Cell death and life in cancer: mathematical modeling of cell fate decisions

Tumor development is characterized by a compromised balance between cell life and death decision mechanisms, which are tighly regulated in normal cells. Understanding this process provides insights for developing new treatments for fighting with cancer. We present a study of a mathematical model describing cellular choice between survival and two alternative cell death modalities: apoptosis and necrosis. The model is implemented in discrete modeling formalism and allows to predict probabilities of having a particular cellular phenotype in response to engagement of cell death receptors. Using an original parameter sensitivity analysis developed for discrete dynamic systems, we determine the critical parameters affecting cellular fate decision variables that appear to be critical in the cellular fate decision and discuss how they are exploited by existing cancer therapies

Interactive multimodal Path Planning in immersion

Recent studies have defined interactive path plan- ners for simulations involving a human operator. Such path planners enable a human operator to share control with an automatic planner and are based on Robotics and Virtual Reality (VR) methods. This paper proposes a novel architecture for this interactive planner. It enhances interaction with the user by adding topological and semantic representations to the purely geometric model traditionally used

A multi-layer approach of interactive path planning for assisted manipulation in virtual reality

This work considers Virtual Reality (VR) applications dealing with objects manipulation (such as industrial product assembly, disassembly or maintenance simulation). For such applications, the operator performing the simulation can be assisted by path planning techniques from the robotics research field. A novel automatic path planner involving geometrical, topological and semantic information of the environment is proposed for the guidance of the user through a haptic device. The interaction allows on one hand, the automatic path planner providing assistance to the human operator, and on the other hand, the human operator to reset the whole planning process suggesting a better suited path. Control sharing techniques are used to improve the assisted manipulation ergonomics by dynamically balancing the automatic path planner authority according to the operator involvement in the task, and by predicting user’s intent to integrate it as early as possible in the planning process

A hierarchic approach for path planning in virtual reality.

This work considers path-planning processes for manipu- lation tasks such as assembly, maintenance or disassem- bly in a virtual reality (VR) context. The approach con- sists in providing a collaborative system associating a user immersed in VR and an automatic path planning process. It is based on semantic, topological and geometric representations of the environment and the planning process is split in two phases: coarse and fine planning. The automatic planner suggests a path to the user and guides him trough a haptic device. The user can escape from the proposed solution if he wants to explore a possible better way. In this case, the interactive system detects the users intention and computes in real-time a new path starting from the users guess. Experiments illustrate the different aspects of the approach: multi-representation of the en- vironment, path planning process, users intent prediction and control sharing

Multi-layer path planning control for the simulation of manipulation tasks : involving semantics and topology

The industrial and research communities show increasing interest in using automatic path planning techniques for the simulation of manipulation tasks. Automatic path planning, largely explored by the robotics community over the past 30 years, computes the trajectories of robots or manipulated parts. However, as techniques developed so far use mostly purely (and large) geometric models, they may fail, produce a trajectory of little relevance, or lead to very high computation times, when facing complex or very constrained environments. Involving higher abstraction level information should lead to better relevance of the simulation. In this paper, we propose a novel path planning technique relying on an original multi-layer environment model containing geometrical, topological and semantic layers. A first coarse planning step at the topological and semantic layers and a fine planning step at the local and semantically characterized geometrical layer form the path planning process. Experimental full-scale results show increased control on the planning process, leading to much lower computation times and increased relevance of the computed trajectory

Using virtual reality and 3D industrial numerical models for immersive interactive checklists

At the different stages of the PLM, companies develop numerous checklist-based procedures involving prototype inspection and testing. Besides, techniques from CAD, 3D imaging, animation and virtual reality now form a mature set of tools for industrial applications. The work presented in this article develops a unique framework for immersive checklist-based project reviews that applies to all steps of the PLM. It combines immersive navigation in the checklist, virtual experiments when needed and multimedia update of the checklist. It provides a generic tool, independent of the considered checklist, relies on the integration of various VR tools and concepts, in a modular way, and uses an original gesture recognition. Feasibility experiments are presented, validating the benefits of the approach

A multi-layer approach for interactive path planning control.

