Дисертації з теми "Phase selector"

Pour différentes raisons, la 5G domine actuellement l'actualité technologique. Les capacités de la 5G en termes de largeur de bande et de temps réel constitues un énorme potentiel sociétal en permettant pléthore d'applications nouvelles et inattendues. En effet, la bande de fréquence des ondes millimétriques se caractérise par une largeur de bande disponible qui peut prendre en charge des systèmes sans fil à haut débit pour les futurs systèmes de radiocommunication, y compris les systèmes cellulaires de cinquième génération et au-delà. Les fréquences d'exploitation des ondes millimétriques nécessitent généralement une plus grande ouverture d'antenne pour améliorer le bilan de liaison. Ces antennes se présentent généralement sous la forme de réseaux phasés, permettant la formation de faisceaux. Dans ce contexte, ce travail présente la conception et la mise en œuvre d'un déphaseur actif à 19,5 GHz pour la formation de faisceaux. Le circuit proposé est basé sur une architecture originale utilisant un oscillateur commandé en tension verrouillé par injection (ILVCO en Anglais) associé à un filtre polyphase suivi d'un circuit de sélection de phase et de son signe. La phase souhaitée dans la plage de ± 45° est synthétisée avec le circuit proposé en modifiant la tension de commande Vcntr de l’ILVCO pour un réglage fin et en modifiant les deux signaux de commandes du sélecteur de phase et de signe (S0, S2) pour un réglage grossier, ce qui engendre une variation de phase linéaire de 360°. D'après les résultats de la simulation post-layout, la plage de réglage de la fréquence d’oscillation libre du VCO varie de 17,89 GHz à 20,16 GHz. En outre, avec une puissance injectée de -8,5 dBm et une fréquence de 19,5 GHz, le déphaseur proposé consomme 20,47 mA sous une tension d'alimentation de 1,3 V. De plus, la puissance de sortie moyenne sur 50 Ω est de -15,58 dBm. Le circuit complet a une taille de 1,58 mm2, y compris les pads, et il est intégré sur un process BiCMOS SiGe:C 0,13 μm. Enfin, les résultats obtenus montrent que le déphaseur actif proposé s’avère un candidat potentiel pour les systèmes à réseau phasé utilisés pour la formation de faisceaux dans les applications 5G
For good reasons, 5G dominates technological news. The high-bandwidth and real-time capabilities of 5G have huge societal potential by enabling a plethora of new and unanticipated application cases. Indeed, the millimeter-wave frequency band is characterized by an available bandwidth that can support high-speed wireless systems for future radio communications systems, including 5th Generation cellular systems and beyond. The frequencies of operation at mm-wave generally requires larger antenna aperture to improve the channel budget at useful distances. These antennas are usually in the form of phased arrays, allowing beamforming to be performed. This work presents the design and implementation of a 19.5 GHz active phase shifter for beamforming in 5G applications. The proposed circuit is based on an original architecture using an injection-locked voltage-controlled oscillator (ILVCO) associated with a polyphase filter followed by a phase selection circuit and its sign. The desired phase in the range of ± 45° is synthesised with the proposed circuit by altering the control voltage Vcntr of an ILVCO for fine-tuning and modifying the two control signals of phase and sign selectors (S0, S2) for coarse tuning, resulting in a 360° linear phase variation. According to the post-layout simulation results, the frequency tuning range of the VCO varies from 17.89 GHz to 20.16 GHz in free-running mode. In addition, with an injected power of -8.5 dBm and a frequency of 19.5 GHz, the proposed phase shifter draws 20.47 mA from a 1.3 V supply voltage. Furthermore, the mean output power on 50 Ω load is found to be -15.58 dBm. The whole circuit has a chip size of 1.58 mm2 including the pads and it is integrated in a BiCMOS SiGe:C 0.13 μm process. Finally, the obtained results justify that the proposed active phase shifter is a relevant design for phased-array systems used for beamforming in 5G applications

La mémoire à changement de phase (PCM) s’inscrit dans la stratégie de développement de mémoires non-volatiles embarquées sur les nœuds technologiques avancés (sub 28nm). En effet, la mémoire Flash-NOR devient de plus en plus onéreuse à intégrer dans les technologies avec des diélectriques à forte permittivité et des grilles métalliques. Cette thèse a donc pour objectif principal de réaliser des véhicules de tests afin d’étudier un point mémoire novateur PCM + OTS et de proposer des solutions afin de combler ses lacunes et ses limites suivant les applications envisagées. L’étude a pour support deux technologies différentes le HCMOS9A et le P28FDSOI. La première sert de support pour le développement d’un véhicule de validation technologique du point mémoire OTS+PCM. La deuxième est, quant à elle, utilisée pour démontrer la surface obtenu avec un dimensionnement agressif du point mémoire. Enfin, un circuit de lecture optimisé pour ce point mémoire a été réalisé permettant la compensation des courants de fuites ainsi que la régulation des tensions de polarisations de la matrice au cours de la lecture
Phase change memory (PCM) is part of the strategy to develop non-volatiles memories embedded in advanced technology nodes (sub 28nm). Indeed, Flash-NOR memory is becoming more and more expensive to integrate in technologies with high permittivity dielectrics and metallic gates. The main objective of this thesis is therefore to realize tests vehicles in order to study an innovative PCM + OTS memory point and to propose solutions to fill its gaps and limitations according to the envisaged applications. The study is based on two different technologies: HCMOS9A and P28FDSOI. The first one is used as support for the development of a technological validation vehicle of the OTS+PCM memory point. The second one is used to demonstrate the surface obtained with an aggressive sizing of the memory point. Finally, an optimized readout circuit for this memory point has been realized allowing the compensation of leakage currents as well as the regulation of the bias voltages of the matrix during the reading

Thesis (M.S. in Management) Naval Postgraduate School, Dec. 2000.
"December 2000." Thesis advisor(s): Jeffrey Cuskey, Keith Snider. Includes bibliographical references (p. 111-114). Also available online.

Power consumption of smart cameras varies significantly between sleep mode and active mode, and a smart camera operates in sleep mode for 80 — 90% of time for typical use. To prolong the battery life of smart cameras, it is essential to increase the power converter efficiency for light load, while being able to manage heavy load. The power stage of traditional buck converter is optimized for maximum load, at the cost of light-load efficiency. Wei proposed a multiphase buck converter incorporating the baby-buck concept and optimum number of phases (ONP) control. This thesis research investigated Wei's multiphase buck converter to improve the light-load efficiency for smart cameras as the target application. The proposed two-phase buck converter aims to provide power for microprocessors of smart cameras. The input voltage of the converter is 5 V DC, and the output voltage is 1.2 V DC with power dissipation range of 25 mA (30 mW) for light load and 833 mA (1 W) for heavy load. Three methods are considered to improve light-load efficiency: adopting baby-buck concept, adapting ONP control for low-power range, and implementing a pulse frequency modulation (PFM) control scheme with discontinuous conduction mode (DCM) to lower switching frequency. The first method is to adopt the baby-buck concept through power stage design of each phase to optimize efficiency for a specific load range. The baby-buck phase is optimized for light load and the heavy-load phase is designed to handle the processors maximum power consumption. The second method performs phase selection from sensed load current information. Rather than have all phases active for heavy-load as in ONP control, optimum phase selection (OPS) control is introduced to adaptively select between phases based on load current. Due to low-power constraints, OPS is more efficient for the medium to heavy-load range. The transition between phases due to load change is also investigated. The third and final method implements PFM control with DCM to lower switching frequency and reduce switching and driving losses under light load. PFM is accomplished with a constant on-time (COT) valley current mode controller, which uses the inductor current information and output voltage to generate switching signals for both the top and bottom switches. The baby-buck phase enters DCM to lower switching frequency under very light load, while the heavy-load phase remains in continuous conduction mode (CCM) throughout its load range. The proposed two-phase buck converter is designed and prototyped using discrete components. Efficiency of the two-phase converter and a power loss breakdown for each block in the control scheme were measured. The efficiency ranges from 64% to 81% for light load ranging of 30 mW to 200 mW, and the efficiency ranges from 81% to 88% for heavy load ranging from 200 mW to 1 W. The majority loss is due to controllers, which are responsible for 37 % (8.6 mW) for light load of 60 mW and for 10.9 % (9 mW) for heavy load of 600 mW. The gate driver loss is considerable for heavy load of 600 mW, consuming 11.9% (9.8mW). The converter has a 10 mV overshoot voltage for a load step-down from 225 mA to 25 mA, and it has 65 mV overshoot voltage for a load step-up from 25 mA to 225 mA. Although, a fair comparison is difficult due to use of discrete parts for OPS control, the proposed converter shows reasonably good efficiency and performance.
Master of Science

