Characterization and modeling of devices at high drive levels often requires specialized equipment and measurement techniques. Many large-signal devices will never have traditional nonlinear models because model development is expensive and time-consuming. Due to the complexity of the device or the size of the application market, nonlinear modeling efforts may not be cost effective. Scattering parameters, widely used for small-signal passive and active device characterization, have received only cursory consideration for large-signal nonlinear device characterization due to technical and theoretical issues. We review the theory of S-parameters, active device characterization, and previous efforts to use S-parameters with large-signal nonlinear devices. A robust, calibrated vector-measurement system is used to obtain device scattering parameters as a function of drive level. The unique measurement system architecture allows meaningful scattering parameter measurements of large-signal nonlinear devices, overcoming limitations reported by previous researchers. A three-port S-parameter device model, with a nonlinear reflection coefficient terminating the third port, can be extracted from scattering parameters measured as a function of drive level. This three-port model provides excellent agreement with device measurements across a wide range of drive conditions. The model is used to simulate load-pull data for various drive levels which are compared to measured data. / Master of Science

Ce document a pour but de présenter la prévision de l’inflation à l’aide du modèle ARIMA et la Courbe de Phillips. Il est important de s’intéresser à ce sujet en tant qu’économiste, car c’est une variable macroéconomique essentielle qui influence les choix économiques et financiers. Plusieurs méthodes existent pour prévoir l’inflation dont le modèle ARIMA et la courbe de Phillips. Le modèle ARIMA est très robuste en ce sens qu’il englobe le processus autorégressif, la partie de différenciation et la composante de moyenne mobile. Cependant, la courbe de Phillips standard met en évidence la relation inverse entre l’inflation et le taux de chômage. Par ailleurs, la courbe de Phillips améliorée établit la relation inverse entre l’inflation et le taux de chômage et la relation positive entre l’inflation et le taux de de change et le taux d’intérêt de court terme. La méthode employée pour obtenir le modèle ARIMA est l’approche de Box-Jenkins. De plus, le meilleur modèle ARIMA obtenu de la série de l’inflation canadienne est ARIMA (3,1,2) pour les données mensuelles de l’inflation de 1971 à 2016. Le meilleur modèle observé est la courbe de Phillips améliorée. Cela est d’autant plus normale, car le Canada est une petite économie ouverte, et donc ces variables macroéconomiques dépendent en partie de la situation économique de l’extérieur. Néanmoins, la courbe de Phillips améliorée révèle que le taux de chômage influence en majeure partie le taux d’inflation. Nos résultats présentent des prévisions à la baisse du niveau d’inflation de 2017 à 2020, ce qui est conforme avec l’évolution des valeurs réalisées de l’inflation canadienne.

This report describes the process of developing a new package for food-related liquids. The assignment is done on behalf of the design and branding agency Motherland and is a Bachelor of Science degree in Innovation and Design at Karlstad University. The client wants to find a new design for packaging where the end product is similar to the Bag-in- box concept. The Bag-in-box concept is good in many ways, with its block-shaped design almost pallet optimised, it has a simple construction, less environmental impact than glass, aluminum and PET bottles and less expensive to produce. In spite of its popularity in Sweden and well as the rest of the world, the pre-study shows that there are many users who think that the concept has its flaws. Common users claim the package does not reflect the contents and is difficult to empty and disassemble. The package can only be used standing at the edge of the table. The goal of this product development