This thesis presents technical and methodological developments aiming tooffer a viable alternative for the treatment of digestive cancers (rectum and esophagus). Compared to the standard methods of therapy, the high intensity contact ultrasound guided by MRI is a less invasive approach. MRI offers 2 advantages: good spatial resolution, and real-time temperature control. This treatment method requires efficacy and safety. Three prototypes of RF coil integrated with ultrasound transducers were built in order to increase the spatial and temporal resolution ofthe MR images, and the accuracy of the temperature measurement. The integrated coils showed a better sensitivity compared to a standard extracorporeal coil. Anatomical (voxel 0.4x0.4x5 mm3)and thermometry (voxel 0.75x0.75x8 mm3, 2s/image) high resolution MR images were acquired in-vivo. The temperature was measured, within a radius of 20 mm from the balloon, with a standard deviation <1°C. The flow artifacts caused by the water circulating inside the cooling balloon could be shifted out of the region of interest. The temperature evolution was controlled automatically, at different depths, with one control point per beam. The controller showed a good accuracy during in-vivo experiments (standard deviation less than 5%). The phased-arrayultra sound transducer permits the successive activation of multiple beams during the same dynamic of sonication. Simulations were conducted in order to offer an optimal treatment planning for a defined tumor. A new design of ultrasound transducer with 256 elements with revolution symmetry, based on a natural geometrical focalization, was proposed.

Le but de la thèse est de modéliser la génération d'ondes élastiques ultrasonores émises par EMATs dans une pièce ferromagnétique, modélisation appliquée au domaine du contrôle non destructif (CND). Les traducteurs EMATs combinent deux physiques différentes : électromagnétisme et élastodynamique. L'enjeu est d'intégrer dans la plateforme de simulation CIVA, dédiée notamment aux CND par courant de Foucault et par ultrasons, les éléments de modélisation inhérents à la problématique multi-physique posée. Ces éléments sont multiples et concernent premièrement la modélisation des forces électromagnétiques créées par un EMAT : la force de Lorentz, existant dans tous milieux conducteurs, et les forces d'aimantation et de magnétostriction, spécifiques aux milieux ferromagnétiques. Deuxièmement, la modélisation proposée prend aussi en compte le phénomène de création d'harmoniques, phénomène dû aux différentes forces et traduisant le fait que les fréquences de l'onde ultrasonore émise peuvent être des harmoniques des fréquences du signal d'excitation de l'EMAT. Le modèle de forces et de création d'harmoniques permet de modéliser des situations de contrôle non prises en compte par les modèles de la littérature, notamment lorsque les champs statiques créés par l'EMAT sont faibles ou lorsque le courant d'excitation possède une forte intensité. Enfin, les forces électromagnétiques sont transformées en contraintes surfaciques équivalentes pour correspondre au formalisme des données d'entrée des modèles de rayonnement des ondes élastiques implémentés dans CIVA. L'outil informatique développé permet donc de traiter toute configuration et condition d'utilisation des EMATs, constituant un outil d'optimisation de leur conception. Les caractéristiques électromagnétiques de différents matériaux, données par l'expérience, sont utilisées pour mener diverses études paramétriques.

