Submitted by Nadir Basilio (nadirsb@uninove.br) on 2017-05-22T17:57:59Z No. of bitstreams: 1 Paulo Ferreira Guimaraes.pdf: 2675378 bytes, checksum: a280aaa9dfb80451dede9aeeb5020a24 (MD5) / Made available in DSpace on 2017-05-22T17:57:59Z (GMT). No. of bitstreams: 1 Paulo Ferreira Guimaraes.pdf: 2675378 bytes, checksum: a280aaa9dfb80451dede9aeeb5020a24 (MD5) Previous issue date: 2017-02-20 / This research, through a case study carried out in a company providing services in the audiovisual area, sought, through the application of sustainable project management, to analyze the influence of innovations on ecoefficiency in events, especially corporate events. The event sector begins to move towards sustainable events, in which the use of recycling techniques, selective collection of waste, conscious use of water, even more with the current water crisis, become increasingly common practices and that corroborate to satisfy the concept of the Triple Bottom Line (TBL). In order to anticipate and mitigate to the maximum the problems that negatively affect and influence the TBL, this study proposed a prior analysis of what is possible to mitigate during the execution of the event and not only treat the post-event, that is. After the generation of waste. One of the ways to achieve this goal is through innovations, which are presented in a dynamic way and promote a constant evolution, whether in equipment or processes. The application of these innovations was the object of study in this work, with the intention of showing how they can be applied to help in the ecoefficiency of the events. With a comparative approach between solutions and equipment that do not use innovations aligned with sustainable demands and others that have such requirements, we sought to analyze how innovations can collaborate with events to become more assertive about what we all seek, not Only in events, but for our planet, which is to use resources in a rational way, so that it does not compromise the needs of future generations. The case study developed through a qualitative and exploratory research sought to find correlations between the innovations and their potential to add value, both to clients contracting the events and to the participants of the same, either through the return on the investment made or through the perception of value observed by the participating public. As a basis for this study framework, several measurements were carried out and analyzed, comparing the proposed solutions, analyzing their collaborative potential for ecoefficiency in events. The main result was a total collaboration of the eco-efficient innovations proposed for sustainability in events. The analyzes showed that all the innovations proposed were totally satisfactory in the two dimensions that cover eco-efficiency, that is, the environmental and the economic. / Esta pesquisa, por intermédio de um estudo de caso realizado em uma empresa prestadora de serviços na área de audiovisual, buscou, por meio da aplicação da gestão de projetos sustentáveis, analisar a influência das inovações sobre a ecoeficiência em eventos, em especial eventos corporativos. O setor de eventos começa a ter uma movimentação em busca de eventos sustentáveis, nos quais o uso de técnicas de reciclagem, coleta seletiva de resíduos, uso consciente das águas, ainda mais com a crise hídrica atual, tornam-se práticas cada vez mais usuais e que corroboram para satisfazer o conceito do Triple Bottom Line (TBL). Com o objetivo de se antecipar e mitigar ao máximo os problemas que atingem e influenciam de forma negativa o TBL, este estudo propôs uma análise prévia do que é possível se mitigar durante a execução do evento e não tratar somente o pós-evento, ou seja, após a geração dos resíduos. Uma das formas de alcançar este objetivo é por meio das inovações, as quais se apresentam de forma dinâmica e promovem uma constante evolução, sejam elas nos equipamentos ou nos processos. A aplicação dessas inovações foi o objeto de estudo neste trabalho, com o intuito de mostrar como as mesmas podem ser aplicadas para ajudar na ecoeficiência dos eventos. Com uma abordagem comparativa entre soluções e equipamentos que não utilizam inovações alinhadas com as demandas sustentáveis e outros que possuam tais requisitos, buscou-se analisar como as inovações podem colaborar com os eventos para que se tornem mais assertivos em relação ao que todos buscamos, não só nos eventos, mas sim para o nosso planeta, que é utilizar os recursos de forma racional, para que não se comprometa as necessidades das gerações futuras. O estudo de caso desenvolvido por meio de uma pesquisa qualitativa e exploratória procurou encontrar correlações entre as inovações e seu potencial de agregar valor, tanto aos clientes contratantes dos eventos como aos participantes dos mesmos, seja por meio do retorno sobre o investimento realizado ou pela percepção de valor observada pelo público participante. Como base deste arcabouço de estudo foram realizadas e analisadas diversas medições, comparando as soluções propostas, analisando seu potencial colaborativo à ecoeficiência em eventos. Como principal resultado, identificou-se uma total colaboração das inovações ecoeficientes propostas para a sustentabilidade em eventos. As análises desenvolvidas mostraram que todas as inovações propostas foram totalmente satisfatórias nas duas dimensões que abrangem a ecoeficiência, ou seja, a ambiental e a econômica.

