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Malignant gliomas (MG), most notably glioblastoma multiforme (GBM), are among the most aggressive of all malignancies. High-grade variants of this type of brain cancer are generally considered incurable with singular or multimodal therapies. Many patients with GBM die within one year of diagnosis, and the 5-year survival rate in people is approximately 10%. Despite extensive research in diagnostic and therapeutic technologies, very few developments have emerged that significantly improve survival over the last seven decades. Irreversible electroporation (IRE) is a new non-thermal focal tissue ablation technique that uses low-energy electric pulses to destabilize cell membranes, thus achieving tissue death. The procedure is minimally invasive and is performed through small electrodes inserted into the tissue with treatment duration of about one minute. The pulses create an electric field that induces an increase in the resting transmembrane potential (TMP) of the cells in the tissue. The induced increase in the TMP is dependent on the electric pulse parameters. Depending on the magnitude of the induced TMP the electric pulses can have no effect, transiently increase membrane permeability or cause spontaneous death. In this dissertation we hypothesize that irreversible electroporation is capable of ablating normal (gray and white matter) and pathological (MG and/or GBM) brain tissue in a highly focused non-thermal manner that is modulated through pulse parameters and electrode configuration. Through a comprehensive experimental and numerical investigation, we tested and attained results strongly supporting our hypothesis. Specifically, we developed numerical models that were capable of simulating an entire IRE treatment protocol and would take into account pulse parameters (e.g. duration, frequency, repetition rate and strength) in addition to the dynamic changes in tissue electrical conductivity due to electroporation and joule heating, as well as biologically relevant processes such as blood perfusion and metabolic heat. We also provided a method to isolate the IRE effects from undesired thermal damage in models that were validated with real-time temperature measurements during the delivery of the pulses. Finally we outlined a procedure to use 3D volumetric reconstructions of IRE lesions using patient specific MRI scans in conjunction with the models described for establishing field thresholds or performing treatment planning prior to the surgical procedure; thus supplying the readers with the tools and understanding necessary to design appropriate treatment protocols for their specific application. Experimentally we presented the first systematic in vivo study of IRE in normal canine brain and the multimodal treatment of a canine MG patient. We confirmed that the procedure can be applied safely in the brain and was well tolerated clinically. The lesions created with IRE were sub-millimeter in resolution and we achieved 75% tumor volume reduction within 3 days post-IRE in the patient. In addition to the sharp delineation between necrotic and normal brain, the treatments spared the major blood vessels, making it appropriate for treatment of tumors adjacent to, or enveloping critical vascular structures. We believe that irreversible electroporation will play a key role in the treatment of intracranial disorders including malignant brain cancer in which the intent is to focally kill undesired tissue while minimizing damage to surrounding healthy tissue. / Ph. D.

Orientador: Munemasa Machida / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-08-24T01:40:20Z (GMT). No. of bitstreams: 1 Aguera_JoaoJulioMendes_M.pdf: 1866218 bytes, checksum: 21fe14d8d370e0121be6f854084afb06 (MD5) Previous issue date: 2013 / Resumo: Os plasmas DBD, Descargas com Barreira de Dielétrico, em pressões atmosféricas têm despertado grande interesse nas pesquisas nos últimos anos, principalmente pelas suas aplicações práticas: deposição de materiais, tratamento de superfícies, tratamento de cáries, esterilização de bactérias e destruição de células cancerígenas. Estes plasmas são chamados de plasmas não-térmicos e diferem dos plasmas de alta temperatura (estelares e de reatores de fusão nuclear) e dos plasmas térmicos (tochas de plasmas e plasmas industriais), por possuírem