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In this paper, we tackle the problem of reconstructing earlier tumour configurations starting from a single spatial measurement at a later time. We describe the tumour evolution through a diffuse interface model coupling a Cahn-Hilliard-type equation for the tumour phase field to a reaction-diffusion equation for a key nutrient proportion, also accounting for chemotaxis effects. We stress that the ability to reconstruct earlier tumour states is crucial for calibrating the model used to predict the tumour dynamics and also to identify the areas where the tumour initially began to develop. However, backward-in-time inverse problems are well-known to be severely ill-posed, even for linear parabolic equations. Moreover, we also face additional challenges due to the complexity of a non-linear fourth-order parabolic system. Nonetheless, we can establish uniqueness by using logarithmic convexity methods under suitable a priori assumptions. To further address the ill-posedness of the inverse problem, we propose a Tikhonov regularisation approach that approximates the solution through a family of constrained minimisation problems. For such problems, we analytically derive the first-order necessary optimality conditions. Finally, we develop a computationally efficient numerical approximation of the optimisation problems by employing standard $C^0$-conforming first-order finite elements. We conduct numerical experiments on several pertinent test cases and observe that the proposed algorithm consistently meets expectations, delivering accurate reconstructions of the original ground truth., Comment: 54 pages

The development of mathematical models of cancer informed by time-resolved measurements has enabled personalised predictions of tumour growth and treatment response. However, frequent cancer monitoring is rare, and many tumours are treated soon after diagnosis with limited data. To improve the predictive capabilities of cancer models, we investigate the problem of recovering earlier tumour states from a single spatial measurement at a later time. Focusing on prostate cancer, we describe tumour dynamics using a phase-field model coupled with two reaction-diffusion equations for a nutrient and the local prostate-specific antigen. We generate synthetic data using a discretisation based on Isogeometric Analysis. Then, building on our previous analytical work (Beretta et al., SIAP (2024)), we propose an iterative reconstruction algorithm based on the Landweber scheme, showing local convergence with quantitative rates and exploring an adaptive step size that leads to faster reconstruction algorithms. Finally, we run simulations demonstrating high-quality reconstructions even with long time horizons and noisy data., Comment: 37 pages

In this paper we investigate the existence of solutions and their weak-strong uniqueness property for a PDE system modelling damage in viscoelastic materials. In fact, we address two solution concepts, weak and strong solutions. For the former, we obtain a global-in-time existence result, but the highly nonlinear character of the system prevents us from proving their uniqueness. For the latter, we prove local-in-time existence. Then, we show that the strong solution, as long as it exists, is unique in the class of weak solutions. This weak-strong uniqueness statement is proved by means of a suitable relative energy inequality.

Partial differential equation (PDE) models for infectious disease have received renewed interest in recent years. Most models of this type extend classical compartmental formulations with additional terms accounting for spatial dynamics, with Fickian diffusion being the most common such term. However, while diffusion may be appropriate for modeling vector-borne diseases, or diseases among plants or wildlife, the spatial propagation of airborne diseases in human populations is heavily dependent on human contact and mobility patterns, which are not necessarily well-described by diffusion. By including an additional chemotaxis-inspired term, in which the infection is propagated along the positive gradient of the susceptible population (from regions of low- to high-density of susceptibles), one may provide a more suitable description of these dynamics. This article introduces and analyzes a mathematical model of infectious disease incorporating a modified chemotaxis-type term. The model is analyzed mathematically and the well-posedness of the resulting PDE system is demonstrated. A series of numerical simulations are provided, demonstrating the ability of the model to naturally capture important phenomena not easily observed in standard diffusion models, including propagation over long spatial distances over short time scales and the emergence of localized infection hotspots

The availability of cancer measurements over time enables the personalised assessment of tumour growth and therapeutic response dynamics. However, many tumours are treated after diagnosis without collecting longitudinal data, and cancer monitoring protocols may include infrequent measurements. To facilitate the estimation of disease dynamics and better guide ensuing clinical decisions, we investigate an inverse problem enabling the reconstruction of earlier tumour states by using a single spatial tumour dataset and a biomathematical model describing disease dynamics. We focus on prostate cancer, since aggressive cases of this disease are usually treated after diagnosis. We describe tumour dynamics with a phase-field model driven by a generic nutrient ruled by reaction-diffusion dynamics. The model is completed with another reaction-diffusion equation for the local production of prostate-specific antigen, which is a key prostate cancer biomarker. We first improve previous well-posedness results by further showing that the solution operator is continuously Fr\'echet differentiable. We then analyse the backward inverse problem concerning the reconstruction of earlier tumour states starting from measurements of the model variables at the final time. Since this problem is severely ill-posed, only very weak conditional stability of logarithmic type can be recovered from the terminal data. However, by restricting the unknowns to a compact subset of a finite-dimensional subspace, we can derive an optimal Lipschitz stability estimate., Comment: 25 pages

In this paper we consider two diffuse interface models for tumor growth coupling a Cahn-Hilliard type equation for the tumor phase parameter to a reaction-diffusion type equation for the nutrient. The models are distinguished by the presence of two different coupling source terms. For such problems, we address the question of the limit, as the diffuse interface parameter tends to zero, from diffuse interface models to sharp interface ones, justifying rigorously what was deduced via formal asymptotics in [20]. The resulting evolutions turn out to be varifold solutions to Mullins-Sekerka type flows for the tumor region suitably coupled with the equation for the nutrient.

