First Application of the Dakin-West Reaction to Fmoc Chemistry: Synthesis of the ketomethylene tripeptide Fmoc-Nα-Asp(tBu)-(R,S)Tyr(tBu)Ψ(CO-CH2)Gly-OH

International audienceA practical synthesis of a tripeptide containing a ketomethylene isostere, suitably protected for introduction in Fmoc SPPS, has been carried out for the first time in Fmoc chemistry by using a modified Dakin-West reaction

On combining wavelets expansion and sparse linear models for Regression on metabolomic data and biomarker selection

International audienceWavelet thresholding of spectra has to be handled with care when the spectra are the predictors of a regression problem. Indeed, a blind thresholding of the signal followed by a regression method often leads to deteriorated predictions. The scope of this article is to show that sparse regression methods, applied in the wavelet domain, perform an automatic thresholding: the most relevant wavelet coefficients are selected to optimize the prediction of a given target of interest. This approach can be seen as a joint thresholding designed for a predictive purpose. The method is illustrated on a real world problem where metabolomic data are linked to poison ingestion. This example proves the usefulness of wavelet expansion and the good behavior of sparse and regularized methods. A comparison study is performed between the two-steps approach (wavelet thresholding and regression) and the one-step approach (selection of wavelet coefficients with a sparse regression). The comparison includes two types of wavelet bases, various thresholding methods, and various regression methods and is evaluated by calculating prediction performances. Information about the location of the most important features on the spectra was also obtained and used to identify the most relevant metabolites involved in the mice poisoning

Raman Investigations to Identify Corallium rubrum in Iron Age Jewelry and Ornaments

International audienceDuring the Central European Iron Age, more specifically between 600 and 100 BC, red precious corals (Corallium rubrum) became very popular in many regions, often associated with the so-called (early) Celts. Red corals are ideally suited to investigate several key questions of Iron Age research, like trade patterns or social and economic structures. While it is fairly easy to distinguish modern C. rubrum from bone, ivory or shells, archaeologists are confronted with ancient, hence altered, artifacts. Due to ageing processes, archaeological corals lose their intensive red color and shiny surface and can easily be confused with these other light colored materials. We propose a non-destructive multi-stage approach to identify archaeological corals amongst other biominerals used as ornament during the central European Iron Age with emphasis on optical examination and mobile Raman spectroscopy. Our investigations suggest that the noticeably high amount of misidentifications or at least uncertain material declarations existing in museums or even in the literature (around 15%) could be overcome by the proposed approach. Furthermore, the range of different materials is higher than previously expected in archaeological research. This finding has implications for contemporary concepts of social structures and distribution networks during the Iron Age

Application des micro-spectrométries infrarouge et Raman à l’étude des processus diagénétiques altérant les ossements paléolithiques

Différents processus post-mortem peuvent altérer les ossements et limiter l’utilisation de leur composition élémentaire et isotopique comme marqueurs paléo-environnementaux/climatiques, paléo-alimentaires ou encore géochronologiques. De part leur structure complexe et hiérarchisée, les ossements in vivo sont des tissus hétérogènes. La prise en compte de cette hétérogénéité, renforcée au cours de la fossilisation, nécessite l’utilisation de techniques d’analyses adaptées permettant l’étude des variations de structure et de compositions à micro-échelle. De précédents travaux ont montré que des techniques de micro-spectrométrie vibrationnelle telle que la micro-spectrométrie infrarouge pouvait permettre de caractériser les modifications induites par les processus diagénétiques et de déterminer les états de préservation des échantillons fossiles. Dans cette étude, des indices permettant de déterminer la composition d’ossements fossiles ont été acquis en spectrométrie infrarouge et Raman, ceci dans le but de comparer les informations fournies par ces deux techniques. Les micro-spectrométries IR et Raman ont ensuite été appliquées à des échantillons fossiles préparés sous forme de coupes minces ou de lames épaisses. Ces premiers résultats de cartographie obtenus par micro-spectrométrie Raman permettent de mettre en évidence l’apport de cette technique à la compréhension des processus diagénétiques en permettant de déterminer la répartition des principaux composés des ossements fossiles (teneur en collagène, en carbonates, cristallinité de la phase minérale, etc.).Various post-mortem processes can alter bone materials and then limit the use of their elemental or isotopic composition as markers for palaeo-environmental/climatic, paleodiet, or geochronological studies. Due to their complex and hierarchical structure, in vivo bones correspond to a highly heterogeneous tissue. The study of this heterogeneity, reinforced during fossilization processes, requires the use of adapted analytical techniques to investigate the variation of composition at microscale. Previous works have demonstrated that vibrational spectroscopic techniques like infrared micro-spectroscopy can be used to characterize the modification of composition induced by diagenetic processes and to determine the preservation state of the fossil samples. In this study, some spectral parameters, used to determine the composition of fossil bones, were measured by both infrared and Raman spectroscopy in order to compare the information supplied by these two techniques. Infrared and Raman micro-spectroscopy were then applied to fossil samples prepared as thin sections or polished thick sections. These first results of chemical mapping obtained on fossil bones by Raman micro-spectroscopy are in good agreement with the data obtained by FTIR micro-spectroscopy. These results demonstrated the capacity of this method for the understanding of diagenetic processes by monitoring the main components of fossil bone tissues (carbonates and collagen content, mineral crystallinity, etc.)

