T2 relaxation imaging can be used to measure signal from water trapped between myelin bilayers; the ratio of myelin water signal to total water is termed the myelin water fraction (MWF). First, results from multi-component T2 relaxation and diffusion tensor imaging (DTI) were compared for 19 multiple sclerosis (MS) subjects at 1.5 T to better understand how each measure is affected by pathology. In particular, it was determined that the detection of a long-T2 signal within an MS lesion may be indicative of a different underlying pathology than is present in lesions without long-T2 signal. Next, the single-slice T2 relaxation measurement was implemented, refined, and validated at 3.0 T. Scan parameters were varied for phantoms and in-vivo brain, and changes in multi-exponential fit residuals and T2 distribution-derived parameters such as MWF were monitored to determine which scan parameters minimized artifacts. Measurements were compared between 1.5 T and 3.0 T for 10 healthy volunteers. MWF maps were qualitatively similar between field strengths. MWFs were significantly higher at 3.0 T than at 1.5 T, but with a strong correlation between measurements at the different field strengths. Due to long acquisition times, multi-component T2 relaxation has thus far been clinically infeasible. The next study aimed to validate a new 3D multi-component T2 relaxation imaging technique against the 2D single-slice technique most commonly used. Ten healthy volunteers were scanned with both the 2D single-slice and 3D techniques. MWF maps were qualitatively similar between scans. MWF values were highly correlated between the acquisition methods. Although MWF values were generally lower using the 3D technique, they were only significantly so for peripheral brain structures, likely due to increased sensitivity of slab-selective refocusing pulses used for the 3D approach. The 3D T2 relaxation sequence was then applied to the study of MS to take advantage of the increased brain coverage. Thirteen MS subjects and 11 controls underwent T2 relaxation and DTI examinations to produce histograms of MWF and several DTI-derived metrics. MS MWF histograms differed considerably from those of controls, and differences in MS MWF histograms did not mirror differences in DTI histograms relative to matched controls.

Introduction: L'apoptose est un mécanisme étroitement contrôlé qui répond à des besoins particuliers de l'organisme et permet une élimination physiologique des cellules excessives ou endommagées. Elle est donc nécessaire au développement et au maintien du bon fonctionnement de tout organisme vivant puisqu'elle joue un rôle important dans l'embryogenèse, dans les changements morphologiques, dans l'homéostasie cellulaire, dans l'atrophie et la réparation des tissus et dans la régression des tumeurs. Cette forme de mort cellulaire fait intervenir une famille de sérines protéases connues sous le nom de caspases. Leur activation survient après stimulation des cellules par différents facteurs comme des signaux physico-chimiques (UV, rayons gamma), la privation en facteurs de croissance ou une grande variété des molécules chimiques comme les polluants environnementaux et les médicaments anti-cancéreux. Parmi ces derniers on cite l'Adriamycine qui est un médicament anti-tumoral efficace, cependant son utilisation entraîne malheureusement de sévères altérations du fonctionnement cardiaque. Ceci limite par conséquent les doses pouvant être données sans danger aux patients cancéreux. D'autre part l'utilisation clinique de ce médicament semble être également limitée par la résistance que développent certaines formes de tumeurs à la chimiothérapie. Pour surmonter ces deux limites les chercheurs ont essayé de développer certaines stratégies thérapeutiques comme l'hyperthermie, visant à sensibiliser la tumeur aux faibles concentrations des médicaments. Objectifs: La présente étude permettra d'étudier le mécanisme de mort cellulaire induite par l'Adriamycine et l'hyperthermie. Les deux principaux piliers de ce projet sont: (1) Déterminer si l'Adriamycine ou l'hyperthermie utilisées séparément peuvent déclencher l'apoptose chez des cellules tumorales du col utérin humain (HeLa) et chez la même lignée exprimant la protéine de résistance aux médicaments MDR (HeLa MRP). (2) Déterminer si l'hyperthermie pourrait sensibiliser les cellules à l'action de l'Adriamycine. Résultats : L'Adriamycine ou l'hyperthermie utilisés séparément ou combiné avait comme effet une activation de la caspase initiatrice (9) et de la caspase effectrice (3) ainsi qu'un clivage de l'inhibiteur du facteur de fragmentation d'ADN activé par les caspases (ICAD). D'un autre coté l'hyperthermie a causé l'accumulation intracellulaire de l'Adriamycine, la diminution du potentiel membranaire mitochondriale due à une translocation du Bax vers la mitochondrie suivi d'un relarguage du cytochrome c vers le cytosol. Conclusion: L'hyperthermie seule pourrait induire l'apoptose et pourrait servir comme une stratégie utile pour augmenter l'effet pro-apoptotique de l'Adriamycine chez des cellules HeLa parentales ou résistantes aux médicaments (HeLa MRP). ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Hyperthermie, Résistance pléiotropique, MRPl, Apoptose, Adriamycine.

