Universality of clone dynamics during tissue development.

The emergence of complex organs is driven by the coordinated proliferation, migration and differentiation of precursor cells. The fate behaviour of these cells is reflected in the time evolution their progeny, termed clones, which serve as a key experimental observable. In adult tissues, where cell dynamics is constrained by the condition of homeostasis, clonal tracing studies based on transgenic animal models have advanced our understanding of cell fate behaviour and its dysregulation in disease (1, 2). But what can be learned from clonal dynamics in development, where the spatial cohesiveness of clones is impaired by tissue deformations during tissue growth? Drawing on the results of clonal tracing studies, we show that, despite the complexity of organ development, clonal dynamics may converge to a critical state characterized by universal scaling behaviour of clone sizes. By mapping clonal dynamics onto a generalization of the classical theory of aerosols, we elucidate the origin and range of scaling behaviours and show how the identification of universal scaling dependences may allow lineage-specific information to be distilled from experiments. Our study shows the emergence of core concepts of statistical physics in an unexpected context, identifying cellular systems as a laboratory to study non-equilibrium statistical physics.Wellcome Trus

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Assimilation des observations pour la modélisation de la qualité de l'air

Lors de ce travail de thèse, nous nous sommes focalisés sur l'assimilation des observations d'ozone de surface au sein du modèle CHIMERE sur le continent Européen à l'aide d'un filtre de Kalman d'Ensemble. Une première expérience d'assimilation a été présentée et évaluée pour un épisode de pollution photochimique. La comparaison entre l'analyse et la simulation de référence montre d'excellents résultats. On note en effet une amélioration pour l'ensemble des indicateurs statistiques et pour tous les types de stations. A partir de cette expérience, différents paramètres de l'algorithme d'assimilation ont été optimisés, en particulier la variance des erreurs d'observation et la variance/covariance de l'erreur d'ébauche. Nous avons alors employé différents diagnostics a posteriori réalisés dans l'espace des observations. Ces diagnostics nous ont permis d'estimer l'erreur modèle et d'observation et de vérifier leur cohérence avec les innovations obtenues. Enfin, nous avons étudié la possibilité de prescrire les valeurs diagnostiquées de ces erreurs au cours des cycles d'analyse et de prévisions. Il apparaît que les erreurs ont un cycle diurne marqué qu'il faut prendre en compte et qu'une part importante de l'erreur est causée par la représentativité spatiale. Par ailleurs, nous avons développé une approche basée sur la perturbation des paramètres physiques du modèle, mais qui ne génère pas assez de variabilité. Finalement, nous avons pu montrer la robustesse de ce système d'assimilation et la reproductibilité des résultats par rapport à ces paramètres, pour l'épisode de pollution et pour une expérience d'assimilation sur un été.In this thesis, an Ensemble Kalman Filter has been coupled to the CHIMERE chemical transport model in order to assimilate ozone ground measurements at continental scale. A first assimilation experiment during a summertime photochemical pollution episode is presented and evaluated. The comparison between the analysis and the reference run shows excellent results. We note for the analysis an improvement regarding to the whole set of statistical indicators and for all stations types. Based on this experiment, different parameters of the data assimilation algorithm were optimized, in particular the observation space were employed. These diagnostics were used to estimate model and observation errors and to verify that they were consistent with obtained innovations. Finally, we investigated the application of diagnosed error values during an analysis-forecast cycle. It appears that errors have a clear diurnal cycle which needs to be taken into account and that an important part of these errors related to the spatial representativeness. We also developed an approach based on perturbations of model physical parameters but which fails in generating enough variability in the model ensemble. Finally, we demonstrate the robustness of the data assimilation system and reproducibility of the results with respect to the chosen parameters, for the specific pollution and for an entire summer assimilation period.PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Central structures involved in the endocrine response to the first contact with the sexual partner or its odor in young and sexually naive anoestrus ewes: An immunohistochemistry study

National audienc

Capacities of Migrating CD1b + Lymph Dendritic Cells to Present Salmonella Antigens to Naive T Cells

Dendritic cells (DCs) are well known as professional antigen-presenting cells (APC) able to initiate specific T-cell responses to pathogens in lymph nodes (LN) draining the site of infection. However, the respective contribution of migratory and LNresident DCs in this process remains unclear. As DC subsets represent important targets for vaccination strategies, more precise knowledge of DC subsets able to present vaccine antigens to T cells efficiently is required. To investigate the capacities of DCs migrating in the lymph (L-DCs) to initiate a specific T-cell response, we used physiologically generated DCs collected from a pseudoafferent lymphatic cannulation model in sheep. The CD1b + L-DCs were assessed for presenting antigens from the vaccine attenuated strain of Salmonella enterica serovar Abortusovis. CD1b + L-DCs were able to phagocytose, process and to present efficiently Salmonella antigens to effector/memory T cells in vitro. They were shown to be efficient APC for the priming of allogeneic naive T cells associated with inducing both IFN-c and IL-4 responses. They were also efficient in presenting Salmonella antigens to autologous naive T cells associated with inducing both IFN-c and IL-10 responses. The capacities of L-DCs to process and present Salmonella antigens to T cells were investigated in vivo after conjunctival inoculation of Salmonella. The CD1b + L-DCs collected after inoculation were able to induce the proliferative response of CD4 + T cells suggesting the in vivo capture of Salmonella antigens by the CD1b + L-DCs, and their potential to present them directly to CD4 + T cells. In this study, CD1b + L-DCs present potential characteristics of APC to initiate b

