3 Title: Moment-tensor inversion of earthquakes in Greece, method ISOLA Author: Dana Červinková Department: Department of Geophysics Supervisor: Prof. RNDr. Jiří Zahradník, DrSc. Supervisor's e-mail address: jz@karel.troja.mff.cuni.cz Abstract: The possibility of obtaining a reliable moment tensor using a low-frequency waveform inversion from a single seismic station is studied. Deviatoric part of the moment tensor is described in usual way, using its orientation (angles strike, dip, rake), scalar seismic moment M0 and the double-couple percentage (DC%), and also by means of the coefficients of linear combination of elementary mechanisms. We estimate the formal error of the coefficients and study conditionality of the inverse problem. Data from earthquakes Trichonis (Mw = 5.2, April 2007) and Leonidio (Mw = 6.2, January 2008), Greece, are processed using software ISOLA (Sokos and Zahradník). The moment tensor is calculated from many stations and its stability is tested. This reference solution is compared to those independently obtained from single stations. Synthetic tests are performed to understand why the single-station estimates are sufficient for Trichonis, but not for Leonidio, paying attention to the focal depth, station azimuth and epicentral distance. It is found that the depth is crucial at...

1 Abstract Title: Consequences of experimentally induced perinatal cerebral ischemic lesion. Aim: This thesis aims to present the issues and analyze current knowledge in the field of perinatal brain damage, particularly perinatal cerebral ischemic lesions as the most common brain infarction in children. Basic characteristics of the disease, syndromology, pathophysiological mechanisms and risk factors are emphasized. Following the theoretical background the thesis analyzes current trends as well as the limitations of the diagnostics and therapy. The aim is to highlight the need for early diagnosis and emphasize the potential of preventive treatment strategies. The practical part follows the theoretical background and expands the topic on the analysis of motor and behavioral consequences of experimentally induced perinatal ischemic stroke. Method: Cerebral focal ischemia was induced experimentally by photothrombotic method to seven days old rats. Rose Bengal intravenously followed by continual illumination of the senzorimotor cortex using a green laser beam for 10 minutes was induced platelet aggregation and subsequent thrombosis. Eight animals at age of two months were evaluated for 7 days via observational cages PhenoTyper. Results: The theoretical part collected and processed theoretical data on the...

Objetivo: As relações sociais são importantes em diversas condições crônicas, com impacto nos resultados terapêuticos. Neste estudo nós relatamos as percepções de mulheres com endometriose e dor pélvica crônica sobre as suas interações sociais. Métodos: Foi realizado um estudo qualitativo sobre 29 mulheres com endometriose e dor pélvica crônica. O estudo foi realizado em um hospital universitário, localizado no sudeste do Brasil, entre fevereiro de 2013 e janeiro de 2014. As mulheres foram divididas em seis grupos focais. As transcrições das entrevistas foram analisadas, segundo a abordagem da teoria fundamentada, e enviadas as categorias emergentes, que foram codificadas utilizando a plataforma WebQDA. Resultados: O isolamento social foi o principal tema emergente. O isolamento social foi percebido como associado à falta de compreensão sobre sintomas de endometriose, à resignação diante dos episódios recorrentes de dor. Evitar a intimidade parceiro, isolamento da família e isolamento dos amigos foram às subcategorias identificadas. Conclusão: Nosso estudo fornece evidências que mulheres com endometriose desenvolvem isolamento social progressivo após o início da dor pélvica crônica. Este achado é importante para a abordagem multidisciplinar da doença / Objective: Social ties have been associated with outcomes of several chronic conditions. In this study we report perceptions of women with endometriosis and chronic pelvic pain about their social interactions. Methods: We conducted a qualitative study on 29 women with chronic pelvic pain and endometriosis. The study was conducted in a university hospital, localized in the southwest of Brazil, between February 2013 and January 2014. Women were enrolled in six focus groups interviews. Transcripts were analysed according to the grounded theory approach and the emerging categories were coded using the WebQDA platform. Results: Social isolation was the main emerging theme. Social isolation was perceived as associated with lack of understanding about endometriosis symptoms, and with resignation in face of recurrent pain episodes. Avoiding partner intimacy, isolation from family and isolation from friends were components of social isolation. Conclusion: Our study provides evidence that women with endometriosis develop progressive social isolation after the onset of chronic pelvic pain. This finding is important for the multidisciplinary management of the disease

