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Development of human corneal epithelium on organized fibrillated transparent collagen matrices synthesized at high concentration
International audienceSeveral diseases can lead to opacification of cornea requiring transplantation of donor tissue to restore vision. In this context, transparent collagen I fibrillated matrices have been synthesized at 15, 30, 60 and 90 mg/mL. The matrices were evaluated for fibril organizations, transparency, mechanical properties and ability to support corneal epithelial cell culture. The best results were obtained with 90 mg/mL scaffolds. At this concentration, the fibril organization presented some similarities to that found in corneal stroma. Matrices had a mean Young's modulus of 570 kPa and acellular scaffolds had a transparency of 87% in the 380-780 nm wavelength range. Human corneal epithelial cells successfully colonized the surface of the scaffolds and generated an epithelium with characteristics of corneal epithelial cells (i.e. expression of cytokeratin 3 and presence of desmosomes) and maintenance of stemness during culture (i.e. expression of Delta Np63 alpha and formation of holoclones in colony formation assay). Presence of cultured epithelium on the matrices was associated with increased transparency (89%). (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved
DYNAMICO-1.0, an icosahedral hydrostatic dynamical core designed for consistency and versatility
International audienceThe design of the icosahedral dynamical core DY-NAMICO is presented. DYNAMICO solves the multi-layer rotating shallow-water equations, a compressible variant of the same equivalent to a discretization of the hydrostatic primitive equations in a Lagrangian vertical coordinate, and the primitive equations in a hybrid mass-based vertical coordinate. The common Hamiltonian structure of these sets of equations is exploited to formulate energy-conserving spatial discretizations in a unified way. The horizontal mesh is a quasi-uniform icosahedral C-grid obtained by subdivision of a regular icosahedron. Control volumes for mass, tracers and entropy/potential temperature are the hexagonal cells of the Voronoi mesh to avoid the fast numerical modes of the triangular C-grid. The horizontal discretization is that of Ringler et al. (2010), whose discrete quasi-Hamiltonian structure is identified. The prognos-tic variables are arranged vertically on a Lorenz grid with all thermodynamical variables collocated with mass. The vertical discretization is obtained from the three-dimensional Hamiltonian formulation. Tracers are transported using a second-order finite-volume scheme with slope limiting for positivity. Explicit Runge–Kutta time integration is used for dynamics, and forward-in-time integration with horizon-tal/vertical splitting is used for tracers. Most of the model code is common to the three sets of equations solved, making it easier to develop and validate each piece of the model separately. Representative three-dimensional test cases are run and analyzed, showing correctness of the model. The design permits to consider several extensions in the near future, from higher-order transport to more general dynamics, especially deep-atmosphere and non-hydrostatic equations
Ex vivo multiscale quantitation of skin biomechanics in wild-type and genetically-modified mice using multiphoton microscopy
International audienceSoft connective tissues such as skin, tendon or cornea are made of about 90% of extracellular matrix proteins, fibrillar collagens being the major components. Decreased or aberrant collagen synthesis generally results in defective tissue mechanical properties as the classic form of Elhers-Danlos syndrome (cEDS). This connective tissue disorder is caused by mutations in collagen V genes and is mainly characterized by skin hyperextensibility. To investigate the relationship between the microstructure of normal and diseased skins and their macroscopic mechanical properties, we imaged and quantified the microstructure of dermis of ex vivo murine skin biopsies during uniaxial mechanical assay using multiphoton microscopy. We used two genetically-modified mouse lines for collagen V: a mouse model for cEDS harboring a Col5a2 deletion (a.k.a. pN allele) and the transgenic K14-COL5A1 mice which overexpress the human COL5A1 gene in skin. We showed that in normal skin, the collagen fibers continuously align with stretch, generating the observed increase in mechanical stress. Moreover, dermis from both transgenic lines exhibited altered collagen reorganization upon traction, which could be linked to microstructural modifications. These findings show that our multiscale approach provides new crucial information on the biomechanics of dermis that can be extended to all collagen-rich soft tissues
Relaxations convexes et spectrales pour les problèmes de reconstruction de phase, seriation et classement
