Made available in DSpace on 2016-06-02T19:06:20Z (GMT). No. of bitstreams: 1 6500.pdf: 5345644 bytes, checksum: e886844b4ba61e58d704a8babf113721 (MD5) Previous issue date: 2014-10-21 / Maintaining legacy systems is a complex and expensive activity for many companies. A recently proposal to solve this problem is Architecture-Driven Modernization (ADM), proposed by Object Management Group (OMG). The ADM consists of a set of concepts and standard metamodels that support systems modernization using models. The Knowledge Discovery Metamodel (KDM) is the main metamodel of ADM, it can represent many artifacts of a legacy system, such as source code, architecture, user interface, configuration files and business process. In general, legacy systems have crosscutting concerns, it can show source code problems like tangling and scattering, and it raises the maintenance costs. The aspect orientation is an alternative to improve crosscutting concerns modularization. Thus, in this dissertation is presented the term Aspect Oriented Modernization that uses the aspect oriented concepts in the ADM context. This modernization process consists in modularize legacy systems with aspects represented in model level. To achieve this goal, in this work were performed a lightweight and a heavyweight extension in the KDM metamodel, to analyze which one would present a better performance if used by Modernization Engineers. The evaluation of these extensions was performed by a case study that considered the modernization with aspects of a small-sized system. To evaluate the case study in both extensions, a set of comparison criteria were created to support the software engineers in choosing the best extension mechanism, according to their needs. In the context of this dissertation an experimental study were developed that aimed reproducing the scenarios that the modernization engineers had to perform maintenances and developing new refactorings in a aspect oriented KDM model. The experiment data considered the development time of the activities and the found number of errors. Finally, it was noticed that the extension mechanism to be choose will depend on the context that it will be applied, however, considering the approach studied here the best extension mechanism is the heavyweight one. / Manter sistemas legados é uma atividade complexa e onerosa para muitas empresas. Uma proposta recente para esse problema é a Modernização Dirigida à Arquitetura (Architecture-Driven Modernization - ADM), proposta pela OMG (Object Management Group). A ADM consiste em um conjunto de princípios e metamodelos padrões que apoiam a modernização de sistemas utilizando modelos. O Knowledge Discovery Metamodel (KDM) é o principal metamodelo da ADM, podendo representar diversos artefatos de um sistema, como código-fonte, arquitetura, interface de usuário, arquivos de configuração e processos de negócio. Em geral, sistemas legados possuem interesses transversais, apresentando problemas de entrelaçamento e espalhamento de código, o que eleva os custos de manutenção. A orientação a aspectos é uma alternativa para melhorar a modularização de interesses transversais. Mediante isso, neste trabalho é apresentado o termo Modernização Orientada a Aspectos que utiliza os conceitos da orientação a aspectos na ADM. Essa modernização consiste em remodularizar sistemas legados utilizando aspectos representados em nível de modelo. Para atingir esse objetivo, foi realizada uma extensão leve e outra pesada do metamodelo KDM, para analisar em qual das duas o desempenho dos engenheiros de modernização seria melhor. Para fazer a avaliação das extensões, foi realizado um estudo de caso levando em consideração a modernização com aspectos em um sistema de pequeno porte. Com o objetivo de avaliar o estudo de caso usando as duas extensões, foram desenvolvidos critérios de comparação que auxiliassem os engenheiros de software a escolher qual dos dois mecanismos de extensão utilizar em seu projeto. Foi feito também um estudo experimental que buscou reproduzir os cenários em que engenheiros de modernização tivessem que realizar manutenções e desenvolver novas refatorações em um modelo KDM orientado a aspectos. Os dados do experimento foram avaliados em relação ao tempo de desenvolvimento das atividades e quantidade de erros encontrados. Por fim, percebeu-se que o mecanismo de extensão a ser utilizado vai depender do contexto em que ele será aplicado, mas, para o domínio aqui estudado a extensão que melhor atendeu aos requisitos foi a pesada.

