No description available.

Irreversible electroporation (IRE) is a non-thermal tissue ablation modality in which electrical pulses are used to generate targeted disruption of cellular membranes. Clinically, IRE is administered by inserting one or more needles within or around a region of interest, then applying a series of short, high amplitude pulsed electric fields (PEFs). The treatment effect is dictated by the local field magnitude, which is quite high near the electrodes but dissipates exponentially. When cells are exposed to fields of sufficient strength, nanoscale "pores" form in the membrane, allowing ions and macromolecules to rapidly travel into and out of the cell. If enough pores are generated for a substantial amount of time, cell homeostasis is disrupted beyond recovery and cells eventually die. Due to this unique non-thermal mechanism, IRE generates targeted cell death without injury to extracellular proteins, preserving tissue integrity. Thus, IRE can be used to treat tumors precariously positioned near major vessels, ducts, and nerves. Since its introduction in the late 2000s, IRE has been used successfully to treat thousands of patients with focal, unresectable malignancies of the pancreas, prostate, liver, and kidney. It has also been used to decellularize tissue and is gaining attention as a cardiac ablation technique. Though IRE opened the door to treating previously inoperable tumors, it is not without limitation. One drawback of IRE is that pulse delivery results in intense muscle contractions, which can be painful for patients and causes electrodes to move during treatment. To prevent contractions in the clinic, patients must undergo general anesthesia and temporary pharmacological paralysis. To alleviate these concerns, high-frequency irreversible electroporation (H-FIRE) was introduced. H-FIRE improves upon IRE by substituting the long (~100 µs) monopolar pulses with bursts of short (~1 µs) bipolar pulses. These pulse waveforms substantially reduce the extent of muscle excitation and electrochemical effects. Within a burst, each pulse is separated from its neighboring pulses by a short delay, generally between 1 and 5 µs. Since its introduction, H-FIRE burst waveforms have generally been constructed simply by choosing the duration of constitutive pulses within the burst, with little attention given to this delay. This is quite reasonable, as it has been well documented that pulse duration plays a critical role in determining ablation size. In this dissertation, we explore the role of these latent periods within burst waveforms as well as their interaction with other pulse parameters. Our central hypothesis is that tuning the latent periods will allow for improved ablation size with reduced muscle contractions over traditional waveforms. After gaining a simple understanding of how pulse width and delay interact in vitro, we demonstrate theoretically that careful tuning of the delay within (interphase) and between (interpulse) bipolar pulses in a burst can substantially reduce nerve excitation. We then analyze how pulse duration, polarity, and delays affect the lethality of burst waveforms toward determining the most optimal parameters from a clinical perspective. Knowing that even the most ideal waveform will require slightly increased voltages over what is currently used clinically, we compare the clinical efficacy of two engineered thermal mitigation strategies to determine what probe design modifications will be needed to successfully translate H-FIRE to the clinic while maintaining large, non-thermal ablation volumes. Finally, we translate these findings in two studies. First, we demonstrate that burst waveforms with an improved delay structure allow for enhanced safety and larger ablation volumes in vivo. And finally, we examine the efficacy of H-FIRE in spontaneous canine liver tumors while also comparing the ablative effect of H-FIRE in tumor and non-neoplastic tissue in a veterinary clinical setting. / Doctor of Philosophy / Cancer is soon to become the most common cause of death in the United States. In 2023, approximately 2 million new cases of cancer will be diagnosed, leading to roughly 650 thousand lost lives. Interestingly, about half of newly diagnosed cancers are caught in the early stages before the disease has spread throughout the body. With effective local intervention, these patients could potentially be cured of their malignancy. Surgical removal of the tumor is the gold standard, but it is often not possible due to tumor location, patient comorbidities, or organ health status. In some instances, focal thermal ablation with radiofrequency or microwave energy can be performed when resection is not possible. These treatments entail the delivery of thermal energy through a needle electrode, which causes local tissue damage through coagulation (cooking) of the tissue. However, thermal ablation destroys tissue indiscriminately, meaning that any nearby blood vessels or neural components will also be damaged, which precludes thousands of patients from treatment each year. Irreversible electroporation (IRE) was introduced to overcome these challenges and provide a treatment option for patients diagnosed with otherwise untreatable tumors. IRE uses pulsed electric fields to generate nanoscale pores in cell membranes, which lead to a homeostatic imbalance and cell death. Because IRE is a membrane-based effect, it does not rely on thermal effects to generate cellular injury, which allows it to be administered to tumors that are adjacent to critical tissue structures such as major nerves and vasculature. Though IRE opened the door to treating otherwise inoperable tumors, procedures are technically challenging and require specialized anesthesia protocols. High-frequency irreversible electroporation (H-FIRE) was introduced by our group roughly a decade ago to simplify the procedure through the use of an alternate pulsing strategy. These higher frequency pulses offer several advantages such as limiting muscle contractions and reducing the risk of cardiac interference, both of which were concerns with IRE. However, H-FIRE ablations have been limited in size, and there is limited knowledge regarding the optimal pulsing strategy needed in order to maximize the ratio of therapeutic benefits to undesirable side effects like muscle stimulation and Joule heating. In this dissertation, we sought to understand how different pulse parameters affect these outcomes. Using a combination of computational, benchtop, and in vivo experiments, we comprehensively characterized the behavior of user-tunable pulse parameters and identified optimal methods for constructing H-FIRE protocols. We then translated our findings in a proof-of-principle study to demonstrate the ability of newly introduced waveform designs to increase ablation size with H-FIRE. Overall, this dissertation improves our understanding of how H-FIRE waveform selection affects clinical outcomes, introduces a new strategy for maximizing therapeutic outcomes with minimal side effects, and provides a framework for selecting parameters for specific applications.