Optimization is often the computational bottleneck in disciplines such as statistics, biology, physics, finance or economics. Many optimization problems can be directly cast in the well- studied convex optimization framework. For non-convex problems, it is often possible to derive convex or spectral relaxations, i.e., derive approximations schemes using spectral or convex optimization tools. Convex and spectral relaxations usually provide guarantees on the quality of the retrieved solutions, which often transcribes in better performance and robustness in practical applications, compared to naive greedy schemes. In this thesis, we focus on the problems of phase retrieval, seriation and ranking from pairwise comparisons. For each of these combinatorial problems we formulate convex and spectral relaxations that are robust, flexible and scalable.L’optimisation s’avère souvent essentielle dans de nombreuses disciplines: statistiques, biologie, physique, finance ou encore économie. De nombreux problèmes d’optimisation peuvent être directement formulés dans le cadre de l’optimisation convexe, un domaine très bien étudié. Pour les problèmes non convexes, il est souvent possible d’écrire des relaxations convexes ou spectrales, i.e., d’établir des schémas d’approximations utilisant des techniques convexes ou spectrales. Les relaxations convexes et spectrales fournissent en général des garanties sur la qualité des solutions associées. Cela se traduit souvent par de meilleures performances et une plus grande robustesse dans les applications, par rapport à des méthodes gloutonnes naïves. Dans ce manuscript de thèse, nous nous intéressons aux problèmes de reconstruction de phase, de sériation, et de classement à partir de comparaisons par paires. Nous formulons pour chacun de ces problèmes des relaxations convexes ou spectrales à la fois robustes, flexibles, et adaptées à de grands jeux de données
Probing the transversity spin structure of a nucleon in neutrino-production of a charmed meson
6 pages, 2 figures, 6th international conference on Physics Opportunities at an Electron-Ion Collider, POETIC-6, September 7-11 2015, Ecole polytechnique, Palaiseau, FranceInternational audienceIncluding O(m_c) terms in the coefficient functions and/or O(m_D) twist 3 contributions in the heavy meson distribution amplitudes leads to a non-zero transverse amplitude for exclusive neutrino production of a D pseudoscalar charmed meson on an unpolarized target. We work in the framework of the collinear QCD approach where chiral-odd transversity generalized parton distributions (GPDs) factorize from perturbatively calculable coefficient functions
Statistical modelling of wildfire size and intensity: a step toward meteorological forecasting of summer extreme fire risk
International audienceIn this article we investigate the use of statistical methods for wildfire risk assessment in the Mediterranean Basin using three meteorological covariates, the 2 m temperature anomaly, the 10 m wind speed and the January– June rainfall occurrence anomaly. We focus on two remotely sensed characteristic fire variables, the burnt area (BA) and the fire radiative power (FRP), which are good proxies for fire size and intensity respectively. Using the fire data we determine an adequate parametric distribution function which fits best the logarithm of BA and FRP. We reconstruct the conditional density function of both variables with respect to the chosen meteorological covariates. These conditional density functions for the size and intensity of a single event give information on fire risk and can be used for the estimation of conditional probabilities of exceeding certain thresholds. By analysing these probabilities we find two fire risk regimes different from each other at the 90 % confidence level: a " background " summer fire risk regime and an " extreme " additional fire risk regime, which corresponds to higher probability of occurrence of larger fire size or intensity associated with specific weather conditions. Such a statistical approach may be the ground for a future fire risk alert system
Innovation-based sparse estimation of functional connectivity from multivariate autoregressive models
International audienceOne of the main limitations of functional connectivity estimators of brain networks is that they can suffer from statistical reliability when the number of areas is large and the available time series are short. To estimate directed functional connectivity with multivariate autoregressive (MVAR) model on sparse connectivity assumption, we propose a modified Group Lasso procedure with an adapted penalty. Our procedure includes the innovation estimates as explaining variables. This approach is inspired by two criteria that are used to interpret the coefficients of the MVAR model, the Directed Transfer Function (DTF) and the Partial Directed Coherence (PDC). A causality measure can be deduced from the output coefficients which can be understood as a synthesis of PDC and DTF. We demonstrate the potential of our method and compare our results with the standard Group Lasso on simulated data. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only