Application of the Wave Finite Element method to the computation of the response of a ballastless railway track, comparison with on-site measurements

Dynamics of railway tracks have been studied for a long time. Many authors proposed analytical or numerical models to compute the dynamic response of the tracks. Numerical models often use the track periodicity to reduce the size of the problem. Among these numerical methods, the Wave Finite Element (WFE) method was designed to compute the dynamics of periodic structures composed of identical patterns. It was successfully applied to simplied models of railway tracks subjected to dierent types of loads. In these studies, tracks are modeled by periodically supported beams. In order to give access to stresses and strains at a ne scale, a much ner representation is needed. This article presents a WFE computation of the dynamics of a ballastless railway track subjected to constant moving loads. In the presented computation the rail, the underlying slab and the support system are all represented in three dimensions. In order to validate this method, the obtained results are compared to experimental strain measurements

A COMPARISON OF BEAM MODELS FOR THE DYNAMICS OF RAILWAY TRACKS ON A NON-UNIFORM VISCOELASTIC FOUNDATION

International audienceMany numerical or analytical methods have been developed to compute the response of a railway track on a uniform foundation. The rail can then be modelled by different beam models. It was shown that for uniform railway tracks, Euler beam model and Timoshenko beam model give close results. In the case of damaged railway track components, the defaults can cause higher displacements of the rail leading to higher shears. Thus, in this case, the Timoshenko beam model can be more interesting. In this paper, a semi-analytical model for a railway track resting on a non-uniform foundation is proposed where the rail is modelled by a Timoshenko beam. Then, the results obtained with Timoshenko beam model and Euler Bernoulli beam model are compared for both a uniform railway track and a damaged railway track

Identification of new antigen candidates for the early diagnosis of Mycobacterium avium subsp. paratuberculosis infection in goats

International audienceCurrently Mycobacterium avium subsp. paratuberculosis (MAP) infection is diagnosed through indirect tests based on the immune response induced by the infection. The antigens commonly used in IFN-γ release assays (IGRA) are purified protein derivative tuberculins (PPD). However, PPDs, lack both specificity (Sp) and sensitivity (Se) in the early phase of infection. This study investigated the potential of 16 MAP recombinant proteins and five lipids to elicit the release of IFN-γ in goats from herds with or without a history of paratuberculosis. Ten recombinant proteins were selected as potential candidates for the detection of MAP infection in young goats. They were found to detect 25 to 75% of infected shedder (IS) and infected non-shedder (INS) kids younger than 10 months of age. In comparison, PPD was shown to detect only 10% of INS and no IS kids. For seven antigens, Se (21–33%) and Sp (≥ 90%) of IGRA were shown to be comparable with PPD at 20 months old. Only three antigens were suitable candidates to detect IS adult goats, although Se was lower than that obtained with PPD. In paratuberculosis-free herds, IGRA results were negative in 97% of indoor goats and 86% of outdoor goats using the 10 antigens. However, 22 to 44% of one-year-old outdoor goats were positive suggesting that they may be infected. In conclusion, this study showed that ten MAP recombinant proteins are potential candidates for early detection of MAP infected goats. Combining these antigens could form a possible set of MAP antigens to optimize the Se of caprine IGRA

Computation of the response of damaged railway tracks subjected to constant moving loads: numerical results obtained with the wave finite element method and analytical results

Railway tracks are subjected to heavy repeated loads due to the train traffic. These loads can damage the track and especially its supports. To compute the behavior of railway tracks, many authors used a periodicity hypothesis, which is broken by the presence of a damaged zone. Researchers proposed different analytical or numerical methods to compute the dynamics of such structures. Analytical methods permit low numerical cost computations of the track dynamics, but are limited to very simple representations of the track, whereas numerical methods allow the use of much more detailed representations of the track but with higher numerical cost. In most regions, railway tracks can be modeled as periodic structures. Several methods take advantage of this periodicity to limit the numerical cost for the computation of the track dynamics. Among these methods, the Wave Finite Element (WFE) method was initially created to compute free vibrations in periodic structure. This method was improved to compute the dynamic response of periodic structures subjected to any kind of loads. In recent development, the authors adapted the WFE method to compute the response of structure composed of two semi infinite periodic zones linked by a central zone with different mechanical properties. In this paper, the results obtained with an analytical method will be compared to results obtained with the WFE method for the computation of the dynamic responses of different ballastless railway tracks such as healthy, damaged tracks. In these computations, the tracks will be subjected to constant moving load representing the load applied by a train wheel. In the WFE results, the rail, the supports, and the supporting concrete slabs are represented with a three-dimensional model. A special focus will be made on the state of stress of the different materials which constitute the tracks. A failure criterion will be computed at components scale for the different tracks simulated. This criterion can then be used to compute the likeliness of long-term fatigue of the track components