<p dir="ltr">The objective of this research is to advance the development and application of laser diagnostics in gas phase medium, which ranges from atmospheric non-reacting flows to turbulent reacting flows in high-pressure, high-temperature environments. Laser diagnostic techniques are powerful tools for non-intrusive and in-situ measurements of important chemical parameters, such as temperature, pressure, and species mole fractions, in harsh environments. These measurements significantly advance the knowledge across various research disciplines, such as combustion dynamics, chemical kinetics, and molecular spectroscopy. In this thesis, detailed theoretical models and experimental analysis are presented for three different techniques: 1. Chirped-probe-pulse femtosecond coherent anti-Stokes Raman scattering (CPP fs CARS); 2. Two-color polarization spectroscopy (TCPS); 3. Ultrafast-laser-absorption-spectroscopy (ULAS). The first chapter provides a brief survey of laser diagnostics, including both linear and nonlinear methods. The motivations behind the three studies covered in this dissertation are also discussed. </p><p dir="ltr">In the second chapter, single-shot CPP fs CARS thermometry is developed for the hydrogen molecule at 5 kHz. The results are divided into two parts. The first part concentrates on the development of H₂ CPP fs CARS thermometry for high-pressure and high-temperature conditions. The second part demonstrates the application of H₂ CPP fs CARS in a model rocket combustor at pressures up to 70 bar. In the first part, H₂ fs CARS thermometry was performed in Hencken burner flames up to 2300 K, as well as in a heated gas-cell at temperatures up to 1000 K. It was observed that the H₂ fs CARS spectra are highly sensitive to the pump and Stokes chirp. Chirp typically originates from optical components such as windows and polarizers. As a result, the pump delay is modeled to provide a shift to the Raman excitation efficiency curve. With the updated theoretical model, excellent agreement was found between the simulated and experimental spectra. The averaged error and precision are 2.8% and 2.3%, respectively. In addition, the spectral phase and pump delay determined from the experimental spectra closely align with the theoretical predictions. It is also found that pressure does not have significant effects on the H₂ fs CARS spectra up to 50 bar at 1000 K. The collision model provides excellent agreement with the experiment. This allows the use of low-pressure laser parameters for high-pressure thermometry measurements. In the second part, spatially resolved H₂ temperature was measured in a rocket chamber at pressures up to 70 bar. This is the first demonstration of fs CARS thermometry inside a high-pressure rocket combustor. These results highlight the potential of using H₂ CPP fs CARS thermometry to provide quantitative data in high-pressure experiments for the study of combustion dynamics and model validation efforts at application relevant operating conditions.</p><p dir="ltr">The third chapter presents the development of a TCPS system for the study of the NO (<i>A</i>²Σ⁺-<i>X</i>²Π) state-to-state collision dynamics with He, Ar, and N₂. Two sets of TCPS spectra for 1% NO, diluted in different buffer gases at 295 K and 1 atm, were obtained with the pump beam tuned to the R₁₁(11.5) and ^OP₁₂(1.5) transitions. The probe was scanned while the pump beam was tuned to the line center. Collision induced transitions were observed in the spectra as the probe scanned over transitions that were not coupled with the pump frequency. The strength and structure of the collision induced transitions in the TCPS spectra were compared between the three colliding partners. Theoretical TCPS spectra, calculated by solving the density matrix formulation of the time-dependent Schrödinger wave equation, were compared with the experimental spectra. A collision model based on the modified exponential-gap law was used to model the rotational level-to-rotational level collision dynamics. An unique aspect of this work is that the collisional transfer from an initial to a final Zeeman state was modeled based on the difference in the cosine of the rotational quantum number <i>J</i> projection angle with the z-axis for the two Zeeman states. Rotational energy transfer rates and Zeeman state collisional dynamics were varied to obtain good agreement between theory and experiment for the two different TCPS pump transitions and for the three different buffer gases. One key finding, in agreement with quasi-classical trajectory calculations, is that the spin-rotation changing transition rate in the <i>A</i>²Σ⁺ level of NO is almost zero for rotational