Thesis (Ph. D.)--University of California, San Diego, 2000. / Vita. Includes bibliographical references (leaves 104-107).

Thesis (M.Eng.) -- Memorial University of Newfoundland. / Bibliography : leaves 89-91. Also available online.

Thesis (M.Sc.)--Memorial University of Newfoundland. / Typescript. Bibliography: leaves 83-86. Also available online.

Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Includes bibliographical references (p. 175-180).

Individuals with stroke have neuromuscular weakness or paralysis on one side of the body caused by some muscles disengaging and overexciting other muscles. Hyperextension of the knee joint and complete lack of plantar flexion of the ankle joint are common symptoms of stroke. This thesis encompasses the simulation of hemiparetic function using both a knee orthosis with variable impedance, specifically in terms of stiffness and damping, and the Proprioception Interference Apparatus. The section regarding the knee orthosis with variable impedance focuses on the creation and implementation of a small, lightweight, and adjustable orthotic device to be positioned around the knee of an able-bodied person to simulate hemiparetic gait. Force and range of motion data from able-bodied subjects fitted with the orthosis, inducing hemiparetic gait, was collected using the Computer Assisted Rehabilitation ENvironment (CAREN) system. The four parameters that the design focused on are damping, catch, hysteresis, and stiffness. The main goal of the project was to discern whether this device could be utilized as a viable research instrument to simulate hemiparetic gait. It was hypothesized that the device has the potential to be utilized in the future as a research device to be used on able-bodied persons to study asymmetries in gait and eventually quantify the Modified Ashworth Scale. It was also believed that it could serve as a possible rehabilitation device for people with stroke since it has been designed to induce larger knee flexion as an after effect. However, this would require the proper clinical evaluation and experimentation procedures to be successfully concluded. A comparison between how the dominant leg was affected by the orthosis and how the non-dominant leg was affected was investigated as well. The results show that the device affected the velocities, knee angles, and force profiles of the subject’s gait. The second section involving the Proprioception Interference Apparatus involved the creation and implementation of a haptic apparatus that utilizes vibration as well as transcutaneous electrical nerve stimulation (TENS) in various combinations with and without visual feedback to induce a proprioceptive illusion around the knee joint, as if a subject has a version of hemiparesis. The main goal of the project was to discern whether a device of relatively the same design could be utilized as a viable research instrument to simulate stroke-like balance in able-bodied subjects. Comparison between how the root mean square (RMS) values of each marker location, the average of the standard deviations of the forces, and RMS of the center of pressure affected the various conditions was investigated as well. It was hypothesized and concluded that the RMS values and average of the standard deviations when subjects had no visual feedback would have a significant difference from when they had visual feedback. It was also hypothesized that Proprioceptive Interference Apparatus (PIA) would have a significant effect on the RMS and standard deviation values since it was meant to disrupt the motor control function of the knee, however, this was proved false after data analysis. It was also surmised that the application of the TENS had more of an effect on the RMS and standard deviation values, whether it was used on its own or in combination with the vibrations, than the vibration stimulation alone. However, once again, this was not statistically significant.

No description available.

No description available.

A system with hysteresis is one that exhibits path dependent but rate independent memory. Hysteresis can be observed physically through the magnetization of a ferromagnetic material. In order to mathematically describe systems with hysteresis, we use the Preisach model. A discussion of the Preisach model is given as well as a method for computing the hysteretic transformation of an input variable. The focus of this paper is hysteresis in economics, namely, unemployment. We consider essential time series techniques for analyzing time series data, i.e. unit root testing for stationarity. However, we point out problems in modeling hysteresis with these techniques and argue that unit root tests cannot capture the selective memory of a system with hysteresis. For that, hysteresis in economic time series data is modeled using the Preisach model. We test the explanatory power of the previous unemployment rate on the current unemployment rate using both a hysteretic and non-hysteretic model. We find that the non-hysteretic model is better at explaining current unemployment rates, which suggests hysteresis is not present in the United States unemployment rate. / Master of Science

