Distonia focal é uma desordem neurológica do movimento que pode ser altamente incapacitante afetando de maneira importante a vida, carreira professional e práticas interpretativas dos músicos. Segundo pesquisas a distonia focal pode manifestar-se em até 1% dos músicos. O objetivo principal da presente pesquisa foi investigar as estratégias de estudo utilizadas por três músicos profissionais com distonia focal (dois flautistas e um violinista). Adicionalmente se realizou um auto relato, no qual o autor (que também sofre da doença) descreve e analisa seu processo, focalizando-se nos mesmos aspectos investigados nas entrevistas. Os resultados obtidos foram confrontados com a literatura sobre o tema, a experiência pessoal do autor e com as respostas proporcionadas por um músico, neurologista e especialista em distonia focal (por meio de uma outra entrevista). A coleta de dados dos participantes foi realizada através de entrevistas semiestruturadas. Os resultados obtidos apontam que o uso das estratégias de estudo é variado e individualizado conforme: as características particulares de cada caso, gravidade da doença, instrumento interpretado, o processo pessoal com a doença, as expectativas pessoais, etc. Porém, a pesquisa destaca a importância da terapia física para desenvolver novas habilidades motoras interpretativas e também a utilização de terapia psicológica para reduzir os níveis de ansiedade no estabelecimento de uma nova relação com o instrumento. Dentre as estratégias musicais encontradas para lidar com a doença estão: adequações no repertorio de estudo, práticas musicais paralelas e modificações no instrumento. / Focal dystonia is a neurological movement disorder that can be highly incapable, affecting life, professional career and music performing. According to studies, up to 1% of musicians can be affected. The principal objective of this research was to explore the study methodologies used by three professional musicians with focal dystonia. Additionally a selfreport developed by the author (who also is affected by disease) narrates and analyze his personal process focusing on the same aspects that are investigated in the interviews. Data was collected from participants using semi-structured interviews. The results were compared with academic publications, personal experience of the author and with answers given by a musician, neurologist and specialist in focal dystonia, (collected in another interview). Part of the data is the Self- report, where the author presents its personal process with focal dystonia, based on self-observation, motor re-learning and Alexander Technique. The results obtained highlighted that the use of methodological studies diverse and personalized, according to particular characteristics of each case (the state of the disease, the instrument played by the musician, the personal process, recovery expectations, etc.). However, in general, the following aspects were founded: physical therapy, for constructing new motor patterns and psychological therapy to reduce the levels of anxiety and begin to establish a new relationship with the instrument. Among musical methodologies to face disease the following are included: adjustments in the musical repertory, parallel musical practice and instrument modifications.

Distonia focal é uma desordem neurológica do movimento que pode ser altamente incapacitante afetando de maneira importante a vida, carreira professional e práticas interpretativas dos músicos. Segundo pesquisas a distonia focal pode manifestar-se em até 1% dos músicos. O objetivo principal da presente pesquisa foi investigar as estratégias de estudo utilizadas por três músicos profissionais com distonia focal (dois flautistas e um violinista). Adicionalmente se realizou um auto relato, no qual o autor (que também sofre da doença) descreve e analisa seu processo, focalizando-se nos mesmos aspectos investigados nas entrevistas. Os resultados obtidos foram confrontados com a literatura sobre o tema, a experiência pessoal do autor e com as respostas proporcionadas por um músico, neurologista e especialista em distonia focal (por meio de uma outra entrevista). A coleta de dados dos participantes foi realizada através de entrevistas semiestruturadas. Os resultados obtidos apontam que o uso das estratégias de estudo é variado e individualizado conforme: as características particulares de cada caso, gravidade da doença, instrumento interpretado, o processo pessoal com a doença, as expectativas pessoais, etc. Porém, a pesquisa destaca a importância da terapia física para desenvolver novas habilidades motoras interpretativas e também a utilização de terapia psicológica para reduzir os níveis de ansiedade no estabelecimento de uma nova relação com o instrumento. Dentre as estratégias musicais encontradas para lidar com a doença estão: adequações no repertorio de estudo, práticas musicais paralelas e modificações no instrumento. / Focal dystonia is a neurological movement disorder that can be highly incapable, affecting life, professional career and music performing. According to studies, up to 1% of musicians can be affected. The principal objective of this research was to explore the study methodologies used by three professional musicians with focal dystonia. Additionally a selfreport developed by the author (who also is affected by disease) narrates and analyze his personal process focusing on the same aspects that are investigated in the interviews. Data was collected from participants using semi-structured interviews. The results were compared with academic publications, personal experience of the author and with answers given by a musician, neurologist and specialist in focal dystonia, (collected in another interview). Part of the data is the Self- report, where the author presents its personal process with focal dystonia, based on self-observation, motor re-learning and Alexander Technique. The results obtained highlighted that the use of methodological studies diverse and personalized, according to particular characteristics of each case (the state of the disease, the instrument played by the musician, the personal process, recovery expectations, etc.). However, in general, the following aspects were founded: physical therapy, for constructing new motor patterns and psychological therapy to reduce the levels of anxiety and begin to establish a new relationship with the instrument. Among musical methodologies to face disease the following are included: adjustments in the musical repertory, parallel musical practice and instrument modifications.

