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- All Subjects: Applied Mathematics
- Creators: Castillo-Chavez, Carlos
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
This dissertation will look at large scale collaboration through the lens of online communities to answer questions about what makes a collaboration persist. Results address how collaborations attract contributions, behaviors that could give rise to patterns seen in the data, and the properties of collaborations that drive those behaviors.
It is understood that collaborations, online and otherwise, must retain users to remain productive. However, before users can be retained they must be recruited. In the first project, a few necessary properties of the ``attraction'' function are identified by constraining the dynamics of an ODE (Ordinary Differential Equation) model. Additionally, more than 100 communities of the Stack Exchange networks are parameterized and their distributions reported.
Collaborations do not exist in a vacuum, they compete with and share users with other collaborations. To address this, the second project focuses on an agent-based model (ABM) of a community of online collaborations using a mechanistic approach. The ABM is compared to data obtained from the Stack Exchange network and produces similar distributional patterns.
The third project is a thorough sensitivity analysis of the model created in the second project. A variance based sensitivity analysis is performed to evaluate the relative importance of 21 parameters of the model. Results indicate that population parameters impact many outcome metrics, though even those parameters that tend towards a low impact can be crucial for some outcomes.
It is understood that collaborations, online and otherwise, must retain users to remain productive. However, before users can be retained they must be recruited. In the first project, a few necessary properties of the ``attraction'' function are identified by constraining the dynamics of an ODE (Ordinary Differential Equation) model. Additionally, more than 100 communities of the Stack Exchange networks are parameterized and their distributions reported.
Collaborations do not exist in a vacuum, they compete with and share users with other collaborations. To address this, the second project focuses on an agent-based model (ABM) of a community of online collaborations using a mechanistic approach. The ABM is compared to data obtained from the Stack Exchange network and produces similar distributional patterns.
The third project is a thorough sensitivity analysis of the model created in the second project. A variance based sensitivity analysis is performed to evaluate the relative importance of 21 parameters of the model. Results indicate that population parameters impact many outcome metrics, though even those parameters that tend towards a low impact can be crucial for some outcomes.
ContributorsManning, Miles (Author) / Janssen, Marcus A (Thesis advisor) / Castillo-Chavez, Carlos (Thesis advisor) / Anderies, John M (Committee member) / Kang, Yun (Committee member) / Arizona State University (Publisher)
Created2017
Description
Head and neck squamous cell carcinoma (HNSCC), the sixth most common cancer
type worldwide, accounts for more than 630,000 new cases and 350,000 deaths
annually. Drug-resistance and tumor recurrence are the most challenging problems
in head and neck cancer treatment. It is hypothesized that a very small fraction
of stem-like cells within HNSCC tumor, called cancer stem cells (CSCs), is
responsible for tumor initiation, progression, resistance and recurrence. It has also
been shown that IL-6 secreted by head and neck tumor-associated endothelial cells
(ECs) enhances the survival, self-renewal and tumorigenic potential of head and
neck CSCs. In this study we will use a mathematical multi-scale model which operates
at the intracellular, molecular, and tissue level to investigate the impacts of
EC-secreted IL-6 signaling on the crosstalk between tumor cells and ECs during
tumor growth. This model will be calibrated by using the experimental in vivo
data.
Eventually the model will be modified to explore the responses of head and neck
cancer cells to combination therapy involving Tocilizumab (an anti-IL-6R antibody)
and Cisplatin (the most frequently used chemotherapy for head and neck
cancer). The model will be able to predict the final proportion of CSCs in response
to endothelial cell-secreted IL-6 and drug therapies. The model will be validated
by directly comparing the experimental treatment data and the model predictions.
This could potentially provide a condition under which we could control enlargement
of the head and neck CSC pool and tumor recurrence. It may also suggest
the best bounds for Cisplatin and/or Tocilizumab dose and frequency to be tested
in the clinical trial.
type worldwide, accounts for more than 630,000 new cases and 350,000 deaths
annually. Drug-resistance and tumor recurrence are the most challenging problems
in head and neck cancer treatment. It is hypothesized that a very small fraction
of stem-like cells within HNSCC tumor, called cancer stem cells (CSCs), is
responsible for tumor initiation, progression, resistance and recurrence. It has also
been shown that IL-6 secreted by head and neck tumor-associated endothelial cells
(ECs) enhances the survival, self-renewal and tumorigenic potential of head and
neck CSCs. In this study we will use a mathematical multi-scale model which operates
at the intracellular, molecular, and tissue level to investigate the impacts of
EC-secreted IL-6 signaling on the crosstalk between tumor cells and ECs during
tumor growth. This model will be calibrated by using the experimental in vivo
data.
