O presente projeto de pesquisa trata da investigação detalhada dos aspectos relacionados à \'\'Região Ótima\" do campo de radiação, particularmente voltada a sistemas mamográficos. Tal região foi definida em pesquisas anteriores como a faixa do campo onde o sistema apresenta sua melhor performance em termos de resolução espacial, produzindo, portanto, imagens mais nítidas. A investigação aqui proposta tomará por base a associação de dois métodos de avaliação de sistemas de imagem radiológica, que empregam simulação computacional para determinar as Funções de Transferência de Modulação (FTMs) - método de simulação a partir da FEL [SCHIABEL92] e método de simulação a partir da FEP [MARQUES92] - devidas ao ponto focal em diversas orientações e posições do campo. A finalidade é propor um método de prever a existência e extensão da Região Ótima, bem como seu significado prático para a nitidez da imagem e para a utilização de equipamentos mamográficos não isotrópicos, através de comparações entre os modelos de simulação. A comprovação prática dos resultados e das conclusões foi complementada com avaliações de imagens radiográficas feitas com \"phantoms\". / The propose of this work is to make a detailed investigation related with the optimum region aspects of x-rays radiation fields, specially in mammographic systems. Previous researches defined the optimum region as a field range where the system produces the best performance and best sharpened images.This investigation is based on the association of two analysis methods of radiological imaging systems which use computational simulation to determine the focal spot Modulation Transfer Function (MTF) - simulation method of Spread Line Function [SCHIABEL92] and simulation method of Spread Point Function [MARQUES94] - in severa! orientations and x-ray field positions. The intent is to propose a method to preview the existence of the optimum region, as well its practical meaning for the image sharpness and the utilization of a non-isotropic mammographic equipment, through comparison between both simulation models. The practical validation of the results and conclusions was complemented with the valuation of some radiographic images made with \"phantoms\".

abstract: The development of new Ultra-Violet/Visible/IR range (UV/Vis/IR) astronomical instrumentation that use novel approaches for imaging and increase the accessibility of observing time for more research groups is essential for rapid innovation within the community. Unique focal planes that are rapid-prototyped, low cost, and provide high resolution are key. In this dissertation the emergent designs of three unique focal planes are discussed. These focal planes were each designed for a different astronomical platform: suborbital balloon, suborbital rocket, and ground-based observatory. The balloon-based payload is a hexapod-actuated focal plane that uses tip-tilt motion to increase angular resolution through the removal of jitter – known as the HExapod Resolution-Enhancement SYstem (HERESY), the suborbital rocket imaging payload is a Jet Propulsion Laboratory (JPL) delta-doped charge-coupled device (CCD) packaged to survive the rigors of launch and image far-ultra-violet (FUV) spectra, and the ground-based observatory payload is a star centroid tracking modification to the balloon version of HERESY for the tip-tilt correction of atmospheric turbulence. The design, construction, verification, and validation of each focal plane payload is discussed in detail. For HERESY’s balloon implementation, pointing error data from the Stratospheric Terahertz Observatory (STO) Antarctic balloon mission was used to form an experimental lab test setup to demonstrate the hexapod can eliminate jitter in flight-like conditions. For the suborbital rocket focal plane, a harsh set of unit-level tests to ensure the payload could survive launch and space conditions, as well as the characterization and optimization of the JPL detector, are detailed. Finally, a modification of co-mounting a fast-read detector to the HERESY focal plane, for use on ground-based observatories, intended to reduce atmospherically induced tip-tilt error through the centroid tracking of bright natural guidestars, is described. / Dissertation/Thesis / Doctoral Dissertation Exploration Systems Design 2019

Recombinant adeno-associated virus (rAAV) is a widely used gene therapy vector. Although a wide range of rAAV serotypes can effectively enter most cell types, their transduction efficiencies (i.e., transgene expression) can vary widely depending on the target cell type. Integrins play important roles as co-receptors for rAAV infection, however, it remains unclear how integrin-dependent and -independent mechanisms of rAAV endocytosis influence the efficiency of intracellular virus processing and ultimately transgene expression. In this thesis, I examined the contribution of integrin-mediated endocytosis to transduction of fibroblasts by rAAV2. I found that promoting AAV2/integrin binding with Mn++ greatly enhanced (~17-fold) rAAV2 transduction independently of cell binding and endocytosis. Subcellular localization studies of rAAV2 demonstrated that integrin activation by Mn++ promoted AAV2 aggregation on alpha5 and beta1 integrins and recruitment of the cytosolic integrin effector protein vinculin. Focal adhesion kinase (FAK), a down stream effector of integrin signals, was essential for AAV/integrin complex endocytosis and transduction, but not AAV2 recruitment to integrins. Recruitment of FAK to AAV2/integrin complexes was increased by transiently trapping the endocytic event at the plasma membrane by pharmacologic inhibition of dynasore. This also increased the size of AAV2 clusters found beneath the cell at FAK/integrin complexes resembling immature filopodia and caused a large, FAK-dependent (75-fold) increase in AAV2 transduction. These findings support a model whereby integrin activation at the cell surface can redirect rAAV2 toward a FAK-dependent entry pathway that is more productive for cellular transduction. This pathway appears to be conserved for other rAAV serotypes that contain a capsid integrin-binding domain (AAV1 and 6).

