Mines ParisTech

About: Mines ParisTech is a education organization based out in Paris, France. It is known for research contribution in the topics: Finite element method & Microstructure. The organization has 6564 authors who have published 11676 publications receiving 359898 citations. The organization is also known as: École nationale supérieure des mines de Paris & École des mines de Paris.

Canards et enlacements

Abstract: On considere le probleme de la convergence, pour e positif tendant vers zero, des champs de vecteurs, notes Ee, sur R 3 du type x˙=f(x,y,z,e), y˙=g(x,y,z,e), ez=h(x,y,z,e) Ce probleme est connu sous le nom de perturbation singuliere, ou de probleme a deux echelles de temps Le probleme de la convergence de (Ee) vers un champ (E 0 ) est un probleme de convergence de trajectoires Soit (Me) une famille de points de R 3 telle que Me converge vers un point M 0 Soit γe la trajectoire du systeme (Ee) issue du point Me La famille (γe) converge-t-elle vers une courbe γ 0 ? Si oui, en quel sens? au sens de la convergence uniforme sur tout compact des fonctions du temps? au sens de la convergence C 1 ?… Reciproquement, soit γ 0 une «trajectoire de (E 0 )» Peut-on trouver une suite de conditions initiales Me telle que la trajectoire de (Ee) issue de Me converge vers γ 0 ?… On utilise des outils non standard pour analyser ce type de question

A Modeling Approach to Explain Mutually Exclusive and Co-Occurring Genetic Alterations in Bladder Tumorigenesis

Abstract: Relationships between genetic alterations, such as co-occurrence or mutual exclusivity, are often observed in cancer, where their understanding may provide new insights into etiology and clinical management. In this study, we combined statistical analyses and computational modeling to explain patterns of genetic alterations seen in 178 patients with bladder tumors (either muscle-invasive or non-muscle-invasive). A statistical analysis on frequently altered genes identified pair associations, including co-occurrence or mutual exclusivity. Focusing on genetic alterations of protein-coding genes involved in growth factor receptor signaling, cell cycle, and apoptosis entry, we complemented this analysis with a literature search to focus on nine pairs of genetic alterations of our dataset, with subsequent verification in three other datasets available publicly. To understand the reasons and contexts of these patterns of associations while accounting for the dynamics of associated signaling pathways, we built a logical model. This model was validated first on published mutant mice data, then used to study patterns and to draw conclusions on counter-intuitive observations, allowing one to formulate predictions about conditions where combining genetic alterations benefits tumorigenesis. For example, while CDKN2A homozygous deletions occur in a context of FGFR3-activating mutations, our model suggests that additional PIK3CA mutation or p21CIP deletion would greatly favor invasiveness. Furthermore, the model sheds light on the temporal orders of gene alterations, for example, showing how mutual exclusivity of FGFR3 and TP53 mutations is interpretable if FGFR3 is mutated first. Overall, our work shows how to predict combinations of the major gene alterations leading to invasiveness through two main progression pathways in bladder cancer.