Spinocerebellar ataxia type 7 (SCA7) is a hereditary neurodegenerative disorder affecting the cerebellum, pons and retina. SCA7 patients present with gait ataxia and visual impairment as the main symptoms. Anticipation, commonly observed in SCA7 families, is a phenomenon where an earlier age at onset and a more severe progression of disease is seen in successive generations. In order to identify the gene responsible for SCA7, we performed linkage analysis on a Swedish SCA7 kindred. Evidence for linkage of the SCA7 disease locus to a 32 cM region on chromosome 3p12-21.1, between markers D3S1547 and D3S1274, was established. A number of neurodegenerative disorders associated with anticipation are caused by expanded (CAG)n repeats in their respective disease genes. In order to isolate the SCA7 disease gene we, therefore, screened a human infant brain stem cDNA library for CAG repeat containing clones, mapping to chromosome 3. Four candidate clones were isolated and analysed, but could all be excluded as the SCA7 disease gene. In 1997, the SCA7 disease gene was identified and, as expected, shown to harbour a CAG repeat, expanded in SCA7 patients. Analysis of the SCA7 CAG repeat region in Swedish SCA7 patients demonstrated that CAG repeat size was negatively correlated to age at onset of disease. Furthermore, patients with larger repeats presented with visual impairment, whereas patients with smaller repeats presented with ataxia as the initial symptom. SCA7 is the most common autosomal dominant cerebellar ataxia in Sweden and Finland, but rare in other populations. In order to investigate if the relatively high frequency of SCA7 in these countries is the result of a founder effect in the region, a haplotype analysis was performed on all SCA7 families available. All 7 families shared a common haplotype of at least 1.9 cM surrounding the SCA7 locus. In addition, strong linkage disequilibrium was demonstrated for marker D3S1287 closely linked to the SCA7 gene, suggesting a founder effect for the SCA7 mutation in Sweden and Finland. The function of the SCA7 protein, ataxin-7, is not known and it does not show significant homologies to any previously known proteins. In order to gain insight into the function of ataxin-7 we analysed the expression of ataxin-7 in brain and peripheral tissue from SCA7 patients and controls. In brain, expression was found to be mainly neuronal with a nuclear subcellular localisation. Ataxin-7 expression was found throughout the CNS, not restricted to sites of pathology. We also confirmed previously reported findings of neuronal intranuclear inclusions (NIls) in the brains of SCA7 patients. Based on our findings, we conclude that the cell type specific neurodegeneration in SCA7 is not due to differences in expression pattern in affected and non-affected tissue or the distribution pattern of aggregated protein.

In this thesis, situations were analyzed in which drivers operate infotainment systems (IVIS) while driving. In this, the focus lay on such situations in which drivers operated these secondary tasks successfully. Following that, a resource orientated approach was chosen in contrast to the focus of many other studies. Demonstrating the negative effects of secondary tasks while driving was less central in this thesis. Rather, everyday behavior adaptations were analyzed that enabled drivers to operate secondary tasks successfully while driving. Therefore these adaptations were measured with regards to the following three factors: driving task, secondary task and mental workload. Additionally the influence of several secondary task attributes was analyzed. Thereby especially the perceived interruptibility was researched in detail. The thesis contains 3 different parts: 1. Introduction to research field, 2. Empiric part and 3. Overall discussion. In the first part an introduction and an overview of the current research concerning secondary task operation while driving is presented. The second part contains 3 studies, each presented in manuscript form. The goal of the first study was to show basic behavior adaptations in a driving simulator study that enables drivers to operate secondary tasks while driving. Thereby it became obvious that drivers adapted their driving behavior as well as their activity in the secondary task dynamically to the specific situation. The driving