The diploma thesis deals with the numerical modeling of the zip-line and its experimental verification on a small scale. An experimental zip-line is identified and then the results are compared with the numerical model outputs. The goal is to validate abilities of the numerical model in the case of simulation of a zip-line.

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This thesis investigates two main aspects of air transportation system, demand and capacity. The first study aims to estimate the potential market for Zip Vehicles, an advanced commuter type of aircraft equipped with automation and electric propulsion technologies. A Multinomial Logit Model was developed to estimate the mode choice behavior of commuters between Zip vehicle, auto and transit in seven metropolitan areas in the United States. The results showed that the Out-of-Vehicle travel time plays an important role in the decision process of commuters. Zip Vehicle is predicted to achieve residual demand with the current technologies and could become more competitive if it was equipped with Vertical Take-Off Technology. The second study developed a hybrid airport runway capacity model that blends both deterministic and simulation techniques. The model includes a graphic user interface that allows high degree of freedom to modify input parameters, such as airport information, weather conditions, minimum separation distances and aircraft grouping system. The model is widely validated and it appears to be a consistent solution for estimating airport capacity at different levels and with various degree of extensibility. / Master of Science

Ce manuscrit porte sur certaines extensions à des séries temporelles prenant des valeurs entières du modèle paramétrique périodique autorégressif établi pour des séries prenant des valeurs réelles. Les modèles que nous considérons sont basés sur l'utilisation de l'opérateur de Steutel et Van Harn (1979) et généralisent le processus autorégressif stationnaire à valeurs entières (INAR) introduit par Al-Osh & Alzaid (1987) à des séries de comptage périodiquement corrélées. Ces généralisations incluent l'introduction d'un opérateur périodique, la prise en compte d'une structure d’autocorrélation plus complexe dont l’ordre est supérieur à un, l'apparition d'innovations de variances périodiques mais aussi à inflation de zéro par rapport à une loi discrète donnée dans la famille des distributions exponentielles, ainsi que l’utilisation de covariables explicatives. Ces extensions enrichissent considérablement le domaine d'applicabilité des modèles de type INAR. Sur le plan théorique, nous établissons des propriétés mathématiques de nos modèles telles que l'existence, l'unicité, la stationnarité périodique de solutions aux équations définissant les modèles. Nous proposons trois méthodes d'estimation des paramètres des modèles dont une méthode des moments basée sur des équations du type Yule-Walker, une méthode des moindres carrés conditionnels, et une méthode du quasi maximum de vraisemblance (QML) basée sur la maximisation d'une vraisemblance gaussienne. Nous établissons la consistance et la normalité asymptotique de ces procédures d'estimation. Des simulations de type Monte Carlo illustrent leur comportement pour différentes tailles finies d'échantillon. Les modèles sont ensuite ajustés à des données réelles et utilisés à des fins de prédiction. La première extension du modèle INAR que nous proposons consiste à introduire deux opérateurs de Steutel et Van Harn périodiques, l'un modélisant les autocorrélations partielles d'ordre un sur chaque période et l'autre captant la saisonnalité périodique des données. Grâce à une représentation vectorielle du processus, nous établissons les conditions l'existence et d'unicité d'une solution périodiquement corrélées aux équations définissant le modèle. Dans le cas où les innovations suivent des lois de Poisson, nous étudions la loi marginale du processus. Á titre d'exemple d'application sur des données réelles, nous ajustons ce modèle à des données de comptage journalières du nombre de personnes ayant reçu des antibiotiques pour le traitement de maladies respiratoires dans la région de Vitória au Brésil. Comme les affections respiratoires sont fortement corrélées au niveau de pollution atmosphérique et aux conditions climatiques, la structure de corrélation des nombres quotidiens de personnes recevant des antibiotiques montre, entre autres caractéristiques, une périodicité et un caractère saisonnier hebdomadaire. Nous étendons ensuite ce modèle à des données présentant des autocorrélations partielles périodiques d'ordre supérieur à un. Nous étudions les propriétés statistiques du modèle, telles que la moyenne, la variance, les distributions marginales et jointes. Nous ajustons ce modèle au nombre quotidien de personnes recevant du service d'urgence de l'hôpital public de Vitória un traitement pour l'asthme. Enfin, notre dernière extension porte sur l'introduction d'innovations suivant une loi de Poisson à inflation de zéro dont les paramètres varient périodiquement, et sur l’ajout de covariables expliquant le logarithme de l'intensité de la loi de Poisson. Nous établissons certaines propriétés statistiques