Bacteria of the genus Bartonella infect the red blood cells of a wide range of wild and domestic mammals and are transmitted between hosts by blood-sucking insects. Although most Bartonella infections are asymptomatic, the genus contains several human pathogens. In this work, host adaptation and host switches in Bartonella have been studied from a genomic perspective, with special focus on the acquisition and evolution of genes involved in host interactions. As part of this study, the complete genome of B. grahamii isolated from a Swedish wood mouse was sequenced. A genus-wide comparison revealed that rodent-associated Bartonella species, which have rarely been associated with human disease, have the largest genomes and the largest number of host-adaptability genes. Analysis of known and putative genes for host interactions identified several families of autotransporters as horizontally transferred to the Bartonella ancestor, with a possible role both during early host adaptation and subsequent host shifts. In B. grahamii, the association of a gene transfer agent (GTA) and phage-derived run-off replication of a large genomic segment was demonstrated for the first time. Among all acquisitions to the Bartonella ancestor, the only well conserved gene clusters are those that encode the GTA and contain the origin of the run-off replication. This conservation, along with a high density of host-adaptability genes in the amplified region suggest that the GTA provides a strong selective advantage, possibly by increasing recombination frequencies of host-adaptability genes, thereby facilitating evasion of the host immune system and colonization of new hosts. B. grahamii displays stronger geographic pattern and higher recombination frequencies than the cat-associated B. henselae, probably caused by different lifestyles and/or population sizes of the hosts. The genomic diversity of B. grahamii is markedly lower in Europe and North America than in Asia, possibly an effect of reduced host variability in these areas following the latest ice age.

This thesis presents the results of the investigation on developing and evaluating a low temperature (<150oC) non - catalytic process using a hydrogen transfer agent (instead of molecu-lar hydrogen) for coal dissolution in supercritical CO2. The main idea behind the thesis was that one hydrogen atom from water and one hydrogen atom from the hydrogen transfer agent (HTA) were used to hydrogenate the coal. The products of coal dissolution were non-polar and polar while the supercritical CO2, which enhanced the rates of hydrogenation and dissolution of the non-polar molecules and removal from the reaction site, was non-polar. The polar modifier (PM) for CO2 was added to the freed to aid in the dissolution and removal of the polar components. The addition of a phase transfer agent (PTA) allowed a seamless transport of the ions and by-product between the aqueous and organic phases. DDAB, used as the PTA, is an effective phase transfer catalyst and showed enhancement to the coal dissolution process. COAL + DH- +H2O  COAL.H2 + DHO-- This process has a great feature due to the fact that the chemicals were obtained without requir-ing to first convert coal to CO and H2 units as in indirect coal liquefaction. The experiments were conducted in a unique reactor set up that can be connected through two lines. one line to feed the reactor with supercritical CO2 and the other connected to gas chromatograph. The use of the supercritical CO2 enhanced the solvent option due to the chemical extraction, in addition to the low environmental impact and energy cost. In this thesis the experiment were conducted at five different temperatures from atmos-pheric to 140°C, 3000 - 6000 psi with five component of feed mixture, namely water, HTA, PTA, coal, and PM in semi batch vessels reactor system with a volume of 100 mL. The results show that the chemicals were obtained without requiring to first convert coal to CO and H2 units as in indirect coal liquefaction. The results show that the conversion was found to be 91.8% at opti-mum feed mixtures values of 3, 1.0 and 5.4 for water: PM, HTA: coal, water: coal respectively. With the oil price increase and growing in energy demand, the coal liquefaction remain afforda-ble and available energy alternative.

No description available.