project is to apply the designprocess to find one or more prototypes with new design which meets the demands of the consumers. The project is limited to finding a new solution on the outer packaging and do not take into account the dosing function. The product must be suited for storage and transport to meet the requirements of sustainable development. The feasibility study gave insight and knowledge of the output concept, the facts surrounding a number of food related liquids, information about effective tools for idea development, sustainable development and the approach to manufacture an environmentally friendly packaging. Facts gathered through literature studies, study, survey, form studies, component analysis and visits knowledgeable in relevant areas. The study resulted in a specification that was used as a guide in the product development process. The project resulted in two prototypes with the same engineering design and volume but with different dimensions on height and width. They have a new design and a new mindset when it comes drain but have the same final function as the starting product, to protect the fluid, contain fluid, moving liquids, and dosing liquid. They have an opening and resealable lid that allows the user to control the content and facilitates proper recycling. It enables the packaging to be easily taken out and thus simplify the emptying of all content. Sketching and modeling has been of great help in the work and its results. / Denna rapport beskriver ett examensarbete där två prototyper på ytterförpackning för livsmedelsrelaterade vätskor är slutresultatet. Uppdraget sker i samarbete med design- och varumärkesbyrån Motherland och är ett examensarbete på högskoleingenjörsprogrammet i innovationsteknik och design på Karlstads universitet. Uppdragsgivaren vill ta fram en ny design på förpackning för vätskor där utgångsprodukten är Bag-in-box konceptet. Utgångsprodukten är bra i många avseenden, den är med sin blockformade konstruktion nästintill logistisk optimal för transport och lagring, har en enkel konstruktion, ger mindre negativ miljöpåverkan än både glas-, aluminium- och PET-flaskor och är billig att producera. Trots sin popularitet i så väl Sverige som övriga världen, visar förstudien att det är många brukare som anser att utgångsprodukten har sina brister. Många anser att förpackningen inte är tilltalande designmässigt, det är svårt att tömma på allt innehåll och att det är komplicerat då produkten skall elimineras. Att det endast doseras vid en bordskant är en annan nackdel. Målet med projektet är att med utgångspunkt i designprocessen gestalta och ge förslag på en eller flera prototyper på ytterförpackning där ny form och design står i fokus. Produkten måste vara lager och transportanpassad så att den tillgodoser krav på hållbar utveckling. Hänsyn skall tas till användarnas krav så att den/de nya produkterna tillgodoser brister hos utgångsprodukten. Förstudien gav insikt och kunskap om utgångskonceptet, fakta kring ett antal livsmedelsrelaterade vätskor, information om effektiva verktyg för idéutveckling, hållbar utveckling och tillvägagångssätt för tillverkning av en miljöanpassad förpackning. Fakta samlades in genom litteraturstudier, studiebesök, enkätundersökning, formstudier, komponentanalys och besök hos kunniga på relevanta områden. Förstudien resulterade i en kravspecifikation som användes som vägledning i produktutvecklingensprocessen. Projektet resulterade i två prototyper med samma konstruktionsdesign och volym men med olika dimensioner på höjd och bredd. De har en ny design och ett nytt tänk när det gäller utpumpningsfunktion dock har den samma slutfunktion som utgångsprodukten, skydda vätska, innehålla vätska, förflytta vätska och dosera vätska. De har ett öppnings- och återförslutningsbart lock som möjliggör för brukaren att kontrollera innehållet och underlättar för rätt källsortering. Lösningen gör att innerförpackningen lätt kan tas ur och på så sätt förenkla vid tömning av allt innehåll. Skissande och modellering har varit till stor hjälp i arbetet och framtagandet av slutresultatet.