Context: Pre-project Requirements Engineering (RE) decisions are considered as very complex in Market Driven Requirements Engineering (MDRE). The complexity and economical impact of RE decisions motivates the need to support and understand RE decisions in MDRE. The purpose of Pre-project activities is to gather, analyze, select, and plan requirements for future releases of the software product in MDRE environment. Correct and timely pre-project decisions (for example initial requirements selection) are dependent on the quality and the availability of the provided decision material (for example requirements, business cases etc) for RE decisions. A Requirements Engineering framework called NORM (Needs Oriented Framework for Producing Requirements Decision Material) in collaboration with Ericsson AB is previously created with the intention of facilitating and speeding up the RE processes by ensuring that the right and sufficient decision material is available at the right time for pre-project RE decisions. NORM needs to be validated in software companies practicing MDRE in order to make it generally applicable in industry. Objectives: NORM framework was partially validated with informal interviews at one business unit within Ericsson AB but needed to be tested or validated in different environments (Telecom, e-commerce etc) in software industry to make sure that it becomes generally applicable in industry. The scope of this master's thesis is to investigate how to tailor NORM to improve a company's requirements engineering processes with the help of value stream mapping (VSM), and to evaluate the effort required and impact of this tailored process. Two MDRE based companies are chosen in this thesis work in order to validate NORM framework in software industry. Methods: There are two main research methods in this research work; Interviews and Document Analysis. In two MDRE based companies, we conducted interviews of employees involved in pre-project RE decision activities in a product, and accessed the requirements documents for the same product in order to initiate the NORM framework. Finally, an email was sent to the interviewees in both companies involved in RE with less than 10 questions in order to confirm our findings for validation of NORM framework. Results: With the information of initiation of NORM framework and using VSM we are able to chart the current decision points (DP) or decisions in the company’s RE process and the decision material that is used for each DP. We then have investigated what decision material is just enough, and when do a company need to produce it so that it is ready when the decision should be taken. We have looked at things such as waiting times, utilization and usefulness of produced decision material, and finally it is suggested to companies how their RE decision process in MDRE environment can be improved. Conclusions: Interviewees provided us the positive feedback on NORM, and they liked our novel research work in the form of NORM framework. Interviewees felt that the provided NORM structure of presenting pre-project decisions and its steps of identifying Appropriate Decision Material (ADM) is useful and usable, scalable and is according to industry relevance. It is concluded that the validation of NORM framework achieved positive feedback and results. / Blekinge Institute of Technology SE-371 79 Karlskrona Sweden Ph.: +46 455 38 50 00

<p>Oncogenic mutations in KRAS are present in approximately 95% of patients diagnosed with pancreatic ductal adenocarcinoma (<b>PDAC</b>) and are considered the initiating event during the development of pancreatic intraepithelial neoplasia (<b>PanIN</b>) precursor lesions. While it is well established that KRAS mutations can drive the initiation of pancreatic oncogenesis, the effects of oncogenic KRAS signaling on regulation of phosphatases during this process is not fully appreciated. Protein Phosphatase 2A (<b>PP2A</b>) has been implicated in suppressing KRAS-driven cellular transformation. However, low PP2A activity is observed in PDAC cells compared to non-transformed cells, suggesting that suppression of PP2A activity is an important step in the overall development of PDAC. In the current study, we demonstrate that KRASG12D induces the expression of both Cancerous Inhibitor of PP2A (<b>CIP2A</b>), an endogenous inhibitor of PP2A activity, and the PP2A target, c-MYC. Consistent with these findings, KRASG12D sequestered the specific PP2A subunit responsible for c-MYC degradation, B56a, away from the active PP2A holoenzyme in a CIP2A-dependent manner. During PDAC initiation <i>in vivo</i>, knockout of B56a promoted KRASG12D tumorigenesis by accelerating acinar-to-ductal metaplasia (<b>ADM</b>) and the formation of PanIN lesions. The process of ADM was attenuated <i>ex vivo</i> in response to pharmacological re-activation of PP2A utilizing direct small molecule activators of PP2A (<b>SMAP</b>s). Together, the results of this study suggest that suppression of PP2A-B56a through KRAS signaling can promote Myc-driven initiation of pancreatic tumorigenesis.</p>

