DMT1 Inhibitors Kill Cancer Stem Cells by Blocking Lysosomal Iron Translocation

Cancer stem cells (CSC) constitute a cell subpopulation in solid tumors that is responsible for resistance to conventional chemotherapy, metastasis and cancer relapse. The natural product Salinomycin can selectively target this cell niche by directly interacting with lysosomal iron, taking advantage of upregulated iron homeostasis in CSC. Here, inhibitors of the divalent metal transporter 1 (DMT1) have been identified that selectively target CSC by blocking lysosomal iron translocation. This leads to lysosomal iron accumulation, production of reactive oxygen species and cell death with features of ferroptosis. DMT1 inhibitors selectively target CSC in primary cancer cells and circulating tumor cells, demonstrating the physiological relevance of this strategy. Taken together, this opens up opportunities to tackle unmet needs in anti-cancer therapy.     

Transient modal radiation of axisymmetric sources: Application to loudspeakers

The present study proposes a transient model of the acoustic radiation of axisymmetric structures. The pressure field is approximated by the Rayleigh integral corresponding to a monopole source distribution over the non-planar vibrating surface. The displacement field is expanded on the linear modes of the structure and a change of variables in the Rayleigh integral is then proposed in the case of a monotonic profile function to compute the Spatial Impulse Response associated to each mode of vibration efficiently. The results are compared to the formulation obtained in the case of planar and spherical sources. The method of calculation is then derived in the case of a typical loudspeaker profile (association of a truncated cone with a spherical cap). Finally, the present approach is used to estimate the nonlinear radiation pattern of a prototype loudspeaker and predictions are compared to measurements in anechoic room.     

Homogenization of divergence-form operators with lower-order terms in random media

The probabilistic machinery (Central Limit Theorem, Feynman-Kac formula and Girsanov Theorem) is used to study the homogenization property for PDE with second-order partial differential operator in divergence-form whose coefficients are stationary, ergodic random fields. Furthermore, we use the theory of Dirichlet forms, so that the only conditions required on the coefficients are non-degeneracy and boundedness. Received: 27 August 1999 / Revised version: 27 October 2000 / Published online: 26 April 2001     

An improved On-Surface Radiation Condition for acoustic scattering problems in the high-frequency spectrum

This Note addresses the derivation of an improved On-Surface Radiation Condition for the numerical solution of the exterior Helmholtz equation at high-frequencies. This condition is built as an approximation of the Neumann-to-Dirichlet map by using a local regularization of its principal classical symbol in the gliding zone for modelling the creeping waves. The numerical simulation of this pseudodifferential operator is efficiently realized with a linear cost according to the dimension of the boundary element approximation space using suitable complex Padé approximants. A numerical example is provided. To cite this article: X. Antoine et al., C. R. Acad. Sci. Paris, Ser. I 340 (2005).     

Estimation of the bias parameter of the skew random walk and application to the skew Brownian motion

We study the asymptotic property of simple estimator of the parameter of a skew Brownian motion when one observes its positions on a fixed grid—or equivalently of a simple random walk with a bias at 0. This estimator, nothing more than the maximum likelihood estimator, is based only on the number of passages of the random walk at 0. It is very simple to set up, is consistent and is asymptotically mixed normal. We believe that this simplified framework is helpful to understand the asymptotic behavior of the maximum likelihood of the skew Brownian motion observed at discrete times which is studied in a companion paper.     

Toute forme modérément ramifiée d’un polydisque ouvert est triviale

Let k be a complete, non-Archimedean field and let X be a k-analytic space. Assume that there exists a finite, tamely ramified extension L of k such that X _L is isomorphic to an open polydisc over L ; we prove that X is itself isomorphic to an open polydisc over k. The proof consists in using the graded reduction (a notion which is due to Temkin) of the algebra of functions on X, together with some graded counterparts of classical commutative algebra results : Nakayama’s lemma, going-up theorem, basic notions about étale algebras, etc.     

Stability of Generalized Transition Fronts

We study the qualitative properties of the generalized transition fronts for the reaction–diffusion equations with the spatially inhomogeneous nonlinearity of the ignition type. We show that transition fronts are unique up to translation in time and are globally exponentially stable for the solutions of the Cauchy problem. The results hold for reaction rates that have arbitrary spatial variations provided that the rate is uniformly positive and bounded from above.