La problématique scientifique de ce travail porte sur le rôle des paramètres de l’alumine sur les évolutions physico-chimiques de matériaux du système CaO-Al2O3. L’objectif de cette étude a donc été d’identifier les paramètres de l’alumine et autres paramètres d’élaboration ayant une influence sur les interactions physico-chimiques au sein d’un système CaO-Al2O3 dans le but d’expliquer et d’optimiser le comportement mécanique de bétons conventionnels réfractaires dans le domaine de température 800-1200°C. Les bétons réfractaires conventionnels sont des composés hétérogènes constitués de granulats d’alumine tabulaire qui jouent le rôle de squelette, liés par une matrice cimentaire, celle-ci étant constituée de clinker et d’alumine fine. Cette zone de température, entre la déshydratation et la céramisation, n’a fait l’objet que de rares études. La méthodologie adoptée, compte tenu de la complexité du matériau béton, a été la fabrication de matériaux « modèles » en voie sèche afin de simplifier et de maîtriser les microstructures, pour prendre en compte l’influence d’un seul paramètre à la fois et établir les relations entre les paramètres d’élaboration, de microstructure et de propriétés mécaniques. La première partie de l’étude a été consacrée à l’étude des propriétés intrinsèques de la phase liante, dans laquelle ont été mis en exergue les paramètres de l’alumine (surface spécifique, morphologie, et impuretés) ayant une influence sur les paramètres microstructuraux permettant une meilleure réactivité et une meilleure tenue mécanique de la matrice cimentaire. La formation de la phase dicalcique CA2 et le degré d’homogénéité du système sont les deux principaux paramètres qui influent sur la tenue mécanique de la matrice cimentaire : le frittage réactif aboutissant à la phase dicalcique contribue notablement à la consolidation du matériau. Il a été montré la réactivité est favorisée par des alumines de grande surface spécifique et contenant des impuretés, comme la silice et la soude. Un modèle statistique prévisionnel a également été mis au point dans le but de prédire le comportement mécanique des matrices cimentaires selon l’alumine choisie. Ces études, confrontées aux résultats issus de la littérature, ont confirmé que les aluminates de calcium se formaient par diffusion des ions Ca2+ vers les alumines à travers les aluminates de calcium riches en chaux.La deuxième partie de cette étude a permis de caractériser les interactions entre matrice cimentaire et granulats d’alumine tabulaire, et de mettre en avant la formation d’interphases entre les deux constituants. Ces interphases sont d’autant plus importantes et cohésives que les matrices cimentaires sont constituées d’alumines fines et impures, enrichies en chaux (même rapport A/C), et de variations dimensionnelles contrôlées. De cette étude, nous avons pu identifier les leviers permettant d’optimiser les propriétés des matériaux du système CaO-Al2O3 dans le domaine de température intermédiaire 800-1200°C. / The scientific problem of this work focuses on the role of alumina parameters on physico-chemical changes of materials of the CaO-Al2O3 system. The objective of this study was to identify the parameters of alumina affecting the physico-chemical interactions within the system CaO-Al2O3 in order to optimize the mechanical behaviour of conventional refractory concrete in the temperature range 800-1200°C. The conventional refractory concretes are composed of heterogeneous aggregates of tabular alumina and a cement matrix, this one consisting of clinker and fine alumina. The temperature zone between dehydration and ceramization is not studied so much in the literature. The methodology adopted, because of the complexity of this kind of materials, has been modelling materials "models" to control the microstructure and to take into account the influence of one parameter at a time and establish relationships between the parameters of development, microstructure and mechanical properties.The first part of this work has studied the intrinsic properties of the binding phase, and has highlighted parameters of alumina (specific surface area, morphology, and impurities) having an influence on the microstructural parameters improving reactivity and mechanical strength of the cement matrix. The CA2 content and the degree of homogeneity of the system are the two main parameters that improve the reactivity of system. A good reactivity of the cement matrix improves this mechanical strength by the effects of microstructure caused by the reactive sintering. It has been shown that these kinds of microstructural parameters are obtained for alumina with high surface area and alumina containing soda or silica. A statistical model has been developed in order to predict the mechanical behaviour of cementitious matrices with the selected alumina. These studies, confronted with results from the literature, confirmed that the calcium aluminates are formed by diffusion of Ca2+ to the alumina through the calcium aluminates rich in lime. The second part of this study highlights the interactions between cement matrix and aggregates of tabular alumina, and put forward the formation of interphases between the two constituents. These interphases are especially significant and cohesive for cementitious matrices composed of alumina rich in silica and soda with a high specific surface area, for lime-enriched matrices (with the same A/C), and for matrices with controlled dimensional variations. In this study, we have identified drivers to optimize the material properties of the system CaO-Al2O3 in the intermediate temperature range 800-1200 °C.

