Ο ιός της ηπατίτιδας C (HCV) είναι η κύρια αιτία της χρόνιας ηπατίτιδας. Το γενετικό υλικό του ιού είναι ένα μονόκλωνο RNA θετικής πολικότητας μήκους 9600 νουκλεοτιδίων, που κωδικοποιεί ένα ανοιχτό πλαίσιο ανάγνωσης. Στα 5’ και 3’ άκρα της κωδικής περιοχής υπάρχουν ιδιαίτερα συντηρημένες και με έντονη δευτεροταγή δομή μη μεταφραζόμενες περιοχές. Αντίθετα με το γενικό κανόνα, η έναρξη της μετάφρασης του γονιδιώματος πραγματοποιείται με το μηχανισμό της εσωτερικής πρόσδεσης του ριβοσώματος (IRES). Η αλληλουχία RNA που απαιτείται για τη λειτουργία IRES, περιλαμβάνει όλη την 5’ μη- μεταφραζόμενη περιοχή, εκτός της περιοχής I, και τα πρώτα 75 νουκλεοτίδια της κωδική περιοχής. Μέχρι τώρα είναι γνωστό ότι μέσω της HCV IRES εξαρτώμενης μετάφρασης εκφράζονται όλες οι δομικές και μη δομικές πρωτεΐνες του ιού. Με την βοήθεια δισιστρoνικών συστημάτων μελέτης έχει δειχθεί ότι η HCV IRES εξαρτώμενη μετάφραση του γονιδιώματος του ιού καταστέλλεται από την μη-δομική πρωτεΐνη NS5Α του ιού. Σκοπός της παρούσας διπλωματικής εργασίας είναι α) να διερευνηθεί εάν η καταστολή αυτή της HCV IRES εξαρτώμενης μετάφρασης του ιού επηρεάζεται από την παρουσία των υπολοίπων μη δομικών πρωτεϊνών και β) να διερευνηθεί εάν το φαινόμενο αυτό παρατηρείται και στα υπόλοιπα μέλη της οικογένειας Flaviviridae και συγκεκριμένα στον GBV-B ιό. Τα αποτελέσματα έδειξαν ότι η HCV IRES εξαρτώμενη μετάφραση του ιού που καταστέλλεται από την HCV NS5A δε μεταβάλλεται παρουσία των υπολοίπων μη δομικών πρωτεϊνών. Σε αντίθεση η GBV-B NS5A δε φαίνεται να έχει την ικανότητα καταστολής της μετάφρασης μέσω του ομόλογου GBV-B IRES / -

This dissertation consists of three papers on diversity and diversity policy within organizations in general and within police forces in Europe in particular. The first paper provides an analytical framework that identifies fundamental choices in the definition of diversity (ontological dimension), in the motivation for diversity within organisations (deontological dimension), and in diversity policy as an organizational strategy (instrumental dimension). The second paper provides an overview of empirical data on diversity within police forces in Europe, identifies important research gaps in the field, and proposes a comprehensive view to structure future comparative research. The third paper compares two regional police forces (the Mossos d’Esquadra and the Politie Utrecht) and shows similarities in definitions and motivations for diversity, but differences in approach. It also demonstrates the academic potential of the empirical application of the analytical framework, and confirms that diversity and diversity policy are multilayered concepts in theory and in practice. / La siguiente tesis de doctorado está compuesta por tres artículos sobre diversidad y políticas de diversidad en organizaciones en general, y en fuerzas policiales en particular. El primer artículo ofrece un marco analítico que identifica elecciones fundamentales en la definición de diversidad (dimensión ontológica), en la motivación para diversidad dentro de las organizaciones (dimensión deontológica), y en las políticas de diversidad como estrategia organizacional (dimensión instrumental). El segundo artículo proporciona datos empíricos sobre la diversidad dentro de las fuerzas policiales en Europa, identifica agujeros importantes en este campo de estudio, y propone una perspectiva comprensiva para estructurar futuros estudios comparativos. El tercer y último artículo compara dos fuerzas policiales regionales (los Mossos d’Esquadra y la Politie Utrecht), mostrando similitudes entre ambos en sus definiciones y motivaciones versus diferencias en sus métodos. De la misma forma, queda demostrado el potencial académico del marco analítico en el mundo empírico, confirmando que diversidad y políticas de diversidad son conceptos con múltiples niveles en la teoría y en la práctica.