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The Phase Induced Amplitude Apodization Complex Mask Coronagraph (PIAACMC) is an architecture for directly observing extrasolar planets, and can achieve performance near the theoretical limits for any direct-detection instrument. The PIAACMC architecture includes aspheric PIAA optics, and a complex phase-shifting focal plane mask that provides a pi phase shift to a portion of the on-axis starlight. The phase-shifted starlight is forced to interfere destructively with the un-shifted starlight, causing the starlight to be eliminated, and allowing a region for high-contrast imaging near the star. The PIAACMC architecture can be designed for segmented and obscured apertures, so it is particularly well suited for ground-based observing with the next generation of large telescopes. There will be unique scientific opportunities for directly observing Earth-like planets around nearby low-mass stars. We will discuss design strategies for adapting PIAACMC for the next generation of large ground-based telescopes, and present progress on the development of the focal plane mask technology. We also present simulations of wavefront control with PIAACMC, and suggest directions to apply the coronagraph architecture to future telescopes.

En la presente tesis se desarrolló el cálculo del mecanismo focal, usando el método de la polaridad de la onda P, para el sismo de Yauca del 2013 y el sismo de Coracora del 2014 y luego se comparará los resultados con los mecanismos focales obtenidos por el CMT y el USGS-NEIC; y con ello se determinará la precisión del cálculo del mecanismo focal con este método. El método de Primeras Polaridades de las Ondas P se empleó antes del desarrollo de los ordenadores y de la generalización de señales sísmicas de banda ancha, y aún se sigue utilizando, para analizar eventos sísmicos.Para emplear este método se trabajará con los sismogramas registrados por diferentes estaciones telesísmicas a nivel mundial y tratará de obtenerse la mayor cantidad de lecturas de polaridades, para que el error en el cálculo del mecanismo focal sea el menor posible. La solución del mecanismo focal será el resultado del análisis de las formas de ondas sísmicas generadas por el evento sísmico, registradas en una serie de estaciones sísmicas, mediante sismogramas de componente vertical. La caracterización precisa del mecanismo focal del evento nos proporciona información muy importante para los sismólogos y geólogos estructurales que trabajan en estructuras activas; ya que nos da el epicentro, la profundidad focal, la magnitud, así como la orientación del posible plano de falla y su movimiento. La importancia de esta tesis, es que resolviendo el mecanismo focal se podrá obtener la geometría del área de ruptura, y ello serviría para la prevención de desastres por fenómenos naturales; y estaría dirigido a las autoridades con poder de decisión, sobre una determinada región. También ayudaría para tomar decisiones al realizar obras de infraestructura civil, por ejemplo sea el caso de construir una represa; con la información del mecanismo focal, se podría caracterizar la orientación de la geometría de una falla pre-existente, y con ello se determinaría si es factible construir la represa en dicho lugar, o realizar algún otro tipo de construcción en aquella zona. Debido a la importancia del tema, se desarrolla la presente tesis, en donde a su vez se ha utilizado algoritmos computacionales, como el modelo numérico MECSTA, el cual fue muy útil al determinar el mecanismo focal de los eventos sísmicos mencionados.

Focal adhesions are dynamic multiprotein structures connecting cells to their surrounding microenvironment. Cells receive critical mechanical signals from adhesions that control many cellular processes including wound healing, differentiation, development, and cancer. Proteins that form adhesions are called adhesion proteins and some of these proteins can be mechanosensitive, meaning that they respond to mechanical stimuli. During spreading and migration, cells mechanically test extracellular matrix rigidity by contracting matrix to a constant displacement. Transmission and processing of such mechanical signals rely upon the dynamic regulation of the adhesions, which is tightly coordinated with activation of intracellular signaling cascades involving various adhesion molecules. However, the molecular mechanisms of mechanical signals that are transmitted through the adhesions to control cell behavior are poorly understood. In this thesis, we discovered novel phenomenon and mechanisms to elucidate roles of mechanical signals for multiple key aspects of basic cell behavior, especially cell growth. We performed live cell imaging of cells spreading on fibronectin coated micropillars to understand adhesion formation, adhesion regulation, and their impact on cell behavior. One of the earliest molecules to arrive at an adhesion formation site is a mechanosensitive protein called talin which binds to several other entities to form the backbone of focal adhesions. We found a novel role of talin cleavage, which previously was thought to play a role only in focal adhesion turnover. We found that talin cleavage is a force dependent process that regulates proper adhesion formation, thereby governing several critical cellular processes. In the absence of this talin cleavage, cells formed abnormal adhesions and showed inhibited growth. Further, we found that upon inhibition of talin cleavage, one of the key cellular behaviors of increased cellular motility upon stimulation by epidermal growth factor seemed to disappear. Epidermal growth factor receptor is a transmembrane protein and has previously been shown to play important role in various cancers where cells exhibit altered rigidity sensing. Surprisingly, we found that epidermal growth factor receptor was required for cellular rigidity sensing only on rigid substrates, highlighting the importance of the interplay between mechanical and biochemical signals in determining cell behavior.

