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Endurance can be defined as the ability to maintain or to repeat a given force or power output. The sport performance-endurance relationship is a multi-factorial concept. However, evidence indicates that maximum strength is a major component. Conceptually, endurance is a continuum. The literature indicates that (a) maximum strength is moderately to strongly related to endurance capabilities and associated factors, a relationship that is likely stronger for high intensity exercise endurance (HIEE) activities than for low intensity exercise endurance (LIEE); (b) strength training can increase both HIEE and LIEE, the effect being greater for HIEE; (c) the volume of strength training plays a role in endurance adaptation; and (d) mechanical specificity and training program variables also play a role in the degree of adaptation..

<p>This thesis investigated the acute and chronic responses of human skeletal muscle to high-intensity exercise, with a particular focus on markers of mitochondrial content, and the potential for nutrition to manipulate the adaptive response in recreationally active individuals. The acute response was primarily assessed via measurement of signalling proteins and mRNA species linked to exercise-induced mitochondrial biogenesis. The chronic response was determined via changes in the protein content or maximal activities of mitochondrial enzymes after training. Study 1 examined whether the manner in which a given amount of high-intensity cycling work was performed (i.e., in an intermittent or continuous fashion) altered the acute metabolic response to exercise, and whether the acute response was indicative of longer-term adaptations. Despite the similar acute activation of signalling proteins after the intermittent and continuous matched-work exercise protocols, 6 wk of training with the continuous protocol did not increase mitochondrial content, contrary to what we have previously shown after 6 wk training with the intermittent protocol. This suggests that the intermittent application of a low-volume, high-intensity stimulus is important to elicit training-induced increases in mitochondrial content. Furthermore, Study 1 showed that acute changes in specific signalling proteins did not necessarily predict chronic adaptations. Studies 2 and 3 examined whether specific nutritional interventions, previously shown to modulate acute exercise capacity or metabolic response, altered the mitochondrial adaptive response to several weeks of HIT. Neither manipulating carbohydrate availability between twice daily training sessions, or chronic ingestion of β-alanine, augmented skeletal muscle adaptations in response to 2-6 wk of HIT. It is possible that small influences of nutrition were overwhelmed by the potency of HIT, which stimulated marked increases in mitochondrial content in this population. Overall this thesis advances our basic understanding of the skeletal muscle adaptive response to HIT and the influence of nutrition.</p> / Doctor of Philosophy (PhD)

<p>This thesis examined the effect of high-intensity "sprint" interval training (SIT) on aerobic-based exercise performance and metabolic adaptations in human skeletal muscle. It has long been recognized that several weeks of interval-based training increased skeletal muscle oxidative capacity; however, little was known regarding the minimum "dose" of SIT necessary to elicit this adaptive response or the time-course and magnitude of adaptation in other markers of skeletal muscle metabolic control. Our general hypothesis was that low-volume SIT would induce rapid improvements in a wide array of metabolic variables that were comparable to traditional high-volume endurance training (ET). Healthy young men and women were recruited to perform four to six 30- second "all out" Wingate Tests, three times per week with one to two days of recovery, for up to six weeks. The weekly dose of SIT corresponded to ~10 minutes of maximal cycling exercise (-225-300 kJ) over a total training time commitment of 60-90 minutes, including recovery. The SIT response was compared against control subjects who performed no training or an ET group who performed up to one hour per day of moderate-intensity cycling exercise, five days per week for six weeks (-2250 kJ per week). Our major findings were that one to two weeks of SIT increased performance during aerobic-based exercise (time-to-fatigue tests and time-trials of varying duration) and the maximal activity or total protein content of mitochondrial enzymes and transport proteins associated with carbohydrate metabolism (e.g., citrate synthase, cytochrome oxidase, glucose transporter 4). Six weeks of SIT or ET induced similar increases in markers of skeletal muscle carbohydrate (pyruvate dehydrogenase E1a protein content) and lipid oxidation (3-hydroxyacyl CoA dehydrogenase maximal activity) and peroxisome-proliferator-activated receptorgamma coactivator-1a protein content, and similar reductions in phosphocreatine and glycogen utilization during matched-work exercise. These data suggest that SIT is a time-efficient strategy to increase skeletal muscle oxidative capacity and to induce specific metabolic adaptations during exercise that are comparable to ET.</p> / Doctor of Philosophy (PhD)