This thesis focuses on the genomic study of symbionts of two different groups of hymenopterans: bees and ants. Both groups of insects have major ecological impact, and investigating their microbiomes increases our understanding of their health, diversity and evolution. The study of the bee gut microbiome, including members of Lactobacillus and Bifidobacterium, revealed genomic processes related to the adaptation to the gut environment, such as the expansion of genes for carbohydrate metabolism and the acquisition of genes for interaction with the host. A broader genomic study of these genera demonstrated that some lineages evolve under strong and opposite substitution biases, leading to extreme GC content values. A comparison of codon usage patterns in these groups revealed ongoing shifts of optimal codons. In a separate study we analysed the genomes of several strains of Lactobacillus kunkeei, which inhabits the honey stomach of bees but is not found in their gut. We observed signatures of genome reduction and suggested candidate genes for host-interaction processes. We discovered a novel type of genome architecture where genes for metabolic functions are located in one half of the genome, whereas genes for information processes are located in the other half. This genome organization was also found in other Lactobacillus species, indicating that it was an ancestral feature that has since been retained. We suggest mechanisms and selective forces that may cause the observed organization, and describe processes leading to its loss in several lineages independently. We also studied the genome of a species of Rhizobiales bacteria found in ants. We discuss its metabolic capabilities and suggest scenarios for how it may affect the ants’ lifestyle. This genome contained a region with homology to the Bartonella gene transfer agent (GTA), which is a domesticated bacteriophage used to transfer bacterial DNA between cells. We propose that its unique behaviour as a specialist GTA, preferentially transferring host-interaction factors, originated from a generalist GTA that transferred random segments of chromosomal DNA. These bioinformatic analyses of previously uncharacterized bacterial lineages have increased our understanding of their physiology and evolution and provided answers to old and new questions in fundamental microbiology.

Résumé confidentiel / Résumé confidentiel

Le polyéthylène (PE) est omniprésent dans notre vie de tous les jours et ce principalement car il présente des propriétés thermiques et mécaniques qu’on ne retrouve pas d’autres polymères. Cependant, sa très faible réactivité chimique fait qu’il est difficile de l’incorporer dans des architectures macromoléculaires plus complexes qui pourraient profiter de ses propriétés uniques. La modification de polymères fonctionnels en extrémité de chaîne par des réactions de couplage efficaces est un outil très utilisé pour la conception d’architectures macromoléculaires. Parmi les différentes réactions envisageables, la réaction de cyclo-addition 1,3 dipolaire de Huisgen entre un azoture et un alcyne est très utilisée dans le domaine de la science des polymères pour lier des polymères entre eux. Une autre méthode performante est le couplage par une réaction d’addition de type hétéro Diels-Alder (HDA) entre un diène et un dithioformate. L’objectif de ce travail de thèse est dans un premier temps d’identifier un système de polymérisation catalytique de l’éthylène qui permette de synthétiser du polyéthylène de masse molaire variable et comportant à une extrémité une fonction réactive. Puis cette extrémité réactive est mise à profit dans des réactions de couplage efficaces comme celles mentionnées plus haut pour la synthèse d’architectures macromoléculaires incorporant des segments de PE / Polyethylene (PE) is a polymer of great importance in our everyday life due to its unique thermal and mechanical properties. However, it suffers from lack of reactivity that prevents to introduce it into more complexed architectures the final properties of which would benefit from these unique features. The modification of end-functionalized polymers through orthogonal and efficient coupling reactions is a powerful and widely used tool for the design of various macromolecular architectures. In today’s polymer science the copper catalyzed azide-alkyne cycloaddition (CuAAC) is the most frequently used « click » reaction. Another efficient coupling method is the hetero Diels-Alder (HDA) reaction between a diene end-functionalized polymer and the electron deficient dithioester end-group of a polymer synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization. Our first aim was to fin and optimize the best ethylene catalytic polymerization system that would allow to produce PE with different molar masses and end functional groups. In a second step, we tried to introduce polyethylene segments in macromolecular architectures by taking advantage of the best attributes of the aforementioned coupling reactions

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第21963号 / 工博第4618号 / 新制||工||1720(附属図書館) / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 山子 茂, 教授 辻井 敬亘, 教授 大内 誠 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