We consider the Oberbeck--Boussinesq approximation driven by an inhomogeneous temperature distribution on the boundary of a bounded fluid domain. The relevant boundary conditions are perturbed by a non--local term arising in the incompressible limit of the Navier--Stokes--Fourier system. The long time behaviour of the resulting initial/boundary value problem is investigated.

In this paper we study nonlocal-to-local asymptotics for a tumor-growth model coupling a viscous Cahn-Hilliard equation describing the tumor proportion with a reaction-diffusion equation for the nutrient phase parameter. First, we prove that solutions to the nonlocal Cahn-Hilliard system converge, as the nonlocality parameter tends to zero, to solutions to its local counterpart. Second, we provide first-order optimality conditions for an optimal control problem on the local model, accounting also for chemotaxis, and both for regular or singular potentials, without any additional regularity assumptions on the solution operator. The proof is based on an approximation of the local control problem by means of suitable nonlocal ones, and on proving nonlocal-to-local convergence both for the corresponding dual systems and for the associated first-order optimality conditions.

In this article, we introduce the concept of energy-variational solutions for a large class of systems of nonlinear evolutionary partial differential equations. Under certain convexity assumptions, the existence of such solutions can be shown constructively by an adapted minimizing movement scheme. Weak-strong uniqueness follows by a suitable relative energy inequality. Our main motivation is to apply the general framework to viscoelastic fluid models. Therefore, we give a short overview on different versions of such models and their derivation. The abstract result is applied to two of these viscoelastic fluid models in full detail. In the conclusion, we comment on further applications of the general theory and its possible impact.

In this paper we consider a nonlinear system of PDEs coupling the viscous Cahn-Hilliard-Oono equation with dynamic boundary conditions enjoying a similar structure on the boundary. After proving well-posedness of the corresponding initial boundary value problem, we study an associated optimal control problem related to a tracking-type cost functional, proving first-order necessary conditions of optimality. The controls enter the system in the form of a distributed and a boundary source. We can account for general potentials in the bulk and in the boundary part under the common assumption that the boundary potential is dominant with respect to the bulk one. For example, the regular quartic potential as well as the logarithmic potential can be considered in our analysis.

In this paper we study a non-local Cahn-Hilliard equation with singular single-well potential and degenerate mobility. This results as a particular case of a more general model derived for a binary, saturated, closed and incompressible mixture, composed by a tumor phase and a healthy phase, evolving in a bounded domain. The general system couples a Darcy-type evolution for the average velocity field with a convective reaction-diffusion type evolution for the nutrient concentration and a non-local convective Cahn-Hilliard equation for the tumor phase. The main mathematical difficulties are related to the proof of the separation property for the tumor phase in the Cahn-Hilliard equation: up to our knowledge, such problem is indeed open in the literature. For this reason, in the present contribution we restrict the analytical study to the Cahn-Hilliard equation only. For the non-local Cahn- Hilliard equation with singular single-well potential and degenerate mobility, we study the existence and uniqueness of weak solutions for spatial dimensions $d\leq 3$. After showing existence, we prove the strict separation property in three spatial dimensions, implying the same property also for lower spatial dimensions, which opens the way to the proof of uniqueness of solutions. Finally, we propose a well posed and gradient stable continuous finite element approximation of the model for $d\leq 3$, which preserves the physical properties of the continuos solution and which is computationally efficient, and we show simulation results in two spatial dimensions which prove the consistency of the proposed scheme and which describe the phase ordering dynamics associated to the system.

This paper is concerned with the well-posedness and optimal control problem of a reaction-diffusion system for an epidemic Susceptible-Infected-Recovered-Susceptible (SIRS) mathematical model in which the dynamics develops in a spatially heterogeneous environment. Using as control variables the transmission rates $u_{i}$ and $u_{e}$ of contagion resulting from the contact with both asymptomatic and symptomatic persons, respectively, we optimize the number of exposed and infected individuals at a final time $T$ of the controlled evolution of the system. More precisely, we search for the optimal $u_{i}$ and $u_{e}$ such that the number of infected plus exposed does not exceed at the final time a threshold value $\Lambda$, fixed a priori. We prove here the existence of optimal controls in a proper functional framework and we derive the first-order necessary optimality conditions in terms of the adjoint variables., Comment: Keywords: COVID-19, partial differential equations, reaction-diffusion system, epidemic models, existence of solutions, uniqueness, optimal control

