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- All Subjects: Applied Mathematics
- Creators: Armbruster, Dieter
- Creators: Crook, Sharon
Description
Olfaction is an important sensory modality for behavior since odors inform animals of the presence of food, potential mates, and predators. The fruit fly, Drosophila melanogaster, is a favorable model organism for the investigation of the biophysical mechanisms that contribute to olfaction because its olfactory system is anatomically similar to but simpler than that of vertebrates. In the Drosophila olfactory system, sensory transduction takes place in olfactory receptor neurons housed in the antennae and maxillary palps on the front of the head. The first stage of olfactory processing resides in the antennal lobe, where the structural unit is the glomerulus. There are at least three classes of neurons in the antennal lobe - excitatory projection neurons, excitatory local neurons, and inhibitory local neurons. The arborizations of the local neurons are confined to the antennal lobe, and output from the antennal lobe is carried by projection neurons to higher regions of the brain. Different views exist of how circuits of the Drosophila antennal lobe translate input from the olfactory receptor neurons into projection neuron output. We construct a conductance based neuronal network model of the Drosophila antennal lobe with the aim of understanding possible mechanisms within the antennal lobe that account for the variety of projection neuron activity observed in experimental data. We explore possible outputs obtained from olfactory receptor neuron input that mimic experimental recordings under different connectivity paradigms. First, we develop realistic minimal cell models for the excitatory local neurons, inhibitory local neurons, and projections neurons based on experimental data for Drosophila channel kinetics, and explore the firing characteristics and mathematical structure of these models. We then investigate possible interglomerular and intraglomerular connectivity patterns in the Drosophila antennal lobe, where olfactory receptor neuron input to the antennal lobe is modeled with Poisson spike trains, and synaptic connections within the antennal lobe are mediated by chemical synapses and gap junctions as described in the Drosophila antennal lobe literature. Our simulation results show that inhibitory local neurons spread inhibition among all glomeruli, where projection neuron responses are decreased relatively uniformly for connections of synaptic strengths that are homogeneous. Also, in the case of homogeneous excitatory synaptic connections, the excitatory local neuron network facilitates odor detection in the presence of weak stimuli. Excitatory local neurons can spread excitation from projection neurons that receive more input from olfactory receptor neurons to projection neurons that receive less input from olfactory receptor neurons. For the parameter values for the network models associated with these results, eLNs decrease the ability of the network to discriminate among single odors.
ContributorsLuli, Dori (Author) / Crook, Sharon (Thesis advisor) / Baer, Steven (Committee member) / Castillo-Chavez, Carlos (Committee member) / Smith, Brian (Committee member) / Arizona State University (Publisher)
Created2013
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
Advances in experimental techniques have allowed for investigation of molecular dynamics at ever smaller temporal and spatial scales. There is currently a varied and growing body of literature which demonstrates the phenomenon of \emph{anomalous diffusion} in physics, engineering, and biology. In particular many diffusive type processes in the cell have been observed to follow a power law $\left \propto t^\alpha$ scaling of the mean square displacement of a particle. This contrasts with the expected linear behavior of particles undergoing normal diffusion. \emph{Anomalous sub-diffusion} ($\alpha<1$) has been attributed to factors such as cytoplasmic crowding of macromolecules, and trap-like structures in the subcellular environment non-linearly slowing the diffusion of molecules. Compared to normal diffusion, signaling molecules in these constrained spaces can be more concentrated at the source, and more diffuse at longer distances, potentially effecting the signalling dynamics. As diffusion at the cellular scale is a fundamental mechanism of cellular signaling and additionally is an implicit underlying mathematical assumption of many canonical models, a closer look at models of anomalous diffusion is warranted. Approaches in the literature include derivations of fractional differential diffusion equations (FDE) and continuous time random walks (CTRW). However these approaches are typically based on \emph{ad-hoc} assumptions on time- and space- jump distributions. We apply recent developments in asymptotic techniques on collisional kinetic equations to develop a FDE model of sub-diffusion due to trapping regions and investigate the nature of the space/time probability distributions assosiated with trapping regions. This approach both contrasts and compliments the stochastic CTRW approach by positing more physically realistic underlying assumptions on the motion of particles and their interactions with trapping regions, and additionally allowing varying assumptions to be applied individually to the traps and particle kinetics.