本研究主要是對上海的技術中介機構和資產評估事務所作初探性的研究，希望去實地瞭解目前中國大陸上海技術交易市場運作的狀況，及其技術鑑價相關機構。 　　在技術交易市場平台中有許多環節，本研究將著重於探討上海技術交易中介機構及其技術鑑價體系的運作情形，並瞭解其對於技術交易風險是否有機制去降低它；另一方面，也對其技術交易中的技術鑑價體系作深入的了解，包括其成立的背景、運作狀況及其使用之鑑價方法和程序為何。 　　訪談和資料收集後發現，中國大陸技術市場所扮演的角色主要為：溝通、評估、協調、組織。中國政府近年來大力推動技術交易、技術產權交易，配合各種優惠政策吸引技術、人才和資金，所以技術市場發展迅速蓬勃。評估的部分，技術鑑價為其資產評估的一部份，但是由於過去政治體制的影響，受限法令，流於形式，發展有限。主要技術成交價格由市場去決定。對於欲交易的技術的真實性與可靠性，有作初步的確認，但受限資源，並無法作深入的瞭解和把關，由欲購買技術者與技術賣方接觸詳談瞭解。 / In Mainland China, the government is promoting the “technology market” in order to push the technology into the market these years. The “technology market”, including STTE, Saviaq and technology transfer agent office, is a platform for technology transfer and exchange. This research surveys these intermediary organizations of technology transfer and exchange, and the technology evaluation organization in Shanghai. By visiting the STTE (Shanghai Technical Transfer Exchanger), Saviaq, Ke-Hua asset evaluation office and technology transfer agent office, this research wants to know how this platform work, and focuses on how they evaluate the technology and how these organizations work, the background of these organizations established and if the platform has the risk free prevent process in the dealing of technology transfer and exchange or not. 　　In Mainland China, the main function of “technology market” is offering an information platform of technology transfer and exchange. The Saviaq and STTE combine with many preferential treatment policies for pulling in the capital and the high educated people with the working experience in high technology industry. 　　The “technology market” in Mainland China is growing rapidly recently. This platform has four main functions: communication between the investors and the technology owner, evaluation of the technology, corresponding with the dealers, organizing and makes some activities to promote the technology transfer and exchange. 　　The technology evaluation is one part of capital evaluation. Because the political background of communism, the development of the capital evaluation industry is limited by the old government system and laws. The evaluation has no efficient for the dealer in the real market, it just a legal process of the technology transfer and exchange. The final price of the technology transfer and exchange is decided by the dealing. 　　About the evaluation and risk free prevent process of the technology transfer and exchange is not very sufficient. The “technology market” just does the simple identification of the reality of the technology because identifying the reality need profession and much manpower, but the resource is limited. The “technology market” is just a platform which offers the deal information to the members of their organization. The people can find the technology which they want to invest, and they can make detailed evaluation by themselves.

L'objectif de cette étude est de développer une méthodologie permettant de déterminer et de mettre en \oe{}uvre les conditions opératoires optimales du procédé fed-batch de copolymérisation en émulsion du styrène et de l'acrylate de butyle en présence d'un agent de transfert de chaîne (CTA). Elle vise particulièrement à optimiser la production et les caractéristiques physico-chimiques de particules de latex à propriétés d'usage ciblées. Après une étude expérimentale de l'impact des différents facteurs, le modèle mathématique du procédé a été développé traduisant l'effet particulier de l'agent de transfert de chaîne sur la cinétique de polymérisation et mettant l'accent sur une les bilans de population. Une approche basée sur l'analyse de l'estimabilité des paramètres a ensuite permis de sélectionner 21 paramètres parmi les 49 paramètres du modèle mathématique dont les valeurs ont été identifiées grâce à un algorithme génétique. Le modèle mathématique validé en modes batch et fed-batch a ensuite été exploité pour l'optimisation multicritère du procédé orientée vers la maximisation de la production de particules de latex possédant une morphologie de type coeur-écorce avec un profil de température de transition vitreuse prédéfini. L'ensemble des solutions du front de Pareto a été obtenu grâce à un algorithme évolutionnaire développé et testé à cet effet. La meilleure alternative obtenue grâce à un outil d'aide à la décision a été implémentée expérimentalement et comparée avec succès aux prédictions du modèle mathématique / The objective of this study is to develop a methodology in order to determine and implement the optimal operating conditions of the emulsion fed-batch copolymerization process of styrene and butyl acrylate in the presence of a chain transfer agent. It particularly aims to optimize the production and the physico-chemical characteristics of latex particles with targeted end-use properties. After an experimental study, the process model has been developed taking into account the particular effect of the chain transfer agent on the polymerization kinetic and highlights the population balance. Thanks to an estimability analysis approach, 21 parameters among the 49 parameters of the model have been selected whose values have been identified by using a genetic algorithm. The mathematical model validated in both batch and fed-batch modes was then exploited for the multicriteria optimization of the process oriented towards the maximization of the production of latex particles having a core-shell type morphology with a given glass transition temperature profile. The Pareto's front solutions were obtained thanks to an evolutionary algorithm developed and tested for this purpose. The best alternative obtained by a decision-making aid tool was finally experimentally implemented and successfully compared with the predictions of the mathematical model

