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- All Subjects: Applied Mathematics
- Creators: Motsch, Sebastien
- Creators: Nagy, John
- Member of: Theses and Dissertations
- Resource Type: Text
Description
The phycologist, M. R. Droop, studied vitamin B12 limitation in the flagellate Monochrysis lutheri and concluded that its specific growth rate depended on the concentration of the vitamin within the cell; i.e. the cell quota of the vitamin B12. The Droop model provides a mathematical expression to link growth rate to the intracellular concentration of a limiting nutrient. Although the Droop model has been an important modeling tool in ecology, it has only recently been applied to study cancer biology. Cancer cells live in an ecological setting, interacting and competing with normal and other cancerous cells for nutrients and space, and evolving and adapting to their environment. Here, the Droop equation is used to model three cancers.
First, prostate cancer is modeled, where androgen is considered the limiting nutrient since most tumors depend on androgen for proliferation and survival. The model's accuracy for predicting the biomarker for patients on intermittent androgen deprivation therapy is tested by comparing the simulation results to clinical data as well as to an existing simpler model. The results suggest that a simpler model may be more beneficial for a predictive use, although further research is needed in this field prior to implementing mathematical models as a predictive method in a clinical setting.
Next, two chronic myeloid leukemia models are compared that consider Imatinib treatment, a drug that inhibits the constitutively active tyrosine kinase BCR-ABL. Both models describe the competition of leukemic and normal cells, however the first model also describes intracellular dynamics by considering BCR-ABL as the limiting nutrient. Using clinical data, the differences in estimated parameters between the models and the capacity for each model to predict drug resistance are analyzed.
Last, a simple model is presented that considers ovarian tumor growth and tumor induced angiogenesis, subject to on and off anti-angiogenesis treatment. In this environment, the cell quota represents the intracellular concentration of necessary nutrients provided through blood supply. Mathematical analysis of the model is presented and model simulation results are compared to pre-clinical data. This simple model is able to fit both on- and off-treatment data using the same biologically relevant parameters.
First, prostate cancer is modeled, where androgen is considered the limiting nutrient since most tumors depend on androgen for proliferation and survival. The model's accuracy for predicting the biomarker for patients on intermittent androgen deprivation therapy is tested by comparing the simulation results to clinical data as well as to an existing simpler model. The results suggest that a simpler model may be more beneficial for a predictive use, although further research is needed in this field prior to implementing mathematical models as a predictive method in a clinical setting.
Next, two chronic myeloid leukemia models are compared that consider Imatinib treatment, a drug that inhibits the constitutively active tyrosine kinase BCR-ABL. Both models describe the competition of leukemic and normal cells, however the first model also describes intracellular dynamics by considering BCR-ABL as the limiting nutrient. Using clinical data, the differences in estimated parameters between the models and the capacity for each model to predict drug resistance are analyzed.
Last, a simple model is presented that considers ovarian tumor growth and tumor induced angiogenesis, subject to on and off anti-angiogenesis treatment. In this environment, the cell quota represents the intracellular concentration of necessary nutrients provided through blood supply. Mathematical analysis of the model is presented and model simulation results are compared to pre-clinical data. This simple model is able to fit both on- and off-treatment data using the same biologically relevant parameters.
ContributorsEverett, Rebecca Anne (Author) / Kuang, Yang (Thesis advisor) / Nagy, John (Committee member) / Milner, Fabio (Committee member) / Crook, Sharon (Committee member) / Jackiewicz, Zdzislaw (Committee member) / Arizona State University (Publisher)
Created2015
Description
In 1968, phycologist M.R. Droop published his famous discovery on the functional relationship between growth rate and internal nutrient status of algae in chemostat culture. The simple notion that growth is directly dependent on intracellular nutrient concentration is useful for understanding the dynamics in many ecological systems. The cell quota in particular lends itself to ecological stoichiometry, which is a powerful framework for mathematical ecology. Three models are developed based on the cell quota principal in order to demonstrate its applications beyond chemostat culture.
First, a data-driven model is derived for neutral lipid synthesis in green microalgae with respect to nitrogen limitation. This model synthesizes several established frameworks in phycology and ecological stoichiometry. The model demonstrates how the cell quota is a useful abstraction for understanding the metabolic shift to neutral lipid production that is observed in certain oleaginous species.
