Dynamic Model of Tumor Growth (1)

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Enzyme kinetics: full model

Model description: 

This is a full polynomial form of the model, given in Enzyme kinetics:

$$\begin{align*} \dot{x}_1 &= -bx_1 + ax_5\\ \dot{x}_2 &= \alpha x_1 - \beta x_2\\ \dot{x}_3 &= \gamma x_2 - \delta x_3\\ \dot{x}_4 &= \sigma x_4 x_6 ( \gamma x_2 - \delta x_3) \\ \dot{x}_5 &= -\sigma x_4 x_5^2 x_6 ( \gamma x_2 - \delta x_3)\\ \dot{x}_6 &= -x_6^2( \gamma x_2 - \delta x_3) \end{align*}$$

with $x_1(0) = 0.3617$, $x_2(0) = 0.9137$, $x_3(0)=1.3934$, $x_4(0) = x_3(0)^{\sigma}$, $x_5(0)=\dfrac{1}{A+x_3(0)^{\sigma}}$, $x_6(0)=\dfrac{1}{x_3(0)}.$

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6

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TitleStructural Identifiability of Systems Biology Models: A Critical Comparison of Methods
Publication TypeJournal Article
Year of Publication2011
AuthorsChis, Oana-Teodora, Banga Julio R., and Balsa-Canto Eva
Secondary AuthorsJaeger, JohannesEditor
JournalPLoS ONE
Volume6
Start Page1
Issue11
Pagination1-16
Date Published10/2011
ISSN1932-6203
AbstractAnalysing the properties of a biological system through in silico experimentation requires a satisfactory mathematical representation of the system including accurate values of the model parameters. Fortunately, modern experimental techniques allow obtaining time-series data of appropriate quality which may then be used to estimate unknown parameters. However, in many cases, a subset of those parameters may not be uniquely estimated, independently of the experimental data available or the numerical techniques used for estimation. This lack of identifiability is related to the structure of the model, i.e. the system dynamics plus the observation function. Despite the interest in knowing a priori whether there is any chance of uniquely estimating all model unknown parameters, the structural identifiability analysis for general non-linear dynamic models is still an open question. There is no method amenable to every model, thus at some point we have to face the selection of one of the possibilities. This work presents a critical comparison of the currently available techniques. To this end, we perform the structural identifiability analysis of a collection of biological models. The results reveal that the generating series approach, in combination with identifiability tableaus, offers the most advantageous compromise among range of applicability, computational complexity and information provided.
DOI10.1371/journal.pone.0027755

Chemical Reactor Model

Model description: 

The following two-dimensional single-input single-output system represents a chemical reactor model

$$\begin{align*} \dot{x}_1 &= u(Ce -x_1) - rx_1 \\ \dot{x}_2 &= rx_1 - ux_2 \\ y &= x_1 - x_2, \end{align*}$$

where coefficients are in $\mathbb{R}$, $x_1$ and $x_2$ denote the reactant and product concentrations, respectively. The input $u$ corresponds to the input flow of reactant, $r$ and $C_e$ denote kinetic and reactor parameters.

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TitleObserver Synthesis for a Class of Bilinear Systems: a Differential Algebraic Approach
Publication TypeConference Paper
Year of Publication1994
AuthorsMartinez-Guerra, R., and De Leon-Morales J.
Conference NameProceedings of the 33rd IEEE Conference on Decision and Control, 1994.
Date Published12/1994
PublisherIEEE
Conference LocationConference Location : Lake Buena Vista, FL
ISBN Number0-7803-1968-0
Accession Number5016344
Keywordsalgebra, bilinear systems, differential equations, observers
AbstractA differential algebraic approach is proposed for the estimation of the state of a class of bilinear systems. An exponential observer is easily constructed for a single output observable bilinear system class (in the observability sense of Diop and Fliess, 1991). An application to a chemical reactor model is given.
DOI10.1109/CDC.1994.411167

Three Degree of Freedom Helicopter Model

Model description: 

We consider the attached image where the VARIO helicopter mounted on an experimental platform is represented. It is important to say that in this particular case the helicopter is in an OGE condition. The effects of the compressed air in take-off and landing are then neglected. The model has the form

$$M(q)\ddot{q}+C(q,\dot{q})\dot{q}+G(q)=Q(u),$$

where $M(q)\in\mathbb{R}^{3\times3}$ is the inertia matrix, $C(q,\dot{q})\in\mathbb{R}^{3\times3}$ is the Coriolis matrix, $G(q)\in\mathbb{R}^3$ is the vector of conservative forces, $Q(u)=\begin{bmatrix}f_z & \tau_z & \tau_\gamma \end{bmatrix}^{\mathrm T}$ is the vector of generalized forces, $q = \begin{bmatrix} z & \phi & \gamma \end{bmatrix}^{\mathrm T}$ is the vector of generalized coordinates and $u=\begin{bmatrix}h_M & h_T \end{bmatrix}^{\mathrm T}$ is the vector of control inputs. Here $f_Z, \tau_Z$ and $\tau_{\gamma}$ are the vertical forces, the yaw torque and the main rotor torque, respectively. The height $z < 0$ upwards, $\phi$ is the yaw angle and $\gamma$ is the main rotor azimuth angle.

