Pour améliorer les paramètres pharmacologiques d'un photosensibilisateur de seconde génération, la méta-tétra(hydroxyphényl)chlorine (mTHPC), plusieurs formules liposomales commerciales ont été élaborées, parmi elles le Foslip, qui correspond à la mTHPC dans des liposomes conventionnels. L'objectif de ce travail est d'étudier les caractéristiques photophysiques et photobiologiques du Foslip.<br />L'exposition des suspensions de Foslip à de petites doses de lumière (10 mJ) a conduit à une baisse significative de la fluorescence, qui a cependant été restaurée après destruction des liposomes. Nous attribuons cette caractéristique au quenching de fluorescence photoinduite. Cet effet a été mis en évidence uniquement pour les concentrations locales élevées de mTHPC dans des bicouches lipidiques. Les résultats ont été interprétés en supposant une migration d'énergie entre les molécules rapprochées de mTHPC avec sa dissipation consécutive par les molécules du photoproduit se comportant comme des pièges d'énergie. Le quenching de fluorescence photoinduite ainsi que les techniques de polarisation et de chromatographie liquide ont été appliquées successivement pour estimer le taux de redistribution des molécules de mTHPC des liposomes vers les protéines du plasma et les membranes lipidiques. Les processus de redistribution de la mTHPC après injection intratumorale de mTHPC dans un modèle de récidive de cancer du sein sont en corrélation avec les résultats obtenus dans une étude in vitro de la redistribution du Foslip dans les liposomes DPPC. Il a été démontré que le phénomène de quenching de fluorescence photoinduite doit être pris en compte lors de l'utilisation de techniques optiques pour l'étude des applications in vivo et in vitro des formulations liposomales de mTHPC.

This thesis focuses on the numerical and theoretical studies of gas quenching in industrial furnaces. Gas quenching is the rapid cooling of metal pieces, aiming at forcing a phase transformation of the metal structure to improve its mechanical properties. The numerical methodology has been evaluated with respect to the desired accuracy and different aspects of the flow with importance for achieving an optimized process have been investigated. Initially, attention was paid to the flow and heat transfer fields both in an empty furnace and in a furnace loaded with different charges with the objective to study the influence of the charge configuration on the flow and heat transfer uniformity. This study led to the identification of several possible improvements, which are currently being implemented by the industrial partners of this project. As earlier studies had shown the importance of flow uniformity on the quality of the heat treatment, the subsequent work focused substantially on the flow uniformity upstream of the quenching zone resulting in design recommendations for the particular type of furnace under consideration. The dependence of the performance of the coolant medium on its composition was investigated theoretically and an analysis of most important parameters was carried out. Improved knowledge of the effect of gas mixture composition on heat transfer was added to the body of knowledge already available. / QC 20101019

This thesis focuses on investigations of transient dark states of fluorescentmolecules using spectroscopic techniques. The main purpose is to show andconvince the reader that transient dark states are not always a nuisance, butalso represent an additional source of information. Several studies with fluorescencecorrelation spectroscopy were performed, all related to non-fluorescentstates such as triplet state or isomerized states.Photobleaching is one of the main problems in virtually all of the fluorescencetechniques. In this thesis, mechanisms that retard photobleaching arecharacterized. Several compounds, antioxidants and triplet state quenchers,which decrease photobleaching, are studied, and guidelines for achieving optimalfluorescence brightness using these compounds are presented.Triplet state quenching by several compounds was studied. Detailed investigationsof the fluorescence quencher potassium iodide demonstratedthat for some of fluorophores, except of quenching, there is fluorescence enhancementmechanism present. In agreement with the first publication inthis thesis, antioxidative properties were found to play an important role inthe fluorescence enhancement. Quenching of the triplet state is proposedas a tool for monitoring diffusion mediated reactions over a wide range offrequencies.Specially designed fluorophores combining high triplet yields with reasonablefluorescence brightness and photostability were characterized forpossible applications in novel super-resolution imaging techniques based onfluorescence photoswitching. Except of benefits for imaging techniques, photoinducedswitching to non-fluorescent states could be used for monitoringmolecular diffusion, which was also demonstrated in this thesis.Studies of the triplet state kinetics of fluorophores close to dielectric interfaceswere performed using fluorescence spectroscopy. The analysis of thetriplet state kinetic can provide information about the local microenvironmentand electrostatic interactions near dielectric interfaces. / QC 20100414