The DC casting of 1000 series AI-Fe-Si alloys often results in the formation of a defect known as the Fir Tree Zone (FI'Z) caused by variations in the type of binary AI-Fe eutectic intennetallic phase. These include AI3Fe, which is the equilibrium phase, and ~Fe, AImFe and AlxFe which are all common metastable phases found in DC cast ingots. Variation in the solidification conditions across a DC cast ingot.in particular, the cooling rate and local solidification velocity, bring about transitions from one intennetallic phase to another. The composition of the alloy, especially the presence of minor trace elements is also known to affect the transitions, but its effect has been less well studied. Equipment was constructed which reliably simulated DC casting conditions and enabled the FfZ to be reproduced. Experiments were conducted to examine the effect of the concentration of Fe, Si (and Fe:Si ratio) and of low levels «0.04 wt %) of Mg, Ti, Ti-B, V and Mn on the occurrence of phases causing the defect. Intennetallic phases extracted from the matrix by dissolution in hot butanol were identified by XRD. It was found that presence of Ti-B grain refmer had a large effect on the intennetallic phase selection, whilst the other trace element additions had lesser effects. In order to understand the way in which each element was affecting phase selection, experiments were conducted using DSC and a Bridgman furnace to isolate the variables of cooling rate and growth velocity respectively. A curve fitting technique was used to obtain values of eutectic nucleation onset temperature from DSC data where the primary aluminium and eutectic peaks overlapped. A technique was developed to extract intennetallic particles from DSC samples for examination in the TEM. It was found that the addition Ti-B grain refmer affected the phase selection by altering the nucleation temperature. The addition of Mg was found to stabilise the equilibrium phase by its affect on both growth temperature an nucleation temperature The effect of Ti was less clear in that it stabilised the equilibrium phase in the DSC experiments but tended to stabilise the metastable phase in the Bridgman experiments.

Understanding of the interrelationship between structure, thermodynamic properties and phase diagrams is very useful for rationalizing the behavior of materials and development of predictive models, which can be used to optimize the composition of materials and their fabrication processes. The properties of materials are governed by its electronic and crystallographic structure. Chemical bonding determines the electronic structure of materials. Furthermore, the electronic structure plays a predominant role in determining the physical, electrical, magnetic, thermal and optical properties of materials. Crystal structure also influences most properties of materials. Since changes in thermodynamic variables such as temperature, pressure, and composition dramatically alter the physical properties of materials and its structure, it is desirable to study the thermodynamic stability of materials in conjunction with phase relations. Phase diagrams can indicate the ranges of pressure, temperature and chemical composition where specific phases and mixtures of phases are stable. If the Gibbs energies of all the phases involved are known, phase diagram can be computed using Gibbs energy minimization algorithms. In recent times, one of the important uses of thermodynamics in materials science has been in the computation of phase diagrams. To materials scientists phase diagrams are like maps to travelers. They guide the path through the composition space to find phases, fulfilling specific materials performance requirements. As phase diagrams are the graphic representations of minimizations of Gibbs energy under given constraints, computational thermodynamics significantly expands our capability to walk in the multi-component space of engineering materials. High-temperature phase-equilibrium studies, thermodynamics and materials processing have had a close relationship over a number of decades. Successful utilization of ceramic materials under different environmental conditions at high temperatures requires accurate thermodynamic data. Focus of the present investigation is to obtain correct phase relations and accurate thermodynamic data in selected technologically important ceramic oxide systems in which the data are either not available or are inconsistent. Based on the experimental data, different types of phase diagrams are computed for the systems of contemporary relevance. After a brief introduction, Chapter 1 discusses the brief overview of the experimental techniques available for determining the phase relations and thermodynamic properties at high temperatures and the methods used in this study. The chapter reviews the possible sources of errors in experimental techniques and tests for correct functioning. In Chapter 2, systematic studies on high-temperature phase equilibria and thermodynamic properties of compounds in the ternary systems Ln-Pd-O (Ln = La, Pr, Eu, Gd, Tb, Dy, Ho and Er) are presented. Some of the ternary oxides on the Ln-Pd-O systems have potential application in catalysis and electrochemistry. To optimize the parameters for the synthesis and to understand the behavior of the catalysts, it is useful to have information on the thermodynamic stability domain of each compound. Quantitative information on the stability of the ternary oxides is also useful for assessing the interaction of metal Pd with ceramic compounds containing rare-earth elements under different environments. Furthermore, the thermodynamic data are beneficial for the design of processes for the recovery of rare earth and precious metals from scrap. There is very little thermodynamic and phase diagram information on the Ln-Pd-O systems. Isothermal sections of phase diagram for the ternary system La-Pd-O at 1200 K and for the systems Ln-Pd-O (Ln = Pr, Eu, Gd, Tb, Dy, Ho and Er) at 1223 K, were established by the isothermal equilibration technique at high temperatures. Phases were identified after quenching by optical and scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectroscopy (EDS). Based on the phase relations, the thermodynamic properties of ternary interoxide compounds were determined by the solid-state galvanic cell technique over a range of temperature between 925 - 1400 K. An advanced version of the solid-state cell incorporating a buffer electrode was used for high temperature thermodynamic measurements. The function of the buffer electrode, placed between reference and working electrodes, was to absorb the electrochemical flux of the mobile species through the solid electrolyte caused by trace electronic conductivity. The buffer electrode prevented polarization of the measuring electrode and ensured accurate data. Yttria-stabilized zirconia was used as the solid electrolyte and pure oxygen gas at a pressure of 0.1 MPa as the reference electrode. These novel features enhanced the accuracy of thermodynamic data. From electrochemical measurements, the standard enthalpies of formation of these oxides from elements and their standard entropies at 298.15 K were also evaluated. The variation of the lattice parameters and unit cell volume as a function of rare earth atomic number for the three ternary compounds Ln4PdO7, Ln2PdO4 (Ln = La, Pr, Nd, Sm, Eu, Gd) and Ln2Pd2O5 (Ln = La to Er) are discussed. The systematic variations of thermodynamic properties of all the ternary compounds as a function of rare earth atomic number are presented and correlated with structural features. Thermodynamic and structural parameters of uninvestigated Ln-Pd-O systems (Ln = Ce, Pm) can be obtained by interpolation. Based on the thermodynamic information obtained in this study and auxiliary data on binary compounds available in the literature, different types of phase diagrams, isothermal oxygen potential diagrams, isobaric phase diagrams, isothermal two dimensional and three-dimensional chemical potential diagrams for the systems Ln-Pd-O (Ln = La, Pr, Eu, Gd, Tb, Dy, Ho and Er) are constructed. Chapter 3 contains the studies on partial phase diagrams of the systems M-Ru-O (M = Ca and Sr) at 1300 K and determination of Gibbs energies of formation of calcium and stronsium ruthenates in the temperature range from 925 to 1350 K using solid-state cells with yttria-stabilized zirconia as the electrolyte and Ru + RuO2 as the reference electrode. Gibbs energies, enthalpies and entropies of formation of calcium and strontium ruthenates from their component binary oxides were deduced. The standard enthalpies of formation of these oxides from elements and their standard entropies at 298.15 K were also evaluated. Based on the thermodynamic data obtained in this study and auxiliary information from the literature, the three dimensional representation of oxygen potential diagram for the M-Ru-O systems (M = Ca and Sr) as a function of composition and temperature are computed. The purpose of this chapter is to determine the thermodynamic stability of alkaline earth metal ruthenates in the perovskite related layered system Mn+1RunO3n+1 (n = 1, 2, and ¥ for Ca-Ru-O system and n = 1, 2, 3 and µ for Sr-Ru-O system) since these calcium and stronsium ruthenates have interesting magnetic and electronic device applications. Moreover, there is no literature available for thermodynamic properties on first and second members of the Ruddelsdon-Popper (R-P) series in Ca-Ru-O system, Ca2RuO4, Ca3Ru2O7 and third member of R-P series in Sr-Ru-O system, Sr4Ru3O10. Some of the available literature information on thermodynamic properties for other compounds of R-P series in Mn+1RunO3n+1 (M = Ca, Sr) are found to be based on incorrect assumptions and erroneous calculation. Thus, this chapter provides the complete thermodynamic information for all the electronically and magnetically applicable alkaline earth metal ruthenates for optimizing the deposition condition in device fabrications. Chapter 4 gives the structure-properties correlations of 2-3 spinel compounds and spinel-corundum equilibria for the system NiO-Al2O3-Cr2O3 at 1373 K. Nickel, aluminum and chromium are important base-constituent elements of high-temperature oxidation-resistant alloys. A spinel phase is usually found in the protective scale formed on the surface of the alloys. There is no thermodynamic data on spinel solid solution NiAl2O4-NiCr2O4. Thus, the phase relations and mixing properties of the spinel solid solution have been determined in this chapter. The inter-crystalline ion-exchange equilibrium between NiAl2+2xO4+3x-NiCr2O4 spinel solid solution and Al2O3-Cr2O3 solid solution with corundum structure in pseudo-ternary system NiO-Al2O3-Cr2O3 have been determined by the conventional tie-line rotation method at 1373 K. The nonstoichiometry of NiAl2+2xO4+3x has been taken into consideration. Lattice parameters were used to obtain the compositions of the corundum and spinel solid solutions at equilibrium. Formation of homogeneous solid solutions and attainment of equilibrium were confirmed by X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDS). From the experimental tie-line information and thermodynamic data on Al2O3-Cr2O3 solid solution available in the literature, the activities in the spinel solid solution were derived by using a modified Gibbs-Duhem integration technique. Gibbs energy of mixing of the spinel solid solution has been calculated from the derived activity data. Since high temperature data generation is expensive and time consuming, it is useful to develop models, which relate thermodynamic properties to electronic and crystallographic structure, leading to predictive modeling of mixing properties. By comparing the results from models with experimental information, one can evolve methodologies for the prediction of the properties of uninvestigated system. A model can be used to discriminate among conflicting experimental data and extrapolate the data into regions where direct measurements are lacking or difficult to perform. In this chapter, a model approach has also been considered to analyze the activity-composition relationship in the NiAl2O4-NiCr2O4 spinel solid solution in terms of the intra-crystalline exchange of cations between the tetrahedral and octahedral sites of the spinel structure governed by site preference energies of the cations. Since Ni2+ and Cr3+ ion in tetrahedral coordination exhibits Jahn-Teller distortion, an entropy corresponding to randomization of the distortion in the cubic phase has been incorporated in the cation distribution model. The thermodynamic mixing properties of stoichiometric spinel solid solution NiAl2O4-NiCr2O4 in terms of one mole of mixing species were computed at 1373 K. The strain energy caused by size mismatch was added as a separate term to the Gibbs energy of mixing using empirical relationship between enthalpy of mixing for a pair of ions and the difference in their ionic volumes. Madelung constant and electrostatic contribution of energy of mixing of the spinel solid solution have also been computed. Comparison of Gibbs energy of mixing calculated using the cation mixing model for the stoichiometric spinel solid solution NiAl2O4-NiCr2O4 with that of the experimental tie-line data for nonstoichiometric spinel solid solution NiAl2+2xO4+3x-NiCr2O4 were included in this chapter. The thermodynamic mixing properties obtained in this study would be helpful in understanding the formation of complex spinel protective layers on alloys containing nickel, aluminium and chromium in high-temperature applications. The summary of the important finding and the conclusions arrived at on the basis of results obtained from the present investigations are presented in Chapter 5.

