京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第18790号 / 理博第4048号 / 新制||理||1582(附属図書館) / 31741 / 京都大学大学院理学研究科物理学・宇宙物理学専攻 / (主査)教授 中村 卓史, 教授 鶴 剛, 教授 田中 貴浩 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

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Chronic ankle instability (CAI), a pathological condition characterized by repetitive bouts of the ankle giving way, commonly develops following a lateral ankle sprain injury. Individuals with CAI have been shown to exhibit deficits in postural control and alterations in movement dynamics, which have been suggested to be contributing factors to the recurrent injury paradigm. The purpose of this investigation was to conduct a comprehensive biomechanical analyses to examine the influence of CAI on postural control and movement dynamics during a single leg squat, side-cut task, and single leg landing on an inverted surface. Fifteen participants with CAI and fifteen participants without CAI completed the study following a between-subjects design, with limb serving as the repeated measure during the single leg squat. Each participant completed a single leg squat, side-cut task, and unexpected and expected single leg landings on a tilted surface. Results from the single leg squat and single leg landings on the tilted surface were analyzed using a 2 x 2 mixed-model ANOVA, while results from the side-cut task were analyzed using an independent samples t-test. Statistical significance was considered for all dependent variables when p < 0.05. Individuals with CAI demonstrated impaired postural control, as indicated by reduced time-to-boundary, during the single leg squat compared to controls. Altered ankle joint kinetics and increased sagittal plane hip joint stiffness were observed in the CAI group compared to controls. With regards to the single leg landings on the inverted surface, during the unexpected landing condition the CAI group displayed altered neuromuscular control and ankle kinematics. However, when the landing on the inverted surface as expected, the CAI group exhibited similar motor control strategies to the control group. Findings from this study indicate CAI alters postural control and movement dynamics during functional and dynamic movements, which may be used by researchers and clinicians to develop rehabilitation protocols to restore maladaptive movement patterns in individuals that develop CAI.

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Oxidative stress (OS) occurs when DNA repair mechanisms are overcome by the amount of single and double strand DNA breaks caused by an accumulation of reactive oxygen species (ROS). Genomic instability (GI) by microsatellite instability (MSI) accumulation is characterized by changes in DNA single tandem repeats (STR) as a direct result of ROS. Deregulation of DNA repair and tumor suppressor pathways have been described as causes of tumor progression and metastasis. Studies in mammals have focused on GI and the implications of increased mutation frequency due to accumulation of MSI leading to development of diseases, including infertility and cancer. Ovarian cancer is a deadly disease displaying the highest mortality rate among gynecological cancers. Hereditary ovarian cancer displays GI that can be established early in primordial germinal cells (PCGs) development and migration across the genital ridge, where PGCs are exposed to ROS damage. The hypothesis of this study was ROS-induced GI is marked by the accumulation of MSI on repetitive sequences of DNA that override DNA repair, tumor suppressor and redox homeostasis pathways. In this study, we induced ROS in human ovarian cell lines by hydrogen peroxide (H2O2) exposure, as well as evaluated mouse PGCs to determine whether MSI occurs in specific regions of human and mouse genomes. Our results show that MSI was present in specific markers after ROS-induced damage in human ovarian cells and in mouse Sod1 knockout PGCs during cell migration, both of which accumulate specific mutations caused by free radical damage. Ovarian tumor cells and mouse PGCs showed an increase of MSI in 12 human and 5 mouse repetitive markers that are located near important genes related to DNA repair, tumor suppression, cell proliferation, apoptosis and differentiation. This could be a signal that leads to tumor initiation, formation and progression in adult ovarian cells due to improper DNA repair and tumor suppression mechanisms or in disruption of PGC migration that determines germinal cell pool selection during early embryonic development due to absence of cell antioxidant mechanisms. Therefore, these specific unstable STRs are novel biomarkers that could be useful in early diagnostics, prognosis, and successful therapy of ovarian tumorigenesis.