Eventually the model will be modified to explore the responses of head and neck
cancer cells to combination therapy involving Tocilizumab (an anti-IL-6R antibody)
and Cisplatin (the most frequently used chemotherapy for head and neck
cancer). The model will be able to predict the final proportion of CSCs in response
to endothelial cell-secreted IL-6 and drug therapies. The model will be validated
by directly comparing the experimental treatment data and the model predictions.
This could potentially provide a condition under which we could control enlargement
of the head and neck CSC pool and tumor recurrence. It may also suggest
the best bounds for Cisplatin and/or Tocilizumab dose and frequency to be tested
in the clinical trial.
ContributorsNazari, Fereshteh (Author) / Jackson, Trachette L. (Thesis advisor, Committee member) / Castillo-Chavez, Carlos (Committee member) / Towers, Sherry (Committee member) / Kang, Yun (Committee member) / Arizona State University (Publisher)
Created2017
Description
This dissertation discusses the Cournot competition and competitions in the exploitation of common pool resources and its extension to the tragedy of the commons. I address these models by using potential games and inquire how these models reflect the real competitions for provisions of environmental resources. The Cournot models are dependent upon how many firms there are so that the resultant Cournot-Nash equilibrium is dependent upon the number of firms in oligopoly. But many studies do not take into account how the resultant Cournot-Nash equilibrium is sensitive to the change of the number of firms. Potential games can find out the outcome when the number of firms changes in addition to providing the "traditional" Cournot-Nash equilibrium when the number of firms is fixed. Hence, I use potential games to fill the gaps that exist in the studies of competitions in oligopoly and common pool resources and extend our knowledge in these topics. In specific, one of the rational conclusions from the Cournot model is that a firm's best policy is to split into separate firms. In real life, we usually witness the other way around; i.e., several firms attempt to merge and enjoy the monopoly profit by restricting the amount of output and raising the price. I aim to solve this conundrum by using potential games. I also clarify, within the Cournot competition model, how regulatory intervention in the management of environmental pollution externalities affects the equilibrium number of polluters. In addition, the tragedy of the commons is the term widely used to describe the overexploitation of open-access common-pool resources. Open-access encourages potential resource users to continue to enter the resource up to the point where rents are exhausted. The resulting level of resource use is higher than is socially optimal, and in extreme cases can lead to the collapse of the resource and the communities that may depend on it. In this paper I use the concept of potential games to evaluate the relation between the cost of resource use and the equilibrium number of resource users in open access regimes. I find that costs of access and costs of production are sufficient to determine the equilibrium number of resource users, and that there is in fact a continuum between Cournot competition and the tragedy of the commons. I note that the various common pool resource management regimes identified in the empirical literature are associated with particular cost structures, and hence that this may be the mechanism that determines the number of resource users accessing the resource.
ContributorsMamada, Robert H (Author) / Perrings, Charles (Thesis advisor) / Castillo-Chavez, Carlos (Thesis advisor) / Lampert, Adam (Committee member) / Arizona State University (Publisher)
Created2017
Description
A key factor in the success of social animals is their organization of work. Mathematical models have been instrumental in unraveling how simple, individual-based rules can generate collective patterns via self-organization. However, existing models offer limited insights into how these patterns are shaped by behavioral differences within groups, in part because they focus on analyzing specific rules rather than general mechanisms that can explain behavior at the individual-level. My work argues for a more principled approach that focuses on the question of how individuals make decisions in costly environments.
In Chapters 2 and 3, I demonstrate how this approach provides novel insights into factors that shape the flexibility and robustness of task organization in harvester ant colonies (Pogonomyrmex barbatus). My results show that the degree to which colonies can respond to work in fluctuating environments depends on how individuals weigh the costs of activity and update their behavior in response to social information. In Chapter 4, I introduce a mathematical framework to study the emergence of collective organization in heterogenous groups. My approach, which is based on the theory of multi-agent systems, focuses on myopic agents whose behavior emerges out of an independent valuation of alternative choices in a given work environment. The product of this dynamic is an equilibrium organization in which agents perform different tasks (or abstain from work) with an analytically defined set of threshold probabilities. The framework is minimally developed, but can be extended to include other factors known to affect task decisions including individual experience and social facilitation. This research contributes a novel approach to developing (and analyzing) models of task organization that can be applied in a broader range of contexts where animals cooperate.
In Chapters 2 and 3, I demonstrate how this approach provides novel insights into factors that shape the flexibility and robustness of task organization in harvester ant colonies (Pogonomyrmex barbatus). My results show that the degree to which colonies can respond to work in fluctuating environments depends on how individuals weigh the costs of activity and update their behavior in response to social information. In Chapter 4, I introduce a mathematical framework to study the emergence of collective organization in heterogenous groups. My approach, which is based on the theory of multi-agent systems, focuses on myopic agents whose behavior emerges out of an independent valuation of alternative choices in a given work environment. The product of this dynamic is an equilibrium organization in which agents perform different tasks (or abstain from work) with an analytically defined set of threshold probabilities. The framework is minimally developed, but can be extended to include other factors known to affect task decisions including individual experience and social facilitation. This research contributes a novel approach to developing (and analyzing) models of task organization that can be applied in a broader range of contexts where animals cooperate.