Spatial Computing in Synthetic Bioware: Creating Bacterial Architectures
International audienceSynthetic biology is an emerging scientific field that promotes the standardized manufacturing of biological components without natural equivalents. Its goal is to create artificial living systems that can meet various needs in health care, nanotechnology and energy. Most works are currently focused on the individual bacterium as a chemical reactor. Our project, SynBioTIC, addresses a novel and more complex challenge: shape engineering, i.e. the redesign of natural morphogenesis toward a new kind of " developmental 3D printing ". Potential applications include organ growth, natural computing in biocircuits, or future vegetal houses. Using realistic agent-based simulations of bacterial mats, we experiment with mechanisms allowing cell assemblies to collectively self-repair and develop complex structures. To create multicellular organisms that exhibit specific shapes (a completely original task) we construe their development iteratively by combining basic processes such as homeostasis, segmentation, and controlled proliferation in silico. We use the E. coli simulator Gro 1 , a physico-chemical computation platform offering reaction-diffusion and collision dynamics solvers. The synthetic " bioware " of our model executes a set of rules, or " genome " , in each cell. Cells can differentiate into several predefined types associated with specific actions (divide, tumble, emit signal, die, etc.). Transitions between types are triggered by conditions involving internal and external sensors that detect various protein levels inside and around the cell. There is no direct molecular signaling between two neighboring bacteria, only indirect communication via morphogen diffusion and the mechanical constraints of 2D packing. In any case, the overall architecture emerges in a purely endogenous fashion. For now, cell behaviors are set by rules hand-coded in the Gro script language. Starting from a single bacterium, our artificial creatures execute a series of developmental stages. First, isotropic proliferation produces a roughly circular population characterized by homeostatic activity (black and white cores in Fig. 1a,b). This is based on leader cells emitting a morphogen, while other cells continually divide and die at the periphery where the morphogen concentra-1 Jang, Oishi, Egbert & Klavins (2012) ACS Syn Biol, 1:365–74. (a) (b) (c) Figure 1: Example of simulated organisms. (a,b) T and L shapes. Each limb of the organism stems from differentiated precursor cells. Starting from a four-pointed star, this makes it possible to introduce a " divergence of homology " through different parameter values in each limb, whether unequal lengths or complete silencing. (c) Three-pointed star shape. Here, limb growth is undifferentiated and the organism exhibits radial symmetry. tion drops. Then, the central region of the disc differentiates from the crown. Each cell also contains an oscillatory mechanism acting like a internal clock. In the crown, these oscillators are synchronized, i.e. characterized by a uniform phase. At this stage, a new wave of morphogen is triggered by a randomly activated cell on the crown, and rapidly propagates (suppressing any competitor wave). The encounter between the wave front and the current state of the oscillator determines whether each cell differentiates, and into what type. The period of oscillations controls the number of segments that can appear. Finally, precursor cells emerge at the periphery of these segments and stimulate new local proliferation , which eventually triggers limb growth in a way similar to the apical meristem of plant shoots (Fig. 1c). Applying this mechanism to two segments and two precursors , North and South, then on the equator that they form (areas of equal morphogen concentration), the system gives rise to a second pair, East and West, i.e. four differentiated seeds in total. This makes it possible to control the growth and features of single appendages. The L and T shapes of Fig. 1 exemplify this " divergence of homology " : some precursors are inhibited while others create limbs of varying size. Such morphogenetic phenotypes allow us to envision more complex shapes made of an array of cores and limbs, by iterating the above processes. Most importantly, they open the door to an evolutionary (" evo-devo ") exploration
Instabilités fluide-élastique dans l'échangeur de chaleur faisceaux de tubes et une réduction de modèle sans-Galerkin des systèmes multiphysiques