task was prioritized thereby. The adaptations were dependent on the current as well as the anticipated development of the situations and correspondingly sensitive to the variation of a cue to a hazardous driving situation. If drivers were warned (and thereby an anticipation was possible), they reduced especially their activity in the secondary task. In the second study the influence of mental workload and the attributes of a secondary task were analyzed in-depth. Drivers were informed by a noise signal either about an upcoming unknown driving situation or about an upcoming speed reduction situation in this study. It could be shown that if a secondary task can be interrupted without a perceived decline in performance, it is interrupted in demanding driving situations. If an interruption causes a perceived performance loss, the task is interrupted less often, and so the workload is increased (measured with a physiological measurement). Thus, drivers compensate their current demands by behavior adaptations in different factors, depending on the characteristics of a secondary task. The interaction between driving task, secondary task and workload could be proven by this research. Only if a secondary task could be interrupted without a perceived loss of performance drivers interrupted the task before a hazardous situation was reached. In line with the findings from the studies above a setting was developed for the third study that is less bound to the simulation of complex driving situations and thereby independent from specific driving simulator settings. Nevertheless the anticipation of further driving situations and the option to adapt behavior was given to the drivers by the setting to measure the effects described above. Additionally secondary tasks were analyzed that have a high comparability to common IVIS. Thus, a focus was on the influence of tasks that require time critical inputs. As expected, in tasks with time critical inputs the activity was less often reduced, even if a demanding driving situation was announced. Thereby another influencing factor to the perceived interruptibility of secondary tasks could be analyzed. In the presented studies it was shown that drivers anticipate the further development of a situation and adapt their activity in the secondary task dynamically due to several characteristics of this task. For the future evaluation of IVIS, methodological requirements were deduced from the presented studies and a possible setting for further research was discussed. / In dieser Dissertation werden Situationen untersucht, in denen Fahrer während der Fahrt Infotainmentsysteme (In- Vehicle Infotainment Systeme, kurz IVIS) bedienen. Hierbei wird der Fokus auf Situationen gelegt, in denen Fahrer erfolgreich Nebenaufgaben bearbeiten. Im Gegensatz zu einer Vielzahl von anderen Studien wird hier ein ressourcenorientierter Ansatz gewählt. Im Mittelpunkt steht demnach weniger der Nachweis von Leistungseinbußen in der Fahraufgabe durch zusätzliche Aufgaben. Es wird im Gegensatz dazu herausgearbeitet, durch welche alltäglichen Verhaltensanpassungen Fahrer in der Lage sind, Aufgaben zusätzlich zur Fahraufgabe erfolgreich zu bearbeiten. Dazu werden diese Verhaltensanpassungen messbar gemacht. Ein Hauptaugenmerk wird dabei auf die Faktoren Fahraufgabe, Nebenaufgabe und die mentale Beanspruchung gelegt. Des Weiteren wird der Einfluss verschiedener Nebenaufgaben auf das Verhalten analysiert. Dabei wird insbesondere die wahrgenommene Unterbrechbarkeit der Nebenaufgaben detailliert untersucht. Die Arbeit besteht aus 3 Teilen: 1. Hintergrund des Forschungsfeldes, 2.Experimentalteil und 3. zusammenfassende Diskussion. Im ersten Teil der Arbeit wird zunächst eine Einführung in das Forschungsfeld gegeben und anschließend ein Überblick über den aktuellen Forschungsstand in Bezug auf Zweitaufgabenbearbeitung während der Fahrt. Im Experimentalteil werden 3 Studien präsentiert, die im Rahmen dieser Arbeit durchgeführt wurden (jeweils in Form einer Veröffentlichung). In der ersten Studie war das Ziel grundlegende Verhaltensanpassungen in einer Fahrsimulationsstudie nachzuweisen, die es Fahrern ermöglichen Nebenaufgaben erfolgreich während der Fahrt zu bearbeiten. Dabei wurde deutlich, dass Fahrer ihr Fahrverhalten und ihre Eingabeaktivität in einer Nebenaufgabe der jeweiligen Situation dynamisch