Дисертації з теми "Ablation mechanism"

Pulsed Plasma Thrusters (PPTs) are long standing electric propulsion thrusters that are reliable, relatively simple and low cost. One of the main issues with the PPT is its poor utilization of the propellant and low efficiency. Typically only 40-60% of the propellant contributes to the production significant impulse and the efficiency is around 8%. The cause of the PPT’s poor propellant utilization is the late time ablation (LTA), which has a major impact on the efficiency. LTA is the sublimation of propellant that takes place after the main discharge, due to the propellant, usually Polytetrafluoroethylene (Teflon®), being at a temperature above its sublimation point. The LTA produces a low speed gas and macro particles that do not contribute significantly to the thrust. This work presents a way of accelerating the late time ablation by employing an additional discharge after the main discharge, in a separate pair of electrodes. A new thruster, called the two-stage pulsed plasma thruster (TS-PPT) was built and tested. This thruster has two pair of electrodes: primary and secondary. The primary is placed in contact with the propellant surface, as in a regular PPT. The secondary is placed downstream, relatively far from the propellant. A new approach, dividing the PPT thrust generation in two phases, was envisioned. The first phase is responsible for the ablation process and takes place in the first pair of electrodes. The second phase takes place in the second pair of electrodes and is responsible for the acceleration process. The phase division allowed for propellant metering and better propellant utilization. Evidence was found that a pair of electrodes placed downstream, further from the propellant surface is able to discharge in the late ablation portion of the propellant and can impart extra energy into the exhaust and improve propellant utilization. A simple analytical model was developed to predict trends. A prototype of a TS-PPT was designed and built. A vacuum facility was modified, adapted, partially designed and built. An average mass bit consumption test was carried out. A simple time-of-flight experiment revealed that the fastest portions of the plasma from the primary electrodes discharge were travelling at around 33 km/s. Several current measurements were performed and calculations of the total electrical resistance, total inductance, electromagnetic impulse bit, specific impulse, efficiency, and other parameters were calculated based on experimental data. Experimental results indicated that significant improvements in the specific impulse and efficiency are possible by utilising a two-stage PPT. Specific impulses as high as 4000s were calculated based on experimental results, indicating a better propellant utilization.

Abstract Nd-modified lead-zirconate-titanate (PNZT) thin films were deposited on MgO(100), Si(100) and Al2O3(1102) single-crystal substrates using the pulsed-laser-ablation technique with a XeCl excimer laser. The post-annealing heat-treatment technique was used for the crystallisation of the films. The structural characterization, microstructure and the chemical composition of the thin films and of the ceramic Pb0.97Nd0.02(Zr0.55Ti0.45)O3 targets after ablation were studied using x-ray diffraction, scanning electron microscopy and energy-dispersive x-ray spectroscopy, respectively. The formation of the particulates on the target surface during the ablation process and the effect of the particulates on the quality of the thin films were studied. Typically, the ferroelectric PNZT thin films for the capacitor structures were deposited at the laser-beam fluence of around 1.0 J/cm2 and annealed at the temperatures from 600 to 700 °C. The dielectric and, especially, the polarization properties and the residual macroscopic stress state of the PNZT thin films were studied. The relationship between the electrical properties of the films and the nature of the stress state was also investigated. The average growth rate of the PNZT films increased linearly with increasing laser-beam fluence above the threshold value of around 0.4 J/cm2. The composition of the PNZT films varied strongly with the deposition laser-beam fluence and annealing temperature. The phase structure of PNZT films ablated from Pb0.97Nd0.02(Zr0.55Ti0.45)O3 targets could be adjusted between tetragonal and rhombohedral structures by changing the incident laser-beam fluence on the target surface. The surface of the target after ablation was covered by the laser-cone structure and the topmost layer of the target was amorphous having TiO2 and ZrO2 structures with separate segregated lead droplets. On MgO substrates, values of the relative dielectric constant er from 430 to 560 and of the remanent polarization εr of the order of 18 μC/cm2 were achieved in PNZT films which were under a compressive stress of the order of 300 MPa. On silicon substrates, εr was around 100 and the polarization properties of the films were modest due to a strong tensile stress of the order of 400 MPa. The Poole-Frenkel conduction mechanism with the activation energy of around 0.2 eV was found responsible for the leakage conductivity in the capacitor structures with PNZT films.

Prolonged periods of non-weightbearing activity result in a significant loss of bone mass which increases the risk of fracture with the initiation of mechanical loading. The loss of bone mass is partially driven by declines in bone formation yet the mechanisms responsible for this decline are unclear. To investigate the limitations of osteoblasts during disuse, marrow ablation was superimposed on hindlimb unloaded mice. Marrow ablation is a useful model to study osteoblast functionality as new cancellous bone is rapidly formed throughout the marrow of a long bone while hindlimb unloading is the most common method used to produce skeletal unloading. The specific hypotheses of this study were aimed at determining if changes in osteoblast functionality, differentiation, and/or proliferation were compromised in non-weightbearing bone in response to a bone formation stimulus. Additionally, the influence of having compromised osteoblast functionality at the time of stimulation was assessed in non-weightbearing bones. Key outcome measures used to address these hypotheses included static and dynamic cancellous bone histomorphometry, bone densitometry, and real-time polymerase chain reaction (PCR) analyses of gene expression. The results document similar ablation-induced increases of cancellous bone in both weightbearing and unloaded animals. Similarly, there was no influence of load on ablation-induced increases in cancellous bone forming surface or mineral apposition rate. Unloading did significantly attenuate the ablation-induced increase in bone formation rate, due to reduced levels of total surface mineralization. When osteoblast functionality was compromised prior to marrow ablation, bone formation rate increases were also attenuated in ablated animals due to reduced mineralization. Additionally, increases in forming surface were attenuated as compared to unloaded animals having normal osteoblast function at the time of ablation. Collectively, these data identify mineralization as the limiting step in new bone formation during periods of disuse. The caveat, however, is that when bone formation is stimulated after a period of unloading sufficient to compromise osteoblast functionality, increases in osteoblast recruitment to the bone surface are compromised.

