Notre travail de recherche s’inscrit dans le cadre du projet de recherche REDiM (Réingénierie des EIAH Dirigée par les Modèles) qui porte sur la réingénierie d'un scénario pédagogique. Il se focalise plus précisément sur l'analyse de traces collectées en session par un EIAH pour fournir à l'enseignant des indicateurs calculés.Dans notre contexte de travail, UTL (Usage Tracking Language) permet de définir des indicateurs sous une forme proche des patrons de conception. Il a été conçu pour répondre aux questions de capitalisation et de réutilisation. Par contre, UTL ne disposait initialement pas de moyens pour spécifier formellement la façon de calculer l’indicateur à partir des traces collectées. De plus, les approches par développement ad hoc d’indicateurs ne permettent pas de modéliser de façon formelle la méthode de calcul. En général, les patrons de conception se limitent à la description, ils ne peuvent donc pas être automatisés. Des descriptions textuelles dans UTL pour produire un indicateur à partir des traces ne permettent pas de générer automatiquement les valeurs d’un indicateur.Notre principal objectif de recherche a donc été de définir des modèles, des méthodes et des outils pour la formalisation et l’automatisation du calcul d’indicateurs. Pour cela, nous avons élaboré une nouvelle version d’UTL qui intègre un langage de combinaison de données nommé DCL4UTL, qui permet de modéliser des indicateurs sous une forme capitalisable, automatisable et réutilisable afin de fournir des indicateurs signifiants à l’enseignant/concepteur. Ces indicateurs peuvent être calculés en temps réel ou après une session, respectivement dans un contexte de tutorat ou de réingénierie du scénario pédagogique.L'originalité de notre approche réside dans le fait que cette version permet non seulement de capitaliser des savoir-faire sur les techniques d'analyse d'usage d'un EIAH, mais aussi, avec le langage DCL4UTL (1) de décrire formellement dans une forme générique des méthodes de modélisation et de calcul d’indicateurs à partir des traces collectées par un EIAH, (2) d’intégrer des fonctions externes (qui proviennent d’autres outils d’analyse), et (3) de créer des données intermédiaires paramétrées facilitant la modélisation et la réutilisation de la méthode de calcul d’indicateurs. Nous avons également développé un outil d’analyse pour calculer les indicateurs modélisés.Cette version est le résultat d'une étude théorique et d’une analyse de l’état de l’art, mais aussi de travaux exploratoires sur la modélisation d’indicateurs et l’analyse de traces. L’approche et le langage ont été validés par plusieurs expérimentations avec plusieurs EIAH existants. / The research topic of this thesis is a part of the REDIM (model driven re-engineering) research project. It focuses specifically on the analysis of tracks collected during the learning session by a TEL (Technology Enhanced Learning) system in order to provide teachers indicators calculated. In our work environment, UTL (Usage Tracking Language) allows users to define the indicators in a form close to the design patterns. It was designed to response capitalization and reuse questions. However, UTL did not initially have any means to formally specify how to calculate indicators based on tracks collected. In general, design patterns are limited to the description, they cannot be automated. In addition, textual descriptions in UTL to produce indicators from tracks do not allow generating automatically an indicator’s values.Our main research objective was therefore to define models, methods and tools for formalizing and automating the calculation of indicators. We propose an extension for UTL named DCL4UTL (Data Combination Language for UTL) to model indicators in a capitalizable, automatable and reusable form to provide meaningful indicators to teachers/designers. With this new version, the indicators can be calculated in real-time or after a learning session in the context of tutoring actions or the reengineering of learning scenarios, respectively.The originality of our approach (DCL4UTL) lies in the fact that this version not only capitalize know-how on analysis techniques of the use an TEL system, but also (1) formally describe models and calculation methods of indicators from tracks collected by a TEL system, (2) integrate external functions (from other analysis tools), and (3) create parameterized intermediate data facilitating the modeling and reuse of indicators’ calculation method. We have also developed an analysis tool to calculate modeled indicators. Our approach and language have been validated by several experiments with several existent TEL systems.