quantum numbers ≥ 8. It was necessary to set this rate to near zero to obtain agreement with the TCPS spectra. </p><p dir="ltr">The fourth chapter presents the development and application of a broadband ULAS technique operating in the mid-infrared for simultaneous measurements of temperature, methane (CH₄), and propane (C₃H₈) mole fractions. Single-shot measurements targeting the C-H stretch fundamental vibration bands of CH₄ and C₃H₈ near 3.3 μm were acquired in both a heated gas cell up to ~650 K and laminar diffusion flames at 5 kHz. The average temperature error is 0.6%. The average species mole fraction error are 5.4% for CH₄, and 9.9% for C₃H₈. This demonstrates that ULAS is capable of providing high-fidelity hydrocarbon-based thermometry and simultaneous measurements of both large and small hydrocarbons in combustion gases. </p>

Im Folgenden werden Transferprozesse in Nanohybridsystemen theoretisch untersucht. Diese Hybridsysteme sind vielversprechende Kandidaten für neue optoelektronische Anwendungen und erfahren daher ein erhebliches Forschungsinteresse. Jedoch beschränken sich Arbeiten darüber hauptsächlich auf experimentelle Untersuchungen und kaum auf die dazugehörige theoretische Beschreibung. Bei den theoretischen Betrachtungen treten entscheidende Limitierungen auf. Es werden entweder Details auf der atomaren Ebene vernachlässigt oder Systemgrößen betrachtet, die wesentlich kleiner als im Experiment sind. Diese Thesis zeigt, wie die bestehenden Theorien verbessert werden können und erweitert die bisherigen Untersuchungen durch die Betrachtung von vier neuen hoch relevanten Nanohybridsystemen. Das erste System ist eine Nanostruktur, die aus einem Au-Kern und einer CdS-Schale besteht. Beim zweiten System wurde eine ZnO/Para-Sexiphenyl Nanogrenzfläche untersucht. Die zwei anderen Systeme beinhalten jeweils einen CdSe-Nanokristall, der entweder mit einem Pheophorbide-a-Molekül oder mit einem röhrenförmigen Farbstoffaggregat wechselwirkt. In allen Systemen ist der Anregungsenergie-Transfer ein entscheidender Transfermechanismus und steht im Fokus dieser Arbeit. Die betrachteten Hybridsysteme bestehen aus zehntausenden Atomen und machen daher eine individuelle Berechnung der einzelnen Subsysteme sowie deren gegenseitiger Wechselwirkung notwendig. Die Halbleiter-Nanostrukturen werden mit der Tight-Binding-Methode und der Methode der Konfigurationswechselwirkung beschrieben. Für das molekulare System wird die Dichtefunktionaltheorie verwendet. Die dazugehörigen Rechnungen wurden von T. Plehn ausgeführt. Das metallische Nanoteilchen wird durch quantisierte Plasmon-Moden beschrieben. Die verwendeten Theorien ermöglichen eine Berechnung von Anregungsenergietransfer in Nanohybridsystemen von bisher nicht gekannter Systemgröße und Detailgrad. / In the following, transfer phenomena in nanohybrid systems are investigated theoretically. Such hybrid systems are promising candidates for novel optoelectronic devices and have attracted considerable interest. Despite a vast amount of experimental studies, only a small number of theoretical investigations exist so far. Furthermore, most of the theoretical work shows substantial limitations by either neglecting the atomistic details of the structure or drastically reducing the system size far below the typical device extension. The present thesis shows how existing theories can be improved. This thesis also expands previous theoretical investigations by developing models for four new and highly relevant nanohybrid systems. The first system is a spherical nanostructure consisting of an Au core and a CdS shell. By contrast, the second system resembles a finite nanointerface built up by a ZnO nanocrystal and a para-sexiphenyl aggregate. For the last two systems, a CdSe nanocrystal couples either to a pheophorbide-a molecule or to a tubular dye aggregate. In all of these systems, excitation energy transfer is an essential transfer mechanism and is, therefore, in the focus of this work. The considered hybrid systems consist of tens of thousands of atoms and, consequently, require an individual modeling of the constituents and their mutual coupling. For each material class, suitable methods are applied. The modeling of semiconductor nanocrystals is done by the tight-binding method, combined with a configuration interaction scheme. For the simulation of the molecular systems, the density functional theory is applied. T. Plehn performed the corresponding calculations. For the metal nanoparticle, a model based on quantized plasmon modes is utilized. As a consequence of these theories, excitation energy transfer calculations in hybrid systems are possible with unprecedented system size and complexity.