A epistasia tem sido considerada como um componente importante da herança de caracteres quantitativos, estando presente nos componentes de variância e covariância genética. No entanto, por ser desconsiderada na maioria dos modelos genético-estatísticos, seu impacto nos programas de melhoramento ainda é pouco conhecido. Além disso, como os programas de melhoramento de milho, em especial no Brasil, têm realizado seleção sob condições de estresse hídrico, é importante analisar o efeito desse estresse sobre a epistasia. Assim, este trabalho teve como objetivo a análise genética de caracteres quantitativos em milho, incluindo epistasia e epistasia pleiotrópica, em ambientes contrastantes para estresse hídrico. Foi utilizado o delineamento triple test cross modificado com testadores, em que cem progênies F2:3 foram retrocruzadas com suas linhagens genitoras L-08-05F e L-38-05D e sua geração F1. Posteriormente, as 300 progênies de retrocruzamento foram cruzadas com duas linhagens testadoras, L-02-03D e L-04-05F. Os testecrosses foram avaliados em dez ambientes no município de Piracicaba/SP, sendo cinco ambientes sem estresse hídrico e cinco com estresse hídrico, utilizando o delineamento α-látice em esquema fatorial com duas repetições por ambiente. Os caracteres analisados foram produção de grãos (PG), acamamento e quebramento de plantas (ACQ), prolificidade (PROL), altura da planta (AP) e da espiga (AE), posição relativa da espiga (PRE), florescimento masculino (FM) e feminino (FF) e intervalo entre florescimentos (IF). A presença de epistasia foi detectada para todos os caracteres. No entanto, os grupos de ambientes, sem e com estresse hídrico, e os diferentes testadores afetaram a detecção de epistasia para todos os caracteres, com exceção de PG, PROL e AP em que a epistasia foi detectada em todas as análises de variâncias conjuntas. A interação epistasia x grupos de ambientes foi significativa apenas para os caracteres PG e PROL dos testecrosses provenientes do testador L-02-03D (TC1) e AP e AE dos testecrosses provenientes do testador L-04-05F (TC2), enquanto que, a interação epistasia x testadores foi significativa para todos os caracteres. Os efeitos epistáticos de testecrosses referentes às plantas F2 significativos foram bidirecionais, com exceção do caráter PROL do TC2 no grupo de ambientes com estresse hídrico, em que os efeitos foram unidirecionais e positivos. Além disso, para cada testador e grupo de ambientes foram detectados efeitos epistáticos significativos para um grupo específico de testecrosses, ocorrendo variações na magnitude e/ou sinais dos testecrosses coincidentes. A presença de epistasia pleiotrópica foi detectada entre diversos pares de caracteres e, além disso, foi observada a formação de agrupamentos de caracteres relacionados, indicando que a epistasia pleiotrópica é modular, porém sofre influência do ambiente, presença ou ausência de estresse hídrico, e dos testadores. Portanto, na população analisada, a epistasia é um componente importante tanto da variância genética de caracteres quantitativos como da covariância genética entre caracteres, indicando que não considerá-la nas análises pode resultar em interpretações que não refletem a real complexidade do controle genético destes caracteres. / Epistasis has been considered an important part of quantitative traits inheritance and it is present in the components of genetic variance and covariance. However, its impact on breeding programs is still little-known because it is disregarded in most statistical genetic models. In addition, maize breeding programs, especially in Brazil, have been practicing selection under water stress conditions, so it is important to analyze the effects of these environments on epistasis. In this context, the objective of this study was to perform a genetic analysis of quantitative traits in maize, including epistasis and pleiotropic epistasis, in contrasting environments for water stress. The modified triple test cross design with testers was used, in which 100 F2:3 progenies were backcrossed to their parental inbred lines, L-08-05F and L-38-05D, and their F1 generation. Thereafter, the 300 backcrossed progenies were testcrossed to the inbred lines testers L-02-03D and L-04-05F. The