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A general continuum model for simulating the flow of ions in the salt baths that surround and fill excitable neurons is developed and presented. The ion densities and electric potential are computed using the drift-diffusion equations. In addition, a detailed model is given for handling the electrical dynamics on interior

A general continuum model for simulating the flow of ions in the salt baths that surround and fill excitable neurons is developed and presented. The ion densities and electric potential are computed using the drift-diffusion equations. In addition, a detailed model is given for handling the electrical dynamics on interior membrane boundaries, including a model for ion channels in the membranes that facilitate the transfer of ions in and out of cells. The model is applied to the triad synapse found in the outer plexiform layer of the retina in most species. Experimental evidence suggests the existence of a negative feedback pathway between horizontal cells and cone photoreceptors that modulates the flow of calcium ions into the synaptic terminals of cones. However, the underlying mechanism for this feedback is controversial and there are currently three competing hypotheses: the ephaptic hypothesis, the pH hypothesis and the GABA hypothesis. The goal of this work is to test some features of the ephaptic hypothesis using detailed simulations that employ rigorous numerical methods. The model is first applied in a simple rectangular geometry to demonstrate the effects of feedback for different extracellular gap widths. The model is then applied to a more complex and realistic geometry to demonstrate the existence of strictly electrical feedback, as predicted by the ephaptic hypothesis. Lastly, the effects of electrical feedback in regards to the behavior of the bipolar cell membrane potential is explored. Figures for the ion densities and electric potential are presented to verify key features of the model. The computed steady state IV curves for several cases are presented, which can be compared to experimental data. The results provide convincing evidence in favor of the ephaptic hypothesis since the existence of feedback that is strictly electrical in nature is shown, without any dependence on pH effects or chemical transmitters.
ContributorsJones, Jeremiah (Author) / Gardner, Carl (Committee member) / Baer, Steven (Committee member) / Crook, Sharon (Committee member) / Kostelich, Eric (Committee member) / Ringhofer, Christian (Committee member) / Arizona State University (Publisher)
Created2013
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Description
This thesis considers the application of basis pursuit to several problems in system identification. After reviewing some key results in the theory of basis pursuit and compressed sensing, numerical experiments are presented that explore the application of basis pursuit to the black-box identification of linear time-invariant (LTI) systems with both

This thesis considers the application of basis pursuit to several problems in system identification. After reviewing some key results in the theory of basis pursuit and compressed sensing, numerical experiments are presented that explore the application of basis pursuit to the black-box identification of linear time-invariant (LTI) systems with both finite (FIR) and infinite (IIR) impulse responses, temporal systems modeled by ordinary differential equations (ODE), and spatio-temporal systems modeled by partial differential equations (PDE). For LTI systems, the experimental results illustrate existing theory for identification of LTI FIR systems. It is seen that basis pursuit does not identify sparse LTI IIR systems, but it does identify alternate systems with nearly identical magnitude response characteristics when there are small numbers of non-zero coefficients. For ODE systems, the experimental results are consistent with earlier research for differential equations that are polynomials in the system variables, illustrating feasibility of the approach for small numbers of non-zero terms. For PDE systems, it is demonstrated that basis pursuit can be applied to system identification, along with a comparison in performance with another existing method. In all cases the impact of measurement noise on identification performance is considered, and it is empirically observed that high signal-to-noise ratio is required for successful application of basis pursuit to system identification problems.
ContributorsThompson, Robert C. (Author) / Platte, Rodrigo (Thesis advisor) / Gelb, Anne (Committee member) / Cochran, Douglas (Committee member) / Arizona State University (Publisher)
Created2012
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Description
In vertebrate outer retina, changes in the membrane potential of horizontal cells affect the calcium influx and glutamate release of cone photoreceptors via a negative feedback. This feedback has a number of important physiological consequences. One is called background-induced flicker enhancement (BIFE) in which the onset of dim background enhances

