abstract: This thesis presents an overview of the calculation and application of locational marginal prices in electric power systems particularly pertaining to the distribution system. The terminology proposed is a distribution locational marginal price or DLMP. The calculation of locational process in distribution engineering is conjectured and discussed. The use of quadratic programming for this calculation is proposed and illustrated. A small four bus test bed exemplifies the concept and then the concept is expanded to the IEEE 34 bus distribution system. Alternatives for the calculation are presented, and approximations are reviewed. Active power losses in the system are modeled and incorporated by two different methods. These calculation methods are also applied to the 34 bus system. The results from each method are compared to results found using the PowerWorld simulator. The application of energy management using the DLMP to control load is analyzed as well. This analysis entails the use of the DLMP to cause certain controllable loads to decrease when the DLMP is high, and vice-versa. Tests are done to illustrate the impact of energy management using DLMPs for residential, commercial, and industrial controllable loads. Results showing the dynamics of the loads are shown. The use and characteristics of Matlab function FMINCON are presented in an appendix. / Dissertation/Thesis / M.S. Electrical Engineering 2013

Le virus d’Epstein-Barr (EBV) est un herpèsvirus humain qui infecte plus de 90% de la population généralement de façon bénigne et asymptomatique. Cependant, de nombreuses données démontrent que ce virus peut également contribuer à certains processus de cancérisation. En effet, l’EBV est associé à de nombreuses pathologies malignes telles que le lymphome de Burkitt, le lymphome hodgkinien et le carcinome du nasopharynx. Dans la grande majorité de ces cancers associées à ce virus, l’EBV exprime un programme de latence de type II durant lequel la protéine LMP1 est exprimée. Elle est décrite comme l’oncogène majeur de l’EBV car son expression est nécessaire à la survie et à la prolifération des lignées transformées in vitro. Cette protéine membranaire est fonctionnellement apparentée aux membres de la famille des récepteurs du TNF. LMP1 est constitutivement active et son expression conduit à l’activation de voies de signalisation telles que les voies NF-κB, PI3K et des MAPK. L’activation de ces voies de signalisation cellulaire confère à LMP1 des propriétés oncogéniques, cependant, des effets toxiques liés à son expression ont également été décrits. Effectivement, LMP1 est capable d’induire l’apoptose dans différents types cellulaires. Dans ce contexte, nous avons d’abord développé et caractérisé, des variants dérivés de LMP1 constitués de sa partie C-terminale signalisatrice, complète ou partielle, fusionnée à la protéine GFP. Nous montrons que ces variants sont capables de séquestrer les protéines adaptatrices se fixant à LMP1 ou au récepteur TNFR1, et d’inhiber le signal et les phénotypes induits par ces derniers. Ces protéines à effet dominant négatif peuvent ainsi contrecarrer les effets transformants de LMP1 dans des modèles de latence II et III. Ces dominants négatifs peuvent aussi inhiber l’activation du TNFR1 et les phénotypes qui en découlent. Puis, nous avons étudié les propriétés de LMP1 en dehors d’un contexte infectieux et son rôle dans la transformation épithéliale. Nous démontrons que LMP1 induit la mort des cellules épithéliales MDCK mais certaines cellules outrepassent ses effets cytotoxiques générant des lignées qui expriment stablement LMP1 et dans lesquelles cet oncogène viral favorise la survie et exacerbe les phénotypes induits par le facteur de croissance HGF. Le caractère ambivalent de LMP1 pourrait limiter le pouvoir oncogène de l’EBV mais en contrepartie favoriser l’émergence de cellules résistantes à l’apoptose et capables de répondre de façon accrue à des facteurs de croissance. Nos travaux ont permis de mieux comprendre la dualité fonctionnelle de LMP1, d’une part ses effets oncogènes favorisant la survie