K. Renee Fister

Optimal control applied to cell-cycle-specific cancer chemotherapy

We propose a mathematical model for the growth of cell-cycle-specific dose limiting bone marrow. In an attempt to determine effective methods of treatment without overdestruction of the bone marrow we implement optimal control theory. We design the control functional to maximize both the bone marrow mass and the dose over the treatment interval. Next we show that an optimal control exists for this problem, and then we characterize our optimal control in terms of the solutions to the optimality system, which is the state system coupled with the adjoint system. We show that the optimality system is unique for suitably small time intervals. Finally, we analyze the optimal control and the optimality system using numerical techniques. This allows us to suggest optimal methods of treatment that prevent excessive destruction of the bone marrow based on the specific weights in our objective functional.

Modeling optimal intervention strategies for cholera.

While cholera has been a recognized disease for two centuries, there is no strategy for its effective control. We formulate a mathematical model to include essential components such as a hyperinfectious, short-lived bacterial state, a separate class for mild human infections, and waning disease immunity. A new result quantifies contributions to the basic reproductive number from multiple infectious classes. Using optimal control theory, parameter sensitivity analysis, and numerical simulations, a cost-effective balance of multiple intervention methods is compared for two endemic populations. Results provide a framework for designing cost-effective strategies for diseases with multiple intervention methods.

Optimal Control Applied to Competing Chemotherapeutic Cell-Kill Strategies

Optimal control techniques are used to develop optimal strategies for chemotherapy. In particular, we investigate the qualitative differences between three different cell-kill models: log-kill hypo...

Mathematical Model Creation for Cancer Chemo-Immunotherapy

One of the most challenging tasks in constructing a mathematical model of cancer treatment is the calculation of biological parameters from empirical data. This task becomes increasingly difficult if a model involves several cell populations and treatment modalities. A sophisticated model constructed by de Pillis et al., Mixed immunotherapy and chemotherapy of tumours: Modelling, applications and biological interpretations, J. Theor. Biol. 238 (2006), pp. 841‐862; involves tumour cells, specific and non-specific immune cells (natural killer (NK) cells, CD8 þ T cells and other lymphocytes) and employs chemotherapy and two types of immunotherapy (IL-2 supplementation and CD8 þ T-cell infusion) as treatment modalities. Despite the overall success of the aforementioned model, the problem of illustrating the effects of IL-2 on a growing tumour remains open. In this paper, we update the model of de Pillisetal. and then carefully identify appropriate values for the parameters of the new model according to recent empirical data. We determine new NK and tumour antigen-activated CD8 þ T-cell count equilibrium values; we complete IL-2 dynamics; and we modify the model in de Pillisetal. to allow for endogenous IL-2 production, IL-2-stimulated NK cell proliferation and IL-2-dependent CD8 þ T-cell self-regulations. Finally, we show that the potential patient-specific efficacy

Mathematics Instruction and the Tablet PC.

The use of tablet PCs in teaching is a relatively new phenomenon. A cross between a notebook computer and a personal digital assistant (PDA), the tablet PC has all of the features of a notebook with the additional capability that the screen can also be used for input. Tablet PCs are usually equipped with a stylus that allows the user to write on the screen. Handwriting recognition software converts this input into text for use with software such as internet browsers and email programs. As an educational tool, two of the most important features of the tablet PC are annotation and wireless communication. The annotation feature allows the user to write on almost any document much as one would annotate a printout of the same document. The wireless communication feature allows tablet PCs to share information with one another. The advantages of these features and their impact on the Murray State University (MSU) classroom will be discussed in the evaluation section.

Optimal control of insects through sterile insect release and habitat modification

This paper develops an optimal control framework for an ordinary differential equation model to investigate the introduction of sterile mosquitoes to reduce the incidence of mosquito-borne diseases. Existence of a solution given an optimal strategy and the optimal control is determined in association with the negative effects of the disease on the population while minimizing the cost due to this control mechanism. Numerical simulations have shown the importance of effects of the bounds on the release of sterile mosquitoes and the bounds on the likelihood of egg maturation. The optimal strategy is to maximize the use of habitat modification or insecticide. A combination of techniques leads to a more rapid elimination of the wild mosquito population.

Optimal control of harvesting coupled with boundary control in a predator—prey system

We consider boundary control and control via harvesting in a parabolic predator—prey system for a bounded region. The boundary control depicts the relationship between the boundary environment and the possibly harmful species. In addition, a proportion of the predator is harvested for profit. We choose to maximize the objective functional which incorporates the amount of the prey and the revenue of harvesting of the predator less the economic cost of sustaining a satisfactory boundary habitat and the cost due to the harvesting component. Moreover, we characterize the unique optimal control in terms of the solution to the optimality system, which is the state system coupled with the adjoint system.We consider boundary control and control via harvesting in a parabolic predator—prey system for a bounded region. The boundary control depicts the relationship between the boundary environment and the possibly harmful species. In addition, a proportion of the predator is harvested for profit. We choose to maximize the objective functional which incorporates the amount of the prey and the revenue of harvesting of the predator less the economic cost of sustaining a satisfactory boundary habitat and the cost due to the harvesting component. Moreover, we characterize the unique optimal control in terms of the solution to the optimality system, which is the state system coupled with the adjoint system.

The identification of a time dependent sorption parameter from soil column experiments

Soil column studies are used frequently in seeking to understand the behavior of a particular contaminant in a saturated homogeneous soil of a given type. The concentration of the contaminant is modeled by a parabolic partial differential equation. We seek to identify the sorption partitioning coefficient as a function of time from limited boundary data. We discuss an output least squares formulation of the problem with Tikhonov regularization. We explicitly characterize a source condition that determines the rate of convergence of the method. Numerical examples are presented.

Identification of a chemotactic sensitivity in a coupled system

Chemotaxis is the process by which cells behave in a way that follows the chemical gradient. Applications to bacteria growth, tissue inflammation and vascular tumours provide a focus on optimization strategies. Experiments can characterize the form of possible chemotactic sensitivities. This paper addresses the recovery of the chemotactic sensitivity from these experiments while allowing for non-linear dependence of the parameter on the state variables. The existence of solutions to the forward problem is analysed. The identification of a chemotactic parameter is determined by inverse problem techniques. Tikhonov regularization is investigated and appropriate convergence results are obtained. Numerical results of concentration-dependent chemotactic terms are explored.

Optimal Control of Vaccination in an Age-Structured Cholera Model

A cholera model with continuous age structure is given as a system of hyperbolic (first-order) partial differential equations (PDEs) in combination with ordinary differential equations. Asymptomatic infected and susceptibles with partial immunity are included in this epidemiology model with vaccination rate as a control; minimizing the symptomatic infecteds while minimizing the cost of the vaccinations represents the goal. With the method of characteristics and a fixed point argument, the existence of a solution to our nonlinear state system is achieved. The representation and existence of a unique optimal control are derived. The steps to justify the optimal control results for such a system with first order PDEs are given. Numerical results illustrate the effect of age structure on optimal vaccination rates.