Sensitivity analysis of oscillator models in the space of phase-response curves: Oscillators as open systems

Oscillator models are central to the study of system properties such as entrainment or synchronization. Due to their nonlinear nature, few system-theoretic tools exist to analyze those models. The paper develops a sensitivity analysis for phase-response curves, a fundamental one-dimensional phase reduction of oscillator models. The proposed theoretical and numerical analysis tools are illustrated on several system-theoretic questions and models arising in the biology of cellular rhythms

Kick synchronization versus diffusive synchronization

The paper provides an introductory discussion about two fundamental models of oscillator synchronization: the (continuous-time) diffusive model, that dominates the mathematical literature on synchronization, and the (hybrid) kick model, that accounts for most popular examples of synchronization, but for which only few theoretical results exist. The paper stresses fundamental differences between the two models, such as the different contraction measures underlying the analysis, as well as important analogies that can be drawn in the limit of weak coupling.Peer reviewe

Elucidating the Altered Transcriptional Programs in Breast Cancer using Independent Component Analysis

The quantity of mRNA transcripts in a cell is determined by a complex interplay of cooperative and counteracting biological processes. Independent Component Analysis (ICA) is one of a few number of unsupervised algorithms that have been applied to microarray gene expression data in an attempt to understand phenotype differences in terms of changes in the activation/inhibition patterns of biological pathways. While the ICA model has been shown to outperform other linear representations of the data such as Principal Components Analysis (PCA), a validation using explicit pathway and regulatory element information has not yet been performed. We apply a range of popular ICA algorithms to six of the largest microarray cancer datasets and use pathway-knowledge and regulatory-element databases for validation. We show that ICA outperforms PCA and clustering-based methods in that ICA components map closer to known cancer-related pathways, regulatory modules, and cancer phenotypes. Furthermore, we identify cancer signalling and oncogenic pathways and regulatory modules that play a prominent role in breast cancer and relate the differential activation patterns of these to breast cancer phenotypes. Importantly, we find novel associations linking immune response and epithelial–mesenchymal transition pathways with estrogen receptor status and histological grade, respectively. In addition, we find associations linking the activity levels of biological pathways and transcription factors (NF1 and NFAT) with clinical outcome in breast cancer. ICA provides a framework for a more biologically relevant interpretation of genomewide transcriptomic data. Adopting ICA as the analysis tool of choice will help understand the phenotype–pathway relationship and thus help elucidate the molecular taxonomy of heterogeneous cancers and of other complex genetic diseases

Drastic Vegetation Change in the Guajira Peninsula (Colombia) during the Neogene

Dry biomes occupy ~35% of the landscape in the Neotropics, but these are heavily human-disturbed. In spite of their importance, we still do not fully understand their origins and how they are sustained. The Guajira Peninsula in northern Colombia is dominated by dry biomes and has a rich Neogene fossil record. Here, we have analyzed its changes in vegetation and precipitation during the Neogene using a fossil pollen and spore dataset of 20 samples taken from a well and we also dated the stratigraphic sequence using microfossils. In addition, we analyzed the pollen and spore contents of 10 Holocene samples to establish a modern baseline for comparison with the Neogene as well as a study of the modern vegetation to assess both its spatial distribution and anthropic disturbances during the initial stages of European colonization. The section was dated to span from the latest Oligocene to the early Miocene (~24.2 to 17.3 Ma), with the Oligocene/Miocene boundary being in the lower Uitpa Formation. The early Miocene vegetation is dominated by a rainforest biome with a mean annual precipitation of ~2,000 mm/yr, which strongly contrasts with Guajira\u27s modern xerophytic vegetation and a precipitation of ~300 mm/yr. The shift to the dry modern vegetation probably occurred over the past three millions years, but the mechanism that led to this change is still uncertain. Global circulation models that include the vegetation could explain the ancient climate of Guajira, but further work is required to assess the feedbacks of vegetation, precipitation, and CO2

