A multimethod simulation paradigm for investigating complex cellular responses in biological systems of aging and disease
| dc.contributor.author | Hoffman, Timothy Edward, author | |
| dc.contributor.author | Hanneman, William H., advisor | |
| dc.contributor.author | Legare, Marie E., advisor | |
| dc.contributor.author | Wallis, Lyle E., committee member | |
| dc.contributor.author | Moreno, Julie A., committee member | |
| dc.date.accessioned | 2019-09-10T14:35:40Z | |
| dc.date.available | 2019-09-10T14:35:40Z | |
| dc.date.issued | 2019 | |
| dc.description.abstract | Classical studies in toxicology and disease research have relied on the use of high-dose experiments and often lacked quantitative and comprehensive components essential to understanding biological queries. These shortcomings in the research community have been the result of modern methodological limitations, however, more robust and expansive experimental and computational methods are emerging. In this dissertation, I present a novel multimethod computational simulation paradigm that adds value to new and existing studies of toxicological and pathological endeavors. First, I established the use of this approach for pharmacokinetic and pharmacodynamic applications, with published examples in regulatory exposure toxicology and contemporary dose-response nuances. Following establishing the success of this approach in toxicology, I then applied this methodology to the broader question of degenerative aging, as it has been arduous with conventional techniques to understand the various mechanisms that contribute to and protect against cellular aging. The foundational simulation created for general cellular aging was then expanded in the context of tauopathies and Alzheimer's disease to better quantify and understand the pathways involved in this age-dependent disorder. The final results presented here improve experimental translatability, robustness and descriptiveness in order to better understand age-related diseases. More broadly, this dissertation in totality attempts to minimize quantitative deficits in toxicological and pharmacological research. | |
| dc.format.medium | born digital | |
| dc.format.medium | doctoral dissertations | |
| dc.identifier | Hoffman_colostate_0053A_15527.pdf | |
| dc.identifier.uri | https://hdl.handle.net/10217/197305 | |
| dc.language | English | |
| dc.language.iso | eng | |
| dc.publisher | Colorado State University. Libraries | |
| dc.relation.ispartof | 2000-2019 | |
| dc.rights | Copyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright. | |
| dc.title | A multimethod simulation paradigm for investigating complex cellular responses in biological systems of aging and disease | |
| dc.type | Text | |
| dcterms.rights.dpla | This Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). | |
| thesis.degree.discipline | Environmental and Radiological Health Sciences | |
| thesis.degree.grantor | Colorado State University | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) |
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