Dans le cadre de la loi programme relative à la gestion durable des matières et déchets radioactifs du 28 Juin 2006, la France a choisi comme solution de référence le retraitement de ses combustibles usés et le stockage en milieu géologique profond des déchets ultimes vitrifiés. Néanmoins, les études relatives à un stockage direct des combustibles usés se poursuivent par mesure de précaution. Le concept de stockage prévoit de conditionner les assemblages de combustibles usés dans un surconteneur en acier dont l'étanchéité est garantie sur une durée spécifiée de l'ordre de 10 000 ans. L'arrivée d'eau au contact du combustible après dégradation du conteneur initie les processus de dégradation de la matrice UO2 conduisant au relâchement des radionucléides. Il est de ce fait, important de connaître et de comprendre le mécanisme d’altération de la matrice UO2. Pour cela, des techniques électrochimiques (voltammétries cyclique et linéaire) couplées à des techniques de caractérisation du solide et de la solution (XPS, ICP-MS) ont été utilisées.Une étude thermodynamique et bibliographique du système U(VI)/UO2(s) a permis de mettre en évidence l’influence des conditions physico-chimiques de la solution sur le système, et de mettre en évidence les différents mécanismes proposés pour décrire l’oxydation/dissolution d’UO2 dans différents milieux (non-complexant, carbonaté et argileux). L’étude de l’oxydation/dissolution d’UO2 en milieu acide non-complexant (NaCF3SO3 0,1 mol/L à pH = 3), milieu où le couple UO22+/UO2 prédomine et où la formation de précipités est limitée voire évitée, a mis en évidence un mécanisme en deux étapes électrochimiques et un modèle caractéristique de l’oxydation d’UO2 en milieu acide non-complexant. Ensuite, l’étude en milieu neutre non-complexant (NaCl 0,05 mol/L à pH = 7,5) a mis en évidence un mécanisme en deux étapes électrochimiques et une étape chimique (EEC) dans lequel les deux étapes électrochimiques sont similaires à celles proposées en milieu acide. Enfin, une première approche de l’oxydation/dissolution d’UO2 a été réalisée en milieu carbonaté (NaCl 0,05 mol/L + NaHCO3 2.10-3 mol/L à pH = 7,5) puis en présence d’une phase argileuse (MX80) dans la solution d’étude. Ces études ont respectivement montré l’influence des carbonates et de la MX80 sur la dissolution du dioxyde d’uranium. / Within the framework of the geological disposal of spent nuclear fuel, research on the long term behavior of spent fuel is undertaken and in particular the study of mechanisms of UO2 oxidation and dissolution in water-saturated host rock. Under the law program on the sustainable management of radioactive materials and waste of June 28, 2006, France was chose as the reference solution the retreatment of spent fuel and disposal in deep geological repository of vitrified final waste. Nevertheless, studies on a direct disposal of spent fuel will continue for safety. The disposal concept provides for conditioning spent fuel in a steel container whose seal is guaranteed for a period specified in the order of 10,000 years. It is also reasonable to assume that the groundwater comes into contact with the fuel after the deterioration of container and lead to the UO2 matrix degradation and the release of radionuclides. The oxidation/dissolution of UO2 has been studied by means electrochemical methods coupled to XPS and ICP-MS measurements.A thermodynamic and bibliographic study of U(VI)/UO2(s) system allowed to show the effect of the physical and chemical conditions of the solution on the system, and to show the different mechanisms proposed to describe the oxidation and the dissolution of the uranium dioxide in different media (non-complexing, carbonate and clay). The study of the oxidation/dissolution of UO2 in acidic and non-complexing media (0.1 mol/L NaCF3SO3, pH = 3), where UO22+/UO2(s) predominates and the formation of precipitates is limited or even avoided, showed a mechanism with two electrochemical steps and a model characteristic of UO2 oxidation in acidic non-complexing media. Then, the study in neutral non-complexing media (0.05 mol/L NaCl, pH = 7.5) showed a mechanism with two electrochemical steps and one chemical step (EEC) in which both electrochemical steps are similar to those proposed in acidic media. Finally, a first approach of the UO2 oxidation/dissolution was carried out in carbonate media (0.05 mol/L NaCl + 2x10-3 mol/L NaHCO3, pH = 7.5) and in the presence of clay (MX80) in the solution. These studies have respectively shown the influence of carbonates and MX80 on the dissolution of uranium dioxide.

