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The cystic fibrosis transmembrane conductance regulator (CFTR) anion channel is essential to maintain fluid homeostasis in key organs such as the lungs or the digestive systems. Functional impairment of CFTR due to mutation in the cftr gene lead to Cystic Fibrosis (CF) the most common lethal genetic disorder. Here we observe that the first nucleotide-binding domain (NBD1) of CFTR can spontaneously adopt an alternative conformation that departs from the canonical NBD fold previously observed for CFTR and other ATP-binding cassette (ABC) transporter proteins. Crystallography studies reveal that this conformation involves a topological reorganization of the β-subdomain of NBD1. This alternative state is adopted by wild-type CFTR in cells, where it leads to enhanced channel activity. Single-molecule fluorescence resonance energy transfer microscopy shows that the equilibrium between the conformations is regulated by ATP binding. However, under destabilizing conditions, such as a the prominent disease-causing mutation F508el , this conformational flexibility enables unfolding of the β-subdomain. Our data indicate that in wild-type CFTR switching to this topologically-swapped conformation of NBD1 regulates channel function, but, in the presence of the F508del mutation, it allows domain misfolding and subsequent protein degradation. Our work provides a framework to design conformation-specific therapeutics to prevent noxious transitions.

National audience; The analysis and mapping of agronomic and environmental spatial data require observations to be comparable. Heterogeneous spatial datasets are those for which the observations of different datasets cannot be directly compared because they have not been collected under the same set of acquisition conditions, for instance within the same time period (if the variable of interest varies across time), with consistent sensors or under similar management practices (if the management practices impact the measured value) among others. When heterogeneous acquisition conditions take place, there is a need for harmonization procedures to make possible the comparison of such observations. This analysis details and compares four automated methodologies that could be used to harmonize heterogeneous spatial agricultural datasets so that the data can be analysed and mapped conjointly. The theory and derivation of each approach, including a novel, local spatial approach is given. These methods aim to minimize the occurrence of discrepancies (discontinuities) in the data. The four approaches were evaluated and compared with a sensitivity analysis on simulated datasets with known characteristics. Results showed that none of the four methods consistently delivered a better harmonization accuracy. The accuracy and preferred choice for the harmonization procedures was shown to be influenced by (i) within-field spatial structures of the datasets, (ii) differences in acquisition conditions between the heterogeneous spatial datasets, and (iii) the spatial resolution of the simulated data. The four approaches were used to harmonize real within-field grain yield datasets and a discussion to help users select an appropriate harmonization methodology proposed. Despite significant improvements in dataset harmonization, discontinuities were not entirely removed and some uncertainty remained.

Arithmetic facts (AFs) are required when solving problems such as “3 × 4” and refer to calculations for which the correct answer is retrieved from memory. Currently, two important effects that modulate the performance in AFs have been highlighted: the problem size effect and the proactive interference effect. The aim of this study is to investigate possible age-related changes of the problem size effect and the proactive interference effect in AF solving. To this end, the performance of young and older adults was compared in a multiplication production task. Furthermore, an independent measure of proactive interference was assessed to further define the architecture underlying this effect in multiplication solving. The results indicate that both young and older adults were sensitive to the effects of interference and of the problem size. That is, both interference and problem size affected performance negatively: the time needed to solve a multiplication problem increases as the level of interference and the size of the problem increase. Regarding the effect of ageing, the problem size effect remains constant with age, indicating a preserved AF network in older adults. Interestingly, sensitivity to proactive interference in multiplication solving was less pronounced in older than in younger adults suggesting that part of the proactive interference has been overcome with age., SCOPUS: ar.j, info:eu-repo/semantics/published

International audience; Satellite-derived products are of key importance for the high-resolution monitoring of the ocean surface on a global scale. Due to the sensitivity of spaceborne sensors to the atmospheric conditions as well as the associated spatio-temporal sampling, ocean remote sensing data may be subject to high-missing data rates. The spatio-temporal interpolation of these data remains a key challenge to deliver L4 gridded products to end-users. Whereas operational products mostly rely on model-driven approaches, especially optimal interpolation based on Gaussian process priors, the availability of large-scale observation and simulation datasets calls for the development of novel data-driven models. This study investigates such models. We extend the recently introduced analog data assimilation to high-dimensional spatio-temporal fields using a multi-scale patch-based decomposition. Using an Observing System Simulation Experiment (OSSE) for sea surface temperature, we demonstrate the relevance of the proposed data-driven scheme for the real missing data patterns of the high-resolution infrared METOP sensor. It has resulted in a significant improvement w.r.t. state-of-the-art techniques in terms of interpolation error (about 50\% of relative gain) and spectral characteristics for horizontal scales smaller than 100km. We further discuss the key features and parameterizations of the proposed data-driven approach as well as its relevance with respect to classical interpolation techniques.