cellulaire et d’autre part ses propriétés pro-apoptotiques, induites directement ou révélées suite à son inhibition, limitant la tumorigenèse. La caractérisation des mécanismes moléculaires impliquant LMP1 pourrait ainsi participer à la définition de potentielles stratégies thérapeutiques pour le traitement de cancers associés à l’EBV et où LMP1 est exprimée. / Epstein-Barr virus (EBV) is a human herpesvirus that infects more than 90% of worldwide population, generally asymptomatically. However, numerous studies show that EBV promotes tumorigenesis. Indeed, EBV infection is associated with many human malignancies including Burkitt’s lymphoma, Hodgkin’s lymphoma and nasopharyngeal carcinoma. In most of these cancers associated with EBV, it expresses latency II program in which the latent membrane protein 1 (LMP1) is expressed. LMP1 is described as the major EBV oncogene because its expression is necessary in vitro for survival and proliferation of transformed cell lines. This membrane protein is functionally related to members of the TNF receptors superfamily. LMP1 is constitutively active and its expression leads to activation of NF-κB, PI3K and MAPK signaling pathways. These activation confers oncogenic properties to LMP1, however, toxic effects associated with its expression are also described. Indeed, LMP1 can induce cell death in different cell types. In this context, we first developed and characterized LMP1 derivative variants consisting of its C-terminal signal, complete or partial, fused to GFP. We show that these variants are able to sequester adaptors binding to LMP1 and TNFR1, and inhibit signal and phenotypes induced by them. These proteins have dominant negative effect and may counteract LMP1 transformant properties in latency II cellular models. In addition, these dominant negatives impair TNFR1 signaling and associated phenotypes. Then, we studied LMP1 properties outside infectious context and its involvement in epithelial transformation. We show that LMP1 induces cell death in MDCK epithelial cells, but some go beyond its cytotoxic effects generating lines stably expressing LMP1 and in which this viral oncogene promotes survival and exacerbates HGF-induced phenotypes. Ambivalent character of LMP1 could limit the oncogenic potential of EBV but in return support the emergence of cells resistant to apoptosis and able to enhance growth factor responses. Our work allowed us to better understand the functional duality of LMP1 on the one hand its oncogenic effects favoring cell survival and other pro-apoptotic properties, induced directly or reveal by its inhibition, limiting tumorigenesis. Thus, characterization of molecular mechanisms involving LMP1 could participate in the definition of potential therapeutic strategies for treating cancers associated with EBV and where LMP1 is expressed.

As one of the most powerful error-correcting codes, Low-density parity check codes are widely used in digital communications. Because of the performance of LDPC codes are capable to close the shannon limited extraordinarily, LDPC codes are to be used in the new Digital Video Broadcast-Satellite-Second Generation(DVB-S2) and it is the first time that LDPC codes are included in the broadcast standard in 2003. In this thesis, a restructured parity-check matrices which can be divided into sub-matrices for LDPC code in DVB-S2 is provided. Corresponded to this restructured parity-check matrix, a reconstructed decoding table is invented. The encoding table of DVB-S2 standard only could obtain the unknown check nodes from known variable nodes, while the decoding table this thesis provided could obtain the unknown variable nodes from known check nodes what is exactly the Layered-massage passing algorithm needed. Layered-message passing algorithm which also known as "Turbo-decoding message passing" is used to reduce the decoding iterations and memory storage for messages. The thesis also investigate Bp algorithm, lambda-min algorithm, Min-sum algorithm and SISO-s algorithm, meanwhile, simulation results of these algorithms and schedules are also presented.