Older age is a primary risk factor for the development of cardiovascular disease in part through the stiffening of the large cardiothoracic elastic arteries (e.g., aorta, carotid arteries). Aging is also associated with reduced cognitive function, cerebrovascular reactivity and brain white matter integrity, but whether these changes in brain structure and function are associated with age-related large artery stiffness remains unclear. In contrast, older adults who have high aerobic fitness demonstrate attenuated large artery stiffness and better cognitive performance compared to their sedentary counterparts, but the effects of aerobic fitness on white matter integrity and cerebrovascular reactivity with aging are conflicting and limited. Moreover, whether high aerobic fitness-associated lower large artery stiffness in older adults is associated with, and perhaps mediates, the beneficial changes in cognitive function and white matter structure remains unknown. The purpose of this study was to investigate the extent to which high aerobic fitness is associated with preserved white matter structure, cerebrovascular reactivity, and cognitive performance in aged individuals, and if these changes in brain structure and function are associated with attenuated large artery stiffness. In young (n=19, 23.6 ± 2.5 years) and old (n=22, 64.4 ± 4.2 years) healthy adults, large elastic artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV, aortic stiffness) via non-invasive applanation tonometry of carotid and femoral pulse waveforms and carotid artery beta-stiffness index (β-stiffness index) and compliance using high-resolution ultrasound and carotid blood pressure via applanation tonometry. Aerobic fitness was measured as maximal exercise oxygen uptake (VO2max) using respiratory gas analysis on an upright cycle ergometer. Older subjects were stratified as high or low fit based on gender and age VO2max classification. Letter, pattern and N-Back cognitive tests were used to assess processing speed and working memory respectively. Fractional anisotropy (FA) from diffusion tensor images and Blood Oxygenation Level Dependent (BOLD) imaging was used to assess cerebrovascular reactivity (CVR) response to a breath hold and brain activation during a working memory task. The association between large artery stiffness and FA was then assessed using a voxel-wise general linear model approach and a region-of-interest analysis. Our results confirmed age-related increases in cfPWV, carotid β-stiffness index and central (carotid) but not brachial systolic blood pressure, and expected reductions in carotid compliance, VO2max, working memory and processing speed, and in white matter integrity in select brain regions (bilateral cingulate, frontal, occipital, temporal). In contrast, we found no age-associated differences in CVR to breath hold stimulus or change in BOLD response to the N-Back. In our cohort of health adults, we found that the age-related changes in large artery stiffness were not attenuated by high compared with low VO2max. Among older adults, large elastic artery stiffness was not associated with regional white matter integrity or cerebrovascular reactivity in any regions-of-interest. Greater carotid artery compliance and lower β-stiffness index was associated with higher processing speed, while compliance was related to higher d'Prime scores and lower reaction time on the 2-Back task among the older adults. CVR to a breath hold stimulus was not related to any measure of cognitive performance. VO2max was not associated with any measures of vascular function, brain structure, function or cognition, indicating relations between large artery stiffness and cognition were independent of aerobic fitness capacity. Taken together, these data suggest that select measures of cognitive performance, but not white matter structure or CVR, may be susceptible to age-related changes in carotid stiffness/compliance and that are unaffected by aerobic fitness. More work is needed to understand the mechanisms by which age-related declines in carotid artery compliance and increased carotid stiffness are associated with reductions in cognitive function in older adults.