Hybride anorganisch/organischen Systeme können die individuellen Vorteile, etwa eine hohe elektronische Mobilität in anorganischen und starke Licht-Materie-Wechselwirkung in organischen Halbleitern, kombinieren. Ein sinnvoller Nutzen dieser Heterostrukturen benötigt ein umfassendes Verständnis der Grenzfläche. Zwei Grenzflächenprozesse werden in dieser Arbeit behandelt. Förster-Resonanzenergietransfer (FRET) wird zwischen einem InGaN/GaN Quantengraben und dem Polymer Cn-ether PPV untersucht. Trotz des hohen internen elektrischen Feldes im Quantengraben, ist effizienter Energietransfer möglich, solange andere nicht-strahlende Zerfallsprozesse unterdrückt werden. Dies wird mittels temperaturabhängiger PL und PLE Spektroskopie gezeigt. PLE demonstriert eine eindeutige Erhöhung der Emission des Akzeptors. Bei höheren Temperaturen dominieren nicht-strahlende Zerfallskanäle. Ladungstransfer wird zwischen MoS2 und dem Molekül H2Pc untersucht. Die Kombination mit organischen Molekülen kann die Funktionalität von MoS2 erweitern. Photoelektronenspektroskopie (PES) zeigt einen Typ-II Heteroübergang an der MoS2/H2Pc Grenzfläche. Angeregte Elektronen gehen von den H2Pc Molekülen in die MoS2 Monolage über, wie mittels einer Verkürzung der PL Lebenszeit von H2Pc gezeigt wird. Photostrommessungen demonstrieren zudem, dass die transferierten Elektronen zu einer erhöhten Photoleitfähigkeit beitragen. Zusätzlich werden auch einzelne 2D Übergangsmetall Dichalkogenide (TMDCs) untersucht. Um TMDCs von hoher Qualität herzustellen, wurde intern eine Wachstumsmethode entwickelt. Mittels PL Spektroskopie werden die so hergestellten Schichten charakterisiert. Die Vielseitigkeit der Methode wird anhand des Wachstums von Mischkristallen und Heterostrukturen gezeigt. Der Einfluss der dielektrischen Funktion des Substrates wird erforscht. Durch die Kombination von PES und Reflexionsmessungen kann eine gleichzeitige Abnahme sowohl der Bandlücke als auch der Exzitonen Bindungsenergie gezeigt werden. / Hybrid inorganic/organic systems can combine the advantages of both materials such as high carrier mobilities in inorganic semiconductors and large light-matter interaction in organic ones. In order to benefit from these heterostructures, a thorough understanding of the interface is needed. Two processes occurring at the interface are looked at in this thesis. Förster resonance energy transfer (FRET) is studied between a single InGaN/GaN quantum well and the polymer Cn-ether PPV. Despite the large internal electric fields in the quantum well, efficient FRET is possible as long as other non-radiative decay channels are suppressed. This is shown by temperature dependent PL and PLE spectroscopy. PLE spectra clearly demonstrate an enhanced light emission from the acceptor. At elevated temperatures, non-radiative decay pathways become dominant. Excited-state charge transfer is studied on MoS2 in combination with the molecule H2Pc. The combination with molecules can extend the functionality of MoS2. Photoelectron spectroscopy (PES) reveals a type II energy level alignment at the MoS2/H2Pc interface. Excited electrons are transferred from H2Pc to MoS2, deduced from a shortening of the H2Pc PL decay time. Photocurrent spectra further show that the transferred electrons contribute to an enhanced photoconductivity. Additionally, bare 2D transition-metal dichalcogenides (TMDCs) are studied. In order to fabricate high-quality TMDC monolayers, a growth method was developed in-house. The grown monolayers are characterised by optical spectroscopy. The versatility of the method is demonstrated by the growth of alloys and heterostructures. The influence of the substrate dielectric function is investigated by comparing band-gaps measured by PES with the exciton transition energies obtained by reflectance measurements. An almost equal reduction in both energies with the substrate dielectric constant is seen.

Aufkonvertierende (upconverting; UC) Nanomaterialien bilden eine neue Klasse nichtlinearer lumineszenter Reporter, die nah-infrarotes (NIR) Anregungslicht in Photonen von höherer Energie umwandeln. Das effizienteste bekannte UC-System bildet hierbei β-NaYF4: 20%Yb(III), 2%Er(III) mikrokristallines Bulkmaterial, für welches UC-Quantenausbeuten (ΦUC) von 10 % berichtet werden, während ΦUC von Nanokristallen (nanocrystals; NC) um mehrere Größenordnungen niedriger sein können. Um die Effizienz von UC-Nanomaterialien zu erhöhen, werden NC üblicherweise mit inerten Schalen versehen. In dieser Arbeit werden mehrere verschiedene Bulkmaterialien spektroskopisch untersucht, um ein Vergleichsmaterial auszuwählen, das als Maßstab für alle folgenden, vergleichbaren Messungen an NC dient. Die Oberfläche von ultrakleinen (3.7±0.5) nm NC wird mit Schalen von bis zu 10 nm Dicke versehen, um die optimale Schalendicke für vollständige Oberflächenpassivierung zu identifizieren, allerdings weisen die Ergebnisse auf eine mögliche Kern-Schale-Durchmischung hin. In einer zweiten Studie werden die unterschiedlichen Dotanden, Er(III) und Yb(III), auf ihre optischen Eigenschaften sowie die Einflüsse von Energietransfer (ET) und von ihrer Umgebung spektroskopisch untersucht. Dabei kann klar zwischen Oberflächeneffekten und oberflächenunabhängigen Volumeneffekten unterschieden werden. Die Ergebnisse werden durch ein einfaches Monte-Carlo-Modell gestützt, durch das die größen- und leistungsdichte-(P-)abhängigen Populierungsdynamiken der strahlenden Banden von Er(III) vorhergesagt werden können. Zuletzt werden durch eine verbesserte Synthesemethode UCNC mit stark verbesserten Lumineszenzeigenschaften hergestellt, mit denen bei vergleichsweise niedrigen P die gleichen ΦUC wie beim Bulkmaterial erreicht werden. Dies liefert einen Einblick in vielfältige Anwendungsmöglichkeiten für UCNC. / Upconversion (UC) nanomaterials are an emerging new class of non-linear luminescent reporters which convert near-infrared (NIR) excitation light into higher-energy photons. The most efficient known UC material is the β-NaYF4: 20%Yb(III), 2%Er(III) bulk (microcrystalline) phosphor with reported UC quantum yields (ΦUC) of 10 %, while ΦUC of nanocrystals (NC) can be several orders of magnitude lower. Strategies to improve the efficiency of UC nanomaterials include surface passivation with inert shells. In this work, several different bulk materials are compared to select one benchmark material for comparisons with NC analyzed with the same measurement techniques. The surface of ultrasmall (3.7 ± 0.5) nm NC is coated with inert shells of up to 10 nm thickness to identify an optimal shell thickness for complete surface passivation, but the results suggest core-shell intermixing. To distinguish between the different dopant ions, Er(III) and Yb(III), and the effect of energy transfer (ET) in a second study, single- and co-doped UCNC are investigated spectroscopically and the influence of their environment is determined thoroughly. Herein, a clear distinction between surface-related and surface-independent, volume-related effects is achieved and the results are emphasized by the use of a simple random walk model which accurately predicts size- and power density (P)-dependent population dynamics of the emissive bands of Er(III). Finally, utilizing an improved synthesis technique, UCNC with enhanced luminescence properties are produced, reaching the same ΦUC as the benchmarked bulk material at reasonably low P, providing an insight into numerous possible applications of UCNC.