testcrosses were evaluated in Piracicaba, SP, Brazil, in ten environments, which five environments presented water stress and the other five not, in an α-lattice design on a factorial scheme with two replications by environment. The analyzed traits were grain yield (GY), root and stalk lodging (PL), ear per plant (EPP), plant height (PH), ear height (EH), ear placement (EP), days to anthesis (DA), days to silking (DS) and anthesis-silking interval (ASI). Epistasis was detected for all traits. However, the environmental groups and the different testers affected epistasis detection for all traits, except for GY, EPP and PH, in which epistasis was detected in all joint analysis of variance. The interaction epistasis x environments groups was significant only for GY and EPP of testcrosses from the tester L-02-03D (TC1) and PH and EH of testcrosses from the tester L-04-05F (TC2), whereas the interaction epistasis x testers was significant for all traits. The significant epistatic effects of testcrosses referring to F2 plants were bidirectional, except for EPP of TC2 in the water stress environmental group, where the effects were unidirectional and positives. Besides that, for each tester and environmental group, significant epistatic effects for a specific group of testcrosses were detected, occurring variation in magnitude and/or sign of coincident testcrosses. Pleiotropic epistasis was detected between many pairs of traits and it was observed formation of related traits clusters, suggesting that pleiotropic epistasis is modular, but the modules suffered influence of environments and testers. Therefore, in the population analyzed, epistasis is an important component of genetic variance of quantitative traits and also of genetic covariance between traits, showing that disregarding epistasis in analyses may result in interpretations that do not reflect the real complexity of the genetic control of these traits.

A adoção de rotas tecnológicas ambientalmente sustentáveis é uma estratégia acertada para empresas que queiram manter ou melhorar suas posições de mercado e contribuir para a prevenção e adaptação às mudanças climáticas globais. É nessa perspectiva da inovação e da sustentabilidade que este estudo avaliou a influência da cooperação em P&D e das ecoinovações sobre o desempenho socioeconômico de 221 fabricantes de produtos elétricos e eletrônicos. As teorias de Gaia, do Holismo e a teoria evolucionária da inovação predominantemente orientaram o estudo. Os dados foram coletados em 2017 e processados via SmartPLS®3. Por meio da técnica de Modelagem de Equações Estruturais o modelo conceitual do estudo foi validado com 99% de confiabilidade (p<0,01), demonstrando com originalidade que a cooperação em P&D e as ecoinovações explicaram satisfatoriamente em 51,3%o desempenho socioeconômico das empresas pesquisadas. Três hipóteses comprovaram que a cooperação em P&D com parceiros tecnológicos influenciou positivamente a introdução de ecoinovações de produto, ecoinovações de processo e ecoinovações organizacionais nas empresas investigadas. Duas hipóteses comprovaram que ecoinovações de produto e ecoinovações organizacionais influenciaram positivamente o desempenho socioeconômico das empresas. Uma hipótese não comprovada demonstrou que ecoinovações de processo não influenciaram positivamente o desempenho socioeconômico das empresas. Dos atributos de ecoinovação, três não foram validados estatisticamente: a simplificação das embalagens, a simplificação da construção e a eficiência energética dos produtos desenvolvidos. Apesar de os atributos não validados demonstrarem atraso tecnológico dos produtos elétricos e eletrônicos, há predominância de uma rota tecnológica ambientalmente sustentável nas empresas, o que é um visível diferencial competitivo. São notáveis as implicações deste estudo a partir dos emergentes paradigmas da economia circular e da economia verde. Se cooperação em P&D e ecoinovações permitiram resultados socioeconômicos satisfatórios, em empresas distintas usuárias de minerais e de energia elétrica, então cai por terra o paradigma da inovação poluidora, que ignora que recursos naturais são finitos. Fica evidente que o paradigma Triple Bottom Line, que considera o equilíbrio