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Combination therapy has shown to improve success for cancer treatment. Oncolytic virotherapy is cancer treatment that uses engineered viruses to specifically infect and kill cancer cells, without harming healthy cells. Immunotherapy boosts the body's natural defenses towards cancer. The combination of oncolytic virotherapy and immunotherapy is explored through deterministic systems of nonlinear differential equations, constructed to match experimental data for murine melanoma. Mathematical analysis was done in order to gain insight on the relationship between cancer, viruses and immune response. One extension of the model focuses on clinical needs, with the underlying goal to seek optimal treatment regimens; for both frequency and dose quantity. The models in this work were first used to estimate parameters from preclinical experimental data, to identify biologically realistic parameter values. Insight gained from the mathematical analysis in the first model, allowed for numerical analysis to explore optimal treatment regimens of combination oncolytic virotherapy and dendritic vaccinations. Permutations accounting for treatment scheduled were done to find regimens that reduce tumor size. Observations from the produced data lead to in silico exploration of immune-viral interactions. Results suggest under optimal settings, combination treatment works better than monotherapy of either type. The most optimal result suggests treatment over a longer period of time, with fractioned doses, while reducing the total dendritic vaccination quantity, and maintaining the maximum virotherapy used in the experimental work.
ContributorsSummer, Ilyssa Aimee (Author) / Castillo-Chavez, Carlos (Thesis advisor) / Nagy, John (Thesis advisor) / Mubayi, Anuj (Committee member) / Kang, Yun (Committee member) / Arizona State University (Publisher)
Created2016
Description
The decline of honeybee colonies around the world has been linked to the presence of the Varroa destructor, a mite acting as a virus vector for the Acute Bee Paralysis Virus. We developed a model of the infestation of the Apis melliifera honeybee colony by the Acute Bee Paralysis Virus, which is transmitted by the parasitic Varroa destructor. This is a four dimensional system of nonlinear ODE's for healthy and virus infected bees, total number of mites in the colony and number of mites that carry the virus. The Acute Bee Paralysis Virus can be transmitted between infected and uninfected bees, infected mite to adult bee, infected bee to phoretic mite, and reproductive mites to bee brood. This model is studied with analytical techniques deriving the conditions under which the bee colony can fight off an Acute Bee Paralysis Virus epidemic.
ContributorsDavis, Talia Lasandra (Author) / Kang, Yun (Thesis director) / Lanchier, Nicolas (Committee member) / Moore, Marianne (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
Honeybees are important pollinators worldwide and pollinate about one-third of the food we consume. Recently though, honeybee colonies have been under increasing stress due to changing environments, pesticides, mites, and viruses, which has increased the incidence of
colony collapse. This paper aims to understand how these different factors contribute to the decline of honeybee populations by using two separate approaches: data analysis and mathematical modeling. The data analysis examines the relative impacts of mites, pollen, mites, and viruses on honeybee populations and colony collapse. From the data, low initial bee populations lead to collapse in September while mites and viruses can lead to collapse in December. Feeding bee colonies also has a mixed effect, where it increases both bee and mite populations. For the model, we focus on the population dynamics of the honeybee-mite interaction. Using a system of delay differential equations with five population components, we find that bee colonies can collapse from mites, coexist with mites, and survive without them. As long as bees produce more pupa than the death rate of pupa and mites produce enough phoretic mites compared to their death rates, bees and mites can coexist. Thus, it is possible for honeybee colonies to withstand mites, but if the parasitism is too large, the colony will collapse. Provided
this equilibrium exists, the addition of mites leads to the colony moving to the interior equilibrium. Additionally, population oscillations are persistent if they occur and are connected to the interior equilibrium. Certain parameter values destabilize bee populations, leading to large
oscillations and even collapse. From these parameters, we can develop approaches that can help us prevent honeybee colony collapse before it occurs.
colony collapse. This paper aims to understand how these different factors contribute to the decline of honeybee populations by using two separate approaches: data analysis and mathematical modeling. The data analysis examines the relative impacts of mites, pollen, mites, and viruses on honeybee populations and colony collapse. From the data, low initial bee populations lead to collapse in September while mites and viruses can lead to collapse in December. Feeding bee colonies also has a mixed effect, where it increases both bee and mite populations. For the model, we focus on the population dynamics of the honeybee-mite interaction. Using a system of delay differential equations with five population components, we find that bee colonies can collapse from mites, coexist with mites, and survive without them. As long as bees produce more pupa than the death rate of pupa and mites produce enough phoretic mites compared to their death rates, bees and mites can coexist. Thus, it is possible for honeybee colonies to withstand mites, but if the parasitism is too large, the colony will collapse. Provided
this equilibrium exists, the addition of mites leads to the colony moving to the interior equilibrium. Additionally, population oscillations are persistent if they occur and are connected to the interior equilibrium. Certain parameter values destabilize bee populations, leading to large
oscillations and even collapse. From these parameters, we can develop approaches that can help us prevent honeybee colony collapse before it occurs.
ContributorsSweeney, Brian Felix (Author) / Kang, Yun (Thesis director) / Mubayi, Anuj (Committee member) / College of Integrative Sciences and Arts (Contributor) / Economics Program in CLAS (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05