Accessing ns–μs side chain dynamics in ubiquitin with methyl RDCs

This study presents the first application of the model-free analysis (MFA) (Meiler in J Am Chem Soc 123:6098–6107, 2001; Lakomek in J Biomol NMR 34:101–115, 2006) to methyl group RDCs measured in 13 different alignment media in order to describe their supra-τc dynamics in ubiquitin. Our results indicate that methyl groups vary from rigid to very mobile with good correlation to residue type, distance to backbone and solvent exposure, and that considerable additional dynamics are effective at rates slower than the correlation time τc. In fact, the average amplitude of motion expressed in terms of order parameters S2 associated with the supra-τc window brings evidence to the existence of fluctuations contributing as much additional mobility as those already present in the faster ps-ns time scale measured from relaxation data. Comparison to previous results on ubiquitin demonstrates that the RDC-derived order parameters are dominated both by rotameric interconversions and faster libration-type motions around equilibrium positions. They match best with those derived from a combined J-coupling and residual dipolar coupling approach (Chou in J Am Chem Soc 125:8959–8966, 2003) taking backbone motion into account. In order to appreciate the dynamic scale of side chains over the entire protein, the methyl group order parameters are compared to existing dynamic ensembles of ubiquitin. Of those recently published, the broadest one, namely the EROS ensemble (Lange in Science 320:1471–1475, 2008), fits the collection of methyl group order parameters presented here best. Last, we used the MFA-derived averaged spherical harmonics to perform highly-parameterized rotameric searches of the side chains conformation and find expanded rotamer distributions with excellent fit to our data. These rotamer distributions suggest the presence of concerted motions along the side chains

Conformational Investigations in Flexible Molecules Using Orientational NMR Constraints in Combination with 3J-Couplings and NOE Distances

The downscaling of NMR tensorial interactions, such as dipolar couplings, from tens of kilohertz to a few hertz in low-order media is the result of dynamics spanning several orders of magnitudes, including vibrational modes (~ns-fs), whole-molecule reorientation (~ns) and higher barrier internal conformational exchange (<ms). In this work, we propose to employ these dynamically averaged interactions to drive an “alignment-tensor-free” molecular dynamic simulation with orientation constraints (MDOC) in order to efficiently access the conformational space sampled by flexible small molecules such as natural products. Key to this approach is the application of tensorial pseudo-force restraints which simultaneously guide the overall reorientation and conformational fluctuations based on defined memory function over the running trajectory. With the molecular mechanics force-field, which includes bond polarization theory (BPT), and complemented with other available NMR parameters such as NOEs and scalar J-couplings, MDOC efficiently arrives at dynamic ensembles that reproduce the entire NMR dataset with exquisite accuracy and theoretically reveal the systems conformational space and equilibrium. The method as well as its potential towards configurational elucidation is presented on diastereomeric pairs of flexible molecules: a small 1,4-diketone 1 with a single rotatable bond as well as a 24-ring macrolide related to the natural product mandelalide A 2

Etude rétrospective sur 3 mois de la prise en charge des épistaxis aux urgences du CHU de Clermont-Ferrand et analyse à un mois des récidives précoces

Les épistaxis récurrentes représentent la plus fréquente des urgences ORL. En effet 60% de la population générale aurait déjà souffert d'une épistaxis au moins une fois dans leur vie. Paradoxalement 5 à 10% d'entre elles nécessitent une prise en charge médicale et seulement 0,5 à 1% des épistaxis seront prises en charge par un oto-rhino-laryngologiste. De nombreuses études ont démontrés que plus de 80% de toutes les épistaxis proviendraient de la région antérieure du septum nasal au niveau du plexus de Kiesselbach, zone facilement accessible à une thérapeutique non invasive. Quand est-il du suivi des patients ayant bénéficiés d'un traitement de leur épistaxis au CHRU de Clermont-Ferrand ? Nous avons effectué une étude rétrospective monocentrique observationnelle, sur une période de 3 mois avec suivi d'une cohorte de 59 patients sur un mois. Nous avons ensuite recontacté ces patients, un mois après leur passage aux urgences (représentant la période propice aux récidives précoces), pour noter la survenue d'une récidive durant cette période. L'analyse statistique des données s'est faite par comparaison de 2 sous groupes (l'un présentant une récidive précoce et l'autre non). Pratiquement la moitié des patients ont un traitement modifiant la coagulation sanguine. Le méchage antérieur est majoritairement réalisé par un méchage de type Merocel® dans notre service des urgences. L'antibiothérapie préventive, utilisée lors d'un méchage antérieur, ne représente que 61% des patients méchés. Le taux de récidive précoce est de 30% et le pourcentage de patients méchés consultant un spécialiste de 36%. Notre étude trouve ses limites statistiques dans le nombre de perdus de vues probablement trop important puisqu'il atteint 20%. Le faible taux de rechute à un mois peut s'expliquer par l'utilisation quasi systématique d'un type de méchage antérieur et par le recours important au spécialiste lors de la phase délicate du déméchage.CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Etude de la prédiction de chocs véhicule-piéton