A concentração de Fe, Ni, Cd, Mn, Zn, Cr e Pb, determinada por TXRF, foi investigada em matrizes de água, sedimento e fígados de peixes, amostrados em rios da região mineradora de carvão de Criciúma - SC/Brasil - afetadas por descargas de drenagem ácida de mina (DAM). A relação destes metais com a toxicidade para o bioindicador Daphnia magna (24 e 48 h) foi avaliada, sendo estabelecida correlação entre [Fe]solúvel e toxicidade à D. magna nas amostras de água. Para os sedimentos, há indícios de correlação dos teores de Fe e toxicidade, e nos fígados suspeita-se de níveis de Zn alterados. Efluentes da mineração, incluindo a DAM, após o tratamento por floculação e/ou decantação e/ou flotação e alcalinização mantiveram toxicidade mesmo com os metais reduzidos para concentrações não tóxicas à D. magna. Creditou-se a toxicidade remanescente a hidrocarbonetos policíclicos aromáticos (HPAs, determinada por CG/MS). Foram testados três adsorventes de baixo custo na retenção de metais (Fe, Ni, Cd, Mn, Zn, Cr e Pb) em soluções ácidas multimetais: casca de arroz (CA), carvão de casca de arroz (CCA) e turfa e carvão ativado comercial (CAC – adsorvente de confronto). As quantidades máximas adsorvidas dos metais (mg) por massa de sorbente (g) - qm, somatório dos metais, foram: CA 75,46 mg g-1; CAC 78,2 mg g-1; turfa 111,3 mg g-1 e CCA 137,49 mg g-1, (Langmuir e Freundlich - não linear). A toxicidade dos metais para D. magna destes eluatos foi reduzida. Foram preparados compósitos a partir de casca de arroz com deposição in situ de TiO2 (CCT – carbon covered with titanium), e testados como catalisador em Processos Oxidativos Avançados (POA). Os catalisadores TiO2 (P25 Degussa) e CCTs (25 e 50% de TiO2) em POA mostraram remoção dos HPAs e da toxicidade (D. magna e Scenedesmus subspicatus) nos efluentes de mineração, adequando os níveis de toxicidade à legislação ambiental vigente (Portaria FATMA 017/02) com resultados superiores do CCT. Assim, a presente tese alega que o uso de adsorventes à base de carvão de casca de arroz é capaz de reter os metais tipicamente presentes em efluentes ácidos (mineração de carvão), e que a toxicidade remanescente nestes efluentes, devida aos HPAs, pode ser reduzida pelo uso de POA, com incremento de eficiência quando o compósito CCT aqui desenvolvido é utilizado. / The concentration of Fe, Ni, Cd, Mn, Zn, Cr and Pb, determined by TXRF, was investigated in matrixes as water, sediment and fish liver, sampled at mining of coal region rivers from Criciúma - SC/Brazil – targets by acid mine drainage (ADM) discards. The relation of these metals with toxicity to Daphnia magna bioindicator (24 and 48 h) was evaluated, being established a correlation between [Fe]soluble and toxicity to D. magna in water samples. In sediments, correlation between Fe levels and toxicity was observed, and in liver Zn levels were altered. Mining effluents including AMD, after treatment by flocculation and/or decantation and/or flotation and alkalinization remain toxic even when metal concentrations had been reduced to levels which would be non toxic to D. magna. Residual toxicity was accounted to the presence of polycyclic aromatic hydrocarbons (PAHs, determined by GC/MS). Three low cost adsorbents were tested in metal retention (Fe, Ni, Cd, Mn, Zn, Cr and Pb) from multielemental acid solution: rice husk (RH), rice husk carbon (RHC), peat and commercial activated carbon (CAC – confront adsorbent). The maximum quantity of adsorbed metals (mg) by sorbent mass (g) - qm, as metals sum, were: CA 75.46 mg g-1; CAC 78.2 mg g-1; peat 111.3 mg g-1 and CCA 137.49 mg g-1, (Langmuir and Freundlich – non linear). The metal toxicity to D. magna of these eluates was reduced. Composites from rice husk with in situ deposition of TiO2 were synthesized (CCT – carbon covered with titanium), and tested as catalyst in advanced oxidative process (AOP). The catalysts TiO2 (P25 Degussa) and CCTs (25 e 50% de TiO2) in AOP showed PAHs and toxicity remotion (D. magna and Scenedesmus subspicatus) on mining effluents, adjusting toxicity levels to environmental legislation in force (FATMA 017/02), with best results to CCT. Then, the present thesis argues that rice husk carbon adsorbents is capable of retaining the metals typically presents in acid effluents (coal mining), and that remain toxicity in these effluents, from PAHs, can be reduced by AOP use, with efficient increasing when the composite here developed (CCT) is employed.

