This thesis concerns the simulation of locomotion in vertebrates. The state-of-the-art uses genetic algorithms together with solid body kinematics to generate possible solutions for stable gaits. In recent work, this methodology led to a hopping gait in a dinosaur and the researchers wondered if this was realistic. The purpose of the research carried out in this thesis was to examine whether quick and simple finite-element analyses could be added to the simulator, to evaluate a simple ―break or―not break failure criterion. A break would rule out gaits that might damage theowner‘s skeleton. Linear elastic analysis was considered as a possible approach as it would add little overhead to the simulations. The author used X-ray computed tomography and the finite element method to examine the axial loading of a barnacle goose femur. The study considered four levels of detail for a linear elastic simulation, finding that all the analyses carried out overestimated the strength of the bone, when considering safety factors. The conclusion is that to incorporate stress-strain analysis into the gait simulation requires more realistic models of bone behaviour that incorporate the nonlinear response of bone to applied loading. A new study focusing on the use of novel techniques such as model order reduction is recommended for future work. The outputs of this research include chapters written up as journal papers covering a 4D tomography experiment; a level of detail study; an analysis of a purported tendon avulsion injury in Tyrannosaurus rex and a review of the elastic properties of bone.

Diplomová práca je zameraná na napäťovú a deformačnú analýzu elektricky vyhrievaného potrubia a príslušných častí. Cieľ práce je analýza častí potrubia samostatne a vo vzájomnom pôsobení voči medzným stavom, a zistenie maximálneho dovoleného zaťaženia. Potrubie je analyzované voči medznému stavu pružnosti a maximálnej dovolenej deformácií. Podpora je analyzovaná s cieľom nájsť adekvátne zaťaženia a silové reakcie počas inštalačnej fázy. Nakoniec je vyšetrované vzájomné pôsobenie. Potenciálne prekročenie daného medzného stavu je diskutované v adekvátnej kapitole.

Haemodialysis (HD) patients have a high mortality risk and most have echocardiographic evidence of abnormal cardiac structure or function. Markers, such as left ventricular hypertrophy (LVH), show association with adverse outcome in the general population and can aid in clinical decision making. The aim of this research was to explore the prognostic utility of established and novel two-dimensional (2DE) and three-dimensional transthoracic echocardiographic (RT3DE) techniques in HD patients. Adult maintenance HD patients from a single tertiary nephrology centre including satellite dialysis units were enrolled. Exclusion criteria were if patients were clinically unstable, unable to consent, or if required ambulance transportation for echocardiography visits. Consented patients underwent 2DE with speckle tracking (STE), RT3DE and VicorderTm measurements of pulse wave velocity (PWV) on a non-dialysis day, after the short inter-dialytic break. Clinical phenotype data, 3-month averaged blood results and dialysis prescriptions were obtained from the hospital electronic patient records. All patients screened were followed-up until death, renal transplantation, moving out of the region, or 16th November 2015. Regression analysis was used to assess the cross-sectional relationship between echocardiographic parameters. Relationship of echocardiographic parameters with outcome was assessed by Cox regression analysis. The first study explored whether patients recruited had similar characteristics and survival compared with patients who declined consent or who were excluded from the study. Patients who declined consent had an adjusted hazard ratio (HR) for all-cause mortality compared with recruited patients of 1.70, 95% confidence interval (CI) 1.10-2.52, and excluded patients had an adjusted HR of 1.30, 95% CI 0.75-2.25. Recruited patients may be a 'fitter' population and this needs to be considered when interpreting results. The second study reports that when global longitudinal strain (GLS) is combined in a multivariable model with PWV; PWV is superior to GLS in its association with mortality (adjusted HR 1.23, 95% CI 1.03-1.47 versus HR 1.00, 95% CI 0.86-1.17). When this analysis was repeated in a sub-group of patients with LVH, neither GLS nor PWV were associated with mortality, whilst both were prognostically significant in a preserved LVEF sub-group (PWV: HR 1.23, 95% CI 1.04-1.4 and GLS: HR 1.16, 95% CI 1.01-1.33). Therefore GLS has different prognostic implications in different patient sub-groups. The third study explored whether tissue motion mitral annular displacement (TMAD) measured by STE may be a more useful alternative to GLS as it measures strain but is quicker and less user-dependent. TMAD was closely correlated to GLS (r=-0.614, p<0.001), but had no prognostic power for mortality (adjusted HR 1.04,95% CI 0.91-1.19). The correlation between 2DE and RT3DE determined LV mass and volume measurements and the prognostic significance of RT3DE measurements were assessed. Although there was good correlation between 2DE and RT3DE LV volume measurements, 2DE overestimated LV mass compared to RT3DE. RT3DE measures gave no added prognostic value, and there were added difficulties in obtaining adequate images for RT3DE (35% of patients who had adequate 2D images). Furthermore, although RT3DE determined LV mechanical dyssynchrony index was prolonged in HD patients compared with published general population controls, it failed to show any prognostic significance (HR 2.16, 95% CI 0.96-4.89) for mortality, but was associated with hospitalisation for heart failure (HR 1.03, 95% CI 1.00-1.06). These results indicate that novel measurements of sub-clinical cardiac dysfunction have the potential to aid prognostication in this high risk population. Follow-up studies exploring the longitudinal change in these parameters is ongoing.