Hypoxia is a common feature of solid tumors and one of the hallmarks of tumor microenvironment. Tumor hypoxia plays an important role in angiogenesis, malignant progression, metastatic development, chemo-radio resistance and favours immune evasion by the emergence of tumor variants with increased survival and anti-apoptotic potential. There is very little work done on the impact of tumor hypoxia on the regulation of tumor susceptibility to the lysis induced by cytotoxic antitumor response. Therefore, we asked whether hypoxia confers tumor resistance to cytotoxic T lymphocyte (CTL)-mediated killing. We demonstrated that exposure of target cells to hypoxia has an inhibitory effect on the CTL-mediated autologous target cell lysis. Such inhibition was not associated with an alteration of CTL reactivity and tumor target recognition. We also showed that the concomitant hypoxic induction of Signal transducer and activator of transcription 3 (STAT3) phosphorylation on tyrosine 705 residue (pSTAT3) and hypoxia inducible factor 1 alpha (HIF-1α) is functionally linked to the alteration of Non small cell lung carcinoma (NSCLC) target susceptibility to CTL-mediated killing. We also showed that hypoxia-induced resistance of lung tumor to CTL-mediated lysis was associated with autophagy induction in target cells. Inhibition of autophagy resulted in impairment of pSTAT3 (via inhibition Src kinase) and restoration of hypoxic tumor cell susceptibility to CTL-mediated lysis. Moreover, in vivo inhibition of autophagy by hydroxychloroquine (HCQ) in B16F10 tumor bearing mice and mice vaccinated with TRP2 peptide dramatically increased tumor growth inhibition. Collectively, the current study establishes a novel functional link between hypoxia-induced autophagy and the regulation of antigen specific T cell lysis and points to a major role of autophagy in the control of in vivo tumor growth.Finally, as resistance of tumor targets to killer cells is likely to be regulated by multiple factors, we further aimed to identify the microRNA's regulated by hypoxia in NSCLC and melanoma and their putative involvement in the regulation of tumor susceptibility to antigen-specific CTL-mediated killing. MicroRNA-210 (miR-210) was significantly induced in a HIF-1α dependent manner in NSCLC and melanoma cells and miR-210 was expressed in hypoxic zones of human NSCLC tissues. Moreover, we demonstrated that hypoxia-induced miR-210 regulates tumor cell susceptibility to CTL-mediated lysis in part by suppressing PTPN, HOXA1 and TP53I11 expression indicating that miR-210 plays a potential role in the regulation of anti-tumor immune response.

Within the context of natural language processing, a lemmatiser is one of the most important core technology modules that has to be developed for a particular language. A lemmatiser reduces words in a corpus to the corresponding lemmas of the words in the lexicon. A lemma is defined as the meaningful base form from which other more complex forms (i.e. variants) are derived. Before a lemmatiser can be developed for a specific language, the concept "lemma" as it applies to that specific language should first be defined clearly. This study concludes that, in Setswana, only stems (and not roots) can act independently as words; therefore, only stems should be accepted as lemmas in the context of automatic lemmatisation for Setswana. Five of the seven parts of speech in Setswana could be viewed as closed classes, which means that these classes are not extended by means of regular morphological processes. The two other parts of speech (nouns and verbs) require the implementation of alternation rules to determine the lemma. Such alternation rules were formalised in this study, for the purpose of development of a Setswana lemmatiser. The existing Setswana grammars were used as basis for these rules. Therewith the precision of the formalisation of these existing grammars to lemmatise Setswana words could be determined. The software developed by Van Noord (2002), FSA 6, is one of the best-known applications available for the development of finite state automata and transducers. Regular expressions based on the formalised morphological rules were used in FSA 6 to create finite state transducers. The code subsequently generated by FSA 6 was implemented in the lemmatiser. The metric that applies to the evaluation of the lemmatiser is precision. On a test corpus of 1 000 words, the lemmatiser obtained 70,92%. In another evaluation on 500 complex nouns and 500 complex verbs separately, the lemmatiser obtained 70,96% and 70,52% respectively. Expressed in numbers the precision on 500 complex and simplex nouns was 78,45% and on complex and simplex verbs 79,59%. The quantitative achievement only gives an indication of the relative precision of the grammars. Nevertheless, it did offer analysed data with which the grammars were evaluated qualitatively. The study concludes with an overview of how these results might be improved in the future. / Thesis (M.A. (African Languages))--North-West University, Potchefstroom Campus, 2006.