No description available.

No description available.

One of the most conspicuous problems in space physics for the last decades has been to theoretically describe how the large parallel electric fields on auroral field lines can be generated. There is strong observational evidence of such electric fields, and stationary theory supports the need for electric fields accelerating electrons to the ionosphere where they generate auroras. However, dynamic models have not been able to reproduce these electric fields. This thesis sheds some light on this incompatibility and shows that the missing ingredient in previous dynamic models is a correct description of the electron temperature. As the electrons accelerate towards the ionosphere, their velocity along the magnetic field line will increase. In the converging magnetic field lines, the mirror force will convert much of the parallel velocity into perpendicular velocity. The result of the acceleration and mirroring will be a velocity distribution with a significantly higher temperature in the auroral acceleration region than above. The enhanced temperature corresponds to strong electron pressure gradients that balance the parallel electric fields. Thus, in regions with electron acceleration along converging magnetic field lines, the electron temperature increase is a fundamental process and must be included in any model that aims to describe the build up of parallel electric fields. The development of such a model has been hampered by the difficulty to describe the temperature variation. This thesis shows that a local equation of state cannot be used, but the electron temperature variations must be descibed as a nonlocal response to the state of the auroral flux tube. The nonlocal response can be accomplished by the particle-fluid model presented in this thesis. This new dynamic model is a combination of a fluid model and a Particle-In-Cell (PIC) model and results in large parallel electric fields consistent with in-situ observations.

This dissertation is a theoretical treatment of the electric field dependence of optical properties such as Quantum Confined Stark (QCS) shifts, Photoluminescence Quenching (PLQ), and Excitonic Mixing in quantum well heterostructures. The reduced spatial dimensionality in heterostructures greatly enhances these optical properties, more than in three dimensional semiconductors. Charge presence in the quantum well from doping causes the potential to bend and deviate from the ideal square well potential. A potential bending that varies as the square of distance measured from the heterostructure interfaces is derived self-consistently. This potential is used to solve the time-independent Schrodinger equation for bound state energies and wave functions within the framework of the Wentzel, Kramers, and Brillouin (WKB) approximation. The theoretical results obtained from the WKB approximation are limited to wide gap semiconductors with large split off bands such as gallium arsenide-gallium aluminum arsenide and indium gallium arsenide—indium phosphide. Quantum wells with finite confinement heights give rise to an energy dependent WKB phase. External electric and magnetic fields are incorporated into the theory for two different geometries. For electric fields applied perpendicular to the heterostructure multilayers, QCS shifts and PLQ are found to be in excellent agreement with the WKB calculations. Orthogonality between electrons and holes gives rise to interband mixing in the presence of an external electric field. On the contrary, intraband mixing between light and heavy holes is not sufficiently accounted for in the WKB approximation.

Ce travail de thèse porte sur l’étude de l’effet du traitement par champs électriques pulsés (CEP) sur différents procédés de séchage et de friture à partir de produits végétaux (pommes de terre et carottes). Les interactions entre différents modes de séchage et de prétraitement ont été étudiées. L’impact du traitement par CEP et du pré-séchage par l’air chaud ou pré-séchage par le vide sur la cinétique de friture et sur la qualité des produits frits ont été analysés. Le prétraitement par CEP entraîne une électro-perméabilisation des membranes cellulaires, ce qui favorise l’accélération des cinétiques de perte en masse (humidité). Les résultats montrent que le temps de séchage a été réduit significativement dans tous les procédés étudiés (séchage par l’air chaud, séchage par microonde, séchage sous vide). L’avantage du traitement par CEP se manifeste également par une diminution au niveau de la température interne du produit séché. Cette température basse présente un avantage notable dans la préservation des composés sensibles à la chaleur (caroténoïdes…). La couleur des échantillons prétraités par CEP puis séchés, gardent mieux la coloration initiale et présente une déviation réduite en termes de couleur après réhydratation. En ce qui concerne le procédé de friture, l’application du traitement par CEP montrent un avantage en termes de temps de friture mais également en termes de la teneur en huile absorbée. En effet, cette teneur en huile est moins élevée pour le cas des échantillons traités électriquement comparés aux échantillons non traités. La combinaison du CEP et du pré-séchage à l’air chaud (ou du pré-séchage sous vide) montre une réduction importante du temps de friture et également en terme de teneur en huile absorbée. / This research project focuses on the effect of pulsed electric field (PEF) treatment on various drying and frying processes from plant products (potatoes and carrots). Interactions between different drying modes and pretreatment have been studied. The impact of PEF treatment and pre-drying by hot air or pre-drying by vacuum drying on frying kinetics and the quality of fried products were analyzed. PEF pretreatment results in electro-permeabilization of the cell membranes, which favors the acceleration of mass transfer processes. The results showed that the drying time was significantly reduced in all processes (hot air drying, microwave drying, vacuum drying). The advantage of the PEF treatment was also manifested by a decrease of the internal temperature of the product during drying. This lower temperature has a significant advantage in the preservation of heat-sensitive compounds (carotene, etc.). The dried sample pretreated by PEF could better retain the initial product color and had a reduced color deviation after rehydration. In regards to the frying process, the application of the PEF treatment showed not only an advantage in terms of the frying time but also in terms of oil content absorbed. The oil content of PEF treated sample was lower compared to untreated ones. Moreover, the combination of the PEF pretreatment and hot air pre-drying (or vacuum pre-drying) showed a synergistic efficiency on frying time and also in terms of oil content absorbed.