Lors d’un freinage aéronautique, les disques en composite C/C constituant les freins sont susceptibles d'être pollués par différentes substances émanant d'éléments de structure de l’avion ou de produits déverglaçants. Ces impuretés, introduites en faible proportion, ont un impact sur les propriétés tribologiques et thermiques des carbones et peuvent être à l’origine d’une usure précoce du frein. Dans cette étude, le nickel, le calcium et le zirconium ont été retenus pour simuler ces contaminants. L’objectif de la thèse fut de déterminer l’influence de la réactivité et de la chimie de surface du substrat sur l’activité de ces additifs. Un graphite Slx50 (Timcal®) a été broyé sous atmosphère contrôlée afin de contrôler sa réactivité. Après l’étape d’imprégnation par différentes solutions salines, les clichés de microscopie électronique en transmission (MET) montrent que la répartition de ces éléments est tributaire de la réactivité du support carboné. La désorption programmée en température couplée à un spectromètre de masse (TPD-MS) a mis en évidence des réactions entre le carbone et ces éléments. La spectrométrie de photoélectrons X (XPS) a permis de compléter l’étude et de proposer un mécanisme réactionnel pour chacun des additifs. / At the moment of aircraft braking, discs in composite C/C constituting the brakes may be polluted by various substances from structural elements of the aircraft or by icing agent products. These impurities introduced in small proportion, have an impact on the tribological and thermal properties of carbon and can be the cause of premature aging of the brake. In this study, nickel, zirconium and calcium were selected to simulate these contaminants. The aim of the thesis was to determine the influence of the reactivity and the surface chemistry of the substrate on the activity of these additives. A graphite Slx50 (Timcal®) was milled under controlled atmosphere in order to control its reactivity. After the impregnation step by various salt solutions, Transmission electron microscopy (TEM) shows that the distribution of these elements is dependent on the reactivity of the carbon support. Temperature Programmed Desorption coupled to Mass Spectrometer (TPD-MS) showed reactions between carbon and these elements. The X-ray Photoelectron Spectroscopy (XPS) allowed to complete the study and to propose a reaction mechanism for each additive.

<p>Cyclobutane pyrimidine dimers (CPD) are the predominant DNA lesions formed upon exposure of this biopolymer to sunlight. Given the potentially dire biological consequences of DNA lesions, there is a need to fully characterize their behaviour, with an eye towards understanding their complete reactivity and as a possible means to detect and quantify their presence in the genome. The work described in this dissertation describes studies of the alkaline reactivity of CPD lesions generated within dinucleotide & polynucleotide strands. It was found that CPD-TpT is generally inert under alkaline conditions at room temperature, which is in agreement with earlier studies on alkaline hydrolysis of CPD-thymine and CPD-thymidine. However, a re-evaluation of the same reaction in the presence of ¹⁸O labelled water demonstrated that, similar to other UV-induced DNA lesions containing a saturated pyrimidine ring, CPD undergoes a water addition at the C4=O group of the nucleobase leading to the formation of a hemiaminal intermediate. This intermediate, however, does not lead to hydrolysis products and completely reverts to starting material under those same conditions. Moreover, the two C4=O groups present on 3′ and 5′-thymines in a CPD molecule show different chemical reactivities, with the 3′ C4=O group having greater affinity towards water addition as compared to the one on 5′ end, a fact reflected in different rates of exchange with the incoming nucleophile leading to the hemiaminal intermediate. The ¹⁸O labelling reaction was also investigated in CPD lesions generated within oligonucleotides to probe the cause of asymmetry between the 3′ <i>vs</i> 5′ C4=O groups; ultimately, it was determined that the asymmetric reactivity observed to occur between the two C4=O groups was an intrinsic property of the CPD molecule and did not arise as a result of asymmetry in a dinucleotide setting.</p><p><br></p> <p>In addition to the above studies, during the course of the investigation of the nucleophilic reactivity of CPD, a chemical reaction was observed leading to what appeared to be the rapid and total chemical reversal of CPD lesions to the original TpT (thymine-thymine dinucleotide)! This “repair” reaction occurred when CPD reacted with hydrazine, and appears facilitated by an inert atmosphere under which it rapidly proceeds to completion at room temperature.</p><br>

