Etude théorique de la structure et de la réactivité de complexes de lanthanides et d'actinides : activation de petites molécules

Cette thèse présente une étude théorique au niveau DFT de la structure et de la réactivité de complexes organométalliques de lanthanides et d'actinides. Après une introduction générale aux méthodes de chimie théorique employées pour traiter la réactivité de complexes organométalliques, une étude de la participation des électrons 5f dans la réactivité des complexes d'uranium(IV) est présentée. Il est montré qu'il est possible d'utiliser sans crainte des pseudopotentiels relativistes à grand cœur pour un certain nombre de problèmes de réactivité et qu'ainsi les électrons 5f peuvent être traités de manière implicite. Ensuite, la réactivité de complexes d'uranium(III) avec CO2 et autres molécules analogues est étudiée à travers plusieurs exemples issus de la littérature. Ces études montrent que la nature stérique des ligands impliqués est d'une importance capitale et contrôle la réactivité. Cette étude est étendue à un complexe de samarium(II). Enfin, la réactivité entre un complexe hydrure de cérium(III) et MeOSO2Me est étudiée et les résultats théoriques sont comparés aux observations expérimentales.This PhD thesis presents a theoretical study of the structure and the reactivity of organometallic complexes of lanthanides and actinides at the DFT level. After a general introduction of the methods of theoretical chemistry used for the modelling of organometallic reactivity, a study of the participation of 5f electrons in uranium(IV) reactivity is presented. The results show that the large core ECP can be used safely in order to treat the actinide and so that 5f electrons can be treated implicitly. Then, the reactivity of uranium(III) complexes with CO2 and other analogous molecules is studied via multiple examples from the literature. These studies show that the steric nature of the ligands is very important and controls the reactivity. This study is then extended to samarium(II) complex. Eventually, the reactivity of a hydride complex of cerium(III) with MeOSO2Me is investigated and theoretical results are compared with experimental observations

Insights into structure and redox potential of lignin peroxidase from QM/MM calculations

The authors wish to thank EaStCHEM, the School of Chemistry and the EPSRC (grant code EP/J018139/1) for fundingRedox potentials are computed for the active form (compound I) of lignin peroxidase (LiP) using a suitable QM/MM methodology (B3LYP/SDD/6-311G**//BP86/SVP:CHARMM). Allowing for dynamic conformational averaging, a potential of 0.67(33) V relative to ferrocenium/ferrocene is obtained for the active form with its oxoiron(IV) core. The computed redox potential is very sensitive to the charge distribution around the active site: protonation of titratable residues close to the metal center increases the redox potential, thereby rationalising the known pH dependence of LiP activity. A simple MM-charge deletion scheme is used to identify residues that are critical for the redox potential. Two mutant proteins are studied through homology modelling, E40Q and D183N, which are predicted to have an increased redox potential by 140 mV and 190 mV, respectively, relative to the wild type. These mutant proteins are thus promising targets for synthesis and further exploration toward a rational design of biocatalytic systems for oxidative degradation of lignin.Publisher PDFPeer reviewe

Water in the Green Economy: Capacity Development Aspects

This book discusses needs related to capacity development for water resources management, including water supply and sanitation, in the context of the green economy. It showcases theoretical and practical approaches with proven success. Most contributions come from members and partners within the interagency mechanism, UN-Water. The 11 case studies in this book range from innovative design and delivery of capacity development programs related to water in the green economy, market mechanisms, and quality control procedures supporting capacity development success towards the practical implementation of programs to enhance individual and institutional capacity

Stratus Ocean Reference Station (20˚S, 85˚W), mooring recovery and deployment cruise R/V Ronald H. Brown cruise 05-05, September 26, 2005–October 21, 2005