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Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Pour ce travail de thèse, le dépôt électrochimique de Ni/Cu est étudié en tant qu’alternative à la sérigraphie à base de pates d’Ag et Al pour métalliser les cellules solaires en silicium cristallin. Cette technique a le potentiel d’améliorer la qualité des contacts métalliques et d’augmenter l’efficacité des cellules solaires en silicium. Les métaux utilisés étant moins coûteux, une diminution des coûts de production est envisageable. Cependant, le dépôt Ni/Cu doit être amélioré pour une application industrielle dans le domaine photovoltaïque.L’objectif de cette thèse est d’étudier les différentes étapes du procédé de dépôt de Ni/Cu sur des cellules solaires n-PERT bifaciales afin de comprendre les mécanismes physicochimiques impliqués et résoudre les différents verrous relatifs à cette technique.La première étape, qui consiste à ouvrir selectivement les couches dielectriques par ablation laser, a été optimisée en choisissant des paramètres limitant l’endommagement du silicium sous-jacent. Un mécanisme d’ablation a également été proposé. La désoxydation et l’activation au palladium du silicium, ont été étudiés dans deux milieux fluorés (HF et NaHF2). De meilleurs résultats en terme de gravure du SiOx et d’activation ont été obtenus avec NaHF2. L’inhomogénité du dépôt de nickel a soulignée l’importance de réaliser ce dépôt dans l’obscurité. Une mauvaise adhérence sur surface polie a été observée et des axes d’amélioration ont été proposés. L’impact de paramètres de recuit non adaptés sur le rendement des cellules a été étudié. Un procédé de plating Ni/Cu optimisé a été developpé et des rendements similaires aux références sérigraphiées ont été obtenus
In this thesis work, Ni/Cu electrochemical deposition (“plating”) is studied as an alternative to the mainstream screen-printing technique based on Ag and Al metallic pastes to produce industrial c-Si solar cells. Ni/Cu plating has the potential to improve the quality of metallic contacts and increase c-Si solar cell efficiency. The use of cheaper metals is a strong asset to reduce the production costs. However, Ni/Cu plating is still at an introductory phase and there are some issues to deal with.The goal of this thesis is to investigate the successive steps of Ni/Cu plating process for bifacial n-PERT c-Si solar cells and understand the physico-chemical phenomena involved to address the related issues.On the first step, laser ablation parameters have been optimized to selectively ablate the dielectric layers while limiting the impact on the underlying Si. An ablation mechanism has also been proposed. Next steps of deoxidation and Pd activation of Si surface have been studied in two fluoride media (HF and NaHF2). NaHF2 provided higher SiOx etching rates and better Si surface activation. Next, homogeneity issues of Ni electroless deposition have been found, highlighting the need to make the deposition in dark conditions. Poor adherence on polished surface has been observed and areas of improvement have been suggested. The impact of non-optimized annealing parameters on cells conversion efficiencies has been demonstrated. The Ni/Cu plating process has been improved similar efficiencies than those of screen-printed reference cells have been achieved

Le besoin d'une très grande précision lors du traitement des matériaux par laser a fortement encouragé le développement des études de l'effet des impulsions ultra brèves pour la structuration des matériaux à une échelle micro et nano métrique. Une diffusion d'énergie minimale et une forte non linéarité de l'interaction permet un important confinement énergétique à des échelles les plus petites possibles. La possibilité d'introduire des changements de phases rapides et même de créer de nouveaux états de matière ayant des propriétés optimisées et des fonctions améliorées donne aux impulsions ultra brèves de sérieux arguments pour être utilisées dans des dispositifs très précis de transformation et de structuration des matériaux. L'étude de ces mécanismes de structuration et, en particulier, de leurs caractéristiques dynamiques, est une clé pour l'optimisation de l'interaction laser-matière suivant de nombreux critères utiles pour les procédés laser : efficacité, précision, qualité. Ce mémoire synthétise les travaux de l'auteur sur l'étude statique et dynamique du dépôt d'énergie ultra rapide, avec application aux procédés laser. La connaissance de la réponse dynamique des matériaux après irradiation laser ultra brève montre que les temps de relaxation pilotent l'interaction lumière-matière. Il est alors possible d'adapter l'énergie déposée à la réponse du matériau en utilisant les toutes récentes techniques de mise en forme spatio temporelle de faisceaux. Un couplage optimal de l'énergie donne la possibilité d'orienter la réponse du matériau vers un résultat recherché, offrant une grande flexibilité de contrôle des procédés et, sans doute, la première étape du développement de procédés « intelligents ».

Meiosis is a fundamental part in the life cycle of sexual species. It denotes a specialised cell division that halves chromosome numbers to generate haploid gametes for reproduction. Cells unable to competently progress through meiotic prophase activate cell surveillance mechanisms causing their elimination. Given the importance of DNA damage kinases like ATR in facilitating mitotic cell surveillance mechanisms, I characterized Atr-deficient spermatocytes to determine the importance of ATR for mammalian meiosis. I found that ATR ensures efficient chromosome synapsis, and that that is partially independent of meiotic recombination. In addition, ATR has three distinct roles in meiotic recombination. Firstly, during nucleolytic processing, it acts to regulate SPO11-oligonucleotide size when ATM is deleted. Secondly, it is required for accurate RAD51 and DMC1 recruitment to DSBs. Thirdly, it regulates the timing of DNA DSB repair on both unsynapsed and synapsed chromosomes. Finally I found that the loss of ATR is unable to rescue meiotic arrest in multiple meiotic mutants, including mice deficient for the other DNA damage PIKKs ATM and DNA-PK. My findings reveal multiple roles for ATR in male mouse meiosis.

Electroporation is a biophysical phenomenon in which cell membrane permeability to ions and molecules is increased when the cell is briefly exposed to high electric fields. Electroporation is the basis of multiple novel clinical treatment modalities. Reversible electroporation is the basis of Electrochemotherapy (ECT), a cancer treatment modality in which electric pulses are applied to enhance cellular uptake of chemotherapeutic agents. It is also the basis of Gene Electrotransfer, which is used in multiple therapies under clinical trials, including cancer treatments and vaccination. Irreversible electroporation (IRE) is used as a non-thermal ablation technique for treatment of solid tumors. Electrolytic Electroporation (E2) is a novel tissue ablation technique which combines reversible electroporation with electrolysis. This research project aimed at better understanding the interplay of the two components of E2 to achieve tumor eradication. In order to investigate the cell killing mechanism, in vitro, in vivo and in silico studies were performed and the information obtained was combined to demonstrate the E2’s underlying mechanisms of action.
La electroporación es un fenómeno biofísico por el cual se aumenta la permeabilidad de la membrana celular a iones y moléculas cuando la célula se expone brevemente a elevados campos eléctricos. La electroporación es la base de múltiples modalidades novedosas de tratamiento clínico. La electroporación reversible es la base de la electroquimioterapia (ECT por sus siglas en inglés), una modalidad de tratamiento del cáncer en la que se aplican impulsos eléctricos para mejorar la absorción celular de agentes quimioterapéuticos. También es la base de la electrotransferencia génica, que se utiliza en múltiples terapias en pruebas clínicas, entre ellas vacunas y tratamientos contra el cáncer. La electroporación irreversible (IRE por sus siglas en inglés) se utiliza como técnica de ablación no térmica para el tratamiento de tumores sólidos. La electroporación electrolítica (E2) es una novedosa técnica de ablación de tejidos que combina la electroporación reversible con la electrólisis. El objetivo de este proyecto de investigación fue conocer mejor la interacción entre los dos componentes de la E2 para lograr la erradicación de los tumores. Para investigar el mecanismo de destrucción de células, se llevaron a cabo estudios in vitro, in vivo e in silico, y la información obtenida se combinó para demostrar los mecanismos de actuación subyacentes de la E2.