Un système de télémédecine pour les seniors

National audienceDans le cadre d'une thèse menée au sein du Centre de recherche le Loria rattaché à l'INPL (Institut National Polytechnique de Lorraine) à Nancy, un concept de maison intelligente a été développé offrant un système de télésanté et téléassistance. L'objectif est de mettre au point une architecture originale qui intègre plusieurs réseaux de capteurs statiques et mobiles et de réseaux de caméras sans fil permettant le suivi médical à distance, l'assistance à la vie quotidienne et l'accès à des différents services. Le segment de population ciblé est les personnes âgées et à mobilité réduite. En utilisant ce système, l'association MEDeTIC, offre un nouveau concept de maisons intelligente pour les personnes du troisième âge, appelées "Maisons Vill'Âge". Les premières résidences sont en train d'être construite dans les deux départements d'Alsace en France. Un appartement a été entièrement équipé pour agir comme laboratoire de recherche et de développement

Matching an oscillator model to a phase response curve

peer reviewedThe Phase Response Curve (PRC) has proven a useful tool for the reduction of complex oscillator models. It is also an information often experimentally available to the biologist. This paper introduces a numerical tool based on the sensitivity analysis of the PRC to adapt initial model parameters in order to match a particular PRC shape. We illustrate the approach on a simple biochemical model of circadian oscillator

Controlling the phase of an oscillator: a phase response curve approach

peer reviewedThe paper discusses elementary control strategies to control the phase of an oscillator. Both feedforward and feedback (P and PI) control laws are designed based on the phase response curve (PRC) calculated from the linearized model. The performance is evaluated on a popular model of circadian oscillations

Étude des liens entre paléogéographie, climat et biodiversité aux échelles de temps géologiques. Apports et questions de la modélisation des paléoclimats

My research work consists of trying to improve our knowledge of the links between the physical world and biodiversity on a geological time scale. I seek both to understand the mechanisms behind the major climate changes of the last 100 million years and to quantify their consequences on the development of biodiversity as we know it today. My presentation will initially focus on the links between palaeogeography and climate. The uplift of mountain ranges, the opening/closing of sea passages, and the break-up of supercontinents are all processes that have altered the climate system (oceanic and atmospheric dynamics in particular) over time. I will show, notably through the thesis work that I had the privilege of co-supervising, how the use of numerical climate models can (i) help to understand and quantify these processes and (ii) benefit to and from paleoclimate proxies, notably isotopic ones. By briefly presenting the development of a low-resolution version of the Earth system model of the Pierre Simon Laplace Institute (IPSL-CM5A2), I will also discuss the limits of these models for studying ancient climates, and will try to discuss their necessary evolution. Finally, I will outline my research project for the coming years, in particular the question of the bridge between geosciences and the problems of macro-evolution of biodiversity. In particular, I will look at methods of integrating spatialised paleoclimatic information into models of diversification of living organisms and how to take into account the feedback of biological evolution on climate.Mon travail de recherche consiste à tenter d’améliorer notre connaissance des liens entre le monde physique et la biodiversité à l’échelle des temps géologiques. Je cherche à la fois à comprendre et spatialiser les mécanismes à l’origine des grands changements climatiques des 100 derniers millions d’années, et à quantifier leurs conséquences sur la mise en place de la biodiversité telle que nous la connaissons aujourd’hui. Mon exposé se concentrera dans un premier temps sur les liens entre paléogéographie et climat. La surrection de chaînes de montagne, l’ouverture/fermeture de passages maritimes, et le fractionnement de supercontinents sont autant de processus qui ont altéré le système climatique (dynamiques océaniques et atmosphériques notamment) au cours du temps. Je montrerai, notamment via les travaux de thèse que j’ai eu la chance de co-encadrer, comment l’utilisation de modèles numériques de climat peut aider à (i) comprendre et quantifier ces processus et (ii) nourrir un aller-retour entre avec les proxies des paléoclimats, notamment isotopiques, en vue de leur interprétation et de l’amélioration des modèles. En présentant brièvement la mise en place d’une version à basse résolution du modèle système Terre de l’Institut Pierre Simon Laplace (IPSL-CM5A2), j’aborderai également les limites de l’utilisation de ces modèles pour les problématiques des climats anciens, et tenterai de discuter de leur nécessaire évolution. Enfin, je déclinerai mon projet de recherche pour les années à venir, notamment la question du pont entre les géosciences et les problématiques de macro-évolution de la biodiversité. Il s’agira notamment de s’interroger sur les méthodes d’intégration d’une information paléoclimatique spatialisée dans les modèles de diversification du vivant ,et de comment prendre en compte la rétroaction de l’évolution biologique sur le climat