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- All Subjects: opinion dynamics
- All Subjects: Retinitis pigmentosa
- Creators: Camacho, Erika
Description
Patients suffering from Retinitis Pigmentosa (RP), the most common type of inherited retinal degeneration, experience irreversible vision loss due to photoreceptor degeneration. The preservation of cone photoreceptors has been deemed medically relevant as a therapy aimed at preventing blindness in patients with RP. Cones rely on aerobic glycolysis to supply the metabolites necessary for outer segment (OS) renewal and maintenance. The rod-derived cone viability factor (RdCVF), a protein secreted by the rod photoreceptors that preserves the cones, accelerates the flow of glucose into the cone cell stimulating aerobic glycolysis. This dissertation presents and analyzes ordinary differential equation (ODE) models of cellular and molecular level photoreceptor interactions in health and disease to examine mechanisms leading to blindness in patients with RP.
First, a mathematical model composed of four ODEs is formulated to investigate the progression of RP, accounting for the new understanding of RdCVF’s role in enhancing cone survival. A mathematical analysis is performed, and stability and bifurcation analyses are used to explore various pathways to blindness. Experimental data are used for parameter estimation and model validation. The numerical results are framed in terms of four stages in the progression of RP. Sensitivity analysis is used to determine mechanisms that have a significant affect on the cones at each stage of RP. Utilizing a non-dimensional form of the RP model, a numerical bifurcation analysis via MATCONT revealed the existence of stable limit cycles at two stages of RP.
Next, a novel eleven dimensional ODE model of molecular and cellular level interactions is described. The subsequent analysis is used to uncover mechanisms that affect cone photoreceptor functionality and vitality. Preliminary simulations show the existence of oscillatory behavior which is anticipated when all processes are functioning properly. Additional simulations are carried out to explore the impact of a reduction in the concentration of RdCVF coupled with disruption in the metabolism associated with cone OS shedding, and confirms cone-on-rod reliance. The simulation results are compared with experimental data. Finally, four cases are considered, and a sensitivity analysis is performed to reveal mechanisms that significantly impact the cones in each case.
First, a mathematical model composed of four ODEs is formulated to investigate the progression of RP, accounting for the new understanding of RdCVF’s role in enhancing cone survival. A mathematical analysis is performed, and stability and bifurcation analyses are used to explore various pathways to blindness. Experimental data are used for parameter estimation and model validation. The numerical results are framed in terms of four stages in the progression of RP. Sensitivity analysis is used to determine mechanisms that have a significant affect on the cones at each stage of RP. Utilizing a non-dimensional form of the RP model, a numerical bifurcation analysis via MATCONT revealed the existence of stable limit cycles at two stages of RP.
Next, a novel eleven dimensional ODE model of molecular and cellular level interactions is described. The subsequent analysis is used to uncover mechanisms that affect cone photoreceptor functionality and vitality. Preliminary simulations show the existence of oscillatory behavior which is anticipated when all processes are functioning properly. Additional simulations are carried out to explore the impact of a reduction in the concentration of RdCVF coupled with disruption in the metabolism associated with cone OS shedding, and confirms cone-on-rod reliance. The simulation results are compared with experimental data. Finally, four cases are considered, and a sensitivity analysis is performed to reveal mechanisms that significantly impact the cones in each case.
ContributorsBrager, Danielle Christine (Author) / Camacho, Erika (Thesis advisor) / Wirkus, Stephen (Thesis advisor) / Fricks, John (Committee member) / Gardner, Carl (Committee member) / Platte, Rodrigo (Committee member) / Arizona State University (Publisher)
Created2020
Description
This dissertation consists of three papers about opinion dynamics. The first paper is in collaboration with Prof. Lanchier while the other two papers are individual works.
Two models are introduced and studied analytically: the Deffuant model and the Hegselmann-Krause~(HK) model.
The main difference between the two models is that the Deffuant dynamics consists of pairwise interactions whereas the HK dynamics consists of group interactions.
Translated into graph, each vertex stands for an agent in both models.
In the Deffuant model, two graphs are combined: the social graph and the opinion graph.
The social graph is assumed to be a general finite connected graph where each edge is interpreted as a social link, such as a friendship relationship, between two agents.
At each time step, two social neighbors are randomly selected and interact if and only if their opinion distance does not exceed some confidence threshold, which results in the neighbors' opinions getting closer to each other.
The main result about the Deffuant model is the derivation of a positive lower bound for the probability of consensus that is independent of the size and topology of the social graph but depends on the confidence threshold, the choice of the opinion space and the initial distribution. For the HK model, agent~$i$ updates its opinion~$x_i$ by taking the average opinion of its neighbors, defined as the set of agents with opinion at most~$\epsilon$ apart from~$x_i$. Here,~$\epsilon > 0$ is a confidence threshold.
There are two types of HK models: the synchronous and the asynchronous HK models.
In the former, all the agents update their opinion simultaneously at each time step, whereas in the latter, only one agent is selected uniformly at random to update its opinion at each time step.
The mixed model is a variant of the HK model in which each agent can choose its degree of stubbornness and mix its opinion with the average opinion of its neighbors.
The main results of this dissertation about HK models show conditions under which the asymptotic stability holds or a consensus can be achieved, and give a positive lower bound for the probability of consensus and, in the one-dimensional case, an upper bound for the probability of consensus.
I demonstrate the bounds for the probability of consensus on a unit cube and a unit interval.
ContributorsLi, Hsin-Lun (Author) / Lanchier, Nicolas (Thesis advisor) / Camacho, Erika (Committee member) / Czygrinow, Andrzej (Committee member) / Fishel, Susanna (Committee member) / Motsch, Sebastien (Committee member) / Arizona State University (Publisher)
Created2021