Les matériaux ferroélectriques suscitent beaucoup d’intérêt du fait de leurs propriétés physiques telles que la piézoélectricité, la ferroélectricité ou encore leur permittivité élevée. Ainsi, on cherche à les intégrer dans les micro- et nano-systèmes dans lesquels on les retrouve généralement sous forme de couche mince dans une configuration de type capacité plane. En particulier, l’oxyde de plomb, titane et zirconium (PZT) est un matériau très attractif pour les applications RF capacitives du fait de sa grande permittivité. Son intégration sur des électrodes métalliques, i.e. les lignes coplanaires constituant le guide d’onde, implique de maîtriser sa croissance en film mince. L’application d’une tension dans un dispositif RF actif impose également de contrôler les propriétés électriques : nature des courants de fuite et comportement ferroélectrique du PZT. Dans ce contexte, les couches minces de PZT sont déposées par ablation laser (PLD) sur un empilement La₀.₆₇Sr₀.₃₃MnO₃ (LSMO) / Pt (111) déposé sur un substrat monocristallin de saphir. La couche d’accroche conductrice LSMO est nécessaire afin d’éviter la formation d’une phase pyrochlore paraélectrique. Le contrôle de l’orientation cristalline de la couche de LSMO permet de contrôler la texturation de la couche de PZT. Les courants de fuite au travers de l’empilement Pt/PZT/LSMO/Pt ont ensuite été étudiés dans l’intervalle de température 220-330K de façon à déterminer les mécanismes de conduction. Une transition a été mise en évidence entre, autour de la température ambiante, un mécanisme contrôlé par la diffusion des charges en volume et, à basse température, un mécanisme contrôlé par l’injection des charges aux interfaces électrode/PZT. Un mécanisme par sauts a été identifié au-dessus de 280K en cohérence avec la présence de défauts étendus et la structure colonnaire du PZT. Afin de contrôler ces courants de fuite, différentes stratégies ont été utilisées. La première consiste à insérer une couche d’oxyde isolante à l’interface supérieure Pt/PZT modifiant ainsi l’injection des charges et permettant de réduire les courants de fuite. La seconde stratégie consiste, quant à elle, à modifier la structure de la couche de PZT en volume en élaborant des composites diélectrique/PZT multicouches ou colonnaires. Ainsi, une couche d’oxyde isolante a été insérée au milieu de la couche de PZT et a permis de réduire les courants de fuite. Le contrôle de la nucléation du PZT a également permis par nanofabrication d’élaborer un composite colonnaire pérovskite PZT/pyrochlore. La densité de piliers de pyrochlore dans la phase ferroélectrique permet de moduler la densité de courant dans la structure. Le PZT et les hétérostructures permettant de réduire les courants de fuite ont ensuite été intégrés dans une structure RF capacitive avec des lignes coplanaires d’or. Les performances RF en termes d’isolation et de pertes par insertion ainsi que la compatibilité de ces différents matériaux ont été étudiées et ont montré que les solutions développées dans le cadre du contrôle des courants de fuite sont prometteuses pour être intégrées dans les dispositifs RF capacitifs. En outre, on a cherché à extraire la permittivité à haute fréquence du PZT lorsque celui-ci est inséré dans une structure capacitive. Cette étude a notamment permis de mettre en évidence les points techniques à modifier concernant la structure du dispositif afin de parvenir à exploiter les propriétés physiques du PZT à haute fréquence
Ferroelectric materials are raising a lot of interest due to their physical properties such as piezoelectricity, ferroelectricity or high dielectric constant. Thus, they are generally integrated in micro- and nano-systems as thin films in a capacitive configuration. Especially, the lead zirconate titanate oxide (PZT) is an attractive material for capacitive RF applications due to its high dielectric constant. The growth of the PZT thin film has to be controlled on metallic electrodes for its integration on coplanar transmission lines. Moreover, electrical properties such as leakage current and ferroelectric behavior of PZT have to be monitored upon application of a dc voltage bias for RF device operation. In this context, PZT thin films were grown by the pulsed laser deposition technique (PLD) on a La₀.₆₇Sr₀.₃₃MnO₃ (LSMO) / Pt (111) electrode on a monocrystalline sapphire substrate. The LSMO buffer layer is mandatory to avoid the formation of the paraelectric pyrochlore phase. The control of the crystalline orientation of the LSMO layer allows for the control of the PZT layer texture. Leakage currents through the Pt/PZT/LSMO/Pt stack were then studied in the 220-330K temperature range to determine the conduction mechanisms. A transition is evidenced between a bulk-controlled mechanism near room temperature and an interface-controlled mechanism at low temperature. A hopping mechanism is identified above 280K in line with the presence of extended defects and the columnar structure of the PZT layer. Several strategies were tested to control leakage currents. The first one consists in inserting an insulating oxide layer at the top Pt/PZT interface. In this way, charge injection was modified and leakage currents were reduced. The second strategy consists in changing the PZT layer bulk structure by elaborating a layered or columnar dielectric/PZT composite. Thus, an insulating oxide layer was inserted in the middle of the PZT layer and permitted to reduce leakage currents. Moreover, the control of the PZT nucleation allowed for the elaboration of a columnar PZT/pyrochlore composite. The leakage currents in this composite can be tuned through the pyrochlore pillars density among the ferroelectric matrix. Then, PZT and the heterostructures for leakage current control were integrated in a capacitive RF structure with gold coplanar transmission lines. RF performances in terms of isolation and insertion loss of these materials were studied and gave good results. In particular the heterostructures developed to control the leakage currents are promising for their integration in capacitive RF devices. Besides, I tried to extract the permittivity of PZT at high frequency with the PZT layer in a capacitive configuration. This study highlighted the essential modifications of the capacitive structure that have to be made in order to be able to exploit PZT properties at high frequency