Understanding of the interrelationship between structure, thermodynamic properties and phase diagrams is very useful for rationalizing the behavior of materials and development of predictive models, which can be used to optimize the composition of materials and their fabrication processes. The properties of materials are governed by its electronic and crystallographic structure. Chemical bonding determines the electronic structure of materials. Furthermore, the electronic structure plays a predominant role in determining the physical, electrical, magnetic, thermal and optical properties of materials. Crystal structure also influences most properties of materials. Since changes in thermodynamic variables such as temperature, pressure, and composition dramatically alter the physical properties of materials and its structure, it is desirable to study the thermodynamic stability of materials in conjunction with phase relations. Phase diagrams can indicate the ranges of pressure, temperature and chemical composition where specific phases and mixtures of phases are stable. If the Gibbs energies of all the phases involved are known, phase diagram can be computed using Gibbs energy minimization algorithms. In recent times, one of the important uses of thermodynamics in materials science has been in the computation of phase diagrams. To materials scientists phase diagrams are like maps to travelers. They guide the path through the composition space to find phases, fulfilling specific materials performance requirements. As phase diagrams are the graphic representations of minimizations of Gibbs energy under given constraints, computational thermodynamics significantly expands our capability to walk in the multi-component space of engineering materials. High-temperature phase-equilibrium studies, thermodynamics and materials processing have had a close relationship over a number of decades. Successful utilization of ceramic materials under different environmental conditions at high temperatures requires accurate thermodynamic data. Focus of the present investigation is to obtain correct phase relations and accurate thermodynamic data in selected technologically important ceramic oxide systems in which the data are either not available or are inconsistent. Based on the experimental data, different types of phase diagrams are computed for the systems of contemporary relevance. After a brief introduction, Chapter 1 discusses the brief overview of the experimental techniques available for determining the phase relations and thermodynamic properties at high temperatures and the methods used in this study. The chapter reviews the possible sources of errors in experimental techniques and tests for correct functioning. In Chapter 2, systematic studies on high-temperature phase equilibria and thermodynamic properties of compounds in the ternary systems Ln-Pd-O (Ln = La, Pr, Eu, Gd, Tb, Dy, Ho and Er) are presented. Some of the ternary oxides on the Ln-Pd-O systems have potential application in catalysis and electrochemistry. To optimize the parameters for the synthesis and to understand the behavior of the catalysts, it is useful to have information on the thermodynamic stability domain of each compound. Quantitative information on the stability of the ternary oxides is also useful for assessing the interaction of metal Pd with ceramic compounds containing rare-earth elements under different environments. Furthermore, the thermodynamic data are beneficial for the design of processes for the recovery of rare earth and precious metals from scrap. There is very little thermodynamic and phase diagram information on the Ln-Pd-O systems. Isothermal sections of phase diagram for the ternary system La-Pd-O at 1200 K and for the systems Ln-Pd-O (Ln = Pr, Eu, Gd, Tb, Dy, Ho and Er) at 1223 K, were established by the isothermal equilibration technique at high temperatures. Phases were identified after quenching by optical and scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectroscopy (EDS). Based on the phase relations, the thermodynamic properties of ternary interoxide compounds were determined by the solid-state galvanic cell technique over a range of temperature between 925 - 1400 K. An advanced version of the solid-state cell incorporating a buffer electrode was used for high temperature thermodynamic measurements. The function of the buffer electrode, placed between reference and working electrodes, was to absorb the electrochemical flux of the mobile species through the solid electrolyte caused by trace electronic conductivity. The buffer electrode prevented polarization of the measuring electrode and ensured accurate data. Yttria-stabilized zirconia was used as the solid electrolyte and pure oxygen gas at a pressure of 0.1 MPa as the reference electrode. These novel features enhanced the accuracy of thermodynamic data. From electrochemical measurements, the standard enthalpies of formation of these oxides from elements and their standard entropies at 298.15 K were also evaluated. The variation of the lattice parameters and unit cell volume as a function of rare earth atomic number for the three ternary compounds Ln4PdO7, Ln2PdO4 (Ln = La, Pr, Nd, Sm, Eu, Gd) and Ln2Pd2O5 (Ln = La to Er) are discussed. The systematic variations of thermodynamic properties of all the ternary compounds as a function of rare earth atomic number are presented and correlated with structural features. Thermodynamic and structural parameters of uninvestigated Ln-Pd-O systems (Ln = Ce, Pm) can be obtained by interpolation. Based on the thermodynamic information obtained in this study and auxiliary data on binary compounds available in the literature, different types of phase diagrams, isothermal oxygen potential diagrams, isobaric phase diagrams, isothermal two dimensional and three-dimensional chemical potential diagrams for the systems Ln-Pd-O (Ln = La, Pr, Eu, Gd, Tb, Dy, Ho and Er) are constructed. Chapter 3 contains the studies on partial phase diagrams of the systems M-Ru-O (M = Ca and Sr) at 1300 K and determination of Gibbs energies of formation of calcium and stronsium ruthenates in the temperature range from 925 to 1350 K using solid-state cells with yttria-stabilized zirconia as the electrolyte and Ru + RuO2 as the reference electrode. Gibbs energies, enthalpies and entropies of formation of calcium and strontium ruthenates from their component binary oxides were deduced. The standard enthalpies of formation of these oxides from elements and their standard entropies at 298.15 K were also evaluated. Based on the thermodynamic data obtained in this study and auxiliary information from the literature, the three dimensional representation of oxygen potential diagram for the M-Ru-O systems (M = Ca and Sr) as a function of composition and temperature are computed. The purpose of this chapter is to determine the thermodynamic stability of alkaline earth metal ruthenates in the perovskite related layered system Mn+1RunO3n+1 (n = 1, 2, and ¥ for Ca-Ru-O system and n = 1, 2, 3 and µ for Sr-Ru-O system) since these calcium and stronsium ruthenates have interesting magnetic and electronic device applications. Moreover, there is no literature available for thermodynamic properties on first and second members of the Ruddelsdon-Popper (R-P) series in Ca-Ru-O system, Ca2RuO4, Ca3Ru2O7 and third member of R-P series in Sr-Ru-O system, Sr4Ru3O10. Some of the available literature information on thermodynamic properties for other compounds of R-P series in Mn+1RunO3n+1 (M = Ca, Sr) are found to be based on incorrect assumptions and erroneous calculation. Thus, this chapter provides the complete thermodynamic information for all the electronically and magnetically applicable alkaline earth metal ruthenates for optimizing the deposition condition in device fabrications. Chapter 4 gives the structure-properties correlations of 2-3 spinel compounds and spinel-corundum equilibria for the system NiO-Al2O3-Cr2O3 at 1373 K. Nickel, aluminum and chromium are important base-constituent elements of high-temperature oxidation-resistant alloys. A spinel phase is usually found in the protective scale formed on the surface of the alloys. There is no thermodynamic data on spinel solid solution NiAl2O4-NiCr2O4. Thus, the phase relations and mixing properties of the spinel solid solution have been determined in this chapter. The inter-crystalline ion-exchange equilibrium between NiAl2+2xO4+3x-NiCr2O4 spinel solid solution and Al2O3-Cr2O3 solid solution with corundum structure in pseudo-ternary system NiO-Al2O3-Cr2O3 have been determined by the conventional tie-line rotation method at 1373 K. The nonstoichiometry of NiAl2+2xO4+3x has been taken into consideration. Lattice parameters were used to obtain the compositions of the corundum and spinel solid solutions at equilibrium. Formation of homogeneous solid solutions and attainment of equilibrium were confirmed by X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDS). From the experimental tie-line information and thermodynamic data on Al2O3-Cr2O3 solid solution available in the literature, the activities in the spinel solid solution were derived by using a modified Gibbs-Duhem integration technique. Gibbs energy of mixing of the spinel solid solution has been calculated from the derived activity data. Since high temperature data generation is expensive and time consuming, it is useful to develop models, which relate thermodynamic properties to electronic and crystallographic structure, leading to predictive modeling of mixing properties. By comparing the results from models with experimental information, one can evolve methodologies for the prediction of the properties of uninvestigated system. A model can be used to discriminate among conflicting experimental data and extrapolate the data into regions where direct measurements are lacking or difficult to perform. In this chapter, a model approach has also been considered to analyze the activity-composition relationship in the NiAl2O4-NiCr2O4 spinel solid solution in terms of the intra-crystalline exchange of cations between the tetrahedral and octahedral sites of the spinel structure governed by site preference energies of the cations. Since Ni2+ and Cr3+ ion in tetrahedral coordination exhibits Jahn-Teller distortion, an entropy corresponding to randomization of the distortion in the cubic phase has been incorporated in the cation distribution model. The thermodynamic mixing properties of stoichiometric spinel solid solution NiAl2O4-NiCr2O4 in terms of one mole of mixing species were computed at 1373 K. The strain energy caused by size mismatch was added as a separate term to the Gibbs energy of mixing using empirical relationship between enthalpy of mixing for a pair of ions and the difference in their ionic volumes. Madelung constant and electrostatic contribution of energy of mixing of the spinel solid solution have also been computed. Comparison of Gibbs energy of mixing calculated using the cation mixing model for the stoichiometric spinel solid solution NiAl2O4-NiCr2O4 with that of the experimental tie-line data for nonstoichiometric spinel solid solution NiAl2+2xO4+3x-NiCr2O4 were included in this chapter. The thermodynamic mixing properties obtained in this study would be helpful in understanding the formation of complex spinel protective layers on alloys containing nickel, aluminium and chromium in high-temperature applications. The summary of the important finding and the conclusions arrived at on the basis of results obtained from the present investigations are presented in Chapter 5.