$M(q)=\begin{bmatrix} c_0 & 0 & 0 \\ 0 & c_1 + c_2 \cos^2{(c_3\gamma)} & c_4\\ 0 & c_4 & c_5 \end{bmatrix},$

$C(q,\dot{q})=\begin{bmatrix} 0 & 0 & 0\\ 0 & c_6\sin{(2c_3\gamma)}\dot{\gamma} & c_6\sin{(2c_3\gamma)}\dot{\phi} \\ 0 & -c_6\sin{(2c_3\gamma)}\dot{\phi} & 0\end{bmatrix},$

$G(q)=\begin{bmatrix}c_7 \\ 0 \\ 0 \end{bmatrix},$

where $c_i$'s $i = 0, ..., 7$ are the physical constants given in the table below.

The generalized forces vector is given by

$Q(u)=\begin{bmatrix} c_8\dot{\gamma}^2u_1 + c_9\dot{\gamma} + c_{10} \\ c_{11}\dot{\gamma}^2u_2\\ (c_{12}\dot{\gamma}^2 + c_{13})u_1 + c_{14}\dot{\gamma}^2 + c_{15} \end{bmatrix}$

$c_i$ Numerical value
$c_0$ $7.5$ $kg$
$c_1$ $0.4305$ $kg\times m^2$
$c_2$ $3 \times 10^{-4}$ $kg\times m^2$
$c_3$ $-4.143$
$c_4$ $0.108$ $kg\times m^2$
$c_5$ $0.4993$ $kg\times m^2$
$c_6$ $-6.214 \times 10^{-4}$ $kg\times m^2$
$c_7$ $-73.58$ $N$
$c_8$ $3.411$ $kg$
$c_9$ $0.6004$ $kg \times m/s$
$c_{10}$ $3.679$ $N$
$c_{11}$ $-0.1525$ $mg \times m$
$c_{12}$ $12.01$ $kg \times m/s$
$c_{13}$ $1 \times 10^{5}$ $N$
$c_{14}$ $1.206 \times 10^{-4}$ $kg \times m^2$
$c_{15}$ $2.642$ $N$

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TitleNonlinear modelling and control of helicopters
Publication TypeJournal Article
Year of Publication2003
AuthorsVilchis, J.C. Avila, Brogliato B., Dzul A., and Lozano R.
JournalAutomatica
Volume39
Pagination1583-1596
Date Published09/2003
ISSN0005-1098
KeywordsAerodynamics, Helicopter; Drone, Nonlinear control, nonlinear systems, Underactuated
AbstractThis paper presents the development of a nonlinear model and of a nonlinear control strategy for a VARIO scale model helicopter. Our global interest is a 7-DOF (degree-of-freedom) general model to be used for the autonomous forward-flight of helicopter drones. However, in this paper we focus on the particular case of a reduced-order model (3-DOF) representing the scale model helicopter mounted on an experimental platform. Both cases represent underactuated systems ($u \in \mathbb{R}^4$ for the 7-DOF model and $u \in \mathbb{R}^2$ for the 3-DOF model studied in this paper). The proposed nonlinear model possesses quite specific features which make its study an interesting challenge, even in the 3-DOF case. In particular aerodynamical forces result in input signals and matrices which significantly differ from what is usually considered in the literature on mechanical systems control. Numerical results and experiments on a scale model helicopter illustrate the theoretical developments, and robustness with respect to parameter uncertainties is studied.
DOI10.1016/s0005-1098(03)00168-7

Dynamic Model of Tumor Growth (2)

Model description: 

