Modélisation de l’effet d’une taxe sur la construction : le Versement pour Sous-Densité

National audienceLe Versement pour Sous Densité est une mesure innovante qui a fait son entrée dans la loi française depuis mi-2012 et qui vise à limiter l’étalement urbain en taxant les nouvelles constructions qui n’atteignent pas un Seuil minimal de densité. Ce papier, à travers l’utilisation d’un modèle transportusage des sols (NEDUM 2D), quantifie les impacts potentiels de cette politique sur l’Ile-de-France et examine les conditions qui lui permettraient de gagner en efficacité tout en limitant les coûts sociaux de sa mise en œuvre. Les résultats de cette étude montrent que si cet outil est correctement utilisé, il peut contribuer à limiter l’étalement urbain tout en augmentant les surfaces construites et donc en diminuant le niveau des prix immobiliers et des loyers. De façon surprenante, il s’agit donc d’une taxe sur la construction qui a pour résultat un accroissement des surfaces des logements. Cependant la mise en œuvre de cette politique est compliquée puisque le choix du Seuil minimal de densité en conditionne largement l’efficacité. Si celui-ci est trop bas le versement peut avoir des impacts contre-productifs comme une accélération de l’étalement urbain. De plus, en fonction de l’objectif privilégié (limitation de l’étalement urbain, accès aux transports en commun, …), le choix du seuil optimal variera

Carbon Price Efficiency Lock-in and Path Dependence in Urban Forms and Transport Infrastructure

International audienceThis paper investigates the effect of carbon or gasoline taxes on commuting-related CO2 emissions in an urban context. To assess the impact of public transport on the efficiency of the tax, the paper investigates two exogenous scenarios using a dynamic urban model (NEDUM-2D) calibrated for the urban area of Paris: (i) a scenario with the current dense public transport infrastructure, and (ii) a scenario without. It is shown that the price elasticity of CO2 emissions is twice as high in the short run if public transport options exist. Reducing commuting-related emissions thus requires lower (and more acceptable) tax levels in the presence of dense public transportation. The emission elasticity also depends on the baseline scenario (especially population and income growth) and increases over time. In the longer run, elasticities are similar in the scenarios with and without public transport, due to larger urban reconfiguration in the latter scenario. This analysis may help calibrate general equilibrium models by providing price elasticities that depend on socio-economic and public transport infrastructure scenarios. If the goal of a carbon or gasoline tax is to change behaviors and reduce energy consumption and CO2 emissions (not to raise revenues), then there is an incentive to increase the price elasticity through complementary policies such as innovation support and infrastructure development

CoBaltDB: Complete bacterial and archaeal orfeomes subcellular localization database and associated resources

International audienceBACKGROUND: The functions of proteins are strongly related to their localization in cell compartments (for example the cytoplasm or membranes) but the experimental determination of the sub-cellular localization of proteomes is laborious and expensive. A fast and low-cost alternative approach is in silico prediction, based on features of the protein primary sequences. However, biologists are confronted with a very large number of computational tools that use different methods that address various localization features with diverse specificities and sensitivities. As a result, exploiting these computer resources to predict protein localization accurately involves querying all tools and comparing every prediction output; this is a painstaking task. Therefore, we developed a comprehensive database, called CoBaltDB, that gathers all prediction outputs concerning complete prokaryotic proteomes. DESCRIPTION: The current version of CoBaltDB integrates the results of 43 localization predictors for 784 complete bacterial and archaeal proteomes (2.548.292 proteins in total). CoBaltDB supplies a simple user-friendly interface for retrieving and exploring relevant information about predicted features (such as signal peptide cleavage sites and transmembrane segments). Data are organized into three work-sets ("specialized tools", "meta-tools" and "additional tools"). The database can be queried using the organism name, a locus tag or a list of locus tags and may be browsed using numerous graphical and text displays. CONCLUSIONS: With its new functionalities, CoBaltDB is a novel powerful platform that provides easy access to the results of multiple localization tools and support for predicting prokaryotic protein localizations with higher confidence than previously possible. CoBaltDB is available at http://www.umr6026.univ-rennes1.fr/english/home/research/basic/software/cobalten