ContributorsUdiani, Oyita (Author) / Kang, Yun (Thesis advisor) / Fewell, Jennifer H (Thesis advisor) / Janssen, Marcus A (Committee member) / Castillo-Chavez, Carlos (Committee member) / Arizona State University (Publisher)
Created2016
Description
In the traditional setting of quantum mechanics, the Hamiltonian operator does not depend on time. While some Schrödinger equations with time-dependent Hamiltonians have been solved, explicitly solvable cases are typically scarce. This thesis is a collection of papers in which this first author along with Suslov, Suazo, and Lopez, has worked on solving a series of Schrödinger equations with a time-dependent quadratic Hamiltonian that has applications in problems of quantum electrodynamics, lasers, quantum devices such as quantum dots, and external varying fields. In particular the author discusses a new completely integrable case of the time-dependent Schrödinger equation in R^n with variable coefficients for a modified oscillator, which is dual with respect to the time inversion to a model of the quantum oscillator considered by Meiler, Cordero-Soto, and Suslov. A second pair of dual Hamiltonians is found in the momentum representation. Our examples show that in mathematical physics and quantum mechanics a change in the direction of time may require a total change of the system dynamics in order to return the system back to its original quantum state. The author also considers several models of the damped oscillators in nonrelativistic quantum mechanics in a framework of a general approach to the dynamics of the time-dependent Schrödinger equation with variable quadratic Hamiltonians. The Green functions are explicitly found in terms of elementary functions and the corresponding gauge transformations are discussed. The factorization technique is applied to the case of a shifted harmonic oscillator. The time-evolution of the expectation values of the energy related operators is determined for two models of the quantum damped oscillators under consideration. The classical equations of motion for the damped oscillations are derived for the corresponding expectation values of the position operator. Finally, the author constructs integrals of motion for several models of the quantum damped oscillators in a framework of a general approach to the time-dependent Schrödinger equation with variable quadratic Hamiltonians. An extension of the Lewis-Riesenfeld dynamical invariant is given. The time-evolution of the expectation values of the energy related positive operators is determined for the oscillators under consideration. A proof of uniqueness of the corresponding Cauchy initial value problem is discussed as an application.
ContributorsCordero-Soto, Ricardo J (Author) / Suslov, Sergei (Thesis advisor) / Castillo-Chavez, Carlos (Thesis advisor) / Engman, Martin (Committee member) / Herrera-Valdez, Marco (Committee member) / Arizona State University (Publisher)
Created2011
Description
Infectious diseases are a leading cause of death worldwide. With the development of drugs, vaccines and antibiotics, it was believed that for the first time in human history diseases would no longer be a major cause of mortality. Newly emerging diseases, re-emerging diseases and the emergence of microorganisms resistant to existing treatment have forced us to re-evaluate our optimistic perspective. In this study, a simple mathematical framework for super-infection is considered in order to explore the transmission dynamics of drug-resistance. Through its theoretical analysis, we identify the conditions necessary for the coexistence between sensitive strains and drug-resistant strains. Farther, in order to investigate the effectiveness of control measures, the model is extended so as to include vaccination and treatment. The impact that these preventive and control measures may have on its disease dynamics is evaluated. Theoretical results being confirmed via numerical simulations. Our theoretical results on two-strain drug-resistance models are applied in the context of Malaria, antimalarial drugs, and the administration of a possible partially effective vaccine. The objective is to develop a monitoring epidemiological framework that help evaluate the impact of antimalarial drugs and partially-effective vaccine in reducing the disease burden at the population level. Optimal control theory is applied in the context of this framework in order to assess the impact of time dependent cost-effective treatment efforts. It is shown that cost-effective combinations of treatment efforts depend on the population size, cost of implementing treatment controls, and the parameters of the model. We use these results to identify optimal control strategies for several scenarios.
ContributorsUrdapilleta, Alicia (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Wang, Xiaohong (Thesis advisor) / Wirkus, Stephen (Committee member) / Camacho, Erika (Committee member) / Arizona State University (Publisher)
Created2011
Description
The 2009-10 influenza and the 2014-15 Ebola pandemics brought once again urgency to an old question: What are the limits on prediction and what can be proposed that is useful in the face of an epidemic outbreak?