Die Synthese kolloidaler Nanopartikel ist daher eines der wichtigsten Forschungsthemen der letzten Jahre. Die gepulste Laserablation in Flüssigkeiten stellt eine Alternative zu den nasschemischen Synthesewegen dar. Merkmale der gepulsten Laserablation in Flüssigkeiten ist der geringe experimentelle Aufwand, die Vielseitigkeit und die Möglichkeit stabilisatorfreie kolloidale Nanopartikel herzustellen. Eine Weiterentwicklung ist die Verwendung von Pulversuspensionen als Ausgangsmaterial. Dies führt zu höheren Produktivitäten und neuen Materialien. Die zugrundeliegenden Prozesse sind allerdings komplex. Um diese Mechanismen aufzuklären, wurde ein chemischer Ansatz gewählt. Als Ausgangsmaterial wurden daher verschiedene Kupferverbindungen (Cu2C2, Cu5Si, Cu3N, Cu(N3)2, Cu3P, Cu2O, CuO, Cu2S, CuS und CuI) verwendet. Die hergestellten Nanopartikel wurden mit Hilfe der analytischen Transmissionselektronenmikroskopie charakterisiert. Dadurch konnten nachgewiesen werden, dass zwei Mechanismen an der Nanopartikelbildung beteiligt sind. Die Laserbestrahlung von Ausgangsmaterialien wie CuO und Cu3N führt zur Bildung von metallischen Kupfernanopartikeln. In dem dabei erzeugten Plasma nukleieren die Kupferatome zunächst zu kleinen primären Nanopartikeln. Diese Partikel koaleszieren anschließend und bilden größere sekundäre Partikel. Im Gegensatz zu dieser reduktiven Ablation, resultiert die Laserbestrahlung von CuI in der Fragmentierung des Materials. In diesem Fall wird kein Plasma erzeugt, sondern der induzierte thermische Stress führt zur Fragmentierung des Kristalls unter Beibehaltung der chemischen Zusammensetzung. Die Frage, welcher der beiden Mechanismen für ein bestimmtes Ausgangsmaterial dominiert, ist entscheidend für potentielle Anwendungen der Methode, da hiervon die chemische Zusammensetzung der erhaltenen Nanopartikel abhängt. Dies wird am Beispiel der Synthese von Bi2Te3 Nanopartikeln diskutiert, die in thermoelektrischen Elementen zur Anwendung kommen können.
The synthesis of colloidal nanoparticles has become a major topic in recent years. The pulsed laser ablation in liquids poses an alternative to the common wet-chemical approaches. Key features of the pulsed laser ablation in liquids are its simple setup, its versatility, and the possibility to generate surfactant-free colloidal nanoparticles. A further development of this technique is the use of suspended powders instead of bulk targets. This leads to higher productivities and even new materials. Although the generation of colloids by irradiating a suspension is straight forward, the underlying mechanisms of the size reduction from micrometer to nanometer sized particles appear to be quite complex. In order to reveal the mechanism a chemical approach was chosen. Hence, various copper compounds (Cu2C2, Cu5Si, Cu3N, Cu(N3)2, Cu3P, Cu2O, CuO, Cu2S, CuS and CuI) were used as a model system in order to investigate the impact of the leaving group on the ablation process. The generated nanoparticles were characterized with analytical transmission electron microscopy. These investigations clearly show that there are two distinct mechanisms involved in nanoparticle formation. The laser irradiation of precursors like CuO and Cu3N results in the formation of metallic copper nanoparticles. In the generated plasma copper atoms nucleate and form small primary particles. These particles later coalesce to larger secondary particles. In contrast to this reductive ablation, the irradiation of CuI follows a fragmentation mechanism. Here, the absorbed power of the laser beam does not produce a plasma but introduces thermal stress leading to fragmentation of the crystal while the chemical composition is preserved. The question which mechanism is predominant is of utmost importance as the chemical composition of the nanoparticles depends on the formation process. This is discussed on the example of the synthesis of Bi2Te3 nanoparticles, which can be used in thermoelectric applications.

Amélioration des propriétés des couches minces de carbone amorphe (appelé Diamond Like Carbon, DLC) et recherche de nouvelles fonctionnalités pour ce type de couches minces en dopant les films DLC par des métaux comme le nickel et le tantale.
L'ablation laser en régime femtoseconde est la technique utilisée pour la synthèse des couches minces de DLC dopées ou alliées. Ce sujet met également en évidence l'apport de cette technique sur les propriétés morpho-structurales et physiques des DLC dopés ou alliés.

Cette thèse décrit la fabrication de couches épaisses nanostructurées magnétostrictives par dépôt supersonique de nanoparticules sur un substrat ; ces nanoparticules étant obtenues par le procédé d'Ablation Laser de Microparticules de Terfenol-D en aérosol. Un bloc solide de Terfenol-D a été réduit en poudre de microparticules de 0,3 à 3 µm de diamètre. Ces microparticules ont ensuite été injectées dans un aérosol s'écoulant en continu et ablaté par un laser ultraviolet KrF pulsé. Puis, les nanoparticules formées après l'ablation ont été accélérées par leur passage dans un micro-orifice. Le jet supersonique de nanoparticules en découlant a été utilisé pour déposer une couche épaisse sur un substrat à température ambiante. Les nanoparticules étaient amorphes, comme l'ont montré les analyses de diffraction aux rayons X des couches et les mesures de microscopie électronique à transmission (TEM) effectuées sur des particules individuelles. La distribution des tailles des nanoparticules était typique du procédé LAM : entre 3 et 20 nm de diamètre avec une moyenne de moins de 10 nm.
Les couches déposées ont été caractérisées par la méthode des poutres pour déterminer le module élastique et le niveau de magnétostriction. Les couches étant poreuses en raison de leur nature granulée, leur module élastique était réduit à environ 15 GPa. Le niveau de magnétostriction des couches était d'environ 15 ppm ; cette magnétostriction réduite (1/30 de celui des couches fines) étant dû à un problème d'oxydation. Une analyse spectroscopique du plasma produit par l'ablation a permit la détermination de la source d'oxydation. L'étendue de l'oxydation des couches est apparue directement dépendante de la taille des microparticules utilisées initialement pour fabriquer les nanoparticules. Après calculs théoriques, pour des densités typiques d'aérosol utilisées dans le procédé LAM, il a été démontré que les nanoparticules fabriquées à partir de microparticules de plus de 3 µm de diamètre n'étaient pas affectées de façon significative par les impuretés présentes dans le gaz ou par l'oxydation de surface des microparticules. En revanche, les nanoparticules fabriquées à partir de microparticules de 0,3 µm de diamètre ou moins étaient, elles, oxydées et les couches en résultant l'étaient aussi. Experimentalement le diamètre des microparticules injectées en aérosol était présumé être entre ces deux cas.

In this study we applied ultra-short laser pulses on a biological sample (Arabidopsis), in order to cut it precisely in a square pattern and subsequently use it for studying stress generation mechanisms. For this purpose, we utilized femtosecond laser pulses at 100 fs pulse width and 80 MHz repetition rate. We took two processing parameters into consideration such as laser power, laser exposure time which is related to the stage speed. Therefore, we were able to find the laser optimum conditions for ablation of biological tissues. The mutant and wildtype (control) obtained from laser cutting with a size of 500 µm × 500 µm were directly transferred (in-situ with laser cutting) into a microfabricated chamber containing ~500 nanoliters deionized water for measuring ion conductivity. The ion conductivity is a signature of cell-death mechanisms caused by various stresses. A light with intensity of 100 µmol was exposed to the samples for 2 hours and 20 minutes as a source of stress. A quantitative electrical analysis with high accuracy was assured by utilizing a microchamber, which enables a measurement in nanoliter volume. We measured the impedance which is reciprocal of conductivity using a lock-in amplifier and a precise current source at frequency of 130 Hz. Initially high impedance of mutant sample tended to drop within 2 hours and finally approached the constant value which signified that the cell death mechanism was complete. However, the wildtype sample demonstrated approximately constant impedance (conductivity) during the experiment.

