Made available in DSpace on 2018-08-01T23:26:05Z (GMT). No. of bitstreams: 1 tese_12037_Ata Defesa Carolina Brioschi.pdf: 381703 bytes, checksum: b4f595f3f87e31065e1ee0930dc4873d (MD5) Previous issue date: 2018-04-20 / Introdução: A articulação temporomandibular (ATM) pode ser afetada pelos mesmos processos patológicos de outras articulações do organismo. A osteoartrite (OA) é a desordem de origem articular que mais acomete a ATM e é caracterizada pela degeneração dos tecidos ao seu redor. A OA possui etiologia complexa e a má oclusão é considerada um fator de risco por criar áreas de trauma na cartilagem articular da mandíbula, aumentando a produção de enzimas que degradam a cartilagem, como as agrecanases e metaloproteinases (MMPs), que são por sua vez reguladas por seus inibidores teciduais (TIMPs). Dentre os 4 tipos de TIMPs existentes, a TIMP-1 é a mais importante pois além de reguladora tecidual das MMPs, desempenha papel de molécula sinalizadora em processos biológicos importantes. Objetivo: Investigar as respostas da cartilagem articular da mandíbula (CAM) diante de má oclusão experimental e avaliar as mudanças na expressão de TIMP-1. Métodos: Foram utilizadas 24 fêmeas de ratos Wistar com 8 semanas de vida divididas em grupo controle e tratado, com dois tempos experimentais (2 e 4 semanas). Os animais foram submetidos à uma desordem oclusal sagital através da movimentação mesial dos primeiros molares e distalização dos terceiros unilateralmente e em lados opostos das arcadas. Ao final de 2 e 4 semanas, as alterações morfológicas na CAM foram avaliadas. A expressão de TIMP-1 foi detectada por técnica imuno-histoquímica. As análises quantitativas foram feitas através de software de imagem e passaram por análise estatística sendo considerados significantes os resultados com valor de P menores que 0.05. Resultados: Animais tratados por 2 e 4 semanas apresentaram alterações degenerativas na CAM características de OA. Os principais achados foram espessamento do terço posterior, desarranjo das camadas, atividade osteoclástica e formação de osteófito. Entre os aspectos celulares, presença de condrócitos com núcleo condensado e redução do citoplasma foram observados. A expressão de TIMP-1 nos animais controle foi observada apenas na camada madura. Já nos tratados, células imunopositivas foram encontradas nas camadas proliferativa e madura, sendo que nos animais tratados por 2 semanas o terço posterior apresentou maior número de células imunomarcadas do que o grupo controle (P= 0.0291). Conclusão: O estudo demonstrou que uma desordem oclusal pode levar a respostas degenerativas na CAM acompanhadas de alterações na expressão de TIMP-1.

Brain Machine Interfaces (BMI) provide a communication pathway between the electrical conducting units of the brain (neurons) and external devices. BMI technology may provide improved neurological and physiological functions to patients suffering from disabilities due to damaged nervous systems. Unfortunately, microelectrodes used in Intracortical Neural Interfaces (INI), a subset of the BMI device family, have yet to demonstrate long-term in vivo performance due to material, mechanical and electrical failures. Many state-of-the-art INI devices are constructed using stacks of multiple materials, such as silicon (Si), titanium (Ti), platinum (Pt), parylene C, and polyimide. Not only must each material tolerate the biological environment without exacerbating the inflammatory response, each of the materials used must physically withstand the environment as well as interact well with each other. One approach to address abiotic mechanisms has been optimizing the materials required to fabricate the INI devices. Silicon Carbide (SiC) is a physically robust, hemo and biocompatible, and chemically inert semiconductor. An ‘all-SiC’, or monolithic SiC, device may be the disruptive technology needed in the BMI field to finally achieve long-term and wide-spread use of this technology in humans. The all-SiC device concept is where SiC serves as all device layers: the base (substrate), the conducting traces (electrodes), and the surface conformal insulating layer. The monolithic SiC neural probe is realized by forming high-quality pn junctions of heavily doped SiC on a layer of the opposite polarity. Heavily doped semiconductors display semi-metallic electrical performance, which allow for efficient electrical conduction in the electrode without the deleterious effects of metal ions interacting with the neural environment. The conformal insulator is realized using amorphous-SiC (a-SiC) which can be patterned to open windows to allow electrical conduction to occur between the electrode tips and the brain. Several generations of monolithic SiC devices have been fabricated, tested and are reported in this dissertation. The devices were fabricated utilizing two polytypes of SiC (4H-SiC and 3C-SiC). The monolithic SiC microelectrodes were fabricated utilizing techniques used in the fabrication of Si based microelectrodes. Monolithic SiC devices fabricated include planar single-ended MEAs (with varying lengths and varying active recording area), 60-channel MEAs for in-vitro studies, and 16-electrode Michigan style neural probes for in-vivo studies. Electrical testing of the pn junction demonstrated that the 4H-SiC device can block a forward bias voltage of up to 2.3V and displays reverse bias leakage below 1 nArms well past -20V. Current leakage between adjacent electrodes was ~7.5 nArms over a voltage range of -50V to +50V. Furthermore, electrochemical results show that the 4H-SiC microelectrodes interact with an electrochemical environment primarily through capacitive mechanisms and has an impedance comparable to gold electrodes. Electrode impedance ranged from 675±130 kΩ (GSA = 496 µm2) to 46.5±4.80 kΩ (GSA = 500K µm2). However, the 4H-SiC devices cannot deliver charge as efficiently as other conventionally used microelectrode materials, such as iridium oxide (IrOx), but a larger water window compensates for this since larger stimulation voltages are supported compared to IrOx. All studies and data collected thus far indicate that the monolithic SiC neural device can aid in the advancement of chronic INI use in clinical settings. The all-SiC devices rely on the integration of only robust and highly compatible SiC material, they may offer a promising solution to probe delamination and biological rejection associated with the use of multiple materials used in many current INI devices. Follow-on work is planned to prove this assertion via in vivo studies.