No description available.

<p>One of the fundamental predictions of quantum mechanics is the occurrence of random fluctuations which can induce a measurable force between neutral objects, known as the Casimir effect. Casimir effect has attracted a lot of interest in both theoretical and practical work since the first prediction in 1948 because it is the most accessible evidence of quantum electromagnetic fluctuations in vacuum. Besides, it has prospective applications for nanotechnology and for studying fundamental physical theories beyond the standard model. In this dissertation, we report the experimental and theoretical progress towards realizing Casimir-based devices and long sought-after vacuum friction. </p> <p><br></p> <p>First, we propose and experimentally realize the first Casimir diode system that can regulate energy transfer along one direction through quantum vacuum fluctuations. This is the first experimental demonstration of non-reciprocal energy transfer by Casimir effects. We develop a dual-cantilever vacuum system which can be used to measure the Casimir force at separations from 50 nm to 1000 nm.  Parametric coupling scheme is applied to the system to couple two cantilevers with different resonant frequencies by Casimir interaction. By controlling the system near the exceptional point, we are able to break the time reversal symmetry and observe the non-reciprocal energy transfer. </p> <p><br></p> <p>The description of the Casimir diode system is followed by an experimental demonstration of the Casimir transistor system where we achieve the first measurement of Casimir interaction between three macroscopic objects. Three cantilevers can be coupled through quantum vacuum fluctuations by the parametric coupling scheme. Moreover, we have realized the first three-terminal Casimir transistor system that can switch and amplify quantum vacuum mediated energy transfer. These two Casimir-based devices will have potential applications in sensing and information processing.  </p> <p><br></p> <p>Subsequently, the first observation of Casimir mediated non-contact friction is demonstrated experimentally. When two parallel surfaces are moving with a relative velocity, they will experience quantum vacuum friction force which tries to slow down the relative motion because of quantum vacuum fluctuations. The quantum vacuum friction comes from the exchange of virtual photons between two moving bodies.  We have designed a novel method to detect the Casimir force mediated non-contact friction force between two harmonic oscillators. The non-contact friction comes from the interaction of virtual photons and phonons. We have experimentally detected the effect of non-contact friction and successfully measured the friction force at different velocities. </p> <p><br></p> <p>In the latter part of this thesis, two theoretical proposals about detecting the Casimir torque and rotational quantum vacuum friction torque by a levitated optomechanical system are discussed. The optically levitated nanoparticle system is a good candidate for precision measurements because it can achieve an ultrahigh mechanical quality factor due to the well isolation from the thermal environment. The calculation of the Casimir torque on a levitated nanorod near a birefringent plate is demonstrated. The calculation of the rotational quantum vacuum friction torque on a rotating nanosphere near a plate is also presented. By comparing these small torques to the sensitivity of our levitation system, we show that it is feasible to detect the Casimir torque and the rotational quantum vacuum friction torque under realistic conditions in the near future. </p> <p><br></p>

Monte-Carlo calculations are used to simulate the stochastic effects of fast neutron-induced chemical changes in the radiolysis of the ferrous sulfate (Fricke) dosimeter. To study the dependence of the yield of ferric ions, G(Fe[superscript 3+]), on fast neutron energy, we have simulated, at 25 [degree centigrade], the oxidation of ferrous ions in aerated aqueous 0.4 M H[subscript 2]SO[subscript 4] (pH 0.46) solutions when subjected to ~0.5-10 MeV incident neutrons, as a function of time up to ~50 s. The radiation effects due to fast neutrons are estimated on the basis of track segment (or"escape") yields calculated for the first four recoil protons with appropriate weighting according to the energy deposited by each of these protons. For example, a 0.8-MeV neutron generates recoil protons of 0.505, 0.186, 0.069, and 0.025 MeV, with linear energy transfer (LET) values of ~41, 69, 82, and 62 keV/[micro]m, respectively. In doing so, we consider that further recoils make only a negligible contribution to radiation processes. Our results show that the radiolysis of dilute aqueous solutions by fast neutrons produces smaller radical yields and larger molecular yields (relative to the corresponding yields for the radiolysis of water by [superscript 60]Co [gamma]-rays or fast electrons) due to the high LET associated to fast neutrons. The effect of recoil ions of oxygen, which is also taken into account in the calculations, is shown to decrease G(Fe[superscript 3+]) by about 10%. Our calculated values of G(Fe[superscript 3+]) are found to increase slightly with increasing neutron energy over the energy range covered in this study, in good agreement with available experimental data. We have also simulated the effect of temperature on the G(Fe[superscript 3+]) values in the fast neutron radiolysis of the Fricke dosimeter from 25 to 300 [degree centigrade]. Our results show an increase of G(Fe[superscript 3+]) with increasing temperature, which is readily explained by an increase in the yields of free radicals and a decrease in those of molecular products. For 0.8-MeV incident neutrons (the only case for which experimental data are available in the literature), there is a ~23% increase in G(Fe[superscript 3+]) on going from 25 to 300 [degree centigrade]. Although these results are in reasonable agreement with experiment, more experimental data, in particular for different incident neutron energies, would be needed to test more rigorously our Fe[superscript 3+] ion yield results at elevated temperatures.

