The electrical energy consumption in thermomechanical pulping (TMP) is very high, in the range of 2 – 3 MWh/adt depending on process solution and on the product quality specifications for the paper product. Both pulpwood and energy prices have increased rapidly for some time. Due to this, the main focus of the research and development is on ways to reduce the electrical energy consumption in wood chip refining. As a step towards a more energy and cost ‐ effective refining process, Holmen Paper AB has invested in a new mechanical pulping process at its Braviken mill. In this case the primary refining stage consists of high consistency (HC) double disc refiners ‐ RGP68DD (machines with two counter rotating discs). Earlier studies on the refining conditions, such as intensity and temperature, have indicated that it should be possible to improve the energy efficiency in double disc refining while maintaining the functional pulp properties such as tensile index. The main goal of this project was to improve the energy efficiency in double disc chip refining with 150 kWh/adt to corresponding pulp properties as measured on pulp samples after refiner. In order to further improve the basic understanding of what happens to the wood fibre material when changing the process conditions, the morphological and ultrastructural changes of fibres were also studied. This part of the research work was performed in cooperation with the research program; Collaborative Research on the Ultrastructure of Wood Fibres (CRUW). This licentiate project is a part of a large development project where different techniques to improve the energy efficiency has been evaluated by means of mill scale trials at the Holmen Paper Braviken Mill. The high consistency double disc chip refining part of the project was financed by The Swedish Knowledge Foundation, Metso Paper and Holmen Paper, in cooperation with FSCN (Fiber Science & Communication Network) at Mid Sweden University. The trials were made on one of the TMP lines at the Holmen Paper Braviken mill with Norway spruce as raw material. The influence of increased specific      refining energy on pulp properties were studied at different refining temperatures, refining intensity, pulp consistency and production rate. Results from these trials were later validated by means of long term trials. Intensity models and simulations for intensity changes by new segment design were made by Juha‐ Pekka Huhtanen from Tampere University of Technology, Finland. The results show that the specific energy consumption to same tensile index can be improved by means of increasing the refining pressure/temperature. The energy efficiency was improved by 80     ‐150 kWh/adt depending on load and the inlet‐ and housing pressure. The largest relative specific energy efficiency improvement was reached at low specific energy consumption levels. Similar fibre surface ultrastructure characteristics are gained by pulps with high pressure/temperature and low specific energy consumption compared to low pressure/temperature and high specific energy consumption pulps. High pressure/temperature and high specific energy consumption resulted in significantly increase in the delamination/internal fibrillation of pulp fibres. The surface ultrastructure of these fibres exhibited exposed S2 layer with long ribbontype fibrillation compared to pulps produced with lower temperature and lower specific energy consumption. When the refiner was operated at high pressure, the tensile index was preserved over the whole plate life. The specific light scattering coefficient increased with increasing pressure/temperature. A reason for this could be increased intensity caused by decreased plate gap. Increased intensity by means of refiner segment design changes resulted in large specific light scattering coefficient increase at similar tensile index, lower shives content, lower average fibre length and lower CSF at same specific energy consumption. The fresh steam consumption was reduced by the increased refiner ressure/temperature. / Den höga elenergiförbrukningen vid produktion av mekanisk massa har ställtkrav på mer forskning för att elenergieffektivisera raffineringsprocessen. Som ettsteg mot en mer energi‐ och kostnadseffektiv raffineringsprocess, har HolmenPaper AB investerat i en ny tillverkning av termomekanisk (TMP) massa vidBravikens pappersbruk. Dubbeldiskraffinörerna i den nya massalinjens primäraraffineringssteget studerades i detta projekt. Det finns goda indikationer på att enminskning av energiförbrukningen är möjlig genom att studerar och optimeraraffineringparametrar såsom intensitet och temperatur. Projektets huvudmål varatt energieffektivisera det primära dubbeldiskraffineringssteget med 150 kWh/adttill motsvarande massaegenskaper, så som dragstyrka, mätt på massa efterraffinör. Tillfälle gavs också till att studera morfologiska förändringar på fibrer föratt ytterligare förstå hur massa och fibrerna påverkas av dubbeldiskraffinering ochförändringar i raffineringssystemet.Detta licentiatprojekt är en del av ett större projekt där olika tekniker för