How to evaluate the performance of an electric power distribution system unambiguously and quantitatively is not easy. How to accurately measure the efficiency of it for a whole year, using real time hour-by-hour Locational Marginal Price data, is difficult. How to utilize distributed computing technology to accomplish these tasks with a timely fashion is challenging. This thesis addresses the issues mentioned above, by investigating feeder performance analysis of electric power distribution systems with distributed algorithm. Feeder performance analysis computes a modeled circuit's performance over an entire year, listing key circuit performance parameters such as efficiency, loading, losses, cost impact, power factor, three phase imbalance, capacity usage and others, providing detailed operating information for the system, and an overview of the performance of every circuit in the system. A diakoptics tearing method and Graph Trace Analysis based distributed computing technology is utilized to speed up the calculation. A general distributed computing architecture is established and a distributed computing algorithm is described. To the best of the author's knowledge, it is the first time that this detailed performance analysis is researched, developed and tested, using a diakoptics based tearing method and Graph Trace Analysis to split the system so that it can be analyzed with distributed computing technology. / Master of Science

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-06-01T12:31:29Z No. of bitstreams: 1 grazielatoledocostamayrink.pdf: 5985830 bytes, checksum: 06ca10d53dd3ecb4c31ad3500ea80e8c (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-06-02T15:13:59Z (GMT) No. of bitstreams: 1 grazielatoledocostamayrink.pdf: 5985830 bytes, checksum: 06ca10d53dd3ecb4c31ad3500ea80e8c (MD5) / Made available in DSpace on 2017-06-02T15:13:59Z (GMT). No. of bitstreams: 1 grazielatoledocostamayrink.pdf: 5985830 bytes, checksum: 06ca10d53dd3ecb4c31ad3500ea80e8c (MD5) Previous issue date: 2016-08-10 / Introdução: A associação entre Linfoma de Hodgkin clássico e o status tumoral do vírus Epstein- Barr é bem definida. Entretanto, a expressão da positividade do vírus Epstein-Barr nas células de Reed-Sternberg/Hodgkin e o impacto dessa relação na sobrevida do Linfoma de Hodgkin clássico permanecem controversos e apresentam resultados conflitantes em estudos de diversas regiões do mundo. Considera-se essencial o entendimento fisiopatogênico desse vírus no prognóstico dos pacientes com Linfoma de Hodgkin clássico. Objetivo: Correlacionar o status do vírus Epstein Barr com os fatores de risco desfavoráveis e fatores prognósticos do Linfoma de Hodgkin clássico em uma população brasileira. Métodos: A positividade do vírus Epstein-Barr foi determinada pelo método de Hibridização in situ para o ácido ribonucleico viral e pela imuno-histoquímica para proteína de membrana latente viral 1. A revisão histopatológica das amostras e a análise dos testes de identificação foram realizadas por uma hematopatologista experiente. Avaliou-se o impacto prognóstico do status do vírus Epstein-Barr em 29 pacientes com Linfoma de Hodgkin clássico. Os fatores prognósticos do Escore Prognóstico Internacional para estadio avançado e os fatores de risco desfavoráveis instituídos pelo Grupo Alemão de Estudos em Hodgkin para estadio limitado foram correlacionados com o status viral nas células tumorais. Para as associações entre presença do vírus Epstein-Barr e outras variáveis categóricas, aplicaram-se os testes de Qui-quadrado ou exato de Fisher. A Sobrevida Global e a Sobrevida Livre de Eventos foram analisadas pelo método de Kaplain-Meier e Modelo de Regressão Proporcional de Cox. Resultados: A média de idade ao diagnóstico foi 33 anos. O status do vírus Epstein-Barr nas células tumorais foi positivo em 37,9%. As células tumorais positivas para o vírus foram mais frequentes em pacientes com idade maior que 45 anos, sem diferença estatística. O subtipo celularidade mista foi o mais frequente (p = 0,02) e o tamanho de efeito desse teste foi de moderada magnitude. Na análise univariada, as sobrevidas Livre de Eventos e Global não apresentaram significância estatística para idade, sexo, estadio clínico, hemoglobina, leucocitose, linfocitopenia, albumina, envolvimento nodal, sintomas B, doença extranodal e doença Bulky entre os pacientes positivos e negativos para o vírus Epstein-Barr (p > 0,05). Os pacientes positivos apresentaram maior Sobrevida Livre de Eventos quando comparados aos pacientes negativos, embora a diferença não apresentasse significância (p = 0,07). Na análise multivariada, a positividade ao vírus Epstein-Barr não demonstrou fator prognóstico significante. Conclusões: Apesar do status do vírus Epstein-Barr nas células tumorais não ter revelado associação com fatores prognósticos adversos e não ter influenciado a Sobrevida Global e a Sobrevida Livre de Eventos, observou-se uma associação positiva entre a presença desse vírus e o subtipo celularidade mista, demonstrando uma relação com o subtipo histológico de pior prognóstico. / Introduction: The association between classical Hodgkin’s Lymphoma and tumor Epstein-Barr virus status is well established. However, the expression of Epstein-Barr virus presence in Hodgkin/Reed-Sternberg cells and its prognosis remains controversial and presentes conflicting results in studies worldwide. Understanding the pathophysiological