Résumé : Le contrôle de la chimie de l'eau dans un réacteur nucléaire refroidi à l'eau nécessite une compréhension détaillée des effets de la radiolysede l'eau afin de limiter la corrosion et la dégradation des matériaux par oxydation générée par les produits de cette radiolyse. Toutefois, la mesure directe de la chimie dans le cœur des réacteurs est extrêmement difficile, sinon impossible, en raison des conditions extrêmes de haute température et haute pression, et les champs d’irradiation mixtes neutrons/γ, qui ne sont pas compatibles avec l'instrumentation chimique normale. Pour ces raisons,des modèles théoriques et des simulations sur ordinateur sont essentielles pour la prédiction de la chimie sous rayonnement de l'eau de refroidissement dans le cœur et son impact sur les matériaux. Dans ce travail, des simulations Monte Carlo ont été utilisées pour calculer les rendements des principales espèces (e[indice supérieur -][indice inférieur aq], H[indice supérieur •], H[indice inférieur 2], [indice supérieur •]OH et H[indice inférieur 2]O[indice inférieur 2]) formées lors de la radiolyse de l’eau liquide neutre par des neutrons mono-énergétiques de 2 MeV à des températures entre 25 et 350 °C. Le choix des neutrons de 2 MeV comme énergie d'intérêt est représentatif du flux de neutrons rapides dans un réacteur. Pour l'eau légère, la contribution la plus significative à la radiolyse vient des quatre premières collisions des neutrons qui produisent, dans la majorité des cas, des protons avec des énergies de recul de ~1.264, 0.465, 0.171 et 0.063 MeV et des transferts d’énergie linéique (TEL) moyens respectivement de ~22, 43, 69et 76 keV/[micro]m. Par ailleurs, nous avons négligé les effets des radiations dus aux ions de recul de l’oxygène. Les rendements moyens finaux peuvent alors être estimés comme étant la somme des rendements résultant de l’action de ces protons après pondérations en fonction de l’énergie déposée. Les rendements ont été calculés à 10[indice supérieur -7], 10[indice supérieur -6] et 10[indice supérieur -5] s. Les valeurs obtenues sont en accord avec les données expérimentales disponibles. En comparant nos résultats avec les données obtenues pour les rayonnements à faible TEL (rayons γ de [indice supérieur 60]Co ou électrons rapides), nos rendements calculés pour les neutrons rapides ont montré une dépendance en température essentiellement similaire, mais avec des valeurs plus faibles pour les rendements en radicaux libres et des valeurs plus élevées pour les rendements moléculaires. Nous avons également utilisé les simulations Monte Carlo pour étudier l'existence de la chute rapide de la constante de vitesse de réaction de l'électron hydraté (e[indice supérieur -][indice inférieur aq]) sur lui-même – l’une des principales sources de formation de H[indice inférieur 2] – au-dessus de 150 °C. Cette dépendance en température a été observée expérimentalement en milieu alcalin par divers auteurs, mais jamais en milieu neutre. Lorsque cette baisse de la constante de vitesse d’auto-réaction de e[indice supérieur -][indice inférieur aq] est incluse dans nos codes de simulation, tant pour des rayonnements de bas TEL (grappes isolés) que de haut TEL (trajectoires cylindriques), g(H[indice inférieur 2]) montre une discontinuité marquée à la baisse à ~150°C, ce qui n'est pas observée expérimentalement. Les conséquences de la présence de cette discontinuité dans le rendement en H[indice inférieur 2] pour les rayonnements à bas et haut TEL sont discutées. Enfin, nous avons tenté d’expliquer l'augmentation – considérée comme anormale – du rendement en H[indice inférieur 2] en fonction de la température au-dessus de 200 °C par l’intervention de la réaction des atomes H[indice supérieur •] avec l'eau, préalablement proposée par Swiatła-Wojcik et Buxton en 2005. La constante de vitesse de cette réaction est toujours controversée. // Abstract : Controlling the water chemistry in a water-cooled nuclear power reactor requires understanding and mitigating the effects of water radiolysis to limit the corrosion and degradation of materials by oxidizing radiolysis products. However, direct measurement of the chemistry in reactor cores is extremely difficult due to the extreme conditions of high temperature, pressure, and mixed neutron/γ-radiation fields, which are not compatible with normal chemical instrumentation. For these reasons, theoretical models and computer simulations are essential for predicting the detailed radiation chemistry of the cooling water in the core and the impact on materials. Monte Carlo simulations were used to calculate the yields for the primary species (e[superscript -][subscript aq], H[superscript •], H[subscript 2], [superscript •]OH, and H[subscript 2]O[subscript 2]) formed from the radiolysis of neutral liquid water by mono-energetic 2-MeV neutrons and the mechanisms involved at temperatures between 25 and 350 °C. In this work, we chose 2-MeV neutron as our energy of interest since it is known as representative of a fast neutron flux in a nuclear reactor. For light