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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
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
Dividing the plane in half leaves every border point of one region a border point of both regions. Can we divide up the plane into three or more regions such that any point on the boundary of at least one region is on the border of all the regions? In

Dividing the plane in half leaves every border point of one region a border point of both regions. Can we divide up the plane into three or more regions such that any point on the boundary of at least one region is on the border of all the regions? In fact, it is possible to design a dynamical system for which the basins of attractions have this Wada property. In certain circumstances, both the Hénon map, a simple system, and the forced damped pendulum, a physical model, produce Wada basins.
ContributorsWhitehurst, Ryan David (Author) / Kostelich, Eric (Thesis director) / Jones, Donald (Committee member) / Armbruster, Dieter (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2013-05
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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
A semi-implicit, fourth-order time-filtered leapfrog numerical scheme is investigated for accuracy and stability, and applied to several test cases, including one-dimensional advection and diffusion, the anelastic equations to simulate the Kelvin-Helmholtz instability, and the global shallow water spectral model to simulate the nonlinear evolution of twin tropical cyclones. The leapfrog

A semi-implicit, fourth-order time-filtered leapfrog numerical scheme is investigated for accuracy and stability, and applied to several test cases, including one-dimensional advection and diffusion, the anelastic equations to simulate the Kelvin-Helmholtz instability, and the global shallow water spectral model to simulate the nonlinear evolution of twin tropical cyclones. The leapfrog scheme leads to computational modes in the solutions to highly nonlinear systems, and time-filters are often used to damp these modes. The proposed filter damps the computational modes without appreciably degrading the physical mode. Its performance in these metrics is superior to the second-order time-filtered leapfrog scheme developed by Robert and Asselin.
Created2016-05
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Description
Chebfun is a collection of algorithms and an open-source software system in object-oriented Matlab that extends familiar powerful methods of numerical computation involving numbers to continuous or piecewise-continuous functions. The success of this strategy is based on the mathematical fact that smooth functions can be represented very efficiently by polynomial

Chebfun is a collection of algorithms and an open-source software system in object-oriented Matlab that extends familiar powerful methods of numerical computation involving numbers to continuous or piecewise-continuous functions. The success of this strategy is based on the mathematical fact that smooth functions can be represented very efficiently by polynomial interpolation at Chebyshev points or by trigonometric interpolation at equispaced points for periodic functions. More recently, the system has been extended to handle bivariate functions and vector fields. These two new classes of objects are called Chebfun2 and Chebfun2v, respectively. We will show that Chebfun2 and Chebfun2v, and can be used to accurately and efficiently perform various computations on parametric surfaces in two or three dimensions, including path trajectories and mean and Gaussian curvatures. More advanced surface computations such as mean curvature flows are also explored. This is also the first work to use the newly implemented trigonometric representation, namely Trigfun, for computations on surfaces.
ContributorsPage-Bottorff, Courtney Michelle (Author) / Platte, Rodrigo (Thesis director) / Kostelich, Eric (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
High-dimensional systems are difficult to model and predict. The underlying mechanisms of such systems are too complex to be fully understood with limited theoretical knowledge and/or physical measurements. Nevertheless, redcued-order models have been widely used to study high-dimensional systems, because they are practical and efficient to develop and implement. Although

High-dimensional systems are difficult to model and predict. The underlying mechanisms of such systems are too complex to be fully understood with limited theoretical knowledge and/or physical measurements. Nevertheless, redcued-order models have been widely used to study high-dimensional systems, because they are practical and efficient to develop and implement. Although model errors (biases) are inevitable for reduced-order models, these models can still be proven useful to develop real-world applications. Evaluation and validation for idealized models are indispensable to serve the mission of developing useful applications. Data assimilation and uncertainty quantification can provide a way to assess the performance of a reduced-order model. Real data and a dynamical model are combined together in a data assimilation framework to generate corrected model forecasts of a system. Uncertainties in model forecasts and observations are also quantified in a data assimilation cycle to provide optimal updates that are representative of the real dynamics. In this research, data assimilation is applied to assess the performance of two reduced-order models. The first model is developed for predicting prostate cancer treatment response under intermittent androgen suppression therapy. A sequential data assimilation scheme, the ensemble Kalman filter (EnKF), is used to quantify uncertainties in model predictions using clinical data of individual patients provided by Vancouver Prostate Center. The second model is developed to study what causes the changes of the state of stratospheric polar vortex. Two data assimilation schemes: EnKF and ES-MDA (ensemble smoother with multiple data assimilation), are used to validate the qualitative properties of the model using ECMWF (European Center for Medium-Range Weather Forecasts) reanalysis data. In both studies, the reduced-order model is able to reproduce the data patterns and provide insights to understand the underlying mechanism. However, significant model errors are also diagnosed for both models from the results of data assimilation schemes, which suggests specific improvements of the reduced-order models.
ContributorsWu, Zhimin (Author) / Kostelich, Eric (Thesis advisor) / Moustaoui, Mohamed (Thesis advisor) / Jones, Chris (Committee member) / Espanol, Malena (Committee member) / Platte, Rodrigo (Committee member) / Arizona State University (Publisher)
Created2021
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Description
Synthetic biology (SB) has become an important field of science focusing on designing and engineering new biological parts and systems, or re-designing existing biological systems for useful purposes. The dramatic growth of SB throughout the past two decades has not only provided us numerous achievements, but also brought us more