Consider the model from Dynamic Model of Tumor Growth (1). The complete model formulation describes the phenomenology of tumor growth slowdown, as the tumor consumes its available support; stimulatory and inhibitory influences from the tumor cells; inhibition due to administered inhibitors; and the clearance of the administered inhibitor. In the simplified model, the latter effect is not described, only the serum level of the inhibitor to be maintained is represented, so a second-order system is to be analyzed:

$$\begin{align*} \dot{x}_{1} &=-\lambda x_{1}\ln\left(\dfrac{x_{1}}{x_{2}}\right) \\ \dot{x}_2 &= b_x1 - dx_1^{{2}\over{3}}x_2 - ex_2u \\ y&=x_1, \end{align*}$$

where $x_1$ is the tumor volume (mm$^3$), $x_2$ is the vasculature volume (mm$^3$), and $u$ is the serum level of the inhibitor (mg/kg). The last equation represents that tumor volume is the measured output of the system. The characteristics of the parameters for the Lewis lung carcinoma and the mice used in the experiment are: $\lambda = 0.192($day$^{-1})$, $b = 5.85 ($day$^{−1}),$ $d =0.00873 ($day$^{−1}$mm$^{−2}),$ while the parameter characteristic for the inhibitor (endostatin) is: $e = 0.66 ($day$^{−1} ($mg/kg$)^{−1}).$ Attached figure shows the nonlinear behavior of the simplified model.

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2

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Publication details: 

TitleModel-based Angiogenic Inhibition of Tumor Growth using Feedback Linearization
Publication TypeConference Paper
Year of Publication2013
AuthorsSzeles, A., Drexler D.A., Sapi J., Harmati I., and Kovacs L.
Conference NameIEEE 52nd Annual Conference on Decision and Control (CDC), 2013
Date Published12/2013
PublisherIEEE
Conference LocationFirenze
ISBN Number978-1-4673-5714-2
Accession Number14158507
Keywordscancer, feedback, linearisation techniques, medical control systems, nonlinear control systems, patient treatment, time-varying systems, tumours
AbstractIn the last decades beside conventional cancer treatment methods, molecular targeted therapies show prosperous results. These therapies have limited side-effects, and in comparison to chemotherapy, tumorous cells show lower tendency of becoming resistant to the applied antiangiogenic drugs. In clinical research, antiangiogenic therapy is one of the most promising cancer treatment methods. Using a simplified model of the reference dynamical model for tumor growth under angiogenic inhibition from the literature, exact linearization is performed in the paper to handle the nonlinear behavior of the model. Two different control methods are applied on the linearized model: flat control and switching control. Simulations are performed on the nonlinear model to show the characteristics of the therapies carried out using the presented control methods.
DOI10.1109/CDC.2013.6760184

Dynamic Model of Tumor Growth (1)

Model description: 

In 1999, a research was carried out at the Harvard Medical University by Philip Hahnfeldt et al. to investigate experimentally and theoretically the effects of angiogenic inhibitors on tumor growth dynamics. They posed a quantitative theory for tumor growth under angiogenic stimulator/inhibitor control. In their experiments, mice were injected with Lewis lung carcinoma cells. The following equations comprise the entire model formulation:

$$\begin{align*} \dot{x}_1 &=-\lambda_1x_1\ln\left(\frac{x_1}{x_2}\right) \\ \dot{x}_2 &=bx_1-dx_1^{\frac{2}{3}}x_2-ex_2x_3 \\ \dot{x}_3 &=\int_0^tu(t^{\prime})\exp(-\lambda_{3}(t-t^{\prime})){\mathrm d}t^{\prime} \\ y &=x_{1}, \end{align*}$$

where $x_1$is the tumor volume (mm$^3$), $x_2$is the supporting vasculature volume (mm$^3$), $x_3$ is the inhibitor serum level (mg/kg), and $u$ is the inhibitor administration rate (mg/kg/day).

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Publication details: 

TitleModel-based Angiogenic Inhibition of Tumor Growth using Feedback Linearization
Publication TypeConference Paper
Year of Publication2013
AuthorsSzeles, A., Drexler D.A., Sapi J., Harmati I., and Kovacs L.
Conference NameIEEE 52nd Annual Conference on Decision and Control (CDC), 2013
Date Published12/2013
PublisherIEEE
Conference LocationFirenze
ISBN Number978-1-4673-5714-2
Accession Number14158507
Keywordscancer, feedback, linearisation techniques, medical control systems, nonlinear control systems, patient treatment, time-varying systems, tumours
AbstractIn the last decades beside conventional cancer treatment methods, molecular targeted therapies show prosperous results. These therapies have limited side-effects, and in comparison to chemotherapy, tumorous cells show lower tendency of becoming resistant to the applied antiangiogenic drugs. In clinical research, antiangiogenic therapy is one of the most promising cancer treatment methods. Using a simplified model of the reference dynamical model for tumor growth under angiogenic inhibition from the literature, exact linearization is performed in the paper to handle the nonlinear behavior of the model. Two different control methods are applied on the linearized model: flat control and switching control. Simulations are performed on the nonlinear model to show the characteristics of the therapies carried out using the presented control methods.
DOI10.1109/CDC.2013.6760184

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