Modeling the repair of DNA strand breaks caused by γ-radiation in a minichromosome

Abstract

The objective of the studies described here was the development of a mathematical model which would fit experimental data for the repair of single and double strand breaks induced in DNA in living cells by exposure to ionizing radiation, and which would allow to better understand the processes of DNA repair. DNA breaks are believed to play the major role in radiation-induced lethality and formation of chromosome deletions, and are therefore crucial to the response of cells to radiotherapy. In an initial model which we reported on the basis of data for the repair of Epstein-Barr minichromosomes in irradiated Raji cells, we assumed that DNA breaks are induced only at the moment of irradiation and are later removed by repair systems. This work gives a development of that mathematical model which fits the experimental results more precisely and suggests strongly that DNA breaks are generated not only by direct irradiation but also later, probably by systems engaged in repair of oxidative damage.

Adjoint sensitivity analysis of a tumor growth model and its application to spatiotemporal radiotherapy optimization

“…In this work we use adjoint sensitivity analysis, which is a sensitivity method that utilizes the adjoint system constructed based on the analyzed model and simulated backward in time. Adjoint sensitivity analysis, in a special structural form, is especially useful for models described by block diagrams and was originally developed for neural networks [2] and afterwards was used for different models described by ordinary differential equations [3,4,8,9], systems with delays [5] and agestructured models [7]. Adjoint sensitivity analysis is especially useful in analyzing MISO (Multiple-Input Single-Output) systems due to the much lower computational complexity when compared to forward sensitivity analysis.…”

Time-dependent synergy for multi-agent anticancer therapy

“…Sensitivity analysis can be viewed as study of how the change of system’s input affects the change of particular system’s output. This kind of analysis has been used in our previous works to study the behaviour of complex biomedical models [5], parameter estimation process of mathematical models described by various type of differential equations [6–9], or during control optimization tasks [10, 11].…”

Spatiotemporal sensitivity of systems modeled by cellular automata

“…For example, adjoint sensitivity analysis is useful in a parameter estimation process where the analyzed system has many inputs (parameters) and usually one scalar output describing the system (objective function). In a previous study, this method is used to estimate parameters of various types of mathematical models. In the present work, structural adjoint sensitivity analysis is used to compute the spatiotemporal gradient of the objective function with respect to the input signal which affects the system of a 1D cellular automaton with a continuous state.…”