The Achilles tendon is the largest tendon in the human body, which elastically stores and releases energy to facilitate walking and running. Tendons can suffer from a range of pathologies, most notably that of complete rupture, which affects athletes, physically active workers and the aged. There is a growing demand for in vivo methods of objectively measuring tendon health for aiding diagnosis, monitoring therapy and for assessment of new treatments. Knowledge of the changes in mechanical properties during the healing process is also limited and new methods to accurately and consistently estimate these could provide insights into the healing process and guide future research efforts. This thesis presents the development and use of 2D ultrasound elastography, a quantitative strain estimation imaging technique, as a tool to measure changes in the tensile mechanical properties of the Achilles tendon. This technique performs frame-to-frame block matching of image texture to track motion in an ultrasound signal sequence and create a strain estimation field from the spatial derivative of the motion. Elastography in the image-lateral direction of sagittal plane scans is of particular interest as this is in line with the longitudinal axis of the tendon, but presents extra accuracy issues from out of plane motion and lower image spatial resolution. Tendon rupture also presents unique problems to image acquisition and analysis- patient pain and safety are important considerations and disruption of the ultrasound texture can make 2D motion tracking more difficult. A new 2D elastography block matching algorithm, named `AutoQual', was developed to enable accurate tracking of motion in the image-lateral direction and reduce the impact of artefacts and errors common with damaged Achilles tendons image sequences. It was shown to outperform a multiscale block matching method when tested using ultrasound sequences from in vivo and gelatine phantom experiments. The input parameters of this algorithm were then optimised using the phantom data for benchmarking. The AutoQual algorithm was then used to analyse ultrasound sequences from a 24-week longitudinal study of 21 subjects with ruptured Achilles tendons to assess lateral, axial and principal strains during controlled passive motion of the foot or axial palpation of the ultrasound probe. Lateral and principal strains from controlled dorsiflexion were shown to be more repeatable and more sensitive to change than axial strains with manual palpation. This experience with lateral strain imaging from ruptured Achilles tendons gave an increased knowledge of the strain imaging artefacts and features that can occur. These are described in detail in order that they may be further mitigated in quantitative analysis by optimising acquisition protocols, further amendment of the block tracking algorithm, or exclusion of erroneous areas when selecting regions of interest. Regularisation is a potential solution to some common artefacts such as discontinuities from poor tracking in shadow regions. Regularisation of the lateral displacement fields is investigated using 2D bicubic smoothing splines. The regularisation parameters used are shown to have minimal effect on quantitative analysis and can aid visual clarity or reduce artefacts within certain settings. However, regularisation was also shown to cause large errors when parameters were set more aggressively. Finally, it is identified that cumulative lateral strain measurement of the Achilles and other tendons is feasible but that future work is needed to further improve the quality of force and cross sectional area measurements in order to infer mechanical properties accurately. Repeatable high force motion protocols also need to be developed to measure healthy tendons and to ensure comparable results between different patients and research groups.