The Ocean Reference Station at 20°S, 85°W under the stratus clouds west of northern Chile is being maintained to provide ongoing, climate-quality records of surface meteorology, of air-sea fluxes of heat, freshwater, and momentum, and of upper ocean temperature, salinity, and velocity variability. The Stratus Ocean Reference Station (ORS Stratus) is supported by the National Oceanic and Atmospheric Administration’s (NOAA) Climate Observation Program. It is recovered and redeployed annually, with cruises that have come between October and December. During the October 2005 cruise of NOAA’s R/V Ronald H. Brown to the ORS Stratus site, the primary activities were recovery of the WHOI surface mooring that had been deployed in December 2004, deployment of a new WHOI surface mooring at that site, in-situ calibration of the buoy meteorological sensors by comparison with instrumentation put on board by staff of the NOAA Environmental Technology Laboratory (ETL), and observations of the stratus clouds and lower atmosphere by NOAA ETL. The ORS Stratus buoys are equipped with two Improved Meteorological (IMET) systems, which provide surface wind speed and direction, air temperature, relative humidity, barometric pressure, incoming shortwave radiation, incoming longwave radiation, precipitation rate, and sea surface temperature. The IMET data are made available in near real time using satellite telemetry. The mooring line carries instruments to measure ocean salinity, temperature, and currents. The ETL instrumentation used during the 2005 cruise included cloud radar, radiosonde ballons, and sensors for mean and turbulent surface meteorology. In addition, two technicians from the University of Concepcion collected water samples for chemical analysis. Finally, the cruise hosted a teacher participating in NOAA’s Teacher at Sea Program.Funding was provided by the National Oceanic and Atmospheric Administration under Grant No. NA17RJ1223 and the Cooperative Institute for Climate and Ocean Research (CICOR)

Tratamiento de espectros FTIR con el programa PALME: una nueva herramienta para diagnosticar el estado de conservación de hierros arqueológicos

International audienceEl proceso que va del descubrimiento de una pieza arqueológica a su musealización pasa necesariamente por una fase de restauración. En el caso de piezas de naturaleza metálica la restauración puede comportar la eliminación mecánica de las costras de degradación más externas. Los fragmentos eliminados contienen una gran cantidad de información que, si es extrapolada, puede ayudar a los restauradores a elegir los tratamientos más adecuados de conservación. Por esta razón, con el presente trabajo se pretende desarrollar un nuevo método que permita semicuantificar de manera rápida y fiable las fases de corrosión contenidas en los residuos de limpieza de hierros arqueológicos. Para realizar el trabajo ha sido utilizado el software PALME para el tratamiento de los resultados obtenidos mediante espectroscopia infrarroja (FTIR) sobre mezclas de corrosiones puras a concentración conocida. Gracias a los resultados obtenidos se puede afirmar que el método desarrollado, una vez optimizado, representará una herramienta útil para la rápida semicuantificación de las corrosiones que normalmente afectan los hierros arqueológicos

From Weak Lensing to non-Gaussianity via Minkowski Functionals

We present a new harmonic-domain approach for extracting morphological information, in the form of Minkowski Functionals (MFs), from weak lensing (WL) convergence maps. Using a perturbative expansion of the MFs, which is expected to be valid for the range of angular scales probed by most current weak-lensing surveys, we show that the study of three generalized skewness parameters is equivalent to the study of the three MFs defined in two dimensions. We then extend these skewness parameters to three associated skew-spectra which carry more information about the convergence bispectrum than their one-point counterparts. We discuss various issues such as noise and incomplete sky coverage in the context of estimation of these skew-spectra from realistic data. Our technique provides an alternative to the pixel-space approaches typically used in the estimation of MFs, and it can be particularly useful in the presence of masks with non-trivial topology. Analytical modeling of weak lensing statistics relies on an accurate modeling of the statistics of underlying density distribution. We apply three different formalisms to model the underlying dark-matter bispectrum: the hierarchical ansatz, halo model and a fitting function based on numerical simulations; MFs resulting from each of these formalisms are computed and compared. We investigate the extent to witch late-time gravity-induced non-Gaussianity (to which weak lensing is primarily sensitive) can be separated from primordial non-Gaussianity and how this separation depends on source redshift and angular scale.Comment: 22 Pages, 12 Figures. Submitting To MNRA