Ce mémoire porte sur la transposition et l'application de la Théorie des Intelligences Multiples (lM) de Howard Gardner, à la classe technique de Ballet. Plus particulièrement, l'étude avait pour buts de concevoir, décrire et illustrer des stratégies visant à stimuler et développer, chacune des intelligences décrites par Gardner (1983), dans la classe technique de ballet. Ce travail découle d'un désir de renouveler la pratique pédagogique de la classe traditionnelle de ballet. La méthodologie a suivi les étapes suivantes: 1) Un examen de la littérature portant sur chaque intelligence selon les angles de leurs identité et caractéristiques: 2) De cet examen a découlé une grille d'analyse appliquée à quatre sources d'informations: a) observation de classes technique de ballet, b) littérature portant sur l'enseignement de la danse et de l'éducation physique, c) mes expériences professionnelles en tant qu'élève, professeur et interprète et d) littérature portant sur les stratégies susceptibles de stimuler les intelligences en contexte académique: 3) L'ensemble de ces informations a été synthétisé dans une discussion théorique du quand et comment chacune des intelligences sont sollicitées en classe technique de ballet: 4) Soixante-cinq stratégies d'enseignement ont été décrites et illustrées, sur la base de la discussion théorique. Ce mémoire conclut qu'en examinant la classe de ballet à travers la lentille de la théorie des lM, un éventail de possibilités d'innovation pédagogique émerge. En diversifiant leurs stratégies pédagogiques, les enseignants peuvent offrir à leurs élèves un enseignement personnalisé. Les élèves sont susceptibles de découvrir et développer leur plein potentiel dans la classe de ballet. Cette façon d'enseigner peut créer un apprentissage approfondi et de longue durée, développer les compétences intellectuelles autant que transversales, tout en créant des liens entre la classe de ballet avec d'autres domaines. Ces retombées sont aussi celles des modèles d'apprentissage constructiviste et de la "critical pedagogical theory", qui mettent l'accent sur des perspectives variées, des activités authentiques et un environnement d'apprentissage reflétant la vie réelle (Fosnot 1996; Ottey, 1996). ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Intelligences multiples, Stratégies d'enseignement, Classe, Technique de ballet.

Multiple metal-gill modelling based on the toxic unit concept suggests that metals with the same toxic actions (e.g. Pb and Cd interacting at Ca-gill channels) will exhibit strictly additive binding at the gills of fish if the concentrations of the two metals sum to one toxic unit. Due to the non-linear nature in which metals bind to fish gills, the metal mixture will be more than additive below one toxic unit and less than additive above one toxic unit. This research tested the models by exposing rainbow trout to mixtures of Cd and Pb to investigate the metal-gill binding of these two metals when present in mixtures with fish. The relationship between Cd and Pb in mixtures was also investigated when natural organic matter (NOM) was added to the treatment solutions. Juvenile rainbow trout (5 g) were exposed to equal mixtures of Cd and Pb at 0.75, 1.5, 2.25 and 3.0 µM each. The high gill-Pb accumulation in relation to gill-Cd was unexpected and suggested an additional gill-binding site for Pb aside from the apical Ca channels on the gill. 96 h toxicity experiments revealed that Cd and Pb in mixtures were more toxic than either Cd or Pb alone. The bioaccumulation and partitioning of Cd and Pb within the body of 50 g rainbow trout was investigated when these fish were exposed to mixtures of Cd and Pb. The accumulation of metals within the trout body did not change between the single metal and mixture exposures. To investigate how Pb affects Cd binding to fish gills, and how these metals exert toxicity when present in mixtures, trout (2 g) were exposed to a range of Cd concentrations (0.75, 1.5, 2.25 and 3.0 µM) while maintaining constant Pb concentrations over the same concentration range. Gill binding results revealed that Pb reduced or inhibited gill-Cd binding. With the addition of NOM, this inhibition was lost. LT50 results for fish exposed to metal mixtures for 96 h revealed that without NOM, the mixture toxicity was dependent on Pb concentration. With the addition of NOM, mixture toxicity decreased with increasing Pb.