Acute viral infections induce CD8 memory T cells that play an important role in the protection of the host upon re-infection with the same pathogen. These virus epitope-specific memory CD8 T cells develop complex TCR repertoires that are specific for that epitope. As individuals age virus-specific immunity appears to wane. Older people have difficulty controlling infection with common viruses such as influenza A (IAV), a RNA virus which causes recurrent infections due to a high rate of genetic mutation, and Epstein Barr virus (EBV), a DNA virus which persists in B cells for life in the 95% of people that become acutely infected. Many factors may contribute to this waning immunity including changes in virus-specific TCR repertoires. We hypothesize that epitope-specific memory CD8 TCR repertoires to these two common viruses change with increasing age and that CD8 T cell cross-reactivity may be one of the mechanisms mediating these changes. To address this hypothesis in our first study, we compared epitope-specific CD8 memory TRBV repertoires directly ex vivo for these two common human viruses. In cross-sectional and longitudinal studies of EBV seropositive, HLA-A2+, young (18-22 years), middle age (25-59 years), and older (>60 years) donors, we demonstrated that CD8 memory TCR repertoires to three immunodominant epitopes, known to have cross-reactive responses, IAV-M158-66, EBV-BM280-288, and EBV-BR109-117 co-evolve as individuals age. Cross-sectional studies showed that IAV-M1-and both EBV-specific repertoires narrowed their TRBV usage by middle-age. In fact, narrowing of EBV-BM and EBV-BR-specific TRBV usage correlated with increasing age. Although narrowing of IAV-M1-specific TRBV did not directly correlate with increasing age there was clear evidence that the TRBV usage was changing with age. The dominant TRBV19 usage appeared to become bimodal in the older age group and interestingly TRBV30 usage did directly correlate with age. For the EBV epitope-specific responses there was preferential usage of particular TRBV and changes in the hierarchy of TRBV usage in the different age groups. Longitudinal studies tracking 3 donors over 10-15 years (middle age to older) showed that there were changes in the TCR repertoire of IAV-M1, EBV-BM and -BR-specific responses over time. In two of the donors who experienced acute IAV infection there was evidence these repertoire changes may be influenced by TCR cross-reactivity, which is enhanced during acute IAV infection. The results of this first ex vivo study are consistent with our hypothesis. They suggest that virus-specific TCR repertoires change over time as an individual ages leading to narrowing of the repertoire and may co-evolve in the presence of CD8 T cell cross-reactivity. To further test our hypothesis in a second study we compared CD8 memory TRAV and TRBV repertoires to the three immunodominant epitopes IAV-M1, EBV-BM, and EBV-BR in the two extreme age groups, young donors (YSP) (18-22 years) and older donors (OSP) (>60 years) using the same donors as in the first study. Since these three epitopes are known to generate cross-reactive CD8 T cell responses and humans during their lifetime are frequently infected with both viruses at the same time these studies were also designed to more closely examine if TCR cross-reactivity could contribute to changes in TCR repertoire with increasing age. We examined the differences in both TRAV and TRBV in these two age groups by monoclonal antibody (mAb) staining and by deep sequencing and single cell sequencing in tetramer positive sorted cells from short-term cultures. Our initial studies showed that there were strong correlations in TRBV usage between short-term cultured and ex vivo antigen-specific responses; functional differences as well as differences in TRBV usage and diversity as measured by mAb staining particularly for the EBV epitope-specific responses between YSP and OSP donors. The TCR deep sequencing data also showed significant differences in TRBV usage between YSP and OSP. However, there