Polypeptides are polymerized chains of amino acids linked covalently through peptide bonds. Polyelectrolyte polypeptides are polypeptides with electrolyte repeating groups. Several amino acids contain ionizable side chains which result in charge distributions when dissolved in aqueous solutions. This dissertation is motivated by a desire to gain knowledge of polyelectrolyte polypeptides as recent advances in chemical synthesis of polypeptides have made possible the fabrication of designed polypeptides that do not naturally occur in nature. Potential applications of newly designed polypeptides span the range from medical to clothing and energy even to robotics. In this dissertation we compare the characteristic behavior of two polypeptide polyanions: Poly-(L-Glutamic Acid) [PLE] and Poly-(L-Glutamic Acid4, Tyrosine1) [PLEY(4:1)]. Comparative characteristic behaviors of each is conducted through relaxation phenomena in the context of mechanical elasticity measurements of hydrogels and dielectric relaxation of aqueous solutions in a radio frequency range of 1 MHz to 1000 MHz. Hydrogels are fabricated by crosslinking each polyanion with Poly-(L-Lysine) [PLK], a polycation, via the crosslinker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). Elasticity and viscoelasticity measurements are conducted in a fixture designed by our lab. Dielectric relaxation behavior is studied on aqueous solution of both PLEY and PLE using a capacitive fixture, also designed in our lab. RF signals provided by an impedance analyzer are converted to permittivity and dielectric loss measurements. Peaks in dielectric loss provide evidence of relaxation mechanisms. A comparison of experimental results to theoretical expectations reveal both expected and some surprising behavior. Relaxation times for crosslinked hydro-gels scale according to theoretical expectations according to so-called reptation dynamics. However, relaxation times of aqueous solutions did not scale as entangled polyelectrolytes. First, both PLEY and PLE scaled as neutral polymers rather than polyelectrolytes. This was expected because of the high concentrations studied. However, due to the high concentrations, it was expected that polypeptides were entangled in solutions. Data compared to theory did not support this expectation. We, additionally, conducted a self-crosslinking experiment of a polyampholyte: RADA16. RADA16 is known to self-assemble into nano-fibers formed by -sheet stacking. The self-crosslinking was also mediated by EDC. Results of crosslinking showed formation of polypeptide spherules as well as nano-crystals nominally orthorhombic in shape. It was not possible to ascertain composition of the nano-crystals due to both the limited amount of raw material available and the capabilities of measurement equipment as of this writing. It is hypothesized that nano-crystals are composed of some type of urea by-product from the crosslinking reaction. The spherules, on the other hand, seem to be described by the theory of hydrophobic polyelectrolytes. Additional research conducted with regards to electromagnetic hydrodynamic flows during the time frame of this dissertation is also included. The research uses hydrodynamic conservation equations as a starting point to derive one electromagnetic flow momentum equation analogous to the Cauchy momentum equation of hydrodynamics. It also introduces a mass- energy conservation equation for electromagnetic flow that has no hydrodynamic analogue. We begin this dissertation by introducing in Chapter 1 some of the theoretical background necessary to understand results from experiments. Chapter 2 introduces experimental results from elasticity and viscoelasticity measurements and Chapter 3 explains the dielectric relaxation experiment. We then follow with Chapter 4 which presents conclusions from mechanical and dielectric relaxation experiments in a concise format. Results from the self- crosslinking of RADA16 are presented in Chapter 5. Finally, the additional research on electromagnetic flow is presented in Chapter 6.

Master of Science / Department of Clinical Sciences / Walter C. Renberg / Objective: To measure strain in vivo in the calcanean tendon during trotting in canines, and to compare to strain present after tibiotarsal immobilization. Animals: 6 canines Procedures: A Differential Variable Reluctance Transducer[superscript]TM (DVRT®) strain gauge was surgically implanted on the common gastrocnemius tendon. Surface EMG, % strain, and ground reaction forces were measured prior to intervention and after immobilization. Peak vertical force (Fz), vertical impulse, initial, maximum and final strain, and peak-to-peak EMG amplitude were recorded. Data was analyzed using repeated measures analysis of variance and paired t-tests (p[equal to or less than]0.05). Results: Timing of strain data correlated closely to the hind limb footstrike and EMG activity in all dogs. Maximum tendon strain occurred simultaneous with peak Fz. Continued muscle contraction was evident after immobilization. There was no statistical difference in maximum strain after immobilization compared to normal motion. Minimum strain, both at the beginning and end of the strain curve, was significantly decreased with the immobilized state compared to non-immobilized joints. Conclusions and Clinical Relevance: Tibiotarsal immobilization did not eliminate calcaneal tendon strain during weight bearing. Decreased isometric muscle contraction during swing phase of the gait would account for smaller minimum strain in immobilized joints. Immobilization is frequently applied after Achilles tendon rupture to alleviate strain and force on the sutured repair, with possible complications due to the immobilization method. Direct correlation of strain with tendon force was not made in this study. This would be an important factor before adjusting current treatment recommendations.