Les cuirs dorés polychromes et le multi-accès FIXLAB CHARISMA : genèse d’une recherche innovante

L’accès à de grands instruments au travers du programme européen CHARISMA a permis d’initier un programme de recherche sur les cuirs dorés polychromes s’appuyant sur une méthodologie analytique innovante avec une équipe pluridisciplinaire. Ce type de décors, principalement fabriqués entre le xvie et le xviiie siècle en Europe, est rarement signé. Leur datation et leur provenance sont donc actuellement déduites le plus souvent de leur facture et de leurs caractères stylistiques. L’utilisation combinée des analyses PIXE et RBS sur l’accélérateur AGLAE et de la ligne infrarouge du synchrotron SOLEIL a permis d’analyser les différents composés présents dans ces œuvres : cuir, vernis, feuille d’argent. Les recherches se sont ensuite focalisées sur la caractérisation de l’argent à partir d’un corpus d’échantillons pour tenter de trouver des marqueurs permettant une meilleure classification de ces œuvres et une meilleure compréhension des dégradations observées. L’article expose les principales étapes de cette recherche qui a pour objectif une plus grande connaissance des techniques de fabrication ouvrant vers des identifications plus précises des œuvres et de meilleures approches de conservation.Access to large-scale facilities through the European project CHARISMA enabled a research program to be launched on gilt leather, involving innovative analytical methodology and a multidisciplinary team. Such decorative leather, produced in Europe mainly between the 16th and 18th centuries, were seldom signed. Nowadays, date and origin are generally deduced from their manufacturing and stylistic characteristics. The combined use of PIXE and RBS analysis on the AGLAE accelerator and the infrared beamline at the SOLEIL synchrotron has enabled researchers to analyse the different components present in these artefacts: leather, varnish, silver leaf. Based on a corpus of gilt leather samples, research then focused on the characteristics of the silver leaf, in an attempt to identify markers that would help classify these decors and shed more light into the deterioration observed. This paper describes the main steps of this research which seeks to broaden understanding of the manufacturing techniques employed and thus help better assign these decors and improve conservation approaches

New 8-nitroquinolinone derivative displaying submicromolar in vitro activities against both Trypanosoma brucei and cruzi

International audienceAn antikinetoplastid pharmacomodulation study was conducted at position 6 of the 8-nitroquinolin-2(1H)-one pharmacophore. Fifteen new derivatives were synthesized and evaluated in vitro against L. infantum, T. brucei brucei, and T. cruzi, in parallel with a cytotoxicity assay on the human HepG2 cell line. A potent and selective 6-bromo-substituted antitrypanosomal derivative 12 was revealed, presenting EC50 values of 12 and 500 nM on T. b. brucei trypomastigotes and T. cruzi amastigotes respectively, in comparison with four reference drugs (30 nM ≤ EC50 ≤ 13 μM). Moreover, compound 12 was not genotoxic in the comet assay and showed high in vitro microsomal stability (half life >40 min) as well as favorable pharmacokinetic behavior in the mouse after oral administration. Finally, molecule 12 (E° = −0.37 V/NHE) was shown to be bioactivated by type 1 nitroreductases, in both Leishmania and Trypanosoma, and appears to be a good candidate to search for novel antitrypanosomal lead compounds