This thesis presents modifications to and optimisations of a cluster beam source, one application being the generation of large area catalysis samples. A major modification to the cluster source also enabled coating of clusters in a new way. The impact of Pd\(_5\)\(_6\)\(_1\), Pd\(_5\)\(_5\)and Pd\(_4\) clusters (1, 1.5 and 1 keV) on a thin material film evaporated onto a solid argon matrix led to deposition of large, 5-40 nm diameter, irregularly shaped particles. Furthermore, Pd\(_9\)\(_2\)\(_3\) and Pd\(_2\)\(_0\)\(_0\)\(_0\) clusters, with both 0.5 and 1.5 keV impact energies, have been coated in-flight by impact on the thin film/solid matrix, as verified from the increase in diameters of the deposited particles and the detection of Pd signal by EELS. MoS\(_2\) nano pillar catalyst samples were etched using size-selected metal etch masks. Catalyst samples of ordered MoS\(_2\) nano pillars were fabricated using NSL and a novel way to apply nano spheres was developed. Different etch recipes were used to obtain nano pillars with different diameters and heights; these recipes were also applied to reference MoS\(_2\) samples without etch masks. Generally, the reference catalyst samples, with their roughened surfaces, showed higher HER activity than their corresponding ordered MoS2 nano pillar catalyst samples.

Le développement majeur de la thèse a été consacré au problème d’optimisation du choix de dose dans les essais de recherche de dose, en phase II. Nous avons considéré ce problème sous l’angle des fonctions d’utilité. Nous avons alloué une valeur d’utilité aux doses, le problème pour le sponsor étant de trouver la meilleure dose, c’est-à-dire celle dont l’utilité est la plus élevée.Dans ce travail, nous nous sommes limités à une seule fonction d’utilité, intégrant deux composantes: une composante liée à l’efficacité (la POS=puissance d’un essai de phase III de 1000 patients de cette dose contre placebo) et une autre liée à la safety. Pour cette dernière, nous avons choisi de la caractériser par la probabilité prédictive d’observer un taux de toxicité inférieur ou égal à un certain seuil (que nous avons fixé à 0.15) en phase III (toujours pour un essai de 1000 patients au total). Cette approche a l’avantage d’être similaire aux concepts utilisés dans les essais de phase I en oncologie qui ont notamment pour objectif la recherche de la dose liée à une toxicité limite (notion de ”Dose limiting Toxicity”).Nous avons retenu une approche bayésienne pour l’analyse des données de la phase II.Mis à part les avantages théoriques connus de l’approche bayésienne par rapport à l’approche fréquentiste (respect du principe de vraisemblance, dépendance moins grande aux résultats asymptotiques, robustesse), nous avons choisi l’approche bayésienne pour plusieurs raisons:• Combinant, par définition même de l’approche bayésienne, une information a priori avec les données disponibles, elle offre un cadre plus flexible la prise de décision du sponsor: lui permettant notamment d’intégrer de manière plus ou moins explicite les informations dont il dispose en dehors de l’essai de la phase II.• L’approche bayésienne autorise une plus grande flexibilité dans la formalisation des règles de décision.Nous avons étudié les propriétés des règles de décisions par simulation d’essais de phase II de différentes tailles: 250, 500 et 1000 patients. Pour ces deux derniers design nous avons aussi évalué l’intérêt de d’effectuer une analyse intermédiaire lorsque la moitié des patients a été enrôlée (c’est-à-dire avec respectivement les premiers 250 et 500 patients inclus). Le but était alors d’évaluer si, pour les essais de phase II de plus grande taille, s’autoriser la possibilité de choisir la dose au milieu de l’étude et de poursuivre l’étude jusqu’au bout si l’analyse intermédiaire n’est pas concluante permettait de réduire la taille de l’essai de phase II tout en préservant la pertinence du choix de dose final
The main development of the thesis was devoted to the problem of dose choice optimization in dose-finding trials, in phase II. We have considered this problem from the perspective of utility functions. We have allocated a utility value to the doses itself, knowing that the sponsor’s problem was now to find the best dose, that is to say, the one having the highest utility. We have limited ourselves to a single utility function, integrating two components: an efficacy-related component (the PoS = the power of a phase III trial - with 1000 patients - of this dose versus placebo) and a safety-related component. For the latter, we chose to characterize it by the predictive probability of observing a toxicity rate lower or equal to a given threshold (that we set to 0.15) in phase III (still for a trial of 1000 patients in total). This approach has the advantage of being similar to the concepts used in phase I trials in Oncology, which particularly aim to find the dose related to a limiting toxicity (notion of "Dose limiting Toxicity").We have adopted a Bayesian approach for the analysis of phase II data. Apart from the known theoretical advantages of the Bayesian approach compared with the frequentist approach (respect of the likelihood principle, less dependency on asymptotic results, robustness), we chose this approach for several reasons:• It provides a more flexible framework for the decision-making of the sponsor because it offers the possibility to combine (by definition of the Bayesian approach) a priori information with the available data: in particular, it offers the possibility to integrate, more or less explicitly, the information available outside the phase II trial.• The Bayesian approach allows greater flexibility in the formalization of the decision rules.We studied the properties of decision rules by simulating phase II trials of different sizes: 250, 500 and 1000 patients. For the last two designs (500 and 1000 patients in phase II), we have also evaluated the interest of performing an interim analysis when half of the patients are enrolled (i.e. with the first 250and the first 500 patients included respectively). The purpose was then to evaluate whether or not, for larger phase II trials, allowing the possibility of choosing the dose in the middle of the study and continuing the study to the end if the interim analysis is not conclusive, could reduce the size of the phase II trial while preserving the relevance of the final dose choice