ContributorsHoleva, Thomas Matthew (Author) / Ringhofer, Christian (Thesis advisor) / Baer, Steve (Thesis advisor) / Crook, Sharon (Committee member) / Gardner, Carl (Committee member) / Taylor, Jesse (Committee member) / Arizona State University (Publisher)
Created2014
Description
This thesis presents a model for the buying behavior of consumers in a technology market. In this model, a potential consumer is not perfectly rational, but exhibits bounded rationality following the axioms of prospect theory: reference dependence, diminishing returns and loss sensitivity. To evaluate the products on different criteria, the analytic hierarchy process is used, which allows for relative comparisons. The analytic hierarchy process proposes that when making a choice between several alternatives, one should measure the products by comparing them relative to each other. This allows the user to put numbers to subjective criteria. Additionally, evidence suggests that a consumer will often consider not only their own evaluation of a product, but also the choices of other consumers. Thus, the model in this paper applies prospect theory to products with multiple attributes using word of mouth as a criteria in the evaluation.
ContributorsElkholy, Alexander (Author) / Armbruster, Dieter (Thesis advisor) / Kempf, Karl (Committee member) / Li, Hongmin (Committee member) / Arizona State University (Publisher)
Created2014
Description
Pre-Exposure Prophylaxis (PrEP) is any medical or public health procedure used before exposure to the disease causing agent, its purpose is to prevent, rather than treat or cure a disease. Most commonly, PrEP refers to an experimental HIV-prevention strategy that would use antiretrovirals to protect HIV-negative people from HIV infection. A deterministic mathematical model of HIV transmission is developed to evaluate the public-health impact of oral PrEP interventions, and to compare PrEP effectiveness with respect to different evaluation methods. The effects of demographic, behavioral, and epidemic parameters on the PrEP impact are studied in a multivariate sensitivity analysis. Most of the published models on HIV intervention impact assume that the number of individuals joining the sexually active population per year is constant or proportional to the total population. In the second part of this study, three models are presented and analyzed to study the PrEP intervention, with constant, linear, and logistic recruitment rates. How different demographic assumptions can affect the evaluation of PrEP is studied. When provided with data, often least square fitting or similar approaches can be used to determine a single set of approximated parameter values that make the model fit the data best. However, least square fitting only provides point estimates and does not provide information on how strongly the data supports these particular estimates. Therefore, in the third part of this study, Bayesian parameter estimation is applied on fitting ODE model to the related HIV data. Starting with a set of prior distributions for the parameters as initial guess, Bayes' formula can be applied to obtain a set of posterior distributions for the parameters which makes the model fit the observed data best. Evaluating the posterior distribution often requires the integration of high-dimensional functions, which is usually difficult to calculate numerically. Therefore, the Markov chain Monte Carlo (MCMC) method is used to approximate the posterior distribution.
ContributorsZhao, Yuqin (Author) / Kuang, Yang (Thesis advisor) / Taylor, Jesse (Committee member) / Armbruster, Dieter (Committee member) / Tang, Wenbo (Committee member) / Kang, Yun (Committee member) / Arizona State University (Publisher)
Created2014
Description
Bacteriophage (phage) are viruses that infect bacteria. Typical laboratory experiments show that in a chemostat containing phage and susceptible bacteria species, a mutant bacteria species will evolve. This mutant species is usually resistant to the phage infection and less competitive compared to the susceptible bacteria species. In some experiments, both susceptible and resistant bacteria species, as well as phage, can coexist at an equilibrium for hundreds of hours. The current research is inspired by these observations, and the goal is to establish a mathematical model and explore sufficient and necessary conditions for the coexistence. In this dissertation a model with infinite distributed delay terms based on some existing work is established. A rigorous analysis of the well-posedness of this model is provided, and it is proved that the susceptible bacteria persist. To study the persistence of phage species, a "Phage Reproduction Number" (PRN) is defined. The mathematical analysis shows phage persist if PRN > 1 and vanish if PRN < 1. A sufficient condition and a necessary condition for persistence of resistant bacteria are given. The persistence of the phage is essential for the persistence of resistant bacteria. Also, the resistant bacteria persist if its fitness is the same as the susceptible bacteria and if PRN > 1. A special case of the general model leads to a system of ordinary differential equations, for which numerical simulation results are presented.
ContributorsHan, Zhun (Author) / Smith, Hal (Thesis advisor) / Armbruster, Dieter (Committee member) / Kawski, Matthias (Committee member) / Kuang, Yang (Committee member) / Thieme, Horst (Committee member) / Arizona State University (Publisher)
Created2012
Description
Modern measurement schemes for linear dynamical systems are typically designed so that different sensors can be scheduled to be used at each time step. To determine which sensors to use, various metrics have been suggested. One possible such metric is the observability of the system. Observability is a binary condition determining whether a finite number of measurements suffice to recover the initial state. However to employ observability for sensor scheduling, the binary definition needs to be expanded so that one can measure how observable a system is with a particular measurement scheme, i.e. one needs a metric of observability. Most methods utilizing an observability metric are about sensor selection and not for sensor scheduling. In this dissertation we present a new approach to utilize the observability for sensor scheduling by employing the condition number of the observability matrix as the metric and using column subset selection to create an algorithm to choose which sensors to use at each time step. To this end we use a rank revealing QR factorization algorithm to select sensors. Several numerical experiments are used to demonstrate the performance of the proposed scheme.