We propose a new Cahn-Hilliard phase field model coupled to incompressible viscoelasticity at large strains, obtained from a diffuse interface mixture model and formulated in the Eulerian configuration. A new kind of diffusive regularization, of Allen-Cahn type, is introduced in the transport equation for the deformation gradient, together with a regularizing interface term depending on the gradient of the deformation gradient in the free energy of the system. We study the global existence of a weak solution for the model. While standard diffusive regularizations of the transport equation for the deformation gradient presented in literature allows the existence study only for simplified cases, i.e. in two space dimensions and for convex elastic free energy densities of Neo-Hookean type which are independent from the phase field variable, the present regularization allows to study more general cases. In particular, we obtain the global existence of a weak solution in three space dimensions and for generic nonlinear elastic energy densities with polynomial growth. Our analysis considers elastic free energy densities which depend on the phase field variable and which can possibly degenerate for some values of the phase field variable. By means of an iterative argument based on elliptic regularity bootstrap steps, we find the maximum allowed polynomial growths of the Cahn-Hilliard potential and the elastic energy density which guarantee the existence of a solution in three space dimensions. We propose two unconditionally energy stable finite element approximations of the model, based on convex splitting ideas and on the use of a scalar auxiliary variable, proving the existence and stability of discrete solutions. We finally report numerical results for different test cases with shape memory alloy type free energy with pure phases characterized by different elastic properties.

We propose a new class of phase field models coupled to viscoelasticity with large deformations, obtained from a diffuse interface mixture model composed by a phase with elastic properties and a liquid phase. The model is formulated in the Eulerian configuration and it is derived by imposing the mass balance for the mixture components and the momentum balance that comes from a generalized form of the principle of virtual powers. The latter considers the presence of a system of microforces and microstresses associated to the microscopic interactions between the mixture's constituents together with a system of macroforces and macrostresses associated to their viscoelastic behavior, taking into account also the friction between the phases. The free energy density of the system is given as the sum of a Cahn-Hilliard term and an elastic polyconvex term, with a coupling between the phase field variable and the elastic deformation gradient in the elastic contribution. General constitutive assumptions complying with a mechanical version of the second law of thermodynamics in isothermal situations are taken. We study the global existence of a weak solution for a simplified and regularized version of the general model, which considers an incompressible elastic free energy of Neo-Hookean type with elastic coefficients depending on the phase field variable. The regularization is properly designed to deal with the coupling between the phase field variable and the elastic deformation gradient in the elastic energy density. The analysis is made both in two and three space dimensions.

This paper is concerned with the well-posedness of a diffusion-reaction system for a Susceptible-Exposed-Infected-Recovered (SEIR) mathematical model. This model is written in terms of four nonlinear partial differential equations with nonlinear diffusions, depending on the total amount of the SEIR populations. The model aims at describing the spatio-temporal spread of the COVID-19 pandemic and is a variation of the one recently introduced, discussed and tested in [A. Viguerie et al, Diffusion-reaction compartmental models formulated in a continuum mechanics framework: application to COVID-19, mathematical analysis, and numerical study, Comput. Mech. 66 (2020) 1131-1152]. Here, we deal with the mathematical analysis of the resulting Cauchy-Neumann problem: the existence of solutions is proved in a rather general setting and a suitable time discretization procedure is employed. It is worth mentioning that the uniform boundedness of the discrete solution is shown by carefully exploiting the structure of the system. Uniform estimates and passage to the limit with respect to the time step allow to complete the existence proof. Then, two uniqueness theorems are offered, one in the case of a constant diffusion coefficient and the other for more regular data, in combination with a regularity result for the solutions., Comment: Key words: COVID-19, compartmental model, partial differential equations, diffusion-reaction system, initial-boundary value problem, existence of solutions, uniqueness

We propose a new type of diffuse interface model describing the evolution of a tumor mass under the effects of a chemical substance (e.g., a nutrient or a drug). The process is described by utilizing the variables $\varphi$, an order parameter representing the local proportion of tumor cells, and $\sigma$, representing the concentration of the chemical. The order parameter $\varphi$ is assumed to satisfy a suitable form of the Cahn-Hilliard equation with mass source and logarithmic potential of Flory-Huggins type (or generalizations of it). The chemical concentration $\sigma$ satisfies a reaction-diffusion equation where the cross-diffusion term has the same expression as in the celebrated Keller-Segel model. In this respect, the model we propose represents a new coupling between the Cahn-Hilliard equation and a subsystem of the Keller-Segel model. We believe that, compared to other models, this choice is more effective in capturing the chemotactic effects that may occur in tumor growth dynamics (chemically induced tumor evolution and consumption of nutrient/drug by tumor cells). Note that, in order to prevent finite time blowup of $\sigma$, we assume a chemical source term of logistic type. Our main mathematical result is devoted to proving existence of weak solutions in a rather general setting that covers both the two- and three- dimensional cases. Under more restrictive assumptions on coefficients and data, and in some cases on the spatial dimension, we prove various regularity results. Finally, in a proper class of smooth solutions we show uniqueness and continuous dependence on the initial data in a number of significant cases., Comment: 38 pages

In this paper, we deal with the inverse problem of the shape reconstruction of cavities and inclusions embedded in a linear elastic isotropic medium from boundary displacement's measurements. For, we consider a constrained minimization problem involving a boundary quadratic misfit functional with a regularization term that penalizes the perimeter of the cavity or inclusion to be identified. Then using a phase-field approach we derive a robust algorithm for the reconstruction of elastic inclusions and of cavities modeled as inclusions with a very small elasticity tensor.