Le riz (Oryza sativa L) est la source principale d'alimentation pour plus de la moitié de la population mondiale (Khush, 2005). La production de riz devrait augmenter de plus de 40% en 2030 pour satisfaire la demande de croissance de la population. Chaque année, environ 25% de la production est perdue à cause des insectes ravageurs, des maladies et des mauvaises herbes (Khus, 2005). Des pertes semblables sont dues aux stress abiotiques comme la sécheresse. L'objectif de mon travail de thèse a consisté à étudier la fonction de deux facteurs de transcription (FT) à boîte MADS OsMADS25 et OsMADS26 dans la réponse aux stress ou dans le développement. Pour cela, j'ai généré des lignées de riz surexprimant les ADNc codant ces FT et aussi des lignées interférées pour le gène OsMADS26 en utilisant deux GST différentes pour induire de l'ARN interférence destiné à détruire les ARNm OsMADS26. Dans le cas du gène OsMADS25 qui appartient à un groupe de cinq gènes phylogénétiquement proches, j'ai généré des plantes exprimant la protéine OsMADS25 fusionnée avec le motif répresseur dominant de la transcription EAR. Les lignées T2 exprimant le FT OsMADS25 fusionné au motif EAR présentent un phénotype semblable à celui d'une lignée d'insertion de TDNA dans ce gène. Ces plantes sont caractérisées par une forte réduction du nombre de leur talle et par une hauteur plus importante de la talle principale. Les plantes qui surexpriment OsMADS25 natif ne présentent pas de phénotype particulier. Ceci suggère que le gène OsMADS25 pourrait être impliqué dans la régulation du nombre de talles chez le riz bien qu'il soit exprimé au niveau de la racine. Le mode d'action du gène OsMADS25 sur le contrôle du développement des méristèmes axillaire du riz reste à préciser. Les lignées interférées OsMADS26 présentent une meilleure résistance à Magnaporthe oryzae (Mo) et à Xanthomonas oryzae pv. Oryzae (Xoo), deux principaux pathogènes du riz, et aussi une meilleure capacité de restauration après l'application d'un stress hydrique par rapport aux lignées témoin tandis que les lignées surexprimant OsMADS26 sont plus sensibles à ces stress. Les analyses de QPCR et du transcriptome que nous avons effectuées ont mis en évidence l'expression constitutive plus élevée dans les lignées interférées de plusieurs gènes de réponse aux stress biotique et abiotique. Ces résultats suggèrent que OsMADS26 pourrait être un inhibiteur général des mécanismes de défense de la plante et que les plantes interférée OsMADS26 sont dans un statut physiologique de type primed-like qui leur permettent d'être plus résistantes aux stress. Les lignées interférées pour OsMADS26 sont très peu affectées dans leur développement. Le gène OsMADS26 est donc un gène très intéressant pour les programmes d'amélioration du riz / MADS-box transcription factors (TF) have been mostly characterized for their involvement of plant development such as floral organogenesis and flowering time. Some of them are involved in stress related developmental processes such as abscission, fruit ripening and senescence. Overexpression of the rice OsMADS26 TF suggested a function in stress response. Here we report that OsMADS26 interfered lines presented a better resistance against two major pathogens of rice, Xanthomonas oryzae (Xoo) and Magnaportae oryzae (Mo) and a better recovery capacity after a water stress period. Transcriptome analysis revealed that several biotic and abiotic stresses related genes were up regulated in OsMADS26 interfered lines. In addition QPCR analysis showed that the expression of a set of biotic and abiotic genes was induced when OsMADS26 interfered lines were infected by Xoo or submitted to a water stress. This indicated that OsMADS26 is a negative regulator of biotic and abiotic stress response in rice. Taking in account the data previously published that showed that inducible overexpression of OsMADS26 resulted in the activation of expression of genes involved in jasmonic acid or reactive oxygen species biosynthesis, we postulate that OsMADS26 may be a hub regulator of stress response in rice and that it may be posttranscriptional regulated to modulate negatively or positively rice response to various stresses.In addition we have shown in this thesis that an insertion mutant line disrupting the OsMADS25 gene is characterized by a reduced number of tiller. This phenotype was also obtained in transgenic lines expressing the OsMADS25 transcription factor fused with a dominant motif inhibitor of transcription. Thissuggested that OsMADS25 is involved in the control of tiller development in rice.Key words: Rice, stress, blast, tillering, MADS-box, transcription factor, OsMADS26, OsMADS25, transcriptome