O processo de treinamento e desenvolvimento de recursos humanos é um importante instrumento para a gerência e para a assistência, os estudos encontrados acerca do treinamento em Unidade de Terapia Intensiva (UTI) estão relacionados, principalmente, à realização de técnicas assistenciais. Reconhecendo a relevância do preparo do enfermeiro para atuação em UTI e sabendo da valorização que o grupo de enfermeiros da UTI de um hospital privado do município de São Paulo atribui ao processo de treinamento admissional, esta pesquisa foi desenvolvida na Instituição, Hospital Campo de Estudo (HCE). Assim, constituíram-se como objetivos desse estudo: analisar o processo de treinamento admissional do enfermeiro na UTI, na perspectiva dos enfermeiros da UTI do HCE; reelaborar o processo de treinamento admissional de enfermeiro na UTI, na perspectiva dos enfermeiros da UTI do HCE e definir o perfil do enfermeiro instrutor do treinamento admissional do enfermeiro. A fim de alicerçar essa reelaboração nos valores e necessidades expressas por esse grupo, optou-se pelo método de investigação, da pesquisa-ação. A técnica de coleta de dados ocorreu por meio de grupo focal, constituído de 11 enfermeiros com mais de três anos nessa UTI. Foram realizadas seis reuniões, totalizando dez horas de trabalho. Ainda, na coleta de dados, foram divulgados os relatórios-síntese dessas reuniões possibilitando a participação dos demais 18 enfermeiros da UTI que responderam aos questionários dirigidos, desse modo, houve contribuição de todo o coletivo estudado. Essa estratégia possibilitou a concretização da tarefa do grupo para além da proposta inicial de reelaboração do processo de treinamento. Em consonância ao perfil desejado para o enfermeiro dessa UTI, ora estabelecido pelo grupo, foram também descritos o conceito, os objetivos, as estratégias, a duração e as metas a serem alcançadas pelo enfermeiro recém-admitido. Para tal, foram construídos o novo instrumento, o fluxograma, o memento e a descrição do perfil do enfermeiro instrutor. Além do trabalho desenvolvido, a pesquisa promoveu no grupo e na pesquisadora a reflexão sobre aspectos intervenientes ao processo educativo, bem como acerca da identidade do grupo caracterizada pelo papel assistencial, pela autonomia de ação e, conseqüente, reconhecimento junto à equipe multiprofissional, o que facilitou, de modo coerente, a reelaboração do processo de treinamento admissional do enfermeiro da UTI-HCE / The human resource training and development process is an important instrument for management and care-providers. Studies regarding Intensive Care Unit (ICU) training relate especially to the performance of care-providing techniques. This research was developed at a Study Field Hospital (SFH) considering the importance of a nurses training process for performing at an ICU and knowing how ICU nursing staff value the admission training process at a private practice hospital in the city of São Paulo. Study objectives were to: analyze the ICU-nurse admission training process from the SFH ICU nurses standpoint; redesign the ICU-nurse admission training process from the SFH ICU nurses standpoint; and determine the educator-nurse profile for the ICU-nurse admission training process. In order to support this redesigning within the values and needs expressed by the group, the investigational method of action research was adopted. The data collection technique performed was based on a focus group composed of 11 nurses who have worked at this SFH ICU for more than three years. Six meetings were held in a total of ten working hours. Furthermore, during data collection, summarized meeting reports were issued allowing 18 other ICU nurses who answered the guided questionnaires to participate and therefore the whole group under study contributed. This strategy warranted concretization of the groups task further than the initially proposed redesigning of the training process. In agreement with the desired nurse profile for the ICU, now established by the group; concept, objectives, strategies, duration, and goals to be met by a recently-hired nurse were also described. For such, a new instrument, flow-chart, guideline and educator-nurse profile description were conceived. In addition to the work developed, this research fostered both in the group and the investigator a reflection on intervening aspects of the educational process as well as of the group identity, characterized by the care-providing role, autonomy to act and consequent recognition by the multi-professional team which coherently facilitated the redesigning of the nurse admission training process at the SFH ICU