The popularity of capillary electrophoresis (CE) as a separation technique has been established over the years. CE offers the advantages of high resolution, high separation efficiency, fast approaches of method development, a range of operational modes and low consumption of reagents. The strategy employed here for the development of chromatographic separations involved the utilization of experimental designs, multi-linear regression and response surface methodology to build empirical models that related the chromatographic quality to the factors influencing the separation. Separation of Nitrofuran antibiotics (NFAs) and their metabolites (NFMs) by using micellar electrokinetic capillary chromatography was successfully completed. The best conditions found to give optimum resolution from the optimization study was pH 9.0, 80 mM SDC concentration, 16 kV with running buffer consisting of 20 mM borate and 20 mM phosphate concentration using a 73 cm x 75 ƒÝm column, resulting in completely resolved NFAs and NFMs within 16 min. It is interesting that all the compounds can be reliably separated with the one mixture, and single CE condition. Whilst all antibiotics have shorter migration time than their respective derivatised metabolites, as a group apart from nitrofurantoin the antibiotics elute before the metabolites. The analytical figures of merit for CE analysis exhibited excellent reproducibility of absolute and relative migration times, and acceptable reproducibility of relative response areas. Successful separation of metabolite derivatives was achieved when the developed method was applied to a spiked prawn sample. The chiral separation of Triadimenol was successfully completed using micellar electrokinetic capillary chromatography. The best conditions found to give optimum resolution from the optimisation study were pH 6.0, 20% methanol, 50 mM SDS concentration, 18 kV with running buffer consisting of 20 mM borate and 20 mM phosphate concentration using a 64.5 cm x 50 ƒÝm column, resulted in baseline resolution of all Triadimenol isomers within 18 min. The optimised separation conditions were applied to a blank grape sample and to a spiked grape sample. No peaks were observed in the blank grape sample whereas the spiked grape sample had two diastereoismer peaks with poor detection sensitivity. Increase in detection sensitivity is necessary to determine the possibility of resolution of all the isomers of Triadimenol, in the spiked grape sample and the blank. Online preconcentration techniques were attempted to for Triadimenol isomer separation. When using online preconcentration technique of sweeping, a 30-fold increase in detection sensitivity of Triadimenol was observed compared to MEKC mode. However enantiomer separation was not possible with sulfated-£]-CD chiral selector. The best conditions were found to be pH 2.5, 50 mM SDS concentration, -20 kV with running buffer consisting of 20 mM phosphate concentration, using a 64.5 cm x 50 ƒÝm column, resulting in diastereoisomer separation within 8 min. Final stage of the project was to create stationary phase beds in capillaries and micro-channels that could be removed and re-created, thus providing a fresh stationary phase. The replaceable stationary phase (RSP) can be used as an operating mode of CE/CEC. Preparation of reversible stationary phase (RSP) inside the capillary column was successfully performed using low methoxy pectin (LMP). LMP renders a capability of reversible thermogelation. Electroosmotic flow (EOF) and sufficient hydrophobicity of LMP gel allow separation of analyates. The porosity of LMP RSP was adequate to support EOF. Successful separation with good reproducibility of areas and migration times was obtained for Caffeine, Aspartame, Benzoic acid, Saccharine (CABS) mixture and NFAs. After performing continuous analyses, the aging of RSP was observed. Temperature was the ¡¥switch¡¦, which applied to remove aged RSP. RSP was recreated for further analysis of analytes. RSP was UV transparent, capable of handling various analytes and diff erent buffer electrolytes including aqueous-organic solvents.

In nature, non-covalent interactions are as important and dynamic as they are elusive. As such, the study of non-covalent interactions both in vivo and in vitro has proven to be challenging. Given the potential benefits of elucidating protein-protein, ligand-receptor, and other biologically relevant interactions, the development of methodologies for the study of non-covalent interactions is an attractive goal.Biologically encoded protein and peptide libraries that connect the genotypic information with the expressed phenotype have emerged in recent years as powerful methods for studying non-covalent interactions. One of the quintessential platforms for the creation of such libraries is phage display. In phage display, the connection between genetic information and the corresponding protein allows for the iterative isolation and amplification of library members that possess a desired function. Hence, an in vitro selection can be used to isolate epitopes that bind to desired targets or display specific attributes.We have sought to develop novel phage display methodologies that have the potential to expand the scope of this in vitro selection platform. Specifically, we developed a method for the non-covalent attachment of a small molecule ligand to a cyclic peptide library. This system localizes the phage display library to the ligand binding site, thus allowing for the translation of the selected cyclic peptides to a covalently tethered bivalent inhibitor.The first class of biological molecules that we chose to target with our methodology is the biologically and therapeutically important class of enzymes called protein kinases. In the first demonstration of this strategy, we were able to isolate cyclic peptide ligands for the model kinase PKA (cAMP-dependent protein kinase), which were subsequently translated to a bivalent inhibitor. This inhibitor showed both increased affinity and selectivity for PKA in relation to other protein kinases.In a separate project, we sought to develop a method for the isolation of small molecule-responsive mutants of a well-characterized protein scaffold from a phage display library. During these investigations, we discovered interesting homologous single-point mutations of the protein that resulted in large spherical oligomers that may mimic species relevant to the study of protein misfolding diseases such as Alzheimer's.

The diversity and range of the biological functions of non-coding RNA molecules (ncRNA) have only recently been realised, and phylogenetic analysis of the RNA genes that define these molecules can provide important insights into the evolutionary pressures acting on RNA genes, and can lead to a better understanding of the structure and function of ncRNA. An appropriate dataset is fundamental to any evolutionary analysis, and because existing RNA alignments are unsuitable, I describe a software pipeline to derive RNA gene datasets from genomic alignments. RNA gene prediction software has not previously been evaluated on such sets of known RNA genes, and I find that two popular methods fail to predict the genes in approximately half of the alignments. In addition, high numbers of predictions are made in flanking regions that lack RNA genes, and these results provide motivation for subsequent phylogenetic analyses, because a better understanding of RNA gene evolution should lead to improved methods of prediction. I analyse the RNA gene alignments with a range of evolutionary models of substitution and examine which models best describe the changes evident in the alignment. The best models are expected to provide more accurate trees, and their properties can also shed light on the evolutionary processes that occur in RNA genes. Comparing DNA and RNA substitution models is non-trivial however, because they describe changes between two different types of state, so I present a proof that allows models with different state spaces to be compared in a statistically valid manner. I find that a large proportion of RNA genes are well described by a single RNA model that includes parameters describing both nucleotides and RNA structure, highlighting the multiple levels of constraint that act on the genes. The choice of model affects the inference of a phylogenetic tree, suggesting that model selection, with RNA models, should be standard practice for analysis of RNA genes.