Specialized Astrocytes Mediate Glutamatergic Gliotransmission in the CNS

Multimodal astrocyte–neuron communications govern brain circuitry assembly and function. For example, through rapid glutamate release, astrocytes can control excitability, plasticity and synchronous activity of synaptic networks, while also contributing to their dysregulation in neuropsychiatric conditions. For astrocytes to communicate through fast focal glutamate release, they should possess an apparatus for Ca2+-dependent exocytosis similar to neurons. However, the existence of this mechanism has been questioned owing to inconsistent data and a lack of direct supporting evidence. Here we revisited the astrocyte glutamate exocytosis hypothesis by considering the emerging molecular heterogeneity of astrocytes and using molecular, bioinformatic and imaging approaches, together with cell-specific genetic tools that interfere with glutamate exocytosis in vivo. By analysing existing single-cell RNA-sequencing databases and our patch-seq data, we identified nine molecularly distinct clusters of hippocampal astrocytes, among which we found a notable subpopulation that selectively expressed synaptic-like glutamate-release machinery and localized to discrete hippocampal sites. Using GluSnFR-based glutamate imaging in situ and in vivo, we identified a corresponding astrocyte subgroup that responds reliably to astrocyte-selective stimulations with subsecond glutamate release events at spatially precise hotspots, which were suppressed by astrocyte-targeted deletion of vesicular glutamate transporter 1 (VGLUT1). Furthermore, deletion of this transporter or its isoform VGLUT2 revealed specific contributions of glutamatergic astrocytes in cortico-hippocampal and nigrostriatal circuits during normal behaviour and pathological processes. By uncovering this atypical subpopulation of specialized astrocytes in the adult brain, we provide insights into the complex roles of astrocytes in central nervous system (CNS) physiology and diseases, and identify a potential therapeutic target

Oxo-Functionalization and Reduction of the Uranyl Ion through Lanthanide-Element Bond Homolysis:Synthetic, Structural, and Bonding Analysis of a Series of Singly Reduced Uranyl-Rare Earth 5f¹-4f^<em>n</em> Complexes

The heterobimetallic complexes [{UO2Ln-(py)2(L)}2], combining a singly reduced uranyl cation and a rare-earth trication in a binucleating polypyrrole Schiff-base macrocycle (Pacman) and bridged through a uranyl oxo-group, have been prepared for Ln = Sc, Y, Ce, Sm, Eu, Gd, Dy, Er, Yb, and Lu. These compounds are formed by the single-electron reduction of the Pacman uranyl complex [UO2(py)(H2L)] by the rare-earth complexes LnIII(A)3 (A = N(SiMe3)2, OC6H3But 2-2,6) via homolysis of a Ln−A bond. The complexes are dimeric through mutual uranyl exo-oxo coordination but can be cleaved to form the trimetallic, monouranyl “ate” complexes [(py)3LiOUO(μ-X)Ln(py)(L)] by the addition of lithium halides. X-ray crystallographic structural characterization of many examples reveals very similar features for monomeric and dimeric series, the dimers containing an asymmetric U2O2 diamond core with shorter uranyl U=O distances than in the monomeric complexes. The synthesis by LnIII−A homolysis allows [5f1-4fn]2 and Li[5f1-4fn] complexes with oxobridged metal cations to be made for all possible 4fn configurations. Variable-temperature SQUID magnetometry and IR, NIR, and EPR spectroscopies on the complexes are utilized to provide a basis for the better understanding of the electronic structure of f-block complexes and their f-electron exchange interactions. Furthermore, the structures, calculated by restricted-core or allelectron methods, are compared along with the proposed mechanism of formation of the complexes. A strong antiferromagnetic coupling between the metal centers, mediated by the oxo groups, exists in the UVSmIII monomer, whereas the dimeric UVDyIII complex was found to show magnetic bistability at 3 K, a property required for the development of single-molecule magnets.JRC.E.6-Actinide researc

Genomic value of isocitrate-dehydrogenase (IDH1/2) in glioma origin and progression (ONCOLGroup)