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-03-26T16:55:48Z No. of bitstreams: 1 RODRIGO_BRACCINI_MADEIRA_DA_SILVA_TES.pdf: 6388000 bytes, checksum: c5e864eb62bd553c3a29e7bad1b85fef (MD5) / Rejected by Tatiana Lopes (tatiana.lopes@pucrs.br), reason: Devolvido porque o pdf inserido no TEDE ? de outro aluno. on 2018-03-28T14:20:43Z (GMT) / Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-03-28T14:24:15Z No. of bitstreams: 1 FERNANDA_MAJOLO_TES.pdf: 6002507 bytes, checksum: 764acb66fc06c518428a40b9eb5bdd26 (MD5) / Approved for entry into archive by Tatiana Lopes (tatiana.lopes@pucrs.br) on 2018-03-28T16:23:42Z (GMT) No. of bitstreams: 1 FERNANDA_MAJOLO_TES.pdf: 6002507 bytes, checksum: 764acb66fc06c518428a40b9eb5bdd26 (MD5) / Made available in DSpace on 2018-03-28T16:29:23Z (GMT). No. of bitstreams: 1 FERNANDA_MAJOLO_TES.pdf: 6002507 bytes, checksum: 764acb66fc06c518428a40b9eb5bdd26 (MD5) Previous issue date: 2018-01-11 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Malformations of cortical development (MDC) include a wide spectrum of Central Nervous System (CNS) disorders related to a complex process of cortex formation. Focal Cortical Dysplasia (FCD), a common type of MDC, is reported as the most frequent structural brain lesion found in children with refractory epilepsy to drug treatment undergoing surgery. Surgical treatment, with complete resection of the dysplastic lesion, is able to stop the seizure resistant to antiepileptic drugs, improving the individual's quality of life and reducing morbidity. FCD is characterized by multiple types of alterations both in cortical architecture and in cytologic abnormalities and it?s pathogenesis is still unknown. In 2004, Palmini et al. classified DCF according to white matter and cortical layer architecture. Taylor-type FCD is characterized by cortical laminar disorganization and dysplastic neurons, compromising the organization of the cortex into six-layered traditionally known. Understanding the mechanisms of action of neurological diseases has involved the use of animal models. However, in the case of brain development of epileptic syndromes, many decades of study have failed to provide a conclusive insight of their mechanisms. Modeling neurological diseases is especially attractive for the application of induced pluripotent stem cells (iPSCs), making possible to derive specific neurons for in vitro studies, contributing to the investigation of the disease. The aim of the present study was to investigate the possible differences in neurogenesis and neurodifferentiation of iPSCs from fibroblasts of individuals affected by Taylor-type FCD and normal individuals. iPSCs were generated from skin fibroblasts of two FCD individuals and two healthy individuals, to form the control group. The reprogramming was done through the fibroblasts exposure to viral vectors containing the OCT4, KLF4, SOX2, and c-MYC genes and the clones were characterized by immunohistochemistry. iPSCs were neurodifferentiated and analyzed at the 14th, 22nd and 35th days. We also analyzed the brain tissue, fibroblasts and iPSCs cells from the individuals. Through qRT-PCR, the expression of 14 genes involved in the neurodifferentiation process were quantified. These genes are associated to neural migration and differentiation, synaptic aspects and Notch signaling. Both individuals were diagnosed with Taylor-type FCD, more specifically, type IIb. In general, individuals with dysplasia presented alterations in the relative quantification in the most genes analyzed compared to control individuals in all processes and study groups (fibroblasts, brain tissue, iPSCs 8 and neurodifferentiated cells). The genes involved in the neural migration and differentiation processes, as well as synaptic aspects and Notch signaling presented quite altered expressions in dysplastic individuals, with the beginning of the