La tomate (Solanum lycopersicum) est l’espèce modèle pour l’étude des fruits charnus. Le développement du fruit de tomate a été décrit comme une succession de phases de développement distinctes, dans lesquelles les régulations hormonales jouent un rôle crucial. Afin de mieux comprendre la régulation du développement du fruit de tomate, des approches ciblées sur des catégories particulières de protéines régulatrices (F-Box) ainsi que des approches non ciblées de génomique fonctionnelle ont été menées dans le laboratoire. L'objectif de cette thèse est de contribuer à la validation fonctionnelle de gènes candidats mis en évidence dans ces travaux: trois protéines à F-Box (SlFB2, SlFB11 et SlFB24) et deux facteurs de transcription (SlHAT22 et SlTGA2.1). Au cours de cette thèse, la caractérisation de lignées RNAi précédemment générés pour les protéines SlFB2, SlFB11 et SlFB24 a été poursuivie. Ce travail n’a pas permis pas de conclure sur le rôle de ces protéines à F-Box dans le développement du fruit de tomate. Mais elle a permis d'isoler un mutant d'insertion dans une lignée RNAi SlFB2, spécifiquement affecté au niveau des fruits. Ce mutant est caractérisé par l'absence de développement de tissu loculaire, ce qui entraine une altération de la forme des graines, ainsi qu'une augmentation de la fermeté du fruit. Le site d'insertion de l'ADN-T dans ce mutant n'est pas encore identifié. En outre, la caractérisation des lignées RNAi SlFB11, a permis de proposer l'implication de cette protéine dans la régulation des méristèmes apicaux et floraux. La caractérisation fonctionnelle de SlHAT22 et SlTGA2.1 a été initiée par la génération de lignées transgéniques présentant une altération du niveau d'expression de ces facteurs de transcription (sur-expression et RNAi) ou une altération de la fonction du facteur de transcription par utilisation de la technologie CRES-T. La caractérisation phénotypique des lignées transgéniques, ainsi que des analyses métaboliques préliminaires ont révélé que SlTGA2.1 et SlHAT22 sont impliqués dans des processus de régulation au cours du développement précoce du fruit de tomate. En outre, ils ont également suggéré que SlTGA2.1 est impliqué dans la régulation du murissement du fruit de tomate. / Tomato (Solanum lycopersicum) is a model species for the study of fleshy fruits. Tomato fruit development has been described as a sequence of distinct developmental phases where different hormones play crucial regulatory roles. To further gain insight into the regulation of tomato fruit development, targeted approaches focused on particular classes of regulatory proteins (F-Box) as well as global functional genomics approaches were undertaken in the laboratory. The aim of this thesis was to contribute to the functional validation of candidate genes isolated from such approaches: three F-Box proteins (SlFB2, SlFB11 and SlFB24) and two transcription factors (SlHAT22 and SlTGA2.1).During this PhD thesis, the characterization of SlFB2, SlFB11 and SlFB24 RNAi lines previously generated was pursued. This work does not allow to conclude about the role of these F-Box in tomato fruit development. But it allowed to isolate an insertion mutant in a SlFB2 RNAi line, specifically affected at the fruit level. This mutant is characterized by the absence of locular tissue development and subsequent alteration of seed shape, as well as by an increase in fruit firmness. The insertion site of the T-DNA in this mutant is not yet identified. In addition, characterization of SlFB11 RNAi lines, allowed to propose the implication of this protein in the regulation of the shoot apical and floral meristems.Functional characterization of SlHAT22 and SlTGA2.1 was initiated by the generation of transgenic lines carrying an alteration of the transcription factor (TF) expression level (OE and RNAi lines) or with an alteration of TFs function using the CRES-T technology. Phenotypical characterization of the transgenic lines, together with preliminary metabolic analyses revealed that SlTGA2.1 and SlHAT22 are implicated in regulatory processes during tomato early fruit development. In addition, they also suggested that SlTGA2.1 is involved in the regulation of tomato fruit ripening.

