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Dans les milieux où la densité et la polarisation nucléaire sont importantes (par exemple l'eau dans un fort champ magnétique en RMN haute résolution, ou le xénon 129 et l'hélium 3 liquides polarisés au-delà de la polarisation d'équilibre par pompage optique), la densité d'aimantation est suffisante pour que la dynamique de cette aimantation soit influencée par les couplages non-linéaires induits par les champs magnétiques dipolaires. <br />Ce travail de thèse comprend d'abord une étude expérimentale des effets de ces couplages dipolaires dans un échantillon en forme de tube en U de xénon 129 liquide hyperpolarisé (jusqu'à 6% de polarisation obtenu par pompage optique) ; la dynamique de l'aimantation y est étudiée par résonance magnétique nucléaire (RMN) dans un champ magnétique peu intense (1.5 mT). <br />Puis nous détaillons quelques modèles numériques destinés à reproduire les comportements observés récemment dans les systèmes hyperpolarisés expérimentaux et plus généralement utilisables dans tous les cas où les couplages dipolaires jouent un rôle. <br /><br />Etude expérimentale et modélisations démontrent que les caractéristiques de l'évolution de l'aimantation dépendent crucialement de paramètres tels que la forme de l'échantillon, l'angle de basculement et l'importance relative des champs dipolaires et des variations spatiales des champs appliqués. Dans les échantillons anisotropes et à faibles angles de basculement, le spectre RMN présente une structure en plusieurs raies fines et résolues ("spectral clustering") ; ceci correspond à une organisation spatiale de l'aimantation en modes indépendants . <br />Dans tous les systèmes, à grands angles de basculement, les temps de vie peuvent être raccourcis de manière spectaculaire (de deux ordres de grandeur) ; ceci s'interprète comme une instabilité de précession aboutissant à des distributions désordonnées d'aimantation.

<p>Background:Pancreas cancer is a most aggressive malignancy. More than 80% of patients diagnosed with pancreas cancer, exhibit such advanced disease, that curative surgery is impossible. Systemic chemotherapy prolongs survival to 5-9 months. High concentrations of chemotherapeutic agents in the abdominal cavity and in the lymphatics draining the area is achieved by intraperitoneal administration. Vasopressin decreases splanchnic blood flow, reducing the intraperitoneal uptake of drugs, thus raising the local and lymphatic dose intensity.</p><p>Aim: The aim of the study was to investigate the feasibility and tumour response of intraperitoneal 5-Fluorouracil (5-FU) treatment in non-resectable pancreas cancer, using vasopressin to improve the pharmacokinetic profile. Further, to study the effect of vasopressin on peritoneal blood flow, altered by intraperitoneal 5-FU or the presence of peritoneal carcinomatosis.</p><p>Methods: In the animal experiments, the 133Xe-clearance technique and as a comparison Laser doppler flow, were used to identify changes of peritoneal blood flow caused by vasopressin in unmanipulated animals and in animals with peritoneal carcinomatosis or animals given intraperitoneal 5-FU. In the clinical studies, 68 (39 women/29 men) patients, with a non-resectable ductal pancreas cancer and a Karnovsky Index ≥70 were included. Patients were treated with 750-1500 mg/m2 5-FU intraperitoneally through a Port-a-cath and Leucovorin 100 mg/m2 intravenously on two consecutive days every 21 days until progression. Seventeen patients, receiving 750 mg/m2 5-FU, were given concomitant vasopressin 0.1 IU/min during 180 minutes, alternatively day 1 or 2.</p><p>Results: In the animal experiments, vasopressin 0.07 IU/kg/min significantly reduced the 133Xe-clearance. Intraperitoneal 5-FU decreased the basal peritoneal blood flow and abrogated the vasopressin effect for 1-2 days. The presence of peritoneal carcinomatosis did not influence the basal peritoneal blood flow, nor the reduction of peritoneal blood flow caused by vasopressin. In the clinical studies, the treatment with intraperitoneal 5-FU was well tolerated, with no WHO Grade 3 or 4 toxicity with doses up to 1250 mg/m2. Thirty patients achieved at least stable disease at three months. The median survival time was 8.0 (range 0.8-54.1) months. There was a significant reduction of 5-FU Cmax on day 2, but no significant reduction of AUC, when vasopressin was given.</p><p>Conclusion: Peritoneal blood flow changes caused by vasopressin can be estimated with the 133Xe-clearance technique. Intraperitoneal 5-FU but not peritoneal carcinomatosis decreases the vasopressin induced 133Xe-clearance reduction, 1-2 days after administration. In patients with non-resectable pancreas cancer, intraperitoneal 5-FU up to 1250 mg/m2 for two days every third week can be given without WHO grade 3 and 4 toxicity. The treatment is well tolerated with few and minor side effects. Tumour responses were observed. Addition of vasopressin does not significantly enhance the pharmacokinetics of intraperitoneal 5-Flurorouracil, but adds toxicity.</p>

