Thesis (MSD(Social Work and Criminology))-University of Pretoria, 2007. / Includes bibliographical references.

Hohe Benutzertauglichkeit und Akzeptanz eines Webseitenservices sind nur dann gewährleistet, wenn diese auf die funktionalen Bedürfnisse, aber auch auf die strukturellen Vorstellungen ihrer Benutzer zugeschnitten sind. Im Kontext einer Webseite zur „Suche nach E-Learning-Produkten im Internet“ wurde untersucht, inwieweit die Kenntnis der Mentalen Modelle potenzieller Nutzer den Softwareentwicklungsprozess positiv beeinflussen kann. Dabei erlaubte die Erhebung Mentaler Modelle mit Hilfe der Struktur-Lege-Technik (SLT) als Evaluationsmethode einen Vergleich mit der tatsächlich entwickelten Webseite. Die Studie zeigte, dass trotz zuvor bereits durchgeführter, klassischer Evaluationen (Usability Tests, Anwendung von Heuristiken und Cognitive Walkthroughs) 40 Funktionsbereiche genannt wurden, die auf der tatsächlichen Webseite nicht vorgesehen oder umgesetzt sind. Daraus folgt, dass die Erhebung von Mentalen Modellen ebenfalls bereits vor dem Software-Entwicklungsprozess durchgeführt werden soll.

Indiana University-Purdue University Indianapolis (IUPUI) / Down syndrome (DS) is the result of trisomy of human chromosome 21 (Hsa 21) and occurs in approximately 1/700 live births. Mouse models of DS have been crucial in understanding the gene-phenotype relationships that underlie many DS anomalies. The Ts65Dn mouse model, trisomic for half of the Hsa 21 orthologs replicates many DS phenotypes including craniofacial alterations such as a small, dysmorphic mandible, midface, and maxilla. Other mouse models, such as the Ts1Rhr which contains a triplication of 33 Hsa 21 orthologs, have been used to better understand the genes responsible for craniofacial alterations. Our laboratory has demonstrated that the postnatal mandibular phenotype found in Ts65Dn mice can be traced back to an original neural crest cell (NCc) deficit in the developing first pharyngeal arch (PA1) at embryonic day 9.5 (E9.5). Furthermore, evidence suggested that both a proliferation deficit in the PA1 and a migration deficit in the NCC from the neural tube (NT) could be the mechanism behind this deficit. However, the molecular mechanisms behind these deficits remain to be elucidated. Due to the involvement of the Hsa 21 genes DYRK1A and RCAN1 in regulation of signaling pathways including NFATc (NFAT2), a transcription factor known to influence cellular proliferation and, later, bone development, we hypothesized that dysregulation of these genes could underlie the cellular deficit in the PA1. Furthermore, we hypothesized that targeting Dyrk1a by decreasing activity or available protein could ameliorate the established deficits. Through the use of RNA isolation techniques and cell culture systems of cell from the PA1 and NT of E9.5 Ts65Dn, Ts1Rhr, and control embryos, we established that trisomic genes Dyrk1a and Rcan1 ara dysregulated in both structures and that these two genes may interact. Furthermore, we established that a proliferation deficit in the Ts65Dn PA1 and a migration deficit in the Ts65Dn PA1 and NT exists at E9.5 and can be rescued to euploid levels in vitro with the addition of the Dyrk1a inhibitor, EGCG, a green tea polyphenol. We also confirmed that harmine, a more highly studied and specific Dyrk1a inhibitor, is capable of similar effects on proliferation of PA1 cell from E9.5 Ts65Dn embryos. Furthermore, when Ts65Dn pregnant mothers were treated with EGCG in vivo, the cellular deficit found in the developing E9.5 embryonic PA1 was rescued to near euploid volume and NCC number. Treatment with EGCG did not adversely impact litter size or embryonic development. Interestingly, euploid embryonic volume increased with EGCG treatment. Expression analysis of the E9.5 PA1 of EGCG treated Ts65Dn and control embryos revealed dysregulation of several genes involved in craniofacial and developmental pathways including Dyrk1a, Rcan1, Ets2 and members of the sonic hedgehog pathways. Our novel results provide a foundation for better understanding the molecular mechanisms of craniofacial development and may provide evidence-based therapeutic options to improve the quality of life for individuals with DS.

[pt] A partir de um estudo comparado de Brasil e Chile, expoentes da chamada divisão Atlântico vs. Pacífico, buscamos entender os fatores que influenciaram na elaboração e promoção de diferentes projetos regionais entre 2006 e 2014. Lançando mão de instrumentos metodológicos como a Análise de Conteúdo (AC) e a Análise Documental (AD), realizamos uma análise pormenorizada da relevância das seguintes variáveis: (a) ideologia política; (b) modelos de democracia; (c) modelos de desenvolvimento e (d) eixos geoestratégicos. Concluímos que o impacto da ideologia política sobre a elaboração e promoção de estratégias de regionalismo foi menos relevante que as demais condicionantes. Em um cenário de oportunidades e restrições impostas pelas relações estratégicas com os EUA e China, os modelos de democracia e, especialmente, os modelos de desenvolvimento foram as condicionantes mais expressivas nas políticas externas para o regionalismo empreendidas por Brasil e Chile entre 2006 e 2014. Portanto, o regionalismo latino-americano é melhor definido como determinado por eixos de regionalismo com singularidades que vão além de uma lógica fundamentada na dicotomia esquerda e direita. / [en] Based on a comparative study of Brazil and Chile, exponents of the so-called Atlantic vs. Pacific, we seek to understand the factors that influenced the elaboration and promotion of different regional projects between 2006 and 2014. Using methodological instruments such as Content Analysis (CA) and Document Analysis (AD), we carried out a detailed analysis of the relevance of following variables: (a) political ideology; (b) models of democracy; (c) models of development and (d) geostrategic axes. We conclude that the impact of political ideology on the elaboration and promotion of regionalism strategies was less relevant than the other constraints. In a scenario of opportunities and restrictions imposed by strategic relations with the USA and China, the models of democracy and, especially, the models of development were the most expressive conditions in the external policies for regionalism undertaken by Brazil and Chile between 2006 and 2014. Therefore, Latin American regionalism is best defined as determined by axes of regionalism with singularities that go beyond a logic based on the left and right dichotomy. / [es] A partir de un estudio comparativo de Brasil y Chile, exponentes del llamado Atlántico vs. Pacífico, buscamos comprender los factores que influyeron en la elaboración y promoción de diferentes proyectos regionales entre 2006 y 2014. Utilizando instrumentos metodológicos como el Análisis de Contenido (CA) y el Análisis Documental (AD), realizamos un análisis detallado de la relevancia de las siguientes variables: (a) ideología política; (b) modelos de democracia; (c) modelos de desarrollo y (d) ejes geoestratégicos. Concluimos que el impacto de la ideología política en la elaboración y promoción de estrategias de regionalismo fue menos relevante que las otras limitaciones. En un escenario de oportunidades y restricciones impuestas por las relaciones estratégicas con Estados Unidos y China, los modelos de democracia y, especialmente, los modelos de desarrollo fueron las condiciones más expresivas en las políticas externas para el regionalismo emprendidas por Brasil y Chile entre 2006 y 2014. Por tanto, el regionalismo latinoamericano se define mejor como determinado por ejes de regionalismo con singularidades que van más allá de una lógica basada en la dicotomía izquierda y derecha.