A concentração de Fe, Ni, Cd, Mn, Zn, Cr e Pb, determinada por TXRF, foi investigada em matrizes de água, sedimento e fígados de peixes, amostrados em rios da região mineradora de carvão de Criciúma - SC/Brasil - afetadas por descargas de drenagem ácida de mina (DAM). A relação destes metais com a toxicidade para o bioindicador Daphnia magna (24 e 48 h) foi avaliada, sendo estabelecida correlação entre [Fe]solúvel e toxicidade à D. magna nas amostras de água. Para os sedimentos, há indícios de correlação dos teores de Fe e toxicidade, e nos fígados suspeita-se de níveis de Zn alterados. Efluentes da mineração, incluindo a DAM, após o tratamento por floculação e/ou decantação e/ou flotação e alcalinização mantiveram toxicidade mesmo com os metais reduzidos para concentrações não tóxicas à D. magna. Creditou-se a toxicidade remanescente a hidrocarbonetos policíclicos aromáticos (HPAs, determinada por CG/MS). Foram testados três adsorventes de baixo custo na retenção de metais (Fe, Ni, Cd, Mn, Zn, Cr e Pb) em soluções ácidas multimetais: casca de arroz (CA), carvão de casca de arroz (CCA) e turfa e carvão ativado comercial (CAC – adsorvente de confronto). As quantidades máximas adsorvidas dos metais (mg) por massa de sorbente (g) - qm, somatório dos metais, foram: CA 75,46 mg g-1; CAC 78,2 mg g-1; turfa 111,3 mg g-1 e CCA 137,49 mg g-1, (Langmuir e Freundlich - não linear). A toxicidade dos metais para D. magna destes eluatos foi reduzida. Foram preparados compósitos a partir de casca de arroz com deposição in situ de TiO2 (CCT – carbon covered with titanium), e testados como catalisador em Processos Oxidativos Avançados (POA). Os catalisadores TiO2 (P25 Degussa) e CCTs (25 e 50% de TiO2) em POA mostraram remoção dos HPAs e da toxicidade (D. magna e Scenedesmus subspicatus) nos efluentes de mineração, adequando os níveis de toxicidade à legislação ambiental vigente (Portaria FATMA 017/02) com resultados superiores do CCT. Assim, a presente tese alega que o uso de adsorventes à base de carvão de casca de arroz é capaz de reter os metais tipicamente presentes em efluentes ácidos (mineração de carvão), e que a toxicidade remanescente nestes efluentes, devida aos HPAs, pode ser reduzida pelo uso de POA, com incremento de eficiência quando o compósito CCT aqui desenvolvido é utilizado. / The concentration of Fe, Ni, Cd, Mn, Zn, Cr and Pb, determined by TXRF, was investigated in matrixes as water, sediment and fish liver, sampled at mining of coal region rivers from Criciúma - SC/Brazil – targets by acid mine drainage (ADM) discards. The relation of these metals with toxicity to Daphnia magna bioindicator (24 and 48 h) was evaluated, being established a correlation between [Fe]soluble and toxicity to D. magna in water samples. In sediments, correlation between Fe levels and toxicity was observed, and in liver Zn levels were altered. Mining effluents including AMD, after treatment by flocculation and/or decantation and/or flotation and alkalinization remain toxic even when metal concentrations had been reduced to levels which would be non toxic to D. magna. Residual toxicity was accounted to the presence of polycyclic aromatic hydrocarbons (PAHs, determined by GC/MS). Three low cost adsorbents were tested in metal retention (Fe, Ni, Cd, Mn, Zn, Cr and Pb) from multielemental acid solution: rice husk (RH), rice husk carbon (RHC), peat and commercial activated carbon (CAC – confront adsorbent). The maximum quantity of adsorbed metals (mg) by sorbent mass (g) - qm, as metals sum, were: CA 75.46 mg g-1; CAC 78.2 mg g-1; peat 111.3 mg g-1 and CCA 137.49 mg g-1, (Langmuir and Freundlich – non linear). The metal toxicity to D. magna of these eluates was reduced. Composites from rice husk with in situ deposition of TiO2 were synthesized (CCT – carbon covered with titanium), and tested as catalyst in advanced oxidative process (AOP). The catalysts TiO2 (P25 Degussa) and CCTs (25 e 50% de TiO2) in AOP showed PAHs and toxicity remotion (D. magna and Scenedesmus subspicatus) on mining effluents, adjusting toxicity levels to environmental legislation in force (FATMA 017/02), with best results to CCT. Then, the present thesis argues that rice husk carbon adsorbents is capable of retaining the metals typically presents in acid effluents (coal mining), and that remain toxicity in these effluents, from PAHs, can be reduced by AOP use, with efficient increasing when the composite here developed (CCT) is employed.