Next a producer-grazer model is developed based on the cell quota model and nutrient recycling. The model incorporates a novel feedback loop to account for animal toxicity due to accumulation of nitrogen waste. The model exhibits rich, complex dynamics which leave several open mathematical questions.
Lastly, disease dynamics in vivo are in many ways analogous to those of an ecosystem, giving natural extensions of the cell quota concept to disease modeling. Prostate cancer can be modeled within this framework, with androgen the limiting nutrient and the prostate and cancer cells as competing species. Here the cell quota model provides a useful abstraction for the dependence of cellular proliferation and apoptosis on androgen and the androgen receptor. Androgen ablation therapy is often used for patients in biochemical recurrence or late-stage disease progression and is in general initially effective. However, for many patients the cancer eventually develops resistance months to years after treatment begins. Understanding how and predicting when hormone therapy facilitates evolution of resistant phenotypes has immediate implications for treatment. Cell quota models for prostate cancer can be useful tools for this purpose and motivate applications to other diseases.
First, a data-driven model is derived for neutral lipid synthesis in green microalgae with respect to nitrogen limitation. This model synthesizes several established frameworks in phycology and ecological stoichiometry. The model demonstrates how the cell quota is a useful abstraction for understanding the metabolic shift to neutral lipid production that is observed in certain oleaginous species.
Next a producer-grazer model is developed based on the cell quota model and nutrient recycling. The model incorporates a novel feedback loop to account for animal toxicity due to accumulation of nitrogen waste. The model exhibits rich, complex dynamics which leave several open mathematical questions.
Lastly, disease dynamics in vivo are in many ways analogous to those of an ecosystem, giving natural extensions of the cell quota concept to disease modeling. Prostate cancer can be modeled within this framework, with androgen the limiting nutrient and the prostate and cancer cells as competing species. Here the cell quota model provides a useful abstraction for the dependence of cellular proliferation and apoptosis on androgen and the androgen receptor. Androgen ablation therapy is often used for patients in biochemical recurrence or late-stage disease progression and is in general initially effective. However, for many patients the cancer eventually develops resistance months to years after treatment begins. Understanding how and predicting when hormone therapy facilitates evolution of resistant phenotypes has immediate implications for treatment. Cell quota models for prostate cancer can be useful tools for this purpose and motivate applications to other diseases.
ContributorsPacker, Aaron (Author) / Kuang, Yang (Thesis advisor) / Nagy, John (Committee member) / Smith, Hal (Committee member) / Kostelich, Eric (Committee member) / Kang, Yun (Committee member) / Arizona State University (Publisher)
Created2014
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
Swarms of animals, fish, birds, locusts etc. are a common occurrence but their coherence and method of organization poses a major question for mathematics and biology.The Vicsek and the Attraction-Repulsion are two models that have been proposed to explain the emergence of collective motion. A major issue for the Vicsek Model is that its particles are not attracted to each other, leaving the swarm with alignment in velocity but without spatial coherence. Restricting the particles to a bounded domain generates global spatial coherence of swarms while maintaining velocity alignment. While individual particles are specularly reflected at the boundary, the swarm as a whole is not. As a result, new dynamical swarming solutions are found.
The Attraction-Repulsion Model set with a long-range attraction and short-range repulsion interaction potential typically stabilizes to a well-studied flock steady state solution. The particles for a flock remain spatially coherent but have no spatial bound and explore all space. A bounded domain with specularly reflecting walls traps the particles within a specific region. A fundamental refraction law for a swarm impacting on a planar boundary is derived. The swarm reflection varies from specular for a swarm dominated by
kinetic energy to inelastic for a swarm dominated by potential energy. Inelastic collisions lead to alignment with the wall and to damped pulsating oscillations of the swarm. The fundamental refraction law provides a one-dimensional iterative map that allows for a prediction and analysis of the trajectory of the center of mass of a flock in a channel and a square domain.
The extension of the wall collisions to a scattering experiment is conducted by setting two identical flocks to collide. The two particle dynamics is studied analytically and shows a transition from scattering: diverging flocks to bound states in the form of oscillations or parallel motions. Numerical studies of collisions of flocks show the same transition where the bound states become either a single translating flock or a rotating (mill).