The degree of academic achievement following early onset brain injury is poorly understood. Furthermore, it is unclear if academic success can be predicted by age of onset or other lesion variables (e.g., size, laterality). The purpose of the current study was to describe patterns of academic achievement in individuals with childhood-onset focal brain lesions and to determine the role of variables in the plasticity or vulnerability of the developing brain with regard to achievement. Academic achievement data were collected from 58 individuals with childhood-onset focal brain lesions. The participants' reading, spelling, and arithmetic scores, as measured by the Wide Range Achievement Test, were analyzed in relation to several neuroanatomical variables, including lesion laterality, lesion site, and lesion size. The relationship between achievement and gender, age of onset, etiology, age at testing, and time since lesion onset was also identified. As a group, achievement scores did not differ from normative data, and the majority of the sample demonstrated adequate skills in each domain. However, the frequency of deficits was larger than expected when compared to base rates, suggesting vulnerability to early insult. Achievement scores were correlated with intelligence scores, but did not differ based on lesion laterality, lesion site, age of onset, or etiology. Size of lesion was significantly correlated with reading and spelling but not with arithmetic outcomes. Gender differences were identified, with males performing significantly better on the arithmetic measure than females. The age of onset, age at testing, and time since lesion onset were not correlated with achievement scores in any domain. No interactions were found between lesion laterality and gender or lesion site and lesion laterality. An interaction between gender and lesion site was found, but the significance of the finding is unclear. The current findings provide mixed evidence for the plasticity-vulnerability debate, as many individuals were able to achieve adequate academic skills whereas others demonstrated significant impairments. Further research is needed to elucidate factors that may predict achievement outcomes in individuals with childhood-onset focal brain injury.

Popular and consumer cultures share a similar trajectory in the United States with spectacle and money being key ingredients in the construction of both. This is most apparent in the sports industry in America with billions of dollars in revenue generated every year. During the first half of the twentieth century sports like baseball and boxing commanded a significant amount of cultural and economic capital. It was not unheard of for sports teams, talented athletes and even a few select coaches to ascend to a legendary or even mythical status. The spectacle and revenue generating capacity of amateur and professional sports was considerable during this time, but it was not until the early 1960s that the true potential for an American sports was constructed. The introduction of television in the development of the National Football Leagues spectacle redefined what sports in the United States means to popular and consumer cultures. The enormity of the National Football Leagues premier annual spectacle, the Super Bowl, is a testament to the sports dominance of American popular and consumer cultures. By analyzing the National Football Leagues formative years during the 1960s and 1970s, it is my intention to demonstrate how the NFL was able to reframe its cultural product, and achieve an unprecedented social and economic status in American culture. I will employ an organization set analysis of cultural industry systems proposed by Paul M. Hirsch in conjunction with Clifford Geertz and Jerome Bruners studies on the cultural power and significance of the narrative form to trace the trajectory of the NFLs social and economic success. Popular fiction will also be included to demonstrate how thoroughly professional football infiltrated popular and consumer cultures and changed how Americans viewed televised sports. American sports have undergone amazing changes over the last century, but it was the National Football League and television that changed what the sports industry means to American culture.