Made available in DSpace on 2016-06-02T19:06:09Z (GMT). No. of bitstreams: 1 5515.pdf: 2859644 bytes, checksum: 8f2473af784eb07ff38067a957051dde (MD5) Previous issue date: 2013-08-27 / Universidade Federal de Sao Carlos / Software systems are considered legacy when they were developed many years ago with outdated technologies and their maintenance process consumes a large amount of resources. One cause of these problems is the inadequate modularization of its crosscutting concerns. In this situation, an alternative is to modernize the system with a new language to provide better support for concern modularization. ADM (Architecture-Driven Modernization) is an OMG model-driven proposal to modernize legacy systems and consist of a set of metamodels in which the main metamodel is KDM (Knowledge Discovery Metamodel), which allows to represent all the characteristics of a system. The modernization process begins with reverse engineering to represent the legacy system in a KDM model. Thereafter, refactorings can be applied to the model and then generate the modernized code. However, the current proposals do not support crosscutting concerns modularization. This occurs because the first step is to identify the elements which contribute with the implementation of a particular concern and it is not supplied by ADM. In this sense, this dissertation presents an approach for mining crosscutting concerns in KDM models, thus establishing the first step towards to a Concern-Driven modernization. The approach is a combination of two techniques, a concern library and a modified K-means clustering algorithm, which comprises four steps where the input is a KDM model and the result is the same KDM model with annotated concerns and some log files. In addition, we developed an Eclipse plugin called CCKDM to implement the approach. An evaluation was performed involving three software systems. The results show that for systems using APIs to implement their concerns the developed technique is an effective method for identifying them, achieving good values of precision and recall. / Sistemas de software são considerados legados quando foram desenvolvidos há muitos anos com tecnologias obsoletas e seu processo de manutenção consome uma quantidade de recursos além da desejada. Uma das causas desses problemas é a modularização inadequada de seus interesses transversais. Quando se encontram nessa situação, uma alternativa é modernizar o sistema para novas linguagens que forneçam melhor suporte à modularização desse tipo de interesse. A ADM (Architecture-Driven Modernization) é uma proposta do OMG para a modernização orientada a modelos de sistemas legados, sendo composta por um conjunto de metamodelos, em que o principal é o KDM (Knowledge Discovery Metamodel), que permite representar todas as particularidades de um sistema. O processo de modernização inicia-se com a engenharia reversa, em que o sistema legado é inteiramente representado em KDM. Depois disso, pode-se aplicar refatorações nesse modelo e gerar o código modernizado. Entretanto, a proposta atual da ADM não inclui suporte para modularizar interesses transversais de um sistema. Isso ocorre porque o primeiro passo desse processo é minerar e encontrar os elementos que contribuem para a implementação de um dado interesse, e isso não é fornecido pela ADM. Nesse sentido, nesta dissertação é apresentada uma abordagem para mineração de interesses no metamodelo KDM, estabelecendo o primeiro passo para um processo de modernização dirigido a interesses. A abordagem de mineração proposta atua com uma combinação de duas técnicas; uma biblioteca de interesses e um algoritmo modificado K-means para agrupar strings similares. A abordagem inclui quatro passos onde a entrada é um modelo KDM e o resultado é o mesmo modelo KDM com os interesses anotados e mais alguns arquivos de registro. Além disso, desenvolveuse um plugin chamado CCKDM para o ambiente Eclipse que implementa a abordagem. Uma avaliação foi realizada envolvendo três sistemas de software. Os resultados da avaliação mostraram que para sistemas que utilizam APIs para implementar seus interesses a técnica desenvolvida é efetiva para a identificação deles, atingindo bons valores de precisão e cobertura.