We extend the optimum safety factor method to nonlinear probabilistic distributions.We apply the developed formulations on shank chisel plough design.We show the advantage of our probabilistic method relative to the deterministic one. Reliability integration into tillage machine design process is a new strategy to overcome the drawbacks of classical design approaches and to achieve designs with a required reliability level. Furthermore, design optimization of soil tillage equipments under uncertainty seeks to design structures which should be both economic and reliable. The originality of this research is to develop an efficient methodology that controls the reliability levels for complex statistical distribution cases of random tillage forces. This developed strategy is based on design sensitivity concepts in order to determine the influence of each random parameter. The application of this method consists in taking into account the uncertainties on the soil tillage forces. The tillage forces are calculated in accordance with analytical model of McKyes and Ali with some modifications to include the effect of both soil-metal adhesion and tool speed. The different developments and applications show the importance of the developed method to improve the performance of the soil tillage equipments considering both random geometry and loading parameters. The developed method so-called OSF (Optimum Safety Factor) can satisfy a required reliability level without additional computing time relative to the deterministic design optimization study. Since the agricultural equipment parameters are extremely nonlinear, we extended the OSF approach to several nonlinear probabilistic distributions such as lognormal, uniform, Weibull and Gumbel probabilistic distribution laws.

Inventories of extreme floods ar ungauged sites and regional flood frequency analyses: methodological reflexions. This paper presents additional developments about a flood frequency approach proposed by Gaume [2010], that aimed to incorporate available information on extreme floods at ungauged sites in a regional flood frequency analysis. Extreme floods, indeed, may represent a very large additional record length if compared with gauged series, and therefore may highly improve the accuracy of flood quantiles estimates. However, the proposed approach requires to calibrate an index flood relationship (here an exponent of catchment surface), which represents a complement of parametrisation of the regional statistical model. The performances and robustness of this approach are tested here and compared to the conventional regionalisation approach of Hosking [ 1997]. The comparison is based both on simulations and on a case study. The inference procedure used is based on a GEV distribution associated with a specific likelihood formulation and a Bayesian MCMC approach for parameters estimation. The parameters of the index flood relationship and the GEV distribution are all calibrated in the same time using the MCMC algorithm, and therefore the uncertainty associated with the index flood relationship calibration is taken into account. The inference results obtained without incorporation of extreme events are first compared, with focus on the effects of the index flood relationship estimation and on the presence of heterogeneities around this relationship. This first comparison is based on simulations and illustrates some limitations of both of the methods : sensitivity to the length of local series in the case of the Hosking approach, presence of bias for small catchment surfaces and relative sensitivity to heterogeneities in the case of the proposed approach. As far as the available information is limited to gauged series and if heterogeneity remains limited, the two approaches finally show similar performances. The two approaches are then applied to a case study : the Ardèche region in south east of France (168 gauged records at 5 sites and 19 ungauged extremes). This application confirms the very positive effect of the information on extreme floods, that clearly enables to outperform the results based only on gauged series., Cet article présente des développements et une évaluation de l’approche d’analyse régionale des débits proposée par Gaume [ 2010], consistant à incorporer dans l’analyse régionale les informations relatives aux crues extrêmes observées sur des bassins non jaugés. L’information sur les crues extrêmes s’apparente en effet à une longue durée d’enregistrements supplémentaires qui est susceptible d’améliorer grandement l’estimation des quantiles de crue. Toutefois, cette approche nécessite de calibrer une relation d’index de crue (ici un exposant de la surface du bassin versant), ce qui représente un complément de paramétrisation du modèle régional utilisé. Une évaluation des performances et de la robustesse de la méthode sont proposées ici par comparaison à une approche régionale plus classique proposée par Hosking [ 1997]. La procédure d’inférence utilisée s’appuie sur une distribution GEV, associée à une formulation spécifique de la vraisemblance et une approche Bayésienne MCMC pour l’estimation des paramètres. Les paramètres de la relation d’index de crue et de la distribution GEV sont évalués ici conjointement au sein de l’algorithme MCMC, ce qui permet de tenir compte de l’incertitude associée à l’ajustement de la relation d’index de crue. Dans un premier temps, les performances des deux méthodes sont comparées à partir de simulations, sans utiliser d’informations sur les crues extrêmes. La sensibilité aux hétérogénéités autour de la relation d’index de crue est notamment examinée. Dans un deuxième temps, les deux approches sont appliquées à une étude de cas : la région de l’Ardèche (168 années stations sur 5 site et 19 crues extrêmes sur sites non jaugés)., N’guyen Chi Cong, Payrastre Olivier Renaud, Gaume Eric. Inventaires de crues extrêmes sur des sites non jaugés et analyse statistique régionale des débits: réflexions méthodologiques et évaluation des performances. In: Evénements extrêmes fluviaux et maritimes. Leurs variabilités spatiales et chronologiques dans l'ouest de l’Europe. 34èmes journées de l’hydraulique Paris, 1 et 2 février 2012. 2012.