The paper treats the problem of optimal distributed control of a Cahn-Hilliard-Oono system in $\mathbb{R}^d$, $1\leq d\leq 3$, with the control located in the mass term and admitting general potentials that include both the case of a regular potential and the case of some singular potential. The first part of the paper is concerned with the dependence of the phase variable on the control variable. In the case of a logarithmic potential, we need to prove an ad hoc strict separation property, and for this reason we have to restrict ourselves to the case $d = 2$. In the rest of the work, we study the necessary first-order optimality conditions, which are proved under suitable compatibility conditions on the initial datum of the phase variable and the time derivative of the control, at least in case of potentials having unbounded domain. PLEASE NOTE: A revised version of this paper has been published in Discrete Contin. Dyn. Syst. Ser. S 15 (2022), 2135-2172: the authors point out that both the published version and the arXiv preprint contain a trivial mistake in formula (2.21), which leads to suitable changes in the assumption (2.10) and in some occurrences of it. Namely, (2.21) and (2.10) become $ \bar \varphi(t) = \bar \varphi_0 e^{-t} + \int_0^t e^{-(t-s)} \bar u(s) \, ds$ for every $t\in[0,T]$, and $-M - (\bar\varphi_0)^- , M + (\bar\varphi_0)^+$ belong to the interior of $D(\beta)$, respectively. The formula just after (2.21) becomes $-M - (\bar\varphi_0)^- \leq \bar \varphi(t) \leq M + (\bar\varphi_0)^+$ and a similar change must be done in (4.20). The first line of (2.24) is now implied by the new (2.21). Next, (2.39) becomes $-(M+ R) - (\bar\varphi_0)^- , (M+ R) + (\bar\varphi_0)^+$ belong to the interior of $D(\beta)$. Similar changes must be done in the interval written just two lines before (4.18) and in (4.18) itself., Comment: Key words: Cahn-Hilliard equation, logarithmic potential, regular potential, optimal control problem, strict separation property, necessary optimality conditions

We propose a diffuse interface model to describe tumor as a multicomponent deformable porous medium. We include mechanical effects in the model by coupling the mass balance equations for the tumor species and the nutrient dynamics to a mechanical equilibrium equation with phase-dependent elasticity coefficients. The resulting PDE system couples two Cahn--Hilliard type equations for the tumor phase and the healthy phase with a PDE linking the evolution of the interstitial fluid to the pressure of the system, a reaction-diffusion type equation for the nutrient proportion, and a quasistatic momentum balance. We prove here that the corresponding initial-boundary value problem has a solution in appropriate function spaces.

We propose a variational principle combining a phase-field functional for structural topology optimization with a mixed (three-field) Hu-Washizu functional, then including directly in the formulation equilibrium, constitutive, and compatibility equations. The resulting mixed variational functional is then specialized to derive a classical topology optimization formulation (where the amount of material to be distributed is an \emph{a priori} assigned quantity acting as a global constraint for the problem) as well as a novel topology optimization formulation (where the amount of material to be distributed is minimized, hence with no pre imposed constraint for the problem). Both formulations are numerically solved by implementing a mixed finite element scheme, with the second approach avoiding the introduction of a global constraint, hence respecting the convenient local nature of the finite element discretization. Furthermore, within the proposed approach it is possible to obtain guidelines for settings proper values of phase-field-related simulation parameters and, thanks to the combined phase-field and Hu-Washizu rationale, a monolithic algorithm solution scheme can be easily adopted. An insightful and extensive numerical investigation results in a detailed convergence study and a discussion on the obtained final designs. The numerical results clearly highlight differences between the two formulations as well as advantages related to the monolithic solution strategy; numerical investigations address both two-dimensional and three-dimensional applications., Comment: 35 pages, 14 figures

We consider a phase-field model of prostate cancer growth with chemotherapy and antiangiogenic therapy effects which is introduced in [2]. It is comprised of phase-field equation to describe tumor growth, which is coupled to a reaction-diffusion type equation for generic nutrient for the tumor. An additional equation couples the concentration of prostate-specific antigen (PSA) in the prostatic tissue and it obeys a linear reaction-diffusion equation. The system completes with homogeneous Dirichlet boundary conditions for the tumor variable and Neuman boundary condition for the nutrient and the concentration of PSA. Here we investigate the long time dynamics of the model. We first prove that the initial-boundary value problem generates a strongly continuous semigroup on a suitable phase space that admits the global attractor in a proper phase space. Moreover, we also discuss the convergence of a solution to a single stationary state and obtain a convergence rate estimate under some conditions on the coefficients., Comment: 15 Pages

We study a diffuse interface model describing the evolution of the flow of a binary fluid in a Hele-Shaw cell. The model consists of a Cahn-Hilliard-Darcy (CHD) type system with transport and mass source. A relevant physical application is related to tumor growth dynamics, which in particular justifies the occurrence of a mass inflow. We study the initial-boundary value problem for this model and prove global existence and uniqueness of strong solutions in two space dimensions as well as local existence in three space dimensions.