temperaturas translacional, eletrônica, vibracional e rotacional distintas. Para determinar a temperatura de plasmas DBD em descargas elétricas nos gases Ar e He, utilizamos um método indireto que avalia a temperatura por meio de um plasma de Nitrogênio molecular formado pela colisão dos plasmas de Ar e He com o Nitrogênio presente no ar. O espectro luminoso deste plasma é medido, as principais linhas de emissão catalogadas e depois analisado com um software específico para determinação de temperaturas de gases moleculares. Também são mostradas aqui algumas das principais técnicas de espectroscopia usadas na captação de espectros luminosos de plasmas laboratoriais, realizadas em dois dispositivos, plasma DBD produzido com jato de seringa, e plasma fracamente ionizado produzido com uma descarga DC entre dois eletrodos / Abstract: Research on DBD (Dieletrical Barrier Discharges) plasmas at atmospheric pressure have attracted attention and great interest on its research upon the last few years, mostly because of its practical applications: material deposition, surface treatment, cavity treatment, bacterial sterilization and cancer cell destruction. These plasmas are called nonthermal plasmas and differ from the high temperature plasmas (stellar and fusion reactors) and thermal plasmas (plasma torches and industrial plasmas) because of its distinct translational, electronic, vibrational and rotational temperatures. For temperature determination in DBD plasmas formed by electrical discharges on Ar and He gases, an indirect method is used evaluating the temperature of molecular nitrogen plasma formed by collision between the Ar and He plasmas with the nitrogen present in air. The luminous specter of this plasma is measured, the principal emission lines cataloged and then analyzed with specific software for molecular gases temperature determination. The main spectroscopic techniques used for analysis of the luminous spectra obtained from two devices: DBD plasma generated by a syringe jet and weakly ionized plasma produced by a DC discharge between two electrodes, are show on this thesis / Mestrado / Física / Mestre em Física

Background: Bacterial contamination of surfaces with methicillin-resistant Staphylococcus aureus (MRSA) is a serious problem in the hospital environment and is responsible for significant nosocomial infections. The pathogenic contaminants form biofilms, which are difficult to treat with routine biocides. Thus, a continuous search for novel disinfection methods is essential for effective infection control measures. This demonstration of a novel technique for the control of virulent pathogens in planktonic form as well as in established biofilms may provide a progressive alternative to standard methodology. Methods: We evaluated a novel technique of normal atmospheric nonthermal plasma known as floating-electrode dielectric-barrier discharge (FE-DBD) plasma against a control of planktonic and biofilm forms of Escherichia coli, S aureus, multidrug-resistant methicillin-resistant S aureus (MRSA) -95 (clinical isolate), -USA300, and -USA400, using widely accepted techniques such as colony count assay, LIVE/DEAD BacLight Bacterial Viability assay, and XTT (2,3-Bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay. Results: Exposure of free living planktonic forms of E coli, S aureus, and MRSA were rapidly inactivated by DBD plasma. Approximately 107 bacterial cells were completely (100%) killed, whereas 108 and 109 were reduced by approximately 90% to 95% and 40% to 45%, respectively, in less than 60 seconds (7.8 J/cm2) and completely disinfected in ≤120 seconds. In established biofilms, the susceptibility of MRSA USA400 was comparable with USA300 but less susceptible than MRSA95 (clinical isolate), S aureus, and E coli (P < .05) to FE-DBD plasma, and plasma was able to kill MRSA more than 60% within 15 seconds (1.95 J/cm2). The killing responses were plasma exposure-time dependent, and cell density dependent. The plasma was able disinfect surfaces in a less than 120 seconds. Conclusion: Application of DBD plasma can be a valuable decontamination technique for the removal of planktonic and biofilm-embedded bacteria such as MRSA -USA 300, -USA 400, methicillin-sensitive S aureus (MSSA), and E coli, the more common hospital contaminants. Of interest, E coli was more resistant than S aureus phenotypes.