In the field of adolescent literacy studies, writing has been neglected in both research and instruction (Juzwik, Curcic, Wolbers, Moxley, Dimling, & Shankland, 2005; Graham & Perin, 2007; Scherff & Piazza, 2005; Troia, 2007), especially in urban settings. Given the importance of writing instruction in secondary education, this qualitative case study investigates the writing experiences of five urban adolescent writers in a high school in a major city in the Southeastern U.S. Research questions included: (1) What are the writing experiences of urban adolescents in and out of school? and (2) In what ways do urban adolescents make use of multiliteracies in their writing experiences? This multicase study (Merriam, 1998; Stake, 1995) includes data collected from interviews, observations, field notes, samples of student work, and electronic messages. For a period of six months, five key participants acted as co-researchers by providing feedback and collaborating on inductive analysis of the data. Findings revealed that students employed multiple modes and genres of writing, and that they viewed social and technological contexts as important factors in their composing experiences. Despite these findings, the students did not have many opportunities to take advantage of recent advancements in 21st century writing approaches. The new ―Age of Composition‖ (Yancey, 2009) has not arrived in urban environments where concerns of power and access remain. This study contributes to the field of literacy studies by illuminating the experiences of the participants and providing recommendations for educators in urban contexts. As Yancey recommends, educators need to design a new model for 21st century composition instruction. The findings of this study suggest the following instructional implications for secondary classrooms: 1. 21st century composition instruction should include multimodal compositions and multimedia projects. 2. 21st century composition instruction should give a central role to the use of technology. 3. Students should have opportunities for personal expression and identity exploration. 4. Teachers should create composition lessons that engage and empower students. 5. 21st century composition instruction should be transformative.

In modern systems for air surveillance, it is important to have a high quality situationassessment. SAAB has a system for air surveillance, and in this thesis possibleimprovements of the tracking performance of this system are explored. The focushas been on improving the tracking of highly maneuverable targets observed withlow sampling rate. To evaluate improvements of the tracking performance, a componentthat is similar to the one used in SAAB’s present tracker was implementedin an Interacting Multiple Model (IMM) structure. The use of an Auxiliary ParticleFilter for improving the tracking performance is explored, and a way to fita particle filter into SAAB’s existing IMM framework is proposed. The differentfilters were implemented in Matlab, and evaluation was done by the meansof Monte Carlo simulations. The results from Monte Carlo simulations show significantimprovement when tracking in two dimensions. However, the results inthree dimensions do not display any substantial overall improvement when usingthe particle filter compared to using SAAB’s present filter. It is therefore notworthwhile to switch the filter used in SAAB’s present tracker for a particle filter,at least not under the high SNR circumstances presented in this thesis. However,further studies within this area are recommended before any final decisions aremade.

In today’s competitive business world, every company wants to be more profitable. In order to keep the profit margin high, the companies need to work more. It is very hard to find any company which works on a single project. Actually it is not only any specific company’s practice rather it is a practice of the entire human being to do multiple works at the same time. The practice has also become quite common in the companies. Although the practice of working on multiple projects simultaneously has become popular for the companies overtime, the important thing is to manage all the projects efficiently so that all projects can be finished according to the plan. Multiple project management deals with a lot of challenges in terms of resource and time. The facts like resource sharing and resource constraint add more complexity to the management of such multiple simultaneous projects. It is difficult to understand the correct workload during the project and the effects of running all the simultaneous projects to the project deployment time. The situation becomes even critical if the projects run in a dynamic environment which may provide changes during any phase of it. Software development is such a process that deals with multiple projects and also the dynamic environment. The master study will focus on such case where the study has conducted in a software development company named ActionWave Development AB. ActionWave Development AB is dealing with multiple projects with having resource constraint. In this study, readers will come to know about the challenges of ActionWave Development AB in terms of resource scenario and deployment time in case of managing multiple projects simultaneously. The study will analyze the effect of having multiple simultaneous projects to the limited resource of ActionWave Development AB and will also show the effects on projects deployment time. The study does the analysis for the current case and an imaginary test case. Later solution has been provided to overcome the problem. Further recommendations were made in order to conduct an effective project management within the company.

