Graduation Semester and Year

Spring 2024

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Mathematics

Department

Mathematics

First Advisor

Souvik Roy

Abstract

In this thesis, we employ optimal control frameworks in two distinct contexts: Human immunodeficiency virus (HIV) and esophageal cancer. For HIV, we introduce a comprehensive data-driven nonlinear optimization framework designed for personalized therapies. This framework utilizes a deterministic in-host nonlinear ordinary differential equation (ODE) model and formulates two optimization problems using individual patient data. The first problem focuses on estimating patient-specific parameters through constrained optimization, while the second problem determines optimal combination therapies to reduce viral load to undetectable levels. Several numerical experiments suggest that our framework can provide a robust and effective optimal dosages with lower toxicity levels to control HIV.

In esophageal cancer, we present an innovative approach to model and control aberrant signaling pathways. This involves leveraging an It\^o stochastic process to capture signaling pathway dynamics, governed by a degenerate Fokker-Planck partial differential equation. Our study proposes a refined treatment strategy targeting aberrant signaling pathways, specifically focusing on epidermal growth factor (EGF) pathways. This strategy includes developing a pharmacokinetic model considering pathway heterogeneities, preceded by constrained optimization to obtain model parameters from patient data. Subsequently, we propose a personalized optimal treatment strategy targeting aberrant EGF using a non-smooth open-loop control for a stochastic process modeled by the FP equation. The solution to these problems is characterized within the framework of Pontryagin's minimum principle (PMP), and the optimization problem is solved using a sequential quadratic Hamiltonian (SQH) method. Experimental results are presented to validate the proposed framework successfully.

Keywords

optimal control, parameter estimation, non-linear conjugate gradient, Pontryagin's minimum principle, HIV, esophageal cancer

Disciplines

Control Theory | Dynamical Systems | Non-linear Dynamics | Ordinary Differential Equations and Applied Dynamics | Partial Differential Equations

License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.