Acquired data from dynamic contrast enhanced MRI measurements can be used to non-invasively assess tumour vascular characteristics through pharmacokinetic modelling. The modelling requires an arterial input function which is the concentration of contrast agent in the blood reaching the volume of interest as a function of time. The aim of this work is testing and optimizing a turboFLASH sequence to appraise its suitability for measuring the arterial input function by measuring phase. Contrast concentration measurements in a phantom were done with both phase and relaxivity techniques. The results were compared to simulations of the experiment conditions to compare the conformance. The results using the phase technique were promising, and the method was carried on to in-vivo testing. The in-vivo data displayed a large signal loss which motivated a new phantom experiment to examine the cause of this signal reduction. Dynamic measurements were made in a phantom with pulsatile flow to mimic a blood vessel with a somewhat modified turboFLASH sequence. The conclusions drawn from analyzing the data were used to further improve the sequence and this modified turboFLASH sequence was tested in an in-vivo experiment. The obtained concentration curve showed significant improvement and was deemed to be a good representation of the true blood concentration. The conclusion is that phase measurements can be recommended over relaxivity based measurements. This recommendation holds for using a slice selective saturation recovery turboFLASH sequence and measuring the arterial input function in the neck. Other areas of application need more thorough testing.

Abstract Magnetic resonance imaging (MRI) provides methods to study the microstructure and functional properties of tissues that can be utilized to acquire information about the degenerative processes in the spine. The purpose of the current study was to evaluate the value of diffusion-weighted MRI and quantification of delayed gadolinium enhancement in assessing intervertebral disc degeneration. An experimental degeneration model was used to evaluate the sensitivity of diffusion-weighted MRI and T2 relaxation time measurements in detecting early degenerative changes in the disc. In six pigs, an annular disc lesion was induced surgically, after which the discs were repeatedly MR imaged for up to eight weeks. T2 relaxation time of the lesioned discs decreased postoperatively, whereas apparent diffusion coefficient (ADC) initially increased, but at eight weeks decreased when compared to the control discs. The value of ADC in degeneration of human discs was evaluated by imaging 228 voluntary middle-aged men. ADC values of the three lowest lumbar intervertebral discs were measured and disc degeneration was visually graded. The reduction in ADC between visually normal and moderately degenerated discs was 4%, whereas severely degenerated discs showed 5% higher ADC values than normal discs. T2 signal intensity of the discs was significantly correlated with the ADC values. Because of a considerable overlap between ADC values of normal and degenerated discs the clinical relevance of the ADC measurements of lumbar intervertebral discs remains questionable. A method to quantify delayed enhancement of the nucleus pulposus after intravenous gadolinium contrast agent injection was developed to evaluate the diffusion of small solutes into the disc. Twenty male volunteers were imaged in order to correlate the measured change in the T1 relaxation rate with visually evaluated degenerative changes. The percentual change of T1 relaxation rate for individual discs was up to 126%, and a positive trend was observed between the delayed enhancement and the disc degeneration grades. In order to study the factors that determine the intensity of delayed enhancement, T1 relaxation rate measurements were further correlated with lumbar artery stenosis, bone marrow changes adjacent to endplates, endplate defects, and ADC of the disc. Lumbar artery stenosis and ADC values of the discs were not correlated with enhancement, while disc space narrowing and the presence of degenerative endplate changes had a strong correlation, suggesting an important role for the endplate in maintaining the integrity of the disc.