attförbättra energieffektiviteten har utvärderats i industriell skala på Holmen PaperBravikens pappersbruk. Licentiatprojektet är finansierat av KK‐stiftelsen, MetsoPaper och Holmen Paper, i samarbete med Mittuniversitetet.Fullskaleförsök gjordes på en av TMP linjerna vid Bravikens pappersbruk, därgran används som råvara. Studien utfördes på dubbeldiskraffinörerna i detprimära raffineringssteget. Malkurvor, med ökande specifik raffineringsenergi,gjordes vid olika raffineringstemperaturer, intensitet, massakoncentration ochproduktion. Resultat som erhållits från malkurvorna bekräftades med längrestudier på raffinörerna. Intensitetsmodeller och simuleringar utfördes av Juha‐Pekka Huhtanen från Tampere University of Technology.De erhållna resultaten visar på att energiförbrukningen till ett visst dragindexkan minskas genom att öka raffineringstrycket/temperaturen. Medraffineringstryck menas inlopp och hustryck i raffinören. Energibesparingen är iintervallet 80‐150 kWh/adt. Den största förbättringen kan uppnås vid lågaenergiinsatser. Massor producerade med högt tryck och temperatur och lägrespecifik energiförbrukning uppvisar liknande ultrastrukturella ytegenskaper sommassor producerade med lågt tryck och temperatur och hög specifik energi. Högttryck och temperaturer med hög specifik energiinsats gav en signifikant förbättringav delaminering/intern fibrillering av massafibrer. Dessa fibrer uppvisadebildningar av långa band‐liknande fibriller från fibrernas S2 skikt, i jämförelse medmassor tillverkade med lägre tryck och temperatur och lägre specifik energi.5Om raffineringen genomförs vid högt tryck/temperatur bevaras dragindexunder hela segmentlivslängden.Den specifika ljusspridningskoefficienten påverkades positivt av ökat tryck ochtemperatur. En orsak till detta kan vara högre intensitet som orsakas av minskadmalspalt.Ökad intensitet genom förändrad segmentdesign leder till stora ökningar i denspecifika ljusspridningskoefficienten. Samtidigt uppnås samma dragindex, lägrespethalt, lägre genomsnittlig fiberlängd och CSF vid samma specifikaenergiförbrukning.Förbrukningen av färskångan sänktes vid tillämning av högre tryck ochtemperatur i raffinören.

Every runner faces changes in speed and slope while exercising. While running faster or on a steepier surface represent different stimuli, both conditions lead to an increase in metabolic demand and therefore in heart rate (HR). The control of HR is given by both neural and non-neural components and can be accessed analyzing the heart rate variability (HRV). During exercise, HRV is known to be influenced by both sympathetic and parasympathetic branches of the autonomic nervous system, by breathing frequency, cadence, amongst other components. Hence, the present study sought to address how changes in speed and slope during running impact HR and HRV and whether the patterns observed for a restricted population were applicable to a broader group. We collected ECG records from volunteers divided into 2 groups: Experiment 1 (N = 12, with a broader range of ages and fitness level) and Experiment 2 (N = 9, composed of a more homogeneous population). Subjects ran on 9 (Experiment 1) or 16 (Experiment 2) combinations of speed and slope for a few minutes. Our data shows that the relationship between slope (%), relative speed (v) and relative HR is HR = 0.36 + 0.643 * v + 0.033 * s * v . HR behaved as predicted by a general equation of cost of locomotion in mammals and avians when it comes to the proportional impact of speed and slope, but not regarding the magnitude of such responses. This must reflect the loss of linearity between metabolic demand and HR at very high exercise intensities. Changes in HR could explain the behavior of most HRV estimators. However, one estimator (a1ApEn) could better be explained by changes in speed and slope. This indicates that HRV responds primarily to metabolic demand. The same general pattern of response of HRV to the different running conditions was observed in both groups, although, likely due to age-associated changes in cardiac control, how much a given HRV estimators changes differ between groups / Todo corredor se depara com mudanças de velocidade (v) e inclinação (i) durante o exercício. Correr mais rápido ou em uma superfície mais íngreme representam estímulos diferentes, porém ambos levam a um aumento na demanda metabólica e, portanto, na freqüência cardíaca (FC). O controle da FC é dado por componentes neurais e não neurais e pode ser acessado analisando-se a variabilidade da frequência cardíaca (VFC). Durante o exercício a VFC é influenciada pelos ramos simpático e parassimpático, freqüência ventilatória, cadência, dentre outros componentes. Assim, buscamos abordar como mudanças de velocidade e inclinação durante a corrida impactam a FC e a VFC e se os padrões observados para uma população restrita aplicam-se à um grupo mais amplo. Foram coletados registros de ECG de voluntários divididos em 2 grupos: Experimento 1 (N = 12, com faixa etária e nível de condicionamento físico mais amplos) e Experimento 2 (N = 9, composto por uma população mais homogênea). Os