Acoustic emission (AE) is a natural phenomenon that occurs when a solid is subjected to stress. These emissions are produced by all materials during pre failure. In soil, AE results from the release of energy as particles undergo small strains. If these emissions can be detected, then it becomes possible to develop an early warning system to predict slope failure. International research has shown that AE can be used to detect ground deformations earlier than traditional techniques, and thus it has a role to play in reducing risk to humans, property and in mitigating such risks. This thesis researches the design of a system to quantify the AE and calculate the distance to the deformation zone, and hence information on the mechanism of movement. The quantification of AE is derived from measuring the AE event rate, the output of which takes the form of a displacement rate. This is accurate to an order of magnitude, in line with current standards for classifying slope movements The system also demonstrates great sensitivity to changes within the displacement rate by an order of magnitude, making the technique suitable to remediation monitoring. Knowledge of the position of the shear surface is critical to the planning of cost effective stabllisation measures. This thesis details the development of a single sensor source location technique used to obtain the depth of a developing or existing shear surface within a slope. The active waveguide is used to reduce attenuation by taking advantage of the relatively low attenuation of metals such as steel. A method of source location based on the analysis of Lamb wave mode arrival times at a smgle sensor is summansed. An automatic approach to source location is demonstrated to locate a regular AE source to within one metre. Overall consideration is also given to field trials and towards the production of monitoring protocols for data analysis, and the implementation of necessary emergency/remediation plans.

Combustion instabilities (thermo-acoustic pressure oscillations) have been recognised for some time as a problem limiting the development of low emissions (e.g., lean burn) gas turbine combustion systems, particularly for aviation propulsion applications. Recently, significant research efforts have been focused on acoustic damping for suppression of combustion instability. Most of this work has either been experimental or based on linear acoustic theory. The last 3-5 years has seen application of density based CFD methods to this problem, but no attempts to use pressure-based CFD methods which are much more commonly used in combustion predictions. The goal of the present work is therefore to develop a pressure-based CFD algorithm in order to predict accurately acoustic propagation and acoustic damping processes, as relevant to gas turbine combustors. The developed computational algorithm described in this thesis is based on the classical pressure-correction approach, which was modified to allow fluid density variation as a function of pressure in order to simulate acoustic phenomena, which are fundamentally compressible in nature. The fact that the overall flow Mach number of relevance was likely to be low ( mildly compressible flow) also influenced the chosen methodology. For accurate capture of acoustic wave propagation at minimum grid resolution and avoiding excessive numerical smearing/dispersion, a fifth order accurate Weighted Essentially Non-Oscillatory scheme (WENO) was introduced. Characteristic-based boundary conditions were incorporated to enable accurate representation of acoustic excitation (e.g. via a loudspeaker or siren) as well as enable precise evaluation of acoustic reflection and transmission coefficients. The new methodology was first validated against simple (1D and 2D) but well proven test cases for wave propagation and demonstrated low numerical diffusion/dispersion. The proper incorporation of Characteristic-based boundary conditions was validated by comparison against classical linear acoustic analysis of acoustic and entropy waves in quasi-1D variable area duct flows. The developed method was then applied to the prediction of experimental measurements of the acoustic absorption coefficient for a single round orifice flow. Excellent agreement with experimental data was obtained in both linear and non-linear regimes. Analysis of predicted flow fields both with and without bias flow showed that non-linear acoustic behavior occurred when flow reversal begins inside the orifice. Finally, the method was applied to study acoustic excitation of combustor external aerodynamics using a pre-diffuser/dump diffuser geometry previously studied experimentally at Loughborough University and showed the significance of boundary conditions and shear layer instability to produce a sustained pressure fluctuation in the external aerodynamics.