Thesis. 1978. Ph.D.--Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING. / Bibliography: leaves 248-250. / Ph.D.

Cette étude s’inscrit dans le domaine de la description de la dynamique des ceintures deradiation terrestres. Elle consiste à modéliser le phénomène de diffusion radiale en travaillantavec une résolution spatio-temporelle plus fine que celle utilisée pour décrire la dynamiquedes ceintures par le biais d’une équation de diffusion. La démarche s’est organisée en troistemps. Tout d’abord, l’objectif a été d’étudier le phénomène de diffusion radiale d’un point devue théorique afin de mettre en lumière les principaux pilotes du processus et d’expliciter uneformulation des coefficients de diffusion radiale. Une fois l’expression de ces coefficientsétablie, l’objectif a ensuite été de les quantifier. Pour cela, nous avons développé desprotocoles analytiques et numériques puis des protocoles expérimentaux. Nous avons discutéles résultats obtenus ainsi que les atouts et les limites de ces protocoles. Cette étude met enévidence le rôle central de l’asymétrie des variations du champ électromagnétique et deschamps électriques induits dans le processus de diffusion radiale. Elle propose des pistes pourla quantification numérique et expérimentale de ces deux pilotes. Elle apporte également unregard critique sur les travaux de la littérature. Elle ouvre la voie pour une nouvellequantification des coefficients de diffusion basée sur une modélisation adéquate de ladynamique de l’environnement électromagnétique / This study falls within the field of the Earth’s radiation belt dynamics. It consists of modelingthe radial diffusion process based on a spatiotemporal resolution higher than the resolution atwhich radiation belt dynamics are described in terms of a diffusion equation. The approachhas been organized in three parts. First, we described radial diffusion theoretically,highlighting the main drivers of the phenomenon and giving a ready-made formula of theradial diffusion coefficients. Then, based on this formula, we aimed to quantify the radialdiffusion coefficients. In order to reach this goal, we developed analytical and numericalprocedures, and then, observational procedures. Finally, we discussed the results and the prosand cons of each method. This study highlights the central role of asymmetric variations ofthe electromagnetic fields and induced electric fields in the driving of the intensity of theradial diffusion process. It provides tracks for numerical and experimental quantification ofthese two drivers. It also provides tools for a critical review of the literature. It paves the wayfor a more accurate determination of radial diffusion coefficients based on a more precisedescription of the electromagnetic environment and its variations.

<p>One of the most conspicuous problems in space physics for the last decades has been to theoretically describe how the large parallel electric fields on auroral field lines can be generated. There is strong observational evidence of such electric fields, and stationary theory supports the need for electric fields accelerating electrons to the ionosphere where they generate auroras. However, dynamic models have not been able to reproduce these electric fields. This thesis sheds some light on this incompatibility and shows that the missing ingredient in previous dynamic models is a correct description of the electron temperature. As the electrons accelerate towards the ionosphere, their velocity along the magnetic field line will increase. In the converging magnetic field lines, the mirror force will convert much of the parallel velocity into perpendicular velocity. The result of the acceleration and mirroring will be a velocity distribution with a significantly higher temperature in the auroral acceleration region than above. The enhanced temperature corresponds to strong electron pressure gradients that balance the parallel electric fields. Thus, in regions with electron acceleration along converging magnetic field lines, the electron temperature increase is a fundamental process and must be included in any model that aims to describe the build up of parallel electric fields. The development of such a model has been hampered by the difficulty to describe the temperature variation. This thesis shows that a local equation of state cannot be used, but the electron temperature variations must be descibed as a nonlocal response to the state of the auroral flux tube. The nonlocal response can be accomplished by the particle-fluid model presented in this thesis. This new dynamic model is a combination of a fluid model and a Particle-In-Cell (PIC) model and results in large parallel electric fields consistent with in-situ observations.</p>