It would be of great value to have a precise and non-damaging neuromodulation technique in the field of basic neuroscience research and for clinical treatment of neurological diseases. Infrared neural modulation (INM) is a new modulation modality developed in the last decade, which uses pulsed or continues infrared (IR) light with a wavelength of 1200 to 2200 nm to directly alter neural signals. INM includes both infrared neural stimulation (INS) and infrared neural inhibition (INI). INM is widely investigated for use on peripheral nerves, cochlear nerve fibers, cardiac cells, and the central nervous system. This technique holds the advantages of contact-free and high spatiotemporal precision compared to the traditional electrical stimulation. It does not depend on genetic modification and exogenous absorbers as other optical techniques, such as the optogenetic technique and the enhanced near-infrared neural stimulation (e-NIR). These advantages make INM a viable technique for research and clinical applications. The primary mechanism of the INM is believed to be a photothermal effect, where the IR laser energy absorbed by water leads to a rapid local temperature change. However, so far the details of the mechanism of action potential (AP) generation and inhibition remain elusive. Another issueis that the cells may be endangeredbythe heat exposure, consequently triggering a physiologicalmalfunction or even permanent damage.These concernshave hindered the transfer of the INM technique to the clinical therapy.Therefore, the general aim of this study was to improve the understanding of the details of how INM affects the cells. Laser parameters for safe and efficient stimulation were investigated on the basis of being useful for clinical applications. A tailored heating model and in vitro INM experiments on cortex neurons were used to reach this goal.The first paper was a feasibility study. A 1550nm laser with a beam spot diameter of around 6 mm was used to irradiate the rat cortex neurons, which were seeded on multi-electrode arrays (MEA) and formed well-connected networks. A heating model based on an estimated laser beam (standard Gaussian distribution) was used to simulate temperaturechanges. The damage signal ratio (DSR),based on the temperature,was calculated to predict the heat damage. The average spike rate of all the working electrodes from two MEAs was used to evaluate the degree of theinhibition of the neural networks. Results IVshowed that it is possible to use the 1550 nm laser to safely inhibit the neural network activity and that the degree of the INI is dependent on the power of the laser.The second paper wasan application and mechanism study. The aim of this study was to investigate the safety, efficiency, and cellular mechanism of INI. The same laser as in paper Iwas used in this study. A 20 X objective was used to decrease the beam spot diameteraround 240 μm. The measured laser profile (high order Gaussian beam) was used in the heating model to predict the temperature. The model was verified by local temperature measurements viamicropipette. The action potential rates, measured by the MEA electrodes, were quantified for different temperatures. Bicuculline was added to the cortex neuron cultures to induce hyperexcitation of the neural network. The results showed that the INI is temperature dependent and that the temperature needs to be less than 46 °C at 30 s laser irradiation for safe inhibition. The IR laser couldalso be used to inhibit the hyperexcitedactivity. The degree of inhibition, for the assessed subpopulation of neurons, was better correlated with the action potential amplitude than the width of it and INIcan be accomplished without inhibitory synapses / <p>QC 20180920</p><p></p>

Understanding and working with Microsoft Windows registry is an important ability from the perspective of security. This ability is used by malicious software as well as by software, which repaires the damage caused by activity of malicious software. However, applications accessing and working with the registry are platform dependent, which may not always be convenient and it can lead to other problems if the platform is not secure. Therefore, the aim of this work is to create a platform independent application for accessing and working with registry, which makes possible to analyse the effect of malware on registry.

La tesis estudia la evolución del parque de generación de energía eléctrica durante el franquismo (1940-1975). En este período comenzó la formación de un sistema unificado de explotación, y durante su desarrollo se pasó de 1.731Mw a 25.467Mw. El sistema que se denominó “autorregulación”, permitió la coexistencia de las empresas eléctricas privadas, agrupadas alrededor de UNESA y el INI en su vertiente eléctrica. Sin embargo, las decisiones y la política eléctrica, y más tarde energética, estuvo directamente influida por el gobierno. Se analiza la importancia de las fuentes (hidráulica, carbón, fuel oil, gas natura, nuclear) de energía primaria en la generación de energía eléctrica. Asimismo, se estudia, aunque no de manera exhaustiva el impacto del medio ambiente y sus consecuencias y efectos a largo plazo. Todo ello se desarrolla en el contexto histórico pertinente bajo una vertiente técnico-económica. / The thesis studies the evolution of the power generation system of electricity, during the Franco’s Regime (1940-1975). In this period, it began the construction of a unified system of exploitation, where the power installed was moved from 1.731Mw to 25.467Mw. The system was called "self regulation", allowing the coexistence of private electric companies, grouped around UNESA and the INI in its electrical aspect. However, the decisions and the power policy, and later on the energy, was directly influenced by the government. It discusses the importance of the primary energy sources (hydro, coal, fuel oil, natural gas, nuclear) in electric power generation. However, it is not intended to illustrate a comprenhensive explanation of the environmental impact and its consequences and effects long term. To sum up, all this takes place in the relevant historical context in a technical and economical perspective.