anpassen. Die Fahraufgabe wurde dabei priorisiert. Die Verhaltensanpassungen waren sowohl abhängig von der aktuellen, als auch von der antizipierten Situation und zeigten sich demnach abhängig von der Variation eines Hinweisreizes auf eine kritische Verkehrssituation. Als die Fahrer vor einer möglichen Gefahr gewarnt wurden (sie diese also antizipieren konnten), wurde insbesondere die Aktivität in der Nebenaufgabe reduziert. In der daran anschließenden Studie wurde die Rolle der Beanspruchung im Zusammenhang mit den Eigenschaften der Nebenaufgabe näher untersucht. Probanden wurden mithilfe eines Tons entweder auf eine bevorstehende, unbekannte Fahrsituation oder auf eine bevorstehende Geschwindigkeitsreduktion hingewiesen. Es konnte gezeigt werden, dass Fahrer in Situationen, in denen sie den weiteren Fahrverlauf antizipieren und die Nebenaufgabe ohne wahrgenommenen Leistungsverlust unterbrechen konnten, signifikant weniger bedienten. Im Gegensatz dazu zeigte sich in Nebenaufgaben, deren Unterbrechung einen direkten Leistungsverlust nach sich zog, dass Fahrer auch in kritischen Situation gleich viel bedienten. Dieses Verhalten wurde durch eine höhere Anstrengung kompensiert (gemessen mit einem physiologischen Beanspruchungsmaß). Der Zusammenhang der drei Faktoren Fahraufgabe, Nebenaufgabe und Beanspruchung wurde hierbei deutlich. Des Weiteren konnte der Einfluss der Eigenschaften der Nebenaufgaben deutlich gemacht werden: Nur wenn die Unterbrechung der Nebenaufgabe keinen direkten Leistungsverlust zur Folge hatte, wurde diese bereits vor dem Auftreten einer kritischen Situation unterbrochen. Basierend auf den Ergebnissen der ersten beiden Studien wurde für die dritte Studie ein vereinfachtes Setting entwickelt, das weniger auf der Simulation komplexer Fahrsituationen basiert, mithilfe dessen jedoch dennoch die relevanten Effekte messbar sein sollen. Dadurch wird das Setting unabhängiger von einer bestimmten Simulationsumgebung. Dabei wurde den Probanden sowohl ermöglicht relevante Fahrsituationen zu antizipieren als auch ihr Verhalten daran anzupassen. Des Weiteren wurden Nebenaufgaben analysiert, die ähnliche Bedieneingaben erforderten wie gebräuchliche IVIS, und die zum Teil zeitkritische Eingaben erforderten. Wenn Eingaben zeitkritisch gemacht werden mussten, wurde die Nebenaufgabe erwartungsgemäß seltener unterbrochen, auch wenn eine kritische Fahrsituation angekündigt wurde. Dadurch wurde ein weiterer Einflussfaktor auf die wahrgenommene Unterbrechbarkeit von Aufgaben in Fahrsituationen untersucht. In den vorliegenden Studien konnte gezeigt werden, dass Fahrer den weiteren Verlauf von Fahrsituationen antizipieren und ihre Aktivität in einer Nebenaufgabe dynamisch und in Abhängigkeit zu bestimmten Eigenschaften der Nebenaufgabe anpassen. Für die zukünftige Bewertung von IVIS wurden dabei relevante methodische Rahmenbedingungen herausgearbeitet und ein mögliches Setting vorgestellt.

<p>Background: Forecasting is an instrument that the managers rely upon for their anticipations of the future. Subcontractors control their operations according to the forecast volumes provided by the telecom mobile network equipment suppliers. The information in the forecasts is however not sufficient. </p><p>Purpose: The purpose of this thesis is to identify and test relevant and available market indicators for prediction of future demand fluctuations on the telecom mobile network equipment market. </p><p>Realisation: During a number of interviews, factors that are driving the network equipment market were clarified. The aim of this part was to identify possible market indicators. Hypotheses were set up to test the chosen indicators. In the second part, the indicators were tested statistically. Finally, the theoretical and logical support of the results was discussed. </p><p>Result: To predict future movements in network equipment demand, the market indicators should focus on the telecom mobile operators, and their ability, need, and willingness to make new investments. The market indicators proven to be of most importance after the regression analyses were long-term market interest rates and telecom corporate bond indices.</p>