In vertebrate outer retina, changes in the membrane potential of horizontal cells affect the calcium influx and glutamate release of cone photoreceptors via a negative feedback. This feedback has a number of important physiological consequences. One is called background-induced flicker enhancement (BIFE) in which the onset of dim background enhances the center flicker response of horizontal cells. The underlying mechanism for the feedback is still unclear but competing hypotheses have been proposed. One is the GABA hypothesis, which states that the feedback is mediated by gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter released from horizontal cells. Another is the ephaptic hypothesis, which contends that the feedback is non-GABAergic and is achieved through the modulation of electrical potential in the intersynaptic cleft between cones and horizontal cells. In this study, a continuum spine model of the cone-horizontal cell synaptic circuitry is formulated. This model, a partial differential equation system, incorporates both the GABA and ephaptic feedback mechanisms. Simulation results, in comparison with experiments, indicate that the ephaptic mechanism is necessary in order for the model to capture the major spatial and temporal dynamics of the BIFE effect. In addition, simulations indicate that the GABA mechanism may play some minor modulation role.
ContributorsChang, Shaojie (Author) / Baer, Steven M. (Thesis advisor) / Gardner, Carl L (Thesis advisor) / Crook, Sharon M (Committee member) / Kuang, Yang (Committee member) / Ringhofer, Christian (Committee member) / Arizona State University (Publisher)
Created2012
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Description
This dissertation involves three problems that are all related by the use of the singular value decomposition (SVD) or generalized singular value decomposition (GSVD). The specific problems are (i) derivation of a generalized singular value expansion (GSVE), (ii) analysis of the properties of the chi-squared method for regularization parameter selection

This dissertation involves three problems that are all related by the use of the singular value decomposition (SVD) or generalized singular value decomposition (GSVD). The specific problems are (i) derivation of a generalized singular value expansion (GSVE), (ii) analysis of the properties of the chi-squared method for regularization parameter selection in the case of nonnormal data and (iii) formulation of a partial canonical correlation concept for continuous time stochastic processes. The finite dimensional SVD has an infinite dimensional generalization to compact operators. However, the form of the finite dimensional GSVD developed in, e.g., Van Loan does not extend directly to infinite dimensions as a result of a key step in the proof that is specific to the matrix case. Thus, the first problem of interest is to find an infinite dimensional version of the GSVD. One such GSVE for compact operators on separable Hilbert spaces is developed. The second problem concerns regularization parameter estimation. The chi-squared method for nonnormal data is considered. A form of the optimized regularization criterion that pertains to measured data or signals with nonnormal noise is derived. Large sample theory for phi-mixing processes is used to derive a central limit theorem for the chi-squared criterion that holds under certain conditions. Departures from normality are seen to manifest in the need for a possibly different scale factor in normalization rather than what would be used under the assumption of normality. The consequences of our large sample work are illustrated by empirical experiments. For the third problem, a new approach is examined for studying the relationships between a collection of functional random variables. The idea is based on the work of Sunder that provides mappings to connect the elements of algebraic and orthogonal direct sums of subspaces in a Hilbert space. When combined with a key isometry associated with a particular Hilbert space indexed stochastic process, this leads to a useful formulation for situations that involve the study of several second order processes. In particular, using our approach with two processes provides an independent derivation of the functional canonical correlation analysis (CCA) results of Eubank and Hsing. For more than two processes, a rigorous derivation of the functional partial canonical correlation analysis (PCCA) concept that applies to both finite and infinite dimensional settings is obtained.
ContributorsHuang, Qing (Author) / Eubank, Randall (Thesis advisor) / Renaut, Rosemary (Thesis advisor) / Cochran, Douglas (Committee member) / Gelb, Anne (Committee member) / Young, Dennis (Committee member) / Arizona State University (Publisher)
Created2012
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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

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
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Description
Recent experimental and mathematical work has shown the interdependence of the rod and cone photoreceptors with the retinal pigment epithelium in maintaining sight. Accelerated intake of glucose into the cones via the theoredoxin-like rod-derived cone viability factor (RdCVF) is needed as aerobic glycolysis is the primary source of energy

Recent experimental and mathematical work has shown the interdependence of the rod and cone photoreceptors with the retinal pigment epithelium in maintaining sight. Accelerated intake of glucose into the cones via the theoredoxin-like rod-derived cone viability factor (RdCVF) is needed as aerobic glycolysis is the primary source of energy production. Reactive oxidative species (ROS) result from the rod and cone metabolism and recent experimental work has shown that the long form of RdCVF (RdCVFL) helps mitigate the negative effects of ROS. In this work I investigate the role of RdCVFL in maintaining the health of the photoreceptors. The results of this mathematical model show the necessity of RdCVFL and also demonstrate additional stable modes that are present in this system. The sensitivity analysis shows the importance of glucose uptake, nutrient levels, and ROS mitigation in maintaining rod and cone health in light-damaged mouse models. Together, these suggest areas on which to focus treatment in order to prolong the photoreceptors, especially in situations where ROS is a contributing factor to their death such as retinitis pigmentosa (RP). A potential treatment with RdCVFL and its effects has never been studied in mathematical models. In this work, I examine an optimal control with the treatment of RdCVFL and mathematically illustrate the potential that this treatment might have for treating degenerative retinal diseases such as RP. Further, I examine optimal controls with the treatment of both RdCVF and RdCVFL in order to mathematically understand the potential that a dual treatment might have for treating degenerative retinal diseases such as RP. The RdCVFL control terms are nonlinear for biological accuracy but this results in the standard general theorems for existence of optimal controls failing to apply. I then linearize these models to have proof of existence of an optimal control. Both nonlinear and linearized control results are compared and reveal similarly substantial savings rates for rods and cones.
ContributorsWifvat, Kathryn (Author) / Camacho, Erika (Thesis advisor) / Wirkus, Stephen (Thesis advisor) / Gardner, Carl (Committee member) / Fricks, John (Committee member) / Kawski, Matthias (Committee member) / Arizona State University (Publisher)
Created2022
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Description
\begin{abstract}The human immunodeficiency virus (HIV) pandemic, which causes the syndrome of opportunistic infections that characterize the late stage HIV disease, known as the acquired immunodeficiency syndrome (AIDS), remains a major public health challenge to many parts of the world. This dissertation contributes in providing deeper qualitative insights into the transmission

