Die ALS ist eine fortschreitende neurodegenerative Erkrankung, deren Symptome durch den Untergang der Motoneuronen bedingt sind. Neueste zytogenetische Untersuchungen zeigen ein vermehrtes Auftreten konstitutioneller Chromosomenveränderunge bei ALS-Patienten. Dies lässt eine Verbindung zwischen dem Ausbruch der Erkrankung und der auffälligen Zytogenetik vermuten. Das Auftreten spontaner Chromosomenveränderungen als Zeichen einer chromosomalen Instabilität wurde in der vorliegenden Arbeit an ALS-Patienten untersucht. METHODE: Neben der Karyotypisierung, der Bestimmung der SCE-Rate und der Bruchrate nach Behandlung mit Bleomycin kam die Fluoreszenz in situ Hybridisierung zum Einsatz. Die Untersuchungen wurden an Patienten mit sporadischer ALS (45), an Kontrollpersonen (38) und Verwandten (9) durchgeführt. ERGEBNISSE: Die Karyotypisierung ergab bei den Patienten eine spontane Translokationsrate von 0,02 Translokationen/Zelle (t/Z), bei den Kontrollen 0,04 t/Z. Weitere numerische oder strukturelle Auffälligkeiten waren nicht signifikant verschieden. Es wurden keine konstitutionellen Chromosomenaberrationen gefunden. Die Häufigkeit der Schwesterchromatidaustausche (SCE-Rate) bewegte sich mit 7-8 SCE/Z in der Patientengruppe innerhalb der Normwerte. Durch die Zugabe von Bleomycin in die Zellkultur stieg die Zahl der Chromatidbrüche von 0,0 auf 0,8 Brüche/Z an. Dabei zeigten die untersuchten Gruppen ähnliche Progredienzen in den Bruchraten. Mit der Fluoreszenz in situ Hybridisierung werden quantitative Aussagen über spontane Translokationsraten gemacht. Sie betrug in der Kontroll-und Patientengruppe 0,03 bis 0,04 t/Z. DISKUSSION: Die vorliegenden Ergebnisse liefern keinen Anhalt für eine chromosomale Instabilität als Risikofaktor für die Entstehung der sporadischen ALS. Indizien für eine chromosomale Instabilität wie erhöhte Bruchraten und SCEs als auch vermehrtes Auftreten somatischer Aberrationen konnten bei den ALS-Patienten nicht nachgewiesen werden. Über mögliche Auffälligkeiten in den Motoneuronen lässt sich allerdings mit den Untersuchungen an Blutlymphozyten keine hinreichend sichere Aussage machen. / Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease which is characterized by the degeneration of motor neurons. Recently, a high rate of constitutional structural chromosomal rearrangements has been reported in apparently sporadic ALS patients. It remains questionable whether or not these genomic rearrangements are caused by a chromosomal instability involved in the pathogenesis of the disease. Therefore, we performed different cytogenetic studies on chromosomal instability. METHOD: We performed chromosome analyses from patients (N=45), control subjects (N=38), and relatives (N=9) after culturing blood lymphocytes. Conventional chromosome analysis after GTG-banding, chromosomal breakage test after Bleomycin treatment, the rate of sister chromatid exchange (SCE), and whole chromosome painting were used for these analyses. RESULTS: Neither karyotyping nor whole chromosome painting revealed higher levels of structural or numerical aberrations in lymphocytes of patients with sALS. After karyotyping we found 0.02 t/cell in patients and 0.04 t/cell in controls. Whole chromosome painting revealed 0.04 t/cell in patients and 0.03 t/cell in controls. The chromosomal breaks increased likewise after Bleomycin treatment in the control group and the patient group as well. Cell cultures without Bleomycin did not show any breaks while the highest Bleomycin concentration induced up to 0.08 breaks/cell. The SCE rate in patients which corresponds to the chromatid repair activity did not rise to a higher level than in the control individuals. Both groups were in the normal range of 7 to 8 SCE/cell. DISCUSSION: The pathomechanism of neurodegeneration in ALS patients is still unknown. We tried to find a cytogenetic correlative being a risk factor for the development of ALS. However, so far there is no clue for chromosomal instability being involved in the neurodegenerative process.

La Tesis presenta el desarrollo de una metodología de análisis y diseño de sistemas distribuidos de tiempo real estricto, y su aplicación a una implementación práctica en lenguaje Ada.Se han optimizado los métodos existentes para la planificación y análisis de sistemas distribuidos de tiempo real mediante un algoritmo heurístico para la asignación de prioridades, y la aplicación del algoritmo de servidor esporádico a la planificación de redes de comunicación de tiempo real. También se ha ampliado el campo de aplicación del análisis a sistemas más complejos en los que existe sincronización por intercambio de eventos o paso de mensajes.Se ha demostrado que la metodología propuesta se puede implementar en sistemas de tiempo real prácticos, a través de su aplicación a sistemas distribuidos programados en lenguaje Ada. / The Thesis presents a methodology to analyze and design distributed real-time systems, and its application to a practical implementation.Existing methods for scheduling and analyzing distributed real-time systems have been optimized through a new heuristic algorithm for assigning priorities, and with the application of the sporadic server algorithm for scheduling real-time communication networks. The area of application of the analysis has been extended to more complex systems, like those with synchronization through event exchange or message passing.It has been demonstrated that the proposed methodology can be implemented in practical real-time systems, through the application to a distributed system programmed in the Ada language.