ContributorsIlkturk, Utku (Author) / Gelb, Anne (Thesis advisor) / Platte, Rodrigo (Thesis advisor) / Cochran, Douglas (Committee member) / Renaut, Rosemary (Committee member) / Armbruster, Dieter (Committee member) / Arizona State University (Publisher)
Created2015
Description
Factory production is stochastic in nature with time varying input and output processes that are non-stationary stochastic processes. Hence, the principle quantities of interest are random variables. Typical modeling of such behavior involves numerical simulation and statistical analysis. A deterministic closure model leading to a second order model for the product density and product speed has previously been proposed. The resulting partial differential equations (PDE) are compared to discrete event simulations (DES) that simulate factory production as a time dependent M/M/1 queuing system. Three fundamental scenarios for the time dependent influx are studied: An instant step up/down of the mean arrival rate; an exponential step up/down of the mean arrival rate; and periodic variation of the mean arrival rate. It is shown that the second order model, in general, yields significant improvement over current first order models. Specifically, the agreement between the DES and the PDE for the step up and for periodic forcing that is not too rapid is very good. Adding diffusion to the PDE further improves the agreement. The analysis also points to fundamental open issues regarding the deterministic modeling of low signal-to-noise ratio for some stochastic processes and the possibility of resonance in deterministic models that is not present in the original stochastic process.
ContributorsWienke, Matthew (Author) / Armbruster, Dieter (Thesis advisor) / Jones, Donald (Committee member) / Platte, Rodrigo (Committee member) / Gardner, Carl (Committee member) / Ringhofer, Christian (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
The Kuramoto model is an archetypal model for studying synchronization in groups
of nonidentical oscillators where oscillators are imbued with their own frequency and
coupled with other oscillators though a network of interactions. As the coupling
strength increases, there is a bifurcation to complete synchronization where all oscillators
move with the same frequency and show a collective rhythm. Kuramoto-like
dynamics are considered a relevant model for instabilities of the AC-power grid which
operates in synchrony under standard conditions but exhibits, in a state of failure,
segmentation of the grid into desynchronized clusters.
In this dissertation the minimum coupling strength required to ensure total frequency
synchronization in a Kuramoto system, called the critical coupling, is investigated.
For coupling strength below the critical coupling, clusters of oscillators form
where oscillators within a cluster are on average oscillating with the same long-term
frequency. A unified order parameter based approach is developed to create approximations
of the critical coupling. Some of the new approximations provide strict lower
bounds for the critical coupling. In addition, these approximations allow for predictions
of the partially synchronized clusters that emerge in the bifurcation from the
synchronized state.
Merging the order parameter approach with graph theoretical concepts leads to a
characterization of this bifurcation as a weighted graph partitioning problem on an
arbitrary networks which then leads to an optimization problem that can efficiently
estimate the partially synchronized clusters. Numerical experiments on random Kuramoto
systems show the high accuracy of these methods. An interpretation of the
methods in the context of power systems is provided.
of nonidentical oscillators where oscillators are imbued with their own frequency and
coupled with other oscillators though a network of interactions. As the coupling
strength increases, there is a bifurcation to complete synchronization where all oscillators
move with the same frequency and show a collective rhythm. Kuramoto-like
dynamics are considered a relevant model for instabilities of the AC-power grid which
operates in synchrony under standard conditions but exhibits, in a state of failure,
segmentation of the grid into desynchronized clusters.
In this dissertation the minimum coupling strength required to ensure total frequency
synchronization in a Kuramoto system, called the critical coupling, is investigated.
For coupling strength below the critical coupling, clusters of oscillators form
where oscillators within a cluster are on average oscillating with the same long-term
frequency. A unified order parameter based approach is developed to create approximations
of the critical coupling. Some of the new approximations provide strict lower
bounds for the critical coupling. In addition, these approximations allow for predictions
of the partially synchronized clusters that emerge in the bifurcation from the
synchronized state.
Merging the order parameter approach with graph theoretical concepts leads to a
characterization of this bifurcation as a weighted graph partitioning problem on an
arbitrary networks which then leads to an optimization problem that can efficiently
estimate the partially synchronized clusters. Numerical experiments on random Kuramoto
systems show the high accuracy of these methods. An interpretation of the
methods in the context of power systems is provided.
ContributorsGilg, Brady (Author) / Armbruster, Dieter (Thesis advisor) / Mittelmann, Hans (Committee member) / Scaglione, Anna (Committee member) / Strogatz, Steven (Committee member) / Welfert, Bruno (Committee member) / Arizona State University (Publisher)
Created2018