We propose a non-intrusive reduced-order modeling method based on the notion of space-timeparameter proper orthogonal decomposition for approximating the solution of non-linear parametrized time-dependent partial differential equations. A two-level proper orthogonal decomposition method is introduced for constructing spatial and temporal basis functions with special properties such that the reduced-order model satisfies the boundary and initial conditions by construction. A radial basis function approximation method is used to estimate the undetermined coefficients in the reduced-order model without resorting to Galerkin projection. This nonintrusive approach enables the application of our approach to general problems with complicated nonlinearity terms. Numerical studies are presented for the parametrized Burgers' equation and a parametrized convection-reaction-diffusion problem. We demonstrate that our approach leads to reduced-order models that accurately capture the behavior of the field variables as a function of the spatial coordinates, the parameter vector and time.

SUMMARYWe 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 lossof-function b-catenin mutants in the melanocyte lineage. We found that any alteration of b-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 b-catenin.

SUMMARYThis paper presents a methodology for constructing low-order surrogate models of finite element/finite volume discrete solutions of parameterized steady-state partial differential equations. The construction of proper orthogonal decomposition modes in both physical space and parameter space allows us to represent high-dimensional discrete solutions using only a few coefficients. An incremental greedy approach is developed for efficiently tackling problems with high-dimensional parameter spaces. For numerical experiments and validation, several non-linear steady-state convection-diffusion-reaction problems are considered: first in one spatial dimension with two parameters, and then in two spatial dimensions with two and five parameters. In the two-dimensional spatial case with two parameters, it is shown that a 7×7 coefficient matrix is sufficient to accurately reproduce the expected solution, while in the five parameters problem, a 13×6 coefficient matrix is shown to reproduce the solution with sufficient accuracy. The proposed methodology is expected to find applications to parameter variation studies, uncertainty analysis, inverse problems and optimal design.