majority processes early, before the physiologically typical period. From the found results, we can infer that during the embryonic period, in the neurogenesis and neurodifferentiation process, individuals affected by the disease, possibly presents neuroblasts more sensitive to stimulus, presenting differences in the development of the Nervous System. These changes may be directly related to dysplastic brain development. This work extends the understanding of embryonic neurodevelopment, open up opportunities to further investigations of the involvement and influence of each genes analyzed in the pathogenesis of FCD, as well as in each mechanism of action involved in the brain development. / As Malforma??es do Desenvolvimento Cortical (MDC) re?nem uma ampla gama de patologias do Sistema Nervoso Central (SNC) relacionadas a um complexo processo de forma??o do c?rtex. A Displasia Cortical Focal (DCF), tipo comum de MDC, ? relatada como a les?o cerebral estrutural mais frequente encontrada em crian?as com epilepsia refrat?ria ao tratamento medicamentoso submetidas ? cirurgia. O tratamento cir?rgico, com a ressec??o completa da les?o displ?sica, ? capaz de cessar a convuls?o resistente a drogas antiepil?ticas, melhorando a qualidade de vida do indiv?duo e diminuindo a morbidade. A DCF ? caracterizada por m?ltiplos tipos de altera??es tanto na arquitetura cortical quanto em anormalidades citol?gicas e sua patog?nese ainda ? desconhecida. Em 2004, Palmini e colaboradores classificaram as DCF de acordo com observa??es na subst?ncia branca e na arquitetura da camada cortical. A DCF do tipo Taylor ? caracterizada por uma desorganiza??o laminar e neur?nios displ?sicos, comprometendo a organiza??o do c?rtex em seis camadas histol?gicas tradicionalmente conhecidas. A compreens?o dos mecanismos de a??o das doen?as neurol?gicas tem envolvido o uso de modelos animais. Por?m, no caso do desenvolvimento cerebral das s?ndromes epil?pticas muitas d?cadas de estudo n?o conseguiram fornecer uma vis?o conclusiva sobre seus mecanismos. Modelar doen?as neurol?gicas ? especialmente atraente para aplica??o das c?lulas pluripotentes induzidas (iPSCs), possibilitando derivar neur?nios espec?ficos do pr?prio paciente para estudos in vitro, contribuindo para a investiga??o da doen?a. O objetivo do presente estudo foi investigar as poss?veis diferen?as na neurog?nese e neurodiferencia??o de iPSCs a partir de fibroblastos de indiv?duos acometidos pela DCF do tipo Taylor e indiv?duos normais. As iPSCs foram geradas a partir de fibroblastos de pele de dois indiv?duos displ?sicos e dois indiv?duos saud?veis, para compor o grupo controle. A reprograma??o se deu atrav?s da exposi??o dos fibroblastos a vetores virais contendo os genes OCT4, KLF4, SOX2, e c-MYC e os clones gerados foram caracterizados por imunohistoqu?mica. As c?lulas iPSCs foram neurodiferenciadas e analisadas nos per?odos de 14, 22 e 35 dias. Tamb?m foram analisados o tecido cerebral, fibroblastos e c?lulas iPSCs dos indiv?duos. Atrav?s de qRT-PCR, a express?o de 14 genes envolvidos no processo de neurodiferencia??o foram quantificados. Estes genes est?o associados a migra??o e diferencia??o neural, 6 aspectos sin?pticos e sinaliza??o Notch. Ambos os indiv?duos foram diagnosticados com DCF do tipo Taylor, mais especificadamente, do tipo IIb. No geral, os indiv?duos displ?sicos apresentaram altera??es na quantifica??o relativa na maioria dos genes analisados comparados aos indiv?duos controle, em todos os processos e grupos de estudo (fibroblastos, tecido cerebral, iPSCs e c?lulas neurodiferenciadas). Os genes envolvidos nos processos de migra??o e diferencia??o neural, aspectos sin?pticos e sinaliza??o Notch apresentaram express?es bastante alteradas nos indiv?duos displ?sicos, com o in?cio da maioria dos processos precoces, antes do per?odo fisiologicamente t?pico. A partir dos resultados encontrados, podemos inferir que durante o per?odo embrion?rio, no processo de neurog?nese e neurodiferencia??o, indiv?duos acometidos pela doen?a, possivelmente possuem neuroblastos mais sens?veis a est?mulos, apresentando diferen?as no desenvolvimento do Sistema Nervoso. Essas altera??es podem estar diretamente relacionadas com a forma??o do c?rebro displ?sico. Este trabalho amplia a compreens?o do neurodesenvolvimento embrion?rio, abrindo portas para futuras investiga??es de forma mais aprofundada sobre o envolvimento e influ?ncia de cada um dos genes analisados na patog?nese da DCF, bem como em cada mecanismo de a??o envolvido na forma??o do c?rebro.