entre as dimensões ambiental, social e econômica, possui base viável para a indústria do terceiro milênio. Emerge nas empresas a responsabilidade de ancorar a mudança tecnológica em todos os elos de suas cadeias de valor, desde a extração de matérias primas da natureza até a educação de consumidores para o uso e descarte consciente de produtos. É possível sugerir que não corrigir a rota tecnológica baseada no paradigma econômico dos excessos sobre os recursos planetários pode ser qualificado como responsabilidade corporativa de lesa ao Planeta. Ademais, indústrias e cadeias de valor de base poluidora parecem estar fadadas ao desaparecimento. Os resultados deste estudo são restritos à amostra de indústrias investigadas no Brasil. Temas com potencial de pesquisa emergem em simbiose e biomimética industrial, sistemas de ecoinovação em Smart Cities, ecoinovação social, ecoinovação de marketing e ecoinovações na Indústria 4.0. / The adoption of environmentally sustainable technology routes is a sound strategy for companies that want to maintain or improve their market positions and contribute to the prevention and adaptation to global climate change. In this perspective of innovation and sustainability, this study evaluated the influence of cooperation in R & D and of eco-innovations on the socioeconomic performance of 221 manufacturers of electric and electronic products. The theories of Gaia, Holism and the evolutionary theory of innovation predominantly guided the study. Data were collected in 2017 and processed via SmartPLS®3. Through the Structural Equation Modeling technique, the conceptual model of the study was validated with 99% reliability (p<0,01), showing with originality that the cooperation in R & D and the eco-innovations satisfactorily explained the socio-economic performance of the companies surveyed in 51.3%.Three hypotheses have proved that cooperation in R & D with technological partners positively influenced the introduction of product eco-innovations, process eco-innovations and organizational eco-innovations in the companies investigated. Two hypotheses have shown that product eco-innovations and organizational eco-innovations have positively influenced the companies\' socioeconomic performance. An unproven hypothesis showed that process eco-innovation has not positively influenced the companies\' socioeconomic performance.From the eco-innovation attributes, three have not been statistically validated: the simplification of packaging, the simplification of construction and the energy efficiency of developed products. Although the non-validated attributes demonstrate technological backwardness of the electrical and electronic products, there is a predominance of an environmentally sustainable technological route in companies, which is a visible competitive edge. The implications of this study are noteworthy from the emerging paradigms of the circular economy and of the green economy. If cooperation in R & D and eco-innovations have enabled satisfactory socioeconomic outcomes, in companies which are distinct users of minerals and electricity, then it falls down the paradigm of polluting innovation that ignores that natural resources are finite. It is clear that the Triple Bottom Line paradigm, which considers the balance between the environmental, social and economic dimensions, has a viable basis for the industry of the third millennium. Companies have the responsibility to anchor technological change at every link in their value chains, since the extraction of raw materials from nature up to the education of consumers for the conscious use and disposal of products. It is possible to suggest that not correcting the technological route based on the economic paradigm of excesses on the world\'s resources can be qualified as a harmful corporate responsibility to the Planet.In addition, polluter-based industries and value chains seem to be doomed to disappear. The results of this study are restricted to the sample of industries investigated in Brazil. Topics with potential for future research emerge in symbiosis and industrial biomimetics, eco-innovation systems in Smart Cities, social eco-innovation, marketing eco-innovation and eco-innovations in Industry 4.0.

