In this work we have developed three ordinary differential equation models of biological systems: body mass change in response to exercise, immune system response to a general inflammatory stimulus, and the immune system response in atherosclerosis. The purpose of developing such computational tools is to test hypotheses about the underlying biological processes that drive system outcomes as well as possible real medical interventions. Therefore, we focus our analysis on understanding key interactions between model parameters and outcomes to deepen our understanding of these complex processes as a means to developing effective treatments in obesity, sarcopenia, and inflammatory diseases.
We develop a model of the dynamics of muscle hypertrophy in response to resistance exercise and have shown that the parameters controlling response vary between male and female group means in an elderly population. We further explore this individual variability by fitting to data from a clinical obesity study. We then apply logistic regression and classification tree methods to the analysis of between- and within-group differences in underlying physiology that lead to different long-term body composition outcomes following a diet or exercise program. Finally, we explore dieting strategies using optimal control methods.
Next, we extend an existing model of inflammation to include different macrophage phenotypes. Complications with this phenotype switch can result in the accumulation of too many of either type and lead to chronic wounds or disease. With this model we are able to reproduce the expected timing of sequential influx of immune cells and mediators in a general inflammatory setting. We then calibrate this base model for the sequential response of immune cells with peritoneal cavity data from mice. Next, we develop a model for plaque formation in atherosclerosis by adapting the current inflammation model to capture the progression of macrophages to inflammatory foam cells in response to cholesterol consumption. The purpose of this work is ultimately to explore points of intervention that can lead to homeostasis.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-7003 |
| Date | 01 January 2019 |
| Creators | Torres, Marcella |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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