Made available in DSpace on 2016-07-27T14:20:14Z (GMT). No. of bitstreams: 1 CRISTINA MARIA BRILHANTE DA SILVA.PDF: 1529940 bytes, checksum: 7aba7f50418f9237ead026c762846fbe (MD5) Previous issue date: 2013-10-07 / Resilience can beunderstood as a dynamic process involving a positive adjustment despite of the circumstances of significant adversity. Though, when it comes to families that have children with cerebral palsy, the resilience process is a reality for the mothers interviewed in this research. However, the family s resilience phenomenon is a context that requires investigation from a conceptual and methodological point of view. This paper presents and discusses the coping, possibilities and adversities within the family circle. A notion of applied resilience in Psychology was taken as a basis. Thus, the goal of this study is to spot the resilience strategies of six mothers of kids with cerebral palsy among the numberless risk factors. For this, a qualitative research was employed, so that an action-research was used as an intervention, and the data collection was done by a focus group technique, being performed at APAE in Anápolis-GO. The development was guided by theoretical of the family resilience phenomena grounded in family beliefs of Walsh (2005). During the investigation a systematic chart of resilience process in mothers was obtained, which provides arrow indicators for coping strategies to other mothers in similar situations. From these charts, illustrative charts were elaborate which allowed presenting a general perspective of the attendant s speeches brought up in the focus group. They also made it possible to visualize the mother s common trajectory efficiently and positively. In general, the obtained data emphasizes the coping strategies, the beliefs expressed, in which the most presented were: sense of coherence and meaning, self faith and faith in God; active initiative and shared responsibility. Also, the undertaken actions that happened through the search of specialized treatment to people with cerebral palsy; the pursuit of rights and benefits were also found; furthermore, protection factors such as: APAE; PSF; friend and neighborhood were detected. Although, the results presented, there are others, such as: interaction nature that focused the backing: emotional, material, of information and evaluation. And finally, the other results presented were BPC admission, child s enrollment at APAE; neighbors start to help and specialized care acquisition. In conclusion, family resilience is real and has a lot to contribute and teach not only the families with disabled members, but also any family that faces this conflict regardless its nature. Therefore, the results awake the notion focus groups play a role as an indicator of protection in the family resilience demonstration.(Appendix I). / Resiliência pode ser compreendida como um processo dinâmico envolvendo uma adaptação positiva frente às circunstâncias de adversidade significativa. Entretanto, quando se trata de famílias que têm filhos com paralisia cerebral, o seu processo de resiliência é uma realidade presente nas mães entrevistadas nessa pesquisa. No entanto, o fenômeno da resiliência familiar é um contexto que requer investigações do ponto de vista conceitual e metodológico. Este trabalho apresenta e discute os enfrentamentos, possibilidades e adversidades presentes no círculo familiar. Tomou-se como base a noção de resiliência aplicada na Psicologia. Portanto, o objetivo deste estudo foi identificar as estratégias de resiliência em seis mães de filhos com paralisia cerebral em meio há inúmeros fatores de risco. Para isso, empregou-se pesquisa qualitativa, de modo que