The Attraction-Repulsion Model set with a long-range attraction and short-range repulsion interaction potential typically stabilizes to a well-studied flock steady state solution. The particles for a flock remain spatially coherent but have no spatial bound and explore all space. A bounded domain with specularly reflecting walls traps the particles within a specific region. A fundamental refraction law for a swarm impacting on a planar boundary is derived. The swarm reflection varies from specular for a swarm dominated by
kinetic energy to inelastic for a swarm dominated by potential energy. Inelastic collisions lead to alignment with the wall and to damped pulsating oscillations of the swarm. The fundamental refraction law provides a one-dimensional iterative map that allows for a prediction and analysis of the trajectory of the center of mass of a flock in a channel and a square domain.
The extension of the wall collisions to a scattering experiment is conducted by setting two identical flocks to collide. The two particle dynamics is studied analytically and shows a transition from scattering: diverging flocks to bound states in the form of oscillations or parallel motions. Numerical studies of collisions of flocks show the same transition where the bound states become either a single translating flock or a rotating (mill).
ContributorsThatcher, Andrea (Author) / Armbruster, Hans (Thesis advisor) / Motsch, Sebastien (Committee member) / Ringhofer, Christian (Committee member) / Platte, Rodrigo (Committee member) / Gardner, Carl (Committee member) / Arizona State University (Publisher)
Created2015
Description
Predicting resistant prostate cancer is critical for lowering medical costs and improving the quality of life of advanced prostate cancer patients. I formulate, compare, and analyze two mathematical models that aim to forecast future levels of prostate-specific antigen (PSA). I accomplish these tasks by employing clinical data of locally advanced prostate cancer patients undergoing androgen deprivation therapy (ADT). I demonstrate that the inverse problem of parameter estimation might be too complicated and simply relying on data fitting can give incorrect conclusions, since there is a large error in parameter values estimated and parameters might be unidentifiable. I provide confidence intervals to give estimate forecasts using data assimilation via an ensemble Kalman Filter. Using the ensemble Kalman Filter, I perform dual estimation of parameters and state variables to test the prediction accuracy of the models. Finally, I present a novel model with time delay and a delay-dependent parameter. I provide a geometric stability result to study the behavior of this model and show that the inclusion of time delay may improve the accuracy of predictions. Also, I demonstrate with clinical data that the inclusion of the delay-dependent parameter facilitates the identification and estimation of parameters.
ContributorsBaez, Javier (Author) / Kuang, Yang (Thesis advisor) / Kostelich, Eric (Committee member) / Crook, Sharon (Committee member) / Gardner, Carl (Committee member) / Nagy, John (Committee member) / Arizona State University (Publisher)
Created2017
Description
Need-based transfers (NBTs) are a form of risk-pooling in which binary welfare exchanges
occur to preserve the viable participation of individuals in an economy, e.g. reciprocal gifting
of cattle among East African herders or food sharing among vampire bats. With the
broad goal of better understanding the mathematics of such binary welfare and risk pooling,
agent-based simulations are conducted to explore socially optimal transfer policies
and sharing network structures, kinetic exchange models that utilize tools from the kinetic
theory of gas dynamics are utilized to characterize the wealth distribution of an NBT economy,
and a variant of repeated prisoner’s dilemma is analyzed to determine whether and
why individuals would participate in such a system of reciprocal altruism.
From agent-based simulation and kinetic exchange models, it is found that regressive
NBT wealth redistribution acts as a cutting stock optimization heuristic that most efficiently
matches deficits to surpluses to improve short-term survival; however, progressive
redistribution leads to a wealth distribution that is more stable in volatile environments and
therefore is optimal for long-term survival. Homogeneous sharing networks with low variance
in degree are found to be ideal for maintaining community viability as the burden and
benefit of NBTs is equally shared. Also, phrasing NBTs as a survivor’s dilemma reveals
parameter regions where the repeated game becomes equivalent to a stag hunt or harmony
game, and thus where cooperation is evolutionarily stable.
occur to preserve the viable participation of individuals in an economy, e.g. reciprocal gifting
of cattle among East African herders or food sharing among vampire bats. With the
broad goal of better understanding the mathematics of such binary welfare and risk pooling,
agent-based simulations are conducted to explore socially optimal transfer policies
and sharing network structures, kinetic exchange models that utilize tools from the kinetic
theory of gas dynamics are utilized to characterize the wealth distribution of an NBT economy,
and a variant of repeated prisoner’s dilemma is analyzed to determine whether and
why individuals would participate in such a system of reciprocal altruism.
