Introduction: Breast cancer is the most frequently diagnosed cancer found in women across the world, with an estimated 2.3 million new cases occurring in 2020. Additionally, over 684,000 deaths annually are attributed to breast cancer across the globe, making it the most common cause of cancer-related death in women. Further, treatment of breast cancer relies heavily on whether or not the cancer cells express estrogen, progesterone, and HER 2 receptors and this expression profile is often related to how quickly the cells grow and spread. In the United States, breast cancer cells that are hormone receptor positive and HER-2 negative make up about 73% of breast cancer cases, and cells that do not express any receptor and are known as triple negative, make up around 12% of cases (American Cancer Society, 2019). With that being said, CT1 and CT3 are novel compounds that have a cytotoxic effect on cell lines representing up to 85% of all breast cancer subtypes in the United States. Methods: The leaves of Chromolaena tacotana that contains the flavonoids CT1 and CT3 were dried and placed in a soxhlet extractor using dichloromethane (CH2Cl2) to extract the chlorophyll. The flavonoids were extracted using a column chromatography eluted with trichloromethane (CHCl3), a 1:1 dilution of CHCl3:methanol and methanol, followed by isolation and purification of the compounds. Human breast cancer cell lines MCF7, MDA-MB-231, and SKBr3 were treated with CT1 and CT3 at concentrations of 5, 10, 20, 40 and 80 µM, followed by incubation for 24 hours. To assess cell viability an MTT assay was conducted by adding a 5-diphenyl-tetrazolium bromide reagent. The purple-colored formazan crystals were solubilized with acidified isopropanol, then analyzed by spectrophotometry. Results: CT1 appeared to have the most cytotoxic effects compared to CT3 on MCF7. The opposite effect was observed for SKBr3 with CT3 showing the most effects as compared to CT1. No differential effect was observed on MDA-MB-231 since both CT1 and CT3 showed similar inhibition of cell viability. Conclusions: The results from the different breast cancer cell lines SKBr3, MCF7, and MDA-MB-231 vary based on how they responded to CT1 and CT3. CT3 was more effective on SKBr3 than CT1. CT1 was more effective on MCF7 than CT3. For MDA-MB-231, both CT1 and CT3 showed similar significant cytotoxic effects. The antiproliferative effects of CT1 and CT3 appear to be concentration dependent on all cells studied. In view of the results from MDA-MB-231 triple negative breast cancer cell line, the cytotoxic effect of the flavonoids is not dependent on the presence of estrogen, progesterone, or HER2 receptors on breast cancer cells. Further studies on the mechanism of action are necessary to elucidate the molecular targets of CT1 and CT3.

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Alkohol och droger har varit ett problem i många år då ungdomar börjar dricka och testa droger redan i ung ålder. Trots att det är en nedåtgående trend där ungdomar dricker mindre alkohol och brukar mindre droger är det viktigt att lyfta fram och belysa detta problem. Denna studie har analyserat serien Störst av allt för att se hur drog- och alkoholanvändning representeras bland ungdomskaraktärerna.    Studien använder sig av representationsteorin vid sidan av metoden multimodal kritisk diskursanalys, MDA. De två frågeställningarna som studien använder för att ta reda på hur serien Störst av allt representerar droger och alkohol hos ungdomskaraktärerna är: “Hur gestaltas drog- och alkoholanvändningen diskursivt och visuellt hos ungdomar i serien Störst av allt?” och “Hur gestaltas dryckesmotiv hos ungdomskaraktärerna?”   Resultatet av studien visade att det fanns flera diskursiva teman som visas visuellt i serien. Det fanns stereotypiska gestaltningar om hur personen som säljer droger ser ut och vart den kommer ifrån, så som att den som säljer droger kommer från förorten och har utländskt påbrå. Ett annat diskursivt tema som serien visade var att ungdomarna oftast konsumerade alkohol i samband med fester medan drogkonsumtionen brukades för att fly från verkligheten. Dessa teman visades genom attribut, scenmiljö, kameravinklar, framträdanden, kroppshållning och blick, lexikala val samt värdeladdade ord. Resultatet av vilka dryckesmotiv ungdomskaraktärerna hade var att Sebastian ofta bara drack alkohol för att fly från sina problem och verkligheten, därav var hans dryckesmotivet hantering. Maja hade dryckesmotiven förbättring och socialisering då hon ofta drack i samband med fest eller för att det var ett socialt sammanhang som middag. Till skillnad från tidigare studier där droger oftast gestaltas som något kul ungdomar gör för nöjes skulle gestaltas drogkonsumtionen i Störst av allt som något mörkt och för att fly verkligheten.