Une des principales limites de la chimiothérapie du cancer est le manque de sélectivité des agents cytotoxiques vis-à-vis des cellules tumorales, entrainant de nombreux effets secondaires. L’intérêt de la vectorisation est d’administrer l’agent cytotoxique sélectivement aux cellules cancéreuses et ainsi d’éviter de faire subir l’action du médicament aux cellules saines. Cette thèse a pour but de synthétiser des prodrogues multivalentes qui utilisent la sous unité B de la toxine de Shiga (STxB) comme agent de vectorisation, ciblant préférentiellement les cellules cancéreuses Gb3-positives. Les deux agents cytotoxiques choisis, un dérivé de la camptothécine et de l’auristatine, ont été liés de façon covalente auvecteur via un espaceur bifonctionnel clivable par le glutathion. L’espaceur a également été remplacé par un répartiteur multivalent susceptible de délivrer une quantité plus importante d’agent cytotoxique à l’intérieur des cellules tumorales.Parallèlement à ce projet de vectorisation d’un agent thérapeutique, des sondes IRM capables de marquer in vivo les tumeurs possédant à leur surface le récepteur Gb3 ont été synthétisées. L’IRM a une très bonne définition spatiale, mais souffre d’un manque de sensibilité. Pour augmenter le contraste, nous avons utilisé une stratégie reposant sur lamultivalence des espaceurs liés à des molécules de DOTA-Gd, un agent de contraste classiquement utilisé en IRM. Ces dernières ont été fixées à STxB via un répartiteur multivalent (des nano-bâtonnets d’or). Le signal IRM est plus intense et donc plus facile à détecter. Enfin, nous avons développé une nouvelle méthode chimique basée sur la ligationoxime pour optimiser la création de conjugués entre STxB et des antigènes comme outils de vaccination. Le conjugué STxB-ovalbumine a permis une meilleure présentation de l’antigène par les cellules dendritiques, conduisant chez la souris à une induction efficace de lymphocytes T. / Pas de résumé en anglais

The prime objectives of contrast agents in Magnetic Resonance Imaging(MRI) is to accelerate the relaxation rate of the solvent water protons in the surrounding tissue. Paramagnetic relaxation originates from dipole-dipole interactions between the nuclear spins and the fluctuating magnetic field induced by unpaired electrons. Currently Gadolinium(III) chelates are the most widely used contrast agents in MRI, and therefore it is incumbent to extend the fundamental theoretical understanding of parameters that drive the relaxation mechanism in these complexes. Traditionally the Solomon-Bloembergen-Morgan equations have been utilized to describe relaxation times in terms, primarily of the Zeeman interaction, which is the splitting of degenerate energy levels due to an applied magnetic field. However, in compounds such as Gadolinium(III) complexes with total electron spins higher than 1 (in this case S=7/2) other interactions such as the Zero-Field Splitting(ZFS) play a significant role. ZFS is the splitting of degenerate energy levels in the absence of an external magnetic field. For this purpose, the current research delves into an understanding of the relaxation process, focusing on ZFS in various complexes of interest, using quantum chemical methods as well as molecular dynamic simulations.

The choice of pricing model for software products is a complex procedure due to the different characteristics compared to physical products. This thesis investigates and compares software pricing models in a B2B setting, and describes how KAM plays a role in executing a pricing model. The research has been conducted as an opportunist case study on Adebro, a technology company in the B2B sector. The thesis have come to the following conclusions, with data from interviews and literature: Perpetual license is, and will continue to be, an attractive pricing model for Adebro. However, a subscription-based usage independent pricing model is also attractive for the future. Implications of switching pricing model would be largest when changing between a perpetual and subscription model, where revenue will have the most visual impact. The most important task for KAM is to communicate the change to current and new customers. KAM and the pricing model must also be structured to support each other to be successful. The thesis contributes to science by providing research on pricing models for manufacturing related software. However, studies concerning the weighting of importance for different pricing parameters would be of interest for the future.