We introduce the problem of parameter identification for a coupled nonlocal Cahn-Hilliard-reaction-diffusion PDE system stemming from a recently introduced tumor growth model. The inverse problem of identifying relevant parameters is studied here by relying on techniques from optimal control theory of PDE systems. The parameters to be identified play the role of controls, and a suitable cost functional of tracking-type is introduced to account for the discrepancy between some a priori knowledge of the parameters and the controls themselves. The analysis is carried out for several classes of models, each one depending on a specific relaxation (of parabolic or viscous type) performed on the original system. First-order necessary optimality conditions are obtained on the fully relaxed system, in both the two and three-dimensional case. Then, the optimal control problem on the non-relaxed models is tackled by means of asymptotic arguments, by showing convergence of the respective adjoint systems and the minimization problems as each one of the relaxing coefficients vanishes. This allows obtaining the desired necessary optimality conditions, hence to solve the parameter identification problem, for the original PDE system in case of physically relevant double-well potentials., Comment: 39 pages

Prostate cancer can be lethal in advanced stages, for which chemotherapy may become the only viable therapeutic option. While there is no clear clinical management strategy fitting all patients, cytotoxic chemotherapy with docetaxel is currently regarded as the gold standard. However, tumors may regain activity after treatment conclusion and become resistant to docetaxel. This situation calls for new delivery strategies and drug compounds enabling an improved therapeutic outcome. Combination of docetaxel with antiangiogenic therapy has been considered a promising strategy. Bevacizumab is the most common antiangiogenic drug, but clinical studies have not revealed a clear benefit from its combination with docetaxel. Here, we capitalize on our prior work on mathematical modeling of prostate cancer growth subjected to combined cytotoxic and antiangiogenic therapies, and propose an optimal control framework to robustly compute the drug-independent cytotoxic and antiangiogenic effects enabling an optimal therapeutic control of tumor dynamics. We describe the formulation of the optimal control problem, for which we prove the existence of at least a solution and determine the necessary first order optimality conditions. We then present numerical algorithms based on isogeometric analysis to run a preliminary simulation study over a single cycle of combined therapy. Our results suggest that only cytotoxic chemotherapy is required to optimize therapeutic performance and we show that our framework can produce superior solutions to combined therapy with docetaxel and bevacizumab. We also illustrate how the optimal drug-na\"{i}ve cytotoxic effects computed in these simulations may be successfully leveraged to guide drug production and delivery strategies by running a nonlinear least-square fit of protocols involving docetaxel and a new design drug.

We study a stochastic phase-field model for tumor growth dynamics coupling a stochastic Cahn-Hilliard equation for the tumor phase parameter with a stochastic reaction-diffusion equation governing the nutrient proportion. We prove strong well-posedness of the system in a general framework through monotonicity and stochastic compactness arguments. We introduce then suitable controls representing the concentration of cytotoxic drugs administered in medical treatment and we analyze a related optimal control problem. We derive existence of an optimal strategy and deduce first-order necessary optimality conditions by studying the corresponding linearized system and the backward adjoint system., Comment: 39 pages

In this paper we prove the existence of weak solutions for a thermodynamically consistent phase-field model introduced in [26] in two and three dimensions of space. We use a notion of solution inspired by [18], where the pointwise internal energy balance is replaced by the total energy inequality complemented with a weak form of the entropy inequality. Moreover, we prove existence of local-in-time strong solutions and, finally, we show weak-strong uniqueness of solutions, meaning that every weak solution coincides with a local strong solution emanating from the same initial data, as long as the latter exists.