<p>Research in this thesis has focused on development and application of novel methodologies that enhance sample throughput and data fidelity when performing untargeted metabolome profiling by multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). Metabolomics is a valuable tool in functional genomics research to investigate underlying molecular mechanisms associated with human health since metabolites are “real-world” end-products of gene expression. CE-MS is well-suited for metabolomics because it is a high efficiency microseparation technique that can be used to resolve complex mixtures of polar metabolites in human biofluids without complicated sample workup. In this thesis, a novel CE-MS assay for estrogens and their intact ionic conjugates has been described (<em>Chapter II</em>) to expand metabolome coverage that enables resolution of positional isomers with high selectivity. This is critical for better understanding of underlying perturbations in estrogen metabolism since the biological activity of estrogens are dependent on specific primary and secondary metabolic transformations. MSI-CE-MS has been introduced as a high-throughput approach for large-scale metabolomic studies based on serial injection of multiple segments of sample within a single fused-silica capillary (<em>Chapter III</em>). It reduces analysis times while increasing data quality and confidence in peak assignment together with better quality assurance. An accelerated workflow for metabolomics has also been developed when using MSI-CE-MS, where a dilution trend filter is used as a primary screen to authenticate reproducible sample-derived metabolites from a pooled sample while eliminating spurious artifact and background signals. In this way, complicated time alignment and peak picking algorithms are avoided when processing data in metabolomics to reduce false discoveries. This strategy was subsequently used in two metabolomics applications (<em>Chapters IV</em> and <em>V</em>) to identify plasma markers associated with strenuous exercise and adaptive training responses following a six-week high intensity interval training. The impact of exercise intervention to improve the glucose tolerance of a cohort of overweight/obese yet non-diabetic women was investigated on an individual level when using a cross-over design. Personalized interventions are critical in designing more effective therapies to prevent metabolic diseases due to inter-subject variations in treatment responses, including potential adverse effects. MSI-CE-MS offers a revolutionary approach for biomarker discovery in metabolomics with high sample throughput and high data fidelity, which is critical for validation of safe yet effective lifestyle interventions that promote human health and reduce risk for chronic diseases.</p> / Doctor of Philosophy (PhD)

<p>What a ride it has been. The ups and downs of the McMaster graduate program has been a sweet one. It has been a pleasure working with the Exercise Metabolism Research Group for the past 2 years, and I will miss being around the work that goes on in the trenches around the lab. I have leaned on many people for all types of guidance through this journey, and would like to thank everyone for their unprecedented support. I have grown as a person and student and will use everything I have learned at this fine establishment I’m sure at one point or another along the great path of life. I must thank my amazing parents, family, friends and of coarse Ashley for putting up with my work ethic throughout my studies; the long days that I would go missing. Without their support none of this would have been possible. I have to specially mention Melanie Wolfe for recommending myself, and ultimately Stu Phillips for presenting this opportunity that is coming to a close. I have had great senior support from Cam Mitchell, Tyler Churchward-Venne, Todd Prior and Michaela Devries in putting this document together, and would not be submitting this without their selfless assistance. It’s been a journey getting to this point, but I wouldn’t change it for the world, to the next chapter in life, cheers and God Bless.</p> / <p>Higher dietary protein intake, greater than the Recommended Dietary Allowance (RDA; 0.8 g protein/kg/d), coupled with resistive exercise has been shown to aid in preservation of muscle mass during hypocaloric diet-induced weight loss. We examined the impact of dietary protein supplementation at two levels (1.2 and 2.4 g/kg/d) on body composition during a 4wk hypocaloric dietary intervention that included 6d/wk of high intensity resistance exercise and interval training. In a single blind study, forty young men consumed 33±1.1 kcal/LBM (~40% reduction versus estimated energy requirements), and were randomly assigned to a group that consumed either 1.2g/kg/d protein or 2.4g/kg/d. Body composition was determined using DXA, Bod Pod, and Bio-impedance pre- and post-intervention to derive a 4-compartment model for body composition. Both groups retained lean mass (LM), but retention was greater in the higher protein group (p</p> / Master of Science (MSc)