Background:Pancreas cancer is a most aggressive malignancy. More than 80% of patients diagnosed with pancreas cancer, exhibit such advanced disease, that curative surgery is impossible. Systemic chemotherapy prolongs survival to 5-9 months. High concentrations of chemotherapeutic agents in the abdominal cavity and in the lymphatics draining the area is achieved by intraperitoneal administration. Vasopressin decreases splanchnic blood flow, reducing the intraperitoneal uptake of drugs, thus raising the local and lymphatic dose intensity. Aim: The aim of the study was to investigate the feasibility and tumour response of intraperitoneal 5-Fluorouracil (5-FU) treatment in non-resectable pancreas cancer, using vasopressin to improve the pharmacokinetic profile. Further, to study the effect of vasopressin on peritoneal blood flow, altered by intraperitoneal 5-FU or the presence of peritoneal carcinomatosis. Methods: In the animal experiments, the 133Xe-clearance technique and as a comparison Laser doppler flow, were used to identify changes of peritoneal blood flow caused by vasopressin in unmanipulated animals and in animals with peritoneal carcinomatosis or animals given intraperitoneal 5-FU. In the clinical studies, 68 (39 women/29 men) patients, with a non-resectable ductal pancreas cancer and a Karnovsky Index ≥70 were included. Patients were treated with 750-1500 mg/m2 5-FU intraperitoneally through a Port-a-cath and Leucovorin 100 mg/m2 intravenously on two consecutive days every 21 days until progression. Seventeen patients, receiving 750 mg/m2 5-FU, were given concomitant vasopressin 0.1 IU/min during 180 minutes, alternatively day 1 or 2. Results: In the animal experiments, vasopressin 0.07 IU/kg/min significantly reduced the 133Xe-clearance. Intraperitoneal 5-FU decreased the basal peritoneal blood flow and abrogated the vasopressin effect for 1-2 days. The presence of peritoneal carcinomatosis did not influence the basal peritoneal blood flow, nor the reduction of peritoneal blood flow caused by vasopressin. In the clinical studies, the treatment with intraperitoneal 5-FU was well tolerated, with no WHO Grade 3 or 4 toxicity with doses up to 1250 mg/m2. Thirty patients achieved at least stable disease at three months. The median survival time was 8.0 (range 0.8-54.1) months. There was a significant reduction of 5-FU Cmax on day 2, but no significant reduction of AUC, when vasopressin was given. Conclusion: Peritoneal blood flow changes caused by vasopressin can be estimated with the 133Xe-clearance technique. Intraperitoneal 5-FU but not peritoneal carcinomatosis decreases the vasopressin induced 133Xe-clearance reduction, 1-2 days after administration. In patients with non-resectable pancreas cancer, intraperitoneal 5-FU up to 1250 mg/m2 for two days every third week can be given without WHO grade 3 and 4 toxicity. The treatment is well tolerated with few and minor side effects. Tumour responses were observed. Addition of vasopressin does not significantly enhance the pharmacokinetics of intraperitoneal 5-Flurorouracil, but adds toxicity.