Os tumores de musculatura liso do útero se desenvolvem a partir do miométrio e podem apresentar carcterísticas clínicas malignas e benignas. Dentre eles, o leiomiossarcoma (LMS) é o tumor maligno mais comum, com altas taxas de metástase e recidiva, mesmo sendo diagnosticado em estágios iniciais. Já os leiomiomas (LM) são os tumores benignos mais frequentes em mulheres em idade reprodutiva. Ambos possuem mesma diferenciação celular, porém com comportamentos clínico e biológico bastante distintos, e até o momento não se dispõe de tratamento específico ou curativo. Nesse contexto, a busca por novos alvos moleculares pode contribuir não só para um melhor entendimento dessas neoplasias, como também para a descoberta de novas terapias. Em estudo prévio foi observada a expressão aumentada de FOXO3a nos sarcomas uterinos, em comparação aos LMs e ao miométrio adjacente (MM). Além disso, sua expressão foi crescente de acordo com o potencial de malignidade do tumor. Assim, o objetivo do presente estudo foi avaliar in vitro o efeito de terapia alvo específica para FOXO3a em células de LM e LMS. Para isto, linhagens celulares de MM (ATCC PCS-460-011), LM (THESCs - CRL-4003) e LMS (SK-UT-1 - HTB-114) foram caracterizadas quanto à expressão basal de FOXO3a (gene e proteína) e submetidas a tratamento com Genisteína e Metformina ou inativação do gene por siRNA. Os efeitos dos tratamentos foram avaliados por PCR em tempo real, Western Blot, imunocitoquímica, ensaios de proliferação, migração e apoptose. Nossos resultados mostraram que todos os tratamentos realizados interferiram na capacidade de proliferação e migração das células, com maior inibição após as 48 horas nos LMS e 72h nos LM. O efeito obtido na transfecção com siRNA apresentou maior eficiência após 48 h da transfecção nos LMS e 72h nos LM. Os efeitos da inibição de FOXO3a foram maiores na proliferação e migração dos LM, porém os resultados não foram estatisticamente significativos. Dentre as substâncias testadas, a Metformina apresentou maior efeito sobre a proliferação, migração e viabilidade das linhagens celulares. A Genisteína também apresentou efeito inibitório nas células, porém o controle com veículo também apresentou o mesmo efeito citotóxico. De modo geral, os efeitos obtidos com os fármacos, foram tempo e concentração dependentes. Em conjunto, nossos resultados sugerem um relevante do FOXO3a nos tumores de musculatura lisa uterinos, além de apresentá-lo como potencial alvo para terapia específica / Smooth muscle tumors of the uterus develop from the myometrium and may present benign and malignant clinical features. Among them, leiomyosarcoma (LMS) is the most frequent malignant tumor, with high rates of metastasis and relapse, even when diagnosed in early stages. On the other hand, leiomyomas (LM) are the most frequent benign tumors in women of reproductive age. Both have the same cellular differentiation, but with very different clinical and biological behaviors, and so far no specific or curative treatment is available. In this context, the search for new molecular targets can contribute not only for a better understanding of these neoplasms, but also for the discovery of new therapies. In a previous study, increased expression of FOXO3a in uterine sarcomas was observed, compared to LMs and adjacent myometrium (MM). In addition, its expression was increasing according to the malignancy potential of the tumor. Thus, the aim of the present study was to evaluate in vitro, the effect of specific targeted therapy for FOXO3a on LM and LMS cells. For this, MM (ATCC PCS-460-011), LM (THESCs-CRL-4003) and LMS (SK-UT-1-HTB-114) cell lines were characterized for basal expression of FOXO3a (gene and protein) and subsequently submitted to treatment with metformin and genistein, or silencing of FOXO3a by siRNA. The effects of the treatments were evaluated by real-time PCR, Western Blot, immunocytochemistry, proliferation, migration and apoptosis assays. Our results showed that all treatments interfered in the proliferation and migration capacity of the cells, with greater inhibition after 48 hours for LMS and 72 hours LM. The effect obtained in the transfection with siRNA showed higher efficiency after 48 hours of transfection in LMS and 72 hours in LM. The effects of inhibition of FOXO3a were greater in the proliferation and migration of the LM, but the results were not statistically significant. Among the substances tested, Metformin had a greater effect on proliferation, migration and viability of the cell lines. Genistein also had an inhibitory effect on the cells, but the control with the vehicle also presented the same cytotoxic effect. In general, the effects obtained with the drugs were time and concentration dependent. Together, our results suggest a relevant role of FOXO3a in uterine smooth muscle tumors, in addition to presenting it as a potential target for specific therapy