Ferritins are ubiquitous iron storage proteins in living systems. Although much is known about the iron deposition process in ferritin and a mechanism has been developed, several important issues still remain unknown. One lingering question is the less than stoichiometric quantities of hydrogen peroxide detected in previous studies on animal ferritins. Extensive experimental data on identifying the species in competition for peroxide equivalents point to a surprising conclusion that H2O2 generated in the ferroxidase reaction is consumed by amine buffers that are commonly employed in in vitro ferritin studies, while non-nitrogen containing buffers, such as acetate, phosphate, and carbonate, do not react with H2O2. The effects of amine buffer oxidation on the Fe2+/O2 stoichiometry, the kinetics and the molecular mechanism of iron deposition are discussed. The ~2 nm ferritin shell surrounding the ~4000 Fe(O)OH mineral core was originally thought to isolate the core from the environment. However, synthesized Co- and Mn(O)OH cores in horse spleen and bacteria ferritins are shown to be rapidly reduced by ascorbic acid and horse spleen ferritin containing a reduced Fe(II) core (Fe(II)-HoSF) presumably without direct contact. Further experiments demonstrate that both Fe(II)-HoSF and Co-/Mn-ferritins bind to gold electrodes and exchange electrons through the metallic conductor. These results provide the first direct evidence for electron transfer (ET) through the ferritin shell. The nature of the ET pathway is further investigated by loading iron into native and recombinant ferritins using large oxidants that are too big to enter the ferritin interior and must accept electrons from Fe2+ through this pathway. Experimental results suggest that the endogenous redox center in heteropolymeric animal ferritins and the heme groups in bacteria ferritins mediate ET through the protein shell. Finally, the diffusion properties of ferritin pores are examined toward iron (2+ and 3+) and anion transfer. Iron transfer is studied by the formation of Prussian blue ([FeIIFeIII(CN)6]-) encapsulated in the ferritin cavity, and is consistent with a binding-dissociation model proposed previously for iron transfer through the three-fold channels. When native HoSF is reduced by methyl viologen in saline solutions, small anions such as F-, Cl-, and Br , accumulate in the ferritin interior while phosphate is released. No anion transfer is observed during the reduction of reconstituted HoSF with no phosphate in the core. The possibility of ferritin as an anion pump in vivo is proposed.

This thesis investigates the potential benefits and challenges of using compliant mechanisms in the design of haptic interfaces. The benefits and challenges are presented with an emphasis on their inherent springback behavior and an active compensation approach. Design criteria for compliant mechanism joint candidates are reviewed and several joints are surveyed. Quantitative calculations of axial stiffness and maximum stress for five candidates are presented. Generalized analytical models of springback force and compensation torque are created to simulate the implementation of each joint candidate in a two degree-of-freedom planar pantograph. We use these models in the development and discussion of an analytical approach to predict the motor torques needed to actively compensate for the effects of springback. This approach relies on virtual work analyses of the haptic pantograph to determine the springback forces, compensation torques, haptic workspace, and available haptic force after compensation. A key to estimating the available haptic force is knowing that the force capability is different depending on the local springback force. If a component of the desired haptic force aligns with the springback force, then the two can work together, thus increasing the maximum magnitude of available haptic force beyond the nominal amount. Analytical and experimental results are presented. A detailed method of implementation is given along with a hardware demonstration of active compensation.