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Was geschieht mit der Muttersprache nach der Emigration? Der migrationsbedingte Erwerb einer Zweitsprache kann langfristig zu einem Sprachwechsel bzw. zu einem Verlust der Erstsprache führen. Der Sprachverlust wird zugleich häufig als Identitätsverlust empfunden. Diese Arbeit untersucht die Prozesse, die mit dem Sprachwechsel einhergehen, anhand der sprachlichen Situation der deutschsprachigen Minderheit in Nordgriechenland (Thessaloniki und Umgebung). Die vorliegende Studie stellt die sprachliche Situation, die Sprachwechsel-, Sprachverlust- und Spracherhaltprozesse der Deutschstämmigen aus mikrosoziolinguistischer Perspektive dar. Die sprachlichen Prozesse werden von sprachlichen und außersprachlichen Faktoren, wie zum Beispiel Spracheinstellungen innerhalb der Minderheitengruppe, subjektive Vitalität und ethnische Identitätsprägungen beeinflusst. Sprachliche Identität ist ein zentraler Bestandteil des ethnischen Identitätskonzepts. Sie spielt eine gewichtige Rolle in der Identitätsprägung eines Menschen, einer Minderheit. Die Sprache ist ein Identitätsträger. Die veränderte sprachliche Situation führt zu einem Identitätswechsel oder Identitätsverlust eines Individuums, einer Minderheitengruppe. Anhand der empirischen Untersuchung wird in dieser Arbeit dargestellt, wie die veränderte sprachliche Situation und der Sprachwechsel, der in der ersten, zweiten und dritten Generation der Deutschsprachigen stattfand, zum ethnischen Identitätswechsel dieser Generationen geführt hat. / What happens to the mother tongue after emigrating? The migration-related acquisition of a second language can eventually lead to a language shift or a complete loss of the first language. The loss of language is often also perceived as a loss of identity. This thesis examines the linguistic and non-linguistic processes that are associated with the language shift, based on the linguistic situation of the German-speaking minority in northern Greece (Thessaloniki and surroundings). This study illustrates the linguistic situation of the German diaspora in northern Greece from a micro-sociolinguistic perspective. The linguistic and non-linguistic factors, such as language attitudes of the minority group, individual vitality and ethnic identity affect the above mentioned linguistic processes. Linguistic identity is a central component of the ethnic identity concept. Language plays an important role in the identity of individuals and of ethnic minorities. The language is a carrier of identity. The changing linguistic situation leads to a loss of identity of an individual. Based on the empirical study, the thesis shows how far the language shift, which took place in the first, second and third generation of the Germans, led to an ethnic identity shift of these generations