<p>Integrins are heterodimeric cell surface receptors, composed of an α and a β subunit, mainly binding for extracellular matrix proteins. lntegrin subunit β1 can combine with at least 12 a subunits and thus form the biggest subfamily within the integrin family. In this thesis, functional properties of the splice variant β1Β, and the effects of several mutations in the cytoplasmic tail of integrin subunit β1Α were studied. In addition, the border between the transmembrane and cytoplasmic domains of several integrin subunits was determined.</p><p>The β1Β splice variant has been reported to have a dominant negative effect on functions of β1Α integrins. In this study, it was studied if the expression of β1Β had similar negative effects on the αvβ3 integrin functions since the β3 subunit is structurally similar to β1Α. The β1Β subunit was expressed in an integrin β1-deficient cell line and it was found that the presence of β1Β does not interfere with adhesion or signaling of endogenous αvβ3</p><p>The border between the cytoplasmic domain and the C-terminal end of the transmembrane domain of integrin α and β subunits has been unclear. This question was experimentally addressed for integrin subunits β1, β2, α2 and α5. It was found that integrin subunits contain a positively charged lysine, which is embedded in the membrane in the absence of interacting proteins.</p><p>The functional importance of the lysine in integrin transmembrane domains was investigated by mutating this amino acid to leucine in β1Α. The mutation affected cell spreading and tyrosine phosphorylation of the adapter protein CAS. The activation of focal adhesion kinase and tyrosine phosphorylation of paxillin was not affected. Furthermore, the mutation of two tyrosines to phenylalanines in the β1Α cytoplasmic tail was found to reduce the capability of β1Α integrins to mediate cell spreading and migration. Activation of focal adhesion kinase in response to the later β1Α mutant was shown to be impaired as well as tyrosine phosphorylation of adapter proteins paxillin and tensin whereas overall tyrosine phosphorylation of CAS was unaffected. These data suggests the presence of focal adhesion kinase-dependent and -independent pathways for tyrosine phosphorylation of CAS after integrin β1Α-mediated adhesion. </p>

The cytoskeleton is a diverse, multi-protein framework that plays a fundamental role in many cellular activities including mitosis, cell division, intracellular transport, cell motility, muscle contraction, and the regulation of cell polarity and organization. Furthermore, cytoskeletal filaments have been implicated in the pathogenesis of a wide variety of diseases including cancer, blood disease, cardiovascular disease, inflammatory disease, neurodegenerative disease, and problems with skin, nail, cornea, hair, liver and colon. Increasing evidence suggests that the distribution and organization of the cytoskeleton in living cells are affected by mechanical stresses and the cytoskeleton determines cell stiffness. We developed a fully nonlinear, constrained mixture model for adherent cells that allows one to account separately for the contributions of the primary structural constituents of the cytoskeleton and extended a prior solution from the finite elasticity literature for use in a sub-class of atomic force microscopy (AFM) studies of cell mechanics. The model showed that the degree of substrate stretch and the geometry of the AFM tip dramatically affect the measured cell stiffness. Consistent with previous studies, the model showed that disruption of the actin filaments can reduce the stiffness substantially, whereas there can be little contribution to the overall cell stiffness by the microtubules or intermediate filaments. To investigate the effect of mechanical stretching on cytoskeletal remodeling and cell stiffness, we developed a simple cell-stretching device that can be combined with an AFM and confocal microscopy. Results demonstrate that cyclic stretching significantly and rapidly alters both cell stiffness and focal adhesion associated vinculin and paxillin, suggesting that focal adhesion remodeling plays a critical role in cell stiffness by recruiting and anchoring F-actin. Finally, we estimated cytoskeletal remodeling by synthesizing data on stretch-induced dynamic changes in cell stiffness and focal adhesion area using constrained mixture approach. Results suggest that the acute increase in stiffness in response to an increased cyclic stretch was probably due to an increased stretch of the original filaments whereas the subsequent decrease back towards normalcy was consistent with a replacement of the highly stretched original filaments with less stretched new filaments.

<p>I tolkningen av vad en doktrin är, så finns både ett inriktande syfte och en slags ensning av det förhållningssätt som gäller och förväntas av Försvarsmaktens personal. Det innebär att man skulle kunna förvänta sig en tydlig viktning mot det internationella fokus som faktiskt klart kan sägas gälla efter försvarsbeslutet 2004. Frågan blir då om de tre svenska arenadoktrinerna är tillräckligt tydliga i att poängtera detta. Denna uppsats försöker därför analysera doktrinerna och utröna om det egentligen finns något fokus avseende nationella och internationella insatser och om det i så fall finns någon skönjbar förklaring till detta i doktrintexterna. Undersökningen består av en kvantitativ textanalys samt en kvalitativ undersökning av doktrinerna för luft-, mark- och marina operationer, som tillsammans angriper texterna baserat på två definierade indikatorer av fokuseringarna.</p><p>Analysen i uppsatsen ger vid handen att doktrinen för marina operationer visar en märkbart större fokusering vid internationella insatser än vad de andra gör. Detta kan bero på skillnader i påverkan av stridens genomförande av att insatsen sker nationellt eller internationellt.</p> / <p>In the interpretation of the meaning of a doctrine, there is both a purpose of direction as well as unifying the posture that all personnel in the Swedish Armed Forces are expected to have. That means that a corresponding prioritization could be equally expected of international missions, which are safe to say is the focal point for the Swedish Armed Forces after the defense policy decision made in 2004. The question therefore arises whether or not the three Swedish arena doctrines are adequate in showing these postures. This essay comprises both a quantitative and a qualitative text analysis of the arena doctrines, which together penetrates the texts based on two defined indicators of these focal points.</p><p>The results of this essay are that the doctrine for maritime operations shows a noticeable larger focusing on international missions than the other two does. This might come from the difference in how the arena is affected in the basic tasking depending on whether the mission is conducted nationally or internationally.</p>