As RNA helicases da família DEAD-box são enzimas que alteram as estruturas secundárias do RNA e auxiliam a formação de complexos ribonucleoproteicos, e são muito importantes em processos basais como a degradação dos RNAs e a biogênese dos ribossomos. A α-proteobactéria criotolerante Caulobacter crescentus é um modelo experimental interessante para compreender o papel destas enzimas em baixa temperatura. A caracterização fenotípica de linhagens mutantes simples de quatro RNA helicases DEAD-box permitiu demonstrar que a RNA helicase RhlE é necessária para o crescimento em baixa temperatura. Os mutantes duplos mostraram redução do crescimento à temperatura normal e em baixa temperatura, com perda de viabilidade e alterações morfológicas. Através de ensaios de complementação cruzada mostrou-se que seus papéis fisiológicos são até certo ponto redundantes. O mutante rhlE também apresentou redução na formação de biofilme. A medida da expressão relativa dos genes que codificam as RNA helicases mostrou um aumento na expressão de três destes genes em estresse frio, e a análise dos perfis ribossomais mostrou a possível participação destas três RNA helicases na biogênese do ribossomo. / The RNA helicases of the DEAD-box family are enzymes that modify RNA secondary structures and help the formation of ribonucleoprotein complexes, and are very important in basal processes such as RNA degradation and ribosome biogenesis. The cryotolerant α-proteobacterium Caulobacter crescentus is an interesting experimental model to understand the role of these enzymes at low temperature. The phenotypic characterization of strains with single mutations of four DEAD-box RNA helicases showed that RNA helicase RhlE is required for growth at low temperature. The double mutants showed reduction in growth at both normal and low temperatures, with loss of viability and morphological changes. Through cross-complementation assays it has been shown that their physiological roles are to some extent redundant. The rhlE mutant also showed reduction in biofilm formation. The relative expression of the genes encoding the RNA helicases showed an increase in the expression of three of these genes under cold stress, and the analysis of the ribosomal profiles showed the possible participation of these three RNA helicases in ribosome biogenesis.

Os tumores de musculatura liso do útero se desenvolvem a partir do miométrio e podem apresentar carcterísticas clínicas malignas e benignas. Dentre eles, o leiomiossarcoma (LMS) é o tumor maligno mais comum, com altas taxas de metástase e recidiva, mesmo sendo diagnosticado em estágios iniciais. Já os leiomiomas (LM) são os tumores benignos mais frequentes em mulheres em idade reprodutiva. Ambos possuem mesma diferenciação celular, porém com comportamentos clínico e biológico bastante distintos, e até o momento não se dispõe de tratamento específico ou curativo. Nesse contexto, a busca por novos alvos moleculares pode contribuir não só para um melhor entendimento dessas neoplasias, como também para a descoberta de novas terapias. Em estudo prévio foi observada a expressão aumentada de FOXO3a nos sarcomas uterinos, em comparação aos LMs e ao miométrio adjacente (MM). Além disso, sua expressão foi crescente de acordo com o potencial de malignidade do tumor. Assim, o objetivo do presente estudo foi avaliar in vitro o efeito de terapia alvo específica para FOXO3a em células de LM e LMS. Para isto, linhagens celulares de MM (ATCC PCS-460-011), LM (THESCs - CRL-4003) e LMS (SK-UT-1 - HTB-114) foram caracterizadas quanto à expressão basal de FOXO3a (gene e proteína) e submetidas a tratamento com Genisteína e Metformina ou inativação do gene por siRNA. Os efeitos dos tratamentos foram avaliados por PCR em tempo real, Western Blot, imunocitoquímica, ensaios de proliferação, migração e apoptose. Nossos resultados mostraram que todos os tratamentos realizados interferiram na capacidade de proliferação e migração das células, com maior inibição após as 48 horas nos LMS e 72h nos LM. O efeito obtido na transfecção com siRNA apresentou maior eficiência após 48 h da transfecção nos LMS e 72h nos LM. Os efeitos da inibição de FOXO3a foram maiores na proliferação e migração dos LM, porém os resultados não foram estatisticamente significativos. Dentre as substâncias testadas, a Metformina apresentou maior