Cytotoxic chemotherapy is a common treatment for advanced prostate cancer. These tumors are also known to rely on angiogenesis, i.e., the growth of local microvasculature via chemical signaling produced by the tumor. Thus, several clinical studies have been investigating antiangiogenic therapy for advanced prostate cancer, either as monotherapy or combined with standard cytotoxic protocols. However, the complex genetic alterations promoting prostate cancer growth complicate the selection of the best chemotherapeutic approach for each patient's tumor. Here, we present a mathematical model of prostate cancer growth and chemotherapy that may enable physicians to test and design personalized chemotherapeutic protocols in silico. We use the phase-field method to describe tumor growth, which we assume to be driven by a generic nutrient following reaction-diffusion dynamics. Tumor proliferation and apoptosis (i.e., programmed cell death) can be parameterized with experimentally-determined values. Cytotoxic chemotherapy is included as a term downregulating tumor net proliferation, while antiangiogenic therapy is modeled as a reduction in intratumoral nutrient supply. Another equation couples the tumor phase field with the production of prostate-specific antigen, which is an extensively used prostate cancer biomarker. We prove the well-posedness of our model and we run a series of representative simulations using an isogeometric method to explore untreated tumor growth as well as the effects of cytotoxic chemotherapy and antiangiogenic therapy, both alone and combined. Our simulations show that our model captures the growth morphologies of prostate cancer as well as common outcomes of cytotoxic and antiangiogenic mono and combined therapy. Our model also reproduces the usual temporal trends in tumor volume and prostate-specific antigen evolution observed in previous studies.

In this paper a phase-field approach for structural topology optimization for a 3D-printing process which includes stress constraint and potentially multiple materials or multiscales is analyzed. First order necessary optimality conditions are rigorously derived and a numerical algorithm which implements the method is presented. A sensitivity study with respect to some parameters is conducted for a two-dimensional cantilever beam problem. Finally, a possible workflow to obtain a 3D-printed object from the numerical solutions is described and the final structure is printed using a fused deposition modeling (FDM) 3D printer.

We investigate the long-time dynamics and optimal control problem of a diffuse interface model that describes the growth of a tumor in presence of a nutrient and surrounded by host tissues. The state system consists of a Cahn-Hilliard type equation for the tumor cell fraction and a reaction-diffusion equation for the nutrient. The possible medication that serves to eliminate tumor cells is in terms of drugs and is introduced into the system through the nutrient. In this setting, the control variable acts as an external source in the nutrient equation. First, we consider the problem of `long-time treatment' under a suitable given source and prove the convergence of any global solution to a single equilibrium as $t\to+\infty$. Then we consider the `finite-time treatment' of a tumor, which corresponds to an optimal control problem. Here we also allow the objective cost functional to depend on a free time variable, which represents the unknown treatment time to be optimized. We prove the existence of an optimal control and obtain first order necessary optimality conditions for both the drug concentration and the treatment time. One of the main aim of the control problem is to realize in the best possible way a desired final distribution of the tumor cells, which is expressed by the target function $\phi_\Omega$. By establishing the Lyapunov stability of certain equilibria of the state system (without external source), we see that $\phi_{\Omega}$ can be taken as a stable configuration, so that the tumor will not grow again once the finite-time treatment is completed.

In the present work we introduce a novel graded-material design based on phase-field and topology optimization. The main novelty of this work comes from the introduction of an additional phase-field variable in the classical single-material phase-field topology optimization algorithm. This new variable is used to grade the material properties in a continuous fashion. Two different numerical examples are discussed, in both of them we perform sensitivity studies to asses the effects of different model parameters onto the resulting structure. From the presented results we can observe that the proposed algorithm adds additional freedom in the design, exploiting the higher flexibility coming from additive manufacturing technology.

We consider the problem of the long time dynamics for a diffuse interface model for tumor growth. The model describes the growth of a tumor surrounded by host tissues in the presence of a nutrient and consists in a Cahn-Hilliard-type equation for the tumor phase coupled with a reaction-diffusion equation for the nutrient concentration. We prove that, under physically motivated assumptions on parameters and data, the corresponding initial-boundary value problem generates a dissipative dynamical system that admits the global attractor in a proper phase space., Comment: 19 pages

We consider a model describing the evolution of a tumor inside a host tissue in terms of the parameters $\varphi_p$, $\varphi_d$ (proliferating and dead cells, respectively), $u$ (cell velocity) and $n$ (nutrient concentration). The variables $\varphi_p$, $\varphi_d$ satisfy a Cahn-Hilliard type system with nonzero forcing term (implying that their spatial means are not conserved in time), whereas $u$ obeys a form of the Darcy law and $n$ satisfies a quasistatic diffusion equation. The main novelty of the present work stands in the fact that we are able to consider a configuration potential of singular type implying that the concentration vector $(\varphi_p,\varphi_d)$ is constrained to remain in the range of physically admissible values. On the other hand, in view of the presence of nonzero forcing terms, this choice gives rise to a number of mathematical difficulties, especially related to the control of the mean values of $\varphi_p$ and $\varphi_d$. For the resulting mathematical problem, by imposing suitable initial-boundary conditions, our main result concerns the existence of weak solutions in a proper regularity class., Comment: 41 pages

In the present contribution we study the sliding mode control (SMC) problem for a diffuse interface tumor growth model coupling a viscous Cahn-Hilliard type equation for the phase variable with a reaction-diffusion equation for the nutrient. First, we prove the well-posedness and some regularity results for the state system modified by the state-feedback control law. Then, we show that the chosen SMC law forces the system to reach within finite time the sliding manifold (that we chose in order that the tumor phase remains constant in time). The feedback control law is added in the Cahn-Hilliard type equation and leads the phase onto a prescribed target $\phi^*$ in finite time., Comment: Key words: sliding mode control, Cahn-Hilliard system, reaction-diffusion equation, tumor growth, nonlinear boundary value problem, state-feedback control law