Modeling the atmospheric entry of spacecraft is challenging because of the large number of physical phenomena that occur during the process. In order to study thermal protection systems, engineers rely on high fidelity solvers to provide accurate predictions of both the thermochemical environment surrounding the heat shield, and its material response. Therefore, it is necessary to guarantee that the numerical models are correctly implemented and thoroughly validated. In recent years, a high-fidelity modeling tool has been developed at the University of Kentucky for the purpose of studying atmospheric entry. The objective of this work is to verify and validate this code. The verification consists of the development of an automated regression testing utility. It is intended to both aid code developers in the debugging process, as well as verify the correct implementation of the numerical models as these are developed. The validation process will be performed through comparison to relevant ablation experiments, namely arc-jet tests. Two modules of the code are used: fluid dynamics, and material response. First the fluid dynamics module is verified against both computational and experimental data on two distinct arc-jet tests. The material response module is then validated against arc-jet test data using PICA.

Modifications were made to the turbulent channel flow facility to allow for fully developed rough quasi-2D Poiseuille flow with flow injection through one surface and flow suction through the opposing surface. The combination of roughness and flow injection is designed to be analogous to the flow field over a thermal protection system which produces ablative pyrolysis gases during ablation. It was found that the additional momentum through the surface acted to reduce skin friction to a point below smooth-wall behavior. This effect was less significant with increasing Reynolds number. It was also found that the momentum injection modified the wake region of the flow.

Since the 1970's, NASA has relied on the use of rigid aeroshells and supersonic parachutes to enable robotic mission to Mars. These technologies are constrained by size and deployment condition limitations that limit the payload they can deliver to the surface of Mars. One candidate technology envisioned to replace the supersonic parachute is the supersonic inflatable aerodynamic decelerator (IAD). This dissertation presents an overview of work performed in maturing a particular type of IAD, the tension cone. The tension cone concept consists of a flexible shell of revolution that is shaped so as to remain under tension and resist deformation. Systems analyses that evaluated trajectory impacts of a supersonic IAD demonstrated several key advantages including increases in delivered payload capability of over 40%, significant gains in landing site surface elevation, and the ability to accommodate growth in the entry mass of a spacecraft. A series of supersonic wind tunnel tests conducted at the NASA Glenn and Langley Research Centers tested both rigid and flexible tension cone models. Testing of rigid force and moment models and pressure models demonstrated the new design to have favorable performance including drag coefficients between 1.4 and 1.5 and static stability at angles of attack from 0º to 20º. A separate round of tests conducted on flexible tension cone models showed the system to be free of aeroelastic instability. Deployment tests conducted on an inflatable model demonstrated rapid, stable inflation in a supersonic environment. Structural modifications incorporated on the models were seen to reduce inflation pressure requirements by a factor of nearly two. Through this test program, this new tension cone IAD design was shown to be a credible option for a future flight system. Validation of CFD analyses for predicting aerodynamic IAD performance was also completed and the results are presented. Inviscid CFD analyses are seen to provide drag predictions accurate to within 6%. Viscous analyses performed show excellent agreement with measured pressure distributions and flow field characteristics. Comparisons between laminar and turbulent solutions indicate the likelihood of a turbulent boundary layer at high supersonic Mach numbers and large angles of attack.

Space vehicles, while entering the planetary atmosphere, experience high loads of heat. Ablative materials are commonly used for a thermal protection system, which undergo mass removal mechanisms to counter the heat rates. Spallation is one of the ablative processes, which is characterized by the ejection of solid particles from the material into the flow. Numerical codes that are used in designing the heat shields ignore this phenomenon. Hence, to evaluate the effectiveness of spallation phenomenon, a numerical model is developed to compute the dynamics and chemistry of the particles. The code is one-way coupled to a CFD code that models high enthalpy flow field around a lightweight ablative material. A parametric study is carried out to examine the variations in trajectories with respect to ejection parameters. Numerical results are presented for argon and air flow fields, and their effect on the particle behavior is studied. The spallation code is loosely coupled with the CFD code to evaluate the impact of a particle on the flow field, and a numerical study is conducted.

L'émission d'ultrasons focalisés à forte puissance peut être utilisée pour réaliser l'ablation non-invasive de zones pathogènes, de type cancéreuses par exemple. On distingue deux régimes d'ablations : ablation thermique appelée HIFU (" High Intensity Focused Ultrasound ") et ablation mécanique appelée histotripsie utilisant des ondes de chocs focalisées. Au cours de ma thèse, nous avons développé des méthodes de suivi ultrasonore en temps réel à partir d'une technique d'élastographie quantitative (Supersonic Shear wave Imaging). Nous montrerons que des mesures précises des changements d'élasticité au cours des traitements fournissent un suivi et un guidage avec une robustesse aux mouvements du patient. En effet, l'élastographie nous a permis d'une part de cartographier la température et d'autre part de suivre la formation de lésion en temps réel qu'elle soit de type thermique (HIFU) ou mécanique (histotripsie). Nous aborderons aussi une technique d'inversion totale du front d'onde appliquée à SSI qui améliore la sensibilité à la perte d'information due au bruit et à l'hypoéchogénicité existante dans certaines lésions. Enfin, nous présenterons un nouveau concept de cavité à retournement temporel " réglable " pour l'émission d'impulsions de très fortes pressions à partir d'un nombre limité de transducteurs. Notre prototype a permis de générer des ondes de chocs focalisées au sein d'une étendue considérable et de multiplier par 17 la pression d'une sonde d'imagerie conventionnelle. Ainsi, à partir d'électroniques basse-puissance à faible coût, ce dispositif thérapeutique pourrait avoir de nombreuses applications thérapeutiques limitées actuellement par des contraintes géométriques.

碩士
國立中山大學
生物醫學研究所
96
Breast cancer is the fifth most common cause of cancer death in the worldwide. In the past decades, tamoxifen has been used for clinical treatment for breast cancers. The derivatives of compound thiazolidinedione (TZDs) including troglitazone (rezulin) and rosiglitazone (avandia) are also in the stages of clinical trials. But in the earlier research, some studies reported that the use of these drugs was associated with some serious side effects. Cyclin D1 plays an important role in G1/S phase cell cycle progression and in growth factor- or estrogen-induced mammary epithelial cell proliferation. Cyclin D1 overexpression is also found in high percentage (over 30%) of human breast cancers, correlating with poor prognosis. In this study, we used a cyclin D1-ablative drug VGH No.47 to reduce the expression of cyclin D1 in human breast adenocarcinoma cell line MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) and to study its effect on cell proliferation. Our results demonstrated that VGH No.47 decreased the protein stability of cyclin D1. Conversely, VGH No.47 reduced cyclin D1 at both transcriptional level and protein stability in ER-negative MDA-MB-231 cells. We found that VGH No.47 caused G2/M arrested in both breast cancer cell lines. In addition, we tested whether cyclin D1-ablative drug could sensitize breast cancer cells to tamoxifen and TZDs. We expect to lower the dose of tamoxifen, troglitazone or rosiglitazone to reduce the side effects, but the results do not meet our expectation and do not exhibit synergistic effect.