du modèle et nous mettons en oeuvre la méthode du QML pour estimer ses paramètres. Enfin, nous appliquons cette modélisation à des données journalières du nombre de personnes qui se sont rendues dans le service d'urgence d'un hôpital pour des problèmes respiratoires, et nous utilisons comme covariable la concentration de polluant dans la même zone géographique. / This manuscript deals with some extensions to time series taking integer values of the autoregressive periodic parametric model established for series taking real values. The models we consider are based on the use of the operator of Steutel and Van Harn (1979) and generalize the stationary integer autoregressive process (INAR) introduced by Al-Osh & Alzaid (1987) to periodically correlated counting series. These generalizations include the introduction of a periodic operator, the taking into account of a more complex autocorrelation structure whose order is higher than one, the appearance of innovations of periodic variances but also at zero inflation by relation to a discrete law given in the family of exponential distributions, as well as the use of explanatory covariates. These extensions greatly enrich the applicability domain of INAR type models. On the theoretical level, we establish mathematical properties of our models such as the existence, the uniqueness, the periodic stationarity of solutions to the equations defining the models. We propose different methods for estimating model parameters, including a method of moments based on Yule-Walker equations, a conditional least squares method, and a quasi-maximum likelihood method based on the maximization of a Gaussian likelihood. We establish the consistency and asymptotic normality of these estimation procedures. Monte Carlo simulations illustrate their behavior for different finite sample sizes. The models are then adjusted to real data and used for prediction purposes.The first extension of the INAR model that we propose consists of introducing two periodic operators of Steutel and Van Harn, one modeling the partial autocorrelations of order one on each period and the other capturing the periodic seasonality of the data. Through a vector representation of the process, we establish the conditions of existence and uniqueness of a solution periodically correlated to the equations defining the model. In the case where the innovations follow Poisson's laws, we study the marginal law of the process. As an example of real-world application, we are adjusting this model to daily count data on the number of people who received antibiotics for the treatment of respiratory diseases in the Vitória region in Brazil. Because respiratory conditions are strongly correlated with air pollution and weather, the correlation pattern of the daily numbers of people receiving antibiotics shows, among other characteristics, weekly periodicity and seasonality. We then extend this model to data with periodic partial autocorrelations of order higher than one. We study the statistical properties of the model, such as mean, variance, marginal and joined distributions. We are adjusting this model to the daily number of people receiving emergency service from the public hospital of the municipality of Vitória for treatment of asthma. Finally, our last extension deals with the introduction of innovations according to a Poisson law with zero inflation whose parameters vary periodically, and on the addition of covariates explaining the logarithm of the intensity of the Poisson's law. We establish some statistical properties of the model, and we use the conditional maximum likelihood method to estimate its parameters. Finally, we apply this modeling to daily data of the number of people who have visited a hospital's emergency department for respiratory problems, and we use the concentration of a pollutant in the same geographical area as a covariate. / Este manuscrito trata de algumas extensões para séries temporais de valores inteiros domodelo paramétrico periódico autorregressivo estabelecido séries temporais de valores reais. Osmodelos considerados baseiam-se no uso do operadorde Steutel e Van Harn (1979) e generalizamo processo autorregressivo depara números inteiros estacionários (INAR) introduzidos por Al-Osh & Alzaid(1987) para séries de contagem periodicamente correlacionadas. Essas generalizações incluem aintrodução de um operador periódico, a consideração de uma estrutura de autocorrelação mais complexa,cuja ordem é maior do que um, o aparecimentode inovações de variâncias periódicas, e também ainflação zero em relação a uma lei discreta dadana família de distribuições exponenciais, bem comoo uso de covariáveis explicativas. Essas extensões enriquecem muito o domínio de aplicabilidade dosmodelos do tipo INAR. No nível teórico, estabelecemospropriedades matemáticas de nossos modeloscomo a existência, a unicidade, e a estacionariedadeperiódica de soluções para as equações que definemos modelos. Propomos três métodos para estimarparâmetros de modelos, incluindo um métodode momentos baseado nas equações de Yule-Walker,um método de mínimos quadrados condicionais e ummétodo de quasi-máxima verossimilhança (QML) baseadona maximização de uma probabilidade