voluntários correram em 9 (Experimento 1) ou 16 (Experimento 2) combinações de velocidade e inclinação por alguns minutos. Nossos dados mostram que a relação entre inclinação (%), velocidade relativa (v) e FC relativa é FC = 0.36 + 0.643 * v + 0.033 * s * v . A FC se comportou como previsto por uma equação geral do custo de locomoção em mamíferos e aves quando se trata do impacto proporcional de velocidade e inclinação, mas não em relação à magnitude de tais respostas. Isso deve refletir a perda de linearidade entre a demanda metabólica e a FC em intensidades de exercício muito altas. Mudanças na FC explicam o comportamento da maioria dos estimadores de VFC. No entanto, um estimador (a1ApEn) foi melhor explicado por mudanças de velocidade e inclinação. Isso indica que a VFC responde principalmente à FC. O mesmo padrão de resposta da VFC às diferentes condições de corrida foi observado em ambos os grupos, embora, possivelmente devido à mudanças no controle cardíaco associadas à idade, o quanto um determinado estimadores se altera difere entre os grupos

Sabe-se que o aumento na temperatura do tecido tumoral pode aumentar a eficiência de técnicas convencionais de combate ao câncer (radioterapia e quimioterapia). Além disso, a variação de temperatura em tumores pode ser uma forma de tratamento alternativo à cirurgia, feito por meio do fornecimento de calor direcionado às células cancerosas e preservando o tecido sadio. Para maior eficácia e segurança no emprego de técnicas que utilizam fornecimento de calor ao tecido biológico, é necessário o monitoramento da temperatura tecidual para garantir que a morte celular por ablação térmica seja limitada ao tecido alvo, minimizando os danos aos tecidos adjacentes. A imagem fotoacústica é uma técnica baseada no efeito fotoacústico, o qual consiste na absorção de radiação eletromagnética pelo tecido e, devido à expansão termoelástica, na geração de ondas acústicas. A amplitude da onda de pressão gerada pelo efeito fotoacústico possui dependência com a temperatura do meio pelo parâmetro de Grueneisen, que depende das propriedades mecânicas do material. Portanto, mudanças na amplitude do sinal fotoacústico carregam informações a respeito da variação na temperatura do material. Neste trabalho, a dependência da amplitude do sinal fotoacústico com a temperatura foi estudada em um material simulador de tecido biológico (phantom) em condições similares a de tratamentos por hipertermia Nesse caso, imagens fotoacústicas foram adquiridas para cada grau de temperatura em uma faixa de 36 até 41 ºC durante o procedimento de aquecimento por banho térmico. Mudanças na amplitude e fase do sinal fotoacústico foram avaliadas através da aplicação de algoritmos de speckle tracking. Para estimar a variação na amplitude do sinal também foram utilizados e avaliados diferentes métodos de comparação. Os resultados são apresentados por imagens fotoacústicas termais produzidas pela aplicação de um fator de calibração aos mapas de variação relativa da amplitude do sinal em função da temperatura do meio. Finalmente, avaliamos um experimento de hipertemia por ultrassom focalizado de alta intensidade (High Intensity Therapeutic Ultrasound - HITU) em uma amostra de músculo suíno. Nesse caso foram geradas imagens termais fotoacústicas e imagens termais produzidas pela mudança de fase do sinal pulso-eco de ultrassom. Os resultados sugerem uma maneira não invasiva de calcular a distribuição da variação de temperatura do meio que pode ser aplicada para monitoramento durante tratamentos que utilizam o fornecimento de calor ao tecido biológico. / Several studies have shown that elevating the temperature of tumoral tissue improves standard cancer treatments success rate (radiotherapy and chemotherapy). This procedure can also be a therapy to cancer by delivering heat and killing cancer cells while healthy tissues are preserved. For improved efficiency and security in heat applications, it is important to monitor tissue temperature during treatments. Photoacoustic (PA) pressure wave amplitude has a temperature dependence given by the sample mechanical properties (Gruenesein parameter). These changes in photoacoustic signal amplitude carry information about temperature variation in tissue. Therefore, PA has been proposed as an imaging technique to monitor temperature during hyperthermia. In this study, PA images were acquired for temperatures ranging from 36ºC to 41ºC using a tissue-mimicking phantom immersed in a temperature controlled thermal bath. Relative amplitude variation was calculated using speckle tracking algorithms using four different methods to estimate these variations in PA signal amplitude. The results are presented as PA-based thermal images, generated using a calibration factor to the percentage variations in the amplitude maps. Finally, PA-based and ultrasound-based thermal images were acquired during heating by high intensity focused ultrasound (High Intensity Therapeutic Ultrasound - HITU) in a porcine muscle. The results suggest a non-invasive way to monitor temperature during hyperthermia procedures.

