from equilibrium and rapidly convert it into high temperature plasma. The dynamics of this transition is not fully understood and the main goal of this thesis is to further our knowledge in this area. We exposed a variety of materials to X-ray pulses of intensities from 1013 to above 1017 W/cm2. We found that the temporal evolution of the resulting plasmas depends strongly on the wavelength and pulse intensity, as well as on material related parameters, such as size, density, and composition. In experiments on atomic and molecular clusters, we find that cluster size and sample composition influence the destruction pathway. In small clusters a rapid Coulomb explosion takes place while larger clusters undergo a hydrodynamic expansion. We have characterized this transition in methane clusters and discovered a strong isotope effect that promotes the acceleration of deuterium ions relative to hydrogen. Our results also show that ions escaping from exploding xenon clusters are accelerated to several keV energies. Virus particles represent a transition between hetero-nuclear clusters and complex biological materials. We injected single mimivirus particles into the pulse train of an X-ray laser, and recorded coherent diffraction images simultaneously with the fragmentation patterns of the individual particles. We used these results to test theoretical damage models. Correlation between the diffraction patterns and sample fragmentation shows how damage develops after the intense pulse has left the sample. Moving from sub-micron objects to bulk materials gave rise to new phenomena. Our experiments with high-intensity X-ray pulses on bulk, metallic samples show the development of a transient X-ray transparency. We also describe the saturation of photoabsorption during ablation of vanadium and niobium samples. Photon science with extremely strong X-ray pulses is in its infancy today and will require much more effort to gain more knowledge. The work described in this thesis represents some of the first results in this area.

High intensity focused ultrasound (HIFU) is an emerging non-invasive thermal ablative modality that can be utilised for the treatment of solid organ tumours, including liver cancer. Acoustic cavitation is a phenomenon that can occur during HIFU and its presence can enhance heating rates. One major limitation of thermal ablative techniques in general, such as radiofrequency and microwave ablation, is the heat sink effect imparted by large vasculature. Thermal advection from blood flow in vessels &ge; 3 - 4 mm in diameter has been shown to significantly reduce heating rates and peak temperatures in the target tissue, potentially leading to treatment failure. With regards to HIFU therapy, a clearer understanding is required of the effects of blood flow on heating, cavitation and thermal tissue necrosis, which is the treatment endpoint in clinical thermal ablation. Therefore, the overall aim of this thesis project was to elucidate the effects of blood flow on HIFU-induced heating, cavitation and histological assessment of thermal ablation. A unique isolated, perfused porcine liver model was used in order to provide a relevant test bed, with physiological and anatomical characteristics similar to the in vivo human liver. The normothermic liver perfusion device used in all studies presented in this work can keep an organ alive in a functional state ex vivo for in excess of 72 hours. A further advantage of the liver perfusion device was that it allowed blood flow to be stopped completely and resumed rapidly, allowing studies to be conducted under zero flow conditions. A therapeutic HIFU system was used in order to deliver HIFU therapy to regions of hepatic parenchyma adjacent (&le; 3 mm) to large (&ge; 5 mm) blood vessels or away from vasculature (&ge; 1 cm) at either 1.06 MHz or at 3.18 MHz. Cavitation events during HIFU therapy were spatio-temporally monitored using a previously developed passive acoustic mapping (PAM) technique. The cavitation threshold at each frequency was determined through assessment of acoustic emissions acquired through PAM during HIFU exposure at a range of acoustic pressures. Real time thermal data during HIFU therapy were obtained using an implantable 400 &mu;m thermocouple, aligned with the HIFU focus, in order to assess the effect of large vessel blood flow on peak tissue temperatures. Thermal data were obtained at 1.06 MHz, in the presence of acoustic cavitation and at 3.18 MHz, in the absence of cavitation, both in the presence and complete absence of blood flow. Finally, histological assessment of cell viability and cell death was performed in order to determine whether any heat sink effect could be overcome, with the achievement of complete tissue necrosis in treatment regions directly adjacent to large vasculature. This work demonstrated for the first time that in perfused, functional liver tissue, the presence of large vasculature and physiological blood flow does not significantly affect ablative HIFU therapy, both in terms of peak focal tissue temperatures attained and histological evidence of complete tissue necrosis. Therefore, HIFU may be superior to other ablative modalities in treating tumours in tissue regions adjacent to major vascular structures, but further work needs to be performed to correlate the experimental findings with clinical outcomes.