This work aims to develop fundamental insights about the underlying surface and bulk chemical processes instrumental to the efficiency of chemical looping combustion (CLC). CLC, which uses a solid-state oxygen carrier (e.g., metal oxides) to drive hydrocarbon combustion, is a promising combustion alternative that minimizes byproduct formation and facilities capture of CO2. In this work, we compare the performance of different transition metal oxides, namely iron, copper, cobalt, manganese, and nickel oxides, as oxygen carriers in CLC using CH4 as the reducing agent. Experiments used a continuous flow reactor across temperatures ranging from 500 to 800 oC and feed flowrates from 12.5 to 250 h-1. In addition to monitoring size-, temperature- and flow rate-dependent performance trends for CH4 conversion to CO2, microscopic and spectroscopic techniques were used to investigate the solid-state mechanism of oxygen carrier reduction and the coupled surface chemical and bulk material processes influencing performance. Bulk (XRD) and surface (XPS) analysis reveal that oxygen carrier reduction can be generally represented by two models, the unreacted shrinking core model (USCM) and the nuclei growth model (NNGM). The reduction of some metal oxides can also proceed via a two-stage solid-state mechanism; for example, hematite reduction to magnetite follows USCM, while the subsequent reductions of magnetite to wustite and wustite to iron metal follow NNGM. Furthermore, our results reveal that minimizing the particle size promotes oxygen carrier performance, but only for metal oxides reduced according to the USCM, where metal oxide reduction initiates on the particle surface. In contrast, no benefit of decreasing particle size was observed for materials reduced according to the NNGM because the reaction initiates in the particle bulk, such that a more critical determinant of reactivity may be the available oxygen carrier volume rather than surface area. Beyond these fundamental insights, cycling experiments were also performed to provide more practical information about the effect of oxygen carrier particle size on their long-term performance in CLC applications.

Antibiotic resistance represents a real threat in the modern world. The problem of resistance is brought about by the fast evolution of bacteria, accelerated by misuse and over-prescription of antibiotics and compounded by the decline in the discovery and development of new classes of antibiotics. Consequently, new targets for antibiotics are in high demand. Flavin-dependent thymidylate synthase (FDTS), which is not present in humans and is responsible for the biosynthesis of a DNA building block in several human pathogens (e.g., M. tuberculosis, B. anthracis, H. pylori), is one such novel target. FDTS catalyzes the reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) to produce 2'-deoxythymidine-5'-monophosphate (dTMP), with N⁵,N¹⁰-methylene-5,6,7,8-tetrahydrofolate (CH₂H₄fol) serving as the carbon source and a nicotinamide cofactor as the electron source. No efficient inhibitors of FDTS are known, despite high-throughput screening attempts to find them. Intermediate and transition-state mimics are likely to bind the enzyme with greater affinity and hence have a better chance at inhibiting FDTS. Therefore, the understanding of the chemical mechanism of FDTS is critical to the informed design of compounds capable of disrupting its function in bacteria. We utilized various techniques, including chemical trapping of reaction intermediates, substrate isotope exchange and stopped-flow, to investigate the FDTS mechanism and determine what sets it apart from other pyrimidine methylases. We found that at least two different intermediates kinetically accumulate in the FDTS-catalyzed reaction. Both of these intermediates are trapped in acid in the form of 5-hydroxymethyl-dUMP, which has never been isolated in other uracil-methylating enzymes. Under basic conditions, however, the earlier intermediate is converted to a species with an unusual flavin-derived adduct, while the later intermediate is converted to dTMP product. Our experiments also suggest that dUMP is activated for the reaction by the reduced flavin - a substrate activation mechanism distinct from the one employed by the classical pyrimidine-methylating enzymes.