Sensitivity of Chaos to External Conditions: Using the example provided by Guy Tchibozo in the BMS (n. 74, 2002), the author uses simulation methods to study the results of various initial conditions for the model, showing the the results can be chaotic or stable depending to specific parameters. En employant l’exemple fournit by Guy Tchibozo dans le BMS (n. 74, 2002), l’auteur utilise des méthodes de simulation pour étudier les résultats de diverses conditions initiales pour le modèle étudié, montrant que les résultats peuvent être chaotiques ou stables en relation avec le choix de certains paramètres.

Modal active control, based on a state model, is an efficient method of increasing the lifetime of electronic boards by using piezoelectric components. In the case of industrial mass production, dispersions lead to changes in mechanical and electromechanical properties. Moreover, initial operating conditions such as boundary conditions can change during the lifetime of the control and modify its efficiency and stability. Therefore, a semi-adaptive modal control strategy in deferred time is proposed to attenuate these problems. Firstly modal control gains are calculated by using a classical linear quadratic Gaussian algorithm with the nominal model including mode shapes. Then control I/O data are collected by an identification system that uses on-board piezoelectric components. A subspace method is implemented to estimate modal matrices in order to update the controller. The sensitivity of control performance to modal parameter variation is presented. Estimated control frequencies and modal damping are finally used to update modal control gains. The effectiveness of the proposed method is examined through numerical simulation and experimental tests in the case of boundary condition modifications. This adaptive modal control/identification design greatly increases the nominal robustness of the controller in the case of frequency shifts.

The work presented in this article is focussed on the design of robust Fault Detection and Isolation (FDI) filters for the class of LPV (Linear Parameter Varying) systems. A sufficient condition is established to guarantee sensitivity performances of the residual signal vector to faults. Robustness constraints against model perturbations and disturbances are also taken into account in the design method. The synthesis problem is formulated in terms of a convex optimization problem which is solved using LMI (Linear Matrix Inequalities) techniques. The proposed method is applied to the secondary circuit of a Nuclear Power Plant.

National audience; We describe a matter-wave cavity based gravimeter closed on one end by periodic Gaussian Raman pulses. The gravimeter sensitivity increases quickly with the number of cycles experienced by the condensate inside the cavity. The matter wave is refocused thanks to a spherical wavefront for the Raman pulses. This technique opens the way to experimental realizations of controllable atom optics devices such as condensate lenses or convergent mirrors.

A model of pitch perception is presented involving an array of delay lines and inhibitory gating neurons. In response to a periodic sound, a minimum appears in the pattern of outputs of the inhibitory neurons at a lag equal to the period of the sound. The position of this minimum is the cue to pitch. The model is similar to the autocorrelation model of pitch, multiplication being replaced by an operation similar to subtraction, and maxima by minima. The two models account for a wide class of pitch phenomena in very much the same way. The principal goal of this paper is to demonstrate this fact. Several features of the cancellation model may be to its advantage: it is closely related to the operation of harmonic cancellation that can account for segregation of concurrent harmonic stimuli, it can be generalized to explain the perception of multiple pitches, and it shows a greater degree of sensitivity to phase than autocorrelation, which may allow it to explain certain phenomena that autocorrelation cannot account for.

International audience

The cross-axis sensitivity of accelerometers that is of the order of a few hundredths of the main axis sensitivity, is a common concern in vibration measurements. Usually the manufacturers do not provide a complete information upon the transverse sensitivity of transducers. The transverse motion of mechanical shakers is subject to the the problem and lack of information. The method that we present here is aimed at calibrating at the same time both defaults relatively to the axial components. By mounting an accelerometer on a shaker so that the main motion is perpendicular to the main sensitivity, its response adds up two products of the same order of magnitude: the main motion x the cross-axis sensitivity and the main sensitivity x the transverse motion. These two quantities are separated when the accelerometer rotates around the main-motion axis. All relative components of transverse motion and cross-axis sensitivity are derived from a combination of orientations of the accelerometer relatively to the main-motion axis. Measurements made with a variety of accelerometers exhibit a good consistency of the results concerning the transverse motion of a given shaker. Conversely, a good reproducibility of results pertaining to the cross-axis sensitivity of accelerometers has been achieved. The range in which that method is easily used with good results is limited in the low-frequency region by the motion of the shaker base and attachment