water, for that chosen energy, the most significant contribution to the radiolysis comes from the first four neutron collisions that generate mostly ejected protons with energies of ~1.264, 0.465, 0.171, and 0.063 MeV, which had, at 25 °C, mean linear energy transfers (LETs) of ~22, 43, 69, and 76 keV/[micro]m, respectively. In this work, we simply neglected the radiation effects due to oxygen ion recoils. The average final fast neutron yields could be estimated as the sum of the yields for these protons after allowance was made for the appropriate weightings (by using the Eq (2) in Chapter 4) according to their deposited energy. Yields were calculated at 10[superscript -7], 10[superscript -6] and 10[superscript -5] s. Our computed yield agreed reasonably well with the available experimental data. By comparing our results with data obtained for low-LET radiation ([superscript 60]Co γ-rays or fast electrons), our computed yields for fast neutron radiation showed essentially similar temperature dependences over the range of temperature studied, but with lower values for yields of free radicals and higher values for molecular yields. In this work, we also used our Monte Carlo simulation to investigate the existence of drop of hydrated electron (e[superscript -][subscript aq]) self-reaction rate constant at 150 °C. One of the main sources of H[subscript 2] formation is the self-reaction of hydrated electrons. The temperature dependence of the rate constant of this reaction (k[subscript 1]), measured under alkaline conditions, reveals that the rate constant drops abruptly above ~150 °C. However, when this drop in the e[superscript -][subscript aq] self-reaction rate constant is included in our code for low (isolated spurs) and high (cylindrical tracks) linear energy transfer (LET), g(H[subscript 2]) shows a marked downward discontinuity at ~150 °C which is not observed experimentally. The consequences of the presence of this discontinuity in H[subscript 2] yield for both low and high LET radiation are discussed. Another reaction that might explain the anomalous increasing of H[subscript 2] yield with temperature is the reaction of H[superscript •] atoms with water previously proposed by Swiatla-Wojcik and Buxton (2005) whose rate constant is still in controversial.

Membrane protein dynamics is of great importance for living organisms. The precise localization of proteins composing a synapse on the membrane facing a nerve terminus is essential for proper functioning of the nervous system. In muscle fibers, the nicotinic acetylcholine is densely packed under the motor nerve termini. A receptor associated protein, rapsyn, acts as a linker between the receptor and the other components of the synaptic suramolecular assembly. Advances in fluorescence microscopy have allowed to measure the behavior of a single receptor in the cell membrane. In this work single-molecule microscopy was used to track the motion of ionotropic acetylcholine (nAChR) and serotonin (5HT3R) receptors in the plasma membrane of cells. We present methods for measuring single-molecule diffusion and their analysis. Single molecule tracking has shown a high dependence of acetylcholine receptors diffusion on its associated protein rapsyn. Comparing muscle cells that either express rapsyn or are devoid of it, we found that rapsyn plays an important role on receptor immobilization. A three-fold increase of receptor mobility was observed in muscle cells devoid of rapsyn. However, in these cells, a certain fraction of immobilized receptors was also found immobile. Furthermore, nAChR were strongly confined in membrane domains of few tens of nanometers. This showed that membrane composition and membrane associated proteins influence on receptor localization. During muscle cell differentiation, the fraction of immobile nAChR diminished along with the decreasing nAChR and stable rapsyn expression levels. The importance of rapsyn in nAChR immobilization has been further confirmed by measurements in HEK 293 cells, where co-expression of rapsyn increased immobilization of the receptor. nAChR is a ligand-gated ion-channel of the Cys-loop family. In mammals, members of this receptor family share general structural and functional features. They are homo- or hetero-pentamers and form a membrane-spanning ion channel. Subunits have three major regions, an extracellular ligand binding domain, a transmembrane channel and a large intracellular loop. 5HT3R was used as a model to study the effect of this loop on receptor mobility. Single-molecule tracking experiments on receptors with progressively larger deletions in the intracellular loop did not show a dependence of the size of the loop on the diffusion coefficient of mobile receptors. However, two regions were identified to play a role in receptor mobility by changing the fractions of immobile and directed receptors. Interestingly, a prokaryotic homologue of cys-loop receptors, ELIC, devoid of a large cytoplasmic loop was found to be immobile or to show directed diffusion similar as the wild-type 5HT3R. The