se utilizou a pesquisa-ação como intervenção, e a coleta de dados teve como instrumento a técnica de grupo focal, sendo realizado na APAE de Anápolis- GO. O desenvolvimento foi pautado nos pressupostos teóricos do fenômeno da resiliência familiar fundamentado nos estudos das crenças familiares de Walsh (2005). No percurso da investigação obteve-se uma tabela sistemática do processo de resiliência em mães, que fornecem setas indicadoras para estratégia de superação para outras mães em condições similares. Dessas tabelas, se elaborou gráficos ilustrativos que permitiram apresentar um panorama geral dos discursos das participantes levantados no grupo focal. Também possibilitaram visualizar a trajetória comum das mães de modo eficaz e positivo. Em termos gerais, os dados obtidos enfatizaram as estratégias de enfrentamento, as crenças expressadas, das quais as mais apresentadas foram: senso de coerência e significado; fé em si e em Deus; iniciativa ativa e responsabilidade compartilhada. Como também, as ações empreendidas que se deram por meio da busca de tratamentos especializados para pessoa com paralisia cerebral; ainda verificou-se a procura de direitos e benefícios; o ingresso do filho na instituição da APAE e o solicitar ajuda à vizinhança. Além disso, foram detectados os fatores de proteção apontados como: APAE; PSF; amigos e vizinhança. Embora os resultados apresentados, ainda temos outros, tais como: natureza de interação que enfocou os suportes: emocional, material, de informação e de avaliação. E por fim, os demais resultados apresentados foram: admissão do BPC, ingresso do filho na APAE, a vizinhança passa ajudar e aquisição de atendimentos especializados. Conclui-se que a resiliência familiar é real e tem muito a contribuir e ensinar não apenas às famílias com pessoa com deficiência, mas qualquer família que passa por conflito seja qual for sua natureza. Portanto, os resultados despertaram a noção de que os grupos focais cumprem um papel de indicador de proteção na manifestação de resiliência familiar (APÊNDICE I).

Para o lançamento de novos produtos na área do Design de Moda, os designers utilizam conceitos de ergonomia durante as etapas de formatação do produto. A pesquisa tem como objetivo introduzir na metodologia projetual a preocupação ergonômica, visando à adequação do design no que diz respeito à usabilidade e ao conforto. O estudo trata das relações entre Moda, Design e Metodologia para compreensão da importância da Ergonomia no auxílio dos projetos de Design de Moda. A proposta é sistematizar por meio da metodologia de Grupo Focal as questões ergonômicas na fase projetual de produtos por meio de uma revisão bibliográfica e de reflexões extraídas, constatando-se sua aplicabilidade ao permitir que o designer a partir de uma análise qualitativa dos dados captados nas discussões com o público-alvo proporcione um produto mais satisfatório ao usuário. / For the launch of new products in the area of Fashion Design, designers use concepts of ergonomics through the steps of formatting the product. The research aims at introducing a methodology projetual ergonomic concern, aiming at adapting the design with regard to usability and comfort. The study deals with the relationship between Fashion, Design and Methodology for understanding the importance of ergonomics in aid of Fashion Design projects. The proposal is to systematize through focus group methodology ergonomic issues in projetual phase products through a literature review and reflections drawn, though there is its applicability by allowing the designer from a qualitative analysis of the data captured in discussions with the audience provides the user a more satisfactory product.