The dissolution behavior of a drug substance is an important part of its bioavailability. Three solid dissolution mechanisms are recognized: transport control, interface control and mixed-kinetic control. The mixed-kinetic control mechanism is not well studied as the majority of dissolution phenomena in pharmaceutical research are assumed to be transport-controlled. A phenomenological model for mixed-kinetic control was developed in which the interfacial step comprises molecular detachment and re-deposition and is described by chemical kinetic theory. This model encompasses interface control and transport control as limiting cases. Experimental studies on three organic compounds showed that they dissolved by transport control at 37°C, but exhibited certain degrees of interface control at lower temperatures (10°C and 3°C), which, according to the model, indicates that reducing the dissolution temperature slowed down re-deposition more than transport. Using mathematical approaches derived from the model, up to 27% interface control was calculated from the experimental results. The second experimental investigation showed significant degrees of interface control in benzoic acid dissolution in sodium dodecyl sulfate (NaDS) solutions at 25°C. The dissolution behavior was well described by the mixed-kinetic control model and up to 73% interface control was calculated. An extension of the model was proposed to describe a potential micelle-interface interaction mechanism indicated by the model-fitted parameters. The third investigation showed that FD&C Blue #1, a water-soluble dye, inhibited sulfathiazole dissolution in acidic media but not in water. The inhibition was attributed to the blocking of dissolution sites by dye adsorption. A potential pH-dependent adsorption mechanism was proposed in which protonation at sulfathiazole solid surface gives rise to preferential dye adsorption on detachment rates and thus reduced dissolution rates.

"Catalytic promiscuous" enzymes, which possess additional activities besides their "native" activity, albeit with a lower efficiency than the main reaction, have become a new frontier for biochemistry and have received considerable attention. Catalytic promiscuity has been suggested to contribute to enzyme evolution through the mechanism of gene duplication followed by specialization of one of the two copies for the new function. Mimicking this evolutionary shortcut could also provide a more efficient route to changing the function of proteins by directed evolution. The promiscuous phosphatase PP1 is a member of the phosphoprotein phosphatase (PPP) gene family, which is critical for the control of many cellular pathways by antagonizing the effects of protein phosphorylation mediated by kinases. The catalytic promiscuity of PP1&gamma WT and two mutants has been investigated with a set of monoanionic and dianioic phosphester substrates. PP1&gamma is an effective catalyst for the hydrolysis of both monoanionic and dianionic phosphate-ester based substrates 1-5, with second-order rate accelerations that fall within the narrow range of 1011 to 1013. While the transition states of the uncatalyzed hydrolysis reactions of these substrates differ, those for the PP1&gamma-catalyzed reactions are similar. Thus, the enzyme catalyzes the hydrolysis of these substrates by transition states that are controlled by the active site environment more than by the intrinsic nature of the substrates. The reason for the inability of PP1&gamma to catalyze the hydrolysis of a sulfate ester is unclear, and unexpected, since the charge and transition state of this substrate are well within the range of those of the phosphorus-based substrates that are effectively catalyzed. Inhibition experiments suggest that the PP1&gamma active site is tolerant of variations in the geometry of bound ligands. This characteristic may permit the effective catalysis even of substrates whose steric requirements may result in perturbations to the positioning of the transferring group, both in the initial enzyme-substrate complex and in the transition state. The conservative mutation of arginine 221 to lysine results in a mutant that more effectively catalyzes monoanionic substrates than the native enzyme. The surprising result in substrate preference from a single, conservative mutation lends support to the notion that mutations following gene duplication can result in an altered enzyme with different catalytic capabilities and preferences, and may, following subsequent mutations, provide a pathway for the evolution of new enzymes.