This thesis looks first at the impact that limited access to vaccine stockpiles may have on a single influenza outbreak. The purpose is to highlight the challenges faced by populations embedded in inadequate health systems and to identify and assess ways of ameliorating the impact of resource limitations on public health policy.
Age-specific per capita constraint rates play an important role on the dynamics of communicable diseases and, influenza is, of course, no exception. Yet the challenges associated with estimating age-specific contact rates have not been decisively met. And so, this thesis attempts to connect contact theory with age-specific contact data in the context of influenza outbreaks in practical ways. In mathematical epidemiology, proportionate mixing is used as the preferred theoretical mixing structure and so, the frame of discussion of this dissertation follows this specific theoretical framework. The questions that drive this dissertation, in the context of influenza dynamics, proportionate mixing, and control, are:
I. What is the role of age-aggregation on the dynamics of a single outbreak? Or simply speaking, does the number and length of the age-classes used to model a population make a significant difference on quantitative predictions?
II. What would the age-specific optimal influenza vaccination policies be? Or, what are the age-specific vaccination policies needed to control an outbreak in the presence of limited or unlimited vaccine stockpiles?
Intertwined with the above questions are issues of resilience and uncertainty including, whether or not data collected on mixing (by social scientists) can be used effectively to address both questions in the context of influenza and proportionate mixing. The objective is to provide answers to these questions by assessing the role of aggregation (number and length of age classes) and model robustness (does the aggregation scheme selected makes a difference on influenza dynamics and control) via comparisons between purely data-driven model and proportionate mixing models.
This thesis looks first at the impact that limited access to vaccine stockpiles may have on a single influenza outbreak. The purpose is to highlight the challenges faced by populations embedded in inadequate health systems and to identify and assess ways of ameliorating the impact of resource limitations on public health policy.
Age-specific per capita constraint rates play an important role on the dynamics of communicable diseases and, influenza is, of course, no exception. Yet the challenges associated with estimating age-specific contact rates have not been decisively met. And so, this thesis attempts to connect contact theory with age-specific contact data in the context of influenza outbreaks in practical ways. In mathematical epidemiology, proportionate mixing is used as the preferred theoretical mixing structure and so, the frame of discussion of this dissertation follows this specific theoretical framework. The questions that drive this dissertation, in the context of influenza dynamics, proportionate mixing, and control, are:
I. What is the role of age-aggregation on the dynamics of a single outbreak? Or simply speaking, does the number and length of the age-classes used to model a population make a significant difference on quantitative predictions?
II. What would the age-specific optimal influenza vaccination policies be? Or, what are the age-specific vaccination policies needed to control an outbreak in the presence of limited or unlimited vaccine stockpiles?
Intertwined with the above questions are issues of resilience and uncertainty including, whether or not data collected on mixing (by social scientists) can be used effectively to address both questions in the context of influenza and proportionate mixing. The objective is to provide answers to these questions by assessing the role of aggregation (number and length of age classes) and model robustness (does the aggregation scheme selected makes a difference on influenza dynamics and control) via comparisons between purely data-driven model and proportionate mixing models.
ContributorsMorales, Romarie (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Mubayi, Anuj (Thesis advisor) / Towers, Sherry (Committee member) / Arizona State University (Publisher)
Created2016
Description
This dissertation seeks to understand and study the process of attention harvesting and knowledge production on typical online Q&A communities. Goals of this study include quantifying the attention harvesting and online knowledge, damping the effect of competition for attention on knowledge production, and examining the diversity of user behaviors on question answering. Project 1 starts with a simplistic discrete time model on a scale-free network and provides the method to measure the attention harvested. Further, project 1 highlights the effect of distractions on harvesting productive attention and in the end concludes which factors are influential and sensitive to the attention harvesting. The main finding is the critical condition to optimize the attention harvesting on the network by reducing network connection. Project 2 extends the scope of the study to quantify the value and quality of knowledge, focusing on the question answering dynamics. This part of research models how attention was distributed under typical answering strategies on a virtual online Q&A community. The final result provides an approach to measure the efficiency of attention transferred into value production and observes the contribution of different scenarios under various computed metrics. Project 3 is an advanced study on the foundation of the virtual question answering community from project 2. With highlights of different user behavioral preferences, algorithm stochastically simulates individual decisions and behavior. Results from sensitivity analysis on different mixtures of user groups gives insight of nonlinear dynamics for the objectives of success. Simulation finding shows reputation rewarding mechanism on Stack Overflow shapes the crowd mixture of behavior to be successful. In addition, project proposed an attention allocation scenario of question answering to improve the success metrics when coupling with a particular selection strategy.
ContributorsYu, Fan, Ph.D (Author) / Janssen, Marcus A (Thesis advisor) / Kang, Yun (Committee member) / Castillo-Chavez, Carlos (Committee member) / Arizona State University (Publisher)
Created2019