We present here a model for instantaneous collisions in a solid made of shape memory alloys (SMA) by means of a predictive theory which is based on the introduction not only of macroscopic velocities and temperature, but also of microscopic velocities responsible of the austenite-martensites phase changes. Assuming time discontinuities for velocities, volume fractions and temperature, and applying the principles of thermodynamics for non-smooth evolutions together with constitutive laws typical of SMA, we end up with a system of nonlinearly coupled elliptic equations for which we prove an existence and uniqueness result in the 2 and 3 D cases. Finally, we also present numerical results for a SMA 2D solid subject to an external percussion by an hammer stroke.

In the present paper, a continuum model is introduced for fluid flow in a deformable porous medium, where the fluid may undergo phase transitions. Typically, such problems arise in modeling liquid-solid phase transformations in groundwater flows. The system of equations is derived here from the conservation principles for mass, momentum, and energy and from the Clausius-Duhem inequality for entropy. It couples the evolution of the displacement in the matrix material, of the capillary pressure, of the absolute temperature, and of the phase fraction. Mathematical results are proved under the additional hypothesis that inertia effects and shear stresses can be neglected. For the resulting highly nonlinear system of two PDEs, one ODE and one ordinary differential inclusion with natural initial and boundary conditions, existence of global in time solutions is proved by means of cut-off techniques and suitable Moser-type estimates.

We study a non-local variant of a diffuse interface model proposed by Hawkins--Darrud et al. (2012) for tumour growth in the presence of a chemical species acting as nutrient. The system consists of a Cahn--Hilliard equation coupled to a reaction-diffusion equation. For non-degenerate mobilities and smooth potentials, we derive well-posedness results, which are the non-local analogue of those obtained in Frigeri et al. (European J. Appl. Math. 2015). Furthermore, we establish existence of weak solutions for the case of degenerate mobilities and singular potentials, which serves to confine the order parameter to its physically relevant interval. Due to the non-local nature of the equations, under additional assumptions continuous dependence on initial data can also be shown., Comment: 28 pages

We consider an optimal control problem for a diffuse interface model of tumor growth. The state equations couples a Cahn-Hilliard equation and a reaction-diffusion equation, which models the growth of a tumor in the presence of a nutrient and surrounded by host tissue. The introduction of cytotoxic drugs into the system serves to eliminate the tumor cells and in this setting the concentration of the cytotoxic drugs will act as the control variable. Furthermore, we allow the objective functional to depend on a free time variable, which represents the unknown treatment time to be optimized. As a result, we obtain first order necessary optimality conditions for both the cytotoxic concentration and the treatment time., Comment: 39 pages

In this paper, a distributed optimal control problem is studied for a diffuse interface model of tumor growth which was proposed in [A. Hawkins-Daruud, K.G. van der Zee, J.T. Oden, Numerical simulation of a thermodynamically consistent four-species tumor growth model, Int. J. Numer. Math. Biomed. Engng. 28 (2011), 3-24]. The model consists of a Cahn-Hilliard equation for the tumor cell fraction coupled to a reaction-diffusion equation for a variable representing the nutrient-rich extracellular water volume fraction. The distributed control monitors as a right-hand side the reaction-diffusion equation and can be interpreted as a nutrient supply or a medication, while the cost function, which is of standard tracking type, is meant to keep the tumor cell fraction under control during the evolution. We show that the control-to-state operator is Frechet differentiable between appropriate Banach spaces and derive the first-order necessary optimality conditions in terms of a variational inequality involving the adjoint state variables., Comment: A revised version of the paper has been published on Nonlinearity 30 (2017), 2518-2546. Let us point out that in this arXiv:1601.04567 [math.AP] version there is something missing in assumption (H3) at page 6: the first initial value in (H6) must also satisfy a Neumann homogeneous condition at the boundary of the domain

A PDE system consisting of the momentum balance, mass balance, and energy balance equations for displacement, capillary pressure, and temperature as a model for unsaturated fluid flow in a porous viscoelastoplastic solid is shown to admit a solution under appropriate assumptions on the constitutive behavior. The problem involves two hysteresis operators accounting for plastic and capillary hysteresis.

This contribution deals with a class of models combining isotropic damage with plasticity. We are inspired by It has been inspired by a work by Freddi and Royer-Carfagni, including the case where the inelastic part of the strain only evolves in regions where the material is damaged. The evolution both of the damage and of the plastic variable is assumed to be rate-independent. Existence of solutions is established in the abstract energetic framework elaborated by Mielke and coworkers.