were many more differences in TRAV and TRAJ usage than TRBV between the age groups suggesting that TRAV may play a greater role in evolution of the TCR repertoire. With increasing age, there was a preferential selection or retention of TCR for all three epitopes that have features in their CDR3a and b that increase their ease of generation, such as greater usage of convergent recombinant amino acids, and increase cross-reactive potential, such as multiple glycines. YSP and OSP differed in the patterns of TRAV/AJ and TRBV/BJ pairings and usage of dominant CDR3 motifs in all three epitope responses. Both YSP and OSP had cross-reactive responses between these 3 epitopes which were unique and differed from the cognate responses. Analyses of single cell sequencing data suggested that unique combinations of TRAV and TRBV are occurring, where one chain has features consistent with interaction with antigen one and the other chain had features consistent with interaction with antigen two. Interestingly, both the deep sequencing and single cell data show an increased tendency for the classic IAV-M1 specific clone BV19-IRSS-BJ2.7/AV27-CAGGGSQGNLIF-AJ42 to appear among the cross-reactive clones, suggesting that the dominance of this highly public clone may relate to its cross-reactivity with EBV. These results suggest that although OSP and YSP retain some of the classic TCR features for each epitope the TCR repertoire is gradually changing with age retaining TCR that are cross-reactive between these two common human viruses that we are exposed to frequently, one with recurrent infections and the other a persistent virus which frequently reactivates. These results are highly supportive our hypothesis and their importance in relation to viral immune-pathogenesis and potential novel immunotherapies will be discussed. These studies further emphasize the complexity and potential importance of human virus-specific T cell responses and TCR repertoires as people age and the need for a better understanding of TCR cross-reactivity between different viruses. For instance, at the present time these studies are highly relevant to better understanding the immune-pathogenesis observed during the COVID19 pandemic.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第22014号 / 工博第4626号 / 新制||工||1721(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 竹中 幹人 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

This master's thesis was focused on the study of interaction of some organic azo dyes (model diffusion probes) with cationic biopolymer chitosan. This interactions were realized via diffusion processes in hydrogel media based on thermoreversible agarose. The main aim was study of influence of pH of solution on the diffusion process. Interactions of used dyes are based on electrostatic character. The aminogroup of chitosan interacts with the functional group of chosen dyes (anionic sulfonic group) and thus affects the process of diffusion. The model diffusion compounds were chosen organic anionic dyes Chicago sky blue 6B (C.I. 24 410), Sirius red (C.I. 35 780) and Reactive blue 49 (C.I. 621 526). The important content of this diffusion method is a monitoring of the time progression of diffusion profile by UV-VIS spectrophotometry. The presented work follows the bachelor thesis and shows comprehensive view of the reactivity of chitosan and its behavior in different systems. Unsteady diffusion in cuvettes appears to be a universal method for the study of reactivity of biopolymers and for the study of transport processes in hydrogel media. The diffusion method is universal, easy and cheap.

This master thesis deals with the possibilities of traffic of nuclear power unit at thermal and power effect at the end of the campaign, focusing on VVER reactors. For a better idea of the reader the design of key components of the unit in terms of performance is analysed. Parameters of relevant components for Dukovany NPP are presented briefly. The possibilities of traffic of nuclear power unit on thermal and power effect at the end of the campaign are particularly demonstrated on the example of the Dukovany NPP. Furthermore the program Moby-Dick is introduced and the basic possibilities for its use to calculate the course of the campaign are described. At the end of the thesis, we conducted sample calculations for the duration of the campaign on the fourth block of the nuclear power plant.