Il est généralement admis que le cancer du sein représente un ensemble de plusieurs maladies, définies comme des sous-types ayant des caractéristiques moléculaires et cliniques qui leurs sont propres. Une meilleure compréhension des mécanismes qui sous-tendent l'hétérogénéité du cancer du sein est essentielle au développement de thérapies mieux ajustées. Le concept de cellules souches cancéreuses (CSC) pourrait être un des clés de cette compréhension. A ce jour, un certain nombre de marqueurs ont été proposés pour isoler et caractériser les cellules souches dans le cancer du sein, mais aucun ne semble totalement satisfaisant.Le but de mon travail était de déterminer un marqueur ou une combinaison de marqueurs avec lesquels les fractions enrichies en CSC pourraient être isolées de manière reproductible dans le cancer du sein de sous-types basal (BLBC). En effet, les tumeurs basales représentent 15% de toutes les tumeurs mammaires, mais constituent le sous-type le plus agressif. À cet effet, j'ai analysé un certain nombre de marqueurs par analyse FACS et tri cellulaire et utilisé la capacité de formation de mammosphères (MS) comme critère de validation pour la présence de CSC. Les lignées cellulaires utilisées comme modèles étaient les SUM 159, MDA-MB-231, MDA-MB-436, HCC1143, MDA-MB-468, Hs578T et BT-549 correspondant aux modèles basal-A et B. J'ai également testé trois lignées luminales les MCF7, T47D et BT474.De tous les marqueurs testés, seules, la combinaison des protéines de surface cellulaire CD44/CD24/EpCAM et l’activité enzymatique ALDH élevée ont permis d’obtenir un enrichissement significatif en CSC. Toutefois, le niveau de l'activité ALDH est apparu inconstant d’une lignée cellulaire à une autre et selon le type de tumeurs. D'autres marqueurs membranaires ont donné des résultats mitigés dans le cancer du sein ER-. En effet, la plupart des lignées basales ont montré des profils FACS assez homogènes avec des proportions élevées de cellules CD44+. Cependant, l'association de la positivité de CD44 avec l'EMT et la souchitude, ainsi que la bonne corrélation observée dans les modèles luminaux de la population de cellules CD44+/CD24- avec l’enrichissement en CSC, nous a incité à déterminer si le niveau d'expression en CD44 faisait une différence dans les tumeurs basales. Sur cette base, j’ai montré que les cellules CD44 high présentent une forte capacité à former des MS dans toutes les lignées cellulaires testées. Cette constatation nous a incités à utiliser CD44high vs. CD44low comme critère de tri cellulaire et à utiliser ces fractions pour effectuer une analyse du transcriptome afin d'identifier d'autres marqueurs non encore déterminés, pouvant isoler des fractions cellulaires plus faibles avec un enrichissement plus élevé en CSC. / It is now accepted that breast cancer is a compendium of several diseases defined as subtypesthat are associated with different clinical outcomes and molecular characteristics. A betterunderstanding of the mechanisms underlying breast cancer heterogeneity is critical to the development of better adjusted therapies. One of the keys to breast cancer heterogeneity may be explained by cancer stem cells (CSC). A number of markers have been proposed to isolate and characterize breast cancer stem cells, but none appears totally satisfactory.The purpose of my work was determine a marker or combination of markers with which CSC enriched fractions could be reproducibly isolated in basal like breast cancer (BLBC). BLBC represent 15% of all breast tumors, but are the most aggressive subtype. To this aim, I have analyzed a number of markers by FACS analysis and cell sorting and used the capacity to form mammospheres (MS) as a validation criterion for the presence of CSCs. The cell lines used as models were SUM 159, MDA-MB-231, MDA-MB-436, HCC1143, MDA-MB-468, Hs578T and BT-549 comprising both Basal A and Basal B models. I also tested three luminal models MCF7, T47D and BT474.Of all the markers tested those that most consistently allowed enrichment of CSCs were the combination of cell surface proteins CD44/CD24/EpCAM and elevated ALDH enzyme activity. However, ALDH activity appeared irregular, ranging from good to inconsistent according to the cell line. Other cell surface markers gave mixed results in ER- breast cancer because the elevated fraction of CD44+ cells found in most of basal breast cancer cell lines and their propensity to show rather homogenous FACS labeling patterns. However, the association of CD44 positivity with EMT and stemness, as well as the good correlation, we observed in luminal models, of CD44+/CD24- cell population with CSC enrichment incited us to determine whether the level of expression of CD44 could make a difference in basal like models. I show that CD44high cells present higher capacity to form MS in all cell line models tested. This prompted us to use CD44high vs. CD44low as a cell sorting criterion and use these fractions to perform transcriptome analysis in order to identify other markers yet not determined, that may point to smaller cell fractions with a higher CSC enrichment.

