We propose to develop a set of models for the dynamics of the base of Earth mantle, interacting with the core, in the framework of the basal magma ocean (BMO). The ultimate goal is to test the validity of this concept to explain the current observations of the deep Earth and obtain a quantitative understanding of the various phenomena at stake. Five main tasks have been identified. 1-Several scenarios for the formation of the BMO will be developed. 2-The chemical interactions of the BMO with the core will be studied and their consequences for the stability of the core and the BMO considered. 3-A model of convection in the mantle interacting with a layer of dense crystals growing at its base will be developed to study the stabilization of thermo-chemical piles resulting from the crystallization of the BMO. 4-A model of convection in the BMO will allow the study of the thermal coupling between the core and the mantle. 5-Finally, we will develop a two-phase fluid model to study the partial melting zone at the interface between the BMO and the solid mantle and for the formation of the basal magma ocean. At the end of the 4-year period of this project, we hope to have a self-consistent global vision of the deep Earth at different times.

Tremendous amount of work on molecular-based magnets has been reported in the literature. - Such magnetic compounds and particularly zero-dimensional clusters (so-called Single Molecule - Magnets, SMMs) are currently subjects to spectacular interest since original magnetic materials - with high-density information storage potential can be anticipated. Different strategies along with - flourishing experimental techniques have been developed to investigate the unusual physical - properties of these magnetic molecules and nanowires (Single Chain Magnets, SCMs). Even - though these systems are not strictly 3D ordered compounds, the presence of hysterisis loop - below a blocking temperature is a reminiscence of classical magnets. - With this goal in mind, different synthetic routes - have been considered and are currently subject to intense work. - A detailed understanding of the magnetic phenomena in sophisticated - architectures becomes rapidly unreachable since different subtle mechanisms are likely to - compete. The traditional rationalization proceeds through the use of the well-known Heisenberg - Hamiltonian which introduces effective magnetic coupling constants J. A more sophisticated - approach calls for the participation of anisotropic contributions D and E in a generalized picture. - Even though these phenomenological treatments have turned out to be extremely valuable in a - comprehensive analysis of experimental data, the underlying physical phenomena still deserve - special attention. In particular, how much the respective exchange and anisotropy terms have the - ability to account for such intricate interactions is questionable. Besides, to what extent bridging - ligands remain diamagnetic (innocent) as magnetic interactions between metallic centres are - turned on. Even if such partitioning between physical effects and within magnetic moieties may - not be straightforward, one can think of promising synthetic routes of magnetic systems. - The fdp magnets project we plan to pursue relies on complementary experimental and - theoretical skills. Considering the growing interest for 4f-based materials and their potential - applications, there is a real need for theoretical analysis. Even though some methodologies and - phenomenological approaches are available, DFT as well as ab initio techniques would be - extremely insightful in the understanding of heavy-elements magnetic properties. Our project - combines the synthesis of original and well-characterized prototype objects and the - implementation of demanding calculations. Some architectures of ours are already available for - theoretical inspection. However, specific objects which should hold controlled magnetic - interactions will be prepared in the future to get a thorough understanding of the microscopic - interactions. The association of f, d and p spin carriers within the same molecular objects is a - challenging synthetic target, while understanding their physico-chemistry and more specifically - their magnetic properties is an attractive theoretical problem. - ...

Metabolic profiling has been revolutionized during the last 'post-genomic' decade: several aspects of analytical chemistry, statistics applied to chemistry (i.e. chemometrics), and metabolic biochemistry have merged together to form a new and very dynamic, truly interdisciplinary area of science. Among the scientific areas covered by metabolic profiling methods, metabonomics and metabolomics have independently emerged from distinct disciplinary fields. As a result, the field of metabonomics/metabolomics was ranked fourth out of '10 Emerging technologies' listed in MIT's Technology review in 2005. Biological samples are analyzed by NMR and the spectra are imported in a database. Then the spectral information is summarized in multivariate statistical models such as principal component analysis, linear discriminant analysis or partial least square regressions to derive significant biomarkers associated to the condition under scrutiny. The power of the metabonomic approach lies in the fact that there is no a priori expectation in metabolite level variation, which guarantees a strong potential for biomarker discovery. The bottleneck for advancements in the field of NMR – based metabonomics is twofold: (i) the rarity of metabolic profiling dedicated NMR pulse sequence and (ii) the statistical analysis of NMR data themselves. The objective of this proposal is to develop a metabonomic platform with a new generation of NMR and chemometric tools needed to analyze functional metabolic network data that can be used in functional genomics of model organisms, disease prediction in clinical studies, and therapeutic target discovery in drug development. We have identified specific components of the approach that require development with the following main objectives within: (i) development and optimisation of metabolic profiling oriented NMR pulse programs for analysis of biopsy and biofluid samples, (ii) generation of a pure compound standard database including biologically relevant meta-data (in collaboration with Bruker GmbH), (iii) implementation of state of the art chemometric tools for automated metabolite quantification and pattern recognition models for network and systems biology. We intend to achieve these objectives within the context of the following highly novel biological applications: (i) functional genomics in Caenorhabditis elegans, (ii) screening inborn errors of metabolism in human foetal urine, (iii) diagnosis / prognosis of cancer. The results are expected as follows: development of NMR pulse sequences and chemometric regression models inferring metabolite concentrations in 1H NMR mixture spectra from buifluids and biopsies, using a pure compound standard library, i.e. a spectral dictionary, in collaboration with Bruker GmbH. Different deconvolution and curve resolution approaches will be compared ie, PLS vs. bayesian models (collaboration with University of Oxford). In this context, we expect the increase in spectrometer field strength (initially from 600MHz to 700 MHz then 900 MHz and 1 GHz) to result in: (i) better metabolite concentration inference from 1H NMR mixture spectra, better disease prediction in animal models or human cohorts. Eventually, we will apply network biology visualisation tools based on graph theory. Once reliable concentrations are obtained from NMR spectra, we expect network biology to become the new standard for representing metabonomic data. On the application side, we target: (i) a proof of concept on the use of metabonomics to reveal silent mutations in Caenorhabditis elegans, which would represent a major breakthrough for the C. elegans functional genomics community, because NMR-based metabonomics would provide a cost-effective tool for discovering gene functions, (ii) a high throughput foetal urine screening programme by NMR to provide paediatricians with mechanistic information about disease not routinely available, (iii) a pharmaco-metabonomic study of the effects of growth hormone on cancer cells to develop the potential of very high field NMR for diagnosis and mechanistic purposes.