The Intervertebral disc (IVD), comprised of two distinct regions, namely the fibrous annulus fibrosus (AF) and the gelatinous nucleus pulposus (NP), is a fibrocartilage pad located between adjoining vertebrae of the spine. The function of the IVD is to provide stability to the spine, while maintaining movement. IVD degeneration, also known as degenerative disc disease (DDD), is the process whereby the IVD tissue degrades, resulting in loss of function to the disc. Low back pain (LBP) is associated with the degeneration of the IVD, making it important to investigate the pathogenesis of DDD, as this could lead to novel therapies for the prevention and/or treatment of LBP. Mechanical stimuli (MS) are known to be important for IVD cell matrix homeostasis, with cells of the AF and NP responding to physiological forces with a trend towards increased matrix anabolism, while non-physiological forces lead to matrix catabolism. Furthermore, recent evidence suggests that IVD cells derived from degenerate tissue may have lost their ability to respond to physiological MS in the 'normal' anabolic manner, potentially leading to the progression of DDD. It is therefore important to investigate the response of IVD cells derived from both non-degenerate and degenerate tissue to MS, to ascertain whether there is a difference with degeneration. If the response is found to be altered with degeneration, then elucidation of the potentially altered mechanotransduction pathway utilised by degenerate cells could lead to the discovery of novel therapeutic targets for the treatment of DDD. To date, the majority of IVD MS studies have concentrated on the response of NP cells to hydrostatic pressure, with only a limited number of AF studies available. Thus, the first aim of this PhD was to investigate the response of human AF cells derived from non-degenerate and degenerate IVDs to the physiologically relevant mechanical stimulus of cyclic tensile strain (CTS), to ascertain whether the response (regulation of matrix protein and matrix degrading enzyme gene expression) was frequency-dependent or altered with IVD degeneration. Using an in vitro mechanical loading system (Flexcell® Tension Plus™ system, Flexcell International) capable of delivering a CTS of 10% strain, 0.33Hz or 1.0Hz for 20 minutes, the response of AF cells derived from non-degenerate IVDs was found to be frequency-dependent (reduced catabolism at 1.0Hz, with decreased MMP -3 and ADAM-TS -4 gene expression; and catabolic at 0.33Hz, with decreased types I and II collagen and increased MMP -9 gene expression). Furthermore, the response of AF cells to 1.0Hz CTS was shown to be altered with IVD degeneration, depicted by a switch from reduced catabolism (decreased MMP -3 and ADAM-TS -4) in non-degenerate AF cells, to reduced anabolism (decreased aggrecan and type I collagen gene expression) in degenerate AF cells. Subsequently, the second aim of the PhD was to attempt to elucidate the mechanotransduction pathways operating in human AF cells derived from non-degenerate and degenerate IVDs, to ascertain whether the mechanotransduction pathway was altered with IVD degeneration. An identical mechanical stimulation regime was used (1.0Hz CTS) in parallel with functional inhibitors against the cytokines interleukin (IL) -1 and -4, and the cell surface receptors, RGD-recognising integrins. Additionally, the involvement of the cytokine associated transcription factors, nuclear factor kappa beta (NFκB) and signal transducer and activator of transcription (STAT) -6, as well as the integrin-associated kinase, focal adhesion kinase (FAK) was investigated in 1.0Hz CTS-treated non-degenerate AF cells. The response to 1.0Hz CTS (reduced catabolism) of AF cells derived from non-degenerate IVDs occurred in an IL -1, IL -4 and RGD-recognising integrin-dependent manner, with FAK being phosphorylated. Of significant interest, the altered response of AF cells derived from degenerate IVDs to 1.0Hz CTS (reduced anabolism) occurred independently of either cytokine and independently of RGD-recognising integrins, suggesting an altered mechanotransduction pathway in operation and warranting further investigation.

