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- All Subjects: Cancer
Description
In complex consumer-resource type systems, where diverse individuals are interconnected and interdependent, one can often anticipate what has become known as the tragedy of the commons, i.e., a situation, when overly efficient consumers exhaust the common resource, causing collapse of the entire population. In this dissertation I use mathematical modeling to explore different variations on the consumer-resource type systems, identifying some possible transitional regimes that can precede the tragedy of the commons. I then reformulate it as a game of a multi-player prisoner's dilemma and study two possible approaches for preventing it, namely direct modification of players' payoffs through punishment/reward and modification of the environment in which the interactions occur. I also investigate the questions of whether the strategy of resource allocation for reproduction or competition would yield higher fitness in an evolving consumer-resource type system and demonstrate that the direction in which the system will evolve will depend not only on the state of the environment but largely on the initial composition of the population. I then apply the developed framework to modeling cancer as an evolving ecological system and draw conclusions about some alternative approaches to cancer treatment.
ContributorsKareva, Irina (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Collins, James (Committee member) / Nagy, John (Committee member) / Smith, Hal (Committee member) / Arizona State University (Publisher)
Created2012
Description
Combination therapy has shown to improve success for cancer treatment. Oncolytic virotherapy is cancer treatment that uses engineered viruses to specifically infect and kill cancer cells, without harming healthy cells. Immunotherapy boosts the body's natural defenses towards cancer. The combination of oncolytic virotherapy and immunotherapy is explored through deterministic systems of nonlinear differential equations, constructed to match experimental data for murine melanoma. Mathematical analysis was done in order to gain insight on the relationship between cancer, viruses and immune response. One extension of the model focuses on clinical needs, with the underlying goal to seek optimal treatment regimens; for both frequency and dose quantity. The models in this work were first used to estimate parameters from preclinical experimental data, to identify biologically realistic parameter values. Insight gained from the mathematical analysis in the first model, allowed for numerical analysis to explore optimal treatment regimens of combination oncolytic virotherapy and dendritic vaccinations. Permutations accounting for treatment scheduled were done to find regimens that reduce tumor size. Observations from the produced data lead to in silico exploration of immune-viral interactions. Results suggest under optimal settings, combination treatment works better than monotherapy of either type. The most optimal result suggests treatment over a longer period of time, with fractioned doses, while reducing the total dendritic vaccination quantity, and maintaining the maximum virotherapy used in the experimental work.
ContributorsSummer, Ilyssa Aimee (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Nagy, John (Thesis advisor) / Mubayi, Anuj (Committee member) / Kang, Yun (Committee member) / Arizona State University (Publisher)
Created2016
Description
The immune system plays a dual role during neoplastic progression. It can suppress tumor growth by eliminating cancer cells, and also promote neoplastic expansion by either selecting for tumor cells that are fitter to survive in an immunocompetent host or by establishing the right conditions within the tumor microenvironment. First, I present a model to study the dynamics of subclonal evolution of cancer. I model selection through time as an epistatic process. That is, the fitness change in a given cell is not simply additive, but depends on previous mutations. Simulation studies indicate that tumors are composed of myriads of small subclones at the time of diagnosis. Because some of these rare subclones harbor pre-existing treatment-resistant mutations, they present a major challenge to precision medicine. Second, I study the question of self and non-self discrimination by the immune system, which is fundamental in the field in cancer immunology. By performing a quantitative analysis of the biochemical properties of thousands of MHC class I peptides, I find that hydrophobicity of T cell receptors contact residues is a hallmark of immunogenic epitopes. Based on these findings, I further develop a computational model to predict immunogenic epitopes which facilitate the development of T cell vaccines against pathogen and tumor antigens. Lastly, I study the effect of early detection in the context of Ebola. I develope a simple mathematical model calibrated to the transmission dynamics of Ebola virus in West Africa. My findings suggest that a strategy that focuses on early diagnosis of high-risk individuals, caregivers, and health-care workers at the pre-symptomatic stage, when combined with public health measures to improve the speed and efficacy of isolation of infectious individuals, can lead to rapid reductions in Ebola transmission.