Die vorliegende Arbeit untersucht, wie die genaue Kenntnis der Sende- und Empfangsschallfelder eines Ultraschallwandlers zur Entwicklung neuer Meßverfahren genutzt werden kann. Insbesondere werden dargestellt: - ein neuartiges, nichtscannendes Verfahren zur Bestimmung der Krümmung eines Reflektors, basierend auf der Analyse der Wellenfrontkrümmung reflektierter Schallfelder - ein neuartiges, nichtinvasives Verfahren zur Bestimmung der Schallgeschwindigkeit in einer Flüssigkeit durch Auswertung der Echosignale von im Ausbreitungsmedium vorhandenen Streupartikeln und - ein Verfahren zur Wandlercharakterisierung durch Messungen in Fluiden mit Streupartikeln, sowie verschiedene Zuordnungen von Schallfeldmerkmalen zu spezifischen Eigenschaften eines Ultraschallwandlers. Im Zusammenspiel von Simulation und Experiment konnten die Funktionstüchtigkeit aller Meßverfahren nachgewiesen und vielversprechende innovative Ansätze für zukünftige Entwicklungen angeregt werden: 1. Das nichtscannende Verfahren zur Krümmungsmessung erlaubt bei guter Justage eine Krümmungsbestimmung von Reflektoren mit Radien zwischen 6 und 11 mm mit einer Unsicherheit von ungefähr 0,5 mm. In Kombination mit herkömmlichen scannenden Verfahren bietet es Ansätze zur präzisen Größenbestimmung von Fehlern in der zerstörungsfreien Prüfung. 2. Das Verfahren zur nichtinvasiven Schallgeschwindigkeitsmessung erlaubt eine Bestimmung von Schallgeschwindigkeiten mit einer statistischen Meßunsicherheit von 0,1 %. Mögliche Weiterentwicklungen zur Messung der Schallgeschwindigkeit mit örtlicher Auflösung und zur Gewinnung neuer Diagnosemöglichkeiten in Metallurgie (nichtinvasive Charakterisierung von Mischungsvorgängen) und Biomedizintechnik (nichtinvasive Temperaturmessung in Körpergewebe zur Überwachung der Hyperthermiebehandlung, Gewebecharakterisierung) werden erläutert. Aus verschiedenen bekannten sowie einem neuartigen, leicht anwendbaren Meßverfahren werden neue Schlüsse gezogen a) zur Bestimmung der akustisch effektiven Elementgröße von Wandlerelementen mittels Schallfeldmessungen, b) zur Qualitätssicherung im Hinblick auf Schallkopfasymmetrien und c) zur Verbesserung von Schallfeldsimulationen. / The current thesis explores how the precise knowledge of the sending and receiving sound fields of an ultrasonic transducer can contribute to the development of novel measuring techniques. Emphasis is placed on: - a novel, non-scanning method for the determination of the curvature radius of a spherical reflector, based on the analysis of the wave front curvature of the reflected sound field, - a novel non-invasive method for sound velocity measurements in fluids using the echo signals from scattering particles, and - novel conclusions on how to use well-known sound field measurement methods for transducer characterisation, as well as an introduction to a novel easy-to-use method for transducer characterisation exploiting the echo signals from scattering particles. Proof of concept is shown for all methods by simulation and measurement, and different promising improvements for further techniques are suggested: - The non-scanning method for curvature measurements makes it possible to determine reflector radii between 6 and 11 mm with an uncertainty of about 0.5 mm, provided that there is a good reflector alignment. In combination with conventional methods, a novel approach for the determination of the size of discontinuities in non-destructive testing is outlined. - The method for non-invasive sound velocity measurements allows the determination of sound velocity in homogeneous fluids with a statistical uncertainty of 0.1 %. Future improvements are suggested to allow sound velocity measurements with local resolution, which enables novel approaches for metallurgy (non-invasive characterisation of mixing processes) and biomedical engineering (non-invasive temperature control for hyperthermia treatment, tissue characterisation). - New conclusions are drawn based on well-established and a novel easy-to-implement measurement method regarding a) the determination of the acoustically effective element size of transducer elements, b) transducer asymmetries, thereby improving quality control, and c) the improvement of sound field simulations.