Superconductor-Insulator-Superconductor (SIS) mixers offer the best noise properties of any heterodyne mixing technique at millimetre wavelengths. In astronomy, they are used for sensitive spectroscopy, which is vital for understanding the properties of the cold interstellar medium, including regions of star formation activity. Modern SIS receivers have noise properties that are ∼3 times the quantum limit, and it is now becoming increasingly difficult to lower the noise properties any further. In this thesis, I investigate two techniques that extend the capability of SIS receivers. The first technique is extending the instantaneous bandwidth of the receivers, i.e., the intermediate frequency bandwidth (IFBW). For spectral line sources, wide IFBW expands the survey depth to allow multiple emission lines to be observed simultaneously. Here, I present a new SIS mixer device at 230 GHz. The planar circuit was minimised to reduce any parasitic capacitances that may limit the IFBW. Experimentally, the device provides excellent noise temperatures down to 36 K and an IFBW extending from approximately 0-11 GHz. Simulation software was developed to better understand the performance of this device, and it suggests that the IFBW can be extended to higher frequencies if the IF measurement chain is upgraded. The second technique that I investigate is increasing the number of receivers in the focal plane of the receiver, i.e., adding more pixels. There are many challenges involved in this task including how to fit multiple receivers into a small space, how to properly cool the receiver, and how to deliver the local-oscillator signal. Here, I present a new 1 × 4 focal plane array. This array is acting as a demonstrator for a new array architecture that can be expanded into many more pixels in the future. It uses cascaded waveguide power splitters to divide the local-oscillator signal, and then waveguide directional couplers to combine the LO with the astronomical signals. Finally, I present CO(J=1→0) measurements from 34 galaxies in the 5MUSES survey. These measurements trace the amount of cold molecular gas present in these galaxies. By comparing these measurements to other metrics that trace star formation activity (e.g., infrared luminosity), I was able to form empirical relationships between the observed quantities. I also combined these results with other star formation studies from nearby and high redshift galaxies to form scaling relationships spanning a large fraction of cosmic time.

"Topographical and mechanical properties of adhesive substrates provide important biological cues that affect cell spreading, migration, growth, and differentiation. The phenomenon has led to the increased use of topographically patterned and flexible substrates in studying cultured cells. However, these studies may be complicated by various limitations. For example, the effects of ligand distribution and porosity are affected by topographical features of 3D biological constructs. Similarly, many studies of mechanical cues are compounded with cellular deformation from external forces, or limited by comparative studies of separate cells on different substrates. Furthermore, understanding cell responses to mechanical input is dependent upon reliable measurements of mechanical properties. This work addresses each of these issues. To determine how substrate topography and focal adhesion kinase (FAK) affect cell shape and movement, I studied FAK-null (FAK -/-) and wild type mouse 3T3 fibroblasts on chemically identical polystyrene substrates with either flat surfaces or micron-sized pillars, I found that, compared to cells on flat surfaces, those on pillar substrates showed a more branched shape, an increased linear speed, and a decreased directional stability, which were dependent on both myosin-II and FAK. To study the dynamic responses to changes in substrate stiffness without other confounding effects, I developed a UV-modulatable substrate that softens upon UV irradiation. As atomic force microscopy (AFM) proved inadequate to detect microscale changes in stiffness, I first developed and validated a microsphere indentation method that is compatible with fluorescence microscopy. The results obtained with this method were comparable to those obtained with AFM. The UV-modulatable substrates softened by ~20-30% with an intensity of irradiation that has no detectable effect on 3T3 cells on control surfaces. Cells responded to global softening of the substrate with an initial retraction followed by a gradual reduction in spread area. Precise spatial control of softening is also possible - while there was little response to posterior softening, anterior softening elicited a pronounced retraction and either a reversal of cell polarity or a significant decrease in spread area if the cells move into the softened region. In conclusion, these techniques provide advances in gaining mechanistic insight into cellular responses to topographical and mechanical cues. Additionally, there are various other potential applications of the novel UV-softening substrate, particularly in regenerative medicine and tissue engineering. "

The performance of a dedicated A/D converter located beneath each pixel is explored in this thesis. Specifically, a voltage to frequency converter coupled with a direct injection amplifier designed for use with an IR focal plane array is analyzed. This versatile implementation of a Readout Integrated Circuit can be found applicable to a wide variety of imaging technologies. Noise performance of the conversion system is theoretically calculated, and is supported by SPICE simulations using valid CMOS SPICE models. It is shown that a 10 transistor sub-pixel voltage to frequency analog to digital converter will produce noise that is less than the input shot noise. Design considerations will be addressed to ensure continued performance as the scale of the imagers increase to large format arrays.