No description available.

No description available.

La maladie de Parkinson (MP) est une affection neurodégénérative invalidante et incurable. Il est maintenant clairement établi que d’importants déterminants génétiques prédisposent à son apparition. La recherche génétique sur des formes familiales de la MP a mené à la découverte d’un minimum de six gènes causatifs (SNCA, LRRK2, Parkin, PINK1, DJ-1 and GBA) et certains, par exemple LRRK2, contiennent des variations génétiques qui prédisposent également aux formes sporadiques. La caractérisation des protéines codées par ces gènes a mené à une meilleure compréhension des mécanismes moléculaires sousjacents. Toutefois, en dépit de ces efforts, les causes menant à l’apparition de la MP restent inconnues pour la majorité des patients. L’objectif général des présents travaux était d’identifier des mutations prédisposant à la MP dans la population canadienne-française du Québec à partir d’une cohorte composée principalement de patients sporadiques. Le premier volet de ce projet consistait à déterminer la présence de mutations de LRRK2 dans notre cohorte en séquençant directement les exons contenant la majorité des mutations pathogéniques et en effectuant une étude d’association. Nous n’avons identifié aucune mutation et l’étude d’association s’est avérée négative, suggérant ainsi que LRRK2 n’est pas une cause significative de la MP dans la population canadienne-française. La deuxième partie du projet avait pour objectif d’identifier de nouveaux gènes causatifs en séquençant directement des gènes candidats choisis à cause de leurs implications dans différents mécanismes moléculaires sous-tendant la MP. Notre hypothèse de recherche était basée sur l’idée que la MP est principalement due à des mutations individuellement rares dans un grand nombre de gènes différents. Nous avons identifié des mutations rares dans les gènes PICK1 et MFN1. Le premier code pour une protéine impliquée dans la régulation de la transmission du glutamate tandis que le second est un des acteurs-clés du processus de fusion mitochondriale. Nos résultats, qui devront être répliqués, suggèrent que le séquençage à grande échelle pourrait être une méthode prometteuse d’élucidation des facteurs de prédisposition génétiques à la MP ; ils soulignent l’intérêt d’utiliser une population fondatrice comme les canadiens-français pour ce type d’étude et devraient permettre d’approfondir les connaissances sur la pathogénèse moléculaire de la MP. / Parkinson’s disease (PD) is a complex neurological disorder with significant genetic predisposing factors which are extremely heterogeneous. Investigations of familial forms of the disorder revealed causative mutations in six different genes, namely SNCA, LRRK2, Parkin, PINK1, DJ-1 and GBA, and functional analyses of these gene products pinpointed dysfunction of key molecular pathways involved in the neurodegenerative process of the disorder. Further sequencing and genome-wide association studies indicated that some of these genes, including LRRK2, also contain variants predisposing to sporadic forms of PD. Despite these significant breakthroughs, the vast majority of PD genetic predisposing factors remain unknown. Our goal was to identify mutations predisposing to PD in the French Canadian (FC) population from a cohort mostly composed of late-onset sporadic cases. We therefore sequenced the two exons of LRRK2 that contain most of the pathogenic mutations and we performed a case-control association study. Sequencing analysis did not reveal any reported or novel mutations and the case-control association study did not provide any positive signal, thus indicating that common variants in LRRK2 are unlikely to be a significant cause of late-onset PD in the FC population. Because of the allelic and non-allelic genetic heterogeneity observed for PD, we hypothesized that dozens of genes may carry rare pathogenic mutations. The second part of this research project was therefore aimed at identifying new PD causative genes by direct sequencing of genes functionally associated with the known causative gene pathways. Our screening uncovered several rare mutations likely pathogenic in the PICK1 and the MFN1 genes. PICK1 is involved in internalization of AMPA receptors whereas MFN1 is one of the core components of the mitochondrial fusion/fission machinery. Although these observations will need to be replicated, our findings support the previously suspected pathogenic role for glutamate excitotoxicity and imbalanced mitochondrial dynamics in Parkinson’s disease. They further emphasize the value of inbred populations in genetic studies of PD and provide new clues to the molecular pathogenesis of the disorder.