role of this virus in the prognosis of patients with classical Hodgkin’s Lymphoma is essential. Objective: The aim of this study is to correlate the clinical outcome with Epstein-Barr virus status in a Brazilian population. Methods: Epstein-Barr virus positivity was determined by in situ hybridization for Epstein-Barr virus-encoded ribonucleic acid and immunohistochemistry for viral latent membrane protein-1. The histopathology review and the analysis of identification tests were performed by an hematopathologist expert. The prognostic impact of Epstein-Barr virus status in 29 patients with classical Hodgkin’s Lymphoma was evaluated. Prognostic factors from International Prognostic Score to advanced stage and risk factors from German Hodgkin Study Group to limited stage were correlated with tumor cells Epstein-Barr virus status. In order to determine associations between the presence of Epstein-Barr virus and other categorical variables, Chi-square or Fisher's exact tests were applied. Overall and event-free survivals were analyzed with Kaplan-Meier method and Cox proportional hazards regression models. Results: The mean age at diagnosis was 33 years. Tumor cells Epstein-Barr virus status was positive in 37.9%. Epstein-Barr virus-positive classical Hodgkin’s Lymphoma was more frequent in patients older than 45 years, with no statistical difference. Mixed cellularity histological subtype was more common in Epstein-Barr virus-related tumor cells (p = 0.02) and its effect-size index was medium. Univariate analysis, event-free survival and overall survival were not significantly associated to age, sex, clinical stage, hemoglobin, leukocytes, lymphocytes, albumin, nodal involvement, B symptoms, extranodal disease and Bulky disease in Epstein-Barr virus-positive and negative patients (p > 0.05). Epstein-Barr virus-positive patients had longer event free survival when compared to Epstein-Barr virus-negative ones, even though the difference was not statistically significant (p = 0.07). In multivariate analysis, Epstein Barr virus positivity was not a significant prognostic factor. Conclusions: Although the Epstein-Barr virus status in tumor cells was not associated with adverse prognostic factors and did not influence the overall and event-free survivals, a positive association between the presence of Epstein-Barr virus and Mixed-cellularity subtype was noticed.

Le virus d'Epstein-Barr (EBV) est un herpèsvirus humain qui infecte plus de 90% de la population généralement de façon bénigne et asymptomatique. Cependant, de nombreuses données démontrent que ce virus peut également contribuer à certains processus de cancérisation. En effet, l'EBV est associé à de nombreuses pathologies malignes telles que le lymphome de Burkitt, le lymphome hodgkinien et le carcinome du nasopharynx. Dans la grande majorité de ces cancers associées à ce virus, l'EBV exprime un programme de latence de type II durant lequel la protéine LMP1 est exprimée. Elle est décrite comme l'oncogène majeur de l'EBV car son expression est nécessaire à la survie et à la prolifération des lignées transformées in vitro. Cette protéine membranaire est fonctionnellement apparentée aux membres de la famille des récepteurs du TNF. LMP1 est constitutivement active et son expression conduit à l'activation de voies de signalisation telles que les voies NF-κB, PI3K et des MAPK. L'activation de ces voies de signalisation cellulaire confère à LMP1 des propriétés oncogéniques, cependant, des effets toxiques liés à son expression ont également été décrits. Effectivement, LMP1 est capable d'induire l'apoptose dans différents types cellulaires. Dans ce contexte, nous avons d'abord développé et caractérisé, des variants dérivés de LMP1 constitués de sa partie C-terminale signalisatrice, complète ou partielle, fusionnée à la protéine GFP. Nous montrons que ces variants sont capables de séquestrer les protéines adaptatrices se fixant à LMP1 ou au récepteur TNFR1, et d'inhiber le signal et les phénotypes induits par ces derniers. Ces protéines à effet dominant négatif peuvent ainsi contrecarrer les effets transformants de LMP1 dans des modèles de latence II et III. Ces dominants négatifs peuvent aussi inhiber l'activation du TNFR1 et les phénotypes qui en découlent. Puis, nous avons étudié les propriétés de LMP1 en dehors d'un contexte infectieux et son rôle dans la transformation épithéliale. Nous démontrons que LMP1 induit la mort des cellules épithéliales MDCK mais certaines cellules outrepassent ses effets cytotoxiques générant des lignées qui expriment stablement LMP1 et dans lesquelles cet oncogène viral favorise la survie et exacerbe les phénotypes induits par le facteur de croissance HGF. Le caractère ambivalent de LMP1 pourrait limiter le pouvoir oncogène de l'EBV mais en contrepartie favoriser l'émergence de cellules résistantes à l'apoptose et capables de répondre de façon accrue à des facteurs de croissance. Nos travaux ont permis de mieux comprendre la dualité fonctionnelle de LMP1, d'une part ses effets oncogènes favorisant la survie cellulaire et d'autre part ses propriétés pro-apoptotiques, induites directement ou révélées suite à son inhibition, limitant la tumorigenèse. La caractérisation des mécanismes moléculaires impliquant LMP1 pourrait ainsi participer à la définition de potentielles stratégies thérapeutiques pour le traitement de cancers associés à l'EBV et où LMP1 est exprimée.