From agent-based simulation and kinetic exchange models, it is found that regressive
NBT wealth redistribution acts as a cutting stock optimization heuristic that most efficiently
matches deficits to surpluses to improve short-term survival; however, progressive
redistribution leads to a wealth distribution that is more stable in volatile environments and
therefore is optimal for long-term survival. Homogeneous sharing networks with low variance
in degree are found to be ideal for maintaining community viability as the burden and
benefit of NBTs is equally shared. Also, phrasing NBTs as a survivor’s dilemma reveals
parameter regions where the repeated game becomes equivalent to a stag hunt or harmony
game, and thus where cooperation is evolutionarily stable.
ContributorsKayser, Kirk (Author) / Armbruster, Dieter (Thesis advisor) / Lampert, Adam (Committee member) / Ringhofer, Christian (Committee member) / Motsch, Sebastien (Committee member) / Gardner, Carl (Committee member) / Arizona State University (Publisher)
Created2018
Description
The role of climate change, as measured in terms of changes in the climatology of geophysical variables (such as temperature and rainfall), on the global distribution and burden of vector-borne diseases (VBDs) remains a subject of considerable debate. This dissertation attempts to contribute to this debate via the use of mathematical (compartmental) modeling and statistical data analysis. In particular, the objective is to find suitable values and/or ranges of the climate variables considered (typically temperature and rainfall) for maximum vector abundance and consequently, maximum transmission intensity of the disease(s) they cause.
Motivated by the fact that understanding the dynamics of disease vector is crucial to understanding the transmission and control of the VBDs they cause, a novel weather-driven deterministic model for the population biology of the mosquito is formulated and rigorously analyzed. Numerical simulations, using relevant weather and entomological data for Anopheles mosquito (the vector for malaria), show that maximum mosquito abundance occurs when temperature and rainfall values lie in the range [20-25]C and [105-115] mm, respectively.
The Anopheles mosquito ecology model is extended to incorporate human dynamics. The resulting weather-driven malaria transmission model, which includes many of the key aspects of malaria (such as disease transmission by asymptomatically-infectious humans, and enhanced malaria immunity due to repeated exposure), was rigorously analyzed. The model which also incorporates the effect of diurnal temperature range (DTR) on malaria transmission dynamics shows that increasing DTR shifts the peak temperature value for malaria transmission from 29C (when DTR is 0C) to about 25C (when DTR is 15C).
Finally, the malaria model is adapted and used to study the transmission dynamics of chikungunya, dengue and Zika, three diseases co-circulating in the Americas caused by the same vector (Aedes aegypti). The resulting model, which is fitted using data from Mexico, is used to assess a few hypotheses (such as those associated with the possible impact the newly-released dengue vaccine will have on Zika) and the impact of variability in climate variables on the dynamics of the three diseases. Suitable temperature and rainfall ranges for the maximum transmission intensity of the three diseases are obtained.
Motivated by the fact that understanding the dynamics of disease vector is crucial to understanding the transmission and control of the VBDs they cause, a novel weather-driven deterministic model for the population biology of the mosquito is formulated and rigorously analyzed. Numerical simulations, using relevant weather and entomological data for Anopheles mosquito (the vector for malaria), show that maximum mosquito abundance occurs when temperature and rainfall values lie in the range [20-25]C and [105-115] mm, respectively.
The Anopheles mosquito ecology model is extended to incorporate human dynamics. The resulting weather-driven malaria transmission model, which includes many of the key aspects of malaria (such as disease transmission by asymptomatically-infectious humans, and enhanced malaria immunity due to repeated exposure), was rigorously analyzed. The model which also incorporates the effect of diurnal temperature range (DTR) on malaria transmission dynamics shows that increasing DTR shifts the peak temperature value for malaria transmission from 29C (when DTR is 0C) to about 25C (when DTR is 15C).
Finally, the malaria model is adapted and used to study the transmission dynamics of chikungunya, dengue and Zika, three diseases co-circulating in the Americas caused by the same vector (Aedes aegypti). The resulting model, which is fitted using data from Mexico, is used to assess a few hypotheses (such as those associated with the possible impact the newly-released dengue vaccine will have on Zika) and the impact of variability in climate variables on the dynamics of the three diseases. Suitable temperature and rainfall ranges for the maximum transmission intensity of the three diseases are obtained.