A series of Fischer mono- and biscarbene complexes of the type [MLn{C=(XR)R'}] was synthesized and characterized. The redox behavior of the complexes was studied by different techniques, including cyclic voltammetry, spectroelectrochemistry, ESR and computational methods. Different transition metals (M) and carbene substituents (XR, R') were employed to compare both the effect of the central metal atom as well as the carbene substituent. Thienyl, furyl and ferrocenyl chromium(0) mono- and biscarbene complexes with ethoxy and amino substituents were electrochemically studied in CH2Cl2. Results were mutually consistent with computational data showing that the carbene double bond of all complexes is reduced pseudo reversibly to an anion radical, -Cr-C•. The Cr centers are oxidized in two successive one electron transfer steps to Cr(II) via the Cr(I) intermediate. For all ferrocenyl carbene complexes the Fe(II) is oxidized after the first oxidation of Cr. It was found that with respect to the aryl substituents the donating effect decreases from Fc>Fu>Th. Stabilization from the XR substituent, where XR = NHR, also resulted in lower redox potentials compared to their OEt analogues. The inclusion of ferrocene in the carbene substituent was done, as its redox activity and increased donating effect are well known. Mono- and biscarbene complexes with ethoxy and amino substituents of both chromium and tungsten were electrochemically studied. Again experimental data were supported by computational studies. Similar to the ethoxy chromium complexes, reduction of the W=C fragment to -W-C• was observed. However oxidation of the Fc group occurred first before the electrochemically irreversible oxidation process for W(0) involving a three electron-mediated process as seen in chronocoulometric analyses. The tungsten oxidation was restricted to a W0/II, consistent with computational studies, by the use of the electrolyte [NnBu4][B(C6F5)4]. The short-lived W(II) species were calculated to be stabilized by agostic CH···W interactions, similar to the chromium analogues. To extend linkers between the metal-carbene termini and investigate metal-metal interaction, biferrocenyl and 2,5-thienylbiferrocenyl tungsten(0) mono-and biscarbene complexes were synthesized and studied by spectroelectrochemistry. A metal-metal charge transfer transition between the tungsten carbonyl increment and the biferrocenyl / 2,5-thienylbiferrocenyl unit was confirmed by infrared spectroelectrochemical studies. The electronic interaction in the corresponding cationic species can be described as weakly coupled class II systems according to Robin and Day. The cymantrenyl moiety, Mn(η5-C5H4)(CO)3, provides an interesting alternative to ferrocene as an organometallic molecular tag, however the instability of the radical cation impairs its use. Improved stability of the cation, monitored by electrochemical measurements, was accomplished by substituting a carbonyl with a ferrocenyl Fischer carbene ligand resulting in Mn(I) oxidation occuring at lower potentials than ferrocenyl oxidation. These uncommon Fischer carbene complexes is the first organometallic multi-tags reported. The mono cationic species, [CpMn(CO)2{=C(OEt)Fc}][PF6], could be isolated and characterized with ESR analysis. Finally, transmetallation from the tungsten(0) Fischer carbene complexes yielded examples of rare acyclic alkoxy- and aminocarbene complexes of gold(I). Single x-ray structures for all complexes could be obtained including the novel ferrocenophane dinuclear biscarbene Au(I) complex. All structures display unsupported aurophilic interactions, while the bridging biscarbene shows a semi-supported Au-Au interaction. In the case of the furanyl/thienyl methoxy monocarbene complexes, extended Au-Au interactions result in oligomeric structures. Although this study is of a fundamental nature, it is imperative for the understanding and design of gold compounds with specific applications. / Thesis (PhD)--University of Pretoria, 2013. / gm2014 / Chemistry / unrestricted

Les recherches présentées dans ce manuscrit s’articulent autour de deux parties distinctes. La première partie concerne une étude mécanistique de la réaction de décomposition de l’acide formique (AF) photocatalysé par le Tetra-n-ButylAmmonium DecaTungstate (TBADT) et explore la réactivité de ce photocatalyseur envers l’AF. La deuxième partie de ces travaux se focalise sur l’étude de la réactivité radicalaire d’anions phosphorés et de leurs analogues chalcogénés. Dans un premier temps, nous nous sommes intéressés à exploiter la réactivité de phosphures-borane et des anions d’oxydes de phosphine pour la formation de liaisons C-P par photo-induction dans le visible. Dans un second temps, nous avons exploré la réactivité radicalaire et ionique des phosphures-borane chalcogénés, par une étude de leur structure et de leur réactivité. Ces propriétés ont été mises en application dans le cadre de réactions de photo-polymérisation radicalaire et de réduction de composés électrophiles. / This dissertation is organized in two distinct parts. The first one is a mechanistic investigation of the photocatalyzed reaction of decomposition of formic acid (AF) under mild conditions using Tetra-n-ButylAmmonium DecaTungstate (TBADT). The second part of this work revolve around the use and study of the radical reactivity of phosphorous anions and their chalcogenated analogues. Firstly, we used the radical reactivity of phosphido-borane and phosphine oxide anions for the formation of C-P bonds. In a last part, we explored the radical and ionic reactivity of chalcogenated phosphido-borane, by studying their structure and reactivity. These properties has been applied to radical photo-polymerization reactions and for the reduction of electrophiles.