Focused ultrasound (FUS) is an emerging technology, and it plays an essential role in clinical and contactless acoustic energy transfer applications. These applications have critical criteria for the acoustic pressure level, the creation of complex pressure patterns, spatial management of the complicated acoustic field, and the degree of nonlinear waveform distortion at the focal areas, which have not been met to date. This dissertation focuses on introducing experimentally validated novel numerical approaches, optimization algorithms, and experimental techniques to fill existing knowledge gaps and enhance the functionality of holographic acoustic lenses (HALs) with an emphasis on applications related to biomedical-focused ultrasound and ultrasonic energy transfer. This dissertation also aims to investigate the dynamics of nonlinear acoustic beam shaping in engineered HALs. First, We will introduce 3D-printed metallic acoustic holographic mirrors for precise spatial manipulation of reflected ultrasonic waves. Optimization algorithms and experimental validations are presented for applications like contactless acoustic energy transfer. Furthermore, a portion of the present work focuses on designing holographic lenses in strongly heterogeneous media for ultrasound focusing and skull aberration compensation in transcranial-focused ultrasound. To this end, we collaborated with the Biomedical Engineering and Mechanics Department as well as Fralin Biomedical Research Institute to implement acoustic lenses in transcranial neuromodulation, targeting to improve the quality of life for patients with brain disease by minimizing the treatment time and optimizing the ultrasonic energy into the region of interest. We will also delve into the nonlinear regime for High-Intensity Focused Ultrasound (HIFU) applications, this study is structured under three objectives: (1) establishing nonlinear acoustic-elastodynamics models to represent the dynamics of holographic lenses under low- to high-intensity acoustic fields; (2) validating and leveraging the resulting models for high-fidelity lens designs used in generating specified nonlinear ultrasonic fields of complex spatial distribution; (3) exploiting new physical phenomena in acoustic holography. The performed research in this dissertation yields experimentally proven mathematical frameworks for extending the functionality of holographic lenses, especially in transcranial-focused ultrasound and nonlinear wavefront shaping, advancing knowledge in the burgeoning field of the inverse issue of nonlinear acoustics, which has remained underdeveloped for many years. / Doctor of Philosophy / Ultrasonic waves are sound waves that have frequencies higher than the upper audible limit of human hearing. The versatility and non-invasive nature of ultrasonic waves make them a valuable tool in numerous scientific, medical, and industrial applications. In healthcare, ultrasonic waves are employed in diagnostic imaging techniques, such as ultrasound scans, to create images of internal body structures. Ultrasonic waves are also used for non-destructive testing (NDT) of materials, detecting flaws or cracks within structures without causing any damage. Furthermore, this technology finds applications in the field of material science for the manipulation of particles and in biomedical research for drug delivery systems. Focused ultrasound sound is an emerging non-invasive therapeutic modality that uses focused ultrasound waves to target tissue within the body without damaging the surrounding tissue. This technology allows for precise delivery of ultrasound energy to a specific region, where it can induce various desired therapeutic effects depending on the targeting location and parameters. Therapeutic focused ultrasound has the advantage of being non-invasive, reducing the risks and recovery time associated with traditional surgery. It can be precisely controlled and monitored in real-time with imaging techniques such as ultrasound or MRI, ensuring the targeted treatment of pathological tissues while sparing healthy ones. Applications of therapeutic are broad and include tumor ablation, facilitation of drug delivery across the blood-brain barrier, relief of chronic pain, and treatment of essential tremor and other neurological disorders. The domain of therapeutic focused ultrasound is continually advancing, driven by research that seeks to extend its applications. Recent developments in acoustic engineering and 3D printing have led to the creation of acoustic holograms, or holographic acoustic lenses, which allow for more refined control over the spatial structure of the acoustic field. These technological advancements hold the promise of enhancing FUS by improving the accuracy of acoustic field localization and providing a more cost-effective solution compared to conventional systems like phased array transducers. However, the accuracy and applicability of existing models and techniques are constrained by assumptions, including the uniformity of the propagation medium and the linearity of the acoustic field, which limits the functionality and restricts the potential applications of acoustic holograms. In this dissertation, we present novel numerical techniques, algorithms, and proof-of-concept experiments to fill those knowledge gaps and expand the functionality of acoustic holograms in crucial applications.