Made available in DSpace on 2009-11-18T19:00:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2003 / o presente estudo de caso investiga, empiricamente, a rentabilidade associada aos consumidores do varejo eletrônico de bens duráveis no Brasil. Para tal, o arcabouço teórico baseia-se em teorias rivais, notadamente as expostas na literatura tradicional do Marketing de Relacionamento - que discute os beneficios da retenção de clientes - e nas recentes publicações que questionam tal abordagem - argumentando que os consumidores esporádicos podem se mostrar mais valiosos que os freqüentes. Nas duas empresas investigadas, os clientes esporádicos demonstram-se mais rentáveis que os freqüentes. Entretanto, a análise exploratória dos dados qualitativos demonstra que ambas utilizam abordagens transacionais para interagir com os consumidores. O cruzamento das evidências quali-quantitativas sugere que o declínio do valor dos clientes freqüentes está associado a práticas gerenciais que não se encontram em conformidade com a literatura convencional de marketing. Por conseguinte, as evidências quantitativas parecem não representar anomalias perante a teoria vigente, segundo a qual os beneficios inerentes à retenção de consumidores fazem sentido apenas para as empresas que estiverem orientadas a clientes e puderem interagir de forma relacional com os mesmos. O estudo possibilita supor que o valor dos clientes está associado à forma como as empresas se relacionam com o mercado. A adoção de práticas transacionais, a baixa diferenciação e a competição baseada em descontos parece potencializar a sensibilidade ao preço por parte dos consumidores, principalmente daqueles mais freqüentemente. / This case study investigate, empirically, the profitability associated with frequent and sporadic consumers in the Brazilian e-retailing arena of durable goods. The theoretical framework is based on rivals theories, namely the traditional relationship marketing literature - discussing the customers retention benefits - and then recent publications questioning this approach - arguing that sporadic consumers can be more valuable than frequent customers. In both of the firms, sporadic consumers generates higher profits than frequent ones. However, the exploratory analysis of qualitative data shows that firms uses transactional approach to interact with consumers. The cross-method analysis, of qualitative and quantitative evidences, suggests that the decline of frequent customers value is associated with managerial practices not in conformity with the conventional marketing literature. Therefore, the quantitative evidences seems not to represent anomalies face the dominant theory, according to which the consumers retention benefits makes sense only to companies oriented to customers, and those which interact in a relational fashion with them. The study allows to suppose the value of customers is associated with the way companies relates to the market. The adoption of transactional practices, the low differentiation, and the discount-based competition seems to increase the customer's price sensibility, mainly for those more frequent buyers.

Real time systems have been a major area of study for many years. Advancements in electronics, computers, information technology and digital networks are fueling major changes in the area of real time systems. In this thesis, we look at some of the most commonly modeled real time task systems, such as the periodic task model, including more complex task models such as the sporadic task systems. Primary focus of researchers in these fields include how to guarantee hard real time requirement of any task specification, with the minimal utilization of available hardware resources. Advancement in technology has brought multi-cored architectures with shared memory and massively parallel computing devices within the reach of ordinary computer users. Hence, it makes sense to study existing and newer task models on a wide variety of hardware platforms. Periodic task model and systems with such task models have been designed and well understood. Newer models such as the sporadic task models have been proposed to capture a more larger variety of real time systems being designed and used. We focus on designing more efficient scheduling algorithms for the sporadic LL task model, and propose simpler proofs to some of the algorithms existing in current literature. This thesis also focuses on scheduling sporadic task systems, under both multiprocessor full-migration and multiprocessor partitioned scheme. We also provide approximation algorithms to efficiently determine feasibility of such task systems.

Introduction: Sports consumption is a unique human experience in which consumers invest both money and emotions where the game becomes the main focus of the event and constitutes what is known to be a sporting event. Sports organizations are required to track how their service quality is perceived during these events in order to understand the values of their spectators and to evaluate levels of satisfaction. As prior seasons in the SHL has shown an average decreasing number of attendances at the arenas, a possible issue may exist, suggesting that further understanding about how the service is perceived becomes useful.  Purpose: The purpose of this master thesis is to examine how sporadic spectators experience the service quality offered by HV71 at Kinnarps Arena. Moreover, five dimensions within service quality are implemented to distinguish the perceived service quality among sporadic spectators in various areas, and how it relates to the intention to attend more games. Based on that, two research questions and six hypotheses were formulated for this thesis. Method: To fulfill the purpose of the study, a quantitative method was conducted. The data was collected through a survey distributed by HV71 to spectators attending at Kinnarps Arena during the 2019/2020 SHL season. Due to the quantitative method, a deductive approach became useful as hypotheses with a modified framework were developed based on an existing theory. The theoretical anchoring includes prior research in the field of service quality and how it is associated with sporting events, which has been incorporated when analyzing the empirical findings.  Conclusion: The empirical findings in this study presents how the sporadic spectator perceives the service offered at Kinnarps Arena, whereas some differences between the dimensions exist. Moreover, the findings showed that each dimension are positively related with the perceived service quality, while identifying that there is not a strong relationship between the perceived service quality and intention to attend more games. Some findings suggested that other factors contribute to the intention to attend more, and not solely the perceived service quality.

Pancreatic cancer is still a dismal disease. The high mortality rate is mainly caused by the lack of highly sensitive and specific diagnostic tools, and most of the patients are diagnosed in an advanced and incurable stage. Knowledge about precursor lesions for pancreatic cancer has grown significantly over the last decade, and nowadays we know that mainly three lesions (PanIN, and IPMN, MCN) are responsible for the development of pancreatic cancer. The early detection of these lesions is still challenging but provides the chance to cure patients before they might get an invasive pancreatic carcinoma. This paper focuses on PanIN, IPMN, and MCN lesions and reviews the current level of knowledge and clinical measures.

No description available.