In this thesis, I analyze the contribution of the economic context to the fertility and mortality crises that took place across the former Soviet Union and Central and Eastern Europe during the transition from communism. At the macro-level, findings reflect a relationship between a negative economic context and stopping behavior of childbirth, whereas a positive economic context appears to encourage postponement of having a first child. Macro-economic conditions appear to be related to variations in mortality rates as well, particularly for the demographic group that drove the mortality crisis and the causes of death that have been linked to alcohol consumption. At the micro-level, evidence emerges in Russia that downward social mobility and unemployment were two experiences that particularly influenced early deaths and second birth risks. Both women and men were less likely to have a second child if they had experienced downward mobility after the first child was born. While excessive alcohol consumption and poor health did not predict downward social mobility or unemployment, the reverse relationship did appear in the findings. / En esta tesis, analizar la contribución del contexto económico de la fecundidad y la mortalidad de las crisis que tuvo lugar en la antigua Unión Soviética y Europa Central y Oriental durante la transición del comunismo. A nivel macro, los resultados reflejan una relación entre un contexto económico negativo y detener el comportamiento del parto, mientras que un contexto económico positivo parece fomentar el aplazamiento de tener un primer hijo. Condiciones macroeconómicas parecen estar relacionadas con variaciones en las tasas de mortalidad y, en particular para el grupo demográfico que llevó a la crisis de mortalidad y las causas de la muerte que se han vinculado al consumo de alcohol. A nivel micro, la evidencia que surge en Rusia la baja movilidad social y el desempleo son dos experiencias en particular que influyó en las muertes tempranas y el segundo nacimiento riesgos. Tanto hombres como mujeres tenían menos probabilidades de tener un segundo hijo si habían experimentado movilidad descendente después del primer hijo nació. Mientras que el consumo excesivo de alcohol y la mala salud no predicen la baja movilidad social o el desempleo, la relación inversa que aparecen en los resultados.

Esta tesis doctoral investiga cómo el cuidado parental varía por educación, género, clase social y países. Se usan datos de uso del tiempo para Gran Bretaña, Dinamarca, Flandes y España. Éstos son los resultados principales: (1) existen variaciones nacionales en el equilibrio “cuidado parental-empleo” entre los padres, pero no entre las madres, quienes muestran más diferencias por educación; (2) en España, el empleo femenino se correlaciona fuertemente con la participación paterna en actividades rutinarias/físicas en familias con niños preescolares; (3) existe un gradiente educativo paternal, relacionado con las etapas evolutivas y en consonancia con las prácticas de crianza recomendadas por “expertos” en paternidad; (4) en Gran Bretaña la clase social y la educación se correlacionan fuertemente con los estilos parentales asociados con la acumulación de capitales cultural, humano y social; (5) los hombres en ocupaciones post-industriales parecen identificarse particularmente con las normas de paternidad intensiva de “cultivo educacional”. / This doctoral dissertation investigates variations in parenting behavior by education, gender, social class, and countries. Time-diary data from Britain, Denmark, Flanders, and Spain are analyzed. The main findings are these: (1) cross-national variations in parenting-work balance are observed amongst fathers, but not amongst mothers, for which a more salient education gradient is observed; (2) in Spain, women’s employment is strongly correlated with paternal involvement in routine/physical activities in families with preschoolers; (3) a strong education gradient in fathering is correlated with children’s developmental stages, in line with those child-rearing practices recommended by “parenting experts”; (4) in Britain, social class and education are strongly correlated with those parenting styles associated with children’s accumulation of cultural, human, and social capital; (5) men in post-industrial occupations appear to be particularly identified with the fathering norms of intensive “educational cultivation”.

Glycogen Synthase Kinase-3 (GSK-3) is a highly conserved serine/threonine kinase comprised of two mammalian homologues, GSK-3α and β, encoded by independent genes. This thesis reports the characterization of GSK-3-null primary mouse embryonic fibroblasts (MEFs) generated by gene targeting to gain insight into the physiological functions of this protein kinase. Combined inactivation of both alleles of GSK-3α and GSK-β led to elevated sensitivity to TNFα-induced apoptosis, altered organization of focal adhesion complexes, defects in cell spreading on fibronectin, decreased cell growth associated with altered cell cycle progression through the G2/M phase and increased spontaneous apoptosis. Future work will focus on unraveling the molecular mechanisms responsible for these effects and identifying the common and distinct cellular roles for GSK-3α and β, and specific variants of these isoforms.