Le rhabdomyosarcome de l'adulte est une tumeur rare au pronostic. Le présent travail propose d'étudier les caractéristiques cliniques et moléculaires et la prise en charge des adolescents et adultes atteints de rhabdomyosarcome ainsi que la possibilité de combinaison de thérapie ciblées sur lignées cellulaires in vitro. Nous avons anamysé rétrospectivement 239 patients âgés de 10 ans ou plus, atteints de rhabdomyosarcome au MD Anderson Cancer Center entre 1957 et 2003 et leur statut fusionnel pour PAX-FOXO1 par hybridation in situ en fluorescence. Trois lignées cellulaire de sarcome à petites cellules ont été soumises à des combinaisons de thérapies ciblées avec analyse de la viabilité. Les patients de plus de 50 ans avaient une survie globale à 5 ans de 13 % (médiane de survi à 1.7 ans) en dépit d'une maladie localisée. Approximativement 13 % des patients métastasiques de moins de 50 ans ont eu une survie prolongée de plus de 15 ans. L'utilisation d'une stratégie thérapeutique triple, intégrant chirurgie, chimiothérapie et radiothérapie était signifcativement associée à une survie prolongée. Auniveau molécualire, la présence du transcrit de fusio PAX3/7-FOXO1 était significativement liée à un risque accru de maladie métastatique. L'étude in vitro de thérapies ciblées a permis d'identifier la combinaison du vorinostat plus le 17DMAG associée à la doxorubicine comme ayant une meilleure efficacité. La prise en charge du rhabdomyosarcome de l'adolescent et de l'adulte semble souffrir d'une approche moins agressive comparée au rhabdomyosarcome pédiatrique. De plus, des combianaisons de thérapies ciblées peuvent être intégrées aux protocoles de chimiothérapies standards. / Rhabdomyosarcoma is a rare entity adult patient with unfavourable outcome. This work describes the clinical and molecular specificities of adolescent and adult type of rhabdomyosarcoma and investigates the optimal integration of targetd therapy combinations on small cell sarcoma cell lines in vitro. We retrospectively analyzed 239 patients, 10 years of age and greater, diagonsed withrhabdomyosarcoma at MD Anderson Cancer Center from 1957 trough 2003 and their PAX-FOXO1 fusion gene status by fluorescence in situ hybridization on tissues microarray. Three samll cell sarcoma cell lines were exposed to targetd agent combinations. PAtient with metastatic rhabdomyosarcoma were found to have a 18 % survival rate at 5 years from diagnosis with an 12 %survival past 15 years. This outcome was even poorer for patients over 50 of age, even with localized disease. Younger patients were more likely to receive multidisciplinary therapy than their older counterparts. The presence of PAX-FOXO1 tranlocation was significantly associated with a higher frequency of metastatic disease. The four agents with the exception of abacavir synergized two by two with each other in vitro but the triple combinations did not perform beter than the bitherapies. The dual therapies vorinostat 5HDAC inhibitor) plus 17-DMAG (Hsp90 inhibitor) added with doxorubicin achvied better results than dual or triple therapies. Adult patient with rhabdomyosarcoma present similar molecular and clinical characteristics compared pediatric patients but outcome decrease with age partly du to a less multimodal management. Moreover targeted combinations should be integrated to chemotherapy backbone.

The aim of this work is to identify the possibilities of the complementary usage of two analytical methods of data analysis, OLAP analysis and data mining represented by GUHA association rule mining. The usage of these two methods in the context of proposed scenarios on one dataset presumes a synergistic effect, surpassing the knowledge acquired by these two methods independently. This is the main contribution of the work. Another contribution is the original use of GUHA association rules where the mining is performed on aggregated data. In their abilities, GUHA association rules outperform classic association rules referred to the literature. The experiments on real data demonstrate the finding of unusual trends in data that would be very difficult to acquire using standard methods of OLAP analysis, the time consuming manual browsing of an OLAP cube. On the other hand, the actual use of association rules loses a general overview of data. It is possible to declare that these two methods complement each other very well. The part of the solution is also usage of LMCL scripting language that automates selected parts of the data mining process. The proposed recommender system would shield the user from association rules, thereby enabling common analysts ignorant of the association rules to use their possibilities. The thesis combines quantitative and qualitative research. Quantitative research is represented by experiments on a real dataset, proposal of a recommender system and implementation of the selected parts of the association rules mining process by LISp-Miner Control Language. Qualitative research is represented by structured interviews with selected experts from the fields of data mining and business intelligence who confirm the meaningfulness of the proposed methods.

