Sur les algorithmes de projections en entropie relative avec contraintes marginales

Cette thèse est centrée autour d'un algorithme de construction de mesures de probabilités à lois marginales prescrites, appelé Iterative Proportional Fitting (IPF). Issu de la statistique, cet algorithme est basé sur des projections successives sur des espaces de probabilités avec la pseudo-distance d'entropie relative de Kullback-Leibler. Cette thèse constitue un panorama des résultats disponibles sur le sujet, et contient quelques extensions et raffinements. La première partie est consacrée à l'étude des projections en entropie relative, à des critères d'existence, d'unicité ainsi que de caractérisation liés à la fermeture d'une somme de sous- espaces. Sous certaines conditions, le problème devient un problème de maximum d'entropie pour des contraintes marginales graphiques. La seconde partie met en avant le procédé itératif IPF. Répondant à l'origine à un problème d'estimation pour les tables de contingence, il constitue plus généralement un analogue d'un algorithme classique de projections alternées sur des espaces de Hilbert. Après avoir présenté les propriétés de l'IPF, on s'intéresse à des résultats de convergence dans le cas fini discret et dans le cas gaussien, ainsi qu'au cas continu à deux marginales, pour lequel une extension est proposée. On traite ensuite plus particulièrement du cas gaussien, pour lequel une nouvelle formulation de l'IPF permet d'obtenir une vitesse de convergence dans le cas à deux marginales prescrites, dont on montre l'optimalité en dimension 2.This work is focused on an algorithm of construction of probability measures with prescribed marginal laws, called Iterative Proportional Fitting (IPF). Deriving from statistical problems, this algorithm is based on successive projections on probability spaces for the relative entropy pseudometric of Kullback Leibler. This thesis consists in a survey of the current results on this subject and gives some extensions and subtleties. The first part deals with the study of projections in relative entropy, namely existence, uniqueness criteria, and characterization properties related to closedness of sumspaces. Under certain assumptions, the problem becomes a problem of maximisation of the entropy for graphical marginal constraints. In the second part, we study the iterative procedure IPF. Introduced initially for an estimation problem on contingency tables, it corresponds in a more general setting to an analogue of a classic algorithm of alternating projections on Hilbert spaces. After presenting the IPF properties, we look for convergence results in the finite discrete case, the Gaussian case, and the more general continuous case with two marginals, for which some extensions are given. Then, the thesis focused on Gaussian case with two prescribed marginal, for which we get a rate of convergence using a new formulation of the IPF. Moreover we prove the optimality for the 2-dimensional case

Advances in the development of Astatine-radiolabelling protocols: exploring the metallic character of astatine

International audiencen.

State-Selective Metabolic Labeling of Cellular Proteins

Transcriptional activity from a specified promoter can provide a useful marker for the physiological state of a cell. Here we introduce a method for selective tagging of proteins made in cells in which specified promoters are active. Tagged proteins can be modified with affinity reagents for enrichment or with fluorescent dyes for visualization. The method allows state-selective analysis of the proteome, whereby proteins synthesized in predetermined physiological states can be identified. The approach is demonstrated by proteome-wide labeling of bacterial proteins upon activation of the P_(BAD) promoter and the SoxRS regulon and provides a basis for analysis of more complex systems including spatially heterogeneous microbial cultures and biofilms

A route for polonium 210 production from alpha-particle irradiated bismuth-209 target

A method is proposed for production of polonium-210 via the 209Bi(α, 3n)210At nuclear reaction. Bombardment of a bismuth-209 target was performed with a 37 MeV alpha-particle beam that leads to the production of astatine-210 (T1/2 = 8.1 h), which decays to polonium-210. It is purified from the bismuth target matrix by employing liquid-liquid extraction using tributyl phosphate (TBP) in para-xylene from 7 M hydrochloric acid. Back extraction of polonium-210 was performed by 9 M nitric acid. This method allows to purify a tracer amount of Po-210 (2.6 * 10-13 mol) from macroscopic amount of Bi (2.8 * 10-2 mol)

Characterization of At- species in simple and biological media by high performance anion exchange chromatography coupled to gamma detector.

Astatine is a rare radioelement belonging to the halogen group. Considering the trace amounts of astatine produced in cyclotrons, its chemistry cannot be evaluated by spectroscopic tools. Analytical tools, provided that they are coupled with a radioactive detection system, may be an alternative way to study its chemistry. In this research work, High Performance Anion Exchange Chromatography (HPAEC) coupled to a gamma detector (γ) was used to evaluate astatine species under reducing conditions. Also, to strengthen the reliability of the experiments, a quantitative analysis using a reactive transport model has been done. The results confirm the existence of one species bearing one negative charge in the pH range 27.5. With respect to the other halogens, its behavior indicates the existence of negative ion, astatide At-. The methodology was successfully applied to the speciation of the astatine in human serum. Under fixed experimental conditions (pH 7.47.5 and redox potential of 250 mV) astatine exists mainly as astatide At- and does not interact with the major serum components. Also, the method might be useful for the in vitro stability assessment of 211At-labelled molecules potentially applicable in nuclear medicine