Homologous recombination (HR) is a precise mechanism for repairing harmful DNA double-strand breaks. The process has been extensively studied in microbial species leading to identification of the major proteins, HR models and homology requirements. Much less is known about HR in mammalian systems, especially early HR events. Our laboratory has recently devel-oped an assay that detects the new DNA synthesis that accompanies the early homology search and strand invasion steps of HR (the 3’ extension assay). The hypothesis that homology require-ments for the early steps of HR may differ from those identified in other HR assays was tested. Plasmids bearing varying amounts of homology to the chromosomal immunoglobulin μ target locus gene were constructed and tested in the 3’ extension assay. The homology require-ments for the 3’ extension assay were somewhat lower than might be expected based on other HR assays. An approximately linear relationship between homology length and 3’ extension was also established on each side of the double-strand break. The effect of excess Rad51, an essential protein involved in early HR, was also measured with respect to homology, leading to the dis-covery that increased Rad51 resulted in an increase in 3’ extension events independent of ho-mology. In summary, 3’ extension generates a potentially unstable, short-lived HR intermediate that has less dependence on homology than a completed HR product. Homology plays a role in the initiation of HR, but it may be more important in the stabilization of the intermediate than the actual generation of the early HR product detected in the 3’ extension assay. / CIHR

Proposem i provem empíricament un model integral de flux en un entorn virtual d’aprenentatge amb una orientació del consumidors. El nostre objectius és aclarir les ambigüitats i inconsistències existents a la literatura sobre la conceptualització i operacionalització de flux en contextos de navegació i de consum en general. El model, contrastat a través d’un qüestionari en línia amb una mostra de 2.574 estudiants, inclou un nou determinant de flux (personalització) i noves relacions entre les variables relacionada amb el flux. D’altra banda, es demostren dues conseqüències positives directes de flux (afecte positiu i aprenentatge). Aquest treball de recerca llança llum sobre els processos de navegació en línia i per tant, en un disseny més adequat per als entorns virtuals d’aprenentatge. / Proponemos y probamos empíricamente un modelo integral de flujo en un entorno virtual de aprendizaje con una orientación del consumidor. Nuestro objetivo es aclarar las ambigüedades e inconsistencias existentes en la literatura sobre la conceptualización y operacionalización de flujo en contextos de navegación y de consumo en general. El modelo, contrastado a través de un cuestionario en línea con una muestra de 2.574 estudiantes, incluye un nuevo determinante de flujo (personalización) y nuevas relaciones entre las variables relacionada con el flujo. Por otra parte, se demuestran dos consecuencias positivas directas de flujo (afecto positivo y aprendizaje). Este trabajo de investigación arroja luz sobre los procesos de navegación en línea y, por lo tanto, en un diseño más adecuado para los entornos virtuales de aprendizaje. / We propose and empirically test an integral flow model in a virtual learning environment with a consumer orientation. We aim at clarifying the ambiguities and inconsistencies existing in the literature regarding the conceptualization and operationalization of flow in general browsing and consumption contexts. The model, tested through an online questionnaire with a sample of 2,574 students, includes a new determinant of flow (personalization) and new relationships between the variables related to flow. Furthermore, two direct positive consequences of flow are proved (positive affect and learning). This research work sheds light on the processes of online browsing and, thus, on a more suitable design for virtual learning environments.

Bakgrund: Sedan den första januari år 2005 ska alla svenska börsnoterade koncerner till följd av EU-lagstiftning följa de internationella redovisningsreglerna IAS/IFRS. En av de redovisningsstandarder som finns i IFRS är IFRS 3 Business combinations som behandlar rörelseförvärv. Övergången till IFRS har lett till att det ställs högre krav på den information som företagen lämnar i samband med sina årsredovisningar jämfört med tidigare regler. Syfte: Att studera om det har skett en förbättring 2012 jämfört med 2006 av de upplysningar som ska lämnas enligt IFRS 3 av företagen noterade på Nasdaq OMX Stockholm. Vidare se om det finns något samband mellan upplysningsgrad och storlek på företagen. Metod: En kvantitativ metod har tillämpats där sekundärdata har samlats in från årsredovisningar för år 2006 och år 2012. Tre separata Chi2-test har sedan utförts för att se om det finns något samband. Empiri: Empirin visar att det har skett en viss förbättring mellan år 2006 och 2012, detta kan dock inte styrkas med Chi2-testet. År 2006 fanns det ett samband mellan börslista och uppfyllningsgrad men detta samband fanns inte år 2012. Slutsats: Det finns ett samband mellan börslista och uppfyllningsgrad år 2006 vilket kan styrkas med hjälp av ett Chi2-test. Detta samband kunde dock inte styrkas för år 2012 då uppfyllningsgraden har jämnats ut mellan åren. Utifrån diagrammen kan en viss förbättring ses när man jämför uppfyllelsegraden 2006 och 2012.