Integrating decision analytical techniques in geographic information systems (GIS) can help remove the two primary obstacles in spatial decision making: inaccessibility to required geographic data and difficulties in synthesizing various criteria. I developed a GIS model to assist people seeking optimal residential locations. Fuzzy set theory was used to codify criteria for each factor used in evaluating residential locations, and weighted linear combination (WLC) was employed to simulate users' preferences in decision making. Three examples were used to demonstrate the applications in the study area. The results from the examples were analyzed. The model and the ArcGIS Extension can be used in other geographic areas for residential location selection, or in other applications of spatial decision making.

Une méthodologie générale et efficace pour la synthèse de nanoparticules de prodrogues polymères hétérotéléchéliques à hauts taux de charge a été mise au point en combinant d’une part la méthode dite du “principe actif amorceur” pour obtenir des prodrogues polymères α-fonctionnelles par polymérisation radicalaire contrôlée par les nitroxydes (NMP), et d’autre part la réaction d'échange de nitroxyde à partir d’un nitroxyde fonctionnel pour coupler une seconde molécule d'intérêt en bout de chaîne. Une petite bibliothèque de prodrogues polymères hétérotéléchéliques avec différentes combinaisons pour diverses applications (e.g., libération de principes actifs, imagerie/théranostic, thérapie combinée, ciblage actif) a été synthétisée en utilisant le polyisoprène (PI) comme polymère.En particulier, une alcoxyamine basée sur le nitroxyde SG1 a été fonctionnalisée avec la première molécule d’intérêt et utilisée pour polymériser l'isoprène par NMP et donner la prodrogue polymère désirée. En appliquant ensuite la réaction d'échange de nitroxyde à partir du nitroxyde TEMPO fonctionnalisé avec la seconde molécule d’intérêt, le nitroxyde SG1 en bout de chaîne a été quantitativement remplacé par le TEMPO fonctionnel pour donner la prodrogues hétérobifonctionnelle. Cette approche générale a été appliquée aux combinaisons suivantes : (i) gemcitabine (Gem)/rhodamine (Rho) et Gem/cyanine pour la libération de principes actifs et l’imagerie; (ii) aminoglutethimide (Agm)/doxorubicine (Dox), Gem/Dox and Gem/Lapatinib (Lap) pour la thérapie combinée et (iii) Gem/biotine pour la libération de principes actifs et le ciblage actif in vitro et in vivo. Les propriétés d’imagerie des nanoparticules de prodrogues polymères comportant une molecule fluorescente ont été étudiées in vitro et in vivo, respectivement en termes d’internalisation intracellulaire et de biodistribution. Pour les thérapies combinées, la cytotoxicité in vitro des différentes nanoparticules a été étudiée et comparée à celle émanant d’autres strategies de délivrance de deux principes actifs (e.g., conanoprécipitation, mélange physique de nanoparticules).Enfin, des prodrogues polymères hétérobifonctionnelles comprenant l’adénosine en début de chaîne et un motif maléimide en fin de chaine ont été préparées et fonctionnalisées en surface par des protéines capables de promouvoir le passage des nanoparticules à travers la barrière hémato-encéphalique pour libérer l’adénosine au niveau du cerveau. / A facile and versatile synthetic platform to prepare high drug loading, heterobifunctional polymer prodrug nanoparticles was developed by combining the “drug-initiated” method to obtain α-functional polymer prodrugs by nitroxide-mediated polymerization (NMP), and the nitroxide exchange reaction from a functional nitroxide to attach a second molecule of interest at the ω chain-end. A library of heterotelechelic polymers prodrugs with different combinations for various purposes (e.g., drug delivery, imaging/theranostic, combination therapy, active targeting) was prepared using polyisoprene (PI) as polymer scaffold. More specifically, an alkoxyamine based on the SG1 nitroxide was functionalized with the first drug of interest and used to perform the NMP of isoprene to yield the desired polymer prodrug. Subsequently, by applying the nitroxide exchange reaction using a TEMPO nitroxide functionalized with the second molecule of interest, the SG1 nitroxide at the chain-end was quantitatively replaced by the functional TEMPO and the desired heterobifunctional polymer prodrug was formed. This general methodology was applied to the following combinations: (i) gemcitabine (Gem)/rhodamine (Rho) and Gem/cyanine for drug delivery and imaging; (ii) aminoglutethimide (Agm)/doxorubicin (Dox), Gem/Dox and Gem/Lapatinib (Lap) for combination therapy and (iii) Gem/biotin for drug delivery and active targeting in vitro and in vivo. For polymer prodrug nanoparticles bearing fluorescent dyes, in vitro and in vivo imaging studies were performed to investigate their cellular internalization and their biodistribution, respectively. As for the different combination therapies, the in vitro cytotoxicity of the nanoparticles was determined and compared to that of other strategies to deliver two different drugs (e.g., conanoprecipitation, physical mixture of nanoparticles).Finally, heterobifunctional polymer prodrugs bearing adenosine in alfa position and a maleimide moiety in omega position were synthesized to give nanoparticles that were further surface-functionalized with different proteins able to promote crossing through the blood brain barrier for drug delivery to the brain.