The quorum-sensing response of Vibrio fischeri involves a complex network of genes (encoding regulatory proteins as well as sRNAs), that govern host-association and production of bioluminescence. A key regulator of this system is LuxR, which is the transcriptional activator of the lux operon as well as several other genes in. LuxR also autoregulates its own transcription, which we have shown causes bistability and hysteresis in the quorum-sensing response. This behavior allows the system to maintain a stable and robust response in the face of environmental fluctuation or decreases in external autoinducer concentration caused by other sources. There are many factors that are known to regulate luxR expression, including the ArcA redox-responsive regulator, the cAMP-CRP secondary metabolism regulator, and components of the quorum-sensing pathway like LitR. Because of this, LuxR levels are critical in both the timing of quorum-sensing induction, as well as the maintenance of the response over time. This makes it a potential target for multiple levels of regulation in response to factors such as environmental and metabolic conditions, as well as other components of the quorum-sensing network. Another important global regulatory protein in V. fischeri (and most other species of Gram-negative proteobacteria) is the post-transcriptional regulator CsrA. CsrA controls processes involved in carbon storage and utilization, as well as the transition from exponential to stationary phase growth. We have demonstrated that CsrA is regulated by two sRNAs (CsrB1 and CsrB2) in V. fischeri. Because CsrA regulates changes in cell behavior and is an important metabolic regulator, there is a good possibility that it has some interactions with the quorum-sensing regulon, whose endproduct, bioluminescence, creates a large metabolic demand from the cell. In an effort to determine at which point in the quorum-sensing regulatory network CsrA regulation is important, epistasis experiments were designed using factorial design, which is a subset of statistical analysis of variance (ANOVA). This method was used to generate a high degree of confidence in the data, so that even minor interactions in the regulatory networks could be established. By altering the levels of CsrA expression in various mutant strains of V. fischeri, we have demonstrated that CsrA acts by an unknown mechanism to increase the transcription of luxR when the quorum-sensing regulator LitR is absent. Our results also demonstrated that CsrA mediates this effect through repression of ArcA activity, which is known to act directly on the luxR and luxI intergenic region as a repressor. This indicates that CsrA may bypass the upstream parts of the quorum-sensing regulatory cascade that lead to litR activation, so that LitR and LuxR may be regulated differently in response to certain conditions. This work has shown that the interactions between global regulons can coordinately control the amount of quorum-sensing induction by affecting the level of LuxR in the cell. The balance of these regulatory networks allows the cell to tightly regulate the quorum-sensing response. Thus, LuxR serves as a critical regulatory hub in the cell, at which multiple signals can be integrated in order to generate the appropriate cellular response. / Ph. D.

In 1993, Novak and Tyson published a comprehensive mathematical model of the regulation of M-phase promoting factor (MPF) activity in Xenopus laevis eggs and egg extracts. Although this model was in agreement with existing and subsequent experimental data, fundamental predictions that the cell cycle is driven by a hysteresis loop have never been validated experimentally. The model's predictions of bifurcations that create and destroy MPF activity, indicative of hysteresis, were tested in this study. <u>Prediction 1: The threshold concentration of cyclin B required to activate MPF is measurably higher than the threshold concentration required to inactivate MPF.</u> The difference in thresholds implies that the MPF control system is hysteretic and bistable. To measure these thresholds, extracts in interphase or M-phase were supplemented with varying concentrations of non-degradable human cyclin B1 protein. MPF activity was determined by the morphology of sperm nuclei and by assays of histone H1 kinase activity. Consistent with the model, the activation threshold was determined to be 40 nM, which is two-fold higher than the inactivation threshold, 20 nM. <u>Prediction 2: For cyclin levels marginally above the activation threshold concentration of cyclin B, there is a dramatic "slowing-down" in the rate of MPF activation.</u> Supra-threshold concentrations of nondegradable cyclin B1 were added to cycloheximide-treated CSF-released extracts, and samples taken at various time-points were analyzed for MPF activity. At 40 nM cyclin B1, just above the activation threshold, the lag time for MPF activation was 45 - 60 minutes; at 50 nM cyclin B1, the lag time was between 30 - 45 minutes; and at 60 nM or higher concentrations of cyclin B1, the lag time was 20 - 30 minutes, thus confirming the prediction of the Novak-Tyson model. <u>Prediction 3: DNA replication checkpoint increases the activation threshold concentration of cyclin B by increasing the hysteresis loop.</u> Cycloheximide-treated, CSF-released extracts containing 1200 sperm nuclei/&#956;l were treated with aphidicolin, then supplemented with varying concentrations of nondegradable cyclin B1. The activation threshold was 100 nM, 2.5 fold higher than in extracts lacking aphidicolin. <u>Conclusions:</u> These studies confirm three predictions of the Novak-Tyson model and indicate that hysteresis underlies cell cycle control in Xenopus egg extracts. These experiments validate use of mathematical models to study complex biological control systems such as the eukayotic cell cycle. / Master of Science