We consider a full Navier-Stokes and $Q$-tensor system for incompressible liquid crystal flows of nematic type. In the two dimensional periodic case, we prove the existence and uniqueness of global strong solutions that are uniformly bounded in time. This result is obtained without any smallness assumption on the physical parameter $\xi$ that measures the ratio between tumbling and aligning effects of a shear flow exerting over the liquid crystal directors. Moreover, we show the uniqueness of asymptotic limit for each global strong solution as time goes to infinity and provide an uniform estimate on the convergence rate.

We consider a diffuse interface model for tumor growth recently proposed in [Y. Chen, S.M. Wise, V.B. Shenoy, J.S. Lowengrub, A stable scheme for a nonlinear, multiphase tumor growth model with an elastic membrane, Int. J. Numer. Methods Biomed. Eng., 30 (2014), 726-754]. In this new approach sharp interfaces are replaced by narrow transition layers arising due to adhesive forces among the cell species. Hence, a continuum thermodynamically consistent model is introduced. The resulting PDE system couples four different types of equations: a Cahn-Hilliard type equation for the tumor cells (which include proliferating and dead cells), a Darcy law for the tissue velocity field, whose divergence may be different from 0 and depend on the other variables, a transport equation for the proliferating (viable) tumor cells, and a quasi-static reaction diffusion equation for the nutrient concentration. We establish existence of weak solutions for the PDE system coupled with suitable initial and boundary conditions. In particular, the proliferation function at the boundary is supposed to be nonnegative on the set where the velocity ${\bf u}$ satisfies ${\bf u}\cdot\nu>0$, where $\nu$ is the outer normal to the boundary of the domain. We also study a singular limit as the diffuse interface coefficient tends to zero.

In this paper we introduce a general abstract formulation of a variational thermomechanical model, by means of a unified derivation via a generalization of the principle of virtual powers for all the variables of the system, including the thermal one. In particular, choosing as thermal variable the entropy of the system, and as driving functional the internal energy, we get a gradient flow structure (in a suitable abstract setting) for the whole nonlinear PDE system. We prove a global in time existence of (weak) solutions result for the Cauchy problem associated to the abstract PDE system as well as uniqueness in case of suitable smoothness assumptions on the functionals.

In the present contribution the sliding mode control (SMC) problem for a phase-field model of Caginalp type is considered. First we prove the well-posedness and some regularity results for the phase-field type state systems modified by the state-feedback control laws. Then, we show that the chosen SMC laws force the system to reach within finite time the sliding manifold (that we chose in order that one of the physical variables or a combination of them remains constant in time). We study three different types of feedback control laws: the first one appears in the internal energy balance and forces a linear combination of the temperature and the phase to reach a given (space dependent) value, while the second and third ones are added in the phase relation and lead the phase onto a prescribed target. While the control law is non-local in space for the first two problems, it is local in the third one, i.e., its value at any point and any time just depends on the value of the state., Comment: Key words: phase field system, nonlinear boundary value problems, phase transition, sliding mode control, state-feedback control law

A weak formulation for the so-called "semilinear strongly damped wave equation with constraint" is introduced and a corresponding notion of solution is defined. The main idea in this approach consists in the use of duality techniques in Sobolev-Bochner spaces, aimed at providing a suitable "relaxation" of the constraint term. A global in time existence result is proved under the natural condition that the initial data have finite "physical" energy., Comment: 21 pages

This paper is concerned with a phase field system of Cahn-Hilliard type that is related to a tumor growth model and consists of three equations in terms of the variables order parameter, chemical potential and nutrient concentration. This system has been investigated in the recent contributions arXiv:1401.5943 [math.AP] and arXiv:1501.07057 [math.AP] from the viewpoint of well-posedness, long time behavior and asymptotic convergence as two positive viscosity coefficients tend to zero at the same time. Here, we continue the analysis performed in arXiv:1501.07057 [math.AP] by showing two independent sets of results as just one of the coefficients tends to zero, the other remaining fixed. We prove convergence results, uniqueness of solutions to the two resulting limit problems, and suitable error estimates., Comment: Key words: tumor growth, Cahn-Hilliard system, reaction-diffusion equation, asymptotic analysis, error estimates. arXiv admin note: text overlap with arXiv:1501.07057

In this paper we perform an asymptotic analysis for two different vanishing viscosity coefficients occurring in a phase field system of Cahn-Hilliard type that was recently introduced in order to approximate a tumor growth model. In particular, we extend some recent results obtained in the preprint arXiv:1401.5943, letting the two positive viscosity parameters tend to zero independently from each other and weakening the conditions on the initial data in such a way as to maintain the nonlinearities of the PDE system as general as possible. Finally, under proper growth conditions on the interaction potential, we prove an error estimate leading also to the uniqueness result for the limit system.

We prove existence, uniqueness, regularity and separation properties for a nonlocal Cahn-Hilliard equation with a reaction term. We deal here with the case of logarithmic potential and degenerate mobility as well an uniformly lipschitz in $u$ reaction term $g(x,t,u).$