This research used qualitative methods to investigate the police officer decision-making processes within the theoretical context of the focal concerns framework and the theory of planned behavior. This research had two primary goals. The first goal was to determine what similarities and differences exist in how ideas from the focal concerns framework manifest themselves in a policing context as compared to how they operate for judges when sentencing convicted offenders. The second goal of this research was to use ideas from the theory of planned behavior to elaborate the focal concerns framework into a functional theoretical model of police officer decision-making. While intuitively sound, the focal concerns perspective is in need of conceptual enhancements to operationalize the mechanisms through which the focal concerns identified are transformed into action. Interviews with police officers were conducted to elicit the considerations that police officers see as important to their decision-making process in order to develop a theory of police decision-making which incorporates concepts from the focal concerns framework and the theory of planned behavior. The results of this study indicate that although police officers share the same broad focal concerns as judges, the way these concerns manifest themselves in the execution of their duties is different for police officers. The results also indicate that the construct of intent from the theory of planned behavior may be a viable cognitive mechanism to connect ideas from the focal concerns framework with criminal justice outcomes, although other constructs from the theory were only found to be partially applicable. Theoretical implications of the findings and directions for future research are also discussed.

It is estimated that more than 60% of cancer patients will receive radiotherapy (RT). Medical images acquired from different imaging modalities are used to guide the entire RT process from the initial treatment plan to fractionated radiation delivery. Accurate identification of the gross tumor volume (GTV) on computed tomography (CT), acquired at different time points, is crucial for the success of RT. In addition, complementary information from magnetic resonance imaging (MRI), positron emission tomography (PET), cone-beam computed tomography (CBCT) and electronic portal imaging device (EPID) is often used to obtain better definition of the target, track disease progression and update the radiotherapy plan. However, identifying tumor volumes on medical image data requires significant clinical experience and is extremely time consuming. Computer-based methods have the potential to assist with this task and improve radiotherapy. In this thesis a method was developed for automatically identifying the tumor volume on medical images. The method consists of three main parts: (1) a novel rigid image registration method based on scale invariant feature transform (SIFT) and mutual information (MI); (2) a non-rigid registration (deformable registration) method based on the cubic B-spline and a novel similarity function; (3) a gradient-based level set method that used the registered information as prior knowledge for further segmentation to detect changes in the patient from disease progression or regression and to account for the time difference between image acquisition. Validation was carried out by a clinician and by using objective methods that measure the similarity between the anatomy defined by a clinician and by the method proposed. With this automatic approach it was possible to identify the tumor volume on different images acquired at different time points in the radiotherapy workflow. Specifically, for lung cancer a mean error of 3.9% was found; clinically acceptable results were found for 12 of the 14 prostate cancer cases; and a similarity of 84.44% was achieved for the nasal cancer data. This framework has the potential ability to track the shape variation of tumor volumes over time, and in response to radiotherapy, and could therefore, with more validation, be used for adaptive radiotherapy.

Although clemency is often an offender's final prospect to avoid execution within the death penalty context, prior research concerning clemency decisions remains limited by the fact that it is often atheoretical and researchers have used data more than a decade old. This study specifically placed clemency decisions within a focal concerns framework and examined death row inmates who were either executed or granted clemency between 1984 and 2008. This study used logistic regression as its primary modeling technique to examine whether measures of focal concerns theory were predictive of clemency decisions. While the current measures for offender blameworthiness and protection of the community were not found to influence clemency decisions, practical constraints and consequences measured by political factors and regional location along with offender characteristics were found to predict such decisions. Female offenders, non-white offenders, and offenders with lower educational levels were most likely to be granted clemency. Whereas lame duck governors were more likely to grant clemency, governors in southern states were less likely to grant clemency. The odds of clemency were reduced with each year an offender served.