Microelectromechanical resonators have found widespread applications in timing, sensing and spectral processing. One of the important performance metrics of MEMS resonators is the temperature sensitivity of their frequency. The main objective of this dissertation is the compensation and control of the temperature sensitivity of silicon resonators through engineering of device geometry and structural composition. This has been accomplished through formation of composite platforms or novel geometries based on dispersion characteristics of guided acoustic waves in single crystalline silicon (SCS) microstructures. Furthermore, another objective of this dissertation is to develop efficient longitudinal piezoelectric transduction for in-plane resonance modes of SCS resonators that have lithographically-defined frequencies, to reduce their motional resistance (Rm). A uniformly distributed matrix of silicon dioxide pillars is embedded inside the silicon substrate to form a homogenous composite silicon-oxide platform (SilOx) with nearly perfect temperature-compensated stiffness moduli. Temperature-stable micro-resonators implemented in SilOx platform operating in any desired in- and out-of-plane resonance modes show full compensation of linear temperature coefficient of frequency (TCF). Overall frequency drifts as small as 80 ppm has been achieved over the industrial temperature range (-40°C to 80°C) showing a 40x improvement compared to uncompensated native silicon resonators. A 27 MHz temperature-compensated MEMS oscillator implemented using SilOx resonator demonstrated sub-ppm instability over the industrial temperature range. Besides this, a new formulation of different resonance modes of SCS resonators based on their constituent acoustic waves is presented in this dissertation. This enables engineering of the acoustic resonator to provide several resonance modes with mechanical energy trapped in central part of the resonator, thus obviating narrow tethers traditionally used for anchoring the cavity to the substrate. This facilitates simultaneous piezoelectric-transduction of multiple modes with different TCFs through independent electrical ports, which can realize highly accurate self-temperature sensing of the device using a beat frequency (fb) generated from linear combination of different modes. Piezoelectrically-transduced multi-port silicon resonators implemented using this technique provide highly temperature-sensitive fb with a large TCF of ~8500 ppm/°C showing 100x improvement compared to other Quartz/MEMS counterparts, suggesting these devices as highly sensitive temperature sensors for environmental sensing and temperature-compensated/oven-controlled crystal oscillator (TCXO/OCXO) applications. Another part of this dissertation introduces a novel longitudinal piezoelectric transduction technique developed for implementation of low Rm silicon resonators operating in lithographically defined in-plane modes. Aluminum nitride films deposited on the sidewalls of thick silicon microstructures provides efficient electromechanical transduction required to achieve low Rm. 100 MHz SCS bulk acoustic resonators implemented using this transduction technique demonstrates Rm of 33Ω showing a 100x improvement compared to electrostatically transduced counterparts. Low-loss narrow-band filters with tunable bandwidth and frequency have been implemented by electrical coupling of these devices, showing their potential for realization of truly reconfigurable and programmable filter arrays required for software-defined radios.

Les réseaux de nanotrous sont des structures plasmoniques ayant un énorme potentiel en tant que transducteurs pour la conception de biocapteurs. De telles structures sont prometteuses pour l’élaboration de biocapteurs capable d’effectuer du criblage à haut débit. L’intérêt de travailler avec des réseaux de nanotrous est dû à la simplicité d’excitation des polaritons de plasmons de surface en transmission directe, à la sensibilité et à la facilité de fabrication de ces senseurs. L’architecture de tels réseaux métalliques permet la conception de nanostructures ayant de multiples propriétés plasmoniques. L’intensité, la signature spectrale et la sensibilité du signal plasmonique sont grandement affectées par l’aspect physique du réseau de nanotrous. L’optimisation du signal plasmonique nécessite ainsi un ajustement du diamètre des trous, de la périodicité et de la composition métallique du réseau. L'agencement de l'ensemble de ces paramètres permet d'identifier une structure optimale possédant une périodicité de 1000 nm, un diamètre des nanotrous de 600-650 nm et un film métallique ayant une épaisseur de 125 nm d'or. Ce type de transducteur a une sensibilité en solution de 500-600 nm/RIU pour des bandes plasmoniques situées entre 600-700 nm. L'intérêt de travailler avec cette structure est la possibilité d'exciter les plasmons de polaritons de surface (SPPs) selon deux modes d'excitation : en transmission exaltée (EOT) ou en réflexion totale interne par résonance des plasmons de surface (SPR). Une comparaison