Hot forming of boron steels is becoming increasingly popular in the automotive industry due to the demands for weight reduction and increased safety requirements for new vehicles. Hot formed components offer a significant increase in strength over conventional cold-formed steels, which has allowed for reductions in material thickness (and thus weight) while maintaining the same strength. Hot formed components are typically used in structural applications to improve the integrity of the vehicle’s cabin in the event of a collision. It has been suggested, however, that the crash performance of certain hot formed parts may be increased by locally tailoring their mechanical properties to improve their energy absorption. The final microstructure of a hot formed part is driven by the rate at which it is cooled within the tooling during the forming and quenching process. By controlling the cooling rate of the part, it is possible to control the final microstructure, and thus the final mechanical properties. This thesis outlines the experimental and numerical studies that were performed for the hot forming of a lab-scale B-pillar. A hot forming die set was developed which has both heating and cooling capabilities to control the local cooling rate of the blank as it is formed and quenched. The first aspect of this research is to produce a hot formed part which is representative of an industrial component, and then to numerically model the process to predict the final mechanical properties. The second aspect is to produce a hot formed part with tailored mechanical properties, such that there are regions of the part with very high strength (very hard) and other regions with increased ductility (softer). By tailoring the microstructure to meet the performance requirement of a hot formed part, it may be possible to optimize its crash behavior and also reduce the overall weight. Cartridge heaters were installed into sections of the tooling allowing it to reach a maximum temperature of 400°C. Cooling channels are used in other sections to maintain it at approximately room temperature. Experiments were performed on 1.2 mm Usibor® 1500P steel at heated die temperatures ranging from 25°C to 400°C. In the fully cooled region, the Vickers hardness of the blank was measured to be 450 – 475 HV, on average. As the temperature of the heated region was increased, a significant softening trend was observed in the areas of the blank that were in contact with the heated tool. The greatest levels of softening occurred in the 400°C heated die trial. Hardness measurements as low as 234 HV were recorded, which represents a reduction in hardness of 49% compared to the fully cooled trials. Numerical models of the experiments were developed using LS-DYNA and use of its advanced hot forming material model which allows for microstructure and hardness prediction within the final part. The numerical models have shown promising results in terms of predicting the hardness trends as the temperature of the die increases. Thermal expansion of the tooling resulted in local changes in the geometry of the tooling which proved to be problematic during the forming and quenching stages of the process. The expansion caused unexpected changes in the part-die contact, and the resulting microstructures were altered. These thermal expansion issues were addressed in the current work by shimming the tooling; however, in future work the tooling should be designed to account for this expansion at the desired operating temperature.

The primary goals of our research are to understand the virology and enzymology of human T-cell leukemia virus type I (HTLV-I) that will lead to the development of treatments for patients infected with HTLV-I. HTLV-I is an oncogenic virus of the Retroviridae family and is the causative agent of adult T-cell leukemia/lymphoma (ATL), tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM). HTLV-I has been classified as a dangerous emerging pathogen by the Centers for Disease Control and Prevention with at least 20 million people infected with the virus. This is a significant problem because there are currently no effective treatments to control HTLV-I infection and prevent or treat HTLV-I induced ATL and TSP/HAM. The protease is necessary for retroviral maturation and replication and is, therefore, an attractive target for inhibitor design. Investigation of peptide mimetic compounds incorporating the tetrahedral intermediate of aspartyl protease catalyzed cleavage are crucial for the development of lead inhibitors. Compounds containing statine, 4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA), or hydroxyethylamine (HEA) are presented in this work. The best compound was a statine-based inhibitor, which had a Ki = 29 +/- 4 nM and 88% inhibition against an HTLV-I protease native substrate in a FRET assay.

This aim of this thesis is to examine the possibility of using Magnetic Barkhausen Noise (MBN) technique in characterizing the microstructures of quenched and tempered low alloy steels as well as annealed low carbon steels. To determine the average grain size by MBN, SAE 1010 steel consisting of dominantly ferrite was used. The specimens were slowly cooled in the furnace after austenitizing at different time and temperature variations. By metallographic examination the average ferrite grain size of specimens was determined. The magnetic parameters were measured by a commercial MBN system. With increasing ferrite grain size, the magnetic Barkhausen jumps caused by the microstructure were decreased due to the reduction in grain boundary density per unit volume. A clear relationship has been observed between average grain size and the magnetic Barkhausen noise signals. SAE 4140, 5140 and 1040 steels were used to characterize the microstructures of quenched and tempered specimens. After austenitizing and quenching identically, the specimens were tempered at various temperatures between 200oC and 600oC. Formation of the desired microstructures was ensured by metallographic examinations and hardness measurements. The results show that as tempering temperature increases the Barkhausen activity increases due to the enhancement of domain wall displacement with softening of the martensite. It has been shown that MBN is a powerful tool for evaluating the microstructures of martensitic and annealed steels.