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There is a growing interest in using naturally-occurring compounds as cancer chemopreventive or chemotherapeutic agents. This study investigated the anticancer potential of the graviola fruit extract (GFE) on specific human breast cancer (BC) cells. GFE was found in our preliminary screening to selectively inhibit the growth of certain human BC cells (MDA-MB-468) but did not affect non-transformed breast epithelial MCF-10A cells. GFE treatment was very effective against the growth of MDA-MB-468 BC cells with an IC50 of 4.8 µg/ml. In vitro, effects of GFE treatment on MDA-MB-468 BC cells were further examined for apoptosis and cell proliferation. Apoptosis, determined qualitatively and quantitatively, was enhanced and accompanied by caspase-3 activation. GFE treatment also induced cell cycle arrest at the G1 cell cycle phase and significantly reduced the percentage of MDA-MB-468 cells in S-phase following 24h of exposure. Moreover, the results from analysis of the mRNA expression of epidermal growth factor receptor (EGFR), which plays an important role in regulating cell development and death, by qRT-PCR, suggested that GFE-induced selective growth inhibition of MDA-MB-468 BC cells is associated with a significant inhibition of EGFR gene expression in the cells. In vivo, dietary treatment with GFE significantly inhibited MDA-MB-468 tumor growth implanted in mice by reducing tumor wet weight and significantly reduced EGFR and p-ERK protein expression in tumors. Overall, GFE attenuated cell proliferation, induced apoptosis, modulated cell cycle regulation and downregulated EGFR gene expression both in vitro and in vivo. These discoveries support the further studies to fully elucidate the antitumor potential of GFE and its components as a dietary agent for BC. / Master of Science in Life Sciences

Syftet med studien är att undersöka hur fyra utbildade och verksamma mellanstadielärare undervisar i läsförmåga. Studien undersöker därmed dessa tre forskningsfrågor: Hur pratar lärare om begreppet läsförmåga? Hur undervisar lärare i läsförmåga? Vilka resurser använder lärare i deras undervisning? Genom att använda oss av kvalitativa metoder samlade vi in data genom en kombination av tre metoder. Dessa metoder utgörs av intervjuer, observationer och insamling av lärarnas lektionsplaneringar. Tidigare forskning visar att elever behöver få rätt strategier med sig för att kunna tolka texter där både läsförståelse och ordkunskaper bör löpa parallellt i undervisningen för att ge eleverna de bästa möjligheterna till att utveckla sin läsförmåga. Resultatet i vår studie visar hur lärare med en stor erfarenhet inom yrket genomför undervisning om läsförmåga. Samtliga lärare benämner att läsförmåga innebär läsförståelse och ordkunskap. Dessa områden visar sig ta större fokus av lärarnas undervisning. Lärarna planerar sin undervisning i läsförmåga utefter deras erfarenhet om vilket tillvägagångsätt som de anser är bäst. Resultatet visar att lärarna anpassar sin undervisning efter elevgrupper och genomför en tydlig pedagogisk och professionell undervisning.