A síndrome metabólica (SM) é uma somatória de fatores de risco para desenvolvimento de doenças cardiovasculares (DCV), intimamente ligada à obesidade e, assim como a última, sua prevalência cresce mundialmente. Sua etiologia é complexa e suas causas são influenciadas por fatores ambientais e genéticos. Sabe-se que a elevação da capacidade cardiorrespiratória (VO2máx) seja um melhor atenuador do risco de mortalidade por DCV do que a própria obesidade. Atualmente a forma conhecida para aumento do VO2máx é o exercício físico aeróbio, porém vários indivíduos reportam falta de tempo para realização de uma rotina de exercícios físicos. Neste contexto, o presente trabalho teve como objetivo comparar dois protocolos de treinamento aeróbio de alta intensidade e outro contínuo de moderada intensidade quanto à influência na capacidade cardiorrespiratória, variáveis de síndrome metabólica (circunferência da cintura - CC, glicemia de jejum, HDL, triglicérides e pressão arterial) e composição corporal (massa e percentual de gordura) em indivíduos com sobrepeso/obesidade e; observar a influência de polimorfismos dos genes visfatina e receptor tipo 1 de angiotensina 2 (AGTR1) nos níveis de glicemia, HDL, triglicérides e pressão arterial. 40 indivíduos foram divididos aleatoriamente em três grupos de treinamento: contínuo moderado (CM), 4x1 e 4x4. O grupo CM realizou cinco sessões semanais de treino por 30 minutos; os grupos 4x1 e 4x4 realizaram 3 sessões semanais com duração de 19 e 40 minutos, respectivamente. A intervenção durou 16 semanas e as sessões foram monitoradas quanto à frequência cardíaca para controlar a intensidade do exercício. O grupo CM se exercitou a 70% da frequência cardíaca máxima, enquanto os grupos 4x1 e 4x4 realizaram estímulos a 90% da frequência cardíaca máxima. Os resultados encontrados apontaram uma melhora na capacidade cardiorrespiratória em todos os grupos, sem diferença entre eles. Diminuição da massa corpórea, IMC, percentual de gordura somente no grupo 4x4. Diminuição de CC nos grupos 4x4 e CM. Os dados da análise genética não apontaram nenhuma relação entre os polimorfismos avaliados e as variáveis de interesse. Por fim, concluiu-se que o treinamento de alta intensidade com duração de 19 minutos promove resultados semelhantes ao treinamento de mesma intensidade e duração de 40 minutos e ao treinamento de intensidade moderada na capacidade cardiorrespiratória em indivíduos com sobrepeso/obesidade, sendo uma alternativa viável para treinamento físico com pouco volume. / Metabolic syndrome (MS) is a sum of risk factors for developing cardiovascular disease (CVD), closely linked to obesity and, like the latter, its prevalence is growing worldwide. Its etiology is complex and its causes are influenced by environmental and genetic factors. It is known that the increase in cardiorespiratory fitness (VO2max) is a better attenuator of CVD mortality risk rather than obesity itself. Currently, the best known way to increase VO2max is aerobic exercise, but many people report lack of time to perform a exercise routine exercise. In this context, this study aimed to compare two high intensity aerobic exercise protocols and a continuous moderate exercise regarding their effects on cardiorespiratory fitness, metabolic syndrome variables (waist circumference - WC, fasting plasma glucose, HDL, triglycerides, and blood pressure) and body composition (body mass and fat percentage) in overweight/obese individuals and; observe the influence of genetic polymorphisms of visfatin and angiotensin 2 receptor type 1(AGTR1) in blood glucose levels, HDL, triglycerides and blood pressure. 40 subjects were randomly divided into three training groups: continuous moderate intensity (CM), 4x1 and 4x4. The CM group held five weekly training sessions for 30 minutes; the 4x1 and 4x4 groups performed three weekly sessions lasting 19 and 40 minutes, respectively. The intervention lasted 16 weeks and the sessions were monitored for heart rate to control the exercise intensity. The CM group exercised at 70% of maximum heart rate, while the 4x1 and 4x4 groups performed stimuli to 90% of maximum heart rate. The findings showed an improvement in cardiorespiratory fitness in all groups, with no difference between them. A decreased body mass, BMI, body fat percentage only in the group 4x4. WC decrease in 4x4 and CM groups. Data from genetic analysis did not show any relationship between the evaluated polymorphisms and the variables of interest. Finally, it was concluded that the high intensity training lasting 19 minutes promotes similar results to the training of the same intensity and duration of 40 minutes and moderate intensity training on cardiorespiratory fitness in overweight/obese individuals, being a viable alternative for exercise training with low volume.

O objetivo deste estudo foi avaliar, in vitro, a resistência de união de retentores intrarradiculares previamente irradiada com laser de diodo em alta intensidade (&lambda;= 830 nm), tanto em regime contínuo como pulsado. Foram utilizados retentores intrarradiculares metálicos ou de fibra de vidro, cimentados com fosfato de zinco ou cimento resinoso auto-condicionante. Assim, as variáveis analisadas foram o regime de irradiação, o tipo de retentor intrarradicular e o tipo de agente cimentante na resistência de união. Estas variáveis foram analisadas, in vitro, nos 3 terços radiculares (cervical, médio e apical) de 90 dentes humanos endodonticamente tratados, preparados para receber retentor intrarradicular e irradiados com laser de diodo em alta intensidade (830 nm). Após a irradiação os retentores foram cimentados com cimento de fosfato de zinco ou com cimento resinoso autocondicionante. As raízes foram seccionadas por meio de cortes transversais dos terços cervical, médio e apical, obtendo-se, assim, seis amostras de cada raiz. Cada uma das amostras foi submetida ao ensaio de resistência de união de maneira cega. Conclui-se que a resistência mecânica à compressão de