efeito sobre a proliferação, migração e viabilidade das linhagens celulares. A Genisteína também apresentou efeito inibitório nas células, porém o controle com veículo também apresentou o mesmo efeito citotóxico. De modo geral, os efeitos obtidos com os fármacos, foram tempo e concentração dependentes. Em conjunto, nossos resultados sugerem um relevante do FOXO3a nos tumores de musculatura lisa uterinos, além de apresentá-lo como potencial alvo para terapia específica / Smooth muscle tumors of the uterus develop from the myometrium and may present benign and malignant clinical features. Among them, leiomyosarcoma (LMS) is the most frequent malignant tumor, with high rates of metastasis and relapse, even when diagnosed in early stages. On the other hand, leiomyomas (LM) are the most frequent benign tumors in women of reproductive age. Both have the same cellular differentiation, but with very different clinical and biological behaviors, and so far no specific or curative treatment is available. In this context, the search for new molecular targets can contribute not only for a better understanding of these neoplasms, but also for the discovery of new therapies. In a previous study, increased expression of FOXO3a in uterine sarcomas was observed, compared to LMs and adjacent myometrium (MM). In addition, its expression was increasing according to the malignancy potential of the tumor. Thus, the aim of the present study was to evaluate in vitro, the effect of specific targeted therapy for FOXO3a on LM and LMS cells. For this, MM (ATCC PCS-460-011), LM (THESCs-CRL-4003) and LMS (SK-UT-1-HTB-114) cell lines were characterized for basal expression of FOXO3a (gene and protein) and subsequently submitted to treatment with metformin and genistein, or silencing of FOXO3a by siRNA. The effects of the treatments were evaluated by real-time PCR, Western Blot, immunocytochemistry, proliferation, migration and apoptosis assays. Our results showed that all treatments interfered in the proliferation and migration capacity of the cells, with greater inhibition after 48 hours for LMS and 72 hours LM. The effect obtained in the transfection with siRNA showed higher efficiency after 48 hours of transfection in LMS and 72 hours in LM. The effects of inhibition of FOXO3a were greater in the proliferation and migration of the LM, but the results were not statistically significant. Among the substances tested, Metformin had a greater effect on proliferation, migration and viability of the cell lines. Genistein also had an inhibitory effect on the cells, but the control with the vehicle also presented the same cytotoxic effect. In general, the effects obtained with the drugs were time and concentration dependent. Together, our results suggest a relevant role of FOXO3a in uterine smooth muscle tumors, in addition to presenting it as a potential target for specific therapy

<p>Stricter emission legislation for heavy trucks in combination with the customers demand on low fuel consumption has resulted in intensive technical development of engines and their control systems. To control all these new solutions it is desirable to have reliable models for important control variables. One of them is the air mass-flow, which is important when controlling the amount of recirculated exhaust gases in the EGR system and to make sure that the air to fuel ratio is correct in the cylinders. The purpose with this thesis was to use system identification theory to develop a model for the air mass-flow through the compressor. First linear black-box models were developed without any knowledge of the physics behind. The collected data was preprocessed to work in the modeling procedure and then models with one or more inputs where built according to the ARX model structure. To further improve the models performance, non-linear regressors was developed from physical relations for the air mass-flow and used to form grey-box models of the air mass-flow.In conclusion, the performance was evaluated through comparing the estimated air mass-flow from the best model with the estimate that an extended Kalman filter together with a physical model produced.