L'avènement de l'IDM (Ingénierie Dirigée par les Modèles) a suscité beaucoup d'intérêt de la part des organisations qui de fait commencent à transformer leur processus de développement traditionnel en un processus de développement dirigé par les modèles, appelé aussi processus IDM.Au moment où ces processus commencent à émerger, nous notons l'absence d'un langage dédié pour les modéliser et les mettre en œuvre. Le standard SPEM 2.0 propose des concepts génériques qui sont supposés être capables de décrire tout type de processus logiciel. Cependant, les concepts de SPEM ne capturent pas la nature exacte des processus IDM. D'autre part, une autre insuffisance majeure de SPEM réside dans le fait qu'il n'intègre pas les concepts relatifs à la mise en œuvre des processus.L'objectif de cette thèse est triple : (1) proposer une extension de SPEM dans laquelle les concepts centraux des processus IDM sont réifiés ; (2) proposer un langage dédié à la modélisation comportementale des processus IDM ; (3) proposer une architecture conceptuelle d'un environnement logiciel d'aide à la modélisation et à la mise en œuvre des processus IDM.Pour valider notre approche, un prototype a été développé sous l'environnement TOPCASED. Ce prototype fournit d'une part un éditeur graphique pour la modélisation structurelle et comportementale des processus IDM et d'autre part un environnement de mise en œuvre s'appuyant sur les modèles comportementaux des processus. Nous avons également appliqué notre approche à une étude de cas significatif: le processus UWE (UML-based Web Engineering), qui est un processus IDM dédié au développement d'applications web.

In this thesis, methods of charging for the transmission system and optimising the expansion of the transmission network under the competitive power market are described. The first part of this thesis considers transmission tariff design. In the proposed approach, not only is all the necessary investment in the transmission system recovered, but also an absolute economic signal is offered which is very useful in the competitive power market. A fair power market opportunity is given to every participant by the new nodal-use method. The second part of this thesis considers transmission system expansion. All the tests are based on the Three Gorges Project in China. In this thesis, to optimally expand the transmission system, the LMP (Locational Marginal Price) selection method and the CBEP (Congestion-Based transmission system Expansion Planning) method are introduced. The LMP selection method is used to select optional plans for transmission system expansion. It is especially suitable for large transmission systems. The outstanding advantages of the LMP selection method are simplicity and computational efficiency. The CBEP method produces the optimal system expansion plan. For the first time, generation congestion and transmission congestion are separated within the system expansion problem. For this reason the CBEP method can be used in a supply-side power market and is suitable for the Chinese power market. In this thesis, the issue of how to relax the congestion in the transmission system have been solved. The transmission system can obtain enough income to recover the total required cost. For this reason more and more investment will come into the transmission system from investors. The risk for the independent generators is also under control in the CBEP method. Even when the system is congested, the uncertainty of LMP is taken into consideration.