The aim of this thesis was to elaborate the issue of the decomposition of volatile organic compounds in the Gliding Arc plasma discharge at atmospheric pressure. Technologies based on nonthermal plasma could offer a good alternative to conventional techniques for the decomposition of volatile organic compounds, such as thermal and catalytic oxidation. Gliding Arc discharge (GidArc) is a widely exploited nonthermal plasma source used for many industrial applications, such as air-pollution control. The energy efficiency, reaction selectivity or production of specific species may be achieved in this kind of plasma, and thus for various chemical processes it can be much more effective then in conventional techniques. Presented experiments are linked to the previous results published in diploma thesis, which gave us the basics for construction of new reactor and optical emission spectroscopy measurements have been done to characterize the plasma. Toluene (aromatic, unsaturated), cyclohexane (aromatic, saturated) and hexane (aliphatic, saturated) were used as the model compounds for these experiments in the concentration range from hundreds to thousands ppm. Results focused on the electrical parameters of the reactor were carried out, with the aim to operate the system at a lower energy cost. In order to get the time-resolved diagnostics of the moving plasma channel, the evolution of the plasma channel was recorded continuously by using a high-speed video camera. In next part of the work, some results concerning generation of low molecular products like nitric oxide, nitrogen dioxide, hydrogen and carbon monoxide on the discharge conditions are presented. In combustion process, undesirable mixture of toxic highmolecular by-products can be formed. Samples were therefore analysed in gas chromatograph linked to mass spectrometer, to characterize the chemical transformation pathway of VOC in plasma.

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Teilchenschauer können sowohl durch Photonen als auch durch geladene Teilchen erzeugt werden. Letztere kommen etwa 1000-mal häufiger vor als die durch Photonen erzeugten Teilchenschauer. Dies beeinflusst die Sensitivität des VERITAS-Experiments erheblich. Um diese gegenüber Gammastrahlung zu steigern, ist es notwendig, die Gamma-Hadron Separation zu verbessern. In dieser Dissertation wurde eine Analysemethode, basierend auf Boosted Decision Trees (BDTs), entwickelt und für die Analyse der Daten des VERITAS-Observatoriums optimiert. Das große Potential zur Unterscheidung von Teilchenschauern der Photonen und der Hadronen wird anhand ausführlicher Tests und systematischer Studien mit Simulationen von Gammastrahlung und Beobachtungsdaten der kosmischen Strahlung verdeutlicht. Im Vergleich zur Standardanalyse kann die Sensitivität mit Hilfe der BDT Methode deutlich erhöht werden. Die entwickelte und optimierte BDT Methode wird auf Beobachtungsdaten der Cygnus-Region angewandt. Diese ist eine der aktivsten sternbildenden Regionen unserer Galaxie und beherbergt eine Vielzahl von potentiellen kosmischen Teilchenbeschleunigern. Aufgrund der enormen Dichte an potentiellen Quellen sowie der hohen Wahrscheinlichkeit, neue Quellen zu detektieren und zu identifizieren, wurde die Cygnus-Region von April 2007 bis Juni 2012 mit VERITAS beobachtet. Die Beobachtungsdaten wurden mit einer für diese Himmelsregion optimierten Analysetechnik aufbereitet und ausgewertet. Vier Quellen hochenergetischer Gammastrahlung wurden detektiert: VER J2031+415, VER J2019+407, VER J2019+368 und VER J2016+371. Detaillierte spektrale Untersuchungen werden vorgestellt, gefolgt von einer Diskussion möglicher assoziierter Objekte in anderen Wellenlängenbereichen. Schließlich konnten mit Hilfe der verbesserten Sensitivität von VERITAS durch die BDT Methode niedrigere Obergrenzen für den Fluss der hochenergetischen Gammastrahlung von 50 potentiellen Gammastrahlungsquellen abgeleitet werden. / Particle showers can be generated by photons or charged cosmic rays. Before applying any selection requirements, showers initiated by cosmic rays are about 1000 times more common than those initiated by photons. This constitutes a vast amount of background events measured by VERITAS, limiting the sensitivity to gamma rays. To improve the separation power between gamma-ray and cosmic-ray showers, an analysis technique based on Boosted Decision Trees (BDTs) is developed. Extensive tests are performed to study the discrimination capabilities of the BDT method using cosmic-ray data and Monte-Carlo simulations of gamma rays. Compared to the VERITAS standard analysis, the BDT method improves the sensitivity of detecting gamma rays. The BDT method is applied to data obtained from observations of the Cygnus region, one of the most active star-forming regions of our Galaxy. It hosts numerous astrophysical objects capable of accelerating particles to extremely high energies, such as supernova remnants, pulsar wind nebula, binary systems, and associations of massive OB stars. The high density of potential sources and the information from multiwavelength observations led VERITAS to perform observations of the Cygnus region between April 2007 and June 2012. Four sources were detected in very-high-energy gamma rays: VER J2031+415, VER J2019+407, VER J2019+368, and VER J2016+371. They were analysed in detail and compared to possible counterparts measured at other wavelengths. The spectra of the three of the sources were fit to a power law. Two out of three spectra are consistent with those obtained in previous measurements, where the third one shows a softer spectral index than the published result. Finally, the greater sensitivity reached with the BDT method allowed the derivation of the most stringent upper limits to date on 50 potential gamma-ray sources.