scaffolding protein rapsyn stabilizes nAChR clusters in a concentration dependent manner. We have measured the density and self-interactions of rapsyn using FRET microscopy. Point-mutations of rapsyn, known to provoke myopathies, destabilized rapsyn self-interactions. Rapsyn-N88K, and R91L were found at high concentration in the cytoplasm suggesting that this modification disturbs membrane association of rapsyn. A25V was found to accumulate in the endoplasmic reticulum. Fluorescent tools to measure intracellular concentration of calcium ions are of great value to study the function of neurons. Rapsyn is highly abundant at the neuromuscular junction and thus is a genuine synaptic marker. A fusion protein of rapsyn with a genetically encoded ratiometric calcium sensor has been made to probe synapse activity. This thesis has shown that the combined use of biologically relevant system and modern fluorescence microscopy techniques deliver important information on pLGIC behaviour in the cell membrane. / <p>QC 20151217</p>

Les récepteurs couplés aux protéines G (RCPG) constituent la plus grande famille de protéines membranaires du génome humain. Ils transmettent les signaux extracellulaires provenant de plusieurs stimuli comme les odeurs, les ions, les hormones et les neurotransmetteurs, à l'intérieur des cellules. En se liant aux RCPGs, ces molécules contribuent à la stabilisation des changements conformationnels activateurs qui se propagent jusqu'au domaine intracellulaire des récepteurs. Ces derniers engagent ensuite un ou plusieurs effecteurs, comme les protéines G hétérotrimériques et les β-arrestines (βarrs), qui activent une cascade d'événements moléculaires menant à la réponse cellulaire.Récemment, la publication de structures cristallines de RCPGs liant des ligands diffusibles a offert une opportunité de raffiner à une résolution atomique les modèles des mécanismes de transduction des signaux. Dans la première partie de cette thèse, nous avons donc exploré les déterminants de la signalisation du récepteur prototypique β2-adrénergique (β2AR), induite par les β-bloqueurs. En ne tenant compte que de leur efficacités sur le β2AR dans les voies de l'adénylate cyclase (AC) et des protéines kinases activées par les facteurs mitogéniques (MAPK), les β-bloqueurs peuvent être classés en 3 groupes distincts (agoniste inverse AC / agoniste MAPK, antagoniste neutre AC / agoniste MAPK et agoniste inverse AC / agoniste inverse MAPK). Afin de déterminer le lien entre leur efficacité et leur mode de liaison, nous avons réalisé des expériences d'arrimages moléculaires in silico entre des β-bloqueurs de chacun des groupes et la structure cristalline du β2AR liée au carazolol. De manière intéressante, les ligands à l'intérieur d'un groupe partagent un mode de liaison, alors que ceux des ligands entre les groupes divergent, suggérant que le mode de liaison des β-bloqueurs pourrait être utilisé pour prédire leur l'efficacité. En accord avec cette hypothèse, nous avons prédit et confirmé l'efficacité agoniste MAPK du carazolol, un inverse agoniste AC du β2AR se liant au récepteur de manière similaire au groupe inverse agoniste AC / agoniste MAPK. De manière intéressante, le groupement aryl des ligands agonistes inverses agonistes AC / agoniste MAPK, le seul groupement chimique variable de ce groupe, est prédite pour lier la région des 3e et 5e hélices transmembranaires (TM3 et TM5). Nous avons donc émis l'hypothèse que cette région pourrait être un déterminant de l'efficacité de ces ligands. En accord avec cette dernière, la mutation de 2 résidus (T118I, S203A) localisés proches du site de liaison des groupements aryls des β-bloqueurs, prévient l'efficacité agoniste inverse de l'ICI-118551 sur la voie de l'AC sans affecter l'efficacité d'un agoniste, indiquant que cette région est importante pour la transmission de l'effet agoniste inverse, du moins sur la voie de l'AC. Les βarrs sont des protéines d'échafaudage qui coordonnent la formation de complexes avec plusieurs dizaines d'effecteurs de signalisation. Originalement identifiées pour leur rôle dans la désensibilisation et l'internalisation des RCPGs, elles sont aussi d'importants effecteurs de la signalisation des RCPGs indépendante des protéines G hétérotrimériques. Cependant, contrairement aux protéines G hétérotrimériques, il n'existe que peu d'outils pour les étudier. Ainsi, la deuxième partie de la thèse est dédiée au développement d'outils pour l'étude des βarrs. À cette fin, nous avons d'abord tenté de transposer une méthode de mesure de l'interaction entre 2 protéines par la technologie de transfert d'énergie de bioluminescence par résonance (BRET) en microscopie et chez des souris transgéniques afin de mesurer de manière subcellulaire et dans un contexte natif l'engagement de la βarr à des RCPGs. Ainsi, nous avons établi les preuves de principe que le BRET peut être utilisé pour localiser l'interaction entre la βarr et le récepteur de la vasopressine de type 2 (V2R) sur une cellule au microscope et pour détecter l'interaction entre la βarr et le