entre les propriétés plasmoniques des senseurs selon les modes d'excitation permet de déterminer expérimentalement que le couplage de la lumière avec les ondes de SPP de Bloch (BW-SPPs) en transmission directe résulte en un champ électromagnétique davantage propagatif que localisé. D'un point de vue analytique, la biodétection de l'IgG en SPR est 6 fois plus sensible par rapport au mode EOT pour une même structure. Une étude du signal plasmonique associé au BW-SPP pour un certain mode de diffraction démontre que la distance de pénétration de ces structures en EOT est d'environ 140 nm. La limite de détection de l'IgG humain pour un réseau de nanotrous de 1000 nm de périodicité est d'environ 50 nM en EOT. Ce mémoire démontre la viabilité des réseaux de nanotrous pour effectuer de la biodétection par criblage à haut débit lors de prochaines recherches. L'investigation de l'effet de l'angle d'excitation en transmission exaltée par rapport au signal plasmonique associé au mode (1,0) d'un réseau de nanotrous de 820 nm d'or démontre que la sensibilité en solution n'est pas proportionnelle à la sensibilité en surface du senseur. En fait, une optimisation de l'angle d'incidence pour le mode (1,0) de diffraction des BW-SPP permet d'amplifier la sensibilité en surface du senseur jusqu'à 3-fois pour un angle de 13,3°. Ce mémoire démontre ainsi la nécessité d'optimiser l'angle d'excitation et les propriétés physiques du senseur afin de développer un transducteur de grande sensibilité basé sur l'excitation en transmission de réseaux de nanotrous. / This research aims at developing a multiplexed biosensor for protein detection based on the nanohole array technology. Gold nanohole arrays exhibit distinct plasmonics properties depending on the excitation mode of the surface plasmon polaritons (SPPs). The interest of working with nanohole arrays is related to their high sensitivity, ease of fabrication and simple setup of excitation in transmission. The architecture of nanohole arrays leads to a nanostructure having multiple plasmonics properties. The intensity, the spectral signature and the sensitivity of the plasmonic signal were highly affected by the shape of the nanohole arrays. Varying the diameter of the holes, the periodicity and the metallic composition of the array were used to optimize the plasmonic signal. The optimal structure was found to have a periodicity of 1000 nm, a diameter of 600-650 nm and a metallic film with a thickness of 125 nm of gold. Such a transducer exhibits a bulk refractive index sensitivity of 500-600 nm/RIU for plasmonic bands absorbing around 600-700 nm. Surface plasmon resonance (SPR) in the Kretschmann configuration and enhanced optical transmission (EOT) mode were compared using large gold nanohole arrays (1000 nm periodicity, 600 nm diameter and 125 nm depth) in order to assess their relative analytical performance. Biodetection of IgG was found to be 6 times more sensitive with SPR in the Kretschmann configuration than in EOT mode for the same structure. The decay length of the electromagnetic field in EOT mode was determined experimentally to be around 140 nm with a layer-by-layer polyelectrolyte deposition. This results suggests that the plasmonic properties of EOT for nanohole arrays is much more associated to a Bloch wave SPPs mode rather than a localized SPR. Variation of the incident angle of excitation of the BW-SPPs in transmission leads to a higher surface sensitivity for the (1,0) diffraction mode for gold nanohole arrays of 820 nm periodicity. Optimization of the physical properties and the excitation angle of the nanohole arrays is essential in order to develop a transducer having a potential towards multiplexed biosensors.

Virtual three-dimensional auditory displays (V3DADs) use digital signal processing to deliver sounds (typically through headphones) that seem to originate from specific external spatial locations. This set of studies investigates the delivery of V3DADs through bone-conduction transducers (BCTs) in addition to conventional headphones. Although previous research has shown that spatial separation can be induced through BCTs, some additional signal adjustments are required for optimization of V3DADs, due to the difference in hearing pathways. The present studies tested a bone-conduction adjustment function (BAF) derived from equal-loudness judgments on pure tones whose frequencies were spaced one critical band apart. Localization performance was assessed through conventional air-conduction headphones, BCTs with only transducer correction, and BCTs with a BAF. The results showed that in the elevation plane, the BAF was effective in restoring the spectral cues altered by the bone-conduction pathway. No evidence for increased percept variability or decreased lateralization in the bone-conduction conditions was found. These findings indicate that a V3DAD can be implemented on a BCT and that a BAF will improve performance, but that there is an apparent performance cost that cannot be addressed with BAFs measured using the methodology in the present studies.