An iterative procedure for differential analysis of gene expression

Microarrays are a popular technology to study genes that are differentially expressed between two conditions. In this Note, we propose an iterative procedure to determine the biggest subset of non-differentially expressed genes. We prove a pseudo Markov relationship that allows practical computations. We obtain explicit expressions for FDR and the level of the proposed test at each step. To cite this article: A. Bar-Hen, S. Robin, C. R. Acad. Sci. Paris, Ser. I ••• (••••)

OxyGene: an innovative platform for investigating oxidative-response genes in whole prokaryotic genomes

International audienceBACKGROUND: Oxidative stress is a common stress encountered by living organisms and is due to an imbalance between intracellular reactive oxygen and nitrogen species (ROS, RNS) and cellular antioxidant defence. To defend themselves against ROS/RNS, bacteria possess a subsystem of detoxification enzymes, which are classified with regard to their substrates. To identify such enzymes in prokaryotic genomes, different approaches based on similarity, enzyme profiles or patterns exist. Unfortunately, several problems persist in the annotation, classification and naming of these enzymes due mainly to some erroneous entries in databases, mistake propagation, absence of updating and disparity in function description. DESCRIPTION: In order to improve the current annotation of oxidative stress subsystems, an innovative platform named OxyGene has been developed. It integrates an original database called OxyDB, holding thoroughly tested anchor-based signatures associated to subfamilies of oxidative stress enzymes, and a new anchor-driven annotator, for ab initio detection of ROS/RNS response genes. All complete Bacterial and Archaeal genomes have been re-annotated, and the results stored in the OxyGene repository can be interrogated via a Graphical User Interface. CONCLUSION: OxyGene enables the exploration and comparative analysis of enzymes belonging to 37 detoxification subclasses in 664 microbial genomes. It proposes a new classification that improves both the ontology and the annotation of the detoxification subsystems in prokaryotic whole genomes, while discovering new ORFs and attributing precise function to hypothetical annotated proteins. OxyGene is freely available at: http://www.umr6026.univ-rennes1.fr/english/home/research/basic/software

Interplay between transcription regulators RUNX1 and FUBP1 activates an enhancer of the oncogene c-KIT and amplifies cell proliferation.

Runt-related transcription factor 1 (RUNX1) is a well-known master regulator of hematopoietic lineages but its mechanisms of action are still not fully understood. Here, we found that RUNX1 localizes on active chromatin together with Far Upstream Binding Protein 1 (FUBP1) in human B-cell precursor lymphoblasts, and that both factors interact in the same transcriptional regulatory complex. RUNX1 and FUBP1 chromatin localization identified c-KIT as a common target gene. We characterized two regulatory regions, at +700 bp and +30 kb within the first intron of c-KIT, bound by both RUNX1 and FUBP1, and that present active histone marks. Based on these regions, we proposed a novel FUBP1 FUSE-like DNA-binding sequence on the +30 kb enhancer. We demonstrated that FUBP1 and RUNX1 cooperate for the regulation of the expression of the oncogene c-KIT. Notably, upregulation of c-KIT expression by FUBP1 and RUNX1 promotes cell proliferation and renders cells more resistant to the c-KIT inhibitor imatinib mesylate, a common therapeutic drug. These results reveal a new mechanism of action of RUNX1 that implicates FUBP1, as a facilitator, to trigger transcriptional regulation of c-KIT and to regulate cell proliferation. Deregulation of this regulatory mechanism may explain some oncogenic function of RUNX1 and FUBP1

ETV6-RUNX1 and RUNX1 directly regulate RAG1 expression: one more step in the understanding of childhood B-cell acute lymphoblastic leukemia leukemogenesis.

Funder: Société Française de Biochimie et Biologie Moléculaire ; French Research MinistryFunder: Cancéropole Grand Ouest ; Région Bretagne ; Société Française d’HématologieFunder: Ligue Régionale contre le cancer ;ETV6-RUNX1 and RUNX1 directly promote RAG1 expression. ETV6-RUNX1 and RUNX1 preferentially bind to the −1200 bp enhancer of RAG1 and the −80 bp promoter of RAG1 gene respectively, and compete for these bindings. ETV6-RUNX1 and RUNX1 induce an excessive RAG recombinase activity. ETV6-RUNX1 participates directly in two events of the multi-hit ALL leukemogenesis: as an initiating event and as an activator of RAG1 expression

Reduction of RUNX1 transcription factor activity by a CBFA2T3-mimicking peptide: application to B cell precursor acute lymphoblastic leukemia.

