Dans les neuroblastomes, le gène N-MYC est amplifié dans 20-25 % des cas,associé à un mauvais pronostic. Au laboratoire, nous avions préalablement montré que la dérégulation de l’expression du gène TWIST1 était corrélée à celle de N-MYC dans les neuroblastomes agressifs de stade IV avec une amplification de N-MYC (Valsesia-Wittmann et al., 2004). Au cours de ma thèse, j’ai pu mettre en évidence que les gènes TWIST1 et TWIST2 étaient régulés positivement ou négativement de façon dose dépendante par les oncoprotéines Myc. De façon intéressante, le maintien de l’expression de TWIST1 est dépendant de l’expression des protéines Myc. Ces résultats suggèrent que la dérégulation et l’amplification des oncoprotéines Myc dans les neuroblastomes N-MYC Amplifiés pourraient permettre l’induction sélective et le maintien de l’expression de l’oncogène TWIST, agissant comme facteur de survie. / The N-MYC gene is amplified in 20-25 % of human neuroblastoma, and this amplification is associated with poor clinical outcome. We previously reported aconstant deregulation of TWIST1 in synergy with N-MYC in aggressive stage IVneuroblastoma harboring N-MYC amplification (Valsesia-Wittmann et al., 2004). We demonstrated here that specifically in neuroblastoma cells, TWIST1 and TWIST2 are negatively or positively regulated depending on Myc oncoproteins dosage, thus being a putative Myc transcriptional target. We confirmed by EMSA that Myc proteins could bind TWIST1 promoter. We further highlighted TWIST1 maintenance of expression strictly Myc dependant. Therefore, we propose that deregulation and amplification of Myc oncoproteins in aggressive neuroblastoma tumors induce selective expression and maintenance of TWIST1 oncogene, responsible forapoptosis resistance

Thesis (M.S.)--North Carolina State University, 2003. / Title from PDF t.p. (viewed on Dec. 18, 2005). Includes vita. Includes bibliographical references.

Thesis (Ph. D.)--Carleton University, 1992. / Also available in electronic format on the Internet.

[pt] A modelagem Box & Jenkins (1970) para previsão de séries temporais univariadas, de acordo com a proposta inicial das autoras, é composta de quatro etapas: Indentificação de Modelos, Estimação dos Parâmetros, Testes Estatísticos para Validação do Modelo e Previsão. Dentre as etapas citadas, a Identificação de Modelos é a de maior dificuldade na utilização prática da metodologia Box & Jenkins, é baseada no uso de estimadores para as funções de autocorrelação parcial da série, não apresenta dificuldades no caso específico de modelos puros. Porém no tratamento de modelos mistos (ARMA), onde há presença das duas componentes (AR e MA), a utilização destes estimadores muitas vezes não leva a conclusões definitivas quanto à estrutura a ser considerada. Numa tentativa de diminuição da dificuldade para indentificar modelos ARMA (p, q), existem na literatura especializada várias propostas alternativas de métodos de identificação. Este trabalho se propõe a uma análise crítica de alguns métodos e dos resultados obtidos a partir destes. A análise foi concentrada nos seguintes métodos: - Função de Autocorrelação Inversa, (Cleveland, 1972) e (Chatfield, 1979); - R & S Arrays (Gray, Kelley e Mc. Intire, 1978); - Corner Method (Béguin, Gourieroux e Monfort, 1980); - Função de Autocorrelação Extendida (Tião e Tsay, 1982); - Função de Autocorrelação Parcial Generalizada (Glasbey, 1982); cujos desempenhos foram comparados entre si e com a metodologia tradicional. Foram consideradas cinco estruturas: AR(1), AR(2), MA(1), MA(2) e ARMA(1,1). Para cada estrutura foram escolhidos três modelos, utilizando como critério sua localização na região de estacionariedade / inversibilidade. Foram simuladas quinze séries para cada modelo, variando-se a semente e o nível da série, totalizando desta forma, 225 séries, que foram submetidas a cada um dos métodos em estudo e cujos resultados foram comparados e analisados. A partir dos resultados obtidos chegou-se a várias conclusões úteis na prática quanto à utilização de cada método, porém estas conclusões são apenas relativas à amostra utilizada, pois para se chegar a conclusões definitivas o tamanho da amostra deveria ser maior e critérios estatísticos de análise poderiam ser utilizadas. Dentre as conclusões obtidas destaca-se a seguinte: embora alguns métodos alternativos de identificação tenham apresentado grande melhoria em relação ao método tradicional, o problema da identificação ainda não se encontra resolvido, assim muitas das tentativas de Box & Jenkins Automáticos tornam-se sensíveis a falhar e a presença do analista torna-se necessária. / [en] The dificulty of the Box and Jenkins approach for univariante time series forecasting lies in the stage of identification. The traditional methodology based on the estimators of the autocorrelation and partial autocorrelation functions, to mixed models(ARMA), usually leads to wrong structural identification. As an attempt to solve this problem, many authors have porposed alternative identification methods. This work intends to make a critical analysis was concentrated on the following methods: - Inverse Autocorrelation Function, (Cleveland, 1972) and (Chatfield, 1979); - R&S Arrays, (Gray, Kelley and Mc. Intire, 1978); - The Corner Method, (Beguin, Gourieroux and Monfort, 1980); - Extended Autocorrelation Function (Tiao and Tsay, 1982); - General Partial Autocorrelation Function (Glasbey, 1982); their performance were compared with each other and with the traditional method. Five structures have been studied: AR(1), AR(2), MA(1), MA(2) and ARMA(1,1). For each of them three models have been chosen /considering their position in the stationary and invertible regions. Fifteen series have been simulated for each model, varying levels and their seeds, adding up to 225 series, which were submitted to each method. The results led to several conclusions, which are restricted to the sample studied; the most important was: Although some of these methods yield to better results than the traditional ones, the problem of identification is still unsolved. So, any kind of Automatic Box and Jenkins can not be recommended.