The ionization of xenon Rydberg atoms at metallic surfaces is examined. The data show that, when the effects of stray electric "patch" fields present on the surface are taken into account, ionization is well described by a simple over-the-barrier model. The patch fields are determined from direct measurements of the potential variations across the target surfaces using Kelvin probe force microscopy. Monte Carlo techniques are used to model the atom-surface interaction. The results confirm the important role that patch fields can play during Rydberg atom-surface interactions and suggest that such interactions can provide a sensitive probe of stray fields at surfaces. To demonstrate this, measurements of the threshold conditions required to observe ions resulting from surface ionization are used to estimate how large such stray fields can be. The data show that the stray fields can be sizable, as large as ∼ 10 3 V · cm -1 100 nm from the surface and ∼ 10 V · cm -1 500 nm from the surface, and illustrate the potential of Rydberg atoms for detecting and characterizing surface electric fields. Methods to enhance the surface ionization signal using electrode arrays patterned on a surface are investigated. Simulations show that bias voltages applied to a series of parallel wires comprised of two interleaved comb-shaped electrodes can have a dramatic impact on ion collection efficiency. It is suggested that such a surface can be used to efficiently collect low- n Rydberg atoms ( n [Special characters omitted.] 10). Significant progress towards fabrication of a functioning surface of 1 μm wide wires with 1 μm spacing is documented.

The research presented in this thesis makes use of theoretical/computational techniques to calculate nonlinear spectroscopic signals and molecular volumes. These techniques have become more practical with advances in computational resources and now are an integral part of research in these areas. Preliminary results allude to the power of these techniques when applied to relevant problems and suggest that much progress can be made in understanding the complex nature of nonlinear spectroscopic signals and molecular volume contributions. The nonlinear spectroscopy work involves writing the quantum mechanical response functions in terms of classical time correlation functions which are amenable to calculation using classical molecular dynamics. The response functions reported in this thesis include the fifth order response function, probed in the fifth order Raman experiment, and the third order response function probed in the two dimensional infrared experiment. The molecular volume calculations make use of modern algorithms used in molecular dynamics simulations to calculate the full thermodynamic volumes of molecules.

The volatile inventories of the Earth and Moon reflect unique histories of volatile acquisition and loss in the early Solar System. The terrestrial volatile inventory was established after the giant impact phase of accretion, and the planet subsequently settled into a regime of long-term volatile exchange between the mantle and surface reservoirs in association with plate tectonics. Therefore, volatiles in the Earth and Moon shed light on a diverse array of processes that shaped planetary bodies in the Solar System as they evolved to their present-day states. / Earth and Planetary Sciences

Structural biology is a branch of science related to biochemistry, biophysics, and molecular biology that deals with the molecular structures of biological macromolecules, in particular nucleic acids and proteins. Structure-guided drug design uses three-dimensional knowledge of protein structures to design small molecules which block the action of specific proteins. When crystals of theses macromolecules and their complexes can be obtained, their crystal structures can be determined by using isomorphous differences between a native structure and a derivative structure. This allows crystallographers to determine the coordinates of a small number of heavy atoms which provide initial phases for macromolecules. The advent of synchrotron radiation allowed determination of a heavy atom substructure by use of anomalous differences using either multiple wavelengths (MAD) or a single wavelength (SAD); the latter has become the most common phasing method in crystallography and is the method used in this study. The use of SeMet has been by far the most successful method employed in SAD. However, in some cases production of SeMet proteins is not possible thus necessitating additional options, for example, xenon. Noble gases such as xenon may be used in SAD experiments by binding to various, non-specific sites. Advances in noble gas pressurization systems like the Hampton Research Xenon Chamber have greatly eased the production of noble gas derivatives, xenon itself being a prime candidate with a very strong anomalous signal when compared to lighter noble gases like krypton and argon. Investigation of the phasing properties of xenon was carried out on test proteins hen egg white lysozyme (HEWL), thermolysin, glucose isomerase, and thaumatin II. Phases were successfully determined for all four proteins including thaumatin II which did not bind xenon but was successful due to the anomalous signal from 17 native sulfurs. The three remaining proteins showed varying occupancies and numbers of sites including xenon sites in thermolysin and glucose isomerase which have not been observed previously. This document will serve as a guide for the preparation of xenon derivative crystals and provides a strategy for the collection and processing of data from xenon derivatives.

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