A Data-Driven Space-Time-Parameter Reduced-Order Model with Manifold Learning for Coupled Problems: Application to Deformable Capsules Flowing in Microchannels.

An innovative data-driven model-order reduction technique is proposed to model dilute micrometric or nanometric suspensions of microcapsules, i.e., microdrops protected in a thin hyperelastic membrane, which are used in Healthcare as innovative drug vehicles. We consider a microcapsule flowing in a similar-size microfluidic channel and vary systematically the governing parameter, namely the capillary number, ratio of the viscous to elastic forces, and the confinement ratio, ratio of the capsule to tube size. The resulting space-time-parameter problem is solved using two global POD reduced bases, determined in the offline stage for the space and parameter variables, respectively. A suitable low-order spatial reduced basis is then computed in the online stage for any new parameter instance. The time evolution of the capsule dynamics is achieved by identifying the nonlinear low-order manifold of the reduced variables; for that, a point cloud of reduced data is computed and a diffuse approximation method is used. Numerical comparisons between the full-order fluid-structure interaction model and the reduced-order one confirm both accuracy and stability of the reduction technique over the whole admissible parameter domain. We believe that such an approach can be applied to a broad range of coupled problems especially involving quasistatic models of structural mechanics.

Biological and mathematical modeling of melanocyte development.

We aim to evaluate environmental and genetic effects on the expansion/proliferation of committed single cells during embryonic development, using melanoblasts as a paradigm to model this phenomenon. Melanoblasts are a specific type of cell that display extensive cellular proliferation during development. However, the events controlling melanoblast expansion are still poorly understood due to insufficient knowledge concerning their number and distribution in the various skin compartments. We show that melanoblast expansion is tightly controlled both spatially and temporally, with little variation between embryos. We established a mathematical model reflecting the main cellular mechanisms involved in melanoblast expansion, including proliferation and migration from the dermis to epidermis. In association with biological information, the model allows the calculation of doubling times for melanoblasts, revealing that dermal and epidermal melanoblasts have short but different doubling times. Moreover, the number of trunk founder melanoblasts at E8.5 was estimated to be 16, a population impossible to count by classical biological approaches. We also assessed the importance of the genetic background by studying gain- and loss-of-function ß-catenin mutants in the melanocyte lineage. We found that any alteration of ß-catenin activity, whether positive or negative, reduced both dermal and epidermal melanoblast proliferation. Finally, we determined that the pool of dermal melanoblasts remains constant in wild-type and mutant embryos during development, implying that specific control mechanisms associated with cell division ensure half of the cells at each cell division to migrate from the dermis to the epidermis. Modeling melanoblast expansion revealed novel links between cell division, cell localization within the embryo and appropriate feedback control through ß-catenin.

Modeling melanoblast development.

Melanoblasts are a particular type of cell that displays extensive cellular proliferation during development to contribute to the skin. There are only a few melanoblast founders, initially located just dorsal to the neural tube, and they sequentially colonize the dermis, epidermis, and hair follicles. In each compartment, melanoblasts are exposed to a wide variety of developmental cues that regulate their expansion. The colonization of the dermis and epidermis by melanoblasts involves substantial proliferation to generate thousands of cells or more from a few founders within a week of development. This review addresses the cellular and molecular events occurring during melanoblast development. We focus on intrinsic and extrinsic factors that control melanoblast proliferation. We also present a robust mathematical model for estimating the doubling-time of dermal and epidermal melanoblasts for all coat color phenotypes from black to white.

Data-driven kinematics-consistent model order reduction of fluid-structure interaction problems: application to deformable microcapsules in a Stokes flow.

In this paper, we present a generic approach of a dynamical data-driven model order reduction technique for three-dimensional fluid-structure interaction problems. A low-order continuous linear differential system is identified from snapshot solutions of a high-fidelity solver. The reduced order model (ROM) uses different ingredients like proper orthogonal decomposition (POD), dynamic mode decomposition (DMD) and Tikhonov-based robust identification techniques. An interpolation method is used to predict the capsule dynamics for any value of the governing non-dimensional parameters that are not in the training database. Then a dynamical system is built from the predicted solution. Numerical evidence shows the ability of the reduced model to predict the time-evolution of the capsule deformation from its initial state, whatever the parameter values. Accuracy and stability properties of the resulting low-order dynamical system are analysed numerically. The numerical experiments show a very good agreement, measured in terms of modified Hausdorff distance between capsule solutions of the full-order and low-order models both in the case of confined and unconfined flows. This work is a first milestone to move towards real time simulation of fluid-structure problems, which can be extended to non-linear low-order systems to account for strong material and flow non-linearities. It is a valuable innovation tool for rapid design and for the development of innovative devices.

Melanoblast proliferation dynamics during mouse embryonic development. Modeling and validation.

In this paper, we are looking for mathematical modeling of mouse embryonic melanoblast proliferation dynamics, taking into account, the expression level of ß-catenin. This protein plays an important role into the whole signal pathway process. Different assumptions on some unobservable features lead to different candidate models. From real data measured, from biological experiments and from a priori biological knowledge, it was able to validate or invalidate some of the candidate models. Data assimilation and parameter identification allowed us to derive a mathematical model that is in very good agreement with biological data. As a result, the produced model can give tracks for biologists into their biological investigations and experimental evidence. Another interest is the use of this model for robust hidden parameter identification like double times or number of founder melanoblasts.