The aim of the (Sup)3Bases proposal is to study the behaviour of proazaphosphatrane (superbases) in confined medium, i.e. in supramolecular or porous silica materials structures at the nanoscopic scale, involving four different partners at the Laboratoire de Chimie de l'Ecole Normale Supérieure de Lyon holding specific skills to achieve this goal. There is a real challenge to design and characterize such target objects since this is an area where fundamental (synthesis-characterization-electronic structure calculations) and applied (green catalysts, enantioselective chemistry) researches meet. The strength of the (Sup)3Bases project relies on the complementarity of the local expertises. Starting from the synthesis of supramolecular objects and nanostructured porous silica material, superbases will be incorporated to investigate the physical and reactivity changes as confinement occurs. In particular, we will focus on the catalytic activities of these systems in the transformation of triglycerides to Biodiesel and the resolution of racemic alcohols. The strategy will be complemented by ab initio (Density Functional Theory, DFT, and wavefunction based calculations) investigations to rationalize the sought reactivity enhancement. It can be noticed that we have the unique opportunity to gather in a single team all these competences with the different members heterogeneous and homogeneous catalysis, hemicryprophane chemistry, asymmetric synthesis and catalysis and quantum chemical calculations

Sex is used as a mode of reproduction in almost all vertebrate lineages. However, the signals determining if an embryo will develop as a male or a female are generally not conserved between major taxa. Even more surprising are the dramatic differences in evolutionary dynamics observed for sex determination between different groups of vertebrates. For example, mammals and birds have different systems of genetic sex determination, but both systems have been stably maintained over at least 100 million years of evolution in their respective lineages. In contrast, sex determination is extremely variable and evolves very rapidly in fish. Beside different forms of hermaphroditism, almost all possible forms of genetic sex determination have been observed, from male and female heterogamety with or without influence of autosomal loci to more complicated systems involving several loci but without sex chromosomes (polyfactorial sex determination), or several sex chromosomes and even several pairs of sex chromosomes. In numerous species, sex determination can be influenced by temperature and other environmental factors like the pH of the water or even social parameters. In most species, phenotypic sex can be fully reversed by hormone treatment. Importantly, a switch between sex determination systems is frequently observed during evolution in fish. In order to better understand the molecular and evolutionary basis of the diversity of sex determination in fish, the master sex-determining gene(s) -i.e. the gene(s) deciding the sex of individuals, like SRY in mammals- have to be identified in several fish species. So far, the master sex-determining gene has been reported only in the medaka Oryzias latipes. However, this gene, called dmrt1bY, is present in only a very restricted number of species and is therefore not the universal sex-determining gene in fish. Alternative models like the threespine stickleback, tilapia, salmonids and 'our' platyfish are necessary to identify and compare master sex-determining genes and better understand the evolutionary dynamics of sex determination in fish. We have initiated the positional cloning of the sex-determining gene of the platyfish Xiphophorus maculatus, an aquarium fish with many genetic and molecular markers available for the sex chromosomes. A bacterial artificial chromosome (BAC) library of XY males has been constructed and BAC contigs covering about 3 megabases of both X and Y chromosomes have been assembled. Fifty BAC clones covering the sex-determining region have been sequenced and are being assembled and analysed. About 60 sex chromosomal genes have been already identified, ten of them being also present on the mammalian X chromosome. Several new genes not described so far in any organism and with putative functions in sex determination and sex differentiation are particularly under scrutiny. Two ancient gene duplicates organized in tandem are expressed specifically in gonads not only in platyfish but also in medaka and even in Xenopus. Another gene, predominantly expressed in testis, is present at multiple copies of both the X and Y chromosomes of the platyfish. Finally, a last gene called Swimy is present on the Y chromosome in the sex determination region but not on the X, as expected for a male sex-determining gene. While a shorter form of Swimy with putative DNA- and protein interaction domains is expressed almost ubiquitously, a longer form including an additional alternative exon is expressed exclusively in testis. This male-specific protein contains domains potentially involved in posttranslational protein modifications mediated by the peptide SUMO-1. In this project, we propose (i) to finish the analysis of the BAC contigs and the comparison between X and Y chromosomes, with filling in of remaining gaps (ii) to systematically analyse the expression in embryos and adults of sex chromosomal genes not tested so far though RT-PCR and in situ hybridization (iii) to analyse at the functional level through mutant analysis, ectopic expression and knock-down technology the best candidates for a function in sexual development and (iv) to analyse the evolutionary dynamics of sex chromosomes and sex chromosomal genes identified in platyfish, particularly in the context of other systems of sex determination in other species. This project, involving national and international collaborations, will reveal new insights into the evolutionary dynamics of sex chromosomes and sex determination, with the identification a new gene able to control vertebrate sex determination. This study has implications for the aquaculture, where molecular sexing and manipulation of sex determination represent important economical challenges for the control of fish reproduction and growth.