博士
國立陽明大學
臨床醫學研究所
101
Background: Inflammation is an important mechanism in the pathogenesis of atrial fibrillation (AF). It remains unclear if inflammation is associated with the outcome of AF after catheter ablation. Furthermore, the patho-physiological process of AF recurrence and its associated cytokines and inflammatory pathways are also not clear. Methods: We enrolled prospective patients receiving catheter ablation for AF and tracked the recurrence of AF for 1 to 2 years. Different inflammation associated pathways and cytokines were screened using different methods, such as flow cytometry, real-time polymerase chain reaction (RT-PCR), and ELISA. Monocyte expression of CD36 was determined by flow cytometry. Heat shock protein 27 (HSP27), tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), and HSP70 were detected by ELISA. High-sensitivity CRP (HsCRP) was determined using particle-enhanced immunoturbidimetry. Hemoxygenase-1 (HO-1) gene promoter polymorphisms and mRNA were determined using RT-PCR. Results: Of the screened cytokines or biomarkers, lower levels of monocyte CD36 protein and lower serum levels of HSP27 were independently associated with AF, but these variables were not associated with changes in TNF-α, IL-10, C-reactive protein, HSP70, or hemoxygenase-1 (HO-1) gene promoter polymorphisms. Monocyte CD36, HSP27, and HO-1 gene promoter polymorphisms were independently associated with AF recurrence after catheter ablation using a Kaplan–Meier analysis from different cohorts. CD36 and HSP27 were associated with different electro-anatomic properties, such as left atrial diameter and left atrial mean voltage. HSP27 levels were associated with non-pulmonary ectopies and fractionated intervals. An analysis of mRNA levels from the buffy coat revealed that CD36 levels were positively correlated with IL-10 levels but were inversely correlated with PPAR-γ and TNF-α levels. Similarly, HSP27 levels were inversely associated with TNF-α and positively correlated with IL-10, as indicated by both ELISA and mRNA, indicating the role of anti-inflammation. However, CD36 did not interact with HSP27. CD36 regulated monocyte inflammation, and HSP27 was associated with different lymphocyte levels, but not neutrophil levels. These findings suggest that chronic inflammation plays a more important role than acute inflammation. From the literature, HO-1 gene promoter polymorphisms have been associated with different inflammatory statuses. However, in the present study, we did not see an association between the number of GT repeats and CRP, IL-10, or TNF-α, implying other inflammatory pathways or alternative mechanisms such as anti-apoptosis may be involved. Conclusions: Specific inflammatory pathways such as monocyte CD36, HSP27S levels, and HO-1 gene promoter polymorphisms correlated with electro-anatomical remodeling and predicted AF recurrence after catheter ablation.