\begin{abstract}The human immunodeficiency virus (HIV) pandemic, which causes the syndrome of opportunistic infections that characterize the late stage HIV disease, known as the acquired immunodeficiency syndrome (AIDS), remains a major public health challenge to many parts of the world. This dissertation contributes in providing deeper qualitative insights into the transmission dynamics and control of the HIV/AIDS disease in Men who have Sex with Men (MSM) community. A new mathematical model (which is relatively basic), which incorporates some of the pertinent aspects of HIV epidemiology and immunology and fitted using the yearly new case data of the MSM population from the State of Arizona, was designed and used to assess the population-level impact of awareness of HIV infection status and condom-based intervention, on the transmission dynamics and control of HIV/AIDS in an MSM community. Conditions for the existence and asymptotic stability of the various equilibria ofthe model were derived. The numerical simulations showed that the prospects for the effective control and/or elimination of HIV/AIDS in the MSM community in the United States are very promising using a condom-based intervention, provided the condom efficacy is high and the compliance is moderate enough. The model was extended in Chapter 3 to account for the effect of risk-structure, staged-progression property of HIV disease, and the use of pre-exposure prophylaxis (PrEP) on the spread and control of the disease. The model was shown to undergo a PrEP-induced \textit{backward bifurcation} when the associated control reproduction number is less than one. It was shown that when the compliance in PrEP usage is $50%(80%)$ then about $19.1%(34.2%)$ of the yearly new HIV/AIDS cases recorded at the peak will have been prevented, in comparison to the worst-case scenario where PrEP-based intervention is not implemented in the MSM community. It was also shown that the HIV pandemic elimination is possible from the MSM community even for the scenario when the effective contact rate is increased by 5-fold from its baseline value, if low-risk individuals take at least 15 years before they change their risky behavior and transition to the high-risk group (regardless of the value of the transition rate from high-risk to low-risk susceptible population).
ContributorsTollett, Queen Wiggs (Author) / Gumel, Abba (Thesis advisor) / Crook, Sharon (Committee member) / Fricks, John (Committee member) / Gardner, Carl (Committee member) / Nagy, John (Committee member) / Arizona State University (Publisher)
Created2023
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A description of numerical and analytical work pertaining to models that describe the growth and progression of glioblastoma multiforme (GBM), an aggressive form of primary brain cancer. Two reaction-diffusion models are used: the Fisher-Kolmogorov-Petrovsky-Piskunov equation and a 2-population model that divides the tumor into actively proliferating and quiescent (or necrotic)

A description of numerical and analytical work pertaining to models that describe the growth and progression of glioblastoma multiforme (GBM), an aggressive form of primary brain cancer. Two reaction-diffusion models are used: the Fisher-Kolmogorov-Petrovsky-Piskunov equation and a 2-population model that divides the tumor into actively proliferating and quiescent (or necrotic) cells. The numerical portion of this work (chapter 2) focuses on simulating GBM expansion in patients undergoing treatment for recurrence of tumor following initial surgery. The models are simulated on 3-dimensional brain geometries derived from magnetic resonance imaging (MRI) scans provided by the Barrow Neurological Institute. The study consists of 17 clinical time intervals across 10 patients that have been followed in detail, each of whom shows significant progression of tumor over a period of 1 to 3 months on sequential follow up scans. A Taguchi sampling design is implemented to estimate the variability of the predicted tumors to using 144 different choices of model parameters. In 9 cases, model parameters can be identified such that the simulated tumor contains at least 40 percent of the volume of the observed tumor. In the analytical portion of the paper (chapters 3 and 4), a positively invariant region for our 2-population model is identified. Then, a rigorous derivation of the critical patch size associated with the model is performed. The critical patch (KISS) size is the minimum habitat size needed for a population to survive in a region. Habitats larger than the critical patch size allow a population to persist, while smaller habitats lead to extinction. The critical patch size of the 2-population model is consistent with that of the Fisher-Kolmogorov-Petrovsky-Piskunov equation, one of the first reaction-diffusion models proposed for GBM. The critical patch size may indicate that GBM tumors have a minimum size depending on the location in the brain. A theoretical relationship between the size of a GBM tumor at steady-state and its maximum cell density is also derived, which has potential applications for patient-specific parameter estimation based on magnetic resonance imaging data.
ContributorsHarris, Duane C. (Author) / Kuang, Yang (Thesis advisor) / Kostelich, Eric J. (Thesis advisor) / Preul, Mark C. (Committee member) / Crook, Sharon (Committee member) / Gardner, Carl (Committee member) / Arizona State University (Publisher)
Created2023
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Description
The most advanced social insects, the eusocial insects, form often large societies in which there is reproductive division of labor, queens and workers, have overlapping generations, and cooperative brood care where daughter workers remain in the nest with their queen mother and care for their siblings. The eusocial insects