Synthetic biology (SB) has become an important field of science focusing on designing and engineering new biological parts and systems, or re-designing existing biological systems for useful purposes. The dramatic growth of SB throughout the past two decades has not only provided us numerous achievements, but also brought us more timely and underexplored problems. In SB's entire history, mathematical modeling has always been an indispensable approach to predict the experimental outcomes, improve experimental design and obtain mechanism-understanding of the biological systems. \textit{Escherichia coli} (\textit{E. coli}) is one of the most important experimental platforms, its growth dynamics is the major research objective in this dissertation. Chapter 2 employs a reaction-diffusion model to predict the \textit{E. coli} colony growth on a semi-solid agar plate under multiple controls. In that chapter, a density-dependent diffusion model with non-monotonic growth to capture the colony's non-linear growth profile is introduced. Findings of the new model to experimental data are compared and contrasted with those from other proposed models. In addition, the cross-sectional profile of the colony are computed and compared with experimental data. \textit{E. coli} colony is also used to perform spatial patterns driven by designed gene circuits. In Chapter 3, a gene circuit (MINPAC) and its corresponding pattern formation results are presented. Specifically, a series of partial differential equation (PDE) models are developed to describe the pattern formation driven by the MINPAC circuit. Model simulations of the patterns based on different experimental conditions and numerical analysis of the models to obtain a deeper understanding of the mechanisms are performed and discussed. Mathematical analysis of the simplified models, including traveling wave analysis and local stability analysis, is also presented and used to explore the control strategies of the pattern formation. The interaction between the gene circuit and the host \textit{E. coli} may be crucial and even greatly affect the experimental outcomes. Chapter 4 focuses on the growth feedback between the circuit and the host cell under different nutrient conditions. Two ordinary differential equation (ODE) models are developed to describe such feedback with nutrient variation. Preliminary results on data fitting using both two models and the model dynamical analysis are included.
ContributorsHe, Changhan (Author) / Kuang, Yang (Thesis advisor) / Wang, Xiao (Committee member) / Kostelich, Eric (Committee member) / Tian, Xiaojun (Committee member) / Gumel, Abba (Committee member) / Arizona State University (Publisher)
Created2021
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Description
A pneumonia-like illness emerged late in 2019 (coined COVID-19), caused by SARSCoV-2, causing a devastating global pandemic on a scale never before seen sincethe 1918/1919 influenza pandemic. This dissertation contributes in providing deeper qualitative insights into the transmission dynamics and control of the disease in the United States. A basic mathematical model,

A pneumonia-like illness emerged late in 2019 (coined COVID-19), caused by SARSCoV-2, causing a devastating global pandemic on a scale never before seen sincethe 1918/1919 influenza pandemic. This dissertation contributes in providing deeper qualitative insights into the transmission dynamics and control of the disease in the United States. A basic mathematical model, which incorporates the key pertinent epidemiological features of SARS-CoV-2 and fitted using observed COVID-19 data, was designed and used to assess the population-level impacts of vaccination and face mask usage in mitigating the burden of the pandemic in the United States. Conditions for the existence and asymptotic stability of the various equilibria of the model were derived. The model was shown to undergo a vaccine-induced backward bifurcation when the associated reproduction number is less than one. Conditions for achieving vaccine-derived herd immunity were derived for three of the four FDA-approved vaccines (namely Pfizer, Moderna and Johnson & Johnson vaccine), and the vaccination coverage level needed to achieve it decreases with increasing coverage of moderately and highly-effective face masks. It was also shown that using face masks as a singular intervention strategy could lead to the elimination of the pandemic if moderate or highly-effective masks are prioritized and pandemic elimination prospects are greatly enhanced if the vaccination program is combined with a face mask use strategy that emphasizes the use of moderate to highly-effective masks with at least moderate coverage. The model was extended in Chapter 3 to allow for the assessment of the impacts of waning and boosting of vaccine-derived and natural immunity against the BA.1 Omicron variant of SARS-CoV-2. It was shown that vaccine-derived herd immunity can be achieved in the United States via a vaccination-boosting strategy which entails fully vaccinating at least 72% of the susceptible populace. Boosting of vaccine-derived immunity was shown to be more beneficial than boosting of natural immunity. Overall, this study showed that the prospects of the elimination of the pandemic in the United States were highly promising using the two intervention measures.
ContributorsSafdar, Salman (Author) / Gumel, Abba (Thesis advisor) / Kostelich, Eric (Committee member) / Kang, Yun (Committee member) / Fricks, John (Committee member) / Espanol, Malena (Committee member) / Arizona State University (Publisher)
Created2023
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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