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O crescimento do mercado de alimentos funcionais e orgânicos, assim como a maior conscientização do consumidor em relação aos efeitos tóxicos e mutagênicos de alguns aditivos artificiais, tem impulsionado a indústria a substituir compostos artificiais por naturais. Emulsões alimentícias, como salsichas e maionese, são sistemas bifásicos altamente suscetíveis às reações de oxidação lipídica responsável pela degradação da coloração dos produtos e formação de off-flavors desagradáveis. Para retardar ou inibir a oxidação e aumentar o sheff fife das emulsões, a indústria alimentícia faz uso de compostos sintéticos artificiais. Desta forma, o objetivo deste estudo foi de, inicialmente, avaliar a atividade antioxidante de vinte e dois compostos (artificiais e naturais), classificando-os de acordo com a atividade antioxidante determinada através de cinco diferentes metodologias in vitro. As amostras foram classificadas em três clusters de acordo com os resultados expressos como equivalentes de trolox (TE) observados nos diferentes métodos. A aplicação das técnicas estatísticas multivariadas sugeriu que dentre os compostos que apresentaram maior atividade antioxidante, a partir dos métodos DPPH, FRAP, TBARS e ORAC, foram ácido cafeico, ácido carnósico, genisteína e resveratrol. Essa propriedade apresentou correlação significativa com o número de anéis fenólicos e estrutura catecólica presentes nessas moléculas. Baseando-se nessa classificação, e na hipótese de interações positivas para a resposta antioxidante foram selecionados três compostos hidrossolúveis (ácido cafeico, ácido carnósico e glutationa) e três lipossolúveis (quercetina, rutina e genisteína) para composição de duas misturas. A proporção de cada composto foi otimizada a partir da metodologia de superfície de resposta (MSR) avaliando-se a atividade antioxidante por três metodologias in vitro. A otimização do modelo polinomial sugeriu que as misturas contendo 47% de ácido cafeico e 53% de ácido carnósico ou 67% de quercetina e 33% de rutina apresentaram sinergismo, tornando essas combinações potencialmente interessantes para futura aplicação em matrizes alimentícias. A efetividade antioxidante das misturas otimizadas em relação a um composto artificial foi avaliada em uma emulsão alimentícia (salsicha) na proporção 5OO e 800 mg/Kg. Ambas misturas (hidro e lipossolúveis) em ambas dosagens apresentaram menores concentrações de TBARS que a amostra formulada com o eritorbato de sódio durante o sheff fife. Considerando-se o resultado da análise sensorial como critério de viabilidade, a mistura quercetina + rutina (5OO mg/Kg), apresentou-se como melhor alternativa de substituição do eritorbato de sódio na formulação de salsichas tipo hot dog. / The growth of the functional and organic food market combined with customer awareness about the toxicological and mutagenic effects observed in some artificial additives have stimulated the companies to replace artificial with natural compounds in the food formulation. Emulsions are biphasic systems that are highly susceptible to Iipid oxidation which is able to cause damage to the color of products and the formation of undesirable bad flavors. In order to retard or inhibit the oxidation and extend the emulsions shelf-life companies have applied synthetic artificial compounds. Therefore, the objective of this study was to evaluate the antioxidant activity of twenty two compounds (artificial and natural) and classify them according to their antioxidant activity as measured by tive different in vitro methodologies. The samples were classified into three clusters in function of their antioxidant activity expressed as Trolox equivalents (TE). The application of multivariate statistical techniques suggested that caffeic acid, carnosic acid, genistein and resveratrol showed greater antioxidant activity when evaluated by DPPH, FRAP, TBARS and ORAC methodologies. The antioxidant activity of these compounds showed a significant positive correlation with the number of phenolic rings and cathecol structures present in these molecules. Three hydrosolube compounds (caffeic acid, carnosic acid and gluthatione) and three liposoluble compounds (quercetin, rutin and genistein) were selected to prepare two assays based on the multivariate classification and on the hypothesis of positive interactions to the antioxidant response. The proportion of each compound in the mixture was optimized by the response surface methodology (RSM) on the results obtained from three in vitro methodologies. The optimization of the polynomial models suggested that mixtures containing 47% caffeic acid and 53% carnosic acid, or 67% quercetin and 33% rutin showed synergism making these mixtures potentially viable solutions for applications in the food matrix. The antioxidant effectiveness of the optimized mixtures compared to an artificial compound was evaluated in the food emulsion (sausages) in two dosages (500 and 800 mg/Kg). Both mixtures (hydrosoluble and liposoluble) in both dosages, promoted lower TBARS concentration than the sample formulated with sodium erythorbate during a shelf-life of 45 days under refrigeration. However, using into sensory results as selection criteria, the mixture containing quercetin and rutin at dosage of 500 mg/kg, proved to be the best alternative to replace sodium erythorbate in the sausage formulations.