Nos travaux se focalisent sur l’impact des hétérogénéités structurales sur la diffusion de l’hydrogène dans les métaux. Dans ce cadre, des essais de perméation sont simulés par la méthode des éléments finis, afin de comprendre l’impact des caractéristiques métallurgiques sur les données extraites lors de ce type d’analyse. Afin de pouvoir séparer les différents mécanismes intervenant lors de la diffusion, l’étude est conduite en plusieurs étapes. A l’échelle de la membrane, les effets du piégeage et de la présence d’une couche d’oxyde à la surface du matériau sont considérés. Tandis que le piégeage et la couche d’oxyde diminuent tous deux la diffusivité effective, leurs effets sont opposés sur les concentrations en hydrogène en subsurface mesurées. D’autre part, les effets du piégeage lors de la désorption de l’hydrogène sont plus particulièrement étudiés. Il s’avère nécessaire de prendre en considération les fréquences de saut des atomes d’hydrogène afin de se rapprocher des données expérimentales. Ces premières études ayant portées sur des membranes homogènes, nous nous sommes consacrés, dans une dernière partie, aux effets de la microstructure sur la diffusion. Pour cela, nous considérons l’influence des joints de grains dits « généraux », qui se comportent comme des courts-circuits de diffusion pour l’hydrogène. La microstructure entraîne l’apparition d’effets d’échelle, lorsque l’épaisseur de la membrane se rapproche de la taille de grains. Qui plus est, en considérant un modèle à trois dimensions, les triples joints amplifient ces effets d’échelle, notamment dans le cas de matériaux nanocrystallins. / Our work focuses on the impact of structural heterogeneities on the diffusion of hydrogen in metals. In this context, permeation tests are simulated using the finite element methods, to understand the effects of the metallurgical properties on the data extracted with such analysis. To separate the different mechanisms occurring during diffusion, the study is led by several steps. At the scale of the membrane, the effects of trapping and the presence of an oxide layer at the surface of the material are considered. While the trapping and the surface layer both slow down the effective diffusivity, their effects are opposed on the measured hydrogen subsurface concentrations. On the other hand, the effects of trapping during the desorption are more specifically studied. It appears that taking into account the jump frequencies of the hydrogen atoms is required to get closer to the experimental data. Since the first studies dealt with homogeneous membranes, we focus in a last part on the effects of the microstructure on hydrogen diffusion. To do so, we consider the influence of “random” grain boundaries, acting as hydrogen diffusion short-circuits. Scale effects appear due to the microstructure when the membrane thickness approaches the grain size. Moreover, by using a three-dimensional model, triple junctions emphasize the scale effects, especially for nanocrystalline materials.

De nombreuses applications comme les cartes bancaires manipulent des données confidentielles. A ce titre, les circuits microélectroniques qui les composent, font de plus en plus l'objet d'attaques représentant des menaces pour la sécurité. De plus, un grand nombre des circuits électroniques portables et fonctionnant sur batterie demandent que la consommation électrique soit toujours plus réduite. Les concepteurs de circuit doivent donc proposer des solutions sécurisées, tout en limitant la consommation.Ce travail présente l'évaluation sécuritaire et la conception de contre-mesures pour des architectures à triple-caisson dédiées à la réduction de la consommation. Ces recherches, liées au contexte, se sont focalisées sur l'évaluation de cette architecture face à des injections de fautes Laser. Dès le début de ce manuscrit, l’état de l’art de l’injection de fautes est développé, en se focalisant sur les effets physiques d’un faisceau laser. Les architectures à double et triple-caisson sont ensuite analysées dans le but de comparer leur robustesse. Cette démarche permet d’appréhender d’éventuels effets physiques induits par le laser à l’intérieur des caissons de polarisations Nwell, Pwell et des transistors MOS. Suite à cette analyse des phénomènes physiques, des modélisations électriques des portes CMOS ont été développées pour des architectures à double et triple-caisson. De bonnes corrélations ont pu être obtenues entre les mesures et les simulations électriques. Pour conclure, ce travail a permis d'extraire de potentielles règles de conception permettant d’améliorer la robustesse sécuritaire des portes CMOS et de développer des moyens de détections d’attaques lasers. / In many applications such as credit cards, confidential data is used. In this regard, the systems-on-chip used in these applications are often deliberately attacked. This puts the security of our data at a high risk. Furthermore, many SoC devices have become battery-powered and require very low power consumption. In this context, semiconductor manufacturers should propose secured and low-power solutions.This thesis presents a security evaluation and a countermeasures design for a low-power, triple-well architecture dedicated to low-power applications. The security context of this research focuses on a Laser sensitivity evaluation of this architecture.This paper first presents the state of the art of Laser fault injection techniques, focusing on the physical effects induced by a Laser beam. Afterward, we discuss the different dual-and triple-well architectures studied in order to compare their security robustness. Then, a physical study of these architectures as substrate resistor and capacitor modeling highlights their impact on security. This evaluation lets us anticipate the phenomena potentially induced by the Laser inside the biasing well (P-well, N-well) and the MOS transistors.Following the analysis of the physical phenomena resulting from the interaction between the laser and the silicon, electrical modeling of the CMOS gates was developed for dual and triple-well architectures. This enabled us to obtain a good correlation between measurements and electrical simulations.In conclusion, this work enabled us to determine possible design rules for increasing the security robustness of CMOS gates as well as the development of Laser sensors able to detect an attack.