A concentração de Fe, Ni, Cd, Mn, Zn, Cr e Pb, determinada por TXRF, foi investigada em matrizes de água, sedimento e fígados de peixes, amostrados em rios da região mineradora de carvão de Criciúma - SC/Brasil - afetadas por descargas de drenagem ácida de mina (DAM). A relação destes metais com a toxicidade para o bioindicador Daphnia magna (24 e 48 h) foi avaliada, sendo estabelecida correlação entre [Fe]solúvel e toxicidade à D. magna nas amostras de água. Para os sedimentos, há indícios de correlação dos teores de Fe e toxicidade, e nos fígados suspeita-se de níveis de Zn alterados. Efluentes da mineração, incluindo a DAM, após o tratamento por floculação e/ou decantação e/ou flotação e alcalinização mantiveram toxicidade mesmo com os metais reduzidos para concentrações não tóxicas à D. magna. Creditou-se a toxicidade remanescente a hidrocarbonetos policíclicos aromáticos (HPAs, determinada por CG/MS). Foram testados três adsorventes de baixo custo na retenção de metais (Fe, Ni, Cd, Mn, Zn, Cr e Pb) em soluções ácidas multimetais: casca de arroz (CA), carvão de casca de arroz (CCA) e turfa e carvão ativado comercial (CAC – adsorvente de confronto). As quantidades máximas adsorvidas dos metais (mg) por massa de sorbente (g) - qm, somatório dos metais, foram: CA 75,46 mg g-1; CAC 78,2 mg g-1; turfa 111,3 mg g-1 e CCA 137,49 mg g-1, (Langmuir e Freundlich - não linear). A toxicidade dos metais para D. magna destes eluatos foi reduzida. Foram preparados compósitos a partir de casca de arroz com deposição in situ de TiO2 (CCT – carbon covered with titanium), e testados como catalisador em Processos Oxidativos Avançados (POA). Os catalisadores TiO2 (P25 Degussa) e CCTs (25 e 50% de TiO2) em POA mostraram remoção dos HPAs e da toxicidade (D. magna e Scenedesmus subspicatus) nos efluentes de mineração, adequando os níveis de toxicidade à legislação ambiental vigente (Portaria FATMA 017/02) com resultados superiores do CCT. Assim, a presente tese alega que o uso de adsorventes à base de carvão de casca de arroz é capaz de reter os metais tipicamente presentes em efluentes ácidos (mineração de carvão), e que a toxicidade remanescente nestes efluentes, devida aos HPAs, pode ser reduzida pelo uso de POA, com incremento de eficiência quando o compósito CCT aqui desenvolvido é utilizado. / The concentration of Fe, Ni, Cd, Mn, Zn, Cr and Pb, determined by TXRF, was investigated in matrixes as water, sediment and fish liver, sampled at mining of coal region rivers from Criciúma - SC/Brazil – targets by acid mine drainage (ADM) discards. The relation of these metals with toxicity to Daphnia magna bioindicator (24 and 48 h) was evaluated, being established a correlation between [Fe]soluble and toxicity to D. magna in water samples. In sediments, correlation between Fe levels and toxicity was observed, and in liver Zn levels were altered. Mining effluents including AMD, after treatment by flocculation and/or decantation and/or flotation and alkalinization remain toxic even when metal concentrations had been reduced to levels which would be non toxic to D. magna. Residual toxicity was accounted to the presence of polycyclic aromatic hydrocarbons (PAHs, determined by GC/MS). Three low cost adsorbents were tested in metal retention (Fe, Ni, Cd, Mn, Zn, Cr and Pb) from multielemental acid solution: rice husk (RH), rice husk carbon (RHC), peat and commercial activated carbon (CAC – confront adsorbent). The maximum quantity of adsorbed metals (mg) by sorbent mass (g) - qm, as metals sum, were: CA 75.46 mg g-1; CAC 78.2 mg g-1; peat 111.3 mg g-1 and CCA 137.49 mg g-1, (Langmuir and Freundlich – non linear). The metal toxicity to D. magna of these eluates was reduced. Composites from rice husk with in situ deposition of TiO2 were synthesized (CCT – carbon covered with titanium), and tested