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    Asymptotic analysis of a tumor growth model with fractional operators
    (Berlin : Weierstraß-Institut für Angewandte Analysis und Stochastik, 2019) Colli, Pierluigi; Gilardi, Gianni; Sprekels, Jürgen
    In this paper, we study a system of three evolutionary operator equations involving fractional powers of selfadjoint, monotone, unbounded, linear operators having compact resolvents. This system constitutes a generalized and relaxed version of a phase field system of Cahn--Hilliard type modelling tumor growth that has originally been proposed in Hawkins-Daarud et al. (Int. J. Numer. Math. Biomed. Eng. 28 (2012), 3--24). The original phase field system and certain relaxed versions thereof have been studied in recent papers co-authored by the present authors and E. Rocca. The model consists of a Cahn--Hilliard equation for the tumor cell fraction φ, coupled to a reaction-diffusion equation for a function S representing the nutrient-rich extracellular water volume fraction. Effects due to fluid motion are neglected. Motivated by the possibility that the diffusional regimes governing the evolution of the different constituents of the model may be of different (e.g., fractional) type, the present authors studied in a recent note a generalization of the systems investigated in the abovementioned works. Under rather general assumptions, well-posedness and regularity results have been shown. In particular, by writing the equation governing the evolution of the chemical potential in the form of a general variational inequality, also singular or nonsmooth contributions of logarithmic or of double obstacle type to the energy density could be admitted. In this note, we perform an asymptotic analysis of the governing system as two (small) relaxation parameters approach zero separately and simultaneously. Corresponding well-posedness and regularity results are established for the respective cases; in particular, we give a detailed discussion which assumptions on the admissible nonlinearities have to be postulated in each of the occurring cases.
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    Well-posedness and regularity for a fractional tumor growth model
    (Berlin : Weierstraß-Institut für Angewandte Analysis und Stochastik, 2019) Colli, Pierluigi; Gilardi, Gianni; Sprekels, Jürgen
    In this paper, we study a system of three evolutionary operator equations involving fractional powers of selfadjoint, monotone, unbounded, linear operators having compact resolvents. This system constitutes a generalization of a phase field system of Cahn--Hilliard type modelling tumor growth that has been proposed in Hawkins-Daarud et al. (Int. J. Numer. Math. Biomed. Eng. 28 (2012), 3--24) and investigated in recent papers co-authored by the present authors and E. Rocca. The model consists of a Cahn--Hilliard equation for the tumor cell fraction φ, coupled to a reaction-diffusion equation for a function S representing the nutrient-rich extracellular water volume fraction. Effects due to fluid motion are neglected. The generalization investigated in this paper is motivated by the possibility that the diffusional regimes governing the evolution of the different constituents of the model may be of different (e.g., fractional) type. Under rather general assumptions, well-posedness and regularity results are shown. In particular, by writing the equation governing the evolution of the chemical potential in the form of a general variational inequality, also singular or nonsmooth constributions of logarithmic or of double obstacle type to the energy density can be admitted.
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    Second-order analysis of an optimal control problem in a phase field tumor growth model with singular potentials and chemotaxis
    (Berlin : Weierstraß-Institut für Angewandte Analysis und Stochastik, 2020) Colli, Pierluigi; Signori, Andrea; Sprekels, Jürgen
    This paper concerns a distributed optimal control problem for a tumor growth model of Cahn--Hilliard type including chemotaxis with possibly singular anpotentials, where the control and state variables are nonlinearly coupled. First, we discuss the weak well-posedness of the system under very general assumptions for the potentials, which may be singular and nonsmooth. Then, we establish the strong well-posedness of the system in a reduced setting, which however admits the logarithmic potential: this analysis will lay the foundation for the study of the corresponding optimal control problem. Concerning the optimization problem, we address the existence of minimizers and establish both first-order necessary and second-order sufficient conditions for optimality. The mathematically challenging second-order analysis is completely performed here, after showing that the solution mapping is twice continuously differentiable between suitable Banach spaces via the implicit function theorem. Then, we completely identify the second-order Fréchet derivative of the control-to-state operator and carry out a thorough and detailed investigation about the related properties.
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    Optimal control problems with sparsity for phase field tumor growth models involving variational inequalities
    (Berlin : Weierstraß-Institut für Angewandte Analysis und Stochastik, 2021) Colli, Pierluigi; Signori, Andrea; Sprekels, Jürgen
    This paper treats a distributed optimal control problem for a tumor growth model of Cahn--Hilliard type including chemotaxis. The evolution of the tumor fraction is governed by a variational inequality corresponding to a double obstacle nonlinearity occurring in the associated potential. In addition, the control and state variables are nonlinearly coupled and, furthermore, the cost functional contains a nondifferentiable term like the $L^1$--norm in order to include sparsity effects which is of utmost relevance, especially time sparsity, in the context of cancer therapies as applying a control to the system reflects in exposing the patient to an intensive medical treatment. To cope with the difficulties originating from the variational inequality in the state system, we employ the so-called ``deep quench approximation'' in which the convex part of the double obstacle potential is approximated by logarithmic functions. For such functions, first-order necessary conditions of optimality can be established by invoking recent results. We use these results to derive corresponding optimality conditions also for the double obstacle case, by deducing a variational inequality in terms of the associated adjoint state variables. The resulting variational inequality can be exploited to also obtain sparsity results for the optimal controls.