</p> / <p>Hårdare utsläppskrav för tunga lastbilar i kombination med kundernas efterfrågan på låg bränsleförbrukning har resulterat i en intensiv utveckling av motorer och deras kontrollsystem. För att kunna styra alla dessa nya lösningar är det nödvändigt att ha tillförlitliga modeller över viktiga kontrollvariabler. En av dessa är luftmassflödet som är viktig när man ska kontrollera den mängd avgaser som återcirkuleras i EGR-systemet och för att se till att kvoten mellan luft och bränsle är korrekt i motorns cylindrar. Syftet med det här examensarbetet var att använda systemidentifiering för att ta fram en modell över luftmassflödet förbi kompressorn. Först togs linjära svartboxmodeller fram utan att ta med någon kunskap om den bakomliggande fysiken. Insamlade data förbehandlades för att passa in i modelleringsproceduren och efter det skapades i enlighet med ARX-modellstrukturen modeller med en eller flera insignaler. För att ytterligare förbättra modellernas prestanda togs icke-linjära regressorer fram med hjälp av fysikaliska relationer för luftmassflödet. Dessa användes sedan för att skapa gråboxmodeller av luftmassflödet. Avslutningsvis utvärderades prestandan genom att det estimerade luftmassflödet från den bästa modellen jämfördes med det estimat som ett utökat kalmanfilter tillsammans med fysikaliska ekvationer genererade.</p>

Neurons, astrocytes and oligodendrocytes of the central nervous system (CNS) arise from a common pool of multipotent neuroepithelial progenitor cells lining the walls of the neural tube. Initially, neuroepithelial cells undergo symmetric proliferative divisions, thereby expanding the progenitor pool and determining the size of brain compartments. At the onset of neurogenesis, a subset of progenitors switch to asymmetric or terminal symmetric neurogenic divisions. Maintenance of progenitor cell population throughout the period of neurogenesis is essential to generate the full diversity of neuronal cell types and proper histological pattern. However, the mechanisms responsible for the maintenance of progenitor cells proliferation are far from being fully understood. The family of Y-box proteins is involved in control of proliferation and transformation in various normal and pathological cellular systems, and therefore was considered as a candidate to exert such a function. Y-box proteins have a capacity to bind DNA and RNA, thereby controlling gene expression from transcription to translation. This study aimed to examine the expression of mouse Y-box protein 3 (MSY3) in the developing nervous system and elucidate its putative role in regulation of proliferation of progenitor cells. As presented in this work, the MSY3 protein in the embryonic CNS is expressed solely in progenitor cells and not neurons. Moreover, as shown by two independent approaches: morphologically, i.e. using immunofluorescence and confocal microscopy, and biochemically, MSY3 expression is downregulated concomitantly with the spatiotemporal progression of neurogenesis. Interestingly, in preliminary results it was shown that MSY3 is expressed in Dcx-positive transient amplifying precursors in germinal zones of the adult brain, and in EGF-dependent neurospheres. To evaluate whether MSY3 could regulate the neurogenesis, the levels of the MSY3 protein in the progenitors were acutely downregulated or elevated by electroporation of RNAi or MSY3 expression plasmids, respectively. Neither premature reduction of MSY3 in the neuroepithelium (E9.5-E11.5) nor prolonged expression at the developmental stage when this protein is endogenously downregulated (E10.5-14.5) did affect proliferation versus the cell cycle exit of progenitors. Moreover, in Notch1-deficient progenitors in the cerebellar anlage, which exhibit precocious differentiation, MSY3 was not prematurely downregulated, suggesting that MSY3 also is not an early marker of differentiation. Differential centrifugation, immunoprecipitation and polysomal analysis performed in this study revealed that the MSY3 protein in the developing embryo, as well as in Neuro-2A cells, is associated with RNA. On a sucrose density gradient MSY3 co-fractionates with ribosomes and actively translating polysomes, suggesting that it might have a role in regulation of translation. However, downregulation or overexpression of MSY3 in the Neuro-2A cell line did not affect global translation rates. Other researchers suggested that the MSY3 protein has the redundant function with Y-box protein 1 (YB-1). Accordingly, in our system the MSY3 protein could be co-immunoprecipitated with YB-1. Importantly, developmentally regulated expression of MSY3 is not a hallmark of general translation apparatus, as several other proteins involved in translation did not show similar downregulation. To summarise, this work showed that the MSY3 protein is a marker of proliferation of progenitor cells in the embryonic and adult brain, being absent from neurons. Discovery of the molecular mechanism by which MSY3 exerts its role in the cell could provide the link between the translational machinery and proliferation.