as catalyst in advanced oxidative process (AOP). The catalysts TiO2 (P25 Degussa) and CCTs (25 e 50% de TiO2) in AOP showed PAHs and toxicity remotion (D. magna and Scenedesmus subspicatus) on mining effluents, adjusting toxicity levels to environmental legislation in force (FATMA 017/02), with best results to CCT. Then, the present thesis argues that rice husk carbon adsorbents is capable of retaining the metals typically presents in acid effluents (coal mining), and that remain toxicity in these effluents, from PAHs, can be reduced by AOP use, with efficient increasing when the composite here developed (CCT) is employed.

L’ADKP est la 5e cause de décès par cancer dans le monde occidental, et il est estimé qu’il constituera la 2e cause de mort par cancer d’ici à 2030. Le taux de survie à 5 ans est inférieur à 4%, et la médiane de survie est d’environ 6 mois. Ce pronostic sombre est dû à une pathologie asymptomatique dans les phases précoces du développement tumoral, résultant en un diagnostic tardif. Les tumeurs primaires sont constituées de structures épithéliales néoplasiques entourées par un stroma abondant empêchant l’accès des chimiothérapies aux cellules tumorales. La compréhension des mécanismes d’initiation et de progression tumorale est donc primordiale pour développer de nouvelles stratégies visant à la détection et à la prise en charge thérapeutique optimale des patients atteints d’ADKP. Le TGFbeta est une cytokine assurant de nombreuses fonctions physiologiques comme la régulation de l’immunité, la cicatrisation, le développement ou encore l’angiogenèse. Les résultats présentés dans ce manuscrit mettent en évidence que l’activation de la voie de signalisation TGFbeta perturbe la différenciation des cellules acineuses au cours du développement, et perturbe l’identité acineuse lorsqu’elle est activée dans le pancréas chez l’adulte. L’induction en parallèle de l’apoptose des cellules acineuses et d’une métaplasie acino-canalaire (ou ADM) mène à la disparition quasi-totale du tissu acineux au profit de structures canalaires typiques d’un pancréas en régénération. Lorsque l’oncogène KRASG12D est exprimé en parallèle dans le tissu pancréatique chez l’adulte, ce tissu canalaire régénératif est mis à profit par KRAS pour le développement précoce de lésions pré-néoplasiques. Mes travaux au sein de l’équipe du Dr. Laurent BARTHOLIN permettent donc de démontrer in vivo un nouveau rôle du TGFbeta dans la carcinogénèse pancréatique / PDA is the 5th cause of cancer related death in the western countries, and is estimated to move the second rank by 2020. The 5-year survival rate is less than 4%, and the median survival is around 6 months. The poor prognostic of this tumor is due to asymptomatic early phases of the disease, resulting in a late diagnosis. Primary tumors are composed by ductal neoplastic lesions embedded into a highly abundant stroma that prevents the access of chemotherapeutic drugs to the tumor cells. Thus, understanding tumor initiation and progression mechanisms is needed to develop new strategies aiming at detecting and taking care of patients in the most optimal manner. TGFbeta is a cytokine playing several physiological functions such as immunity regulation, wound healing, development or angiogenesis. Results presented in this manuscript demonstrate that activation of TGFbeta signaling disturb acinar cell differentiation during development, and disrupts acinar cell identity when activated in the adult pancreas. The simultaneous induction of acinar cell apoptosis and ADM leads to the massive loss of acinar cells and the emergence of ductal structures typical of pancreas regeneration. When the KRASG12D oncogene is expressed in combination with the activation of TGFbeta signaling, these regenerative duct structures are harnessed by KRASG12D to develop early neoplastic lesions. Thus, my work in Dr. Laurent BARTHOLIN’s team demonstrates a new function of TGFbeta in pancreatic carcinogenesis in vivo