Solid phase extraction (SPE) has been developed as an alternative to liquid-liquid extraction (LLE) in the sample preparation process. The advantages of SPE over LLE are that it is a more useful, reliable tool for sample preparation, which offers greater selectivity. The selectivity of an SPE sorbent is vital for the isolation of analyte from a biological matrix containing a myriad of interferences. The use of conventional ion exchange SPE for such an extraction process might not be adequate due to the adverse effects of interfering ions. Metals immobilized on various modified silicas were investigated to determine if the addition of metals improved selectivity. The selectivity of these sorbents was studied by the extraction of analytes from high ionic strength matrices. Extraction selectivity was found to depend on different factors, including the type of bonded species, metal ions used and the analytes, counter ions, sample pH and elution solvent composition. Utilizing coordination complexation between analytes and immobilized metal ions, particularly when different phases are stacked, can increase selectivity for a particular analyte. Metals immobilized by ionic exchange sorbents were observed to retain analytes of tridentate chelation capability more than immobilized metals on bonded chelators. However, bonded chelators were observed to be advantageous because they more strongly retained metal ions, relative to ionic exchangers. The interactions of immobilized silver ions with unsaturated molecules utilizing SPE were investigated. Retention of silver ions was found dependent on the nature of bonded phase. The silver ions immobilized by coordination interactions showed weaker retention than silver immobilized by ionic interactions. Retention of alkenes by silver was found to have higher flow dependence, as compared to ionic exchange or ligand exchange processes. Retention of analytes was observed to depend on a variety of factors, including the type of bonded phase used for silver immobilization, the composition of the elution solvent, steric factors, the degree of unsaturation, the geometry and position of the double bonds of the analyte molecules. Extraction selectivity for geometrical isomers decreased when silver ions were immobilized by long chain cation exchangers versus those on conventional short chain cation exchangers.

A method was found for creating ordered nanoparticles whose size and theoretical order-disorder temperature are ideal for study in the TEM. Specifically FePt, NiPt, FeNiPt and AuCu nanoparticles were studied. We were able to show how a nanoparticle's size affects its order-disorder temperature (Tod). When the particles were around 6 nm in diameter there was a shift downward of the Tod of 10-15 percent compared to the bulk. While particles around 10 nm in diameter experienced a downward shift of 0-6 percent compared to the bulk. One can approximate that particles less than 10-15 nm in diameter would show significant decreases in order-disorder temperature. We confirmed that alumina prevents copper losses, compositions were well within percent error. In addition we showed that when the alumina used is thin enough the images are not adversely affected and charging is not an issue.

Cette thèse traite les problèmes statistiques suivants : la sélection de variables dans le modèle de régression linéaire en grande dimension, le clustering dans le modèle de mélange Gaussien, quelques effets de l'adaptabilité sous l'hypothèse de parcimonie ainsi que la simulation des processus Gaussiens.Sous l'hypothèse de parcimonie, la sélection de variables correspond au recouvrement du "petit" ensemble de variables significatives. Nous étudions les propriétés non-asymptotiques de ce problème dans la régression linéaire en grande dimension. De plus, nous caractérisons les conditions optimales nécessaires et suffisantes pour la sélection de variables dans ce modèle. Nous étudions également certains effets de l'adaptation sous la même hypothèse. Dans le modèle à vecteur parcimonieux, nous analysons les changements dans les taux d'estimation de certains des paramètres du modèle lorsque le niveau de bruit ou sa loi nominale sont inconnus.Le clustering est une tâche d'apprentissage statistique non supervisée visant à regrouper des observations proches les unes des autres dans un certain sens. Nous étudions le problème de la détection de communautés dans le modèle de mélange Gaussien à deux composantes, et caractérisons précisément la séparation optimale entre les groupes afin de les recouvrir de façon exacte. Nous fournissons également une procédure en temps polynomial permettant un recouvrement optimal des communautés.Les processus Gaussiens sont extrêmement utiles dans la pratique, par exemple lorsqu'il s'agit de modéliser les fluctuations de prix. Néanmoins, leur simulation n'est pas facile en général. Nous proposons et étudions un nouveau développement en série à taux optimal pour simuler une grande classe de processus Gaussiens
This PhD thesis deals with the following statistical problems: Variable selection in high-Dimensional Linear Regression, Clustering in the Gaussian Mixture Model, Some effects of adaptivity under sparsity and Simulation of Gaussian processes.Under the sparsity assumption, variable selection corresponds to recovering the "small" set of significant variables. We study non-asymptotic properties of this problem in the high-dimensional linear regression. Moreover, we recover optimal necessary and sufficient conditions for variable selection in this model. We also study some effects of adaptation under sparsity. Namely, in the sparse vector model, we investigate, the changes in the estimation rates of some of the model parameters when the noise level or its nominal law are unknown.Clustering is a non-supervised machine learning task aiming to group observations that are close to each other in some sense. We study the problem of community detection in the Gaussian Mixture Model with two components, and characterize precisely the sharp separation between clusters in order to recover exactly the clusters. We also provide a fast polynomial time procedure achieving optimal recovery.Gaussian processes are extremely useful in practice, when it comes to model price fluctuations for instance. Nevertheless, their simulation is not easy in general. We propose and study a new rate-optimal series expansion to simulate a large class of Gaussian processes

Thesis (Ph. D.)--School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 2005. Directed by Charles A. Eckert.
Charles L. Liotta, Committee Co-Chair ; Charles A. Eckert, Committee Chair ; Amyn S. Teja, Committee Member ; J. Carson Meredith, Committee Member ; Rigoberto Hernandez, Committee Member. Vita. Includes bibliographical references.

The behaviour of pharmaceutical excipients was studied in 2H, 3H-perfluoropentane (HPFP), a partially fluorinated liquid considered as a highly suitable model propellant for medicinal pressurized metered-dose inhalers (pMDIs) used in drug delivery to the lungs. The additives chosen belonged to three main categories: ethylene oxide oligomers and derivatives, chosen for their wide range of applications in pharmaceutical formulations, their harmlessness and low cost a hydrophobically modified cyclodextrin that shows potential for controlled release via host-guest interactions and some interesting solubility pattern in HPFP a family of tetrahydroxy diesters that act as unprecedented organogelators for mixtures of HPFP and a partially fluorinated alcohol co-solvent. By studying ethylene oxide oligomers and derivatives in HPFP and fully fluorinated analogue PFP, it was found that the solubility of the oligomers could be tuned by varying the nature of their end-group and the polarity of the fluorinated liquids employed. Methyl groups, either placed at the extremities, thus blocking the hydroxyl end-groups of dihydroxyl end-capped polyethylene glycols, or directly added on the polymer backbone, clearly enhanced their solubility. The Lower Critical Solution Temperature initially observed was either displaced or removed via the presence of the additional methyl groups. On the other hand, such phase separation could also be induced by the subsequent addition of PFP it is shown that such behaviours are dominated by end-group/solvent interactions. This study was published in two papers, Journal of Pharmacy and Pharmacology, 2008, 60: p. 593-599 and International Journal of Pharmaceutics, 2008, 362: p. 147-152. As an attractive formulation means, the hydrophobic triacetylated-P-cyclodextrin (TAjJCD) was chosen amongst others for its partial solubility in model propellant HPFP. The observation that various batches of the same chemical entity lead to highly different solubility profiles in HPFP resulted in the full characterisation of two existing polymorphs for this compound. The monitored conversion of one form into the other was achieved, and the amorphous form could be fully recrystallysed into the higher energy form via a limited seeding process. HPFP acted as a discriminator of the two crystalline forms. More details may be found in Journal of Physical Chemistry C, 2008,112: p. 14570-15578. The monitoring of the solubility via solvent properties, as seen in the first part, was also used in the formation of self-assembled supramolecular organogels. The addition of non-solvent HPFP to an initially stable sol composed of a small tetrahydroxy diesters in the fluoroalcohol 1H, 1H-heptafluorobutanol initiated their coming out of solution. However, instead of simply precipitating, the tetrahydroxy diester molecules self-assemble into long cylindrical fibres that form a 3-dimensional network capable of entrapping the fluorinated liquids, leading to a system that is both solid-like macroscopically and liquid-like microscopically. Such gels are thermoreversible and can be obtained at gelator concentrations as low as 0.1 wt%, thus, surface tension and capillary action are thought to be the principal forces behind these structures, along with hydrogen-bonding between the gelators molecules, rather than a specific gelator-solvent interaction. This work is the reference for both Chemical Communications, 2005,31: p. 3998-4000 and a manuscript to be submitted.