retentores intrarradiculares em dentina previamente irradiada com laser de diodo de alta intensidade (&lambda;= 830 nm) apresentou maiores valores na dentina intrarradicular tanto no regime contínuo como pulsado, sendo ligeiramente superior no regime pulsado. Foi possível verificar que, nos terços médio e cervical, a irradiação com laser de diodo pulsado (Pm = 1 W, I = 994 W/cm2) resultou em maiores valores de resistência de união, com ambos os cimentos e ambos os tipos de núcleo. Houve diferença estatisticamente significante nos valores de união nos diferentes terços dos grupos tratados, sendo superior para o terço cervical (p < 0,05). Assim, a técnica de irradiação do conduto com laser de diodo mostrou-se eficaz no aumento da resistência de união de retentores intrarradiculares. / The aim of this study was to evaluate, in vitro, the bond strength of intracanal post cemented on irradiated dentin by a high intensity diode laser (&lambda; = 830 nm), both continuous and pulsed regime. Metal or fiber glass posts were used and cemented with zinc phosphate cement or self-etching resin-based cement. Thus, the variables analyzed were the regime of irradiation, the type of post and type of luting agent on bond strength. These variables were analyzed in vitro the 3 root thirds (cervical, middle and apical) of 90 endodontically treated human teeth prepared to receive posts and irradiated with diode laser at high intensity (830 nm). After irradiation, posts were cemented with zinc phosphate or self-etching resin cement. The roots were transversely in the cervical, middle and apical thirds, resulting in six samples each root. Each sample was subjected to the test of bond strength blindly. We concluded that the mechanical strength of intracanal posts cemented on dentin irradiated by high intensity diode laser (&lambda; = 830 nm) showed higher adhesion values in dentin, both for continuous and pulsed regime, being slightly higher in the pulsed regime. It was possible to verify that in the cervical and middle thirds, irradiation with pulsed diode laser (Pm = 1 W, I = 994 W/cm2) resulted in higher bond strength using both cements and both types posts. There was a significant difference among the different thirds of the treated groups, being higher for the cervical third (p < 0,05). So, irradiation with diode laser was effective to increase the resistence of union of intrarradicular posts.

O objetivo deste estudo foi avaliar, in vitro, a resistência de união de retentores intrarradiculares previamente irradiada com laser de diodo em alta intensidade (&lambda;= 830 nm), tanto em regime contínuo como pulsado. Foram utilizados retentores intrarradiculares metálicos ou de fibra de vidro, cimentados com fosfato de zinco ou cimento resinoso auto-condicionante. Assim, as variáveis analisadas foram o regime de irradiação, o tipo de retentor intrarradicular e o tipo de agente cimentante na resistência de união. Estas variáveis foram analisadas, in vitro, nos 3 terços radiculares (cervical, médio e apical) de 90 dentes humanos endodonticamente tratados, preparados para receber retentor intrarradicular e irradiados com laser de diodo em alta intensidade (830 nm). Após a irradiação os retentores foram cimentados com cimento de fosfato de zinco ou com cimento resinoso autocondicionante. As raízes foram seccionadas por meio de cortes transversais dos terços cervical, médio e apical, obtendo-se, assim, seis amostras de cada raiz. Cada uma das amostras foi submetida ao ensaio de resistência de união de maneira cega. Conclui-se que a resistência mecânica à compressão de retentores intrarradiculares em dentina previamente irradiada com laser de diodo de alta intensidade (&lambda;= 830 nm) apresentou maiores valores na dentina intrarradicular tanto no regime contínuo como pulsado, sendo ligeiramente superior no regime pulsado. Foi possível verificar que, nos terços médio e cervical, a irradiação com laser de diodo pulsado (Pm = 1 W, I = 994 W/cm2) resultou em maiores valores de resistência de união, com ambos os cimentos e ambos os tipos de núcleo. Houve diferença estatisticamente significante nos valores de união nos diferentes terços dos grupos tratados, sendo superior para o terço cervical (p < 0,05). Assim, a técnica de irradiação do conduto com laser de diodo mostrou-se eficaz no aumento da resistência de união de retentores intrarradiculares. / The aim of this study was to evaluate, in vitro, the bond strength of intracanal post cemented on irradiated dentin by a high intensity diode laser (&lambda; = 830 nm), both continuous and pulsed regime. Metal or fiber glass posts were used and cemented with zinc phosphate cement or self-etching resin-based cement. Thus, the variables analyzed were the regime of irradiation, the type of post and type of luting agent on bond strength. These variables were analyzed in vitro the 3 root thirds (cervical, middle and apical) of 90 endodontically treated human teeth prepared to receive posts and irradiated with diode laser at high intensity (830 nm). After irradiation, posts were cemented with zinc phosphate or self-etching resin cement. The roots were transversely in the cervical, middle and apical thirds, resulting in six samples each root. Each sample was subjected to the test of bond strength blindly. We concluded that the mechanical strength of intracanal posts cemented on dentin irradiated by high intensity diode laser (&lambda; = 830 nm) showed higher adhesion values in dentin, both for continuous and pulsed regime, being slightly higher in the pulsed regime. It was possible to verify that in the cervical and middle thirds, irradiation with pulsed diode laser (Pm = 1 W, I = 994 W/cm2) resulted in higher bond strength using both cements and both types posts. There was a significant difference among the different thirds of the treated groups, being higher for the cervical third (p < 0,05). So, irradiation with diode laser was effective to increase the resistence of union of intrarradicular posts.