Software development is a complex task. Executable applications comprise a mutlitude of diverse components that are developed with various frameworks, libraries, or communication platforms. The technical complexity in development retains resources, hampers efficient problem solving, and thus increases the overall cost of software production. Another significant challenge in market-driven software engineering is the variety of customer needs. It necessitates a maximum of flexibility in software implementations to facilitate the deployment of different products that are based on one single core. To reduce technical complexity, the paradigm of Model-Driven Software Development (MDSD) facilitates the abstract specification of software based on modeling languages. Corresponding models are used to generate actual programming code without the need for creating manually written, error-prone assets. Modeling languages that are tailored towards a particular domain are called domain-specific languages (DSLs). Domain-specific modeling (DSM) approximates technical solutions with intentional problems and fosters the unfolding of specialized expertise. To cope with feature diversity in applications, the Software Product Line Engineering (SPLE) community provides means for the management of variability in software products, such as feature models and appropriate tools for mapping features to implementation assets. Model-driven development, domain-specific modeling, and the dedicated management of variability in SPLE are vital for the success of software enterprises. Yet, these paradigms exist in isolation and need to be integrated in order to exhaust the advantages of every single approach. In this thesis, we propose a way to do so. We introduce the paradigm of Multi-Domain Engineering (MDE) which means model-driven development with multiple domain-specific languages in variability-intensive scenarios. MDE strongly emphasize the advantages of MDSD with multiple DSLs as a neccessity for efficiency in software development and treats the paradigm of SPLE as indispensable means to achieve a maximum degree of reuse and flexibility. We present HybridMDSD as our solution approach to implement the MDE paradigm. The core idea of HybidMDSD is to capture the semantics of particular DSLs based on properly defined semantics for software models contained in a central upper ontology. Then, the resulting semantic foundation can be used to establish references between arbitrary domain-specific models (DSMs) and sophisticated instance level reasoning ensures integrity and allows to handle partiucular change adaptation scenarios. Moreover, we present an approach to automatically generate composition code that integrates generated assets from separate DSLs. All necessary development tasks are arranged in a comprehensive development process. Finally, we validate the introduced approach with a profound prototypical implementation and an industrial-scale case study. / Softwareentwicklung ist komplex: ausführbare Anwendungen beinhalten und vereinen eine Vielzahl an Komponenten, die mit unterschiedlichen Frameworks, Bibliotheken oder Kommunikationsplattformen entwickelt werden. Die technische Komplexität in der Entwicklung bindet Ressourcen, verhindert effiziente Problemlösung und führt zu insgesamt hohen Kosten bei der Produktion von Software. Zusätzliche Herausforderungen entstehen durch die Vielfalt und Unterschiedlichkeit an Kundenwünschen, die der Entwicklung ein hohes Maß an Flexibilität in Software-Implementierungen abverlangen und die Auslieferung verschiedener Produkte auf Grundlage einer Basis-Implementierung nötig machen. Zur Reduktion der technischen Komplexität bietet sich das Paradigma der modellgetriebenen Softwareentwicklung (MDSD) an. Software-Spezifikationen in Form abstrakter Modelle werden hier verwendet um Programmcode zu generieren, was die fehleranfällige, manuelle Programmierung ähnlicher Komponenten überflüssig macht. Modellierungssprachen, die auf eine bestimmte Problemdomäne zugeschnitten sind, nennt man domänenspezifische Sprachen (DSLs). Domänenspezifische Modellierung (DSM) vereint technische Lösungen mit intentionalen Problemen und ermöglicht die Entfaltung spezialisierter Expertise. Um der Funktionsvielfalt in Software Herr zu werden, bietet der Forschungszweig der Softwareproduktlinienentwicklung (SPLE) verschiedene Mittel zur Verwaltung von Variabilität in Software-Produkten an. Hierzu zählen Feature-Modelle sowie passende Werkzeuge, um Features auf Implementierungsbestandteile abzubilden. Modellgetriebene Entwicklung, domänenspezifische Modellierung und eine spezielle Handhabung von Variabilität in Softwareproduktlinien sind von entscheidender Bedeutung für den Erfolg von Softwarefirmen. Zur Zeit bestehen diese Paradigmen losgelöst voneinander und müssen integriert werden, damit die Vorteile jedes einzelnen für die Gesamtheit der Softwareentwicklung entfaltet werden können. In dieser Arbeit wird ein Ansatz vorgestellt, der dies ermöglicht. Es wird das Multi-Domain Engineering Paradigma (MDE) eingeführt, welches die modellgetriebene Softwareentwicklung mit mehreren domänenspezifischen Sprachen in variabilitätszentrierten Szenarien beschreibt. MDE stellt die Vorteile modellgetriebener Entwicklung mit mehreren DSLs als eine Notwendigkeit für Effizienz in der Entwicklung heraus und betrachtet das SPLE-Paradigma als unabdingbares Mittel um ein Maximum an Wiederverwendbarkeit und Flexibilität zu erzielen. In der Arbeit wird ein Ansatz zur Implementierung des MDE-Paradigmas, mit dem Namen HybridMDSD, vorgestellt.

No description available.