β2AR sur des tissus de souris transgéniques exprimant ces protéines fusionnées avec des partenaires BRET. Finalement, il n'existe aucun inhibiteur pharmacologique ciblant les βarrs. Ainsi, grâce à la combinaison d'approches de criblage virtuel sur un modèle de la structure des βarrs et d'essais de validation cellulaire, nous avons développé un inhibiteur pharmacologique des βarrs. À l'aide de cet outil, nous avons confirmé l'implication des βarrs dans l'activation des MAPK par le V2R, mais aussi montré un nouveau rôle des βarrs dans le recyclage du β2AR. Les connaissances et outils développés dans cette thèse permettront de mieux comprendre les déterminants moléculaires de la signalisation des RCPGs et entre autres, grâce à des nouvelles approches pour étudier le rôle cellulaire et physiologique des βarrs. / G Protein-Coupled Receptors (GPCR) are members of the largest family of membrane protein in the human genome. They transduce the signal from a variety of stimuli like odors, ions, hormones and neurotransmitters, inside the cells. By binding directly to the receptors, these molecules stabilize activating conformational changes that are allosterically propagated through transmembrane to intracellular domains. Effectors like heterotrimeric G protein and β-arrestins (βarrs) are then engaged by activated receptors and trigger a cascade of signalling events leading to a cellular response. Recently, the resolution of the crystal structure of GPCR that bind to freely diffusible ligands provided the opportunity to refine at an atomic level the models describing the mecanisms of receptor signal transduction. In the first section of this thesis, we have explored the determinants of the prototypical β2-adrenergic receptor (β2AR) signalling induced by β-blockers. Given their efficacy on Adenylate Cyclase (AC) and Mitogen-Activated Protein Kinase (MAPK) pathways, β-blockers can be classified within 3 signalling groups (AC inverse agonist / MAPK agonist, AC neutral antagonist / MAPK agonist and inverse agonist for AC and MAPK). In order to gain insight on the relation between their efficacy and binding mode, we performed in silico binding experiments between β-blockers from each group and the β2AR crystal structure bound to carazolol. Interestingly, ligands within a group share similar binding mode in contrast to those of different groups, suggesting that β-blockers binding mode could be used to predict their efficacy. In accordance to this hypothesis, we have predicted and confirmed that carazolol, an AC inverse agonist that bind to β2AR in a similar way than the AC inverse agonist / MAPK agonist group, is indeed an agonist for MAPK pathway. Moreover, aryl chemical function from AC inverse agonist / MAPK agonist ligands, barely the only variable structure feature of this group, was predicted to bind β2AR nearby the transmembrane helices 3 and 5 (TM3 and TM5). We thus have predicted that this region would be a determinant of the AC inverse agonist / MAPK agonist ligand efficacy. Accordingly, we found that mutation of 2 residues (T118I, S203A) close to the aryl moiety binding site prevents inverse agonist efficacy of ICI-118551 on AC pathway, without affecting agonist efficacy, indicating that this receptor region is important for the efficacy of these group of β-blockers, at least on AC inverse agonism.βarrs are scaffolding proteins that coordinate protein complex formation with dozen of signalling effectors. First identified for their role on GPCR desensitization and internalization, βarrs are also an important heterotrimeric G protein independent GPCR signalling effectors. However, in contrast to heterotrimeric G protein, only a few tools are available for their study. Thus, the second section of this thesis aim at developing tools for the study of βarrs. For this purpose, we had attempted to transpose a method to measure protein-protein interaction that use Bioluminescence Resonance Energy Transfer (BRET) technology, in microscopy and in transgenic mice, in order to detect subcellular localization and in a native context the engagement of βarr to RCPGs. Thus, we have established a proof of principle that BRET can be combined with microscopy to locate an interaction between βarr and the type 2 vasopressin receptor (V2R) within a cell. Moreover, we have established a second proof of principle that we can detect βarrs recruitment to β2AR on cells extracted from tissues of transgenic mice expressing these proteins fused to BRET partner. Finally, there is no pharmacological inhibitor of βarrs. Thus, using a combination of virtual screening and cellular validation approches, we have developed the first pharmacological βarrs inhibitor. With this novel tool, we have confirmed the implication of βarrs in V2R-mediated MAPK activation, but also showed a new role of βarrs in β2AR recycling.The finding and the tools presented in this thesis should allow to better understand the molecular determinants of GPCR signalling, and among other things, by proposing new tools to study βarrs cellular and physiological roles.