In the course of thermal treatments, materials are usually subjected to continuous heating and cooling cycles during which microstructural evolution and mechanical interactions occur simultaneously at different length and time scales. Modeling of these processes necessitates dealing with inherent complexities such as large material property variations, complex couplings and boundary conditions, coupled heat and mass transfer mechanisms and phase transformations. In this study, a mathematical framework based on finite element method (FEM) capable of predicting temperature history, evolution of phases and internal stresses during heat treatment of metals and alloys was developed. The model was integrated into the commercial FEA software MSC.Marc&reg / by user subroutines. The accuracy of the model was verified by simulating the quenching of eccentrically drilled steel cylinders. Simulation results were justified via SEM observations and XRD residual stress measurements. According to the results, the model can effectively predict the trends in the distribution of microstructure and residual stresses with a remarkable accuracy.

SNO+, the successor of the Sudbury Neutrino Observatory, is an upcoming low energy neutrino experiment, located in the 2 km deep laboratory SNOLAB, Canada. The spheric acrylic vessel in the detector center will contain 780 t of LAB. The main goal of SNO+ is the search for the neutrinoless double beta decay of 130Te, using a novel scintillator in which natural Te is bound with an initial loading of 0.3% via water and a surfactant. Within this thesis, the first measurement of the Alpha-particle and proton quenching parameters of loaded and unloaded LAB is described. These parameters are crucial for an efficient background suppression, necessary to reach a sensitivity above the current limit in 76Ge of T1/2(0v) > 2.1 x 10^(25) y (90% C.L.). For 0.3% Te-loading, the quenching parameter obtained is kB = (0.0070 +/- 0.0004) cm/MeV for Alpha-particles and kB = (0.0090 +/- 0.0003) cm/MeV for protons. Additionally, the spectral sensitivity of SNO+ to supernova electron anti-neutrinos and muon and tau (anti-)neutrinos is determined for the first time, using inverse beta decay and v-p elastic scattering with the measured quenching parameters. The obtained sensitivity to the mean energy of electron anti-neutrinos is E = 15.47^(+1.54)_(-2.43) MeV and of muon and tau (anti-)neutrinos is E = 17.81^(+3.49)_(-3.09) MeV. / SNO+, der Nachfolger des Sudbury Neutrino Observatorys, ist ein bevorstehendes Niederenergie-Neutrino-Experiment im 2 km tiefen Untergrundlabor SNOLAB in Kanada. Die Acryl-Kugel im Zentrum des Detektors wird mit 780 t LAB gefüllt werden. Das Hauptziel von SNO+ ist die Suche nach dem neutrinolosen Doppelbetazerfall von 130Te mit einem neuartigen Szintillator, in dem natürliches Te mit einer Anfangskonzentration von 0.3% über Wasser und ein Tensid gebunden wird. In dieser Arbeit wird erstmals die Messung der Alpha-Teilchen und Proton Quenching Parameter in diesem und in normalem LAB beschrieben. Die Parameter sind unverzichtbar für eine effiziente Untergrund Unterdrückung, die notwendig ist um auf das bestehende Limit in 76Ge von T1/2(0v) > 2.1 x 10^(25) y (90% C.L.) sensitiv zu sein. Der ermittelte Quenching Parameter bei 0.3% Te beträgt kB = (0.0070 +/- 0.0004) cm/MeV für Alpha-Teilchen und kB = (0.0090 +/- 0.0003) cm/MeV für Protonen. Zusätzlich wird erstmals die spektrale Sensitivität von SNO+ auf Supernova Elektron Anti-Neutrinos und Muon and Tau (Anti-)Neutrinos bestimmt über den inversen Betazerfall und die elastische v-p Streuung zusammen mit den gemessenen Quenching Parametern. Die ermittelte Sensitivität auf die mittlere Energie der Elektron Anti-Neutrinos ist E = 15.47^(+1.54)_(-2.43) MeV und der Muon und Tau (Anti-)Neutrinos ist E = 17.81^(+3.49)_(-3.09) MeV.