Gaussiana. Estabelecemos a consistência e a normalidadeassintótica desses procedimentos de estimativa. Assimulações de Monte Carlo ilustram seus comportamentospara diferentes tamanhos de amostras finitas.Os modelos são então ajustados para dados reais eusados para fins de previsão. A primeira extensão domodelo INAR que propomos consiste na introdução de dois operadores periódicos de Steutel e VanHarn, o primeiro atua modelando as autocorrelações parciais de ordem um em cada período e o outro capturando a sazonalidade periódica dos dados.Através de uma representação vetorial do processo,estabelecemos as condições existência e unicidadede uma solução periodicamente correlacionada às equações que definem o modelo. No casoem que as inovações seguem as leis de Poisson,estudamos a lei marginal do processo. Como umexemplo de aplicação no mundo real, estamos ajustandoeste modelo aos dados diários de contagemdo número de pessoas que receberam antibióticos para o tratamento de doenças respiratórias na região de Vitória, Brasil. Como as condições respiratórias estão fortemente correlacionadas com a poluição doar e o clima, o padrão de correlação dos números diários de pessoas que recebem antibióticos mostra,entre outras características, a periodicidade semanale a sazonalidade. Em seguida, estendemosesse modelo para dados com autocorrelações parciaisperiódicas de ordem maior que um. Estudamosas propriedades estatísticas do modelo, como média,variância, distribuições marginais e conjuntas. Ajustamosesse modelo ao número diário de pessoascom problema respiratório que receberam atendimentode emergência no pronto-atendimento da redepública do município de Vitória. Finalmente, nossa última extensão trata da introdução de inovações de acordo com uma lei de Poisson com inflação zero cujos parâmetros variam periodicamente, e daadição de covariáveis explicando o logaritmo da intensidadeda lei de Poisson. Estabelecemos algumaspropriedades estatísticas do modelo e usamoso método QML para estimar seus parâmetros. Porfim, aplicamos essa modelagem aos dados diários sobre o número de pessoas que visitaram o departamentode emergência de um hospital por problemasrespiratórios e usamos como covariável a sérieconcentrações diárias e um poluente medido namesma área geográfica.

In der vorliegenden Arbeit wurden Experimente zur pflanzlichen Eisenassimilation durchgeführt. Zwei cDNAs aus Tomatenwurzeln (LeIRT1 und LeIRT2, GenBank Acc-Nr. AF176579 und AF176580) wurden isoliert. Sie komplementierten Fe-aufnahmedefiziente Hefestämme in Bezug auf das Wachstum auf Fe-limitierendem Medium. Die durch die LeIRT-Proteine vermittelte Fe-Aufnahme wurde in Hefezellen charakterisiert. Sie war temperaturabhängig, sättigbar und Fe2+, nicht Fe3+ wurde transportiert. Kompetitions- und Komplementationsexperimente mit metall-aufnahmedefizienten Hefemutanten legten die Vermutung nahe, daß die beiden cDNAs für Kationentransporter codieren, die eine breite Substratspezifität für Übergangsmetalle aufweisen. Die Transkripte der LeIRT-Gene konnten fast ausschließlich in Wurzeln nachgewiesen werden, wobei LeIRT1 durch Fe-Mangel induziert war, während für LeIRT2 keine Regulation durch die Fe-Ernährung der Pflanzen erkennbar war. Die Genstruktur wurde aufgeklärt (GenBank Acc-Nr. AF246266). Schwierigkeiten in der Analyse der Fe-Assimilation höherer Pflanzen machten es notwendig, einen neuen Modellorganismus zu suchen. Dabei wurde die einzellige Alge Chlamydomonas reinhardtii ausgewählt. Physiologische Studien zeigten, daß diese Alge ähnliche Fe-Mangelreaktionen wie die meisten höheren Pflanzen aufweist. Insbesondere die starke Induktion einer Fe3+-Chelatreduktase und die parallele Induktion der Fe-Transportkapazität unter Fe-Mangel waren deutlich. Mindestens zwei Fe-Transportsysteme wurden postuliert, von denen das höheraffine durch Cu-Ionen gehemmt wurde. / In the present study, experiments were conducted to analyze the iron assimilation in plants. Two cDNAs from tomato roots (LeIRT1 and LeIRT2, GenBank Acc-Nr. AF176579 and AF176580) were isolated that complemented the growth defect of Fe uptake-deficient yeast mutants. The Fe uptake mediated by the LeIRT proteins was characterized in yeast. It was temperature-dependent, saturable and Fe2+ rather than Fe3+ was transported. Competition and complementation experiments with metal uptake-deficient yeast mutants suggested that both cDNAs code for cation transporters exhibiting broad substrate specificity for transition metals. The transcripts of both genes were predominantly detected in roots, LeIRT1 being induced by Fe deficiency whereas LeIRT2 was unaffected by the Fe status of the plants. The gene structure was determined (GenBank Acc-Nr. AF246266). Problems in the analysis of Fe assimilation in higher plants made it necessary to establish a new model organism. The unicellular eucaryotic alga, Chlamydomonas reinhardtii, was chosen. Physiological studies indicated that this alga reacted to Fe deficiency similar to most higher plants. Particularly the strong induction of an Fe3+-chelate reductase paralleled by the induction of Fe transport capacitiy under Fe deficiency were evident. At least two Fe transporters were postulated, one of which was inhibited by Cu ions.