Unternehmen agieren heute in einer hochdynamischen Umwelt, wodurch die Anforderungen an Business Intelligence-Systeme (BI-Systeme) sich stetig verändern. Durch zügiges Reagieren darauf können sich Unternehmen Wettbewerbsvorteile verschaffen. Die dazu notwendige Wandlungsfähigkeit von BI-Systemen setzt voraus, dass bereits die BI-Architektur auf Flexibilität ausgelegt ist. Die Anwendung des Paradigmas der modellgetriebenen Softwareentwicklung auf die Domäne des Data Warehouse Engineerings (DWE) kommt diesem Bedarf nach. Zudem muss neben der Agilität von BI-Systemen auch der Faktor der Korrektheitsprüfung nach vorgenommenen Änderungen betrachtet werden. Es soll untersucht werden, inwieweit sich die im modellgetriebenen DWE anfallenden Metadaten zur Unterstützung und Automatisierung von Softwaretests zur Korrektheitsprüfung nutzen lassen. Die so erzielte Verringerung des Überprüfungsaufwandes führt zu einer verbesserten Wandlungsfähigkeit von BI-Architekturen und kommt somit dem Bedarf von effizienten agilen BI-Lösungen nach.

Automated decision making (ADM) is not a new phenomenon within public administration. Millions of automated decisions are made each year, including matters on parental benefits, social security benefits and income tax. ADM is used increasingly within both government agencies and municipal agencies. In light of this development, it becomes vital to have legal mechanisms in place which ensure transparency in automated decision making. This is to make sure that decisions are correct and that the systems work in compliance with procedural safeguards such as objectivity and impartiality. This begs the question of whether new legal solutions are needed to secure transparency of automated decisions. Current ADM systems within public administration are based on static algorithms that cannot change unless they are programmed to do so. Robotic Process Automation (RPA) is such a technology, commonly used by municipal agencies. Given the development within artificial intelligence (AI), ADM systems based on AI might be the next step. Then again, taking into account the extensive problems with the non-transparency of the “black box” of AI makes this technology rather unfit for decision making within public administration. The legal system provides different ways for citizens to obtain insight into and control of public administration. The principle of public access to information provides a right for all to access official documents. The Administrative Procedure Act (2017:900) provides access to information for the party concerned with a matter and the General Data Protection Regulation (GDPR) of the EU gives a right to information for data subjects. These rights to information can be restricted, for example by provisions on secrecy. However, the legal rights to information do not secure a comprehensive or direct transparency of the workings of ADM systems within public administration. The kind of transparency provided is rather a transparency by proxy, an indirect transparency that substitutes for a direct and functional one. For example, the provisions of the Administrative Procedure Act are not adapted to ADM, and the application of the right to access official documents entails inconsistencies. If information is provided to a citizen, there is no guarantee of understanding for example a description of an algorithm. To create a direct and functional transparency of automated decisions and the workings of ADM systems, it is vital for law and technology to evolve in interplay. A general discussion of public access to ADM systems and their implications on public trust and the rule of law is also of the essence.