Heat exchangers are widely used in the power generation industries. The cross-flow type of heat exchangers are more common. The rate of heat transfer is enhanced by operating the heat exchangers at higher flow rates by means of the increased flow turbulence. Although, the high flow rate operations are favoured, there are side effects in terms of the flow-induced vibrations. In the last few decades, the topic (flow induced vibrations in heat exchanger tube bundles) is studied extensively, especially in order to understand the fluidelastic vibration. The preventive measures can be taken in other types of vibration mechanisms, such as the vortex induced vibrations and the acoustic resonance in tube bundles. The turbulence induced vibrations generally take long term to deteriorate the performance of heat exchangers, hence it involves a lesser risk of immediate damage to the heat exchangers. The failure due to the fluidelastic instability occurs suddenly and it can pose a serious risk in the plant operations. Besides the devastating nature of the fluidelastic instability, it is not well understood yet. In the first part of this thesis, the fluidelastic instability is explored by means of performing numerical simulations. The flow induced vibrations in the heat exchanger tube bundles are reviewed historically. The other mechanisms of vibrations, namely, vortex induced vibrations, turbulent buffeting and acoustic resonance in the tube arrays are briefed. In addition, thetheoretical models of the fluidelastic instability are revised in order to understand the different approaches used to model the instability. Computational Fluid Dynamics (CFD) simulations are performed, first by using the Unsteady Reynolds Averaged Navier-Stokes (URANS) approach of modeling the flow turbulence, in order to verify the capability of URANS modelsto predict the instability thresholds dynamically. Secondly, the transient nature of fluidelastic instability is investigated by means of the Large Eddy Simulations (LES) approach of the turbulence modeling. Although the LES approach is computationally expensive in comparison with the URANS approach, the dynamic interactions between the interstitial fluid flow and a single tube from an in-line tube bundle are well captured by the LES. The post-processing of the LES results is comprised of the dynamics of fluid forces acting on a single cylinder from an array, transient surface pressure profiles on the cylinder and the interstitial velocity flow fields as a consequence of the increasing flow velocity until the onset of fluidelastic instability. A mathematical model for the fluidelastic instability is developed based on the transient interaction between the interstitial flow through an in-line cylinders array and a single cylinder form the array. Although there are significant advances in the computers today, the Direct Numerical Simulations (DNS) of large dynamic systems are infeasible. Model reduction also known as Reduced-Order Modeling (ROM) has gained an importance in almost all fields of computational sciences. In the second part of the thesis, firstly, a short introduction to the model orderreduction is provided. The Proper Orthogonal Decomposition (POD) and Galerkin projections are commonly used in model reduction of the fluid systems. Almost all reduced-order models derived from the traditional POD-Galerkin ROM require the stability enablers. A novel Galerkin-free approach for model reduction of the Navier-Stokes equations is proposed in thisthesis. The method uses the periodicity of the POD time coefficients and a linear interpolation technique in order to construct the off-reference reduced solutions. A test case of the flow past a cylinder at low Reynolds numbers (Re ∼ 125) is used for the demonstration of the proposed ROM. In the formulation of the proposed Galerkin-free ROM, the variables of a dynamicalsystem are treated independently. Therefore, the method can be conveniently extended for the multi-physics dynamical systems. Lastly, the method of Galerkin-free ROM is applied to a fluid-structure interaction problem, where the moving mesh is a part of the solution state vector. A test case of the vortex induced vibration in a cylinder at Reynolds number Re = 100and the mass ratio as the controlling parameter is considered for the demonstration.Les échangeurs de chaleur sont largement utilisés dans les industries de production d’énergie. Le type d’échangeurs de chaleur à flux croisés sont les plus fréquents. Le taux de transfert de chaleur est amélioré en faisant fonctionner les échangeurs de chaleur à des débits plus élevés au moyen de la turbulence d’écoulement accrue. Bien que, les opérations de débit élevé sont favorisés, il y des effets secondaires en termes de vibrations induites par l’écoulement. Dans les dernières décennies, le sujet (débit vibrations induites dans l’échangeur de