Integrins are heterodimeric cell surface receptors, composed of an α and a β subunit, mainly binding for extracellular matrix proteins. lntegrin subunit β1 can combine with at least 12 a subunits and thus form the biggest subfamily within the integrin family. In this thesis, functional properties of the splice variant β1Β, and the effects of several mutations in the cytoplasmic tail of integrin subunit β1Α were studied. In addition, the border between the transmembrane and cytoplasmic domains of several integrin subunits was determined. The β1Β splice variant has been reported to have a dominant negative effect on functions of β1Α integrins. In this study, it was studied if the expression of β1Β had similar negative effects on the αvβ3 integrin functions since the β3 subunit is structurally similar to β1Α. The β1Β subunit was expressed in an integrin β1-deficient cell line and it was found that the presence of β1Β does not interfere with adhesion or signaling of endogenous αvβ3 The border between the cytoplasmic domain and the C-terminal end of the transmembrane domain of integrin α and β subunits has been unclear. This question was experimentally addressed for integrin subunits β1, β2, α2 and α5. It was found that integrin subunits contain a positively charged lysine, which is embedded in the membrane in the absence of interacting proteins. The functional importance of the lysine in integrin transmembrane domains was investigated by mutating this amino acid to leucine in β1Α. The mutation affected cell spreading and tyrosine phosphorylation of the adapter protein CAS. The activation of focal adhesion kinase and tyrosine phosphorylation of paxillin was not affected. Furthermore, the mutation of two tyrosines to phenylalanines in the β1Α cytoplasmic tail was found to reduce the capability of β1Α integrins to mediate cell spreading and migration. Activation of focal adhesion kinase in response to the later β1Α mutant was shown to be impaired as well as tyrosine phosphorylation of adapter proteins paxillin and tensin whereas overall tyrosine phosphorylation of CAS was unaffected. These data suggests the presence of focal adhesion kinase-dependent and -independent pathways for tyrosine phosphorylation of CAS after integrin β1Α-mediated adhesion.

I tolkningen av vad en doktrin är, så finns både ett inriktande syfte och en slags ensning av det förhållningssätt som gäller och förväntas av Försvarsmaktens personal. Det innebär att man skulle kunna förvänta sig en tydlig viktning mot det internationella fokus som faktiskt klart kan sägas gälla efter försvarsbeslutet 2004. Frågan blir då om de tre svenska arenadoktrinerna är tillräckligt tydliga i att poängtera detta. Denna uppsats försöker därför analysera doktrinerna och utröna om det egentligen finns något fokus avseende nationella och internationella insatser och om det i så fall finns någon skönjbar förklaring till detta i doktrintexterna. Undersökningen består av en kvantitativ textanalys samt en kvalitativ undersökning av doktrinerna för luft-, mark- och marina operationer, som tillsammans angriper texterna baserat på två definierade indikatorer av fokuseringarna. Analysen i uppsatsen ger vid handen att doktrinen för marina operationer visar en märkbart större fokusering vid internationella insatser än vad de andra gör. Detta kan bero på skillnader i påverkan av stridens genomförande av att insatsen sker nationellt eller internationellt. / In the interpretation of the meaning of a doctrine, there is both a purpose of direction as well as unifying the posture that all personnel in the Swedish Armed Forces are expected to have. That means that a corresponding prioritization could be equally expected of international missions, which are safe to say is the focal point for the Swedish Armed Forces after the defense policy decision made in 2004. The question therefore arises whether or not the three Swedish arena doctrines are adequate in showing these postures. This essay comprises both a quantitative and a qualitative text analysis of the arena doctrines, which together penetrates the texts based on two defined indicators of these focal points. The results of this essay are that the doctrine for maritime operations shows a noticeable larger focusing on international missions than the other two does. This might come from the difference in how the arena is affected in the basic tasking depending on whether the mission is conducted nationally or internationally.