Le contrôle de stabilité est un sujet essentiel dans les systèmes avancés d'aide à la conduite développés par les constructeurs et équipementiers automobiles. Les systèmes de sécurité actifs sont devenus un standard dans les véhicules particuliers, tels que : le contrôle électronique de la stabilité (ESC) et le système de contrôle de traction (TCS). La description du comportement dynamique du véhicule pendant le mouvement, est fondamental dans le fonctionnement des nouveaux systèmes de sécurité active. Certains systèmes actifs sont déjà implémentés dans des véhicules standards comme des options supplémentaires, pour améliorer la sécurité sur la route ou pour le confort du conducteur et des passagers. Cependant, ces systèmes ont besoin d'informations sur la dynamique de véhicule, qui représente les caractéristiques de mouvement du véhicule sur la route. L'accès à ces informations est souvent difficile, pour des raisons technologiques ou économiques. De ce fait, nous développons des algorithmes, basés sur la technique d'observation d'état, pour estimer une partie de ces variables notamment, les efforts dynamiques du contact pneumatique/chaussée et l'angle de dérive dans son environnement. En revanche, ces systèmes sont conçus pour faire face à l'état actuel du véhicule où la situation de danger a toujours eu lieu, la capacité de ces systèmes est limitée à minimiser les effets de danger. L'objectif ultime est de prévoir et d'éviter efficacement un accident avant qu'il se produise. Par conséquent, ce travail est dédié aussi à développer une méthode de prédiction des risques pour rappeler au conducteur la vitesse de sécurité pour négocier les virages à venir. Dans un premier temps, nous développons dans ce mémoire une nouvelle approche pour estimer la répartition de la charge verticale sur chaque roue dans un environnement réel. L'influence de l'angle de pente est considérée dans la phase de reconstruction du modèle du véhicule. Les forces verticales sont estimées en utilisant un filtre de Kalman. Afin d'estimer la force latérale du pneu, un filtre de Kalman entendu et un filtre Particulaire ont appliqués pour tenir compte des non-linéarités du modèle de véhicule. Deux techniques différentes d'observateurs sont proposées et comparées avec des données expérimentales. Dans un deuxième temps, nous étendons, à l'instant futur, la prise en compte de l'évaluation de risque d'accidents. La prédiction des paramètres de la dynamique du véhicule, l'évaluation du risque potentiel ainsi que la détermination d'une vitesse d'alerte à l'approche des virages, sont introduites pour réduire le risque potentiel d'accident dans les virages. Enfin, la dernière partie du mémoire est consacrée à l'application en temps réel, sur un véhicule démonstrateur, du processus d'observation d'état développé précédemment. Les résultats expérimentaux sont réalisés pour démontrer la performance des estimateurs intégrés en temps réel.

The purpose of this study was to examine whether the feedback schedule controlled by the learner created an optimal environment for retention of motor skills. Two experiments were conducted and participants were randomly assigned to a Control (100% KR), 20% RF KR, Self-controlled and Yoked conditions. In experiment one an anticipation timing task and in experiment two a ball throwing task was used. The second experiment also included a transfer test in order to measure the persistence of the acquired capability for performance. Absolute constant error (&amp / #9474 / CE&amp / #9474 / ) and variable error (VE) were calculated for four blocks of ten trials in acquisition phase and two blocks of ten trials in retention and transfer phases to analyze the subject&rsquo / s performances by repeated measures ANOVA. Experiment one analysis indicated significant main effects for groups in &amp / #9474 / CE&amp / #9474 / and VE. Participants in the self-controlled condition performed significantly better on retention test than the control group. Contrary to the expectations, experiment two analysis showed no significant differences between the groups in acquisition and retention tests. Group differences were only observed in transfer test between the 20% RF KR and Yoked conditions. There was an improvement in the performance by groups as they progressed through the acquisition trials. The results of the experiment were not consistent with regard to effects of KR on learning. The reasons might be attributed to several factors such as the age and the motivation of the subjects, and the nature of the task.