This work investigates methods to provide clinically useful visualisations of the data produced by an X-ray/CT scanner. Specifically, it examines the use of perceptual depth cues (PDCs) and perceptual depth cue theory to create effective visualisations. Two visualisation systems are explored: one to display X-ray data and the other to display volumetric data. The systems are enhanced using stereoscopic and motion PDCs. The presented analyses show that these are the only possible enhancements common to both systems. The theoretical and practical aspects of implementing these enhancements are presented. Volume rendering techniques are explored to find an approach which gracefully handles poorly sampled data and provides the interactive rendering needed for motion cues. A low cost real time volume rendering system is developed and a novel stereo volume rendering technique is presented. The developed system uses commodity graphics hardware and Open-GL. To evaluate the visualisation systems a task-based user test is designed and implemented. The test requires the subjects to be observed while they complete a 3D diagnostic task using each system. The speed and accuracy with which the task is performed are used as metrics. The experimental results are used to compare the effectiveness of the augmented perceptual depth cues and to cross-compare the systems. The experiments show that the user performance in the visualisation systems are statistically equivalent. This suggests that the enhanced X-ray visualisation can be used in place of CT data for some tasks. The benefits of this are two fold: a decrease in the patient's exposure to radiation and a reduction in the data acquisition time.

Character animation is the process of modelling and rendering a mobile character in a virtual world. It has numerous applications both off-line, such as virtual actors in films, and real-time, such as in games and other virtual environments. There are a number of algorithms for determining the appearance of an animated character, with different trade-offs between quality, ease of control, and computational cost. We introduce a new method, animation space, which provides a good balance between the ease-of-use of very simple schemes and the quality of more complex schemes, together with excellent performance. It can also be integrated into a range of existing computer graphics algorithms. Animation space is described by a simple and elegant linear equation. Apart from making it fast and easy to implement, linearity facilitates mathematical analysis. We derive two metrics on the space of vertices (the “animation space”), which indicate the mean and maximum distances between two points on an animated character. We demonstrate the value of these metrics by applying them to the problems of parametrisation, level-of-detail (LOD) and frustum culling. These metrics provide information about the entire range of poses of an animated character, so they are able to produce better results than considering only a single pose of the character, as is commonly done. In order to compute parametrisations, it is necessary to segment the mesh into charts. We apply an existing algorithm based on greedy merging, but use a metric better suited to the problem than the one suggested by the original authors. To combine the parametrisations with level-of-detail, we require the charts to have straight edges. We explored a heuristic approach to straightening the edges produced by the automatic algorithm, but found that manual segmentation produced better results. Animation space is nevertheless beneficial in flattening the segmented charts; we use least squares conformal maps (LSCM), with the Euclidean distance metric replaced by one of our animation-space metrics. The resulting parametrisations have significantly less overall stretch than those computed based on a single pose. Similarly, we adapt appearance preserving simplification (APS), a progressive mesh-based LOD algorithm, to apply to animated characters by replacing the Euclidean metric with an animation-space metric. When using the memoryless form of APS (in which local rather than global error is considered), the use of animation space for computations reduces the geometric errors introduced by LOD decomposition, compared to simplification based on a single pose. User tests, in which users compared video clips of the two, demonstrated a statistically significant preference for the animation-space simplifications, indicating that the visual quality is better as well. While other methods exist to take multiple poses into account, they are based on a sampling of the pose space, and the computational cost scales with the number of samples used. In contrast, our method is analytic and uses samples only to gather statistics. The quality of LOD approximations by improved further by introducing a novel approach to LOD, influence simplification, in which we remove the influences of bones on vertices, and adjust the remaining influences to approximate the original vertex as closely as possible. Once again, we use an animation-space metric to determine the approximation error. By combining influence simplification with the progressive mesh structure, we can obtain further improvements in quality: for some models and at some detail levels, the error is reduced by an order of magnitude relative to a pure progressive mesh. User tests showed that for some models this significantly improves quality, while for others it makes no significant difference. Animation space is a generalisation of skeletal subspace deformation (SSD), a popular method for real-time character animation. This means that there is a large existing base of models that can immediately benefit from the modified algorithms mentioned above. Furthermore, animation space almost entirely eliminates the well-known shortcomings of SSD (the so-called “candy-wrapper” and “collapsing elbow” effects). We show that given a set of sample poses, we can fit an animation-space model to these poses by solving a linear least-squares problem. Finally, we demonstrate that animation space is suitable for real-time rendering, by implementing it, along with level-of-detail rendering, on a PC with a commodity video card. We show that although the extra degrees of freedom make the straightforward approach infeasible for complex models, it is still possible to obtain high performance; in fact, animation space requires fewer basic operations to transform a vertex position than SSD. We also consider two methods of lighting LOD-simplified models using the original normals: tangent-space normal maps, an existing method that is fast to render but does not capture dynamic structures such as wrinkles; and tangent maps, a novel approach that encodes animation-space tangent vectors into textures, and which captures dynamic structures. We compare the methods both for performance and quality, and find that tangent-space normal maps are at least an order of magnitude faster, while user tests failed to show any perceived difference in quality between them.