Orientadores: Jayr de Amorim Filho, Marco Aurélio Pinheiro de Lima / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-08-24T21:57:52Z (GMT). No. of bitstreams: 1 Ridenti_MarcoAntonio_D.pdf: 6265448 bytes, checksum: 384897ffe1b8b10a23a0ab7c3b206b76 (MD5) Previous issue date: 2014 / Resumo: Neste trabalho plasmas não térmicos gerados em pressão atmosférica e sustentados por ondas de superfície em micro-ondas, tendo o argônio como gás de alimentação, foram estudados experimentalmente e teoricamente tendo em vista aspectos pouco compreendidos de suas propriedades físicas e aplicações voltadas ao tratamento de biomassa. Medições da composição elementar e dos parâmetros físicos foram realizados por meio de técnicas de diagnóstico baseadas em espectrometria de massa e espectroscopia óptica de emissão. O sistema físico foi modelado por meio das equações de continuidade das espécies neutras e carregadas, da equação do calor e da equação de Boltzmann dos elétrons, que foram acopladas utilizando um procedimento auto-consistente. Uma vez obtido o quadro geral das propriedades do plasma, foi estabelecida a condição de operação adequada ao tratamento das amostras derivadas de biomassa. O tratamento foi realizado sobre quatro tipo de amostras: lignina, xilana, celulose e bagaço de cana-de-açúcar. Dentre as contribuições importantes deste trabalho podem ser destacadas: (i) a verificação experimental do papel dos íons moleculares do argônio no processo de contração da descarga; (ii) a determinação do perfil axial no plasma dos principais íon positivos e negativos, da densidade e temperatura eletrônicas, da temperatura do gás e da densidade do estado metaestável Ar(1s5); (iii) verificação da seletividade do tratamento a plasma, tendo sido observada uma alteração significativa dos espectros de absorção no infravermelho nos casos da lignina e da xilana, mas não no caso da celulose. Esse último resultado sugere uma rota inusitada para novas tecnologias de deslignificação e síntese de novos materiais a partir de biomassa / Abstract: In this work non-thermal argon plasmas produced at atmospheric pressure and sustained by microwave surface waves were theoretically and experimentally studied in view of their non understood aspects and also the applications aimed at biomass treatment. Measurements of elemental composition and physical parameters were carried by means of plasma diagnostic techniques such as mass spectrometry and optical emission spectroscopy. Plasma modelling based on the self-consistent solution of the continuity equations of the neutral and charged species, the heat equation and the electron Boltzmann equation was developed to describe the plasma properties. Once a complete picture of the plasma behaviour was obtained, a promising condition for plasma treatment was established. Four types of biomass derived material were plasma treated: lignin, cellulose, xylan and sugarcane bagasse. Among the important contributions of this work one may highlight the following: (i) the experimental verification of the crucial role of argon molecular ions in the discharge contraction; (ii) axial profile determination of the main positive and negative ions, the electronic temperature and density, the gas temperature and the metastable state Ar(1s5) density; (iii) important modification of the infrared absorption spectra after plasma treatment in the cases of lignin and xylan, but not in the case of cellulose, suggesting a unexpected route for delignification and new materials synthesis from biomass / Doutorado / Física / Doutor em Ciências

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