ContributorsChowell-Puente, Diego (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Anderson, Karen S (Thesis advisor) / Maley, Carlo C (Committee member) / Wilson Sayres, Melissa A (Committee member) / Blattman, Joseph N (Committee member) / Arizona State University (Publisher)
Created2016
Description
Through research, interviews, and analysis, our paper provides the local community with a resource that offers a comprehensive collection of insight into the Mirabella at ASU Life Plan Community and the projected impact it will have on the City of Tempe and Arizona State University.
ContributorsStephens, Corey Christopher (Co-author) / Dicke, George (Co-author) / Anand, Rohan (Co-author) / Sadusky, Brian (Thesis director) / Schiller, Christoph (Committee member) / Dean, W.P. Carey School of Business (Contributor) / Department of Finance (Contributor) / Sandra Day O'Connor College of Law (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Through research, interviews, and analysis, our paper provides the local community with a resource that offers a comprehensive collection of insight into the Mirabella at ASU Life Plan Community and the projected impact it will have on the City of Tempe and Arizona State University.
ContributorsAnand, Rohan (Co-author) / Dicke, George (Co-author) / Stephens, Corey (Co-author) / Sadusky, Brian (Thesis director) / Schiller, Christoph (Committee member) / Dean, W.P. Carey School of Business (Contributor) / Department of Finance (Contributor) / Department of Supply Chain Management (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Through research, interviews, and analysis, our paper provides the local community with a resource that offers a comprehensive collection of insight into the Mirabella at ASU Life Plan Community and the projected impact it will have on the City of Tempe and Arizona State University.
ContributorsDicke, George (Co-author) / Anand, Rohan (Co-author) / Stephens, Corey (Co-author) / Sadusky, Brian (Thesis director) / Schiller, Christoph (Committee member) / Dean, W.P. Carey School of Business (Contributor) / Department of Finance (Contributor) / Department of Information Systems (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
In order to deploy autonomous multi-robot teams for humanitarian demining in Colombia, two key problems need to be addressed. First, a robotic controller with limited power that can completely cover a dynamic search area is needed. Second, the Colombian National Army (COLAR) needs to increase its science, technology and innovation (STI) capacity to help develop, build and maintain such robots. Using Thangavelautham's (2012, 2017) Artificial Neural Tissue (ANT) control algorithm, a robotic controller for an autonomous multi-robot team was developed. Trained by a simple genetic algorithm, ANT is an artificial neural network (ANN) controller with a sparse, coarse coding network architecture and adaptive activation functions. Starting from the exterior of open, basic geometric grid areas, computer simulations of an ANT multi-robot team with limited time steps, no central controller and limited a priori information, covered some areas completely in linear time, and other areas near completely in quasi-linear time, comparable to the theoretical cover time bounds of grid-based, ant pheromone, area coverage algorithms. To mitigate catastrophic forgetting, a new learning method for ANT, Lifelong Adaptive Neuronal Learning (LANL) was developed, where neural network weight parameters for a specific coverage task were frozen, and only the activation function and output behavior parameters were re-trained for a new coverage task. The performance of the LANL controllers were comparable to training all parameters ab initio, for a new ANT controller for the new coverage task.
To increase COLAR's STI capacity, a proposal for a new STI officer corps, Project ÉLITE (Equipo de Líderes en Investigación y Tecnología del Ejército) was developed, where officers enroll in a research intensive, master of science program in applied mathematics or physics in Colombia, and conduct research in the US during their final year. ÉLITE is inspired by the Israel Defense Forces Talpiot program.
To increase COLAR's STI capacity, a proposal for a new STI officer corps, Project ÉLITE (Equipo de Líderes en Investigación y Tecnología del Ejército) was developed, where officers enroll in a research intensive, master of science program in applied mathematics or physics in Colombia, and conduct research in the US during their final year. ÉLITE is inspired by the Israel Defense Forces Talpiot program.
ContributorsKwon, Byong (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Thangavelautham, Jekanthan (Committee member) / Seshaiyer, Padmanabhan (Committee member) / Arizona State University (Publisher)
Created2019