Funder: FP7 People: Marie-Curie Actions; doi: http://dx.doi.org/10.13039/100011264; Grant(s): 291851BACKGROUND: B Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) is the most common pediatric cancer. Identifying key players involved in proliferation of BCP-ALL cells is crucial to propose new therapeutic targets. Runt Related Transcription Factor 1 (RUNX1) and Core-Binding Factor Runt Domain Alpha Subunit 2 Translocated To 3 (CBFA2T3, ETO2, MTG16) are master regulators of hematopoiesis and are implicated in leukemia. METHODS: We worked with BCP-ALL mononuclear bone marrow patients' cells and BCP-ALL cell lines, and performed Chromatin Immunoprecipitations followed by Sequencing (ChIP-Seq), co-immunoprecipitations (co-IP), proximity ligation assays (PLA), luciferase reporter assays and mouse xenograft models. RESULTS: We demonstrated that CBFA2T3 transcript levels correlate with RUNX1 expression in the pediatric t(12;21) ETV6-RUNX1 BCP-ALL. By ChIP-Seq in BCP-ALL patients' cells and cell lines, we found that RUNX1 is recruited on its promoter and on an enhancer of CBFA2T3 located - 2 kb upstream CBFA2T3 promoter and that, subsequently, the transcription factor RUNX1 drives both RUNX1 and CBFA2T3 expression. We demonstrated that, mechanistically, RUNX1 and CBFA2T3 can be part of the same complex allowing CBFA2T3 to strongly potentiate the activity of the transcription factor RUNX1. Finally, we characterized a CBFA2T3-mimicking peptide that inhibits the interaction between RUNX1 and CBFA2T3, abrogating the activity of this transcription complex and reducing BCP-ALL lymphoblast proliferation. CONCLUSIONS: Altogether, our findings reveal a novel and important activation loop between the transcription regulator CBFA2T3 and the transcription factor RUNX1 that promotes BCP-ALL proliferation, supporting the development of an innovative therapeutic approach based on the NHR2 subdomain of CBFA2T3 protein

Aircraft Numerical "Twin": A Time Series Regression Competition

International audienceThis paper presents the design and analysis of a data science competition on a problem of time series regression from aeronautics data. For the purpose of performing predictive maintenance, aviation companies seek to create aircraft "numerical twins", which are programs capable of accurately predicting strains at strategic positions in various body parts of the aircraft. Given a number of input parameters (sensor data) recorded in sequence during the flight, the competition participants had to predict output values (gauges), also recorded sequentially during test flights, but not recorded during regular flights. The competition data included hundreds of complete flights. It was a code submission competition with complete blind testing of algorithms. The results indicate that such a problem can be effectively solved with gradient boosted trees, after preprocessing and feature engineering. Deep learning methods did not prove as efficient

Conceiving Particles as Undulating Granular Systems Allows Fundamentally Realist Interpretation of Quantum Mechanics

International audienceThe strange behavior of subatomic particles is described by quantum theory, whose standard interpretation rejected some fundamental principles of classical physics such as causality, objectivity, locality, realism and determinism. Recently, a granular relativistic electrodynamical model of the electron could capture the measured values of its observables and predict its mass from the stability of its substructure. The model involves numerous subparticles that constitute some tight nucleus and loosely bound envelope allegedly forming real waves. The present study examines whether such a substructure and associated dynamics allow fundamentally realist interpretations of emblematic quantum phenomena, properties and principles, such as wave-particle duality, loss of objectivity, quantization, simultaneous multipath exploration, collapse of wavepacket, measurement problem, and entanglement. Drawing inspiration from non-linear dynamical systems, subparticles would involve realist hidden variables while high-level observables would not generally be determined, as particles would generally be in unstable states before measurements. Quantum mechanics would constitute a high-level probabilistic description emerging from an underlying causal, objective, local, albeit contextual and unpredictable reality. Altogether, by conceiving particles as granular systems composed of numerous extremely sensitive fluctuating subcorpuscles, this study proposes the possible existence of a local fundamentally realist interpretation of quantum mechanics