Cell-extracellular matrix interaction and the mechanical properties of cell nucleus have been demonstrated to play a fundamental role in cell movement across fibre networks and micro-channels and then in the spread of cancer metastases. The lectures will be aimed at presenting several mathematical models dealing with such a problem, starting from modelling cell adhesion mechanics to the inclusion of influence of nucleus stiffness in the motion of cells, through continuum mechanics, kinetic models and individual cell-based models.[-]

This minicourse aims at providing tentative explanations of some specific phenomena observed in the motion of crowds, or more generally collections of living entities. The first lecture shall focus on the so-called Stop and Go Waves, which sometimes spontaneously emerge and persist in crowds in motion. We shall present a general class of dynamical systems which are likely to exhibit this type of instabilities, and emphasize the critical role of two basic ingredients: the asymmetry of interactions, and any sort of delay in the transmission of information through the network of entities. The second lecture will address the Capacity Drop Phenomenon (decrease of the flux though a bottleneck when the upstream density becomes too high), and the more paradoxical Faster is Slower Effect (in some regimes, attempts to go quicker may slow down the overall process). We shall in particular detail how an accurate description of the relative position of entities (at the microscopic level) is crucial to recover and understand those effects.[-]

Emergence is a process by which coherent structures arise through interactions among elementary entities without being directly encoded in these interactions. In this course, we will address some of the key questions of emergence such as the deciphering of the hidden relation between individual behavior and emergent structures. We will start with presenting biologically relevant examples of microscopic individual-based models (IBM). Then, we will develop a systematic coarse-graining approach and derive corresponding coarse-grained models (CGM) using mathematical kinetic theory as the key methodology. We will highlight that novel kinetic theory concepts need to be developed as new mathematical problems arise with emergent systems such as the lack of conservations, the build-up of correlations, or the presence of phase transitions (or bifurcations). Our goal is to show how kinetic theory can be used to provide better understanding of emergence phenomena taking place in a wide variety of biological contexts.[-]

Irreversible electroporation (IRE) is the sole physical ablative technology inducing tumorous cell death by process unrelated to thermal effect. This characteristic makes the technique suitable for the treatment of subtypes of liver tumors especially hepatocellular carcinoma (HCC) located next to critical structures leading to contraindications to thermal ablation like radiofrequency, microwave or cryotherapy. However, while IRE appears safe in such assumed challenging cases for thermal techniques, several issues remain to be addressed to make its use easier and more effective in clinical practice. First of all, tissue changes induced by IRE must be assessed keeping in mind that conversely to thermal techniques its efficacy is not limited to observable coagulative necrotic component of treatment zone. In addition, IRE which is multibipolar ablative technology requires meticulous demanding electrodes positioning to ensure proper magnitude of electric fields between each dipole. Finally, numerical simulations of IRE are mandatory to ease the setting of electrical pulses parameters to improve predictability of treatment in each individual case. In this setting of continue efforts to improve practicability of IRE the technique is routinely used in our institution since several years for the treatment of patients bearing early and locally advanced HCC not amenable to resection or thermal ablation. All along our experience with IRE, imaging appeared as a key point for addressing the specific issues listed above. For the 58 first patients 92% of complete ablation were achieved while the one-year local tumor progression free survival was 70% (95% CI: 56%, 81%). Indeed, despite the need of improvements IRE appears right now as a unique opportunity to achieve complete sustained local tumor control for patient bearing early or locally advanced HCC not amenable to other curative treatments.[-]

The question of using the available measurements to retrieve mathematical models characteristics (parameters, boundary conditions, initial conditions) is a key aspect of the modeling objective in biology or medicine. In a stochastic/statistical framework this question is seen as an estimation problems. From a deterministic point of view, we classical talk about inverse problems as we recover classical model inputs from outputs. When considering evolution problems,this question falls in the realm of data assimilation that can be seen from a deterministic of statistical point of view. Our objective in this course is to introduce the mathematical principles and numerical aspects behind data assimilation strategies with an emphasis on the deterministic formalism allowing to understand why data assimilation is a specific inverse problem. Our presentation will include considerations on finite dimensional problems but also on infinite dimensional problems such as the ones arising from PDE models. And we will illustrate the course with numerous examples coming from cardiovascular applications and biology.[-]