Creativity and innovation have become two very important concepts in today’s society where the demand for these abilities are sought after. At the same time, the school system of today follows a more traditional outlook on what learning and knowledge means.The extend students ability to understand and elevate their motivation is possible through creative methods of working. In order to create a school system which can withstand the demands of the future by including creative methods in its model, a study was carried out to examine how teachers’ thoughts on creativity could mean for its development.This study took place in an elementary school in Sweden where Entreprenöriellt Lärande (EL) has been in use for the last two years. Three teachers were interview regarding subjects such as a) creativity and what it means, b) teaching and motivation and c) students abilities. The study showed that the concept of creativity had undergone some changes even though it was thought of as small ones. This in turn affected the work that was being done and the concept of teaching. At the same time, there are constraints in which the teachers are working, for instance limited recourses and having to reach certain goals. The innovative proposal this study contributes is based on those factors the teachers listed as most constraining.

Multiple metal-gill modelling based on the toxic unit concept suggests that metals with the same toxic actions (e.g. Pb and Cd interacting at Ca-gill channels) will exhibit strictly additive binding at the gills of fish if the concentrations of the two metals sum to one toxic unit. Due to the non-linear nature in which metals bind to fish gills, the metal mixture will be more than additive below one toxic unit and less than additive above one toxic unit. This research tested the models by exposing rainbow trout to mixtures of Cd and Pb to investigate the metal-gill binding of these two metals when present in mixtures with fish. The relationship between Cd and Pb in mixtures was also investigated when natural organic matter (NOM) was added to the treatment solutions. Juvenile rainbow trout (5 g) were exposed to equal mixtures of Cd and Pb at 0.75, 1.5, 2.25 and 3.0 µM each. The high gill-Pb accumulation in relation to gill-Cd was unexpected and suggested an additional gill-binding site for Pb aside from the apical Ca channels on the gill. 96 h toxicity experiments revealed that Cd and Pb in mixtures were more toxic than either Cd or Pb alone. The bioaccumulation and partitioning of Cd and Pb within the body of 50 g rainbow trout was investigated when these fish were exposed to mixtures of Cd and Pb. The accumulation of metals within the trout body did not change between the single metal and mixture exposures. To investigate how Pb affects Cd binding to fish gills, and how these metals exert toxicity when present in mixtures, trout (2 g) were exposed to a range of Cd concentrations (0.75, 1.5, 2.25 and 3.0 µM) while maintaining constant Pb concentrations over the same concentration range. Gill binding results revealed that Pb reduced or inhibited gill-Cd binding. With the addition of NOM, this inhibition was lost. LT50 results for fish exposed to metal mixtures for 96 h revealed that without NOM, the mixture toxicity was dependent on Pb concentration. With the addition of NOM, mixture toxicity decreased with increasing Pb.

Sequence alignment has become one of the most common tasks in bioinformatics. Most of the existing sequence alignment methods use general scoring schemes. But these alignments are sometimes not completely relevant because they do not necessarily provide the desired information. It would be extremely difficult, if not impossible, to include any possible objective into an algorithm. Our goal is to allow a working biologist to augment a given alignment with additional information based on their knowledge and objectives.<p></p>In this thesis, we will formally define constraints and compatible constraint sets for an alignment which require some positions of the sequences to be aligned together. Using this approach, one can align some specific segments such as domains within protein sequences by inputting constraints (the positions of the segments on the sequences), and the algorithm will automatically find an optimal alignment in which the segments are aligned together.<p></p>A necessary prerequisite of calculating an alignment is that the constraints inputted be compatible with each other, and we will develop algorithms to check this condition for both pairwise and multiple sequence alignments. The algorithms are based on a depth-first search on a graph that is converted from the constraints and the alignment. We then develop algorithms to perform pairwise and multiple sequence alignments satisfying these compatible constraints.<p></p>Using straightforward dynamic programming for pairwise sequence alignment satisfying a compatible constraint set, an optimal alignment corresponds to a path going through the dynamic programming matrix, and as we are only using single-position constraints, a constraint can be represented as a point on the matrix, so a compatible constraint set is a set of points. We try to determine a new path, rather than the original path, that achieves the highest score which goes through all the compatible constraint set points. The path is a concatenation of sub-paths, so that only the scores in the sub-matrices need to be calculated. This means the time required to get the new path decreases as the number of constraints increases, and it also varies as the positions of the points change. It can be further reduced by using the information from the original alignment, which can offer a significant speed gain.<p></p>We then use exact and progressive algorithms to find multiple sequence alignments satisfying a compatible constraint set, which are extensions of pairwise sequence alignments. With exact algorithms for three sequences, where constraints are represented as lines, we discuss a method to force the optimal path to cross the constraint lines. And with progressive algorithms, we use a set of pairwise alignments satisfying compatible constraints to construct multiple sequence alignments progressively. Because they are more complex, we leave some extensions as future work.