OCL1 (Outer Cell Layer 1) est le membre fondateur, chez le maïs, de la famille multigénique regroupant les facteurs de transcription HD-ZIP IV. La plupart de ces gènes s’exprime préférentiellement dans l’épiderme, et chez Arabidopsis l’étude de mutants a montré que certains HD-ZIP IV étaient essentiels pour la différenciation de cette couche cellulaire. Lors de ma thèse je me suis intéressée à la régulation du gène OCL1 par un petit ARN non codant. En effet, la conservation au sein des 3’UTR de plusieurs gènes HD-ZIP IV d’un motif de 21 nucléotides (nt) suggérait l’existence d’un tel mécanisme. J’ai mis en évidence que ce motif de 21 nt était conservé des Bryophytes aux Angiospermes et qu’il était toujours couplé à un second motif conservé d’une taille de 19 nt avec lequel il peut s’apparier pour former une structure secondaire de type tige-boucle. J’ai démontré l’existence d’un petit ARN ayant une séquence (quasi) complémentaire au site de 21 nt. La biogenèse de ce petit ARN de 24 nt que nous avons nommé small1, dépend de RDR2/ MOP1, DCL3 et Pol IV/ RMR6, composants normalement requis pour le mécanisme de RdDM. A l’aide d’un système GFP sensor, j’ai cependant mis en évidence que small1 régulait l’expression de son gène cible par inhibition de la traduction et non par RdDM. Ces expériences ont par ailleurs démontré qu’OCL1 n’est pas régulé uniquement par small1, mais également via un second mécanisme dans lequel pourrait intervenir la structure secondaire de type tige-boucle. Enfin, j’ai montré que small1 possède une extrémité 5’modifiée, expliquant ainsi son absence des banques de données et définissant aussi une nouvelle classe de petits ARN chez les plantes. / Small non-coding RNAs are versatile riboregulators that control gene expression at the transcriptional or post-transcriptional level, governing many facets of plant development and stress responses. We previously suggested the possible regulation of OCL1 (Outer Cell Layer1) by a small RNA based on the intriguing presence of two conserved motives of 19 and 21nt in its 3’UTR. ZmOCL1 is a founding member of the HD-ZIP IV gene family encoding plant specific transcription factors mainly involved in epidermis differentiation and specialization. Here we present evidence for the existence of a 24 nt small RNA complementary to ZmOCL1 3’UTR which accumulates preferentially in maize reproductive organs but also in Arabidopsis flowers and inflorescences. The biogenesis of this 24 nt small RNA (that we named small1) depends on MOP1/RDR2 and RMR6/POLIV and DCL3, components normally required for RNA-dependent DNA-methylation. Unexpectedly GFP-sensor experiments showed that small1 may regulate its target at the post-transcriptional level, mainly through translational inhibition. These experiments further highlighted the importance of additional 3’UTR sequences required for efficient target repression, possibly implicating a secondary stem-loop structure. Finally, we showed that small1 is modified at its 5’ end, which not only explains its absence from the current databases but also defines a novel class of plant small RNAs.