Η θεραπεία των καλοήθων οστικών όγκων εξαρτάται από την ανατομική εντόπιση, τα συμπτώματα, τη φυσική ιστορία του όγκου και τη θνησιμότητα της θεραπείας η οποία στις περισσότερες περιπτώσεις περιλαμβάνει ή την εκτομή ή την απόξεση αν και όχι σπάνια είναι απαραίτητο να πραγματοποιηθεί μία ευρύτερη εξαίρεση, χρησιμοποιώντας τις ίδιες αρχές όπως στους κακοήθεις οστικούς όγκους. Οι νεότερες διαδερμικές μέθοδοι, με κυριότερο εκπρόσωπο τη διαδερμική θερμοκαυτηρίαση (RFA) έρχονται να δώσουν τη λύση, εξασφαλίζοντας την πλήρη καταστροφή του όγκου αλλά και τη διατήρηση της λειτουργικής κινητικότητας του ασθενούς. Η παρούσα μελέτη εξέτασε την αποτελεσματικότητα και την ασφάλεια της εν λόγω θεραπευτικής μεθόδου στην αντιμετώπιση κατά κύριο λόγο των οστεοειδών οστεωμάτων αλλά και άλλων καλοήθων οστικών όγκων, όπως τα χονδροβλαστώματα και τα οστεοβλαστώματα. Επίσης, μελετήθηκαν τα απεικονιστικά πρότυπα των όγκων πριν και μετά RFA και έγινε συσχέτιση των απεικονιστικών αποτελεσμάτων με άλλες παραμέτρους των υπό μελέτη οστικών όγκων. ΥΛΙΚΟ ΚΑΙ ΜΕΘΟΔΟΣ Από τον Δεκέμβριο του 2003 έως και τον Δεκέμβριο του 2009 συνολικά 33 ασθενείς με συνολικά 33 καλοήθεις οστικούς όγκους υποβλήθηκαν σε διαδερμική θερμοκαυτηρίαση με ραδιοσυχνότητες (κατόπιν ενυπόγραφης πληροφορημένης συναίνεσης). Από τους 33 καλοήθεις όγκους, οι 29 ήταν οστεοειδή οστεώματα, οι τρεις χονδροβλαστώματα και ο ένας οστεοβλάστωμα. Από τους 33 ασθενείς, οι 23 ήταν άντρες και οι 10 γυναίκες (♂/♀: ~2/1), ηλικίας από 11 έως 39 ετών (μέση ηλικία : 22,5 έτη). Η διάμετρος των οστεοειδών οστεωμάτων κυμαίνονταν από 4 έως 12 χιλ. (μέση τιμή:7 χιλ.), των χονδροβλαστωμάτων από 26 έως 32 χιλ. (μέση τιμή:29 χιλ.) και του οστεοβλαστώματος 32 χιλ. Συνολικά 27 (82%) όγκοι εντοπίζονταν στα κάτω άκρα, τέσσερις (12%) στα άνω άκρα και δύο (6%) στην σπονδυλική στήλη. Οι έντεκα (33%) από τις 33 βλάβες είχαν ενδαρθρική εντόπιση. Η διάγνωση των οστεοειδών οστεωμάτων στηρίχθηκε αποκλειστικά σε ακτινολογικά και κλινικά κριτήρια, ενώ για τα χονδροβαλστώματα και το οστεοβλάστωμα πραγματοποιήθηκε βιοψία. Σε όλους τους όγκους η θερμοκαυτηρίαση πραγματοποιήθηκε με τη χρήση ενός άκαμπτου RF ηλεκτροδίου σε σχήμα «ράβδου» εκτός από δύο περιπτώσεις χονδροβλαστωμάτων της μηριαίας κεφαλής όπου χρησιμοποίηθηκε εκπτυσσόμενο RF ηλεκτρόδιο δίκην «ομπρέλας». Καταγράφηκαν και μελετήθηκαν τα ποσοστά επιτυχίας, οι υποτροπές, οι επιπλοκές καθώς και τα αποτελέσματα της στατιστικής ανάλυσης. ΑΠΟΤΕΛΕΣΜΑΤΑ Η μέθοδος ήταν τεχνικά επιτυχής και στους 33 όγκους (100%). Υποτροπή των συμπτωμάτων παρουσιάστηκε σε τρεις περιπτώσεις (9%, 3/33) οστεοειδών οστεωμάτων (ένα ενδαρθρικό στο σπογγώδες οστό και δύο εξω-αρθρικά στην φλοιώδη μοίρα), αντίστοιχα στους δύο, έξι και τέσσερις μήνες μετά την «θερμοκαυτηρίαση» (μέση τιμή : 4 μήνες). Η μη σωστή τοποθέτηση του RF ηλεκτροδίου μέσα στον όγκο και ο τραυματισμός του αρθρικού χόνδρου ήταν οι λόγοι αποτυχίας της μεθόδου. Ο ένας ασθενής υπεβλήθη σε δεύτερο επιτυχή «θερμοκαυτηριασμό» (εξω-αθρικό, φλοιώδες οστεοειδές οστέωμα), ο δεύτερος ακολούθησε τη χειρουργική οδό (εξω-αθρικό, φλοιώδες οστεοειδές οστέωμα) και ο τρίτος συνέχισε τη φαρμακευτική αγωγή (ενδαρθρικό, σπογγώδες οστεοειδές οστέωμα). Έτσι, τα ποσοστά κλινικής επιτυχίας μετά την 1η RF συνεδρία ανέρχονται στο 91% (30/33) και συνολικά μετά και την 2η RF συνεδρία ανέρχονται τελικά στο 94% (31/33). Η περίοδος κλινικής παρακολούθησης κυμάνθηκε συνολικά για όλους τους όγκους από 6 έως 70 μήνες (μέση τιμή follow-up : 28 μήνες). Στις επιπλοκές περιλαμβάνονται μία περίπτωση θερμικής δερματικής κάκωσης 1ου βαθμού (ελάσσονα επιπλοκή), μία περίπτωση ιατρογενούς- εκφυλιστικής οστεοαρθρίτιδας (3η υποτροπή) και μία περίπτωση σηπτικής αρθρίτιδας της αριστερής κατά γόνυ αρθρώσεως με σχηματισμό δερματικού συριγγίου δύο μήνες μετά RFA που αντιμετωπίστηκε χειρουργικά. Για τις 25 (86%, 25/29) συνολικά περιπτώσεις οστεοειδών οστεωμάτων με διαθέσιμο CT follow-up πριν και μετά τη θερμοκαυτηρίαση (6, 12 και 24 μήνες), πραγματοποιήθηκε στατιστική συσχέτιση πολλαπλών μεταβλητών και προέκυψαν τα κάτωθι συμπεράσματα (Kendall’s t-test): 1) Η ελάχιστη ή και μηδαμινή «οστεοποίηση» της «φωλεάς» δεν υποδεικνύει απαραίτητα την κλινική αποτυχία (P=0.14). 2) Η ανίχνευση εσωτερικής «οστεοποίησης» της «φωλεάς» παρουσίασε έντονη θετική συσχέτιση με την μεγάλη (≥12 μήνες) διάρκεια του CT follow-up (P=0.014). 3) Το μεγάλο μέγεθος των οστεοειδών οστεωμάτων (>7 χιλ.) συσχετίζεται έντονα αρνητικά με την φλοιώδη (P=0.001), την εξωαρθρική (P=0.003) και την διαφυσιακή εντόπιση (P=0.001). 4) Επίσης και το μεγάλο (≥ 7χιλ.) μέγεθος (P=0.086), δηλαδή και το μεγάλο μέγεθος τείνει να συσχετίζεται με την «ωριμότητα» του όγκου (παρουσία εσωτερικών αποτιτανώσεων προ RFA) . Στοιχεία εσωτερικής «οστεοποίησης» (μετά RFA) ανεδείχθησαν ήδη με την συμπλήρωση των 12 μηνών από την θερμοκαυτηρίαση για δύο χονδροβλαστώματα ενώ το τρίτο εμφάνισε σχεδόν πλήρη «οστεοποίηση» στους 48 μήνες απεικονιστικού follow-up. Απ’ την άλλη, δεν παρατηρήθηκε αλλαγή στην απεικόνιση του οστεοβλαστώματος της κερκίδας στο εξάμηνο ακτινολογικό follow-up. Μέχρι σήμερα όλα τα περιστατικά των χονδροβλαστωμάτων και του οστεοβλαστώματος παραμένουν –από κλινικής απόψεως- ελεύθερα άλγους ή κινητικής δυσχέρειας. ΣΥΜΠΕΡΑΣΜΑ Η διαδερμική θερμοκαυτηρίαση με ραδιοσυχνότητες (RF Ablation) είναι μία ελάχιστα επεμβατική θεραπευτική επιλογή για τους ασθενείς με οστεοειδή οστεώματα, η οποία παρέχει άμεση ανακούφιση από το άλγος με χαμηλά ποσοστά επιπλοκών και υποτροπών. Η RF θερμοκαυτηρίαση θεωρείται πλέον ως η θεραπεία εκλογής για τα οστεοειδή οστεώματα του περιφερικού σκελετού και της πυέλου αλλά και για τις χειρουργικές υποτροπές. Μειώνει την ενδονοσοκομειακή νοσηλεία και τη διάρκεια της επαναφοράς και αποκατάστασης του ασθενούς. Η οστική βιοψία πριν την RF θεραπεία δεν είναι απαραίτητη εφ’ όσον η διάγνωση μπορεί με ασφάλεια να βασιστεί στα κλινικά και απεικονιστικά ευρήματα. Η αξιολόγηση της κλινικής πορείας και όχι η απεικόνιση είναι το καλύτερο κριτήριο για να γίνει διάκριση μεταξύ των ασθενών με καλή ή όχι κιλινική έκβαση. Η καταγραφή και η συσχέτιση παραμέτρων, όπως το μέγεθος, η θέση και η παρουσία εσωτερικών αποτιτανώσεων των οστεοειδών οστεωμάτων δύναται να βοηθήσουν στην κατανόηση της παθογένεσής τους. Η μέθοδος, σε επιλεγμένες περιπτώσεις (θέση-μέγεθος) και υπό κατάλληλες συνθήκες (πολλαπλές «αλληλοεπικαλυπτόμενες» RF συνεδρείες μικρότερης «ενεργού» ακτίνας), μπορεί να εφαρμοστεί επιτυχώς και σε άλλους καλοήθεις οστικούς όγκους όπως τα χονδροβλαστώματα και τα οστεοβλαστώματα.
Treatment of benign primary bone tumors depends on the anatomical location, symptoms, the natural history of the tumor and the morbidity of treatment and in most cases involves either simple excision or curettage although occasionally it is necessary to perform a complete excision using the same principles as for malignant tumors. CT-guided radiofrequency ablation (RFA), has emerged as minimally invasive alternative to destroy the tumor, overcome surgical difficulties and potential hazards and preserve the functional ability of the patient. The present study demonstrates the healing effect of RFA and evaluates its efficacy and safety in the treatment of osteoid osteomas, chondroblastomas and osteoblastomas. Additionally, this series compare the imaging pattern of the bone tumors prior and post RFA and correlate the results with other selected tumor parameters. MATERIAL AND METHODS From December 2003 to December 2009 a total number of 33 patients (23 male, 10 female, 11-39 years, mean: 22, 5 years) with 33 benign bone tumors were treated with RFA. Informed consent and institutional board approval were obtained. The tumors consisted of 29 osteoid osteomas, three biopsy-proved chondroblastomas and one biopsy-proved osteoblastoma. The mean maximum diameter was 7mm (range: 4-12 mm) for osteoid osteomas, 29 mm for chondroblastomas (range: 26-32 mm) and 32mm for the osteoblastoma. Lesions were located in the limbs (n: 27, 82%), the upper arm (n: 4, 12%) and two in the spine (n: 2, 6%). Intra-articular location was detected in 11(33%) tumors. Diagnosis of osteoid osteomas was base on imaging and clinical criteria. Ablation was performed using a straight rigid RF electrode in 31 tumors while a multi-tined expandable RF electrode was used in two cases of femoral chondroblastomas. Primary success rate, total secondary success rate, recurrences, complications, follow-up and statistical analysis results were assessed. RESULTS Technical success was achieved in 33 patients (33/33, 100%). Recurrence occurred in three osteoid osteomas (3/33, 9%); one intra-articular medullar lesion and two extra-articular cortical lesions at two, six and four months post RFA respectively (mean: 4 months). Failure was attributed to inadequate RF electrode positioning in the cortical lesions whilst articular damage was the main reason for pain relapse in the third intra-articular case. Primary success rate was 91% and total secondary success rate was 94%. Mean clinical follow-up period was 28 months (range: 6-70 months) for all lesions. Complications comprised of one mild thermal skin injury, one hip joint degenerative arthritis (third intra-articular failure case) and a case of septic arthritis with bony changes and cutaneous fistula, due to wound infection, which required surgical debridement. Statistical analysis of bone tumor parameters regarding 25 cases of osteoid osteomaswith available CT-follow-up, like complete, partial or absent ossification of the treated nidus, patient age and sex, tumor size and location, pre-existing calcifications, clinical outcome and CT follow-up, reached the following results (Kendall’s t-test): 1) Absence and/or minimal of post RFA ossification does not necessarily indicate clinical failure (P=0.14). 2) Detection of post RFA ossification showed an intense positive correlation with a long-lasting CT follow-up (≥ 12 months) (P= 0.014). 3) The “big” size of osteoid osteomas (>7mm) showed an intense negative correlation with the cortical (P=0.001), extra-articular (P= 0.003) and diaphyseal location (P=0.001). 4) Also, the “big” size of osteoid osteomas (>7mm) tends to correlate with the presence of calcifications (prior RFA), which represents a “maturity” marker of the tumor (P= 0.086). All three cases of chondroblastomas showed signs of internal ossification post RFA on regular imaging follow-up while the osteoblastoma did not show any imaging changes on the 6-month follow-up. On the other hand, the osteoblastoma and the remaining three cases of chondroblastomas presented an excellent post RFA clinical course without any signs of relapse. CONCLUSIONS Percutaneous RFA is a minimally invasive therapeutic option for osteoid osteomas which provides immediate pain relief and low rates of complications and recurrences. It is considered as the treatment of choice for appendicular and pelvic osteoid osteomas and for surgical recurrences as well. Biopsy is not mandatory provided that the diagnosis can be safely based on clinical and imaging grounds. The determination of an adverse clinical outcome should be based on clinical evaluation and not on the imaging pattern. The study and correlation of tumor parameters like size, location and pre-existing calcifications of osteoid osteomas can help in understanding their pathogenesis. The present study also suggests that RFA, when correctly performed, should be included in the treatment algorithm of selected cases of other benign bone tumors like chondroblastomas and osteoblastomas.