O objetivo do presente estudo foi verificar os efeitos do treinamento intervalado de alta intensidade (TIAI), específico e não específico, sobre respostas fisiológicas e desempenho em testes aeróbios e anaeróbios, bem como sobre ações técnicas e táticas durante a luta de judô. 35 atletas de judô realizaram uma série de testes antes e após quatro semanas de treinamento, sendo aleatoriamente divididos em quatro grupos: TIAI para membros inferiores, TIAI para membros superiores, TIAI específico [por meio de entrada de golpes (uchi-komi)] e grupo controle. Os grupos experimentais treinaram o exercício intervalado de alta intensidade (EIAI) adicionalmente ao treino de judô e o grupo controle realizou apenas judô. Foi utilizado o mesmo tipo de estímulo em regiões corporais distintas: realização de duas sessões semanais de EIAI constituídas por dois blocos de 10 estímulos de 20s por 10s de intervalo entre os estímulos e 5 min entre os blocos, i.e., grupo de membros superiores e inferiores utilizaram cicloergômetros específicos para cada região corporal, enquanto o grupo específico desempenhou uchi-komi em intensidade all-out com atleta de massa corporal similar. Os grupos e momentos foram comparados via análise de variância (ANOVA) a dois fatores (grupo e momento do treinamento) ou a três fatores (grupo, momento do treinamento e momento da medida), seguida pelo teste de Bonferroni. Quando encontrada diferença entre os grupos durante as semanas de treinamento, foi efetuada uma ANOVA a um fator com medidas repetidas, bem como o teste-t pareado para os valores pré e pós-treinamento. Os principais resultados apontam que: para o grupo de membros inferiores houve aumento da potência equivalente ao onset blood lactate accumulation (OBLA) no teste progressivo para membros superiores, aumento da potência média no teste de Wingate adaptado para membros inferiores, redução da frequência cardíaca após o Special Judo Fitness Test (SJFT), redução do número de sequências em pé durante a simulação de luta e aumento da razão testosterona/cortisol (T/C) pós-simulação de luta no momento pós-treinamento; para o grupo de membros superiores, houve elevação da potência aeróbia máxima no teste progressivo máximo para membros superiores, aumento do número total de projeções no SJFT, redução das concentrações de CK e elevação da razão T/C pós-simulação de luta no pós-treinamento, bem como elevação das concentrações de LDH nas mensurações conduzidas em repouso; para o grupo uchi-komi, houve aumento da potência pico no teste de Wingate para membros superiores e inferiores, redução do índice no SJFT e aumento da razão T/C pós-simulação de luta no momento pós-treinamento. Não foram detectadas alterações no desempenho para o grupo controle pós-treinamento. Além disso, não foram detectadas quaisquer alterações para as respostas psicométricas, hormonais, assim como para o sistema nervoso autônomo após as quatro semanas de intervenção. Os resultados indicam que a adição do TIAI à rotina de treinamento usual de judô eleva a potência aeróbia máxima para membros superiores e desempenho intermitente de alta intensidade para membros superiores e inferiores em testes genéricos. Adicionalmente, o TIAI melhora aspectos relevantes para o desempenho em tarefas específicas do judô. Por fim, o TIAI de baixo volume não promoveu alterações nas respostas do sistema nervoso autônomo, questionários psicométricos e respostas hormonais ao longo das quatro semanas de treinamento / The aim of the present study was to verify the effects, specific and non-specific, of high intensity interval training (HIIT) on physiological and performance responses to aerobic and anaerobic tests, as well as on technical and tactical actions during judo combat. In order to achieve this purpose, 35 judo athletes were randomly selected into four groups: HIIT for lower-body, upper-body, specific group (by means of technique-entrance, uchi-komi) and a control group. These groups completed a series of tests, before and after a 4-week training period. The experimental groups did high intensity interval exercise (HIIE) in addition to judo training while the control group did judo training only. The same type of stimulus was used on distinct body regions: two weekly sessions of HIIE consisting of two blocks of 10 x 20s stimuli with a 10s interval between stimuli and a 5-min interval between blocks, i.e., the lower and upper-body group used cycle-ergometer for each body region, while the specific group carried out uchi-komi at all-out intensity with another athlete of similar body mass and stature. The groups and moments were compared via variance analysis (ANOVA) to two factors (group and training) or to three factors (group, training and time of measurement), followed by the Bonferroni test. When a difference was detected between groups during the training weeks, a one-way (ANOVA) was carried out with repeated measures, as well as the paired t-test, for pre and post-training values. The main results indicate that: The lower-body group showed increase in the equivalent power to onset blood lactate accumulation (OBLA), in aerobic fitness test for upper- limbs, increase in the mean power in the Wingate test (4 sets of 30s interspersed with 3-min recovery period) for lower limbs, heart rate reduction after the Special Judo Fitness Test (SJFT), reducing the number of standing sequences during the match simulation and increasing the testosterone/cortisol ratio (T/C) after the match simulation in the post-training period; For the upper-body group, showed an increase of the maximum aerobic power in aerobic fitness test for upper limbs, increase in the total number of projections in SJFT, reduced CK concentrations (post-training period), increase in T/C ratio post-match in the post-training period and increase in LDH concentrations in measurements conducted at rest. Uchi-komi group, showed an increased in the peak power in the Wingate test for upper and lower limbs, reduction of the SJFT index and increasing the T/C ratio after the match-simulations in the post-training period. As expected, were not found any performance changes after 4-weeks of intervention for the control group Furthermore, were not detected any changes to the psychometric, hormonal responses, as well as the autonomic nervous system after four weeks of intervention for all experimental groups. Therefore, these findings suggest that addition of the HIIT to usual judo training increases the maximum aerobic power for upper limbs and high-intensity intermittent performance for upper and lower limbs, in generic tests. Moreover, HIIT improves relevant aspects to performance in specific judo tasks. Finally, low volume HIIE did not bring about any alterations to the autonomous nervous system responses, psychometric responses or hormonal responses throughout the four weeks of training

