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

Statistical evaluation of simulated NMR data of flexible molecules

A new probability score—named χ-probability—is introduced for evaluating the fit of mixed NMR datasets to calculate molecular model ensembles, in order to answer challenging structural questions such as the determination of stereochemical configurations.</jats:p

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

SHARP-TACSY: Triple-Band Tailored Correlated Spectroscopy for Base-to-Sugar Transfer in Nucleic Acid Residues with Intermediate Time Scale Motions

Established experiments to identify the sugar-to-base connectivity in isotopically labeled RNA require long transfer periods and are inefficient for residues undergoing intermediate time scale motions (microsecond to millisecond). Here, an alternative transfer experiment is introduced, whereby the C1‘−N1/9−C6/8 spin system is selectively brought to the so-called Hartmann−Hahn condition using selective heteronuclear planar triple-band tailored correlated spectroscopy (SHARP-TACSY). Results are shown for the fully labeled 30-mer oligonucleotide TAR RNA with particular attention placed on residues from and close to the bulge and the loop. For these residues, the faster relaxation can be attributed to exchange contributions stemming from transient stacking and unstacking of the bases and/or from the isomerization of the ribose sugar pucker. The new experiment shows improved signal-to-noise for residues exhibiting large microsecond−millisecond time scale motions with respect to established experiments, thus providing a valid alternative for resonance assignment in mobile RNA regions

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

An NMR Database for Organic and Organometallic Compounds

Databases of organic compounds are rooted in chemical formats, typically modeling chemical structures as simple graphical representations, which are easily readable by both humans and machines. This information can be handled by software and standards that have emerged in chemistry over decades and are well established. The present communication proposes that the extension of databases to encompass organometallic compounds, with coordination bonds, can be accomplished seamlessly with minor modifications, without compromising the utility of the database functionalities. Using a database for nuclear magnetic resonance (NMR) data, we demonstrate that this enables treating the organometallic compounds with the same algorithms as the organic compounds

Rhodium(<scp>i</scp>) complexes derived from tris(isopropyl)-azaphosphatrane—controlling the metal–ligand interplay

The synthesis and coordination chemistry of Rh(i) complexes bearing a tris(isopropyl)-azaphosphatrane (TiPrAP) ligand are reported. The adaptive nature of TiPrAP ligands allows for molecular control of the immediate environment of the metal center.</jats:p

¹³C-Detection in RNA Bases: Revealing Structure−Chemical Shift Relationships

The chemical shifts of the unprotonated carbons in the proton-deficient nucleobases of RNA are rarely reported, despite the valuable information that they contain about base-pairing and base-stacking. We have developed 13C-detected 2D-experiments to identify the unprotonated 13C in the RNA bases and have assigned all the base nuclei of uniformly 13C,15N-labeled HIV-2 TAR-RNA. The 13C chemical shift distributions revealed perturbations correlated with the base-pairing and base-stacking properties of all four base-types. From this work, we conclude that the information contained in the chemical shift perturbations within the base rings can provide valuable restraint information for solving RNA structures, especially in conformational averaged regions, where NOE-based information is not available