The pedunculopontine nucleus (PPN) is a reticular collection of neurons at the junction of midbrain and pons. The PPN in animal models appears topographically organised and functionally related to locomotion and arousal. In Parkinson’s disease, the PPN degenerates and is susceptible to abnormal basal ganglia output. In patients with Parkinson’s disease, low frequency PPN stimulation is proposed to improve gait freezing and postural instability. However, the therapeutic mechanisms, optimal clinical application and precise effects on gait and posture of PPN stimulation are unclear. Here, a topographic arrangement of the PPN was supported by local field potential recordings in parkinsonian patients. In the PPN region, beta oscillations were recorded rostrally and alpha oscillations caudally. Alpha oscillations, consistent with their putative role in allocating attention, correlated with gait performance and attenuated with gait freezing. Thus the caudal PPN subregion may be the most relevant target for gait disorders. Accordingly, an unblinded clinical study suggested that stimulation of the caudal PPN subregion was beneficial for gait freezing, postural instability and falls. In a double-blinded study using spatiotemporal gait analysis, caudal PPN stimulation reduced triggered gait freezing, with bilateral stimulation more effective than unilateral. However, akinesia including akinetic gait did not improve with PPN stimulation. Accordingly, dopaminergic medication requirements did not change. Mechanisms underlying gait freezing and PPN stimulation were explored with reaction time experiments. Parkinsonian patients with severe gait freezing and postural instability demonstrated a ‘block’ to pre-programmed movement. This was evidenced by prolonged simple reaction times and the absence of ‘StartReact’, whereby pre-prepared responses are normally accelerated by loud acoustic stimuli. PPN stimulation improved simple reaction time and restored Startreact. The relief of this ‘motor block’ with PPN stimulation may therefore explain the associated improvement in gait freezing and postural instability, as these tend to occur in circumstances requiring triggered, pre-prepared adjustments.

Submitted in partial compliance with the requirements for the Master’s Degree in Technology: Chiropractic, Durban University of Technology, Durban, South Africa, 2016. / Purpose: Ankle sprains are amongst the most common injury sustained by athletes and the general public. When an ankle is repeatedly sprained it results in chronic ankle instability syndrome (CAIS). This repeated trauma results in disruption of the afferent nerve supply from the injured joint, which affects the motor neuron pool excitability of the peroneal and soleus muscles resulting in arthogenic muscle inhibition (AMI). Traditional treatment for CAIS focuses on rehabilitation of the affected muscles via strength and proprioceptive training. Recent literature has shown that the addition of ankle joint manipulation resulted in improved clinical outcomes in the treatment of CAIS. The mechanism on how joint manipulation affects AMI is under-investigated especially in extremity joints. Thus this study aimed to determine the immediate effect of ankle joint manipulation on peroneal and soleus muscle activity, by assessing surface electromyography (sEMG) H/M ratio to detect a change in the proportion of the total motor neuron pool being recruited, in participants with CAIS. Methods: The study utilised a quantitative, experimental, pre-test post-test study design. Forty two participants with grade I and II CAIS, aged 18-45 years, were randomly allocated into one of three groups. Group one received a single talocrural joint long axis distraction manipulation, group two received a sham manipulation and group three was the control receiving no intervention. sEMG H/M ratio measurements were taken before and immediately after the intervention using a Biopac wireless emg system. Results: The groups were comparable at baseline for age, gender, body mass index and H/M ratio measurements for the soleus and peroneal muscles (p < 0.050). Intra-group analysis of the soleus muscle H/M ratio showed no statistically significant change over time for the manipulation (p = 0.975) and sham (p = 0.056) groups, with the control group showing a statistically significant (p = 0.019) decrease in the H/M ratio. For the peroneal muscle no statistically significant (p > 0.050) differences were observed in any of the three groups. Inter-group analysis of the soleus muscle H/M ratio measurements showed no statistically significant differences between the three groups (p = 0.470; F = 1.010) over time, with Tukey’s HSD post-hoc test revealing a statistically significant (p = 0.028) difference being observed between the sham and control groups in terms of post soleus muscle H/M ratio measurements. Conclusion: This study failed to show that ankle joint manipulation affects the soleus and peroneal muscles in terms of H/M ratio measurements in participants with CAIS. There may have been a trend of an effect of the sham and manipulation interventions counteracting the muscle fatigue experienced in the control group, however further investigation is required. / M

When damaged DNA is detected during replication, a checkpoint delays the cell cycle to allow time for repair. Here I show that continually delaying the cell cycle in the G2/M phase of the cell cycle stabilizes the genome of Saccharomyces cerevisiae in both checkpoint proficient and deficient cells; a phenomenon I call slow cycle stabilization (SCS). SCS stabilizes the genome in cells defective for DNA damage response (DDR), spindle checkpoint, and telomere biology, as well as wild type (WT) cells. I verify SCS using genetic and chemical means and further substantiate SCS using three different Saccharomyces cerevisiae chromosome systems.