Dans les cancers du sein triple négatif sporadiques, BRCA1 est fréquemment inactivé au niveau transcriptionnel, et il a été rapporté que cette inactivation peut être réalisée par une méthylation du promoteur. Plus récemment, il a été constaté que BRCA1 peut également être régulée au niveau post-transcriptionnel par les microARNs. L'accumulation de preuves indique que les miARNs ont un rôle causal dans la tumorigenèse. Nos travaux se sont axés sur l'étude de l’expression et des fonctions des microARN in vitro, in silico et ex vivo.Basé sur nos résultats de profilage de l'expression, quatre miARN candidats (miR-10b, miR-26a, miR-146a et miR-153) ont été choisis comme étant potentiellement impliqués dans le développement du cancer du sein triple négatif. Des essais d'expression exogènes ont révélé que miR-10b et miR-26a, mais pas miR-146a, peuvent réguler négativement l'expression du gène BRCA1 dans les cellules cancéreuses triple négatif MDA-MB-231 et luminales MCF7, alors que miR-153 pourrait réguler négativement l'expression du gène BRCA1 uniquement dans les cellules MCF7. L'analyse in silico des données de Cancer Genome Atlas (TCGA) a confirmé que miR-146a est significativement plus exprimé dans les tumeurs du sein triple négatif par rapport à d'autres tumeurs (non triple négatif) mammaires. L’étude ex vivo a montré que le niveau élévé d’expression de miR-146a et de miR-26 est associé à l’absence des métastases ganglionnaires dans le cancer du sein triple négatif. Aussi une corrélation entre l’expression de 4 miARNs est révélée permettant l’identification de différentes voies de signalisations impliquées dans le cancer du sein triple negatif.Nos travaux fournissent des preuves de l'implication des miARNs spécifiques comme des biomarqueurs potentiels dans le développement du cancer de sein triple négatif. / In sporadic triple-negative breast cancers BRCA1 is frequently inactivated at the transcriptional level, and it has been reported that this inactivation may be brought about by promoter methylation. More recently, it was found that BRCA1 may also be regulated at the post-transcriptional level by miRNAs. Accumulating evidence indicates that miRNAs have a causal role in tumorigenesis. Our work focused on the study of microRNAs expression and functions in vitro, in silico and ex vivo.Based on our expression profiling results, four candidate miRNAs (miR-10b, miR-26a, miR-146a and miR-153) were selected as being potentially involved in triple-negative breast cancer development. Exogenous expression assays revealed that miR-10b and miR-26a, but not miR-146a, can down-regulate the expression of BRCA1 in both triple-negative MDA-MB-231 and luminal epithelial MCF7 breast cancer-derived cells, whereas miR-153 could down-regulate BRCA1 expression only in MCF7 cells. In silico analysis of The Cancer Genome Atlas (TCGA) data confirmed that miR-146a is significantly higher expressed in triple-negative breast tumors compared to other (non triple-negative) breast tumors. The ex vivo study showed that the high level expression of miR-146a and miR-26 is associated with the absence of lymph node metastasis in triple negative breast cancer. Also a correlation between the expression of the 4 miRNAs was revealed, allowing the identification of different signaling pathways involved in the triple negative breast cancer.Our work provides evidence of the involvement of specific miRNAs as potential biomarkers in breast cancer triple negative development.