Regulation of size and growth is a fundamental problem in biology and often closely related to functionality and fitness. A prominent example is the mitotic spindle, whose size needs to be perfectly tuned to ensure proper chromosome segregation during cell division. It is known that spindle size generally scales with cell volume, most likely as a result of limiting components. However, this relation breaks down in very large cells where spindles have a maximum size. How the size and microtubule mass are set and why spindles show an upper size limit in large cells is still not understood. Spindles mainly consist of highly dynamic short microtubules that turn over very quickly in comparison to the lifetime of the entire structure. Thus, microtubules need to be constantly created throughout the spindle, a process called nucleation. Understanding the role of microtubule nucleation in setting the size of spindles is limited by the fact that little is known about the rate, distribution, and regulation of microtubule nucleation in these structures. This is partly due to the lack of methods to measure microtubule nucleation in spindles. During this work, I developed an assay based on laser ablation to probe microtubule nucleation in monopolar spindles assembled in Xenopus laevis egg extract. Using this new method in combination with quantitative microscopy, I found that microtubule nucleation in these structures is spatially regulated. Furthermore, I observed that nucleation is stimulated by pre-existing microtubules leading to new microtubule growth in their physical proximity. Combining my experimental results on nucleation with theory and further biochemical perturbations, I show that this autocatalytic nucleation mechanism is limited by the availability of active nucleators. In spindles, the amount of active nucleators decreases with distance from the chromosomes. Thus, this mechanism provides an upper limit to spindle size even when resources are not limiting.

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Many minor/trace elements can substitute into the crystal lattice of galena at various concentrations. In-situ LA-ICP-MS analysis and trace element mapping are used to obtain minor/trace element data from a range of natural galena specimens aiming to enhance understanding of the governing factors that control minor/trace element partitioning. The coupled substitution Ag+ + (Bi, Sb)3+ ↔ 2Pb2+, is confirmed by data obtained, although when Bi and/or Sb are present at high concentrations (~> 0.002 mol.%), site vacancies most likely come into play through the additional substitution 2(Bi, Sb)3+ + □ ↔ 3Pb2+. Galena is the primary host of Tl in all mapped mineral assemblages. Thallium is likely incorporated into galena along with Cu through the coupled substitution: (Ag, Cu, Tl)+ + (Bi, Sb)3+ ↔ 2Pb2+. Tin can reach significant concentrations in galena, particularly when the latter formed via metamorphic recrystallisation. Tin is concentrated in galena, likely via the substitution: Sn4+ + □ ↔ 2Pb2+, involving the creation of lattice vacancies, or Sn2+ ↔ Pb2+. Tin and In concentrations show a strong positive correlation across the sample suite indicating that the availability of these elements is intimately linked in natural systems. Cadmium and minor Hg can be incorporated into galena; the simple isovalent substitution (Cd, Hg)2+ ↔ Pb2+ is inferred. Significant oscillatory compositional zoning, and lesser sector zoning of minor/trace elements (Ag, Sb, Bi, Se, Te) is confirmed, for the first time, in galena from two epithermal ores. Zoning is attributed to slow crystal growth into open spaces within the vein at relatively low temperatures. The datasets generated increase understanding of the nature and distribution of minor/trace elements in galena, and partitioning between galena and coexisting minerals. These data have several applications in the minerals industry, particularly in studies of mineral deposit genesis, ore processing and, potentially, also in mineral exploration.
Thesis (B.Sc.(Hons)) -- University of Adelaide, School of Physical Scences, 2013