Cette thèse CIFRE s'intéresse à la " prédiction de chocs véhicule-piéton " au sein d'un dispositif de protection des piétons, de type pré-crash. Les accidents véhicule-piéton ont d'abord été étudiés, afin de disposer d'une base de référence pour l'évaluation, grâce aux simulations, de systèmes intelligents de protection des piétons. Le comportement des piétons a ensuite été étudié, et un modèle statistique, à temps continu, reposant sur quatre états discrets, a été proposé et évalué. Ce modèle de piétons a été utilisé pour réaliser une prédiction probabiliste des chocs véhicule-pie ton. Cette prédiction est réalisée grâce à des simulations de type Monte Carlo. Pour en améliorer l'efficacité, des méthodes de réduction de variance, de type " splitting " et " roulette russe " ont été évaluées. Enfin, diverses hypothèses sur la qualité des mesures, réalisées par le futur dispositif de " détection de piétons et d'estimation de leurs positions et vitesses relatives ", qui sont les entrées du module de prédiction de chocs, ont été évaluées, afin de spécifier le besoin sur un tel dispositif.Ce travail a fait l'objet de trois articles publiés et de cinq brevets.This PhD thesis treats the prediction of vehicle-to-pedestrian accidents as part of a pedestrian precrash protection system. The study began with a thorough evaluation of these accidents. The data obtained from this work were then used to generate reference cases that allow the evaluation of intelligent pedestrian protection systems based on simulations. In the next step, the behavior of pedestrians was studied and a continuous-time statistical model, based on four discrete states, was proposed and evaluated.This pedestrian model makes possible a probabilistic prediction of vehicle-to-pedestrian accidents, for which Monte Carlo simulations were used. Variance reduction methods such as splitting and Russian roulette were used to improve the algorithms' performance. Finally, several hypotheses were proposed with aim of modeling the uncertainties involved in detecting pedestrians and estimating their relative positions and speeds system. Evaluating different types of uncertainties on these measurements, which are the inputs of the prediction module, contributes to the specification of a system that detects pedestrians and estimates their positions and speeds.This work led to three published articles and five patent applications.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Power Allocation for Minimizing Energy Consumption of OFDMA Downlink with Cell DTx

International audienceWith Cell DTx, a base station can dynamically be switched to sleep mode during very short periods (inferior to frame duration) in order to reduce its energy consumption. In this paper, we study the problem of energy consumption minimization with Cell DTx for the downlink of an Orthogonal Frequency Division Multiple Access (OFDMA) base station. We show that this problem can be rewritten as a convex problem. Then, we derive interpretable expressions for the transmit power and sleep mode duration which minimize the energy consumption. Besides, we show that resource allocation algorithms already proposed for transmit power minimization have near optimal performance. Simulation results show that up to 38% of base station energy consumption can be saved with Cell DTx

Power Spectrum density of Single Side band CPM using Lorenztian frequency pulses

International audienceWe propose a new waveform for frequency-shift keying continuous phase modulation (FSK-CPM) that directly generates a single side band (SSB) spectrum. The original principle, inspired from quantum physics (levitons), is presented. From the simple analytical form of the modulation, orthonormal wave-functions and analytical expressions leading to the SSB power spectrum density are proposed. This CPM modulation displays a very compact spectrum, with 99% of the power in the primary bandwidth. Its SSB property makes this FSK-CPM scheme, hereby called SSB-FSK, a promising solution not sensitive to image frequency degradation and would allow large bit rates transmission at low carrier frequency

From Quantum Physics to Digital Communication: Single Side Band Continuous Phase Modulation

International audienceIn the present paper, we propose a new frequency-shift keying continuous phase modulation (FSK-CPM) scheme having, by essence, the interesting feature of single side-band (SSB) spectrum providing a very compact frequency occupation. First, the original principle, inspired from quantum physics (levitons), is presented. Besides, we address the problem of low-complexity coherent detection of this new waveform, based on orthonormal wave-functions used to perform matched-filtering for efficient demodulation. Consequently, this shows that the proposed modulation can operate using existing digital communication technology , since only well-known operations are performed (e.g. filtering, integration). This SSB property can be exploited to allow large bit rates transmissions at low carrier frequency without caring about image frequency degradation effects typical of ordinary double side-band signals