Despite clear recommendations on the minimal amount of physical activity for achieving health benefits and reducing risk of chronic disease, the majority of people in the Western world remain sedentary. As a 'lack of time' has been identified as one of the main barriers to becoming and remaining physically active, in the past decade research has focused on high-intensity interval training (HIT) as a time-efficient alternative to aerobic exercise. Although initial studies convincingly demonstrated equal or better health benefits with various HIT protocols compared to much larger volumes of aerobic exercise, these HIT protocols tend to be very strenuous and as such are unlikely to be adhered to by sedentary populations. Furthermore, most HIT protocols are not as time-efficient as sometimes claimed, with the total time per exercise session generally exceeding 20-30 minutes. This thesis aimed to characterise the effects of a novel reduced-exertion HIT (ReHIT) protocol, requiring a maximum of 2 x 20 s all-out sprint efforts in a 10 min training session, upon insulin sensitivity, aerobic capacity, glycogen utilisation and associated acute metabolic responses. The ReHIT exercise bouts were well tolerated by participants, but were associated with a substantial disturbance of physiological homeostasis including muscle glycogen degradation, lactate accumulation, excursions in plasma volume, post-exercise oxygen consumption, respiratory exchange ratio and heart rate, as well as a skeletal muscle signalling response through AMPK, and increases in skeletal muscle GLUT4 and PGC1α mRNA expression (Chapter 4 and 5). The combined training studies (n=49) provide some support for improvements in key disease biomarkers following ReHIT, with improvements in insulin sensitivity observed in men, and increased aerobic capacity observed in men and women (Chapter 7). These observations highlight a potential regulatory role for glycogen in exercise-induced adaptation. However, the mean improvements in insulin sensitivity in men were not consistent between the two training studies (Chapter 2 and 6), and there was a high level of variability observed between individuals (Chapter 6 and 7). Therefore, the impact of ReHIT on insulin sensitivity needs to be further explored in the context of a randomised controlled trial, and the mechanisms underpinning the large variability in adaptive response need to be characterised.

The blood-brain barrier (BBB) is physiologically essential for brain homeostasis. While it protects the brain from noxious agents, it prevents almost all currently available drugs from crossing to the parenchyma. This greatly hinders drug delivery for the treatment of neurological diseases and disorders such as Parkinson’s, Alzheimer’s and Huntington’s, as well as the development of drugs for the treatment of such diseases. Current drug delivery techniques to the brain are either invasive and target specific, or non-invasive with low special specificity. Neither group of techniques are optimal for long term treatment of patients with neurological diseases or disorders. Focused ultrasound coupled with intravenous administration of microbubbles (FUS) has been proven as an effective technique to selectively and noninvasively open the BBB in multiple in vivo models including non-human primates (NHP). Although this technique has promising potential for clinical outpatient procedures, as well as a powerful tool in the lab, the safety and potential neurological effects of this technique need to be further investigated. This thesis focuses on validating the safety and efficacy of using the FUS technique to open the BBB in NHP as well as the ability of the technique to facility drug delivery. First, a longitudinal study of repeatedly applying the FUS technique targeting the basal ganglia region in four NHP was conducted to determine any potential long-term adverse side effects over a duration of 4-20 months. The safety of the technique was evaluated using both MRI as well as behavioral testing. Results demonstrated that repeated application of the FUS technique to the basal ganglia in NHP did not generate permanent side effects, nor did it induce a permanent opening of the BBB in the targeted region. The second study investigated the potential of the FUS technique as a method to deliver drugs, such as a low dose of haloperidol, to the basal ganglia in NHP and mice to elicit pharmacodynamical effects on responses to behavioral tasks. After opening the BBB in the basal ganglia of mice and NHP, a low dose of haloperidol was successfully delivered generating significant changes in their baseline motor responses to behavioral tasks. Domperidone was also successfully delivered to the caudate of NHP after opening the BBB and induced transient hemilateral neglect. In the final section of this thesis, the safety and efficacy of the FUS technique was evaluated in fully alert NHP. The FUS technique was successful in generating BBB opening volumes larger on average to that of the BBB opening volumes in anesthetized experiments. Safety results through MRI verification as well as behavioral testing during application of the technique demonstrated that the FUS technique did not generate adverse neurological effects. Conversely, the FUS technique was found to induce slight positive effects on the response of the NHP to the behavioral task. Collectively, the work presented in this thesis demonstrates the safety and effectiveness of the FUS technique to open the BBB and deliver neuroactive drugs in the NHP.

