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A nonlinear model consisting of a system of coupled ordinary differential equations (ODE), describing a biological process linked with cancer development, is linearized using Taylor series and tested against different magnitudes of input perturbations, in order to investigate the extent to which the linearization is accurate. The canonical wingless/integrated (WNT) signaling pathway is considered. The linearization procedure is described, and special considerations for linearization validity are analyzed. The analytical properties of nonlinear and linearized systems are studied, including aspects such as existence of steady state and initial value sensitivity. Linearization is a useful tool for speeding up drug response computations or for providing analytical answers to problems such as required drug concentrations. A Monte Carlo-based error testing workflow is employed to study the errors introduced by the linearization for different input conditions and parameter vectors. The deviations between the nonlinear and the linearized system were found to increase in a polynomial fashion w.r.t. the magnitude of tested perturbations. The linearized system closely followed the original one for perturbations of magnitude within 10% of the base input vector which yielded the state-space fixed point used for the linearization.

The goals of this paper are: (a) to investigate adaptive and fractional-order adaptive control algorithms for an automatic anesthesia process, using a closed-loop system, and (b) to develop an easy-to-use tool for MATLAB/Simulink to facilitate simulations for users with less knowledge about anesthesia and adaptive control. A model reference adaptive control structure was chosen for the entire system. First of all, to control the patient’s state during the surgery process, the patient mathematical model is useful, or even required for simulation studies. The pharmacokinetic/pharmacodynamics (PK/PD) model was determined using MATLAB’s SimBiology tool, starting from a previously available block diagram, and validated through simulation. Then, to achieve the desired control performances, two controllers are designed: a PI adaptive controller and a PIλ (PI-fractional) adaptive controller, using the MIT algorithm. The time response during anesthetic drug infusion for each patient can be plotted with the AnesthesiaGUIDE tool, which is also designed in MATLAB/Simulink. The tool was tested on data from 12 patients, subjected to general anesthesia, with successful results. Through this tool, the article provides a good opportunity for any user to experience with adaptive control for the anesthesia process.

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