Activation of BMP-Smad1/5/8 Signaling Promotes Survival of Retinal Ganglion Cells after Damage In Vivo

While the essential role of bone morphogenetic protein (BMP) signaling in nervous system development is well established, its function in the adult CNS is poorly understood. We investigated the role of BMP signaling in the adult mouse retina following damage in vivo. Intravitreal injection of N-Methyl-D-aspartic acid (NMDA) induced extensive retinal ganglion cell death by 2 days. During this period, BMP2, -4 and -7 were upregulated, leading to phosphorylation of the downstream effector, Smad1/5/8 in the inner retina, including in retinal ganglion cells. Expression of Inhibitor of differentiation 1 (Id1; a known BMP-Smad1/5/8 target) was also upregulated in the retina. This activation of BMP-Smad1/5/8 signaling was also observed following light damage, suggesting that it is a general response to retinal injuries. Co-injection of BMP inhibitors with NMDA effectively blocked the damage-induced BMP-Smad1/5/8 activation and led to further cell death of retinal ganglion cells, when compared with NMDA injection alone. Moreover, treatment of the retina with exogenous BMP4 along with NMDA damage led to a significant rescue of retinal ganglion cells. These data demonstrate that BMP-Smad1/5/8 signaling is neuroprotective for retinal ganglion cells after damage, and suggest that stimulation of this pathway can serve as a potential target for neuroprotective therapies in retinal ganglion cell diseases, such as glaucoma

Web Usage Mining: Sequential Pattern Extraction with a Very Low Support

Abstract. The goal of this work is to increase the relevance and the interestingness of patterns discovered by a Web Usage Mining process. Indeed, the sequential patterns extracted on web log files, unless they are found under constraints, often lack interest because of their obvious content. Our goal is to discover minority users ’ behaviors having a coherence which we want to be aware of (like hacking activities on the Web site or a users ’ activity limited to a specific part of the Web site). By means of a clustering method on the extracted sequential patterns, we propose a recursive division of the problem. The developed clustering method is based on patterns summaries and neural networks. Our experiments show that we obtain the targeted patterns whereas their extraction by means of a classical process is impossible because of a very weak support (down to 0.006%). The diversity of users ’ behaviors is so large that the minority ones are both numerous and difficult to locate

Broadway: A Case-Based System for Cooperative Information Browsing on the World-Wide-Web.

: The World Wide Web is a huge hypermedia where finding relevant documents is not an easy task. In this paper, we present our case-based system for cooperative information browsing, called BROADWAY. BROADWAY follows a group of users during their navigations on the WWW (proxy-based architecture) and advise them by displaying a list of potentially relevant documents to visit next. BROADWAY uses case-based reasoning to reuse precise experiences derived from past navigations with a time-extended situation assessment: the advice are based mainly on similarity of ordered sequence of past accessed documents. In addition, the dynamic of the WWW is addressed in the reuse step and with a specific method for case forgetting. 1. Introduction The World Wide Web (WWW) [15] is an hypermedia of heterogeneous and dynamic documents. This virtual space is growing more and more every day, offering to the user a huge amount of data [4]. Two kinds of methods can be used to locate a relevant document throu..

Représentation et traitement pratique de la flexibilité dans les problèmes sous contraintes

* INRA - Unité de Biométrie, Centre de Toulouse (FRA) Diffusion du document : INRA - Unité de Biométrie, Centre de Toulouse (FRA)National audienceEn premier lieu, après un rapide rappel des principales définitions relatives aux CSP, nous donnons une description des applications nécessitant ou ayant nécessité une extension du formalisme classique. Différentes origines de la flexibilité sont ensuite recensées en s'appuyant sur ces applications ; on distingue principalement les causes suivantes : existence de préférences, nature imprécise et incertaine des connaissances, complexité d'un problème nécessitant une hiérarchisation et évolution dans le temps. Afin d'illustrer ces formes de flexibilité, nous présentons un problème typique d'emploi du temps. Nous abordons ensuite le problème du traitement de la flexibilité. Pour chacune des origines, nous discutons des énoncés de problèmes sous-jacents et des différentes approches envisageables. La conclusion donne une synthèse des besoins soulevés. Une série d'annexes est consacrée à la résolution de CSP flexibles. Après un rapide état de l'art, nous présentons les travaux réalisés par les membres du projet constituant des éléments de réponse pour le traitement de certains cas de flexibilité