Es considera que la cognició biològica fa servir mecanismes com la predicció, l'anticipació i l'atenció per resoldre tasques complexes. S'ha suggerit que aquests mecanismes es materialitzen en els mamífers a través d'interaccions entre les capes corticals, mentre que la seva manifestació en cervells relativament més simples, como el dels invertebrats, és encara poc clara. En la cognició artificial, la naturalesa i la interacció dels mecanismes mencionats roman, en gran mesura, no quantificada. Aquí proposem un enfoc filogènic i basat en models per descobrir com interactuen aquests mecanismes cognitius. Comencem amb el model simple del cervell d'un insecte i demostrem la necessitat dels anomenats forward models per explicar el comportament d'un insecte a escenaris dinàmics. Llavors proposem el marc PASAR per integrar i quantificar la interacció dels mencionats components de la cognició. Validem el PASAR en tasques robòtiques i en un experiment psicofísic humà, demostrant que el PASAR és una eina valuosa per modelar i avaluar la cognició biològica i per construir sistemes cognitius artificials. / Biological cognition is thought to employ mechanisms like prediction, anticipation and attention for solving complex tasks. These mechanisms are suggested to be materialized through inter-layer cortical interactions in mammals, whereas their manifestation in relatively simpler brains, like the invertebrate brain, remains unclear. In artificial cognition, the nature and interplay of the above mechanisms remain largely unquantified. Here we propose a phylogenic, model-based approach to answer how these cognitive mechanisms interplay. We start with a simple model of the insect brain and demonstrate the necessity of the so-called forward models to account for insect behavior in dynamic scenarios. We then propose the PASAR framework to integrate and quantify the interplay of the above components of cognition. We validate PASAR in robotic tasks and in a human psychophysical experiment, proving PASAR as a valuable tool to model and evaluate biological cognition and to construct artificial cognitive systems.

Exquisite visually-guided movements underpin expertise in fast interceptive sports. The assumption that skilled performance relies on superior visual skills has been challenged by studies of sporting expertise which typically advocate vision to be a poor predictor of sporting success. This discordance is addressed in this thesis by examining whether visual degradation (in the form of blur) affects the performance of an interceptive action where successful execution demands precise spatial and temporal visual-motor control. The vision of skilled cricket batters was blurred using contact lenses (four increasing levels: plano, +1.00, +2.00, +3.00) in each of two experimental phases. In the first phase batters faced a bowling-machine and in-situ bowlers to examine the effect of blur on bat-ball interception. The highest level of blur (+3.00) was required to produce a significant decrease in batting performance when facing the bowling-machine at medium-paced ball-velocities (105-115 kph). A similar effect of blur was found when facing in-situ bowlers of comparable ball-velocity, however performance was found to be affected by a lower level of blur (+2.00) for faster-paced ball-velocities (120-130 kph). The +1.00 blur was concluded even at this higher ball-velocity to have no measurable effect on interceptive performance in a natural setting. The second phase sought to investigate the effect of blur on anticipation: a perceptual skill established to be an important component of expertise in many interceptive sports. It was established, using temporal occlusion of a bowling sequence, that optimal anticipation required an opportunity for bat-ball interception (facilitating close coupling between perception and action). Coupled anticipation demonstrated velocity-dependent resilience to blur; +3.00 and +2.00 were required for respective decreases in the anticipation of action-sequences for medium- and fast-paced ball-velocities. Remarkably, results suggest that blur may enhance uncoupled (verbal) anticipation according to the movement velocity of the bowler. Experimental results led to the conclusion that clear vision is not necessarily required for optimal interceptive performance, even when the demanding spatio-temporal task simulates the conditions experienced at the highest levels of competition. Results are interpreted based on the predictions of the dual-pathway theory of vision, including differences in the underlying visual information processed via these pathways.

Exquisite visually-guided movements underpin expertise in fast interceptive sports. The assumption that skilled performance relies on superior visual skills has been challenged by studies of sporting expertise which typically advocate vision to be a poor predictor of sporting success. This discordance is addressed in this thesis by examining whether visual degradation (in the form of blur) affects the performance of an interceptive action where successful execution demands precise spatial and temporal visual-motor control. The vision of skilled cricket batters was blurred using contact lenses (four increasing levels: plano, +1.00, +2.00, +3.00) in each of two experimental phases. In the first phase batters faced a bowling-machine and in-situ bowlers to examine the effect of blur on bat-ball interception. The highest level of blur (+3.00) was required to produce a significant decrease in batting performance when facing the bowling-machine at medium-paced ball-velocities (105-115 kph). A similar effect of blur was found when facing in-situ bowlers of comparable ball-velocity, however performance was found to be affected by a lower level of blur (+2.00) for faster-paced ball-velocities (120-130 kph). The +1.00 blur was concluded even at this higher ball-velocity to have no measurable effect on interceptive performance in a natural setting. The second phase sought to investigate the effect of blur on anticipation: a perceptual skill established to be an important component of expertise in many interceptive sports. It was established, using temporal occlusion of a bowling sequence, that optimal anticipation required an opportunity for bat-ball interception (facilitating close coupling between perception and action). Coupled anticipation demonstrated velocity-dependent resilience to blur; +3.00 and +2.00 were required for respective decreases in the anticipation of action-sequences for medium- and fast-paced ball-velocities. Remarkably, results suggest that blur may enhance uncoupled (verbal) anticipation according to the movement velocity of the bowler. Experimental results led to the conclusion that clear vision is not necessarily required for optimal interceptive performance, even when the demanding spatio-temporal task simulates the conditions experienced at the highest levels of competition. Results are interpreted based on the predictions of the dual-pathway theory of vision, including differences in the underlying visual information processed via these pathways.

