Date of Award

Summer 2004

Document Type

Thesis - Restricted

Degree Name

Master of Science (MS)

Department

Biomedical Engineering

First Advisor

Audi, Said H.

Second Advisor

Merker, Marilyn P.

Third Advisor

Krenz, Gary S.

Abstract

This thesis describes the development of a user-friendly numerical and statistical computer package for (i) testing hypotheses regarding the contributions of various pulmonary endothelial cellular redox processes to the extracellular redox status of redox active compounds, including quinones, and (ii) estimating kinetic parameters descriptive of these processes. Chapter 1 provides the background and motivation for developing the user friendly package and states the specific goals and objectives of the thesis. Chapter 2 describes the redox kinetic data measured following the addition of the model quinione duroquinone (DQ) or its two-electron reduction product, durohydroquinone (DQH2), to cultured endothelial cells under various experimental conditions, and the kinetic model used for quantitative interpretation of the data. The data and the kinetic model are used as a basis to illustrate the methodology involved in designing and developing the user-friendly package. Chapter 3 provides a detailed description of the various steps involved in designing the user-friendly modeling package which is implemented using MATLAB, version 6.5, (The Math Works Inc., Natick, MA). This platform has a vast collection of computational algorithms, various toolboxes that are comprehensive collections of MATLAB functions, and a convenient environment to build graphical user interfaces (GUI). Chapter 4 illustrates the utility of the package by reanalyzing previously published DQ/DQH2 kinetic data under various experimental conditions and comparing the estimated values of the model parameters with the published values. The tool is also used to further our understanding on the effect of oxidative stress ( e.g., hyperoxia) on endothelial redox metabolism and to design experimental protocols for targeting pertinent redox processes.

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