Effective design of liquid fuel injection systems is a function of good understanding of liquid breakup mechanisms. A transient liquid breakup model is developed on the classical interfacial breakup theory by modifying the classical linear perturbation process to include time-dependent base and perturbed flow parameters. The non-isothermal condition on liquid jet instability and breakup is theoretically modelled; with the particular consideration of a spatially variation of surface tension along the liquid-gas interface. The model combines the classical interface hydrodynamic instability and breakup theory and heat-transfer through semi-infinite medium. Analytical liquid breakup model, which combines transient and non-isothermal effects on liquid jet breakup, is suggested. The suggested model could be simplified to the transient breakup model and the non-isothermal breakup model equivalents. A novel mechanistic model, which is based on a simple momentum balance between the injected jet and the aerodynamic drag force, is suggested for breakup length. A new model, which combines energy criterion and dual-timescale for turbulent shear in droplet dispersion, is suggested for droplet breakup criteria on the basis of critical Webber number. All developed models showed good predictions of available experimental data, and established empirical correlation, within the operational conditions of contemporary ICEs, specifically diesel engines. Continued research in these areas could benefit the development of the next generation of liquid fuel injectors and combustors – by accounting for transient effects and non-isothermal conditions in liquid jet breakup, and turbulent shear in droplet breakup.

Optimizing culture conditions that reduce genomic instability in human pluripotent stem cells (hPSCs) is an unmet challenge in the field. Results from our lab and numerous research groups demonstrate that hPSCs are prone to genomic aberrations and single-cell passaging increases the rate of genomic alterations. However, single-cell based passaging maintains advantages for scale-up and standardizing differentiation protocols. In this study, we investigated the problem of genomic instability in hPSC cultures with the goal towards identifying and characterizing candidate genes that could contribute to generation and survival of abnormal hPSCs. Based on microarray analysis, we identify ARHGDIA, located on 17q25, as a candidate gene conferring selective advantage to trisomy 17 hPSCs. Using lentiviral approaches to overexpress ARHGDIA in hPSCs, [hPSC (Arg)], we functionally validate that in enzymatically passaged co-cultures, hPSC (Arg) lines exhibit competitive advantage against wild type hPSCs, [hPSC (WT)]. Additionally, hPSC (Arg) lines exhibit increased single-cell survival at low density plating. In co-cultures with hPSC (WT), ROCKi exposure attenuated the competitive advantage of hPSC (Arg) subpopulations. For the first time, this work demonstrates that increased expression of a gene on 17q25 confers selective advantage to hPSCs. In parallel studies, using medium devoid of bFGF containing LIF plus two inhibitors, MEK inhibitor (PD0325901) and p38 inhibitor (SB203580), we demonstrate that hPSCs are LIF responsive and can be stably maintained in naive pluripotent culture conditions. Based on their clonal viability, we propose that naive hPSCs are a more genetically stable population than primed hPSCs, when passaged as single- cells. These studies will aid the long-term goal of hPSC scale-up while promoting stable propagation of genomically normal hPSCs.