In the world there are adverse climates, climates that hinder the good construction and paving of roads, generating insecurity among the locals and visitors. This over time affects the economy of a country, as a road boosts tourism, transport and commerce. Therefore, a mixture was designed to mitigate a problem in the placement of hot asphalt mixture at temperatures below zero degrees Celsius. That is, a conventional mix design was proposed, but with different types of filler (lime, Portland cement type I and silica) tested with the Marshall and Lottman method which are governed according to the EG-2013 standards [1] and parameters established in the Asphalt Institute [2]. To find the optimum, it was tested with 5.0%, 5.5% 6.0% and 6.5% asphalt cement. Then with the results obtained a comparative analysis was performed. Finally, specimens without any additives were made, the specimens once prepared at 140°C were subjected to freezing, resulting in the three types of filler, that the hot asphalt mixture with incorporation of Portland cement type I to a 5, 90% of asphalt cement is the optimum since, subject to extreme temperatures below 0°C they comply with the parameters required in the standards.

This diploma thesis deals with the assessment of the influence of the location in the historic zone on the price of a commercially usable building. The thesis includes the elaboration of the current legal regulations influencing the property valuation, the definition of basic concepts related to the valuation of a selected real estate, and the determination of methods usable in the process of commercial object valuation. Furthermore, the cities of Třebíč, in which the valued property is located, and Žďár nad Sázavou, that is used for comparison, are described in detail. The selected method is a combination of the cost and income approach for valuation according to the price regulation, and in the case of market valuation of seloected real estate, the method of direct comparison is used. Finally, the influences that may have an impact on the object value are assessed.

The topic of this Master’s thesis is combination of laser spectroscopic methods. LIBS and Raman spectroscopy were chosen for the combination. This combination is applied to plastic identification and separation as a mean to automate sorting of plastic waste. Data handling was done via different methods of computer learning algorithms scripted in R language. Plastic sorting accuracy over 90 % was reached thanks to the combination of chosen methods. This work also addresses some issues implied by combination of two different methods.

The aim of this work is to study and describe the principles and method of delineation of ECG signals. Learn and describe about method of cluster analysis. In this work was created and described three different methods of delineations of ECG signals. Created algorithms were tested on complete CSE database. With cluster analysis were combine created methods. The obtained results from realized methods and combined method were compared with others known methods. At the end of this work is evaluate efficiency of detection of combined method.

Subject of the thesis is the architecture study of multifunctional architectural object based on the principle of creating intensive urban structures. Design area is located on the riverside Svitava, in the neighborhood the street Zvonařka . The aim of the project was to design an intensive structure that will meet the combination of features in order to achieve independence from the surrounding area and shorten the walking distance. The proposal itself, the principle of porosity. This generates a set of objects fulfilling different functions, public, semi-public and private spaces - atrium terraces, green roofs and balconies. The building has nine floors above ground and two underground floors used for parking. On the first floor there is a bank and retail space, the other floors are then situated administration, library, fitness, health center and on the top two floors of living. Construction of the building is designed as a reinforced concrete frame, sits on the pilots. The facade is solved soberly with regard to function, the main expressive elements are white façade,gray facing and glazing surface of the first two floors