Las mutaciones heterocigotas del gen que codifica la isocitrato deshidrogenasa (IDH) ocurren con relativa frecuencia en los gliomas; sin embargo, su relevancia durante el desarrollo tumoral es desconocida. Estas alteraciones provocan una pérdida en la afinidad de la enzima por el sustrato, inhibiendo la actividad de la isoforma silvestre de la IDH1 a través de la formación de heterodímeros inactivos. La expresión forzada de la mutación IDH1/2 en cultivos celulares reduce la formación del producto de la enzima, el α-ketoglutarato (α-KG), e incrementa los niveles del factor inducido por la hipoxia tipo 1 (HIF-1α, un elemento de transcripción que facilita el crecimiento tumoral en presencia de bajas concentraciones de oxígeno, hallazgo regulado en parte por el α-KG. La expresión del HIF-1α suele ser mayor entre los gliomas portadores de la mutación IDH, en los que la vía de señalización del HIF está implicada en su progresión. Varios grupos independientes han demostrado el papel que tienen las mutaciones del gen IDH1/2 como marcador pronóstico, especialmente para los pacientes con gliomas de bajo grado y con glioblastomas secundarios que presentan un patrón oligodendroglial. Este conocimiento proporciona una clara oportunidad para mejorar las estrategias diagnósticas y terapéuticas para los pacientes con gliomas, que en la actualidad no se encuentran dirigidas contra alteraciones moleculares específicas. Este artículo presenta una revisión detallada del papel de las mutaciones del gen IDH en la progresión y el mantenimiento de los gliomas, y explora algunas opciones terapéuticas dirigidas contra este entorno.Revisión de tema22-33Heterozygous mutations in the gene encoding isocitrate dehydrogenase (IDH) occur in gliomas, but their mechanistic role in tumor development is unknown. Tumor-derived IDH mutations impair the enzyme affinity for its substrate and dominantly inhibit wild-type IDH1 activity through the formation of catalytically inactive heterodimers. Forced expression of mutant IDH1 in cultured cells reduces formation of the enzyme product, α-ketoglutarate (α-KG), and increases the levels of hypoxia-inducible factor subunit 1 (HIF-1α, a transcription factor that facilitates tumor growth when oxygen is low and whose stability is regulated by α-KG. HIF-1α levels were higher in human gliomas harboring an IDH1 mutation than in tumors without a mutation, thus, IDH1/2 contributes to tumor progression in part through induction of the HIF-1 pathway. Numerous independent research groups had demonstrated the role of IDH mutations as a prognostic marker, especially for those patients with low grade gliomas and secondary glioblastomas with oligodendroglial pattern. This knowledge indicates great opportunities to improve diagnostic and therapeutic strategies for gliomas, which are not currently targeted at the specific molecular alterations. This paper presents a detailed review of the role of the IDH gene mutations in progression and manteinance of gliomas, and explores some therapeutic options directed against this environment

Metastatic non-small cell lung cancer. Current treatment based on evidence (ONCOLGroup)

Propósito: realizar una revisión de la evidencia acerca del tratamiento del cáncer de pulmón de célula no pequeña (CPCNP). Fuente de los datos: la información se obtuvo a partir de búsquedas practicadas en MEDLINE, CCTR, BIOSIS, EMBASE, LILACS y CINHAL. También se recopilaron las referencias más representativas presentadas durante los últimos cinco años en los congresos ASCO, ESMO y de la IASLC. Extracción de los datos: los datos fueron extraídos por miembros asociados al ONCOLGroup. La recopilación de la información no siguió una estrategia uniforme. Resultados de la síntesis de datos: la terapia que se utiliza para tratar el carcinoma de pulmón de células no pequeñas (CPCNP) mejora la supervivencia global y la calidad de vida; no obstante, la mayoría de los pacientes mueren por la enfermedad antes del segundo año del diagnóstico, evento que ha favorecido la generación de nuevas estrategias que permitirán optimizar este desenlace. En la actualidad, el tratamiento estándar de primera línea implica varias combinaciones con base en algún platino que incrementan la supervivencia en comparación con la monoterapia y el mejor soporte paliativo. Estos regímenes son comparables respecto de su eficacia, pero difieren en el perfil de seguridad. Nuevas alternativas de tratamiento dirigidas contra blancos moleculares benefician a poblaciones específicas, cuando se administran solas o con otros agentes con los que presentan sinergismo. Esta revisión no realizó una evaluación sistemática de la evidencia. Conclusión: la terapia médica utilizada en el CPCNP modifica positivamente los desenlaces principales, incluyendo la calidad de vida.Artículo original53-81Purpose: to perform a review of evidence about the treatment of non-small cell lung cancer (NSCLC). Source of data: the information was obtained from searches conducted in MEDLINE, CCTR, BIOSIS, EMBASE, LILACS and CINHAL. We also collected the most representative references presented during the last five years at ASCO, ESMO and IASLC. Data extraction: data were extracted by associate members to the ONCOLGroup. The collection of information did not follow a uniform strategy. Results of data synthesis: therapy for NSCLC can prolong survival and improve quality of life, but the majority of advanced stage patients dies due to disease progression within 2 years, meaning thatthere is room for improvement. The standard chemotherapy for NSCLC involves one of a number of platinum-based doublets that have been shown to improve survival when compared with single agents or best supportive care. These doublets are generally comparable in terms of efficacy, differing primarily in their toxicity profiles. However, encouraging new options may be approaching, including therapies targeted to specific patient subpopulations, and the use of combinations of current and new drugs to produce synergistic effects. This review present a detailed analysis of current evidence regarding the treatment of NSCLC based on a representative case series. This review didn’t conduct a systematic evaluation of the evidence