<p>B-cell chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Although treatment of this disease has advanced considerably over the past decade, CLL remains incurable with current chemotherapeutics. In addition, available drug regimens for CLL are associated with frequent cytopenia-related complications, such as infection and fatigue. Thus, the major challenge in CLL treatment today is the need for alternative therapeutics with decreased toxicity and improved efficacy for disease refractory to currently available drugs.</p><p> </p><p>CLL is characterized by slow accumulation of malignant cells, which are supported in the microenvironment by cell-cell interactions and soluble cytokines such as tumor necrosis factor (TNF). We evaluated the effect of the small molecule TNF inhibitor LMP-420 on primary CLL cells. LMP-420 exhibited cytotoxic activity against these cells in the MTS assay, with similar potency to the front-line CLL drug fludarabine. LMP-420 induced time- and dose-dependent apoptosis in CLL cells, as demonstrated by annexin V staining, caspase activation, and DNA fragmentation. These changes were associated with decreased expression of the anti-apoptotic proteins Mcl-1, Bcl-xL, Bcl-2, and XIAP. CLL cells from patients with poor prognostic indicators exhibited LMP-420 sensitivity equal to that for cells from patients with favorable characteristics. In addition, LMP-420 potentiated the cytotoxic effect of fludarabine and inhibited in vitro proliferation of CLL cells. In contrast to other CLL therapeutics, LMP-420 exhibited minimal effects on normal peripheral blood mononuclear cell viability, mitogen-stimulated B- and T-cell proliferation, and hematopoietic colony formation. Our data suggest that LMP-420 may be a useful treatment for CLL with negligible hematologic toxicities. </p><p> </p><p>The effect profile of this compound in normal immune cells and the microarray studies in CLL cells indicate that the mechanism of action of LMP-420 likely involves modulation of the NF-kB pathway. Our initial studies demonstrate moderate but significant inhibitory activity against p65, a key member of the NF-kB transcription factor family. Research is ongoing to gain a better understanding of the specific cytotoxicity of LMP-420 for CLL cells and to elucidate other components of its mechanism of action. Regardless of the ultimate mechanistic findings with LMP-420, our studies support this molecule as a promising new CLL therapeutic that warrants further preclinical evaluation.</p> / Dissertation

L’avènement de l’IDM (Ingénierie Dirigée par les Modèles) a suscité beaucoup d’intérêt de la part des organisations qui de fait commencent à transformer leur processus de développement traditionnel en un processus de développement dirigé par les modèles, appelé aussi processus IDM.Au moment où ces processus commencent à émerger, nous notons l’absence d’un langage dédié pour les modéliser et les mettre en œuvre. Le standard SPEM 2.0 propose des concepts génériques qui sont supposés être capables de décrire tout type de processus logiciel. Cependant, les concepts de SPEM ne capturent pas la nature exacte des processus IDM. D’autre part, une autre insuffisance majeure de SPEM réside dans le fait qu’il n’intègre pas les concepts relatifs à la mise en œuvre des processus.L’objectif de cette thèse est triple : (1) proposer une extension de SPEM dans laquelle les concepts centraux des processus IDM sont réifiés ; (2) proposer un langage dédié à la modélisation comportementale des processus IDM ; (3) proposer une architecture conceptuelle d’un environnement logiciel d’aide à la modélisation et à la mise en œuvre des processus IDM.Pour valider notre approche, un prototype a été développé sous l’environnement TOPCASED. Ce prototype fournit d’une part un éditeur graphique pour la modélisation structurelle et comportementale des processus IDM et d’autre part un environnement de mise en œuvre s’appuyant sur les modèles comportementaux des processus. Nous avons également appliqué notre approche à une étude de cas significatif: le processus UWE (UML-based Web Engineering), qui est un processus IDM dédié au développement d’applications web. / With the emergence of MDE, many organizations have been starting to transform their traditional software development processes into model-driven processes. Kleppe and al. define a model-driven software development as “a process of developing software using different models on different levels of abstraction with (automated) transformations between these models”.While model-driven development processes – called MDE processes – have started to appear, a tool-supported Process Modeling Language (PML) for describing and enacting such processes is still lacking. The concepts of SPEM 2.0 are quite generic since they are supposed to allow describing any kind of software. However, SPEM 2.0 concepts do not succeed in capturing the exact nature of most activities and artifacts of model-driven development. In addition, another major weakness of SPEM 2.0 is the lack of concepts for process enactment.The objective of this thesis is threefold: (1) provide an extension of SPEM that reifies the MDE concepts; (2) provide a language dedicated to behavioral modeling of MDE processes; (3) provide a conceptual architecture of a PSEE (Process-centered Software Engineering Environment) that guides process designer at modeling phase and developers at enactment time.To validate our approach, a prototype of this PSEE is developed under the TOPCASED environment. This prototype provides a graphical editor for structural and behavioral modeling of MDE processes, and a process enactment engine based on process behavior models. We have also applied our approach to a significant case study: the UWE (UML-based Web Engineering) process, which is a MDE process dedicated to web applications development.