ContributorsOkuneye, Kamaldeen O (Author) / Gumel, Abba B (Thesis advisor) / Kuang, Yang (Committee member) / Smith, Hal (Committee member) / Thieme, Horst (Committee member) / Nagy, John (Committee member) / Arizona State University (Publisher)
Created2018
Description
This dissertation examines six different models in the field of econophysics using interacting particle systems as the basis of exploration. In each model examined, the underlying structure is a graph G = (V , E ), where each x ∈ V represents an individual who is characterized by the number of coins in her possession at time t. At each time step t, an edge (x, y) ∈ E is chosen at random, resulting in an exchange of coins between individuals x and y according to the rules of the model. Random variables ξt, and ξt(x) keep track of the current configuration and number of coins individual x has at time t respectively. Of particular interest is the distribution of coins in the long run. Considered first are the uniform reshuffling model, immediate exchange model and model with saving propensity. For each of these models, the number of coins an individual can have is nonnegative and the total number of coins in the system is conserved for all time. It is shown here that the distribution of coins converges to the exponential distribution, gamma distribution and a pseudo gamma distribution respectively. The next two models introduce debt, however, the total number of coins again remains fixed. It is shown here that when there is an individual debt limit, the number of coins per individual converges to a shifted exponential distribution. Alternatively, when a collective debt limit is imposed on the whole population, a heuristic argument is given supporting the conjecture that the distribution of coins converges to an asymmetric Laplace distribution. The final model considered focuses on the effect of cooperation on a population. Unlike the previous models discussed here, the total number of coins in the system at any given time is not bounded and the process evolves in continuous time rather than in discrete time. For this model, death of an individual will occur if they run out of coins. It is shown here that the survival probability for the population is impacted by the level of cooperation along with how productive the population is as whole.
ContributorsReed, Stephanie Jo (Author) / Lanchier, Nicolas (Thesis advisor) / Smith, Hal (Committee member) / Gumel, Abba (Committee member) / Motsch, Sebastien (Committee member) / Camacho, Erika (Committee member) / Arizona State University (Publisher)
Created2019
Description
I investigate two models interacting agent systems: the first is motivated by the flocking and swarming behaviors in biological systems, while the second models opinion formation in social networks. In each setting, I define natural notions of convergence (to a ``flock" and to a ``consensus'', respectively), and study the convergence properties of each in the limit as $t \rightarrow \infty$. Specifically, I provide sufficient conditions for the convergence of both of the models, and conduct numerical experiments to study the resulting solutions.
ContributorsTheisen, Ryan (Author) / Motsch, Sebastien (Thesis advisor) / Lanchier, Nicholas (Committee member) / Kostelich, Eric (Committee member) / Arizona State University (Publisher)
Created2018
Description
The retina is the lining in the back of the eye responsible for vision. When light photons hits the retina, the photoreceptors within the retina respond by sending impulses to the optic nerve, which connects to the brain. If there is injury to the eye or heredity retinal problems, this part can become detached. Detachment leads to loss of nutrients, such as oxygen and glucose, to the cells in the eye and causes cell death. Sometimes the retina is able to be surgically reattached. If the photoreceptor cells have not died and the reattachment is successful, then these cells are able to regenerate their outer segments (OS) which are essential for their functionality and vitality. In this work we will explore how the regrowth of the photoreceptor cells in a healthy eye after retinal detachment can lead to a deeper understanding of how eye cells take up nutrients and regenerate. This work uses a mathematical model for a healthy eye in conjunction with data for photoreceptors' regrowth and decay. The parameters for the healthy eye model are estimated from the data and the ranges of these parameter values are centered +/- 10\% away from these values are used for sensitivity analysis. Using parameter estimation and sensitivity analysis we can better understand how certain processes represented by these parameters change within the model as a result of retinal detachment. Having a deeper understanding for any sort of photoreceptor death and growth can be used by the greater scientific community to help with these currently irreversible conditions that lead to blindness, such as retinal detachment. The analysis in this work shows that maximizing the carrying capacity of the trophic pool and the rate of RDCVF, as well as minimizing nutrient withdrawal of the rods and the cones from the trophic pool results in both the most regrowth and least cell death in retinal detachment.
ContributorsGoldman, Miriam Ayla (Author) / Camacho, Erikia (Thesis director) / Wirkus, Stephen (Committee member) / School of Mathematical and Natural Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2017-05