The recent development of the commercially viable thin film electro-acoustic technology has triggered a growing interest in the research of plate guided wave or Lamb wave components owing to their unique characteristics. In the present thesis i) an experimental study of the thin film plate resonators (FPAR) performance operating on the lowest symmetrical Lamb wave (S0) propagating in highly textured AlN membranes versus a variety of design parameters has been performed. The S0 mode is excited through an Interdigital Transducer and confined within the structure by means of reflection from metal strip gratings. Devices operating in the vicinity of the stop-band center exhibiting a Q-value of up to 3000 at a frequency around 900MHz have been demonstrated. Temperature compensation of this type of devices has been studied theoretically and successfully realized experimentally for the first time. Further, integrated circuit-compatible S0 Lamb based two-port FPAR stabilized oscillators exhibiting phase noise of -92 dBc/Hz at 1 kHz frequency offset with feasible thermal noise floor below -180 dBc/Hz have been tested under high power for a couple of weeks. More specifically, the FPARs under test have been running without any performance degradation at up to 27 dBm loop power. Further, the S0 mode was experimentally demonstrated to be highly mass and pressure sensitive as well as suitable for in-liquid operation, which together with low phase noise and high Q makes it very suitable for sensor applications; ii) research in view of FPARs operating on other types of Lamb waves as well as novel operation principles has been initiated. In this work, first results on the design, fabrication and characterization of two novel type resonators: The Zero Group Velocity Resonators (ZGVR) and The Intermode-Coupled Thin Film Plate Acoustic Resonators (IC-FPAR), exploiting new principles of operation have been successfully demonstrated. The former exploits the intrinsic zero group velocity feature of the S1 Lamb mode for certain combination of design parameters while the latter takes advantage of the intermode interaction (involving scattering) between S0 and A1 Lamb modes through specially designed metal strip gratings (couplers). Thus both type of resonators operate on principles of confining energy under IDT other than reflection.

Orientador: Jozue Vieira Filho / Resumo: Neste trabalho foram realizados estudos, análises, simulações e implementações de um sistema de power harvesting utilizando transdutores piezelétricos, com o objetivo de extrair a máxima potência. A fim de alcançar tal objetivo, o sistema mecânico e a interface elétrica foram analisados com foco na quantidade de potência extraída. Com os resultados básicos desses estudos, tem-se que o desempenho de tais sistemas depende da interação eletromecânica, da deformação, da frequência de excitação e da carga conectada. Com exceção do último, esses parâmetros não interferem no modelo tradicional de simulação no SPICE. Para aprimorar os resultados da simulação, foi proposta uma metodologia para a modelagem do sistema mecânico com a interface elétrica, implementada e avaliada em MATLAB/Simulink e em SPICE com VHDL-AMS. Além disso, um novo circuito eletrônico, denominado Conversor Direto CA-CC com Chaveamento Sincronizado - CDCS, foi projetado para maximizar a potência média extraída e reduzir sua dependência com a frequência de excitação e com a carga conectada. Os resultados das simulações foram comparados com dados experimentais para os circuitos eletrônicos retificador em ponte e SSHI em paralelo. A modelagem desenvolvida em SPICE com VHDL-AMS apresentou melhores resultados, pois permite uma modelagem mais precisa dos componentes eletrônicos sem comprometer o domínio mecânico. Comparado com três circuitos existentes na literatura (retificador em ponte, SSHI em paralelo e SECE), o cir... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: In this work studies, analysis, simulations and the implementation of power harvesting system using piezoelectric transducer were done aiming to extract its maximum power. In order to achieve this goal, the mechanical system and electrical interface were analyzed especially focused on the amount of power that can be able to extracted. The conclusion of these studies was that the system performance depends of the electromechanical interaction, deformation, excitation frequency and the connected load. Except for the latter, these parameters does not interfered in the standard model by SPICE. To improve the simulation results, a novel methodology for modeling the mechanical system with electrical interface was proposed. It was implemented and evaluated in MATLAB/Simulink and in SPICE with VHDL-AMS. In addition, a new electronic circuit, well know as Direct AC-DC Converter with Synchronous Switch (CDSS), was designed to improve the extract power and the response at the frequency of excitation and the connected load. The simulation results were compared with experimental data for the electronic circuits: bridge rectifier and P-SSHI. The SPICE with VHDL-AMS model offered the best results, since it allows accurate model for the electrical component without compromising the mechanical system. The performance of the proposed circuit was compared with three electronic circuits (bridge rectifier, P-SSHI and SECE). The results show that the proposed circuit presented the higher power ext... (Complete abstract click electronic access below) / Doutor