chaleur des faisceaux de tubes) a été étudié en profondeur, en particulier afin de comprendre les vibrations fluide-élastique. Des mesures préventives peuvent être prises dans d’autres types de mécanismes de vibration, comme les vibrations induites par vortex et la résonance acoustiquedans les faisceaux de tubes. Les vibrations induites par turbulence prennent généralement longtemps à détériorer les structures des échangeurs de chaleur, d’où elle implique un risque moindre de dommages immédiats aux échangeurs de chaleur. L’échec dû à l’instabilité fluide-élastique se produit dans une question d’heures et il peut poser un risque grave dans les opérations de l’usine; alors même que la nature dévastatrice. De l’instabilité fluide-élastique n’est pas encore bien comprise. Dans la première partie de cette thèse, l’instabilité fluide-élastique est explorée en utilisant des simulations numérique. Les vibrations induites par l’écoulement dans les faisceaux de tubes sont examinés historiquement. Les autres mécanismes de vibrations, à savoir, des vibrations induites par vortex, et par la turbulente et la résonance acoustique dans les fais-ceaux de tubes sont bien documentés. De plus, les modèles théoriques de l’instabilité fluide-élastique sont examinés. Les simulations de Mécanique des Fluides Numérique (MFN) ou en anglais Computational Fluid Dynamics (CFD) sont réalisées, d’abord en utilisant l’approache Unsteady Reynolds Averaged Navier-Stokes (URANS) pour la modélisation de la turbulence,afin de vérifier la capacité des modèles de URANS à prédire les seuils d’instabilité dynamique. Deuxièmement, la nature transitoire de l’instabilité fluide-élastique est étudiée au moyen de la Simulation Grandes Échelles (Large Eddy Simulation LES) des structure turbulent. Bien que l’approche LES est chère en comparaison avec l’approche URANS, les interactions dy-namiques entre le flux de liquide interstitiel et un seul tube à partir d’un faisceau de tubes en ligne sont bien capturés par la LES. Le post-traitement des résultats LES composée de la dynamique des forces du fluide agissant sur un seul cylindre dans un groupe, les profils de pression sur le cylindre et les champs d’écoulement de vitesse interstitiels en augmentant lavitesse d’écoulement jusqu’à l’apparition de l’instabilité fluide-élastique. Un modèle mathématique pour l’instabilité fluide-élastique est développé sur la base de l’interaction transitoire entre le débit interstitiel à travers une gamme de cylindres en ligne et une seule forme de cylindre du faisceau. Bien qu’il y ait des progrès significatifs dans les capacités de calcul, la simulation numérique direct (Direct Numerical Simulation DNS) des grands systémes dynamique sont touhours infaisable. La Réduction de modèles aussi connue comme Reduced Order Modeling (ROM) a acquis une importance dans presque tous les domaines des sciences informatiques. Dans ladeuxième partie de la thèse, d’une part, une introduction à la réduction de l’ordre de modèle est fournie. La décomposition en modes propres orthogonaux (Proper Orthogonal Decomposition POD) et les projections de type Galerkin sont couramment utilisées dans la réduction de modèle des écoulement de fluides. Presque tous les modèles d’ordre réduit provenant de la technique POD-Galerkin exigent des l’introduction de stabilisations. Une nouvelle approche de type “Galerkin-free" pour la réduction de modèle des équations de Navier-Stokes est proposée dans cette thèse. La méthode utilise la périodicité des coefficients temporelle de POD et une technique d’interpolation linéaire afin de construiredes solutions d’ordre réduit. Le cas test de l’écoulement autour d’un cylindre à faible nombre de Reynolds (Re ∼ 125) est utilisé pour la démonstration de modéle d’ordre réduit proposé. Dans la formulation de modéle d’ordre réduit “Galerkin-free" POD, les variables d’un système dynamique sont traitées indépendamment. Par conséquent, la méthode peut être facile-ment étendue aux systèmes dynamiques multi-physiques. Enfin, la technique de Galerkin-free modéle d’ordre réduit est appliquée à un problème d’interaction fluide-structure, où la maille mobile fait partie du vecteur d’état de la solution. Un cas test de vibrations d’induite par vortex d’un cylindre pour un nombre de Reynolds de 100 avec le rapport de masse comme paramètre de contrôle est considéré pour la démonstration
Accurate prediction of the statistics of repetitions in random sequences : a case study in Archae genomes
Repetitive patterns in genomic sequences have a great biological significance and also algorithmic implications. This paper contributes to a precise knowledge of the length of repetitions in a random sequence. Results are easily computable and are shown accurate for common lengths of sequences. As an application, the sample case of Archae genomes illustrates how biological sequences may differ from random sequences