Thermal stimulation of geothermal wells is a production enhancement technique that is an attractive option to operators of geothermal fields as a way to enhance and revitalize well performance capabilities through injection of cold water into the geothermal reservoir. This thesis presents a review of thermal stimulation procedures that have been carried out at various geothermal fields worldwide, and then sets out to demonstrate through laboratory experiments the effects of thermal stimulation on typical reservoir rocks. Thermal damage to crustal rocks is important in many fields of practical engineering applications. Thermal fractures have been discussed in many studies, however their formation under fully water saturated conditions as a result of rapid quenching is not fully understood. In this study, a new methodology is designed to replicate thermal stimulation in such an environment, using an apparatus that allows rocks to be heated to 350°C at up to 22 MPa confining pressure and rapidly quenched with cold water to ambient temperature while maintaining system pressure. The results indicate that through thermal cycling in the apparatus, porosity was increased, density decreased, acoustic velocities attenuated and mechanical properties significantly altered. Maximum damage occurred during the first thermal cycle, a product of the thermo-mechanical Kaiser effect such that rocks should not experience additional damage unless a previous maximum stress is surpassed. The thesis details a comprehensive evaluation of the Rotokawa Andesite sourced from the Rotokawa Geothermal field located in the Taupo Volcanic Zone, New Zealand. The importance of microstructural fabrics on the physical properties of this reservoir lithology is demonstrated. The mineralogical and petrological fabrics of the rocks are coupled with detailed studies of the microstructural fracture networks, including measurements of porosity, density and permeability. Acoustic wave velocities and dynamic elastic moduli were determined. Uniaxial compressive strength testing coupled with acoustic emission have helped to determine the behavior of the rock under deformation and provided data to characterize the static elastic moduli of the rocks. These data are then utilized to build empirical, micromechanical and geometric relationships. To better constrain important engineering concerns such as wellbore stability, reservoir forecasting and stimulation procedures, thermal property measurements were carried out on samples recovered from the Rotokawa Andesite. In particular, measurements of linear thermal expansion, thermogravimetric analysis, and differential scanning calorimetry were measured utilizing varied experimental heating rates of 2, 5 and 20 K/min. The property analyses were carried out to determine if heating rates influenced the measurement of thermal properties, specifically thermal expansion coefficients and strain rate in the samples. Results indicate that thermal expansion is not heating rate dependent within the range investigated though the strain rate is significantly dependent on heating rate, with higher strain rates observed in conjunction with higher heating rates. By using a one dimensional stress model, a failure criterion can be established for the Rotokawa Andesite when subject to thermal stressing. The importance of this study is to further understand the critical heating and cooling rates at which thermal stress causes cracking within the Rotokawa reservoir. This can enhance permeability but can also affect wellbore stability, so constraining these conditions can be beneficial to resource utilization. To test effects of thermal stimulation in the laboratory, Rotokawa Andesite core was heated to 325ºC at pressure of 20 MPa and quenched rapidly to 20ºC while maintaining a pressure of 20 MPa. Permeability increased by an order of magnitude over original pre-treatment values. Ultrasonic velocities also reflected a significant change after stimulation testing. Scanning electron microscopy showed significant microstructural change to samples and supplemented physical property investigations. The results imply that thermal stimulation can be successfully repeated in the laboratory and is coupled with both thermal and chemical components. The results of these investigations are of profound importance for effective utilization and maintenance of the Rotokawa Geothermal field and the results also have implications for geothermal fields worldwide.

Because oxygen is vital to the metabolic processes of all eukaryotic cells, a detailed understanding of its transport and consumption is of great interest to researchers. Existing methods of quantifying oxygen delivery and consumption are non-ideal for in vivo measurements. They either lack the three-dimensional spatial resolution needed, are invasive and disturb the local physiology, or they rely on hemoglobin spectroscopy, which is not a direct measure of the oxygen available to cells. Consequently, many fundamental physiology research questions remain unanswered. This dissertation presents our development of a novel in vivo oxygen measurement technique that seeks to address the shortcomings of existing methods. Specifically, we have combined two-photon microscopy with phosphorescence quenching oximetry to produce a system that is capable of performing depth-resolved, high-resolution dissolved oxygen concentration (PO2) measurements. Furthermore, the new technique allows for simultaneous visualization of the micro-vasculature and measurement of blood velocity. We demonstrate the technique by quantifying PO2 in rodent cortical vasculature under normal and pathophysiologic conditions. We also demonstrate the technique’s usefulness in examining the changes in oxygen transport that result from acute focal ischemia in rodent animal models. / text