L'experience de l'imprimeur permet d'eclairer la maniere dont les systemes dissipatifs unidimensionnels peuvent subir une bifurcation secondaire de rupture de parite. Cette these montre que cette bifurcation declenche un mecanisme de readaptation de nombre d'onde dans un systeme de taille finie. Pour caracteriser cette bifurcation, nous avons utilise une methode de perturbation locale qui permet de mesurer un coefficient de diffusion de phase. Un comportement anormal de ce coefficient a ete mis en evidence a proximite du mecanisme de rupture de parite. Nous avons montre dans un modele d'equations d'amplitudes couplees que cette anomalie est la signature de cette bifurcation. Le mecanisme de rupture de parite est ainsi propose comme un mecanisme tres general dans les problemes de selection de nombre d'onde. Pratiquement, la mesure de la diffusion de phase devrait permettre de caracteriser la proximite de la rupture de parite dans d'autres systemes dissipatifs

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2009.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages. 109-121).
Bacteriophage lambda infection of Escherichia coli can result in distinct cell fate outcomes: for example, some cells lyse while others survive as lysogens. A quantitative molecular model of lambda infection supports the hypothesis that spontaneous differences in the timing of individual molecular events during lambda infection leads to variation in the selection of cell fates. Building from this analysis, the lambda lysis-lysogeny decision now serves as a paradigm for how intrinsic biomolecular noise can influence cellular behavior, drive developmental processes, and produce population heterogeneity. The aim of this thesis is to re-evaluate lambda as a paradigm for stochastic behavior by determining whether and to what extent variation in cell fate selection results from pre-existing cell-cell differences rather than chance events during infection. I find that physical differences among cells present prior to infection can control lambda developmental outcomes. Specifically, variation in cell volume at the time of infection can be used to predict cell fate: small cells tend to produce lysogens while larger cells favor lytic growth. I then present evidence that the apparent sensitivity to host volume is encoded by components of the lambda regulatory network acting upstream or at the level of CII, a critical regulator of the lambda lysis-lysogeny decision. I also detail the construction and evaluation of new strains, tools and methodology to size-fractionate populations of cells, to detect lambda infection and gene expression at the single cell level, and to enumerate individual phage particles. My results motivate further research to understand how and to what extent natural biological systems tolerate, buffer or correct for spontaneous molecular variation during development in order to produce deterministic behavior.
by François St-Pierre.
Ph. D.

Brain derived neurotrophic factor is a neurotrophin of vital importance for neuron survival. It may therefore be of great help to people affected by sensorineural hearing loss and cochlear implant users, as it has already been demonstrated that it maintains neuronal cells alive and this proved to be necessary for the device to work. The issue with its clinical application is related to its large size that makes it difficult to deliver. In this thesis I took on one of the tasks of a European project. The objective of the Nanoear project is the creation of multifunctional nanoparticles that could be used as drug carriers for a target delivery in the inner ear. The final aim is to find a substitute for BDNF protein, able to mimic its action but small enough to be attached to the nanoparticles and carry them to their target in the inner ear. The best method to obtain small peptides with these features is the phage display. This technique allows selection of a pool of specific peptides binding specifically to an immobilized target. In collaboration with an English company involved in the project as well, we worked to set all the parameters in order to make the phage display for this project feasible. As our goal was attaining BDNF mimetic peptides our target had to be its functional receptor, TrkB. Starting from a polyA+ RNA library from adult human brain we could get the genes coding for TrkB and BDNF and follow all the process up to the expression of the two proteins in bacteria and in eukaryotic cells, as well. In order to include into nanoparticles the most specific peptides many approaches for the phage display were taken into consideration and experimented on. This technique was in fact performed in vivo on guinea pigs and all the parameters were set for different trials in vitro either on eukaryotic cells or on the specific binding domain purified from bacteria. Therefore the results and the data obtained in this study can lead to a new generation of drug with great clinical potential.

Title: Selection of Local and Expatriate Managers of MNEs in the Post-Entry Phase Authors: Rebecka Nilsson and Tilda Nithenius Level: Master thesis, 30 HP Keywords: Post-Entry Phase, Managerial Selection Strategy, Foreign Activities, Multinational Enterprises, Local Manager, Expatriate Manager     Background: The internationalization of companies contributes to competitive advantage as well as challenges for the companies. In foreign activities enterprises exist in different phases, which might have an impact on the management requirements. This makes the strategy of managerial selection relevant because it will ease the overall foreign activities.     Research Question: Which are the underlying factors that influence the selection of host-country managers in the post-entry phase?   Purpose:The purpose of this study is to develop the understanding for companies’ managerial selection strategies in the post-entry phase. In addition, the purpose of this study is to develop a model that will work as a theoretical guideline for managerial selections.   Theoretical Framework:Theories of firms’ internationalization process, different phases for companies that operate internationally and challenges for companies operating abroad, are presented. Further theories of managerial selection, international human resource management and management of international companies are discussed.     Methodology:This study is made with a qualitative research method and a multiple case-study design, with an abductive approach. Eight Swedish companies operating in China were interviewed through semi-structured and low standardized interviews. The respondents from the companies are top managers operating in China.   Findings:There are three underlying factors; trust, knowledge gap and legitimacy, that influence the managerial selection of host-country managers in the post entry-phase. Each underlying factor is indirect influenced by different factors. The underlying factors are also all influenced by an overall factor, social capital. This study implies that the selection of managers, except top managers, changes in the post-entry phase compared to the entry-phase as they recruit host-country nationals.

Technological advances are required to reduce the environmental impact of the Canadian oil sands. Oxy-direct contact steam generation (DCSG) is one such way to move toward this goal, by producing steam for oil sands operations with a higher efficiency, lower fresh water consumption, and lower CO₂ emissions than traditional once-through steam generators. For DCSG, untreated process water, which may contain a variety of inorganics, is injected directly into the combustor to produce steam. The inorganic material that may deposit in the combustor as a result of that process water was studied for two applications of DCSG in the Canadian oil sands: (1) steam assisted gravity drainage (SAGD), and (2) mining, in order to inform refractory material selection for the combustor. For SAGD, free water knockout tank discharge was used as the process water and resulting deposits in the combustor were predicted to be high in silica and sodium oxide, and enriched with sodium sulfate as the potential operating temperature of the combustor was lowered. At the lowest combustor temperature studied (1075 °C), a low viscosity molten salt phase rich in sodium sulfate was also expected to form. It is recommended that the operating temperature of the combustor be as low as possible while still remaining above the formation temperature of this potentially corrosive salt phase, thus in the range of 1200-1250 °C in the regions of the wall where solids are expected to impact it. A number of candidate refractory materials were assessed through corrosion models and corrosion tests. Aluminosilicate based refractory materials should be avoided due to their potential reaction with the sodium oxide in the slag. This can result in formation of low density solid phases such as nepheline, which can damage the refractory material through volume expansion. Of the three refractories tested, mullite zirconia yielded the worst corrosion resistance, with dissolution of the binder phase and full penetration by sodium oxide. Chromia corundum yielded the greatest resistance to penetration of the materials tested, though some dissolution of the chromia in the slag was still evident. Further investigation into high chrome refractory materials is recommended for this application. For mining applications, mature fine tailings water (MFT) combined with an oil sands processing water (OPW) was used as the process water for injection. Due to the high liquidus of the resulting inorganic deposits, co-injection of a fluxant is recommended to reduce the liquidus and viscosity of the resulting slag solution, thereby maximizing the combustor efficiency by reducing the required operating temperature. Dolomite was identified as the optimal fluxant, at a concentration of 20 wt % CaMgO₂ in the fluxed slag. This mixture was found to have a viscosity of just under 25 Pa·s at 1300 °C, making this a good operating point for the DCSG combustor, as the slag should flow freely and not cause plugging. The corrosion resistance of several candidate refractory materials was assessed through modelling and laboratory scale testing for both the fluxed and non-fluxed slag. Similar to the results for SAGD, of the refractories tested, chromia corundum offered the greatest resistance to penetration, while mullite zirconia was most deeply penetrated by sodium oxide. Again, a chromia-containing refractory is recommended for further investigation for use in the DCSG combustor. Other candidate refractories investigated in the models that warrant testing are chromia spinel and magnesium aluminate spinel. For future work, further corrosion tests at multiple durations are recommended, as well as characterization of refractory samples from CanmetENERGY’s DCSG pilot plant and quantification of the effects of slag exposure on the mechanical strength of the refractory materials.