Triple A syndrome, formerly known as Allgrove syndrome, is an autosomal recessive disorder characterized clinically by adrenal insufficiency, alacrima, achalasia, and neurological abnormalities. We report a 17-year-old boy presented to the endocrine clinic with delayed puberty and a 4-year’s history of fatigue and muscle weakness. He had achalasia, alacrima, and skin and mucosal hyperpigmentation. Hormonal assessment revealed isolated glucocorticoid deficiency. Clinical diagnosis of triple A syndrome was confirmed by sequencing the entire coding region including exon-intron boundaries of the AAAS gene. Analysis revealed a homozygous novel indel mutation encompassing intron 7 to intron 10 of the gene (g.16166_17813delinsTGAGGCCTGCTG; NG_016775). This is the first report of triple A syndrome in Jordan with a novel indel mutation and presenting with delayed puberty.

Introduction: Triple A syndrome (AAAS) is a rare autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency, autonomic dysfunction, and progressive neurodegeneration. Increased oxidative stress, demonstrated in patients’ fibroblasts in vitro, may be a central disease mechanism. N-acetylcysteine protects renal function in patients with kidney injuries associated with increased oxidative stress and improves viability of AAAS-knockdown adrenal cells in vitro. Patient and Results: A boy diagnosed with AAAS presented with short stature and increased oxidative stress in vivo assessed by increased thiobarbituric acid reactive substances (TBARS), which are markers of lipid peroxidation, and by the susceptibility of LDL to oxidation and the capacity of HDL to prevent it. A homozygous missense germline mutation (c.523G>T, p.Val175Phe) in AAAS was identified. N-acetylcysteine (600 mg orally, twice daily) decreased oxidative stress but did not change the patient’s growth pattern. Conclusions: An increase in oxidative stress is reported for the first time in vivo in an AAAS patient. N-acetylcysteine was capable of decreasing TBARS levels, reducing the susceptibility of LDL to oxidation and improving the antioxidant role of HDL. The longterm effect of antioxidant treatment should be evaluated to determine the real benefit for the prevention of the degenerative process in AAAS.

Syftet med studien är att undersöka vilka faktorer som påverkar konsumenternas val av leveransalternativ och varför dessa blir avgörande i konsumenternas sista milen val. Enligt tidigare forskning är sista milen leveranserna e-handelns minst hållbara del men som samtidigt också har störst potential att förändras till att bli mer hållbar. Något som kan ske genom olika påverkansfaktorer vilket kan få konsumenter att välja hållbart. En mix av kvalitativa metoder används vilken innehåller tre olika delstudier - skrivbordsstudie, semistrukturerade intervjuer och fokusgrupper. Studien genomförs inom e-handelsområdet i Sverige. Resultatet visar att ett antal faktorer blir avgörande för konsumenternas hållbara val i SML, varav kunskap och information ses som den främsta bristen vilken måste förbättras. Resultatet visar även på motstridigheter mellan teori, företag och konsumenter. Studien visar då på att konsumenterna inte besitter den hållbarhetsprioriteringen som teorin påstår. Detsamma gäller för företagen där endast 20 företag av de 100 främsta e-handelsföretagen i Sverige erbjuder ett hållbart leveransalternativ i SML. Det framgår ur studien att det krävs mer, tydligare och lättförståddinformation kring hållbarheten i SML. Däremot behöver denna information kommuniceras före, under och efter konsumentens köp. / The purpose of the study is to examine which factors influence consumers’ choice of delivery alternatives and why these factors become decisive in consumer’ last mile choices. According to previous research, last mile deliveries are the least sustainable part of the e-commerce, but at the same time also have the greatest potential to become more sustainable. That can happen through various influencing factors which can get consumers to make sustainable choices. A mix of qualitative methods is used, which contains three different sub-studies - a desktop study, semi-structured interviews and focus groups. The study is carried out in the e-commerce business area in Sweden. Our findings reveal that a number of factors is decisive for consumers’ sustainable choices in SML, of which knowledge and information is seen as the main factor which must be improved. The findings also show contradictions between the theory, the companies and the consumers. The consumers do not possess the priority of sustainability that the theory claims they have. The same applies to the companies where only 20 companies out of the top 100 in the Swedish e-commerce offer a sustainable delivery alternative in SML. The study shows that more, clearer and information that is easier to understand regarding the sustainability of SML is required. On the contrary, this information needs to be communicated before, during and after the consumer's purchase. This thesis is written in Swedish.