Tese (doutorado)—Universidade de Brasília, Instituto de Química, Programa de Pós-Graduação em Química, 2013. / Submitted by Alaíde Gonçalves dos Santos (alaide@unb.br) on 2014-01-10T10:55:15Z No. of bitstreams: 1 2013_DanielAugustoBarradeOliveira.pdf: 2428120 bytes, checksum: c456b5418b233575e486a336a32f5cb7 (MD5) / Approved for entry into archive by Guimaraes Jacqueline(jacqueline.guimaraes@bce.unb.br) on 2014-02-17T13:52:04Z (GMT) No. of bitstreams: 1 2013_DanielAugustoBarradeOliveira.pdf: 2428120 bytes, checksum: c456b5418b233575e486a336a32f5cb7 (MD5) / Made available in DSpace on 2014-02-17T13:52:04Z (GMT). No. of bitstreams: 1 2013_DanielAugustoBarradeOliveira.pdf: 2428120 bytes, checksum: c456b5418b233575e486a336a32f5cb7 (MD5) / As proteínas quinases são importantes por atuar em processos biológicos conhecidos, como a transdução de sinais. Esses processos estão intimamente relacionados com o desenvolvimento de neoplasias malignas. Desse modo, o conhecimento da atuação de drogas, relacionadas com essas proteínas, é relavante para o tratamento de alguns tipos de câncer. Neste trabalho, procurou-se estudar inibidores da proteína quinase de adesão focal (FAK), a fim de correlacionar propriedades teóricas, obtidas pela química computacional, com atividades biológicas calculadas a partir do IC50, para auxiliar no entendimento entre essas drogas e a FAK. Para realizar os cálculos foram usadas diversas aproximações de modelagem molecular, dentre as quais, mecânica molecular, métodos ab initio, e métodos híbridos. Para a aproximação de mecânica quântica foram usados os métodos Hartree-Fock, teoria do funcional de densidade, e semi-empíricos PM3, PM6 e MNDO, para descrever a interação entre o sítio catalítico da FAK e os inibidores. O programa O programa auto-docking Vina foi usado para o ancoramento rígido. As atividades de inibidores da classe 7-h-pirrolo-pirimidina foram comparadas com dados provenientes da mecânica quântica, cujo resultado mostrou a importância dos orbitais de fronteira próximos ao aminoácido Cys502. Quanto mais estendidos esses orbitais, maior poderá ser atividade de inibição da FAK. São ainda observadas interações moleculares com os aminoácidos Arg424 e Lys454. Os inibidores dasatinib, sulfonamida e tiazole também foram estudados com métodos de química quântica. Esses inibidores mostram tendências químicas semelhantes com aqueles da classe pirrolo pirimidina, no que se refere às interações com os aminoácidos da tríade catalítica, enfatizando a necessidade dessas interações na construção de novos inibidores. Além disso, a partir da análise de componentes principais, foi mostrada uma correlação entre atividades e propriedades eletrônicas. A soma de todos esses estudos leva a novas fronteiras para o entendimento da interação de fármacos inibidores da proteína quinase e, consequentemente, a compreensão da inibição da metástase, que são uma das maiores causas de morte no mundo moderno. _______________________________________________________________________________________ ABSTRACT / The kinases proteins play important role acting in known biological process, as the signal transduction. These processes are strongly related to the development of malignant neoplasms. Therefore, the knowledge of the drug action related to the kinase protein is relevant for the cancer treatment. In this work, it was studied inhibitors of focal adhesion kinase (FAK) protein in order to correlate theoretical properties with biological activity via IC50, to understand the interaction between these drugs with FAK. In order to perform the calculations it was employed several approaches of molecular modeling, as molecular mechanics, ab initio and hybrid methods. For the quantum mechanical approach we have used Hartree-Fock, density functional theory and semi-empirical PM3, PM6, MNDO methods to describe the interaction between the catalytic site of FAK binding and the selected inhibitors. Auto Docking Vina program was employed to perform the rigid docking. The inhibitor activities of 7-h-pirrole-pirimidines were compared to the results of quantum mechanical approaches, and these results shows the important relation to the frontier orbitals close to the Cys502 aminoacid. The largest contribution of these orbitals is closely related to the FAK inhibition. The molecular interaction with Arg454 and Lys454 aminoacids were also showed. Dasatinib, sulfonamide and thiazole inhibitors also presents these main interactions, emphasizing the relevance of catalytic site interaction of FAK with new inhibitors. Furthermore, from the principal component analysis, it was shown a correlation between activity and electronic properties. The present study leads to new frontiers for the understanding the interaction between focal adhesion kinase and the inhibitors, which is related to the metastase, one o the main reason of death in the world.