Biological Systems: Experimentation, Modeling, Control

Understanding the role of the tumor vasculature in the transport of drugs to solid cancer tumors

Authors: Nilmini S. Wijeratne and Karlene A. Hoo*
* Department of Chemical Engineering, Texas Tech University

ABSTRACT

It is well known that the tumor vasculature imposes barriers on transport of drugs to the tumor. In this work a general computational model is developed that describes the mechanisms of drug transport to a solid tumor with an emphasis on modeling the vasculature using solute transport concepts. The effect of the vasculature on transport efficiency is studied using a parametric analysis of some of the transport and biological parameters. It was found that increases in the capillary hydrostatic pressure, diffusive permeability coefficient, and hydraulic conductivity all result in a decrease in the tumor size. Similarly, decreases in the interstitium hydrostatic pressure and filtration constant result in a decrease in tumor size. The dependence of the change in the tumor size to changes in these parameters is nonlinear. These results demonstrate the potential of the integrated computational model of the tumor and its vasculature to estimate the efficacy of a particular treatment process. A case study also is presented to demonstrate the model's flexibility to accommodate a two-cell glioma population.

 

Publication Information: accepted to Journal of Cell Proliferation

Corresponding Author: Karlene A. Hoo

 

An Analytical Approach to Identify Fluid Flow Separation and Re-attachment in a Collapsible Channel

Authors: Nilmini S. Wijeratne and Karlene A. Hoo*
* Department of Chemical Engineering, Texas Tech University

ABSTRACT

The performance of a one-dimensional model that describes the dynamic behavior of a collapsible channel is tested for low Reynolds number flow. Systems of this type are of interest because of their similarity to physiological fluid flow in veins and arteries. Criteria to locate the points of flow separation and flow re-attachment under certain fluid flow conditions are introduced and a numerical approach to provide an approximate analytical solution is demonstrated.

 

Publication Information: Computers and Chemical Engineering, Dec. 2006.

Corresponding Author: Karlene A. Hoo

 

Experimental Studies of the Effects of Abnormal Venous Valves on Fluid Flow

Authors: C. D. Buescher, B. Nachiappan, J. Brumbaugh, H.F. Janssen, and Karlene A. Hoo*
* Department of Chemical Engineering, Texas Tech University

ABSTRACT

The effects of variations in the venous valve anatomy are studied experimentally using an artificial system that mimics the bicuspid valves normally found in veins in the lower extremities. The artificial valves are constructed from thin-walled, latex tubing and polyurethane film. The experimental variables in the study are the gap width between the leaflet attachments at the vein wall and the ratio of the sinus depth to vein diameter. The results show that the antegrade mass flow rate is not affected to the same degree when compared to retrograde flow by the various valve configurations examined in this study. The results also indicate that increases in the gap width, which serve to increase the degree of imperfect wall attachment, have less effect on retrograde mass flow rate in valves with deeper sinuses.

 

Publication Information:   Biotechnology Progress, 21, No.3, pp 938-945, 2005.

Corresponding Author: Karlene A. Hoo

 

Global Linearizing Control of Calcium Dynamics in Cardiac Myocytes

Authors: Zhenhua Tian and Karlene A. Hoo*
* Department of Chemical Engineering, Texas Tech University

ABSTRACT

The external control of a physiological system is a challenging task. In this paper, a nonlinear feedback control design is developed and demonstrated on a system that describes calcium (Ca) fluxes that control muscle contraction and relaxation in human cardiac myocytes or the calcium-induced calcium release mechanism. The particular control formulation uses a global feedback linearization method that is based on differential geometric control theory. The model that describes the calcium dynamics includes the kinetics of ryanodinesensitive (RyR) calcium channels that are critical to signal conversion and cell function in cardiac myocytes and Ca balance among the sarcoplasmic reticulum, the cytosol, and the extracellular space (Tang and Othmer (1994) ). Analysis of the full system is presented to show input multiplicities and the slow approach to the equilibrium (non-pathological) values. To achieve the controller formulation, the full system was divided into two subsytems - one for the RyR kinetics, the other for the Ca balance. The control formulation was then developed for the Ca balance subsystem, which in turn controlled the RyR kinetic subsystem. Without this novel division, the system did not lend itself to this type of advanced control. More than one variable may be used to regulate the Ca balance subsytem. Simulated results are presented to compare the closed-loop performance for two different, but natural, choices of the manipulated variables to regulate the total system in the presence of unmeasured disturbances and parameter uncertainty encountered by the system.

Keywords Ryanodine receptors, calcium-induced calcium-release, feedback control

 

Publication Information:   Journal of Control Theory and Applications, 3, No. 4, pp 348-356, 2005.

Corresponding Author: Karlene A. Hoo