Ce projet de thèse consistait à synthétiser de nouveaux bio-conjugués Lipide-Polymère fluorescents émettant dans le rouge lointain, composés d’une chaîne polymère portant à la fois de nombreux chromophores en position latérale et un lipide en extrémité de chaîne. La structure de ces bio-conjugués est basée sur des copolymères poly(N-acryloylmorpholine-co-N-acryloxysuccinimide), hydrophiles, réactifs, modulables et d’architecture contrôlée obtenus par le procédé RAFT. Les copolymères réactifs ont ensuite été utilisés pour le couplage, en position latérale, de chromophores émettant dans le rouge lointain. La stratégie utilisée pour la synthèse des bio-conjugués se divise en trois étapes : la synthèse d’Agents de Transfert de Chaîne (ATC) fonctionnalisés avec un lipide suivant un protocole déjà décrit suite à des travaux de notre équipe, et dont les étapes de purification ont été améliorées afin d’obtenir des ATC les plus purs possible (90% de pureté molaire) ; l’utilisation de ces ATC fonctionnels pour la synthèse de polymères α fonctionnels, et enfin, le couplage covalent, rapide et efficace, de chromophores en position latérale. Il a été mis en évidence que les ATC lipidiques permettent un très bon contrôle de la copolymérisation des monomères NAM et NAS. L’utilisation de la composition azéotropique pour ce couple de monomère permet également d’obtenir des chaînes polymère de microstructure très contrôlée et présentant des valeurs de Mn comprises entre 5 900 et 33 200 g.mol-1. Les propriétés optiques des bio-conjugués ont été déterminées, ce qui a permis de mettre en évidence que ces propriétés, et notamment le rendement quantique de fluorescence, sont très sensibles à la structure des bio-conjugués synthétisés. Tous les bio-conjugués présentent des brillances améliorées (jusqu’à 13 000 M-1.cm-1 dans l’eau et 50 0000 M-1.cm-1 dans CHCl3) par rapport à celle du chromophore. La capacité des bio-conjugués à interagir avec les bicouches lipidiques a été mise en évidence à travers l’utilisation de systèmes modèles (SUVs, LUVs et GUVs). Enfin, les évaluations biologiques réalisées ont montré à la fois une absence de cytotoxicité des bio-conjugués et une capacité de ces derniers à être internalisés rapidement (< 10 min) au sein de différentes lignées de cellules vivantes. / The aim of this study is to synthesize new far-red emitting fluorescent Lipid-Polymer conjugates, consisting of a polymer chain bearing both multiple fluorophores in lateral position and a lipid at one chain-end. These conjugates are based on an hydrophilic, reactive, flexible and controlled poly(N-acryloylmorpholine-co-N-acryloxysuccinimide) copolymer synthesized by the RAFT process. Multiple far-red emitting fluorophores were bound on the reactive copolymer in lateral position. The strategy used in this study consists of three different steps: Chain Transfer Agents (CTA) functionalized with a lipid were synthesized following a protocol already described in our team, the purity of these CTA was improved (90% molar purity); the use of these CTA for the synthesis of α functional polymers, and finally, the very efficient covalent binding of fluorophores in lateral position. We showed that the lipid-CTA enable a very good control of the NAM/NAS copolymerization. The azeotropic composition enables the synthesis of polymer chains with a controlled composition and with Mn values varying from 5 900 to 33 200 g.mol-1. The optical properties of the bio-conjugates were determined, and we showed that these properties (the fluorescence quantum yield especially) are structure sensitive. All of them show an improved brightness (13 000 M-1.cm-1 in water and 50 000 M-1.cm-1 in CHCl3) compared to the brightness of the free fluorophore. The ability of the bio-conjugates to interact with lipid bilayers was proved using model systems (SUVs, LUVs and GUVs). Finally, biological evaluations showed both an absence of cytotoxicity and an ability of the conjugates to be quickly internalized in leaving cells (< 10 min).