The most advanced social insects, the eusocial insects, form often large societies in which there is reproductive division of labor, queens and workers, have overlapping generations, and cooperative brood care where daughter workers remain in the nest with their queen mother and care for their siblings. The eusocial insects are composed of representative species of bees and wasps, and all species of ants and termites. Much is known about their organizational structure, but remains to be discovered.

The success of social insects is dependent upon cooperative behavior and adaptive strategies shaped by natural selection that respond to internal or external conditions. The objective of my research was to investigate specific mechanisms that have helped shaped the structure of division of labor observed in social insect colonies, including age polyethism and nutrition, and phenomena known to increase colony survival such as egg cannibalism. I developed various Ordinary Differential Equation (ODE) models in which I applied dynamical, bifurcation, and sensitivity analysis to carefully study and visualize biological outcomes in social organisms to answer questions regarding the conditions under which a colony can survive. First, I investigated how the population and evolutionary dynamics of egg cannibalism and division of labor can promote colony survival. I then introduced a model of social conflict behavior to study the inclusion of different response functions that explore the benefits of cannibalistic behavior and how it contributes to age polyethism, the change in behavior of workers as they age, and its biological relevance. Finally, I introduced a model to investigate the importance of pollen nutritional status in a honeybee colony, how it affects population growth and influences division of labor within the worker caste. My results first reveal that both cannibalism and division of labor are adaptive strategies that increase the size of the worker population, and therefore, the persistence of the colony. I show the importance of food collection, consumption, and processing rates to promote good colony nutrition leading to the coexistence of brood and adult workers. Lastly, I show how taking into account seasonality for pollen collection improves the prediction of long term consequences.
ContributorsRodríguez Messan, Marisabel (Author) / Kang, Yun (Thesis advisor) / Castillo-Chavez, Carlos (Thesis advisor) / Kuang, Yang (Committee member) / Page Jr., Robert E (Committee member) / Gardner, Carl (Committee member) / Arizona State University (Publisher)
Created2018
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Description
This dissertation develops a second order accurate approximation to the magnetic resonance (MR) signal model used in the PARSE (Parameter Assessment by Retrieval from Single Encoding) method to recover information about the reciprocal of the spin-spin relaxation time function (R2*) and frequency offset function (w) in addition to the typical

This dissertation develops a second order accurate approximation to the magnetic resonance (MR) signal model used in the PARSE (Parameter Assessment by Retrieval from Single Encoding) method to recover information about the reciprocal of the spin-spin relaxation time function (R2*) and frequency offset function (w) in addition to the typical steady-state transverse magnetization (M) from single-shot magnetic resonance imaging (MRI) scans. Sparse regularization on an approximation to the edge map is used to solve the associated inverse problem. Several studies are carried out for both one- and two-dimensional test problems, including comparisons to the first order approximation method, as well as the first order approximation method with joint sparsity across multiple time windows enforced. The second order accurate model provides increased accuracy while reducing the amount of data required to reconstruct an image when compared to piecewise constant in time models. A key component of the proposed technique is the use of fast transforms for the forward evaluation. It is determined that the second order model is capable of providing accurate single-shot MRI reconstructions, but requires an adequate coverage of k-space to do so. Alternative data sampling schemes are investigated in an attempt to improve reconstruction with single-shot data, as current trajectories do not provide ideal k-space coverage for the proposed method.
ContributorsJesse, Aaron Mitchel (Author) / Platte, Rodrigo (Thesis advisor) / Gelb, Anne (Committee member) / Kostelich, Eric (Committee member) / Mittelmann, Hans (Committee member) / Moustaoui, Mohamed (Committee member) / Arizona State University (Publisher)
Created2019