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Altimetry for the future: building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Méthodologies spectroscopiques pour l'étude de matériaux : objets du patrimoine de la fin du 19ème au début du 20ème siècle

At the end of the 19th century, everyday objects like buttons, fans, dolls ... progressively incorporated celluloïd, acetocellulose or galalith parts imitating the long time used nacre, wood, horn, tortoiseshell, ivory and bone. Not only was the cost lowered by the use of artificial materials but they also offered a larger palette of colors than the natural ones. As a matter of fact, the imitation effect was so good it makes it very difficult to tell what an object from that period, which since became an heritage object, is actually made of. The aim of our study was to establish an analysis methodology to unambiguously identify the above-mentioned artificial and natural materials. Most heritage materials being unique, the analysis had to be totally non-destructive, which led us to concentrate on Raman and infrared-ATR spectroscopies. Besides, the chemical compositions being different, we soon realized a single method would not apply to all cases. Our main conclusions are the following : - nacre and wood can be identified by simple comparison between their Raman spectra and reference spectra. The same is true of celluloïd and acetocellulose, for which we had to establish reference spectra, based on their principal components. - proteinaceous materials (horn, tortoiseshell and galalith) can be identified by the spectral analysis of the amide I bands of their infrared-ATR spectra. - ivory and bone can be discriminated by a chemometric analysis (principal components analysis) run over their fullrange infrared-ATR spectra. All these identification strategies have been applied to fans and buttons from the collections of the musée Galliera (Paris) that were dated between the late 19th and the early 20th centuries. The material of each of them has been identified.A partir de la fin du 19ème siècle, des matériaux artificiels (le celluloïd, l'acétocellulose et la galalithe) sont mis au point et employés pour la fabrication d'objets de la vie quotidienne, en même temps que des matériaux naturels (nacre, bois, corne, écaille, ivoire et os), utilisés depuis toujours. Ces matériaux artificiels sont utilisés, dans un premier temps, pour imiter les matières naturelles, puis, dans un second temps, pour proposer d'autres formes et un choix de couleurs plus large. Aujourd'hui, l'enjeu est de mettre au point des méthodologies d'analyses afin de différencier et d'identifier ces matériaux qu'ils soient naturels ou artificiels. Les objets que nous avons analysés sont des éventails et des boutons, datés entre la fin du 19ème et le début du 20ème siècle, et conservés dans les collections du musée Galliera, à Paris. Les méthodologies d'analyse doivent être totalement non-destructives. Deux techniques d'analyses répondent à ce critère : la spectroscopie Raman et la spectroscopie infrarouge-ATR (Attenuated Total Reflexion). Les compositions chimiques de ces neuf matériaux étant extrêmement diversifiées, une unique méthodologie ne peut suffire à les identifier tous. Aussi, nous avons établi plusieurs stratégies d'identification, adaptées à chaque type de matériau. Les matériaux naturels, nacre et bois, sont identifiés par comparaison de leurs spectres Raman à des spectres de référence. Les matériaux artificiels, celluloïd et acétocellulose, sont aussi identifiés en spectroscopie Raman, par référence à leurs composants principaux. L'analyse spectrale des bandes amide I des spectres infrarouge-ATR de la corne, de l'écaille et de la galalithe a permis la détermination des structures secondaires de ces matériaux, conduisant à leur différenciation. Enfin, la différenciation des ivoires et des os nécessite l'application d'une analyse chimiométrique (analyse en composantes principales) de l'ensemble de leurs spectres infrarouge-ATR. Toutes ces stratégies d'identification ont été appliquées aux éventails et boutons du musée Galliera, et le matériau de chacun d'entre eux a été soit caractérisé, soit identifié. Ces identifications ont permis, entre autre, la mise en évidence de l'introduction précoce des matériaux artificiels dans la fabrication d'accessoires de mode (éventail de 1885 identifié en celluloïd)

Méthodologies spectroscopiques pour l'étude de matériaux (objets du patrimoine de la fin du 19ème au début du 20ème siècle)

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF