Influence of Phosphoramidites in Copper-Catalyzed Conjugate Borylation Reaction

Copper(I) has become the preferred metal to catalyze the β-boration of α,β-unsaturated carbonyl compounds, and now we demonstrate that easily accessible monodentate chiral ligands, such as phosphoramidites and phosphites, can be convenient alternative ligands to induce asymmetry in the enantioselective version of this reaction, particularly in the β-boration of α,β-unsaturated imines.

Extracting non-linear integrate-and-fire models from experimental data using dynamic I - V curves

The dynamic I-V curve method was recently introduced for the efficient experimental generation of reduced neuron models. The method extracts the response properties of a neuron while it is subject to a naturalistic stimulus that mimics in vivo-like fluctuating synaptic drive. The resulting history-dependent, transmembrane current is then projected onto a one-dimensional current-voltage relation that provides the basis for a tractable non-linear integrate-and-fire model. An attractive feature of the method is that it can be used in spike-triggered mode to quantify the distinct patterns of post-spike refractoriness seen in different classes of cortical neuron. The method is first illustrated using a conductance-based model and is then applied experimentally to generate reduced models of cortical layer-5 pyramidal cells and interneurons, in injected-current and injected- conductance protocols. The resulting low-dimensional neuron models—of the refractory exponential integrate-and-fire type—provide highly accurate predictions for spike-times. The method therefore provides a useful tool for the construction of tractable models and rapid experimental classification of cortical neuron

La mer d’Iroise : une singularité dans l’approvisionnement en silex des hommes du Paléolithique breton

L’étude des prélèvements réalisés en mer d’Iroise montre que cette région, contrairement au reste de la marge continentale bretonne, semble dépourvue de cordons littoraux anciens sous le niveau des plus hautes mers actuelles. Cette particularité résulte de la densité des anciennes rivières, reconnues grâce à leurs paléo-vallées, qui ont provoqué un fort effet de chasse et au décapage des sédiments déposés lors de chaque régression importante de la mer. Par ailleurs, lors des périodes transgressives, la distance importante qui existe entre les sources de silex et les cordons de galets côtiers actuels a provoqué un important tri granulométrique. De telle façon que ce cordon ne livre que des galets de petite taille, à l’exception toutefois de rares rognons plus massifs d’origine glacielle, qui sont arrivés plus tard et dont l’origine est inconnue. Cette configuration particulière se reflète dans la lithologie et la dimension de l’outillage lithique des premiers habitants qui vivaient en bordure de l’Iroise (Paléolithique inférieur). Ceux-ci étaient moins favorisés que ceux qui occupaient les rivages de la Baie d’Audierne (Menez-Dregan). Toutefois, à défaut de silex, ils pouvaient disposer, en relative abondance et à peu de distance, d’autres matériaux tels que les quartzites de la presqu’île de Crozon ou les grès éocènes de la vallée du Juch (Kervouster). Mais, ici encore, il semble qu’ils aient préféré le silex et privilégié un approvisionnement local.Study of the sediments sampled in the Iroise Sea shows that this particular area, contrary to the other shelves surrounding Brittany, does not display any boulder bar. This particularity results from the strong flushing developed by the local braided rivers which were running on the shelf during each regression of the sea. On the other hand, the long distance which exists between the source of the flints and the present remains of the coastal boulder bar, was large enough to be responsible for a strong granulometric selection of the boulders during each transgressive episodes. It is the reason why the actual coastal boulder bar is almost only made of small sized boulders. Some associated rare and bigger elements were deposited by ice rafts during a more recent period of time. This particular environment is well expressed in the lithology and size of the lithic tools. The first inhabitants living along the Iroise sea shore (Lower Palaeolithic) were rather less favoured than those living close to the Audierne Bay (Menez Dregan) and were often forced to use different types of rocks, such as the Paleozoïc or Eocene sandstones of the valley of Le Juch (Kervouster), to replace the missing flints. But even in this case, it seems that they preferred flints to another kind of rocks and favoured a local supply

A detailed study of the diastereoselective catalytic hydrogenation of 6-hydroxytetrahydroisoquinoline-(3R)-carboxylic ester intermediates

A key step towards a highly-selective antagonist of ionotropic glutamate receptors entails the diastereoselective arene hydrogenation of an enantiopure tetrahydroisoquinoline. An extensive screen using parallel reactors was conducted and led to the discovery of several Pd/C catalysts giving high yield and improved diastereoselectivity from 75 : 25 to 95 : 5. A detailed kinetic study of the best system was performed and supports the reduction occuring in two-steps.

Apport de la géologie marine à la détermination des sources de matières premières au paléolithique dans le massif armoricain : origine possible du silex utilisé sur les stations paléolithique inférieur de Menez‑Dregan (Plouhinec, Finistère, France). Implications paléoclimatiques et paléoenvironnementales

Le silex n’est pas présent dans le sous‑sol armoricain. Sa mise en œuvre au Paléolithique est principalement liée à la collecte de galets marins prélevés dans les cordons littoraux à différents niveaux. Toutefois, dans la couche 5d’ de Menez‑Dregan1, apparaissent des éclats de silex dont le cortex ne porte pas trace d’un transport important. L’exploitation des minutes de dragages et carottages au large de la Baie d’Audierne montre que, pour une part, le matériau qui a servi à la taille de l’outillage récolté au niveau 5d’ de Menez Dregan peut provenir d’un estran situé vers ‑40 m et localisé à une distance de 5 à 10 km de la côte actuelle lors d’une phase de régression marine associée à un début de dégradation climatique. Ces résultats sont en remarquable concordance avec ceux de la paléobotanique (anthracologie). Ceci nous donne des indications paléogéographiques et paléoenvironnementales importantes pour la connaissance des occupations paléolithiques à l’Ouest de la Bretagne.There is no flint in the armorican terrain. Its use during Palaeolithic is mainly dependent from the gathering of marine pebbles taken along the old shorelines located at different levels. However, at Menez‑Dregan1 layer 5d’, flint flakes do not show the cortex aspect which witness for a long transport. Analysis of dredging and coring samples made off Baie d’Audierne shows that, part of the raw material used to make the tools from Menez‑Dregan1 layer 5d’ may come from an old shore located at about ‑40 m depth and at a distance of 5 to 10 km from the actual coast, which developed during a marine regression phase associated with the beginning of a climatic deterioration. These results are in strong concordance with those of paleobotany (anthracology). They provide paleo‑geographic and paleoenvironmental informations for a better knowledge of the Palaeolithic presence in Western Brittany

Rapid Identification of a Scalable Catalyst for the Asymmetric Hydrogenation of a Sterically Demanding Aryl Enamide

High throughput screening was used to find a cost-effective and scalable catalyst for the asymmetric hydrogenation of a sterically demanding enamide as an intermediate towards a new potent melanocortin receptor agonist useful in the treatment of obesity. Lessons drawn from the testing of a first library of 96 chiral monodentate phosphoramidites led to the design of a second focused library of 16 chiral ligands, allowing the discovery of a new efficient catalyst. This catalyst was based on rhodium and a bulky monodentate phosphite ligand. The catalyst was scaled up and used in the kilogram production of the desired bulky chiral amide

Improved estimation of the left ventricular ejection fraction using a combination of independent automated segmentation results in cardiovascular magnetic resonance imaging

—This work aimed at combining different segmenta-tion approaches to produce a robust and accurate segmentation result. Three to five segmentation results of the left ventricle were combined using the STAPLE algorithm and the reliability of the resulting segmentation was evaluated in comparison with the result of each individual segmentation method. This comparison was performed using a supervised approach based on a reference method. Then, we used an unsupervised statistical evaluation, the extended Regression Without Truth (eRWT) that ranks different methods according to their accuracy in estimating a specific biomarker in a population. The segmentation accuracy was evaluated by focusing on the left ventricular ejection fraction (LVEF) estimate resulting from the LV contour delineation using a public cardiac cine MRI database. Eight different segmentation methods, including three expert delineations, were studied, and sixteen combinations of the five automated methods were investigated. The supervised and unsupervised evaluations demonstrated that in most cases, STAPLE results provided better estimates of the LVEF than individual automated segmentation methods. In addition, LVEF obtained with STAPLE were within inter-expert variability. Overall, combining different automated segmentation methods improved the reliability of the segmenta-tion result compared to that obtained using an individual metho