Doctor of Philosophy (PhD) / This thesis aims to establish a sound scientific methodology for the effective and efficient polishing of thermally stable PCD composites (consisting of diamond and SiC) for cutting tools applications. The surface roughness of industrial PCD cutting tools, 0.06 μm Ra is currently achieved by mechanical polishing which is time consuming and costly because it takes about three hours to polish a 12.7 mm diameter PCD surface. An alternative technique, dynamic friction polishing (DFP) which utilizes the thermo-chemical reactions between the PCD surfaces and a catalytic metal disk rotating at high peripheral speed has been comprehensively investigated for highly efficient abrasive-free polishing of PCD composites. A special polishing machine was designed and manufactured in-house to carry out the DFP of PCD composites efficiently and in a controllable manner according to the requirements of DFP. The PCD polishing process and material removal mechanism were comprehensively investigated by using a combination of the various characterization techniques: optical microscopy, SEM and EDX, AFM, XRD, Raman spectroscopy, TEM, STEM and EELS, etc. A theoretical model was developed to predict temperature rise at the interface of the polishing disk and PCD asperities. On-line temperature measurements were carried out to determine subsurface temperatures for a range of polishing conditions. A method was also developed to extrapolate these measured temperatures to the PCD surface, which were compared with the theoretical results. The material removal mechanism was further explored by theoretical study of the interface reactions under these polishing conditions, with particular emphasis on temperature, contact with catalytic metals and polishing environment. Based on the experimental results and theoretical analyses, the material removal mechanism of dynamic friction polishing can be described as follows: conversion of diamond into non-diamond carbon takes place due to the frictional heating and the interaction of diamond with catalyst metal disk; then a part of the transformed material is detached from the PCD surface as it is weakly bonded; another part of the non-diamond carbon oxidizes and escapes as CO or CO2 gas and the rest diffuses into the metal disk. Meanwhile, another component of PCD, SiC also chemically reacted and transformed to amorphous silicon oxide/carbide, which is then mechanically or chemically removed. Finally an attempt was made to optimise the polishing process by investigating the effect of polishing parameters on material removal rate, surface characteristics and cracking /fracture of PCD to achieve the surface roughness requirement. It was found that combining dynamic friction polishing and mechanical abrasive polishing, a very high polishing rate and good quality surface could be obtained. The final surface roughness could be reduced to 50 nm Ra for two types of PCD specimens considered from pre-polishing value of 0.7 or 1.5 μm Ra. The polishing time required was 18 minutes, a ten fold reduction compared with the mechanical abrasive polishing currently used in industry.

Softening deformation of iron ore in the form of sinter, pellet, and lump ore in the cohesive zone of an ironmaking blast furnace is an important phenomenon that has a significant effect on gas permeability and consequently blast furnace production efficiency. The macroscopic softening deformation behavior of the bed and the microscopic deformation behavior of the individual particles in the packed bed are investigated in this study using wax balls to simulate the fused layer behavior of the cohesive zone. The effects of softening temperature, load pressure, and bed composition (mono - single melting particles, including pure or blend particles vs binary ??? two different melting point particles) on softening deformation are examined. The principal findings of this study are: 1. At low softening temperatures, an increase in load pressure increases the deformation rate almost linearly. 2. At higher softening temperatures, an increase in load pressure dramatically increases the deformation rate, and after a certain time there is no more significant change in deformation rate. 3. The bed deformation rate of a mono bed is much greater than that of a binary one. 4. In a binary system, the softening deformation rate increases almost proportionally with the increase in the amount of lower melting point wax balls. 5. In a mono system with blend particles, the content of the lower melting point material has a more significant effect on overall bed deformation than the higher melting point one. 6. The macro softening deformation of the bed behaves the theory of creep deformation. 7. A mathematical model for predicting bed porosity change due to softening deformation based on creep deformation theory has been developed. 8. Increase in load pressure also reduces the peak contact face number of the distribution curves, and this is more prominent with higher porosity values. 9. The contribution of contact face number to bed porosity reduction is more pronounced in a mono system than in a binary system. 10. The porosity reduction in a binary bed is more due to the contact face area increase, presumably of the lower melting point particles. 11. The mono system has a single peak contact face number distribution pattern while the binary system exhibits a bimodal distribution pattern once the higher melting point material starts to deform. 12. In a binary system, an increase in deformation condition severity tends to reduce the contact face number of the higher melting point material without having to increase the contact face number of the lower melting point material accordingly to achieve a given porosity.

Typescript (Photocopy) Includes paper co-authored by the author as attachment. Bibliography: leaves 133-140.