International Telemetering Conference Proceedings / October 25-28, 1999 / Riviera Hotel and Convention Center, Las Vegas, Nevada / The ultra high capacity disk-based data recorders now entering service offer not just a convenient and inexpensive alternative to conventional tape systems for applications like Telemetry and Flight Test but also a unique opportunity to rethink the classical models for data capture, analysis and storage. Based on ‘open architecture’ interface standards- typically SCSI-this new generation of products represents an entirely new approach to the way data is handled. But the techniques they employ are equally applicable to any SCSI storage device. This Paper discusses a range of practical scenarios illustrating how it is now possible to `mix-and-match’ recording technologies at will-disk-array, DLT, DTF, ExaByte, JAZ, ZIP, DVD, etc.- to produce an almost infinite combination of readily scaleable plug-and-play data capture, analysis and archiving solutions. The cost and reliability benefits arising from the use of standard mass-produced storage sub-systems are also considered

Zinc is the second most abundant transition metal in biological systems. This cation is required for the catalytic activity of hundreds of enzymes which mediate protein synthesis, DNA replication and cell division. Despite the central importance of zinc in cellular homeostasis, the mechanism of zinc uptake, compartmentalization and efflux is unknown. Recently, a family of proteins, called ZIP, has been shown to control zinc uptake. Mutations in one of the genes coding for these proteins (ZIP4) can lead to potentially life-threatening diseases like Acrodermatitis Enteropathica and high levels of ZIP4 have been detected in patients suffering from pancreatic cancer. Therefore our goal is to investigate the mechanism of ZIP4 transport and regulation. It was previously shown that the intracellular loop between transmembrane III and IV (M3M4) of ZIP4 is ubiquitinated in the presence of high intracellular zinc which lead to protein degradation. Our initial hypothesis was that the large intracellular domain of ZIP4 (M3M4) is a sensor which detects the intracellular concentration of zinc and regulates the surface expression of ZIP4. In order to test this hypothesis we expressed and purified the M3M4 domain to examine the ability of M3M4 to bind zinc. Our results have demonstrated that M3M4 binds zinc with a 2:1 zinc:protein stoichiometry with nanomolar affinity. We have also shown that upon binding of zinc, M3M4 undergoes a large conformational change.

The cellular prion protein (PrPC) is unique amongst mammalian proteins in that it not only has the capacity to aggregate (in the form of scrapie PrP; PrPSc) and cause neuronal degeneration, but can also act as an independent vector for the transmission of disease from one individual to another of the same or, in some instances, other species. Since the discovery of PrPC nearly thirty years ago, two salient questions have remained largely unanswered, namely, (i) what is the normal function of the cellular protein in the central nervous system, and (ii) what is/are the factor(s) involved in the misfolding of PrPC into PrPSc? To shed light on aspects of these questions, we undertook a discovery-based interactome investigation of PrPC in mouse neuroblastoma cells (Chapter 2), and among the candidate interactors, identified two members of the ZIP family of zinc transporters (ZIP6 and ZIP10) as possessing a PrP-like domain. Detailed analyses revealed that the LIV-1 subfamily of ZIP transporters (to which ZIPs 6 and 10 belong) are in fact the evolutionary ancestors of prions (Chapter 3). We were further able to demonstrate that PrPC likely emerged from a ZIP ancestor molecule nearly half-a-billion years ago via a retrotransposition event (Chapter 4). Moreover, biochemical investigations on ZIP10, as a model LIV-1 ZIP transporter, demonstrated that the ectodomain shedding of ZIP10 observed in prion-infected mice resembles a cellular response to transition metal starvation and suggested that prion disease in mice might phenocopy a transition metal starvation status (Chapter 5). These studies have opened a new angle to study prion biology in health and disease. Biochemical investigations on other LIV-1 ZIPs and attempts at the structural elucidation of the PrP-like domain of LIV-1 ZIP proteins are ongoing and have not been included in this thesis.

The cellular prion protein (PrPC) is unique amongst mammalian proteins in that it not only has the capacity to aggregate (in the form of scrapie PrP; PrPSc) and cause neuronal degeneration, but can also act as an independent vector for the transmission of disease from one individual to another of the same or, in some instances, other species. Since the discovery of PrPC nearly thirty years ago, two salient questions have remained largely unanswered, namely, (i) what is the normal function of the cellular protein in the central nervous system, and (ii) what is/are the factor(s) involved in the misfolding of PrPC into PrPSc? To shed light on aspects of these questions, we undertook a discovery-based interactome investigation of PrPC in mouse neuroblastoma cells (Chapter 2), and among the candidate interactors, identified two members of the ZIP family of zinc transporters (ZIP6 and ZIP10) as possessing a PrP-like domain. Detailed analyses revealed that the LIV-1 subfamily of ZIP transporters (to which ZIPs 6 and 10 belong) are in fact the evolutionary ancestors of prions (Chapter 3). We were further able to demonstrate that PrPC likely emerged from a ZIP ancestor molecule nearly half-a-billion years ago via a retrotransposition event (Chapter 4). Moreover, biochemical investigations on ZIP10, as a model LIV-1 ZIP transporter, demonstrated that the ectodomain shedding of ZIP10 observed in prion-infected mice resembles a cellular response to transition metal starvation and suggested that prion disease in mice might phenocopy a transition metal starvation status (Chapter 5). These studies have opened a new angle to study prion biology in health and disease. Biochemical investigations on other LIV-1 ZIPs and attempts at the structural elucidation of the PrP-like domain of LIV-1 ZIP proteins are ongoing and have not been included in this thesis.