Cell-selective metabolic labeling of proteins

Metabolic labeling of proteins with the methionine surrogate azidonorleucine can be targeted exclusively to specified cells through expression of a mutant methionyl-tRNA synthetase (MetRS). In complex cellular mixtures, proteins made in cells that express the mutant synthetase can be tagged with affinity reagents (for detection or enrichment) or fluorescent dyes (for imaging). Proteins made in cells that do not express the mutant synthetase are neither labeled nor detected

Biocatalytic reductive amination by native Amine Dehydrogenases to access short chiral alkyl amines and amino alcohols

Small optically active molecules, and more particularly short-chain chiral amines, are key 20 compounds in the chemical industry and precursors of various pharmaceuticals. Their chemo-21 biocatalytic production on a commercial scale is already established, mainly through lipase-22 catalyzed resolutions leading to ChiProsTM products among others. Nevertheless, their 23 biocatalytic synthesis still remains challenging for very short-chain C4 to C5 amines due to low 24 enantiomeric excess. To complement the possibilities recently offered by transaminases, this 25 work describes alternative biocatalytic access using amine dehydrogenases (AmDHs). Without 26 any protein engineering, some of the already described wild-type AmDHs (CfusAmDH, 27 MsmeAmDH, MicroAmDH and MATOUAmDH2) were shown to be efficient for the synthesis 28 of hydroxylated or unfunctionalized small 2-aminoalkanes. Conversions up to 97.1% were 29 reached at 50 mM, and moderate to high enantioselectivities were obtained, especially for (S)-30 1-methoxypropan-2-amine (98.1%), (S)-3-aminobutan-1-ol (99.5%), (3S)-3-aminobutan-2-ol 31 (99.4%) and the small (S)-butan-2-amine (93.6%) with MsmeAmDH. Semi-preparative scale 32 up experiments were successfully performed at 150 mM substrate concentrations for the 33 synthesis of (S)-butan-2-amine and (S)-1-methoxypropan-2-amine, the latter known as “(S)-34 MOIPA”. Modelling studies provided some preliminary results explaining the basis for the 35 challenging discrimination between similarly sized substituents in the active sites of these 36 enzymes

On the move: New insights on the ecology and management of native and alien macrophytes

Globally, freshwater ecosystems are under threat. The main threats come from catchment land-use changes, altered water regimes, eutrophication, invasive species, climate change and combinations of these factors. We need scientific research to respond to these challenges by providing solutions to halt the deterioration and improve the condition of our valuable freshwaters. This requires a good understanding of aquatic ecosystems, and the nature and scale of changes occurring. Macrophytes play a fundamental role in aquatic systems. They are sensitive indicators of ecosystem health, as they are affected by run-off from agricultural, industrial or urban areas. On the other hand, alien macrophytes are increasingly invading aquatic systems all over the world. Improving our knowledge on the ecology and management of both native and alien plants is indispensable to address threats to freshwaters in order to protect and restore aquatic habitats. The International Aquatic Plants Group (IAPG) brings together scientists and practitioners based at universities, research and environmental organisations around the world. The main themes of the 15th symposium 2018 in New Zealand were biodiversity and conservation, management, invasive species, and ecosystem response and restoration. This Virtual Special Issue provides a comprehensive review from the symposium, addressing the ecology of native macrophytes, including those of conservation concern, and highly invasive alien macrophytes, and the implications of management interventions. In this editorial paper, we highlight insights and paradigms on the ecology and management of native and alien macrophytes gathered during the meeting

Glutaredoxin regulation of primary root growth is associated with early drought stress tolerance in pearl millet

Seedling root traits impact plant establishment under challenging environments. Pearl millet is one of the most heat and drought tolerant cereal crops that provides a vital food source across the sub-Saharan Sahel region. Pearl millet’s early root system features a single fast-growing primary root which we hypothesize is an adaptation to the Sahelian climate. Using crop modeling, we demonstrate that early drought stress is an important constraint in agrosystems in the Sahel where pearl millet was domesticated. Furthermore, we show that increased pearl millet primary root growth is correlated with increased early water stress tolerance in field conditions. Genetics including genome-wide association study and quantitative trait loci (QTL) approaches identify genomic regions controlling this key root trait. Combining gene expression data, re-sequencing and re-annotation of one of these genomic regions identified a glutaredoxin-encoding gene PgGRXC9 as the candidate stress resilience root growth regulator. Functional characterization of its closest Arabidopsis homolog AtROXY19 revealed a novel role for this glutaredoxin (GRX) gene clade in regulating cell elongation. In summary, our study suggests a conserved function for GRX genes in conferring root cell elongation and enhancing resilience of pearl millet to its Sahelian environment