Glioblastoma multiforme (GBM) is an extremely aggressive and almost always fatal brain tumor. GBM literature indicates defective mismatch repair (MMR) mechanisms are not involved in GBM tumorigenesis as in other tumors, and instigating mechanisms of GBM tumorigenesis remain unclear. GBM and neural progenitor (NPR) cells were exposed to three concentrations of H2O2 (0, 0.5, and 1.0 μM), cultured, and then harvested 0, 2, 4, and 6 days post-exposure; DNA from cells was amplified with microsatellite primers, investigating whether or not H2O2 exposure affected microsatellite instability (MSI) in target sequences. Three out of six markers showed significant MSI in the H2O2-exposed NPR cells. Our results suggest H2O2, which generates reactive oxygen species (ROS), correlated with MSI accumulation that occurred in NPR cells in specific DNA regions. Thus, gene expression analysis to assess normal and abnormal gene expression of GBM and NPR cellss is warranted.

BACKGROUND: Whole body vibration (WBV) platforms are currently used as adjunctive training devices for exercise programs, and have been shown to facilitate flexibility. One of the biggest contributing factors to chronic ankle instability (CAI) is the lack of dorsiflexion after lateral ankle sprains and WBV may be an effective way to increase range of motion in this population. PURPOSE: Determine if WBV done concurrently with static stretching (SS) is more effective then SS alone in improving dorsiflexion ROM in subjects with CAI. METHODS: Subjects were divided into 3 groups (control, static stretch, and static stretch and vibrate). Subjects stretched 4 days/wk for 3 wks for 4 sets of 30 seconds alternating 2 different positions to stretch both the soleus and the gastrocnemius. Imposed vibration at 34 Hz 2mm during the stretches for the stretch group. ANALYSIS: Repeated measures ANOVA was performed using SPSS (version 19), with post-hoc Tukey tests as needed (p<.05). RESULTS: In both the straight and bent leg position, a significant group x time interaction was found for dorsiflexion range of motion. Post hoc tests revealed significance in the SV group between pre-tx and post-tx 1 and pre-tx and post-tx 2. No statistical significance was found between post-tx 1 and post-tx 2 in the SV group or at any time in the N or SS group. DISCUSSION: Static Stretching with vibration increases dorsiflexion ROM in subjects with CAI better than static stretching alone.

This thesis describes the development, verification, and validation of a three dimensional time domain thermoacoustic solver. The purpose of the solver is to predict the frequencies, modeshapes, linear growth rates, and limit cycle amplitudes for combustion instability modes in gas turbine combustion chambers. The linearized Euler equations with nonlinear heat release source terms are solved using the finite volume method. The treatment of mean density gradients was found to be vital to the success of frequency and modeshape predictions due to the sharp density gradients that occur across deflagration waves. In order to treat mean density gradients with physical fidelity, a non-conservative finite volume method based on the wave propagation approach to the Riemann problem is applied. For modelling unsteady heat release, user input flexibility is maximized using a virtual class hierarchy within the OpenFOAM C++ library. Unsteady heat release based on time lag models are demonstrated. The solver gives accurate solutions compared with analytical methods for one-dimensional cases involving mean density gradients, cross-sectional area changes, uniform mean flow, arbitrary impedance boundary conditions, and unsteady heat release in a one-dimensional Rijke tube. The solver predicted resonant frequencies within 1% of the analytical solution for these verification cases, with the dominant component of the error coming from the finite time interval over which the simulation is performed. The linear iii growth rates predicted by the solver for the Rijke tube verification were within 5% of the theoretical values, provided that numerical dissipation effects were controlled. Finally, the solver is then used to predict the frequencies and limit cycle amplitudes for two lab scale experiments in which detailed acoustics data are available for comparison. For experiments at the University of Melbourne, an empirical flame describing function was provided. The present simulation code predicted a limit cycle of 0.21 times the mean pressure, which was in close agreement with the estimate of 0.25 from the experimental data. The experiments at Purdue University do not yet have an empirical flame model, so a general vortex-shedding model is proposed on physical grounds. It is shown that the coefficients of the model can be tuned to match the limit cycle amplitude of the 2L mode from the experiment with the same accuracy as the Melbourne case. The code did not predict the excitation of the 4L mode, therefore it is concluded that the vortex-shedding model is not sufficient and must be supplemented with additional heat release models to capture the entirety of the physics for this experiment.