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dc.contributor.advisorHanneman, William H.
dc.contributor.advisorLegare, Marie E.
dc.contributor.authorHoffman, Timothy Edward
dc.contributor.committeememberWallis, Lyle E.
dc.contributor.committeememberMoreno, Julie A.
dc.date.accessioned2019-09-10T14:35:40Z
dc.date.available2019-09-10T14:35:40Z
dc.date.issued2019
dc.description2019 Summer.
dc.descriptionIncludes bibliographical references.
dc.description.abstractClassical 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.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierHoffman_colostate_0053A_15527.pdf
dc.identifier.urihttps://hdl.handle.net/10217/197305
dc.languageEnglish
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019 - CSU Theses and Dissertations
dc.rightsCopyright of the original work is retained by the author.
dc.subjectaging
dc.subjectpharmacokinetics
dc.subjectsimulation modeling
dc.subjectmitochondria
dc.subjectagent-based modeling
dc.subjectreceptor dynamics
dc.titleMultimethod simulation paradigm for investigating complex cellular responses in biological systems of aging and disease, A
dc.typeText
dcterms.rights.dplaThe copyright and related rights status of this Item has not been evaluated (https://rightsstatements.org/vocab/CNE/1.0/). Please refer to the organization that has made the Item available for more information.
thesis.degree.disciplineEnvironmental and Radiological Health Sciences
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)


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