Synthetic mammalian trigger-controlled bipartite transcription factors

Synthetic biology has significantly advanced the design of synthetic control devices, gene circuits and networks that can reprogram mammalian cells in a trigger-inducible manner. Prokaryotic helix-turn-helix motifs have become the standard resource to design synthetic mammalian transcription factors that tune chimeric promoters in a small molecule-responsive manner. We have identified a family of Actinomycetes transcriptional repressor proteins showing a tandem TetR-family signature and have used a synthetic biology-inspired approach to reveal the potential control dynamics of these bi-partite regulators. Daisy-chain assembly of well-characterized prokaryotic repressor proteins such as TetR, ScbR, TtgR or VanR and fusion to either the Herpes simplex transactivation domain VP16 or the Krueppel-associated box domain (KRAB) of the human kox-1 gene resulted in synthetic bi- and even tri-partite mammalian transcription factors that could reversibly program their individual chimeric or hybrid promoters for trigger-adjustable transgene expression using tetracycline (TET), γ-butyrolactones, phloretin and vanillic acid. Detailed characterization of the bi-partite ScbR-TetR-VP16 (ST-TA) transcription factor revealed independent control of TET- and γ-butyrolactone-responsive promoters at high and double-pole double-throw (DPDT) relay switch qualities at low intracellular concentrations. Similar to electromagnetically operated mechanical DPDT relay switches that control two electric circuits by a fully isolated low-power signal, TET programs ST-TA to progressively switch from TetR-specific promoter-driven expression of transgene one to ScbR-specific promoter-driven transcription of transgene two while ST-TA flips back to exclusive transgene 1 expression in the absence of the trigger antibiotic. We suggest that natural repressors and activators with tandem TetR-family signatures may also provide independent as well as DPDT-mediated control of two sets of transgenes in bacteria, and that their synthetic transcription-factor analogs may enable the design of compact therapeutic gene circuits for gene and cell-based therapie

Adaptive Optics Feedback Control

This book is a collection of 19 articles which reflect the courses given at the Collège de France/Summer school “Reconstruction d'images − Applications astrophysiques“ held in Nice and Fréjus, France, from June 18 to 22, 2012. The articles presented in this volume address emerging concepts and methods that are useful in the complex process of improving our knowledge of the celestial objects, including Earth

Engagement économique et préoccupations socio-environnementales dans l’achat « Made in France »

International audienceThe purpose of this article is to study the role of the consumer's economic commitment in the building of preferences. Economic aspect can’t to be disconnected from other societal concerns. It is modeled alongside the socio- environmental concerns. To understand this role, an experiment with the use of the conjoint analysis is carried out on a representative sample of 596 respondents. The main results show that economic commitment significantly increases the utility of domestic origin and the utility of quality.L’objectif de cet article consiste à étudier le rôle de l’engagement économique du consommateur dans la formation de ses préférences. Ne pouvant être déconnectée des autres préoccupations sociétales, les dimensions économique est modélisée aux cotés des préoccupations socio-environnementales. Pour comprendre ce rôle, une expérimentation avec l’utilisation de l’analyse des mesures conjointes est réalisée sur un échantillon représentatif de 596 répondants. Les principaux résultats démontrent que l’engagement économique accroit significativement l’utilité partielle de l’origine domestique du produit et diminue celle qu’il accorde à la qualité du produit

A Spatial-based KDD Process to Better Understand the Spatiotemporal Phenomena

International audienceIn this paper, we present a knowledge discovery process ap- plied to hydrological data. To achieve this objective, we combine succes- sive methods to extract knowledge on data collected at stations located along several rivers. Firstly, data is pre processed in order to obtain different spatial proximities. Later, we apply two algorithms to extract spatiotemporal patterns and compare them. Such elements can be used to assess spatialized indicators to assist the interpretation of ecological and rivers monitoring pressure data

Bt maize: a tool for improving food safety of grains at harvest

A new EU (European Union) regulation came into force in 2007 with Regulation (EC) No. 1126/2007 which established maximum levels for fumonisins B1 and B2 (4000 ppb), deoxynivalenol (1750 ppb) and zearalenone (350 ppb) in maize and maize products. In order to evaluate French maize food safety, studies were carried out by the national Biological Risk Monitoring (BRM) Network. In this study, field trials involving 84 plots were conducted with Bt maize (MON 810) and its isogenic non-Bt counterpart in 2005 and 2006 in South-western France. Mycotoxin levels were determined in grain at harvest. Fumonisins B1 and B2, deoxynivalenol, and zearalenone were analyzed by LC-MS-MS and the results treated statistically using non parametric tests for mycotoxins and analysis of variance test for weather variables. As the climate was homogenous inside the experimental area, the transgenic event introduced into the maize was the only key parameter which differed between Bt and non-Bt maize plots. Our results showed that all mycotoxin families were not impacted in the same way. The efficacy of Bt maize reduced mycotoxins more than 90% for fumonisins and more than 50% for zearalenone although deoxynivalenol was lightly increased. Therefore a competition between the different Fusarium spp. which produced fumonisins or trichothecenes is hypothesized. According to Regulation (EC) No. 1126/2007, 93% of the maize of Bt maize plots were able to be commercialized compared to only 45% for non-Bt maize plots. The results of this work showed that Bt maize improved food safety and constituted an useful tool to reduce significantly mycotoxin levels in harvested and stored grains. Keywords: Bt (MON810) maize, Fumonisins B1 and B2, Deoxynivalenol (DON), Zearalenone, EC regulation 1126/2007 threshold

Les instruments transitionnels : une proposition pour étudier la diachronie des activités narratives

Cet article présente les activités narratives de deux expéditeurs polaires. Nous adoptons une unité d’analyse diachronique qui englobe la constitution du recueil lors du voyage ainsi que l’élaboration du récit après le voyage. Dans cette optique, nous articulons théoriquement et méthodologiquement l’approche instrumentale et le cours d’action. Nous proposons le concept d’instrument transitionnel pour désigner ce qui transite au sein de ces activités narratives discontinues. Lors du voyage, les narrateurs opèrent une mise à distance de l’expérience grâce aux activités de recueil instrumentées (prises de notes, de photographies). C’est à ce moment là qu’ils constituent leurs instruments transitionnels. Après le voyage, les narrateurs se ré-imprègnent de l’expérience de voyage grâce à l’étalage des éléments recueillis (croquis, cartes, écrits..). Ils élaborent le récit en assemblant les instruments transitionnels. Pour finir, nous discutons des apports de la diachronie pour mieux étudier et outiller les activités créatives.This paper presents the narrative activity of two polar explorers. We have adopted a unit of diachronic analysis that encompasses the collection procedure during the journey, as well as the drafting of the story afterwards. With this in mind, we focus on two theoretical frameworks : the instrumental approach and the course of action. We suggest using the concept of "transitional instrument" to identify what is occurring within these discontinuous narrative activities. During the journey, the narrators work with various instruments (e.g. photographs, notes) as a way of distancing themselves from the experience. At this stage they create their own transitional instruments. After the journey, the narrators are once again immersed in the travel experience through a display of the items collected, such as sketches, notes and maps. They compose the story by assembling the transitional instruments. We will conclude with a discussion of how diachronicity contributes to a better understanding of creative activities and the related tools