This work considers path-planning processes for manipulation tasks such as assembly, maintenance or disassembly in a Virtual Reality (VR) context. The approach consists in providing a collaborative system associating a user immersed in VR and an automatic path planning process. It is based on semantic, topological and geometric representations of the environment and the planning process is split in two phases: coarse and fine planning. The automatic planner suggests a path to the user and guides him trough a haptic device. The user can escape from the proposed solution if he wants to explore a possible better way. In this case, the interactive system detects the user’s intention in real-time and computes a new path starting from the user’s guess. Experiments illustrate the different aspects of the approach: multi-representation of the environment, path planning process, user’s intent prediction and control sharing

Mathematical Modelling of Cell-Fate Decision in Response to Death Receptor Engagement

Cytokines such as TNF and FASL can trigger death or survival depending on cell lines and cellular conditions. The mechanistic details of how a cell chooses among these cell fates are still unclear. The understanding of these processes is important since they are altered in many diseases, including cancer and AIDS. Using a discrete modelling formalism, we present a mathematical model of cell fate decision recapitulating and integrating the most consistent facts extracted from the literature. This model provides a generic high-level view of the interplays between NFκB pro-survival pathway, RIP1-dependent necrosis, and the apoptosis pathway in response to death receptor-mediated signals. Wild type simulations demonstrate robust segregation of cellular responses to receptor engagement. Model simulations recapitulate documented phenotypes of protein knockdowns and enable the prediction of the effects of novel knockdowns. In silico experiments simulate the outcomes following ligand removal at different stages, and suggest experimental approaches to further validate and specialise the model for particular cell types. We also propose a reduced conceptual model implementing the logic of the decision process. This analysis gives specific predictions regarding cross-talks between the three pathways, as well as the transient role of RIP1 protein in necrosis, and confirms the phenotypes of novel perturbations. Our wild type and mutant simulations provide novel insights to restore apoptosis in defective cells. The model analysis expands our understanding of how cell fate decision is made. Moreover, our current model can be used to assess contradictory or controversial data from the literature. Ultimately, it constitutes a valuable reasoning tool to delineate novel experiments

Régulation redox des facteurs des transcription de la famille CNC-bZip Nrf2 et Bach2.

Les espèces chimiques dérivées par réduction incomplète de l'oxygène, les ROS pour « Reactive Oxygen Species », et espèces réactives dérivées de l'azote, les RNS pour « Reactive Nitrogen Species », sont potentiellement toxiques pour les cellules, car leur pouvoir oxydant leur confère une grande réactivité sur la plupart des molécules biologiques. Des systèmes cellulaires existent, qui assurent leur maintien à des concentrations non toxiques. Cependant, l'oxygène est nécessaire aux cellules pour son rôle d'accepteur final d'électrons dans la chaîne respiratoire, et certains ROS ou RNS sont nécessaires à l'accomplissement de diverses fonctions biologiques. En particulier, l'H2O2 participe en tant que second messager à la signalisation cellulaire en aval de l'engagement de certains récepteurs à des facteurs de croissance. Notre objectif est de documenter le rôle possible de ces espèces réactives dans la signalisation cellulaire chez les mammifères, en mettant en évidence des protéines cibles de l'oxydation, et en étudiant l'effet fonctionnel de ces oxydations. Nous avons choisi d'étudier la formation de ponts disulfures en réponse peroxyde d'hydrogène H2O2 et au monoxyde d'azote NO dans la protéine Keap1, qui régule l'activité du facteur de transcription Nrf2, et le facteur de transcription Bach2. Nrf2 et Bach2 sont deux facteurs de transcription de la famille des protéines à CNC-bZip, et contrôlent tous deux l'expression de gènes régulés en cis par des séquences de type ARE, pour « Antioxidant Responsive Element"