Introduction: Following lateral ankle sprain, many individuals experience recurrent injury and symptoms of giving-way, known as Functional Ankle Instability (FAI). It has been proposed that altered joint kinematics during activity may contribute to instability in these individuals, however research findings have been inconsistent. Objective: To capture foot and ankle kinematic data during two common tasks (walking gait and jump landing) among three groups: individuals with FAI, healthy controls and copers. Design: 3-group observational cross-sectional study. Participants: Participants included 23 individuals with a history of ≥ 1 ankle sprain and at least 2 episodes of giving-way in the past year (FAI: M±SD; age=23.30±3.84years; height=1.71±0.11m, weight=68.66±14.60kg; Cumberland Ankle Instability Tool [CAIT]=20.52±2.94, episodes of giving-way=5.81±8.42 per month), 23 subjects with no history of ankle sprain or instability in their lifetime (Controls: age=23.17±4.01years, height=1.72±0.08m, weight=68.78± 13.26kg, CAIT: 28.78±1.78), and 23 individuals with a history of a single ankle sprain and no subsequent episodes of instability (Copers: age=23.52±3.68years, height=1.72±0.07m, weight=69.57±13.94kg; CAIT: 27.74 ± 1.69). Interventions: Ten trials of natural walking gait and 10 single leg drop jumps were recorded using a ViconMX motion monitoring system (OMG, Oxford, UK) and two imbedded force plates (Bertec, Columbus, Ohio, USA). Main Outcome Measures: Forefoot and hindfoot sagittal and frontal plane angles were calculated at initial contact (IC) and toe-off (TO) of walking gait, and IC and maximal vertical ground reaction force of jump landing. Results: At walking IC, there was a significant group difference in forefoot inversion (F2,66=4.68, p=0.013). Post hoc testing revealed that individuals with FAI were significantly more inverted than controls, but copers were not significantly different from the FAI or control groups. At jump landing IC, there were significant group differences in hindfoot motion (F2,66=6.12, p=0.004). Specifically, individuals with FAI were significantly more dorsiflexed than the control or coper groups. There were no other significant group differences (all p>0.05). Conclusions: Kinematic differences exist between healthy controls, copers and individuals with FAI. Copers and individuals with FAI have both experienced ankle sprain injury, yet copers do not experience subsequent instability. Analysis of coper movement patterns compared to control and FAI groups may provide insight into coping mechanisms.

Investigating the biological basis of ageing is both fascinating and medically relevant, as we strive to understand both how organisms age, and how our knowledge might be put to good use in an increasingly long-lived human population. Despite the complexity of ageing biology, it is very striking that longevity, in a wide variety of organisms, can be modified by manipulating single genes. In this thesis, I investigate phenotypes associated with mutations in C. elegans homologues of human WRN, the gene mutated in the progeroid Werner syndrome (WS). Mutant phenotypes in the worm recapitulate aspects of the pathophysiology observed in WS patients, including premature ageing, genomic instability, and sensitivity to DNA damaging agents. wrn-1 overexpression, on the other hand, appears to enhance longevity, suggesting that wrn-1 acts as a bona fide anti-gerontogene. The combination of wrn-1 mutations with mutation in the worm p53 homologue, cep-1, unexpectedly triggers a novel and very striking enhanced lifespan and healthspan phenotype, termed synthetic super-viability (SSV). The SSV phenotype is modulated by various environmental inputs such as temperature stress. The data presented here can be incorporated into a model in which stress sensing (involving p53) is the crucial determinant of longevity outcomes. Several theories of ageing incorporate the idea that 'that which does not kill us, makes us stronger' - encapsulated in a biological sense in the idea of hormesis, a physiological shift in response to stress. Here, this hypothesis is expanded to include the notion that intrinsic <strong>responses</strong> to stress may themselves act to limit lifespan - too much of a good thing can be bad.

La prédiction des instabilités fluide-élastique qui se développent dans un faisceau de tubes est importante pour la conception des générateurs de vapeur dans les centrales nucléaires, afin de prévenir les accidents liés à ces instabilités. En effet, ces instabilités fluide-élastique, ou flottements, conduisent à une fatigue vibratoire des matériaux, voire à des chocs entre les tubes, et par la suite, à des dégâts importants. Ces aspects sont d'une grande complexité pour les applications scientifiques impliquant l'industrie nucléaire. Le présent travail est issu d'une collaboration entre l'EDF, le CEA et l'IMFT. Elle vise à améliorer la simulation numérique de cette interaction fluide- structure dans le faisceau de tubes, en particulier dans la gamme de paramètres critiques favorisant l'apparition d'un amortissement négatif du système et de l'instabilité fluide-élastique. / The prediction of fluid-elastic instabilities that develop in a tube bundle is of major importance for the design of modern heat exchangers in nuclear reactors, to prevent accidents associated with such instabilities. The fluid-elastic instabilities, or flutter, cause material fatigue, shocks between beams and damage to the solid walls. These issues are very complex for scientific applications involving the nuclear industry. This work is a collaboration between EDF, CEA and IMFT. It aims to improve the numerical simulation of the fluid-structure interaction in the tube bundle, in particular in the range of critical parameters contribute to the onset of damping negative system and the fluid-elastic instability.