O objetivo desta pesquisa é avaliar os parâmetros urbanísticos que influenciam a forma urbana e, consequentemente, maximizam a geração de energia fotovoltaica, no município de São Paulo, tomando por estudo de caso o bairro Belenzinho, em processo de adensamento e verticalização. A avaliação dos parâmetros urbanísticos foi realizada por meio do software de modelagem tridimensional Rhinoceros®, utilizando dois vértices: inicialmente, foi modelada a variação isolada dos parâmetros urbanísticos, utilizando Rhinoceros® associado aos plug-ins Grasshopper® e Diva®, com a finalidade de identificar os valores dos parâmetros urbanísticos que maximizam as respostas da forma urbana em relação à incidência de radiação solar na cobertura das edificações; em seguida, adicionou-se o algoritmo genético Galapagos, identificando-se a melhor combinação dos valores dos parâmetros urbanísticos quanto à maximização da incidência de radiação solar na cobertura das edificações. As análises mostraram que no cenário morfológico atual, 86% da cobertura das edificações existentes recebem entre 1840 e 1879 kWh/m2.ano de incidência de radiação solar, porém, algumas edificações são prejudicadas com sombreamento causada pelas edificações vizinhas. Quando se objetiva otimizar a geração de energia solar fotovoltaica na cobertura de empreendimentos distribuídos no tecido urbano, valores de coeficiente de aproveitamento 3, quando o máximo permitido é 4, ou valores de coeficiente de aproveitamento 2, quando o máximo permitido é 2, associados a taxas de ocupação de 0,70, mostram-se apropriados. A aplicação do Galapagos indica que o ganho da radiação solar incidente por área total de cobertura, através da simulação da variação combinada dos parâmetros urbanísticos, é, em média, 60% maior quando comparado com o pior cenário da variação isolada dos parâmetros urbanísticos, no cenário com empreendimentos distribuídos. Porém, quando se objetiva otimizar a geração de energia solar fotovoltaica na cobertura de empreendimentos concentrados no tecido urbano, valores de coeficiente de aproveitamento 3 e 4, quando o máximo permitido é 4, associados a taxas de ocupação de 0,40, mostram-se apropriados. O uso do Galapagos indica que o ganho da radiação solar incidente por área total de cobertura, através da simulação da variação combinada dos parâmetros urbanísticos, é, em média, 40% maior quando comparado com o pior cenário da variação isolada dos parâmetros urbanísticos, no cenário com empreendimentos concentrados. Assim, a pesquisa indica que a definição de uma política energética municipal para aproveitamento fotovoltaico na cobertura de edificações passa pela análise da viabilidade de soluções de geração concentradas ou distribuídas no território urbano, o que impacta em diferentes formas de apropriação dessa variável na regulação da ocupação do solo, no que tange à definição de intervalos de valores dos parâmetros urbanísticos, gabarito de altura, assim como no uso do solo. / The present study analyses the parameters of the urban form that conditions the PV power generation capacity in a neighbourhood in São Paulo: Belenzinho, which is in verticalization and densification processes. The urban analysis was modeled with Rhinoceros® 3D software, with two vertices. Initially, the case-study area was modeled based on the isolated variation of the urban parameters, with Rhinoceros® software associated with Grasshopper® and Diva® plug-ins, in order to identify the best and worse urban parameter values, considering the solar radiation incidence on the rooftops of isolated buildings. Then, Galapagos genetic algorithm was applied for the purpose of combining the urban parameters, and identified the most suitable values for better exploitation of solar radiation. The analysis showed that in the current morphological scenario, 86% of the existing buildings rooftops have values of solar radiation between 1840 and 1879 kWh/m2.year, withal, some buildings are affected by shading caused by neighboring buildings. When optimizing the generation of photovoltaic solar energy in the rooftops of buildings distributed in area of this case study, values 3 for floor area ratio, when the maximum allowed is 4, or values 2 for floor area ratio, when the maximum allowed is 2, associated to values 0.70 of building coverage ratio to be appropriate. The study indicates that the gain of incident solar radiation by total coverage area through the simulation of the Galapagos genetic algorithm, represents on average 60% more when compared to the worst scenario of the isolated variation of the urban parameters, in isolated buildings. However, when the objective is to optimize the generation of photovoltaic solar energy in the rooftops of concentrated buildings in area of case study, values 3 and 4 for floor area ratio, when the maximum allowed is 4, associated to values 0.40 of building coverage ratio to be appropriate. The study indicates that the gain of incident solar radiation by total coverage area through the simulation of the Galapagos genetic algorithm, represents on average 40% more when compared to the worst scenario of the isolated variation of the urban parameters, in concentrated buildings. Thus, the definition of a municipal energy policy for photovoltaic application on the top of buildings involves the analysis of the feasibility of more concentrated or distributed generation solutions in the urban territory, and its appropriation of this variable in the land use regulation, in relation to the definition of ranges of values of urban planning parameters, building\'s height and land use.

The goal of this project was to create a web-based, crowd-sourced, correlational database, that easily allowed users to submit objects and receive correlated objects as results. The webservice was created in the web development languages of HTML, CSS, PHP and Javscript, with MySQL to handle the database. Simultaneous development was kept in check with the aid of the source code management system GIT. Upon completion, the service contained several HTML-views, the ability to add and rate objects, a per-object dedicated page with information parsed from Wikipedia.org, and a view with objects ranked in accordance to the preferences specific to the current user. Roughly a month after the beginning of development, the website was publicly launched and promoted in order to collect data, and improvements were added to the website as needed. Two weeks after the public launch, the collected data was measured and analyzed. The algorithm proved effective and scalable, especially with the introduction of tags and simultaneous computation of object features.

This work is focused on building a content management system for municipal websites. It compares some proprietary and open source systems. Moreover, it aims to create a new content management sys­tem for little-municipal websites. The system is created with a use of PHP script language and MySQL database system. The final application runs on Apache and MySQL servers. This project allows the municipal units to create their own websites easily and quickly. They can define both the structure and the content of the pages. The project is designed to be multi-user. It puts great emphasis on the easiness of use and the blind-friendliness.