Previous research has shown that orienting attention in time can help to improve behavioural outcomes. However, the extent to which temporal orienting can be preserved in ageing and in the context of neurological disorders remains unresolved. This thesis therefore explores temporal expectations in the healthy ageing and diseased brain by taking a neuropsychological approach. To begin, I provide an overview of the literature in <b>Chapter 1</b> most relevant for the following investigation. Four chapters of experiments then follow. To examine the effects of ageing on temporal expectation, the performance of healthy young adults and healthy older adults is presented and the results are discussed in <b>Chapter 2</b> and <b>3</b>. Though it had been previously shown that older adults seem to experience an expectation deficit on temporal expectation tasks, these chapters demonstrate the preservation of temporal expectation in ageing. On their own, these findings represent an important and novel contribution to the literature; however, this research is incapable of establishing the causal mechanisms involved in temporal expectation. To explore the causal role of relevant brain regions in temporal expectation, <b>Chapter 4</b> and <b>5</b> investigate the effects of temporal orienting in participants with damage to the basal ganglia - a brain region strongly implicated in temporal processing. In <b>Chapter 4</b>, the role of the basal ganglia in temporal expectations is examined using data collected from participants with Parkinson's disease and contrasts their performance with age-matched healthy controls. To complement this investigation, and to provide converging evidence for the basal ganglia's role in temporal expectations, Chapter 5 investigates the behavioural performance of individuals with focal lesions to the basal ganglia. The findings in this thesis are discussed in their wider context in Chapter 6, and directions for future research are proposed.

[pt] A eficiência com que uma empresa é capaz de produzir seus produtos é fundamental para sua sobrevivência em mercados cada vez mais competitivos. A presente dissertação apresenta uma proposta de minimização dos custos de produção e estoques para a otimização das decisões de Planejamento e Controle de Produção. O problema consiste em analisar as compensações entre estoque de antecipação e a contratação de pessoal adicional e/ou horas extras para suprir a demanda em momentos de pico. O objetivo é avaliar os trade-offs existentes entre os custos de hora extra e de estoques para reagir em períodos de oscilação de demanda, com o objetivo de criar um modelo de apoio à decisão de gestão da produção. Um estudo de caso é apresentado para um produto de varejo do ramo farmacêutico. O caso foi modelado por programação matemática linear e programado em sistema AIMMS. A partir dos resultados encontrados, verificou-se que com a implantação do modelo foram obtidas soluções balanceadas, com a otimização dos recursos da produção, que permite a empresa planejar antecipadamente as suas operações de maneira a minimizar os investimentos em estoques e os custos de utilização de hora-extra em termo de famílias de produtos. / [en] The ability of a company to produce their products is essential for their survival in increasingly competitive markets. The present work proposes to minimize the production and inventory costs in order to optimize the production planning and control system decisions. The problem consists in understanding the benefits between anticipation inventory and employment levels and/or overtime in order to reach non-constant, time varying demand, considering fixed sale and production capacity. We create a mixed linear programming (MLP) model to support the decisions and adjustments in planning process and production management. This study applies to a specific retail product of a pharmaceutical industry and is implemented in the AIMMS modeling language. From the results, we can say that the implementation of this model is very useful and can help to find better solutions and improve the optimization of resources, which allows the company to anticipate its decisions and minimize the investments in inventories and costs of using overtime in terms of product families.