Zirconium alloys are widely used by the nuclear industry as fuel cladding and structural materials. Many physical and metallurgical properties of zirconium alloys, that are important for their performance in nuclear reactors, are affected by crystallographic texture due to the strong anisotropy of individual crystals. Irradiation assisted growth is one example. Zirconium crystals deform anisotropically under irradiation, which in the presence of strong textures (like the ones observed in cold-rolled sheet) causes undesirable deformation of components during service. For this reason, the nuclear industry is interested in developing thermomechanical processes that produce random textures, taking advantage of the allotropic phase transformation undergone by zirconium, from the low temperature hcp alpha-phase to the high temperature bcc beta-phase. One of these processes is beta-quenching, which has showed certain success in weakening strong rolling textures. However, there is no consensus about the fundamental mechanisms involved.The aim of this work is to study the evolution of the texture of the zirconium alloy Zircaloy-2 during beta-quenching, in order to gain understanding on the mechanisms involved on texture development and evolution during the alpha-to-beta and beta-to-alpha phase transformations. Firstly industrially beta-quenched samples were characterised using well known techniques such as laboratory X-ray diffraction (LXRD) and electron backscatter diffraction (EBSD), which revealed a relationship between peak temperature and the inherited alpha texture. An in situ synchrotron X-ray diffraction (SXRD) experiment provided, for the first time, information of texture evolution of zirconium during rapid changes and at non-ambient conditions. Different peak temperatures and stress/strain conditions were tested. Detailed post mortem EBSD characterisation of samples studied in situ provided insight on the relationship between the microstructure and the texture. Finally, laboratory furnaces were used to beta-quench samples at very high temperature. It was found that there is selection of orientation variants during beta-quenching of zirconium, but while the selection during the alpha-to-beta transformation is almost negligible, depending on the texture evolution of the beta-phase (affected by grain growth and/or plastic deformation), diverse mechanisms of variant selection act during the beta-to-alpha phase transformation. The inherited textures observed result from the combination of these mechanisms. Some of the results of this work can be transferred to other systems such as titanium and the alpha-gamma-alpha phase transformation in steel.

Previous studies on complex chemical systems, approximating enriched ultramafic compositions, have shown that the stability fields of certain phyllosilicate minerals may be shifted through solid solution. This project focuses on three hydrous phases predicted to play an important role in water transfer and storage during subduction. Talc, and at higher pressures the 10 A phase, are expected form in enriched abyssal peridotite within the cold interior of a lithospheric slab, whilst the sodic amphibole eckermannite is expected to be present in the overlying hydrated basalt. Multi-anvil and piston cylinder press experiments in the FeO-MgO-SiO2-H2O (FMSH), NaO-MgO-Al2O3-SiO2-H2O (NMASH), and MgO-Al2O3-SiO2-H2O (MASH) systems have sought to determine the effect of solid solution on the stability on talc and the 10 A phase, with comparison to the end-member MgO-SiO2-H2O (MSH) system. The reaction talc + H2O = 10 A phase has been bracketed in the MSH system at 4.8 GPa/560 ˚C and 5 GPa/640 ˚C, confirming the estimated reaction position from Pawley et al. (2011). Previously unknown values for the entropy and enthalpy of formation of the 10 A phase have been calculated as DeltaHf = -6172.02 kJ and DeltaSf = 320.075 JK-1. At 2 GPa talc containing 0.48 apfu Fe2+ breaks down in the divariant field talc + anthophyllite + quartz + H2O from ~550 ˚C, initiating talc dehydration at temperatures ~270 ˚C lower than in the MSH system. At 4 GPa Fe-bearing talc breaks down in the divariant field talc + enstatite + coesite. A run at 5.2 GPa and 555 ˚C produced 10 A phase containing 0.48 apfu Fe2+. Between 575 ˚C and 600 ˚C at 6.5 GPa phase reversal experiments bracketed the initiation of Fe-bearing 10 A phase dehydration in the divariant field 10 A phase + enstatite + coesite + H2O, corresponding to a reduction in thermal stability of around ~100 ˚C compared to the end-member. The relative positions of the talc and 10 A phase dehydration reactions suggest the latter is able to accommodate greater Fe substitution, and is therefore more stable in the FMSH system. The assemblages 10 A phase + enstatite + coesite + jadeite and 10 A phase + enstatite + pyrope + coesite, were synthesised in the NMASH and MASH systems, respectively. Compositional analysis indicates that the 10 Å phase in these samples contains < 1 weight % Al2O3, with negligible Na. This suggests that Al3+ substitution in talc and the 10 Å phase is unlikely to exert the same stabilising effect observed in a number of other phyllosilicates. Eckermannite was produced in further NMASH experiments at 6.2 GPa. Compositional and structural analysis indicates near-full A-site occupancy and a composition close to that of the end-member, deviating through a minor binary exchange towards Mg-katophorite. This exchange is proposed to stabilise eckermannite to high pressures, beyond previously published limits for sodic amphibole stability. Updated stability fields for talc, the 10 Å phase, and eckermannite were applied to a thermal model for subduction. This predicts that 10 Å phase containing 0.48 apfu Fe2+ may be stable to depths of ~260 km, compared to ~280 km for the end-member. With increasing pressure and temperature Fe-bearing 10 Å phase will dehydrate across a depth range, resulting in either total de-volatilisation, or transfer to other stable high pressure hydrous phases enabling the transport of water to the deeper regions of the mantle.

Cette thèse traite les problèmes statistiques suivants : la sélection de variables dans le modèle de régression linéaire en grande dimension, le clustering dans le modèle de mélange Gaussien, quelques effets de l'adaptabilité sous l'hypothèse de parcimonie ainsi que la simulation des processus Gaussiens.Sous l'hypothèse de parcimonie, la sélection de variables correspond au recouvrement du "petit" ensemble de variables significatives. Nous étudions les propriétés non-asymptotiques de ce problème dans la régression linéaire en grande dimension. De plus, nous caractérisons les conditions optimales nécessaires et suffisantes pour la sélection de variables dans ce modèle. Nous étudions également certains effets de l'adaptation sous la même hypothèse. Dans le modèle à vecteur parcimonieux, nous analysons les changements dans les taux d'estimation de certains des paramètres du modèle lorsque le niveau de bruit ou sa loi nominale sont inconnus.Le clustering est une tâche d'apprentissage statistique non supervisée visant à regrouper des observations proches les unes des autres dans un certain sens. Nous étudions le problème de la détection de communautés dans le modèle de mélange Gaussien à deux composantes, et caractérisons précisément la séparation optimale entre les groupes afin de les recouvrir de façon exacte. Nous fournissons également une procédure en temps polynomial permettant un recouvrement optimal des communautés.Les processus Gaussiens sont extrêmement utiles dans la pratique, par exemple lorsqu'il s'agit de modéliser les fluctuations de prix. Néanmoins, leur simulation n'est pas facile en général. Nous proposons et étudions un nouveau développement en série à taux optimal pour simuler une grande classe de processus Gaussiens
This PhD thesis deals with the following statistical problems: Variable selection in high-Dimensional Linear Regression, Clustering in the Gaussian Mixture Model, Some effects of adaptivity under sparsity and Simulation of Gaussian processes.Under the sparsity assumption, variable selection corresponds to recovering the "small" set of significant variables. We study non-asymptotic properties of this problem in the high-dimensional linear regression. Moreover, we recover optimal necessary and sufficient conditions for variable selection in this model. We also study some effects of adaptation under sparsity. Namely, in the sparse vector model, we investigate, the changes in the estimation rates of some of the model parameters when the noise level or its nominal law are unknown.Clustering is a non-supervised machine learning task aiming to group observations that are close to each other in some sense. We study the problem of community detection in the Gaussian Mixture Model with two components, and characterize precisely the sharp separation between clusters in order to recover exactly the clusters. We also provide a fast polynomial time procedure achieving optimal recovery.Gaussian processes are extremely useful in practice, when it comes to model price fluctuations for instance. Nevertheless, their simulation is not easy in general. We propose and study a new rate-optimal series expansion to simulate a large class of Gaussian processes

Seamless phase II/III clinical trials are attractive in development of new drugs because they accelerate the drug development process. Seamless phase II/III trials are carried out in two stages. After stage 1 (phase II stage), an interim analysis is performed and a decision is made on whether to proceed to stage 2 (phase III stage). If the decision is to continue with further testing, some dose selection procedure is used to determine the set of doses to be tested in stage 2. Methodology exists for the analysis of such trials that allows complete flexibility of the choice of doses that continue to the second stage. There is very little work, however, on optimizing the selection of the doses. This is a challenging problem as it requires incorporation of the dose-response relationship, of the observed safety profile and of the planned analysis method. In this thesis we propose a dose-selection procedure for binary outcomes in adaptive seamless phase II/III clinical trials that incorporates the dose response relationship, and explicitly incorporates both efficacy and toxicity. The choice of the doses to continue to stage 2 is made by comparing the predictive power of the potential sets of doses which might continue to stage 2.