No description available.

This paper is about retail development and its impact on local and regional communities. As the Big-box phenomena continues to play out in the 21st century, planning departments across the nation have been called to action with respect to addressing negative aspects of retail development. The purpose of this paper is to examine the nature of retail, by tracing the evolving retail form and applying critical analysis to planning practices that no longer safeguard community interests in relation to retail industry initiatives. Specifically, this paper discusses issues that shape the social, economic and physical design of urban life. To that end, this paper reflects on the impact of retail and offers guidelines for resolving potential community/retail conflicts. / Master of Urban and Regional Planning

Co-polymer facade materials have recently become a popular option in the building industry as an alternative to glazing. Ethylene Tetra-Fluoro-Ethylene (ETFE) foil has been successfully used in many projects as an innovative solution to energy-conscious design challenges. In addition, the use of ETFE membrane has resulted in significant savings in cost and structural support requirements, compared with conventional glazing, due to its low weight. There is a lack of detailed published data reporting its thermal behaviour. This study focuses on the examination of heat transfer through the ETFE membrane, and more specifically heat loss and solar gains. The document examines the impact of the material on the energy use of a building, as well as thermal comfort and interior conditions. Through field-testing and computer simulations the research evaluates the material’s thermal properties to obtain results that will assist in estimating the suitability of ETFE foil use in comparison to glass. Field-testing is used to perform a comparison of the thermal and energy behaviour of a fritted double ETFE cushion to a double glazed cover. The two experimental devices under examination present nearly identical energy consumption due to heating requirements. The experimental findings are implemented in Integrated Environmental Solutions (IES) and used to identify the necessary steps to accurately reproduce the thermal and energy behaviour associated with both covering materials. Further simulations were undertaken to provide a comparison of several types of ETFE cushions to various types of double glass. More specifically, the types examined are a clear double ETFE roof cover and a fritted double ETFE roof cover in comparison to a standard double glazed roof and a low-E double glazed roof. The roofs covers are examined in relation to energy requirements for both the heating and cooling of a space. Such an assessment of performance will provide information for further investigation to improve the material’s features and optimise energy performance.

Determining the optimal terminal box airflow is a complex process which is influenced by various factors, such as weather condition, supply air temperature, primary air fraction and internal load. A guideline for determination of a cost efficient minimum airflow setpoint for VAV terminal box units is drawn in this research. The most efficient optimal minimum airflow setpoint should not be a fix setting, but should be changing with zone load and ventilation requirement. A fixed minimum airflow is used in conventional control strategies. The terminal box minimum airflow required is not a constant since the supply air temperature, fresh air fraction and zone load are different. It is important to set up the minimum airflow to ensure IAQ and thermal comfort and to minimize energy consumption. Analysis has been carried out to compare how the supply air temperature, fresh air fraction and zone load affect the minimum airflow setting of an exterior zone. And 30% of design airflow is not always a good number, and may cause comfort issue or ventilation problem. If the minimum airflow is set higher than required, terminal boxes will have significantly simultaneous heating and cooling, and consume more fan power in the AHUs. If the minimum airflow is set lower than required, indoor air quality (IAQ) will be a concern. Energy saving ratio study is conducted to estimate the energy saving benefit by implementing an optimized minimum airflow.

Structured RNAs and RNA-protein complexes (RNPs) are involved in many essential biological processes and the specific conformations of these RNAs are crucial to their various functions. However, in vitro studies have found that RNA has propensity for misfolding into inactive species that often consist of extensive secondary and tertiary interactions, which can be locally and globally stabilizing, resulting in long-lived non-native conformers. DEAD-box helicases are one class of proteins that have been found to accelerate folding and rearrangements of highly structured RNAs. While these proteins have been shown to use ATP to unwind short RNA helices, it is not known how they disrupt the tertiary interactions that often stabilize both native and misfolded RNA conformations. We used single molecule fluorescence to probe the mechanism by which DEAD-box proteins facilitate global unfolding of a structured RNA. DEAD-box protein CYT-19, a mitochondrial protein from Neurospora crassa, was found to destabilize a specific tertiary interaction with the Tetrahymena group I intron ribozyme using a helix capture mechanism. The protein molecule binds to a helix within the structured RNA only after the helix spontaneously loses its tertiary contacts, and then uses ATP to unwind the helix, liberating the product strands. Ded1, a multi-functional DEAD-box protein found in Saccharomyces cerevisiae, gives analogous results with small but reproducible differences that may reflect its in vivo roles. The requirement for spontaneous dynamics likely targets DEAD-box proteins toward less stable RNA structures, which are likely to experience greater dynamic fluctuations, and provides a satisfying explanation for previous correlations between RNA stability and CYT-19 unfolding efficiency. Biologically, the ability to sense RNA stability probably biases DEAD-box proteins to act preferentially on misfolded structures and thereby to promote native folding while minimizing spurious interactions with stable, natively-folded RNAs. In addition, this straightforward mechanism for RNA remodeling does not require any specific structural environment of the helicase core and is likely to be relevant for DEAD-box proteins that promote RNA rearrangements of RNP complexes including the spliceosome and ribosome. / text

No description available.