Damage to articular cartilage, whether through degeneration (i.e. osteoarthritis) or acute injury, is particularly debilitating due to the tissue's limited regenerative capacity. These impairments are common: nearly 27 million Americans suffer from osteoarthritis and 36% of athletes suffer from traumatic cartilage defects. Allografts are the preferred treatment for large cartilage defects, but demand for these tissues outweighs their supply. To generate additional replacement tissues, tissue engineering strategies have been studied as a cell-based alternative therapy. Our laboratory has had great success repeatedly achieving native or near-native mechanical and biochemical properties in grafts engineered from chondrocyte-seeded agarose hydrogels. The most common iteration of this technique yields a disk of ~4 mm diameter and ~2.3 mm thickness. However, much work is still needed to increase the potential for clinical translation of this product. Our laboratory operates under the premise that in vivo success is predicated on replicating native graft properties in vitro. Compared to these engineered grafts, native grafts are larger in size. They consist of cartilage, which has properties varying in a depth-specific manner, anchored to a porous subchondral bone base. They are able to be stored between harvest and transplantation. This dissertation presents strategies to address a subset of the remaining challenges of reproducing these aspects in engineered grafts. First, graft macrostructure was addressed by incorporating a porous base to generate biomimetic osteochondral grafts. Previous studies have shown advantages to using porous metals as the bony base. Likewise, we confirmed that osteochondral constructs can be cultured to robust tissue properties using porous titanium bases. The titanium manufacturing method, selective laser melting, offers precise control, allowing for tailoring of base shape and pore geometry for optimal cartilage growth and osteointegration. In addition to viability studies, we investigated the influence of the porous base on the measured mechanical properties of the construct's gel region. Through measurements and correlation analysis, we linked a decrease in measured mechanical properties to pore area. We promote characterization of such parameters as an important consideration for the generation of functional grafts using any porous base. Next, we investigated a high intensity focused ultrasound (HIFU) denaturation of gel-incorporated albumin as a strategy for inducing local tissue property changes in constructs during in vitro growth. HIFU is a low cost, non-contact, non-invasive ultrasound modality that is used clinically and in the laboratory for such applications as ablation of uterine fibroids and soft tissue tumors. Denaturing such proteins has been shown to increase local stiffness. We displayed the ability incorporate albumin into tissue engineering relevant hydrogels, alter transport properties, and visualize treatment with its denaturation. HIFU treatment is aided by the porous metal base, allowing for augmented heating. Though heating cartilage is used in the clinic, it is associated with cell death. We investigated this effect, finding that the associated loss of viability remains localized to the treatment zone over time. This promotes the option of balancing desired changes in tissue properties against the concomitant cell viability loss. In order to match clinically utilized allografts, engineered constructs must be scaled up in size. This process is limited by diffusional transport of nutrients and other chemical factors, leading to preferential extracellular matrix deposition in the construct periphery. Many methods are being investigated for overcoming this limitation in fixed-size constructs. In this chapter, we investigated a novel strategy in which small constructs are cultured for future assembly. This modular assembly offers coverage of variable sized defects with more consistent growth with more uniform distribution of biochemical constituents than large constructs cultured on their own. Physiologic failure testing showed that integration of these tissues may be strengthened by increased subunit strength or assembled culture. It is expected that bioadhesive caulking and/or the incorporation of osteochondral bases would further increase integration of the assembled large graft. Finally, we sought to provide a preservation/storage protocol for engineered cartilage constructs. Such a technique is critical for clinical translation, providing the engineered graft with a “shelf-life.” We adopted and evaluated the Missouri Osteochondral Allograft Preservation System (MOPS), which had been shown to maintain cell viability in native grafts for at least 63 days at room temperature without serum or growth factors. Within the current clinical of 28 days, MOPS maintained chondrocyte viability and 75% of the pre-preservation Young's modulus without significant decline in biochemical content, however it did not extend the clinical window as it had with native grafts. Refrigeration with MOPS did not show any benefit at day 28, but proved better with longer preservation times. These results are the first evaluating engineered cartilage storage. Further optimization is necessary to extend storage tissue property maintenance in storage. Overall, this dissertation presents four strategies for increasing the translation potential of engineered articular cartilage grafts by better matching the clinically utilized native allograft system. Combining these techniques, one could ideally engineer small, interlocking ostechondral constructs with HIFU modified interface properties, which could be stored from maturity to implantation. Future optimization is required to better understand and utilize these methods to engineer fully functional, clinically relevant grafts.