Laser-plasma-based ion accelerators are becoming a versatile platform to drive different fields of applied research and life sciences, for example translational research in radiation oncology. To ensure stable accelerator performance, complete control over the ion source, i.e., the high-intensity laser-solid interaction, is required. However, idealized interaction conditions are almost impossible to reach, as the utilized high-power lasers always feature a non-negligible amount of light preceding the laser peak. This leading edge of the laser pulse usually exceeds the ionization potential of bound electrons much earlier than the arrival of the high-power laser peak and the solid-density target undergoes significant modifications even before the actual high-intensity laser-plasma interaction starts. Control over this so-called target pre-expansion is a key requirement to achieve quantitative agreement between numerical simulations and experiments of high-intensity laser-solid interactions. This thesis investigates several aspects that are relevant to improve the capability of simulations to model realistic experimental scenarios. The corresponding experiments are conducted with cryogenic hydrogen-jet targets and the DRACO-PW laser at peak intensities between 10^12 W/cm^2 and 10^21 W/cm^2 . The experimental implementation of time-resolved optical-probing diagnostics and technical innovations with respect to the technique of off-harmonic optical probing overcome the disturbances by parasitic plasma self-emission and allow for unprecedented observations of the target evolution during the laser-target interactions. The laser-induced breakdown of solids, i.e., the phase transition from the solid to the plasma state, can be considered as an heuristic starting point of high-intensity laser-solid interactions. As it is highly relevant to simulations of target pre-expansion, Chapter 3 of this thesis presents time-resolved measurements of laser-induced breakdown in laser-target interactions at peak intensities between 0.6 * 10^21 W/cm^2 and 5.7 * 10^21 W/cm^2 . By increasing the peak intensity, a lowering of the applicable threshold intensity of laser-induced breakdown well below the appearance intensity of barrier-suppression ionization occurs. The observation demonstrates the relevance of the pulse-duration dependence of laser-induced breakdown and laser-induced damage threshold to the starting point of high-intensity laser-solid interactions. To apply the results to other laser-target assemblies, we provide a detailed instruction of how to pinpoint the starting point by comparing measurements of the laser contrast with a characterization study of the target-specific thresholds of laser-induced breakdown at low laser intensity. Chapter 4 of this thesis presents an example of how optical-probing diagnostics are able to estimate target pre-expansion as a starting condition for particle-in-cell simulations. The measurement allows to restrict the surface gradient of the pre-expanded plasma density to an exponential scalelength between 0.06 um and 0.13 um. Furthermore, the plasma-expansion dynamics induced by the ultra-relativistic laser peak are computed and post-processed by ray-tracing simulations. A comparison to the experimental results yields that the formation of the measured shadowgrams is governed by refraction in the plasma-density gradients and that the observed volumetric transparency of the target at 1.4 ps after the laser peak is not caused by relativistically induced transparency but by plasma expansion into vacuum instead.

Individuals with rheumatic diseases such as Osteoarthritis (OA), Rheumatoid Arthritis (RA) and axial Spondyloarthritis (axSpA) usually are less physically active and engage in low-intensity training. Pain and function impairment lead to reduction in their quality of life. Evidence prove High-Intensity Training (HIT) can positively impact pain and function, however, usually neglected. Assessing the previous research and addressing knowledge gaps in this area can lead to more beneficial intervention to improve the overall quality of life among these populations. HIT is a beneficial and promising approach in most situations to managing symptoms including pain and function in individuals with OA, RA, and axSpA. However, contradictory results arise the need for further meticulous and high-quality studies in this area.