The examination of Workplace Aggression as a global construct conceptualization has gained considerable attention over the past few years as organizations work to better understand and address the occurrence and consequences of this challenging construct. The purpose of this dissertation is to build on previous efforts to validate the appropriateness and usefulness of a global conceptualization of the workplace aggression construct. This dissertation has been broken up into two parts: Part 1 utilized a Confirmatory Factor Analysis approach in order to assess the existence of workplace aggression as a global construct; Part 2 utilized a series of correlational analyses to examine the relationship between a selection of commonly experienced individual strain based outcomes and the global construct conceptualization assessed in Part 1. Participants were a diverse sample of 219 working individuals from Amazon’s Mechanical Turk participant pool. Results of Part 1 did not show support for a one-factor global construct conceptualization of the workplace aggression construct. However, support was shown for a higher-order five-factor model of the construct, suggesting that it may be possible to conceptualize workplace aggression as an overarching construct that is made up of separate workplace aggression constructs. Results of Part 2 showed support for the relationships between an existing global construct workplace aggression conceptualization and a series of strain-based outcomes. Utilizing correlational analyses, additional post-hoc analyses showed that individual factors such as emotional intelligence and personality are related to the experience of workplace aggression. Further, utilizing moderated regression analysis, the results demonstrated that individuals experiencing high levels of workplace aggression reported higher job satisfaction when they felt strongly that the aggressive act was highly visible, and similarly, when they felt that there was a clear intent to cause harm. Overall, the findings of this dissertation do support the need for a simplification of its current state of measurement. Future research should continue to examine workplace aggression in an effort to shed additional light on the structure and usefulness of this complex construct.

The examination of Workplace Aggression as a global construct conceptualization has gained considerable attention over the past few years as organizations work to better understand and address the occurrence and consequences of this challenging construct. The purpose of this dissertation is to build on previous efforts to validate the appropriateness and usefulness of a global conceptualization of the workplace aggression construct. This dissertation has been broken up into two parts: Part 1 utilized a Confirmatory Factor Analysis approach in order to assess the existence of workplace aggression as a global construct; Part 2 utilized a series of correlational analyses to examine the relationship between a selection of commonly experienced individual strain based outcomes and the global construct conceptualization assessed in Part 1. Participants were a diverse sample of 219 working individuals from Amazon’s Mechanical Turk participant pool. Results of Part 1 did not show support for a one-factor global construct conceptualization of the workplace aggression construct. However, support was shown for a higher-order five-factor model of the construct, suggesting that it may be possible to conceptualize workplace aggression as an overarching construct that is made up of separate workplace aggression constructs. Results of Part 2 showed support for the relationships between an existing global construct workplace aggression conceptualization and a series of strain-based outcomes. Utilizing correlational analyses, additional post-hoc analyses showed that individual factors such as emotional intelligence and personality are related to the experience of workplace aggression. Further, utilizing moderated regression analysis, the results demonstrated that individuals experiencing high levels of workplace aggression reported higher job satisfaction when they felt strongly that the aggressive act was highly visible, and similarly, when they felt that there was a clear intent to cause harm. Overall, the findings of this dissertation do support the need for a simplification of its current state of measurement. Future research should continue to examine workplace aggression in an effort to shed additional light on the structure and usefulness of this complex construct.

Fiber optic sensors are designed to measure various parameters. The distributed fiber optics sensor has been a very promising candidate for the structural health monitoring. In this thesis, we characterized LEAF (Large Effective Area Fiber) fiber’s Brillouin scattering spectrum and investigated its potentiality for the distributed Brillouin temperature and strain sensor. Optical fibers with complex refractive index profiles are applied to improve the Brillouin threshold by varying the Brillouin linewidth. As LEAF fiber has a modified refractive index profile, we investigated its Brillouin linewidth’s dependence on the square of the pump light’s frequency. We verified the Brillouin frequency’s variation with input SOP experimentally for LEAF fiber in the spontaneous regime. This sets a limitation for the frequency resolution of distributed Brillouin sensors. We also realized a simultaneous temperature and strain sensor with LEAF fiber applying the Brillouin optical time domain analysis. Based on the direct detection of LEAF beat frequencies, a simultaneous strain and temperature sensor was demonstrated.